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Sample records for activation profiles depending

  1. Profiling of Sox4-dependent transcriptome in skin links tumour suppression and adult stem cell activation

    Miguel Foronda

    2015-12-01

    Full Text Available Adult stem cells (ASCs reside in specific niches in a quiescent state in adult mammals. Upon specific cues they become activated and respond by self-renewing and differentiating into newly generated specialised cells that ensure appropriate tissue fitness. ASC quiescence also serves as a tumour suppression mechanism by hampering cellular transformation and expansion (White AC et al., 2014. Some genes restricted to early embryonic development and adult stem cell niches are often potent modulators of stem cell quiescence, and derailed expression of these is commonly associated to cancer (Vervoort SJ et al., 2013. Among them, it has been shown that recommissioned Sox4 expression facilitates proliferation, survival and migration of malignant cells. By generating a conditional Knockout mouse model in stratified epithelia (Sox4cKO mice, we demonstrated a delayed plucking-induced Anagen in the absence of Sox4. Skin global transcriptome analysis revealed a prominent defect in the induction of transcriptional networks that control hair follicle stem cell (HFSC activation such as those regulated by Wnt/Ctnnb1, Shh, Myc or Sox9, cell cycle and DNA damage response-associated pathways. Besides, Sox4cKO mice are resistant to skin carcinogenesis, thus linking Sox4 to both normal and pathological HFSC activation (Foronda M et al., 2014. Here we provide additional details on the analysis of Sox4-regulated transcriptome in Telogen and Anagen skin. The raw and processed microarray data is deposited in GEO under GSE58155.

  2. Profiling of Sox4-dependent transcriptome in skin links tumour suppression and adult stem cell activation.

    Foronda, Miguel; Morgado-Palacin, Lucia; Gómez-López, Gonzalo; Domínguez, Orlando; Pisano, David G; Blasco, Maria A

    2015-12-01

    Adult stem cells (ASCs) reside in specific niches in a quiescent state in adult mammals. Upon specific cues they become activated and respond by self-renewing and differentiating into newly generated specialised cells that ensure appropriate tissue fitness. ASC quiescence also serves as a tumour suppression mechanism by hampering cellular transformation and expansion (White AC et al., 2014). Some genes restricted to early embryonic development and adult stem cell niches are often potent modulators of stem cell quiescence, and derailed expression of these is commonly associated to cancer (Vervoort SJ et al., 2013). Among them, it has been shown that recommissioned Sox4 expression facilitates proliferation, survival and migration of malignant cells. By generating a conditional Knockout mouse model in stratified epithelia (Sox4 (cKO) mice), we demonstrated a delayed plucking-induced Anagen in the absence of Sox4. Skin global transcriptome analysis revealed a prominent defect in the induction of transcriptional networks that control hair follicle stem cell (HFSC) activation such as those regulated by Wnt/Ctnnb1, Shh, Myc or Sox9, cell cycle and DNA damage response-associated pathways. Besides, Sox4 (cKO) mice are resistant to skin carcinogenesis, thus linking Sox4 to both normal and pathological HFSC activation (Foronda M et al., 2014). Here we provide additional details on the analysis of Sox4-regulated transcriptome in Telogen and Anagen skin. The raw and processed microarray data is deposited in GEO under GSE58155. PMID:26697322

  3. Profiling of Substrates for Zinc‐dependent Lysine Deacylase Enzymes: HDAC3 Exhibits Decrotonylase Activity In Vitro

    Madsen, Andreas Stahl; Olsen, Christian Adam

    2012-01-01

    Systematic screening of the activities of the eleven human zinc-dependent lysine deacylases against a series of fluorogenic substrates (see scheme) as well as kinetic evaluation revealed substrates for screenings of histone deacetylases HDAC10 and HDAC11 at reasonably low enzyme concentrations...

  4. Profile sampling dependence of the MLAYER program.

    Chang, Ting-Hsun

    1991-01-01

    Approved for public release; distribution is unlimited The dependence of the predictions of the MLAYER program on the set of heights at which the refractive index value are sampled from a fixed reference profile are analyzed. A refractivity profile with a four-meter evaporation duct is adopted as a reference. Two variable piecewise linear profiles of four and five segments, respectively, are used to approximate the reference profile for MLAYER computations. The sensitivities...

  5. Profile sampling dependence of the MLAYER program

    Chang, Ting-Hsun

    1991-03-01

    The dependence of the predictions of the MLAYER program on the set of heights at which the refractive index value are sampled from a fixed reference profile are analyzed. A refractivity profile with a four-meter evaporation duct is adopted as a reference. Two variable piecewise linear profiles of four and five segments, respectively, are used to approximate the reference profile for MLAYER computations. The sensitivities of the waveguide mode location, the range attenuation rate, and the height-gain function to the changes of the piece-wise linear profiles are investigated at the frequencies 3, 6, 10, and 15 GHz. The frequency dependence of the dominant mode for one profile is also studied to investigate the fact that the sensitivity to changes in sampling point location is lower at GHz than at other frequencies. A general rule-of-thumb for the change in range attenuation rate due to a slight change in refractivity is suggested.

  6. Temporal profiles of age-dependent changes in cytokine mRNA expression and glial cell activation after status epilepticus in postnatal rat hippocampus

    Ruohonen Saku

    2011-04-01

    Full Text Available Abstract Background Status epilepticus (SE is proposed to lead to an age-dependent acute activation of a repertoire of inflammatory processes, which may contribute to neuronal damage in the hippocampus. The extent and temporal profiles of activation of these processes are well known in the adult brain, but less so in the developing brain. We have now further elucidated to what extent inflammation is activated by SE by investigating the acute expression of several cytokines and subacute glial reactivity in the postnatal rat hippocampus. Methods SE was induced by an intraperitoneal (i.p. injection of kainic acid (KA in 9- and 21-day-old (P9 and P21 rats. The mRNA expression of interleukin-1 beta (IL-1β, tumor necrosis factor-alpha (TNF-α, interleukin-10 (IL-10, matrix metalloproteinase-9 (MMP-9, glial-derived neurotrophic factor (GDNF, interferon gamma (IFN-γ, and transforming growth factor-beta 1 (TGF-β1 were measured from 4 h up to 3 days after KA injection with real-time quantitative PCR (qPCR. IL-1β protein expression was studied with ELISA, GFAP expression with western blotting, and microglial and astrocyte morphology with immunohistochemistry 3 days after SE. Results SE increased mRNA expression of IL-1β, TNF-α and IL-10 mRNA in hippocampus of both P9 and P21 rats, their induction being more rapid and pronounced in P21 than in P9 rats. MMP-9 expression was augmented similarly in both age groups and GDNF expression augmented only in P21 rats, whereas neither IFN-γ nor TGF-β1 expression was induced in either age group. Microglia and astrocytes exhibited activated morphology in the hippocampus of P21 rats, but not in P9 rats 3 d after SE. Microglial activation was most pronounced in the CA1 region and also detected in the basomedial amygdala. Conclusion Our results suggest that SE provokes an age-specific cytokine expression in the acute phase, and age-specific glial cell activation in the subacute phase as verified now in the

  7. Parametric dependencies of JET electron temperature profiles

    Schunke, B. [Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking; Imre, K.; Riedel, K. [New York Univ., NY (United States)

    1994-07-01

    The JET Ohmic, L-Mode and H-Mode electron temperature profiles obtained from the LIDAR Thomson Scattering Diagnostic are parameterized in terms of the normalized flux parameter and a set of the engineering parameters like plasma current, toroidal field, line averages electron density... It is shown that the electron temperature profiles fit a log-additive model well. It is intended to use the same model to predict the profile shape for D-T discharges in JET and in ITER. 2 refs., 5 figs.

  8. PROFILE OF LIVER DYSFUNCTION IN ALCHOHOL DEPENDENCE

    Desai, N.G.; Vaswani, M.; Chavan, B.S.; Tripathi, B.M.; Kaw, N.

    1996-01-01

    Ninety two patients of alcohol dependence were studied for liver function at a specialised drug dependence treatment centre. Biochemical laboratory evidence of liver dysfunction was found in a very large number of patients, including the patients who had no clinical signs or symptoms. The findings from this retrospective study are discussed in the context of the earlier studies from other settings in India.

  9. Profile of liver dysfunction in alchohol dependence.

    Desai, N G; Vaswani, M; Chavan, B S; Tripathi, B M; Kaw, N

    1996-01-01

    Ninety two patients of alcohol dependence were studied for liver function at a specialised drug dependence treatment centre. Biochemical laboratory evidence of liver dysfunction was found in a very large number of patients, including the patients who had no clinical signs or symptoms. The findings from this retrospective study are discussed in the context of the earlier studies from other settings in India. PMID:21584115

  10. Radiosensitivity profiles from a panel of ovarian cancer cell lines exhibiting genetic alterations in p53 and disparate DNA-dependent protein kinase activities

    Langland, Gregory T.; Yannone, Steven M.; Langland, Rachel A.; Nakao, Aki; Guan, Yinghui; Long, Sydney B.T.; Vonguyen, Lien; Chen, David J.; Gray, Joe W; Chen, Fanqing

    2009-09-07

    The variability of radiation responses in ovarian tumors and tumor-derived cell lines is poorly understood. Since both DNA repair capacity and p53 status can significantly alter radiation sensitivity, we evaluated these factors along with radiation sensitivity in a panel of sporadic human ovarian carcinoma cell lines. We observed a gradation of radiation sensitivity among these sixteen lines, with a five-fold difference in the LD50 between the most radiosensitive and the most radioresistant cells. The DNA-dependent protein kinase (DNA-PK) is essential for the repair of radiation induced DNA double-strand breaks in human somatic cells. Therefore, we measured gene copy number, expression levels, protein abundance, genomic copy and kinase activity for DNA-PK in all of our cell lines. While there were detectable differences in DNA-PK between the cell lines, there was no clear correlation with any of these differences and radiation sensitivity. In contrast, p53 function as determined by two independent methods, correlated well with radiation sensitivity, indicating p53 mutant ovarian cancer cells are typically radioresistant relative to p53 wild-type lines. These data suggest that the activity of regulatory molecules such as p53 may be better indicators of radiation sensitivity than DNA repair enzymes such as DNAPK in ovarian cancer.

  11. Size-dependent mortality rate profiles.

    Roa-Ureta, Ruben H

    2016-08-01

    Knowledge of mortality rates is crucial to the understanding of population dynamics in populations of free-living fish and invertebrates in marine and freshwater environments, and consequently to sustainable resource management. There is a well developed theory of population dynamics based on age distributions that allow direct estimation of mortality rates. However, for most cases the aging of individuals is difficult or age distributions are not available for other reasons. The body size distribution is a widely available alternative although the theory underlying the formation of its shape is more complicated than in the case of age distributions. A solid theory of the time evolution of a population structured by any physiological variable has been developed in 1960s and 1970s by adapting the Hamilton-Jacobi formulation of classical mechanics, and equations to estimate the body size-distributed mortality profile have been derived for simple cases. Here I extend those results with regards to the size-distributed mortality profile to complex cases of non-stationary populations, individuals growing according to a generalised growth model and seasonally patterned recruitment pulses. I apply resulting methods to two cases in the marine environment, a benthic crustacean population that was growing during the period of observation and whose individuals grow with negative acceleration, and a sea urchin coastal population that is undergoing a stable cycle of two equilibrium points in population size whose individuals grow with varying acceleration that switches sign along the size range. The extension is very general and substantially widens the applicability of the theory. PMID:27164999

  12. On active current selection for Lagrangian profilers

    Jouffroy, Jerome; Zhou, Qiuyang; Zielinski, Oliver

    2013-01-01

    Autonomous Lagrangian profilers are now widely used as measurement and monitoring platforms, notably in observation programs as Argo. In a typical mode of operation, the profilers drift passively at their parking depth before making a vertical profile to go back to the surface. This paper presents...... simple and computationally-efficient control strategies to actively select and use ocean currents so that a profiler can autonomously reach a desired destination. After briefly presenting a typical profiler and possible mechanical modifications for a coastal environment, we introduce simple mathematical...

  13. Dependence of adiabatic population transfer on pulse profile

    S Dasgupta; T kushwaha; D Goswami

    2006-06-01

    Control of population transfer by rapid adiabatic passage has been an established technique wherein the exact amplitude profile of the shaped pulse is considered to be insignificant. We study the effect of ultrafast shaped pulses for two-level systems, by density-matrix approach. However, we find that adiabaticity depends simultaneously on pulse profile as well as the frequency modulation under non-resonant conditions.

  14. Crack depth profiling using guided wave angle dependent reflectivity

    Tomographic corrosion monitoring techniques have been developed, using two rings of sensors around the circumference of a pipe. This technique is capable of providing a detailed wall thickness map, however this might not be the only type of structural damage. Therefore this concept is expanded to detect and size cracks and small corrosion defects like root corrosion. The expanded concept uses two arrays of guided-wave transducers, collecting both reflection and transmission data. The data is processed such that the angle-dependent reflectivity is obtained without using a baseline signal of a defect-free situation. The angle-dependent reflectivity is the input of an inversion scheme that calculates a crack depth profile. From this profile, the depth and length of the crack can be determined. Preliminary experiments show encouraging results. The depth sizing accuracy is in the order of 0.5 mm

  15. Using Activity Metrics for DEVS Simulation Profiling

    Muzy A.

    2014-01-01

    Full Text Available Activity metrics can be used to profile DEVS models before and during the simulation. It is critical to get good activity metrics of models before and during their simulation. Having a means to compute a-priori activity of components (analytic activity may be worth when simulating a model (or parts of it for the first time. After, during the simulation, analytic activity can be corrected using dynamic one. In this paper, we introduce McCabe cyclomatic complexity metric (MCA to compute analytic activity. Both static and simulation activity metrics have been implemented through a plug-in of the DEVSimPy (DEVS Simulator in Python language environment and applied to DEVS models.

  16. Activity-Based Protein Profiling of Microbes

    Sadler, Natalie C.; Wright, Aaron T.

    2015-02-01

    Activity-Based Protein Profiling (ABPP) in conjunction with multimodal characterization techniques has yielded impactful findings in microbiology, particularly in pathogen, bioenergy, drug discovery, and environmental research. Using small molecule chemical probes that react irreversibly with specific proteins or protein families in complex systems has provided insights in enzyme functions in central metabolic pathways, drug-protein interactions, and regulatory protein redox, for systems ranging from photoautotrophic cyanobacteria to mycobacteria, and combining live cell or cell extract ABPP with proteomics, molecular biology, modeling, and other techniques has greatly expanded our understanding of these systems. New opportunities for application of ABPP to microbial systems include: enhancing protein annotation, characterizing protein activities in myriad environments, and reveal signal transduction and regulatory mechanisms in microbial systems.

  17. Strain-dependent profile of misfolded prion protein aggregates.

    Morales, Rodrigo; Hu, Ping Ping; Duran-Aniotz, Claudia; Moda, Fabio; Diaz-Espinoza, Rodrigo; Chen, Baian; Bravo-Alegria, Javiera; Makarava, Natallia; Baskakov, Ilia V; Soto, Claudio

    2016-01-01

    Prions are composed of the misfolded prion protein (PrP(Sc)) organized in a variety of aggregates. An important question in the prion field has been to determine the identity of functional PrP(Sc) aggregates. In this study, we used equilibrium sedimentation in sucrose density gradients to separate PrP(Sc) aggregates from three hamster prion strains (Hyper, Drowsy, SSLOW) subjected to minimal manipulations. We show that PrP(Sc) aggregates distribute in a wide range of arrangements and the relative proportion of each species depends on the prion strain. We observed a direct correlation between the density of the predominant PrP(Sc) aggregates and the incubation periods for the strains studied. The relative presence of PrP(Sc) in fractions of different sucrose densities was indicative of the protein deposits present in the brain as analyzed by histology. Interestingly, no association was found between sensitivity to proteolytic degradation and aggregation profiles. Therefore, the organization of PrP molecules in terms of the density of aggregates generated may determine some of the particular strain properties, whereas others are independent from it. Our findings may contribute to understand the mechanisms of strain variation and the role of PrP(Sc) aggregates in prion-induced neurodegeneration. PMID:26877167

  18. Passion and dependency in online shopping activities.

    Wang, Chih-Chien; Yang, Hui-Wen

    2007-04-01

    This study examines the influence of harmonious passion (HP) and obsessive passion (OP) to online shopping dependency. The results show that both HP and OP might lead to online shopping dependency and online shoppers with OP are more dependent on online shopping activities. In addition, this study also found out that HP and OP could be denoted as a sequence of different intensities of passion, where HP might be a necessity of OP. PMID:17474850

  19. Plasma parameter dependences of the electron density profile in TEXT

    A multichannel, heterodyne, far-infrared laser interferometer with high spatial and phase resolution is employed on TEXT to characterize the equilibrium density profile for the full range of TEXT discharge parameters. Gaussian and parabolic functional fits with three free parameters are made to the measured profiles and compared. Scaling of the equilibrium density profile shape with plasma current, toroidal magnetic field, and density is clearly observed. By performing a regression analysis on each free parameter for the functional fit, one can construct a set of analytical relations describing the TEXT density profile for steady-state ohmic discharges. The database used to identify these relations contains 50 different discharge conditions

  20. On Active Current Selection for Lagrangian Profilers

    J. Jouffroy

    2013-01-01

    Full Text Available Autonomous Lagrangian profilers are now widely used as measurement and monitoring platforms, notably in observation programs as Argo. In a typical mode of operation, the profilers drift passively at their parking depthbefore making a vertical profile to go back to the surface. This paperpresents simple and computationally-efficient control strategies to activelyselect and use ocean currents so that a profiler can autonomously reach adesired destination. After briefly presenting a typical profiler andpossible mechanical modifications for a coastal environment, we introducesimple mathematical models for the profiler and the currents it will use. Wethen present simple feedback controllers that, using the direction of thecurrents and taking into account the configuration of the environment(coastal or deep-sea, is able to steer the profiler to any desiredhorizontal location. To illustrate the approach, a few results are presentedusing both simulated currents and real current velocity profiles from theNorth Sea.

  1. Cohort Profile: The Nicotine Dependence in Teens (NDIT) Study.

    O'Loughlin, Jennifer; Dugas, Erika N; Brunet, Jennifer; DiFranza, Joseph; Engert, James C; Gervais, Andre; Gray-Donald, Katherine; Karp, Igor; Low, Nancy C; Sabiston, Catherine; Sylvestre, Marie-Pierre; Tyndale, Rachel F; Auger, Nathalie; Auger, Nathalie; Mathieu, Belanger; Tracie, Barnett; Chaiton, Michael; Chenoweth, Meghan J; Constantin, Evelyn; Contreras, Gisèle; Kakinami, Lisa; Labbe, Aurelie; Maximova, Katerina; McMillan, Elizabeth; O'Loughlin, Erin K; Pabayo, Roman; Roy-Gagnon, Marie-Hélène; Tremblay, Michèle; Wellman, Robert J; Hulst, Andraeavan; Paradis, Gilles

    2015-10-01

    The Nicotine Dependence in Teens (NDIT) study is a prospective cohort investigation of 1294 students recruited in 1999-2000 from all grade 7 classes in a convenience sample of 10 high schools in Montreal, Canada. Its primary objectives were to study the natural course and determinants of cigarette smoking and nicotine dependence in novice smokers. The main source of data was self-report questionnaires administered in class at school every 3 months from grade 7 to grade 11 (1999-2005), for a total of 20 survey cycles during high school education. Questionnaires were also completed after graduation from high school in 2007-08 and 2011-12 (survey cycles 21 and 22, respectively) when participants were aged 20 and 24 years on average, respectively. In addition to its primary objectives, NDIT has embedded studies on obesity, blood pressure, physical activity, team sports, sedentary behaviour, diet, genetics, alcohol use, use of illicit drugs, second-hand smoke, gambling, sleep and mental health. Results to date are described in 58 publications, 20 manuscripts in preparation, 13 MSc and PhD theses and 111 conference presentations. Access to NDIT data is open to university-appointed or affiliated investigators and to masters, doctoral and postdoctoral students, through their primary supervisor (www.nditstudy.ca). PMID:25022274

  2. Activity Dependent Regulation of Inhibitory Circuitry

    Sharma, Nikhil

    2015-01-01

    Inhibition controls information flow through a neural circuit by modulating synaptic integration, restricting action potentials, and coordinating the activity of ensembles of neurons. These functions are mediated by a diverse array of inhibitory neuron subtypes that synapse on defined domains of a postsynaptic neuron. Activity-dependent transcription controls inhibitory synapse number and function, but how this transcription program affects the inhibitory inputs that form on di...

  3. Activity Therapy Services and Chemical Dependency Rehabilitation.

    James, Mark R.; Townsley, Robin K.

    1989-01-01

    Discusses how music, occupational, and recreation therapies can contribute to comprehensive treatment programs for chemical dependency. Sees prime contribution of activity therapy as lying in nature of experiential education, applying insight gained in counseling sessions and discussion groups to practical real-life situations. (Author/NB)

  4. Regional brain activity correlates of nicotine dependence.

    Rose, Jed E; Behm, Frederique M; Salley, Alfred N; Bates, James E; Coleman, R Edward; Hawk, Thomas C; Turkington, Timothy G

    2007-12-01

    Fifteen smokers participated in a study investigating brain correlates of nicotine dependence. Dependence was reduced by having subjects switch to denicotinized cigarettes for 2 weeks while wearing nicotine skin patches. Positron emission tomography (PET) scans assessed regional cerebral metabolic rate for glucose (rCMRglc) after overnight nicotine abstinence on three occasions: (1) at baseline; (2) after 2 weeks of exposure to denicotinized cigarettes+nicotine patches; and (3) 2 weeks after returning to smoking the usual brands of cigarettes. Craving for cigarettes and scores on the Fagerström Test of Nicotine Dependence (FTND) questionnaire decreased at the second session relative to the first and last sessions. Regional brain metabolic activity (normalized to whole brain values) at session 2 also showed a significant decrease in the right hemisphere anterior cingulate cortex. Exploratory post hoc analyses showed that the change in craving across sessions was negatively correlated with the change in rCMRglc in several structures within the brain reward system, including the ventral striatum, orbitofrontal cortex and pons. The between-session difference in thalamus activity (right hemisphere) was positively correlated with the difference in FTND scores. Correlational analyses also revealed that reported smoking for calming effects was associated with a decrease (at session 2) in thalamus activity (bilaterally) and with an increase in amygdala activity (left hemisphere). Reported smoking to enhance pleasurable relaxation was associated with an increase in metabolic activity of the dorsal striatum (caudate, putamen) at session 2. These findings suggest that reversible changes in regional brain metabolic activity occur in conjunction with alterations in nicotine dependence. The results also highlight the likely role of thalamic gating processes as well as striatal reward and corticolimbic regulatory pathways in the maintenance of cigarette addiction. PMID:17356570

  5. Anorexia nervosa depends on adrenal sympathetic hyperactivity: opposite neuroautonomic profile of hyperinsulinism syndrome

    Fuad Lechin

    2010-09-01

    predominance of overwhelming adrenal sympathetic activity over neural sympathetic activity. This combined central and autonomic nervous system profile contrasts with that registered in patients affected by hyperinsulinism, hypoglycemia, and bulimia syndrome which depends on the absolute predominance of neural sympathetic activity.Keywords: anorexia nervosa, adrenal sympathetic activity, adrenaline, noradrenaline, eating disorders

  6. Epoch-dependent absorption line profile variability in lambda Cep

    Uuh-Sonda, J M; Eenens, P; Mahy, L; Palate, M; Gosset, E; Flores, C A

    2014-01-01

    We present the analysis of a multi-epoch spectroscopic monitoring campaign of the O6Ief star lambda Cep. Previous observations reported the existence of two modes of non-radial pulsations in this star. Our data reveal a much more complex situation. The frequency content of the power spectrum considerably changes from one epoch to the other. We find no stable frequency that can unambiguously be attributed to pulsations. The epoch-dependence of the frequencies and variability patterns are similar to what is seen in the wind emission lines of this and other Oef stars, suggesting that both phenomena likely have the same, currently still unknown, origin.

  7. Multicomponent He I 10830 {\\AA} profiles in an active filament

    Sasso, C; Solanki, S K

    2011-01-01

    We present new spectropolarimetric observations of the chromospheric He I 10830 {\\AA} multiplet observed in a filament during its phase of activity. The data were recorded with the new Tenerife Infrared Polarimeter (TIP-II) at the German Vacuum Tower Telescope (VTT) on 2005 May 18. We inverted the He Stokes profiles using multiple atmospheric components. The observed He Stokes profiles display a remarkably wide variety of shapes. Most of the profiles show very broad Stokes I absorptions and complex and spatially variable Stokes V signatures. The inversion of the profiles shows evidence of different atmospheric blue- and redshifted components of the He I lines within the resolution element (1 arcsec), with supersonic velocities of up to 100 km/s. Up to five different atmospheric components are found in the same profile. We show that even these complex profiles can be reliably inverted.

  8. Rapid identification of Enterobacteriaceae with microbial enzyme activity profiles.

    Godsey, J H; Matteo, M R; Shen, D; Tolman, G; Gohlke, J R

    1981-01-01

    A total of 539 clinical isolates belonging to 10 species of the Enterobacteriaceae family were identified by enzyme activity profiles within 30 min of test inoculation. Each isolate was grown at 37 degrees C for 18 h on Mueller-Hinton agar and suspended to an optical density of 200 Klett units on 0.85% saline. Enzyme activity profiles were obtained by inoculating 18 fluorogenic substrates with the standardized bacterial suspension and monitoring initial rates of hydrolysis over the first 30 m...

  9. Cytokine profiles in asthma families depend on age and phenotype.

    Katrin Pukelsheim

    Full Text Available BACKGROUND: Circulating cytokine patterns may be relevant for the diagnosis of asthma, for the discrimination of certain phenotypes, and prognostic factors for exacerbation of disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated serum samples from 944 individuals of 218 asthma-affected families by a multiplex, microsphere based system detecting at high sensitivity eleven asthma associated mediators: eotaxin (CCL11, granulocyte macrophage stimulating factor (GM-CSF, interferon gamma (IFNγ, interleukin-4 (IL-4, IL-5, IL-8, IL-10, IL-12 (p40, IL-13, IL-17 and tumor necrosis factor alpha (TNFα. Single cytokine levels were largely similar between asthmatic and healthy individuals when analysing asthma as single disease entity. Regulatory differences between parental and pediatric asthma were reflected by six of the eleven mediators analyzed (eotaxin, IL-4, IL-5, IL-10, IL-12, TNFα. IL-12 (p40 and IL-5 were the best predictor for extrinsic asthma in children with an increased odds ratio of 2.85 and 1.96 per log pg/ml increase (IL-12 (p40: 1.2-6.8, p=0.019, and IL-5: 1.2-2.5, p=0.025. Frequent asthma attacks in children are associated with elevated IL-5 serum levels (p=0.013. Cytokine patterns seem to be individually balanced in both, healthy and diseased adults and children, with various cytokines correlating among each other (IL-17 and IFNγ (rs=0.67, IL-4 and IL-5 (rs=0.55, IFNγ and GM-CSF (rs=0.54. CONCLUSION/SIGNIFICANCE: Our data support mainly an age- but also an asthma phenotype-dependent systemic immune regulation.

  10. The comparison of two speed-dependent Voigt line profile models

    Protasevich, A. E.

    2013-07-01

    Numerical calculations of the ratio of line width and maximum value of two speed-dependent Voigt line profiles to the respective values of their speed-independent analogs are performed in the high-pressure limit. The intercomparison demonstrates considerable disagreement between different speed-dependent models.

  11. Semantic and Time-Dependent Expertise Profiling Models in Community-Driven Knowledge Curation Platforms

    Jane Hunter

    2013-10-01

    Full Text Available Online collaboration and web-based knowledge sharing have gained momentum as major components of the Web 2.0 movement. Consequently, knowledge embedded in such platforms is no longer static and continuously evolves through experts’ micro-contributions. Traditional Information Retrieval and Social Network Analysis techniques take a document-centric approach to expertise modeling by creating a macro-perspective of knowledge embedded in large corpus of static documents. However, as knowledge in collaboration platforms changes dynamically, the traditional macro-perspective is insufficient for tracking the evolution of knowledge and expertise. Hence, Expertise Profiling is presented with major challenges in the context of dynamic and evolving knowledge. In our previous study, we proposed a comprehensive, domain-independent model for expertise profiling in the context of evolving knowledge. In this paper, we incorporate Language Modeling into our methodology to enhance the accuracy of resulting profiles. Evaluation results indicate a significant improvement in the accuracy of profiles generated by this approach. In addition, we present our profile visualization tool, Profile Explorer, which serves as a paradigm for exploring and analyzing time-dependent expertise profiles in knowledge-bases where content evolves overtime. Profile Explorer facilitates comparative analysis of evolving expertise, independent of the domain and the methodology used in creating profiles.

  12. Cognitive profile and activities of daily living

    Borgwardt, Line Gutte; Thuesen, A M; Olsen, K J;

    2015-01-01

    BACKGROUND: Alpha-mannosidosis (OMIM 248500) (AM) is a rare lysosomal storage disease caused by a deficiency of the alpha-mannosidase enzyme. The typical signs consist of hearing impairment, intellectual disabilities, coarse facial features and motor function disturbances. We report on the...... cognitive function and activities of daily living in patients with AM. METHODS: Thirty five AM patients, age 6-35 years, were included in the study. As a cognitive function test, we used the Leiter international performance scale-revised (Leiter-R), which consists of two batteries: the visual function and...... assess that this group of patients has, despite their intellectual disabilities, a potential for continuous cognitive development, especially during childhood and early teenage years. This should be included and supported in the individual educational planning....

  13. Cholesterol-dependent hemolytic activity of Passiflora quadrangularis leaves

    L.N. Yuldasheva

    2005-07-01

    Full Text Available Plants used in traditional medicine are rich sources of hemolysins and cytolysins, which are potential bactericidal and anticancer drugs. The present study demonstrates for the first time the presence of a hemolysin in the leaves of Passiflora quadrangularis L. This hemolysin is heat stable, resistant to trypsin treatment, has the capacity to froth, and acts very rapidly. The hemolysin activity is dose-dependent, with a slope greater than 1 in a double-logarithmic plot. Polyethylene glycols of high molecular weight were able to reduce the rate of hemolysis, while liposomes containing cholesterol completely inhibited it. In contrast, liposomes containing phosphatidylcholine were ineffective. The Passiflora hemolysin markedly increased the conductance of planar lipid bilayers containing cholesterol but was ineffective in cholesterol-free bilayers. Successive extraction of the crude hemolysin with n-hexane, chloroform, ethyl acetate, and n-butanol resulted in a 10-fold purification, with the hemolytic activity being recovered in the n-butanol fraction. The data suggest that membrane cholesterol is the primary target for this hemolysin and that several hemolysin molecules form a large transmembrane water pore. The properties of the Passiflora hemolysin, such as its frothing ability, positive color reaction with vanillin, selective extraction with n-butanol, HPLC profile, cholesterol-dependent membrane susceptibility, formation of a stable complex with cholesterol, and rapid erythrocyte lysis kinetics indicate that it is probably a saponin.

  14. Probability of primordial black hole formation and its dependence on the radial profile of initial configurations

    In this paper we derive the probability of the radial profiles of spherically symmetric inhomogeneities in order to provide an improved estimation of the number density of primordial black holes (PBHs). We demonstrate that the probability of PBH formation depends sensitively on the radial profile of the initial configuration. We do this by characterizing this profile with two parameters chosen heuristically: the amplitude of the inhomogeneity and the second radial derivative, both evaluated at the center of the configuration. We calculate the joint probability of initial cosmological inhomogeneities as a function of these two parameters and then find a correspondence between these parameters and those used in numerical computations of PBH formation. Finally, we extend our heuristic study to evaluate the probability of PBH formation taking into account for the first time the radial profile of curvature inhomogeneities.

  15. Interpretation of the q-profile dependence of the LH power deposition profile during LHCD experiments on Tore Supra

    Identification of parameters and scenarios allowing to control accurately the Lower Hybrid (LH) power deposition profile remains nowadays one of the most challenging task in view to achieve steady-state advanced tokamak operation. The hard X-ray tomography system of Tore Supra is a powerful tool to carry out this type of studies, by allowing measurements of the LH power deposition profile at a level of accuracy which has never been reached so far on any tokamak. Recent observations by means of this diagnostic are reported, which bring evidence of the highly sensitive dependence of LH power deposition on the safety factor profile. The radial position of the wave absorption, which has been investigated both in transient (during plasma current ramp-up) and stationary (during Ip flat-top) regimes, during shots where the ohmic contribution to the total plasma current is dominant, shows a strong correlation with the value of Ip and the position of the q = 1 surface. Elements of interpretation of this behavior are found using ray-tracing and Fokker-Planck (RT/FP) simulations, carried out with a new ray-tracing program coupled to equilibrium reconstruction code IDENT-D. (authors)

  16. Profiles and Pauses: Two Practical Activities for the Writing Class

    Ernest Hall

    1998-01-01

    Full Text Available Abstract : This article describes two classroom activities, "Profiling" and "Pause Analysis", that can be successfully used in ESL writing classes. "Profiling" addresses such problems as poor development of ideas, simplistic ideas, and lack of coherence in written texts. "Pause Analysis" focusses on the thinking processes that students engage in while drafting text, processes such as searching for ideas, evaluat­ing ideas, and postponing ideas. Both activities enable the instructor to assume the role of intervener in the students' writing processes, rather than evaluator of the text produced. In drawing The attention of the student write to both product and process, "Profiling" and "Pause Analysis" help them develop an awareness of the relation-ship between ideas in English expository text and the thinking pro­cesses that writers engage in while drafting such text.

  17. Quantitative genetic activity graphical profiles for use in chemical evaluation

    Waters, M.D. [Environmental Protection Agency, Washington, DC (United States); Stack, H.F.; Garrett, N.E.; Jackson, M.A. [Environmental Health Research and Testing, Inc., Research Triangle Park, NC (United States)

    1990-12-31

    A graphic approach, terms a Genetic Activity Profile (GAP), was developed to display a matrix of data on the genetic and related effects of selected chemical agents. The profiles provide a visual overview of the quantitative (doses) and qualitative (test results) data for each chemical. Either the lowest effective dose or highest ineffective dose is recorded for each agent and bioassay. Up to 200 different test systems are represented across the GAP. Bioassay systems are organized according to the phylogeny of the test organisms and the end points of genetic activity. The methodology for producing and evaluating genetic activity profile was developed in collaboration with the International Agency for Research on Cancer (IARC). Data on individual chemicals were compiles by IARC and by the US Environmental Protection Agency (EPA). Data are available on 343 compounds selected from volumes 1-53 of the IARC Monographs and on 115 compounds identified as Superfund Priority Substances. Software to display the GAPs on an IBM-compatible personal computer is available from the authors. Structurally similar compounds frequently display qualitatively and quantitatively similar profiles of genetic activity. Through examination of the patterns of GAPs of pairs and groups of chemicals, it is possible to make more informed decisions regarding the selection of test batteries to be used in evaluation of chemical analogs. GAPs provided useful data for development of weight-of-evidence hazard ranking schemes. Also, some knowledge of the potential genetic activity of complex environmental mixtures may be gained from an assessment of the genetic activity profiles of component chemicals. The fundamental techniques and computer programs devised for the GAP database may be used to develop similar databases in other disciplines. 36 refs., 2 figs.

  18. Profiles for voltage-activated currents are multiphasic, not curvilinear

    Nissen, Per

    2016-01-01

    Data for voltage-activation of a potassium channel (Matulef et al. Proc Natl Acad Sci USA 110: 17886-17891. 2013) were, as conventionally done, fitted by the authors by a Boltzmann function, i.e. by a curvilinear profile. Reanalysis of the data reveals however that this interpretation must be rejected in favor of a multiphasic profile, a series of straight lines separated by discontinuous transitions, quite often in the form of noncontiguities (jumps). In contrast to the generally very poor fits to the Boltzmann profiles, the fits to multiphasic profiles are very good. (For the four replicates, the average deviations from the Boltzmann curves were 10- to 100-fold larger than the deviations from the multiphasic profiles.) The difference in the median values was statistically highly significant, P<0.001 in most cases. For the mean values the deviations from the Boltzmann curve were 20-fold larger than the deviations from the multiphasic profile, and the difference in the median values was also highly signifi...

  19. Activity-Based Protein Profiling of Rhomboid Proteases in Liposomes

    Wolf, E. V.; Seybold, M.; Hadravová, Romana; Stříšovský, Kvido; Verhelst, S. H. L.

    2015-01-01

    Roč. 16, č. 11 (2015), s. 1616-1621. ISSN 1439-4227 R&D Projects: GA MŠk(CZ) LK11206; GA MŠk LO1302 Institutional support: RVO:61388963 Keywords : activity -based protein profiling * chemical probes * inhibitors * intramembrane proteases * liposomes Subject RIV: CE - Biochemistry Impact factor: 3.088, year: 2014

  20. Antibiotic resistance profiles and quorum sensing-dependent virulence factors in clinical isolates of pseudomonas aeruginosa.

    Wang, Huafu; Tu, Faping; Gui, Zhihong; Lu, Xianghong; Chu, Weihua

    2013-06-01

    Pseudomonas aeruginosa produces multiple virulence factors that have been associated with quorum sensing. The aim of this study was to evaluate the prevalence of drug resistant profiles and quorum sensing related virulence factors. Pseudomonas aeruginosa were collected from different patients hospitalized in China, the isolates were tested for their susceptibility to different common antimicrobial drugs and detected QS-related virulence factors. We identified 170 isolates displaying impaired phenotypic activity, approximately 80 % of the isolates were found to exhibit the QS-dependent phenotypes, among them, 12 isolates were defective in AHLs production, and therefore considered QS-deficient strains. Resistance was most often observed to Cefazolin (81.2 %), followed by trimethoprim-sulfamethoxazole (73.5 %), ceftriaxone (62.4 %) and Cefotaxime, Levofloxacin, Ciprofloxacin (58.8 %), and to a lesser extent Meropenem (20.0 %), Cefepime (18.8 %), and Cefoperazone/sulbactam (2.4 %) The QS-deficient isolates that were negative for virulence factor production were generally less susceptible to the antimicrobials. The results showed a high incidences of antibiotic resistance and virulence properties in P. aeruginosa, and indicate that the clinical use of QS-inhibitory drugs that appear superior to conventional antimicrobials by not exerting any selective pressure on resistant strains. PMID:24426103

  1. Surface activity, lipid profiles and their implications in cervical cancer.

    Preetha A

    2005-01-01

    Full Text Available Background: The profiles of lipids in normal and cancerous tissues may differ revealing information about cancer development and progression. Lipids being surface active, changes in lipid profiles can manifest as altered surface activity profiles. Langmuir monolayers offer a convenient model for evaluating surface activity of biological membranes. Aims: The aims of this study were to quantify phospholipids and their effects on surface activity of normal and cancerous human cervical tissues as well as to evaluate the role of phosphatidylcholine (PC and sphingomyelin (SM in cervical cancer using Langmuir monolayers. Methods and Materials: Lipid quantification was done using thin layer chromatography and phosphorus assay. Surface activity was evaluated using Langmuir monolayers. Monolayers were formed on the surface of deionized water by spreading tissue organic phase corresponding to 1 mg of tissue and studying their surface pressure-area isotherms at body temperature. The PC and SM contents of cancerous human cervical tissues were higher than those of the normal human cervical tissues. Role of PC and SM were evaluated by adding varying amounts of these lipids to normal cervical pooled organic phase. Statistical analysis: Student′s t-test (p < 0.05 and one-way analysis of variance (ANOVA was used. Results: Our results reveals that the phosphatidylglycerol level in cancerous cervical tissue was nearly five folds higher than that in normal cervical tissue. Also PC and sphingomyelin SM were found to be the major phospholipid components in cancerous and normal cervical tissues respectively. The addition of either 1.5 µg DPPC or 0.5 µg SM /mg of tissue to the normal organic phase changed its surface activity profile to that of the cancerous tissues. Statistically significant surface activity parameters showed that PC and SM have remarkable roles in shifting the normal cervical lipophilic surface activity towards that of cancerous lipophilic

  2. Time-dependent modelling of 137Cs migration in Estonian soil profiles

    Our first countrywide study carried out in 1991-1993 determined both geographical and depth distributions of the deposited 134Cs and 137Cs in the Estonian soil. According to the results of this study and an independent air-borne scanning, radiocaesium originating from the 1986 Chernobyl accident with the mean deposition of 2 kBq m-2 was extremely unevenly distributed over the country . The mapped distribution is presented in Fig. 1. Our estimates demonstrated that about 2/3 of the total 137Cs inventory in Estonia was deposited in Ida-Virumaa County, NE Estonia, where the maximum depositions reached 40 kBq m-2. The region was revisited for soil sampling in 1998-2001. Undisturbed soil profiles down to a depth of ∼ 20 cm were collected and the 2-3 cm sample core slices analyzed using a low-background HPGe gamma spectrometer (42% efficiency and 1.7 keV resolution). As in the previous study, both total depositions and depth distributions of the deposited 134Cs (where possible) and 137Cs activity concentrations were determined. Depth distributions of the deposited activity showed considerable site-specific variations. In addition, it appeared that in comparison with our previous study, clear features of time-dependent migration to deeper soil layers were evident. The preliminary modeling has demonstrated that a lognormal distribution with varying parameters fits satisfactorily the determined depth-distributions of the Chernobyl radiocaesium activity concentration. An attempt was made to apply a single model to describe the observed time-dependent depth-distribution pattern over the time period of 1986-2001. We started from the multi-compartmental migration model for undisturbed soil (here Model RP72), presented in Fig. 2. This model has been elaborated basing on experimental migration results for Pu for a time period up to 30 y. For our application, the model is modified to account for the radioactive decay of 137Cs. The results of modeling using the original transfer

  3. Impurity profile tracking for active pharmaceutical ingredients: case reports.

    Zhou, Lili; Mao, Bing; Reamer, Robert; Novak, Tom; Ge, Zhihong

    2007-06-28

    Tracking the impurity profile of an active pharmaceutical ingredient (API) is a very important task for all stages of drug development. A systematic approach for tracking impurity profile of API is described. Various real pharmaceutical applications are presented through successful examples of impurity profile tracking for three different novel APIs. These include MK-0969, an M3 antagonist; MK-0677, an oral-active growth hormone secretagogue and API-A, a cathepsin K inhibitor. A general strategy including selection of a reversed phase high performance liquid chromatographic (RP-HPLC) impurity profile method based on screening various stationary phases and changing the pH of the mobile phase and elucidation of impurity structures through the utilization of LC-MS, preparative-LC and NMR is demonstrated. A series of studies were conducted on the peak purity check by using the LC-UV diode-array and LC-MS detections. The advantages and disadvantages of each technique in the evaluation of peak purity are discussed. PMID:17142001

  4. Psychological profile and nicotine dependence in smoking undergraduate students of UFMT

    Regina de Cássia Rondina

    2003-01-01

    Full Text Available INTRODUCTION: Data on the relationship between personality profile and nicotine dependence may help health professionals to design and improve programs for the treatment and prevention of this dependence. OBJECTIVE: To investigate the relationship between personality profile and nicotine dependence in a group of smoking undergraduate students. METHODS: A total of 1,245 undergraduate students were randomly selected among 10,500 students enrolled at the Cuiabá campus of UFMT in 2001. A standard questionnaire was applied for social characterization and for the determination of the tobacco consumption pattern, comprising 80 students considered as smokers. These students were then submitted to the Fagerström Test (1978 for nicotine dependence and to the reduced version of the Comrey Personality Scale (CPS, that determines personality dimensions. RESULTS: Analysis of the mean scores (Student's t test revealed an inversely proportional borderline association between dependence and the Order x Lack of Compulsion scale (p = 0.06, and a negative or inversely proportional association between the CPS Extroversion x Introversion (p = 0.002 and Control of Validity scales (p = 0.04. Linear regression analysis of the Fagerström Test points confirmed the inversely proportional borderline association between dependence and the Order x Lack of Compulsion (p = 0.06 and CPS Extroversion x Introversion scales (p = 0.02. However, when the interference of daily cigarette consumption was controlled, only the Extroversion x Introversion scale remained associated with dependence (p = 0.001. CONCLUSION: Students who are nicotine-dependent smokers are less extroverted than non-dependent smokers.

  5. Profile modification by light pressure in plasmas expanding with uniform, time-dependent temperature.

    Sanmartín Losada, Juan Ramón; Montañés García, José Luis

    1980-01-01

    Profile modification of laser plasmas, in the transition layer at critical density and in the flow on the overdense side, is studied. Assuming isothermal flow and low absorption within the layer, compression transitions are proved impossible and cavities possible only in subsonic flow. The overdense flow adjusts itself for a rarefaction transition in a manner (formation of plateaus, bumps, or cavities) critically dependent on how the (spatially uniform) temperature varies with time. Spherical...

  6. Heart rate and activity profile for young female soccer players

    Barbero Álvarez, José Carlos; Gómez López, Maite; Barbero Álvarez, Verónica; Granda Vera, Juan; Castagna, Carlo

    2008-01-01

    The physical and physiological demands of high-level male soccer have been studied extensively, while few studies have investigated the demands placed on females during match-play, however, there is no information available about the heart rate and activity profile of young female soccer players during match play. Therefore, the aim of this study was to examine cardiovascular (heart-rates HR) and physical demands of young female soccer players during a match. Players were observed during a fr...

  7. Hidden Markov Models for the Activity Profile of Terrorist Groups

    Raghavan, Vasanthan; Tartakovsky, Alexander G

    2012-01-01

    The main focus of this work is on developing models for the activity profile of a terrorist group, detecting sudden spurts and downfalls in this profile, and in general, tracking it over a period of time. Toward this goal, a d-state hidden Markov model (HMM) that captures the latent states underlying the dynamics of the group and thus its activity profile is developed. The simplest setting of d = 2 corresponds to the case where the dynamics are coarsely quantized as Active and Inactive, respectively. Two strategies for spurt detection and tracking are developed here: a model-independent strategy that uses the exponential weighted moving-average (EWMA) filter to track the strength of the group as measured by the number of attacks perpetrated by it, and a state estimation strategy that exploits the underlying HMM structure. The EWMA strategy is robust to modeling uncertainties and errors, and tracks persistent changes (changes that last for a sufficiently long duration) in the strength of the group. On the othe...

  8. Enzyme activity measurement via spectral evolution profiling and PARAFAC

    Baum, Andreas; Meyer, Anne S.; Garcia, Javier Lopez;

    2013-01-01

    The recent advances in multi-way analysis provide new solutions to traditional enzyme activity assessment. In the present study enzyme activity has been determined by monitoring spectral changes of substrates and products in real time. The method relies on measurement of distinct spectral...... fingerprints of the reaction mixture at specific time points during the course of the whole enzyme catalyzed reaction and employs multi-way analysis to detect the spectral changes. The methodology is demonstrated by spectral evolution profiling of Fourier Transform Infrared (FTIR) spectral fingerprints using...

  9. Age-dependence of relative telomere length profiles during spermatogenesis in man

    Jørgensen, Pernille Bach; Fedder, Jens; Koelvraa, Steen;

    2013-01-01

    Telomeres, the protective structures at the outmost ends of chromosomes, shorten in all somatic cells with each cell-division and by cumulative oxidative damage. To counteract that these shortened telomeres are passed on to offspring, the telomeres are elongated by the enzyme, telomerase, during...... human spermatogenesis. A few groups have tried to elucidate this process by measuring telomerase activity in the various cell-types during spermatogenesis, but until now, no one has ever measured telomere length (TL) during these different stages in humans. Some groups have measured TL in spermatozoa...... measured by telomere QFISH. Our data revealed no difference in the TL profile during spermatogenesis between younger and older men. All men had a similar profile which strongly resembled the telomerase expression profile found by others. This indicates that the longer telomeres in older men are not caused...

  10. Phenotype microarray profiling of the antibacterial activity of red cabbage

    Hafidh RR

    2012-06-01

    Full Text Available Background: Functional food can be a potent source of wide array of biocomonents with antimicrobial activity. We investigated the antibacterial activity of red cabbage (RC extract on Gram negative and positive ATCC strains. Most intersting, we, for the first time, explored and analysed the complete phenotypic profile of RC-treated bacteria using Omnilog Phenotype Microarray. Results: This study revealed that the phenotype microarray (PM screen was a valuable tool in the search for compounds and their antibacterial mechanisms that can inhibit bacterial growth by affecting certain metabolic pathways. It was shown that RC exerted remarkable antibacterial effect on S. aureus and E. coli bacteria, and PM showed a wide range phenotypic profile of the exerted RC antibacterial activity. RC targeted the peptide, carbon, nutriontional assembly, and sulfur metbolic pathways altogether. The peptidoglycan synthesis pathway was inferred to be targeted by RC extract at a metabolic point different from other available cell wall-targeting drugs; these could be hot targets for the discovery of new therapy for many problematic microbes.Conclusions: Taken together, the phenotype microarray for functional food and medicinal plants can be a very useful tool for profiling their antimicrobial activity. Moreover, extracts of functional food can exert antibacterial activity by hitting a wide range of metabolic pathways, at the same time leading to very difficult condition for bacteria to rapidly develop resistance. Therefore, using functional foods or medicinal plants as such, or as extracts, can be superior on mono-targeting antibiotics if the optimal concentrations and conditions of these functional foods were sought.

  11. Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines

    James Campbell

    2016-03-01

    Full Text Available One approach to identifying cancer-specific vulnerabilities and therapeutic targets is to profile genetic dependencies in cancer cell lines. Here, we describe data from a series of siRNA screens that identify the kinase genetic dependencies in 117 cancer cell lines from ten cancer types. By integrating the siRNA screen data with molecular profiling data, including exome sequencing data, we show how vulnerabilities/genetic dependencies that are associated with mutations in specific cancer driver genes can be identified. By integrating additional data sets into this analysis, including protein-protein interaction data, we also demonstrate that the genetic dependencies associated with many cancer driver genes form dense connections on functional interaction networks. We demonstrate the utility of this resource by using it to predict the drug sensitivity of genetically or histologically defined subsets of tumor cell lines, including an increased sensitivity of osteosarcoma cell lines to FGFR inhibitors and SMAD4 mutant tumor cells to mitotic inhibitors.

  12. Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines

    Campbell, James; Ryan, Colm J.; Brough, Rachel; Bajrami, Ilirjana; Pemberton, Helen N.; Chong, Irene Y.; Costa-Cabral, Sara; Frankum, Jessica; Gulati, Aditi; Holme, Harriet; Miller, Rowan; Postel-Vinay, Sophie; Rafiq, Rumana; Wei, Wenbin; Williamson, Chris T.; Quigley, David A.; Tym, Joe; Al-Lazikani, Bissan; Fenton, Timothy; Natrajan, Rachael; Strauss, Sandra J.; Ashworth, Alan; Lord, Christopher J.

    2016-01-01

    Summary One approach to identifying cancer-specific vulnerabilities and therapeutic targets is to profile genetic dependencies in cancer cell lines. Here, we describe data from a series of siRNA screens that identify the kinase genetic dependencies in 117 cancer cell lines from ten cancer types. By integrating the siRNA screen data with molecular profiling data, including exome sequencing data, we show how vulnerabilities/genetic dependencies that are associated with mutations in specific cancer driver genes can be identified. By integrating additional data sets into this analysis, including protein-protein interaction data, we also demonstrate that the genetic dependencies associated with many cancer driver genes form dense connections on functional interaction networks. We demonstrate the utility of this resource by using it to predict the drug sensitivity of genetically or histologically defined subsets of tumor cell lines, including an increased sensitivity of osteosarcoma cell lines to FGFR inhibitors and SMAD4 mutant tumor cells to mitotic inhibitors. PMID:26947069

  13. Ribosome-dependent activation of stringent control.

    Brown, Alan; Fernández, Israel S; Gordiyenko, Yuliya; Ramakrishnan, V

    2016-06-01

    In order to survive, bacteria continually sense, and respond to, environmental fluctuations. Stringent control represents a key bacterial stress response to nutrient starvation that leads to rapid and comprehensive reprogramming of metabolic and transcriptional patterns. In general, transcription of genes for growth and proliferation is downregulated, while those important for survival and virulence are upregulated. Amino acid starvation is sensed by depletion of the aminoacylated tRNA pools, and this results in accumulation of ribosomes stalled with non-aminoacylated (uncharged) tRNA in the ribosomal A site. RelA is recruited to stalled ribosomes and activated to synthesize a hyperphosphorylated guanosine analogue, (p)ppGpp, which acts as a pleiotropic secondary messenger. However, structural information about how RelA recognizes stalled ribosomes and discriminates against aminoacylated tRNAs is missing. Here we present the cryo-electron microscopy structure of RelA bound to the bacterial ribosome stalled with uncharged tRNA. The structure reveals that RelA utilizes a distinct binding site compared to the translational factors, with a multi-domain architecture that wraps around a highly distorted A-site tRNA. The TGS (ThrRS, GTPase and SpoT) domain of RelA binds the CCA tail to orient the free 3' hydroxyl group of the terminal adenosine towards a β-strand, such that an aminoacylated tRNA at this position would be sterically precluded. The structure supports a model in which association of RelA with the ribosome suppresses auto-inhibition to activate synthesis of (p)ppGpp and initiate the stringent response. Since stringent control is responsible for the survival of pathogenic bacteria under stress conditions, and contributes to chronic infections and antibiotic tolerance, RelA represents a good target for the development of novel antibacterial therapeutics. PMID:27279228

  14. Universal Temporal Profile of Replication Origin Activation in Eukaryotes

    Goldar, Arach

    2011-03-01

    The complete and faithful transmission of eukaryotic genome to daughter cells involves the timely duplication of mother cell's DNA. DNA replication starts at multiple chromosomal positions called replication origin. From each activated replication origin two replication forks progress in opposite direction and duplicate the mother cell's DNA. While it is widely accepted that in eukaryotic organisms replication origins are activated in a stochastic manner, little is known on the sources of the observed stochasticity. It is often associated to the population variability to enter S phase. We extract from a growing Saccharomyces cerevisiae population the average rate of origin activation in a single cell by combining single molecule measurements and a numerical deconvolution technique. We show that the temporal profile of the rate of origin activation in a single cell is similar to the one extracted from a replicating cell population. Taking into account this observation we exclude the population variability as the origin of observed stochasticity in origin activation. We confirm that the rate of origin activation increases in the early stage of S phase and decreases at the latter stage. The population average activation rate extracted from single molecule analysis is in prefect accordance with the activation rate extracted from published micro-array data, confirming therefore the homogeneity and genome scale invariance of dynamic of replication process. All these observations point toward a possible role of replication fork to control the rate of origin activation.

  15. Power Dependence of the Electron Mobility Profile in a Hall Thruster

    Jorns, Benjamin A.; Hofery, Richard H.; Mikellides, Ioannis G.

    2014-01-01

    The electron mobility profile is estimated in a 4.5 kW commercial Hall thruster as a function of discharge power. Internal measurements of plasma potential and electron temperature are made in the thruster channel with a high-speed translating probe. These measurements are presented for a range of throttling conditions from 150 - 400 V and 0.6 - 4.5 kW. The fluid-based solver, Hall2De, is used in conjunction with these internal plasma parameters to estimate the anomalous collision frequency profile at fixed voltage, 300 V, and three power levels. It is found that the anomalous collision frequency profile does not change significantly upstream of the location of the magnetic field peak but that the extent and magnitude of the anomalous collision frequency downstream of the magnetic peak does change with thruster power. These results are discussed in the context of developing phenomenological models for how the collision frequency profile depends on thruster operating conditions.

  16. Size Dependent Antioxidant Activity of Polypyrrole Nanofibers

    Kumar, A.; Banerjee, Somik

    2011-07-01

    Polypyrrole (PPy) nanofibers have been synthesized employing surfactant assisted miceller polymerization by varying the surfactant concentration. The synthesized nanofibers have been characterized using TEM, XRD, FTIR and UV-Visible spectroscopy. TEM reveals that the diameter of the PPy nanowires decreases with the increase in surfactant concentration. X-ray spectra shows an amorphous peak centered around 2θ = 24.6° which is attributed to the π-π interaction of the partial PPy chains similar to that of aromatic groups. The domain length of the samples determined using the single-line approximation technique, decreases with decreasing diameter whereas the strain in the material increases, which have been attributed to the reduction of size with increase in the surfactant concentration as revealed by TEM. The vibrational bands observed from the FTIR spectra confirm the formation of surfactant free PPy nanowires. UV-Visible spectra shows a blue-shift in the π-π* absorption peak. Antioxidant activity of the samples has been determined using the DPPH free radical method. It has been observed that enhancement in free radical scavenging coincides with the decreasing diameter of the PPy nanofibers which has been associated with the increase in the surface reaction sites with the reduction of size.

  17. Differential migration and activation profile of monocytes after trophoblast interaction.

    Esteban Grasso

    Full Text Available Macrophages at the maternal-placental interface coordinate opposite demands under the control of trophoblast cells such as the response against pathogens on one hand, and apoptotic cell clearance and wound healing with the production of suppressor cytokines. Here, we investigated whether trophoblast cells induce maternal monocyte activation towards an alternative activated macrophage profile and whether bacterial or viral stimuli modulate their migratory properties. We used an in vitro model of the maternal-placental interface represented by co-cultures of CD14+ cells isolated from fertile women with first trimester trophoblast cell line (Swan-71 cells in the presence or absence of pathogen associated molecular pattern (PAMP stimuli lipopolysaccharide (LPS, peptidoglycan (PGN or poly [I:C]. Maternal CD14+ cells showed increased CD16 and CD39 expression, both markers associated to an alternative activation profile, with no changes in CD80 expression after trophoblast cell interaction. These changes were accompanied by increased IL-10 and decreased IL-12 production by CD14+ cells. After stimulation with LPS, PGN or poly [I:C], monocytes co-cultured with trophoblast cells had lower production of TNF-α and IL-1β compared with non co-cultured monocytes. Interestingly, monocyte migration towards trophoblast cells was prevented in the presence of LPS or PGN but not after 24h of stimulation with poly [I:C]. LPS or PGN also decreased CCR5, CXCL-8 and CCL5 expression. Finally, trophoblast cells co-cultured with monocytes in the presence of pathological stimuli failed to increase chemokine expression, indicating a bidirectional effect. In conclusion, trophoblast might 'instruct' maternal monocytes to express an alternative activation profile and restrain their early recruitment under pathological threats as one of the first strategies to avoid potential tissue damage at the maternal-placental interface.

  18. Nicotine dependence, physical activity, and sedentary behavior among adult smokers

    Paul D Loprinzi

    2015-01-01

    Full Text Available Background: Research has previously demonstrated an inverse association between smoking status and physical activity; however, few studies have examined the association between nicotine dependence and physical activity or sedentary behavior. Aim: This study examined the association between nicotine dependence and accelerometer-determined physical activity and sedentary behavior. Materials and Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES were used. A total of 851 adult (≥20 years smokers wore an accelerometer for ≥4 days and completed the Fagerstrom Test for Nicotine Dependence scale. Regression models were used to examine the association between nicotine dependence and physical activity/sedentary behavior. Results: After adjusting for age, gender, race-ethnicity, poverty level, hypertension, emphysema, bronchitis, body mass index (BMI, cotinine, and accelerometer wear time, smokers 50 + years of age with greater nicotine dependence engaged in more sedentary behavior (β = 11.4, P = 0.02 and less light-intensity physical activity (β = −9.6, P = 0.03 and moderate-to-vigorous physical activity (MVPA; β = −0.14, P = 0.003 than their less nicotine dependent counterparts. Conclusion: Older adults who are more nicotine dependent engage in less physical activity (both MVPA and light-intensity and more sedentary behavior than their less nicotine dependent counterparts.

  19. Evaluation of Kinase Activity Profiling Using Chemical Proteomics.

    Ruprecht, Benjamin; Zecha, Jana; Heinzlmeir, Stephanie; Médard, Guillaume; Lemeer, Simone; Kuster, Bernhard

    2015-12-18

    Protein kinases are important mediators of intracellular signaling and are reversibly activated by phosphorylation. Immobilized kinase inhibitors can be used to enrich these often low-abundance proteins, to identify targets of kinase inhibitors, or to probe their selectivity. It has been suggested that the binding of kinases to affinity beads reflects a kinase's activation status, a concept that is under considerable debate. To assess the merits of the idea, we performed a series of experiments including quantitative phosphoproteomics and purification of kinases by single or mixed affinity matrices from signaling activated or resting cancer cells. The data show that mixed affinity beads largely bind kinases independent of their activation status, and experiments using individual immobilized kinase inhibitors show mixed results in terms of preference for binding the active or inactive conformation. Taken together, activity- or conformation-dependent binding to such affinity resins depends (i) on the kinase, (ii) on the affinity probe, and (iii) on the activation status of the lysate or cell. As a result, great caution should be exercised when inferring kinase activity from such binding data. The results also suggest that assaying kinase activity using binding data is restricted to a limited number of well-chosen cases. PMID:26378887

  20. Dynamic Statistical Profiling of Communication Activity in Distributed Applications

    Vetter, J

    2001-10-12

    A complete trace of communication activity for a terascale application is overwhelming in terms of overhead and storage. We propose a novel alternative that enables profiling of the application's communication activity using statistical message sampling during runtime. We have implemented an operational prototype and our evidence shows that this new technique can provide an accurate, low-overhead, tractable alternative for performance analysis of communication activity. Moreover, this alternative enables an assortment of runtime analysis techniques not previously available with post-mortem, trace-based systems. Our assessment of relative performance and coverage of different sampling and analysis methods shows that purely random selection is preferred over counter- and timer-based sampling. Experiments on several applications running up to 128 processors demonstrate the viability of this approach. In particular, on one application, statistical profiling results contradict conclusions based on evidence from tracing. The design of our prototype reveals that parsimonious modifications to the MPI runtime system could facilitate such techniques on production computing systems, and it suggests that this sampling technique could execute continuously for long-running applications.

  1. Chemoproteomic profiling of host and pathogen enzymes active in cholera.

    Hatzios, Stavroula K; Abel, Sören; Martell, Julianne; Hubbard, Troy; Sasabe, Jumpei; Munera, Diana; Clark, Lars; Bachovchin, Daniel A; Qadri, Firdausi; Ryan, Edward T; Davis, Brigid M; Weerapana, Eranthie; Waldor, Matthew K

    2016-04-01

    Activity-based protein profiling (ABPP) is a chemoproteomic tool for detecting active enzymes in complex biological systems. We used ABPP to identify secreted bacterial and host serine hydrolases that are active in animals infected with the cholera pathogen Vibrio cholerae. Four V. cholerae proteases were consistently active in infected rabbits, and one, VC0157 (renamed IvaP), was also active in human choleric stool. Inactivation of IvaP influenced the activity of other secreted V. cholerae and rabbit enzymes in vivo, and genetic disruption of all four proteases increased the abundance of intelectin, an intestinal lectin, and its binding to V. cholerae in infected rabbits. Intelectin also bound to other enteric bacterial pathogens, suggesting that it may constitute a previously unrecognized mechanism of bacterial surveillance in the intestine that is inhibited by pathogen-secreted proteases. Our work demonstrates the power of activity-based proteomics to reveal host-pathogen enzymatic dialog in an animal model of infection. PMID:26900865

  2. Plasma renin activity profile in normal and hypertensive Filipinos

    To establish a base line profile of plasma renin activity in normotensive and hypertensive Filipinos, 1.019 cases, 479 males and 540 females with an age range 14 - 89 years (mean - 46 +-20) were studied at the Santo Tomas University Hospital of various life styles from the Metro-Manila area, 248 comprised the normotensive group (male - 122 or 49.2 %, female 126 or 50.8 %) and 771 were hypertensive. Of these, 711 (92.6 %) has essential hypertension and are presented in this report. Plasma Renin Activity was determined by radioimmunoassay using Dainabot Renin-Ricket. Concurrent 24 hr. urine sodium and potassium were determined. Nomograms of plasma renin activity as related to urine sodium excretion were drawn after computerized statistical analysis of data. The normal mean value of plasma renin activity was found to be 1.64 +- 0.81 ng./ml./hr. in the upright position and 1.15 +- .68 ng./ml./hr. in the supine position. Based on the nomogram derived, the values obtained in the 711 cases of essential hypertension were classified into High Renin - 14.3 % Normal Renin - 56.1 % and Low Renin - 29.6 %. This study establishes normal levels of plasma renin activity as well as define and classify same renin activity among hypertensive Filipinos, a useful and practicable guide for treatment and can be of prognostic significance. (author)

  3. Physicochemical signatures of nanoparticle-dependent complement activation

    Thomas, Dennis G.; Chikkagoudar, Satish; Heredia-Langner, Alejandro; Tardiff, Mark F.; Xu, Zhixiang; Hourcade, Dennis E.; Pham, Christine T. N.; Lanza, Gregory M.; Weinberger, Kilian Q.; Baker, Nathan A.

    2014-01-01

    Nanoparticles are potentially powerful therapeutic tools that have the capacity to target drug payloads and imaging agents. However, some nanoparticles can activate complement, a branch of the innate immune system, and cause adverse side-effects. Recently, we employed an in vitro hemolysis assay to measure the serum complement activity of perfluorocarbon nanoparticles that differed by size, surface charge, and surface chemistry, quantifying the nanoparticle-dependent complement activity using a metric called Residual Hemolytic Activity (RHA). In the present work, we have used a decision tree learning algorithm to derive the rules for estimating nanoparticle-dependent complement response based on the data generated from the hemolytic assay studies. Our results indicate that physicochemical properties of nanoparticles, namely, size, polydispersity index, zeta potential, and mole percentage of the active surface ligand of a nanoparticle, can serve as good descriptors for prediction of nanoparticle-dependent complement activation in the decision tree modeling framework.

  4. Physicochemical signatures of nanoparticle-dependent complement activation

    Nanoparticles are potentially powerful therapeutic tools that have the capacity to target drug payloads and imaging agents. However, some nanoparticles can activate complement, a branch of the innate immune system, and cause adverse side-effects. Recently, we employed an in vitro hemolysis assay to measure the serum complement activity of perfluorocarbon nanoparticles that differed by size, surface charge, and surface chemistry, quantifying the nanoparticle-dependent complement activity using a metric called Residual Hemolytic Activity (RHA). In the present work, we have used a decision tree learning algorithm to derive the rules for estimating nanoparticle-dependent complement response based on the data generated from the hemolytic assay studies. Our results indicate that physicochemical properties of nanoparticles, namely, size, polydispersity index, zeta potential, and mole percentage of the active surface ligand of a nanoparticle, can serve as good descriptors for prediction of nanoparticle-dependent complement activation in the decision tree modeling framework. (papers)

  5. Optimality of a time-dependent treatment profile during an epidemic.

    Jaberi-Douraki, Majid; Moghadas, Seyed M

    2013-01-01

    The emergence and spread of drug resistance is one of the most challenging public health issues in the treatment of some infectious diseases. The objective of this work is to investigate whether the effect of resistance can be contained through a time-dependent treatment strategy during the epidemic subject to an isoperimetric constraint. We apply control theory to a population dynamical model of influenza infection with drug-sensitive and drug-resistant strains, and solve the associated control problem to find the optimal treatment profile that minimizes the cumulative number of infections (i.e. the epidemic final size). We consider the problem under the assumption of limited drug stockpile and show that as the size of stockpile increases, a longer delay in start of treatment is required to minimize the total number of infections. Our findings show that the amount of drugs used to minimize the total number of infections depends on the rate of de novo resistance regardless of the initial size of drug stockpile. We demonstrate that both the rate of resistance emergence and the relative transmissibility of the resistant strain play important roles in determining the optimal timing and level of treatment profile. PMID:23859002

  6. Activity-dependent modulation of neural circuit synaptic connectivity

    Tessier, Charles R.; Kendal Broadie

    2009-01-01

    In many nervous systems, the establishment of neural circuits is known to proceed via a two-stage process; 1) early, activity-independent wiring to produce a rough map characterized by excessive synaptic connections, and 2) subsequent, use-dependent pruning to eliminate inappropriate connections and reinforce maintained synapses. In invertebrates, however, evidence of the activity-dependent phase of synaptic refinement has been elusive, and the dogma has long been that invertebrate circ...

  7. Linear Energy Transfer-Dependent Change in Rice Gene Expression Profile after Heavy-Ion Beam Irradiation

    Ishii, Kotaro; Kazama, Yusuke; Morita, Ryouhei; Hirano, Tomonari; Ikeda, Tokihiro; Usuda, Sachiko; Hayashi, Yoriko; Ohbu, Sumie; Motoyama, Ritsuko; Nagamura, Yoshiaki; Abe, Tomoko

    2016-01-01

    A heavy-ion beam has been recognized as an effective mutagen for plant breeding and applied to the many kinds of crops including rice. In contrast with X-ray or γ-ray, the heavy-ion beam is characterized by a high linear energy transfer (LET). LET is an important factor affecting several aspects of the irradiation effect, e.g. cell survival and mutation frequency, making the heavy-ion beam an effective mutagen. To study the mechanisms behind LET-dependent effects, expression profiling was performed after heavy-ion beam irradiation of imbibed rice seeds. Array-based experiments at three time points (0.5, 1, 2 h after the irradiation) revealed that the number of up- or down-regulated genes was highest 2 h after irradiation. Array-based experiments with four different LETs at 2 h after irradiation identified LET-independent regulated genes that were up/down-regulated regardless of the value of LET; LET–dependent regulated genes, whose expression level increased with the rise of LET value, were also identified. Gene ontology (GO) analysis of LET-independent up-regulated genes showed that some GO terms were commonly enriched, both 2 hours and 3 weeks after irradiation. GO terms enriched in LET-dependent regulated genes implied that some factor regulates genes that have kinase activity or DNA-binding activity in cooperation with the ATM gene. Of the LET-dependent up-regulated genes, OsPARP3 and OsPCNA were identified, which are involved in DNA repair pathways. This indicates that the Ku-independent alternative non-homologous end-joining pathway may contribute to repairing complex DNA legions induced by high-LET irradiation. These findings may clarify various LET-dependent responses in rice. PMID:27462908

  8. Molecular profiling of activated neurons by phosphorylated ribosome capture.

    Knight, Zachary A; Tan, Keith; Birsoy, Kivanc; Schmidt, Sarah; Garrison, Jennifer L; Wysocki, Robert W; Emiliano, Ana; Ekstrand, Mats I; Friedman, Jeffrey M

    2012-11-21

    The mammalian brain is composed of thousands of interacting neural cell types. Systematic approaches to establish the molecular identity of functional populations of neurons would advance our understanding of neural mechanisms controlling behavior. Here, we show that ribosomal protein S6, a structural component of the ribosome, becomes phosphorylated in neurons activated by a wide range of stimuli. We show that these phosphorylated ribosomes can be captured from mouse brain homogenates, thereby enriching directly for the mRNAs expressed in discrete subpopulations of activated cells. We use this approach to identify neurons in the hypothalamus regulated by changes in salt balance or food availability. We show that galanin neurons are activated by fasting and that prodynorphin neurons restrain food intake during scheduled feeding. These studies identify elements of the neural circuit that controls food intake and illustrate how the activity-dependent capture of cell-type-specific transcripts can elucidate the functional organization of a complex tissue. PMID:23178128

  9. AGE-DEPENDENT CHANGES IN ACTIVITY OF MALLARD PLASMA CHOLINESTERASES

    Plasma acetylcholinesterase (AChE) and butrylcholinesterase (BChE) activity was measured repeatedly in 27 mallard (Anas platyrhynchos) ducklings between 7 and 85 days of age to determine age-dependent changes in enzyme activity. Plasma AChE, BChe, and total cholinesterase (ChE) a...

  10. Flavonoid profile and antileukemic activity of Coreopsis lanceolata flowers.

    Pardede, Antoni; Mashita, Koharu; Ninomiya, Masayuki; Tanaka, Kaori; Koketsu, Mamoru

    2016-06-15

    Coreopsis lanceolata is a perennial plant belonging to the Asteraceae family. In this study, flavonoid profile and antileukemic potential of yellow flowers of the plant were investigated. The total flavonoid content in EtOAc fraction of the flower methanol extract was found to be 420mg/g and showed the inhibition of cell proliferation and possible induction of apoptosis in human leukemia HL-60 cells. Our phytochemical research led to the isolation of rare flavonoids including a flavanone, chalcones, and aurones; in particular, 4-methoxylanceoletin demonstrated the potent antiproliferative activity. Comparison with other Asteraceaeous flowers by UPLC-MS analysis indicated that the isolates are characteristic constituents of C. lanceolata. PMID:27155901

  11. Tea and herbal infusions: Their antioxidant activity and phenolic profile

    Tea and herbal infusions have been studied for their polyphenolic content, antioxidant activity and phenolic profile. The total phenolics recovered by ethyl acetate from the water extract, were determined by the Folin-Ciocalteu procedure and ranged from 88.1 ± 0.42 (Greek mountain tea) to 1216 ± 32.0 mg (Chinese green tea) GAE (Gallic acid equivalents)/cup. The antioxidant activity was evaluated by two methods, DPPH and chemiluminescence assays, using Trolox and quercetin as standards. The EC50 of herbal extracts ranged from 0.151 ± 0.002 mg extract/mg DPPH (0.38 quercetin equivalents and 0.57 Trolox equivalents), for Chinese green tea, to 0.77 ± 0.012 mg extract/mg DPPH (0.08 quercetin equivalents and 0.13 Trolox equivalents), for Greek mountain tea. Chemiluminescence assay results showed that the IC50 ranged from 0.17 ± 3.4 x 103 lg extract/ml of the final solution in the measuring cell (1.89 quercetin and 5.89 Trolox equivalents) for Chinese green tea, to 1.10 ± 1.86 x 102 g extract/ml of the final solution in the measuring cell (0.29 quercetin and 0.90 Trolox equivalents) for Greek mountain tea. The phenolic profile in the herbal infusions was investigated by LC-DAD-MS in the positive electrospray ionization (ESI) mode. About 60 different flavo- noids, phenolic acids and their derivatives have been identified. (author)

  12. Wavelength dependent near-range lidar profiling of smog aerosol over Athens

    Stachlewska, Iwona S.; Marinou, Eleni; Engelmann, Ronny; Costa Surós, Montserrat; Kottas, Mickael; Baars, Holger; Janicka, Lucja; Solomos, Stavros; Heese, Birgit; Kumala, Wojciech; Tsekeri, Alexandra; Binietoglou, Ioannis; Markowicz, Krzysztof M.; Amiridis, Vassilis; Balis, Dimitris; Althausen, Dietrich; Wandinger, Ulla; Ansmann, Albert

    2016-04-01

    Recently, the ACTRIS2 JRA1 field campaign focusing on joint remote and in-situ sensing of absorbing aerosols has been conducted in Athens (http://actris-athens.eu). In the frame of the ACTRIS2 BL-Smog TNA, co-located measurements of the near-range lidar receiver (NARLa) of the University of Warsaw with the multi-wavelength PollyXT lidar of the National Observatory of Athens were performed. The excellent capacities of the PollyXT-NOA lidar, equipped with eight far-range channels (355, 355s, 387, 407, 532, 532s, 607, and 1064nm) and two near-range channels (532 and 607 nm), were enhanced by integrating the NARLa for simultaneous observations. By using the NARLa, equipped with the elastic channels (355 and 532nm) and Raman channels (387 and 607nm), the wavelength dependence of the aerosol particles properties within boundary layer was captured. The dominant conditions observed during the JRA1 period were the fresh winter smog layers occurring in lowermost boundary layer over Athens. NARLa provided profiles as close to surface as 50m, thus the data obtained in the near-range were used for the incomplete overlap region of the far-field channels. With NARLa we assessed the overlap at 355 and 532nm wavelengths and concluded on the possibility of using the single near-range 532 nm channel for the overlap correction in both VIS and UV channels of the PollyXT-NOA. As a result, the obtained lidar profiles are expected to be more consistent with the sunphotometer measurements. In the future, the GARRLiC code can be applied on the synergy of combined near and far range lidar profiles with AERONET data sets in order to study improvement on the inversion results.

  13. Activity-dependent neuronal signalling and autism spectrum disorder

    Ebert, Daniel H.; Greenberg, Michael E.

    2013-01-01

    Neuronal activity induces the post-translational modification of synaptic molecules, promotes localized protein synthesis within dendrites and activates gene transcription, thereby regulating synaptic function and allowing neuronal circuits to respond dynamically to experience. Evidence indicates that many of the genes that are mutated in autism spectrum disorders are crucial components of the activity-dependent signalling networks that regulate synapse development and plasticity. Dysregulati...

  14. Profile of deferasirox for the treatment of patients with non-transfusion-dependent thalassemia syndromes

    Ricchi, Paolo; Marsella, Maria

    2015-01-01

    It has been clearly shown that iron overload adds progressively significant morbidity and mortality in patients with non-transfusion-dependent thalassemia (NTDT). The lack of physiological mechanisms to eliminate the excess of iron requires effective iron chelation therapy. The reduced compliance to deferoxamine and the risk of severe hematological adverse events during deferiprone treatment have limited the use of both these drugs to correct iron imbalance in NTDT. According to the principles of evidence-based medicine, following the demonstration of the effectiveness and the safety of deferasirox (Exjade®) in a prospective, randomized, controlled trial, deferasirox was approved by the US Food and Drug Administration in May 2013 for the treatment of iron overload associated with NTDT. This review, assessing the available scientific literature, will focus on the profile of DFX in the treatment of non-transfusional hemosiderosis in patients with NTDT. PMID:26719673

  15. Efficacy of treatment in an opioid -dependent population group using the Maudsley Addiction Profile (MAP) tool.

    Collins, Ruth; Boggs, Bob; Taggart, Noel; Kelly, Martin; Drillington, Aileen; Swanton, Ivy; Patterson, Diane

    2009-01-01

    A pilot study was performed to assess the effectiveness of treatment in an opioid dependent population using the Maudsley Addiction Profile (MAP) tool1.The primary outcome of the study was to assess if treatment had an effect on 1. Substance use (quantity and frequency of use), 2. Health risk behaviour (injecting and sharing injecting equipment), 3. Health symptoms (physical and psychological) and 4. Personal /Social functioning (relationships, employment and crime). A secondary outcome was also sought.The study took place in 2007 in an inner city Belfast hospital specialising in the treatment of addiction, over a two month period. Fifteen patients, all opioid dependent and receiving outpatient community treatment, were interviewed at baseline (prior to the commencement of treatment) and at eight weeks follow up.Three patients were lost to follow up. Two patients stopped using altogether. Of the remaining patients, improvements were seen in most areas. There was a decrease in the use of heroin (71.28%), cocaine (99.72%), crack cocaine (100%), cannabis (99.94%) and alcohol (33.17%). There was a reduction in injecting behaviour (60.93%). Improvements were observed in health with a reduction in physical (41.35%) and psychological (35%) symptoms. Overall personal and social functioning improved regarding interactions with family and friends. A reduction in crime was also observed (75%).Opinions and views of staff involved in the study were generally positive.This patient population presents with multiple and complex needs. Effective treatment needs to address these needs and not just drug addiction alone. The Maudsley Addiction Profile tool highlights this. PMID:19252726

  16. Novel TPP-riboswitch activators bypass metabolic enzyme dependency

    Mayer, Günter; Lünse, Christina; Suckling, Colin; Scott, Fraser

    2014-07-01

    Riboswitches are conserved regions within mRNA molecules that bind specific metabolites and regulate gene expression. TPP-riboswitches, which respond to thiamine pyrophosphate (TPP), are involved in the regulation of thiamine metabolism in numerous bacteria. As these regulatory RNAs are often modulating essential biosynthesis pathways they have become increasingly interesting as promising antibacterial targets. Here, we describe thiamine analogs containing a central 1,2,3-triazole group to induce repression of thiM-riboswitch dependent gene expression in different E. coli strains. Additionally, we show that compound activation is dependent on proteins involved in the metabolic pathways of thiamine uptake and synthesis. The most promising molecule, triazolethiamine (TT), shows concentration dependent reporter gene repression that is dependent on the presence of thiamine kinase ThiK, whereas the effect of pyrithiamine (PT), a known TPP-riboswitch modulator, is ThiK independent. We further show that this dependence can be bypassed by triazolethiamine-derivatives that bear phosphate-mimicking moieties. As triazolethiamine reveals superior activity compared to pyrithiamine, it represents a very promising starting point for developing novel antibacterial compounds that target TPP-riboswitches. Riboswitch-targeting compounds engage diverse endogenous mechanisms to attain in vivo activity. These findings are of importance for the understanding of compounds that require metabolic activation to achieve effective riboswitch modulation and they enable the design of novel compound generations that are independent of endogenous activation mechanisms.

  17. Chemical profiling of Centella asiatica under different extraction solvents and its antibacterial activity, antioxidant activity

    Supawan Rattanakom; Patchanee Yasurin

    2015-01-01

    Centella asiatica (L) urban, synonym Hydrocotyle asiatica, is found almost all over the world. This plant is famous in Ayurvedic medicine and used in the management of central nervous system, skin and gastrointestinal disorder. Thus this research had been done to evaluate the effect of solvent extraction (Ethanol, Chloroform and Hexane) of C. asiatica on chemical profile, antioxidant activity and antibacterial activity against some foodborne pathogens. The result showed that all solvents (et...

  18. Profiling of REST-dependent microRNAs reveals dynamic modes of expression

    Zhengliang eGao

    2012-05-01

    Full Text Available Multipotent neural stem cells (NSCs possess the ability to self-renew and differentiate into both neurons and glia. However, the detailed mechanisms underlying NSC fate decisions are not well understood. Recent work suggest that the interaction between cell-type specific transcription factors and microRNAs (miRNAs is important as resident neural stem/progenitor cells give rise to functionally mature neurons. Recently, we demonstrated that the transcriptional repressor REST (RE1-silencing transcription factor is essential to prevent precocious neuronal differentiation and maintain NSC self-renewal in the adult hippocampus. Here we show that REST is required for orchestrating the expression of distinct subsets of miRNAs in primary mouse NSC cultures, a physiologically relevant cell type. Using miRNA array profiling, we identified known REST-regulated miRNA genes, as well as previously uncharacterized REST-dependent miRNAs. Interestingly, REST-regulated miRNAs undergo dynamic expression changes under differentiation conditions over time, but not under proliferation conditions. These results suggest that REST functions in a context-dependent manner through its target miRNAs for mediating neuronal production.

  19. Lifestyle profile assessment in active and non-active hypertensive women

    N. R. Cavichia

    2016-05-01

    Full Text Available The present study aimed to evaluate the lifestyle´s profile of 30 hypertensive women practitioners and nonpractitioners of physical activity in the city of Sinop/MT. We used the questionnaire Profile of Single Lifestyle (PSL consists of three issues of the components of Nutrition (N, Physical Activity (PA, Preventive Behavior (PB, Social Networking (SN and Stress Management (SM with scores ranging from 0 to 3 points and score calculated by the sum of questions divided by the number of questions. The data were analyzed statistically with a significance of 5%. The average of the active components of PSL (N = 2,07, PA = 2,04, PB = 2,18, SN = 2,38 and SM = 2,42 and average overall score of 2,16 inactive (N = 1,73, AF = 1,33, PB = 2,40, RS = 2,02 and SN = 2,09 and average score 1,86. In the comparison between groups all components were significant different. It was concluded that the profile of the active lifestyle of hypertensive women have significantly higher values than non-active women

  20. EFFECTS OF INTERFERON THERAPY UPON IMMUNE MARKER PROFILE AND ENZYMATIC ACTIVITY IN PERIPHERAL BLOOD LYMPHOCYTES OF PATIENTS WITH RENAL CANCER

    L. M. Kurtasova

    2014-01-01

    Full Text Available We have observed forty-four patients with metastatic renal cancer before and after interferon therapy. Immune markers of of peripheral blood lymphocytes were determined by flow cytometry. Activity of NAD (P-dependent dehydrogenase in blood lymphocytes was studied by means of bioluminescence technique. Changes of immune marker profiles and enzymatic activities of peripheral blood lymphocytes were found in patients with renal cancer after a course of interferon therapy.

  1. Complement profile and activation mechanisms by different LDL apheresis systems.

    Hovland, Anders; Hardersen, Randolf; Nielsen, Erik Waage; Enebakk, Terje; Christiansen, Dorte; Ludviksen, Judith Krey; Mollnes, Tom Eirik; Lappegård, Knut Tore

    2012-07-01

    Extracorporeal removal of low-density lipoprotein (LDL) cholesterol by means of selective LDL apheresis is indicated in otherwise uncontrolled familial hypercholesterolemia. During blood-biomaterial interaction other constituents than the LDL particles are affected, including the complement system. We set up an ex vivo model in which human whole blood was passed through an LDL apheresis system with one of three different apheresis columns: whole blood adsorption, plasma adsorption and plasma filtration. The concentrations of complement activation products revealed distinctly different patterns of activation and adsorption by the different systems. Evaluated as the final common terminal complement complex (TCC) the whole blood system was inert, in contrast to the plasma systems, which generated substantial and equal amounts of TCC. Initial classical pathway activation was revealed equally for both plasma systems as increases in the C1rs-C1inh complex and C4d. Alternative pathway activation (Bb) was most pronounced for the plasma adsorption system. Although the anaphylatoxins (C3a and C5a) were equally generated by the two plasma separation systems, they were efficiently adsorbed to the plasma adsorption column before the "outlet", whereas they were left free in the plasma in the filtration system. Consequently, during blood-biomaterial interaction in LDL apheresis the complement system is modulated in different manners depending on the device composition. PMID:22373816

  2. Constructing bioactive peptides with pH-dependent activities

    Tu, Zhigang; Volk, Melanie; Shah, Khushali; Clerkin, Kevin; Liang, Jun F.

    2009-01-01

    Many bioactive peptides are featured by their arginine and lysine rich contents. In this study, lysine and arginine residues in lytic peptides were selectively replaced by histidines. Although resulted histidine-containing lytic peptides had decreased activity, they did show pH-dependent cytotoxicity. The activity of the constructed histidine-containing lytic peptides increased 2 ~ 8 times as the solution pH changed from of 7.4 to 5.5. More importantly, these histidine-containing peptides mai...

  3. Weekend activities of czech families - depending on a season

    HOLÁ, Věra

    2009-01-01

    In my work, I focused on activities in Czech families during Saturday and Sunday, depending on season. Theoretical part summarises present knowledge to this theme from literature and other sources. The main contens of second part is analysis of data, obtained from investigation in families using selected methods {--} questionary, interview, observation. Reported data are summarized in tables and demonstrated in graphs. From comparison of weekend activities of mothers and fathers, it ensued, t...

  4. Activity-dependent modulation of neural circuit synaptic connectivity

    Charles R Tessier

    2009-07-01

    Full Text Available In many nervous systems, the establishment of neural circuits is known to proceed via a two-stage process; 1 early, activity-independent wiring to produce a rough map characterized by excessive synaptic connections, and 2 subsequent, use-dependent pruning to eliminate inappropriate connections and reinforce maintained synapses. In invertebrates, however, evidence of the activity-dependent phase of synaptic refinement has been elusive, and the dogma has long been that invertebrate circuits are “hard-wired” in a purely activity-independent manner. This conclusion has been challenged recently through the use of new transgenic tools employed in the powerful Drosophila system, which have allowed unprecedented temporal control and single neuron imaging resolution. These recent studies reveal that activity-dependent mechanisms are indeed required to refine circuit maps in Drosophila during precise, restricted windows of late-phase development. Such mechanisms of circuit refinement may be key to understanding a number of human neurological diseases, including developmental disorders such as Fragile X syndrome (FXS and autism, which are hypothesized to result from defects in synaptic connectivity and activity-dependent circuit function. This review focuses on our current understanding of activity-dependent synaptic connectivity in Drosophila, primarily through analyzing the role of the fragile X mental retardation protein (FMRP in the Drosophila FXS disease model. The particular emphasis of this review is on the expanding array of new genetically-encoded tools that are allowing cellular events and molecular players to be dissected with ever greater precision and detail.

  5. Substrate-Competitive Activity-Based Profiling of Ester Prodrug Activating Enzymes.

    Xu, Hao; Majmudar, Jaimeen D; Davda, Dahvid; Ghanakota, Phani; Kim, Ki H; Carlson, Heather A; Showalter, Hollis D; Martin, Brent R; Amidon, Gordon L

    2015-09-01

    Understanding the mechanistic basis of prodrug delivery and activation is critical for establishing species-specific prodrug sensitivities necessary for evaluating preclinical animal models and potential drug-drug interactions. Despite significant adoption of prodrug methodologies for enhanced pharmacokinetics, functional annotation of prodrug activating enzymes is laborious and often unaddressed. Activity-based protein profiling (ABPP) describes an emerging chemoproteomic approach to assay active site occupancy within a mechanistically similar enzyme class in native proteomes. The serine hydrolase enzyme family is broadly reactive with reporter-linked fluorophosphonates, which have shown to provide a mechanism-based covalent labeling strategy to assay the activation state and active site occupancy of cellular serine amidases, esterases, and thioesterases. Here we describe a modified ABPP approach using direct substrate competition to identify activating enzymes for an ethyl ester prodrug, the influenza neuraminidase inhibitor oseltamivir. Substrate-competitive ABPP analysis identified carboxylesterase 1 (CES1) as an oseltamivir-activating enzyme in intestinal cell homogenates. Saturating concentrations of oseltamivir lead to a four-fold reduction in the observed rate constant for CES1 inactivation by fluorophosphonates. WWL50, a reported carbamate inhibitor of mouse CES1, blocked oseltamivir hydrolysis activity in human cell homogenates, confirming CES1 is the primary prodrug activating enzyme for oseltamivir in human liver and intestinal cell lines. The related carbamate inhibitor WWL79 inhibited mouse but not human CES1, providing a series of probes for analyzing prodrug activation mechanisms in different preclinical models. Overall, we present a substrate-competitive activity-based profiling approach for broadly surveying candidate prodrug hydrolyzing enzymes and outline the kinetic parameters for activating enzyme discovery, ester prodrug design, and

  6. Substrate-competitive activity-based profiling of ester prodrug activating enzymes

    Xu, Hao; Majmudar, Jaimeen D.; Davda, Dahvid; Ghanakota, Phani; Kim, Ki H.; Carlson, Heather A.; Showalter, Hollis D.; Martin, Brent R.; Amidon, Gordon L.

    2015-01-01

    Understanding the mechanistic basis of prodrug delivery and activation is critical for establishing species-specific prodrug sensitivities necessary for evaluating pre-clinical animal models and potential drug-drug interactions. Despite significant adoption of prodrug methodologies for enhanced pharmacokinetics, functional annotation of prodrug activating enzymes is laborious and often unaddressed. Activity-based protein profiling (ABPP) describes an emerging chemoproteomic approach to assay active site occupancy within a mechanistically similar enzyme class in native proteomes. The serine hydrolase enzyme family is broadly reactive with reporter-linked fluorophosphonates, which have shown to provide a mechanism-based covalent labeling strategy to assay the activation state and active site occupancy of cellular serine amidases, esterases, and thioesterases. Here we describe a modified ABPP approach using direct substrate competition to identify activating enzymes for an ethyl ester prodrug, the influenza neuraminidase inhibitor oseltamivir. Substrate-competitive ABPP analysis identified carboxylesterase 1 (CES1) as an oseltamivir-activating enzyme in intestinal cell homogenates. Saturating concentrations of oseltamivir lead to a 4-fold reduction in the observed rate constant for CES1 inactivation by fluorophosphonates. WWL50, a reported carbamate inhibitor of mouse CES1, blocked oseltamivir hydrolysis activity in human cell homogenates, confirming CES1 is the primary prodrug activating enzyme for oseltamivir in human liver and intestinal cell lines. The related carbamate inhibitor WWL79 inhibited mouse, but not human CES1, providing a series of probes for analyzing prodrug activation mechanisms in different preclinical models. Overall, we present a substrate-competitive activity-based profiling approach for broadly surveying candidate prodrug hydrolyzing enzymes and outline the kinetic parameters for activating enzyme discovery, ester prodrug design and preclinical

  7. Chloride dependence of hyperpolarization-activated chloride channel gates.

    Pusch, M; Jordt, S E; Stein, V; Jentsch, T J

    1999-03-01

    1. ClC proteins are a class of voltage-dependent Cl- channels with several members mutated in human diseases. The prototype ClC-0 Torpedo channel is a dimeric protein; each subunit forms a pore that can gate independently from the other one. A common slower gating mechanism acts on both pores simultaneously; slow gating activates ClC-0 at hyperpolarized voltages. The ClC-2 Cl- channel is also activated by hyperpolarization, as are some ClC-1 mutants (e.g. D136G) and wild-type (WT) ClC-1 at certain pH values. 2. We studied the dependence on internal Cl- ([Cl-]i) of the hyperpolarization-activated gates of several ClC channels (WT ClC-0, ClC-0 mutant P522G, ClC-1 mutant D136G and an N-terminal deletion mutant of ClC-2), by patch clamping channels expressed in Xenopus oocytes. 3. With all these channels, reducing [Cl-]i shifted activation to more negative voltages and reduced the maximal activation at most negative voltages. 4. We also investigated the external halide dependence of WT ClC-2 using two-electrode voltage-clamp recording. Reducing external Cl- ([Cl-]o) activated ClC-2 currents. Replacing [Cl-]o by the less permeant Br- reduced channel activity and accelerated deactivation. 5. Gating of the ClC-2 mutant K566Q in normal [Cl-]o resembled that of WT ClC-2 in low [Cl-]o, i.e. channels had a considerable open probability (Po) at resting membrane potential. Substituting external Cl- by Br- or I- led to a decrease in Po. 6. The [Cl-]i dependence of the hyperpolarization-activated gates of various ClC channels suggests a similar gating mechanism, and raises the possibility that the gating charge for the hyperpolarization-activated gate is provided by Cl-. 7. The external halide dependence of hyperpolarization-activated gating of ClC-2 suggests that it is mediated or modulated by anions as in other ClC channels. In contrast to the depolarization-activated fast gates of ClC-0 and ClC-1, the absence of Cl- favours channel opening. Lysine 556 may be important for the

  8. Alcohol dependence and anxiety increase error-related brain activity.

    Schellekens, A.F.A.; Bruijn, E.R. de; Lankveld, C.A. van; Hulstijn, W.; Buitelaar, J.K.; Jong, C.A.J. de; Verkes, R.J.

    2010-01-01

    AIMS: Detection of errors is crucial for efficient goal-directed behaviour. The ability to monitor behaviour is found to be diminished in patients with substance dependence, as reflected in decreased error-related brain activity, i.e. error-related negativity (ERN). The ERN is also decreased in othe

  9. Alcohol dependence and anxiety increase error-related brain activity

    Schellekens, A.F.A.; Bruijn, E.R.A. de; Lankveld, C.A.A. van; Hulstijn, W.; Buitelaar, J.K.; Jong, C.A.J. de; Verkes, R.J.

    2010-01-01

    Aims Detection of errors is crucial for efficient goal-directed behaviour. The ability to monitor behaviour is found to be diminished in patients with substance dependence, as reflected in decreased error-related brain activity, i.e. error-related negativity (ERN). The ERN is also decreased in other

  10. Detecting actively translated open reading frames in ribosome profiling data.

    Calviello, Lorenzo; Mukherjee, Neelanjan; Wyler, Emanuel; Zauber, Henrik; Hirsekorn, Antje; Selbach, Matthias; Landthaler, Markus; Obermayer, Benedikt; Ohler, Uwe

    2016-02-01

    RNA-sequencing protocols can quantify gene expression regulation from transcription to protein synthesis. Ribosome profiling (Ribo-seq) maps the positions of translating ribosomes over the entire transcriptome. We have developed RiboTaper (available at https://ohlerlab.mdc-berlin.de/software/), a rigorous statistical approach that identifies translated regions on the basis of the characteristic three-nucleotide periodicity of Ribo-seq data. We used RiboTaper with deep Ribo-seq data from HEK293 cells to derive an extensive map of translation that covered open reading frame (ORF) annotations for more than 11,000 protein-coding genes. We also found distinct ribosomal signatures for several hundred upstream ORFs and ORFs in annotated noncoding genes (ncORFs). Mass spectrometry data confirmed that RiboTaper achieved excellent coverage of the cellular proteome. Although dozens of novel peptide products were validated in this manner, few of the currently annotated long noncoding RNAs appeared to encode stable polypeptides. RiboTaper is a powerful method for comprehensive de novo identification of actively used ORFs from Ribo-seq data. PMID:26657557

  11. Illustrating the Effect of pH on Enzyme Activity Using Gibbs Energy Profiles

    Bearne, Stephen L.

    2014-01-01

    Gibbs energy profiles provide students with a visual representation of the energy changes that occur during enzyme catalysis, making such profiles useful as teaching and learning tools. Traditional kinetic topics, such as the effect of pH on enzyme activity, are often not discussed in terms of Gibbs energy profiles. Herein, the symbolism of Gibbs…

  12. Dysregulation of Macrophage Activation Profiles by Engineered Nanoparticles

    Kodali, Vamsi; Littke, Matthew H.; Tilton, Susan C.; Teeguarden, Justin G.; Shi, Liang; Frevert, Charles W.; Wang, Wei; Pounds, Joel G.; Thrall, Brian D.

    2013-08-27

    Although the potential human health impacts from exposure to engineered nanoparticles (ENPs) are uncertain, past epidemiological studies have established correlations between exposure to ambient air pollution particulates and the incidence of pneumonia and lung infections. Using amorphous silica and superparamagnetic iron oxide (SPIO) as model high production volume ENPs, we examined how macrophage activation by bacterial lipopolysaccharide (LPS) or the lung pathogen Streptococcus pneumoniae is altered by ENP pretreatment. Neither silica nor SPIO treatment elicited direct cytotoxic or pro-inflammatory effects in bone marrow-derived macrophages. However, pretreatment of macrophages with SPIO caused extensive reprogramming of nearly 500 genes regulated in response to LPS challenge, hallmarked by exaggerated activation of oxidative stress response pathways and suppressed activation of both pro- and anti-inflammatory pathways. Silica pretreatment altered regulation of only 67 genes, but there was strong correlation with gene sets affected by SPIO. Macrophages exposed to SPIO displayed a phenotype suggesting an impaired ability to transition from an M1 to M2-like activation state, characterized by suppressed IL-10 induction, enhanced TNFα production, and diminished phagocytic activity toward S. pneumoniae. Studies in macrophages deficient in scavenger receptor A (SR-A) showed SR-A participates in cell uptake of both the ENPs and S. pneumonia and co-regulates the anti-inflammatory IL-10 pathway. Thus, mechanisms for dysregulation of innate immunity exist by virtue that common receptor recognition pathways are used by some ENPs and pathogenic bacteria, although the extent of transcriptional reprogramming of macrophage function depends on the physicochemical properties of the ENP after internalization. Our results also illustrate that biological effects of ENPs may be indirectly manifested only after challenging normal cell function. Finally, nanotoxicology screening

  13. Future body mass index modelling based on macronutrient profiles and physical activity

    Cundiff David K

    2012-10-01

    Full Text Available Abstract Background An accurate system of determining the relationship of macronutrient profiles of foods and beverages to the long-term weight impacts of foods is necessary for evidence-based, unbiased front-of-the-package food labels. Methods Data sets on diet, physical activity, and BMI came from the Food and Agriculture Organization (FAO, the World Health Organization (WHO, the Diabetes Control and Complications Trial (DCCT, and Epidemiology Diabetes Intervention and Complications (EDIC. To predict future BMI of individuals, multiple regression derived FAO/WHO and DCCT/EDIC formulas related macronutrient profiles and physical activity (independent variables to BMI change/year (dependent variable. Similar formulas without physical activity related macronutrient profiles of individual foods and beverages to four-year weight impacts of those items and compared those forecasts to published food group profiling estimates from three large prospective studies by Harvard nutritional epidemiologists. Results FAO/WHO food and beverage formula: four-year weight impact (pounds=(0.07710 alcohol g+11.95 (381.7+carbohydrates g per serving*4/(2,613+kilocalories per serving–304.9 (30.38+dietary fiber g per serving/(2,613+kilocalories per serving+19.73 (84.44+total fat g*9/(2,613+kilocalories per serving–68.57 (20.45+PUFA g per serving*9/(2,613+kilocalories per serving*2.941–12.78 (n=334, R2=0.29, P 2=0.03, P P = 0.0004. Formula predictions did not correlate with food group profiling findings for potatoes and dairy products (n=10, r= −0.33 P=0.36. A formula based diet and exercise analysis tool is available to researchers and individuals: http://thehealtheconomy.com/healthTool/. Conclusions Two multiple regression derived formulas from dissimilar databases produced markedly similar estimates of future BMI for 1,055 individuals with type 1 diabetes and female and male cohorts from 167 countries. These formulas predicted the long-term weight impacts of

  14. Activity-dependent plasticity of hippocampal place maps.

    Schoenenberger, Philipp; O'Neill, Joseph; Csicsvari, Jozsef

    2016-01-01

    Hippocampal neurons encode a cognitive map of space. These maps are thought to be updated during learning and in response to changes in the environment through activity-dependent synaptic plasticity. Here we examine how changes in activity influence spatial coding in rats using halorhodopsin-mediated, spatially selective optogenetic silencing. Halorhoposin stimulation leads to light-induced suppression in many place cells and interneurons; some place cells increase their firing through disinhibition, whereas some show no effect. We find that place fields of the unaffected subpopulation remain stable. On the other hand, place fields of suppressed place cells were unstable, showing remapping across sessions before and after optogenetic inhibition. Disinhibited place cells had stable maps but sustained an elevated firing rate. These findings suggest that place representation in the hippocampus is constantly governed by activity-dependent processes, and that disinhibition may provide a mechanism for rate remapping. PMID:27282121

  15. Energy Dependence of Profile Functions in $\\rm{p\\bar p}$ and $\\rm pp$ Scattering

    Kohara, Anderson Kendi; Kodama, Takeshi

    2013-01-01

    We construct analytical forms in the impact parameter $b$-space for the real and imaginary amplitudes describing elastic pp and $\\rm p \\bar p $ scattering. The amplitudes converted analytically to the momentum transfer $t$-space have magnitudes, slopes, curvatures, zeros, signs, obeying phenomenological and theoretical expectations, and describe with high precision all details of the data, in the full-t range, and for energies from 20 GeV to 7 TeV. The connection of forward with large-$|t|$ behavior allows precise determination of total cross-sections, slopes and other scattering parameters. We study the properties and the energy dependence of the $b$-space profile functions, observing that the real part has fundamental influence in the structure of $d\\sigma/dt$ at intermediate and large $|t|$ values. We discuss the 540/546 GeV and 1.8/1.96 TeV data from CERN SPS and Fermilab TEVATRON and the 7 TeV results from TOTEM measurements at LHC, and investigate the extrapolation to 14 TeV and higher energies.

  16. Solar activity dependence of nightside aurora in winter conditions

    Zhou, Su; Luan, Xiaoli; Dou, Xiankang

    2016-02-01

    The dependence of the nightside (21:00-03:00 MLT; magnetic local time) auroral energy flux on solar activity was quantitatively studied for winter/dark and geomagnetically quiet conditions. Using data combined from Thermosphere, Ionosphere, Mesosphere Energetics and Dynamics/Global Ultraviolet Imager and Defense Meteorological Satellite Program/Special Sensor Ultraviolet Spectrographic Imager observations, we separated the effects of geomagnetic activity from those of solar flux on the nightside auroral precipitation. The results showed that the nightside auroral power was reduced by ~42% in solar maximum (F10.7 = 200 sfu; solar flux unit 1 sfu = 10-22 W m-2 Hz-1) with respect to that under solar minimum (F10.7 = 70 sfu) for the Kp = 1 condition, and this change rate became less (~21%) for the Kp = 3 condition. In addition, the solar cycle dependence of nightside auroral power was similar with that from both the premidnight (21:00-23:00 MLT) and postmidnight (01:00-03:00 MLT) sectors. These results indicated that as the ionospheric ionization increases with the enhanced auroral and geomagnetic activities, the solar activity dependences of nightside auroral power become weaker, at least under geomagnetically quiet conditions.

  17. Comparison of JET and DIII-D temperature and density profile shapes and their parametric dependencies

    Goal was to develop a scaling expression which adequately describes profiles in existing tokamaks and which could be used to predict plasma profile shapes and magnitudes for future devices (such as ITER and TPX) without the need for a plasma transport model. This paper presents a multi-machine feasibility study of this goal. We present an initial assessment of an effort to derive an empirical expression for the normalized plasma electron temperature and electron density profile in terms of global quantities. (Global variables were used since they allowed a large enough database to be assembled for this statistical study.) Data from both JET and DIII-D were obtained in a single-null configuration with an expanded boundary divertor. The density profile parameterization indicates that as the plasma current is increased, the ne profile broadens and the edge gradient increases; this is consistent with JET and DIII-D operations. The Te profile broadens as the RF power is deposited farther off-axis. For both Te and ne profiles, the DIII-D profiles are more peaked than the JET profiles. The probable ITER profiles are discussed. 3 figs

  18. Time dependent measurements and calculations of field profile in the PBFA-II ion diode

    The reduction of the effective anode cathode (AK) gap during an applied-B ion diode pulse is driven by the diamagnetic effect of EXB drifting electrons in the sheath between the virtual cathode and the anode, and may be assisted by fluctuations that enable electrons to cross magnetic field lines. The dynamics of the sheath and the resulting AK gap are manifested in the time and space dependence of the electric field across the gap. The authors are studying the electric field profile in the PBFA-II ion diode with a goal of improving the understanding of acceleration gap dynamics, leading to improved power coupling to the ion beam. The cylindrically-symmetric PBFA-II ion diode accelerates ions radially inward, using a LiF ion source to generate a lithium beam with approximately 9 MeV peak energy, current densities up to 1 kA/cm2. The initial AK gap is typically 20 mm. They measure the accelerating electric field from the Stark shift of the LiI 2s-2p transition. The line emission is collected at four radii in the AK gap using fiber optics and the light from each radius is injected into a streaked spectrograph. Thus, on a single PBFA-II shot they acquire four spectra, each with 1 nsec time resolution, approximately 1 A spectral resolution, and each corresponding to a different radial location with a resolution of about 2 mm in the AK gap. The electric field is obtained from the measured Stark shift using calculations of the emission pattern that take into account both the electric and magnetic field and polarization. The electric field is typically constant across the gap at the onset of ion current growth. When the ion current becomes large, the field becomes larger on the anode side of the gap as the electron sheath thickness grows. The peak field observed is greater than 10 MV/cm, the highest field ever measured with the Stark effect. They compare the field profile measurements with calculations performed using two different computer codes

  19. Comprehensive Analysis of PPARα-Dependent Regulation of Hepatic Lipid Metabolism by Expression Profiling

    Maryam Rakhshandehroo

    2007-09-01

    Full Text Available PPARα is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARα in hepatic lipid metabolism, many PPARα-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPARα-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPARα target genes, livers from several animal studies in which PPARα was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPARα-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPARα-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip, electron-transferring-flavoprotein β polypeptide (Etfb, electron-transferring-flavoprotein dehydrogenase (Etfdh, phosphatidylcholine transfer protein (Pctp, endothelial lipase (EL, Lipg, adipose triglyceride lipase (Pnpla2, hormone-sensitive lipase (HSL, Lipe, and monoglyceride lipase (Mgll. Using an in silico screening approach, one or more PPAR response elements (PPREs were identified in each of these genes. Regulation of Pnpla2, Lipe, and Mgll, which are involved in triglyceride hydrolysis, was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPARα agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPARα. Our study illustrates the power of transcriptional profiling to uncover novel PPARα-regulated genes and pathways in liver.

  20. Dependence of the outer density profiles of halos on their mass accretion rate

    We present a systematic study of the density profiles of ΛCDM halos, focusing on the outer regions, 0.1 < r/R vir < 9. We show that the median and mean profiles of halo samples of a given peak height exhibit significant deviations from the universal analytic profiles discussed previously in the literature, such as the Navarro-Frenk-White and Einasto profiles, at radii r ≳ 0.5R 200m. In particular, at these radii the logarithmic slope of the median density profiles of massive or rapidly accreting halos steepens more sharply than predicted. The steepest slope of the profiles occurs at r ≈ R 200m, and its absolute value increases with increasing peak height or mass accretion rate, reaching slopes of –4 and steeper. Importantly, we find that the outermost density profiles at r ≳ R 200m are remarkably self-similar when radii are rescaled by R 200m. This self-similarity indicates that radii defined with respect to the mean density are preferred for describing the structure and evolution of the outer profiles. However, the inner density profiles are most self-similar when radii are rescaled by R 200c. We propose a new fitting formula that describes the median and mean profiles of halo samples selected by their peak height or mass accretion rate with accuracy ≲ 10% at all radii, redshifts, and masses we studied, r ≲ 9R vir, 0 < z < 6, and M vir > 1.7 × 1010 h –1 M ☉. We discuss observational signatures of the profile features described above and show that the steepening of the outer profile should be detectable in future weak-lensing analyses of massive clusters. Such observations could be used to estimate the mass accretion rate of cluster halos.

  1. Stress versus temperature dependence of activation energies for creep

    Freed, A. D.; Raj, S. V.; Walker, K. P.

    1992-01-01

    The activation energy for creep at low stresses and elevated temperatures is associated with lattice diffusion, where the rate controlling mechanism for deformation is dislocation climb. At higher stresses and intermediate temperatures, the rate controlling mechanism changes from dislocation climb to obstacle-controlled dislocation glide. Along with this change in deformation mechanism occurs a change in the activation energy. When the rate controlling mechanism for deformation is obstacle-controlled dislocation glide, it is shown that a temperature-dependent Gibbs free energy does better than a stress-dependent Gibbs free energy in correlating steady-state creep data for both copper and LiF-22mol percent CaF2 hypereutectic salt.

  2. Stress versus temperature dependent activation energies in creep

    Freed, A. D.; Raj, S. V.; Walker, K. P.

    1990-01-01

    The activation energy for creep at low stresses and elevated temperatures is lattice diffusion, where the rate controlling mechanism for deformation is dislocation climb. At higher stresses and intermediate temperatures, the rate controlling mechanism changes from that of dislocation climb to one of obstacle-controlled dislocation glide. Along with this change, there occurs a change in the activation energy. It is shown that a temperature-dependent Gibbs free energy does a good job of correlating steady-state creep data, while a stress-dependent Gibbs free energy does a less desirable job of correlating the same data. Applications are made to copper and a LiF-22 mol. percent CaF2 hypereutectic salt.

  3. Online Activity Levels Are Related to Caffeine Dependency.

    Phillips, James G; Landhuis, C Erik; Shepherd, Daniel; Ogeil, Rowan P

    2016-05-01

    Online activity could serve in the future as behavioral markers of emotional states for computer systems (i.e., affective computing). Hence, this study considered relationships between self-reported stimulant use and online study patterns. Sixty-two undergraduate psychology students estimated their daily caffeine use, and this was related to study patterns as tracked by their use of a Learning Management System (Blackboard). Caffeine dependency was associated with less time spent online, lower rates of file access, and fewer online activities completed. Reduced breadth or depth of processing during work/study could be used as a behavioral marker of stimulant use. PMID:27096737

  4. Social interactions, spatial dependence, and children's activities: evidence from India

    Rubiana Chamarbagwala

    2009-01-01

    After controlling for a wide range of determinants of children's participation in work, school, and idleness, we examine whether or not there exists spatial dependence in children's activities in neighboring Indian districts. We find that correlation among neighboring districts' unobservables play a significant role in determining the proportion of children who attend school, work, and are idle in a district. We attribute a large part of spatially correlated unobservables to common social att...

  5. Quantitative Proteomic Profiling of Muscle Type-Dependent and Age-Dependent Protein Carbonylation in Rat Skeletal Muscle Mitochondria

    Feng, Juan; Xie, Hongwei; Meany, Danni L.; Thompson, LaDora V.; Arriaga, Edgar A.; Griffin, Timothy J.

    2008-01-01

    Carbonylation is a highly prevalent protein modification in skeletal muscle mitochondria, possibly contributing to its functional decline with age. Using quantitative proteomics, we identified mitochondrial proteins susceptible to carbonylation in a muscle type (slow- vs fast-twitch)-dependent and age-dependent manner from Fischer 344 rat skeletal muscle. Fast-twitch muscle contained twice as many carbonylated mitochondrial proteins than did slow-twitch muscle, with 22 proteins showing signif...

  6. The Effects of Physical Training on Blood Lipid Profiles in Adolescents with Insulin-Dependent Diabetes Mellitus.

    Campaigne, B. N.; And Others

    1985-01-01

    Fourteen adolescents with insulin-dependent diabetes mellitus (IDDM) participated in a 12-week exercise program to determine whether such training would bring about changes in blood lipid and lipoprotein profiles. The findings support the beneficial effects of regular exercise for individuals with IDDM. (MT)

  7. Pyrethroid Activity-Based Probes for Profiling Cytochrome P450 Activities Associated with Insecticide Interactions

    Ismail, Hanafy M.; O' Neill, Paul M.; Hong, David; Finn, Robert; Henderson, Colin; Wright, Aaron T.; Cravatt, Benjamin; Hemingway, Janet; Paine, Mark J.

    2014-01-18

    Pyrethroid insecticides are used to control a diverse spectrum of diseases spread by arthropods. We have developed a suite of pyrethroid mimetic activity based probes (PyABPs) to selectively label and identify P450s associated with pyrethroid metabolism. The probes were screened against pyrethroid metabolizing and non-metabolizing mosquito P450s, as well as rodent microsomes to measure labeling specificity, plus CPR and b5 knockout mouse livers to validate P450 activation and establish the role for b5 in probe activation. Using a deltamethrin mimetic PyABP we were able to profile active enzymes in rat liver microsomes and identify pyrethroid metabolizing enzymes in the target tissue. The most reactive enzyme was a P450, CYP2C11, which is known to metabolize deltamethrin. Furthermore, several other pyrethroid metabolizers were identified (CYPs 2C6, 3A4, 2C13 and 2D1) along with related detoxification enzymes, notably UDP-g’s 2B1 - 5, suggesting a network of associated pyrethroid metabolizing enzymes, or ‘pyrethrome’. Considering the central role that P450s play in metabolizing insecticides, we anticipate that PyABPs will aid the identification and profiling of P450s associated with insecticide pharmacology in a wide range of species, improving understanding of P450-insecticide interactions and aiding the development of new tools for disease control.

  8. Transcriptional profiling in C. elegans suggests DNA damage dependent apoptosis as an ancient function of the p53 family

    Rothblatt Jonathan

    2008-07-01

    Full Text Available Abstract Background In contrast to the three mammalian p53 family members, p53, which is generally involved in DNA damage responses, and p63 and p73 which are primarily needed for developmental regulation, cep-1 encodes for the single C. elegans p53-like gene. cep-1 acts as a transcription activator in a primordial p53 pathway that involves CEP-1 activation and the CEP-1 dependent transcriptional induction of the worm BH3 only domain encoding genes egl-1 and ced-13 to induce germ cell apoptosis. EGL-1 and CED-13 proteins inactivate Bcl-2 like CED-9 to trigger CED-4 and CED-3 caspase dependent germ cell apoptosis. To address the function of p53 in global transcriptional regulation we investigate genome-wide transcriptional responses upon DNA damage and cep-1 deficiency. Results Examining C. elegans expression profiles using whole genome Affymetrix GeneChip arrays, we found that 83 genes were induced more than two fold upon ionizing radiation (IR. None of these genes, with exception of an ATP ribosylase homolog, encode for known DNA repair genes. Using two independent cep-1 loss of function alleles we did not find genes regulated by cep-1 in the absence of IR. Among the IR-induced genes only three are dependent on cep-1, namely egl-1, ced-13 and a novel C. elegans specific gene. The majority of IR-induced genes appear to be involved in general stress responses, and qRT-PCR experiments indicate that they are mainly expressed in somatic tissues. Interestingly, we reveal an extensive overlap of gene expression changes occurring in response to DNA damage and in response to bacterial infection. Furthermore, many genes induced by IR are also transcriptionally regulated in longevity mutants suggesting that DNA damage and aging induce an overlapping stress response. Conclusion We performed genome-wide gene expression analyses which indicate that only a surprisingly small number of genes are regulated by CEP-1 and that DNA damage induced apoptosis via the

  9. Substrate and pH-Dependent Kinetic Profile of 3-Mercaptopropionate Dioxygenase from Pseudomonas aeruginosa.

    Fellner, Matthias; Aloi, Sekotilani; Tchesnokov, Egor P; Wilbanks, Sigurd M; Jameson, Guy N L

    2016-03-01

    Thiol dioxygenases catalyze the synthesis of sulfinic acids in a range of organisms from bacteria to mammals. A thiol dioxygenase from the bacterium Pseudomonas aeruginosa oxidizes both 3-mercaptopropionic acid and cysteine, with a ∼70 fold preference for 3-mercaptopropionic acid over all pHs. This substrate reactivity is widened compared to other thiol dioxygenases and was exploited in this investigation of the residues important for activity. A simple model incorporating two protonation events was used to fit profiles of the Michaelis-Menten parameters determined at different pH values for both substrates. The pKs determined using plots of kcat/Km differ at low pH, but not in a way easily attributable to protonation of the substrate alone and share a common value at higher pH. Plots of kcat versus pH are also quite different at low pH showing the monoprotonated ES complexes with 3-mercaptopropionic acid and cysteine have different pKs. At higher pH, kcat decreases sigmoidally with a similar pK regardless of substrate. Loss of reactivity at high pH is attributed to deprotonation of tyrosine 159 and its influence on dioxygen binding. A mechanism is proposed by which deprotonation of tyrosine 159 both blocks oxygen binding and concomitantly promotes cystine formation. Finally, the role of tyrosine 159 was further probed by production of a G95C variant that is able to form a cysteine-tyrosine crosslink homologous to that found in mammalian cysteine dioxygenases. Activity of this variant is severely impaired. Crystallography shows that when un-crosslinked, the cysteine thiol excludes tyrosine 159 from its native position, while kinetic analysis shows that the thioether bond impairs reactivity of the crosslinked form. PMID:26878277

  10. Dependence of Selected Water Quality Parameters on Flow Rates in River Profiles in the Czech Republic

    Eduard Hanslík

    2016-06-01

    The results show that in the monitored profiles, there is a direct relationship with flow rate in case of N-NO3-, suspended solids and O2. Temperature shows an inverse relationship with the flow rate. Other parameters show different relationship with the flow rate in individual monitored profiles or do not show statistically significant relation.

  11. Calcium-dependent activation of Pyk2 by hypoxia.

    Beitner-Johnson, Dana; Ferguson, Tsuneo; Rust, Randy T; Kobayashi, Shuichi; Millhorn, David E

    2002-02-01

    The Pyk2 tyrosine kinase can be activated by both calcium-dependent and calcium-independent mechanisms. Exposure to moderate hypoxia (5% O(2)) induced a rapid and persistent tyrosine phosphorylation of Pyk2 in pheochromocytoma (PC12) cells. Hypoxia and KCl-depolarization increased the phosphotyrosine content of Pyk2 by twofold and fourfold, respectively. Both of these effects were abolished in the absence of extracellular calcium. There was a modest activation of MAPK in parallel with the onset of Pyk2 phosphorylation. However, there was no detectable activation of either JNK or c-src, two other known downstream targets of Pyk2. Thus, exposure to hypoxia may selectively target specific subsets of Pyk2 signalling pathways. PMID:11781137

  12. Quantitative site-specific ADP-ribosylation profiling of DNA-dependent PARPs.

    Gagné, Jean-Philippe; Ethier, Chantal; Defoy, Daniel; Bourassa, Sylvie; Langelier, Marie-France; Riccio, Amanda A; Pascal, John M; Moon, Kyung-Mee; Foster, Leonard J; Ning, Zhibin; Figeys, Daniel; Droit, Arnaud; Poirier, Guy G

    2015-06-01

    An important feature of poly(ADP-ribose) polymerases (PARPs) is their ability to readily undergo automodification upon activation. Although a growing number of substrates were found to be poly(ADP-ribosyl)ated, including histones and several DNA damage response factors, PARPs themselves are still considered as the main acceptors of poly(ADP-ribose). By monitoring spectral counts of specific hydroxamic acid signatures generated after the conversion of the ADP-ribose modification onto peptides by hydroxylamine hydrolysis, we undertook a thorough mass spectrometry mapping of the glutamate and aspartate ADP-ribosylation sites onto automodified PARP-1, PARP-2 and PARP-3. Thousands of hydroxamic acid-conjugated peptides were identified with high confidence and ranked based on their spectral count. This semi-quantitative approach allowed us to locate the preferentially targeted residues in DNA-dependent PARPs. In contrast to what has been reported in the literature, automodification of PARP-1 is not predominantly targeted towards its BRCT domain. Our results show that interdomain linker regions that connect the BRCT to the WGR module and the WGR to the PRD domain undergo prominent ADP-ribosylation during PARP-1 automodification. We also found that PARP-1 efficiently automodifies the D-loop structure within its own catalytic fold. Interestingly, additional major ADP-ribosylation sites were identified in functional domains of PARP-1, including all three zinc fingers. Similar to PARP-1, specific residues located within the catalytic sites of PARP-2 and PARP-3 are major targets of automodification following their DNA-dependent activation. Together our results suggest that poly(ADP-ribosyl)ation hot spots make a dominant contribution to the overall automodification process. PMID:25800440

  13. Multiphasic profiles for voltage-dependent K+ channels: Reanalysis of data of MacKinnon and coworkers

    Nissen, Per

    2016-01-01

    In a study of the role that voltage-dependent K+ channels may have in the mechanosensation of living cells (Schmidt et al. Proc Soc Natl Acad Sci USA 109: 10352-10357. 2012), the data were as conventionally done fitted by a Boltzmann function. However, as also found for other data for ion channels, this interpretation must be rejected in favor of a multiphasic profile, a series of straight lines separated by discontinuous transitions, quite often in the form of noncontiguities (jumps). The data points in the present study are often very unevenly distributed around the curvilinear profiles. Thus, for 43 of the 75 profiles, the probability is less than 5% that the uneven distribution is due to chance, for 26 the probability is less than 1%, and for 12 the probability is less than 0.1%, giving a vanishingly low overall probability for all profiles. Especially at low voltages, the differences between the fits to curvilinear and multiphasic profiles may be huge. In the multiphasic profiles, adjacent lines are quit...

  14. Modification of the electron temperature profile depending on the heating power and plasma parameters

    Boronization of the vacuum chamber of the L-2M stellarator has resulted in modification of the electron temperature profile. In particular, a well-defined jump in the electron temperature to ∼ 100eV in a narrow region r/ r ∼ 0.05 is observed in the temperature profile at the plasma edge. In the present paper, the value and shape of the jump in Te are studied at different values of plasma parameters and ECR heating power

  15. Anorexia nervosa depends on adrenal sympathetic hyperactivity: opposite neuroautonomic profile of hyperinsulinism syndrome

    Lechin, Fuad; van der Dijs, Bertha; Pardey-Maldonado, Betty; Rivera, Jairo E; Baez, Scarlet; Lechin, Marcel E

    2010-01-01

    Objective The aim of our study was to determine the central and peripheral autonomic nervous system profiles underlying anorexia nervosa (AN) syndrome, given that affected patients present with the opposite clinical profile to that seen in the hyperinsulinism syndrome. Design We measured blood pressure and heart rate, as well as circulating neurotransmitters (noradrenaline, adrenaline, dopamine, plasma serotonin, and platelet serotonin), using high-performance liquid chromatography with elect...

  16. Radial dependence of line profile variability in seven O9--B0.5 stars

    Martins, F.; Marcolino, W.; D. J. Hillier; Donati, J.-F.; Bouret, J. -C.

    2014-01-01

    Massive stars show a variety of spectral variability: presence of discrete absorption components in UV P-Cygni profiles, optical line profile variability, X-ray variability, radial velocity modulations. Our goal is to study the spectral variability of single OB stars to better understand the relation between photospheric and wind variability. For that, we rely on high spectral resolution, high signal-to-noise ratio optical spectra collected with the spectrograph NARVAL on the Telescope Bernar...

  17. IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype

    Guiliano David

    2002-07-01

    Full Text Available Abstract Background "Alternatively-activated" macrophages are found in Th2-mediated inflammatory settings such as nematode infection and allergic pulmonary inflammation. Due in part to a lack of markers, these cells have not been well characterized in vivo and their function remains unknown. Results We have used murine macrophages elicited by nematode infection (NeMφ as a source of in vivo derived alternatively activated macrophages. Using three distinct yet complementary molecular approaches we have established a gene expression profile of alternatively activated macrophages and identified macrophage genes that are regulated in vivo by IL-4. First, genes abundantly expressed were identified by an expressed sequence tag strategy. Second, an array of 1176 known mouse genes was screened for differential expression between NeMφ from wild type or IL-4 deficient mice. Third, a subtractive library was screened to identify novel IL-4 dependent macrophage genes. Differential expression was confirmed by real time RT-PCR analysis. Conclusions Our data demonstrate that alternatively activated macrophages generated in vivo have a gene expression profile distinct from any macrophage population described to date. Several of the genes we identified, including those most abundantly expressed, have not previously been associated with macrophages and thus this study provides unique new information regarding the phenotype of macrophages found in Th2-mediated, chronic inflammatory settings. Our data also provide additional in vivo evidence for parallels between the inflammatory processes involved in nematode infection and allergy.

  18. Shaping inhibition: activity dependent structural plasticity of GABAergic synapses

    Pablo Mendez

    2014-10-01

    Full Text Available Inhibitory transmission through the neurotransmitter Ɣ-aminobutyric acid (GABA shapes network activity in the mammalian cerebral cortex by filtering synaptic incoming information and dictating the activity of principal cells. The incredibly diverse population of cortical neurons that use GABA as neurotransmitter shows an equally diverse range of mechanisms that regulate changes in the strength of GABAergic synaptic transmission and allow them to dynamically follow and command the activity of neuronal ensembles. Similarly to glutamatergic synaptic transmission, activity-dependent functional changes in inhibitory neurotransmission are accompanied by alterations in GABAergic synapse structure that range from morphological reorganization of postsynaptic density to de novo formation and elimination of inhibitory contacts. Here we review several aspects of structural plasticity of inhibitory synapses, including its induction by different forms of neuronal activity, behavioral and sensory experience and the molecular mechanisms and signaling pathways involved. We discuss the functional consequences of GABAergic synapse structural plasticity for information processing and memory formation in view of the heterogenous nature of the structural plasticity phenomena affecting inhibitory synapses impinging on somatic and dendritic compartments of cortical and hippocampal neurons.

  19. Voigt profile introduces optical depth dependent systematic errors - Detected in high resolution laboratory spectra of water

    Birk, Manfred; Wagner, Georg

    2016-02-01

    The Voigt profile commonly used in radiative transfer modeling of Earth's and planets' atmospheres for remote sensing/climate modeling produces systematic errors so far not accounted for. Saturated lines are systematically too narrow when calculated from pressure broadening parameters based on the analysis of laboratory data with the Voigt profile. This is caused by line narrowing effects leading to systematically too small fitted broadening parameters when applying the Voigt profile. These effective values are still valid to model non-saturated lines with sufficient accuracy. Saturated lines dominated by the wings of the line profile are sufficiently accurately modeled with a Voigt profile with the correct broadening parameters and are thus systematically too narrow when calculated with the effective values. The systematic error was quantified by mid infrared laboratory spectroscopy of the water ν2 fundamental. Correct Voigt profile based pressure broadening parameters for saturated lines were 3-4% larger than the effective ones in the spectroscopic database. Impacts on remote sensing and climate modeling are expected. Combination of saturated and non-saturated lines in the spectroscopic analysis will quantify line narrowing with unprecedented precision.

  20. A memristor SPICE model accounting for synaptic activity dependence.

    Qingjiang Li

    Full Text Available In this work, we propose a new memristor SPICE model that accounts for the typical synaptic characteristics that have been previously demonstrated with practical memristive devices. We show that this model could account for both volatile and non-volatile memristance changes under distinct stimuli. We then demonstrate that our model is capable of supporting typical STDP with simple non-overlapping digital pulse pairs. Finally, we investigate the capability of our model to simulate the activity dependence dynamics of synaptic modification and present simulated results that are in excellent agreement with biological results.

  1. Activity-dependent neural plasticity from bench to bedside.

    Ganguly, Karunesh; Poo, Mu-Ming

    2013-10-30

    Much progress has been made in understanding how behavioral experience and neural activity can modify the structure and function of neural circuits during development and in the adult brain. Studies of physiological and molecular mechanisms underlying activity-dependent plasticity in animal models have suggested potential therapeutic approaches for a wide range of brain disorders in humans. Physiological and electrical stimulations as well as plasticity-modifying molecular agents may facilitate functional recovery by selectively enhancing existing neural circuits or promoting the formation of new functional circuits. Here, we review the advances in basic studies of neural plasticity mechanisms in developing and adult nervous systems and current clinical treatments that harness neural plasticity, and we offer perspectives on future development of plasticity-based therapy. PMID:24183023

  2. Activity-dependent neuronal model on complex networks.

    de Arcangelis, Lucilla; Herrmann, Hans J

    2012-01-01

    Neuronal avalanches are a novel mode of activity in neuronal networks, experimentally found in vitro and in vivo, and exhibit a robust critical behavior: these avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems. We present a recent model inspired in self-organized criticality, which consists of an electrical network with threshold firing, refractory period, and activity-dependent synaptic plasticity. The model reproduces the critical behavior of the distribution of avalanche sizes and durations measured experimentally. Moreover, the power spectra of the electrical signal reproduce very robustly the power law behavior found in human electroencephalogram (EEG) spectra. We implement this model on a variety of complex networks, i.e., regular, small-world, and scale-free and verify the robustness of the critical behavior. PMID:22470347

  3. Geometry-dependent viscosity reduction in sheared active fluids

    Słomka, Jonasz

    2016-01-01

    We investigate flow pattern formation and viscosity reduction mechanisms in active fluids by studying a generalized Navier-Stokes model that captures the experimentally observed bulk vortex dynamics in microbial suspensions. We present exact analytical solutions including stress-free vortex lattices and introduce a computational framework that allows the efficient treatment of previously intractable higher-order shear boundary conditions. Large-scale parameter scans identify the conditions for spontaneous flow symmetry breaking, geometry-dependent viscosity reduction and negative-viscosity states amenable to energy harvesting in confined suspensions. The theory uses only generic assumptions about the symmetries and long-wavelength structure of active stress tensors, suggesting that inviscid phases may be achievable in a broad class of non-equilibrium fluids by tuning confinement geometry and pattern scale selection.

  4. Reading in public libraries: space, reading activities and user profiles

    Sequeiros, Paula

    2013-01-01

    This single case research was developed within a public library in Porto, Portugal, Biblioteca Municipal Almeida Garrett. Its main objective was to understand how public library readers interact with space, the Internet technology and reading resources, and how these interactions shape the representations of what a public library is. This case was chosen because the library has a recent and renowned building, high reader use levels, and Internet access. The design of user profiles was an i...

  5. RELATIONSHIPS BETWEEN PHYSICAL EDUCATION STUDENTS' MOTIVATIONAL PROFILES, ENJOYMENT, STATE ANXIETY, AND SELF-REPORTED PHYSICAL ACTIVITY

    Sami Yli-Piipari

    2009-09-01

    Full Text Available The purpose of this study was to analyze motivational profiles based on the self-determination theory (Deci and Ryan, 2000 and how these profiles are related to physical education students' enjoyment, state anxiety, and physical activity. The participants, 429 sixth grade students (girls = 216; boys = 213 completed SMS, Sport Enjoyment Scale, PESAS, and Physical Activity Scale. Cluster analyses identified two motivational profiles: 1 the "High motivation profile", in which the students had high intrinsic and extrinsic motivation, and low levels of amotivation, and 2 the "Low motivation profile", in which the students had low intrinsic and extrinsic motivation, and low levels of amotivation. The students in the first cluster enjoyed physical education more and were physically more active. The results revealed that students may be motivated towards physical education lessons both intrinsically and extrinsically, and still experience enjoyment in physical education.

  6. Nanofiber diameter-dependent MAPK activity in osteoblasts.

    Jaiswal, Devina; Brown, Justin L

    2012-11-01

    The major challenge for bone tissue engineering lies in the fabrication of scaffolds that can mimic the extracellular matrix and promote osteogenesis. Electrospun fibers are being widely researched for this application due to high porosity, interconnectivity, and mechanical strength of the fibrous scaffolds. Electrospun poly methyl methacrylate (PMMA, 2.416 ± 0.100 μm) fibers were fabricated and etched using a 60% propylene glycol methyl ether acetate (PGMEA)/limonene (vol/vol) solution to obtain fiber diameters ranging from 2.5 to 0.5 μm in a time-dependent manner. The morphology of the fibrous scaffolds was evaluated using scanning electron microscopy and cellular compatibility with etchant-treated scaffold was assessed using immunoflurescence. Mitogen-activated protein kinases (MAPK) activation in response to different fiber diameter was evaluated with western blot as well as quantitative in-cell western. We report that electrospun micro-fibers can be etched to 0.552 ± 0.047 μm diameter without producing beads. Osteoblasts adhered to the fibers and a change in fiber diameter played a major role in modulating the activation of extracellular signal-regulated kinase (ERK) and p38 kinases with 0.882 ± 0.091 μm diameter fibers producing an inverse effect on ERK and p38 phosphorylation. These results indicate that nanofibers produced by wet etching can be effectively utilized to produce diameters that can differentially modulate MAPK activation patterns. PMID:22700490

  7. Protein profiling and histone deacetylation activities in somaclonal variants of oil palm (Elaeis guineensis Jacq.).

    Yaacob, Jamilah Syafawati; Loh, Hwei-San; Mat Taha, Rosna

    2013-01-01

    Mantled fruits as a result of somaclonal variation are often observed from the oil palm plantlets regenerated via tissue culture. The mantling of fruits with finger-like and thick outer coating phenotypes significantly reduces the seed size and oil content, posing a threat to oil palm planters, and may jeopardize the economic growth of countries that depend particularly on oil palm plantation. The molecular aspects of the occurrence of somaclonal variations are yet to be known, possibly due to gene repression such as DNA methylation, histone methylation and histone deacetylation. Histone deacetylases (HDACs), involved in eukaryotic gene regulation by catalyzing the acetyl groups are removal from lysine residues on histone, hence transcriptionally repress gene expression. This paper described the total protein polymorphism profiles of somaclonal variants of oil palm and the effects of histone deacetylation on this phenomenon. Parallel to the different phenotypes, the protein polymorphism profiles of the mantled samples (leaves, fruits, and florets) and the phenotypically normal samples were proven to be different. Higher HDAC activity was found in mantled leaf samples than in the phenotypically normal leaf samples, leading to a preliminary conclusion that histone deacetylation suppressed gene expression and contributed to the development of somaclonal variants. PMID:23844406

  8. Protein Profiling and Histone Deacetylation Activities in Somaclonal Variants of Oil Palm (Elaeis guineensis Jacq.

    Jamilah Syafawati Yaacob

    2013-01-01

    Full Text Available Mantled fruits as a result of somaclonal variation are often observed from the oil palm plantlets regenerated via tissue culture. The mantling of fruits with finger-like and thick outer coating phenotypes significantly reduces the seed size and oil content, posing a threat to oil palm planters, and may jeopardize the economic growth of countries that depend particularly on oil palm plantation. The molecular aspects of the occurrence of somaclonal variations are yet to be known, possibly due to gene repression such as DNA methylation, histone methylation and histone deacetylation. Histone deacetylases (HDACs, involved in eukaryotic gene regulation by catalyzing the acetyl groups are removal from lysine residues on histone, hence transcriptionally repress gene expression. This paper described the total protein polymorphism profiles of somaclonal variants of oil palm and the effects of histone deacetylation on this phenomenon. Parallel to the different phenotypes, the protein polymorphism profiles of the mantled samples (leaves, fruits, and florets and the phenotypically normal samples were proven to be different. Higher HDAC activity was found in mantled leaf samples than in the phenotypically normal leaf samples, leading to a preliminary conclusion that histone deacetylation suppressed gene expression and contributed to the development of somaclonal variants.

  9. Substance-dependent women attending a de-addiction center in North India: Sociodemographic and clinical profile

    Grover S

    2005-07-01

    Full Text Available Background: Treatment-seeking is limited in women substance abusers. Studying the sociodemographic and clinical profile of treatment-seeking substance-dependent women can help us to understand the problem better and respond appropriately in terms of primary and secondary prevention strategies. Aim: To study the sociodemographic and clinical profile of women attending a de-addiction centre in North India. Design and Methodology: Retrospective structured chart review of 35 women substance abusers. Results: The results indicated that a typical subject was urban (86%, married (63%, nuclear family (60%, based housewife (57%, educated up to school completion (54%, and having poor social support (57%. The common substances were opioids (60%, followed by alcohol (17%, and tobacco and benzodiazepines (11.5% each. The mean age at onset of substance use was 30.5 years, the mean duration of use was 9 years and mean duration to develop dependence was 5.5 years. The common reasons for initiating use were medical (63% and curiosity (34%. Comorbidity profile was: physical illness (34%, psychiatric illness (23% and dependence on another substance (14%. Only 20% had a family history of substance dependence. The social impairment ranged from 77% for social to 40% for financial and none for legal aspects. A typical subject had followed up 4.2 times in 8.4 months, while 54% were abstaining, 40% were continuing their substance dependence at the last follow up. Conclusions: The results suggest that the development of substance dependence in women is a combination of genetic, personal, and social vulnerability factors, including the drug culture of the social milieu and the poor social support. Comorbidity and impairment are common features.

  10. Efficacy of treatment in an opioid –dependent population group using the Maudsley Addiction Profile (MAP) tool

    Collins, Ruth; Boggs, Bob; Taggart, Noel; Kelly, Martin; Drillington, Aileen; Swanton, Ivy; Patterson, Diane

    2009-01-01

    A pilot study was performed to assess the effectiveness of treatment in an opioid dependent population using the Maudsley Addiction Profile (MAP) tool1. The primary outcome of the study was to assess if treatment had an effect on 1. Substance use (quantity and frequency of use), 2. Health risk behaviour (injecting and sharing injecting equipment), 3. Health symptoms (physical and psychological) and 4. Personal /Social functioning (relationships, employment and crime). A secondary outcome was ...

  11. ALIENATION, SENSATION SEEKING AND MULTIPHASIC PERSONALITY QUESTIONNAIRE PROFILE IN MEN BEING TREATED FOR ALCOHOL AND/OR OPIOID DEPENDENCE

    Mattoo, Surendra K.; Varma, Vijoy K.; Singh, Ram Avatar; Khurana, Hitesh; Kaur, Rajinder; Suresh K. Sharma

    2001-01-01

    Two hundred and thirty men, being treated for ICD-10 diagnosed dependence on alcohol, opioids or both, were studied 2-4 weeks after the last use of alcohol or opioids. Alienation Scale, Sensation Seeking Scale and Muliphasic Personality Questionnaire (MPQ), and selected sociodemographic and family history data were studied. All three groups showed high alienation (more in opioid cases), high sensation seeking (more in alcohol cases, more for boredom susceptibility), and a disturbed MPQ profil...

  12. The field-dependent shock profiles of a magnetorhelogical damper due to high impact: an experimental investigation

    This work proposes a new damper featuring magnetorheological fluid (MR damper) and presents its field-dependent damping forces due to high impact. To achieve this goal, a large MR damper, which can produce a damping force of 100 kN at 6 A, is designed and manufactured based on the analysis of the magnetic flux intensity of the damper. After identifying the field-dependent damping force levels of the manufactured MR damper, a hydraulic horizontal shock tester is established. This shock testing system consists of a velocity generator, impact mass, shock programmer, and test mass. The MR damper is installed at the end of the wall in the shock tester and tested under four different experimental conditions. The shock profile characteristics of the MR damper due to different impact velocities are investigated at various input current levels. In addition, the inner pressure of the MR damper during impact, which depends on the input’s current level, is evaluated at two positions that can represent the pressure drop that generates the damping force of the MR damper. It is demonstrated from this impact testing that the shock profiles can be changed by the magnitude of the input current applied to the MR damper. It directly indicates that a desired shock profile can be achieved by installing the MR damper associated with appropriate control logics to adjust the magnitude of the input current. (paper)

  13. Activity-Based Protein Profiling of Ammonia Monooxygenase in Nitrosomonas europaea.

    Bennett, Kristen; Sadler, Natalie C; Wright, Aaron T; Yeager, Chris; Hyman, Michael R

    2016-04-01

    Nitrosomonas europaea is an aerobic nitrifying bacterium that oxidizes ammonia (NH3) to nitrite (NO2 (-)) through the sequential activities of ammonia monooxygenase (AMO) and hydroxylamine dehydrogenase (HAO). Many alkynes are mechanism-based inactivators of AMO, and here we describe an activity-based protein profiling method for this enzyme using 1,7-octadiyne (17OD) as a probe. Inactivation of NH4 (+)-dependent O2 uptake by N. europaea by 17OD was time- and concentration-dependent. The effects of 17OD were specific for ammonia-oxidizing activity, andde novoprotein synthesis was required to reestablish this activity after cells were exposed to 17OD. Cells were reacted with Alexa Fluor 647 azide using a copper-catalyzed azide-alkyne cycloaddition (CuAAC) (click) reaction, solubilized, and analyzed by SDS-PAGE and infrared (IR) scanning. A fluorescent 28-kDa polypeptide was observed for cells previously exposed to 17OD but not for cells treated with either allylthiourea or acetylene prior to exposure to 17OD or for cells not previously exposed to 17OD. The fluorescent polypeptide was membrane associated and aggregated when heated with β-mercaptoethanol and SDS. The fluorescent polypeptide was also detected in cells pretreated with other diynes, but not in cells pretreated with structural homologs containing a single ethynyl functional group. The membrane fraction from 17OD-treated cells was conjugated with biotin-azide and solubilized in SDS. Streptavidin affinity-purified polypeptides were on-bead trypsin-digested, and amino acid sequences of the peptide fragments were determined by liquid chromatography-mass spectrometry (LC-MS) analysis. Peptide fragments from AmoA were the predominant peptides detected in 17OD-treated samples. In-gel digestion and matrix-assisted laser desorption ionization-tandem time of flight (MALDI-TOF/TOF) analyses also confirmed that the fluorescent 28-kDa polypeptide was AmoA. PMID:26826234

  14. Activity-based protein profiling of ammonia monooxygenase in Nitrosomonas europaea.

    Bennett, Kristen; Sadler, Natalie C.; Wright, Aaron T.; Yeager, Chris; Hyman, Michael R.

    2016-01-29

    Nitrosomonas europaea is an aerobic nitrifying bacterium that oxidizes ammonia (NH3) to nitrite (NO2-) through the sequential activities of ammonia monooxygenase (AMO) and hydroxylamine oxidoreductase (HAO). Many alkynes are mechanism-based inactivators of AMO and here we describe an activity-based protein profiling method for this enzyme using 1,7-octadiyne (17OD) as a probe. Inactivation of NH4+-dependent O2 uptake by N. europaea by 17OD was time- and concentration-dependent. The effects of 17OD were specific for ammonia-oxidizing activity and de novo protein synthesis was required to reestablish this activity after cells were exposed to 17OD. Cells were reacted with AlexaFluor 647-azide using a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, solubilized and analyzed by SDS-PAGE and IR scanning. A fluorescent 28 kDa polypeptide was observed for cells previously exposed to 17OD, but not for cells treated with either allylthiourea or acetylene prior to exposure to 17OD, or for cells not previously exposed to 17OD. The 28 kDa polypeptide was membrane-associated and aggregated when heated with β-mercaptoethanol and SDS. The fluorescent 28 kDa polypeptide was also detected in cells pretreated with other diynes, but not in cells pretreated with structural homologs containing a single ethynyl functional group. The membrane fraction from 17OD-treated cells was conjugated with biotin-azide and solubilized in SDS. Streptavidin affinity-purified polypeptides were on-bead trypsin-digested and amino acid sequences of the peptide fragments were determined by LC-MS analysis. Peptide fragments from amoA were the predominant peptides detected in 17OD-treated samples. In gel digestion and MALDI-TOF/TOF analysis also confirmed the fluorescent 28 kDa polypeptide was amoA.

  15. DS86 neutron dose: Monte Carlo analysis for depth profile of 152Eu activity in a large stone sample.

    Endo, S; Iwatani, K; Oka, T; Hoshi, M; Shizuma, K; Imanaka, T; Takada, J; Fujita, S; Hasai, H

    1999-06-01

    The depth profile of 152Eu activity induced in a large granite stone pillar by Hiroshima atomic bomb neutrons was calculated by a Monte Carlo N-Particle Transport Code (MCNP). The pillar was on the Motoyasu Bridge, located at a distance of 132 m (WSW) from the hypocenter. It was a square column with a horizontal sectional size of 82.5 cm x 82.5 cm and height of 179 cm. Twenty-one cells from the north to south surface at the central height of the column were specified for the calculation and 152Eu activities for each cell were calculated. The incident neutron spectrum was assumed to be the angular fluence data of the Dosimetry System 1986 (DS86). The angular dependence of the spectrum was taken into account by dividing the whole solid angle into twenty-six directions. The calculated depth profile of specific activity did not agree with the measured profile. A discrepancy was found in the absolute values at each depth with a mean multiplication factor of 0.58 and also in the shape of the relative profile. The results indicated that a reassessment of the neutron energy spectrum in DS86 is required for correct dose estimation. PMID:10494148

  16. Assessing Sources of Stress to Aquatic Ecosystems: Using Biomarkers and Bioindicators to Characterize Exodure-Response Profiles of Anthropogenic Activities

    Adams, S.M.

    1999-03-29

    Establishing causal relationships between sources of environmental stressors and aquatic ecosystem health if difficult because of the many biotic and abiotic factors which can influence or modify responses of biological systems to stress, the orders of magnitude involved in extrapolation over both spatial and temporal scales, and compensatory mechanisms such as density-dependent responses that operate in populations. To address the problem of establishing causality between stressors and effects on aquatic systems, a diagnostic approach, based on exposure-response profiles for various anthropogenic activities, was developed to help identify sources of stress responsible for effects on aquatic systems at ecological significant levels of biological organization (individual, population, community). To generate these exposure-effects profiles, biomarkers of exposure were plotted against bioindicators of corresponding effects for several major anthropogenic activities including petrochemical , pulp and paper, domestic sewage, mining operations, land-development activities, and agricultural activities. Biomarkers of exposure to environmental stressors varied depending on the type of anthropogenic activity involved. Bioindicator effects, however, including histopathological lesions, bioenergetic status, individual growth, reproductive impairment, and community-level responses were similar among many of the major anthropogenic activities. This approach is valuable to help identify and diagnose sources of stressors in environments impacted by multiple stressors. By identifying the types and sources of environmental stressors, aquatic ecosystems can be more effectively protected and managed to maintain acceptable levels of environmental quality and ecosystem fitness.

  17. Dose-dependent effects of dietary zinc oxide on bacterial communities and metabolic profiles in the ileum of weaned pigs.

    Pieper, R; Vahjen, W; Neumann, K; Van Kessel, A G; Zentek, J

    2012-10-01

    Pharmacological levels of zinc oxide (ZnO) can improve the health of weaning piglets and influence the intestinal microbiota. This experiment aimed at studying the dose-response effect of five dietary concentrations of ZnO on small intestinal bacteria and metabolite profiles. Fifteen piglets, weaned at 25 ± 1 days of age, were allocated into five groups according to body weight and litter. Diets were formulated to contain 50 (basal diet), 150, 250, 1000 and 2500 mg zinc/kg by adding analytical-grade (>98% purity) ZnO to the basal diet and fed ad libitum for 14 days after a 7-day adaptation period on the basal diet. Ileal bacterial community profiles were analysed by denaturing gradient gel electrophoresis and selected bacterial groups quantified by real-time PCR. Concentrations of ileal volatile fatty acids (VFA), D- and L-lactate and ammonia were determined. Species richness, Shannon diversity and evenness were significantly higher at high ZnO levels. Quantitative PCR revealed lowest total bacterial counts in the 50 mg/kg group. Increasing ZnO levels led to an increase (p = 0.017) in enterobacteria from log 4.0 cfu/g digesta (50 mg/kg) to log 6.7 cfu/g digesta (2500 mg/kg). Lactic acid bacteria were not influenced (p = 0.687) and clostridial cluster XIVa declined (p = 0.035) at highest ZnO level. Concentration of total, D- and L-lactate and propionate was not affected (p = 0.736, p = 0.290 and p = 0.630), but concentrations of ileal total VFA, acetate and butyrate increased markedly from 50 to 150 mg/kg and decreased with further increasing zinc levels and reached low levels again at 2500 mg/kg (p = 0.048, p = 0.048 and p = 0.097). Ammonia decreased (p < 0.006) with increasing dietary ZnO level. In conclusion, increasing levels of dietary ZnO had strong and dose-dependent effects on ileal bacterial community composition and activity, suggesting taxonomic variation in metabolic response to ZnO. PMID:21929727

  18. Multicomponent He I 10 830 Å profiles in an active filament

    Sasso, C.; Lagg, A.; Solanki, S. K.

    2011-02-01

    Aims: We present new spectropolarimetric observations of the chromospheric He i 10 830 Å multiplet observed in a filament during its phase of activity. Methods: The data were recorded with the new Tenerife Infrared Polarimeter (TIP-II) at the German Vacuum Tower Telescope (VTT) on 2005 May 18. We inverted the He Stokes profiles using multiple atmospheric components. Results: The observed He Stokes profiles display a remarkably wide variety of shapes. Most of the profiles show very broad Stokes I absorptions and complex and spatially variable Stokes V signatures. The inversion of the profiles shows evidence of different atmospheric blue- and redshifted components of the He i lines within the resolution element (~1 arcsec), with supersonic velocities of up to ~100 km s-1. Up to five different atmospheric components are found in the same profile. We show that even these complex profiles can be reliably inverted.

  19. Does the effectiveness of control measures depend on the influenza pandemic profile?

    Solen Kernéis

    Full Text Available BACKGROUND: Although strategies to contain influenza pandemics are well studied, the characterization and the implications of different geographical and temporal diffusion patterns of the pandemic have been given less attention. METHODOLOGY/MAIN FINDINGS: Using a well-documented metapopulation model incorporating air travel between 52 major world cities, we identified potential influenza pandemic diffusion profiles and examined how the impact of interventions might be affected by this heterogeneity. Clustering methods applied to a set of pandemic simulations, characterized by seven parameters related to the conditions of emergence that were varied following Latin hypercube sampling, were used to identify six pandemic profiles exhibiting different characteristics notably in terms of global burden (from 415 to >160 million of cases and duration (from 26 to 360 days. A multivariate sensitivity analysis showed that the transmission rate and proportion of susceptibles have a strong impact on the pandemic diffusion. The correlation between interventions and pandemic outcomes were analyzed for two specific profiles: a fast, massive pandemic and a slow building, long-lasting one. In both cases, the date of introduction for five control measures (masks, isolation, prophylactic or therapeutic use of antivirals, vaccination correlated strongly with pandemic outcomes. Conversely, the coverage and efficacy of these interventions only moderately correlated with pandemic outcomes in the case of a massive pandemic. Pre-pandemic vaccination influenced pandemic outcomes in both profiles, while travel restriction was the only measure without any measurable effect in either. CONCLUSIONS: our study highlights: (i the great heterogeneity in possible profiles of a future influenza pandemic; (ii the value of being well prepared in every country since a pandemic may have heavy consequences wherever and whenever it starts; (iii the need to quickly implement control

  20. The DNA methylation profile of activated human natural killer cells.

    Wiencke, John K; Butler, Rondi; Hsuang, George; Eliot, Melissa; Kim, Stephanie; Sepulveda, Manuel A; Siegel, Derick; Houseman, E Andres; Kelsey, Karl T

    2016-05-01

    Natural killer (NK) cells are now recognized to exhibit characteristics akin to cells of the adaptive immune system. The generation of adaptive memory is linked to epigenetic reprogramming including alterations in DNA methylation. The study herein found reproducible genome wide DNA methylation changes associated with human NK cell activation. Activation led predominately to CpG hypomethylation (81% of significant loci). Bioinformatics analysis confirmed that non-coding and gene-associated differentially methylated sites (DMS) are enriched for immune related functions (i.e., immune cell activation). Known DNA methylation-regulated immune loci were also identified in activated NK cells (e.g., TNFA, LTA, IL13, CSF2). Twenty-one loci were designated high priority and further investigated as potential markers of NK activation. BHLHE40 was identified as a viable candidate for which a droplet digital PCR assay for demethylation was developed. The assay revealed high demethylation in activated NK cells and low demethylation in naïve NK, T- and B-cells. We conclude the NK cell methylome is plastic with potential for remodeling. The differentially methylated region signature of activated NKs revealed similarities with T cell activation, but also provided unique biomarker candidates of NK activation, which could be useful in epigenome-wide association studies to interrogate the role of NK subtypes in global methylation changes associated with exposures and/or disease states. PMID:26967308

  1. Size-dependent catalytic activity of supported metal clusters

    Xu, Z.; Xiao, F.-S.; Purnell, S. K.; Alexeev, O.; Kawi, S.; Deutsch, S. E.; Gates, B. C.

    1994-11-01

    BECAUSE catalysis by metals is a surface phenomenon, many technological catalysts contain small (typically nanometre-sized) supported metal particles with a large fraction of the atoms exposed1. Many reactions, such as hydrocarbon hydrogenations, are structure-insensitive, proceeding at approximately the same rate on metal particles of various sizes provided that they are larger than about 1 nm and show bulk-like metallic behaviour1. But it is not known whether the catalytic properties of metal particles become size-dependent as the particles become so small that they are no longer metallic in character. Here we investigate the catalytic behaviour of precisely defined clusters of just four and six iridium atoms on solid supports. We find that the Ir4 and Ir6 clusters differ in catalytic activity both from each other and from metallic Ir particles. This raises the possibility of tailoring the catalytic behaviour of metal clusters by controlling the cluster size.

  2. A Solar Cycle Dependence of Nonlinearity in Magnetospheric Activity

    Johnson, Jay R; Wing, Simon

    2005-03-08

    The nonlinear dependencies inherent to the historical K(sub)p data stream (1932-2003) are examined using mutual information and cumulant based cost as discriminating statistics. The discriminating statistics are compared with surrogate data streams that are constructed using the corrected amplitude adjustment Fourier transform (CAAFT) method and capture the linear properties of the original K(sub)p data. Differences are regularly seen in the discriminating statistics a few years prior to solar minima, while no differences are apparent at the time of solar maximum. These results suggest that the dynamics of the magnetosphere tend to be more linear at solar maximum than at solar minimum. The strong nonlinear dependencies tend to peak on a timescale around 40-50 hours and are statistically significant up to one week. Because the solar wind driver variables, VB(sub)s and dynamical pressure exhibit a much shorter decorrelation time for nonlinearities, the results seem to indicate that the nonlinearity is related to internal magnetospheric dynamics. Moreover, the timescales for the nonlinearity seem to be on the same order as that for storm/ring current relaxation. We suggest that the strong solar wind driving that occurs around solar maximum dominates the magnetospheric dynamics suppressing the internal magnetospheric nonlinearity. On the other hand, in the descending phase of the solar cycle just prior to solar minimum, when magnetospheric activity is weaker, the dynamics exhibit a significant nonlinear internal magnetospheric response that may be related to increased solar wind speed.

  3. Tool use ability depends on understanding of functional dynamics and not specific joint contribution profiles

    Parry, Ross; Dietrich, Gilles; Bril, Blandine

    2014-01-01

    Researchers in cognitive neuroscience have become increasingly interested in how different aspects of tool use are integrated and represented by the brain. Comparatively less attention has been directed toward tool use actions themselves and how effective tool use behaviors are coordinated. In response, we take this opportunity to consider the mechanical principles of tool use actions and their relationship to motor learning. Using kinematic analysis, we examine both functional dynamics and joint contribution profiles of subjects with different levels of experience in a primordial percussive task. Our results show that the ability to successfully produce stone flakes using the Oldowan method did not correspond with any particular joint contribution profile. Rather, expertise in this tool use action was principally associated with the subject's ability to regulate the functional parameters that define the task itself. PMID:24795669

  4. Radial dependence of line profile variability in seven O9--B0.5 stars

    Martins, F; Hillier, D J; Donati, J -F; Bouret, J -C

    2014-01-01

    Massive stars show a variety of spectral variability: presence of discrete absorption components in UV P-Cygni profiles, optical line profile variability, X-ray variability, radial velocity modulations. Our goal is to study the spectral variability of single OB stars to better understand the relation between photospheric and wind variability. For that, we rely on high spectral resolution, high signal-to-noise ratio optical spectra collected with the spectrograph NARVAL on the Telescope Bernard Lyot at Pic du Midi. We investigate the variability of twelve spectral lines by means of the Temporal Variance Spectrum (TVS). The selected lines probe the radial structure of the atmosphere, from the photosphere to the outer wind. We also perform a spectroscopic analysis with atmosphere models to derive the stellar and wind properties, and to constrain the formation region of the selected lines. We show that variability is observed in the wind lines of all bright giants and supergiants, on a daily timescale. Lines form...

  5. Direct and two-step activity-based profiling of proteases and glycosidases

    Willems, Lianne Irene

    2014-01-01

    Activity-based protein profiling provides a powerful approach for the monitoring of active enzyme populations in complex biological samples by making use of activity-based probes (ABPs), chemical probes that are designed to bind specifically to the active site of an enzyme (family). The research described in this thesis concerns two main topics. First, new techniques are developed for the two-step labeling of enzymatic activity, a strategy that involves the targeting of enzymes with an ABP fo...

  6. Antibiotic Resistance Profiles and Quorum Sensing-Dependent Virulence Factors in Clinical Isolates of Pseudomonas Aeruginosa

    Wang, Huafu; Tu, Faping; Gui, Zhihong; Lu, Xianghong; Chu, Weihua

    2013-01-01

    Pseudomonas aeruginosa produces multiple virulence factors that have been associated with quorum sensing. The aim of this study was to evaluate the prevalence of drug resistant profiles and quorum sensing related virulence factors. Pseudomonas aeruginosa were collected from different patients hospitalized in China, the isolates were tested for their susceptibility to different common antimicrobial drugs and detected QS-related virulence factors. We identified 170 isolates displaying impaired ...

  7. Gene expression profiling of sex differences in HIF1-dependent adaptive cardiac responses to chronic hypoxia

    Bohuslavová, Romana; Kolář, František; Kuthanová, Lada; Neckář, Jan; Tichopád, Aleš; Pavlínková, Gabriela

    2010-01-01

    Roč. 109, č. 4 (2010), s. 1195-1202. ISSN 8750-7587 R&D Projects: GA ČR GA301/09/0117 Institutional research plan: CEZ:AV0Z50520701; CEZ:AV0Z50110509 Keywords : Hypoxia inducible factor 1 alpha * hypoxia * gene expression profiling Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.232, year: 2010

  8. SOMATOTYPE PROFILES AND CHANGES DEPENDING ON TREADMILL EXERCISE IN CHILDREN WITH CEREBRAL PALSY

    Nazmi; Betül; Hanife; Mustafa

    2014-01-01

    Objective. The postponement of the brain development as a result of brain lesion causes some functional inabilities affecting the whole body of the children with cerebral palsy compared to their peers. In this study, it was aimed to investigate the effects of the treadmill exercise on somatotype profiles and some variables in disabled children diagnosed with cerebral palsy. Methods. The subjects of the study were 37 children with cerebral palsy whose ages range from 7 to 15 and they were t...

  9. ANTIOXIDANT ACTIVITIES AND PHENOLIC PROFILE OF SIX MOROCCAN SELECTED HERBS

    Madiha Bichra

    2013-02-01

    Full Text Available The present work evaluated the antioxidant capacity of six plants commonly used in traditional Moroccan medicine. The antioxidant capacity was estimated by DPPH test, ferrous ion chelating activity and ABTS test. As results, the highest antioxidant activities were found in Mentha suaveolens, Salvia officinalis and Mentha viridis. Different species showed significant differences in their total phenolic content (TPC. The highest level of phenolics was found in Salvia officinalis and the lowest in Pelargonium roseum. Linear correlation was found between TPC, especially the non-flavonoid content (NFC and the antioxidant activity. Qualitative and quantitative analyzes of major phenolics by reverse-phase high-performance liquid chromatography (RP-HPLC were also performed. On the basis of the obtained results, these studied medicinal herbs were found to serve as a potential source of natural antioxidants due to their richness in phenolic compounds and marked antioxidant activity.

  10. ANTIOXIDANT ACTIVITIES AND PHENOLIC PROFILE OF SIX MOROCCAN SELECTED HERBS

    Madiha Bichra; Cherkaoui El-Modafar; Abdelilah El-Abbassi; Hafida Bouamama; Fatiha Benkhalti

    2013-01-01

    The present work evaluated the antioxidant capacity of six plants commonly used in traditional Moroccan medicine. The antioxidant capacity was estimated by DPPH test, ferrous ion chelating activity and ABTS test. As results, the highest antioxidant activities were found in Mentha suaveolens, Salvia officinalis and Mentha viridis. Different species showed significant differences in their total phenolic content (TPC). The highest level of phenolics was found in Salvia officinalis and the lowest...

  11. Distinct BOLD activation profiles following central and peripheral oxytocin administration in awake rats

    Craig F Ferris

    2015-09-01

    Full Text Available A growing body of literature has suggested that intranasal oxytocin (OT or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain-barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level dependent (BOLD signal intensity in response to peripheral OT injections (0.1, 0.5 or 2.5 mg/kg during functional magnetic resonance (fMRI in awake rats imaged at 7.0 tesla. These data were compared to OT (1ug/5 µl given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

  12. Profile of Executive and Memory Function Associated with Amphetamine and Opiate Dependence

    Ersche, Karen D.; Clark, Luke; London, Mervyn; Robbins, Trevor W.; Sahakian, Barbara J.

    2006-01-01

    Cognitive function was assessed in chronic drug users on neurocognitive measures of executive and memory function. Current amphetamine users were contrasted with current opiate users, and these two groups were compared with former users of these substances (abstinent for at least one year). Four groups of participants were recruited: amphetamine-dependent individuals, opiate-dependent individuals, former users of amphetamines, and/or opiates and healthy non-drug taking controls. Participants ...

  13. A novel approach for assuring and following inoculum activity during kefir grains growth studies: application of dynamic pH profiles:

    Tramšek, Marko; Goršek, Andreja

    2007-01-01

    The profiles of kefir grains growth curves strongly depend on bioprocess conditions and inoculum viability. Therefore, accurate growth curve studies require the use of optimally active kefir grains as inoculum. Accordingly, the main objective of our study was experimental optimization of classic kefir grains activation procedure and afterwards, comparison among growth curves of differently activated kefir grains. For this purpose some experiments were initially performed in computer-controlle...

  14. Mercury (Hg) in meteorites: variations in abundance, thermal release profile, mass-dependent and mass-independent isotopic fractionation

    Meier, Matthias M M; Marty, Bernard

    2016-01-01

    We have measured the concentration, isotopic composition and thermal release profiles of Mercury (Hg) in a suite of meteorites, including both chondrites and achondrites. We find large variations in Hg concentration between different meteorites (ca. 10 ppb to 14'000 ppb), with the highest concentration orders of magnitude above the expected bulk solar system silicates value. From the presence of several different Hg carrier phases in thermal release profiles (150 to 650 {\\deg}C), we argue that these variations are unlikely to be mainly due to terrestrial contamination. The Hg abundance of meteorites shows no correlation with petrographic type, or mass-dependent fractionation of Hg isotopes. Most carbonaceous chondrites show mass-independent enrichments in the odd-numbered isotopes 199Hg and 201Hg. We show that the enrichments are not nucleosynthetic, as we do not find corresponding nucleosynthetic deficits of 196Hg. Instead, they can partially be explained by Hg evaporation and redeposition during heating of ...

  15. Dependence of CIT [Compact Ignition Tokamak] PF [poloidal field] coil currents on profile and shape parameters using the Control Matrix

    The plasma shaping flexibility of the Compact Ignition Tokamak (CIT) poloidal field (PF) coil set is demonstrated through MHD equilibrium calculations of optimal PF coil current distributions and their variation with poloidal beta, internal inductance, plasma 95% elongation, and 95% triangularity. Calculations of the magnetic stored energy are used to compare solutions associated with various plasma parameters. The Control Matrix (CM) equilibrium code, together with the nonlinear equation and numerical optimization software packages HYBRD, and VMCON, respectively, are used to find equilibrium coil current distributions for fixed divertor geometry, volt-seconds, and plasma profiles in order to isolate the dependence on individual parameters. A reference equilibrium and coil current distribution are chosen, and correction currents dI are determined using the CM equilibrium method to obtain other specified plasma shapes. The reference equilibrium is the κ = 2 divertor at beginning of flattop (BOFT) with a minimum stored energy solution for the coil current distribution. The pressure profile function is fixed

  16. Kinks in experimental diffusion profiles of a dissolving semi-crystalline polymer explained by a concentration-dependent diffusion coefficient.

    Hermes, Helen E; Sitta, Christoph E; Schillinger, Burkhard; Löwen, Hartmut; Egelhaaf, Stefan U

    2015-06-28

    The dissolution of polyethylene oxide (PEO) tablets in water has been followed in situ by neutron radiography. When in contact with water, the crystalline phase of semi-crystalline PEO melts once a certain water content is attained. Polymer concentration profiles obtained from the neutron transmission images exhibited a pronounced kink which corresponds to a sharp front in the images and which is related to the melting transition. Sharp diffusion fronts and phase transitions are often linked to non-Fickian behaviour. However, by considering the time evolution of the complete concentration profiles in detail it is shown that the dissolution process can be explained using Fickian diffusion equations with a concentration-dependent diffusion coefficient. PMID:26018995

  17. Physical activity and physical fitness profiles of South African women

    Smit, Madelein; Strydom, Gert Lukas; Wilders, Cilas Jacobus

    2011-01-01

    The purpose of this study was to determine the leisure time physical activity (LTPA) participation and physical fitness (PF) levels of South African women of the various ethnic groups. Individuals between the ages of 30 and 60 years (=41.0; ±=4.6) who were part of a cross-sectional non-randomized availability population who voluntarily participated, were used in this study. The group that formed part of the physical activity survey included 3273 subjects (Asian =262; black=1357; coloured=239;...

  18. Cre-dependent DNA recombination activates a STING-dependent innate immune response.

    Pépin, Geneviève; Ferrand, Jonathan; Höning, Klara; Jayasekara, W Samantha N; Cain, Jason E; Behlke, Mark A; Gough, Daniel J; G Williams, Bryan R; Hornung, Veit; Gantier, Michael P

    2016-06-20

    Gene-recombinase technologies, such as Cre/loxP-mediated DNA recombination, are important tools in the study of gene function, but have potential side effects due to damaging activity on DNA. Here we show that DNA recombination by Cre instigates a robust antiviral response in mammalian cells, independent of legitimate loxP recombination. This is due to the recruitment of the cytosolic DNA sensor STING, concurrent with Cre-dependent DNA damage and the accumulation of cytoplasmic DNA. Importantly, we establish a direct interplay between this antiviral response and cell-cell interactions, indicating that low cell densities in vitro could be useful to help mitigate these effects of Cre. Taking into account the wide range of interferon stimulated genes that may be induced by the STING pathway, these results have broad implications in fields such as immunology, cancer biology, metabolism and stem cell research. Further, this study sets a precedent in the field of gene-engineering, possibly applicable to other enzymatic-based genome editing technologies. PMID:27166376

  19. Cre-dependent DNA recombination activates a STING-dependent innate immune response

    Pépin, Geneviève; Ferrand, Jonathan; Höning, Klara; Jayasekara, W. Samantha N.; Cain, Jason E.; Behlke, Mark A.; Gough, Daniel J.; G. Williams, Bryan R.; Hornung, Veit; Gantier, Michael P.

    2016-01-01

    Gene-recombinase technologies, such as Cre/loxP-mediated DNA recombination, are important tools in the study of gene function, but have potential side effects due to damaging activity on DNA. Here we show that DNA recombination by Cre instigates a robust antiviral response in mammalian cells, independent of legitimate loxP recombination. This is due to the recruitment of the cytosolic DNA sensor STING, concurrent with Cre-dependent DNA damage and the accumulation of cytoplasmic DNA. Importantly, we establish a direct interplay between this antiviral response and cell–cell interactions, indicating that low cell densities in vitro could be useful to help mitigate these effects of Cre. Taking into account the wide range of interferon stimulated genes that may be induced by the STING pathway, these results have broad implications in fields such as immunology, cancer biology, metabolism and stem cell research. Further, this study sets a precedent in the field of gene-engineering, possibly applicable to other enzymatic-based genome editing technologies. PMID:27166376

  20. Prediction of Process-Induced Distortions in L-Shaped Composite Profiles Using Path-Dependent Constitutive Law

    Ding, Anxin; Li, Shuxin; Wang, Jihui; Ni, Aiqing; Sun, Liangliang; Chang, Lei

    2016-05-01

    In this paper, the corner spring-in angles of AS4/8552 L-shaped composite profiles with different thicknesses are predicted using path-dependent constitutive law with the consideration of material properties variation due to phase change during curing. The prediction accuracy mainly depends on the properties in the rubbery and glassy states obtained by homogenization method rather than experimental measurements. Both analytical and finite element (FE) homogenization methods are applied to predict the overall properties of AS4/8552 composite. The effect of fiber volume fraction on the properties is investigated for both rubbery and glassy states using both methods. And the predicted results are compared with experimental measurements for the glassy state. Good agreement is achieved between the predicted results and available experimental data, showing the reliability of the homogenization method. Furthermore, the corner spring-in angles of L-shaped composite profiles are measured experimentally and the reliability of path-dependent constitutive law is validated as well as the properties prediction by FE homogenization method.

  1. The clinical and demographic profile of male patients with alcohol dependence syndrome

    M Pramod Kumar Reddy

    2014-01-01

    Full Text Available Aims: To study the demographic factors associated with alcohol dependence syndrome so that the problems of alcohol related co morbidities can be prevented with appropriate preventive measures. Materials and Methods: The study was conducted in De-Addiction Clinic of the Department of Psychiatry, Mamata Medical College, Khammam, Andhra Pradesh from July 2008 to February 2009. Patient who fulfills criteria for alcohol dependence, according to diagnostic and statistical manual of mental disorders, fourth edition were included. Results: Mean age (standard deviation at first drink was 18.93 (3.81 years and at onset of Alcohol dependence was 28.28 (6.55 years. The most common reason being given by the patients was financial strain (70% of the patients due to alcohol use and its consequences. Educational qualification of 12th standard or above was seen only in 7.5%. Alcohol dependence syndrome was more common in unemployed, unskilled and semi-skilled patients. Majority of patients (80% belonged to lower socio-economic class. Conclusion: Alcohol dependence syndrome and its related co morbidities can be minimized to a great extent if the educational and socio-economic standards are improved in countries like India where there is increase in alcohol consumption as a life style choice.

  2. Imaging Ligand-Dependent Activation of CXCR7

    Kathryn E. Luker

    2009-10-01

    Full Text Available Chemokine CXCL12 is proposed to promote multiple steps in growth of primary tumors and progression to metastatic disease in more than 20 different cancers. Functions of CXCL12 previously were believed to be controlled only by receptor CXCR4, but CXCR7 was recently identified as a second receptor for this chemokine. CXCR7 increases tumor formation and metastasis in mouse models, suggesting that this receptor may also be a key target for blocking effects of CXCL12 in cancer. To image activation of CXCR7 in intact cells and living mice, we tested the hypothesis that binding of chemokine ligands to CXCR7 recruits β-arrestins, a family of cytosolic adapter proteins that interact with many activated chemokine and related seven-transmembrane receptors. Using firefly luciferase protein fragment complementation, we established that chemokine ligands CXCL12 and CXCL11 significantly increase association of CXCR7 and β-arrestins with preferential interaction of the receptor with β-arrestin 2. The magnitude of interactions between CXCR7 and β-arrestin 2 increased over time after treatment with ligands, contrasting with transient association of β-arrestin 2 and CXCR4. β-Arrestin 2 increased uptake of CXCL12 in cells expressing CXCR7, emphasizing the functional relevance of the interaction between CXCR7 and β-arrestin 2. In an orthotopic xenograft model of human breast cancer, we used bioluminescence imaging to quantify changes in the association of CXCR7 and β-arrestin 2. These studies demonstrate ligand-dependent interactions of CXCR7 with β-arrestin 2 that promote accumulation of chemokines and establish an imaging assay for the dynamic regulation of CXCR7 by chemokines and candidate therapeutic agents in cell-based assays and living mice.

  3. Polyphenolic Profile, Antioxidant and Anti-Inflammatory Activity of Eastern Teaberry (Gaultheria procumbens L.) Leaf Extracts.

    Michel, Piotr; Dobrowolska, Anna; Kicel, Agnieszka; Owczarek, Aleksandra; Bazylko, Agnieszka; Granica, Sebastian; Piwowarski, Jakub P; Olszewska, Monika A

    2014-01-01

    Dry leaf extracts of eastern teaberry (Gaultheria procumbens L.) were evaluated as a source of bioactive phytocompounds through systematic activity testing and phytochemical profiling. The antioxidant efficiency was tested using five complementary in vitro models (DPPH; FRAP; linoleic acid (LA) peroxidation assay; O2•- and H2O2 scavenging tests) in parallel with standard antioxidants. The 75% methanol extract and its diethyl ether, ethyl acetate (EAF), n-butanol and water fractions exhibited the dose-dependent responses in all assays, with the highest capacities found for EAF (DPPH EC50 = 2.9 μg/mL; FRAP = 12.8 mmol Fe2+/g; IC50 for LA-peroxidation = 123.9 μg/mL; O2•- SC50 = 3.9 μg/mL; H2O2 SC50 = 7.2 μg/mL). The EAF had also the highest anti-inflammatory activity in the inhibition tests of lipoxygenase and hyaluronidase (60.14% and 21.83% effects, respectively, at the concentration of 100 μg/mL). Activity parameters of the extracts correlated strongly with the levels of total phenolics (72.4-270.7 mg GAE/g), procyanidins, and phenolic acids, whereas for flavonoids only moderate effects were observed. Comprehensive UHPLC-PDA-ESI-MS3 and HPLC-PDA studies led to the identification of 35 polyphenols with a procyanidin A-type trimer, quercetin 3-O-glucuronide, isomers of caffeoylquinic acids, and (‒)-epicatechin being the dominant components. Significant activity levels, high phenolic contents and high extraction yields (39.4%-42.5% DW for defatted and crude methanol extracts, respectively) indicate the value of eastern teaberry leaves as bioactive products. PMID:25493634

  4. Polyphenolic Profile, Antioxidant and Anti-Inflammatory Activity of Eastern Teaberry (Gaultheria procumbens L. Leaf Extracts

    Piotr Michel

    2014-12-01

    Full Text Available Dry leaf extracts of eastern teaberry (Gaultheria procumbens L. were evaluated as a source of bioactive phytocompounds through systematic activity testing and phytochemical profiling. The antioxidant efficiency was tested using five complementary in vitro models (DPPH; FRAP; linoleic acid (LA peroxidation assay; O2•− and H2O2 scavenging tests in parallel with standard antioxidants. The 75% methanol extract and its diethyl ether, ethyl acetate (EAF, n-butanol and water fractions exhibited the dose-dependent responses in all assays, with the highest capacities found for EAF (DPPH EC50 = 2.9 μg/mL; FRAP = 12.8 mmol Fe2+/g; IC50 for LA-peroxidation = 123.9 μg/mL; O2•− SC50 = 3.9 μg/mL; H2O2 SC50 = 7.2 μg/mL. The EAF had also the highest anti-inflammatory activity in the inhibition tests of lipoxygenase and hyaluronidase (60.14% and 21.83% effects, respectively, at the concentration of 100 μg/mL. Activity parameters of the extracts correlated strongly with the levels of total phenolics (72.4–270.7 mg GAE/g, procyanidins, and phenolic acids, whereas for flavonoids only moderate effects were observed. Comprehensive UHPLC-PDA-ESI-MS3 and HPLC-PDA studies led to the identification of 35 polyphenols with a procyanidin A-type trimer, quercetin 3-O-glucuronide, isomers of caffeoylquinic acids, and (‒-epicatechin being the dominant components. Significant activity levels, high phenolic contents and high extraction yields (39.4%–42.5% DW for defatted and crude methanol extracts, respectively indicate the value of eastern teaberry leaves as bioactive products.

  5. Chilean Prosopis Mesocarp Flour: Phenolic Profiling and Antioxidant Activity

    Guillermo Schmeda-Hirschmann

    2015-04-01

    Full Text Available In South America, the mesocarp flour of Prosopis species plays a prominent role as a food resource in arid areas. The aim of this work was the characterization of the phenolic antioxidants occurring in the pod mesocarp flour of Chilean Prosopis. Samples were collected in the Copiapo, Huasco and Elqui valleys from the north of Chile. The samples of P. chilensis flour exhibited a total phenolic content ranging between 0.82–2.57 g gallic acid equivalents/100 g fresh flour weight. The highest antioxidant activity, measured by the DPPH assay, was observed for samples from the Huasco valley. HPLC-MS/MS analysis allowed the tentative identification of eight anthocyanins and 13 phenolic compounds including flavonol glycosides, C-glycosyl flavones and ellagic acid derivatives. The antioxidant activity and the phenolic composition in the flour suggest that this ancient South American resource may have potential as a functional food.

  6. Chilean prosopis mesocarp flour: phenolic profiling and antioxidant activity.

    Schmeda-Hirschmann, Guillermo; Quispe, Cristina; Soriano, Maria Del Pilar C; Theoduloz, Cristina; Jiménez-Aspée, Felipe; Pérez, Maria Jorgelina; Cuello, Ana Soledad; Isla, Maria Inés

    2015-01-01

    In South America, the mesocarp flour of Prosopis species plays a prominent role as a food resource in arid areas. The aim of this work was the characterization of the phenolic antioxidants occurring in the pod mesocarp flour of Chilean Prosopis. Samples were collected in the Copiapo, Huasco and Elqui valleys from the north of Chile. The samples of P. chilensis flour exhibited a total phenolic content ranging between 0.82-2.57 g gallic acid equivalents/100 g fresh flour weight. The highest antioxidant activity, measured by the DPPH assay, was observed for samples from the Huasco valley. HPLC-MS/MS analysis allowed the tentative identification of eight anthocyanins and 13 phenolic compounds including flavonol glycosides, C-glycosyl flavones and ellagic acid derivatives. The antioxidant activity and the phenolic composition in the flour suggest that this ancient South American resource may have potential as a functional food. PMID:25898415

  7. Molecular Profiling of Activated Neurons by Phosphorylated Ribosome Capture

    Knight, Zachary A.; Tan, Keith; Birsoy, Kivanc; Schmidt, Sarah; Garrison, Jennifer L.; Wysocki, Robert W.; Emiliano, Ana; Ekstrand, Mats I.; Friedman, Jeffrey M.

    2012-01-01

    The mammalian brain is composed of thousands of interacting neural cell types. Systematic approaches to establish the molecular identity of functional populations of neurons would advance our understanding of neural mechanisms controlling behavior. Here, we show that ribosomal protein S6, a structural component of the ribosome, becomes phosphorylated in neurons activated by a wide range of stimuli. We show that these phosphorylated ribosomes can be captured from mouse brain homogenates, there...

  8. Chemicals profiling and antioxidants activities of Acacia seeds

    Ennajeh, Imen; Laajel, Mejda; Khouja, Mohamed-Larbi; Ferchichi, Ali; Nasri, Nizar

    2011-01-01

    This study reported investigations on phytochemical screening and antioxidants activities of seeds from seven Acacia species. Storage proteins and mineral contents were determined. The seed extracts of Acacia species were evaluated for their total phenols, flavonoids, carotenoids contents and total antioxidant capacity assessed by 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. Total protein content ranged from 99.49 (Acacia cyclops...

  9. Sympathetic Activation Induces Skeletal Fgf23 Expression in a Circadian Rhythm-dependent Manner*

    Kawai, Masanobu; Kinoshita, Saori; Shimba, Shigeki; Ozono, Keiichi; Michigami, Toshimi

    2014-01-01

    The circadian clock network is well known to link food intake and metabolic outputs. Phosphorus is a pivotal nutritional factor involved in energy and skeletal metabolisms and possesses a circadian profile in the circulation; however, the precise mechanisms whereby phosphate metabolism is regulated by the circadian clock network remain largely unknown. Because sympathetic tone, which displays a circadian profile, is activated by food intake, we tested the hypothesis that phosphate metabolism was regulated by the circadian clock network through the modification of food intake-associated sympathetic activation. Skeletal Fgf23 expression showed higher expression during the dark phase (DP) associated with elevated circulating FGF23 levels and enhanced phosphate excretion in the urine. The peaks in skeletal Fgf23 expression and urine epinephrine levels, a marker for sympathetic tone, shifted from DP to the light phase (LP) when mice were fed during LP. Interestingly, β-adrenergic agonist, isoproterenol (ISO), induced skeletal Fgf23 expression when administered at ZT12, but this was not observed in Bmal1-deficient mice. In vitro reporter assays revealed that ISO trans-activated Fgf23 promoter through a cAMP responsive element in osteoblastic UMR-106 cells. The mechanism of circadian regulation of Fgf23 induction by ISO in vivo was partly explained by the suppressive effect of Cryptochrome1 (Cry1) on ISO signaling. These results indicate that the regulation of skeletal Fgf23 expression by sympathetic activity is dependent on the circadian clock system and may shed light on new regulatory networks of FGF23 that could be important for understanding the physiology of phosphate metabolism. PMID:24302726

  10. DCC constrains tumour progression via its dependence receptor activity.

    Castets, Marie; Broutier, Laura; Molin, Yann; Brevet, Marie; Chazot, Guillaume; Gadot, Nicolas; Paquet, Armelle; Mazelin, Laetitia; Jarrosson-Wuilleme, Loraine; Scoazec, Jean-Yves; Bernet, Agnès; Mehlen, Patrick

    2012-02-23

    The role of deleted in colorectal carcinoma (DCC) as a tumour suppressor has been a matter of debate for the past 15 years. DCC gene expression is lost or markedly reduced in the majority of advanced colorectal cancers and, by functioning as a dependence receptor, DCC has been shown to induce apoptosis unless engaged by its ligand, netrin-1 (ref. 2). However, so far no animal model has supported the view that the DCC loss-of-function is causally implicated as predisposing to aggressive cancer development. To investigate the role of DCC-induced apoptosis in the control of tumour progression, here we created a mouse model in which the pro-apoptotic activity of DCC is genetically silenced. Although the loss of DCC-induced apoptosis in this mouse model is not associated with a major disorganization of the intestines, it leads to spontaneous intestinal neoplasia at a relatively low frequency. Loss of DCC-induced apoptosis is also associated with an increase in the number and aggressiveness of intestinal tumours in a predisposing APC mutant context, resulting in the development of highly invasive adenocarcinomas. These results demonstrate that DCC functions as a tumour suppressor via its ability to trigger tumour cell apoptosis. PMID:22158121

  11. Analysis of whey protein hydrolysates: peptide profile and ACE inhibitory activity

    Marialice Pinto Coelho Silvestre

    2012-12-01

    Full Text Available The aim of this study was to prepare enzymatic hydrolysates from whey protein concentrate with a nutritionally adequate peptide profile and the ability to inhibit angiotensin-converting enzyme (ACE activity. The effects of the type of enzyme used (pancreatin or papain, the enzyme:substrate ratio (E:S ratio=0.5:100, 1:100, 2:100 and 3:100 and the use of ultrafiltration (UF were investigated. The fractionation of peptides was performed by size-exclusion-HPLC, and the quantification of the components of the chromatographic fractions was carried out by a rapid Corrected Fraction Area method. The ACE inhibitory activity (ACE-IA was determined by Reverse Phase-HPLC. All parameters tested affected both the peptide profile and the ACE-IA. The best peptide profile was achieved for the hydrolysates obtained with papain, whereas pancreatin was more advantageous in terms of ACE-IA. The beneficial effect of using a lower E:S ratio on the peptide profile and ACE-IA was observed for both enzymes depending on the conditions used to prepare the hydrolysates. The beneficial effect of not using UF on the peptide profile was observed in some cases for pancreatin and papain. However, the absence of UF yielded greater ACE-IA only when using papain.O objetivo deste estudo foi preparar hidrolisados enzimáticos do concentrado proteico do soro de leite com perfil peptídico nutricionalmente adequado e com capacidade para inibir a atividade da enzima conversora da angiotensina (ECA. Os efeitos do tipo de enzima usado (pancreatina ou papaína, da relação enzima:substrato (E:S=0,5:100, 1:100, 2:100 e 3:100 e do uso da ultrafiltração (UF foram investigados. O fracionamento dos peptídeos foi feito por CLAE de exclusão molecular e a quantificação dos componentes das frações cromatográficas foi realizada pelo método da Área Corrigida da Fração. A atividade inibitória da ECA (AI-ECA foi determinada por CLAE de fase reversa. Todos os parâmetros testados afetaram

  12. Active flow control for reduction of fluctuating aerodynamic forces of a blunt trailing edge profiled body

    Naghib-Lahouti, Arash, E-mail: anaghibl@uwo.c [Boundary Layer Wind Tunnel Laboratory, University of Western Ontario, London, Ontario, N6A 5B9 (Canada); Hangan, Horia [Boundary Layer Wind Tunnel Laboratory, University of Western Ontario, London, Ontario, N6A 5B9 (Canada)

    2010-12-15

    Vortex shedding in the wake of two-dimensional bluff bodies is usually accompanied by three dimensional instabilities. These instabilities result in streamwise and vertical vorticity components which occur at a certain spanwise wavelength. The spanwise wavelength of the instabilities ({lambda}{sub Z}) depends on several parameters, including profile geometry and Reynolds number. The objective of the present work is to study the three dimensional wake instabilities for a blunt trailing edge profiled body, comprised of an elliptical leading edge and a rectangular trailing edge, and to manipulate these instabilities to control the aerodynamic forces. Results of numerical simulations of flow around the body at Re(d) = 400, 600, and 1000, as well as planar Laser Induced Fluorescence (LIF) flow visualizations at Re(d) = 600 and 1000 are analyzed to determine the wake vorticity structure and {lambda}{sub Z}. Based on the findings of these analyses, an active flow control mechanism for attenuation of the fluctuating aerodynamic forces on the body is proposed. The flow control mechanism is comprised of a series of trailing edge injection ports distributed across the span, with a spacing equal to {lambda}{sub Z}. Injection of a secondary flow leads to amplification of the three dimensional instabilities and disorganization of the von Karman vortex street. Numerical simulations indicate that the flow control mechanism can attenuate the fluctuating aerodynamic forces at lower Reynolds numbers (Re(d) = 400 and 600) where {lambda}{sub Z} is constant in time. However, the control mechanism loses its effectiveness at Re(d) = 1000, due to the temporal variations of {lambda}{sub Z}.

  13. Surface Activity of Humic Acids Depending on Their Origin and Humification Degree

    Klaviņš Māris

    2014-07-01

    Full Text Available Humic substances are able to reduce the surface tension of their solutions and thus can act as surface-active substances in the natural environment, which may have industrial application. The ability to influence the surface tension of humic acid solutions depends on the origin of the humic acids. The objective of this study was comparison of the ability of humic acids of different origin (soil, water, peat, lignite etc. to influence the surface tension of their solutions, and identification of the structural characteristics of peat humic acids that determine their surfactant properties. Industrially produced humic materials demonstrated no or insignificant impact on the surface tension of their solutions. However, humic acids isolated from peat had significant impact of the surface tension of their solutions, acting as weak surfactants. The surface tension of humic acid solutions decreased with increasing concentration, and depended on solution pH. Using a well-characterised bog profile, the ability to influence the surface tension of peat humic acids was shown to depend on age and humification degree. With increase of the humification degree and age, molecular complexity of humic acids and their ability to influence surface tension decreased; but nevertheless, the impact of the biological precursor (peat-forming bryophytes and plants could be identified.

  14. Enzyme activity profiles during fruit development in tomato cultivars and Solanum pennellii

    Steinhauser, Marie-Caroline; Steinhauser, Dirk; Koehl, Karin; Carrari, Fernando; Gibon, Yves; Fernie, Alisdair R.; Stitt, Mark

    2010-01-01

    Enzymes interact to generate metabolic networks. The activities of more than 22 enzymes from central metabolism were profiled during the development of fruit of the modern tomato cultivar Solanum lycopersicum 'M82' and its wild relative Solanum pennellii (LA0716). In S. pennellii, the mature fruit remains green and contains lower sugar and higher organic acid levels. These genotypes are the parents of a widely used near introgression line population. Enzymes were also profiled in a second cul...

  15. HPLC-based activity profiling of Angelica pubescens roots for new positive GABAA receptor modulators in Xenopus oocytes.

    Zaugg, Janine; Eickmeier, Eva; Rueda, Diana C; Hering, Steffen; Hamburger, Matthias

    2011-04-01

    A petroleum ether extract of the traditional Chinese herbal drug Duhuo (roots of Angelica pubescens Maxim. f. biserrata Shan et Yuan), showed significant activity in a functional two-microelectrode voltage clamp assay with Xenopus oocytes which expressed recombinant γ-aminobutyric acid type A (GABA(A)) receptors of the subtype α(1)β(2)γ(2S). HPLC-based activity profiling of the active extract revealed six compounds responsible for the GABA(A) receptor modulating activity. They were identified by microprobe NMR and high resolution mass spectrometry as columbianetin acetate (1), imperatorin (3), cnidilin (4), osthol (5), and columbianedin (6). In concentration-dependent experiments, osthol and cnidilin showed the highest potentiation of the GABA induced chloride current (273.6%±39.4% and 204.5%±33.2%, respectively at 300 μM). Bisabolangelone (2) only showed minor activity at the GABA(A) receptor. The example demonstrates that HPLC-based activity profiling is a simple and efficient method to rapidly identify GABA(A) receptor modulators in a bioactive plant extract. PMID:21147202

  16. Phenolic Profiles and Antioxidant Activity of Lotus Root Varieties

    Yang Yi

    2016-06-01

    Full Text Available Lotus root attracts increasing attention mainly because of its phenolic compounds known as natural antioxidants. Its thirteen varieties were systematically analyzed on the content, distribution, composition and antioxidant activity of phenolic compounds for a better understanding of this aquatic vegetable. The respective mean contents of total phenolics in their flesh, peel and nodes were 1.81, 4.30 and 7.35 mg gallic acid equivalents (GAE/g fresh weight (FW, and those of total flavonoids were 3.35, 7.69 and 15.58 mg rutin equivalents/g FW. The phenolic composition determined by a high-performance liquid chromatography method varied significantly among varieties and parts. The phenolics of flesh were mainly composed of gallocatechin and catechin; those of peel and node were mainly composed of gallocatechin, gallic acid, catechin and epicatechin. The antioxidant activities of phenolic extracts in increasing order were flesh, peel and node; their mean concentrations for 50% inhibition of 2,2-diphenyl-1-picrylhydrazyl radical were 46.00, 26.43 and 21.72 µg GAE/mL, and their mean values representing ferric reducing antioxidant power were 75.91, 87.66 and 100.43 µg Trolox equivalents/100 µg GAE, respectively. “Zoumayang”, “Baheou”, “No. 5 elian” and “Guixi Fuou” were the hierarchically clustered varieties with relatively higher phenolic content and stronger antioxidant activity as compared with the others. Especially, their nodes and peels are promising sources of antioxidants for human nutrition.

  17. Lipid profiling by multiple precursor and neutral loss scanning driven by the data-dependent acquisition

    Schwudke, Dominik; Oegema, Jeffrey; Burton, Lyle; Entchev, Eugeni; Hannich, J Thomas; Ejsing, Christer S.; Kurzchalia, Teymuras; Shevchenko, Andrej

    2006-01-01

    Data-dependent acquisition of MS/MS spectra from lipid precursors enables to emulate the simultaneous acquisition of an unlimited number of precursor and neutral loss scans in a single analysis. This approach takes full advantage of rich fragment patterns in tandem mass spectra of lipids and...

  18. Green and roasted mate: phenolic profile and antioxidant activity

    EROL, Nihal Türkmen; Sari, Ferda; ÇALIKOĞLU, Eda; VELİOĞLU, Yakup Sedat

    2009-01-01

    Mate infusions have been recently and frequently used as dietary supplements because of their health effects to prevent atherosclerosis and coronary heart disease and to be antioxidant. The aim of this study was to determine phenolic compounds and antioxidant activities of green mate (GM) and roasted mate (RM) extracts and compare them with green tea (GT). Total polyphenol content of GM and RM extracts was found to be similar and to range from 237.20 to 438.50 mg gallic acid equivalent (GAE) ...

  19. Elite futsal refereeing: Activity profile and physiological demands

    Rebelo, António N.; Ascensão, António A.; Magalhães, José F.;

    2011-01-01

    the game. Endurance capacity was determined with the Yo-Yo IE2. The number of activity changes was as high as 1,395 ± 218 (±SD). Total distance covered, high-intensity running (HIR), sprinting (SPR), and sideways running were 5.89 ± 0.56, 0.96 ± 0.29, 0.09 ± 0.07, and 0.91 ± 0.46 km, respectively. The....... Considering the data obtained in the present study, the use of match-specific intermittent fitness tests to evaluate futsal referees seems to be required....

  20. Prevalence of human cell material: DNA and RNA profiling of public and private objects and after activity scenarios.

    van den Berge, M; Ozcanhan, G; Zijlstra, S; Lindenbergh, A; Sijen, T

    2016-03-01

    Especially when minute evidentiary traces are analysed, background cell material unrelated to the crime may contribute to detectable levels in the genetic analyses. To gain understanding on the composition of human cell material residing on surfaces contributing to background traces, we performed DNA and mRNA profiling on samplings of various items. Samples were selected by considering events contributing to cell material deposits in exemplary activities (e.g. dragging a person by the trouser ankles), and can be grouped as public objects, private samples, transfer-related samples and washing machine experiments. Results show that high DNA yields do not necessarily relate to an increased number of contributors or to the detection of other cell types than skin. Background cellular material may be found on any type of public or private item. When a major contributor can be deduced in DNA profiles from private items, this can be a different person than the owner of the item. Also when a specific activity is performed and the areas of physical contact are analysed, the "perpetrator" does not necessarily represent the major contributor in the STR profile. Washing machine experiments show that transfer and persistence during laundry is limited for DNA and cell type dependent for RNA. Skin conditions such as the presence of sebum or sweat can promote DNA transfer. Results of this study, which encompasses 549 samples, increase our understanding regarding the prevalence of human cell material in background and activity scenarios. PMID:26736139

  1. Radial dependence of line profile variability in seven O9-B0.5 stars

    Martins, F.; Marcolino, W.; Hillier, D. J.; Donati, J.-F.; Bouret, J.-C.

    2015-02-01

    Context. Massive stars show a variety of spectral variabilities: discrete absorption components in UV P-Cygni profiles, optical line profile variability, X-ray variability, and radial velocity modulations. Aims: Our goal is to study the spectral variability of single OB stars to better understand the relation between photospheric and wind variability. For that, we rely on high spectral resolution and on high signal-to-noise ratio optical spectra collected with the spectrograph NARVAL on the Télescope Bernard Lyot at Pic du Midi. Methods: We investigated the variability of twelve spectral lines by means of the temporal variance spectrum. The selected lines probe the radial structure of the atmosphere from the photosphere to the outer wind. We also performed a spectroscopic analysis with atmosphere models to derive the stellar and wind properties and to constrain the formation region of the selected lines. Results: We show that variability is observed in the wind lines of all bright giants and supergiants on a daily timescale. Lines formed in the photosphere are sometimes variable, sometimes not. The dwarf stars do not show any sign of variability. If variability is observed on a daily timescale, it can also (but not always) be observed on hourly timescales, albeit with lower amplitude. There is a very clear correlation between amplitude of the variability and fraction of the line formed in the wind. Strong anti-correlations between the different parts of the temporal variance spectrum are observed. Conclusions: Our results indicate that variability is stronger in lines formed in the wind. A link between photospheric and wind variability is not obvious from our study, since wind variability is observed regardless of the level of photospheric variability. Different photospheric lines also show different degrees of variability. Appendices are available in electronic form at http://www.aanda.org

  2. Sulphate-activated phosphorylase b: the pH-dependence of catalytic activity.

    Zographos, S E; Oikonomakos, N G; Dixon, H B; Griffin, W G; Johnson, L N; Leonidas, D D

    1995-09-01

    The pH-dependence of sulphate-activated phosphorylase b has been studied in the direction of glycogen synthesis. The bell-shaped curve of the pH-dependence of the catalytic constant for the AMP-activated enzyme showed pK values of 6.1 and 7.3, but the curve for the enzyme activated by 0.9 M ammonium sulphate showed a drop of activity on the acid side at much higher pH values. Its bell was centred at pH 7.8 but it was too narrow to be characterized by only two pK values. The narrowness of the curve could be explained by positive co-operativity, but not its unusually steep acid side. We suggest that the fall on the acid side is due to more than one hydronation (addition of H+). The points can be fitted by a curve with two de-activating hydronations and a de-activating dehydronation having identical titration pK values of 7.5, and hence molecular values of 7.0, 7.5 and 8.0. If both 0.9 M ammonium sulphate and 5 mM AMP are added, the bell is as broad as with AMP alone, but is somewhat raised in pH optimum. The results are discussed in the light of new structural data from crystallographic studies on binary complexes of the enzyme. PMID:7654195

  3. Testing the descriptive performance of the rank-dependent utility in the domain of health profiles

    Abell??n, Jos?? M.; Pinto, Jos?? Luis

    2001-01-01

    Expected utility theory (EUT) has been challenged as a descriptive theory in many contexts. The medical decision analysis context is not an exception. Several researchers have suggested that rank dependent utility theory (RDUT) may accurately describe how people evaluate alternative medical treatments. Recent research in this domain has addressed a relevant feature of RDU models - probability weighting - but to date no direct test of this theory has been made. This paper provides a test of th...

  4. Chromatogram Profiles and Cytotoxic Activity of Irradiated Mahkota Dewa (Phaleria Macrocarpa Scheff. Boerl Leaves

    E. Katrin1

    2011-04-01

    Full Text Available Gamma irradiation has been used by the industries for preservation of herbal medicine, but it has not been studied the effect of gamma irradiation on their efficacy, especially their bioactivity as anticancer substances. The purpose of this research was to study the effect of gamma irradiation on the mahkota dewa leaves which has been claimed to contain potent anticancer substances. Maceration of dried mahkota dewa leaves successively with n-hexane, ethyl acetate, and ethanol gave crude extracts which the ethyl acetate was the most cytotoxic extract against leukemia L1210 cells with an inhibition concentration fifty (IC50 value of 10.3 µg/ml. Further separation of ethyl acetate extract by column chromatograph gave 7 fractions, and fraction 2 showed the most cytotoxic fraction exhibited the most cytotoxic extract against leukemia L1210 cells with an IC50 value of 1.9 µg/ml. Since, the fraction 2 of ethyl acetate extract was the most potent fraction, the irradiated samples were treated with the same procedure as treatment of fraction 2 from control sample. Cytotoxic activity test of fractions 2 from irradiated samples showed that the cytotoxic activity decreased depending on increasing of irradiation dose. Gamma irradiation dose up to 7.5 kGy on mahkota dewa leaves could decreased the cytotoxic activity of fraction 2 as the most cytotoxic-potential fraction against leukemia L1210 cells, but decreasing the cytotoxic activity has not exceeded the limit of the fraction declared inactive. So that the irradiation dose up to 7.5 kGy can be used for decontamination of bacteria and fungus/yeast without eliminating the cytotoxic activity. Gamma irradiation also caused changes in the thin layer chromatograph (TLC spots and HPLC chromatograms profiles of fraction 2 which was the most cytotoxic fraction in ethyl acetate extract of mahkota dewa leaves against leukemia L1210 cells. One of the main peaks (peak 1 on HPLC chromatograms decreased with increasing

  5. Alkaloid profiling and anticholinesterase activity of South American Lycopodiaceae species.

    Konrath, Eduardo Luis; Ortega, María Gabriela; de Loreto Bordignon, Sérgio; Apel, Miriam Anders; Henriques, Amélia Teresinha; Cabrera, José Luis

    2013-02-01

    The alkaloid extracts of four Huperzia and one Lycopodiella species, from Brazilian habitats, were tested for their in vitro anticholinesterase activities. IC(50) values showed a potent acetylcholinesterase inhibition for H. reflexa (0.11 ± 0.05 μg/mL), followed by H. quadrifariata (2.0 ± 0.3 μg/mL), H. acerosa (5.5 ± 0.9 μg/mL), H. heterocarpon (25.6 ± 2.7 μg/mL) and L. cernua (42.6 ± 1.5 μg/mL). A lower inhibition of butyrylcholinesterase was observed for all species with the exception of H. heterocarpon (8.3 ± 0.9 μg/mL), whose alkaloid extract presented a selectivity for pseudocholinesterase. Moreover, the chemical study of the bioactive extracts performed by GC-MS, revealed the presence of a number of Lycopodium alkaloids belonging to the lycopodane, flabellidane and cernuane groups. Surprisingly, the potent acetylcholinesterase inhibitors huperzines A and B were not detected in the extracts, suggesting that other alkaloids may be responsible for such an effect. PMID:22117191

  6. A profile of the in vitro antitumor activity of lissoclinolide

    Lissoclinolide is a small non-nitrogenous lactone isolated from the marine ascidian Lissoclinum patella. Previous studies of lissoclinolide (isolated from a fungus and an actinomycete) have identified varying activity against both Gram-negative and Gram-positive bacteria. In this study, lissoclinolide was able to inhibit cell growth in various mammalian tumor lines at an average IC50 of 395 nM (determined by MTT conversion after 48-h treatment). Treatment of HCT 116 human colon tumor cells with 2.4 μM lissoclinolide resulted in a strong arrest in the G2/M phase of the cell cycle after 24-h exposure. A daughter cell line lacking p53 showed an identical response while there was a slight increase in cytotoxicity towards a p21 null cell line. Although treatment with 2.4 μM lissoclinolide did not result in apoptosis after 48 h, this arrest was not reversible when drug wash out was attempted. The mechanism of action does not appear to involve tubulin, ubiquitin-specific isopeptidases, p53 or p21. COMPARE analysis in the NCI 60 cell line tumor panel revealed a moderate selectivity towards colon tumor cell lines

  7. HCl and ClO in activated Arctic air; first retrieved vertical profiles from TELIS submillimetre limb spectra

    A. de Lange

    2012-02-01

    Full Text Available The first profile retrieval results of the Terahertz and submillimeter Limb Sounder (TELIS balloon instrument are presented. The spectra are recorded during a 13-h balloon flight on 24 January 2010 from Kiruna, Sweden. The TELIS instrument was mounted on the MIPAS-B2 gondola and shared this platform with the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS and the mini-Differential Optical Absorption Spectroscopy (mini-DOAS instruments. The flight took place within the Arctic vortex at an altitude of ≈34 km in chlorine activated air, and both active (ClO and inactive chlorine (HCl were measured over an altitude range of respectively ≈16–32 km and ≈10–32 km. In this altitude range, the increase of ClO concentration levels during sunrise has been recorded with a temporal resolution of one minute. During the daytime equilibrium, a maximum ClO level of 2.1 ± 0.3 ppbv has been observed at an altitude of 23.5 km. This equilibrium profile is validated against the ClO profile by the satellite instrument Microwave Limb Sounder (MLS aboard EOS Aura. HCl profiles have been determined from two different isotopes – H35Cl and H37Cl – and are also validated against MLS. The precision of all profiles is well below 0.01 ppbv and the overall accuracy is therefore governed by systematic effects. The total uncertainty of these effects is estimated to be maximal 0.3 ppbv for ClO around its peak value at 23.5 km during the daytime equilibrium, and for HCl it ranges from 0.05 to 0.4 ppbv, depending on altitude. In both cases the main uncertainty stems from a largely unknown non-linear response in the detector.

  8. THE SACCHARIDE PROFILE OF POLISH HONEYS DEPENDING ON THEIR BOTANICAL ORIGIN

    Zielińska S.

    2014-04-01

    Full Text Available Thirty honey samples (18 monofloral, 6 multifloral and 6 honeydew were collected directly from apiaries localized in the South-Eastern Poland. Monosaccharide profiles (glucose/fructose ratio in honey were examined by HPLC method with ELSD-detection. The results were compared with other parameters used in honey sugar analysis, i.e. a level of reducing sugars measured by Lane-Eynon, sugar extract (refractometric, specific rotation angle and glucose content determined with Reflectoquant® test (Merck. Moreover, some physicochemical parameters such as: water content, free acids and HMF content by White method were tested. The content of monosaccharides determined by HPLC (as sum of glucose and fructose and Lane-Eynon methods were compared (r=0.83 and changed from 68% in rape honey to 78% on average in goldenrod honey. All studied honeys showed the ratio of fructose/glucose above 1.5. The measurement of the specific optical rotation allowed to distinguish nectar (- and honeydew (+ honey, but due to the heterogeneity of the results, they could not be used for identification of the floral honeys. The results of reflectometric test for glucose level were positively correlated with values measured by HPLC method (r=0.73.

  9. Distribution of Metabolically Active Prokaryotes (Archaea and Bacteria) throughout the Profiles of Chernozem and Brown Semidesert Soil

    Semenov, M. V.; Manucharova, N. A.; Stepanov, A. L.

    2016-02-01

    The distribution of metabolically active cells of archaea and bacteria in the profiles of typical chernozems (Voronezh oblast) and brown semidesert soils (Astrakhan oblast) of natural and agricultural ecosystems was studied using the method of fluorescent in situ hybridization (FISH). The studied soils differed sharply in the microbial biomass and in the numbers of metabolically active cells of archaea and bacteria. The number of active bacterial cells was 3.5-7.0 times greater than that of archaea. In the arable chernozem, the numbers of active cells of archaea and bacteria were 2.6 and 1.5 times, respectively, lower than those in the chernozem under the shelterbelt. The agricultural use of the brown semidesert soil had little effect on the abundances of bacteria and archaea. The soil organic carbon content was the major factor controlling the numbers of metabolically active cells of both domains. However, the dependence of the abundance of bacteria on the organic matter content was more pronounced. The decrease in the organic carbon and total nitrogen contents down the soil profiles was accompanied by the decrease in the bacteria: archaea ratio attesting to a better adaptation of archaea to the permanent deficiency of carbon and nitrogen. The bacteria: archaea ratio can serve as an ecotrophic indicator of the state of soil microbial communities.

  10. Imatinib-dependent tyrosine phosphorylation profiling of Bcr-Abl-positive chronic myeloid leukemia cells

    Preisinger, C.; Schwarz, J. P.; Bleijerveld, O.B.; et al

    2012-01-01

    Bcr-Abl is the major cause and pathogenetic principle of chronic myeloid leukemia (CML). Bcr-Abl results from a chromosomal translocation that fuses the bcr and abl genes, thereby generating a constitutively active tyrosine kinase, which stimulates several signaling networks required for proliferation and survival. peer-reviewed

  11. Activity profile of the CA125 antigen towards human red blood cells

    Mitić N.

    2010-01-01

    Full Text Available Starting from the mucin nature of the CA125 antigen and conditions associated with high serum concentrations, this study is an attempt to gain insight into its activity profile towards human erythrocytes. Carcinomaassociated and pregnancy-associated CA125 antigens were tested in agglutination/aggregation, adhesion and hemolysis assays. The results obtained indicated that CA125 antigens increased agglutination/aggregation and inhibited erythrocyte adhesion, but differed in their effective concentrations. Galectin-1 slightly modulated the effects observed. CA125 antigens had no effect on hemolysis. The activity profile of the CA125 antigen towards erythrocytes may have biomedical consequences in different microenvironments in relevant physiological and pathophysiological conditions.

  12. SOMATOTYPE PROFILES AND CHANGES DEPENDING ON TREADMILL EXERCISE IN CHILDREN WITH CEREBRAL PALSY

    Nazmi

    2014-08-01

    Full Text Available Objective. The postponement of the brain development as a result of brain lesion causes some functional inabilities affecting the whole body of the children with cerebral palsy compared to their peers. In this study, it was aimed to investigate the effects of the treadmill exercise on somatotype profiles and some variables in disabled children diagnosed with cerebral palsy. Methods. The subjects of the study were 37 children with cerebral palsy whose ages range from 7 to 15 and they were taking regular physical therapy in a private education and rehabilitation center. The experimental group and the control group consists of 20 children (8 girls and 12 boys and 17 children (10 girls and 7 boys, respectively. The subjects of the experimental group were performed treadmill exercise under the supervision of a physical therapist twice a week for three months (totally 24 walking exercises while their treatments in the center were continuing. The initial and final speeds, duration of the exercise, the distance covered and the calories burnt were recorded and the somatotypical characteristics of the subjects were evaluated before and after the study. Results. It was encountered that the initial and final pace of the exercise, the duration of the use of the treadmill, the distance covered and the calories burnt increased significantly. No remarkable changes in the pulse rates were determined before and after the exercise. During the comparison of the experimental and control groups before and after the exercise, some noteworthy variations in ectomorphy and ponderal index were confirmed after the exercise even though no considerable differences in mesomorphy, endomorphy and body fat percentage were determined. Conclusion. We are of the opinion that the treadmill exercise will positively affect the pace of the exercise, the distance covered, the calories burnt by the children with cerebral palsy, moving more freely, controlled walking and body type.

  13. Transcription profiling reveals stage- and function-dependent expression patterns in the filarial nematode Brugia malayi

    Li Ben-Wen

    2012-05-01

    Full Text Available Abstract Background Brugia malayi is a nematode parasite that causes lymphatic filariasis, a disfiguring and disabiling tropical disease. Although a first draft genome sequence was released in 2007, very little is understood about transcription programs that govern developmental changes required for the parasite’s development and survival in its mammalian and insect hosts. Results We used a microarray with probes that represent some 85% of predicted genes to generate gene expression profiles for seven parasite life cycle stages/sexes. Approximately 41% of transcripts with detectable expression signals were differentially expressed across lifecycle stages. Twenty-six percent of transcripts were exclusively expressed in a single parasite stage, and 27% were expressed in all stages studied. K-means clustering of differentially expressed transcripts revealed five major transcription patterns that were associated with parasite lifecycle stages or gender. Examination of known stage-associated transcripts validated these data sets and suggested that newly identified stage or gender-associated transcripts may exercise biological functions in development and reproduction. The results also indicate that genes with similar transcription patterns were often involved in similar functions or cellular processes. For example, nuclear receptor family gene transcripts were upregulated in gene expression pattern four (female-enriched while protein kinase gene family transcripts were upregulated in expression pattern five (male-enriched. We also used pair-wise comparisons to identify transcriptional changes between life cycle stages and sexes. Conclusions Analysis of gene expression patterns of lifecycle in B. malayi has provided novel insights into the biology of filarial parasites. Proteins encoded by stage-associated and/or stage-specific transcripts are likely to be critically important for key parasite functions such as establishment and maintenance of

  14. Magnesium-Dependent Active-Site Conformational Selection in the Diels-Alderase Ribozyme

    Berezniak, Tomasz [University of Heidelberg; Zahran, Mai [ORNL; Imhof, Petra [University of Heidelberg; Jaeschke, Andres [Free University of Berlin; Smith, Jeremy C [ORNL

    2010-10-01

    The Diels-Alderase ribozyme, an in vitro-evolved ribonucleic acid enzyme, accelerates the formation of carbon-carbon bonds between an anthracene diene and a maleimide dienophile in a [4 + 2] cycloaddition, a reaction with broad application in organic chemistry. Here, the Diels-Alderase ribozyme is examined via molecular dynamics (MD) simulations in both crystalline and aqueous solution environments. The simulations indicate that the catalytic pocket is highly dynamic. At low Mg(2+) ion concentrations, inactive states with the catalytic pocket closed dominate. Stabilization of the enzymatically active, open state of the catalytic pocket requires a high concentration of Mg(2+) ions (e.g., 54 mM), with cations binding to specific phosphate sites on the backbone of the residues bridging the opposite strands of the pocket. The free energy profile for pocket opening at high Mg(2+) cation concentration exhibits a double minimum, with a barrier to opening of approximately 5.5 kJ/mol and the closed state approximately 3 kJ/mol lower than the open state. Selection of the open state on substrate binding leads to the catalytic activity of the ribozyme. The simulation results explain structurally the experimental observation that full catalytic activity depends on the Mg(2+) ion concentration

  15. Muscle activity pattern dependent pain development and alleviation

    Sjøgaard, Gisela; Søgaard, Karen

    2014-01-01

    Muscle activity is for decades considered to provide health benefits irrespectively of the muscle activity pattern performed and whether it is during e.g. sports, transportation, or occupational work tasks. Accordingly, the international recommendations for public health-promoting physical activity...... during physical activities at leisure and sport the motor recruitment patterns are more dynamic including regularly relatively high muscle forces - also activating type 2 muscles fibers - as well as periods of full relaxation even of the type 1 muscle fibers. Such activity is unrelated to muscle pain...

  16. Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells

    Phenobarbital (PB) induces or represses a wide spectrum of genes in rodent liver. Much less is known about its effects in human liver. We used pangenomic cDNA microarrays to analyze concentration- and time-dependent gene expression profile changes induced by PB in the well-differentiated human HepaRG cell line. Changes in gene expression profiles clustered at specific concentration ranges and treatment times. The number of correctly annotated genes significantly modulated by at least three different PB concentration ranges (spanning 0.5 to 3.2 mM) at 20 h exposure amounted to 77 and 128 genes (p ≤ 0.01) at 2- and 1.8-fold filter changes, respectively. At low concentrations (0.5 and 1 mM), PB-responsive genes included the well-recognized CAR- and PXR-dependent responsive cytochromes P450 (CYP2B6, CYP3A4), sulfotransferase 2A1 and plasma transporters (ABCB1, ABCC2), as well as a number of genes critically involved in various metabolic pathways, including lipid (CYP4A11, CYP4F3), vitamin D (CYP24A1) and bile (CYP7A1 and CYP8B1) metabolism. At concentrations of 3.2 mM or higher after 20 h, and especially 48 h, increased cytotoxic effects were associated with disregulation of numerous genes related to oxidative stress, DNA repair and apoptosis. Primary human hepatocyte cultures were also exposed to 1 and 3.2 mM PB for 20 h and the changes were comparable to those found in HepaRG cells treated under the same conditions. Taken altogether, our data provide further evidence that HepaRG cells closely resemble primary human hepatocytes and provide new information on the effects of PB in human liver. These data also emphasize the importance of investigating dose- and time-dependent effects of chemicals when using toxicogenomic approaches

  17. 3-Phosphoinositide-dependent Protein Kinase-1 (PDK1) promotes invasion and activation of matrix metalloproteinases

    Metastasis is a major cause of morbidity and mortality in breast cancer with tumor cell invasion playing a crucial role in the metastatic process. PDK1 is a key molecule that couples PI3K to cell proliferation and survival signals in response to growth factor receptor activation, and is oncogenic when expressed in mouse mammary epithelial cells. We now present evidence showing that PDK1-expressing cells exhibit enhanced anchorage-dependent and -independent cell growth and are highly invasive when grown on Matrigel. These properties correlate with induction of MMP-2 activity, increased MT1-MMP expression and a unique gene expression profile. Invasion assays in Matrigel, MMP-2 zymogram analysis, gene microarray analysis and mammary isografts were used to characterize the invasive and proliferative function of cells expressing PDK1. Tissue microarray analysis of human breast cancers was used to measure PDK1 expression in invasive tumors by IHC. Enhanced invasion on Matrigel in PDK1-expressing cells was accompanied by increased MMP-2 activity resulting from stabilization against proteasomal degradation. Increased MMP-2 activity was accompanied by elevated levels of MT1-MMP, which is involved in generating active MMP-2. Gene microarray analysis identified increased expression of the ECM-associated genes decorin and type I procollagen, whose gene products are substrates of MT1-MMP. Mammary fat pad isografts of PDK1-expressing cells produced invasive adenocarcinomas. Tissue microarray analysis of human invasive breast cancer indicated that PDK1pSer241 was strongly expressed in 90% of samples. These results indicate that PDK1 serves as an important effector of mammary epithelial cell growth and invasion in the transformed phenotype. PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collagen. The presence of increased PDK1 expression in the majority of invasive breast cancers suggests its

  18. Microbial expression profiles in the rhizosphere of willows depend on soil contamination

    Yergeau, Etienne; Sanschagrin, Sylvie; Maynard, Christine; St-Arnaud, Marc; Greer, Charles W.

    2013-01-01

    The goal of phytoremediation is to use plants to immobilize, extract or degrade organic and inorganic pollutants. In the case of organic contaminants, plants essentially act indirectly through the stimulation of rhizosphere microorganisms. A detailed understanding of the effect plants have on the activities of rhizosphere microorganisms could help optimize phytoremediation systems and enhance their use. In this study, willows were planted in contaminated and non-contaminated soils in a greenh...

  19. Plant root transcriptome profiling reveals a strain-dependent response during Azospirillum-rice cooperation

    Benoît eDrogue

    2014-11-01

    Full Text Available Cooperation involving Plant Growth-Promoting Rhizobacteria results in improvements of plant growth and health. While pathogenic and symbiotic interactions are known to induce transcriptional changes for genes related to plant defence and development, little is known about the impact of phytostimulating rhizobacteria on plant gene expression. This study aims at identifying genes significantly regulated in rice roots upon Azospirillum inoculation, considering possible favored interaction between a strain and its original host cultivar. Genome-wide analyses of Oryza sativa japonica cultivars Cigalon and Nipponbare were performed, by using microarrays, seven days post inoculation with A. lipoferum 4B (isolated from Cigalon or Azospirillum sp. B510 (isolated from Nipponbare and compared to the respective non-inoculated condition. A total of 7,384 genes were significantly regulated, which represent about 16 % of total rice genes. A set of 34 genes is regulated by both Azospirillum strains in both cultivars, including a gene orthologous to PR10 of Brachypodium, and these could represent plant markers of Azospirillum-rice interactions. The results highlight a strain-dependent response of rice, with 83 % of the differentially expressed genes being classified as combination-specific. Whatever the combination, most of the differentially expressed genes are involved in primary metabolism, transport, regulation of transcription and protein fate. When considering genes involved in response to stress and plant defence, it appears that strain B510, a strain displaying endophytic properties, leads to the repression of a wider set of genes than strain 4B. Individual genotypic variations could be the most important driving force of rice roots gene expression upon Azospirillum inoculation. Strain-dependent transcriptional changes observed for genes related to auxin and ethylene signalling highlight the complexity of hormone signalling networks in the Azospirillum

  20. Network-dependent modulation of brain activity during sleep

    Watanabe, T.; Kan, S.; Koike, T.; Misaki, M; Konishi, S.; Miyauchi, S; Miyahsita, Y.; Masuda, N.

    2014-01-01

    Brain activity dynamically changes even during sleep. A line of neuroimaging studies has reported changes in functional connectivity and regional activity across different sleep stages such as slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. However, it remains unclear whether and how the large-scale network activity of human brains changes within a given sleep stage. Here, we investigated modulation of network activity within sleep stages by applying the pairwise maximum entropy mod...

  1. Separation of DNA-dependent polymerate activities in Micrococcus radiodurans

    DNA polymerase activities in Micrococcus radiodurans were separated into two fractions after purification more than 2000 fold. They differ in pH optimum and residual activities in the absence of a full deoxyribonucleoside triphosphates complement. NAD partly inhibited one of the activities. Both activities were eluted as a single peak on gel filtration and sedimented at the same rate on glycerol gradient centrifugation. Molecular weight 140000 was calculated from Stokes radius and sedimentation constant. Deoxyribonuclease activity was detected on one of the polymerase activities which preferentially degraded double-stranded DNA. Priming activity of nicked DNA was reduced by γ-radiation. These results have been related to the possible roles in repair synthesis in vivo or DNA synthesis in permeable cells of M. radiodurans

  2. PPARδ activation acts cooperatively with 3-phosphoinositide-dependent protein kinase-1 to enhance mammary tumorigenesis.

    Claire B Pollock

    Full Text Available Peroxisome proliferator-activated receptorδ (PPARδ is a transcription factor that is associated with metabolic gene regulation and inflammation. It has been implicated in tumor promotion and in the regulation of 3-phosphoinositide-dependent kinase-1 (PDK1. PDK1 is a key regulator of the AGC protein kinase family, which includes the proto-oncogene AKT/PKB implicated in several malignancies, including breast cancer. To assess the role of PDK1 in mammary tumorigenesis and its interaction with PPARδ, transgenic mice were generated in which PDK1 was expressed in mammary epithelium under the control of the MMTV enhancer/promoter region. Transgene expression increased pT308AKT and pS9GSK3β, but did not alter phosphorylation of mTOR, 4EBP1, ribosomal protein S6 and PKCα. The transgenic mammary gland also expressed higher levels of PPARδ and a gene expression profile resembling wild-type mice maintained on a diet containing the PPARδ agonist, GW501516. Both wild-type and transgenic mice treated with GW501516 exhibited accelerated rates of tumor formation that were more pronounced in transgenic animals. GW501516 treatment was accompanied by a distinct metabolic gene expression and metabolomic signature that was not present in untreated animals. GW501516-treated transgenic mice expressed higher levels of fatty acid and phospholipid metabolites than treated wild-type mice, suggesting the involvement of PDK1 in enhancing PPARδ-driven energy metabolism. These results reveal that PPARδ activation elicits a distinct metabolic and metabolomic profile in tumors that is in part related to PDK1 and AKT signaling.

  3. GENOMIC PROFILING BY MULTIPLEX LIGATION - DEPENDENT PROBE AMPLIFICATION IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS

    Georgiana-Emilia Grigore

    2013-11-01

    Full Text Available The clinical management of severe pathological conditions, such as B-cell chronic lymphocytic leukemia (B-CLL, is subject to continuous optimization and re-evaluation. Patients may fully benefit from rapid, standardized laboratory tools designed to facilitate their early stratification according to disease risk, stage and prognosis. Such technologies may also aid the clinician in selecting the therapeutic option with the greatest chances of success. The presence of specific genetic abnormalities are frequently associated with the clinical outcome of oncologic patients in general, and B-CLL patients in particular. In the current study, a group of 58 B-CLL patients were evaluated for the detection of gene copy number alterations (deletions or duplication/ amplifications within 45 distinct genetic targets, by means of a novel molecular methodology, Multiplex Ligation - Dependent Probe Amplification (MLPA. Simple or complex genetic defects were identified in 67% of cases, and the most common aberrations observed were: deletion of the short arm of chromosome 13 in 33% of cases, deletion of the long arm of chromosome 11 in 16% of cases, trisomy 12 in 16% of cases, and deletion of the short arm of chromosome 17 in 7% of cases. The main conclusion of the study presented here points towards MLPA as a potential key step of clinical management protocols in B-CLL, providing that it will be fully standardised for routine diagnosis.

  4. Temperature-dependent dielectric properties and line profile analysis of zinc-substituted copper ferrites

    Lamani, A. R.; Jayanna, H. S.; Naveen, C. S.; Rajeeva, M. P.; Prasanna, G. D.; Chaturmukha, V. S.; Harish, B. M.; Suresh, S.; Avinash, B. S.

    2016-05-01

    Temperature dependence of dielectric constant and loss has been investigated for different compositions of Zinc substituted copper ferrites with general formula Cu1-xZnxFe2O4 (x = 0.0, 0.2, 0.4, 0.6, 0.8, 1.0) prepared by ceramic method. XRD analysis confirms all the samples exhibit single phase cubic spinel structure. The dielectric constant and loss of the sample were studied in the temperature ranges from RT to 1000K at different constant frequency. Samples of the composition with x = 0.8 show low dielectric loss up to a measured temperature around 770 °C at higher frequencies as compared to samples of other compositions. A plot of dielectric constant versus temperature shows a transition near the Curie temperature, an attempt is made to explain the possible mechanism for this observation. The dielectric constant increases slowly from 309°C to 770°C with temperature in the beginning and sharply decreases with increase in frequency for all the samples. The variation of tanδ with frequency shows cusps for all the samples except for x = 0.6. These variations have been explained on the basis of Koop's phenomenological theory. The variation of dielectric loss tangent with frequency showed maxima for the 1 KHz. These maxima are also found to shift towards low-frequency region as the content of Zn increases.

  5. Activity Profiles and Physiological Responses of Representative Tag Football Players in Relation to Playing Position and Physical Fitness

    Luke W Hogarth; Burkett, Brendan J; McKean, Mark R.

    2015-01-01

    This study determined the physical fitness, match-activity profiles and physiological responses of representative tag football players and examined the relationship between physical fitness and the match-activity profile. Microtechnology devices and heart rate (HR) chest straps were used to determine the match-activity profiles of sixteen tag football players for five matches during the 2014 Australian National Championships. The relationships between lower body muscular power, straight line ...

  6. Temporal dependence of cysteine protease activation following excitotoxic hippocampal injury

    Berry, Jennifer N.; Sharrett-Field, Lynda; Butler, Tracy R.; Prendergast, Mark A.

    2012-01-01

    Excitotoxic insults can lead to intracellular signaling cascades that contribute to cell death, in part by activation of proteases, phospholipases, and endonucleases. Cysteine proteases, such as calpains, are calcium-activated enzymes which degrade cytoskeletal proteins, including microtubule-associated proteins, tubulin, and spectrin, among others. The current study used the organotypic hippocampal slice culture model to examine whether pharmacologic inhibition of cysteine protease activity ...

  7. GENETIC ACTIVITY PROFILES AND PATTERN RECOGNITION IN TEST BATTERY SELECTION (JOURNAL VERSION)

    Computer-generated genetic activity profiles and pairwise matching procedures may aid in the selection of the most appropriate short-term bioassays to be used in test batteries for the evaluation of the genotoxicity of a given chemical or group of chemicals. Selection of test bat...

  8. Assimilation of active microwave observation data for soil moisture profile estimation

    Hoeben, R.; Troch, P.A.

    2000-01-01

    This paper discusses the potential of retrieving information about the soil moisture profile from measurements of the surface soil moisture content through active microwave observations of the Earth. Recently, Mancini et al. [1999] have shown through laboratory experiments that the volumetric moistu

  9. A comparison of the activity profile and physiological demands between advanced and recreational veteran tennis players

    J. Fernandez-Fernandez; D. Sanz-Rivas; C. Sanchez-Muñoz; B.M. Pluim; I. Tiemessen; A. Mendez-Villanueva

    2009-01-01

    The aim of the study was to examine whether differences in playing level influence the activity profile and physiological demands of advanced and recreational veteran men's tennis players during an hour of tennis match play. Ten advanced (International Tennis Number [ITN] 3-5, 45.3 +/- 5.1 years) an

  10. Elemental profiles of soil in and around Tirupati by reactor neutron activation using KO method

    Soil samples, representatives of various places in and around Tirupati, Andhra Pradesh, that are affected by industrial effluents and sewages, were analysed for the elemental profiles by neutron activation analysis (NAA) using Ko method. Concentrations of 23 elements were measured. Variation in concentration of important elements with respect to influence on vegetation is discussed. (author). 2 refs., 1 tab

  11. Hα Surface Brightness Profiles of Star-Forming Galaxies and Dependence on Halo Mass Using the HAGGIS Survey

    Kulkarni, S.; Wilman, D.; Erwin, P.; Koppenhöfer, J.; Gutierrez, L.; Beckman, J.; Saglia, R.; Bender, R.

    2014-03-01

    We present the first results from the Hα Galaxy Groups Imaging Survey (HAGGIS), a narrow-band imaging survey of SDSS groups at z Issac Newton Telescope (INT). In total, we observed 100 galaxy groups with a wide range of halo mass (1012 - 1014 M⊙) in pairs of narrow-band filters selected to get continuum subtracted rest-frame Hα images for each galaxy. The excellent data allows us to detect Hα down to the 10-18 ergs/s/cm2/arcsec2 level. Here, we examine the role played by halo mass and galaxy stellar mass in deciding the overall star formation activity in star forming disks by comparing stacked Hα profiles of galaxies in different halo mass and stellar mass bins. With this preliminary study, we have found that the star-formation activity in star-forming galaxies decreases in larger halos compared to the field galaxies. Using median equivalent width profiles, we can infer how environmental processes affect star-forming galaxies differently at different radii.

  12. Transient thermal analysis of longitudinal fins with internal heat generation considering temperature-dependent properties and different fin profiles

    Highlights: • Transient thermal analysis of the longitudinal fins is presented. • The properties of fin are considered as a function of temperature. • An approximate technique named Hybrid DTM–FDM is used for solving the problem. • The effect of physical parameters on temperature distribution is investigated. - Abstract: The present paper aims to study the transient thermal analysis of longitudinal fins with variable cross section considering internal heat generation. The profile shapes of the fins are considered rectangular, convex, triangular and concave. It is assumed that both thermal conductivity and internal heat generation are as linear functions of temperature. The power-law temperature-dependent model is used to simulate different types of heat transfer such as laminar film boiling, natural convection, nucleate boiling and radiation. The governing equation is derived as a nonlinear partial differential equation (PDE) that is solved using a hybrid approximate technique based on the differential transform method (DTM) and finite difference method (FDM). The results are presented to study the effects of some physical parameters such as fin profile shape, thermal conductivity, convection heat transfer coefficient and internal heat generation

  13. Seismic constraints on the radial dependence of the internal rotation profiles of six Kepler subgiants and young red giants

    Deheuvels, S; Goupil, M J; Appourchaux, T; Benomar, O; Bruntt, H; Campante, T L; Casagrande, L; Ceillier, T; Davies, G R; De Cat, P; Fu, J N; García, R A; Lobel, A; Mosser, B; Reese, D R; Regulo, C; Schou, J; Stahn, T; Thygesen, A O; Yang, X H; Chaplin, W J; Christensen-Dalsgaard, J; Eggenberger, P; Gizon, L; Mathis, S; Molenda-Żakowicz, J; Pinsonneault, M

    2014-01-01

    Context : We still do not know which mechanisms are responsible for the transport of angular momentum inside stars. The recent detection of mixed modes that contain the signature of rotation in the spectra of Kepler subgiants and red giants gives us the opportunity to make progress on this issue. Aims: Our aim is to probe the radial dependance of the rotation profiles for a sample of Kepler targets. For this purpose, subgiants and early red giants are particularly interesting targets because their rotational splittings are more sensitive to the rotation outside the deeper core than is the case for their more evolved counterparts. Methods: We first extract the rotational splittings and frequencies of the modes for six young Kepler red giants. We then perform a seismic modeling of these stars using the evolutionary codes CESAM2k and ASTEC. By using the observed splittings and the rotational kernels of the optimal models, we perform inversions of the internal rotation profiles of the six stars. Results: We obtai...

  14. Application of time-dependent Raman theory to Raman excitation profiles of hexamethylbenzene-tetracyanoethylene electron donor-acceptor complex

    Britt, B.M.; McHale, J.L. [Univ. of Idaho, Moscow, ID (United States); Friedrich, D.M. [Pacific Northwest Lab., Richland, WA (United States)

    1995-04-27

    Raman excitation and absorption profiles were obtained for the 1:1 electron donor-acceptor complex of hexamethylbenzene with tetracyanoethylene in dichloromethane solution. The absorption and Raman profiles were analyzed using the time-dependent theory of Heller to obtain the displacements and non-Condon factors for the four strongest Raman modes, the electronic excitation energy, the transition dipole, and solvent line-broadening parameters. The results are compared to the data reported by Myers et al. for the same complex in carbon tetrachloride solution. Attempts to account for solvent effects on the normal-mode displacements in terms of the solvent local field lead are complicated by the effect of the solvent on the structure of the complex. We propose that in CH{sub 2}Cl{sub 2} but not in CCl{sub 4}, the complex adopts a low-symmetry ground-state geometry which permits vibronic coupling of the charge-transfer and locally excited (TCNE) states. 33 refs., 7 figs., 4 tabs.

  15. Activity based protein profiling to detect serine hydrolase alterations in virus infected cells

    MdShahiduzzaman; KevinM.Coombs

    2012-01-01

    Activity-based protein profiling (ABPP) is a newly emerging technique that uses active site-directed probes to monitor the functional status of enzymes. Serine hydrolases are one of the largest families of enzymes in mammals. More than 200 serine hydrolases have been identified, but little is known about their specific roles. Serine hydrolases are involved in a variety of physiological functions, including digestion, immune response, blood coagulation, and reproduction. ABPP has been used rec...

  16. Lipid Profile and Serum Paraoxonase1 Activity in CRF Patients Pre and Posthemodialysis

    Nitin S. Nagane1* and Jayshree V. Ganu2

    2011-01-01

    Chronic renal failure (CRF) is associated with an increased risk of cardiovascular disease (CVD). In the present study, 30 CRF patients undergoing hemodialysis and 50 healthy controls matching in age and sex were included. We have estimated blood urea, serum creatinine, lipid profile and serum Paraoxonase1 (PON1) activity in pre and post hemodialytic samples. HDL-Cholesterol (HDLC) and serum Paraoxonase1(PON1) activity was found to be significantly reduced (P

  17. Clinico-demographic profile, sexual dysfunction and readiness to change in male alcohol dependence syndrome inpatients in a tertiary hospital.

    Pandey, A K; Sapkota, N; Tambi, A; Shyangwa, P M

    2012-03-01

    Persons with prolonged and heavy alcohol use generally suffer from alcohol dependence syndrome (ADS) and develop physical, sexual as well as psychiatric co-morbidity. Successful recovery to normalcy depends on multiple factors including patient's motivation. To study clinico-demographic profile, reasons for initiating alcohol use, sexual and psychiatric disorders and eagerness for treatment and quitting alcohol in ADS inpatients. Fifty consecutive ADS inpatients with matching controls were enrolled. Clinico-demographic profile, factors for initiating alcohol use, psychiatric and sexual co-morbidity and want for treatment and being abstinent was studied applying relevant scales. All subjects were males with a mean age of 37.5 years, 80% were married, majority were Hindu (88%) and from nuclear families (56%). Fifty two percent had an education level of Graduation or more and 68% of patients reported peer pressure to be the initiating factor for alcohol use. Seventy six percent had psychiatric co-morbidity including personality Problems and other Psychiatric disorders 19(38%), delirium tremens 14 (28.00%) and Mood disorders 12(24%).Depression being most common mood disorder (14%). Nicotine was the most common other substance of use 32 (64%). Sixty eight percent of the patient reported one or another sexual dysfunction. 68% of ADS inpatients acknowledged of having problems related to their drinking, expressed desire for change and were eager to avail treatment and to remain abstinent. ADS patients commonly suffer from psychiatric co-morbidity and sexual dysfunctions. They also wish to have effective treatment and to quit alcohol. PMID:23441492

  18. Efficacy of treatment in an opioid –dependent population group using the Maudsley Addiction Profile (MAP) tool

    Collins, Ruth; Boggs, Bob; Taggart, Noel; Kelly, Martin; Drillington, Aileen; Swanton, Ivy; Patterson, Diane

    2009-01-01

    A pilot study was performed to assess the effectiveness of treatment in an opioid dependent population using the Maudsley Addiction Profile (MAP) tool1. The primary outcome of the study was to assess if treatment had an effect on 1. Substance use (quantity and frequency of use), 2. Health risk behaviour (injecting and sharing injecting equipment), 3. Health symptoms (physical and psychological) and 4. Personal /Social functioning (relationships, employment and crime). A secondary outcome was also sought. The study took place in 2007 in an inner city Belfast hospital specialising in the treatment of addiction, over a two month period. Fifteen patients, all opioid dependent and receiving outpatient community treatment, were interviewed at baseline (prior to the commencement of treatment) and at eight weeks follow up. Three patients were lost to follow up. Two patients stopped using altogether. Of the remaining patients, improvements were seen in most areas. There was a decrease in the use of heroin (71.28%), cocaine (99.72%), crack cocaine (100%), cannabis (99.94%) and alcohol (33.17%). There was a reduction in injecting behaviour (60.93%). Improvements were observed in health with a reduction in physical (41.35%) and psychological (35%) symptoms. Overall personal and social functioning improved regarding interactions with family and friends. A reduction in crime was also observed (75%). Opinions and views of staff involved in the study were generally positive. This patient population presents with multiple and complex needs. Effective treatment needs to address these needs and not just drug addiction alone. The Maudsley Addiction Profile tool highlights this. PMID:19252726

  19. Task-dependent modulation of oscillatory neural activity during movements

    Herz, D. M.; Christensen, M. S.; Reck, C.;

    2011-01-01

    -dependent modulation of frequency coupling within this network. To this end we recorded 122-multichannel EEG in 13 healthy subjects while they performed three simple motor tasks. EEG data source modeling using individual MR images was carried out with a multiple source beamformer approach. A bilateral motor network...

  20. Sequential Reinstatement of Neocortical Activity during Slow Oscillations Depends on Cells’ Global Activity

    Peyrache, Adrien; Benchenane, Karim; Khamassi, Mehdi; Wiener, Sidney I.; Battaglia, Francesco P.

    2009-01-01

    During Slow Wave Sleep (SWS), cortical activity is dominated by endogenous processes modulated by slow oscillations (0.1–1 Hz): cell ensembles fluctuate between states of sustained activity (UP states) and silent epochs (DOWN states). We investigate here the temporal structure of ensemble activity during UP states by means of multiple single unit recordings in the prefrontal cortex of naturally sleeping rats. As previously shown, the firing rate of each PFC cell peaks at a distinct time lag after the DOWN/UP transition in a consistent order. We show here that, conversely, the latency of the first spike after the UP state onset depends primarily on the session-averaged firing rates of cells (which can be considered as an indirect measure of their intrinsic excitability). This latency can be explained by a simple homogeneous process (Poisson model) of cell firing, with sleep averaged firing rates employed as parameters. Thus, at DOWN/UP transitions, neurons are affected both by a slow process, possibly originating in the cortical network, modulating the time course of firing for each cell, and by a fast, relatively stereotyped reinstatement of activity, related mostly to global activity levels. PMID:20130754

  1. 75 FR 62636 - Proposed Information Collection (Status of Dependents Questionnaire) Activity: Comment Request

    2010-10-12

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Proposed Information Collection (Status of Dependents Questionnaire) Activity: Comment Request... techniques or the use of other forms of information technology. Title: Status of Dependents Questionnaire,...

  2. 78 FR 46422 - Proposed Information Collection (Status of Dependents Questionnaire) Activity: Comment Request

    2013-07-31

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Proposed Information Collection (Status of Dependents Questionnaire) Activity: Comment Request... of Dependents Questionnaire, VA Form 21-0538. OMB Control Number: 2900-0500. Type of...

  3. Expression profiling of serum inducible genes identifies a subset of SRF target genes that are MKL dependent

    Prywes Ron

    2004-08-01

    Full Text Available Abstract Background Serum Response Factor (SRF is a transcription factor that is required for the expression of many genes including immediate early genes, cytoskeletal genes, and muscle-specific genes. SRF is activated in response to extra-cellular signals by its association with a diverse set of co-activators in different cell types. In the case of the ubiquitously expressed immediate early genes, the two sets of SRF binding proteins that regulate its activity are the TCF family of proteins that include Elk1, SAP1 and SAP2 and the myocardin-related MKL family of proteins that include MKL1 and MKL2 (also known as MAL, MRTF-A and -B and BSAC. In response to serum or growth factors these two classes of co-activators are activated by different upstream signal transduction pathways. However, it is not clear how they differentially activate SRF target genes. Results In order to identify the serum-inducible SRF target genes that are specifically dependent on the MKL pathway, we have performed microarray experiments using a cell line that expresses dominant negative MKL1. This approach was used to identify SRF target genes whose activation is MKL-dependent. Twenty-eight of 150 serum-inducible genes were found to be MKL-dependent. The promoters of the serum-inducible genes were analyzed for SRF binding sites and other common regulatory elements. Putative SRF binding sites were found at a higher rate than in a mouse promoter database but were only identified in 12% of the serum-inducible promoters analyzed. Additional partial matches to the consensus SRF binding site were found at a higher than expected rate in the MKL-dependent gene promoters. The analysis for other common regulatory elements is discussed. Conclusions These results suggest that a subset of immediate early and SRF target genes are activated by the Rho-MKL pathway. MKL may also contribute to the induction of other SRF target genes however its role is not essential, possibly due to other

  4. Effects of gamma irradiation on chickpea seeds vis-a-vis total seed storage proteins, antioxidant activity and protein profiling.

    Bhagyawant, S S; Gupta, N; Shrivastava, N

    2015-01-01

    The present work describes radiation—induced effects on seed composition vis—à—vis total seed proteins, antioxidant levels and protein profiling employing two dimensional gel electrophoresis (2D—GE) in kabuli and desi chickpea varities. Seeds were exposed to the radiation doses of 1,2,3,4 and 5 kGy. The total protein concentrations decreased and antioxidant levels were increased with increasing dose compared to control seed samples. Radiation induced effects were dose dependent to these seed parameters while it showed tolerance to 1 kGy dose. Increase in the dose was complimented with increase in antioxidant levels, like 5 kGy enhanced % scavenging activities in all the seed extracts. Precisely, the investigations reflected that the dose range from 2 to 5 kGy was effective for total seed storage proteins, as depicted quantitatively and qualitative 2D—GE means enhance antioxidant activities in vitro. PMID:26516115

  5. Activity-dependent acceleration of endocytosis at a central synapse.

    Wu, Wei; Xu, Jianhua; Wu, Xin-Sheng; Wu, Ling-Gang

    2005-12-14

    Accumulated evidence indicates the existence of rapid and slow endocytosis at many synapses. It has been proposed that rapid endocytosis is activated by intense stimulation when vesicle recycling needs to be speeded up to supply vesicles at hippocampal synapses. However, the evidence, as obtained with imaging techniques, which are somewhat indirect in indicating rapid endocytosis, is controversial. Furthermore, a slower time course of endocytosis is often found after more intense nerve activity, casting doubt on the role of rapid endocytosis at synapses. Here, we addressed this issue at a mammalian central synapse, the calyx of Held, using a capacitance measurement technique that provides a higher time resolution than imaging techniques. We found that rapid endocytosis with a time constant of approximately 1-2 s was activated during intense nerve activity. Reducing the presynaptic calcium current or buffering the intracellular calcium with EGTA significantly inhibited rapid endocytosis, suggesting that calcium triggers rapid endocytosis. During intense stimulation, rapid endocytosis retrieved up to approximately eight vesicles per second per active zone, approximately eightfold larger than reported in the hippocampus, and thus played a dominant role during and within 3 s after intense stimulation. Slow endocytosis became dominant 3 s after intense stimulation likely because of the fall of the intracellular calcium level that deactivated rapid endocytosis. These results underscore the importance of calcium-triggered rapid endocytosis, which offers the nerve terminal the plasticity to speed up vesicle cycling during intense nerve activity. PMID:16354926

  6. Profiling of Concanavalin A-Binding Glycoproteins in Human Hepatic Stellate Cells Activated with Transforming Growth Factor-β1

    Yannan Qin

    2014-11-01

    Full Text Available Glycoproteins play important roles in maintaining normal cell functions depending on their glycosylations. Our previous study indicated that the abundance of glycoproteins recognized by concanavalin A (ConA was increased in human hepatic stellate cells (HSCs following activation by transforming growth factor-β1 (TGF-β1; however, little is known about the ConA-binding glycoproteins (CBGs of HSCs. In this study, we employed a targeted glycoproteomics approach using lectin-magnetic particle conjugate-based liquid chromatography-tandem mass spectrometry to compare CBG profiles between LX-2 HSCs with and without activation by TGF-β1, with the aim of discovering novel CBGs and determining their possible roles in activated HSCs. A total of 54 and 77 proteins were identified in the quiescent and activated LX-2 cells, respectively. Of the proteins identified, 14.3% were glycoproteins and 73.3% were novel potential glycoproteins. Molecules involved in protein processing in the endoplasmic reticulum (e.g., calreticulin and calcium signaling (e.g., 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase β-2 [PLCB2] were specifically identified in activated LX-2 cells. Additionally, PLCB2 expression was upregulated in the cytoplasm of the activated LX-2 cells, as well as in the hepatocytes and sinusoidal cells of liver cirrhosis tissues. In conclusion, the results of this study may aid future investigations to find new molecular mechanisms involved in HSC activation and antifibrotic therapeutic targets.

  7. Investigating the active hydrothermal field of Kolumbo Volcano using CTD profiling

    Eleni Christopoulou, Maria; Mertzimekis, Theo; Nomikou, Paraskevi; Papanikolaou, Dimitrios; Carey, Steve

    2014-05-01

    The submarine Kolumbo volcano NE of Santorini Island and the unique active hydrothermal vent field on its crater field (depth ~ 500 m) have been recently explored in multiple cruises aboard E/V Nautilus. ROV explorations showed the existence of extensive vent activity and almost completely absence of vent-specific macrofauna. Gas discharges have been found to be 99%-rich in CO2, which is sequestered at the bottom of the crater due to a special combination of physicochemical and geomorphological factors. The dynamic conditions existing along the water column in the crater have been studied in detail by means of temperature, salinity and conductivity depth profiles for the first time. CTD sensors aboard the ROV Hercules were employed to record anomalies in those parameters in an attempt to investigate several active and inactive vent locations. Temporal CTD monitoring inside and outside of the crater was carried out over a period of two years. Direct comparison between the vent field and locations outside the main cone, where no hydrothermal activity is known to exist, showed completely different characteristics. CTD profiles above the active vent field (NNE side) are correlated to Kolumbo's cone morphology. The profiles suggest the existence of four distinct zones of physicochemical properties in the water column. The layer directly above the chimneys exhibit gas discharges highly enriched in CO2. Continuous gas motoring is essential to identify the onset of geological hazards in the region.

  8. Time-dependent expression profiles of microRNAs and mRNAs in rat milk whey.

    Hirohisa Izumi

    Full Text Available Functional RNAs, such as microRNA (miRNA and mRNA, are present in milk, but their roles are unknown. To clarify the roles of milk RNAs, further studies using experimental animals such as rats are needed. However, it is unclear whether rat milk also contains functional RNAs and what their time dependent expression profiles are. Thus, we prepared total RNA from whey isolated from rat milk collected on days 2, 9, and 16 postpartum and analyzed using microarrays and quantitative PCR. The concentration of RNA in colostrum whey (day 2 was markedly higher than that in mature milk whey (days 9 and 16. Microarray analysis detected 161 miRNAs and 10,948 mRNA transcripts. Most of the miRNAs and mRNA transcripts were common to all tested milks. Finally, we selected some immune- and development-related miRNAs and mRNAs, and analysed them by quantitative PCR (in equal sample volumes to determine their time-dependent changes in expression in detail. Some were significantly more highly expressed in colostrum whey than in mature milk whey, but some were expressed equally. And mRNA expression levels of some cytokines and hormones did not reflect the protein levels. It is still unknown whether RNAs in milk play biological roles in neonates. However, our data will help guide future in vivo studies using experimental animals such as rats.

  9. Heating and active control of profiles and transport by IBW in the HT-7 tokamak

    Significant progress on Ion Bernstein Wave (IBW) heating and control of profiles has been obtained in HT-7. Both on-axis and off-axis electron heating with global peaked and local steep electron pressure profiles were realized if the position of the resonant layer was selected to be plasma far from the plasma edge region. Reduction of electron heat transport has been observed from sawtooth heat pulse propagation. Improvement of both particle and energy confinement was slight in the on-axis and considerable in the off-axis heating cases. The improved confinement in off-axis heating mode may be due to the extension of the high performance plasma volume caused by IBW. These studies demonstrate that IBWs are potentially a tool for active control of plasma profiles and transport. (author)

  10. Autoregressive higher-order hidden Markov models: exploiting local chromosomal dependencies in the analysis of tumor expression profiles.

    Michael Seifert

    Full Text Available Changes in gene expression programs play a central role in cancer. Chromosomal aberrations such as deletions, duplications and translocations of DNA segments can lead to highly significant positive correlations of gene expression levels of neighboring genes. This should be utilized to improve the analysis of tumor expression profiles. Here, we develop a novel model class of autoregressive higher-order Hidden Markov Models (HMMs that carefully exploit local data-dependent chromosomal dependencies to improve the identification of differentially expressed genes in tumor. Autoregressive higher-order HMMs overcome generally existing limitations of standard first-order HMMs in the modeling of dependencies between genes in close chromosomal proximity by the simultaneous usage of higher-order state-transitions and autoregressive emissions as novel model features. We apply autoregressive higher-order HMMs to the analysis of breast cancer and glioma gene expression data and perform in-depth model evaluation studies. We find that autoregressive higher-order HMMs clearly improve the identification of overexpressed genes with underlying gene copy number duplications in breast cancer in comparison to mixture models, standard first- and higher-order HMMs, and other related methods. The performance benefit is attributed to the simultaneous usage of higher-order state-transitions in combination with autoregressive emissions. This benefit could not be reached by using each of these two features independently. We also find that autoregressive higher-order HMMs are better able to identify differentially expressed genes in tumors independent of the underlying gene copy number status in comparison to the majority of related methods. This is further supported by the identification of well-known and of previously unreported hotspots of differential expression in glioblastomas demonstrating the efficacy of autoregressive higher-order HMMs for the analysis of individual

  11. The cell biology of T-dependent B cell activation

    Owens, T; Zeine, R

    1989-01-01

    The requirement that CD4+ helper T cells recognize antigen in association with class II Major Histocompatibility Complex (MHC) encoded molecules constrains T cells to activation through intercellular interaction. The cell biology of the interactions between CD4+ T cells and antigen-presenting cells...

  12. Incorporating Nondrug Social & Recreational Activities in Outpatient Chemical Dependency Treatment

    Siporin, Sheldon; Baron, Lisa

    2012-01-01

    "Contingency Management programs (CMP) and non-drug social and recreational activities (NDSRA) are interventions premised on behavior theory that rely on external sources of reinforcement alternative to drug-based forms to decrease drug use. CMP usually employs vouchers as reinforcement for negative toxicologies. Despite research support, CMP…

  13. Locality and Word Order in Active Dependency Formation in Bangla.

    Chacón, Dustin A; Imtiaz, Mashrur; Dasgupta, Shirsho; Murshed, Sikder M; Dan, Mina; Phillips, Colin

    2016-01-01

    Research on filler-gap dependencies has revealed that there are constraints on possible gap sites, and that real-time sentence processing is sensitive to these constraints. This work has shown that comprehenders have preferences for potential gap sites, and immediately detect when these preferences are not met. However, neither the mechanisms that select preferred gap sites nor the mechanisms used to detect whether these preferences are met are well-understood. In this paper, we report on three experiments in Bangla, a language in which gaps may occur in either a pre-verbal embedded clause or a post-verbal embedded clause. This word order variation allows us to manipulate whether the first gap linearly available is contained in the same clause as the filler, which allows us to dissociate structural locality from linear locality. In Experiment 1, an untimed ambiguity resolution task, we found a global bias to resolve a filler-gap dependency with the first gap linearly available, regardless of structural hierarchy. In Experiments 2 and 3, which use the filled-gap paradigm, we found sensitivity to disruption only when the blocked gap site is both structurally and linearly local, i.e., the filler and the gap site are contained in the same clause. This suggests that comprehenders may not show sensitivity to the disruption of all preferred gap resolutions. PMID:27610090

  14. Phytochemical profiles, antioxidant activities of functional herb Abrus cantoniensis and Abrus mollis.

    Yang, Mei; Shen, Qing; Li, Lin-Qiu; Huang, Ye-Qing; Cheung, Hon-Yeung

    2015-06-15

    It has been claimed that consumptions of Abrus cantoniensis (AC) and Abrus mollis (AM) as folk beverages and soups are good to cleanse liver toxicants and prevent liver diseases. There is scant information on the phytochemical profiles and antioxidant activities of these two varieties. Five major phytochemicals in these two cultivars were qualitatively and quantitatively compared using UPLC-PDA. A high level of total phenolic content (TPC) and total flavonoid content (TFC) was found in AC and AM. AC, in general, showed some antioxidant activities comparable to that of BHT, and stronger radical scavenging activities and higher reducing power than that of AM (pfoods or beverages to promote health function. PMID:25660890

  15. Comparative Analysis of Click Chemistry Mediated Activity-Based Protein Profiling in Cell Lysates

    Yinliang Yang

    2013-10-01

    Full Text Available Activity-based protein profiling uses chemical probes that covalently attach to active enzyme targets. Probes with conventional tags have disadvantages, such as limited cell permeability or steric hindrance around the reactive group. A tandem labeling strategy with click chemistry is now widely used to study enzyme targets in situ and in vivo. Herein, the probes are reacted in live cells, whereas the ensuing detection by click chemistry takes place in cell lysates. We here make a comparison of the efficiency of the activity-based tandem labeling strategy by using Cu(I-catalyzed and strain-promoted click chemistry, different ligands and different lysis conditions.

  16. Mercury (Hg) in meteorites: Variations in abundance, thermal release profile, mass-dependent and mass-independent isotopic fractionation

    Meier, Matthias M. M.; Cloquet, Christophe; Marty, Bernard

    2016-06-01

    We have measured the concentration, isotopic composition and thermal release profiles of Mercury (Hg) in a suite of meteorites, including both chondrites and achondrites. We find large variations in Hg concentration between different meteorites (ca. 10 ppb to 14,000 ppb), with the highest concentration orders of magnitude above the expected bulk solar system silicates value. From the presence of several different Hg carrier phases in thermal release profiles (150-650 °C), we argue that these variations are unlikely to be mainly due to terrestrial contamination. The Hg abundance of meteorites shows no correlation with petrographic type, or mass-dependent fractionation of Hg isotopes. Most carbonaceous chondrites show mass-independent enrichments in the odd-numbered isotopes 199Hg and 201Hg. We show that the enrichments are not nucleosynthetic, as we do not find corresponding nucleosynthetic deficits of 196Hg. Instead, they can partially be explained by Hg evaporation and redeposition during heating of asteroids from primordial radionuclides and late-stage impact heating. Non-carbonaceous chondrites, most achondrites and the Earth do not show these enrichments in vapor-phase Hg. All meteorites studied here have however isotopically light Hg (δ202Hg = ∼-7 to -1) relative to the Earth's average crustal values, which could suggest that the Earth has lost a significant fraction of its primordial Hg. However, the late accretion of carbonaceous chondritic material on the order of ∼2%, which has been suggested to account for the water, carbon, nitrogen and noble gas inventories of the Earth, can also contribute most or all of the Earth's current Hg budget. In this case, the isotopically heavy Hg of the Earth's crust would have to be the result of isotopic fractionation between surface and deep-Earth reservoirs.

  17. Fluorescent profiling of modular biosynthetic enzymes by complementary metabolic and activity based probes.

    Meier, Jordan L; Mercer, Andrew C; Burkart, Michael D

    2008-04-23

    The study of the enzymes responsible for natural product biosynthesis has proven a valuable source of new enzymatic activities and been applied to a number of biotechnology applications. Protein profiling could prove highly complementary to genetics based approaches by allowing us to understand the activity, transcriptional control, and post-translational modification of these enzymes in their native and dynamic proteomic environments. Here we present a method for the fluorescent profiling of PKS, NRPS, and FAS multidomain modular synthases in their whole proteomes using complementary metabolic and activity based probes. After first examining the reactivity of these activity based probes with a variety of purified recombinant PKS, NRPS, and FAS enzymes in vitro, we apply this duel labeling strategy to the analysis of modular synthases in a human breast cancer cell line and two strains of the natural product producer Bacillus subtilis. Collectively, these studies demonstrate that complementary protein profiling approaches can prove highly useful in the identification and assignment of inhibitor specificity and domain structure of these modular biosynthetic enzymes. PMID:18376827

  18. Dynamic transcription factor activity profiles reveal key regulatory interactions during megakaryocytic and erythroid differentiation.

    Duncan, Mark T; Shin, Seungjin; Wu, Jia J; Mays, Zachary; Weng, Stanley; Bagheri, Neda; Miller, William M; Shea, Lonnie D

    2014-10-01

    The directed differentiation toward erythroid (E) or megakaryocytic (MK) lineages by the MK-E progenitor (MEP) could enhance the ex vivo generation of red blood cells and platelets for therapeutic transfusions. The lineage choice at the MEP bifurcation is controlled in large part by activity within the intracellular signal transduction network, the output of which determines the activity of transcription factors (TFs) and ultimately gene expression. Although many TFs have been implicated, E or MK differentiation is a complex process requiring multiple days, and the dynamics of TF activities during commitment and terminal maturation are relatively unexplored. Herein, we applied a living cell array for the large-scale, dynamic quantification of TF activities during MEP bifurcation. A panel of hematopoietic TFs (GATA-1, GATA-2, SCL/TAL1, FLI-1, NF-E2, PU.1, c-Myb) was characterized during E and MK differentiation of bipotent K562 cells. Dynamic TF activity profiles associated with differentiation towards each lineage were identified, and validated with previous reports. From these activity profiles, we show that GATA-1 is an important hub during early hemin- and PMA-induced differentiation, and reveal several characteristic TF interactions for E and MK differentiation that confirm regulatory mechanisms documented in the literature. Additionally, we highlight several novel TF interactions at various stages of E and MK differentiation. Furthermore, we investigated the mechanism by which nicotinamide (NIC) promoted terminal MK maturation using an MK-committed cell line, CHRF-288-11 (CHRF). Concomitant with its enhancement of ploidy, NIC strongly enhanced the activity of three TFs with known involvement in terminal MK maturation: FLI-1, NF-E2, and p53. Dynamic profiling of TF activity represents a novel tool to complement traditional assays focused on mRNA and protein expression levels to understand progenitor cell differentiation. PMID:24853077

  19. Structure-Dependent Immune Modulatory Activity of Protegrin-1 Analogs

    Susu M. Zughaier

    2014-11-01

    Full Text Available Protegrins are porcine antimicrobial peptides (AMPs that belong to the cathelicidin family of host defense peptides. Protegrin-1 (PG-1, the most investigated member of the protegrin family, is an arginine-rich peptide consisting of 18 amino acid residues, its main chain adopting a β-hairpin structure that is linked by two disulfide bridges. We report on the immune modulatory activity of PG-1 and its analogs in neutralizing bacterial endotoxin and capsular polysaccharides, consequently inhibiting inflammatory mediators’ release from macrophages. We demonstrate that the β-hairpin structure motif stabilized with at least one disulfide bridge is a prerequisite for the immune modulatory activity of this type of AMP.

  20. Length and activation dependent variations in muscle shear wave speed

    Muscle stiffness is known to vary as a result of a variety of disease states, yet current clinical methods for quantifying muscle stiffness have limitations including cost and availability. We investigated the capability of shear wave elastography (SWE) to measure variations in gastrocnemius shear wave speed induced via active contraction and passive stretch. Ten healthy young adults were tested. Shear wave speeds were measured using a SWE transducer positioned over the medial gastrocnemius at ankle angles ranging from maximum dorsiflexion to maximum plantarflexion. Shear wave speeds were also measured during voluntary plantarflexor contractions at a fixed ankle angle. Average shear wave speed increased significantly from 2.6 to 5.6 m s–1 with passive dorsiflexion and the knee in an extended posture, but did not vary with dorsiflexion when the gastrocnemius was shortened in a flexed knee posture. During active contractions, shear wave speed monotonically varied with the net ankle moment generated, reaching 8.3 m s–1 in the maximally contracted condition. There was a linear correlation between shear wave speed and net ankle moment in both the active and passive conditions; however, the slope of this linear relationship was significantly steeper for the data collected during passive loading conditions. The results show that SWE is a promising approach for quantitatively assessing changes in mechanical muscle loading. However, the differential effect of active and passive loading on shear wave speed makes it important to carefully consider the relevant loading conditions in which to use SWE to characterize in vivo muscle properties. (paper)

  1. A Memristor SPICE Model Accounting for Synaptic Activity Dependence

    Qingjiang Li; Alexander Serb; Themistoklis Prodromakis; Hui Xu

    2015-01-01

    In this work, we propose a new memristor SPICE model that accounts for the typical synaptic characteristics that have been previously demonstrated with practical memristive devices. We show that this model could account for both volatile and non-volatile memristance changes under distinct stimuli. We then demonstrate that our model is capable of supporting typical STDP with simple non-overlapping digital pulse pairs. Finally, we investigate the capability of our model to simulate the activity...

  2. Anthropometric profile and habits of physical activity of a scho ol students Mapuches rural Temuco, Chile

    Pablo Antonio Valdés-Badilla

    2015-04-01

    Full Text Available Introduction: The nutritional status of children can be a predictor of health in adulthood element, the Mapuche population has a non-Mapuche population that increased prevalence of obesity in Chile. The aim of this study was to determine the anthropometric profile and physical activity habits of Mapuche students of a particular charter school in the rural of Temuco city.Material and Methods: The design is not experimental, descriptive, transversal, with a quantitative approach. The sample included all students of the educational establishment Mapuches (n=23, in both sexes. He underwent anthropometric assessment ISAK and total time physical activity was estimated by the International Physical Activity Questionnaire, short version in Spanish (IPAQ-A. To correlate the variables a partial correlation was used.Results: The students average about 35.4% of fat mass, muscle mass 34.1%, 11.4% of residual mass, 12% of bone mass, 7% of residual mass and somatotype 4.9–5.1–1.8 that meso-endomorph classified as balanced. Regarding the total time physical activity, students reach 2225.9 minutes/week, your energy expenditure is 9592.1 (METs/min/week and stay seated equals 228.6 minutes per week, finally negative correlation was found between BMI and total time of physical activity.Conclusions: The students have a mostly standard anthropometric profile, but with a troubling obesity rate. His activity level is high, placing them as active subjects according to normative tables.

  3. TLAPrfl: Package for calculation of depth profile for thin layer activation. Summary of contents

    TLAPrfl computer code package provides an easy means of calculating depth profiles of radioactivity induced by incident beam of charge particles in target material. The technique is commonly referred to as Thin Layer Activation (TLA). TLA profiles can be calculated for 35 reactions leading to specific activity induced by p, d, 3He or α with incident energy up to 44 MeV on 12 isotopes and elements. IonStop code for calculation of ion energy loss characteristic in medium is also included. A diskette with TLAPrfl code package is available upon request, cost-free, from the IAEA Nuclear Data Section. Users with access to Internet may download TLAPrfl.zip file (379 KB) from http://www-nds.iaea.or.at/reports/data/tlaprfl.zip. (author)

  4. relA-dependent RNA polymerase activity in Escherichia coli.

    Ryals, J; Bremer, H

    1982-01-01

    Parameters relating to RNA synthesis were measured after a temperature shift from 30 to 42 degrees C, in a relA+ and relA- isogenic pair of Escherichia coli strains containing a temperature-sensitive valyl tRNA synthetase. The following results were obtained: (i) the rRNA chain growth rate increased 2-fold in both strains; (ii) newly synthesized rRNA became unstable in both strains; (iii) the stable RNA gene activity (rRNA and tRNA, measured as stable RNA synthesis rate relative to the total ...

  5. Effect of increased yeast alcohol acetyltransferase activity on flavor profiles of wine and distillates.

    Lilly, M; Lambrechts, M G; Pretorius, I S

    2000-02-01

    The distinctive flavor of wine, brandy, and other grape-derived alcoholic beverages is affected by many compounds, including esters produced during alcoholic fermentation. The characteristic fruity odors of the fermentation bouquet are primarily due to a mixture of hexyl acetate, ethyl caproate (apple-like aroma), iso-amyl acetate (banana-like aroma), ethyl caprylate (apple-like aroma), and 2-phenylethyl acetate (fruity, flowery flavor with a honey note). The objective of this study was to investigate the feasibility of improving the aroma of wine and distillates by overexpressing one of the endogenous yeast genes that controls acetate ester production during fermentation. The synthesis of acetate esters by the wine yeast Saccharomyces cerevisiae during fermentation is ascribed to at least three acetyltransferase activities, namely, alcohol acetyltransferase (AAT), ethanol acetyltransferase, and iso-amyl AAT. To investigate the effect of increased AAT activity on the sensory quality of Chenin blanc wines and distillates from Colombar base wines, we have overexpressed the alcohol acetyltransferase gene (ATF1) of S. cerevisiae. The ATF1 gene, located on chromosome XV, was cloned from a widely used commercial wine yeast strain of S. cerevisiae, VIN13, and placed under the control of the constitutive yeast phosphoglycerate kinase gene (PGK1) promoter and terminator. Chromoblot analysis confirmed the integration of the modified copy of ATF1 into the genome of three commercial wine yeast strains (VIN7, VIN13, and WE228). Northern blot analysis indicated constitutive expression of ATF1 at high levels in these yeast transformants. The levels of ethyl acetate, iso-amyl acetate, and 2-phenylethyl acetate increased 3- to 10-fold, 3.8- to 12-fold, and 2- to 10-fold, respectively, depending on the fermentation temperature, cultivar, and yeast strain used. The concentrations of ethyl caprate, ethyl caprylate, and hexyl acetate only showed minor changes, whereas the acetic acid

  6. Profiling Physical Activity, Diet, Screen and Sleep Habits in Portuguese Children

    Sara Pereira; Katzmarzyk, Peter T.; Thayse Natacha Gomes; Alessandra Borges; Daniel Santos; Michele Souza; dos Santos, Fernanda K.; Chaves, Raquel N.; Champagne, Catherine M.; Barreira, Tiago V.; Maia, José A. R.

    2015-01-01

    Obesity in children is partly due to unhealthy lifestyle behaviours, e.g., sedentary activity and poor dietary choices. This trend has been seen globally. To determine the extent of these behaviours in a Portuguese population of children, 686 children 9.5 to 10.5 years of age were studied. Our aims were to: (1) describe profiles of children’s lifestyle behaviours; (2) identify behaviour pattern classes; and (3) estimate combined effects of individual/ socio-demographic characteristics in pred...

  7. Evaluation of Activation Energy (Ea) Profiles of Nanostructured Alumina Polycarbonate Composite Insulation Materials

    Sudha L. K.; Sukumar Roy; K. Uma Rao

    2014-01-01

    This paper focuses enhancement of the electrical insulation properties of commercial polycarbonate using nanostructured alumina as an additive material. Various polycarbonate composites have been prepared by varying the level of additive material and DC conductivity in presence of oxygen of the derived composite materials has been measured in which activation energy (Ea) profiles of the composites have been evaluated. Results show that the incorporation of additive significantly reduces the E...

  8. Polyphenolic Profile, Antioxidant and Anti-Inflammatory Activity of Eastern Teaberry (Gaultheria procumbens L.) Leaf Extracts

    Piotr Michel; Anna Dobrowolska; Agnieszka Kicel; Aleksandra Owczarek; Agnieszka Bazylko; Sebastian Granica; Piwowarski, Jakub P.; Olszewska, Monika A.

    2014-01-01

    Dry leaf extracts of eastern teaberry (Gaultheria procumbens L.) were evaluated as a source of bioactive phytocompounds through systematic activity testing and phytochemical profiling. The antioxidant efficiency was tested using five complementary in vitro models (DPPH; FRAP; linoleic acid (LA) peroxidation assay; O2•− and H2O2 scavenging tests) in parallel with standard antioxidants. The 75% methanol extract and its diethyl ether, ethyl acetate (EAF), n-butanol and water fractions exhibited ...

  9. Effects of Orange Juice and Hesperetin on Serum Paraoxonase Activity and Lipid Profile in Hyperuricemic Rats

    Fatemeh Haidari; Mohammad-Reza Rashidi; Majid Mohammad-Shahi

    2012-01-01

    Introduction: Hypouricemic, antioxidant and xanthine oxidase inhibitory effects of orange juice and hesperetin have been already indicated. The objective of this study was to investigate the effects of orange juice and hesperetin on paraoxonase and arylesterase activity and lipid profile of hyperuricemic rats. Methods: Forty eight male Wistar rats were divided into 8 equal groups of healthy control, healthy+orange juice, healthy+hesperetin, healthy+allopurinol, hyperuricemic control, hyperuri...

  10. Cytokinin and Auxin Display Distinct but Interconnected Distribution and Signaling Profiles to Stimulate Cambial Activity.

    Immanen, Juha; Nieminen, Kaisa; Smolander, Olli-Pekka; Kojima, Mikiko; Alonso Serra, Juan; Koskinen, Patrik; Zhang, Jing; Elo, Annakaisa; Mähönen, Ari Pekka; Street, Nathaniel; Bhalerao, Rishikesh P; Paulin, Lars; Auvinen, Petri; Sakakibara, Hitoshi; Helariutta, Ykä

    2016-08-01

    Despite the crucial roles of phytohormones in plant development, comparison of the exact distribution profiles of different hormones within plant meristems has thus far remained scarce. Vascular cambium, a wide lateral meristem with an extensive developmental zonation, provides an optimal system for hormonal and genetic profiling. By taking advantage of this spatial resolution, we show here that two major phytohormones, cytokinin and auxin, display different yet partially overlapping distribution profiles across the cambium. In contrast to auxin, which has its highest concentration in the actively dividing cambial cells, cytokinins peak in the developing phloem tissue of a Populus trichocarpa stem. Gene expression patterns of cytokinin biosynthetic and signaling genes coincided with this hormonal gradient. To explore the functional significance of cytokinin signaling for cambial development, we engineered transgenic Populus tremula × tremuloides trees with an elevated cytokinin biosynthesis level. Confirming that cytokinins function as major regulators of cambial activity, these trees displayed stimulated cambial cell division activity resulting in dramatically increased (up to 80% in dry weight) production of the lignocellulosic trunk biomass. To connect the increased growth to hormonal status, we analyzed the hormone distribution and genome-wide gene expression profiles in unprecedentedly high resolution across the cambial zone. Interestingly, in addition to showing an elevated cambial cytokinin content and signaling level, the cambial auxin concentration and auxin-responsive gene expression were also increased in the transgenic trees. Our results indicate that cytokinin signaling specifies meristematic activity through a graded distribution that influences the amplitude of the cambial auxin gradient. PMID:27426519