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Sample records for selective pressure mediate

  1. Quantifying Selection Pressure

    NARCIS (Netherlands)

    Haasdijk, Evert; Heinerman, J.V.

    2017-01-01

    Selection is an essential component of any evolutionary systemand analysing this fundamental force in evolution can provide relevant insights into the evolutionary development of a population. The 1990s and early 2000s saw a substantial number of publications that investigated selection pressure

  2. Selective A2A receptor antagonist prevents microglia-mediated neuroinflammation and protects retinal ganglion cells from high intraocular pressure-induced transient ischemic injury.

    Science.gov (United States)

    Madeira, Maria H; Boia, Raquel; Elvas, Filipe; Martins, Tiago; Cunha, Rodrigo A; Ambrósio, António Francisco; Santiago, Ana Raquel

    2016-03-01

    Glaucoma is a leading cause of vision loss and blindness worldwide, characterized by chronic and progressive neuronal loss. Reactive microglial cells have been recognized as a neuropathologic feature, contributing to local inflammation and retinal neurodegeneration. In a recent in vitro work (organotypic cultures), we demonstrated that blockade of adenosine A2A receptor (A2AR) prevents the neuroinflammatory response and affords protection to retinal ganglion cells (RGCs) against exposure to elevated hydrostatic pressure (EHP), to mimic elevated intraocular pressure (IOP), the main risk factor for glaucoma development. Herein, we investigated whether a selective A2AR antagonist (SCH 58261) could modulate retinal microglia reactivity and their inflammatory response. Furthermore, we took advantage of the high IOP-induced transient ischemia (ischemia-reperfusion, I-R) animal model to evaluate the protective role of A2AR blockade in the control of retinal neuroinflammation and neurodegeneration. Primary microglial cell cultures were challenged either with lipopolysaccharide or with EHP, in the presence or absence of A2AR antagonist SCH 58261 (50 nM). In addition, I-R injury was induced in adult Wistar rats after intravitreal administration of SCH 58261 (100 nM, 5 μL). Our results showed that SCH 58261 attenuated microglia reactivity and the increased expression and release of proinflammatory cytokines. Moreover, intravitreal administration of SCH 58261 prevented I-R-induced cell death and RGC loss, by controlling microglial-mediated neuroinflammatory response. These results prompt the proposal that A2AR blockade may have great potential in the management of retinal neurodegenerative diseases characterized by microglia reactivity and RGC death, such as glaucoma and ischemic diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Pressure-mediated doping in graphene.

    Science.gov (United States)

    Nicolle, Jimmy; Machon, Denis; Poncharal, Philippe; Pierre-Louis, Olivier; San-Miguel, Alfonso

    2011-09-14

    Exfoliated graphene and few layer graphene samples supported on SiO(2) have been studied by Raman spectroscopy at high pressure. For samples immersed on a alcohol mixture, an electron transfer of ∂n/∂P ∼ 8 × 10(12) cm(-2) GPa(-1) is observed for monolayer and bilayer graphene, leading to giant doping values of n ∼ 6 × 10(13) cm(-2) at the maximum pressure of 7 GPa. Three independent and consistent proofs of the doping process are obtained from (i) the evolution of the Raman G-band to 2D-band intensity ratio, (ii) the pressure coefficient of the G-band frequency, and (iii) the 2D band components splitting in the case of the bilayer sample. The charge transfer phenomena is absent for trilayer samples and for samples immersed in argon or nitrogen. We also show that a phase transition from a 2D biaxial strain response, resulting from the substrate drag upon volume reduction, to a 3D hydrostatic compression takes place when going from the bilayer to the trilayer sample. By model calculations we relate this transition to the unbinding of the graphene-SiO(2) system when increasing the number of graphene layers and as function of the surface roughness parameters. We propose that the formation of silanol groups on the SiO(2) substrate allows for a capacitance-induced substrate-mediated charge transfer.

  4. Pressure ulcer grading and appropriate equipment selection.

    Science.gov (United States)

    Charlton, Sarah

    2014-08-12

    This article explores the process and rationale for designing a poster to support community nurses in selecting appropriate pressure-relieving equipment based on accurate risk assessment and correct pressure ulcer grading. The project was prompted by the requirement to update community nurses' knowledge and ensure pressure-relieving equipment selection was evidence-based and not reliant on personal preference. The 2012 NHS Midlands and East 'Stop the pressure' campaign provided community nurses with a framework for pressure ulcer prevention and management. The attention to support surfaces highlighted the need for appropriate equipment. However the tissue viability team found that the introduction of this pathway alone did not help with the practical issues of appropriate equipment selection. The poster was designed with consideration as to how adults learn, and by looking to the Plan, Do, Study, Act (PDSA) cycle. This provided the framework for enabling new ideas and changes to practice to be tested on a small scale before full implementation.

  5. Selecting a model of supersymmetry breaking mediation

    International Nuclear Information System (INIS)

    AbdusSalam, S. S.; Allanach, B. C.; Dolan, M. J.; Feroz, F.; Hobson, M. P.

    2009-01-01

    We study the problem of selecting between different mechanisms of supersymmetry breaking in the minimal supersymmetric standard model using current data. We evaluate the Bayesian evidence of four supersymmetry breaking scenarios: mSUGRA, mGMSB, mAMSB, and moduli mediation. The results show a strong dependence on the dark matter assumption. Using the inferred cosmological relic density as an upper bound, minimal anomaly mediation is at least moderately favored over the CMSSM. Our fits also indicate that evidence for a positive sign of the μ parameter is moderate at best. We present constraints on the anomaly and gauge mediated parameter spaces and some previously unexplored aspects of the dark matter phenomenology of the moduli mediation scenario. We use sparticle searches, indirect observables and dark matter observables in the global fit and quantify robustness with respect to prior choice. We quantify how much information is contained within each constraint.

  6. Selection pressure in alternative reading frames.

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    Katharina Mir

    Full Text Available Overlapping genes are two protein-coding sequences sharing a significant part of the same DNA locus in different reading frames. Although in recent times an increasing number of examples have been found in bacteria the underlying mechanisms of their evolution are unknown. In this work we explore how selective pressure in a protein-coding sequence influences its overlapping genes in alternative reading frames. We model evolution using a time-continuous Markov process and derive the corresponding model for the remaining frames to quantify selection pressure and genetic noise. Our findings lead to the presumption that, once information is embedded in the reverse reading frame -2 (relative to the mother gene in +1 purifying selection in the protein-coding reading frame automatically protects the sequences in both frames. We also found that this coincides with the fact that the genetic noise measured using the conditional entropy is minimal in frame -2 under selection in the coding frame.

  7. HIV-1 adaptation to NK cell-mediated immune pressure

    DEFF Research Database (Denmark)

    Elemans, Marjet; Boelen, Lies; Rasmussen, Michael

    2017-01-01

    The observation, by Alter et al., of the enrichment of NK cell “escape” variants in individuals carrying certain Killer-cell Immunoglobulin-like Receptor (KIR) genes is compelling evidence that natural killer (NK) cells exert selection pressure on HIV-1. Alter et al hypothesise that variant pepti...

  8. Biosurfactant Mediated Biosynthesis of Selected Metallic Nanoparticles

    Science.gov (United States)

    Płaza, Grażyna A.; Chojniak, Joanna; Banat, Ibrahim M.

    2014-01-01

    Developing a reliable experimental protocol for the synthesis of nanomaterials is one of the challenging topics in current nanotechnology particularly in the context of the recent drive to promote green technologies in their synthesis. The increasing need to develop clean, nontoxic and environmentally safe production processes for nanoparticles to reduce environmental impact, minimize waste and increase energy efficiency has become essential in this field. Consequently, recent studies on the use of microorganisms in the synthesis of selected nanoparticles are gaining increased interest as they represent an exciting area of research with considerable development potential. Microorganisms are known to be capable of synthesizing inorganic molecules that are deposited either intra- or extracellularly. This review presents a brief overview of current research on the use of biosurfactants in the biosynthesis of selected metallic nanoparticles and their potential importance. PMID:25110864

  9. Biosurfactant Mediated Biosynthesis of Selected Metallic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Grażyna A. Płaza

    2014-08-01

    Full Text Available Developing a reliable experimental protocol for the synthesis of nanomaterials is one of the challenging topics in current nanotechnology particularly in the context of the recent drive to promote green technologies in their synthesis. The increasing need to develop clean, nontoxic and environmentally safe production processes for nanoparticles to reduce environmental impact, minimize waste and increase energy efficiency has become essential in this field. Consequently, recent studies on the use of microorganisms in the synthesis of selected nanoparticles are gaining increased interest as they represent an exciting area of research with considerable development potential. Microorganisms are known to be capable of synthesizing inorganic molecules that are deposited either intra- or extracellularly. This review presents a brief overview of current research on the use of biosurfactants in the biosynthesis of selected metallic nanoparticles and their potential importance.

  10. Potent and selective mediators of cholesterol efflux

    Energy Technology Data Exchange (ETDEWEB)

    Bielicki, John K; Johansson, Jan

    2015-03-24

    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  11. Selectivity of oxymetazoline for urethral pressure vs blood pressure in the anaesthetized female rabbit.

    Science.gov (United States)

    Modiri, A R; Fredrickson, M G; Gillberg, P G; Alberts, P

    2000-06-01

    The aim of this study was to test alpha-adrenergic reference agonists for tissue selectivity in the urethra and to pharmacologically characterize the functional alpha-adrenoceptor type of the female rabbit urethra in vivo. The effect of alpha-adrenergic agonists and antagonists on the urethral pressure was compared with that on blood pressure and heart rate measured simultaneously in the anaesthetized female rabbit. Oxymetazoline, NS-49, phenylephrine and phenylpropanolamine enhanced the urethral pressure in a dose-dependent manner. Phenylephrine and phenylpropanolamine also enhanced the blood pressure with significantly lower ED50 (dose that gives half of the maximal enhancing effect) values than for the urethral pressure. This was in contrast to oxymetazoline and NS-49. The ED50 values for oxymetazoline on urethral pressure, and systolic and diastolic blood pressure were 0.00067, 0.0030 and 0.0020 mg/kg, respectively. The ED50 values for NS-49 on urethral pressure, and systolic and diastolic blood pressure were 0.019, 0.21 and 0.18 mg/kg, respectively. Clonidine and UK 14,304 had no effect on urethral or blood pressure. The oxymetazoline-evoked increase in urethral pressure was inhibited by WB-4101 with an ID50 (dose that gives half of the inhibitory effect) significantly lower than that for rauwolscine. The results suggest that in the female rabbit in vivo activation of alpha1-adrenoceptors increased the urethral pressure. Phenylephrine and phenylpropanolamine, in contrast to oxymetazoline and NS-49, selectively enhanced blood pressure as compared with urethral pressure. Provided that the present results also have validity in humans, it would seem possible to develop urethra-selective drugs for treatment of stress incontinence with few or no cardiovascular side-effects.

  12. Unravelling anisogamy: egg size and ejaculate size mediate selection on morphology in free-swimming sperm.

    Science.gov (United States)

    Monro, Keyne; Marshall, Dustin J

    2016-07-13

    Gamete dimorphism (anisogamy) defines the sexes in most multicellular organisms. Theoretical explanations for its maintenance usually emphasize the size-related selection pressures of sperm competition and zygote survival, assuming that fertilization of all eggs precludes selection for phenotypes that enhance fertility. In external fertilizers, however, fertilization is often incomplete due to sperm limitation, and the risk of polyspermy weakens the advantage of high sperm numbers that is predicted to limit sperm size, allowing alternative selection pressures to target free-swimming sperm. We asked whether egg size and ejaculate size mediate selection on the free-swimming sperm of Galeolaria caespitosa, a marine tubeworm with external fertilization, by comparing relationships between sperm morphology and male fertility across manipulations of egg size and sperm density. Our results suggest that selection pressures exerted by these factors may aid the maintenance of anisogamy in external fertilizers by limiting the adaptive value of larger sperm in the absence of competition. In doing so, our study offers a more complete explanation for the stability of anisogamy across the range of sperm environments typical of this mating system and identifies new potential for the sexes to coevolve via mutual selection pressures exerted by gametes at fertilization. © 2016 The Author(s).

  13. Selection Demands and Working Memory Mediate Interference during Naming

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    Julie W Hughes

    2015-05-01

    Analyzing RTs, we replicated previous SI effects in BCN in healthy subjects and patients (reported effects’ p’s < .05. Subjects responded more slowly to items in semantically related vs. unrelated groups, and this interference increased across cycles (evidence of increasing selection demands; Figures 1a/c. Indicative of WM, healthy subjects were faster to name items as the number of unrelated items to be named (i.e., remembered decreased. However, this was attenuated by selection demand, as there was no decrease in RTs across repeated related items (Figure 1b. Converging evidence from patients demonstrated more impaired selection capacity produced increasingly slower RTs across item positions within the related condition (high selection demand (Figure 1d. Larger WM capacity (rhyme probe but not category probe, p = .54 produced increasingly faster RTs across items positions in the unrelated condition (low selection demand (Figure 1e. Together, these findings suggest that both selection demand and phonological WM processes mediate interference during naming.

  14. Contrasted patterns of selective pressure in three recent paralogous gene pairs in the Medicago genus (L.

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    Ho-Huu Joan

    2012-10-01

    Full Text Available Abstract Background Gene duplications are a molecular mechanism potentially mediating generation of functional novelty. However, the probabilities of maintenance and functional divergence of duplicated genes are shaped by selective pressures acting on gene copies immediately after the duplication event. The ratio of non-synonymous to synonymous substitution rates in protein-coding sequences provides a means to investigate selective pressures based on genic sequences. Three molecular signatures can reveal early stages of functional divergence between gene copies: change in the level of purifying selection between paralogous genes, occurrence of positive selection, and transient relaxed purifying selection following gene duplication. We studied three pairs of genes that are known to be involved in an interaction with symbiotic bacteria and were recently duplicated in the history of the Medicago genus (Fabaceae. We sequenced two pairs of polygalacturonase genes (Pg11-Pg3 and Pg11a-Pg11c and one pair of auxine transporter-like genes (Lax2-Lax4 in 17 species belonging to the Medicago genus, and sought for molecular signatures of differentiation between copies. Results Selective histories revealed by these three signatures of molecular differentiation were found to be markedly different between each pair of paralogs. We found sites under positive selection in the Pg11 paralogs while Pg3 has mainly evolved under purifying selection. The most recent paralogs examined Pg11a and Pg11c, are both undergoing positive selection and might be acquiring new functions. Lax2 and Lax4 paralogs are both under strong purifying selection, but still underwent a temporary relaxation of purifying selection immediately after duplication. Conclusions This study illustrates the variety of selective pressures undergone by duplicated genes and the effect of age of the duplication. We found that relaxation of selective constraints immediately after duplication might promote

  15. Novel mutations in Marburg virus glycoprotein associated with viral evasion from antibody mediated immune pressure.

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    Kajihara, Masahiro; Nakayama, Eri; Marzi, Andrea; Igarashi, Manabu; Feldmann, Heinz; Takada, Ayato

    2013-04-01

    Marburg virus (MARV) and Ebola virus, members of the family Filoviridae, cause lethal haemorrhagic fever in humans and non-human primates. Although the outbreaks are concentrated mainly in Central Africa, these viruses are potential agents of imported infectious diseases and bioterrorism in non-African countries. Recent studies demonstrated that non-human primates passively immunized with virus-specific antibodies were successfully protected against fatal filovirus infection, highlighting the important role of antibodies in protective immunity for this disease. However, the mechanisms underlying potential evasion from antibody mediated immune pressure are not well understood. To analyse possible mutations involved in immune evasion in the MARV envelope glycoprotein (GP) which is the major target of protective antibodies, we selected escape mutants of recombinant vesicular stomatitis virus (rVSV) expressing MARV GP (rVSVΔG/MARVGP) by using two GP-specific mAbs, AGP127-8 and MGP72-17, which have been previously shown to inhibit MARV budding. Interestingly, several rVSVΔG/MARVGP variants escaping from the mAb pressure-acquired amino acid substitutions in the furin-cleavage site rather than in the mAb-specific epitopes, suggesting that these epitopes are recessed, not exposed on the uncleaved GP molecule, and therefore inaccessible to the mAbs. More surprisingly, some variants escaping mAb MGP72-17 lacked a large proportion of the mucin-like region of GP, indicating that these mutants efficiently escaped the selective pressure by deleting the mucin-like region including the mAb-specific epitope. Our data demonstrate that MARV GP possesses the potential to evade antibody mediated immune pressure due to extraordinary structural flexibility and variability.

  16. Competitive Pressure, Selection and Investments in Development and Fundamental Research

    NARCIS (Netherlands)

    Boone, J.

    1998-01-01

    This paper analyses the effects of competitive pressure on a firm's incentives to undertake both fundamental research and development. It presents a new framework incorporating the selection effect of product market competition, the Schumpeterian argument for monopoly power, the Nickell/Porter

  17. Quantifying Selective Pressures Driving Bacterial Evolution Using Lineage Analysis

    Science.gov (United States)

    Lambert, Guillaume; Kussell, Edo

    2015-01-01

    Organisms use a variety of strategies to adapt to their environments and maximize long-term growth potential, but quantitative characterization of the benefits conferred by the use of such strategies, as well as their impact on the whole population's rate of growth, remains challenging. Here, we use a path-integral framework that describes how selection acts on lineages—i.e., the life histories of individuals and their ancestors—to demonstrate that lineage-based measurements can be used to quantify the selective pressures acting on a population. We apply this analysis to Escherichia coli bacteria exposed to cyclical treatments of carbenicillin, an antibiotic that interferes with cell-wall synthesis and affects cells in an age-dependent manner. While the extensive characterization of the life history of thousands of cells is necessary to accurately extract the age-dependent selective pressures caused by carbenicillin, the same measurement can be recapitulated using lineage-based statistics of a single surviving cell. Population-wide evolutionary pressures can be extracted from the properties of the surviving lineages within a population, providing an alternative and efficient procedure to quantify the evolutionary forces acting on a population. Importantly, this approach is not limited to age-dependent selection, and the framework can be generalized to detect signatures of other trait-specific selection using lineage-based measurements. Our results establish a powerful way to study the evolutionary dynamics of life under selection and may be broadly useful in elucidating selective pressures driving the emergence of antibiotic resistance and the evolution of survival strategies in biological systems.

  18. Selective aerobic oxidation mediated by TiO(2) photocatalysis.

    Science.gov (United States)

    Lang, Xianjun; Ma, Wanhong; Chen, Chuncheng; Ji, Hongwei; Zhao, Jincai

    2014-02-18

    TiO2 is one of the most studied metal oxide photocatalysts and has unparal-leled efficiency and stability. This cheap, abundant, and non-toxic material has the potential to address future environmental and energy concerns. Understanding about the photoinduced interfacial redox events on TiO2 could have profound effect on the degradation of organic pollutants, splitting of H2O into H2 and O2, and selective redox organic transformations. Scientists traditionally accept that for a semiconductor photocatalyst such as TiO2 under the illumination of light with energy larger than its band gap, two photocarriers will be created to carry out their independent reduction and oxidation processes. However, our recent discoveries indicate that it is the concerted rather than independent effect of both photocarriers of valence band hole (hvb(+)) and conduction band electron (ecb(-)) that dictate the product formation during interfacial oxidation event mediated by TiO2 photocatalysis. In this Account, we describe our recent findings on the selective oxidation of organic substrates with O2 mediated by TiO2 photocatalysis. The transfer of O-atoms from O2 to the corresponding products dominates the selective oxidation of alcohols, amines, and alkanes mediated by TiO2 photocatalysis. We ascribe this to the concerted effect of both hvb(+) and ecb(-) of TiO2 in contribution to the oxidation products. These findings imply that O2 plays a unique role in its transfer into the products rather than independent role of ecb(-) scavenger. More importantly, ecb(-) plays a crucial role to ensure the high selectivity for the oxygenation of organic substrates. We can also use the half reactions such as those of the conduction band electron of TiO2 for efficient oxidation reactions with O2. To this end, efficient selective oxidation of organic substrates such as alcohols, amines, and aromatic alkanes with O2 mediated by TiO2 photocatalysis under visible light irradiation has been achieved. In

  19. HLA-B*57 Micropolymorphism shapes HLA allele-specific epitope immunogenicity, selection pressure, and HIV immune control

    DEFF Research Database (Denmark)

    Kløverpris, Henrik Nyhus; Buus, Anette Stryhn; van der Stok, Mary

    2012-01-01

    of HIV, we undertook, in a study of >1,000 C-clade-infected subjects, a comprehensive analysis of the epitopes presented by these 3 alleles and of the selection pressure imposed on HIV by each response. In contrast to previous studies, we show that each of these three HLA alleles is characterized both...... by unique CD8(+) T-cell specificities and by clear-cut differences in selection pressure imposed on the virus by those responses. These studies comprehensively define for the first time the CD8(+) T-cell responses and immune selection pressures for which these protective alleles are responsible....... These findings are consistent with HLA class I alleles mediating effective immune control of HIV through the number of p24 Gag-specific CD8(+) T-cell responses generated that can drive significant selection pressure on the virus....

  20. VESPA: Very large-scale Evolutionary and Selective Pressure Analyses

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    Andrew E. Webb

    2017-06-01

    Full Text Available Background Large-scale molecular evolutionary analyses of protein coding sequences requires a number of preparatory inter-related steps from finding gene families, to generating alignments and phylogenetic trees and assessing selective pressure variation. Each phase of these analyses can represent significant challenges, particularly when working with entire proteomes (all protein coding sequences in a genome from a large number of species. Methods We present VESPA, software capable of automating a selective pressure analysis using codeML in addition to the preparatory analyses and summary statistics. VESPA is written in python and Perl and is designed to run within a UNIX environment. Results We have benchmarked VESPA and our results show that the method is consistent, performs well on both large scale and smaller scale datasets, and produces results in line with previously published datasets. Discussion Large-scale gene family identification, sequence alignment, and phylogeny reconstruction are all important aspects of large-scale molecular evolutionary analyses. VESPA provides flexible software for simplifying these processes along with downstream selective pressure variation analyses. The software automatically interprets results from codeML and produces simplified summary files to assist the user in better understanding the results. VESPA may be found at the following website: http://www.mol-evol.org/VESPA.

  1. Positive-negative-selection-mediated gene targeting in rice

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    Zenpei eShimatani

    2015-01-01

    Full Text Available Gene targeting (GT refers to the designed modification of genomic sequence(s through homologous recombination (HR. GT is a powerful tool both for the study of gene function and for molecular breeding. However, in transformation of higher plants, non-homologous end joining (NHEJ occurs overwhelmingly in somatic cells, masking HR-mediated GT. Positive-negative selection (PNS is an approach for finding HR-mediated GT events because it can eliminate NHEJ effectively by expression of a negative-selection marker gene. In rice—a major crop worldwide—reproducible PNS-mediated GT of endogenous genes has now been successfully achieved. The procedure is based on strong PNS using diphtheria toxin A-fragment as a negative marker, and has succeeded in the directed modification of several endogenous rice genes in various ways. In addition to gene knock-outs and knock-ins, a nucleotide substitution in a target gene was also achieved recently. This review presents a summary of the development of the rice PNS system, highlighting its advantages. Different types of gene modification and gene editing aimed at developing new plant breeding technology (NPBT based on PNS are discussed.

  2. Chitosan-mediated and spatially selective electrodeposition of nanoscale particles.

    Science.gov (United States)

    Wu, Li-Qun; Lee, Kyuyong; Wang, Xiang; English, Douglas S; Losert, Wolfgang; Payne, Gregory F

    2005-04-12

    Nanoscale particles offer a variety of interesting properties, and there is growing interest in their assembly into higher ordered structures. We report that the pH-responsive aminopolysaccharide chitosan can mediate the electrodeposition of model nanoparticles. Chitosan is known to electrodeposit at the cathode surface in response to a high localized pH. To demonstrate that chitosan can mediate nanoparticle deposition, we suspended fluorescently labeled latex nanoparticles (100 nm diameter spheres) in a chitosan solution (1%) and performed electrodeposition (0.05 mA/cm2 for several minutes). Results demonstrate that chitosan is required for nanoparticle electrodeposition; chitosan confers spatial selectivity to electrodeposition; and nanoparticles distribute throughout the electrodeposited chitosan film. Additionally, we observed that the deposited films reversibly swell upon rehydration. This work indicates that chitosan provides a simple means to assemble nanoparticles at addressable locations and provides further evidence that stimuli-responsive biological materials may facilitate fabrication at the microscale.

  3. Pressure-mediated reduction of ultrasonically induced cell lysis

    International Nuclear Information System (INIS)

    Ciaravino, V.E.; Miller, M.W.; Carstensen, E.L.

    1981-01-01

    Chinese hamster V-79 cells, exposed in polystyrene tubes for 5 min to 1-MHz continuous-wave ultrasound, were lysed more by a 10 than a 5 W/cm 2 intensity. Higher atmospheric pressure was needed to eliminate lysis with the former relative to the latter intensity, but lysis by 10 W/cm 2 was completely climinated with 2 atm of hydrostatic pressure. The reduction in lysis per unit increase in atmospheric pressure was comparable for both ultrasound intensities

  4. Hypericin-mediated selective photomodification of connective tissues

    Energy Technology Data Exchange (ETDEWEB)

    Hovhannisyan, V., E-mail: hovv@phys.ntu.edu.tw; Guo, H. W.; Chen, Y. F., E-mail: yfchen@phys.ntu.edu.tw [Department of Physics, National Taiwan University, Taipei 106, Taiwan (China); Hovhannisyan, A. [Multimedia and Programming, European Regional Education Academy, Yerevan 0037 (Armenia); Ghukasyan, V. [Neuroscience Center, University of North Carolina at Chapel Hill, North Carolina 27514 (United States); Dong, C. Y., E-mail: cydong@phys.ntu.edu.tw [Department of Physics, National Taiwan University, Taipei 106, Taiwan (China); Center for Quantum Science and Engineering, National Taiwan University, Taipei 106, Taiwan (China)

    2014-12-29

    Controllable modification of biological molecules and supramolecular components of connective tissue are important for biophysical and biomedical applications. Through the use of second harmonic generation imaging, two-photon fluorescence microscopy, and spectrofluorimetry, we found that hypericin, a natural pigment, induces photosensitized destruction of collagen fibers but does not affect elastic fibers and lipids in chicken tendon, skin, and blood vessels. We demonstrated the dynamics and efficiency of collagen photomodification and investigated mechanisms of this processes. Our results suggest that hypericin–mediated photoprocesses in biological tissues may be useful in biomedical applications that require selective modification of connective tissues.

  5. Flow-mediated dilation and exercise blood pressure in healthy adolescents.

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    Lambiase, Maya J; Dorn, Joan; Thurston, Rebecca C; Roemmich, James N

    2014-07-01

    Exercise blood pressure is a robust predictor of cardiovascular disease risk. Endothelial dysfunction occurs early in development of cardiovascular disease and is associated with greater exercise blood pressure in adults. However, it is not yet clear whether endothelial function is associated with exercise blood pressure in youth. The purpose of this study was to examine the relationship between endothelial function, indexed by brachial artery flow-mediated dilation, and submaximal exercise blood pressure in healthy adolescents. Cross-sectional study. Adolescents (N=45) completed a graded submaximal treadmill test. Blood pressure was measured during rest and each exercise stage. Ultrasound measurement of brachial artery flow-mediated dilation was completed on a separate visit. Pearson correlations and multiple regression were used to assess the unadjusted and multivariate adjusted associations between flow-mediated dilation and exercise blood pressure, respectively. Lower flow-mediated dilation was associated with lower diastolic blood pressure (r=0.37, p=0.01) and greater pulse pressure (r=-0.38, p=0.01) during exercise. The significance did not change when adjusting for age, gender, fitness, or resting blood pressure. Exploratory analyses suggest that flow-mediated dilation was associated with exercise diastolic blood pressure primarily among adolescents with low resting diastolic blood pressure. Studies in youth are important to understand the early pathogenesis of cardiovascular disease. Findings from this study suggest that endothelial function may play a role in regulating blood pressure responses during submaximal exercise in healthy adolescents. Copyright © 2013 Sports Medicine Australia. All rights reserved.

  6. Why climate change will invariably alter selection pressures on phenology.

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    Gienapp, Phillip; Reed, Thomas E; Visser, Marcel E

    2014-10-22

    The seasonal timing of lifecycle events is closely linked to individual fitness and hence, maladaptation in phenological traits may impact population dynamics. However, few studies have analysed whether and why climate change will alter selection pressures and hence possibly induce maladaptation in phenology. To fill this gap, we here use a theoretical modelling approach. In our models, the phenologies of consumer and resource are (potentially) environmentally sensitive and depend on two different but correlated environmental variables. Fitness of the consumer depends on the phenological match with the resource. Because we explicitly model the dependence of the phenologies on environmental variables, we can test how differential (heterogeneous) versus equal (homogeneous) rates of change in the environmental variables affect selection on consumer phenology. As expected, under heterogeneous change, phenotypic plasticity is insufficient and thus selection on consumer phenology arises. However, even homogeneous change leads to directional selection on consumer phenology. This is because the consumer reaction norm has historically evolved to be flatter than the resource reaction norm, owing to time lags and imperfect cue reliability. Climate change will therefore lead to increased selection on consumer phenology across a broad range of situations. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  7. Pollinator-mediated selection on nectary depth in Urophysa (Ranunculaceae

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    Li Sun

    2016-04-01

    Full Text Available Pollinator-mediated selection has been considered to be one of major factors that shapes the evolution of flowers by matching flowers to their pollinators on traits associated with attraction of pollinators or mechanical fit. The match between nectary depth, which means the length of the tubular structure formed in many plant species to hide the nectary and store nectar, and the mouthparts length of its major nectar-foraging pollinators has been repeatedly demonstrated as an example, because this trait have shown a positive relationship with pollen removal and deposition in experimental manipulations in many synpetalous plants and orchid family. However, it remains unclear how pollinator-mediated selection affects the evolution of nectary depth in choripetalous and actinomorphic flowers, such as most flowers in Ranunculaceae. Here we investigated floral characteristics and pollinators in Urophysa rockii Ulbr. and U. henryi (Oliv. Ulbr., as they are quite the same in habitat, anthesis and morphological characteristics except for nectary depth. Both of these species have flat white sepals and yellow petals each has a spatial structure at the base that contains nectar, but the nectary depth of U. rockii is deeper than that of U. henryi, for the former petals are shortly spurred about 3-4mm in length while the latter are saccate. Meanwhile, the flowers of both species are most frequently visited by Apis cerana, the Chinese honey bee, and one or two species of hover fly, Syrphidae, but only A. cerana was able to forage nectar in U. rockii while all visitors can forage nectar in U. henryi. A. cerana always lands on the center of a flower and projects its proboscis into each petal when its thorax touches anthers and stigmas. The difference between two species is that U. rockii was visited by A. cerana with a higher frequency, longer visiting time per flower and more activities on flowers than U. henryi. Besides, the petal width and its nectary depth of

  8. Selective hydrogen purification through graphdiyne under ambient temperature and pressure

    Science.gov (United States)

    Cranford, Steven W.; Buehler, Markus J.

    2012-07-01

    Graphdiyne, a recently synthesized one-atom-thick carbon allotrope, is atomistically porous - characterized by a regular ``nanomesh'' - and suggests application as a separation membrane for hydrogen purification. Here we report a full atomistic reactive molecular dynamics investigation to determine the selective diffusion properties of hydrogen (H2) amongst carbon monoxide (CO) and methane (CH4), a mixture otherwise known as syngas, a product of the gasification of renewable biomass (such as animal wastes). Under constant temperature simulations, we find the mass flux of hydrogen molecules through a graphdiyne membrane to be on the order of 7 to 10 g cm-2 s-1 (between 300 K and 500 K), with carbon monoxide and methane remaining isolated. Using a simple Arrhenius relation, we determine the energy required for permeation on the order of 0.11 +/- 0.03 eV for single H2 molecules. We find that addition of marginal applied force (approximately 1 to 2 pN per molecule, representing a controlled pressure gradient, ΔP, on the order of 100 to 500 kPa) can successfully enhance the separation of hydrogen gas. Addition of larger driving forces (50 to 100 pN per molecule) is required to selectively filter carbon monoxide or methane, suggesting that, under near-atmospheric conditions, only hydrogen gas will pass such a membrane. Graphdiyne provides a unique, chemically inert and mechanically stable platform facilitating selective gas separation at nominal pressures using a homogeneous material system, without a need for chemical functionalization or the explicit introduction of molecular pores.

  9. Kidney Dysfunction Mediates Salt-Induced Increases in Blood Pressure

    Science.gov (United States)

    Hall, John E.

    2016-01-01

    Chronic excess salt intake increases the risk for hypertension and moderation of salt intake is an important strategy for prevention of cardiovascular and kidney disease, especially in salt-sensitive subjects. Although short-term blood pressure (BP) responses to high salt intake over several days are highly variable, chronic high salt intake worsens BP salt-sensitivity. Aging, diabetes, hypertension, and various acquired and genetic kidney disorders also exacerbate salt-sensitivity of BP. Kidney dysfunction, characterized by impaired pressure natriuresis, has been demonstrated in all forms of experimental and human genetic or acquired salt-sensitive hypertension studied thus far. Abnormalities of kidney function that directly or indirectly increase NaCl reabsorption, decrease glomerular capillary filtration coefficient, or cause nephron injury/loss exacerbate BP salt-sensitivity. In most cases, salt-sensitive hypertension is effectively treated with drugs that increase glomerular filtration rate or reduce renal NaCl reabsorption (e.g. diuretics, renin-angiotensin-aldosterone system blockers). Increased vascular resistance may occur concomitantly or secondarily to kidney dysfunction and increased BP in salt-sensitive hypertension. However, primary increases in non-renal vascular resistance have not been shown to cause salt-sensitive hypertension or long-term changes in BP in the absence of impaired renal-pressure natriuresis. The mechanisms responsible for increased total peripheral resistance (TPR) during high salt intake in salt-sensitive subjects are not fully understood but likely involve pressure-dependent and/or flow-dependent autoregulation in peripheral tissues as well as neurohormonal factors that occur concomitantly with kidney dysfunction. Physiological studies have demonstrated that increased BP almost invariably initiates secondary pressure-dependent functional and structural vascular changes that increase TPR. PMID:26927007

  10. Extensive Admixture and Selective Pressure Across the Sahel Belt.

    Science.gov (United States)

    Triska, Petr; Soares, Pedro; Patin, Etienne; Fernandes, Veronica; Cerny, Viktor; Pereira, Luisa

    2015-11-26

    Genome-wide studies of African populations have the potential to reveal powerful insights into the evolution of our species, as these diverse populations have been exposed to intense selective pressures imposed by infectious diseases, diet, and environmental factors. Within Africa, the Sahel Belt extensively overlaps the geographical center of several endemic infections such as malaria, trypanosomiasis, meningitis, and hemorrhagic fevers. We screened 2.5 million single nucleotide polymorphisms in 161 individuals from 13 Sahelian populations, which together with published data cover Western, Central, and Eastern Sahel, and include both nomadic and sedentary groups. We confirmed the role of this Belt as a main corridor for human migrations across the continent. Strong admixture was observed in both Central and Eastern Sahelian populations, with North Africans and Near Eastern/Arabians, respectively, but it was inexistent in Western Sahelian populations. Genome-wide local ancestry inference in admixed Sahelian populations revealed several candidate regions that were significantly enriched for non-autochthonous haplotypes, and many showed to be under positive selection. The DARC gene region in Arabs and Nubians was enriched for African ancestry, whereas the RAB3GAP1/LCT/MCM6 region in Oromo, the TAS2R gene family in Fulani, and the ALMS1/NAT8 in Turkana and Samburu were enriched for non-African ancestry. Signals of positive selection varied in terms of geographic amplitude. Some genomic regions were selected across the Belt, the most striking example being the malaria-related DARC gene. Others were Western-specific (oxytocin, calcium, and heart pathways), Eastern-specific (lipid pathways), or even population-restricted (TAS2R genes in Fulani, which may reflect sexual selection). © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  11. Radiation-pressure-mediated control of an optomechanical cavity

    Science.gov (United States)

    Cripe, Jonathan; Aggarwal, Nancy; Singh, Robinjeet; Lanza, Robert; Libson, Adam; Yap, Min Jet; Cole, Garrett D.; McClelland, David E.; Mavalvala, Nergis; Corbitt, Thomas

    2018-01-01

    We describe and demonstrate a method to control a detuned movable-mirror Fabry-Pérot cavity using radiation pressure in the presence of a strong optical spring. At frequencies below the optical spring resonance, self-locking of the cavity is achieved intrinsically by the optomechanical (OM) interaction between the cavity field and the movable end mirror. The OM interaction results in a high rigidity and reduced susceptibility of the mirror to external forces. However, due to a finite delay time in the cavity, this enhanced rigidity is accompanied by an antidamping force, which destabilizes the cavity. The cavity is stabilized by applying external feedback in a frequency band around the optical spring resonance. The error signal is sensed in the amplitude quadrature of the transmitted beam with a photodetector. An amplitude modulator in the input path to the cavity modulates the light intensity to provide the stabilizing radiation pressure force.

  12. Detecting non-coding selective pressure in coding regions

    Directory of Open Access Journals (Sweden)

    Blanchette Mathieu

    2007-02-01

    Full Text Available Abstract Background Comparative genomics approaches, where orthologous DNA regions are compared and inter-species conserved regions are identified, have proven extremely powerful for identifying non-coding regulatory regions located in intergenic or intronic regions. However, non-coding functional elements can also be located within coding region, as is common for exonic splicing enhancers, some transcription factor binding sites, and RNA secondary structure elements affecting mRNA stability, localization, or translation. Since these functional elements are located in regions that are themselves highly conserved because they are coding for a protein, they generally escaped detection by comparative genomics approaches. Results We introduce a comparative genomics approach for detecting non-coding functional elements located within coding regions. Codon evolution is modeled as a mixture of codon substitution models, where each component of the mixture describes the evolution of codons under a specific type of coding selective pressure. We show how to compute the posterior distribution of the entropy and parsimony scores under this null model of codon evolution. The method is applied to a set of growth hormone 1 orthologous mRNA sequences and a known exonic splicing elements is detected. The analysis of a set of CORTBP2 orthologous genes reveals a region of several hundred base pairs under strong non-coding selective pressure whose function remains unknown. Conclusion Non-coding functional elements, in particular those involved in post-transcriptional regulation, are likely to be much more prevalent than is currently known. With the numerous genome sequencing projects underway, comparative genomics approaches like that proposed here are likely to become increasingly powerful at detecting such elements.

  13. Photodynamic Priming Mitigates Chemotherapeutic Selection Pressures and Improves Drug Delivery.

    Science.gov (United States)

    Huang, Huang-Chiao; Rizvi, Imran; Liu, Joyce; Anbil, Sriram; Kalra, Ashish; Lee, Helen; Baglo, Yan; Paz, Nancy; Hayden, Douglas; Pereira, Steve; Pogue, Brian W; Fitzgerald, Jonathan; Hasan, Tayyaba

    2018-01-15

    Physiologic barriers to drug delivery and selection for drug resistance limit survival outcomes in cancer patients. In this study, we present preclinical evidence that a subtumoricidal photodynamic priming (PDP) strategy can relieve drug delivery barriers in the tumor microenvironment to safely widen the therapeutic window of a nanoformulated cytotoxic drug. In orthotopic xenograft models of pancreatic cancer, combining PDP with nanoliposomal irinotecan (nal-IRI) prevented tumor relapse, reduced metastasis, and increased both progression-free survival and 1-year disease-free survival. PDP enabled these durable improvements by targeting multiple tumor compartments to (i) increase intratumoral drug accumulation by >10-fold, (ii) increase the duration of drug exposure above a critical therapeutic threshold, and (iii) attenuate surges in CD44 and CXCR4 expression, which mediate chemoresistance often observed after multicycle chemotherapy. Overall, our results offer preclinical proof of concept for the effectiveness of PDP to minimize risks of tumor relapse, progression, and drug resistance and to extend patient survival. Significance: A biophysical priming approach overcomes key treatment barriers, significantly reduces metastases, and prolongs survival in orthotopic models of human pancreatic cancer. Cancer Res; 78(2); 558-71. ©2017 AACR . ©2017 American Association for Cancer Research.

  14. Circadian clock-mediated regulation of blood pressure.

    Science.gov (United States)

    Douma, Lauren G; Gumz, Michelle L

    2017-12-02

    Most bodily functions vary over the course of a 24h day. Circadian rhythms in body temperature, sleep-wake cycles, metabolism, and blood pressure (BP) are just a few examples. These circadian rhythms are controlled by the central clock in the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks located throughout the body. Light and food cues entrain these clocks to the time of day and this synchronicity contributes to the regulation of a variety of physiological processes with effects on overall health. The kidney, brain, nervous system, vasculature, and heart have been identified through the use of mouse models and clinical trials as peripheral clock regulators of BP. The dysregulation of this circadian pattern of BP, with or without hypertension, is associated with increased risk for cardiovascular disease. The mechanism of this dysregulation is unknown and is a growing area of research. In this review, we highlight research of human and mouse circadian models that has provided insight into the roles of these molecular clocks and their effects on physiological functions. Additional tissue-specific studies of the molecular clock mechanism are needed, as well as clinical studies including more diverse populations (different races, female patients, etc.), which will be critical to fully understand the mechanism of circadian regulation of BP. Understanding how these molecular clocks regulate the circadian rhythm of BP is critical in the treatment of circadian BP dysregulation and hypertension. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Floral symmetry: pollinator-mediated stabilizing selection on flower size in bilateral species.

    Science.gov (United States)

    Gong, Yan-Bing; Huang, Shuang-Quan

    2009-11-22

    Pollinator-mediated stabilizing selection (PMSS) has been proposed as the driver of the evolutionary shift from radial to bilateral symmetry of flowers. Studies have shown that variation in flower size is lower in bilateral than in radial species, but whether bilateral flowers experience more stabilizing selection pressures by employing fewer, more specialized pollinators than radial flowers remains unclear. To test the PMSS hypothesis, we investigate plant-pollinator interactions from a whole community in an alpine meadow in Hengduan Mountains, China, to examine: (i) variance in flower size and level of ecological generalization (pollinator diversity calculated using functional groups) in 14 bilateral and 13 radial species and (ii) the role pollinator diversity played in explaining the difference of variance in flower size between bilateral and radial species. Our data showed that bilateral species had less variance in flower size and were visited by fewer pollinator groups. Pollinator diversity accounted for up to 40 per cent of the difference in variance in flower size between bilateral and radial species. The mediator effect of pollinator diversity on the relationship between floral symmetry and variance in flower size in the community is consistent with the PMSS hypothesis.

  16. Selected reading on introduction to pressure tube technology

    International Nuclear Information System (INIS)

    Causey, A.R.; Coleman, C.E.; Ells, C.E.

    1981-10-01

    Four lectures on pressure tube technology were presented at Sheridan Park, Ontario, on 1981 June 1. The titles were 'Pressure Tubes and Their Operational Environment', 'Fabrication, Inspection and Properties of Current Production Pressure Tubes', 'In-Reactor Deformation of Fuel Channels', and 'Potential Failure Modes in Pressure Tubes'. This report lists the references used in preparing the lectures. It is intended to provide a starting point in reading for people who need to become familiar with pressure tube technology but have little prior knowledge of the topic

  17. Peer pressure and alcohol use in young men: a mediation analysis of drinking motives.

    Science.gov (United States)

    Studer, Joseph; Baggio, Stéphanie; Deline, Stéphane; N'Goran, Alexandra A; Henchoz, Yves; Mohler-Kuo, Meichun; Daeppen, Jean-Bernard; Gmel, Gerhard

    2014-07-01

    Peer pressure (PP) has been shown to play a major role in the development and continuation of alcohol use and misuse. To date, almost all the studies investigating the association of PP with alcohol use only considered the PP for misconduct but largely ignored other aspects of PP, such as pressure for peer involvement and peer conformity. Moreover, it is not clear whether the association of PP with alcohol use is direct or mediated by other factors. The aim of the present study was to investigate the association of different aspects of peer pressure (PP) with drinking volume (DV) and risky single-occasion drinking (RSOD), and to explore whether these associations were mediated by drinking motives (DM). A representative sample of 5521 young Swiss men, aged around 20 years old, completed a questionnaire assessing their usual weekly DV, the frequency of RSOD, DM (i.e. enhancement, social, coping, and conformity motives), and 3 aspects of PP (i.e. misconduct, peer involvement, and peer conformity). Associations between PP and alcohol outcomes (DV and RSOD) as well as the mediation of DM were tested using structural equation models. Peer pressure to misconduct was associated with more alcohol use, whereas peer involvement and peer conformity were associated with less alcohol use. Associations of drinking outcomes with PP to misconduct and peer involvement were partially mediated by enhancement and coping motives, while the association with peer conformity was partially mediated by enhancement and conformity motives. Results suggest that PP to misconduct constitutes a risk factor, while peer conformity and peer involvement reflect protective factors with regard to alcohol use. Moreover, results from the mediation analyses suggest that part of the association of PP with alcohol use came indirectly through DM: PP was associated with DM, which in turn were associated with alcohol use. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Oxybiotest project: microorganisms under pressure. Hyperbaric oxygen (HBO and simple pressure interaction on selected bacteria

    Directory of Open Access Journals (Sweden)

    Zanon Vincenzo

    2012-09-01

    Full Text Available Abstract Background HyperBaric Oxygen (HBO therapy involves exposure to pure oxygen in a pressurized room, and it is an already well-established treatment for various conditions, including those originated by serious infections. Starting from the observation of an increased number of patients who were accessing our HBO units for diseases supported from concomitant multidrug-resistant microorganisms, as well as considering the evident clinical benefit and laboratory final outcome of those patients at the end of the treatment, aim of our study was to measure, or better define at least, if there was any interaction between a hyperbaric environment and some selected microorganisms and if those positive results were due to the increased oxygen partial pressure (pO2 value or just to the increased pressure, regardless of the fraction of inspired oxygen (FiO2 applied (21÷100%. Design and methods We applied various increased pO2 values in a hyperbaric environment. Our study design was tailored in four steps to answer four specific questions, ordered in a progressive process: OxyBioTest (OBT-1,2,3, and 4. Specifically, we chose to investigate possible changes in the Minimum Inhibitory Concentration (MIC and in the Minimum Bactericidal Concentration (MBC of multi-resistant microorganisms after a single session of hyperbaric therapy. Results OBT-1 and OBT-2 provide a semi-quantitative confirmation of the bacterio-cidal and cytostatic effects of HBO. HBO is cidal only if the total exposure pressure is elevated, and cidal or cytostatic effect are not always dependent on the pO2 applied. OBT-4 has shown the adjuvant effect of HBO and antimicrobial drug against some selected bacteria. Discussion We seem allowed to hypothesize that only in case of a good approach to a lesion, permitting smaller bacterial loads thanks to surgical debridement and/or eventual antibiotic therapy for example, You can observe the clear effectiveness of the HyperBaric Oxygen (HBO

  19. Interface pressure mapping pilot study to select surfaces that effectively redistribute pediatric occipital pressure.

    Science.gov (United States)

    Higer, Samantha; James, Thomas

    2016-02-01

    The aim of this pilot study was to better inform clinical decisions to prevent pediatric occipital pressure ulcers with quantitative data to choose an appropriate reactive support surface. A commercially available capacitive pressure mapping system (XSENSOR, X3 Medical Seat System, Calgary, Canada) was used to evaluate a standard pediatric mattress and four commercially available pressure-redistributing support surfaces. The pressure mapping system was validated for use in the pediatric population through studies on sensitivity, accuracy, creep, and repeatability. Then, a pilot pressure mapping study on healthy children under 6 years old (n = 22) was performed to determine interface pressure and pressure distribution between the occipital region of the skull and each surface: standard mattress, gel, foam, air and fluidized. The sensor was adequate to measure pressure generated by pediatric occipital loading, with 0.5-9% error in accuracy in the 25-95 mmHg range. The air surface had the lowest mean interface pressure (p pressure index (PPI), defined as the peak pressure averaged over four sensels, (p pressure for mattress, foam, fluidized, gel, and air materials were 24.8 ± 4.42, 24.1 ± 1.89, 19.4 ± 3.25, 17.9 ± 3.10, and 14.2 ± 1.41 mmHg, respectively. The air surface also had the most homogenous pressure distribution, with the highest mean to PPI ratio (p surfaces (p surface was the most effective pressure-redistributing material for pediatric occipital pressure as it had the lowest interface pressure and a homogeneous pressure distribution. This implies effective envelopment of the bony prominence of the occiput and increasing contact area to decrease peak pressure points. Copyright © 2015 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

  20. Load on Buried Pressure Conduits with Reference to Selection of ...

    African Journals Online (AJOL)

    The use of asbestos-cement pressure conduits is becoming popular even in developing countries. Asbestos-cement pipe can withstand internal pressure of up to 1.4 MPa and is unaffected by corrosion. Its other virtues are that it is light in weight, could be easily cut and filed, is not easily fractured if properly cradled, and can ...

  1. Pressure-assisted selective preconcentration in a straight nanochannel.

    Science.gov (United States)

    Louër, Anne-Claire; Plecis, Adrien; Pallandre, Antoine; Galas, Jean-Christophe; Estevez-Torres, André; Haghiri-Gosnet, Anne-Marie

    2013-08-20

    We investigate the preconcentration profiles of a fluorescein and bovine serum albumin derivatized with this fluorescent tag in a microfluidic chip bearing a nanoslit. A new preconcentration method in which a hydrodynamic pressure is added to both electroosmotic and electrophoretic contributions is proposed to monitor the location of the preconcentration frontline. A simple predictive model of this pressure-assisted electropreconcentration is proposed for the evolution of the flow profile along this micro/nano/microfluidic structure. We show with a small analyte such as fluorescein that the additional hydrostatic pressure mode enables to stabilize the concentration polarization (CP) effect, resulting in better control of the cathodic focusing (CF) peak. For BSA (bovine serum albumin), we exhibit that the variation of the hydrodynamic pressure can have an even more drastic effect on the preconcentration. We show that, depending on this hydrodynamic pressure, the preconcentration can be chosen, either in the cathodic side or in the anodic one. For the first time, we prove here that both anodic focusing (AF) and cathodic focusing (CF) regimes can be reached in the same structures. These results also open new routes for the detection and the quantification of low abundance biomarkers.

  2. Pulse Arrival Time as surrogate for systolic blood pressure changes during impending neurally mediated syncope.

    Science.gov (United States)

    Muehlsteff, Jens; Ritz, Anita; Drexel, Thomas; Eickholt, Christian; Carvalho, Paulo; Couceiro, Ricardo; Kelm, Malte; Meyer, Christian

    2012-01-01

    Blood pressure regulation failures cause neurally mediated syncope often resulting in a fall. A warning device might help to make patients aware of an impending critical event or even trigger the patient to perform countermeasures such as lying down or isometric exercises. We previously demonstrated that the Pulse Arrival Time (PAT) methodology is a potential approach to enable early detection of impending faints. The aim of the present study was to evaluate whether PAT can be used as an easy to measure beat-to-beat surrogate for systolic blood pressure (SBP) changes during a passive standing exercise (head-up tilt table testing (HUTT)). A significant PAT increase of more than 10 % was accompanied with a critical SBP decrease in syncope patients. Although PAT is in general not considered as a good measure of absolute blood pressure we found strong correlations (R>0.89, P<0.01) of SBP and PAT after PAT began to increase. Therefore, our data suggest that the pulse arrival time is useful to monitor blood pressure changes in patients with neurally mediated syncope. This might open up new avenues to prevent falls in these patients.

  3. Vapor pressures and thermophysical properties of selected monoterpenoids

    Czech Academy of Sciences Publication Activity Database

    Štejfa, V.; Dergal, F.; Mokbel, I.; Fulem, Michal; Jose, J.; Růžička, K.

    Roč. 406 , Nov (2015), 124-133 ISSN 0378-3812 Institutional support: RVO:68378271 Keywords : monoterpenoids * vapor pressure * heat capacity * ideal-gas thermodynamic properties * vaporization and sublimation enthalpy Subject RIV: BJ - Thermodynamics Impact factor: 1.846, year: 2015

  4. Vapor Pressure of Selected Aliphatic Alcohols by Ebulliometry. Part 1

    Czech Academy of Sciences Publication Activity Database

    Čenský, M.; Roháč, V.; Růžička, K.; Fulem, M.; Aim, Karel

    2010-01-01

    Roč. 298, č. 2 (2010), s. 192-198 ISSN 0378-3812 R&D Projects: GA AV ČR IAA400720710 Institutional research plan: CEZ:AV0Z40720504 Keywords : vapor pressure * ebulliometry * aliphatic alcohols Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.253, year: 2010

  5. Peierls distortion mediated reversible phase transition in GeTe under pressure.

    Science.gov (United States)

    Sun, Zhimei; Zhou, Jian; Mao, Ho-Kwang; Ahuja, Rajeev

    2012-04-17

    With the advent of big synchrotron facilities around the world, pressure is now routinely placed to design a new material or manipulate the properties of materials. In GeTe, an important phase-change material that utilizes the property contrast between the crystalline and amorphous states for data storage, we observed a reversible phase transition of rhombohedral ↔ rocksalt ↔ orthorhombic ↔ monoclinic coupled with a semiconductor ↔ metal interconversion under pressure on the basis of ab initio molecular dynamics simulations. This interesting reversible phase transition under pressure is believed to be mediated by Peierls distortion in GeTe. Our results suggest a unique way to understand the reversible phase transition and hence the resistance switching that is crucial to the applications of phase-change materials in nonvolatile memory. The present finding can also be expanded to other IV-VI semiconductors.

  6. Highly selective defect-mediated photochemical CO2 conversion over fluorite ceria under ambient conditions.

    Science.gov (United States)

    Jiang, Dong; Wang, Wenzhong; Gao, Erping; Sun, Songmei; Zhang, Ling

    2014-02-25

    A highly selective defect-mediated photochemical CO2 conversion to CO over defective CeO2 nanorods under ambient conditions (CO2 400 ppm) is presented. The local strain and surface oxygen vacancies embedded in the defect-rich CeO2 are suggested to play a decisive role in mediating the photochemical CO2 conversion.

  7. Pathogen-mediated selection for MHC variability in wild zebrafish

    Czech Academy of Sciences Publication Activity Database

    Smith, C.; Ondračková, Markéta; Spence, R.; Adams, S.; Betts, D. S.; Mallon, E.

    2011-01-01

    Roč. 13, č. 6 (2011), s. 589-605 ISSN 1522-0613 Institutional support: RVO:68081766 Keywords : digenean * frequency-dependent selection * heterozygote advantage * major histocompatibility complex * metazoan parasite * pathogen-driven selection Subject RIV: EG - Zoology Impact factor: 1.029, year: 2011

  8. Biolistic mediated sorghum (Sorghum bicolor L. Moench) transformation via mannose and bialaphos based selection systems

    CSIR Research Space (South Africa)

    Grootboom, AW

    2010-01-01

    Full Text Available studied the utility of bialaphos and phosphomannose isomerase selectable markers in microprojectile mediated transformation of P898012, a sorghum inbred line generally considered amenable to in vitro manipulation. Two plasmids containing bar gene, encoding...

  9. Predator-mediated natural selection on the wings of the damselfly Calopteryx splendens: differences in selection among trait types.

    Science.gov (United States)

    Kuchta, Shawn R; Svensson, Erik I

    2014-07-01

    Traits that increase mating success in males may come at a cost, such as an increased risk of predation. However, predator-mediated selection is challenging to document in natural populations, hampering our understanding of the trade-offs between sexual selection and predation. Here we report on a study of predator-mediated natural selection on wing traits in the damselfly Calopteryx splendens, the males of which possess conspicuous wing patches. Wagtails (genus Motacilla) are important avian predators of C. splendens, capturing them in flight and removing the wings prior to consumption. Using geometric morphometric techniques, we quantified the strength and mode of selection on wing traits by comparing wings from depredated individuals with the standing variation present in the population. Our results reveal that predator-mediated selection is stronger on secondary sexual characters than on size and shape, suggesting that traits related to flight performance are closer to their adaptive peaks. This could be a consequence of the long-term evolutionary association with avian predators, whereas stronger selection on conspicuous secondary sexual traits may reflect trade-offs between sexual and natural selection. Finally, even though C. splendens possesses nearly identical fore- and hindwings, we found evidence for divergent selection between them.

  10. Vapor pressures and thermophysical properties of selected hexenols and recommended vapor pressure for hexan-1-ol

    Czech Academy of Sciences Publication Activity Database

    Štejfa, V.; Fulem, Michal; Růžička, K.; Matějka, P.

    2015-01-01

    Roč. 402, Sep (2015), 18-29 ISSN 0378-3812 Institutional support: RVO:68378271 Keywords : alcohols * vapor pressure * heat capacity * ideal - gas thermodynamic properties * vaporization enthalpy Subject RIV: BJ - Thermodynamics Impact factor: 1.846, year: 2015

  11. Effect of stocking pressure on selected diet quality, intake and ...

    African Journals Online (AJOL)

    ABUBAKER

    Keywords: Cocksfoot, diet selection, pasture availability, perennial rye grass, performance. # Corresponding author. Email: willem.vanniekerk@up.ac.za. Introduction. Animal productivity and efficiency of production are functions of the level of nutrition, which in turn is dependent on the animal's requirements, nutrient content ...

  12. Analysis of polymorphisms and selective pressures on ama1 gene ...

    Indian Academy of Sciences (India)

    Chuen Yang Chua

    2017-09-05

    Sep 5, 2017 ... The presence of purifying selection and low nucleotide diversity indicated that domain II of Pkama1 can be used as a target for vaccine development. .... lected from hospitals of Kudat, Keningau and Queen. Elizabeth in 2012, after a written consent for sample collection was obtained. This study was ...

  13. CpG islands undermethylation in human genomic regions under selective pressure.

    Directory of Open Access Journals (Sweden)

    Sergio Cocozza

    Full Text Available DNA methylation at CpG islands (CGIs is one of the most intensively studied epigenetic mechanisms. It is fundamental for cellular differentiation and control of transcriptional potential. DNA methylation is involved also in several processes that are central to evolutionary biology, including phenotypic plasticity and evolvability. In this study, we explored the relationship between CpG islands methylation and signatures of selective pressure in Homo Sapiens, using a computational biology approach. By analyzing methylation data of 25 cell lines from the Encyclopedia of DNA Elements (ENCODE Consortium, we compared the DNA methylation of CpG islands in genomic regions under selective pressure with the methylation of CpG islands in the remaining part of the genome. To define genomic regions under selective pressure, we used three different methods, each oriented to provide distinct information about selective events. Independently of the method and of the cell type used, we found evidences of undermethylation of CGIs in human genomic regions under selective pressure. Additionally, by analyzing SNP frequency in CpG islands, we demonstrated that CpG islands in regions under selective pressure show lower genetic variation. Our findings suggest that the CpG islands in regions under selective pressure seem to be somehow more "protected" from methylation when compared with other regions of the genome.

  14. Extensive Admixture and Selective Pressure Across the Sahel Belt

    Czech Academy of Sciences Publication Activity Database

    Triska, P.; Soares, P.; Patin, E.; Fernandes, V.; Černý, Viktor; Pereira, L.

    2015-01-01

    Roč. 7, č. 12 (2015), s. 3484-3495 ISSN 1759-6653 R&D Projects: GA ČR GA13-37998S Institutional support: RVO:67985912 Keywords : genome-wide diversity * admixture * selection * Sahel Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 4.098, year: 2015 http://gbe.oxfordjournals.org/content/7/12/3484.full.pdf+html

  15. Differential Selective Pressures Experienced by the Aurora Kinase Gene Family

    Directory of Open Access Journals (Sweden)

    Joni M. Seeling

    2017-12-01

    Full Text Available Aurora kinases (AKs are serine/threonine kinases that are essential for cell division. Humans have three AK genes: AKA, AKB, and AKC. AKA is required for centrosome assembly, centrosome separation, and bipolar spindle assembly, and its mutation leads to abnormal spindle morphology. AKB is required for the spindle checkpoint and proper cytokinesis, and mutations cause chromosome misalignment and cytokinesis failure. AKC is expressed in germ cells, and has a role in meiosis analogous to that of AKB in mitosis. Mutation of any of the three isoforms can lead to cancer. AK proteins possess divergent N- and C-termini and a conserved central catalytic domain. We examined the evolution of the AK gene family using an identity matrix and by building a phylogenetic tree. The data suggest that AKA is the vertebrate ancestral gene, and that AKB and AKC resulted from gene duplication in placental mammals. In a nonsynonymous/synonymous rate substitution analysis, we found that AKB experienced the strongest, and AKC the weakest, purifying selection. Both the N- and C-termini and regions within the kinase domain experienced differential selection among the AK isoforms. These differentially selected sequences may be important for species specificity and isoform specificity, and are therefore potential therapeutic targets.

  16. Tetracycline resistance genes persist in soil amended with cattle feces independently from chlortetracycline selection pressure

    NARCIS (Netherlands)

    Kyselkova, Martina; Kotrbova, Lucie; Bhumibhamon, Gamonsiri; Chronakova, Alica; Jirout, Jiri; Vrchotova, Nadezda; Schmitt, Heike; Elhottova, Dana

    Antibiotic residues and antibiotic resistance genes originating from animal waste represent environmental pollutants with possible human health consequences. In this study, we addressed the question whether chlortetracycline (CTC) residues in soils can act as selective pressure enhancing the

  17. Selection Demands and Working Memory Mediate Interference during Naming

    OpenAIRE

    Julie W Hughes

    2015-01-01

    Naming pictures in semantically related (DOG, CAT, PIG) vs. unrelated groups (DOG, BUS, EAR) across numerous cycles (blocked-cyclic naming; BCN) results in increasingly slower response times (RTs) (e.g., Belke, 2008). This semantic interference (SI) is thought to arise because selecting responses is more demanding in the context of similar vs. dissimilar items (e.g., Schnur, Schwartz, Brecher, & Hodgson, 2006). We may attenuate SI depending on our capacity to reduce interference from competit...

  18. Iodine-Mediated Neutral and Selective N-Boc Deprotection

    OpenAIRE

    Pavan Kumar, G.; Rambabu, D.; Basaveswara Rao, M. V.; Pal, Manojit

    2013-01-01

    A simple, efficient, and alternative method has been developed for the N-Boc deprotection of structurally diverse protected amines. Selective removal of N-Boc groups was achieved with excellent yields under a solvent-free condition or in a solvent using iodine as a catalyst. The methodology involving the first use of iodine for N-Boc deprotection of protected amines represents an effective and useful alternative to the previously reported methods.

  19. Perceptions of parental pressure to eat and eating behaviours in preadolescents: the mediating role of anxiety.

    Science.gov (United States)

    Houldcroft, Laura; Farrow, Claire; Haycraft, Emma

    2014-09-01

    Previous research suggests that parental controlling feeding practices are associated with children's overeating and undereating behaviours. However, there is limited research addressing the link between children's mental health symptoms (specifically anxiety and depression) and their reports of eating behaviours, despite knowledge that these psychopathologies often co-exist. The current study aimed to identify the relationships between preadolescents' perceptions of their parents' feeding practices with reports of their own anxiety, depression and eating behaviours. Three hundred and fifty-six children (mean age 8.75 years) completed questionnaires measuring their dietary restraint, emotional eating and external eating, as well as their perceptions of their parents' use of pressure to eat and restriction of food. Children also completed measures of general anxiety, social anxiety and depression symptomology. Results indicated that preadolescents' eating behaviours were associated with their perceptions of the controlling feeding practices their parents used with them. Preadolescents' dietary restraint, emotional eating and external eating behaviours were positively associated with their reports of general and social anxiety, and depression symptomology. In addition, perceptions of parental pressure to eat were positively related to preadolescents' anxiety and depression levels. Child anxiety (general and social) was found to mediate the relationship between perceptions of parental pressure to eat and preadolescents' eating behaviours (dietary restraint, emotional eating and external eating). The results suggest that greater anxiety in preadolescents may explain why children who perceive greater pressure to eat by their parents are more likely to exhibit maladaptive eating behaviours. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Unlocking High-Salinity Desalination with Cascading Osmotically Mediated Reverse Osmosis: Energy and Operating Pressure Analysis.

    Science.gov (United States)

    Chen, Xi; Yip, Ngai Yin

    2018-02-20

    Current practice of using thermally driven methods to treat hypersaline brines is highly energy-intensive and costly. While conventional reverse osmosis (RO) is the most efficient desalination technique, it is confined to purifying seawater and lower salinity sources. Hydraulic pressure restrictions and elevated energy demand render RO unsuitable for high-salinity streams. Here, we propose an innovative cascading osmotically mediated reverse osmosis (COMRO) technology to overcome the limitations of conventional RO. The innovation utilizes the novel design of bilateral countercurrent reverse osmosis stages to depress the hydraulic pressure needed by lessening the osmotic pressure difference across the membrane, and simultaneously achieve energy savings. Instead of the 137 bar required by conventional RO to desalinate 70 000 ppm TDS hypersaline feed, the highest operating pressure in COMRO is only 68.3 bar (-50%). Furthermore, up to ≈17% energy saving is attained by COMRO (3.16 kWh/m 3 , compared to 3.79 kWh/m 3 with conventional RO). When COMRO is employed to boost the recovery of seawater desalination to 70% from the typical 35-50%, energy savings of up to ≈33% is achieved (2.11 kWh/m 3 , compared to 3.16 kWh/m 3 with conventional RO). Again, COMRO can operate at a moderate hydraulic pressure of 80 bar (25% lower than 113 bar of conventional RO). This study highlights the encouraging potential of energy-efficient COMRO to access unprecedented high recovery rates and treat hypersaline brines at moderate hydraulic pressures, thus extending the capabilities of membrane-based technologies for high-salinity desalination.

  1. The mathematics of random mutation and natural selection for multiple simultaneous selection pressures and the evolution of antimicrobial drug resistance.

    Science.gov (United States)

    Kleinman, Alan

    2016-12-20

    The random mutation and natural selection phenomenon act in a mathematically predictable behavior, which when understood leads to approaches to reduce and prevent the failure of the use of these selection pressures when treating infections and cancers. The underlying principle to impair the random mutation and natural selection phenomenon is to use combination therapy, which forces the population to evolve to multiple selection pressures simultaneously that invoke the multiplication rule of probabilities simultaneously as well. Recently, it has been seen that combination therapy for the treatment of malaria has failed to prevent the emergence of drug-resistant variants. Using this empirical example and the principles of probability theory, the derivation of the equations describing this treatment failure is carried out. These equations give guidance as to how to use combination therapy for the treatment of cancers and infectious diseases and prevent the emergence of drug resistance. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Pressure-induced vascular oxidative stress is mediated through activation of integrin-linked kinase 1/betaPIX/Rac-1 pathway.

    Science.gov (United States)

    Vecchione, Carmine; Carnevale, Daniela; Di Pardo, Alba; Gentile, Maria Teresa; Damato, Antonio; Cocozza, Germana; Antenucci, Giovanna; Mascio, Giada; Bettarini, Umberto; Landolfi, Alessandro; Iorio, Luca; Maffei, Angelo; Lembo, Giuseppe

    2009-11-01

    High blood pressure induces a mechanical stress on vascular walls and evokes oxidative stress and vascular dysfunction. The aim of this study was to characterize the intracellular signaling causing vascular oxidative stress in response to pressure. In carotid arteries subjected to high pressure levels, we observed not only an impaired vasorelaxation, increased superoxide production, and NADPH oxidase activity, but also a concomitant activation of Rac-1, a small G protein. Selective inhibition of Rac-1, with an adenovirus carrying a dominant-negative Rac-1 mutant, significantly reduced NADPH oxidase activity and oxidative stress and, more importantly, rescued vascular function in carotid arteries at high pressure. The analysis of molecular events associated with mechanotransduction demonstrated at high pressure levels an overexpression of integrin-linked kinase 1 and its recruitment to plasma membrane interacting with paxillin. The inhibition of integrin-linked kinase 1 by small interfering RNA impaired Rac-1 activation and rescued oxidative stress-induced vascular dysfunction in response to high pressure. Finally, we showed that betaPIX, a guanine-nucleotide exchange factor, is the intermediate molecule recruited by integrin-linked kinase 1, converging the intracellular signaling toward Rac-1-mediated oxidative vascular dysfunction during pressure overload. Our data demonstrate that biomechanical stress evoked by high blood pressure triggers an integrin-linked kinase 1/betaPIX/Rac-1 signaling, thus generating oxidative vascular dysfunction.

  3. Building Cell Selectivity into CPP-Mediated Strategies

    Directory of Open Access Journals (Sweden)

    Irene Martín

    2010-05-01

    Full Text Available There is a pressing need for more effective and selective therapies for cancer and other diseases. Consequently, much effort is being devoted to the development of alternative experimental approaches based on selective systems, which are designed to be specifically directed against target cells. In addition, a large number of highly potent therapeutic molecules are being discovered. However, they do not reach clinical trials because of their low delivery, poor specificity or their incapacity to bypass the plasma membrane. Cell-penetrating peptides (CPPs are an open door for cell-impermeable compounds to reach intracellular targets. Putting all these together, research is sailing in the direction of the design of systems with the capacity to transport new drugs into a target cell. Some CPPs show cell type specificity while others require modifications or form part of more sophisticated drug delivery systems. In this review article we summarize several strategies for directed drug delivery involving CPPs that have been reported in the literature.

  4. Chemokine-Mediated Choreography of Thymocyte Development and Selection.

    Science.gov (United States)

    Lancaster, Jessica N; Li, Yu; Ehrlich, Lauren I R

    2018-02-01

    As they differentiate, thymocytes encounter spatially restricted cues critical for differentiation and selection of a functional, self-tolerant T cell repertoire. Sequential migration of developing T cells through distinct thymic microenvironments is enforced by the ordered expression of chemokine receptors. Herein, we provide an updated perspective on T cell differentiation through the lens of recent advances that illuminate the dynamics of chemokine-driven thymocyte migration, localization, and interactions with stromal cells. We consider these findings in the context of earlier groundwork exploring the contribution of chemokines to T cell development, recent advances regarding the specificity of chemokine signaling, and novel techniques for evaluating the T cell repertoire. We suggest future research should amalgamate visualization of localized cellular interactions with downstream molecular signals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Impact of blood pressure cuff inflation rates on flow-mediated dilatation and contralateral arm response.

    Science.gov (United States)

    Lin, H-F; Dhindsa, M S; Tarumi, T; Miles, S C; Umpierre, D; Tanaka, H

    2012-01-01

    Flow-mediated dilatation (FMD) is widely used as an index of nitric oxide-mediated vasodilator function, yet its methodology has not been well established. Previous research indicates that a rapid inflation of a blood pressure cuff evokes systemic vasoconstriction, as it was observed even on non-occluded contralateral arm. This would potentially contribute to the variability of FMD readings and complicate the emerging evidence that non-occluded contralateral arm fingertip temperature responses during the FMD procedure may be an indicator of the presence of coronary artery disease. To test the hypotheses that rapid inflation of a blood pressure cuff could reduce FMD values and influence contralateral vasodilatory states, 33 apparently healthy adults (18 males and 15 females, 29±6 years) were studied in two randomized FMD trials. The blood flow-occluding cuff was inflated rapidly (inflation trials (5.9±0.6 vs 5.9±0.4%). There were no differences in reactive hyperaemia (6.4±1.6 vs 6.2±1.7 AU), shear stress (80±20 vs 77±17 dyn cm(-2)) and fingertip temperature rebound (TR; 1.8±1.2 vs 1.9±1.0 °C) between the rapid and slow inflation. Changes in finger temperature on the contralateral (non-occluded) arm were positively associated with those on the occluded arm (r=0.26 to 0.61, Pinflating a blood pressure cuff do not affect FMD and TR response, and that neurovascular-induced vasodilatation of the contralateral arm was not observed regardless of cuff inflation rates.

  6. Selective degeneration of oligodendrocytes mediated by reactive oxygen species.

    Science.gov (United States)

    Griot, C; Vandevelde, M; Richard, A; Peterhans, E; Stocker, R

    1990-01-01

    The mechanism underlying demyelination in inflammatory canine distemper encephalitis is uncertain. Macrophages and their secretory products are thought to play an important effector role in this lesion. Recently, we have shown that anti-canine distemper virus antibodies, known to occur in chronic inflammatory lesions, stimulate macrophages leading to the secretion of reactive oxygen species (ROS). To investigate whether ROS could be involved in demyelination, dog glial cell cultures were exposed to xanthine/xanthine oxidase (X/XO), a system capable of generating O2-. This treatment resulted in a specific time-dependent degeneration and loss of oligodendrocytes, the myelin producing cells of the central nervous system. Initial degeneration was not associated with a decrease in viability of oligodendrocytes as judged by trypan blue and propidium iodide exclusion. Astrocytes and brain macrophages were not affected morphologically by this treatment. Further, an evaluation of the effect of several ROS scavengers, transition metal chelators and inhibitors of poly (ADP-ribose) polymerase suggests that a metal dependent formation of .OH or a similar highly oxidizing species could be responsible for the observed selective damage to oligodendrocytes.

  7. Selected Food Consumption Mediates the Association between Education Level and Metabolic Syndrome in Korean Adults.

    Science.gov (United States)

    Kim, Oh Yoen; Kwak, So-Young; Kim, Boeun; Kim, Young-Sun; Kim, Hye Young; Shin, Min-Jeong

    2017-01-01

    Low socioeconomic status (SES) is linked to higher incidence/mortality of cardiovascular disease, but emerging evidence inconsistently reported that education level, a proxy for SES, is related to cardiovascular risk and metabolic syndrome (MetS) in Koreans. Furthermore, limited information is available on whether dietary components would mediate the relationship between education level and cardiovascular risk. We hypothesized that selected food consumption mediates the association between education level and MetS prevalence. Data from the Korea National Health and Nutritional Examination Survey (2008-2011) were included in cross-sectional analyses (n = 11,029, 30-64 years). The possible mediating effect of selected food groups (fruits, raw vegetables, red meat, milk, and soft drinks) on the association between education level and MetS was tested using a multiple mediation model. Education level was negatively associated with MetS prevalence. The association between lower education level and higher MetS prevalence was partially mediated by selected food consumption (lower intakes of fruit, red meat and milk; higher intakes of vegetable and soft drink) after adjusted for covariates. Gender also modified the association between education level and MetS prevalence that was more prominent in women than in men. Selected food consumption substantially contributes to the association between education level and MetS in Korean adults, especially among women. © 2017 S. Karger AG, Basel.

  8. Is the Relationship between Race and Continuous Positive Airway Pressure Adherence Mediated by Sleep Duration?

    Science.gov (United States)

    Billings, Martha E.; Rosen, Carol L.; Wang, Rui; Auckley, Dennis; Benca, Ruth; Foldvary-Schaefer, Nancy; Iber, Conrad; Zee, Phyllis; Redline, Susan; Kapur, Vishesh K.

    2013-01-01

    Study Objectives: Black race has been associated with decreased continuous positive airway pressure (CPAP) adherence. Short sleep duration, long sleep latency, and insomnia complaints may affect CPAP adherence as they affect sleep and opportunity to use CPAP. We assessed whether self-reported sleep measures were associated with CPAP adherence and if racial variations in these sleep characteristics may explain racial differences in CPAP adherence. Design: Analysis of data from a randomized controlled trial (HomePAP), which investigated home versus laboratory-based diagnosis and treatment of obstructive sleep apnea. Setting: Seven American Academy of Sleep Medicine-accredited sleep centers in five cities in the United States. Patients or Participants: Enrolled subjects (n = 191) with apnea-hypopnea index ≥ 15 and sleepiness (Epworth Sleepiness Scale > 12). Interventions: N/A. Measurements and Results: Multivariable regression was used to assess if subjective sleep measures and symptoms predicted 3-mo CPAP use. Mediation analysis was used to assess if sleep measures mediated the association of race with CPAP adherence. Black participants reported shorter sleep duration and longer sleep latency at baseline than white and Hispanic participants. Shorter sleep duration and longer sleep latency predicted worse CPAP adherence. Sleep duration mediated the association of black race with lower CPAP adherence. However, insomnia symptoms were not associated with race or CPAP adherence. Conclusions: Among subjects with similar severity of obstructive sleep apnea and sleepiness, baseline self-reported sleep duration and latency, but not perceived insomnia, predicted CPAP adherence over 3 mo. Sleep duration explains some of the observed differences in CPAP use by race. Sleep duration and latency should be considered when evaluating poor CPAP adherence. Clinical Trial Information: Portable Monitoring for Diagnosis and Management of Sleep Apnea (HomePAP) URL: http

  9. Origin of serpin-mediated regulation of coagulation and blood pressure.

    Directory of Open Access Journals (Sweden)

    Yunjie Wang

    Full Text Available Vertebrates evolved an endothelium-lined hemostatic system and a pump-driven pressurized circulation with a finely-balanced coagulation cascade and elaborate blood pressure control over the past 500 million years. Genome analyses have identified principal components of the ancestral coagulation system, however, how this complex trait was originally regulated is largely unknown. Likewise, little is known about the roots of blood pressure control in vertebrates. Here we studied three members of the serpin superfamily that interfere with procoagulant activity and blood pressure of lampreys, a group of basal vertebrates. Angiotensinogen from these jawless fish was found to fulfill a dual role by operating as a highly selective thrombin inhibitor that is activated by heparin-related glycosaminoglycans, and concurrently by serving as source of effector peptides that activate type 1 angiotensin receptors. Lampreys, uniquely among vertebrates, thus use angiotensinogen for interference with both coagulation and osmo- and pressure regulation. Heparin cofactor II from lampreys, in contrast to its paralogue angiotensinogen, is preferentially activated by dermatan sulfate, suggesting that these two serpins affect different facets of thrombin's multiple roles. Lampreys also express a lineage-specific serpin with anti-factor Xa activity, which demonstrates that another important procoagulant enzyme is under inhibitory control. Comparative genomics suggests that orthologues of these three serpins were key components of the ancestral hemostatic system. It appears that, early in vertebrate evolution, coagulation and osmo- and pressure regulation crosstalked through antiproteolytically active angiotensinogen, a feature that was lost during vertebrate radiation, though in gnathostomes interplay between these traits is effective.

  10. Pressure-mediated versus pharmacologic treatment of radial artery spasm during cardiac catheterisation: a randomised pilot study.

    Science.gov (United States)

    Collet, Carlos; Corral, Juan M; Cavalcante, Rafael; Tateishi, Hiroki; Belzarez, Oward; Ribamar Costa, Jose; Costa, Ricardo; Chamié, Daniel; Onuma, Yoshinobu; de Winter, Robbert J; Abizaid, Alexandre; Serruys, Patrick W

    2017-04-07

    The aim of the study was to determine the effectiveness of a novel strategy to treat radial artery spasm (RAS). We conducted a prospective, randomised, single-centre, open-label trial comparing a novel strategy of pressure-mediated dilatation versus intra-arterial administration of a combination of nitroglycerine plus verapamil for the treatment of RAS. The primary endpoint was radial artery intraluminal diameter acute gain assessed by quantitative radial angiography. After screening two hundred and twenty consecutive cases, twenty patients presented with RAS and were randomised 1:1 to either strategy. Overall the mean age was 60.8±11.5 years and 53% were females. Pre-treatment angiographic characteristics were similar between the groups. The primary endpoint of radial artery acute gain was significantly greater in the pressure-mediated dilatation group (0.85±0.46 mm vs. 0.03±0.24 mm, p<0.001). Blood pressure drop was significantly lower in the pressure-mediated dilatation group (ΔBP -3.8±24 vs. -31.6±19 mmHg, p<0.001). There was one case of radial artery occlusion in the pressure-mediated dilatation group at follow-up. Short-duration pain was observed during the application of pressure. Pressure-mediated dilatation for the treatment of RAS was feasible, with superior angiographic results compared to a pharmacologic vasodilator strategy, with no impact on blood pressure. This novel approach proved to be safe and effective and should be tested in a large randomised trial.

  11. Peer pressure and thai amateur golfers' gambling on their games: the mediating effect of golf self-efficacy.

    Science.gov (United States)

    Ariyabuddhiphongs, Vanchai; Promsakha Na Sakolnakorn, Chomnad

    2014-09-01

    Our study hypothesizes that Thai amateur golfers gamble on their game because of peer pressure and their golf self-efficacy. To support our hypothesis, we conducted a study to examine the mediating effect of golf self-efficacy on the peer pressure-golf gambling relationship among 387 amateur golfers in Thailand. Peer pressure was operationally defined as fellow players' influence on the individual golfer to gamble; golf self-efficacy as the judgment of the golfer's skills to play golf; and golf gambling as the frequency and amounts of gambling. Regression analysis with bootstrapping was used to test the mediation effect of golf self-efficacy on the peer pressure-golf gambling relationship. The results support our hypothesis; peer pressure predicted golf gambling, and the indirect effect of peer pressure to golf gambling through the mediation of golf self-efficacy was significant. The results support the influence of peer pressure on gambling, and the social cognitive theory reciprocal relationship model.

  12. Selection of High Strength Encapsulant for MEMS Devices Undergoing High Pressure Packaging

    OpenAIRE

    Hamzah, A.A.; Husaini, Y.; Majlis, B.Y.; Ahmad, I.

    2007-01-01

    Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/EDA-Publishing); International audience; Deflection behavior of several encapsulant materials under uniform pressure was studied to determine the best encapsulant for MEMS device. Encapsulation is needed to protect movable parts of MEMS devices during high pressure transfer molded packaging process. The selected encapsulant material has to have surface deflection of less than 5 ?m under 100 atm vertical loading. Deflec...

  13. BMI mediates the association between low educational level and higher blood pressure during pregnancy in Japan.

    Science.gov (United States)

    Jwa, Seung Chik; Fujiwara, Takeo; Hata, Akira; Arata, Naoko; Sago, Haruhiko; Ohya, Yukihiro

    2013-04-25

    Research investigating the association between socioeconomic status (SES) and blood pressure (BP) during pregnancy is limited and its underlying pathway is unknown. The aim of this study was to investigate the mediators of the association between educational level as an indicator of the SES and BP in early and mid-pregnancy among Japanese women. Nine hundred and twenty-three pregnant women in whom BP was measured before 16 weeks and at 20 weeks of gestation were enrolled in this study. Maternal educational levels were categorized into three groups: high (university or higher), mid (junior college), and low (junior high school, high school, or vocational training school). The low educational group had higher systolic (low vs. high, difference = 2.39 mmHg, 95% confidence interval [CI]: 0.59 to 4.19) and diastolic BP levels (low vs. high, difference = 0.74 mmHg, 95% CI: -0.52 to 1.99) in early pregnancy. However, the same associations were not found after adjustment for pre-pregnancy body mass index (BMI). BP reduction was observed in mid-pregnancy in all three educational groups and there was no association between educational level and pregnancy-induced hypertension. In Japanese women, the low educational group showed higher BP during pregnancy than the mid or high educational groups. Pre-pregnancy BMI mediates the association between educational level and BP.

  14. Is the relationship between race and continuous positive airway pressure adherence mediated by sleep duration?

    Science.gov (United States)

    Billings, Martha E; Rosen, Carol L; Wang, Rui; Auckley, Dennis; Benca, Ruth; Foldvary-Schaefer, Nancy; Iber, Conrad; Zee, Phyllis; Redline, Susan; Kapur, Vishesh K

    2013-02-01

    Black race has been associated with decreased continuous positive airway pressure (CPAP) adherence. Short sleep duration, long sleep latency, and insomnia complaints may affect CPAP adherence as they affect sleep and opportunity to use CPAP. We assessed whether self-reported sleep measures were associated with CPAP adherence and if racial variations in these sleep characteristics may explain racial differences in CPAP adherence. Analysis of data from a randomized controlled trial (HomePAP), which investigated home versus laboratory-based diagnosis and treatment of obstructive sleep apnea. Seven American Academy of Sleep Medicine-accredited sleep centers in five cities in the United States. Enrolled subjects (n = 191) with apnea-hypopnea index ≥ 15 and sleepiness (Epworth Sleepiness Scale > 12). N/A. Multivariable regression was used to assess if subjective sleep measures and symptoms predicted 3-mo CPAP use. Mediation analysis was used to assess if sleep measures mediated the association of race with CPAP adherence. Black participants reported shorter sleep duration and longer sleep latency at baseline than white and Hispanic participants. Shorter sleep duration and longer sleep latency predicted worse CPAP adherence. Sleep duration mediated the association of black race with lower CPAP adherence. However, insomnia symptoms were not associated with race or CPAP adherence. Among subjects with similar severity of obstructive sleep apnea and sleepiness, baseline self-reported sleep duration and latency, but not perceived insomnia, predicted CPAP adherence over 3 mo. Sleep duration explains some of the observed differences in CPAP use by race. Sleep duration and latency should be considered when evaluating poor CPAP adherence. PORTABLE MONITORING FOR DIAGNOSIS AND MANAGEMENT OF SLEEP APNEA (HOMEPAP) URL: http://clinicaltrials.gov/show/NCT00642486. NIH clinical trials registry number: NCT00642486.

  15. Parasite-mediated sexual selection and species divergence in Lake Victoria cichlid fish

    NARCIS (Netherlands)

    Maan, Martine E.; Van Rooijen, Anne M. C.; Van Alphen, Jacques J. M.; Seehausen, Ole

    We investigate the role of parasite-mediated sexual selection in the divergence of two species of Lake Victoria cichlids. Pundamilia pundamilia and Pundamilia nyererei represent a common pattern of male nuptial colour divergence between haplochromine sister species: metallic grey-blue in P.

  16. Blood pressure lowering effect of olive is mediated through calcium channel blockade.

    Science.gov (United States)

    Gilani, Anwarul Hassan; Khan, Arif-Ullah; Shah, Abdul Jabbar; Connor, John; Jabeen, Qaiser

    2005-12-01

    Olive (Olea europea) is used in traditional medicine as a remedy for hypertension. The aqueous-methanolic crude extract of O. europea fruit (OeF.Cr) was studied in anaesthetized rats and its possible mechanism was elucidated using isolated cardiovascular preparations. Intravenous administration of OeF.Cr produced a dose-dependent (30-100 mg/kg) fall in arterial blood pressure in normotensive anaesthetized rats. This effect remained unaltered in atropinized animals. In the in vitro studies OeF.Cr (0.1-3.0 mg/ml) inhibited spontaneously beating guinea-pig atria. Moreover, it relaxed K+ and/or phenylephrine-induced contractions of rabbit aortic preparations over a dose range of 0.1-3.0 mg/ml, suggesting calcium channel blockade (CCB). The CCB effect was confirmed when pretreatment of the vascular preparations with OeF.Cr produced a dose-dependent rightward shift of the Ca2+ dose-response curves, similar to verapamil. These results suggest that the blood pressure lowering effect of olive is mediated through CCB, justifying its use in hypertension.

  17. Adaptive evolution in locomotor performance: How selective pressures and functional relationships produce diversity.

    Science.gov (United States)

    Scales, Jeffrey A; Butler, Marguerite A

    2016-01-01

    Despite the complexity of nature, most comparative studies of phenotypic evolution consider selective pressures in isolation. When competing pressures operate on the same system, it is commonly expected that trade-offs will occur that will limit the evolution of phenotypic diversity, however, it is possible that interactions among selective pressures may promote diversity instead. We explored the evolution of locomotor performance in lizards in relation to possible selective pressures using the Ornstein-Uhlenbeck process. Here, we show that a combination of selection based on foraging mode and predator escape is required to explain variation in performance phenotypes. Surprisingly, habitat use contributed little explanatory power. We find that it is possible to evolve very different abilities in performance which were previously thought to be tightly correlated, supporting a growing literature that explores the many-to-one mapping of morphological design. Although we generally find the expected trade-off between maximal exertion and speed, this relationship surprisingly disappears when species experience selection for both performance types. We conclude that functional integration need not limit adaptive potential, and that an integrative approach considering multiple major influences on a phenotype allows a more complete understanding of adaptation and the evolution of diversity. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  18. In Arabidopsis thaliana codon volatility scores reflect GC3 composition rather than selective pressure

    Directory of Open Access Journals (Sweden)

    O'Connell Mary J

    2012-07-01

    Full Text Available Abstract Background Synonymous codon usage bias has typically been correlated with, and attributed to translational efficiency. However, there are other pressures on genomic sequence composition that can affect codon usage patterns such as mutational biases. This study provides an analysis of the codon usage patterns in Arabidopsis thaliana in relation to gene expression levels, codon volatility, mutational biases and selective pressures. Results We have performed synonymous codon usage and codon volatility analyses for all genes in the A. thaliana genome. In contrast to reports for species from other kingdoms, we find that neither codon usage nor volatility are correlated with selection pressure (as measured by dN/dS, nor with gene expression levels on a genome wide level. Our results show that codon volatility and usage are not synonymous, rather that they are correlated with the abundance of G and C at the third codon position (GC3. Conclusions Our results indicate that while the A. thaliana genome shows evidence for synonymous codon usage bias, this is not related to the expression levels of its constituent genes. Neither codon volatility nor codon usage are correlated with expression levels or selective pressures but, because they are directly related to the composition of G and C at the third codon position, they are the result of mutational bias. Therefore, in A. thaliana codon volatility and usage do not result from selection for translation efficiency or protein functional shift as measured by positive selection.

  19. Positive Selection Pressure Drives Variation on the Surface-Exposed Variable Proteins of the Pathogenic Neisseria.

    Science.gov (United States)

    Wachter, Jenny; Hill, Stuart

    2016-01-01

    Pathogenic species of Neisseria utilize variable outer membrane proteins to facilitate infection and proliferation within the human host. However, the mechanisms behind the evolution of these variable alleles remain largely unknown due to analysis of previously limited datasets. In this study, we have expanded upon the previous analyses to substantially increase the number of analyzed sequences by including multiple diverse strains, from various geographic locations, to determine whether positive selective pressure is exerted on the evolution of these variable genes. Although Neisseria are naturally competent, this analysis indicates that only intrastrain horizontal gene transfer among the pathogenic Neisseria principally account for these genes exhibiting linkage equilibrium which drives the polymorphisms evidenced within these alleles. As the majority of polymorphisms occur across species, the divergence of these variable genes is dependent upon the species and is independent of geographical location, disease severity, or serogroup. Tests of neutrality were able to detect strong selection pressures acting upon both the opa and pil gene families, and were able to locate the majority of these sites within the exposed variable regions of the encoded proteins. Evidence of positive selection acting upon the hypervariable domains of Opa contradicts previous beliefs and provides evidence for selection of receptor binding. As the pathogenic Neisseria reside exclusively within the human host, the strong selection pressures acting upon both the opa and pil gene families provide support for host immune system pressure driving sequence polymorphisms within these variable genes.

  20. Selection pressure transforms the nature of social dilemmas in adaptive networks

    International Nuclear Information System (INIS)

    Van Segbroeck, Sven; Lenaerts, Tom; Santos, Francisco C; Pacheco, Jorge M

    2011-01-01

    We have studied the evolution of cooperation in structured populations whose topology coevolves with the game strategies of the individuals. Strategy evolution proceeds according to an update rule with a free parameter, which measures the selection pressure. We explore how this parameter affects the interplay between network dynamics and strategy dynamics. A dynamical network topology can influence the strategy dynamics in two ways: (i) by modifying the expected payoff associated with each strategy and (ii) by reshaping the imitation network that underlies the evolutionary process. We show here that the selection pressure tunes the relative contribution of each of these two forces to the final outcome of strategy evolution. The dynamics of the imitation network plays only a minor role under strong selection, but becomes the dominant force under weak selection. We demonstrate how these findings constitute a mechanism supporting cooperative behavior.

  1. Disagreement in primary study selection between systematic reviews on negative pressure wound therapy

    OpenAIRE

    Peinemann, Frank; McGauran, Natalie; Sauerland, Stefan; Lange, Stefan

    2008-01-01

    Abstract Background Primary study selection between systematic reviews is inconsistent, and reviews on the same topic may reach different conclusions. Our main objective was to compare systematic reviews on negative pressure wound therapy (NPWT) regarding their agreement in primary study selection. Methods This retrospective analysis was conducted within the framework of a systematic review (a full review and a subsequent rapid report) on NPWT prepared by the Institute for Quality and Efficie...

  2. Selection Pressures on Special Education Teacher Preparation: Issues Shaping Our Future

    Science.gov (United States)

    Dukes, Charles; Darling, Sharon M.; Doan, Kim

    2014-01-01

    In this introduction to the special issue on evolving changes in our field, we have intentionally chosen to use the power of a vastly different metaphor to promote deep reflection. Specifically, we will introduce the notion of selection pressures and its impact on an evolutionary process, illustrating how special education teacher education has…

  3. Determination of Polychlorinated Biphenyls in Soil and Sediment by Selective Pressurized Liquid Extraction with Immunochemical Detection

    Science.gov (United States)

    A selective liquid pressurized extraction (SPLE) method was developed as a streamlined sample preparation/cleanup procedure for determining Aroclors and coplanar polychlorinated biphenyls (PCBs) in soil and sediment matrices. The SPLE method was coupled with an enzyme-linked imm...

  4. The selection pressures induced non-smooth infectious disease model and bifurcation analysis

    International Nuclear Information System (INIS)

    Qin, Wenjie; Tang, Sanyi

    2014-01-01

    Highlights: • A non-smooth infectious disease model to describe selection pressure is developed. • The effect of selection pressure on infectious disease transmission is addressed. • The key factors which are related to the threshold value are determined. • The stabilities and bifurcations of model have been revealed in more detail. • Strategies for the prevention of emerging infectious disease are proposed. - Abstract: Mathematical models can assist in the design strategies to control emerging infectious disease. This paper deduces a non-smooth infectious disease model induced by selection pressures. Analysis of this model reveals rich dynamics including local, global stability of equilibria and local sliding bifurcations. Model solutions ultimately stabilize at either one real equilibrium or the pseudo-equilibrium on the switching surface of the present model, depending on the threshold value determined by some related parameters. Our main results show that reducing the threshold value to a appropriate level could contribute to the efficacy on prevention and treatment of emerging infectious disease, which indicates that the selection pressures can be beneficial to prevent the emerging infectious disease under medical resource limitation

  5. Selective cytotoxicity of indirect nonequilibrium atmospheric pressure plasma against ovarian clear-cell carcinoma.

    Science.gov (United States)

    Utsumi, Fumi; Kajiyama, Hiroaki; Nakamura, Kae; Tanaka, Hiromasa; Hori, Masaru; Kikkawa, Fumitaka

    2014-01-01

    Ovarian clear cell carcinoma (CCC) is a histological type of epithelial ovarian cancer that is less responsive to chemotherapy and associated with a poorer prognosis than serous and endometrioid carcinoma. Non-thermal atmospheric pressure plasma which produces reactive species has recently led to an explosion of research in plasma medicine. Plasma treatment can be applied to cancer treatment to induce apoptosis and tumor growth arrest. Furthermore, recent studies have shown that a medium exposed to plasma also has an anti-proliferative effect against cancer in the absence of direct exposure to plasma. In this study, we confirmed whether this indirect plasma has an anti-tumor effect against CCC, and investigated whether this efficacy is selective for cancer cells. Non-thermal atmospheric pressure plasma induced apoptosis in CCC cells, while human peritoneal mesothelial cells remained viable. Non-thermal atmospheric pressure plasma exhibits selective cytotoxicity against CCC cells which are resistant to chemotherapy.

  6. Picture Yourself Healthy-How Users Select Mediated Images to Shape Health Intentions and Behaviors.

    Science.gov (United States)

    Wilson, Brianna; Knobloch-Westerwick, Silvia; Robinson, Melissa J

    2018-02-20

    Hypotheses on how selective viewing of mediated images may sustain eating habits and aid healthier eating were derived from the Selective Exposure Self- and Affect Management model. The model posits that individuals select to view media to manage their self-concepts-and that this exposure affects subsequent intentions and behaviors. Participants (N = 265) selectively viewed Instagram-like postings featuring healthy or unhealthy food imagery. Beforehand, participants reported habits and perceived expert recommendations regarding food intake. After viewing postings, participants chose gift cards representing healthy or unhealthy food purchases and indicated food intake intentions. Results show that existing eating behavior predicts selective exposure to healthy or unhealthy food imagery, which in turn shapes gift card choices and (both healthy and unhealthy) food intake intentions.

  7. Elevated pressure, a novel cancer therapeutic tool for sensitizing cisplatin-mediated apoptosis in A549

    International Nuclear Information System (INIS)

    Oh, Sangnam; Kim, Yanghee; Kim, Joonhee; Kwon, Daeho; Lee, Eunil

    2010-01-01

    Research highlights: → Sensitized apoptosis in cancer cells stimulated by EP precondition with p53 dependence. → EP attenuates several CDDP-resistance mechanisms. → No harmful effect of EP on normal fibroblasts. -- Abstract: Intensive cancer therapy strategies have thus far focused on sensitizing cancer cells to anticancer drug-mediated apoptosis to overcome drug resistance, and this strategy has led to more effective cancer therapeutics. Cisplatin (cis-diamminedichloroplatinum(II), CDDP) is an effective anticancer drug used to treat many types of cancer, including non-small cell lung carcinoma (NSCLC), and can be used in combination with various chemicals to enhance cancer cell apoptosis. Here, we introduce the use of elevated pressure (EP) in combination with CDDP for cancer treatment and explore the effects of EP on CDDP-mediated apoptosis in NSCLC cells. Our findings demonstrate that preconditioning NSCLC cells with EP sensitizes cells for CDDP-induced apoptosis. Enhanced apoptosis was dependent on p53 and HO-1 expression, and was associated with increased DNA damage and down-regulation of genes involved in nucleotide excision repair. The transcriptional levels of transporter proteins indicated that the mechanism by which EP-induced CDDP sensitization was intracellular drug accumulation. The protein levels of some antioxidants, such as hemeoxygenase-1 (HO-1), glutathione (GSH) and glutathione peroxidase (Gpx), were decreased in A549 cells exposed to EP via the down-regulation of the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf-2). Furthermore, normal human fibroblasts were resistant to EP treatment, with no elevated DNA damage or apoptosis. Collectively, these data show that administration of EP is a potential adjuvant tool for CDDP-based chemosensitivity of lung cancer cells that may reduce drug resistance.

  8. Stress, Time Pressure, Strategy Selection and Math Anxiety in Mathematics: A Review of the Literature.

    Science.gov (United States)

    Caviola, Sara; Carey, Emma; Mammarella, Irene C; Szucs, Denes

    2017-01-01

    We review how stress induction, time pressure manipulations and math anxiety can interfere with or modulate selection of problem-solving strategies (henceforth "strategy selection") in arithmetical tasks. Nineteen relevant articles were identified, which contain references to strategy selection and time limit (or time manipulations), with some also discussing emotional aspects in mathematical outcomes. Few of these take cognitive processes such as working memory or executive functions into consideration. We conclude that due to the sparsity of available literature our questions can only be partially answered and currently there is not much evidence of clear associations. We identify major gaps in knowledge and raise a series of open questions to guide further research.

  9. High hunting pressure selects for earlier birth date: Wild boar as a case study

    Science.gov (United States)

    Gamelon, M.; Besnard, A.; Gaillard, J.-M.; Servanty, S.; Baubet, E.; Brandt, S.; Gimenez, O.

    2011-01-01

    Exploitation by humans affects the size and structure of populations. This has evolutionary and demographic consequences that have typically being studied independent of one another. We here applied a framework recently developed applying quantitative tools from population ecology and selection gradient analysis to quantify the selection on a quantitative trait-birth date-through its association with multiple fitness components. From the long-term monitoring (22 years) of a wild boar (Sus scrofa scrofa) population subject to markedly increasing hunting pressure, we found that birth dates have advanced by up to 12 days throughout the study period. During the period of low hunting pressure, there was no detectable selection. However, during the period of high hunting pressure, the selection gradient linking breeding probability in the first year of life to birth date was negative, supporting current life-history theory predicting selection for early births to reproduce within the first year of life with increasing adult mortality. ?? 2011 The Author(s). Evolution?? 2011 The Society for the Study of Evolution..

  10. Mediating effects of nocturnal blood pressure and morning surge on the contributions of arterial stiffness and sodium intake to morning blood pressure: A path analysis.

    Science.gov (United States)

    Lee, Hyung Tak; Park, Jin-Kyu; Choi, Sung Yong; Choi, Bo Youl; Kim, Mi Kyung; Mori, Mari; Yamori, Yukio; Lim, Young Hyo; Shin, Jinho

    2016-01-01

    The aim of this study was to evaluate the mediating effects of nocturnal blood pressure (BP) and morning surge on the contribution of arterial stiffness and sodium intake to morning BP in a middle-aged general population. The study included 124 subjects aged 30-59 years, from rural Yeoju County, Gyeonggi Province, South Korea. Ambulatory BP monitoring, 24 h urinary sodium excretion (24 h UNa) and brachial-ankle pulse wave velocity (baPWV) measurements were performed in all subjects. The mean ± SD age was 48.1 ± 8.2 years and the proportion of male subjects was 41.1%. After adjusting for covariates, morning systolic blood pressure (SBP) was significantly correlated with morning surge [coefficient = 0.761, 95% confidence interval (CI) 0.651-0.872, p morning SBP. The indirect effect mediated by nocturnal SBP was statistically significant (0.054, p = 0.005), but the indirect effect mediated by the morning surge was not significant. The 24 h UNa had no significant direct or indirect effects on morning SBP. baPWV had significant direct and indirect effects on morning SBP. The indirect effect was mediated by nocturnal SBP, but not by morning surge. The 24 h UNa had neither significant direct nor indirect effects on morning SBP.

  11. Quantitative analysis of mutation and selection pressures on base composition skews in bacterial chromosomes

    Directory of Open Access Journals (Sweden)

    Chen Carton W

    2007-08-01

    Full Text Available Abstract Background Most bacterial chromosomes exhibit asymmetry of base composition with respect to leading vs. lagging strands (GC and AT skews. These skews reflect mainly those in protein coding sequences, which are driven by asymmetric mutation pressures during replication and transcription (notably asymmetric cytosine deamination plus subsequent selection for preferred structures, signals, amino acid or codons. The transcription-associated effects but not the replication-associated effects contribute to the overall skews through the uneven distribution of the coding sequences on the leading and lagging strands. Results Analysis of 185 representative bacterial chromosomes showed diverse and characteristic patterns of skews among different clades. The base composition skews in the coding sequences were used to derive quantitatively the effect of replication-driven mutation plus subsequent selection ('replication-associated pressure', RAP, and the effect of transcription-driven mutation plus subsequent selection at translation level ('transcription-associate pressure', TAP. While different clades exhibit distinct patterns of RAP and TAP, RAP is absent or nearly absent in some bacteria, but TAP is present in all. The selection pressure at the translation level is evident in all bacteria based on the analysis of the skews at the three codon positions. Contribution of asymmetric cytosine deamination was found to be weak to TAP in most phyla, and strong to RAP in all the Proteobacteria but weak in most of the Firmicutes. This possibly reflects the differences in their chromosomal replication machineries. A strong negative correlation between TAP and G+C content and between TAP and chromosomal size were also revealed. Conclusion The study reveals the diverse mutation and selection forces associated with replication and transcription in various groups of bacteria that shape the distinct patterns of base composition skews in the chromosomes during

  12. Grape polyphenols reduce blood pressure and increase flow-mediated vasodilation in men with metabolic syndrome.

    Science.gov (United States)

    Barona, Jacqueline; Aristizabal, Juan C; Blesso, Christopher N; Volek, Jeff S; Fernandez, Maria Luz

    2012-09-01

    We evaluated the effects of grape polyphenols in individuals classified with metabolic syndrome (MetS). Men (n = 24) aged 30-70 y were randomly assigned to consume either a freeze-dried grape polyphenol powder (GRAPE) or a placebo for 30 d in a double-blind, crossover design, separated by a 3-wk washout period. Participants were asked to maintain their usual diet and physical activity during the study and abstain from consuming polyphenol-rich foods. MetS criteria including blood pressure (BP) and markers of vascular endothelial function including brachial artery flow-mediated vasodilation (FMD), plasma total nitrite + nitrate (NOx) to estimate NO production, plasma soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured at the end of each dietary period. Systolic BP (P GRAPE compared with the placebo period. In addition, changes in sVCAM-1 concentrations between periods were positively correlated with changes in systolic BP (r = 0.45; P GRAPE and placebo periods. These results suggest that GRAPE polyphenols may potentiate vasorelaxation and reduce BP and circulating cell adhesion molecules, resulting in improvements in vascular function.

  13. Pressure induced phase transition behavior in selected A2B3 type topological insulator minerals

    Science.gov (United States)

    Liu, H.; Liu, L. L.

    2013-12-01

    In this presentation, the recently projects from HIT Overseas Collaborative Base at Argonne, including phase transitions of selected A2B3 type topological insulator minerals upon compression at room and low temperature, studies on amorphous and melt samples under high pressure conditions using synchrotron x-ray 3D imaging techniques in diamond anvil cell and large volume press, etc, will be introduced. The advance of synchrotron greatly improved our knowledge of the minerals under pressure, which is critical for understanding the evolution of Earth.

  14. Genome-wide scans between two honeybee populations reveal putative signatures of human-mediated selection.

    Science.gov (United States)

    Parejo, M; Wragg, D; Henriques, D; Vignal, A; Neuditschko, M

    2017-12-01

    Human-mediated selection has left signatures in the genomes of many domesticated animals, including the European dark honeybee, Apis mellifera mellifera, which has been selected by apiculturists for centuries. Using whole-genome sequence information, we investigated selection signatures in spatially separated honeybee subpopulations (Switzerland, n = 39 and France, n = 17). Three different test statistics were calculated in windows of 2 kb (fixation index, cross-population extended haplotype homozygosity and cross-population composite likelihood ratio) and combined into a recently developed composite selection score. Applying a stringent false discovery rate of 0.01, we identified six significant selective sweeps distributed across five chromosomes covering eight genes. These genes are associated with multiple molecular and biological functions, including regulation of transcription, receptor binding and signal transduction. Of particular interest is a selection signature on chromosome 1, which corresponds to the WNT4 gene, the family of which is conserved across the animal kingdom with a variety of functions. In Drosophila melanogaster, WNT4 alleles have been associated with differential wing, cross vein and abdominal phenotypes. Defining phenotypic characteristics of different Apis mellifera ssp., which are typically used as selection criteria, include colour and wing venation pattern. This signal is therefore likely to be a good candidate for human mediated-selection arising from different applied breeding practices in the two managed populations. © 2017 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.

  15. Selection and static calibration of the Marsh J1678 pressure gauge

    Science.gov (United States)

    Oxendine, Charles R.; Smith, Howard W.

    1993-01-01

    During the experimental testing of the ultralight, it was determined that a pressure gauge would be required to monitor the simulated flight loads. After analyzing several factors, which are indicated in the discussion section of this report, the Marsh J1678 pressure gauge appeared to be the prominent candidate for the task. However, prior to the final selection, the Marsh pressure gauge was calibrated twice by two different techniques. As a result of the calibration, the Marsh gauge was selected as the appropriate measuring device during the structural testing of the ultralight. Although, there are commerical pressure gauges available on the market that would have proven to be more efficient and accurate. However, in order to obtain these characteristics in a gauge, one has to pay the price on the price tag, and this value is an exponential function of the degree of accuracy efficiency, precision, and many other features that may be designed into the gauge. After analyzing the extent of precision and accuracy that would be required, a more expensive gauge wouldn't have proven to be a financial benefit towards the outcome of the experiment.

  16. Highly efficient and selective pressure-assisted photon-induced polymerization of styrene

    Energy Technology Data Exchange (ETDEWEB)

    Guan, Jiwen [Department of Physics and Astronomy, University of Western Ontario, London, Ontario N6A 3K7 (Canada); Song, Yang, E-mail: yang.song@uwo.ca [Department of Physics and Astronomy, University of Western Ontario, London, Ontario N6A 3K7 (Canada); Department of Chemistry, University of Western Ontario, London, Ontario N6A 5B7 (Canada)

    2016-06-07

    The polymerization process of condensed styrene to produce polystyrene as an industrially important polymeric material was investigated using a novel approach by combining external compression with ultraviolet radiation. The reaction evolution was monitored as a function of time and the reaction products were characterized by in situ Fourier transform infrared spectroscopy. By optimizing the loading pressures, we observed highly efficient and selective production of polystyrene of different tacticities. Specifically, at relatively low loading pressures, infrared spectra suggest that styrene monomers transform to amorphous atactic polystyrene (APS) with minor crystalline isotactic polystyrene. In contrast, APS was found to be the sole product when polymerization occurs at relatively higher loading pressures. The time-dependent reaction profiles allow the examination of the polymerization kinetics by analyzing the rate constant and activation volume as a function of pressure. As a result, an optimized pressure condition, which allows a barrierless reaction to proceed, was identified and attributed to the very desirable reaction yield and kinetics. Finally, the photoinitiated reaction mechanism and the growth geometry of the polymer chains were investigated from the energy diagram of styrene and by the topology analysis of the crystal styrene. This study shows strong promise to produce functional polymeric materials in a highly efficient and controlled manner.

  17. Peptide-Based Selective Inhibitors of Matrix Metalloproteinase-Mediated Activities

    Directory of Open Access Journals (Sweden)

    Margaret W. Ndinguri

    2012-11-01

    Full Text Available The matrix metalloproteinases (MMPs exhibit a broad array of activities, some catalytic and some non-catalytic in nature. An overall lack of selectivity has rendered small molecule, active site targeted MMP inhibitors problematic in execution. Inhibitors that favor few or individual members of the MMP family often take advantage of interactions outside the enzyme active site. We presently focus on peptide-based MMP inhibitors and probes that do not incorporate conventional Zn2+ binding groups. In some cases, these inhibitors and probes function by binding only secondary binding sites (exosites, while others bind both exosites and the active site. A myriad of MMP mediated-activities beyond selective catalysis can be inhibited by peptides, particularly cell adhesion, proliferation, motility, and invasion. Selective MMP binding peptides comprise highly customizable, unique imaging agents. Areas of needed improvement for MMP targeting peptides include binding affinity and stability.

  18. Shared Selective Pressures on Fungal and Human Metabolic Pathways Lead to Divergent yet Analogous Genetic Responses.

    Science.gov (United States)

    Eidem, Haley R; McGary, Kriston L; Rokas, Antonis

    2015-06-01

    Reduced metabolic efficiency, toxic intermediate accumulation, and deficits of molecular building blocks, which all stem from disruptions of flux through metabolic pathways, reduce organismal fitness. Although these represent shared selection pressures across organisms, the genetic signatures of the responses to them may differ. In fungi, a frequently observed signature is the physical linkage of genes from the same metabolic pathway. In contrast, human metabolic genes are rarely tightly linked; rather, they tend to show tissue-specific coexpression. We hypothesized that the physical linkage of fungal metabolic genes and the tissue-specific coexpression of human metabolic genes are divergent yet analogous responses to the range of selective pressures imposed by disruptions of flux. To test this, we examined the degree to which the human homologs of physically linked metabolic genes in fungi (fungal linked homologs or FLOs) are coexpressed across six human tissues. We found that FLOs are significantly more correlated in their expression profiles across human tissues than other metabolic genes. We obtained similar results in analyses of the same six tissues from chimps, gorillas, orangutans, and macaques. We suggest that when selective pressures remain stable across large evolutionary distances, evidence of selection in a given evolutionary lineage can become a highly reliable predictor of the signature of selection in another, even though the specific adaptive response in each lineage is markedly different. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Adaptation to fluctuating temperatures in an RNA virus is driven by the most stringent selective pressure.

    Directory of Open Access Journals (Sweden)

    María Arribas

    Full Text Available The frequency of change in the selective pressures is one of the main factors driving evolution. It is generally accepted that constant environments select specialist organisms whereas changing environments favour generalists. The particular outcome achieved in either case also depends on the relative strength of the selective pressures and on the fitness costs of mutations across environments. RNA viruses are characterized by their high genetic diversity, which provides fast adaptation to environmental changes and helps them evade most antiviral treatments. Therefore, the study of the adaptive possibilities of RNA viruses is highly relevant for both basic and applied research. In this study we have evolved an RNA virus, the bacteriophage Qβ, under three different temperatures that either were kept constant or alternated periodically. The populations obtained were analyzed at the phenotypic and the genotypic level to characterize the evolutionary process followed by the virus in each case and the amount of convergent genetic changes attained. Finally, we also investigated the influence of the pre-existent genetic diversity on adaptation to high temperature. The main conclusions that arise from our results are: i under periodically changing temperature conditions, evolution of bacteriophage Qβ is driven by the most stringent selective pressure, ii there is a high degree of evolutionary convergence between replicated populations and also among populations evolved at different temperatures, iii there are mutations specific of a particular condition, and iv adaptation to high temperatures in populations differing in their pre-existent genetic diversity takes place through the selection of a common set of mutations.

  20. Nitrate decreases xanthine oxidoreductase-mediated nitrite reductase activity and attenuates vascular and blood pressure responses to nitrite

    Directory of Open Access Journals (Sweden)

    Célio Damacena-Angelis

    2017-08-01

    Full Text Available Nitrite and nitrate restore deficient endogenous nitric oxide (NO production as they are converted back to NO, and therefore complement the classic enzymatic NO synthesis. Circulating nitrate and nitrite must cross membrane barriers to produce their effects and increased nitrate concentrations may attenuate the nitrite influx into cells, decreasing NO generation from nitrite. Moreover, xanthine oxidoreductase (XOR mediates NO formation from nitrite and nitrate. However, no study has examined whether nitrate attenuates XOR-mediated NO generation from nitrite. We hypothesized that nitrate attenuates the vascular and blood pressure responses to nitrite either by interfering with nitrite influx into vascular tissue, or by competing with nitrite for XOR, thus inhibiting XOR-mediated NO generation. We used two independent vascular function assays in rats (aortic ring preparations and isolated mesenteric arterial bed perfusion to examine the effects of sodium nitrate on the concentration-dependent responses to sodium nitrite. Both assays showed that nitrate attenuated the vascular responses to nitrite. Conversely, the aortic responses to the NO donor DETANONOate were not affected by sodium nitrate. Further confirming these results, we found that nitrate attenuated the acute blood pressure lowering effects of increasing doses of nitrite infused intravenously in freely moving rats. The possibility that nitrate could compete with nitrite and decrease nitrite influx into cells was tested by measuring the accumulation of nitrogen-15-labeled nitrite (15N-nitrite by aortic rings using ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS. Nitrate exerted no effect on aortic accumulation of 15N-nitrite. Next, we used chemiluminescence-based NO detection to examine whether nitrate attenuates XOR-mediated nitrite reductase activity. Nitrate significantly shifted the Michaelis Menten saturation curve to the right, with a 3-fold increase in

  1. Remnant Cholesterol, Low-Density Lipoprotein Cholesterol, and Blood Pressure as Mediators From Obesity to Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Smith, George Davey

    2015-01-01

    RATIONALE: Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. OBJECTIVE: To test the hypothesis that the increased IHD risk because of obesity is mediated through...... variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood...... obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. CONCLUSIONS: The increased IHD risk because...

  2. Altering the selection capabilities of common cloning vectors via restriction enzyme mediated gene disruption

    Science.gov (United States)

    2013-01-01

    Background The cloning of gene sequences forms the basis for many molecular biological studies. One important step in the cloning process is the isolation of bacterial transformants carrying vector DNA. This involves a vector-encoded selectable marker gene, which in most cases, confers resistance to an antibiotic. However, there are a number of circumstances in which a different selectable marker is required or may be preferable. Such situations can include restrictions to host strain choice, two phase cloning experiments and mutagenesis experiments, issues that result in additional unnecessary cloning steps, in which the DNA needs to be subcloned into a vector with a suitable selectable marker. Results We have used restriction enzyme mediated gene disruption to modify the selectable marker gene of a given vector by cloning a different selectable marker gene into the original marker present in that vector. Cloning a new selectable marker into a pre-existing marker was found to change the selection phenotype conferred by that vector, which we were able to demonstrate using multiple commonly used vectors and multiple resistance markers. This methodology was also successfully applied not only to cloning vectors, but also to expression vectors while keeping the expression characteristics of the vector unaltered. Conclusions Changing the selectable marker of a given vector has a number of advantages and applications. This rapid and efficient method could be used for co-expression of recombinant proteins, optimisation of two phase cloning procedures, as well as multiple genetic manipulations within the same host strain without the need to remove a pre-existing selectable marker in a previously genetically modified strain. PMID:23497512

  3. Structural Basis for Receptor-Mediated Selective Autophagy of Aminopeptidase I Aggregates

    Directory of Open Access Journals (Sweden)

    Akinori Yamasaki

    2016-06-01

    Full Text Available Selective autophagy mediates the degradation of various cargoes, including protein aggregates and organelles, thereby contributing to cellular homeostasis. Cargo receptors ensure selectivity by tethering specific cargo to lipidated Atg8 at the isolation membrane. However, little is known about the structural requirements underlying receptor-mediated cargo recognition. Here, we report structural, biochemical, and cell biological analysis of the major selective cargo protein in budding yeast, aminopeptidase I (Ape1, and its complex with the receptor Atg19. The Ape1 propeptide has a trimeric coiled-coil structure, which tethers dodecameric Ape1 bodies together to form large aggregates. Atg19 disassembles the propeptide trimer and forms a 2:1 heterotrimer, which not only blankets the Ape1 aggregates but also regulates their size. These receptor activities may promote elongation of the isolation membrane along the aggregate surface, enabling sequestration of the cargo with high specificity.

  4. Examination of the selective pressures on a live PRRS vaccine virus

    DEFF Research Database (Denmark)

    Storgaard, Torben; Oleksiewicz, M.; Bøtner, Anette

    1999-01-01

    We determined the ORF5 and 7 sequences of 20 pathogenic revertants of a live PRRSV vaccine. The sequence analysis confirmed all 20 isolates to be of vaccine origin. Having established that clonal introduction of American (vaccine) PRRS virus had occurred in Denmark, we could perform analysis...... were tolerated or even selected for. The cDNA sequencing of the 20 vaccine virus revertants identified two single nucleotide mutations located in ORF5 and in ORF6 that we suggest are involved or at least linked to the attenuation of the vaccine virus and to the subsequent reversion to virulence....... of the selective pressure this attenuated virus had experienced during reversion. An analysis of nucleotide mutations showed a similar rate of mutations in the two genes (ORF5 and 7). However, non-synonymous mutations in ORF7 were eliminated by purifying selection. In contrast, non-synonymous mutations in ORF5...

  5. Application of GFAT as a novel selection marker to mediate gene expression.

    Directory of Open Access Journals (Sweden)

    Guogan Wu

    Full Text Available The enzyme glutamine: fructose-6-phosphate aminotransferase (GFAT, also known as glucosamine synthase (GlmS, catalyzes the formation of glucosamine-6-phosphate from fructose-6-phosphate and is the first and rate-limiting enzyme of the hexosamine biosynthetic pathway. For the first time, the GFAT gene was proven to possess a function as an effective selection marker for genetically modified (GM microorganisms. This was shown by construction and analysis of two GFAT deficient strains, E. coli ΔglmS and S. pombe Δgfa1, and the ability of the GFAT encoding gene to mediate plasmid selection. The gfa1 gene of the fission yeast Schizosaccharomyces pombe was deleted by KanMX6-mediated gene disruption and the Cre-loxP marker removal system, and the glmS gene of Escherichia coli was deleted by using λ-Red mediated recombinase system. Both E. coli ΔglmS and S. pombe Δgfa1 could not grow normally in the media without addition of glucosamine. However, the deficiency was complemented by transforming the plasmids that expressed GFAT genes. The xylanase encoding gene, xynA2 from Thermomyces lanuginosus was successfully expressed and secreted by using GFAT as selection marker in S. pombe. Optimal glucosamine concentration for E. coli ΔglmS and S. pombe Δgfa1 growth was determined respectively. These findings provide an effective technique for the construction of GM bacteria without an antibiotic resistant marker, and the construction of GM yeasts to be applied to complex media.

  6. Pipe leak diagnostic using high frequency piezoelectric pressure sensor and automatic selection of intrinsic mode function

    Science.gov (United States)

    Yusop, Hanafi M.; Ghazali, M. F.; Yusof, M. F. M.; Remli, M. A. Pi; Kamarulzaman, M. H.

    2017-10-01

    In a recent study, the analysis of pressure transient signals could be seen as an accurate and low-cost method for leak and feature detection in water distribution systems. Transient phenomena occurs due to sudden changes in the fluid’s propagation in pipelines system caused by rapid pressure and flow fluctuation due to events such as closing and opening valves rapidly or through pump failure. In this paper, the feasibility of the Hilbert-Huang transform (HHT) method/technique in analysing the pressure transient signals in presented and discussed. HHT is a way to decompose a signal into intrinsic mode functions (IMF). However, the advantage of HHT is its difficulty in selecting the suitable IMF for the next data postprocessing method which is Hilbert Transform (HT). This paper reveals that utilizing the application of an integrated kurtosis-based algorithm for a z-filter technique (I-Kaz) to kurtosis ratio (I-Kaz-Kurtosis) allows/contributes to/leads to automatic selection of the IMF that should be used. This technique is demonstrated on a 57.90-meter medium high-density polyethylene (MDPE) pipe installed with a single artificial leak. The analysis results using the I-Kaz-kurtosis ratio revealed/confirmed that the method can be used as an automatic selection of the IMF although the noise level ratio of the signal is low. Therefore, the I-Kaz-kurtosis ratio method is recommended as a means to implement an automatic selection technique of the IMF for HHT analysis.

  7. [Selection of occlusal scheme on the basis of pressure distribution on supporting structures under complete dentures].

    Science.gov (United States)

    Nagao, Kan; Kawano, Fumiaki; Ichikawa, Tetsuo

    2004-12-01

    In case of making complete dentures, we have to consider not only denture stability but also the restoration of aesthetics and function such as mastication and speech. However these are contradictory theoretically from the point of view of denture stability, and it is very difficult to satisfy both requirements in the case of a patient who has poor upper and lower alveolar ridges. We investigated the effect of artificial posterior teeth form and occlusal scheme on the distribution of pressure on supporting structures under complete dentures during mastication with upper and lower edentulous simulators. In this report, a guideline for the selection of occlusal scheme for complete dentures, based on our previous investigations, is described. The occlusal scheme remarkably affected the distribution of pressure under simulated complete dentures, as shown by comparing the distribution of pressure using two different occlusal schemes:fully balanced occlusion and lingualized occlusion. However other factors such as posterior teeth form and position affect the distribution of pressure as well, and are related to each other. Therefore, not only occlusal scheme but also posterior artificial teeth form has to be considered, and the form of posterior teeth should be carefully and comprehensively decided when making complete dentures.

  8. Dispersal and selection mediate hybridization between a native and invasive species

    Science.gov (United States)

    Kovach, Ryan P.; Muhlfeld, Clint C.; Boyer, Matthew C.; Lowe, Winsor H.; Allendorf, Fred W.; Luikart, Gordon

    2015-01-01

    Hybridization between native and non-native species has serious biological consequences, but our understanding of how dispersal and selection interact to influence invasive hybridization is limited. Here, we document the spread of genetic introgression between a native (Oncorhynchus clarkii) and invasive (Oncorhynchus mykiss) trout, and identify the mechanisms influencing genetic admixture. In two populations inhabiting contrasting environments, non-native admixture increased rapidly from 1984 to 2007 and was driven by surprisingly consistent processes. Individual admixture was related to two phenotypic traits associated with fitness: size at spawning and age of juvenile emigration. Fish with higher non-native admixture were larger and tended to emigrate at a younger age—relationships that are expected to confer fitness advantages to hybrid individuals. However, strong selection against non-native admixture was evident across streams and cohorts (mean selection coefficient against genotypes with non-native alleles (s) ¼ 0.60; s.e. ¼ 0.10). Nevertheless, hybridization was promoted in both streams by the continuous immigration of individuals with high levels of non-native admixture from other hybrid source populations. Thus, antagonistic relationships between dispersal and selection are mediating invasive hybridization between these fish, emphasizing that data on dispersal and natural selection are needed to fully understand the dynamics of introgression between native and non-native species. .

  9. Social variables exert selective pressures in the evolution and form of primate mimetic musculature.

    Science.gov (United States)

    Burrows, Anne M; Li, Ly; Waller, Bridget M; Micheletta, Jerome

    2016-04-01

    Mammals use their faces in social interactions more so than any other vertebrates. Primates are an extreme among most mammals in their complex, direct, lifelong social interactions and their frequent use of facial displays is a means of proximate visual communication with conspecifics. The available repertoire of facial displays is primarily controlled by mimetic musculature, the muscles that move the face. The form of these muscles is, in turn, limited by and influenced by phylogenetic inertia but here we use examples, both morphological and physiological, to illustrate the influence that social variables may exert on the evolution and form of mimetic musculature among primates. Ecomorphology is concerned with the adaptive responses of morphology to various ecological variables such as diet, foliage density, predation pressures, and time of day activity. We present evidence that social variables also exert selective pressures on morphology, specifically using mimetic muscles among primates as an example. Social variables include group size, dominance 'style', and mating systems. We present two case studies to illustrate the potential influence of social behavior on adaptive morphology of mimetic musculature in primates: (1) gross morphology of the mimetic muscles around the external ear in closely related species of macaque (Macaca mulatta and Macaca nigra) characterized by varying dominance styles and (2) comparative physiology of the orbicularis oris muscle among select ape species. This muscle is used in both facial displays/expressions and in vocalizations/human speech. We present qualitative observations of myosin fiber-type distribution in this muscle of siamang (Symphalangus syndactylus), chimpanzee (Pan troglodytes), and human to demonstrate the potential influence of visual and auditory communication on muscle physiology. In sum, ecomorphologists should be aware of social selective pressures as well as ecological ones, and that observed morphology might

  10. Evolutionary allometry reveals a shift in selection pressure on male horn size.

    Science.gov (United States)

    Tidière, M; Lemaître, J-F; Pélabon, C; Gimenez, O; Gaillard, J-M

    2017-10-01

    How selection pressures acting within species interact with developmental constraints to shape macro-evolutionary patterns of species divergence is still poorly understood. In particular, whether or not sexual selection affects evolutionary allometry, the increase in trait size with body size across species, of secondary sexual characters, remains largely unknown. In this context, bovid horn size is an especially relevant trait to study because horns are present in both sexes, but the intensity of sexual selection acting on them is expected to vary both among species and between sexes. Using a unique data set of sex-specific horn size and body mass including 91 species of bovids, we compared the evolutionary allometry between horn size and body mass between sexes while accounting for both the intensity of sexual selection and phylogenetic relationship among species. We found a nonlinear evolutionary allometry where the allometric slope decreased with increasing species body mass. This pattern, much more pronounced in males than in females, suggests either that horn size is limited by some constraints in the largest bovids or is no longer the direct target of sexual selection in very large species. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  11. ROS accumulation by PEITC selectively kills ovarian cancer cells via UPR-mediated apoptosis

    Directory of Open Access Journals (Sweden)

    Yoon-hee eHong

    2015-07-01

    Full Text Available Unfolded protein response (UPR is crucial for both survival and death of mammalian cells, which is regulated by reactive oxygen species (ROS and nutrient depletion. In this study, we demonstrated the effect of ROS-accumulation, induced by β-phenethyl isothiocyanate (PEITC, on UPR mediated apoptosis in ovarian cancer cells. We used ovarian cancer cell lines, PA-1 and SKOV-3, with different p53 status (wild- and null- type, respectively. PEITC caused increased ROS-accumulation and inhibited proliferation selectively in ovarian cancer cells, and glutathione (GSH depletion in SKOV-3. However, PEITC did not cause any effect in normal ovarian epithelial cells and peripheral blood mononuclear cells. After 48 h of PEITC treatment (5 µM, apoptotic cell death was shown to increase significantly in the ovarian cancer cells and not in the normal cells. The key regulator of UPR-mediated apoptosis, CHOP/GADD153 and ER resident chaperone BiP/GRP78 were parallely up-regulated with activation of two major sensors of the UPR (PERK and ATF-6 in PA-1; PERK, and IRE1α in SKOV-3 in response to ROS accumulation induced by PEITC (5 µM. ROS scavenger, N-acetyl-cysteine (NAC, attenuated the effect of PEITC on UPR signatures (P-PERK, IRE1α, CHOP/GADD153, and BiP/GRP78, suggesting the involvement of ROS in UPR-mediated apoptosis. Altogether, PEITC induces UPR-mediated apoptosis in ovarian cancer cells via accumulation of ROS in a cancer-specific manner.

  12. Hitting times of local and global optima in genetic algorithms with very high selection pressure

    Directory of Open Access Journals (Sweden)

    Eremeev Anton V.

    2017-01-01

    Full Text Available The paper is devoted to upper bounds on the expected first hitting times of the sets of local or global optima for non-elitist genetic algorithms with very high selection pressure. The results of this paper extend the range of situations where the upper bounds on the expected runtime are known for genetic algorithms and apply, in particular, to the Canonical Genetic Algorithm. The obtained bounds do not require the probability of fitness-decreasing mutation to be bounded by a constant which is less than one.

  13. MEDIATING ROLE OF EMPLOYEE MOTIVATION IN RELATIONSHIP TO POST-SELECTION HRM PRACTICES AND ORGANIZATIONAL PERFORMANCE

    Directory of Open Access Journals (Sweden)

    Aftab Tariq Dar

    2014-07-01

    Full Text Available The purpose of this cross-sectional study was to explore the meditating role of employee motivation in the relationship between post-selection Human Resource Management (HRM practices and perceived performance of Islamic Banks operating in Pakistan. This study was based on primary data collected from 200-employees of different Islamic banks in Pakistan by distributing structured and reliable questionnaires. The demographic profile of respondents was diversified in terms of their grade, age, experience and education. Results of correlation analysis revealed that training & development(r = .829, performance evaluation system(r = .752, career development system(r = .666, extrinsic rewards(r = .921, intrinsic rewards (r = .852 and employee motivation(r =.722 have strong positive association with perceived performance of Islamic banks in Pakistan. Results of hierarchical regression analysis supported that post-selection HRM practices have positive impact on perceived organizational performance and employee motivation acts as mediator in the relationship between post-selection HRM practices and perceived organizational performance. Proper implementation of post-selection HRM practices makes employee motivated that resulted in improved organizational performance. Management of Islamic banks desiring optimum performance should pay special attention to need-based training programs, merit-based performance appraisal system, development of progressive career paths, performance-based extrinsic and intrinsic rewards management. While making HRM policies, employee motivation should be given paramount importance as the results of contemporary studies supported that it is the major contributing factor of higher organizational performance.

  14. The physical environment mediates male harm and its effect on selection in females.

    Science.gov (United States)

    Yun, Li; Chen, Patrick J; Singh, Amardeep; Agrawal, Aneil F; Rundle, Howard D

    2017-07-12

    Recent experiments indicate that male preferential harassment of high-quality females reduces the variance in female fitness, thereby weakening natural selection through females and hampering adaptation and purging. We propose that this phenomenon, which results from a combination of male choice and male-induced harm, should be mediated by the physical environment in which intersexual interactions occur. Using Drosophila melanogaster , we examined intersexual interactions in small and simple (standard fly vials) versus slightly more realistic (small cages with spatial structure) environments. We show that in these more realistic environments, sexual interactions are less frequent, are no longer biased towards high-quality females, and that overall male harm is reduced. Next, we examine the selective advantage of high- over low-quality females while manipulating the opportunity for male choice. Male choice weakens the viability advantage of high-quality females in the simple environment, consistent with previous work, but strengthens selection on females in the more realistic environment. Laboratory studies in simple environments have strongly shaped our understanding of sexual conflict but may provide biased insight. Our results suggest that the physical environment plays a key role in the evolutionary consequences of sexual interactions and ultimately the alignment of natural and sexual selection. © 2017 The Author(s).

  15. Stress, Time Pressure, Strategy Selection and Math Anxiety in Mathematics: A Review of the Literature

    Directory of Open Access Journals (Sweden)

    Sara Caviola

    2017-09-01

    Full Text Available We review how stress induction, time pressure manipulations and math anxiety can interfere with or modulate selection of problem-solving strategies (henceforth “strategy selection” in arithmetical tasks. Nineteen relevant articles were identified, which contain references to strategy selection and time limit (or time manipulations, with some also discussing emotional aspects in mathematical outcomes. Few of these take cognitive processes such as working memory or executive functions into consideration. We conclude that due to the sparsity of available literature our questions can only be partially answered and currently there is not much evidence of clear associations. We identify major gaps in knowledge and raise a series of open questions to guide further research.

  16. Perceived social pressure not to experience negative emotion is linked to selective attention for negative information.

    Science.gov (United States)

    Bastian, Brock; Pe, Madeline Lee; Kuppens, Peter

    2017-02-01

    Social norms and values may be important predictors of how people engage with and regulate their negative emotional experiences. Previous research has shown that social expectancies (the perceived social pressure not to feel negative emotion (NE)) exacerbate feelings of sadness. In the current research, we examined whether social expectancies may be linked to how people process emotional information. Using a modified classical flanker task involving emotional rather than non-emotional stimuli, we found that, for those who experienced low levels of NE, social expectancies were linked to the selective avoidance of negative emotional information. Those who experienced high levels of NE did not show a selective avoidance of negative emotional information. The findings suggest that, for people who experience many NEs, social expectancies may lead to discrepancies between how they think they ought to feel and the kind of emotional information they pay attention to.

  17. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction....... From the perspective of mediatization research, the most important effect of the media stems from their embeddedness in culture and society....

  18. Age-related weakening of baroreflex-mediated sympathetic activity in spontaneously hypertensive rats in response to blood pressure reduction.

    Science.gov (United States)

    Prados, P; Santa, T; Fukushima, T; Homma, H; Kasai, C; Martin, M A; del Castillo, B; Imai, K

    1998-09-01

    Nicardipine, a dihydropyridine type calcium channel blocker, was infused into 4-, 6-, and 23-wk-old spontaneously hypertensive (SH) and age-matched normotensive Wistar-Kyoto (WKY) rats (under sodium thiobutabarbital anesthesia and ventilation, n = 4) through the left femoral vein, resulting in the reduction of blood pressure. In each rat, mean arterial blood pressure, heart rate, and the concentration of plasma catecholamines (CAs), norepinephrine (NE), and epinephrine (E) were concomitantly determined, and the correlations between these three variables were studied. During the infusion of nicardipine, the plasma concentration of CAs was measured with an automatic detection system in blood samples collected from the right femoral artery of each rat. The reduction in blood pressure induced by nicardipine brought about an increase in plasma CA levels. The blood pressure correlated well with the logarithm of plasma NE or E concentration according to the formula Y= -alpha log (X) + m (Y, blood pressure; X, concentration of plasma NE or E; a, slope; and m, intercept). The slopes (as) of 6-wk-old and 23-wk-old SH rats were significantly greater than those of aged-matched WKY rats, meaning that the increment in plasma CAs in response to a decrease in blood pressure was smaller in SH than in WKY rats of similar ages. However, no significant differences were found between the as of 4-wk-old SH and WKY rats. We conclude that the increment in the baroreflex-mediated sympathetic activity in response to a drop in blood pressure induced by nicardipine is similar or greater in prehypertensive SH than in normotensive WKY 4-wk-old rats, while the increment becomes smaller in SH rats with the onset of hypertension (6-wk-old rats), and is much less in fully hypertensive adult (23-wk-old) SH rats than in age-matched WKY rats. On the basis of these findings and previous data obtained by neurography, we conclude that plasma CAs can be used to evaluate baroreflex-mediated sympathetic

  19. Orbital-selective insulator-metal transition in V2 O3 under external pressure

    Science.gov (United States)

    Laad, M. S.; Craco, L.; Müller-Hartmann, E.

    2006-01-01

    We present a detailed account of the physics of vanadium sesquioxide (V2O3) , a benchmark system for studying correlation-induced metal-insulator transition(s). Based on a detailed perusal of a wide range of experimental data, we stress the importance of multiorbital Coulomb interactions in concert with first-principles local-density approximation (LDA) band structure for a consistent understanding of the insulator-metal (IM) transition under pressure. Using LDA+DMFT (dynamical mean-field theory), we show how the IM transition is of the orbital selective type, driven by large changes in dynamical spectral weight in response to small changes in trigonal field splitting under pressure. Very good quantitative agreement with (i) the switch of orbital occupation and (ii) S=1 at each V3+ site across the IM transition, and (iii) carrier effective mass in the paramagnetic phase, is obtained. Finally, using the LDA+DMFT solution, we have estimated screening-induced renormalization of the local, multiorbital Coulomb interactions. Computation of the one-particle spectral function using these screened values is shown to be in excellent quantitative agreement with very recent experimental (photoemission and x-ray-absorption spectroscopy) results. These findings provide strong support for an orbital-selective Mott transition in paramagnetic V2O3 .

  20. Beyond EICA: understanding post-establishment evolution requires a broader evaluation of potential selection pressures

    Directory of Open Access Journals (Sweden)

    Joshua Atwood

    2011-10-01

    Full Text Available Research on post-establishment evolution in nonnative plant populations has focused almost exclusively on testing the Evolution of Increased Competitive Ability (EICA hypothesis, which posits that the lack of specialized herbivores in the invaded range drives evolution in nonnative plant populations. Fifteen years of conflicting EICA test results suggest that selection pressures other than specialized herbivory are important in driving post-establishment evolution in invasive species. Alternative hypotheses, such as the Evolution of Reduced Competitive Ability (ERCA hypothesis, have been proposed but have received little attention or testing. We argue that the lack of consensus across studies that test EICA may be due in part to the lack of consistent definitions and varying experimental design parameters, and that future research in this field would benefit from new methodological considerations. We examined previous work evaluating post-establishment evolution and evaluated the range of study systems and design parameters used in testing the EICA hypothesis. Our goal was to identify where different uses of ecological terms and different study parameters have hindered consensus and to suggest a path forward to move beyond EICA in post-establishment evolution studies. We incorporated these methods into a design framework that will increase data harmony across future studies and will facilitate examinations of any potential selection pressure driving evolution in the invaded range.

  1. Inflammatory Mediators Associated With Pressure Ulcer Development in Individuals With Pneumonia After Traumatic Spinal Cord Injury: A Pilot Study.

    Science.gov (United States)

    Krishnan, Shilpa; Vodovotz, Yoram; Karg, Patricia E; Constantine, Gregory; Sowa, Gwendolyn A; Constantine, Florica J; Brienza, David M

    2017-09-01

    To identify the inflammatory mediators around the time of pneumonia onset associated with concurrent or later onset of pressure ulcers (PUs). Retrospective. Acute hospitalization and inpatient rehabilitation unit of a university medical center. Individuals (N=86) with traumatic spinal cord injury (SCI) were included in the initial analyses. Fifteen of the 86 developed pneumonia and had inflammatory mediator data available. Of these 15, 7 developed PUs and 8 did not. Not applicable. Twenty-three inflammatory mediators in plasma and urine were assayed. The differences in concentrations of plasma and urine inflammatory mediators between the closest time point before and after the diagnosis of pneumonia were calculated. Initial chi-square analysis revealed a significant (P=.02) association between pneumonia and PUs. Individuals with SCI and diagnosed pneumonia had nearly double the risk for developing PUs compared with those with no pneumonia. In individuals with pneumonia, Mann-Whitney U exact tests suggested an association (Ppneumonia. These findings suggest that a relatively small increase in plasma TNF-α, and decreases in urine TNF-α, GM-CSF, and IL-15 from just before to just after the diagnosis of pneumonia could be markers for an increased risk of PUs in individuals with pneumonia after traumatic SCI. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  2. Plasma-mediated vascular dysfunction in the reduced uterine perfusion pressure model of preeclampsia: a microvascular characterization.

    LENUS (Irish Health Repository)

    Walsh, Sarah K

    2012-01-31

    Preeclampsia is associated with widespread maternal vascular dysfunction, which is thought to be mediated by circulating factor(s). The aim of the study was to characterize vascular function in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia and to investigate the role of plasma factors in mediating any observed changes in vascular reactivity. Mean arterial blood pressure and vascular function were measured in RUPP and control rats. Mesenteric vessels from both virgin and pregnant rats were exposed for 1 hour or overnight to plasma from both RUPP and control rats and their vascular function assessed. RUPP rats were characterized by severe hypertension, restricted fetal growth, and reduced placental weight (P<0.001). Vasorelaxation was impaired in resistance vessels from RUPP compared with control rats (acetylcholine: R(max) 70+\\/-3 versus 92+\\/-1 [NP] and 93+\\/-3% [sham], P<0.01; bradykinin: 40+\\/-2 versus 62+\\/-2 [NP] and 59+\\/-4% [sham], P<0.001). Incubation of vessels from pregnant (but not virgin) animals with RUPP plasma overnight resulted in an attenuation of vasorelaxant responses (acetylcholine: 63+\\/-7 versus 86+\\/-2%, P<0.05; bradykinin: 35+\\/-5 versus 55+\\/-6%, P<0.001). The residual relaxant response in RUPP plasma-treated vessels was not further attenuated after treatment with N(omega)-nitro-l-arginine methyl ester (acetylcholine: 57+\\/-7 versus 63+\\/-7%, ns; bradykinin: 37+\\/-5 versus 35+\\/-5%, ns). The RUPP rat model is characterized by an impaired response to vasodilators which may be attributable to one or more circulating factors. This plasma-mediated endothelial dysfunction appears to be a pregnancy-dependent effect. Furthermore, nitric oxide-mediated vasorelaxation appears to be absent in RUPP plasma-treated vessels.

  3. Quantitating the specificity and selectivity of Gcn5-mediated acetylation of histone H3.

    Directory of Open Access Journals (Sweden)

    Yin-Ming Kuo

    Full Text Available Lysine acetyltransferases (KATs play a unique role in regulating gene transcription as well as maintaining the epigenetic state of the cell. KATs such as Gcn5 and p300/CBP can modify multiple residues on a single histone; however, order and specificity of acetylation can be altered by factors such as histone chaperones, subunit proteins or external stimulus. While the importance of acetylation is well documented, it has been difficult to quantitatively measure the specificity and selectivity of acetylation at different residues within a histone. In this paper, we demonstrate a label-free quantitative high throughput mass spectrometry-based assay capable of quantitatively monitoring all known acetylation sites of H3 simultaneously. Using this assay, we are able to analyze the steady-state enzyme kinetics of Gcn5, an evolutionarily conserved KAT. In doing so, we measured Gcn5-mediated acetylation at six residues (K14>K9 ≈ K23> K18> K27 ≈ K36 and the catalytic efficiency (k(cat/K(m for K9, K14, K18, and K23 as well as the nonenzymatic acetylation rate. We observed selectivity differences of up to -4 kcal/mol between K14 and K18, the highest and lowest measurable k(cat/K(m. These data provide a first look at quantitating the specificity and selectivity of multiple lysines on a single substrate (H3 by Gcn5.

  4. Social determinants and the classification of disease: descriptive epidemiology of selected socially mediated disease constellations.

    Science.gov (United States)

    Levine, Robert S; Kilbourne, Barbara A; Rust, George S; Langston, Michael A; Husaini, Baqar A; Gittner, Lisaann S; Sanderson, Maureen; Hennekens, Charles H

    2014-01-01

    Most major diseases have important social determinants. In this context, classification of disease based on etiologic or anatomic criteria may be neither mutually exclusive nor optimal. Units of analysis comprised large metropolitan central and fringe metropolitan counties with reliable mortality rates--(n = 416). Participants included infants and adults ages 25 to 64 years with selected causes of death (1999 to 2006). Exposures included that residential segregation and race-specific social deprivation variables. Main outcome measures were obtained via principal components analyses with an orthogonal rotation to identify a common factor. To discern whether the common factor was socially mediated, negative binomial multiple regression models were developed for which the dependent variable was the common factor. Results showed that infant deaths, mortality from assault, and malignant neoplasm of the trachea, bronchus and lung formed a common factor for race-gender groups (black/white and men/women). Regression analyses showed statistically significant, positive associations between low socio-economic status for all race-gender groups and this common factor. Between 1999 and 2006, deaths classified as "assault" and "lung cancer", as well as "infant mortality" formed a socially mediated factor detectable in population but not individual data. Despite limitations related to death certificate data, the results contribute important information to the formulation of several hypotheses: (a) disease classifications based on anatomic or etiologic criteria fail to account for social determinants; (b) social forces produce demographically and possibly geographically distinct population-based disease constellations; and (c) the individual components of population-based disease constellations (e.g., lung cancer) are phenotypically comparable from one population to another but genotypically different, in part, because of socially mediated epigenetic variations. Additional research

  5. Social determinants and the classification of disease: descriptive epidemiology of selected socially mediated disease constellations.

    Directory of Open Access Journals (Sweden)

    Robert S Levine

    Full Text Available Most major diseases have important social determinants. In this context, classification of disease based on etiologic or anatomic criteria may be neither mutually exclusive nor optimal.Units of analysis comprised large metropolitan central and fringe metropolitan counties with reliable mortality rates--(n = 416. Participants included infants and adults ages 25 to 64 years with selected causes of death (1999 to 2006. Exposures included that residential segregation and race-specific social deprivation variables. Main outcome measures were obtained via principal components analyses with an orthogonal rotation to identify a common factor. To discern whether the common factor was socially mediated, negative binomial multiple regression models were developed for which the dependent variable was the common factor. Results showed that infant deaths, mortality from assault, and malignant neoplasm of the trachea, bronchus and lung formed a common factor for race-gender groups (black/white and men/women. Regression analyses showed statistically significant, positive associations between low socio-economic status for all race-gender groups and this common factor.Between 1999 and 2006, deaths classified as "assault" and "lung cancer", as well as "infant mortality" formed a socially mediated factor detectable in population but not individual data. Despite limitations related to death certificate data, the results contribute important information to the formulation of several hypotheses: (a disease classifications based on anatomic or etiologic criteria fail to account for social determinants; (b social forces produce demographically and possibly geographically distinct population-based disease constellations; and (c the individual components of population-based disease constellations (e.g., lung cancer are phenotypically comparable from one population to another but genotypically different, in part, because of socially mediated epigenetic variations

  6. Zirconia enrichment in zircon sand by selective fungus-mediated bioleaching of silica.

    Science.gov (United States)

    Bansal, Vipul; Syed, Asad; Bhargava, Suresh K; Ahmad, Absar; Sastry, Murali

    2007-04-24

    One of the important routes for the production of zirconia is by chemical treatment and removal of silica from zircon sand (ZrSixOy). We present here a completely green chemistry approach toward enrichment of zirconia in zircon sand; this is based on the reaction of the fungus Fusarium oxysporum with zircon sand by a process of selective extracellular bioleaching of silica nanoparticles. Since this reaction does not result in zirconia being simultaneously leached out from the sand, there is a consequent enrichment of the zirconia component in zircon sand. We believe that fungal enzymes specifically hydrolyze the silicates present in the sand to form silicic acid, which on condensation by certain other fungal enzymes results in room-temperature synthesis of silica nanoparticles. This fungus-mediated twofold approach might have vast commercial implications in low-cost, ecofriendly, room-temperature syntheses of technologically important oxide nanomaterials from potentially cheap naturally available raw materials like zircon sand.

  7. Genomic Signatures of Selective Pressures and Introgression from Archaic Hominins at Human Innate Immunity Genes.

    Science.gov (United States)

    Deschamps, Matthieu; Laval, Guillaume; Fagny, Maud; Itan, Yuval; Abel, Laurent; Casanova, Jean-Laurent; Patin, Etienne; Quintana-Murci, Lluis

    2016-01-07

    Human genes governing innate immunity provide a valuable tool for the study of the selective pressure imposed by microorganisms on host genomes. A comprehensive, genome-wide study of how selective constraints and adaptations have driven the evolution of innate immunity genes is missing. Using full-genome sequence variation from the 1000 Genomes Project, we first show that innate immunity genes have globally evolved under stronger purifying selection than the remainder of protein-coding genes. We identify a gene set under the strongest selective constraints, mutations in which are likely to predispose individuals to life-threatening disease, as illustrated by STAT1 and TRAF3. We then evaluate the occurrence of local adaptation and detect 57 high-scoring signals of positive selection at innate immunity genes, variation in which has been associated with susceptibility to common infectious or autoimmune diseases. Furthermore, we show that most adaptations targeting coding variation have occurred in the last 6,000-13,000 years, the period at which populations shifted from hunting and gathering to farming. Finally, we show that innate immunity genes present higher Neandertal introgression than the remainder of the coding genome. Notably, among the genes presenting the highest Neandertal ancestry, we find the TLR6-TLR1-TLR10 cluster, which also contains functional adaptive variation in Europeans. This study identifies highly constrained genes that fulfill essential, non-redundant functions in host survival and reveals others that are more permissive to change-containing variation acquired from archaic hominins or adaptive variants in specific populations-improving our understanding of the relative biological importance of innate immunity pathways in natural conditions. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  8. Nature and intensity of selection pressure on CRISPR-associated genes.

    Science.gov (United States)

    Takeuchi, Nobuto; Wolf, Yuri I; Makarova, Kira S; Koonin, Eugene V

    2012-03-01

    The recently discovered CRISPR-Cas adaptive immune system is present in almost all archaea and many bacteria. It consists of cassettes of CRISPR repeats that incorporate spacers homologous to fragments of viral or plasmid genomes that are employed as guide RNAs in the immune response, along with numerous CRISPR-associated (cas) genes that encode proteins possessing diverse, only partially characterized activities required for the action of the system. Here, we investigate the evolution of the cas genes and show that they evolve under purifying selection that is typically much weaker than the median strength of purifying selection affecting genes in the respective genomes. The exceptions are the cas1 and cas2 genes that typically evolve at levels of purifying selection close to the genomic median. Thus, although these genes are implicated in the acquisition of spacers from alien genomes, they do not appear to be directly involved in an arms race between bacterial and archaeal hosts and infectious agents. These genes might possess functions distinct from and additional to their role in the CRISPR-Cas-mediated immune response. Taken together with evidence of the frequent horizontal transfer of cas genes reported previously and with the wide-spread microscale recombination within these genes detected in this work, these findings reveal the highly dynamic evolution of cas genes. This conclusion is in line with the involvement of CRISPR-Cas in antiviral immunity that is likely to entail a coevolutionary arms race with rapidly evolving viruses. However, we failed to detect evidence of strong positive selection in any of the cas genes.

  9. A lover or a fighter? Opposing sexual selection pressures on men's vocal pitch and facial hair.

    Science.gov (United States)

    Saxton, Tamsin K; Mackey, Lauren L; McCarty, Kristofor; Neave, Nick

    2016-01-01

    The traditional assumption within the research literature on human sexually dimorphic traits has been that many sex differences have arisen from intersexual selection. More recently, however, there has been a shift toward the idea that many male features, including male lower-pitched voices and male beard growth, might have arisen predominantly through intrasexual selection: that is, to serve the purpose of male-male competition instead of mate attraction. In this study, using a unique set of video stimuli, we measured people's perceptions of the dominance and attractiveness of men who differ both in terms of voice pitch (4 levels from lower to higher pitched) and beard growth (4 levels from clean shaven to a month's hair growth). We found a nonlinear relationship between lower pitch and increased attractiveness; men's vocal attractiveness peaked at around 96 Hz. Beard growth had equivocal effects on attractiveness judgments. In contrast, perceptions of men's dominance simply increased with increasing masculinity (i.e., with lower-pitched voices and greater beard growth). Together, these results suggest that the optimal level of physical masculinity might differ depending on whether the outcome is social dominance or mate attraction. These dual selection pressures might maintain some of the documented variability in male physical and behavioral masculinity that we see today.

  10. Extracellular-matrix-mediated osmotic pressure drives Vibrio cholerae biofilm expansion and cheater exclusion.

    Science.gov (United States)

    Yan, Jing; Nadell, Carey D; Stone, Howard A; Wingreen, Ned S; Bassler, Bonnie L

    2017-08-23

    Biofilms, surface-attached communities of bacteria encased in an extracellular matrix, are a major mode of bacterial life. How the material properties of the matrix contribute to biofilm growth and robustness is largely unexplored, in particular in response to environmental perturbations such as changes in osmotic pressure. Here, using Vibrio cholerae as our model organism, we show that during active cell growth, matrix production enables biofilm-dwelling bacterial cells to establish an osmotic pressure difference between the biofilm and the external environment. This pressure difference promotes biofilm expansion on nutritious surfaces by physically swelling the colony, which enhances nutrient uptake, and enables matrix-producing cells to outcompete non-matrix-producing cheaters via physical exclusion. Osmotic pressure together with crosslinking of the matrix also controls the growth of submerged biofilms and their susceptibility to invasion by planktonic cells. As the basic physicochemical principles of matrix crosslinking and osmotic swelling are universal, our findings may have implications for other biofilm-forming bacterial species.Most bacteria live in biofilms, surface-attached communities encased in an extracellular matrix. Here, Yan et al. show that matrix production in Vibrio cholerae increases the osmotic pressure within the biofilm, promoting biofilm expansion and physical exclusion of non-matrix producing cheaters.

  11. The relationship between PMI (manA) gene expression and optimal selection pressure in Indica rice transformation.

    Science.gov (United States)

    Gui, Huaping; Li, Xia; Liu, Yubo; Han, Kai; Li, Xianggan

    2014-07-01

    An efficient mannose selection system was established for transformation of Indica cultivar IR58025B . Different selection pressures were required to achieve optimum transformation frequency for different PMI selectable marker cassettes. This study was conducted to establish an efficient transformation system for Indica rice, cultivar IR58025B. Four combinations of two promoters, rice Actin 1 and maize Ubiquitin 1, and two manA genes, native gene from E. coli (PMI-01) and synthetic maize codon-optimized gene (PMI-09) were compared under various concentrations of mannose. Different selection pressures were required for different gene cassettes to achieve corresponding optimum transformation frequency (TF). Higher TFs as 54 and 53% were obtained when 5 g/L mannose was used for selection of prActin-PMI-01 cassette and 7.5 g/L mannose used for selection of prActin-PMI-09, respectively. TFs as 67 and 56% were obtained when 7.5 and 15 g/L mannose were used for selection of prUbi-PMI-01 and prUbi-PMI-09, respectively. We conclude that higher TFs can be achieved for different gene cassettes when an optimum selection pressure is applied. By investigating the PMI expression level in transgenic calli and leaves, we found there was a significant positive correlation between the protein expression level and the optimal selection pressure. Higher optimal selection pressure is required for those constructs which confer higher expression of PMI protein. The single copy rate of those transgenic events for prActin-PMI-01 cassette is lower than that for other three cassettes. We speculate some of low copy events with low protein expression levels might not have been able to survive in the mannose selection.

  12. Data from: Evolution of cross-resistance to medical triazoles in Aspergillus fumigatus through selection pressure of environmental fungicides

    NARCIS (Netherlands)

    Zhang, J.; Heuvel, van den Joost; Debets, A.J.M.; Verweij, Paul E.; Melchers, Willem J.G.; Zwaan, B.J.; Schoustra, S.E.

    2017-01-01

    Resistance to medical triazoles in Aspergillus fumigatus is an emerging problem for patients at risk of aspergillus diseases. There are currently two presumed routes for medical triazole-resistance selection: (i) through selection pressure of medical triazoles when treating patients and (ii) through

  13. Evolution of cross-resistance to medical triazoles in Aspergillus fumigatus through selection pressure of environmental fungicides

    NARCIS (Netherlands)

    Zhang, Jianhua; Heuvel, van den Joost; Debets, Fons; Verweij, Paul E.; Melchers, Willem J.G.; Zwaan, Bas J.; Schoustra, Sijmen E.

    2017-01-01

    Resistance to medical triazoles in Aspergillus fumigatus is an emerging problem for patients at risk of aspergillus diseases. There are currently two presumed routes for medical triazole-resistance selection: (i) through selection pressure of medical triazoles when treating patients and (ii)

  14. Evolution of cross-resistance to medical triazoles in Aspergillus fumigatus through selection pressure of environmental fungicides

    NARCIS (Netherlands)

    Zhang, J.; Heuvel, J. van den; Debets, A.J.; Verweij, P.E.; Melchers, W.J.G.; Zwaan, B.J.; Schoustra, S.E.

    2017-01-01

    Resistance to medical triazoles in Aspergillus fumigatus is an emerging problem for patients at risk of aspergillus diseases. There are currently two presumed routes for medical triazole-resistance selection: (i) through selection pressure of medical triazoles when treating patients and (ii) through

  15. Differences in selective pressure on dhps and dhfr drug resistant mutations in western Kenya

    Directory of Open Access Journals (Sweden)

    McCollum Andrea M

    2012-03-01

    pressures on various dhfr and dhps mutants relative to each other based on a theoretical model tailored to P. falciparum. The data indicate that drug selection acted differently on the resistant alleles of dhfr and dhps, as evidenced by fitness differences. Thus a combination drug therapy such as SP, by itself, does not appear to select for "multidrug"-resistant parasites in areas with high recombination rate. Conclusions The complexity of these observations emphasizes the importance of population-based studies to evaluate the effects of strong drug selection on Plasmodium falciparum populations.

  16. Male and female brain evolution is subject to contrasting selection pressures in primates

    Directory of Open Access Journals (Sweden)

    Dunbar Robin IM

    2007-05-01

    Full Text Available Abstract The claim that differences in brain size across primate species has mainly been driven by the demands of sociality (the "social brain" hypothesis is now widely accepted. Some of the evidence to support this comes from the fact that species that live in large social groups have larger brains, and in particular larger neocortices. Lindenfors and colleagues (BMC Biology 5:20 add significantly to our appreciation of this process by showing that there are striking differences between the two sexes in the social mechanisms and brain units involved. Female sociality (which is more affiliative is related most closely to neocortex volume, but male sociality (which is more competitive and combative is more closely related to subcortical units (notably those associated with emotional responses. Thus different brain units have responded to different selection pressures.

  17. BAGE genes generated by juxtacentromeric reshuffling in the Hominidae lineage are under selective pressure.

    Science.gov (United States)

    Ruault, Myriam; Ventura, Mario; Galtier, Nicolas; Brun, Marie-Elisabeth; Archidiacono, Nicoletta; Roizès, Gérard; De Sario, Albertina

    2003-04-01

    In this paper, we show that the BAGE (B melanoma antigen) gene family was generated by chromosome rearrangements that occurred during the evolution of hominoids. An 84-kb DNA fragment derived from the phylogenetic 7q36 region was duplicated in the juxtacentromeric region of either chromosome 13 or chromosome 21. The duplicated region contained a fragment of the MLL3 gene, which, after juxtacentromeric reshuffling, generated the ancestral BAGE gene. Then, this ancestral gene gave rise to several independent genes through successive rounds of inter- and intrachromosome duplications. Comparison of synonymous and nonsynonymous mutations in putative coding regions shows that BAGE genes, but not the BAGE gene fragments, are under selective pressure. Our data strongly suggest that BAGE proteins have a function and that juxtacentromeric regions, whose plasticity is now largely proved, are not a simple junkyard of gene fragments, but may be the birth site of novel genes.

  18. Dynamic escape of pre-existing raltegravir-resistant HIV-1 from raltegravir selection pressure.

    Science.gov (United States)

    Codoñer, Francisco M; Pou, Christian; Thielen, Alexander; García, Federico; Delgado, Rafael; Dalmau, David; Santos, José Ramon; Buzón, Maria José; Martínez-Picado, Javier; Alvarez-Tejado, Miguel; Clotet, Bonaventura; Ruiz, Lidia; Paredes, Roger

    2010-12-01

    Using quantitative deep HIV-1 sequencing in a subject who developed virological failure to deep salvage therapy with raltegravir, we found that most Q148R and N155H mutants detected at the time of virological failure originated from pre-existing minority Q148R and N155H variants through independent evolutionary clusters. Double 148R+N155H mutants were also detected in 1.7% of viruses at virological failure in association with E138K and/or G163R. Our findings illustrate the ability of HIV-1 to escape from suboptimal antiretroviral drug pressure through selection of pre-existing drug-resistant mutants, underscoring the importance of using fully active antiretroviral regimens to treat all HIV-1-infected subjects. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Responses to river inundation pressures control prey selection of riparian beetles.

    Directory of Open Access Journals (Sweden)

    Matt J O'Callaghan

    Full Text Available Riparian habitats are subjected to frequent inundation (flooding and are characterised by food webs that exhibit variability in aquatic/terrestrial subsidies across the ecotone. The strength of this subsidy in active riparian floodplains is thought to underpin local biodiversity. Terrestrial invertebrates dominate the fauna, exhibiting traits that allow exploitation of variable aquatic subsidies while reducing inundation pressures, leading to inter-species micro-spatial positioning. The effect these strategies have on prey selection is not known. This study hypothesised that plasticity in prey choice from either aquatic or terrestrial sources is an important trait linked to inundation tolerance and avoidance.We used hydrological, isotopic and habitat analyses to investigate the diet of riparian Coleoptera in relation to inundation risk and relative spatial positioning in the floodplain. The study examined patch scale and longitudinal changes in utilisation of the aquatic subsidy according to species traits. Prey sourced from terrestrial or emerging/stranded aquatic invertebrates varied in relation to traits for inundation avoidance or tolerance strategies. Traits that favoured rapid dispersal corresponded with highest proportions of aquatic prey, with behavioural traits further predicting uptake. Less able dispersers showed minimal use of aquatic subsidy and switched to a terrestrial diet under moderate inundation pressures. All trait groups showed a seasonal shift in diet towards terrestrial prey in the early spring. Prey selection became exaggerated towards aquatic prey in downstream samples.Our results suggest that partitioning of resources and habitat creates overlapping niches that increase the processing of external subsidies in riparian habitats. By demonstrating functional complexity, this work advances understanding of floodplain ecosystem processes and highlights the importance of hydrological variability. With an increasing interest

  20. Selection pressure on human STR loci and its relevance in repeat expansion disease

    KAUST Repository

    Shimada, Makoto K.

    2016-06-11

    Short Tandem Repeats (STRs) comprise repeats of one to several base pairs. Because of the high mutability due to strand slippage during DNA synthesis, rapid evolutionary change in the number of repeating units directly shapes the range of repeat-number variation according to selection pressure. However, the remaining questions include: Why are STRs causing repeat expansion diseases maintained in the human population; and why are these limited to neurodegenerative diseases? By evaluating the genome-wide selection pressure on STRs using the database we constructed, we identified two different patterns of relationship in repeat-number polymorphisms between DNA and amino-acid sequences, although both patterns are evolutionary consequences of avoiding the formation of harmful long STRs. First, a mixture of degenerate codons is represented in poly-proline (poly-P) repeats. Second, long poly-glutamine (poly-Q) repeats are favored at the protein level; however, at the DNA level, STRs encoding long poly-Qs are frequently divided by synonymous SNPs. Furthermore, significant enrichments of apoptosis and neurodevelopment were biological processes found specifically in genes encoding poly-Qs with repeat polymorphism. This suggests the existence of a specific molecular function for polymorphic and/or long poly-Q stretches. Given that the poly-Qs causing expansion diseases were longer than other poly-Qs, even in healthy subjects, our results indicate that the evolutionary benefits of long and/or polymorphic poly-Q stretches outweigh the risks of long CAG repeats predisposing to pathological hyper-expansions. Molecular pathways in neurodevelopment requiring long and polymorphic poly-Q stretches may provide a clue to understanding why poly-Q expansion diseases are limited to neurodegenerative diseases. © 2016, Springer-Verlag Berlin Heidelberg.

  1. How Work Affects Divorce: The Mediating Role of Financial and Time Pressures

    Science.gov (United States)

    Poortman, Anne-Rigt

    2005-01-01

    This study examines whether the financial and time pressures associated with spouses' working lives play a role in the relation between work and divorce during the first years of marriage. Using retrospective data from the Netherlands, the results show that divorce is more likely when the husband works on average fewer hours and the wife more…

  2. How Work Affects Divorce : The Mediating Role of Financial and Time Pressures

    NARCIS (Netherlands)

    Poortman, Anne-Rigt

    2005-01-01

    This study examines whether the financial and time pressures associatedwith spouses’working lives play a role in the relation between work and divorce during the first years of marriage. Using retrospective data from the Netherlands, the results show that divorce is more likely when the husband

  3. The mediating effects of parental and peer pressure on the migration intentions of graduates in Nanjing

    NARCIS (Netherlands)

    Cui, C.; Geertman, S.C.M.; Hooimeijer, P.

    2016-01-01

    This paper analyses the migration intentions of university graduates using the Theory of Planned Behaviour not just to unravel their intention but also to uncover how subjective perceptions enter the decision-making process. The results suggest that perceived parental and peer pressures have strong

  4. Disagreement in primary study selection between systematic reviews on negative pressure wound therapy

    Directory of Open Access Journals (Sweden)

    Sauerland Stefan

    2008-06-01

    Full Text Available Abstract Background Primary study selection between systematic reviews is inconsistent, and reviews on the same topic may reach different conclusions. Our main objective was to compare systematic reviews on negative pressure wound therapy (NPWT regarding their agreement in primary study selection. Methods This retrospective analysis was conducted within the framework of a systematic review (a full review and a subsequent rapid report on NPWT prepared by the Institute for Quality and Efficiency in Health Care (IQWiG. For the IQWiG review and rapid report, 4 bibliographic databases (MEDLINE, EMBASE, The Cochrane Library, and CINAHL were searched to identify systematic reviews and primary studies on NPWT versus conventional wound therapy in patients with acute or chronic wounds. All databases were searched from inception to December 2006. For the present analysis, reviews on NPWT were classified as eligible systematic reviews if multiple sources were systematically searched and the search strategy was documented. To ensure comparability between reviews, only reviews published in or after December 2004 and only studies published before June 2004 were considered. Eligible reviews were compared in respect of the methodology applied and the selection of primary studies. Results A total of 5 systematic reviews (including the IQWiG review and 16 primary studies were analysed. The reviews included between 4 and 13 primary studies published before June 2004. Two reviews considered only randomised controlled trials (RCTs. Three reviews considered both RCTs and non-RCTs. The overall agreement in study selection between reviews was 96% for RCTs (24 of 25 options and 57% for non-RCTs (12 of 21 options. Due to considerable disagreement in the citation and selection of non-RCTs, we contacted the review authors for clarification (this was not initially planned; all authors or institutions responded. According to published information and the additional

  5. DMPD: Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokinin-1during B-cell development. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14962188 Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokin...ng) (.svg) (.html) (.csml) Show Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokinin...-1during B-cell development. PubmedID 14962188 Title Mechanisms of selection medi

  6. GLUT1-mediated selective tumor targeting with fluorine containing platinum(II) glycoconjugates.

    Science.gov (United States)

    Liu, Ran; Fu, Zheng; Zhao, Meng; Gao, Xiangqian; Li, Hong; Mi, Qian; Liu, Pengxing; Yang, Jinna; Yao, Zhi; Gao, Qingzhi

    2017-06-13

    Increased glycolysis and overexpression of glucose transporters (GLUTs) are physiological characteristics of human malignancies. Based on the so-called Warburg effect, 18flurodeoxyglucose-positron emission tomography (FDG-PET) has successfully developed as clinical modality for the diagnosis and staging of many cancers. To leverage this glucose transporter mediated metabolic disparity between normal and malignant cells, in the current report, we focus on the fluorine substituted series of glucose, mannose and galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-flouromalonato-platinum(II) complexes for a comprehensive evaluation on their selective tumor targeting. Besides highly improved water solubility, these sugar-conjugates presented improved cytotoxicity than oxaliplatin in glucose tranporters (GLUTs) overexpressing cancer cell lines and exhibited no cross-resistance to cisplatin. For the highly water soluble glucose-conjugated complex (5a), two novel in vivo assessments were conducted and the results revealed that 5a was more efficacious at a lower equitoxic dose (70% MTD) than oxaliplatin (100% MTD) in HT29 xenograft model, and it was significantly more potent than oxaliplatin in leukemia-bearing DBA/2 mice as well even at equimolar dose levels (18% vs 90% MTD). GLUT inhibitor mediated cell viability analysis, GLUT1 knockdown cell line-based cytotoxicity evaluation, and platinum accumulation study demonstrated that the cellular uptake of the sugar-conjugates was regulated by GLUT1. The higher intrinsic DNA reactivity of the sugar-conjugates was confirmed by kinetic study of platinum(II)-guanosine adduct formation. The mechanistic origin of the antitumor effect of the fluorine complexes was found to be forming the bifunctional Pt-guanine-guanine (Pt-GG) intrastrand cross-links with DNA. The results provide a rationale for Warburg effect targeted anticancer drug design.

  7. ZK-5: a CO₂-selective zeolite with high working capacity at ambient temperature and pressure.

    Science.gov (United States)

    Liu, Qingling; Pham, Trong; Porosoff, Marc D; Lobo, Raul F

    2012-11-01

    The increased carbon dioxide concentration in the atmosphere caused by combustion of fossil fuels has been a leading contributor to global climate change. The adsorption-driven pressure or vacuum swing (PSA/VSA) processes are promising as affordable means for the capture and separation of CO₂. Herein, an 8-membered-ring zeolite ZK-5 (Framework Type Code: KFI) exchanged with different cations (H⁺, Li⁺, Na⁺, K⁺, Mg²⁺, Ca²⁺) was synthesized as novel CO₂ adsorbent. The samples were characterized by SEM, energy-dispersive X-ray spectroscopy (EDAX), XRD, and gas adsorption (CO₂ and N₂). The Toth adsorption model was used to describe the CO₂ adsorption isotherms, and the isosteric heats of adsorption were calculated. CO₂ capture adsorbent evaluation criteria such as working capacity, regenerability and CO₂/N₂ selectivity were applied to evaluate the zeolite adsorbents for PSA/VSA applications. The in situ FTIR CO₂ adsorption spectra show that physisorption accounts for the largest fraction of the total CO₂ adsorbed. The CO₂ adsorption analysis shows that Mg-ZK-5 is the most promising adsorbent for PSA applications with the highest working capacity (ΔN(CO₂)=2.05 mmol g⁻¹), excellent selectivity (α(CO₂/N₂)=121), and low isosteric heat. Li-, Na- and K-ZK-5 with good working capacity (ΔN(CO₂)=1.55-2.16 mmol g⁻¹) and excellent selectivity (α(CO₂/N₂)=103-128) are promising CO₂ adsorbents for the VSA working region. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Blood pressure in relation to selected anthropometric measurements in senior citizens.

    Science.gov (United States)

    Moni, M A; Rahman, M A; Haque, M A; Islam, M S; Ahmed, K

    2010-04-01

    This cross-sectional study was done to assess the blood pressure of the senior citizens in relation to the anthropometric measurements and indices. It was conducted among the Bangladeshi elderly citizens of selected areas of Dhaka city. Samples were selected by convenient technique. A pre-tested questionnaire and a check list were used for data collection. Data analysis was done by SPSS for Windows. Three areas of Dhaka city namely Nakhal Para, Badda and Mirpur were selected in this study. The study was conducted during January to June 2006. A total of 317 samples were studied. Mean age of the respondents was 67.1 years (+/-6.6 SD). Mean SBP and DBP measured were 126 mm of Hg (+/-20 SD) and 72 mm of Hg (+/-12 SD), respectively. Among them, 33.1% were hypertensive on BP measurement; amongst which 32.4% had both SBP and DBP raised; 55.2% had isolated systolic hypertension and 12.4% had DBP raised. Of them 44.8% were identified finally as hypertensive considering BP measurement and those taking antihypertensive medication. The majority were well nourished and at less health risk in terms of BMI, WC and WHR. There was a tendency of being hypertensive with overweight/obese (p<0.05), high WC (male p<0.05 and female p<0.01) and high WHR (female p<0.001). Percentage of hypertensive was higher among the seniors of the study areas especially among those who were overweight/obese or at health risk by WC/WHR.

  9. Predation determines different selective pressure on pea aphid host races in a complex agricultural mosaic.

    Directory of Open Access Journals (Sweden)

    Adalbert Balog

    Full Text Available Field assessments were conducted to examine the interplay between host plant and predation in complex agricultural mosaic on pea aphid clover and alfalfa races. In one experiment, we examined the relative fitness on clover race (CR and alfalfa race (AR pea aphids on broad bean, red clover and alfalfa alone. But because clover is typically grown in a more complex agricultural mosaic with alfalfa and broad bean, a second experiment was conducted to assess the fitness consequences under predation in a more complex agricultural field setting that also included potential apparent competition with AR pea aphids. In a third experiment we tested for the effect of differential host race density on the fitness of the other host race mediated by a predator effect. CR pea aphids always had fitness losses when on broad bean (had lower fitness on broad bean relative to red clover and fitness benefits when on red clover (higher fitness on red clover relative to broad bean, whether or not in apparent competition with alfalfa race aphids on bean and alfalfa. AR suffered fitness loss on both alfalfa and bean in apparent competition with CR on clover. Therefore we can conclude that the predation rate between host races was highly asymmetrical. The complexity of the agricultural mosaic thus can influence prey selection by predators on different host plants. These may have evolutionary consequences through context dependent fitness benefits on particular host plants.

  10. Relating pressure tuned coupled column ensembles with the solvation parameter model for tunable selectivity in gas chromatography.

    Science.gov (United States)

    Sharif, Khan M; Kulsing, Chadin; Chin, Sung-Tong; Marriott, Philip J

    2016-07-15

    The differential pressure drop of carrier gas by tuning the junction point pressure of a coupled column gas chromatographic system leads to a unique selectivity of the overall separation, which can be tested using a mixture of compounds with a wide range of polarity. This study demonstrates a pressure tuning (PT) GC system employing a microfluidic Deans switch located at the mid-point of the two capillary columns. This PT system allowed variations of inlet-outlet pressure differences of the two columns in a range of 52-17psi for the upstream column and 31-11psi for the downstream column. Peak shifting (differential migration) of compounds due to PT difference are related to a first order regression equation in a Plackett-Burman factorial study. Increased first (upstream) column pressure drop makes the second column characteristics more significant in the coupled column retention behavior, and conversely increased second (downstream) column pressure drop makes the first column characteristics more apparent; such variation can result in component swapping between polar and non-polar compounds. The coupled column system selectivity was evaluated in terms of linear solvation energy relationship (LSER) parameters, and their relation with different pressure drop effects has been constructed by applying multivariate principle component analysis (PCA). It has been found that the coupled column PT system descriptors provide a result that shows a clear clustering of different pressure settings, somewhat intermediate between those of the two commercial columns. This is equivalent to that obtained from a conventional single-column GC analysis where the interaction energy contributed from the stationary phases can be significantly adjusted by choice of midpoint PT. This result provides a foundation for pressure differentiation for selectivity enhancement. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Assessment of ptxD gene as an alternative selectable marker for Agrobacterium-mediated maize transformation.

    Science.gov (United States)

    Nahampun, Hartinio N; López-Arredondo, Damar; Xu, Xing; Herrera-Estrella, Luis; Wang, Kan

    2016-05-01

    Bacterial phosphite oxidoreductase gene and chemical phosphite can be used as a selection system for Agrobacterium -mediated maize transformation. Application of phosphite (Phi) on plants can interfere the plant metabolic system leading to stunted growth and lethality. On the other hand, ectopic expression of the ptxD gene in tobacco and Arabidopsis allowed plants to grow in media with Phi as the sole phosphorous source. The phosphite oxidoreductase (PTXD) enzyme catalyzes the conversion of Phi into phosphate (Pi) that can then be metabolized by plants and utilized as their essential phosphorous source. Here we assess an alternative selectable marker based on a bacterial ptxD gene for Agrobacterium-mediated maize transformation. We compared the transformation frequencies of maize using either the ptxD/Phi selection system or a standard herbicide bar/bialaphos selection system. Two maize genotypes, a transformation amenable hybrid Hi II and an inbred B104, were tested. Transgene presence, insertion copy numbers, and ptxD transcript levels were analyzed and compared. This work demonstrates that the ptxD/Phi selection system can be used for Agrobacterium-mediated maize transformation of both type I and type II callus culture and achieve a comparable frequency as that of the herbicide bar/bialaphos selection system.

  12. Transposable Element-Mediated Balancing Selection at Hsp90 Underlies Embryo Developmental Variation.

    Science.gov (United States)

    Chen, Bing; Zhang, Bo; Xu, Lingling; Li, Qing; Jiang, Feng; Yang, Pengcheng; Xu, Yanan; Kang, Le

    2017-05-01

    Understanding the roles of transposable elements (TEs) in the evolution of genome and adaptation is a long-sought goal. Here, we present a new model of TE co-option, in which a TE is harnessed by an essential gene and confers local adaptation through heterozygote advantage. We characterized a human Alu-like TE family, the Lm1 elements, in the genome of the migratory locust Locusta migratoria that harbors 0.7 million copies of the elements. Scanning Lm1 insertions in the natural locust populations revealed the widespread high polymorphism of Lm1. An Lm1 was recruited into the coding region of Heat-shock protein 90 (Hsp90), an important molecular chaperone for diverse signal transduction and developmental pathways. Only heterozygotes of the allele are present in natural populations. Allele frequency increases with decreased latitudes in east coastal China, even increasing up to 76% in southern populations. Regions flanking the Lm1 insertion display clear signatures of a selective sweep linked to Lm1. The Lm1-mediated Hsp90 mutation is consequential for the embryonic development of locust. Heterozygous embryos develop faster than the wild type, particularly when cued by long-day parental photoperiod. The heterozygotes also present a reduced within-population variation in embryonic development, i.e., high developmental synchrony of embryos. The naturally occurring Hsp90 mutation could facilitate multivoltinism and developmental synchronization of the locust in southern tropical region. These results revealed a genetic mechanism behind microevolutionary changes in which balancing selection may have acted to maintain the heterozygote advantage through TE co-option in essential genes. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Functional selectivity of central Gα-subunit proteins in mediating the cardiovascular and renal excretory responses evoked by central α(2) -adrenoceptor activation in vivo.

    Science.gov (United States)

    Wainford, R D; Kapusta, D R

    2012-05-01

    Activation of brain α(2) -adrenoceptors in conscious rodents decreases heart rate (HR) and mean arterial blood pressure (MAP) and increases urine output and urinary sodium excretion. In vitro, α(2) -adrenoceptor stimulation activates Gα(i(1-3)) , Gα(o) and Gα(s) -subunit protein-gated signal transduction pathways. Here we have investigated whether these same Gα-subunit protein-gated pathways mediate the cardiovascular and renal excretory responses to central α(2) -adrenoceptor activation in conscious Sprague-Dawley rats. Rats were pre-treated by intracerebroventricular injection (i.c.v.) with an oligodeoxynucleotide (ODN) targeted to a Gα(i1) , Gα(i2) , Gα(i3) , Gα(o) , Gα(s) or a scrambled (SCR) ODN sequence (25 µg, 24 h). On the day of study, the α(2) -adrenoceptor agonist guanabenz (50 µg) or saline vehicle, was injected i.c.v. into ODN-pre-treated conscious rats. MAP and HR were recorded, and urine was collected for 150 min. In vehicle- and SCR ODN-pre-treated rats, i.c.v. guanabenz decreased MAP and HR, and produced marked diuretic and natriuretic responses. Selective ODN-mediated down-regulation of brain Gα(i2) -subunit proteins abolished the central guanabenz-induced hypotension and natriuresis. In contrast, following selective Gα(s) down-regulation, the characteristic hypotensive response to i.c.v. guanabenz was converted to an immediate increase in MAP. The bradycardic and diuretic responses to i.c.v. guanabenz were not blocked by pre-treatment with any ODN. There was functional selectivity of Gα(i2) and Gα(s) subunit protein-gated signal transduction pathways in mediating the hypotensive and natriuretic, but not bradycardic or diuretic, responses evoked by central α(2) -adrenoceptor activation in vivo. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

  14. Stacking multiple transgenes at a selected genomic site via repeated recombinase-mediated DNA cassette exchanges.

    Science.gov (United States)

    Li, Zhongsen; Moon, Bryan P; Xing, Aiqiu; Liu, Zhan-Bin; McCardell, Richard P; Damude, Howard G; Falco, S Carl

    2010-10-01

    Recombinase-mediated DNA cassette exchange (RMCE) has been successfully used to insert transgenes at previously characterized genomic sites in plants. Following the same strategy, groups of transgenes can be stacked to the same site through multiple rounds of RMCE. A gene-silencing cassette, designed to simultaneously silence soybean (Glycine max) genes fatty acid ω-6 desaturase 2 (FAD2) and acyl-acyl carrier protein thioesterase 2 (FATB) to improve oleic acid content, was first inserted by RMCE at a precharacterized genomic site in soybean. Selected transgenic events were subsequently retransformed with the second DNA construct containing a Yarrowia lipolytica diacylglycerol acyltransferase gene (DGAT1) to increase oil content by the enhancement of triacylglycerol biosynthesis and three other genes, a Corynebacterium glutamicum dihydrodipicolinate synthetase gene (DHPS), a barley (Hordeum vulgare) high-lysine protein gene (BHL8), and a truncated soybean cysteine synthase gene (CGS), to improve the contents of the essential amino acids lysine and methionine. Molecular characterization confirmed that the second RMCE successfully stacked the four overexpression cassettes to the previously integrated FAD2-FATB gene-silencing cassette. Phenotypic analyses indicated that all the transgenes expressed expected phenotypes.

  15. Implications of astrocytes in mediating the protective effects of Selective Estrogen Receptor Modulators upon brain damage

    Directory of Open Access Journals (Sweden)

    George E. Barreto

    2015-04-01

    Full Text Available Selective Estrogen Receptor Modulators (SERMs are steroidal or non-steroidal compounds that are already used in clinical practice for the treatment of breast cancer, osteoporosis and menopausal symptoms. While SERMs actions in the breast, bone, and uterus have been well characterized, their actions in the brain are less well understood. Previous works have demonstrated the beneficial effects of SERMs in different chronic neurodegenerative diseases like Alzheimer, Parkinson’s disease and Multiple sclerosis, as well as acute degeneration as stroke and traumatic brain injury. Moreover, these compounds exhibit similar protective actions as those of estradiol in the Central Nervous System, overt any secondary effect. For these reasons, in the past few years, there has been a growing interest in the neuroprotective effects exerted directly or indirectly by SERMs in the SNC. In this context, astrocytes play an important role in the maintenance of brain metabolism, and antioxidant support to neurons, thus indicating that better protection of astrocytes are an important asset targeting neuronal protection. Moreover, various clinical and experimental studies have reported that astrocytes are essential for the neuroprotective effects of SERMs during neuronal injuries, as these cells express different estrogen receptors in cell membrane, demonstrating that part of SERMs effects upon injury may be mediated by astrocytes. The present work highlights the current evidence on the protective mechanisms of SERMs, such as tamoxifen and raloxifene, in the SNC, and their modulation of astrocytic properties as promising therapeutic targets during brain damage.

  16. Selective Pressure Promotes Tetracycline Resistance of Chlamydia Suis in Fattening Pigs.

    Directory of Open Access Journals (Sweden)

    Sabrina Wanninger

    Full Text Available In pigs, Chlamydia suis has been associated with respiratory disease, diarrhea and conjunctivitis, but there is a high rate of inapparent C. suis infection found in the gastrointestinal tract of pigs. Tetracycline resistance in C. suis has been described in the USA, Italy, Switzerland, Belgium, Cyprus and Israel. Tetracyclines are commonly used in pig production due to their broad-spectrum activity and relatively low cost. The aim of this study was to isolate clinical C. suis samples in cell culture and to evaluate their antibiotic susceptibility in vitro under consideration of antibiotic treatment on herd level. Swab samples (n = 158 identified as C. suis originating from 24 farms were further processed for isolation, which was successful in 71% of attempts with a significantly higher success rate from fecal swabs compared to conjunctival swabs. The farms were divided into three treatment groups: A farms without antibiotic treatment, B farms with prophylactic oral antibiotic treatment of the whole herd consisting of trimethoprime, sulfadimidin and sulfathiazole (TSS, or C farms giving herd treatment with chlortetracycline with or without tylosin and sulfadimidin (CTS. 59 isolates and their corresponding clinical samples were selected and tested for the presence or absence of the tetracycline resistance class C gene [tet(C] by conventional PCR and isolates were further investigated for their antibiotic susceptibility in vitro. The phenotype of the investigated isolates was either classified as tetracycline sensitive (Minimum inhibitory concentration [MIC] < 2 μg/ml, intermediate (2 μg/ml ≤ MIC < 4 μg/ml or resistant (MIC ≥ 4 μg/ml. Results of groups and individual pigs were correlated with antibiotic treatment and time of sampling (beginning/end of the fattening period. We found clear evidence for selective pressure as absence of antibiotics led to isolation of only tetracycline sensitive or intermediate strains whereas tetracycline

  17. Home blood pressure monitoring and self-titration of antihypertensive medications: Proposed patient selection criteria.

    Science.gov (United States)

    Hill, James R

    2016-05-01

    Recent studies have demonstrated that home blood pressure monitoring (HBPM), coupled with self-titration of medications is a viable intervention to control hypertension. There are currently no established criteria to evaluate patients for inclusion in such a program. The purpose of this discussion is to propose criteria for determining if a patient is appropriate to participate in a program of HBPM and self-titration. Inclusion criteria for two self-titration trials were examined, and additional factors in clinical practice were identified and discussed. Additional selection criteria were proposed to support the decision to enroll a patient in an antihypertensive self-titration program. Inclusion criteria from self-titration trials provide a reasonable starting point for choosing appropriate patients in clinical practice, but additional research is necessary. Adaptation of these criteria and consideration of the identified factors can be used to develop decision support instruments. Such instruments should be evaluated for effectiveness and reliability prior to use in clinical practice. HBPM combined with self-titration is an effective patient-centered approach for hypertension management. Decision support instruments to determine appropriate patients are necessary for safe and effective use in clinical practice. ©2015 American Association of Nurse Practitioners.

  18. Humoral Immune Pressure Selects for HIV-1 CXC-chemokine Receptor 4-using Variants

    Directory of Open Access Journals (Sweden)

    Nina Lin

    2016-06-01

    Full Text Available Although both C-C chemokine receptor 5 (CCR5- and CXC chemokine receptor 4 (CXCR4-using HIV-1 strains cause AIDS, the emergence of CXCR4-utilizing variants is associated with an accelerated decline in CD4+ T cells. It remains uncertain if CXCR4-using viruses hasten disease or if these variants only emerge after profound immunological damage. We show that exclusively CXCR4- as compared to cocirculating CCR5-utilizing variants are less sensitive to neutralization by both contemporaneous autologous plasma and plasma pools from individuals that harbor only CCR5-using HIV-1. The CXCR4-utilizing variants, however, do not have a global antigenic change because they remain equivalently susceptible to antibodies that do not target coreceptor binding domains. Studies with envelope V3 loop directed antibodies and chimeric envelopes suggest that the neutralization susceptibility differences are potentially influenced by the V3 loop. In vitro passage of a neutralization sensitive CCR5-using virus in the presence of autologous plasma and activated CD4+ T cells led to the emergence of a CXCR4-utilizing virus in 1 of 3 cases. These results suggest that in some but not necessarily all HIV-1 infected individuals humoral immune pressure against the autologous virus selects for CXCR4-using variants, which potentially accelerates disease progression. Our observations have implications for using antibodies for HIV-1 immune therapy.

  19. Competitive excitation and osmotic-pressure-mediated control of lasing modes in cholesteric liquid crystal microshells

    Science.gov (United States)

    Lin, Ya-Li; Gong, Ling-Li; Che, Kai-Jun; Li, Sen-Sen; Chu, Cheng-Xu; Cai, Zhi-Ping; Yang, Chaoyong James; Chen, Lu-Jian

    2017-05-01

    We examined the end-pumped lasing behaviors of dye doped cholesteric liquid crystal (DDCLC) microshells which were fabricated by glass capillary microfluidics. Several kinds of mode resonances, including distributed feedback, Fabry-Pérot (FP), and whispering gallery (WG) modes, can be robustly constructed in each individual DDCLC microshell by varying the beam diameter, namely, tuning the DDCLC gain area. The FP and WG modes were further confirmed experimentally, and the corresponding lasing mechanisms are clearly revealed from the unique material characteristics of DDCLC and the geometrical structure of the microshell. Additionally, we demonstrated that the osmotic pressure can be used to shrink/expand the microshell, productively tuning the excitation of lasing modes in a controlled manner. We wish our findings can provide a new insight into the design of DDCLC microlasers with tunable optical properties.

  20. Preliminary materials selection issues for the next generation nuclear plant reactor pressure vessel.

    Energy Technology Data Exchange (ETDEWEB)

    Natesan, K.; Majumdar, S.; Shankar, P. S.; Shah, V. N.; Nuclear Engineering Division

    2007-03-21

    In the coming decades, the United States and the entire world will need energy supplies to meet the growing demands due to population increase and increase in consumption due to global industrialization. One of the reactor system concepts, the Very High Temperature Reactor (VHTR), with helium as the coolant, has been identified as uniquely suited for producing hydrogen without consumption of fossil fuels or the emission of greenhouse gases [Generation IV 2002]. The U.S. Department of Energy (DOE) has selected this system for the Next Generation Nuclear Plant (NGNP) Project, to demonstrate emissions-free nuclear-assisted electricity and hydrogen production within the next 15 years. The NGNP reference concepts are helium-cooled, graphite-moderated, thermal neutron spectrum reactors with a design goal outlet helium temperature of {approx}1000 C [MacDonald et al. 2004]. The reactor core could be either a prismatic graphite block type core or a pebble bed core. The use of molten salt coolant, especially for the transfer of heat to hydrogen production, is also being considered. The NGNP is expected to produce both electricity and hydrogen. The process heat for hydrogen production will be transferred to the hydrogen plant through an intermediate heat exchanger (IHX). The basic technology for the NGNP has been established in the former high temperature gas reactor (HTGR) and demonstration plants (DRAGON, Peach Bottom, AVR, Fort St. Vrain, and THTR). In addition, the technologies for the NGNP are being advanced in the Gas Turbine-Modular Helium Reactor (GT-MHR) project, and the South African state utility ESKOM-sponsored project to develop the Pebble Bed Modular Reactor (PBMR). Furthermore, the Japanese HTTR and Chinese HTR-10 test reactors are demonstrating the feasibility of some of the planned components and materials. The proposed high operating temperatures in the VHTR place significant constraints on the choice of material selected for the reactor pressure vessel for

  1. Local Irrigation Management Institutions Mediate Changes Driven by External Policy and Market Pressures in Nepal and Thailand

    Science.gov (United States)

    Bastakoti, Ram C.; Shivakoti, Ganesh P.; Lebel, Louis

    2010-09-01

    This article assesses the role of local institutions in managing irrigation water use. Fifty irrigation systems in each country were studied in Nepal and Thailand to compare the influence of local institutions on performance of irrigation systems amid changes in external policy and market pressures. Nepal’s new irrigation policy after the re-instatement of multiparty democracy in 1990 emphasized participatory irrigation management transferring the management responsibility from state authorities to water users. The water user associations of traditional farmer-managed irrigation systems were formally recognized by requiring registration with related state authorities. In Thailand also government policies encouraged people’s participation in irrigation management. Today water users are directly involved in management of even some large irrigation systems at the level of tertiary canals. Traditional communal irrigation systems in northern Thailand received support for system infrastructure improvement but have faced increased interference from government. In Thailand market development supported diversification in farming practices resulting in increased areas under high water-demanding commercial crops in the dry season. In contrast, the command areas of most irrigation systems in Nepal include cereal-based subsistence farming with only one-third having commercial farming. Cropping intensities are higher in Nepal than in Thailand reflecting, in part, differences in availability of land and management. In both countries local institutions play an important role in maintaining the performance of irrigation systems as external drivers and local contexts change. Local institutions have provided alternative options for irrigation water use by mediating external pressures.

  2. The effect of consumer pressure and abiotic stress on positive plant interactions are mediated by extreme climatic events.

    Science.gov (United States)

    Filazzola, Alessandro; Liczner, Amanda Rae; Westphal, Michael; Lortie, Christopher J

    2018-01-01

    Environmental extremes resulting from a changing climate can have profound implications for plant interactions in desert communities. Positive interactions can buffer plant communities from abiotic stress and consumer pressure caused by climatic extremes, but limited research has explored this empirically. We tested the hypothesis that the mechanism of shrub facilitation on an annual plant community can change with precipitation extremes in deserts. During years of extreme drought and above-average rainfall in a desert, we measured plant interactions and biomass while manipulating a soil moisture gradient and reducing consumer pressure. Shrubs facilitated the annual plant community at all levels of soil moisture through reductions in microclimatic stress in both years and herbivore protection in the wet year only. Shrub facilitation and the high rainfall year contributed to the dominance of a competitive annual species in the plant community. Precipitation patterns in deserts determine the magnitude and type of facilitation mechanisms. Moreover, shrub facilitation mediates the interspecific competition within the associated annual community between years with different rainfall amounts. Examining multiple drivers during extreme climate events is a challenging area of research, but it is a necessary consideration given forecasts predicting that these events will increase in frequency and magnitude. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  3. Selectivity of direct and network-mediated stimulation of the retinal ganglion cells with epi-, sub- and intraretinal electrodes

    Science.gov (United States)

    Boinagrov, David; Pangratz-Fuehrer, Susanne; Goetz, Georges; Palanker, Daniel

    2014-04-01

    Objective. Intra-retinal placement of stimulating electrodes can provide close and stable proximity to target neurons. We assessed improvement in stimulation thresholds and selectivity of the direct and network-mediated retinal stimulation with intraretinal electrodes, compared to epiretinal and subretinal placements. Approach. Stimulation thresholds of the retinal ganglion cells (RGCs) in wild-type rat retina were measured using the patch-clamp technique. Direct and network-mediated responses were discriminated using various synaptic blockers. Main results. Three types of RGC responses were identified: short latency (SL, τ 40 ms) originating in photoreceptors. Cathodic epiretinal stimulation exhibited the lowest threshold for direct RGC response and the highest direct selectivity (network/direct thresholds ratio), exceeding a factor of 3 with pulse durations below 0.5 ms. For network-mediated stimulation, the lowest threshold was obtained with anodic pulses in OPL position, and its network selectivity (direct/network thresholds ratio) increased with pulse duration, exceeding a factor of 4 at 10 ms. Latency of all three types of responses decreased with increasing strength of the stimulus. Significance. These results define the optimal range of pulse durations, pulse polarities and electrode placement for the retinal prostheses aiming at direct or network-mediated stimulation of RGCs.

  4. Evolution of cross-resistance to medical triazoles in Aspergillus fumigatus through selection pressure of environmental fungicides.

    Science.gov (United States)

    Zhang, Jianhua; van den Heuvel, Joost; Debets, Alfons J M; Verweij, Paul E; Melchers, Willem J G; Zwaan, Bas J; Schoustra, Sijmen E

    2017-09-27

    Resistance to medical triazoles in Aspergillus fumigatus is an emerging problem for patients at risk of aspergillus diseases. There are currently two presumed routes for medical triazole-resistance selection: (i) through selection pressure of medical triazoles when treating patients and (ii) through selection pressure from non-medical sterol-biosynthesis-inhibiting (SI) triazole fungicides which are used in the environment. Previous studies have suggested that SI fungicides can induce cross-resistance to medical triazoles. Therefore, to assess the potential of selection of resistance to medical triazoles in the environment, we assessed cross-resistance to three medical triazoles in lineages of A. fumigatus from previous work where we applied an experimental evolution approach with one of five different SI fungicides to select for resistance. In our evolved lines we found widespread cross-resistance indicating that resistance to medical triazoles rapidly arises through selection pressure of SI fungicides. All evolved lineages showed similar evolutionary dynamics to SI fungicides and medical triazoles, which suggests that the mutations inducing resistance to both SI fungicides and medical triazoles are likely to be the same. Whole-genome sequencing revealed that a variety of mutations were putatively involved in the resistance mechanism, some of which are in known target genes. © 2017 The Author(s).

  5. Angiotensin II Facilitates Matrix Metalloproteinase-9-Mediated Myosin Light Chain Kinase Degradation in Pressure Overload-Induced Cardiac Hypertrophy

    Directory of Open Access Journals (Sweden)

    Shun Wang

    2017-12-01

    Full Text Available Background/Aims: Angiotensin II (Ang II has been shown to promote cardiac remodeling during the process of hypertrophy. Myosin light chain kinase (MLCK, a specific kinase for the phosphorylation of myosin light chain 2 (MLC2, plays an important role in regulating cardiac muscle contraction and hypertrophy. However, whether Ang II could facilitate cardiac hypertrophy by altering the expression of MLCK remains unclear. This study aimed to investigate this effect and the underlying mechanisms. Methods: Cardiac hypertrophy was induced via pressure overload in rats, which were then evaluated via histological and biochemical measurements and echocardiography. Angiotensin-converting enzyme inhibitor (ACEI was used to inhibit Ang II. Neonatal rat cardiomyocytes were stimulated with Ang II to induce hypertrophy and were treated with a matrix metalloproteinase 9 (MMP9 inhibitor. Myocyte hypertrophy was evaluated using immunofluorescence and qRT-PCR. Degradation of recombinant human MLCK by recombinant human MMP9 was tested using a cleavage assay. The expression levels of MLCK, MLC2, phospho-myosin light chain 2 (p-MLC2, myosin phosphatase 2 (MYPT2, and calmodulin (CaM were measured using western blotting. Results: ACEI improved cardiac function and remodeling and increased the levels of MLCK and p-MLC2 as well as reduced the expression of MMP9 in pressure overload-induced cardiac hypertrophy. Moreover, the MMP9 inhibitor alleviated myocyte hypertrophy and upregulated the levels of MLCK and p-MLC2 in Ang II-induced cardiomyocyte hypertrophy. Recombinant human MLCK was concentration- and time-dependently degraded by recombinant human MMP9 in vitro, and this process was prevented by the MMP9 inhibitor. Conclusion: Our results suggest that Ang II is involved in the degradation of MLCK in pressure overload-induced cardiac hypertrophy and that this process was mediated by MMP9.

  6. Modelled in vivo HIV fitness under drug selective pressure and estimated genetic barrier towards resistance are predictive for virological response

    DEFF Research Database (Denmark)

    Deforche, Koen; Cozzi-Lepri, Alessandro; Theys, Kristof

    2008-01-01

    BACKGROUND: A method has been developed to estimate a fitness landscape experienced by HIV-1 under treatment selective pressure as a function of the genotypic sequence thereby also estimating the genetic barrier to resistance. METHODS: We evaluated the performance of two estimated fitness landsca...

  7. Effects of selective beta 1- and beta 2-adrenoreceptor agonists and antagonists on intraocular pressure in the cat.

    Science.gov (United States)

    Colasanti, B K; Trotter, R R

    1981-01-01

    Ocular tension of cats was measured after topical administration of the selective beta 1-adrenergic agonist CGP 7760B, the selective beta 1-adrenergic antagonist atenolol, the selective beta 2-adrenergic agonist salbutamol, the selective beta 2-adrenergic antagonist H 35/25, and the mixed beta 1- and beta 2-adrenergic antagonist timolol. Although atenolol did not alter intraocular pressure, CGP 7760B produced a modest decrease amounting to 3 to 4 mm Hg. Salbutamol, H 35/25, and timolol each produced a dose-dependent lowering of ocular tension, with maximal reductions amounting to 7, 5, and 5 mm Hg, respectively. Sympathetically denervated cat eyes showed supersensitivity to the pressure-lowering effect of salbutamol. In contrast, sympathectomy markedly reduced the effects of H 35/25 and timolol on ocular tension. Eyes rendered subsensitive to the pressure-lowering effects of cholinomimetics by chronic echothiophate treatment likewise showed diminished responsiveness to H 35/25 and timolol. Pretreatment with timolol (3 hr) completely abolished the pressure-lowering effect of salbutamol, and pretreatment with atenolol likewise completely antagonized the effect of CGP 7760B. These results suggest that beta-adrenergic receptors in the anterior segment of the cat eye are predominantly beta 2. Although beta-adrenergic antagonists apparently exert their effects on ocular tension by action at beta-adrenergic receptors, a cholinergic mechanism may be involved as well.

  8. NBR1-mediated selective autophagy targets insoluble ubiquitinated protein aggregates in plant stress responses.

    Directory of Open Access Journals (Sweden)

    Jie Zhou

    Full Text Available Plant autophagy plays an important role in delaying senescence, nutrient recycling, and stress responses. Functional analysis of plant autophagy has almost exclusively focused on the proteins required for the core process of autophagosome assembly, but little is known about the proteins involved in other important processes of autophagy, including autophagy cargo recognition and sequestration. In this study, we report functional genetic analysis of Arabidopsis NBR1, a homolog of mammalian autophagy cargo adaptors P62 and NBR1. We isolated two nbr1 knockout mutants and discovered that they displayed some but not all of the phenotypes of autophagy-deficient atg5 and atg7 mutants. Like ATG5 and ATG7, NBR1 is important for plant tolerance to heat, oxidative, salt, and drought stresses. The role of NBR1 in plant tolerance to these abiotic stresses is dependent on its interaction with ATG8. Unlike ATG5 and ATG7, however, NBR1 is dispensable in age- and darkness-induced senescence and in resistance to a necrotrophic pathogen. A selective role of NBR1 in plant responses to specific abiotic stresses suggest that plant autophagy in diverse biological processes operates through multiple cargo recognition and delivery systems. The compromised heat tolerance of atg5, atg7, and nbr1 mutants was associated with increased accumulation of insoluble, detergent-resistant proteins that were highly ubiquitinated under heat stress. NBR1, which contains an ubiquitin-binding domain, also accumulated to high levels with an increasing enrichment in the insoluble protein fraction in the autophagy-deficient mutants under heat stress. These results suggest that NBR1-mediated autophagy targets ubiquitinated protein aggregates most likely derived from denatured or otherwise damaged nonnative proteins generated under stress conditions.

  9. The diabetic rat kidney mediates inosituria and selective urinary partitioning of D-chiro-inositol.

    Science.gov (United States)

    Chang, Hao-Han; Choong, Bernard; Phillips, Anthony R J; Loomes, Kerry M

    2015-01-01

    Diabetic nephropathy is a serious complication of diabetes mellitus with a pressing need for effective metabolic markers to detect renal impairment. Of potential significance are the inositol compounds, myo-inositol (MI), and the less abundant stereoisomer, D-chiro-inositol (DCI), which are excreted at increased levels in the urine in diabetes mellitus, a phenomenon known as inosituria. There is also a selective urinary excretion of DCI compared to MI. As the biological origins of altered inositol metabolism in diabetes mellitus are unknown, the aim of this study was to determine whether the diabetic kidney was directly responsible. Kidneys isolated from four-week streptozotocin-induced diabetic rats were characterized by a 3-fold reduction in glomerular filtration rate (GFR) compared to matched non-diabetic kidneys. When perfused with fixed quantities of MI (50 µM) and DCI (5 µM) under normoglycemic conditions (5 mM glucose), GFR-normalized urinary excretion of MI was increased by 1.7-fold in diabetic vs. non-diabetic kidneys. By comparison, GFR-normalized urinary excretion of DCI was increased by 4-fold. Perfusion conditions replicating hyperglycemia (20 mM glucose) potentiated DCI but not MI urinary excretion in both non-diabetic and diabetic kidneys. Overall, there was a 2.4-fold increase in DCI urinary excretion compared to MI in diabetic kidneys that was independent of glucose ambience. This increased urinary excretion of DCI and MI in diabetic kidneys occurred despite increased renal expression of the inositol transporters, sodium myo-inositol transporter subtype 1 and 2 (SMIT1 and SMIT2). These findings show that the diabetic kidney primarily mediates inosituria and altered urinary partitioning of MI and DCI. Urinary inositol levels might therefore serve as an indicator of impaired renal function in diabetes mellitus with wider implications for monitoring chronic kidney disease. © 2014 by the Society for Experimental Biology and Medicine.

  10. Inhibitory effect of silver nanoparticles mediated by atmospheric pressure air cold plasma jet against dermatophyte fungi.

    Science.gov (United States)

    Ouf, Salama A; El-Adly, Amira A; Mohamed, Abdel-Aleam H

    2015-10-01

    In an in vitro study with five clinical isolates of dermatophytes, the MIC(50) and MIC(100) values of silver nanoparticles (AgNPs) ranged from 5 to 16 and from 15 to 32 μg ml(- 1), respectively. The combined treatment of AgNPs with atmospheric pressure-air cold plasma (APACP) induced a drop in the MIC(50) and MIC100 values of AgNPs reaching 3-11 and 12-23 μg ml(- 1), respectively, according to the examined species. Epidermophyton floccosum was the most sensitive fungus to AgNPs, while Trichophyton rubrum was the most tolerant. AgNPs induced significant reduction in keratinase activity and an increase in the mycelium permeability that was greater when applied combined with plasma treatment. Scanning electron microscopy showed electroporation of the cell walls and the accumulation of AgNPs on the cell wall and inside the cells, particularly when AgNPs were combined with APACP treatment. An in vivo experiment with dermatophyte-inoculated guinea pigs indicated that the application of AgNPs combined with APACP was more efficacious in healing and suppressing disease symptoms of skin as compared with the application of AgNPs alone. The recovery from the infection reached 91.7 % in the case of Microsporum canis-inoculated guinea pigs treated with 13 μg ml(- 1) AgNPs combined with APACP treatment delivered for 2  min. The emission spectra indicated that the efficacy of APACP was mainly due to generation of NO radicals and excited nitrogen molecules. These reactive species interact and block the activity of the fungal spores in vitro and in the skin lesions of the guinea pigs. The results achieved are promising compared with fluconazole as reference antifungal drug.

  11. Effects of selected thermophilic microorganisms on crude oils at elevated temperatures and pressures. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Premuzic, E.T.; Lin, M.S.

    1995-07-01

    During the past several years, a considerable amount of work has been carried out showing that microbially enhanced oil recovery (MEOR) is promising and the resulting biotechnology may be deliverable. At the Brookhaven National Laboratory (BNL), systematic studies have been conducted which dealt with the effects of thermophilic and thermoadapted bacteria on the chemical and physical properties of selected types of crude oils at elevated temperatures and pressures. Particular attention was paid to heavy crude oils from Venezuela, California, Alabama, Arkansas, Wyoming, Alaska, and other oil producing areas. Current studies indicate that during the biotreatment several chemical and physical properties of crude oils are affected. The oils are (1) emulsified; (2) acidified; (3) there is a qualitative and quantitative change in light and heavy fractions of the crudes; (4) there are chemical changes in fractions containing sulfur compounds; (5) there is an apparent reduction in the concentration of trace metals; (6) the qualitative and quantitative changes appear to be microbial species dependent; and (7) there is a distinction between {open_quotes}biodegraded{close_quotes} and {open_quotes}biotreated{close_quotes} oils. Preliminary results indicate the introduced microorganisms may become the dominant species in the bioconversion of oils. These studies also indicate the biochemical interactions between crude oils and microorganisms follow distinct trends, characterized by a group of chemical markers. Core-flooding experiments have shown significant additional crude oil recoveries are achievable with thermophilic microorganisms at elevated temperatures similar to those found in oil reservoirs. In addition, the biochemical treatment of crude oils has technological applications in downstream processing of crude oils such as in upgrading of low grade oils and the production of hydrocarbon based detergents.

  12. Widespread sequence variations in VAMP1 across vertebrates suggest a potential selective pressure from botulinum neurotoxins.

    Directory of Open Access Journals (Sweden)

    Lisheng Peng

    2014-07-01

    Full Text Available Botulinum neurotoxins (BoNT/A-G, the most potent toxins known, act by cleaving three SNARE proteins required for synaptic vesicle exocytosis. Previous studies on BoNTs have generally utilized the major SNARE homologues expressed in brain (VAMP2, syntaxin 1, and SNAP-25. However, BoNTs target peripheral motor neurons and cause death by paralyzing respiratory muscles such as the diaphragm. Here we report that VAMP1, but not VAMP2, is the SNARE homologue predominantly expressed in adult rodent diaphragm motor nerve terminals and in differentiated human motor neurons. In contrast to the highly conserved VAMP2, BoNT-resistant variations in VAMP1 are widespread across vertebrates. In particular, we identified a polymorphism at position 48 of VAMP1 in rats, which renders VAMP1 either resistant (I48 or sensitive (M48 to BoNT/D. Taking advantage of this finding, we showed that rat diaphragms with I48 in VAMP1 are insensitive to BoNT/D compared to rat diaphragms with M48 in VAMP1. This unique intra-species comparison establishes VAMP1 as a physiological toxin target in diaphragm motor nerve terminals, and demonstrates that the resistance of VAMP1 to BoNTs can underlie the insensitivity of a species to members of BoNTs. Consistently, human VAMP1 contains I48, which may explain why humans are insensitive to BoNT/D. Finally, we report that residue 48 of VAMP1 varies frequently between M and I across seventeen closely related primate species, suggesting a potential selective pressure from members of BoNTs for resistance in vertebrates.

  13. A new experimental setup for high-pressure catalytic activity measurements on surface deposited mass-selected Pt clusters

    International Nuclear Information System (INIS)

    Watanabe, Yoshihide; Isomura, Noritake

    2009-01-01

    A new experimental setup to study catalytic and electronic properties of size-selected clusters on metal oxide substrates from the viewpoint of cluster-support interaction and to formulate a method for the development of heterogeneous catalysts such as automotive exhaust catalysts has been developed. The apparatus consists of a size-selected cluster source, a photoemission spectrometer, a scanning tunneling microscope (STM), and a high-pressure reaction cell. The high-pressure reaction cell measurements provided information on catalytic properties in conditions close to practical use. The authors investigated size-selected platinum clusters deposited on a TiO 2 (110) surface using a reaction cell and STM. Catalytic activity measurements showed that the catalytic activities have a cluster-size dependency.

  14. Hyperlipidaemia is associated with increased insulin-mediated glucose metabolism, reduced fatty acid metabolism and normal blood pressure in transgenic mice overexpressing human apolipoprotein C1

    NARCIS (Netherlands)

    Koopmans, S.J.; Jong, M.C.; Que, I.; Dahlmans, V.E.H.; Pijl, H.; Radder, J.K.; Frölich, M.; Havekes, L.M.

    2001-01-01

    Aims/hypothesis. Insulin resistance for glucose metabolism is associated with hyperlipidaemia and high blood pressure. In this study we investigated the effect of primary hyperlipidaemia on basal and insulin-mediated glucose and on non-esterified fatty acid (NEFA) metabolism and mean arterial

  15. The Effectiveness of the Life Skills Program IPSY for the Prevention of Adolescent Tobacco Use: The Mediating Role of Yielding to Peer Pressure

    Science.gov (United States)

    Weichold, Karina; Tomasik, Martin J.; Silbereisen, Rainer K.; Spaeth, Michael

    2016-01-01

    In this study, the effectiveness of a life skills program to impede tobacco use in early adolescence was scrutinized. The focus was on the mediating role of yielding to peer pressure. The universal school-based life skills program IPSY (Information + Psychosocial Competence = Protection) against adolescent substance use was implemented over 3…

  16. Self-sustained carbon monoxide oxidation oscillations on size-selected platinum nanoparticles at atmospheric pressure

    DEFF Research Database (Denmark)

    Jensen, Robert; Andersen, Thomas; Nierhoff, Anders Ulrik Fregerslev

    2013-01-01

    High-quality mass spectrometry data of the oscillatory behavior of CO oxidation on SiO2 supported Pt-nanoparticles at atmospheric pressure have been acquired as a function of pressure, coverage, gas composition and nanoparticle size. The oscillations are self-sustained for several days at constant......, temperature, pressure and CO/O2 ratio. The frequency of the oscillations is very well defined and increases over time. The oscillation frequency is furthermore strongly temperature dependent with increasing temperature resulting in increasing frequency. A plausible mechanism for the oscillations is proposed...

  17. The Symmetry in the Selected Plantar Pressure Distribution Parameters of the Elderly Subject With Lower Limb Discrepancy (LLD

    Directory of Open Access Journals (Sweden)

    Raghad Memar

    2012-10-01

    Full Text Available Objectives: lower leg discrepancy is a common problem which causes the changes in the plantar pressure distribution pattern during gait. Therefore, the purpose of this study was to study the symmetry in the various plantar pressure distribution parameters in the elderly subject with leg discrepancy. Methods & Materials: Twenty-one elderly from Esfehan with leg discrepancy (1.5 to 3 cm participated in this study. Plantar pressure distribution and other related parameters were measured in the five discrete steps for each limb by “emed 2” platforms. Three successful steps from five were selected and averaged, and the plantar areas were divided into 11 marks. For each mark peak force (BW%, peak pressure (Kpa, contact area, contact time, pressure time integral and force time integral were calculated. Descriptive statistics (mean and SD to report the plantar pressure pattern, dependent sample t- test for comparison pressure data between long and short limb (P≤0.05 and symmetry index (SI% for the symmetrical status in the selected plantar pressure data of the elderly subject with LLD were used. Results: The consequence of dependent t-test showed that regardless of contact area in the forefoot region and 3th, 4th and 5th toes, there were no significant differences between long and short limb. Symmetry index (SI% also revealed that the contact time in the short limbs heel was less than long limb and peak force and peak pressure in the short limb was less in mid foot region and was greater in forefoot region than long limb. Conclusion: Given The Result Of This Study Showed That In The Short Limb, Initial Contact Time And Weight Acceptance Was Reduced, Which Cause The Increase Of The Pressure In The Forefoot And Also Which Causes The Increase Of Stress Fracture Risk In The Metatarsal Region. Therefore, It Is Suggested That LLD Subject Use Orthotic Or Shoes That Can Increase Their Heel Height And Balancing The Contact Time In The Short Limb To Resolve

  18. Selected bibliography on pressure vessels for light-water-cooled power reactors (LWRs)

    International Nuclear Information System (INIS)

    Heddleson, F.A.

    1975-01-01

    Abstracts on LWR pressure vessels are arranged in the following categories: general, design, materials technology, fabrication techniques, inspection and testing, and failures. Author, keyword, and KWIC (keyword-in-content) indices are provided. (U.S.)

  19. Satellite Earth observation data to identify anthropogenic pressures in selected protected areas

    Science.gov (United States)

    Nagendra, Harini; Mairota, Paola; Marangi, Carmela; Lucas, Richard; Dimopoulos, Panayotis; Honrado, João Pradinho; Niphadkar, Madhura; Mücher, Caspar A.; Tomaselli, Valeria; Panitsa, Maria; Tarantino, Cristina; Manakos, Ioannis; Blonda, Palma

    2015-05-01

    Protected areas are experiencing increased levels of human pressure. To enable appropriate conservation action, it is critical to map and monitor changes in the type and extent of land cover/use and habitat classes, which can be related to human pressures over time. Satellite Earth observation (EO) data and techniques offer the opportunity to detect such changes. Yet association with field information and expert interpretation by ecologists is required to interpret, qualify and link these changes to human pressure. There is thus an urgent need to harmonize the technical background of experts in the field of EO data analysis with the terminology of ecologists, protected area management authorities and policy makers in order to provide meaningful, context-specific value-added EO products. This paper builds on the DPSIR framework, providing a terminology to relate the concepts of state, pressures, and drivers with the application of EO analysis. The type of pressure can be inferred through the detection of changes in state (i.e. changes in land cover and/or habitat type and/or condition). Four broad categories of changes in state are identified, i.e. land cover/habitat conversion, land cover/habitat modification, habitat fragmentation and changes in landscape connectivity, and changes in plant community structure. These categories of change in state can be mapped through EO analyses, with the goal of using expert judgement to relate changes in state to causal direct anthropogenic pressures. Drawing on expert knowledge, a set of protected areas located in diverse socio-ecological contexts and subject to a variety of pressures are analysed to (a) link the four categories of changes in state of land cover/habitats to the drivers (anthropogenic pressure), as relevant to specific target land cover and habitat classes; (b) identify (for pressure mapping) the most appropriate spatial and temporal EO data sources as well as interpretations from ecologists and field data

  20. Oxidative stress mediated arterial dysfunction in patients with obstructive sleep apnoea and the effect of continuous positive airway pressure treatment

    Directory of Open Access Journals (Sweden)

    Del Ben Maria

    2012-07-01

    Full Text Available Abstract Background Several studies suggest an increase of oxidative stress and a reduction of endothelial function in obstructive sleep apnoea syndrome (OSAS. We assessed the association between OSAS, endothelial dysfunction and oxidative stress. Further aim was to evaluate the effect of nasal continuous positive airway pressure (nCPAP on oxidative stress and arterial dysfunction. Methods We studied 138 consecutive patients with heavy snoring and possible OSAS. Patients underwent unattended overnight home polysomnography. Ten patients with severe OSAS were revaluated after 6 months of nCPAP therapy. To assess oxidative stress in vivo, we measured urinary 8-iso-PGF2α and serum levels of soluble NOX2-derived peptide (sNOX2-dp. Serum levels of nitrite/nitrate (NOx were also determined. Flow-mediated brachial artery dilation (FMD was measured to asses endothelial function. Results Patients with severe OSAS had higher urinary 8-iso-PGF2α (p Conclusions The results of our study indicate that patients with OSAS and cardiometabolic comorbidities have increased oxidative stress and arterial dysfunction that are partially reversed by nCPAP treatment.

  1. Selection of suitable diagnostic techniques for an RF atmospheric pressure plasma

    International Nuclear Information System (INIS)

    Kong, M.G.; Deng, X.T.

    2001-01-01

    As an early report of our study, this paper summaries the RF atmospheric pressure plasma system we intend to characterize and a number of diagnostic techniques presently under assessment for our plasma rig. By discussing the advantages and disadvantages of these diagnostic techniques at this meeting, we hope to gain feedback and comments to improve our choice of appropriate diagnostic techniques as well as our subsequent application of these techniques to nonthermal RF atmospheric pressure plasmas

  2. Population pressure and human carrying capacity in selected locations of Machakos and Kitui districts.

    Science.gov (United States)

    Bernard, F E; Thom, D J

    1981-04-01

    The nature and magnitude of population pressure in Machakos and Kitui Districts of Kenya were investigated. Specific study objectives were: 1) to examine the roots and evolution of the problem; 2) to compute carrying capacity for a sample of locations and ecozones in the 2 districts; and 3) to consider agricultural and demographic implications of the findings. Carrying capacity is defined as the number of people and the level of their activities which a region is able to sustain in perpetuity at an acceptable quality of life and without land deterioration. A methodology for calculating human carrying capacity utilizing crude soil, ecological, crop yield, and land use data for 41 locations in Machakos and Kitui Districts is demonstrated. Analysis and a comparison of population carrying capacities within the study area reveals that Machakos has reached a critical level of population pressure. To the north in Mbere and eastward in Kitui there are areas that are not currently experiencing population pressure, but it is likely that as the pressure in western Machakos becomes more acute, movement into these adjacent lands of relatively sparse settlement will increase. Signs of environmental stress resulting from overpopulation are evident throughout Machakos. The methodology used for estimating population pressure provided reasonably accurate carrying capacity estimates, but the methodology could be refined. Vigorous efforts to rejuvenate the land through soil and water conservation have been undertaken, but these have been insufficient and must be increased. Such efforts will fail unless the basic problem of population pressure in the marginal lands is resolved.

  3. Studies of selected transuranium and lanthanide tri-iodides under pressure using absorption spectrophotometry

    International Nuclear Information System (INIS)

    Haire, R.G.; Young, J.P.; Peterson, J.R.; Tennessee Univ., Knoxville; Benedict, U.

    1987-01-01

    The anhydrous tri-iodides of plutonium, americium and curium under pressure have been investigated using absorption spectrophotometry. These initial studies on plutonium and curium tri-iodides together with the published data for americium tri-iodide show that the rhombohedral form of these compounds (BiI 3 -type structure) can be converted to the orthorhombic form (PuBr 3 -type structure) by applying pressure at room temperature. Absorption spectrophotometry can often differentiate between two crystallographic forms of a material and has been used in the present high-pressure studies to monitor the effects of pressure on the tri-iodides. A complication in these studies of the tri-iodides is a significant shift of their absorption edges with pressure from the near UV to the visible spectral region. With curium tri-iodide this shift causes interference with the major f-f absorption peaks and precludes identification by absorption spectrophotometry of the high pressure phase of CmI 3 . (orig.)

  4. Selective Tissue Distribution Mediates Tissue-Dependent PPARγ Activation and Insulin Sensitization by INT131, a Selective PPARγ Modulator

    Science.gov (United States)

    Xie, Xinni; Chen, Wei; Zhang, Ning; Yuan, Mei; Xu, Cheng; Zheng, Zhibing; Li, Hua; Wang, Lili

    2017-01-01

    The mechanisms underlying the enhancement of insulin sensitivity by selective peroxisome proliferator-activated receptor γ modulators (sPPARγMs) are still not completely known. Here, the representative sPPARγM, INT131, was used as a probe to investigate the insulin-sensitizing mechanisms of sPPARγM in the context of tissue selective compound distribution and PPARγ regulation. First, 30 mg kg−1 INT131 was observed to produce an insulin-sensitizing effect comparable to that of 10 mg kg−1 rosiglitazone (RSG) in both db/db and DIO mice using the oral glucose and insulin tolerance tests. Similar to RSG, INT131 significantly increased brown adipose tissue (BAT) mass and adipocyte size and up-regulated the expression of BAT-specific genes. Compared with RSG, INT131 exhibited greater potency in inducing white adipose tissue (WAT) browning, decreasing adipocyte size, and increasing BAT-specific and function-related gene expression in subcutaneous WAT (sWAT). However, it did not induce hepatomegaly or hepatic steatosis, which is associated with lower levels of lipogenic genes expression. Pharmacokinetic analysis reveals that in contrast with RSG, INT131 shows higher Cmax, and much longer residency time (AUC0−12h), as well relatively lower elimination rate in adipose tissues and skeletal muscle, this demonstrated INT131 distributed predominantly in adipose tissue. Whereas, INT131 was less abundant in the liver. These results thus suggest that the tissue-selective distribution underlies INT131's selective PPARγ modulation. Compounds favoring adipose tissue may aid in development of better, safer sPPARγM to address the insulin resistance of diabetes. PMID:28611668

  5. Selective Tissue Distribution Mediates Tissue-Dependent PPARγ Activation and Insulin Sensitization by INT131, a Selective PPARγ Modulator

    Directory of Open Access Journals (Sweden)

    Xinni Xie

    2017-05-01

    Full Text Available The mechanisms underlying the enhancement of insulin sensitivity by selective peroxisome proliferator-activated receptor γ modulators (sPPARγMs are still not completely known. Here, the representative sPPARγM, INT131, was used as a probe to investigate the insulin-sensitizing mechanisms of sPPARγM in the context of tissue selective compound distribution and PPARγ regulation. First, 30 mg kg−1 INT131 was observed to produce an insulin-sensitizing effect comparable to that of 10 mg kg−1 rosiglitazone (RSG in both db/db and DIO mice using the oral glucose and insulin tolerance tests. Similar to RSG, INT131 significantly increased brown adipose tissue (BAT mass and adipocyte size and up-regulated the expression of BAT-specific genes. Compared with RSG, INT131 exhibited greater potency in inducing white adipose tissue (WAT browning, decreasing adipocyte size, and increasing BAT-specific and function-related gene expression in subcutaneous WAT (sWAT. However, it did not induce hepatomegaly or hepatic steatosis, which is associated with lower levels of lipogenic genes expression. Pharmacokinetic analysis reveals that in contrast with RSG, INT131 shows higher Cmax, and much longer residency time (AUC0−12h, as well relatively lower elimination rate in adipose tissues and skeletal muscle, this demonstrated INT131 distributed predominantly in adipose tissue. Whereas, INT131 was less abundant in the liver. These results thus suggest that the tissue-selective distribution underlies INT131's selective PPARγ modulation. Compounds favoring adipose tissue may aid in development of better, safer sPPARγM to address the insulin resistance of diabetes.

  6. Selective extraction of hydrocarbons, phosphonates and phosphonic acids from soils by successive supercritical fluid and pressurized liquid extractions.

    Science.gov (United States)

    Chaudot, X; Tambuté, A; Caude, M

    2000-01-14

    Hydrocarbons, dialkyl alkylphosphonates and alkyl alkylphosphonic acids are selectively extracted from spiked soils by successive implementation of supercritical carbon dioxide, supercritical methanol-modified carbon dioxide and pressurized water. More than 95% of hydrocarbons are extracted during the first step (pure supercritical carbon dioxide extraction) whereas no organophosphorus compound is evidenced in this first extract. A quantitative extraction of phosphonates is achieved during the second step (methanol-modified supercritical carbon dioxide extraction). Polar phosphonic acids are extracted during a third step (pressurized water extraction) and analyzed by gas chromatography under methylated derivatives (diazomethane derivatization). Global recoveries for these compounds are close to 80%, a loss of about 20% occurring during the derivatization process (co-evaporation with solvent). The developed selective extraction method was successfully applied to a soil sample during an international collaborative exercise.

  7. Microbial selection pressure is not a prerequisite for granulation: dynamic granulation and microbial community study in a complete mixing bioreactor.

    Science.gov (United States)

    Zhou, Dandan; Niu, Shu; Xiong, Yongjiao; Yang, Yang; Dong, Shuangshi

    2014-06-01

    Microbial selection pressure is traditionally supposed as a prerequisite for aerobic granulation. This work gives a different insight on this issue. Fluorescent microspheres were used to label the flocculent biomass granulation for a period of 47days in a continuous-flow bioreactor. Analysis of the distribution of fluorescent microspheres in granules revealed that the terminal phase of granulation is in a dynamic steady state, where bioflocs detach, collide and aggregate randomly. This revealed that the un-granulated biomass was the result of the dynamic aggregation and breakage, rather than the microbial species unable to be granulated. Furthermore, denaturing gradient gel electrophoresis (DGGE) profile and UPGMA dendrogram results showed similar microbial communities during the granulation. To sum up, microbial selection pressure was not a prerequisite for aerobic granulation from both of the dynamic granulation steps and molecular biology aspects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Osimertinib (AZD9291, a Mutant-Selective EGFR Inhibitor, Reverses ABCB1-Mediated Drug Resistance in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xiao-Yu Zhang

    2016-09-01

    Full Text Available In recent years, tyrosine kinase inhibitors (TKIs have been shown capable of inhibiting the ATP-binding cassette (ABC transporter-mediated multidrug resistance (MDR. In this study, we determine whether osimertinib, a novel selective, irreversible EGFR (epidermal growth factor receptor TKI, could reverse ABC transporter-mediated MDR. The results showed that, at non-toxic concentrations, osimertinib significantly sensitized both ABCB1-transfected and drug-selected cell lines to substrate anticancer drugs colchicine, paclitaxel, and vincristine. Osimertinib significantly increased the accumulation of [3H]-paclitaxel in ABCB1 overexpressing cells by blocking the efflux function of ABCB1 transporter. In contrast, no significant alteration in the expression levels and localization pattern of ABCB1 was observed when ABCB1 overexpressing cells were exposed to 0.3 µM osimertinib for 72 h. In addition, ATPase assay showed osimertinib stimulated ABCB1 ATPase activity. Molecular docking and molecular dynamic simulations showed osimertinib has strong and stable interactions at the transmembrane domain of human homology ABCB1. Taken together, our findings suggest that osimertinib, a clinically-approved third-generation EGFR TKI, can reverse ABCB1-mediated MDR, which supports the combination therapy with osimertinib and ABCB1 substrates may potentially be a novel therapeutic stategy in ABCB1-positive drug resistant cancers.

  9. Changes in selective pressures associated with human population expansion may explain metabolic and immune related pathways enriched for signatures of positive selection.

    Science.gov (United States)

    Vatsiou, Alexandra I; Bazin, Eric; Gaggiotti, Oscar E

    2016-07-21

    The study of local adaptation processes is a very important research topic in the field of population genomics. There is a particular interest in the study of human populations because they underwent a process of rapid spatial expansion and faced important environmental changes that translated into changes in selective pressures. New mutations may have been selected for in the new environment and previously existing genetic variants may have become detrimental. Immune related genes may have been released from the selective pressure exerted by pathogens in the ancestral environment and new variants may have been positively selected due to pathogens present in the newly colonized habitat. Also, variants that had a selective advantage in past environments may have become deleterious in the modern world due to external stimuli including climatic, dietary and behavioral changes, which could explain the high prevalence of some polygenic diseases such as diabetes and obesity. We performed an enrichment analysis to identify gene sets enriched for signals of positive selection in humans. We used two genome scan methods, XPCLR and iHS to detect selection using a dense coverage of SNP markers combined with two gene set enrichment approaches. We identified immune related gene sets that could be involved in the protection against pathogens especially in the African population. We also identified the glycolysis & gluconeogenesis gene set, related to metabolism, which supports the thrifty genotype hypothesis invoked to explain the current high prevalence of diseases such as diabetes and obesity. Extending our analysis to the gene level, we found signals for 23 candidate genes linked to metabolic syndrome, 13 of which are new candidates for positive selection. Our study provides a list of genes and gene sets associated with immunity and metabolic syndrome that are enriched for signals of positive selection in three human populations (Europeans, Africans and Asians). Our results

  10. Pressurized liquid extraction of selected molecular biomarkers in deep sea sediments used as proxies in paleoceanography.

    Science.gov (United States)

    Calvo, Eva; Pelejero, Carles; Logan, Graham A

    2003-03-14

    Pressurized liquid extraction has been performed on a suite of deep-sea sediments to assess its capability as an extraction technique in the analysis of molecular biomarkers used in paleoceanography. Specific compounds assessed comprise long-chain alkenones, n-alkanes, n-alcohols and, additionally, one diol and one keto-ol. These have been extracted by both pressurized liquid extraction and ultrasonication for comparison. One key result is that the U37(K') index (based on the degree of unsaturation of the alkenones and used as a paleothermometer in paleoceanography) remains intact after both extraction techniques. In terms of biomarker concentrations, which are often used to qualitatively assess changes in marine productivity and/or terrigenous inputs, pressurized liquid extraction is substantially more efficient than ultrasonication, providing higher amounts of extracted constituents, particularly for polar compounds.

  11. Selective Heart Rate Reduction With Ivabradine Increases Central Blood Pressure in Stable Coronary Artery Disease.

    Science.gov (United States)

    Rimoldi, Stefano F; Messerli, Franz H; Cerny, David; Gloekler, Steffen; Traupe, Tobias; Laurent, Stéphane; Seiler, Christian

    2016-06-01

    Heart rate (HR) lowering by β-blockade was shown to be beneficial after myocardial infarction. In contrast, HR lowering with ivabradine was found to confer no benefits in 2 prospective randomized trials in patients with coronary artery disease. We hypothesized that this inefficacy could be in part related to ivabradine's effect on central (aortic) pressure. Our study included 46 patients with chronic stable coronary artery disease who were randomly allocated to placebo (n=23) or ivabradine (n=23) in a single-blinded fashion for 6 months. Concomitant baseline medication was continued unchanged throughout the study except for β-blockers, which were stopped during the study period. Central blood pressure and stroke volume were measured directly by left heart catheterization at baseline and after 6 months. For the determination of resting HR at baseline and at follow-up, 24-hour ECG monitoring was performed. Patients on ivabradine showed an increase of 11 mm Hg in central systolic pressure from 129±22 mm Hg to 140±26 mm Hg (P=0.02) and in stroke volume by 86±21.8 to 107.2±30.0 mL (P=0.002). In the placebo group, central systolic pressure and stroke volume remained unchanged. Estimates of myocardial oxygen consumption (HR×systolic pressure and time-tension index) remained unchanged with ivabradine.The decrease in HR from baseline to follow-up correlated with the concomitant increase in central systolic pressure (r=-0.41, P=0.009) and in stroke volume (r=-0.61, Pcoronary artery disease patients. CLINICAL TRIALSURL: http://www.clinicaltrials.gov. Unique identifier NCT01039389. © 2016 American Heart Association, Inc.

  12. Polyandry as a mediator of sexual selection before and after mating.

    Science.gov (United States)

    Kvarnemo, Charlotta; Simmons, Leigh W

    2013-03-05

    The Darwin-Bateman paradigm recognizes competition among males for access to multiple mates as the main driver of sexual selection. Increasingly, however, females are also being found to benefit from multiple mating so that polyandry can generate competition among females for access to multiple males, and impose sexual selection on female traits that influence their mating success. Polyandry can reduce a male's ability to monopolize females, and thus weaken male focused sexual selection. Perhaps the most important effect of polyandry on males arises because of sperm competition and cryptic female choice. Polyandry favours increased male ejaculate expenditure that can affect sexual selection on males by reducing their potential reproductive rate. Moreover, sexual selection after mating can ameliorate or exaggerate sexual selection before mating. Currently, estimates of sexual selection intensity rely heavily on measures of male mating success, but polyandry now raises serious questions over the validity of such approaches. Future work must take into account both pre- and post-copulatory episodes of selection. A change in focus from the products of sexual selection expected in males, to less obvious traits in females, such as sensory perception, is likely to reveal a greater role of sexual selection in female evolution.

  13. Digoxin derivatives with selectivity for the α2β3 isoform of Na,K-ATPase potently reduce intraocular pressure.

    Science.gov (United States)

    Katz, Adriana; Tal, Daniel M; Heller, Dan; Habeck, Michael; Ben Zeev, Efrat; Rabah, Bilal; Bar Kana, Yaniv; Marcovich, Arie L; Karlish, Steven J D

    2015-11-03

    The ciliary epithelium in the eye consists of pigmented epithelial cells that express the α1β1 isoform of Na,K-ATPase and nonpigmented epithelial cells that express mainly the α2β3 isoform. In principle, a Na,K-ATPase inhibitor with selectivity for α2β3 that penetrates the cornea could effectively reduce intraocular pressure, with minimal systemic or local toxicity. We have recently synthesized perhydro-1,4-oxazepine derivatives of digoxin by NaIO4 oxidation of the third digitoxose and reductive amination with various R-NH2 substituents and identified derivatives with significant selectivity for human α2β1 over α1β1 (up to 7.5-fold). When applied topically, the most α2-selective derivatives effectively prevented or reversed pharmacologically raised intraocular pressure in rabbits. A recent structure of Na,K-ATPase, with bound digoxin, shows the third digitoxose approaching one residue in the β1 subunit, Gln84, suggesting a role for β in digoxin binding. Gln84 in β1 is replaced by Val88 in β3. Assuming that alkyl substituents might interact with β3Val88, we synthesized perhydro-1,4-oxazepine derivatives of digoxin with diverse alkyl substituents. The methylcyclopropyl and cyclobutyl derivatives are strongly selective for α2β3 over α1β1 (22-33-fold respectively), as determined either with purified human isoform proteins or intact bovine nonpigmented epithelium cells. When applied topically on rabbit eyes, these derivatives potently reduce both pharmacologically raised and basal intraocular pressure. The cyclobutyl derivative is more efficient than Latanoprost, the most widely used glaucoma drug. Thus, the conclusion is that α2β3-selective digoxin derivatives effectively penetrate the cornea and inhibit the Na,K-ATPase, hence reducing aqueous humor production. The new digoxin derivatives may have potential for glaucoma drug therapy.

  14. Data describing the flow-mediated vasodilation responses and blood pressure in young adult humans after a single dose of oral edible emu oil

    Directory of Open Access Journals (Sweden)

    Tadayoshi Miyashita

    2018-04-01

    Full Text Available The data provided herein include flow-mediated vasodilation responses, represented by changes in arterial diameter, and blood pressure in young adults after a single oral dose of edible emu oil or placebo (cross-over design. Ten healthy men and 10 healthy women participated. Increased blood flow in the antebrachial region was induced by inflating a pressure cuff and subsequently releasing the pressure by deflating the cuff. After the release, the arterial diameter was continuously monitored for 110 sec using ultrasonic diagnostic equipment. The changes in the arterial diameter from 20 to 110 sec post-cuff deflation are described in line graphs and tables. In addition, systolic and diastolic blood pressure data are provided in a table.

  15. Simulation of Energy Selective signal Amplification in Gas Environment of Variable Pressure SEM

    Czech Academy of Sciences Publication Activity Database

    Neděla, Vilém; Konvalina, Ivo; Lencová, B.; Zlámal, J.

    2011-01-01

    Roč. 17, Suppl. 2 (2011), s. 920-921 ISSN 1431-9276 R&D Projects: GA ČR GAP102/10/1410 Institutional research plan: CEZ:AV0Z20650511 Keywords : variable pressure scanning electron microscopes (VP-SEM) * AQUASEM II * simlulation Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 3.007, year: 2011

  16. Pump selection and application in a pressurized water reactor electric generating plant

    International Nuclear Information System (INIS)

    Kitch, D.M.

    1985-01-01

    Various pump applications utilized in a nuclear pressurized water reactor electric generating plant are described. Emphasis is on pumps installed in the auxiliary systems of the primary nuclear steam supply system. Hydraulic and mechanical details, the ASME Code (Nuclear Design), materials, mechanical seals, shaft design, seismic qualification, and testing are addressed

  17. The use of phosphomannose isomerase selection system for Agrobacterium-mediated transformation of tobacco and flax aimed for phytoremediation.

    Science.gov (United States)

    Hilgert, Jitka; Sura-De Jong, Martina; Fišer, Jiří; Tupá, Kateřina; Vrbová, Miroslava; Griga, Miroslav; Macek, Tomáš; Žiarovská, Jana

    2017-05-04

    A plant selection system based on the phosphomannose isomerase gene (pmi) as a selectable marker is often used to avoid selection using antibiotic resistance. Nevertheless, pmi gene is endogenous in several plant species and therefore difficult to use in such cases. Here we evaluated and compared Agrobacterium-mediated transformation of Linum usitatissimum breeding line AGT-952 (without endogenous pmi gene) and Nicotiana tabacum var. WSC-38 (with endogenous pmi gene). Transformation was evaluated for vectors bearing transgenes that have the potential to be involved in improved phytoremediation of contaminated environment. Tobacco regenerants selection resulted in 6.8% transformation efficiency when using a medium supplemented with 30 g/L mannose with stepwise decrease of the sucrose concentration. Similar transformation efficiency (5.3%) was achieved in transformation of flax. Relatively low selection efficiency was achieved (12.5% and 34.8%, respectively). The final detection of efficient pmi selection was conducted using PCR and the non-endogenous genes; pmi transgene for flax and todC2 transgene for tobacco plants.

  18. Oncologist burnout and compassion fatigue: investigating time pressure at work as a predictor and the mediating role of work-family conflict.

    Science.gov (United States)

    Kleiner, Sibyl; Wallace, Jean E

    2017-09-11

    Oncologists are at high risk of poor mental health. Prior research has focused on burnout, and has identified heavy workload as a key predictor. Compassion fatigue among physicians has generally received less attention, although medical specialties such as oncology may be especially at risk of compassion fatigue. We contribute to research by identifying predictors of both burnout and compassion fatigue among oncologists. In doing so, we distinguish between quantitative workload (e.g., work hours) and subjective work pressure, and test whether work-family conflict mediates the relationships between work pressure and burnout or compassion fatigue. In a cross-sectional study, oncologists from across Canada (n = 312) completed questionnaires assessing burnout, compassion fatigue, workload, time pressure at work, work-family conflict, and other personal, family, and occupational characteristics. Analyses use Ordinary Least Squares regression. Subjective time pressure at work is a key predictor of both burnout and compassion fatigue. Our results also show that work-family conflict fully mediates these relationships. Overall, the models explain more of the variation in burnout as compared to compassion fatigue. Our study highlights the need to consider oncologists' subjective time pressure, in addition to quantitative workload, in interventions to improve mental health. The findings also highlight a need to better understand additional predictors of compassion fatigue.

  19. Data on a single oral dose of camu camu (Myrciaria dubia pericarp extract on flow-mediated vasodilation and blood pressure in young adult humans

    Directory of Open Access Journals (Sweden)

    Tadayoshi Miyashita

    2018-02-01

    Full Text Available This data article describes the flow-mediated vasodilation (FMD responses, represented by changes in arterial diameter, and blood pressure changes in young adults after a single oral dose of camu camu (Myrciaria dubia pericarp extract or placebo (cross-over design. Ten healthy men and 10 healthy women participated in this study. Ultrasonic diagnostic equipment was used to monitor arterial diameter changes, indicative of FMD, for 110 s after the administration of the camu camu extract or placebo. In addition, the systolic and diastolic blood pressure values were recorded.

  20. Copper resistance in Enterococcus faecium, mediated by the tcrB gene, is selected by supplementation of pig feed with copper sulfate

    DEFF Research Database (Denmark)

    Hasman, Henrik; Kempf, I.; Chidaine, B.

    2006-01-01

    The tcr gene cluster mediates in vitro copper resistance in Enterococcus faecium. Here we describe the selection of tcr-mediated copper resistance in E. faecium in an animal feeding experiment with young pigs fed 175 mg copper/kg feed (ppm), which is the concentration commonly used for piglets...

  1. Algae-mediated removal of selected pharmaceutical and personal care products (PPCPs) from Lake Mead water.

    Science.gov (United States)

    Bai, Xuelian; Acharya, Kumud

    2017-03-01

    The persistence and fate of pharmaceutical and personal care products (PPCPs) in the Lake Mead ecosystem are particularly important considering the potential ecological risks and human health impacts. This study evaluated the removal of five common PPCPs (i.e., trimethoprim, sulfamethoxazole, carbamazepine, ciprofloxacin, and triclosan) from Lake Mead water mediated by the green alga Nannochloris sp. The results from the incubation studies showed that trimethoprim and carbamazepine were highly resistant to uptake in the algal cultural medium and were measured at approximately 90%-100% of the applied dose after 14days of incubation. Sulfamethoxazole was found relatively persistent, with >60% of the applied dose remaining in the water after 14days, and its removal was mainly caused by algae-mediated photolysis. However, ciprofloxacin and triclosan dissipated significantly and nearly 100% of the compounds were removed from the water after 7days of incubation under 24h of light. Ciprofloxacin and triclosan were highly susceptible to light, and their estimated half-lives were 12.7hours for ciprofloxacin and 31.2hours for triclosan. Algae-mediated sorption contributed to 11% of the removal of trimethoprim and sulfamethoxazole, 13% of the removal of carbamazepine, and 27% of the removal of triclosan from the lake water. This research showed that 1) trimethoprim, sulfamethoxazole, and carbamazepine are quite persistent in aquatic environments and may potentially affect human health via drinking water intake; 2) photolysis is the dominant pathway to remove ciprofloxacin from aquatic ecosystems, which indicates that ciprofloxacin may have lower ecological risks compared with other PPCPs; and 3) triclosan can undergo photolysis as well as algae-mediated uptake and it may potentially affect the food web because of its high toxicity to aquatic species. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Octene hydroformylation by using rhodium complexes tethered onto selectively functionalized mesoporous silica and in-situ high pressure IR study

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ki-Chang; Baek, Ji Yeon; Bae, Jung A.; Yim, Jin-Heong; Ko, Young Soo; Kim, Do Heui; Park, Young-Kwon; Jeon, Jong Ki

    2011-04-30

    SBA-15-based heterogeneous catalysts were applied to 1-octene hydroformylation. The turn over frequency over SBA-15/γ-aminopropylmethyldimethoxysilane(AEAPMDMS)/Rh catalyst with triphenylphosphine (TPP) ligand prepared by conventional post grafting method was higher than that of the homogeneous catalyst, (Rh(CH3COO)2)2 with TPP. The SBA-15/AEAPMDMS/Rh catalyst can be easily recycled without rhodium loss. The molar ratio of linear to branched nonyl aldehydes was remarkably enhanced over the heterogeneous catalysts. The selectively functionalized rhodium catalyst (SBA-15/Ph2Si(OEt)2/AEAPMDMS/Rh), in which rhodium was selectively tethered intra-pore of SBA-15, was beneficial for improving the selectivity to linear aldehyde. In situ high pressure FT-IR analysis suggested HRh(CO)2(PPh3)2 and HRh(CO)(PPh3)3 to be active species over the SBA-15/AEAPMDMS/Rh catalyst with TPP.

  3. Click-Chemistry-Mediated Synthesis of Selective Melanocortin Receptor 4 Agonists

    DEFF Research Database (Denmark)

    Palmer, Daniel; Gonçalves, Juliana P.L.; Hansen, Louise V.

    2017-01-01

    were synthesized by solid phase click chemistry to develop novel, potent, selective MC4R agonists. Using cAMP measurements and a transcriptional reporter assay, we observed that several constrained agonists generated by a cycloaddition reaction displayed high selectivity (223- to 467-fold) toward MC4R...

  4. Strength of Selection Pressure Is an Important Parameter Contributing to the Complexity of Antibiotic Resistance Evolution

    Science.gov (United States)

    Oz, Tugce; Guvenek, Aysegul; Yildiz, Sadik; Karaboga, Enes; Tamer, Yusuf Talha; Mumcuyan, Nirva; Ozan, Vedat Burak; Senturk, Gizem Hazal; Cokol, Murat; Yeh, Pamela; Toprak, Erdal

    2014-01-01

    Revealing the genetic changes responsible for antibiotic resistance can be critical for developing novel antibiotic therapies. However, systematic studies correlating genotype to phenotype in the context of antibiotic resistance have been missing. In order to fill in this gap, we evolved 88 isogenic Escherichia coli populations against 22 antibiotics for 3 weeks. For every drug, two populations were evolved under strong selection and two populations were evolved under mild selection. By quantifying evolved populations’ resistances against all 22 drugs, we constructed two separate cross-resistance networks for strongly and mildly selected populations. Subsequently, we sequenced representative colonies isolated from evolved populations for revealing the genetic basis for novel phenotypes. Bacterial populations that evolved resistance against antibiotics under strong selection acquired high levels of cross-resistance against several antibiotics, whereas other bacterial populations evolved under milder selection acquired relatively weaker cross-resistance. In addition, we found that strongly selected strains against aminoglycosides became more susceptible to five other drug classes compared with their wild-type ancestor as a result of a point mutation on TrkH, an ion transporter protein. Our findings suggest that selection strength is an important parameter contributing to the complexity of antibiotic resistance problem and use of high doses of antibiotics to clear infections has the potential to promote increase of cross-resistance in clinics. PMID:24962091

  5. Agrobacterium-mediated co-transformation of rice using two selectable marker genes derived from rice genome components.

    Science.gov (United States)

    Wakasa, Yuhya; Ozawa, Kenjirou; Takaiwa, Fumio

    2012-11-01

    A method for Agrobacterium-mediated co-transformation of rice (Oryza sativa L.) was developed using rice-derived selection markers. Two T-DNAs were efficiently introduced into separate loci using selectable marker gene cassettes consisting of the mutated acetolactate synthase gene (mALS) under the control of the callus-specific promoter (CSP) (CSP:mALS) and the ferredoxin nitrite reductase gene (NiR) under the control of its own promoter (NiR P:NiR). The CSP:mALS gene cassette confers sulfonylurea herbicide resistance to transgenic rice callus. The NiR P:NiR construct complements NiR-deficient mutant cultivars such as 'Koshihikari', which are defective in the regulation of nitrogen metabolism. In the present study, the CaMV35S:GUS and CaMV35S:GFP gene cassettes were co-introduced into the 'Koshihikari' genome using our system. Approximately 5-10 independent transgenic lines expressing both the GUS and GFP reporters were obtained from 100 Agrobacterium co-inoculated calli. Furthermore, transgenic 'Koshihikari' rice lines with reduced content of two major seed allergen proteins, the 33 and 14-16 kDa allergens, were generated by this co-transformation system. The present results indicate that the generation of selectable antibiotic resistance marker gene-free transgenic rice is possible using our rice-derived selection marker co-transformation system. Key message An improved rice transformation method was developed based on Agrobacterium-mediated co-transformation using two rice genome-derived selectable marker gene cassettes.

  6. Evidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to antibiotic- and nonantibiotic-related pressure.

    Science.gov (United States)

    Osório, Nuno S; Rodrigues, Fernando; Gagneux, Sebastien; Pedrosa, Jorge; Pinto-Carbó, Marta; Castro, António G; Young, Douglas; Comas, Iñaki; Saraiva, Margarida

    2013-06-01

    Tuberculosis (TB) is a global health problem estimated to kill 1.4 million people per year. Recent advances in the genomics of the causative agents of TB, bacteria known as the Mycobacterium tuberculosis complex (MTBC), have allowed a better comprehension of its population structure and provided the foundation for molecular evolution analyses. These studies are crucial for a better understanding of TB, including the variation of vaccine efficacy and disease outcome, together with the emergence of drug resistance. Starting from the analysis of 73 publicly available genomes from all the main MTBC lineages, we have screened for evidences of positive selection, a set of 576 genes previously associated with drug resistance or encoding membrane proteins. As expected, because antibiotics constitute strong selective pressure, some of the codons identified correspond to the position of confirmed drug-resistance-associated substitutions in the genes embB, rpoB, and katG. Furthermore, we identified diversifying selection in specific codons of the genes Rv0176 and Rv1872c coding for MCE1-associated transmembrane protein and a putative l-lactate dehydrogenase, respectively. Amino acid sequence analyses showed that in Rv0176, sites undergoing diversifying selection were in a predicted antigen region that varies between "modern" lineages and "ancient" MTBC/BCG strains. In Rv1872c, some of the sites under selection are predicted to impact protein function and thus might result from metabolic adaptation. These results illustrate that diversifying selection in MTBC is happening as a consequence of both antibiotic treatment and other evolutionary pressures.

  7. Digest: Plants adapt under attack: genotypic selection and phenotypic plasticity under herbivore pressure.

    Science.gov (United States)

    Hawkins, Nichola J

    2018-03-31

    Plant species adapt to changing environmental conditions through phenotypic plasticity and natural selection. Agrawal et al. (2018) found that dandelions responded to the presence of insect pests by producing higher levels of defensive compounds. This defensive response resulted both from phenotypic plasticity, with individual plants' defenses triggered by insect attack, and from evolution by natural selection acting on genetic variation in the plant population. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

  8. Direction selectivity in the larval zebrafish tectum is mediated by asymmetric inhibition

    Directory of Open Access Journals (Sweden)

    Abhinav eGrama

    2012-09-01

    Full Text Available The extraction of the direction of motion is an important computation performed by many sensory systems and in particular, the mechanism by which direction selective ganglion cells (DS-RGCs in the retina acquire their selective properties, has been studied extensively. However, whether DS-RGCs simply relay this information to downstream areas or whether additional and potentially de-novo processing occurs in these recipient structures is a matter of great interest. Neurons in the larval zebrafish tectum, the largest retino-recipent area in this animal, show direction selective responses to moving visual stimuli but how these properties are acquired is still unknown. In order to study this, we first used two-photon calcium imaging to classify the population responses of tectal cells to bars moving at different speeds and in different directions. Subsequently, we performed in-vivo whole cell electrophysiology on these direction selective tectal neurons and we found that their inhibitory inputs were strongly biased towards the null direction of motion, whereas the excitatory inputs showed little selectivity. In addition, we found that excitatory currents evoked by a stimulus moving in the preferred direction occurred before the inhibitory currents whereas a stimulus moving in the null direction evoked currents in the reverse temporal order. The membrane potential modulations resulting from these currents were enhanced by the spike generation mechanism to generate amplified direction selectivity in the spike output. Thus our results implicate a local inhibitory circuit in generating direction selectivity in tectal neurons.

  9. Selective mining of bedded uranium deposits using high-pressure waterjet equipment

    International Nuclear Information System (INIS)

    O'Hanlon, T.A.

    1981-01-01

    High-pressure waterjet equipment is now technically and economically viable and commercially available for the following mining and construction applications: (1) drilling soft to medium-hard rock; (2) slotting, discing, chambering, and reaming in all types of rock. However, additional field experience is needed to prepare detailed economic evaluations. Extensive development of new explosives techniques and blasting methods will be required to take full advantage of the unique waterjet hole slotting, discing, and chambering capabilities

  10. Local selection in the presence of high levels of gene flow: Evidence of heterogeneous insecticide selection pressure across Ugandan Culex quinquefasciatus populations.

    Science.gov (United States)

    Silva Martins, Walter Fabricio; Wilding, Craig Stephen; Steen, Keith; Mawejje, Henry; Antão, Tiago Rodrigues; Donnelly, Martin James

    2017-10-01

    Culex quinquefasciatus collected in Uganda, where no vector control interventions directly targeting this species have been conducted, was used as a model to determine if it is possible to detect heterogeneities in selection pressure driven by insecticide application targeting other insect species. Population genetic structure was assessed through microsatellite analysis, and the impact of insecticide pressure by genotyping two target-site mutations, Vgsc-1014F of the voltage-gated sodium channel target of pyrethroid and DDT insecticides, and Ace1-119S of the acetylcholinesterase gene, target of carbamate and organophosphate insecticides. No significant differences in genetic diversity were observed among populations by microsatellite markers with HE ranging from 0.597 to 0.612 and low, but significant, genetic differentiation among populations (FST = 0.019, P = 0.001). By contrast, the insecticide-resistance markers display heterogeneous allelic distributions with significant differences detected between Central Ugandan (urban) populations relative to Eastern and Southwestern (rural) populations. In the central region, a frequency of 62% for Vgsc-1014F, and 32% for the Ace1-119S resistant allele were observed. Conversely, in both Eastern and Southwestern regions the Vgsc-1014F alleles were close to fixation, whilst Ace1-119S allele frequency was 12% (although frequencies may be underestimated due to copy number variation at both loci). Taken together, the microsatellite and both insecticide resistance target-site markers provide evidence that in the face of intense gene flow among populations, disjunction in resistance frequencies arise due to intense local selection pressures despite an absence of insecticidal control interventions targeting Culex.

  11. Analysis of selective androgen receptor modulators by gas chromatography-microchip atmospheric pressure photoionization-mass spectrometry.

    Science.gov (United States)

    Luosujärvi, Laura; Haapala, Markus; Thevis, Mario; Saarela, Ville; Franssila, Sami; Ketola, Raimo A; Kostiainen, Risto; Kotiaho, Tapio

    2010-02-01

    A gas chromatography-microchip atmospheric pressure photoionization-mass spectrometric (GC-microAPPI-MS) method was developed and used for the analysis of three 2-quinolinone-derived selective androgen receptor modulators (SARMs). SARMs were analyzed from spiked urine samples, which were hydrolyzed and derivatized with N-methyl-N-(trimethylsilyl)trifluoroacetamide before analysis. Trimethylsilyl derivatives of SARMs formed both radical cations (M(+*)) and protonated molecules ([M + H](+)) in photoionization. Better signal-to-noise ratios (S/N) were obtained in MS/MS analysis using the M(+*) ions as precursor ions than using the [M + H](+) ions, and therefore the M(+*) ions were selected for the precursor ions in selected reaction monitoring (SRM) analysis. Limits of detection (LODs) with the method ranged from 0.01 to 1 ng/mL, which correspond to instrumental LODs of 0.2-20 pg. Limits of quantitation ranged from 0.03 to 3 ng/mL. The mass spectrometric response to the analytes was linear (R > or = 0.995) from the LOQ concentration level up to 100 ng/mL concentration, and intra-day repeatabilities were 5%-9%. In addition to the GC-microAPPI-MS study, the proof-of-principle of gas chromatography-microchip atmospheric pressure chemical ionization-Orbitrap MS (GC-microAPCI-Orbitrap MS) was demonstrated. 2010 American Society for Mass Spectrometry. Published by Elsevier Inc. All rights reserved.

  12. Static pressure accelerates ox-LDL-induced cholesterol accumulation via SREBP-1-mediated caveolin-1 downregulation in cultured vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Di-xian, E-mail: luodixian_2@163.com [Department of Pharmacology, School of Pharmaceutics, Central South University, Changsha 410083, Hunan (China); Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); First People' s Hospital of Chenzhou City, Chenzhou 423000, Hunan (China); Xia, Cheng-lai [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Department of Pharmacy, Third Affiliated Hospital Medical College of Guangzhou, Guangzhou 510150, Guangdong (China); Li, Jun-mu [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Xiong, Yan [Department of Pharmacology, School of Pharmaceutics, Central South University, Changsha 410083, Hunan (China); Yuan, Hao-yu [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Lusong Center for Disease Control and Prevention, Zhuzhou 412000, Hunan (China); TANG, Zhen-Wang; Zeng, Yixin [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Liao, Duan-fang, E-mail: dfliao66@yahoo.com.cn [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Department of Traditional Chinese Diagnostics, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 420108, Hunan (China)

    2010-12-03

    Research highlights: {yields} Vertical static pressure accelerates ox-LDL-induced cholesterol accumulation in cultured vascular smooth muscle cells. {yields} Static pressure induces SREBP-1 activation. {yields} Static pressure downregulates the expressions of caveolin-1 by activating SREBP-1. {yields} Static pressure also downregulates the transcription of ABCA1 by activating SREBP-1. {yields} Static pressure increases ox-LDL-induced cholesterol accumulation by SREBP-1-mediated caveolin-1 downregulation in vascular smooth muscle cells cultured in vitro. -- Abstract: Objective: To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism. Methods: Rat-derived VSMC cell line A10 treated with 50 mg/L ox-LDL and different static pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure. Results: Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 {+-} 2.8 mg/g, 31.8 {+-} 0.7 mg/g, 92.3 {+-} 2.1 mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 {+-} 9.4 mg/g, 235.9 {+-} 3.0 mg/g, 386.7 {+-} 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels were

  13. Static pressure accelerates ox-LDL-induced cholesterol accumulation via SREBP-1-mediated caveolin-1 downregulation in cultured vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Luo, Di-xian; Xia, Cheng-lai; Li, Jun-mu; Xiong, Yan; Yuan, Hao-yu; TANG, Zhen-Wang; Zeng, Yixin; Liao, Duan-fang

    2010-01-01

    Research highlights: → Vertical static pressure accelerates ox-LDL-induced cholesterol accumulation in cultured vascular smooth muscle cells. → Static pressure induces SREBP-1 activation. → Static pressure downregulates the expressions of caveolin-1 by activating SREBP-1. → Static pressure also downregulates the transcription of ABCA1 by activating SREBP-1. → Static pressure increases ox-LDL-induced cholesterol accumulation by SREBP-1-mediated caveolin-1 downregulation in vascular smooth muscle cells cultured in vitro. -- Abstract: Objective: To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism. Methods: Rat-derived VSMC cell line A10 treated with 50 mg/L ox-LDL and different static pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure. Results: Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 ± 2.8 mg/g, 31.8 ± 0.7 mg/g, 92.3 ± 2.1 mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 ± 9.4 mg/g, 235.9 ± 3.0 mg/g, 386.7 ± 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels were upregulated. Conclusion: Static

  14. Selective Area Band Engineering of Graphene using Cobalt-Mediated Oxidation.

    Science.gov (United States)

    Bazylewski, Paul F; Nguyen, Van Luan; Bauer, Robert P C; Hunt, Adrian H; McDermott, Eamon J G; Leedahl, Brett D; Kukharenko, Andrey I; Cholakh, Seif O; Kurmaev, Ernst Z; Blaha, Peter; Moewes, Alexander; Lee, Young Hee; Chang, Gap Soo

    2015-10-21

    This study reports a scalable and economical method to open a band gap in single layer graphene by deposition of cobalt metal on its surface using physical vapor deposition in high vacuum. At low cobalt thickness, clusters form at impurity sites on the graphene without etching or damaging the graphene. When exposed to oxygen at room temperature, oxygen functional groups form in proportion to the cobalt thickness that modify the graphene band structure. Cobalt/Graphene resulting from this treatment can support a band gap of 0.30 eV, while remaining largely undamaged to preserve its structural and electrical properties. A mechanism of cobalt-mediated band opening is proposed as a two-step process starting with charge transfer from metal to graphene, followed by formation of oxides where cobalt has been deposited. Contributions from the formation of both CoO and oxygen functional groups on graphene affect the electronic structure to open a band gap. This study demonstrates that cobalt-mediated oxidation is a viable method to introduce a band gap into graphene at room temperature that could be applicable in electronics applications.

  15. Selective Area Band Engineering of Graphene using Cobalt-Mediated Oxidation

    Science.gov (United States)

    Bazylewski, Paul F.; Nguyen, Van Luan; Bauer, Robert P.C.; Hunt, Adrian H.; McDermott, Eamon J. G.; Leedahl, Brett D.; Kukharenko, Andrey I.; Cholakh, Seif O.; Kurmaev, Ernst Z.; Blaha, Peter; Moewes, Alexander; Lee, Young Hee; Chang, Gap Soo

    2015-01-01

    This study reports a scalable and economical method to open a band gap in single layer graphene by deposition of cobalt metal on its surface using physical vapor deposition in high vacuum. At low cobalt thickness, clusters form at impurity sites on the graphene without etching or damaging the graphene. When exposed to oxygen at room temperature, oxygen functional groups form in proportion to the cobalt thickness that modify the graphene band structure. Cobalt/Graphene resulting from this treatment can support a band gap of 0.30 eV, while remaining largely undamaged to preserve its structural and electrical properties. A mechanism of cobalt-mediated band opening is proposed as a two-step process starting with charge transfer from metal to graphene, followed by formation of oxides where cobalt has been deposited. Contributions from the formation of both CoO and oxygen functional groups on graphene affect the electronic structure to open a band gap. This study demonstrates that cobalt-mediated oxidation is a viable method to introduce a band gap into graphene at room temperature that could be applicable in electronics applications. PMID:26486966

  16. Selective killing of ovarian cancer cells through induction of apoptosis by nonequilibrium atmospheric pressure plasma

    International Nuclear Information System (INIS)

    Iseki, Sachiko; Tanaka, Hiromasa; Kondo, Hiroki; Hori, Masaru; Nakamura, Kae; Hayashi, Moemi; Kajiyama, Hiroaki; Kikkawa, Fumitaka; Kano, Hiroyuki

    2012-01-01

    Two independent ovarian cancer cell lines and fibroblast controls were treated with nonequilibrium atmospheric pressure plasma (NEAPP). Most ovarian cancer cells were detached from the culture dish by continuous plasma treatment to a single spot on the dish. Next, the plasma source was applied over the whole dish using a robot arm. In vitro cell proliferation assays showed that plasma treatments significantly decreased proliferation rates of ovarian cancer cells compared to fibroblast cells. Flow cytometry and western blot analysis showed that plasma treatment of ovarian cancer cells induced apoptosis. NEAPP could be a promising tool for therapy for ovarian cancers.

  17. The effect of co-cultivation and selection parameters on Agrobacterium-mediated transformation of Chinese soybean varieties.

    Science.gov (United States)

    Liu, Sheng-Jun; Wei, Zhi-Ming; Huang, Jian-Qiu

    2008-03-01

    In the present study, an efficient Agrobacterium-mediated gene transformation system was developed for soybean [Glycine max (L.) Merrill] based on the examinations of several factors affecting plant transformation efficiency. Increased transformation efficiencies were obtained when the soybean cotyledonary node were inoculated with the Agrobacterium inoculum added with 0.02% (v/v) surfactant (Silwet L-77). The applications of Silwet L-77 (0.02%) during infection and L-cysteine (600 mg l(-1)) during co-cultivation resulted in more significantly improved transformation efficiency than each of the two factors alone. The optimized temperature for infected explant co-cultivation was 22 degrees C. Regenerated transgenic shoots were selected and produced more efficiently with the modified selection scheme (initiation on shoot induction medium without hygromycin for 7 days, with 3 mg l(-1) hygromycin for 10 days, 5 mg l(-1) hygromycin for another 10 days, and elongation on shoot elongation medium with 8 mg l(-1) hygromycin). Using the optimized system, we obtained 145 morphologically normal and fertile independent transgenic plants in five important Chinese soybean varieties. The transformation efficacies ranged from 3.8 to 11.7%. Stable integration, expression and inheritance of the transgenes were confirmed by molecular and genetic analysis. T(1) plants were analyzed and transmission of transgenes to the T(1 )generation in a Mendelian fashion was verified. This optimized transformation system should be employed for efficient Agrobacterium-mediated soybean gene transformation.

  18. Relaxation of herbivore-mediated selection drives the evolution of genetic covariances between plant competitive and defense traits.

    Science.gov (United States)

    Uesugi, Akane; Connallon, Tim; Kessler, André; Monro, Keyne

    2017-06-01

    Insect herbivores are important mediators of selection on traits that impact plant defense against herbivory and competitive ability. Although recent experiments demonstrate a central role for herbivory in driving rapid evolution of defense and competition-mediating traits, whether and how herbivory shapes heritable variation in these traits remains poorly understood. Here, we evaluate the structure and evolutionary stability of the G matrix for plant metabolites that are involved in defense and allelopathy in the tall goldenrod, Solidago altissima. We show that G has evolutionarily diverged between experimentally replicated populations that evolved in the presence versus the absence of ambient herbivory, providing direct evidence for the evolution of G by natural selection. Specifically, evolution in an herbivore-free habitat altered the orientation of G, revealing a negative genetic covariation between defense- and competition-related metabolites that is typically masked in herbivore-exposed populations. Our results may be explained by predictions of classical quantitative genetic theory, as well as the theory of acquisition-allocation trade-offs. The study provides compelling evidence that herbivory drives the evolution of plant genetic architecture. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  19. Endomorphins potentiate acid-sensing ion channel currents and enhance the lactic acid-mediated increase in arterial blood pressure: effects amplified in hindlimb ischaemia.

    Science.gov (United States)

    Farrag, Mohamed; Drobish, Julie K; Puhl, Henry L; Kim, Joyce S; Herold, Paul B; Kaufman, Marc P; Ruiz-Velasco, Victor

    2017-12-01

    Chronic limb ischaemia, characterized by inflammatory mediator release and a low extracellular pH, leads to acid-sensing ion channel (ASIC) activation and reflexively increases mean arterial pressure; endomorphin release is also increased under inflammatory conditions. We examined the modulation of ASIC currents by endomorphins in sensory neurons from rats with freely perfused and ligated femoral arteries: peripheral artery disease (PAD) model. Endomorphins potentiated sustained ASIC currents in both groups of dorsal root ganglion neurons, independent of mu opioid receptor stimulation or G protein activation. Intra-arterial administration of lactic acid (to simulate exercising muscle and evoke a pressor reflex), endomorphin-2 and naloxone resulted in a significantly greater pressor response than lactic acid alone, while administration of APETx2 inhibited endomorphin's enhancing effect in both groups. These results suggest a novel role for endomorphins in modulating ASIC function to effect lactic acid-mediated reflex increase in arterial pressure in patients with PAD. Chronic muscle ischaemia leads to accumulation of lactic acid and other inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in pH and evoke a pressor reflex known to increase mean arterial pressure. The naturally occurring endomorphins are also released by primary afferents under ischaemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex. In rat dorsal root ganglion (DRG) neurons, exposure to E-2 in acidic solutions significantly potentiated ASIC currents when compared to acidic solutions alone. The potentiation was significantly greater in DRG neurons isolated from rats whose femoral arteries were ligated for 72 h. Sustained ASIC current potentiation was also observed

  20. Novel selective phosphodiesterase type 1 inhibitors cause vasodilatation and lower blood pressure in rats

    DEFF Research Database (Denmark)

    Laursen, Morten; Thinggaard, Lilliana Beck; Kehler, Jan

    2017-01-01

    BACKGROUND AND PURPOSE: The PDE enzymes (PDE1-11) hydrolyse and thus inactivate cyclic nucleotides and are important in the regulation of the cardiovascular system. Here,we have investigated the effects on the cardiovascular system, of two novel selective PDE1 inhibitors, Lu AF41228 and Lu AF5802...

  1. The trouble with sliding windows and the selective pressure in BRCA1.

    Directory of Open Access Journals (Sweden)

    Karl Schmid

    Full Text Available Sliding-window analysis has widely been used to uncover synonymous (silent, d(S and nonsynonymous (replacement, d(N rate variation along the protein sequence and to detect regions of a protein under selective constraint (indicated by d(Nd(S. The approach compares two or more protein-coding genes and plots estimates d(/\\(S and d(/\\(N from each sliding window along the sequence. Here we demonstrate that the approach produces artifactual trends of synonymous and nonsynonymous rate variation, with greater variation in d(/\\(S than in d(/\\(N. Such trends are generated even if the true d(S and d(N are constant along the whole protein and different codons are evolving independently. Many published tests of negative and positive selection using sliding windows that we have examined appear to be invalid because they fail to correct for multiple testing. Instead, likelihood ratio tests provide a more rigorous framework for detecting signals of natural selection affecting protein evolution. We demonstrate that a previous finding that a particular region of the BRCA1 gene experienced a synonymous rate reduction driven by purifying selection is likely an artifact of the sliding window analysis. We evaluate various sliding-window analyses in molecular evolution, population genetics, and comparative genomics, and argue that the approach is not generally valid if it is not known a priori that a trend exists and if no correction for multiple testing is applied.

  2. Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution.

    Directory of Open Access Journals (Sweden)

    Matteo Fumagalli

    2011-11-01

    Full Text Available Previous genome-wide scans of positive natural selection in humans have identified a number of non-neutrally evolving genes that play important roles in skin pigmentation, metabolism, or immune function. Recent studies have also shown that a genome-wide pattern of local adaptation can be detected by identifying correlations between patterns of allele frequencies and environmental variables. Despite these observations, the degree to which natural selection is primarily driven by adaptation to local environments, and the role of pathogens or other ecological factors as selective agents, is still under debate. To address this issue, we correlated the spatial allele frequency distribution of a large sample of SNPs from 55 distinct human populations to a set of environmental factors that describe local geographical features such as climate, diet regimes, and pathogen loads. In concordance with previous studies, we detected a significant enrichment of genic SNPs, and particularly non-synonymous SNPs associated with local adaptation. Furthermore, we show that the diversity of the local pathogenic environment is the predominant driver of local adaptation, and that climate, at least as measured here, only plays a relatively minor role. While background demography by far makes the strongest contribution in explaining the genetic variance among populations, we detected about 100 genes which show an unexpectedly strong correlation between allele frequencies and pathogenic environment, after correcting for demography. Conversely, for diet regimes and climatic conditions, no genes show a similar correlation between the environmental factor and allele frequencies. This result is validated using low-coverage sequencing data for multiple populations. Among the loci targeted by pathogen-driven selection, we found an enrichment of genes associated to autoimmune diseases, such as celiac disease, type 1 diabetes, and multiples sclerosis, which lends credence to the

  3. Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution.

    Science.gov (United States)

    Fumagalli, Matteo; Sironi, Manuela; Pozzoli, Uberto; Ferrer-Admetlla, Anna; Ferrer-Admettla, Anna; Pattini, Linda; Nielsen, Rasmus

    2011-11-01

    Previous genome-wide scans of positive natural selection in humans have identified a number of non-neutrally evolving genes that play important roles in skin pigmentation, metabolism, or immune function. Recent studies have also shown that a genome-wide pattern of local adaptation can be detected by identifying correlations between patterns of allele frequencies and environmental variables. Despite these observations, the degree to which natural selection is primarily driven by adaptation to local environments, and the role of pathogens or other ecological factors as selective agents, is still under debate. To address this issue, we correlated the spatial allele frequency distribution of a large sample of SNPs from 55 distinct human populations to a set of environmental factors that describe local geographical features such as climate, diet regimes, and pathogen loads. In concordance with previous studies, we detected a significant enrichment of genic SNPs, and particularly non-synonymous SNPs associated with local adaptation. Furthermore, we show that the diversity of the local pathogenic environment is the predominant driver of local adaptation, and that climate, at least as measured here, only plays a relatively minor role. While background demography by far makes the strongest contribution in explaining the genetic variance among populations, we detected about 100 genes which show an unexpectedly strong correlation between allele frequencies and pathogenic environment, after correcting for demography. Conversely, for diet regimes and climatic conditions, no genes show a similar correlation between the environmental factor and allele frequencies. This result is validated using low-coverage sequencing data for multiple populations. Among the loci targeted by pathogen-driven selection, we found an enrichment of genes associated to autoimmune diseases, such as celiac disease, type 1 diabetes, and multiples sclerosis, which lends credence to the hypothesis that some

  4. Effort-reward imbalance at work and 5-year changes in blood pressure: the mediating effect of changes in body mass index among 1400 white-collar workers.

    Science.gov (United States)

    Trudel, Xavier; Brisson, Chantal; Milot, Alain; Masse, Benoit; Vézina, Michel

    2016-11-01

    A number of prospective studies have documented the effect of adverse psychosocial work factors (work stress) on high blood pressure (BP). Weight gain could be an important pathway by which work stress exerts its effect on BP. No previous prospective study has examined this mediating effect. The aim of the present study was to examine the mediating effect of body mass index (BMI) in the association between psychosocial work factors from Siegrist's effort-reward imbalance model (ERI) and ambulatory BP (ABP). A prospective study was conducted among 1436 white-collar workers. Data were collected three times during a 5-year period. ERI was measured using validated scales, at each time. BMI was measured by a trained assistant. ABP was measured every 15 min during a working day. ERI exposure onset over 3 years was indirectly associated with ABP changes (0.49 mmHg; 95 % CI 0.05, 1.22), through BMI changes, in women with baseline BMI ≥25 kg/m 2 . An effect of similar magnitude and of borderline significance was observed for ERI chronic exposure. No mediating effect was observed among men, and using ERI exposure over 5 years. The mediating effect of BMI was of small magnitude and observed in certain subgroups and time frame only. Subgroup-specific mediating pathways might be involved to explain the effect of work stress on cardiovascular diseases risk.

  5. Predator mediated selection and the impact of developmental stage on viability in wood frog tadpoles (Rana sylvatica

    Directory of Open Access Journals (Sweden)

    Calsbeek Ryan

    2011-12-01

    Full Text Available Abstract Background Complex life histories require adaptation of a single organism for multiple ecological niches. Transitions between life stages, however, may expose individuals to an increased risk of mortality, as the process of metamorphosis typically includes developmental stages that function relatively poorly in both the pre- and post-metamorphic habitat. We studied predator-mediated selection on tadpoles of the wood frog, Rana sylvatica, to identify this hypothesized period of differential predation risk and estimate its ontogenetic onset. We reared tadpoles in replicated mesocosms in the presence of the larval odonate Anax junius, a known tadpole predator. Results The probability of tadpole survival increased with increasing age and size, but declined steeply at the point in development where hind limbs began to erupt from the body wall. Selection gradient analyses indicate that natural selection favored tadpoles with short, deep tail fins. Tadpoles resorb their tails as they progress toward metamorphosis, which may have led to the observed decrease in survivorship. Path models revealed that selection acted directly on tail morphology, rather than through its indirect influence on swimming performance. Conclusions This is consistent with the hypothesis that tail morphology influences predation rates by reducing the probability a predator strikes the head or body.

  6. Mediation in Different Areas of Chinese Legal Reality – Parametrisation of Selected Terminology

    Directory of Open Access Journals (Sweden)

    Grzybek Joanna

    2016-06-01

    Full Text Available The paper deals with terminological issues in legal translation. The author has researched the process of establishing equivalents for partially equivalent terminology, using the parametrical approach to legal translation. The research consists of the terminological analysis of the texts of mediation regulations formulated in Chinese and Polish. The objective was to establish translational equivalents in the case of significant differences between the legal systems of the above mentioned linguistic area. The research was financed from the research grant no. 2012/07/E/HS2/00678, titled: Parameterisation of legilinguistic translatology in the scope of civil law and civil procedure awarded by the National Science Centre of the Republic of Poland (Sonata Bis program.

  7. Antibiotic-mediated selection of quorum-sensing-negative Staphylococcus aureus

    DEFF Research Database (Denmark)

    Paulander, Wilhelm Erik Axel; Varming, Anders Nissen; Bæk, Kristoffer Torbjørn

    2012-01-01

    -acquired S. aureus infections and suggest that the adaptability of S. aureus to antibiotics involves the agr locus. IMPORTANCE: Staphylococcus aureus is the most frequently isolated pathogen in intensive care units and a common cause of nosocomial infections, resulting in a high degree of morbidity......Staphylococcus aureus is a human commensal that at times turns into a serious bacterial pathogen causing life-threatening infections. For the delicate control of virulence, S. aureus employs the agr quorum-sensing system that, via the intracellular effector molecule RNAIII, regulates virulence gene...... increases the agr-mediated fitness cost by inducing the expression of RNAIII. Thus, the extensive use of antibiotics in hospitals may explain why agr-negative variants are frequently isolated from hospital-acquired S. aureus infections but rarely found among community-acquired S. aureus strains. Importantly...

  8. Positive selection pressure introduces secondary mutations at Gag cleavage sites in human immunodeficiency virus type 1 harboring major protease resistance mutations

    DEFF Research Database (Denmark)

    Banke, S.; Lillemark, M.R.; Gerstoft, J.

    2009-01-01

    mutations). Additional sequences from 13 patients were included for longitudinal analysis. We assessed positive selection pressure on the gag/protease region using a test for the overall influence of positive selection and a total of five tests to identify positively selected single codons. We found...... that positive selection pressure was the driving evolutionary force for the gag region in all three patient groups. An increase in positive selection was observed in gag cleavage site regions p7/p1/p6 only after the acquisition of major PI mutations, suggesting that amino acids in gag cleavage sites under...... positive selection pressure could function as compensatory mutations for major PI mutations in the protease region. Isolated gag mutations did not appear to confer PI resistance, but mutations in the gag cleavage sites could substitute for minor PI resistance mutations in the protease region Udgivelsesdato...

  9. Selective exposure, political polarization, and possible mediators: Evidence from the Netherlands

    NARCIS (Netherlands)

    Trilling, D.; van Klingeren, M.; Tsfati, Y.

    2017-01-01

    One of the main lines of reasoning in the contemporary debate on media effects is the notion that selective exposure to congruent information can lead to political polarization. Most studies are correlational, potentially plagued with self-report biases, and cannot demonstrate time order. Even less

  10. Selective Exposure, Political Polarization, and Possible Mediators: Evidence From the Netherlands

    NARCIS (Netherlands)

    Trilling, D.C.; Klingeren, M. van; Tsfati, Y.

    2017-01-01

    One of the main lines of reasoning in the contemporary debate on media effects is the notion that selective exposure to congruent information can lead to political polarization. Most studies are correlational, potentially plagued with self-report biases, and cannot demonstrate time order. Even less

  11. Highly selective nitroxyl radical-mediated oxidation of primary alcohol groups in water-soluble glucans

    NARCIS (Netherlands)

    Nooy, A.E.J. de; Besemer, A.C.; Bekkum, H. van

    1995-01-01

    With catalytic amounts of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) and hypochlorite/bromide as the regenerating oxidant in water, primary alcohol groups in glucans and derivatives thereof were rapidly and completely oxidised. For pyranosides, selectivity was higher than 95% and no side products

  12. Parasite-mediated selection drives an immunogenetic tradeoff in plains zebra (Equus quagga)

    Science.gov (United States)

    Kamath, Pauline L.; Turner, Wendy C.; Küsters, Martina; Getz, Wayne M.

    2014-01-01

    Pathogen evasion of the host immune system is a key force driving extreme polymorphism in genes of the major histocompatibility complex (MHC). Although this gene family is well characterized in structure and function, there is still much debate surrounding the mechanisms by which MHC diversity is selectively maintained. Many studies have investigated relationships between MHC variation and specific pathogens, and have found mixed support for and against the hypotheses of heterozygote advantage, frequency-dependent or fluctuating selection. Few, however, have focused on the selective effects of multiple parasite types on host immunogenetic patterns. Here, we examined relationships between variation in the equine MHC gene, ELA-DRA, and both gastrointestinal (GI) and ectoparasitism in plains zebras (Equus quagga). Specific alleles present at opposing population frequencies had antagonistic effects, with rare alleles associated with increased GI parasitism and common alleles with increased tick burdens. These results support a frequency-dependent mechanism, but are also consistent with fluctuating selection. Maladaptive GI parasite ‘susceptibility alleles’ were reduced in frequency, suggesting that these parasites may play a greater selective role at this locus. Heterozygote advantage, in terms of allele mutational divergence, also predicted decreased GI parasite burden in genotypes with a common allele. We conclude that an immunogenetic trade-off affects resistance/susceptibility to parasites in this system. Because GI and ectoparasites do not directly interact within hosts, our results uniquely show that antagonistic parasite interactions can be indirectly modulated through the host immune system. This study highlights the importance of investigating the role of multiple parasites in shaping patterns of host immunogenetic variation.

  13. Parasite-mediated selection drives an immunogenetic trade-off in plains zebras (Equus quagga).

    Science.gov (United States)

    Kamath, Pauline L; Turner, Wendy C; Küsters, Martina; Getz, Wayne M

    2014-05-22

    Pathogen evasion of the host immune system is a key force driving extreme polymorphism in genes of the major histocompatibility complex (MHC). Although this gene family is well characterized in structure and function, there is still much debate surrounding the mechanisms by which MHC diversity is selectively maintained. Many studies have investigated relationships between MHC variation and specific pathogens, and have found mixed support for and against the hypotheses of heterozygote advantage, frequency-dependent or fluctuating selection. Few, however, have focused on the selective effects of multiple parasite types on host immunogenetic patterns. Here, we examined relationships between variation in the equine MHC gene, ELA-DRA, and both gastrointestinal (GI) and ectoparasitism in plains zebras (Equus quagga). Specific alleles present at opposing population frequencies had antagonistic effects, with rare alleles associated with increased GI parasitism and common alleles with increased tick burdens. These results support a frequency-dependent mechanism, but are also consistent with fluctuating selection. Maladaptive GI parasite 'susceptibility alleles' were reduced in frequency, suggesting that these parasites may play a greater selective role at this locus. Heterozygote advantage, in terms of allele mutational divergence, also predicted decreased GI parasite burden in genotypes with a common allele. We conclude that an immunogenetic trade-off affects resistance/susceptibility to parasites in this system. Because GI and ectoparasites do not directly interact within hosts, our results uniquely show that antagonistic parasite interactions can be indirectly modulated through the host immune system. This study highlights the importance of investigating the role of multiple parasites in shaping patterns of host immunogenetic variation.

  14. Microporous organic polymers involving thiadiazolopyridine for high and selective uptake of greenhouse gases at low pressure.

    Science.gov (United States)

    Waseem Hussain, M D; Bandyopadhyay, Sujoy; Patra, Abhijit

    2017-09-21

    A new core of [1,2,5]-thiadiazolo-[3,4-c]-pyridine was employed for the fabrication of microporous organic polymers exhibiting a very high CO 2 uptake of 5.8 mmol g -1 (25.5 wt%) at 273 K and 1 bar. The presence of CO 2 -philic active sites and microporosity confer the high uptake and superior selectivity (61) towards CO 2 over N 2 .

  15. Germline amino acid diversity in B cell receptors is a good predictor of somatic selection pressures.

    Directory of Open Access Journals (Sweden)

    Gregory Warren Schwartz

    2013-11-01

    Full Text Available The diversity of the immune repertoire is important for the adaptive immunesystem's ability to detect pathogens. Much of this diversity is generated in twosteps, first through the recombination of germline gene segments and secondthrough hypermutation during an immune response. While both steps are to someextent based on the germline level repertoire of genes, the final structure andselection of specific receptors is at the somatic level. How germline diversityand selection relate to somatic diversity and selection has not been clear.To investigate how germline diversity relates to somatic diversityand selection, we considered the published repertoire of Ig heavy chain Vgenes taken from the blood of 12 individuals, post-vaccination againstinfluenza, sequenced by 454 high-throughput sequencing. We here show that whenwe consider individual amino acid positions in the heavy chain V gene sequence,there exists a strong correlation between the diversity of the germlinerepertoire at a position and the number of B cell clones that change amino acidat that position. At the same time, we find that the diversity of amino acidsused in the mutated positions is greater than in the germline, albeit stillcorrelated to germline diversity. From these findings, we proposethat while germline diversity and germline amino acid usage at a givenposition do not fully specify the amino acid mutant needed to promotesurvival of specific clones, germline diversity at a given position is agood indicator for the potential to survive after somatic mutation at thatposition. We would therefore suggest that germline diversity at eachspecific position is the better a priori model for the effects of somaticmutation and selection, than simply the division into complementaritydetermining and framework regions.

  16. Tear production, intraocular pressure and conjunctival bacterial flora in selected captive wild ruminants.

    Science.gov (United States)

    Kvapil, Pavel; Pirš, Tina; Slavec, Brigita; Luštrik, Roman; Zemljič, Tadej; Bártová, Eva; Stranjac, Bojana; Kastelic, Marjan

    2018-01-01

    Evaluation of tear production (Schirmer's tear test, STT) and measurement of intraocular pressure (IOP) were performed in a population of captive wild ungulates in a Slovenian ZOO during routine annual health check. In total, 10 fallow deer (Dama dama), 25 mouflons (Ovis aries musimon), 20 alpine ibexes (Capra ibex), and three alpine chamois (Rupicapra rupicapra) were included in the study. Tear production was performed by Schirmer's tear test, IOP was measured with an applanation tonometer, and ophthalmological examination was conducted with slit-lamp biomicroscopy and indirect ophthalmoscopy. Conjunctival swabs were taken and submitted for aerobic bacteriology and for detection of Chlamydia spp. and Mycoplasma spp. tested by PCR. Average tear production (in mm/min) was 17.8 ± 3.16 for fallow deer, 17.9 ± 3.87 for mouflons, and 11.7 ± 3.87 for ibexes. Mean intraocular pressure (IOP, in mm Hg) was 14.1 ± 2.48 for fallow deer, 14.9 ± 2.20 for mouflons, and 13.1 ± 2.43 for ibexes. For chamois, average tear production and IOP were 14.5 ± 3.0 and 10.2 ± 2.5, respectively; this is the first record of STT I and IOP in chamois. Bacteriological swabs were positive for bacteria in 100% of the fallow deer, 56% of mouflons, 35% of ibexes, and 100% of chamois. Gram-positive bacteria were predominant. Moraxella spp., Chlamydia spp., and Mycoplasma spp. were not detected. The reported values were obtained in animals under manual restraint only to be applicative in similar conditions. © 2017 American College of Veterinary Ophthalmologists.

  17. Probing of RNA structures in a positive sense RNA virus reveals selection pressures for structural elements

    Science.gov (United States)

    Watters, Kyle E; Choudhary, Krishna; Aviran, Sharon; Perry, Keith L

    2018-01-01

    Abstract In single stranded (+)-sense RNA viruses, RNA structural elements (SEs) play essential roles in the infection process from replication to encapsidation. Using selective 2′-hydroxyl acylation analyzed by primer extension sequencing (SHAPE-Seq) and covariation analysis, we explore the structural features of the third genome segment of cucumber mosaic virus (CMV), RNA3 (2216 nt), both in vitro and in plant cell lysates. Comparing SHAPE-Seq and covariation analysis results revealed multiple SEs in the coat protein open reading frame and 3′ untranslated region. Four of these SEs were mutated and serially passaged in Nicotiana tabacum plants to identify biologically selected changes to the original mutated sequences. After passaging, loop mutants showed partial reversion to their wild-type sequence and SEs that were structurally disrupted by mutations were restored to wild-type-like structures via synonymous mutations in planta. These results support the existence and selection of virus open reading frame SEs in the host organism and provide a framework for further studies on the role of RNA structure in viral infection. Additionally, this work demonstrates the applicability of high-throughput chemical probing in plant cell lysates and presents a new method for calculating SHAPE reactivities from overlapping reverse transcriptase priming sites. PMID:29294088

  18. Pseudoliquid behavior of heteropoly compound catalysts. Unusual pressure dependencies of the rate and selectivity for ethanol dehydration

    International Nuclear Information System (INIS)

    Misono, M.; Okuhara, T.; Ichiki, T.; Arai, T.; Kanda, Y.

    1987-01-01

    Heteropoly compounds arenow utilized as industrial catalysts for olefin hydration and aldehyde oxidation and as interesting cluster models of mixed oxide catalysts. Certain heteropoly acids, like H 3 PW 12 O 40 and H 3 PMo 12 O 40 , easily absorb a large amount of water, alchols, and ethers in the solid state, although their surface areas are very low. This is not adsorption in micropores; rather molecules are absorbed between the lattice polyanions, sometimes expanding the lattice. The expansion can be seen visually as well as by x-ray diffraction. The authors showed that in some cases catalytic reactions take place in this novel bulk phase. Presumably due to this behavior, very high catalytic activity and unique selectivity as well as unusual reactivity order have been observed. They called this state the pseudoliquid phase. However, in only one case was the amount of absorbed reactant measured under the working conditions. They report here unusual pressure dependencies of the rate and selectivity of ethanol dehydration over heteropoly compounds. The dependency can only be explained by the formation of a pseudoliquid phase, i.e., a phase where the amount of absorbed ethanol has changed as a function of ethanol pressure

  19. Selective pressurized liquid extraction for the analysis of polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins and dibenzofurans in soil.

    Science.gov (United States)

    Klees, Marcel; Bogatzki, Corinna; Hiester, Ernst

    2016-10-14

    During this study a high throughout selective pressurized liquid extraction (SPLE) method was developed and validated for the simultaneous extraction of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/PCDFs) and polychlorinated biphenyls (PCBs) from soil. To that end, extraction rates of PCBs from soil utilizing different extraction solvents and different extraction temperatures were investigated whereas extraction rates were comparable for toluene, n-hexane and dichloromethane (extraction conditions for all utilized solvents: 33mL PLE extraction cell, extraction temperature: 110°C, static extraction time: 5min, flush volume: 60%, purge 90s). Ratios of native PCBs and PCDD/PCDFs congener concentrations after Soxhlet and selective pressurized liquid extraction (SPLE) showed that SPLE is an alternative sample preparation step for the simultaneous determination of PCDD/PCDFs and PCBs in soil. Additional clean-up steps for the separation of PCBs and PCDD/PCDFs utilizing alumina were performed in order to avoid interferences between the component classes. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Fusion of Selected Cells and Vesicles Mediated by Optically Trapped Plasmonic Nanoparticles

    DEFF Research Database (Denmark)

    Bahadori, Azra

    . In this work, we introduce a novel and extremely flexible physical method which can trigger membrane fusion in a highly selective manner not only between synthetic GUVs of different compositions, but also between live cells which remain viable after fusion. Optical tweezers’ laser (1064 nm) is used to position......Selective fusion of two membrane surrounded volumes is of great interest in nanochemistry and nanomedicine as it can pave the way for performing controlled nanoscale chemical reactions and for delivering a cargo (e.g., chemicals, genetic regulatory factors, etc.) to a desired living cell...... the two desired cells and/or GUVs next to each other and in immediate contact. Then, the same laser is placed in the contact zone between the two adjacent membranes until one or more gold nanoparticles diffuse into the focus. Gold nanoparticles absorb part of near infrared light and dissipate the absorbed...

  1. Spontaneous Phase Transfer-Mediated Selective Removal of Heavy Metal Ions Using Biocompatible Oleic Acid.

    Science.gov (United States)

    Chang, Jeehan; Yoo, Sooyeon; Lee, Wooju; Kim, Dongchoul; Kang, Taewook

    2017-12-01

    Here, we propose an environmentally benign removal technique for heavy metal ions based on selective and spontaneous transfer to oleic acid. The ions can be removed via (1) the selective and rapid complexation with the carboxylic end of oleic acid at an oleic acid/water interface, and (2) the diffusion of such complex into the oleic acid layer. A wide variety of heavy metal ions such as Cu 2+ , Pb 2+ , Zn 2+ , and Ni 2+ can be selectively removed over K + and Na + . For example, the concentration of Cu 2+ is reduced to below 1.3 ppm within 24 h, which corresponds to the level of Cu 2+ permitted by the Environmental Protection Agency. The addition of ethylenediamine ligand to the metal ion solutions is also shown to enhance the phase transfer. The removal efficiency is increased by up to 6 times when compared with that in the absence of the ligand and follows the order, Cu 2+ (99%) > Pb 2+ (96%) > Zn 2+ (95%) > Ni 2+ (65%). Moreover, the removal time can be shortened from 24 h to 1 h. The effect of an emulsion induced by a mechanical agitation on the removal of heavy metal ion is also studied.

  2. Smoothed Bootstrap Aggregation for Assessing Selection Pressure at Amino Acid Sites.

    Science.gov (United States)

    Mingrone, Joseph; Susko, Edward; Bielawski, Joseph

    2016-11-01

    To detect positive selection at individual amino acid sites, most methods use an empirical Bayes approach. After parameters of a Markov process of codon evolution are estimated via maximum likelihood, they are passed to Bayes formula to compute the posterior probability that a site evolved under positive selection. A difficulty with this approach is that parameter estimates with large errors can negatively impact Bayesian classification. By assigning priors to some parameters, Bayes Empirical Bayes (BEB) mitigates this problem. However, as implemented, it imposes uniform priors, which causes it to be overly conservative in some cases. When standard regularity conditions are not met and parameter estimates are unstable, inference, even under BEB, can be negatively impacted. We present an alternative to BEB called smoothed bootstrap aggregation (SBA), which bootstraps site patterns from an alignment of protein coding DNA sequences to accommodate the uncertainty in the parameter estimates. We show that deriving the correction for parameter uncertainty from the data in hand, in combination with kernel smoothing techniques, improves site specific inference of positive selection. We compare BEB to SBA by simulation and real data analysis. Simulation results show that SBA balances accuracy and power at least as well as BEB, and when parameter estimates are unstable, the performance gap between BEB and SBA can widen in favor of SBA. SBA is applicable to a wide variety of other inference problems in molecular evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Photo-mediated ultrasound therapy (PUT): a novel method of selectively treating neovascularization (Conference Presentation)

    Science.gov (United States)

    Zhang, Haonan; Hu, Zi Zhong; Li, Jia; Mordovanakis, Aghapi G.; Yang, Xinmai; Paulus, Yannis M.; Wang, Xueding

    2017-02-01

    Retinal and choroidal neovascularization play a pivotal role in the leading causes of blindness including macular degeneration and diabetic retinopathy (DR). Current therapy by focal laser photocoagulation can damage the normal surrounding cells, such as the photoreceptor inner and outer segments which are adjacent to the retinal pigment epithelium (RPE), due to the use of high laser energy and millisecond pulse duration. Therapies with pharmaceutical agents involve systemic administration of drugs, which can cause adverse effects and patients may become drug-resistant. We have developed a noninvasive photo-mediated ultrasound therapy (PUT) technique as a localized antivascular method, and applied it to remove micro blood vessels in the retina. PUT takes advantage of the high native optical contrast among biological tissues, and has the unique capability to self-target microvessels without causing unwanted damages to the surrounding tissues. This technique promotes cavitation activity in blood vessels by synergistically applying nanosecond laser pulses and ultrasound bursts. Through the interaction between cavitation and blood vessel wall, blood clots in microvessels and vasoconstriction can be induced. As a result, microvessels can be occluded. In comparison with other techniques that involves cavitation, both laser and ultrasound energy needed in PUT is significantly lower, and hence improves the safety in therapy.

  4. Beyond Neuronal Activity Markers: Select Immediate Early Genes in Striatal Neuron Subtypes Functionally Mediate Psychostimulant Addiction

    Directory of Open Access Journals (Sweden)

    Ramesh Chandra

    2017-06-01

    Full Text Available Immediate early genes (IEGs were traditionally used as markers of neuronal activity in striatum in response to stimuli including drugs of abuse such as psychostimulants. Early studies using these neuronal activity markers led to important insights in striatal neuron subtype responsiveness to psychostimulants. Such studies have helped identify striatum as a critical brain center for motivational, reinforcement and habitual behaviors in psychostimulant addiction. While the use of IEGs as neuronal activity markers in response to psychostimulants and other stimuli persists today, the functional role and implications of these IEGs has often been neglected. Nonetheless, there is a subset of research that investigates the functional role of IEGs in molecular, cellular and behavioral alterations by psychostimulants through striatal medium spiny neuron (MSN subtypes, the two projection neuron subtypes in striatum. This review article will address and highlight the studies that provide a functional mechanism by which IEGs mediate psychostimulant molecular, cellular and behavioral plasticity through MSN subtypes. Insight into the functional role of IEGs in striatal MSN subtypes could provide improved understanding into addiction and neuropsychiatric diseases affecting striatum, such as affective disorders and compulsive disorders characterized by dysfunctional motivation and habitual behavior.

  5. A review of selected school-based conflict resolution and peer mediation projects.

    Science.gov (United States)

    Powell, K E; Muir-McClain, L; Halasyamani, L

    1995-12-01

    Many U.S. schools are implementing curricula and other activities to reduce interpersonal violence among students. Most involve conflict resolution or peer mediation (CR/PM) training. Little is known about the effectiveness or manner of implementing these projects. This paper examines nine projects supported by four state health departments. Available data suggest some projects may modify youths' self-reported attitudes about violent behavior, improve school discipline, and reduce absenteeism. The review also revealed considerable variation in implementation, especially in the role of professionally trained consultants and amount of teacher and student training. More attention should be paid to evaluating CR/PM projects. Some data suggest they may contribute positively to community efforts to reduce violence among youth, but insufficient information exists to know which projects best serve which students, and how projects should be implemented. Until consensus emerges, project personnel should carefully assess the implementation and impact of their activities. Routinely collected data, such as disciplinary actions, can be used for evaluation, often with only minor modification.

  6. Xilei San Ameliorates Experimental Colitis in Rats by Selectively Degrading Proinflammatory Mediators and Promoting Mucosal Repair

    Directory of Open Access Journals (Sweden)

    Yongbiao Hao

    2014-01-01

    Full Text Available Xilei san (XLS, a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC. The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS to the rats’ drinking water for 7 days. XLS was administered daily by retention enema from day 2 to day 7; the rats were sacrificed on day 8. The colon tissues were obtained for further experiments. A histological damage score and the activity of tissue myeloperoxidase were used to evaluate the severity of the colitis. The colonic cytokine levels were detected in a suspension array, and epithelial proliferation was assessed using Ki-67 immunohistochemistry. Intrarectal administration of XLS attenuated the DSS-induced colitis, as evidenced by a reduction in both the histological damage score and myeloperoxidase activity. It also decreased the levels of proinflammatory cytokines, but increased the mucosal repair-related cytokines. In addition, the epithelial Ki-67 expression was upregulated by XLS. These results suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory mediators and promoting mucosal repair. XLS could be a potential topical treatment for human UC.

  7. Genetics of the DST-mediated mRNA decay pathway using a transgene-based selection.

    Science.gov (United States)

    Lidder, P; Johnson, M A; Sullivan, M L; Thompson, D M; Pérez-Amador, M A; Howard, C J; Green, P J

    2004-08-01

    mRNA sequences that control abundance, localization and translation initiation have been identified, yet the factors that recognize these sequences are largely unknown. In this report, a transgene-based strategy designed to isolate mutants of Arabidopsis thaliana that fail to recognize these sequences is described. In this strategy, a selectable gene and a screenable marker gene are put under the control of the sequence element being analysed and mutants are selected with altered abundance of the corresponding marker RNAs. The selection of mutants deficient in recognition of the DST (downstream) mRNA degradation signal is used as a test-case to illustrate some of the technical aspects that have facilitated success. Using this strategy, we report the isolation of a new mutant, dst3, deficient in the DST-mediated mRNA decay pathway. The targeted genetic strategy described circumvents certain technical limitations of biochemical approaches. Hence, it provides a means to investigate a variety of other mechanisms responsible for post-transcriptional regulation.

  8. Wavelength-selective and diffuse infrared thermal emission mediated by magnetic polaritons from silicon carbide metasurfaces

    Science.gov (United States)

    Yang, Yue; Taylor, Sydney; Alshehri, Hassan; Wang, Liping

    2017-07-01

    In the present study, we experimentally demonstrate the spectrally coherent and diffuse thermal emission by exciting magnetic polaritons in SiC metasurfaces fabricated by the focused ion beam technique. Spectral emittance characterized by using an infrared microscope coupled to a Fourier transform spectrometer clearly shows a wavelength-selective emission peak as high as 0.8. Numerical simulations including emittance spectra and contour plot of electromagnetic field distribution were carried out to verify and understand the underlying mechanism of magnetic polaritons. The metasurfaces were further shown to be direction and polarization independent. The results would facilitate metasurfaces for applications like radiative thermal management and infrared sensing.

  9. Alkoxy-auxins are selective inhibitors of auxin transport mediated by PIN, ABCB, and AUX1 transporters.

    Science.gov (United States)

    Tsuda, Etsuko; Yang, Haibing; Nishimura, Takeshi; Uehara, Yukiko; Sakai, Tatsuya; Furutani, Masahiko; Koshiba, Tomokazu; Hirose, Masakazu; Nozaki, Hiroshi; Murphy, Angus S; Hayashi, Ken-ichiro

    2011-01-21

    Polar auxin movement is a primary regulator of programmed and plastic plant development. Auxin transport is highly regulated at the cellular level and is mediated by coordinated transport activity of plasma membrane-localized PIN, ABCB, and AUX1/LAX transporters. The activity of these transporters has been extensively analyzed using a combination of pharmacological inhibitors, synthetic auxins, and knock-out mutants in Arabidopsis. However, efforts to analyze auxin-dependent growth in other species that are less tractable to genetic manipulation require more selective inhibitors than are currently available. In this report, we characterize the inhibitory activity of 5-alkoxy derivatives of indole 3-acetic acid and 7-alkoxy derivatives of naphthalene 1-acetic acid, finding that the hexyloxy and benzyloxy derivatives act as potent inhibitors of auxin action in plants. These alkoxy-auxin analogs inhibit polar auxin transport and tropic responses associated with asymmetric auxin distribution in Arabidopsis and maize. The alkoxy-auxin analogs inhibit auxin transport mediated by AUX1, PIN, and ABCB proteins expressed in yeast. However, these analogs did not inhibit or activate SCF(TIR1) auxin signaling and had no effect on the subcellular trafficking of PIN proteins. Together these results indicate that alkoxy-auxins are inactive auxin analogs for auxin signaling, but are recognized by PIN, ABCB, and AUX1 auxin transport proteins. Alkoxy-auxins are powerful new tools for analyses of auxin-dependent development.

  10. Alkoxy-auxins Are Selective Inhibitors of Auxin Transport Mediated by PIN, ABCB, and AUX1 Transporters*

    Science.gov (United States)

    Tsuda, Etsuko; Yang, Haibing; Nishimura, Takeshi; Uehara, Yukiko; Sakai, Tatsuya; Furutani, Masahiko; Koshiba, Tomokazu; Hirose, Masakazu; Nozaki, Hiroshi; Murphy, Angus S.; Hayashi, Ken-ichiro

    2011-01-01

    Polar auxin movement is a primary regulator of programmed and plastic plant development. Auxin transport is highly regulated at the cellular level and is mediated by coordinated transport activity of plasma membrane-localized PIN, ABCB, and AUX1/LAX transporters. The activity of these transporters has been extensively analyzed using a combination of pharmacological inhibitors, synthetic auxins, and knock-out mutants in Arabidopsis. However, efforts to analyze auxin-dependent growth in other species that are less tractable to genetic manipulation require more selective inhibitors than are currently available. In this report, we characterize the inhibitory activity of 5-alkoxy derivatives of indole 3-acetic acid and 7-alkoxy derivatives of naphthalene 1-acetic acid, finding that the hexyloxy and benzyloxy derivatives act as potent inhibitors of auxin action in plants. These alkoxy-auxin analogs inhibit polar auxin transport and tropic responses associated with asymmetric auxin distribution in Arabidopsis and maize. The alkoxy-auxin analogs inhibit auxin transport mediated by AUX1, PIN, and ABCB proteins expressed in yeast. However, these analogs did not inhibit or activate SCFTIR1 auxin signaling and had no effect on the subcellular trafficking of PIN proteins. Together these results indicate that alkoxy-auxins are inactive auxin analogs for auxin signaling, but are recognized by PIN, ABCB, and AUX1 auxin transport proteins. Alkoxy-auxins are powerful new tools for analyses of auxin-dependent development. PMID:21084292

  11. Oviposition site-selection by Bactrocera dorsalis is mediated through an innate recognition template tuned to γ-octalactone.

    Directory of Open Access Journals (Sweden)

    Kamala Jayanthi Pagadala Damodaram

    Full Text Available Innate recognition templates (IRTs in insects are developed through many years of evolution. Here we investigated olfactory cues mediating oviposition behavior in the oriental fruit fly, Bactrocera dorsalis, and their role in triggering an IRT for oviposition site recognition. Behavioral assays with electrophysiologically active compounds from a preferred host, mango, revealed that one of the volatiles tested, γ-octalactone, had a powerful effect in eliciting oviposition by gravid B. dorsalis females. Electrophysiological responses were obtained and flies clearly differentiated between treated and untreated substrates over a wide range of concentrations of γ-octalactone. It triggered an innate response in flies, overriding inputs from other modalities required for oviposition site evaluation. A complex blend of mango volatiles not containing γ-octalactone elicited low levels of oviposition, whereas γ-octalactone alone elicited more oviposition response. Naïve flies with different rearing histories showed similar responses to γ-octalactone. Taken together, these results indicate that oviposition site selection in B. dorsalis is mediated through an IRT tuned to γ-octalactone. Our study provides empirical data on a cue underpinning innate behavior and may also find use in control operations against this invasive horticultural pest.

  12. Selective alpha-particle mediated depletion of tumor vasculature with vascular normalization.

    Directory of Open Access Journals (Sweden)

    Jaspreet Singh Jaggi

    2007-03-01

    Full Text Available Abnormal regulation of angiogenesis in tumors results in the formation of vessels that are necessary for tumor growth, but compromised in structure and function. Abnormal tumor vasculature impairs oxygen and drug delivery and results in radiotherapy and chemotherapy resistance, respectively. Alpha particles are extraordinarily potent, short-ranged radiations with geometry uniquely suitable for selectively killing neovasculature.Actinium-225 ((225Ac-E4G10, an alpha-emitting antibody construct reactive with the unengaged form of vascular endothelial cadherin, is capable of potent, selective killing of tumor neovascular endothelium and late endothelial progenitors in bone-marrow and blood. No specific normal-tissue uptake of E4G10 was seen by imaging or post-mortem biodistribution studies in mice. In a mouse-model of prostatic carcinoma, (225Ac-E4G10 treatment resulted in inhibition of tumor growth, lower serum prostate specific antigen level and markedly prolonged survival, which was further enhanced by subsequent administration of paclitaxel. Immunohistochemistry revealed lower vessel density and enhanced tumor cell apoptosis in (225Ac-E4G10 treated tumors. Additionally, the residual tumor vasculature appeared normalized as evident by enhanced pericyte coverage following (225Ac-E4G10 therapy. However, no toxicity was observed in vascularized normal organs following (225Ac-E4G10 therapy.The data suggest that alpha-particle immunotherapy to neovasculature, alone or in combination with sequential chemotherapy, is an effective approach to cancer therapy.

  13. Outer-selective pressure-retarded osmosis hollow fiber membranes from vacuum-assisted interfacial polymerization for osmotic power generation

    KAUST Repository

    Sun, Shipeng

    2013-11-19

    In this paper, we report the technical breakthroughs to synthesize outer-selective thin-film composite (TFC) hollow fiber membranes, which is in an urgent need for osmotic power generation with the pressure-retarded osmosis (PRO) process. In the first step, a defect-free thin-film composite membrane module is achieved by vacuum-assisted interfacial polymerization. The PRO performance is further enhanced by optimizing the support in terms of pore size and mechanical strength and the TFC layer with polydopamine coating and molecular engineering of the interfacial polymerization solution. The newly developed membranes can stand over 20 bar with a peak power density of 7.63 W/m2, which is equivalent to 13.72 W/m2 of its inner-selective hollow fiber counterpart with the same module size, packing density, and fiber dimensions. The study may provide insightful guidelines for optimizing the interfacial polymerization procedures and scaling up of the outer-selective TFC hollow fiber membrane modules for PRO power generation. © 2013 American Chemical Society.

  14. Outer-selective pressure-retarded osmosis hollow fiber membranes from vacuum-assisted interfacial polymerization for osmotic power generation.

    Science.gov (United States)

    Sun, Shi-Peng; Chung, Tai-Shung

    2013-11-19

    In this paper, we report the technical breakthroughs to synthesize outer-selective thin-film composite (TFC) hollow fiber membranes, which is in an urgent need for osmotic power generation with the pressure-retarded osmosis (PRO) process. In the first step, a defect-free thin-film composite membrane module is achieved by vacuum-assisted interfacial polymerization. The PRO performance is further enhanced by optimizing the support in terms of pore size and mechanical strength and the TFC layer with polydopamine coating and molecular engineering of the interfacial polymerization solution. The newly developed membranes can stand over 20 bar with a peak power density of 7.63 W/m(2), which is equivalent to 13.72 W/m(2) of its inner-selective hollow fiber counterpart with the same module size, packing density, and fiber dimensions. The study may provide insightful guidelines for optimizing the interfacial polymerization procedures and scaling up of the outer-selective TFC hollow fiber membrane modules for PRO power generation.

  15. A lover or a fighter? Opposing sexual selection pressures on men’s vocal pitch and facial hair

    Science.gov (United States)

    Mackey, Lauren L.; McCarty, Kristofor; Neave, Nick

    2016-01-01

    The traditional assumption within the research literature on human sexually dimorphic traits has been that many sex differences have arisen from intersexual selection. More recently, however, there has been a shift toward the idea that many male features, including male lower-pitched voices and male beard growth, might have arisen predominantly through intrasexual selection: that is, to serve the purpose of male–male competition instead of mate attraction. In this study, using a unique set of video stimuli, we measured people’s perceptions of the dominance and attractiveness of men who differ both in terms of voice pitch (4 levels from lower to higher pitched) and beard growth (4 levels from clean shaven to a month’s hair growth). We found a nonlinear relationship between lower pitch and increased attractiveness; men’s vocal attractiveness peaked at around 96 Hz. Beard growth had equivocal effects on attractiveness judgments. In contrast, perceptions of men’s dominance simply increased with increasing masculinity (i.e., with lower-pitched voices and greater beard growth). Together, these results suggest that the optimal level of physical masculinity might differ depending on whether the outcome is social dominance or mate attraction. These dual selection pressures might maintain some of the documented variability in male physical and behavioral masculinity that we see today. PMID:27004013

  16. Using Bourdieu in Critical Mediatization Research: Communicational Doxa and Osmotic Pressures in the Field of UN Organizations

    Directory of Open Access Journals (Sweden)

    André Jansson

    2015-05-01

    Full Text Available This article develops a Bourdieusian approach to mediatization. It is argued that the Bourdieusian theories of doxa and fields can make valuable contributions to a critical perspective on mediatization, one that moves beyond the divides between institutionalist, social-constructivist and materialist understandings (e.g., Bourdieu, 1972/1977. Mediatization is here seen as the historically growing dependence on media technologies and institutions within diverse social fields and settings. In order to establish the link between mediatization and Bourdieu’s theories (ibid., the article introduces the concept of communicational doxa, which refers to the taken for granted communicational conventions and demands that regulate the inclusion of membership within a particular field. The article also shows how communicational doxa can be applied as an analytical concept. Findings from qualitative fieldwork carried out among highly mobile and skilled professionals within the field of UN organizations in Geneva, show how the autonomy of social agents is negotiated in relation to an increasingly mediatized communicational doxa.

  17. Fitness Cost of Daptomycin-Resistant Staphylococcus aureus Obtained from in Vitro Daptomycin Selection Pressure

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    Shuguang Li

    2017-11-01

    Full Text Available Daptomycin-resistant (DAP-R Staphylococcus aureus strains are well documented, but have not been reported in China. To elucidate the evolution adaptability and fitness cost of DAP-R S. aureus, three DAP susceptible strains, Pre3 (MRSA, ST239-t037, Pre5 (MRSA, ST239-t037, and Pre14b (MSSA, ST188-t189, were isolated from patients with bloodstream infections, and serially passaged in Mueller–Hinton broth with a gradient of DAP concentration to select for resistance. Highly DAP-R mutants were obtained after screening for 34 passages. The DAP minimum inhibitory concentrations increased from 0.5 μg/ml in the parent strains to 16 μg/ml in the mutants, which remained tolerant to 4 μg/ml of DAP for more than 160 generations. The growth of the three mutant strains was slower than that of the parent strains, with relative fitness cost of 34.8%, 19.2%, and 15.0%, respectively. The in vitro serum tolerance of the mutants was decreased, and the lethality and pathogenicity in mice were weakened (P < 0.01. Transmission electron microscopy found that the cell walls of the mutants were significantly thicker (from 38.6% to 75.4% than those of the parent cells. Mutation L826F of mprF was found in Post14b, G299V, and L473I of mprF and Y225N of walK were found in Post3, while T345A of mprF, S52N of graS, and F473I of walK were found in Post5. Thus, stable DAP-R mutants could be obtained from a middle-short term of in vitro DAP selection, and according to their fitness cost, some prevention and control work may be done to cope with DAP-R S. aureus that may appear in China in the future.

  18. Attentional selection of levels within hierarchically organized figures is mediated by object-files

    Directory of Open Access Journals (Sweden)

    Mitchell Joseph Valdes-Sosa

    2014-12-01

    Full Text Available Objects frequently have a hierarchical organization (tree-branch-leaf. How do we select the level to be attended? This has been explored with compound letters: a global letter built from local letters. One explanation, backed by much empirical support, is that attentional competition is biased towards certain spatial frequency (SF bands across all locations and objects (a SF filter. This view assumes that the global and local letters are carried respectively by low and high SF bands, and that the bias can persist over time. Here we advocate a complementary view in which perception of hierarchical level is determined by how we represent each object-file. Although many properties bound to an object-file (i.e. position, color, even shape can mutate without affecting its persistence over time, we posit that same object-file cannot be used to store information from different hierarchical levels. Thus selection of level would be independent from locations but not from the way objects are represented at each moment. These views were contrasted via an attentional blink paradigm that presented letters within compound figures, but only one level at a time. Attending to two letters in rapid succession was easier if they were at the same- compared to different-levels, as predicted by both accounts. However, only the object-file account was able to explain why it was easier to report two targets on the same moving object compared to the same targets on distinct objects. The interference of different masks on target recognition was also easier to predict by the object-file account than by the SF filter. The methods introduced here allowed us to investigate attention to hierarchical levels and to objects within the same empirical framework. The data suggests that SF information is used to structure the internal organization of object representations, a process understood best by integrating object-file theory with previous models of hierarchical perception.

  19. Viral vector-mediated selective and reversible blockade of the pathway for visual orienting in mice

    Directory of Open Access Journals (Sweden)

    Tadashi eIsa

    2013-10-01

    Full Text Available Recently, by using a combination of two viral vectors, we developed a technique for pathway-selective and reversible synaptic transmission blockade, and successfully induced a behavioral deficit of dexterous hand movements in macaque monkeys by affecting a population of spinal interneurons. To explore the capacity of this technique to work in other pathways and species, and to obtain fundamental methodological information, we tried to block the crossed tecto-reticular pathway, which is known to control orienting responses to visual targets, in mice. A neuron-specific retrograde gene transfer vector with the gene encoding enhanced tetanus neurotoxin (eTeNT tagged with enhanced green fluorescent protein (EGFP under the control of a tetracycline responsive element was injected into the left medial pontine reticular formation. 7–17 days later, an adeno-associated viral vector with a highly efficient Tet-ON sequence, rtTAV16, was injected into the right superior colliculus. 5–9 weeks later, the daily administration of doxycycline (Dox was initiated. Visual orienting responses toward the left side were impaired 1 - 4 days after Dox administration. Anti-GFP immunohistochemistry revealed that a number of neurons in the intermediate and deep layers of the right superior colliculus were positively stained, indicating eTeNT expression. After the termination of Dox administration, the anti-GFP staining returned to the baseline level within 28 days. A second round of Dox administration, starting from 28 days after the termination of the first Dox administration, resulted in the reappearance of the behavioral impairment. These findings showed that pathway-selective and reversible blockade of synaptic transmission causes behavioral effects also in rodents, and that the crossed tecto-reticular pathway surely controls visual orienting behaviors.

  20. Overexpression of the neuronal human (pro)renin receptor mediates angiotensin II-independent blood pressure regulation in the central nervous system.

    Science.gov (United States)

    Peng, Hua; Jensen, Dane D; Li, Wencheng; Sullivan, Michelle N; Buller, Sophie A; Worker, Caleb J; Cooper, Silvana G; Zheng, Shiqi; Earley, Scott; Sigmund, Curt D; Feng, Yumei

    2018-03-01

    Despite advances in antihypertensive therapeutics, at least 15-20% of hypertensive patients have resistant hypertension through mechanisms that remain poorly understood. In this study, we provide a new mechanism for the regulation of blood pressure (BP) in the central nervous system (CNS) by the (pro)renin receptor (PRR), a recently identified component of the renin-angiotensin system that mediates ANG II formation in the CNS. Although PRR also mediates ANG II-independent signaling, the importance of these pathways in BP regulation is unknown. Here, we developed a unique transgenic mouse model overexpressing human PRR (hPRR) specifically in neurons (Syn-hPRR). Intracerebroventricular infusion of human prorenin caused increased BP in Syn-hPRR mice. This BP response was attenuated by a NADPH oxidase (NOX) inhibitor but not by antihypertensive agents that target the renin-angiotensin system. Using a brain-targeted genetic knockdown approach, we found that NOX4 was the key isoform responsible for the prorenin-induced elevation of BP in Syn-hPRR mice. Moreover, inhibition of ERK significantly attenuated the increase in NOX activity and BP induced by human prorenin. Collectively, our findings indicate that an ANG II-independent, PRR-mediated signaling pathway regulates BP in the CNS by a PRR-ERK-NOX4 mechanism. NEW & NOTEWORTHY This study characterizes a new transgenic mouse model with overexpression of the human (pro)renin receptor in neurons and demonstrated a novel angiotensin II-independent mechanism mediated by human prorenin and the (pro)renin receptor in the central regulation of blood pressure.

  1. Migratory Recovery from Infection as a Selective Pressure for the Evolution of Migration.

    Science.gov (United States)

    Shaw, Allison K; Binning, Sandra A

    2016-04-01

    Migration, a widespread animal behavior, can influence how individuals acquire and transmit pathogens. Past work has demonstrated that migration can reduce the costs of pathogen or parasite infection through two processes: migratory escape from infected areas or individuals and migratory culling of infected individuals. Here, we propose a third process: migratory recovery, where infected individuals lose their parasites and recover from infection during migration. Recovery can occur when parasites and/or their intermediate hosts cannot support changes in the migratory host's internal or external environment during migration. Thus, parasite mortality increases with migration. Although migratory recovery is likely widespread across species, it remains challenging to empirically test it as a selective force promoting migration. We develop a model and determine the conditions under which migratory recovery theoretically favors the evolution of migration. We show that incorporating migratory recovery into a model of migratory escape increases the range of biologically realistic conditions favoring migration and leads to scenarios where partial migration can evolve. Motivated by empirical estimates of infection costs, our model shows how recovery from infection could drive the evolution of migration. We suggest a number of future directions for both theoretical and empirical research in this area.

  2. Comparing strategies for selection of low-density SNPs for imputation-mediated genomic prediction in U. S. Holsteins.

    Science.gov (United States)

    He, Jun; Xu, Jiaqi; Wu, Xiao-Lin; Bauck, Stewart; Lee, Jungjae; Morota, Gota; Kachman, Stephen D; Spangler, Matthew L

    2018-04-01

    SNP chips are commonly used for genotyping animals in genomic selection but strategies for selecting low-density (LD) SNPs for imputation-mediated genomic selection have not been addressed adequately. The main purpose of the present study was to compare the performance of eight LD (6K) SNP panels, each selected by a different strategy exploiting a combination of three major factors: evenly-spaced SNPs, increased minor allele frequencies, and SNP-trait associations either for single traits independently or for all the three traits jointly. The imputation accuracies from 6K to 80K SNP genotypes were between 96.2 and 98.2%. Genomic prediction accuracies obtained using imputed 80K genotypes were between 0.817 and 0.821 for daughter pregnancy rate, between 0.838 and 0.844 for fat yield, and between 0.850 and 0.863 for milk yield. The two SNP panels optimized on the three major factors had the highest genomic prediction accuracy (0.821-0.863), and these accuracies were very close to those obtained using observed 80K genotypes (0.825-0.868). Further exploration of the underlying relationships showed that genomic prediction accuracies did not respond linearly to imputation accuracies, but were significantly affected by genotype (imputation) errors of SNPs in association with the traits to be predicted. SNPs optimal for map coverage and MAF were favorable for obtaining accurate imputation of genotypes whereas trait-associated SNPs improved genomic prediction accuracies. Thus, optimal LD SNP panels were the ones that combined both strengths. The present results have practical implications on the design of LD SNP chips for imputation-enabled genomic prediction.

  3. Temporal genetic stability in natural populations of the waterflea Daphnia magna in response to strong selection pressure.

    Science.gov (United States)

    Orsini, Luisa; Marshall, Hollie; Cuenca Cambronero, Maria; Chaturvedi, Anurag; Thomas, Kelley W; Pfrender, Michael E; Spanier, Katina I; De Meester, Luc

    2016-12-01

    Studies monitoring changes in genetic diversity and composition through time allow a unique understanding of evolutionary dynamics and persistence of natural populations. However, such studies are often limited to species with short generation times that can be propagated in the laboratory or few exceptional cases in the wild. Species that produce dormant stages provide powerful models for the reconstruction of evolutionary dynamics in the natural environment. A remaining open question is to what extent dormant egg banks are an unbiased representation of populations and hence of the species' evolutionary potential, especially in the presence of strong environmental selection. We address this key question using the water flea Daphnia magna, which produces dormant stages that accumulate in biological archives over time. We assess temporal genetic stability in three biological archives, previously used in resurrection ecology studies showing adaptive evolutionary responses to rapid environmental change. We show that neutral genetic diversity does not decline with the age of the population and it is maintained in the presence of strong selection. In addition, by comparing temporal genetic stability in hatched and unhatched populations from the same biological archive, we show that dormant egg banks can be consulted to obtain a reliable measure of genetic diversity over time, at least in the multidecadal time frame studied here. The stability of neutral genetic diversity through time is likely mediated by the buffering effect of the resting egg bank. © 2016 John Wiley & Sons Ltd.

  4. Identification of learning and memory genes in canine; promoter investigation and determining the selective pressure.

    Science.gov (United States)

    Seifi Moroudi, Reihane; Masoudi, Ali Akbar; Vaez Torshizi, Rasoul; Zandi, Mohammad

    2014-12-01

    One of the important behaviors of dogs is trainability which is affected by learning and memory genes. These kinds of the genes have not yet been identified in dogs. In the current research, these genes were found in animal models by mining the biological data and scientific literatures. The proteins of these genes were obtained from the UniProt database in dogs and humans. Not all homologous proteins perform similar functions, thus comparison of these proteins was studied in terms of protein families, domains, biological processes, molecular functions, and cellular location of metabolic pathways in Interpro, KEGG, Quick Go and Psort databases. The results showed that some of these proteins have the same performance in the rat or mouse, dog, and human. It is anticipated that the protein of these genes may be effective in learning and memory in dogs. Then, the expression pattern of the recognized genes was investigated in the dog hippocampus using the existing information in the GEO profile. The results showed that BDNF, TAC1 and CCK genes are expressed in the dog hippocampus, therefore, these genes could be strong candidates associated with learning and memory in dogs. Subsequently, due to the importance of the promoter regions in gene function, this region was investigated in the above genes. Analysis of the promoter indicated that the HNF-4 site of BDNF gene and the transcription start site of CCK gene is exposed to methylation. Phylogenetic analysis of protein sequences of these genes showed high similarity in each of these three genes among the studied species. The dN/dS ratio for BDNF, TAC1 and CCK genes indicates a purifying selection during the evolution of the genes.

  5. Influence of feeding pattern and hydraulic selection pressure to control filamentous bulking in biological treatment of dairy wastewaters.

    Science.gov (United States)

    Meunier, Christophe; Henriet, Olivier; Schoonbroodt, Bastien; Boeur, Jean-Marc; Mahillon, Jacques; Henry, Paul

    2016-12-01

    In sequencing batch reactors (SBRs) treating dairy wastewaters, the overgrowth of filamentous bacteria is a frequent cause of operational problems. The present study aimed at understanding to what extent the operating conditions of a SBR can be optimized to convert a bulking activated sludge into a well-settling biomass at low aeration velocity. The abundance of filament morphotypes and floc-formers able to store biopolymers were analysed by PCR-DGGE and 16S amplicon sequencing. The results indicated that a combination of an anaerobic-microaerated feeding pattern with a low selective pressure was beneficial to supress filamentous overgrowth and to form aerobic granules, while increasing the efficiency of suspended solid removal. Average removal efficiencies for total chemical oxygen demand (COD), total nitrogen (TN) and total phosphorus (TP) were 94±2%, 95±1% and 83±13%, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Optimization of selective area growth of GaAs by low pressure organometallic vapor phase epitaxy for monolithic integrated circuits

    Science.gov (United States)

    Kanber, H.; Bar, S. X.; Norris, P. E.; Beckham, C.; Pacer, M.

    1994-02-01

    GaAs MESFET device structures have been grown on silicon nitride or silicon dioxide masked 50 and 76 mm GaAs substrates by low pressure organometallic vapor phase epitaxy. Very smooth, featureless morphology and 100 percent selectivity of GaAs islands have been achieved over a range of growth conditions. Optimization of the GaAs p-buffer of the field effect transistor structure has led to improved device performance, including increased breakdown voltage. Device characteristics of the 0.5 μm gate low noise metal semiconductor field-effect transistors fabricated on these islands show good performance and wafer to wafer reproducibility on the second device lot.

  7. Oxygen Vacancy-Mediated Photocatalysis of BiOCl: Reactivity, Selectivity, and Perspectives.

    Science.gov (United States)

    Li, Hao; Li, Jie; Ai, Zhihui; Jia, Falong; Zhang, Lizhi

    2018-01-02

    Semiconductor photocatalysis is a trustworthy approach to harvest clean solar light for energy conversions, while state-of-the-art catalytic efficiencies are unsatisfactory because of the finite light response and/or recombination of robust charge carriers. Along with the development of modern material characterization techniques and electronic-structure computations, oxygen vacancies (OVs) on the surface of real photocatalysts, even in infinitesimal concentration, are found to play a more decisive role in determining the kinetics, energetics, and mechanisms of photocatalytic reactions. This Review endeavors to clarify the inherent functionality of OVs in photocatalysis at the surface molecular level using 2D BiOCl as the platform. Structure sensitivity of OVs on reactivity and selectivity of photocatalytic reactions is intensely discussed via confining OVs onto prototypical BiOCl surfaces of different structures. The critical understanding of OVs chemistry can help consolidate and advance the fundamental theories of photocatalysis, and also offer new perspectives and guidelines for the rational design of catalysts with satisfactory performance. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Sorting nexin 5 selectively regulates dorsal-ruffle-mediated macropinocytosis in primary macrophages.

    Science.gov (United States)

    Lim, Jet Phey; Gosavi, Prajakta; Mintern, Justine D; Ross, Ellen M; Gleeson, Paul A

    2015-12-01

    The regulation of macropinocytosis, a specialised endocytosis pathway, is important for immune cell function. However, it is not known whether the biogenesis of macropinosomes involves one or more distinct pathways. We previously identified sorting nexin 5 (SNX5) as a regulator of macropinocytosis in macrophages. Here, we show that bone-marrow-derived macrophages from SNX5-knockout mice had a 60-70% reduction in macropinocytic uptake of dextran or ovalbumin, whereas phagocytosis and retrograde transport from the plasma membrane to the Golgi was unaffected. In contrast, deficiency of SNX5 had no effect on macropinocytosis or antigen presentation by dendritic cells. Activation of macrophages with CSF-1 resulted in a localisation of SNX5 to actin-rich ruffles in a manner dependent on receptor tyrosine kinases. SNX5-deficient macrophages showed a dramatic reduction in ruffling on the dorsal surface following CSF-1 receptor activation, whereas peripheral ruffling and cell migration were unaffected. We demonstrate that SNX5 is acting upstream of actin polymerisation following CSF-1 receptor activation. Overall, our findings reveal the important contribution of dorsal ruffing to receptor-activated macropinocytosis in primary macrophages and show that SNX5 selectively regulates macropinosomes derived from the dorsal ruffles. © 2015. Published by The Company of Biologists Ltd.

  9. Design and fabrication of inner-selective thin-film composite (TFC) hollow fiber modules for pressure retarded osmosis (PRO)

    KAUST Repository

    Wan, Chun Feng

    2016-08-03

    Pressure retarded osmosis (PRO) is a promising technology to harvest the renewable osmotic energy from salinity gradients. There are great progresses in the fabrication of PRO membranes in the last decade. Thin-film composite (TFC) hollow fibers have been widely studied and demonstrated superior performance. However, the lack of effective TFC hollow fiber modules hinders the commercialization of the PRO technology. Knowledge and experiences to fabricate TFC hollow fiber modules remain limited in the open literature. In this study, we aim to reveal the engineering and science on how to fabricate TFC hollow fiber modules including the formation of inner-selective polyamide layers and the repair of leakages. TFC-PES hollow fiber modules with 30% and 50% packing densities have been successfully fabricated, showing peak power densities of 20.0 W/m2 and 19.4 W/m2, respectively, at 20 bar using 1 M NaCl solution and DI water as feeds. The modules may be damaged during handling and high pressure testing. The repaired modules have a power density of 18.2 W/m2, 91% of the power densities of the undamaged ones. This study would make up the gap between TFC membrane fabrication and TFC membrane module fabrication in the membrane industry. © 2016 Elsevier B.V.

  10. Competition between conjugation and M13 phage infection in Escherichia coli in the absence of selection pressure: a kinetic study.

    Science.gov (United States)

    Wan, Zhenmao; Goddard, Noel L

    2012-10-01

    Inter- and intraspecies horizontal gene transfer enabled by bacterial secretion systems is a powerful mechanism for bacterial genome plasticity. The type IV secretion system of Escherichia coli, encoded by the F plasmid, enables cell-to-cell contact and subsequent DNA transfer known as conjugation. Conjugation is compromised by phage infection that specifically targets the secretion machinery. Hence, the use of phages to regulate the spread of genes, such as acquired antibiotic resistance or as general biosanitation agents, has gained interest. To predict the potential efficacy, the competition kinetics must first be understood. Using quantitative PCR to enumerate genomic loci in a resource-limited batch culture, we quantify the infection kinetics of the nonlytic phage M13 and its impact on conjugation in the absence of selection pressure (isogenic set). Modeling the resulting experimental data reveals the cellular growth rate to be reduced to 60% upon phage infection. We also find a maximum phage infection rate of 3×10(-11) mL phage(-1) min(-1) which is only 1 order of magnitude slower than the maximum conjugation rate (3×10(-10) mL cell(-1) min(-1)), suggesting phages must be in significant abundance to be effective antagonists to horizontal gene transfer. In the regime where the number of susceptible cells (F(+)) and phages are equal upon initial infection, we observe the spread of the conjugative plasmid throughout the cell population despite phage infection, but only at 10% of the uninfected rate. This has interesting evolutionary implications, as even in the absence of selection pressure, cells maintain the ability to conjugate despite phage vulnerability and the associated growth consequences.

  11. Effects of selection pressure and genetic association on the relationship between antibiotic resistance and virulence in Escherichia coli.

    Science.gov (United States)

    Zhang, Lixin; Levy, Karen; Trueba, Gabriel; Cevallos, William; Trostle, James; Foxman, Betsy; Marrs, Carl F; Eisenberg, Joseph N S

    2015-11-01

    Antibiotic selection pressure and genetic associations may lead to the cooccurrence of resistance and virulence in individual pathogens. However, there is a lack of rigorous epidemiological evidence that demonstrates the cooccurrence of resistance and virulence at the population level. Using samples from a population-based case-control study in 25 villages in rural Ecuador, we characterized resistance to 12 antibiotics among pathogenic (n = 86) and commensal (n = 761) Escherichia coli isolates, classified by the presence or absence of known diarrheagenic virulence factor genes. The prevalences of resistance to single and multiple antibiotics were significantly higher for pathogenic isolates than for commensal isolates. Using a generalized estimating equation, antibiotic resistance was independently associated with virulence factor carriage, case status, and antibiotic use (for these respective factors: odds ratio [OR] = 3.0, with a 95% confidence interval [CI] of 1.7 to 5.1; OR = 2.0, with a 95% CI of 1.3 to 3.0; and OR = 1.5, with a 95% CI of 0.9 to 2.5). Virulence factor carriage was more strongly related to antibiotic resistance than antibiotic use for all antibiotics examined, with the exception of fluoroquinolones, gentamicin, and cefotaxime. This study provides epidemiological evidence that antibiotic resistance and virulence factor carriage are linked in E. coli populations in a community setting. Further, these data suggest that while the cooccurrence of resistance and virulence in E. coli is partially due to antibiotic selection pressure, it is also genetically determined. These findings should be considered in developing strategies for treating infections and controlling for antibiotic resistance. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. Effects of Selection Pressure and Genetic Association on the Relationship between Antibiotic Resistance and Virulence in Escherichia coli

    Science.gov (United States)

    Trueba, Gabriel; Cevallos, William; Trostle, James; Marrs, Carl F.; Eisenberg, Joseph N. S.

    2015-01-01

    Antibiotic selection pressure and genetic associations may lead to the cooccurrence of resistance and virulence in individual pathogens. However, there is a lack of rigorous epidemiological evidence that demonstrates the cooccurrence of resistance and virulence at the population level. Using samples from a population-based case-control study in 25 villages in rural Ecuador, we characterized resistance to 12 antibiotics among pathogenic (n = 86) and commensal (n = 761) Escherichia coli isolates, classified by the presence or absence of known diarrheagenic virulence factor genes. The prevalences of resistance to single and multiple antibiotics were significantly higher for pathogenic isolates than for commensal isolates. Using a generalized estimating equation, antibiotic resistance was independently associated with virulence factor carriage, case status, and antibiotic use (for these respective factors: odds ratio [OR] = 3.0, with a 95% confidence interval [CI] of 1.7 to 5.1; OR = 2.0, with a 95% CI of 1.3 to 3.0; and OR = 1.5, with a 95% CI of 0.9 to 2.5). Virulence factor carriage was more strongly related to antibiotic resistance than antibiotic use for all antibiotics examined, with the exception of fluoroquinolones, gentamicin, and cefotaxime. This study provides epidemiological evidence that antibiotic resistance and virulence factor carriage are linked in E. coli populations in a community setting. Further, these data suggest that while the cooccurrence of resistance and virulence in E. coli is partially due to antibiotic selection pressure, it is also genetically determined. These findings should be considered in developing strategies for treating infections and controlling for antibiotic resistance. PMID:26282415

  13. Early Intraocular Pressure Spikes Observed After Selective Laser Trabeculoplasty Treatment and Risk Factors

    Directory of Open Access Journals (Sweden)

    Fırat Helvacıoğlu

    2014-10-01

    Full Text Available Objectives: To analyze the IOP spikes after selective laser trabeculoplasty (SLT. Materials and Methods: Two hundred eyes of 100 patients who applied to the clinic between 01.11.2010 and 31.10.2011 and who had primary SLT treatment with the diagnosis of primary open-angle glaucoma or ocular hypertension were enrolled in the study. Patients’ demographic data, iris color, angle pigmentation, and angle degree measurements with goniolens, pachymetry measurements by optic coherence tomography (OCT, cup/disk measurements (by indirect ophthalmoscopy, and IOP measurements (by applanation tonometry were noted. The relations between iris color, angle pigmentation, pachymetry and total energy with IOP spike and anterior chamber reactions observed at the 1st and 2nd hour of treatment were evaluated. Results: Thirty-seven percent of the patients were male and 63% of the patients were female. The mean age of males and females was 61.24±11.33 (33-85 and 58.21±12.35 (22-80, respectively. Mean IOP spikes and anterior chamber reactions at the 1st and 2nd hour of the treatment were 3.35 and 2.21 mmHg, respectively, and they were positively correlated (p=0.0001. As the eyes were examined according to iris color, statistically significant higher IOP spikes were observed in brown eyes (3.77 mmHg than in green (2.62 mmHg and hazel eyes (1.85 mmHg (p=0.0001. No significant relationship was found between IOP spikes and pachymetry and total energy whereas positive correlation was observed between IOP spikes and angle pigmentation (p1=0.904, p2=0.823, p3=0.0001. Conclusion: IOP spikes seen after SLT treatment were observed more frequently in dark colored eyes or in eyes with heavily pigmented angles. We believe, the follow-up of these patients requires attention. (Turk J Ophthalmol 2014; 44: 365-9

  14. Natural selection acts in opposite ways on correlated hormonal mediators of prenatal maternal effects in a wild bird population.

    Science.gov (United States)

    Tschirren, Barbara; Postma, Erik; Gustafsson, Lars; Groothuis, Ton G G; Doligez, Blandine

    2014-10-01

    Maternal hormones are important mediators of prenatal maternal effects. Although many experimental studies have demonstrated their potency in shaping offspring phenotypes, we know remarkably little about their adaptive value. Using long-term data on a wild collared flycatcher (Ficedula albicollis) population, we show that natural selection acts in opposite ways on two maternally derived androgens, yolk androstenedione (A4) and yolk testosterone (T). High yolk A4 concentrations are associated with higher fitness, whereas high yolk T concentrations are associated with lower fitness. Natural selection thus favours females that produce eggs with high A4 and low T concentrations. Importantly, however, there exists a positive (non-genetic) correlation between A4 and T, which suggests that females are limited in their ability to reach this adaptive optimum. Thereby, these results provide strong evidence for an adaptive value of differential maternal androgen deposition, and a mechanistic explanation for the maintenance of variation in maternal investment in the wild. © 2014 John Wiley & Sons Ltd/CNRS.

  15. Controlled and selective placement of boron subphthalocyanines on either chain end of polymers synthesized by nitroxide mediated polymerization

    Directory of Open Access Journals (Sweden)

    Benoît H. Lessard

    2015-10-01

    Full Text Available In previous studies, we synthesized the first organic light emitting diode (OLED using boron subphthalocyanines (BsubPcs based polymers. When designing new polymer materials for organic electronic applications such as OLEDs or organic photovoltaic (OPV devices it is important to consider not only the contribution of each monomer but also the polymer chain ends. In this paper we establish a post-polymerization strategy to couple BsubPcs onto either the α- or the ω-chain end using chemically selective BsubPc derivatives. We outline how the chain ends of two representative polymers, poly(styrene (PS and poly(n-butylacrylate (BA, synthesized by nitroxide mediated polymerization (NMP, using BlocBuilder-MA as the initiating species, can be chemically modified by the incorporation of BsubPc chromophores. The addition of the BsubPc chromophore was confirmed through the use of a photodiode array detector (PDA connected in-line with a gel permeation chromatography (GPC setup. These findings represent the first reported method for the controlled and selective placement of a BsubPc chromophores on either end of a polymer produced by NMP. This strategy will therefore be utilized to make next generation BsubPc polymers for OLEDs and OPV devices. The extremely high molar extinction coefficient of BsubPc also make these polymers ideally suited for dye-labelling of polymers.

  16. Non-p-glycoprotein-mediated multidrug resistance in detransformed rat cells selected for resistance to methylglyoxal bis(guanylhydrazone).

    Science.gov (United States)

    Weber, J M; Sircar, S; Horvath, J; Dion, P

    1989-11-01

    Three independent variants (G2, G4, G5), resistant to methylglyoxal bis(guanylhydrazone), an anticancer drug, have been isolated by single step selection from an adenovirus-transformed rat brain cell line (1). These variants display selective cross-resistance to several natural product drugs of dissimilar structure and action. Multidrug resistance has recently been shown to be caused by overexpression of the membrane-associated p-glycoprotein, most often caused by amplification of the mdr gene. Several types of experiments were conducted to determine whether the observed drug resistance in our cell lines could be due to changes at the mdr locus. The following results were obtained: (a) the mdr locus was not amplified; (b) transcription of the mdr gene and p-glycoprotein synthesis were not increased; (c) multidrug resistance cell lines, which carry an amplified mdr locus, were not cross-resistant to methylglyoxal bis(guanylhydrazone); (d) verapamil did not reverse the resistance of G cells or mdr cells to methylglyoxal bis(guanylhydrazone), nor that of G cells to vincristine; and (e) methylglyoxal bis(guanylhydrazone) resistance was recessive and depended on a block to drug uptake, as opposed to mdr cells which are dominant and express increased drug efflux. The results obtained suggest that the drug resistance in the G2, G4, and G5 cells was atypical and may be due to a mechanism distinct from that mediated by the mdr locus.

  17. Functionally Selective Signaling for Morphine and Fentanyl Antinociception and Tolerance Mediated by the Rat Periaqueductal Gray

    Science.gov (United States)

    Morgan, Michael M.; Reid, Rachel A.; Saville, Kimber A.

    2014-01-01

    Functionally selective signaling appears to contribute to the variability in mechanisms that underlie tolerance to the antinociceptive effects of opioids. The present study tested this hypothesis by examining the contribution of G protein-coupled receptor kinase (GRK)/Protein kinase C (PKC) and C-Jun N-terminal kinase (JNK) activation on both the expression and development of tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray of the rat. Microinjection of morphine or fentanyl into the periaqueductal gray produced a dose-dependent increase in hot plate latency. Microinjection of the non-specific GRK/PKC inhibitor Ro 32-0432 into the periaqueductal gray to block mu-opioid receptor phosphorylation enhanced the antinociceptive effect of morphine but had no effect on fentanyl antinociception. Microinjection of the JNK inhibitor SP600125 had no effect on morphine or fentanyl antinociception, but blocked the expression of tolerance to repeated morphine microinjections. In contrast, a microinjection of Ro 32-0432 blocked the expression of fentanyl, but not morphine tolerance. Repeated microinjections of Ro 32-0432 blocked the development of morphine tolerance and inhibited fentanyl antinociception whether rats were tolerant or not. Repeated microinjections of SP600125 into the periaqueductal gray blocked the development of tolerance to both morphine and fentanyl microinjections. These data demonstrate that the signaling molecules that contribute to tolerance vary depending on the opioid and methodology used to assess tolerance (expression vs. development of tolerance). This signaling difference is especially clear for the expression of tolerance in which JNK contributes to morphine tolerance and GRK/PKC contributes to fentanyl tolerance. PMID:25503060

  18. Vacuole-mediated selective regulation of TORC1-Sch9 signaling following oxidative stress.

    Science.gov (United States)

    Takeda, Eigo; Jin, Natsuko; Itakura, Eisuke; Kira, Shintaro; Kamada, Yoshiaki; Weisman, Lois S; Noda, Takeshi; Matsuura, Akira

    2018-02-15

    Target of rapamycin complex 1 (TORC1) is a central cellular signaling coordinator that allows eukaryotic cells to adapt to the environment. In the budding yeast, Saccharomyces cerevisiae , TORC1 senses nitrogen and various stressors and modulates proteosynthesis, nitrogen uptake and metabolism, stress responses, and autophagy. There is some indication that TORC1 may regulate these downstream pathways individually. However, the potential mechanisms for such differential regulation are unknown. Here we show that the serine/threonine protein kinase Sch9 branch of TORC1 signaling depends specifically on the integrity of the vacuolar membrane, and this dependency originates in changes in Sch9 localization reflected by phosphatidylinositol 3,5-bisphosphate. Moreover, oxidative stress induces the delocalization of Sch9 from vacuoles, contributing to the persistent inhibition of the Sch9 branch after stress. Thus, our results establish that regulation of the vacuolar localization of Sch9 serves as a selective switch for the Sch9 branch in divergent TORC1 signaling. We propose that the Sch9 branch integrates the intrinsic activity of TORC1 kinase and vacuolar status, which is monitored by the phospholipids of the vacuolar membrane, into the regulation of macromolecular synthesis. © 2018 Takeda et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  19. Reorganization of neural systems mediating peripheral visual selective attention in the deaf: An optical imaging study.

    Science.gov (United States)

    Seymour, Jenessa L; Low, Kathy A; Maclin, Edward L; Chiarelli, Antonio M; Mathewson, Kyle E; Fabiani, Monica; Gratton, Gabriele; Dye, Matthew W G

    2017-01-01

    Theories of brain plasticity propose that, in the absence of input from the preferred sensory modality, some specialized brain areas may be recruited when processing information from other modalities, which may result in improved performance. The Useful Field of View task has previously been used to demonstrate that early deafness positively impacts peripheral visual attention. The current study sought to determine the neural changes associated with those deafness-related enhancements in visual performance. Based on previous findings, we hypothesized that recruitment of posterior portions of Brodmann area 22, a brain region most commonly associated with auditory processing, would be correlated with peripheral selective attention as measured using the Useful Field of View task. We report data from severe to profoundly deaf adults and normal-hearing controls who performed the Useful Field of View task while cortical activity was recorded using the event-related optical signal. Behavioral performance, obtained in a separate session, showed that deaf subjects had lower thresholds (i.e., better performance) on the Useful Field of View task. The event-related optical data indicated greater activity for the deaf adults than for the normal-hearing controls during the task in the posterior portion of Brodmann area 22 in the right hemisphere. Furthermore, the behavioral thresholds correlated significantly with this neural activity. This work provides further support for the hypothesis that cross-modal plasticity in deaf individuals appears in higher-order auditory cortices, whereas no similar evidence was obtained for primary auditory areas. It is also the only neuroimaging study to date that has linked deaf-related changes in the right temporal lobe to visual task performance outside of the imaging environment. The event-related optical signal is a valuable technique for studying cross-modal plasticity in deaf humans. The non-invasive and relatively quiet characteristics of

  20. THE REDSHIFT EVOLUTION OF THE MEAN TEMPERATURE, PRESSURE, AND ENTROPY PROFILES IN 80 SPT-SELECTED GALAXY CLUSTERS

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, M.; Benson, B. A.; Vikhlinin, A.; Aird, K. A.; Allen, S. W.; Bautz, M.; Bayliss, M.; Bleem, L. E.; Bocquet, S.; Brodwin, M.; Carlstrom, J. E.; Chang, C. L.; Cho, H. M.; Clocchiatti, A.; Crawford, T. M.; Crites, A. T.; de Haan, T.; Dobbs, M. A.; Foley, R. J.; Forman, W. R.; George, E. M.; Gladders, M. D.; Gonzalez, A. H.; Halverson, N. W.; Hlavacek-Larrondo, J.; Holder, G. P.; Holzapfel, W. L.; Hrubes, J. D.; Jones, C.; Keisler, R.; Knox, L.; Lee, A. T.; Leitch, E. M.; Liu, J.; Lueker, M.; Luong-Van, D.; Mantz, A.; Marrone, D. P.; McMahon, J. J.; Meyer, S. S.; Miller, E. D.; Mocanu, L.; Mohr, J. J.; Murray, S. S.; Padin, S.; Pryke, C.; Reichardt, C. L.; Rest, A.; Ruhl, J. E.; Saliwanchik, B. R.; Saro, A.; Sayre, J. T.; Schaffer, K. K.; Shirokoff, E.; Spieler, H. G.; Stalder, B.; Stanford, S. A.; Staniszewski, Z.; Stark, A. A.; Story, K. T.; Stubbs, C. W.; Vanderlinde, K.; Vieira, J. D.; Williamson, R.; Zahn, O.; Zenteno, A.

    2014-09-24

    We present the results of an X-ray analysis of 80 galaxy clusters selected in the 2500 deg(2) South Pole Telescope survey and observed with the Chandra X-ray Observatory. We divide the full sample into subsamples of ~20 clusters based on redshift and central density, performing a joint X-ray spectral fit to all clusters in a subsample simultaneously, assuming self-similarity of the temperature profile. This approach allows us to constrain the shape of the temperature profile over 0 < r < 1.5R (500), which would be impossible on a per-cluster basis, since the observations of individual clusters have, on average, 2000 X-ray counts. The results presented here represent the first constraints on the evolution of the average temperature profile from z = 0 to z = 1.2. We find that high-z (0.6 < z < 1.2) clusters are slightly (~30%) cooler both in the inner (r < 0.1R (500)) and outer (r > R (500)) regions than their low-z (0.3 < z < 0.6) counterparts. Combining the average temperature profile with measured gas density profiles from our earlier work, we infer the average pressure and entropy profiles for each subsample. Confirming earlier results from this data set, we find an absence of strong cool cores at high z, manifested in this analysis as a significantly lower observed pressure in the central 0.1R (500) of the high-z cool-core subset of clusters compared to the low-z cool-core subset. Overall, our observed pressure profiles agree well with earlier lower-redshift measurements, suggesting minimal redshift evolution in the pressure profile outside of the core. We find no measurable redshift evolution in the entropy profile at r lsim 0.7R (500)—this may reflect a long-standing balance between cooling and feedback over long timescales and large physical scales. We observe a slight flattening of the entropy profile at r gsim R (500) in our high-z subsample. This flattening is consistent with a temperature bias due to the enhanced (~3×) rate at which group-mass (~2

  1. Selective extraction of high-value phenolic compounds from distillation wastewater of basil (Ocimum basilicum L.) by pressurized liquid extraction.

    Science.gov (United States)

    Pagano, Imma; Sánchez-Camargo, Andrea Del Pilar; Mendiola, Jose Antonio; Campone, Luca; Cifuentes, Alejandro; Rastrelli, Luca; Ibañez, Elena

    2018-01-31

    During the essential oil steam distillation from aromatic herbs, huge amounts of distillation wastewaters (DWWs) are generated. These by-products represent an exceptionally rich source of phenolic compounds such as rosmarinic acid (RA) and caffeic acid (CA). Herein, the alternative use of dried basil DWWs (dDWWs) to perform a selective extraction of RA and CA by pressurized liquid extraction (PLE) employing bio-based solvent was studied. To select the most suitable solvent for PLE, the theoretical modelling of Hansen solubility parameters (HSP) was carried out. This approach allows reducing the list of candidate to two solvents: ethanol and ethyl lactate. Due to the composition of the sample, mixtures of water with those solvents were also tested. An enriched PLE extract in RA (23.90 ± 2.06 mg/g extract) with an extraction efficiency of 75.89 ± 16.03% employing a water-ethanol mixture 25:75 (% v/v) at 50°C was obtained. In the case of CA, a PLE extract with 2.42 ± 0.04 mg/g extract, having an extraction efficiency of 13.86 ± 4.96% using ethanol absolute at 50°C was achieved. DWWs are proposed as new promising sources of natural additives and/or functional ingredients for cosmetic, nutraceutical, and food applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. E3 Ubiquitin Ligase CHIP and NBR1-Mediated Selective Autophagy Protect Additively against Proteotoxicity in Plant Stress Responses

    Science.gov (United States)

    Qi, Jingxia; Chi, Yingjin; Fan, Baofang; Yu, Jing-Quan; Chen, Zhixiang

    2014-01-01

    Plant stress responses require both protective measures that reduce or restore stress-inflicted damage to cellular structures and mechanisms that efficiently remove damaged and toxic macromolecules, such as misfolded and damaged proteins. We have recently reported that NBR1, the first identified plant autophagy adaptor with a ubiquitin-association domain, plays a critical role in plant stress tolerance by targeting stress-induced, ubiquitinated protein aggregates for degradation by autophagy. Here we report a comprehensive genetic analysis of CHIP, a chaperone-associated E3 ubiquitin ligase from Arabidopsis thaliana implicated in mediating degradation of nonnative proteins by 26S proteasomes. We isolated two chip knockout mutants and discovered that they had the same phenotypes as the nbr1 mutants with compromised tolerance to heat, oxidative and salt stresses and increased accumulation of insoluble proteins under heat stress. To determine their functional interactions, we generated chip nbr1 double mutants and found them to be further compromised in stress tolerance and in clearance of stress-induced protein aggregates, indicating additive roles of CHIP and NBR1. Furthermore, stress-induced protein aggregates were still ubiquitinated in the chip mutants. Through proteomic profiling, we systemically identified heat-induced protein aggregates in the chip and nbr1 single and double mutants. These experiments revealed that highly aggregate-prone proteins such as Rubisco activase and catalases preferentially accumulated in the nbr1 mutant while a number of light-harvesting complex proteins accumulated at high levels in the chip mutant after a relatively short period of heat stress. With extended heat stress, aggregates for a large number of intracellular proteins accumulated in both chip and nbr1 mutants and, to a greater extent, in the chip nbr1 double mutant. Based on these results, we propose that CHIP and NBR1 mediate two distinct but complementary anti

  3. E3 ubiquitin ligase CHIP and NBR1-mediated selective autophagy protect additively against proteotoxicity in plant stress responses.

    Science.gov (United States)

    Zhou, Jie; Zhang, Yan; Qi, Jingxia; Chi, Yingjin; Fan, Baofang; Yu, Jing-Quan; Chen, Zhixiang

    2014-01-01

    Plant stress responses require both protective measures that reduce or restore stress-inflicted damage to cellular structures and mechanisms that efficiently remove damaged and toxic macromolecules, such as misfolded and damaged proteins. We have recently reported that NBR1, the first identified plant autophagy adaptor with a ubiquitin-association domain, plays a critical role in plant stress tolerance by targeting stress-induced, ubiquitinated protein aggregates for degradation by autophagy. Here we report a comprehensive genetic analysis of CHIP, a chaperone-associated E3 ubiquitin ligase from Arabidopsis thaliana implicated in mediating degradation of nonnative proteins by 26S proteasomes. We isolated two chip knockout mutants and discovered that they had the same phenotypes as the nbr1 mutants with compromised tolerance to heat, oxidative and salt stresses and increased accumulation of insoluble proteins under heat stress. To determine their functional interactions, we generated chip nbr1 double mutants and found them to be further compromised in stress tolerance and in clearance of stress-induced protein aggregates, indicating additive roles of CHIP and NBR1. Furthermore, stress-induced protein aggregates were still ubiquitinated in the chip mutants. Through proteomic profiling, we systemically identified heat-induced protein aggregates in the chip and nbr1 single and double mutants. These experiments revealed that highly aggregate-prone proteins such as Rubisco activase and catalases preferentially accumulated in the nbr1 mutant while a number of light-harvesting complex proteins accumulated at high levels in the chip mutant after a relatively short period of heat stress. With extended heat stress, aggregates for a large number of intracellular proteins accumulated in both chip and nbr1 mutants and, to a greater extent, in the chip nbr1 double mutant. Based on these results, we propose that CHIP and NBR1 mediate two distinct but complementary anti

  4. Novel rat Alzheimer's disease models based on AAV-mediated gene transfer to selectively increase hippocampal Aβ levels

    Directory of Open Access Journals (Sweden)

    Dicker Bridget L

    2007-06-01

    Full Text Available Abstract Background Alzheimer's disease (AD is characterized by a decline in cognitive function and accumulation of amyloid-β peptide (Aβ in extracellular plaques. Mutations in amyloid precursor protein (APP and presenilins alter APP metabolism resulting in accumulation of Aβ42, a peptide essential for the formation of amyloid deposits and proposed to initiate the cascade leading to AD. However, the role of Aβ40, the more prevalent Aβ peptide secreted by cells and a major component of cerebral Aβ deposits, is less clear. In this study, virally-mediated gene transfer was used to selectively increase hippocampal levels of human Aβ42 and Aβ40 in adult Wistar rats, allowing examination of the contribution of each to the cognitive deficits and pathology seen in AD. Results Adeno-associated viral (AAV vectors encoding BRI-Aβ cDNAs were generated resulting in high-level hippocampal expression and secretion of the specific encoded Aβ peptide. As a comparison the effect of AAV-mediated overexpression of APPsw was also examined. Animals were tested for development of learning and memory deficits (open field, Morris water maze, passive avoidance, novel object recognition three months after infusion of AAV. A range of impairments was found, with the most pronounced deficits observed in animals co-injected with both AAV-BRI-Aβ40 and AAV-BRI-Aβ42. Brain tissue was analyzed by ELISA and immunohistochemistry to quantify levels of detergent soluble and insoluble Aβ peptides. BRI-Aβ42 and the combination of BRI-Aβ40+42 overexpression resulted in elevated levels of detergent-insoluble Aβ. No significant increase in detergent-insoluble Aβ was seen in the rats expressing APPsw or BRI-Aβ40. No pathological features were noted in any rats, except the AAV-BRI-Aβ42 rats which showed focal, amorphous, Thioflavin-negative Aβ42 deposits. Conclusion The results show that AAV-mediated gene transfer is a valuable tool to model aspects of AD pathology in

  5. AFLP genome scan in the black rat (Rattus rattus) from Madagascar: detecting genetic markers undergoing plague-mediated selection.

    Science.gov (United States)

    Tollenaere, C; Duplantier, J-M; Rahalison, L; Ranjalahy, M; Brouat, C

    2011-03-01

    The black rat (Rattus rattus) is the main reservoir of plague (Yersinia pestis infection) in Madagascar's rural zones. Black rats are highly resistant to plague within the plague focus (central highland), whereas they are susceptible where the disease is absent (low altitude zone). To better understand plague wildlife circulation and host evolution in response to a highly virulent pathogen, we attempted to determine genetic markers associated with plague resistance in this species. To this purpose, we combined a population genomics approach and an association study, both performed on 249 AFLP markers, in Malagasy R. rattus. Simulated distributions of genetic differentiation were compared to observed data in four independent pairs, each consisting of one population from the plague focus and one from the plague-free zone. We found 22 loci (9% of 249) with higher differentiation in at least two independent population pairs or with combining P-values over the four pairs significant. Among the 22 outlier loci, 16 presented significant association with plague zone (plague focus vs. plague-free zone). Population genetic structure inferred from outlier loci was structured by plague zone, whereas the neutral loci dataset revealed structure by geography (eastern vs. western populations). A phenotype association study revealed that two of the 22 loci were significantly associated with differentiation between dying and surviving rats following experimental plague challenge. The 22 outlier loci identified in this study may undergo plague selective pressure either directly or more probably indirectly due to hitchhiking with selected loci. © 2010 Blackwell Publishing Ltd.

  6. The role of gene duplication and unconstrained selective pressures in the melanopsin gene family evolution and vertebrate circadian rhythm regulation.

    Directory of Open Access Journals (Sweden)

    Rui Borges

    Full Text Available Melanopsin is a photosensitive cell protein involved in regulating circadian rhythms and other non-visual responses to light. The melanopsin gene family is represented by two paralogs, OPN4x and OPN4m, which originated through gene duplication early in the emergence of vertebrates. Here we studied the melanopsin gene family using an integrated gene/protein evolutionary approach, which revealed that the rhabdomeric urbilaterian ancestor had the same amino acid patterns (DRY motif and the Y and E conterions as extant vertebrate species, suggesting that the mechanism for light detection and regulation is similar to rhabdomeric rhodopsins. Both OPN4m and OPN4x paralogs are found in vertebrate genomic paralogons, suggesting that they diverged following this duplication event about 600 million years ago, when the complex eye emerged in the vertebrate ancestor. Melanopsins generally evolved under negative selection (ω = 0.171 with some minor episodes of positive selection (proportion of sites = 25% and functional divergence (θ(I = 0.349 and θ(II = 0.126. The OPN4m and OPN4x melanopsin paralogs show evidence of spectral divergence at sites likely involved in melanopsin light absorbance (200F, 273S and 276A. Also, following the teleost lineage-specific whole genome duplication (3R that prompted the teleost fish radiation, type I divergence (θ(I = 0.181 and positive selection (affecting 11% of sites contributed to amino acid variability that we related with the photo-activation stability of melanopsin. The melanopsin intracellular regions had unexpectedly high variability in their coupling specificity of G-proteins and we propose that Gq/11 and Gi/o are the two G-proteins most-likely to mediate the melanopsin phototransduction pathway. The selection signatures were mainly observed on retinal-related sites and the third and second intracellular loops, demonstrating the physiological plasticity of the melanopsin protein group. Our results provide new

  7. Evidence of market-driven size-selective fishing and the mediating effects of biological and institutional factors.

    Science.gov (United States)

    Reddy, Sheila M W; Wentz, Allison; Aburto-Oropeza, Octavio; Maxey, Martin; Nagavarapu, Sriniketh; Leslie, Heather M

    2013-06-01

    Market demand is often ignored or assumed to lead uniformly to the decline of resources. Yet little is known about how market demand influences natural resources in particular contexts, or the mediating effects of biological or institutional factors. Here, we investigate this problem by examining the Pacific red snapper (Lutjanus peru) fishery around La Paz, Mexico, where medium or "plate-sized" fish are sold to restaurants at a premium price. If higher demand for plate-sized fish increases the relative abundance of the smallest (recruit size class) and largest (most fecund) fish, this may be a market mechanism to increase stocks and fishermen's revenues. We tested this hypothesis by estimating the effect of prices on the distribution of catch across size classes using daily records of prices and catch. We linked predictions from this economic choice model to a staged-based model of the fishery to estimate the effects on the stock and revenues from harvest. We found that the supply of plate-sized fish increased by 6%, while the supply of large fish decreased by 4% as a result of a 13% price premium for plate-sized fish. This market-driven size selection increased revenues (14%) but decreased total fish biomass (-3%). However, when market-driven size selection was combined with limited institutional constraints, both fish biomass (28%) and fishermen's revenue (22%) increased. These results show that the direction and magnitude of the effects of market demand on biological populations and human behavior can depend on both biological attributes and institutional constraints. Fisheries management may capitalize on these conditional effects by implementing size-based regulations when economic and institutional incentives will enhance compliance, as in the case we describe here, or by creating compliance enhancing conditions for existing regulations.

  8. Dual oxidase 2 generated reactive oxygen species selectively mediate the induction of mucins by epidermal growth factor in enterocytes.

    Science.gov (United States)

    Damiano, Simona; Morano, Annalisa; Ucci, Valentina; Accetta, Roberta; Mondola, Paolo; Paternò, Roberto; Avvedimento, V Enrico; Santillo, Mariarosaria

    2015-03-01

    Dual oxidase 2 enzyme is a member of the reactive oxygen species-generating cell membrane NADPH oxidases involved in mucosal innate immunity. It is not known if the biological activity of dual oxidase 2 is mediated by direct bacterial killing by reactive oxygen species produced by the enzyme or by the same reactive oxygen species acting as second messengers that stimulate novel gene expression. To uncover the role of reactive oxygen species and dual oxidases as signaling molecules, we have dissected the pathway triggered by epidermal growth factor to induce mucins, the principal protective components of gastrointestinal mucus. We show that dual oxidase 2 is essential for selective epidermal growth factor induction of the transmembrane MUC3 and the secreted gel-forming MUC5AC mucins. Reactive oxygen species generated by dual oxidase 2 stabilize tyrosine phosphorylation of epidermal growth factor receptor and induce MUC3 and MUC5AC through persistent activation of extracellular signal-regulated kinases 1/2-protein kinase C. Knocking down dual oxidase 2 by selective RNA targeting (siRNA) reduced epidermal growth factor receptor phosphorylation, and MUC3 and MUC5AC gene expression. Extracellular reactive oxygen species produced by dual oxidase 2, upon stimulation by epidermal growth factor, stabilize epidermal growth factor receptor phosphorylation and activate extracellular signal-regulated kinases 1/2-protein kinase C which induce MUC5AC and MUC3. Extracellular reactive oxygen species produced by dual oxidase 2 that are known to directly kill bacteria, also contribute to the maintenance of the epidermal growth factor-amplification loop, which induces mucins. These data suggest a new function of dual oxidase 2 protein in the luminal protection of the gastrointestinal tract through the induction of mucin expression by growth factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Evidence of market-driven size-selective fishing and the mediating effects of biological and institutional factors

    Science.gov (United States)

    Reddy, Sheila M. W.; Wentz, Allison; Aburto-Oropeza, Octavio; Maxey, Martin; Nagavarapu, Sriniketh; Leslie, Heather M.

    2014-01-01

    Market demand is often ignored or assumed to lead uniformly to the decline of resources. Yet little is known about how market demand influences natural resources in particular contexts, or the mediating effects of biological or institutional factors. Here, we investigate this problem by examining the Pacific red snapper (Lutjanus peru) fishery around La Paz, Mexico, where medium or “plate-sized” fish are sold to restaurants at a premium price. If higher demand for plate-sized fish increases the relative abundance of the smallest (recruit size class) and largest (most fecund) fish, this may be a market mechanism to increase stocks and fishermen’s revenues. We tested this hypothesis by estimating the effect of prices on the distribution of catch across size classes using daily records of prices and catch. We linked predictions from this economic choice model to a staged-based model of the fishery to estimate the effects on the stock and revenues from harvest. We found that the supply of plate-sized fish increased by 6%, while the supply of large fish decreased by 4% as a result of a 13% price premium for plate-sized fish. This market-driven size selection increased revenues (14%) but decreased total fish biomass (−3%). However, when market-driven size selection was combined with limited institutional constraints, both fish biomass (28%) and fishermen’s revenue (22%) increased. These results show that the direction and magnitude of the effects of market demand on biological populations and human behavior can depend on both biological attributes and institutional constraints. Fisheries management may capitalize on these conditional effects by implementing size-based regulations when economic and institutional incentives will enhance compliance, as in the case we describe here, or by creating compliance enhancing conditions for existing regulations. PMID:23865225

  10. Jumping the nuclear envelop barrier: Improving polyplex-mediated gene transfection efficiency by a selective CDK1 inhibitor RO-3306.

    Science.gov (United States)

    Zhou, Xuefei; Liu, Xiangrui; Zhao, Bingxiang; Liu, Xin; Zhu, Dingcheng; Qiu, Nasha; Zhou, Quan; Piao, Ying; Zhou, Zhuxian; Tang, Jianbin; Shen, Youqing

    2016-07-28

    Successful transfection of plasmid DNA (pDNA) requires intranuclear internalization of pDNA effectively and the nuclear envelope appears to be one of the critical intracellular barriers for polymer mediated pDNA delivery. Polyethylenimine (PEI), as the classic cationic polymer, compact the negatively charged pDNA tightly and make up stable polyplexes. The polyplexes are too large to enter the nuclear through nuclear pores and it is believed that the nuclear envelope breakdown in mitosis could facilitate the nuclear entry of polyplexes. To jump the nuclear envelope barrier, we used a selective and reversible CDK1 inhibitor RO-3306 to control the G2/M transition of the cell cycle and increased the proportion of mitotic cells which have disappeared nuclear envelope during transfection. Herein, we show that RO-3306 remarkably increases the transfection efficiency of PEI polyplexes through enhanced nuclear localization of PEI and pDNA. However, RO-3306 is less effective to the charge-reversal polymer poly[(2-acryloyl)ethyl(p-boronic acid benzyl)diethylammonium bromide] (B-PDEAEA) which responses to cellular stimuli and releases free pDNA in cytoplasm. Our findings not only offer new opportunities for improving non-viral based gene delivery but also provide theoretical support for the rational design of novel functional polymers for gene delivery. We also report current data showing that RO-3306 synergizes TRAIL gene induced apoptosis in cancer cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Synaptic excitation mediated by AMPA receptors in rat cerebellar slices is selectively enhanced by aniracetam and cyclothiazide.

    Science.gov (United States)

    Boxall, A R; Garthwaite, J

    1995-05-01

    AMPA receptors mediate fast, glutamatergic synaptic transmission in the central nervous system. The time-course of the associated postsynaptic current has been suggested to be determined principally by the kinetics of glutamate binding and receptor desensitization. Aniracetam and cyclothiazide are drugs capable of selectively preventing desensitization of the AMPA receptor. To investigate the relevance of desensitization to fast synaptic transmission in the cerebellum we have tested these compounds against AMPA-induced depolarizations and postsynaptic potentials using the grease-gap recording technique. Aniracetam (1 microM-5 mM) and cyclothiazide (1 microM-500 microM) both enhanced the depolarising action of AMPA (1 microM) on Purkinje cells in a concentration-dependent manner. At the highest concentrations tested, the increases over controls were approximately 600% and 800% respectively. Aniracetam also increased, in a concentration-dependent manner, the amplitude of the evoked synaptic potentials of both parallel fibre-Purkinje cell and mossy fibre-granule cell pathways, with the highest concentrations tested enhancing the potentials by approximately 60% and 75% respectively. These data suggest that, at two different synapses in the cerebellum, AMPA receptor desensitization occurs physiologically and is likely to contribute to the shape of fast synaptic currents.

  12. Delineating Selection and Mediation Effects among Childhood Personality and Environmental Risk Factors in the Development of Adolescent Substance Abuse

    Science.gov (United States)

    Hicks, Brian M.; Johnson, Wendy; Durbin, C. Emily; Blonigen, Daniel M.; Iacono, William G.; McGue, Matt

    2014-01-01

    Utilizing the large, longitudinal Minnesota Twin Family Study (N = 2510; 96% European American ancestry), we examined the influence of several person-environment transactions on adolescent substance abuse. We focused on the two childhood personality traits found to be most predictive of substance abuse in this sample—socialization (willingness to follow rules and endorse conventional values) and boldness (social engagement and assurance, stress resilience, thrill seeking)—and the environmental variables of antisocial and prosocial peers, academic engagement, parent-child relationship quality, and stressful life events. Path analysis revealed that low socialization had a selection effect for each environmental risk factor, that is, socialization at age 11 predicted environmental risk at age 14, after controlling for the stability of the environmental variables from ages 11 to 14. Antisocial peers and academic engagement at age 14 then mediated some of the risk of low socialization on substance abuse at age 17, but the majority of risk for substance abuse was accounted for by the stability of socialization from age 11 to 14. Boldness at age 11 also increased risk for substance abuse, but did so primarily via a direct effect. The findings help to parse the nature of person-environment transactions across multiple personality traits and contextual risk factors that contribute to adolescent substance abuse. PMID:24337735

  13. Achieving the Optimal Peri-implant Soft Tissue Profile by the Selective Pressure Method via Provisional Restorations in the Esthetic Zone.

    Science.gov (United States)

    Nam, Jung; Aranyarachkul, Prasit

    2015-01-01

    For the successful single-tooth implant therapy in the esthetics zone, achieving an ideal peri-implant soft tissue profile is paramount. It can achieve by the manipulation of the provisional restorations. This clinical report demonstrate the selective pressure method and concave transmucosal profile of the provisional restorations to achieve the ideal and stable gingival profile in esthetic single tooth implant restorations. The selective pressure method and the concave transmucosal profile in implant provisional restorations facilitate stable and harmonized peri-implant gingival tissue in the esthetic zone. © 2015 Wiley Periodicals, Inc.

  14. Ab initio molecular orbital study on the G-selectivity of GGG triplet in copper(I)-mediated one-electron oxidation.

    Science.gov (United States)

    Yoshioka, Yasunori; Kawai, Hiroko; Sato, Tomoko; Yamaguchi, Kizashi; Saito, Isao

    2003-02-19

    The G-selectivity for Cu(I)-mediated one-electron oxidation of 5'-TG(1)G(2)G(3)-3' and 5'-CG(1)G(2)G(3)-3' has been examined by ab initio molecular orbital calculations. It was confirmed that G(1) is selectively damaged by Cu(I) ion for both 5'-TG(1)G(2)G(3)-3' and 5'-CG(1)G(2)G(3)-3', being good agreement with experimental results. The Cu(I)-mediated G(1)-selectivity is primarily due to the stability of the Cu(I)-coordinated complex, [-XG(1)G(2)G(3)-,-Cu(I)(H(2)O)(3)](+). The Cu(I) ion coordinates selectively to N7 of G(2) of 5'-G(1)G(2)G(3)-3' rather than N7 of G(1). The G(2)-selective coordination induces the G(1)-selective trap of a hole that is created by one-electron oxidation and migrates to GGG triplet. Therefore, the radical cation of G(1) is selectively created in both 5'-TG(1)G(2)G(3)-3' and 5'-CG(1)G(2)G(3)-3', giving the G(1)-selective damage of 5'-G(1)G(2)G(3)-3'.

  15. Lipocalin 2 Imparts Selective Pressure on Bacterial Growth in the Bladder and Is Elevated in Women with Urinary Tract Infection

    Science.gov (United States)

    Steigedal, Magnus; Marstad, Anne; Haug, Markus; Damås, Jan K.; Strong, Roland K.; Roberts, Pacita L.; Himpsl, Stephanie D.; Stapleton, Ann; Hooton, Thomas M.; Mobley, Harry L. T.; Hawn, Thomas R.

    2014-01-01

    Competition for iron is a critical component of successful bacterial infections, but the underlying in vivo mechanisms are poorly understood. We have previously demonstrated that lipocalin 2 (LCN2) is an innate immunity protein that binds to bacterial siderophores and starves them for iron, thus representing a novel host defense mechanism to infection. In the present study we show that LCN2 is secreted by the urinary tract mucosa and protects against urinary tract infection (UTI). We found that LCN2 was expressed in the bladder, ureters, and kidneys of mice subject to UTI. LCN2 was protective with higher bacterial numbers retrieved from bladders of Lcn2-deficient mice than from wild-type mice infected with the LCN2-sensitive Escherichia coli strain H9049. Uropathogenic E. coli mutants in siderophore receptors for salmochelin, aerobactin, or yersiniabactin displayed reduced fitness in wild-type mice, but not in mice deficient of LCN2, demonstrating that LCN2 imparts a selective pressure on bacterial growth in the bladder. In a human cohort of women with recurrent E. coli UTIs, urine LCN2 levels were associated with UTI episodes and with levels of bacteriuria. The number of siderophore systems was associated with increasing bacteriuria during cystitis. Our data demonstrate that LCN2 is secreted by the urinary tract mucosa in response to uropathogenic E. coli challenge and acts in innate immune defenses as a colonization barrier that pathogens must overcome to establish infection. PMID:25398327

  16. Selective pressurized liquid extraction technique capable of analyzing dioxins, furans, and PCBs in clams and crab tissue.

    Science.gov (United States)

    Subedi, Bikram; Aguilar, Lissette; Williams, E Spencer; Brooks, Bryan W; Usenko, Sascha

    2014-04-01

    A selective pressurized liquid extraction technique (SPLE) was developed for the analysis of polychlorodibenzo-p-dioxins, polychlorodibenzofurans (PCDD/Fs) and dioxin-like polychlorobiphenyls (dl-PCBs) in clam and crab tissue. The SPLE incorporated multiple cleanup adsorbents (alumina, florisil, silica gel, celite, and carbopack) within the extraction cell. Tissue extracts were analyzed by high resolution gas chromatography coupled with electron capture negative ionization mass spectrometry. Mean recovery (n = 3) and percent relative standard deviation for PCDD/Fs and dl-PCBs in clam and crabs was 89 ± 2.3 and 85 ± 4.0, respectively. The SPLE method was applied to clams and crabs collected from the San Jacinto River Waste Pits, a Superfund site in Houston, TX. The dl-PCBs concentrations in clams and crabs ranged from 50 to 2,450 and 5 to 800 ng/g ww, respectively. Sample preparation time and solvents were reduced by 92 % and 65 %, respectively, as compared to USEPA method 1613.

  17. E3 ubiquitin ligase CHIP and NBR1-mediated selective autophagy protect additively against proteotoxicity in plant stress responses.

    Directory of Open Access Journals (Sweden)

    Jie Zhou

    2014-01-01

    Full Text Available Plant stress responses require both protective measures that reduce or restore stress-inflicted damage to cellular structures and mechanisms that efficiently remove damaged and toxic macromolecules, such as misfolded and damaged proteins. We have recently reported that NBR1, the first identified plant autophagy adaptor with a ubiquitin-association domain, plays a critical role in plant stress tolerance by targeting stress-induced, ubiquitinated protein aggregates for degradation by autophagy. Here we report a comprehensive genetic analysis of CHIP, a chaperone-associated E3 ubiquitin ligase from Arabidopsis thaliana implicated in mediating degradation of nonnative proteins by 26S proteasomes. We isolated two chip knockout mutants and discovered that they had the same phenotypes as the nbr1 mutants with compromised tolerance to heat, oxidative and salt stresses and increased accumulation of insoluble proteins under heat stress. To determine their functional interactions, we generated chip nbr1 double mutants and found them to be further compromised in stress tolerance and in clearance of stress-induced protein aggregates, indicating additive roles of CHIP and NBR1. Furthermore, stress-induced protein aggregates were still ubiquitinated in the chip mutants. Through proteomic profiling, we systemically identified heat-induced protein aggregates in the chip and nbr1 single and double mutants. These experiments revealed that highly aggregate-prone proteins such as Rubisco activase and catalases preferentially accumulated in the nbr1 mutant while a number of light-harvesting complex proteins accumulated at high levels in the chip mutant after a relatively short period of heat stress. With extended heat stress, aggregates for a large number of intracellular proteins accumulated in both chip and nbr1 mutants and, to a greater extent, in the chip nbr1 double mutant. Based on these results, we propose that CHIP and NBR1 mediate two distinct but

  18. Fire-mediated disruptive selection can explain the reseeder-resprouter dichotomy in Mediterranean-type vegetation.

    Science.gov (United States)

    Altwegg, Res; De Klerk, Helen M; Midgley, Guy F

    2015-02-01

    Crown fire is a key selective pressure in Mediterranean-type plant communities. Adaptive responses to fire regimes involve trade-offs between investment for persistence (fire survival and resprouting) and reproduction (fire mortality, fast growth to reproductive maturity, and reseeding) as investments that enhance adult survival lower growth and reproductive rates. Southern hemisphere Mediterranean-type ecosystems are dominated by species with either endogenous regeneration from adult resprouting or fire-triggered seedling recruitment. Specifically, on nutrient-poor soils, these are either resprouting or reseeding life histories, with few intermediate forms, despite the fact that the transition between strategies is evolutionarily labile. How did this strong dichotomy evolve? We address this question by developing a stochastic demographic model to assess determinants of relative fitness of reseeders, resprouters and hypothetical intermediate forms. The model was parameterised using published demographic data from South African protea species and run over various relevant fire regime parameters facets. At intermediate fire return intervals, trade-offs between investment in growth versus fire resilience can cause fitness to peak at either of the extremes of the reseeder-resprouter continuum, especially when assuming realistic non-linear shapes for these trade-offs. Under these circumstances, the fitness landscape exhibits a saddle which could lead to disruptive selection. The fitness gradient between the peaks was shallow, which may explain why this life-history trait is phylogenetically labile. Resprouters had maximum fitness at shorter fire-return intervals than reseeders. The model suggests that a strong dichotomy in fire survival strategy depends on a non-linear trade-off between growth and fire persistence traits.

  19. Cold stress accentuates pressure overload-induced cardiac hypertrophy and contractile dysfunction: role of TRPV1/AMPK-mediated autophagy.

    Science.gov (United States)

    Lu, Songhe; Xu, Dezhong

    2013-12-06

    Severe cold exposure and pressure overload are both known to prompt oxidative stress and pathological alterations in the heart although the interplay between the two remains elusive. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel activated in response to a variety of exogenous and endogenous physical and chemical stimuli including heat and capsaicin. The aim of this study was to examine the impact of cold exposure on pressure overload-induced cardiac pathological changes and the mechanism involved. Adult male C57 mice were subjected to abdominal aortic constriction (AAC) prior to exposure to cold temperature (4 °C) for 4 weeks. Cardiac geometry and function, levels of TRPV1, mitochondrial, and autophagy-associated proteins including AMPK, mTOR, LC3B, and P62 were evaluated. Sustained cold stress triggered cardiac hypertrophy, compromised depressed myocardial contractile capacity including lessened fractional shortening, peak shortening, and maximal velocity of shortening/relengthening, enhanced ROS production, and mitochondrial injury, the effects of which were negated by the TRPV1 antagonist SB366791. Western blot analysis revealed upregulated TRPV1 level and AMPK phosphorylation, enhanced ratio of LC3II/LC3I, and downregulated P62 following cold exposure. Cold exposure significantly augmented AAC-induced changes in TRPV1, phosphorylation of AMPK, LC3 isoform switch, and p62, the effects of which were negated by SB366791. In summary, these data suggest that cold exposure accentuates pressure overload-induced cardiac hypertrophy and contractile defect possibly through a TRPV1 and autophagy-dependent mechanism. Copyright © 2013. Published by Elsevier Inc.

  20. Bone metastasis in prostate cancer: Recurring mitochondrial DNA mutation reveals selective pressure exerted by the bone microenvironment.

    Science.gov (United States)

    Arnold, Rebecca S; Fedewa, Stacey A; Goodman, Michael; Osunkoya, Adeboye O; Kissick, Haydn T; Morrissey, Colm; True, Lawrence D; Petros, John A

    2015-09-01

    include a tRNA Arg mutation at n.p. 10436 and a tRNA Thr mutation at n.p. 15928. The tRNA Arg mutation was restricted to bone metastases and occurred in three of 10 patients (30%). Somatic mutation at 15928 was not restricted to the bone and also occurred in three patients. Mitochondrial genomic variation was greater in metastatic sites than in the primary tumor and bone metastases had statistically significantly greater numbers of somatic mutations than either the primary or the soft tissue metastases. The genome was not mutated randomly. At least one mutational "hot-spot" was identified at the individual base level (nucleotide position 10398 in bone metastases) indicating a pervasive selective pressure for bone metastatic cells that had acquired the 10398 mtDNA mutation. Two additional recurrent mutations (tRNA Arg and tRNA Thr) support the concept of bone site-specific "survival of the fittest" as revealed by variation in the mitochondrial genome and selective pressure exerted by the metastatic site. Published by Elsevier Inc.

  1. HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of apobec

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette [Los Alamos National Laboratory; Bhattacharya, Tanmoy [Los Alamos National Laboratory; Giorgi, Elena [Los Alamos National Laboratory; Gaschen, B [Los Alamos National Laboratory; Daniels, M [Los Alamos National Laboratory

    2009-01-01

    The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, represent adaptation for rapid growth in a newly infected host, or reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV -I env coding sequences in 81 very early B SUbtype infections previously shown to have resulted from transmission or expansion of single viruses (n=78) or two closely related viruses (n=3). In these cases the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 envand identified a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either (i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual's HLA or (ii) in a nucleotide context indicative of APOBEC mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was both embedded in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp4l. We also examined the distribution, extent, and sequence context of insertions and deletions and provide evidence that the length

  2. Toll‐Like Receptor‐2 Mediates Adaptive Cardiac Hypertrophy in Response to Pressure Overload Through Interleukin‐1β Upregulation via Nuclear Factor κB Activation

    Science.gov (United States)

    Higashikuni, Yasutomi; Tanaka, Kimie; Kato, Megumi; Nureki, Osamu; Hirata, Yasunobu; Nagai, Ryozo; Komuro, Issei; Sata, Masataka

    2013-01-01

    Background Inflammation is induced in the heart during the development of cardiac hypertrophy. The initiating mechanisms and the role of inflammation in cardiac hypertrophy, however, remain unclear. Toll‐like receptor‐2 (TLR2) recognizes endogenous molecules that induce noninfectious inflammation. Here, we examined the role of TLR2‐mediated inflammation in cardiac hypertrophy. Methods and Results At 2 weeks after transverse aortic constriction, Tlr2−/− mice showed reduced cardiac hypertrophy and fibrosis with greater left ventricular dilatation and impaired systolic function compared with wild‐type mice, which indicated impaired cardiac adaptation in Tlr2−/− mice. Bone marrow transplantation experiment revealed that TLR2 expressed in the heart, but not in bone marrow–derived cells, is important for cardiac adaptive response to pressure overload. In vitro experiments demonstrated that TLR2 signaling can induce cardiomyocyte hypertrophy and fibroblast and vascular endothelial cell proliferation through nuclear factor–κB activation and interleukin‐1β upregulation. Systemic administration of a nuclear factor–κB inhibitor or anti–interleukin‐1β antibodies to wild‐type mice resulted in impaired adaptive cardiac hypertrophy after transverse aortic constriction. We also found that heat shock protein 70, which was increased in murine plasma after transverse aortic constriction, can activate TLR2 signaling in vitro and in vivo. Systemic administration of anti–heat shock protein 70 antibodies to wild‐type mice impaired adaptive cardiac hypertrophy after transverse aortic constriction. Conclusions Our results demonstrate that TLR2‐mediated inflammation induced by extracellularly released heat shock protein 70 is essential for adaptive cardiac hypertrophy in response to pressure overload. Thus, modulation of TLR2 signaling in the heart may provide a novel strategy for treating heart failure due to inadequate adaptation to hemodynamic

  3. Pattern of intraocular pressure reduction following laser trabeculoplasty in open-angle glaucoma patients: comparison between selective and nonselective treatment

    Directory of Open Access Journals (Sweden)

    Almeida Jr ED

    2011-07-01

    Full Text Available Eglailson Dantas Almeida Júnior1, Luciano Moreira Pinto1,2, Rodrigo Antonio Brant Fernandes1,2, Tiago Santos Prata1,31Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil; 2Cerpo Oftalmologia, São Paulo, Brazil; 3Hospital Medicina dos Olhos, São Paulo, BrazilObjective: To compare the pattern of intraocular pressure (IOP reduction following selective laser trabeculoplasty (SLT versus argon laser trabeculoplasty (ALT in open-angle glaucoma (OAG patients, and to investigate the ability of initial IOP reduction to predict mid-term success.Methods: A prospective, nonrandomized, interventional case series was carried out. Consecutive uncontrolled OAG glaucoma patients underwent SLT or ALT; the same preoperative medical regimen was maintained during follow-up. Data collected included age, type of OAG, pre- and postoperative IOP, number of glaucoma medications, and surgical complications. Post-treatment assessments were scheduled at day 1 and 7 and months 1, 3, and 6.Results: A total of 45 patients (45 eyes were enrolled [SLT group (n = 25; ALT group (n = 20]. Groups were similar for age, baseline IOP, and number of glaucoma medications (P ≥ 0.12. We found no significant differences in mean IOP reduction between SLT (5.1 ± 2.5 mmHg; 26.6% and ALT (4.4 ± 2.8 mmHg; 22.8% groups at month 6 (P = 0.38. Success rates (IOP ≤ 16 mmHg and IOP reduction ≥25% at last follow-up visit were similar for SLT (72% and ALT (65% groups (P = 0.36. Comparing the pattern of IOP reduction (% of IOP reduction at each visit between groups, we found a greater effect following SLT compared with ALT at day 7 (23.7% ± 13.7% vs 8.1% ± 9.5%; P < 0.001. No significant differences were observed at other time points (P ≥ 0.32. Additionally, the percentage of IOP reduction at day 7 and at month 6 were significantly correlated in the SLT group (R2 = 0.36; P < 0.01, but not in the ALT group (P = 0.89. Early postoperative success predicted late

  4. Association between maternal education and blood pressure: mediation evidence through height components in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

    Science.gov (United States)

    Rodríguez López, Santiago; Bensenor, Isabela M; Giatti, Luana; Molina, Maria Del Carmen; Lotufo, Paulo A

    2017-05-01

    Maternal education influences skeletal growth and offspring adult blood pressure (BP). Height components are negatively associated with BP in high-income countries. To evaluate the association between maternal education and offspring adult systolic and diastolic BP (SBP/DBP), assessing whether different height components might mediate such an association. Simple mediation modelling was used to evaluate the maternal education-offspring SBP/DBP association, estimating the contribution of offspring height components, in a cross-sectional sample of 13 571 Brazilians aged 34-75 from the ELSA-Brasil study. After full adjustment for confounders, and compared to participants whose mothers received low education, those whose mothers received high education had, on average, 0.2 mm Hg lower SBP (95% CI = -0.274, -0.132), as result of the link between maternal education and offspring adult height which, in turn, influenced SBP. Thus, 18-26% of the maternal education-SBP association occurred indirectly, through height, trunk and leg length, alternatively. Better maternal education might influence higher leg and trunk lengths in offspring, which, in turn, might contribute to prevent higher BP in adults. The negative height-BP association reported in high-income countries is also present in a middle-income country with more recent economic development.

  5. Alcohol consumption and electrocardiographic left ventricular hypertrophy and mediation by elevated blood pressure in older Chinese men: the Guangzhou Biobank Cohort Study.

    Science.gov (United States)

    Long, Mei Jing; Jiang, Chao Qiang; Lam, Tai Hing; Lin, Jie Ming; Chan, Yap Hang; Zhang, Wei Sen; Jin, Ya Li; Liu, Bin; Thomas, G Neil; Cheng, Kar Keung

    2013-09-01

    Chinese people have a markedly lower alcohol consumption than people in the West. Whether alcohol consumption at such levels is associated with left ventricular hypertrophy, and the role of blood pressure (BP) in this relationship is unclear. We investigated the association between alcohol consumption and electrocardiographic left ventricular hypertrophy (ECG-LVH) and the mediating role of BP in Chinese men aged ≥50 years. A case-control analysis was conducted on baseline cross-sectional data from the community-based Guangzhou Biobank Cohort Study (2003-2008), using standard 12-lead resting electrocardiograms. By comparing 191 new ECG-LVH cases with 4311 controls, excessive drinking (>210 g/week) showed excess risks for ECG-LVH (odds ratio [OR] = 1.90, 95% confidence interval [CI] = 1.12-3.24), after adjusting for education, income, occupation, physical activity, smoking, body mass index, fasting glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, BP, and antihypertensive medication. Mediation analysis showed a significant mediating effect of BP on the association between excessive drinking and ECG-LVH: systolic (31%) and diastolic (16%). After multivariate adjustment, no significant association was found between occasional drinking (Alcohol consumption at >210 g/week in Chinese men is an independent risk factor for ECG-LVH. Low power prevented us from examining whether drinking at alcohol and ECG-LVH. A Mendelian randomization approach with a large sample size is warranted to determine the relations among alcohol consumption, BP, and LVH. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Seed trait-mediated selection by rodents affects mutualistic interactions and seedling recruitment of co-occurring tree species.

    Science.gov (United States)

    Zhang, Hongmao; Yan, Chuan; Chang, Gang; Zhang, Zhibin

    2016-02-01

    As mutualists, seed dispersers may significantly affect mutualistic interactions and seedling recruitment of sympatric plants that share similar seed dispersers, but studies are rare. Here, we compared seed dispersal fitness in two co-occurring plant species (Armeniaca sibirica and Amygdalus davidiana) that inhabit warm temperate deciduous forest in northern China. We tested the hypothesis that seed trait-mediated selection by rodents may influence mutualistic interactions with rodents and then seedling establishment of co-occurring plant species. A. davidiana seeds are larger and harder (thick endocarps) than A. sibirica seeds, but they have similar levels of nutrients (crude fat, crude protein), caloric value and tannin. More A. sibirica seedlings are found in the field. Semi-natural enclosure tests indicated that the two seed species were both harvested by the same six rodent species, but that A. sibirica had mutualistic interactions (scatter hoarding) with four rodent species (Apodemus peninsulae, A. agrarius, Sciurotamias davidianus, Tamias sibiricus), and A. davidiana with only one (S. davidianus). Tagged seed dispersal experiments in the field indicated that more A. sibirica seeds were scatter-hoarded by rodents, and more A. sibirica seeds survived to the next spring and became seedlings. A. sibirica seeds derive more benefit from seed dispersal by rodents than A. davidiana seeds, particularly in years with limited seed dispersers, which well explained the higher seedling recruitment of A. sibirica compared with that of A. davidiana under natural conditions. Our results suggest that seed dispersers may play a significant role in seedling recruitment and indirect competition between co-occurring plant species.

  7. The evolution of bat vestibular systems in the face of potential antagonistic selection pressures for flight and echolocation.

    Directory of Open Access Journals (Sweden)

    Kalina T J Davies

    Full Text Available The vestibular system maintains the body's sense of balance and, therefore, was probably subject to strong selection during evolutionary transitions in locomotion. Among mammals, bats possess unique traits that place unusual demands on their vestibular systems. First, bats are capable of powered flight, which in birds is associated with enlarged semicircular canals. Second, many bats have enlarged cochleae associated with echolocation, and both cochleae and semicircular canals share a space within the petrosal bone. To determine how bat vestibular systems have evolved in the face of these pressures, we used micro-CT scans to compare canal morphology across species with contrasting flight and echolocation capabilities. We found no increase in canal radius in bats associated with the acquisition of powered flight, but canal radius did correlate with body mass in bat species from the suborder Yangochiroptera, and also in non-echolocating Old World fruit bats from the suborder Yinpterochiroptera. No such trend was seen in members of the Yinpterochiroptera that use laryngeal echolocation, although canal radius was associated with wing-tip roundedness in this group. We also found that the vestibular system scaled with cochlea size, although the relationship differed in species that use constant frequency echolocation. Across all bats, the shape of the anterior and lateral canals was associated with large cochlea size and small body size respectively, suggesting differential spatial constraints on each canal depending on its orientation within the skull. Thus in many echolocating bats, it seems that the combination of small body size and enlarged cochlea together act as a principal force on the vestibular system. The two main groups of echolocating bats displayed different canal morphologies, in terms of size and shape in relation to body mass and cochlear size, thus suggesting independent evolutionary pathways and offering tentative support for

  8. Monitoring of prestressed concrete pressure vessels. II. performance of selected concrete embedment strain meters under normal and extreme environmental conditions

    International Nuclear Information System (INIS)

    Naus, D.J.; Hurtt, C.C.

    1978-10-01

    Unique types of instrumentation are used in prestressed concrete pressure vessels (PCPVs) to measure strains, stresses, deflections, prestressing forces, moisture content, temperatures, and possibly cracking. Their primary purpose is to monitor these complex structures throughout their 20- to 30-year operating lifetime in order to provide continuing assurance of their reliability and safety. Numerous concrete embedment instrumentation systems are available commercially. Since this instrumentation is important in providing continuing assurance of satisfactory performance of PCPVs, the information provided must be reliable. Therefore, laboratory studies were conducted to evaluate the reliability of these commercially available instrumentation systems. This report, the second in a series related to instrumentation embedded in concrete, presents performance-reliability data for 13 types of selected concrete embedment strain meters which were subjected to a variety of loading environments, including unloaded, thermally loaded, simulated PCPV, and extreme environments. Although only a limited number of meters of each type were tested in any one test series, the composite results of the investigation indicate that the majority of these meters would not be able to provide reliable data throughout the 20- to 30-year anticipated operating life of a PCPV. Specific conclusions drawn from the study are: (1) Improved corrosion-resistant materials and sealing techniques should be developed for meters that are to be used in PCPV environments. (2) There is a need for the development of meters that are capable of surviving in concretes where temperatures in excess of 66 0 C are present for extended periods of time. (3) Research should be conducted on other measurement techniques, such as inductance, capacitance, and fluidics

  9. The evolution of bat vestibular systems in the face of potential antagonistic selection pressures for flight and echolocation.

    Science.gov (United States)

    Davies, Kalina T J; Bates, Paul J J; Maryanto, Ibnu; Cotton, James A; Rossiter, Stephen J

    2013-01-01

    The vestibular system maintains the body's sense of balance and, therefore, was probably subject to strong selection during evolutionary transitions in locomotion. Among mammals, bats possess unique traits that place unusual demands on their vestibular systems. First, bats are capable of powered flight, which in birds is associated with enlarged semicircular canals. Second, many bats have enlarged cochleae associated with echolocation, and both cochleae and semicircular canals share a space within the petrosal bone. To determine how bat vestibular systems have evolved in the face of these pressures, we used micro-CT scans to compare canal morphology across species with contrasting flight and echolocation capabilities. We found no increase in canal radius in bats associated with the acquisition of powered flight, but canal radius did correlate with body mass in bat species from the suborder Yangochiroptera, and also in non-echolocating Old World fruit bats from the suborder Yinpterochiroptera. No such trend was seen in members of the Yinpterochiroptera that use laryngeal echolocation, although canal radius was associated with wing-tip roundedness in this group. We also found that the vestibular system scaled with cochlea size, although the relationship differed in species that use constant frequency echolocation. Across all bats, the shape of the anterior and lateral canals was associated with large cochlea size and small body size respectively, suggesting differential spatial constraints on each canal depending on its orientation within the skull. Thus in many echolocating bats, it seems that the combination of small body size and enlarged cochlea together act as a principal force on the vestibular system. The two main groups of echolocating bats displayed different canal morphologies, in terms of size and shape in relation to body mass and cochlear size, thus suggesting independent evolutionary pathways and offering tentative support for multiple acquisitions of

  10. Characterization of microbial community and antibiotic resistance genes in activated sludge under tetracycline and sulfamethoxazole selection pressure

    International Nuclear Information System (INIS)

    Zhang, Yingying; Geng, Jinju; Ma, Haijun; Ren, Hongqiang; Xu, Ke; Ding, Lili

    2016-01-01

    To investigate the microbial community characteristics, antibiotic resistance genes (ARGs), and bioreactor effluent quality change under tetracycline (TC) and sulfamethoxazole (SMX) selection pressure, sequencing batch reactors (SBRs) were used with environmentally relevant concentration and high-level of TC and SMX concentrations (0, 5 ppb, 50 ppb and 10 ppm). Chemical oxygen demand (COD) and ammonia nitrogen (NH 4 + −N) removals appeared unchanged (p > 0.05) with 5 and 50 ppb, but decreased significantly with 10 ppm (p < 0.05). Extracellular polymeric substances (EPS) concentrations increased significantly with increasing TC or SMX concentrations (p < 0.05). High-throughput 16S rRNA gene sequencing results suggested that Proteobacteria, Actinobacteria and Bacteroidetes were the three most abundant phyla in sludge samples. The Actinobacteria percentages increased with increasing TC or SMX concentration, while Proteobacteria and Bacteroidetes decreased. The microbial diversity achieved its maximum at 5 ppb and decreased with higher concentrations. The total ARGs abundances in sludge increased with addition of TC or SMX, and the higher relative abundances were in the order of sul1 > tetG > sul2 > tetA > intI1 > tetS > tetC. Pearson correlation analysis showed most ARGs (tetA, tetC, tetG, tetK, tetM, sul1) were significantly correlated with intI1 (p < 0.01). - Highlights: • COD and NH 4 + −N removals significantly decrease under 10 ppm TC or SMX. • Activated sludge EPS concentrations increase with increasing TC or SMX concentrations. • TC and SMX affect the microbial community diversity of activated sludge. • Actinobacteria abundances increase with increase of TC or SMX concentration. • ARGs abundance increases with addition of TC or SMX.

  11. The Evolution of Bat Vestibular Systems in the Face of Potential Antagonistic Selection Pressures for Flight and Echolocation

    Science.gov (United States)

    Davies, Kalina T. J.; Bates, Paul J. J.; Maryanto, Ibnu; Cotton, James A.; Rossiter, Stephen J.

    2013-01-01

    The vestibular system maintains the body’s sense of balance and, therefore, was probably subject to strong selection during evolutionary transitions in locomotion. Among mammals, bats possess unique traits that place unusual demands on their vestibular systems. First, bats are capable of powered flight, which in birds is associated with enlarged semicircular canals. Second, many bats have enlarged cochleae associated with echolocation, and both cochleae and semicircular canals share a space within the petrosal bone. To determine how bat vestibular systems have evolved in the face of these pressures, we used micro-CT scans to compare canal morphology across species with contrasting flight and echolocation capabilities. We found no increase in canal radius in bats associated with the acquisition of powered flight, but canal radius did correlate with body mass in bat species from the suborder Yangochiroptera, and also in non-echolocating Old World fruit bats from the suborder Yinpterochiroptera. No such trend was seen in members of the Yinpterochiroptera that use laryngeal echolocation, although canal radius was associated with wing-tip roundedness in this group. We also found that the vestibular system scaled with cochlea size, although the relationship differed in species that use constant frequency echolocation. Across all bats, the shape of the anterior and lateral canals was associated with large cochlea size and small body size respectively, suggesting differential spatial constraints on each canal depending on its orientation within the skull. Thus in many echolocating bats, it seems that the combination of small body size and enlarged cochlea together act as a principal force on the vestibular system. The two main groups of echolocating bats displayed different canal morphologies, in terms of size and shape in relation to body mass and cochlear size, thus suggesting independent evolutionary pathways and offering tentative support for multiple acquisitions of

  12. Characterization of microbial community and antibiotic resistance genes in activated sludge under tetracycline and sulfamethoxazole selection pressure

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yingying; Geng, Jinju, E-mail: jjgeng@nju.edu.cn; Ma, Haijun; Ren, Hongqiang; Xu, Ke; Ding, Lili

    2016-11-15

    To investigate the microbial community characteristics, antibiotic resistance genes (ARGs), and bioreactor effluent quality change under tetracycline (TC) and sulfamethoxazole (SMX) selection pressure, sequencing batch reactors (SBRs) were used with environmentally relevant concentration and high-level of TC and SMX concentrations (0, 5 ppb, 50 ppb and 10 ppm). Chemical oxygen demand (COD) and ammonia nitrogen (NH{sub 4}{sup +}−N) removals appeared unchanged (p > 0.05) with 5 and 50 ppb, but decreased significantly with 10 ppm (p < 0.05). Extracellular polymeric substances (EPS) concentrations increased significantly with increasing TC or SMX concentrations (p < 0.05). High-throughput 16S rRNA gene sequencing results suggested that Proteobacteria, Actinobacteria and Bacteroidetes were the three most abundant phyla in sludge samples. The Actinobacteria percentages increased with increasing TC or SMX concentration, while Proteobacteria and Bacteroidetes decreased. The microbial diversity achieved its maximum at 5 ppb and decreased with higher concentrations. The total ARGs abundances in sludge increased with addition of TC or SMX, and the higher relative abundances were in the order of sul1 > tetG > sul2 > tetA > intI1 > tetS > tetC. Pearson correlation analysis showed most ARGs (tetA, tetC, tetG, tetK, tetM, sul1) were significantly correlated with intI1 (p < 0.01). - Highlights: • COD and NH{sub 4}{sup +}−N removals significantly decrease under 10 ppm TC or SMX. • Activated sludge EPS concentrations increase with increasing TC or SMX concentrations. • TC and SMX affect the microbial community diversity of activated sludge. • Actinobacteria abundances increase with increase of TC or SMX concentration. • ARGs abundance increases with addition of TC or SMX.

  13. Heart rate-mediated blood pressure control in preterm fetal sheep under normal and hypoxic-ischemic conditions.

    Science.gov (United States)

    Zwanenburg, Alex; Jellema, Reint K; Jennekens, Ward; Ophelders, Daan; Vullings, Rik; van Hunnik, Arne; van Pul, Carola; Bennet, Laura; Delhaas, Tammo; Kramer, Boris W; Andriessen, Peter

    2013-04-01

    The understanding of hypoxemia-induced changes in baroreflex function is limited and may be studied in a fetal sheep experiment before, during, and after standardized hypoxic conditions. Preterm fetal lambs were instrumented at 102 d gestation (term: 146 d). At 106 d, intrauterine hypoxia--ischemia was induced by 25 min of umbilical cord occlusion (UCO). Baroreflex-related fluctuations were calculated at 30-min intervals during the first week after UCO by transfer function (cross-spectral) analysis between systolic blood pressure (SBP) and R-R interval fluctuations, estimated in the low-frequency (LF, 0.04-0.15 Hz) band. LF transfer gain (baroreflex sensitivity) and delay (s) reflect the baroreflex function. Baseline did not differ in LF transfer gain and delay between controls and the UCO group. In controls, LF gain showed postnatal increase. By contrast, LF gain gradually decreased in the UCO group, resulting in significantly lower values 4-7 d after UCO. In the UCO group, LF delay increased and differed significantly from controls. Our results show that intrauterine hypoxia-ischemia results in reduced baroreflex sensitivity over a period of 7 d, indicating limited efficacy to buffer BP changes by adapting heart rate. Cardiovascular dysregulation may augment already present cerebral damage after systemic hypoxia-ischemia in the reperfusion period.

  14. Study of Pyridine-Mediated Electrochemical Reduction of CO2 to Methanol at High CO2 Pressure.

    Science.gov (United States)

    Rybchenko, Sergey I; Touhami, Dalila; Wadhawan, Jay D; Haywood, Stephanie K

    2016-07-07

    The recently proposed highly efficient route of pyridine-catalyzed CO2 reduction to methanol was explored on platinum electrodes at high CO2 pressure. At 55 bar (5.5 MPa) of CO2 , the bulk electrolysis in both potentiostatic and galvanostatic regimes resulted in methanol production with Faradaic yields of up to 10 % for the first 5-10 C cm(-2) of charge passed. For longer electrolysis, the methanol concentration failed to increase proportionally and was limited to sub-ppm levels irrespective of biasing conditions and pyridine concentration. This limitation cannot be removed by electrode reactivation and/or pre-electrolysis and appears to be an inherent feature of the reduction process. In agreement with bulk electrolysis findings, the CV analysis supported by simulation indicated that hydrogen evolution is still the dominant electrode reaction in pyridine-containing electrolyte solution, even with an excess CO2 concentration in the solution. No prominent contribution from either a direct or coupled CO2 reduction was found. The results obtained suggest that the reduction of CO2 to methanol is a transient process that is largely decoupled from the electrode charge transfer. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Suppression of acetylpolyamine oxidase by selected AP-1 members regulates DNp73 abundance: mechanistic insights for overcoming DNp73-mediated resistance to chemotherapeutic drugs.

    Science.gov (United States)

    Bunjobpol, W; Dulloo, I; Igarashi, K; Concin, N; Matsuo, K; Sabapathy, K

    2014-08-01

    Enhanced resistance to chemotherapy has been correlated with high levels of Delta-Np73 (DNp73), an anti-apoptotic protein of the p53 tumor-suppressor family which inhibits the pro-apoptotic members such as p53 and TAp73. Although genotoxic drugs have been shown to induce DNp73 degradation, lack of mechanistic understanding of this process precludes strategies to enhance the targeting of DNp73 and improve treatment outcomes. Antizyme (Az) is a mediator of ubiquitin-independent protein degradation regulated by the polyamine biosynthesis pathway. We show here that acetylpolyamine oxidase (PAOX), a catabolic enzyme of this pathway, upregulates DNp73 levels by suppressing its degradation via the Az pathway. Conversely, downregulation of PAOX activity by siRNA-mediated knockdown or chemical inhibition leads to DNp73 degradation in an Az-dependent manner. PAOX expression is suppressed by several genotoxic drugs, via selected members of the activator protein-1 (AP-1) transcription factors, namely c-Jun, JunB and FosB, which are required for stress-mediated DNp73 degradation. Finally, chemical- and siRNA-mediated inhibition of PAOX significantly reversed the resistant phenotype of DNp73-overexpressing cancer cells to genotoxic drugs. Together, these data define a critical mechanism for the regulation of DNp73 abundance, and reveal that inhibition of PAOX could widen the therapeutic index of cytotoxic drugs and overcome DNp73-mediated chemoresistance in tumors.

  16. Improved methods in Agrobacterium-mediated transformation of almond using positive (mannose/pmi) or negative (kanamycin resistance) selection-based protocols.

    Science.gov (United States)

    Ramesh, Sunita A; Kaiser, Brent N; Franks, Tricia; Collins, Graham; Sedgley, Margaret

    2006-08-01

    A protocol for Agrobacterium-mediated transformation with either kanamycin or mannose selection was developed for leaf explants of the cultivar Prunus dulcis cv. Ne Plus Ultra. Regenerating shoots were selected on medium containing 15 muM kanamycin (negative selection), while in the positive selection strategy, shoots were selected on 2.5 g/l mannose supplemented with 15 g/l sucrose. Transformation efficiencies based on PCR analysis of individual putative transformed shoots from independent lines relative to the initial numbers of leaf explants tested were 5.6% for kanamycin/nptII and 6.8% for mannose/pmi selection, respectively. Southern blot analysis on six randomly chosen PCR-positive shoots confirmed the presence of the nptII transgene in each, and five randomly chosen lines identified to contain the pmi transgene by PCR showed positive hybridisation to a pmi DNA probe. The positive (mannose/pmi) and the negative (kanamycin) selection protocols used in this study have greatly improved transformation efficiency in almond, which were confirmed with PCR and Southern blot. This study also demonstrates that in almond the mannose/pmi selection protocol is appropriate and can result in higher transformation efficiencies over that of kanamycin/nptII selection protocols.

  17. Multiple parasites mediate balancing selection at two MHC class II genes in the fossorial water vole: insights from multivariate analyses and population genetics

    Czech Academy of Sciences Publication Activity Database

    Tollenaere, C.; Bryja, Josef; Galan, M.; Cadet, P.; Deter, J.; Chaval, Y.; Berthier, K.; Ribas Salvador, A.; Voutilainen, L.; Laakkonen, J.; Henttonen, H.; Cosson, J.-F.; Charbonnel, N.

    2008-01-01

    Roč. 21, č. 5 (2008), s. 1307-1320 ISSN 1010-061X EU Projects: European Commission(XE) 10284 - EDEN Institutional research plan: CEZ:AV0Z60930519 Keywords : co-inertia * DQA and DRB MHC gen es * immunogenetics * multivariate analysis * parasite-mediated balancing selection Subject RIV: EB - Gen etics ; Molecular Biology Impact factor: 3.471, year: 2008

  18. Ferromagnetic response of multiferroic TbMnO{sub 3} films mediated by epitaxial strain and chemical pressure

    Energy Technology Data Exchange (ETDEWEB)

    Izquierdo, J.; Morán, O., E-mail: omoranc@unal.edu.co [Universidad Nacional de Colombia, Campus Medellín, Departamento de Física, Laboratorio de Materiales Cerámicos y Vítreos, A.A. 568, Medellín Colombia (Colombia); Astudillo, A.; Bolaños, G. [Low Temperature Laboratory, Department of Physics, University of Cauca, Calle 5 No. 4-70, Popayán (Colombia); Arnache, O. [Instituto de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Calle 70 No. 52-21, A.A. 1226, Medellín (Colombia)

    2014-05-07

    High quality Tb{sub 1−x}Al{sub x}MnO{sub 3} (x = 0, 0.3) films have been grown under different values of compressive/tensile strain using (001)-oriented SrTiO{sub 3} and MgO substrates. The films were grown by means of rf sputtering at substrate temperature of 800  °C. X-ray diffraction analysis shows that films are single phase, preferentially oriented in the (111) and (122) directions for films deposited on SrTiO{sub 3} and MgO substrates, respectively. Although the TbMnO{sub 3} target shows antiferromagnetic order, the films deposited on both substrates show weak ferromagnetic phase at low temperature coexisting with the antiferromagnetic phase. The introduction of Al in the films clearly enhances their ferromagnetic behavior, improving the magnetic performance of this material. Indeed, M(H) measurements at 5 K show a well-defined hysteresis for films grown on both substrates. However, a stronger magnetic signal (larger values of remanence and coercive field) is observed for films deposited on MgO substrates. The chemical pressure generated by Al doping together with the substrate-induced strain seem to modify the subtle competition between magnetic interactions in the system. It is speculated that such modification could lead to a non-collinear magnetic state that may be tuned by strain modifications. This may be performed by varying the thickness of the films and/or considering other substrate materials.

  19. Was exposure to directly antiviral cytokines during primary infection an important selective pressure in the evolution of unique immune evasion strategies by viruses?

    Science.gov (United States)

    Lidbury, B A

    1994-08-01

    Different virus families are characterized by various immune evasion strategies. These viruses have co-evolved with an increasingly sophisticated mammalian immune system which has continually placed pressure on their continued survival. This paper proposes that exposure to directly antiviral cytokines, namely TNF and members of the IFN family, during inflammatory and early immune responses, exerted particularly strong selective pressures on viruses, and has had a critical influence on the development of viral immune evasion strategies and pathogenesis. In the context of antiviral cytokine activity, this report concentrates on two DNA virus families with contrasting pathogenic and immune evasion strategies, namely poxviruses and HSV.

  20. β-adrenergic Receptor Blocker ICI 118,551 Selectively Increases Intermediate-Conductance Calcium-Activated Potassium Channel (IKCa)-Mediated Relaxations in Rat Main Mesenteric Artery.

    Science.gov (United States)

    Ozkan, Melike Hacer; Uma, Serdar

    2017-12-26

    Endothelial IK C a and/or SK C a channels play an important role in the control of vascular tone by participating in endothelium-dependent relaxation. Whether β-AR antagonists, mainly used in hypertension, affect endothelial K C a channel function is unknown. In this study, we examined the effect of the β2-AR antagonist and inverse agonist ICI 118,551 on the IK C a /SK C a channel activity by assessing functional relaxation responses to several agonists that stimulate these channels. Mesenteric arterial rings isolated from male Sprague Dawley mounted to organ baths. Acetylcholine elicited IK C a - and SK C a -mediated relaxations that were abolished by TRAM-34 and apamin, respectively. ICI 118,551, which did not dilate the arteries per se, increased the IK C a -mediated relaxations, whereas SK C a -mediated relaxations remained unaltered. Same potentiating effect was also detected on the IK C a -mediated relaxations to carbachol and A23187, but not to NS309. Neither acetylcholine-induced nitric oxide-mediated relaxations nor SNP relaxations changed with ICI 118,551. The PKA inhibitor KT-5720, the selective β2-AR agonist salbutamol, the selective β2-AR antagonist butoxamine, the non-selective β-AR antagonist propranolol, and the inverse agonists carvedilol or nadolol failed to affect the IK C a -mediated relaxations. ICI 118,551-induced increase was not reversed by salbutamol or propranolol as well. Besides, low potassium-induced relaxations in endothelium-removed arteries remained the same in the presence of ICI 118,551. These data demonstrate a previously unrecognized action of ICI 118,551, the ability to potentiate endothelial IK C a channel-mediated vasodilation, through a mechanism independent of β2-AR antagonistic or inverse agonistic action. Instead, the enhancement of acetylcholine relaxation seems likely to occur by a mechanism secondary to endothelial calcium increase. © 2017 Nordic Association for the Publication of BCPT (former Nordic

  1. Thermodynamics of aqueous solutes at high temperatures and pressures: Application of the hydration theory and implications for fluid-mediated mass transfer

    Science.gov (United States)

    Sulak, M.; Dolejs, D.

    2012-04-01

    Magmatic activity and prograde devolatilization of subducting or underplating lithologies release large quantities of aqueous fluids that act as mass and heat transfer agents in the planetary interiors. Understanding of mineral-melt-fluid interactions is essential for evaluating the effects of fluid-mediated mass transport in subduction zones, collisional orogens as well as in igneous provinces. The thermodynamic properties of aqueous species were frequently described by the Helgeson-Kirkham-Flowers equation of state [1] but its utility is limited by inavailability of the solvent dielectric properties at high pressures and temperatures, and by decoupling of species-solvent mechanical and electrostatic interactions that cannot be separated within the Born theory. Systematic description of the hydration process in a Born-Haber cycle leads to the following thermochemical contributions: (i) thermodynamic properties of an unhydrated species, (ii) the pressure-volume work required to create a cavity within the solvent to accommodate the species, described by the scaled particle theory, (iii) entropic contribution related to changes in the solute's and the solvent's kinetic degrees of freedom, and (iv) contribution from the solute-solvent molecular interactions and corresponding rearrangement of the solvent molecules to form the hydration shell. Application of the spatial correlation functions [2, 3] results in apparent Gibbs energy of aqueous species, ΔaGi = a + bT + cTlnT + dP + eTlnρ + fTρlnρ, where athrough f represent constants related to standard thermodynamic properties of aqueous species (ΔfH, S, V, cP) and to solvent volumetric properties at 298.15 K and 1 bar (ρ, α, β etc.). In phase equilibrium calculations, the number of required parameters often reduces to four (c = f = 0) while noting that H2O density as the only solvent-related property is accurately known to extreme temperatures and pressures. The equation of state parameters were calibrated for 30

  2. Elevated hydrostatic pressure enhances the motility and enlarges the size of the lung cancer cells through aquaporin upregulation mediated by caveolin-1 and ERK1/2 signaling.

    Science.gov (United States)

    Kao, Y-C; Jheng, J-R; Pan, H-J; Liao, W-Y; Lee, C-H; Kuo, P-L

    2017-02-09

    The mechanical characteristics presented in cancer microenvironment are known to have pivotal roles in cancer metastasis, which accounts for the leading cause of death from malignant tumors. However, while a uniformly distributed high interstitial fluid pressure (IFP) is a common feature in solid tumors, the effects of high IFP on the motility and invasiveness of cancer cells remain obscure. Using cell-culture devices that simulated increased IFP conditions by applying hydrostatic pressure (HP) ranging from 0 to 20 mm Hg to the cells, we found that the elevated HPs increased the migration speeds, invasiveness, cell volume, filopodial number and aquaporin-1 (AQP1), Snail and vinculin expression levels, as well as phosphorylation of caveolin-1 and extracellular signal-regulated kinase1/2 (ERK1/2), in the lung cancer cells CL1-5 and A549. The increases of migration speed and cell volume correlated temporally with the increase of AQP1 expression. The elevated HP-induced migration acceleration was hindered by AQP1 knockdown using small interfering RNA (siRNA) transfection. Inhibition of ERK1/2 phosphorylation using the mitogen-activated protein kinase kinase inhibitor PD98059 abrogated the elevated HP-induced AQP1 upregulation and migration acceleration in the cancer cells. Caveolin-1 knockdown by siRNA transfection attenuated the HP-induced, ERK1/2-depedent AQP1 upregulation and migration acceleration. Further biochemical studies revealed that the caveolin-1 activation-driven ERK1/2 signaling is mediated by Akt1/2 phosphorylation. By contrast, the elevated HPs had negligible effects on the migration speed and volume of normal bronchial epithelial cells. These results disclose a novel mechanism relating high IFP to the invasiveness of cancer cells and highlight potential targets to impede cancer spreading.

  3. Ambient Temperature Hydrocarbon Selective Catalytic Reduction of NOx Using Atmospheric Pressure Nonthermal Plasma Activation of a Ag/Al2O3 Catalyst

    OpenAIRE

    Stere, Cristina E.; Adress, Wameedh; Burch, Robbie; Chansai, Sarayute; Goguet, Alexandre; Graham, William G.; De Rosa, Fabio; Palma, Vincenzo; Hardacre, Christopher

    2014-01-01

    Atmospheric pressure nonthermal-plasma-activated catalysis for the removal of NOx using hydrocarbon selective catalytic reduction has been studied utilizing toluene and n-octane as the hydrocarbon reductant. When the plasma was combined with a Ag/Al2O3 catalyst, a strong enhancement in activity was observed when compared with conventional thermal activation with high conversions of both. NOx and hydrocarbons obtained at temperature at temperature ≤250 °C, where the silver catalyst is normally...

  4. PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival

    Directory of Open Access Journals (Sweden)

    Amanda R. Panfil

    2015-12-01

    Full Text Available Human T-cell leukemia virus type-1 (HTLV-1 is a tumorigenic retrovirus responsible for development of adult T-cell leukemia/lymphoma (ATLL. This disease manifests after a long clinical latency period of up to 2–3 decades. Two viral gene products, Tax and HBZ, have transforming properties and play a role in the pathogenic process. Genetic and epigenetic cellular changes also occur in HTLV-1-infected cells, which contribute to transformation and disease development. However, the role of cellular factors in transformation is not completely understood. Herein, we examined the role of protein arginine methyltransferase 5 (PRMT5 on HTLV-1-mediated cellular transformation and viral gene expression. We found PRMT5 expression was upregulated during HTLV-1-mediated T-cell transformation, as well as in established lymphocytic leukemia/lymphoma cell lines and ATLL patient PBMCs. shRNA-mediated reduction in PRMT5 protein levels or its inhibition by a small molecule inhibitor (PRMT5i in HTLV-1-infected lymphocytes resulted in increased viral gene expression and decreased cellular proliferation. PRMT5i also had selective toxicity in HTLV-1-transformed T-cells. Finally, we demonstrated that PRMT5 and the HTLV-1 p30 protein had an additive inhibitory effect on HTLV-1 gene expression. Our study provides evidence for PRMT5 as a host cell factor important in HTLV-1-mediated T-cell transformation, and a potential target for ATLL treatment.

  5. From poor performance to success under stress: working memory, strategy selection, and mathematical problem solving under pressure.

    Science.gov (United States)

    Beilock, Sian L; Decaro, Marci S

    2007-11-01

    Two experiments demonstrate how individual differences in working memory (WM) impact the strategies used to solve complex math problems and how consequential testing situations alter strategy use. In Experiment 1, individuals performed multistep math problems under low- or high-pressure conditions and reported their problem-solving strategies. Under low-pressure conditions, the higher individuals' WM, the more likely they were to use computationally demanding algorithms (vs. simpler shortcuts) to solve the problems, and the more accurate their math performance. Under high-pressure conditions, higher WM individuals used simpler (and less efficacious) problem-solving strategies, and their performance accuracy suffered. Experiment 2 turned the tables by using a math task for which a simpler strategy was optimal (produced accurate performance in few problem steps). Now, under low-pressure conditions, the lower individuals' WM, the better their performance (the more likely they relied on a simple, but accurate, problem strategy). And, under pressure, higher WM individuals performed optimally by using the simpler strategies lower WM individuals employed. WM availability influences how individuals approach math problems, with the nature of the task performed and the performance environment dictating skill success or failure. PsycINFO Database Record (c) 2007 APA, all rights reserved.

  6. Natural selection acts in opposite ways on correlated hormonal mediators of prenatal maternal effects in a wild bird population

    NARCIS (Netherlands)

    Tschirren, Barbara; Postma, Erik; Gustafsson, Lars; Groothuis, Ton G. G.; Doligez, Blandine

    2014-01-01

    Maternal hormones are important mediators of prenatal maternal effects. Although many experimental studies have demonstrated their potency in shaping offspring phenotypes, we know remarkably little about their adaptive value. Using long-term data on a wild collared flycatcher (Ficedula albicollis)

  7. ApoE promotes hepatic selective uptake but not RCT due to increased ABCA1-mediated cholesterol efflux to plasma

    NARCIS (Netherlands)

    Annema, Wijtske; Dikkers, Arne; de Boer, Jan Freark; Gautier, Thomas; Rensen, Patrick C. N.; Rader, Daniel J.; Tietge, Uwe J. F.

    ApoE plays an important role in lipoprotein metabolism. This study investigated the effects of adenovirus-mediated human apoE overexpression (AdhApoE3) on sterol metabolism and in vivo reverse cholesterol transport (RCT). In wild-type mice, AdhApoE3 resulted in decreased HDL cholesterol levels and a

  8. The effect of marriage on young adult heavy drinking and its mediators: results from two methods of adjusting for selection into marriage.

    Science.gov (United States)

    Lee, Matthew R; Chassin, Laurie; Mackinnon, David

    2010-12-01

    This study tested the effect of marriage on young adult heavy drinking and tested whether this effect was mediated by involvement in social activities, religiosity, and self-control reasons for limiting drinking. The sample of 508 young adults was taken from an ongoing longitudinal study of familial alcoholism that over-sampled children of alcoholics (Chassin, Rogosch, & Barrera, 1991). In order to distinguish role socialization effects of marriage from confounding effects of role selection into marriage, analyses used both the analysis of covariance (ANCOVA) method and the change score method of adjusting for pre-marriage levels of heavy drinking and the mediators. Results showed role socialization effects of marriage on post-marriage declines in heavy drinking. This effect was mediated by involvement in social activities such that marriage predicted decreased involvement in social activities, which in turn predicted decreased heavy drinking. There were no statistically significant mediated effects of religiosity. The mediated effect of self-control reasons for limiting drinking was supported by the ANCOVA method only, and further investigation suggested that this result was detected erroneously due to violation of an assumption of the ANCOVA method that is not shared by the change score method. Findings from this study offer an explanation for the maturing out of heavy drinking that takes place for some individuals over the course of young adulthood. Methodologically, results suggest that the ANCOVA method should be employed with caution, and that the change score method is a viable approach to confirming results from the ANCOVA method. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  9. Intrarenal transfer of an intracellular fluorescent fusion of angiotensin II selectively in proximal tubules increases blood pressure in rats and mice

    Science.gov (United States)

    Li, Xiao C.; Cook, Julia L.; Rubera, Isabelle; Tauc, Michel; Zhang, Fan

    2011-01-01

    The present study tested the hypothesis that intrarenal adenoviral transfer of an intracellular cyan fluorescent fusion of angiotensin II (ECFP/ANG II) selectively in proximal tubules of the kidney increases blood pressure by activating AT1 (AT1a) receptors. Intrarenal transfer of ECFP/ANG II was induced in the superficial cortex of rat and mouse kidneys, and the sodium and glucose cotransporter 2 (sglt2) promoter was used to drive ECFP/ANG II expression selectively in proximal tubules. Intrarenal transfer of ECFP/ANG II induced a time-dependent, proximal tubule-selective expression of ECFP/ANG II in the cortex, which peaked at 2 wk and was sustained for 4 wk. ECFP/ANG II expression was low in the glomeruli and the entire medulla and was absent in the contralateral kidney or extrarenal tissues. At its peak of expression in proximal tubules at day 14, ANG II was increased by twofold in the kidney (P tubules (P kidney, and proximal tubule ANG II, or sodium excretion. These results provide evidence that proximal tubule-selective transfer of an intracellular ANG II fusion protein increases blood pressure by activating AT1a receptors and increasing sodium reabsorption in proximal tubules. PMID:21307128

  10. Significant Improvement Selected Mediators of Inflammation in Phenotypes of Women with PCOS after Reduction and Low GI Diet

    Directory of Open Access Journals (Sweden)

    Małgorzata Szczuko

    2017-01-01

    Full Text Available Many researchers suggest an increased risk of atherosclerosis in women with polycystic ovary syndrome. In the available literature, there are no studies on the mediators of inflammation in women with PCOS, especially after dietary intervention. Eicosanoids (HETE and HODE were compared between the biochemical phenotypes of women with PCOS (normal and high androgens and after the 3-month reduction diet. Eicosanoid profiles (9(S-HODE, 13(S-HODE, 5(S-HETE, 12(S-HETE, 15(S-HETE, 5(S-oxoETE, 16(R-HETE, 16(S-HETE and 5(S, 6(R-lipoxin A4, 5(S, 6(R, 15(R-lipoxin A4 were extracted from 0.5 ml of plasma using solid-phase extraction RP-18 SPE columns. The HPLC separations were performed on a 1260 liquid chromatograph. No significant differences were found in the concentration of analysed eicosanoids in phenotypes of women with PCOS. These women, however, have significantly lower concentration of inflammatory mediators than potentially healthy women from the control group. Dietary intervention leads to a significant (p<0.01 increase in the synthesis of proinflammatory mediators, reaching similar levels as in the control group. The development of inflammatory reaction in both phenotypes of women with PCOS is similar. The pathways for synthesis of proinflammatory mediators in women with PCOS are dormant, but can be stimulated through a reduction diet. Three-month period of lifestyle change may be too short to stimulate the pathways inhibiting inflammatory process.

  11. Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study

    Directory of Open Access Journals (Sweden)

    Handel Adam E

    2011-01-01

    Full Text Available Abstract Background Venous thromboembolism (VTE is a common complication during and after a hospital admission. Although it is mainly considered a complication of surgery, it often occurs in people who have not undergone surgery, with recent evidence suggesting that immune-mediated diseases may play a role in VTE risk. We, therefore, decided to study the risk of deep vein thrombosis (DVT and pulmonary embolism (PE in people admitted to hospital with a range of immune-mediated diseases. Methods We analysed databases of linked statistical records of hospital admissions and death certificates for the Oxford Record Linkage Study area (ORLS1:1968 to 1998 and ORLS2:1999 to 2008 and the whole of England (1999 to 2008. Rate ratios for VTE were determined, comparing immune-mediated disease cohorts with comparison cohorts. Results Significantly elevated risks of VTE were found, in all three populations studied, in people with a hospital record of admission for autoimmune haemolytic anaemia, chronic active hepatitis, dermatomyositis/polymyositis, type 1 diabetes mellitus, multiple sclerosis, myasthenia gravis, myxoedema, pemphigus/pemphigoid, polyarteritis nodosa, psoriasis, rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus. Rate ratios were considerably higher for some of these diseases than others: for example, for systemic lupus erythematosus the rate ratios were 3.61 (2.36 to 5.31 in the ORLS1 population, 4.60 (3.19 to 6.43 in ORLS2 and 3.71 (3.43 to 4.02 in the England dataset. Conclusions People admitted to hospital with immune-mediated diseases may be at an increased risk of subsequent VTE. Our findings need independent confirmation or refutation; but, if confirmed, there may be a role for thromboprophylaxis in some patients with these diseases.

  12. Significant Improvement Selected Mediators of Inflammation in Phenotypes of Women with PCOS after Reduction and Low GI Diet.

    Science.gov (United States)

    Szczuko, Małgorzata; Zapałowska-Chwyć, Marta; Maciejewska, Dominika; Drozd, Arleta; Starczewski, Andrzej; Stachowska, Ewa

    2017-01-01

    Many researchers suggest an increased risk of atherosclerosis in women with polycystic ovary syndrome. In the available literature, there are no studies on the mediators of inflammation in women with PCOS, especially after dietary intervention. Eicosanoids (HETE and HODE) were compared between the biochemical phenotypes of women with PCOS (normal and high androgens) and after the 3-month reduction diet. Eicosanoid profiles (9( S )-HODE, 13( S )-HODE, 5( S )-HETE, 12( S )-HETE, 15( S )-HETE, 5( S )-oxoETE, 16( R )-HETE, 16( S )-HETE and 5( S ), 6( R )-lipoxin A 4 , 5( S ), 6( R ), 15( R )-lipoxin A 4 ) were extracted from 0.5 ml of plasma using solid-phase extraction RP-18 SPE columns. The HPLC separations were performed on a 1260 liquid chromatograph. No significant differences were found in the concentration of analysed eicosanoids in phenotypes of women with PCOS. These women, however, have significantly lower concentration of inflammatory mediators than potentially healthy women from the control group. Dietary intervention leads to a significant ( p PCOS is similar. The pathways for synthesis of proinflammatory mediators in women with PCOS are dormant, but can be stimulated through a reduction diet. Three-month period of lifestyle change may be too short to stimulate the pathways inhibiting inflammatory process.

  13. Comprehensive characterization of glutamine synthetase-mediated selection for the establishment of recombinant CHO cells producing monoclonal antibodies

    DEFF Research Database (Denmark)

    Noh, Soo Min; Shin, Seunghyeon; Min Lee, Gyun

    2018-01-01

    and GS-knockout CHO). Regardless of the host cell lines used, the clones selected at 50 μM MSX had the lowest average specific growth rate and the highest average specific production rates of toxic metabolic wastes, lactate and ammonia. Unlike CHO-K1, high producing clones could be generated......To characterize a glutamine synthetase (GS)-based selection system, monoclonal antibody (mAb) producing recombinant CHO cell clones were generated by a single round of selection at various methionine sulfoximine (MSX) concentrations (0, 25, and 50 μM) using two different host cell lines (CHO-K1...... in the absence of MSX using GS-knockout CHO with an improved selection stringency. Regardless of the host cell lines used, the clones selected at various MSX concentrations showed no significant difference in the GS, heavy chain, and light chain gene copies (P > 0.05). Furthermore, there was no correlation...

  14. Effect of pressure on the selectivity of polymeric C18 and C30 stationary phases in reversed-phase liquid chromatography. Increased separation of isomeric fatty acid methyl esters, triacylglycerols, and tocopherols at high pressure.

    Science.gov (United States)

    Okusa, Kensuke; Iwasaki, Yuki; Kuroda, Ikuma; Miwa, Shohei; Ohira, Masayoshi; Nagai, Toshiharu; Mizobe, Hoyo; Gotoh, Naohiro; Ikegami, Tohru; McCalley, David V; Tanaka, Nobuo

    2014-04-25

    A high-density, polymeric C18 stationary phase (Inertsil ODS-P) or a polymeric C30 phase (Inertsil C30) provided improved resolution of the isomeric fatty acids (FAs), FA methyl esters (FAMEs), triacylglycerols (TAGs), and tocopherols with an increase in pressure of 20-70MPa in reversed-phase HPLC. With respect to isomeric C18 FAMEs with one cis-double bond, ODS-P phase was effective for recognizing the position of a double bond among petroselinic (methyl 6Z-octadecenoate), oleic (methyl 9Z-octadecenoate), and cis-vaccenic (methyl 11Z-octadecenoate), especially at high pressure, but the differentiation between oleic and cis-vaccenic was not achieved by C30 phase regardless of the pressure. A monomeric C18 phase (InertSustain C18) was not effective for recognizing the position of the double bond in monounsaturated FAME, while the separation of cis- and trans-isomers was achieved by any of the stationary phases. The ODS-P and C30 phases provided increased separation for TAGs and β- and γ-tocopherols at high pressure. The transfer of FA, FAME, or TAG molecules from the mobile phase to the ODS-P stationary phase was accompanied by large volume reduction (-30∼-90mL/mol) resulting in a large increase in retention (up to 100% for an increase of 50MPa) and improved isomer separation at high pressure. For some isomer pairs, the ODS-P and C30 provided the opposite elution order, and in each case higher pressure improved the separation. The two stationary phases showed selectivity for the isomers having rigid structures, but only the ODS-P was effective for differentiating the position of a double bond in monounsaturated FAMEs. The results indicate that the improved isomer separation was provided by the increased dispersion interactions between the solute and the binding site of the stationary phase at high pressure. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. A lover or a fighter? Opposing sexual selection pressures on men?s vocal pitch and facial hair

    OpenAIRE

    Saxton, Tamsin K.; Mackey, Lauren L.; McCarty, Kristofor; Neave, Nick

    2015-01-01

    The traditional assumption within the research literature on human sexually dimorphic traits has been that many sex differences have arisen from intersexual selection. More recently however, there has been a shift towards the idea that many male features, including for example male lower-pitched voices, and male beard growth, might have arisen predominantly through intrasexual selection: that is, to serve the purpose of male-male competition instead of mate attraction. In this study, using a ...

  16. Solubilities of selected organic electronic materials in pressurized hot water and estimations of aqueous solubilities at 298.15 K

    Czech Academy of Sciences Publication Activity Database

    Karásek, Pavel; Hohnová, Barbora; Planeta, Josef; Šťavíková, Lenka; Roth, Michal

    2013-01-01

    Roč. 90, č. 6 (2013), s. 2035-2040 ISSN 0045-6535 R&D Projects: GA ČR(CZ) GAP206/11/0138; GA ČR(CZ) GPP503/11/P523; GA ČR(CZ) GAP106/12/0522 Institutional support: RVO:68081715 Keywords : solubility * pressurized hot water * hole transport materials Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.499, year: 2013

  17. Surface-Energetic Heterogeneity of Nanoporous Solids for CO2 and CO Adsorption: The Key to an Adsorption Capacity and Selectivity at Low Pressures.

    Science.gov (United States)

    Kim, Moon Hyeon; Cho, Il Hum; Choi, Sang Ok; Lee, In Soo

    2016-05-01

    This study has been focused on surface energetic heterogeneity of zeolite (H-mordenite, "HM"), activated carbon ("RB2") and metal-organic framework family ("Z1200") materials and their isotherm features in adsorption of CO2 and CO at 25 degrees C and low pressures ≤ 850 Torr. The nanoporous solids showed not only distinctive shape of adsorption isotherms for CO2 with relatively high polarizability and quadrupole moment but also different capacities in the CO2 adsorption. These differences between the adsorbents could be well correlated with their surface nonuniformity. The most heterogeneous surfaces were found with the HM that gave the highest CO2 uptake at all pressures allowed, while the Z1200 consisted of completely homogeneous surfaces and even CO2 adsorption linearly increased with pressure. An intermediate character was indicated on the surface of RB2 and thus this sorbent possessed isotherm features between the HM and Z1200 in CO2 adsorption. Such different surface energetics was fairly consistent with changes in CO2/CO selectivity on the nanoporous adsorbents up to equilibrated pressures near 850 Torr.

  18. Cis and trans regulatory mechanisms control AP2-mediated B cell receptor endocytosis via select tyrosine-based motifs.

    Directory of Open Access Journals (Sweden)

    Kathleen Busman-Sahay

    Full Text Available Following antigen recognition, B cell receptor (BCR-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2 is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding YxxØ motifs, including four that are present within two immunoreceptor tyrosine-based activation motifs (ITAMs. Using a combination of in vitro and in situ approaches, we establish that the sole mediator of AP2-dependent BCR internalization is the membrane proximal ITAM YxxØ motif in CD79b, which is a major target of mutation in ABC DLBCL. In addition, we establish that BCR internalization can be regulated at a minimum of two different levels: regulation of YxxØ AP2 binding in cis by downstream ITAM-embedded DCSM and QTAT regulatory elements and regulation in trans by the partner cytoplasmic domain of the CD79 heterodimer. Beyond establishing the basic rules governing BCR internalization, these results illustrate an underappreciated role for ITAM residues in controlling clathrin-dependent endocytosis and highlight the complex mechanisms that control the activity of AP2 binding motifs in this receptor system.

  19. Curcumin induces ER stress-mediated apoptosis through selective generation of reactive oxygen species in cervical cancer cells.

    Science.gov (United States)

    Kim, Boyun; Kim, Hee Seung; Jung, Eun-Ji; Lee, Jung Yun; K Tsang, Benjamin; Lim, Jeong Mook; Song, Yong Sang

    2016-05-01

    Prolonged accumulation of misfolded or unfolded proteins caused by cellular stress, including oxidative stress, induces endoplasmic reticulum stress, which then activates an unfolded protein response (UPR). ER stress is usually maintained at higher levels in cancer cells as compared to normal cells due to altered metabolism in cancer. Here, we investigated whether curcumin is ER stress-mediated apoptosis in cervical cancer cells, and ROS increased by curcumin are involved in the process as an upstream contributor. Curcumin inhibited proliferation of cervical cancer cells (C33A, CaSki, HeLa, and ME180) and induced apoptotic cell death. Curcumin activated ER-resident UPR sensors, such as PERK, IRE-1α, and ATF6, and their downstream-signaling proteins in cervical cancer cells, but not in normal epithelial cells and peripheral blood mononuclear cells (PBMCs). CHOP, a key factor involved in ER stress-mediated apoptosis, was also activated by curcumin. CHOP decreased the ratio of anti-apoptotic protein Bcl-2 to pro-apoptotic protein Bax expression, and subsequently increased the apoptotic population of cervical cancer cells. Furthermore, curcumin elevated levels of intracellular reactive oxygen species (ROS) in cervical cancer cells, but not in normal epithelial cells. Scavenging ROS resulted in inhibition of ER stress and partially restored cell viability in curcumin-treated cancer cells. Collectively, these observations show that curcumin promotes ER stress-mediated apoptosis in cervical cancer cells through increase of cell type-specific ROS generation. Therefore, modulation of these differential responses to curcumin between normal and cervical cancer cells could be an effective therapeutic strategy without adverse effects on normal cells. © 2015 Wiley Periodicals, Inc.

  20. Magnetic properties of (Nd ,Ca )(Ba ,La ) C o2O5 +δ tuned by the site-selected charge doping, oxygen disorder, and hydrostatic pressure

    Science.gov (United States)

    Pietosa, J.; Kolesnik, S.; Puzniak, R.; Wisniewski, A.; Poudel, B.; Dabrowski, B.

    2017-11-01

    Comprehensive study of magnetic properties of the layer-ordered perovskites N d1 -xC axB a1 -yL ayC o2O5 +δ is presented as a function of the site-selected charge doping [ c =(x -y )/2 +δ -0.5 ,x ≤0.2 and y ≤0.1 ,0.07 0 ) and electron (c 0.5 , has a larger effect on antiferromagnetic phase than the charge doping. The temperature of metal-insulator transition TMIT was found practically unchanged by either charge doping or disorder. The application of hydrostatic pressure slightly suppressed TC and increased TN by stabilization of the antiferromagnetic phase with the largest observed value of d TN/d P =5.75 K /kbar . Complex magnetic behavior affected by hydrostatic pressure was accounted for by ferro- and antiferromagnetic interactions resulting from the charge separation and spin transitions.

  1. Determination of tetracycline antibiotics in fatty food samples by selective pressurized liquid extraction coupled with high-performance liquid chromatography and tandem mass spectrometry.

    Science.gov (United States)

    Jiao, Zhe; Zhang, Suling; Chen, Hongwei

    2015-01-01

    For the determination of trace residues of tetracycline antibiotics in fatty food samples, selective pressurized liquid extraction coupled with high-performance liquid chromatography and tandem mass spectrometry was applied in this study. Copper(II) isonicotinate was first used as online cleanup adsorbent in the selective pressurized liquid extraction process. The adsorbent to sample ratio, extraction temperature, extraction time, and recycle times, etc. were optimized. The tetracyclines in food samples of pork, chicken meat, and clam meat were detected by liquid chromatography with tandem mass spectrometry. Tetracycline was found at levels of 0.32 and 0.53 μg/g and oxytetracycline was found at 0.14 and 0.21 μg/g in chicken meat and clam meat, respectively, while chlorotetracycline and deoxytetracycline were below the detection limit. The detection limit (S/N = 3) for these four tetracyclines were from 0.2 to 3.3 ng/g, the recoveries were from 75.8 to 110.5%, and relative standard deviations were from 5.5 to 13.6%. Copper(II) isonicotinate showed a higher purification capacity than other cleanup adsorbents for extraction of antibiotics in fatty food and the recovery showed predominance compared with a pressurized liquid extraction method without adsorbent. The study demonstrated that copper(II) isonicotinate would be a promising cleanup adsorbent in pressurized liquid extraction for the analysis of trace organic pollutants in complicated samples. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Contrast Enhancement of Wavelength-Selective Detection of Mid-Infrared Using Localized Atmospheric-Pressure Plasma Treatment

    Science.gov (United States)

    Masuno, Katsuya; Tashiro, Kohji; Hori, Masaru; Kumagai, Shinya; Sasaki, Minoru

    2010-04-01

    A new processing method to enhance the signal contrast of a mid-infrared (MIR) detector integrated with a wavelength-selective function is studied. Using the hydrophilic characteristic of an IR absorber solution, an absorber material is selectively deposited onto a hydrophilically modified area over the hot junctions in the diaphragm of a thermopile detector. The hydrophilic modification of the chip-mounted detector is realized using localized atmospheric Ar + O2 plasma treatment through a stencil mask. Using a thermograph, we measured thermal distributions over a previously fabricated detector, whose absorber material is deposited using a manual manipulator without a position-selective mechanism, and the newly fabricated detector for comparison. The newly fabricated detector exhibited a larger temperature difference between hot and cold junctions than that of the previous detector. The detector has an increased signal contrast of 100% from the baseline at the absorption peak.

  3. Pressure to drink but not to smoke: disentangling selection and socialization in adolescent peer networks and peer groups.

    Science.gov (United States)

    Kiuru, Noona; Burk, William J; Laursen, Brett; Salmela-Aro, Katariina; Nurmi, Jari-Erik

    2010-12-01

    This paper examined the relative influence of selection and socialization on alcohol and tobacco use in adolescent peer networks and peer groups. The sample included 1419 Finnish secondary education students (690 males and 729 females, mean age 16 years at the outset) from nine schools. Participants identified three school friends and described their alcohol and tobacco use on two occasions one year apart. Actor-based models simultaneously examined changes in peer network ties and changes in individual behaviors for all participants within each school. Multi-level analyses examined changes in individual behaviors for adolescents entering new peer groups and adolescents in stable peer groups, both of which were embedded within the school-based peer networks. Similar results emerged from both analytic methods: Selection and socialization contributed to similarity of alcohol use, but only selection was a factor in tobacco use. Copyright © 2010 The Association for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  4. Effect of Selected Luting Agents on the Retention of CAD/CAM Zirconia Crowns under Cyclic Environmental Pressure

    OpenAIRE

    Leyla Sadighpour; Farideh Geramipanah; Akbar Fazel; Mahdi Allahdadi; Mohamad Javad KharaziFard

    2018-01-01

    Objectives: The aim of this study was to evaluate the retention strength of zirconia crowns luted with two types of resin cement under environmental pressure changes.Materials and Methods: Thirty zirconia crowns were fabricated by using computer-aided design/computer-aided manufacturing (CAD/CAM) system and were cemented by Panavia F2.0 (PAN), hand-mixed RelyX Unicem (UNH), or auto-mix RelyX Unicem Aplicap (UNA) cements on the corresponding extracted human molars. The samples were randomly di...

  5. Large scale selective synthesis of α-Co(OH){sub 2} and β-Co(OH){sub 2} nanosheets through a fluoride ions mediated phase transformation process

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Hongtao, E-mail: htcui@ytu.edu.cn [College of Chemistry and Chemical Engineering, Yantai University, 264005 Yantai (China); Zhao, Yunan; Ren, Wanzhong; Wang, Minmin; Liu, Yan [College of Chemistry and Chemical Engineering, Yantai University, 264005 Yantai (China)

    2013-06-15

    Highlights: ► α- and β-Co(OH){sub 2} nanosheets were selectively synthesized through an epoxide precipitation route. ► The phase purity of hydroxides depended on the reactivity of anions in reaction with epoxide. ► The polymorph type of cobalt hydroxide was controlled by concentration mediation of fluoride ions. ► The synthesis was carried out at mild conditions on large scale. -- Abstract: In this work, α-Co(OH){sub 2} and β-Co(OH){sub 2} nanosheets were selectively synthesized through an epoxide precipitation reaction under mediation of fluoride ions. The protonation and ring opening reaction of propylene oxide promoted the hydrolysis [Co(H{sub 2}O){sub 6}]{sup 2+} to form a mixed phase of α-Co(OH){sub 2} and Co{sub 2}(OH){sub 3}Cl in the condition of no existence of fluoride ions. Due to the enhanced hydrolysis of [Co(H{sub 2}O){sub 6}]{sup 2+} under function of fluoride ions, pure phases of α-Co(OH){sub 2} and β-Co(OH){sub 2} were formed respectively at different concentration of fluoride ions. The mild reaction condition of this route allows for large scale synthesis of cobalt hydroxide nanosheets, which is only limited by volume of the vessel used as reactor.

  6. Selective regulation of YB-1 mRNA translation by the mTOR signaling pathway is not mediated by 4E-binding protein.

    Science.gov (United States)

    Lyabin, D N; Ovchinnikov, L P

    2016-03-02

    The Y-box binding protein 1 (YB-1) is a key regulator of gene expression at the level of both translation and transcription. The mode of its action on cellular events depends on its subcellular distribution and the amount in the cell. So far, the regulatory mechanisms of YB-1 synthesis have not been adequately studied. Our previous finding was that selective inhibition of YB-1 mRNA translation was caused by suppression of activity of the mTOR signaling pathway. It was suggested that this event may be mediated by phosphorylation of the 4E-binding protein (4E-BP). Here, we report that 4E-BP alone can only slightly inhibit YB-1 synthesis both in the cell and in vitro, although it essentially decreases binding of the 4F-group translation initiation factors to mRNA. With inhibited mTOR kinase, the level of mRNA binding to the eIF4F-group factors was decreased, while that to 4E-BP1 was increased, as was observed for both mTOR kinase-sensitive mRNAs and those showing low sensitivity. This suggests that selective inhibition of translation of YB-1 mRNA, and probably some other mRNAs as well, by mTOR kinase inhibitors is not mediated by the action of the 4E-binding protein upon functions of the 4F-group translation initiation factors.

  7. Increased expression and secretion of recombinant hIFNγ through amino acid starvation-induced selective pressure on the adjacent HIS4 gene in Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Razaghi Ali

    2015-12-01

    Full Text Available Transcriptional co-regulation of adjacent genes has been observed for prokaryotic and eukaryotic organisms, alike. High levels of gene adjacency were also found in a wide variety of yeast species with a high frequency of co-regulated gene sets. The aim of this research was to study how selective pressure on the Histidinol dehydrogenase gene (HIS4, using amino acid starvation, affects the level of expression and secretion of the adjacent human interferon gamma gene (hIFNγ in the recombinant Pichia pastoris GS115 strain, a histidine-deficient mutant. hIFNγ was cloned into the pPIC9 vector adjacent to the HIS4 gene, a gene essential for histidine biosynthesis, which was then transformed into P. pastoris. The transformed P. pastoris was cultured under continuous amino acid starvation in amino acid-free minimal medium for ten days, with five inoculations into unspent medium every second day. Under these conditions, only successfully transformed cells (hIFNγ -HIS4+ are able to synthesise histidine and therefore thrive. As shown by ELISA, amino acid starvation-induced selective pressure on HIS4 improved expression and secretion of the adjacent hIFNγ by 55% compared to unchallenged cells. RT-qPCR showed that there was also a positive correlation between duration of amino acid starvation and increased levels of the hIFNγ RNA transcripts. According to these results, it is suggested that these adjacent genes (hIFNγ and HIS4 in the transformed P. pastoris are transcriptionally co-regulated and their expression is synchronised. To the best of the knowledge of the authors; this is the first study demonstrating that amino acid starvationinduced selective pressure on HIS4 can alter the regulation pattern of adjacent genes in P. pastoris.

  8. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells

    Science.gov (United States)

    Hepworth, Matthew R.; Fung, Thomas C.; Masur, Samuel H.; Kelsen, Judith R.; McConnell, Fiona M.; Dubrot, Juan; Withers, David R.; Hugues, Stephanie; Farrar, Michael A.; Reith, Walter; Eberl, Gerard; Baldassano, Robert N.; Laufer, Terri M.; Elson, Charles O.; Sonnenberg, Gregory F.

    2015-01-01

    Inflammatory CD4+ T cell responses to self or commensal bacteria underlie the pathogenesis of autoimmunity and inflammatory bowel disease (IBD), respectively. While selection of self-specific T cells in the thymus limits responses to tissue antigens, the mechanisms that control selection of commensal bacteria-specific T cells remain poorly understood. Here we demonstrate that group 3 innate lymphoid cell (ILC3)-intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells, and that MHCII+ ILC3s directly induce cell death of activated commensal bacteria-specific T cells. Further, MHCII on human colonic ILC3s was reduced in pediatric IBD patients. Collectively, these results define a selection pathway for commensal bacteria-specific CD4+ T cells in the intestine, and suggest that this process is dysregulated in human IBD. PMID:25908663

  9. Pressure to Drink but Not to Smoke: Disentangling Selection and Socialization in Adolescent Peer Networks and Peer Groups

    Science.gov (United States)

    Kiuru, Noona; Burk, William J.; Laursen, Brett; Salmela-Aro, Katariina; Nurmi, Jari-Erik

    2010-01-01

    This paper examined the relative influence of selection and socialization on alcohol and tobacco use in adolescent peer networks and peer groups. The sample included 1419 Finnish secondary education students (690 males and 729 females, mean age 16 years at the outset) from nine schools. Participants identified three school friends and described…

  10. Pressure to drink but not to smoke: Disentangling selection and socialization in adolescent peer networks and peer groups

    NARCIS (Netherlands)

    Kiuru, N.; Burk, W.J.; Laursen, B.; Salmela-Aro, K.; Nurmi, J.E.

    2010-01-01

    This paper examined the relative influence of selection and socialization on alcohol and tobacco use in adolescent peer networks and peer groups. The sample included 1419 Finnish secondary education students (690 males and 729 females, mean age 16 years at the outset) from nine schools. Participants

  11. Effect of growth rate and selection pressure on rates of transfer of an antibiotic resistance plasmid between E. coli strains

    NARCIS (Netherlands)

    Schuurmans, Jasper M.; van Hijum, Sacha A. F. T.; Piet, Jurgen R.; Händel, Nadine; Smelt, Jan; Brul, Stanley; ter Kuile, Benno H.

    2014-01-01

    Antibiotic resistance increases costs for health care and causes therapy failure. An important mechanism for spreading resistance is transfer of plasmids containing resistance genes and subsequent selection. Yet the factors that influence the rate of transfer are poorly known. Rates of plasmid

  12. The influence of selected containment structures on debris dispersal and transport following high pressure melt ejection from the reactor vessel

    International Nuclear Information System (INIS)

    Pilch, M.; Tarbell, W.W.; Brockmann, J.E.

    1988-09-01

    High pressure expulsion of molten core debris from the reactor pressure vessel may result in dispersal of the debris from the reactor cavity. In most plants, the cavity exits into the containment such that the debris impinges on structures. Retention of the debris on the structures may affect the further transport of the debris throughout the containment. Two tests were done with scaled structural shapes placed at the exit of 1:10 linear scale models of the Zion cavity. The results show that the debris does not adhere significantly to structures. The lack of retention is attributed to splashing from the surface and reentrainment in the gas flowing over the surface. These processes are shown to be applicable to reactor scale. A third experiment was done to simulate the annular gap between the reactor vessel and cavity wall. Debris collection showed that the fraction of debris exiting through the gap was greater than the gap-to-total flow area ratio. Film records indicate that dispersal was primarily by entrainment of the molten debris in the cavity. 29 refs., 36 figs., 11 tabs

  13. Effect of Selected Parameters of Pressure Die Casting on Quality of AlSi9Cu3 Castings

    Directory of Open Access Journals (Sweden)

    Pałyga Ł.

    2015-06-01

    Full Text Available This paper presents the results on the effects of die-casting process on the strength parameters of castings of the aluminium AlSi9Cu3 alloy belonging to the group of EN AB-46000, made on renovated high pressure die-casting machine. Specimens for quality testing were taken from the places of the casting most loaded during the service. The aim of a research was to prove how the new die-casting process control capabilities influence on the tensile strength of the cast material defined as a value of the breaking force of the specimens. It has been found that it is possible to specify a set of recommended settings valves of second (II and third (III phase, which are responsible for filling the metal mould on die-casting pressure machine. From the point of view of the finished cast element, it was noticed that exceeding the prescribed values of valve settings does not bring further benefits and even causes unnecessary overload and reduce the durability of the mold. Moreover, it was noticed that reduction of the predetermined setting of the second phase (II valve leads to the formation of casting defects again.

  14. An efficient gene disruption method using a positive-negative split-selection marker and Agrobacterium tumefaciens-mediated transformation for Nomuraea rileyi.

    Science.gov (United States)

    Su, Yu; Wang, Zhongkang; Shao, Changwen; Luo, Yuanli; Wang, Li; Yin, Youping

    2018-01-16

    Targeted gene disruption via Agrobacterium tumefaciens-mediated transformation (ATMT) and homologous recombination is the most common method used to identify and investigate the functions of genes in fungi. However, the gene disruption efficiency of this method is low due to ectopic integration. In this study, a high-efficiency gene disruption strategy based on ATMT and the split-marker method was developed for use in Nomuraea rileyi. The β-glucuronidase (gus) gene was used as a negative selection marker to facilitate the screening of putative transformants. We assessed the efficacy of this gene disruption method using the NrCat1, NrCat4, and NrPex16 genes and found that the targeting efficiency was between 36.2 and 60.7%, whereas the targeting efficiency using linear cassettes was only 1.0-4.2%. The efficiency of negative selection assays was between 64.1 and 82.3%. Randomly selected deletion mutants exhibited a single copy of the hph cassette. Therefore, high-throughput gene disruption could be possible using the split-marker method and the majority of ectopic integration transformants can be eliminated using negative selection markers. This study provides a platform to study the function of genes in N. rileyi.

  15. Positive selection pressure introduces secondary mutations at Gag cleavage sites in human immunodeficiency virus type 1 harboring major protease resistance mutations

    DEFF Research Database (Denmark)

    Banke, S.; Lillemark, M.R.; Gerstoft, J.

    2009-01-01

    Human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) specifically target the HIV-1 protease enzyme. Mutations in the enzyme can result in PI resistance (termed PI mutations); however, mutations in the HIV-1 gag region, the substrate for the protease enzyme, might also lead to PI...... resistance. We analyzed gag and pol sequence data from the following 313 HIV-1-infected patients: 160 treatment-naive patients, 93 patients failing antiretroviral treatment that included a PI (with no major PI mutations), and 60 patients failing antiretroviral treatment that included a PI (with major PI...... that positive selection pressure was the driving evolutionary force for the gag region in all three patient groups. An increase in positive selection was observed in gag cleavage site regions p7/p1/p6 only after the acquisition of major PI mutations, suggesting that amino acids in gag cleavage sites under...

  16. Different Patterns of pfcrt and pfmdr1 Polymorphisms in P. falciparum Isolates from Nigeria and Brazil: The Potential Role of Antimalarial Drug Selection Pressure

    Science.gov (United States)

    Gbotosho, Grace O.; Folarin, Onikepe A.; Bustamante, Carolina; Pereira da Silva, Luis Hildebrando; Mesquita, Elieth; Sowunmi, Akintunde; Zalis, Mariano G.; Oduola, Ayoade M. J.; Happi, Christian T.

    2012-01-01

    The effect of antimalarial drug selection on pfcrt and pfmdr1 polymorphisms in Plasmodium falciparum isolates from two distinct geographical locations was determined in 70 and 18 P. falciparum isolates from Nigeria and Brazil, respectively, using nested polymerase chain reaction and direct DNA sequencing approaches. All isolates from Brazil and 72% from Nigeria harbored the mutant SVMNT and CVIET pfcrt haplotype, respectively. The pfcrt CVMNT haplotype was also observed in (7%) of the Nigerian samples. One hundred percent (100%) and 54% of the parasites from Brazil and Nigeria, respectively, harbored wild-type pfmdr1Asn86. We provide first evidence of emergence of the CVMNT haplotype in West Africa. The high prevalence of pfcrt CVIET and SVMNT haplotypes in Nigeria and Brazil, respectively, is indicative of different selective pressure by chloroquine and amodiaquine. Continuous monitoring of pfcrt SVMNT haplotype is required in endemic areas of Africa, where artesunate-amodiaquine combination is used for treatment of acute uncomplicated malaria. PMID:22302850

  17. Selective Killing Effects of Cold Atmospheric Pressure Plasma with NO Induced Dysfunction of Epidermal Growth Factor Receptor in Oral Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Jung-Hwan Lee

    Full Text Available The aim of this study is to investigate the effects of cold atmospheric pressure plasma (CAP-induced radicals on the epidermal growth factor receptor (EGFR, which is overexpressed by oral squamous cell carcinoma, to determine the underlying mechanism of selective killing. CAP-induced highly reactive radicals were observed in both plasma plume and cell culture media. The selective killing effect was observed in oral squamous cell carcinoma compared with normal human gingival fibroblast. Degradation and dysfunction of EGFRs were observed only in the EGFR-overexpressing oral squamous cell carcinoma and not in the normal cell. Nitric oxide scavenger pretreatment in cell culture media before CAP treatment rescued above degradation and dysfunction of the EGFR as well as the killing effect in oral squamous cell carcinoma. CAP may be a promising cancer treatment method by inducing EGFR dysfunction in EGFR-overexpressing oral squamous cell carcinoma via nitric oxide radicals.

  18. Selectivity of plasma membrane calcium ATPase (PMCA)-mediated extrusion of toxic divalent cations in vitro and in cultured cells.

    Science.gov (United States)

    Ferreira-Gomes, Mariela S; Mangialavori, Irene C; Ontiveros, Mallku Q; Rinaldi, Debora E; Martiarena, Jorge; Verstraeten, Sandra V; Rossi, Juan Pablo F C

    2018-01-01

    In the recent years, the toxicity of certain divalent cations has been associated with the alteration of intracellular Ca 2+ homeostasis. Among other mechanisms, these cations may affect the functionality of certain Ca 2+ -binding proteins and/or Ca 2+ pumps. The plasma membrane calcium pump (PMCA) maintains Ca 2+ homeostasis in eukaryotic cells by mediating the efflux of this cation in a process coupled to ATP hydrolysis. The aim of this work was to investigate both in vitro and in cultured cells if other divalent cations (Sr 2+ , Ba 2+ , Co 2+ , Cd 2+ , Pb 2+ or Be 2+ ) could be transported by PMCA. Current results indicate that both purified and intact cell PMCA transported Sr 2+ with kinetic parameters close to those of Ca 2+ transport. The transport of Pb 2+ and Co 2+ by purified PMCA was, respectively, 50 and 75% lower than that of Ca 2+ , but only Co 2+ was extruded by intact cells and to a very low extent. In contrast, purified PMCA-but not intact cell PMCA-transported Ba 2+ at low rates and only when activated by limited proteolysis or by phosphatidylserine addition. Finally, purified PMCA did not transport Cd 2+ or Be 2+ , although minor Be 2+ transport was measured in intact cells. Moreover, Cd 2+ impaired the transport of Ca 2+ through various mechanisms, suggesting that PMCA may be a potential target of Cd 2+ -mediated toxicity. The differential capacity of PMCA to transport these divalent cations may have a key role in their detoxification, limiting their noxious effects on cell homeostasis.

  19. Wild cyclic voles maintain high neutral and MHC diversity without strong evidence for parasite-mediated selection

    Czech Academy of Sciences Publication Activity Database

    Winternitz, Jamie Caroline; Wares, J. P.; Yabsley, M. J.; Altizer, S.

    2014-01-01

    Roč. 28, č. 5 (2014), s. 957-975 ISSN 0269-7653 Institutional support: RVO:68081766 Keywords : Major histocompatibility complex * Host-parasite relationship * Balancing selection * Microtus montanus * Cestodes * Eimeria * Microsatellites Subject RIV: EG - Zoology Impact factor: 2.517, year: 2014

  20. Mediation of oviposition site selection in the African malaria mosquito Anopheles gambiae (Diptera: Culicidae) by semiochemicals of microbial origin

    NARCIS (Netherlands)

    Sumba, L.A.; Guda, T.O.; Deng, A.L.; Hassanali, A.; Beier, J.C.; Knols, B.G.J.

    2004-01-01

    Laboratory studies were carried out to investigate the role of larval habitat-derived microorganisms in the production of semiochemicals for oviposition site selection by Anopheles gambiae Giles sensu stricto mosquitoes. Dual-choice bioassays with gravid females were conducted in standard mosquito

  1. Development of Selectable Marker-Free Transgenic Rice Plants with Enhanced Seed Tocopherol Content through FLP/FRT-Mediated Spontaneous Auto-Excision.

    Directory of Open Access Journals (Sweden)

    Hee-Jong Woo

    Full Text Available Development of marker-free transgenic plants is a technical alternative for avoiding concerns about the safety of selectable marker genes used in genetically modified (GM crops. Here, we describe the construction of a spontaneous self-excision binary vector using an oxidative stress-inducible modified FLP/FRT system and its successful application to produce marker-free transgenic rice plants with enhanced seed tocopherol content. To generate selectable marker-free transgenic rice plants, we constructed a binary vector using the hpt selectable marker gene and the rice codon-optimized FLP (mFLP gene under the control of an oxidative stress-inducible promoter between two FRT sites, along with multiple cloning sites for convenient cloning of genes of interest. Using this pCMF binary vector with the NtTC gene, marker-free T1 transgenic rice plants expressing NtTC were produced by Agrobacterium-mediated stable transformation using hygromycin as a selective agent, followed by segregation of selectable marker genes. Furthermore, α-, γ-, and total tocopherol levels were significantly increased in seeds of the marker-free transgenic TC line compared with those of wild-type plants. Thus, this spontaneous auto-excision system, incorporating an oxidative stress-inducible mFLP/FRT system to eliminate the selectable marker gene, can be easily adopted and used to efficiently generate marker-free transgenic rice plants. Moreover, nutritional enhancement of rice seeds through elevation of tocopherol content coupled with this marker-free strategy may improve human health and public acceptance of GM rice.

  2. Development of Selectable Marker-Free Transgenic Rice Plants with Enhanced Seed Tocopherol Content through FLP/FRT-Mediated Spontaneous Auto-Excision.

    Science.gov (United States)

    Woo, Hee-Jong; Qin, Yang; Park, Soo-Yun; Park, Soon Ki; Cho, Yong-Gu; Shin, Kong-Sik; Lim, Myung-Ho; Cho, Hyun-Suk

    2015-01-01

    Development of marker-free transgenic plants is a technical alternative for avoiding concerns about the safety of selectable marker genes used in genetically modified (GM) crops. Here, we describe the construction of a spontaneous self-excision binary vector using an oxidative stress-inducible modified FLP/FRT system and its successful application to produce marker-free transgenic rice plants with enhanced seed tocopherol content. To generate selectable marker-free transgenic rice plants, we constructed a binary vector using the hpt selectable marker gene and the rice codon-optimized FLP (mFLP) gene under the control of an oxidative stress-inducible promoter between two FRT sites, along with multiple cloning sites for convenient cloning of genes of interest. Using this pCMF binary vector with the NtTC gene, marker-free T1 transgenic rice plants expressing NtTC were produced by Agrobacterium-mediated stable transformation using hygromycin as a selective agent, followed by segregation of selectable marker genes. Furthermore, α-, γ-, and total tocopherol levels were significantly increased in seeds of the marker-free transgenic TC line compared with those of wild-type plants. Thus, this spontaneous auto-excision system, incorporating an oxidative stress-inducible mFLP/FRT system to eliminate the selectable marker gene, can be easily adopted and used to efficiently generate marker-free transgenic rice plants. Moreover, nutritional enhancement of rice seeds through elevation of tocopherol content coupled with this marker-free strategy may improve human health and public acceptance of GM rice.

  3. Anomalous ionic conductivity of Sc sub 2 (WO sub 4) sub 3 mediated by structural changes at high pressures and temperatures

    CERN Document Server

    Secco, R A; Imanaka, N; Adachi, G

    2002-01-01

    The ionic conductivity of Sc sub 2 (WO sub 4) sub 3 at 400 deg. C shows a normal decrease with increase in pressure up to 2.9 GPa but then increases anomalously at pressures up to 4.3 GPa. Synchrotron in situ x-ray diffraction results show that Sc sub 2 (WO sub 4) sub 3 undergoes pressure-induced amorphization at pressures coincident with the reversal in conductivity behaviour. The loss of crystal structure at high pressure may be associated with the property of negative thermal expansion in Sc sub 2 (WO sub 4) sub 3.

  4. Effect of Selected Luting Agents on the Retention of CAD/CAM Zirconia Crowns under Cyclic Environmental Pressure

    Directory of Open Access Journals (Sweden)

    Leyla Sadighpour

    2018-02-01

    Full Text Available Objectives: The aim of this study was to evaluate the retention strength of zirconia crowns luted with two types of resin cement under environmental pressure changes.Materials and Methods: Thirty zirconia crowns were fabricated by using computer-aided design/computer-aided manufacturing (CAD/CAM system and were cemented by Panavia F2.0 (PAN, hand-mixed RelyX Unicem (UNH, or auto-mix RelyX Unicem Aplicap (UNA cements on the corresponding extracted human molars. The samples were randomly divided into three groups according to the cement type. After 3000 thermal cycles, the cemented crowns were subjected to 24 pressure cycles (0 to 5 atmospheres. The retention force (N of the specimens was measured in a universal testing machine. To normalize the retentive force, the recorded force was divided by the surface area of each tooth for measuring the retentive strength (MPa. The mean retention strengths (and forces of the groups were compared by using one-way analysis of variance (ANOVA and Tukey’s honest significant difference (HSD test (α=0.05. The failure modes were also examined by using a stereomicroscope.Results: The retention values related to the evaluated resin cements were significantly different; the UNA group showed the highest retention strength (6.45±0.35 MPa followed by the UNH (4.99±0.47 MPa and PAN (4.45±0.39 MPa, P<0.001 groups. The adhesive failure mode was predominant in all the groups.Conclusions: The choice of resin cements and their mixing methods, which lead to differences in porosity, may affect the retention strength of zirconia crowns.

  5. Aquaporins in the wild: natural genetic diversity and selective pressure in the PIP gene family in five Neotropical tree species.

    Science.gov (United States)

    Audigeos, Delphine; Buonamici, Anna; Belkadi, Laurent; Rymer, Paul; Boshier, David; Scotti-Saintagne, Caroline; Vendramin, Giovanni G; Scotti, Ivan

    2010-06-29

    Tropical trees undergo severe stress through seasonal drought and flooding, and the ability of these species to respond may be a major factor in their survival in tropical ecosystems, particularly in relation to global climate change. Aquaporins are involved in the regulation of water flow and have been shown to be involved in drought response; they may therefore play a major adaptive role in these species. We describe genetic diversity in the PIP sub-family of the widespread gene family of Aquaporins in five Neotropical tree species covering four botanical families. PIP Aquaporin subfamily genes were isolated, and their DNA sequence polymorphisms characterised in natural populations. Sequence data were analysed with statistical tests of standard neutral equilibrium and demographic scenarios simulated to compare with the observed results. Chloroplast SSRs were also used to test demographic transitions. Most gene fragments are highly polymorphic and display signatures of balancing selection or bottlenecks; chloroplast SSR markers have significant statistics that do not conform to expectations for population bottlenecks. Although not incompatible with a purely demographic scenario, the combination of all tests tends to favour a selective interpretation of extant gene diversity. Tropical tree PIP genes may generally undergo balancing selection, which may maintain high levels of genetic diversity at these loci. Genetic variation at PIP genes may represent a response to variable environmental conditions.

  6. Analysis of polymorphisms and selective pressures on ama1 gene in Plasmodium knowlesi isolates from Sabah, Malaysia.

    Science.gov (United States)

    Chua, Chuen Yang; Lee, Ping Chin; Lau, Tiek Ying

    2017-09-01

    The apical membrane antigen-1 (AMA-1) of Plasmodium spp. is a merozoite surface antigen that is essential for the recognition and invasion of erythrocytes. Polymorphisms occurring in this surface antigen will cause major obstacles in developing effective malaria vaccines based on AMA-1. The objective of this study was to characterize ama1 gene in Plasmodium knowlesi isolates from Sabah. DNA was extracted from blood samples collected from Keningau, Kota Kinabalu and Kudat. The Pkama1 gene was amplified using nested PCR and subjected to bidirectional sequencing. Analysis of DNA sequence revealed that most of the nucleotide polymorphisms were synonymous and concentrated in domain I of PkAMA-1. Forteen haplotypes were identified based on amino acid variations and haplotype K5 was the most common haplotype. d N /d S ratios implied that purifying selection was prevalent in Pkama1 gene. Fu and Li's D and F values further provided evidence of negative selection acting on domain II of Pkama1. Lownucleotide diversitywas also detected for the Pkama1 sequences,which is similar to reports on Pkama1 from Peninsular Malaysia and Sarawak. The presence of purifying selection and low nucleotide diversity indicated that domain II of Pkama1 can be used as a target for vaccine development.

  7. Aquaporins in the wild: natural genetic diversity and selective pressure in the PIP gene family in five Neotropical tree species

    Directory of Open Access Journals (Sweden)

    Vendramin Giovanni G

    2010-06-01

    Full Text Available Abstract Background Tropical trees undergo severe stress through seasonal drought and flooding, and the ability of these species to respond may be a major factor in their survival in tropical ecosystems, particularly in relation to global climate change. Aquaporins are involved in the regulation of water flow and have been shown to be involved in drought response; they may therefore play a major adaptive role in these species. We describe genetic diversity in the PIP sub-family of the widespread gene family of Aquaporins in five Neotropical tree species covering four botanical families. Results PIP Aquaporin subfamily genes were isolated, and their DNA sequence polymorphisms characterised in natural populations. Sequence data were analysed with statistical tests of standard neutral equilibrium and demographic scenarios simulated to compare with the observed results. Chloroplast SSRs were also used to test demographic transitions. Most gene fragments are highly polymorphic and display signatures of balancing selection or bottlenecks; chloroplast SSR markers have significant statistics that do not conform to expectations for population bottlenecks. Although not incompatible with a purely demographic scenario, the combination of all tests tends to favour a selective interpretation of extant gene diversity. Conclusions Tropical tree PIP genes may generally undergo balancing selection, which may maintain high levels of genetic diversity at these loci. Genetic variation at PIP genes may represent a response to variable environmental conditions.

  8. Relatively high antibiotic resistance among heterotrophic bacteria from arctic fjord sediments than water - Evidence towards better selection pressure in the fjord sediments

    Science.gov (United States)

    Hatha, A. A. Mohamed; Neethu, C. S.; Nikhil, S. M.; Rahiman, K. M. Mujeeb; Krishnan, K. P.; Saramma, A. V.

    2015-12-01

    The objective of this study was to determine the prevalence of antibiotic resistance among aerobic heterotrophic bacteria and coliform bacteria from water and sediment of Kongsfjord. The study was based on the assumption that arctic fjord environments are relatively pristine and offer very little selection pressure for drug resistant mutants. In order to test the hypothesis, 200 isolates belonging to aerobic heterotrophic bacteria and 114 isolates belonging to coliforms were tested against 15 antibiotics belonging to 5 different classes such as beta lactams, aminoglycosides, quinolones, sulpha drugs and tetracyclines. Resistance to beta lactam and extended spectrum beta lactam (ESBL) antibiotics was considerably high and they found to vary significantly (p coliform bacteria. Though the coliforms showed significantly high level of antibiotic resistance against ESBL's extent and diversity of antibiotic resistance (as revealed by multiple antibiotic resistance index and resistance patterns), was high in the aerobic heterotrophic bacteria. Most striking observation was that isolates from fjord sediments (both heterotrophic bacteria and coliforms) in general showed relatively high prevalence of antibiotic resistance against most of the antibiotics tested, indicating to better selection pressure for drug resistance mutants in the fjord sediments.

  9. Edaphic Selection Pressures as Drivers of Contrasting White Spruce Ectomycorrhizal Fungal Community Structure and Diversity in the Canadian Boreal Forest of Abitibi-Témiscamingue Region

    Science.gov (United States)

    Nadeau, Martin B.; P. Khasa, Damase

    2016-01-01

    Little is known about edaphic selection pressures as drivers of contrasting white spruce ectomycorrhizal fungal community structure and diversity in the Canadian boreal forest. We hypothesized that community composition differs among the four sites sampled–nursery, mining site, forest edge, and natural forest. Ectomycorrhizal (ECM) fungal community structure and diversity was studied at the four locations with soil fertility gradient through morpho-molecular and phylogenetic analyses in relationships with rhizospheric soil chemical properties. 41 different species were identified. Mining site had a significantly different species composition than the surrounding environments. Soil pH and percentage of roots colonized by ECM fungi increased while soil P, N, Fe, C, K, Mg, Al, Ca, and Na contents declined across the soil fertility gradient: nursery → natural forest → forest edge → mining site. Contrary to the preference of acid soils by ECM fungi, a few ecologically adapted to high pH, poor soil chemical fertility, and low organic matter content colonize white spruce roots on the non-acidogenic mining site, allowing natural regeneration of white spruce seedlings. Other ECM fungi are adapted to high fertigation level of commercial nursery. This study clearly shows the contrasting difference in white spruce ectomycorrhizal fungal community structure and diversity driven by edaphic selection pressures. PMID:27835688

  10. The Heterogeneity of Mutational Tolerance in a Protein is Dependent on the Strength of Selective Pressure Correlating with Sectors of Co-evolving Residues

    Science.gov (United States)

    Stiffler, Michael; Ranganathan, Rama

    2011-03-01

    Proteins are capable of tolerating mutations at many positions while still maintaining fold and function. Previous studies have failed to consider how tolerance to random mutagenesis might depend on the strength of selective pressure. To examine this, we measured the fitness of every single point mutation of TEM-1 beta-lactamase across a range of ampicillin concentrations utilizing a novel application of deep-sequencing. We found that the relative mutational robustness between positions varied considerably with respect to ampicillin concentration: at a low ampicillin concentration only a few positions are intolerant of mutations, while at a higher ampicillin concentration many additional positions are as equally intolerant of mutations. Using an analytic method termed statistical coupling analysis (SCA) to measure the co-variation between all positions in a sequence alignment of beta-lactamases revealed sectors of co-evolving positions associated with groups of residues having increased sensitivity to mutagenesis at either low or high ampicillin concentrations. Our findings suggest that nature has ``designed'' proteins to be robust to random mutagenesis by loading the constraints for fitness on discrete networks of co-evolving positions depending on the strength of selective pressure.

  11. Edaphic Selection Pressures as Drivers of Contrasting White Spruce Ectomycorrhizal Fungal Community Structure and Diversity in the Canadian Boreal Forest of Abitibi-Témiscamingue Region.

    Science.gov (United States)

    Nadeau, Martin B; P Khasa, Damase

    2016-01-01

    Little is known about edaphic selection pressures as drivers of contrasting white spruce ectomycorrhizal fungal community structure and diversity in the Canadian boreal forest. We hypothesized that community composition differs among the four sites sampled-nursery, mining site, forest edge, and natural forest. Ectomycorrhizal (ECM) fungal community structure and diversity was studied at the four locations with soil fertility gradient through morpho-molecular and phylogenetic analyses in relationships with rhizospheric soil chemical properties. 41 different species were identified. Mining site had a significantly different species composition than the surrounding environments. Soil pH and percentage of roots colonized by ECM fungi increased while soil P, N, Fe, C, K, Mg, Al, Ca, and Na contents declined across the soil fertility gradient: nursery → natural forest → forest edge → mining site. Contrary to the preference of acid soils by ECM fungi, a few ecologically adapted to high pH, poor soil chemical fertility, and low organic matter content colonize white spruce roots on the non-acidogenic mining site, allowing natural regeneration of white spruce seedlings. Other ECM fungi are adapted to high fertigation level of commercial nursery. This study clearly shows the contrasting difference in white spruce ectomycorrhizal fungal community structure and diversity driven by edaphic selection pressures.

  12. Selection of Optimum Strategies for the Fabrication of Plant-Mediated Metal Nanoparticles: Emerging Problems in Sustainability.

    Science.gov (United States)

    Din, Muhammad Imran; Rani, Aneela

    2018-03-21

    The green fabrication of nanoparticles (NPs) by using plants as reducing and capping agents involves energy efficient, less toxic, safer and simpler pathways. These pathways have been related to the rational use of numerous substances in fabrication of NPs and synthetic strategies, which have been mainly discussed in this article. The subject matter of this review is to discuss how a chemist can follow the green chemistry principles in terms of selection of substances and protocols used for NPs fabrication. Furthermore, it describes how a researcher can modify the physical properties of NPs by varying the reaction conditions. In short, this review article provides a scheme for the synthesis of NPs from selection of suitable plant to characterization of formed NPs by employing green chemistry.

  13. Kupffer cell depletion attenuates leptin-mediated methoxamine-stimulated portal perfusion pressure and thromboxane A2 release in a rodent model of NASH-cirrhosis.

    Science.gov (United States)

    Yang, Ying-Ying; Huang, Yi-Tsau; Tsai, Tung-Hu; Hou, Ming-Chih; Lee, Fa-Yauh; Lee, Shou-Dong; Lin, Han-Chieh

    2012-12-01

    Cirrhotic portal hypertension is characterized by increased hepatic oxidative stress, AA (arachidonic acid)-derived TXA(2) (thromboxane A(2)) release and exaggerated hepatic response to the α-adrenergic agonist MTX (methoxamine). Besides promoting hepatic fibrosis, the role of hyperleptinaemia in the modulation of vascular response in NASH (non-alcoholic steatohepatitis) rat livers remains unknown. The aim of the present study was to explore the possible links between hyperleptinaemia and the disarrangement in the hepatic microcirculation. NASH-cirrhosis with hyperleptinaemia was induced in lean rats by feeding with an HF/MCD (high-fat/methionine-choline-deficient) diet. Portal haemodynamics, various substances, protein and mRNA expression and PUFA (polyunsaturated fatty acid) composition were measured. Finally, the effects of leptin pre-infusion on TXA(2) release and concentration-PPP (portal perfusion pressure) curves in response to MTX were evaluated by simultaneously pre-treatment with the Kupffer cell inactivators GdCl(3) (gadolinium chloride) or EC (encapsulated clodronate), the TXS (TXA(2) synthase) inhibitor furegrelate, the TP receptor (TXA(2) receptor) antagonist SQ29548 and the dual TXS/TP receptor antagonist BM567. In HF/MCD+leptin-lean rats, cirrhosis-induced PPP and MTX hyper-responsiveness were associated with increased hepatic TXA(2) production, TBARS (thiobarbituric acid-reacting substances) levels and the AA (arachidonic acid)/n-3 PUFA ratio, and up-regulation of hepatic leptin, FAS (fatty acid synthase), NADPH oxidase subunits, TXS, TP receptor, TGFβ(1) (transforming growth factor β(1)) proteins and mRNAs. Pre-infusion of leptin significantly enhanced MTX-stimulated PPP elevation and TXA(2) release, which were attenuated by GdCl(3) and EC pre-treatment. Concomitantly pre-incubation with BM567, but not furegrelate or SQ29548, significantly abolished the leptin-enhanced MTX-stimulated increase in PPP in NASH-cirrhotic rats. Hyperleptinaemia

  14. A new method to increase selectivity of transglutaminase mediated PEGylation of salmon calcitonin and human growth hormone.

    Science.gov (United States)

    Mero, Anna; Schiavon, Mariano; Veronese, Francesco M; Pasut, Gianfranco

    2011-08-25

    Modification of therapeutic proteins and peptides by polyethylene glycol (PEG) conjugation is a well-known approach to improve the pharmacological properties of drugs. Several chemical procedures of PEG coupling are already in use but an alternative method based on microbial transglutaminase (mTGase) was recently devised. The enzyme catalyzes the link of mPEG-NH(2) to glutamines (Gln) of a substrate protein. In this case the advantage resides in the fact that usually only few Gln(s) in a protein are substrate of mTGase. In order to further restrict the selectivity of the enzyme, we investigated a new approach leading to the formation of a single conjugate isomer as well as for those proteins containing two or more Gln(s) as mTGase substrates. It was found that the addition of co-solvents in the reaction mixture influenced both the secondary structure of the targeted protein and the mTGase activity. The enzymatic PEGylation under these conditions yielded only mono- and selectively modified conjugates. The method was investigated with salmon calcitonin (sCT) and human growth hormone (hGH). In the case of sCT we also demonstrated the importance of site-selective conjugation for the preservation of in vivo activity. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Technical report on material selection and processing guidelines for BWR [boiling water reactor] coolant pressure boundary piping: Final report

    International Nuclear Information System (INIS)

    Hazelton, W.S.; Koo, W.H.

    1988-01-01

    This report provides the technical bases for the NRC staff's revised recommended methods to control the intergranular stress corrosion cracking susceptibility of BWR piping. For piping that does not fully comply with the material selection, testing, and processing guideline combinations of this document, varying degrees of augmented inservice inspection are recommended. This revision also includes guidance and NRC staff recommendations (not requirements) regarding crack evaluation and weld overlay repair methods for long-term operation or for continuing interim operation of plants until a more permanent solution is implemented

  16. Internalization of appearance ideals mediates the relationship between appearance-related pressures from peers and emotional eating among adolescent boys and girls.

    Science.gov (United States)

    Thompson, Katherine A; Kelly, Nichole R; Schvey, Natasha A; Brady, Sheila M; Courville, Amber B; Tanofsky-Kraff, Marian; Yanovski, Susan Z; Yanovski, Jack A; Shomaker, Lauren B

    2017-01-01

    Appearance-related pressures have been associated with binge eating in previous studies. Yet, it is unclear if these pressures are associated with emotional eating or if specific sources of pressure are differentially associated with emotional eating. We studied the associations between multiple sources of appearance-related pressures, including pressure to be thin and pressure to increase muscularity, and emotional eating in 300 adolescents (M age =15.3, SD=1.4, 60% female). Controlling for age, race, puberty, body mass index (BMI) z-score, and sex, both pressure to be thin and pressure to be more muscular from same-sex peers were positively associated with emotional eating in response to feeling angry/frustrated and unsettled (pseating when depressed (peating in response to anger/frustration (pemotional eating were non-significant. Results considering sex as a moderator of the associations between appearance-related pressures and emotional eating were non-significant. Findings illustrate that both pressure to be thin and muscular from peers are related to more frequent emotional eating among both boys and girls, and these associations are explained through internalization of appearance-related ideals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Internalization of Appearance Ideals Mediates the Relationship between Appearance-Related Pressures from Peers and Emotional Eating among Adolescent Boys and Girls

    Science.gov (United States)

    Thompson, Katherine A.; Kelly, Nichole R.; Schvey, Natasha A.; Brady, Sheila M.; Courville, Amber B.; Tanofsky-Kraff, Marian; Yanovski, Susan Z.; Yanovski, Jack A.; Shomaker, Lauren B.

    2016-01-01

    Appearance-related pressures have been associated with binge eating in previous studies. Yet, it is unclear if these pressures are associated with emotional eating or if specific sources of pressure are differentially associated with emotional eating. We studied the associations between multiple sources of appearance-related pressures, including pressure to be thin and pressure to increase muscularity, and emotional eating in 300 adolescents (Mage = 15.3, SD = 1.4, 60% female). Controlling for age, race, puberty, body mass index (BMI) z-score, and sex, both pressure to be thin and pressure to be more muscular from same-sex peers were positively associated with emotional eating in response to feeling angry/frustrated and unsettled (pseating when depressed (peating in response to anger/frustration (pemotional eating were non-significant. Results considering sex as a moderator of the associations between appearance-related pressures and emotional eating were non-significant. Findings illustrate that both pressure to be thin and muscular from peers are related to more frequent emotional eating among both boys and girls, and these associations are explained through internalization of appearance-related ideals. PMID:28038437

  18. CRISPR-Mediated Drug-Target Validation Reveals Selective Pharmacological Inhibition of the RNA Helicase, eIF4A

    Directory of Open Access Journals (Sweden)

    Jennifer Chu

    2016-06-01

    Full Text Available Targeting translation initiation is an emerging anti-neoplastic strategy that capitalizes on de-regulated upstream MAPK and PI3K-mTOR signaling pathways in cancers. A key regulator of translation that controls ribosome recruitment flux is eukaryotic initiation factor (eIF 4F, a hetero-trimeric complex composed of the cap binding protein eIF4E, the scaffolding protein eIF4G, and the RNA helicase eIF4A. Small molecule inhibitors targeting eIF4F display promising anti-neoplastic activity in preclinical settings. Among these are some rocaglate family members that are well tolerated in vivo, deplete eIF4F of its eIF4A helicase subunit, have shown activity as single agents in several xenograft models, and can reverse acquired resistance to MAPK and PI3K-mTOR targeted therapies. Herein, we highlight the power of using genetic complementation approaches and CRISPR/Cas9-mediated editing for drug-target validation ex vivo and in vivo, linking the anti-tumor properties of rocaglates to eIF4A inhibition.

  19. Autonomous CaMKII Mediates Both LTP and LTD Using a Mechanism for Differential Substrate Site Selection

    Directory of Open Access Journals (Sweden)

    Steven J. Coultrap

    2014-02-01

    Full Text Available Traditionally, hippocampal long-term potentiation (LTP of synaptic strength requires Ca2+/calmodulin (CaM-dependent protein kinase II (CaMKII and other kinases, whereas long-term depression (LTD requires phosphatases. Here, we found that LTD also requires CaMKII and its phospho-T286-induced “autonomous” (Ca2+-independent activity. However, whereas LTP is known to induce phosphorylation of the AMPA-type glutamate receptor (AMPAR subunit GluA1 at S831, LTD instead induced CaMKII-mediated phosphorylation at S567, a site known to reduce synaptic GluA1 localization. GluA1 S831 phosphorylation by “autonomous” CaMKII was further stimulated by Ca2+/CaM, as expected for traditional substrates. By contrast, GluA1 S567 represents a distinct substrate class that is unaffected by such stimulation. This differential regulation caused GluA1 S831 to be favored by LTP-type stimuli (strong but brief, whereas GluA1 S567 was favored by LTD-type stimuli (weak but prolonged. Thus, requirement of autonomous CaMKII in opposing forms of plasticity involves distinct substrate classes that are differentially regulated to enable stimulus-dependent substrate-site preference.

  20. Beneficial effect of fluoxetine treatment aganist psychological stress is mediated by increasing BDNF expression in selected brain areas.

    Science.gov (United States)

    Li, Gongying; Jing, Ping; Liu, Zhidong; Li, Zhiruo; Ma, Hongxia; Tu, Wenzhen; Zhang, Wei; Zhuo, Chuanjun

    2017-09-19

    SSRI antidepressant fluoxetine is widely used to treat psychological stress related disorders, however the underlying working mechanisms is not fully understood, as SSRIs can rapidly increase the extracellular serotonin levels but it normally takes weeks to reveal their therapeutic effect in the stress-related psychological disorders. Our previous study demonstrated that purely psychological stress without any physic stimuli induces a biphasic change in the expression of brain-derived neurotrophic factor (BDNF), which immediately decrease and then gradually increase after the stress; and that the latter BDNF increase in response to the psychological stress involves the activation of serotonin system. To investigate the role of BDNF in the fluoxetine treatment for stress-related psychological disorders, we examined the mRNA and protein levels of BDNF in the brain of Sprague-Dawley (SD) rats, which were pretreated with fluoxetine at 10 mg/kg or vehicle solution for 14 days, over 24 hour after an acute psychological stress exposure. In situ hybridization and immunohistochemistry were performed to detect the expression of BDNF at different time points in various brain regions after the psychological stress. We found that fluoxetine treatment completely blocked the BDNF decrease induced by the psychological stress, and also enhanced the gradual increase in the expression of BDNF in most of the brain regions except VTA after the psychological stress. The results suggest that the enhancement in BDNF levels induced by chronic fluoxetine treatment mediates the therapeutic effect against psychological stress.

  1. Fault Diagnosis of Helical Coil Steam Generator Systems of an Integral Pressurized Water Reactor Using Optimal Sensor Selection

    Science.gov (United States)

    Li, Fan; Upadhyaya, Belle R.; Perillo, Sergio R. P.

    2012-04-01

    Fault diagnosis is an important area in nuclear power industry for effective and continuous operation of power plants. Fault diagnosis approaches depend critically on the sensors that measure important process variables. Allocation of these sensors determines the effectiveness of fault diagnostic methods. However, the emphasis of most approaches is primarily on the procedure to perform fault detection and isolation (FDI) given a set of sensors. Little attention has been given to actual allocation of the sensors for achieving efficient FDI performance. This paper presents a graph-based approach as a solution for optimization of sensor selection to ensure fault observability, as well as fault resolution to a maximum possible extent. Principal component analysis (PCA), a multivariate data-driven technique, is used to capture the relationships among the measurements and to characterize by a data hyper-plane. Fault directions for the different fault scenarios are obtained using singular value decomposition of the prediction errors, and fault isolation is then accomplished from new projections on these fault directions. Results of the helical coil steam generator (HCSG) system of the International Reactor Innovative and Secure (IRIS) nuclear reactor demonstrate the proposed FDI approach with optimized sensor selection, and its future application to large industrial systems.

  2. Selective pressure causes an RNA virus to trade reproductive fitness for increased structural and thermal stability of a viral enzyme.

    Directory of Open Access Journals (Sweden)

    Moshe Dessau

    Full Text Available The modulation of fitness by single mutational substitutions during environmental change is the most fundamental consequence of natural selection. The antagonistic tradeoffs of pleiotropic mutations that can be selected under changing environments therefore lie at the foundation of evolutionary biology. However, the molecular basis of fitness tradeoffs is rarely determined in terms of how these pleiotropic mutations affect protein structure. Here we use an interdisciplinary approach to study how antagonistic pleiotropy and protein function dictate a fitness tradeoff. We challenged populations of an RNA virus, bacteriophage Φ6, to evolve in a novel temperature environment where heat shock imposed extreme virus mortality. A single amino acid substitution in the viral lysin protein P5 (V207F favored improved stability, and hence survival of challenged viruses, despite a concomitant tradeoff that decreased viral reproduction. This mutation increased the thermostability of P5. Crystal structures of wild-type, mutant, and ligand-bound P5 reveal the molecular basis of this thermostabilization--the Phe207 side chain fills a hydrophobic cavity that is unoccupied in the wild-type--and identify P5 as a lytic transglycosylase. The mutation did not reduce the enzymatic activity of P5, suggesting that the reproduction tradeoff stems from other factors such as inefficient capsid assembly or disassembly. Our study demonstrates how combining experimental evolution, biochemistry, and structural biology can identify the mechanisms that drive the antagonistic pleiotropic phenotypes of an individual point mutation in the classic evolutionary tug-of-war between survival and reproduction.

  3. Pressure dependence of conductivity

    International Nuclear Information System (INIS)

    Bracewell, B.L.; Hochheimer, H.D.

    1993-01-01

    The overall objectives of this work were to attempt the following: (1) Measure the pressure dependence of the electrical conductivity of several quasi-one-dimensional, charge-density-wave solids, including measurements along various crystal directions. (2) Measure photocurrents in selected MX solids at ambient and elevated pressures. (3) Measure the resonance Raman spectra for selected MX solids as a function of pressure

  4. Influence of FGR complexity modelling on the practical results in gas pressure calculation of selected fuel elements from Dukovany NPP

    International Nuclear Information System (INIS)

    Lahodova, M.

    2001-01-01

    A modernization fuel system and advanced fuel for operation up to the high burnup are used in present time in Dukovany NPP. Reloading of the cores are evaluated using computer codes for thermomechanical behavior of the most loaded fuel rods. The paper presents results of parametric calculations performed by the NRI Rez integral code PIN, version 2000 (PIN2k) to assess influence of fission gas release modelling complexity on achieved results. The representative Dukovany NPP fuel rod irradiation history data are used and two cases of fuel parameter variables (soft and hard) are chosen for the comparison. Involved FGR models where the GASREL diffusion model developed in the NRI Rez plc and standard Weisman model that is recommended in the previous version of the PIN integral code. FGR calculation by PIN2k with GASREL model represents more realistic results than standard Weisman's model. Results for linear power, fuel centre temperature, FGR and gas pressure versus burnup are given for two fuel rods

  5. Well-Known Mediators of Selective Oxidation with Unknown Electronic Structure: Metal-Free Generation and EPR Study of Imide-N-oxyl Radicals.

    Science.gov (United States)

    Krylov, Igor B; Kompanets, Mykhailo O; Novikova, Katerina V; Opeida, Iosip O; Kushch, Olga V; Shelimov, Boris N; Nikishin, Gennady I; Levitsky, Dmitri O; Terent'ev, Alexander O

    2016-01-14

    Nitroxyl radicals are widely used in chemistry, materials sciences, and biology. Imide-N-oxyl radicals are subclass of unique nitroxyl radicals that proved to be useful catalysts and mediators of selective oxidation and CH-functionalization. An efficient metal-free method was developed for the generation of imide-N-oxyl radicals from N-hydroxyimides at room temperature by the reaction with (diacetoxyiodo)benzene. The method allows for the production of high concentrations of free radicals and provides high resolution of their EPR spectra exhibiting the superhyperfine structure from benzene ring protons distant from the radical center. An analysis of the spectra shows that, regardless of the electronic effects of the substituents in the benzene ring, the superhyperfine coupling constant of an unpaired electron with the distant protons at positions 4 and 5 of the aromatic system is substantially greater than that with the protons at positions 3 and 6 that are closer to the N-oxyl radical center. This is indicative of an unusual character of the spin density distribution of the unpaired electron in substituted phthalimide-N-oxyl radicals. Understanding of the nature of the electron density distribution in imide-N-oxyl radicals may be useful for the development of commercial mediators of oxidation based on N-hydroxyimides.

  6. Novel metal-ion-mediated, complex-imprinted solid-phase microextraction fiber for the selective recognition of thiabendazole in citrus and soil samples.

    Science.gov (United States)

    Lian, Haixian; Hu, Yuling; Li, Gongke

    2014-01-01

    A novel metal-ion-mediated complex-imprinted-polymer-coated solid-phase microextraction (SPME) fiber used to specifically recognize thiabendazole (TBZ) in citrus and soil samples was developed. The complex-imprinted polymer was introduced as a novel SPME coating using a "complex template" constructed with Cu(II) ions and TBZ. The recognition and enrichment properties of the coating in water were significantly improved based on the metal ion coordination interaction rather than relying on hydrogen bonding interactions that are commonly applied for the molecularly imprinting technique. Several parameters controlling the extraction performance of the complex-imprinted-polymer-coated fiber were investigated including extraction solvent, pH value, extraction time, metal ion species, etc. Furthermore, SPME coupled with HPLC was developed for detection of TBZ, and the methods resulted in good linearity in the range of 10.0-150.0 ng/mL with a detection limit of 2.4 ng/mL. The proposed method was applied to the analysis of TBZ in spiked soil, orange, and lemon with recoveries of 80.0-86.9% and RSDs of 2.0-8.1%. This research provides an example to prepare a desirable water-compatible and specifically selective SPME coating to extract target molecules from aqueous samples by introducing metal ions as the mediator. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Gene-environment correlation in the development of adolescent substance abuse: selection effects of child personality and mediation via contextual risk factors.

    Science.gov (United States)

    Hicks, Brian M; Johnson, Wendy; Durbin, C Emily; Blonigen, Daniel M; Iacono, William G; McGue, Matt

    2013-02-01

    We used a longitudinal twin design to examine selection effects of personality traits at age 11 on high-risk environmental contexts at age 14 and the extent to which these contexts mediated risk for substance abuse at age 17. Socialization at age 11 (willingness to follow rules and endorse conventional values) predicted exposure to contextual risk at age 14. Contextual risk partially mediated the effect of socialization on substance abuse, though socialization also had a direct effect. In contrast, boldness at age 11 (social engagement and assurance, thrill seeking, and stress resilience) also predicted substance abuse directly but was unrelated to contextual risk. There was substantial overlap in the genetic and shared environmental influences on socialization and contextual risk, and genetic risk in socialization contributed to substance abuse indirectly via increased exposure to contextual risk. This suggests that active gene-environment correlations related to individual differences in socialization contributed to an early, high-risk developmental trajectory for adolescent substance abuse. In contrast, boldness appeared to index an independent and direct genetic risk factor for adolescent substance abuse.

  8. Selective inhibition of the gliadin-specific, cell-mediated immune response by transamidation with microbial transglutaminase.

    Science.gov (United States)

    Lombardi, Emanuela; Bergamo, Paolo; Maurano, Francesco; Bozzella, Giuseppina; Luongo, Diomira; Mazzarella, Giuseppe; Rotondi Aufiero, Vera; Iaquinto, Gaetano; Rossi, Mauro

    2013-04-01

    CD is an immune-mediated enteropathy caused by the ingestion of wheat gluten. The modification of gluten by intestinal tTGase plays a crucial role in CD pathogenesis. In this study, we observed that extensive transamidation of wheat flour with K-C2H5 by mTGase yielded spf and K-gliadins fractions. By Western blot, we found that these modifications were associated with strongly reduced immune cross-reactivity. With the use of DQ8 tg mice as a model of gluten sensitivity, we observed a dramatic reduction in IFNγ production in gliadin-specific spleen cells challenged with spf and K-gliadins in vitro (n=12; median values: 813 vs. 29 and 99; control vs. spf and K-gliadins, P=0.012 for spf, and P=0.003 for K-gliadins). For spf, we also observed an increase in the IL-10/IFNγ protein ratio (n=12; median values: 0.3 vs. 4.7; control vs. spf, P=0.005). In intestinal biopsies from CD patients challenged in vitro with gliadins (n=10), we demonstrated further that K-gliadins dramatically reduced the levels of antigen-specific IFNγ mRNA in all specimens responsive to native gliadins (four of 10; Pactivities using the enterocytic Caco-2 cell line. We found that neither activities were modified by flour transamidation. Our results indicate that K-C2H5 cross-linking via mTGase specifically affects gliadin immunogenicity, reversing the inducible inflammatory response in models of gluten sensitivity without affecting other aspects of the biological activity of gliadins.

  9. Selection system and co-cultivation medium are important determinants of Agrobacterium-mediated transformation of sugarcane.

    Science.gov (United States)

    Joyce, Priya; Kuwahata, Melissa; Turner, Nicole; Lakshmanan, Prakash

    2010-02-01

    A reproducible method for transformation of sugarcane using various strains of Agrobacterium tumefaciens (A. tumefaciens) (AGL0, AGL1, EHA105 and LBA4404) has been developed. The selection system and co-cultivation medium were the most important factors determining the success of transformation and transgenic plant regeneration. Plant regeneration at a frequency of 0.8-4.8% occurred only when callus was transformed with A. tumefaciens carrying a newly constructed superbinary plasmid containing neomycin phosphotransferase (nptII) and beta-glucuronidase (gusA) genes, both driven by the maize ubiquitin (ubi-1) promoter. Regeneration was successful in plants carrying the nptII gene but not the hygromycin phosphotransferase (hph) gene. NptII gene selection was imposed at a concentration of 150 mg/l paromomycin sulphate and applied either immediately or 4 days after the co-cultivation period. Co-cultivation on Murashige and Skoog (MS)-based medium for a period of 4 days produced the highest number of transgenic plants. Over 200 independent transgenic lines were created using this protocol. Regenerated plants appeared phenotypically normal and contained both gusA and nptII genes. Southern blot analysis revealed 1-3 transgene insertion events that were randomly integrated in the majority of the plants produced.

  10. Time and space resolved deep metagenomics to investigate selection pressures on low abundant species in complex environments

    DEFF Research Database (Denmark)

    Albertsen, Mads; Saunders, Aaron Marc; Nielsen, Kåre Lehmann

    Metagenomics offers great potential for investigation of species and strain diversification over time. Recent progress in sequencing technologies have made it possible to investigate species diversification and niche adaptation in low abundant populations (... Biological Phosphorus Removal (EBPR) wastewater treatment plants using qFISH and 16S sequencing and identified a surprisingly stable core community. This makes EBPR a prime target for metagenomic investigations of species diversification over time and between plants. The aim of the project was to investigate...... and between EBPR plants we sequenced a total of 10 samples from 3 different plants over a 3 year period at a depth of 25 Gb each. In addition, one time point was selected for deep sequencing, generating 200 Gb of sequence divided between replicates. Quantitative FISH analysis using >30 oligonucleotide probes...

  11. The interleukin-15 system suppresses T cell-mediated autoimmunity by regulating negative selection and nT(H)17 cell homeostasis in the thymus.

    Science.gov (United States)

    Hou, Mau-Sheng; Huang, Shih-Ting; Tsai, Ming-Han; Yen, Ching-Cheng; Lai, Yein-Gei; Liou, Yae-Huei; Lin, Chih-Kung; Liao, Nan-Shih

    2015-01-01

    The interleukin-15 (IL-15) system is important for regulating both innate and adaptive immune responses, however, its role in autoimmune disease remained unclear. Here we found that Il15(-/-) and Il15ra(-/-) mice spontaneously developed late-onset autoimmune phenotypes. CD4(+) T cells of the knockout mice showed elevated autoreactivity as demonstrated by the induction of lymphocyte infiltration in the lacrimal and salivary glands when transferred into nude mice. The antigen-presenting cells in the thymic medullary regions expressed IL-15 and IL-15Rα, whose deficiency resulted in insufficient negative selection and elevated number of natural IL-17A-producing CD4(+) thymocytes. These findings reveal previously unknown functions of the IL-15 system in thymocyte development, and thus a new layer of regulation in T cell-mediated autoimmunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Accounting for Selectivity Bias and Correlation Across the Sequence From Elevated Blood Pressure to Hypertension Diagnosis and Treatment.

    Science.gov (United States)

    Gordon-Larsen, Penny; Attard, Samantha M; Howard, Annie Green; Popkin, Barry M; Zhang, Bing; Du, Shufa; Guilkey, David K

    2017-12-08

    It is unknown whether efforts to reduce hypertension burden in countries with very high prevalence, would be more effective if directed at hypertension diagnosis vs. treatment. Most analyses do not address bias and correlation across the sequence from elevated blood pressure (BP) to hypertension diagnosis and treatment, leading to potentially misleading findings. Using data spanning 18 years of the China Health and Nutrition Survey (n = 18,926; ages 18-75 years), we used an innovative 3-step, integrated system of equations to predict the sequence from: (i) elevated BP (systolic/diastolic BP ≥ 140/90 mm Hg) to (ii) diagnosed hypertension conditional on elevated BP, and to (iii) treatment (medication use) conditional on diagnosis, accounting for measured and unmeasured individual- and community-level confounders at each of the 3 steps. We compared results to separate traditional logistic regression models without control for unmeasured confounding. Using our 3-step model, elevated BP increased from 12.6% and 8.5% (1991) to 36.8% and 29% (2009) in men and women, respectively, but diagnosis remained under 50%. We found widening disparities in hypertension diagnosis (higher hypertension at lower vs. higher education (difference of 2% in 1991 that widened to 5% in 2009)) and narrowing disparities in education (difference of 6% in 1991 to 4% in 2009) and insurance status (difference of 7% in 1991 to 2% in 2009) for treatment. Our 3-step model improved model fit over traditionally used models. Our findings highlight serious barriers to hypertension diagnosis in Chinese adults, particularly among men and individuals of low attained education. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  13. (-)1-(Benzofuran-2-yl)-2-propylaminopentane, [(-)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain.

    Science.gov (United States)

    Knoll, J; Yoneda, F; Knoll, B; Ohde, H; Miklya, I

    1999-12-01

    1. The brain constituents beta-phenylethylamine (PEA) and tryptamine enhance the impulse propagation mediated transmitter release (exocytosis) from the catecholaminergic and serotoninergic neurons in the brain ('catecholaminergic/serotoninergic activity enhancer, CAE/SAE, effect'). (-)Deprenyl (Selegiline) and (-)1-phenyl-2-propylaminopentane [(-)PPAP] are amphetamine derived CAE substances devoid of the catecholamine releasing property. 2. By changing the aromatic ring in PPAP we developed highly potent and selective CAE/SAE substances, structurally unrelated to the amphetamines. Out of 65 newly synthetized compounds, a tryptamine derived structure, (-)1-(benzofuran-2-yl)-2-propylaminopentane [(-)BPAP] was selected as a potential follower of (-)deprenyl in the clinic and as a reference compound for further analysis of the CAE/SAE mechanism in the mammalian brain. 3. (-)BPAP significantly enhanced in 0.18 micromol 1(-1) concentration the impulse propagation mediated release of [(3)H]-noradrenaline and [(3)H]-dopamine and in 36 nmol 1(-1) concentration the release of [(3)H]-serotonin from the isolated brain stem of rats. The amount of catecholamines and serotonin released from isolated discrete rat brain regions (dopamine from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from the locus coeruleus and serotonin from the raphe) enhanced significantly in the presence of 10(-12) - 10(-14) M (-)BPAP. BPAP protected cultured hippocampal neurons from the neurotoxic effect of beta-amyloid in 10(-14) M concentration. In rats (-)BPAP significantly enhanced the activity of the catecholaminergic and serotoninergic neurons in the brain 30 min after acute injection of 0.1 microg kg(-1) s.c. In the shuttle box, (-)BPAP in rats was about 130 times more potent than (-)deprenyl in antagonizing tetrabenazine induced inhibition of performance.

  14. (−)1-(Benzofuran-2-yl)-2-propylaminopentane, [(−)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain

    Science.gov (United States)

    Knoll, Joseph; Yoneda, Fumio; Knoll, Berta; Ohde, Hironori; Miklya, Ildikó

    1999-01-01

    The brain constituents β-phenylethylamine (PEA) and tryptamine enhance the impulse propagation mediated transmitter release (exocytosis) from the catecholaminergic and serotoninergic neurons in the brain (‘catecholaminergic/serotoninergic activity enhancer, CAE/SAE, effect'). (−)Deprenyl (Selegiline) and (−)1-phenyl-2-propylaminopentane [(−)PPAP] are amphetamine derived CAE substances devoid of the catecholamine releasing property.By changing the aromatic ring in PPAP we developed highly potent and selective CAE/SAE substances, structurally unrelated to the amphetamines. Out of 65 newly synthetized compounds, a tryptamine derived structure, (−)1-(benzofuran-2-yl)-2-propylaminopentane [(−)BPAP] was selected as a potential follower of (−)deprenyl in the clinic and as a reference compound for further analysis of the CAE/SAE mechanism in the mammalian brain.(−)BPAP significantly enhanced in 0.18 μmol 1−1 concentration the impulse propagation mediated release of [3H]-noradrenaline and [3H]-dopamine and in 36 nmol 1−1 concentration the release of [3H]-serotonin from the isolated brain stem of rats. The amount of catecholamines and serotonin released from isolated discrete rat brain regions (dopamine from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from the locus coeruleus and serotonin from the raphe) enhanced significantly in the presence of 10−12–10−14 M (−)BPAP. BPAP protected cultured hippocampal neurons from the neurotoxic effect of β-amyloid in 10−14 M concentration. In rats (−)BPAP significantly enhanced the activity of the catecholaminergic and serotoninergic neurons in the brain 30 min after acute injection of 0.1 μg kg−1 s.c. In the shuttle box, (−)BPAP in rats was about 130 times more potent than (−)deprenyl in antagonizing tetrabenazine induced inhibition of performance. PMID:10588928

  15. Dynamic treatment selection and modification for personalised blood pressure therapy using a Markov decision process model: a cost-effectiveness analysis.

    Science.gov (United States)

    Choi, Sung Eun; Brandeau, Margaret L; Basu, Sanjay

    2017-11-15

    Personalised medicine seeks to select and modify treatments based on individual patient characteristics and preferences. We sought to develop an automated strategy to select and modify blood pressure treatments, incorporating the likelihood that patients with different characteristics would benefit from different types of medications and dosages and the potential severity and impact of different side effects among patients with different characteristics. We developed a Markov decision process (MDP) model to incorporate meta-analytic data and estimate the optimal treatment for maximising discounted lifetime quality-adjusted life-years (QALYs) based on individual patient characteristics, incorporating medication adjustment choices when a patient incurs side effects. We compared the MDP to current US blood pressure treatment guidelines (the Eighth Joint National Committee, JNC8) and a variant of current guidelines that incorporates results of a major recent trial of intensive treatment (Intensive JNC8). We used a microsimulation model of patient demographics, cardiovascular disease risk factors and side effect probabilities, sampling from the National Health and Nutrition Examination Survey (2003-2014), to compare the expected population outcomes from adopting the MDP versus guideline-based strategies. Costs and QALYs for the MDP-based treatment (MDPT), JNC8 and Intensive JNC8 strategies. Compared with the JNC8 guideline, the MDPT strategy would be cost-saving from a societal perspective with discounted savings of US$1187 per capita (95% CI 1178 to 1209) and an estimated discounted gain of 0.06 QALYs per capita (95% CI 0.04 to 0.08) among the US adult population. QALY gains would largely accrue from reductions in severe side effects associated with higher treatment doses later in life. The Intensive JNC8 strategy was dominated by the MDPT strategy. An MDP-based approach can aid decision-making by incorporating meta-analytic evidence to personalise blood pressure

  16. The highly selective oxidation of cyclohexane to cyclohexanone and cyclohexanol over VAlPO4 berlinite by oxygen under atmospheric pressure.

    Science.gov (United States)

    Hong, Yun; Sun, Dalei; Fang, Yanxiong

    2018-04-04

    The oxidation of cyclohexane under mild conditions occupies an important position in the chemical industry. A few soluble transition metals were widely used as homogeneous catalysts in the industrial oxidation of cyclohexane. Because heterogeneous catalysts are more manageable than homogeneous catalysts as regards separation and recycling, in our study, we hydrothermally synthesized and used pure berlinite (AlPO 4 ) and vanadium-incorporated berlinite (VAlPO 4 ) as heterogeneous catalysts in the selective oxidation of cyclohexane with molecular oxygen under atmospheric pressure. The catalysts were characterized by means of by XRD, FT-IR, XPS and SEM. Various influencing factors, such as the kind of solvents, reaction temperature, and reaction time were investigated systematically. The XRD characterization identified a berlinite structure associated with both the AlPO 4 and VAlPO 4 catalysts. The FT-IR result confirmed the incorporation of vanadium into the berlinite framework for VAlPO 4 . The XPS measurement revealed that the oxygen ions in the VAlPO 4 structure possessed a higher binding energy than those in V 2 O 5 , and as a result, the lattice oxygen was existed on the surface of the VAlPO 4 catalyst. It was found that VAlPO 4 catalyzed the selective oxidation of cyclohexane with molecular oxygen under atmospheric pressure, while no activity was detected on using AlPO 4 . Under optimum reaction conditions (i.e. a 100 mL cyclohexane, 0.1 MPa O 2 , 353 K, 4 h, 5 mg VAlPO 4 and 20 mL acetic acid solvent), a selectivity of KA oil (both cyclohexanol and cyclohexanone) up to 97.2% (with almost 6.8% conversion of cyclohexane) was obtained. Based on these results, a possible mechanism for the selective oxidation of cyclohexane over VAlPO 4 was also proposed. As a heterogeneous catalyst VAlPO 4 berlinite is both high active and strong stable for the selective oxidation of cyclohexane with molecular oxygen. We propose that KA oil is formed via a catalytic cycle

  17. Effect of atmospheric-pressure plasma treatment on the adhesion properties of a thin adhesive layer in a selective transfer process

    Science.gov (United States)

    Yoon, Min-Ah; Kim, Chan; Hur, Min; Kang, Woo Seok; Kim, Jaegu; Kim, Jae-Hyun; Lee, Hak-Joo; Kim, Kwang-Seop

    2018-01-01

    The adhesion between a stamp and thin film devices is crucial for their transfer on a flexible substrate. In this paper, a thin adhesive silicone layer on the stamp was treated by atmospheric pressure plasma to locally control the adhesion strength for the selective transfer. The adhesion strength of the silicone layer was significantly reduced after the plasma treatment, while its surface energy was increased. To understand the inconsistency between the adhesion strength and surface energy changes, the surface properties of the silicone layer were characterized using nanoindentation and X-ray photoelectron spectroscopy. These techniques revealed that a thin, hard, silica-like layer had formed on the surface from plasma-enhanced oxidation. This layer played an important role in decreasing the contact area and increasing the interfacial slippage, resulting in decreased adhesion. As a practical application, the transfer process was demonstrated on GaN LEDs that had been previously delaminated by a laser lift-off (LLO) process. Although the LEDs were not transferred onto the treated adhesive layer due to the reduced adhesion, the untreated adhesive layer could readily pick up the LEDs. It is expected that this simple method of controlling the adhesion of a stamp with a thin adhesive layer would enable a continuous, selective and large-scale roll-to-roll selective transfer process and thereby advance the development of flexible, stretchable and wearable electronics.

  18. Beta-adrenergic receptor 1 selective antagonism inhibits norepinephrine-mediated TNF-alpha downregulation in experimental liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Pedro Zapater

    Full Text Available BACKGROUND: Bacterial translocation is a frequent event in cirrhosis leading to an increased inflammatory response. Splanchnic adrenergic system hyperactivation has been related with increased bacterial translocation. We aim at evaluating the interacting mechanism between hepatic norepinephrine and inflammation during liver damage in the presence of bacterial-DNA. ANIMALS AND METHODS: Forty-six mice were included in a 16-week protocol of CCl(4-induced cirrhosis. Laparotomies were performed at weeks 6, 10, 13 and 16. A second set of forty mice injected with a single intraperitoneal dose of CCl(4 was treated with saline, 6-hydroxidopamine, Nebivolol or Butoxamine. After 5 days, mice received E. coli-DNA intraperitoneally. Laparotomies were performed 24 hours later. Liver bacterial-DNA, norepinephrine, TNF-alpha, IL-6 and beta-adrenergic receptor levels were measured. RESULTS: Bacterial-DNA translocation was more frequent in CCl(4-treated animals compared with controls, and increased as fibrosis progressed. Liver norepinephrine and pro-inflammatory cytokines were significantly higher in mice with vs without bacterial-DNA (319.7 ± 120.6 vs 120.7 ± 68.6 pg/g for norepinephrine, 38.4 ± 6.1 vs 29.7 ± 4.2 pg/g for TNF-alpha, 41.8 ± 7.4 vs 28.7 ± 4.3 pg/g for IL-6. Only beta-adrenergic receptor-1 was significantly increased in treated vs control animals (34.6 ± 7.3 vs 12.5 ± 5.3, p=0.01 and correlated with TNF-alpha, IL-6 and norepinephrine hepatic levels in animals with bacterial-DNA. In the second set of mice, cytokine levels were increased in 6-hydroxidopamine and Nebivolol (beta-adrenergic receptor-1 antagonist treated mice compared with saline. Butoxamine (beta-adrenergic receptor-2 antagonist didn't inhibit liver norepinephrine modulation of pro-inflammatory cytokines. CONCLUSIONS: Beta-adrenergic receptor-1 mediates liver norepinephrine modulation of the pro-inflammatory response in CCl(4-treated mice with bacterial-DNA.

  19. Silver ion mediated shape control of platinum nanoparticles: Removal of silver by selective etching leads to increased catalytic activity

    Energy Technology Data Exchange (ETDEWEB)

    Grass, Michael E.; Yue, Yao; Habas, Susan E.; Rioux, Robert M.; Teall, Chelsea I.; Somorjai, G.A.

    2008-01-09

    A procedure has been developed for the selective etching of Ag from Pt nanoparticles of well-defined shape, resulting in the formation of elementally-pure Pt cubes, cuboctahedra, or octahedra, with a largest vertex-to-vertex distance of {approx}9.5 nm from Ag-modified Pt nanoparticles. A nitric acid etching process was applied Pt nanoparticles supported on mesoporous silica, as well as nanoparticles dispersed in aqueous solution. The characterization of the silica-supported particles by XRD, TEM, and N{sub 2} adsorption measurements demonstrated that the structure of the nanoparticles and the mesoporous support remained conserved during etching in concentrated nitric acid. Both elemental analysis and ethylene hydrogenation indicated etching of Ag is only effective when [HNO{sub 3}] {ge} 7 M; below this concentration, the removal of Ag is only {approx}10%. Ethylene hydrogenation activity increased by four orders of magnitude after the etching of Pt octahedra that contained the highest fraction of silver. High-resolution transmission electron microscopy of the unsupported particles after etching demonstrated that etching does not alter the surface structure of the Pt nanoparticles. High [HNO{sub 3}] led to the decomposition of the capping agent, polyvinylpyrollidone (PVP); infrared spectroscopy confirmed that many decomposition products were present on the surface during etching, including carbon monoxide.

  20. Using mixed methods to select optimal mode of administration for a patient-reported outcome instrument for people with pressure ulcers.

    Science.gov (United States)

    Rutherford, Claudia; Nixon, Jane; Brown, Julia M; Lamping, Donna L; Cano, Stefan J

    2014-02-12

    When developing new measuring instruments or deciding upon one for research, consideration of the 'best' method of administration for the target population should be made. Current evidence is inconsistent in differentiating superiority of any one method in terms of quantity and quality of response. We trialed a novel mixed methods approach in early scale development to determine the best administration method for a new patient-reported outcome instrument for people with pressure ulcers (the PU-QOL). Cognitive interviews were undertaken with 35 people with pressure ulcers to determine appropriateness of a self-completed version of the PU-QOL instrument. Quantitative analysis, including Rasch analysis, was carried out on PU-QOL data from 70 patients with pressure ulcers, randomised to self-completed or interview-administered groups, to examine data quality and differential item functioning (DIF). Cognitive interviews identified issues with PU-QOL self-completion. Quantitative analysis supported these findings with a large proportion of self-completed PU-QOLs returned with missing data. DIF analysis indicated administration methods did not impact the way patients from community care settings responded, supporting the equivalence of both administration versions. Obtaining the best possible health outcomes data requires use of appropriate methods to ensure high quality data with minimal bias. Mixed methods, with the inclusion of Rasch, provided valuable evidence to support selection of the 'best' administration method for people with PUs during early PRO instrument development. We consider our approach to be generic and widely applicable to other elderly or chronically ill populations or suitable for use in limited samples where recruitment to large field tests is often difficult.

  1. Water absorption lines, 931-961 nm - Selected intensities, N2-collision-broadening coefficients, self-broadening coefficients, and pressure shifts in air

    Science.gov (United States)

    Giver, L. P.; Gentry, B.; Schwemmer, G.; Wilkerson, T. D.

    1982-01-01

    Intensities were measured for 97 lines of H2O vapor between 932 and 961 nm. The lines were selected for their potential usefulness for remote laser measurements of H2O vapor in the earth's atmosphere. The spectra were obtained with several different H2O vapor abundances and N2 broadening gas pressures; the spectral resolution was 0.046/cm FWHM. Measured H2O line intensities range from 7 x 10 to the -25th to 7 x 10 to the -22nd/cm per (molecules/sq cm). H2O self-broadening coefficients were measured for 13 of these strongest lines; the mean value was 0.5/cm per atm. N2-collision-broadening coefficients were measured for 73 lines, and the average was 0.11 cm per atm HWHM. Pressure shifts in air were determined for a sample of six lines between 948 and 950 nm; these lines shift to lower frequency by an amount comparable to 0.1 of the collision-broadened widths measured in air or N2. The measured intensities of many lines of 300-000 band are much larger than expected from prior computations, in some cases by over an order of magnitude. Coriolis interactions with the stronger 201-000 band appear to be the primary cause of the enhancement of these line intensities.

  2. Dihydrofolate-Reductase Mutations in Plasmodium knowlesi Appear Unrelated to Selective Drug Pressure from Putative Human-To-Human Transmission in Sabah, Malaysia.

    Directory of Open Access Journals (Sweden)

    Matthew J Grigg

    Full Text Available Malaria caused by zoonotic Plasmodium knowlesi is an emerging threat in Eastern Malaysia. Despite demonstrated vector competency, it is unknown whether human-to-human (H-H transmission is occurring naturally. We sought evidence of drug selection pressure from the antimalarial sulfadoxine-pyrimethamine (SP as a potential marker of H-H transmission.The P. knowlesi dihdyrofolate-reductase (pkdhfr gene was sequenced from 449 P. knowlesi malaria cases from Sabah (Malaysian Borneo and genotypes evaluated for association with clinical and epidemiological factors. Homology modelling using the pvdhfr template was used to assess the effect of pkdhfr mutations on the pyrimethamine binding pocket.Fourteen non-synonymous mutations were detected, with the most common being at codon T91P (10.2% and R34L (10.0%, resulting in 21 different genotypes, including the wild-type, 14 single mutants, and six double mutants. One third of the P. knowlesi infections were with pkdhfr mutants; 145 (32% patients had single mutants and 14 (3% had double-mutants. In contrast, among the 47 P. falciparum isolates sequenced, three pfdhfr genotypes were found, with the double mutant 108N+59R being fixed and the triple mutants 108N+59R+51I and 108N+59R+164L occurring with frequencies of 4% and 8%, respectively. Two non-random spatio-temporal clusters were identified with pkdhfr genotypes. There was no association between pkdhfr mutations and hyperparasitaemia or malaria severity, both hypothesized to be indicators of H-H transmission. The orthologous loci associated with resistance in P. falciparum were not mutated in pkdhfr. Subsequent homology modelling of pkdhfr revealed gene loci 13, 53, 120, and 173 as being critical for pyrimethamine binding, however, there were no mutations at these sites among the 449 P. knowlesi isolates.Although moderate diversity was observed in pkdhfr in Sabah, there was no evidence this reflected selective antifolate drug pressure in humans.

  3. Dihydrofolate-Reductase Mutations in Plasmodium knowlesi Appear Unrelated to Selective Drug Pressure from Putative Human-To-Human Transmission in Sabah, Malaysia.

    Science.gov (United States)

    Grigg, Matthew J; Barber, Bridget E; Marfurt, Jutta; Imwong, Mallika; William, Timothy; Bird, Elspeth; Piera, Kim A; Aziz, Ammar; Boonyuen, Usa; Drakeley, Christopher J; Cox, Jonathan; White, Nicholas J; Cheng, Qin; Yeo, Tsin W; Auburn, Sarah; Anstey, Nicholas M

    2016-01-01

    Malaria caused by zoonotic Plasmodium knowlesi is an emerging threat in Eastern Malaysia. Despite demonstrated vector competency, it is unknown whether human-to-human (H-H) transmission is occurring naturally. We sought evidence of drug selection pressure from the antimalarial sulfadoxine-pyrimethamine (SP) as a potential marker of H-H transmission. The P. knowlesi dihdyrofolate-reductase (pkdhfr) gene was sequenced from 449 P. knowlesi malaria cases from Sabah (Malaysian Borneo) and genotypes evaluated for association with clinical and epidemiological factors. Homology modelling using the pvdhfr template was used to assess the effect of pkdhfr mutations on the pyrimethamine binding pocket. Fourteen non-synonymous mutations were detected, with the most common being at codon T91P (10.2%) and R34L (10.0%), resulting in 21 different genotypes, including the wild-type, 14 single mutants, and six double mutants. One third of the P. knowlesi infections were with pkdhfr mutants; 145 (32%) patients had single mutants and 14 (3%) had double-mutants. In contrast, among the 47 P. falciparum isolates sequenced, three pfdhfr genotypes were found, with the double mutant 108N+59R being fixed and the triple mutants 108N+59R+51I and 108N+59R+164L occurring with frequencies of 4% and 8%, respectively. Two non-random spatio-temporal clusters were identified with pkdhfr genotypes. There was no association between pkdhfr mutations and hyperparasitaemia or malaria severity, both hypothesized to be indicators of H-H transmission. The orthologous loci associated with resistance in P. falciparum were not mutated in pkdhfr. Subsequent homology modelling of pkdhfr revealed gene loci 13, 53, 120, and 173 as being critical for pyrimethamine binding, however, there were no mutations at these sites among the 449 P. knowlesi isolates. Although moderate diversity was observed in pkdhfr in Sabah, there was no evidence this reflected selective antifolate drug pressure in humans.

  4. Selective pressure for allelic diversity in SeM of Streptococcus equi does not affect immunoreactive proteins SzPSe or Se18.9.

    Science.gov (United States)

    Ijaz, Muhammad; Velineni, Sridhar; Timoney, John F

    2011-07-01

    Streptococcus equi, a clone or biovar of an ancestral Streptococcus zooepidemicus of Lancefield group C causes equine strangles, a highly contagious tonsillitis and lymphadenitis of the head and neck. At least 74 alleles based on N-terminal amino acid sequence of the anti-phagocytic SeM have been observed among isolates of S. equi from N. America, Europe and Japan. A d(N)/d(S) ratio of 5.93 for the 5' region of sem is indicative of positive selective pressure. The aim of this study was to determine whether variations in SeM were accompanied by variations in the surface exposed SzPSe and secreted Se18.9, both of which bind to equine tonsillar epithelium and, along with SeM, elicit strong nasopharyngeal IgA responses during convalescence. Sequences of genes for these proteins from 25 S. equi expressing 19 different SeM alleles isolated over 40 years in different countries were compared. No variation was observed in szpse, except for an Australian isolate with a deletion of a single repeat in the 3' end of the gene. Interestingly, only two SNP loci were detected in se18.9 compared to 93 and 55 in sem and szpse, respectively. The high frequency of nucleotide substitutions in szpse may be related to its mosaic structure since this gene in S. zooepidemicus exists in a variety of combinations of sequence segments and has a central hypervariable region that includes exogenous DNA sequence based on an atypical G-C percentage. In summary, the results of this study document very different responses of streptococcal genes for 3 immunoreactive proteins to selection pressure of the nasopharyngeal mucosal immune response. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Water-soluble chitosan derivatives and pH-responsive hydrogels by selective C-6 oxidation mediated by TEMPO-laccase redox system.

    Science.gov (United States)

    Botelho da Silva, Suse; Krolicka, Malgorzata; van den Broek, Lambertus A M; Frissen, August E; Boeriu, Carmen Gabriela

    2018-04-15

    Chitosan is a polysaccharide with recognized antioxidant, antimicrobial and wound healing activities. However, this polymer is soluble only in dilute acidic solutions, which restricts much of its applications. A usual strategy for improving the functionality of polysaccharides is the selective oxidation mediated by 2,2,6,6-tetra-methyl-1-piperidinidyloxy (TEMPO) using laccase as a co-oxidant. In this work, the TEMPO-laccase redox system was used for the first time to selectively oxidize chitosan in order to produce tailored derivatives. The reaction was performed at pH 4.5 under continuous air supply and the oxidized products were characterized structurally and functionally. The TEMPO-laccase oxidation successfully added aldehyde and carboxylate groups to chitosan structure resulting in derivatives with oxidation between 4 and 7%. These derivatives showed increased solubility and decreased viscosity in solution. If chitosan is dissolved in diluted hydrochloric acid prior to TEMPO-laccase oxidation, a crosslinked chitosan derivative was produced, which was able to form a pH-responsive hydrogel. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Annatto constituent cis-bixin has selective antimyeloma effects mediated by oxidative stress and associated with inhibition of thioredoxin and thioredoxin reductase.

    Science.gov (United States)

    Tibodeau, Jennifer D; Isham, Crescent R; Bible, Keith C

    2010-10-01

    In pursuit of the anticancer effects of seeds of the rain forest plant Bixa orellana (annatto), we found that its constituent cis-bixin induced cytotoxicity in a wide variety of tumor cell lines (IC(50) values from 10 to 50 microM, 24-h exposures) and, importantly, also selectively killed freshly collected patient multiple myeloma cells and highly drug-resistant multiple myeloma cell lines. Mechanistic studies indicated that cis-bixin-induced cytotoxicity was greatly attenuated by co-treatment with glutathione or N-acetylcysteine (NAC); whereas fluorescence-activated cell sorting (FACS) assays using the cell-permeable dyes 5-(and-6) chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H(2)DCFDA), or dihydroethidium demonstrated that cis-bixin rapidly induced cellular reactive oxygen species (ROS) in dose- and time-dependent fashions, collectively implicating ROS as contributory to cis-bixin-induced cytotoxicity. In pursuit of potential contributors to ROS imposition by cis-bixin, we found that cis-bixin inhibited both thioredoxin (Trx) and thioredoxin reductase (TrxR1) activities at concentrations comparable to those required for cytotoxicity, implicating the inhibition of these redox enzymes as potentially contributing to its ability to impose cellular ROS and to kill cancer cells. Collectively, our studies indicate that the annatto constituent cis-bixin has intriguing selective antimyeloma activity that appears to be mediated through effects on redox signaling.

  7. Selection of fecal enterococci exhibiting tcrB-mediated copper resistance in pigs fed diets supplemented with copper.

    Science.gov (United States)

    Amachawadi, R G; Shelton, N W; Shi, X; Vinasco, J; Dritz, S S; Tokach, M D; Nelssen, J L; Scott, H M; Nagaraja, T G

    2011-08-15

    Copper, as copper sulfate, is increasingly used as an alternative to in-feed antibiotics for growth promotion in weaned piglets. Acquired copper resistance, conferred by a plasmid-borne, transferable copper resistance (tcrB) gene, has been reported in Enterococcus faecium and E. faecalis. A longitudinal field study was undertaken to determine the relationship between copper supplementation and the prevalence of tcrB-positive enterococci in piglets. The study was done with weaned piglets, housed in 10 pens with 6 piglets per pen, fed diets supplemented with a normal (16.5 ppm; control) or an elevated (125 ppm) level of copper. Fecal samples were randomly collected from three piglets per pen on days 0, 14, 28, and 42 and plated on M-Enterococcus agar, and three enterococcal isolates were obtained from each sample. The overall prevalence of tcrB-positive enterococci was 21.1% (38/180) in piglets fed elevated copper and 2.8% (5/180) in the control. Among the 43 tcrB-positive isolates, 35 were E. faecium and 8 were E. faecalis. The mean MICs of copper for tcrB-negative and tcrB-positive enterococci were 6.2 and 22.2 mM, respectively. The restriction digestion of the genomic DNA of E. faecium or E. faecalis with S1 nuclease yielded a band of ∼194-kbp size to which both tcrB and the erm(B) gene probes hybridized. A conjugation assay demonstrated cotransfer of tcrB and erm(B) genes between E. faecium and E. faecalis strains. The higher prevalence of tcrB-positive enterococci in piglets fed elevated copper compared to that in piglets fed normal copper suggests that supplementation of copper in swine diets selected for resistance.

  8. Neurally-mediated sincope.

    Science.gov (United States)

    Can, I; Cytron, J; Jhanjee, R; Nguyen, J; Benditt, D G

    2009-08-01

    Syncope is a syndrome characterized by a relatively sudden, temporary and self-terminating loss of consciousness; the causes may vary, but they have in common a temporary inadequacy of cerebral nutrient flow, usually due to a fall in systemic arterial pressure. However, while syncope is a common problem, it is only one explanation for episodic transient loss of consciousness (TLOC). Consequently, diagnostic evaluation should start with a broad consideration of real or seemingly real TLOC. Among those patients in whom TLOC is deemed to be due to ''true syncope'', the focus may then reasonably turn to assessing the various possible causes; in this regard, the neurally-mediated syncope syndromes are among the most frequently encountered. There are three common variations: vasovagal syncope (often termed the ''common'' faint), carotid sinus syndrome, and the so-called ''situational faints''. Defining whether the cause is due to a neurally-mediated reflex relies heavily on careful history taking and selected testing (e.g., tilt-test, carotid massage). These steps are important. Despite the fact that neurally-mediated faints are usually relatively benign from a mortality perspective, they are nevertheless only infrequently an isolated event; neurally-mediated syncope tends to recur, and physical injury resulting from falls or accidents, diminished quality-of-life, and possible restriction from employment or avocation are real concerns. Consequently, defining the specific form and developing an effective treatment strategy are crucial. In every case the goal should be to determine the cause of syncope with sufficient confidence to provide patients and family members with a reliable assessment of prognosis, recurrence risk, and treatment options.

  9. Selective enhancement of glutamate-mediated pressor responses after GABAA receptor blockade in the RVLM of sedentary versus spontaneous wheel running rats

    Science.gov (United States)

    Mueller, Patrick J.; Mischel, Nicholas A.

    2012-01-01

    Overactivity of the sympathetic nervous system (SNS) is a hallmark of many cardiovascular diseases. It is also well-known that physical inactivity independently contributes to cardiovascular diseases, likely in part via increased SNS activity. Recent work from our laboratory has demonstrated increased SNS responses in sedentary animals following either direct activation or disinhibition of the rostral ventrolateral medulla (RVLM), an integral cardiovascular brainstem region. These data led us to hypothesize that the interaction between excitation and inhibition of the RVLM is altered in sedentary versus physically active animals. To test this hypothesis, we recorded mean arterial pressure (MAP) and lumbar sympathetic nerve activity (LSNA) in Inactin anesthetized rats that were housed for 8–12 weeks with or without access to a running wheel. Pressor responses to direct activation of the RVLM with glutamate were similar between groups under intact conditions. However, blockade of γ-aminobutyric acid (GABA)A receptors with bicuculline selectively enhanced pressor responses to glutamate in sedentary animals. Interestingly, LSNA responses to glutamate were not enhanced in sedentary versus active animals in the presence or absence of tonic GABAergic tone. These results suggest that sedentary compared to active conditions enhance GABAergic inhibition of glutamate-sensitive neurons in the RVLM that are involved in blood pressure regulation, and by mechanisms that do not involve LSNA. We also speculate that regular physical activity has differential effects on SNS activity to specific vascular beds and may reduce the risk of developing cardiovascular diseases via changes occurring in the RVLM. PMID:23189062

  10. Ponesimod, a selective S1P1 receptor modulator: a potential treatment for multiple sclerosis and other immune-mediated diseases

    Science.gov (United States)

    D’Ambrosio, Daniele; Freedman, Mark S.; Prinz, Joerg

    2016-01-01

    The first oral treatment for relapsing multiple sclerosis, the nonselective sphingosine-1-phosphate receptor (S1PR) modulator fingolimod, led to identification of a pivotal role of sphingosine-1-phosphate and one of its five known receptors, S1P1R, in regulation of lymphocyte trafficking in multiple sclerosis. Modulation of S1P3R, initially thought to cause some of fingolimod’s side effects, prompted the search for novel compounds with high selectivity for S1P1R. Ponesimod is an orally active, selective S1P1R modulator that causes dose-dependent sequestration of lymphocytes in lymphoid organs. In contrast to the long half-life/slow elimination of fingolimod, ponesimod is eliminated within 1 week of discontinuation and its pharmacological effects are rapidly reversible. Clinical data in multiple sclerosis have shown a dose-dependent therapeutic effect of ponesimod and defined 20 mg as a daily dose with desired efficacy, and acceptable safety and tolerability. Phase II clinical data have also shown therapeutic efficacy of ponesimod in psoriasis. These findings have increased our understanding of psoriasis pathogenesis and suggest clinical utility of S1P1R modulation for treatment of various immune-mediated disorders. A gradual dose titration regimen was found to minimize the cardiac effects associated with initiation of ponesimod treatment. Selectivity for S1P1R, rapid onset and reversibility of pharmacological effects, and an optimized titration regimen differentiate ponesimod from fingolimod, and may lead to better safety and tolerability. Ponesimod is currently in phase III clinical development to assess efficacy and safety in relapsing multiple sclerosis. A phase II study is also ongoing to investigate the potential utility of ponesimod in chronic graft versus host disease. PMID:26770667

  11. Study of selective amorphous silicon etching to silicon nitride using a pin-to-plate dielectric barrier discharge in atmospheric pressure

    Science.gov (United States)

    Kyung, Se-Jin; Park, Jae-Beom; Lee, June-Hee; Lim, Jong-Tae; Yeom, Geun-Young

    2007-08-01

    Remote-type atmospheric pressure plasmas were generated using a modified dielectric barrier discharge with the powered electrode consisting of multipins instead of a conventional blank planar plate. For the N2/NF3 gas mixture, a high etch rate of a :Si close to 115nm/s was obtained by adding 300SCCM (SCCM denotes cubic centimeter per minute at STP) of NF3 to N2 [50SLM (standard liters per minute)] at an ac rms voltage of 8.5kV (2.5kW, 30kHz). However, the selectivity of a :Si to Si3N4 was as low as 1.3. A selectivity of a :Si/Si3N4>5.0 could be obtained while maintaining an etch rate of a :Si at 110nm/s by adding 250SCCM CF4 to the N2 (50SLM )/NF3 (300SCCM) mixture through the formation of a C-F polymer layer preferentially on the Si3N4 surface.

  12. Effect of input power and gas pressure on the roughening and selective etching of SiO2/Si surfaces in reactive plasmas

    International Nuclear Information System (INIS)

    Zhong, X. X.; Huang, X. Z.; Tam, E.; Ostrikov, K.; Colpo, P.; Rossi, F.

    2010-01-01

    We report on the application low-temperature plasmas for roughening Si surfaces which is becoming increasingly important for a number of applications ranging from Si quantum dots to cell and protein attachment for devices such as 'laboratory on a chip' and sensors. It is a requirement that Si surface roughening is scalable and is a single-step process. It is shown that the removal of naturally forming SiO 2 can be used to assist in the roughening of the surface using a low-temperature plasma-based etching approach, similar to the commonly used in semiconductor micromanufacturing. It is demonstrated that the selectivity of SiO 2 /Si etching can be easily controlled by tuning the plasma power, working gas pressure, and other discharge parameters. The achieved selectivity ranges from 0.4 to 25.2 thus providing an effective means for the control of surface roughness of Si during the oxide layer removal, which is required for many advance applications in bio- and nanotechnology.

  13. Fast and selective pressurized liquid extraction with simultaneous in cell clean up for the analysis of alkylphenols and bisphenol A in bivalve molluscs.

    Science.gov (United States)

    Salgueiro-González, N; Turnes-Carou, I; Muniategui-Lorenzoa, S; López-Mahía, P; Prada-Rodríguez, D

    2012-12-28

    A novel and green analytical methodology for the determination of alkylphenols (4-tert-octylphenol, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol technical mixture) and bisphenol A in bivalve mollusc samples was developed and validated. The method was based on selective pressurized liquid extraction (SPLE) with a simultaneous in cell clean up combined with liquid chromatography–electrospray ionization tandem mass spectrometry in negative mode (LC–ESI-MS/MS). Quantitation was performed by standard addition curves in order to correct matrix effects. The analytical features of the method were satisfactory: relative recoveries varied between 80 and 107% and repeatability and intermediate precision were MQL) ranged between 0.34 (4-n-octylphenol) and 3.6 ng g(−1) dry weight (nonylphenol). The main advantages of the method are sensitivity, selectivity, automaticity, low volumes of solvents required and low sample analysis time (according with the principles of Green Chemistry). The method was applied to the analysis of mussel samples of Galicia coast (NW of Spain). Nonylphenol and 4-tert-octylphenol were measured in all samples at concentrations between 9.3 and 372 ng g(−1) dw. As an approach, the human daily intake of these compounds was estimated and no risk for human health was found.

  14. Selective survival rescue in 15-lipoxygenase-1-deficient retinal pigment epithelial cells by the novel docosahexaenoic acid-derived mediator, neuroprotectin D1.

    Science.gov (United States)

    Calandria, Jorgelina M; Marcheselli, Victor L; Mukherjee, Pranab K; Uddin, Jasim; Winkler, Jeremy W; Petasis, Nicos A; Bazan, Nicolas G

    2009-06-26

    The integrity of the retinal pigment epithelial (RPE) cell is essential for the survival of rod and cone photoreceptor cells. Several stressors, including reactive oxygen species, trigger apoptotic damage in RPE cells preceded by an anti-inflammatory, pro-survival response, the formation of neuroprotectin D1 (NPD1), an oxygenation product derived from the essential omega-3 fatty acid family member docosahexaenoic acid. To define the ability of NPD1 and other endogenous novel lipid mediators in cell survival, we generated a stable knockdown human RPE (ARPE-19) cell line using short hairpin RNA to target 15-lipoxygenase-1. The 15-lipoxygenase-1-deficient cells exhibited 30% of the protein expression, and 15-lipoxygenase-2 remained unchanged, as compared with an ARPE-19 cell line control established using nonspecific short hairpin RNA transfected cells. NPD1 synthesis was stimulated by tumor necrosis factor alpha/H2O2-mediated oxidative stress in nonspecific cells (controls), whereas in silenced cells, negligible amounts of NPD1, 12(S)- and 15(S)-hydroxyeicosatetraenoic acid, and lipoxin A4 were found under these conditions. Neither control nor the deficient cells showed an increase in 15-lipoxygenase-1 protein content after 16 h of oxidative stress, suggesting that the increased activity of 15-lipoxygenase-1 is due to activation of pre-existing proteins. 15-Lipoxygenase-silenced cells also displayed an exacerbated sensitivity to oxidative stress-induced apoptosis when compared with the control cells. NPD1 selectively and potently rescued 15-lipoxygenase-silenced cells from oxidative stress-induced apoptosis. These results demonstrate that 15-lipoxygenase-1 is activated by oxidative stress in ARPE-19 cells and that NPD1 is part of an early survival signaling in RPE cells.

  15. Selective Survival Rescue in 15-Lipoxygenase-1-deficient Retinal Pigment Epithelial Cells by the Novel Docosahexaenoic Acid-derived Mediator, Neuroprotectin D1*

    Science.gov (United States)

    Calandria, Jorgelina M.; Marcheselli, Victor L.; Mukherjee, Pranab K.; Uddin, Jasim; Winkler, Jeremy W.; Petasis, Nicos A.; Bazan, Nicolas G.

    2009-01-01

    The integrity of the retinal pigment epithelial (RPE) cell is essential for the survival of rod and cone photoreceptor cells. Several stressors, including reactive oxygen species, trigger apoptotic damage in RPE cells preceded by an anti-inflammatory, pro-survival response, the formation of neuroprotectin D1 (NPD1), an oxygenation product derived from the essential omega-3 fatty acid family member docosahexaenoic acid. To define the ability of NPD1 and other endogenous novel lipid mediators in cell survival, we generated a stable knockdown human RPE (ARPE-19) cell line using short hairpin RNA to target 15-lipoxygenase-1. The 15-lipoxygenase-1-deficient cells exhibited 30% of the protein expression, and 15-lipoxygenase-2 remained unchanged, as compared with an ARPE-19 cell line control established using nonspecific short hairpin RNA transfected cells. NPD1 synthesis was stimulated by tumor necrosis factor α/H2O2-mediated oxidative stress in nonspecific cells (controls), whereas in silenced cells, negligible amounts of NPD1, 12(S)- and 15(S)-hydroxyeicosatetraenoic acid, and lipoxin A4 were found under these conditions. Neither control nor the deficient cells showed an increase in 15-lipoxygenase-1 protein content after 16 h of oxidative stress, suggesting that the increased activity of 15-lipoxygenase-1 is due to activation of pre-existing proteins. 15-Lipoxygenase-silenced cells also displayed an exacerbated sensitivity to oxidative stress-induced apoptosis when compared with the control cells. NPD1 selectively and potently rescued 15-lipoxygenase-silenced cells from oxidative stress-induced apoptosis. These results demonstrate that 15-lipoxygenase-1 is activated by oxidative stress in ARPE-19 cells and that NPD1 is part of an early survival signaling in RPE cells. PMID:19403949

  16. 45 CFR 16.18 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Mediation. 16.18 Section 16.18 Public Welfare... BOARD § 16.18 Mediation. (a) In cases pending before the Board. If the Board decides that mediation... mediation techniques and will provide or assist in selecting a mediator. The mediator may take any steps...

  17. The role of genetic diversity and past-history selection pressures in the susceptibility of Chironomus riparius populations to environmental stress.

    Science.gov (United States)

    Pedrosa, João A M; Cocchiararo, Berardino; Bordalo, Maria D; Rodrigues, Andreia C M; Soares, Amadeu M V M; Barata, Carlos; Nowak, Carsten; Pestana, João L T

    2017-01-15

    Natural populations experiencing intense selection and genetic drift may exhibit limited potential to adapt to environmental change. The present study addresses the following aspects of the "genetic erosion" hypothesis in the midge Chironomus riparius: does long-term mercury (Hg) contamination affect the Hg tolerance of midge populations inhabiting such impacted areas? If so, is there any fitness cost under changing environmental conditions? And does genetic impoverishment influence the susceptibility of C. riparius to cope with environmental stressful conditions? For this end, we tested the acute and chronic tolerance to Hg and salinity in four C. riparius populations differing in their levels of genetic diversity (assessed through microsatellite markers) and past-histories of Hg exposure. Results showed that the midge population collected from a heavily Hg-contaminated site had higher Hg tolerance compared to the population collected from a closely-located reference site suggesting directional selection for Hg-tolerant traits in its native environment despite no genetic erosion in the field. No increased susceptibility under changing environmental conditions of salinity stress was observed. Moreover, results also showed that populations with higher genetic diversity performed better in the partial life-cycle assays providing evidence on the key role that genetic diversity plays as mediator of populations' susceptibility to environmental stress. Our findings are discussed in terms of the suitability of C. riparius as a model organism in evolutionary toxicology studies as well as the validity of ecotoxicological assessments using genetically eroded laboratory populations. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. The effect of feed supplementation with zinc chelate and zinc sulphate on selected humoral and cell-mediated immune parameters and cytokine concentration in broiler chickens.

    Science.gov (United States)

    Jarosz, Łukasz; Marek, Agnieszka; Grądzki, Zbigniew; Kwiecień, Małgorzata; Kalinowski, Marcin

    2017-06-01

    The ability of poultry to withstand infectious disease caused by bacteria, viruses or protozoa depends upon the integrity of the immune system. Zinc is important for proper functioning of heterophils, mononuclear phagocytes and T lymphocytes. Numerous data indicate that the demand for zinc in poultry is not met in Poland due to its low content in feeds of vegetable origin. The aim of the study was to determine the effect of supplementation of inorganic (ZnSO 4 and ZnSO 4 + phytase enzyme), and organic forms of zinc (Zn with glycine and Zn with glycine and phytase enzyme) on selected parameters of the cellular and humoral immune response in broiler chickens by evaluating the percentage of CD3 + CD4 + , CD3 + CD8 + , CD25 + , MHC Class II, and BU-1 + lymphocytes, the phagocytic activity of monocytes and heterophils, and the concentration of IL-2, IL-10 and TNF-α in the peripheral blood. Flow cytometry was used to determine selected cell-mediated immune response parameters. Phagocytic activity in whole blood was performed using the commercial Phagotest kit (ORPEGEN-Pharma, Immuniq, Poland). The results showed that supplementation with zinc chelates causes activation of the cellular and humoral immune response in poultry, helping to maintain the balance between the Th1 and Th2 response and enhancing resistance to infections. In contrast with chelates, the use of zinc in the form of sulphates has no immunomodulatory effect and may contribute to the development of local inflammatory processes in the digestive tract, increasing susceptibility to infection. Copyright © 2016. Published by Elsevier Ltd.

  19. SacB-SacR gene cassette as the negative selection marker to suppress Agrobacterium overgrowth in Agrobacterium-mediated plant transformation

    Directory of Open Access Journals (Sweden)

    Yiming Liu

    2016-10-01

    Full Text Available Agrobacterium overgrowth is a common problem in Agrobacterium-mediated plant transfor-mation. To suppress the Agrobacterium overgrowth, various antibiotics have been used during plant tissue culture steps. The antibiotics are expensive and may adversely affect plant cell differentiation and reduce plant transformation efficiency. The SacB-SacR proteins are toxic to most Agrobacterium tumefaciens strains when they are grown on culture medium sup¬plemented with sucrose. Therefore, SacB-SacR genes can be used as negative selection markers to suppress the overgrowth of Agrobacterium tumefaciens in the plant tissue culture process. We generated a mutant Agrobacterium tumefaciens strain GV2260 (recA-SacB/R that has the SacB-SacR cassette inserted into the bacterial genome at the recA gene locus. The mutant Agrobacterium strain is sensitive to sucrose but maintains its ability to transform plant cells in both transient and stable transformation assays. We demonstrated that the mutant strain GV2260 (recA-SacB/R can be inhibited by sucrose that reduces the overgrowth of Agrobacterium and therefore improves the plant transformation efficiency. We employed GV2260 (recA-SacB/R to generate stable transgenic N. benthamiana plants expressing a CRISPR-Cas9 for knocking out a WRKY transcrip¬tion factor.

  20. Distinguishing HIV-1 drug resistance, accessory, and viral fitness mutations using conditional selection pressure analysis of treated versus untreated patient samples

    Directory of Open Access Journals (Sweden)

    Lee Christopher

    2006-05-01

    Full Text Available Abstract Background HIV can evolve drug resistance rapidly in response to new drug treatments, often through a combination of multiple mutations 123. It would be useful to develop automated analyses of HIV sequence polymorphism that are able to predict drug resistance mutations, and to distinguish different types of functional roles among such mutations, for example, those that directly cause drug resistance, versus those that play an accessory role. Detecting functional interactions between mutations is essential for this classification. We have adapted a well-known measure of evolutionary selection pressure (Ka/Ks and developed a conditional Ka/Ks approach to detect important interactions. Results We have applied this analysis to four independent HIV protease sequencing datasets: 50,000 clinical samples sequenced by Specialty Laboratories, Inc.; 1800 samples from patients treated with protease inhibitors; 2600 samples from untreated patients; 400 samples from untreated African patients. We have identified 428 mutation interactions in Specialty dataset with statistical significance and we were able to distinguish primary vs. accessory mutations for many well-studied examples. Amino acid interactions identified by conditional Ka/Ks matched 80 of 92 pair wise interactions found by a completely independent study of HIV protease (p-value for this match is significant: 10-70. Furthermore, Ka/Ks selection pressure results were highly reproducible among these independent datasets, both qualitatively and quantitatively, suggesting that they are detecting real drug-resistance and viral fitness mutations in the wild HIV-1 population. Conclusion Conditional Ka/Ks analysis can detect mutation interactions and distinguish primary vs. accessory mutations in HIV-1. Ka/Ks analysis of treated vs. untreated patient data can distinguish drug-resistance vs. viral fitness mutations. Verification of these results would require longitudinal studies. The result

  1. The selective target of capsaicin on FASN expression and de novo fatty acid synthesis mediated through ROS generation triggers apoptosis in HepG2 cells.

    Directory of Open Access Journals (Sweden)

    Hathaichanok Impheng

    Full Text Available The inhibition of the mammalian de novo synthesis of long-chain saturated fatty acids (LCFAs by blocking the fatty acid synthase (FASN enzyme activity in tumor cells that overexpress FASN can promote apoptosis, without apparent cytotoxic to non-tumor cells. The present study aimed to focus on the potent inhibitory effect of capsaicin on the fatty acid synthesis pathway inducing apoptosis of capsaicin in HepG2 cells. The use of capsaicin as a source for a new FASN inhibitor will provide new insight into its possible application as a selective anti-cancer therapy. The present findings showed that capsaicin promoted apoptosis as well as cell cycle arrest in the G0/G1 phase. The onset of apoptosis was correlated with a dissipation of mitochondrial membrane potential (ΔΨm. Apoptotic induction by capsaicin was mediated by inhibition of FASN protein expression which was accompanied by decreasing its activity on the de novo fatty acid synthesis. The expression of FASN was higher in HepG2 cells than in normal hepatocytes that were resistant to undergoing apoptosis following capsaicin administration. Moreover, the inhibitory effect of capsaicin on FASN expression and activity was found to be mediated by an increase of intracellular reactive oxygen species (ROS generation. Treatment of HepG2 cells with capsaicin failed to alter ACC and ACLY protein expression, suggesting ACC and ACLY might not be the specific targets of capsaicin to induce apoptosis. An accumulation of malonyl-CoA level following FASN inhibition represented a major cause of mitochondrial-dependent apoptotic induction instead of deprivation of fatty acid per se. Here, we also obtained similar results with C75 that exhibited apoptosis induction by reducing the levels of fatty acid without any change in the abundance of FASN expression along with increasing ROS production. Collectively, our results provide novel evidence that capsaicin exhibits a potent anti-cancer property by targeting

  2. Characterization of Carbon-Contaminated B4C-Coated Optics after Chemically Selective Cleaning with Low-Pressure RF Plasma.

    Science.gov (United States)

    Moreno Fernández, H; Rogler, D; Sauthier, G; Thomasset, M; Dietsch, R; Carlino, V; Pellegrin, E

    2018-01-22

    Boron carbide (B 4 C) is one of the few materials that is expected to be most resilient with respect to the extremely high brilliance of the photon beam generated by free electron lasers (FELs) and is thus of considerable interest for optical applications in this field. However, as in the case of many other optics operated at light source facilities, B 4 C-coated optics are subject to ubiquitous carbon contaminations. Carbon contaminations represent a serious issue for the operation of FEL beamlines due to severe reduction of photon flux, beam coherence, creation of destructive interference, and scattering losses. A variety of B 4 C cleaning technologies were developed at different laboratories with varying success. We present a study regarding the low-pressure RF plasma cleaning of carbon contaminated B 4 C test samples via inductively coupled O 2 /Ar, H 2 /Ar, and pure O 2 RF plasma produced following previous studies using the same ibss GV10x downstream plasma source. Results regarding the chemistry, morphology as well as other aspects of the B 4 C optical coating before and after the plasma cleaning are reported. We conclude that among the above plasma processes only plasma based on pure O 2 feedstock gas exhibits the required chemical selectivity for maintaining the integrity of the B 4 C optical coatings.

  3. Trace analysis of selected hormones and sterols in river sediments by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

    Science.gov (United States)

    Matić, Ivana; Grujić, Svetlana; Jauković, Zorica; Laušević, Mila

    2014-10-17

    In this paper, development and optimization of new LC-MS method for determination of twenty selected hormones, human/animal and plant sterols in river sediments were described. Sediment samples were prepared using ultrasonic extraction and clean up with silica gel/anhydrous sodium sulphate cartridge. Extracts were analyzed by liquid chromatography-linear ion trap-tandem mass spectrometry, with atmospheric pressure chemical ionization. The optimized extraction parameters were extraction solvent (methanol), weight of the sediment (2 g) and time of ultrasonic extraction (3× 10 min). Successful chromatographic separation of hormones (estriol and estrone, 17α- and 17β-estradiol) and four human/animal sterols (epicoprostanol, coprostanol, α-cholestanol and β-cholestanol) that have identical fragmentation reactions was achieved. The developed and optimized method provided high recoveries (73-118%), low limits of detection (0.8-18 ng g(-1)) and quantification (2.5-60 ng g(-1)) with the RSDs generally lower than 20%. Applicability of the developed method was confirmed by analysis of six river sediment samples. A widespread occurrence of human/animal and plant sterols was found. The only detected hormone was mestranol in just one sediment sample. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Comparisons of soxhlet extraction, pressurized liquid extraction, supercritical fluid extraction and subcritical water extraction for environmental solids: recovery, selectivity and effects on sample matrix.

    Science.gov (United States)

    Hawthorne, S B; Grabanski, C B; Martin, E; Miller, D J

    2000-09-15

    Extractions of a polycyclic aromatic hydrocarbon (PAH)-contaminated soil from a former manufactured gas plant site were performed with a Soxhlet apparatus (18 h), by pressurized liquid extraction (PLE) (50 min at 100 degrees C), supercritical fluid extraction (SFE) (1 h at 150 degrees C with pure CO2), and subcritical water (1 h at 250 degrees C, or 30 min at 300 degrees C). Although minor differences in recoveries for some PAHs resulted from the different methods, quantitative agreement between all of the methods was generally good. However, the extract quality differed greatly. The organic solvent extracts (Soxhlet and PLE) were much darker, while the extracts from subcritical water (collected in toluene) were orange, and the extracts from SFE (collected in CH2Cl2) were light yellow. The organic solvent extracts also yielded more artifact peaks in the gas chromatography (GC)-mass spectrometry and GC-flame ionization detection chromatograms, especially compared to supercritical CO2. Based on elemental analysis (carbon and nitrogen) of the soil residues after each extraction, subcritical water, PLE, and Soxhlet extraction had poor selectivity for PAHs versus bulk soil organic matter (approximately 1/4 to 1/3 of the bulk soil organic matter was extracted along with the PAHs), while SFE with pure CO2 removed only 8% of the bulk organic matrix. Selectivities for different compound classes also vary with extraction method. Extraction of urban air particulate matter with organic solvents yields very high concentrations of n- and branched alkanes (approximately C18 to C30) from diesel exhaust as well as lower levels of PAHs, and no selectivity between the bulk alkanes and PAHs is obtained during organic solvent extraction. Some moderate selectivity with supercritical CO2 can be achieved by first extracting the bulk alkanes at mild conditions, followed by stronger conditions to extract the remaining PAHs, i.e., the least polar organics are the easiest organics to extract

  5. Temperature, pressure, and size dependence of Pd-H interaction in size selected Pd-Ag and Pd-Cu alloy nanoparticles: In-situ X-ray diffraction studies

    Energy Technology Data Exchange (ETDEWEB)

    Sengar, Saurabh K.; Mehta, B. R., E-mail: brmehta@physics.iitd.ac.in [Thin Film Laboratory, Department of Physics, Indian Institute of Technology Delhi, New Delhi 110016 (India); Kulriya, P. K. [Inter University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi 110067 (India)

    2014-03-21

    In this study, in-situ X-ray diffraction has been carried out to investigate the effect of temperature and pressure on hydrogen induced lattice parameter variation in size selected Pd-Ag and Pd-Cu alloy nanoparticles. The nanoparticles of three different mobility equivalent diameters (20, 40, and 60 nm) having a narrow size distribution were prepared by gas phase synthesis method. In the present range of temperature (350 K to 250 K) and pressure (10{sup −4} to 100 millibars), no α (H/Pd ≤ 0.03) ↔ β (H/Pd ≥ 0.54) phase transition is observed. At temperature higher than 300 °C or pressure lower than 25 millibars, there is a large difference in the rate at which lattice constant varies as a function of pressure and temperature. Further, the lattice variation with temperature and pressure is also observed to depend upon the nanoparticle size. At lower temperature or higher pressure, size of the nanoparticle seems to be relatively less important. These results are explained on the basis of the relative dominance of physical absorption and diffusion of H in Pd alloy nanoparticles at different temperature and pressure. In the present study, absence of α ↔ β phase transition points towards the advantage of using Pd-alloy nanoparticles in applications requiring long term and repeated hydrogen cycling.

  6. The Impact of Green Supply Chain Management Practices on Performance: Moderating Role of Institutional Pressure with Mediating Effect of Green Innovation

    Directory of Open Access Journals (Sweden)

    Muhammad Shafique

    2017-06-01

    Full Text Available Green supply chain management (GSCM, a cross-disciplinary field has grown during recent years with increasing interest from both academia and industry. GSCM considers emphasizing environmental issues in Traditional Supply Chain Management (TSCM. Due to the new trends in global warming, environmental sustainability has become a greater concern among the organizations and enterprises globally. This study will focus on green supply chain management practices in the presence of green innovation. Green innovation will improve organizational processes as well as products, which lead to economic and environmental performance. Different institutional actors are putting pressures to implement Green supply chain management practices. Population of this study is electronics industry in Pakistan. Sample size is 500 with cluster sampling technique. Data has been collected through a survey method based on the adopted questionnaire. The collected data will be tested through Cronbach Alpha, Descriptive Statistics, Pearson Correlation, Linear Regression, Moderated Regression, Multiple Logistic Regression and Hayes’s statistical tests to analyse the suggested research model. This study will enable organizations to implement green supply chain management practices to bear institutional pressure and move towards green innovation to enhance their economic and environmental performance that were never possible before this study.

  7. Detecting Site-Specific Physicochemical Selective Pressures: Applications to the Class I HLA of the Human Major Histocompatibility Complex and the SRK of the Plant Sporophytic Self-Incompatibility System

    DEFF Research Database (Denmark)

    Sainudiin, Raazesh; Wong, Wendy Shuk Wan; Yogeeswaran, Krithika

    2005-01-01

    plants (Brassicaceae), whose structure is unknown. Through likelihood ratio tests we demonstrate that at some sites, the positively selected MHC and SRK proteins are under physicochemical selective pressures to alter polarity, volume, polarity and/or volume, and charge to various extents. An empirical......:transversion biases. Here, we apply this method to two positively selected receptors involved in ligand-recognition: the class I alleles of the human major histocompatibility complex (MHC) of known structure and the S-locus receptor kinase (SRK) of the sporophytic self-incompatibility system (SSI) in cruciferous...

  8. Identification of Outlier Loci Responding to Anthropogenic and Natural Selection Pressure in Stream Insects Based on a Self-Organizing Map

    Directory of Open Access Journals (Sweden)

    Bin Li

    2016-05-01

    Full Text Available Water quality maintenance should be considered from an ecological perspective since water is a substrate ingredient in the biogeochemical cycle and is closely linked with ecosystem functioning and services. Addressing the status of live organisms in aquatic ecosystems is a critical issue for appropriate prediction and water quality management. Recently, genetic changes in biological organisms have garnered more attention due to their in-depth expression of environmental stress on aquatic ecosystems in an integrative manner. We demonstrate that genetic diversity would adaptively respond to environmental constraints in this study. We applied a self-organizing map (SOM to characterize complex Amplified Fragment Length Polymorphisms (AFLP of aquatic insects in six streams in Japan with natural and anthropogenic variability. After SOM training, the loci compositions of aquatic insects effectively responded to environmental selection pressure. To measure how important the role of loci compositions was in the population division, we altered the AFLP data by flipping the existence of given loci individual by individual. Subsequently we recognized the cluster change of the individuals with altered data using the trained SOM. Based on SOM recognition of these altered data, we determined the outlier loci (over 90th percentile that showed drastic changes in their belonging clusters (D. Subsequently environmental responsiveness (Ek’ was also calculated to address relationships with outliers in different species. Outlier loci were sensitive to slightly polluted conditions including Chl-a, NH4-N, NOX-N, PO4-P, and SS, and the food material, epilithon. Natural environmental factors such as altitude and sediment additionally showed relationships with outliers in somewhat lower levels. Poly-loci like responsiveness was detected in adapting to environmental constraints. SOM training followed by recognition shed light on developing algorithms de novo to

  9. Optimization of selective pressurized liquid extraction for extraction and in-cell clean-up of PCDD/Fs in soils and sediments.

    Science.gov (United States)

    Do, Lan; Lundstedt, Staffan; Haglund, Peter

    2013-03-01

    This paper describes the development of methods for selective extraction of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) from soils and sediments, using pressurized liquid extraction with in-cell clean-up (SPLE). Two binary solvent mixtures, viz. dichloromethane/n-heptane (DCM/Hp), and diethylether/n-heptane (DEE/Hp), were evaluated. The SPLE extraction conditions were optimized using central composite face (CCF) design. Three factors were investigated: extraction temperature (60-160 °C), number of extraction cycles (1-3) and time per cycle (2-18 min). The results showed that DCM/Hp (1/1, v/v) and DEE/Hp (1/2, v/v) were the best extraction solvent compositions and that the extraction temperature was a critical factor that needed careful optimization to achieve high extraction efficiency without co-extraction of sulfuric acid. Under the optimal conditions, the SPLE methods provided results with good accuracy and precision. For the sandy soil certified reference material (CRM-529) the quantification results ended up in the range 82-110% as compared to the concentrations obtained by a reference method based on Soxhlet extraction and external column clean-up. Furthermore, for a clay soil (CRM-530) and a sediment reference material (WMS-01), the accuracy (trueness) of the TEQ values were +11% (DCM/Hp) and +8% (DEE/Hp) for CRM-530, +8% and -7% for WMS-01, respectively. The individual congener concentrations also agreed well with the certified values. These findings show that SPLE is a promising method for combined extraction and clean-up of PCDD/Fs in soil/sediment samples. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. SacB-SacR gene cassette as the negative selection marker to suppress Agrobacterium overgrowth in Agrobacterium-mediated plant transformation

    Science.gov (United States)

    Agrobacterium overgrowth is a common problem in Agrobacterium-mediated plant transformation. To suppress the Agrobacterium overgrowth, various antibiotics have been used during plant tissue culture steps. The antibiotics are expensive and may adversely affect plant cell differentiation and reduce ...

  11. Glycogen synthase kinase-3 inhibitors suppress the AR-V7-mediated transcription and selectively inhibit cell growth in AR-V7-positive prostate cancer cells.

    Science.gov (United States)

    Nakata, Daisuke; Koyama, Ryokichi; Nakayama, Kazuhide; Kitazawa, Satoshi; Watanabe, Tatsuya; Hara, Takahito

    2017-06-01

    Recent evidence suggests that androgen receptor (AR) splice variants, including AR-V7, play a pivotal role in resistance to androgen blockade in prostate cancer treatment. The development of new therapeutic agents that can suppress the transcriptional activities of AR splice variants has been anticipated as the next generation treatment of castration-resistant prostate cancer. High-throughput screening of AR-V7 signaling inhibitors was performed using an AR-V7 reporter system. The effects of a glycogen synthase kinase-3 (GSK3) inhibitor, LY-2090314, on endogenous AR-V7 signaling were evaluated in an AR-V7-positive cell line, JDCaP-hr, by quantitative reverse transcription polymerase chain reaction. The relationship between AR-V7 signaling and β-catenin signaling was assessed using RNA interference. The effect of LY-2090314 on cell growth in various prostate cancer cell lines was also evaluated. We identified GSK3 inhibitors as transcriptional suppressors of AR-V7 using a high-throughput screen with an AR-V7 reporter system. LY-2090314 suppressed the reporter activity and endogenous AR-V7 activity in JDCaP-hr cells. Because silencing of β-catenin partly rescued the suppression, it was evident that the suppression was mediated, at least partially, via the activation of β-catenin signaling. AR-V7 signaling and β-catenin signaling reciprocally regulate each other in JDCaP-hr cells, and therefore, GSK3 inhibition can repress AR-V7 transcriptional activity by accumulating intracellular β-catenin. Notably, LY-2090314 selectively inhibited the growth of AR-V7-positive prostate cancer cells in vitro. Our findings demonstrate the potential of GSK3 inhibitors in treating advanced prostate cancer driven by AR splice variants. In vivo evaluation of AR splice variant-positive prostate cancer models will help illustrate the overall significance of GSK3 inhibitors in treating prostate cancer. © 2017 Wiley Periodicals, Inc.

  12. Pressurized water versus ethanol as a Silybum marianum extraction solvent for inhibition of low-density lipoprotein oxidation mediated by copper and J774 macrophage cells.

    Science.gov (United States)

    Wallace, Sunny N; Raible, Jennifer; Carrier, Danielle Julie; Vaughn, Katherine L; Griffis, Carl L; Clausen, Edgar C; Nagarajan, Shanmugam

    2007-09-01

    Silybum marianum contains flavonolignans, termed silymarin (SM), that are therapeutic agents for many inflammation-based diseases including atherosclerosis. Oxidation of human low-density lipoprotein was induced by CuSO4 or J774 macrophage cells and measured by the formation of thiobarbituric acid reactive substances (TBARS). SM was extracted by pressurized hot water (PHWE) or ethanol, and the effects of these extracts on TBARS formation were evaluated in comparison with those of SM preparations made from blending masses of individual flavonolignan standards in ratios identical to those of the water and ethanol extracts. Ethanol-extracted SM and its blended counterpart inhibited the generation of TBARS by 82% and 43%, respectively, at 150 mumol/L doses. TBARS levels in the presence of 150 micromol/L of the PHWE and its blended SM counterpart were reduced by 84% and 38%, respectively. Extracts from milk thistle fruit displayed higher protective effects than blended SM solutions of the same concentration with an identical compositional makeup. The appearance of degradation peaks in the water extract did not create any cytotoxic effects. Results of this study confirm that PHWE can be used to extract flavonolignans from milk thistle and that these extracts may possess therapeutic potential different from or beyond that of traditional organic solvent preparations.

  13. Spin-lattice-coupling-mediated magnetoferroelectric phase transition induced by uniaxial pressure in multiferroic CuFe1 -xMxO2 (M =Ga , Al)

    Science.gov (United States)

    Tamatsukuri, Hiromu; Mitsuda, Setsuo; Nakamura, Tenfu; Takata, Kouhei; Nakajima, Taro; Prokes, Karel; Yokaichiya, Fabiano; Kiefer, Klaus

    2017-05-01

    We have investigated magnetic and ferroelectric (dielectric) properties of multiferroic CuFe0.982Ga0.018O2 , CuFe0.965Ga0.035O2 , and CuFe0.95Al0.05O2 under applied uniaxial pressure p up to 600 MPa. Unlike the results of the almost same experiments on CuFeO2 [Tamatsukuri et al., Phys. Rev. B 94, 174402 (2016), 10.1103/PhysRevB.94.174402], we have found that the application of p induces a new ferroelectric phase, which is different from the well-studied spin-driven ferroelectric phase with helical magnetic ordering, in all the doped samples investigated here. We have also constructed the temperature versus p magnetoelectric phase diagrams of the three samples. The ferroelectric polarization in the p -induced ferroelectric phase lies along the [110] direction as in the helical magnetoferroelectric phase, and its value is comparable with or larger than that in the helical magnetoferroelectric phase. The magnetic structure in the p -induced ferroelectric phase seems to be of a collinear sinusoidal type. Although this magnetic structure itself does not break the inversion symmetry, it is considered to play an important role in the origin of ferroelectricity in the p -induced ferroelectric phase through the spin-lattice coupling in this system.

  14. COMPARISONS OF SOXHLET EXTRACTION, PRESSURIZED LIQUID EXTRACTION, SUPERCRITICAL FLUID EXTRACTION, AND SUBCRITICAL WATER EXTRACTION FOR ENVIRONMENTAL SOLIDS: RECOVERY, SELECTIVITY, AND EFFECTS ON SAMPLE MATRIX. (R825394)

    Science.gov (United States)

    Extractions of a polycyclic aromatic hydrocarbon (PAH)-contaminated soil from a former manufactured gas plant site were performed with a Soxhlet apparatus (18 h), by pressurized liquid extraction (PLE) (50 min at 100°C), supercritical fluid extraction (SFE) (1 h at 150°...

  15. Selective oxidation

    International Nuclear Information System (INIS)

    Cortes Henao, Luis F.; Castro F, Carlos A.

    2000-01-01

    It is presented a revision and discussion about the characteristics and factors that relate activity and selectivity in the catalytic and not catalytic partial oxidation of methane and the effect of variables as the temperature, pressure and others in the methane conversion to methanol. It thinks about the zeolites use modified for the catalytic oxidation of natural gas

  16. Water-soluble chitosan derivatives and pH-responsive hydrogels by selective C-6 oxidation mediated by TEMPO-laccase redox system

    NARCIS (Netherlands)

    Botelho da Silva, Suse; Krolicka, Malgorzata; Broek, van den Lambertus A.M.; Frissen, August E.; Boeriu, Carmen Gabriela

    2018-01-01

    Chitosan is a polysaccharide with recognized antioxidant, antimicrobial and wound healing activities. However, this polymer is soluble only in dilute acidic solutions, which restricts much of its applications. A usual strategy for improving the functionality of polysaccharides is the selective

  17. Evaluation on the effectiveness of 2-deoxyglucose-6-phosphate phosphatase (DOGR1) gene as a selectable marker for oil palm (Elaeis guineensis Jacq.) embryogenic calli transformation mediated by Agrobacterium tumefaciens

    Science.gov (United States)

    Izawati, Abang Masli Dayang; Masani, Mat Yunus Abdul; Ismanizan, Ismail; Parveez, Ghulam Kadir Ahmad

    2015-01-01

    DOGR1, which encodes 2-deoxyglucose-6-phosphate phosphatase, has been used as a selectable marker gene to produce transgenic plants. In this study, a transformation vector, pBIDOG, which contains the DOGR1 gene, was transformed into oil palm embryogenic calli (EC) mediated by Agrobacterium tumefaciens strain LBA4404. Transformed EC were exposed to 400 mg l-1 2-deoxyglucose (2-DOG) as the selection agent. 2-DOG resistant tissues were regenerated into whole plantlets on various regeneration media containing the same concentration of 2-DOG. The plantlets were later transferred into soil and grown in a biosafety screenhouse. PCR and subsequently Southern blot analyses were carried out to confirm the integration of the transgene in the plantlets. A transformation efficiency of about 1.0% was obtained using DOGR1 gene into the genome of oil palm. This result demonstrates the potential of using combination of DOGR1 gene and 2-DOG for regenerating transgenic oil palm. PMID:26442041

  18. Fischer–Tropsch Synthesis at a Low Pressure on Subnanometer Cobalt Oxide Clusters: The Effect of Cluster Size and Support on Activity and Selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sungsik; Lee, Byeongdu; Seifert, Sönke; Winans, Randall E.; Vajda, Stefan

    2015-05-21

    In this study, the catalytic activity and changes in the oxidation state during the Fischer Tropsch (FT) reaction was investigated on subnanometer size-selected cobalt clusters deposited on oxide (Al2O3, MgO) and carbon-based (ultrananocrystalline diamond UNCD) supports by temperature programmed reaction (TPRx) combined with in-situ grazing-incidence X-ray absorption characterization (GIXAS). The activity and selectivity of ultrasmall cobalt clusters exhibits a very strong dependence on cluster size and support. The evolution of the oxidation state of metal cluster during the reaction reveals that metal-support interaction plays a key role in the reaction.

  19. Phenotypes selected during chronic lung infection in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Ciofu, Oana; Mandsberg, Lotte F; Wang, Hengzhuang

    2012-01-01

    During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated...... the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis....

  20. High-pressure vapor-phase hydrodeoxygenation of lignin-derived oxygenates to hydrocarbons by a PtMo bimetallic catalyst: Product selectivity, reaction pathway, and structural characterization

    Energy Technology Data Exchange (ETDEWEB)

    Yohe, Sara L.; Choudhari, Harshavardhan J.; Mehta, Dhairya D.; Dietrich, Paul J.; Detwiler, Michael D.; Akatay, Cem M.; Stach, Eric A.; Miller, Jeffrey T.; Delgass, W. Nicholas; Agrawal, Rakesh; Ribeiro, Fabio H.

    2016-12-01

    High-pressure, vapor-phase, hydrodeoxygenation (HDO) reactions of dihydroeugenol (2-methoxy-4-propylphenol), as well as other phenolic, lignin-derived compounds, were investigated over a bimetallic platinum and molybdenum catalyst supported on multi-walled carbon nanotubes (5%Pt2.5%Mo/MWCNT). Hydrocarbons were obtained in 100% yield from dihydroeugenol, including 98% yield of the hydrocarbon propylcyclohexane. The final hydrocarbon distribution was shown to be a strong function of hydrogen partial pressure. Kinetic analysis showed three main dihydroeugenol reaction pathways: HDO, hydrogenation, and alkylation. The major pathway occurred via Pt catalyzed hydrogenation of the aromatic ring and methoxy group cleavage to form 4-propylcyclohexanol, then Mo catalyzed removal of the hydroxyl group by dehydration to form propylcyclohexene, followed by hydrogenation of propylcyclohexene on either the Pt or Mo to form the propylcyclohexane. Transalkylation by the methoxy group occurred as a minor side reaction. Catalyst characterization techniques including chemisorption, scanning transmission electron microscopy, X-ray absorption spectroscopy, and X-ray photoelectron spectroscopy were employed to characterize the catalyst structure. Catalyst components identified were Pt particles, bimetallic PtMo particles, a Mo carbide-like phase, and Mo oxide phases.

  1. Does Physical Activity Mediate the Association Between Perceived Neighborhood Aesthetics and Overweight/Obesity Among South African Adults Living in Selected Urban and Rural Communities?

    Science.gov (United States)

    Malambo, Pasmore; Kengne, Andre P; Lambert, Estelle V; De Villiers, Anniza; Puoane, Thandi

    2017-12-01

    To investigate the mediation effects of physical activity (PA) on the relationship between the perceived neighborhood aesthetic environment and overweight/obesity in free-living South Africans. A cross-sectional study of 671 adults aged ≥ 35 years was analyzed. PA was assessed using the validated International Physical Activity Questionnaire. Perceived neighborhood aesthetics was assessed using the Neighborhood Environment Walkability Scale Questionnaire. Of 671 participants, 76.0% were women, 34.1% aged 45-54 years, and 69.2% were overweight or obese. In adjusted logistic regression models, overweight/obesity was significantly associated with neighborhood aesthetics [odds ratio (OR) = 0.68; 95% confidence interval (CI), 0.50-0.93] and PA (OR = 0.65; 95% CI, 0.65-0.90). In expanded multivariable models, overweight/obesity was associated with age 45-55 years (OR = 1.59; 95% CI, 1.05-2.40), female gender (OR = 6.24; 95% CI, 3.95-9.86), tertiary education (OR = 4.05; 95% CI, 1.19-13.86), and urban residence (OR = 2.46; 95% CI, 1.66-3.65). Aesthetics was positively associated with PA; both aesthetics and PA were negatively associated with overweight and obesity. There was no evidence to support a significant mediating effect of PA on the relationship between aesthetics and overweight/obesity. Future studies should consider objective assessment of aesthetics and PA. In addition, future studies should consider using longitudinal design to evaluate food-related environments, which are related to overweight or obesity.

  2. Receptor-mediated inhibition of adenylate cyclase and stimulation of arachidonic acid release in 3T3 fibroblasts. Selective susceptibility to islet-activating protein, pertussis toxin

    International Nuclear Information System (INIS)

    Murayama, T.; Ui, M.

    1985-01-01

    Thrombin exhibited diverse effects on mouse 3T3 fibroblasts. It (a) decreased cAMP in the cell suspension, (b) inhibited adenylate cyclase in the Lubrol-permeabilized cell suspension in a GTP-dependent manner, increased releases of (c) arachidonic acid and (d) inositol from the cell monolayer prelabeled with these labeled compounds, (e) increased 45 Ca 2+ uptake into the cell monolayer, and (f) increased 86 Rb + uptake into the cell monolayer in a ouabain-sensitive manner. Most of the effects were reproduced by bradykinin, platelet-activating factor, and angiotensin II. The receptors for these agonists are thus likely to be linked to three separate effector systems: the adenylate cyclase inhibition, the phosphoinositide breakdown leading to Ca 2+ mobilization and phospholipase A2 activation, and the Na,K-ATPase activation. Among the effects of these agonists, (a), (b), (c), and (e) were abolished, but (d) and (f) were not, by prior treatment of the cells with islet-activating protein (IAP), pertussis toxin, which ADP-ribosylates the Mr = 41,000 protein, the alpha-subunit of the inhibitory guanine nucleotide regulatory protein (Ni), thereby abolishing receptor-mediated inhibition of adenylate cyclase. The effects (a), (c), (d), and (e) of thrombin, but not (b), were mimicked by A23187, a calcium ionophore. The effects of A23187, in contrast to those of receptor agonists, were not affected by the treatment of cells with IAP. Thus, the IAP substrate, the alpha-subunit of Ni, or the protein alike, may play an additional role in signal transduction arising from the Ca 2+ -mobilizing receptors, probably mediating process(es) distal to phosphoinositide breakdown and proximal to Ca 2+ gating

  3. Transcriptome-based analyses of phosphite-mediated suppression of rust pathogens Puccinia emaculata and Phakopsora pachyrhizi and functional characterization of selected fungal target genes.

    Science.gov (United States)

    Gill, Upinder S; Sun, Liang; Rustgi, Sachin; Tang, Yuhong; von Wettstein, Diter; Mysore, Kirankumar S

    2018-03-01

    Phosphite (Phi) is used commercially to manage diseases mainly caused by oomycetes, primarily due to its low cost compared with other fungicides and its persistent control of oomycetous pathogens. We explored the use of Phi in controlling the fungal pathogens Puccinia emaculata and Phakopsora pachyrhizi, the causal agents of switchgrass rust and Asian soybean rust, respectively. Phi primes host defenses and efficiently inhibits the growth of P. emaculata, P. pachyrhizi and several other fungal pathogens tested. To understand these Phi-mediated effects, a detailed molecular analysis was undertaken in both the host and the pathogen. Transcriptomic studies in switchgrass revealed that Phi activates plant defense signaling as early as 1 h after application by increasing the expression of several cytoplasmic and membrane receptor-like kinases and defense-related genes within 24 h of application. Unlike in oomycetes, RNA sequencing of P. emaculata and P. pachyrhizi did not exhibit Phi-mediated retardation of cell wall biosynthesis. The genes with reduced expression in either or both rust fungi belonged to functional categories such as ribosomal protein, actin, RNA-dependent RNA polymerase, and aldehyde dehydrogenase. A few P. emaculata genes that had reduced expression upon Phi treatment were further characterized. Application of double-stranded RNAs specific to P. emaculata genes encoding glutamate N-acetyltransferase and cystathionine gamma-synthase to switchgrass leaves resulted in reduced disease severity upon P. emaculata inoculation, suggesting their role in pathogen survival and/or pathogenesis. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

  4. Lipase AKG mediated resolutions of alpha,alpha-disubstituted 1,2-diols in organic solvents; Remarkably high regio- and enantio-selectivity

    NARCIS (Netherlands)

    Hof, RP; Kellogg, RM

    1996-01-01

    Diols 1, which contain adjacent tertiary and primary hydroxy groups, can be selectively mono-acylated at the primary hydroxy group by many lipases in organic solvents, Since the reaction does not take place at the chiral tertiary centre itself, observed enantioselectivities are usually low. Only the

  5. Structural Elements in the Gαs and Gαq C Termini That Mediate Selective G Protein-coupled Receptor (GPCR) Signaling*

    Science.gov (United States)

    Semack, Ansley; Sandhu, Manbir; Malik, Rabia U.; Vaidehi, Nagarajan; Sivaramakrishnan, Sivaraj

    2016-01-01

    Although the importance of the C terminus of the α subunit of the heterotrimeric G protein in G protein-coupled receptor (GPCR)-G protein pairing is well established, the structural basis of selective interactions remains unknown. Here, we combine live cell FRET-based measurements and molecular dynamics simulations of the interaction between the GPCR and a peptide derived from the C terminus of the Gα subunit (Gα peptide) to dissect the molecular mechanisms of G protein selectivity. We observe a direct link between Gα peptide binding and stabilization of the GPCR conformational ensemble. We find that cognate and non-cognate Gα peptides show deep and shallow binding, respectively, and in distinct orientations within the GPCR. Binding of the cognate Gα peptide stabilizes the agonist-bound GPCR conformational ensemble resulting in favorable binding energy and lower flexibility of the agonist-GPCR pair. We identify three hot spot residues (Gαs/Gαq-Gln-384/Leu-349, Gln-390/Glu-355, and Glu-392/Asn-357) that contribute to selective interactions between the β2-adrenergic receptor (β2-AR)-Gαs and V1A receptor (V1AR)-Gαq. The Gαs and Gαq peptides adopt different orientations in β2-AR and V1AR, respectively. The β2-AR/Gαs peptide interface is dominated by electrostatic interactions, whereas the V1AR/Gαq peptide interactions are predominantly hydrophobic. Interestingly, our study reveals a role for both favorable and unfavorable interactions in G protein selection. Residue Glu-355 in Gαq prevents this peptide from interacting strongly with β2-AR. Mutagenesis to the Gαs counterpart (E355Q) imparts a cognate-like interaction. Overall, our study highlights the synergy in molecular dynamics and FRET-based approaches to dissect the structural basis of selective G protein interactions. PMID:27330078

  6. Structural Elements in the Gαs and Gαq C Termini That Mediate Selective G Protein-coupled Receptor (GPCR) Signaling.

    Science.gov (United States)

    Semack, Ansley; Sandhu, Manbir; Malik, Rabia U; Vaidehi, Nagarajan; Sivaramakrishnan, Sivaraj

    2016-08-19

    Although the importance of the C terminus of the α subunit of the heterotrimeric G protein in G protein-coupled receptor (GPCR)-G protein pairing is well established, the structural basis of selective interactions remains unknown. Here, we combine live cell FRET-based measurements and molecular dynamics simulations of the interaction between the GPCR and a peptide derived from the C terminus of the Gα subunit (Gα peptide) to dissect the molecular mechanisms of G protein selectivity. We observe a direct link between Gα peptide binding and stabilization of the GPCR conformational ensemble. We find that cognate and non-cognate Gα peptides show deep and shallow binding, respectively, and in distinct orientations within the GPCR. Binding of the cognate Gα peptide stabilizes the agonist-bound GPCR conformational ensemble resulting in favorable binding energy and lower flexibility of the agonist-GPCR pair. We identify three hot spot residues (Gαs/Gαq-Gln-384/Leu-349, Gln-390/Glu-355, and Glu-392/Asn-357) that contribute to selective interactions between the β2-adrenergic receptor (β2-AR)-Gαs and V1A receptor (V1AR)-Gαq The Gαs and Gαq peptides adopt different orientations in β2-AR and V1AR, respectively. The β2-AR/Gαs peptide interface is dominated by electrostatic interactions, whereas the V1AR/Gαq peptide interactions are predominantly hydrophobic. Interestingly, our study reveals a role for both favorable and unfavorable interactions in G protein selection. Residue Glu-355 in Gαq prevents this peptide from interacting strongly with β2-AR. Mutagenesis to the Gαs counterpart (E355Q) imparts a cognate-like interaction. Overall, our study highlights the synergy in molecular dynamics and FRET-based approaches to dissect the structural basis of selective G protein interactions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Pressure Sores

    Science.gov (United States)

    Pressure sores are areas of damaged skin caused by staying in one position for too long. They ... wheelchair, or are unable to change your position. Pressure sores can cause serious infections, some of which ...

  8. Evidence of uneven selective pressure on different subsets of the conserved human genome; implications for the significance of intronic and intergenic DNA

    Directory of Open Access Journals (Sweden)

    MacKenzie Alasdair

    2009-12-01

    Full Text Available Abstract Background Human genetic variation produces the wide range of phenotypic differences that make us individual. However, little is known about the distribution of variation in the most conserved functional regions of the human genome. We examined whether different subsets of the conserved human genome have been subjected to similar levels of selective constraint within the human population. We used set theory and high performance computing to carry out an analysis of the density of Single Nucleotide Polymorphisms (SNPs within the evolutionary conserved human genome, at three different selective stringencies, intersected with exonic, intronic and intergenic coordinates. Results We demonstrate that SNP density across the genome is significantly reduced in conserved human sequences. Unexpectedly, we further demonstrate that, despite being conserved to the same degree, SNP density differs significantly between conserved subsets. Thus, both the conserved exonic and intronic genomes contain a significantly reduced density of SNPs compared to the conserved intergenic component. Furthermore the intronic and exonic subsets contain almost identical densities of SNPs indicating that they have been constrained to the same degree. Conclusion Our findings suggest the presence of a selective linkage between the exonic and intronic subsets and ascribes increased significance to the role of introns in human health. In addition, the identification of increased plasticity within the conserved intergenic subset suggests an important role for this subset in the adaptation and diversification of the human population.

  9. The impact of individualised nutritional therapy according to DASH diet on blood pressure, body mass, and selected biochemical parameters in overweight/obese patients with primary arterial hypertension: a prospective randomised study.

    Science.gov (United States)

    Kucharska, Alicja; Gajewska, Danuta; Kiedrowski, Mirosław; Sińska, Beata; Juszczyk, Grzegorz; Czerw, Aleksandra; Augustynowicz, Anna; Bobiński, Krzysztof; Deptała, Andrzej; Niegowska, Joanna

    2018-01-01

    The aim of the study was to assess the impact of individualised nutritional intervention based on the DASH diet (Dietary Approaches to Stop Hypertension) on the nutritional status, blood pressure, and selected biochemical parameters of obese/overweight patients with primary arterial hypertension. A total of 131 participants were randomised to the DASH intervention group (DIG; n = 69, 33 males) or the control group (CG; n = 62, 32 males). A three-month nutritional intervention was carried out in the DIG group, while the control group received only standard recommendations. Body weight, height, waist and hip circumference, body composition, blood pressure, serum glucose, and insulin and leptin concentrations were measured at the baseline and after the intervention. Sixty-four (92.8%) participants in the intervention and 62 (100%) in the control group completed the study. In the DIG group a significant decrease in body mass, systolic and diastolic blood pressure, body fat content, fasting glucose, insulin, and leptin concentrations were observed in comparison to the control group (p DASH dietary intervention provides significant benefits to overweight/obese patients with primary hyper¬tension.

  10. High-pressure tritium

    International Nuclear Information System (INIS)

    Coffin, D.O.

    1976-01-01

    Some solutions to problems of compressing and containing tritium gas to 200 MPa at 700 0 K are discussed. The principal emphasis is on commercial compressors and high-pressure equipment that can be easily modified by the researcher for safe use with tritium. Experience with metal bellows and diaphragm compressors has been favorable. Selection of materials, fittings, and gauges for high-pressure tritium work is also reviewed briefly

  11. Pressure Controller

    Science.gov (United States)

    1981-01-01

    EPIC is Electronic Pressure Indicating Controller produced by North American Manufacturing Company. It is a high-sensitivity device for improving combustion efficiency in industrial furnaces that interprets a signal from a pressure transducer on a furnace and regulates furnace pressure accordingly. A controller can provide savings of from five to 25 percent of an industrial user's annual furnace fuel bill.

  12. Intracranial Pressure

    DEFF Research Database (Denmark)

    Hvedstrup, Jeppe; Radojicic, Aleksandra; Moudrous, Walid

    2018-01-01

    OBJECTIVE: To compare a new method of noninvasive intracranial pressure (nICP) measurement with conventional lumbar puncture (LP) opening pressure. METHODS: In a prospective multicenter study, patients undergoing LP for diagnostic purposes underwent intracranial pressure measurements with HeadSen...

  13. Physicochemical properties of selectively oxidized 1-monolaurin from 2,2,6,6-tetramethyl-1-piperidinyl oxoammonium ion/sodium hypochlorite-mediated reaction.

    Science.gov (United States)

    Ahn, Seon Min; Lee, Hyong Joo; Kim, Sang Woo; Lee, Jaehwan; Chang, Pahn-Shick

    2009-04-08

    The primary alcohol group of 1-monolaurin (1-ML) was selectively oxidized using 2,2,6,6-tetramethyl-1-piperidine oxoammonium ion/sodium hypochlorite (NaOCl) without NaBr at two different conditions. The selective oxidation occurred more efficiently at 35 degrees C and 32.2 mmol of NaOCl than at 25 degrees C and 18.7 mmol of NaOCl. Regioselective oxidation of the primary alcohol without oxidation of a secondary alcohol was confirmed by a chemical shift at 175 ppm and no resonance between 198 and 205 ppm in (13)C NMR and the presence of a peak at 1560-1570 cm(-1) in IR spectra. The water solubility of oxidized 1-monolaurin (OML) was remarkably increased by 33.2 times as compared to that of 1-ML. Creaming velocities resulting from fat flocculation in a 0.2% level of OML and 1-ML were 0.16 and 1.13 mm/h, respectively, implying that OML showed higher efficiency and emulsion stability in preventing fat flocculation than 1-ML due to the selective oxidation of primary alcohol.

  14. Chromatographic selectivity of poly(alkyl methacrylate-co-divinylbenzene) monolithic columns for polar aromatic compounds by pressure-driven capillary liquid chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Shu-Ling; Wang, Chih-Chieh; Fuh, Ming-Ren, E-mail: msfuh@scu.edu.tw

    2016-10-05

    In this study, divinylbenzene (DVB) was used as the cross-linker to prepare alkyl methacrylate (AlMA) monoliths for incorporating π-π interactions between the aromatic analytes and AlMA-DVB monolithic stationary phases in capillary LC analysis. Various AlMA/DVB ratios were investigated to prepare a series of 30% AlMA-DVB monolithic stationary phases in fused-silica capillaries (250-μm i.d.). The physical properties (such as porosity, permeability, and column efficiency) of the synthesized AlMA-DVB monolithic columns were investigated for characterization. Isocratic elution of phenol derivatives was first employed to evaluate the suitability of the prepared AlMA-DVB columns for small molecule separation. The run-to-run (0.16–1.20%, RSD; n = 3) and column-to-column (0.26–2.95%, RSD; n = 3) repeatabilities on retention times were also examined using the selected AlMA-DVB monolithic columns. The π-π interactions between the aromatic ring and the DVB-based stationary phase offered better recognition on polar analytes with aromatic moieties, which resulted in better separation resolution of aromatic analytes on the AlMA-DVB monolithic columns. In order to demonstrate the capability of potential environmental and/or food safety applications, eight phenylurea herbicides with single benzene ring and seven sulfonamide antibiotics with polyaromatic moieties were analyzed using the selected AlMA-DVB monolithic columns. - Highlights: • First investigation on chromatographic selectivity of AlMA-DVB monolithic columns. • Good run-to-run/column-to-column repeatability (<3%) on AlMA-DVB monolithic columns. • Efficient separation of phenylurea herbicides and sulfonamides on AlMA-DVB columns.

  15. DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors.

    Science.gov (United States)

    Narasimhan, Kamesh; Pillay, Shubhadra; Huang, Yong-Heng; Jayabal, Sriram; Udayasuryan, Barath; Veerapandian, Veeramohan; Kolatkar, Prasanna; Cojocaru, Vlad; Pervushin, Konstantin; Jauch, Ralf

    2015-02-18

    Sox2 and Pax6 are transcription factors that direct cell fate decision during neurogenesis, yet the mechanism behind how they cooperate on enhancer DNA elements and regulate gene expression is unclear. By systematically interrogating Sox2 and Pax6 interaction on minimal enhancer elements, we found that cooperative DNA recognition relies on combinatorial nucleotide switches and precisely spaced, but cryptic composite DNA motifs. Surprisingly, all tested Sox and Pax paralogs have the capacity to cooperate on such enhancer elements. NMR and molecular modeling reveal very few direct protein-protein interactions between Sox2 and Pax6, suggesting that cooperative binding is mediated by allosteric interactions propagating through DNA structure. Furthermore, we detected and validated several novel sites in the human genome targeted cooperatively by Sox2 and Pax6. Collectively, we demonstrate that Sox-Pax partnerships have the potential to substantially alter DNA target specificities and likely enable the pleiotropic and context-specific action of these cell-lineage specifiers. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Selective recruitment of Th2-type cells and evasion from a cytotoxic immune response mediated by viral macrophage inhibitory protein-II.

    Science.gov (United States)

    Weber, K S; Gröne, H J; Röcken, M; Klier, C; Gu, S; Wank, R; Proudfoot, A E; Nelson, P J; Weber, C

    2001-08-01

    The viral CC chemokine macrophage inhibitory protein-II (vMIP-II) encoded by human herpes virus 8 (HHV-8) binds to multiple chemokine receptors, however, its ability to control the initial recruitment of specific leukocyte subtypes from the peripheral circulation has not been fully clarified. Here we show that vMIP-II blocks the firm arrest and transmigration of monocytes or Th1-like T lymphocytes triggered by RANTES immobilized on activated human microvascular endothelium (HMVEC) under flow conditions. The internalization of the receptors CCR1 and CCR5 that mediate arrest and transmigration of these cells in response to RANTES was prevented by vMIP-II, supporting its role as an antagonist of CCR1 and CCR5. In contrast, vMIP-II triggered the firm arrest of eosinophils and Th2-like T cells by engaging CCR3, as confirmed by its down-regulation. Immunohistochemical analysis of HHV-8-associated Kaposi's sarcoma lesions marked by vMIP-II expression and mononuclear cell infiltration revealed a predominance of Th2-type CCR3(+) lymphocytes over Th1-type CXCR3(+)/CCR5(+) leukocytes, indicating that as a CCR3 agonist vMIP-II can drive a Th2-type immune response in vivo. Thus, our data provide evidence for a immunomodulatory role of vMIP-II in directing inflammatory cell recruitment away from a Th1-type towards a Th2-type response and thereby facilitating evasion from cytotoxic reactions.

  17. Metformin repositioning as antitumoral agent: selective antiproliferative effects in human glioblastoma stem cells, via inhibition of CLIC1-mediated ion current

    Science.gov (United States)

    Barbieri, Federica; Peretti, Marta; Pizzi, Erika; Pattarozzi, Alessandra; Carra, Elisa; Sirito, Rodolfo; Daga, Antonio; Curmi, Paul M.G.; Mazzanti, Michele; Florio, Tullio

    2014-01-01

    Epidemiological and preclinical studies propose that metformin, a first-line drug for type-2 diabetes, exerts direct antitumor activity. Although several clinical trials are ongoing, the molecular mechanisms of this effect are unknown. Here we show that chloride intracellular channel-1 (CLIC1) is a direct target of metformin in human glioblastoma cells. Metformin exposure induces antiproliferative effects in cancer stem cell-enriched cultures, isolated from three individual WHO grade IV human glioblastomas. These effects phenocopy metformin-mediated inhibition of a chloride current specifically dependent on CLIC1 functional activity. CLIC1 ion channel is preferentially active during the G1-S transition via transient membrane insertion. Metformin inhibition of CLIC1 activity induces G1 arrest of glioblastoma stem cells. This effect was time-dependent, and prolonged treatments caused antiproliferative effects also for low, clinically significant, metformin concentrations. Furthermore, substitution of Arg29 in the putative CLIC1 pore region impairs metformin modulation of channel activity. The lack of drugs affecting cancer stem cell viability is the main cause of therapy failure and tumor relapse. We identified CLIC1 not only as a modulator of cell cycle progression in human glioblastoma stem cells but also as the main target of metformin's antiproliferative activity, paving the way for novel and needed pharmacological approaches to glioblastoma treatment. PMID:25361004

  18. Mediatized Humanitarianism

    DEFF Research Database (Denmark)

    Vestergaard, Anne

    2014-01-01

    The article investigates the implications of mediatization for the legitimation strategies of humanitarian organizations. Based on a (full population) corpus of ~400 pages of brochure material from 1970 to 2007, the micro-textual processes involved in humanitarian organizations' efforts to legiti......The article investigates the implications of mediatization for the legitimation strategies of humanitarian organizations. Based on a (full population) corpus of ~400 pages of brochure material from 1970 to 2007, the micro-textual processes involved in humanitarian organizations' efforts...... legitimation by accountancy, legitimation by institutionalization, and legitimation by compensation. The analysis relates these changes to a problem of trust associated with mediatization through processes of mediation....

  19. Leaf chemistry as a predictor of primate biomass and the mediating role of food selection: a case study in a folivorous lemur (Propithecus verreauxi).

    Science.gov (United States)

    Simmen, Bruno; Tarnaud, Laurent; Marez, André; Hladik, Annette

    2014-06-01

    Folivorous primate biomass has been shown to positively correlate with the average protein-to-fiber ratio in mature leaves of tropical forests. However, studies have failed to explain the mismatch between dietary selection and the role of the protein-to-fiber ratio on primate biomass; why do not folivores always favor mature leaves or leaves with the highest protein-to-fiber ratio? We examined the effect of leaf chemical characteristics and plant abundance (using transect censuses; 0.37 ha, 233 trees) on food choices and nutrient/toxin consumption in a folivorous lemur (Propithecus verreauxi) in a gallery forest in southern Madagascar. To assess the nutritional quality of the habitat, we calculated an abundance-weighted chemical index for each chemical variable. Food intake was quantified using a continuous count of mouthfuls during individual full-day follows across three seasons. We found a significant positive correlation between food ranking in the diet and plant abundance. The protein-to-fiber ratio and most other chemical variables tested had no statistical effect on dietary selection. Numerous chemical characteristics of the sifaka's diet were essentially by-products of generalist feeding and "low energy input/low energy crop" strategy. The examination of feeding behavior and plant chemistry in Old World colobines and folivorous prosimians in Madagascar suggests that relative lack of feeding selectivity and high primate biomass occur when the average protein-to-fiber ratio of mature leaves in the habitat exceeds a threshold at 0.4. © 2013 Wiley Periodicals, Inc.

  20. Human mast cell line-1 (HMC-1) cells transfected with FcεRIα are sensitive to IgE/antigen-mediated stimulation demonstrating selectivity towards cytokine production.

    Science.gov (United States)

    Xia, YuXiu C; Sun, ShanShan; Kuek, Li Eon; Lopata, Andreas L; Hulett, Mark D; Mackay, Graham A

    2011-08-01

    Mast cells play important roles in allergic and inflammatory diseases. Efforts to better understand human mast cell activation and develop novel inhibitory agents have been hampered by the lack of suitable human mast cell lines. The HMC-1 mast cell line has been extensively used, but lacks native expression of the human high-affinity IgE receptor FcεRI limiting its applications. We have stably transfected HMC-1 cells with the IgE-binding α-subunit of FcεRI to generate HMCα cells that are antigen-responsive. We have used flow cytometry, cell signaling assays, pharmacological pathway inhibitors and cell functional assays to characterize the properties of HMCα cells. IgE/antigen responses were compared with those of the adenosine receptor agonist NECA. Surface expression of FcεRI in HMCα cells was demonstrated and was enhanced by prior sensitization with IgE. Activation of HMCα cells with IgE/antigen did not produce degranulation, but did lead to release of numerous cytokines. Whilst there was no measurable increase of intracellular Ca(2+) or marked general changes in protein tyrosine phosphorylation, IgE/antigen stimulation of HMCα cells enhanced phosphorylation of p38(MAPK) and Erk. Inhibitors of these pathways, as well as the src kinase inhibitor PP2, attenuated IgE/antigen-induced cytokine release. In summary, we have generated and characterized HMCα cells and show that they are a useful and relevant human mast cell model to examine FcεRI stabilization, signaling and mediator release. We envisage that HMCα cells will have utility in understanding the importance of mast cells in human allergic disease and in assessing the activity of novel anti-allergic compounds. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Selective secretion of microRNAs from lung cancer cells via extracellular vesicles promotes CAMK1D-mediated tube formation in endothelial cells.

    Science.gov (United States)

    Lawson, James; Dickman, Christopher; MacLellan, Sara; Towle, Rebecca; Jabalee, James; Lam, Stephen; Garnis, Cathie

    2017-10-13

    Extracellular vesicles (EVs) are key signaling mediators between cancer cells and their supporting stroma, and regulate critical processes such as invasion, metastases, and angiogenesis. We have identified a subset of miRNAs (miR-142-3p, miR-143-3p, miR-145-5p, miR-150-5p, miR-223-3p, miR-451a, miR-486-5p, miR-605-5p) that are enriched in lung adenocarcinoma extracellular vesicles compared to the donor cells from which they were derived. Two well-known tumor suppressors, miR-143-3p and miR-145-5p, were also enriched in serum samples collected during surgery from blood vessels draining directly from lung adenocarcinoma tumor beds. Recently, both miRNAs were found to promote neoangiogenesis in endothelial cells in mouse models of lung adenocarcinoma through targeting of CAMK1D, an inhibitory kinase that can impair angiogenesis when over-expressed. We show that the transfer of miR-143-3p and miR-145-5p within extracellular vesicles from lung adenocarcinoma cells to endothelial cells reduces the levels of CAMK1D and increases tube formation by endothelial cells. This finding suggests that transfer of miRNAs within extracellular vesicles is a method of communication between cancer and endothelial cells which promotes angiogenesis while simultaneously removing tumor suppressive miRNAs within the tumor cells, thus driving tumorigenesis.

  2. Co-receptor choice by V alpha14i NKT cells is driven by Th-POK expression rather than avoidance of CD8-mediated negative selection.

    Science.gov (United States)

    Engel, Isaac; Hammond, Kirsten; Sullivan, Barbara A; He, Xi; Taniuchi, Ichiro; Kappes, Dietmar; Kronenberg, Mitchell

    2010-05-10

    Mouse natural killer T (NKT) cells with an invariant V alpha14-J alpha18 rearrangement (V alpha14 invariant [V alpha14i] NKT cells) are either CD4(+)CD8(-) or CD4(-)CD8(-). Because transgenic mice with forced CD8 expression in all T cells exhibited a profound NKT cell deficit, the absence of CD8 has been attributed to negative selection. We now present evidence that CD8 does not serve as a coreceptor for CD1d recognition and that the defect in development in CD8 transgene homozygous mice is the result of a reduction in secondary T cell receptor alpha rearrangements. Thymocytes from mice hemizygous for the CD8 transgene have a less severe rearrangement defect and have functional CD8(+) V alpha14i NKT cells. Furthermore, we demonstrate that the transcription factor Th, Poxviruses and Zinc finger, and Krüppel family (Th-POK) is expressed by V alpha14i NKT cells throughout their differentiation and is necessary both to silence CD8 expression and for the functional maturity of V alpha14i NKT cells. We therefore suggest that Th-POK expression is required for the normal development of V alpha14i NKT cells and that the absence of CD8 expression by these cells is a by-product of such expression, as opposed to the result of negative selection of CD8-expressing V alpha14i NKT cells.

  3. Key role of Ti(IV) in the selective radical-radical cross-coupling mediated by the Ingold-Fischer effect.

    Science.gov (United States)

    Spaccini, Raffaele; Pastori, Nadia; Clerici, Angelo; Punta, Carlo; Porta, Ombretta

    2008-12-31

    We report an innovative approach for the selective synthesis of polyfunctional derivatives by cross-combination of different radicals generated under mild conditions. The coordinating effect of Ti(IV) plays a key role in the reaction mechanism: due to its chelating action on the hydroxyl groups, it promotes the homolytic C-C bond cleavage of alpha,beta-dihydroxy ketones by enhancing the captodative effect and the consequent stabilization of the corresponding alpha-hydroxy-alpha-carbonyl radicals. When these radicals are generated in the presence of stoichiometric amounts of TiCl(4) and 2,2'-azo-bis-isobutyronitrile (AIBN) is employed as a source of alpha-cyanoisopropyl radicals, the selective radical-radical cross-coupling is observed, affording the corresponding beta-hydroxynitriles in high yields. This innovative methodology allows application of the well-known Ingold-Fischer effect to a wider range of stabilized carbon-centered radicals, whose formation derives from the chelating action of Ti(IV).

  4. Emission evaluation of CO 2 and CH4 gases in the selected gas pressure booster station in the Bangestan field of the National Iranian Oil Company

    Directory of Open Access Journals (Sweden)

    Mehdi Ahmadi

    2014-11-01

    Full Text Available Background: Iran is located in the seventh rank in terms of CO2 emissions resulting from the fuel combustion in the world. Gas compressor booster stations, due to the several sources of contaminants, are causing the release of large amounts of CO2 and CH4, which will cause climate change; therefore, estimating the emissions of the gases from oil and gas, different processing units are necessary. Methods: In this study, the emissions factor method, provided by various organizations, was used for determining emissions of CO2 and CH4 from different sources. Results: According to the results obtained, the total amount of CO2 emissions in selected units is from the selected unit and is a significant contribution to the CH4 emissions, so that the whole amount of CO2 emissions is equal to 7739.027 tons per day and the total amount of CH4 emissions is 4 tons per day. Conclusion: Burner has the highest amount of CO2 emissions among the sources of pollutants in the fixed combustion sources; and, the highest emissions of CH4, among the exit gas sources, belong to the process of removing water. Among the exit gas sources-compressors maintenance activities the highest emissions belong to CH4. The amount of CO2 emissions from indirect sources, including electrical equipment in the studied units, are from natural gas fuel which are much more than those from fuel oils for burning. CH4 gas from volatile sources in the gas compressors have the highest emissions compared to other sources.

  5. Positive end expiratory pressure during one-lung ventilation: Selecting ideal patients and ventilator settings with the aim of improving arterial oxygenation

    Directory of Open Access Journals (Sweden)

    Hoftman Nir

    2011-01-01

    Full Text Available The efficacy of positive end-expiratory pressure (PEEP in treating intraoperative hypoxemia during one-lung ventilation (OLV remains in question given conflicting results of prior studies. This study aims to (1 evaluate the efficacy of PEEP during OLV, (2 assess the utility of preoperative predictors of response to PEEP, and (3 explore optimal intraoperative settings that would maximize the effects of PEEP on oxygenation. Forty-one thoracic surgery patients from a single tertiary care university center were prospectively enrolled in this observational study. After induction of general anesthesia, a double-lumen endotracheal tube was fiberoptically positioned and OLV initiated. Intraoperatively, PEEP = 5 and 10 cmH 2 O were sequentially applied to the ventilated lung during OLV. Arterial oxygenation, cardiovascular performance parameters, and proposed perioperative variables that could predict or enhance response to PEEP were analysed. T-test and c2 tests were utilized for continuous and categorical variables, respectively. Multivariate analyses were carried out using a classification tree model of binary recursive partitioning. PEEP improved arterial oxygenation by ≥20% in 29% of patients (n = 12 and failed to do so in 71% (n = 29; however, no cardiovascular impact was noted. Among the proposed clinical predictors, only intraoperative tidal volume per kilogram differed significantly between responders to PEEP and non-responders (mean 6.6 vs. 5.7 ml/kg, P = 0.013; no preoperative variable predicted response to PEEP. A multivariate analysis did not yield a clinically significant model for predicting PEEP responsiveness. PEEP improved oxygenation in a subset of patients; larger, although still protective tidal volumes favored a positive response to PEEP. No preoperative variables, however, could be identified as reliable predictors for PEEP responders.

  6. Complex Mediation

    DEFF Research Database (Denmark)

    Bødker, Susanne; Andersen, Peter Bøgh

    2005-01-01

    This article has its starting point in a large number of empirical findings regarding computer-mediated work. These empirical findings have challenged our understanding of the role of mediation in such work; on the one hand as an aspect of communication and cooperation at work and on the other hand...... as an aspect of human engagement with instruments of work. On the basis of previous work in activity-theoretical and semiotic human—computer interaction, we propose a model to encompass both of these aspects. In a dialogue with our empirical findings we move on to propose a number of types of mediation...... that have helped to enrich our understanding of mediated work and the design of computer mediation for such work....

  7. Genistein mediates the selective radiosensitizing effect in NSCLC A549 cells via inhibiting methylation of the keap1 gene promoter region.

    Science.gov (United States)

    Liu, Xiongxiong; Sun, Chao; Liu, Bingtao; Jin, Xiaodong; Li, Ping; Zheng, Xiaogang; Zhao, Ting; Li, Feifei; Li, Qiang

    2016-05-10

    Non-small cell lung cancer (NSCLC) cells often possess a hypermethylated Keap1 promoter, which decreases Keap1 mRNA and protein expression levels, thus impairing the Nrf2-Keap1 pathway and thereby leading to chemo- or radio-resistance. In this study, we showed that genistein selectively exhibited a radiosensitizing effect on NSCLC A549 cells but not on normal lung fibroblast MRC-5 cells. Genistein caused oxidative stress in A549 cells rather than MRC-5 cells, as determined by the oxidation of the ROS-sensitive probe DCFH-DA and oxidative damage marked by MDA, PCO or 8-OHdG content. In A549 instead of MRC-5 cells, genistein reduced the level of methylation in the Keap1 promoter region, leading to an increased mRNA expression, thus effectively inhibited the transcription of Nrf2 to the nucleus, which suppressed the Nrf2-dependent antioxidant and resulted in the upregulation of ROS. Importantly, when combined with radiation, genistein further increased the ROS levels in A549 cells whereas decreasing the radiation-induced oxidative stress in MRC-5 cells, possibly via increasing the expression levels of Nrf2, GSH and HO-1. Moreover, radiation combined with genistein significantly increased cell apoptosis in A549 but not MRC-5 cells. Together, the results herein show that the intrinsic difference in the redox status of A549 and MRC-5 cells could be the target for genistein to selectively sensitize A549 cells to radiation, thereby leading to an increase in radiosensitivity for A549 cells.

  8. GABA-mediated spatial and temporal asymmetries that contribute to the directionally selective light responses of starburst amacrine cells in retina.

    Science.gov (United States)

    Dmitriev, Andrey V; Gavrikov, Konstantin E; Mangel, Stuart C

    2012-04-01

    Starburst amacrine cells (SACs) are an essential component of the mechanism that generates direction selectivity in the retina. SACs exhibit opposite polarity, directionally selective (DS) light responses, depolarizing to stimuli that move centrifugally away from the cell through the receptive field surround, but hyperpolarizing to stimuli that move centripetally towards the cell through the surround.Recent findings suggest that (1) the intracellular chloride concentration ([Cl(−)](i)) is high in SAC proximal, but low in SAC distal dendritic compartments, so that GABA depolarizes and hyperpolarizes the proximal and distal compartments, respectively, and (2) this [Cl(−)](i) gradient plays an essential role in generating SAC DS light responses. Employing a biophysically realistic, computational model of SACs, which incorporated experimental measurements of SAC electrical properties and GABA and glutamate responses, we further investigated whether and how a [Cl(−)](i) gradient along SAC dendrites produces their DS responses. Our computational analysis suggests that robust DS light responses would be generated in both the SAC soma and distal dendrites if (1) the Cl(−) equilibrium potential is more positive in the proximal dendrite and more negative in the distal dendrite than the resting membrane potential, so that GABA depolarizes and hyperpolarizes the proximal and distal compartments, respectively, and (2) the GABA-evoked increase in the Cl(−) conductance lasts longer than the glutamate-evoked increase in cation conductance. The combination of these two specific GABA-associated spatial and temporal asymmetries, in conjunction with symmetric glutamate excitation, may underlie the opposite polarity, DS light responses of SACs.

  9. Oxidative stress-mediated selective antimicrobial ability of nano-VO2 against Gram-positive bacteria for environmental and biomedical applications