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Sample records for caspase-8s increased sensitivity

  1. Moire interferometry with increased sensitivity

    Science.gov (United States)

    Han, Bongtae; Post, Daniel

    The basic sensitivity of moire interferometry was increased beyond the previously conceived theoretical limit. This was accomplished by creating the virtual reference grating inside a refractive medium instead of air, thus shortening the wavelength of light. A very compact four-beam moire interferometer in a refractive medium was developed for microscopic viewing, which produced a basic sensitivity of 208 nm per fringe order, corresponding to moire with 4800 lines per mm. Its configuration made it inherently stable and relatively insensitive to environmental disturbances. An optical microscope was employed as the image recording system to obtain high spatial resolution. The method was demonstrated for deformation of a thick graphite/epoxy composite at the 0/90 deg ply interface.

  2. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth;

    2014-01-01

    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. We therefore investigated whether increased skeletal muscle capillarization increases insulin sensitivity....... Skeletal muscle specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist Prazosin to the drinking water of Sprague Dawley rats (n=33) while 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-week Prazosin treatment, which ensured......-body insulin sensitivity increased by ~24% and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]-Glucose disposal increased by ~30% concomitant with a ~20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake...

  3. Increase in the Array Television Camera Sensitivity

    Science.gov (United States)

    Shakhrukhanov, O. S.

    A simple adder circuit for successive television frames that enables to considerably increase the sensitivity of such radiation detectors is suggested by the example of array television camera QN902K.

  4. Interference comb-spectroscopy with increasing sensitivity

    Science.gov (United States)

    Pulkin, Sergey; Borisov, Evgenii; Balabas, Michail; Uvarova, Svetlana; Shevtzov, Vladimir; Kalinichev, Alexei; Shoev, Vladislav; Venediktov, Dmitrii; Venediktov, Vladimir

    2016-10-01

    The paper considers the use of holographic interferometer for hologram recording of the wide spectrum from the comb - generator of the femtosecond laser was applied for illuminating of Michelson interferometer with atomic vapor. The behavior of spectral interference fringes on the exit slit of spectrograph reflects the behavior of nonlinear refractive index. The method of holographic interferometry with increasing sensitivity using phase modulator was applied for digital hologram processing.

  5. Lamb waves increase sensitivity in nondestructive testing

    Science.gov (United States)

    Di Novi, R.

    1967-01-01

    Lamb waves improve sensitivity and resolution in the detection of small defects in thin plates and small diameter, thin-walled tubing. This improvement over shear waves applies to both longitudinal and transverse flaws in the specimens.

  6. Deep time evidence for climate sensitivity increase with warming

    Science.gov (United States)

    Shaffer, Gary; Huber, Matthew; Rondanelli, Roberto; Pepke Pedersen, Jens Olaf

    2016-06-01

    Future global warming from anthropogenic greenhouse gas emissions will depend on climate feedbacks, the effect of which is expressed by climate sensitivity, the warming for a doubling of atmospheric CO2 content. It is not clear how feedbacks, sensitivity, and temperature will evolve in our warming world, but past warming events may provide insight. Here we employ paleoreconstructions and new climate-carbon model simulations in a novel framework to explore a wide scenario range for the Paleocene-Eocene Thermal Maximum (PETM) carbon release and global warming event 55.8 Ma ago, a possible future warming analogue. We obtain constrained estimates of CO2 and climate sensitivity before and during the PETM and of the PETM carbon input amount and nature. Sensitivity increased from 3.3-5.6 to 3.7-6.5 K (Kelvin) into the PETM. When taken together with Last Glacial Maximum and modern estimates, this result indicates climate sensitivity increase with global warming.

  7. How to Determine the Increasing Returns Sensitivity of Your Industry?

    NARCIS (Netherlands)

    M.H. Klein (Martin); E. den Hartigh; H.R. Commandeur (Harry); F. Langerak (Fred)

    2004-01-01

    textabstractIncreasing returns means that self-reinforcing mechanisms are at work within firms and markets. These mechanisms come in four forms: scale effects, learning effects, network effects and social interaction effects. Some industries are more sensitive to increasing returns than others. It i

  8. Deep time evidence for climate sensitivity increase with warming

    DEFF Research Database (Denmark)

    Shaffer, Gary; Huber, Matthew; Rondanelli, Roberto;

    2016-01-01

    Future global warming from anthropogenic greenhouse gas emissions will depend on climate feedbacks, the effect of which is expressed by climate sensitivity, the warming for a doubling of atmospheric CO2 content. It is not clear how feedbacks, sensitivity, and temperature will evolve in our warming...... world, but past warming events may provide insight. Here we employ paleoreconstructions and new climate-carbon model simulations in a novel framework to explore a wide scenario range for the Paleocene-Eocene Thermal Maximum (PETM) carbon release and global warming event 55.8Ma ago, a possible future...... indicates climate sensitivity increase with global warming....

  9. Low ethanol consumption increases insulin sensitivity in Wistar rats

    Directory of Open Access Journals (Sweden)

    D.T. Furuya

    2003-01-01

    Full Text Available Several human studies suggest that light-to-moderate alcohol consumption is associated with enhanced insulin sensitivity, but these studies are not free of conflicting results. To determine if ethanol-enhanced insulin sensitivity could be demonstrated in an animal model, male Wistar rats were fed a standard chow diet and received drinking water without (control or with different ethanol concentrations (0.5, 1.5, 3, 4.5 and 7%, v/v for 4 weeks ad libitum. Then, an intravenous insulin tolerance test (IVITT was performed to determine insulin sensitivity. Among the ethanol groups, only the 3% ethanol group showed an increase in insulin sensitivity based on the increase of the plasma glucose disappearance rate in the IVITT (30%, P<0.05. In addition, an intravenous glucose tolerance test (IVGTT was performed in control and 3% ethanol animals. Insulin sensitivity was confirmed in 3% ethanol rats based on the reduction of insulin secretion in the IVGTT (35%, P<0.05, despite the same glucose profile. Additionally, the 3% ethanol treatment did not impair body weight gain or plasma aspartate aminotransferase and alanine aminotransferase activities. Thus, the present study established that 3% ethanol in the drinking water for 4 weeks in normal rats is a model of increased insulin sensitivity, which can be used for further investigations of the mechanisms involved.

  10. Orientation of llama antibodies strongly increases sensitivity of biosensors.

    Science.gov (United States)

    Trilling, Anke K; Hesselink, Thamara; van Houwelingen, Adèle; Cordewener, Jan H G; Jongsma, Maarten A; Schoffelen, Sanne; van Hest, Jan C M; Zuilhof, Han; Beekwilder, Jules

    2014-10-15

    Sensitivity of biosensors depends on the orientation of bio-receptors on the sensor surface. The objective of this study was to organize bio-receptors on surfaces in a way that their analyte binding site is exposed to the analyte solution. VHH proteins recognizing foot-and-mouth disease virus (FMDV) were used for making biosensors, and azides were introduced in the VHH to function as bioorthogonal reactive groups. The importance of the orientation of bio-receptors was addressed by comparing sensors with randomly oriented VHH (with multiple exposed azide groups) to sensors with uniformly oriented VHH (with only a single azide group). A surface plasmon resonance (SPR) chip exposing cyclooctyne was reacted to azide functionalized VHH domains, using click chemistry. Comparison between randomly and uniformly oriented bio-receptors showed up to 800-fold increase in biosensor sensitivity. This technique may increase the containment of infectious diseases such as FMDV as its strongly enhanced sensitivity may facilitate early diagnostics.

  11. Mindfulness meditation and relaxation training increases time sensitivity.

    Science.gov (United States)

    Droit-Volet, S; Fanget, M; Dambrun, M

    2015-01-01

    Two experiments examined the effect of mindfulness meditation and relaxation on time perception using a temporal bisection task. In Experiment 1, the participants performed a temporal task before and after exercises of mindfulness meditation or relaxation. In Experiment 2, the procedure was similar than that used in Experiment 1, except that the participants were trained to mediate or relax every day over a period of several weeks. The results showed that mindfulness meditation exercises increased sensitivity to time and lengthened perceived time. However, this temporal improvement with meditation exercises was primarily observed in the experienced meditators. Our results also showed the experienced meditators were less anxious than the novice participants, and that the sensitivity to time increased when the level of anxiety decreased. Our results were explained by the practice of mindfulness technique that had developed individuals' abilities in devoting more attention resources to temporal information processing.

  12. EPS8 inhibition increases cisplatin sensitivity in lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Lidija K Gorsic

    Full Text Available Cisplatin, a commonly used chemotherapeutic, is associated with ototoxicity, renal toxicity and neurotoxicity, thus identifying means to increase the therapeutic index of cisplatin may allow for improved outcomes. A SNP (rs4343077 within EPS8, discovered through a genome wide association study of cisplatin-induced cytotoxicity and apoptosis in lymphoblastoid cell lines (LCLs, provided impetus to further study this gene. The purpose of this work was to evaluate the role of EPS8 in cellular susceptibility to cisplatin in cancerous and non-cancerous cells. We used EPS8 RNA interference to determine the effect of decreased EPS8 expression on LCL and A549 lung cancer cell sensitivity to cisplatin. EPS8 knockdown in LCLs resulted in a 7.9% increase in cisplatin-induced survival (P = 1.98 × 10(-7 and an 8.7% decrease in apoptosis (P = 0.004 compared to control. In contrast, reduced EPS8 expression in lung cancer cells resulted in a 20.6% decrease in cisplatin-induced survival (P = 5.08 × 10(-5. We then investigated an EPS8 inhibitor, mithramycin A, as a potential agent to increase the therapeutic index of cisplatin. Mithramycin A decreased EPS8 expression in LCLs resulting in decreased cellular sensitivity to cisplatin as evidenced by lower caspase 3/7 activation following cisplatin treatment (42.7% ± 6.8% relative to control P = 0.0002. In 5 non-small-cell lung carcinoma (NSCLC cell lines, mithramycin A also resulted in decreased EPS8 expression. Adding mithramycin to 4 NSCLC cell lines and a bladder cancer cell line, resulted in increased sensitivity to cisplatin that was significantly more pronounced in tumor cell lines than in LCL lines (p<0.0001. An EGFR mutant NSCLC cell line (H1975 showed no significant change in sensitivity to cisplatin with the addition of mithramycin treatment. Therefore, an inhibitor of EPS8, such as mithramycin A, could improve cisplatin treatment by increasing sensitivity of tumor relative to normal cells.

  13. Current understanding of increased insulin sensitivity after exercise - emerging candidates

    DEFF Research Database (Denmark)

    Maarbjerg, Stine Just; Sylow, Lykke; Richter, Erik

    2011-01-01

    insulin sensitivity. It is believed that increased sarcolemmal content of the glucose transporter GLUT4 can explain the phenomenon to some extent. Surprisingly no improvement in the proximal insulin signaling pathway is observed at the level of the insulin receptor, IRS1, PI3K or Akt. Recently more distal...... signaling component in the insulin signaling pathway such as aPKC, Rac1, TBC1D4 and TBC1D1 have been described. These are all affected by both insulin and exercise which means that they are likely converging points in promoting GLUT4 translocation and therefore possible candidates for regulating insulin...... in signaling to GLUT4 translocation, factors influencing the trans-sarcolemmal glucose concentration gradient might also be important. With regard to the interstitial glucose concentration microvascular perfusion is particular relevant as correlative evidence supports a connection between insulin sensitivity...

  14. Increased Mutagen Sensitivity and DNA Damage in Pulmonary Arterial Hypertension

    Science.gov (United States)

    Federici, Chiara; Drake, Kylie M.; Rigelsky, Christina M.; McNelly, Lauren N.; Meade, Sirena L.; Comhair, Suzy A. A.; Erzurum, Serpil C.

    2015-01-01

    Rationale: Pulmonary arterial hypertension (PAH) is a serious lung condition characterized by vascular remodeling in the precapillary pulmonary arterioles. We and others have demonstrated chromosomal abnormalities and increased DNA damage in PAH lung vascular cells, but their timing and role in disease pathogenesis is unknown. Objectives: We hypothesized that if DNA damage predates PAH, it might be an intrinsic cell property that is present outside the diseased lung. Methods: We measured DNA damage, mutagen sensitivity, and reactive oxygen species (ROS) in lung and blood cells from patients with Group 1 PAH, their relatives, and unrelated control subjects. Measurements and Main Results: Baseline DNA damage was significantly elevated in PAH, both in pulmonary artery endothelial cells (P < 0.05) and peripheral blood mononuclear cells (PBMC) (P < 0.001). Remarkably, PBMC from unaffected relatives showed similar increases, indicating this is not related to PAH treatments. ROS levels were also higher (P < 0.01). DNA damage correlated with ROS production and was suppressed by antioxidants (P < 0.001). PBMC from patients and relatives also showed markedly increased sensitivity to two chemotherapeutic drugs, bleomycin and etoposide (P < 0.001). Results were consistent across idiopathic, heritable, and associated PAH groups. Conclusions: Levels of baseline and mutagen-induced DNA damage are intrinsically higher in PAH cells. Similar results in PBMC from unaffected relatives suggest this may be a genetically determined trait that predates disease onset and may act as a risk factor contributing to lung vascular remodeling following endothelial cell injury. Further studies are required to fully characterize mutagen sensitivity, which could have important implications for clinical management. PMID:25918951

  15. PARK2 patient neuroprogenitors show increased mitochondrial sensitivity to copper.

    Science.gov (United States)

    Aboud, Asad A; Tidball, Andrew M; Kumar, Kevin K; Neely, M Diana; Han, Bingying; Ess, Kevin C; Hong, Charles C; Erikson, Keith M; Hedera, Peter; Bowman, Aaron B

    2015-01-01

    Poorly-defined interactions between environmental and genetic risk factors underlie Parkinson's disease (PD) etiology. Here we tested the hypothesis that human stem cell derived forebrain neuroprogenitors from patients with known familial risk for early onset PD will exhibit enhanced sensitivity to PD environmental risk factors compared to healthy control subjects without a family history of PD. Two male siblings (SM and PM) with biallelic loss-of-function mutations in PARK2 were identified. Human induced pluripotent stem cells (hiPSCs) from SM, PM, and four control subjects with no known family histories of PD or related neurodegenerative diseases were utilized. We tested the hypothesis that hiPSC-derived neuroprogenitors from patients with PARK2 mutations would show heightened cell death, mitochondrial dysfunction, and reactive oxygen species generation compared to control cells as a result of exposure to heavy metals (PD environmental risk factors). We report that PARK2 mutant neuroprogenitors showed increased cytotoxicity with copper (Cu) and cadmium (Cd) exposure but not manganese (Mn) or methyl mercury (MeHg) relative to control neuroprogenitors. PARK2 mutant neuroprogenitors also showed a substantial increase in mitochondrial fragmentation, initial ROS generation, and loss of mitochondrial membrane potential following Cu exposure. Our data substantiate Cu exposure as an environmental risk factor for PD. Furthermore, we report a shift in the lowest observable effect level (LOEL) for greater sensitivity to Cu-dependent mitochondrial dysfunction in patients SM and PM relative to controls, correlating with their increased genetic risk for PD.

  16. Sensitivity Increases for the TITAN Decay Spectroscopy Program

    Directory of Open Access Journals (Sweden)

    Leach K.G.

    2015-01-01

    Full Text Available The TITAN facility at TRIUMF has recently initiated a program of performing decay spectroscopy measurements in an electron-beam ion-trap (EBIT. The unique environment of the EBIT provides backingfree storage of the radioactive ions, while guiding charged decay particles from the trap centre via the strong magnetic field. This measurement technique is able to provide a significant increase in detection sensitivity for photons which result from radioactive decay. A brief overview of this device is presented, along with methods of improving the signal-to-background ratio for photon detection by reducing Compton scattered events, and eliminating vibrational noise.

  17. Sensitivity Increases for the TITAN Decay Spectroscopy Program

    CERN Document Server

    Leach, K G; Grossheim, A; Andreoiu, C; Dilling, J; Frekers, D; Good, M; Seeraji, S

    2014-01-01

    The TITAN facility at TRIUMF has recently initiated a program of performing decay spectroscopy measurements in an electron-beam ion-trap (EBIT). The unique environment of the EBIT provides backing-free storage of the radioactive ions, while guiding charged decay particles from the trap centre via the strong magnetic field. This measurement technique is able to provide a significant increase in detection sensitivity for photons which result from radioactive decay. A brief overview of this device is presented, along with methods of improving the signal-to-background ratio for photon detection by reducing Compton scattered events, and eliminating vibrational noise.

  18. Increasing the sensitivity of a Shack-Hartmann sensor

    CERN Document Server

    Kasper, Markus; Hippler, Stefan; Davies, Ric; Glindemann, Andreas

    2016-01-01

    The Max-Planck institutes for astronomy (MPIA) and for extraterrestrial physics (MPE) run an adaptive optics (AO) system with a laser guide star at the 3.5 m telescope on Calar Alto, Spain. This system, called ALFA, produces now scientific results and works ex- cellent with natural guide stars (NGS) as faint as 13th magnitude in R-band. The ultimate goal however is to achieve similar performances with the laser guide star (LGS) which is faint and extended. We introduce the Shack-Hartmann wavefront sensor implemented in ALFA and present our efforts in increasing its sensitivity by using advanced centroiding and wavefront reconstruction algorithms.

  19. Increase in the Sensitivity and Selectivity of Semiconductor Gas Sensors

    Science.gov (United States)

    Muksunov, T. R.; Maksimova, N. K.; Sevast'yanov, E. Yu.; Shipilov, S. É.; Yakubov, V. P.

    2015-01-01

    Within the limits of a linear model based on processing of data of direct calibration measurements with semiconductor multisensors, a method of their calibration by standard levels of gas concentration is substantiated for its subsequent application for small concentration levels. On an example of data for nitrogen dioxide, the notion of the normalized surface density of the gas is introduced, and its relationship with the volume concentration is established. On this basis, the feasibility of increase in the sensitivity and selectivity of the multisensor system by several orders of magnitude compared with the existing instrumental methods is substantiated by imitational modeling using mathematical methods of modern algebra and regularization theory.

  20. Increased sensitivity to kindling in mice lacking TSP1.

    Science.gov (United States)

    Mendus, D; Rankin-Gee, E K; Mustapha, M; Porter, B E

    2015-10-01

    The development of a hyperexcitable neuronal network is thought to be a critical event in epilepsy. Thrombospondins (TSPs) regulate synaptogenesis by binding the neuronal α2δ subunit of the voltage-gated calcium channel. TSPs regulate synapse formation during development and in the mature brain following injury. It is unclear if TSPs are involved in hyperexcitability that contributes to the development of epilepsy. Here we explore the development of epilepsy using a pentylenetetrazole (PTZ) kindling model in mice lacking TSP1 and TSP2. Unexpectedly, we found increased sensitivity to PTZ kindling in mice lacking TSP1, while mice lacking TSP2 kindled similar to wild-type. We found that the increased seizure susceptibility in the TSP1 knockout (KO) mice was not due to a compensatory increase in TSP2 mRNA as TSP1/2 KO mice were sensitive to PTZ, similar to the TSP1 KO mice. Furthermore, there were similar levels of TGF-B signal activation during kindling in the TSP1 KO mice compared to wild-type. We observed decreased expression of voltage-dependent calcium channel subunit CACNA2D1 mRNA in TSP1, TSP2, and TSP1/2 KO mice. Decreased CACNA2D2 mRNA was only detected in mice that lacked TSP1 and α2δ-1/2 protein levels in the cortex were lower in the TSP 1/2 KO mice. CACNA2D2 knockout mice have spontaneous seizures and increased PTZ seizure susceptibility. Here we report similar findings, TSP1, and TSP1/2 KO mice have low levels of CACNA2D2 mRNA expression and α2δ-1/2 receptor level in the cortex, and are more susceptible to seizures. CACNA2D2 mutations in mice and humans can cause epilepsy. Our data suggest TSP1 in particular may control CACNA2D2 levels and could be a modifier of seizure susceptibility.

  1. Napping reverses increased pain sensitivity due to sleep restriction.

    Directory of Open Access Journals (Sweden)

    Brice Faraut

    Full Text Available To investigate pain sensitivity after sleep restriction and the restorative effect of napping.A strictly controlled randomized crossover study with continuous polysomnography monitoring was performed.Laboratory-based study.11 healthy male volunteers.Volunteers attended two three-day sessions: "sleep restriction" alone and "sleep restriction and nap". Each session involved a baseline night of normal sleep, a night of sleep deprivation and a night of free recovery sleep. Participants were allowed to sleep only from 02:00 to 04:00 during the sleep deprivation night. During the "sleep restriction and nap" session, volunteers took two 30-minute naps, one in the morning and one in the afternoon.Quantitative sensory testing was performed with heat, cold and pressure, at 10:00 and 16:00, on three areas: the supraspinatus, lower back and thigh. After sleep restriction, quantitative sensory testing revealed differential changes in pain stimuli thresholds, but not in thermal threshold detection: lower back heat pain threshold decreased, pressure pain threshold increased in the supraspinatus area and no change was observed for the thigh. Napping restored responses to heat pain stimuli in the lower back and to pressure stimuli in the supraspinatus area.Sleep restriction induces different types of hypersensitivity to pain stimuli in different body areas, consistent with multilevel mechanisms, these changes being reversed by napping. The napping restorative effect on pain thresholds result principally from effects on pain mechanisms, since it was independent of vigilance status.

  2. Glucose-deprivation increases thyroid cancer cells sensitivity to metformin.

    Science.gov (United States)

    Bikas, Athanasios; Jensen, Kirk; Patel, Aneeta; Costello, John; McDaniel, Dennis; Klubo-Gwiezdzinska, Joanna; Larin, Olexander; Hoperia, Victoria; Burman, Kenneth D; Boyle, Lisa; Wartofsky, Leonard; Vasko, Vasyl

    2015-12-01

    Metformin inhibits thyroid cancer cell growth. We sought to determine if variable glucose concentrations in medium alter the anti-cancer efficacy of metformin. Thyroid cancer cells (FTC133 and BCPAP) were cultured in high-glucose (20 mM) and low-glucose (5 mM) medium before treatment with metformin. Cell viability and apoptosis assays were performed. Expression of glycolytic genes was examined by real-time PCR, western blot, and immunostaining. Metformin inhibited cellular proliferation in high-glucose medium and induced cell death in low-glucose medium. In low-, but not in high-glucose medium, metformin induced endoplasmic reticulum stress, autophagy, and oncosis. At micromolar concentrations, metformin induced phosphorylation of AMP-activated protein kinase and blocked p-pS6 in low-glucose medium. Metformin increased the rate of glucose consumption from the medium and prompted medium acidification. Medium supplementation with glucose reversed metformin-inducible morphological changes. Treatment with an inhibitor of glycolysis (2-deoxy-d-glucose (2-DG)) increased thyroid cancer cell sensitivity to metformin. The combination of 2-DG with metformin led to cell death. Thyroid cancer cell lines were characterized by over-expression of glycolytic genes, and metformin decreased the protein level of pyruvate kinase muscle 2 (PKM2). PKM2 expression was detected in recurrent thyroid cancer tissue samples. In conclusion, we have demonstrated that the glucose concentration in the cellular milieu is a factor modulating metformin's anti-cancer activity. These data suggest that the combination of metformin with inhibitors of glycolysis could represent a new strategy for the treatment of thyroid cancer.

  3. Deep time evidence for climate sensitivity increase with warming

    DEFF Research Database (Denmark)

    Shaffer, Gary; Huber, Matthew; Rondanelli, Roberto;

    2016-01-01

    Future global warming from anthropogenic greenhouse gas emissions will depend on climate feedbacks, the effect of which is expressed by climate sensitivity, the warming for a doubling of atmospheric CO2 content. It is not clear how feedbacks, sensitivity, and temperature will evolve in our warmin...

  4. Increased risk of horse sensitization in southwestern Iranian horse riders

    Directory of Open Access Journals (Sweden)

    Mozhgan Moghtaderi

    2015-10-01

    Full Text Available Objectives: The aim of this study has been to investigate the frequency of sensitization to horse allergens and clinical symptoms in horse riders. Material and Methods: A total of 42 horse riders and 50 healthy individuals were examined by means of skin prick tests for a panel of horse and common animal allergens, and pulmonary function tests were done by spirometry. Results: The rate of sensitization to horse allergens was 31% as proven by the skin prick test in horse riders whereas horse sensitization was not seen in the control group. Occupational allergy symptoms were reported by 19 horse riders. Two horse riders with no history of clinical symptoms showed positive skin reactions to horse allergens. Conclusions: To decrease the high risk of occupational sensitization among horse riders, workplace conditions should be improved to reduce the load of airborne horse allergens.

  5. Increased sensitivity to climate change in disturbed ecosystems

    DEFF Research Database (Denmark)

    Kroël-Dulay, György; Ransijn, Johannes; Schmidt, Inger Kappel;

    2015-01-01

    , with recently disturbed sites responding to treatments. Furthermore, most of these responses are not rapid (2-5 years) but emerge over a longer term (7-14 years). These results suggest that successional state influences the sensitivity of ecosystems to climate change, and that ecosystems recovering from...... disturbances may be sensitive to even modest climatic changes. A research bias towards undisturbed ecosystems might thus lead to an underestimation of the impacts of climate change....

  6. Natural dyes as sensitizers to increase the efficiency in sensitized solar cells

    Science.gov (United States)

    Cerda, Bayron; Sivakumar, R.; Paulraj, M.

    2016-05-01

    A dye-sensitized solar cell (DSSC) is a sandwich type solar cell consisting of a photoelectrode, a counter electrode and a liquid electrolyte. The photo electrode comprises of a titanium dioxide semiconducting thin film grown over a glass substrate which in-turn has a transparent thin conducting layer of tin oxide film doped with fluorine (FTO) coated over it. The aim of this work is to develop photoelectrodes with different dyes to increase the efficiency of this type of solar cells. Dyes obtained from fresh sources of maqui, black myrtle, spinach and a dye mixture of spinach and spinach-maqui-myrtle were used. The technique used for the extraction of the dyes was maceration for one day, in methanol. Colourants and photoelectrodes were studied using, UV-vis spectrophotometer for their spectral properties. Their photovoltaic properties such as efficiency, fill factor, open circuit voltage and short circuit current were studied using a solar simulator and source meter unit.

  7. Increased risk of horse sensitization in southwestern Iranian horse riders

    OpenAIRE

    Mozhgan Moghtaderi; Shirin Farjadian; Zeynab Hosseini; Alireza Raayat

    2015-01-01

    Objectives: The aim of this study has been to investigate the frequency of sensitization to horse allergens and clinical symptoms in horse riders. Material and Methods: A total of 42 horse riders and 50 healthy individuals were examined by means of skin prick tests for a panel of horse and common animal allergens, and pulmonary function tests were done by spirometry. Results: The rate of sensitization to horse allergens was 31% as proven by the skin prick test in horse riders whereas horse se...

  8. Napping Reverses Increased Pain Sensitivity Due to Sleep Restriction

    OpenAIRE

    Brice Faraut; Damien Léger; Terkia Medkour; Alexandre Dubois; Virginie Bayon; Mounir Chennaoui; Serge Perrot

    2015-01-01

    Study Objective To investigate pain sensitivity after sleep restriction and the restorative effect of napping. Design A strictly controlled randomized crossover study with continuous polysomnography monitoring was performed. Setting Laboratory-based study. Participants 11 healthy male volunteers. Interventions Volunteers attended two three-day sessions: “sleep restriction” alone and “sleep restriction and nap”. Each session involved a baseline night of normal sleep, a night of sleep deprivati...

  9. Increasing the Sensitivity of the Michelson Interferometer through Multiple Reflection

    Science.gov (United States)

    Youn, Woonghee

    Michelson interferometry has been one of the most famous and popular optical interference system for analyzing optical components and measuring optical metrology properties. Typical Michelson interferometer can measure object displacement with wavefront shapes to one half of the laser wavelength. As testing components and devices size reduce to micro and nano dimension, Michelson interferometer sensitivity is not suitable. The purpose of this study is to design and develop the Michelson interferometer using the concept of multiple reflections. This thesis proposes a new and novel design for a multiple reflection interferometer, where the number of reflections does not affect the quality of the interference. Theoretically we show that more than 1000 reflections can be achieved. Experimental results of greater than 100 reflections are presented in this thesis.

  10. Increasing the sensitivity of Kepler to Earth-like exoplanets

    Science.gov (United States)

    Foreman-Mackey, Daniel; Hogg, David W.; Schölkopf, Bernhard; Wang, Dun

    2015-01-01

    Many transiting exoplanets have been discovered using photometry from the Kepler mission but the results are still very incomplete in some of the most interesting parts of parameter space: small planetary radius and long orbital period. We have developed a method for detecting transiting exoplanet signals in stellar light curves that is more sensitive to small planets on long orbits than previously published procedures. It is standard practice to start by "de-trending" the light curves—by filtering—to remove the instrumental systematics and stellar variability from the time series. Instead, we build an flexible model for these effects using a Gaussian Process. We use as inputs to the Gaussian Process not just time but also the light curves of dozens of other stars. This exploits the causal structure of the problem: permitting the noise model to capture spacecraft-induced covariability. Since we know a priori that the other stars are causally unrelated to the star of interest, any information that they share must be due to systematics. A key motivation for our work is that any filtering—no matter how robust—reduces the amplitude of the signals of interest. By marginalizing over the stellar and instrumental variability while simultaneously fitting for the transits, we maintain sensitivity to transit signals and reduce contamination. We apply our method to light curves from the Kepler mission. Using synthetic transits generated by realistic planetary systems injected into raw aperture photometry from the pipeline, we determine the detection efficiency of our method and train a supervised classification algorithm to weed out false signals. Our pipeline returns all of the ingredients needed for studies of exoplanet populations: a catalog of planet candidates, posterior samples for the physical parameters of these planets and their host stars, and an empirical measurement of the detection efficiency as a function of all of these parameters.

  11. Deep time evidence for climate sensitivity increase with warming:Climate Sensitivity Rise With Warming

    OpenAIRE

    Shaffer, Gary; Huber, Matthew; Rondanelli, Roberto; Pedersen, Jens Olaf Pepke

    2016-01-01

    Future global warming from anthropogenic greenhouse gas emissions will depend on climate feedbacks, the effect of which is expressed by climate sensitivity, the warming for a doubling of atmospheric CO2 content. It is not clear how feedbacks, sensitivity, and temperature will evolve in our warming world, but past warming events may provide insight. Here we employ paleoreconstructions and new climate-carbon model simulations in a novel framework to explore a wide scenario range for the Paleoce...

  12. Mice lacking neuropeptide Y show increased sensitivity to cocaine

    DEFF Research Database (Denmark)

    Sørensen, Gunnar; Woldbye, David Paul Drucker

    2012-01-01

    There is increasing data implicating neuropeptide Y (NPY) in the neurobiology of addiction. This study explored the possible role of NPY in cocaine-induced behavior using NPY knockout mice. The transgenic mice showed a hypersensitive response to cocaine in three animal models of cocaine addiction...

  13. Large diurnal temperature range increases bird sensitivity to climate change

    NARCIS (Netherlands)

    Briga, Michael; Verhulst, Simon

    2015-01-01

    Climate variability is changing on multiple temporal scales, and little is known of the consequences of increases in short-term variability, particularly in endotherms. Using mortality data with high temporal resolution of zebra finches living in large outdoor aviaries (5 years, 359.220 bird-days),

  14. Quantifying the increasing sensitivity of power systems to climate variability

    Science.gov (United States)

    Bloomfield, H. C.; Brayshaw, D. J.; Shaffrey, L. C.; Coker, P. J.; Thornton, H. E.

    2016-12-01

    Large quantities of weather-dependent renewable energy generation are expected in power systems under climate change mitigation policies, yet little attention has been given to the impact of long term climate variability. By combining state-of-the-art multi-decadal meteorological records with a parsimonious representation of a power system, this study characterises the impact of year-to-year climate variability on multiple aspects of the power system of Great Britain (including coal, gas and nuclear generation), demonstrating why multi-decadal approaches are necessary. All aspects of the example system are impacted by inter-annual climate variability, with the impacts being most pronounced for baseload generation. The impacts of inter-annual climate variability increase in a 2025 wind-power scenario, with a 4-fold increase in the inter-annual range of operating hours for baseload such as nuclear. The impacts on peak load and peaking-plant are comparably small. Less than 10 years of power supply and demand data are shown to be insufficient for providing robust power system planning guidance. This suggests renewable integration studies—widely used in policy, investment and system design—should adopt a more robust approach to climate characterisation.

  15. Increased sensitivity to interferon-alpha in psoriatic T cells

    DEFF Research Database (Denmark)

    Eriksen, Karsten Wessel; Lovato, Paola; Skov, Lone

    2005-01-01

    disease characterized by CD8(+)-infiltrating T cells. In this study, we therefore investigate IFN-alpha signaling in T cells isolated from involved skin of psoriatic patients. We show that psoriatic T cells have increased and prolonged responses to IFN-alpha, on the level of signal transducers......Psoriasis is a chronic inflammatory skin disease characterized by abnormal epidermal proliferation. Several studies have shown that skin-infiltrating activated T cells and cytokines play a pivotal role during the initiation and maintenance of the disease. Interferon (IFN)-alpha plays an important...... role in host defense against infections, but recent data have also implicated IFN-alpha in psoriasis. Thus, IFN-alpha induces or aggravates psoriasis in some patients, and mice lacking a transcriptional attenuator of IFN-alpha/beta signaling spontaneously develop a psoriasis-like inflammatory skin...

  16. Bleaching induced tooth sensitivity: do the existing enamel craze lines increase sensitivity? A clinical study.

    Science.gov (United States)

    Özcan, Mutlu; Abdin, Sam; Sipahi, Cumhur

    2014-07-01

    The aim of this clinical study was to evaluate whether or not an association exists between the presence of enamel craze lines and the prevalence of tooth sensitivity (TS) after in-office bleaching. Subjects that met the inclusion criteria (N = 23) were screened to detect the existence of enamel craze lines. In total, 460 teeth were subjected to bleaching where 49% of them presented enamel craze lines. After bleaching (15% hydrogen peroxide), the subjects were asked to rate the level of TS by answering a self-administered questionnaire. The majority of subjects (91%) experienced TS at the first day of bleaching. The TS prevalence decreased gradually to 22% at second day, to 17% at third day, and to 9% at fourth day. After the fourth day, no subject reported TS. While 15% of teeth with craze lines presented TS, 11% of teeth with no craze lines also showed TS. A positive but weak correlation (r = 0.214) was found between the existence of enamel craze lines and TS. In this clinical study, higher incidence of TS was found with the use of 15% hydrogen peroxide bleaching agent compared to the previous studies. Patients who would undergo in-office bleaching should be informed that tooth sensitivity is a very often side effect but it may disappear within 1 week.

  17. A novel concept for increasing the peak sensitivity of LIGO by detuning the arm cavities

    CERN Document Server

    Hild, S

    2007-01-01

    We introduce a concept that uses detuned arm cavities to increase the shot noise limited sensitivity of LIGO without increasing the light power inside the arm cavities. Numerical simulations show an increased sensitivity between 125 and 400 Hz, with a maximal improvement of about 80% around 225 Hz, while the sensitivity above 400Hz is decreased. Furthermore our concept is found to give a sensitivity similar to that of a conventional RSE configuration with a Signal-Recycling mirror of moderate reflectivity. In the near future detuned arm cavities might be a beneficial alternative to RSE, due the potentially less hardware intensive implementation of the proposed concept.

  18. Increased light harvesting in dye-sensitized solar cells with energy relay dyes

    KAUST Repository

    Hardin, Brian E.

    2009-06-21

    Conventional dye-sensitized solar cells have excellent charge collection efficiencies, high open-circuit voltages and good fill factors. However, dye-sensitized solar cells do not completely absorb all of the photons from the visible and near-infrared domain and consequently have lower short-circuit photocurrent densities than inorganic photovoltaic devices. Here, we present a new design where high-energy photons are absorbed by highly photoluminescent chromophores unattached to the titania and undergo Förster resonant energy transfer to the sensitizing dye. This novel architecture allows for broader spectral absorption, an increase in dye loading, and relaxes the design requirements for the sensitizing dye. We demonstrate a 26% increase in power conversion efficiency when using an energy relay dye (PTCDI) with an organic sensitizing dye (TT1). We estimate the average excitation transfer efficiency in this system to be at least 47%. This system offers a viable pathway to develop more efficient dye-sensitized solar cells.

  19. Children Increase Their Sensitivity to a Speaker's Nonlinguistic Cues Following a Communicative Breakdown

    Science.gov (United States)

    Yow, W. Quin; Markman, Ellen M.

    2016-01-01

    Bilingual children regularly face communicative challenges when speakers switch languages. To cope with such challenges, children may attempt to discern a speaker's communicative intent, thereby heightening their sensitivity to nonverbal communicative cues. Two studies examined whether such communication breakdowns increase sensitivity to…

  20. Ethosome formulations of known contact allergens can increase their sensitizing capacity.

    Science.gov (United States)

    Madsen, Jacob Torp; Vogel, Stefan; Karlberg, Ann-Therese; Simonsson, Carl; Johansen, Jeanne D; Andersen, Klaus E

    2010-07-01

    Vesicular systems, such as liposomes and ethosomes, are used in cosmetic and pharmaceutical products to encapsulate ingredients, to protect ingredients from degradation, to increase bioavailability, and to improve cosmetic performance. Some reports have suggested that formulation of cosmetic ingredients in vesicular carrier systems may increase their contact allergy elicitation potential in humans. However, no sensitization studies have been published. We formulated two model contact allergens (isoeugenol and dinitrochlorobenzene) in ethosomes and investigated the sensitization response using a modified local lymph node assay (LLNA). The results were compared with those for the same allergens in similar concentrations and vehicles without ethosomes. Both allergens encapsulated in 200-300 nm ethosomes showed increased sensitizing potency in the murine assay compared with the allergens in solution without ethosomes. Empty ethosomes were non-sensitizing according to LLNA. The clinical implications are so far uncertain, but increased allergenicity from ethosome-encapsulated topical product ingredients cannot be excluded.

  1. Passive gravitational sedimentation of peripheral blood increases the sensitivity of microscopic detection of malaria

    Institute of Scientific and Technical Information of China (English)

    Richard Davis; Trenden Flanigan; Eric Wilson

    2013-01-01

    Objective: To determine if passive gravitational sedimentation of blood samples, followed by buffy coat thin smear preparation could increase the sensitivity of malaria diagnosis when compared to conventional thin smear preparation without the additional cost of centrifuges or molecular diagnostics. Methods: Blood samples were collected from 205 patients. Each patient sample was analyzed using all three methods of sample preparation. Results: Buffy coat analysis of centrifuged blood samples greatly increased the sensitivity of malaria diagnosis when compared to standard thin smear techniques. Sensitivity between mechanically centrifuged samples and gravitationally sedimented samples showed equal improvement in sensitivity when compared to standard thin smear preparation. Conclusions: Passive gravitational sedimentation of red blood cells followed by buffy coat analysis dramatically improves the sensitivity of malaria diagnosis without the additional costs associated with centrifugation.

  2. Increasing the sensitivity for tilt measurement using a cyclic interferometer with multiple reflections

    Science.gov (United States)

    Pretheesh Kumar, Valiyaparambil Chacko; Joenathan, Charles; Ganesan, Angarai; Somasundram, Umapathy

    2016-08-01

    Measurement of tilt plays an important role in metrological applications and consequently, several methods have been proposed in the recent past. Classical interferometric methods can measure angles with high accuracy but are easily susceptible to external turbulences. We propose to use a cyclic interferometer to measure tilt in which the sensitivity to tilt measurement is double when compared with that of the classical Michelson interferometer. Since the counter propagating beams travel identical paths, the interferometer is insensitive to external vibrations and turbulence and thus can be used under harsh environmental conditions. The novelty in the technique lies in creating multiple reflections in the tilt mirror to enhance the measurement accuracy by the way of increasing the sensitivity. This paper presents the basics of the interferometer and experimental results to quantify the increase in sensitivity. By increasing the number of reflections, it is shown that sensitivity can be further improved to measure tilt angles below 5 μrad.

  3. Contact sensitizers specifically increase MHC class II expression on murine immature dendritic cells.

    Science.gov (United States)

    Herouet, C; Cottin, M; LeClaire, J; Enk, A; Rousset, F

    2000-01-01

    Contact sensitivity is a T-cell-mediated immune disease that can occur when low-molecular-weight chemicals penetrate the skin. In vivo topical application of chemical sensitizers results in morphological modification of Langerhans cells (LC). Moreover, within 18 h, LC increase their major histocompatibility complex (MHC) class II antigens expression and migrate to lymph nodes where they present the sensitizer to T lymphocytes. We wanted to determine if such an effect could also be observed in vitro. However, because of the high genetic diversity encountered in humans, assays were performed with dendritic cells (DC) obtained from a Balb/c mouse strain. The capacity of a strong sensitizer, DNBS (2,4-dinitrobenzene sulfonic acid), to modulate the phenotype of bone marrow-derived DC in vitro, was investigated. A specific and marked increase of MHC class II molecules expression was observed within 18 h. To eliminate the use of animals in sensitization studies, the XS52 DC line was tested at an immature stage. A 30-min contact with the strong sensitizers DNBS and oxazolone, or the moderate mercaptobenzothiazole, resulted in upregulation of MHC class II molecules expression, analyzed after 18-h incubation. This effect was not observed with irritants (dimethyl sulfoxide and sodium lauryl sulfate) nor with a neutral molecule (sodium chloride). These data suggested the possibility of developing an in vitro model for the identification of the sensitizing potential of chemicals, using a constant and non animal-consuming material.

  4. Prior AICAR stimulation increases insulin sensitivity in mouse skeletal muscle in an AMPK-dependent manner

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus; Treebak, Jonas T; Fentz, Joachim;

    2015-01-01

    An acute bout of exercise increases glucose uptake in skeletal muscle by an insulin-independent mechanism. In the period after exercise, insulin sensitivity to increased glucose uptake is enhanced. The molecular mechanisms underpinning this phenomenon are poorly understood but appear to involve a...

  5. Niacin Skin Sensitivity Is Increased in Adolescents at Ultra-High Risk for Psychosis.

    Directory of Open Access Journals (Sweden)

    Gregor E Berger

    Full Text Available Most studies provide evidence that the skin flush response to nicotinic acid (niacin stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR phase of psychotic disorders.We compared visual ratings of niacin sensitivity between adolescents at UHR for psychosis according to the one year transition outcome (UHR-T n = 11; UHR-NT n = 55 with healthy controls (HC n = 25 and first episode schizophrenia patients (FEP n = 25 treated with atypical antipsychotics.Contrary to our hypothesis niacin sensitivity of the entire UHR group was not attenuated, but significantly increased compared to the HC group, whereas no difference could be found between the UHR-T and UHR-NT groups. As expected, niacin sensitivity of FEP was attenuated compared to HC group. In UHR individuals niacin sensitivity was inversely correlated with omega-6 and -9 fatty acids (FA, but positively correlated with phospholipase A2 (inPLA2 activity, a marker of membrane lipid repair/remodelling.Increased niacin sensitivity in UHR states likely indicates an impaired balance of eicosanoids and omega-6/-9 FA at a membrane level. Our findings suggest that the emergence of psychosis is associated with an increased mobilisation of eicosanoids prior to the transition to psychosis possibly reflecting a "pro-inflammatory state", whereas thereafter eicosanoid mobilisation seems to be attenuated. Potential treatment implications for the UHR state should be further investigated.

  6. Inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer

    Institute of Scientific and Technical Information of China (English)

    Zhao Li; Ma Yongjie; Gu Feng; Fu Li

    2014-01-01

    Background Paclitaxel (PAC) is the first-line chemotherapy drug for most breast cancer patients,but clinical studies showed that some breast cancer patients were insensitive to PAC,which led to chemotherapy failure.It was reported that Notch1 signaling participated in drug resistance of breast cancer.Here,we show whether Notch1 expression is related to PAC sensitivity of breast cancer.Methods We employed Notch1 siRNA and Notch1 inhibitor,N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT),to down regulate Notch1 expression in human breast cancer cells MDA-MB-231,and detected the inhibition effect by Western blotting and reverse trans cription-polymerase chain reaction,respectively.After 24 hours exposure to different concentration of PAC (0,1,5,10,15,20,and 25 μg/ml),the viability of the control group and experimental group cells was tested by MTT.We also examined the expression of Notch1 in PAC sensitive and nonsensitive breast cancer patients,respectively by immunohistochemistry (IHC).The PAC sensitivity of breast cancer patients were identified by collagen gel droplet embedded culture-drug sensitivity test (CD-DST).Results Down regulation of Notch1 expression by Notch1siRNA interference or Notch1 inhibitor increased the PAC sensitivity in MDA-MB-231 cells (P <0.05).Also,the expression of Notch1 in PAC sensitive patients was much lower than that of PAC non-sensitive patients (P <0.01).Conclusion Notch1 expression has an effect on PAC sensitivity in breast cancer patients,and the inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer.

  7. Co-treatment of Salinomycin Sensitizes AZD5363-treated Cancer Cells Through Increased Apoptosis.

    Science.gov (United States)

    Choi, Ae-Ran; Jung, Myung-Ji; Kim, Ju-Hwa; Yoon, Sungpil

    2015-09-01

    AZD5363, an inhibitor of protein kinase B (AKT), is currently in clinical trials assessing the potential of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. The purpose of the present study was to identify conditions that increase the sensitivity of cancer cells to AZD5363. Microscopic examination revealed that treatment of cancer cells with a low concentration of salinomycin reduced cellular growth of AZD5363-treated breast cancer cells. Furthermore, fluorescence-activated cell sorting (FACS) analysis, Hoechst staining, and annexin V staining revealed that co-treatment with salinomycin sensitizes AZD5363-treated cancer cells via increased apoptosis with S-phase arrest. These results suggest that salinomycin can be applied to increase treatment efficacy for AZD5363-treated cancer cells. Our findings may contribute to improving the efficacy of the development of AZD5363-based sensitization therapies for patients with cancer.

  8. Continuous-flow ATP amplification system for increasing the sensitivity of quantitative bioluminescence assay.

    Science.gov (United States)

    Satoh, Tetsuya; Shinoda, Yasuharu; Alexandrov, Maxym; Kuroda, Akio; Murakami, Yuji

    2008-08-01

    We constructed a novel ATP amplification reactor using a continuous-flow system, and this allowed us to increase the sensitivity of a quantitative bioluminescence assay by controlling the number of ATP amplification cycles. We previously developed a bioluminescence assay coupled with ATP amplification using a batch system. However, it was difficult to control the number of amplification cycles. In this study, ATP amplification was performed using a continuous-flow system, and significant linear correlations between amplified luminescence and initial ATP concentration were observed. When performing four cycles of continuous-flow ATP amplification, the gradient of amplification was 1.87(N). Whereas the lower quantifiable level was 500 pM without amplification, values as low as 50 pM ATP could be measured after amplification. The sensitivity thus increased 10-fold, with further improvements expected with additional amplification cycles. The continuous-flow system thus effectively increased the sensitivity of the quantitative bioluminescence assay.

  9. Ethosome formulations of known contact allergens can increase their sensitizing capacity

    DEFF Research Database (Denmark)

    Madsen, Jakob Torp; Vogel, Stefan; Karlberg, Ann-Therese;

    2010-01-01

    Vesicular systems, such as liposomes and ethosomes, are used in cosmetic and pharmaceutical products to encapsulate ingredients, to protect ingredients from degradation, to increase bioavailability, and to improve cosmetic performance. Some reports have suggested that formulation of cosmetic...... ingredients in vesicular carrier systems may increase their contact allergy elicitation potential in humans. However, no sensitization studies have been published. We formulated two model contact allergens (isoeugenol and dinitrochlorobenzene) in ethosomes and investigated the sensitization response using...... a modified local lymph node assay (LLNA). The results were compared with those for the same allergens in similar concentrations and vehicles without ethosomes. Both allergens encapsulated in 200-300 nm ethosomes showed increased sensitizing potency in the murine assay compared with the allergens in solution...

  10. Increased sensitivity to a nondepolarizing muscle relaxant in a patient with acquired neuromyotonia.

    Science.gov (United States)

    Ginsburg, Greg; Forde, Ryan; Martyn, Jeevendra A J; Eikermann, Matthias

    2009-07-01

    Neuromyotonia is a disorder of hyperexcitability of the peripheral nerve. It has electromyographic features of spontaneous, continuous, irregularly occurring doublets, or multiplets of motor unit potential discharges. Neuromyotonia is characterized by both myokymic and neuromyotonic discharges. To our knowledge, this is the first report in the literature to assess the sensitivity of skeletal muscle to a nondepolarizing muscle relaxant drug, rocuronium, in a woman with acquired neuromyotonia. She had a past medical history notable for prolonged postoperative paralysis following anesthesia. The patient showed increased sensitivity to the neuromuscular effects of rocuronium. This increase in sensitivity may be explained by downregulation of acetylcholine receptors in response to chronic high agonist (acetylcholine) concentrations. If patients with neuromyotonia receive anesthesia, we recommend that smaller doses of a nondepolarizing muscle relaxant be administered, accompanied by monitoring of neuromuscular function, so as to provide optimal muscle relaxation while avoiding overdose and prolonged postoperative recovery.

  11. Aerobic exercise increases peripheral and hepatic insulin sensitivity in sedentary adolescents

    Science.gov (United States)

    The increasing prevalence of obesity and its consequences is a serious public health concern. The present study was undertaken to determine whether a controlled aerobic exercise program (without weight loss) improves insulin sensitivity and glucose metabolism in sedentary adolescents. Twenty nine p...

  12. Moderate alcohol consumption increases insulin sensitivity and ADIPOQ expression in postmenopausal women: A randomised, crossover trial

    NARCIS (Netherlands)

    Joosten, M.M.; Beulens, J.W.J.; Kersten, S.; Hendriks, H.F.J.

    2008-01-01

    Aims/hypothesis: To determine whether 6 weeks of daily, moderate alcohol consumption increases expression of the gene encoding adiponectin (ADIPOQ) and plasma levels of the protein, and improves insulin sensitivity in postmenopausal women. Methods: In a randomised, open-label, crossover trial conduc

  13. Ageing increases the sensitivity of neem (Azadirachta indica) seeds to imbibitional stress

    NARCIS (Netherlands)

    Neya, O.; Golovina, E.A.; Nijsse, J.; Hoekstra, F.A.

    2004-01-01

    Imbibitional stress was imposed on neem (Azadirachta indica) seeds by letting them soak for 1 h in water at unfavourable, low temperatures before further incubation at 30degreesC. Sensitivity to low imbibition temperatures increased with a decrease in seed moisture content (MC). To investigate a pos

  14. Increased sensitivity in fiber-based spectroscopy using carbon-coated fiber.

    Science.gov (United States)

    Sudirman, Aziza; Norin, Lars; Margulis, Walter

    2012-12-17

    Carbon-coated optical fibers are used here for reducing the luminescence background created by the primary-coating and thus increase the sensitivity of fiber-based spectroscopy systems. The 2-3 orders of magnitude signal-to-noise ratio improvement with standard telecom fibers is sufficient to allow for their use as Raman probes in the identification of organic solvents.

  15. Ethosome formulations of known contact allergens can increase their sensitizing capacity

    DEFF Research Database (Denmark)

    Madsen, Jacob Torp; Vogel, Stefan; Karlberg, Ann-Therese;

    2010-01-01

    a modified local lymph node assay (LLNA). The results were compared with those for the same allergens in similar concentrations and vehicles without ethosomes. Both allergens encapsulated in 200-300 nm ethosomes showed increased sensitizing potency in the murine assay compared with the allergens in solution...

  16. Increased calcium/calmodulin-dependent protein kinase II activity by morphine-sensitization in rat hippocampus.

    Science.gov (United States)

    Kadivar, Mehdi; Farahmandfar, Maryam; Ranjbar, Faezeh Esmaeli; Zarrindast, Mohammad-Reza

    2014-07-01

    Repeated exposure to drugs of abuse, such as morphine, elicits a progressive enhancement of drug-induced behavioral responses, a phenomenon termed behavioral sensitization. These changes in behavior may reflect long-lasting changes in some of the important molecules involved in memory processing such as calcium/calmodulin-dependent protein kinase II (CaMKII). In the present study, we investigated the effect of morphine sensitization on mRNA expression of α and β isoforms and activity of CaMKII in the hippocampus of male rats. Animals were treated for 3 days with saline or morphine (20mg/kg) and following a washout period of 5 days, a challenge dose of morphine (5mg/kg) were administered. The results indicate that morphine administration in pre-treated animals produces behavioral sensitization, as determined by significant increase in locomotion and oral stereotypy behavior. In addition, repeated morphine treatment increased mRNA expression of both α and β isoforms of CaMKII in the hippocampus. The present study also showed that induction of morphine sensitization significantly increased both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II in the rat hippocampus. However, acute administration of morphine (5mg/kg) did not alter either α and β CaMKII mRNA expression or CaMKII activity in the hippocampus. The stimulation effects of morphine sensitization on mRNA expression and activity of CaMKII were completely abolished by administration of naloxone, 30min prior to s.c. injections of morphine (20mg/kg/day×3 days). Our data demonstrated that induction of morphine sensitization could effectively modulate the activity and the mRNA expression of CaMKII in the hippocampus and this effect of morphine was exerted by the activation of opioid receptors.

  17. Increasing trend of sensitization to Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI).

    Science.gov (United States)

    Scherrer, Maria Antonieta Rios; Rocha, Vanessa Barreto

    2014-01-01

    Recent reports have shown increased sensitization to Methylchloroisothiazolinone/methylisothiazolinone. We report a retrospective study conducted at the Hospital das Clínicas--UFMG, based on the results of patch tests with the Brazilian standard series, performed on referred patients. The positive results in 359 patients from November 2009 to October 2012 were analyzed and compared with the previous data collected from March 2006 to October 2009 (447 patients). The data showed 11.14% sensitization to Methylchloroisothiazolinone/ methylisothiazolinone during 2009-2012, contrasting with the previous period (3.35%). A positive association was found between its positivity and the period of 2009-2012.

  18. Increasing trend of sensitization to Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI)*

    Science.gov (United States)

    Scherrer, Maria Antonieta Rios; Rocha, Vanessa Barreto

    2014-01-01

    Recent reports have shown increased sensitization to Methylchloroisothiazolinone/methylisothiazolinone. We report a retrospective study conducted at the Hospital das Clínicas - UFMG, based on the results of patch tests with the Brazilian standard series, performed on referred patients. The positive results in 359 patients from November 2009 to October 2012 were analyzed and compared with the previous data collected from March 2006 to October 2009 (447 patients). The data showed 11.14% sensitization to Methylchloroisothiazolinone/ methylisothiazolinone during 2009-2012, contrasting with the previous period (3.35%). A positive association was found between its positivity and the period of 2009-2012. PMID:24937839

  19. Telomerase antagonist imetelstat increases radiation sensitivity in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wu, Xuping; Zhang, Jing; Yang, Sijun; Kuang, Zhihui; Tan, Guolei; Yang, Gang; Wei, Qichun; Guo, Zhigang

    2017-01-13

    The morbidity and mortality of esophageal cancer is one of the highest around the world and the principal therapeutic method is radiation. Thus, searching for sensitizers with lower toxicity and higher efficiency to improve the efficacy of radiation therapy is critical essential. Our research group has previously reported that imetelstat, the thio-phosphoramidate oligonucleotide inhibitor of telomerase, can decrease cell proliferation and colony formation ability as well as increase DNA breaks induced by radiation in esophageal cancer cells. Further study in this project showed that imetelstat significantly sensitized esophageal cancer cells to radiation in vitro. Later study showed that imetelstat leads to increased cell apoptosis. We also measured the expression level of several DNA repair and apoptosis signaling proteins. pS345 CHK1, γ-H2AX, p53 and caspase3 expression were up-regulated in imetelstat treated cells, identifying these factors as molecular markers. Mouse in vivo model using imetelstat at clinically achievable concentrations and fractionated irradiation scheme yielded results demonstrating radiosensitization effect. Finally, TUNEL assay, caspase 3 and Ki67 staining in tumor tissue proved that imetelstat sensitized esophageal cancer to radiation in vivo through promoting cell apoptosis and inhibiting cell proliferation. Our study supported imetelstat increase radiation sensitivity of esophageal squamous cell carcinoma through inducing cell apoptosis and the specific inhibitor of telomerase might serve as a potential novel therapeutic tool for esophageal squamous cell carcinoma therapy.

  20. Increasing measurement sensitivity for the electron's electric dipole moment using trapped molecular ions

    Science.gov (United States)

    Zhou, Yan; Gresh, Daniel; Cairncross, William; Grau, Matt; Ng, Kia Boon; Ni, Yiqi; Cornell, Eric; Ye, Jun

    2016-05-01

    Based on our latest measurements of the electron's electric dipole moment (eEDM) using trapped HfF+ ions, after 100 hours of data collection, the statistical error still dominates in our overall uncertainty budget. Overcoming the bottleneck of limited statistical sensitivity can increase the precision of the eEDM measurement directly. Here, we present the progress of three ongoing experiments: (1) applying STImulated Raman Adiabatic Passage (STIRAP) with rotating linear polarization for increased coherent population transfer from the ground X1Σ+ state to the eEDM-sensitive 3Δ1 state; (2) implementing a new ion-counting detector toward shot-noise limited sensitivity with significant suppression technical noise; (3) exploring the possibility of using the ground 3Δ1 state of ThF+ ions to realize a larger effective electric field and a longer coherence time. These experiments provide a route towards an order of magnitude increase in statistical sensitivity in the second generation of measurements.

  1. Stochasticity in Ca2+ increase in spines enables robust and sensitive information coding.

    Directory of Open Access Journals (Sweden)

    Takuya Koumura

    Full Text Available A dendritic spine is a very small structure (∼0.1 µm3 of a neuron that processes input timing information. Why are spines so small? Here, we provide functional reasons; the size of spines is optimal for information coding. Spines code input timing information by the probability of Ca2+ increases, which makes robust and sensitive information coding possible. We created a stochastic simulation model of input timing-dependent Ca2+ increases in a cerebellar Purkinje cell's spine. Spines used probability coding of Ca2+ increases rather than amplitude coding for input timing detection via stochastic facilitation by utilizing the small number of molecules in a spine volume, where information per volume appeared optimal. Probability coding of Ca2+ increases in a spine volume was more robust against input fluctuation and more sensitive to input numbers than amplitude coding of Ca2+ increases in a cell volume. Thus, stochasticity is a strategy by which neurons robustly and sensitively code information.

  2. Complex interactions between climate change and toxicants: evidence that temperature variability increases sensitivity to cadmium.

    Science.gov (United States)

    Kimberly, David A; Salice, Christopher J

    2014-07-01

    The Intergovernmental Panel on Climate Change projects that global climate change will have significant impacts on environmental conditions including potential effects on sensitivity of organisms to environmental contaminants. The objective of this study was to test the climate-induced toxicant sensitivity (CITS) hypothesis in which acclimation to altered climate parameters increases toxicant sensitivity. Adult Physa pomilia snails were acclimated to a near optimal 22 °C or a high-normal 28 °C for 28 days. After 28 days, snails from each temperature group were challenged with either low (150 μg/L) or high (300 μg/L) cadmium at each temperature (28 or 22 °C). In contrast to the CITS hypothesis, we found that acclimation temperature did not have a strong influence on cadmium sensitivity except at the high cadmium test concentration where snails acclimated to 28 °C were more cadmium tolerant. However, snails that experienced a switch in temperature for the cadmium challenge, regardless of the switch direction, were the most sensitive to cadmium. Within the snails that were switched between temperatures, snails acclimated at 28 °C and then exposed to high cadmium at 22 °C exhibited significantly greater mortality than those snails acclimated to 22 °C and then exposed to cadmium at 28 °C. Our results point to the importance of temperature variability in increasing toxicant sensitivity but also suggest a potentially complex cost of temperature acclimation. Broadly, the type of temporal stressor exposures we simulated may reduce overall plasticity in responses to stress ultimately rendering populations more vulnerable to adverse effects.

  3. Increased photic sensitivity for phase resetting but not melatonin suppression in Siberian hamsters under short photoperiods.

    Science.gov (United States)

    Glickman, G L; Harrison, E M; Elliott, J A; Gorman, M R

    2014-03-01

    Light regulates a variety of behavioral and physiological processes, including activity rhythms and hormone secretory patterns. Seasonal changes in the proportion of light in a day (photoperiod) further modulate those functions. Recently, short (SP) versus long days (LP) were found to markedly increase light sensitivity for phase shifting in Syrian hamsters. To our knowledge, photoperiod effects on light sensitivity have not been studied in other rodents, nor is it known if they generalize to other circadian responses. We tested whether photic phase shifting and melatonin suppression vary in Siberian hamsters maintained under LP or SP. Select irradiances of light were administered, and shifts in activity were determined. Photic sensitivity for melatonin suppression was examined in a separate group of animals via pulses of light across a 4 log-unit photon density range, with post-pulse plasma melatonin levels determined via RIA. Phase shifting and melatonin suppression were greater at higher irradiances for both LP and SP. The lower irradiance condition was below threshold for phase shifts in LP but not SP. Melatonin suppression did not vary by photoperiod, and the half saturation constant for fitted sigmoid curves was similar under LP and SP. Thus, the photoperiodic modulation of light sensitivity for phase shifting is conserved across two hamster genera. The dissociation of photoperiod effects on photic phase shifting and melatonin suppression suggests that the modulation of sensitivity occurs downstream of the common retinal input pathway. Understanding the mechanistic basis for this plasticity may yield therapeutic targets for optimizing light therapy practices.

  4. PCM1 Depletion Inhibits Glioblastoma Cell Ciliogenesis and Increases Cell Death and Sensitivity to Temozolomide

    Directory of Open Access Journals (Sweden)

    Lan B. Hoang-Minh

    2016-10-01

    Full Text Available A better understanding of the molecules implicated in the growth and survival of glioblastoma (GBM cells and their response to temozolomide (TMZ, the standard-of-care chemotherapeutic agent, is necessary for the development of new therapies that would improve the outcome of current GBM treatments. In this study, we characterize the role of pericentriolar material 1 (PCM1, a component of centriolar satellites surrounding centrosomes, in GBM cell proliferation and sensitivity to genotoxic agents such as TMZ. We show that PCM1 is expressed around centrioles and ciliary basal bodies in patient GBM biopsies and derived cell lines and that its localization is dynamic throughout the cell cycle. To test whether PCM1 mediates GBM cell proliferation and/or response to TMZ, we used CRISPR/Cas9 genome editing to generate primary GBM cell lines depleted of PCM1. These PCM1-depleted cells displayed reduced AZI1 satellite protein localization and significantly decreased proliferation, which was attributable to increased apoptotic cell death. Furthermore, PCM1-depleted lines were more sensitive to TMZ toxicity than control lines. The increase in TMZ sensitivity may be partly due to the reduced ability of PCM1-depleted cells to form primary cilia, as depletion of KIF3A also ablated GBM cells' ciliogenesis and increased their sensitivity to TMZ while preserving PCM1 localization. In addition, the co-depletion of KIF3A and PCM1 did not have any additive effect on TMZ sensitivity. Together, our data suggest that PCM1 plays multiple roles in GBM pathogenesis and that associated pathways could be targeted to augment current or future anti-GBM therapies.

  5. ACTH-like peptides increase pain sensitivity and antagonize opiate analgesia

    Science.gov (United States)

    Heybach, J. P.; Vernikos, J.

    1981-01-01

    The role of the pituitary and of ACTH in pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 C. Hypophysectomy reduced pain sensitivity, and this effect was reversed by the intracerebroventricular (ICV) injection of the opiate antagonist naloxone. Similarly, the analgesia produced by a dose of morphine was antagonized by the administration of ACTH or alpha-MSH. The peripheral injection of ACTH or alpha-MSH in normal rats did not increase pain sensitivity. However, ACTH administered ICV increased pain sensivity within 10 min. The results indicate that the pituitary is the source of an endogenous opiate antagonist and hyperalgesic factor and that this factor is ACTH or an ACTH-like peptide. This activity resides in the N-terminal portion of the ACTH molecule since ACTH sub 4-10 is not active in this respect, nor does this activity require a free N-terminal serine since alpha-MSH appears to be almost as potent as the ACTH sub 1-24 peptide. It is concluded that ACTH-like peptides of pituitary origin act as endogenous hyperalgesic and opiate antagonistic factors.

  6. Increased sensitivity to ET-1 in rat cerebral arteries following organ culture

    DEFF Research Database (Denmark)

    Hansen-Schwartz, J; Edvinsson, L

    2000-01-01

    Endothelin-1 (ET-1) is recognized as being involved in the pathophysiology of cerebrovascular diseases. Using organ culture as a model for possible pathological changes we studied changes in ET(A) and ETB receptor function using a sensitive in vitro method. We observed an up-regulation of the ET......(B) receptor and an amazingly increased sensitivity to ET-1 by 3 log units in pEC50; pEC50(fresh) was 8.7 +/- 0.1, and pEC50(cultured) was 11.7 +/- 0.3. pA2 for FR139317 in the fresh vessel was 7.0 +/- 0.2 whereas it could not be obtained for the cultured vessel, indicating a possible cross-talk between the ET......(A) and ET(B) receptors. The increased sensitivity to ET-1 could also take place during cerebrovascular disease such as stroke or haemorrhage rendering the vessels considerably more sensitive to ET-1....

  7. Competition increases sensitivity of wheat (Triticum aestivum to biotic plant-soil feedback.

    Directory of Open Access Journals (Sweden)

    W H Gera Hol

    Full Text Available Plant-soil feedback (PSF and plant competition play an important role in structuring vegetation composition, but their interaction remains unclear. Recent studies suggest that competing plants could dilute pathogenic effects, whereas the standing view is that competition may increase the sensitivity of the focal plant to PSF. In agro-ecosystems each of these two options would yield contrasting outcomes: reduced versus enhanced effects of weeds on crop biomass production. To test the effect of competition on sensitivity to PSF, we grew Triticum aestivum (Common wheat with and without competition from a weed community composed of Vicia villosa, Chenopodium album and Myosotis arvensis. Plants were grown in sterilized soil, with or without living field inoculum from 4 farms in the UK. In the conditioning phase, field inocula had both positive and negative effects on T. aestivum shoot biomass, depending on farm. In the feedback phase the differences between shoot biomass in T. aestivum monoculture on non-inoculated and inoculated soils had mostly disappeared. However, T. aestivum plants growing in mixtures in the feedback phase were larger on non-inoculated soil than on inoculated soil. Hence, T. aestivum was more sensitive to competition when the field soil biota was present. This was supported by the statistically significant negative correlation between shoot biomass of weeds and T. aestivum, which was absent on sterilized soil. In conclusion, competition in cereal crop-weed systems appears to increase cereal crop sensitivity to soil biota.

  8. Dual-arm multiple-reflection Michelson interferometer for large multiple reflections and increased sensitivity

    Science.gov (United States)

    Joenathan, Charles; Bernal, Ashley; Woonghee, Youn; Bunch, Robert M.; Hakoda, Christopher

    2016-02-01

    Michelson interferometer is one of the most popular optical interferometric systems used in optical metrology. Typically, Michelson interferometers are used to measure object displacement with wavefront shapes to one half of the laser wavelength. As testing components and device sizes reduce to micro and nano size, a sensitivity of half the wavelength of light cannot be used to measure several hundred picometer displacement. Multiple-reflection interferometers have been proposed and are used to increase the sensitivity in a Michelson interferometer; however, when altering the number of reflections, the system alignment becomes cumbersome. We describe some of the problems associated with the current multiple-reflection interferometer and introduce a setup for matching path lengths to increase the resolution and allow for the reduction of the stringent requirement on the coherence length of the lasers used. Theoretically, we show that more than 1000 reflections can be achieved. Experimental results of up to 100 reflections are presented in this paper.

  9. Voltage-Sensitive Load Controllers for Voltage Regulation and Increased Load Factor in Distribution Systems

    DEFF Research Database (Denmark)

    Douglass, Philip James; Garcia-Valle, Rodrigo; Østergaard, Jacob

    2014-01-01

    consumption which can be mapped to temperature setpoint offsets of thermostat controlled loads. In networks where a lower voltage level corresponds to high system load (and vice versa), this controller acts to regulate voltage and increase the load factor. Simulations are conducted on low- and medium-voltage......This paper presents a novel controller design for controlling appliances based on local measurements of voltage. The controller finds the normalized voltage deviation accounting for the sensitivity of voltage measurements to appliance state. The controller produces a signal indicating desired power...... distribution systems with residential loads including voltage-sensitive water heaters. In low-voltage systems, the results of the simulations show the controller to be effective at reducing the extremes of voltage and increasing the load factor while respecting end-use temperature constraints. In medium-voltage...

  10. A continuous-flow ATP amplification system for increasing the sensitivity of quantitative bioluminescence assay

    OpenAIRE

    Satoh, Tetsuya; Shinoda, Yasuharu; Alexandrov, Maxym; Kuroda, Akio; Murakami, Yuji

    2008-01-01

    We constructed a novel ATP amplification reactor using a continuous-flow system, and this allowed us to increase the sensitivity of quantitative bioluminescence assay by controlling the number of ATP amplification cycles. We previously developed a bioluminescence assay coupled with ATP amplification using a batch system. However, it was difficult to control the number of amplification cycles. In this study, ATP amplification was performed using a continuous-flow system, and significant linear...

  11. The Proton-Activated Receptor GPR4 Modulates Glucose Homeostasis by Increasing Insulin Sensitivity

    Directory of Open Access Journals (Sweden)

    Luca Giudici

    2013-11-01

    Full Text Available Background: The proton-activated G protein-coupled receptor GPR4 is expressed in many tissues including white adipose tissue. GPR4 is activated by extracellular protons in the physiological pH range (i.e. pH 7.7 - 6.8 and is coupled to the production of cAMP. Methods: We examined mice lacking GPR4 and examined glucose tolerance and insulin sensitivity in young and aged mice as well as in mice fed with a high fat diet. Expression profiles of pro- and anti-inflammatory cytokines in white adipose tissue, liver and skeletal muscle was assessed. Results: Here we show that mice lacking GPR4 have an improved intraperitoneal glucose tolerance test and increased insulin sensitivity. Insulin levels were comparable but leptin levels were increased in GPR4 KO mice. Gpr4-/- showed altered expression of PPARα, IL-6, IL-10, TNFα, and TGF-1β in skeletal muscle, white adipose tissue, and liver. High fat diet abolished the differences in glucose tolerance and insulin sensitivity between Gpr4+/+ and Gpr4-/- mice. In contrast, in aged mice (12 months old, the positive effect of GPR4 deficiency on glucose tolerance and insulin sensitivity was maintained. Liver and adipose tissue showed no major differences in the mRNA expression of pro- and anti-inflammatory factors between aged mice of both genotypes. Conclusion: Thus, GPR4 deficiency improves glucose tolerance and insulin sensitivity. The effect may involve an altered balance between pro- and anti-inflammatory factors in insulin target tissues.

  12. Low-dose Simvastatin Increases Skeletal Muscle Sensitivity to Caffeine and Halothane

    Institute of Scientific and Technical Information of China (English)

    Xu-lei Cui; Ying-lin Wang; Gang Tan; Ai-lun Luo; Xiang-yang Guo

    2016-01-01

    Objective To determine whether the myotoxic side effects of statin simvastatin affect skeletal muscle’s sensitivity to caffeine and halothane. Methods Primary cultured neonate rat skeletal myotubes were treated with 0.01-5.0μmol/L simvastatin for 48 hours. MTT was used to evaluate cellular viability. The gross morphology and microstructure of the myotubes were observed with a light and electron microscope, respectively. The intracellular calcium concentrations ([Ca2+]i) at rest and in response to caffeine and halothane were investigated by fluorescence calcium imaging. Data were analyzed byanalysis of variance (ANOVA) test. Results Simvastatin (0.01-5.0μmol/L) decreased myotube viability, changed their morphological features and microstructure, and increased the resting [Ca2+]i in a dose-dependent manner. Simvastatin did not change myotube’s sensitivity to low doses of caffeine (0.625-2.5 mmol/L) or halothane (1.0-5.0 mmol/L). In response to high-dose caffeine (10.0 mmol/L, 20.0 mmol/L) and halothane (20.0 mmol/L, 40.0 mmol/L), myotubes treated with 0.01μmol/L simvastatin showed a significant increase in sensitivity, but those treated with 1.0μmol/L and 5.0μmol/L simvastatin showed a significant decrease. The sarcoplasmic reticulum Ca2+ storage peaked in the myotubes treated with 0.01μmol/L simvastatin, but it decreased when cells were treated with higher doses of simvastatin (0.1-5.0μmol/L). Conclusions The myotoxic side effect of simvastatin was found to change the sensitivity of myotubes in response to high-dose caffeine and halothane. When dose was low, sensitivity increased mainly because of increased Ca2+ content in the sarcoplasmic reticulum, which might explain why some individuals with statin-induced myotoxic symptoms may show positivecaffeine-halothane contracture test results. However, when the dose was high and the damage to the myotubes was severer, sensitivity was lower. It is here supposed that the damage itself might put individuals with

  13. Envelope enhancement increases cortical sensitivity to interaural envelope delays with acoustic and electric hearing.

    Directory of Open Access Journals (Sweden)

    Douglas E H Hartley

    Full Text Available Evidence from human psychophysical and animal electrophysiological studies suggests that sensitivity to interaural time delay (ITD in the modulating envelope of a high-frequency carrier can be enhanced using half-wave rectified stimuli. Recent evidence has shown potential benefits of equivalent electrical stimuli to deaf individuals with bilateral cochlear implants (CIs. In the current study we assessed the effects of envelope shape on ITD sensitivity in the primary auditory cortex of normal-hearing ferrets, and profoundly-deaf animals with bilateral CIs. In normal-hearing animals, cortical sensitivity to ITDs (±1 ms in 0.1-ms steps was assessed in response to dichotically-presented i sinusoidal amplitude-modulated (SAM and ii half-wave rectified (HWR tones (100-ms duration; 70 dB SPL presented at the best-frequency of the unit over a range of modulation frequencies. In separate experiments, adult ferrets were deafened with neomycin administration and bilaterally-implanted with intra-cochlear electrode arrays. Electrically-evoked auditory brainstem responses (EABRs were recorded in response to bipolar electrical stimulation of the apical pair of electrodes with singe biphasic current pulses (40 µs per phase over a range of current levels to measure hearing thresholds. Subsequently, we recorded cortical sensitivity to ITDs (±800 µs in 80-µs steps within the envelope of SAM and HWR biphasic-pulse trains (40 µs per phase; 6000 pulses per second, 100-ms duration over a range of modulation frequencies. In normal-hearing animals, nearly a third of cortical neurons were sensitive to envelope-ITDs in response to SAM tones. In deaf animals with bilateral CI, the proportion of ITD-sensitive cortical neurons was approximately a fifth in response to SAM pulse trains. In normal-hearing and deaf animals with bilateral CI the proportion of ITD sensitive units and neural sensitivity to ITDs increased in response to HWR, compared with SAM stimuli

  14. Heat Shock Protein translocation induced by membrane fluidization increases tumor-cell sensitivity to chemotherapeutic drugs.

    Science.gov (United States)

    Dempsey, Nina C; Ireland, H Elyse; Smith, Carly M; Hoyle, Christine F; Williams, John H H

    2010-10-28

    Treatment of chronic lymphocytic leukemia (CLL) remains a challenge due to the frequency of drug resistance amongst patients. Improving the delivery of chemotherapeutic agents while reducing the expression of anti-apoptotic Heat Shock Proteins (HSPs) within the cancer cells may facilitate in overcoming this drug resistance. We demonstrate for the first time that sub-lethal doses of chemotherapeutic agents can be combined with membrane fluidizing treatments to produce a significant increase in drug efficacy and apoptosis in vitro. We show that fluidizers result in a transient decrease in intracellular HSPs, resulting in increased tumor-cell sensitivity and a membrane-associated induction of HSP gene expression.

  15. Obesity Increases Sensitivity to Endotoxin Liver Injury: Implications for the Pathogenesis of Steatohepatitis

    Science.gov (United States)

    Yang, Shi Qi; Zhi Lin, Hui; Lane, M. Daniel; Clemens, Mark; Diehl, Anna Mae

    1997-03-01

    Genetically obese fatty/fatty rats and obese/obese mice exhibit increased sensitivity to endotoxin hepatotoxicity, quickly developing steatohepatitis after exposure to low doses of lipopolysaccharide (LPS). Among obese animals, females are more sensitive to endotoxin liver injury than males. LPS induction of tumor necrosis factor α (TNFα ), the proven affecter of endotoxin liver injury, is no greater in the livers, white adipose tissues, or sera of obese animals than in those of lean controls. Indeed, the lowest serum concentrations of TNF occur in female obese rodents, which exhibit the most endotoxin-induced liver injury. Several cytokines that modulate the biological activity of TNF are regulated abnormally in the livers of obese animals. After exposure to LPS, mRNA of interferon γ , which sensitizes hepatocytes to TNF toxicity, is overexpressed, and mRNA levels of interleukin 10, a TNF inhibitor, are decreased. The phagocytic activity of liver macrophages and the hepatic expression of a gene encoding a macrophage-specific receptor are also decreased in obesity. This new animal model of obesity-associated liver disease demonstrates that hepatic macrophage dysfunction occurs in obesity and suggests that this might promote steatohepatitis by sensitizing hepatocytes to endotoxin.

  16. Increased sensitivity to salt stress in tocopherol-deficient Arabidopsis mutants growing in a hydroponic system.

    Science.gov (United States)

    Ellouzi, Hasna; Hamed, Karim Ben; Cela, Jana; Müller, Maren; Abdelly, Chedly; Munné-Bosch, Sergi

    2013-02-01

    Recent studies suggest that tocopherols could play physiological roles in salt tolerance but the mechanisms are still unknown. In this study, we analyzed changes in growth, mineral and oxidative status in vte1 and vte4 Arabidopsis thaliana mutants exposed to salt stress. vte1 and vte4 mutants lack α-tocopherol, but only the vte1 mutant is additionally deficient in γ-tocopherol. Results showed that a deficiency in vitamin E leads to reduced growth and increased oxidative stress in hydroponically-grown plants. This effect was observed at early stages, not only in rosettes but also in roots. The vte1 mutant was more sensitive to salt-induced oxidative stress than the wild type and the vte4 mutant. Salt sensitivity was associated with (i) high contents of Na(+), (ii) reduced efficiency of PSII photochemistry (Fv/Fm ratio) and (iii) more pronounced oxidative stress as indicated by increased hydrogen peroxide and malondialdeyde levels. The vte 4 mutant, which accumulates γ- instead of α-tocopherol showed an intermediate sensitivity to salt stress between the wild type and the vte1 mutant. Contents of abscisic acid, jasmonic acid and the ethylene precursor, 1-aminocyclopropane-1-carboxylic acid were higher in the vte1 mutant than the vte4 mutant and wild type. It is concluded that vitamin E-deficient plants show an increased sensitivity to salt stress both in rosettes and roots, therefore indicating the positive role of tocopherols in stress tolerance, not only by minimizing oxidative stress, but also controlling Na(+)/K(+) homeostasis and hormonal balance.

  17. Alcohol acutely increases vascular reactivity together with insulin sensitivity in type 2 diabetic men.

    Science.gov (United States)

    Schaller, G; Kretschmer, S; Gouya, G; Haider, D G; Mittermayer, F; Riedl, M; Wagner, O; Pacini, G; Wolzt, M; Ludvik, B

    2010-01-01

    Moderate alcohol consumption is associated with increased insulin sensitivity and reduced cardiovascular risk. We hypothesized that this relates to a direct effect of alcohol and therefore investigated whether acute alcohol intake altered insulin sensitivity or endothelial function in patients with type 2 diabetes. In an open-label two period design, the effect of a single oral dose of 40 g of alcohol (168 ml 40% vodka) on an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT) and on endothelium-dependent (flow mediated, FMD) or endothelium-independent (glyceroltrinitrate (GTN)-induced) vasodilation of the brachial artery measured by ultrasound was studied. Experiments were carried out in twelve male patients with type 2 diabetes mellitus (64+/-6 years, body mass index 28.4+/-5.7 kg/m (2)). Baseline insulin sensitivity index (S (I)) was 1.10+/-0.34 min (-1).microU (-1).ml, baseline FMD was +4.1+/-3.0%, and GTN-induced vasodilation +7.4+/-2.3% from resting brachial artery diameter. Acute alcohol intake increased alcohol plasma levels to 0.33+/-0.04 per thousand, S (I) to 1.86+/-0.45 min (-1).microU (-1).ml (p<0.05), and FMD to +8.2+/-2.8% (p<0.05), while GTN-induced dilation remained unchanged. No relationship was detectable between the observed changes. We conclude that alcohol intake acutely increases endothelium-dependent brachial artery vasodilation in patients with type 2 diabetes together with insulin sensitivity. This acute effect might explain some beneficial effects of low alcohol consumption in epidemiological observations.

  18. Is glycyrrhizin sensitivity increased in anorexia nervosa and should licorice be avoided? Case report and review of the literature

    DEFF Research Database (Denmark)

    Støving, René K; Lingqvist, Linnéa E; Bonde, Rasmus K

    2011-01-01

    low daily dose of licorice suggests high glycyrrhizin sensitivity. CONCLUSION: Patients with anorexia nervosa not only have decreased food intake but also selective and sometimes bizarre eating habits that, in association with increased sensitivity to glycyrrhizin, may cause severe hypokalemia....

  19. Spatial covert attention increases contrast sensitivity across the CSF: support for signal enhancement

    Science.gov (United States)

    Carrasco, M.; Penpeci-Talgar, C.; Eckstein, M.

    2000-01-01

    This study is the first to report the benefits of spatial covert attention on contrast sensitivity in a wide range of spatial frequencies when a target alone was presented in the absence of a local post-mask. We used a peripheral precue (a small circle indicating the target location) to explore the effects of covert spatial attention on contrast sensitivity as assessed by orientation discrimination (Experiments 1-4), detection (Experiments 2 and 3) and localization (Experiment 3) tasks. In all four experiments the target (a Gabor patch ranging in spatial frequency from 0.5 to 10 cpd) was presented alone in one of eight possible locations equidistant from fixation. Contrast sensitivity was consistently higher for peripherally- than for neutrally-cued trials, even though we eliminated variables (distracters, global masks, local masks, and location uncertainty) that are known to contribute to an external noise reduction explanation of attention. When observers were presented with vertical and horizontal Gabor patches an external noise reduction signal detection model accounted for the cueing benefit in a discrimination task (Experiment 1). However, such a model could not account for this benefit when location uncertainty was reduced, either by: (a) Increasing overall performance level (Experiment 2); (b) increasing stimulus contrast to enable fine discriminations of slightly tilted suprathreshold stimuli (Experiment 3); and (c) presenting a local post-mask (Experiment 4). Given that attentional benefits occurred under conditions that exclude all variables predicted by the external noise reduction model, these results support the signal enhancement model of attention.

  20. Increasing amperometric biosensor sensitivity by length fractionated single-walled carbon nanotubes

    DEFF Research Database (Denmark)

    Tasca, Federico; Gorton, Lo; Wagner, Jakob Birkedal

    2008-01-01

    In this work the sensitivity-increasing effect of single-walled carbon nanotubes (SWCNTs) in amperometric biosensors, depending on their average length distribution, was studied. For this purpose the SWCNTs were oxidatively shortened and subsequently length separated by size exclusion chromatogra......In this work the sensitivity-increasing effect of single-walled carbon nanotubes (SWCNTs) in amperometric biosensors, depending on their average length distribution, was studied. For this purpose the SWCNTs were oxidatively shortened and subsequently length separated by size exclusion...... chromatography. Transmission electron micrographs of different fractions of SWCNTs were collected. Diaphorase ``wired'' to an osmium redox polymer was blended with the shortened SWCNTs of different lengths. Depending on the average length of the SWCNTs the sensitivity of the amperometric biosensor model system...... limit was 1 mu M. The biosensor exhibited excellent electrocatalytic properties. Even at relatively high NADH concentrations the oxidative current was limited by the diffusion rate of NADH. (C) 2008 Elsevier B.V. All rights reserved....

  1. Reduced mtDNA copy number increases the sensitivity of tumor cells to chemotherapeutic drugs.

    Science.gov (United States)

    Mei, H; Sun, S; Bai, Y; Chen, Y; Chai, R; Li, H

    2015-04-02

    Many cancer drugs are toxic to cells by activating apoptotic pathways. Previous studies have shown that mitochondria have key roles in apoptosis in mammalian cells, but the role of mitochondrial DNA (mtDNA) copy number variation in the pathogenesis of tumor cell apoptosis remains largely unknown. We used the HEp-2, HNE2, and A549 tumor cell lines to explore the relationship between mtDNA copy number variation and cell apoptosis. We first induced apoptosis in three tumor cell lines and one normal adult human skin fibroblast cell line (HSF) with cisplatin (DDP) or doxorubicin (DOX) treatment and found that the mtDNA copy number significantly increased in apoptotic tumor cells, but not in HSF cells. We then downregulated the mtDNA copy number by transfection with shRNA-TFAM plasmids or treatment with ethidium bromide and found that the sensitivity of tumor cells to DDP or DOX was significantly increased. Furthermore, we observed that levels of reactive oxygen species (ROS) increased significantly in tumor cells with lower mtDNA copy numbers, and this might be related to a low level of antioxidant gene expression. Finally, we rescued the increase of ROS in tumor cells with lipoic acid or N-acetyl-L-cysteine and found that the apoptosis rate decreased. Our studies suggest that the increase of mtDNA copy number is a self-protective mechanism of tumor cells to prevent apoptosis and that reduced mtDNA copy number increases ROS levels in tumor cells, increases the tumor cells' sensitivity to chemotherapeutic drugs, and increases the rate of apoptosis. This research provides evidence that mtDNA copy number variation might be a promising new therapeutic target for the clinical treatment of tumors.

  2. Stevioside from Stevia rebaudiana Bertoni Increases Insulin Sensitivity in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Nabilatul Hani Mohd-Radzman

    2013-01-01

    Full Text Available Stevioside from Stevia rebaudiana has been reported to exert antihyperglycemic effects in both rat and human subjects. There have been few studies on these effects in vitro. In this paper, radioactive glucose uptake assay was implemented in order to assess improvements in insulin sensitivity in 3T3-L1 cells by elevation of glucose uptake following treatment with stevioside. Oil Red-O staining and MTT assay were utilized to confirm adipocyte differentiation and cell viability, respectively. Findings from this research showed a significant increase in absorbance values in mature adipocytes following Oil Red-O staining, confirming the differentiation process. Stevioside was noncytotoxic to 3T3-L1 cells as cell viability was reduced by a maximum of 17%, making it impossible to determine its IC50. Stevioside increased glucose uptake activities by 2.1 times (p<0.001 in normal conditions and up to 4.4 times (p<0.001 in insulin-resistant states. At times, this increase was higher than that seen in positive control group treated with rosiglitazone maleate, an antidiabetic agent. Expressions of pY20 and p-IRS1 which were measured via Western blot were improved by stevioside treatment. In conclusion, stevioside has direct effects on 3T3-L1 insulin sensitivity via increase in glucose uptake and enhanced expression of proteins involved in insulin-signalling pathway.

  3. Increased Sensitivity of Magnetoelectric Sensors at Low Frequencies Using Magnetic Field Modulation

    Science.gov (United States)

    Petrie, Jonathan; Viehland, Dwight; Gray, David; Mandal, Sanjay; Sreenivasulu, Gollapudi; Srinivasan, Gopalan; Edelstein, Alan

    2012-02-01

    Magnetoelectric (ME) laminate sensors are vector magnetometers that can detect pT magnetic fields at 1 kHz, although sensitivity may be reduced at lower frequencies. These passive sensors consist of alternating layers of magnetostrictive and piezoelectric materials. A magnetic field causes the magnetostrictive layer to strain the piezoelectric material and create measurable charge. We have shownootnotetextTo be published in Journal of Applied Physics. that since the strain response is a nonlinear function of the bias field, sweeping the magnetic bias on the magnetostrictive layer can modulate the ME response and increase the operating frequency of the sensor. This upward shift lowers the 1/f noise and increases the signal amplitude if the new operating frequency is near a mechanical resonance mode of the sensor. Using this modulation technique, the low frequency sensitivity has been improved by more than an order of magnitude and we have achieved a detectivity of 7 pT/Hz at1 Hz. In addition to increasing the magnetic signal frequency, we can use magnetic modulation to increase the operating frequency of acoustic signals detected by these sensors. This occurs because the ME sensors are nonlinear devices. In these cases using magnetic field modulation, the signal appears as sidebands around the modulation frequency.

  4. The relationship between cocaine-induced increases in NAC1 and behavioral sensitization.

    Science.gov (United States)

    Wang, P J; Stromberg, Michael; Replenski, Stephen; Snyder-Mackler, Alexander; Mackler, Scott A

    2003-04-01

    Repeated exposure to cocaine can cause long-term behavioral changes in mammals, including an augmented locomotor response known as behavioral sensitization. A major goal of research is the identification of molecules associated with these behaviors. NAC1, a member of the POZ/BTB transcription factor family, exhibited increased mRNA levels in the nucleus accumbens of the rat weeks after cocaine use. NAC1 exists as two isoforms, each demonstrating the ability to inhibit transcription, but to different extents. The present experiments examined the time course for both NAC1 isoforms after five consecutive days of systemic cocaine administration in male rats. Tissues were collected from several central nervous system regions and underwent Western blot analysis. There was significantly greater expression of the long isoform, lNAC1 (cocaine 1.341+/-0.641; saline 1+/-0.321; P=.044), and the short isoform, sNAC1 (cocaine 3.038+/-2.816; saline 1+/-0.720; P=.001), in the nucleus accumbens of cocaine-treated rats. The olfactory tubercle also showed a significant increase, but only in sNAC1 expression and at only one time period. No other significant differences were observed for either isoform of NAC1 in any other brain region. The expression of lNAC1 exhibited an inverse relationship with behavioral sensitization in rats 1-3 months following repeated cocaine injections predicting approximately 40% of the variance in the behavior variables (R(2)=.387; and P=.031 for distance and P=.025 for ambulatory count). These results indicate that NAC1 expression is increased for a period of several months after chronic cocaine exposure. Furthermore, these data suggest that NAC1 may function as an endogenous inhibitor of behavioral sensitization. NAC1 represents a target for future studies examining cocaine-induced behavioral changes.

  5. Repetitive hyperbaric oxygen treatment increases insulin sensitivity in diabetes patients with acute intracerebral hemorrhage

    Science.gov (United States)

    Xu, Qian; Wei, Yi-ting; Fan, Shuang-bo; Wang, Liang; Zhou, Xiao-ping

    2017-01-01

    Aim The role of hyperbaric oxygen therapy (HBOT) in the treatment of acute ischemic stroke is controversial. This study aims to investigate whether the peripheral insulin sensitivity of type 2 diabetes patients suffering from intracerebral hemorrhage can be increased after HBOT. Methods Fifty-two type 2 diabetes participants were recruited after being diagnosed with intracerebral hemorrhage in our hospital. Insulin sensitivity was measured by the glucose infusion rate during a hyperinsulinemic euglycemic clamp (80 mU m−2 min−1) at baseline and 10 and 30 days after HBOT sessions. Serum insulin, fasting glucose, and hemoglobin A1C were measured in fasting serum at baseline and after HBOT sessions. In addition, early (∼10 days after onset) and late (1 month after onset) outcomes (National Institutes of Health Stroke Scale, NIHSS scores) and efficacy (changes of NIHSS scores) of HBOT were evaluated. Results In response to HBOT, the glucose infusion rate was increased by 37.8%±5.76% at 1 month after onset compared with baseline. Reduced serum insulin, fasting glucose, and hemoglobin A1C were observed after HBOT. Both early and late outcomes of the HBOT group were improved compared with baseline (P<0.001). In the control group, there was significant difference only in the late outcome (P<0.05). In the assessment of efficacy, there were statistically significant differences between the groups when comparing changes in NIHSS scores at 10 days and 1 month after onset (P<0.05). Conclusion Peripheral insulin sensitivity was increased following HBOT in type 2 diabetes patients with intracerebral hemorrhage. The HBOT used in this study may be effective for diabetes patients with acute stroke and is a safe and harmless adjunctive treatment. PMID:28228657

  6. Altered ATP-sensitive potassium channels may underscore obesity-triggered increase in blood pressure

    Institute of Scientific and Technical Information of China (English)

    Li-hong FAN; Hong-yan TIAN; Ai-qun MA; Zhi HU; Jian-hua HUO; Yong-xiao CAO

    2008-01-01

    Aim:To determine whether ATP-sensitive potassium channels are altered in VSMC from arotas and mesenteric arteries of obese rat,and their association with obesity-triggered increase in blood pressure.Methods:Obesity was induced by 24 weeks of high-fat diet feeding in male Sprague-Dawley rats.Control rats were fed with standard laboratory rat chow.Blood pressure and body weight of these rats were measured every 4 weeks.At the end of 24 weeks,KATP channel-mediated relaxation responses in the aortas and mesenteric arteries,KATP channel current,and gene expression were examined,respectively.Results:Blood pres-sure and body weight were increased in rats fed with high-fat diet.KATP channel-mediated relaxation responses,currents,and KATP expression in VSMC of both aortas and mesenteric arteries were inhibited in these rats.Conclusion:Altered ATP-sensitive potassium channels in obese rats may underscore obesity-triggered increase in blood pressure.

  7. Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels.

    Science.gov (United States)

    Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B; Dong, Xiao; Wang, Hongjun

    2015-05-28

    Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice.

  8. Reduced thermal sensitivity and increased opioidergic tone in the TASTPM mouse model of Alzheimer's disease.

    Science.gov (United States)

    Aman, Yahyah; Pitcher, Thomas; Simeoli, Raffaele; Ballard, Clive; Malcangio, Marzia

    2016-10-01

    Individuals with Alzheimer's disease (AD) are in susceptible patient groups in which pain is an important clinical issue that is often underdiagnosed. However, it is unclear whether decreased pain complaints in patients with AD result from elevated pain tolerance or an impaired ability to communicate sensations. Here, we explored if AD-related pathology is present in key regions of the pain pathway and assessed whether nociceptive thresholds to acute noxious stimulation are altered in the double-mutant APPswe × PS1.M146V (TASTPM) transgenic mouse model of AD. TASTPM mice exhibited an age-dependant cognitive deficit at the age of 6 months, but not at 4 months, a deficit that was accompanied by amyloid plaques in the cortex, hippocampus, and thalamus. In the spinal cord, β-amyloid (APP/Aβ) immunoreactivity was observed in dorsal and ventral horn neurons, and the expression of vesicular glutamate transporter 2 (VGLUT2) was significantly reduced, while the expression of the inhibitory peptides enkephalins was increased in TASTPM dorsal horn, consistent with an increased inhibitory tone. TASTPM mice displayed reduced sensitivity to acute noxious heat, which was reversed by naloxone, an opioid antagonist. This study suggests that increased inhibition and decreased excitation in the spinal cord may be responsible for the reduced thermal sensitivity associated with AD-related pathology.

  9. Increased intracellular free calcium and sensitivity to angiotensin II in platelets of preeclamptic women.

    Science.gov (United States)

    Haller, H; Oeney, T; Hauck, U; Distler, A; Philipp, T

    1989-04-01

    Preeclampsia is characterized by a generalized vasoconstriction and increased vascular sensitivity to angiotensin II. Intracellular free calcium, implicated in vascular smooth muscle contraction, has been found to be elevated in platelets of other hypertensive disorders. We therefore measured intracellular free calcium concentrations by using the fluorescent probe quin-2 in platelets of six patients with preeclampsia and compared them to measurements in ten normotensive pregnant women and ten age-matched nonpregnant women. Intracellular free calcium was also determined in the preeclamptic women after delivery. We found that intracellular free calcium was slightly elevated in normal pregnancy (102 +/- 13 nmol/L v 87 +/- 17 nmol/L) but was markedly increased in preeclampsia (138 +/- 13 nmol/L, P less than .05). This increase disappeared six weeks after delivery (84 + 10 nmol/L, P less than .01). To investigate whether the increased intracellular free calcium was related to angiotensin II, the platelets were exposed to thrombin and angiotensin II in vitro. Exposure to thrombin and angiotensin II caused a dose-dependent increase in intracellular free calcium. The intracellular response to thrombin was not significantly different in the three groups. However, stimulation with angiotensin II revealed an increased response in intracellular free calcium in preeclampsia (P less than .05) that disappeared after delivery. Our findings show a sustained increase in platelet intracellular free calcium in preeclampsia and suggest a functional alteration of the angiotensin II receptor in this disease.

  10. Phagosomal degradation increases TLR access to bacterial ligands and enhances macrophage sensitivity to bacteria

    Science.gov (United States)

    Wolf, Andrea J.; Arruda, Andrea; Reyes, Christopher N.; Kaplan, Amber T.; Shimada, Takahiro; Shimada, Kenichi; Arditi, Moshe; Liu, George; Underhill, David M.

    2011-01-01

    Signaling by innate immune receptors initiates and orchestrates the overall immune responses to infection. Macrophage receptors recognizing pathogens can be broadly grouped into surface receptors and receptors restricted to intracellular compartments, such as phagosomes and the cytoplasm. There is an expectation that ingestion and degradation of microorganisms by phagocytes contributes to activation of intracellular innate receptors, although direct demonstrations of this are rare and many model ligands are studied in soluble form, outside of their microbial context. By comparing a wild-type strain of Staphylococcus aureus and a lysozyme-sensitive mutant, we have been able to directly address the role of degradation of live bacteria by mouse macrophages in determining the overall innate cellular inflammatory response. Our investigations revealed a biphasic response to S. aureus that consisted of an initial signal resulting from the engagement of surface TLR2, followed by a later, second wave on inflammatory gene induction. This second wave of inflammatory signaling was dependent on and correlated with the timing of bacterial degradation in phagosomes. We found that TLR2 signaling followed by TLR2/TLR9 signaling enhanced sensitivity to small numbers of bacteria. We further found that treating wild-type bacteria with the peptidoglycan synthesis-inhibiting antibiotic vancomycin made S. aureus more susceptible to degradation and resulted in increased inflammatory responses, similar to those observed for mutant degradation-sensitive bacteria. PMID:22031762

  11. Improved Sensing Pulses for Increased Human Head Depth Measurement Sensitivity With Electrical Impedance Spectroscopy

    Science.gov (United States)

    Lev, Michael H.

    2017-01-01

    This paper describes an improved electrical impedance spectroscopy (EIS) stimulus paradigm, based on dual-energy pulses using the stochastic Gabor function (SGF) that may more sensitively assess deep brain tissue impedance than current single-pulse paradigms. The SGF is a uniformly distributed noise, modulated by a Gaussian envelope, with a wide-frequency spectrum representation regardless of the stimuli energy, and is least compact in the sample frequency phase plane. Numerical results obtained using a realistic human head model confirm that two sequential SGF pulses at different energies can improve EIS depth sensitivity when used in a dual-energy subtraction scheme. Specifically, although the two SGF pulses exhibit different tissue current distributions, they maintain the broadband sensing pulse characteristics needed to generate all the frequencies of interest. Moreover, finite-difference time domain simulations show that this dual-energy excitation scheme is capable of reducing the amplitude of weighted current densities surface directly underneath the electrodes by approximately 3 million times versus single stimulation pulses, while maintaining an acceptable tissue conductivity distribution at depth. This increased sensitivity for the detection of small, deep impedance changes might be of value in potential future EIS applications, such as the portable, point-of-care detection of deep brain hemorrhage or infarction. PMID:24043365

  12. Increased retest reactivity by both patch and use test with methyldibromoglutaronitrile in sensitized individuals

    DEFF Research Database (Denmark)

    Jensen, Charlotte D; Johansen, Jeanne Duus; Menné, Torkil

    2006-01-01

    -exposure by both a patch test challenge and a use test with a liquid soap preserved with MDBGN. MDBGN dermatitis was elicited on the back and arms of sensitized individuals. One month later the previously eczematous areas were challenged with MDBGN. On the back, the test sites were patch-tested with a serial...... dilution of MDBGN and a use test was performed on the arms with an MDBGN-containing soap. A statistically significant increased response was seen on the areas with previous dermatitis on the back. Eight of the nine patients who developed dermatitis on the arms from the MDBGN-containing soap had...

  13. MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1

    Directory of Open Access Journals (Sweden)

    Peng Li

    2017-02-01

    Full Text Available Background/Aims: MicroRNA-218 (miR-218 is down-regulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. However, the involvement of miR-218 in chemo-sensitivity to cisplatin and the precise mechanism of this action remained unknown in bladder cancer. Methods: qRT-PCR was used to detect miR-218 and its target Glut1 expression in bladder cancer cell lines T24 and EJ. CCK-8 method was utilized to measure the cell viability. IC 50 was calculated via a probit regression model. Glut1 was detected by western blotting for analysis of potential mechanism. Luciferase reporter assay was utilized to validate Glut1 as a direct target gene of miR-218. The intracellular level of GSH and ROS were determined using a commercial colorimetric assay kit and 2’, 7’-dichlorodihydro-fluorescein diacetate, respectively. Results: Over-expression of miR-218 significantly reduced the rate of glucose uptake and total level of GSH and enhanced the chemo-sensitivity of bladder cancer to cisplatin. Mechanistically, Glut1 was found to be a direct and functional target of miR-218. Up-regulation of Glut1 could restore chemo-resistance in T24 and EJ cells. On the contrary, knockdown of Glut1 could generate a similar effect as up-regulating the expression of miR-218. Conclusions: MiR-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Restoration of miR-218 and repression of glut1 may provide a potential strategy to restore chemo-sensitivity in bladder cancer.

  14. Increasing Drought Sensitivity and Decline of Atlas Cedar (Cedrus atlantica in the Moroccan Middle Atlas Forests

    Directory of Open Access Journals (Sweden)

    Jesús Julio Camarero

    2011-09-01

    Full Text Available An understanding of the interactions between climate change and forest structure on tree growth are needed for decision making in forest conservation and management. In this paper, we investigated the relative contribution of tree features and stand structure on Atlas cedar (Cedrus atlantica radial growth in forests that have experienced heavy grazing and logging in the past. Dendrochronological methods were applied to quantify patterns in basal-area increment and drought sensitivity of Atlas cedar in the Middle Atlas, northern Morocco. We estimated the tree-to-tree competition intensity and quantified the structure in Atlas cedar stands with contrasting tree density, age, and decline symptoms. The relative contribution of tree age and size and stand structure to Atlas cedar growth decline was estimated by variance partitioning using partial-redundancy analyses. Recurrent drought events and temperature increases have been identified from local climate records since the 1970s. We detected consistent growth declines and increased drought sensitivity in Atlas cedar across all sites since the early 1980s. Specifically, we determined that previous growth rates and tree age were the strongest tree features, while Quercus rotundifolia basal area was the strongest stand structure measure related to Atlas cedar decline. As a result, we suggest that Atlas cedar forests that have experienced severe drought in combination with grazing and logging may be in the process of shifting dominance toward more drought-tolerant species such as Q. rotundifolia.

  15. Titanium dioxide nanoparticles increase sensitivity in the next generation of the water flea Daphnia magna.

    Directory of Open Access Journals (Sweden)

    Mirco Bundschuh

    Full Text Available The nanoparticle industry is expected to become a trillion dollar business in the near future. Therefore, the unintentional introduction of nanoparticles into the environment is increasingly likely. However, currently applied risk-assessment practices require further adaptation to accommodate the intrinsic nature of engineered nanoparticles. Combining a chronic flow-through exposure system with subsequent acute toxicity tests for the standard test organism Daphnia magna, we found that juvenile offspring of adults that were previously exposed to titanium dioxide nanoparticles exhibit a significantly increased sensitivity to titanium dioxide nanoparticles compared with the offspring of unexposed adults, as displayed by lower 96 h-EC(50 values. This observation is particularly remarkable because adults exhibited no differences among treatments in terms of typically assessed endpoints, such as sensitivity, number of offspring, or energy reserves. Hence, the present study suggests that ecotoxicological research requires further development to include the assessment of the environmental risks of nanoparticles for the next and hence not directly exposed generation, which is currently not included in standard test protocols.

  16. Sensitivity of mice to lipopolysaccharide is increased by a high saturated fat and cholesterol diet

    Directory of Open Access Journals (Sweden)

    Stevens Rachel L

    2007-11-01

    HCD increased the sensitivity of mice to LPS without affecting its plasma level. Although increased serum amyloid A and CD14 in the circulation may inhibit LPS actions, their overexpression, along with hepatic toll-like receptor-4 or other factors, may contribute to the heightened sensitivity to LPS.

  17. Hypoxia increases pulmonary arterial thromboxane receptor internalization independent of receptor sensitization.

    Science.gov (United States)

    Fediuk, J; Sikarwar, A S; Lizotte, P P; Hinton, M; Nolette, N; Dakshinamurti, S

    2015-02-01

    Persistent Pulmonary Hypertension of the Newborn (PPHN) is characterized by sustained vasospasm and an increased thromboxane:prostacyclin ratio. Thromboxane (TP) receptors signal via Gαq to mobilize IP3 and Ca(2+), causing pulmonary arterial constriction. We have previously reported increased TP internalization in hypoxic pulmonary arterial (PA) myocytes. Serum-deprived PA myocytes were grown in normoxia (NM) or hypoxia (HM) for 72 h. TP localization was visualized in agonist-naïve and -challenged NM and HM by immunocytochemistry. Pathways for agonist-induced TP receptor internalization were determined by inhibiting caveolin- or clathrin-mediated endocytosis, and caveolar fractionation. Roles of actin and tubulin in TP receptor internalization were assessed using inhibitors of tubulin, actin-stabilizing or -destabilizing agents. PKA, PKC or GRK activation and inhibition were used to determine the kinase responsible for post-agonist receptor internalization. Agonist-naïve HM had decreased cell surface TP, and greater TP internalization after agonist challenge. TP protein did not sort with caveolin-rich fractions. Inhibition of clathrin prevented TP internalization. Both actin-stabilizing and -destabilizing agents prevented TP endocytosis in NM, while normalizing TP internalization in HM. Velocity of TP internalization was unaffected by PKA activity, but PKC activation normalized TP receptor internalization in HM. GRK inhibition had no effect. We conclude that in hypoxic myocytes, TP is internalized faster and to a greater extent than in normoxic controls. Internalization of the agonist-challenged TP requires clathrin, dynamic actin and is sensitive to PKC activity. TP receptor trafficking and signaling in hypoxia are pivotal to understanding increased vasoconstrictor sensitivity.

  18. BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin

    Energy Technology Data Exchange (ETDEWEB)

    Oommen, Deepu [School of Biological Sciences, Plymouth University, Plymouth PL4 8AA (United Kingdom); Yiannakis, Dennis [Plymouth Oncology Centre, Derriford Hospital, Plymouth Hospitals NHS Trust, Plymouth PL6 8DH (United Kingdom); Jha, Awadhesh N., E-mail: a.jha@plymouth.ac.uk [School of Biological Sciences, Plymouth University, Plymouth PL4 8AA (United Kingdom)

    2016-02-15

    Highlights: • BRCA1 deficient cancer cells exhibit increased DNA damage upon auranofin treatment. • Auranofin induces apoptosis in BRCA1 deficient cancer cells despite the activation of Nrf2. • Antioxidant protects BRCA1 deficient cancer cells from auranofin. - Abstract: Auranofin, a thioredoxin reductase inhibitor and an anti-rheumatic drug is currently undergoing phase 2 clinical studies for repurposing to treat recurrent epithelial ovarian cancer. Previous studies have established that auranofin exerts its cytotoxic activity by increasing the production of reactive oxygen species (ROS). Breast cancer 1, early onset (BRCA1) is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from its key role in DNA repair, BRCA1 is also known to modulate cellular redox homeostasis by regulating the stability of anti-oxidant transcription factor, nuclear factor erythroid 2—related factor 2 (Nrf2) via direct protein–protein interaction. However, it is currently unknown whether BRCA1 modulates the sensitivity of ovarian cancer cells to auranofin. Here we report that BRCA1-depleted cells exhibited increased DNA double strand breaks (DSBs) and decreased clonogenic cell survival upon auranofin treatment. Interestingly, auranofin induced the expression of Nrf2 in BRCA1-depleted cells suggesting its regulation independent of BRCA1. Furthermore, anti-oxidant agent, N-acetyl cysteine (NAC) protected BRCA1-depleted cells from DNA damage and apoptosis induced by auranofin. Our study suggests that accumulated lethal DSBs resulting from the oxidative damage render BRCA1 deficient cells more sensitive to auranofin despite the activation of Nrf2.

  19. Soybean fermentation with Bacillus licheniformis increases insulin sensitizing and insulinotropic activity.

    Science.gov (United States)

    Yang, Hye Jeong; Kwon, Dae Young; Moon, Na Rang; Kim, Min Jung; Kang, Hee Joo; Jung, Do Yeon; Park, Sunmin

    2013-11-01

    Traditionally fermented soybeans (chungkookjang; TFC) may have potent anti-diabetic activity, depending on the ambient microorganisms and conditions. We hypothesized that one of the major Bacillus species in TFC contributes to the anti-diabetic activity and could be used to standardize a highly functional TFC. We tested the hypothesis by using cell-based studies to evaluate insulin sensitizing and insulinotropic action of chungkookjangs fermented with various Bacillus spp. and fermentation periods. The 70% methanol and water extracts of chungkookjang fermented with Bacillus licheniformis (BL) for 48 h contained similar profiles of isoflavonoids and peptides to methanol and water extracts of TFC with potent anti-diabetic activity. Water extracts (mainly containing peptides) of TFC and BL fermented for 48 h and 72 h had a better insulin sensitizing action via activating peroxisome proliferator-activated receptor-γ (PPAR-γ) and increased the expression of PPAR-γ in 3T3-L1 adipocytes better than unfermented cooked soybeans (CSB). The 70% methanol extracts (predominantly isoflavone aglycones) of BL fermented for 48 h and 72 h improved glucose-stimulated insulin secretion and protected β-cell viability better than CSB in insulinoma cells, and the improvement by BL was similar to TFC. In conclusion, the BL water extract fermented for 48 h exhibited equal insulin sensitization as TFC and BL methanol extract exerted similar insulinotropic actions to those of TFC. B. licheniformis may be one of the major microorganisms responsible for anti-diabetic actions of chungkookjang. It is important to make chungkookjang that retains the anti-diabetic properties of the most efficacious traditional chungkookjang using a standardized method.

  20. Increased sensitivity to cocaine-induced analgesia in Spontaneously Hypertensive Rats (SHR).

    Science.gov (United States)

    Pamplona, Fabrício A; Vendruscolo, Leandro F; Takahashi, Reinaldo N

    2007-02-13

    This study examined the analgesic effect of cocaine in Spontaneously Hypertensive Rats (SHR), which are considered a suitable model for the study of attention deficit hyperactivity disorder (ADHD), and in Wistar (WIS) rats of both sexes using the hot-plate test. In addition, we tested whether habituation to the unheated hot-plate apparatus, that "normalizes" the basal hypoalgesic phenotype of SHR, alters the subsequent cocaine-induced analgesia (CIA) in this strain. SHR of both sexes were hypoalgesic compared to WIS rats in the hot-plate test and showed higher sensitivity to CIA. Habituation to the unheated hot-plate reduced the basal nociceptive latency of SHR, suggesting cognitive/emotional modulation of pain in this strain, but did not alter the magnitude of CIA. The present study shows increased sensitivity to CIA in SHR, which may be related to abnormalities in the mesocorticolimbic dopaminergic system. Further studies using SHR strain may reveal new information on the neurobiological mechanisms underlying ADHD and its co-morbidity with drug addiction.

  1. Osteoblasts detect pericellular calcium concentration increase via neomycin-sensitive voltage gated calcium channels.

    Science.gov (United States)

    Sun, Xuanhao; Kishore, Vipuil; Fites, Kateri; Akkus, Ozan

    2012-11-01

    The mechanisms underlying the detection of critically loaded or micro-damaged regions of bone by bone cells are still a matter of debate. Our previous studies showed that calcium efflux originates from pre-failure regions of bone matrix and MC3T3-E1 osteoblasts respond to such efflux by an increase in the intracellular calcium concentration. The mechanisms by which the intracellular calcium concentration increases in response to an increase in the pericellular calcium concentration are unknown. Elevation of the intracellular calcium may occur via release from the internal calcium stores of the cell and/or via the membrane bound channels. The current study applied a wide range of pharmaceutical inhibitors to identify the calcium entry pathways involved in the process: internal calcium release from endoplasmic reticulum (ER, inhibited by thapsigargin and TMB-8), calcium receptor (CaSR, inhibited by calhex), stretch-activated calcium channel (SACC, inhibited by gadolinium), voltage-gated calcium channels (VGCC, inhibited by nifedipine, verapamil, neomycin, and ω-conotoxin), and calcium-induced-calcium-release channel (CICRC, inhibited by ryanodine and dantrolene). These inhibitors were screened for their effectiveness to block intracellular calcium increase by using a concentration gradient induced calcium efflux model which mimics calcium diffusion from the basal aspect of cells. The inhibitor(s) which reduced the intracellular calcium response was further tested on osteoblasts seeded on mechanically loaded notched cortical bone wafers undergoing damage. The results showed that only neomycin reduced the intracellular calcium response in osteoblasts, by 27%, upon extracellular calcium stimulus induced by concentration gradient. The inhibitory effect of neomycin was more pronounced (75% reduction in maximum fluorescence) for osteoblasts seeded on notched cortical bone wafers loaded mechanically to damaging load levels. These results imply that the increase in

  2. TIMP-1 gene deficiency increases tumour cell sensitivity to chemotherapy-induced apoptosis

    DEFF Research Database (Denmark)

    Davidsen, Marie Louise; Würts, S.Ø.; Rømer, Maria Unni Koefoed;

    2006-01-01

    in cancer. In this regard, several studies have demonstrated an antiapoptotic effect of TIMP-1 in a number of different cell types. Since chemotherapy works by inducing apoptosis in cancer cells, we raised the hypothesis that TIMP-1 promotes resistance against chemotherapeutic drugs. In order to investigate...... this hypothesis, we have established TIMP-1 gene-deficient and TIMP-1 wild-type fibrosarcoma cells from mouse lung tissue. We have characterised these cells with regard to TIMP-1 genotype, TIMP-1 expression, malignant transformation and sensitivity to chemotherapy-induced apoptosis. We show that TIMP-1 gene...... deficiency increases the response to chemotherapy considerably, confirming that TIMP-1 protects the cells from apoptosis. This is to our knowledge the first study investigating TIMP-1 and chemotherapy-induced apoptosis employing a powerful model system comprising TIMP-1 gene-deficient cells...

  3. Faster quantitative real-time PCR protocols may lose sensitivity and show increased variability.

    Science.gov (United States)

    Hilscher, Chelsey; Vahrson, Wolfgang; Dittmer, Dirk P

    2005-11-27

    Quantitative real-time PCR has become the method of choice for measuring mRNA transcription. Recently, fast PCR protocols have been developed as a means to increase assay throughput. Yet it is unclear whether more rapid cycling conditions preserve the original assay performance characteristics. We compared 16 primer sets directed against Epstein-Barr virus (EBV) mRNAs using universal and fast PCR cycling conditions. These primers are of clinical relevance, since they can be used to monitor viral oncogene and drug-resistance gene expression in transplant patients and EBV-associated cancers. While none of the primers failed under fast PCR conditions, the fast PCR protocols performed worse than universal cycling conditions. Fast PCR was associated with a loss of sensitivity as well as higher variability, but not with a loss of specificity or with a higher false positive rate.

  4. Increased BOLD sensitivity in the orbitofrontal cortex using slice-dependent echo times at 3 T.

    Science.gov (United States)

    Domsch, Sebastian; Linke, Julia; Heiler, Patrick M; Kroll, Alexander; Flor, Herta; Wessa, Michèle; Schad, Lothar R

    2013-02-01

    Functional magnetic resonance imaging (fMRI) exploits the blood oxygenation level dependent (BOLD) effect to detect neuronal activation related to various experimental paradigms. Some of these, such as reversal learning, involve the orbitofrontal cortex and its interaction with other brain regions like the amygdala, striatum or dorsolateral prefrontal cortex. These paradigms are commonly investigated with event-related methods and gradient echo-planar imaging (EPI) with short echo time of 27 ms. However, susceptibility-induced signal losses and image distortions in the orbitofrontal cortex are still a problem for this optimized sequence as this brain region consists of several slices with different optimal echo times. An EPI sequence with slice-dependent echo times is suitable to maximize BOLD sensitivity in all slices and might thus improve signal detection in the orbitofrontal cortex. To test this hypothesis, we first optimized echo times via BOLD sensitivity simulation. Second, we measured 12 healthy volunteers using a standard EPI sequence with an echo time of 27 ms and a modified EPI sequence with echo times ranging from 22 ms to 47 ms. In the orbitofrontal cortex, the number of activated voxels increased from 87 ± 44 to 549 ± 83 and the maximal t-value increased from 4.4 ± 0.3 to 5.4 ± 0.3 when the modified EPI was used. We conclude that an EPI with slice-dependent echo times may be a valuable tool to mitigate susceptibility artifacts in event-related whole-brain fMRI studies with a focus on the orbitofrontal cortex.

  5. Increased Replicative Fitness Can Lead to Decreased Drug Sensitivity of Hepatitis C Virus

    Science.gov (United States)

    Sheldon, Julie; Beach, Nathan M.; Moreno, Elena; Gallego, Isabel; Piñeiro, David; Martínez-Salas, Encarnación; Gregori, Josep; Quer, Josep; Esteban, Juan Ignacio; Rice, Charles M.

    2014-01-01

    ABSTRACT Passage of hepatitis C virus (HCV) in human hepatoma cells resulted in populations that displayed partial resistance to alpha interferon (IFN-α), telaprevir, daclatasvir, cyclosporine, and ribavirin, despite no prior exposure to these drugs. Mutant spectrum analyses and kinetics of virus production in the absence and presence of drugs indicate that resistance is not due to the presence of drug resistance mutations in the mutant spectrum of the initial or passaged populations but to increased replicative fitness acquired during passage. Fitness increases did not alter host factors that lead to shutoff of general host cell protein synthesis and preferential translation of HCV RNA. The results imply that viral replicative fitness is a mechanism of multidrug resistance in HCV. IMPORTANCE Viral drug resistance is usually attributed to the presence of amino acid substitutions in the protein targeted by the drug. In the present study with HCV, we show that high viral replicative fitness can confer a general drug resistance phenotype to the virus. The results exclude the possibility that genomes with drug resistance mutations are responsible for the observed phenotype. The fact that replicative fitness can be a determinant of multidrug resistance may explain why the virus is less sensitive to drug treatments in prolonged chronic HCV infections that favor increases in replicative fitness. PMID:25122776

  6. MiR-224 expression increases radiation sensitivity of glioblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Upraity, Shailendra; Kazi, Sadaf; Padul, Vijay; Shirsat, Neelam Vishwanath, E-mail: nshirsat@actrec.gov.in

    2014-05-30

    Highlights: • MiR-224 expression in established glioblastoma cell lines and sporadic tumor tissues is low. • Exogenous miR-224 expression was found to increase radiation sensitivity of glioblastoma cells. • MiR-224 expression brought about 55–60% reduction in API5 expression levels. • Transfection with API5 siRNA increased radiation sensitivity of glioblastoma cells. • Low miR-224 and high API5 expression correlated with worse survival of GBM patients. - Abstract: Glioblastoma (GBM) is the most common and highly aggressive primary malignant brain tumor. The intrinsic resistance of this brain tumor limits the efficacy of administered treatment like radiation therapy. In the present study, effect of miR-224 expression on growth characteristics of established GBM cell lines was analyzed. MiR-224 expression in the cell lines as well as in primary GBM tumor tissues was found to be low. Exogenous transient expression of miR-224 using either synthetic mimics or stable inducible expression using doxycycline inducible lentiviral vector carrying miR-224 gene, was found to bring about 30–55% reduction in clonogenic potential of U87 MG cells. MiR-224 expression reduced clonogenic potential of U87 MG cells by 85–90% on irradiation at a dose of 6 Gy, a dose that brought about 50% reduction in clonogenic potential in the absence of miR-224 expression. MiR-224 expression in glioblastoma cells resulted in 55–65% reduction in the expression levels of API5 gene, a known target of miR-224. Further, siRNA mediated down-regulation of API5 was also found to have radiation sensitizing effect on glioblastoma cell lines. Analysis of the Cancer Genome Atlas data showed lower miR-224 expression levels in male GBM patients to correlate with poorer survival. Higher expression levels of miR-224 target API5 also showed significant correlation with poorer survival of GBM patients. Up-regulation of miR-224 or down-regulation of its target API5 in combination with radiation therapy

  7. Peripheral Sensitization Increases Opioid Receptor Expression and Activation by Crotalphine in Rats

    Science.gov (United States)

    Zambelli, Vanessa Olzon; Fernandes, Ana Carolina de Oliveira; Gutierrez, Vanessa Pacciari; Ferreira, Julio Cesar Batista; Parada, Carlos Amilcar; Mochly-Rosen, Daria; Cury, Yara

    2014-01-01

    Inflammation enhances the peripheral analgesic efficacy of opioid drugs, but the mechanisms involved in this phenomenon have not been fully elucidated. Crotalphine (CRP), a peptide that was first isolated from South American rattlesnake C.d. terrificus venom, induces a potent and long-lasting anti-nociceptive effect that is mediated by the activation of peripheral opioid receptors. Because the high efficacy of CRP is only observed in the presence of inflammation, we aimed to elucidate the mechanisms involved in the CRP anti-nociceptive effect induced by inflammation. Using real-time RT-PCR, western blot analysis and ELISA assays, we demonstrate that the intraplantar injection of prostaglandin E2 (PGE2) increases the mRNA and protein levels of the µ- and κ-opioid receptors in the dorsal root ganglia (DRG) and paw tissue of rats within 3 h of the injection. Using conformation state-sensitive antibodies that recognize activated opioid receptors, we show that PGE2, alone does not increase the activation of these opioid receptors but that in the presence of PGE2, the activation of specific opioid receptors by CRP and selective µ- and κ-opioid receptor agonists (positive controls) increases. Furthermore, PGE2 down-regulated the expression and activation of the δ-opioid receptor. CRP increased the level of activated mitogen-activated protein kinases in cultured DRG neurons, and this increase was dependent on the activation of protein kinase Cζ. This CRP effect was much more prominent when the cells were pretreated with PGE2. These results indicate that the expression and activation of peripheral opioid receptors by opioid-like drugs can be up- or down-regulated in the presence of an acute injury and that acute tissue injury enhances the efficacy of peripheral opioids. PMID:24594607

  8. Addiction: Decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain’s control circuit

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Telang, F.; Baler, R.

    2010-07-01

    Based on brain imaging findings, we present a model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions. The dysfunctions reflect (a) decreased sensitivity of reward circuits, (b) enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and (c) negative mood, and a weakened control circuit. Although initial experimentation with a drug of abuse is largely a voluntary behavior, continued drug use can eventually impair neuronal circuits in the brain that are involved in free will, turning drug use into an automatic compulsive behavior. The ability of addictive drugs to co-opt neurotransmitter signals between neurons (including dopamine, glutamate, and GABA) modifies the function of different neuronal circuits, which begin to falter at different stages of an addiction trajectory. Upon exposure to the drug, drug cues or stress this results in unrestrained hyperactivation of the motivation/drive circuit that results in the compulsive drug intake that characterizes addiction.

  9. Salinomycin sensitizes antimitotic drugs-treated cancer cells by increasing apoptosis via the prevention of G2 arrest

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ju-Hwa; Yoo, Hye-In; Kang, Han Sung; Ro, Jungsil [Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do (Korea, Republic of); Yoon, Sungpil, E-mail: yoons@ncc.re.kr [Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do (Korea, Republic of)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Sal sensitizes antimitotic drugs-treated cancer cells. Black-Right-Pointing-Pointer Sal sensitizes them by prevention of G2 arrest and reduced cyclin D1 levels. Black-Right-Pointing-Pointer Sal also sensitizes them by increasing DNA damage and reducing p21 level. Black-Right-Pointing-Pointer A low concentration of Sal effectively sensitized the cancer cells to antimitotic drugs. -- Abstract: Here, we investigated whether Sal could sensitize cancer cells to antimitotic drugs. We demonstrated that Sal sensitized paclitaxcel (PAC)-, docetaxcel (DOC)-, vinblastin (VIN)-, or colchicine (COL)-treated cancer cell lines, suggesting that Sal has the ability to sensitize the cells to any form of microtubule-targeting drugs. Sensitization to the antimitotic drugs could be achieved with very low concentrations of Sal, suggesting that there is a possibility to minimize Sal toxicity associated with human cancer patient treatments. Sensitization by Sal increased apoptosis, which was observed by C-PARP production. Sal sensitized the cancer cells to antimitotic drugs by preventing G2 arrest, suggesting that Sal contributes to the induction of mitotic catastrophe. Sal generally reduced cyclin D1 levels in PAC-, DOC-, and VIN-treated cells. In addition, Sal treatment increased pH2AX levels and reduced p21 levels in antimitotic drugs-treated cells. These observations suggest that the mechanisms underlying Sal sensitization to DNA-damaging compounds, radiation, and microtubule-targeting drugs are similar. Our data demonstrated that Sal sensitizes cancer cells to antimitotic drugs by increasing apoptosis through the prevention of G2 arrest via conserved Sal-sensitization mechanisms. These results may contribute to the development of Sal-based chemotherapy for cancer patients treated with antimitotic drugs.

  10. Increased salt sensitivity induced by sensory denervation:role of superoxide

    Institute of Scientific and Technical Information of China (English)

    Wei-zhong SONG; Alex F CHEN; Donna H WANG

    2004-01-01

    AIM: To test the hypothesis that production of superoxide in mesenteric resistance arteries is increased and contributes to the development of hypertension induced by sensory denervation plus high salt intake. METHODS:Newborn Wistar rats were given capsaicin 50mg/kg sc on the 1st and 2nd d of life. After weaning, male rats were grouped as follows and treated for 3 weeks with: capsaicin pretreatment plus normal sodium diet (0.5%, CAP-NS),CAP plus high sodium diet (4%, CAP-HS), control plus NS (CON-NS), or CON-HS. Both tail-cuff systolic blood pressure and mean arterial pressure (MAP) were measured in each of the groups. Western blot analysis was used for measurement of manganese superoxide dismutase (MnSOD) and endothelial nitric oxide synthase (eNOS) in the mesenteric resistance arteries. Lucigenin chemiluminescence assay was used for superoxide production in the mesenteric resistance arteries. The Griess method was used for measurement of nitrite/nitrate levels in plasma.RESULTS: Both tail-cuff pressure and MAP were higher in CAP-HS compared with CAP-NS, CON-HS, and CONNS rats (P<0.05). Both MnSOD and eNOS in the mesenteric resistance arteries were increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P<0.05). However, nitrite/nitrate levels in plasma were not different among 4 groups. Acute iv administration of tempol, a membrane-permeable superoxide scavenger, decreased MAP in both CAP-HS and CON-HS when compared with their respective controls. However, the decreases of MAP between these two groups were not different. Chronic treatment with tempol failed to prevent the development of hypertension in CAP-HS rats. Superoxide production in the mesenteric resistance arteries was increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P<0.05). However, chronic treatment with tempol did not prevent the increase of mesenteric superoxide production in CAP-HS rats. CONCLUSIONS:Regardless of increased vascular MnSOD levels, salt sensitive hypertension

  11. The new horizon in 2D electrophoresis: new technology to increase resolution and sensitivity.

    Science.gov (United States)

    Moche, Martin; Albrecht, Dirk; Maaß, Sandra; Hecker, Michael; Westermeier, Reiner; Büttner, Knut

    2013-06-01

    A principally new type of an electrophoresis setup for the second dimension of 2DE named HPE (high performance electrophoresis) has recently become available that provides excellent reproducibility much superior to traditional 2DE. It takes up ideas from early beginnings of 2DE which could not be satisfactory realized at that time. The new HPE system is in contrast to all other established systems a horizontal electrophoresis that employs a new type of precast polyacrylamide gels on film-backing and runs on a multilevel flatbed electrophoresis apparatus. In a systematic approach we compared its features to traditional 2DE for the cytosolic proteome of Bacillus subtilis. Not only the reproducibility is enhanced, but also nearly all qualitative parameters as resolution, sensitivity, the number of protein spots (25% more), and the number of different proteins (also additional 25%) are markedly increased. More than 200 proteins were exclusively found in HPE. This new electrophoresis system does not use buffer tanks. No glass plates are needed. Therefore handling of gels is greatly facilitated and very simple to use even for personnel with low technical skills. The new HPE system is technically at the beginnings and further development with increased performance can be expected.

  12. IL-35 over-expression increases apoptosis sensitivity and suppresses cell growth in human cancer cells.

    Science.gov (United States)

    Long, Jun; Zhang, Xulong; Wen, Mingjie; Kong, Qingli; Lv, Zhe; An, Yunqing; Wei, Xiao-Qing

    2013-01-01

    Interleukin (IL)-35 is a novel heterodimeric cytokine in the IL-12 family and is composed of two subunits: Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35. IL-35 is expressed in T regulatory (Treg) cells and contributes to the immune suppression function of these cells. In contrast, we found that both IL-35 subunits were expressed concurrently in most human cancer cell lines compared to normal cell lines. In addition, we found that TNF-α and IFN-γ stimulation led to increased IL-35 expression in human cancer cells. Furthermore, over-expression of IL-35 in human cancer cells suppressed cell growth in vitro, induced cell cycle arrest at the G1 phase, and mediated robust apoptosis induced by serum starvation, TNF-α, and IFN-γ stimulation through the up-regulation of Fas and concurrent down-regulation of cyclinD1, survivin, and Bcl-2 expression. In conclusion, our results reveal a novel functional role for IL-35 in suppressing cancer activity, inhibiting cancer cell growth, and increasing the apoptosis sensitivity of human cancer cells through the regulation of genes related to the cell cycle and apoptosis. Thus, this research provides new insights into IL-35 function and presents a possible target for the development of novel cancer therapies.

  13. Offspring of prenatal IV nicotine exposure exhibit increased sensitivity to the reinforcing effects of methamphetamine

    Directory of Open Access Journals (Sweden)

    Steven Brown Harrod

    2012-06-01

    Full Text Available Maternal smoking during pregnancy is associated with increased substance abuse in offspring. Preclinical research shows that in utero exposure to nicotine, the primary psychoactive compound in tobacco smoke, influences the neurodevelopment of reward systems and alters motivated behavior in offspring. The present study determined if prenatal nicotine (PN exposure altered the sensitivity to the reinforcing and aversive effects of methamphetamine (METH in offspring using a low dose, intravenous (IV exposure method. Pregnant dams were administered nicotine (0.05 mg/kg/injection or prenatal saline (PS 3×/day on gestational days 8-21, and adult offspring were tested using METH self-administration (experiment 1 or METH-induced conditioned taste aversion (CTA; experiment 2 procedures. For METH self-administration, animals were trained to respond for IV METH (0.05 mg/kg/injection; fixed-ratio 3 and they were tested on varying doses the reinforcer (0.0005-1.0 mg/kg/injection. For METH CTA, rats received three saccharin and METH pairings (0, 0.3, or 0.5 mg/kg, sc followed by fourteen daily extinction trials. Experiment 1: PN and PS animals exhibited inverted U-shaped dose-response curves; however, the PN animal’s curve was shifted to the left, suggesting PN animals were more sensitive to the reinforcing effects of METH. Experiment 2: METH CTA was acquired in a dose-dependent manner and the factor of PN exposure was not related to the acquisition or extinction of METH-induced CTA. There were no sex differences in either experiment. These results indicate that adult offspring of IV PN exposure exhibited altered motivation for the reinforcing effects of METH. This suggests that PN exposure, via maternal smoking, will alter the reinforcing effects of METH during later stages of development, and furthermore, will influence substance use vulnerability in adult human offspring.

  14. Increased postexercise insulin sensitivity is accompanied by increased AS160 phosphorylation in slow-twitch soleus muscle.

    Science.gov (United States)

    Iwabe, Maiko; Kawamoto, Emi; Koshinaka, Keiichi; Kawanaka, Kentaro

    2014-12-01

    A single bout of exercise can enhance insulin-stimulated glucose uptake in both fast-twitch (type II) and slow-twitch (type I) skeletal muscle for several hours postexercise. Akt substrate of 160 kDa (AS160) is most distal insulin signaling proteins that have been proposed to contribute to the postexercise enhancement of insulin action in fast-twitch muscle. In this study, we examined whether the postexercise increase in insulin action of glucose uptake in slow-twitch muscle is accompanied by increased phosphorylation of AS160 and its paralog TBC1D1. Male Wistar rats (~1-month-old) were exercised on a treadmill for 180 min (9 m/min). Insulin (50 μU/mL)-stimulated glucose uptake was increased at 2 h after cessation of exercise in soleus muscle composed of predominantly slow-twitch fibers. This postexercise increase in insulin action of glucose uptake was accompanied by increased phosphorylation of AS160 (detected by phospho-Thr642 and phospho-Ser588 antibody). On the other hand, prior exercise did not increase phosphorylation of TBC1D1 (detected by phospho-Thr590) at 2 h postexercise. These results suggest the possibility that an enhancement in AS160 phosphorylation but not TBC1D1 phosphorylation is involved with increased postexercise insulin action of glucose uptake in slow-twitch muscle.

  15. Temperature modulates coccolithophorid sensitivity of growth, photosynthesis and calcification to increasing seawater pCO₂.

    Science.gov (United States)

    Sett, Scarlett; Bach, Lennart T; Schulz, Kai G; Koch-Klavsen, Signe; Lebrato, Mario; Riebesell, Ulf

    2014-01-01

    Increasing atmospheric CO₂ concentrations are expected to impact pelagic ecosystem functioning in the near future by driving ocean warming and acidification. While numerous studies have investigated impacts of rising temperature and seawater acidification on planktonic organisms separately, little is presently known on their combined effects. To test for possible synergistic effects we exposed two coccolithophore species, Emiliania huxleyi and Gephyrocapsa oceanica, to a CO₂ gradient ranging from ∼0.5-250 µmol kg⁻¹ (i.e. ∼20-6000 µatm pCO₂) at three different temperatures (i.e. 10, 15, 20°C for E. huxleyi and 15, 20, 25°C for G. oceanica). Both species showed CO₂-dependent optimum-curve responses for growth, photosynthesis and calcification rates at all temperatures. Increased temperature generally enhanced growth and production rates and modified sensitivities of metabolic processes to increasing CO₂. CO₂ optimum concentrations for growth, calcification, and organic carbon fixation rates were only marginally influenced from low to intermediate temperatures. However, there was a clear optimum shift towards higher CO₂ concentrations from intermediate to high temperatures in both species. Our results demonstrate that the CO₂ concentration where optimum growth, calcification and carbon fixation rates occur is modulated by temperature. Thus, the response of a coccolithophore strain to ocean acidification at a given temperature can be negative, neutral or positive depending on that strain's temperature optimum. This emphasizes that the cellular responses of coccolithophores to ocean acidification can only be judged accurately when interpreted in the proper eco-physiological context of a given strain or species. Addressing the synergistic effects of changing carbonate chemistry and temperature is an essential step when assessing the success of coccolithophores in the future ocean.

  16. Temperature modulates coccolithophorid sensitivity of growth, photosynthesis and calcification to increasing seawater pCO₂.

    Directory of Open Access Journals (Sweden)

    Scarlett Sett

    Full Text Available Increasing atmospheric CO₂ concentrations are expected to impact pelagic ecosystem functioning in the near future by driving ocean warming and acidification. While numerous studies have investigated impacts of rising temperature and seawater acidification on planktonic organisms separately, little is presently known on their combined effects. To test for possible synergistic effects we exposed two coccolithophore species, Emiliania huxleyi and Gephyrocapsa oceanica, to a CO₂ gradient ranging from ∼0.5-250 µmol kg⁻¹ (i.e. ∼20-6000 µatm pCO₂ at three different temperatures (i.e. 10, 15, 20°C for E. huxleyi and 15, 20, 25°C for G. oceanica. Both species showed CO₂-dependent optimum-curve responses for growth, photosynthesis and calcification rates at all temperatures. Increased temperature generally enhanced growth and production rates and modified sensitivities of metabolic processes to increasing CO₂. CO₂ optimum concentrations for growth, calcification, and organic carbon fixation rates were only marginally influenced from low to intermediate temperatures. However, there was a clear optimum shift towards higher CO₂ concentrations from intermediate to high temperatures in both species. Our results demonstrate that the CO₂ concentration where optimum growth, calcification and carbon fixation rates occur is modulated by temperature. Thus, the response of a coccolithophore strain to ocean acidification at a given temperature can be negative, neutral or positive depending on that strain's temperature optimum. This emphasizes that the cellular responses of coccolithophores to ocean acidification can only be judged accurately when interpreted in the proper eco-physiological context of a given strain or species. Addressing the synergistic effects of changing carbonate chemistry and temperature is an essential step when assessing the success of coccolithophores in the future ocean.

  17. Increased capsaicin-induced secondary hyperalgesia in patients with multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Holst, Helle; Arendt-Nielsen, Lars; Mosbech, Holger;

    2011-01-01

    in experimental pain models to provoke peripheral and central sensitization. In patients with symptoms elicited by odorous chemicals capsaicin-induced secondary hyperalgesia and temporal summation were assessed as markers for abnormal central nociceptive processing together with neurogenic inflammation (flare).......the underlying cause of pathophysiological mechanisms triggering multiple chemical sensitivity (MCS) remains disputed.Recently, alterations in the central nervous system, for example,central sensitization, similar to various chronic pain disorders, have been suggested. Capsaicin is used...

  18. Dysregulated autophagy increased melanocyte sensitivity to H2O2-induced oxidative stress in vitiligo

    Science.gov (United States)

    He, Yuanmin; Li, Shuli; Zhang, Weigang; Dai, Wei; Cui, Tingting; Wang, Gang; Gao, Tianwen; Li, Chunying

    2017-01-01

    In vitiligo, melanocytes are particularly vulnerable to oxidative stress owing to the pro-oxidant state generated during melanin synthesis and to the genetic antioxidant defects. Autophagy is a controlled self-digestion process which can protect cells against oxidative damage. However, the exact role of autophagy in vitiligo melanocytes in response to oxidative stress and the mechanism involved are still not clear. To determine the implications of autophagy for melanocyte survival in response to oxidative stress, we first detected the autophagic flux in normal melanocytes exposure to H2O2, and found that autophagy was significantly enhanced in normal melanocytes, for protecting cells against H2O2-induced oxidative damage. Nevertheless, vitiligo melanocytes exhibited dysregulated autophagy and hypersensitivity to H2O2-induced oxidative injury. In addition, we confirmed that the impairment of Nrf2-p62 pathway is responsible for the defects of autophagy in vitiligo melanocytes. Noteworthily, upregulation of the Nrf2-p62 pathway or p62 reduced H2O2-induced oxidative damage of vitiligo melanocytes. Therefore, our data demonstrated that dysregulated autophagy owing to the impairment of Nrf2-p62 pathway increase the sensitivity of vitiligo melanocytes to oxidative stress, thus promote the development of vitiligo. Upregulation of p62-dependent autophagy may be applied to vitiligo treatment in the future. PMID:28186139

  19. Increased bioassay sensitivity of bioactive molecule discovery using metal-enhanced bioluminescence

    Energy Technology Data Exchange (ETDEWEB)

    Golberg, Karina, E-mail: karingo@bgu.ac.il; Elbaz, Amit [Ben-Gurion University of the Negev, Avram and Stella Goldstein-Goren Department of Biotechnology Engineering (Israel); McNeil, Ronald [The Institute of Fluorescence, University of Maryland Baltimore County (United States); Kushmaro, Ariel [Ben-Gurion University of the Negev, Avram and Stella Goldstein-Goren Department of Biotechnology Engineering (Israel); Geddes, Chris D. [The Institute of Fluorescence, University of Maryland Baltimore County (United States); Marks, Robert S., E-mail: rsmarks@bgu.ac.il [Ben-Gurion University of the Negev, Avram and Stella Goldstein-Goren Department of Biotechnology Engineering (Israel)

    2014-12-15

    We report the use of bioluminescence signal enhancement via proximity to deposited silver nanoparticles for bioactive compound discovery. This approach employs a whole-cell bioreporter harboring a plasmid-borne fusion of a specific promoter incorporated with a bioluminescence reporter gene. The silver deposition process was first optimized to provide optimal nanoparticle size in the reaction time dependence with fluorescein. The use of silver deposition of 350 nm particles enabled the doubling of the bioluminescent signal amplitude by the bacterial bioreporter when compared to an untouched non-silver-deposited microtiter plate surface. This recording is carried out in the less optimal but necessary far-field distance. SEM micrographs provided a visualization of the proximity of the bioreporter to the silver nanoparticles. The electromagnetic field distributions around the nanoparticles were simulated using Finite Difference Time Domain, further suggesting a re-excitation of non-chemically excited bioluminescence in addition to metal-enhanced bioluminescence. The possibility of an antiseptic silver effect caused by such a close proximity was eliminated disregarded by the dynamic growth curves of the bioreporter strains as seen using viability staining. As a highly attractive biotechnology tool, this silver deposition technique, coupled with whole-cell sensing, enables increased bioluminescence sensitivity, making it especially useful for cases in which reporter luminescence signals are very weak.

  20. Selective ALDH3A1 inhibition by benzimidazole analogues increase mafosfamide sensitivity in cancer cells.

    Science.gov (United States)

    Parajuli, Bibek; Fishel, Melissa L; Hurley, Thomas D

    2014-01-23

    Aldehyde dehydrogenase enzymes irreversibly oxidize aldehydes generated from metabolism of amino acids, fatty acids, food, smoke, additives, and xenobiotic drugs. Cyclophosphamide is one such xenobiotic used in cancer therapies. Upon activation, cyclophosphamide forms an intermediate, aldophosphamide, which can be detoxified to carboxyphosphamide by aldehyde dehydrogenases (ALDH), especially ALDH1A1 and ALDH3A1. Consequently, selective inhibition of ALDH3A1 could increase chemosensitivity toward cyclophosphamide in ALDH3A1 expressing tumors. Here, we report detailed kinetics and structural characterization of a highly selective submicromolar inhibitor of ALDH3A1, 1-[(4-fluorophenyl)sulfonyl]-2-methyl-1H-benzimidazole (CB7, IC50 of 0.2 μM). CB7 does not inhibit ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, or ALDH2 activity. Structural, kinetics, and mutagenesis studies show that CB7 binds to the aldehyde binding pocket of ALDH3A1. ALDH3A1-expressing lung adenocarcinoma and glioblastoma cell lines are sensitized toward mafosfamide (MF) treatment in the presence analogues of CB7, whereas primary lung fibroblasts lacking ALDH3A1 expression, are not.

  1. Assessing the sensitivity of human skin hyperspectral responses to increasing anemia severity levels

    Science.gov (United States)

    Baranoski, Gladimir V. G.; Dey, Ankita; Chen, Tenn F.

    2015-09-01

    Anemia is a prevalent medical condition that seriously affects millions of people all over the world. In many regions, not only its initial detection but also its monitoring are hindered by limited access to laboratory facilities. This situation has motivated the development of a wide range of optical devices and procedures to assist physicians in these tasks. Although noticeable progress has been achieved in this area, the search for reliable, low-cost, and risk-free solutions still continues, and the strengthening of the knowledge base about this disorder and its effects is essential for the success of these initiatives. We contribute to these efforts by closely examining the sensitivity of human skin hyperspectral responses (within and outside the visible region of the light spectrum) to reduced hemoglobin concentrations associated with increasing anemia severity levels. This investigation, which involves skin specimens with distinct biophysical and morphological characteristics, is supported by controlled in silico experiments performed using a predictive light transport model and measured data reported in the biomedical literature. We also propose a noninvasive procedure to be employed in the monitoring of this condition at the point-of-care.

  2. Transformation of adrenal medullary chromaffin cells increases asthmatic susceptibility in pups from allergen-sensitized rats

    Directory of Open Access Journals (Sweden)

    Feng Jun-Tao

    2012-11-01

    Full Text Available Abstract Background Studies have shown that epinephrine release is impaired in patients with asthma. The pregnancy of female rats (dams with asthma promotes in their pups the differentiation of adrenal medulla chromaffin cells (AMCCs into sympathetic neurons, mediated by nerve growth factor, which leads to a reduction in epinephrine secretion. However, the relatedness between the alteration of AMCCs and increased asthma susceptibility in such offspring has not been established. Methods In this study, we observed the effects of allergization via ovalbumin on rat pups born of asthmatic dams. Results Compared to the offspring of untreated controls, bronchial hyperreactivity and airway inflammation were more severe in the pups from sensitized (asthmatic dams. In pups exposed to nerve growth factor (NGF in utero these effects were aggravated further, but the effects were blocked in pups whose dams had been treated with anti-NGF. Furthermore, alterations in AMCC phenotype corresponded to the degree of bronchial hyperreactivity and lung lesions of the different treatment groups. Such AMCC alterations included degranulation of chromaffin granules, reduction of epinephrine and phenylethanolamine-n-methyl transferase, and elevation of NGF and peripherin levels. Conclusions Our results present evidence that asthma during the pregnancy of rat dams promotes asthma susceptibility in their offspring, and that the transformation of AMCCs to neurons induced by NGF plays an important role in this process.

  3. Increased bioassay sensitivity of bioactive molecule discovery using metal-enhanced bioluminescence

    Science.gov (United States)

    Golberg, Karina; Elbaz, Amit; McNeil, Ronald; Kushmaro, Ariel; Geddes, Chris D.; Marks, Robert S.

    2014-12-01

    We report the use of bioluminescence signal enhancement via proximity to deposited silver nanoparticles for bioactive compound discovery. This approach employs a whole-cell bioreporter harboring a plasmid-borne fusion of a specific promoter incorporated with a bioluminescence reporter gene. The silver deposition process was first optimized to provide optimal nanoparticle size in the reaction time dependence with fluorescein. The use of silver deposition of 350 nm particles enabled the doubling of the bioluminescent signal amplitude by the bacterial bioreporter when compared to an untouched non-silver-deposited microtiter plate surface. This recording is carried out in the less optimal but necessary far-field distance. SEM micrographs provided a visualization of the proximity of the bioreporter to the silver nanoparticles. The electromagnetic field distributions around the nanoparticles were simulated using Finite Difference Time Domain, further suggesting a re-excitation of non-chemically excited bioluminescence in addition to metal-enhanced bioluminescence. The possibility of an antiseptic silver effect caused by such a close proximity was eliminated disregarded by the dynamic growth curves of the bioreporter strains as seen using viability staining. As a highly attractive biotechnology tool, this silver deposition technique, coupled with whole-cell sensing, enables increased bioluminescence sensitivity, making it especially useful for cases in which reporter luminescence signals are very weak.

  4. Parkinson's disease: low-dose haloperidol increases dopamine receptor sensitivity and clinical response.

    Science.gov (United States)

    Hudson, Craig J; Seeman, Philip; Seeman, Mary V

    2014-01-01

    Background. It is known that ultra-low doses of haloperidol can cause dopamine supersensitivity of dopamine D2 receptors and related behaviour in animals. Objective. The objective was to determine whether a daily ultra-low dose of 40 micrograms of haloperidol could enhance the clinical action of levodopa in Parkinson's disease patients. Method. While continuing their daily treatment with levodopa, 16 patients with Parkinson's disease were followed weekly for six weeks. They received an add-on daily dose of 40 micrograms of haloperidol for the first two weeks only. The SPES/SCOPA scale (short scale for assessment of motor impairments and disabilities in Parkinson's disease) was administered before treatment and weekly throughout the trial. Results. The results showed a mean decrease in SPES/SCOPA scores after one week of the add-on treatment. Conclusion. SCOPA scores decreased after the addition of low-dose haloperidol to the standard daily levodopa dose. This finding is consistent with an increase in sensitivity of dopamine D2 receptors induced by haloperidol. Such treatment for Parkinson's disease may possibly permit the levodopa dose to be reduced and, thus, delay the onset of levodopa side effects.

  5. Extension of Drosophila lifespan by Rosa damascena associated with an increased sensitivity to heat.

    Science.gov (United States)

    Schriner, Samuel E; Katoozi, Niki S; Pham, Kevin Q; Gazarian, Maral; Zarban, Asghar; Jafari, Mahtab

    2012-04-01

    Rosa damascena, or Damask rose, is a rose hybrid commonly harvested for rose oil used in perfumery and for rose water used to flavor food. The petal extract of R. damascena was recently found to decrease Drosophila melanogaster mortality without impairing reproductive fitness or metabolic rate. Here, we report that R. damascena extended both mean and maximum lifespan of the fly. The extract also protected against oxidative stress in flies, predominantly in females. However, it did not alter mitochondrial respiration or content, superoxide production, or the major antioxidant defenses, superoxide dismutase and catalase. The extract increased survival in both sexes when exposed to reduced iron, though surprisingly, it sensitized both sexes to heat stress (survival at 37°C), and appeared to down-regulate the major heat shock protein HSP70 and the small mitochondrial heat shock protein HSP22, at 25°C and after heat shock (4 h at 37°C). We hypothesize that R. damascena extends lifespan by protecting against iron, which concomitantly leads to decreased HSP expression and compromising heat tolerance.

  6. Increasing sensitivity of pulse EPR experiments using echo train detection schemes

    Science.gov (United States)

    Mentink-Vigier, F.; Collauto, A.; Feintuch, A.; Kaminker, I.; Tarle, V.; Goldfarb, D.

    2013-11-01

    Modern pulse EPR experiments are routinely used to study the structural features of paramagnetic centers. They are usually performed at low temperatures, where relaxation times are long and polarization is high, to achieve a sufficient Signal/Noise Ratio (SNR). However, when working with samples whose amount and/or concentration are limited, sensitivity becomes an issue and therefore measurements may require a significant accumulation time, up to 12 h or more. As the detection scheme of practically all pulse EPR sequences is based on the integration of a spin echo - either primary, stimulated or refocused - a considerable increase in SNR can be obtained by replacing the single echo detection scheme by a train of echoes. All these echoes, generated by Carr-Purcell type sequences, are integrated and summed together to improve the SNR. This scheme is commonly used in NMR and here we demonstrate its applicability to a number of frequently used pulse EPR experiments: Echo-Detected EPR, Davies and Mims ENDOR (Electron-Nuclear Double Resonance), DEER (Electron-Electron Double Resonance|) and EDNMR (Electron-Electron Double Resonance (ELDOR)-Detected NMR), which were combined with a Carr-Purcell-Meiboom-Gill (CPMG) type detection scheme at W-band. By collecting the transient signal and integrating a number of refocused echoes, this detection scheme yielded a 1.6-5 folds SNR improvement, depending on the paramagnetic center and the pulse sequence applied. This improvement is achieved while keeping the experimental time constant and it does not introduce signal distortion.

  7. 2-bromoethylamine, a suicide inhibitor of semicarbazide-sensitive amine oxidase, increases hydralazine hypotension in rats.

    Science.gov (United States)

    Vidrio, Horacio; Medina, Martha

    2005-09-01

    Previous work has shown that inhibitors of the predominantly vascular enzyme semicarbazide-sensitive amine oxidase (SSAO) potentiate the hypotensive response to hydralazine, itself a SSAO inhibitor, in anesthetized rats. The present study was carried out to determine whether the recently described suicide SSAO inhibitor 2-bromoethylamine shares this effect. Hypotensive responses to hydralazine, 0.1 mg/kg IV, were obtained in chloralose-urethane-anesthetized rats, either unpretreated or receiving bromoethylamine at different doses and pretreatment intervals. Parallel experiments were run with semicarbazide, the prototypical hydrazine SSAO inhibitor. Both inhibitors potentiated hydralazine hypotension, bromoethylamine having a longer latency and a shorter duration of action than semicarbazide. High doses of bromoethylamine did not produce potentiation, a phenomenon attributed to SSAO inactivation by excess substrate and decreased formation by the enzyme of the inhibitor product. Experiments with combined administration of both inhibitors were also carried out. When semicarbazide was administered before bromoethylamine, potentiaton was prevented, apparently by a mechanism similar to the above; when it was given after the amine, potentiation was increased. This was attributed to enzyme inhibition by interaction with 2 different active sites. The charactertistics of hydralazine potentiation by bromoethylamine were considered compatible with the mechanism of SSAO inhibition by the amine.

  8. Inhibition of PI3K increases oxaliplatin sensitivity in cholangiocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Udomchaiprasertkul Wandee

    2009-01-01

    Full Text Available Abstract Background Resistance of cholangiocarcinoma to chemotherapy is a major problem in cancer treatment. The mechanism of resistance is believed to involve phosphoinositide-3- kinase (PI3K/Akt activation. Although the platinum-containing compound oxaliplatin has been extensively used in the treatment of several solid tumors, recent data regarding its use to treat cholangiocarcinoma are ambiguous. Oxaliplatin resistance in this disease could potentially involve PI3K pathways. We, therefore, examined the effects of PI3K pathways in cholangiocarcinoma cells in modulating oxaliplatin resistance. Results After exposing the cholangiocarcinoma cell lines RMCCA1 and KKU100 to oxaliplatin, the levels of Akt and mTOR phosphorylation increased, as shown by western blot analysis. The WST-1 cell proliferation assay showed increased inhibition of cell growth under high concentrations of oxaliplatin. The combination of oxaliplatin with LY294002, an inhibitor of PI3K, resulted in a remarkable arrest of cell proliferation. Deactivation of mTOR by RAD001 was also synergistic with oxaliplatin, although to a lesser extent. The combination of oxaliplatin and a PI3K inhibitor also resulted in a significant induction of apoptosis, as demonstrated by the TUNEL assay. Conclusion Activation of PI3K might protect cholangiocarcinoma cells from oxaliplatininduced cytotoxicity. Although the inhibition of PI3K and the inhibition of mTOR both enhance oxaliplatin-induced cytotoxicity, PI3K inhibition has a greater effect. Targeting the PI3K pathway may be a useful approach to improve the chemotherapeutic sensitivity of cholangiocarcinoma.

  9. Developing teacher sensitivity to individual learning differences (ILDs) : Studies on increasing teacher effectiveness

    NARCIS (Netherlands)

    Rosenfeld, M.N.

    2008-01-01

    Effective teachers are sensitive to individual learning differences (ILDs). This dissertation investigates teacher changes as a result of eight long-term professional development (PD) courses (56-hours and 28-hours) designed to help them become more sensitive to ILDs. In these courses, the teache

  10. A genetic variant near the PMAIP1/Noxa gene is associated with increased bleomycin sensitivity

    NARCIS (Netherlands)

    Gu, J.; Ye, Y.; Spitz, M.R.; Lin, J.; Kiemeney, L.A.L.M.; Xing, J.; Hildebrandt, M.A.T.; Ki Hong, W.; Amos, C.I.; Wu, X.

    2011-01-01

    Mutagen sensitivity, a measurement of chromatid breaks induced by various mutagens in short-term cultures of peripheral blood lymphocytes, is an established risk factor for a number of cancers and is highly heritable. The purpose of this study is to identify genetic predictors of mutagen sensitivity

  11. Rock-dwelling lizards exhibit less sensitivity of sprint speed to increases in substrate rugosity.

    Science.gov (United States)

    Collins, Clint E; Self, Jessica D; Anderson, Roger A; McBrayer, Lance D

    2013-06-01

    Effectively moving across variable substrates is important to all terrestrial animals. The effects of substrates on lizard performance have ecological ramifications including the partitioning of habitat according to sprinting ability on different surfaces. This phenomenon is known as sprint sensitivity, or the decrease in sprint speed due to change in substrate. However, sprint sensitivity has been characterized only in arboreal Anolis lizards. Our study measured sensitivity to substrate rugosity among six lizard species that occupy rocky, sandy, and/or arboreal habitats. Lizards that use rocky habitats are less sensitive to changes in substrate rugosity, followed by arboreal lizards, and then by lizards that use sandy habitats. We infer from comparative phylogenetic analysis that forelimb, chest, and tail dimensions are important external morphological features related to sensitivity to changes in substrate rugosity.

  12. Increasing the selectivity and sensitivity of gas sensors for the detection of explosives

    Science.gov (United States)

    Mallin, Daniel

    Over the past decade, the use of improvised explosive devices (IEDs) has increased, domestically and internationally, highlighting a growing need for a method to quickly and reliably detect explosive devices in both military and civilian environments before the explosive can cause damage. Conventional techniques have been successful in explosive detection, however they typically suffer from enormous costs in capital equipment and maintenance, costs in energy consumption, sampling, operational related expenses, and lack of continuous and real-time monitoring. The goal was thus to produce an inexpensive, portable sensor that continuously monitors the environment, quickly detects the presence of explosive compounds and alerts the user. In 2012, here at URI, a sensor design was proposed for the detection of triacetone triperoxide (TATP). The design entailed a thermodynamic gas sensor that measures the heat of decomposition between trace TATP vapor and a metal oxide catalyst film. The sensor was able to detect TATP vapor at the part per million level (ppm) and showed great promise for eventual commercial use, however, the sensor lacked selectivity. Thus, the specific objective of this work was to take the original sensor design proposed in 2012 and to make several key improvements to advance the sensor towards commercialization. It was demonstrated that a sensor can be engineered to detect TATP and ignore the effects of interferent H2O2 molecules by doping SnO2 films with varying amounts of Pd. Compared with a pure SnO2 catalyst, a SnO2, film doped with 8 wt. % Pd had the highest selectivity between TATP and H2O2. Also, at 12 wt. % Pd, the response to TATP and H2O2 was enhanced, indicating that sensitivity, not only selectivity, can be increased by modifying the composition of the catalyst. An orthogonal detection system was demonstrated. The platform consists of two independent sensing mechanisms, one thermodynamic and one conductometric, which take measurements from

  13. Increased postexercise insulin sensitivity is accompanied by increased AS160 phosphorylation in slow‐twitch soleus muscle

    OpenAIRE

    Iwabe, Maiko; Kawamoto, Emi; Koshinaka, Keiichi; Kawanaka, Kentaro

    2014-01-01

    Abstract A single bout of exercise can enhance insulin‐stimulated glucose uptake in both fast‐twitch (type II) and slow‐twitch (type I) skeletal muscle for several hours postexercise. Akt substrate of 160 kDa (AS160) is most distal insulin signaling proteins that have been proposed to contribute to the postexercise enhancement of insulin action in fast‐twitch muscle. In this study, we examined whether the postexercise increase in insulin action of glucose uptake in slow‐twitch muscle is accom...

  14. Increased sensitivity of estrogen receptor alpha overexpressing antral follicles to methoxychlor and its metabolites.

    Science.gov (United States)

    Paulose, Tessie; Hernández-Ochoa, Isabel; Basavarajappa, Mallikarjuna S; Peretz, Jackye; Flaws, Jodi A

    2011-04-01

    Methoxychlor (MXC), an organochlorine pesticide, and its metabolites, mono-hydroxy MXC (MOH) and bis-hydroxy MXC (HPTE) are known ovarian toxicants and can cause inhibition of antral follicle growth. Since these chemicals bind to estrogen receptor alpha (ESR1), we hypothesized that ovaries overexpressing ESR1 (ESR1 OE) would be more susceptible to toxicity induced by MXC and its metabolites because the chemicals can bind to more ESR1 in the antral follicles. We cultured antral follicles from controls and ESR1 OE mouse ovaries with either the vehicle dimethylsulfoxide (DMSO), MXC, MOH, or HPTE. The data show that at 96 h, the cultured antral follicles from ESR1 OE antral follicles are more susceptible to toxicity induced by MXC, MOH, and HPTE because low doses of these chemicals cause follicle growth inhibition in ESR1 OE mice but not in control mice. On comparing gene expression levels of nuclear receptors in the cultured antral follicles of ESR1 OE and control follicles, we found differential messenger RNA (mRNA) expression of Esr1, estrogen receptor beta (Esr2), androgen receptor (Ar), progesterone receptor (Pr), and aryl hydrocarbon receptor (Ahr) between the genotypes. We also analyzed mRNA levels of Cyp3a41a, the enzyme metabolizing MOH and HPTE, in the cultured follicles and found that Cyp3a41a was significantly lower in DMSO-treated ESR1 OE follicles compared with controls. In ESR1 OE livers, we found that Cyp3a41a levels were significantly lower compared with control livers. Collectively, these data suggest that MXC and its metabolites cause differential gene expression in ESR1 OE mice compared with controls. The results also suggest that the increased sensitivity of ESR1 OE mouse ovaries to toxicity induced by MXC and its metabolites is due to low clearance of the metabolites by the liver and ovary.

  15. High Dose Astaxanthin Lowers Blood Pressure and Increases Insulin Sensitivity in Rats: Are These Effects Interdependent?

    Directory of Open Access Journals (Sweden)

    Harry G. Preuss, Bobby Echard, Eiji Yamashita, Nicholas V. Perricone

    2011-01-01

    Full Text Available The present investigation in Sprague-Dawley rats (SD was designed to examine effects of astaxanthin (Asta at different doses on elevated blood pressure (BP and glucose-insulin perturbations produced by heavy sucrose ingestion. We also examined effects of Asta on BP during restraint stress. SD were divided into six groups each containing eight rats. All SD ate a basic diet of ground regular rat chow with sucrose added at 30% w/w. The Control group received only the basic diet containing added sucrose, while the other five groups each received the same diet with added test material: captopril, (30 mg/Kg, pioglitazone (15.0 mg/Kg, low Asta (25 mg/Kg, medium Asta (50 mg/kg or high Asta (100 mg/Kg. Many tests were carried out to examine the mechanisms behind the effects of Asta on BP (serum ACE activity, losartan challenge, and LNAME challenge and the glucose-insulin system (glucose tolerance, HOMA measurement, and insulin challenge. In SD, a relatively low dose of Asta decreased SBP, but produced no major changes in the glucose-insulin system simulating results from a previous study using Zucker Fatty Rats. Increasing the dose of Asta resulted in both a lowering of elevated systolic BP and enhanced insulin sensitivity determined by many different estimations. BP lowering was consistent with changes in the renin-angiotensin (RAS and nitric oxide (NO systems. At the examined doses of each, captopril lowered BP in SD without influencing glucose-insulin metabolism, whereas pioglitazone favorably affected glucose-insulin metabolism while showing essentially no effects on BP. Accordingly, Asta beneficially affects both sucrose-induced elevations of BP and insulin resistance at relatively high doses in SD. Also, Asta at higher doses lessens restraint stress, whereas, captopril and pioglitazone did not at the doses examined, even though they influenced the BP and glucose-insulin systems respectively.

  16. Comparison of increased venous contrast in ischemic stroke using phase-sensitive MR imaging with perfusion changes on flow-sensitive alternating inversion recovery at 3 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Eijiro; Kanasaki, Yoshiko; Fujii, Shinya; Ogawa, Toshihide (Div. of Radiology, Dept. of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori Univ. Hospital, Yonago, Tottori (Japan)), email: eyamashi-ttr@umin.ac.jp; Tanaka, Takuro; Hirata, Yoshiharu (Div. of Clinical Radiology, Tottori Univ. Hospital, Yonago, Tottori (Japan))

    2011-10-15

    Background Increased venous contrast in ischemic stroke using susceptibility-weighted imaging has been widely reported, although few reports have compared increased venous contrast areas with perfusion change areas. Purpose To compare venous contrast on phase-sensitive MR images (PSI) with perfusion change on flow-sensitive alternating inversion recovery (FAIR) images, and to discuss the clinical use of PSI in ischemic stroke. Material and Methods Thirty patients with clinically suspected acute infarction of the middle cerebral artery (MCA) territory within 7 days of onset were evaluated. Phase-sensitive imaging (PSI), flow-sensitive alternating inversion recovery (FAIR), diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA) were obtained using 3 Tesla scanner. Two neuroradiologists independently reviewed the MR images, as well as the PSI, DWI, and FAIR images. They were blinded to the clinical data and to each other's findings. The abnormal area of each image was ultimately identified after both neuroradiologists reached consensus. We analyzed areas of increased venous contrast on PSI, perfusion changes on FAIR images and signal changes on DWI for each case. Results Venous contrast increased on PSI and hypoperfusion was evident on FAIR images from 22 of the 30 patients (73%). The distribution of the increased venous contrast was the same as that of the hypoperfused areas on FAIR images in 16 of these 22. The extent of these lesions was larger than that of lesions visualized by on DWI in 18 of the 22 patients. Hypointense signals reflecting hemorrhage and no increased venous contrast on PSI and hyperperfusion on FAIR images were found in six of the remaining eight patients (20%). Findings on PSI were normal and hypoperfusion areas were absent on FAIR images of two patients (7%). Conclusion Increased venous contrast on PSI might serve as an index of misery perfusion and provide useful information

  17. Increased brain dopamine D4-like binding after chronic ethanol is not associated with behavioral sensitization in mice.

    Science.gov (United States)

    Quadros, Isabel Marian Hartmann; Nobrega, Jose Nascimento; Hipolide, Debora Cristina; Souza-Formigoni, Maria Lucia Oliveira

    2005-10-01

    Dopaminergic D4 receptors have been hypothesized to be involved in neuropsychiatric disorders and substance abuse. In mice, repeated ethanol administration may induce behavioral sensitization, a phenomenon of increased sensitivity to the drug's stimulant properties. This study aimed to analyze brain D4 receptors binding in mice with different levels of behavioral sensitization to ethanol. Male Swiss mice received 2.2 g/kg ethanol (n = 64) or saline (n = 16) intraperitoneally daily for 21 days and were weekly tested for locomotor activity and for blood ethanol levels. According to the locomotor scores presented across test days, ethanol-treated mice were classified as "sensitized" or "nonsensitized." Twenty-four hours after the last administration, mice were sacrificed and brains were processed for autoradiography. Brain D4 binding was assessed by quantitative autoradiography using [3H]nemonapride + raclopride in three groups: saline-treated controls (n = 10), ethanol-sensitized (n = 11), and ethanol-nonsensitized (n = 9) mice. Both sensitized and nonsensitized mice showed higher D4 binding densities than saline-treated controls in the posterior caudate-putamen and the olfactory tubercle (p < .02), but only sensitized mice presented higher D4 binding than controls at the lateral septal nucleus (p < .02). However, there were no differences between sensitized and nonsensitized mice in any of the brain regions analyzed. Furthermore, sensitized and nonsensitized mice presented similar blood ethanol levels during the treatment. The higher D4 binding levels observed in both ethanol-treated subgroups (sensitized and nonsensitized) suggest that chronic ethanol treatment may induce upregulation of D4 receptors in specific brain regions. However, this mechanism does not seem to be associated with the differential ability to develop behavioral sensitization to ethanol in mice.

  18. Doping of a dielectric layer as a new alternative for increasing sensitivity of the contactless conductivity detection in microchips.

    Science.gov (United States)

    Lima, Renato Sousa; Segato, Thiago Pinotti; Gobbi, Angelo Luiz; Coltro, Wendell Karlos Tomazelli; Carrilho, Emanuel

    2011-12-21

    This communication describes a new procedure to increase the sensitivity of C(4)D in PDMS/glass microchips. The method consists in doping the insulating layer (PDMS) over the electrodes with nanoparticles of TiO(2), increasing thus its dielectric constant. The experimental protocol is simple, inexpensive, and fast.

  19. Nitric oxide (NO) inhibits antigen-stimulated increases in vasoconstriction and glycogenolysis in perfused livers derived from sensitized rats

    Energy Technology Data Exchange (ETDEWEB)

    Hines, K.L.; Bates, J.N.; Fisher, R.A. (Univ. of Iowa, Iowa City (United States))

    1991-03-11

    Recent studies in the authors laboratory demonstrated that infusion of antigen into perfused livers from sensitized rats produces increases in hepatic portal pressure, increases in hepatic glucose output and decreases in hepatic oxygen consumption. In the present study, effects of NO on these hepatic responses to antigen challenge were investigated. Infusion of NO into perfused livers from sensitized rats attenuated ovalbumin induced increases in hepatic portal pressure and glucose output approximately 85% and 90%, respectively, and abolished ovalbumin-induced decreases in hepatic oxygen consumption. The duration of ovalbumin-stimulated increases in hepatic portal pressure was reduced nearly 90% by NO. Similarly, infusion of NO into perfused livers from sensitized rats inhibited increases in hepatic portal pressure and glucose output in response to platelet-activating factor (PAF) nearly 80 and 90%, respectively. In contrast, NO inhibited completely hepatic vasoconstriction in response to phenylephrine without altering glycogenolytic responses to this {alpha}-adrenergic agonist. These results provide evidence for regulatory effects of NO on hemodynamic and glycogenolytic responses to antigen in perfused livers from sensitized rats. These observations support previous findings which suggest that hepatic responses to sensitizing antigen may be mediated by PAF or other autacoid mediators which stimulate glycogenolysis in liver by indirect mechanisms involving hepatic vasoconstriction.

  20. Anxiety sensitivity uniquely predicts exercise behaviors in young adults seeking to increase physical activity

    NARCIS (Netherlands)

    Moshier, S.J.; Szuhany, K.L.; Hearon, B.A.; Smits, J.A.J.; Otto, M.W.

    2016-01-01

    Individuals with elevated levels of anxiety sensitivity (AS) may be motivated to avoid aversive emotional or physical states, and therefore may have greater difficulty achieving healthy behavioral change. This may be particularly true for exercise, which produces many of the somatic sensations withi

  1. Infection with Soil-Transmitted Helminths Is Associated with Increased Insulin Sensitivity

    NARCIS (Netherlands)

    Wiria, A.E.; Hamid, F.; Wammes, L.J.; Prasetyani, M.A.; Dekkers, O.M.; May, L.; Kaisar, M.M.; Verweij, J.J.; Guigas, B.; Partono, F.; Sartono, E.; Supali, T.; Yazdanbakhsh, M.; Smit, J.W.A.

    2015-01-01

    OBJECTIVE: Given that helminth infections have been shown to improve insulin sensitivity in animal studies, which may be explained by beneficial effects on energy balance or by a shift in the immune system to an anti-inflammatory profile, we investigated whether soil-transmitted helminth (STH)-infec

  2. Aerobic Exercise Increases Peripheral and Hepatic Insulin Sensitivity in Sedentary Adolescents

    NARCIS (Netherlands)

    van der Heijden, Gert-Jan; Toffolo, Gianna; Manesso, Erica; Sauer, Pieter J. J.; Sunehag, Agneta L.

    2009-01-01

    Context: Data are limited on the effects of controlled aerobic exercise programs (without weight loss) on insulin sensitivity and glucose metabolism in children and adolescents. Objective: To determine whether a controlled aerobic exercise program (without weight loss) improves peripheral and hepati

  3. University Practice as a Key Factor in Increasing the Sensitivity to Educational Inclusion

    Science.gov (United States)

    De Luna Velasco, Laura E.; Hernández Fernández, Antonio; Ferrándiz Vindel, Isabel María

    2012-01-01

    The present article is based on research carried out in three universities, the University Center South (Cusur, Mexico), Jaen and Cuenca (Spain) on the influence of university practice in the development of sensitivity towards inclusive education in our students the first years of the Diploma in Education, using the subject "pedagogical basis…

  4. Mutations in troponin T associated with Hypertrophic Cardiomyopathy increase Ca(2+)-sensitivity and suppress the modulation of Ca(2+)-sensitivity by troponin I phosphorylation.

    Science.gov (United States)

    Messer, Andrew E; Bayliss, Christopher R; El-Mezgueldi, Mohammed; Redwood, Charles S; Ward, Douglas G; Leung, Man-Ching; Papadaki, Maria; Dos Remedios, Cristobal; Marston, Steven B

    2016-07-01

    We investigated the effect of 7 Hypertrophic Cardiomyopathy (HCM)-causing mutations in troponin T (TnT) on troponin function in thin filaments reconstituted with actin and human cardiac tropomyosin. We used the quantitative in vitro motility assay to study Ca(2+)-regulation of unloaded movement and its modulation by troponin I phosphorylation. Troponin from a patient with the K280N TnT mutation showed no difference in Ca(2+)-sensitivity when compared with donor heart troponin and the Ca(2+)-sensitivity was also independent of the troponin I phosphorylation level (uncoupled). The recombinant K280N TnT mutation increased Ca(2+)-sensitivity 1.7-fold and was also uncoupled. The R92Q TnT mutation in troponin from transgenic mouse increased Ca(2+)-sensitivity and was also completely uncoupled. Five TnT mutations (Δ14, Δ28 + 7, ΔE160, S179F and K273E) studied in recombinant troponin increased Ca(2+)-sensitivity and were all fully uncoupled. Thus, for HCM-causing mutations in TnT, Ca(2+)-sensitisation together with uncoupling in vitro is the usual response and both factors may contribute to the HCM phenotype. We also found that Epigallocatechin-3-gallate (EGCG) can restore coupling to all uncoupled HCM-causing TnT mutations. In fact the combination of Ca(2+)-desensitisation and re-coupling due to EGCG completely reverses both the abnormalities found in troponin with a TnT HCM mutation suggesting it may have therapeutic potential.

  5. Long-term fertilization of a boreal Norway spruce forest increases the temperature sensitivity of soil organic carbon mineralization.

    Science.gov (United States)

    Coucheney, Elsa; Strömgren, Monika; Lerch, Thomas Z; Herrmann, Anke M

    2013-12-01

    Boreal ecosystems store one-third of global soil organic carbon (SOC) and are particularly sensitive to climate warming and higher nutrient inputs. Thus, a better description of how forest managements such as nutrient fertilization impact soil carbon (C) and its temperature sensitivity is needed to better predict feedbacks between C cycling and climate. The temperature sensitivity of in situ soil C respiration was investigated in a boreal forest, which has received long-term nutrient fertilization (22 years), and compared with the temperature sensitivity of C mineralization measured in the laboratory. We found that the fertilization treatment increased both the response of soil in situ CO2 effluxes to a warming treatment and the temperature sensitivity of C mineralization measured in the laboratory (Q10). These results suggested that soil C may be more sensitive to an increase in temperature in long-term fertilized in comparison with nutrient poor boreal ecosystems. Furthermore, the fertilization treatment modified the SOC content and the microbial community composition, but we found no direct relationship between either SOC or microbial changes and the temperature sensitivity of C mineralization. However, the relation between the soil C:N ratio and the fungal/bacterial ratio was changed in the combined warmed and fertilized treatment compared with the other treatments, which suggest that strong interaction mechanisms may occur between nutrient input and warming in boreal soils. Further research is needed to unravel into more details in how far soil organic matter and microbial community composition changes are responsible for the change in the temperature sensitivity of soil C under increasing mineral N inputs. Such research would help to take into account the effect of fertilization managements on soil C storage in C cycling numerical models.

  6. Increasing LIGO sensitivity by feedforward subtraction of auxiliary length control noise

    CERN Document Server

    Meadors, Grant David; Riles, Keith

    2013-01-01

    LIGO, the Laser Interferometer Gravitational-wave Observatory, has been designed and constructed to measure gravitational wave strain via differential arm length. The LIGO 4-km Michelson arms with Fabry-Perot cavities have auxiliary length control servos for suppressing Michelson motion of the beam-splitter and arm cavity input mirrors, which degrades interferometer sensitivity. We demonstrate how a post-facto pipeline called AMPS improves a data sample from LIGO Science Run~6 with feedforward subtraction. Dividing data into 1024-second windows, AMPS numerically fits filter functions representing the frequency-domain transfer functions from Michelson length channels into the gravitational-wave strain data channel for each window, then subtracts the filtered Michelson channel noise (witness) from the strain channel (target). In this paper we describe the algorithm, assess achievable improvements in sensitivity to astrophysical sources, and consider relevance to future interferometry.

  7. Lipopolysaccharide-Deficient Mutants of Salmonella enterica Have Increased Sensitivity to Catechins

    OpenAIRE

    Yoshii, Miho; OKAMOTO, Akira; Ota, Michio

    2013-01-01

    Antimicrobial activity is one of the well-known biological characteristics of catechins, the main extract of green tea leaves. It is thought that catechins intercalate into the bacterial cell membrane and damage the lipid bilayer. However, the association between catechins and lipopolysaccharides, which consist of an O side chain, core oligosaccharide, and lipid A, has not been previously investigated. In this study, we evaluated the catechin sensitivity of Salmonella enterica mutants that la...

  8. Increase in sensitivity of sensor units of environment refraction index change based on superficial plasmon resonance

    Directory of Open Access Journals (Sweden)

    Ushenin Yu. V.

    2011-04-01

    Full Text Available Results of computer modeling of an angular spectrum superficial plasmon resonance in metal films measurements with device PLAZMON-5 with infra-red radiator are analysed. It is shown that use of an infra-red source of radiation allows to improve sensitivity of sensor device in comparison with source of visible light. On an example of dielectric refraction indexes measurement with PLAZMON-5 device experimental check of theoretical calculations has been carried out.

  9. Very mild Alzheimer’s disease is characterized by increased sensitivity to mnemonic interference

    Science.gov (United States)

    Monti, Jim M.; Balota, David A.; Warren, David E.; Cohen, Neal J.

    2014-01-01

    Early pathology and tissue loss in Alzheimer’s disease (AD) occurs in the hippocampus, a brain region that has recently been implicated in relational processing irrespective of delay. Thus, tasks that involve relational processing will especially tax the hippocampal memory system, and should be sensitive to even mild dysfunction typical of early AD. Here we used a short-lag, short-delay memory task previously shown to be sensitive to hippocampal integrity in an effort to discriminate cognitive changes due to healthy aging from those associated with very mild AD. Young adults, healthy older adults, and individuals with very mild AD (N = 30 for each group) participated in our investigation, which entailed attempting to find an exact match to a previously presented target among a series of stimuli that varied in perceptual similarity to the target stimulus. Older adults with very mild AD were less accurate than healthy older adults, who, in turn, were impaired relative to young adults. Older adults with very mild AD were also particularly susceptible to interference from intervening lure stimuli. A measure based on this finding was able to explain additional variance in differentiating those in the very mild stage of AD from healthy older adults after accounting for episodic memory and global cognition composite scores in logistic regression models. Our findings suggest that cognitive changes in early stage AD reflect aging along with an additional factor potentially centered on sensitivity to interference, thereby supporting multifactorial models of aging. PMID:24747209

  10. Very mild Alzheimer׳s disease is characterized by increased sensitivity to mnemonic interference.

    Science.gov (United States)

    Monti, Jim M; Balota, David A; Warren, David E; Cohen, Neal J

    2014-07-01

    Early pathology and tissue loss in Alzheimer׳s disease (AD) occurs in the hippocampus, a brain region that has recently been implicated in relational processing irrespective of delay. Thus, tasks that involve relational processing will especially tax the hippocampal memory system, and should be sensitive to even mild dysfunction typical of early AD. Here we used a short-lag, short-delay memory task previously shown to be sensitive to hippocampal integrity in an effort to discriminate cognitive changes due to healthy aging from those associated with very mild AD. Young adults, healthy older adults, and individuals with very mild AD (N=30 for each group) participated in our investigation, which entailed attempting to find an exact match to a previously presented target among a series of stimuli that varied in perceptual similarity to the target stimulus. Older adults with very mild AD were less accurate than healthy older adults, who, in turn, were impaired relative to young adults. Older adults with very mild AD were also particularly susceptible to interference from intervening lure stimuli. A measure based on this finding was able to explain additional variance in differentiating those in the very mild stage of AD from healthy older adults after accounting for episodic memory and global cognition composite scores in logistic regression models. Our findings suggest that cognitive changes in early stage AD reflect aging along with an additional factor potentially centered on sensitivity to interference, thereby supporting multifactorial models of aging.

  11. Detection of shigella in lettuce by the use of a rapid molecular assay with increased sensitivity

    Directory of Open Access Journals (Sweden)

    Kenia Barrantes Jiménez

    2010-12-01

    Full Text Available A Multiplex Polymerase Chain Reaction (PCR assay to be used as an alternative to the conventional culture method in detecting Shigella and enteroinvasive Escherichia coli (EIEC virulence genes ipaH and ial in lettuce was developed. Efficacy and rapidity of the molecular method were determined as compared to the conventional culture. Lettuce samples were inoculated with different Shigella flexneri concentrations (from 10 CFU/ml to 10(7 CFU/ml. DNA was extracted directly from lettuce after inoculation (direct-PCR and after an enrichment step (enrichment PCR. Multiplex PCR detection limit was 10(4 CFU/ml, diagnostic sensitivity and specificity were 100% accurate. An internal amplification control (IAC of 100 bp was used in order to avoid false negative results. This method produced results in 1 to 2 days while the conventional culture method required 5 to 6 days. Also, the culture method detection limit was 10(6 CFU/ml, diagnostic sensitivity was 53% and diagnostic specificity was 100%. In this study a Multiplex PCR method for detection of virulence genes in Shigella and EIEC was shown to be effective in terms of diagnostic sensitivity, detection limit and amount of time as compared to Shigella conventional culture.

  12. Morphine sensitization increases the extracellular level of glutamate in CA1 of rat hippocampus via μ-opioid receptor.

    Science.gov (United States)

    Farahmandfar, Maryam; Karimian, Seyed Morteza; Zarrindast, Mohammad-Reza; Kadivar, Mehdi; Afrouzi, Hossein; Naghdi, Nasser

    2011-04-25

    Repeated administration of abuse drugs such as morphine elicits a progressive enhancement of drug-induced behavioral responses, a phenomenon termed behavioral sensitization. These changes in behavior may reflect plastic changes requiring regulation of glutamatergic system in the brain. In this study, we investigated the effect of morphine sensitization on extracellular glutamate concentration in the hippocampus, a brain region rich in glutamatergic neurons. Sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days free of the opioid treatment. The results showed that extracellular glutamate concentration in the CA1 was decreased following administration of morphine in non-sensitized rats. However, morphine-induced behavioral sensitization significantly increased the extracellular glutamate concentration in this area. The enhancement of glutamate in morphine sensitized rats was prevented by administration of naloxone 30 min before each of three daily doses of morphine. These results suggest an adaptation of the glutamatergic neuronal transmission in the hippocampus after morphine sensitization and it is postulated that opioid receptors may play an important role in this effect.

  13. Mothers' depressive symptoms predict both increased and reduced negative reactivity: aversion sensitivity and the regulation of emotion.

    Science.gov (United States)

    Dix, Theodore; Moed, Anat; Anderson, Edward R

    2014-07-01

    This study examined whether, as mothers' depressive symptoms increase, their expressions of negative emotion to children increasingly reflect aversion sensitivity and motivation to minimize ongoing stress or discomfort. In multiple interactions over 2 years, negative affect expressed by 319 mothers and their children was observed across variations in mothers' depressive symptoms, the aversiveness of children's immediate behavior, and observed differences in children's general negative reactivity. As expected, depressive symptoms predicted reduced maternal negative reactivity when child behavior was low in aversiveness, particularly with children who were high in negative reactivity. Depressive symptoms predicted high negative reactivity and steep increases in negative reactivity as the aversiveness of child behavior increased, particularly when high and continued aversiveness from the child was expected (i.e., children were high in negative reactivity). The findings are consistent with the proposal that deficits in parenting competence as depressive symptoms increase reflect aversion sensitivity and motivation to avoid conflict and suppress children's aversive behavior.

  14. Dietary fat restriction increases fat taste sensitivity in people with obesity

    OpenAIRE

    Newman, Lisa P.; Bolhuis, Dieuwerke P.; Susan J. Torres; Keast, Russell S. J.

    2016-01-01

    Objective Individuals with obesity may be less sensitive to the taste of fat, and it is hypothesized that this is due to excess dietary fat intake. This study assessed the effect of a 6‐week low‐fat (LF) or portion control (PC) diet matched for weight loss on fat taste thresholds, fat perception, and preference in people with overweight/obesity. Methods Participants (n = 53) completed a randomized dietary intervention and consumed either a LF diet (25% fat) or PC diet (33% fat) for 6 weeks. F...

  15. Coplanar Electrode Layout Optimized for Increased Sensitivity for Electrical Impedance Spectroscopy

    DEFF Research Database (Denmark)

    Clausen, Casper Hyttel; Skands, Gustav Erik; Bertelsen, Christian Vinther;

    2015-01-01

    This work describes an improvement in the layout of coplanar electrodes for electrical impedance spectroscopy. We have developed, fabricated, and tested an improved electrode layout, which improves the sensitivity of an impedance flow cytometry chip. The improved chip was experimentally tested...... and compared to a chip with a conventional electrode layout. The improved chip was able to discriminate 0.5 mu m beads from 1 mu m as opposed to the conventional chip. Furthermore, finite element modeling was used to simulate the improvements in electrical field density and uniformity between the electrodes...... of the new electrode layout. Good agreement was observed between the model and the obtained experimental results....

  16. Polymorphism in NEDD4L is associated with increased salt sensitivity, reduced levels of P-renin and increased levels of Nt-proANP.

    Directory of Open Access Journals (Sweden)

    Jonas Dahlberg

    Full Text Available OBJECTIVE: Neuronal precursor cell expressed developmentally down-regulated 4-like (NEDD4L is a regulator of the amiloride-sensitive epithelial sodium channel (ENaC, thus a candidate gene for salt sensitivity. Carriers of an intact NEDD4L C2-domain, encoded by the NEDD4L rs4149601 (G/A GG genotype, together with the C-allele of the NEDD4L rs2288774 (C/T polymorphism have previously been shown to have increased blood pressure. Our aim was to test if genetic variation in NEDD4L is associated with increased salt sensitivity. METHODS: 39 normotensive subjects were studied. The difference in 24-hour systolic blood pressure after four weeks on 150 mmol/day NaCl intake and four weeks on 50 mmol/day NaCl was defined as salt sensitivity. The rs4149601 and rs2288774 polymorphisms were genotyped using PCR-based techniques. RESULTS: Carriers of the rs4149601 GG-genotype together with the rs2288774 CC-genotype had significantly higher salt sensitivity (median, IQR (18.0, 7.5-20.0 mmHg vs 6.0, 0.0-10.0 mmHg, P = 0.007 and lower plasma renin concentration (P-renin (6.0, 2.0-9.5 mU/L vs 15.0, 9.0-24.0 mU/L, P = 0.005 as compared to non-carriers of these genotypes. In carriers of the rs4149601 GG-genotype together with the rs2288774 CC- or CT-genotype, as compared to non-carriers, salt sensitivity was (8.0, 6.0-18.0 mmHg vs 5.0, 0.0-10.0 mmHg, P = 0.07 and P-renin (9.0, 6.0-16.0 mU/L vs 15.0, 9.0-28.0 mU/L, P = 0.03. CONCLUSION: Genetic NEDD4L variation seems to affect salt sensitivity and P-renin in normotensive subjects, suggesting that genotyping of NEDD4L may be clinically useful in order to identify subjects who benefit from dietary salt restriction in the prevention of hypertension.

  17. Increased effort requirements and risk sensitivity: a comparison of delay and magnitude manipulations.

    Science.gov (United States)

    Kirshenbaum, Ari P.; Szalda-Petree, Allen D.; Haddad, Nabil F.

    2003-03-31

    Reward magnitude and delay to reward were independently manipulated in two separate experiments examining risk-sensitive choice in rats. A dual-running wheel apparatus was used and the tangential force resistance required to displace both wheels was low (50g) for half of the subjects, and high (120g) for the remaining subjects. Concurrent FI30-s and FI60-s schedules delivered equivalent amounts of food reward per unit time (i.e. 5 and 10 pellets of food, respectively), and these conditions served as the baseline treatment for all subjects. Variability, either in reward magnitude or delay, was introduced on the long-delay (60s) schedule during the second phase. All subjects were returned to the baseline condition in the third phase, and variability was introduced on the short-delay (30s) interval schedule during phase four. The subjects were again returned to the baseline condition in the fifth and final phase, ultimately yielding a five-phase ABACA design. Original baseline performance was characterized by a slight short-delay interval preference, and this pattern of performance was recovered with each subsequent presentation of the baseline condition. Overall, the data obtained from the reward magnitude and delay-to-reward manipulations were indistinguishable; subjects experiencing low-response effort requirement behaved in a risk-indifferent manner and subjects experiencing high-response effort requirement preferred the variable schedule. Implications for the daily energy budget rule on risk-sensitive foraging are discussed in light of these findings.

  18. Increasing LIGO sensitivity by feedforward subtraction of auxiliary length control noise

    Science.gov (United States)

    Meadors, Grant; Kawabe, Keita; Riles, Keith

    2013-04-01

    LIGO, the Laser Interferometer Gravitational-wave Observatory [Hanford, Washington and Livingston, Louisiana] measures the differential length of 4-km Michelson arms with Fabry-Perot cavities. Length changes could indicate strain caused by astrophysical sources of gravitational waves. Fundamentally limited by seismic noise, thermal suspension noise, and laser shot noise in different frequency bands, a LIGO interferometer's sensitivity can also be degraded by additional relative motion of the inner arm cavity mirrors due to imperfectly-servoed Michelson motion. In this project we seek to subtract the effects of this residual motion by feedforward correction of the gravitational-wave data channel. We divide data from LIGO's sixth science run into 1024-second time windows and numerically fit a filter representing the frequency-domain transfer function from Michelson servo noise to gravitational wave channel for each window. Finally, the Michelson servo channel is processed through the filter and is subtracted from the gravitational-wave signal channel. The algorithm used in this procedure will be described with a preliminary assessment of the achievable sensitivity improvement.

  19. Renaturation of blotted allergens increases the sensitivity of specific IgE detection.

    Science.gov (United States)

    Muro, M D; Fernández, C; Moneo, I

    1996-01-01

    Several authors have demonstrated that renaturation is an essential step for the appropriate recognition of blotted proteins. The use of nonionic detergents has been described as a useful alternative to enhance the antigenicity in immunoblotting, although elution from proteins by detergents has been observed. To measure the influence of different factors on the sensitivity of specific IgE by immunoblotting, we used twenty human sera from atopic patients who were allergic or nonallergic to a common, reliable allergen (grass pollen mixture). The use of Nonidet-P40 was found to be a useful alternative for the renaturation of the allergens. No elution from the membrane was found when employing this detergent, even at high concentrations (3%), and its use gave better sensitivity than methanol. On the other hand, we detected that methanol possessed renaturing properties. A transfer method using diffusion instead of electric transfer gave the best results and two membranes could be obtained from each gel. Using this method, we found that after NP-40 incubation of the membrane, the use of bovine albumin could be omitted as blocking agent and that its use had even deleterious effects.

  20. Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms.

    Science.gov (United States)

    Kang, Changkeun; Lee, Hyunkyoung; Jung, Eun-Sun; Seyedian, Ramin; Jo, MiNa; Kim, Jehein; Kim, Jong-Shu; Kim, Euikyung

    2012-12-15

    Saffron (Crocus sativus Linn.) has been an important subject of research in the past two decades because of its various biological properties, including anti-cancer, anti-inflammatory, and anti-atherosclerotic activities. On the other hand, the molecular bases of its actions have been scarcely understood. Here, we elucidated the mechanism of the hypoglycemic actions of saffron through investigating its signaling pathways associated with glucose metabolism in C(2)C(12) skeletal muscle cells. Saffron strongly enhanced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase) and MAPKs (mitogen-activated protein kinases), but not PI 3-kinase (Phosphatidylinositol 3-kinase)/Akt. Interestingly, the co-treatment of saffron and insulin further improved the insulin sensitivity via both insulin-independent (AMPK/ACC and MAPKs) and insulin-dependent (PI 3-kinase/Akt and mTOR) pathways. It also suggested that there is a crosstalk between the two signaling pathways of glucose metabolism in skeletal muscle cells. These results could be confirmed from the findings of GLUT4 translocation. Taken together, AMPK plays a major role in the effects of saffron on glucose uptake and insulin sensitivity in skeletal muscle cells. Our study provides important insights for the possible mechanism of action of saffron and its potential as a therapeutic agent in diabetic patients.

  1. Increased sensitivity of an adriamycin-resistant human small cell lung carcinoma cell line to mitochondrial inhibitors

    NARCIS (Netherlands)

    de Jong, Steven; Holtrop, M; de Vries, H; de Vries, Liesbeth; Mulder, N H

    1992-01-01

    The energy metabolism of an atypical multidrug resistant human small cell lung carcinoma cell line (GLC4/ADR) was studied. The glycolytic rate was 30% reduced and the glucose-6-phosphate dehydrogenase activity 2-fold increased in GLC4/ADR compared to the parental sensitive line (GLC4). Although mito

  2. Has the sensitivity of soybean cultivars to ozone pollution increased with time? An analysis of published dose-response data

    Science.gov (United States)

    The rising trend in concentrations of ground-level ozone (O3) – a common air pollutant and phytotoxin – currently being experienced in some world regions represents a threat to agricultural yield. Soybean (Glycine max (L.) Merr.) is an O3-sensitive crop species, and is experiencing increasing globa...

  3. Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice : spinal cord c-Fos expression and behavior

    NARCIS (Netherlands)

    Eijkelkamp, Niels; Kavelaars, Annemieke; Elsenbruch, Sigrid; Schedlowski, Manfred; Holtmann, Gerald; Heijnen, Cobi J.

    2007-01-01

    Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice: spinal cord c-Fos expression and behavior. Am J Physiol Gastrointest Liver Physiol 293: G749-G757, 2007. First published July 26, 2007; doi:10.1152/ajpgi.00114.2007.During acute and chronic inflammation visceral pain perc

  4. Delta(9)-tetrahydrocannabinol activates [Ca2+], increases partly sensitive to capacitative store refilling

    NARCIS (Netherlands)

    Filipeanu, CM; deZeeuw, D; Nelemans, SA

    1997-01-01

    Delta(9)-Tetrahydrocannabinol induces [Ca2+](i) increases in DDT1MF-2 smooth muscle cells. Both Ca2+ entry and release from intracellular Ca2+ stores were concentration dependently activated. The Ca2+ entry component contributed most to the increases in [Ca2+](i). Stimulation with Delta(9)-tetrahydr

  5. 3D numerical simulation of a lab-on-a-chip--increasing measurement sensitivity of interdigitated capacitors by passivation optimization.

    Science.gov (United States)

    Jungreuthmayer, Christian; Birnbaumer, Gerald M; Zanghellini, Juergen; Ertl, Peter

    2011-04-07

    Interdigital electrode structures (IDES) play a major role in many technical and analytical applications. In particular, they are a key technology in modern lab-on-a-chip (LOC) devices. As high sensitivity is a key component of any (bio)analytical method, the presented work is aimed at designing a novel dielectric sensing system, which exhibits maximum sensor sensitivity using passivated dielectric microsensors. Although the implementation of high-ε(r) dielectric passivation materials such as tantalum oxide or titanium oxide showed increased sensor sensitivity by a factor of 5, simulations revealed that sensor sensitivity is ultimately determined by the dielectric properties of the analyte. Ideally, dielectric properties of the passivation material need to be adjusted to the dielectric properties of the material under investigation and any deviations (e.g. higher or lower dielectric constants) will result in significant loss of sensitivity. To address these shortcomings we have developed a novel dielectric sensing concept based on a dual-material passivation geometry. The novel design consists of electric flux barriers that are layered between the finger electrodes, as well as electric flux guides which are located above the electrode structures that direct the entire generated electric flux to the object under investigation. Our 3D numerical results clearly show that the novel design offers two main advantages: firstly, the measurement sensitivity is further increased by more than a factor of two in comparison to a homogeneous passivation material sensing strategy. Secondly, maximum sensitivity for a given set of finger geometries can be achieved using a single sensor design regardless of the frequency-dependent dielectric properties of the measured objects. Hence, the novel approach is capable of reducing design and manufacturing costs of lab-on-a-chip devices.

  6. Increased Prepulse Inhibition and Sensitization of the Startle Reflex in Autistic Children

    DEFF Research Database (Denmark)

    Madsen, Gitte Falcher; Bilenberg, Niels; Cantio, Cathriona;

    2014-01-01

    The relation between autism spectrum disorders (ASD) and schizophrenia is a subject of intense debate and research due to evidence of common neurobiological pathways in the two disorders. The objective of this study was to explore whether deficits in prepulse inhibition (PPI) of the startle reflex...... and 40 matched NTD controls were tested in a psychophysiological test battery. The PPI of the acoustic startle reflex was analyzed in 18 ASD subjects and 34 NTD controls. Habituation and sensitization were analyzed in 23 ASD subjects and 39 NTD controls. In trials with less intense prestimuli (76 d....... The relation to PPI deficits observed in schizophrenia is not apparent. Future research should study the developmental course of PPI deficits in ASD patients in a longitudinal design. Autism Res 2013, ●●: ●●-●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc....

  7. Increasing the sensitivity for stem cell monitoring in system-function based magnetic particle imaging

    Science.gov (United States)

    Them, Kolja; Salamon, J.; Szwargulski, P.; Sequeira, S.; Kaul, M. G.; Lange, C.; Ittrich, H.; Knopp, Tobias

    2016-05-01

    The use of superparamagnetic iron oxide nanoparticles (SPIONs) has provided new possibilities in biophysics and biomedical imaging technologies. The magnetization dynamics of SPIONs, which can be influenced by the environment, are of central interest. In this work, different biological SPION environments are used to investigate three different calibration methods for stem cell monitoring in magnetic particle imaging. It is shown that calibrating using SPIONs immobilized via agarose gel or intracellular uptake results in superior stem cell image quality compared to mobile SPIONs in saline. This superior image quality enables more sensitive localization and identification of a significantly smaller number of magnetically labeled stem cells. The results are important for cell tracking and monitoring of future SPION based therapies such as hyperthermia based cancer therapies, targeted drug delivery, or tissue regeneration approaches where it is crucial to image a sufficiently small number of SPIONs interacting with biological matter.

  8. Increasing the sensitivity of future gravitational-wave detectors with double squeezed-input

    CERN Document Server

    Khalili, Farid Ya; Chen, Yanbei

    2009-01-01

    We consider improving the sensitivity of future interferometric gravitational-wave detectors by simultaneously injecting two squeezed vacuums (light), filtered through a resonant Fabry-Perot cavity, into the dark port of the interferometer.The same scheme with single squeezed vacuum was first proposed and analyzed by Corbitt et al. Here we show that the extra squeezed vacuum, together with an additional homodyne detection suggested previously by one of the authors, allows reduction of quantum noise over the entire detection band. To motivate future implementations, we take into account a realistic technical noise budget for Advanced LIGO (AdvLIGO) and numerically optimize the parameters of both the filter and the interferometer for detecting gravitational-wave signals from two important astrophysics sources, namely Neutron-Star--Neutron-Star (NSNS) binaries and Bursts. Assuming the optical loss of the 30m filter cavity to be 10ppm per bounce and 10dB squeezing injection, the corresponding quantum noise with o...

  9. Mars-GRAM: Increasing the Precision of Sensitivity Studies at Large Optical Depths

    Science.gov (United States)

    Justh, Hilary L.; Justus, C. G.; Badger, Andrew M.

    2010-01-01

    The Mars Global Reference Atmospheric Model (Mars-GRAM) is an engineering-level atmospheric model widely used for diverse mission applications. Mars-GRAM's perturbation modeling capability is commonly used, in a Monte-Carlo mode, to perform high fidelity engineering end-to-end simulations for entry, descent, and landing (EDL). It has been discovered during the Mars Science Laboratory (MSL) site selection process that Mars-GRAM, when used for sensitivity studies for MapYear=0 and large optical depth values such as tau=3, is less than realistic. A comparison study between Mars atmospheric density estimates from Mars-GRAM and measurements by Mars Global Surveyor (MGS) has been undertaken for locations of varying latitudes, Ls, and LTST on Mars. The preliminary results from this study have validated the Thermal Emission Spectrometer (TES) limb data. From the surface to 80 km altitude, Mars-GRAM is based on the NASA Ames Mars General Circulation Model (MGCM). MGCM results that were used for Mars-GRAM with MapYear=0 were from a MGCM run with a fixed value of tau=3 for the entire year at all locations. This has resulted in an imprecise atmospheric density at all altitudes. To solve this pressure-density problem, density factor values were determined for tau=.3, 1 and 3 that will adjust the input values of MGCM MapYear 0 pressure and density to achieve a better match of Mars-GRAM MapYear 0 with TES observations for MapYears 1 and 2 at comparable dust loading. The addition of these density factors to Mars-GRAM will improve the results of the sensitivity studies done for large optical depths.

  10. Exercise-induced increase in IL-6 level enhances GLUT4 expression and insulin sensitivity in mouse skeletal muscle.

    Science.gov (United States)

    Ikeda, Shin-Ichi; Tamura, Yoshifumi; Kakehi, Saori; Sanada, Hiromi; Kawamori, Ryuzo; Watada, Hirotaka

    2016-05-13

    A single bout of exercise is known to increase the insulin sensitivity of skeletal muscle; however, the underlying mechanism of this phenomenon is not fully understood. Because a single bout of exercise induces a transient increase in blood interleukin-6 (IL-6) level, we hypothesized that the enhancement of insulin sensitivity after a single bout of exercise in skeletal muscle is mediated at least in part through IL-6-dependent mechanisms. To test this hypothesis, C57BL6J mice were intravenously injected with normal IgG or an IL-6 neutralizing antibody before exercise. Twenty-four hours after a single bout of exercise, the plantaris muscle was harvested to measure insulin sensitivity and glucose transporter (GLUT)-4 expression levels by ex-vivo insulin-stimulated 2-deoxyglucose (2-DG) uptake and Western blotting, respectively. Compared with sedentary mice, mice that performed exercise showed enhanced IL-6 concentration, insulin-stimulated 2-DG uptake, and GLUT-4 expression in the plantaris muscle. The enhanced insulin sensitivity and GLUT4 expression were canceled by injection of the IL-6 neutralizing antibody before exercise. In addition, IL-6 injection increased GLUT4 expression, both in the plantaris muscle and the soleus muscle in C57BL6J mice. Furthermore, a short period of incubation with IL-6 increased GLUT4 expression in differentiated C2C12 myotubes. In summary, these results suggested that IL-6 increased GLUT4 expression in muscle and that this phenomenon may play a role in the post-exercise enhancement of insulin sensitivity in skeletal muscle.

  11. Increased glucocorticoid sensitivity in pancreatic beta-cells : Effects on glucose metabolism and insulin release

    OpenAIRE

    Davani, Behrous

    2003-01-01

    Type 2 diabetes mellitus (T2DM) is characterized by three pathological alterations: (1) insulin resistance in peripheral tissues, (2) increased hepatic glucose production and (3) impaired insulin secretion from the pancreatic beta-cells. Glucocorticoids (GCs) exert profound effects on glucose homeostasis. They decrease glucose uptake and increase hepatic glucose production. In addition, they may directly inhibit insulin release. The main aim of this thesis was to investigate...

  12. Sensitivity of a prairie wetland to increased temperature and seasonal precipitation changes

    Energy Technology Data Exchange (ETDEWEB)

    Poiani, K.A. [Cornell Univ., Ithaca, NY (United States); Johnson, W.C. [South Dakota State Univ., Brookings, SD (United States); Kittel, T.G.F. [Univ. Corp. for Atmospheric Research, Boulder, CO (United States)]|[Colorado State Univ., Fort Collins, CO (United States)

    1995-04-01

    We assessed the potential effects of increased temperature and changes in amount and seasonal timing of precipitation on the hydrology and vegetation of a semi-permanent prairie wetland in North Dakota using a spatially-defined, rule-based simulation model. Simulations were run with increased temperatures of 2{degree}C combined with a 10 percent increase or decrease in total growing season precipitation. Changes in precipitation were applied either evenly across all months or to individual seasons (spring, summer, or fall). The response of semi-permanent wetland P1 was relatively similar under most of the seasonal scenarios. A 10 percent increase in total growing season precipitation applied to summer months only, to fall months only, and over all months produced lower water levels compared to those resulting from the current climate due to increased evapotranspiration. Wetland hydrology was most affected by changes in spring precipitation and runoff. Vegetation response was relatively consistent across scenarios. Seven of the eight seasonal scenarios produced drier conditions with no open water and greater vegetation cover compared to those resulting from the current climate. Only when spring precipitation increased did the wetland maintain an extensive open water area (49 percent). 36 refs., 3 figs., 3 tabs.

  13. Improving Mars-GRAM: Increasing the Accuracy of Sensitivity Studies at Large Optical Depths

    Science.gov (United States)

    Justh, Hilary L.; Justus, C. G.; Badger, Andrew M.

    2010-01-01

    Extensively utilized for numerous mission applications, the Mars Global Reference Atmospheric Model (Mars-GRAM) is an engineering-level atmospheric model. In a Monte-Carlo mode, Mars-GRAM's perturbation modeling capability is used to perform high fidelity engineering end-to-end simulations for entry, descent, and landing (EDL). Mars-GRAM has been found to be inexact when used during the Mars Science Laboratory (MSL) site selection process for sensitivity studies for MapYear=0 and large optical depth values such as tau=3. Mars-GRAM is based on the NASA Ames Mars General Circulation Model (MGCM) from the surface to 80 km altitude. Mars-GRAM with the MapYear parameter set to 0 utilizes results from a MGCM run with a fixed value of tau=3 at all locations for the entire year. Imprecise atmospheric density and pressure at all altitudes is a consequence of this use of MGCM with tau=3. Density factor values have been determined for tau=0.3, 1 and 3 as a preliminary fix to this pressure-density problem. These factors adjust the input values of MGCM MapYear 0 pressure and density to achieve a better match of Mars-GRAM MapYear 0 with Thermal Emission Spectrometer (TES) observations for MapYears 1 and 2 at comparable dust loading. These density factors are fixed values for all latitudes and Ls and are included in Mars-GRAM Release 1.3. Work currently being done, to derive better multipliers by including variations with latitude and/or Ls by comparison of MapYear 0 output directly against TES limb data, will be highlighted in the presentation. The TES limb data utilized in this process has been validated by a comparison study between Mars atmospheric density estimates from Mars-GRAM and measurements by Mars Global Surveyor (MGS). This comparison study was undertaken for locations on Mars of varying latitudes, Ls, and LTST. The more precise density factors will be included in Mars-GRAM 2005 Release 1.4 and thus improve the results of future sensitivity studies done for large

  14. Incubating rainbow trout in soft water increased their later sensitivity to cadmium and zinc

    Science.gov (United States)

    Mebane, Christopher A.; Hennessy, Daniel P.; Dillon, Frank S.

    2010-01-01

    Water hardness is well known to affect the toxicity of some metals; however, reports on the influence of hardness during incubation or acclimation on later toxicity to metals have been conflicting. We incubated rainbow trout (Oncorhynchus mykiss) near the confluence of two streams, one with soft water and one with very-soft water (average incubation hardnesses of about 21 and 11 mg/L as CaCO3, respectively). After developing to the swim-up stage, the fish were exposed for 96-h to a mixture of cadmium (Cd) and zinc (Zn) in water with a hardness of 27 mg/L as CaCO3. The fish incubated in the higher hardness water were about two times more resistant than the fish incubated in the extremely soft water. This difference was similar or greater than the difference that would have been predicted by criteria hardness equations had the fish been tested in the different acclimation waters. We think it is plausible that the energy demands for fish to maintain homeostasis in the lower hardness water make the fish more sensitive to metals that inhibit ionoregulation such as Cd and Zn. We suggest that if important decisions were to be based upon test results, assumptions of adequate hardness acclimation should be carefully considered and short acclimation periods avoided. If practical, incubating rainbow trout in the control waters to be tested may reduce uncertainties in the possible influences of differing rearing water hardness on the test results.

  15. Coral population trajectories, increased disturbance and management intervention: a sensitivity analysis.

    Science.gov (United States)

    Riegl, Bernhard; Berumen, Michael; Bruckner, Andrew

    2013-04-01

    Coral reefs distant from human population were sampled in the Red Sea and one-third showed degradation by predator outbreaks (crown-of-thorns-starfish = COTS observed in all regions in all years) or bleaching (1998, 2010). Models were built to assess future trajectories. They assumed variable coral types (slow/fast growing), disturbance frequencies (5,10,20 years), mortality (equal or not), and connectivity (un/connected to un/disturbed community). Known disturbances were used to parameterize models. Present and future disturbances were estimated from remote-sensing chlorophyll and temperature data. Simulations and sensitivity analysis suggest community resilience at >20-year disturbance frequency, but degradation at higher frequency. Trajectories move from fast-grower to slow-grower dominance at intermediate disturbance frequency, then again to fast-grower dominance. A similar succession was observed in the field: Acropora to Porites to Stylophora/Pocillopora dominance on shallow reefs, and a transition from large poritids to small faviids on deep reefs. Synthesis and application: Even distant reefs are impacted by global changes. COTS impacts and bleaching were key driver of coral degradation, coral population decline could be reduced if these outbreaks and bleaching susceptibility were managed by maintaining water quality and by other interventions. Just leaving reefs alone, seems no longer a satisfactory option.

  16. Coral population trajectories, increased disturbance and management intervention: A sensitivity analysis

    KAUST Repository

    Riegl, Bernhard

    2013-03-07

    Coral reefs distant from human population were sampled in the Red Sea and one-third showed degradation by predator outbreaks (crown-of-thorns-starfish=COTS observed in all regions in all years) or bleaching (1998, 2010). Models were built to assess future trajectories. They assumed variable coral types (slow/fast growing), disturbance frequencies (5,10,20years), mortality (equal or not), and connectivity (un/connected to un/disturbed community). Known disturbances were used to parameterize models. Present and future disturbances were estimated from remote-sensing chlorophyll and temperature data. Simulations and sensitivity analysis suggest community resilience at >20-year disturbance frequency, but degradation at higher frequency. Trajectories move from fast-grower to slow-grower dominance at intermediate disturbance frequency, then again to fast-grower dominance. A similar succession was observed in the field: Acropora to Porites to Stylophora/Pocillopora dominance on shallow reefs, and a transition from large poritids to small faviids on deep reefs. Synthesis and application: Even distant reefs are impacted by global changes. COTS impacts and bleaching were key driver of coral degradation, coral population decline could be reduced if these outbreaks and bleaching susceptibility were managed by maintaining water quality and by other interventions. Just leaving reefs alone, seems no longer a satisfactory option. 2013 The Authors. Ecology and Evolution.

  17. MEK5/ERK5 signaling inhibition increases colon cancer cell sensitivity to 5-fluorouracil through a p53-dependent mechanism

    Science.gov (United States)

    Pereira, Diane M.; Simões, André E. S.; Gomes, Sofia E.; Castro, Rui E.; Carvalho, Tânia; Rodrigues, Cecília M. P.; Borralho, Pedro M.

    2016-01-01

    The MEK5/ERK5 signaling pathway is emerging as an important contributor to colon cancer onset, progression and metastasis; however, its relevance to chemotherapy resistance remains unknown. Here, we evaluated the impact of the MEK5/ERK5 cascade in colon cancer cell sensitivity to 5-fluorouracil (5-FU). Increased ERK5 expression was correlated with poor overall survival in colon cancer patients. In colon cancer cells, 5-FU exposure impaired endogenous KRAS/MEK5/ERK5 expression and/or activation. In turn, MEK5 constitutive activation reduced 5-FU-induced cytotoxicity. Using genetic and pharmacological approaches, we showed that ERK5 inhibition increased caspase-3/7 activity and apoptosis following 5-FU exposure. Mechanistically, this was further associated with increased p53 transcriptional activation of p21 and PUMA. In addition, ERK5 inhibition increased the response of HCT116 p53+/+ cells to 5-FU, but failed to sensitize HCT116 p53−/− cells to the cytotoxic effects of this chemotherapeutic agent, suggesting a p53-dependent axis mediating 5-FU sensitization. Finally, ERK5 inhibition using XMD8-92 was shown to increase the antitumor effects of 5-FU in a murine subcutaneous xenograft model, enhancing apoptosis while markedly reducing tumor growth. Collectively, our results suggest that ERK5-targeted in hibition provides a promising therapeutic approach to overcome resistance to 5-FU-based chemotherapy and improve colon cancer treatment. PMID:27144434

  18. Image stacking approach to increase sensitivity of fluorescence detection using a low cost complementary metal-oxide-semiconductor (CMOS) webcam.

    Science.gov (United States)

    Balsam, Joshua; Bruck, Hugh Alan; Kostov, Yordan; Rasooly, Avraham

    2012-01-01

    Optical technologies are important for biological analysis. Current biomedical optical analyses rely on high-cost, high-sensitivity optical detectors such as photomultipliers, avalanched photodiodes or cooled CCD cameras. In contrast, Webcams, mobile phones and other popular consumer electronics use lower-sensitivity, lower-cost optical components such as photodiodes or CMOS sensors. In order for consumer electronics devices, such as webcams, to be useful for biomedical analysis, they must have increased sensitivity. We combined two strategies to increase the sensitivity of CMOS-based fluorescence detector. We captured hundreds of low sensitivity images using a Webcam in video mode, instead of a single image typically used in cooled CCD devices.We then used a computational approach consisting of an image stacking algorithm to remove the noise by combining all of the images into a single image. While video mode is widely used for dynamic scene imaging (e.g. movies or time-lapse photography), it is not used to capture a single static image, which removes noise and increases sensitivity by more than thirty fold. The portable, battery-operated Webcam-based fluorometer system developed here consists of five modules: (1) a low cost CMOS Webcam to monitor light emission, (2) a plate to perform assays, (3) filters and multi-wavelength LED illuminator for fluorophore excitation, (4) a portable computer to acquire and analyze images, and (5) image stacking software for image enhancement. The samples consisted of various concentrations of fluorescein, ranging from 30 μM to 1000 μM, in a 36-well miniature plate. In the single frame mode, the fluorometer's limit-of-detection (LOD) for fluorescein is ∼1000 μM, which is relatively insensitive. However, when used in video mode combined with image stacking enhancement, the LOD is dramatically reduced to 30 μM, sensitivity which is similar to that of state-of-the-art ELISA plate photomultiplier-based readers. Numerous medical

  19. Increased sensitivity of anodic stripping voltammetry at the hanging mercury drop electrode by ultracathodic deposition

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Jose A.; Rodrigues, Carlos M.; Almeida, Paulo J.; Valente, Ines M.; Goncalves, Luis M. [Requimte - Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade do Porto, Rua do Campo Alegre, no. 687, 4169-007 Porto (Portugal); Compton, Richard G. [Department of Chemistry, Physical and Theoretical Chemistry Laboratory, Oxford University, South Parks Road, Oxford OX1 3QZ (United Kingdom); Barros, Aquiles A., E-mail: ajbarros@fc.up.pt [Requimte - Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade do Porto, Rua do Campo Alegre, no. 687, 4169-007 Porto (Portugal)

    2011-09-09

    Highlights: {yields} At very cathodic accumulation potentials (overpotential deposition) the voltammetric signals of Zn{sup 2+}, Cd{sup 2+}, Pb{sup 2+} and Cu{sup 2+} increase. {yields} 5 to 10-fold signal increase is obtained. {yields} This effect is likely due to mercury drop oscillation at such cathodic potentials. {yields} This effect is also likely due to added local convection at the mercury drop surface caused by the evolution of hydrogen bubbles. - Abstract: An improved approach to the anodic stripping voltammetric (ASV) determination of heavy metals, using the hanging mercury drop electrode (HMDE), is reported. It was discovered that using very cathodic accumulation potentials, at which the solvent reduction occurs (overpotential deposition), the voltammetric signals of zinc(II), cadmium(II), lead(II) and copper(II) increase. When compared with the classical methodology a 5 to 10-fold signal increase is obtained. This effect is likely due to both mercury drop oscillation at such cathodic potentials and added local convection at the mercury drop surface caused by the evolution of hydrogen bubbles.

  20. Targeted disruption of the CREB coactivator Crtc2 increases insulin sensitivity

    DEFF Research Database (Denmark)

    Wang, Yiguo; Inoue, Hiroshi; Ravnskjær, Kim

    2010-01-01

    Under fasting conditions, increases in circulating concentrations of pancreatic glucagon maintain glucose homeostasis through induction of gluconeogenic genes by the CREB coactivator CRTC2. Hepatic CRTC2 activity is elevated in obesity, although the extent to which this cofactor contributes to at...

  1. Competition increases sensitivity of wheat (Triticum aestivum) to biotic plant-soil feedback

    NARCIS (Netherlands)

    Hol, W.H.G.; Boer, de W.; Hooven, ten F.; Putten, van der W.H.

    2013-01-01

    Plant-soil feedback (PSF) and plant competition play an important role in structuring vegetation composition, but their interaction remains unclear. Recent studies suggest that competing plants could dilute pathogenic effects, whereas the standing view is that competition may increase the sensitivit

  2. Mental stress-induced increase in blood pressure is not related to baroreflex sensitivity in middle-aged healthy men.

    Science.gov (United States)

    Fauvel, J P; Cerutti, C; Quelin, P; Laville, M; Gustin, M P; Paultre, C Z; Ducher, M

    2000-04-01

    The baroreflex that acts to blunt blood pressure (BP) variations through opposite variations in heart rate should limit the BP increase produced by an emotional challenge. However, relations between baroreflex sensitivity and BP reactivity induced by a psychological stress in a large group of adults have never been firmly established. In 280 healthy men, rest (10 minutes) and stress (5 minutes) BP and heart rate were recorded beat to beat by a blood pressure monitor. The mental stress was elicited by a well-standardized computerized version of a word color conflict stress test (Stroop Color Test). Rest and stress baroreflex sensitivity was assessed by the cross-spectral analysis of BP and heart rate and by the sequence method. The stress-induced increase in systolic BP (22.4+/-0.1 mm Hg) was not correlated with resting baroreflex sensitivity but was slightly correlated (r=0.2, P<0.001) with BP variability assessed either by standard deviation or by mid-frequency band spectral power. Our results suggested that a centrally mediated sympathetic stimulation overcame cardiac autonomic regulation and emphasized the role of the sympathetic vasoconstriction in the pressure response at the onset of the stressing stimulation. During the sustained sympathoexcitatory phase, the cardiac baroreflex blunts BP variations but at a lower sensitivity.

  3. Cell cycle-arrested tumor cells exhibit increased sensitivity towards TRAIL-induced apoptosis

    Science.gov (United States)

    Ehrhardt, H; Wachter, F; Grunert, M; Jeremias, I

    2013-01-01

    Resting tumor cells represent a huge challenge during anticancer therapy due to their increased treatment resistance. TNF-related apoptosis-inducing ligand (TRAIL) is a putative future anticancer drug, currently in phases I and II clinical studies. We recently showed that TRAIL is able to target leukemia stem cell surrogates. Here, we tested the ability of TRAIL to target cell cycle-arrested tumor cells. Cell cycle arrest was induced in tumor cell lines and xenografted tumor cells in G0, G1 or G2 using cytotoxic drugs, phase-specific inhibitors or RNA interference against cyclinB and E. Biochemical or molecular arrest at any point of the cell cycle increased TRAIL-induced apoptosis. Accordingly, when cell cycle arrest was disabled by addition of caffeine, the antitumor activity of TRAIL was reduced. Most important for clinical translation, tumor cells from three children with B precursor or T cell acute lymphoblastic leukemia showed increased TRAIL-induced apoptosis upon knockdown of either cyclinB or cyclinE, arresting the cell cycle in G2 or G1, respectively. Taken together and in contrast to most conventional cytotoxic drugs, TRAIL exerts enhanced antitumor activity against cell cycle-arrested tumor cells. Therefore, TRAIL might represent an interesting drug to treat static-tumor disease, for example, during minimal residual disease. PMID:23744361

  4. Cadmium Increases the Sensitivity of Adolescent Female Mice to Nicotine-Related Behavioral Deficits

    Directory of Open Access Journals (Sweden)

    Philip Adeyemi Adeniyi

    2014-01-01

    Full Text Available This study investigates spatial and nonspatial working memory, anxiety related behavior, and motor activities in cadmium and/or nicotine exposed female adolescent mice. P28 female adolescent mice (albino strain were divided into four groups of five (n=5 mice each. A set of mice (Nic received subcutaneous nicotine (2.0 mg/kg while a separate set (Cd was treated with 2.0 mg/kg cadmium (subcutaneous. For the combined treatments of cadmium and nicotine, we administered 2.0 mg/kg Nicotine and 2.0 mg/kg of Cd. Subsequently, a separate group of animals (n=5; control received normal saline. The total duration of treatment for all groups was 28 days (P28–P56. At P56, the treatment was discontinued, after which the animals were examined in behavioural tests. Nicotine and cadmium increased the metabolism and food intake in the female adolescent mice. This also corresponded to an increase in weight when compared with the control. However, a combined nicotine-cadmium treatment induced a decline in weight of the animals versus the control. Also, nicotine administration increased the motor function, while cadmium and nicotine-cadmium treatment caused a decline in motor activity. Both nicotine and cadmium induced a reduction in memory index; however, nicotine-cadmium treatment induced the most significant decrease in nonspatial working memory.

  5. Overexpression of SOS (Salt Overly Sensitive)Genes Increases Salt Tolerance in Transgenic Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Qing Yang; Zhi-Zhong Chen; Xiao-Feng Zhoua; Hai-Bo Yin; Xia Li; Xiu-Fang Xin; Xu-Hui Hong; Jian-Kang Zhu; Zhizhong Gong

    2009-01-01

    Soil salinity is a major abiotic stress that decreases plant growth and productivity. Recently, it was reported that plants overexpressing AtNHX1 or SOS1 have significantly increased salt tolerance. To test whether overexpression of multiple genes can improve plant salt tolerance even more, we produced six different transgenic Arabidopsis plants that overexpress AtNHX1, SOS3, AtNHXl + SOS3, SOS1, SOS2 + SOS3, or SOS1 + SOS2 + SOS3. Northern blot analyses confirmed the presence of high levels of the relevant gene transcripts in transgenic plants. Transgenic Arabidopsis plants overexpressing AtNHX1 alone did not present any significant increase in salt tolerance, contrary to earlier reports. We found that transgenic plants overexpressing SOS3 exhibit increased salt tolerance similar to plants overexpressing SOS1. Moreover, salt tolerance of transgenic plants overexpressing AtNHXl + SOS3, 50S2 + SOS3, or SOS1 + SOS2 +SOS3, respectively, appeared similar to the tolerance of transgenic plants overexpressing either SOS1 or SOS3 alone.

  6. Mitogen-activated protein kinase pathways contribute to hypercontractility and increased Ca2+ sensitization in murine experimental colitis.

    Science.gov (United States)

    Ihara, Eikichi; Beck, Paul L; Chappellaz, Mona; Wong, Josee; Medlicott, Shaun A; MacDonald, Justin A

    2009-05-01

    Inflammatory bowel disease (IBD) is associated with intestinal smooth muscle dysfunction. Many smooth muscle contractile events are associated with alterations in Ca(2+)-sensitizing pathways. The aim of the present study was to assess the effect of colitis on Ca(2+) sensitization and the signaling pathways responsible for contractile dysfunction in murine experimental colitis. Colitis was induced in BALB/c mice by providing 5% dextran sulfate sodium (DSS) in drinking water for 7 days. Contractile responses of colonic circular smooth muscle strips to 118 mM K(+) and carbachol (CCh) were assessed. DSS induced a T(H)2 colitis [increased interleukin (IL)-4 and IL-6] with no changes in T(H)1 cytokines. Animals exposed to DSS had increased CCh-induced contraction (3.5-fold) and CCh-induced Ca(2+)-sensitization (2.2-fold) responses in intact and alpha-toxin permeabilized colonic smooth muscle, respectively. The contributions of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) to CCh-induced contractions were significantly increased during colitis. Ca(2+)-independent contraction induced by microcystin was potentiated (1.5-fold) in mice with colitis. ERK and p38MAPK (but not Rho-associated kinase) contributed to this potentiation. ERK1/2 and p38MAPK expression were increased in the muscularis propria of colonic tissue from both DSS-treated mice and patients with IBD (ulcerative colitis > Crohn's disease). Murine T(H)2 colitis resulted in colonic smooth muscle hypercontractility with increased Ca(2+) sensitization. Both ERK and p38MAPK pathways contributed to this contractile dysfunction, and expression of these molecules was altered in patients with IBD.

  7. The Gas-Filled-Magnet at PRIME Lab: Increased Sensitivity of Cosmogenic Nuclide Measurements

    Science.gov (United States)

    Caffee, M. W.; Granger, D. E.; Woodruff, T. E.

    2015-12-01

    Abstract: Using accelerator mass spectrometry (AMS), radionuclides produced either by cosmic-ray interactions or by nucleogenic means can be measured. Typical isotopic abundance ratios range from 1 x 10-10 to 1 x 10-15. The routinely measured radionuclides are 10Be, 14C, 26Al, 36Cl, and 129I. Be-10, 26Al, and 36Cl have isobaric interferences that cannot be eliminated mass through mass analysis, but dE/dx techniques suppresses these isobars enough to allow successful measurements. There are compromises, the isobar for 26Al, 26Mg, precludes successful measurement of 26Al if AlO- is injected into the accelerator. Mg- doesn't form a stable negative ion so a 26Al measurement requires injection of 26Al-. But the Al- ion is formed inefficiently; secondary ion currents using Al- are ~ 10 times less than an AlO- secondary ion beam. Precision scales with count rate so precise measurement of the 26Al/Al for all but higher ratio samples is difficult. It has long been recognized that a gas-filled-magnet (GFM) could potentially improve the measurement of those radionuclides with intractable isobar interferences. A GFM works on the principle that each element of an isobar pair, e.g. 26Mg and 26Al, has a different average charge state as it traverses a gas (3-4 Torr of N2) contained within the vacuum jacket of a magnet. The magnet steers each species with its own momentum-to-charge ratio on its own distinct radius of curvature. The magnet can be tuned to allow the isotope of interest into a dE/dx detector; most of the isobar doesn't make it into the detector. Using the PRIME Lab GFM we are now able to routinely run 26Al with a precision that is comparable to that obtained with 10Be. We are also using the GFM for routine measurements of 10Be and 36Cl. Although the improvement for these nuclides is not as pronounced as it is for 26Al, the GFM has improved the detection sensitivity for both. Our 10Be background is now ~ 5 x 10-16 and for 36Cl we can now run the source more

  8. Cell cycle-arrested tumor cells exhibit increased sensitivity towards TRAIL-induced apoptosis

    OpenAIRE

    Ehrhardt, H.; Wachter, F; Grunert, M.; Jeremias, I

    2013-01-01

    Resting tumor cells represent a huge challenge during anticancer therapy due to their increased treatment resistance. TNF-related apoptosis-inducing ligand (TRAIL) is a putative future anticancer drug, currently in phases I and II clinical studies. We recently showed that TRAIL is able to target leukemia stem cell surrogates. Here, we tested the ability of TRAIL to target cell cycle-arrested tumor cells. Cell cycle arrest was induced in tumor cell lines and xenografted tumor cells in G0, G1 o...

  9. The R527H mutation in LMNA gene causes an increased sensitivity to ionizing radiation.

    Science.gov (United States)

    di Masi, Alessandra; D'Apice, Maria Rosaria; Ricordy, Ruggero; Tanzarella, Caterina; Novelli, Giuseppe

    2008-07-01

    Mandibuloacral dysplasia type A (MADA; OMIM # 248370) is a premature ageing disease caused by the homozygous R527H mutation in the LMNA gene. At the cellular level, MADA is characterized by unprocessed prelamin A accumulation, nuclear architecture alterations, chromatin defects and increased incidence of apoptosis. In some progeroid laminopathies (e.g., HGPS) it has been demonstrated that such biochemical and morphological alterations are strongly linked with genomic instability. To test this also in MADA fibroblasts, their response to the ionising radiation-induced damage was analysed. We observed that their ability to repair the damage was significantly impaired, as demonstrated by the increased chromosome damage and the higher percentage of residual gamma-H2AX foci, corresponding to unrepaired DNA-damage sites. Moreover, MADA fibroblasts showed a markedly reduced phosphorylation of p53 at Ser15(S15) and a lower induction of p53 and CDKN1A proteins after irradiation, compared to the control cell line. Upon irradiation, we also detected differences in the expression of some p53 downstream target genes. In addition, MADA cells showed partial defects in the checkpoint response, particularly in G(1)/S transition. Our results indicate that accumulation of the lamin A precursor protein determines a defect in DNA damage response after X-ray exposure, supporting a crucial role of lamin A in regulating DNA repair process and cell cycle control.

  10. Increase of insulin sensitivity in diabetic rats received Die-Huang-Wan, a herbal mixture used in Chinese traditional medicine

    Institute of Scientific and Technical Information of China (English)

    WU Yang-Chang; HSU Jen-Hao; LIU I-Min; LIOU Shorong-Shii; SU Hui-Chen; CHENG Juei-Tang

    2002-01-01

    AIM: Effects on insulin sensitivity of Die-Huang-Wan, the herbal mixture widely used to treat diabetic disorder in Chinese traditional medicine, were investigated in vivo. METHODS: The obese Zucker rats were employed as insulin-resistant animal model. Also, insulin-resistance was induced by the repeated intraperitoneal injections of long-acting human insulin at 0.5 U/kg three times daily into adult male Wistar rats. Insulin resistance was identified using the loss of tolbutamide (10 mg/kg) or electroacupuncture (EA)-induced plasma glucose lowering action. The plasma glucose concentration was examined by glucose oxidase assay. RESULTS: The plasma glucose-lowering action induced by tolbutamide was significantly enhanced in obese Zucker rats receiving the repeated administration of Die-Huang-Wan at dosage of 26 mg/kg for 3 d. Furthermore, administration of Die-Huang-Wan delayed the formation of insulin resistance in rats that were induced by the daily repeated injection of human long-acting insulin at 0.5 U/kg three times daily and identified by the loss of tolbutamide- or EA-induced hypoglycemia. In streptozotocininduced diabetic rats, oral administration of metformin at 320 mg/kg once daily made an increase of the response to exogenous short-acting human insulin 15 d later. This is consistent with the view that metformin can increase insulin sensitivity. Similar treatment with Die-Huang-Wan at an effective dose (26.0 mg/kg) also increased the plasma glucose lowering action of exogenous insulin at 10 d later. The effect of Die-Huang-Wan on insulin sensitivity seems to produce more rapidly than that of metformin. CONCLUSION: The present study found that oral administration of Die-Huang-Wan increased insulin sensitivity and delayed the development of insulin resistance in rats.

  11. Vitamin B6 deficient plants display increased sensitivity to high light and photo-oxidative stress

    Directory of Open Access Journals (Sweden)

    Rumeau Dominique

    2009-11-01

    Full Text Available Abstract Background Vitamin B6 is a collective term for a group of six interconvertible compounds: pyridoxine, pyridoxal, pyridoxamine and their phosphorylated derivatives. Vitamin B6 plays essential roles as a cofactor in a range of biochemical reactions. In addition, vitamin B6 is able to quench reactive oxygen species in vitro, and exogenously applied vitamin B6 protects plant cells against cell death induced by singlet oxygen (1O2. These results raise the important question as to whether plants employ vitamin B6 as an antioxidant to protect themselves against reactive oxygen species. Results The pdx1.3 mutation affects the vitamin B6 biosynthesis enzyme, pyridoxal synthase (PDX1, and leads to a reduction of the vitamin B6 concentration in Arabidopsis thaliana leaves. Although leaves of the pdx1.3 Arabidopsis mutant contained less chlorophyll than wild-type leaves, we found that vitamin B6 deficiency did not significantly impact photosynthetic performance or shoot and root growth. Chlorophyll loss was associated with an increase in the chlorophyll a/b ratio and a selective decrease in the abundance of several PSII antenna proteins (Lhcb1/2, Lhcb6. These changes were strongly dependent on light intensity, with high light amplifying the difference between pdx1.3 and the wild type. When leaf discs were exposed to exogenous 1O2, lipid peroxidation in pdx1.3 was increased relative to the wild type; this effect was not observed with superoxide or hydrogen peroxide. When leaf discs or whole plants were exposed to excess light energy, 1O2-mediated lipid peroxidation was enhanced in leaves of the pdx1.3 mutant relative to the wild type. High light also caused an increased level of 1O2 in vitamin B6-deficient leaves. Combining the pdx1.3 mutation with mutations affecting the level of 'classical' quenchers of 1O2 (zeaxanthin, tocopherols resulted in a highly photosensitive phenotype. Conclusion This study demonstrates that vitamin B6 has a function in

  12. Pandanus amaryllifolius leaf extract increases insulin sensitivity in high-fat diet-induced obese mice

    Institute of Scientific and Technical Information of China (English)

    Suphaket Saenthaweesuk; Jarinyaporn Naowaboot; Nuntiya Somparn

    2016-01-01

    Objective: To examine the effect of Pandanus amaryllifolius (P. amaryllifolius) leaf extract on the insulin resistance state in obese ICR mice. Methods: Obesity was induced in mice fed with high-fat diet (45%fat) for 12 weeks. After the first six weeks on the diet, the obese mice were administered with the water extract of P. amaryllifolius leaf at 125 and 250 mg/kg/day, respectively for another six weeks. At the 5th week of treatment, oral glucose tolerance test was conducted. After six weeks of treat-ment, the levels of blood glucose, serum insulin, leptin, adiponectin, and lipid profiles were determined. The liver, muscle and epididymal fat tissues were removed for measuring the biochemical parameters and protein expression, as well as histological examination. Results: Six weeks of treatment with P. amaryllifolius led to a significant reduction in the blood glucose level as well as improvement in the insulin resistance. P. amaryllifolius also increased the liver glycogen storage and serum adiponectin and decreased the serum leptin levels. A reduction in the serum and hepatic triglyceride, and non-esterified fatty acid levels was also observed. The histological examination showed that the obese mice treated with P. amaryllifolius reduced the lipid droplet in liver tissue and adipocyte size in epididymal fat tissue. The treatment also increased the protein expression of glucose transporter 4 in the muscle and fat tissues. Conclusions: The treatment with P. amaryllifolius could decrease several parameters of impaired glucose and lipid metabolism. To the best of our knowledge, this is the first report on the role of P. amaryllifolius leaf extract in alleviating the insulin dysfunction in obesity state.

  13. Increased sensitivity of apolipoprotein E knockout mice to copper-induced oxidative injury to the liver.

    Science.gov (United States)

    Chen, Yuan; Li, Bin; Zhao, Ran-ran; Zhang, Hui-feng; Zhen, Chao; Guo, Li

    2015-04-10

    Apolipoprotein E (ApoE) genotypes are related to clinical presentations in patients with Wilson's disease, indicating that ApoE may play an important role in the disease. However, our understanding of the role of ApoE in Wilson's disease is limited. High copper concentration in Wilson's disease induces excessive generation of free oxygen radicals. Meanwhile, ApoE proteins possess antioxidant effects. We therefore determined whether copper-induced oxidative damage differ in the liver of wild-type and ApoE knockout (ApoE(-/-)) mice. Both wild-type and ApoE(-/-) mice were intragastrically administered with 0.2 mL of copper sulfate pentahydrate (200 mg/kg; a total dose of 4 mg/d) or the same volume of saline daily for 12 weeks, respectively. Copper and oxidative stress markers in the liver tissue and in the serum were assessed. Our results showed that, compared with the wild-type mice administered with copper, TBARS as a marker of lipid peroxidation, the expression of oxygenase-1 (HO-1), NAD(P)H dehydrogenase, and quinone 1 (NQO1) significantly increased in the ApoE(-/-) mice administered with copper, meanwhile superoxide dismutase (SOD) activity significantly decreased. Thus, it is concluded that ApoE may protect the liver from copper-induced oxidative damage in Wilson's disease.

  14. Human cytomegalovirus increases HUVEC sensitivity to thrombin and modulates expression of thrombin receptors.

    Science.gov (United States)

    Popović, Milan; Paskas, Svetlana; Zivković, Maja; Burysek, Ladislav; Laumonnier, Yves

    2010-08-01

    Human cytomegalovirus (HCMV) establishes a life-long persistent infection. HCMV infection could be associated with chronic inflammatory diseases, such as cardiovascular disease and atherosclerosis. Here we observed that in HCMV (AD-169) pre-exposed human umbilical vein endothelial cells (HUVEC), thrombin-induced expression of IL-1alpha and M-CSF is markedly enhanced compared to the un-exposed cells. Study of the expression of thrombin receptor genes in HUVEC showed that HCMV triggered a time- and concentration-dependent expression of the thrombin receptors PAR1, PAR3 and PAR4 at the mRNA level. Induction of PAR1 and PAR3 mRNA expression is due to transcriptional activation of their promoters as shown by gene reporter assay. Furthermore, the virus induced expression of PAR1 and PAR3 but not PAR4 proteins, as analyzed by Western immunoblotting. However, flow cytometric analysis revealed that only PAR3, expressed at very low level in control HUVEC, is induced at the surface during the exposure to the virus. Our data suggest that although exposure to HCMV induces a minor increase of cell-surface receptors expression, it does make endothelial cells more responsive to additional thrombin stimulation.

  15. Soluble guanylate cyclase stimulators increase sensitivity to cisplatin in head and neck squamous cell carcinoma cells.

    Science.gov (United States)

    Tuttle, Traci R; Takiar, Vinita; Kumar, Bhavna; Kumar, Pawan; Ben-Jonathan, Nira

    2017-03-28

    Head and neck squamous cell carcinoma (HNSCC) is an aggressive and often fatal disease. Cisplatin is the most common chemotherapeutic drug in the treatment of HNSCC, but intrinsic and acquired resistance are frequent, and severe side effects occur at high doses. The second messenger cyclic GMP (cGMP) is produced by soluble guanylate cyclase (sGC). We previously reported that activation of the cGMP signaling cascade caused apoptosis in HNSCC cells, while others found that this pathway enhances cisplatin efficacy in some cell types. Here we found that sGC stimulators reduced HNSCC cell viability synergistically with cisplatin, and enhanced apoptosis by cisplatin. Moreover, the sGC stimulators effectively reduced viability in cells with acquired cisplatin resistance, and were synergistic with cisplatin. The sGC stimulator BAY 41-2272 reduced expression of the survival proteins EGFR and β-catenin, and increased pro-apoptotic Bax, suggesting a potential mechanism for the anti-tumorigenic effects of these drugs. The sGC stimulator Riociguat is FDA-approved to treat pulmonary hypertension, and others are being studied for therapeutic use in several diseases. These drugs could provide valuable addition or alternative to cisplatin in the treatment of HNSCC.

  16. In Vitro and Molecular Surveillance for Antimalarial Drug Resistance in Plasmodium falciparum Parasites in Western Kenya Reveals Sustained Artemisinin Sensitivity and Increased Chloroquine Sensitivity.

    Science.gov (United States)

    Lucchi, Naomi W; Komino, Franklin; Okoth, Sheila Akinyi; Goldman, Ira; Onyona, Philip; Wiegand, Ryan E; Juma, Elizabeth; Shi, Ya Ping; Barnwell, John W; Udhayakumar, Venkatachalam; Kariuki, Simon

    2015-12-01

    Malaria control is hindered by the evolution and spread of resistance to antimalarials, necessitating multiple changes to drug policies over time. A comprehensive antimalarial drug resistance surveillance program is vital for detecting the potential emergence of resistance to antimalarials, including current artemisinin-based combination therapies. An antimalarial drug resistance surveillance study involving 203 Plasmodium falciparum malaria-positive children was conducted in western Kenya between 2010 and 2013. Specimens from enrolled children were analyzed in vitro for sensitivity to chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ), lumefantrine, and artemisinin derivatives (artesunate and dihydroartemisinin) and for drug resistance allele polymorphisms in P. falciparum crt (Pfcrt), Pfmdr-1, and the K13 propeller domain (K13). We observed a significant increase in the proportion of samples with the Pfcrt wild-type (CVMNK) genotype, from 61.2% in 2010 to 93.0% in 2013 (P < 0.0001), and higher proportions of parasites with elevated sensitivity to CQ in vitro. The majority of isolates harbored the wild-type N allele in Pfmdr-1 codon 86 (93.5%), with only 7 (3.50%) samples with the N86Y mutant allele (the mutant nucleotide is underlined). Likewise, most isolates harbored the wild-type Pfmdr-1 D1246 allele (79.8%), with only 12 (6.38%) specimens with the D1246Y mutant allele and 26 (13.8%) with mixed alleles. All the samples had a single copy of the Pfmdr-1 gene (mean of 0.907 ± 0.141 copies). None of the sequenced parasites had mutations in K13. Our results suggest that artemisinin is likely to remain highly efficacious and that CQ sensitivity appears to be on the rise in western Kenya.

  17. Increased muscular and cutaneous pain sensitivity in cephalic region in patients with chronic tension-type headache.

    Science.gov (United States)

    Ashina, S; Babenko, L; Jensen, R; Ashina, M; Magerl, W; Bendtsen, L

    2005-07-01

    Increased excitability of the central nervous system generated by repetitive and sustained pericranial myofascial nociception may be responsible for transformation of episodic tension-type headache into chronic form. We aimed to compare mechanical and electrical (intramuscular and cutaneous) pain thresholds in trapezius and anterior tibial regions between 20 patients with chronic tension type headache and 20 healthy controls. Pain thresholds to three types of electrical stimulation (single pulse, 2 and 100 Hz) were significantly lower in patients than in controls in trapezius muscle (P tension-type headache than in healthy controls. Increased sensitivity in nociceptive pathways from cephalic region may be of importance in the pathophysiology of chronic tension type headache.

  18. Low-Level Fluoride Exposure Increases Insulin Sensitivity in Experimental Diabetes.

    Science.gov (United States)

    Lobo, J G V M; Leite, A L; Pereira, H A B S; Fernandes, M S; Peres-Buzalaf, C; Sumida, D H; Rigalli, A; Buzalaf, M A R

    2015-07-01

    The effect of chronic fluoride (F) exposure from the drinking water on parameters related to glucose homeostasis was investigated. Wistar rats were randomly distributed into 2 groups (diabetic [D] and nondiabetic [ND]; n = 54 each). In D, diabetes was induced with streptozotocin. Each group was further divided into 3 subgroups (0, 10, or 50 mgF/L in drinking water). After 22 days of treatment, plasma and liver samples were collected. No alterations in glycemia, insulinemia, K(ITT), and HOMA2-IR (homeostasis model assessment 2 of insulin resistance) were seen for ND. F-exposure of D rats led to significantly lower insulinemia, without alterations in glycemia (increased %S). Proteomic analysis detected 19, 39, and 16 proteins differentially expressed for the comparisons D0 vs. D10, D0 vs. D50, and D10 vs. D50, respectively. Gene Ontology with the most significant terms in the comparisons D0 vs. D10, D0 vs. D50, and D50 vs. D10 were organic acid metabolic process and carboxylic acid metabolic process, organic acid metabolic process, and cellular ketone metabolic process. Analysis of subnetworks revealed that proteins with fold changes interacted with GLUT4 in comparison D0 vs. D10. Among these proteins, ERj3p was present in D10. Upregulation of this protein in the presence of F might help to explain the higher %S found in these animals. These data suggest that fluoride might enhance glucose homeostasis in diabetes and identify specific biological mechanisms that merit future studies.

  19. Reduced fasting-induced activation of hypothalamic arcuate neurons is associated with hyperleptinemia and increased leptin sensitivity in obese mice.

    Science.gov (United States)

    Becskei, Csilla; Lutz, Thomas A; Riediger, Thomas

    2010-08-01

    Fasting increases c-Fos expression in neuropeptide Y (NPY) neurons of the hypothalamic arcuate nucleus (ARC) in lean, but not in hyperleptinemic mice with late-onset obesity (LOO). Although obesity is associated with leptin resistance, we hypothesized that under fasting conditions, leptin sensitivity might be restored and that hyperleptinemia may counteract the neuronal response to fasting. We investigated whether the reduced fasting response of ARC neurons in LOO is paralleled by an increase in leptin sensitivity, as measured by leptin-induced STAT-3 phosphorylation. To assess leptin's role in the modulation of the fasting-induced ARC activation, we investigated c-Fos responses and hormone and metabolite levels in hyperleptinemic diet-induced obese (DIO) and in leptin-deficient ob/ob mice. Leptin induced a stronger STAT-3 phosphorylation in fasted LOO and lean mice than in ad libitum-fed animals. Similar to LOO, hyperleptinemic DIO mice showed no c-Fos response after fasting, while ob/ob mice showed a stronger response than lean control mice. Mimicking hyperleptinemia by repeated leptin injections in lean mice during fasting attenuated the fasting-induced c-Fos expression. Our findings indicate that high leptin levels prevent the fasting-induced activation of ARC neurons in mice. Moreover, leptin sensitivity is dynamic in obese subjects and depends on the feeding status. During short-term increases in leptin sensitivity, e.g., during fasting, leptin signaling appears to be effective, even in hyperleptinemic obesity. As reflected by the blockade of the fasting-induced ARC activation, fasting seems to interfere with the responsiveness of the ARC to signals related to the status of energy intake.

  20. Jicama (Pachyrhizus erosus) extract increases insulin sensitivity and regulates hepatic glucose in C57BL/Ksj-db/db mice.

    Science.gov (United States)

    Park, Chan Joo; Lee, Hyun-Ah; Han, Ji-Sook

    2016-01-01

    This study investigated the effect of jicama extract on hyperglycemia and insulin sensitivity in an animal model of type 2 diabetes. Male C57BL/Ksj-db/db mice were divided into groups subsequently fed a regular diet (controls), or diet supplemented with jicama extract, and rosiglitazone. After 6 weeks, blood levels of glucose and glycosylated hemoglobin were significantly lower in animals administered the jicama extract than the control group. Additionally, glucose and insulin tolerance tests showed that jicama extract increased insulin sensitivity. The homeostatic index of insulin resistance was lower in the jicama extract-treated group than in the diabetic control group. Administration of jicama extract significantly enhanced the expressions of the phosphorylated AMP-activated protein kinase and Akt substrate of 160 kDa, and plasma membrane glucose transporter type 4 in skeletal muscle. Jicama extract administration also decreased the expressions of glucose 6-phosphatase and phosphoenol pyruvate carboxykinase in the liver. Jicama extract may increases insulin sensitivity and inhibites the gluconeogenesis in the liver.

  1. Loss of lingual sensitivity and slightly increased size signaling schwannoma in a patient with mixed conjunctive tissue disease.

    Science.gov (United States)

    Ferreira, D C; Nogueira, G; Cancio, V A; Cavalcante, F S; Godefroy, P; Sousa, D S C; Hespanhol, W; dos Santos, K R N; Cavalcante, M A B

    2013-01-01

    The purpose of this study was to describe an unusual case of a lingual schwannoma associated with a mixed connective tissue disease (MCTD). A case report. A lingual schwannoma with loss of lingual sensitivity and slightly increased size in an 18-year-old patient with MCTD was correctly diagnosed through a biopsy and no reoccurrence was observed one year after the surgical removal of the tumor and sensitivity returned 3 months after surgery. This case was considered uncommon, making the clinical diagnosis challenging in view of the diversity of possibilities for its differential diagnosis, thus showing the importance of a biopsy to confirm the diagnosis and long term follow up in such cases.

  2. Pretreatment with mixed-function oxidase inducers increases the sensitivity of the hepatocyte/DNA repair assay

    Energy Technology Data Exchange (ETDEWEB)

    Shaddock, J.G.; Heflich, R.H.; McMillan, D.C.; Hinson, J.A.; Casciano, D.A. (National Center for Toxicological Research, Jefferson, AK (USA) Univ. of Arkansas for Medical Sciences, Little Rock (USA))

    1989-01-01

    A recent National Toxicology Program evaluation indicates that the rat hepatocyte/DNA repair assay has a high false-negative rate and that it is insensitive to some genotoxic hepatocarcinogens as well as other species and organ-specific carcinogens. In this study, the authors examined whether the sensitivity of the hepatocyte/DNA repair assay might be increased through animal pretreatment with various hepatic mixed-function oxidase inducers, i.e., Aroclor 1254, phenobarbital, and 3,3{prime},4,4{prime}-tetrachloroazobenzene (TCAB). The effects on unscheduled DNA synthesis (UDS), a measured of DNA damage and repair, were studied in cultures exposed to known and/or potential carcinogens that had been evaluated as negative or questionable or that produced conflicting results with hepatocytes isolated from uninduced animals. 4,4{prime}-Oxydianiline, 1-nitropy-rene, and TCAB produced concentration-dependent increases in UDS in hepatocytes from rats pretreated with Aroclor 1254. 4,4{prime}-Oxydianiline and TCAB also induced a dose-dependent increase in DNA repair in hepatocytes from rats pretreated with phenobarbital, whereas 1-nitropyrene was negative. These data indicate that the limited sensitivity to chemical carcinogens displayed by the hepatocyte/DNA repair assay may be increased by using hepatocytes isolated from animals exposed to hepatic mixed-function oxidase inducers.

  3. Increasing the Depth of Current Understanding: Sensitivity Testing of Deep-Sea Larval Dispersal Models for Ecologists

    Science.gov (United States)

    Nimmo-Smith, W. Alex M.; Howell, Kerry L.

    2016-01-01

    Larval dispersal is an important ecological process of great interest to conservation and the establishment of marine protected areas. Increasing numbers of studies are turning to biophysical models to simulate dispersal patterns, including in the deep-sea, but for many ecologists unassisted by a physical oceanographer, a model can present as a black box. Sensitivity testing offers a means to test the models’ abilities and limitations and is a starting point for all modelling efforts. The aim of this study is to illustrate a sensitivity testing process for the unassisted ecologist, through a deep-sea case study example, and demonstrate how sensitivity testing can be used to determine optimal model settings, assess model adequacy, and inform ecological interpretation of model outputs. Five input parameters are tested (timestep of particle simulator (TS), horizontal (HS) and vertical separation (VS) of release points, release frequency (RF), and temporal range (TR) of simulations) using a commonly employed pairing of models. The procedures used are relevant to all marine larval dispersal models. It is shown how the results of these tests can inform the future set up and interpretation of ecological studies in this area. For example, an optimal arrangement of release locations spanning a release area could be deduced; the increased depth range spanned in deep-sea studies may necessitate the stratification of dispersal simulations with different numbers of release locations at different depths; no fewer than 52 releases per year should be used unless biologically informed; three years of simulations chosen based on climatic extremes may provide results with 90% similarity to five years of simulation; and this model setup is not appropriate for simulating rare dispersal events. A step-by-step process, summarising advice on the sensitivity testing procedure, is provided to inform all future unassisted ecologists looking to run a larval dispersal simulation. PMID

  4. Increasing the Depth of Current Understanding: Sensitivity Testing of Deep-Sea Larval Dispersal Models for Ecologists.

    Science.gov (United States)

    Ross, Rebecca E; Nimmo-Smith, W Alex M; Howell, Kerry L

    2016-01-01

    Larval dispersal is an important ecological process of great interest to conservation and the establishment of marine protected areas. Increasing numbers of studies are turning to biophysical models to simulate dispersal patterns, including in the deep-sea, but for many ecologists unassisted by a physical oceanographer, a model can present as a black box. Sensitivity testing offers a means to test the models' abilities and limitations and is a starting point for all modelling efforts. The aim of this study is to illustrate a sensitivity testing process for the unassisted ecologist, through a deep-sea case study example, and demonstrate how sensitivity testing can be used to determine optimal model settings, assess model adequacy, and inform ecological interpretation of model outputs. Five input parameters are tested (timestep of particle simulator (TS), horizontal (HS) and vertical separation (VS) of release points, release frequency (RF), and temporal range (TR) of simulations) using a commonly employed pairing of models. The procedures used are relevant to all marine larval dispersal models. It is shown how the results of these tests can inform the future set up and interpretation of ecological studies in this area. For example, an optimal arrangement of release locations spanning a release area could be deduced; the increased depth range spanned in deep-sea studies may necessitate the stratification of dispersal simulations with different numbers of release locations at different depths; no fewer than 52 releases per year should be used unless biologically informed; three years of simulations chosen based on climatic extremes may provide results with 90% similarity to five years of simulation; and this model setup is not appropriate for simulating rare dispersal events. A step-by-step process, summarising advice on the sensitivity testing procedure, is provided to inform all future unassisted ecologists looking to run a larval dispersal simulation.

  5. Increasing Superoxide Production and the Labile Iron Pool in Tumor Cells May Sensitize Them to Extracellular Ascorbate

    Directory of Open Access Journals (Sweden)

    Mark Frederick Mccarty

    2014-09-01

    Full Text Available Low millimolar concencentrations of ascorbate are capable of inflicting lethal damage on a high proportion of cancer cells lines, yet leave non-transformed cell lines unscathed; extracellular generation of hydrogen peroxide, reflecting reduction of molecular oxygen by ascorbate, has been shown to mediate this effect. Although some cancer cell lines express low catalase activity, this cannot fully explain the selective sensitivity of cancer cells to hydrogen peroxide. Ranzato and colleagues have presented evidence for a plausible new explanation of this sensitivity - a high proportion of cancers, via NADPH oxidase complexes or dysfunctional mitochondria, produce elevated amounts of superoxide. This superoxide, via a transition metal-catalyzed transfer of an electron to the hydrogen peroxide produced by ascorbate, can generate deadly hydroxyl radical (Haber-Weiss reaction. It thus can be predicted that concurrent measures which somewhat selectively boost superoxide production in cancers will enhance their sensitivity to i.v. ascorbate therapy. One way to achieve this is to increase the provision of substrate to cancer mitochondria. Measures which inhibit the constitutive hypoxia-inducible factor-1 (HIF-1 activity in cancers (such as salsalate and mTORC1 inhibitors, or an improvement of tumor oxygenation, or that inhibit the HIF-1-inducible pyruvate dehydrogenase kinase (such as dichloroacetate, can be expected to increase pyruvate oxidation. A ketogenic diet should provide more lipid substrate for tumor mitochondria. The cancer-killing activity of 42°C hyperthermia is to some degree contingent on an increase in oxidative stress, likely of mitochondrial origin; reports that hydrogen peroxide synergizes with hyperthermia in killing cancer cells suggest that hyperthermia and i.v. ascorbate could potentiate each other’s efficacy. A concurrent enhancement of tumor oxygenation might improve results by decreasing HIF-1 activity while increasing the

  6. Passive sensitization increases histamine-stimulated calcium signaling and NF-кB transcription activity in bronchial epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Si JIN; Dan TIAN; Jian-guo CHEN; Li-ping ZHU; Sheng-yuan LIU; Di-xun WANG

    2006-01-01

    Aim: To find out if the two aspects of asthma (chronic airway inflammation and bronchial hyperresponsiveness) are related to hypersensitivity of calcium signaling in bronchial epithelial cells. Methods: Porcine bronchial epithelial cells (PBEC) were divided into sensitized (S) and nonsesitized (N) groups. In group S, the cells were preincubated with serum from ovalbumin sensitized guinea pigs. In group N, the cells were preincubated with serum from nonsensitized guinea pigs. Single cell calcium imaging and ELISA-based NF-κB activity were used to evaluate the histamine-stimulated intracellular free calcium level and NF-κB activity, respectively. Results: First, 0.1 umol/L histamine could induce [Ca2+]i oscillations in PBEC of group S, but not in group N. Second, 1 umol/L histamine could induce [Ca2+]i oscillations of PBEC in both group S and group N. The [Ca2+]i oscillation frequency of PBEC was significantly higher in group S than in group N, though the [Ca2+]i oscillation amplitude showed no difference between the two groups. Finally, when 10 umol/L histamine was used to stimulate PBEC, a transient initial increase followed by a sustained elevation (FSE) of [Ca2+]i was observed in PBEC in both groups. The amplitude of the FSE of [Ca2+]i in PBEC was significantly higher in group S than in group N. The subsequent NF-KB activity was in accordance to the calcium oscillation frequency evoked by histamine, but not to the amplitude. Conclusion: It was suggested that the increased sensitivity of calcium signaling in bronchial epithelial cells might contribute to the exorbitant inflammation or increased susceptibility in asthmatic airway epithelial cells.

  7. Usage of Leptospira spp. local strains as antigens increases the sensitivity of the serodiagnosis of bovine leptospirosis.

    Science.gov (United States)

    Pinto, Priscila S; Loureiro, Ana P; Penna, Bruno; Lilenbaum, Walter

    2015-09-01

    Leptospirosis is a zoonotic disease that occurs worldwide, particularly in tropical countries. In livestock the agent is responsible for reproductive problems such as infertility and abortion. Serogroup Sejroe, particularly serovar Hardjo, prevails in cattle in several regions. The microscopic agglutination test (MAT) is the current method for diagnosing leptospirosis. It has been proposed that the inclusion of local strains could detect a larger set of seroreactive animals. In that context, the aim of the present study was to evaluate if the usage of local strains as antigens increases the sensitivity of the serodiagnosis of bovine leptospirosis. Blood and urine samples were collected from 314 bovines from several herds randomly selected in a slaughterhouse in Rio de Janeiro, Brazil. Serological diagnosis was made with MAT using a 21 reference-strains panel (MAT21). Additionally, 12 local strains (MAT33) were included as antigens. PCR was performed with the urine samples and it was positive on 71 out of 222 samples (31.9%). MAT21 identified as seroreactive 173 (55.1%) out of the 314 animals studied, with Sejroe the most common (38.1%). In MAT33, 204 (65.0%) animals were seroreactive with a significant increase on seroreactivity (9.9%). In conclusion, MAT presented with a significant increase of sensitivity when local strains were used as antigens. Among the local strains, 2013_U152 (KP263062) (serogroup Shermani) and 2013_U280 (KP263069) (serogroup Grippotyphosa) showed to be more antigenic.

  8. Loss of the N-terminal methyltransferase NRMT1 increases sensitivity to DNA damage and promotes mammary oncogenesis

    Science.gov (United States)

    Bonsignore, Lindsay A.; Butler, Jill Sergesketter; Klinge, Carolyn M.; Tooley, Christine E. Schaner

    2015-01-01

    Though discovered over four decades ago, the function of N-terminal methylation has mostly remained a mystery. Our discovery of the first mammalian N-terminal methyltransferase, NRMT1, has led to the discovery of many new functions for N-terminal methylation, including regulation of DNA/protein interactions, accurate mitotic division, and nucleotide excision repair (NER). Here we test whether NRMT1 is also important for DNA double-strand break (DSB) repair, and given its previously known roles in cell cycle regulation and the DNA damage response, assay if NRMT1 is acting as a tumor suppressor. We find that NRMT1 knockdown significantly enhances the sensitivity of breast cancer cell lines to both etoposide treatment and γ-irradiation, as well as, increases proliferation rate, invasive potential, anchorage-independent growth, xenograft tumor size, and tamoxifen sensitivity. Interestingly, this positions NRMT1 as a tumor suppressor protein involved in multiple DNA repair pathways, and indicates, similar to BRCA1 and BRCA2, its loss may result in tumors with enhanced sensitivity to diverse DNA damaging chemotherapeutics. PMID:25909287

  9. Increasing Superoxide Production and the Labile Iron Pool in Tumor Cells may Sensitize Them to Extracellular Ascorbate.

    Science.gov (United States)

    McCarty, Mark Frederick; Contreras, Francisco

    2014-01-01

    Low millimolar concentrations of ascorbate are capable of inflicting lethal damage on a high proportion of cancer cells lines, yet leave non-transformed cell lines unscathed. Extracellular generation of hydrogen peroxide, reflecting reduction of molecular oxygen by ascorbate, has been shown to mediate this effect. Although some cancer cell lines express low catalase activity, this cannot fully explain the selective sensitivity of cancer cells to hydrogen peroxide. Ranzato and colleagues have presented evidence for a plausible new explanation of this sensitivity - a high proportion of cancers, via NADPH oxidase complexes or dysfunctional mitochondria, produce elevated amounts of superoxide. This superoxide, via a transition metal-catalyzed transfer of an electron to the hydrogen peroxide produced by ascorbate, can generate deadly hydroxyl radical (Haber-Weiss reaction). It thus can be predicted that concurrent measures which somewhat selectively boost superoxide production in cancers will enhance their sensitivity to i.v. ascorbate therapy. One way to achieve this is to increase the provision of substrate to cancer mitochondria. Measures which inhibit the constitutive hypoxia-inducible factor-1 (HIF-1) activity in cancers (such as salsalate and mTORC1 inhibitors, or an improvement of tumor oxygenation), or that inhibit the HIF-1-inducible pyruvate dehydrogenase kinase (such as dichloroacetate), can be expected to increase pyruvate oxidation. A ketogenic diet should provide more lipid substrate for tumor mitochondria. The cancer-killing activity of 42°C hyperthermia is to some degree contingent on an increase in oxidative stress, likely of mitochondrial origin; reports that hydrogen peroxide synergizes with hyperthermia in killing cancer cells suggest that hyperthermia and i.v. ascorbate could potentiate each other's efficacy. A concurrent enhancement of tumor oxygenation might improve results by decreasing HIF-1 activity while increasing the interaction of ascorbic

  10. Zerumbone inhibits growth of hormone refractory prostate cancer cells by inhibiting JAK2/STAT3 pathway and increases paclitaxel sensitivity.

    Science.gov (United States)

    Jorvig, Jessica E; Chakraborty, Arup

    2015-02-01

    Zerumbone, a phytochemical isolated from Zingiber zerumbet has been shown previously to exhibit antineoplastic activity. But, the effect of zerumbone in prostate cancer has not been evaluated. Prostate cancer is frequently associated with elevated levels of interleukin-6 (IL-6), which exerts its oncogenic effects through activation of Janus kinase 2 (JAK2) followed by activation of the transcription factor STAT3 (signal transducer and activator of transcription 3). Here, we investigated whether the anticancer effects of zerumbone are mediated through inhibition of the JAK2/STAT3 signaling pathway and whether zerumbone can increase the paclitaxel (PTX) sensitivity of prostate cancer cells. Zerumbone exerted significant cytotoxicity of DU145 versus PC3 prostate cancer cells through cell cycle arrest at G0/G1 phase followed by apoptosis. Zerumbone selectively inhibited JAK2 in both DU145 and PC3 cells. However, the biological axis of IL-6/JAK2/STAT3 was inhibited only in DU145 cells as no STAT3 phosphorylation was detected in PC3 cells even after IL-6 stimulation. Other signaling pathways in DU145 cells remained unaffected. The expression of prostate cancer-associated genes, including cyclin D1, IL-6, COX2, and ETV1, was blocked. Zerumbone also synergistically increased the sensitivity to PTX. Further preclinical study might reveal the potential use of zerumbone as a chemotherapeutic agent for hormone refractory prostate cancer where IL-6/JAK2/STAT3 signaling is aberrantly active and may be combined with PTX.

  11. Transforming growth factor beta receptor 1 is increased following abstinence from cocaine self-administration, but not cocaine sensitization.

    Directory of Open Access Journals (Sweden)

    Amy M Gancarz-Kausch

    Full Text Available The addicted phenotype is characterized as a long-lasting, chronically relapsing disorder that persists following long periods of abstinence, suggesting that the underlying molecular changes are stable and endure for long periods even in the absence of drug. Here, we investigated Transforming Growth Factor-Beta Type I receptor (TGF-β R1 expression in the nucleus accumbens (NAc following periods of withdrawal from cocaine self-administration (SA and a sensitizing regimen of non-contingent cocaine. Rats were exposed to either (i repeated systemic injections (cocaine or saline, or (ii self-administration (cocaine or saline and underwent a period of forced abstinence (either 1 or 7 days of drug cessation. Withdrawal from cocaine self-administration resulted in an increase in TGF-β R1 protein expression in the NAc compared to saline controls. This increase was specific for volitional cocaine intake as no change in expression was observed following a sensitizing regimen of experimenter-administered cocaine. These findings implicate TGF-β signaling as a novel potential therapeutic target for treating drug addiction.

  12. International kidney paired donation transplantations to increase kidney transplant of O group and highly sensitized patient: First report from India

    Science.gov (United States)

    Kute, Vivek B; Patel, Himanshu V; Shah, Pankaj R; Modi, Pranjal R; Shah, Veena R; Rizvi, Sayyed J; Pal, Bipin C; Shah, Priya S; Wakhare, Pavan S; Shinde, Saiprasad G; Ghodela, Vijay A; Varyani, Umesh T; Patel, Minaxi H; Trivedi, Varsha B; Trivedi, Hargovind L

    2017-01-01

    AIM To report the first international living related two way kidney paired donation (KPD) transplantation from India which occurred on 17th February 2015 after legal permission from authorization committee. METHODS Donor recipient pairs were from Portugal and India who were highly sensitized and ABO incompatible with their spouse respectively. The two donor recipient pairs had negative lymphocyte cross-matching, flow cross-match and donor specific antibody in two way kidney exchange with the intended KPD donor. Local KPD options were fully explored for Indian patient prior to embarking on international KPD. RESULTS Both pairs underwent simultaneous uneventful kidney transplant surgeries and creatinine was 1 mg/dL on tacrolimus based immunosuppression at 11 mo follow up. The uniqueness of these transplantations was that they are first international KPD transplantations in our center. CONCLUSION International KPD will increases quality and quantity of living donor kidney transplantation. This could be an important step to solving the kidney shortage with additional benefit of reduced costs, improved quality and increased access for difficult to match incompatible pairs like O blood group patient with non-O donor and sensitized patient. To the best of our knowledge this is first international KPD transplantation from India. PMID:28280697

  13. Antisense bcl-2 retrovirus vector increases the sensitivity of a human gastric adenocarcinoma cell line to photodynamic therapy.

    Science.gov (United States)

    Zhang, W G; Ma, L P; Wang, S W; Zhang, Z Y; Cao, G D

    1999-05-01

    The bcl-2 oncoprotein directly prolongs cellular survival by blocking apoptosis and its overexpression is associated with cellular resistance to killing by chemotherapeutic drugs and gamma-irradiation. Meanwhile, it has been shown that bcl-2 antisense oligonucleotide can induce apoptosis or increase toxicity of the treatment in tumors in vivo and in vitro. However, it is difficult to obtain stable transfection by this approach and there are no reports about the effect of an antisense bcl-2 on the sensitivity to oxidative stress induced by photodynamic therapy (PDT). Here we investigated the effect of an antisense bcl-2 RNA retrovirus vector transfer on the sensitivity of 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA) photosensitization in a human gastric adenocarcinoma MGC803 cell line. The results indicate that antisense bcl-2-infected MGC803 cells expressed exogenous antisense bcl-2 mRNA measured by reverse transcription polymerase chain reaction and significantly reduced bcl-2 protein determined by western blotting analysis. The decreased expression of bcl-2 protein was accompanied by increased phototoxicity and susceptibility to apoptosis induced by 2-BA-2-DMHA PDT. Our finding suggests that reduction of bcl-2 protein in gastric cancers, and possibly also in a variety of other tumors, may be a novel and rational approach to improve photosensitivity and the treatment outcome.

  14. Increasing the Analytical Sensitivity by Oligonucleotides Modified with Para- and Ortho-Twisted Intercalating Nucleic Acids - TINA

    DEFF Research Database (Denmark)

    Schneider, Uffe V; Géci, Imrich; Jøhnk, Nina;

    2011-01-01

    The sensitivity and specificity of clinical diagnostic assays using DNA hybridization techniques are limited by the dissociation of double-stranded DNA (dsDNA) antiparallel duplex helices. This situation can be improved by addition of DNA stabilizing molecules such as nucleic acid intercalators....... Here, we report the synthesis of a novel ortho-Twisted Intercalating Nucleic Acid (TINA) amidite utilizing the phosphoramidite approach, and examine the stabilizing effect of ortho- and para-TINA molecules in antiparallel DNA duplex formation. In a thermal stability assay, ortho- and para......-TINA molecules increased the melting point (Tm) of Watson-Crick based antiparallel DNA duplexes. The increase in Tm was greatest when the intercalators were placed at the 5' and 3' termini (preferable) or, if placed internally, for each half or whole helix turn. Terminally positioned TINA molecules improved...

  15. Increased sensitivity to thermal pain following a single opiate dose is influenced by the COMT val(158met polymorphism.

    Directory of Open Access Journals (Sweden)

    Karin B Jensen

    Full Text Available Increased pain sensitivity after opioid administration (opioid-induced hyperalgesia and/or repeated painful stimuli is an individually varying and clinically important phenomenon. The functional polymorphism (val(158met of the Catechol-O-methyltransferase (COMT gene regulates the metabolism of dopamine/noradrenaline. Individuals homozygous for the met(158 allele have been reported to have increased pain sensitivity and there are findings of lower micro-opioid system activation during sustained pain. We hypothesized that met/met individuals would exhibit higher pain sensitization and opioid-induced hyperalgesia in response to repeated pain stimuli and an intravenous injection of an opioid drug. Participants were 43 healthy subjects who went through an experiment where five blocks of pain were induced to the hand using a heat probe. After each stimulus subjects rated the pain on a visual analogue scale (VAS from 0 mm (no pain to 100 mm (worst possible pain. Before the second stimulus there was an intravenous injection of a rapid and potent opioid drug. At baseline there was no difference in pain ratings between the COMTval(158met genotypes, F(2, 39<1. However, a repeated measures ANOVA for all five stimuli revealed a main effect for COMTval(158met genotype, F(2, 36 = 4.17, p = 0.024. Met/met individuals reported significantly more pain compared to val/val, p = 0.010. A pairwise comparison of baseline and the opioid intervention demonstrated that analgesia was induced in all groups (p = 0.042 without a separating effect for genotype (n.s. We suggest that the initial response of the descending pain system is not influenced by the COMTval(158met polymorphism but when the system is challenged the difference is revealed. An important clinical implication of this may be that the COMTval(158met related differences may be more expressed in individuals where the inhibitory system is already challenged and sensitive, e.g. chronic pain patients. This has to

  16. Increased androgenic sensitivity in the hind limb muscular system marks the evolution of a derived gestural display

    Science.gov (United States)

    Mangiamele, Lisa A.; Fuxjager, Matthew J.; Schuppe, Eric R.; Taylor, Rebecca S.; Hödl, Walter; Preininger, Doris

    2016-01-01

    Physical gestures are prominent features of many species’ multimodal displays, yet how evolution incorporates body and leg movements into animal signaling repertoires is unclear. Androgenic hormones modulate the production of reproductive signals and sexual motor skills in many vertebrates; therefore, one possibility is that selection for physical signals drives the evolution of androgenic sensitivity in select neuromotor pathways. We examined this issue in the Bornean rock frog (Staurois parvus, family: Ranidae). Males court females and compete with rivals by performing both vocalizations and hind limb gestural signals, called “foot flags.” Foot flagging is a derived display that emerged in the ranids after vocal signaling. Here, we show that administration of testosterone (T) increases foot flagging behavior under seminatural conditions. Moreover, using quantitative PCR, we also find that adult male S. parvus maintain a unique androgenic phenotype, in which androgen receptor (AR) in the hind limb musculature is expressed at levels ∼10× greater than in two other anuran species, which do not produce foot flags (Rana pipiens and Xenopus laevis). Finally, because males of all three of these species solicit mates with calls, we accordingly detect no differences in AR expression in the vocal apparatus (larynx) among taxa. The results show that foot flagging is an androgen-dependent gestural signal, and its emergence is associated with increased androgenic sensitivity within the hind limb musculature. Selection for this novel gestural signal may therefore drive the evolution of increased AR expression in key muscles that control signal production to support adaptive motor performance. PMID:27143723

  17. Increased pressure-induced tone in rat parenchymal arterioles vs. middle cerebral arteries: role of ion channels and calcium sensitivity.

    Science.gov (United States)

    Cipolla, Marilyn J; Sweet, Julie; Chan, Siu-Lung; Tavares, Matthew J; Gokina, Natalia; Brayden, Joseph E

    2014-07-01

    Brain parenchymal arterioles (PAs) are high-resistance vessels that branch off pial arteries and perfuse the brain parenchyma. PAs are the target of cerebral small vessel disease and have been shown to have greater pressure-induced tone at lower pressures than pial arteries. We investigated mechanisms by which brain PAs have increased myogenic tone compared with middle cerebral arteries (MCAs), focusing on differences in vascular smooth muscle (VSM) calcium and ion channel function. The amount of myogenic tone and VSM calcium was measured using Fura 2 in isolated and pressurized PAs and MCAs. Increases in intraluminal pressure caused larger increases in tone and cytosolic calcium in PAs compared with MCAs. At 50 mmHg, myogenic tone was 37 ± 5% for PAs vs. 6.5 ± 4% for MCAs (P channel (VDCC) inhibitor nifedipine than MCAs (EC50 for PAs was 3.5 ± 0.4 vs. 82.1 ± 2.1 nmol/l for MCAs;P channel inhibitor iberiotoxin, whereas MCAs constricted ∼15%. Thus increased myogenic tone in PAs appears related to differences in ion channel activity that promotes VSM membrane depolarization but not to a direct sensitization of the contractile apparatus to calcium.

  18. Fluorescent Probe Encapsulated in SNAP-Tag Protein Cavity To Eliminate Nonspecific Fluorescence and Increase Detection Sensitivity.

    Science.gov (United States)

    Zeng, Yan-Syun; Gao, Ruo-Cing; Wu, Ting-Wei; Cho, Chien; Tan, Kui-Thong

    2016-08-17

    Despite the promising improvements made recently on fluorescence probes for the detection of enzymes and reactive small molecules, two fundamental problems remain: weaker fluorescence of many dyes in aqueous buffers and strong nonspecific signals in samples containing high protein levels. In this paper, we introduce a novel fluorescent probe encapsulated in protein cavity (FPEPC) concept as demonstrated by SNAP-tag protein and three environment-sensitive fluorescence probes to overcome these two problems. The probes were constructed by following the current probe design for enzymes and reactive small molecules but with an additional benzylguanine moiety for selective SNAP-tag conjugation. The SNAP-tag conjugated probes achieved quantitative nitroreductase and hydrogen sulfide detection in blood plasma, whereas analyte concentrations were overestimated up to 700-fold when bare fluorescent probes were employed for detection. Furthermore, detection sensitivity was increased dramatically, as our probes displayed 390-fold fluorescence enhancement upon SNAP-tag conjugation, in stark contrast to the weak fluorescence of the free probes in aqueous solutions. Compared with the conventional approaches where fluorescent probes are encapsulated into polymers and nanoparticles, our simple and general approach successfully overcame many key issues such as dye leakage, long preparation steps, inconsistent dye-host ratios, difficulty in constructing in situ in a complex medium, and limited application to detect only small metabolites.

  19. Prep1 deficiency induces protection from diabetes and increased insulin sensitivity through a p160-mediated mechanism.

    Science.gov (United States)

    Oriente, Francesco; Fernandez Diaz, Luis Cesar; Miele, Claudia; Iovino, Salvatore; Mori, Silvia; Diaz, Victor Manuel; Troncone, Giancarlo; Cassese, Angela; Formisano, Pietro; Blasi, Francesco; Beguinot, Francesco

    2008-09-01

    We have examined glucose homeostasis in mice hypomorphic for the homeotic transcription factor gene Prep1. Prep1-hypomorphic (Prep1(i/i)) mice exhibit an absolute reduction in circulating insulin levels but normal glucose tolerance. In addition, these mice exhibit protection from streptozotocin-induced diabetes and enhanced insulin sensitivity with improved glucose uptake and insulin-dependent glucose disposal by skeletal muscle. This muscle phenotype does not depend on reduced expression of the known Prep1 transcription partner, Pbx1. Instead, in Prep1(i/i) muscle, we find normal Pbx1 but reduced levels of the recently identified novel Prep1 interactor p160. Consistent with this reduction, we find a muscle-selective increase in mRNA and protein levels of PGC-1alpha, accompanied by enhanced expression of the GLUT4 transporter, responsible for insulin-stimulated glucose uptake in muscle. Indeed, using L6 skeletal muscle cells, we induced the opposite effects by overexpressing Prep1 or p160, but not Pbx1. In vivo skeletal muscle delivery of p160 cDNA in Prep1(i/i) mice also reverses the molecular phenotype. Finally, we show that Prep1 controls the stability of the p160 protein. We conclude that Prep1 controls insulin sensitivity through the p160-GLUT4 pathway.

  20. Curcumin-Mediated HDAC Inhibition Suppresses the DNA Damage Response and Contributes to Increased DNA Damage Sensitivity.

    Directory of Open Access Journals (Sweden)

    Shu-Huei Wang

    Full Text Available Chemo- and radiotherapy cause multiple forms of DNA damage and lead to the death of cancer cells. Inhibitors of the DNA damage response are candidate drugs for use in combination therapies to increase the efficacy of such treatments. In this study, we show that curcumin, a plant polyphenol, sensitizes budding yeast to DNA damage by counteracting the DNA damage response. Following DNA damage, the Mec1-dependent DNA damage checkpoint is inactivated and Rad52 recombinase is degraded by curcumin, which results in deficiencies in double-stand break repair. Additive effects on damage-induced apoptosis and the inhibition of damage-induced autophagy by curcumin were observed. Moreover, rpd3 mutants were found to mimic the curcumin-induced suppression of the DNA damage response. In contrast, hat1 mutants were resistant to DNA damage, and Rad52 degradation was impaired following curcumin treatment. These results indicate that the histone deacetylase inhibitor activity of curcumin is critical to DSB repair and DNA damage sensitivity.

  1. miR-181b increases drug sensitivity in acute myeloid leukemia via targeting HMGB1 and Mcl-1.

    Science.gov (United States)

    Lu, Fei; Zhang, Jingru; Ji, Min; Li, Peng; Du, Yahui; Wang, Hongchun; Zang, Shaolei; Ma, Daoxin; Sun, Xiulian; Ji, Chunyan

    2014-07-01

    Multidrug resistance (MDR) remains the major cause of disease relapse and poor prognosis in adults with acute myeloid leukemia (AML). Emerging evidence shows that drug resistance not only exists against conventional chemotherapeutic drugs, but also limits the efficacy of new biological agents. Therefore, it is important to elucidate the mechanisms through which AML patients develop drug resistance. MicroRNAs have been shown to play an important role in regulating the chemotherapy resistance in AML. A detailed understanding of the mechanisms of microRNA that are clinically relevant in AML may enhance our ability to predict and overcome drug resistance. Here, we demonstrated, for the first time, that miR-181b was decreased significantly in human multidrug-resistant leukemia cells and relapsed/refractory AML patient samples. Overexpression of miR-181b increased the sensitivity of leukemia cells to cytotoxic chemotherapeutic agents and promoted drug-induced apoptosis. Moreover, miR-181b inhibited HMGB1 and Mcl-1 expression by direct binding to their 3'-untranslated regions. In addition, HMGB1 was expressed at high levels in relapsed/refractory AML patients and suppression of HMGB1 via RNA interference sensitized multidrug-resistant leukemia cells to chemotherapy and induced apoptosis. In conclusion, these results provide a strong rationale for the development of miR-181b-based therapeutic strategies for the enhancement of efficacy in AML treatment.

  2. IDH1R132H Mutation Increases U87 Glioma Cell Sensitivity to Radiation Therapy in Hypoxia

    Science.gov (United States)

    Wang, Xiao-Wei; Labussière, Marianne; Valable, Samuel; Pérès, Elodie A.; Guillamo, Jean-Sébastien; Sanson, Marc

    2014-01-01

    Objective. IDH1 codon 132 mutation (mostly Arg132His) is frequently found in gliomas and is associated with longer survival. However, it is still unclear whether IDH1 mutation renders the cell more vulnerable to current treatment, radio- and chemotherapy. Materials and Methods. We transduced U87 with wild type IDH1 or IDH1R132H expressing lentivirus and analyzed the radiosensitivity (dose ranging 0 to 10 Gy) under normoxia (20% O2) and moderate hypoxia (1% O2). Results. We observed that IDH1R132H U87 cells grow faster in hypoxia and were more sensitive to radiotherapy (in terms of cell mortality and colony formation assay) compared to nontransduced U87 and IDH1wt cells. This effect was not observed in normoxia. Conclusion. These data suggest that IDH1R132H mutation increases radiosensitivity in mild hypoxic conditions. PMID:24895549

  3. IDH1R132H Mutation Increases U87 Glioma Cell Sensitivity to Radiation Therapy in Hypoxia

    Directory of Open Access Journals (Sweden)

    Xiao-Wei Wang

    2014-01-01

    Full Text Available Objective. IDH1 codon 132 mutation (mostly Arg132His is frequently found in gliomas and is associated with longer survival. However, it is still unclear whether IDH1 mutation renders the cell more vulnerable to current treatment, radio- and chemotherapy. Materials and Methods. We transduced U87 with wild type IDH1 or IDH1R132H expressing lentivirus and analyzed the radiosensitivity (dose ranging 0 to 10 Gy under normoxia (20% O2 and moderate hypoxia (1% O2. Results. We observed that IDH1R132H U87 cells grow faster in hypoxia and were more sensitive to radiotherapy (in terms of cell mortality and colony formation assay compared to nontransduced U87 and IDH1wt cells. This effect was not observed in normoxia. Conclusion. These data suggest that IDH1R132H mutation increases radiosensitivity in mild hypoxic conditions.

  4. Y-27632 Increases Sensitivity of PANC-1 Cells to Epigallocatechin Gallate (EGCG) in Regulating Cell Proliferation and Migration

    Science.gov (United States)

    Liu, Xing; Bi, Yongyi

    2016-01-01

    Background The study aimed to investigate the inhibitory effect of (1R,4r)-4-((R)-1-aminoethyl)-N-(pyridin-4-yl) cyclohexanecarboxamide (Y-27632) and (−)-epigallocatechin-3-gallate (EGCG) on the proliferation and migration of PANC-1 cells. EGCG, found in green tea, has been previously shown to be one of the most abundant and powerful catechins in cancer prevention and treatment. Y-27632, a selective inhibitor of rho-associated protein kinase 1, is widely used in treating cardiovascular disease, inflammation, and cancer. Material/Methods PANC-1 cells, maintained in Dulbecco’s Modified Eagle’s Medium, were treated with dimethyl sulfoxide (control) as well as different concentrations (20, 40, 60, and 80 μg/mL) of EGCG for 48 h. In addition, PANC-1 cells were treated separately with 60 μg/mL EGCG, 20 μM Y-27632, and EGCG combined with Y-27632 (60 μg/mL EGCG + 20 μM Y-27632) for 48 h. The effect of EGCG and Y-27632 on the proliferation and migration of PANC-1 cells was evaluated using Cell Counting Kit-8 and transwell migration assays. The expression of peroxisome proliferator–activated receptor alpha (PPARα) and Caspase-3 mRNA was determined by Quantitative real-time polymerase chain reaction (RT-qPCR). Results EGCG (20–80 μg/mL) inhibited cell viability in a dose-dependent manner. Y-27632 enhanced the sensitivity of PANC-1 cells to EGCG (by increasing the expression of PPARα and Caspase-3 mRNA) and suppressed cell proliferation. PANC-1 cell migration was inhibited by treatment with a combination of EGCG and Y-27632. Conclusions Y-27632 increases the sensitivity of PANC-1 cells to EGCG in regulating cell proliferation and migration, which is likely to be related to the expression of PPARα mRNA and Caspase-3 mRNA. PMID:27694793

  5. Advancement of atmospheric-vacuum interfaces for mass spectrometers with a focus on increasing gas throughput for improving sensitivity.

    Science.gov (United States)

    Prasad, Satendra; Wouters, Eloy R; Dunyach, Jean-Jacques

    2015-08-18

    Ion sampling from an electrospray ionization (ESI) source was improved by increasing gas conductance of the MS inlet by 4.3-fold. Converting the gas throughput (Q) into sensitivity improvement was dependent on ion desolvation and handling of the gas load. Desolvation was addressed by using a novel slot shaped inlet that exhibited desolvation properties identical to the 0.58 mm i.d capillary. An assay tailored for "small molecules" at high chromatographic flow rate (500 μL/min) yielded a compound dependent 6.5 to 14-fold signal gain while analysis at nano chromatographic flow rate (300 nL/min) showed 2 to 3.5-fold improvement for doubly charged peptides. Improvement exceeding the Q (4.3-fold) at high chromatographic flow rate was explained by superior sampling of the spatially dispersed ion spray when using the slot shaped capillary. Sensitivity improvement across a wide range of chromatographic flow rate confirmed no compromise in ion desolvation with the increase in Q. Another improvement included less overflow of gas into the mass analyzer from the foreline region owing to the slot shape of the capillary. By doubling the roughing pump capacity and operating the electrodynamic ion funnel (EDIF) at ∼4 Torr, a single pumping stage was sufficient to handle the gas load. The transport of solvent clusters from the LC effluent into the mass analyzer was prevented by a "wavy shaped" transfer quadrupole and was compared with a benchmark approach that delivered ions orthogonally into a differentially pumped dual EDIF at comparable gas Q.

  6. Afatinib increases sensitivity to radiation in non-small cell lung cancer cells with acquired EGFR T790M mutation.

    Science.gov (United States)

    Zhang, Shirong; Zheng, Xiaoliang; Huang, Haixiu; Wu, Kan; Wang, Bing; Chen, Xufeng; Ma, Shenglin

    2015-03-20

    Afatinib is a second-generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and has shown a significant clinical benefit in non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations. However, the potential therapeutic effects of afatinib combining with other modalities, including ionizing radiation (IR), are not well understood. In this study, we developed a gefitinib-resistant cell subline (PC-9-GR) with a secondary EGFR mutation (T790M) from NSCLC PC-9 cells after chronic exposures to increasing doses of gefitinib. The presence of afatinib significantly increases the cell killing effect of radiation in PC-9-GR cells harboring acquired T790M, but not in H1975 cells with de novo T790M or in H460 cells that express wild-type EGFR. In PC-9-GR cells, afatinib remarkable blocks baseline of EGFR and ERK phosphorylations, and causes delay of IR-induced AKT phosphorylation. Afatinib treatment also leads to increased apoptosis and suppressed DNA damage repair in irradiated PC-9-GR cells, and enhanced tumor growth inhibition when combined with IR in PC-9-GR xenografts. Our findings suggest a potential therapeutic impact of afatinib as a radiation sensitizer in lung cancer cells harboring acquired T790M mutation, providing a rationale for a clinical trial with combination of afatinib and radiation in NSCLCs with EGFR T790M mutation.

  7. Deletion of the Wolfram syndrome-related gene Wfs1 results in increased sensitivity to ethanol in female mice.

    Science.gov (United States)

    Raud, Sirli; Reimets, Riin; Loomets, Maarja; Sütt, Silva; Altpere, Alina; Visnapuu, Tanel; Innos, Jürgen; Luuk, Hendrik; Plaas, Mario; Volke, Vallo; Vasar, Eero

    2015-08-01

    Wolfram syndrome, induced by mutation in WFS1 gene, increases risk of developing mood disorders in humans. In mice, Wfs1 deficiency cause higher anxiety-like behaviour and increased response to anxiolytic-like effect of diazepam, a GABAA receptor agonist. As GABAergic system is also target for ethanol, we analysed its anxiolytic-like and sedative properties in Wfs1-deficient mice using elevated plus-maze test and tests measuring locomotor activity and coordination, respectively. Additionally loss of righting reflex test was conducted to study sedative/hypnotic properties of ethanol, ketamine and pentobarbital. To evaluate pharmacokinetics of ethanol in mice enzymatic colour test was used. Finally, gene expression of alpha subunits of GABAA receptors following ethanol treatment was studied by real-time-PCR. Compared to wild-types, Wfs1-deficient mice were more sensitive to ethanol-induced anxiolytic-like effect, but less responsive to impairment of motor coordination. Ethanol and pentobarbital, but not ketamine, caused longer duration of hypnosis in Wfs1-deficient mice. The expression of Gabra2 subunit at 30 minutes after ethanol injection was significantly increased in the frontal cortex of Wfs1-deficient mice as compared to respective vehicle-treated mice. For the temporal lobe, similar change in Gabra2 mRNA occurred at 60 minutes after ethanol treatment in Wfs1-deficient mice. No changes were detected in Gabra1 and Gabra3 mRNA following ethanol treatment. Taken together, increased anxiolytic-like effect of ethanol in Wfs1-deficient mice is probably related to altered Gabra2 gene expression. Increased anti-anxiety effect of GABAA receptor agonists in the present work and earlier studies (Luuk et al., 2009) further suggests importance of Wfs1 gene in the regulation of emotional behaviour.

  8. Direct effects of TNF-α on local fuel metabolism and cytokine levels in the placebo-controlled, bilaterally infused human leg: increased insulin sensitivity, increased net protein breakdown, and increased IL-6 release.

    Science.gov (United States)

    Bach, Ermina; Nielsen, Roni R; Vendelbo, Mikkel H; Møller, Andreas B; Jessen, Niels; Buhl, Mads; K-Hafstrøm, Thomas; Holm, Lars; Pedersen, Steen B; Pilegaard, Henriette; Biensø, Rasmus S; Jørgensen, Jens O L; Møller, Niels

    2013-12-01

    Tumor necrosis factor-α (TNF-α) has widespread metabolic actions. Systemic TNF-α administration, however, generates a complex hormonal and metabolic response. Our study was designed to test whether regional, placebo-controlled TNF-α infusion directly affects insulin resistance and protein breakdown. We studied eight healthy volunteers once with bilateral femoral vein and artery catheters during a 3-h basal period and a 3-h hyperinsulinemic-euglycemic clamp. One artery was perfused with saline and one with TNF-α. During the clamp, TNF-α perfusion increased glucose arteriovenous differences (0.91 ± 0.17 vs. 0.74 ± 0.15 mmol/L, P = 0.012) and leg glucose uptake rates. Net phenylalanine release was increased by TNF-α perfusion with concomitant increases in appearance and disappearance rates. Free fatty acid kinetics was not affected by TNF-α, whereas interleukin-6 (IL-6) release increased. Insulin and protein signaling in muscle biopsies was not affected by TNF-α. TNF-α directly increased net muscle protein loss, which may contribute to cachexia and general protein loss during severe illness. The finding of increased insulin sensitivity, which could relate to IL-6, is of major clinical interest and may concurrently act to provide adequate tissue fuel supply and contribute to the occurrence of systemic hypoglycemia. This distinct metabolic feature places TNF-α among the rare insulin mimetics of human origin.

  9. Sensitivity of interglacial Greenland temperature and δ18O: ice core data, orbital and increased CO2 climate simulations

    Directory of Open Access Journals (Sweden)

    D. Swingedouw

    2011-09-01

    Full Text Available The sensitivity of interglacial Greenland temperature to orbital and CO2 forcing is investigated using the NorthGRIP ice core data and coupled ocean-atmosphere IPSL-CM4 model simulations. These simulations were conducted in response to different interglacial orbital configurations, and to increased CO2 concentrations. These different forcings cause very distinct simulated seasonal and latitudinal temperature and water cycle changes, limiting the analogies between the last interglacial and future climate. However, the IPSL-CM4 model shows similar magnitudes of Arctic summer warming and climate feedbacks in response to 2 × CO2 and orbital forcing of the last interglacial period (126 000 years ago. The IPSL-CM4 model produces a remarkably linear relationship between TOA incoming summer solar radiation and simulated changes in summer and annual mean central Greenland temperature. This contrasts with the stable isotope record from the Greenland ice cores, showing a multi-millennial lagged response to summer insolation. During the early part of interglacials, the observed lags may be explained by ice sheet-ocean feedbacks linked with changes in ice sheet elevation and the impact of meltwater on ocean circulation, as investigated with sensitivity studies. A quantitative comparison between ice core data and climate simulations requires stability of the stable isotope – temperature relationship to be explored. Atmospheric simulations including water stable isotopes have been conducted with the LMDZiso model under different boundary conditions. This set of simulations allows calculation of a temporal Greenland isotope-temperature slope (0.3–0.4‰ per °C during warmer-than-present Arctic climates, in response to increased CO2, increased ocean temperature and orbital forcing. This temporal slope appears half as large as the modern spatial gradient and is consistent with other ice core estimates. It may, however, be model-dependent, as indicated by

  10. Mouth breathing increases the pentylenetetrazole-induced seizure threshold in mice: a role for ATP-sensitive potassium channels.

    Science.gov (United States)

    Niaki, Seyed Esfandiar Akhavan; Shafaroodi, Hamed; Ghasemi, Mehdi; Shakiba, Bijan; Fakhimi, Ali; Dehpour, Ahamd Reza

    2008-08-01

    Nasal obstruction and consequent mouth breathing have been shown to change the acid-base balance, producing respiratory acidosis. Additionally, there exists a large body of evidence maintaining that acidosis affects the activity of ATP-sensitive potassium (K(ATP)) channels, which play a crucial role in the function of the central nervous system (CNS), for example, in modulating seizure threshold. Thus, in the study described here, we examined whether mouth breathing, induced by surgical ligation of nostrils, could affect the seizure threshold induced by pentylenetetrazole in male NMRI mice. Using the selective K(ATP) channel opener (diazoxide) and blocker (glibenclamide), we also evaluated the possible role of K(ATP) channels in this process. Our data revealed that seizure threshold was increased 6 to 72 hours after nasal obstruction, reaching a peak 48 hours afterward, compared with either control or sham-operated mice (Pmouth breathing, which could result in respiratory acidosis, increases seizure threshold in mice and K(ATP) channels may play a role in this effect.

  11. Increased sensitivity in PCR detection of tdh-positive Vibrio parahaemolyticus in seafood with purified template DNA.

    Science.gov (United States)

    Hara-Kudo, Y; Kasuga, Y; Kiuchi, A; Horisaka, T; Kawasumi, T; Kumagai, S

    2003-09-01

    PCR is an important method for the detection of thermostable direct hemolysin gene (tdh)-positive (pathogenic hemolysin-producing) strains of Vibrio parahaemolyticus in seafood because tdh-negative (nonpathogenic) V. parahaemolyticus strains often contaminate seafood and interfere with the direct isolation of tdh-positive V. parahaemolyticus. In this study, the use of PCR to detect the tdh gene of V. parahaemolyticus in various seafoods artificially contaminated with tdh-positive V. parahaemolyticus was examined. PCR was inhibited by substances in oysters, squid, mackerel, and yellowtail but not by cod, sea bream, scallop, short-necked clam, and shrimp. To improve detection, DNA was purified by either the silica membrane method, the glass fiber method, or the magnetic separation method, and the purified DNA was used as the PCR primer template. For all samples, the use of the silica membrane method and the glass fiber method increased detection sensitivity. The results of this study demonstrate that the use of properly purified template DNA for PCR markedly increases the effectiveness of the method in detecting pathogenic tdh-positive V. parahaemolyticus in contaminated seafood.

  12. Gabapentin potentiates sensitivity to the interoceptive effects of alcohol and increases alcohol self-administration in rats.

    Science.gov (United States)

    Besheer, Joyce; Frisbee, Suzanne; Randall, Patrick A; Jaramillo, Anel A; Masciello, Maria

    2016-02-01

    Gabapentin, a drug used in the treatment of epileptic seizures and neuropathic pain, has shown efficacy in the treatment of alcohol dependence. Moreover, given that gabapentin is used in the general population (e.g., non-dependent individuals, social drinkers), we sought to utilize preclinical assessments to examine the effects of gabapentin on sensitivity to moderate alcohol doses and alcohol self-administration in rats with a history of moderate drinking. To this end, we assessed whether gabapentin (0, 10, 30, 120 mg/kg, IG) pretreatment alters sensitivity to experimenter- and self-administered alcohol, and whether gabapentin alone has alcohol-like discriminative stimulus effects in rats trained to discriminate alcohol dose (1 g/kg, IG) vs. water. Second, we assessed whether gabapentin (0, 10, 30, 60 mg/kg, IG) would alter alcohol self-administration. Gabapentin pretreatment potentiated the interoceptive effects of both experimenter-administered and self-administered alcohol in discrimination-trained rats. Additionally, the highest gabapentin doses tested (30 and 120 mg/kg) were found to have partial alcohol-like discriminative stimulus effects when administered alone (e.g., without alcohol). In the self-administration trained rats, gabapentin pretreatment (60 mg/kg) resulted in an escalation in alcohol self-administration. Given the importance of interoceptive drug cues in priming and maintaining self-administration, these data define a specific behavioral mechanism (i.e., potentiation of alcohol effects) by which gabapentin may increase alcohol self-administration in non-dependent populations.

  13. Climate sensitivity due to increased CO2: experiments with a coupled atmosphere and ocean general circulation model

    Science.gov (United States)

    Washington, Warren M.; Meehl, Gerald A.

    1989-06-01

    A version of the National Center for Atmospheric Research community climate model — a global, spectral (R15) general circulation model — is coupled to a coarse-grid (5° latitude-] longitude, four-layer) ocean general circulation model to study the response of the climate system to increases of atmospheric carbon dioxide (CO2). Three simulations are run: one with an instantaneous doubling of atmospheric CO2 (from 330 to 660 ppm), another with the CO2 concentration starting at 330 ppm and increasing linearly at a rate of 1% per year, and a third with CO2 held constant at 330 pm. Results at the end of 30 years of simulation indicate a globally averaged surface air temperature increase of 1.6° C for the instantaneous doubling case and 0.7°C for the transient forcing case. Inherent characteristics of the coarse-grid ocean model flow sea-surface temperatures (SSTs) in the tropics and higher-than-observed SSTs and reduced sea-ice extent at higher latitudes] produce lower sensitivity in this model after 30 years than in earlier simulations with the same atmosphere coupled to a 50-m, slab-ocean mixed layer. Within the limitations of the simulated meridional overturning, the thermohaline circulation weakens in the coupled model with doubled CO2 as the high-latitude ocean-surface layer warms and freshens and westerly wind stress is decreased. In the transient forcing case with slowly increasing CO2 (30% increase after 30 years), the zonal mean warming of the ocean is most evident in the surface layer near 30° 50° S. Geographical plots of surface air temperature change in the transient case show patterns of regional climate anomalies that differ from those in the instantaneous CO2 doubling case, particularly in the North Atlantic and northern European regions. This suggests that differences in CO2 forcing in the climate system are important in CO2 response in regard to time-dependent climate anomaly regimes. This confirms earlier studies with simple climate models

  14. Knockdown of lecithin retinol acyltransferase increases all-trans retinoic acid levels and restores retinoid sensitivity in malignant melanoma cells.

    Science.gov (United States)

    Amann, Philipp M; Czaja, Katharina; Bazhin, Alexandr V; Rühl, Ralph; Skazik, Claudia; Heise, Ruth; Marquardt, Yvonne; Eichmüller, Stefan B; Merk, Hans F; Baron, Jens M

    2014-11-01

    Retinoids such as all-trans retinoic acid (ATRA) influence cell growth, differentiation and apoptosis and may play decisive roles in tumor development and progression. An essential retinoid-metabolizing enzyme known as lecithin retinol acyltransferase (LRAT) is expressed in melanoma cells but not in melanocytes catalysing the esterification of all-trans retinol (ATRol). In this study, we show that a stable LRAT knockdown (KD) in the human melanoma cell line SkMel23 leads to significantly increased levels of the substrate ATRol and biologically active ATRA. LRAT KD restored cellular sensitivity to retinoids analysed in cell culture assays and melanoma 3D skin models. Furthermore, ATRA-induced gene regulatory mechanisms drive depletion of added ATRol in LRAT KD cells. PCR analysis revealed a significant upregulation of retinoid-regulated genes such as CYP26A1 and STRA6 in LRAT KD cells, suggesting their possible involvement in mediating retinoid resistance in melanoma cells. In conclusion, LRAT seems to be important for melanoma progression. We propose that reduction in ATRol levels in melanoma cells by LRAT leads to a disturbance in cellular retinoid level. Balanced LRAT expression and activity may provide protection against melanoma development and progression. Pharmacological inhibition of LRAT activity could be a promising strategy for overcoming retinoid insensitivity in human melanoma cells.

  15. Increased N-Ethylmaleimide-Sensitive Factor Expression in Amygdala and Perirhinal Cortex during Habituation of Taste Neophobia

    Science.gov (United States)

    Gómez-Chacón, Beatriz; Gámiz, Fernando; Foster, Thomas C.

    2016-01-01

    Interactions between GluR2 and N-ethylmaleimide-sensitive factor (NSF) mediate AMPA receptors trafficking. This might be linked with molecular mechanisms related with memory formation. Previous research has shown basolateral amygdala (BLA) dependent activity changes in the perirhinal cortex (PRh) during the formation of taste memory. In the present experiments we investigate both the behavioral performance and the expression profile of NSF and GluR2 genes in several brain areas, including PRh, BLA, and hippocampus. Twenty-one naïve male Wistar rats were exposed to a saccharin solution (0.4%) during the first (novel), the second (Familiar I), and the sixth presentation (Familiar II). Total RNA was extracted and gene expression was measured by quantitative PCR (qPCR) using TaqMan gene expression assays. In addition the expression of the synaptic plasticity related immediate early genes, Homer 1 and Narp, was also assessed. We have found increased expression of NSF gene in BLA and PRh in Group Familiar I in comparison with Familiar II. No changes in the expression of GluR2, Homer 1, and Narp genes were found. The results suggest the relevance of a potential network in the temporal lobe for taste recognition memory and open new possibilities for understanding the molecular mechanisms mediating the impact of sensory experience on brain circuit function. PMID:26839712

  16. Using polarization-sensitive optical coherence tomography to identify tumor stromal fibrosis and increase tumor biopsy yield (Conference Presentation)

    Science.gov (United States)

    Hariri, Lida P.; Adams, David C.; Miller, Alyssa J.; Mino-Kenudson, Mari; Suter, Melissa J.

    2016-03-01

    Tissue biopsy is the principal method used to diagnose tumors in a variety of organ systems. It is essential to maximize tumor yield in biopsy specimens for both clinical diagnostic and research purposes. This is particularly important in tumors where additional tissue is needed for molecular analysis to identify patients who would benefit from mutation-specific targeted therapy, such as in lung carcinomas. Inadvertent sampling of fibrotic stroma within tumor nodules contaminates biopsies, decreases tumor yield, and can impede diagnosis. The ability to assess tumor composition and guide biopsy site selection in real time is likely to improve diagnostic yield. Polarization sensitive OCT (PS-OCT) measures birefringence in organized tissues, such as collagen, and could be used to distinguish tumor from fibrosis. In this study, PS-OCT was obtained in 65 lung nodule samples from surgical resection specimens containing varying ratios of tumor and fibrosis. PS-OCT was obtained with either a custom-built helical scanning catheter (0.8 or 1.6mm in diameter) or a dual-axis bench top scanner. Strong birefringence was observed in nodules containing dense fibrosis, with no birefringence in adjacent regions of tumor. Tumors admixed with early, loosely-organized collagen demonstrated mild-to-moderate birefringence, and tumors with little collagen content showed little to no birefringent signal. PS-OCT provides significant insights into tumor nodule composition, and has potential to differentiate tumor from stromal fibrosis during biopsy site selection to increase diagnostic tumor yield.

  17. Increased N-Ethylmaleimide-Sensitive Factor Expression in Amygdala and Perirhinal Cortex during Habituation of Taste Neophobia

    Directory of Open Access Journals (Sweden)

    Beatriz Gómez-Chacón

    2016-01-01

    Full Text Available Interactions between GluR2 and N-ethylmaleimide-sensitive factor (NSF mediate AMPA receptors trafficking. This might be linked with molecular mechanisms related with memory formation. Previous research has shown basolateral amygdala (BLA dependent activity changes in the perirhinal cortex (PRh during the formation of taste memory. In the present experiments we investigate both the behavioral performance and the expression profile of NSF and GluR2 genes in several brain areas, including PRh, BLA, and hippocampus. Twenty-one naïve male Wistar rats were exposed to a saccharin solution (0.4% during the first (novel, the second (Familiar I, and the sixth presentation (Familiar II. Total RNA was extracted and gene expression was measured by quantitative PCR (qPCR using TaqMan gene expression assays. In addition the expression of the synaptic plasticity related immediate early genes, Homer 1 and Narp, was also assessed. We have found increased expression of NSF gene in BLA and PRh in Group Familiar I in comparison with Familiar II. No changes in the expression of GluR2, Homer 1, and Narp genes were found. The results suggest the relevance of a potential network in the temporal lobe for taste recognition memory and open new possibilities for understanding the molecular mechanisms mediating the impact of sensory experience on brain circuit function.

  18. Increased N-Ethylmaleimide-Sensitive Factor Expression in Amygdala and Perirhinal Cortex during Habituation of Taste Neophobia.

    Science.gov (United States)

    Gómez-Chacón, Beatriz; Gámiz, Fernando; Foster, Thomas C; Gallo, Milagros

    2016-01-01

    Interactions between GluR2 and N-ethylmaleimide-sensitive factor (NSF) mediate AMPA receptors trafficking. This might be linked with molecular mechanisms related with memory formation. Previous research has shown basolateral amygdala (BLA) dependent activity changes in the perirhinal cortex (PRh) during the formation of taste memory. In the present experiments we investigate both the behavioral performance and the expression profile of NSF and GluR2 genes in several brain areas, including PRh, BLA, and hippocampus. Twenty-one naïve male Wistar rats were exposed to a saccharin solution (0.4%) during the first (novel), the second (Familiar I), and the sixth presentation (Familiar II). Total RNA was extracted and gene expression was measured by quantitative PCR (qPCR) using TaqMan gene expression assays. In addition the expression of the synaptic plasticity related immediate early genes, Homer 1 and Narp, was also assessed. We have found increased expression of NSF gene in BLA and PRh in Group Familiar I in comparison with Familiar II. No changes in the expression of GluR2, Homer 1, and Narp genes were found. The results suggest the relevance of a potential network in the temporal lobe for taste recognition memory and open new possibilities for understanding the molecular mechanisms mediating the impact of sensory experience on brain circuit function.

  19. Sensitivity to Spacing Information Increases More for the Eye Region than for the Mouth Region during Childhood

    Science.gov (United States)

    de Heering, Adelaide; Schiltz, Christine

    2013-01-01

    Sensitivity to spacing information within faces improves with age and reaches maturity only at adolescence. In this study, we tested 6-16-year-old children's sensitivity to vertical spacing when the eyes or the mouth is the facial feature selectively manipulated. Despite the similar discriminability of these manipulations when they are embedded in…

  20. Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.

    Science.gov (United States)

    Banerjee, Atrayee; Abdelmegeed, Mohamed A; Jang, Sehwan; Song, Byoung-Joon

    2015-01-01

    The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT) or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH) (3.5 g/kg/dose oral gavages at 12-h intervals) or dextrose (Control). Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4), leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1) were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART), are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

  1. Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.

    Directory of Open Access Journals (Sweden)

    Atrayee Banerjee

    Full Text Available The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH (3.5 g/kg/dose oral gavages at 12-h intervals or dextrose (Control. Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4, leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1 were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART, are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

  2. Increased amphetamine-induced locomotor activity, sensitization, and accumbal dopamine release in M5 muscarinic receptor knockout mice

    DEFF Research Database (Denmark)

    Schmidt, Lene S; Miller, Anthony D; Lester, Deranda B

    2010-01-01

    showed that M(5) receptor knockout (M (5) (-/-) ) mice are less sensitive to the reinforcing properties of addictive drugs. MATERIALS AND METHODS: Here, we investigate the role of M(5) receptors in the effects of amphetamine and cocaine on locomotor activity, locomotor sensitization, and dopamine release...... and locomotor sensitization were enhanced in M (5) (-/-) mice, while the effects of cocaine were similar in M (5) (-/-) and wild-type mice. RESULTS: Consistent with the behavioral results, amphetamine-, but not cocaine, -elicited dopamine release in nucleus accumbens was enhanced in M (5) (-/-) mice. DISCUSSION......: The different effects of amphetamine and cocaine in M (5) (-/-) mice may be due to the divergent pharmacological profile of the two drugs, where amphetamine, but not cocaine, is able to release intracellular stores of dopamine. In conclusion, we show here for the first time that amphetamine...

  3. Acyl CoA synthetase 5 (ACSL5 ablation in mice increases energy expenditure and insulin sensitivity and delays fat absorption

    Directory of Open Access Journals (Sweden)

    Thomas A. Bowman

    2016-03-01

    Conclusions: In summary, ACSL5−/− mice have increased hepatic and serum FGF21 levels, reduced adiposity, improved insulin sensitivity, increased energy expenditure and delayed triglyceride absorption. These studies suggest that ACSL5 is an important regulator of whole-body energy metabolism and ablation of ACSL5 may antagonize the development of obesity and insulin resistance.

  4. Estratégias para aumento de sensibilidade em espectrofotometria UV-VIS Strategies to increase sensitivity in UV-VIS spectrophotometry

    Directory of Open Access Journals (Sweden)

    Fábio R. P. Rocha

    2004-10-01

    Full Text Available Spectrophotometry is one of the most widespread analytical techniques due to its simplicity, reliability, and low-cost instrumentation for both direct measurements and coupled to other techniques or processes such as chromatography, electrophoresis and flow analysis. However, the application is often limited by sensitivity. This article describes some advances that greatly improve the performance of spectrophotometric measurements, especially in order to increase sensitivity, including the employment of liquid-core waveguides and solid-phase spectrophotometry.

  5. Phosphorylation of hormone-sensitive lipase by protein kinase A in vitro promotes an increase in its hydrophobic surface area

    DEFF Research Database (Denmark)

    Krintel, Christian; Mörgelin, Matthias; Logan, Derek T;

    2009-01-01

    Hormone-sensitive lipase (EC 3.1.1.79; HSL) is a key enzyme in the mobilization of fatty acids from stored triacylglycerols. HSL activity is controlled by phosphorylation of at least four serines. In rat HSL, Ser563, Ser659 and Ser660 are phosphorylated by protein kinase A (PKA) in vitro as well...

  6. DISRUPTION OF THE SACCHAROMYCES CEREVISIAE GENE FOR NADPH-CYTOCHROME P450-REDUCTASE CAUSES INCREASED SENSITIVITY TO KETOCONAZOLE

    Science.gov (United States)

    Strains of Saccharomyces cerevisiae deleted in the NADPH-cytochrome P450 reductase gene by transplacement are 200-fold more sensitive to ketoconazole, an inhibitor of the cytochrome P450 lanosterol 14-demethylase. Resistance is restored through complementation by the plasmid-born...

  7. A polymorphism in the glucocorticoid receptor gene may be associated with an increased sensitivity to glucocorticoids in vivo

    NARCIS (Netherlands)

    Huizenga, NATM; Koper, JW; De Lange, P; Pols, HAP; Stolk, RP; Burger, H; Grobbee, DE; Brinkmann, AO; De Jong, FH; Lamberts, SWJ

    1998-01-01

    We investigated whether a polymorphism at nucleotide position 1220, resulting in an asparagine-to-serine change at codon 363 in the glucocorticoid receptor (GR) gene is associated with an altered sensitivity to glucocorticoids. In a group of 216 elderly persons, 13 heterozygotes for the N363S polymo

  8. Replacing Fish Oil with Vegetable Oils in Salmon Feed Increases Hepatic Lipid Accumulation and Reduces Insulin Sensitivity in Mice

    DEFF Research Database (Denmark)

    Midtbø, Lisa Kolden

    %) of FO with different vegetable oils (VOs); rape seed oil (WDRO), olive oil (WD-OO) or soybean oil (WD-SO). These diets were given to C57BL/6J mice, and mice had higher hepatic lipid accumulation and lower insulin sensitivity when given WD-SO compared with WD-FO. Mice given WD-SO had higher hepatic...

  9. Increasing the sensitivity of NMR diffusion measurements by paramagnetic longitudinal relaxation enhancement, with application to ribosome–nascent chain complexes

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Sammy H. S.; Waudby, Christopher A.; Cassaignau, Anaïs M. E.; Cabrita, Lisa D.; Christodoulou, John, E-mail: j.christodoulou@ucl.ac.uk [University College London and Birkbeck College, Institute of Structural and Molecular Biology (United Kingdom)

    2015-10-15

    The translational diffusion of macromolecules can be examined non-invasively by stimulated echo (STE) NMR experiments to accurately determine their molecular sizes. These measurements can be important probes of intermolecular interactions and protein folding and unfolding, and are crucial in monitoring the integrity of large macromolecular assemblies such as ribosome–nascent chain complexes (RNCs). However, NMR studies of these complexes can be severely constrained by their slow tumbling, low solubility (with maximum concentrations of up to 10 μM), and short lifetimes resulting in weak signal, and therefore continuing improvements in experimental sensitivity are essential. Here we explore the use of the paramagnetic longitudinal relaxation enhancement (PLRE) agent NiDO2A on the sensitivity of {sup 15}N XSTE and SORDID heteronuclear STE experiments, which can be used to monitor the integrity of these unstable complexes. We exploit the dependence of the PLRE effect on the gyromagnetic ratio and electronic relaxation time to accelerate recovery of {sup 1}H magnetization without adversely affecting storage on N{sub z} during diffusion delays or introducing significant transverse relaxation line broadening. By applying the longitudinal relaxation-optimized SORDID pulse sequence together with NiDO2A to 70S Escherichia coli ribosomes and RNCs, NMR diffusion sensitivity enhancements of up to 4.5-fold relative to XSTE are achieved, alongside ∼1.9-fold improvements in two-dimensional NMR sensitivity, without compromising the sample integrity. We anticipate these results will significantly advance the use of NMR to probe dynamic regions of ribosomes and other large, unstable macromolecular assemblies.Graphical Abstract.

  10. Jicama (Pachyrhizus erosus) extract increases insulin sensitivity and regulates hepatic glucose in C57BL/Ksj-db/db mice

    OpenAIRE

    Park, Chan Joo; Lee, Hyun-Ah; Han, Ji-Sook

    2015-01-01

    This study investigated the effect of jicama extract on hyperglycemia and insulin sensitivity in an animal model of type 2 diabetes. Male C57BL/Ksj-db/db mice were divided into groups subsequently fed a regular diet (controls), or diet supplemented with jicama extract, and rosiglitazone. After 6 weeks, blood levels of glucose and glycosylated hemoglobin were significantly lower in animals administered the jicama extract than the control group. Additionally, glucose and insulin tolerance tests...

  11. Point-Of-Care p24 Infant Testing for HIV May Increase Patient Identification despite Low Sensitivity

    Science.gov (United States)

    Bollinger, Timothy; Mabunda, Nédio; Vubil, Adolfo; Tobaiwa, Ocean; Quevedo, Jorge I.; Loquiha, Osvaldo; Vojnov, Lara; Peter, Trevor F.; Jani, Ilesh V.

    2017-01-01

    The long delay in returning test results during early infant diagnosis of HIV (EID) often causes loss-to-follow-up prior to antiretroviral treatment (ART) initiation in resource-limited settings. A point-of-care (POC) test may help overcome these challenges. We evaluated the performance of the LYNX p24 Antigen POC test in Mozambique. 879 HIV-exposed infants under 18 months of age were enrolled consecutively at three primary healthcare clinics (PHC). Lancet heel-drawn blood was tested on-site by nurses using a prototype POC test for HIV Gag p24 antigen detection. Results of POC testing were compared to laboratory-based nucleic acid testing on dried blood spots. A comparison of the effect of sensitivity and timely test results return on successful diagnosis by POC and laboratory-based platforms was also calculated. The sensitivity and specificity of the LYNX p24 Ag test were 71.9%; (95% confidence interval [CI]: 58.5–83.0%) and 99.6% (95% CI: 98.9–99.9%), respectively. The predictive value of positive and negative tests were 93.2% (95% CI: 81.3–98.6%) and 97.9% (95% CI: 96.8–98.8%), respectively. Overall agreement was high (Cohen Kappa = 0.80; 95% CI: 0.71–0.89). Despite its lower sensitivity, the POC test had the potential to provide test results to up to 81% more patients compared to the laboratory-based test. This prototype POC p24 assay was feasible for use in PHCs but demonstrated low sensitivity for HIV detection. POC EID technologies that perform below standard recommendations may still be valuable diagnostic tools in settings with inefficient EID networks. PMID:28060886

  12. Deficiency of the Caenorhabditis elegans DNA polymerase eta homologue increases sensitivity to UV radiation during germ-line development.

    Science.gov (United States)

    Ohkumo, Tsuyoshi; Masutani, Chikahide; Eki, Toshihiko; Hanaoka, Fumio

    2006-01-01

    Defects in the human XPV/POLH gene result in the variant form of the disease xeroderma pigmentosum (XP-V). The gene encodes DNA polymerase eta (Poleta), which catalyzes translesion synthesis (TLS) past UV-induced cyclobutane pyrimidine dimers (CPDs) and other lesions. To further understand the roles of Poleta in multicellular organisms, we analyzed phenotypes caused by suppression of Caenorhabditis elegans POLH (Ce-POLH) by RNA interference (RNAi). F1 and F2 progeny from worms treated by Ce-POLH-specific RNAi grew normally, but F1 eggs laid by worms treated by RNAi against Ce-POLD, which encodes Poldelta did not hatch. These results suggest that Poldelta but not Poleta is essential for C. elegans embryogenesis. Poleta-targeted embryos UV-irradiated after egg laying were only moderately sensitive. In contrast, Poleta-targeted embryos UV-irradiated prior to egg laying exhibited severe sensitivity, indicating that Poleta contributes significantly to damage tolerance in C. elegans in early embryogenesis but only modestly at later stages. As early embryogenesis is characterized by high levels of DNA replication, Poleta may confer UV resistance in C. elegans, perhaps by catalyzing TLS in early embryogenesis.

  13. The increased endotoxin-sensitivity of pregnant rats, as reflected by glomerular Ecto-ADP-ase activity, is not dependent on the presence of decidual cells

    NARCIS (Netherlands)

    Faas, MM; Schuiling, GA; Baller, JFW; Valkhof, N; Bakker, WW

    1996-01-01

    In the present study the possible role of decidual cells in the pregnancy-associated increased sensitivity of glomerular ecto-ADP-ase to endotoxin was investigated. Early (day 5) pregnant (E-Pr; n = 10), pseudopregnant (E-PSP; n = 10), (day 5), pseudopregnant rats with a decidualized uterus (E-DEC;

  14. Early enhancements of hepatic and later of peripheral insulin sensitivity combined with increased postprandial insulin secretion contribute to improved glycemic control after Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Bojsen-Møller, Kirstine N; Dirksen, Carsten; Jørgensen, Nils Bruun;

    2014-01-01

    to an intravenous glucose-glucagon challenge as well as an oral glucose load. Already within 1 week, RYGB reduced basal glucose production, improved basal hepatic insulin sensitivity and increased insulin clearance highlighting the liver as an important organ responsible for the early effects on glucose metabolism...

  15. Protective effects of berberine on high fat-induced kidney damage by increasing serum adiponectin and promoting insulin sensitivity.

    Science.gov (United States)

    Wu, Ueyue; Cha, Ying; Huang, Xinmei; Liu, Jun; Chen, Zaoping; Wang, Fang; Xu, Jiong; Sheng, Li; Ding, Heyuan

    2015-01-01

    Berberine (BBR) has been reported in several studies in cell and animal models. However, the mechanism of actions is not fully understood. The present study was therefore aimed to explore the effects of berberine on insulin sensitivity and kidney damage in a high fat diet rat model. Impaired glucose tolerance rats induced by injection of berberine while fed with high fat laboratory chow. After rats were treated for 4 weeks, OGTT and IPITT were determined. Mass and PAS were used to study the kidney tissue. ELISA was used to detect the protein concentration of CRP and TNF-α. Western blot was used to detect the proteins adiponectin, adipoR1, adipoR2 and p-AMPK expression level. These encouraging findings suggest that berberine has excellent pharmacological potential to prevent kidney damage.

  16. Co-treatment with the anti-malarial drugs mefloquine and primaquine highly sensitizes drug-resistant cancer cells by increasing P-gp inhibition.

    Science.gov (United States)

    Kim, Ju-Hwa; Choi, Ae-Ran; Kim, Yong Kee; Yoon, Sungpil

    2013-11-22

    The purpose of this study was to identify conditions that will increase the sensitivity of resistant cancer cells to anti-mitotic drugs. Currently, atovaquine (ATO), chloroquine (CHL), primaquine (PRI), mefloquine (MEF), artesunate (ART), and doxycycline (DOY) are the most commonly used anti-malarial drugs. Herein, we tested whether anti-malarial drugs can sensitize drug-resistant KBV20C cancer cells. None of the six tested anti-malarial drugs was found to better sensitize the drug-resistant cells compared to the sensitive KB cells. With an exception of DOY, all other anti-malarial drugs tested could sensitize both KB and KBV20C cells to a similar extent, suggesting that anti-malarial drugs could be used for sensitive as well as resistant cancer cells. Furthermore, we examined the effects of anti-malarial drugs in combination with an antimitotic drug, vinblastine (VIN) on the sensitisation of resistant KBV20C cells. Using viability assay, microscopic observation, assessment of cleaved PARP, and Hoechst staining, we identified that two anti-malarial drugs, PRI and MEF, highly sensitized KBV20C-resistant cells to VIN treatment. Moreover, PRI- or MEF-induced sensitisation was not observed in VIN-treated sensitive KB parent cells, suggesting that the observed effect is specific to resistant cancer cells. We demonstrated that the PRI and MEF sensitisation mechanism mainly depends on the inhibition of p-glycoprotein (P-gp). Our findings may contribute to the development of anti-malarial drug-based combination therapies for patients resistant to anti-mitotic drugs.

  17. Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to increased cell proliferation and tumor risk

    Science.gov (United States)

    Kaneda, Atsushi; Wang, Chiaochun J.; Cheong, Raymond; Timp, Winston; Onyango, Patrick; Wen, Bo; Iacobuzio-Donahue, Christine A.; Ohlsson, Rolf; Andraos, Rita; Pearson, Mark A.; Sharov, Alexei A.; Longo, Dan L.; Ko, Minoru S. H.; Levchenko, Andre; Feinberg, Andrew P.

    2007-01-01

    Loss of imprinting (LOI) of the insulin-like growth factor-II gene (IGF2), leading to abnormal activation of the normally silent maternal allele, is a common human epigenetic population variant associated with a 5-fold increased frequency of colorectal neoplasia. Here, we show first that LOI leads specifically to increased expression of proliferation-related genes in mouse intestinal crypts. Surprisingly, LOI(+) mice also have enhanced sensitivity to IGF-II signaling, not simply increased IGF-II levels, because in vivo blockade with NVP-AEW541, a specific inhibitor of the IGF-II signaling receptor, showed reduction of proliferation-related gene expression to levels half that seen in LOI(−) mice. Signal transduction assays in microfluidic chips confirmed this enhanced sensitivity with marked augmentation of Akt/PKB signaling in LOI(+) cells at low doses of IGF-II, which was reduced in the presence of the inhibitor to levels below those found in LOI(−) cells, and was associated with increased expression of the IGF1 and insulin receptor genes. We exploited this increased IGF-II sensitivity to develop an in vivo chemopreventive strategy using the azoxymethane (AOM) mutagenesis model. LOI(+) mice treated with AOM showed a 60% increase in premalignant aberrant crypt foci (ACF) formation over LOI(−) mice. In vivo IGF-II blockade with NVP-AEW541 abrogated this effect, reducing ACF to a level 30% lower even than found in exposed LOI(−) mice. Thus, LOI increases cancer risk in a counterintuitive way, by increasing the sensitivity of the IGF-II signaling pathway itself, providing a previously undescribed epigenetic chemoprevention strategy in which cells with LOI are “IGF-II addicted” and undergo reduced tumorigenesis in the colon upon IGF-II pathway blockade. PMID:18087038

  18. Efficiency improvement of dye-sensitized tandem solar cell by increasing the photovoltage of the back sub-cell

    Energy Technology Data Exchange (ETDEWEB)

    Fan Shengqiang [Department of Advanced Materials Chemistry, Korea University, Jochiwon, Chungnam 339-700 (Korea, Republic of); Department of Applied Chemistry, School of Science, Xi' an Jiaotong University, Xi' an, Shaanxi 710049 (China); Fang Baizeng, E-mail: shengqiang_fan@sohu.co [Department of Advanced Materials Chemistry, Korea University, Jochiwon, Chungnam 339-700 (Korea, Republic of); Choi, Hyunbong; Paik, Sanghyun; Kim, Chulwoo; Jeong, Ban-Seok; Kim, Jeum-Jong [Department of Advanced Materials Chemistry, Korea University, Jochiwon, Chungnam 339-700 (Korea, Republic of); Ko, Jaejung, E-mail: jko@korea.ac.k [Department of Advanced Materials Chemistry, Korea University, Jochiwon, Chungnam 339-700 (Korea, Republic of)

    2010-06-01

    In tandem-structured dye-sensitized solar cell (DSSC) composed of two parallel-connected sub-cells, the photovoltage (V{sub oc}) generated by the back sub-cell is usually rather low, resulting in low V{sub oc} and conversion efficiency (eta) of the tandem cell. To solve this issue, two simple but very efficient strategies, namely, the filling of Li{sup +}-absent electrolyte and/or coating Al{sub 2}O{sub 3} on TiO{sub 2} electrode surface in the back sub-cell, were explored to enhance the V{sub oc} of the back sub-cell and hence that of the tandem cell. The former strategy was expected to heighten the energy level of TiO{sub 2} conduction band, and the latter one to retard the charge recombination. The photovoltaic performance measurements reveal that in the both cases, although there was a slight decrease in the photocurrent (J{sub sc}), an obvious rise in the V{sub oc} was achieved for the tandem cells, leading to significant improvements in eta of the tandem cells. Compared to the individual organic dye-sensitized solar cell (the highest eta is 7.58%), the tandem cell with two organic dyes having complementary absorption spectra demonstrates an improved efficiency of up to 8.33% by a combinational application of Li{sup +}-absent electrolyte and Al{sub 2}O{sub 3} overcoat. The results presented in this study highlight that the efficiency of a parallel-connected tandem-structured DSSC can be improved significantly through enhancing the photovoltage of the back sub-cell, which is first time reported.

  19. Decreased myo-inositol to chiro-inositol (M/C) ratios and increased M/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls.

    Science.gov (United States)

    Heimark, Douglas; McAllister, Jan; Larner, Joseph

    2014-01-01

    Previous studies from our and other labs have shown that insulin resistance is associated with an inositol imbalance of excess myo-inositol and deficient chiro-inositol together with a deficiency of myo-inositol to chiro-inositol epimerase in vivo and in vitro. In this report, we utilized well characterized theca cells from normal cycling women, with normal insulin sensitivity, and theca cells from women with polycystic ovary syndrome (PCOS), with increased insulin sensitivity to examine the myo-inositol to chiro-inisitol (M/C) ratio and the myo-inositol to chiro-inositol epimerase activity. PCOS theca cells with increased insulin sensitivity were specifically used to investigate whether the inositol imbalance and myo-inositol to chiro-inositol epimerase are regulated in a similar or the opposite direction than that observed in insulin resistant cells. The results of these studies are the first to demonstrate that in insulin sensitive PCOS theca cells the inositol imbalance goes in the opposite direction to that observed in insulin resistant cells, and there is a decreased M/C ratio and an increased myo-inositol to chiro-inositol epimerase activity. Further biochemical and genetic studies will probe the mechanisms involved.

  20. “It’s All We Got Left”. Why Poor Smokers are Less Sensitive to Cigarette Price Increases

    Directory of Open Access Journals (Sweden)

    Patrick Peretti-Watel

    2009-02-01

    Full Text Available In France, between 2000 and 2008, concurrently to the increase in cigarette price, we observed an increasing social differentiation of cigarette smoking: smoking prevalence decreased among executive managers and professional occupations, it remained stable among manual workers, and it increased among the unemployed. Poor smokers were heavier smokers, they were more frequently tobacco-dependent, and they were more prone to smoke automatically or to reduce “negative feelings”. In-depth interviews provided a more comprehensive insight into poor smokers’ motivations: they were aware of their addiction, but they also talked about the pleasure they get from smoking, and they highlighted the essential needs satisfied by smoking: stress relief, cheap leisure, compensation for loneliness, break-up or redundancy… Acknowledging the functional aspects of smoking experienced by poor smokers helps to understand why increasing the cigarette price is unlikely to deter many poor smokers from smoking.

  1. Men who have sex with men sensitivity training reduces homoprejudice and increases knowledge among Kenyan healthcare providers in coastal Kenya

    Directory of Open Access Journals (Sweden)

    Elise M van der Elst

    2013-12-01

    Full Text Available Introduction: Healthcare workers (HCWs in Africa typically receive little or no training in the healthcare needs of men who have sex with men (MSM, limiting the effectiveness and reach of population-based HIV control measures among this group. We assessed the effect of a web-based, self-directed sensitivity training on MSM for HCWs (www.marps-africa.org, combined with facilitated group discussions on knowledge and homophobic attitudes among HCWs in four districts of coastal Kenya. Methods: We trained four district “AIDS coordinators” to provide a two-day training to local HCWs working at antiretroviral therapy-providing facilities in coastal Kenya. Self-directed learning supported by group discussions focused on MSM sexual risk practices, HIV prevention and healthcare needs. Knowledge was assessed prior to training, immediately after training and three months after training. The Homophobia Scale assessed homophobic attitudes and was measured before and three months after training. Results: Seventy-four HCWs (68% female; 74% clinical officers or nurses; 84% working in government facilities from 49 health facilities were trained, of whom 71 (96% completed all measures. At baseline, few HCWs reported any prior training on MSM anal sexual practices, and most HCWs had limited knowledge of MSM sexual health needs. Homophobic attitudes were most pronounced among HCWs who were male, under 30 years of age, and working in clinical roles or government facilities. Three months after training, more HCWs had adequate knowledge compared to baseline (49% vs. 13%, McNemar's test p<0.001; this was most pronounced in those with clinical or administrative roles and in those from governmental health providers. Compared to baseline, homophobic attitudes had decreased significantly three months after training, particularly among HCWs with high homophobia scores at baseline, and there was some evidence of correlation between improvements in knowledge and reduction

  2. Sensitivity to isoflurane anesthesia increases in autism spectrum disorder Shank3(+/∆c) mutant mouse model.

    Science.gov (United States)

    Li, Changsheng; Schaefer, Michele; Gray, Christy; Yang, Ya; Furmanski, Orion; Liu, Sufang; Worley, Paul; Mintz, C David; Tao, Feng; Johns, Roger A

    Autism is a heterogeneous developmental disorder characterized by impaired social interaction, impaired communication skills, and restricted and repetitive behavior. The abnormal behaviors of these patients can make their anesthetic and perioperative management difficult. Evidence in the literature suggests that some patients with autism or specific autism spectrum disorders (ASD) exhibit altered responses to pain and to anesthesia or sedation. A genetic mouse model of one particular ASD, Phelan McDermid Syndrome, has been developed that has a Shank3 haplotype truncation (Shank3(+/Δc)). These mice exhibit important characteristics of autism that mimic human autistic behavior. Our study demonstrates that a Shank3(+/ΔC) mutation in mice is associated with a reduction in both the MAC and RREC50 of isoflurane and down regulation of NR1 in vestibular nuclei and PSD95 in spinal cord. Decreased expression of NR1 and PSD95 in the central nervous system of Shank3(+/ΔC) mice could help reduce the MAC and RREC50 of isoflurane, which would warrant confirmation in a clinical study. If Shank3 mutations are found to affect anesthetic sensitivity in patients with ASD, better communication and stricter monitoring of anesthetic depth may be necessary.

  3. Deficient expression of aldehyde dehydrogenase 1A1 is consistent with increased sensitivity of Gorlin syndrome patients to radiation carcinogenesis.

    Science.gov (United States)

    Wright, Aaron T; Magnaldo, Thierry; Sontag, Ryan L; Anderson, Lindsey N; Sadler, Natalie C; Piehowski, Paul D; Gache, Yannick; Weber, Thomas J

    2015-06-01

    Human phenotypes that are highly susceptible to radiation carcinogenesis have been identified. Sensitive phenotypes often display robust regulation of molecular features that modify biological response, which can facilitate identification of the pathways/networks that contribute to pathophysiological outcomes. Here we interrogate primary dermal fibroblasts isolated from Gorlin syndrome patients (GDFs), who display a pronounced inducible tumorigenic response to radiation, in comparison to normal human dermal fibroblasts (NHDFs). Our approach exploits newly developed thiol reactive probes to define changes in protein thiol profiles in live cell studies, which minimizes artifacts associated with cell lysis. Redox probes revealed deficient expression of an apparent 55 kDa protein thiol in GDFs from independent Gorlin syndrome patients, compared with NHDFs. Proteomics tentatively identified this protein as aldehyde dehydrogenase 1A1 (ALDH1A1), a key enzyme regulating retinoic acid synthesis, and ALDH1A1 protein deficiency in GDFs was confirmed by Western blot. A number of additional protein thiol differences in GDFs were identified, including radiation responsive annexin family members and lamin A/C. Collectively, candidates identified in our study have plausible implications for radiation health effects and cancer susceptibility.

  4. Chronic fluoxetine treatment increases NO bioavailability and calcium-sensitive potassium channels activation in rat mesenteric resistance arteries.

    Science.gov (United States)

    Pereira, Camila A; Ferreira, Nathanne S; Mestriner, Fabiola L; Antunes-Rodrigues, José; Evora, Paulo R B; Resstel, Leonardo B M; Carneiro, Fernando S; Tostes, Rita C

    2015-10-15

    Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has effects beyond its antidepressant properties, altering, e.g., mechanisms involved in blood pressure and vasomotor tone control. Although many studies have addressed the acute impact of fluoxetine on the cardiovascular system, there is a paucity of information on the chronic vascular effects of this SSRI. We tested the hypothesis that chronic fluoxetine treatment enhances the vascular reactivity to vasodilator stimuli by increasing nitric oxide (NO) signaling and activation of potassium (K+) channels. Wistar rats were divided into two groups: (I) vehicle (water for 21 days) or (II) chronic fluoxetine (10 mg/kg/day in the drinking water for 21 days). Fluoxetine treatment increased endothelium-dependent and independent vasorelaxation (analyzed by mesenteric resistance arteries reactivity) as well as constitutive NO synthase (NOS) activity, phosphorylation of eNOS at Serine1177 and NO production, determined by western blot and fluorescence. On the other hand, fluoxetine treatment did not alter vascular expression of neuronal and inducible NOS or guanylyl cyclase (GC). Arteries from fluoxetine-treated rats exhibited increased relaxation to pinacidil. Increased acetylcholine vasorelaxation was abolished by a calcium-activated K+ channel (KCa) blocker, but not by an inhibitor of KATP channels. On the other hand, vascular responses to Bay 41-2272 and 8-bromo-cGMP were similar between the groups. In conclusion, chronic fluoxetine treatment increases endothelium-dependent and independent relaxation of mesenteric resistance arteries by mechanisms that involve increased eNOS activity, NO generation, and KCa channels activation. These effects may contribute to the cardiovascular effects associated with chronic fluoxetine treatment.

  5. Free-swimming northern elephant seals have low field metabolic rates that are sensitive to an increased cost of transport

    DEFF Research Database (Denmark)

    Maresh, Jennifer L; Simmons, Samantha E; Crocker, Daniel E;

    2014-01-01

    Widely ranging marine predators often adopt stereotyped, energy-saving behaviours to minimize the energetic cost of transport while maximizing energy gain. Environmental and anthropogenic disturbances can disrupt energy balance by prompting avoidance behaviours that increase transport costs......, thereby decreasing foraging efficiency. We examined the ability of 12 free-ranging, juvenile northern elephant seals (Mirounga angustirostris) to mitigate the effects of experimentally increased transport costs by modifying their behaviour and/or energy use in a compensatory manner. Under normal......±11 s; Pbehaviours were conserved across treatments, including fixed, rhythmic swimming gaits. Because of this, and because each flipper stroke had a predictable effect on total costs (P

  6. Automatization Aspects of Dyslexia: Speed Limitations in Word Identification, Sensitivity to Increasing Task Demands, and Orthographic Compensation.

    Science.gov (United States)

    van der Leij, Aryan; van Daal, Victor H. P.

    1999-01-01

    Ten students (age 10) with dyslexia were compared to 10 chronological-age controls and 20 reading-age controls. Response latencies of the students with dyslexia were slower when familiar words, letter clusters, and nonwords had to be named. A larger word-frequency effect and larger word-length effect indicate difficulty with increasing task…

  7. New Variants of Tomato Thymidine Kinase 1 Selected for Increased Sensitivity of E. coli KY895 towards Azidothymidine

    DEFF Research Database (Denmark)

    Christiansen, Louise Slot; Egeblad, Louise; Munch-Petersen, Birgitte;

    2015-01-01

    by random protein engineering for suicide gene therapy with the NA azidothymidine (AZT).We describe their selection, recombinant production and a subsequent kinetic and biochemical characterization. Their improved performance in killing of E. coli KY895 is accompanied by an increase in specificity...

  8. Mechanism of production increasing of coalbed gas for the pinnate horizontal well and sensitivity effect of parameters on gas production

    Institute of Scientific and Technical Information of China (English)

    ZHANG Dongli; WANG Xinhai

    2005-01-01

    The mechanism of production increasing for the pinnate horizontal well is analyzed with the simulation technique. It is pointed out that the whole horizontal wellbore spreading widely and evenly in coal layers makes the stratum pressure drop evenly and fast, which increases the chance of desorption and diffusion and area controlled. This is the basic reason that the pinnate horizontal well can increase production. How such stratum parameters as permeability, Langmuir constants and adsorption time constant affect the gas production for the pinnate horizontal well is also studied with numerical simulations. Either for the vertical well or the pinnate horizontal well, bigger stratum permeability, steeper relative permeability curve, smaller residual gas saturation, higher gas content and stratum pressure are more favorable for gas production increasing. Langmuir constants decide the change of desorption quantity and influence the gas production through changing the extent of steep of isothermal adsorption curves in the pressure dropping area. The adsorption time constant only influences the time that gas production arrives at the maximum value for the vertical well, but it almost has no influence on the gas production for the pinnate horizontal well because the equivalent adsorption time constant is reduced.

  9. Brassinosteroid-induced CO{sub 2} assimilation is associated with increased stability of redox-sensitive photosynthetic enzymes in the chloroplasts in cucumber plants

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Yu Ping; Cheng, Fei; Zhou, Yan Hong; Xia, Xiao Jian; Mao, Wei Hua; Shi, Kai [Department of Horticulture, Zijingang Campus, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058 (China); Chen, Zhi Xiang [Department of Horticulture, Zijingang Campus, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058 (China); Department of Botany and Plant Pathology, Purdue University, West Lafayette, IN 47907-2054 (United States); Yu, Jing Quan, E-mail: jqyu@zju.edu.cn [Department of Horticulture, Zijingang Campus, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058 (China); Key Laboratory of Horticultural Plants Growth, Development and Quality Improvement, Ministry of Agriculture of China, Yuhangtang Road 866, Hangzhou 310058 (China)

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer Activity of certain Calvin cycle enzymes and CO{sub 2} assimilation are induced by BRs. Black-Right-Pointing-Pointer BRs upregulate the activity of the ascorbate-glutathione cycle in the chloroplasts. Black-Right-Pointing-Pointer BRs increase the chloroplast thiol reduction state. Black-Right-Pointing-Pointer A BR-induced reducing environment increases the stability of photosynthetic enzymes. -- Abstract: Brassinosteroids (BRs) play important roles in plant growth, development, photosynthesis and stress tolerance; however, the mechanism underlying BR-enhanced photosynthesis is currently unclear. Here, we provide evidence that an increase in the BR level increased the quantum yield of PSII, activities of Rubisco activase (RCA) and fructose-1,6-bisphosphatase (FBPase), and CO{sub 2} assimilation. BRs upregulated the transcript levels of genes and activity of enzymes involved in the ascorbate-glutathione cycle in the chloroplasts, leading to an increased ratio of reduced (GSH) to oxidized (GSSG) glutathione in the chloroplasts. An increased GSH/GSSG ratio protected RCA from proteolytic digestion and increased the stability of redox-sensitive enzymes in the chloroplasts. These results strongly suggest that BRs are capable of regulating the glutathione redox state in the chloroplasts through the activation of the ascorbate-glutathione cycle. The resulting increase in the chloroplast thiol reduction state promotes CO{sub 2} assimilation, at least in part, by enhancing the stability and activity of redox-sensitive photosynthetic enzymes through post-translational modifications.

  10. Low dose influenza virus challenge in the ferret leads to increased virus shedding and greater sensitivity to oseltamivir.

    Directory of Open Access Journals (Sweden)

    Anthony C Marriott

    Full Text Available Ferrets are widely used to study human influenza virus infection. Their airway physiology and cell receptor distribution makes them ideal for the analysis of pathogenesis and virus transmission, and for testing the efficacy of anti-influenza interventions and vaccines. The 2009 pandemic influenza virus (H1N1pdm09 induces mild to moderate respiratory disease in infected ferrets, following inoculation with 106 plaque-forming units (pfu of virus. We have demonstrated that reducing the challenge dose to 102 pfu delays the onset of clinical signs by 1 day, and results in a modest reduction in clinical signs, and a less rapid nasal cavity innate immune response. There was also a delay in virus production in the upper respiratory tract, this was up to 9-fold greater and virus shedding was prolonged. Progression of infection to the lower respiratory tract was not noticeably delayed by the reduction in virus challenge. A dose of 104 pfu gave an infection that was intermediate between those of the 106 pfu and 102 pfu doses. To address the hypothesis that using a more authentic low challenge dose would facilitate a more sensitive model for antiviral efficacy, we used the well-known neuraminidase inhibitor, oseltamivir. Oseltamivir-treated and untreated ferrets were challenged with high (106 pfu and low (102 pfu doses of influenza H1N1pdm09 virus. The low dose treated ferrets showed significant delays in innate immune response and virus shedding, delayed onset of pathological changes in the nasal cavity, and reduced pathological changes and viral RNA load in the lung, relative to untreated ferrets. Importantly, these observations were not seen in treated animals when the high dose challenge was used. In summary, low dose challenge gives a disease that more closely parallels the disease parameters of human influenza infection, and provides an improved pre-clinical model for the assessment of influenza therapeutics, and potentially, influenza vaccines.

  11. Spontaneous nisin-resistant Listeria monocytogenes mutants with increased expression of a putative penicillin-binding protein and their sensitivity to various antibiotics.

    Science.gov (United States)

    Gravesen, A; Sørensen, K; Aarestrup, F M; Knøchel, S

    2001-01-01

    A concern regarding the use of bacteriocins, as for example the lantibiotic nisin, for biopreservation of certain food products is the possibility of resistance development and potential cross-resistance to antibiotics in the target organism. The genetic basis for nisin resistance development is as yet unknown. We analyzed changes in gene expression following nisin resistance development in Listeria monocytogenes 412 by restriction fragment differential display. The mutant had increased expression of a protein with strong homology to the glycosyltransferase domain of high-molecular-weight penicillin-binding proteins (PBPs), a histidine protein kinase, a protein of unknown function, and ClpB (putative functions from homology). The three former proteins had increased expression in a total of six out of 10 independent mutants originating from five different wild-type strains, indicating a prevalent nisin resistance mechanism under the employed isolation conditions. Increased expression of the putative PBP may affect the cell wall composition and thereby alter the sensitivity to cell wall-targeting compounds. The mutants had an isolate-specific increase in sensitivity to different beta-lactams and a slight decrease in sensitivity to another lantibiotic, mersacidin. A model incorporating these observations is proposed based on current knowledge of nisin's mode of action.

  12. Calcium sensitivity and the Frank-Starling mechanism of the heart are increased in titin N2B region deficient mice

    Science.gov (United States)

    Lee, Eun-Jeong; Peng, Jun; Radke, Michael; Gotthardt, Michael; Granzier, Henk L

    2010-01-01

    Previous work suggests that titin-based passive tension is a factor in the Frank-Starling mechanism of the heart, by increasing length-dependent activation (LDA) through an increase in calcium sensitivity at long sarcomere length. We tested this hypothesis in a mouse model (N2B KO model) in which titin-based passive tension is elevated as a result of the excision of the N2B element, one of cardiac titin’s spring elements. LDA was assessed by measuring the active tension-pCa (−log[Ca2+]) relationship at sarcomere length (SLs) of 1.95, 2.10 and 2.30 µm in WT and N2B KO skinned myocardium. LDA was positively correlated with titin-based passive tension, due to an increase in calcium sensitivity at the longer SLs in the KO. For example, at pCa 6.0 the KO:WT tension ratio was 1.28 ± 0.07 and 1.42 ± 0.04 at SLs of 2.1 and 2.3 µm, respectively. There was no difference in protein expression or phosphorylation of sarcomeric proteins. We also measured the calcium sensitivity after PKA treating the skinned muscle and found that titin-based passive tension was also now correlated with LDA, with a slope that was significantly increased compared to no PKA treatment. Finally, we performed isolated heart experiments and measured the Frank-Starling relation (slope of developed wall stress-LV volume relation) as well as diastolic stiffness (slope of diastolic wall stress – volume relation). The FSM was more pronounced in the N2B KO hearts and the slope of the FSM correlated with diastolic stiffness. These findings support that titin-based passive tension triggers an increase in calcium sensitivity at long sarcomere length, thereby playing an important role in the Frank-Starling mechanism of the heart. PMID:20507834

  13. Calcium sensitivity and the Frank-Starling mechanism of the heart are increased in titin N2B region-deficient mice.

    Science.gov (United States)

    Lee, Eun-Jeong; Peng, Jun; Radke, Michael; Gotthardt, Michael; Granzier, Henk L

    2010-09-01

    Previous work suggests that titin-based passive tension is a factor in the Frank-Starling mechanism of the heart, by increasing length-dependent activation (LDA) through an increase in calcium sensitivity at long sarcomere length. We tested this hypothesis in a mouse model (N2B KO model) in which titin-based passive tension is elevated as a result of the excision of the N2B element, one of cardiac titin's spring elements. LDA was assessed by measuring the active tension-pCa (-log[Ca(2+)]) relationship at sarcomere length (SLs) of 1.95, 2.10, and 2.30 microm in WT and N2B KO skinned myocardium. LDA was positively correlated with titin-based passive tension due to an increase in calcium sensitivity at the longer SLs in the KO. For example, at pCa 6.0, the KO:WT tension ratio was 1.28+/-0.07 and 1.42+/-0.04 at SLs of 2.1 and 2.3 microm, respectively. There was no difference in protein expression or total phosphorylation of sarcomeric proteins. We also measured the calcium sensitivity after PKA treating the skinned muscle and found that titin-based passive tension was also now correlated with LDA, with a slope that was significantly increased compared to no PKA treatment. Finally, we performed isolated heart experiments and measured the Frank-Starling relation (slope of developed wall stress-LV volume relation) as well as diastolic stiffness (slope of diastolic wall stress-volume relation). The FSM was more pronounced in the N2B KO hearts and the slope of the FSM correlated with diastolic stiffness. These findings support that titin-based passive tension triggers an increase in calcium sensitivity at long sarcomere length, thereby playing an important role in the Frank-Starling mechanism of the heart.

  14. Decreased hepatic peroxisome proliferator-activated receptor-γ contributes to increased sensitivity to endotoxin in obstructive jaundice

    Institute of Scientific and Technical Information of China (English)

    Xin Lv; Jian-Gang Song; Hong-Hai Li; Jun-Ping Ao; Ping Zhang; Ye-Sheng Li; Shao-Li Song; Xiang-Rui Wang

    2011-01-01

    AIM:To investigate the role of hepatic peroxisome proliferator-activated receptor -γ (PPAR-γ) in increased susceptibility to endotoxin-induced toxicity in rats with bile duct ligation during endotoxemia. METHODS: Male Sprague-Dawley rats were subjected to bile duct ligation (BDL). Sham-operated animals served as controls. DNA binding were determined by polymerase chain reaction, Western blotting analysis, and electrophoretic mobility shift assay, respectively. BDL and sham-operated rats received a non-lethal dose of intraperitoneal lipopolysaccharide (LPS) injection (3 mg/kg, i.p.). Additionally, the potential beneficial effects of the PPAR-γ agonist rosiglitazone were determined in BDL and sham-operated rats treated with a non-lethal dose of LPS. Survival was assessed in BDL rats treated with a non-lethal dose of LPS and in sham-operated rats treated at a lethal dose of LPS (6 mg/kg, i.p.). RESULTS: PPAR-γ activity in rats undergoing BDL was significantly lower than in the sham-controls. Hepatic PPAR-γ gene expression was downregulated at both the mRNA and protein levels. In a parallel group, serum levels of pro-inflammatory cytokines were nearly undetectable in the sham-operated rats. When challenged with a non-lethal dose of LPS (3 mg/kg), the BDL rats had approximately a 2.4-fold increase in serum IL-6, a 2.7 fold increase in serum TNF-α, 2.2-fold increase in serum IL-1 and 4.2-fold increase in serum ALT. The survival rate was significantly lower as compared with that in sham-operated group. Additionally, rosiglitazone significantly reduced the concentration of TNF-α, IL-1β, IL-6 and ALT in sham-operated rats, but not in BDL rats, in response to LPS (3 mg/kg). Also, the survival was improved by rosiglitazone in sham-operated rats challenged with a lethal dose of LPS, but not in BDL rats, even with a non-lethal dose of LPS (3 mg/kg). CONCLUSION: Obstructive jaundice downregulates hepatic PPAR-γ expression, which in turn may contribute to

  15. Network single-walled carbon nanotube-field effect transistors (SWNT-FETs) with increased Schottky contact area for highly sensitive biosensor applications.

    Science.gov (United States)

    Byon, Hye Ryung; Choi, Hee Cheul

    2006-02-22

    Highly sensitive single-walled carbon nanotube-field effect transistor (SWNT-FET) devices, which detect protein adsorptions and specific protein-protein interactions at 1 pM concentrations, have been achieved. The detection limit has been improved 104-fold compared to the devices fabricated by photolithography. The substantially increased sensitivity is mainly due to the increased Schottky contact area which accommodates relatively more numbers of proteins even at very low concentration. The augmented number of proteins adsorbed on a device induces instant modulation of the work function of metal contact electrodes, which eventually changes the conductance of the device. Such devices have been attained by addressing metal electrodes on network-type SWNTs using a shadow mask on a tilted angle sample stage. The shadow mask allows metals to penetrate underneath the mask efficiently, therefore forming a thin and wide Schottky contact area on SWNT channels.

  16. Impact of air pollution on age and gender related increase in cough reflex sensitivity of healthy children in Slovakia.

    Directory of Open Access Journals (Sweden)

    Silvia eDemoulin-Alexikova

    2016-02-01

    Full Text Available Background. Numerous studies show higher cough reflex sensitivity (CRS and cough outcomes in children compared to adults and in females compared to males. Despite close link that exists between cough and environment the potential influence of environmental air pollution on age- and gender -related differences in cough has not been studied yet. Purpose. The purpose of our study was to analyse whether the effects of exposure to environmental tobacco smoke (ETS from parental smoking and PM10 from living in urban area are implied in age- and gender-related differences in cough outcomes of healthy, non asthmatic children. Assessment of CRS using capsaicin and incidence of dry and wet cough was performed in 290 children (mean age 13.3±2.6 yrs (138 females/152 males.Results. CRS was significantly higher in girls exposed to ETS [22.3 μmol/l (9.8 – 50.2 μmol/l] compared to not exposed girls [79.9 μmol/l (56.4 – 112.2 μmol/l, p=0.02] as well as compared to exposed boys [121.4 μmol/l (58.2 – 253.1 μmol/l, p=0.01]. Incidence of dry cough lasting more than 3 weeks was significantly higher in exposed compared to not exposed girls. CRS was significantly higher in school-aged girls living in urban area [22.0 μmol/l (10.6 – 45.6 μmol/l] compared to school-aged girls living in rural area [215.9 μmol/l (87.3 – 533.4 μmol/l; p=0.003], as well as compared to teenage girls living in urban area [108.8 μmol/l (68.7 – 172.9 μmol/l; p=0.007]. No CRS differences were found between urban and rural boys when controlled for age group. No CRS differences were found between school-aged and teenage boys when controlled for living area. Conclusions. Our results have shown that the effect of ETS on CRS was gender specific, linked to female gender and the effect of PM10 on CRS was both gender and age specific, related to female gender and school-age. We suggest that age and gender related differences in incidence of cough and CRS might be, at least

  17. Experimental evolution of defense against a competitive mold confers reduced sensitivity to fungal toxins but no increased resistance in Drosophila larvae

    Directory of Open Access Journals (Sweden)

    Trienens Monika

    2011-07-01

    Full Text Available Abstract Background Fungal secondary metabolites have been suggested to function as chemical defenses against insect antagonists, i.e. predators and competitors. Because insects and fungi often compete for dead organic material, insects may achieve protection against fungi by reducing sensitivity to fungal chemicals. This, in turn, may lead to increased resistance allowing insects better to suppress the spread of antagonistic but non-pathogenic microbes in their habitat. However, it remains controversial whether fungal toxins serve as a chemical shield that selects for insects that are less sensitive to toxins, and hence favors the evolution of insect resistance against microbial competitors. Results To examine the relationship between the ability to survive competition with toxic fungi, sensitivity to fungal toxins and resistance, we created fungal-selected (FS replicated insect lines by exposing Drosophila melanogaster larvae to the fungal competitor Aspergillus nidulans over 26 insect generations. Compared to unselected control lines (UC, larvae from the FS lines had higher survival rates in the presence of A. nidulans indicating selection for increased protection against the fungal antagonist. In line with our expectation, FS lines were less susceptible to the A. nidulans mycotoxin Sterigmatocystin. Of particular interest is that evolved protection against A. nidulans and Sterigmatocytin was not correlated with increased insect survival in the presence of other fungi and mycotoxins. We found no evidence that FS lines were better at suppressing the expansion of fungal colonies but observed a trend towards a less detrimental effect of FS larvae on fungal growth. Conclusion Antagonistic but non-pathogenic fungi favor insect variants better protected against the fungal chemical arsenal. This highlights the often proposed but experimentally underexplored importance of secondary metabolites in driving animal-fungus interactions. Instead of

  18. Sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation will increase in lipopolysaccharide-induced inflammation in vitro model

    OpenAIRE

    Zuo, Wen-Qi; Hu, Yu-Juan; Yang, Yang; Zhao, Xue-Yan; Zhang,Yuan-Yuan; Kong, Wen; Kong, Wei-Jia

    2015-01-01

    Background With the increasing popularity of mobile phones, the potential hazards of radiofrequency electromagnetic radiation (RF-EMR) on the auditory system remain unclear. Apart from RF-EMR, humans are also exposed to various physical and chemical factors. We established a lipopolysaccharide (LPS)-induced inflammation in vitro model to investigate whether the possible sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation (at specific absorption ra...

  19. Semicoherent searches for continuous gravitational waves: improving robustness versus transient disturbances and increasing sensitivity to transient signals

    CERN Document Server

    Keitel, David

    2015-01-01

    The vulnerability of standard detection methods for long-duration quasi-monochromatic gravitational waves from non-axisymmetric rotating neutron stars ('continuous waves', CWs) to single-detector instrumental artifacts was addressed in past work [Keitel, Prix, Papa, Leaci and Siddiqi, Phys. Rev. D 89, 064023 (2014)] by a Bayesian approach. An explicit model of persistent single-detector disturbances led to a generalized detection statistic with improved robustness against such artifacts. Since many strong outliers in semicoherent searches of LIGO data are caused by transient disturbances that last only a few hours, we extend this approach to cover transient disturbances, and demonstrate increased robustness in realistic simulated data. Besides long-duration CWs, neutron stars could also emit transient signals which, for a limited time, also follow the CW signal model (tCWs). As a pragmatic alternative to specialized transient searches, we demonstrate how to make standard semicoherent CW searches more sensitiv...

  20. H-ras transformation sensitizes volume-activated anion channels and increases migratory activity of NIH3T3 fibroblasts

    DEFF Research Database (Denmark)

    Schneider, Linda; Klausen, Thomas K; Stock, Christian;

    2008-01-01

    The expression of the H-ras oncogene increases the migratory activity of many cell types and thereby contributes to the metastatic behavior of tumor cells. Other studies point to an involvement of volume-activated anion channels (VRAC) in (tumor) cell migration. In this paper, we tested whether...... VRACs are required for the stimulation of cell migration upon expression of the H-ras oncogene. We compared VRAC activation and migration of wild-type and H-ras-transformed NIH3T3 fibroblasts by means of patch-clamp techniques and time-lapse video microscopy. Both cell types achieve the same degree...... of VRAC activation upon maximal stimulation, induced by reducing extracellular osmolarity from 300 to 190 mOsm/l. However, upon physiologically relevant reductions in extracellular osmolarity (275 mOsm/l), the level of VRAC activation is almost three times higher in H-ras-transformed compared to wild...

  1. Heterozygosity in the glutathione synthesis gene Gclm increases sensitivity to diesel exhaust particulate induced lung inflammation in mice

    Science.gov (United States)

    Weldy, Chad S.; White, Collin C.; Wilkerson, Hui-Wen; Larson, Timothy V.; Stewart, James A.; Gill, Sean E.; Parks, William C.; Kavanagh, Terrance J.

    2012-01-01

    Context Inhalation of ambient fine particulate matter (PM2.5) is associated with adverse respiratory and cardiovascular effects. A major fraction of PM2.5 in urban settings is diesel exhaust particulate (DEP), and DEP-induced lung inflammation is likely a critical event mediating many of its adverse health effects. Oxidative stress has been proposed to be an important factor in PM2.5-induced lung inflammation, and the balance between pro- and antioxidants is an important regulator of this inflammation. An important intracellular antioxidant is the tripeptide thiol glutathione (GSH). Glutamate cysteine ligase (GCL) carries out the first step in GSH synthesis. In humans, relatively common genetic polymorphisms in both the catalytic (Gclc) and modifier (Gclm) subunits of GCL have been associated with increased risk for lung and cardiovascular diseases. Objective This study was aimed to determine the effects of Gclm expression on lung inflammation following DEP exposure in mice. Materials and methods We exposed Gclm wild type, heterozygous, and null mice to DEP via intranasal instillation and assessed lung inflammation as determined by neutrophils and inflammatory cytokines in lung lavage, inflammatory cytokine mRNA levels in lung tissue, as well as total lung GSH, Gclc, and Gclm protein levels. Results The Gclm heterozygosity was associated with a significant increase in DEP-induced lung inflammation when compared to that of wild type mice. Discussion and conclusion This finding indicates that GSH synthesis can mediate DEP-induced lung inflammation and suggests that polymorphisms in Gclm may be an important factor in determining adverse health outcomes in humans following inhalation of PM2.5. PMID:21967497

  2. Long-term Temozolomide Treatment Induces Marked Amino Metabolism Modifications and an Increase in TMZ Sensitivity in Hs683 Oligodendroglioma Cells

    Directory of Open Access Journals (Sweden)

    Delphine Lamoral-Theys

    2010-01-01

    Full Text Available Gliomas account for more than 50% of all primary brain tumors. The worst prognosis is associated with gliomas of astrocytic origin, whereas gliomas with an oligodendroglial origin offer higher sensitivity to chemotherapy, especially when oligodendroglioma cells display 1p19q deletions. Temozolomide (TMZ provides therapeutic benefits and is commonly used with radiotherapy in highly malignant astrocytic tumors, including glioblastomas. The actual benefits of TMZ during long-term treatment in oligodendroglioma patients have not yet been clearly defined. In this study, we have investigated the effects of such a long-term TMZ treatment in the unique Hs683 oligodendroglioma model. We have observed increased TMZ sensitivity of Hs683 orthotopic tumors that were previously treated in vitro with months of progressive exposure to increasing TMZ concentrations before being xenografted into the brains of immunocompromised mice. Whole-genome and proteomic analyses have revealed that this increased TMZ sensitivity of Hs683 oligodendroglioma cells previously treated for long periods with TMZ can be explained, at least partly, by a TMZ-induced p38-dependant dormancy state, which in turn resulted in changes in amino acid metabolism balance, in growth delay, and in a decrease in Hs683 oligodendroglioma cell-invasive properties. Thus, long-term TMZ treatment seems beneficial in this Hs683 oligodendroglioma model, which revealed itself unable to develop resistance against TMZ.

  3. New Variants of Tomato Thymidine Kinase 1 Selected for Increased Sensitivity of E. coli KY895 towards Azidothymidine

    Energy Technology Data Exchange (ETDEWEB)

    Slot Christiansen, Louise [Department of Biology, Lund University, Lund 22362 (Sweden); Lund Protein Production Platform, Lund University, Lund 22362 (Sweden); Egeblad, Louise [Lund Protein Production Platform, Lund University, Lund 22362 (Sweden); Munch-Petersen, Birgitte [Department of Science, Systems and Models, Roskilde University, Roskilde 4000 (Denmark); Piškur, Jure [Department of Biology, Lund University, Lund 22362 (Sweden); Knecht, Wolfgang, E-mail: Louise.Slot_Christiansen@biol.lu.se [Department of Biology, Lund University, Lund 22362 (Sweden); Lund Protein Production Platform, Lund University, Lund 22362 (Sweden)

    2015-06-08

    Nucleoside analogues (NA) are prodrugs that are phosphorylated by deoxyribonucleoside kinases (dNKs) as the first step towards a compound toxic to the cell. During the last 20 years, research around dNKs has gone into new organisms other than mammals and viruses. Newly discovered dNKs have been tested as enzymes for suicide gene therapy. The tomato thymidine kinase 1 (ToTK1) is a dNK that has been selected for its in vitro kinetic properties and then successfully been tested in vivo for the treatment of malignant glioma. We present the selection of two improved variants of ToTK1 generated by random protein engineering for suicide gene therapy with the NA azidothymidine (AZT). We describe their selection, recombinant production and a subsequent kinetic and biochemical characterization. Their improved performance in killing of E. coli KY895 is accompanied by an increase in specificity for the NA AZT over the natural substrate thymidine as well as a decrease in inhibition by dTTP, the end product of the nucleoside salvage pathway for thymidine. The understanding of the enzymatic properties improving the variants efficacy is instrumental to further develop dNKs for use in suicide gene therapy.

  4. A higher inherent trait for fearfulness is associated with increased anxiety-like behaviours and diazepam sensitivity in Japanese quail.

    Science.gov (United States)

    Boulay, J; Chaillou, E; Bertin, A; Constantin, P; Arnould, C; Leterrier, C; Calandreau, L

    2013-01-15

    This study tested whether lines of Japanese quails divergently selected for a fear response, the tonic immobility, might constitute a reliable bird model for studying anxiety. Previous studies demonstrated that the selection modifies the general underlying emotionality of the birds rather than exerting its effect only on tonic immobility. The behavioural effects of intraperitoneal injections of diazepam, an anxiolytic drug, were assessed in two lines of quail selected either for their short (STI) or long (LTI) duration of tonic immobility. Effects of diazepam were examined in two tests used for measuring emotionality in birds, the open field and the tonic immobility tests. After being placed in the centre of the open field, birds with a high emotionality (LTI quails) stayed longer in the centre of the apparatus than STI quail. Diazepam had anxiolytic effect in LTI birds as it increased the time spent in the outer area. This effect of diazepam appears to be selective because the drug has no effect on other behaviours such as distress calls or escape attempts. The drug has also no effect on the tonic immobility response in any of the two lines. These findings reveal an "anxiogenic" trait of LTI birds in the open field test that can be modulated by the administration of an anxiolytic drug. Therefore quails selected for LTI and STI represent a valuable model to study the mechanisms underlying anxiety in birds.

  5. Evolutionarily Successful Asian 1 Dengue Virus 2 Lineages Contain One Substitution in Envelope That Increases Sensitivity to Polyclonal Antibody Neutralization.

    Science.gov (United States)

    Wang, Chunling; Katzelnick, Leah C; Montoya, Magelda; Hue, Kien Duong Thi; Simmons, Cameron P; Harris, Eva

    2016-03-15

    The 4 dengue virus serotypes (DENV-1-4) cause the most prevalent mosquito-borne viral disease of humans worldwide. DENV-2 Asian 1 (A1) genotype viruses replaced the Asian-American (AA) genotype in Vietnam and Cambodia, after which A1 viruses containing Q or M at envelope (E) residue 160 became more prevalent than those with residue 160K in both countries (2008-2011). We investigated whether these substitutions conferred a fitness advantage by measuring neutralizing antibody titer against reporter virus particles (RVPs) representing AA, A1-160K, A1-160Q, and A1-160M, using patient sera from Vietnam and a well-characterized Nicaraguan cohort. Surprisingly, we found that A1-160Q and A1-160M RVPs were better neutralized by heterologous antisera than A1-160K. Despite this, Vietnamese patients infected with A1-160Q or A1-160M viruses had higher viremia levels than those infected with A1-160K. We thus found that independent lineages in Vietnam and Cambodia acquired a substitution in E that significantly increased polyclonal neutralization but nonetheless were successful in disseminating and infecting human hosts.

  6. Order of magnitude sensitivity increase in X-ray Fluorescence Computed Tomography (XFCT) imaging with an optimized spectro-spatial detector configuration: theory and simulation.

    Science.gov (United States)

    Ahmad, Moiz; Bazalova, Magdalena; Xiang, Liangzhong; Xing, Lei

    2014-05-01

    The purpose of this study was to increase the sensitivity of XFCT imaging by optimizing the data acquisition geometry for reduced scatter X-rays. The placement of detectors and detector energy window were chosen to minimize scatter X-rays. We performed both theoretical calculations and Monte Carlo simulations of this optimized detector configuration on a mouse-sized phantom containing various gold concentrations. The sensitivity limits were determined for three different X-ray spectra: a monoenergetic source, a Gaussian source, and a conventional X-ray tube source. Scatter X-rays were minimized using a backscatter detector orientation (scatter direction > 110(°) to the primary X-ray beam). The optimized configuration simultaneously reduced the number of detectors and improved the image signal-to-noise ratio. The sensitivity of the optimized configuration was 10 μg/mL (10 pM) at 2 mGy dose with the mono-energetic source, which is an order of magnitude improvement over the unoptimized configuration (102 pM without the optimization). Similar improvements were seen with the Gaussian spectrum source and conventional X-ray tube source. The optimization improvements were predicted in the theoretical model and also demonstrated in simulations. The sensitivity of XFCT imaging can be enhanced by an order of magnitude with the data acquisition optimization, greatly enhancing the potential of this modality for future use in clinical molecular imaging.

  7. Sensitivity to stress-induced reproductive dysfunction is associated with a selective but not a generalized increase in activity of the adrenal axis.

    Science.gov (United States)

    Herod, S M; Dettmer, A M; Novak, M A; Meyer, J S; Cameron, J L

    2011-01-01

    Stress-induced reproductive dysfunction is a relatively common cause of infertility in women. In response to everyday life stress, some individuals readily develop reproductive dysfunction (i.e., they are stress sensitive), whereas others are more stress resilient. Female cynomolgus monkeys, when exposed to mild combined psychosocial and metabolic stress (change in social environment + 20% reduced calorie diet), can be categorized as stress sensitive (SS; they rapidly become anovulatory in response to stress), medium stress resilient (MSR; they slowly become anovulatory in response to prolonged stress), or highly stress resilient (HSR; they maintain normal menstrual cycles in response to stress). In this study, we examined whether increased sensitivity to stress-induced reproductive dysfunction is associated with elevated adrenal axis activity by measuring 1) the diurnal release of ACTH and cortisol, 2) ACTH and cortisol in response to an acute psychological stress, 3) the percent suppression of cortisol in response to dexamethasone negative feedback, 4) the diurnal release of ACTH and cortisol following exposure to mild psychosocial and metabolic stress, 5) the concentration of cortisol in hair, and 6) adrenal weight. SS monkeys (n = 5) did not differ from MSR (n = 5) or HSR (n = 7) monkeys in any measurement of baseline HPA axis activity or the integrated measurements of chronic HPA axis activity. However, MSR + SS monkeys (n = 10) did secrete more cortisol than HSR monkeys during the daytime hours (1000-1800) following exposure to a novel social environment and reduced diet. We conclude that increased activity of the HPA axis is unlikely to be the primary mechanism causing increased sensitivity to stress-induced reproductive dysfunction.

  8. Increased insulin binding to adipocytes and monocytes and increased insulin sensitivity of glucose transport and metabolism in adipocytes from non-insulin-dependent diabetics after a low-fat/high-starch/high-fiber diet.

    Science.gov (United States)

    Hjøllund, E; Pedersen, O; Richelsen, B; Beck-Nielsen, H; Sørensen, N S

    1983-11-01

    Nine non-insulin-dependent diabetics were studied before and after 3 weeks on an isoenergetic high-fiber/high-starch/low-fat diet (alternative diet), and nine non-insulin-dependent diabetics were studied on their usual diet. In the group that ate the alternative diet, the intake of fiber and starch increased 120% and 53%, whereas fat intake decreased 31%. Diabetes control improved as demonstrated by decreased fasting plasma glucose (P less than 0.05) and 24-hour urinary glucose excretion (P less than 0.05). The in vivo insulin action increased (KIVITT increased, P less than 0.05) with no change in fasting serum insulin levels. In fat cells obtained from patients in the alternative-diet group, insulin receptor binding increased (P less than 0.05) after the change of diet. Insulin binding to purified monocytes (more than 95% monocytes) also increased (P less than 0.05), whereas no change was found in insulin binding to erythrocytes. When lipogenesis was studied at a tracer glucose concentration at which glucose transport seems to be rate limiting, insulin sensitivity increased (P less than 0.02). This is the predicted consequence of increased receptor binding. Moreover, when CO2 production and lipogenesis were studied at a higher glucose concentration, where steps beyond transport seem to be rate limiting for glucose metabolism, increased insulin sensitivity was also observed. In contrast, no change was found in maximal insulin responsiveness. Fat and blood cells from the patients who continued on their usual diet showed no changes of the mentioned quantities.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Exon-skipping strategy by ratio modulation between cytoprotective versus pro-apoptotic clusterin forms increased sensitivity of LNCaP to cell death.

    Directory of Open Access Journals (Sweden)

    Abdellatif Essabbani

    Full Text Available BACKGROUND: In prostate cancer the secreted form of clusterin (sCLU has been described as an anti-apoptotic protein whose expression is increased after therapeutic intervention, whereas, the nuclear protein form nCLU was reported to have pro-apoptotic properties. METHODOLOGY: In order to provide new therapeutic approaches targeting CLU, we developed a strategy based on exon skipping by using a lentiviral construct to preferentially induce the nuclear spliced form of the protein. The molecular construct was transduced in LNCaP cells for testing the modulation of sensitivity of the transduced cells to pro-apoptotic stress. RESULTS AND CONCLUSIONS: We showed an increase of nCLU/sCLU expression ratio in the prostate cancer cell line "LNCaP" after lentiviral vector-U7 nCLU transduction. Moreover, we showed a significant inhibition of cell proliferation in nCLU-U7 LNCaP cells after treatment with cisplatin and after exposure to ionizing radiation compared to control cells. Finally, we showed that nCLU-U7 LNCaP cells exposure to UV-C significantly reduced an increase of cell death compared to control. Finally, we showed that modulating nCLU expression had profound impact on Ku70/Bax interaction as well as Rad17 expression which could be a key mechanism in sensitizing cells to cell death. In conclusion, this is the first report showing that increasing of nCLU/sCLU expression ratio by using an "on demand alternative splicing" strategy successfully increased sensitivity to radiotherapy and chemotherapy of prostate cancer cells.

  10. Dietary intervention increases n-3 long-chain polyunsaturated fatty acids in skeletal muscle membrane phospholipids of obese subjects. Implications for insulin sensitivity

    DEFF Research Database (Denmark)

    Haugaard, S.B.; Madsbad, S.; Høy, Carl-Erik;

    2006-01-01

    Objective Cross-sectional studies suggest that the fatty acid (FA) composition of phospholipids in skeletal muscle cell membrane may modulate insulin sensitivity in humans. We examined the impact of a hypocaloric low-fat dietary intervention on membrane FA composition and insulin sensitivity...... analysis that included changes in weight, fat mass, waist circumference, plasma lipids, PUFA, SFA and long-chain PUFAn-3 indicated that SFA and long-chain PUFAn-3 were independent predictors of HOMA-IR (R-2 = 0.33, P dietary intervention programme increased....... Design Muscle membrane FA profiles were determined in muscle (vastus lateralis) biopsies from 21 obese subjects before and after 6 months of dietary restriction. Diet instructions emphasized low intake of FA of marine origin by recommending lean fish and prohibiting fatty fish and fish oil supplements...

  11. Dietary intervention increases n-3 long-chain polyunsaturated fatty acids in sceletal muscle membrane phospholipids of obese subjects. Inplications for insulin sensitivity

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Madsbad, Sten; Høy, C-E;

    2006-01-01

    OBJECTIVE: Cross-sectional studies suggest that the fatty acid (FA) composition of phospholipids in skeletal muscle cell membrane may modulate insulin sensitivity in humans. We examined the impact of a hypocaloric low-fat dietary intervention on membrane FA composition and insulin sensitivity...... that included changes in weight, fat mass, waist circumference, plasma lipids, PUFA, SFA and long-chain PUFAn-3 indicated that SFA and long-chain PUFAn-3 were independent predictors of HOMA-IR (R(2)=0.33, Pdietary intervention programme increased incorporation of long....... DESIGN Muscle membrane FA profiles were determined in muscle (vastus lateralis) biopsies from 21 obese subjects before and after 6 months of dietary restriction. Diet instructions emphasized low intake of FA of marine origin by recommending lean fish and prohibiting fatty fish and fish oil supplements...

  12. Size-based enrichment of exfoliated tumor cells in urine increases the sensitivity for DNA-based detection of bladder cancer.

    Directory of Open Access Journals (Sweden)

    Elin Andersson

    Full Text Available Bladder cancer is diagnosed by cystoscopy, a costly and invasive procedure that is associated with patient discomfort. Analysis of tumor-specific markers in DNA from sediments of voided urine has the potential for non-invasive detection of bladder cancer; however, the sensitivity is limited by low fractions and small numbers of tumor cells exfoliated into the urine from low-grade tumors. The purpose of this study was to improve the sensitivity for non-invasive detection of bladder cancer by size-based capture and enrichment of tumor cells in urine. In a split-sample set-up, urine from a consecutive series of patients with primary or recurrent bladder tumors (N = 189 was processed by microfiltration using a membrane filter with a defined pore-size, and sedimentation by centrifugation, respectively. DNA from the samples was analyzed for seven bladder tumor-associated methylation markers using MethyLight and pyrosequencing assays. The fraction of tumor-derived DNA was higher in the filter samples than in the corresponding sediments for all markers (p<0.000001. Across all tumor stages, the number of cases positive for one or more markers was 87% in filter samples compared to 80% in the corresponding sediments. The largest increase in sensitivity was achieved in low-grade Ta tumors, with 82 out of 98 cases positive in the filter samples (84% versus 74 out of 98 in the sediments (75%. Our results show that pre-analytic processing of voided urine by size-based filtration can increase the sensitivity for DNA-based detection of bladder cancer.

  13. A model of sensitivity: 1,3-butadiene increases mutant frequencies and genomic damage in mice lacking a functional microsomal epoxide hydrolase gene.

    Science.gov (United States)

    Wickliffe, Jeffrey K; Ammenheuser, Marinel M; Salazar, James J; Abdel-Rahman, Sherif Z; Hastings-Smith, Darlene A; Postlethwait, Edward M; Lloyd, R Stephen; Ward, Jonathan B

    2003-01-01

    The specific role that polymorphisms in xenobiotic metabolizing enzymes play in modulating sensitivity to 1,3-butadiene (BD) genotoxicity has been relatively unexplored. The enzyme microsomal epoxide hydrolase (mEH) is important in detoxifying the mutagenic epoxides of BD (butadiene monoepoxide [BDO], butadiene diepoxide [BDO(2)]). Polymorphisms in the human mEH gene appear to affect the function of the enzyme. We exposed mice with normal mEH activity (WT) and knockout mice without mEH activity (KO) to 20 ppm BD (inhalation) or 30 mg/kg BDO(2) (intraperitoneal [IP] injection). We then compared Hprt mutant frequencies (MFs) among these groups. KO mice exposed to BD exhibited a significant (P damage in WT and KO mice (comet tail moment) following IP exposure to 3 mg/kg and 30 mg/kg BDO(2). KO mice exposed to 3 mg/kg exhibited significantly more DNA damage than controls (7.5-12.1-fold increase) and exposed WT mice (3 mg/kg; 4.8-fold increase). KO mice exposed to 30 mg/kg BDO(2) exhibited significantly more DNA damage than all other groups (2.3-27.9-fold increase). Correlation analysis indicated that a significant, positive relationship (r(2) = 0.92) exists between comet-measured damage and Hprt MFs. The lack of mEH activity increases the genetic sensitivity of mice exposed to BD and BDO(2). This model should facilitate a mechanistic understanding of the observed variation in human genetic sensitivity following exposure to BD.

  14. Inherited macular degeneration-associated mutations in CNGB3 increase the ligand sensitivity and spontaneous open probability of cone cyclic nucleotide-gated channels

    Science.gov (United States)

    Meighan, Peter C.; Peng, Changhong; Varnum, Michael D.

    2015-01-01

    Cyclic nucleotide gated (CNG) channels are a critical component of the visual transduction cascade in the vertebrate retina. Mutations in the genes encoding these channels have been associated with a spectrum of inherited retinal disorders. To gain insight into their pathophysiological mechanisms, we have investigated the functional consequences of several CNGB3 mutations, previously associated with macular degeneration (Y469D and L595F) or complete achromatopsia (S156F, P309L, and G558C), by expressing these subunits in combination with wild-type CNGA3 in Xenopus oocytes and characterizing them using patch-clamp recordings in the inside-out configuration. These mutations did not prevent the formation of functional heteromeric channels, as indicated by sensitivity to block by L-cis-diltiazem. With the exception of S156F, each of the mutant channels displayed electrophysiological properties reflecting enhanced channel activity at physiological concentrations of cGMP (i.e., a gain-of-function phenotype). The increased channel activity produced by these mutations resulted from either increased functional expression levels, or increased sensitivity to cyclic nucleotides. Furthermore, L595F increased the spontaneous open probability in the absence of activating ligand, signifying a ligand independent gain-of-function change. In addition to the CNGB3 disease-associate mutations, we characterized the effects of several common CNGB3 and CNGA3 single-nucleotide polymorphisms (SNPs) on heteromeric CNGA3+CNGB3 channel function. Two of the SNPs examined (A3-T153M, and B3-W234C) produced decreased ligand sensitivity for heteromeric CNG channels. These changes may contribute to background disease susceptibility when combined with other genetic or non-genetic factors. Together, these studies help to define the underlying molecular phenotype for mutations relating to CNG channel disease pathogenesis. PMID:26106334

  15. Inherited macular degeneration-associated mutations in CNGB3 increase the ligand sensitivity and spontaneous open probability of cone cyclic nucleotide-gated channels.

    Directory of Open Access Journals (Sweden)

    Peter eMeighan

    2015-06-01

    Full Text Available Cyclic nucleotide gated (CNG channels are a critical component of the visual transduction cascade in the vertebrate retina. Mutations in the genes encoding these channels have been associated with a spectrum of inherited retinal disorders. To gain insight into their pathophysiological mechanisms, we have investigated the functional consequences of several CNGB3 mutations, previously associated with macular degeneration (Y469D and L595F or complete achromatopsia (S156F, P309L, and G558C, by expressing these subunits in combination with wild-type CNGA3 in Xenopus oocytes and characterizing them using patch-clamp recordings in the inside-out configuration. These mutations did not prevent the formation of functional heteromeric channels, as indicated by sensitivity to block by L-cis-diltiazem. With the exception of S156F, each of the mutant channels displayed electrophysiological properties reflecting enhanced channel activity at physiological concentrations of cGMP (i.e., a gain-of-function phenotype. The increased channel activity produced by these mutations resulted from either increased functional expression levels, or increased sensitivity to cyclic nucleotides. Furthermore, L595F increased the spontaneous open probability in the absence of activating ligand, signifying a ligand independent gain-of-function change. In addition to the CNGB3 disease-associate mutations, we characterized the effects of several common CNGB3 and CNGA3 single-nucleotide polymorphisms (SNPs on heteromeric CNGA3+CNGB3 channel function. Two of the SNPs examined (A3-T153M, and B3-W234C produced decreased ligand sensitivity for heteromeric CNG channels. These changes may contribute to background disease susceptibility when combined with other genetic or nongenetic factors. Together, these studies help to define the underlying molecular phenotype for mutations relating to CNG channel disease pathogenesis.

  16. MiR-122 increases sensitivity of drug-resistant BEL-7402/5-FU cells to 5-fluorouracil via down-regulation of bcl-2 family proteins.

    Science.gov (United States)

    Yin, Jie; Tang, Hui Fang; Xiang, Qiong; Yu, Jia; Yang, Xiao Yang; Hu, Nan; Lei, Xiao Yong

    2011-12-01

    To investigate the changes in drug sensitivity of miR-122 transfected BEL-7402/5-FU cells. MiR-122 and negative miRNA expression vectors were constructed and stably transfected into BEL-7402/5-FU cells. Real-time RT-PCR was used to detect the level of miR-122, Bcl-XL, Bcl-2 and P53 mRNA. Western Blotting was used to detect Bcl-2, Bcl-XL and P53 protein expression. Drug sensitivity of the cells to 5-fluorouracil (5-FU) was analyzed with MTT and flow cytometry. Compared with negative miRNA transfectants or untreated cells, mRNA and protein expression level of Bcl-2, Bcl-XL in stable miR-122 transfectants were decreased. Accordingly, P53 protein expression showed a significant up-regulation; MTT results showed that after incubation with 5-FU, miR-122 transfectants had higher cell inhibitory rates than negative miRNA or untreated cells; flow cytometry results demonstrated that apoptosis rate increased in miR-122 transfected cells, compared with negative miRNA or untreated cells. After addition of 5-FU (10 and 100 micromol/I), miR-122 transfected cells showed higher apoptosis rate than negative miRNA or untreated cells. MiR-122 can specifically down-regulate the expression of Bcl-2 and Bcl-XL, and increase P53 activity in BEL-7402/5-FU cells, which increased cells spontaneous apoptosis and sensitize cells to 5-FU. Therefore, MiR-122 can be used as a potential therapy agent against human hepatoblastoma.

  17. Increased sensitivity to physical activity among individuals with knee osteoarthritis: relation to pain outcomes, psychological factors, and responses to quantitative sensory testing.

    Science.gov (United States)

    Wideman, Timothy H; Finan, Patrick H; Edwards, Robert R; Quartana, Phillip J; Buenaver, Luis F; Haythornthwaite, Jennifer A; Smith, Michael T

    2014-04-01

    Recent findings suggest that certain individuals with musculoskeletal pain conditions have increased sensitivity to physical activity (SPA) and respond to activities of stable intensity with increasingly severe pain. This study aimed to determine the degree to which individuals with knee osteoarthritis (OA) show heightened SPA in response to a standardized walking task and whether SPA cross-sectionally predicts psychological factors, responses to quantitative sensory testing (QST), and different OA-related outcomes. One hundred seven adults with chronic knee OA completed self-report measures of pain, function, and psychological factors, underwent QST, and performed a 6-min walk test. Participants rated their discomfort levels throughout the walking task; an index of SPA was created by subtracting first ratings from peak ratings. Repeated-measure analysis of variance revealed that levels of discomfort significantly increased throughout the walking task. A series of hierarchical regression analyses determined that after controlling for significant covariates, psychological factors, and measures of mechanical pain sensitivity, individual variance in SPA predicted self-report pain and function and performance on the walking task. Analyses also revealed that both pain catastrophizing and the temporal summation of mechanical pain were significant predictors of SPA and that SPA mediated the relationship between catastrophizing and self-reported pain and physical function. The discussion addresses the potential processes contributing to SPA and the role it may play in predicting responses to different interventions for musculoskeletal pain conditions.

  18. Silencing Prx1 and/or Prx5 sensitizes human esophageal cancer cells to ionizing radiation and increases apoptosis via intracellular ROS accumulation

    Institute of Scientific and Technical Information of China (English)

    Mai-cang GAO; Xiao-di JIA; Qi-fei WU; Yan CHENG; Fen-rong CHEN; Jun ZHANG

    2011-01-01

    Aim:To investigate whether down-regulation of peroxiredoxin 1(Prx1)and/or peroxiredoxin 5(Prx5)sensitizes human esophageal cancer cells to ionizing radiation(IR).Methods:Human esophageal carcinoma celllines Eca-109 and TE-1 were used.Prx mRNA expression profiles in Eca-109 and TE-1cells were determined using RT-PCR.Two highly expressed isoforms of Prxs,Prx1 and Prx5,were silenced by RNA interference(RNAi).Following IR,intracellular reactive oxygen species(ROS)and apoptosis were measured using flow cytometry,the activities of catalase,superoxide dismutase and glutathione peroxidase were measured,and the radiosensjtjzjng effect of RNAi was observed.Tumor xenograft model was also used to examine the radiOsensitizing effect of RNAi in vivo.Results:Down-regulation of Prx1 and/or Prx5 by RNAi does not alter the activities of catalase, superoxide dismutase and glutathione peroxidase,but made human tumor cells more sensitive to IR-induced apoptosis both fn vitro and in vivO.When the two isoforms were decreased simultaneously,intracellular ROS and apoptosis significantly increased after IR.Conclusion:Silencing Prx1 and/or Prx5 by RNAi sensitizes human Eca-109 and TE-1 cells to IR, and the intracellular ROS accumulation may contribute to the radiosensitizing effect of the RNAi.

  19. Deletion of mtrC in Haemophilus ducreyi increases sensitivity to human antimicrobial peptides and activates the CpxRA regulon.

    Science.gov (United States)

    Rinker, Sherri D; Trombley, Michael P; Gu, Xiaoping; Fortney, Kate R; Bauer, Margaret E

    2011-06-01

    Haemophilus ducreyi resists killing by antimicrobial peptides encountered during human infection, including cathelicidin LL-37, α-defensins, and β-defensins. In this study, we examined the role of the proton motive force-dependent multiple transferable resistance (MTR) transporter in antimicrobial peptide resistance in H. ducreyi. We found a proton motive force-dependent effect on H. ducreyi's resistance to LL-37 and β-defensin HBD-3, but not α-defensin HNP-2. Deletion of the membrane fusion protein MtrC rendered H. ducreyi more sensitive to LL-37 and human β-defensins but had relatively little effect on α-defensin resistance. The mtrC mutant 35000HPmtrC exhibited phenotypic changes in outer membrane protein profiles, colony morphology, and serum sensitivity, which were restored to wild type by trans-complementation with mtrC. Similar phenotypes were reported in a cpxA mutant; activation of the two-component CpxRA regulator was confirmed by showing transcriptional effects on CpxRA-regulated genes in 35000HPmtrC. A cpxR mutant had wild-type levels of antimicrobial peptide resistance; a cpxA mutation had little effect on defensin resistance but led to increased sensitivity to LL-37. 35000HPmtrC was more sensitive than the cpxA mutant to LL-37, indicating that MTR contributed to LL-37 resistance independent of the CpxRA regulon. The CpxRA regulon did not affect proton motive force-dependent antimicrobial peptide resistance; however, 35000HPmtrC had lost proton motive force-dependent peptide resistance, suggesting that the MTR transporter promotes proton motive force-dependent resistance to LL-37 and human β-defensins. This is the first report of a β-defensin resistance mechanism in H. ducreyi and shows that LL-37 resistance in H. ducreyi is multifactorial.

  20. Increased CCL24/eotaxin-2 with postnatal ozone exposure in allergen-sensitized infant monkeys is not associated with recruitment of eosinophils to airway mucosa

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Debbie L.; Gerriets, Joan E. [California National Primate Research Center, UC Davis, Davis, CA 95616 (United States); Schelegle, Edward S.; Hyde, Dallas M. [California National Primate Research Center, UC Davis, Davis, CA 95616 (United States); Department of Anatomy, Physiology, and Cell Biology, UC Davis School of Veterinary Medicine, Davis, CA 95616 (United States); Miller, Lisa A., E-mail: lmiller@ucdavis.edu [California National Primate Research Center, UC Davis, Davis, CA 95616 (United States); Department of Anatomy, Physiology, and Cell Biology, UC Davis School of Veterinary Medicine, Davis, CA 95616 (United States)

    2011-12-15

    Epidemiology supports a causal link between air pollutant exposure and childhood asthma, but the mechanisms are unknown. We have previously reported that ozone exposure can alter the anatomic distribution of CD25+ lymphocytes in airways of allergen-sensitized infant rhesus monkeys. Here, we hypothesized that ozone may also affect eosinophil trafficking to allergen-sensitized infant airways. To test this hypothesis, we measured blood, lavage, and airway mucosa eosinophils in 3-month old monkeys following cyclical ozone and house dust mite (HDM) aerosol exposures. We also determined if eotaxin family members (CCL11, CCL24, CCL26) are associated with eosinophil location in response to exposures. In lavage, eosinophil numbers increased in animals exposed to ozone and/or HDM. Ozone + HDM animals showed significantly increased CCL24 and CCL26 protein in lavage, but the concentration of CCL11, CCL24, and CCL26 was independent of eosinophil number for all exposure groups. In airway mucosa, eosinophils increased with exposure to HDM alone; comparatively, ozone and ozone + HDM resulted in reduced eosinophils. CCL26 mRNA and immunofluorescence staining increased in airway mucosa of HDM alone animals and correlated with eosinophil volume. In ozone + HDM animal groups, CCL24 mRNA and immunofluorescence increased along with CCR3 mRNA, but did not correlate with airway mucosa eosinophils. Cumulatively, our data indicate that ozone exposure results in a profile of airway eosinophil migration that is distinct from HDM mediated pathways. CCL24 was found to be induced only by combined ozone and HDM exposure, however expression was not associated with the presence of eosinophils within the airway mucosa. -- Highlights: Black-Right-Pointing-Pointer Ozone can modulate the localization of eosinophils in infant allergic airways. Black-Right-Pointing-Pointer Expression of eotaxins within the lung is affected by ozone and allergen exposure. Black-Right-Pointing-Pointer CCL24 induction by

  1. Bmi1 gene silencing inhibits the proliferation and invasiveness of human hepatocellular carcinoma cells and increases their sensitivity to 5-fluorouracil.

    Science.gov (United States)

    Zhang, Rui; Xu, Lei-Bo; Yue, Xiu-Jing; Yu, Xian-Huan; Wang, Jie; Liu, Chao

    2013-03-01

    The Bmi1 gene has been reported to play important roles in cancer initiation and progression. The aim of this study was to investigate the effects of RNA interference (RNAi)-mediated silencing of Bmi1 gene expression on the proliferation and invasiveness of hepatocellular carcinoma (HCC) cells and on the efficacy of chemotherapy in HCC patients. The Bmi1 gene was silenced by Bmi1-siRNA (small interfering RNA) in the human HCC cell lines HepG2 and Bel-7402, and the gene expression levels were assayed by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting. The proliferation and migration of Bmi1-silenced tumor cells and their sensitivity to 5-FU treatment were determined by Cell Counting Kit-8 (CCK-8), transwell assays and 4',6-diamidino-2-phenylindole (DAPI) staining and flow cytometry, respectively. Bmi1-siRNA inhibited the Bmi1 expression at both the mRNA and protein levels in HCC cells. Proliferation and migration of HCC cells treated with Bmi1-siRNA was significantly lower compared to that of the control cells. Moreover, Bmi1 gene silencing increased the percentage of apoptotic cells treated by 5-FU and decreased the IC50 values of 5-FU to a greater extent. Downregulation of the Bmi1 gene by RNAi can inhibit the proliferation and invasivesness of HCC cells and increase their sensitivity to 5-FU treatment.

  2. Increased phytotoxic O3 dose accelerates autumn senescence in an O3-sensitive beech forest even under the present-level O3

    Science.gov (United States)

    Kitao, Mitsutoshi; Yasuda, Yukio; Kominami, Yuji; Yamanoi, Katsumi; Komatsu, Masabumi; Miyama, Takafumi; Mizoguchi, Yasuko; Kitaoka, Satoshi; Yazaki, Kenichi; Tobita, Hiroyuki; Yoshimura, Kenichi; Koike, Takayoshi; Izuta, Takeshi

    2016-09-01

    Ground-level ozone (O3) concentrations are expected to increase over the 21st century, especially in East Asia. However, the impact of O3 has not been directly assessed at the forest level in this region. We performed O3 flux-based risk assessments of carbon sequestration capacity in an old cool temperate deciduous forest, consisting of O3-sensitive Japanese beech (Fagus crenata), and in a warm temperate deciduous and evergreen forest dominated by O3-tolerant Konara oak (Quercus serrata) based on long-term CO2 flux observations. On the basis of a practical approach for a continuous estimation of canopy-level stomatal conductance (Gs), higher phytotoxic ozone dose above a threshold of 0 uptake (POD0) with higher Gs was observed in the beech forest than that in the oak forest. Light-saturated gross primary production, as a measure of carbon sequestration capacity of forest ecosystem, declined earlier in the late growth season with increasing POD0, suggesting an earlier autumn senescence, especially in the O3-sensitive beech forest, but not in the O3-tolerant oak forest.

  3. Stress-Induced Locomotor Sensitization to Amphetamine in Adult, but not in Adolescent Rats, Is Associated with Increased Expression of ΔFosB in the Nucleus Accumbens

    Science.gov (United States)

    Carneiro de Oliveira, Paulo E.; Leão, Rodrigo M.; Bianchi, Paula C.; Marin, Marcelo T.; Planeta, Cleopatra da Silva; Cruz, Fábio C.

    2016-01-01

    While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively) were restrained for 2 h once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p.) and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both the adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats. PMID:27672362

  4. Amp-PCR: combining a random unbiased Phi29-amplification with a specific real-time PCR, performed in one tube to increase PCR sensitivity.

    Directory of Open Access Journals (Sweden)

    Lena Erlandsson

    Full Text Available In clinical situations where a diagnostic real-time PCR assay is not sensitive enough, leading to low or falsely negative results, or where detection earlier in a disease progression would benefit the patient, an unbiased pre-amplification prior to the real-time PCR could be beneficial. In Amp-PCR, an unbiased random Phi29 pre-amplification is combined with a specific real-time PCR reaction. The two reactions are separated physically by a wax-layer (AmpliWax® and are run in sequel in the same sealed tube. Amp-PCR can increase the specific PCR signal at least 100×10(6-fold and make it possible to detect positive samples normally under the detection limit of the specific real-time PCR. The risk of contamination is eliminated and Amp-PCR could replace nested-PCR in situations where increased sensitivity is needed e.g. in routine PCR diagnostic analysis. We show Amp-PCR to work on clinical samples containing circular and linear viral dsDNA genomes, but can work well on DNA of any origin, both from non-cellular (virus and cellular sources (bacteria, archae, eukaryotes.

  5. Stress-induced locomotor sensitization to amphetamine in adult, but not in adolescent rats, is associated with increased expression of ΔFosB in the nucleus accumbens.

    Directory of Open Access Journals (Sweden)

    Paulo Eduardo Carneiro de Oliveira

    2016-09-01

    Full Text Available While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively were restrained for 2 hours once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p. and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats.

  6. 5-HTT deficiency affects neuroplasticity and increases stress sensitivity resulting in altered spatial learning performance in the Morris water maze but not in the Barnes maze.

    Directory of Open Access Journals (Sweden)

    Margherita M Karabeg

    Full Text Available The purpose of this study was to evaluate whether spatial hippocampus-dependent learning is affected by the serotonergic system and stress. Therefore, 5-HTT knockout (-/-, heterozygous (+/- and wildtype (+/+ mice were subjected to the Barnes maze (BM and the Morris water maze (WM, the latter being discussed as more aversive. Additionally, immediate early gene (IEG expression, hippocampal adult neurogenesis (aN, and blood plasma corticosterone were analyzed. While the performance of 5-HTT-/- mice in the BM was undistinguishable from both other genotypes, they performed worse in the WM. However, in the course of the repeated WM trials 5-HTT-/- mice advanced to wildtype level. The experience of a single trial of either the WM or the BM resulted in increased plasma corticosterone levels in all genotypes. After several trials 5-HTT-/- mice exhibited higher corticosterone concentrations compared with both other genotypes in both tests. Corticosterone levels were highest in 5-HTT-/- mice tested in the WM indicating greater aversiveness of the WM and a greater stress sensitivity of 5-HTT deficient mice. Quantitative immunohistochemistry in the hippocampus revealed increased cell counts positive for the IEG products cFos and Arc as well as for proliferation marker Ki67 and immature neuron marker NeuroD in 5-HTT-/- mice compared to 5-HTT+/+ mice, irrespective of the test. Most differences were found in the suprapyramidal blade of the dentate gyrus of the septal hippocampus. Ki67-immunohistochemistry revealed a genotype x environment interaction with 5-HTT genotype differences in naïve controls and WM experience exclusively yielding more Ki67-positive cells in 5-HTT+/+ mice. Moreover, in 5-HTT-/- mice we demonstrate that learning performance correlates with the extent of aN. Overall, higher baseline IEG expression and increased an in the hippocampus of 5-HTT-/- mice together with increased stress sensitivity may constitute the neurobiological correlate of

  7. 5-HTT deficiency affects neuroplasticity and increases stress sensitivity resulting in altered spatial learning performance in the Morris water maze but not in the Barnes maze.

    Science.gov (United States)

    Karabeg, Margherita M; Grauthoff, Sandra; Kollert, Sina Y; Weidner, Magdalena; Heiming, Rebecca S; Jansen, Friederike; Popp, Sandy; Kaiser, Sylvia; Lesch, Klaus-Peter; Sachser, Norbert; Schmitt, Angelika G; Lewejohann, Lars

    2013-01-01

    The purpose of this study was to evaluate whether spatial hippocampus-dependent learning is affected by the serotonergic system and stress. Therefore, 5-HTT knockout (-/-), heterozygous (+/-) and wildtype (+/+) mice were subjected to the Barnes maze (BM) and the Morris water maze (WM), the latter being discussed as more aversive. Additionally, immediate early gene (IEG) expression, hippocampal adult neurogenesis (aN), and blood plasma corticosterone were analyzed. While the performance of 5-HTT-/- mice in the BM was undistinguishable from both other genotypes, they performed worse in the WM. However, in the course of the repeated WM trials 5-HTT-/- mice advanced to wildtype level. The experience of a single trial of either the WM or the BM resulted in increased plasma corticosterone levels in all genotypes. After several trials 5-HTT-/- mice exhibited higher corticosterone concentrations compared with both other genotypes in both tests. Corticosterone levels were highest in 5-HTT-/- mice tested in the WM indicating greater aversiveness of the WM and a greater stress sensitivity of 5-HTT deficient mice. Quantitative immunohistochemistry in the hippocampus revealed increased cell counts positive for the IEG products cFos and Arc as well as for proliferation marker Ki67 and immature neuron marker NeuroD in 5-HTT-/- mice compared to 5-HTT+/+ mice, irrespective of the test. Most differences were found in the suprapyramidal blade of the dentate gyrus of the septal hippocampus. Ki67-immunohistochemistry revealed a genotype x environment interaction with 5-HTT genotype differences in naïve controls and WM experience exclusively yielding more Ki67-positive cells in 5-HTT+/+ mice. Moreover, in 5-HTT-/- mice we demonstrate that learning performance correlates with the extent of aN. Overall, higher baseline IEG expression and increased an in the hippocampus of 5-HTT-/- mice together with increased stress sensitivity may constitute the neurobiological correlate of raised

  8. Aqueous exposure to 4-nonylphenol and 17β-estradiol increases stress sensitivity and disrupts ion regulatory ability of juvenile atlantic salmon

    Science.gov (United States)

    Lerner, Darrren T.; Bjornsson, Bjorn Thrandur; McCormick, Stephen D.

    2007-01-01

    Population declines of wild Atlantic salmon have been attributed to an array of anthropogenic disturbances, including dams, commercial and recreational fishing, habitat loss, and pollution. Environmental contaminants in particular, can act as environmental stressors on fish, typically causing disruption of ion homeostasis due to their close association with the aquatic environment. To examine the effects of the xenoestrogen 4-nonylphenol (NP) or 17β-estradiol (E2) on stress sensitivity and ion regulation, we exposed juvenile Atlantic salmon continuously for 21 d to either 10 or 100 μg/L NP (NP-L or NP-H), 2 μg/L E2 (positive control), or vehicle control during the parr-smolt transformation in April. After treatment, fish were sampled in freshwater (FW), transferred to 30‰ seawater (SW) for 24 h, or subjected to a handling stress. Estradiol and NP-H increased plasma vitellogenin in males and females, and E2 increased gonadosomatic index only in males. In FW, E2 reduced sodium potassium–activated adenosine triphosphatase activity as well as plasma levels of growth hormone, insulin-like growth factor I, and triiodothyronine. Both E2 and NP-H reduced plasma sodium in FW and increased plasma chloride in SW. Plasma Cortisol levels pre- and poststressor were significantly elevated by all treatments relative to controls, but only E2 increased plasma glucose before and after the stressor. These results indicate that exposure of anadromous salmonids to environmental estrogens heightens sensitivity to external stressors, impairs ion regulation in both FW and SW, and disrupts endocrine pathways critical for smolt development.

  9. A nicardipine-sensitive Ca2+ entry contributes to the hypotonicity-induced increase in [Ca2+]i of principal cells in rat cortical collecting duct.

    Science.gov (United States)

    Komagiri, You; Nakamura, Kazuyoshi; Kubokawa, Manabu

    2011-01-01

    We examined the mechanisms involved in the [Ca(2+)](i) response to the extracellular hypotonicity in the principal cells of freshly isolated rat cortical collecting duct (CCD), using Fura-2/AM fluorescence imaging. Reduction of extracellular osmolality from 305 (control) to 195 mosmol/kgH(2)O (hypotonic) evoked transient increase in [Ca(2+)](i) of principal cells of rat CCDs. The [Ca(2+)](i) increase was markedly attenuated by the removal of extracellular Ca(2+)(.) The application of a P(2) purinoceptor antagonist, suramin failed to inhibit the hypotonicity-induced [Ca(2+)](i) increase. The [Ca(2+)](i) increase in response to extracellular hypotonicity was not influenced by application of Gd(3+) and ruthenium red. On the other hand, a voltage-gated Ca(2+) channel inhibitor, nicardipine, significantly reduced the peak amplitude of [Ca(2+)](i) increase in the principal cells. In order to assess Ca(2+) entry during the hypotonic stimulation, we measured the quenching of Fura-2 fluorescence intensity by Mn(2+). The hypotonic stimulation enhanced quenching of Fura-2 fluorescence by Mn(2+), indicating that a Ca(2+)-permeable pathway was activated by the hypotonicity. The hypotonicity-mediated enhancement of Mn(2+) quenching was significantly inhibited by nicardipine. These results strongly suggested that a nicardipine-sensitive Ca(2+) entry pathway would contribute to the mechanisms underlying the hypotonicity-induced [Ca(2+)](i) elevation of principal cells in rat CCD.

  10. S-腺苷甲硫氨酸改善OLETF大鼠胰岛素敏感性%S-adenosyl-L-methionine increases insulin sensitivity of OLETF rats

    Institute of Scientific and Technical Information of China (English)

    金成吉; 王晓梅; 李湘; 冯海娟; 母义明

    2011-01-01

    Objective To investigate the effective of S-adenosyl-L-methionine (SAMe) on skeletal muscle mitochondrial DNA density and insulin sensitivity of Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods SAMe[ 15 mg/( kg · d)] or placebo was administered intraperitoneally for 6-week-old OLETF rats. Food intake,body weight and skeletal muscle mitochondrial DNA density were determined. Insulin sensitivity was evaluated by euglycemic-hyperinsulinemic clamp test. Results SAMe treatment significantly inhibited food intake and reduced body weight gain as well as increased skeletal muscle mitochondrial DNA density and whole body insulin sensitivity in OLETF rats compared with their controls. Furthermore, skeletal muscle mitochondrial DNA density correlated with insulin body weight ( γ= 0. 696, P < 0. 05 ). Conclusion SAMe treatment increased mitochondrial DNA density in skeletal muscle that prevented body weight gain and improved whole body insulin sensitivity in OLETF rats.%目的 观察S-腺苷甲硫氨酸对肥胖的2型糖尿病模型OLETF鼠骨骼肌mtDNA量和胰岛素敏感性的影响.方法 每日给大鼠腹腔内注射S-腺苷甲硫氨酸(15 mg/kg)或安慰剂,测定食物摄入量、体质最及骨骼肌mtDNA量.行静脉葡萄糖耐量试验和正葡萄糖高胰岛素钳夹实验评价胰岛素敏感性.结果 S-腺苷甲硫氨酸治疗后OLETF大鼠进食量减少,体质量增加幅度下降,骨骼肌mtDNA量增加,葡萄糖输注速度增加,骨骼肌mtDNA量与体质量呈负相关(γ=0.696,P<0.05).结论 S-腺苷甲硫氨酸可以改善OLETF鼠胰岛素敏感性,抑制体质量增加,增加骨骼肌mtDNA量.

  11. Increased sensitivity to testicular toxicity of transplacental benzo[a]pyrene exposure in male glutamate cysteine ligase modifier subunit knockout (Gclm-/-) mice.

    Science.gov (United States)

    Nakamura, Brooke N; Mohar, Isaac; Lawson, Gregory W; Cortés, Mabel M; Hoang, Yvonne D; Ortiz, Laura; Patel, Reshma; Rau, Bogdan A; McConnachie, Lisa A; Kavanagh, Terrance J; Luderer, Ulrike

    2012-03-01

    Polycyclic aromatic hydrocarbons (PAHs), like benzo[a]pyrene (BaP), are ubiquitous environmental pollutants formed by the incomplete combustion of organic materials. The tripeptide glutathione (GSH) is a major antioxidant and is important in detoxification of PAH metabolites. Mice null for the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH concentrations. We investigated the effects of Gclm deletion alone on male fertility and spermatogenesis and its effect on the sensitivity of male embryos to the transplacental testicular toxicity of BaP. Gclm-/- males had dramatically decreased testicular and epididymal GCL enzymatic activity and total GSH concentrations compared with Gclm+/+ littermates. Ratios of reduced to oxidized GSH were significantly increased in Gclm-/- testes. GSH reductase enzymatic activity was increased in Gclm-/- epididymides. We observed no changes in fertility, testicular weights, testicular sperm head counts, or testicular histology and subtle changes in cauda epididymal sperm counts, motility, and morphology in Gclm-/- compared with Gclm+/+ males. Prenatal exposure to BaP from gestational day 7 to 16 was dose dependently associated with significantly decreased testicular and epididymal weights, testicular and epididymal sperm counts, and with vacuolated seminiferous tubules at 10 weeks of age. Gclm-/- males exposed prenatally to BaP had greater decreases in testicular weights, testicular sperm head counts, epididymal sperm counts, and epididymal sperm motility than Gclm+/+ littermates. These results show no effects of Gclm deletion alone on male fertility and testicular spermatogenesis and subtle epididymal effects but support increased sensitivity of Gclm-/- males to the transplacental testicular toxicity of BaP.

  12. Using a 3% Proton Density Fat Fraction as a Cut-off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results from Histopathology Analysis.

    Science.gov (United States)

    Nasr, Patrik; Forsgren, Mikael F; Ignatova, Simone; Dahlström, Nils; Cedersund, Gunnar; Leinhard, Olof Dahlqvist; Norén, Bengt; Ekstedt, Mattias; Lundberg, Peter; Kechagias, Stergios

    2017-03-09

    It is possible to estimate hepatic triglyceride content by calculating the proton density fat fraction (PDFF), using proton magnetic resonance spectroscopy ((1)H-MRS), instead of collecting and analyzing liver biopsies to detect steatosis. However, the current PDFF cut-off value (5%) used to define steatosis by magnetic resonance was derived from studies that did not use histopathology as the reference standard. We performed a prospective study to determine the accuracy of (1)H-MRS PDFF in measurement of steatosis using histopathology analysis as the standard. We collected clinical, serologic, (1)H-MRS PDFF, and liver biopsy data from 94 adult patients with increased levels of liver enzymes (6 months or more) referred to the Department of Gastroenterology and Hepatology at Linköping University Hospital in Sweden from 2007 through 2014. Steatosis was graded using the conventional histopathology method and fat content was quantified in biopsy samples using stereological point counts (SPCs). We correlated (1)H-MRS PDFF findings with SPCs (r = 0.92; P <.001). (1)H-MRS PDFF results correlated with histopathology results (ρ = 0.87; P <.001), and SPCs correlated with histopathology results (ρ = 0.88; P <.001). All 25 subjects with PDFF values of 5.0% or more had steatosis based on histopathology findings (100% specificity for PDFF). However, of 69 subjects with PDFF values below 5.0% (negative result), 22 were determined to have steatosis based on histopathology findings (53% sensitivity for PDFF). Reducing the PDFF cut-off value to 3.0% identified patients with steatosis with 100% specificity and 79% sensitivity; a PDFF cut-off value of 2.0% identified patients with steatosis with 94% specificity and 87% sensitivity. These findings might be used to improve non-invasive detection of steatosis.

  13. Reduced TRMU expression increases the sensitivity of hair-cell-like HEI-OC-1 cells to neomycin damage in vitro

    Science.gov (United States)

    He, Zuhong; Sun, Shan; Waqas, Muhammad; Zhang, Xiaoli; Qian, Fuping; Cheng, Cheng; Zhang, Mingshu; Zhang, Shasha; Wang, Yongming; Tang, Mingliang; Li, Huawei; Chai, Renjie

    2016-01-01

    Aminoglycosides are ototoxic to the cochlear hair cells, and mitochondrial dysfunction is one of the major mechanisms behind ototoxic drug-induced hair cell death. TRMU (tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase) is a mitochondrial protein that participates in mitochondrial tRNA modifications, but the role of TRMU in aminoglycoside-induced ototoxicity remains to be elucidated. In this study, we took advantage of the HEI-OC-1 cell line to investigate the role of TRMU in aminoglycoside-induced cell death. We found that TRMU is expressed in both hair cells and HEI-OC-1 cells, and its expression is significantly decreased after 24 h neomycin treatment. We then downregulated TRMU expression with siRNA and found that cell death and apoptosis were significantly increased after neomycin injury. Furthermore, when we down-regulated TRMU expression, we observed significantly increased mitochondrial dysfunction and increased levels of reactive oxygen species (ROS) after neomycin injury, suggesting that TRMU regulates mitochondrial function and ROS levels. Lastly, the antioxidant N-acetylcysteine rescued the mitochondrial dysfunction and cell apoptosis that was induced by TRMU downregulation, suggesting that ROS accumulation contributed to the increased aminoglycosides sensitivity of HEI-OC-1 cells after TRMU downregulation. This study provides evidence that TRMU might be a new therapeutic target for the prevention of aminoglycoside-induced hair cell death. PMID:27405449

  14. Retraction Statement: 'MicroRNA-218 increases cellular sensitivity to Rapamycin via targeting Rictor in cervical cancer' by Li J, Wang J, Wang Y, Qiu H.

    Science.gov (United States)

    2017-02-01

    The above article from APMIS, published online on 24 April 2015 in Wiley Online Library (wileyonlinelibrary.com) and in Volume 123, pp. 562-570, has been retracted by agreement between the authors, the journal Editors in Chief, Professors Bodil Norrild, Ben Vainer and Elisabeth Ralfkiaer, and John Wiley & Sons Ltd. The article has been retracted due to errors in the reported results. In this study, the authors used HeLa and SiHa cell lines to investigate the biological roles of miR-218. However, subsequently it emerged that the two cell lines were contaminated in the laboratory by other unknown cell lines. When repeating the experiments, it was found that the functions of miR-218 were not as significant as had been previously reported, especially its effects on rapamycin sensitivity. Reference Li J, Li X, Wang J, Wang Y, Qiu H. MicroRNA-218 increases cellular sensitivity to Rapamycin via targeting Rictor in cervical cancer. APMIS 2015; 123:562-570. doi: 10.1111/apm.12387.

  15. Dengue NS1 and prM antibodies increase the sensitivity of acute dengue diagnosis test and differentiate from Japanese encephalitis infection.

    Science.gov (United States)

    Gowri Sankar, S; Balaji, T; Venkatasubramani, K; Thenmozhi, V; Dhananjeyan, K J; Paramasivan, R; Tyagi, B K; John Vennison, S

    2014-05-01

    Accurate and early diagnosis of dengue infection is essential for dengue case management. In outbreak conditions, it is essential to include two different tests to diagnose dengue and the choice depends on the number of days after the onset of illness in which the sample is collected. During the laboratory diagnosis of dengue in late acute and convalescent phase by MAC-ELISA, it is necessary to rule out possible cross reactions of closely related flavivirus, such as Japanese encephalitis virus which is commonly co-circulating. In the present investigation, the usefulness of dengue virus NS1 and prM antibodies in diagnosing and differentiating dengue from Japanese encephalitis infection was assessed using samples collected during out-breaks. It was shown here that, detection of antibodies against dengue NS1 and prM proteins increases the sensitivity of dengue diagnosis until 15days. Moreover, detection of antibodies against both proteins was able to differentiate dengue from Japanese encephalitis infection.

  16. Hormone resistance in two MCF-7 breast cancer cell lines is associated with reduced mTOR signaling, decreased glycolysis and increased sensitivity to cytotoxic drugs

    Directory of Open Access Journals (Sweden)

    Euphemia Yee Leung

    2014-09-01

    Full Text Available The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume and resistance to mTOR inhibition. Here we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, docetaxel and hydrogen peroxide. The mechanisms underlying these changes have not yet been characterized but may include a shift from glycolysis to mitochondrial respiration. If this phenotype is found in clinical hormone-resistant breast cancers, conventional cytotoxic therapy may be a preferred option for treatment.

  17. Increase in efficiency of dye-sensitized solar cells by porous TiO2 layer modification with gadolinium-containing thin layer

    Institute of Scientific and Technical Information of China (English)

    Maciej Zalas; Mariusz Walkowiak; Grzegorz Schroeder

    2011-01-01

    Modified with gadolinium-containing layer,nanoporous titania electrode and its application in dye-sensitized solar cells were reported.The electrode prepared was characterized with UV-Vis and X-ray diffraction (XRD) techniques.The amount of gadolinium was measured with inductively coupled plasma-optical emission spectrometry (ICP-OES) experiments.The modified electrode showed reduced N3 dye adsorption ability,but increased light conversion efficiency in comparison with the non-modified electrode.The overall conversion efficiencies,determined under 400 W/m2 irradiation with tungsten- halogen lamp at room temperature,were 0.55% for non-modified and 0.74% for modified electrodes.

  18. Anti-epidermal growth factor receptor siRNA carried by chitosan-transacylated lipid nanocapsules increases sensitivity of glioblastoma cells to temozolomide

    Directory of Open Access Journals (Sweden)

    Messaoudi K

    2014-03-01

    Full Text Available Khaled Messaoudi,1 Patrick Saulnier,1 Kim Boesen,1 Jean-Pierre Benoit,1,2 Frederic Lagarce1,21L'Université Nantes Angers Le Mans, INSERM U1066, Micro et nanomédecines biomimétiques, Angers, France; 2Pharmacy Department, Angers University Hospital, Angers, FranceAbstract: Epidermal growth factor receptor (EGFR is a crucial protein that plays an important role in the maintenance and development of glioblastomas. The silencing or knockdown of EGFR is possible by administering a small interfering ribonucleic acid (siRNA. Lipid nanocapsules (LNCs covered by chitosan were developed in our laboratory by a transacylation process. The resulting nanocapsules have a positive zeta potential that enables electrostatic interactions with the negatively-charged siRNA. Prior to transfection, the cytotoxicity of the nanocapsules by (3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium (MTS test was performed on the U87MG cell line to determine non-toxic levels of the LNCs to avoid cell mortality. Treatment of the U87MG cells with the chitosan-transacylated LNCs/anti-EGFR siRNA complex resulted in a reduction of EGFR expression by 51.95%±6.03% (P≤0.05 after 96 hours of incubation. It also increased the cellular sensitivity to temozolomide in comparison to untreated cells with siRNA. The largest increase in mortality was 62.55%±3.55% (P<0.05. This successful knockdown provides proof for the concept of surface grafting of siRNA onto LNCs to modify cell sensitivity to temozolomide. The method could be implemented in future clinical models regarding the experimental treatment of glioblastoma cancer.Keywords: EGFR, glioblastoma, siRNA, lipid nanocapsules, chitosan, temozolomide

  19. Abrogated thioredoxin system causes increased sensitivity to TNF-α-induced apoptosis via enrichment of p-ERK 1/2 in the nucleus.

    Science.gov (United States)

    Yoo, Min-Hyuk; Carlson, Bradley A; Gladyshev, Vadim N; Hatfield, Dolph L

    2013-01-01

    Thioredoxin (Trx) and thioredoxin reductase 1 (TR1) are among the major redox regulators in mammalian cells and have a wide variety of roles, including removal of intracellular reactive oxygen species (ROS) and prevention of cell death. Tumor necrosis factor-α (TNF-α) induces cancer cell death. Although ROS have been proposed to participate in this process, the role of the thioredoxin system in TNF-α stimulated cell death remains unclear. We investigated the possibility that the thioredoxin system protects against TNF-α-induced cancer cell death by examining whether TR1/Trx1 status controls TNF-α-induced apoptosis in EMT6 murine breast cancer cells. TR1-deficient cells were more sensitive to TNF-α than control cells. Increased sensitivity to TNF-α was most pronounced in Trx1-deficient cells. TNF-α-induced nuclear localization of phosphorylated ERK 1/2 (p-ERK 1/2) correlated with increased apoptosis in TR1- and Trx1-deficient cells, suggesting a pro-apoptotic role for nuclear p-ERK 1/2 in TNF-α-induced apoptosis. In addition, phosphoinositide 3-kinase (PI3K) inhibition dramatically reduced TNF-α-stimulated apoptosis and nuclear localization of p-ERK 1/2. In contrast, inhibition of ROS, MEK, JNK, or p38 did not significantly alter p-ERK 1/2 localization or apoptosis in TR1- and Trx1-deficient cells compared to control cells. Further, NF-κB p65 localization was not changed in TR1- and Trx1-deficient cells in response to TNF-α relative to control cells. Our data suggest that the thioredoxin system plays a critical role in protecting against TNF-α-induced apoptosis by regulating the levels of nuclear p-ERK 1/2 in a PI3K-dependent manner.

  20. Interference with Activator Protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation- sensitivity in breast cancer cells

    LENUS (Irish Health Repository)

    Thewes, Verena

    2010-05-11

    Abstract Background Activator Protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2α and AP-2γ is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo- or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms. Methods We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant. Results We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo- and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo- and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network. Conclusions Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo- and radiation-resistance of tumor cells by impairing the

  1. Increased charge transfer of PVDF-HFP based electrolyte by addition of graphite nanofiber and its application in dye-sensitized solar cells

    Science.gov (United States)

    Zhao, Xing Guan; Jin, En Mei; Gu, Hal-Bon

    2013-12-01

    The PEO and PVDF-HFP mixtures were used as polymer electrolytes in solid-state dye-sensitized solar cells (DSSCs). Correlation between the ionic conductivity and cell performance by varying the composition of polymer electrolytes was investigated to elucidate the importance of the ionic conductivity in determining the charge transfer and energy conversion efficiency of solid-state DSSCs. In this work, for increasing the ionic conductivity and charge transfer, GNF was added to the polymer electrolyte. The ionic conductivity of polymer electrolyte containing GNF (0.005 g) is 8.67 × 10-4 S cm-1 and pristine polymer electrolyte is 3.81 × 10-4 S cm-1. The charge transfer of GNF (0.005 g) added DSSCs is faster than the other samples, the electron transport time is 1.53 ms and electron life time is 27.20 ms. The increase of current density with the polymer electrolyte containing GNF (0.005 g) can be possibly attributed to the direct contact between dye/TiO2 and I/I3- that will improve the charge transportation. The highest energy conversion efficiency of 4.60% is obtained for polymer electrolyte containing GNF (0.005 g).

  2. Increased charge transfer of PVDF-HFP based electrolyte by addition of graphite nanofiber and its application in dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Xing Guan; Jin, En Mei; Gu, Hal-Bon, E-mail: hbgu@chonnam.ac.kr

    2013-12-15

    The PEO and PVDF-HFP mixtures were used as polymer electrolytes in solid-state dye-sensitized solar cells (DSSCs). Correlation between the ionic conductivity and cell performance by varying the composition of polymer electrolytes was investigated to elucidate the importance of the ionic conductivity in determining the charge transfer and energy conversion efficiency of solid-state DSSCs. In this work, for increasing the ionic conductivity and charge transfer, GNF was added to the polymer electrolyte. The ionic conductivity of polymer electrolyte containing GNF (0.005 g) is 8.67 × 10{sup −4} S cm{sup −1} and pristine polymer electrolyte is 3.81 × 10{sup −4} S cm{sup −1}. The charge transfer of GNF (0.005 g) added DSSCs is faster than the other samples, the electron transport time is 1.53 ms and electron life time is 27.20 ms. The increase of current density with the polymer electrolyte containing GNF (0.005 g) can be possibly attributed to the direct contact between dye/TiO{sub 2} and I{sup −}/I{sub 3}{sup −} that will improve the charge transportation. The highest energy conversion efficiency of 4.60% is obtained for polymer electrolyte containing GNF (0.005 g)

  3. MicroRNA-149 Increases the Sensitivity of Colorectal Cancer Cells to 5-Fluorouracil by Targeting Forkhead Box Transcription Factor FOXM1

    Directory of Open Access Journals (Sweden)

    Xiaobei Liu

    2016-07-01

    Full Text Available Background/Aims: Previously, we have shown that microRNA (miR-149 suppresses the migration and invasion of colorectal cancer (CRC cells by targeting forkhead box transcription factor (FOXM1. However, the roles of miR-149 in the chemoresistance of CRC cells to 5-Fluorouracil (5-FU is unclear. The aim of this study is to investigate whether miR-149 targets FOXM1 to regulate the 5-FU resistance of CRC. Methods: The qRT-PCR assay was performed to detect the expression of miR-149 in 5-FU-resistant CRC cells (HCT-8/5-FU and LoVo/5-FU and their parental CRC cells (HCT-8 and LoVo. Also, the effects of miR-149 expression on the sensitivity of CRC cells to 5-FU were determined by gain- and loss-of-function assays. Finally, whether miR-149 regulates the 5-FU resistance of CRC cells by targeting the mammalian Forkhead Box M1 (FOXM1 was investigated. Results: The expression of miR-149 was significantly downregulated in 5-FU-resistant CRC cells in comparison with their parental CRC cells. Re-expression of miR-149 could enhance the 5-FU sensitivity of 5-FU-resistant CRC cells by increasing 5-FU-inducing apoptosis, while downregulation of miR-149 could decrease the 5-FU sensitivity of parental CRC cells by decreasing 5-FU-inducing apoptosis. In addition, the luciferase assay indicated that miR-149 could bind to the 3'-UTR sequence of FOXM1 mRNA. The silencing of FOXM1 could mimic the effect of miR-149 upregulation on the 5-FU resistance of 5-FU-resistant CRC cells. Furthermore, the expression of miR-149 in the 5-FU-responding CRC tissues was significantly higher than that in the non-responding tissues and inversely correlated with FOXM1 mRNA level. Conclusions: MiR-149 reverses the resistance of CRC cells to 5-FU by directly targeting FOXM1. Thus, targeting miR-149/FOXM1 signaling will be a potential strategy in the treatment of 5-FU-chemoresistant CRC.

  4. Arabidopsis AtDjA3 null mutant shows increased sensitivity to abscisic acid, salt, and osmotic stress in germination and postgermination stages

    Directory of Open Access Journals (Sweden)

    Silvia eSalas-Muñoz

    2016-02-01

    Full Text Available DnaJ proteins are essential co-chaperones involved in abiotic and biotic stress responses. Arabidopsis AtDjA3 gene encodes a molecular co-chaperone of 420 amino acids, which belongs to the J-protein family. In this study, we report the functional characterization of the AtDjA3 gene using the Arabidopsis knockout line designated j3 and the 35S::AtDjA3 overexpression lines. Loss of AtDjA3 function was associated with small seed production. In fact, j3 mutant seeds showed a reduction of 24% in seed weight compared to Col-0 seeds. Expression analysis showed that the AtDjA3 gene was modulated in response to NaCl, glucose, and abscisic acid. The j3 line had increased sensitivity to NaCl and glucose treatments in the germination and cotyledon development in comparison to parental Col-0. Furthermore, the j3 mutant line exhibited higher abscisic acid sensitivity in comparison to parental Col-0 and 35S::AtDjA3 overexpression lines. In addition, we examined the expression of ABI3 gene, which is a central regulator in ABA signalling, in j3 mutant and 35S::AtDjA3 overexpression lines. Under 5 μM ABA treatment at 24 h, j3 mutant seedlings displayed higher ABI3 expression, whereas in 35S::AtDjA3 overexpression lines, ABI3 gene expression was repressed. Taken together, these results demonstrate that the AtDjA3 gene is involved in seed development and abiotic stress tolerance.

  5. The background of mitochondrial DNA haplogroup J increases the sensitivity of Leber's hereditary optic neuropathy cells to 2,5-hexanedione toxicity.

    Directory of Open Access Journals (Sweden)

    Anna Ghelli

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally inherited blinding disease due to mitochondrial DNA (mtDNA point mutations in complex I subunit genes, whose incomplete penetrance has been attributed to both genetic and environmental factors. Indeed, the mtDNA background defined as haplogroup J is known to increase the penetrance of the 11778/ND4 and 14484/ND6 mutations. Recently it was also documented that the professional exposure to n-hexane might act as an exogenous trigger for LHON. Therefore, we here investigate the effect of the n-hexane neurotoxic metabolite 2,5-hexanedione (2,5-HD on cell viability and mitochondrial function of different cell models (cybrids and fibroblasts carrying the LHON mutations on different mtDNA haplogroups. The viability of control and LHON cybrids and fibroblasts, whose mtDNAs were completely sequenced, was assessed using the MTT assay. Mitochondrial ATP synthesis rate driven by complex I substrates was determined with the luciferine/luciferase method. Incubation with 2,5-HD caused the maximal loss of viability in control and LHON cells. The toxic effect of this compound was similar in control cells irrespective of the mtDNA background. On the contrary, sensitivity to 2,5-HD induced cell death was greatly increased in LHON cells carrying the 11778/ND4 or the 14484/ND6 mutation on haplogroup J, whereas the 11778/ND4 mutation in association with haplogroups U and H significantly improved cell survival. The 11778/ND4 mutation on haplogroup U was also more resistant to inhibition of complex I dependent ATP synthesis by 2,5-HD. In conclusion, this study shows that mtDNA haplogroups modulate the response of LHON cells to 2,5-HD. In particular, haplogroup J makes cells more sensitive to its toxic effect. This is the first evidence that an mtDNA background plays a role by interacting with an environmental factor and that 2,5-HD may be a risk element for visual loss in LHON. This proof of principle has broad

  6. MicroRNA-133b targets glutathione S-transferase π expression to increase ovarian cancer cell sensitivity to chemotherapy drugs

    Directory of Open Access Journals (Sweden)

    Chen S

    2015-09-01

    Full Text Available Shuo Chen,1 Jin-Wen Jiao,2 Kai-Xuan Sun,1 Zhi-Hong Zong,3 Yang Zhao1 1Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Gynecology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, People’s Republic of China Background: Accumulating studies reveal that aberrant microRNA (miRNA expression can affect the development of chemotherapy drug resistance by modulating the expression of relevant target proteins. The aim of this study was to investigate the role of miR-133b in the development of drug resistance in ovarian cancer cells. Methods: We examined the levels of miR-133b expression in ovarian carcinoma tissues and the human ovarian carcinoma cell lines (A2780, A2780/DDP and A2780/Taxol, respectively. We determined the cell viability of these cell lines treated with cisplatin or paclitaxel in the presence or absence of miR-133b or anti-miR-133b transfection using the MTT assay. Reverse transcription polymerase chain reaction and Western blotting were used to assess the mRNA and protein expression levels of two drug-resistance-related genes: glutathione S-transferase (GST-π and multidrug resistance protein 1 (MDR1. The dual-luciferase reporter assay was used to detect the promoter activity of GST-π in the presence and absence of miR-133b. Results: The expression of miR-133b was significantly lower in primary resistant ovarian carcinomas than in the chemotherapy-sensitive carcinomas (P<0.05, and the same results were found in primary resistant ovarian cell lines (A2780/Taxol and A2780/DDP compared to the chemotherapy-sensitive cell line (A2780; P<0.05. Following miR-133b transfection, four cell lines showed increased sensitivity to paclitaxel and cisplatin, while anti-miR-133b transfection

  7. Activation and increase of radio-sensitive CD11b+ recruited Kupffer cells/macrophages in diet-induced steatohepatitis in FGF5 deficient mice

    Science.gov (United States)

    Nakashima, Hiroyuki; Nakashima, Masahiro; Kinoshita, Manabu; Ikarashi, Masami; Miyazaki, Hiromi; Hanaka, Hiromi; Imaki, Junko; Seki, Shuhji

    2016-01-01

    We have recently reported that Kupffer cells consist of two subsets, radio-resistant resident CD68+ Kupffer cells and radio-sensitive recruited CD11b+ Kupffer cells/macrophages (Mφs). Non-alcoholic steatohepatitis (NASH) is characterized not only by hepatic steatosis but also chronic inflammation and fibrosis. In the present study, we investigated the immunological mechanism of diet-induced steatohepatitis in fibroblast growth factor 5 (FGF5) deficient mice. After consumption of a high fat diet (HFD) for 8 weeks, FGF5 null mice developed severe steatohepatitis and fibrosis resembling human NASH. F4/80+ Mφs which were both CD11b and CD68 positive accumulated in the liver. The production of TNF and FasL indicated that they are the pivotal effectors in this hepatitis. The weak phagocytic activity and lack of CRIg mRNA suggested that they were recruited Mφs. Intermittent exposure to 1 Gy irradiation markedly decreased these Mφs and dramatically inhibited liver inflammation without attenuating steatosis. However, depletion of the resident subset by clodronate liposome (c-lipo) treatment increased the Mφs and tended to exacerbate disease progression. Recruited CD11b+ CD68+ Kupffer cells/Mφs may play an essential role in steatohepatitis and fibrosis in FGF5 null mice fed with a HFD. Recruitment and activation of bone marrow derived Mφs is the key factor to develop steatohepatitis from simple steatosis. PMID:27708340

  8. Effect of ageing on the passive and active tension and pharmacodynamic characteristics of rat coronary arteries: age-dependent increase in sensitivity to 5-HT and K+.

    Science.gov (United States)

    Sheykhzade, Majid; Simonsen, Anja Hviid; Boonen, Harrie C M; Outzen, Emilie M; Nyborg, Niels C Berg

    2012-01-01

    The influence of ageing on the passive and active tension and pharmacodynamic characteristics of intramural coronary arteries from 3-month-old and 2-year-old male Wistar rats was investigated using an isometric myograph. The passive vessel wall tension measured in Ca(2+)-free physiological salt solution at L(0) was significantly greater in arteries from old rats (1.46 ± 0.10 Nm(-1), n = 7) than in young rats (1.13 ± 0.13 Nm(-1), n = 6). However, the maximal active tension at L(0) was similar. The spontaneous myogenic tone was increased by age and the vasorelaxation induced by extracellular K(+) was significantly higher in coronary arteries of old rats. The sensitivity (pD(2)) to 5-HT was significantly higher in arteries from old (6.43 ± 0.11, n = 22) than from young rats (6.16 ± 0.08, n = 29). Ketanserin induced a concentration-dependent rightward shift of the 5-HT concentration-response curve in arteries from both young and old rats. The slopes of the regression lines of the Schild plots were not significantly different from unity and the estimated pK(B) values for ketanserin were similar. In conclusion, ageing is associated with changes in passive mechanical characteristics as well as changes in pharmacological properties in rat coronary small arteries.

  9. Preexposure to Olive Oil Polyphenols Extract Increases Oxidative Load and Improves Liver Mass Restoration after Hepatectomy in Mice via Stress-Sensitive Genes

    Directory of Open Access Journals (Sweden)

    Jelena Marinić

    2016-01-01

    Full Text Available Polyphenols can act as oxidants in some conditions, inducing redox-sensitive genes. We investigated the effect of preexposure to the olive oil polyphenols extract (PFE on time-dependent changes in the hepatic oxidative state in a model of liver regeneration—a process in which oxidative stress associated with the metabolic overload accounts for the early events that contribute to the onset of liver self-repair. Liver regeneration was induced by one-third hepatectomy in mice. Prior to hepatectomy, mice were intraperitoneally given either PFE (50 mg/kg body weight or saline for seven consecutive days, while respective controls received vehicle alone. Redox state-regulating enzymes and thiol proteins along with the mRNA levels of Nrf2 gene and its targets γ-glutamylcysteine synthetase and heme oxygenase-1 were determined at different time intervals after hepatectomy. The liver mass restoration was calculated to assess hepatic regeneration. The resulting data demonstrate the effectiveness of preexposure to PFE in stimulating liver regeneration in a model of a small tissue loss which may be ascribed to the transient increase in oxidant load during the first hours after hepatectomy and associated induction of stress response gene-profiles under the control of Nrf2.

  10. The Dual Amylin- and Calcitonin-Receptor Agonist KBP-042 Increases Insulin Sensitivity and Induces Weight Loss in Rats with Obesity

    DEFF Research Database (Denmark)

    Hjuler, Sara Toftegaard; Gydesen, Sofie; Andreassen, Kim Vietz

    2016-01-01

    Objective: In this study, KBP-042, a dual amylin- and calcitonin-receptor agonist, was investigated as a treatment of obesity and insulin resistance in five different doses (0.625 μg/kg-10 μg/kg) compared with saline-treated and pair-fed controls. Methods: Rats with obesity received daily s.c. ad...... combines two highly relevant features, namely weight loss and insulin sensitivity, and is thus an excellent candidate for chronic treatment of obesity and insulin resistance....... a sustained weight loss of up to 20% without any significant weight reduction in the pair-fed groups. Decreases in adipose tissues and lipid deposition in the liver were observed, while plasma adiponectin was increased and plasma leptin levels were decreased. Acute administration of KBP-042 led to impaired......Objective: In this study, KBP-042, a dual amylin- and calcitonin-receptor agonist, was investigated as a treatment of obesity and insulin resistance in five different doses (0.625 μg/kg-10 μg/kg) compared with saline-treated and pair-fed controls. Methods: Rats with obesity received daily s...

  11. Approaching over 10 000-fold sensitivity increase in chiral capillary electrophoresis: Cation-selective exhaustive injection and sweeping cyclodextrin-modified micellar electrokinetic chromatography.

    Science.gov (United States)

    Mikuma, Toshiyasu; Iwata, Yuko T; Miyaguchi, Hajime; Kuwayama, Kenji; Tsujikawa, Kenji; Kanamori, Tatsuyuki; Kanazawa, Hideko; Inoue, Hiroyuki

    2016-11-01

    A novel and simple method that combines an online concentration technique with an enantioseparation technique for capillary electrophoresis-namely, cation-selective exhaustive injection and sweeping cyclodextrin-modified micellar electrokinetic chromatography (CSEI-sweeping CD-modified MEKC)-realizes the effective enantioseparation of cationic analytes while keeping a significant increase of detection sensitivity. This technique consists of a slight modification of the basic CSEI-sweeping MEKC. The main idea is to simply add an anionic CD as a chiral selector into the micellar buffer including sodium dodecyl sulfate, but not to change any other buffers in order to preserve the online concentration mechanism. When applied to analysis of the street drug, methamphetamine, the method achieved not only a baseline enantioseparation but also limits of detection (LODs; S/N = 3) of 70-90 pg/mL (ppt) for each isomer. This translates to a more than 10 000-fold improvement compared to the LODs by the usual injection method. The present technique, which was made from a slight modification of CSEI-sweeping MEKC, would give an attractive approach that is applicable to almost any analytes for which CSEI-sweeping MEKC is applicable; all that is required is the selection of an appropriate anionic CD to be added to the micellar buffer.

  12. An A20/AN1-type zinc finger protein modulates gibberellins and abscisic acid contents and increases sensitivity to abiotic stress in rice (Oryza sativa).

    Science.gov (United States)

    Zhang, Ye; Lan, Hongxia; Shao, Qiaolin; Wang, Ruqin; Chen, Hui; Tang, Haijuan; Zhang, Hongsheng; Huang, Ji

    2016-01-01

    The plant hormones gibberellins (GA) and abscisic acid (ABA) play important roles in plant development and stress responses. Here we report a novel A20/AN1-type zinc finger protein ZFP185 involved in GA and ABA signaling in the regulation of growth and stress response. ZFP185 was constitutively expressed in various rice tissues. Overexpression of ZFP185 in rice results in a semi-dwarfism phenotype, reduced cell size, and the decrease of endogenous GA3 content. By contrast, higher GA3 content was observed in RNAi plants. The application of exogenous GA3 can fully rescue the semi-dwarfism phenotype of ZFP185 overexpressing plants, suggesting the negative role of ZFP185 in GA biosynthesis. Besides GA, overexpression of ZFP185 decreased ABA content and expression of several ABA biosynthesis-related genes. Moreover, it was found that ZFP185, unlike previously known A20/AN1-type zinc finger genes, increases sensitivity to drought, cold, and salt stresses, implying the negative role of ZFP185 in stress tolerance. ZFP185 was localized in the cytoplasm and lacked transcriptional activation potential. Our study suggests that ZFP185 regulates plant growth and stress responses by affecting GA and ABA biosynthesis in rice.

  13. Increased sensitivity of 3D-Well enzyme-linked immunosorbent assay (ELISA) for infectious disease detection using 3D-printing fabrication technology.

    Science.gov (United States)

    Singh, Harpal; Shimojima, Masayuki; Fukushi, Shuetsu; Le Van, An; Sugamata, Masami; Yang, Ming

    2015-01-01

    Enzyme-linked Immunosorbent Assay or ELISA -based diagnostics are considered the gold standard in the demonstration of various immunological reaction including in the measurement of antibody response to infectious diseases and to support pathogen identification with application potential in infectious disease outbreaks and individual patients' treatment and clinical care. The rapid prototyping of ELISA-based diagnostics using available 3D printing technologies provides an opportunity for a further exploration of this platform into immunodetection systems. In this study, a '3D-Well' was designed and fabricated using available 3D printing platforms to have an increased surface area of more than 4 times for protein-surface adsorption compared to those of 96-well plates. The ease and rapidity in designing-product development-feedback cycle offered through 3D printing platforms provided an opportunity for its rapid assessment, in which a chemical etching process was used to make the surface hydrophilic followed by validation through the diagnostic performance of ELISA for infectious disease without modifying current laboratory practices for ELISA. The higher sensitivity of the 3D-Well (3-folds higher) compared to the 96-well ELISA provides a potential for the expansion of this technology towards miniaturization platforms to reduce time, volume of reagents and samples needed for laboratory or field diagnosis of infectious diseases including applications in other disciplines.

  14. Greater sensitivity to novelty in rats is associated with increased motor impulsivity following repeated exposure to a stimulating environment: implications for the etiology of impulse control deficits.

    Science.gov (United States)

    Ferland, Jacqueline-Marie N; Zeeb, Fiona D; Yu, Katrina; Kaur, Sukhbir; Taves, Matthew D; Winstanley, Catharine A

    2014-12-01

    Heightened motor impulsivity and increased novelty-seeking commonly co-occur in psychiatric disorders, including drug addiction. However, the relationship between these two phenomena remains unclear. One-time tests of novelty sensitivity commonly used in preclinical experiments, such as the open-field or novel-object test, fail to capture the fact that novelty-seekers repeatedly experience novel, stimulating situations. The present study therefore investigated whether repeated exposure to a novel, stimulating environment (SE) altered impulsive action. Male Long-Evans rats were trained to perform the five-choice serial reaction time task (5CSRTT) which measures motor impulsivity in the form of premature responding as well as attention and motivation. Animals were then exposed to a novel SE (1 h/day for 16 days) immediately prior to the 5CSRTT. Significant increases in premature responding were observed in a subgroup of reactive animals termed high responders (HR-SE). These rats were not more impulsive at baseline, and levels of impulsivity normalised once exposure to the SE was discontinued. No other aspect of 5CSRTT performance was affected by the SE challenge. We also determined that HR-SE rats were hyperactive in a novel environment. Biochemical analyses revealed changes in gene and protein expression within the dorsal hippocampus of HR-SE rats, including decreases in mRNA encoding the dopamine D1 receptor and brain-derived neurotrophic factor. These results indicate a novel mechanism by which impulsivity and novelty-reactivity interact that may enhance addiction vulnerability synergistically. Furthermore, studying such context-induced impulsivity may provide insight into the process by which environmental load precipitates psychiatric symptoms in impulse control disorders.

  15. Nucleotide excision repair deficiency increases levels of acrolein-derived cyclic DNA adduct and sensitizes cells to apoptosis induced by docosahexaenoic acid and acrolein.

    Science.gov (United States)

    Pan, Jishen; Sinclair, Elizabeth; Xuan, Zhuoli; Dyba, Marcin; Fu, Ying; Sen, Supti; Berry, Deborah; Creswell, Karen; Hu, Jiaxi; Roy, Rabindra; Chung, Fung-Lung

    2016-07-01

    The acrolein derived cyclic 1,N(2)-propanodeoxyguanosine adduct (Acr-dG), formed primarily from ω-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) under oxidative conditions, while proven to be mutagenic, is potentially involved in DHA-induced apoptosis. The latter may contribute to the chemopreventive effects of DHA. Previous studies have shown that the levels of Acr-dG are correlated with apoptosis induction in HT29 cells treated with DHA. Because Acr-dG is shown to be repaired by the nucleotide excision repair (NER) pathway, to further investigate the role of Acr-dG in apoptosis, in this study, NER-deficient XPA and its isogenic NER-proficient XAN1 cells were treated with DHA. The Acr-dG levels and apoptosis were sharply increased in XPA cells, but not in XAN1 cells when treated with 125μM of DHA. Because DHA can induce formation of various DNA damage, to specifically investigate the role of Acr-dG in apoptosis induction, we treated XPA knockdown HCT116+ch3 cells with acrolein. The levels of both Acr-dG and apoptosis induction increased significantly in the XPA knockdown cells. These results clearly demonstrate that NER deficiency induces higher levels of Acr-dG in cells treated with DHA or acrolein and sensitizes cells to undergo apoptosis in a correlative manner. Collectively, these results support that Acr-dG, a ubiquitously formed mutagenic oxidative DNA adduct, plays a role in DHA-induced apoptosis and suggest that it could serve as a biomarker for the cancer preventive effects of DHA.

  16. THE PRESENCE OF A B SUBUNIT INCREASES SENSITIVITY OF SODIUM CHANNEL NAV1.3, BUT NOT NAV1.2, TO TYPE II PYRETHROIDS.

    Science.gov (United States)

    Voltage-sensitive sodium channels (VSSCs) are a primary target of pyrethroid insecticides. VSSCs are comprised of a pore-forming ¿ and auxillary ß subunits, and multiple isoforms of both subunit types exist. The sensitivity of different isoform combinations to pyrethroids has not...

  17. Increased pain sensitivity but normal function of exercise induced analgesia in hip and knee osteoarthritis - treatment effects of neuromuscular exercise and total joint replacement

    DEFF Research Database (Denmark)

    Kosek, E; Roos, Ewa M.; Ageberg, E;

    2013-01-01

    To assess exercise induced analgesia (EIA) and pain sensitivity in hip and knee osteoarthritis (OA) and to study the effects of neuromuscular exercise and surgery on these parameters.......To assess exercise induced analgesia (EIA) and pain sensitivity in hip and knee osteoarthritis (OA) and to study the effects of neuromuscular exercise and surgery on these parameters....

  18. Installation of the light tight cover for the SSD modules (the modules are behind the aluminium plate). The silicon sensors are sensitive to light tight, so ambient light will increase the noise and may even damage them.

    CERN Multimedia

    Nooren, G.

    2004-01-01

    Installation of the light tight cover for the SSD modules (the modules are behind the aluminium plate). The silicon sensors are sensitive to light tight , so ambient light will increase the noise and may even damage them.

  19. Ablation of the transcriptional regulator Id1 enhances energy expenditure, increases insulin sensitivity, and protects against age and diet induced insulin resistance, and hepatosteatosis.

    Science.gov (United States)

    Satyanarayana, Ande; Klarmann, Kimberly D; Gavrilova, Oksana; Keller, Jonathan R

    2012-01-01

    Obesity is a major health concern that contributes to the development of diabetes, hyperlipidemia, coronary artery disease, and cancer. Id proteins are helix-loop-helix transcription factors that regulate the proliferation and differentiation of cells from multiple tissues, including adipocytes. We screened mouse tissues for the expression of Id1 and found that Id1 protein is highly expressed in brown adipose tissue (BAT) and white adipose tissue (WAT), suggesting a role for Id1 in adipogenesis and cell metabolism. Id1(-/-) mice are viable but show a significant reduction in fat mass (P<0.005) over the life of the animal that was not due to decreased number of adipocytes. Analysis of Id1(-/-) mice revealed higher energy expenditure, increased lipolysis, and fatty acid oxidation, resulting in reduced triglyceride accumulation in WAT compared to Id1(+/+) mice. Serum levels of triglycerides (193.9±32.2 vs. 86.5±33.8, P<0.0005), cholesterol (189.4±33.8 vs. 110.6±8.23, P<0.0005) and leptin (1263±835 vs. 222±260, P<0.005) were significantly lower in aged Id1(-/-) mice compared to Id1(+/+) mice. Id1-deficient mice have higher resting (P<0.005) and total (P<0.05) O(2) consumption and lower respiratory exchange ratio (P<0.005), confirming that Id1(-/-) mice use a higher proportion of lipid as an energy source for the increased energy expenditure. The expression of PGC1α and UCP1 were 2- to 3-fold up-regulated in Id1(-/-) BAT, suggesting that loss of Id1 increases thermogenesis. As a consequence of higher energy expenditure and reduced fat mass, Id1(-/-) mice displayed enhanced insulin sensitivity. Id1 deficiency protected mice against age- and high-fat-diet-induced adiposity, insulin resistance, and hepatosteatosis. Our findings suggest that Id1 plays a critical role in the regulation of energy homeostasis and could be a potential target in the treatment of insulin resistance and fatty liver disease.

  20. Inhibition of mitogen activated protein kinases increases the sensitivity of A549 lung cancer cells to the cytotoxicity induced by a kava chalcone analog.

    Science.gov (United States)

    Warmka, Janel K; Solberg, Eric L; Zeliadt, Nicholette A; Srinivasan, Balasubramanian; Charlson, Aaron T; Xing, Chengguo; Wattenberg, Elizabeth V

    2012-08-03

    We are interested in investigating the biological activity of chalcones, a major class of compounds found in the beverage kava, in order to develop potent and selective chemopreventive candidates. Consumption of kava in the South Pacific Islands is inversely correlated with cancer incidence, even among smokers. Accordingly, chalcones have anti-cancer activities in animal and cell culture models. To investigate signaling pathways that affect chalcone action we studied a potent analog, (E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (chalcone-24). Chalcone-24 was selected from a series of chalcone analogs that were synthesized based on the structures derived from flavokawain compounds found in kava, and screened in A549 lung cancer cells for induction of cytotoxicity and inhibition of NF-κB, a transcription factor associated with cell survival. Incubation of A549 cells with chalcone-24 resulted in a dose-dependent inhibition of cell viability, inhibition of NF-κB, activation of caspases, and activation of extracellular signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK); ERK1/2 and JNK are mitogen activated protein kinases that play central roles in regulating cell fate. Pharmacological inhibitors of ERK1/2 or JNK increased the sensitivity of A549 cells to chalcone-24-induced cytotoxicity, without affecting NF-κB or caspase activity. These results will help refine the synthesis of chalcone analogs to maximize the combination of actions required to prevent and treat cancer.

  1. Angiotensin-converting enzyme inhibition and food restriction in diabetic mice do not correct the increased sensitivity for ischemia-reperfusion injury

    Directory of Open Access Journals (Sweden)

    Van der Mieren Gerry

    2012-08-01

    Full Text Available Abstract Background The number of patients with diabetes or the metabolic syndrome reaches epidemic proportions. On top of their diabetic cardiomyopathy, these patients experience frequent and severe cardiac ischemia-reperfusion (IR insults, which further aggravate their degree of heart failure. Food restriction and angiotensin-converting enzyme inhibition (ACE-I are standard therapies in these patients but the effects on cardiac IR injury have never been investigated. In this study, we tested the hypothesis that 1° food restriction and 2° ACE-I reduce infarct size and preserve cardiac contractility after IR injury in mouse models of diabetes and the metabolic syndrome. Methods C57Bl6/J wild type (WT mice, leptin deficient ob/ob (model for type II diabetes and double knock-out (LDLR-/-;ob/ob, further called DKO mice with combined leptin and LDL-receptor deficiency (model for metabolic syndrome were used. The effects of 12 weeks food restriction or ACE-I on infarct size and load-independent left ventricular contractility after 30 min regional cardiac ischemia were investigated. Differences between groups were analyzed for statistical significance by Student’s t-test or factorial ANOVA followed by a Fisher’s LSD post hoc test. Results Infarct size was larger in ob/ob and DKO versus WT. Twelve weeks of ACE-I improved pre-ischemic left ventricular contractility in ob/ob and DKO. Twelve weeks of food restriction, with a weight reduction of 35-40%, or ACE-I did not reduce the effect of IR. Conclusion ACE-I and food restriction do not correct the increased sensitivity for cardiac IR-injury in mouse models of type II diabetes and the metabolic syndrome.

  2. Galactosylated fucose epitopes in nematodes: increased expression in a Caenorhabditis mutant associated with altered lectin sensitivity and occurrence in parasitic species.

    Science.gov (United States)

    Yan, Shi; Bleuler-Martinez, Silvia; Plaza, David Fernando; Künzler, Markus; Aebi, Markus; Joachim, Anja; Razzazi-Fazeli, Ebrahim; Jantsch, Verena; Geyer, Rudolf; Wilson, Iain B H; Paschinger, Katharina

    2012-08-17

    The modification of α1,6-linked fucose residues attached to the proximal (reducing-terminal) core N-acetylglucosamine residue of N-glycans by β1,4-linked galactose ("GalFuc" epitope) is a feature of a number of invertebrate species including the model nematode Caenorhabditis elegans. A pre-requisite for both core α1,6-fucosylation and β1,4-galactosylation is the presence of a nonreducing terminal N-acetylglucosamine; however, this residue is normally absent from the final glycan structure in invertebrates due to the action of specific hexosaminidases. Previously, we have identified two hexosaminidases (HEX-2 and HEX-3) in C. elegans, which process N-glycans. In the present study, we have prepared a hex-2;hex-3 double mutant, which possesses a radically altered N-glycomic profile. Whereas in the double mutant core α1,3-fucosylation of the proximal N-acetylglucosamine was abolished, the degree of galactosylation of core α1,6-fucose increased, and a novel Galα1,2Fucα1,3 moiety attached to the distal core N-acetylglucosamine residue was detected. Both galactosylated fucose moieties were also found in two parasitic nematodes, Ascaris suum and Oesophagostomum dentatum. As core modifications of N-glycans are known targets for fungal nematotoxic lectins, the sensitivity of the C. elegans double hexosaminidase mutant was assessed. Although this mutant displayed hypersensitivity to the GalFuc-binding lectin CGL2 and the N-acetylglucosamine-binding lectin XCL, the mutant was resistant to CCL2, which binds core α1,3-fucose. Thus, the use of C. elegans mutants aids the identification of novel N-glycan modifications and the definition of in vivo specificities of nematotoxic lectins with potential as anthelmintic agents.

  3. Depletion of OLFM4 gene inhibits cell growth and increases sensitization to hydrogen peroxide and tumor necrosis factor-alpha induced-apoptosis in gastric cancer cells

    Directory of Open Access Journals (Sweden)

    Liu Rui-hua

    2012-04-01

    Full Text Available Abstract Background Human olfactomedin 4 (OLFM4 gene is a secreted glycoprotein more commonly known as the anti-apoptotic molecule GW112. OLFM4 is found to be frequently up-regulated in many types of human tumors including gastric cancer and it was believed to play significant role in the progression of gastric cancer. Although the function of OLFM4 has been indicated in many studies, recent evidence strongly suggests a cell or tissue type-dependent role of OLFM4 in cell growth and apoptosis. The aim of this study is to examine the role of gastric cancer-specific expression of OLFM4 in cell growth and apoptosis resistance. Methods OLFM4 expression was eliminated by RNA interference in SGC-7901 and MKN45 cells. Cell proliferation, anchorage-independent growth, cell cycle and apoptosis were characterized in vitro. Tumorigenicity was analyzed in vivo. The apoptosis and caspase-3 activation in response to hydrogen peroxide (H2O2 or tumor necrosis factor-alpha (TNF α were assessed in the presence or absence of caspase inhibitor Z-VAD-fmk. Results The elimination of OLFM4 protein by RNA interference in SGC-7901 and MKN45 cells significantly inhibits tumorigenicity both in vitro and in vivo by induction of cell G1 arrest (all P 2O2 or TNF α-induced apoptosis and caspase-3 activity (all P 2O2 or TNF α-induced apoptosis in OLFM4 knockdown cells (all P Conclusion Our study suggests that depletion of OLFM4 significantly inhibits tumorigenicity of the gastric cancer SGC-7901 and MKN45 cells. Blocking OLFM4 expression can sensitize gastric cancer cells to H2O2 or TNF α treatment by increasing caspase-3 dependent apoptosis. A combination strategy based on OLFM4 inhibition and anticancer drugs treatment may provide therapeutic potential in gastric cancer intervention.

  4. Combination of high-sensitivity C-reactive protein and homocysteine may predict an increased risk of coronary artery disease in Korean population

    Institute of Scientific and Technical Information of China (English)

    CHO Doo-Yeoun; KIM Kyu-Nam; KIM Kwang-Min; LEE Duck-Joo; KIM Bom-Taeck

    2012-01-01

    Background The association of emerging biomarkers such as high-sensitivity C-reactive protein (hs-CRP),homocysteine and fibrinogen with the risk of coronary artery disease (CAD) is still uncertain in Asian population including Koreans and little is known about the combined effect of biomarkers on the risk of CAD.Methods A total of 10 650 subjects (6538 men and 4112 women) were enrolled in this study.A 10-year CAD risk was calculated using Framingham risk score modified by the National Cholesterol Education Program (NCEP) Adult Treatment Panel Ⅲ (ATP Ⅲ ) and levels of circulating hs-CRP,homocysteine and fibrinogen were measured using validated assays.Results The 10-year CAD risk gradually augmented with increase in the circulating levels of hs-CRP,homocysteine and fibrinogen.For the highest quartile of hs-CRP,odds ratio (OR) of high-risk for CAD (10-year risk ≥20%) compared with the lowest quartile was 3.97 (95% C/:2.51-6.29).For homocysteine and fibrinogen,ORs in the highest quartile compared to the lowest quartile were 5.10 (95% Cl:3.05-8.53,P <0.001) and 1.46 (95% Cl:0.69-3.11,P=0.325),respectively.OR of high-risk for CAD in both the highest quartile of hs-CRP and homocysteine was 9.05 (95% CI:5.30-15.45) compared with the below median of hs-CRP and homocysteine.Conclusions The present study demonstrated that hs-CRP and homocysteine are well associated with the 10-year CAD risk estimated using NCEP ATP Ⅲ in Koreans and combination of hs-CRP and homocysteine can have strong synergyin predicting the development of CAD.

  5. Suppression of microRNA-31 increases sensitivity to 5-FU at an early stage, and affects cell migration and invasion in HCT-116 colon cancer cells

    Directory of Open Access Journals (Sweden)

    Sun Xiao-Feng

    2010-11-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are endogenously expressed noncoding RNAs with important biological and pathological functions. Although several studies have shown that microRNA-31 (miR-31 is obviously up-regulated in colorectal cancer (CRC, there is no study on the functional roles of miR-31 in CRC. Methods Anti-miR™ miRNA 31 inhibitor (anti-miR-31 is a sequence-specific and chemically modified oligonucleotide to specifically target and knockdown miR-31 molecule. The effect of anti-miR-31 transfection was investigated by real-time PCR. HCT-116p53+/+ and HCT-116p53-/-colon cancer cells were treated by anti-miR-31 with or without 5-fluorouracil (5-FU, cell proliferation was determined by MTT assay; apoptosis was detected by DAPI staining; cell cycle was evaluated by flow cytometry; colony formation, migration and invasion assays were performed to investigate the effect of suppression of miR-31 on the cell lines. Results Real-time PCR results showed that anti-miR-31 was efficiently introduced into the cells and reduced miR-31 levels to 44.1% in HCT-116p53+/+ and 67.8% in HCT-116p53-/-cell line (p = 0.042 and 0.046. MTT results showed that anti-miR-31 alone had no effect on the proliferation of HCT-116p53+/+ or HCT-116p53-/-. However, when combined with 5-FU, anti-miR-31 inhibited the proliferation of the two cell lines as early as 24 h after exposure to 5-FU (p = 0.038 and 0.044. Suppression of miR-31 caused a reduction of the migratory cells by nearly 50% compared with the negative control in both HCT-116p53+/+ and HCT-116p53-/-(p = 0.040 and 0.001. The invasive ability of the cells were increased by 8-fold in HCT-116p53+/+ and 2-fold in HCT-116p53-/- (p = 0.045 and 0.009. Suppression of miR-31 had no effect on cell cycle and colony formation (p > 0.05. Conclusions Suppression of miR-31 increases sensitivity to 5-FU at an early stage, and affects cell migration and invasion in HCT-116 colon cancer cells.

  6. Increased abundance of insulin/insulin-like growth factor-I hybrid receptors in skeletal muscle of obese subjects is correlated with in vivo insulin sensitivity.

    Science.gov (United States)

    Federici, M; Porzio, O; Lauro, D; Borboni, P; Giovannone, B; Zucaro, L; Hribal, M L; Sesti, G

    1998-08-01

    We reported that in noninsulin-dependent diabetes melitus (NIDDM) patients expression of insulin/insulin-like growth factor I (IGF-I) hybrid receptors is increased in insulin target tissues. Whether this is a defect associated with NIDDM or represents a generalized abnormality associated with insulin resistant states is still unsettled. To address this, we applied a microwell-based immunoassay to measure abundance of insulin receptors, type 1 IGF receptors, and hybrid receptors in muscle of eight normal and eight obese subjects. Maximal insulin binding to insulin receptors was lower in obese than in control subjects (B/T = 1.8 +/- 0.20 and 2.6 +/- 0.30; P < 0.03, respectively) and was negatively correlated with insulinemia (r = -0.60; P < 0.01). Maximal IGF-I binding to type 1 IGF receptors was higher in obese than in controls (B/T = 1.9 +/- 0.20 and 0.86 +/- 0.10; P < 0.0001, respectively) and was negatively correlated with plasma IGF-I levels (r = -0.69; P < 0.003). Hybrid receptor abundance was higher in obese than in normal subjects (B/T = 1.21 +/- 0.14 and 0.44 +/- 0.06; P < 0.0003, respectively) and was negatively correlated with insulin binding (r = -0.60; P < 0.01) and positively correlated with IGF-I binding (r = 0.92; P < 0.0001). Increased abundance of hybrids was correlated with insulinemia (r = 0.70; P < 0.002) and body mass index (r = 0.71; P < 0.0019), whereas it was negatively correlated with in vivo insulin sensitivity measured by ITT (r = -0.67; P < 0.016). These results indicate that downregulation of insulin receptors or upregulation of type 1 IGF receptors because of changes in plasma insulin and IGF-I levels may result in modifications in hybrid receptor abundance.

  7. Adding Papillomacular Bundle Measurements to Standard Optical Coherence Tomography Does Not Increase Sensitivity to Detect Prior Optic Neuritis in Patients with Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Mona Laible

    Full Text Available To improve the detection of retinal nerve fiber layer (RNFL thinning in multiple sclerosis (MS, a special peripapillary ring scanning algorithm (N-site RNFL, N-RNFL was developed for spectral domain optical coherence tomography (SD-OCT. In contrast to the standard protocol (ST-RNFL scanning starts nasally, not temporally, and provides an additional sector of analysis, the papillomacular bundle (PMB. We aimed to ascertain whether the temporal RNFL differs between the two techniques, whether N-RNFL is more sensitive than ST-RNFL to detect previous optic neuritis (ON, and whether analyzing the PMB adds additional sensitivity. Furthermore, we investigated whether RNFL is associated with disease severity and/or disease duration.We conducted a cross-sectional case-control study of 38 patients with MS, of whom 24 had a history of ON, and 40 healthy controls (HC. Subjects with ON within the previous 6 months were excluded. Records included clinical characteristics, visual evoked potentials (VEP, and SD-OCT in both techniques.In a total of 73 evaluable MS eyes, temporal N-RNFL was abnormal in 17.8%, temporal ST-RNFL in 19.2%, and the PMB-RNFL in 21.9%. In ON eyes, the sensitivity of temporal N-RNFL and ST-RNFL did not differ significantly (37.0%/33.3%, p = 0.556. The sensitivity of VEP was 85.2%. RNFL thickness was associated with disease severity in all eyes, with and without a history of ON, and with disease duration.The two OCT techniques detected previous ON with similar sensitivity, but the sensitivity of VEPs was superior to that of both N-RNFL and ST-RNFL. Our results indicate that the widely used ST-RNFL technique is appropriate for peripapillary RNFL measurements in MS patients.

  8. Increased myofilament Ca2+ sensitivity and diastolic dysfunction as early consequences of Mybpc3 mutation in heterozygous knock-in mice.

    Science.gov (United States)

    Fraysse, Bodvaël; Weinberger, Florian; Bardswell, Sonya C; Cuello, Friederike; Vignier, Nicolas; Geertz, Birgit; Starbatty, Jutta; Krämer, Elisabeth; Coirault, Catherine; Eschenhagen, Thomas; Kentish, Jonathan C; Avkiran, Metin; Carrier, Lucie

    2012-06-01

    Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in MYBPC3 encoding cardiac myosin-binding protein C (cMyBP-C). The mechanisms leading from gene mutations to the HCM phenotype remain incompletely understood, partially because current mouse models of HCM do not faithfully reflect the human situation and early hypertrophy confounds the interpretation of functional alterations. The goal of this study was to evaluate whether myofilament Ca(2+) sensitization and diastolic dysfunction are associated or precede the development of left ventricular hypertrophy (LVH) in HCM. We evaluated the function of skinned and intact cardiac myocytes, as well as the intact heart in a recently developed Mybpc3-targeted knock-in mouse model carrying a point mutation frequently associated with HCM. Compared to wild-type, 10-week old homozygous knock-in mice exhibited i) higher myofilament Ca(2+) sensitivity in skinned ventricular trabeculae, ii) lower diastolic sarcomere length, and faster Ca(2+) transient decay in intact myocytes, and iii) LVH, reduced fractional shortening, lower E/A and E'/A', and higher E/E' ratios by echocardiography and Doppler analysis, suggesting systolic and diastolic dysfunction. In contrast, heterozygous knock-in mice, which mimic the human HCM situation, did not exhibit LVH or systolic dysfunction, but exhibited higher myofilament Ca(2+) sensitivity, faster Ca(2+) transient decay, and diastolic dysfunction. These data demonstrate that myofilament Ca(2+) sensitization and diastolic dysfunction are early phenotypic consequences of Mybpc3 mutations independent of LVH. The accelerated Ca(2+) transients point to compensatory mechanisms directed towards normalization of relaxation. We propose that HCM is a model for diastolic heart failure and this mouse model could be valuable in studying mechanisms and treatment modalities.

  9. Zoledronic acid increases docetaxel cytotoxicity through pMEK and Mcl-1 inhibition in a hormone-sensitive prostate carcinoma cell line

    OpenAIRE

    Silvestrini Rosella; Tesei Anna; Vannini Ivan; Ulivi Paola; Carloni Silvia; Brigliadori Giovanni; Fabbri Francesco; Amadori Dino; Zoli Wainer

    2008-01-01

    Abstract Background In prostate cancer, the identification of drug combinations that could reduce the tumor cell population and rapidly eradicate hormone-resistant cells potentially present would be a remarkable breakthrough in the treatment of this disease. Methods The study was performed on a hormone-sensitive prostate cancer cell line (LNCaP) grown in normal or hormone-deprived charcoal-stripped (c.s.) medium. Cell viability and apoptosis were assessed by SRB assay and Annexin-V/TUNEL assa...

  10. CB1 Cannabinoid Agonist (WIN55,212-2) Within the Basolateral Amygdala Induced Sensitization to Morphine and Increased the Level of μ-Opioid Receptor and c-fos in the Nucleus Accumbens.

    Science.gov (United States)

    Molaei, Marzieh; Fatahi, Zahra; Zaringhalam, Jalal; Haghparast, Abbas

    2016-04-01

    The basolateral amygdala (BLA) is rich of CB1 cannabinoid receptors (CB1R) and has reciprocal connections with the nucleus accumbens (NAc) which is involved in opioid sensitization. In this study, effects of intra-BLA administration of CB1R agonist on sensitization to antinociceptive effect of morphine and changes in the levels of μ-opioid receptor (MOR), p-CREB, and c-fos in the NAc were investigated. Animals received intra-BLA microinjection of CB1R agonist (WIN55,212-2) once daily for 3 days consecutively (sensitization period). After 5 days free of drug, tail-flick test was performed before and after the administration of an ineffective dose of morphine. Afterward, the levels of MOR, p-CREB, and c-fos proteins were measured in the NAc by Western blot analysis. The results indicated that intra-BLA injection of WIN55,212-2 during sensitization period resulted in the induction of antinociceptive responses by ineffective dose of morphine and caused a significant increase in the MOR and c-fos levels but not p-CREB/CREB ratio in the NAc. These finding revealed that CB1 receptor agonist in the BLA induces development of morphine sensitization and increases expression of MOR in the NAc. It seems that c-fos is one of the important factors involved in the induction of sensitization to antinociceptive effect of morphine.

  11. Utilizing 1-Meter Land Cover Data to Increase Sensitivity of Studies Exploring Relationships between Urban Natural Spaces and Health across Multiple Communities

    Science.gov (United States)

    Purpose: Previous studies have positively correlated human nature exposures with health promoting outcomes such as increased physical activity, improved cognitive function, increased social engagement, and reduced ambient air pollution. When using remotely-sensed data to investig...

  12. Increased sensitivity of the circadian system to temporal changes in the feeding regime of spontaneously hypertensive rats - a potential role for Bmal2 in the liver.

    Directory of Open Access Journals (Sweden)

    Lenka Polidarová

    Full Text Available The mammalian timekeeping system generates circadian oscillations that rhythmically drive various functions in the body, including metabolic processes. In the liver, circadian clocks may respond both to actual feeding conditions and to the metabolic state. The temporal restriction of food availability to improper times of day (restricted feeding, RF leads to the development of food anticipatory activity (FAA and resets the hepatic clock accordingly. The aim of this study was to assess this response in a rat strain exhibiting complex pathophysiological symptoms involving spontaneous hypertension, an abnormal metabolic state and changes in the circadian system, i.e., in spontaneously hypertensive rats (SHR. The results revealed that SHR were more sensitive to RF compared with control rats, developing earlier and more pronounced FAA. Whereas in control rats, the RF only redistributed the activity profiles into two bouts (one corresponding to FAA and the other corresponding to the dark phase, in SHR the RF completely phase-advanced the locomotor activity according to the time of food presentation. The higher behavioral sensitivity to RF was correlated with larger phase advances of the hepatic clock in response to RF in SHR. Moreover, in contrast to the controls, RF did not suppress the amplitude of the hepatic clock oscillation in SHR. In the colon, no significant differences in response to RF between the two rat strains were detected. The results suggested the possible involvement of the Bmal2 gene in the higher sensitivity of the hepatic clock to RF in SHR because, in contrast to the Wistar rats, the rhythm of Bmal2 expression was advanced similarly to that of Bmal1 under RF. Altogether, the data demonstrate a higher behavioral and circadian responsiveness to RF in the rat strain with a cardiovascular and metabolic pathology and suggest a likely functional role for the Bmal2 gene within the circadian clock.

  13. miRNA-181b increases the sensitivity of pancreatic ductal adenocarcinoma cells to gemcitabine in vitro and in nude mice by targeting BCL-2.

    Science.gov (United States)

    Cai, Baobao; An, Yong; Lv, Nan; Chen, Jianmin; Tu, Min; Sun, Jie; Wu, Pengfei; Wei, Jishu; Jiang, Kuirong; Miao, Yi

    2013-05-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease and is usually resistant to chemotherapy. MicroRNA‑181b (miR-181b) has been reported to be associated with chemoresistance in various types of cancer. In this study, we investigated the effects of miR-181b on the chemosensitivity of PDAC cells to gemcitabine and the underlying molecular events. miR-181b mimics and inhibitors were synthesized for transient gene transfection in vitro. Lentivirus carrying miR-181b mimics were used to infect PDAC cells for nude mouse xenograft assays by implanting infected PDAC cells into recipient mice. Cell viability was determined by MTT assays, while gene expression was assessed using qRT-PCR, western blot analysis and enzyme-linked immunosorbent assay (ELISA). miR-181b targeting BCL-2 expression was assessed by a dual-luciferase activity assay. The data showed that miRNA-181b expression sensitized PDAC cells to gemcitabine treatment. Although gemcitabine-resistant PDAC cell sublines (SW1990/GR and CFPAC-1/GR) expressed higher levels of miRNA-181b, gemcitabine induced higher levels of apoptosis in PDAC cells transfected with miRNA-181b mimics. The nude mouse xenograft assay data showed that miR-181b transfection also sensitized the cells to gemcitabine treatment in vivo. Molecularly, bioinformatics data predicted that miR-181b was able to bind to BCL-2 mRNA 3'UTR. The dual luciferase activity assay revealed that miRNA-181b downregulated BCL-2 expression. The results from western blot analysis showed a reduced BCL-2 expression following miR-181b transfection but an enhanced caspase-3 activity in miRNA-181b mimic-transfected PDAC cells. This study demonstrates that miRNA-181b sensitizes PDAC cells to gemcitabine by targeting BCL-2.

  14. Inhibition of P-Selectin and PSGL-1 Using Humanized Monoclonal Antibodies Increases the Sensitivity of Multiple Myeloma Cells to Bortezomib.

    Science.gov (United States)

    Muz, Barbara; Azab, Feda; de la Puente, Pilar; Rollins, Scott; Alvarez, Richard; Kawar, Ziad; Azab, Abdel Kareem

    2015-01-01

    Multiple myeloma (MM) is a plasma cell malignancy localized in the bone marrow. Despite the introduction of novel therapies majority of MM patients relapse. We have previously shown that inhibition of P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) play a key role in proliferation of MM and using small-molecule inhibitors of P-selectin/PSGL-1 sensitized MM cells to therapy. However, these small-molecule inhibitors had low specificity to P-selectin and showed poor pharmacokinetics. Therefore, we tested blocking of P-selectin and PSGL-1 using functional monoclonal antibodies in order to sensitize MM cells to therapy. We have demonstrated that inhibiting the interaction between MM cells and endothelial and stromal cells decreased proliferation in MM cells and in parallel induced loose-adhesion to the primary tumor site to facilitate egress. At the same time, blocking this interaction in vivo led to MM cells retention in the circulation and delayed homing to the bone marrow, thus exposing MM cells to bortezomib which contributed to reduced tumor growth and better mice survival. This study provides a better understanding of the biology of P-selectin and PSGL-1 and their roles in dissemination and resensitization of MM to treatment.

  15. Inhibition of P-Selectin and PSGL-1 Using Humanized Monoclonal Antibodies Increases the Sensitivity of Multiple Myeloma Cells to Bortezomib

    Directory of Open Access Journals (Sweden)

    Barbara Muz

    2015-01-01

    Full Text Available Multiple myeloma (MM is a plasma cell malignancy localized in the bone marrow. Despite the introduction of novel therapies majority of MM patients relapse. We have previously shown that inhibition of P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1 play a key role in proliferation of MM and using small-molecule inhibitors of P-selectin/PSGL-1 sensitized MM cells to therapy. However, these small-molecule inhibitors had low specificity to P-selectin and showed poor pharmacokinetics. Therefore, we tested blocking of P-selectin and PSGL-1 using functional monoclonal antibodies in order to sensitize MM cells to therapy. We have demonstrated that inhibiting the interaction between MM cells and endothelial and stromal cells decreased proliferation in MM cells and in parallel induced loose-adhesion to the primary tumor site to facilitate egress. At the same time, blocking this interaction in vivo led to MM cells retention in the circulation and delayed homing to the bone marrow, thus exposing MM cells to bortezomib which contributed to reduced tumor growth and better mice survival. This study provides a better understanding of the biology of P-selectin and PSGL-1 and their roles in dissemination and resensitization of MM to treatment.

  16. Enhancement of malate-production and increase in sensitivity to dimethyl succinate by mutation of the VID24 gene in Saccharomyces cerevisiae.

    Science.gov (United States)

    Negoro, Hiroaki; Kotaka, Atsushi; Matsumura, Kengo; Tsutsumi, Hiroko; Hata, Yoji

    2016-06-01

    Malate in sake (a Japanese alcoholic beverage) is an important component for taste that is produced by yeasts during alcoholic fermentation. To date, many researchers have developed methods for breeding high-malate-producing yeasts; however, genes responsible for the high-acidity phenotype are not known. We determined the mutated gene involved in high malate production in yeast, isolated as a sensitive mutant to dimethyl succinate. In the comparative whole genome analysis between high-malate-producing strain and its parent strain, one of the non-synonymous substitutions was identified in the VID24 gene. The mutation of VID24 resulted in enhancement of malate-productivity and sensitivity to dimethyl succinate. The mutation appeared to lead to a deficiency in Vid24p function. Furthermore, disruption of cytoplasmic malate dehydrogenase (Mdh2p) gene in the VID24 mutant inhibited the high-malate-producing phenotype. Vid24p is known as a component of the multisubunit ubiquitin ligase and participates in the degradation of gluconeogenic enzymes such as Mdh2p. We suggest that the enhancement of malate-productivity results from an accumulation of Mdh2p due to the loss of Vid24p function. These findings propose a novel mechanism for the regulation of organic acid production in yeast cells by the component of ubiquitin ligase, Vid24p.

  17. A simplification of the enzyme-linked immunospot technique. Increased sensitivity for cells secreting IgG antibodies to Haemophilus influenzae type b capsular polysaccharide

    DEFF Research Database (Denmark)

    Barington, T; Sparholt, S; Juul, L

    1992-01-01

    A simplified enzyme-linked immunospot (ELISPOT) technique is described for the detection of cells secreting antibodies to tetanus toxoid (TT), diphtheria toxoid (DT) or Haemophilus influenzae type b capsular polysaccharide (PRP). By combining the cell suspension with the enzyme-linked secondary...... antibodies in one incubation, the second incubation and washing procedure could be omitted from the original technique. The simplified assay had the same sensitivity for anti-TT and anti-DT spot-forming cells as the ordinary ELISPOT assay. The IgG anti-PRP spots were, however, improved both in quality...... and in quantity (median: 40% more spots), while the detection of IgM and IgA anti-PRP spot-forming cells was the same in the two techniques. This simplified technique can probably also be used to save time in other antigen systems and should be considered when designing ELISPOT assays for the detection...

  18. Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression

    Energy Technology Data Exchange (ETDEWEB)

    Li, Luchuan; Lv, Bin; Chen, Bo [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China); Guan, Ming [Department of General Surgery, Qihe People' s Hospital, Qihe, Shandong 251100 (China); Sun, Yongfeng [Department of General Surgery, Licheng District People' s Hospital, Jinan, Shandong 250115 (China); Li, Haipeng [Department of General Surgery, Caoxian People' s Hospital, Caoxian, Shandong 274400 (China); Zhang, Binbin; Ding, Changyuan; He, Shan [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China); Zeng, Qingdong, E-mail: qingdz0201@163.com [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China)

    2015-07-10

    Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, was picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na{sup +}/I{sup −} symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC). - Highlights: • Significant upregulated miR-146b was picked up from thyroid relative miRNAs in DTC. • MiR-146b was negatively regulated by HDAC3 in normal thyroid carcinoma cells. • NIS activity and expression could be regulated by miR-146b in thyroid carcinoma. • MiR-146b inhibition could recover the decreased radioiodine-sensitivity of DTC cells.

  19. Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In-Gyu, E-mail: igkim@kaeri.re.kr [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Lee, Jae-Ha [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Kim, Seo-Yoen; Kim, Jeong-Yul [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Cho, Eun-Wie [Epigenomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of)

    2014-11-21

    Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation.

  20. Prolonged Increase in the Sensitivity of the Posterior Ventral Tegmental Area to the Reinforcing Effects of Ethanol following Repeated Exposure to Cycles of Ethanol Access and Deprivation

    OpenAIRE

    Rodd, Zachary A.; Bell, Richard L.; McQueen, Victoria K.; Davids, Michelle R.; Hsu, Cathleen C.; Murphy, James M.; Li, Ting-Kai; Lumeng, Lawrence; McBride, William J.

    2005-01-01

    The posterior ventral tegmental area (VTA) is a neuroanatomical substrate mediating the reinforcing effects of ethanol in rats. Repeated alcohol deprivations produce robust ethanol intakes of alcohol-preferring (P) rats during relapse and increase the reinforcing effects of oral alcohol self-administration. The objective of this study was to test the hypothesis that alcohol drinking and repeated alcohol deprivations will increase the reinforcing effects of ethanol within the posterior VTA of ...

  1. Combined evaluation of a panel of protein and miRNA serum-exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity.

    Science.gov (United States)

    Madhavan, Bindhu; Yue, Shijing; Galli, Uwe; Rana, Sanyukta; Gross, Wolfgang; Müller, Miryam; Giese, Nathalia A; Kalthoff, Holger; Becker, Thomas; Büchler, Markus W; Zöller, Margot

    2015-06-01

    Late diagnosis contributes to pancreatic cancer (PaCa) dismal prognosis, urging for reliable, early detection. Serum-exosome protein and/or miRNA markers might be suitable candidates, which we controlled for patients with PaCa. Protein markers were selected according to expression in exosomes of PaCa cell line culture supernatants, but not healthy donors' serum-exosomes. miRNA was selected according to abundant recovery in microarrays of patients with PaCa, but not healthy donors' serum-exosomes and exosome-depleted serum. According to these preselections, serum-exosomes were tested by flow cytometry for the PaCa-initiating cell (PaCIC) markers CD44v6, Tspan8, EpCAM, MET and CD104. Serum-exosomes and exosome-depleted serum was tested for miR-1246, miR-4644, miR-3976 and miR-4306 recovery by qRT-PCR. The majority (95%) of patients with PaCa (131) and patients with nonPa-malignancies reacted with a panel of anti-CD44v6, -Tspan8, -EpCAM and -CD104. Serum-exosomes of healthy donors' and patients with nonmalignant diseases were not reactive. Recovery was tumor grading and staging independent including early stages. The selected miR-1246, miR-4644, miR-3976 and miR-4306 were significantly upregulated in 83% of PaCa serum-exosomes, but rarely in control groups. These miRNA were also elevated in exosome-depleted serum of patients with PaCa, but at a low level. Concomitant evaluation of PaCIC and miRNA serum-exosome marker panels significantly improved sensitivity (1.00, CI: 0.95-1) with a specificity of 0.80 (CI: 0.67-0.90) for PaCa versus all others groups and of 0.93 (CI: 0.81-0.98) excluding nonPa-malignancies. Thus, the concomitant evaluation of PaCIC and PaCa-related miRNA marker panels awaits retrospective analyses of larger cohorts, as it should allow for a highly sensitive, minimally-invasive PaCa diagnostics.

  2. Increasing the sensitivity of the spectrophotometric determinations of the oxygen content in YBCO superconducting samples using the I(3-)-starch compound.

    Science.gov (United States)

    Nedeltcheva, Tsvetanka K; Georgieva, Stela Iv; Vladimirova, Latinka K; Stoyanova-Ivanova, Angelina K

    2009-03-15

    The conditions for formation of the I(3)(-)-starch compound and measuring its absorbance have been found, and a spectrophotometric method has been developed for the determination of the oxygen content in YBa(2)Cu(3)O(y) superconducting bulk samples. The method involves the following stages: a decomposition of the sample in an acid medium in the presence of iodide ions under inert atmosphere; formation of a complex between Cu(II) and glycine; binding the I(3)(-)-complex with a starch and the absorbance measurement of the colored I(3)(-)-starch compound. The coefficient of the active oxygen is calculated by the ratio of the absorbances of two solutions and the method does not require both calibration and precise measuring sample mass. The accuracy of the results is confirmed applying the comparative spectrophotometric method that uses the yellow I(3)(-)-complex. The precision of the results evaluated by the relative standard deviation is 2%. The developed method is sensitive and allows a sample mass about 2mg to be used. The analysis is rapid and requires a simple and inexpensive apparatus. Thus the new method would be useful for an express analytical control of the oxygen content of YBCO-superconducting materials produced for the electronics.

  3. A nuclear mutant of Chlamydomonas that exhibits increased sensitivity to UV irradiation, reduced recombination of nuclear genes, and altered transmission of chloroplast genes.

    Science.gov (United States)

    Rosen, H; Newman, S M; Boynton, J E; Gillham, N W

    1991-01-01

    Meiotic progeny of Chlamydomonas reinhardtii normally receive chloroplast genomes only from the mt+ parent. However, exceptional zygotes, which transmit the chloroplast genomes of both parents or, more rarely, only those of the mt- parent, arise at a low frequency. Mutations at the mt(+)-linked mat-3 locus were found previously to elevate the transmission of chloroplast genomes from the mt- parent, resulting in a much higher than normal frequency of exceptional zygotes. In this paper we demonstrate that an ultraviolet-sensitive nuclear mutation mapping at the uvsE1 locus, which is unlinked to mating type, also promotes chloroplast genome transmission from the mt- parent. This mutant, which was previously shown to reduce recombination of nuclear genes in meiosis, acts synergistically with the mat-3-3 mutation to produce an extremely high frequency of exceptional zygotes. Through the use of restriction fragment length polymorphisms existing in the chloroplast genomes of C. reinhardtii and the interfertile strain C. smithii, we show that chloroplast DNA fragments from the mt- parent normally begin to disappear shortly after zygote formation. However, this process appears to be blocked totally in the absence of wild-type uvsE1 and mat-3 gene products. Our findings are consistent with the hypothesis that both gene products contribute to the mechanism responsible for uniparental inheritance of the chloroplast genome from the mt+ parent.

  4. Evaluate, assess, treat: development and evaluation of the EAT framework to increase effective communication regarding sensitive oral-systemic health issues.

    Science.gov (United States)

    DeBate, R D; Cragun, D; Gallentine, A A; Severson, H H; Shaw, T; Cantwell, C; Christiansen, S; Koerber, A; Hendricson, W; Tomar, S L; McCormack Brown, K; Tedesco, L A

    2012-11-01

    Oral healthcare providers are likely to encounter a number of sensitive oral/systemic health issues whilst interacting with patients. The purpose of the current study was to develop and evaluate a framework aimed at oral healthcare providers to engage in active secondary prevention of eating disorders (i.e. early detection of oral manifestations of disordered eating behaviours, patient approach and communication, patient-specific oral treatment, and referral to care) for patients presenting with signs of disordered eating behaviours. The EAT Framework was developed based on the Brief Motivational Interviewing (B-MI) conceptual framework and comprises three continuous steps: Evaluating, Assessing, and Treating. Using a group-randomized control design, 11 dental hygiene (DH) and seven dental (D) classes from eight institutions were randomized to either the intervention or control conditions. Both groups completed pre- and post-intervention assessments. Hierarchical linear models were conducted to measure the effects of the intervention whilst controlling for baseline levels. Statistically significant improvements from pre- to post-intervention were observed in the Intervention group compared with the Control group on knowledge of eating disorders and oral findings, skills-based knowledge, and self-efficacy (all P oral/systemic health issues. Because the EAT Framework was developed by translating B-MI principles and procedures, the framework can be easily adopted as a non-confrontational method for patient communication.

  5. Self-assembled TiO₂ with increased photoelectron production, and improved conduction and transfer: enhancing photovoltaic performance of dye-sensitized solar cells.

    Science.gov (United States)

    Ahmed, Saquib; Du Pasquier, Aurelien; Birnie, Dunbar P; Asefa, Tewodros

    2011-08-01

    Highly crystalline mesoporous anatase TiO(2) is prepared through supramolecular self-assembly and by utilizing cetyltrimethylammonium bromide (CTAB) as templating material. Photoanodes of dye-sensitized solar cells (DSSCs) made from these TiO(2) nanoparticles are found to have a high specific surface area of 153 m(2)/g and high surface roughness. Optical absorption spectroscopy studies reveal that the photoanode films adsorb four times more dye than films made of commercial P25 TiO(2). Mercury porosimetry and field emission scanning electron microscope (FESEM) studies show hierarchical macro- and meso-porosity of the photoanode films leading to better dye and electrolyte percolation, combined with improved electron conduction pathways compared to P25 films. Electrochemical impedance studies confirm lower impedance and higher electron lifetime in the synthesized mesoporous TiO(2) films compared to P25 films. Higher photovoltaic efficiency was recorded of cells made from the synthesized mesoporous TiO(2) in comparison to the corresponding cells made from P25. Incident-photon-to-current efficiency data provided critical understanding of recombination kinetics, and provided proof of Mie scattering by the self-assembled submicrometer sized TiO(2) aggregates and the macropores in their structure. The scattering phenomenon was further corroborated by diffused reflectance studies. An in-depth analysis of CTAB-templated mesoporous TiO(2) has been conducted to show how it can be a good candidate photoanode material for enhancing the performance of DSSCs.

  6. Four parameters increase the sensitivity and specificity of the exon array analysis and disclose 25 novel aberrantly spliced exons in myotonic dystrophy.

    Science.gov (United States)

    Yamashita, Yoshihiro; Matsuura, Tohru; Shinmi, Jun; Amakusa, Yoshinobu; Masuda, Akio; Ito, Mikako; Kinoshita, Masanobu; Furuya, Hirokazu; Abe, Koji; Ibi, Tohru; Sahashi, Ko; Sahashi, Koo; Ohno, Kinji

    2012-06-01

    Myotonic dystrophy type 1 (DM1) is an RNA gain-of-function disorder in which abnormally expanded CTG repeats of DMPK sequestrate a splicing trans-factor MBNL1 and upregulate another splicing trans-factor CUGBP1. To identify a diverse array of aberrantly spliced genes, we performed the exon array analysis of DM1 muscles. We analyzed 72 exons by RT-PCR and found that 27 were aberrantly spliced, whereas 45 were not. Among these, 25 were novel and especially splicing aberrations of LDB3 exon 4 and TTN exon 45 were unique to DM1. Retrospective analysis revealed that four parameters efficiently detect aberrantly spliced exons: (i) the signal intensity is high; (ii) the ratio of probe sets with reliable signal intensities (that is, detection above background P-value=0.000) is high within a gene; (iii) the splice index (SI) is high; and (iv) SI is deviated from SIs of the other exons that can be estimated by calculating the deviation value (DV). Application of the four parameters gave rise to a sensitivity of 77.8% and a specificity of 95.6% in our data set. We propose that calculation of DV, which is unique to our analysis, is of particular importance in analyzing the exon array data.

  7. Persistent gating deficit and increased sensitivity to NMDA receptor antagonism after puberty in a new mouse model of the human 22q11.2 microdeletion syndrome

    DEFF Research Database (Denmark)

    Didriksen, Michael; Fejgin, Kim; Nilsson, Simon R O;

    2016-01-01

    BACKGROUND: The hemizygous 22q11.2 microdeletion is a common copy number variant in humans. The deletion confers high risk for neurodevelopmental disorders, including autism and schizophrenia. Up to 41% of deletion carriers experience psychotic symptoms. METHODS: We present a new mouse model (Df...... displayed increased amplitude of loudness-dependent auditory evoked potentials. Prefrontal cortex and dorsal striatal elevations of the dopamine metabolite DOPAC and increased dorsal striatal expression of the AMPA receptor subunit GluR1 was found. The Df(h22q11)/+ mice did not deviate from wild-type mice...... conditions related to 22q11.2DS it is suggested to expose the Df(h22q11)/+ mice to environmental stressors that may unmask latent psychopathology. CONCLUSION: The Df(h22q11)/+ model will be a valuable tool for increasing our understanding of the etiology of schizophrenia and other psychiatric disorders...

  8. High sensitivity of embryo-larval stage of the Mediterranean mussel, Mytilus galloprovincialis to metal pollution in combination with temperature increase.

    Science.gov (United States)

    Boukadida, Khouloud; Banni, Mohamed; Gourves, Pierre-Yves; Cachot, Jérôme

    2016-12-01

    The present work aimed to assess the effects of two widespread metallic pollutants, copper and silver, along with environmentally-realistic temperature increases, on embryo-larval development of the Mediterranean mussel Mytilus galloprovincialis. First, mussel embryos upon fertilization were exposed for 48 h to increasing concentrations of Cu (0.5-500 μg/L) and Ag (0.1-100 μg/L) at different temperatures (18, 20, 22 or 24 °C) in order to characterize toxicity of each toxicant at the different tested temperatures. Increasing concentrations of a Cu-Ag mixture were then tested in order to assess the mixture effect at different temperatures (18, 20 or 22 °C). Embryotoxicity was measured after 48 h of exposure (D-larvae stage) considering both the percentage of abnormalities and developmental arrest in D-larvae. The results suggest that the optimum temperature for mussel larvae development is 18 °C (12.65± 1.6% malformations) and beyond 20 °C a steep increase of abnormal larvae was observed up to 100% at 24 °C. Ag was more toxic than Cu with a 50% effective concentration (EC50) at 18 °C of 6.58 μg/L and 17.6 μg/L, respectively. Temperature increased the toxicity of both metals as proved with the EC50 at 20 °C at 3.86 μg/L and 16.28 μg/L for Ag and Cu respectively. Toxic unit calculation suggests additive effects of Cu and Ag in mixture at 18 and 20 °C. These results highlight a possible impairment of M. galloprovincialis reproduction in the Mediterranean Sea in relation to increase of both pollutants and water temperature due to global warming.

  9. One versus five-days of exposure to varying concentrations of B100 soya biodiesel exhaust reveals a threshold concentration for increased sensitivity to aconitine-induced arrhythmia

    Science.gov (United States)

    Although biodiesel (BD) is rapidly being considered as an alternative to diesel fuel, its health effects have not been thoroughly characterized. We previously used the aconitine challenge test to demonstrate that a single exposure to petroleum diesel exhaust (DE) increases the ri...

  10. Study design for a randomized controlled trial to increase the relative reinforcing value of vegetable consumption using incentive sensitization among obese and overweight people

    Science.gov (United States)

    Federal dietary guidance recommends consumption of a variety of vegetables, but Americans only consume a small fraction of recommended amounts. Studies have attempted to increase consumption with modest results. In this manuscript, we present the protocol for a study that applies incentive sensitiza...

  11. Induction of NKG2D ligands and increased sensitivity of tumor cells to NK cell-mediated cytotoxicity by hematoporphyrin-based photodynamic therapy.

    Science.gov (United States)

    Park, Min-Ju; Bae, Jae-Ho; Chung, Joo Seop; Kim, Sun-Hee; Kang, Chi-Dug

    2011-01-01

    Natural killer (NK) cells are important innate effector cells which can irradicate tumor cells through specific interactions between activating receptors on NK cells and their cognate ligands on cancer cells. Recently, it has been known that induction of activating NKG2D ligands including MHC class I chain-related (MIC) and UL16-binding protein (ULBP) families on tumor cells by various stresses makes them more susceptible to NK cell-mediated cytotoxicity. Therefore, it was investigated whether sublethal dose of hematoporphyrin-based photodynamic therapy (PDT) could up-regulate NKG2D ligands on tumor cells and increase the susceptibility of cancer cells against NK cells. Treatment with sublethal dose of hematoporphyrin-based PDT increased mRNA transcription and surface expression of ULBP1 and ULBP2 genes in SNU-1 human gastric tumor cell line and MICA/B, ULBP1, ULBP2 and ULBP3 genes in SW-900 human lung cancer cell line. These results were followed by increased susceptibility of cancer cells to NK cell-mediated cytotoxicity after sublethal PDT, which was abolished by addition of a blocking NKG2D mAb. Therefore, it could be suggested that the effect of hematoporphyrin-based PDT might be mediated in part by the increased susceptibility to NK cells via induction of NKG2D ligands on tumor cells, which survived after treatment with PDT.

  12. Continuous fat oxidation in acetyl–CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity

    Science.gov (United States)

    Choi, Cheol Soo; Savage, David B.; Abu-Elheiga, Lutfi; Liu, Zhen-Xiang; Kim, Sheene; Kulkarni, Ameya; Distefano, Alberto; Hwang, Yu-Jin; Reznick, Richard M.; Codella, Roberto; Zhang, Dongyan; Cline, Gary W.; Wakil, Salih J.; Shulman, Gerald I.

    2007-01-01

    Acetyl–CoA carboxylase 2 (ACC)2 is a key regulator of mitochondrial fat oxidation. To examine the impact of ACC2 deletion on whole-body energy metabolism, we measured changes in substrate oxidation and total energy expenditure in Acc2−/− and WT control mice fed either regular or high-fat diets. To determine insulin action in vivo, we also measured whole-body insulin-stimulated liver and muscle glucose metabolism during a hyperinsulinemic–euglycemic clamp in Acc2−/− and WT control mice fed a high-fat diet. Contrary to previous studies that have suggested that increased fat oxidation might result in lower glucose oxidation, both fat and carbohydrate oxidation were simultaneously increased in Acc2−/− mice. This increase in both fat and carbohydrate oxidation resulted in an increase in total energy expenditure, reductions in fat and lean body mass and prevention from diet-induced obesity. Furthermore, Acc2−/− mice were protected from fat-induced peripheral and hepatic insulin resistance. These improvements in insulin-stimulated glucose metabolism were associated with reduced diacylglycerol content in muscle and liver, decreased PKCθ activity in muscle and PKCε activity in liver, and increased insulin-stimulated Akt2 activity in these tissues. Taken together with previous work demonstrating that Acc2−/− mice have a normal lifespan, these data suggest that Acc2 inhibition is a viable therapeutic option for the treatment of obesity and type 2 diabetes. PMID:17923673

  13. Increased electrocatalyzed performance through hairpin oligonucleotide aptamer-functionalized gold nanorods labels and graphene-streptavidin nanomatrix: Highly selective and sensitive electrochemical biosensor of carcinoembryonic antigen.

    Science.gov (United States)

    Wen, Wei; Huang, Jing-Yi; Bao, Ting; Zhou, Jun; Xia, Hong-Xing; Zhang, Xiu-Hua; Wang, Sheng-Fu; Zhao, Yuan-Di

    2016-09-15

    We report a triplex signal amplification strategy for sensitive biosensing of cancer biomarker by taking advantage of hairpin-shaped oligonucleotide-functionalized gold nanorods (HO-GNRs), graphene and the avidin-biotin reation. The strategy expands electrochemical detection of carcinoembryonic antigen (CEA) by using an aptamer as biosensor's recognition element and HO-GNRs as signal enhancer. To construct this biosensor, the GNR was used as a carrier of horseradish peroxidase (HRP) and HO aptamer with a biotin at the 3'-end and a thiol at the 5'-end, which amplified the electrochemical response because of a large molar ratio of HRP to HO. In the presence of target CEA, the binding reactions of CEA with the loop portions of the HOs caused HOs' loop-stem structure opened and exposed the biotins, and then HRP-GNRs-HO conjugates were captured on graphene and streptavidin modified electrodes via the reaction between the exposed biotins and preimmobilized streptavidins. The accumulation of HRP effectively catalyzed the hydrogen peroxide-mediated oxidation of o-phenylenediamine to generate an electrochemical reduction current for CEA detection. Under optimal conditions, the electrochemical biosensor exhibited a wide dynamic range of 5pgmL(-1) and 50ngmL(-1) toward CEA standards with a low detection limit of 1.5pgmL(-1) (signal-to-noise ratio of 3). The proposed biosensor accurately detected CEA concentration in 8 human serum samples from patients with lung diseases, showing excellent correlations with standard chemiluminescence immunoassay. Furthermore, these results of target DNA detection made it abundantly clear that the proposed strategy can also be extended for detection of other relative biomarkers using different functional DNA structures, which shows great prospects in single-nucleotide polymorphisms analysis, biomedical sensing and application for accurate clinical diseases diagnostic.

  14. Multi-scale enhancement of climate prediction over land by increasing the model sensitivity to vegetation variability in EC-Earth

    Science.gov (United States)

    Alessandri, Andrea; Catalano, Franco; De Felice, Matteo; Van Den Hurk, Bart; Doblas Reyes, Francisco; Boussetta, Souhail; Balsamo, Gianpaolo; Miller, Paul A.

    2016-10-01

    The EC-Earth earth system model has been recently developed to include the dynamics of vegetation. In its original formulation, vegetation variability is simply operated by the Leaf Area Index (LAI), which affects climate basically by changing the vegetation physiological resistance to evapotranspiration. This coupling has been found to have only a weak effect on the surface climate modeled by EC-Earth. In reality, the effective sub-grid vegetation fractional coverage will vary seasonally and at interannual time-scales in response to leaf-canopy growth, phenology and senescence. Therefore it affects biophysical parameters such as the albedo, surface roughness and soil field capacity. To adequately represent this effect in EC-Earth, we included an exponential dependence of the vegetation cover on the LAI. By comparing two sets of simulations performed with and without the new variable fractional-coverage parameterization, spanning from centennial (twentieth century) simulations and retrospective predictions to the decadal (5-years), seasonal and weather time-scales, we show for the first time a significant multi-scale enhancement of vegetation impacts in climate simulation and prediction over land. Particularly large effects at multiple time scales are shown over boreal winter middle-to-high latitudes over Canada, West US, Eastern Europe, Russia and eastern Siberia due to the implemented time-varying shadowing effect by tree-vegetation on snow surfaces. Over Northern Hemisphere boreal forest regions the improved representation of vegetation cover tends to correct the winter warm biases, improves the climate change sensitivity, the decadal potential predictability as well as the skill of forecasts at seasonal and weather time-scales. Significant improvements of the prediction of 2 m temperature and rainfall are also shown over transitional land surface hot spots. Both the potential predictability at decadal time-scale and seasonal-forecasts skill are enhanced over

  15. Multi-scale enhancement of climate prediction over land by increasing the model sensitivity to vegetation variability in EC-Earth

    Science.gov (United States)

    Alessandri, Andrea; Catalano, Franco; De Felice, Matteo; Van Den Hurk, Bart; Doblas Reyes, Francisco; Boussetta, Souhail; Balsamo, Gianpaolo; Miller, Paul

    2016-04-01

    The EC-Earth earth system model has been recently developed to include the dynamics of vegetation. In its original formulation, vegetation variability is simply operated by the Leaf Area Index (LAI), which affects climate basically by changing the vegetation physiological resistance to evapotranspiration. This coupling has been found to have only a weak effect on the surface climate modeled by EC-Earth. In reality, the effective sub-grid vegetation fractional coverage will vary seasonally and at interannual time-scales in response to leaf-canopy growth, phenology and senescence. Therefore it affects biophysical parameters such as the albedo, surface roughness and soil field capacity. To adequately represent this effect in EC-Earth, we included an exponential dependence of the vegetation cover on the LAI. By comparing two sets of simulations performed with and without the new variable fractional-coverage parameterization, spanning retrospective predictions at the decadal (5-years), seasonal and sub-seasonal time-scales, we show for the first time a significant multi-scale enhancement of vegetation impacts in climate simulation and prediction over land. Particularly large effects at multiple time scales are shown over boreal winter middle-to-high latitudes over Canada, West US, Eastern Europe, Russia and eastern Siberia due to the implemented time-varying shadowing effect by tree-vegetation on snow surfaces. Over Northern Hemisphere boreal forest regions the improved representation of vegetation cover tends to correct the winter warm biases, improves the climate change sensitivity, the decadal potential predictability as well as the skill of forecasts at seasonal and sub-seasonal time-scales. Significant improvements of the prediction of 2m temperature and rainfall are also shown over transitional land surface hot spots. Both the potential predictability at decadal time-scale and seasonal-forecasts skill are enhanced over Sahel, North American Great Plains, Nordeste

  16. Schizophrenia, amphetamine-induced sensitized state and acute amphetamine exposure all show a common alteration: increased dopamine D2 receptor dimerization

    Directory of Open Access Journals (Sweden)

    Wang Min

    2010-09-01

    Full Text Available Abstract Background All antipsychotics work via dopamine D2 receptors (D2Rs, suggesting a critical role for D2Rs in psychosis; however, there is little evidence for a change in receptor number or pharmacological nature of D2Rs. Recent data suggest that D2Rs form dimers in-vitro and in-vivo, and we hypothesized that schizophrenia, as well as preclinical models of schizophrenia, would demonstrate altered dimerization of D2Rs, even though the overall number of D2Rs was unaltered. Methods We measured the expression of D2Rs dimers and monomers in patients with schizophrenia using Western blots, and then in striatal tissue from rats exhibiting the amphetamine-induced sensitized state (AISS. We further examined the interaction between D2Rs and the dopamine transporter (DAT by co-immunoprecipitation, and measured the expression of dopamine D2High receptors with ligand binding assays in rat striatum slices with or without acute amphetamine pre-treatment. Results We observed significantly enhanced expression of D2Rs dimers (277.7 ± 33.6% and decreased expression of D2Rs monomers in post-mortem striatal tissue of schizophrenia patients. We found that amphetamine facilitated D2Rs dimerization in both the striatum of AISS rats and in rat striatal neurons. Furthermore, amphetamine-induced D2Rs dimerization may be associated with the D2R-DAT protein-protein interaction as an interfering peptide that disrupts the D2R-DAT coupling, blocked amphetamine-induced up-regulation of D2Rs dimerization. Conclusions Given the fact that amphetamine induces psychosis and that the AISS rat is a widely accepted animal model of psychosis, our data suggest that D2R dimerization may be important in the pathophysiology of schizophrenia and may be a promising new target for novel antipsychotic drugs.

  17. Over-expression of ascorbate oxidase in the apoplast of transgenic tobacco results in altered ascorbate and glutathione redox states and increased sensitivity to ozone

    DEFF Research Database (Denmark)

    Sanmartin, Maite; Drogoudi, Pavlina D.; Lyons, Tom

    2003-01-01

    Transgenic tobacco (Nicotiana tabacum L. cv. Xanthi) plants expressing cucumber ascorbate oxidase (EC.1.10.3.3) were used to examine the role of extracellular ascorbic acid in mediating tolerance to the ubiquitous air pollutant, ozone (O3). Three homozygous transgenic lines, chosen on the basis...... of a preliminary screen of AO activity in the leaves of 29 lines, revealed up to a 380-fold increase in AO activity, with expression predominantly associated with leaf cell walls. Overexpression of AO resulted in no change in the total ascorbate content recovered in apoplast washing fluid, but the redox state...... of ascorbate was reduced from 30% in wild-type leaves to below the threshold for detection in transgenic plants. Levels of ascorbic acid and glutathione in the symplast were not affected by AO overexpression, but the redox state of ascorbate was reduced, while that of glutathione was increased. AO...

  18. Noscapine Increases the Sensitivity of Drug-Resistant Ovarian Cancer Cell Line SKOV3/DDP to Cisplatin by Regulating Cell Cycle and Activating Apoptotic Pathways.

    Science.gov (United States)

    Shen, Wei; Liang, Bingfeng; Yin, Jie; Li, Xiurong; Cheng, Jianxin

    2015-05-01

    Cisplatin is a first-line chemotherapy drug against ovarian cancer. However, its strong toxic side effects and the development of cisplatin resistance in human cancer cells seriously influence the effects of chemotherapy and quality of life in patients. Noscapine (Nos), a non-toxic benzylisoquinoline alkaloid extracted from opium, has been recently reported to have anti-cancer activity, but the mechanism of that effect has not been clearly established. In the present study, we investigated cytotoxicity of Nos in combination with cisplatin (DDP) in drug-resistant human ovarian cancer cell line SKOV3/DDP in vitro and in vivo null mice xenograft model. Cell proliferation was measured by MTT assay, flow cytometry was used to analyze cell cycle and apoptosis, protein expression of several apoptotic factors was investigated by flow cytometry and immunohistochemical method, and their mRNA expression levels were determined by real-time PCR. In vitro experiments showed that Nos significantly inhibited proliferation of SKOV3/DDP cells. DDP/Nos-combined treatment notably enhanced DDP-induced inhibition of cell proliferation and increased the pro-apoptotic effect of DDP in SKOV3/DDP cells. DDP/Nos administration increased the proportion of G2/M cells, reduced both protein and mRNA expression of anti-apoptotic factors XIAP, surviving and NF-kB, and augmented protein and mRNA levels of pro-apoptotic caspase-3. In vivo experiments revealed that Nos/DDP treatment increased the apoptotic rate of xenograft tumors in null mice. Tumor volume decreased from 1.733 ± 0.155 g in mice treated with DDP alone to 1.191 ± 0.106 g in animals treated with Nos/DDP. These observations suggest that Nos increases the anti-cancer activity of DDP against the drug-resistant ovarian cancer cell line SKOV3/DDP by modulating the cell cycle and activating apoptotic pathways. The study provides a new chemotherapy strategy for the treatment of DDP-resistant human ovarian cancer.

  19. The defective phosphoribosyl diphosphate synthase in a temperature-sensitive prs-2 mutant of Escherichia coli is compensated by increased enzyme synthesis

    DEFF Research Database (Denmark)

    Post, David A.; Switzer, Robert L.; Hove-Jensen, Bjarne

    1996-01-01

    at 25 degrees C. The mutant enzyme had nearly normal heat stability, as long as it was synthesized at 25 degrees C. In contrast, there was hardly any PRPP synthase activity or anti-PRPP synthase antibody cross-reactive material present in cells harbouring the glycine to serine alteration following...... synthase activity as a strain harbouring a plasmid-borne wild-type prs allele. In cells harbouring both mutations, the C -> T mutation appeared to compensate for the G -> A mutation by increasing the amount of a partially defective enzyme at the permissive temperature....

  20. Human serum levels of fetal antigen 1 (FA1/Dlk1) increase with obesity, are negatively associated with insulin sensitivity and modulate inflammation in vitro

    DEFF Research Database (Denmark)

    Chacón, M R; Miranda, M; Jensen, C H

    2008-01-01

    chemoattractant protein-1 (MCP-1), IL-6 (interleukin-6) and adiponectin). CONCLUSION: FA1 serum levels were increased in obese subjects and might influence S(i). The stimulatory effect of FA1 protein on pro-inflammatory cytokines on both immune and adipose cell types could contribute to worsening the inflammatory...... levels. In severe obesity, serum levels of FA1 decreased 1.4-fold 6 months after bariatric surgery. In vitro assays with FA1 protein on human monocytes and adipocytes cell lines modified the expression of pro-inflammatory cytokines and adipokines (tumor necrosis factor-alpha (TNFalpha), monocyte...

  1. Intramyocellular lipid content and insulin sensitivity are increased following a short-term low-glycemic index diet and exercise intervention

    DEFF Research Database (Denmark)

    Haus, Jacob M; Solomon, Thomas; Lu, Lan

    2011-01-01

    The relationship between intramyocellular (IMCL) and extramyocellular lipid (EMCL) accumulation and skeletal muscle insulin resistance is complex and dynamic. We examined the effect of a short-term (7-day) low-glycemic index (LGI) diet and aerobic exercise training intervention (EX) on IMCL...... in FPI (r = -0.78, P = 0.002) and HOMA-IR (r = -0.61, P = 0.03). These data suggest that increases in the IMCL pool following a low glycemic diet and exercise intervention may represent lipid repartitioning from EMCL. The lower systemic glucose levels that prevail while eating a low glycemic diet may...

  2. CpG-ODN 7909 increases radiation sensitivity of radiation-resistant human lung adenocarcinoma cell line by overexpression of Toll-like receptor 9.

    Science.gov (United States)

    Yan, Li; Xu, Guoxiong; Qiao, Tiankui; Chen, Wei; Yuan, Sujuan; Li, Xuan

    2013-09-01

    Radioresistance is one of the main reasons for the failure of radiotherapy in lung cancer. The aim of this study was to establish a radiation-resistant lung cancer cell line, to evaluate whether CpG oligodeoxyribonucleotide (CpG-ODN) 7909 could increase its radiosensitivity and to explore the relevant mechanisms. The radioresistant cell line, referred to as R-A549, was generated by reduplicative fractionated irradiation from the human lung adenocarcinoma cell line A549. The radioresistance of R-A549 cells were confirmed by the Cell Counting Kit-8 (CCK-8), cell viability assay, and clonogenic assay. Cell growth kinetics, morphological feature, and radiosensitivity were compared between the original A549 cells and R-A549 cells treated with or without CpG-ODN 7909 or radiation. To further explore the potential mechanisms of radiosensitivity, the cell cycle distributions and the expression of Toll-like receptor 9 (TLR-9) were examined by Western blot and flow cytometry. The R-A549 cell line was generated and its radioresistance was further confirmed. CpG-ODN 7909 was found to increase much more radiosensitivity of R-A549 cells under combined treatments with CpG-ODN 7909 and radiation compared with its control group without any treatments. They presented their respective D0 1.33 ± 0.20 Gy versus 1.76 ± 0.25 Gy with N 3.44 ± 1.01 versus 4.96 ± 0.32. Further, there was a larger cell population of R-A549 cells under combined treatment in the G2/M phase compared with the control group after treatment with CpG-ODN7909 or radiation alone at 24 and 48 hour. The expression level of TLR-9 in R-A549 cells was found higher than in A549 cells. These results suggested that CpG-ODN 7909 increased the radiosensitivity of R-A549 cells, which might be mediated via the upregulated TLR-9 and prolonged cell cycle arrest in the G2/M phase compared with A549 cells.

  3. Increases in doxorubicin sensitivity and radioiodide uptake by transfecting shMDR and sodium/iodide symporter gene in cancer cells expressing multidrug resistance

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Sohn Joo; Lee, Yong Jin; Lee, You La; Choi, Chang Ik; Lee, Sang Woo; Yoo, Jeong Soo; Ahn, Byeong Cheol; Lee, In Kyu; Lee, Jae Tae [Kyungpook National University, Daegu (Korea, Republic of)

    2007-06-15

    Multidrug resistance (MDR) of the cancer cells related to mdr1 gene expression can be effectively treated by selective short hairpin RNA for mdr1 gene (shMDR). Sodium/iodide symporter (NIS) gene is well known to have both reporter and therapeutic gene characteristics. We have co-transfected both shMDR and NIS gene into colon cancer cells (HCT15 cell) expressing MDR and Tc-99m sestamibi and I-125 uptake were measured. In addition, cytotoxic effects of doxorubicin and I-131 therapy were also assessed after transfection. At first, shMDR was transfected with liposome reagent into human embryonic kidney cells (HEK293) and HCT cells. shMDR transfection was confirmed by RT-PCR and western blot analysis. Adenovirus expressing NIS (Ad-NIS) gene and shMDR (Ad-shMDR) were co-transfected with Ad-NIS into HCT15 cells. Forty-eight hours after infection, inhibition of P-gycoprotein (Pgp) function by shMDR was analyzed by a change of Tc-99m sestamibi uptake and doxorubicin cytotoxicity, and functional activity of induced NIS gene expression was assessed with I-125 uptake assay. In HEK293 cells transfected with shMDR, mdr1 mRNA and Pgp protein expressions were down regulated. HCT15 cells infected with 20 MOI of Ad-NIS was higher NIS protein expression than control cells. After transfection of 300 MOI of Ad-shMDR either with or without 10 MOI of Ad-NIS, uptake of Tc-99m sestamibi increased up to 1.5-fold than control cells. HCT15 cells infected with 10 MOI of Ad-NIS showed approximately 25-fold higher I-125 uptake than control cells. Cotransfection of Ad-shMDR and Ad-NIS resulted in enhanced cytotoxic by doxorubicin in HCT15 cells. I-131 treatment on HCT15 cells infected with 20 MOI of Ad-NIS revealed increased cytotoxic effect. Suppression of mdr1 gene expression, retention of Tc-99m sestamibi, enhanced doxorubicin cytotoxicity and increases in I-125 uptake were achieved in MDR expressing cancer cell by co-transfection of shMDR and NIS gene. Dual therapy with doxorubicin and

  4. Does examination of fecal samples 24 hours after cestocide treatment increase the sensitivity of Anoplocephala spp. detection in naturally infected horses?

    Science.gov (United States)

    Elsener, Johanne; Villeneuve, Alain

    2011-02-01

    Fecal samples were examined immediately before and 24 to 48 h after cestocide treatment for a comparative detection of tapeworm-positive horses. In early winter, 17 weanlings, 20 yearlings, 15 2-year-old horses, 24 breeding mares, and 2 stallions were treated with praziquantel in combination with a macrocyclic lactone. The horses were presumed to be naturally infected with tapeworms after pasture grazing. Fecal samples were collected before treatment (Day 0), at 24 or 48 h after treatment (Day 1-2), and 16 to 21 d after treatment (Day 16-21). A Wisconsin test was done on all fecal samples. Odds of detection of infection for all age groups increased by a factor of 2.04 [95% confidence interval (CI): 1.30 to 3.20] from Day 0 to Day 1-2 (P = 0.002).

  5. Long Withdrawal of Methylphenidate Induces a Differential Response of the Dopaminergic System and Increases Sensitivity to Cocaine in the Prefrontal Cortex of Spontaneously Hypertensive Rats.

    Directory of Open Access Journals (Sweden)

    Maurício dos Santos Pereira

    Full Text Available Methylphenidate (MPD is one of the most prescribed drugs for alleviating the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD. However, changes in the molecular mechanisms related to MPD withdrawal and susceptibility to consumption of other psychostimulants in normal individuals or individuals with ADHD phenotype are not completely understood. The aims of the present study were: (i to characterize the molecular differences in the prefrontal dopaminergic system of SHR and Wistar strains, (ii to establish the neurochemical consequences of short- (24 hours and long-term (10 days MPD withdrawal after a subchronic treatment (30 days with Ritalin® (Methylphenidate Hydrochloride; 2.5 mg/kg orally, (iii to investigate the dopaminergic synaptic functionality after a cocaine challenge in adult MPD-withdrawn SHR and Wistar rats. Our results indicate that SHR rats present reduced [3H]-Dopamine uptake and cAMP accumulation in the prefrontal cortex (PFC and are not responsive to dopaminergic stimuli in when compared to Wistar rats. After a 24-hour withdrawal of MPD, SHR did not present any alterations in [3H]-Dopamine Uptake, [3H]-SCH 23390 binding and cAMP production; nonetheless, after a 10-day MPD withdrawal, the results showed a significant increase of [3H]-Dopamine uptake, of the quantity of [3H]-SCH 23390 binding sites and of cAMP levels in these animals. Finally, SHR that underwent a 10-day MPD withdrawal and were challenged with cocaine (10 mg/kg i.p. presented reduced [3H]-Dopamine uptake and increased cAMP production. Wistar rats were affected by the 10-day withdrawal of MPD in [3H]-dopamine uptake but not in cAMP accumulation; in addition, cocaine was unable to induce significant modifications in [3H]-dopamine uptake and in cAMP levels after the 10-day withdrawal of MPD. These results indicate a mechanism that could explain the high comorbidity between ADHD adolescent patients under methylphenidate treatment and substance abuse in adult

  6. Long Withdrawal of Methylphenidate Induces a Differential Response of the Dopaminergic System and Increases Sensitivity to Cocaine in the Prefrontal Cortex of Spontaneously Hypertensive Rats

    Science.gov (United States)

    dos Santos Pereira, Maurício; Sathler, Matheus Figueiredo; Valli, Thais da Rosa; Marques, Richard Souza; Ventura, Ana Lucia Marques; Peccinalli, Ney Ronner; Fraga, Mabel Carneiro; Manhães, Alex C.; Kubrusly, Regina

    2015-01-01

    Methylphenidate (MPD) is one of the most prescribed drugs for alleviating the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD). However, changes in the molecular mechanisms related to MPD withdrawal and susceptibility to consumption of other psychostimulants in normal individuals or individuals with ADHD phenotype are not completely understood. The aims of the present study were: (i) to characterize the molecular differences in the prefrontal dopaminergic system of SHR and Wistar strains, (ii) to establish the neurochemical consequences of short- (24 hours) and long-term (10 days) MPD withdrawal after a subchronic treatment (30 days) with Ritalin® (Methylphenidate Hydrochloride; 2.5 mg/kg orally), (iii) to investigate the dopaminergic synaptic functionality after a cocaine challenge in adult MPD-withdrawn SHR and Wistar rats. Our results indicate that SHR rats present reduced [3H]-Dopamine uptake and cAMP accumulation in the prefrontal cortex (PFC) and are not responsive to dopaminergic stimuli in when compared to Wistar rats. After a 24-hour withdrawal of MPD, SHR did not present any alterations in [3H]-Dopamine Uptake, [3H]-SCH 23390 binding and cAMP production; nonetheless, after a 10-day MPD withdrawal, the results showed a significant increase of [3H]-Dopamine uptake, of the quantity of [3H]-SCH 23390 binding sites and of cAMP levels in these animals. Finally, SHR that underwent a 10-day MPD withdrawal and were challenged with cocaine (10 mg/kg i.p.) presented reduced [3H]-Dopamine uptake and increased cAMP production. Wistar rats were affected by the 10-day withdrawal of MPD in [3H]-dopamine uptake but not in cAMP accumulation; in addition, cocaine was unable to induce significant modifications in [3H]-dopamine uptake and in cAMP levels after the 10-day withdrawal of MPD. These results indicate a mechanism that could explain the high comorbidity between ADHD adolescent patients under methylphenidate treatment and substance abuse in adult life

  7. Long Withdrawal of Methylphenidate Induces a Differential Response of the Dopaminergic System and Increases Sensitivity to Cocaine in the Prefrontal Cortex of Spontaneously Hypertensive Rats.

    Science.gov (United States)

    dos Santos Pereira, Maurício; Sathler, Matheus Figueiredo; Valli, Thais da Rosa; Marques, Richard Souza; Ventura, Ana Lucia Marques; Peccinalli, Ney Ronner; Fraga, Mabel Carneiro; Manhães, Alex C; Kubrusly, Regina

    2015-01-01

    Methylphenidate (MPD) is one of the most prescribed drugs for alleviating the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD). However, changes in the molecular mechanisms related to MPD withdrawal and susceptibility to consumption of other psychostimulants in normal individuals or individuals with ADHD phenotype are not completely understood. The aims of the present study were: (i) to characterize the molecular differences in the prefrontal dopaminergic system of SHR and Wistar strains, (ii) to establish the neurochemical consequences of short- (24 hours) and long-term (10 days) MPD withdrawal after a subchronic treatment (30 days) with Ritalin® (Methylphenidate Hydrochloride; 2.5 mg/kg orally), (iii) to investigate the dopaminergic synaptic functionality after a cocaine challenge in adult MPD-withdrawn SHR and Wistar rats. Our results indicate that SHR rats present reduced [3H]-Dopamine uptake and cAMP accumulation in the prefrontal cortex (PFC) and are not responsive to dopaminergic stimuli in when compared to Wistar rats. After a 24-hour withdrawal of MPD, SHR did not present any alterations in [3H]-Dopamine Uptake, [3H]-SCH 23390 binding and cAMP production; nonetheless, after a 10-day MPD withdrawal, the results showed a significant increase of [3H]-Dopamine uptake, of the quantity of [3H]-SCH 23390 binding sites and of cAMP levels in these animals. Finally, SHR that underwent a 10-day MPD withdrawal and were challenged with cocaine (10 mg/kg i.p.) presented reduced [3H]-Dopamine uptake and increased cAMP production. Wistar rats were affected by the 10-day withdrawal of MPD in [3H]-dopamine uptake but not in cAMP accumulation; in addition, cocaine was unable to induce significant modifications in [3H]-dopamine uptake and in cAMP levels after the 10-day withdrawal of MPD. These results indicate a mechanism that could explain the high comorbidity between ADHD adolescent patients under methylphenidate treatment and substance abuse in adult life.

  8. Post-trial dopaminergic modulation of conditioned catalepsy: A single apomorphine induced increase/decrease in dopaminergic activation immediately following a conditioned catalepsy response can reverse/enhance a haloperidol conditioned and sensitized catalepsy response.

    Science.gov (United States)

    Oliveira, Lucas Rangel; Dias, Flávia Regina Cruz; Santos, Breno Garone; Silva, Jade Leal Loureiro; Carey, Robert J; Carrera, Marinete Pinheiro

    2016-09-15

    Haloperidol can induce catalepsy and this drug effect can be conditioned as well as sensitized to contextual cues. We used a paired/unpaired Pavlovian conditioning protocol to establish haloperidol catalepsy conditioned and sensitized responses. Groups of rats were given 10 daily catalepsy tests following administration of vehicle (n=24) or haloperidol (1.0mg/kg) either paired (n=18) or unpaired (n=18) to testing. Subsequently, testing for conditioning was conducted and conditioning and sensitization of catalepsy were observed selectively in the paired group. Immediately following a second test for catalepsy conditioning, the groups were subdivided into 4 vehicle groups, 3 unpaired haloperidol groups and 3 paired haloperidol groups and were given one of three post-trial treatments (vehicle, 0.05mg/kg or 2.0mg/kg apomorphine). One day later the conditioned catalepsy test 3 was carried out and on the next day, a haloperidol challenge test was performed. The post-trial apomorphine treatments had major effects on the paired groups upon both conditioning and the haloperidol challenge test. The low dose apomorphine post-trial treatment enhanced both the conditioned and the haloperidol sensitized catalepsy responses. The high dose apomorphine post-trial treatment eliminated conditioned catalepsy and eliminated the initial acute catalepsy response to haloperidol that was induced in the vehicle control groups. These results demonstrate the sensitivity of conditioned drug cues to modification by increases/decreases in activity of the dopamine system in the immediate post-trial interval after a conditioning trial. This demonstration that post-trial dopaminergic drug treatments can modify conditioned drug behavior has broad implications for conditioned drug effects.

  9. The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors

    Directory of Open Access Journals (Sweden)

    Martín-García Julio

    2008-10-01

    Full Text Available Abstract Background HIV-1 infects macrophages and microglia in the brain and can cause neurological disorders in infected patients. We and others have shown that brain-derived envelope glycoproteins (Env have lower CD4 dependence and higher avidity for CD4 than those from peripheral isolates, and we have also observed increased fusogenicity and reduced sensitivity to the fusion inhibitor T-1249. Due to the genetic differences between brain and spleen env from one individual throughout gp120 and in gp41's heptad repeat 2 (HR2, we investigated the viral determinants for the phenotypic differences by performing functional studies with chimeric and mutant Env. Results Chimeric Env showed that the V1/V2-C2-V3 region in brain's gp120 determines the low CD4 dependence and high avidity for CD4, as well as macrophage tropism and reduced sensitivity to the small molecule BMS-378806. Changes in brain gp41's HR2 region did not contribute to the increased fusogenicity or to the reduced sensitivity to T-1249, since a T-1249-based peptide containing residues found in brain's but not in spleen's HR2 had similar potency than T-1249 and interacted similarly with an immobilized heptad repeat 1-derived peptide in surface plasmon resonance analysis. However, the increased fusogenicity and reduced T-1249 sensitivity of brain and certain chimeric Env mostly correlated with the low CD4 dependence and high avidity for CD4 determined by brain's V1-V3 region. Remarkably, most but not all of these low CD4-dependent, macrophage tropic envelopes glycoproteins also had increased sensitivity to the novel allosteric entry inhibitor HNG-105. The gp120's C2 region asparagine 283 (N283 has been previously associated with macrophage tropism, brain infection, lower CD4 dependence and higher CD4 affinity. Therefore, we introduced the N283T mutation into an env clone from a brain-derived isolate and into a brain tissue-derived env clone, and the T283N change into a spleen-derived env

  10. Increased environmental sensitivity in high mathematics performance

    NARCIS (Netherlands)

    Schwabe, I.; Boomsma, D.I.; Berg, van den S.M.

    2017-01-01

    Results of international comparisons of students in studies such as PISA (Program for International Student Assessment) and TIMSS (Trends in International Mathematics and Science Study) are often taken to indicate that mathematical education in Dutch schools is not appropriate for mathematically tal

  11. Decrease of D2 receptor binding but increase in D2-stimulated G-protein activation, dopamine transporter binding and behavioural sensitization in brains of mice treated with a chronic escalating dose 'binge' cocaine administration paradigm.

    Science.gov (United States)

    Bailey, A; Metaxas, A; Yoo, J H; McGee, T; Kitchen, I

    2008-08-01

    Understanding the neurobiology of the transition from initial drug use to excessive drug use has been a challenge in drug addiction. We examined the effect of chronic 'binge' escalating dose cocaine administration, which mimics human compulsive drug use, on behavioural responses and the dopaminergic system of mice and compared it with a chronic steady dose (3 x 15 mg/kg/day) 'binge' cocaine administration paradigm. Male C57BL/6J mice were injected with saline or cocaine in an escalating dose paradigm for 14 days. Locomotor and stereotypy activity were measured and quantitative autoradiographic mapping of D(1) and D(2) receptors, dopamine transporters and D(2)-stimulated [(35)S]GTPgammaS binding was performed in the brains of mice treated with this escalating and steady dose paradigm. An initial sensitization to the locomotor effects of cocaine followed by a dose-dependent increase in the duration of the locomotor effect of cocaine was observed in the escalating but not the steady dose paradigm. Sensitization to the stereotypy effect of cocaine and an increase in cocaine-induced stereotypy score was observed from 3 x 20 to 3 x 25 mg/kg/day cocaine. There was a significant decrease in D(2) receptor density, but an increase in D(2)-stimulated G-protein activity and dopamine transporter density in the striatum of cocaine-treated mice, which was not observed in our steady dose paradigm. Our results document that chronic 'binge' escalating dose cocaine treatment triggers profound behavioural and neurochemical changes in the dopaminergic system, which might underlie the transition from drug use to compulsive drug use associated with addiction, which is a process of escalation.

  12. A New Baroreceptor Sensitivity-Restoring Ca-Channel Blocker Diminishes Age-Related Morning Blood Pressure Increase in Hypertensive Patients: Open-Label Monitoring of Azelnidipine Treatment for Hypertension in the Early Morning (At-HOME Study

    Directory of Open Access Journals (Sweden)

    Mitsunori Sugiyama

    2010-01-01

    Full Text Available Background: Morning blood pressure (BP surge, which exhibits an age-related increase, is a risk factor for stroke in elderly hypertensive patients, independently of the 24-h BP level. We studied the effect of the new baroreceptor sensitivity (BRS-restoring Ca-channel blocker (CCB azelnidipine (AZ on this age-related morning BP increase. Methods: We conducted a 16-week prospective study to clarify the effect of morning dosing of AZ on home BPs measured in the morning and in the evening in 2,546 hypertensive patients (mean age, 65.1 years; female, 53.6%. Results: At baseline, ME-Dif (morning systolic BP [SBP]–evening SBP increased with age, independently of ME-Ave (average of the morning and evening SBPs. This age-related increase of ME-Dif was exaggerated by regular alcohol drinking and beta-blocker use. After AZ treatment (14.3 ± 3.6 mg/day, ME-AV and ME-Dif were significantly reduced independently of each other, with reductions of –18.1 ± 15.6 and –2.5 ± 13.2 mmHg, respectively (both p < 0.001. AZ treatment decreased age-related increase in ME-Dif particularly in patients who were regular consumers of alcohol and in beta-blocker users. Conclusions: The new BRS-restoring CCB AZ significantly reduced age-related increase in morning BP and had some potential benefit on cardiovascular protection in hypertension, particularly in elderly patients and/or consumers of alcohol.

  13. Sensitivity analysis

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003741.htm Sensitivity analysis To use the sharing features on this page, please enable JavaScript. Sensitivity analysis determines the effectiveness of antibiotics against microorganisms (germs) ...

  14. Circulating complement-C1q TNF-related protein 1 levels are increased in patients with type 2 diabetes and are associated with insulin sensitivity in Chinese subjects.

    Directory of Open Access Journals (Sweden)

    Xuebo Pan

    Full Text Available BACKGROUND: Complement-C1q TNF-related protein 1 (CTRP1, a member of the CTRP superfamily, possesses anti-inflammatory and anti-diabetic effects in mice. However, the clinical relevance of CTRP1 has been seldom explored. The current study aimed to investigate the association of circulating CTRP1 and type 2 diabetes mellitus (T2DM in a Chinese population. DESIGN AND METHODS: Serum CTRP1 and adiponectin levels of 96 T2DM patients and 85 healthy subjects were determined by ELISA, and their associations with adiposity, glucose and lipid profiles were studied. In a subgroup of this study, the 75-g oral glucose tolerance test (OGTT was performed in 20 healthy and 20 T2DM subjects to evaluate the relationship among serum levels of CTRP1 and adiponectin, insulin secretion and insulin sensitivity. RESULTS: Serum CTRP1 levels were significantly increased in patients with T2DM, compared with healthy controls (p<0.001. Similar to adiponectin, serum levels of CTRP1 were significantly correlated to several parameters involved in glucose metabolism and insulin resistance, and independently associated with fasting glucose levels (p<0.05 after BMI and gender adjustments. Furthermore, CTRP1 levels were positively correlated to insulin secretion, while negatively to insulin sensitivity, as measured by OGTT. CONCLUSION: CTRP1 is a novel adipokine associated with T2DM in humans. The paradoxical increase of serum CTRP1 levels in T2DM subjects may be due to a compensatory response to the adverse glucose and lipid metabolism, which warrants further investigation.

  15. Mechanisms of HIV entry into the CNS: increased sensitivity of HIV infected CD14+CD16+ monocytes to CCL2 and key roles of CCR2, JAM-A, and ALCAM in diapedesis.

    Science.gov (United States)

    Williams, Dionna W; Calderon, Tina M; Lopez, Lillie; Carvallo-Torres, Loreto; Gaskill, Peter J; Eugenin, Eliseo A; Morgello, Susan; Berman, Joan W

    2013-01-01

    As HIV infected individuals live longer, the prevalence of HIV associated neurocognitive disorders is increasing, despite successful antiretroviral therapy. CD14(+)CD16(+) monocytes are critical to the neuropathogenesis of HIV as they promote viral seeding of the brain and establish neuroinflammation. The mechanisms by which HIV infected and uninfected monocytes cross the blood brain barrier and enter the central nervous system are not fully understood. We determined that HIV infection of CD14(+)CD16(+) monocytes resulted in their highly increased transmigration across the blood brain barrier in response to CCL2 as compared to uninfected cells, which did not occur in the absence of the chemokine. This exuberant transmigration of HIV infected monocytes was due, at least in part, to increased CCR2 and significantly heightened sensitivity to CCL2. The entry of HIV infected and uninfected CD14(+)CD16(+) monocytes into the brain was facilitated by significantly increased surface JAM-A, ALCAM, CD99, and PECAM-1, as compared to CD14(+) cells that are CD16 negative. Upon HIV infection, there was an additional increase in surface JAM-A and ALCAM on CD14(+)CD16(+) monocytes isolated from some individuals. Antibodies to ALCAM and JAM-A inhibited the transmigration of both HIV infected and uninfected CD14(+)CD16(+) monocytes across the BBB, demonstrating their importance in facilitating monocyte transmigration and entry into the brain parenchyma. Targeting CCR2, JAM-A, and ALCAM present on CD14(+)CD16(+) monocytes that preferentially infiltrate the CNS represents a therapeutic strategy to reduce viral seeding of the brain as well as the ongoing neuroinflammation that occurs during HIV pathogenesis.

  16. Mechanisms of HIV entry into the CNS: increased sensitivity of HIV infected CD14+CD16+ monocytes to CCL2 and key roles of CCR2, JAM-A, and ALCAM in diapedesis.

    Directory of Open Access Journals (Sweden)

    Dionna W Williams

    Full Text Available As HIV infected individuals live longer, the prevalence of HIV associated neurocognitive disorders is increasing, despite successful antiretroviral therapy. CD14(+CD16(+ monocytes are critical to the neuropathogenesis of HIV as they promote viral seeding of the brain and establish neuroinflammation. The mechanisms by which HIV infected and uninfected monocytes cross the blood brain barrier and enter the central nervous system are not fully understood. We determined that HIV infection of CD14(+CD16(+ monocytes resulted in their highly increased transmigration across the blood brain barrier in response to CCL2 as compared to uninfected cells, which did not occur in the absence of the chemokine. This exuberant transmigration of HIV infected monocytes was due, at least in part, to increased CCR2 and significantly heightened sensitivity to CCL2. The entry of HIV infected and uninfected CD14(+CD16(+ monocytes into the brain was facilitated by significantly increased surface JAM-A, ALCAM, CD99, and PECAM-1, as compared to CD14(+ cells that are CD16 negative. Upon HIV infection, there was an additional increase in surface JAM-A and ALCAM on CD14(+CD16(+ monocytes isolated from some individuals. Antibodies to ALCAM and JAM-A inhibited the transmigration of both HIV infected and uninfected CD14(+CD16(+ monocytes across the BBB, demonstrating their importance in facilitating monocyte transmigration and entry into the brain parenchyma. Targeting CCR2, JAM-A, and ALCAM present on CD14(+CD16(+ monocytes that preferentially infiltrate the CNS represents a therapeutic strategy to reduce viral seeding of the brain as well as the ongoing neuroinflammation that occurs during HIV pathogenesis.

  17. Otters Increasing - Threats Increasing

    Directory of Open Access Journals (Sweden)

    Andreas Kranz

    1994-10-01

    Full Text Available In some parts of Central Europe populations of otters are apparently increasing. Until recently, no research was being conducted on the ecology of otters in mainly artificial habitats like fish farms. Otters are not only a new source of conflict requiring species management, but appear once again threatened by illegal hunting. Austria is dealing with this problem using compensation for otter damage, electric fencing and translocation of problem otters. Despite a rise in illegal killing, Austria does not formally recognise this as a threat.

  18. Thioredoxin reductase inhibitor ethaselen increases the drug sensitivity of the colon cancer cell line LoVo towards cisplatin via regulation of G1 phase and reversal of G2/M phase arrest.

    Science.gov (United States)

    Fu, Jia-Ning; Li, Jing; Tan, Qiang; Yin, Han-Wei; Xiong, Kun; Wang, Tian-Yu; Ren, Xiao-Yuan; Zeng, Hui-Hui

    2011-08-01

    We evaluated the combination treatment of ethaselen (BBSKE) as a thioredoxin reductase (TrxR) inhibitor plus cisplatin (CDDP) on the human colon adenocarcinoma cell line LoVo. Therapeutic effects ranging from nearly additive to clearly synergistic demonstrated an effective combination, i.e., the cytostatic dose of CDDP could be reduced without a loss in efficacy. To further investigate the cellular response mechanisms of these favorable outcomes, we analyzed the cell-cycle profiles, mRNA expression patterns, and protein levels of several key genes after incubation with BBSKE or CDDP separately and in combination. In appropriate conditions, CDDP induced arrest at the G2/M phase accompanied by the enhanced inhibitory phosphorylation of Cdk1 and the elevated protein expression of cyclin B1. BBSKE downregulated expression of cyclin D1 by increasing mRNA and protein levels of p21, and thus induced G1 phase arrest. BBSKE returned Cdk1 to an activated state, and reduced the protein level of cyclin B1 after incubation in combination with CDDP, which was consistent with the reduction in the percentage of cells in G2/M identified by flow cytometry. By regulating the G1 phase and reversing CDDP-induced G2/M phase arrest, BBSKE increases drug sensitivity of LoVo cells toward CDDP, and probably provides a meaningful anticancer strategy for further clinical studies.

  19. Selection of a MCF-7 Breast Cancer Cell Subpopulation with High Sensitivity to IL-1β: Characterization of and Correlation between Morphological and Molecular Changes Leading to Increased Invasiveness

    Directory of Open Access Journals (Sweden)

    Eloy Andres Pérez-Yépez

    2012-01-01

    Full Text Available Cancer and inflammation are closely related in tumor malignancy prognosis. Breast cancer MCF-7 cells have a poor invasive phenotype, although, under IL-1β stimulus, acquire invasive features. Cell response heterogeneity has precluded precise evaluation of the malignant transition. MCF-7A3 cells were selected for high sensitivity to IL-1β stimulus, uniform expression of CXCR4, and stability of IL1-RI. Structural changes, colony formation ability, proliferation rate, chemotaxis, Matrigel invasion, E-cadherin mRNA expression and protein localization were determined in these cells and in MCF-7 parental cells under the stimulus of IL-1β. Selected MCF-7A3 cells showed a uniform response to IL-1β stimulation increasing features of invasive cells such as scattering, colony formation, proliferation, chemokinesis and invasion. Basal expression of E-cadherin mRNA was higher, and IL-1β stimulus had no further effect at early times of cytokine exposure. Total E-cadherin levels remained unchanged in parental cells, whereas levels decreased, as MCF-7A3 cells became fibroblastoid or scattered. Triton X-100 soluble/insoluble E-cadherin ratios were highly increased in these cells, while, in MCF-7pl cells, ratios could not be correlated with morphology changes. MCF-7A3 cells uniform response to IL-1β allowed characterization of changes induced by the cytokine that had not been assessed when using heterogeneous cell lines.

  20. Genome-Wide Analysis of the AP2/ERF Gene Family in Physic Nut and Overexpression of the JcERF011 Gene in Rice Increased Its Sensitivity to Salinity Stress.

    Science.gov (United States)

    Tang, Yuehui; Qin, Shanshan; Guo, Yali; Chen, Yanbo; Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

    2016-01-01

    The AP2/ERF transcription factors play crucial roles in plant growth, development and responses to biotic and abiotic stresses. A total of 119 AP2/ERF genes (JcAP2/ERFs) have been identified in the physic nut genome; they include 16 AP2, 4 RAV, 1 Soloist, and 98 ERF genes. Phylogenetic analysis indicated that physic nut AP2 genes could be divided into 3 subgroups, while ERF genes could be classed into 11 groups or 43 subgroups. The AP2/ERF genes are non-randomly distributed across the 11 linkage groups of the physic nut genome and retain many duplicates which arose from ancient duplication events. The expression patterns of several JcAP2/ERF duplicates in the physic nut showed differences among four tissues (root, stem, leaf, and seed), and 38 JcAP2/ERF genes responded to at least one abiotic stressor (drought, salinity, phosphate starvation, and nitrogen starvation) in leaves and/or roots according to analysis of digital gene expression tag data. The expression of JcERF011 was downregulated by salinity stress in physic nut roots. Overexpression of the JcERF011 gene in rice plants increased its sensitivity to salinity stress. The increased expression levels of several salt tolerance-related genes were impaired in the JcERF011-overexpressing plants under salinity stress.

  1. Increased gut hormones and insulin sensitivity index following a 3-d intervention with a barley kernel-based product: a randomised cross-over study in healthy middle-aged subjects.

    Science.gov (United States)

    Nilsson, Anne C; Johansson-Boll, Elin V; Björck, Inger M E

    2015-09-28

    Certain purified indigestible carbohydrates such as inulin have been shown to stimulate gut-derived hormones involved in glycaemic regulation and appetite regulation, and to counteract systemic inflammation through a gut microbiota-mediated mechanism. Less is known about the properties of indigestible carbohydrates intrinsic to food. The aim of this study was to investigate the possibility to affect release of endogenous gut hormones and ameliorate appetite control and glycaemic control by ingestion of a whole-grain cereal food product rich in NSP and resistant starch in healthy humans. In all, twenty middle-aged subjects were provided with a barley kernel-based bread (BB) or a reference white wheat bread during 3 consecutive days, respectively, in a randomised cross-over design study. At a standardised breakfast the following day (day 4), blood was collected for the analysis of blood (b) glucose regulation, gastrointestinal hormones, markers of inflammation and markers of colonic fermentation; 3 d of intervention with BB increased gut hormones in plasma (p) the next morning at fasting (p-glucagon-like peptide-1; 56%) and postprandially (p-glucagon-like peptide-2; 13% and p-peptide YY; 18%). Breath H₂ excretion and fasting serum (s) SCFA concentrations were increased (363 and 18%, respectively), and b-glucose (22%) and s-insulin responses (17%) were decreased after BB intervention. Insulin sensitivity index (ISI(composite)) was also improved (25%) after BB. In conclusion, 3 d of intervention with BB increased systemic levels of gut hormones involved in appetite regulation, metabolic control and maintenance of gut barrier function, as well as improved markers of glucose homoeostasis in middle-aged subjects, altogether relevant for the prevention of obesity and the metabolic syndrome.

  2. Ursolic acid and rosiglitazone combination improves insulin sensitivity by increasing the skeletal muscle insulin-stimulated IRS-1 tyrosine phosphorylation in high-fat diet-fed C57BL/6J mice.

    Science.gov (United States)

    Sundaresan, Arjunan; Radhiga, Thangaiyan; Pugalendi, Kodukkur Viswanathan

    2016-06-01

    The aim of this present study was to investigate the effect of ursolic acid (UA) and rosiglitazone (RSG) on insulin sensitivity and proximal insulin signaling pathways in high-fat diet (HFD)-fed C57/BL/6J mice. Male C57BL/6J mice were fed either normal diet or HFD for 10 weeks, after which animals in each dietary group were divided into the following six groups (normal diet, normal diet plus UA and RSG, HFD alone, HFD plus UA, HFD plus RSG, and HFD plus UA and RSG) for the next 5 weeks. UA (5 mg/kg BW) and RSG (4 mg/kg BW) were administered as suspensions directly into the stomach using a gastric tube. The HFD diet elevated fasting plasma glucose, insulin, and homeostasis model assessment index. The expression of insulin receptor substrate (IRS)-1, phosphoinositide 3-kinase (PI3-kinase), Akt, and glucose transporter (GLUT) 4 were determined by Western blot analyses. The results demonstrated that combination treatment (UA/RSG) ameliorated HFD-induced glucose intolerance and insulin resistance by improving the homeostatic model assessment (HOMA) index. Further, combination treatment (UA/RSG) stimulated the IRS-1, PI3-kinase, Akt, and GLUT 4 translocation. These results strongly suggest that combination treatment (UA/RSG) activates IRS-PI3-kinase-Akt-dependent signaling pathways to induce GLUT 4 translocation and increases the expression of insulin receptor to improve glucose intolerance.

  3. Deletion of Metabotropic Glutamate Receptors 2 and 3 (mGlu2 & mGlu3 in Mice Disrupts Sleep and Wheel-Running Activity, and Increases the Sensitivity of the Circadian System to Light.

    Directory of Open Access Journals (Sweden)

    David Pritchett

    Full Text Available Sleep and/or circadian rhythm disruption (SCRD is seen in up to 80% of schizophrenia patients. The co-morbidity of schizophrenia and SCRD may in part stem from dysfunction in common brain mechanisms, which include the glutamate system, and in particular, the group II metabotropic glutamate receptors mGlu2 and mGlu3 (encoded by the genes Grm2 and Grm3. These receptors are relevant to the pathophysiology and potential treatment of schizophrenia, and have also been implicated in sleep and circadian function. In the present study, we characterised the sleep and circadian rhythms of Grm2/3 double knockout (Grm2/3-/- mice, to provide further evidence for the involvement of group II metabotropic glutamate receptors in the regulation of sleep and circadian rhythms. We report several novel findings. Firstly, Grm2/3-/- mice demonstrated a decrease in immobility-determined sleep time and an increase in immobility-determined sleep fragmentation. Secondly, Grm2/3-/- mice showed heightened sensitivity to the circadian effects of light, manifested as increased period lengthening in constant light, and greater phase delays in response to nocturnal light pulses. Greater light-induced phase delays were also exhibited by wildtype C57Bl/6J mice following administration of the mGlu2/3 negative allosteric modulator RO4432717. These results confirm the involvement of group II metabotropic glutamate receptors in photic entrainment and sleep regulation pathways. Finally, the diurnal wheel-running rhythms of Grm2/3-/- mice were perturbed under a standard light/dark cycle, but their diurnal rest-activity rhythms were unaltered in cages lacking running wheels, as determined with passive infrared motion detectors. Hence, when assessing the diurnal rest-activity rhythms of mice, the choice of assay can have a major bearing on the results obtained.

  4. Climate Sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Lindzen, Richard [M.I.T.

    2011-11-09

    Warming observed thus far is entirely consistent with low climate sensitivity. However, the result is ambiguous because the sources of climate change are numerous and poorly specified. Model predictions of substantial warming aredependent on positive feedbacks associated with upper level water vapor and clouds, but models are notably inadequate in dealing with clouds and the impacts of clouds and water vapor are intimately intertwined. Various approaches to measuring sensitivity based on the physics of the feedbacks will be described. The results thus far point to negative feedbacks. Problems with these approaches as well as problems with the concept of climate sensitivity will be described.

  5. Gluten Sensitivity

    Science.gov (United States)

    ... in other products like medicines, vitamins, and supplements. People with gluten sensitivity have problems with gluten. It is different from celiac disease, an immune disease in which people can't eat gluten because it will damage ...

  6. Path Sensitization

    Institute of Scientific and Technical Information of China (English)

    赵著行; 闵应骅; 等

    1997-01-01

    For different delay models,the concept of sensitization can be very different.Traditonal concepts of sensitization cannot precisely describe circuit behavior when the input vectors change very fast.Using Boolean process aporoach,this paper presents a new definition of sensitization for arbitrary input waveforms.By this new concept it is found that if the inputs of a combinational circuit can change at any time,and each gate's delay varies within an interval (bounded gate delay model),then every path,which is not necessarily a single topological path,is sensitizable.From the experimental results it can be seen that,all nonsensitizable paths for traditional concepts actually can propagate transitions along them for some input waveforms.However,specified time between input transitions(STBIT) and minimum permissible pulse width(ε)are two major factors to make some paths non-sensitizable.

  7. Non-conjugate potential-stepping phenothiazine and phenoxazine based polymer hole-transport material for dye-sensitized solar cells & increasing void space in porous titanium dioxide: To study diffusion properties of a cobalt mediator

    Science.gov (United States)

    Persson, Kristoffer

    As energy demands increase so has the search for alternative sources of energy. Although, fossil fuels have proven useful in energy production, they are also detrimental due to the negative impact on our environment. Considering the current alternative energy sources, such as wind, hydroelectric, biofuels, etc, one source of alternative energy shines above the rest, solar energy. Solar energy provides a possible solution to the energy demands of our modern world with little effect on the environment. The only waste produced from the solar cell industry is from producing and recycling the cells. After production, solar cells require no resources to function other than solar radiation, and no waste is produced. The sun has been powering life on this planet for billions of years, and bombards the earth with 3x1024 J of energy per year. Only 0.02% of this energy is currently needed to power the world, thus making the sun a viable solution to energy demands, while decreasing current pollution issues. This thesis focuses on dye sensitized solar cell (DSSCs), in particular, the Grätzel cell, which incorporates thin films of TiO2 as the semiconductor, DSSC's work very similarly to a battery, but instead of using chemical energy to drive electrons through the circuit, it uses photons. Several issues have arisen with these types of solar cells and their use in the modern world. One particular problem is that the iodide/triiodide (I -/I3-) mediator, which currently produces the most efficient DSSCs, is corrosive and volatile. To address this and other issues, a conductive phenothiazine (PTZ) and phenoxazine (POZ) based polymer is hypothesized to be a suitable replacement for the mediator and solvent by acting as a charge separator and hole transport material, without any volatile or corrosive problems. This polymer would hypothetically function similarly to proposed electron transport in DNA. When charges are injected into a DNA strand they are transferred through

  8. The prevalence of metabolic syndrome increases with serum high sensitivity C-reactive protein concentration in individuals without a history of cardiovascular disease: a report from a large Persian cohort.

    Science.gov (United States)

    Kazemi-Bajestani, Seyyed Mr; Tayefi, Maryam; Ebrahimi, Mahmoud; Heidari-Bakavoli, Ali R; Moohebati, Mohsen; Parizadeh, Seyyed Mr; Esmaeili, Habibollah; Ferns, Gordon Aa; Ghayour-Mobarhan, Majid

    2017-01-01

    Background Metabolic syndrome is defined by a clustering of cardiovascular risk factors and is associated with a heightened inflammatory state. A raised serum high-sensitivity C-reactive protein, a marker of inflammation, is also known to associate with cardiovascular risk. We have investigated the relationship between the presence of metabolic syndrome and serum high-sensitivity C-reactive protein concentration in a large representative Persian population cohort without a history of cardiovascular disease. Methods The MASHAD study population cohort comprised 9778 subjects, who were recruited from the city of Mashhad, Iran, between 2007 and 2008. Several cardiovascular risk factors were measured in this population without cardiovascular disease. Individuals were categorized into quartiles of serum high-sensitivity C-reactive protein concentration: first quartile - 0.72 (0.59-0.85) (median [range]) mg/L, second quartile - 1.30 (1.14-1.4) mg/L, third quartile - 2.29 (1.92-2.81) mg/L and fourth quartile - 6.63 (4.61-11.95) mg/L, respectively. The prevalence of metabolic syndrome in each quartile was determined using either International Diabetes Federation or Adult Treatment Panel III criteria. Results The prevalence of metabolic syndrome was highest in the fourth quartile for serum high-sensitivity C-reactive protein (1220 subjects [50.0%]), and significantly higher than that in the first quartile (reference group) (634 subjects [25.9%]) ( P history of cardiovascular disease in our Persian cohort.

  9. Sensitive innovation

    DEFF Research Database (Denmark)

    Søndergaard, Katia Dupret

    Present paper discusses sources of innovation as heterogenic and at times intangible processes. Arguing for heterogeneity and intangibility as sources of innovation originates from a theoretical reading in STS and ANT studies (e.g. Callon 1986, Latour 1996, Mol 2002, Pols 2005) and from field work...... in the area of mental health (Dupret Søndergaard 2009, 2010). The concept of sensitive innovation is developed to capture and conceptualise exactly those heterogenic and intangible processes. Sensitive innovation is therefore primarily a way to understand innovative sources that can be......, but are not necessarily, recognized and acknowledged as such in the outer organisational culture or by management. The added value that qualifies these processes to be defined as “innovative” are thus argued for along different lines than in more traditional innovation studies (e.g. studies that build on the classic...

  10. A non-radioactive DAPI-based high-throughput in vitro assay to assess Plasmodium falciparum responsiveness to antimalarials--increased sensitivity of P. falciparum to chloroquine in Senegal.

    Science.gov (United States)

    Ndiaye, Daouda; Patel, Vishal; Demas, Allison; LeRoux, Michele; Ndir, Omar; Mboup, Souleymane; Clardy, Jon; Lakshmanan, Viswanathan; Daily, Johanna P; Wirth, Dyann F

    2010-02-01

    The spread of Plasmodium falciparum drug resistance is outpacing new antimalarial development and compromising effective malaria treatment. Combination therapy is widely implemented to prolong the effectiveness of currently approved antimalarials. To maximize utility of available drugs, periodic monitoring of drug efficacy and gathering of accurate information regarding parasite-sensitivity changes are essential. We describe a high-throughput, non-radioactive, field-based assay to evaluate in vitro antimalarial drug sensitivity of P. falciparum isolates from 40 Senegalese patients. Compared with earlier years, we found a significant decrease in chloroquine in vitro and in genotypic resistances (> 50% and > 65%, respectively, in previous studies) with only 23% of isolates showing resistance. This is possibly caused by a withdrawal of chloroquine from Senegal in 2002. We also found a range of artemisinin responses. Prevalence of drug resistance is dynamic and varies by region. Therefore, the implementation of non-radioactive, robust, high-throughput antimalarial sensitivity assays is critical for defining region-specific prophylaxis and treatment guidelines.

  11. A Non-Radioactive DAPI-based High-Throughput In Vitro Assay to Assess Plasmodium falciparum Responsiveness to Antimalarials—Increased Sensitivity of P. falciparum to Chloroquine in Senegal

    Science.gov (United States)

    Ndiaye, Daouda; Patel, Vishal; Demas, Allison; LeRoux, Michele; Ndir, Omar; Mboup, Souleymane; Clardy, Jon; Lakshmanan, Viswanathan; Daily, Johanna P.; Wirth, Dyann F.

    2010-01-01

    The spread of Plasmodium falciparum drug resistance is outpacing new antimalarial development and compromising effective malaria treatment. Combination therapy is widely implemented to prolong the effectiveness of currently approved antimalarials. To maximize utility of available drugs, periodic monitoring of drug efficacy and gathering of accurate information regarding parasite-sensitivity changes are essential. We describe a high-throughput, non-radioactive, field-based assay to evaluate in vitro antimalarial drug sensitivity of P. falciparum isolates from 40 Senegalese patients. Compared with earlier years, we found a significant decrease in chloroquine in vitro and in genotypic resistances (> 50% and > 65%, respectively, in previous studies) with only 23% of isolates showing resistance. This is possibly caused by a withdrawal of chloroquine from Senegal in 2002. We also found a range of artemisinin responses. Prevalence of drug resistance is dynamic and varies by region. Therefore, the implementation of non-radioactive, robust, high-throughput antimalarial sensitivity assays is critical for defining region-specific prophylaxis and treatment guidelines. PMID:20133997

  12. Knock-out of SO1377 gene, which encodes the member of a conserved hypothetical bacterial protein family COG2268, results in alteration of iron metabolism, increased spontaneous mutation and hydrogen peroxide sensitivity in Shewanella oneidensis MR-1

    Directory of Open Access Journals (Sweden)

    Klingeman Dawn M

    2006-04-01

    Full Text Available Abstract Background Shewanella oneidensis MR-1 is a facultative, gram-negative bacterium capable of coupling the oxidation of organic carbon to a wide range of electron acceptors such as oxygen, nitrate and metals, and has potential for bioremediation of heavy metal contaminated sites. The complete 5-Mb genome of S. oneidensis MR-1 was sequenced and standard sequence-comparison methods revealed approximately 42% of the MR-1 genome encodes proteins of unknown function. Defining the functions of hypothetical proteins is a great challenge and may need a systems approach. In this study, by using integrated approaches including whole genomic microarray and proteomics, we examined knockout effects of the gene encoding SO1377 (gi24372955, a member of the conserved, hypothetical, bacterial protein family COG2268 (Clusters of Orthologous Group in bacterium Shewanella oneidensis MR-1, under various physiological conditions. Results Compared with the wild-type strain, growth assays showed that the deletion mutant had a decreased growth rate when cultured aerobically, but not affected under anaerobic conditions. Whole-genome expression (RNA and protein profiles revealed numerous gene and protein expression changes relative to the wild-type control, including some involved in iron metabolism, oxidative damage protection and respiratory electron transfer, e. g. complex IV of the respiration chain. Although total intracellular iron levels remained unchanged, whole-cell electron paramagnetic resonance (EPR demonstrated that the level of free iron in mutant cells was 3 times less than that of the wild-type strain. Siderophore excretion in the mutant also decreased in iron-depleted medium. The mutant was more sensitive to hydrogen peroxide and gave rise to 100 times more colonies resistant to gentamicin or kanamycin. Conclusion Our results showed that the knock-out of SO1377 gene had pleiotropic effects and suggested that SO1377 may play a role in iron

  13. Price increase

    CERN Multimedia

    2006-01-01

    Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced, as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

  14. Price increase

    CERN Multimedia

    2005-01-01

    Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

  15. Increased sensitivity of photosynthesis to antimycin A induced by inactivation of the chloroplast ndhB gene. Evidence for a participation of the NADH-dehydrogenase complex to cyclic electron flow around photosystem I.

    Science.gov (United States)

    Joët, T; Cournac, L; Horvath, E M; Medgyesy, P; Peltier, G

    2001-04-01

    Tobacco (Nicotiana tabacum var Petit Havana) ndhB-inactivated mutants (ndhB-) obtained by plastid transformation (E.M. Horvath, S.O. Peter, T. Joët, D. Rumeau, L. Cournac, G.V. Horvath, T.A. Kavanagh, C. Schäfer, G. Peltier, P. MedgyesyHorvath [2000] Plant Physiol 123: 1337-1350) were used to study the role of the NADH-dehydrogenase complex (NDH) during photosynthesis and particularly the involvement of this complex in cyclic electron flow around photosystem I (PSI). Photosynthetic activity was determined on leaf discs by measuring CO2 exchange and chlorophyll fluorescence quenchings during a dark-to-light transition. In the absence of treatment, both non-photochemical and photochemical fluorescence quenchings were similar in ndhB- and wild type (WT). When leaf discs were treated with 5 microM antimycin A, an inhibitor of cyclic electron flow around PSI, both quenchings were strongly affected. At steady state, maximum photosynthetic electron transport activity was inhibited by 20% in WT and by 50% in ndhB-. Under non-photorespiratory conditions (2% O2, 2,500 microL x L(-1) CO2), antimycin A had no effect on photosynthetic activity of WT, whereas a 30% inhibition was observed both on quantum yield of photosynthesis assayed by chlorophyll fluorescence and on CO2 assimilation in ndhB-. The effect of antimycin A on ndhB- could not be mimicked by myxothiazol, an inhibitor of the mitochondrial cytochrome bc1 complex, therefore showing that it is not related to an inhibition of the mitochondrial electron transport chain but rather to an inhibition of cyclic electron flow around PSI. We conclude to the existence of two different pathways of cyclic electron flow operating around PSI in higher plant chloroplasts. One of these pathways, sensitive to antimycin A, probably involves ferredoxin plastoquinone reductase, whereas the other involves the NDH complex. The absence of visible phenotype in ndhB- plants under normal conditions is explained by the complement of these two

  16. Study of dynamic sensitivity of rock slope under excitation function role of force increase mutation%力幅突变激扰作用的岩石边坡动力敏感性研究

    Institute of Scientific and Technical Information of China (English)

    王建国; 王振伟

    2013-01-01

    动载荷作用引起岩石边坡失稳破坏,尤其力幅突变激扰作用对边坡稳定影响很大.对动、静载荷作用下岩石力学性质进行了分析,建立了岩石边坡非线性运动方程,分析了岩石边坡动力变形模型及非线性动力响应,得出当扰动频率增加到一定程度,滑体振幅突然增加,产生向上突跳并随力幅的增加继续增加:反之,当力幅较大并逐渐减小时,滑体振幅也随之减小,当扰动的振幅减小至一定程度,滑体振幅突然降低,产生向下突跳减小.对初始条件和力幅突变激扰对岩石力学非线性振动系统的影响进行了分析,得到初始条件的微小变化可引起系统响应的巨大差异,当振幅A极小时,线性系统的振荡很弱,它对非线性系统的作用也很弱,整个系统的运动便可看作两运动的独立叠加.当振幅A再加大到使其幅值超过非线性系统三奇点之间的间隔时,系统可以在这些奇点之间来回跃迁振荡,从而运动复杂化,随振幅A的增加,系统从倍周期运动向混运动变化,研究结果可为岩石边坡的动力稳定提供指导.%The dynamic loading leads to instability and failure of rock slope.Especially,the role of force increase mutation has a great influence on slope stability.The rock mechanical properties are analyzed under static and dynamic loadings.And then,the nonlinear equation of rock slope is established.The dynamic deformation model of rock slope and the nonlinear dynamic response are studied.The amplitude of the sliding body suddenly increase,resulting in the sudden jump up and continue to increasing with the increase of the force,when the disturbance frequency to a certain extent.Conversely,the amplitude of the landslide suddenly reduces,resulting in the sudden decreases when the perturbation amplitude reduces to a certain extent.Tiny changes in initial conditions can cause a huge difference of the system response.The movement of the entire system can

  17. Nymphaea nouchali Burm. f. hydroalcoholic seed extract increases glucose consumption in 3T3-L1 adipocytes through activation of peroxisome proliferator-activated receptor gamma and insulin sensitization

    Directory of Open Access Journals (Sweden)

    Mabel Parimala

    2015-01-01

    Full Text Available Nymphaea nouchali Burm. f. (Family - Nymphaeaceae is a well-known medicinal plant used in the Indian ayurvedic system of medicine for treating diabetes. The seeds especially have been prescribed for diabetes. The hydroalcoholic extract of N. nouchali seeds has been demonstrated to possess anti-hyperglycemic effects in diabetic rats, but the functional mechanism remains unknown. The nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARγ is noted to play an important role in glucose and lipid homeostasis. This study was hence focused in evaluating the effect of the extract on PPARγ activation, adipocyte differentiation, and glucose consumption in 3T3-L1 cells. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT, followed by adipogenesis assay using Oil Red O technique. Glucose consumption of preadipocytes and adipocytes in the presence of the extract was also determined. Real-time polymerase chain reaction was performed to identify the expression of genes involved in glucose consumption in the adipocytes. MTT assay confirmed the extract to be nontoxic, and Oil Red O staining confirmed enhanced adipocyte differentiation of 3T3-L1 cells in a dose-dependent manner. The extract also increased the expression of PPARγ target gene, which in turn enhanced the expression of GLUT-4. The data, therefore, suggests that N. nouchali seed extract promotes adipocyte differentiation and glucose consumption by inducing PPARγ activation, which in turn increases mRNA GLUT-4 expression and subsequently enhances insulin-responsiveness in insulin target tissues.

  18. Nymphaea nouchali Burm. f. hydroalcoholic seed extract increases glucose consumption in 3T3-L1 adipocytes through activation of peroxisome proliferator-activated receptor gamma and insulin sensitization.

    Science.gov (United States)

    Parimala, Mabel; Debjani, M; Vasanthi, Hannah Rachel; Shoba, Francis Gricilda

    2015-01-01

    Nymphaea nouchali Burm. f. (Family - Nymphaeaceae) is a well-known medicinal plant used in the Indian ayurvedic system of medicine for treating diabetes. The seeds especially have been prescribed for diabetes. The hydroalcoholic extract of N. nouchali seeds has been demonstrated to possess anti-hyperglycemic effects in diabetic rats, but the functional mechanism remains unknown. The nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARγ) is noted to play an important role in glucose and lipid homeostasis. This study was hence focused in evaluating the effect of the extract on PPARγ activation, adipocyte differentiation, and glucose consumption in 3T3-L1 cells. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), followed by adipogenesis assay using Oil Red O technique. Glucose consumption of preadipocytes and adipocytes in the presence of the extract was also determined. Real-time polymerase chain reaction was performed to identify the expression of genes involved in glucose consumption in the adipocytes. MTT assay confirmed the extract to be nontoxic, and Oil Red O staining confirmed enhanced adipocyte differentiation of 3T3-L1 cells in a dose-dependent manner. The extract also increased the expression of PPARγ target gene, which in turn enhanced the expression of GLUT-4. The data, therefore, suggests that N. nouchali seed extract promotes adipocyte differentiation and glucose consumption by inducing PPARγ activation, which in turn increases mRNA GLUT-4 expression and subsequently enhances insulin-responsiveness in insulin target tissues.

  19. Epirubicin increases the sensitivity of gastric cancer BGC823 cells to TRAIL%表阿霉素提高胃癌BGC823细胞对TRAIL的敏感性

    Institute of Scientific and Technical Information of China (English)

    徐玲; 曲秀娟; 刘云鹏; 刘静; 罗颖; 张晔; 侯科佐

    2012-01-01

    目的:研究表阿霉素对TRAIL诱导胃癌细胞BGC823细胞凋亡的影响,探讨脂筏和死亡受体4(DR4)在TRAIL诱导细胞凋亡中的作用.方法:采用MTT法测定细胞活力,流式细胞仪检测细胞凋亡,免疫荧光显微技术检测脂筏和DR4在细胞膜的分布.结果:(0.1-50)μg/ml表阿霉素处理BGC823细胞24h,抑制细胞增殖50%的药物浓度(IC50)为(4.61±0.62)μg/ml.在BGC823细胞中,100ng/ml的TRAIL导致轻度的增殖抑制和细胞凋亡,TRAIL(100ng/ml)联合表阿霉素(4.61μg/ml)引起明显的增殖抑制和细胞凋亡(P<0.05).与对照组相比,100ng/ml的TRAIL作用BGC823细胞24 h,没有引起明显的脂筏聚集或DR4聚集.表阿霉素(4.61μg/ml)明显促进脂筏聚集和DR4聚集,同时观察到DR4和脂筏的共定位.表阿霉素和TRAIL联合作用24 h,同样观察到DR4定位在聚集的脂筏内.结论:表阿霉素通过促进DR4在脂筏聚集增强TRAIL诱导的胃癌BGC823细胞凋亡.%Objective: To assess the effect of epirubicin on TRAIL - induced apoptosis in gastric cancer BGC823 cells, and the action of lipid rafts and death receptor 4 ( DR4 ) in TRAIL - induced apoptosis. Methods: Cell proliferation was measured using MTT assay. Cell apoptosis was determined by flow cytometry. The distribution of lipid raft and DR4 in cell membranes was analyzed by immunofluorescence microscopy. Results: BGC823 cells were treated with ( 0. 1 -50 )μg/ ml epirubicin for 24 h, the concentration of 50% inhibition of cell proliferation ( IC50 ) was ( 4. 61 ± 0. 62 )μg/ml. Treatment with 100 ng/ml TRAIL for 24 h resulted in a slight reduction in cell viability and a little increase in cell apoptosis in BGC823 cells. Treatment with TRAIL ( 100ng/ml ) and epirubicin ( 4. 61μg/ml ) leaded to a significant reduction in cell viability and a dramatic increase in cell apoptosis ( P < 0. 05 ). 100ng/ml TRAIL did not induce obvious lipid raft aggregation or DR4 clustering. Epirubicin ( 4. 61 μg/ml ) significantly promoted

  20. Estratégias para aumentar a sensibilidade da farmacovigilância em Portugal Estrategias para aumentar la sensibilidad de la farmacovigilancia en Portugal Strategies to increase the sensitivity of pharmacovigilance in Portugal

    Directory of Open Access Journals (Sweden)

    Inês Ribeiro-Vaz

    2011-02-01

    reaction, the impact on public health and spontaneous reporting. With regard to relevance, adverse reactions were classified into severe and unexpected. Statistical analysis was performed, based on the intention-to-treat principle; generalized linear mixed models were applied, using the penalized quasi-likelihood method. The pharmacists studied were followed during a period of 20 months. RESULTS: The intervention increased the rate of spontaneous reporting of adverse reactions three times (RR = 3.22; 95% CI 1.33;7.80, when compared to the control group. The relevance of reporting rose, with an increase in severe adverse reactions by approximately four times (RR = 3.87; 95% CI 1.29;11.61 and in unexpected adverse reactions by five times (RR = 5.02; 95% CI 1.33;18.93, compared to the control group. CONCLUSIONS: During a period of up to four months, educational interventions significantly increased the number and relevance of spontaneous reporting of adverse drug reactions by pharmacists in Northern Portugal.

  1. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S.

    2013-02-26

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  2. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A; Thompson, Vicki S

    2013-02-26

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  3. Increasing the sensitivity of the Jaffe reaction for creatinine

    Science.gov (United States)

    Tom, H. Y.

    1973-01-01

    Study of analytical procedure has revealed that linearity of creatinine calibration curve can be extended by using 0.03 molar picric acid solution made up in 70 percent ethanol instead of water. Three to five times more creatinine concentration can be encompassed within linear portion of calibration curve.

  4. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S.

    2017-03-28

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  5. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S

    2010-04-13

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  6. Increased Sensitivity to Possible Muonium to Antimuonium Conversion

    CERN Document Server

    Meyer, V; Jungmann, Klaus; Merkel, J; zu Putlitz, Gisbert; Reinhard, I; Träger, K; Schmidt, P V; Willmann, L; Engfer, R; Wirtz, H P; Abela, R; Bertl, W; Renker, D; Walter, H K; Karpukhin, V V; Kisel, I V; Korenchenko, A S; Korenchenko, S M; Kravchuk, N; Kuchinskii, N A; Moiseenko, A; Bagaturia, Yu S; Mzhavia, D A; Sakhelashvili, T M; Hughes, V W

    1998-01-01

    A new experimental search for muonium-antimuonium conversion was conducted at the Paul Scherrer Institute, Villigen, Switzerland. The preliminary analysis yielded one event fulfilling all required criteria at an expected background of 1.7(2) events due to accidental coincidences. An upper limit for the conversion probability in 0.1 T magnetic field is extracted as $8 \\cdot 10^{-11}$ (90% CL).

  7. A case of atrial tachycardia sensitive to increased caffeine intake.

    Science.gov (United States)

    Kinugawa, Toru; Kurita, Takashi; Nohara, Ryuji; Smith, Michael L

    2011-01-01

    A 33-year-old Japanese man with atrial tachycardia visited our clinic. He regularly consumed daily alcohol with cola, one cup of regular coffee, and a candy containing 0.7 mg of caffeine per tablet. After stopping his caffeine intake, his arrhythmia ameliorated. Since caffeine might be associated with his arrhythmia, a caffeine load test (equivalent to his daily intake of caffeine) was performed for 4 days. Atrial tachycardia time from a Holter recording was 44.2 minute/day before the caffeine load, compared with 215.2 minute/day during the caffeine load. Plasma caffeine concentration before and during caffeine loading was 3.1 mg/dL and 5.4 mg/dL, respectively. Caffeine use seemed to be an important factor for his atrial tachycardia, since his arrhythmia became worse during caffeine load testing and was ameliorated after the cessation of caffeine.

  8. Anxiety and Error Monitoring: Increased Error Sensitivity or Altered Expectations?

    Science.gov (United States)

    Compton, Rebecca J.; Carp, Joshua; Chaddock, Laura; Fineman, Stephanie L.; Quandt, Lorna C.; Ratliff, Jeffrey B.

    2007-01-01

    This study tested the prediction that the error-related negativity (ERN), a physiological measure of error monitoring, would be enhanced in anxious individuals, particularly in conditions with threatening cues. Participants made gender judgments about faces whose expressions were either happy, angry, or neutral. Replicating prior studies, midline…

  9. Climate sensitivity in the Anthropocene

    Directory of Open Access Journals (Sweden)

    M. Previdi

    2011-09-01

    Full Text Available Understanding the sensitivity of Earth's climate to an imposed external forcing is one of the great challenges in science and a critical component of efforts to avoid dangerous anthropogenic interference with the climate system. Climate sensitivity (or equilibrium global surface warming to a doubling of atmospheric CO2 has long been estimated to be about 3 °C, considering only fast climate feedbacks associated with increases in water vapor, decreases in sea ice, and changes in clouds. However, evidence from Earth's history suggests that slower surface albedo feedbacks due to vegetation change and melting of Greenland and Antarctica can come into play on the timescales of interest to humans, which could increase the sensitivity to significantly higher values, as much as 6 °C. Even higher sensitivity may result as present-day land and ocean carbon sinks begin to lose their ability to sequester anthropogenic CO2 in the coming decades. The evolving view of climate sensitivity in the Anthropocene is therefore one in which a wider array of Earth system feedbacks are recognized as important. Since these feedbacks are overwhelmingly positive, the sensitivity is likely to be higher than has traditionally been assumed.

  10. Nonceliac gluten sensitivity.

    Science.gov (United States)

    Fasano, Alessio; Sapone, Anna; Zevallos, Victor; Schuppan, Detlef

    2015-05-01

    During the past decade there has been an impressive increase in popularity of the gluten-free diet (GFD)-now the most trendy alimentary habit in the United States and other countries. According to recent surveys, as many as 100 million Americans will consume gluten-free products within a year. Operating under the concept that the GFD benefits only individuals with celiac disease, health care professionals have struggled to separate the wheat from the chaff; there are claims that eliminating gluten from the diet increases health and helps with weight loss, or even that gluten can be harmful to every human being. However, apart from unfounded trends, a disorder related to ingestion of gluten or gluten-containing cereals, namely nonceliac gluten sensitivity (NCGS), has resurfaced in the literature, fueling a debate on the appropriateness of the GFD for people without celiac disease. Although there is clearly a fad component to the popularity of the GFD, there is also undisputable and increasing evidence for NCGS. However, we require a better understanding of the clinical presentation of NCGS, as well as its pathogenesis, epidemiology, management, and role in conditions such as irritable bowel syndrome, chronic fatigue, and autoimmunity. Before we can begin to identify and manage NCGS, there must be agreement on the nomenclature and definition of the disorder based on proper peer-reviewed scientific information. We review the most recent findings on NCGS and outline directions to dissipate some of the confusion related to this disorder.

  11. Tooth sensitivity and whitening.

    Science.gov (United States)

    Swift, Edward J

    2005-09-01

    This article presents a review of the basic concepts of tooth sensitivity and how those concepts apply to cervical dentin hypersensitivity and the sensitivity frequently associated with tooth whitening. The etiology and treatment of cervical dentin hypersensitivity are described. The clinical presentation, incidence, and predisposing factors for sensitivity associated with tooth whitening also are discussed.

  12. How sensitizing is chlorocresol?

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner; Hamann, K

    1984-01-01

    Chlorocresol is a biocide with widespread use in industry and pharmaceutical products. It is an occasional human contact sensitizer. The sensitizing potential of chlorocresol was judged strong using the guinea pig maximization test (GPMT) and doubtful in the less sensitive open epicutaneous test ...

  13. Drought sensitivity predicts habitat size sensitivity in an aquatic ecosystem.

    Science.gov (United States)

    Amundrud, Sarah L; Srivastava, Diane S

    2015-07-01

    Species and trophic richness often increase with habitat size. Although many ecological processes have been evoked to explain both patterns, the environmental stress associated with small habitats has rarely been considered. We propose that larger habitats may be species rich simply because their environmental conditions are within the fundamental niche of more species; larger habitats may also have more trophic levels if traits of predators render them vulnerable to environmental stress. We test this hypothesis using the aquatic insect larvae in water-filled bromeliads. In bromeliads, the probability of desiccation is greatest in small plants. For the 10 most common bromeliad insect taxa, we ask whether differences in drought tolerance and regional abundances between taxa predict community and trophic composition over a gradient of bromeliad size. First, we used bromeliad survey data to calculate the mean habitat size of occurrence of each taxon. Comparing the observed mean habitat size of occurrence to that expected from random species assembly based on differences in their regional abundances allowed us to obtain habitat size sensitivity indices (as Z scores) for the various insect taxa. Second, we obtained drought sensitivity indices by subjecting individual insects to drought and measuring the effects on relative growth rates in a mesocosm experiment. We found that drought sensitivity strongly, predicts habitat size sensitivity in bromeliad insects. However, an increase in trophic richness with habitat size could not be explained by an increased sensitivity of predators to drought, but rather by sampling effects, as predators were rare compared to lower trophic levels. This finding suggests that physiological tolerance to environmental stress can be relevant in explaining the universal increase in species with habitat size.

  14. Baroreceptor sensitivity and diabetes mellitus.

    Science.gov (United States)

    Rowaiye, Olumide Olatubosun; Jankowska, Ewa Anita; Ponikowska, Beata

    2013-01-01

    Diabetes mellitus (DM) is a disease of increasing incidence and prevalence. Arterial baroreceptors are stretch-sensitive receptors, which in a reflex manner are involved in the homeostatic control of arterial blood pressure. Diabetic subjects have depressed baroreflex sensitivity (BRS), although the exact pathomechanisms are unclear. In this review, we discuss the features, clinicaland prognostic implications of reduced BRS for diabetic patients and the potential involvement of cardiovascular autonomic neuropathy and atherosclerosis. Finally, we demonstrate evidence on interventions (e.g. pioglitazone, alpha-lipoic acid, leptin, fluvastatin, physicaltraining etc.) which could improve BRS and ameliorate cardiovascular autonomic dysfunction in diabetic patients.

  15. Culture-sensitive psychotraumatology

    Science.gov (United States)

    Schnyder, Ulrich; Bryant, Richard A.; Ehlers, Anke; Foa, Edna B.; Hasan, Aram; Mwiti, Gladys; Kristensen, Christian H.; Neuner, Frank; Oe, Misari; Yule, William

    2016-01-01

    Background Although there is some evidence of the posttraumatic stress disorder (PTSD) construct's cross cultural validity, trauma-related disorders may vary across cultures, and the same may be true for treatments that address such conditions. Experienced therapists tailor psychotherapy to each patient's particular situation, to the nature of the patient's psychopathology, to the stage of therapy, and so on. In addition, culture-sensitive psychotherapists try to understand how culture enhances the meaning of their patient's life history, the cultural components of their illness and help-seeking behaviors, as well as their expectations with regard to treatment. We cannot take for granted that all treatment-seeking trauma survivors speak our language or share our cultural values. Therefore, we need to increase our cultural competencies. Methods The authors of this article are clinicians and/or researchers from across the globe, working with trauma survivors in various settings. Each author focused on one or more specific cultural aspects of working with trauma survivors and highlighted the following aspects. Results As a result of culture-specific individual and collective meanings linked to trauma and trauma-related disorders survivors may be exposed to (self-)stigma in the aftermath of trauma. Patients who are reluctant to talk about their traumatic experiences may instead be willing to write or use other ways of accessing the painful memories such as drawing. In other cultures, community and family cohesion are crucial elements of recovery. While awareness of culture-specific aspects is important, we also need to beware of premature cultural stereotyping. When disseminating empirically supported psychotherapies for PTSD across cultures, a number of additional challenges need to be taken into account: many low and middle income countries have very limited resources available and suffer from a poor health infrastructure. Conclusions In summary, culture-sensitive

  16. Culture-sensitive psychotraumatology

    Directory of Open Access Journals (Sweden)

    Ulrich Schnyder

    2016-07-01

    Full Text Available Background: Although there is some evidence of the posttraumatic stress disorder (PTSD construct's cross cultural validity, trauma-related disorders may vary across cultures, and the same may be true for treatments that address such conditions. Experienced therapists tailor psychotherapy to each patient's particular situation, to the nature of the patient's psychopathology, to the stage of therapy, and so on. In addition, culture-sensitive psychotherapists try to understand how culture enhances the meaning of their patient's life history, the cultural components of their illness and help-seeking behaviors, as well as their expectations with regard to treatment. We cannot take for granted that all treatment-seeking trauma survivors speak our language or share our cultural values. Therefore, we need to increase our cultural competencies. Methods: The authors of this article are clinicians and/or researchers from across the globe, working with trauma survivors in various settings. Each author focused on one or more specific cultural aspects of working with trauma survivors and highlighted the following aspects. Results: As a result of culture-specific individual and collective meanings linked to trauma and trauma-related disorders survivors may be exposed to (self-stigma in the aftermath of trauma. Patients who are reluctant to talk about their traumatic experiences may instead be willing to write or use other ways of accessing the painful memories such as drawing. In other cultures, community and family cohesion are crucial elements of recovery. While awareness of culture-specific aspects is important, we also need to beware of premature cultural stereotyping. When disseminating empirically supported psychotherapies for PTSD across cultures, a number of additional challenges need to be taken into account: many low and middle income countries have very limited resources available and suffer from a poor health infrastructure. Conclusions: In summary

  17. Sensitivity and uncertainty analysis

    CERN Document Server

    Cacuci, Dan G; Navon, Ionel Michael

    2005-01-01

    As computer-assisted modeling and analysis of physical processes have continued to grow and diversify, sensitivity and uncertainty analyses have become indispensable scientific tools. Sensitivity and Uncertainty Analysis. Volume I: Theory focused on the mathematical underpinnings of two important methods for such analyses: the Adjoint Sensitivity Analysis Procedure and the Global Adjoint Sensitivity Analysis Procedure. This volume concentrates on the practical aspects of performing these analyses for large-scale systems. The applications addressed include two-phase flow problems, a radiative c

  18. Climate Sensitivity in the Anthropocene

    Science.gov (United States)

    Previdi, M.; Liepert, B. G.; Peteet, Dorothy M.; Hansen, J.; Beerling, D. J.; Broccoli, A. J.; Frolking, S.; Galloway, J. N.; Heimann, M.; LeQuere, C.; Levitus, S.; Ramaswamy, V.

    2014-01-01

    Climate sensitivity in its most basic form is defined as the equilibrium change in global surface temperature that occurs in response to a climate forcing, or externally imposed perturbation of the planetary energy balance. Within this general definition, several specific forms of climate sensitivity exist that differ in terms of the types of climate feedbacks they include. Based on evidence from Earth's history, we suggest here that the relevant form of climate sensitivity in the Anthropocene (e.g. from which to base future greenhouse gas (GHG) stabilization targets) is the Earth system sensitivity including fast feedbacks from changes in water vapour, natural aerosols, clouds and sea ice, slower surface albedo feedbacks from changes in continental ice sheets and vegetation, and climate-GHG feedbacks from changes in natural (land and ocean) carbon sinks. Traditionally, only fast feedbacks have been considered (with the other feedbacks either ignored or treated as forcing), which has led to estimates of the climate sensitivity for doubled CO2 concentrations of about 3 C. The 2×CO2 Earth system sensitivity is higher than this, being approx. 4-6 C if the ice sheet/vegetation albedo feedback is included in addition to the fast feedbacks, and higher still if climate-GHG feedbacks are also included. The inclusion of climate-GHG feedbacks due to changes in the natural carbon sinks has the advantage of more directly linking anthropogenic GHG emissions with the ensuing global temperature increase, thus providing a truer indication of the climate sensitivity to human perturbations. The Earth system climate sensitivity is difficult to quantify due to the lack of palaeo-analogues for the present-day anthropogenic forcing, and the fact that ice sheet and climate-GHG feedbacks have yet to become globally significant in the Anthropocene. Furthermore, current models are unable to adequately simulate the physics of ice sheet decay and certain aspects of the natural carbon and

  19. Glial involvement in trigeminal central sensitization

    Institute of Scientific and Technical Information of China (English)

    Yu-feng XIE

    2008-01-01

    Recent studies have indicated that trigeminal neurons exhibit central sensitization, an increase in the excitability of neurons within the central nervous system to the extent that a normally innocuous stimulus begins to produce pain after inflamma-tion or injury, and that glial activities play a vital role in this central sensitization. The involvement of glial cells in trigeminal central sensitization contains multiple mechanisms, including interaction with glutamatergic and purinergic receptors. A better understanding of the trigeminal central sensitization mediated by glial cells will help to find potential therapeutic targets and lead to developing new analge-sics for orofacial-specific pain with higher efficiency and fewer side-effects.

  20. Structure sensitivity in adsorption

    DEFF Research Database (Denmark)

    Hammer, Bjørk; Nielsen, Ole Holm; Nørskov, Jens Kehlet

    1997-01-01

    The structure sensitivity of CO adsorption on different flat, stepped, kinked and reconstructed Pt surfaces is studied using large-scale density-functional calculations. We find an extremely strong structure sensitivity in the adsorption energy with variations up to 1 eV (or 100%) from one...

  1. Mixed sensitivity design

    NARCIS (Netherlands)

    Kwakernaak, Huibert; Camacho, E.F.; Basanez, L.; Puente, de la J.A.

    2002-01-01

    Mixed sensitivity design of a linear multivariable control system amounts toshaping its sensitivity functions to achieve the design targets of closed-loop system performance and robustness. Both H∞ and H2 optimization may be used to this end. Various tools are available, in particular low and high f

  2. Multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Tran, Marie Thi Dao; Arendt-Nielsen, Lars; Kupers, Ron;

    2013-01-01

    BACKGROUND: Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by recurrent, non-specific symptoms in response to chemically unrelated exposures in non-toxic concentrations. Although the pathophysiology of MCS remains unknown, central sensitization may be an important factor...

  3. Tuned cavity magnetometer sensitivity.

    Energy Technology Data Exchange (ETDEWEB)

    Okandan, Murat; Schwindt, Peter

    2009-09-01

    We have developed a high sensitivity (sensitivity levels.

  4. Pulsed electric field increases reproduction.

    Science.gov (United States)

    Panagopoulos, Dimitris J

    2016-01-01

    Purpose To study the effect of pulsed electric field - applied in corona discharge photography - on Drosophila melanogaster reproduction, possible induction of DNA fragmentation, and morphological alterations in the gonads. Materials and methods Animals were exposed to different field intensities (100, 200, 300, and 400 kV/m) during the first 2-5 days of their adult lives, and the effect on reproductive capacity was assessed. DNA fragmentation during early- and mid-oogenesis was investigated by application of the TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) assay. Sections of follicles after fixation and embedding in resins were observed for possible morphological/developmental abnormalities. Results The field increased reproduction by up to 30% by increasing reproductive capacity in both sexes. The effect increased with increasing field intensities. The rate of increase diminished at the strongest intensities. Slight induction of DNA fragmentation was observed exclusively in the nurse (predominantly) and follicle cells, and exclusively at the two most sensitive developmental stages, i.e., germarium and predominantly stage 7-8. Sections of follicles from exposed females at stages of early and mid-oogennesis other than germarium and stages 7-8 did not reveal abnormalities. Conclusions (1) The specific type of electric field may represent a mild stress factor, inducing DNA fragmentation and cell death in a small percentage of gametes, triggering the reaction of the animal's reproductive system to increase the rate of gametogenesis in order to compensate the loss of a small number of gametes. (2) The nurse cells are the most sensitive from all three types of egg chamber cells. (3) The mid-oogenesis checkpoint (stage 7-8) is more sensitive to this field than the early oogenesis one (germarium) in contrast to microwave exposure. (4) Possible therapeutic applications, or applications in increasing fertility, should be investigated.

  5. The sensitivity in Electrical Impedance Tomography

    Directory of Open Access Journals (Sweden)

    A. I. Rybin

    2013-12-01

    Full Text Available Introduction. The concept of sensitivity in Electrical Impedance Tomography is introduced (first – fourth type. The experimental researches measuring the voltages on the phantom outline are conducted on the created layout (for uniform cylindrical vessel with brine and placed inhomogeneities in a vessel. The main part. The inverse problems are solved for simulated on PC phantom (the third type sensitivity and from measured results (the fourth type sensitivity by conductivity zones method using regularization by A. Tykhonov. The sensitivity to conductivity increasing of elements inside the phantom is significantly less than the sensitivity to resistance increasing. The results of measured voltages processing and the results of projection reconstruction (obtained from mathematical model and from measured results are described. Conclusions. The satisfactory agreements of reconstruction results between themselves and with mathematical and measured phantoms are shown.

  6. Contextual sensitivity in scientific reproducibility.

    Science.gov (United States)

    Van Bavel, Jay J; Mende-Siedlecki, Peter; Brady, William J; Reinero, Diego A

    2016-06-07

    In recent years, scientists have paid increasing attention to reproducibility. For example, the Reproducibility Project, a large-scale replication attempt of 100 studies published in top psychology journals found that only 39% could be unambiguously reproduced. There is a growing consensus among scientists that the lack of reproducibility in psychology and other fields stems from various methodological factors, including low statistical power, researcher's degrees of freedom, and an emphasis on publishing surprising positive results. However, there is a contentious debate about the extent to which failures to reproduce certain results might also reflect contextual differences (often termed "hidden moderators") between the original research and the replication attempt. Although psychologists have found extensive evidence that contextual factors alter behavior, some have argued that context is unlikely to influence the results of direct replications precisely because these studies use the same methods as those used in the original research. To help resolve this debate, we recoded the 100 original studies from the Reproducibility Project on the extent to which the research topic of each study was contextually sensitive. Results suggested that the contextual sensitivity of the research topic was associated with replication success, even after statistically adjusting for several methodological characteristics (e.g., statistical power, effect size). The association between contextual sensitivity and replication success did not differ across psychological subdisciplines. These results suggest that researchers, replicators, and consumers should be mindful of contextual factors that might influence a psychological process. We offer several guidelines for dealing with contextual sensitivity in reproducibility.

  7. Allergic sensitization: screening methods

    DEFF Research Database (Denmark)

    Ladics, Gregory S.; Fry, Jeremy; Goodman, Richard

    2014-01-01

    conformational epitopes, and protein families that become allergens. Some common challenges for predicting protein sensitization are addressed: (a) exposure routes; (b) frequency and dose of exposure; (c) dose-response relationships; (d) role of digestion, food processing, and the food matrix; (e) role...... of infection; (f) role of the gut microbiota; (g) influence of the structure and physicochemical properties of the protein; and (h) the genetic background and physiology of consumers. The consensus view is that sensitization screening models are not yet validated to definitively predict the de novo sensitizing...

  8. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel;

    2014-01-01

    was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...

  9. Spontaneous baroreflex sensitivity

    DEFF Research Database (Denmark)

    Barthel, Petra; Bauer, Axel; Müller, Alexander;

    2012-01-01

    Low baroreflex sensitivity (BRS) indicates poor prognosis after acute myocardial infarction. Noninvasive BRS assessment is complicated by nonstationarities and noise in electrocardiogram and pressure signals. Phase-rectified signal averaging is a novel signal processing technology overcoming...

  10. Charge-sensitive amplifier

    Directory of Open Access Journals (Sweden)

    Startsev V. I.

    2008-02-01

    Full Text Available The authors consider design and circuit design techniques of reduction of the influence of the pyroelectric effect on operation of the charge sensitive amplifiers. The presented experimental results confirm the validity of the measures taken to reduce the impact of pyroelectric currents. Pyroelectric currents are caused by the influence of the temperature gradient on the piezoelectric sensor and on the output voltage of charge sensitive amplifiers.

  11. Cobalt sensitization and dermatitis

    DEFF Research Database (Denmark)

    Thyssen, Jacob P

    2012-01-01

    : This clinical review article presents clinical and scientific data on cobalt sensitization and dermatitis. It is concluded that cobalt despite being a strong sensitizer and a prevalent contact allergen to come up on patch testing should be regarded as a very complex metal to test with. Exposure...... data together with clinical data from metal workers heavily exposed to cobalt suggest that patch-test reactions are sometimes false positive and that patch testers should carefully evaluate their clinical relevance....

  12. Tropical convection and climate sensitivity

    Science.gov (United States)

    Williams, Ian Nobuo

    Surface temperature has become a popular measure of climate change, but it does not provide the most critical test of climate models. This thesis presents new methods to evaluate climate models based on processes determining the climate sensitivity to radiative forcing from atmospheric greenhouse gases. Cloud radiative feedbacks depend on temperature and relative humidity profiles in addition to surface temperature, through the dependence of cloud type on boundary layer buoyancy. Buoyancy provides a reference to which the onset of deep convection is invariant, and gives a compact description of sea surface temperature changes and cloud feedbacks suitable for diagnostics and as a basis for simplified climate models. This thesis also addresses uncertainties in climate sensitivity involving terrestrial ecosystem responses to global warming. Different diagnostics support different conclusions about atmospheric transport model errors that could imply either stronger or weaker northern terrestrial carbon sinks. Equilibrium boundary layer concepts were previously used in idealized tropical climate models, and are extended here to develop a diagnostic of boundary layer trace gas transport and mixing. Hypotheses linking surface temperature to climate and precipitation sensitivity were tested in this thesis using comprehensive and idealized climate model simulations, and observational datasets. The results do not support the thermostat hypothesis that predicts deep cloud cover will increase with radiative forcing and limit sea surface temperatures to the maximum present-day warm pool temperature. Warm pool temperatures increased along with or even faster than the tropical average over the past several decades, while diagnosed deep cloud cover has not significantly increased, in agreement with global warming simulations. Precipitation sensitivity also depends on more than surface temperature alone, including thermodynamic profiles and air-sea temperature differences. The

  13. Habituation, sensitization and Pavlovian conditioning

    Directory of Open Access Journals (Sweden)

    Münire Özlem Çevik

    2014-02-01

    Full Text Available In this brief review, I argue that the impact of a stimulus on behavioral control increase as the distance of the stimulus to the body decreases. Habituation, i.e., decrement in response intensity repetition of the triggering stimulus, is the default state for sensory processing, and the likelihood of habituation is higher for distal stimuli. Sensitization, i.e., increment in response intensity upon stimulus repetition, occurs in a state dependent manner for proximal stimuli that make direct contact with the body. In Pavlovian conditioning paradigms, the US is always a more proximal stimulus than the CS. The mechanisms of associative and non-associative learning are not independent. CS-US pairings lead to formation of associations if sensitizing modulation from a proximal US prevents the habituation for a distal anticipatory CS.

  14. 沉默热休克蛋白27基因增强大肠癌细胞对5-FU化疗敏感性%Silencing gene of heat shock protein 27 increases the sensitivity to 5-FU in colorectal cancer cells

    Institute of Scientific and Technical Information of China (English)

    黄崇杰; 刘长宝; 郑晨果; 蔡锚

    2015-01-01

    2000. The transfection efifciency was observed by laser confocal mi-croscope. The expression of HSP27 was tested with qRT-PCR and Western blot analysis. Different concentrations of 5-FU were added to the cells, which were transfected with siRNA-HSP27 48 h before. Then, the inhibition rate was determined by CCK-8 after 24 h. Results:The correlation between the level of HSP27 expression and IC50 were positive. Real-time PCR and Western blot revealed that two targeted HSP27-siRNA could effectively inhibit the mRNA and protein expression of HSP27. CCK-8 showed that the transfection of HSP27-siRNA can improve the sensitivity of SW480 to 5-FU and the IC50 was downregulated signiifcantly. Conclusion:The corre-lation between the level of HSP27 expression of colon cancer cells and IC50 of 5-FU are positive. HSP27-siRNA leads to the efifcient inhibition of HSP27 expression in SW480 cells, and increase the sensitization to 5-FU.

  15. Sensitivity of resonant tunneling diode photodetectors

    Science.gov (United States)

    Pfenning, Andreas; Hartmann, Fabian; Langer, Fabian; Kamp, Martin; Höfling, Sven; Worschech, Lukas

    2016-09-01

    We have studied the sensitivity of AlGaAs/GaAs double barrier resonant tunneling diode photodetectors with an integrated GaInNAs absorption layer for light sensing at the telecommunication wavelength of λ = 1.3 μm for illumination powers from pico- to microwatts. The sensitivity decreases nonlinearly with power. An illumination power increase of seven orders of magnitude leads to a reduction of the photocurrent sensitivity from S I = 5.82 × 103 A W-1 to 3.2 A W-1. We attribute the nonlinear sensitivity-power dependence to an altered local electrostatic potential due to hole-accumulation that on the one hand tunes the tunneling current, but on the other hand affects the lifetime of photogenerated holes. In particular, the lifetime decreases exponentially with increasing hole population. The lifetime reduction results from an enhanced electrical field, a rise of the quasi-Fermi level, and an increased energy splitting within the triangular potential well. The non-constant sensitivity is a direct result of the non-constant lifetime. Based on these findings, we provide an expression that allows us to calculate the sensitivity as a function of illumination power and bias voltage, show a way to model the time-resolved photocurrent, and determine the critical power up to which the resonant tunneling diode photodetector sensitivity can be assumed constant.

  16. Sensitizing properties of proteins

    DEFF Research Database (Denmark)

    Poulsen, Lars K.; Ladics, Gregory S; McClain, Scott;

    2014-01-01

    The scope of allergy risk is diverse considering the myriad ways in which protein allergenicity is affected by physiochemical characteristics of proteins. The complexity created by the matrices of foods and the variability of the human immune system add additional challenges to understanding...... the relationship between sensitization potential and allergy disease. To address these and other issues, an April 2012 international symposium was held in Prague, Czech Republic, to review and discuss the state-of-the-science of sensitizing properties of protein allergens. The symposium, organized by the Protein...... Allergenicity Technical Committee of the International Life Sciences Institute's Health and Environmental Sciences Institute, featured presentations on current methods, test systems, research trends, and unanswered questions in the field of protein sensitization. A diverse group of over 70 interdisciplinary...

  17. Sensitivity of Complex Networks

    CERN Document Server

    Angulo, Marco Tulio; Liu, Yang-Yu; Barabási, Albert-László

    2016-01-01

    The sensitivity (i.e. dynamic response) of complex networked systems has not been well understood, making difficult to predict whether new macroscopic dynamic behavior will emerge even if we know exactly how individual nodes behave and how they are coupled. Here we build a framework to quantify the sensitivity of complex networked system of coupled dynamic units. We characterize necessary and sufficient conditions for the emergence of new macroscopic dynamic behavior in the thermodynamic limit. We prove that these conditions are satisfied only for architectures with power-law degree distributions. Surprisingly, we find that highly connected nodes (i.e. hubs) only dominate the sensitivity of the network up to certain critical frequency.

  18. Sensitivity analysis of SPURR

    Energy Technology Data Exchange (ETDEWEB)

    Witholder, R.E.

    1980-04-01

    The Solar Energy Research Institute has conducted a limited sensitivity analysis on a System for Projecting the Utilization of Renewable Resources (SPURR). The study utilized the Domestic Policy Review scenario for SPURR agricultural and industrial process heat and utility market sectors. This sensitivity analysis determines whether variations in solar system capital cost, operation and maintenance cost, and fuel cost (biomass only) correlate with intuitive expectations. The results of this effort contribute to a much larger issue: validation of SPURR. Such a study has practical applications for engineering improvements in solar technologies and is useful as a planning tool in the R and D allocation process.

  19. Highly Sensitive Optical Receivers

    CERN Document Server

    Schneider, Kerstin

    2006-01-01

    Highly Sensitive Optical Receivers primarily treats the circuit design of optical receivers with external photodiodes. Continuous-mode and burst-mode receivers are compared. The monograph first summarizes the basics of III/V photodetectors, transistor and noise models, bit-error rate, sensitivity and analog circuit design, thus enabling readers to understand the circuits described in the main part of the book. In order to cover the topic comprehensively, detailed descriptions of receivers for optical data communication in general and, in particular, optical burst-mode receivers in deep-sub-µm CMOS are presented. Numerous detailed and elaborate illustrations facilitate better understanding.

  20. Luminescence sensitivity changes in quartz

    CERN Document Server

    Wintle, A G

    1999-01-01

    In the luminescence dating of sedimentary or heated quartz, some heat treatment is usually applied to the sample immediately prior to the measurement of the optically stimulated luminescence. In this paper we report experiments on a 30,000-year-old sedimentary quartz, in which we use the luminescence response to a test dose to monitor the changes in sensitivity that are caused by holding the quartz at temperatures from 160 to 280 deg. C for times from 10 s to 22 h. For an optically bleached sample, the monitoring is by both optically stimulated luminescence and the 110 deg. C TL peak; both luminescence signals are shown to have the same sensitisation (i.e. activation energy) characteristics. For natural or laboratory irradiated samples only the 110 deg. C TL peak can be used; sensitivity increases of up to a factor of 1.3 and 3 are observed for the natural and laboratory irradiated aliquots, respectively. Up to four exponential components are used to deconvolve the sensitivity change data; the dominant compon...

  1. Feedback-enhanced sensitivity in optomechanics

    DEFF Research Database (Denmark)

    Harris, Glen I.; Andersen, Ulrik L.; Knittel, Joachim

    2012-01-01

    The intracavity power, and hence sensitivity, of optomechanical sensors is commonly limited by parametric instability. Here we characterize the degradation of sensitivity induced by parametric instability in a micron-scale cavity optomechanical system. Feedback via optomechanical transduction...... and electrical gradient force actuation is applied to suppress the parametric instability. As a result a 5.4-fold increase in mechanical motion transduction sensitivity is achieved to a final value of 1.9×10-18 mHz-1/2....

  2. Fundamental Physics Microgravity Sensitivity

    Science.gov (United States)

    Israelsson, Ulf

    1998-01-01

    An introduction followed by a brief discussion about the sensitivity to microgravity environment disturbances for some recent and planned experiments in microgravity fundamental physics will be presented. In particular, correlation between gravity disturbances and the quality of science data sets measured by the Confined Helium Experiment (CHEX) during ground testing and during the November 1997 USMP-4 flight will be described.

  3. Multiple Chemical Sensitivity

    DEFF Research Database (Denmark)

    Junge, Anne Gram

    Et voksende antal mennesker i Danmark oplever at være overfølsomme over for dufte og kemikalier. Imidlertid er den tilskrevne diagnose Multiple Chemical Sensitivity (MCS) ikke medicinsk anerkendt i Danmark pga. mangel på organiske og patofysiologisk basis for symptomerne. Dette speciale bygger på...

  4. Sensitive hydrogen leak detector

    Science.gov (United States)

    Myneni, Ganapati Rao

    1999-01-01

    A sensitive hydrogen leak detector system using passivation of a stainless steel vacuum chamber for low hydrogen outgassing, a high compression ratio vacuum system, a getter operating at 77.5 K and a residual gas analyzer as a quantitative hydrogen sensor.

  5. High-Sensitivity Spectrophotometry.

    Science.gov (United States)

    Harris, T. D.

    1982-01-01

    Selected high-sensitivity spectrophotometric methods are examined, and comparisons are made of their relative strengths and weaknesses and the circumstances for which each can best be applied. Methods include long path cells, noise reduction, laser intracavity absorption, thermocouple calorimetry, photoacoustic methods, and thermo-optical methods.…

  6. Genes contributing to pain sensitivity in the normal population

    DEFF Research Database (Denmark)

    Williams, Frances M.K.; Scollen, Serena; Cao, Dandan

    2012-01-01

    Sensitivity to pain varies considerably between individuals and is known to be heritable. Increased sensitivity to experimental pain is a risk factor for developing chronic pain, a common and debilitating but poorly understood symptom. To understand mechanisms underlying pain sensitivity and to s...

  7. Role of non-enzymatic protein glycation in methylglyoxal-increased the sensitivity of cardiomyocytes to ;hypoxia/reoxygenation injury%蛋白质非酶糖化在丙酮醛促进心肌细胞缺氧/复氧损伤敏感性增加中的作用

    Institute of Scientific and Technical Information of China (English)

    姚雪莉; 王瑾; 杨啸; 张炜芳; 赵焕新; 焦向英; 刘慧荣; 王晓樑

    2013-01-01

    Objective To investigate whether protein glycation increases the injury of myocardial cells subjected to hypoxia/reoxygenation. Methods The cultured H9C2 cells were incubated for 6 days with PBS, Methylglyoxal, and Methylglyoxal+Aminoguanidine, respectively. Then the cells were treated by hypoxia/reoxygenation, and the survival rates of cardiomyocytes in each group were detected by MTT method. LDH release and MDA content were determined in each group. AGEs contents in cells treated with PBS, MGO or MGO+AG were assayed by immunohistochemical staining. Results Preculturing cardiomyocytes with MG for 6 days caused a significant increase in AGEs production, which was dramatically reduced by cotreatment with AG, a strong AGEs formation inhibitor, and preculturing cardiomyocytes with MG for 6 days made cardiomyocytes more susceptible to H/R, as evidenced by decreased survival rate of cells and LDH release. Conclusion Protein glycation sensitized cultured cardiomyocytes to H/R injury, and therapeutic interventions inhibitting AGEs formation may attenuate ischemic-reperfusion injury in hyperglycemic state diseases such as diabetes.%目的:观察蛋白质非酶糖化是否会增加心肌缺氧/复氧损伤的敏感性。方法常规培养H9C2细胞,分别给予PBS(对照组)、丙酮醛(200μmol/L)、丙酮醛(200μmol/L)+氨基胍(100μmol/L)孵育6 d后接受缺氧/复氧处理,以MTT法测定心肌细胞存活率,微量酶活性测试法检测乳酸脱氢酶(LDH)释放变化,比色法检测丙二醛(MDA)含量,并通过免疫组织化学检测心肌细胞终末糖化晚期产物(AGEs)表达。结果缺氧/复氧降低细胞存活率,增加心肌细胞MDA含量和LDH释放;而丙酮醛处理6 d的心肌细胞的AGEs含量明显增加,并对缺氧/复氧损伤的敏感性增加,与PBS孵育细胞经缺氧/复氧处理后相比, MDA含量和LDH释放显著上升,存活率明显下降(P<0.01);MGO引起的上述

  8. Salt sensitivity correlates positively with insulin sensitivity in healthy volunteers

    NARCIS (Netherlands)

    ter Maaten, JC; Voordouw, JJ; Bakker, SJL; Gans, ROB

    1999-01-01

    Background The aim of the study was to assess the relationship between insulin sensitivity and salt sensitivity in healthy subjects who display a wide range of insulin sensitivity. As a secondary objective, we assessed the relationship between salt sensitivity and the other characteristics of the in

  9. Sensitivity-increasing effect of recommbinant analgesic-antitumor peptide on cholangiocarcinoma cells to chemotherapy%重组东亚钳蝎镇痛抗肿瘤肽对胆管癌细胞化疗的增敏作用

    Institute of Scientific and Technical Information of China (English)

    葛贤秀; 曹鹏; 缪林; 李全鹏; 汪婷婷; 于泓; 季国忠

    2013-01-01

    目的 探讨重组东亚钳蝎镇痛抗肿瘤肽(rAGAP)对胆管癌细胞化疗的增敏作用及其机制.方法 体外培养人胆管癌细胞株HuCC-T1、QBC939和胆管上皮细胞HIBepic,单独用药:不同浓度的rAGAP、顺铂(DDP)和5-氟尿嘧啶(5-FU)处理三株细胞,四甲基偶氮唑盐比色法(MTT法)观察细胞的增殖抑制率及半抑制浓度(IC50).联合用药:选用rAGAP(5μg/ml)、DDP(4μg/ml)、5-FU(50μg/ml)处理三株细胞,分为对照(A)组、rAGAP(B)组、DDP(C)组、rAGAP与DDP联用(D)组、5-FU(E)组、rAGAP与5-FU联用(F)组.MTT法检测细胞存活率;荧光定量PCR方法检测细胞多药耐药基因1(MDR-1)及多药耐药相关蛋白1(MRP-1)的mRNA表达.结果 单独用药结果显示rAGAP抑制细胞增殖呈时间剂量依赖性,且对癌细胞具有一定的选择性;rAGAP组的IC50值明显小于DDP组和5-FU组(P<0.01).联合用药结果显示,胆管癌细胞株HuCC-T1和QBC939中,D组较B、C组以及F组较B、E组细胞存活减少;而且MDR-1和MRP-1表达下调(P<0.01).而在胆管上皮细胞HIBepic细胞系里,联合用药并未表现明显的增加化疗药效果的作用.结论 rAGAP可选择性抑制胆管癌细胞,与化疗药DDP和5 FU联用可增强化疗敏感性.%Objective To investigate the sensitivity-increasing effect of recommbinant analgesicantitumor peptide (rAGAP)on cholangiocarcinoma cells to chemotherapy and its underlying mechanism.Methods The cholangiocarcinoma cell lines HuCC-T1,QBC939 and bile duct epithelial cells HIBepic were cultured in vitro,and then exposed to rAGAP,cisplatin and 5-FU,respectively.The cells inhibition rate and 50% inhibiting concentration(IC5) were detected.The cells were divided into 6 groups of A(control),B(treated with rAGAP 5 μg/ml),C(treated with DDP 4μg/ml),D(treated with 5-FU 50μg/ml plus DDP),E(treated with 5-FU 50μg/ml) and F(treated with rAGAP plus 5FU).The cell survival rates were detected using MTT method and the mRNA expressions of

  10. COLOR- SENSITIZED SOLAR ELEMENTS

    Directory of Open Access Journals (Sweden)

    Gish R. A.

    2016-05-01

    Full Text Available Photovoltaic devices are a promising solution to the energy crisis, because they generate electricity directly from sunlight, without producing CO2. While color-sensitized batteries are the most studied element, mainly due to its low cost and high efficiency solar energy conversion into electricity. Until recently, the color-sensitized solar cells performance was less than 1%, however, the use of titanium dioxide as the anode material have greatly raised their efficiency. The advantages of titanium dioxide is primarily in the low cost, but its use provides high light capture efficiency, with external quantum efficiency (efficiency incident photon - charge, usually in the range of 60-90% using nanocrystal forms in comparison with

  11. Culturally sensitive assessment.

    Science.gov (United States)

    Edwards, C P; Kumru, A

    1999-04-01

    Issues of cultural interaction and culturally sensitive assessment and treatment of young children have become prominent in recent years for mental health professionals, for reasons having to do with changing demographics, public values, and professional vision. "Culture" refers to the sociocultural adaptation of design for living shared by people as members of a community. Mental health professionals who work with culturally diverse populations need to become culturally self-aware and find abstract and experiential ways to build a useful body of professional knowledge concerning childrearing and discipline practices, health and illness beliefs, communication styles, and expectations about family or professional relations or other group interactions. They also need to learn how to work effectively in intercultural teams, use families as partners and resources, train and work with interpreters, and select and use formal and nonformal assessment procedures in appropriate, culturally sensitive ways.

  12. Developing cultural sensitivity

    DEFF Research Database (Denmark)

    Ruddock, Heidi; Turner, deSalle

    2007-01-01

    comfortable with the experience of making a transition from one culture to another, making adjustments to cultural differences, and growing personally. Central to this process was the students’ experience of studying in an unfamiliar environment, experiencing stress and varying degrees of culture shock......Title. Developing cultural sensitivity: nursing students’ experiences of a study abroad programme Aim. This paper is a report of a study to explore whether having an international learning experience as part of a nursing education programme promoted cultural sensitivity in nursing students....... The findings suggest that study abroad is a useful strategy for bridging the theory–practice divide. However, further research is needed with larger and more diverse students to test the generalizability of the findings. Longitudinal research is also needed to assess the impact of study abroad programmes...

  13. Density Sensitive Hashing

    CERN Document Server

    Lin, Yue; Li, Cheng

    2012-01-01

    Nearest neighbors search is a fundamental problem in various research fields like machine learning, data mining and pattern recognition. Recently, hashing-based approaches, e.g., Locality Sensitive Hashing (LSH), are proved to be effective for scalable high dimensional nearest neighbors search. Many hashing algorithms found their theoretic root in random projection. Since these algorithms generate the hash tables (projections) randomly, a large number of hash tables (i.e., long codewords) are required in order to achieve both high precision and recall. To address this limitation, we propose a novel hashing algorithm called {\\em Density Sensitive Hashing} (DSH) in this paper. DSH can be regarded as an extension of LSH. By exploring the geometric structure of the data, DSH avoids the purely random projections selection and uses those projective functions which best agree with the distribution of the data. Extensive experimental results on real-world data sets have shown that the proposed method achieves better ...

  14. Solving tooth sensitivity.

    Science.gov (United States)

    Miller, Michael B

    2010-01-01

    Solving tooth sensitivity requires both you and the patients to be resilient and to understand that if one approach doesn't work, you can try another one that is non-invasive or, at worst, minimally invasive. Much like the clinician who posted the original question, I strongly believe that it is our responsibility to convince patients that jumping to a radical solution could be totally unnecessary--and expensive-- and still might not solve the problem.

  15. Integrated Sensitivity Analysis Workflow

    Energy Technology Data Exchange (ETDEWEB)

    Friedman-Hill, Ernest J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hoffman, Edward L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gibson, Marcus J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Clay, Robert L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-08-01

    Sensitivity analysis is a crucial element of rigorous engineering analysis, but performing such an analysis on a complex model is difficult and time consuming. The mission of the DART Workbench team at Sandia National Laboratories is to lower the barriers to adoption of advanced analysis tools through software integration. The integrated environment guides the engineer in the use of these integrated tools and greatly reduces the cycle time for engineering analysis.

  16. Quantification of adipose tissue insulin sensitivity.

    Science.gov (United States)

    Søndergaard, Esben; Jensen, Michael D

    2016-06-01

    In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and weaknesses.

  17. Exquisite light sensitivity of Drosophila melanogaster cryptochrome.

    Directory of Open Access Journals (Sweden)

    Pooja Vinayak

    Full Text Available Drosophila melanogaster shows exquisite light sensitivity for modulation of circadian functions in vivo, yet the activities of the Drosophila circadian photopigment cryptochrome (CRY have only been observed at high light levels. We studied intensity/duration parameters for light pulse induced circadian phase shifts under dim light conditions in vivo. Flies show far greater light sensitivity than previously appreciated, and show a surprising sensitivity increase with pulse duration, implying a process of photic integration active up to at least 6 hours. The CRY target timeless (TIM shows dim light dependent degradation in circadian pacemaker neurons that parallels phase shift amplitude, indicating that integration occurs at this step, with the strongest effect in a single identified pacemaker neuron. Our findings indicate that CRY compensates for limited light sensitivity in vivo by photon integration over extraordinarily long times, and point to select circadian pacemaker neurons as having important roles.

  18. High sensitivity knitted fabric strain sensors

    Science.gov (United States)

    Xie, Juan; Long, Hairu; Miao, Menghe

    2016-10-01

    Wearable sensors are increasingly used in smart garments for detecting and transferring vital signals and body posture, movement and respiration. Existing fabric strain sensors made from metallized yarns have low sensitivity, poor comfort and low durability to washing. Here we report a knitted fabric strain sensor made from a cotton/stainless steel (SS) fibre blended yarn which shows much higher sensitivity than sensors knitted from metallized yarns. The fabric feels softer than pure cotton textiles owing to the ultrafine stainless steel fibres and does not lose its electrical property after washing. The reason for the high sensitivity of the cotton/SS knitted fabric sensor was explored by comparing its sensing mechanism with the knitted fabric sensor made from metallized yarns. The results show that the cotton/SS yarn-to-yarn contact resistance is highly sensitive to strain applied to hooked yarn loops.

  19. Exquisite Light Sensitivity of Drosophila melanogaster Cryptochrome

    Science.gov (United States)

    Vinayak, Pooja; Coupar, Jamie; Hughes, S. Emile; Fozdar, Preeya; Kilby, Jack; Garren, Emma; Yoshii, Taishi; Hirsh, Jay

    2013-01-01

    Drosophila melanogaster shows exquisite light sensitivity for modulation of circadian functions in vivo, yet the activities of the Drosophila circadian photopigment cryptochrome (CRY) have only been observed at high light levels. We studied intensity/duration parameters for light pulse induced circadian phase shifts under dim light conditions in vivo. Flies show far greater light sensitivity than previously appreciated, and show a surprising sensitivity increase with pulse duration, implying a process of photic integration active up to at least 6 hours. The CRY target timeless (TIM) shows dim light dependent degradation in circadian pacemaker neurons that parallels phase shift amplitude, indicating that integration occurs at this step, with the strongest effect in a single identified pacemaker neuron. Our findings indicate that CRY compensates for limited light sensitivity in vivo by photon integration over extraordinarily long times, and point to select circadian pacemaker neurons as having important roles. PMID:23874218

  20. Increased chromosome radiosensitivity during pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Ricoul, Michelle; Sabatier, Laure; Dutrillaux, Bernard [Commissariat a l`Energie Atomique, Laboratoire de Radiobiologie et Oncologie, DRR, DSV, Fontenay aux roses (France)

    1997-03-04

    It was necessary to consider the risks of exposure of pregnant women, not only in relation to the child, but also in relation to their own hypersensitivity. We have demonstrated that pregnancy increases radiosensitivity of chromosome in the mouse at the end of gestation. This is of importance since it may have implications on radioprotection of pregnant women and give experimental guidelines to the problems of hypersensitivity to drugs and cancer aggravation during pregnancy. Blood obtained from women at various times of pregnancy was exposed to ionizing radiations. By comparison to non-pregnant women, an increase in chromosome breakage was observed in metaphases from lymphocytes, after short-term culture in the presence of the serum of the same donor. Immediately after delivery, this increase in radiosensitivity disappeared. In a prospective study, serial analyses showed a very strong correlation between the amount of pregnancy hormones, progesterone in particular, and the increase in radiosensitivity. Pregnant women may have an increased sensitivity to ionizing radiation during the second half of their pregnancy. This study provides the first evidence in human that radiosensitivity may vary in relation to physiological conditions.

  1. Dye sensitized solar cells.

    Science.gov (United States)

    Wei, Di

    2010-03-16

    Dye sensitized solar cell (DSSC) is the only solar cell that can offer both the flexibility and transparency. Its efficiency is comparable to amorphous silicon solar cells but with a much lower cost. This review not only covers the fundamentals of DSSC but also the related cutting-edge research and its development for industrial applications. Most recent research topics on DSSC, for example, applications of nanostructured TiO(2), ZnO electrodes, ionic liquid electrolytes, carbon nanotubes, graphene and solid state DSSC have all been included and discussed.

  2. Dye Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Di Wei

    2010-03-01

    Full Text Available Dye sensitized solar cell (DSSC is the only solar cell that can offer both the flexibility and transparency. Its efficiency is comparable to amorphous silicon solar cells but with a much lower cost. This review not only covers the fundamentals of DSSC but also the related cutting-edge research and its d