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  1. Strategic addition of an N-linked glycan to a monoclonal antibody improves its HIV-1-neutralizing activity.

    PubMed

    Song, Ruijiang; Oren, Deena A; Franco, David; Seaman, Michael S; Ho, David D

    2013-11-01

    Ibalizumab is a humanized monoclonal antibody that binds human CD4--a key receptor for HIV--and blocks HIV-1 infection. However, HIV-1 strains with mutations resulting in loss of an N-linked glycan from the V5 loop of the envelope glycoprotein gp120 are resistant to ibalizumab. Previous structural analysis suggests that this glycan fills a void between the gp120 V5 loop and the ibalizumab light chain, perhaps causing steric hindrance that disrupts viral entry. If this void contributes to HIV-1 resistance to ibalizumab, we reasoned that 'refilling' it by engineering an N-linked glycan into the ibalizumab light chain at a position spatially proximal to gp120 V5 may restore susceptibility to ibalizumab. Indeed, one such ibalizumab variant neutralized 100% of 118 diverse HIV-1 strains tested in vitro, including 10 strains resistant to parental ibalizumab. These findings demonstrate that the strategic placement of a glycan in the variable region of a monoclonal antibody can substantially enhance its activity.

  2. Strategic addition of an N-linked glycan to a monoclonal antibody improves its HIV-1-neutralizing activity

    PubMed Central

    Song, Ruijiang; Oren, Deena A.; Franco, David; Seaman, Michael S.; Ho, David D.

    2013-01-01

    Ibalizumab is a humanized monoclonal antibody that binds human CD4—a key receptor for HIV—and blocks HIV-1 infection. However, HIV-1 strains with mutations resulting in loss of an N-linked glycan from the V5 loop of the envelope protein gp120 are resistant to ibalizumab. Previous structural analysis suggests that this glycan fills a void between the gp120 V5 loop and the ibalizumab L chain, perhaps causing steric hindrance that disrupts viral entry. If this void contributes to HIV-1 resistance to ibalizumab, we reasoned that ‘refilling’ it by engineering an N-linked glycan into the ibalizumab L chain at a position spatially proximal to gp120 V5 may restore susceptibility to ibalizumab. Indeed, one such ibalizumab variant neutralized 100% of 118 tested diverse HIV-1 strains in vitro, including ten strains resistant to parental ibalizumab. These findings demonstrate that the strategic placement of a glycan in the variable region of a monoclonal antibody can substantially enhance its activity. PMID:24097413

  3. Nanoengineered Additives for Active Coatings

    DTIC Science & Technology

    2007-04-01

    commercial ad bial activ component from the coating, leading to eventual depletion of the film. Small TPU samples were evaluated using a Kirby - Bauer ...7 Table 5. Summary of 24-hr ASTM E 2180 tests with 1 weight-percent additive in PUr (solvent dispersible) based on 6-log loading of...Noveon X-1150). The ASTM E 2180 test is run in triplicate (Note that alternative ro 1° amines) was suspended in dry tetrahydrofuran (THF) (150 mL) in

  4. Linking Smads and transcriptional activation.

    PubMed

    Inman, Gareth J

    2005-02-15

    TGF-beta1 (transforming growth factor-beta1) is the prototypical member of a large family of pleiotropic cytokines that regulate diverse biological processes during development and adult tissue homoeostasis. TGF-beta signals via membrane bound serine/threonine kinase receptors which transmit their signals via the intracellular signalling molecules Smad2, Smad3 and Smad4. These Smads contain conserved MH1 and MH2 domains separated by a flexible linker domain. Smad2 and Smad3 act as kinase substrates for the receptors, and, following phosphorylation, they form complexes with Smad4 and translocate to the nucleus. These Smad complexes regulate gene expression and ultimately determine the biological response to TGF-beta. In this issue of the Biochemical Journal, Wang et al. have shown that, like Smad4, the linker domain of Smad3 contains a Smad transcriptional activation domain. This is capable of recruiting the p300 transcriptional co-activator and is required for Smad3-dependent transcriptional activation. This study raises interesting questions about the nature and regulation of Smad-regulated gene activation and elevates the status of the linker domain to rival that of the much-lauded MH1 and MH2 domains.

  5. Active mineral additives of sapropel ashes

    NASA Astrophysics Data System (ADS)

    Khomich, V. A.; Danilina, E. V.; Krivonos, O. I.; Plaksin, G. V.

    2015-01-01

    The goal of the presented research is to establish a scientific rational for the possibility of sapropel ashes usage as an active mineral additive. The research included the study of producing active mineral additives from sapropels by their thermal treatment at 850900 °C and afterpowdering, the investigation of the properties of paste matrix with an ash additive, and the study of the ash influence on the cement bonding agent. Thermogravimetric analysis and X-ray investigations allowed us to establish that while burning, organic substances are removed, clay minerals are dehydrated and their structure is broken. Sapropel ashes chemical composition was determined. An amorphous ash constituent is mainly formed from silica of the mineral sapropel part and alumosilicagels resulted from clay minerals decomposition. Properties of PC 400 and PC 500A0 sparopel ash additives were studied. Adding ashes containing Glenium plasticizer to the cement increases paste matrix strength and considerably reduces its water absorption. X-ray phase analysis data shows changes in the phase composition of the paste matrix with an ash additive. Ash additives produce a pozzolanic effect on the cement bonding agent. Besides, an ash additive due to the alumosilicagels content causes transformation from unstable calcium aluminate forms to the stable ones.

  6. Displacement Addition on Linking Extensional Fault Arrays in the Canyonlands Graben, Utah

    NASA Astrophysics Data System (ADS)

    Commins, D. C.; Gupta, S.; Cartwright, J. A.; Phillips, W. M.

    2003-12-01

    Studies of brittle fault populations over the past decade have revealed that large extensional faults grow by the lengthening, interaction and physical linkage of en echelon fault segments. However, the temporal evolution of displacement accumulation during segment interaction and linkage is difficult to unravel due to a lack of direct observation during each stage in the fault array development. The process of profile re-adjustment prevents reconstruction of the growth history of a fault from its final configuration, and as a result, several models for the growth trajectory of a fault array undergoing linkage are possible. Observational data with which to constrain the relative timing and mode of displacement accumulation during the linkage process are currently lacking. We use the deformation of late Pleistocene-Holocene stream systems by the growth of a active normal faults in The Grabens, Canyonlands National Park, Utah to constrain the mode of growth of fault arrays. Coupling fault displacement data with geomorphic analysis of deformed present-day and palaeo-streams, permits sequential reconstruction of both simple 2-segment fault arrays and complex multi-segment populations from their initial component segments to the present day displacement geometry. In particular, these data provide information on the relative rates of displacement addition. For example, the presence of waterfalls where streams cross fault scarps indicates abrupt rates of displacement accumulation which we can relate to the hard linkage process. The reconstruction of both three- and six-segment faults reveal common aspects of displacement distribution through time: (1) Displacement accumulation occurs almost entirely in the interaction and linkage phase. (2) Interaction between segments causes enhanced displacement addition in overlap zones. (3) Despite interaction in the soft-linkage stage, faults do not achieve a characteristic profile during this phase (4) Displacement accrues rapidly

  7. Activity Based Curriculum for Elementary Education. Additional Activities, K-6.

    ERIC Educational Resources Information Center

    Wichita Public Schools, KS.

    This elementary curriculum is a vehicle to provide manipulative activities that reinforce academic skills through meaningful, relevant, activity-based awareness of modern society. The twenty-six activity plans included in the curriculum place a major emphasis upon realistic or concrete experiences that deal with the manipulation and exploration of…

  8. Linking Complexity with Cultural Historical Activity Theory

    ERIC Educational Resources Information Center

    McMurtry, Angus

    2006-01-01

    This paper explores the similarities and differences between complexity science's and cultural-historical activity theory's understandings of human learning. Notable similarities include their emphasis on the importance of social systems or collectives in understanding human knowledge and practices, as well as their characterization of systems'…

  9. Linking Europa's plume activity to tides, tectonics, and liquid water

    NASA Astrophysics Data System (ADS)

    Rhoden, Alyssa Rose; Hurford, Terry A.; Roth, Lorenz; Retherford, Kurt

    2015-06-01

    Much of the geologic activity preserved on Europa's icy surface has been attributed to tidal deformation, mainly due to Europa's eccentric orbit. Although the surface is geologically young (30-80 Myr), there is little information as to whether tidally-driven surface processes are ongoing. However, a recent detection of water vapor near Europa's south pole suggests that it may be geologically active. Initial observations indicated that Europa's plume eruptions are time-variable and may be linked to its tidal cycle. Saturn's moon, Enceladus, which shares many similar traits with Europa, displays tidally-modulated plume eruptions, which bolstered this interpretation. However, additional observations of Europa at the same time in its orbit failed to yield a plume detection, casting doubt on the tidal control hypothesis. The purpose of this study is to analyze the timing of plume eruptions within the context of Europa's tidal cycle to determine whether such a link exists and examine the inferred similarities and differences between plume activity on Europa and Enceladus. To do this, we determine the locations and orientations of hypothetical tidally-driven fractures that best match the temporal variability of the plumes observed at Europa. Specifically, we identify model faults that are in tension at the time in Europa's orbit when a plume was detected and in compression at times when the plume was not detected. We find that tidal stress driven solely by eccentricity is incompatible with the observations unless additional mechanisms are controlling the eruption timing or restricting the longevity of the plumes. The addition of obliquity tides, and corresponding precession of the spin pole, can generate a number of model faults that are consistent with the pattern of plume detections. The locations and orientations of these hypothetical source fractures are robust across a broad range of precession rates and spin pole directions. Analysis of the stress variations across

  10. Linking inflammasome activation and phagosome maturation.

    PubMed

    Lazarevic, Vanja; Martinon, Fabio

    2008-04-17

    One-third of the world's population is infected with Mycobacterium tuberculosis, one of the most effective human pathogens, whose success is attributed to the deployment of remarkably sophisticated immune evasion mechanisms. In this issue of Cell Host & Microbe, a new study unravels a novel strategy of immune evasion and enhanced bacterial intracellular survival, which is dependent on inhibition of inflammasome activation by an M. tuberculosis-encoded metalloprotease.

  11. Active semi-supervised community detection based on must-link and cannot-link constraints.

    PubMed

    Cheng, Jianjun; Leng, Mingwei; Li, Longjie; Zhou, Hanhai; Chen, Xiaoyun

    2014-01-01

    Community structure detection is of great importance because it can help in discovering the relationship between the function and the topology structure of a network. Many community detection algorithms have been proposed, but how to incorporate the prior knowledge in the detection process remains a challenging problem. In this paper, we propose a semi-supervised community detection algorithm, which makes full utilization of the must-link and cannot-link constraints to guide the process of community detection and thereby extracts high-quality community structures from networks. To acquire the high-quality must-link and cannot-link constraints, we also propose a semi-supervised component generation algorithm based on active learning, which actively selects nodes with maximum utility for the proposed semi-supervised community detection algorithm step by step, and then generates the must-link and cannot-link constraints by accessing a noiseless oracle. Extensive experiments were carried out, and the experimental results show that the introduction of active learning into the problem of community detection makes a success. Our proposed method can extract high-quality community structures from networks, and significantly outperforms other comparison methods.

  12. Distribution of Prx-linked hydroperoxide reductase activity among microorganisms.

    PubMed

    Takeda, Kouji; Nishiyama, Yoshitaka; Yoda, Koji; Watanabe, Toshihiro; Nimura-Matsune, Kaori; Mura, Kiyoshi; Tokue, Chiyoko; Katoh, Tetzuya; Kawasaki, Shinji; Niimura, Youichi

    2004-01-01

    Peroxiredoxin (Prx) constitutes a large family of enzymes found in microorganisms, animals, and plants, but the detection of the activities of Prx-linked hydroperoxide reductases (peroxiredoxin reductases) in cell extracts, and the purification based on peroxide reductase activity, have only been done in bacteria and Trypanosomatidae. A peroxiredoxin reductase (NADH oxidase) from a bacterium, Amphibacillus, displayed only poor activities in the presence of purified Prx from Saccharomyces or Synechocystis, while it is highly active in the presence of bacterial Prx. These results suggested that an enzyme system different from that in bacteria might exist for the reduction of Prx in yeast and cyanobacteria. Prx-linked hydroperoxide reductase activities were detected in cell extracts of Saccharomyces, Synechocystis, and Chlorella, and the enzyme activities of Saccharomyces and Chlorella were induced under vigorously aerated culture conditions and intensive light exposure conditions, respectively. Partial purification of Prx-linked peroxidase from the induced yeast cells indicated that the Prx-linked peroxidase system consists of two protein components, namely, thioredoxin and thioredoxin reductase. This finding is consistent with the previous report on its purification based on its protein protection activity against oxidation [Chae et al., J. Biol. Chem., 269, 27670-27678 (1994)]. In this study we have confirmed that Prx-linked peroxidase activity are widely distributed, not only in bacteria species and Trypanosomatidae, but also in yeast and photosynthetic microorganisms, and showed reconstitution of the activity from partially purified interspecies components.

  13. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  14. Carbodiimide induced cross-linking, ligand addition, and degradation in gelatin.

    PubMed

    Cammarata, Christopher R; Hughes, Mitchell E; Ofner, Clyde M

    2015-03-02

    The water-soluble carbodiimide, 1-ethyl-3-(3-(dimethylaminopropyl)-carbodiimide (EDC) is widely used in protein chemistry. We used EDC-induced gelatin cross-linking as a model for amide bond formation to resolve reaction ambiguities with common variables of buffers, gelatin concentration, and pH. Percentage changes in SEC high molecular weight peak areas were used to follow the reactions. Differences in reaction rate and extent were observed with four commonly used buffers, while differences in extent were observed for commonly used concentrations and pH. We also investigated an anhydride mechanism for aqueous EDC-induced amide bond formation that has received little attention since its proposal in 1995. Gelatin carboxyl groups had a synergistic role during the addition of hydrazine to corroborate the anhydride formation between carboxyl groups. EDC-induced degradation of gelatin was investigated using percentage changes in SEC low molecular weight peak areas. The degradation occurred in excess EDC at neutral to alkaline pH and was enhanced substantially when reacting amino groups were not available. A mechanism of EDC-induced gelatin degradation is proposed and designated the extended Khorana mechanism. This EDC side reaction has the potential to occur in peptides and proteins under similar conditions.

  15. A New Cross-Link for an Old Cross-Linking Drug: The Nitrogen Mustard Anticancer Agent Mechlorethamine Generates Cross-Links Derived from Abasic Sites in Addition to the Expected Drug-Bridged Cross-Links.

    PubMed

    Nejad, Maryam Imani; Johnson, Kevin M; Price, Nathan E; Gates, Kent S

    2016-12-20

    Nitrogen mustard anticancer drugs generate highly reactive aziridinium ions that alkylate DNA. Monoadducts arising from reaction with position N7 of guanine residues are the major DNA adducts generated by these agents. Interstrand cross-links in which the drug bridges position N7 of two guanine residues are formed in low yields relative to those of the monoadducts but are generally thought to be central to medicinal activity. The N7-alkylguanine residues generated by nitrogen mustards are depurinated to yield abasic (Ap) sites in duplex DNA. Here, we show that Ap sites generated by the nitrogen mustard mechlorethamine lead to interstrand cross-links of a type not previously associated with this drug. Gel electrophoretic data were consistent with early evolution of the expected drug-bridged cross-links, followed by the appearance of Ap-derived cross-links. The evidence is further consistent with a reaction pathway involving alkylation of a guanine residue in a 5'-GT sequence, followed by depurination to generate the Ap site, and cross-link formation via reaction of the Ap aldehyde residue with the opposing adenine residue at this site [Price, N. E., Johnson, K. M., Wang, J., Fekry, M. I., Wang, Y., and Gates, K. S. (2014) J. Am. Chem. Soc. 136, 3483-3490]. The monofunctional DNA-alkylating agents 2-chloro-N,N-diethylethanamine 5, (2-chloroethyl)ethylsulfide 6, and natural product leinamycin similarly were found to induce the formation of Ap-derived cross-links in duplex DNA. This work provides the first characterization of Ap-derived cross-links at sequences in which a cytosine residue is located directly opposing the Ap site. Cross-linking processes of this type could be relevant in medicine and biology because Ap sites with directly opposing cytosine residues occur frequently in genomic DNA via spontaneous or enzymatic depurination of guanine and N7-alkylguanine residues.

  16. Links among inflammation, sexual activity and ovulation

    PubMed Central

    Lorenz, Tierney K.; Worthman, Carol M.; Vitzthum, Virginia J.

    2015-01-01

    Background and objectives: We examined a mechanism that may coordinate trade-offs between reproduction and immune response in healthy women, namely, changes in inflammation across the ovarian cycle. Methodology: We investigated C-reactive protein (CRP), an inflammation marker, across two consecutive ovarian cycles in 61 Bolivian women. Participants provided saliva samples every other day, and dried blood spots on 5–6 days spread across weeks 2–3 of each cycle. Cycles were characterized as ovulatory/anovulatory based on profiles of reproductive hormones. Participants also reported whether they were sexually partnered with a male or sexually abstinent during the study. Results: High early-cycle, but not late-cycle, CRP was associated with anovulation. High inflammation at the end of one cycle was not associated with anovulation in the subsequent cycle. Among ovulatory cycles, women with sexual partners had significantly lower CRP at midcycle, and higher CRP at follicular and luteal phases; in contrast, sexually abstinent women had little cycle-related change in CRP. In anovulatory cycles, partnership had no effect on CRP. CRP varied significantly with socioeconomic status (higher in better-off than in poorer women). Conclusions and implications: These findings suggest that the cycle-specific effect of inflammation on ovarian function may be a flexible, adaptive mechanism for managing trade-offs between reproduction and immunity. Sociosexual behavior may moderate changes in inflammation across the ovarian cycle, suggesting that these shifts represent evolved mechanisms to manage the trade-offs between reproduction and immunity. Clinically, these findings support considering both menstrual cycle phase and sexual activity in evaluations of pre-menopausal women’s CRP concentrations. PMID:26675298

  17. Literature Links: Thematic Units Linking Read-Alouds and Computer Activities

    ERIC Educational Resources Information Center

    Labbo, Linda D.; Love, Mary Susan; Park Prior, Miri; Hubbard, Betty P.; Ryan, Tammy

    2006-01-01

    This book gives the reader ideas for providing primary-grade students with literacy learning opportunities that integrate conventional literacies, such as phonics and comprehension, with new literacies, such as multimedia composition and hyperlink navigation. The reader will find a variety of linked activities, including reading children's books,…

  18. The Cretaceous OAE1a-Submarine Plateau Link: Additional Geochemical Evidence from Marine Sedimentary Sections

    NASA Astrophysics Data System (ADS)

    Duncan, R. A.; Tiraboschi, D.; Erba, E.; Walczak, P.; Clarke, L. J.

    2007-12-01

    We explore the proposed link between submarine plateau volcanism associated with construction of the Ontong Java-Manihiki-Hikurangi plateau (122 Ma) and early Aptian Ocean Anoxic Event 1a (OAE1a) through biostratigraphic data and trace metal abundance anomalies in marine sedimentary sections recovered in cores from DSDP Site 167 (Magellan Rise), ODP Sites 463 and 866 (Mid-Pacific Mountains), and at the Cismon and Piobbico on-land drillsites (Belluno and Umbria-Marche Basins, Italy). Sections were correlated using bio- and magneto-stratigraphic data, and the global d13C isotope anomaly associated with OAE1a. Bulk sediment samples that bracket the OAE1a interval at each site were analyzed by ICP-MS methods. After normalizing element concentrations to Zr to remove the variable contribution of terrigenous material to these sediments, we detected an interval of concentrated metal abundance anomalies that precedes the abrupt positive climb in the d13C isotope excursion, beginning near magnetic chron M0, continuing through the organic-rich interval of anoxic conditions. The metal abundance anomalies (e.g., Sc, Cu, Co, Sn, Cr, Ni, V, Cd, Ag, Bi, Se, W, Mo, Sb, Pb up to 100x background), variable in intensity and pattern of elements, indicate that intermittent hydrothermal activity, in the form of both water/rock exchange and magmatic degassing, introduced large concentrations of trace metals into the Cretaceous ocean at the same time that turnover in plankton communities and increases in isotopically light organic carbon burial occurred. The stratigraphic position of the intervals of trace metal anomalies matches events prior, during and after OAE1a and indicates that intermittent hydrothermal activity on a massive scale triggered abrupt changes in biota, carbon burial and deep ocean oxygen contents. Calcareous nannofossil abundance and composition display major changes in biogenic paleofluxes, temperature and fertility of surface waters, coeval with metal enrichments

  19. Controlling self-sustained spiking activity by adding or removing one network link

    NASA Astrophysics Data System (ADS)

    Xu, Kesheng; Huang, Wenwen; Li, Baowen; Dhamala, Mukesh; Liu, Zonghua

    2013-06-01

    Being able to control the neuronal spiking activity in specific brain regions is central to a treatment scheme in several brain disorders such as epileptic seizures, mental depression, and Parkinson's diseases. Here, we present an approach for controlling self-sustained oscillations by adding or removing one directed network link in coupled neuronal oscillators, in contrast to previous approaches of adding stimuli or noise. We find that such networks can exhibit a variety of activity patterns such as on-off switch, sustained spikes, and short-term spikes. We derive the condition for a specific link to be the controller of the on-off effect. A qualitative analysis is provided to facilitate the understanding of the mechanism for spiking activity by adding one link. Our findings represent the first report on generating spike activity with the addition of only one directed link to a network and provide a deeper understanding of the microscopic roots of self-sustained spiking.

  20. [Kinetic analysis of additive effect on desulfurization activity].

    PubMed

    Han, Kui-hua; Zhao, Jian-li; Lu, Chun-mei; Wang, Yong-zheng; Zhao, Gai-ju; Cheng, Shi-qing

    2006-02-01

    The additive effects of A12O3, Fe2O3 and MnCO3 on CaO sulfation kinetics were investigated by thermogravimetic analysis method and modified grain model. The activation energy (Ea) and the pre-exponential factor (k0) of surface reaction, the activation energy (Ep) and the pre-exponential factor (D0) of product layer diffusion reaction were calculated according to the model. Additions of MnCO3 can enhance the initial reaction rate, product layer diffusion and the final CaO conversion of sorbents, the effect mechanism of which is similar to that of Fe2O3. The method based isokinetic temperature Ts and activation energy can not estimate the contribution of additive to the sulfation reactivity, the rate constant of the surface reaction (k), and the effective diffusivity of reactant in the product layer (Ds) under certain experimental conditions can reflect the effect of additives on the activation. Unstoichiometric metal oxide may catalyze the surface reaction and promote the diffusivity of reactant in the product layer by the crystal defect and distinct diffusion of cation and anion. According to the mechanism and effect of additive on the sulfation, the effective temperature and the stoichiometric relation of reaction, it is possible to improve the utilization of sorbent by compounding more additives to the calcium-based sorbent.

  1. Linking economic activities to the distribution of exotic plants.

    PubMed

    Taylor, Brad W; Irwin, Rebecca E

    2004-12-21

    The human enterprise is flooding Earth's ecosystems with exotic species. Human population size is often correlated with species introductions, whereas more proximate mechanisms, such as economic activities, are frequently overlooked. Here we present a hypothesis that links ecology and economics to provide a causal framework for the distribution of exotic plants in the United States. We test two competing hypotheses (the population-only and population-economic models) using a national data set of exotic plants, employing a statistical framework to simultaneously model direct and indirect effects of human population and ecological and economic variables. The population-only model included direct effects of human population and ecological factors as predictors of exotics. In contrast, the population-economic model included the direct effects of economic and ecological factors and the indirect effects of human population as predictors of exotics. The explicit addition of economic activity in the population-economic model provided a better explanation for the distribution of exotics than did the population-only model. The population-economic model explained 75% of the variation in the number of exotic plants in the 50 states and provided a good description of the observed number of exotic plants in the Canadian provinces and in other nations in 85% of the cases. A specific economic activity, real estate gross state product, had the strongest positive effect on the number of exotics. The strong influence of economics on exotics demonstrates that economics matter for resolving the exotic-species problem because the underlying causes, and some of the solutions, may lie in human-economic behaviors.

  2. Additivity, density fluctuations, and nonequilibrium thermodynamics for active Brownian particles

    NASA Astrophysics Data System (ADS)

    Chakraborti, Subhadip; Mishra, Shradha; Pradhan, Punyabrata

    2016-05-01

    Using an additivity property, we study particle-number fluctuations in a system of interacting self-propelled particles, called active Brownian particles (ABPs), which consists of repulsive disks with random self-propulsion velocities. From a fluctuation-response relation, a direct consequence of additivity, we formulate a thermodynamic theory which captures the previously observed features of nonequilibrium phase transition in the ABPs from a homogeneous fluid phase to an inhomogeneous phase of coexisting gas and liquid. We substantiate the predictions of additivity by analytically calculating the subsystem particle-number distributions in the homogeneous fluid phase away from criticality where analytically obtained distributions are compatible with simulations in the ABPs.

  3. Linking Plagioclase Zoning Patterns to Active Magma Processes

    NASA Astrophysics Data System (ADS)

    Izbekov, P. E.; Nicolaysen, K. P.; Neill, O. K.; Shcherbakov, V.; Plechov, P.; Eichelberger, J. C.

    2015-12-01

    Plagioclase, one of the most common and abundant mineral phases in volcanic products, will vary in composition in response to changes in temperature, pressure, composition of the ambient silicate melt, and melt H2O concentration. Changes in these parameters may cause dissolution or growth of plagioclase crystals, forming characteristic textural and compositional variations (zoning patterns), the complete core-to-rim sequence of which describes events experienced by an individual crystal from its nucleation to the last moments of its growth. Plagioclase crystals in a typical volcanic rock may look drastically dissimilar despite their spatial proximity and the fact that they have erupted together. Although they shared last moments of their growth during magma ascent and eruption, their prior experiences could be very different, as plagioclase crystals often come from different domains of the same magma system. Distinguishing similar zoning patterns, correlating them across the entire population of plagioclase crystals, and linking these patterns to specific perturbations in the magmatic system may provide additional perspective on the variety, extent, and timing of magma processes at active volcanic systems. Examples of magma processes, which may be distinguished based on plagioclase zoning patterns, include (1) cooling due to heat loss, (2) heating and/or pressure build up due to an input of new magmatic material, (3) pressure drop in response to magma system depressurization, and (4) crystal transfer between different magma domains/bodies. This review will include contrasting examples of zoning patters from recent eruptions of Karymsky, Bezymianny, and Tolbachik Volcanoes in Kamchatka, Augustine and Cleveland Volcanoes in Alaska, as well as from the drilling into an active magma body at Krafla, Iceland.

  4. Antiandrogenic activity of phthalate mixtures: Validity of concentration addition

    SciTech Connect

    Christen, Verena; Crettaz, Pierre; Oberli-Schrämmli, Aurelia; Fent, Karl

    2012-03-01

    Phthalates and bisphenol A have very widespread use leading to significant exposure of humans. They are suspected to interfere with the endocrine system, including the androgen, estrogen and the thyroid hormone system. Here we analyzed the antiandrogenic activity of six binary, and one ternary mixture of phthalates exhibiting complete antiandrogenic dose–response curves, and binary mixtures of phthalates and bisphenol A at equi-effective concentrations of EC{sub 10}, EC{sub 25} and EC{sub 50} in MDA-kb2 cells. Mixture activity followed the concentration addition (CA) model with a tendency to synergism at high and antagonism at low concentrations. Isoboles and the toxic unit approach (TUA) confirmed the additive to synergistic activity of the binary mixtures BBP + DBP, DBP + DEP and DEP + BPA at high concentrations. Both methods indicate a tendency to antagonism for the EC{sub 10} mixtures BBP + DBP, BBP + DEP and DBP + DEP, and the EC{sub 25} mixture of DBP + BPA. A ternary mixture revealed synergism at the EC{sub 50}, and weak antagonistic activity at the EC{sub 25} level by the TUA. A mixture of five phthalates representing a human urine composition and reflecting exposure to corresponding parent compounds showed no antiandrogenic activity. Our study demonstrates that CA is an appropriate concept to account for mixture effects of antiandrogenic phthalates and bisphenol A. The interaction indicates a departure from additivity to antagonism at low concentrations, probably due to interaction with the androgen receptor and/or cofactors. This study emphasizes that a risk assessment of phthalates should account for mixture effects by applying the CA concept. -- Highlights: ► Antiandrogenic activity of mixtures of 2 and 3 phthalates are assessed in MDA-kb2 cells. ► Mixture activities followed the concentration addition model. ► A tendency to synergism at high and antagonism at low levels occurred.

  5. Topological Constraints on Identifying Additive Link Metrics via End-to-end Paths Measurements

    DTIC Science & Technology

    2012-09-20

    U.K. Ministry of Defence or the U.K. Government. The U.S. and U.K. Governments are authorized to reproduce and distribute reprints for Government...MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION /AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES...with (partially) unknown probabil- ity distributions , and apply various parametric/nonparametric techniques to estimate the link metric distributions

  6. Cantaloupe melon peroxidase: characterization and effects of additives on activity.

    PubMed

    Lamikanra, O; Watson, M A

    2000-06-01

    Peroxidase in cantaloupe melon (Cucumis melo L. var. reticulatus Naud.), a fruit commonly fresh cut processed, was characterized to determine reaction pathway, optimal conditions for activity and effect of some additives on enzymatic action. Mn2+, CaCl2, NaNO2 and kinetin had partial inhibitory effects on enzyme activity. Activity was effectively inhibited by compounds capable of chelating peroxidase heme iron such as diethyldithiocarbamate and tiron, but unaffected by EDTA. Free radical scavenger, superoxide dismutase, also had no effect on reaction velocity. Enzymatic action was consistent with that of ascorbate peroxidase based on the relatively higher affinity for ascorbate over guaiacol. Optimum activity temperature was 50-55 degrees C. The enzyme was stable at temperatures below 40 degrees C and at 50 degrees C for up to 10 min. Over 90% of total activity was lost at 80 degrees C within 5 min. Broad pH optima, 5.5-7.5 at 50 degrees C and 6-7 at 30 degrees C, were obtained. Peroxidase activity in cantaloupe was higher than those in strawberry (Fragaria ananassa Duch.) and lettuce (Lactuca sativa L.), suggesting a relatively high oxidative stress in fresh cut cantaloupe. The potential use of ascorbate as an additive in fresh cut cantaloupe melon was demonstrated by its ability to preserve color in minimally processed fruits for 25 days at 4 degrees C, possibly as a result of an enhanced antioxidative action of the ascorbate-peroxidase complex and trace metal ion cofactors.

  7. Ecotoxicological effects of activated carbon addition to sediments.

    PubMed

    Jonker, Michiel T O; Suijkerbuijk, Martin P W; Schmitt, Heike; Sinnige, Theo L

    2009-08-01

    Activated carbon (AC) addition is a recently developed technique for the remediation of sediments and soils contaminated with hydrophobic organic chemicals. Laboratory and field experiments have demonstrated that the addition of 3-4% of AC can reduce aqueous concentrations and the bioaccumulation potential of contaminants. However, one aspect of the technique that has hardly received any attention is the possible occurrence of secondary, eco(toxico)logical effects, i.e., effects of AC addition on the health, behavior, and habitat quality of local organisms. In the present study, several ecotoxicological effects were investigated in AC-water and AC-enriched (0-25%) sediment systems. It was demonstrated that (i) powdered activated carbons can be toxic to aquatic invertebrates (Lumbriculus variegatus, Daphnia magna, and Corophium volutator) based on different mechanisms and preferably should be washed prior to application; (ii) Asellus aquaticus and Corophium volutator may physically avoid AC-enriched sediments; (iii) exposure of Lumbriculus variegatus to AC-enriched sediments lead to a time and dose-dependent reduction in the worms' lipid content, which was most probably caused by the observation that (iv) worm egestion rates decreased drastically upon AC addition, indicating that the presence of AC disturbed feeding behavior; and (v) there were no obvious effects on the microbiological community structure. All in all, these results suggest potential ecotoxicological effects of powdered AC addition and stress the need for a detailed further investigation of secondary effects of the technique, prior to any large-scale field application.

  8. The effect of an additional phosphite stabilizer on the properties of radiation cross-linked vitamin E blends of UHMWPE.

    PubMed

    Oral, Ebru; Neils, Andrew; Yabannavar, Pooja; Muratoglu, Orhun K

    2014-06-01

    Antioxidant stabilization of radiation cross-linked ultrahigh molecular weight polyethylene (UHMWPE) has been introduced to improve the oxidative stability of total joint implant bearing surfaces. Blending of an antioxidant with UHMWPE resin powder followed by consolidation and radiation cross-linking has been cleared by the FDA for use in both total hips and total knees for designs incorporating two antioxidants, namely vitamin E and Covernox™ (a medical grade version of Irganox™ 1010). The antioxidants in the polymer are expected to protect the polymer during consolidation, during radiation cross-linking, on the shelf before implantation, and in vivo after implantation. To maximize the protection of the polymer afforded by the antioxidant in vivo, a novel approach may be the use of multiple antioxidants, especially to protect the primary antioxidant for a longer period of time. We hypothesized that the addition of a phosphite stabilizer (Irgafos 168™) commonly used in conjunction with hindered phenolic antioxidants in polymer processing could improve the oxidative stability of radiation cross-linked blends of vitamin E. To test our hypothesis, we prepared UHMWPE blends with 0.05 wt% Irgafos and 0.05 wt% vitamin E and compared its cross-link density, wear resistance, tensile properties, and impact strength to control blends containing only vitamin E. Our hypothesis was not supported; the cross-link density of UHMWPE was significantly decreased by the additive without additional benefit to oxidative stability. To our knowledge, this was the first attempt at using multiple stabilizers in medical grade UHMWPE.

  9. Basophil activation test with food additives in chronic urticaria patients.

    PubMed

    Kang, Min-Gyu; Song, Woo-Jung; Park, Han-Ki; Lim, Kyung-Hwan; Kim, Su-Jung; Lee, Suh-Young; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Chang, Yoon-Seok

    2014-01-01

    The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU.

  10. Microplastic moves pollutants and additives to worms, reducing functions linked to health and biodiversity.

    PubMed

    Browne, Mark Anthony; Niven, Stewart J; Galloway, Tamara S; Rowland, Steve J; Thompson, Richard C

    2013-12-02

    Inadequate products, waste management, and policy are struggling to prevent plastic waste from infiltrating ecosystems [1, 2]. Disintegration into smaller pieces means that the abundance of micrometer-sized plastic (microplastic) in habitats has increased [3] and outnumbers larger debris [2, 4]. When ingested by animals, plastic provides a feasible pathway to transfer attached pollutants and additive chemicals into their tissues [5-15]. Despite positive correlations between concentrations of ingested plastic and pollutants in tissues of animals, few, if any, controlled experiments have examined whether ingested plastic transfers pollutants and additives to animals. We exposed lugworms (Arenicola marina) to sand with 5% microplastic that was presorbed with pollutants (nonylphenol and phenanthrene) and additive chemicals (Triclosan and PBDE-47). Microplastic transferred pollutants and additive chemicals into gut tissues of lugworms, causing some biological effects, although clean sand transferred larger concentrations of pollutants into their tissues. Uptake of nonylphenol from PVC or sand reduced the ability of coelomocytes to remove pathogenic bacteria by >60%. Uptake of Triclosan from PVC diminished the ability of worms to engineer sediments and caused mortality, each by >55%, while PVC alone made worms >30% more susceptible to oxidative stress. As global microplastic contamination accelerates, our findings indicate that large concentrations of microplastic and additives can harm ecophysiological functions performed by organisms.

  11. DNA cross-linking by intermediates in the mitomycin activation cascade

    SciTech Connect

    Cera, C.; Egbertson, M.; Teng, S.P.; Crothers, D.M.; Danishefsky, S.J. )

    1989-06-27

    The authors have assayed the cross-linking of oligonucleotides containing repeated mitomycin-reactive CpG sites in order to assess the factors that enhance activation of the carbamoyl function at C{sub 10}, yielding efficient mitomycin cross-linking. Drugs studied include mitomycin C (MC), N-methylmitomycin A (NMA), and the aziridinomitosene of NMA (MS). Drugs were reduced both by catalytic hydrogenation and by dithionite. They find that cross-linking by fully reduced NMA can be increased severalfold by addition of either excess dithionite reductant or the oxidant FeCl{sub 3}. Enhancement by FeCl{sub 3} is not seen with MC or MS, but excess dithionite increases cross-linking by all three compounds. They explain the action of Fe{sup 3+} by postulating production of the semiquinone of the monoadduct of mitomycin reacted at the C{sub 1}-position; according to this mechanism, departure of the carbamate from C{sub 10} is more efficient for the semiquinone than for the hydroquinone. However, the results imply that the hydroquinone can also function as a cross-linking agent. Excess dithionite beyond that required for stoichiometric reduction, activates the carbamate 2-3-fold for cross-linking. They find that the fully reduced leucoaziridinomitosene is highly unstable in solution, yet it produces efficient cross-linking. Hence, this compound is highly reactive in DNA alkylation and a good candidate for the role of primary alkylating agent.

  12. Non-parametric estimation of the odds ratios for continuous exposures using generalized additive models with an unknown link function.

    PubMed

    Cadarso-Suárez, Carmen; Roca-Pardiñas, Javier; Figueiras, Adolfo; González-Manteiga, Wenceslao

    2005-04-30

    The generalized additive, model (GAM) is a powerful and widely used tool that allows researchers to fit, non-parametrically, the effect of continuous predictors on a transformation of the mean response variable. Such a transformation is given by a so-called link function, and in GAMs this link function is assumed to be known. Nevertheless, if an incorrect choice is made for the link, the resulting GAM is misspecified and the results obtained may be misleading. In this paper, we propose a modified version of the local scoring algorithm that allows for the non-parametric estimation of the link function, by using local linear kernel smoothers. To better understand the effect that each covariate produces on the outcome, results are expressed in terms of the non-parametric odds ratio (OR) curves. Bootstrap techniques were used to correct the bias in the OR estimation and to construct point-wise confidence intervals. A simulation study was carried out to assess the behaviour of the resulting estimates. The proposed methodology was illustrated using data from the AIDS Register of Galicia (NW Spain), with a view to assessing the effect of the CD4 lymphocyte count on the probability of being AIDS-diagnosed via Tuberculosis (TB). This application shows how the link's flexibility makes it possible to obtain OR curve estimates that are less sensitive to the presence of outliers and unusual values that are often present in the extremes of the covariate distributions.

  13. Examining the Link Between Public Transit Use and Active Commuting

    PubMed Central

    Bopp, Melissa; Gayah, Vikash V.; Campbell, Matthew E.

    2015-01-01

    Background: An established relationship exists between public transportation (PT) use and physical activity. However, there is limited literature that examines the link between PT use and active commuting (AC) behavior. This study examines this link to determine if PT users commute more by active modes. Methods: A volunteer, convenience sample of adults (n = 748) completed an online survey about AC/PT patterns, demographic, psychosocial, community and environmental factors. t-test compared differences between PT riders and non-PT riders. Binary logistic regression analyses examined the effect of multiple factors on AC and a full logistic regression model was conducted to examine AC. Results: Non-PT riders (n = 596) reported less AC than PT riders. There were several significant relationships with AC for demographic, interpersonal, worksite, community and environmental factors when considering PT use. The logistic multivariate analysis for included age, number of children and perceived distance to work as negative predictors and PT use, feelings of bad weather and lack of on-street bike lanes as a barrier to AC, perceived behavioral control and spouse AC were positive predictors. Conclusions: This study revealed the complex relationship between AC and PT use. Further research should investigate how AC and public transit use are related. PMID:25898405

  14. Linking neuronal brain activity to the glucose metabolism

    PubMed Central

    2013-01-01

    Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. Methods First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Results Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. Conclusions The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported. PMID:23988084

  15. Cellular Links between Neuronal Activity and Energy Homeostasis

    PubMed Central

    Shetty, Pavan K.; Galeffi, Francesca; Turner, Dennis A.

    2012-01-01

    Neuronal activity, astrocytic responses to this activity, and energy homeostasis are linked together during baseline, conscious conditions, and short-term rapid activation (as occurs with sensory or motor function). Nervous system energy homeostasis also varies during long-term physiological conditions (i.e., development and aging) and with adaptation to pathological conditions, such as ischemia or low glucose. Neuronal activation requires increased metabolism (i.e., ATP generation) which leads initially to substrate depletion, induction of a variety of signals for enhanced astrocytic function, and increased local blood flow and substrate delivery. Energy generation (particularly in mitochondria) and use during ATP hydrolysis also lead to considerable heat generation. The local increases in blood flow noted following neuronal activation can both enhance local substrate delivery but also provides a heat sink to help cool the brain and removal of waste by-products. In this review we highlight the interactions between short-term neuronal activity and energy metabolism with an emphasis on signals and factors regulating astrocyte function and substrate supply. PMID:22470340

  16. Tools to investigate how interprofessional education activities link to competencies

    PubMed Central

    West, Courtney; Veronin, Michael; Landry, Karen; Kurz, Terri; Watzak, Bree; Quiram, Barbara; Graham, Lori

    2015-01-01

    Integrating interprofessional education (IPE) activities and curricular components in health professions education has been emphasized recently by the inclusion of accreditation standards across disciplines. The Interprofessional Education Collaborative (IPEC) established IPE competencies in 2009, but evaluating how activities link to competencies has not been investigated in depth. The purpose of this project is to investigate how well two IPE activities align with IPEC competencies. To evaluate how our IPE activities met IPEC competencies, we developed a checklist and an observation instrument. A brief description of each is included as well as the outcomes. We analyzed Disaster Day, a simulation exercise that includes participants from Nursing, Medicine, and Pharmacy, and Interprofessional Healthcare Ethics (IPHCE), a course that introduced medical, nursing, and pharmacy students to ethical issues using didactic sessions and case discussions. While both activities appeared to facilitate the development of IPE competencies, Disaster Day aligned more with IPEC competencies than the IPHCE course and appears to be a more comprehensive way of addressing IPEC competencies. However, offering one IPE activity or curricular element is not sufficient. Having several IPE options available, utilizing the tools we developed to map the IPE curriculum and evaluating competency coverage is recommended. PMID:26208707

  17. Overview of additive manufacturing activities at MTU aero engines

    NASA Astrophysics Data System (ADS)

    Bamberg, Joachim; Dusel, Karl-Heinz; Satzger, Wilhelm

    2015-03-01

    Additive Manufacturing (AM) is a promising technology to produce parts easily and effectively, just by using metallic powder or wire as starting material and a sophisticated melting process. In contrast to milling or turning technologies complex shaped and hollow parts can be built up in one step. That reduces the production costs and allows the implementation of complete new 3D designs. Therefore AM is also of great interest for aerospace and aero engine industry. MTU Aero Engines has focused its AM activities to the selective laser melting technique (SLM). This technique uses metallic powder and a laser for melting and building up the part layer by layer. It is shown which lead part was selected for AM and how the first production line was established. A special focus is set on the quality assurance of the selective laser melting process. In addition to standard non-destructive inspection techniques a new online monitoring tool was developed and integrated into the SLM machines. The basics of this technique is presented.

  18. Physical Activity and Snus: Is There a Link?

    PubMed Central

    Henninger, Stéphane; Fischer, Roland; Cornuz, Jacques; Studer, Joseph; Gmel, Gerhard

    2015-01-01

    The study aimed at assessing the link between physical activity (PA), sports activity and snus use among young men in Switzerland. Data from the Cohort Study on Substance Use Risk Factors (C-SURF) were used to measure PA with the International Physical Activity Questionnaire and sports activity with a single item. Multivariate logistic regression analysis was conducted to measure the association between snus use, PA and sports activity. Similar models were run for smoking and snuff use. Snus use increased in a dose-response association with PA (high level: OR = 1.72; 95% CI 1.16–2.55) and with individuals exercising once a week or more often (OR = 1.65; 95% CI 1.26–2.16; p < 0.001) or almost every day (OR = 2.27; 95% CI 1.72–3.01; p < 0.001) in separate models. Entered simultaneously, only sports and exercise maintained a basically unchanged significant dose-response relationship, whereas PA became non-significant. A non-significant dose-response relation was found for cigarette smoking and snuff use, indicating that the association with sport is specific to snus and not to tobacco use in general or smokeless tobacco in particular. This study showed that the association between snus use and sports is not specific to Nordic countries. PMID:26121189

  19. Physical Activity and Snus: Is There a Link?

    PubMed

    Henninger, Stéphane; Fischer, Roland; Cornuz, Jacques; Studer, Joseph; Gmel, Gerhard

    2015-06-25

    The study aimed at assessing the link between physical activity (PA), sports activity and snus use among young men in Switzerland. Data from the Cohort Study on Substance Use Risk Factors (C-SURF) were used to measure PA with the International Physical Activity Questionnaire and sports activity with a single item. Multivariate logistic regression analysis was conducted to measure the association between snus use, PA and sports activity. Similar models were run for smoking and snuff use. Snus use increased in a dose-response association with PA (high level: OR = 1.72; 95% CI 1.16-2.55) and with individuals exercising once a week or more often (OR = 1.65; 95% CI 1.26-2.16; p < 0.001) or almost every day (OR = 2.27; 95% CI 1.72-3.01; p < 0.001) in separate models. Entered simultaneously, only sports and exercise maintained a basically unchanged significant dose-response relationship, whereas PA became non-significant. A non-significant dose-response relation was found for cigarette smoking and snuff use, indicating that the association with sport is specific to snus and not to tobacco use in general or smokeless tobacco in particular. This study showed that the association between snus use and sports is not specific to Nordic countries.

  20. BAX channel activity mediates lysosomal disruption linked to Parkinson disease.

    PubMed

    Bové, Jordi; Martínez-Vicente, Marta; Dehay, Benjamin; Perier, Celine; Recasens, Ariadna; Bombrun, Agnes; Antonsson, Bruno; Vila, Miquel

    2014-05-01

    Lysosomal disruption is increasingly regarded as a major pathogenic event in Parkinson disease (PD). A reduced number of intraneuronal lysosomes, decreased levels of lysosomal-associated proteins and accumulation of undegraded autophagosomes (AP) are observed in PD-derived samples, including fibroblasts, induced pluripotent stem cell-derived dopaminergic neurons, and post-mortem brain tissue. Mechanistic studies in toxic and genetic rodent PD models attribute PD-related lysosomal breakdown to abnormal lysosomal membrane permeabilization (LMP). However, the molecular mechanisms underlying PD-linked LMP and subsequent lysosomal defects remain virtually unknown, thereby precluding their potential therapeutic targeting. Here we show that the pro-apoptotic protein BAX (BCL2-associated X protein), which permeabilizes mitochondrial membranes in PD models and is activated in PD patients, translocates and internalizes into lysosomal membranes early following treatment with the parkinsonian neurotoxin MPTP, both in vitro and in vivo, within a time-frame correlating with LMP, lysosomal disruption, and autophagosome accumulation and preceding mitochondrial permeabilization and dopaminergic neurodegeneration. Supporting a direct permeabilizing effect of BAX on lysosomal membranes, recombinant BAX is able to induce LMP in purified mouse brain lysosomes and the latter can be prevented by pharmacological blockade of BAX channel activity. Furthermore, pharmacological BAX channel inhibition is able to prevent LMP, restore lysosomal levels, reverse AP accumulation, and attenuate mitochondrial permeabilization and overall nigrostriatal degeneration caused by MPTP, both in vitro and in vivo. Overall, our results reveal that PD-linked lysosomal impairment relies on BAX-induced LMP, and point to small molecules able to block BAX channel activity as potentially beneficial to attenuate both lysosomal defects and neurodegeneration occurring in PD.

  1. Synthesis, Characterization, and Antibacterial Activity of Cross-Linked Chitosan-Glutaraldehyde

    PubMed Central

    Li, Bin; Shan, Chang-Lin; Zhou, Qing; Fang, Yuan; Wang, Yang-Li; Xu, Fei; Han, Li-Rong; Ibrahim, Muhammad; Guo, Long-Biao; Xie, Guan-Lin; Sun, Guo-Chang

    2013-01-01

    This present study deals with synthesis, characterization and antibacterial activity of cross-linked chitosan-glutaraldehyde. Results from this study indicated that cross-linked chitosan-glutaraldehyde markedly inhibited the growth of antibiotic-resistant Burkholderia cepacia complex regardless of bacterial species and incubation time while bacterial growth was unaffected by solid chitosan. Furthermore, high temperature treated cross-linked chitosan-glutaraldehyde showed strong antibacterial activity against the selected strain 0901 although the inhibitory effects varied with different temperatures. In addition, physical-chemical and structural characterization revealed that the cross-linking of chitosan with glutaraldehyde resulted in a rougher surface morphology, a characteristic Fourier transform infrared (FTIR) band at 1559 cm−1, a specific X-ray diffraction peak centered at 2θ = 15°, a lower contents of carbon, hydrogen and nitrogen, and a higher stability of glucose units compared to chitosan based on scanning electron microscopic observation, FTIR spectra, X-ray diffraction pattern, as well as elemental and thermo gravimetric analysis. Overall, this study indicated that cross-linked chitosan-glutaraldehyde is promising to be developed as a new antibacterial drug. PMID:23670533

  2. Neuroligin-1 links neuronal activity to sleep-wake regulation

    PubMed Central

    El Helou, Janine; Bélanger-Nelson, Erika; Freyburger, Marlène; Dorsaz, Stéphane; Curie, Thomas; La Spada, Francesco; Gaudreault, Pierre-Olivier; Beaumont, Éric; Pouliot, Philippe; Lesage, Frédéric; Frank, Marcos G.; Franken, Paul; Mongrain, Valérie

    2013-01-01

    Maintaining wakefulness is associated with a progressive increase in the need for sleep. This phenomenon has been linked to changes in synaptic function. The synaptic adhesion molecule Neuroligin-1 (NLG1) controls the activity and synaptic localization of N-methyl-d-aspartate receptors, which activity is impaired by prolonged wakefulness. We here highlight that this pathway may underlie both the adverse effects of sleep loss on cognition and the subsequent changes in cortical synchrony. We found that the expression of specific Nlg1 transcript variants is changed by sleep deprivation in three mouse strains. These observations were associated with strain-specific changes in synaptic NLG1 protein content. Importantly, we showed that Nlg1 knockout mice are not able to sustain wakefulness and spend more time in nonrapid eye movement sleep than wild-type mice. These changes occurred with modifications in waking quality as exemplified by low theta/alpha activity during wakefulness and poor preference for social novelty, as well as altered delta synchrony during sleep. Finally, we identified a transcriptional pathway that could underlie the sleep/wake-dependent changes in Nlg1 expression and that involves clock transcription factors. We thus suggest that NLG1 is an element that contributes to the coupling of neuronal activity to sleep/wake regulation. PMID:23716671

  3. Influence of nano-dispersive modified additive on cement activity

    SciTech Connect

    Sazonova, Natalya Badenikov, Artem Ivanova, Elizaveta; Skripnikova, Nelli

    2016-01-15

    In the work the influence of single-walled carbon nanotubes (SWCNT) on the cement activity and the processes of structure formation of the hardened cement paste in different periods of hydration are studied. The changes in the kinetic curves of the sample strength growth modified with SWCNT in amount of 0.01 and 0.0005 % are stipulated by the results of differential scanning colorimetry, scanning electronic and ionic microscopy, X-ray-phase analysis. It was found that the nano-modified additive may increase in the axis compressive strength of the system by 1.4–6.3 fold relatively to the reference samples and may reach 179.6 MPa. It may intensify the hydration process of calcium silicates as well as influence on the matrix of hardened cement paste. The studies are conducted on the structural changes in the hardened cement paste, the time periods of increase and decrease of the compressive strength of the samples, the amount of the calcium hydroxide and tobermorite-like gel as well as the degree of hydration C{sub 3}S and β-C{sub 2}S.

  4. Increasing the maximum achievable strain of a covalent polymer gel through the addition of mechanically invisible cross-links.

    PubMed

    Kean, Zachary S; Hawk, Jennifer L; Lin, Shaoting; Zhao, Xuanhe; Sijbesma, Rint P; Craig, Stephen L

    2014-09-10

    Hydrogels and organogels made from polymer networks are widely used in biomedical applications and soft, active devices for which the ability to sustain large deformations is required. The strain at which polymer networks fracture is typically improved through the addition of elements that dissipate energy, but these materials require extra work to achieve a given, desired level of deformation. Here, the addition of mechanically "invisible" supramolecular crosslinks causes substantial increases in the ultimate gel properties without incurring the added energetic costs of dissipation.

  5. Additional AIDoS women and environment activities.

    PubMed

    1992-07-01

    In addition to an information campaign on women and the environment, AIDoS has been involved in a range of activities and several conferences on the topic. The organization has implemented two microenterprises with a positive environmental impact and participated in the meetings on women and the environment leading up to the Global Forum held in Rio de Janeiro in June. AIDoS has also been invited to participate in the Interregional Workshop on the Role of Women in Environmentally Sound and Sustainable Development in Beijing in September 1992. In 1990, COCIS, FOCSIV, and CIPSI, the three confederations of Italian nongovernmental organizations (NGOs), signed a convention with the Ministry of Foreign Affairs to design and implement cooperative initiatives. AIDoS, a member of COCIS, presented two microprojects in India and Zaire which were subsequently financed. The implementation of these two projects opens a new area of involvement for AIDoS. The two projects are discussed. As part of its ongoing interest in women and the environment, AIDoS participated in two conferences in Miami in November 1991, Partners in Life, Global Assembly of Women, and the Environment and the World Congress of Women for a Healthy Planet, and in the Global Forum in Rio in June 1992. In September, AIDoS will participate in the Interregional Workshop on the Role of Women in Environmentally Sound and Sustainable Development organized by the UN Department of Economic and Social Affairs in collaboration with the UN International Research and Training Institute of the Advancement of Women.

  6. Activating additives for intensification of primary crude oil distillation

    SciTech Connect

    Saidakhmedov, I.M.; Syunyaev, Z.I.; Glagoleva, O.F.

    1987-03-01

    The proposed approach was tested by distilling an atmospheric resid from West Siberian crude in LPRN apparatus, following procedures given previously. The No, III lube cut from a commercial atmospheric-vacuum pipestill unit was added to the atmospheric resid. In order to evaluate the influence of the composition of the process additive on the vacuum distillation results, comparative tests were run on another type of additive differing substantially in hydrocarbon composition from the No. III lube cut - namely, the raffinate from the lube cut. The physicochemical characteristics of the atmospheric resid and the additives are listed.

  7. 42 CFR 460.140 - Additional quality assessment activities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... SERVICES (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) Quality Assessment and Performance Improvement § 460.140 Additional...

  8. 42 CFR 460.140 - Additional quality assessment activities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICES (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) Quality Assessment and Performance Improvement § 460.140 Additional...

  9. 42 CFR 460.140 - Additional quality assessment activities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SERVICES (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) Quality Assessment and Performance Improvement § 460.140 Additional...

  10. 42 CFR 460.140 - Additional quality assessment activities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... SERVICES (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) Quality Assessment and Performance Improvement § 460.140 Additional...

  11. Exosomes: The Link between GPCR Activation and Metastatic Potential?

    PubMed Central

    Isola, Allison L.; Chen, Suzie

    2016-01-01

    The activation of G-Protein Coupled Receptors (GPCRs) by their respective ligands initiates a cascade of multiple signaling processes within the cell, regulating growth, metabolism and other essential cellular functions. Dysregulation and aberrant expression of these GPCRs and their subsequent signaling cascades are associated with many different types of pathologies, including cancer. The main life threatening complication in patients diagnosed with cancer is the dissemination of cells from the primary tumor to distant vital organs within the body, metastasis. Communication between the primary tumor, immune system, and the site of future metastasis are some of the key events in the early stages of metastasis. It has been postulated that the communication is mediated by nanovesicles that, under non-pathological conditions, are released by normal cells to relay signals to other cells in the body. These nanovesicles are called exosomes, and are utilized by the tumor cell to influence changes within the recipient cell, such as bone marrow progenitor cells, and cells within the site of future metastatic growth, in order to prepare the site for colonization. Tumor cells have been shown to release an increased number of exosomes when compared to their normal cell counterpart. Exosome production and release are regulated by proteins involved in localization, degradation and size of the multivesicular body, whose function may be altered within cancer cells, resulting in the release of an increased number of these vesicles. This review investigates the possibility of GPCR signaling cascades acting as the upstream activator of proteins involved in exosome production and release, linking a commonly targeted trans-membrane protein class with cellular communication utilized by tumor cells in early stages of metastasis. PMID:27092178

  12. Sample data processing in an additive and reproducible taxonomic workflow by using character data persistently linked to preserved individual specimens

    PubMed Central

    Kilian, Norbert; Henning, Tilo; Plitzner, Patrick; Müller, Andreas; Güntsch, Anton; Stöver, Ben C.; Müller, Kai F.; Berendsohn, Walter G.; Borsch, Thomas

    2015-01-01

    We present the model and implementation of a workflow that blazes a trail in systematic biology for the re-usability of character data (data on any kind of characters of pheno- and genotypes of organisms) and their additivity from specimen to taxon level. We take into account that any taxon characterization is based on a limited set of sampled individuals and characters, and that consequently any new individual and any new character may affect the recognition of biological entities and/or the subsequent delimitation and characterization of a taxon. Taxon concepts thus frequently change during the knowledge generation process in systematic biology. Structured character data are therefore not only needed for the knowledge generation process but also for easily adapting characterizations of taxa. We aim to facilitate the construction and reproducibility of taxon characterizations from structured character data of changing sample sets by establishing a stable and unambiguous association between each sampled individual and the data processed from it. Our workflow implementation uses the European Distributed Institute of Taxonomy Platform, a comprehensive taxonomic data management and publication environment to: (i) establish a reproducible connection between sampled individuals and all samples derived from them; (ii) stably link sample-based character data with the metadata of the respective samples; (iii) record and store structured specimen-based character data in formats allowing data exchange; (iv) reversibly assign sample metadata and character datasets to taxa in an editable classification and display them and (v) organize data exchange via standard exchange formats and enable the link between the character datasets and samples in research collections, ensuring high visibility and instant re-usability of the data. The workflow implemented will contribute to organizing the interface between phylogenetic analysis and revisionary taxonomic or monographic work

  13. Dendrimer-Linked Antifreeze Proteins Have Superior Activity and Thermal Recovery.

    PubMed

    Stevens, Corey A; Drori, Ran; Zalis, Shiran; Braslavsky, Ido; Davies, Peter L

    2015-09-16

    By binding to ice, antifreeze proteins (AFPs) depress the freezing point of a solution and inhibit ice recrystallization if freezing does occur. Previous work showed that the activity of an AFP was incrementally increased by fusing it to another protein. Even larger increases in activity were achieved by doubling the number of ice-binding sites by dimerization. Here, we have combined the two strategies by linking multiple outward-facing AFPs to a dendrimer to significantly increase both the size of the molecule and the number of ice-binding sites. Using a heterobifunctional cross-linker, we attached between 6 and 11 type III AFPs to a second-generation polyamidoamine (G2-PAMAM) dendrimer with 16 reactive termini. This heterogeneous sample of dendrimer-linked type III constructs showed a greater than 4-fold increase in freezing point depression over that of monomeric type III AFP. This multimerized AFP was particularly effective at ice recrystallization inhibition activity, likely because it can simultaneously bind multiple ice surfaces. Additionally, attachment to the dendrimer has afforded the AFP superior recovery from heat denaturation. Linking AFPs together via polymers can generate novel reagents for controlling ice growth and recrystallization.

  14. Catechol-based matrix metalloproteinase inhibitors with additional antioxidative activity.

    PubMed

    Tauro, Marilena; Laghezza, Antonio; Loiodice, Fulvio; Piemontese, Luca; Caradonna, Alessia; Capelli, Davide; Montanari, Roberta; Pochetti, Giorgio; Di Pizio, Antonella; Agamennone, Mariangela; Campestre, Cristina; Tortorella, Paolo

    2016-01-01

    New catechol-containing chemical entities have been investigated as matrix metalloproteinase inhibitors as well as antioxidant molecules. The combination of the two properties could represent a useful feature due to the potential application in all the pathological processes characterized by increased proteolytic activity and radical oxygen species (ROS) production, such as inflammation and photoaging. A series of catechol-based molecules were synthesized and tested for both proteolytic and oxidative inhibitory activity, and the detailed binding mode was assessed by crystal structure determination of the complex between a catechol derivative and the matrix metalloproteinase-8. Surprisingly, X-ray structure reveals that the catechol oxygens do not coordinates the zinc atom.

  15. No link between the solar activity cycle and the diameter

    NASA Astrophysics Data System (ADS)

    Dame, L.; Cugnet, D.

    We do not understand the physical mechanisms responsible for the solar irradiance cycle. Measurements of small variations in the solar diameter could have been a critical probe of the Sun 's interior stratification, telling us how and where the solar luminosity is gated or stored. We have reanalyzed the 7 years of filtregrams data (150 000 photograms and magnetograms) of the SOHO/MDI experiment. We used the maximum possible sampling compatible with full frame recording, carefully avoiding any suspicious filtregram. Going further than the previous analysis of 2 years of data by Emilio et al. (Ap. J. 543,1007, 2000), we better corrected for changes in optical aberrations and, along Turmon et al. (Ap. J., 568, 396, 2002), we reduced radius measurement errors by identifying active regions and avoiding radius measurements herein. We found that, within the limit of our noise level uncertainties (2 mas), the solar diameter could be constant over the half cycle investigated. Our results confirm the recent reanalysis of the 7 years of MDI data made by Antia (Ap. J. 590, 567, 2003), with a completely different method since using the ultra-precise frequency variation of the f-modes (fundamental modes linked to the diameter). He found (carefully removing the yearly Earth induced variations and avoiding the SOHO data gap of 1999) that the diameter is constant over the half solar cycle (radius variation are less than 0.6 km, 0.8 mas - nothing over noise level). Along Antia, we can conclude that: "If a careful analysis is performed, then it turns out that there is no evidence for any variation in the solar radius." There were no theoretical reasons for large solar radius variations and there is no observational evidence for them with consistent space observations. If changes exit, they are to be very small.

  16. CNS Active O-Linked Glycopeptides that Penetrate the BBB

    NASA Astrophysics Data System (ADS)

    Jones, Evan; Polt, Robin

    2015-06-01

    Naturally occurring glycopeptides and glycoproteins play important roles in biological processes. Glycosylation is one of the most common post-translational modifications in vivo. Glycopeptides are involved in cell signaling and sorting, providing cell surface markers for recognition. From the drug design and synthesis perspective, modification of a peptide through glycosylation results in increased bioavailability and bioactivity of glycopeptides in living systems with negligible toxicity of degradation products. Glycopeptide synthesis can be accomplished through incorporation of a glycosylated amino acid in solid phase peptide synthesis (SPPS) to form the desired peptide, or via incorporation of sugar-amino acid moieties. Additionally, research indicates that glycosylation increases penetration of the blood-brain barrier (BBB) by peptides, which may lead to novel therapeutics for neurological disorders. Recent applications of glycopeptides have focused on the in vivo central nervous system effects after peripheral administration of centrally active peptides modified with various carbohydrates.

  17. Placebo-Activated Neural Systems are Linked to Antidepressant Responses

    PubMed Central

    Peciña, Marta; Bohnert, Amy S. B.; Sikora, Magdalena; Avery, Erich T.; Langenecker, Scott A.; Mickey, Brian J.; Zubieta, Jon-Kar

    2016-01-01

    Importance High placebo responses have been observed across a wide range of pathologies, severely impacting drug development. Objective Here we examined neurochemical mechanisms underlying the formation of placebo effects in patients with Major Depressive Disorder (MDD). Participants Thirty-five medication-free MDD patients. Design and Intervention We performed a single-blinded two-week cross-over randomized controlled trial of two identical oral placebos (described as having either “active” or “inactive” fast-acting antidepressant-like effects) followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor (SSRI) or in some cases, another agent as clinically indicated. The volunteers were studied with PET and the μ-opioid receptor (MOR)-selective radiotracer [11C]carfentanil after each 1-week “inactive” and “active” oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously (i.v.) within sight of the volunteer during PET scanning every 4 min over 20 min only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was utilized to test the individual capacity to acutely activate endogenous opioid neurotransmision under expectations of antidepressant effect. Setting A University Health System. Main Outcomes and Measures Changes in depressive symptoms in response to “active” placebo and antidepressant. Baseline and activation measures of MOR binding. Results Higher baseline MOR binding in the nucleus accumbens (NAc) was associated with better response to antidepressant treatment (r=0.48; p=0.02). Reductions in depressive symptoms after 1-week of “active” placebo treatment, compared to the “inactive”, were associated with increased placebo-induced μ-opioid neurotransmission in a network of regions implicated in emotion, stress regulation, and the

  18. Targeted gene addition in human CD34(+) hematopoietic cells for correction of X-linked chronic granulomatous disease.

    PubMed

    De Ravin, Suk See; Reik, Andreas; Liu, Pei-Qi; Li, Linhong; Wu, Xiaolin; Su, Ling; Raley, Castle; Theobald, Narda; Choi, Uimook; Song, Alexander H; Chan, Andy; Pearl, Jocelynn R; Paschon, David E; Lee, Janet; Newcombe, Hannah; Koontz, Sherry; Sweeney, Colin; Shivak, David A; Zarember, Kol A; Peshwa, Madhusudan V; Gregory, Philip D; Urnov, Fyodor D; Malech, Harry L

    2016-04-01

    Gene therapy with genetically modified human CD34(+) hematopoietic stem and progenitor cells (HSPCs) may be safer using targeted integration (TI) of transgenes into a genomic 'safe harbor' site rather than random viral integration. We demonstrate that temporally optimized delivery of zinc finger nuclease mRNA via electroporation and adeno-associated virus (AAV) 6 delivery of donor constructs in human HSPCs approaches clinically relevant levels of TI into the AAVS1 safe harbor locus. Up to 58% Venus(+) HSPCs with 6-16% human cell marking were observed following engraftment into mice. In HSPCs from patients with X-linked chronic granulomatous disease (X-CGD), caused by mutations in the gp91phox subunit of the NADPH oxidase, TI of a gp91phox transgene into AAVS1 resulted in ∼15% gp91phox expression and increased NADPH oxidase activity in ex vivo-derived neutrophils. In mice transplanted with corrected HSPCs, 4-11% of human cells in the bone marrow expressed gp91phox. This method for TI into AAVS1 may be broadly applicable to correction of other monogenic diseases.

  19. Hematite Surface Activation by Chemical Addition of Tin Oxide Layer.

    PubMed

    Carvalho, Waldemir M; Souza, Flavio L

    2016-09-05

    In this study, the effect of tin (Sn(4+) ) modification on the surface of hematite electrodes synthesized by an aqueous solution route at different times (2, 5, 10, 18, and 24 h) is investigated. As confirmed from X-ray diffraction results, the as-synthesized electrode exhibits an oxyhydroxide phase, which is converted into a pure hematite phase after being subjected to additional thermal treatment at 750 °C for 30 min. The tin-modified hematite electrode is prepared by depositing a solution of Sn(4+) precursor on the as-synthesized electrode, followed by thermal treatment under the same abovementioned conditions. This modification results in an enhancement of the photocurrent response for all hematite electrodes investigated and attains the highest values of around 1.62 and 2.3 mA cm(-2) at 1.23 and 1.4 V versus RHE, respectively, for electrodes obtained in short synthesis times (2 h). Contact angle measurements suggest that the deposition of Sn(4+) on the hematite electrode provides a more hydrophilic surface, which favors a chemical reaction at the interface between the electrode and electrolyte. This result generates new perspectives for understanding the deposition of Sn(4+) on the hematite electrode surface, which is in contrast with several studies previously reported; these studies state that the enhancement in photocurrent density is related to either the induction of an increased donor charge density or shift in the flat-band potential, which favors charge separation.

  20. Activation energy associated with the electromigration of oligosaccharides through viscosity modifier and polymeric additive containing background electrolytes.

    PubMed

    Kerékgyártó, Márta; Járvás, Gábor; Novák, Levente; Guttman, András

    2016-02-01

    The activation energy related to the electromigration of oligosaccharides can be determined from their measured electrophoretic mobilities at different temperatures. The effects of a viscosity modifier (ethylene glycol) and a polymeric additive (linear polyacrylamide) on the electrophoretic mobility of linear sugar oligomers with α1-4 linked glucose units (maltooligosaccharides) were studied in CE using the activation energy concept. The electrophoretic separations of 8-aminopyrene-1,3,6-trisulfonate-labeled maltooligosaccharides were monitored by LIF detection in the temperature range of 20-50°C, using either 0-60% ethylene glycol (viscosity modifier) or 0-3% linear polyacrylamide (polymeric additive) containing BGEs. Activation energy curves were constructed based on the slopes of the Arrhenius plots. With the use of linear polyacrylamide additive, solute size-dependent activation energy variations were found for the maltooligosaccharides with polymerization degrees below and above maltoheptaose (DP 7), probably due to molecular conformation changes and possible matrix interaction effects.

  1. Subseasonal forecast skill of the 1988 U.S. drought is linked to human activities (Invited)

    NASA Astrophysics Data System (ADS)

    Yamada, T.; Pokhrel, Y. N.; Yamahara, K.; Hanasaki, N.; Koirala, S.; Yeh, P. J.; Kanae, S.; Oki, T.

    2013-12-01

    Improving subseasonal hydrometeorological forecast skill for continental drought events to achieve stable water resources management and agricultural activities is a challenging task. The 1988 U.S. drought was one of the most severe extreme weather events in the U.S. followed by the 2012 U.S. drought. In this study, we perform several sets of ensemble forecast simulations starting on July 15 between 1986 and 1995 by using an Atmospheric General Circulation Model (AGCM), combined with several-human activity modules reflecting irrigation, domestic, industrial water demands associated with dam reservoir operation and groundwater pumping systems. Here, we find that the geographical distribution of subseasonal forecast skill for near surface hydrometeorological variables and precipitation over many regions in the Mississippi river basin is improved in the AGCM when these human activity modules are included in association with realistic land initializations. In addition, the use of the human activity modules contribute to decrease spreads for hydrometeorological variables among ensemble members in addition to smaller spread of surface soil moisture. This result suggests that keeping certain land surface wetness conditions for stable human activities is linking to decrease of freedom for atmospheric variables, and it could be called as the human induced land-atmosphere coupling.

  2. Happier People Live More Active Lives: Using Smartphones to Link Happiness and Physical Activity

    PubMed Central

    Lathia, Neal; Sandstrom, Gillian M.; Mascolo, Cecilia; Rentfrow, Peter J.

    2017-01-01

    Physical activity, both exercise and non-exercise, has far-reaching benefits to physical health. Although exercise has also been linked to psychological health (e.g., happiness), little research has examined physical activity more broadly, taking into account non-exercise activity as well as exercise. We examined the relationship between physical activity (measured broadly) and happiness using a smartphone application. This app has collected self-reports of happiness and physical activity from over ten thousand participants, while passively gathering information about physical activity from the accelerometers on users' phones. The findings reveal that individuals who are more physically active are happier. Further, individuals are happier in the moments when they are more physically active. These results emerged when assessing activity subjectively, via self-report, or objectively, via participants' smartphone accelerometers. Overall, this research suggests that not only exercise but also non-exercise physical activity is related to happiness. This research further demonstrates how smartphones can be used to collect large-scale data to examine psychological, behavioral, and health-related phenomena as they naturally occur in everyday life. PMID:28052069

  3. The Carbohydrate-linked Phosphorylcholine of the Parasitic Nematode Product ES-62 Modulates Complement Activation*

    PubMed Central

    Ahmed, Umul Kulthum; Maller, N. Claire; Iqbal, Asif J.; Al-Riyami, Lamyaa; Harnett, William; Raynes, John G.

    2016-01-01

    Parasitic nematodes manufacture various carbohydrate-linked phosphorylcholine (PCh)-containing molecules, including ES-62, a protein with an N-linked glycan terminally substituted with PCh. The PCh component is biologically important because it is required for immunomodulatory effects. We showed that most ES-62 was bound to a single protein, C-reactive protein (CRP), in normal human serum, displaying a calcium-dependent, high-avidity interaction and ability to form large complexes. Unexpectedly, CRP binding to ES-62 failed to efficiently activate complement as far as the C3 convertase stage in comparison with PCh-BSA and PCh-containing Streptococcus pneumoniae cell wall polysaccharide. C1q capture assays demonstrated an ES-62-CRP-C1q interaction in serum. The three ligands all activated C1 and generated C4b to similar extents. However, a C2a active site was not generated following ES-62 binding to CRP, demonstrating that C2 cleavage was far less efficient for ES-62-containing complexes. We proposed that failure of C2 cleavage was due to the flexible nature of carbohydrate-bound PCh and that reduced proximity of the C1 complex was the reason that C2 was poorly cleaved. This was confirmed using synthetic analogues that were similar to ES-62 only in respect of having a flexible PCh. Furthermore, ES-62 was shown to deplete early complement components, such as the rate-limiting C4, following CRP interaction and thereby inhibit classical pathway activation. Thus, flexible PCh-glycan represents a novel mechanism for subversion of complement activation. These data illustrate the importance of the rate-limiting C4/C2 stage of complement activation and reveal a new addition to the repertoire of ES-62 immunomodulatory mechanisms with possible therapeutic applications. PMID:27044740

  4. The Carbohydrate-linked Phosphorylcholine of the Parasitic Nematode Product ES-62 Modulates Complement Activation.

    PubMed

    Ahmed, Umul Kulthum; Maller, N Claire; Iqbal, Asif J; Al-Riyami, Lamyaa; Harnett, William; Raynes, John G

    2016-05-27

    Parasitic nematodes manufacture various carbohydrate-linked phosphorylcholine (PCh)-containing molecules, including ES-62, a protein with an N-linked glycan terminally substituted with PCh. The PCh component is biologically important because it is required for immunomodulatory effects. We showed that most ES-62 was bound to a single protein, C-reactive protein (CRP), in normal human serum, displaying a calcium-dependent, high-avidity interaction and ability to form large complexes. Unexpectedly, CRP binding to ES-62 failed to efficiently activate complement as far as the C3 convertase stage in comparison with PCh-BSA and PCh-containing Streptococcus pneumoniae cell wall polysaccharide. C1q capture assays demonstrated an ES-62-CRP-C1q interaction in serum. The three ligands all activated C1 and generated C4b to similar extents. However, a C2a active site was not generated following ES-62 binding to CRP, demonstrating that C2 cleavage was far less efficient for ES-62-containing complexes. We proposed that failure of C2 cleavage was due to the flexible nature of carbohydrate-bound PCh and that reduced proximity of the C1 complex was the reason that C2 was poorly cleaved. This was confirmed using synthetic analogues that were similar to ES-62 only in respect of having a flexible PCh. Furthermore, ES-62 was shown to deplete early complement components, such as the rate-limiting C4, following CRP interaction and thereby inhibit classical pathway activation. Thus, flexible PCh-glycan represents a novel mechanism for subversion of complement activation. These data illustrate the importance of the rate-limiting C4/C2 stage of complement activation and reveal a new addition to the repertoire of ES-62 immunomodulatory mechanisms with possible therapeutic applications.

  5. Activity-Dependent Adenosine Release May Be Linked to Activation of Na+-K+ ATPase: An In Vitro Rat Study

    PubMed Central

    Sims, Robert Edward; Dale, Nicholas

    2014-01-01

    In the brain, extracellular adenosine increases as a result of neuronal activity. The mechanisms by which this occurs are only incompletely understood. Here we investigate the hypothesis that the Na+ influxes associated with neuronal signalling activate the Na+-K+ ATPase which, by consuming ATP, generates intracellular adenosine that is then released via transporters. By measuring adenosine release directly with microelectrode biosensors, we have demonstrated that AMPA-receptor evoked adenosine release in basal forebrain and cortex depends on extracellular Na+. We have simultaneously imaged intracellular Na+ and measured adenosine release. The accumulation of intracellular Na+ during AMPA receptor activation preceded adenosine release by some 90 s. By removing extracellular Ca2+, and thus preventing indiscriminate neuronal activation, we used ouabain to test the role of the Na+-K+ ATPase in the release of adenosine. Under conditions which caused a Na+ influx, brief applications of ouabain increased the accumulation of intracellular Na+ but conversely rapidly reduced extracellular adenosine levels. In addition, ouabain greatly reduced the amount of adenosine released during application of AMPA. Our data therefore suggest that activity of the Na+-K+ ATPase is directly linked to the efflux of adenosine and could provide a universal mechanism that couples adenosine release to neuronal activity. The Na+-K+ ATPase-dependent adenosine efflux is likely to provide adenosine-mediated activity-dependent negative feedback that will be important in many diverse functional contexts including the regulation of sleep. PMID:24489921

  6. The ICAP Framework: Linking Cognitive Engagement to Active Learning Outcomes

    ERIC Educational Resources Information Center

    Chi, Michelene T. H.; Wylie, Ruth

    2014-01-01

    This article describes the ICAP framework that defines cognitive engagement activities on the basis of students' overt behaviors and proposes that engagement behaviors can be categorized and differentiated into one of four modes: "Interactive," "Constructive," "Active," and "Passive." The ICAP…

  7. Linking Language: Simple Language and Literacy Activities throughout the Curriculum.

    ERIC Educational Resources Information Center

    Rockwell, Robert; Hoge, Debra Reichert; Searcy, Bill

    This book provides practical, everyday activities to weave language development and early literacy activities into the daily schedule in an early childhood education program. The chapters are organized by areas common in most early childhood environments: (1) circle time; (2) snack time; (3) dramatic play; (4) outdoor play; (5) art; (6) sand and…

  8. Linking Employee Development Activity, Social Exchange and Organizational Citizenship Behavior

    ERIC Educational Resources Information Center

    Pierce, Heather R.; Maurer, Todd J.

    2009-01-01

    The authors examined "perceived beneficiary" of employee development (self, organization) for relationships with employee development activity. Perceived organizational support served as a moderator. The authors conclude that employees may engage in development activities to partly benefit their organization to the extent that a positive exchange…

  9. Adolescent Sexual Activity: Links between Relational Context and Depressive Symptoms

    ERIC Educational Resources Information Center

    Monahan, Kathryn C.; Lee, Joanna M.

    2008-01-01

    Little is known about the impact of the relational context of adolescent sexual activity on depressive symptoms. The present study examined trajectories of depressive symptoms among 6,602 adolescents (44% male, 60% White) taken from a nationally representative study (Add Health). Sexually active youth in romantic and casual relationships were…

  10. Active damping of oscillations in a long compliant manipulator link

    NASA Astrophysics Data System (ADS)

    Baker, C. P.; Evans, M. S.; Trudnowski, D. J.; Magee, D. P.

    1993-07-01

    A flexible manipulator test bed consisting of a fifteen foot long fixed-free compliant beam (representing a compliant manipulator link) with a Shilling Titan II dextrous manipulator mounted on its free end has been constructed at Pacific Northwest Laboratory (PNL). A comprehensive dynamic model which includes flexible body effects has been developed at PNL using a commercially available multibody dynamics code. A linearized version of the model is used to develop control strategies which use inertial forces generated by movements of the dextrous manipulator to damp out induced oscillations in the beam. These control strategies are tested on the model and shown to be feasible, and then implemented in the flexible manipulator testbed. Results from the hardware experiments are analyzed and compared with the model results.

  11. Lamellipodial actin mechanically links myosin activity with adhesion site formation

    PubMed Central

    Giannone, Gregory; Dubin-Thaler, Benjamin; Rossier, Olivier; Cai, Yunfei; Chaga, Oleg; Jiang, Guoying; Beaver, William; Döbereiner, Hans-Günther; Freund, Yoav; Borisy, Gary; Sheetz, Michael P.

    2013-01-01

    Summary Cell motility proceeds by cycles of edge protrusion, adhesion and retraction. Whether these functions are coordinated by biochemical or biomechanical processes is unknown. We find that myosin II pulls the rear of the lamellipodial actin network, causing upward bending, edge retraction and initiation of new adhesion sites. The network then separates from the edge and condenses over the myosin. Protrusion resumes as lamellipodial actin regenerates from the front and extends rearward until it reaches newly assembled myosin, initiating the next cycle. Upward bending, observed by evanescence and electron microscopy, results in ruffle formation when adhesion strength is low. Correlative fluorescence and electron microscopy shows that the regenerating lamellipodium forms a cohesive, separable layer of actin above the lamellum. Thus, actin polymerization periodically builds a mechanical link, the lamellipodium, connecting myosin motors with the initiation of adhesion sites, suggesting that the major functions driving motility are coordinated by a biomechanical process. PMID:17289574

  12. Linking online sexual activities to health outcomes among teens.

    PubMed

    O'Sullivan, Lucia F

    2014-01-01

    New digital technologies are highly responsive to many of the developmental needs of adolescents, including their need for intimate connection and social identity. This chapter explores adolescents' use of web-based sexual information, texting and "sexting," online dating sites, role-playing games, and sexually explicit media, and presents new data comparing the interpersonal and intrapersonal health outcomes among youth who engage in online sexual activities to those who do not. Despite the media-stoked concerns surrounding adolescents' participation in online sexual activities, the ubiquity of online activities and close overlap between online and offline activities indicate that this type of behavior should not be pathologized or used as a metric of problem behavior. The chapter concludes with implications for parents, educators, researchers, counselors, and health care providers, a call to challenge our deep discomfort around adolescent sexuality and to harness these technologies in ways that help promote growth and positive development.

  13. Biological spectra analysis: Linking biological activity profiles to molecular structure

    PubMed Central

    Fliri, Anton F.; Loging, William T.; Thadeio, Peter F.; Volkmann, Robert A.

    2005-01-01

    Establishing quantitative relationships between molecular structure and broad biological effects has been a longstanding challenge in science. Currently, no method exists for forecasting broad biological activity profiles of medicinal agents even within narrow boundaries of structurally similar molecules. Starting from the premise that biological activity results from the capacity of small organic molecules to modulate the activity of the proteome, we set out to investigate whether descriptor sets could be developed for measuring and quantifying this molecular property. Using a 1,567-compound database, we show that percent inhibition values, determined at single high drug concentration in a battery of in vitro assays representing a cross section of the proteome, provide precise molecular property descriptors that identify the structure of molecules. When broad biological activity of molecules is represented in spectra form, organic molecules can be sorted by quantifying differences between biological spectra. Unlike traditional structure–activity relationship methods, sorting of molecules by using biospectra comparisons does not require knowledge of a molecule's putative drug targets. To illustrate this finding, we selected as starting point the biological activity spectra of clotrimazole and tioconazole because their putative target, lanosterol demethylase (CYP51), was not included in the bioassay array. Spectra similarity obtained through profile similarity measurements and hierarchical clustering provided an unbiased means for establishing quantitative relationships between chemical structures and biological activity spectra. This methodology, which we have termed biological spectra analysis, provides the capability not only of sorting molecules on the basis of biospectra similarity but also of predicting simultaneous interactions of new molecules with multiple proteins. PMID:15625110

  14. Linking neural activity and molecular oscillations in the SCN

    PubMed Central

    Colwell, Christopher S.

    2015-01-01

    Neurons in the suprachiasmatic nucleus (SCN) function as part of a central timing circuit that drives daily changes in our behaviour and underlying physiology. A hallmark feature of SCN neuronal populations is that they are mostly electrically silent during the night, start to fire action potentials near dawn and then continue to generate action potentials with a slow and steady pace all day long. Sets of currents are responsible for this daily rhythm, with the strongest evidence for persistent Na+ currents, L-type Ca2+ currents, hyperpolarization-activated currents (IH), large-conductance Ca2+ activated K+ (BK) currents and fast delayed rectifier (FDR) K+ currents. These rhythms in electrical activity are crucial for the function of the circadian timing system, including the expression of clock genes, and decline with ageing and disease. This article reviews our current understanding of the ionic and molecular mechanisms that drive the rhythmic firing patterns in the SCN. PMID:21886186

  15. IKKα activation of NOTCH links tumorigenesis via FOXA2 suppression.

    PubMed

    Liu, Mo; Lee, Dung-Fang; Chen, Chun-Te; Yen, Chia-Jui; Li, Long-Yuan; Lee, Hong-Jen; Chang, Chun-Ju; Chang, Wei-Chao; Hsu, Jung-Mao; Kuo, Hsu-Ping; Xia, Weiya; Wei, Yongkun; Chiu, Pei-Chun; Chou, Chao-Kai; Du, Yi; Dhar, Debanjan; Karin, Michael; Chen, Chung-Hsuan; Hung, Mien-Chie

    2012-01-27

    Proinflammatory cytokine TNFα plays critical roles in promoting malignant cell proliferation, angiogenesis, and tumor metastasis in many cancers. However, the mechanism of TNFα-mediated tumor development remains unclear. Here, we show that IKKα, an important downstream kinase of TNFα, interacts with and phosphorylates FOXA2 at S107/S111, thereby suppressing FOXA2 transactivation activity and leading to decreased NUMB expression, and further activates the downstream NOTCH pathway and promotes cell proliferation and tumorigenesis. Moreover, we found that levels of IKKα, pFOXA2 (S107/111), and activated NOTCH1 were significantly higher in hepatocellular carcinoma tumors than in normal liver tissues and that pFOXA2 (S107/111) expression was positively correlated with IKKα and activated NOTCH1 expression in tumor tissues. Therefore, dysregulation of NUMB-mediated suppression of NOTCH1 by TNFα/IKKα-associated FOXA2 inhibition likely contributes to inflammation-mediated cancer pathogenesis. Here, we report a TNFα/IKKα/FOXA2/NUMB/NOTCH1 pathway that is critical for inflammation-mediated tumorigenesis and may provide a target for clinical intervention in human cancer.

  16. Linking Mission to Learning Activities for Assurance of Learning

    ERIC Educational Resources Information Center

    Yeung, Shirley Mo-ching

    2011-01-01

    Can accreditation-related requirements and mission statements measure learning outcomes? This study focuses on triangulating accreditation-related requirements with mission statements and learning activities to learning outcomes. This topic has not been comprehensively explored in the past. After looking into the requirements of AACSB, ISO, and…

  17. Linking estrogen receptor β expression with inflammatory bowel disease activity

    PubMed Central

    Pierdominici, Marina; Maselli, Angela; Varano, Barbara; Barbati, Cristiana; Cesaro, Paola; Spada, Cristiano; Zullo, Angelo; Lorenzetti, Roberto; Rosati, Marco; Rainaldi, Gabriella; Limiti, Maria Rosaria; Guidi, Luisa

    2015-01-01

    Crohn disease (CD) and ulcerative colitis (UC) are chronic forms of inflammatory bowel disease (IBD) whose pathogenesis is only poorly understood. Estrogens have a complex role in inflammation and growing evidence suggests that these hormones may impact IBD pathogenesis. Here, we demonstrated a significant reduction (p < 0.05) of estrogen receptor (ER)β expression in peripheral blood T lymphocytes from CD/UC patients with active disease (n = 27) as compared to those in remission (n = 21) and healthy controls (n = 29). Accordingly, in a subgroup of CD/UC patients undergoing to anti-TNF-α therapy and responsive to treatment, ERβ expression was higher (p < 0.01) than that observed in not responsive patients and comparable to that of control subjects. Notably, ERβ expression was markedly decreased in colonic mucosa of CD/UC patients with active disease, reflecting the alterations observed in peripheral blood T cells. ERβ expression inversely correlated with interleukin (IL)-6 serum levels and exogenous exposure of both T lymphocytes and intestinal epithelial cells to this cytokine resulted in ERβ downregulation. These results demonstrate that the ER profile is altered in active IBD patients at both mucosal and systemic levels, at least in part due to IL-6 dysregulation, and highlight the potential exploitation of T cell-associated ERβ as a biomarker of endoscopic disease activity. PMID:26497217

  18. Linking Aerosol Source Activities to Present and Future Climate Effects

    NASA Astrophysics Data System (ADS)

    Koch, D.; Bond, T. C.; Streets, D.; Menon, S.; Unger, N.

    2007-05-01

    Aerosol source sectors (transport, power, industry, residential, biomass burning) generate distinct mixtures of aerosol species. These mixtures in turn have different effects on climate. As sectoral emissions change in coming decades, whether by regulation or not, it is helpful to link pollution from source types to climate consequences. We do so, using our global (GISS GCM) aerosol model for present and future IPCC SRES scenarios. According to our model, residential and transport sectors have net positive 1995 aerosol forcings (0.04 and 0.03 W m-2) due to their large black carbon contents. However, the sulfate-dominated power and industry sectors have net negative 1995 forcings (-0.10 and -0.09 W m-2). Due to the near-balance of absorbing and scattering components, biomass burning forcing is small. For the 2050 SRES A1B scenario, the net (negative) aerosol forcing is double 1995 due primarily to increased sulfur emissions in the industry and power sectors. For 2050 B1 the net (negative) forcing decreases relative to 1995, as sulfur emissions are reduced. Both future scenarios project decreasing residential emissions. Yet transport emissions are expected to remain significant and thus become the dominant source of warming aerosols in the future. Aerosol pollution is projected to shift southward relative to the present, as the current industrialized regions generally reduce emissions and tropical and southern hemispheric regions continue to develop. Similar to these SRES scenarios, IIASA scenarios project a decline in residential emissions; however IIASA is more optimistic about transport sector emissions reductions. We will conduct present-day climate experiments, including aerosol direct and indirect effects, to study impacts of power and transport sectors on climate features such as air temperature and hydrologic cycle.

  19. Hypoglycemic activity of dried extracts of Bauhinia forficata Link.

    PubMed

    da Cunha, A M; Menon, S; Menon, R; Couto, A G; Bürger, C; Biavatti, M W

    2010-01-01

    Leaves of the pantropical genus Bauhinia (Fabaceae) are known popularly as cow's foot, due to their unique characteristic bilobed aspect. The species Bauhinia forficata (Brazilian Orchid-tree) is widely used in folk medicine as an antidiabetic. The present work investigates the hypoglycemic activity of the dried extracts of Bauhinia forficata leaves in vivo, as well as the influence of the drying and granulation processes on this activity. The fluid extract was dried to generate oven-dried (ODE), spray-dried (SDE) and wet granulation (WGE) extracts, with the aid of colloidal silicon dioxide and/or cellulose:lactose mixture. The dried extracts were characterized by spectrophotometric, chromatographic and photo microscopy image analysis. 200 mg/kg body wt., p.o. of each dried product were administered orally to male Wistar rats over 7 days old, for biomonitoring of the hypoglycemic activity profile. The effect of the extracts was studied in STZ-induced diabetic rats. After 7 days of treatment, fasting glucose was determined, and the livers were removed, dried on tissue paper, weighed, and stored at -20 degrees C to estimate hepatic glycogen. Our results show that spray-drying or oven-drying processes applied to B. forficata extracts did not significantly alter its flavonoid profile or its hypoglycemic activity. Indeed, the dried extracts of B. forficata act differently from glibenclamide. Despite the lower active content in WGE, because of the higher concentration of adjuvants, the use of the granulation process improved the manufacturing properties of the ODE, making this material more appropriate for use in tablets or capsules.

  20. K63-Linked Ubiquitination in Kinase Activation and Cancer

    PubMed Central

    Wang, Guocan; Gao, Yuan; Li, Liren; Jin, Guoxiang; Cai, Zhen; Chao, Jui-I; Lin, Hui-Kuan

    2012-01-01

    Ubiquitination has been demonstrated to play a pivotal role in multiple biological functions, which include cell growth, proliferation, apoptosis, DNA damage response, innate immune response, and neuronal degeneration. Although the role of ubiquitination in targeting proteins for proteasome-dependent degradation have been extensively studied and well-characterized, the critical non-proteolytic functions of ubiquitination, such as protein trafficking and kinase activation, involved in cell survival and cancer development, just start to emerge, In this review, we will summarize recent progresses in elucidating the non-proteolytic function of ubiquitination signaling in protein kinase activation and its implications in human cancers. The advancement in the understanding of the novel functions of ubiquitination in signal transduction pathways downstream of growth factor receptors may provide novel paradigms for the treatment of human cancers. PMID:22649774

  1. The link between tidal interaction and nuclear activity in galaxies

    NASA Technical Reports Server (NTRS)

    Lin, D. N. C.; Pringle, J. E.; Rees, M. J.

    1988-01-01

    It is considered how nuclear activity in galaxies may be induced by the tidal perturbation of companion galaxies. It is suggested that if the central regions of the galaxies contain marginally self-gravitating disks of gas, trailing spiral density waves, triggered by nonaxisymmetric gravitational instability, lead to efficient angular momentum transport. If the net effect of the external perturbation is to increase the effect of self-gravity in the gas, then the result is to induce a considerable increase in the mass accretion rate into the central region on a relatively short time scale. With a simple prescription, the evolution of self-gravitating accretion disks is examined in this context. These results are discussed in the context of the frequent occurrence of nuclear activity in interacting galaxies.

  2. Pyrophosphate-condensing activity linked to nucleic acid synthesis.

    PubMed Central

    Volloch, V Z; Rits, S; Tumerman, L

    1979-01-01

    In some preparations of DNA dependent RNA polymerase a new enzymatic activity has been found which catalyzes the condensation of two pyrophosphate molecules, liberated in the process of RNA synthesis, to one molecule of orthophosphate and one molecule of Mg (or Mn) - chelate complex with trimetaphosphate. This activity can also cooperate with DNA-polymerase, on condition that both enzymes originate from the same cells. These results point to two general conclusions. First, energy is conserved in the overall process of nucleic acid synthesis and turnover, so that the process does not require an energy influx from the cell's general resources. Second, the synthesis of nucleic acids is catalyzed by a complex enzyme system which contains at least two separate enzymes, one responsible for nucleic acid polymerization and the other for energy conservation via pyrophosphate condensation. Images PMID:88040

  3. Disulfide cross-linking influences symbiotic activities of nodule peptide NCR247.

    PubMed

    Shabab, Mohammed; Arnold, Markus F F; Penterman, Jon; Wommack, Andrew J; Bocker, Hartmut T; Price, Paul A; Griffitts, Joel S; Nolan, Elizabeth M; Walker, Graham C

    2016-09-06

    Interactions of rhizobia with legumes establish the chronic intracellular infection that underlies symbiosis. Within nodules of inverted repeat-lacking clade (IRLC) legumes, rhizobia differentiate into nitrogen-fixing bacteroids. This terminal differentiation is driven by host nodule-specific cysteine-rich (NCR) peptides that orchestrate the adaptation of free-living bacteria into intracellular residents. Medicago truncatula encodes a family of >700 NCR peptides that have conserved cysteine motifs. NCR247 is a cationic peptide with four cysteines that can form two intramolecular disulfide bonds in the oxidized forms. This peptide affects Sinorhizobium meliloti transcription, translation, and cell division at low concentrations and is antimicrobial at higher concentrations. By preparing the three possible disulfide-cross-linked NCR247 regioisomers, the reduced peptide, and a variant lacking cysteines, we performed a systematic study of the effects of intramolecular disulfide cross-linking and cysteines on the activities of an NCR peptide. The relative activities of the five NCR247 variants differed strikingly among the various bioassays, suggesting that the NCR peptide-based language used by plants to control the development of their bacterial partners during symbiosis is even greater than previously recognized. These patterns indicate that certain NCR bioactivities require cysteines whereas others do not. The results also suggest that NCR247 may exert some of its effects within the cell envelope whereas other activities occur in the cytoplasm. BacA, a membrane protein that is critical for symbiosis, provides protection against all bactericidal forms of NCR247. Oxidative folding protects NCR247 from degradation by the symbiotically relevant metalloprotease HrrP (host range restriction peptidase), suggesting that disulfide bond formation may additionally stabilize NCR peptides during symbiosis.

  4. Disulfide cross-linking influences symbiotic activities of nodule peptide NCR247

    PubMed Central

    Shabab, Mohammed; Arnold, Markus F. F.; Penterman, Jon; Wommack, Andrew J.; Bocker, Hartmut T.; Price, Paul A.; Griffitts, Joel S.; Nolan, Elizabeth M.; Walker, Graham C.

    2016-01-01

    Interactions of rhizobia with legumes establish the chronic intracellular infection that underlies symbiosis. Within nodules of inverted repeat-lacking clade (IRLC) legumes, rhizobia differentiate into nitrogen-fixing bacteroids. This terminal differentiation is driven by host nodule-specific cysteine-rich (NCR) peptides that orchestrate the adaptation of free-living bacteria into intracellular residents. Medicago truncatula encodes a family of >700 NCR peptides that have conserved cysteine motifs. NCR247 is a cationic peptide with four cysteines that can form two intramolecular disulfide bonds in the oxidized forms. This peptide affects Sinorhizobium meliloti transcription, translation, and cell division at low concentrations and is antimicrobial at higher concentrations. By preparing the three possible disulfide–cross-linked NCR247 regioisomers, the reduced peptide, and a variant lacking cysteines, we performed a systematic study of the effects of intramolecular disulfide cross-linking and cysteines on the activities of an NCR peptide. The relative activities of the five NCR247 variants differed strikingly among the various bioassays, suggesting that the NCR peptide-based language used by plants to control the development of their bacterial partners during symbiosis is even greater than previously recognized. These patterns indicate that certain NCR bioactivities require cysteines whereas others do not. The results also suggest that NCR247 may exert some of its effects within the cell envelope whereas other activities occur in the cytoplasm. BacA, a membrane protein that is critical for symbiosis, provides protection against all bactericidal forms of NCR247. Oxidative folding protects NCR247 from degradation by the symbiotically relevant metalloprotease HrrP (host range restriction peptidase), suggesting that disulfide bond formation may additionally stabilize NCR peptides during symbiosis. PMID:27551097

  5. Timeless links replication termination to mitotic kinase activation.

    PubMed

    Dheekollu, Jayaraju; Wiedmer, Andreas; Hayden, James; Speicher, David; Gotter, Anthony L; Yen, Tim; Lieberman, Paul M

    2011-05-06

    The mechanisms that coordinate the termination of DNA replication with progression through mitosis are not completely understood. The human Timeless protein (Tim) associates with S phase replication checkpoint proteins Claspin and Tipin, and plays an important role in maintaining replication fork stability at physical barriers, like centromeres, telomeres and ribosomal DNA repeats, as well as at termination sites. We show here that human Tim can be isolated in a complex with mitotic entry kinases CDK1, Auroras A and B, and Polo-like kinase (Plk1). Plk1 bound Tim directly and colocalized with Tim at a subset of mitotic structures in M phase. Tim depletion caused multiple mitotic defects, including the loss of sister-chromatid cohesion, loss of mitotic spindle architecture, and a failure to exit mitosis. Tim depletion caused a delay in mitotic kinase activity in vivo and in vitro, as well as a reduction in global histone H3 S10 phosphorylation during G2/M phase. Tim was also required for the recruitment of Plk1 to centromeric DNA and formation of catenated DNA structures at human centromere alpha satellite repeats. Taken together, these findings suggest that Tim coordinates mitotic kinase activation with termination of DNA replication.

  6. Candidates, Campaigns, & Elections: Projects, Activities, Literature Links. Grades 4-8.

    ERIC Educational Resources Information Center

    Scher, Linda; Johnson, Mary Oates

    This resource book provides activities about elections and campaigns that involve students in active learning. The book introduces students to the organization of government and how politicians present themselves and are covered by the media. The activities include literature links, primary sources, and maps and charts for tracking results. The…

  7. Linking petrology and seismology at an active volcano.

    PubMed

    Saunders, Kate; Blundy, Jon; Dohmen, Ralf; Cashman, Kathy

    2012-05-25

    Many active volcanoes exhibit changes in seismicity, ground deformation, and gas emissions, which in some instances arise from magma movement in the crust before eruption. An enduring challenge in volcano monitoring is interpreting signs of unrest in terms of the causal subterranean magmatic processes. We examined over 300 zoned orthopyroxene crystals from the 1980-1986 eruption of Mount St. Helens that record pulsatory intrusions of new magma and volatiles into an existing larger reservoir before the eruption occurred. Diffusion chronometry applied to orthopyroxene crystal rims shows that episodes of magma intrusion correlate temporally with recorded seismicity, providing evidence that some seismic events are related to magma intrusion. These time scales are commensurate with monitoring signals at restless volcanoes, thus improving our ability to forecast volcanic eruptions by using petrology.

  8. Radical-scavenging-linked antioxidant activities of extracts from black chokeberry and blueberry cultivated in Korea.

    PubMed

    Hwang, Seok Joon; Yoon, Won Byong; Lee, Ok-Hwan; Cha, Seung Ju; Kim, Jong Dai

    2014-03-01

    The objective of this study was to investigate the radical-scavenging-linked antioxidant properties of the extracts from black chokeberry and blueberry cultivated in Korea. The 70% ethanol extracts were prepared from black chokeberry and blueberry, and evaluated for total phenolic content, total flavonoid content, total proanthocyanidin content, and antioxidative activities, using various in vitro assays, such as DPPH(2,2-diphenyl-1-picrylhydrazyl), ABTS(2,2-azino-bis-(3-ethylenebenzothiozoline-6-sulphonic acid)) radical-scavenging activity, FRAP(ferric-reducing antioxidant power) and reducing power. The major phenolic compounds, including cyanidin-3-galactoside, cyanidin-3-arabinoside, neochlorogenic acid, procyanidin B1, were analysed by HPLC with a photodiode array detector. Results showed that total phenol, flavonoid and proanthocyanidin contents of black chokeberry extract were higher than those of blueberry extract. In addition, black chokeberry extract exhibited higher free radical-scavenging activity and reducing power than did blueberry extract. Cyanidin-3-galactoside was identified as a major phenolic compound, with considerable content in black chokeberry, that correlated with its higher antioxidant and radical-scavenging effects. These results suggest that black chokeberry extracts could be considered as a good source of natural antioxidants and functional food ingredients.

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

    PubMed

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

    2015-12-01

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

  10. Centennial Scale Variations in Lake Productivity Linked to Solar Activity

    NASA Astrophysics Data System (ADS)

    Englebrecht, A.; Bhattacharyya, S.; Guilderson, T. P.; Ingram, L.; Byrne, R.

    2012-12-01

    Solar variations on both decadal and centennial timescales have been associated with climate phenomena (van Loon et al., 2004; Hodell et al., 2001; White et al., 1997). The energy received by the Earth at the peak of the solar cycle increases by <0.1%; so the question has remained of how this could be amplified to produce an observable climate response. Recent modeling shows that the response of the Earth's climate system to the 11-year solar cycle may be amplified through stratosphere and ocean feedbacks and has the potential to impact climate variability on a multidecadal to centennial timescales (Meehl et al., 2009). Here, we report a 1000-year record of changes in the stratigraphy and carbon isotope composition of varved lake sediment from Isla Isabela (22°N, 106°W) in the subtropical northeast Pacific. Stable carbon isotopes and carbonate stratigraphy can be used to infer surface productivity in the lake. Our analysis shows variations in primary productivity on centennial timescales and suggests that solar activity may be an important component of Pacific climate variability. A possible response during solar maxima acts to keep the eastern equatorial Pacific cooler and drier than usual, producing conditions similar to a La Niña event. In the region around Isla Isabela peak solar years were characterized by decreased surface temperatures and suppressed precipitation (Meehl et al., 2009), which enhance productivity at Isabela (Kienel et al. 2011). In the future, we plan to analyze the data using advanced time series analysis techniques like the wavelets together with techniques to handle irregularly spaced time series data. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. LLNL-ABS-571672

  11. Different dynamic resting state fMRI patterns are linked to different frequencies of neural activity.

    PubMed

    Thompson, Garth John; Pan, Wen-Ju; Keilholz, Shella Dawn

    2015-07-01

    Resting state functional magnetic resonance imaging (rsfMRI) results have indicated that network mapping can contribute to understanding behavior and disease, but it has been difficult to translate the maps created with rsfMRI to neuroelectrical states in the brain. Recently, dynamic analyses have revealed multiple patterns in the rsfMRI signal that are strongly associated with particular bands of neural activity. To further investigate these findings, simultaneously recorded invasive electrophysiology and rsfMRI from rats were used to examine two types of electrical activity (directly measured low-frequency/infraslow activity and band-limited power of higher frequencies) and two types of dynamic rsfMRI (quasi-periodic patterns or QPP, and sliding window correlation or SWC). The relationship between neural activity and dynamic rsfMRI was tested under three anesthetic states in rats: dexmedetomidine and high and low doses of isoflurane. Under dexmedetomidine, the lightest anesthetic, infraslow electrophysiology correlated with QPP but not SWC, whereas band-limited power in higher frequencies correlated with SWC but not QPP. Results were similar under isoflurane; however, the QPP was also correlated to band-limited power, possibly due to the burst-suppression state induced by the anesthetic agent. The results provide additional support for the hypothesis that the two types of dynamic rsfMRI are linked to different frequencies of neural activity, but isoflurane anesthesia may make this relationship more complicated. Understanding which neural frequency bands appear as particular dynamic patterns in rsfMRI may ultimately help isolate components of the rsfMRI signal that are of interest to disorders such as schizophrenia and attention deficit disorder.

  12. Different dynamic resting state fMRI patterns are linked to different frequencies of neural activity

    PubMed Central

    Thompson, Garth John; Pan, Wen-Ju

    2015-01-01

    Resting state functional magnetic resonance imaging (rsfMRI) results have indicated that network mapping can contribute to understanding behavior and disease, but it has been difficult to translate the maps created with rsfMRI to neuroelectrical states in the brain. Recently, dynamic analyses have revealed multiple patterns in the rsfMRI signal that are strongly associated with particular bands of neural activity. To further investigate these findings, simultaneously recorded invasive electrophysiology and rsfMRI from rats were used to examine two types of electrical activity (directly measured low-frequency/infraslow activity and band-limited power of higher frequencies) and two types of dynamic rsfMRI (quasi-periodic patterns or QPP, and sliding window correlation or SWC). The relationship between neural activity and dynamic rsfMRI was tested under three anesthetic states in rats: dexmedetomidine and high and low doses of isoflurane. Under dexmedetomidine, the lightest anesthetic, infraslow electrophysiology correlated with QPP but not SWC, whereas band-limited power in higher frequencies correlated with SWC but not QPP. Results were similar under isoflurane; however, the QPP was also correlated to band-limited power, possibly due to the burst-suppression state induced by the anesthetic agent. The results provide additional support for the hypothesis that the two types of dynamic rsfMRI are linked to different frequencies of neural activity, but isoflurane anesthesia may make this relationship more complicated. Understanding which neural frequency bands appear as particular dynamic patterns in rsfMRI may ultimately help isolate components of the rsfMRI signal that are of interest to disorders such as schizophrenia and attention deficit disorder. PMID:26041826

  13. Investigation of cross-linked and additive containing polymer materials for membranes with improved performance in pervaporation and gas separation.

    PubMed

    Hunger, Katharina; Schmeling, Nadine; Jeazet, Harold B Tanh; Janiak, Christoph; Staudt, Claudia; Kleinermanns, Karl

    2012-10-22

    Pervaporation and gas separation performances of polymer membranes can be improved by crosslinking or addition of metal-organic frameworks (MOFs). Crosslinked copolyimide membranes show higher plasticization resistance and no significant loss in selectivity compared to non-crosslinked membranes when exposed to mixtures of CO2/CH4 or toluene/cyclohexane. Covalently crosslinked membranes reveal better separation performances than ionically crosslinked systems. Covalent interlacing with 3-hydroxypropyldimethylmaleimide as photocrosslinker can be investigated in situ in solution as well as in films, using transient UV/Vis and FTIR spectroscopy. The photocrosslinking yield can be determined from the FTIR-spectra. It is restricted by the stiffness of the copolyimide backbone, which inhibits the photoreaction due to spatial separation of the crosslinker side chains. Mixed-matrix membranes (MMMs) with MOFs as additives (fillers) have increased permeabilities and often also selectivities compared to the pure polymer. Incorporation of MOFs into polysulfone and Matrimid® polymers for MMMs gives defect-free membranes with performances similar to the best polymer membranes for gas mixtures, such as O2/N2 H2/CH4, CO2/CH4, H2/CO2, CH4/N2 and CO2/N2 (preferentially permeating gas is named first). The MOF porosity, its particle size and content in the MMM are factors to influence the permeability and the separation performance of the membranes.

  14. Investigation of Cross-Linked and Additive Containing Polymer Materials for Membranes with Improved Performance in Pervaporation and Gas Separation

    PubMed Central

    Hunger, Katharina; Schmeling, Nadine; Jeazet, Harold B. Tanh; Janiak, Christoph; Staudt, Claudia; Kleinermanns, Karl

    2012-01-01

    Pervaporation and gas separation performances of polymer membranes can be improved by crosslinking or addition of metal-organic frameworks (MOFs). Crosslinked copolyimide membranes show higher plasticization resistance and no significant loss in selectivity compared to non-crosslinked membranes when exposed to mixtures of CO2/CH4 or toluene/cyclohexane. Covalently crosslinked membranes reveal better separation performances than ionically crosslinked systems. Covalent interlacing with 3-hydroxypropyldimethylmaleimide as photocrosslinker can be investigated in situ in solution as well as in films, using transient UV/Vis and FTIR spectroscopy. The photocrosslinking yield can be determined from the FTIR-spectra. It is restricted by the stiffness of the copolyimide backbone, which inhibits the photoreaction due to spatial separation of the crosslinker side chains. Mixed-matrix membranes (MMMs) with MOFs as additives (fillers) have increased permeabilities and often also selectivities compared to the pure polymer. Incorporation of MOFs into polysulfone and Matrimid® polymers for MMMs gives defect-free membranes with performances similar to the best polymer membranes for gas mixtures, such as O2/N2 H2/CH4, CO2/CH4, H2/CO2, CH4/N2 and CO2/N2 (preferentially permeating gas is named first). The MOF porosity, its particle size and content in the MMM are factors to influence the permeability and the separation performance of the membranes. PMID:24958427

  15. Linking process, structure, property, and performance for metal-based additive manufacturing: computational approaches with experimental support

    NASA Astrophysics Data System (ADS)

    Smith, Jacob; Xiong, Wei; Yan, Wentao; Lin, Stephen; Cheng, Puikei; Kafka, Orion L.; Wagner, Gregory J.; Cao, Jian; Liu, Wing Kam

    2016-04-01

    Additive manufacturing (AM) methods for rapid prototyping of 3D materials (3D printing) have become increasingly popular with a particular recent emphasis on those methods used for metallic materials. These processes typically involve an accumulation of cyclic phase changes. The widespread interest in these methods is largely stimulated by their unique ability to create components of considerable complexity. However, modeling such processes is exceedingly difficult due to the highly localized and drastic material evolution that often occurs over the course of the manufacture time of each component. Final product characterization and validation are currently driven primarily by experimental means as a result of the lack of robust modeling procedures. In the present work, the authors discuss primary detrimental hurdles that have plagued effective modeling of AM methods for metallic materials while also providing logical speculation into preferable research directions for overcoming these hurdles. The primary focus of this work encompasses the specific areas of high-performance computing, multiscale modeling, materials characterization, process modeling, experimentation, and validation for final product performance of additively manufactured metallic components.

  16. Dynamic SUMOylation is linked to the activity cycles of androgen receptor in the cell nucleus.

    PubMed

    Rytinki, Miia; Kaikkonen, Sanna; Sutinen, Päivi; Paakinaho, Ville; Rahkama, Vesa; Palvimo, Jorma J

    2012-10-01

    Despite of the progress in the molecular etiology of prostate cancer, the androgen receptor (AR) remains the major druggable target for the advanced disease. In addition to hormonal ligands, AR activity is regulated by posttranslational modifications. Here, we show that androgen induces SUMO-2 and SUMO-3 (SUMO-2/3) modification (SUMOylation) of the endogenous AR in prostate cancer cells, which is also reflected in the chromatin-bound receptor. Although only a small percentage of AR is SUMOylated at the steady state, AR SUMOylation sites have an impact on the receptor's stability, intranuclear mobility, and chromatin interactions and on expression of its target genes. Interestingly, short-term proteotoxic and cell stress, such as hyperthermia, that detaches the AR from the chromatin triggers accumulation of the SUMO-2/3-modified AR pool which concentrates into the nuclear matrix compartment. Alleviation of the stress allows rapid reversal of the SUMO-2/3 modifications and the AR to return to the chromatin. In sum, these results suggest that the androgen-induced SUMOylation is linked to the activity cycles of the holo-AR in the nucleus and chromatin binding, whereas the stress-induced SUMO-2/3 modifications sustain the solubility of the AR and protect it from proteotoxic insults in the nucleus.

  17. Feasibility of a multi-component additive for efficient control of activated sludge filamentous bulking.

    PubMed

    Seka, A M; Van De Wiele, T; Verstraete, W

    2001-08-01

    Instantaneous improvement of the settling of bulking filamentous activated sludge can be achieved by the addition of a polymer or a large amount (up to 100% of the MLSS concentration) of talc powder to the sludge. Long-term improvement relies on repeated additions, as these additives have no adverse effects on the causative filaments. A multi-component additive was compared to the traditional additives in lab-scale activated sludge units using three highly filamentous sludges from different industrial treatment plants. The study demonstrated that the multi-component additive was superior to the traditional remedies. It was shown that, in the case of severe filamentous bulking, a single addition of the new additive immediately improved sludge settling and exerted a destructive effect on the causative filamentous bacteria. Thus, the latter additive also ensured a long-term sludge sedimentation improvement. The traditional additives exhibited an immediate and short-term effect. The novel additive also retarded sludge rising due to denitrification and it improved sludge dewaterability. The study revealed Nostocoido limicola II, with slightly hydrophobic cell wall, to be somewhat resistant to the quaternary ammonium salt present as biocide in the additive.

  18. Probing the Role of N-Linked Glycans in the Stability and Activity of Fungal Cellobiohydrolases by Mutational Analysis

    SciTech Connect

    Adney, W. S.; Jeoh, T.; Beckham, G. T.; Chou,Y. C.; Baker, J. O.; Michener, W.; Brunecky, R.; Himmel, M. E.

    2009-01-01

    The filamentous fungi Trichoderma reesei and Penicillium funiculosum produce highly effective enzyme mixtures that degrade the cellulose and hemicellulose components of plant cell walls. Many fungal species produce a glycoside hydrolase family 7 (Cel7A) cellobiohydrolase, a class of enzymes that catalytically process from the reducing end of cellulose. A direct amino acid comparison of these two enzymes shows that they not only have high amino acid homology, but also contain analogous N-linked glycosylation sites on the catalytic domain. We have previously shown (Jeoh et al. in Biotechnol Biofuels, 1:10, 2008) that expression of T. reesei cellobiohydrolase I in a commonly used industrial expression host, Aspergillus niger var. awamori, results in an increase in the amount of N-linked glycosylation of the enzyme, which negatively affects crystalline cellulose degradation activity as well as thermal stability. This complementary study examines the significance of individual N-linked glycans on the surface of the catalytic domain of Cel7A cellobiohydrolases from T. reesei and P. funiculosum by genetically adding or removing N-linked glycosylation motifs using site directed mutagenesis. Modified enzymes, expressed in A. niger var. awamori, were tested for activity and thermal stability. It was concluded that N-linked glycans in peptide loops that form part of the active site tunnel have the greatest impact on both thermal stability and enzymatic activity on crystalline cellulose for both the T. reesei and P. funiculosum Cel7A enzymes. Specifically, for the Cel7A T. reesei enzyme expressed in A. niger var. awamori, removal of the N384 glycosylation site yields a mutant with 70% greater activity after 120 h compared to the heterologously expressed wild type T. reesei enzyme. In addition, similar activity improvements were found to be associated with the addition of a new glycosylation motif at N194 in P. funiculosum. This mutant also exhibits 70% greater activity after

  19. Familial Vulnerability to ADHD Affects Activity in the Cerebellum in Addition to the Prefrontal Systems

    ERIC Educational Resources Information Center

    Mulder, Martijn J.; Baeyens, Dieter; Davidson, Matthew C.; Casey, B. J.; Van Den Ban, Els; Van Engeland, Herman; Durston, Sarah

    2008-01-01

    The study examines whether cerebellar systems are sensitive to familial risk for ADHD in addition to frontostriatal circuitry. The results conclude that familial vulnerability to ADHD affects activity in both the prefrontal cortex and cerebellum.

  20. Autosomal and X-Linked Additive Genetic Variation for Lifespan and Aging: Comparisons Within and Between the Sexes in Drosophila melanogaster.

    PubMed

    Griffin, Robert M; Schielzeth, Holger; Friberg, Urban

    2016-12-07

    Theory makes several predictions concerning differences in genetic variation between the X chromosome and the autosomes due to male X hemizygosity. The X chromosome should: (i) typically show relatively less standing genetic variation than the autosomes, (ii) exhibit more variation in males compared to females because of dosage compensation, and (iii) potentially be enriched with sex-specific genetic variation. Here, we address each of these predictions for lifespan and aging in Drosophila melanogaster To achieve unbiased estimates of X and autosomal additive genetic variance, we use 80 chromosome substitution lines; 40 for the X chromosome and 40 combining the two major autosomes, which we assay for sex-specific and cross-sex genetic (co)variation. We find significant X and autosomal additive genetic variance for both traits in both sexes (with reservation for X-linked variation of aging in females), but no conclusive evidence for depletion of X-linked variation (measured through females). Males display more X-linked variation for lifespan than females, but it is unclear if this is due to dosage compensation since also autosomal variation is larger in males. Finally, our results suggest that the X chromosome is enriched for sex-specific genetic variation in lifespan but results were less conclusive for aging overall. Collectively, these results suggest that the X chromosome has reduced capacity to respond to sexually concordant selection on lifespan from standing genetic variation, while its ability to respond to sexually antagonistic selection may be augmented.

  1. Autosomal and X-Linked Additive Genetic Variation for Lifespan and Aging: Comparisons Within and Between the Sexes in Drosophila melanogaster

    PubMed Central

    Griffin, Robert M.; Schielzeth, Holger; Friberg, Urban

    2016-01-01

    Theory makes several predictions concerning differences in genetic variation between the X chromosome and the autosomes due to male X hemizygosity. The X chromosome should: (i) typically show relatively less standing genetic variation than the autosomes, (ii) exhibit more variation in males compared to females because of dosage compensation, and (iii) potentially be enriched with sex-specific genetic variation. Here, we address each of these predictions for lifespan and aging in Drosophila melanogaster. To achieve unbiased estimates of X and autosomal additive genetic variance, we use 80 chromosome substitution lines; 40 for the X chromosome and 40 combining the two major autosomes, which we assay for sex-specific and cross-sex genetic (co)variation. We find significant X and autosomal additive genetic variance for both traits in both sexes (with reservation for X-linked variation of aging in females), but no conclusive evidence for depletion of X-linked variation (measured through females). Males display more X-linked variation for lifespan than females, but it is unclear if this is due to dosage compensation since also autosomal variation is larger in males. Finally, our results suggest that the X chromosome is enriched for sex-specific genetic variation in lifespan but results were less conclusive for aging overall. Collectively, these results suggest that the X chromosome has reduced capacity to respond to sexually concordant selection on lifespan from standing genetic variation, while its ability to respond to sexually antagonistic selection may be augmented. PMID:27678519

  2. Linking perception to neural activity as measured by visual evoked potentials.

    PubMed

    Norcia, Anthony M

    2013-11-01

    Linking propositions have played an important role in refining our understanding of the relationship between neural activity and perception. Over the last 40 years, visual evoked potentials (VEPs) have been used in many different ways to address questions of the relationship between neural activity and perception. This review organizes and discusses this research within the linking proposition framework developed by Davida Teller, and her colleagues. A series of examples from the VEP literature illustrates each of the five classes of linking propositions originally proposed by Davida Teller. The related concept of the bridge locus-the site at which neural activity can be said to first be proscriptive of perception-is discussed and a suggestion is made that the concept be expanded to include an evolution over time and cortical area.

  3. 42 CFR 424.516 - Additional provider and supplier requirements for enrolling and maintaining active enrollment...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Additional provider and supplier requirements for... Billing Privileges § 424.516 Additional provider and supplier requirements for enrolling and maintaining... active enrollment status for a provider or supplier when that provider or supplier certifies that...

  4. Community shifts of actively growing lake bacteria after N-acetyl-glucosamine addition: improving the BrdU-FACS method.

    PubMed

    Tada, Yuya; Grossart, Hans-Peter

    2014-02-01

    In aquatic environments, community dynamics of bacteria, especially actively growing bacteria (AGB), are tightly linked with dissolved organic matter (DOM) quantity and quality. We analyzed the community dynamics of DNA-synthesizing and accordingly AGB by linking an improved bromodeoxyuridine immunocytochemistry approach with fluorescence-activated cell sorting (BrdU-FACS). FACS-sorted cells of even oligotrophic ecosystems in winter were characterized by 16S rRNA gene analysis. In incubation experiments, we examined community shifts of AGB in response to the addition of N-acetyl-glucosamine (NAG), one of the most abundant aminosugars in aquatic systems. Our improved BrdU-FACS analysis revealed that AGB winter communities of oligotrophic Lake Stechlin (northeastern Germany) substantially differ from those of total bacteria and consist of Alpha-, Beta-, Gamma-, Deltaproteobacteria, Actinobacteria, Candidatus OP10 and Chloroflexi. AGB populations with different BrdU-fluorescence intensities and cell sizes represented different phylotypes suggesting that single-cell growth potential varies at the taxon level. NAG incubation experiments demonstrated that a variety of widespread taxa related to Alpha-, Beta-, Gammaproteobacteria, Bacteroidetes, Actinobacteria, Firmicutes, Planctomycetes, Spirochaetes, Verrucomicrobia and Chloroflexi actively grow in the presence of NAG. The BrdU-FACS approach enables detailed phylogenetic studies of AGB and, thus, to identify those phylotypes which are potential key players in aquatic DOM cycling.

  5. Subsidence and Collapse Activity in Arabia Terra, Mars: Which Link with Magmatic Activity?

    NASA Astrophysics Data System (ADS)

    Mangold, N.; Howard, A. D.

    2014-12-01

    Collapsed terrains have been observed using Viking images in the northern part of Arabia Terra from Ismenius Lacus to Deuteronilus Mensae. Recent interpretations of some of these depressions as explosive volcanoes (Michalski and Bleacher, 2013) have renewed the interest for this region. However, recent observations also show the discovery in this region of a series of outflow channels named Okavango Valles (Mangold and Howard, 2013). These channels formed in the Hesperian through catastrophic flows having deposited sediments as deltas in ephemeral lakes. The source area of these channels takes place in a region of widespread depressions and local collapse pits. A continuum of landforms exists from broad depressions (~100 km in length and 100s m in depth) and sharper collapse structures (<100 km in diameter). Given the link between these depressions and the presence of outflow channels, we interpret the collapse structures as resulting from a specific lithology with volatile-rich sediments (or megaregolith) buried at depth. Collapse may be due either to the melting of subsurface ice, or subsurface flows triggered by a change in the groundwater table, or the (less likely) dissolution of buried chemical sediments. Magmatic activity is not excluded: a regionally enhanced thermal flux during the Hesperian could have triggered ground ice melting, and could have initiated subsidence subsequently, but explosive volcanism at the surface is not necessary to explain the presence of large collapsed terrains. Michalski, J. and J. Bleacher, 2013. Supervolcanoes within an ancient volcanic province in Arabia Terra, Mars, Nature, doi:10.1038/nature12482 Mangold N., and A. D. Howard, 2013. Outflow channels with deltaic deposits in Ismenius Lacus, Mars, Icarus, doi.org/10.1016/j.icarus.2013.05.040

  6. A comparison of high-speed links, their commercial support and ongoing R D activities

    SciTech Connect

    Gonzalez, H.L.; Barsotti, E. ); Zimmermann, S. Rio Grande do Sul Univ., Porto Alegre, RS ); Nomachi, M.; Sasaki, O. )

    1992-10-01

    Technological advances and a demanding market have forced the development of higher bandwidth communication standards for networks, data links and busses. Most of these emerging standards are gathering enough momentum that their widespread availability and lower prices are anticipated. The hardware and software that support the physical media for most of these links is currently available, allowing the user community to implement fairly high-bandwidth data links and networks with commercial components. Also, switches needed to support these networks are available or being developed. The commercial suppose of high-bandwidth data links, networks and switching fabrics provides a powerful base for the implementation of high-bandwidth data acquisition systems. A large data acquisition system like the one for the Solenoidal Detector Collaboration (SDC) at the SSC can benefit from links and networks that support an integrated systems engineering approach, for initialization, downloading, diagnostics, monitoring, hardware integration and event data readout. The issue that our current work addresses is the possibility of having a channel/network that satisfies the requirements of an integrated data acquisition system. In this paper we present a brief description of high-speed communication links and protocols that we consider of interest for high energy physic High Performance Parallel Interface (HIPPI). Serial HIPPI, Fibre Channel (FC) and Scalable Coherent Interface (SCI). In addition, the initial work required to implement an SDC-like data acquisition system is described.

  7. A comparison of high-speed links, their commercial support and ongoing R&D activities

    SciTech Connect

    Gonzalez, H.L.; Barsotti, E.; Zimmermann, S. |; Nomachi, M.; Sasaki, O.

    1992-10-01

    Technological advances and a demanding market have forced the development of higher bandwidth communication standards for networks, data links and busses. Most of these emerging standards are gathering enough momentum that their widespread availability and lower prices are anticipated. The hardware and software that support the physical media for most of these links is currently available, allowing the user community to implement fairly high-bandwidth data links and networks with commercial components. Also, switches needed to support these networks are available or being developed. The commercial suppose of high-bandwidth data links, networks and switching fabrics provides a powerful base for the implementation of high-bandwidth data acquisition systems. A large data acquisition system like the one for the Solenoidal Detector Collaboration (SDC) at the SSC can benefit from links and networks that support an integrated systems engineering approach, for initialization, downloading, diagnostics, monitoring, hardware integration and event data readout. The issue that our current work addresses is the possibility of having a channel/network that satisfies the requirements of an integrated data acquisition system. In this paper we present a brief description of high-speed communication links and protocols that we consider of interest for high energy physic High Performance Parallel Interface (HIPPI). Serial HIPPI, Fibre Channel (FC) and Scalable Coherent Interface (SCI). In addition, the initial work required to implement an SDC-like data acquisition system is described.

  8. Linking rapid erosion of the Mekong River delta to human activities.

    PubMed

    Anthony, Edward J; Brunier, Guillaume; Besset, Manon; Goichot, Marc; Dussouillez, Philippe; Nguyen, Van Lap

    2015-10-08

    As international concern for the survival of deltas grows, the Mekong River delta, the world's third largest delta, densely populated, considered as Southeast Asia's most important food basket, and rich in biodiversity at the world scale, is also increasingly affected by human activities and exposed to subsidence and coastal erosion. Several dams have been constructed upstream of the delta and many more are now planned. We quantify from high-resolution SPOT 5 satellite images large-scale shoreline erosion and land loss between 2003 and 2012 that now affect over 50% of the once strongly advancing >600 km-long delta shoreline. Erosion, with no identified change in the river's discharge and in wave and wind conditions over this recent period, is consistent with: (1) a reported significant decrease in coastal surface suspended sediment from the Mekong that may be linked to dam retention of its sediment, (2) large-scale commercial sand mining in the river and delta channels, and (3) subsidence due to groundwater extraction. Shoreline erosion is already responsible for displacement of coastal populations. It is an additional hazard to the integrity of this Asian mega delta now considered particularly vulnerable to accelerated subsidence and sea-level rise, and will be exacerbated by future hydropower dams.

  9. Linking rapid erosion of the Mekong River delta to human activities

    PubMed Central

    Anthony, Edward J.; Brunier, Guillaume; Besset, Manon; Goichot, Marc; Dussouillez, Philippe; Nguyen, Van Lap

    2015-01-01

    As international concern for the survival of deltas grows, the Mekong River delta, the world’s third largest delta, densely populated, considered as Southeast Asia’s most important food basket, and rich in biodiversity at the world scale, is also increasingly affected by human activities and exposed to subsidence and coastal erosion. Several dams have been constructed upstream of the delta and many more are now planned. We quantify from high-resolution SPOT 5 satellite images large-scale shoreline erosion and land loss between 2003 and 2012 that now affect over 50% of the once strongly advancing >600 km-long delta shoreline. Erosion, with no identified change in the river’s discharge and in wave and wind conditions over this recent period, is consistent with: (1) a reported significant decrease in coastal surface suspended sediment from the Mekong that may be linked to dam retention of its sediment, (2) large-scale commercial sand mining in the river and delta channels, and (3) subsidence due to groundwater extraction. Shoreline erosion is already responsible for displacement of coastal populations. It is an additional hazard to the integrity of this Asian mega delta now considered particularly vulnerable to accelerated subsidence and sea-level rise, and will be exacerbated by future hydropower dams. PMID:26446752

  10. Waste activated sludge hydrolysis and acidification: A comparison between sodium hydroxide and steel slag addition.

    PubMed

    Zhang, Ying; Zhang, Chaojie; Zhang, Xuan; Feng, Leiyu; Li, Yongmei; Zhou, Qi

    2016-10-01

    Alkaline treatment with steel slag and NaOH addition were investigated under different pH conditions for the fermentation of waste activated sludge. Better performance was achieved in steel slag addition scenarios for both sludge hydrolysis and acidification. More solubilization of organic matters and much production of higher VFA (volatile fatty acid) in a shorter time can be achieved at pH10 when adjusted by steel slag. Higher enzyme activities were also observed in steel slag addition scenarios under the same pH conditions. Phosphorus concentration in the supernatant increased with fermentation time and pH in NaOH addition scenarios, while in contrast most phosphorus was released and captured by steel slag simultaneously in steel slag addition scenarios. These results suggest that steel slag can be used as a substitute for NaOH in sludge alkaline treatment.

  11. Activation and Stabilization of Olive Recombinant 13-Hydroperoxide Lyase Using Selected Additives.

    PubMed

    Jacopini, Sabrina; Vincenti, Sophie; Mariani, Magali; Brunini-Bronzini de Caraffa, Virginie; Gambotti, Claude; Desjobert, Jean-Marie; Muselli, Alain; Costa, Jean; Tomi, Félix; Berti, Liliane; Maury, Jacques

    2016-12-24

    The stabilization of olive recombinant hydroperoxide lyases (rHPLs) was investigated using selected chemical additives. Two rHPLs were studied: HPL full-length and HPL with its chloroplast transit peptide deleted (matured HPL). Both olive rHPLs are relatively stable at 4 °C, and enzyme activity can be preserved (about 100% of the rHPL activities are maintained) during 5 weeks of storage at -20 or at -80 °C in the presence of glycerol (10%, v/v). Among the additives used in this study, glycine (2.5% w/v), NaCl (0.5 M), and Na2SO4 (0.25 M) provided the highest activation of HPL full-length activity, while the best matured HPL activity was obtained with Na2SO4 (0.25 M) and NaCl (1 M). Although the inactivation rate constants (k) showed that these additives inactivate both rHPLs, their use is still relevant as they strongly increase HPL activity. Results of C6-aldehyde production assays also showed that glycine, NaCl, and Na2SO4 are appropriate additives and that NaCl appears to be the best additive, at least for hexanal production.

  12. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model.

    PubMed

    Sano, Shigetoshi; Chan, Keith Syson; Carbajal, Steve; Clifford, John; Peavey, Mary; Kiguchi, Kaoru; Itami, Satoshi; Nickoloff, Brian J; DiGiovanni, John

    2005-01-01

    Here we report that epidermal keratinocytes in psoriatic lesions are characterized by activated Stat3. Transgenic mice with keratinocytes expressing a constitutively active Stat3 (K5.Stat3C mice) develop a skin phenotype either spontaneously, or in response to wounding, that closely resembles psoriasis. Keratinocytes from K5.Stat3C mice show upregulation of several molecules linked to the pathogenesis of psoriasis. In addition, the development of psoriatic lesions in K5.Stat3C mice requires cooperation between Stat3 activation in keratinocytes and activated T cells. Finally, abrogation of Stat3 function by a decoy oligonucleotide inhibits the onset and reverses established psoriatic lesions in K5.Stat3C mice. Thus, targeting Stat3 may be potentially therapeutic in the treatment of psoriasis.

  13. Changes of soil bacterial activities and functions after different N additions in a temperate forest.

    PubMed

    Guo, Peng; Han, Tiwen; Zhang, Li; Li, Shushan; Ma, Dongzhu; Du, Yuhan

    2017-02-01

    It has been shown that different nitrogen (N) addition led to various influences on soil microbial activities in forest ecosystems; however, the changes of bacteria were still unclear. In this work, inorganic N (NH4NO3) and organic N (urea and glycine) were fertilized with different ratios (5:0, 1:4, 3:2, 2:3, and 1:4) on temperate forest soils, while fungicide (cycloheximide) was simultaneously added on half of each treatment to inhibit fungal activities (leaving only bacteria). After a 3-year field experiment, soil samples were harvested, then microbial enzymatic activities involved in carbon (C), and N and phosphorus (P) cycles were determined. Under laboratory conditions, four purified bacteria which were isolated from sample site had been inoculated in sterilized soils under different N types and enzymatic activities were assayed after 90-day incubation. The results showed that cellulase and polyphenol oxidase activities of non-fungicide-added treatments increased after N addition and greater organic N accelerated the increases. However, these enzymatic activities of fungicide-added treatments were not significantly influenced by N addition and N types. It may be due to the insufficient ability of bacteria to synthesize enough enzymes to decompose complex organic C (such as cellulose and lignin) into available compound, although N-limitation was alleviated. Alkaline phosphatase activities increased after N addition in both non-fungicide-added and fungicide-added treatments, and the acceleration on bacterial alkaline phosphatase activities was even greater. Furthermore, organic N showed at least 2.5 times promotion on bacteria alkaline phosphatase than those of inorganic N, which indicated greater alleviation of bacterial P-limitation after the addition of organic N. All the results indicated that soil bacteria may be seriously limited by soil available C but become the dominant decomposer of the complex P compounds after N addition, particularly greater

  14. N-Linked Glycosylation of Protease-activated Receptor-1 Second Extracellular Loop

    PubMed Central

    Soto, Antonio G.; Trejo, JoAnn

    2010-01-01

    Protease-activated receptor-1 (PAR1) contains five N-linked glycosylation consensus sites as follows: three residing in the N terminus and two localized on the surface of the second extracellular loop (ECL2). To study the effect of N-linked glycosylation in the regulation of PAR1 signaling and trafficking, we generated mutants in which the critical asparagines of the consensus sites were mutated. Here, we report that both the PAR1 N terminus and ECL2 serve as sites for N-linked glycosylation but have different functions in the regulation of receptor signaling and trafficking. N-Linked glycosylation of the PAR1 N terminus is important for transport to the cell surface, whereas the PAR1 mutant lacking glycosylation at ECL2 (NA ECL2) trafficked to the cell surface like the wild-type receptor. However, activated PAR1 NA ECL2 mutant internalization was impaired compared with wild-type receptor, whereas constitutive internalization of unactivated receptor remained intact. Remarkably, thrombin-activated PAR1 NA ECL2 mutant displayed an enhanced maximal signaling response compared with wild-type receptor. The increased PAR1 NA ECL2 mutant signaling was not due to defects in the ability of thrombin to cleave the receptor or signal termination mechanisms. Rather, the PAR1 NA ECL2 mutant displayed a greater efficacy in thrombin-stimulated G protein signaling. Thus, N-linked glycosylation of the PAR1 extracellular surface likely influences ligand docking interactions and the stability of the active receptor conformation. Together, these studies strongly suggest that N-linked glycosylation of PAR1 at the N terminus versus the surface of ECL2 serves distinct functions critical for proper regulation of receptor trafficking and the fidelity of thrombin signaling. PMID:20368337

  15. Activation of RNA polymerase II by topologically linked DNA-tracking proteins

    PubMed Central

    Ouhammouch, Mohamed; Sayre, Michael H.; Kadonaga, James T.; Geiduschek, E. Peter

    1997-01-01

    Almost all proteins mediating transcriptional activation from promoter-distal sites attach themselves, directly or indirectly, to specific DNA sequence elements. Nevertheless, a single instance of activation by a prokaryotic topologically linked DNA-tracking protein has also been demonstrated. The scope of the latter class of transcriptional activators is broadened in this work. Heterologous fusion proteins linking the transcriptional activation domain of herpes simplex virus VP16 protein to the sliding clamp protein β of the Escherichia coli DNA polymerase III holoenzyme are shown to function as topologically DNA-linked activators of yeast and Drosophila RNA polymerase II. The β:VP16 fusion proteins must be loaded onto DNA by the clamp-loading E. coli γ complex to be transcriptionally active, but they do not occupy fixed sites on the DNA. The DNA-loading sites of these activators have all the properties of enhancers: they can be inverted and their locations relative to the transcriptional start site are freely adjustable. PMID:9192631

  16. Additive and synergistic antiandrogenic activities of mixtures of azol fungicides and vinclozolin

    SciTech Connect

    Christen, Verena; Crettaz, Pierre; Fent, Karl

    2014-09-15

    Objective: Many pesticides including pyrethroids and azole fungicides are suspected to have an endocrine disrupting property. At present, the joint activity of compound mixtures is only marginally known. Here we tested the hypothesis that the antiandrogenic activity of mixtures of azole fungicides can be predicted by the concentration addition (CA) model. Methods: The antiandrogenic activity was assessed in MDA-kb2 cells. Following assessing single compounds activities mixtures of azole fungicides and vinclozolin were investigated. Interactions were analyzed by direct comparison between experimental and estimated dose–response curves assuming CA, followed by an analysis by the isobole method and the toxic unit approach. Results: The antiandrogenic activity of pyrethroids deltamethrin, cypermethrin, fenvalerate and permethrin was weak, while the azole fungicides tebuconazole, propiconazole, epoxiconazole, econazole and vinclozolin exhibited strong antiandrogenic activity. Ten binary and one ternary mixture combinations of five antiandrogenic fungicides were assessed at equi-effective concentrations of EC{sub 25} and EC{sub 50}. Isoboles indicated that about 50% of the binary mixtures were additive and 50% synergistic. Synergism was even more frequently indicated by the toxic unit approach. Conclusion: Our data lead to the conclusion that interactions in mixtures follow the CA model. However, a surprisingly high percentage of synergistic interactions occurred. Therefore, the mixture activity of antiandrogenic azole fungicides is at least additive. Practice: Mixtures should also be considered for additive antiandrogenic activity in hazard and risk assessment. Implications: Our evaluation provides an appropriate “proof of concept”, but whether it equally translates to in vivo effects should further be investigated. - Highlights: • Humans are exposed to pesticide mixtures such as pyrethroids and azole fungicides. • We assessed the antiandrogenicity of

  17. Graphene as conductive additives in binderless activated carbon electrodes for power enhancement of supercapacitor

    NASA Astrophysics Data System (ADS)

    Nor, N. S. M.; Deraman, M.; Suleman, M.; Norizam, M. D. M.; Basri, N. H.; Sazali, N. E. S.; Hamdan, E.; Hanappi, M. F. Y. M.; Tajuddin, N. S. M.; Othman, M. A. R.; Shamsudin, S. A.; Omar, R.

    2016-11-01

    Carbon based supercapacitor electrodes from composite of binderless activated carbon and graphene as a conductive additive were fabricated with various amount of graphene (0, 2, 4, 6, 8 and 10 wt%). Graphene was mixed in self-adhesive carbon grains produced from pre-carbonized powder derived from fibers of oil palm empty fruit bunches and converted into green monoliths (GMs). The GMs were carbonized (N2) and activated (CO2) to produce activated carbon monoliths (ACMs) electrodes. Porosity characterizations by nitrogen adsorption-desorption isotherm method shows that the pore characteristics of the ACMs are influenced by the graphene additive. The results of galvanostatic charge-discharge tests carried out on the supercapacitor cells fabricated using these electrodes shows that the addition of graphene additive (even in small amount) decreases the equivalent series resistance and enhances the specific power of the cells but significantly lowers the specific capacitance. The supercapacitor cell constructed with the electrode containing 4 wt % of graphene offers the maximum power (175 W kg-1) which corresponds to an improvement of 55%. These results demonstrate that the addition of graphene as conductive additive in activated carbon electrodes can enhance the specific power of the supercapacitor.

  18. Fibromodulin Interacts with Collagen Cross-linking Sites and Activates Lysyl Oxidase*

    PubMed Central

    Bihan, Dominique; Bonna, Arkadiusz; Rubin, Kristofer; Farndale, Richard W.

    2016-01-01

    The hallmark of fibrotic disorders is a highly cross-linked and dense collagen matrix, a property driven by the oxidative action of lysyl oxidase. Other fibrosis-associated proteins also contribute to the final collagen matrix properties, one of which is fibromodulin. Its interactions with collagen affect collagen cross-linking, packing, and fibril diameter. We investigated the possibility that a specific relationship exists between fibromodulin and lysyl oxidase, potentially imparting a specific collagen matrix phenotype. We mapped the fibromodulin-collagen interaction sites using the collagen II and III Toolkit peptide libraries. Fibromodulin interacted with the peptides containing the known collagen cross-linking sites and the MMP-1 cleavage site in collagens I and II. Interestingly, the interaction sites are closely aligned within the quarter-staggered collagen fibril, suggesting a multivalent interaction between fibromodulin and several collagen helices. Furthermore, we detected an interaction between fibromodulin and lysyl oxidase (a major collagen cross-linking enzyme) and mapped the interaction site to 12 N-terminal amino acids on fibromodulin. This interaction also increases the activity of lysyl oxidase. Together, the data suggest a fibromodulin-modulated collagen cross-linking mechanism where fibromodulin binds to a specific part of the collagen domain and also forms a complex with lysyl oxidase, targeting the enzyme toward specific cross-linking sites. PMID:26893379

  19. Fibromodulin Interacts with Collagen Cross-linking Sites and Activates Lysyl Oxidase.

    PubMed

    Kalamajski, Sebastian; Bihan, Dominique; Bonna, Arkadiusz; Rubin, Kristofer; Farndale, Richard W

    2016-04-08

    The hallmark of fibrotic disorders is a highly cross-linked and dense collagen matrix, a property driven by the oxidative action of lysyl oxidase. Other fibrosis-associated proteins also contribute to the final collagen matrix properties, one of which is fibromodulin. Its interactions with collagen affect collagen cross-linking, packing, and fibril diameter. We investigated the possibility that a specific relationship exists between fibromodulin and lysyl oxidase, potentially imparting a specific collagen matrix phenotype. We mapped the fibromodulin-collagen interaction sites using the collagen II and III Toolkit peptide libraries. Fibromodulin interacted with the peptides containing the known collagen cross-linking sites and the MMP-1 cleavage site in collagens I and II. Interestingly, the interaction sites are closely aligned within the quarter-staggered collagen fibril, suggesting a multivalent interaction between fibromodulin and several collagen helices. Furthermore, we detected an interaction between fibromodulin and lysyl oxidase (a major collagen cross-linking enzyme) and mapped the interaction site to 12 N-terminal amino acids on fibromodulin. This interaction also increases the activity of lysyl oxidase. Together, the data suggest a fibromodulin-modulated collagen cross-linking mechanism where fibromodulin binds to a specific part of the collagen domain and also forms a complex with lysyl oxidase, targeting the enzyme toward specific cross-linking sites.

  20. Hydroxylamine addition impact to Nitrosomonas europaea activity in the presence of monochloramine.

    PubMed

    Wahman, David G; Speitel, Gerald E

    2015-01-01

    In drinking water, monochloramine may promote ammonia–oxidizing bacteria (AOB) growth because of concurrent ammonia presence. AOB use (i) ammonia monooxygenase for biological ammonia oxidation to hydroxylamine and (ii) hydroxylamine oxidoreductase for biological hydroxylamine oxidation to nitrite. In addition, monochloramine and hydroxylamine abiotically react, providing AOB a potential benefit by removing the disinfectant (monochloramine) and releasing growth substrate (ammonia). Alternatively and because biological hydroxylamine oxidation supplies the electrons (reductant) required for biological ammonia oxidation, the monochloramine/hydroxylamine abiotic reaction represents a possible inactivation mechanism by consuming hydroxylamine and inhibiting reductant generation. To investigate the abiotic monochloramine and hydroxylamine reaction's impact on AOB activity, the current study used batch experiments with Nitrosomonas europaea (AOB pure culture), ammonia, monochloramine, and hydroxylamine addition. To decipher whether hydroxylamine addition benefitted N. europaea activity by (i) removing monochloramine and releasing free ammonia or (ii) providing an additional effect (possibly the aforementioned reductant source), a previously developed cometabolism model was coupled with an abiotic monochloramine and hydroxylamine model for data interpretation. N. europaea maintained ammonia oxidizing activity when hydroxylamine was added before complete ammonia oxidation cessation. The impact could not be accounted for by monochloramine removal and free ammonia release alone and was concentration dependent for both monochloramine and hydroxylamine. In addition, a preferential negative impact occurred for ammonia versus hydroxylamine oxidation. These results suggest an additional benefit of exogenous hydroxylamine addition beyond monochloramine removal and free ammonia release, possibly providing reductant generation.

  1. Linking Obesity and Activity Level with Children's Television and Video Game Use

    ERIC Educational Resources Information Center

    Vandewater, Elizabeth A.; Shim, Mi-suk; Caplovitz, Allison G.

    2004-01-01

    This study examined the links between childhood obesity, activity participation and television and video game use in a nationally representative sample of children (N=2831) ages 1-12 using age-normed body mass index (BMI) ratings. Results indicated that while television use was not related to children's weight status, video game use was. Children…

  2. Links between Older and Younger Adolescent Siblings' Adjustment: The Moderating Role of Shared Activities

    ERIC Educational Resources Information Center

    Tucker, Corinna Jenkins; McHale, Susan M.; Crouter, Ann C.

    2008-01-01

    Siblings' constructive and unstructured shared activities were examined as moderators of the links between first- and second-born siblings' adjustment across a two-year period in adolescence. Siblings (N = 189 dyads) reported on their depression, peer competency, self worth during home interviews, and their time together in constructive (e.g.,…

  3. Active dentate granule cells encode experience to promote the addition of adult-born hippocampal neurons.

    PubMed

    Kirschen, Gregory W; Shen, Jia; Tian, Mu; Schroeder, Bryce; Wang, Jia; Man, Guoming; Wu, Song; Ge, Shaoyu

    2017-04-03

    The continuous addition of new dentate granule cells, exquisitely regulated by brain activity, renders the hippocampus plastic. However, how neural circuits encode experiences to impact the addition of adult-born neurons remains unknown. Here, we used endoscopic Ca(2+) imaging to track the real-time activity of individual dentate granule cells in freely-behaving mice. For the first time, we found that active dentate granule cells responded to a novel experience by preferentially increasing their Ca(2+) event frequency. This elevated activity, which we found to be associated with object exploration, returned to baseline by one hour in the same environment, but could be dishabituated via introduction to a novel environment. To seamlessly transition between environments, we next established a freely-controllable virtual reality system for unrestrained mice. We again observed increased firing of active neurons in a virtual enriched environment. Interestingly, multiple novel virtual experiences accumulatively increased the number of newborn neurons when compared to a single experience. Finally, optogenetic silencing of existing dentate granule cells during novel environmental exploration perturbed experience-induced neuronal addition. Together, our study shows that the adult brain conveys novel, enriched experiences to increase the addition of adult-born hippocampal neurons by increasing the firing of active dentate granule cells.SIGNIFICANCE STATEMENTAdult brains are constantly reshaping themselves from synapses to circuits as we encounter novel experiences from moment to moment. Importantly, this reshaping includes the addition of newborn hippocampal neurons. However, it remains largely unknown how our circuits encode experience-induced brain activity to govern the addition of new hippocampal neurons. By coupling in vivo Ca(2+) imaging of dentate granule neurons with a novel unrestrained virtual reality system for rodents, we discovered that a new experience rapidly

  4. Detection, quantification, and glycotyping of prion protein in specifically activated enzyme-linked immunosorbent assay plates.

    PubMed

    Triantaphyllidou, I E; Sklaviadis, T; Vynios, D H

    2006-12-15

    The conversion of a normal glycoprotein, prion protein (PrP(C)), to its abnormal protease-resistant isoform (PrP(Sc)) seems to be one of the main factors underlying the pathogenesis of spongiform encephalopathies. There are many studies indicating that PrP interacts with glycosaminoglycans, and we exploited this interaction to develop a sensitive solid phase assay for detection of both PrP forms. Glycosaminoglycans, such as chondroitin sulfate and heparin, were immobilized by their negative charge to enzyme-linked immunosorbent assay (ELISA) plate wells activated by glutaraldehyde and spermine. PrP in the samples examined (recombinant PrP or tissue homogenate) was allowed to interact with glycans. The interaction of recombinant PrP was more efficient against immobilized chondroitin sulfate of type A, and a linear correlation with concentration was demonstrated. From this curve, the concentration of each one of the PrP isoforms in biological samples can be determined. In addition, and taking into account that glycosylation of prion protein is species specific, we used similarly activated ELISA plate wells to determine different PrP glycoforms. A monoclonal antibody against PrP was immobilized, and PrP present in the samples (brain homogenates) was bound and visualized by various lectins. The most interesting outcome of the study is the differential binding of ricinus communis agglutinin I to the normal and scrapie brain homogenates. Dattura stramonium lectin and wheat germ agglutinin seem to bind almost equally to both samples, and all three have an increased sensitivity to PrP(Sc) after proteinase K digestion.

  5. Extravehicular Activity/Air Traffic Control (EVA/ATC) test report. [communication links to the astronaut

    NASA Technical Reports Server (NTRS)

    Tomaro, D. J.

    1982-01-01

    During extravehicular activity (EVA), communications between the EVA astronaut and the space shuttle orbiter are maintained by means of transceiver installed in the environmental support system backpack. Onboard the orbiter, a transceiver line replaceable unit and its associated equipment performs the task of providing a communications link to the astronaut in the extravehicular activity/air traffic control (EVA/ATC) mode. Results of the acceptance tests that performed on the system designed and fabricated for EVA/ATC testing are discussed.

  6. Assessment of additive/nonadditive effects in structure-activity relationships: implications for iterative drug design.

    PubMed

    Patel, Yogendra; Gillet, Valerie J; Howe, Trevor; Pastor, Joaquin; Oyarzabal, Julen; Willett, Peter

    2008-12-11

    Free-Wilson (FW) analysis is common practice in medicinal chemistry and is based on the assumption that the contributions to activity made by substituents at different substitution positions are additive. We analyze eight near complete combinatorial libraries assayed on several different biological response(s) (GPCR, ion channel, kinase and P450 targets) and show that only half-exhibit clear additive behavior, which leads us to question the concept of additivity that is widely taken for granted in drug discovery. Next, we report a series of retrospective experiments in which subsets are extracted from the libraries for FW analysis to determine the minimum attributes (size, distribution of substituents, and activity range) necessary to reach the same conclusion about additive/nonadditive effects. These attributes can provide guidelines on when it is appropriate to apply FW analysis as well as for library design, and they also have important implications for further steps in iterative drug design.

  7. Activity related to the carcinogenicity of plastic additives in the benzophenone group.

    PubMed

    Nakajima, Daisuke; Asada, Shin; Kageyama, Shiho; Yamamoto, Takashi; Kuramochi, Hidetoshi; Tanaka, Noriho; Takeda, Ken; Goto, Sumio

    2006-06-01

    This study examines the activities relating to the carcinogenicity of six types of benzophenone derivatives (benzophenone, 2-hydroxy-4-octyloxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone and 2,2'-dihydroxy-4,4'-dimethoxybenzophenone) currently used in plastic products as additives to serve as ultraviolet absorbing agents. The evaluation of the initiation activity used a light absorption umu-test, a luminescent umu-test and the Ames test. The promotion activity was examined by a Bhas assay, a method that uses Bhas 42 cells for the formation of transformation foci. The luminescent umu-test indicated positive initiation activity of 2-hydroxy-4-methoxybenzophenone, and pseudo-positive activity of 2,4-dihydroxybenzophenone and 2,2'-dihydroxy-4-methoxybenzophenone. In the Ames test, 2-hydroxy-4-octyloxybenzophenone showed pseudo-positive initiation activity. Conversely, 2,4-dihydroxybenzophenone indicated weak promotion activity at 10 microg/ml concentration.

  8. [Effects of nitrogen addition on soil physico-chemical properties and enzyme activities in desertified steppe].

    PubMed

    Su, Jie-Qiong; Li, Xin-Rong; Bao, Jing-Ting

    2014-03-01

    To investigate the impacts of nitrogen (N) enrichment on soil physico-chemical property and soil enzyme activities in desert ecosystems, a field experiment by adding N at 0, 1.75, 3.5, 7, or 14 g N x m(-2) a(-1) was conducted in a temperate desert steppe in the southeastern fringe of the Tengger Desert. The results showed that N addition led to accumulations of total N, NO(3-)-N, NH(4+)-N, and available N in the upper soil (0-10 cm) and subsoil (10-20 cm), however, reductions in soil pH were observed, causing soil acidification to some extent. N addition pronouncedly inhibited soil enzyme activities, which were different among N addition levels, soil depths, and years, respectively. Soil enzyme activities were significantly correlated with the soil N level, soil pH, and soil moisture content, respectively.

  9. Effect of Exogenous Phytase Addition on Soil Phosphatase Activities: a Fluorescence Spectroscopy Study.

    PubMed

    Yang, Xiao-zhu; Chen, Zhen-hua; Zhang, Yu-lan; Chen, Li-jun

    2015-05-01

    The utilization of organic phosphorus (P) has directly or indirectly improved after exogenous phytase was added to soil. However, the mechanism by which exogenous phytase affected the soil phosphatases (phosphomonoesterase and phosphodiesterase) activities was not clear. The present work was aimed to study red soil, brown soil and cinnamon soil phosphomonoesterase (acid and alkaline) (AcP and AlP) and phosphodiesterase (PD) activities responding to the addition of exogenous phytase (1 g phytase/50 g air dry soil sample) based on the measurements performed via a fluorescence detection method combined with 96 microplates using a TECAN Infinite 200 Multi-Mode Microplate Reader. The results indicated that the acid phosphomonoesterase activity was significantly enhanced in red soil (p≤0. 01), while it was significantly reduced in cinnamon soil; alkaline phosphomonoesterase activity was significantly enhanced in cinnamon soil (p≤ 0. 01), while it was significantly reduced in red soil; phosphodiesterase activity was increased in three soils but it was significantly increased in brown soil (p≤0. 01) after the addition of exogenous phytase. The activities still remained strong after eight days in different soils, which indicated that exogenous phytase addition could be enhance soil phosphatases activities effectively. This effect was not only related to soil properties, such as pH and phosphorus forms, but might also be related to the excreted enzyme amount of the stimulating microorganism. Using fluorescence spectroscopy to study exogenous phytase addition influence on soil phosphatase activities was the first time at home and abroad. Compared with the conventional spectrophotometric method, the fluorescence microplate method is an accurate, fast and simple to use method to determine the relationships among the soil phosphatases activities.

  10. Enhanced Immune Activation Linked to Endotoxemia in HIV-1 Seronegative Men who have Sex with Men

    PubMed Central

    Palmer, Christine D.; Tomassilli, Julia; Sirignano, Michael; Tejeda, Marisol Romero; Arnold, Kelly B.; Che, Denise; Lauffenburger, Douglas A.; Jost, Stephanie; Allen, Todd; Mayer, Kenneth H.; Altfeld, Marcus

    2015-01-01

    Summary This study assessed cellular and soluble markers of immune activation in HIV-1-seronegative men who have sex with men (MSM). MSM immune profiles were characterized by increased expression of CD57 on T cells and endotoxemia. Endotoxin presence was linked to recent high-risk exposure and associated with elevated cytokine levels and decreased CD4/CD8 T cell ratios. Taken together, these data show elevated levels of inflammation linked to periods of endotoxemia resulting in a significantly different immune phenotype in a subset of MSM at high risk of HIV-1 acquisition. PMID:25003719

  11. Probing the active site of a diels-alderase ribozyme by photoaffinity cross-linking.

    PubMed

    Wombacher, Richard; Jäschke, Andres

    2008-07-09

    The active site of a Diels-Alderase ribozyme is located in solution by photoaffinity cross-linking using a productlike azidobenzyl probe. Two key nucleotides are identified that contact the Diels-Alder product in a conformation-dependent fashion. The design of such probes does not require knowledge of the three-dimensional structure of the ribozyme, and the technique yields both static and dynamic structural information. This work establishes photoaffinity cross-linking as an empirical approach that is applied here for the first time to an artificial ribozyme.

  12. Analyses of space environment effects on active fiber optic links orbited aboard the LDEF

    NASA Technical Reports Server (NTRS)

    Taylor, Edward W.; Monarski, T. W.; Berry, J. N.; Sanchez, A. D.; Padden, R. J.; Chapman, S. P.

    1993-01-01

    The results of the 'Preliminary Analysis of WL Experiment no. 701, Space Environment Effects on Operating Fiber Optic Systems,' is correlated with space simulated post retrieval terrestrial studies performed on the M0004 experiment. Temperature cycling measurements were performed on the active optical data links for the purpose of assessing link signal to noise ratio and bit error rate performance some 69 months following the experiment deployment in low Earth orbit. The early results indicate a high correlation between pre-orbit, orbit, and post-orbit functionality of the first known and longest space demonstration of operating fiber optic systems.

  13. Accurate similarity index based on activity and connectivity of node for link prediction

    NASA Astrophysics Data System (ADS)

    Li, Longjie; Qian, Lvjian; Wang, Xiaoping; Luo, Shishun; Chen, Xiaoyun

    2015-05-01

    Recent years have witnessed the increasing of available network data; however, much of those data is incomplete. Link prediction, which can find the missing links of a network, plays an important role in the research and analysis of complex networks. Based on the assumption that two unconnected nodes which are highly similar are very likely to have an interaction, most of the existing algorithms solve the link prediction problem by computing nodes' similarities. The fundamental requirement of those algorithms is accurate and effective similarity indices. In this paper, we propose a new similarity index, namely similarity based on activity and connectivity (SAC), which performs link prediction more accurately. To compute the similarity between two nodes, this index employs the average activity of these two nodes in their common neighborhood and the connectivities between them and their common neighbors. The higher the average activity is and the stronger the connectivities are, the more similar the two nodes are. The proposed index not only commendably distinguishes the contributions of paths but also incorporates the influence of endpoints. Therefore, it can achieve a better predicting result. To verify the performance of SAC, we conduct experiments on 10 real-world networks. Experimental results demonstrate that SAC outperforms the compared baselines.

  14. Effect of Surface-active Additives on Physical Properties of Slurries of Vapor-process Magnesium

    NASA Technical Reports Server (NTRS)

    Pinns, Murray L

    1955-01-01

    The presence of 3 to 5 percent surface-active additive gave the lowest Brookfield apparent viscosity, plastic viscosity, and yield value that were obtained for slurry fuels containing approximately 50 percent vapor-process magnesium in JP-1 fuel. The slurries settled little and were easily remixed. A polyoxyethylene dodecyl alcohol was the most effective of 13 additives tested in reducing the Brookfield apparent viscosity and the yield value of the slurry. The seven most effective additives all had a hydroxyl group plus an ester or polyoxethylene group in the molecule. The densities of some of the slurries were measured.

  15. P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration.

    PubMed

    Hernández-Negrete, Ivette; Carretero-Ortega, Jorge; Rosenfeldt, Hans; Hernández-García, Ricardo; Calderón-Salinas, J Victor; Reyes-Cruz, Guadalupe; Gutkind, J Silvio; Vázquez-Prado, José

    2007-08-10

    Polarized cell migration results from the transduction of extra-cellular cues promoting the activation of Rho GTPases with the intervention of multidomain proteins, including guanine exchange factors. P-Rex1 and P-Rex2 are Rac GEFs connecting Gbetagamma and phosphatidylinositol 3-kinase signaling to Rac activation. Their complex architecture suggests their regulation by protein-protein interactions. Novel mechanisms of activation of Rho GTPases are associated with mammalian target of rapamycin (mTOR), a serine/threonine kinase known as a central regulator of cell growth and proliferation. Recently, two independent multiprotein complexes containing mTOR have been described. mTORC1 links to the classical rapamycin-sensitive pathways relevant for protein synthesis; mTORC2 links to the activation of Rho GTPases and cytoskeletal events via undefined mechanisms. Here we demonstrate that P-Rex1 and P-Rex2 establish, through their tandem DEP domains, interactions with mTOR, suggesting their potential as effectors in the signaling of mTOR to Rac activation and cell migration. This possibility was consistent with the effect of dominant-negative constructs and short hairpin RNA-mediated knockdown of P-Rex1, which decreased mTOR-dependent leucine-induced activation of Rac and cell migration. Rapamycin, a widely used inhibitor of mTOR signaling, did not inhibit Rac activity and cell migration induced by leucine, indicating that P-Rex1, which we found associated to both mTOR complexes, is only active when in the mTORC2 complex. mTORC2 has been described as the catalytic complex that phosphorylates AKT/PKB at Ser-473 and elicits activation of Rho GTPases and cytoskeletal reorganization. Thus, P-Rex1 links mTOR signaling to Rac activation and cell migration.

  16. Dioxygen activation by non-adiabatic oxidative addition to a single metal center [O2 activation by non-adiabatic oxidative addition to a single metal center

    DOE PAGES

    Akturk, Eser S.; Yap, Glenn P. A.; Theopold, Klaus H.

    2015-10-16

    A chromium(I) dinitrogen complex reacts rapidly with O2 to form the mononuclear dioxo complex [TptBu,MeCrV(O)2] (TptBu,Me=hydrotris(3-tert-butyl-5-methylpyrazolyl)borate), whereas the analogous reaction with sulfur stops at the persulfido complex [TptBu,MeCrIII(S2)]. The transformation of the putative peroxo intermediate [TptBu,MeCrIII(O2)] (S=3/2) into [TptBu,MeCrV(O)2] (S=1/2) is spin-forbidden. The minimum-energy crossing point for the two potential energy surfaces has been identified. Finally, although the dinuclear complex [(TptBu,MeCr)2(μ-O)2] exists, mechanistic experiments suggest that O2 activation occurs on a single metal center, by an oxidative addition on the quartet surface followed by crossover to the doublet surface.

  17. HTLV-1 Tax-induced NF{kappa}B activation is independent of Lys-63-linked-type polyubiquitination

    SciTech Connect

    Gohda, Jin; Irisawa, Masato; Tanaka, Yuetsu; Sato, Shintaro; Ohtani, Kiyoshi; Fujisawa, Jun-ichi; Inoue, Jun-ichiro . E-mail: jun-i@ims.u-tokyo.ac.jp

    2007-05-25

    Human T-cell leukemia virus type 1 (HTLV-1) Tax-induced activation of nuclear factor-{kappa}B (NF{kappa}B) is thought to play a critical role in T-cell transformation and onset of adult T-cell leukemia. However, the molecular mechanism of the Tax-induced NF{kappa}B activation remains unknown. One of the mitogen-activated protein kinase kinase kinses (MAP3Ks) members, TAK1, plays a critical role in cytokine-induced activation of NF{kappa}B, which involves lysine 63-linked (K63) polyubiquitination of NEMO, a noncatalytic subunit of the I{kappa}B kinase complex. Here we show that Tax induces K63 polyubiquitination of NEMO. However, TAK1 is dispensable for Tax-induced NF{kappa}B activation, and deubiquitination of the K63 polyubiquitin chain failed to block Tax-induced NF{kappa}B activation. In addition, silencing of other MAP3Ks, including MEKK1, MEKK3, NIK, and TPL-2, did not affect Tax-induced NF{kappa}B activation. These results strongly suggest that unlike cytokine signaling, Tax-induced NF{kappa}B activation does not involve K63 polyubiquitination-mediated MAP3K activation.

  18. Improvement of activated sludge resistance to shock loading by fungal enzyme addition during textile wastewater treatment.

    PubMed

    Manai, Imène; Miladi, Baligh; El Mselmi, Abdellatif; Hamdi, Moktar; Bouallagui, Hassib

    2017-04-01

    The effects of the additions of the fungal enzymatic extract were investigated in relation to the treatment of real textile wastewater (RTW) by the activated sludge process (ASP). The used enzyme cocktail was produced by a new isolated fungal Chaetomium globosum IMA1. The system that was operated with enzyme addition showed a better chemical oxygen demand (COD) removal efficiency (95%) compared to the control system (75%). In addition, the improvement of color removal (OD620) efficiencies was around 15%, when the newly consortium fungal enzymes was added. As the organic loading rate (OLR) increased from 0.33 g to 0.66 g COD L(-1) d(-1), a decrease in the performance of the two reactors was observed by monitoring the quality of treated effluents. However, the ASP working with enzyme addition showed a strong resistance to shock loadings and restored after few days compared to the control system, which was strongly inhibited. In fact, the enzyme addition improved the sludge volume index (SVI) and the activity of microorganisms. A high activity of laccase (300 U.L(-1)) enzyme was observed throughout the decolorization process in the improved system.

  19. Additives increasing antioxidant activity of sesamol in soybean oil at frying temperature

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sesamol has drawn a considerable interest as an alternative to synthetic antioxidants due to its excellent radical scavenging ability at room temperature, low cost and additional health-promoting benefits. However, when it was evaluated for its antioxidant activity in soybean oil at frying temperatu...

  20. Kinetic effect of Pd additions on the hydrogen uptake of chemically activated, ultramicroporous carbon

    SciTech Connect

    Bhat, Vinay V; Contescu, Cristian I; Gallego, Nidia C

    2010-01-01

    The effect of mixing chemically-activated ultramicroporous carbon (UMC) with Pd nanopowder is investigated. Results show that Pd addition doubles the rate of hydrogen uptake, but does not enhance the hydrogen capacity or improve desorption kinetics. The effect of Pd on the rate of hydrogen adsorption supports the occurrence of the hydrogen spillover mechanism in the Pd - UMC system.

  1. Estrogenic activity of phenolic additives determined by an in vitro yeast bioassay.

    PubMed

    Miller, D; Wheals, B B; Beresford, N; Sumpter, J P

    2001-02-01

    We used a recombinant yeast estrogen assay to assess the activity of 73 phenolic additives that are used as sunscreens, preservatives, disinfectants, antioxidants, flavorings, or for perfumery. Thirty-two of these compounds displayed activity: 22 with potencies relative to 17beta-estradiol, ranging from 1/3,000 to < 1/3,000,000, and 10 compounds with an impaired response that could not be directly compared with 17beta-estradiol. Forty-one compounds were inactive. The major criteria for activity appear to be the presence of an unhindered phenolic OH group in a para position and a molecular weight of 140-250 Da.

  2. Activation energies for addition of O/3P/ to simple olefins.

    NASA Technical Reports Server (NTRS)

    Demore, W. B.

    1972-01-01

    Description of relative rate measurements for the addition of O(3P) to C2H4, C2F4, C3H6, and C4H8-1 in liquid argon at 87.5 K. The data strongly indicate that the activation energies for the addition of O(3P) to the double bonds of propylene and butene-1 are identical, probably to within 0.1 kcal/mole. It is very doubtful that differences in pre-exponential factors or other factors such as solvent effects, could invalidate this conclusion. A similar argument holds for the C2H4 and C2F4 reactions. Furthermore, the experiments suggest that the activation energy for addition of O(3P) to the double bond of butene-1 is about 0.1 kcal/mole.

  3. A serendipitous discovery of antifreeze protein-specific activity in C-linked antifreeze glycoprotein analogs.

    PubMed

    Eniade, Adewale; Purushotham, Madhusudhan; Ben, Robert N; Wang, J B; Horwath, Kathleen

    2003-01-01

    Structurally diverse carbon-linked (C-linked) analogs of antifreeze glycoprotein (AFGP) have been prepared via linear or convergent solid phase synthesis. These analogs range in molecular weight from approx 1.5-4.1 KDa and do not possess the beta-D-galactose-1,3-alpha-D-N-acetylgalactosamine carbohydrate moiety or the L-threonine-L-alanine-L-alanine polypeptide backbone native to the AFGP wild-type. Despite these dramatic structural modifications, the 2.7-KDa and 4.1-KDa analogs possess antifreeze protein-specific activity as determined by recrystallization-inhibition (RI) and thermal hysteresis (TH) assays. These analogs are weaker than the wild-type in their activity, but nanoliter osmometry indicates that these compounds are binding to ice and affecting a localized freezing point depression. This is the first example of a C-linked AFGP analog that possesses TH and RI activity and suggests that the rational design and synthesis of chemically and biologically stable AFGP analogs is a feasible and worthwhile endeavor. Given the low degree of TH activity, these compounds may prove useful for the protection of cells during freezing and thawing cycles.

  4. Linking Microbial Activity with Arsenic Fate during Cow Dung Disposal of Arsenic-Bearing Wastes

    NASA Astrophysics Data System (ADS)

    Clancy, T. M.; Reddy, R.; Tan, J.; Hayes, K. F.; Raskin, L.

    2014-12-01

    To address widespread arsenic contamination of drinking water sources numerous technologies have been developed to remove arsenic. All technologies result in the production of an arsenic-bearing waste that must be evaluated and disposed in a manner to limit the potential for environmental release and human exposure. One disposal option that is commonly recommended for areas without access to landfills is the mixing of arsenic-bearing wastes with cow dung. These recommendations are made based on the ability of microorganisms to create volatile arsenic species (including mono-, di-, and tri-methylarsine gases) to be diluted in the atmosphere. However, most studies of environmental microbial communities have found only a small fraction (<0.1 %) of the total arsenic present in soils or rice paddies is released via volatilization. Additionally, past studies often have not monitored arsenic release in the aqueous phase. Two main pathways for microbial arsenic volatilization are known and include methylation of arsenic during methanogenesis and methylation by arsenite S-adenosylmethionine methyltransferase. In this study, we compare the roles of these two pathways in arsenic volatilization and aqueous mobilization through mesocosm experiments with cow dung and arsenic-bearing wastes produced during drinking water treatment in West Bengal, India. Arsenic in gaseous, aqueous, and solid phases was measured. Consistent with previous reports, less than 0.02% of the total arsenic present was volatilized. A much higher amount (~5%) of the total arsenic was mobilized into the liquid phase. Through the application of molecular tools, including 16S rRNA sequencing and quantification of gene transcripts involved in methanogenesis, this study links microbial community activity with arsenic fate in potential disposal environments. These results illustrate that disposal of arsenic-bearing wastes by mixing with cow dung does not achieve its end goal of promoting arsenic volatilization

  5. Differential activation of an identified motor neuron and neuromodulation provide Aplysia's retractor muscle an additional function.

    PubMed

    McManus, Jeffrey M; Lu, Hui; Cullins, Miranda J; Chiel, Hillel J

    2014-08-15

    To survive, animals must use the same peripheral structures to perform a variety of tasks. How does a nervous system employ one muscle to perform multiple functions? We addressed this question through work on the I3 jaw muscle of the marine mollusk Aplysia californica's feeding system. This muscle mediates retraction of Aplysia's food grasper in multiple feeding responses and is innervated by a pool of identified neurons that activate different muscle regions. One I3 motor neuron, B38, is active in the protraction phase, rather than the retraction phase, suggesting the muscle has an additional function. We used intracellular, extracellular, and muscle force recordings in several in vitro preparations as well as recordings of nerve and muscle activity from intact, behaving animals to characterize B38's activation of the muscle and its activity in different behavior types. We show that B38 specifically activates the anterior region of I3 and is specifically recruited during one behavior, swallowing. The function of this protraction-phase jaw muscle contraction is to hold food; thus the I3 muscle has an additional function beyond mediating retraction. We additionally show that B38's typical activity during in vivo swallowing is insufficient to generate force in an unmodulated muscle and that intrinsic and extrinsic modulation shift the force-frequency relationship to allow contraction. Using methods that traverse levels from individual neuron to muscle to intact animal, we show how regional muscle activation, differential motor neuron recruitment, and neuromodulation are key components in Aplysia's generation of multifunctionality.

  6. Carbon–carbon bond activation of cyclobutenones enabled by the addition of chiral organocatalyst to ketone

    PubMed Central

    Li, Bao-Sheng; Wang, Yuhuang; Jin, Zhichao; Zheng, Pengcheng; Ganguly, Rakesh; Chi, Yonggui Robin

    2015-01-01

    The activation of carbon–carbon (C–C) bonds is an effective strategy in building functional molecules. The C–C bond activation is typically accomplished via metal catalysis, with which high levels of enantioselectivity are difficult to achieve due to high reactivity of metal catalysts and the metal-bound intermediates. It remains largely unexplored to use organocatalysis for C–C bond activation. Here we describe an organocatalytic activation of C–C bonds through the addition of an NHC to a ketone moiety that initiates a C–C single bond cleavage as a key step to generate an NHC-bound intermediate for chemo- and stereo-selective reactions. This reaction constitutes an asymmetric functionalization of cyclobutenones using organocatalysts via a C–C bond activation process. Structurally diverse and multicyclic compounds could be obtained with high optical purities via an atom and redox economic process. PMID:25652912

  7. Effect of plasma and carboxylesterase on the stability, mutagenicity, and DNA cross-linking activity of some direct-acting N-nitroso compounds.

    PubMed

    Aukerman, S L; Brundrett, R B; Hilton, J; Hartman, P E

    1983-01-01

    The effects of mouse plasma, human plasma, and purified porcine liver carboxylesterase on nitrosourea, nitrosamide, and nitrosocarbamate chemical stability, mutagenicity, and DNA cross-linking activity were compared. These three classes of N-nitroso compounds are chemically similar but displayed different biological activities and were affected differently by plasma and carboxylesterase. Nitrosourea stability as well as mutagenicity and DNA cross-linking activity were affected negligibly by esterase or plasma. In contrast, nitrosamide and nitrosocarbamate stability, mutagenicity, and DNA cross-linking activity were rapidly decreased in the presence of plasma or carboxylesterase. For example, chemical half-lives were from 10- to 20-fold shorter for the nitrosamides and nitrosocarbamates in the presence of 5% mouse plasma. Similar decreases were seen for mutagenicity and DNA cross-linking activity. Preliminary studies indicated one active plasma component to be an enzyme, possibly an esterase. Additional factors such as sulfhydryls may also participate. Whereas some nitrosoureas are active antitumor agents, the lack of antitumor activity for analogous nitrosamides and nitrosocarbamates may reside predominantly in their rapid in vivo inactivation. These results may help to account for the high in vitro mutagenicity as compared with the low in vivo activities of nitrosamides and nitrosocarbamates.

  8. Interactions between organic additives and active powders in water-based lithium iron phosphate electrode slurries

    NASA Astrophysics Data System (ADS)

    Li, Chia-Chen; Lin, Yu-Sheng

    2012-12-01

    The interactions of organic additives with active powders are investigated and are found to have great influence on the determination of the mixing process for preparing electrode slurries with good dispersion and electrochemical properties of lithium iron phosphate (LiFePO4) electrodes. Based on the analyses of zeta potential, sedimentation, and rheology, it is shown that LiFePO4 prefers to interact with styrene-butadiene rubber (SBR) relative to other organic additives such as sodium carboxymethyl cellulose (SCMC), and thus shows preferential adsorption by SBR, whereas SBR has much lower efficiency than SCMC in dispersing LiFePO4. Therefore, for SCMC to interact with and disperse LiFePO4 before the interaction of LiFePO4 with SBR, it is suggested to mix SCMC with LiFePO4 prior to the addition of SBR during the slurry preparation process. For the electrode prepared via the suggested process, i.e., the sequenced adding process in which SCMC is mixed with active powders prior to the addition of SBR, a much better electrochemical performance is obtained than that of the one prepared via the process referred as the simultaneous adding process, in which mixing of SCMC and SBR with active powders in simultaneous.

  9. Evaluating the additivity of perfluoroalkyl acids in binary combinations on peroxisome proliferator-activated receptor-α activation.

    PubMed

    Wolf, Cynthia J; Rider, Cynthia V; Lau, Christopher; Abbott, Barbara D

    2014-02-28

    Perfluoroalkyl acids (PFAAs) are found globally in the environment, detected in humans and wildlife, and are typically present as mixtures of PFAA congeners. Mechanistic studies have found that responses to PFAAs are mediated in part by PPARα. Our previous studies showed that individual PFAAs activate PPARα transfected into COS-1 cells. The goal of the current study was to determine if binary combinations of perfluorooctanoic acid (PFOA) and another PFAA act in an additive fashion to activate PPARα in the mouse one-hybrid in vitro model. COS-1 cells were transiently transfected with mouse PPARα luciferase reporter construct and exposed to either vehicle control (0.1% DMSO or water), PPARα agonist (WY14643, 10 μM), PFOA at 1-128μM, perfluorononanoic acid (PFNA) at 1-128 μM, perfluorohexanoic acid (PFHxA) at 8-1024 μM, perfluorooctane sulfonate (PFOS) at 4-384 μM or perfluorohexane sulfonate (PFHxS) at 8-2048 μM to generate sigmoidal concentration-response curves. In addition, cells were exposed to binary combinations of PFOA+either PFNA, PFHxA, PFOS or PFHxS in an 8×8 factorial design. The concentration-response data for individual chemicals were fit to sigmoidal curves and analyzed with nonlinear regression to generate EC₅₀s and Hillslopes, which were used in response-addition and concentration-addition models to calculate predicted responses for mixtures in the same plate. All PFOA+PFAA combinations produced concentration-response curves that were closely aligned with the predicted curves for both response addition and concentration addition at low concentrations. However, at higher concentrations of all chemicals, the observed response curves deviated from the predicted models of additivity. We conclude that binary combinations of PFAAs behave additively at the lower concentration ranges in activating PPARα in this in vitro system.

  10. Link direction for link prediction

    NASA Astrophysics Data System (ADS)

    Shang, Ke-ke; Small, Michael; Yan, Wei-sheng

    2017-03-01

    Almost all previous studies on link prediction have focused on using the properties of the network to predict the existence of links between pairs of nodes. Unfortunately, previous methods rarely consider the role of link direction for link prediction. In fact, many real-world complex networks are directed and ignoring the link direction will mean overlooking important information. In this study, we propose a phase-dynamic algorithm of the directed network nodes to analyse the role of link directions and demonstrate that the bi-directional links and the one-directional links have different roles in link prediction and network structure formation. From this, we propose new directional prediction methods and use six real networks to test our algorithms. In real networks, we find that compared to a pair of nodes which are connected by a one-directional link, a pair of nodes which are connected by a bi-directional link always have higher probabilities to connect to the common neighbours with only bi-directional links (or conversely by one-directional links). We suggest that, in the real networks, the bi-directional links will generally be more informative for link prediction and network structure formation. In addition, we propose a new directional randomized algorithm to demonstrate that the direction of the links plays a significant role in link prediction and network structure formation.

  11. Signal transduction-associated and cell activation-linked antigens expressed in human mast cells.

    PubMed

    Valent, Peter; Ghannadan, Minoo; Hauswirth, Alexander W; Schernthaner, Gerit-Holger; Sperr, Wolfgang R; Arock, Michel

    2002-05-01

    Mast cells (MCs) are multifunctional hematopoietic effector cells that produce and release an array of biologically active mediator substances. Growth and functions of MCs are regulated by cytokines, other extracellular factors, surface and cytoplasmic receptors, oncogene products, and a complex network of signal transduction cascades. Key regulators of differentiation of MCs appear to be stem cell factor (SCF) and its tyrosine kinase receptor KIT (c-kit proto-oncogene product=CD117), downstream-acting elements, and the mi transcription factor (MITF). Signaling through KIT is negatively regulated by the signal regulatory protein (SIRP)-alpha (CD172a)-SHP-1-pathway that is disrupted in neoplastic MCs in MC proliferative disorders. Both KIT and FcepsilonRI are involved in MC activation and mediator release. Activation of MCs through FcepsilonRI is associated with increased expression of activation-linked membrane antigens as well as with signaling events involving Lyn and Syk kinases, the phosphatidylinositol-3-kinase-pathway, Ras pathway, and the phospholipase C-protein kinase C pathway. A similar network of signaling is found in SCF-activated MCs. The current article gives an overview on signal transduction-associated and activation-linked antigens expressed in human MCs. Wherever possible the functional implication of signaling pathways and antigen expression are discussed.

  12. Coherent activity between brain regions that code for value is linked to the malleability of human behavior

    PubMed Central

    Cooper, Nicole; Bassett, Danielle S.; Falk, Emily B.

    2017-01-01

    Brain activity in medial prefrontal cortex (MPFC) during exposure to persuasive messages can predict health behavior change. This brain-behavior relationship has been linked to areas of MPFC previously associated with self-related processing; however, the mechanism underlying this relationship is unclear. We explore two components of self-related processing – self-reflection and subjective valuation – and examine coherent activity between relevant networks of brain regions during exposure to health messages encouraging exercise and discouraging sedentary behaviors. We find that objectively logged reductions in sedentary behavior in the following month are linked to functional connectivity within brain regions associated with positive valuation, but not within regions associated with self-reflection on personality traits. Furthermore, functional connectivity between valuation regions contributes additional information compared to average brain activation within single brain regions. These data support an account in which MPFC integrates the value of messages to the self during persuasive health messaging and speak to broader questions of how humans make decisions about how to behave. PMID:28240271

  13. Recognition of protein-linked glycans as a determinant of peptidase activity.

    PubMed

    Noach, Ilit; Ficko-Blean, Elizabeth; Pluvinage, Benjamin; Stuart, Christopher; Jenkins, Meredith L; Brochu, Denis; Buenbrazo, Nakita; Wakarchuk, Warren; Burke, John E; Gilbert, Michel; Boraston, Alisdair B

    2017-01-31

    The vast majority of proteins are posttranslationally altered, with the addition of covalently linked sugars (glycosylation) being one of the most abundant modifications. However, despite the hydrolysis of protein peptide bonds by peptidases being a process essential to all life on Earth, the fundamental details of how peptidases accommodate posttranslational modifications, including glycosylation, has not been addressed. Through biochemical analyses and X-ray crystallographic structures we show that to hydrolyze their substrates, three structurally related metallopeptidases require the specific recognition of O-linked glycan modifications via carbohydrate-specific subsites immediately adjacent to their peptidase catalytic machinery. The three peptidases showed selectivity for different glycans, revealing protein-specific adaptations to particular glycan modifications, yet always cleaved the peptide bond immediately preceding the glycosylated residue. This insight builds upon the paradigm of how peptidases recognize substrates and provides a molecular understanding of glycoprotein degradation.

  14. Links between osteoarthritis and diabetes: implications for management from a physical activity perspective.

    PubMed

    Piva, Sara R; Susko, Allyn M; Khoja, Samannaaz S; Josbeno, Deborah A; Fitzgerald, G Kelley; Toledo, Frederico G S

    2015-02-01

    Osteoarthritis (OA) and type 2 diabetes mellitus (T2DM) often coexist in older adults. Those with T2DM are more susceptible to developing arthritis, which has been traditionally attributed to common risk factors, namely, age and obesity. Alterations in lipid metabolism and hyperglycemia might directly impact cartilage health and subchondral bone, contributing to the development/progression of OA. Adequate management of older persons with both conditions benefits from a comprehensive understanding of the associated risk factors. We discuss common risk factors and emerging links between OA and T2DM, emphasizing the importance of physical activity and the implications of safe and effective physical activity.

  15. Activation of the p75 neurotrophin receptor through conformational rearrangement of disulphide-linked receptor dimers

    PubMed Central

    Vilar, Marçal; Charalampopoulos, Ioannis; Kenchappa, Rajappa S.; Simi, Anastasia; Karaca, Esra; Reversi, Alessandra; Choi, Soyoung; Bothwell, Mark; Mingarro, Ismael; Friedman, Wilma J.; Schiavo, Giampietro; Bastiaens, Philippe I. H.; Verveer, Peter J.; Carter, Bruce D.; Ibáñez, Carlos F.

    2010-01-01

    SUMMARY Ligand-mediated dimerization has emerged as a universal mechanism of growth factor receptor activation. Recent structural studies have shown that neurotrophins interact with dimers of the p75 neurotrophin receptor (p75NTR), but the actual mechanism of receptor activation has remained elusive. Here we show that p75NTR forms disulphide-linked dimers independently of neurotrophin binding through the highly conserved Cys257 in its transmembrane domain. Mutation of Cys257 abolished neurotrophin-dependent receptor activity but did not affect downstream signaling by the p75NTR/NgR/Lingo-1 complex in response to MAG, indicating the existence of distinct, ligand-specific activation mechanisms for p75NTR. FRET experiments revealed a close association of p75NTR intracellular domains that was transiently disrupted by conformational changes induced upon NGF binding. Although mutation of Cys257 did not alter the oligomeric state of p75NTR, the mutant receptor was no longer able to propagate conformational changes to the cytoplasmic domain upon ligand binding. We propose that neurotrophins activate p75NTR by a novel mechanism involving rearrangement of disulphide-linked receptor subunits. PMID:19376068

  16. Optical properties and photocatalytic activities of tungsten oxide (WO3) with platinum co-catalyst addition

    NASA Astrophysics Data System (ADS)

    Widiyandari, Hendri; Firdaus, Iqbal; Kadarisman, Vincencius Gunawan Slamet; Purwanto, Agus

    2016-02-01

    This research reported the optical properties and photocatalytic activities of tungsten oxide with platinum co-catalyst addition (WO3/Pt) film. The platinum was deposited on the surface of WO3 particle using photo deposition method, while the film formation of WO3/Pt on the glass substrate was prepared using spray deposition method. The addition of Pt of 0, 1, 2, and 4 wt.% resulted that the energy band gap value of the films were shifted to 2.840, 2.752, 2.623 and 2.507 eV, respectively. The as-prepared films were tested for methylene blue (MB) dye photo-degradation using the LED (light emitting diode) lamp as a visible domestic source light. The enhancement of photocatalytic activity was observed after the addition of Pt as a co-catalyst. The degradation kinetics analysis of the photo-catalyst showed that the Pt addition resulted increasing of photo-catalysis reaction rate constant, k.

  17. Autoinducer-2-like activity associated with foods and its interaction with food additives.

    PubMed

    Lu, Lingeng; Hume, Michael E; Pillai, Suresh D

    2004-07-01

    The autoinducer-2 (AI-2) molecule produced by bacteria as part of quorum sensing is considered to be a universal inducer signal in bacteria because it reportedly influences gene expression in a variety of both gram-negative and gram-positive bacteria. The objective of this study was to determine whether selected fresh produce and processed foods have AI-2-like activity and whether specific food additives can act as AI-2 mimics and result in AI-2-like activity. The luminescence-based response of the reporter strain Vibrio harveyi BB170 was used as the basis for determining AI-2 activity in the selected foods and food ingredients. Maximum AI-2 activity was seen on the frozen fish sample (203-fold, compared with the negative control) followed by tomato, cantaloupe, carrots, tofu, and milk samples. Interestingly, some samples were capable of inhibiting AI-2 activity. Turkey patties showed the highest inhibition (99.8% compared with the positive control) followed by chicken breast (97.5%), homemade cheeses (93.7%), beef steak (90.6%), and beef patties (84.4%). AI-2 activity was almost totally inhibited by sodium propionate, whereas sodium benzoate caused 93.3% inhibition, compared with 75% inhibition by sodium acetate. Sodium nitrate did not have any appreciable effect, even at 200 ppm. Understanding the relationships that exist between AI-2 activity on foods and the ecology of pathogens and food spoilage bacteria on foods could yield clues about factors controlling food spoilage and pathogen virulence.

  18. The additionally glycosylated variant of human sex hormone-binding globulin (SHBG) is linked to estrogen-dependence of breast cancer.

    PubMed

    Becchis, M; Frairia, R; Ferrera, P; Fazzari, A; Ondei, S; Alfarano, A; Coluccia, C; Biglia, N; Sismondi, P; Fortunati, N

    1999-03-01

    Sex Hormone-Binding Globulin (SHBG), the plasma carrier for androgens and estradiol, inhibits the estradiol-induced proliferation of breast cancer cells through its membrane receptor, cAMP, and PKA. In addition, the SHBG membrane receptor is preferentially expressed in estrogen-dependent (ER+/PR+) breast cancers which are also characterized by a lower proliferative rate than tumors negative for the SHBG receptor. A variant SHBG with a point mutation in exon 8, causing an aminoacid substitution (Asp 327-->Asn) and thus, the introduction of an additional N-glycosylation site, has been reported. In this work, the distribution of the SHBG variant was studied in 255 breast cancer patients, 32 benign mammary disease patients, and 120 healthy women. The presence of the SHBG mutation was evaluated with PCR amplification of SHBG exon 8 and Hinf I restriction fragment length polymorphism (RFLP) procedure. This technique allowed us to identify 54 SHBG variants (53 W/v and 1 v/v) in breast cancer patients (21.2%), 5 variants (4 W/v and 1 v/v) in benign mammary disease patients (15.6%), and 14 variants (W/v) in the control group (11.6%). The results of PCR and RFLP were confirmed both by nucleotide sequence of SHBG exon 8 and western blot of the plasma SHBG. No differences in the mean plasma level of the protein were observed in the three populations. The frequency of the SHBG variant was significantly higher in ER+/PR+ tumors and in tumors diagnosed in patients over 50 years of age than in the control group. This observation suggests the existence of a close link between the estrogen-dependence of breast cancer and the additionally glycosylated SHBG, further supporting a critical role of the protein in the neoplasm.

  19. Synergistic Enhancement of Cellobiohydrolase Performance on Pretreated Corn Stover by Addition of Xylanase and Esterase Activities

    SciTech Connect

    Selig, M. J.; Knoshaug E. P.; Adney, W. S.; Himmel, M. E.; Decker, S. R.

    2007-11-01

    Significant increases in the depolymerization of corn stover cellulose by cellobiohydrolase I (Cel7A) from Trichoderma reesei were observed using small quantities of non-cellulolytic cell wall-degrading enzymes. Purified endoxylanase (XynA), ferulic acid esterase (FaeA), and acetyl xylan esterase (Axe1) all enhanced Cel7A performance on corn stover subjected to hot water pretreatment. In all cases, the addition of these activities improved the effectiveness of the enzymatic hydrolysis in terms of the quantity of cellulose converted per milligram of total protein. Improvement in cellobiose release by the addition of the non-cellulolytic enzymes ranged from a 13-84% increase over Cel7A alone. The most effective combinations included the addition of both XynA and Axe1, which synergistically enhance xylan conversions resulting in additional synergistic improvements in glucan conversion. Additionally, we note a direct relationship between enzymatic xylan removal in the presence of XynA and the enhancement of cellulose hydrolysis by Cel7A.

  20. High temperature hydrogen sulfide adsorption on activated carbon - I. Effects of gas composition and metal addition

    USGS Publications Warehouse

    Cal, M.P.; Strickler, B.W.; Lizzio, A.A.

    2000-01-01

    Various types of activated carbon sorbents were evaluated for their ability to remove H2S from a simulated coal gas stream at a temperature of 550 ??C. The ability of activated carbon to remove H2S at elevated temperature was examined as a function of carbon surface chemistry (oxidation, thermal desorption, and metal addition), and gas composition. A sorbent prepared by steam activation, HNO3 oxidation and impregnated with Zn, and tested in a gas stream containing 0.5% H2S, 50% CO2 and 49.5% N2, had the greatest H2S adsorption capacity. Addition of H2, CO, and H2O to the inlet gas stream reduced H2S breakthrough time and H2S adsorption capacity. A Zn impregnated activated carbon, when tested using a simulated coal gas containing 0.5% H2S, 49.5% N2, 13% H2, 8.5% H2O, 21% CO, and 7.5% CO2, had a breakthrough time of 75 min, which was less than 25 percent of the length of breakthrough for screening experiments performed with a simplified gas mixture of 0.5% H2S, 50% CO2, and 49.5% N2.

  1. Myosin III-mediated cross-linking and stimulation of actin bundling activity of Espin.

    PubMed

    Liu, Haiyang; Li, Jianchao; Raval, Manmeet H; Yao, Ningning; Deng, Xiaoying; Lu, Qing; Nie, Si; Feng, Wei; Wan, Jun; Yengo, Christopher M; Liu, Wei; Zhang, Mingjie

    2016-01-19

    Class III myosins (Myo3) and actin-bundling protein Espin play critical roles in regulating the development and maintenance of stereocilia in vertebrate hair cells, and their defects cause hereditary hearing impairments. Myo3 interacts with Espin1 through its tail homology I motif (THDI), however it is not clear how Myo3 specifically acts through Espin1 to regulate the actin bundle assembly and stabilization. Here we discover that Myo3 THDI contains a pair of repeat sequences capable of independently and strongly binding to the ankyrin repeats of Espin1, revealing an unexpected Myo3-mediated cross-linking mechanism of Espin1. The structures of Myo3 in complex with Espin1 not only elucidate the mechanism of the binding, but also reveal a Myo3-induced release of Espin1 auto-inhibition mechanism. We also provide evidence that Myo3-mediated cross-linking can further promote actin fiber bundling activity of Espin1.

  2. Acetylation of glycerol to biofuel additives over sulfated activated carbon catalyst.

    PubMed

    Khayoon, M S; Hameed, B H

    2011-10-01

    Oxygenated fuel additives can be produced by acetylation of glycerol. A 91% glycerol conversion with a selectivity of 38%, 28% and 34% for mono-, di- and triacetyl glyceride, respectively, was achieved at 120 °C and 3 h of reaction time in the presence of a catalyst derived from activated carbon (AC) treated with sulfuric acid at 85 °C for 4h to introduce acidic functionalities to its surface. The unique catalytic activity of the catalyst, AC-SA5, was attributed to the presence of sulfur containing functional groups on the AC surface, which enhanced the surface interaction between the glycerol molecule and acyl group of the acetic acid. The catalyst was reused in up to four consecutive batch runs and no significant decline of its initial activity was observed. The conversion and selectivity variation during the acetylation is attributed to the reaction time, reaction temperature, catalyst loading and glycerol to acetic acid molar ratio.

  3. Controlling the corrosion and cathodic activation of magnesium via microalloying additions of Ge

    NASA Astrophysics Data System (ADS)

    Liu, R. L.; Hurley, M. F.; Kvryan, A.; Williams, G.; Scully, J. R.; Birbilis, N.

    2016-06-01

    The evolution of corrosion morphology and kinetics for magnesium (Mg) have been demonstrated to be influenced by cathodic activation, which implies that the rate of the cathodic partial reaction is enhanced as a result of anodic dissolution. This phenomenon was recently demonstrated to be moderated by the use of arsenic (As) alloying as a poison for the cathodic reaction, leading to significantly improved corrosion resistance. The pursuit of alternatives to toxic As is important as a means to imparting a technologically safe and effective corrosion control method for Mg (and its alloys). In this work, Mg was microalloyed with germanium (Ge), with the aim of improving corrosion resistance by retarding cathodic activation. Based on a combined analysis herein, we report that Ge is potent in supressing the cathodic hydrogen evolution reaction (reduction of water) upon Mg, improving corrosion resistance. With the addition of Ge, cathodic activation of Mg subject to cyclic polarisation was also hindered, with beneficial implications for future Mg electrodes.

  4. Controlling the corrosion and cathodic activation of magnesium via microalloying additions of Ge.

    PubMed

    Liu, R L; Hurley, M F; Kvryan, A; Williams, G; Scully, J R; Birbilis, N

    2016-06-28

    The evolution of corrosion morphology and kinetics for magnesium (Mg) have been demonstrated to be influenced by cathodic activation, which implies that the rate of the cathodic partial reaction is enhanced as a result of anodic dissolution. This phenomenon was recently demonstrated to be moderated by the use of arsenic (As) alloying as a poison for the cathodic reaction, leading to significantly improved corrosion resistance. The pursuit of alternatives to toxic As is important as a means to imparting a technologically safe and effective corrosion control method for Mg (and its alloys). In this work, Mg was microalloyed with germanium (Ge), with the aim of improving corrosion resistance by retarding cathodic activation. Based on a combined analysis herein, we report that Ge is potent in supressing the cathodic hydrogen evolution reaction (reduction of water) upon Mg, improving corrosion resistance. With the addition of Ge, cathodic activation of Mg subject to cyclic polarisation was also hindered, with beneficial implications for future Mg electrodes.

  5. Forging Links.

    ERIC Educational Resources Information Center

    Stewig, John Warren

    Blacksmiths and their craft have changed with the times, and as times change for teachers, they too should be forgers of links. Teacher-to-teacher links should extend beyond the faculty lounge to support systems and active groups of individuals concerned about each other. Another personal link can be made by developing a grade level, system-wide…

  6. Giving meaning to measure: linking self-reported fatigue and function to performance of everyday activities.

    PubMed

    Mallinson, Trudy; Cella, David; Cashy, John; Holzner, Bernhard

    2006-03-01

    Fatigue, a common symptom of cancer patients, particularly those on active treatment, is generally evaluated using self-report methods, yet it remains unclear how self-reported fatigue scores relate to performance of daily activities. This study examines the relationships among self-reported and performance-based measures of function in patients receiving chemotherapy (CT) to link self-reported fatigue measures to self-report and performance-based measures of function. Self-reported fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and self-reported physical function using the physical function 10 subscale of the Short Form 36 (SF-36) (PF-10) were measured in 64 patients within 2 weeks of beginning CT (n=64) and after three cycles of CT (n=48). Motor and cognitive functions were captured using five self-reported and seven observed-performance measures at each time point. Significant correlations between self-reported and observed measures ranged from 0.30 to 0.71. Self-reported fatigue correlated (0.30-0.45) with performance-based function. FACIT-F scores in the range of 30 and below and PF-10 scores in the range of 50 and below were related to an increased difficulty performing everyday activities. Observed measures of physical performance correlate moderately with self-reported fatigue and self-reported physical function. These relationships enable one to begin linking fatigue scores directly to a person's ability to perform everyday activities.

  7. Additive effects on the improvement of insecticidal activity: Design, synthesis, and insecticidal activity of novel pymetrozine derivatives.

    PubMed

    Yang, Yan; Liu, Yuxiu; Song, Hongjian; Li, Yongqiang; Wang, Qingmin

    2016-02-01

    A series of new pymetrozine analogues containing both methyl on the imine carbon and phenoxy group at the pyridine ring were designed and synthesized. Their insecticidal activities against bean aphid (Aphis craccivora), mosquito larvae (Culex pipiens pallens), cotton bollworm (Helicoverpa armigera), corn borer (Ostrinia nubilalis) and oriental armyworm (Mythimna separata) were evaluated. The results of bioassays indicated that most of the target compounds showed good insecticidal activity against bean aphid; especially, IIIf (80%) and IIIl (80%) exhibited higher aphicidal activity than pymetrozine (30%) at 5mg/kg, and the two compounds still showed 20% and 30% mortality at 2.5mg/kg, respectively, whereas pymetrozine displayed no activity at the same concentration. These compounds exhibited a completely different structure-activity relationship to that of known pymetrozine derivatives, in which it is thought introducing alkyl group on the imine carbon could be detrimental to the activities. Our new result suggested that the methyl on the imine carbon and phenoxy group at the pyridine ring of phenoxy group may play additive effects on the improvement of aphicidal activity. Besides this, compound IIIs, containing an allyl at the para position of phenoxy group, exhibited excellent insecticidal activity against mosquito larvae, lepidoptera pests cotton bollworm, corn borer and oriental armyworm.

  8. Increased activity of unlinked Zika virus NS2B/NS3 protease compared to linked Zika virus protease.

    PubMed

    Kuiper, Benjamin D; Slater, Kristin; Spellmon, Nicholas; Holcomb, Joshua; Medapureddy, Prasanna; Muzzarelli, Kendall M; Yang, Zhe; Ovadia, Reuben; Amblard, Franck; Kovari, Iulia A; Schinazi, Raymond F; Kovari, Ladislau C

    2017-03-22

    Zika virus (ZIKV) is a flavivirus spread by daytime-active Aedes spp. mosquitoes such as A. aegypti and A. albopictus. Previously thought to be a mild infection, the latest ZIKV outbreak in the Americas is causally associated with more severe symptoms as well as severe birth defects, such as microcephaly. Currently no vaccine or antiviral exists. However, recent progress has demonstrated the viral NS2B/NS3 protease may be a suitable target for the development of small-molecule antiviral agents. To better understand the ZIKV protease, we expressed, purified, and characterized unlinked and linked NS2B/NS3 protease corresponding to an isolate from the recent outbreak in Puerto Rico. Unlinked ZIKV protease is more active and binds substrate with greater affinity than linked ZIKV protease. Therefore, we propose that unlinked ZIKV protease be used when evaluating or designing ZIKV protease inhibitors. Additionally, potent inhibitors of related viral proteases, like West Nile Virus and Dengue virus, may serve as advanced starting points to identify and develop ZIKV protease inhibitors.

  9. Metal active site elasticity linked to activation of homocysteine in methionine synthases

    SciTech Connect

    Koutmos, Markos; Pejchal, Robert; Bomer, Theresa M.; Matthews, Rowena G.; Smith, Janet L.; Ludwig, Martha L.

    2008-04-02

    Enzymes possessing catalytic zinc centers perform a variety of fundamental processes in nature, including methyl transfer to thiols. Cobalamin-independent (MetE) and cobalamin-dependent (MetH) methionine synthases are two such enzyme families. Although they perform the same net reaction, transfer of a methyl group from methyltetrahydrofolate to homocysteine (Hcy) to form methionine, they display markedly different catalytic strategies, modular organization, and active site zinc centers. Here we report crystal structures of zinc-replete MetE and MetH, both in the presence and absence of Hcy. Structural investigation of the catalytic zinc sites of these two methyltransferases reveals an unexpected inversion of zinc geometry upon binding of Hcy and displacement of an endogenous ligand in both enzymes. In both cases a significant movement of the zinc relative to the protein scaffold accompanies inversion. These structures provide new information on the activation of thiols by zinc-containing enzymes and have led us to propose a paradigm for the mechanism of action of the catalytic zinc sites in these and related methyltransferases. Specifically, zinc is mobile in the active sites of MetE and MetH, and its dynamic nature helps facilitate the active site conformational changes necessary for thiol activation and methyl transfer.

  10. PCB bioavailability control in Lumbriculus variegatus through different modes of activated carbon addition to sediments

    SciTech Connect

    Xueli Sun; Upal Ghosh

    2007-07-01

    PCB bioavailability to a freshwater oligochaete (Lumbriculus variegatus) was studied using sediments from a PCB-impacted river that was treated with different modes of granular activated carbon (GAC) addition. The GAC used was bituminous coal-based type TOP. For sediment treated with 2.6% GAC and mixed for 2 min prior to L. variegatus addition, the reduction in total PCB biouptake was 70% for 75-300 {mu}m size carbon, and 92% for the 45-180 {mu}m size carbon. For the case where the GAC was placed as a thin layer on top of the sediments without mixing, the reduction in total PCB uptake was 70%. PCB biouptake kinetics study using treated and untreated sediment showed that the maximum PCB uptake in tissue was achieved at 28 days and decreased after that time. Although the absolute uptake of PCB changed over time, the percent reduction in total PCB uptake upon GAC amendment remained constant after the first few days. Our results indicated that PCB bioavailability was reduced upon the addition and little or no mixing of GAC into sediments. PCB aqueous equilibrium concentration and desorption rates were greatly reduced after GAC amendment, indicating reductions in the two primary mechanisms of PCB bioavailability in sediments: chemical activity and chemical accessibility. 29 refs., 5 figs., 1 tab.

  11. PCB bioavailability control in Lumbriculus variegatus through different modes of activated carbon addition to sediments.

    PubMed

    Sun, Xueli; Ghosh, Upal

    2007-07-01

    PCB bioavailability to a freshwater oligochaete (Lumbriculus variegatus) was studied using sediments from a PCB-impacted river that was treated with different modes of granular activated carbon (GAC) addition. For sedimenttreated with 2.6% GAC and mixed for 2 min prior to L. variegatus addition, the reduction in total PCB biouptake was 70% for 75-300 microm size carbon, and 92% for the 45-180 microm size carbon. For the case where the GAC was placed as a thin layer on top of the sediments without mixing, the reduction in total PCB uptake was 70%. PCB biouptake kinetics study using treated and untreated sediment showed that the maximum PCB uptake in tissue was achieved at 28 days and decreased after that time. Although the absolute uptake of PCB changed over time, the percent reduction in total PCB uptake upon GAC amendment remained constant after the first few days. Our results indicated that PCB bioavailability was reduced upon the addition and little or no mixing of GAC into sediments. PCB aqueous equilibrium concentration and desorption rates were greatly reduced after GAC amendment, indicating reductions in the two primary mechanisms of PCB bioavailability in sediments: chemical activity and chemical accessibility.

  12. Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library

    PubMed Central

    Feng, Jie; Weitner, Megan; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Zhang, Ying

    2015-01-01

    Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics) used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV), thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin), and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy production, and

  13. [Physiologic and molecular mechanisms linking physical activity to cancer risk and progression].

    PubMed

    Ulrich, C M; Wiskemann, J; Steindorf, K

    2012-01-01

    Physical activity is associated with a reduced risk of colon, breast, endometrial, lung, and pancreatic cancer. Evidence for mediating molecular mechanisms from experimental studies substantially strengthens the causal inference for this relationship. Randomized controlled trials indicate that exercise affects metabolic profiles, including hormone levels (estrogen, insulin signaling), inflammation (e.g., C-reactive protein), and adipokine concentrations (e.g., leptin). The size of the effect depends frequently on concurrent changes in body composition. There is also initial evidence for effects on immune function, oxidative stress, and possibly DNA repair capacity. Finally, outdoor physical activity can directly increase 25(OH)-vitamin D levels, providing another potential mechanism for linking physical activity to cancer risk. Randomized controlled studies with biomarker measurements are essential to increase evidence for causality and to identify the most effective intervention strategies and pharmacologic targets.

  14. Linking morphology with activity through the lifetime of pretreated PtNi nanostructured thin film catalysts

    SciTech Connect

    Cullen, David A.; Lopez-Haro, Miguel; Bayle-Guillemaud, Pascale; Debe, Mark; Steinbach, Andrew J.; Guetaz, L.

    2015-01-01

    In this study, the nanoscale morphology of highly active Pt3Ni7 nanostructured thin film fuel cell catalysts is linked with catalyst surface area and activity following catalyst pretreatments, conditioning and potential cycling. The significant role of fuel cell conditioning on the structure and composition of these extended surface catalysts is demonstrated by high resolution imaging, elemental mapping and tomography. The dissolution of Ni during fuel cell conditioning leads to highly complex, porous structures which were visualized in 3D by electron tomography. Quantification of the rendered surfaces following catalyst pretreatment, conditioning, and cycling shows the important role pore structure plays in surface area, activity, and durability.

  15. Linking morphology with activity through the lifetime of pretreated PtNi nanostructured thin film catalysts

    DOE PAGES

    Cullen, David A.; Lopez-Haro, Miguel; Bayle-Guillemaud, Pascale; ...

    2015-01-01

    In this study, the nanoscale morphology of highly active Pt3Ni7 nanostructured thin film fuel cell catalysts is linked with catalyst surface area and activity following catalyst pretreatments, conditioning and potential cycling. The significant role of fuel cell conditioning on the structure and composition of these extended surface catalysts is demonstrated by high resolution imaging, elemental mapping and tomography. The dissolution of Ni during fuel cell conditioning leads to highly complex, porous structures which were visualized in 3D by electron tomography. Quantification of the rendered surfaces following catalyst pretreatment, conditioning, and cycling shows the important role pore structure plays in surfacemore » area, activity, and durability.« less

  16. Artificial Warming and Rain Addition Increase Phenol Oxidase Activity in Arctic Soils

    NASA Astrophysics Data System (ADS)

    Kang, H.; Seo, J.; Jang, I.; Lee, Y. K.

    2014-12-01

    Artic tundra is one of the largest carbon stocks, of which amount is estimated up to 1,600 Pg. Global climate change models predict surface temperature rise and higher precipitation during summer in Arctic regions, raising concerns about faster decomposition of organic carbon and consequent releases of CO2, CH4 and DOC. Microorganisms are directly involved in decomposition process by releasing various extracellular enzymes. In particular, phenol oxidase was noted to play a key role because it is related to dynamics of highly recalcitrant carbon, which often represents a rate-limiting step of overall decomposition. In this study, we monitored phenol oxidase activity, hydrolases (β-glucosidase, cellobiohydrolase, N-acetylglucosaminidase and aminopeptidase), microbial abundance (qPCR) and chemical properties (δ13C and δ15N signatures) of tundra soils exposed to artificial warming and rain addition, by employing a passive chamber method in Cambridge Bay, Canada. Warming and rain addition combinedly increased phenol oxidase activity while no such changes were discernible for other hydrolases. Stable isotope signature indicates that warming induced water stress to the ecosystem and that nitrogen availability may be enhanced, which is partially responsible for the changes in enzyme activities. A short-term warming (2 years) may not accelerate mineralization of easily decomposable carbon, but may affect phenol oxidase which has the longer-term influence on recalcitrant carbon.

  17. Brr2 plays a role in spliceosomal activation in addition to U4/U6 unwinding.

    PubMed

    Zhang, Lingdi; Li, Xueni; Hill, Ryan C; Qiu, Yan; Zhang, Wenzheng; Hansen, Kirk C; Zhao, Rui

    2015-03-31

    Brr2 is a DExD/H-box RNA helicase that is responsible for U4/U6 unwinding, a critical step in spliceosomal activation. Brr2 is a large protein (∼250 kD) that consists of an N-terminal domain (∼500 residues) with unknown function and two Hel308-like modules that are responsible for RNA unwinding. Here we demonstrate that removal of the entire N-terminal domain is lethal to Saccharomyces cerevisiae and deletion of the N-terminal 120 residues leads to splicing defects and severely impaired growth. This N-terminal truncation does not significantly affect Brr2's helicase activity. Brr2-Δ120 can be successfully assembled into the tri-snRNP (albeit at a lower level than the WT Brr2) and the spliceosomal B complex. However, the truncation significantly impairs spliceosomal activation, leading to a dramatic reduction of U5, U6 snRNAs and accumulation of U1 snRNA in the B(act) complex. The N-terminal domain of Brr2 does not seem to be directly involved in regulating U1/5'ss unwinding. Instead, the N-terminal domain seems to be critical for retaining U5 and U6 snRNPs during/after spliceosomal activation through its interaction with snRNAs and possibly other spliceosomal proteins, revealing a new role of Brr2 in spliceosomal activation in addition to U4/U6 unwinding.

  18. The inactive-active phase transition in the noisy additive (exclusive-or) probabilistic cellular automaton

    NASA Astrophysics Data System (ADS)

    Mendonça, J. Ricardo G.

    2016-07-01

    We investigate the inactive-active phase transition in an array of additive (exclusive-or) cellular automata (CA) under noise. The model is closely related with the Domany-Kinzel (DK) probabilistic cellular automaton (PCA), for which there are rigorous as well as numerical estimates on the transition probabilities. Here, we characterize the critical behavior of the noisy additive cellular automaton by mean field analysis and finite-size scaling and show that its phase transition belongs to the directed percolation universality class of critical behavior. As a by-product of our analysis, we argue that the critical behavior of the noisy elementary CA 90 and 102 (in Wolfram’s enumeration scheme) must be the same. We also perform an empirical investigation of the mean field equations to assess their quality and find that away from the critical point (but not necessarily very far away) the mean field approximations provide a reasonably good description of the dynamics of the PCA.

  19. Synthesis and Antimicrobial Activity of Some Novel Cross-Linked Chitosan Hydrogels

    PubMed Central

    Mohamed, Nadia Ahmed; Fahmy, Mona Mohamed

    2012-01-01

    Four novel hydrogels based on chitosan were synthesized via a cross-linking reaction of chitosan with different concentrations of oxalyl bis 4-(2,5-dioxo-2H-pyrrol- 1(5H)-yl)benzamide. Their structures were confirmed by fourier transform infrared X-ray (FTIR), scanning electron microscopy (SEM) and X-ray diffraction. The antimicrobial activities of the hydrogels against two crop-threatening pathogenic fungi namely: Aspergillus fumigatus (A. fumigatus, RCMBA 06002), and Aspergillus niger (A. niger, RCMBA 06106), and five bacterial species namely: Bacillis subtilis (B. subtilis, RCMBA 6005), Staphylococcus aureus (S. aureus, RCMBA 2004), Streptococcus pneumoniae (S. pneumonia, RCMB 000101) as Gram positive bacteria, and Salmonella typhimurium (S. typhimurium, RCMB 000104), and Escherichia coli (E. coli, RCMBA 5003) as Gram negative bacteria have been investigated. The prepared hydrogels showed much higher antimicrobial activities than that of the parent chitosan. The hydrogels were more potent in case of Gram-positive bacteria than Gram-negative bacteria. Increasing the degree of cross-linking in the hydrogels resulted in a weaker antimicrobial activity. PMID:23109847

  20. Time with friends and physical activity as mechanisms linking obesity and television viewing among youth

    PubMed Central

    2015-01-01

    Background Though bivariate relationships between childhood obesity, physical activity, friendships and television viewing are well documented, empirical assessment of the extent to which links between obesity and television may be mediated by these factors is scarce. This study examines the possibility that time with friends and physical activity are potential mechanisms linking overweight/obesity to television viewing in youth. Methods Data were drawn from children ages 10-18 years old (M = 13.81, SD = 2.55) participating in the 2002 wave of Child Development Supplement (CDS) to the Panel Study of Income Dynamics (PSID) (n = 1,545). Data were collected both directly and via self-report from children and their parents. Path analysis was employed to examine a model whereby the relationships between youth overweight/obesity and television viewing were mediated by time spent with friends and moderate-to-vigorous physical activity (MVPA). Results Overweight/obesity was directly related to less time spent with friends, but not to MVPA. Time spent with friends was directly and positively related to MVPA, and directly and negatively related to time spent watching television without friends. In turn, MVPA was directly and negatively related to watching television without friends. There were significant indirect effects of both overweight/obesity and time with friends on television viewing through MVPA, and of overweight/obesity on MVPA through time with friends. Net of any indirect effects, the direct effect of overweight/obesity on television viewing remained. The final model fit the data extremely well (χ2 = 5.77, df = 5, p<0.0001, RMSEA = 0.01, CFI = 0.99, TLI =0.99). Conclusions We found good evidence that the positive relationships between time with friends and physical activity are important mediators of links between overweight/obesity and television viewing in youth. These findings highlight the importance of moving from examinations of bivariate relationships

  1. Scheduling Link Activation in Multihop Radio Networks by Means of Hopfield Neural Network Techniques

    DTIC Science & Technology

    1991-09-03

    CDMA or non-spread-spectrum systems. Sequence Conflicts The sequential schedling requirement is a further restriction of the problem. We declare that...the source node. Thus, overall, we declare :he occurrence of a scheduling conflict if there is a primary conflict, or if there is a sequence conflict...we declare link 1,1 ineligible for activation in slot 3, and enter an "i" in cell 1,1,3. 124 113 1O w ’. i i .. .. . 1 SNeuron representingi the

  2. Active force generation in cross-linked filament bundles without motor proteins.

    PubMed

    Walcott, Sam; Sun, Sean X

    2010-11-01

    Cytoskeletal filaments often interact laterally through cross-linking proteins, contributing to passive cellular viscoelasticity and, perhaps surprisingly, active force generation. We present a theory, based on the formation and rupture of cross-linker bonds, that relates molecular properties of those interactions to the macroscale mechanics of filament bundles. Computing the force-velocity relation for such a bundle, we demonstrate significant contractile forces in the absence of molecular motors. This theory provides insight into cytokinesis, cytoskeletal mechanics, and stress-fiber contraction.

  3. Optimization of membrane bioreactors by the addition of powdered activated carbon.

    PubMed

    Ng, Choon Aun; Sun, Darren; Bashir, Mohammed J K; Wai, Soon Han; Wong, Ling Yong; Nisar, Humaira; Wu, Bing; Fane, Anthony G

    2013-06-01

    It was found that with replenishment, powdered activated carbon (PAC) in the membrane bioreactor (MBR) would develop biologically activated carbon (BAC) which could enhance filtration performance of a conventional MBR. This paper addresses two issues (i) effect of PAC size on MBR (BAC) performance; and (ii) effect of sludge retention time (SRT) on the MBR performance with and without PAC. To interpret the trends, particle/floc size, concentration of mixed liquor suspended solid (MLSS), total organic carbon (TOC), short-term filtration properties and transmembrane pressure (TMP) versus time are measured. The results showed improved fouling control with fine, rather than coarse, PAC provided the flux did not exceed the deposition flux for the fine PAC. Without PAC, the longer SRT operation gave lower fouling at modest fluxes. With PAC addition, the shorter SRT gave better fouling control, possibly due to greater replenishment of the fresh PAC.

  4. Rostral anterior cingulate activity generates posterior versus anterior theta activity linked to agentic extraversion.

    PubMed

    Chavanon, Mira-Lynn; Wacker, Jan; Stemmler, Gerhard

    2011-06-01

    Recent research using the resting electroencephalogram (EEG) showed that posterior versus anterior theta activity (around 4-8 Hz) is consistently associated with agency, reflecting the dopaminergic core of extraversion (i.e., incentive motivation, positive emotion). Neuroimaging studies using various methodologies and experimental paradigms have converged on the anterior cingulate cortex (ACC) as a neurophysiological correlate of extraversion. The aim of the present study is integrate these lines of research by testing the hypothesis that posterior versus anterior EEG theta is at least partly based on ACC theta activity. Resting EEG data were analyzed in N = 78 healthy, male participants extremely high or low in agentic extraversion (aE). Using the low-resolution electromagnetic tomography algorithm, we localized the sources of aE-dependent intracerebral theta activity within rostral subdivisions of the ACC. The posterior versus anterior index and theta current density within the rostral ACC were significantly correlated (r = -.52), and both displayed high retest stability across 5 hr and were associated with traits from the aE spectrum. These neurophysiological correlates of aE and their possible functional significance are discussed.

  5. EFFECT OF NITROGEN AND METAL ADDITIONS ON NITROGEN FIXATION ACTIVITY IN BIOLOGICAL SOIL CRUSTS

    NASA Astrophysics Data System (ADS)

    Alexander, K.; Lui, D.; Anbar, A. D.; Garcia-Pichel, F.; Hartnett, H. E.

    2009-12-01

    Biological soil crusts (BSCs) are diverse consortia of microorganisms that live in intimate association with soils in arid environments. Also called cryptogamic or microbiotic crusts, these communities can include cyanobacteria, algae, heterotrophic bacteria, fungi, lichens, and mosses. Together, these organisms provide many services to their surrounding ecosystems, including reduction of water runoff, promotion of water infiltration, and prevention of soil erosion. The cyanobacteria and algae also provide fixed carbon (C) to the soil through photosynthesis, and because atmospheric deposition of nitrogen (N) in arid environments is low, the major input of biologically available N comes from cyanobacteria capable of converting nitrogen gas (N2) to ammonium (NH4+). Biological soil crusts are easily destroyed by livestock grazing, motor vehicle travel, and many forms of recreational and agricultural land use. Loss of BSC cover can leave the soil vulnerable to intense erosion that can remove the nutrients necessary to sustain plant and animal life, thus accelerating the process of desertification. In order to preserve existing crusts and encourage the development of new crusts, it is crucial to understand the nutrient requirements of metabolism and growth in these microbial communities. This study investigated the affect of nitrogen and metal additions on N2-fixation activity in cyanobacterially-dominated crusts from the Colorado Plateau near Moab, Utah. Although N2-fixation has been studied in this system before, the affect of nutrient additions on N2-fixation activity has not been documented. The goal of this work was to understand how N and metal supplementation affects crust N metabolism. Three experiments were conducted to observe how N2-fixation activity changed with the addition of N, molybdenum (Mo), and vanadium (V). Molybdenum and vanadium were chosen because they are most commonly found at the active site of the enzyme nitrogenase, the molecule responsible

  6. Toward Efficient Thick Active PTB7 Photovoltaic Layers Using Diphenyl Ether as a Solvent Additive.

    PubMed

    Zheng, Yifan; Goh, Tenghooi; Fan, Pu; Shi, Wei; Yu, Junsheng; Taylor, André D

    2016-06-22

    The development of thick organic photovoltaics (OPV) could increase absorption in the active layer and ease manufacturing constraints in large-scale solar panel production. However, the efficiencies of most low-bandgap OPVs decrease substantially when the active layers exceed ∼100 nm in thickness (because of low crystallinity and a short exciton diffusion length). Herein, we report the use of solvent additive diphenyl ether (DPE) that facilitates the fabrication of thick (180 nm) active layers and triples the power conversion efficiency (PCE) of conventional thienothiophene-co-benzodithiophene polymer (PTB7)-based OPVs from 1.75 to 6.19%. These results demonstrate a PCE 20% higher than those of conventional (PTB7)-based OPV devices using 1,8-diiodooctane. Morphology studies reveal that DPE promotes the formation of nanofibrillar networks and ordered packing of PTB7 in the active layer that facilitate charge transport over longer distances. We further demonstrate that DPE improves the fill factor and photocurrent collection by enhancing the overall optical absorption, reducing the series resistance, and suppressing bimolecular recombination.

  7. Extracurricular Activity Participation in High School: Mechanisms Linking Participation to Math Achievement and 4-Year College Attendance

    ERIC Educational Resources Information Center

    Morris, David S.

    2016-01-01

    Extracurricular activity participation (EAP) has been positively linked with increased academic achievement and college attendance. However, the mechanisms linking EAP to educational outcomes are poorly understood. Using the Education Longitudinal Study of 2002 (ELS), this study contributes to our understanding of the relationship between EAP and…

  8. Structural features of piperazinyl-linked ciprofloxacin dimers required for activity against drug-resistant strains of Staphylococcus aureus.

    PubMed

    Kerns, Robert J; Rybak, Michael J; Kaatz, Glenn W; Vaka, Flamur; Cha, Raymond; Grucz, Richard G; Diwadkar, Veena U

    2003-07-07

    We previously demonstrated that piperazinyl-linked fluoroquinolone dimers possess potent antibacterial activity against drug-resistant strains of Staphylococcus aureus. In this study, we report the preparation and evaluation of a series of incomplete dimers toward ascertaining structural features of piperazinyl-linked ciprofloxacin dimers that render these agents refractory to fluoroquinolone-resistance mechanisms in Staphylococcus aureus.

  9. Bcl10 links saturated fat overnutrition with hepatocellular NF-kB activation and insulin resistance.

    PubMed

    Van Beek, Matthew; Oravecz-Wilson, Katherine I; Delekta, Phillip C; Gu, Shufang; Li, Xiangquan; Jin, Xiaohong; Apel, Ingrid J; Konkle, Katy S; Feng, Yongjia; Teitelbaum, Daniel H; Ruland, Jürgen; McAllister-Lucas, Linda M; Lucas, Peter C

    2012-05-31

    Excess serum free fatty acids (FFAs) are fundamental to the pathogenesis of insulin resistance. With high-fat feeding, FFAs activate NF-kB in target tissues, initiating negative crosstalk with insulin signaling. However, the mechanisms underlying FFA-dependent NF-kB activation remain unclear. Here, we demonstrate that the saturated FA, palmitate, requires Bcl10 for NF-kB activation in hepatocytes. Uptake of palmitate, metabolism to diacylglycerol, and subsequent activation of protein kinase C (PKC) appear to mechanistically link palmitate with Bcl10, known as a central component of a signaling complex that, along with CARMA3 and MALT1, activates NF-kB downstream of selected cell surface receptors. Consequently, Bcl10-deficient mice are protected from hepatic NF-kB activation and insulin resistance following brief high-fat diet, suggesting that Bcl10 plays a major role in the metabolic consequences of acute overnutrition. Surprisingly, while CARMA3 also participates in the palmitate response, MALT1 is completely dispensable, thereby revealing an apparent nonclassical role for Bcl10 in NF-kB signaling.

  10. Targeted Gene Addition to a Safe Harbor locus in human CD34+ Hematopoietic Stem Cells for Correction of X-linked Chronic Granulomatous Disease

    PubMed Central

    De Ravin, Suk See; Reik, Andreas; Liu, Pei-Qi; Li, Linhong; Wu, Xiaolin; Su, Ling; Raley, Castle; Theobald, Narda; Choi, Uimook; Song, Alexander H.; Chan, Andy; Pearl, Jocelynn R.; Paschon, David E.; Lee, Janet; Newcombe, Hannah; Koontz, Sherry; Sweeney, Colin; Shivak, David A.; Zarember, Kol A.; Peshwa, Madhusudan V.; Gregory, Philip D.; Urnov, Fyodor D.; Malech, Harry L.

    2016-01-01

    Gene therapy with genetically modified human CD34+ hematopoietic stem cells (HSCs) may be safer using targeted integration (TI) of transgenes into a genomic ‘safe harbor’ site than random viral integration. We demonstrate that temporally optimized delivery of zinc finger nuclease mRNA via electroporation and adeno associated virus (AAV) 6 delivery of donor constructs in human HSCs approaches clinically relevant levels of TI into the AAVS1 safe harbor locus. Up to 58% Venus-positive HSCs with 6–16% human cell marking were observed following engraftment into mice. In HSCs from patients with X-linked chronic granulomatous disease (X-CGD), caused by mutations in the gp91phox subunit of the NADPH oxidase, TI of a gp91phox transgene into AAVS1 in resulted in ~15% gp91phox expression and increased NADPH oxidase activity in ex vivo–derived neutrophils. In mice transplanted with corrected HSCs, 4–11% of human cells in the bone marrow expressed gp91phox. This method for TI into AAVS1 may be broadly applicable to correction of other monogenic diseases. PMID:26950749

  11. Performance enhancement with powdered activated carbon (PAC) addition in a membrane bioreactor (MBR) treating distillery effluent.

    PubMed

    Satyawali, Yamini; Balakrishnan, Malini

    2009-10-15

    This work investigated the effect of powdered activated carbon (PAC) addition on the operation of a membrane bioreactor (MBR) treating sugarcane molasses based distillery wastewater (spentwash). The 8L reactor was equipped with a submerged 30 microm nylon mesh filter with 0.05 m(2) filtration area. Detailed characterization of the commercial wood charcoal based PAC was performed before using it in the MBR. The MBR was operated over 200 days at organic loading rates (OLRs) varying from 4.2 to 6.9 kg m(-3)d(-1). PAC addition controlled the reactor foaming during start up and enhanced the critical flux by around 23%; it also prolonged the duration between filter cleaning. Operation at higher loading rates was possible and for a given OLR, the chemical oxygen demand (COD) removal was higher with PAC addition. However, biodegradation in the reactor was limited and the high molecular weight compounds were not affected by PAC supplementation. The functional groups on PAC appear to interact with the polysaccharide portion of the sludge, which may reduce its propensity to interact with the nylon mesh.

  12. Energy Landscape Topography Reveals the Underlying Link Between Binding Specificity and Activity of Enzymes.

    PubMed

    Chu, Wen-Ting; Wang, Jin

    2016-06-14

    Enzyme activity (often quantified by kcat/Km) is the main function of enzyme when it is active against the specific substrate. Higher or lower activities are highly desired for the design of novel enzyme and drug resistance. However, it is difficult to measure the activities of all possible variants and find the "hot-spot" within the limit of experimental time. In this study, we explore the underlying energy landscape of enzyme-substrate interactions and introduce the intrinsic specificity ratio (ISR), which reflects the landscape topography. By studying two concrete systems, we uncover the statistical correlation between the intrinsic specificity and the enzyme activity kcat/Km. This physics-based concept and method show that the energy landscape topography is valuable for understanding the relationship between enzyme specificity and activity. In addition, it can reveal the underlying mechanism of enzyme-substrate actions and has potential applications on enzyme design.

  13. Energy Landscape Topography Reveals the Underlying Link Between Binding Specificity and Activity of Enzymes

    NASA Astrophysics Data System (ADS)

    Chu, Wen-Ting; Wang, Jin

    2016-06-01

    Enzyme activity (often quantified by kcat/Km) is the main function of enzyme when it is active against the specific substrate. Higher or lower activities are highly desired for the design of novel enzyme and drug resistance. However, it is difficult to measure the activities of all possible variants and find the “hot-spot” within the limit of experimental time. In this study, we explore the underlying energy landscape of enzyme-substrate interactions and introduce the intrinsic specificity ratio (ISR), which reflects the landscape topography. By studying two concrete systems, we uncover the statistical correlation between the intrinsic specificity and the enzyme activity kcat/Km. This physics-based concept and method show that the energy landscape topography is valuable for understanding the relationship between enzyme specificity and activity. In addition, it can reveal the underlying mechanism of enzyme-substrate actions and has potential applications on enzyme design.

  14. Energy Landscape Topography Reveals the Underlying Link Between Binding Specificity and Activity of Enzymes

    PubMed Central

    Chu, Wen-Ting; Wang, Jin

    2016-01-01

    Enzyme activity (often quantified by kcat/Km) is the main function of enzyme when it is active against the specific substrate. Higher or lower activities are highly desired for the design of novel enzyme and drug resistance. However, it is difficult to measure the activities of all possible variants and find the “hot-spot” within the limit of experimental time. In this study, we explore the underlying energy landscape of enzyme-substrate interactions and introduce the intrinsic specificity ratio (ISR), which reflects the landscape topography. By studying two concrete systems, we uncover the statistical correlation between the intrinsic specificity and the enzyme activity kcat/Km. This physics-based concept and method show that the energy landscape topography is valuable for understanding the relationship between enzyme specificity and activity. In addition, it can reveal the underlying mechanism of enzyme-substrate actions and has potential applications on enzyme design. PMID:27298067

  15. Effects of Nutrient Addition on Belowground Stoichiometry and Microbial Activity in an Ombrotrophic Bog

    NASA Astrophysics Data System (ADS)

    Pinsonneault, A. J.; Moore, T. R.; Roulet, N. T.

    2015-12-01

    Ombrotrophic bogs are both nutrient-poor systems and important carbon (C) sinks yet there remains a dearth of information on the stoichiometry of C, nitrogen (N), phosphorus (P), and potassium (K), an important determinant of substrate quality for microorganisms, in these systems. In this study, we quantified the C, N, P, and K concentrations and stoichiometric ratios of both soil organic matter (SOM) and dissolved organic matter (DOM) as well as microbial extracellular enzyme activity from 0 - 10cm depth in a long-term fertilization experiment at Mer Bleue bog, Ontario, Canada. Though trends in C:N, C:P, and C:K between SOM and DOM seem to follow one another, preliminary results indicate that the stoichiometric ratios of DOM were at least an order of magnitude smaller than those of DOM suggesting that nutrient fertilization impacts the quality of DOM as a microbial substrate to a greater degree than SOM. C:N decreased with greater nitrogen addition but C:P and C:K increased; the magnitude of that increase being smaller in NPK treatments relative to N-only treatments suggesting co-limitation by P and/or K. This is further supported by the increase in activity of both the C-cycling enzyme, β-D-glucosidase (bdG), and the P-cycling enzyme, phosphatase (Phos), with greater nitrogen addition; particularly in NPK-treatments for bdG and N-only treatments for Phos. The activity of the N-cycling enzyme, N-acetyl-β-D-glucosaminidase, and the C-cycling enzyme, phenol oxidase, with greater N-addition suggests a decreased need to breakdown organic nitrogen to meet microbial N-requirements in the former and N-inhibition in the latter consistent with findings in the literature. Taken together, these results suggest that higher levels of nutrients impact both microbial substrate quality as well as the activity of microbial enzymes that are key in the decomposition process which may ultimately decrease the ability of peatlands to sequester carbon.

  16. Aromatic nitrogen mustard-based prodrugs: activity, selectivity, and the mechanism of DNA cross-linking.

    PubMed

    Chen, Wenbing; Han, Yanyan; Peng, Xiaohua

    2014-06-10

    Three novel H2O2-activated aromatic nitrogen mustard prodrugs (6-8) are reported. These compounds contain a DNA alkylating agent connected to a H2O2-responsive trigger by different electron-withdrawing linkers so that they are inactive towards DNA but can be triggered by H2O2 to release active species. The activity and selectivity of these compounds towards DNA were investigated by measuring DNA interstrand cross-link (ICL) formation in the presence or absence of H2O2. An electron-withdrawing linker unit, such as a quaternary ammonia salt (6), a carboxyamide (7), and a carbonate group (8), is sufficient to deactivate the aromatic nitrogen mustard resulting in less than 1.5 % cross-linking formation. However, H2O2 can restore the activity of the effectors by converting a withdrawing group to a donating group, therefore increasing the cross-linking efficiency (>20 %). The stability and reaction sites of the ICL products were determined, which revealed that alkylation induced by 7 and 8 not only occurred at the purine sites but also at the pyrimidine site. For the first time, we isolated and characterized the monomer adducts formed between the canonical nucleosides and the aromatic nitrogen mustard (15) which supported that nitrogen mustards reacted with dG, dA, and dC. The activation mechanism was studied by NMR spectroscopic analysis. An in vitro cytotoxicity assay demonstrated that compound 7 with a carboxyamide linker dramatically inhibited the growth of various cancer cells with a GI50 of less than 1 μM, whereas compound 6 with a charged linker did not show any obvious toxicity in all cell lines tested. These data indicated that a neutral carboxyamide linker is preferable for developing nitrogen mustard prodrugs. Our results showed that 7 is a potent anticancer prodrug that can serve as a model compound for further development. We believe these novel aromatic nitrogen mustards will inspire further and effective applications.

  17. Microbial Community Dynamics and Activity Link to Indigo Production from Indole in Bioaugmented Activated Sludge Systems

    PubMed Central

    Deng, Jie; Deng, Ye; Van Nostrand, Joy D.; Wu, Liyou; He, Zhili; Qin, Yujia; Zhou, Jiti; Zhou, Jizhong

    2015-01-01

    Biosynthesis of the popular dyestuff indigo from indole has been comprehensively studied using pure cultures, but less has been done to characterize the indigo production by microbial communities. In our previous studies, a wild strain Comamonas sp. MQ was isolated from activated sludge and the recombinant Escherichia coli nagAc carrying the naphthalene dioxygenase gene (nag) from strain MQ was constructed, both of which were capable of producing indigo from indole. Herein, three activated sludge systems, G1 (non-augmented control), G2 (augmented with Comamonas sp. MQ), and G3 (augmented with recombinant E. coli nagAc), were constructed to investigate indigo production. After 132-day operation, G3 produced the highest yields of indigo (99.5 ± 3.0 mg/l), followed by G2 (27.3 ± 1.3 mg/l) and G1 (19.2 ± 1.2 mg/l). The microbial community dynamics and activities associated with indigo production were analyzed by Illumina Miseq sequencing of 16S rRNA gene amplicons. The inoculated strain MQ survived for at least 30 days, whereas E. coli nagAc was undetectable shortly after inoculation. Quantitative real-time PCR analysis suggested the abundance of naphthalene dioxygenase gene (nagAc) from both inoculated strains was strongly correlated with indigo yields in early stages (0–30 days) (P < 0.001) but not in later stages (30–132 days) (P > 0.10) of operation. Based on detrended correspondence analysis (DCA) and dissimilarity test results, the communities underwent a noticeable shift during the operation. Among the four major genera (> 1% on average), the commonly reported indigo-producing populations Comamonas and Pseudomonas showed no positive relationship with indigo yields (P > 0.05) based on Pearson correlation test, while Alcaligenes and Aquamicrobium, rarely reported for indigo production, were positively correlated with indigo yields (P < 0.05). This study should provide new insights into our understanding of indigo bio-production by microbial communities

  18. Activity-dependent regulation of genes implicated in X-linked non-specific mental retardation.

    PubMed

    Boda, B; Mas, C; Muller, D

    2002-01-01

    X-linked forms of non-specific mental retardation are complex disorders, for which mutations in several genes have recently been identified. These include OPHN1, GDI1, PAK3, IL1RAPL, TM4SF2, FMR2 and RSK2. To investigate the mechanisms through which alterations of these gene products could result in cognitive impairment, we analyzed their expression using quantitative PCR technique in two in vitro models of activity-dependent gene regulation: kainate-induced seizures and long-term synaptic potentiation (LTP). We found that the level of expression of four genes, PAK3, IL1RAPL, RSK2 and TM4SF2, was significantly up-regulated following kainate treatment. Furthermore we observed a significant increase in mRNA levels of PAK3 and IL1RAPL following LTP induction. These results suggest a possible role for these four genes in activity-dependent brain plasticity.

  19. GABA and neuroligin signaling: linking synaptic activity and adhesion in inhibitory synapse development

    PubMed Central

    Huang, Z. Josh; Scheiffele, Peter

    2013-01-01

    GABA-mediated synaptic inhibition is crucial in neural circuit operations. In mammalian brains, the development of inhibitory synapses and innervation patterns is often a prolonged postnatal process, regulated by neural activity. Emerging evidence indicates that GABA acts beyond inhibitory transmission and regulates inhibitory synapse development. Indeed, GABAA receptors not only function as chloride channels that regulate membrane voltage and conductance but also play structural roles in synapse maturation and stabilization. The link from GABAA receptors to post- and pre- synaptic adhesion is likely mediated, in part, by neuroligin-reurexin interactions, which are potent in promoting GABAergic synapse formation. Therefore, similar to glutamate signaling at excitatory synapse, GABA signaling may coordinate maturation of pre- and post- synaptic sites at inhibitory synapses. Defining the many steps from GABA signaling to receptor trafficking/stability and neuroligin function will provide further mechanistic insights into activity-dependent development and possibly plasticity of inhibitory synapses. PMID:18513949

  20. Spatiotemporal Analysis of a Glycolytic Activity Gradient Linked to Mouse Embryo Mesoderm Development.

    PubMed

    Bulusu, Vinay; Prior, Nicole; Snaebjornsson, Marteinn T; Kuehne, Andreas; Sonnen, Katharina F; Kress, Jana; Stein, Frank; Schultz, Carsten; Sauer, Uwe; Aulehla, Alexander

    2017-02-27

    How metabolism is rewired during embryonic development is still largely unknown, as it remains a major technical challenge to resolve metabolic activities or metabolite levels with spatiotemporal resolution. Here, we investigated metabolic changes during development of organogenesis-stage mouse embryos, focusing on the presomitic mesoderm (PSM). We measured glycolytic labeling kinetics from (13)C-glucose tracing experiments and detected elevated glycolysis in the posterior, more undifferentiated PSM. We found evidence that the spatial metabolic differences are functionally relevant during PSM development. To enable real-time quantification of a glycolytic metabolite with spatiotemporal resolution, we generated a pyruvate FRET-sensor reporter mouse line. We revealed dynamic changes in cytosolic pyruvate levels as cells transit toward a more anterior PSM state. Combined, our approach identifies a gradient of glycolytic activity across the PSM, and we provide evidence that these spatiotemporal metabolic changes are intrinsically linked to PSM development and differentiation.

  1. Chemical composition and cytotoxic and antimicrobial activity of Calycotome villosa (Poiret) link leaves.

    PubMed

    Loy, G; Cottiglia, F; Garau, D; Deidda, D; Pompei, R; Bonsignore, L

    2001-01-01

    The chemical composition of the essential oil and methanol extract of Calycotome villosa (Poiret) Link leaves collected in Sardinia (Italy) has been studied by analytical and spectroscopic methods. Falcarinol and some alcohols, terpenes, furan derivatives, and paraffins have been isolated from the essential oil. Thirteen alkaloids and falcarinol have been identified in the chloroform fraction of the basic methanol extract. Six flavonoids and four anthraquinones have been isolated in the chloroform fraction after acidification of the basic methanol extract. The cytotoxic and antimicrobial activities have also been evaluated. The essential oil, the methanol extract in toto, and the fraction of the basic extract showed strong cytotoxicity, whereas the fraction of the acid extract showed lower cytotoxicity. Furthermore, this fraction showed good antibacterial activity against Staphylococcus aureus, Bacillus lentus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Providencia rettgeri, and Morganella morganii. It can therefore be stated that this plant's cytotoxicity is prevalently due to falcarinol.

  2. Real-time fMRI links subjective experience with brain activity during focused attention

    PubMed Central

    Garrison, Kathleen A.; Scheinost, Dustin; Worhunsky, Patrick D.; Elwafi, Hani M.; Thornhill, Thomas A.; Thompson, Evan; Saron, Clifford; Desbordes, Gaëlle; Kober, Hedy; Hampson, Michelle; Gray, Jeremy R.; Constable, R. Todd; Papademetris, Xenophon; Brewer, Judson A.

    2013-01-01

    Recent advances in brain imaging have improved the measure of neural processes related to perceptual, cognitive and affective functions, yet the relation between brain activity and subjective experience remains poorly characterized. In part, it is a challenge to obtain reliable accounts of participant’s experience in such studies. Here we addressed this limitation by utilizing experienced meditators who are expert in introspection. We tested a novel method to link objective and subjective data, using real-time fMRI (rt-fMRI) to provide participants with feedback of their own brain activity during an ongoing task. We provided real-time feedback during a focused attention task from the posterior cingulate cortex, a hub of the default mode network shown to be activated during mind-wandering and deactivated during meditation. In a first experiment, both meditators and non-meditators reported significant correspondence between the feedback graph and their subjective experience of focused attention and mind-wandering. When instructed to volitionally decrease the feedback graph, meditators, but not non-meditators, showed significant deactivation of the posterior cingulate cortex. We were able to replicate these results in a separate group of meditators using a novel step-wise rt-fMRI discovery protocol in which participants were not provided with prior knowledge of the expected relationship between their experience and the feedback graph (i.e., focused attention versus mind-wandering). These findings support the feasibility of using rt-fMRI to link objective measures of brain activity with reports of ongoing subjective experience in cognitive neuroscience research, and demonstrate the generalization of expertise in introspective awareness to novel contexts. PMID:23684866

  3. Mycobacterium tuberculosis Activates Human Macrophage Peroxisome Proliferator-Activated Receptor γ Linking Mannose Receptor Recognition to Regulation of Immune Responses

    PubMed Central

    Rajaram, Murugesan V. S.; Brooks, Michelle N.; Morris, Jessica D.; Torrelles, Jordi B.; Azad, Abul K.; Schlesinger, Larry S.

    2010-01-01

    Mycobacterium tuberculosis enhances its survival in macrophages by suppressing immune responses in part through its complex cell wall structures. Peroxisome proliferator-activated receptor γ (PPARγ), a nuclear receptor superfamily member, is a transcriptional factor that regulates inflammation and has high expression in alternatively activated alveolar macrophages and macrophage-derived foam cells, both cell types relevant to tuberculosis pathogenesis. In this study, we show that virulent M. tuberculosis and its cell wall mannose-capped lipoarabinomannan induce PPARγ expression through a macrophage mannose receptor-dependent pathway. When activated, PPARγ promotes IL-8 and cyclooxygenase 2 expression, a process modulated by a PPARγ agonist or antagonist. Upstream, MAPK-p38 mediates cytosolic phospholipase A2 activation, which is required for PPARγ ligand production. The induced IL-8 response mediated by mannose-capped lipoarabinomannan and the mannose receptor is independent of TLR2 and NF-κB activation. In contrast, the attenuated Mycobacterium bovis bacillus Calmette-Guérin induces less PPARγ and preferentially uses the NF-κB–mediated pathway to induce IL-8 production. Finally, PPARγ knockdown in human macrophages enhances TNF production and controls the intracellular growth of M. tuberculosis. These data identify a new molecular pathway that links engagement of the mannose receptor, an important pattern recognition receptor for M. tuberculosis, with PPARγ activation, which regulates the macrophage inflammatory response, thereby playing a role in tuberculosis pathogenesis. PMID:20554962

  4. Direct evidence of complement activation in HELLP syndrome: A link to atypical hemolytic uremic syndrome.

    PubMed

    Vaught, Arthur J; Gavriilaki, Eleni; Hueppchen, Nancy; Blakemore, Karin; Yuan, Xuan; Seifert, Sara M; York, Sarah; Brodsky, Robert A

    2016-05-01

    HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe variant of pre-eclampsia whose pathogenesis remains unclear. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative complement pathway effectively treated with a complement inhibitor, eculizumab. Therefore, we used a functional complement assay, the modified Ham test, to analyze sera of women with classic or atypical HELLP syndrome, pre-eclampsia with severe features, normal pregnancies, and healthy nonpregnant women. Sera were also evaluated using levels of the terminal product of complement activation (C5b-9). We tested the in vitro ability of eculizumab to inhibit complement activation in HELLP serum. Increased complement activation was observed in participants with classic or atypical HELLP compared with those with normal pregnancies and nonpregnant controls. Mixing HELLP serum with eculizumab-containing serum resulted in a significant decrease in cell killing compared with HELLP serum alone. We found that HELLP syndrome is associated with increased complement activation as assessed with the modified Ham test. This assay may aid in the diagnosis of HELLP syndrome and could confirm that its pathophysiology is related to that of atypical hemolytic uremic syndrome.

  5. Radical scavenging-linked antioxidant activities of commonly used herbs and spices in Korea.

    PubMed

    Kim, Il-Suk; Yang, Mira; Goo, Tae-Hwa; Jo, Cheorun; Ahn, Dong-Uk; Park, Jung-Hyun; Lee, Ok-Hwan; Kang, Suk-Nam

    2012-08-01

    Herbs and spices not only variety and racy flavour to Korean foods, they also are the richest source for antioxidant power. The present study evaluates the radical scavenging-linked antioxidant activities of hot water extracts from commonly used herbs and spices in Korea. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical and superoxide anion scavenging activities of bay extract were 39.5% and 22.1%, respectively. The hydroxyl radical scavenging activity was in order of dill (50.0%) > bay (31.3%) > garlic (27.9%) > white pepper and black pepper (15.1-15.3%) > onion (10.1%) extracts. Bay extract had the highest total phenolic content (17.86 μg CE/g). High correlation coefficients were found between the total phenol content and DPPH radical scavenging activity (R = 0.9162). These results indicate that herbs and spices had high antioxidant activity that is partly due to the phenolic compounds and provide basic data for further development of processed food products.

  6. Controlling the corrosion and cathodic activation of magnesium via microalloying additions of Ge

    PubMed Central

    Liu, R. L.; Hurley, M. F.; Kvryan, A.; Williams, G.; Scully, J. R.; Birbilis, N.

    2016-01-01

    The evolution of corrosion morphology and kinetics for magnesium (Mg) have been demonstrated to be influenced by cathodic activation, which implies that the rate of the cathodic partial reaction is enhanced as a result of anodic dissolution. This phenomenon was recently demonstrated to be moderated by the use of arsenic (As) alloying as a poison for the cathodic reaction, leading to significantly improved corrosion resistance. The pursuit of alternatives to toxic As is important as a means to imparting a technologically safe and effective corrosion control method for Mg (and its alloys). In this work, Mg was microalloyed with germanium (Ge), with the aim of improving corrosion resistance by retarding cathodic activation. Based on a combined analysis herein, we report that Ge is potent in supressing the cathodic hydrogen evolution reaction (reduction of water) upon Mg, improving corrosion resistance. With the addition of Ge, cathodic activation of Mg subject to cyclic polarisation was also hindered, with beneficial implications for future Mg electrodes. PMID:27350286

  7. Chemistry, physico-chemistry and applications linked to biological activities of β-glucans.

    PubMed

    Barsanti, Laura; Passarelli, Vincenzo; Evangelista, Valtere; Frassanito, Anna Maria; Gualtieri, Paolo

    2011-03-01

    β-Glucans is the common name given to a group of chemically heterogeneous polysaccharides. They are long- or short-chain polymers of (1-->3)-β-linked glucose moieties which may be branched, with the branching chains linked to the backbone by a (1-->6)-β linkage. β-(1-->3)-Glucans are widely distributed in bacteria, algae, fungi and plants, where they are involved in cell wall structure and other biological function. β-Glucans have been shown to provide a remarkable range of health benefits, and are especially important against the two most common conventional causes of death in industrialized countries, i.e. cardiovascular diseases (where they promote healthy cholesterol and blood glucose levels) and cancer (where they enhance immune system functions). This Highlight provides a comprehensive and up-to-date commentary on β-glucans, their chemistry, physico-chemistry, functional role in immunological responses, and possible applications as therapeutic tools. In addition, we discuss the mechanism behind their health benefits, which are not yet fully understood.

  8. Hydrogen Peroxide Linked to Lysine Oxidase Activity Facilitates Biofilm Differentiation and Dispersal in Several Gram-Negative Bacteria▿

    PubMed Central

    Mai-Prochnow, Anne; Lucas-Elio, Patricia; Egan, Suhelen; Thomas, Torsten; Webb, Jeremy S.; Sanchez-Amat, Antonio; Kjelleberg, Staffan

    2008-01-01

    The marine bacterium Pseudoalteromonas tunicata produces an antibacterial and autolytic protein, AlpP, which causes death of a subpopulation of cells during biofilm formation and mediates differentiation, dispersal, and phenotypic variation among dispersal cells. The AlpP homologue (LodA) in the marine bacterium Marinomonas mediterranea was recently identified as a lysine oxidase which mediates cell death through the production of hydrogen peroxide. Here we show that AlpP in P. tunicata also acts as a lysine oxidase and that the hydrogen peroxide generated is responsible for cell death within microcolonies during biofilm development in both M. mediterranea and P. tunicata. LodA-mediated biofilm cell death is shown to be linked to the generation of phenotypic variation in growth and biofilm formation among M. mediterranea biofilm dispersal cells. Moreover, AlpP homologues also occur in several other gram-negative bacteria from diverse environments. Our results show that subpopulations of cells in microcolonies also die during biofilm formation in two of these organisms, Chromobacterium violaceum and Caulobacter crescentus. In all organisms, hydrogen peroxide was implicated in biofilm cell death, because it could be detected at the same time as the killing occurred, and the addition of catalase significantly reduced biofilm killing. In C. violaceum the AlpP-homologue was clearly linked to biofilm cell death events since an isogenic mutant (CVMUR1) does not undergo biofilm cell death. We propose that biofilm killing through hydrogen peroxide can be linked to AlpP homologue activity and plays an important role in dispersal and colonization across a range of gram-negative bacteria. PMID:18502869

  9. Synthesis of binder-like molecules covalently linked to silicon nanoparticles and application as anode material for lithium-ion batteries without the use of electrolyte additives

    NASA Astrophysics Data System (ADS)

    Assresahegn, Birhanu Desalegn; Bélanger, Daniel

    2017-03-01

    A chemically modified silicon anode is prepared for application as anode in lithium-ion batteries by covalent attachment of polyacrylic acid to enable self-adhesion between the active material particles. The polyacrylic acid polymer is formed by atom transfer radical polymerization using 1-(bromoethyl)benzene initiator groups initially bonded to a hydrogenated silicon surface. The grafting of 1-(bromoethyl)benzene and polyacrylic acid is confirmed by various material characterization techniques. The electrochemical performance of the silicon anodes is also evaluated by galvanostatic cycling. The chemically modified composite silicon anode (with active material loading of 0.9-1 mg cm-2) showed a significantly improved performance in terms of: gravimetric capacitance (more than 2000 mAh g-1) after 300 cycles and 80% capacity retention with an average 99.6% Coulombic efficiency at a current density of 0.34 A g-1. However, the unmodified electrode cycled 75 times in the same conditions only retains 46% of its initial capacity with an average 95.1% Coulombic efficiency. The new composite Si electrode performs better at high charge/discharge rate and allows the use of larger proportion of the active material by reducing the amount of binder. It is noteworthy that these composite silicon electrodes are tested without the use of expensive electrolyte additives.

  10. Target detection in active polarization images perturbed with additive noise and illumination nonuniformity.

    PubMed

    Bénière, Arnaud; Goudail, François; Dolfi, Daniel; Alouini, Mehdi

    2009-07-01

    Active imaging systems that illuminate a scene with polarized light and acquire two images in two orthogonal polarizations yield information about the intensity contrast and the orthogonal state contrast (OSC) in the scene. Both contrasts are relevant for target detection. However, in real systems, the illumination is often spatially or temporally nonuniform. This creates artificial intensity contrasts that can lead to false alarms. We derive generalized likelihood ratio test (GLRT) detectors, for which intensity information is taken into account or not and determine the relevant expressions of the contrast in these two situations. These results are used to determine in which cases considering intensity information in addition to polarimetric information is relevant or not.

  11. Effect of conductive additives to gel electrolytes on activated carbon-based supercapacitors

    NASA Astrophysics Data System (ADS)

    Barzegar, Farshad; Dangbegnon, Julien K.; Bello, Abdulhakeem; Momodu, Damilola Y.; Johnson, A. T. Charlie; Manyala, Ncholu

    2015-09-01

    This article is focused on polymer based gel electrolyte due to the fact that polymers are cheap and can be used to achieve extended potential window for improved energy density of the supercapacitor devices when compared to aqueous electrolytes. Electrochemical characterization of a symmetric supercapacitor devices based on activated carbon in different polyvinyl alcohol (PVA) based gel electrolytes was carried out. The device exhibited a maximum energy density of 24 Wh kg-1 when carbon black was added to the gel electrolyte as conductive additive. The good energy density was correlated with the improved conductivity of the electrolyte medium which is favorable for fast ion transport in this relatively viscous environment. Most importantly, the device remained stable with no capacitance lost after 10,000 cycles.

  12. Patterns of Longitudinal Neural Activity Linked to Different Cognitive Profiles in Parkinson's Disease

    PubMed Central

    Nagano-Saito, Atsuko; Al-Azzawi, Mohamed S.; Hanganu, Alexandru; Degroot, Clotilde; Mejia-Constain, Béatriz; Bedetti, Christophe; Lafontaine, Anne-Louise; Soland, Valérie; Chouinard, Sylvain; Monchi, Oury

    2016-01-01

    Mild cognitive impairment in Parkinson's disease (PD) has been linked with functional brain changes. Previously, using functional magnetic resonance imaging (fMRI), we reported reduced cortico-striatal activity in patients with PD who also had mild cognitive impairment (MCI) vs. those who did not (non-MCI). We followed up these patients to investigate the longitudinal effect on the neural activity. Twenty-four non-demented patients with Parkinson's disease (non-MCI: 12, MCI: 12) were included in the study. Each participant underwent two fMRIs while performing the Wisconsin Card Sorting Task 20 months apart. The non-MCI patients recruited the usual cognitive corticostriatal loop at the first and second sessions (Time 1 and Time 2, respectively). However, decreased activity was observed in the cerebellum and occipital area and increased activity was observed in the medial prefrontal cortex and parietal lobe during planning set-shift at Time 2. Increased activity in the precuneus was also demonstrated while executing set-shifts at Time 2. The MCI patients revealed more activity in the frontal, parietal and occipital lobes during planning set-shifts, and in the parietal and occipital lobes, precuneus, and cerebellum, during executing set-shift at Time 2. Analysis regrouping of both groups of PD patients revealed that hippocampal and thalamic activity at Time 1 was associated with less cognitive decline over time. Our results reveal that functional alteration along the time-points differed between the non-MCI and MCI patients. They also underline the importance of preserving thalamic and hippocampal function with respect to cognitive decline over time. PMID:27932974

  13. Linking trait-based phenotypes to prefrontal cortex activation during inhibitory control.

    PubMed

    Rodrigo, Achala H; Di Domenico, Stefano I; Graves, Bryanna; Lam, Jaeger; Ayaz, Hasan; Bagby, R Michael; Ruocco, Anthony C

    2016-01-01

    Inhibitory control is subserved in part by discrete regions of the prefrontal cortex whose functionality may be altered according to specific trait-based phenotypes. Using a unified model of normal range personality traits, we examined activation within lateral and medial aspects of the prefrontal cortex during a manual go/no-go task. Evoked hemodynamic oxygenation within the prefrontal cortex was measured in 106 adults using a 16-channel continuous-wave functional near-infrared spectroscopy system. Within lateral regions of the prefrontal cortex, greater activation was associated with higher trait levels of extraversion, agreeableness and conscientiousness, and lower neuroticism. Higher agreeableness was also related to more activation in the medial prefrontal cortex during inhibitory control. These results suggest that personality traits reflecting greater emotional stability, extraversion, agreeableness and conscientiousness may be associated with more efficient recruitment of control processes subserved by lateral regions of the prefrontal cortex. These findings highlight key links between trait-based phenotypes and neural activation patterns in the prefrontal cortex underlying inhibitory control.

  14. Linking trait-based phenotypes to prefrontal cortex activation during inhibitory control

    PubMed Central

    Rodrigo, Achala H.; Di Domenico, Stefano I.; Graves, Bryanna; Lam, Jaeger; Ayaz, Hasan; Bagby, R. Michael

    2016-01-01

    Inhibitory control is subserved in part by discrete regions of the prefrontal cortex whose functionality may be altered according to specific trait-based phenotypes. Using a unified model of normal range personality traits, we examined activation within lateral and medial aspects of the prefrontal cortex during a manual go/no-go task. Evoked hemodynamic oxygenation within the prefrontal cortex was measured in 106 adults using a 16-channel continuous-wave functional near-infrared spectroscopy system. Within lateral regions of the prefrontal cortex, greater activation was associated with higher trait levels of extraversion, agreeableness and conscientiousness, and lower neuroticism. Higher agreeableness was also related to more activation in the medial prefrontal cortex during inhibitory control. These results suggest that personality traits reflecting greater emotional stability, extraversion, agreeableness and conscientiousness may be associated with more efficient recruitment of control processes subserved by lateral regions of the prefrontal cortex. These findings highlight key links between trait-based phenotypes and neural activation patterns in the prefrontal cortex underlying inhibitory control. PMID:26163672

  15. Choline-releasing glycerophosphodiesterase EDI3 links the tumor metabolome to signaling network activities

    PubMed Central

    Marchan, Rosemarie; Lesjak, Michaela S.; Stewart, Joanna D.; Winter, Roland; Seeliger, Janine; Hengstler, Jan G.

    2012-01-01

    Recently, EDI3 was identified as a key factor for choline metabolism that controls tumor cell migration and is associated with metastasis in endometrial carcinomas. EDI3 cleaves glycerophosphocholine (GPC) to form choline and glycerol-3-phosphate (G3P). Choline is then further metabolized to phosphatidylcholine (PtdC), the major lipid in membranes and a key player in membrane-mediated cell signaling. The second product, G3P, is a precursor molecule for several lipids with central roles in signaling, for example lysophosphatidic acid (LPA), phosphatidic acid (PA) and diacylglycerol (DAG). LPA activates intracellular signaling pathways by binding to specific LPA receptors, including membrane-bound G protein-coupled receptors and the intracellular nuclear receptor, PPARγ. Conversely, PA and DAG mediate signaling by acting as lipid anchors that bind and activate several signaling proteins. For example, binding of GTPases and PKC to PA and DAG, respectively, increases the activation of signaling networks, mediating processes such as migration, adhesion, proliferation or anti-apoptosis—all relevant for tumor development. We present a concept by which EDI3 either directly generates signaling molecules or provides “membrane anchors” for downstream signaling factors. As a result, EDI3 links choline metabolism to signaling activities resulting in a more malignant phenotype. PMID:23114620

  16. Preparation, characterization, and antifungal activity of hymexazol-linked chitosan derivatives

    NASA Astrophysics Data System (ADS)

    Li, Yan; Qin, Yukun; Liu, Song; Li, Pengcheng; Xing, Rong'e.

    2016-09-01

    In this study, three hymexazol-linked chitosan derivatives (HML-CS) were synthesized and their structures confirmed by Fourier transform infrared and elemental analysis. Linkage ratios were measured by high performance liquid chromatography. The derivatives' antifungal activity against the plant pathogenic fungi Rhizoctonia solani CGMCC 3.28 and Gibberella zeae CGMCC 3.42 were investigated at concentrations of 100, 200, and 400 mg/L. These HML-CS derivatives exhibited stronger antifungal activity than CS alone. HML-CS-1 showed the best antifungal activity against G. zeae, whose antifungal index was 65.9% at 400 mg/L, and also showed the best antifungal activity against R. solani, whose antifungal index was 52.7% at 400 mg/L. This conjugation of CS and HML suggested the presence of synergistic effects between the moieties and indicated that these derivatives possessed great potential as novel fungicides and require further research for the development of applications in crop protection.

  17. Enhanced high-solids anaerobic digestion of waste activated sludge by the addition of scrap iron.

    PubMed

    Zhang, Yaobin; Feng, Yinghong; Yu, Qilin; Xu, Zibin; Quan, Xie

    2014-05-01

    Anaerobic digestion of waste activated sludge usually requires pretreatment procedure to improve the bioavailability of sludge, which involves considerable energy and high expenditures. This study proposes a cost-effective method for enhanced anaerobic digestion of sludge without a pretreatment by directly adding iron into the digester. The results showed that addition of Fe(0) powder could enhance 14.46% methane yield, and Fe scrap (clean scrap) could further enhance methane yield (improving rate 21.28%) because the scrap has better mass transfer efficiency with sludge and liquid than Fe(0) powder. The scrap of Fe with rust (rusty scrap) could induce microbial Fe(III) reduction, which resulted in achieving the highest methane yield (improving rate 29.51%), and the reduction rate of volatile suspended solids (VSS) was also highest (48.27%) among Fe powder, clean scrap and rusty scrap. PCR-DGGE proved that the addition of rusty scrap could enhance diversity of acetobacteria and enrich iron-reducing bacteria to enhance degradation of complex substrates.

  18. Multimodal sensory integration during sequential eating--linking chewing activity, aroma release, and aroma perception over time.

    PubMed

    Leclercq, Ségolène; Blancher, Guillaume

    2012-10-01

    The respective effects of chewing activity, aroma release from a gelled candy, and aroma perception were investigated. Specifically, the study aimed at 1) comparing an imposed chewing and swallowing pattern (IP) and free protocol (FP) on panelists for in vivo measurements, 2) investigating carryover effects in sequential eating, and 3) studying the link between instrumental data and their perception counterpart. Chewing activity, in-nose aroma concentration, and aroma perception over time were measured by electromyography, proton transfer reaction-mass spectrometry, and time intensity, respectively. Model gel candies were flavored at 2 intensity levels (low-L and high-H). The panelists evaluated 3 sequences (H then H, H then L, and L then H) in duplicates with both IP and FP. They scored aroma intensity over time while their in-nose aroma concentrations and their chewing activity were measured. Overall, only limited advantages were found in imposing a chewing and swallowing pattern for instrumental and sensory data. In addition, the study highlighted the role of brain integration on perceived intensity and dynamics of perception, in the framework of sequential eating without rinsing. Because of the presence of adaptation phenomena, contrast effect, and potential taste and texture cross-modal interaction with aroma perception, it was concluded that dynamic in-nose concentration data provide only one part of the perception picture and therefore cannot be used alone in prediction models.

  19. Why are early maturing girls less active? Links between pubertal development, psychological well-being, and physical activity among girls at ages 11 and 13

    PubMed Central

    Davison, Kirsten Krahnstoever; Werder, Jessica L; Trost, Stewart G; Baker, Birgitta L; Birch, Leann L

    2007-01-01

    Previous research has shown that early maturing girls at age 11 have lower subsequent physical activity at age 13 in comparison to later maturing girls. Possible reasons for this association have not been assessed. This study examines girls’ psychological response to puberty and their enjoyment of physical activity as intermediary factors linking pubertal maturation and physical activity. Participants included 178 girls who were assessed at age 11, of whom 168 were reassessed at age 13. All participants were non-Hispanic white and resided in the U.S. Three measures of pubertal development were obtained at age 11 including Tanner breast stage, estradiol levels, and mothers’ reports of girls’ development on the Pubertal Development Scale (PDS). Measures of psychological well-being at ages 11 and 13 included depression, global self worth, perceived athletic competence, maturation fears, and body esteem. At age 13, girls’ enjoyment of physical activity was assessed using the Physical Activity Enjoyment Scale and their daily minutes of moderate to vigorous physical activity (MVPA) was assessed using objective monitoring. Structural Equation Modeling was used to assess direct and indirect pathways between pubertal development at age 11 and MVPA at age 13. In addition to a direct effect of pubertal development on MVPA, indirect effects were found for depression, global self worth and maturity fears controlling for covariates. In each instance, more advanced pubertal development at age 11 was associated with lower psychological well-being at age 13, which predicted lower enjoyment of physical activity at age 13 and in turn lower MVPA. Results from this study suggest that programs designed to increase physical activity among adolescent girls should address the self-consciousness and discontent that girls’ experience with their bodies during puberty, particularly if they mature earlier than their peers, and identify activities or settings that make differences in

  20. Myosin III-mediated cross-linking and stimulation of actin bundling activity of Espin

    PubMed Central

    Liu, Haiyang; Li, Jianchao; Raval, Manmeet H; Yao, Ningning; Deng, Xiaoying; Lu, Qing; Nie, Si; Feng, Wei; Wan, Jun; Yengo, Christopher M; Liu, Wei; Zhang, Mingjie

    2016-01-01

    Class III myosins (Myo3) and actin-bundling protein Espin play critical roles in regulating the development and maintenance of stereocilia in vertebrate hair cells, and their defects cause hereditary hearing impairments. Myo3 interacts with Espin1 through its tail homology I motif (THDI), however it is not clear how Myo3 specifically acts through Espin1 to regulate the actin bundle assembly and stabilization. Here we discover that Myo3 THDI contains a pair of repeat sequences capable of independently and strongly binding to the ankyrin repeats of Espin1, revealing an unexpected Myo3-mediated cross-linking mechanism of Espin1. The structures of Myo3 in complex with Espin1 not only elucidate the mechanism of the binding, but also reveal a Myo3-induced release of Espin1 auto-inhibition mechanism. We also provide evidence that Myo3-mediated cross-linking can further promote actin fiber bundling activity of Espin1. DOI: http://dx.doi.org/10.7554/eLife.12856.001 PMID:26785147

  1. Peroxisome proliferator-activated receptor agonists modulate neuropathic pain: a link to chemokines?

    PubMed Central

    Freitag, Caroline M.; Miller, Richard J.

    2014-01-01

    Chronic pain presents a widespread and intractable medical problem. While numerous pharmaceuticals are used to treat chronic pain, drugs that are safe for extended use and highly effective at treating the most severe pain do not yet exist. Chronic pain resulting from nervous system injury (neuropathic pain) is common in conditions ranging from multiple sclerosis to HIV-1 infection to type II diabetes. Inflammation caused by neuropathy is believed to contribute to the generation and maintenance of neuropathic pain. Chemokines are key inflammatory mediators, several of which (MCP-1, RANTES, MIP-1α, fractalkine, SDF-1 among others) have been linked to chronic, neuropathic pain in both human conditions and animal models. The important roles chemokines play in inflammation and pain make them an attractive therapeutic target. Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors known for their roles in metabolism. Recent research has revealed that PPARs also play a role in inflammatory gene repression. PPAR agonists have wide-ranging effects including inhibition of chemokine expression and pain behavior reduction in animal models. Experimental evidence suggests a connection between the pain ameliorating effects of PPAR agonists and suppression of inflammatory gene expression, including chemokines. In early clinical research, one PPARα agonist, palmitoylethanolamide (PEA), shows promise in relieving chronic pain. If this link can be better established, PPAR agonists may represent a new drug therapy for neuropathic pain. PMID:25191225

  2. 77 FR 67655 - Agency Information Collection Activities; Proposed Collection; Comment Request; Food Additive...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-13

    ...) Moderate Category: For a food additive petition without complex chemistry, manufacturing, efficacy, or...) Complex Category: For a food additive petition with complex chemistry, manufacturing, efficacy, and/or... investigational food additive file without complex chemistry, manufacturing, efficacy, or safety issues,...

  3. Enhancing the adsorption of ionic liquids onto activated carbon by the addition of inorganic salts

    PubMed Central

    Neves, Catarina M. S. S.; Lemus, Jesús; Freire, Mara G.; Palomar, Jose; Coutinho, João A. P.

    2014-01-01

    Most ionic liquids (ILs) are either water soluble or present a non-negligible miscibility with water that may cause some harmful effects upon their release into the environment. Among other methods, adsorption of ILs onto activated carbon (AC) has shown to be an effective technique to remove these compounds from aqueous solutions. However, this method has proved to be viable only for hydrophobic ILs rather than for the hydrophilic that, being water soluble, have a larger tendency for contamination. In this context, an alternative approach using the salting-out ability of inorganic salts is here proposed to enhance the adsorption of hydrophilic ILs onto activated carbon. The effect of the concentrations of Na2SO4 on the adsorption of five ILs onto AC was investigated. A wide range of ILs that allow the inspection of the IL cation family (imidazolium- and pyridinium-based) and the anion nature (accounting for its hydrophilicity and fluorination) through the adsorption onto AC was studied. In general, it is shown that the use of Na2SO4 enhances the adsorption of ILs onto AC. In particular, this effect is highly relevant when dealing with hydrophilic ILs that are those that are actually poorly removed by AC. In addition, the COnductor like Screening MOdel for Real Solvents (COSMO-RS) was used aiming at complementing the experimental data obtained. This work contributes with the development of novel methods to remove ILs from water streams aiming at creating “greener” processes. PMID:25516713

  4. Novel composite plastics containing silver(I) acylpyrazolonato additives display potent antimicrobial activity by contact.

    PubMed

    Marchetti, Fabio; Palmucci, Jessica; Pettinari, Claudio; Pettinari, Riccardo; Condello, Francesca; Ferraro, Stefano; Marangoni, Mirko; Crispini, Alessandra; Scuri, Stefania; Grappasonni, Iolanda; Cocchioni, Mario; Nabissi, Massimo; Chierotti, Michele R; Gobetto, Roberto

    2015-01-07

    New silver(I) acylpyrazolonato derivatives displaying a mononuclear, polynuclear, or ionic nature, as a function of the ancillary azole ligands used in the synthesis, have been fully characterized by thermal analysis, solution NMR spectroscopy, solid-state IR and NMR spectroscopies, and X-ray diffraction techniques. These derivatives have been embedded in polyethylene (PE) matrix, and the antimicrobial activity of the composite materials has been tested against three bacterial strains (E. coli, P. aeruginosa, and S. aureus): Most of the composites show antimicrobial action comparable to PE embedded with AgNO3 . Tests by contact and release tests for specific migration of silver from PE composites clearly indicate that, at least in the case of the PE, for composites containing polynuclear silver(I) additives, the antimicrobial action is exerted by contact, without release of silver ions. Moreover, PE composites can be re-used several times, displaying the same antimicrobial activity. Membrane permeabilization studies and induced reactive oxygen species (ROS) generation tests confirm the disorganization of bacterial cell membranes. The cytotoxic effect, evaluated in CD34(+) cells by MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazoliumbromide) and CFU (colony forming units) assays, indicates that the PE composites do not induce cytotoxicity in human cells. Studies of ecotoxicity, based on the test of Daphnia magna, confirm tolerability of the PE composites by higher organisms and exclude the release of Ag(+) ions in sufficient amounts to affect water environment.

  5. Macrophages exposed continuously to lipopolysaccharide and other agonists that act via toll-like receptors exhibit a sustained and additive activation state

    PubMed Central

    Hume, David A; Underhill, David M; Sweet, Matthew J; Ozinsky, Adrian O; Liew, Foo Y; Aderem, Alan

    2001-01-01

    Background Macrophages sense microorganisms through activation of members of the Toll-like receptor family, which initiate signals linked to transcription of many inflammation associated genes. In this paper we examine whether the signal from Toll-like receptors [TLRs] is sustained for as long as the ligand is present, and whether responses to different TLR agonists are additive. Results RAW264 macrophage cells were doubly-transfected with reporter genes in which the IL-12p40, ELAM or IL-6 promoter controls firefly luciferase, and the human IL-1β promoter drives renilla luciferase. The resultant stable lines provide robust assays of macrophage activation by TLR stimuli including LPS [TLR4], lipopeptide [TLR2], and bacterial DNA [TLR9], with each promoter demonstrating its own intrinsic characteristics. With each of the promoters, luciferase activity was induced over an 8 hr period, and thereafter reached a new steady state. Elevated expression required the continued presence of agonist. Sustained responses to different classes of agonist were perfectly additive. This pattern was confirmed by measuring inducible cytokine production in the same cells. While homodimerization of TLR4 mediates responses to LPS, TLR2 appears to require heterodimerization with another receptor such as TLR6. Transient expression of constitutively active forms of TLR4 or TLR2 plus TLR6 stimulated IL-12 promoter activity. The effect of LPS, a TLR4 agonist, was additive with that of TLR2/6 but not TLR4, whilst that of lipopeptide, a TLR2 agonist, was additive with TLR4 but not TLR2/6. Actions of bacterial DNA were additive with either TLR4 or TLR2/6. Conclusions These findings indicate that maximal activation by any one TLR pathway does not preclude further activation by another, suggesting that common downstream regulatory components are not limiting. Upon exposure to a TLR agonist, macrophages enter a state of sustained activation in which they continuously sense the presence of a

  6. Development of an Accelerometer-Linked Online Intervention System to Promote Physical Activity in Adolescents

    PubMed Central

    Guthrie, Nicole; Bradlyn, Andrew; Thompson, Sharon K.; Yen, Sophia; Haritatos, Jana; Dillon, Fred; Cole, Steve W.

    2015-01-01

    Most adolescents do not achieve the recommended levels of moderate-to-vigorous physical activity (MVPA), placing them at increased risk for a diverse array of chronic diseases in adulthood. There is a great need for scalable and effective interventions that can increase MVPA in adolescents. Here we report the results of a measurement validation study and a preliminary proof-of-concept experiment testing the impact of Zamzee, an accelerometer-linked online intervention system that combines proximal performance feedback and incentive motivation features to promote MVPA. In a calibration study that parametrically varied levels of physical activity in 31 12-14 year-old children, the Zamzee activity meter was shown to provide a valid measure of MVPA (sensitivity in detecting MVPA = 85.9%, specificity = 97.5%, and r = .94 correspondence with the benchmark RT3 accelerometer system; all p < .0001). In a subsequent randomized controlled multi-site experiment involving 182 middle school-aged children assessed for MVPA over 6 wks, intent-to-treat analyses found that those who received access to the Zamzee intervention had average MVPA levels 54% greater than those of a passive control group (p < 0.0001) and 68% greater than those of an active control group that received access to a commercially available active videogame (p < .0001). Zamzee’s effects on MVPA did not diminish significantly over the course of the 6-wk study period, and were statistically significant in both females and males, and in normal- vs. high-BMI subgroups. These results provide promising initial indications that combining the Zamzee activity meter with online proximal performance feedback and incentive motivation features can positively impact MVPA levels in adolescents. PMID:26010359

  7. Secondary science teachers' use of laboratory activities: Linking epistemological beliefs, goals, and practices

    NASA Astrophysics Data System (ADS)

    Kang, Nam-Hwa; Wallace, Carolyn S.

    2005-01-01

    The purpose of this study was to explore how science teachers' epistemological beliefs and teaching goals are related to their use of lab activities. Research questions include (a) What are the teachers' epistemological beliefs pertaining to lab activities? (b) Why do the science teachers use lab activities? (c) How are the teachers' epistemological beliefs and instructional goals related to teaching actions? Two major aspects of epistemologies guided this study: ontological aspect (certainty/diversity of truth) and relational aspect (relationship between the knower and the known). The ontological aspect addresses whether one views knowledge as one certain truth or as tentative multiple truths. The relational aspect addresses whether one views him/herself as a receiver of prescribed knowledge separating self from knowledge construction or as an active meaning maker connecting self to the knowledge construction processes. More sophisticated epistemological beliefs include the acknowledgement of multiple interpretations of the same phenomena and active role of the knower in knowledge construction. Three experienced secondary science teachers were interviewed and observed throughout an academic course. The findings illustrate that a teacher's naïve epistemological beliefs are clearly reflected in the teacher's teaching practices. However, a teacher's sophisticated epistemological beliefs are not always clearly connected to the practice. This seems to be related to the necessary negotiation among their epistemological beliefs, teaching contexts, and instructional goals. Ontological and relational beliefs seem to be connected to different facets of teaching practices. Findings indicate that various syntheses of different aspects of epistemological beliefs and instructional goals are linked to teachers' diverse ways of using lab activities. Implications for research and teacher education are discussed.

  8. Secretion and N-linked glycosylation are required for prostatic acid phosphatase catalytic and antinociceptive activity.

    PubMed

    Hurt, Julie K; Fitzpatrick, Brendan J; Norris-Drouin, Jacqueline; Zylka, Mark J

    2012-01-01

    Secretory human prostatic acid phosphatase (hPAP) is glycosylated at three asparagine residues (N62, N188, N301) and has potent antinociceptive effects when administered to mice. Currently, it is unknown if these N-linked residues are required for hPAP protein stability and activity in vitro or in animal models of chronic pain. Here, we expressed wild-type hPAP and a series of Asn to Gln point mutations in the yeast Pichia pastoris X33 then analyzed protein levels and enzyme activity in cell lysates and in conditioned media. Pichia secreted wild-type recombinant (r)-hPAP into the media (6-7 mg protein/L). This protein was as active as native hPAP in biochemical assays and in mouse models of inflammatory pain and neuropathic pain. In contrast, the N62Q and N188Q single mutants and the N62Q, N188Q double mutant were expressed at lower levels and were less active than wild-type r-hPAP. The purified N62Q, N188Q double mutant protein was also 1.9 fold less active in vivo. The N301Q mutant was not expressed, suggesting a critical role for this residue in protein stability. To explicitly test the importance of secretion, a construct lacking the signal peptide of hPAP was expressed in Pichia and assayed. This "cellular" construct was not expressed at levels detectable by western blotting. Taken together, these data indicate that secretion and post-translational carbohydrate modifications are required for PAP protein stability and catalytic activity. Moreover, our findings indicate that recombinant hPAP can be produced in Pichia--a yeast strain that is used to generate biologics for therapeutic purposes.

  9. Additive effects of maternal iron deficiency and prenatal immune activation on adult behaviors in rat offspring.

    PubMed

    Harvey, Louise; Boksa, Patricia

    2014-08-01

    Both iron deficiency (ID) and infection are common during pregnancy and studies have described altered brain development in offspring as a result of these individual maternal exposures. Given their high global incidence, these two insults may occur simultaneously during pregnancy. We recently described a rat model which pairs dietary ID during pregnancy and prenatal immune activation. Pregnant rats were placed on iron sufficient (IS) or ID diets from embryonic day 2 (E2) until postnatal day 7, and administered the bacterial endotoxin, lipopolysaccharide (LPS) or saline on E15/16. In this model, LPS administration on E15 caused greater induction of the pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor-α, in ID dams compared to IS dams. This suggested that the combination of prenatal immune activation on a background of maternal ID might have more adverse neurodevelopmental consequences for the offspring than exposure to either insult alone. In this study we used this model to determine whether combined exposure to maternal ID and prenatal immune activation interact to affect juvenile and adult behaviors in the offspring. We assessed behaviors relevant to deficits in humans or animals that have been associated with exposure to either maternal ID or prenatal immune activation alone. Adult offspring from ID dams displayed significant deficits in pre-pulse inhibition of acoustic startle and in passive avoidance learning, together with increases in cytochrome oxidase immunohistochemistry, a marker of metabolic activity, in the ventral hippocampus immediately after passive avoidance testing. Offspring from LPS treated dams showed a significant increase in social behavior with unfamiliar rats, and subtle locomotor changes during exploration in an open field and in response to amphetamine. Surprisingly, there was no interaction between effects of the two insults on the behaviors assessed, and few observed alterations in juvenile behavior. Our findings

  10. Effects of heavy metal and other elemental additives to activated sludge on growth of Eisenia foetida

    SciTech Connect

    Hartenstein, R.; Neuhauser, E.F.; Narahara, A.

    1981-09-01

    The approximate level at which added concentrations of certain elements would cause an activated sludge to induce a toxic effect upon the growth of Eisenia foetida was determined. During 43 trials on sludge samples obtained throughout 1 year of study, earthworms grew from 3 to 10 mg live wt at hatching to 792 mg +- 18% (mean +- C.V.) in 8 weeks, when sludge was 24/sup 0/C and contained no additives. None of several elements commonly used in microbial growth media enhanced the growth rate of the earthworm. At salt concentrations up to about 6.6% on a dry wt basis, none of six anions tested was in and of itself toxic, while five of 15 cations - Co, Hg, Cu, Ni, and Cd - appeared specifically to inhibit growth rate or cause death. Manganese, Cr, and Pb were innocuous even at the highest levels of application - 22,000, 46,000, and 52,000 mg/kg, respectively. Neither the anionic nor cationic component of certain salts, such as NaCl or NH/sub 4/Cl, could be said to inhibit growth, which occurred only at high concentrations of these salts (about 3.3 and/or 6.6%). Below 7 mmho/cm, toxicity could not be correlated with electrolytic conductance, though higher values may help to explain the nonspecific growth inhibitory effects of salts like NaCl and KCl. Nor could toxicity ever be ascribed to hydrogen ion activity, since sludge pH was not altered even at the highest salt dose. It is concluded that except under very extreme conditions, the levels of heavy metals and salts generally found in activated sludges will not have an adverse affect on the growth of E. foetida.

  11. Alpha-hydroxybutyrate dehydrogenase activity in sex-linked muscular dystrophy.

    PubMed

    Johnston, H A; Wilkinson, J H; Withycombe, W A; Raymond, S

    1966-05-01

    In two families with severe sex-linked muscular dystrophy, high levels of alpha-hydroxybutyrate dehydrogenase (HBD), lactate dehydrogenase (LD), aspartate transaminase (AspT), aldolase, and creatine phosphokinase (CPK) were found in the sera of three young affected males. In both families the mother had a raised level of HBD activity. Four sisters of the three affected boys had raised serum enzyme levels, and they are regarded as presumptive carriers of the disease. Biopsy specimens of dystrophic muscle had LD and HBD contents which were significantly lower than those of control specimens, while the HBD/LD ratios were markedly greater. Muscle from two unaffected members of the same family also exhibited high ratios, indicating the presence of the electrophoretically fast LD isoenzymes, and this was confirmed by acrylamide-gel electrophoresis.

  12. K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8(+) T cell activation.

    PubMed

    Yang, Mingjin; Chen, Taoyong; Li, Xuelian; Yu, Zhou; Tang, Songqing; Wang, Chen; Gu, Yan; Liu, Yanfang; Xu, Sheng; Li, Weihua; Zhang, Xuemin; Wang, Jianli; Cao, Xuetao

    2015-12-01

    The key molecular mechanisms that control signaling via T cell antigen receptors (TCRs) remain to be fully elucidated. Here we found that Nrdp1, a ring finger-type E3 ligase, mediated Lys33 (K33)-linked polyubiquitination of the signaling kinase Zap70 and promoted the dephosphorylation of Zap70 by the acidic phosphatase-like proteins Sts1 and Sts2 and thereby terminated early TCR signaling in CD8(+) T cells. Nrdp1 deficiency significantly promoted the activation of naive CD8(+) T cells but not that of naive CD4(+) T cells after engagement of the TCR. Nrdp1 interacted with Zap70 and with Sts1 and Sts2 and connected K33 linkage of Zap70 to Sts1- and Sts2-mediated dephosphorylation. Our study suggests that Nrdp1 terminates early TCR signaling by inactivating Zap70 and provides new mechanistic insights into the non-proteolytic regulation of TCR signaling by E3 ligases.

  13. Dipeptidyl peptidase-4 activity might be a link between tumour necrosis factor alpha and insulin resistance in type 1 diabetes.

    PubMed

    Duvnjak, Lea; Blaslov, Kristina; Perković, Matea Nikolac; Ćuća, Jadranka Knežević

    2016-08-01

    Tumour necrosis factor alpha (TNF α) leads to β cell damage in type 1 diabetes (T1DM) but also causes insulin resistance (IR). It modulates dipeptidyl peptidase-4 (DPP-4) activity, adipokine linked with both IR and T1DM. We were interested if there is an association of TNF α in conjunction with DPP-4 and IR in T1DM. DPP-4 activity, TNF α concentration measurements, and insulin sensitivity calculation using estimated glucose disposal rate (eGDR) equation were performed in 70 T1DM patients. They were divided into two groups according to eGDR median. The group with higher IR had higher value of DPP-4 activity (27.57 ± 1.77 vs. 18.33 ± 1.14, p < 0.001) and TNF α concentration (12.91 ± 0.83 vs. 6.72 ± 0.36, p < 0.001). TNF α concentration and DPP-4 activity negatively correlated with eGDR (r = -0.616, p < 0.001 and r = -0.643, p < 0.001) while correlating positively with each other (r = 0.422; p = 0.001). The linear regression showed that eGDR decreases for 0.166 mg kg(-1) min(-1) by TNF α concentration increase of 1 pg/mL (p < 0.001) and for 0.090 mg kg(-1) min(-1) by DPP-4 activity increase of 1 U/L (p = 0.001) when adjusted for age, gender disease duration, glycated haemoglobin, body mass index and waist-to-hip ratio. eGDR decreased by additional 0.60 mg kg(-1) min(-1) (B = -0.150, p < 0.001) when DPP-4 activity was additionally adjusted for TNF α. TNF α concentration is associated with IR, correlates with its severity and increases the drop in insulin sensitivity modulated by DPP-4 activity. Whether TNF α involvement in the insulin signalling pathway is mediated by DPP-4 activity needs to be further evaluated.

  14. The Brn-2 transcription factor links activated BRAF to melanoma proliferation.

    PubMed

    Goodall, Jane; Wellbrock, Claudia; Dexter, Timothy J; Roberts, Karen; Marais, Richard; Goding, Colin R

    2004-04-01

    Malignant melanoma, an aggressive and increasingly common cancer, is characterized by a strikingly high rate (70%) of mutations in BRAF, a key component of the mitogen-activated protein (MAP) kinase signaling pathway. How signaling events downstream from BRAF affect the underlying program of gene expression is poorly understood. We show that the Brn-2 POU domain transcription factor is highly expressed in melanoma cell lines but not in melanocytes or melanoblasts and that overexpression of Brn-2 in melanocytes results in increased proliferation. Expression of Brn-2 is strongly upregulated by Ras and MAP kinase signaling. Importantly, the Brn-2 promoter is stimulated by kinase-activating BRAF mutants and endogenous Brn-2 expression is inhibited by RNA interference-mediated downregulation of BRAF. Moreover, silent interfering RNA-mediated depletion of Brn-2 in melanoma cells expressing activated BRAF leads to decreased proliferation. The results suggest that the high levels of Brn-2 expression observed in melanomas link BRAF signaling to increased proliferation.

  15. Molecular Links between Caloric Restriction and Sir2/SIRT1 Activation

    PubMed Central

    2014-01-01

    Ageing is the most significant risk factor for a range of prevalent diseases, including cancer, cardiovascular disease, and diabetes. Accordingly, interventions are needed for delaying or preventing disorders associated with the ageing process, i.e., promotion of healthy ageing. Calorie restriction is the only nongenetic and the most robust approach to slow the process of ageing in evolutionarily divergent species, ranging from yeasts, worms, and flies to mammals. Although it has been known for more than 80 years that calorie restriction increases lifespan, a mechanistic understanding of this phenomenon remains elusive. Yeast silent information regulator 2 (Sir2), the founding member of the sirtuin family of protein deacetylases, and its mammalian homologue Sir2-like protein 1 (SIRT1), have been suggested to promote survival and longevity of organisms. SIRT1 exerts protective effects against a number of age-associated disorders. Caloric restriction increases both Sir2 and SIRT1 activity. This review focuses on the mechanistic insights between caloric restriction and Sir2/SIRT1 activation. A number of molecular links, including nicotinamide adenine dinucleotide, nicotinamide, biotin, and related metabolites, are suggested to be the most important conduits mediating caloric restriction-induced Sir2/SIRT1 activation and lifespan extension. PMID:25349818

  16. Sensitivity to food additives, vaso-active amines and salicylates: a review of the evidence.

    PubMed

    Skypala, Isabel J; Williams, M; Reeves, L; Meyer, R; Venter, C

    2015-01-01

    Although there is considerable literature pertaining to IgE and non IgE-mediated food allergy, there is a paucity of information on non-immune mediated reactions to foods, other than metabolic disorders such as lactose intolerance. Food additives and naturally occurring 'food chemicals' have long been reported as having the potential to provoke symptoms in those who are more sensitive to their effects. Diets low in 'food chemicals' gained prominence in the 1970s and 1980s, and their popularity remains, although the evidence of their efficacy is very limited. This review focuses on the available evidence for the role and likely adverse effects of both added and natural 'food chemicals' including benzoate, sulphite, monosodium glutamate, vaso-active or biogenic amines and salicylate. Studies assessing the efficacy of the restriction of these substances in the diet have mainly been undertaken in adults, but the paper will also touch on the use of such diets in children. The difficulty of reviewing the available evidence is that few of the studies have been controlled and, for many, considerable time has elapsed since their publication. Meanwhile dietary patterns and habits have changed hugely in the interim, so the conclusions may not be relevant for our current dietary norms. The conclusion of the review is that there may be some benefit in the removal of an additive or a group of foods high in natural food chemicals from the diet for a limited period for certain individuals, providing the diagnostic pathway is followed and the foods are reintroduced back into the diet to assess for the efficacy of removal. However diets involving the removal of multiple additives and food chemicals have the very great potential to lead to nutritional deficiency especially in the paediatric population. Any dietary intervention, whether for the purposes of diagnosis or management of food allergy or food intolerance, should be adapted to the individual's dietary habits and a suitably

  17. Economic impact of stimulated technological activity. Part 3: Case study, knowledge additions and earth links from space crew systems

    NASA Technical Reports Server (NTRS)

    1971-01-01

    A case study of knowledge contributions from the crew life support aspect of the manned space program is reported. The new information needed to be learned, the solutions developed, and the relation of new knowledge gained to earthly problems were investigated. Illustrations are given in the following categories: supplying atmosphere for spacecraft; providing carbon dioxide removal and recycling; providing contaminant control and removal; maintaining the body's thermal balance; protecting against the space hazards of decompression, radiation, and meteorites; minimizing fire and blast hazards; providing adequate light and conditions for adequate visual performance; providing mobility and work physiology; and providing adequate habitability.

  18. Active metal-matrix composites with embedded smart materials by ultrasonic additive manufacturing

    NASA Astrophysics Data System (ADS)

    Hahnlen, Ryan; Dapino, Marcelo J.

    2010-04-01

    This paper presents the development of active aluminum-matrix composites manufactured by Ultrasonic Additive Manufacturing (UAM), an emerging rapid prototyping process based on ultrasonic metal welding. Composites created through this process experience temperatures as low as 25 °C during fabrication, in contrast to current metal-matrix fabrication processes which require temperatures of 500 °C and above. UAM thus provides unprecedented opportunities to develop adaptive structures with seamlessly embedded smart materials and electronic components without degrading the properties that make these materials and components attractive. This research focuses on developing UAM composites with aluminum matrices and embedded shape memory NiTi, magnetostrictive Galfenol, and electroactive PVDF phases. The research on these composites will focus on: (i) electrical insulation between NiTi and Al phases for strain sensors, investigation and modeling of NiTi-Al composites as tunable stiffness materials and thermally invariant structures based on the shape memory effect; (ii) process development and composite testing for Galfenol-Al composites; and (iii) development of PVDF-Al composites for embedded sensing applications. We demonstrate a method to electrically insulate embedded materials from the UAM matrix, the ability create composites containing up to 22.3% NiTi, and their resulting dimensional stability and thermal actuation characteristics. Also demonstrated is Galfenol-Al composite magnetic actuation of up to 54 μ(see manuscript), and creation of a PVDF-Al composite sensor.

  19. Orientation Control of Block Copolymers Using Surface Active, Phase-Preferential Additives.

    PubMed

    Vora, Ankit; Schmidt, Kristin; Alva, Gabriela; Arellano, Noel; Magbitang, Teddie; Chunder, Anindarupa; Thompson, Leslie E; Lofano, Elizabeth; Pitera, Jed W; Cheng, Joy Y; Sanders, Daniel P

    2016-11-02

    Orientation control of thin film nanostructures derived from block copolymers (BCPs) are of great interest for various emerging technologies like separation membranes, nanopatterning, and energy storage. While many BCP compositions have been developed for these applications, perpendicular orientation of these BCP domains is still very challenging to achieve. Herein we report on a new, integration-friendly approach in which small amounts of a phase-preferential, surface active polymer (SAP) was used as an additive to a polycarbonate-containing BCP formulation to obtain perpendicularly oriented domains with 19 nm natural periodicity upon thermal annealing. In this work, the vertically oriented BCP domains were used to demonstrate next generation patterning applications for advanced semiconductor nodes. Furthermore, these domains were used to demonstrate pattern transfer into a hardmask layer via commonly used etch techniques and graphoepitaxy-based directed self-assembly using existing lithographic integration schemes. We believe that this novel formulation-based approach can easily be extended to other applications beyond nanopatterning.

  20. Performance and modeling of active metal-matrix composites manufactured by ultrasonic additive manufacturing

    NASA Astrophysics Data System (ADS)

    Hahnlen, Ryan; Dapino, Marcelo J.

    2011-04-01

    This paper presents the development and characterization of active aluminum-matrix composites manufactured by Ultrasonic Additive Manufacturing (UAM), an emerging rapid prototyping process based on ultrasonic metal welding. The primary benefit of UAM over other metal-matrix fabrication processes is the low process temperatures, as low as 25 °C. UAM thus provides unprecedented opportunities to develop adaptive structures with seamlessly embedded smart materials and electronic components without degrading the properties that make these materials and components attractive. The objective of this research is to develop UAM composites with aluminum matrices and embedded shape memory NiTi, magnetostrictive Galfenol (FeGa), and polyvinylidene fluoride (PVDF) phases. The paper is focused on the thermally induced strain response and stiffness behavior of NiTi-Al composites, the actuation properties of FeGa-Al composites, and the embedded sensing capabilities of PVDF-Al composites. We observe up to a 10% increase over room temperature stiffness for NiTi-Al composites and a magnetomechanical response in the FeGa-Al composite up to 52.4 μɛ. The response of the PVDF-Al composite to harmonic loads is observed over a frequency range of 10 to 1000 Hz.

  1. Neutrophil proteolytic activation cascades: a possible mechanistic link between chronic periodontitis and coronary heart disease.

    PubMed

    Alfakry, Hatem; Malle, Ernst; Koyani, Chintan N; Pussinen, Pirkko J; Sorsa, Timo

    2016-01-01

    Cardiovascular diseases are chronic inflammatory diseases that affect a large segment of society. Coronary heart disease (CHD), the most common cardiovascular disease, progresses over several years and affects millions of people worldwide. Chronic infections may contribute to the systemic inflammation and enhance the risk for CHD. Periodontitis is one of the most common chronic infections that affects up to 50% of the adult population. Under inflammatory conditions the activation of endogenous degradation pathways mediated by immune responses leads to the release of destructive cellular molecules from both resident and immigrant cells. Matrix metalloproteinases (MMPs) and their regulators can activate each other and play an important role in immune response via degrading extracellular matrix components and modulating cytokines and chemokines. The action of MMPs is required for immigrant cell recruitment at the site of inflammation. Stimulated neutrophils represent the major pathogen-fighting immune cells that upregulate expression of several proteinases and oxidative enzymes, which can degrade extracellular matrix components (e.g. MMP-8, MMP-9 and neutrophil elastase). The activity of MMPs is regulated by endogenous inhibitors and/or candidate MMPs (e.g. MMP-7). The balance between MMPs and their inhibitors is thought to mirror the proteolytic burden. Thus, neutrophil-derived biomarkers, including myeloperoxidase, may activate proteolytic destructive cascades that are involved in subsequent immune-pathological events associated with both periodontitis and CHD. Here, we review the existing studies on the contribution of MMPs and their regulators to the infection-related pathology. Also, we discuss the possible proteolytic involvement and role of neutrophil-derived enzymes as an etiological link between chronic periodontitis and CHD.

  2. Links Between Watershed Activities and the Degradation of Coastal, Tidal Salt Marshes in Southern New England USA

    EPA Science Inventory

    Human activities (e.g., land development, wastewater) in coastal watersheds in New England USA are linked with community- and system-level changes in tidal, organic-rich salt marshes. Significant relationships between various indicators of watershed activities and ecosystem stru...

  3. Assessing Activity Limitations in Patients with Neuromuscular Diseases: Is the ACTIVLIM Questionnaire Linked to ICF and ICF-CY?

    ERIC Educational Resources Information Center

    Raggi, Alberto; Leonardi, Matilde

    2009-01-01

    The objective of this study was to explore to what extent the ACTIVLIM questionnaire, designed to evaluate limitations in activities involving upper and lower limbs in adults and children with neuromuscular diseases, is linked to the domains of the Activities and Participation of the International Classification of Functioning, Disability and…

  4. Framework of Consciousness from Semblance of Activity at Functionally LINKed Postsynaptic Membranes

    PubMed Central

    Vadakkan, Kunjumon I.

    2010-01-01

    Consciousness is seen as a difficult “binding” problem. Binding, a process where different sensations evoked by an item are associated in the nervous system, can be viewed as a process similar to associative learning. Several reports that consciousness is associated with some form of memory imply that different forms of memories have a common feature contributing to consciousness. Based on a proposed synaptic mechanism capable of explaining different forms of memory, we developed a framework for consciousness. It is based on the formation of semblance of sensory stimulus from (1) synaptic semblances when excitatory postsynaptic potentials arrive at functionally LINKed postsynaptic membranes, and (2) network semblances when these potentials summate to elicit action potential initiating activity in a network of neurons. It is then possible to derive a framework for consciousness as a multi-dimensional semblance. According to this framework, a continuum of semblances formed from background sensory stimuli and oscillating neuronal activities serve to maintain consciousness. Feasibility of this framework to explain various physiological and pathological states of consciousness, its subjective nature and qualia is examined. PMID:21833231

  5. Drosophila SAF-B Links the Nuclear Matrix, Chromosomes, and Transcriptional Activity

    PubMed Central

    Alfonso-Parra, Catalina; Maggert, Keith A.

    2010-01-01

    Induction of gene expression is correlated with alterations in nuclear organization, including proximity to other active genes, to the nuclear cortex, and to cytologically distinct domains of the nucleus. Chromosomes are tethered to the insoluble nuclear scaffold/matrix through interaction with Scaffold/Matrix Attachment Region (SAR/MAR) binding proteins. Identification and characterization of proteins involved in establishing or maintaining chromosome-scaffold interactions is necessary to understand how the nucleus is organized and how dynamic changes in attachment are correlated with alterations in gene expression. We identified and characterized one such scaffold attachment factor, a Drosophila homolog of mammalian SAF-B. The large nuclei and chromosomes of Drosophila have allowed us to show that SAF-B inhabits distinct subnuclear compartments, forms weblike continua in nuclei of salivary glands, and interacts with discrete chromosomal loci in interphase nuclei. These interactions appear mediated either by DNA-protein interactions, or through RNA-protein interactions that can be altered during changes in gene expression programs. Extraction of soluble nuclear proteins and DNA leaves SAF-B intact, showing that this scaffold/matrix-attachment protein is a durable component of the nuclear matrix. Together, we have shown that SAF-B links the nuclear scaffold, chromosomes, and transcriptional activity. PMID:20422039

  6. Variable expression of activation-linked surface antigens on human mast cells in health and disease.

    PubMed

    Valent, P; Schernthaner, G H; Sperr, W R; Fritsch, G; Agis, H; Willheim, M; Bühring, H J; Orfao, A; Escribano, L

    2001-02-01

    Mast cells (MC) are multipotent effector cells of the immune system. They contain an array of biologically active mediator substances in their granules. MC also express a number of functionally important cell surface antigens, including stem cell factor receptor (SCFR=kit=CD117), high affinity IgER (FcepsilonRI), or CSaR (CD88). Respective ligands can induce or promote degranulation, migration, or cytokine production. Other integral surface molecules can mediate adhesion or cell aggregation. Recent data suggest that a number of critical molecules are variably expressed on the surface of human MC. In fact, depending on the environment (organ), stage of cell maturation, type of disease, and other factors, MC express variable amounts of activation-linked antigens (CD25, CD63, CD69, CD88), cell recognition molecules (CD2, CD11, CD18, CD50, CD54), or cytokine receptors. At present, however, little is known about the mechanisms and regulation of expression of such antigens. The present article gives an overview of MC phenotypes in health and disease, and attempts to provide explanations for the phenotypic variability of MC.

  7. Linking obesity and activity level with children's television and video game use.

    PubMed

    Vandewater, Elizabeth A; Shim, Mi-suk; Caplovitz, Allison G

    2004-02-01

    This study examined the links between childhood obesity, activity participation and television and video game use in a nationally representative sample of children (N = 2831) ages 1-12 using age-normed body mass index (BMI) ratings. Results indicated that while television use was not related to children's weight status, video game use was. Children with higher weight status played moderate amounts of electronic games, while children with lower weight status played either very little or a lot of electronic games. Interaction analyses revealed that this curvilinear relationship applied to children under age 8 and that girls, but not boys, with higher weight status played more video games. Children ages 9-12 with lower weight status used the computer (non-game) for moderate amounts of time, while those with higher weight status used the computer either very little or a lot. This was also true for the relationship between print use and weight status for children of all ages. Results also indicated that children with higher weight status spent more time in sedentary activities than those with lower weight status.

  8. p53 oligomerization and DNA looping are linked with transcriptional activation.

    PubMed Central

    Stenger, J E; Tegtmeyer, P; Mayr, G A; Reed, M; Wang, Y; Wang, P; Hough, P V; Mastrangelo, I A

    1994-01-01

    We examined the role of p53 oligomerization in DNA binding and in transactivation. By conventional electron microscopy (EM) and scanning transmission EM, we find that wild-type tetramers contact 18-20 bp at single or tandem 19 bp consensus sequences and also stack in apparent register, tetramer on top of tetramer. Stacked tetramers link separated DNA binding sites with DNA loops. Interestingly, the p53(1-320) segment, which lacks the C-terminal tetramerization domain, binds DNA consensus sites as stacked oligomers. Although the truncated protein binds DNA with reduced efficiency, it nevertheless induces DNA looping by self-association. p53, therefore, has a C-terminal tetramerization domain that enhances DNA binding and a non-tetrameric oligomerization domain that stacks p53 at consensus sites and loops separated consensus sites via protein-protein interactions. Using model promoters, we demonstrate that wild-type and tetramerization-deficient p53s activate transcription well when tandem consensus sites are proximal to TATA sequences and poorly when tandem sites are distal. In the presence of proximal sites, however, stimulation by distal sites increases 25-fold. Tetramerization and stacking of tetramers, therefore, provide dual mechanisms to augment the number of p53 molecules available for activation through p53 response elements. DNA looping between separated response elements further increases the concentration of local p53 by translocating distally bound protein to the promoter. Images PMID:7813439

  9. Who is good at this game? Linking an activity to a social category undermines children's achievement.

    PubMed

    Cimpian, Andrei; Mu, Yan; Erickson, Lucy C

    2012-05-01

    Children's achievement-related theories have a profound impact on their academic success. Children who adopt entity theories believe that their ability to perform a task is dictated by the amount of natural talent they possess for that task--a belief that has well-documented adverse consequences for their achievement (e.g., lowered persistence, impaired performance). It is thus important to understand what leads children to adopt entity theories. In the experiments reported here, we hypothesized that the mere act of linking success at an unfamiliar, challenging activity to a social group gives rise to entity beliefs that are so powerful as to interfere with children's ability to perform the activity. Two experiments showed that, as predicted, the performance of 4- to 7-year-olds (N = 192) was impaired by exposure to information that associated success in the task at hand with membership in a certain social group (e.g., "boys are good at this game"), regardless of whether the children themselves belonged to that group.

  10. Resveratrol cross-linked chitosan loaded with phospholipid for controlled release and antioxidant activity.

    PubMed

    Jeong, Hun; Samdani, Kunda J; Yoo, Dong Hyuck; Lee, Dong Won; Kim, Nam Hoon; Yoo, Il-Soo; Lee, Joong Hee

    2016-12-01

    Despite the therapeutic effects of resveratrol, its clinical application is restricted by its poor oral bioavailability and low water solubility. To overcome these physicochemical and pharmacokinetic limitations, encapsulation of resveratrol (RV) into nanodevices has been explored. Resveratrol cross-linked chitosan nanoparticles modified with phospholipids (RVC-lipid) were synthesized using a double emulsion technique. The surface morphology of RVC-lipid nanoparticles was evaluated with field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). Particle size was measured using dynamic light scattering technique (DLS), X-ray diffraction (XRD) was performed to identify the crystallographic nature and Fourier transform infrared spectroscopy (FTIR) was used to measure changes in the chemical structures of the resveratrol and RVC-lipid nanoparticles. Results showed RVC-lipid nanoparticle had a characteristic amorphous structure, a mean particle sizes of 570nm in DI water and 950nm in ethanol, and an encapsulation efficiency of 63.82% in aqueous medium and 85.59% in ethanol medium. In-vitro release studies demonstrated a slow and sustained release of resveratrol governed by diffusion. Based on assays of antioxidant activity the scavenging activity of RVC-lipid nanoparticles was inferior to that of resveratrol due to its prolonged release. We concluded that phospholipids are the potential carriers for resveratrol.

  11. Links between Osteoarthritis and Diabetes:Implications for Management from a Physical Activity Perspective

    PubMed Central

    Piva, Sara R.; Susko, Allyn M.; Khoja, Samannaaz S.; Josbeno, Deborah A.; Fitzgerald, G. Kelley; Toledo, Frederico G. S.

    2014-01-01

    SYNOPSIS Osteoarthritis (OA) and type 2 diabetes mellitus (T2DM) often co-exist in older adults. There is increased susceptibility to develop arthritis in those with T2DM, which is supported by observations of higher prevalence of arthritis in those with T2DM (52%) compared to those without it (27%). The association between OA and T2DM has been traditionally attributed to underlying shared risk factors of age and obesity. Emerging evidence suggests that alterations in lipid metabolism and hyperglycemia might have a direct impact on cartilage health and subchondral bone that contribute to the development and/or progression of OA. Adequate management of older persons with both OA and T2DM benefits from a comprehensive understanding of the risk factors associated with these diseases. In this review, we discuss common risk factors and emerging underlying links between OA and T2DM, and emphasize the importance of physical activity to improve metabolism and decrease disability and pain in this population. Implications for safe and effective physical activity approaches in older patients with OA and T2DM are also discussed. PMID:25453302

  12. 75 FR 77645 - Agency Information Collection Activities; Proposed Collection; Comment Request; Color Additive...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-13

    ... Collection; Comment Request; Color Additive Certification Requests and Recordkeeping AGENCY: Food and Drug... certification of color additives manufactured for use in foods, drugs, cosmetics or medical devices in the... of information technology. Color Additive Certification Requests and Recordkeeping--21 CFR Part...

  13. Additives-biological activities of tin-containing polymers bonded to noncarbons

    SciTech Connect

    Carraher, C.; Butler, C.; Foster, V.; Pandya, B.; Sterling, D.

    1993-12-31

    Organotin-containing polymers serve as effective additives to a silicon-based sealant, latex coating and talc exhibiting inhibition to tested bacteria and fungi. These polymers are candidates for uses a paint additives, sealant and caulk additives and within talc as an epidermal treatment.

  14. Community Links

    ERIC Educational Resources Information Center

    Nelson, Mary

    1975-01-01

    At Moraine Valley Community College (Illinois), a chain of events, programs, activities, and services has linked the college and community in such areas as fine arts, ethnic groups, public services, community action, community service, and community education. (Author/NHM)

  15. The link in Linking

    PubMed Central

    Caldwell, Jane C; Chiale, Pablo A; Gonzalez, Mario D; Baranchuk, Adrian

    2013-01-01

    We present 2 cases of the slow-fast form of AVNRT with initially narrow QRS complexes followed by sudden unexpected transition to persistently wide QRS complexes due to aberrant intraventricular conduction. Introduction of a properly timed extrastimulus in one case and critical oscillations in cycle length due to short-long coupling in the second case set the stage for the initial bundle branch block. However, persistence of the aberrancy pattern once the initial event abated was maintained by the "linking" phenomenon. Delayed, retrograde concealed activation from the contralateral bundle branch perpetuated the initial bundle branch block. PMID:23840106

  16. The link in Linking.

    PubMed

    Caldwell, Jane C; Chiale, Pablo A; Gonzalez, Mario D; Baranchuk, Adrian

    2013-05-01

    We present 2 cases of the slow-fast form of AVNRT with initially narrow QRS complexes followed by sudden unexpected transition to persistently wide QRS complexes due to aberrant intraventricular conduction. Introduction of a properly timed extrastimulus in one case and critical oscillations in cycle length due to short-long coupling in the second case set the stage for the initial bundle branch block. However, persistence of the aberrancy pattern once the initial event abated was maintained by the "linking" phenomenon. Delayed, retrograde concealed activation from the contralateral bundle branch perpetuated the initial bundle branch block.

  17. Muscle activation patterns are bilaterally linked during split-belt treadmill walking in humans

    PubMed Central

    Ivanenko, Y. P.; Massaad, F.; Bruijn, S. M.; Duysens, J.; Lacquaniti, F.

    2014-01-01

    There is growing evidence that human locomotion is controlled by flexibly combining a set of basic muscle activity patterns. To explore how these patterns are modified to cope with environmental constraints, 10 healthy young adults 1st walked on a split-belt treadmill at symmetric speeds of 4 and 6 km/h for 2 min. An asymmetric condition was then performed for 10 min in which treadmill speeds for the dominant (fast) and nondominant (slow) sides were 6 and 4 km/h, respectively. This was immediately followed by a symmetric speed condition of 4 km/h for 5 min. Gait kinematics and ground reaction forces were recorded. Electromyography (EMG) was collected from 12 lower limb muscles on each side of the body. Nonnegative matrix factorization was applied to the EMG signals bilaterally and unilaterally to obtain basic activation patterns. A cross-correlation analysis was then used to quantify temporal changes in the activation patterns. During the early (1st 10 strides) and late (final 10 strides) phases of the asymmetric condition, the patterns related to ankle plantar flexor (push-off) of the fast limb and quadriceps muscle (contralateral heel contact) of the slow limb occurred earlier in the gait cycle compared with the symmetric conditions. Moreover, a bilateral temporal alignment of basic patterns between limbs was still maintained in the split-belt condition since a similar shift was observed in the unilateral patterns. The results suggest that the temporal structure of these locomotor patterns is shaped by sensory feedback and that the patterns are bilaterally linked. PMID:24478155

  18. Linking human brain local activity fluctuations to structural and functional network architectures

    PubMed Central

    Baria, A.T.; Mansour, A.; Huang, L.; Baliki, M.N.; Cecchi, G.A.; Mesulam, M.M.; Apkarian, A.V.

    2013-01-01

    Activity of cortical local neuronal populations fluctuates continuously, and a large proportion of these fluctuations are shared across populations of neurons. Here we seek organizational rules that link these two phenomena. Using neuronal activity, as identified by functional MRI (fMRI) and for a given voxel or brain region, we derive a single measure of full bandwidth brain-oxygenation-level-dependent (BOLD) fluctuations by calculating the slope, α, for the log-linear power spectrum. For the same voxel or region, we also measure the temporal coherence of its fluctuations to other voxels or regions, based on exceeding a given threshold, Θ, for zero lag correlation, establishing functional connectivity between pairs of neuronal populations. From resting state fMRI, we calculated whole-brain group-averaged maps for α and for functional connectivity. Both maps showed similar spatial organization, with a correlation coefficient of 0.75 between the two parameters across all brain voxels, as well as variability with hodology. A computational model replicated the main results, suggesting that synaptic low-pass filtering can account for these interrelationships. We also investigated the relationship between α and structural connectivity, as determined by diffusion tensor imaging-based tractography. We observe that the correlation between α and connectivity depends on attentional state; specifically, α correlated more highly to structural connectivity during rest than while attending to a task. Overall, these results provide global rules for the dynamics between frequency characteristics of local brain activity and the architecture of underlying brain networks. PMID:23396160

  19. Spectrum of X-linked hydrocephalus (HSAS), MASA syndrome, and complicated spastic paraplegia (SPG1): Clincal review with six additional families

    SciTech Connect

    Schrander-Stumpel, C.; Hoeweler, C.; Jones, M.

    1995-05-22

    X-linked hydrocephalus (HSAS) (MIM{sup *}307000), MASA syndrome (MIM {sup *}303350), and complicated spastic paraplegia (SPG1) (MIM {sup *}3129000) are closely related. Soon after delineation, SPG1 was incorporated into the spectrum of MASA syndrome. HSAS and MASA syndrome show great clinical overlap; DNA linkage analysis places the loci at Xq28. In an increasing number of families with MASA syndrome or HSAS, mutations in L1CAM, a gene located at Xq28, have been reported. In order to further delineate the clinical spectrum, we studied 6 families with male patients presenting with MASA syndrome, HSAS, or a mixed phenotype. We summarized data from previous reports and compared them with our data. Clinical variability appears to be great, even within families. Problems in genetic counseling and prenatal diagnosis, the possible overlap with X-linked corpus callosum agenesis and FG syndrome, and the different forms of X-linked complicated spastic paraplegia are discussed. Since adducted thumbs and spastic paraplegia are found in 90% of the patients, the condition may be present in males with nonspecific mental retardation. We propose to abandon the designation MASA syndrome and use the term HSAS/MASA spectrum, incorporating SPG1. 79 refs., 6 figs., 2 tabs.

  20. Suppression of Dendritic Cell Activation by Diabetes Autoantigens Linked to the Cholera Toxin B Subunit

    PubMed Central

    Odumosu, Oludare; Payne, Kimberly; Baez, Mavely; Jutzy, Jessica; Wall, Nathan; Langridge, William

    2010-01-01

    Antigen presenting cells, specifically dendritic cells (DCs) are a focal point in the delicate balance between T cell tolerance and immune responses contributing to the onset of type I diabetes (T1D). Weak adjuvant proteins like the cholera toxin B subunit when linked to autoantigens may sufficiently alter the balance of this initial immune response to suppress the development of autoimmunity. To assess adjuvant enhancement of autoantigen mediated immune suppression of Type 1 diabetes, we examined the cholera toxin B subunit (CTB)-proinsulin fusion protein (CTB-INS) activation of immature dendritic cells (iDC) at the earliest detectable stage of the human immune response. In this study, Incubation of human umbilical cord blood monocyte-derived immature DCs with CTB-INS autoantigen fusion protein increased the surface membrane expression of DC toll-like receptor (TLR-2) while no significant upregulation in TLR-4 expression was detected. Inoculation of iDCs with CTB stimulated the biosynthesis of both CD86 and CD83 co-stimulatory factors demonstrating an immunostimulatory role for CTB in both DC activation and maturation. In contrast, incubation of iDCs with proinsulin partially suppressed CD86 co-stimulatory factor mediated DC activation, while incubation of iDCs with CTB-INS fusion protein completely suppressed iDC biosynthesis of both CD86 and CD83 costimulatory factors. The incubation of iDCs with increasing amounts of insulin did not increase the level of immune suppression but rather activated DC maturation by stimulating increased biosynthesis of both CD86 and CD83 costimulatory factors. Inoculation of iDCs with CTB-INS fusion protein dramatically increased secretion of the immunosuppressive cytokine IL-10 and suppressed synthesis of the pro-inflammatory cytokine IL12/23 p40 subunit protein suggesting that linkage of CTB to insulin (INS) may play an important role in mediating DC guidance of cognate naïve Th0 cell development into immunosuppressive T

  1. Properties of collagen gels cross-linked by N-hydroxysuccinimide activated adipic acid deriviate.

    PubMed

    Duan, Lian; Liu, Wentao; Tian, Zhenhua; Li, Conghu; Li, Guoying

    2014-08-01

    In order to improve the properties of collagen gel, N-hydroxysuccinimide activated adipic acid derivative (NHS-AA) was introduced into the formation of collagen fibrils. NHS-AA with different [NHS-AA]/[NH2] ratios (0.1-1.5, calculated by [ester group] of NHS-AA and [NH2] of lysine and hydroxylysine residues of collagen) was added after, simultaneously with or before the formation of collagen fibrils (abbreviated CAF, CSF and CBF, respectively) to obtain different collagen gels. With the same dose of NHS-AA, the cross-linking degree for CAF was lower than those for CSF and CBF. The formation of collagen fibrils was restrained by NHS-AA for CSF and CBF while that for CAF was unaffected. When the dose of NHS-AA increased from 0.1 to 1.5, the water contents of CSF and CBF increased while that of CAF had no obvious change. With lower dose of NHS-AA (0.1), CAF possessed higher value of G' (87.3Pa) and the best thermal stability (47.6°C). As the ratio of [NHS-AA]/[NH2] increased to 1.5, CSF had the maximum value of G' (288.8Pa) and CAF had the best thermal stability (52.9°C). These results showed collagen gels with different properties could be prepared by adding NHS-AA with different adding sequence and dose.

  2. A Novel Topology Link-Controlling Approach for Active Defense of a Node in a Network.

    PubMed

    Li, Jun; Hu, HanPing; Ke, Qiao; Xiong, Naixue

    2017-03-09

    With the rapid development of virtual machine technology and cloud computing, distributed denial of service (DDoS) attacks, or some peak traffic, poses a great threat to the security of the network. In this paper, a novel topology link control technique and mitigation attacks in real-time environments is proposed. Firstly, a non-invasive method of deploying virtual sensors in the nodes is built, which uses the resource manager of each monitored node as a sensor. Secondly, a general topology-controlling approach of resisting the tolerant invasion is proposed. In the proposed approach, a prediction model is constructed by using copula functions for predicting the peak of a resource through another resource. The result of prediction determines whether or not to initiate the active defense. Finally, a minority game with incomplete strategy is employed to suppress attack flows and improve the permeability of the normal flows. The simulation results show that the proposed approach is very effective in protecting nodes.

  3. Linker Immolation Determines Cell Killing Activity of Disulfide-Linked Pyrrolobenzodiazepine Antibody-Drug Conjugates.

    PubMed

    Zhang, Donglu; Pillow, Thomas H; Ma, Yong; Cruz-Chuh, Josefa Dela; Kozak, Katherine R; Sadowsky, Jack D; Lewis Phillips, Gail D; Guo, Jun; Darwish, Martine; Fan, Peter; Chen, Jingtian; He, Changrong; Wang, Tao; Yao, Hui; Xu, Zijin; Chen, Jinhua; Wai, John; Pei, Zhonghua; Hop, Cornelis E C A; Khojasteh, S Cyrus; Dragovich, Peter S

    2016-11-10

    Disulfide bonds could be valuable linkers for a variety of therapeutic applications requiring tunable cleavage between two parts of a molecule (e.g., antibody-drug conjugates). The in vitro linker immolation of β-mercaptoethyl-carbamate disulfides and DNA alkylation properties of associated payloads were investigated to understand the determinant of cell killing potency of anti-CD22 linked pyrrolobenzodiazepine (PBD-dimer) conjugates. Efficient immolation and release of a PBD-dimer with strong DNA alkylation properties were observed following disulfide cleavage of methyl- and cyclobutyl-substituted disulfide linkers. However, the analogous cyclopropyl-containing linker did not immolate, and the associated thiol-containing product was a poor DNA alkylator. As predicted from these in vitro assessments, the related anti-CD22 ADCs showed different target-dependent cell killing activities in WSU-DLCL2 and BJAB cell lines. These results demonstrate how the in vitro immolation models can be used to help design efficacious ADCs.

  4. A Novel Topology Link-Controlling Approach for Active Defense of Nodes in Networks

    PubMed Central

    Li, Jun; Hu, HanPing; Ke, Qiao; Xiong, Naixue

    2017-01-01

    With the rapid development of virtual machine technology and cloud computing, distributed denial of service (DDoS) attacks, or some peak traffic, poses a great threat to the security of the network. In this paper, a novel topology link control technique and mitigation attacks in real-time environments is proposed. Firstly, a non-invasive method of deploying virtual sensors in the nodes is built, which uses the resource manager of each monitored node as a sensor. Secondly, a general topology-controlling approach of resisting the tolerant invasion is proposed. In the proposed approach, a prediction model is constructed by using copula functions for predicting the peak of a resource through another resource. The result of prediction determines whether or not to initiate the active defense. Finally, a minority game with incomplete strategy is employed to suppress attack flows and improve the permeability of the normal flows. The simulation results show that the proposed approach is very effective in protecting nodes. PMID:28282962

  5. Enhancing the Curriculum through the Addition of Rich and Diverse Language Development Activities.

    ERIC Educational Resources Information Center

    Anen, Judith

    The primary goal of this practicum was to provide opportunities for rich and diverse language activities designed to enhance the kindergarten curriculum. New instructional guidelines were designed that encouraged daily classroom time devoted to language development activities. These activities replaced all formal isolated skill instruction.…

  6. A PHYSICAL LINK BETWEEN JET FORMATION AND HOT PLASMA IN ACTIVE GALACTIC NUCLEI

    SciTech Connect

    Wu Qingwen; Wang Dingxiong; Cao Xinwu; Ho, Luis C. E-mail: dxwang@hust.edu.cn E-mail: lho@obs.carnegiescience.edu

    2013-06-10

    Recent observations suggest that in black hole X-ray binaries jet/outflow formation is related to the hot plasma in the vicinity of the black hole, either in the form of an advection-dominated accretion flow at low accretion rates or in a disk corona at high accretion rates. We test the viability of this scenario for supermassive black holes using two samples of active galactic nuclei distinguished by the presence (radio-strong) and absence (radio-weak) of well-collimated, relativistic jets. Each is centered on a narrow range of black hole mass but spans a very broad range of Eddington ratios, effectively simulating in a statistical manner the behavior of a single black hole evolving across a wide spread in accretion states. Unlike the relationship between the radio and optical luminosity, which shows an abrupt break between high- and low-luminosity sources at an Eddington ratio of {approx}1%, the radio emission-a measure of the jet power-varies continuously with the hard X-ray (2-10 keV) luminosity, roughly as L{sub R} {proportional_to} L{sub X}{sup 0.6-0.75}. This relation, which holds for both radio-weak and radio-strong active galaxies, is similar to the one seen in X-ray binaries. Jet/outflow formation appears to be closely linked to the conditions that give rise to the hot, optically thin coronal emission associated with accretion flows, both in the regime of low and high accretion rates.

  7. A Physical Link between Jet Formation and Hot Plasma in Active Galactic Nuclei

    NASA Astrophysics Data System (ADS)

    Wu, Qingwen; Cao, Xinwu; Ho, Luis C.; Wang, Ding-Xiong

    2013-06-01

    Recent observations suggest that in black hole X-ray binaries jet/outflow formation is related to the hot plasma in the vicinity of the black hole, either in the form of an advection-dominated accretion flow at low accretion rates or in a disk corona at high accretion rates. We test the viability of this scenario for supermassive black holes using two samples of active galactic nuclei distinguished by the presence (radio-strong) and absence (radio-weak) of well-collimated, relativistic jets. Each is centered on a narrow range of black hole mass but spans a very broad range of Eddington ratios, effectively simulating in a statistical manner the behavior of a single black hole evolving across a wide spread in accretion states. Unlike the relationship between the radio and optical luminosity, which shows an abrupt break between high- and low-luminosity sources at an Eddington ratio of ~1%, the radio emission—a measure of the jet power—varies continuously with the hard X-ray (2-10 keV) luminosity, roughly as L_R \\propto L_X^{0.6{--}0.75}. This relation, which holds for both radio-weak and radio-strong active galaxies, is similar to the one seen in X-ray binaries. Jet/outflow formation appears to be closely linked to the conditions that give rise to the hot, optically thin coronal emission associated with accretion flows, both in the regime of low and high accretion rates.

  8. DOD Financial Management: Additional Efforts Needed to Improve Audit Readiness of Navy Military Pay and Other Related Activities

    DTIC Science & Technology

    2015-09-01

    DOD FINANCIAL MANAGEMENT Additional Efforts Needed to Improve Audit Readiness of Navy Military Pay and Other Related...REPORT TYPE 3. DATES COVERED 00-00-2015 to 00-00-2015 4. TITLE AND SUBTITLE DOD Financial Management: Additional Efforts Needed to Improve Audit ...Additional Efforts Needed to Improve Audit Readiness of Navy Military Pay and Other Related Activities Why GAO Did This Study DOD continues to work

  9. 40 CFR 260.40 - Additional regulation of certain hazardous waste recycling activities on a case-by-case basis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 27 2012-07-01 2012-07-01 false Additional regulation of certain hazardous waste recycling activities on a case-by-case basis. 260.40 Section 260.40 Protection of... SYSTEM: GENERAL Rulemaking Petitions § 260.40 Additional regulation of certain hazardous waste...

  10. 40 CFR 260.40 - Additional regulation of certain hazardous waste recycling activities on a case-by-case basis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 27 2013-07-01 2013-07-01 false Additional regulation of certain hazardous waste recycling activities on a case-by-case basis. 260.40 Section 260.40 Protection of... SYSTEM: GENERAL Rulemaking Petitions § 260.40 Additional regulation of certain hazardous waste...

  11. 40 CFR 260.40 - Additional regulation of certain hazardous waste recycling activities on a case-by-case basis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Additional regulation of certain hazardous waste recycling activities on a case-by-case basis. 260.40 Section 260.40 Protection of... SYSTEM: GENERAL Rulemaking Petitions § 260.40 Additional regulation of certain hazardous waste...

  12. 40 CFR 260.40 - Additional regulation of certain hazardous waste recycling activities on a case-by-case basis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Additional regulation of certain hazardous waste recycling activities on a case-by-case basis. 260.40 Section 260.40 Protection of... SYSTEM: GENERAL Rulemaking Petitions § 260.40 Additional regulation of certain hazardous waste...

  13. 40 CFR 260.40 - Additional regulation of certain hazardous waste recycling activities on a case-by-case basis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Additional regulation of certain hazardous waste recycling activities on a case-by-case basis. 260.40 Section 260.40 Protection of... SYSTEM: GENERAL Rulemaking Petitions § 260.40 Additional regulation of certain hazardous waste...

  14. CYLD, a deubiquitinase specific for lysine63-linked polyubiquitins, accumulates at the postsynaptic density in an activity-dependent manner

    SciTech Connect

    Dosemeci, Ayse; Thein, Soe; Yang, Yijung; Reese, Thomas S.; Tao-Cheng, Jung-Hwa

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer CYLD is a deubiquitinase specific for lysine63-linked polyubiquitins. Black-Right-Pointing-Pointer Presence of CYLD in PSDs is established by biochemistry and immunoEM. Black-Right-Pointing-Pointer CYLD accumulates on PSDs upon depolarization of neurons. Black-Right-Pointing-Pointer Accumulation of CYLD at PSDs may regulate trafficking/degradation of synaptic proteins. -- Abstract: Polyubiquitin chains on proteins flag them for distinct fates depending on the type of polyubiquitin linkage. While lysine48-linked polyubiquitination directs proteins to proteasomal degradation, lysine63-linked polyubiquitination promotes different protein trafficking and is involved in autophagy. Here we show that postsynaptic density (PSD) fractions from adult rat brain contain deubiquitinase activity that targets both lysine48 and lysine63-linked polyubiquitins. Comparison of PSD fractions with parent subcellular fractions by Western immunoblotting reveals that CYLD, a deubiquitinase specific for lysine63-linked polyubiquitins, is highly enriched in the PSD fraction. Electron microscopic examination of hippocampal neurons in culture under basal conditions shows immunogold label for CYLD at the PSD complex in approximately one in four synapses. Following depolarization by exposure to high K+, the proportion of CYLD-labeled PSDs as well as the labeling intensity of CYLD at the PSD increased by more than eighty percent, indicating that neuronal activity promotes accumulation of CYLD at the PSD. An increase in postsynaptic CYLD following activity would promote removal of lysine63-polyubiquitins from PSD proteins and thus could regulate their trafficking and prevent their autophagic degradation.

  15. Exposure to high glutamate concentration activates aerobic glycolysis but inhibits ATP-linked respiration in cultured cortical astrocytes.

    PubMed

    Shen, Yao; Tian, Yueyang; Shi, Xiaojie; Yang, Jianbo; Ouyang, Li; Gao, Jieqiong; Lu, Jianxin

    2014-08-01

    Astrocytes play a key role in removing the synaptically released glutamate from the extracellular space and maintaining the glutamate below neurotoxic level in the brain. However, high concentration of glutamate leads to toxicity in astrocytes, and the underlying mechanisms are unclear. The purpose of this study was to investigate whether energy metabolism disorder, especially impairment of mitochondrial respiration, is involved in the glutamate-induced gliotoxicity. Exposure to 10-mM glutamate for 48 h stimulated glycolysis and respiration in astrocytes. However, the increased oxygen consumption was used for proton leak and non-mitochondrial respiration, but not for oxidative phosphorylation and ATP generation. When the exposure time extended to 72 h, glycolysis was still activated for ATP generation, but the mitochondrial ATP-linked respiration of astrocytes was reduced. The glutamate-induced astrocyte damage can be mimicked by the non-metabolized substrate d-aspartate but reversed by the non-selective glutamate transporter inhibitor TBOA. In addition, the glutamate toxicity can be partially reversed by vitamin E. These findings demonstrate that changes of bioenergetic profile occur in cultured cortical astrocytes exposed to high concentration of glutamate and highlight the role of mitochondria respiration in glutamate-induced gliotoxicity in cortical astrocytes.

  16. Chromatographic isolation of the functionally active MutS protein covalently linked to deoxyribonucleic acid.

    PubMed

    Monakhova, Mayya; Ryazanova, Alexandra; Hentschel, Andreas; Viryasov, Mikhail; Oretskaya, Tatiana; Friedhoff, Peter; Kubareva, Elena

    2015-04-10

    DNA metabolism is based on formation of different DNA-protein complexes which can adopt various conformations. To characterize functioning of such complexes, one needs a solution-based technique which allows fixing a complex in a certain transient conformation. The crosslinking approach is a popular tool for such studies. However, it is under debate if the protein components retain their natural activities in the resulting crosslinked complexes. In the present work we demonstrate the possibility of obtaining pure DNA conjugate with functionally active protein using as example MutS protein from Escherichia coli mismatch repair system. A conjugate of a chemically modified mismatch-containing DNA duplex with MutS is fixed by thiol-disulfide exchange reaction. To perform a reliable test of the protein activity in the conjugate, such conjugate must be thoroughly separated from the uncrosslinked protein and DNA prior to the test. In the present work, we employ anion exchange chromatography for this purpose for the first time and demonstrate this technique to be optimal for the conjugate purification. The activity test is a FRET-based detection of DNA unbending. We show experimentally that MutS in the conjugate retains its ability to unbend DNA in response to ATP addition and find out for the first time that the DNA unbending rate increases with increasing ATP concentration. Since the crosslinked complexes contain active MutS protein, they can be used in further experiments to investigate MutS interactions with other proteins of the mismatch repair system.

  17. Syntheses, cytotoxic activity evaluation and HQSAR study of 1,2,3-triazole-linked isosteviol derivatives as potential anticancer agents.

    PubMed

    Liu, Cong-Jun; Liu, Yan-Ping; Yu, Shu-Ling; Dai, Xing-Jie; Zhang, Tao; Tao, Jing-Chao

    2016-11-15

    A series of novel 1,2,3-triazole-linked isosteviol derivatives were designed and synthesized via Huisgen-click reaction. Their cytotoxicities in vitro against HCT-116 and JEKO-1 cells were screened. The preliminary bioassays indicated that most of the title compounds exhibited noteworthy cytotoxic activities. Particularly, the compound 10b revealed the most potent inhibitory activities against HCT-116 cells with IC50 value of 2.987±0.098μM, which was better than that (3.906±0.261μM) of positive control cisplatin. On the basis of these bioactivity data, hologram quantitative structure-activity relationship (HQSAR) was performed, and a statistically reliable model with good predictive power (r(2)=0.848, q(2)=0.544 and R(2)pred=0.982) was achieved. Additionally, the contribution maps derived from the optimal model explained the individual atomic contributions to the activity for each molecule.

  18. 34 CFR 412.30 - What additional activities must be carried out by Curriculum Coordination Centers?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... activities: (a) Assist States in the development, adaptation, adoption, dissemination, and use of curriculum... regional CCC meetings; and (7) Fostering adoption and adaptations of materials available through the...

  19. 34 CFR 412.30 - What additional activities must be carried out by Curriculum Coordination Centers?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... activities: (a) Assist States in the development, adaptation, adoption, dissemination, and use of curriculum... regional CCC meetings; and (7) Fostering adoption and adaptations of materials available through the...

  20. 34 CFR 412.30 - What additional activities must be carried out by Curriculum Coordination Centers?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... activities: (a) Assist States in the development, adaptation, adoption, dissemination, and use of curriculum... regional CCC meetings; and (7) Fostering adoption and adaptations of materials available through the...

  1. 34 CFR 412.30 - What additional activities must be carried out by Curriculum Coordination Centers?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... activities: (a) Assist States in the development, adaptation, adoption, dissemination, and use of curriculum... regional CCC meetings; and (7) Fostering adoption and adaptations of materials available through the...

  2. 34 CFR 412.30 - What additional activities must be carried out by Curriculum Coordination Centers?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... activities: (a) Assist States in the development, adaptation, adoption, dissemination, and use of curriculum... regional CCC meetings; and (7) Fostering adoption and adaptations of materials available through the...

  3. Investigating Possible Links between Incoming Cosmic Ray Fluxes and Lightning Activity

    NASA Astrophysics Data System (ADS)

    Chronis, Themis

    2010-05-01

    During the past two decades, particular scientific attention has been drawn to the potential cosmic ray-atmospheric coupling. Galactic cosmic rays reaching the upper troposphere are suggested as the key modulators of the global electric circuit with further implications on cloud microphysical processes. Unfortunately, the scarcity of the associated observations renders the evaluation of the theoritized mechanisms rather difficult. This contribution proposes a different approach by introducing observations provided by the National Lightning Detection Network for the period 1990-2005. The study area encompasses the greater part of continental U.S. and the surrounding waters. The results highlight a statistically significant positive trend between monthly lightning activity and galactic cosmic ray fluxes during the winter season. During the summer season the trend becomes statistically non-significant. In addition, the featured analysis introduces a technique to assess the potential impact of Forbush Events on daily lightning activity. Results illustrate that lightning activity may be responsive (minimized) 4-5 days following a Forbush Event.

  4. Valuation of OSA process and folic acid addition as excess sludge minimization alternatives applied in the activated sludge process.

    PubMed

    Martins, C L; Velho, V F; Ramos, S R A; Pires, A S C D; Duarte, E C N F A; Costa, R H R

    2016-01-01

    The aim of this study was to investigate the ability of the oxic-settling-anaerobic (OSA)-process and the folic acid addition applied in the activated sludge process to reduce the excess sludge production. The study was monitored during two distinct periods: activated sludge system with OSA-process, and activated sludge system with folic acid addition. The observed sludge yields (Yobs) were 0.30 and 0.08 kgTSS kg(-1) chemical oxygen demand (COD), control phase and OSA-process (period 1); 0.33 and 0.18 kgTSS kg(-1) COD, control phase and folic acid addition (period 2). The Yobs decreased by 73 and 45% in phases with the OSA-process and folic acid addition, respectively, compared with the control phases. The sludge minimization alternatives result in a decrease in excess sludge production, without negatively affecting the performance of the effluent treatment.

  5. Non-innocent additives in a palladium(II)-catalyzed C-H bond activation reaction: insights into multimetallic active catalysts.

    PubMed

    Anand, Megha; Sunoj, Raghavan B; Schaefer, Henry F

    2014-04-16

    The role of a widely employed additive (AgOAc) in a palladium acetate-catalyzed ortho-C-H bond activation reaction has been examined using the M06 density functional theory. A new hetero-bimetallic Pd-(μ-OAc)3-Ag is identified as the most likely active species. This finding could have far-reaching implications with respect to the notion of the active species in palladium catalysis in the presence of other metal salt additives.

  6. Lewis base activation of Lewis acids: catalytic, enantioselective vinylogous aldol addition reactions.

    PubMed

    Denmark, Scott E; Heemstra, John R

    2007-07-20

    The generality of Lewis base catalyzed, Lewis acid mediated, enantioselective vinylogous aldol addition reactions has been investigated. The combination of silicon tetrachloride and chiral phosphoramides is a competent catalyst for highly selective additions of a variety of alpha,beta-unsaturated ketone-, 1,3-diketone-, and alpha,beta-unsaturated amide-derived dienolates to aldehydes. These reactions provided high levels of gamma-site selectivity for a variety of substitution patterns on the dienyl unit. Both ketone- and morpholine amide-derived dienol ethers afforded high enantio- and diastereoselectivity in the addition to conjugated aldehydes. Although alpha,beta-unsaturated ketone-derived dienolate did not react with aliphatic aldehydes, alpha,beta-unsaturated amide-derived dienolates underwent addition at reasonable rates affording high yields of vinylogous aldol product. The enantioselectivities achieved with the morpholine derived-dienolate in the addition to aliphatic aldehydes was the highest afforded to date with the silicon tetrachloride-chiral phosphoramide system. Furthermore, the ability to cleanly convert the morpholine amide to a methyl ketone was demonstrated.

  7. The LINK-A lncRNA Activates Normoxic HIF1α Signaling in Triple-negative Breast Cancer

    PubMed Central

    Lin, Aifu; Li, Chunlai; Xing, Zhen; Hu, Qingsong; Liang, Ke; Han, Leng; Wang, Cheng; Hawke, David H.; Wang, Shouyu; Zhang, Yanyan; Wei, Yongkun; Ma, Guolin; Park, Peter K.; Zhou, Jianwei; Zhou, Yan; Hu, Zhibin; Zhou, Yubin; Marks, Jeffery R.; Liang, Han; Hung, Mien-Chie; Lin, Chunru; Yang, Liuqing

    2016-01-01

    Although long noncoding RNAs (lncRNAs) predominately reside in nuclear and exert their functions in many biological processes, their potential involvement in cytoplasmic signal transduction remains unexplored. Here, we identified a cytoplasmic lncRNA, Long-Intergenic Noncoding RNA for Kinase Activation (LINK-A), which mediates HB-EGF triggered, EGFR:GPNMB heterodimer-dependent HIF1α phosphorylation at Tyr565 and Ser797 by BRK and LRRK2 respectively. These events cause HIF1α stabilization, HIF1α-p300 interaction, and activation of HIF1α transcriptional programs under normoxic conditions. Mechanistically, LINK-A facilitates the recruitment of BRK to EGFR:GPNMB complex and BRK kinase activation. The BRK-dependent HIF1α Tyr565 phosphorylation interferes with Pro564 hydroxylation, leading to normoxic HIF1α stabilization. Both LINK-A and LINK-A-dependent signaling pathway activation correlate with TNBC, promoting breast cancer glycolysis reprogramming and tumorigenesis. Our findings illustrate the magnitude and diversity of cytoplasmic lncRNAs in signal transduction and highlight the important roles of lncRNAs in cancer. PMID:26751287

  8. FKBP65-dependent peptidyl-prolyl isomerase activity potentiates the lysyl hydroxylase 2-driven collagen cross-link switch

    PubMed Central

    Chen, Yulong; Terajima, Masahiko; Banerjee, Priyam; Guo, Houfu; Liu, Xin; Yu, Jiang; Yamauchi, Mitsuo; Kurie, Jonathan M.

    2017-01-01

    Bruck Syndrome is a connective tissue disease associated with inactivating mutations in lysyl hydroxylase 2 (LH2/PLOD2) or FK506 binding protein 65 (FKBP65/FKBP10). However, the functional relationship between LH2 and FKBP65 remains unclear. Here, we postulated that peptidyl prolyl isomerase (PPIase) activity of FKBP65 positively modulates LH2 enzymatic activity and is critical for the formation of hydroxylysine-aldehyde derived intermolecular collagen cross-links (HLCCs). To test this hypothesis, we analyzed collagen cross-links in Fkbp10-null and –wild-type murine embryonic fibroblasts. Although LH2 protein levels did not change, FKBP65 deficiency significantly diminished HLCCs and increased the non-hydroxylated lysine-aldehyde–derived collagen cross-links (LCCs), a pattern consistent with loss of LH2 enzymatic activity. The HLCC-to-LCC ratio was rescued in FKBP65-deficient murine embryonic fibroblasts by reconstitution with wild-type but not mutant FKBP65 that lacks intact PPIase domains. Findings from co-immunoprecipitation, protein-fragment complementation, and co-immunofluorescence assays showed that LH2 and FKBP65 are part of a common protein complex. We conclude that FKBP65 regulates LH2-mediated collagen cross-linking. Because LH2 promotes fibrosis and cancer metastasis, our findings suggest that pharmacologic strategies to target FKBP65 and LH2 may have complementary therapeutic activities. PMID:28378777

  9. Responses of soil microbial communities and enzyme activities to nitrogen and phosphorus additions in Chinese fir plantations of subtropical China

    NASA Astrophysics Data System (ADS)

    Dong, W. Y.; Zhang, X. Y.; Liu, X. Y.; Fu, X. L.; Chen, F. S.; Wang, H. M.; Sun, X. M.; Wen, X. F.

    2015-07-01

    Nitrogen (N) and phosphorus (P) additions to forest ecosystems are known to influence various above-ground properties, such as plant productivity and composition, and below-ground properties, such as soil nutrient cycling. However, our understanding of how soil microbial communities and their functions respond to nutrient additions in subtropical plantations is still not complete. In this study, we added N and P to Chinese fir plantations in subtropical China to examine how nutrient additions influenced soil microbial community composition and enzyme activities. The results showed that most soil microbial properties were responsive to N and/or P additions, but responses often varied depending on the nutrient added and the quantity added. For instance, there were more than 30 % greater increases in the activities of β-Glucosidase (βG) and N-acetyl-β-D-glucosaminidase (NAG) in the treatments that received nutrient additions compared to the control plot, whereas acid phosphatase (aP) activity was always higher (57 and 71 %, respectively) in the P treatment. N and P additions greatly enhanced the PLFA abundanceespecially in the N2P treatment, the bacterial PLFAs (bacPLFAs), fungal PLFAs (funPLFAs) and actinomycic PLFAs (actPLFAs) were about 2.5, 3 and 4 times higher, respectively, than in the CK. Soil enzyme activities were noticeably higher in November than in July, mainly due to seasonal differences in soil moisture content (SMC). βG or NAG activities were significantly and positively correlated with microbial PLFAs. There were also significant relationships between gram-positive (G+) bacteria and all three soil enzymes. These findings indicate that G+ bacteria is the most important microbial community in C, N, and P transformations in Chinese fir plantations, and that βG and NAG would be useful tools for assessing the biogeochemical transformation and metabolic activity of soil microbes. We recommend combined additions of N and P fertilizer to promote soil

  10. Responses of soil microbial communities and enzyme activities to nitrogen and phosphorus additions in Chinese fir plantations of subtropical China

    NASA Astrophysics Data System (ADS)

    Dong, W. Y.; Zhang, X. Y.; Liu, X. Y.; Fu, X. L.; Chen, F. S.; Wang, H. M.; Sun, X. M.; Wen, X. F.

    2015-09-01

    Nitrogen (N) and phosphorus (P) additions to forest ecosystems are known to influence various above-ground properties, such as plant productivity and composition, and below-ground properties, such as soil nutrient cycling. However, our understanding of how soil microbial communities and their functions respond to nutrient additions in subtropical plantations is still not complete. In this study, we added N and P to Chinese fir plantations in subtropical China to examine how nutrient additions influenced soil microbial community composition and enzyme activities. The results showed that most soil microbial properties were responsive to N and/or P additions, but responses often varied depending on the nutrient added and the quantity added. For instance, there were more than 30 % greater increases in the activities of β-glucosidase (βG) and N-acetyl-β-D-glucosaminidase (NAG) in the treatments that received nutrient additions compared to the control plot, whereas acid phosphatase (aP) activity was always higher (57 and 71 %, respectively) in the P treatment. N and P additions greatly enhanced the phospholipid fatty acids (PLFAs) abundance especially in the N2P (100 kg ha-1 yr-1 of N +50 kg ha-1 yr-1 of P) treatment; the bacterial PLFAs (bacPLFAs), fungal PLFAs (funPLFAs) and actinomycic PLFAs (actPLFAs) were about 2.5, 3 and 4 times higher, respectively, than in the CK (control). Soil enzyme activities were noticeably higher in November than in July, mainly due to seasonal differences in soil moisture content (SMC). βG or NAG activities were significantly and positively correlated with microbial PLFAs. These findings indicate that βG and NAG would be useful tools for assessing the biogeochemical transformation and metabolic activity of soil microbes. We recommend combined additions of N and P fertilizer to promote soil fertility and microbial activity in this kind of plantation.

  11. Linking brain-wide multivoxel activation patterns to behaviour: Examples from language and math.

    PubMed

    Raizada, Rajeev D S; Tsao, Feng-Ming; Liu, Huei-Mei; Holloway, Ian D; Ansari, Daniel; Kuhl, Patricia K

    2010-05-15

    A key goal of cognitive neuroscience is to find simple and direct connections between brain and behaviour. However, fMRI analysis typically involves choices between many possible options, with each choice potentially biasing any brain-behaviour correlations that emerge. Standard methods of fMRI analysis assess each voxel individually, but then face the problem of selection bias when combining those voxels into a region-of-interest, or ROI. Multivariate pattern-based fMRI analysis methods use classifiers to analyse multiple voxels together, but can also introduce selection bias via data-reduction steps as feature selection of voxels, pre-selecting activated regions, or principal components analysis. We show here that strong brain-behaviour links can be revealed without any voxel selection or data reduction, using just plain linear regression as a classifier applied to the whole brain at once, i.e. treating each entire brain volume as a single multi-voxel pattern. The brain-behaviour correlations emerged despite the fact that the classifier was not provided with any information at all about subjects' behaviour, but instead was given only the neural data and its condition-labels. Surprisingly, more powerful classifiers such as a linear SVM and regularised logistic regression produce very similar results. We discuss some possible reasons why the very simple brain-wide linear regression model is able to find correlations with behaviour that are as strong as those obtained on the one hand from a specific ROI and on the other hand from more complex classifiers. In a manner which is unencumbered by arbitrary choices, our approach offers a method for investigating connections between brain and behaviour which is simple, rigorous and direct.

  12. Abrupt aridities in the Levant-Sahel linked with solar activities

    NASA Astrophysics Data System (ADS)

    Stein, M.; Kushnir, Y.

    2012-04-01

    Observations of 19th and 20th century precipitation in the Dead Sea watershed region display a multidecadal, anti-phase relationship to North Atlantic (NAtl) sea surface temperature (SST) variability, such that when the NAtl is relatively cold, Jerusalem experiences higher than normal precipitation and vice versa. This association is underlined by a negative correlation to precipitation in the sub-Saharan Sahel and a positive correlation to precipitation in western North America, areas that are also affected by multidecadal NAtl SST variability. These observations are consistent with broad range of Holocene hydroclimatic fluctuations from the epochal, to the millennial and centennial time scales, as displayed by the Dead Sea and Sahelian lake levels and by direct and indirect proxy indicators of NAtl SSTs. On the epochal time scale, the gradual cooling of NAtl SSTs throughout the Holocene in response to precession-driven reduction of summer insolation is associated with previously well-studied wet-to-dry transition in the Sahel and with a general increase in Dead Sea lake levels from low stands after the Younger Dryas to higher stands in the mid- to late-Holocene. On the millennial and centennial time scales there is also evidence for an antiphase relationship between Holocene variations in the Dead Sea and Sahelian lake levels and with proxy indicators of NAtl SSTs. However, the records are punctuated by abrupt lake-level drops and extensive expansion of the desert belt at ~8.1, 5.7, 3.3 and 1.4 ka cal BP, which appear to be in-phase and which occur during previously documented abrupt major cooling events in the Northern Hemisphere. We link these cooling to solar activity variations that were identified in the North Atlantic IRD and cosmogenic isotopes records.

  13. Preparation, stability and antimicrobial activity of cationic cross-linked starch-iodine complexes.

    PubMed

    Klimaviciute, Rima; Bendoraitiene, Joana; Rutkaite, Ramune; Siugzdaite, Jurate; Zemaitaitis, Algirdas

    2012-12-01

    Cationic cross-linked starch (CCS)-iodine complexes containing different amounts of quaternary ammonium groups (different degrees of substitution (DS)) and iodine have been obtained by iodine adsorption on CCS from aqueous iodine potassium iodide solution. Equilibrium adsorption studies showed that with an increase of DS the amount of iodine adsorbed on CCS and the affinity of iodine to CCS increased linearly. The influences of the DS of CCS and the amount of adsorbed iodine on the stability of CCS-iodine complexes in a solution of 0.02M sodium acetate and reactivity toward l-tyrosine have been investigated. At the same DS, the stability of CCS-iodine complexes decreased with an increase of the amount of adsorbed iodine. With increasing the DS, the stability of CCS-iodine complexes increased. The iodine consumption in the reaction with l-tyrosine increased significantly with an increase of the amount of adsorbed iodine. The influence of DS on iodine consumption was lower and depended on the amount of adsorbed iodine. The antibacterial activity of CCS-iodine complexes against Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli was determined by the broth-dilution and spread-plate methods. The obtained results have demonstrated that an appropriate selection of the CCS-iodine complex composition (the DS of CCS and the amount of adsorbed iodine) could ensure good antimicrobial properties by keeping a low concentration of free iodine in the system. The main advantage of using CCS-iodine complexes as antimicrobial agents is the biodegradability of the polymeric matrix.

  14. Converging genetic and functional brain imaging evidence links neuronal excitability to working memory, psychiatric disease, and brain activity.

    PubMed

    Heck, Angela; Fastenrath, Matthias; Ackermann, Sandra; Auschra, Bianca; Bickel, Horst; Coynel, David; Gschwind, Leo; Jessen, Frank; Kaduszkiewicz, Hanna; Maier, Wolfgang; Milnik, Annette; Pentzek, Michael; Riedel-Heller, Steffi G; Ripke, Stephan; Spalek, Klara; Sullivan, Patrick; Vogler, Christian; Wagner, Michael; Weyerer, Siegfried; Wolfsgruber, Steffen; de Quervain, Dominique J-F; Papassotiropoulos, Andreas

    2014-03-05

    Working memory, the capacity of actively maintaining task-relevant information during a cognitive task, is a heritable trait. Working memory deficits are characteristic for many psychiatric disorders. We performed genome-wide gene set enrichment analyses in multiple independent data sets of young and aged cognitively healthy subjects (n = 2,824) and in a large schizophrenia case-control sample (n = 32,143). The voltage-gated cation channel activity gene set, consisting of genes related to neuronal excitability, was robustly linked to performance in working memory-related tasks across ages and to schizophrenia. Functional brain imaging in 707 healthy participants linked this gene set also to working memory-related activity in the parietal cortex and the cerebellum. Gene set analyses may help to dissect the molecular underpinnings of cognitive dimensions, brain activity, and psychopathology.

  15. 78 FR 52803 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Additional...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-26

    ... OMB under the PRA and displays a currently valid OMB Control Number. In addition, notwithstanding any... collection of information that does not display a valid Control Number. See 5 CFR 1320.5(a) and 1320.6. The DOL obtains OMB approval for this information collection under Control Number 1218-0237....

  16. Studies on the Food Additive Propyl Gallate: Synthesis, Structural Characterization, and Evaluation of the Antioxidant Activity

    ERIC Educational Resources Information Center

    Garrido, Jorge; Garrido, E. Manuela; Borges, Fernanda

    2012-01-01

    Antioxidants are additives largely used in industry for delaying, retarding, or preventing the development of oxidative deterioration. Propyl gallate (E310) is a phenolic antioxidant extensively used in the food, cosmetics, and pharmaceutical industries. A series of lab experiments have been developed to teach students about the importance and…

  17. 42 CFR 424.516 - Additional provider and supplier requirements for enrolling and maintaining active enrollment...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Additional provider and supplier requirements for... on the type of services or supplies the provider or supplier type will furnish and bill Medicare. (3...) Reporting requirements DMEPOS suppliers. DMEPOS reporting requirements are specified in § 424.57(c)(2)....

  18. 42 CFR 424.516 - Additional provider and supplier requirements for enrolling and maintaining active enrollment...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 3 2013-10-01 2013-10-01 false Additional provider and supplier requirements for... on the type of services or supplies the provider or supplier type will furnish and bill Medicare. (3...) Reporting requirements DMEPOS suppliers. DMEPOS reporting requirements are specified in § 424.57(c)(2)....

  19. 42 CFR 424.516 - Additional provider and supplier requirements for enrolling and maintaining active enrollment...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 3 2014-10-01 2014-10-01 false Additional provider and supplier requirements for... on the type of services or supplies the provider or supplier type will furnish and bill Medicare. (3...) Reporting requirements DMEPOS suppliers. DMEPOS reporting requirements are specified in § 424.57(c)(2)....

  20. 42 CFR 424.516 - Additional provider and supplier requirements for enrolling and maintaining active enrollment...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 3 2012-10-01 2012-10-01 false Additional provider and supplier requirements for... on the type of services or supplies the provider or supplier type will furnish and bill Medicare. (3...) Reporting requirements DMEPOS suppliers. DMEPOS reporting requirements are specified in § 424.57(c)(2)....

  1. Effect of powdered activated carbon (PAC) on MBR performance and effluent trihalomethane formation: At the initial stage of PAC addition.

    PubMed

    Gao, Yue; Ma, Defang; Yue, Qinyan; Gao, Baoyu; Huang, Xia

    2016-09-01

    In this study, the MBR was used to treat municipal wastewater for reuse. Effects of powdered activated carbon (PAC) addition on MBR system in terms of effluent water quality, trihalomethane (THM) formation and membrane organic fouling tendency of MBR sludge supernatant at the initial stage of PAC addition were investigated. Effects of chlorine dose and contact time on THM formation and speciation were also studied. PAC addition enhanced the removal of organic matters, especially aromatic components, which improved the UV254 removal rate from 34% to 83%. PAC addition greatly reduced the membrane organic fouling tendency of MBR sludge supernatant. PAC addition reduced the MBR effluent trihalomethane formation potential (THMFP) from 351.29 to 241.95μg/L, while increased THM formation reactivity by 42%. PAC addition enhanced the formation of higher toxic bromine-containing THMs. High chlorine dose and contact time resulted in higher THM formation but lower proportion of bromine-containing THMs.

  2. Linking Prenatal Androgens to Gender-Related Attitudes, Identity, and Activities: Evidence From Girls With Congenital Adrenal Hyperplasia.

    PubMed

    Endendijk, Joyce J; Beltz, Adriene M; McHale, Susan M; Bryk, Kristina; Berenbaum, Sheri A

    2016-10-01

    Key questions for developmentalists concern the origins of gender attitudes and their implications for behavior. We examined whether prenatal androgen exposure was related to gender attitudes, and whether and how the links between attitudes and gendered activity interest and participation were mediated by gender identity and moderated by hormones. Gender attitudes (i.e., gender-role attitudes and attitudes about being a girl), gender identity, and gender-typed activities were reported by 54 girls aged 10-13 years varying in degree of prenatal androgen exposure, including 40 girls with classical congenital adrenal hyperplasia (C-CAH) exposed to high prenatal androgens and 14 girls with non-classical (NC) CAH exposed to low, female-typical, prenatal androgens. Both girls with C-CAH and NC-CAH reported positive attitudes about being a girl and egalitarian gender attitudes, consistent with their female-typical gender identity. In contrast, girls with C-CAH had more male-typed activity interest and participation than girls with NC-CAH. Gender attitudes were linked to activities in both groups, with gender identity mediating the links. Specifically, gender-role attitudes and positive attitudes about being a girl were associated with feminine gender identity, which in turn was associated with decreased male-typed activity interests and participation, and increased female-typed activity interests. Our results are consistent with schema theories, with attitudes more closely associated with gender identity than with prenatal androgens.

  3. Insulin analog with additional disulfide bond has increased stability and preserved activity

    PubMed Central

    Vinther, Tine N; Norrman, Mathias; Ribel, Ulla; Huus, Kasper; Schlein, Morten; Steensgaard, Dorte B; Pedersen, Thomas Å; Pettersson, Ingrid; Ludvigsen, Svend; Kjeldsen, Thomas; Jensen, Knud J; Hubálek, František

    2013-01-01

    Insulin is a key hormone controlling glucose homeostasis. All known vertebrate insulin analogs have a classical structure with three 100% conserved disulfide bonds that are essential for structural stability and thus the function of insulin. It might be hypothesized that an additional disulfide bond may enhance insulin structural stability which would be highly desirable in a pharmaceutical use. To address this hypothesis, we designed insulin with an additional interchain disulfide bond in positions A10/B4 based on Cα-Cα distances, solvent exposure, and side-chain orientation in human insulin (HI) structure. This insulin analog had increased affinity for the insulin receptor and apparently augmented glucodynamic potency in a normal rat model compared with HI. Addition of the disulfide bond also resulted in a 34.6°C increase in melting temperature and prevented insulin fibril formation under high physical stress even though the C-terminus of the B-chain thought to be directly involved in fibril formation was not modified. Importantly, this analog was capable of forming hexamer upon Zn addition as typical for wild-type insulin and its crystal structure showed only minor deviations from the classical insulin structure. Furthermore, the additional disulfide bond prevented this insulin analog from adopting the R-state conformation and thus showing that the R-state conformation is not a prerequisite for binding to insulin receptor as previously suggested. In summary, this is the first example of an insulin analog featuring a fourth disulfide bond with increased structural stability and retained function. PMID:23281053

  4. Impact of lubricant additives on the physicochemical properties and activity of three-way catalysts

    SciTech Connect

    Toops, Todd J.; Lance, Michael J.; Qu, Jun; Viola, Michael B; Lewis, Samuel Arthur; Leonard, Donovan N.; Edward W. Hagaman; Xie, Chao

    2016-04-04

    As alternative lubricant anti-wear additives are sought to reduce friction and improve overall fuel economy, it is important that these additives are also compatible with current emissions control catalysts. In the present work, an oil-miscible phosphorous-containing ionic liquid (IL), trihexyltetradecylphosphonium bis(2-ethylhexyl) phosphate ([P66614][DEHP]), is evaluated for its impact on three-way catalysts (TWC) and benchmarked against the industry standard zinc-dialkyl-dithio-phosphate (ZDDP). The TWCs are aged in different scenarios: neat gasoline (no-additive, or NA), gasoline+ZDDP, and gasoline+IL. The aged samples, along with the as received TWC, are characterized through various analytical techniques including catalyst reactivity evaluation in a bench-flow reactor. The temperatures of 50% conversion (T50) for the ZDDP-aged TWCs increased by 30, 24, and 25 °C for NO, CO, and C3H6, respectively, compared to the no-additive case. Although the IL-aged TWC also increased in T50 for CO and C3H6, it was notably less than ZDDP, 7 and 9 °C, respectively. Additionally, the IL-aged samples had higher water-gas-shift reactivity and oxygen storage capacity than the ZDDP-aged TWC. Characterization of the aged samples indicated the predominant presence of CePO4 in the ZDDP-aged TWC aged by ZDDP, while its formation was retarded in the case of IL where higher levels of AlPO4 is observed. Furthermore, the results in this work indicate that the phosphonium-phosphate IL potentially has less adverse impact on TWC than ZDDP.

  5. Impact of lubricant additives on the physicochemical properties and activity of three-way catalysts

    DOE PAGES

    Toops, Todd J.; Lance, Michael J.; Qu, Jun; ...

    2016-04-04

    As alternative lubricant anti-wear additives are sought to reduce friction and improve overall fuel economy, it is important that these additives are also compatible with current emissions control catalysts. In the present work, an oil-miscible phosphorous-containing ionic liquid (IL), trihexyltetradecylphosphonium bis(2-ethylhexyl) phosphate ([P66614][DEHP]), is evaluated for its impact on three-way catalysts (TWC) and benchmarked against the industry standard zinc-dialkyl-dithio-phosphate (ZDDP). The TWCs are aged in different scenarios: neat gasoline (no-additive, or NA), gasoline+ZDDP, and gasoline+IL. The aged samples, along with the as received TWC, are characterized through various analytical techniques including catalyst reactivity evaluation in a bench-flow reactor. The temperaturesmore » of 50% conversion (T50) for the ZDDP-aged TWCs increased by 30, 24, and 25 °C for NO, CO, and C3H6, respectively, compared to the no-additive case. Although the IL-aged TWC also increased in T50 for CO and C3H6, it was notably less than ZDDP, 7 and 9 °C, respectively. Additionally, the IL-aged samples had higher water-gas-shift reactivity and oxygen storage capacity than the ZDDP-aged TWC. Characterization of the aged samples indicated the predominant presence of CePO4 in the ZDDP-aged TWC aged by ZDDP, while its formation was retarded in the case of IL where higher levels of AlPO4 is observed. Furthermore, the results in this work indicate that the phosphonium-phosphate IL potentially has less adverse impact on TWC than ZDDP.« less

  6. Activation and stabilization of the hydroperoxide lyase enzymatic extract from mint leaves (Mentha spicata) using selected chemical additives.

    PubMed

    Akacha, Najla B; Karboune, Salwa; Gargouri, Mohamed; Kermasha, Selim

    2010-03-01

    The effects of selected lyoprotecting excipients and chemical additives on the specific activity and the thermal stability of the hydroperoxide lyase (HPL) enzymatic extract from mint leaves were investigated. The addition of KCl (5%, w/w) and dextran (2.5%, w/w) to the enzymatic extract, prior to lyophilization, increased the HPL specific activity by 2.0- and 1.2-fold, respectively, compared to the control lyophilized extract. From half-life time (t (1/2)), it can be seen that KCl has enhanced the HPL stability by 1.3- to 2.3-fold, during long-period storage at -20 degrees Celsius and 4 degrees Celsius. Among the selected additives used throughout this study, glycine appeared to be the most effective one. In addition to the activation effect conferred by glycine, it also enhanced the HPL thermal stability. In contrast, polyhydroxyl-containing additives were not effective for stabilizing the HPL enzymatic extract. On the other hand, there was no signification increase in HPL activity and its thermal stability with the presence of Triton X-100. The results also showed that in the presence of glycine (10%), the catalytic efficiency of HPL was increased by 2.45-fold than that without additive.

  7. Physical Activity Is Linked to Greater Moment-To-Moment Variability in Spontaneous Brain Activity in Older Adults

    PubMed Central

    Burzynska, Agnieszka Z.; Wong, Chelsea N.; Voss, Michelle W.; Cooke, Gillian E.; Gothe, Neha P.; Fanning, Jason; McAuley, Edward; Kramer, Arthur F.

    2015-01-01

    Higher cardiorespiratory fitness (CRF) and physical activity (PA) in old age are associated with greater brain structural and functional integrity, and higher cognitive functioning. However, it is not known how different aspects of lifestyle such as sedentariness, light PA (LI-PA), or moderate-to-vigorous physical activity (MV-PA) relate to neural activity in aging. In addition, it is not known whether the effects of PA on brain function differ or overlap with those of CRF. Here, we objectively measured CRF as oxygen consumption during a maximal exercise test and measured PA with an accelerometer worn for 7 days in 100 healthy but low active older adults (aged 60–80 years). We modeled the relationships between CRF, PA, and brain functional integrity using multivariate partial least squares analysis. As an index of functional brain integrity we used spontaneous moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD), known to be associated with better cognitive functioning in aging. We found that older adults who engaged more in LI-PA and MV-PA had greater SDBOLD in brain regions that play a role in integrating segregated functional domains in the brain and benefit from greater CRF or PA, such as precuneus, hippocampus, medial and lateral prefrontal, and temporal cortices. Our results suggest that engaging in higher intensity PA may have protective effects on neural processing in aging. Finally, we demonstrated that older adults with greater overall WM microstructure were those showing more LI-PA and MV-PA and greater SDBOLD. We conclude that SDBOLD is a promising correlate of functional brain health in aging. Future analyses will evaluate whether SDBOLD is modifiable with interventions aimed to increase PA and CRF in older adults. PMID:26244873

  8. Analysis of space environment effects on active fiber optic links orbited aboard the LDEF. [long duration exposure facility

    NASA Technical Reports Server (NTRS)

    Monarski, T. W.; Berry, J. N.; Sanchez, A. D.; Padden, R. J.; Chapman, S. P.; Taylor, E. W.

    1992-01-01

    The interim analysis correlates the results of the 'Preliminary Analysis of WL Experiment no. 701, Space Environment Effects on Operating Optic Systems' (NASA Report CP-3134) with space simulated post retrieval terrestrial studies performed on the M0004 experiment. Temperature cycling measurements were performed on the active optical data links for the purpose of assessing link signal to noise ratio and bit error rate performance some 69 months following the experiment deployment in low earth orbit. The early results indicate a high correlation between pre-orbit, orbit recorded, and post orbit functionality of the first known and longest space demonstration of operating optic fibers.

  9. Linking Changes to Intraspecific Trait Diversity to Community Functional Diversity and Biomass in Response to Snow and Nitrogen Addition Within an Inner Mongolian Grassland

    PubMed Central

    Mao, Wei; Felton, Andrew J.; Zhang, Tonghui

    2017-01-01

    In recent years, both the intraspecific and interspecific functional diversity (FD) of plant communities have been studied with new approaches to improve an understanding about the mechanisms underlying plant species coexistence. Yet, little is known about how global change drivers will impact intraspecific FD and trait overlap among species, and in particular how this may scale to impacts on community level FD and ecosystem functioning. To address this uncertainty, we assessed the direct and indirect responses of specific leaf area (SLA) among both dominant annual and subordinate perennial species to the independent and interactive effects of nitrogen and snow addition within the Inner Mongnolian steppe. More specifically, we investigated the consequences for these responses on plant community FD, trait overlap and biomass. Nitrogen addition increased the biomass of the dominant annual species and as a result increased total community biomass. This occurred despite concurrent decreases in the biomass of subordinate perennial species. Nitrogen addition also increased intraspecific FD and trait overlap of both annual species and perennial species, and consequently increased the degree of trait overlap in SLA at the community level. However, snow addition did not significantly impact intraspecific FD and trait overlap of SLA for perennial species, but increased intraspecific FD and trait overlap of annual species, of which scaled to changes in community level FD. We found that the responses of the dominant annual species to nitrogen and snow additions were generally more sensitive than the subordinate perennial species within the inner Mongolian grassland communities of our study. As a consequence of this sensitivity, the responses of the dominant species largely drove impacts to community FD, trait overlap and community biomass. In total, our study demonstrates that the responses of dominant species in a community to environmental change may drive the initial

  10. Estrogen modification of human glutamate dehydrogenases is linked to enzyme activation state.

    PubMed

    Borompokas, Nikolas; Papachatzaki, Maria-Martha; Kanavouras, Konstantinos; Mastorodemos, Vasileios; Zaganas, Ioannis; Spanaki, Cleanthe; Plaitakis, Andreas

    2010-10-08

    Mammalian glutamate dehydrogenase (GDH) is a housekeeping enzyme central to the metabolism of glutamate. Its activity is potently inhibited by GTP (IC(50) = 0.1-0.3 μM) and thought to be controlled by the need of the cell in ATP. Estrogens are also known to inhibit mammalian GDH, but at relatively high concentrations. Because, in addition to this housekeeping human (h) GDH1, humans have acquired via a duplication event an hGDH2 isoform expressed in human cortical astrocytes, we tested here the interaction of estrogens with the two human isoenzymes. The results showed that, under base-line conditions, diethylstilbestrol potently inhibited hGDH2 (IC(50) = 0.08 ± 0.01 μM) and with ∼18-fold lower affinity hGDH1 (IC(50) = 1.67 ± 0.06 μM; p < 0.001). Similarly, 17β-estradiol showed a ∼18-fold higher affinity for hGDH2 (IC(50) = 1.53 ± 0.24 μM) than for hGDH1 (IC(50) = 26.94 ± 1.07 μM; p < 0.001). Also, estriol and progesterone were more potent inhibitors of hGDH2 than hGDH1. Structure/function analyses revealed that the evolutionary R443S substitution, which confers low basal activity, was largely responsible for sensitivity of hGDH2 to estrogens. Inhibition of both human GDHs by estrogens was inversely related to their state of activation induced by ADP, with the slope of this correlation being steeper for hGDH2 than for hGDH1. Also, the study of hGDH1 and hGDH2 mutants displaying different states of activation revealed that the affinity of estrogen for these enzymes correlated inversely (R = 0.99; p = 0.0001) with basal catalytic activity. Because astrocytes are known to synthesize estrogens, these hormones, by interacting potently with hGDH2 in its closed state, may contribute to regulation of glutamate metabolism in brain.

  11. Early-Late Heterobimetallic Complexes Linked by Phosphinoamide Ligands. Tuning Redox Potentials and Small Molecule Activation

    SciTech Connect

    Thomas, Christine M.

    2015-08-01

    Recent attention in the chemical community has been focused on the energy efficient and environmentally benign conversion of abundant small molecules (CO2, H2O, etc.) to useful liquid fuels. This project addresses these goals by examining fundamental aspects of catalyst design to ultimately access small molecule activation processes under mild conditions. Specifically, Thomas and coworkers have targetted heterobimetallic complexes that feature metal centers with vastly different electronic properties, dictated both by their respective positions on the periodic table and their coordination environment. Unlike homobimetallic complexes featuring identical or similar metals, the bonds between metals in early/late heterobimetallics are more polarized, with the more electron-rich late metal center donating electron density to the more electron-deficient early metal center. While metal-metal bonds pose an interesting strategy for storing redox equivalents and stabilizing reactive metal fragments, the polar character of metal-metal bonds in heterobimetallic complexes renders these molecules ideally poised to react with small molecule substrates via cleavage of energy-rich single and double bonds. In addition, metal-metal interactions have been shown to dramatically affect redox potentials and promote multielectron redox activity, suggesting that metal-metal interactions may provide a mechanism to tune redox potentials and access substrate reduction/activation at mild overpotentials. This research project has provided a better fundamental understanding of how interactions between transition metals can be used as a strategy to promote and/or control chemical transformations related to the clean production of fuels. While this project focused on the study of homogeneous systems, it is anticipated that the broad conclusions drawn from these investigations will be applicable to heterogeneous catalysis as well, particularly on heterogeneous processes that occur at interfaces in

  12. Aggregation of Cricket Activity in Response to Resource Addition Increases Local Diversity.

    PubMed

    Szinwelski, Neucir; Rosa, Cassiano Sousa; Solar, Ricardo Ribeiro de Castro; Sperber, Carlos Frankl

    2015-01-01

    Crickets are often found feeding on fallen fruits among forest litter. Fruits and other sugar-rich resources are not homogeneously distributed, nor are they always available. We therefore expect that crickets dwelling in forest litter have a limited supply of sugar-rich resource, and will perceive this and displace towards resource-supplemented sites. Here we evaluate how sugar availability affects cricket species richness and abundance in old-growth Atlantic forest by spraying sugarcane syrup on leaf litter, simulating increasing availability, and collecting crickets via pitfall trapping. We found an asymptotic positive association between resource addition and species richness, and an interaction between resource addition and species identity on cricket abundance, which indicates differential effects of resource addition among cricket species. Our results indicate that 12 of the 13 cricket species present in forest litter are maintained at low densities by resource scarcity; this highlights sugar-rich resource as a short-term driver of litter cricket community structure in tropical forests. When resource was experimentally increased, species richness increased due to behavioral displacement. We present evidence that the density of many species is limited by resource scarcity and, when resources are added, behavioral displacement promotes increased species packing and alters species composition. Further, our findings have technical applicability for increasing sampling efficiency of local cricket diversity in studies aiming to estimate species richness, but with no regard to local environmental drivers or species-abundance characteristics.

  13. Evidence for Dose-Additive Effects of Pyrethroids on Motor Activity in Rats

    EPA Science Inventory

    BACKGROUND: Pyrethroids are neurotoxic insecticides used in a variety of indoor and outdoor applications. Previous research characterized the acute dose-effect functions for 11 pyrethroids administered orally in corn oil (1 mL/kg) based on assessment of motor activity. OBJECTIVES...

  14. Two step novel hydrogen system using additives to enhance hydrogen release from the hydrolysis of alane and activated aluminum

    SciTech Connect

    Zidan, Ragaiy; Teprovich, Joseph A.; Motyka, Theodore

    2015-12-01

    A system for the generation of hydrogen for use in portable power systems is set forth utilizing a two-step process that involves the thermal decomposition of AlH.sub.3 (10 wt % H.sub.2) followed by the hydrolysis of the activated aluminum (Al*) byproduct to release additional H.sub.2. Additionally, a process in which water is added directly without prior history to the AlH.sub.3:PA composite is also disclosed.

  15. Para-aminobenzamidine linked regenerated cellulose membranes for plasminogen activator purification: effect of spacer arm length and ligand density.

    PubMed

    Fasoli, Ezio; Reyes, Yiaslin Ruiz; Guzman, Osiris Martinez; Rosado, Alexandra; Cruz, Vivian Rodriguez; Borges, Amaris; Martinez, Edmarie; Bansal, Vibha

    2013-07-01

    Despite membrane-based separations offering superior alternative to packed bed chromatographic processes, there has been a substantial lacuna in their actual application to separation processes. One of the major reasons behind this is the lack of availability of appropriately modified or end-group modifiable membranes. In this paper, an affinity membrane was developed using a commercially available serine protease inhibitor, para-aminobenzamidine (pABA). The membrane modification was optimized for protein binding capacity by varying: (i) the length of the spacer arm (SA; 5-atoms, 7-atoms, and 14-atoms) linking the ligand to membrane surface; (ii) the affinity ligand (pABA) density on membrane surface (5-25nmol/cm(2)). Resulting membranes were tested for their ability to bind plasminogen activators (PAs) from mono- and multi-component systems in batch mode. The membrane containing pABA linked through 7-atoms SA but similar ligand density as in the case of 5- or 14-atoms long SA was found to bind up to 1.6-times higher amounts of PA per nmoles of immobilized ligand from conditioned HeLa cell culture media. However, membranes with similar ligand densities but different lengths of SA, showed comparable binding capacities in mono-component system. In addition, the length of SA did not affect the selectivity of the ligand for PA. A clear inverse linear correlation was observed between ligand density and binding capacity until the point of PA binding optima was reached (11±1.0nmol/cm(2)) in mono- and multi-component systems for 7- as well as 14-atoms SA. Up to 200-fold purification was achieved in a single step separation of PA from HeLa conditioned media using these affinity membranes. The issues of ligand leaching and reuse of the membranes were also investigated. An extensive regeneration procedure allowed the preservation of approximately 95% of the PA binding capacity of the membranes even after five cycles of use.

  16. Improvement of the fermentative activity of lactic acid bacteria starter culture by the addition of Mn²⁺.

    PubMed

    Cheng, Xin; Dong, Ying; Su, Ping; Xiao, Xiang

    2014-11-01

    Production of lactic acid bacteria (LAB) starter with raw material has received much scientific investigation, but little information is available on the influences of some trace elements on the growth and fermentative activity of LAB. Based on this fact, this paper aimed to investigate the effects of Mn(2+) on the performance of Lactobacillus plantarum CX-15 starter with Jerusalem artichoke (JA) as the main medium substrate. The results showed that Mn(2+) addition had a significant beneficial affect on the fermentative activity of L. plantarum CX-15 starter. In contrast, the lack of Mn(2+) would cause the subsequent fermentation significantly slower, whether the cell density in starter culture was higher or lower. The possible mechanism of these phenomenons was further elucidated by the time course analysis of the specific activities of metabolism key enzymes during the culture processes of L. plantarum CX-15 starter. Compared to the fermentation processes without Mn(2+) addition, it was found that Mn(2+) addition would enhance the lactate dehydrogenase (LDH) activity but reduce the activities of pyruvate dehydrogenase (PDH) and ATPase activity. Therefore, it could be concluded that the improvement of L. plantarum starter fermentative activity was probably a consequence of Mn(2+) acting as "metabolic switch," which regulated the metabolic flux from pyruvic acid to lactic acid and other metabolism pathway.

  17. Additive Manufacturing (AM) Activities and Non-Destructive Evaluation (NDE) at GSFC

    NASA Technical Reports Server (NTRS)

    Jones, Justin S.

    2017-01-01

    NASA personnel will be meeting with a delegation from the Japan Aerospace Exploration Agency (JAXA) Office of Safety and Mission Assurance (OSMA) at Langley Research Center on 2217 through 3217. The purpose of the meeting is a technical interchange between NASA and JAXA to discuss Non-Destructive Evaluation (NDE) of Additive Manufacturing (AM) parts and the HALT process (relates to accelerated life testing). The visitors will be a small group of Japanese citizens. Goddard Space Flight Center (GSFC) has been asked to participate in the meeting, either in person or via teleconference. This presentation covers NDE efforts at GSFC and provides a cursory overview of AM and lab capabilities.

  18. Additive-free controllable fabrication of bismuth vanadates and their photocatalytic activity toward dye degradation

    NASA Astrophysics Data System (ADS)

    Guo, Yingna; Yang, Xia; Ma, Fengyan; Li, Kexin; Xu, Lei; Yuan, Xing; Guo, Yihang

    2010-01-01

    Bismuth vanadates (BiVO 4) with various crystal structures (tetragonal scheelite, monoclinic scheelite, and tetragonal zircon) and morphologies (sphere-, nanosheet-, dendrite-, and flower-like) were controllably fabricated by using a mild additive-free hydrothermal treatment process under the different preparation conditions. The crystal structures, morphologies, and photophysical properties of the products were well-characterized. Subsequently, their UV- as well as visible-light photocatalytic performance was evaluated via dyes rhodamine B (RB) and methylene blue (MB) degradation. Special attention was paid to evaluate the correlation of the reactivity with crystal structure, morphology, and electronic structure of as-prepared BiVO 4 samples.

  19. Additional antitumor ecteinascidins from a Caribbean tunicate: crystal structures and activities in vivo.

    PubMed Central

    Sakai, R; Rinehart, K L; Guan, Y; Wang, A H

    1992-01-01

    Ecteinascidins (Ets), isolated from the Caribbean tunicate Ecteinascidia turbinata, protect mice in vivo against P388 lymphoma, B16 melanoma, M5076 ovarian sarcoma, Lewis lung carcinoma, and the LX-1 human lung and MX-1 human mammary carcinoma xenografts. Crystal structures of two tris(tetrahydroisoquinoline) Ets were investigated with single crystals of the 21-O-methyl-N12-formyl derivative of Et 729 and the natural N12-oxide of Et 743. Representatives of an additional class of Ets, Et 722 and Et 736, isolated from the same organism, were assigned tetrahydro-beta-carboline-substituted bis(tetrahydroisoquinoline) structures by NMR and fast atom bombardment MS spectra. PMID:1454834

  20. Suppression of flow pulsation activity by relaxation process of additive effect on viscous media transport

    NASA Astrophysics Data System (ADS)

    Kharlamov, S.; Dedeyev, P.; Meucci, L.; Shenderova, I.; Manastirniy, A.; Usenko, M.

    2015-11-01

    The article presents the analysis of the processes occurring together with the turbulent transfer of impulse in mixture of hydrocarbon fluid and polymer solutions (anti-turbulent additives). The study evaluates complex shear flows by popular theoretical and practical methods. Understanding of hydrodynamic and dissipative effects of laminar-turbulent transition tightening and turbulence suppression is provided. The peculiarities of "thin" flow structure in pipeline zones with complex shape walls are evaluated. Recommendations to forecast the local flow parameters, calculation of hydraulic resistance are given.

  1. Nucleophilic Dearomatization of Pyridines under Enamine Catalysis: Regio-, Diastereo-, and Enantioselective Addition of Aldehydes to Activated N-Alkylpyridinium Salts.

    PubMed

    Bertuzzi, Giulio; Sinisi, Alessandro; Pecorari, Daniel; Caruana, Lorenzo; Mazzanti, Andrea; Bernardi, Luca; Fochi, Mariafrancesca

    2017-02-17

    Catalytic addition of chiral enamines to azinium salts is a powerful tool for the synthesis of enantioenriched heterocycles. An unprecedented asymmetric dearomative addition of aldehydes to activated N-alkylpyridinium salts is presented. The process exhibits complete C-4 regioselectivity along with high levels of diastereo- and enantiocontrol, achieving a high-yielding synthesis of a broad range of optically active 1,4-dihydropyridines. Moreover, the presented methodology enables the synthesis of functionalized octahydropyrrolo[2,3-c]pyridines, the core structure of anticancer peptidomimetics.

  2. Nitroxide polymer networks formed by Michael addition: on site-cured electrode-active organic coating.

    PubMed

    Ibe, Takeshi; Frings, Rainer B; Lachowicz, Artur; Kyo, Soichi; Nishide, Hiroyuki

    2010-05-28

    Highly and homogeneously crosslinked poly(beta-ketoester) networks densely bearing robust nitroxide radicals were prepared via a click-type and stepwise Michael polyaddition. A half-battery cell composed of the thermally-cured radical network coatings displayed a rapid, reversible, and almost stoichiometric redox-activity even with a thickness of ca. 10 mum, which may be applicable as the electrode of organic-based rechargeable devices.

  3. The influence of vibration type, frequency, body position and additional load on the neuromuscular activity during whole body vibration.

    PubMed

    Ritzmann, Ramona; Gollhofer, Albert; Kramer, Andreas

    2013-01-01

    This study aimed to assess the influence of different whole body vibration (WBV) determinants on the electromyographic (EMG) activity during WBV in order to identify those training conditions that cause highest neuromuscular responses and therefore provide optimal training conditions. In a randomized cross-over study, the EMG activity of six leg muscles was analyzed in 18 subjects with respect to the following determinants: (1) vibration type (side-alternating vibration (SV) vs. synchronous vibration (SyV), (2) frequency (5-10-15-20-25-30 Hz), (3) knee flexion angle (10°-30°-60°), (4) stance condition (forefoot vs. normal stance) and (5) load variation (no extra load vs. additional load equal to one-third of the body weight). The results are: (1) neuromuscular activity during SV was enhanced compared to SyV (P < 0.05); (2) a progressive increase in frequency caused a progressive increase in EMG activity (P < 0.05); (3) the EMG activity was highest for the knee extensors when the knee joint was 60° flexed (P < 0.05); (4) for the plantar flexors in the forefoot stance condition (P < 0.05); and (5) additional load caused an increase in neuromuscular activation (P < 0.05). In conclusion, large variations of the EMG activation could be observed across conditions. However, with an appropriate adjustment of specific WBV determinants, high EMG activations and therefore high activation intensities could be achieved in the selected muscles. The combination of high vibration frequencies with additional load on an SV platform led to highest EMG activities. Regarding the body position, a knee flexion of 60° and forefoot stance appear to be beneficial for the knee extensors and the plantar flexors, respectively.

  4. The First Example of Nickel-Catalyzed Silyl-Heck Reactions: Direct Activation of Silyl Triflates Without Iodide Additives

    PubMed Central

    McAtee, Jesse R.; Martin, Sara E. S.; Cinderella, Andrew P.; Reid, William B.; Johnson, Keywan A.

    2014-01-01

    For the first time, nickel-catalyzed silyl-Heck reactions are reported. Using simple phosphine-supported nickel catalysts, direct activation of silyl triflates has been achieved. These results contrast earlier palladium-catalyzed systems, which require iodide additives to activate silyl-triflates. These nickel-based catalysts exhibit good functional group tolerance in the preparation of vinyl silanes, and unlike earlier systems, allows for the incorporation of trialkylsilanes larger than Me3Si. PMID:24914247

  5. Linking observations at active volcanoes to physical processes through conduit flow modelling

    NASA Astrophysics Data System (ADS)

    Thomas, Mark; Neuberg, Jurgen

    2010-05-01

    of the Low frequency events observed on Montserrat is their tightly confined source region. The high degree of similarity of the waveforms from such events indicates a stationary common source within a finite volume of 150m x 150m x 150m (Neuberg et al., 2006). By modelling the physical processes that occur at depth within the volcano it has been possible to identify a potential source region of these events caused by the shape of the conduit, that has a fixed position and will have the potential cause repeatable events whenever magma is moving within the system. Making links of this type is essential to form a better understanding of what the observations made by monitoring systems actually relate to in terms of the volcanoes activity. Tuffen, H., Dingwell, D.B., and Pinkerton, H. 2003. Repeated fracture and healing of silicic magma generate flow banding and earthquakes? Geology, 31(12), 1089-1092. Collier, L. and Neuberg, J. 2006. Incorporating seismic observations into 2D conduit flow modelling. Journal of volcanology and geothermal research, 152, 331-346. Neuberg, J., Tuffen, H., Collier, L., Green, D., Powell, T., and Dingwell, P. 2006. The trigger mechanisms of low-frequency swarms on Montserrat. Journal of volcanology and geothermal research, 153, 37-50.

  6. Additive manufactured polymeric 3D scaffolds with tailored surface topography influence mesenchymal stromal cells activity.

    PubMed

    Neves, Sara C; Mota, Carlos; Longoni, Alessia; Barrias, Cristina C; Granja, Pedro L; Moroni, Lorenzo

    2016-05-24

    Additive manufactured three-dimensional (3D) scaffolds with tailored surface topography constitute a clear advantage in tissue regeneration strategies to steer cell behavior. 3D fibrous scaffolds of poly(ethylene oxide terephthalate)/poly(butylene terephthalate) block copolymer presenting different fiber surface features were successfully fabricated by additive manufacturing combined with wet-spinning, in a single step, without any post-processing. The optimization of the processing parameters, mainly driven by different solvent/non-solvent combinations, led to four distinct scaffold types, with average surface roughness values ranging from 0.071 ± 0.012 μm to 1.950 ± 0.553 μm, average pore sizes in the x- and y-axis between 351.1 ± 33.6 μm and 396.1 ± 32.3 μm, in the z-axis between 36.5 ± 5.3 μm and 70.7 ± 8.8 μm, average fiber diameters between 69.4 ± 6.1 μm and 99.0 ± 9.4 μm, and porosity values ranging from 60.2 ± 0.8% to 71.7 ± 2.6%. Human mesenchymal stromal cells (hMSCs) cultured on these scaffolds adhered, proliferated, and produced endogenous extracellular matrix. The effect of surface roughness and topography on hMSCs differentiation was more evident for cells seeded at lower density, where the percentage of cells in direct contact with the surface was higher compared to more densely seeded scaffolds. Under osteogenic conditions, lower surface roughness values (0.227 ± 0.035 μm) had a synergistic effect on hMSCs behavior, while chondrogenesis was favored on rougher surfaces (1.950 ± 0.553 μm).

  7. Review and Analysis of the Role, Activities, and Training of Educational Linking Agents. Final Report.

    ERIC Educational Resources Information Center

    Piele, Philip K.

    A linking agent is a person or team operating at the interface between resources and the school systems for the purpose of facilitating change by producing interaction between the two, thereby reducing the difference between potential and actual educational practice. This discussion of agent roles and training proceeds from a discussion of change…

  8. Reduction of Aggressive Behaviors with Changes in Activity: Linking Descriptive and Experimental Analyses.

    ERIC Educational Resources Information Center

    Hall, Arlene; Neuharth-Prichett, Stacey; Belfiore, Phillip J.

    1997-01-01

    A study utilized both Descriptive Analysis (DA) and Experimental Analysis (EA) to examine the function of aggressive and destructive behavior for a boy (age 9) with Down syndrome and moderate mental retardation. By linking the two methods, an intervention was designed that decreased the student's aggressive/destructive behavior. (Author/CR)

  9. Clostridium difficile flagella predominantly activate TLR5-linked NF-κB pathway in epithelial cells.

    PubMed

    Batah, Jameel; Denève-Larrazet, Cécile; Jolivot, Pierre-Alain; Kuehne, Sarah; Collignon, Anne; Marvaud, Jean-Christophe; Kansau, Imad

    2016-04-01

    Clostridium difficile has become the most common enteropathogen responsible for intestinal nosocomial post-antibiotic infections. This has coincided with the appearance of serious cases related to the emergence of hypervirulent strains. The toxins are the main virulence factors and elicit an inflammatory response during C. difficile infection. However, other bacterial components appear to be involved in the inflammatory process. In some pathogens, flagella play a role in pathogenesis through abnormal stimulation of the TLR5-mediated host immune response. To date, few studies have addressed this role for C. difficile flagella. In the current study, we confirm in two different epithelial cell models that C. difficile thanks to its FliC flagellin interacts with TLR5. In addition, thanks to inhibition and transcriptomic studies we demonstrate that the interaction of flagellin and TLR5 predominantly activates the NF-κB and, in a lesser degree, the MAPK pathways, via TLR5, leading to up-regulation of pro-inflammatory gene expression and synthesis of pro-inflammatory mediators. These results suggest a role for C. difficile flagella in contributing to inflammatory response in host intestinal cells.

  10. Additive antimicrobial [corrected] effects of the active components of the essential oil of Thymus vulgaris--chemotype carvacrol.

    PubMed

    Iten, Felix; Saller, Reinhard; Abel, Gudrun; Reichling, Jürgen

    2009-09-01

    Herbal remedies are multicomponent mixtures by their nature as well as by pharmaceutical definition. Being a multicomponent mixture is not only a crucial property of herbal remedies, it also represents a precondition for interactions such as synergism or antagonism. Until now, only a few phytomedicines are accurately described concerning the interactions of their active components. The aim of this study was to search for interactions within such a naturally given multi-component mixture and to discuss the pharmaceutical and clinical impacts. The thyme oil chosen for the examination belongs to the essential oils with the most pronounced antimicrobial activity. Antibiotic activity of thyme oil and single active components were tested against six different strains of microorganisms. The checkerboard assay was used to search for interactions. The time-kill assay was used to verify the observed effects and to get information about the temporal resolution of the antimicrobial activity. The degree of the detected interactions corresponded with the demarcating FICI measure of 0.5, which separates the additive from the over-additive (synergistic) effects. Therefore, the observed effect was called a "borderline case of synergism" or, respectively, "partial synergism". Partial synergism was observed only in the presence of Klebsiella pneumoniae. Additive antimicrobial activity was observed for the combination of the two monosubstances carvacrol plus linalool and thymol plus linalool as well as with the combination of the two essential oils of the carvacrol and linalool chemotypes. An increase of the carvacrol oil concentration from one to two times the MIC resulted in a considerable acceleration of the kill-rate. Thyme oil is composed of several different components that show antimicrobial activity (at least: carvacrol, thymol and linalool). The antimicrobial activity of thyme oil is partly based on additive effects, which might especially enhance the rapidity of the

  11. Comparison of symptoms and treatment outcomes between actively and passively detected tuberculosis cases: the additional value of active case finding.

    PubMed

    den Boon, S; Verver, S; Lombard, C J; Bateman, E D; Irusen, E M; Enarson, D A; Borgdorff, M W; Beyers, N

    2008-10-01

    Passive detection of tuberculosis (TB) cases may lead to delay in treatment which may contribute to increased severity of disease and mortality. Active case finding may be an alternative. In a community survey in Cape Town, South Africa, we actively detected 27 bacteriologically positive TB cases and compared those with 473 passively detected TB cases. Seven of 27 (26%) actively detected TB cases did not start treatment within 2 months and were considered initial defaulters. Those who did start treatment had similar treatment success rates as passively detected TB cases (both 80%) (OR 1.01, CI 0.33-3.09). Passively detected cases reported the presence of the symptoms cough (OR 3.72, 95% CI 1.47-9.39), haemoptysis (OR 3.20, 95% CI 1.03-9.93), night sweats (OR 3.35, 95% CI 1.40-7.99), fever (OR 4.28, 95% CI 1.21-15.14), and weight loss (OR 11.14, 95% CI 4.17-29.74) more often than those detected actively. We conclude that although TB cases detected by a community survey are less symptomatic and are prone to a high initial default rate, active case finding can potentially identify a substantial portion of the existing caseload at an earlier stage of disease, thereby reducing the risk of transmission.

  12. Longitudinal functional additive model with continuous proportional outcomes for physical activity data.

    PubMed

    Li, Haocheng; Kozey-Keadle, Sarah; Kipnis, Victor; Carroll, Raymond J

    2016-01-01

    Motivated by physical activity data obtained from the BodyMedia FIT device (www.bodymedia.com), we take a functional data approach for longitudinal studies with continuous proportional outcomes. The functional structure depends on three factors. In our three-factor model, the regression structures are specified as curves measured at various factor-points with random effects that have a correlation structure. The random curve for the continuous factor is summarized using a few important principal components. The difficulties in handling the continuous proportion variables are solved by using a quasilikelihood type approximation. We develop an efficient algorithm to fit the model, which involves the selection of the number of principal components. The method is evaluated empirically by a simulation study. This approach is applied to the BodyMedia data with 935 males and 84 consecutive days of observation, for a total of 78, 540 observations. We show that sleep efficiency increases with increasing physical activity, while its variance decreases at the same time.

  13. Enhanced anaerobic digestion of waste activated sludge digestion by the addition of zero valent iron.

    PubMed

    Feng, Yinghong; Zhang, Yaobin; Quan, Xie; Chen, Suo

    2014-04-01

    Anaerobic digestion is promising technology to recover energy from waste activated sludge. However, the sludge digestion is limited by its low efficiency of hydrolysis-acidification. Zero valent iron (ZVI) as a reducing material is expected to enhance anaerobic process including the hydrolysis-acidification process. Considering that, ZVI was added into an anaerobic sludge digestion system to accelerate the sludge digestion in this study. The results indicated that ZVI effectively enhanced the decomposition of protein and cellulose, the two main components of the sludge. Compared to the control test without ZVI, the degradation of protein increased 21.9% and the volatile fatty acids production increased 37.3% with adding ZVI. More acetate and less propionate are found during the hydrolysis-acidification with ZVI. The activities of several key enzymes in the hydrolysis and acidification increased 0.6-1 time. ZVI made the methane production raise 43.5% and sludge reduction ratio increase 12.2 percent points. Fluorescence in situ hybridization analysis showed that the abundances of hydrogen-consuming microorganisms including homoacetogens and hydrogenotrophic methanogens with ZVI were higher than the control, which reduced the H2 accumulation to create a beneficial condition for the sludge digestion in thermodynamics.

  14. Bactericidal activity of the food color additive Phloxine B against Staphylococcus aureus and other food borne microbial pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The spread of antibiotic resistance among Staphylococcus aureus strains requires the development of new anti S. aureus agents. The objective of this study was evaluating the antimicrobial activity of the food color additive Phloxine B against S. aureus and other food microbial pathogens. Our result ...

  15. A Pilot Study to Examine the Effect of Additional Structured Outdoor Playtime on Preschoolers' Physical Activity Levels

    ERIC Educational Resources Information Center

    Alhassan, Sofiya; Nwaokelemeh, Ogechi; Lyden, Kate; Goldsby, TaShauna; Mendoza, Albert

    2013-01-01

    The impact of additional structured outdoor playtime on preschoolers'; physical activity (PA) level is unclear. The purpose of this pilot study was to explore the effects of increasing structured outdoor playtime on preschoolers'; PA levels. Eight full-day classrooms (n = 134 children) from two preschool programmes were randomised into a treatment…

  16. Methanopyrus kandleri topoisomerase V contains three distinct AP lyase active sites in addition to the topoisomerase active site

    PubMed Central

    Rajan, Rakhi; Osterman, Amy; Mondragón, Alfonso

    2016-01-01

    Topoisomerase V (Topo-V) is the only topoisomerase with both topoisomerase and DNA repair activities. The topoisomerase activity is conferred by a small alpha-helical domain, whereas the AP lyase activity is found in a region formed by 12 tandem helix-hairpin-helix ((HhH)2) domains. Although it was known that Topo-V has multiple repair sites, only one had been mapped. Here, we show that Topo-V has three AP lyase sites. The atomic structure and Small Angle X-ray Scattering studies of a 97 kDa fragment spanning the topoisomerase and 10 (HhH)2 domains reveal that the (HhH)2 domains extend away from the topoisomerase domain. A combination of biochemical and structural observations allow the mapping of the second repair site to the junction of the 9th and 10th (HhH)2 domains. The second site is structurally similar to the first one and to the sites found in other AP lyases. The 3rd AP lyase site is located in the 12th (HhH)2 domain. The results show that Topo-V is an unusual protein: it is the only known protein with more than one (HhH)2 domain, the only known topoisomerase with dual activities and is also unique by having three AP lyase repair sites in the same polypeptide. PMID:26908655

  17. Methanopyrus kandleri topoisomerase V contains three distinct AP lyase active sites in addition to the topoisomerase active site.

    PubMed

    Rajan, Rakhi; Osterman, Amy; Mondragón, Alfonso

    2016-04-20

    Topoisomerase V (Topo-V) is the only topoisomerase with both topoisomerase and DNA repair activities. The topoisomerase activity is conferred by a small alpha-helical domain, whereas the AP lyase activity is found in a region formed by 12 tandem helix-hairpin-helix ((HhH)2) domains. Although it was known that Topo-V has multiple repair sites, only one had been mapped. Here, we show that Topo-V has three AP lyase sites. The atomic structure and Small Angle X-ray Scattering studies of a 97 kDa fragment spanning the topoisomerase and 10 (HhH)2 domains reveal that the (HhH)2 domains extend away from the topoisomerase domain. A combination of biochemical and structural observations allow the mapping of the second repair site to the junction of the 9th and 10th (HhH)2 domains. The second site is structurally similar to the first one and to the sites found in other AP lyases. The 3rd AP lyase site is located in the 12th (HhH)2 domain. The results show that Topo-V is an unusual protein: it is the only known protein with more than one (HhH)2 domain, the only known topoisomerase with dual activities and is also unique by having three AP lyase repair sites in the same polypeptide.

  18. The effect of loess addition on the settling ability of activated sludge.

    PubMed

    Wells, Miriam; Wareham, David G; Broady, Paul

    2015-01-01

    In this research, loess addition was investigated as a possible means of controlling the bulking sludge generated from a sequencing batch reactor (SBR) system treating a synthetic wastewater. The specific objective was to investigate whether loess changed the morphology of the sludge (i.e., influenced the relative abundance of filamentous species), as opposed to improving settling simply because the clay portion of the loess acted as a flocculating agent. To this end, two sets of batch tests were performed using 1 L reactors filled with bulking sludge from the SBR. The first set of batch tests investigated the effect of different loess concentration on the settling properties of the sludge; thus loess was added in concentrations of 0.0, 0.4, 2.0 and 5.0 g L(-1). The 5.0 g L(-1) loess concentration exhibited the most positive results on settling, bringing the modified sludge volume index (SVI) down into the target range of 150 mL g(-1). The second set of batch tests investigated filament length along with the modified SVI. It appeared that at the microbial level, 5.0 g L(-1)of loess caused no reduction in filament length, suggesting no reduction in the amount of filamentous microorganisms. This means that adding loess to a system after it has bulked has the potential to mask the bulking problem by improving settling, while not fixing the problem microbiologically.

  19. Addition of prothrombin to plasma can result in a paradoxical increase in activated partial thromboplastin time.

    PubMed

    Hansson, Kenny M; Björkqvist, Jenny; Deinum, Johanna

    2014-12-01

    In the activated partial thromboplastin time (APTT) assay, a variety of nonphysiological reagents is used to induce contact activation. The sensitivity of the APTT response for different thrombin inhibitors has previously been found to be dependent on the used reagent. Recently, infusion of prothrombin (FII) has been used in in-vivo coagulopathy models and its effect has been analyzed in different assays. Therefore, we investigated whether the FII plasma concentration might affect APTT using different commercial reagents, applying both turbidimetry and viscometry. We compared both plasma-derived human FII (pd-hFII) and recombinant human FII (r-hFII). Similar results were found for pd-hFII and r-hFII with different APTT reagents. As expected, no effect on APTT was found by increasing the plasma concentration of FII using APTT reagents consisting of ellagic acid (Actin FS or Actin). Although with Pathromtin SL, consisting of SiO2, only a slight increase was found, with most other commercial APTT reagents, consisting of SiO2 or kaolin, APTT dose-dependently increased by increasing concentration of FII. Therefore, both Pathromtin SL and Actin FS were used to compare r-hFII and pd-hFII by determining the KM at 37C using FII-depleted plasma, providing values of 6 ± 0.3 nmol/l FII for both. Thus, at normal plasma concentrations of FII, the maximal initial thrombin generation rate should be reached and no effect on the coagulation time is expected at higher FII concentrations. To completely avoid the paradoxical effect in the APTT assay at FII concentrations higher than normal, Actin or Actin FS is the preferable reagent.

  20. Amino acid addition to Vibrio cholerae LPS establishes a link between surface remodeling in gram-positive and gram-negative bacteria.

    PubMed

    Hankins, Jessica V; Madsen, James A; Giles, David K; Brodbelt, Jennifer S; Trent, M Stephen

    2012-05-29

    Historically, the O1 El Tor and classical biotypes of Vibrio cholerae have been differentiated by their resistance to the antimicrobial peptide polymyxin B. However, the molecular mechanisms associated with this phenotypic distinction have remained a mystery for 50 y. Both gram-negative and gram-positive bacteria modify their cell wall components with amine-containing substituents to reduce the net negative charge of the bacterial surface, thereby promoting cationic antimicrobial peptide resistance. In the present study, we demonstrate that V. cholerae modify the lipid A anchor of LPS with glycine and diglycine residues. This previously uncharacterized lipid A modification confers polymyxin resistance in V. cholerae El Tor, requiring three V. cholerae proteins: Vc1577 (AlmG), Vc1578 (AlmF), and Vc1579 (AlmE). Interestingly, the protein machinery required for glycine addition is reminiscent of the gram-positive system responsible for D-alanylation of teichoic acids. Such machinery was not thought to be used by gram-negative organisms. V. cholerae O1 El Tor mutants lacking genes involved in transferring glycine to LPS showed a 100-fold increase in sensitivity to polymyxin B. This work reveals a unique lipid A modification and demonstrates a charge-based remodeling strategy shared between gram-positive and gram-negative organisms.

  1. Improving the performance of an aerobic membrane bioreactor (MBR) treating pharmaceutical wastewater with powdered activated carbon (PAC) addition.

    PubMed

    Kaya, Yasemin; Bacaksiz, A Murat; Golebatmaz, Ugur; Vergili, Ilda; Gönder, Z Beril; Yilmaz, Gulsum

    2016-04-01

    In this study, the effects of organic loading rate (OLR) and the addition of powdered activated carbon (PAC) on the performance and membrane fouling of MBR were conducted to treat real pharmaceutical process wastewater. Over 145 days of operation, the MBR system was operated at OLRs ranging from 1 to 2 kg COD m(-3) day(-1) without sludge wasting. The addition of PAC provided an improvement in the flux, despite an increase in the OLR:PAC ratio. The results demonstrated that the hybrid PAC-MBR system maintained a reduced amount of membrane fouling and steadily increased the removal performance of etodolac. PAC addition reduced the deposition of extracellular polymeric substance and organic matter on the membrane surface and resulted an increase in COD removal even at higher OLRs with low PAC addition. Membrane fouling mechanisms were investigated using combined adsorption fouling models. Modified fouling index values and normalized mass transfer coefficient values indicated that predominant fouling mechanism was cake adsorption.

  2. Impacts of powdered activated carbon addition on trihalomethane formation reactivity of dissolved organic matter in membrane bioreactor effluent.

    PubMed

    Ma, Defang; Gao, Yue; Gao, Baoyu; Wang, Yan; Yue, Qinyan; Li, Qian

    2014-12-01

    Characteristics and trihalomethane (THM) formation reactivity of dissolved organic matter (DOM) in effluents from two membrane bioreactors (MBRs) with and without powdered activated carbon (PAC) addition (referred to as PAC/MBR and MBR, respectively) were examined to investigate the effects of PAC addition on THM formation of MBR effluent during chlorination. PAC addition increased the specific UV absorbance. Hydrophobic DOM especially hydrophobic acids in PAC/MBR effluent (50%) were more than MBR effluent (42%). DOM with molecular weight <1 kDa constituted 12% of PAC/MBR effluent DOM, which was less than that of MBR effluent (16%). Data obtained from excitation and emission matrix fluorescence spectroscopy revealed that PAC/MBR effluent DOM contained more simple aromatic protein, but had less fulvic acid-like and soluble microbial by-product-like. PAC addition reduced the formation of bromine-containing THMs during chlorination of effluents, but increased THM formation reactivity of effluent DOM.

  3. Effects of waste activated sludge and surfactant addition on primary sludge hydrolysis and short-chain fatty acids accumulation.

    PubMed

    Ji, Zhouying; Chen, Guanlan; Chen, Yinguang

    2010-05-01

    This paper focused on the effects of waste activated sludge (WAS) and surfactant sodium dodecylbenzene sulfonate (SDBS) addition on primary sludge (PS) hydrolysis and short-chain fatty acids (SCFA) accumulation in fermentation. The results showed that sludge hydrolysis, SCFA accumulation, NH(4)(+)-N and PO(4)(3-)-P release, and volatile suspended solids (VSS) reduction were increased by WAS addition to PS, which were further increased by the addition of SDBS to the mixture of PS and WAS. Acetic, propionic and valeric acids were the top three SCFA in all experiments. Also, the fermentation liquids of PS, PS+WAS, and PS+WAS+SDBS were added, respectively, to municipal wastewater to examine their effects on biological municipal wastewater treatment, and the enhancement of both wastewater nitrogen and phosphorus removals was observed compared with no fermentation liquid addition.

  4. Automated docking of {alpha}-(1,4)- and {alpha}-(1,6)-linked glucosyl trisaccharides in the glucoamylase active site

    SciTech Connect

    Countinho, P.M.; Reilly, P.J.; Dowd, M.K.

    1998-06-01

    Low-energy conformers of five {alpha}-(1,4)- and {alpha}-(1,6)-linked glucosyl trisaccharides were flexibly docked into the glucoamylase active site using AutoDock 2.2. To ensure that all significant conformational space was searched, the starting trisaccharide conformers for docking were all possible combinations of the corresponding disaccharide low-energy conformers. All docked trisaccharides occupied subsites {minus}1 and +1 in very similar modes to those of corresponding nonreducing-end disaccharides. For linear substrates, full binding at subsite +2 occurred only when the substrate reducing end was {alpha}-(1,4)-linked, with hydrogen-bonding with the hydroxy-methyl group being the only polar interaction there. Given the absence of other important interactions at this subsite, multiple substrate conformations are allowed. For the one docked branched substrate, steric hindrance in the {alpha}-(1,6)-glycosidic oxygen suggests that the active-site residues have to change position for hydrolysis to occur. Subsite +1 of the glucoamylase active site allows flexibility in binding but, at least in Aspergillus glucoamylases, subsite +2 selectively binds substrates {alpha}-(1,4)-linked between subsites +1 and +2. Enzyme engineering to limit substrate flexibility at subsite +2 could improve glucoamylase industrial properties.

  5. Anaerobic Activation of p-Cymene in Denitrifying Betaproteobacteria: Methyl Group Hydroxylation versus Addition to Fumarate

    PubMed Central

    Strijkstra, Annemieke; Trautwein, Kathleen; Jarling, René; Wöhlbrand, Lars; Dörries, Marvin; Reinhardt, Richard; Drozdowska, Marta; Golding, Bernard T.; Wilkes, Heinz

    2014-01-01

    The betaproteobacteria “Aromatoleum aromaticum” pCyN1 and “Thauera” sp. strain pCyN2 anaerobically degrade the plant-derived aromatic hydrocarbon p-cymene (4-isopropyltoluene) under nitrate-reducing conditions. Metabolite analysis of p-cymene-adapted “A. aromaticum” pCyN1 cells demonstrated the specific formation of 4-isopropylbenzyl alcohol and 4-isopropylbenzaldehyde, whereas with “Thauera” sp. pCyN2, exclusively 4-isopropylbenzylsuccinate and tentatively identified (4-isopropylphenyl)itaconate were observed. 4-Isopropylbenzoate in contrast was detected with both strains. Proteogenomic investigation of p-cymene- versus succinate-adapted cells of the two strains revealed distinct protein profiles agreeing with the different metabolites formed from p-cymene. “A. aromaticum” pCyN1 specifically produced (i) a putative p-cymene dehydrogenase (CmdABC) expected to hydroxylate the benzylic methyl group of p-cymene, (ii) two dehydrogenases putatively oxidizing 4-isopropylbenzyl alcohol (Iod) and 4-isopropylbenzaldehyde (Iad), and (iii) the putative 4-isopropylbenzoate-coenzyme A (CoA) ligase (Ibl). The p-cymene-specific protein profile of “Thauera” sp. pCyN2, on the other hand, encompassed proteins homologous to subunits of toluene-activating benzylsuccinate synthase (termed [4-isopropylbenzyl]succinate synthase IbsABCDEF; identified subunits, IbsAE) and protein homologs of the benzylsuccinate β-oxidation (Bbs) pathway (termed BisABCDEFGH; all identified except for BisEF). This study reveals that two related denitrifying bacteria employ fundamentally different peripheral degradation routes for one and the same substrate, p-cymene, with the two pathways apparently converging at the level of 4-isopropylbenzoyl-CoA. PMID:25261521

  6. Core-shell column Tanaka characterization and additional tests using active pharmaceutical ingredients.

    PubMed

    Ludvigsson, Jufang Wu; Karlsson, Anders; Kjellberg, Viktor

    2016-12-01

    In the last decade, core-shell particles have gained more and more attention in fast liquid chromatography separations due to their comparable performance with fully porous sub-2 μm particles and their significantly lower back pressure. Core-shell particles are made of a solid core surrounded by a shell of classic fully porous material. To embrace the developed core-shell column market and use these columns in pharmaceutical analytical applications, 17 core-shell C18 columns purchased from various vendors with various dimensions (50 mm × 2.1 mm to 100 mm × 3 mm) and particle sizes (1.6-2.7 μm) were characterized using Tanaka test protocols. Furthermore, four selected active pharmaceutical ingredients were chosen as test probes to investigate the batch to batch reproducibility for core-shell columns of particle size 2.6-2.7 μm, with dimension of 100 × 3 mm and columns of particle size 1.6 μm, with dimension 100 × 2.1 mm under isocratic elution. Columns of particle size 2.6-2.7 μm were also tested under gradient elution conditions. To confirm the claimed comparable efficiency of 2.6 μm core-shell particles as sub-2 μm fully porous particles, column performances of the selected core-shell columns were compared with BEH C18 , 1.7 μm, a fully porous column material as well.

  7. Evidence that Plasmodium falciparum chromosome end clusters are cross-linked by protein and are the sites of both virulence gene silencing and activation.

    PubMed

    Marty, Allison J; Thompson, Jennifer K; Duffy, Michael F; Voss, Till S; Cowman, Alan F; Crabb, Brendan S

    2006-10-01

    The malaria parasite Plasmodium falciparum undergoes antigenic variation through allelic exclusion and variant expression of surface proteins encoded by the var gene family. Regulation of var genes is under epigenetic control and involves reversible silencing and activation that requires the physical repositioning of a var locus into a transcriptionally permissive zone of the nuclear periphery. P. falciparum chromosome ends appear to aggregate into large perinuclear clusters which house both subtelomeric and chromosome central var genes. In this study we further define the composition of telomeric clusters using fluorescent in situ hybridization, and provide evidence that chromosome end clusters are formed by cross-linking protein. In addition, we demonstrate that a subtelomeric reporter gene and a var gene remain within clusters regardless of their transcriptional status. Our findings support a model whereby a highly localized structure dedicated to the activation of a single var gene can be housed within a gene dense chromosome end cluster that is otherwise transcriptionally silent.

  8. Cross-linked enzyme aggregates (CLEAs) of selected lipases: a procedure for the proper calculation of their recovered activity

    PubMed Central

    2013-01-01

    In the last few years, synthesis of carrier-free immobilized biocatalysts by cross-linking of enzyme aggregates has appeared as a promising technique. Cross-linked enzyme aggregates (CLEAs) present several interesting advantages over carrier-bound immobilized enzymes, such as highly concentrated enzymatic activity, high stability of the produced superstructure, important production costs savings by the absence of a support, and the fact that no previous purification of the enzyme is needed. However, the published literature evidences that a) much specific non-systematic exploratory work is being done and, b) recovered activity calculations in CLEAs still need to be optimized. In this context, this contribution presents results of an optimized procedure for the calculation of the activity retained by CLEAs, based on the comparison of their specific activity relative to their free enzyme counterparts. The protocol implies determination of precipitable protein content in commercial enzyme preparations through precipitation with ammonium sulphate and a protein co-feeder. The identification of linear ranges of activity versus concentration/amount of protein in the test reaction is also required for proper specific activity determinations. By use of mass balances that involve the protein initially added to the synthesis medium, and the protein remaining in the supernatant and washing solutions (these last derived from activity measurements), the precipitable protein present in CLEAs is obtained, and their specific activity can be calculated. In the current contribution the described protocol was applied to CLEAs of Thermomyces lanuginosa lipase, which showed a recovered specific activity of 11.1% relative to native lipase. The approach described is simple and can easily be extended to other CLEAs and also to carrier-bound immobilized enzymes for accurate determination of their retained activity. PMID:23663379

  9. Rhodamine 110-linked amino acids and peptides as substrates to measure caspase activity upon apoptosis induction in intact cells.

    PubMed

    Hug, H; Los, M; Hirt, W; Debatin, K M

    1999-10-19

    Caspases (cysteine aspartate-specific proteases) are a structurally related group of cysteine proteases that cleave peptide bonds following specific recognition sequences. They play a central role in activating apoptosis of vertebrate cells. To measure apoptosis induced by various stimuli and at an early apoptotic stage, caspases are an ideal target. This is especially the case when apoptotic cells have to be analyzed ex vivo before phagocytes remove them. A new and sensitive caspase assay is based on a substrate that contains only aspartate residues linked to rhodamine 110. With this and similar substrates, we are able to detect intracellular caspase activation by flow cytometry after apoptosis induction in intact hematopoetic cell lines.

  10. Linking subsurface to surface degassing at active volcanoes: A thermodynamic model with applications to Erebus volcano

    NASA Astrophysics Data System (ADS)

    Iacovino, Kayla

    2015-12-01

    Volcanic plumbing systems are the pathways through which volatiles are exchanged between the deep Earth and the atmosphere. The interplay of a multitude of processes occurring at various depths in the system dictates the composition and quantity of gas eventually erupted through volcanic vents. Here, a model is presented as a framework for interpreting surface volcanic gas measurements in terms of subsurface degassing processes occurring throughout a volcanic plumbing system. The model considers all possible sources of fluid from multiple depths, including degassing of dissolved volatiles during crystallization and/or decompression as recorded in melt inclusions plus any co-existing fluid phase present in a magma reservoir. The former is achieved by differencing melt inclusion volatile contents between groups of melt inclusions saturated at discrete depths. The latter is calculated using a thermodynamic model, which computes the composition of a C-O-H-S fluid in equilibrium with a melt given a minimum of five thermodynamic parameters commonly known for natural systems (T, P, fO2, either fH2 or one parameter for H2O, and either fS2 or one parameter for CO2). The calculated fluids are thermodynamically decompressed and run through a mixing model, which finds all possible mixtures of subsurface fluid that match the chemistry of surface gas within ±2.0 mol%. The method is applied to Mount Erebus (Antarctica), an active, intraplate volcano whose gas emissions, which emanate from an active phonolitic lava lake, have been well quantified by FTIR, UV spectroscopy, and multi-gas sensors over the last several decades. In addition, a well-characterized suite of lavas and melt inclusions, and petrological interpretations thereof, represent a wealth of knowledge about the shallow, intermediate, and deep parts of the Erebus plumbing system. The model has been used to calculate the compositions of seven C-O-H-S fluids that originate from four distinct regions within the Erebus

  11. Effect of addition of commercial grape seed tannins on phenolic composition, chromatic characteristics, and antioxidant activity of red wine.

    PubMed

    Neves, Ana C; Spranger, Maria I; Zhao, Yuqing; Leandro, Maria C; Sun, Baoshan

    2010-11-24

    The effect of addition of grape seed tannins on the phenolic composition, chromatic characteristics, and antioxidant activity of red wine was studied. Two highly pure commercial grape seed tannins (GSE100 and GSE300) were selected, and their phenolic compositions were determined. Two types of red wines were made with Castelão/Tinta Miúda (3/2, w/w) grapevine varieties by fermentation on skin using two different maceration times, which correspond to the wines rich and poor in polyphenols, respectively. Each of these wines was used for experimentation with the addition of GSE100 and GSE300 before and immediately after alcoholic fermentation. Phenolic composition, chromatic characteristics, and antioxidant activity of the finished red wines were analyzed by HPLC-DAD, CIElab 76 convention, and DPPH radical test, respectively. The results showed that the addition of grape seed tannins had obvious effects of increasing color intensity and antioxidant activity only in the wines poor in polyphenols. Although GSE300 contained much higher amounts of di- and trimer procyanidins and a lower amount of polymeric proanthocyanidins, it provided effects of increasing the color intensity and antioxidant activity of the wines poor in polyphenols similar to those of GSE100. Furthermore, GSE100 released more gallic acid to wines than GSE300, although no gallic acid was detected in GSE100. Tannins added after alcoholic fermentation had a better effect on phenolic composition of red wine than tannins added before alcoholic fermentation.

  12. Sulfur transfer and activation by ubiquitin-like modifier system Uba4•Urm1 link protein urmylation and tRNA thiolation in yeast

    PubMed Central

    Jüdes, André; Bruch, Alexander; Klassen, Roland; Helm, Mark; Schaffrath, Raffael

    2016-01-01

    Urm1 is a unique dual-function member of the ubiquitin protein family and conserved from yeast to man. It acts both as a protein modifier in ubiquitin-like urmylation and as a sulfur donor for tRNA thiolation, which in concert with the Elongator pathway forms 5-methoxy-carbonyl-methyl-2-thio (mcm5s2) modified wobble uridines (U34) in anticodons. Using Saccharomyces cerevisiae as a model to study a relationship between these two functions, we examined whether cultivation temperature and sulfur supply previously implicated in the tRNA thiolation branch of the URM1 pathway also contribute to proper urmylation. Monitoring Urm1 conjugation, we found urmylation of the peroxiredoxin Ahp1 is suppressed either at elevated cultivation temperatures or under sulfur starvation. In line with this, mutants with sulfur transfer defects that are linked to enzymes (Tum1, Uba4) required for Urm1 activation by thiocarboxylation (Urm1-COSH) were found to maintain drastically reduced levels of Ahp1 urmylation and mcm5s2U34 modification. Moreover, as revealed by site specific mutagenesis, the S-transfer rhodanese domain (RHD) in the E1-like activator (Uba4) crucial for Urm1-COSH formation is critical but not essential for protein urmylation and tRNA thiolation. In sum, sulfur supply, transfer and activation chemically link protein urmylation and tRNA thiolation. These are features that distinguish the ubiquitin-like modifier system Uba4•Urm1 from canonical ubiquitin family members and will help elucidate whether, in addition to their mechanistic links, the protein and tRNA modification branches of the URM1 pathway may also relate in function to one another. PMID:28357324

  13. Secondary Science Teachers' Use of Laboratory Activities: Linking Epistemological Beliefs, Goals, and Practices

    ERIC Educational Resources Information Center

    Kang, Nam-Hwa; Wallace, Carolyn S.

    2005-01-01

    The purpose of this study was to explore how science teachers' epistemological beliefs and teaching goals are related to their use of lab activities. Research questions include: (1) What are the teachers' epistemological beliefs pertaining to lab activities? (2) Why do the science teachers use lab activities? (3) How are the teachers'…

  14. N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias.

    PubMed

    Soto, Antonio G; Smith, Thomas H; Chen, Buxin; Bhattacharya, Supriyo; Cordova, Isabel Canto; Kenakin, Terry; Vaidehi, Nagarajan; Trejo, JoAnn

    2015-07-07

    Protease-activated receptor-1 (PAR1) is a G-protein-coupled receptor (GPCR) for the coagulant protease thrombin. Similar to other GPCRs, PAR1 is promiscuous and couples to multiple heterotrimeric G-protein subtypes in the same cell and promotes diverse cellular responses. The molecular mechanism by which activation of a given GPCR with the same ligand permits coupling to multiple G-protein subtypes is unclear. Here, we report that N-linked glycosylation of PAR1 at extracellular loop 2 (ECL2) controls G12/13 versus Gq coupling specificity in response to thrombin stimulation. A PAR1 mutant deficient in glycosylation at ECL2 was more effective at stimulating Gq-mediated phosphoinositide signaling compared with glycosylated wildtype receptor. In contrast, wildtype PAR1 displayed a greater efficacy at G12/13-dependent RhoA activation compared with mutant receptor lacking glycosylation at ECL2. Endogenous PAR1 rendered deficient in glycosylation using tunicamycin, a glycoprotein synthesis inhibitor, also exhibited increased PI signaling and diminished RhoA activation opposite to native receptor. Remarkably, PAR1 wildtype and glycosylation-deficient mutant were equally effective at coupling to Gi and β-arrestin-1. Consistent with preferential G12/13 coupling, thrombin-stimulated PAR1 wildtype strongly induced RhoA-mediated stress fiber formation compared with mutant receptor. In striking contrast, glycosylation-deficient PAR1 was more effective at increasing cellular proliferation, associated with Gq signaling, than wildtype receptor. These studies suggest that N-linked glycosylation at ECL2 contributes to the stabilization of an active PAR1 state that preferentially couples to G12/13 versus Gq and defines a previously unidentified function for N-linked glycosylation of GPCRs in regulating G-protein signaling bias.

  15. Revealing a Novel Otubain-Like Enzyme from Leishmania infantum with Deubiquitinating Activity toward K48-Linked Substrate

    PubMed Central

    Azevedo, Clênia S.; Guido, Bruna C.; Pereira, Jhonata L.; Nolasco, Diego O.; Corrêa, Rafael; Magalhães, Kelly G.; Motta, Flávia N.; Santana, Jaime M.; Grellier, Philippe; Bastos, Izabela M. D.

    2017-01-01

    Deubiquitinating enzymes (DUBs) play an important role in regulating a variety of eukaryotic processes. In this context, exploring the role of deubiquitination in Leishmania infantum could be a promising alternative to search new therapeutic targets for leishmaniasis. Here we present the first characterization of a DUB from L. infantum, otubain (OtuLi), and its localization within parasite. The recombinant OtuLi (rOtuLi) showed improved activity on lysine 48 (K48)-linked over K63-linked tetra-ubiquitin (Ub) and site-directed mutations on amino acids close to the catalytic site (F82) or involved in Ub interaction (L265 and F182) caused structural changes as shown by molecular dynamics, resulting in a reduction or loss of enzyme activity, respectively. Furthermore, rOtuLi stimulates lipid droplet biogenesis (an inflammatory marker) and induces IL-6 and TNF-α secretion in peritoneal macrophages, both proinflammatory cytokines. Our findings suggest that OtuLi is a cytoplasmic enzyme with K48-linked substrate specificity that could play a part in proinflammatory response in stimulated murine macrophages. PMID:28386537

  16. Tobacco etch virus protease retains its activity in various buffers and in the presence of diverse additives.

    PubMed

    Sun, Changsheng; Liang, Jiongqiu; Shi, Rui; Gao, Xuna; Zhang, Ruijuan; Hong, Fulin; Yuan, Qihang; Wang, Shengbin

    2012-03-01

    Tobacco etch virus (TEV) protease is widely used to remove tags from recombinant fusion proteins because of its stringent sequence specificity. It is generally accepted that the high concentrations of salts or other special agents in most protein affinity chromatography buffers can affect enzyme activity, including that of TEV protease. Consequently, tedious desalination or the substitution of standard TEV reaction buffer for elution buffer are often needed to ensure TEV protease activity when removing fusion tags after purifying target proteins using affinity chromatography. To address this issue, we used SOE PCR technology to synthesize a TEV protease gene with a codon pattern adapted to the codon usage bias of Escherichia coli, recovered the purified recombinant TEV protease, and examined its activity in various elution buffers commonly used in affinity chromatography as well as the effects of selected additives on its activity. Our results showed that the rTEV protease maintained high activity in all affinity chromatography elution buffers tested and tolerated high concentrations of additives commonly used in protein purification procedures, such as ethylene glycol, EGTA, Triton X-100, Tween-20, NP-40, CHAPS, urea, SDS, guanidine hydrochloride and β-mercaptoethanol. These results will facilitate the use of rTEV protease in removing tags from fusion proteins.

  17. Stable Isotope Probing: Linking Functional Activity to Specific Members of Microbial Communities

    SciTech Connect

    Kreuzer-Martin, Helen W.

    2007-03-12

    Abstract Linking organisms or groups of organisms to specific functions within natural environments is a fundamental challenge in microbial ecology. Advances in technology for manipulating and analyzing nucleic acids have made it possible to characterize the members of microbial communities without the intervention of laboratory culturing. Results from such studies have shown that the vast majority of soil organisms have never been cultured, highlighting the risks of culture-based approaches in community analysis. The development of culture-independent techniques for following the flow of substrates through microbial communities therefore represents an important advance. These techniques, collectively known as stable isotope probing (SIP), involve introducing a stable isotope-labeled substrate into a microbial community and following the fate of the substrate by detecting the appearance of the isotope in diagnostic molecules such as fatty acids and nucleic acids. The molecules in which the isotope label appears provide identifying information about the organism that incorporated the substrate. SIP allows direct observations of substrate assimilation in minimally disturbed communities, and thus represents an exciting new tool for linking microbial identity and function. The use of lipids or nucleic acids as the diagnostic molecule brings different strengths and weaknesses to the experimental approach, and necessitates the use of significantly different instrumentation and analytical techniques. This mini-review provides an overview of the lipid and nucleic acid approaches, discusses their strengths and weaknesses, gives examples of applications in various settings, and looks at prospects for the future of SIP technology.

  18. Attempts at the production of more selective antitumourals. Part II. The antineoplastic activity of cyclophosphazenes linked to spermine

    NASA Astrophysics Data System (ADS)

    Sournies, François; Labarre, Jean-François; Spreafico, Federico; Filippeschi, Stefania; Quan Jin, Xing

    1986-09-01

    In an attempt to design antitumour cyclophosphazenes of improved specificity by linking them to some natural tumour finders, we studied the binding of gem-N 3P 3Az 4Cl 2 to spermine. Synthesis, NMR and mass spectra of the vectorized drug (in which two N 3P 3Az 4 active principles are linked to spermine in a DISPIROBINO configuration) are described. Results obtained with this compound in 6 murine tumour systems (L1210 and P388 leukaemias, 3LL carcinoma, M5076 reticulum cell sarcoma, B16 melanoma and line 16 mammary carcinoma), are also described and compared with results previously obtained about the targeting of gem-N 3P 3Az 4Cl 2 through 1,3-diaminopropane and 1,4-diaminobutane (putrescine).

  19. Effects of addition of tissue-type plasminogen activator in in vitro fertilization medium on bovine embryo development and quality.

    PubMed

    Krania, F; Dovolou, E; Rekkas, C A; Theodosiadou, E K; Pappas, I; Amiridis, G S

    2015-02-01

    Plasminogen activators/Plasmin system plays pivotal role in regulating reproductive functions of mammals. Here, we examined the effects of modification of in vitro fertilization medium (IVF medium) with the addition of tissue-type plasminogen activator (t-PA), on bovine embryo development and quality, assessed by quantification of expression of various genes related to metabolism, oxidation, implantation and apoptosis. In addition, plasminogen activator activity (PAA) and plasminogen activator inhibition (PAI) were measured in the spent media. After conventional IVM, 2016 cumulus-oocyte complexes (COCs) were divided into four groups with modified composition of the IVF medium containing t-PA and/or its inhibitor epsilon-aminocaproic acid (control, t-PA, t-PA+ε-ACA, ε-ACA). Presumptive zygotes were cultured for 8 days in synthetic oviductal fluid (SOF) medium; gene expression studies were carried out on morulae and blastocysts. t-PA alone significantly suppressed cleavage and blastocyst formation rates, but this effect was neutralized by the addition of ε-ACA. PAA in the treated group was significantly reduced by ε-ACA, but without total elimination. Significant differences were detected in the expression of genes related to apoptosis and/or cell cycle arrest (BAX, BCL2L1, KAT2B) between embryos produced in t-PA-modified media and controls, giving an overall notion that the inferior developmental competence of treated embryos may be attributed to apoptotic phenomena induced by t-PA. In conclusion, it appears that excessive t-PA content in the IVF media, suppresses blastocyst formation rate, possibly due to induction of apoptotic phenomena.

  20. Evaluation of estrogenic activity of parabens and their chlorinated derivatives by using the yeast two-hybrid assay and the enzyme-linked immunosorbent assay.

    PubMed

    Terasaki, Masanori; Kamata, Ryo; Shiraishi, Fujio; Makino, Masakazu

    2009-01-01

    We assessed the estrogen agonist activities of 21 parabens and their chlorinated derivatives by using yeast two-hybrid assays incorporating either the human or medaka (Oryzias latipes) estrogen receptor alpha (hERalpha and medERalpha, respectively), and by using hERalpha competitive enzyme-linked immunosorbent assay (ER-ELISA). In the two-hybrid assay with hERalpha, five parabens and three chlorinated derivatives exhibited estrogenic activity, and their relative activity (17beta-estradiol [E2] = 1) ranged from 2.0 x 10(-5) to 2.0 x 10(-4), with the highest activity observed in i-butylparaben. In the medERalpha assay, six parabens and six chlorinated derivatives exhibited estrogenic activity and their relative activity ranged from 2.7 x 10(-5) to 3.5 x 10(-3), with the highest activity observed in benzylparaben, its monochlorinated derivative, i-butylparaben, and n-butylparaben. Although medERalpha demonstrated an activity to E2 that was three times lower than that demonstrated by hERalpha, medERalpha has a higher sensitivity to parabens than hERa (1.3-8.9 times). Five parabens and two chlorinated derivatives exhibited a binding affinity to ERa in the ER-ELISA; of the parabens, i-butylparaben exhibited the strongest binding affinity. The yeast two-hybrid assay and the ER-ELISA also revealed that many of the assayed chlorinated parabens were much weaker than the parent compound. In addition, the results mainly showed that parabens with a bulk substituent (e.g., i-butyl and benzyl groups) had a higher activity than those with a sterically small substituent. It is considered that derivatization masks the apparent estrogenic activity of parabens, but the resulting chlorinated compounds may represent a potential hazard and therefore other toxicity tests should be performed to determine the toxicity of the chlorinated derivatives.

  1. Increased anterior insula activity in anxious individuals is linked to diminished perceived control

    PubMed Central

    Alvarez, R P; Kirlic, N; Misaki, M; Bodurka, J; Rhudy, J L; Paulus, M P; Drevets, W C

    2015-01-01

    Individuals with high-trait anxiety frequently report decreased perceived control. However, it is unclear how these processes are instantiated at a neural level. Prior research suggests that individuals prone to anxiety may have exaggerated activity in the anterior insula and altered activity in the cingulate cortex during anticipation of aversive events. Thus, we hypothesized that anxiety proneness influences anterior insula activation during anticipation of unpredictable threat through decreased perceived control. Forty physically healthy adults underwent neuroimaging while they explored computer-simulated contexts associated either with or without the threat of an unpredictable shock. Skin conductance, anxiety ratings and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging were used to assess responses to threat versus no threat. Perceived control was measured using the Anxiety Control Questionnaire-Revised. Mediation analysis examined how anxiety proneness influenced BOLD activity. Anticipation of unpredictable threat resulted in increased skin conductance responses, anxiety ratings and enhanced activation in bilateral insula, anterior midcingulate cortex (aMCC) and bed nucleus of the stria terminalis. Individuals with greater anxiety proneness and less perceived control showed greater activity in dorsal anterior insula (dAI). Perceived control mediated the relationship between anxiety proneness and dAI activity. Increased dAI activity was associated with increased activity in aMCC, which correlated with increased exploratory behavior. Results provide evidence that exaggerated insula activation during the threat of unpredictable shock is directly related to low perceived control in anxiety-prone individuals. Perceived control thus may constitute an important treatment target to modulate insula activity during anxious anticipation in anxiety-disordered individuals. PMID:26125154

  2. Comparison of EMG activity on abdominal muscles during plank exercise with unilateral and bilateral additional isometric hip adduction.

    PubMed

    Kim, Soo-Yong; Kang, Min-Hyeok; Kim, Eui-Ryong; Jung, In-Gui; Seo, Eun-Young; Oh, Jae-Seop

    2016-10-01

    The aim of this study was to investigate the effects of additional isometric hip adduction during the plank exercise on the abdominal muscles. Twenty healthy young men participated in this study. Surface electromyography (EMG) was used to monitor the activity of the bilateral rectus abdominis (RA), the internal oblique (IO), and the external oblique (EO) muscles. The participants performed three types of plank exercise; the standard plank exercise, the plank exercise with bilateral isometric hip adduction, and the plank exercise with unilateral isometric hip adduction. All abdominal muscle activity was significantly increased during the plank exercise combined with the bilateral and unilateral isometric hip adduction compared with the standard plank exercise (p<0.05). Bilateral IO, EO, and left RA muscle activity was significantly increased during the unilateral isometric hip adduction compared with the bilateral isometric hip adduction (p<0.05). These findings suggest that additional isometric hip adduction during the plank exercise could be a useful method to enhance abdominal muscle activity. In particular, the unilateral isometric hip adduction is a more beneficial exercise than the bilateral isometric hip adduction.

  3. Temporal Links in Daily Activity Patterns between Coral Reef Predators and Their Prey

    PubMed Central

    Bosiger, Yoland J.; McCormick, Mark I.

    2014-01-01

    Few studies have documented the activity patterns of both predators and their common prey over 24 h diel cycles. This study documents the temporal periodicity of two common resident predators of juvenile reef fishes, Cephalopholis cyanostigma (rockcod) and Pseudochromis fuscus (dottyback) and compares these to the activity and foraging pattern of a common prey species, juvenile Pomacentrus moluccensis (lemon damselfish). Detailed observations of activity in the field and using 24 h infrared video in the laboratory revealed that the two predators had very different activity patterns. C. cyanostigma was active over the whole 24 h period, with a peak in feeding strikes at dusk and increased activity at both dawn and dusk, while P. fuscus was not active at night and had its highest strike rates at midday. The activity and foraging pattern of P. moluccensis directly opposes that of C. cyanostigma with individuals reducing strike rate and intraspecific aggression at both dawn and dusk, and reducing distance from shelter and boldness at dusk only. Juveniles examined were just outside the size-selection window of P. fuscus. We suggest that the relatively predictable diel behaviour of coral reef predators results from physiological factors such as visual sensory abilities, circadian rhythmicity, variation in hunting profitability, and predation risk at different times of the day. Our study suggests that the diel periodicity of P. moluccensis behaviour may represent a response to increased predation risk at times when both the ability to efficiently capture food and visually detect predators is reduced. PMID:25354096

  4. Motivation and Self-Perception Profiles and Links with Physical Activity in Adolescent Girls

    ERIC Educational Resources Information Center

    Biddle, Stuart J. H.; Wang, C. K. John

    2003-01-01

    Research shows a decline in participation in physical activity across the teenage years. It is important, therefore, to examine factors that might influence adolescent girl's likelihood of being physically active. This study used contemporary theoretical perspectives from psychology to assess a comprehensive profile of motivational and…

  5. Visual-Somatosensory Integration is Linked to Physical Activity Level in Older Adults.

    PubMed

    Mahoney, Jeannette R; Dumas, Kristina; Holtzer, Roee

    2015-01-01

    Studies examining multisensory integration (MSI) in aging consistently demonstrate greater reaction time (RT) facilitation in old compared to young adults, but often fail to determine the utility of MSI. The aim of the current experiment was to further elucidate the utility of MSI in aging by determining its relationship to physical activity level. 147 non-demented older adults (mean age 77 years; 57% female) participated. Participants were instructed to make speeded responses to visual, somatosensory, and visual-somatosensory (VS) stimuli. Depending on the magnitude of the individuals' RT facilitation, participants were classified into a MSI or NO MSI group. Physical activity was assessed using a validated physical activity scale. As predicted, RTs to VS stimuli were significantly shorter than those elicited to constituent unisensory conditions. Multisensory RT facilitation was a significant predictor of total number of physical activity days per month, with individuals in the NO MSI group reporting greater engagement in physical activities compared to those requiring greater RT facilitation.

  6. Addition of mucin to the growth medium triggers mucus-binding activity in different strains of Lactobacillus reuteri in vitro.

    PubMed

    Jonsson, H; Ström, E; Roos, S

    2001-10-16

    We have examined the ability of a number of Lactobacillus reuteri strains to bind immobilised mucus material. After growth in MRS broth, some strains showed high binding activity towards mucus whilst many strains exhibited a very low binding activity. In order to simulate the intestinal milieu, we grew the bacteria in MRS supplemented with the glycoprotein mucin, the main component of mucus. Growth under these conditions dramatically improved the mucus-binding activity of most strains that initially showed very poor binding when grown in MRS broth. In addition, there was a strong induction of mucus binding in some strains after growth on solid substrate as compared to growth in liquid culture. Protease treatment of bacteria grown in the presence of mucin eliminated the adhesion, suggesting that mucin induces the production of cell surface proteins that possess mucus-binding properties.

  7. What Makes Red Giants Tick? Linking Tidal Forces, Activity, and Solar-Like Oscillations via Eclipsing Binaries

    NASA Astrophysics Data System (ADS)

    Rawls, Meredith L.; Gaulme, Patrick; McKeever, Jean; Jackiewicz, Jason

    2016-01-01

    Thanks to advances in asteroseismology, red giants have become astrophysical laboratories for studying stellar evolution and probing the Milky Way. However, not all red giants show solar-like oscillations. It has been proposed that stronger tidal interactions from short-period binaries and increased magnetic activity on spotty giants are linked to absent or damped solar-like oscillations, yet each star tells a nuanced story. In this work, we characterize a subset of red giants in eclipsing binaries observed by Kepler. The binaries exhibit a range of orbital periods, solar-like oscillation behavior, and stellar activity. We use orbital solutions together with a suite of modeling tools to combine photometry and spectroscopy in a detailed analysis of tidal synchronization timescales, star spot activity, and stellar evolution histories. These red giants offer an unprecedented opportunity to test stellar physics and are important benchmarks for ensemble asteroseismology.

  8. Regulation of AMPK Activation by CD36 Links Fatty Acid Uptake to β-Oxidation

    PubMed Central

    Sun, Jingyu; Pietka, Terri; Gross, Richard W.; Eckel, Robert H.; Su, Xiong; Stahl, Philip D.

    2015-01-01

    Increases in muscle energy needs activate AMPK and induce sarcolemmal recruitment of the fatty acid (FA) translocase CD36. The resulting rises in FA uptake and FA oxidation are tightly correlated, suggesting coordinated regulation. We explored the possibility that membrane CD36 signaling might influence AMPK activation. We show, using several cell types, including myocytes, that CD36 expression suppresses AMPK, keeping it quiescent, while it mediates AMPK activation by FA. These dual effects reflect the presence of CD36 in a protein complex with the AMPK kinase LKB1 (liver kinase B1) and the src kinase Fyn. This complex promotes Fyn phosphorylation of LKB1 and its nuclear sequestration, hindering LKB1 activation of AMPK. FA interaction with CD36 dissociates Fyn from the protein complex, allowing LKB1 to remain cytosolic and activate AMPK. Consistent with this, CD36−/− mice have constitutively active muscle and heart AMPK and enhanced FA oxidation of endogenous triglyceride stores. The molecular mechanism described, whereby CD36 suppresses AMPK, with FA binding to CD36 releasing this suppression, couples AMPK activation to FA availability and would be important for the maintenance of cellular FA homeostasis. Its dysfunction might contribute to the reported association of CD36 variants with metabolic complications of obesity in humans. PMID:25157091

  9. Phosphorylation of histone H3 is functionally linked to retinoic acid receptor β promoter activation

    PubMed Central

    Lefebvre, Bruno; Ozato, Keiko; Lefebvre, Philippe

    2002-01-01

    Ligand-dependent transcriptional activation of retinoic acid receptors (RARs) is a multistep process culminating in the formation of a multimeric co-activator complex on regulated promoters. Several co-activator complexes harbor an acetyl transferase activity, which is required for retinoid-induced transcription of reporter genes. Using murine P19 embryonal carcinoma cells, we examined the relationship between histone post-translational modifications and activation of the endogenous RARβ2 promoter, which is under the control of a canonical retinoic acid response element and rapidly induced upon retinoid treatment. While histones H3 and H4 were constitutively acetylated at this promoter, retinoid agonists induced a rapid phosphorylation at Ser10 of histone H3. A retinoid antagonist, whose activity was independent of co-repressor binding to RAR, could oppose this agonist-induced H3 phosphorylation. Since such post-translational modifications were not observed at several other promoters, we conclude that histone H3 phosphorylation may be a molecular signature of the activated, retinoid-controlled mRARβ2 gene promoter. PMID:11897660

  10. From linked open data to molecular interaction: studying selectivity trends for ligands of the human serotonin and dopamine transporter† †The authors declare no competing interests. ‡ ‡Electronic supplementary information (ESI) available. See DOI: 10.1039/c6md00207b Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file.

    PubMed Central

    Hellsberg, Eva; Viereck, Michael; Ecker, Gerhard F.

    2016-01-01

    Retrieval of congeneric and consistent SAR data sets for protein targets of interest is still a laborious task to do if no appropriate in-house data set is available. However, combining integrated open data sources (such as the Open PHACTS Discovery Platform) with workflow tools now offers the possibility of querying across multiple domains and tailoring the search to the given research question. Starting from two phylogenetically related protein targets of interest (the human serotonin and dopamine transporters), the whole chemical compound space was explored by implementing a scaffold-based clustering of compounds possessing biological measurements for both targets. In addition, potential hERG blocking liabilities were included. The workflow allowed studying the selectivity trends of scaffold series, identifying potentially harmful compound series, and performing SAR, docking studies and molecular dynamics (MD) simulations for a consistent data set of 56 cathinones. This delivered useful insights into driving determinants for hDAT selectivity over hSERT. With respect to the scaffold-based analyses it should be noted that the cathinone data set could be retrieved only when Murcko scaffold analyses were combined with similarity searches such as a common substructure search. PMID:27891211

  11. Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk.

    PubMed

    Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

    2015-01-01

    Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.

  12. Linking canonical microcircuits and neuronal activity: Dynamic causal modelling of laminar recordings.

    PubMed

    Pinotsis, D A; Geerts, J P; Pinto, L; FitzGerald, T H B; Litvak, V; Auksztulewicz, R; Friston, K J

    2017-02-01

    Neural models describe brain activity at different scales, ranging from single cells to whole brain networks. Here, we attempt to reconcile models operating at the microscopic (compartmental) and mesoscopic (neural mass) scales to analyse data from microelectrode recordings of intralaminar neural activity. Although these two classes of models operate at different scales, it is relatively straightforward to create neural mass models of ensemble activity that are equipped with priors obtained after fitting data generated by detailed microscopic models. This provides generative (forward) models of measured neuronal responses that retain construct validity in relation to compartmental models. We illustrate our approach using cross spectral responses obtained from V1 during a visual perception paradigm that involved optogenetic manipulation of the basal forebrain. We find that the resulting neural mass model can distinguish between activity in distinct cortical layers - both with and without optogenetic activation - and that cholinergic input appears to enhance (disinhibit) superficial layer activity relative to deep layers. This is particularly interesting from the perspective of predictive coding, where neuromodulators are thought to boost prediction errors that ascend the cortical hierarchy.

  13. Design, modeling, synthesis and biological activity evaluation of camptothecin-linked platinum anticancer agents.

    PubMed

    Cincinelli, Raffaella; Musso, Loana; Dallavalle, Sabrina; Artali, Roberto; Tinelli, Stella; Colangelo, Donato; Zunino, Franco; De Cesare, Michelandrea; Beretta, Giovanni Luca; Zaffaroni, Nadia

    2013-05-01

    The design, modeling, synthesis and biological activity evaluation of two hybrid agents formed by 7-oxyiminomethylcamptothecin derivatives and diaminedichloro-platinum (II) complex are reported. The compounds showed growth inhibitory activity against a panel of human tumor cell lines, including sublines resistant to topotecan and platinum compounds. The derivatives were active in all the tested cell lines, and compound 1b, the most active one, was able to overcome cisplatin resistance in the osteosarcoma U2OS/Pt cell line. Platinum-containing camptothecins produced platinum-DNA adducts and topoisomerase I-mediated DNA damage with cleavage pattern and persistence similar to SN38, the active principle of irinotecan. Compound 1b exhibited an appreciable antitumor activity in vivo against human H460 tumor xenograft, comparable to that of irinotecan at lower well-tolerated dose levels and superior to cisplatin. The results support the interpretation that the diaminedichloro-platinum (II) complex conjugated via an oxyiminomethyl linker at the 7-position of the camptothecin resulted in a new class of effective antitumor compounds.

  14. Immune activity elevates energy expenditure of house sparrows: a link between direct and indirect costs?

    PubMed

    Martin, Lynn B; Scheuerlein, Alex; Wikelski, Martin

    2003-01-22

    The activation of an immune response is beneficial for organisms but may also have costs that affect fitness. Documented immune costs include those associated with acquisition of special nutrients, as well as immunopathology or autoimmunity. Here, we test whether an experimental induction of the immune system with a non-pathological stimulant can elevate energy turnover in passerine birds. We injected phytohaemagglutinin (PHA), a commonly used mitogen that activates the cell-mediated immune response, into the wing web of house sparrows, Passer domesticus. We then examined energetic costs resulting from this immune activity and related those costs to other physiological activities. We found that PHA injection significantly elevated resting metabolic rate (RMR) of challenged sparrows relative to saline controls. We calculated the total cost of this immune activity to be ca. 4.20 kJ per day (29% RMR), which is equivalent to the cost of production of half of an egg (8.23 kJ egg(-1)) in this species. We suggest that immune activity in wild passerines increases energy expenditure, which in turn may influence important life-history characteristics such as clutch size, timing of breeding or the scheduling of moult.

  15. A structure-activity relationship study on multi-heterocyclic molecules: two linked thiazoles are required for cytotoxic activity

    PubMed Central

    Kim, Seong Jong; Lin, Chun Chieh; Pan, Chung-Mao; Rananaware, Dimple P.; Ramsey, Deborah M.

    2013-01-01

    We report the synthesis, cytotoxicity, and phenotypic analysis of oxazole and thiazole containing fragments. Evaluating the optimal size and heterocycle for growth inhibition and apoptosis showed that activity required at least two thiazoles sequentially connected. This is the first detailed comparison of biological activity between multi-heterocyclic containing fragments. PMID:23524379

  16. Optimization of the thermophilic anaerobic co-digestion of pig manure, agriculture waste and inorganic additive through specific methanogenic activity.

    PubMed

    Jiménez, J; Cisneros-Ortiz, M E; Guardia-Puebla, Y; Morgan-Sagastume, J M; Noyola, A

    2014-01-01

    The anaerobic co-digestion of three wastes (manure, rice straw and clay residue, an inorganic additive) at different concentration levels and their interactive effects on methanogenic activity were investigated in this work at thermophilic conditions in order to enhance hydrolytic activity and methane production. A central composite design and the response surface methodology were applied for the optimization of specific methanogenic activity (SMA) by assessing their interaction effects with a reduced number of experiments. The results showed a significant interaction among the wastes on the SMA and confirmed that co-digestion enhances methane production. Rice straw apparently did not supply a significant amount of substrate to make a difference in SMA or methane yield. On the other hand, clay residue had a positive effect as an inorganic additive for stimulating the anaerobic process, based on its mineral content and its adsorbent properties for ammonia. Finally, the optimal conditions for achieving a thermophilic SMA value close to 1.4 g CH4-COD/g VSS · d(-1) were 20.3 gVSS/L of manure, 9.8 gVSS/L of rice straw and 3.3 gTSS/L of clay.

  17. Stability of phenolic compounds, antioxidant activity and colour through natural sweeteners addition during storage of sour cherry puree.

    PubMed

    Nowicka, Paulina; Wojdyło, Aneta

    2016-04-01

    The aim of this study was to describe the changes in phenolic compounds, antioxidant activity and colour of sour cherry puree supplemented with different natural sweeteners (sucrose, palm sugar, erythritol, xylitol, steviol glycoside, Luo Han Kuo), and natural prebiotic (inulin). A total of 18 types of polyphenolic compounds were assessed in the following sour cherry puree by LC-MS-QTof analysis, before and after 6 months of storage at 4 °C and 30 °C. Total phenolics determined by UPLC-PDA-FL was 1179.6 mg/100 g dm. In samples with addition of sweeteners the content of phenolic compounds ranged from 1133.1 (puree with steviol glycoside) to 725.6 mg/100 g dm (puree with erythritol), and the content of these compounds strongly affected on antioxidant activity. After 6-month storage, protective effects of some additives (palm sugar, erythritol, steviol glycoside, xylitol and inulin) on the polyphenol content, especially on anthocyanins and consequently on colour, and antioxidant activity were noticed. The results showed that some natural sweeteners might be interesting from a nutritional as well as commercial and pharmaceutical perspective.

  18. Alkali metals in addition to acidic pH activate the EvgS histidine kinase sensor in Escherichia coli.

    PubMed

    Eguchi, Yoko; Utsumi, Ryutaro

    2014-09-01

    Two-component signal transduction systems (TCSs) in bacteria perceive environmental stress and transmit the information via phosphorelay to adjust multiple cellular functions for adaptation. The EvgS/EvgA system is a TCS that confers acid resistance to Escherichia coli cells. Activation of the EvgS sensor initiates a cascade of transcription factors, EvgA, YdeO, and GadE, which induce the expression of a large group of acid resistance genes. We searched for signals activating EvgS and found that a high concentration of alkali metals (Na(+), K(+)) in addition to low pH was essential for the activation. EvgS is a histidine kinase, with a large periplasmic sensor region consisting of two tandem PBPb (bacterial periplasmic solute-binding protein) domains at its N terminus. The periplasmic sensor region of EvgS was necessary for EvgS activation, and Leu152, located within the first PBPb domain, was involved in the activation. Furthermore, chimeras of EvgS and PhoQ histidine kinases suggested that alkali metals were perceived at the periplasmic sensor region, whereas the cytoplasmic linker domain, connecting the transmembrane region and the histidine kinase domain, was required for low-pH perception.

  19. A subset of annular lipids is linked to the flippase activity of an ABC transporter.

    PubMed

    Bechara, Chérine; Nöll, Anne; Morgner, Nina; Degiacomi, Matteo T; Tampé, Robert; Robinson, Carol V

    2015-03-01

    Lipids are critical components of membranes that could affect the properties of membrane proteins, yet the precise compositions of lipids surrounding membrane-embedded protein complexes is often difficult to discern. Here we report that, for the heterodimeric ABC transporter TmrAB, the extent of delipidation can be controlled by timed exposure to detergent. We subsequently characterize the cohort of endogenous lipids that are extracted in contact with the membrane protein complex, and show that with prolonged delipidation the number of neutral lipids is reduced in favour of their negatively charged counterparts. We show that lipid A is retained by the transporter and that the extent of its binding decreases during the catalytic cycle, implying that lipid A release is linked to adenosine tri-phosphate hydrolysis. Together, these results enable us to propose that a subset of annular lipids is invariant in composition, with negatively charged lipids binding tightly to TmrAB, and imply a role for this exporter in glycolipid translocation.

  20. A subset of annular lipids is linked to the flippase activity of an ABC transporter

    NASA Astrophysics Data System (ADS)

    Bechara, Chérine; Nöll, Anne; Morgner, Nina; Degiacomi, Matteo T.; Tampé, Robert; Robinson, Carol V.

    2015-03-01

    Lipids are critical components of membranes that could affect the properties of membrane proteins, yet the precise compositions of lipids surrounding membrane-embedded protein complexes is often difficult to discern. Here we report that, for the heterodimeric ABC transporter TmrAB, the extent of delipidation can be controlled by timed exposure to detergent. We subsequently characterize the cohort of endogenous lipids that are extracted in contact with the membrane protein complex, and show that with prolonged delipidation the number of neutral lipids is reduced in favour of their negatively charged counterparts. We show that lipid A is retained by the transporter and that the extent of its binding decreases during the catalytic cycle, implying that lipid A release is linked to adenosine tri-phosphate hydrolysis. Together, these results enable us to propose that a subset of annular lipids is invariant in composition, with negatively charged lipids binding tightly to TmrAB, and imply a role for this exporter in glycolipid translocation.

  1. Characterization of a redox active cross-linked complex between cyanobacterial photosystem I and soluble ferredoxin.

    PubMed Central

    Lelong, C; Boekema, E J; Kruip, J; Bottin, H; Rögner, M; Sétif, P

    1996-01-01

    A covalent stoichiometric complex between photosystem I (PSI) and ferredoxin from the cyanobacterium Synechocystis sp. PCC 6803 was generated by chemical cross-linking. The photoreduction of ferredoxin, studied by laser flash absorption spectroscopy between 460 and 600 nm, is a fast process in 60% of the covalent complexes, which exhibit spectral and kinetic properties very similar to those observed with the free partners. Two major phases with t(1/2) <1 micros and approximately 10-14 micros are observed at two different pH values (5.8 and 8.0). The remaining complexes do not undergo fast ferredoxin reduction and 20-25% of the complexes are still able to reduce free ferredoxin or flavodoxin efficiently, thus indicating that ferredoxin is not bound properly in this proportion of covalent complexes. The docking site of ferredoxin on PSI was determined by electron microscopy in combination with image analysis. Ferredoxin binds to the cytoplasmic side of PSI, with its mass center 77 angstroms distant from the center of the trimer and in close contact with a ridge formed by the subunits PsaC, PsaD and PsaE. This docking site corresponds to a close proximity between the [2Fe- 2S] center of ferredoxin and the terminal [4Fe-4S] acceptor FII of PSI and is very similar in position to the docking site of flavodoxin, an alternative electron acceptor of PSI. Images PMID:8641281

  2. Visual–Somatosensory Integration is Linked to Physical Activity Level in Older Adults

    PubMed Central

    Mahoney, Jeannette R.; Dumas, Kristina; Holtzer, Roee

    2016-01-01

    Studies examining multisensory integration (MSI) in aging consistently demonstrate greater reaction time (RT) facilitation in old compared to young adults, but often fail to determine the utility of MSI. The aim of the current experiment was to further elucidate the utility of MSI in aging by determining its relationship to physical activity level. 147 non-demented older adults (mean age 77 years; 57% female) participated. Participants were instructed to make speeded responses to visual, somatosensory, and visual–somatosensory (VS) stimuli. Depending on the magnitude of the individuals’ RT facilitation, participants were classified into a MSI or NO MSI group. Physical activity was assessed using a validated physical activity scale. As predicted, RTs to VS stimuli were significantly shorter than those elicited to constituent unisensory conditions. Multisensory RT facilitation was a significant predictor of total number of physical activity days per month, with individuals in the NO MSI group reporting greater engagement in physical activities compared to those requiring greater RT facilitation. PMID:26152050

  3. Linking DNRA community structure and activity in a shallow lagoonal estuarine system

    PubMed Central

    Song, Bongkeun; Lisa, Jessica A.; Tobias, Craig R.

    2014-01-01

    Dissimilatory nitrate reduction to ammonium (DNRA) and denitrification are two nitrate respiration pathways in the microbial nitrogen cycle. Diversity and abundance of denitrifying bacteria have been extensively examined in various ecosystems. However, studies on DNRA bacterial diversity are limited, and the linkage between the structure and activity of DNRA communities has yet to be discovered. We examined the composition, diversity, abundance, and activities of DNRA communities at five sites along a salinity gradient in the New River Estuary, North Carolina, USA, a shallow temporal/lagoonal estuarine system. Sediment slurry incubation experiments with 15N-nitrate were conducted to measure potential DNRA rates, while the abundance of DNRA communities was calculated using quantitative PCR of nrfA genes encoding cytochrome C nitrite reductase, commonly found in DNRA bacteria. A pyrosequencing method targeting nrfA genes was developed using an Ion Torrent sequencer to examine the diversity and composition of DNRA communities within the estuarine sediment community. We found higher levels of nrfA gene abundance and DNRA activities in sediments with higher percent organic content. Pyrosequencing analysis of nrfA genes revealed spatial variation of DNRA communities along the salinity gradient of the New River Estuary. Percent abundance of dominant populations was found to have significant influence on overall activities of DNRA communities. Abundance of dominant DNRA bacteria and organic carbon availability are important regulators of DNRA activities in the eutrophic New River Estuary. PMID:25232351

  4. The effect of activated carbon addition on membrane bioreactor processes for wastewater treatment and reclamation - A critical review.

    PubMed

    Skouteris, George; Saroj, Devendra; Melidis, Paraschos; Hai, Faisal I; Ouki, Sabèha

    2015-06-01

    This review concentrates on the effect of activated carbon (AC) addition to membrane bioreactors (MBRs) treating wastewaters. Use of AC-assisted MBRs combines adsorption, biodegradation and membrane filtration. This can lead to advanced removal of recalcitrant pollutants and mitigation of membrane fouling. The relative contribution of adsorption and biodegradation to overall removal achieved by an AC-assisted MBR process can vary, and "biological AC" may not fully develop due to competition of target pollutants with bulk organics in wastewater. Thus periodic replenishment of spent AC is necessary. Sludge retention time (SRT) governs the frequency of spent AC withdrawal and addition of fresh AC, and is an important parameter that significantly influences the performance of AC-assisted MBRs. Of utmost importance is AC dosage because AC overdose may aggravate membrane fouling, increase sludge viscosity, impair mass transfer and reduce sludge dewaterability.

  5. The effect of ZnO addition on H2O activation over Co/ZrO2 catalysts

    SciTech Connect

    Davidson, Stephen D.; Sun, Junming; Wang, Yong

    2016-07-01

    The effect of ZnO addition on the dissociation of H2O and subsequent effects on cobalt oxidation state and ethanol reaction pathway were investigated over Co/ZrO2 catalyst during ethanol steam reforming (ESR). Catalyst physical properties were characterized by BET, XRD, and TEM. To characterize the catalysts ability to dissociate H2O, Raman spectroscopy, H2O-TPO, and pulsed H2O oxidation coupled with H2-TPR were used. It was found that the addition of ZnO to cobalt supported on ZrO2 decreased the activity for H2O dissociation, leading to a lower degree of cobalt oxidation. The decreased H2O dissociation was also found to affect the reaction pathway, evidenced by a shift in liquid product selectivity away from acetone and towards acetaldehyde.

  6. Impact of estrogenic compounds on DNA integrity in human spermatozoa: evidence for cross-linking and redox cycling activities.

    PubMed

    Bennetts, L E; De Iuliis, G N; Nixon, B; Kime, M; Zelski, K; McVicar, C M; Lewis, S E; Aitken, R J

    2008-05-10

    A great deal of circumstantial evidence has linked DNA damage in human spermatozoa with adverse reproductive outcomes including reduced fertility and high rates of miscarriage. Although oxidative stress is thought to make a significant contribution to DNA damage in the male germ line, the factors responsible for creating this stress have not been elucidated. One group of compounds that are thought to be active in this context are the estrogens, either generated as a result of the endogenous metabolism of androgens within the male reproductive tract or gaining access to the latter as a consequence of environmental exposure. In this study, a wide variety of estrogenic compounds were assessed for their direct effects on human spermatozoa in vitro. DNA integrity was assessed using the Comet and TUNEL assays, lesion frequencies were quantified by QPCR using targets within the mitochondrial and nuclear (beta-globin) genomes, DNA adducts were characterized by mass spectrometry and redox activity was monitored using dihydroethidium (DHE) as the probe. Of the estrogenic and estrogen analogue compounds evaluated, catechol estrogens, quercetin, diethylstilbestrol and pyrocatechol stimulated intense redox activity while genistein was only active at the highest doses tested. Other estrogens and estrogen analogues, such as 17beta-estradiol, nonylphenol, bisphenol A and 2,3-dihydroxynaphthalene were inactive. Estrogen-induced redox activity was associated with a dramatic loss of motility and, in the case of 2-hydroxyestradiol, the induction of significant DNA fragmentation. Mass spectrometry also indicated that catechol estrogens were capable of forming dimers that can cross-link the densely packed DNA strands in sperm chromatin, impairing nuclear decondensation. These results highlight the potential importance of estrogenic compounds in creating oxidative stress and DNA damage in the male germ line and suggest that further exploration of these compounds in the aetiology of male

  7. A visual pathway links brain structures active during magnetic compass orientation in migratory birds.

    PubMed

    Heyers, Dominik; Manns, Martina; Luksch, Harald; Güntürkün, Onur; Mouritsen, Henrik

    2007-09-26

    The magnetic compass of migratory birds has been suggested to be light-dependent. Retinal cryptochrome-expressing neurons and a forebrain region, "Cluster N", show high neuronal activity when night-migratory songbirds perform magnetic compass orientation. By combining neuronal tracing with behavioral experiments leading to sensory-driven gene expression of the neuronal activity marker ZENK during magnetic compass orientation, we demonstrate a functional neuronal connection between the retinal neurons and Cluster N via the visual thalamus. Thus, the two areas of the central nervous system being most active during magnetic compass orientation are part of an ascending visual processing stream, the thalamofugal pathway. Furthermore, Cluster N seems to be a specialized part of the visual wulst. These findings strongly support the hypothesis that migratory birds use their visual system to perceive the reference compass direction of the geomagnetic field and that migratory birds "see" the reference compass direction provided by the geomagnetic field.

  8. Linking Activation of Microglia and Peripheral Monocytic Cells to the Pathophysiology of Psychiatric Disorders

    PubMed Central

    Takahashi, Yuta; Yu, Zhiqian; Sakai, Mai; Tomita, Hiroaki

    2016-01-01

    A wide variety of studies have identified microglial activation in psychiatric disorders, such as schizophrenia, bipolar disorder, and major depressive disorder. Relatively fewer, but robust, studies have detected activation of peripheral monocytic cells in psychiatric disorders. Considering the origin of microglia, as well as neuropsychoimmune interactions in the context of the pathophysiology of psychiatric disorders, it is reasonable to speculate that microglia interact with peripheral monocytic cells in relevance with the pathogenesis of psychiatric disorders; however, these interactions have drawn little attention. In this review, we summarize findings relevant to activation of microglia and monocytic cells in psychiatric disorders, discuss the potential association between these cell types and disease pathogenesis, and propose perspectives for future research on these processes. PMID:27375431

  9. Enzymatically Regulated Peptide Pairing and Catalysis for the Bioanalysis of Extracellular Prometastatic Activities of Functionally Linked Enzymes

    NASA Astrophysics Data System (ADS)

    Li, Hao; Huang, Yue; Yu, Yue; Li, Tianqi; Li, Genxi; Anzai, Jun-Ichi

    2016-05-01

    Diseases such as cancer arise from systematical reconfiguration of interactions of exceedingly large numbers of proteins in cell signaling. The study of such complicated molecular mechanisms requires multiplexed detection of the inter-connected activities of several proteins in a disease-associated context. However, the existing methods are generally not well-equipped for this kind of application. Here a method for analyzing functionally linked protein activities is developed based on enzyme controlled pairing between complementary peptide helix strands, which simultaneously enables elaborate regulation of catalytic activity of the paired peptides. This method has been used to detect three different types of protein modification enzymes that participate in the modification of extracellular matrix and the formation of invasion front in tumour. In detecting breast cancer tissue samples using this method, up-regulated activity can be observed for two of the assessed enzymes, while the third enzyme is found to have a subtle fluctuation of activity. These results may point to the application of this method in evaluating prometastatic activities of proteins in tumour.

  10. Enzymatically Regulated Peptide Pairing and Catalysis for the Bioanalysis of Extracellular Prometastatic Activities of Functionally Linked Enzymes

    PubMed Central

    Li, Hao; Huang, Yue; Yu, Yue; Li, Tianqi; Li, Genxi; Anzai, Jun-ichi

    2016-01-01

    Diseases such as cancer arise from systematical reconfiguration of interactions of exceedingly large numbers of proteins in cell signaling. The study of such complicated molecular mechanisms requires multiplexed detection of the inter-connected activities of several proteins in a disease-associated context. However, the existing methods are generally not well-equipped for this kind of application. Here a method for analyzing functionally linked protein activities is developed based on enzyme controlled pairing between complementary peptide helix strands, which simultaneously enables elaborate regulation of catalytic activity of the paired peptides. This method has been used to detect three different types of protein modification enzymes that participate in the modification of extracellular matrix and the formation of invasion front in tumour. In detecting breast cancer tissue samples using this method, up-regulated activity can be observed for two of the assessed enzymes, while the third enzyme is found to have a subtle fluctuation of activity. These results may point to the application of this method in evaluating prometastatic activities of proteins in tumour. PMID:27140831

  11. Addition of Selenium Nanoparticles to Electrospun Silk Scaffold Improves the Mammalian Cell Activity While Reducing Bacterial Growth

    PubMed Central

    Chung, Stanley; Ercan, Batur; Roy, Amit K.; Webster, Thomas J.

    2016-01-01

    Silk possesses many beneficial wound healing properties, and electrospun scaffolds are especially applicable for skin applications, due to their smaller interstices and higher surface areas. However, purified silk promotes microbial growth. Selenium nanoparticles have shown excellent antibacterial properties and are a novel antimicrobial chemistry. Here, electrospun silk scaffolds were doped with selenium nanoparticles to impart antibacterial properties to the silk scaffolds. Results showed significantly improved bacterial inhibition and mild improvement in human dermal fibroblast metabolic activity. These results suggest that the addition of selenium nanoparticles to electrospun silk is a promising approach to improve wound healing with reduced infection, without relying on antibiotics. PMID:27471473

  12. AR intragenic deletions linked to androgen receptor splice variant expression and activity in models of prostate cancer progression.

    PubMed

    Li, Y; Hwang, T H; Oseth, L A; Hauge, A; Vessella, R L; Schmechel, S C; Hirsch, B; Beckman, K B; Silverstein, K A; Dehm, S M

    2012-11-08

    Reactivation of the androgen receptor (AR) during androgen depletion therapy (ADT) underlies castration-resistant prostate cancer (CRPCa). Alternative splicing of the AR gene and synthesis of constitutively active COOH-terminally truncated AR variants lacking the AR ligand-binding domain has emerged as an important mechanism of ADT resistance in CRPCa. In a previous study, we demonstrated that altered AR splicing in CRPCa 22Rv1 cells was linked to a 35-kb intragenic tandem duplication of AR exon 3 and flanking sequences. In this study, we demonstrate that complex patterns of AR gene copy number imbalances occur in PCa cell lines, xenografts and clinical specimens. To investigate whether these copy number imbalances reflect AR gene rearrangements that could be linked to splicing disruptions, we carried out a detailed analysis of AR gene structure in the LuCaP 86.2 and CWR-R1 models of CRPCa. By deletion-spanning PCR, we discovered a 8579-bp deletion of AR exons 5, 6 and 7 in the LuCaP 86.2 xenograft, which provides a rational explanation for synthesis of the truncated AR v567es AR variant in this model. Similarly, targeted resequencing of the AR gene in CWR-R1 cells led to the discovery of a 48-kb deletion in AR intron 1. This intragenic deletion marked a specific CWR-R1 cell population with enhanced expression of the truncated AR-V7/AR3 variant, a high level of androgen-independent AR transcriptional activity and rapid androgen independent growth. Together, these data demonstrate that structural alterations in the AR gene are linked to stable gain-of-function splicing alterations in CRPCa.

  13. Object relations theory and activity theory: a proposed link by way of the procedural sequence model.

    PubMed

    Ryle, A

    1991-12-01

    An account of object relations theory (ORT), represented in terms of the procedural sequence model (PSM), is compared to the ideas of Vygotsky and activity theory (AT). The two models are seen to be compatible and complementary and their combination offers a satisfactory account of human psychology, appropriate for the understanding and integration of psychotherapy.

  14. Impaired autophagy activity is linked to elevated ER-stress and inflammation in aging adipose tissue

    PubMed Central

    Ghosh, Amiya Kumar; Mau, Theresa; O'Brien, Martin; Garg, Sanjay; Yung, Raymond

    2016-01-01

    Adipose tissue dysfunction in aging is associated with inflammation, metabolic syndrome and other diseases. We propose that impaired protein homeostasis due to compromised lysosomal degradation (micro-autophagy) might promote aberrant ER stress response and inflammation in aging adipose tissue. Using C57BL/6 mouse model, we demonstrate that adipose tissue-derived stromal vascular fraction (SVF) cells from old (18-20 months) mice have reduced expression of autophagy markers as compared to the younger (4-6 months) cohort. Elevated expressions of ER-stress marker CHOP and autophagy substrate SQSTM1/p62 are observed in old SVFs compared to young, when treated with either vehicle or with thapsigargin (Tg), an ER stress inducer. Treatment with bafilomycin A1 (Baf), a vacuolar-type H (+)-ATPase, or Tg elevated expressions of CHOP, and SQSTM1/p62 and LC-3-II, in 3T3-L1-preadipocytes. We also demonstrate impaired autophagy activity in old SVFs by analyzing increased accumulation of autophagy substrates LC3-II and p62. Compromised autophagy activity in old SVFs is correlated with enhanced release of pro-inflammatory cytokines IL-6 and MCP-1. Finally, SVFs from calorie restricted old mice (CR-O) have shown enhanced autophagy activity compared to ad libitum fed old mice (AL-O). Our results support the notion that diminished autophagy activity with aging contributes to increased adipose tissue ER stress and inflammation. PMID:27777379

  15. Direction of Biological Motion Affects Early Brain Activation: A Link with Social Cognition

    PubMed Central

    Pegna, Alan John; Gehring, Elise; Meyer, Georg; Del Zotto, Marzia

    2015-01-01

    A number of EEG studies have investigated the time course of brain activation for biological movement over this last decade, however the temporal dynamics of processing are still debated. Moreover, the role of direction of movement has not received much attention even though it is an essential component allowing us to determine the intentions of the moving agent, and thus permitting the anticipation of potential social interactions. In this study, we examined event-related responses (ERPs) in 15 healthy human participants to light point walkers and their scrambled counterparts, whose movements occurred either in the radial or in the lateral plane. Compared to scrambled motion (SM), biological motion (BM) showed an enhanced negativity between 210 and 360ms. A source localization algorithm (sLORETA) revealed that this was due to an increase in superior and middle temporal lobe activity. Regarding direction, we found that radial BM produced an enhanced P1 compared to lateral BM, lateral SM and radial SM. This heightened P1 was due to an increase in activity in extrastriate regions, as well as in superior temporal, medial parietal and medial prefrontal areas. This network is known to be involved in decoding the underlying intentionality of the movement and in the attribution of mental states. The social meaning signaled by the direction of biological motion therefore appears to trigger an early response in brain activity. PMID:26121591

  16. Bridging the Gap: Linking Co-Curricular Activities to Student Learning Outcomes in Community College Students

    ERIC Educational Resources Information Center

    Storey, Katie Lauren

    2010-01-01

    This study investigated the extent to which participation in co-curricular events enhances the achievement of student-learning outcomes in community college students. One community college in Illinois--Chicago Metropolitan Area Community College (CMACC), a pseudonym--was selected to research based on its robust co-curricular activity programming.…

  17. Tomato fruit ascorbic acid content is linked with monodehydroascorbate reductase activity and tolerance to chilling stress.

    PubMed

    Stevens, R; Page, D; Gouble, B; Garchery, C; Zamir, D; Causse, M

    2008-08-01

    Quantitative trait loci (QTL) mapping is a step towards the identification of factors regulating traits such as fruit ascorbic acid content. A previously identified QTL controlling variations in tomato fruit ascorbic acid has been fine mapped and reveals that the QTL has a polygenic and epistatic architecture. A monodehydroascorbate reductase (MDHAR) allele is a candidate for a proportion of the increase in fruit ascorbic acid content. The MDHAR enzyme is active in different stages of fruit ripening, shows increased activity in the introgression lines containing the wild-type (Solanum pennellii) allele, and responds to chilling injury in tomato along with the reduced/oxidized ascorbate ratio. Low temperature storage of different tomato introgression lines with all or part of the QTL for ascorbic acid and with or without the wild MDHAR allele shows that enzyme activity explains 84% of the variation in the reduced ascorbic acid levels of tomato fruit following storage at 4 degrees C, compared with 38% at harvest under non-stress conditions. A role is indicated for MDHAR in the maintenance of ascorbate levels in fruit under stress conditions. Furthermore, an increased fruit MDHAR activity and a lower oxidation level of the fruit ascorbate pool are correlated with decreased loss of firmness because of chilling injury.

  18. Links between Adolescent Physical Activity, Body Mass Index, and Adolescent and Parent Characteristics

    ERIC Educational Resources Information Center

    Williams, Susan Lee; Mummery, W. Kerry

    2011-01-01

    Identification of the relationships between adolescent overweight and obesity and physical activity and a range of intrapersonal and interpersonal factors is necessary to develop relevant interventions which target the health needs of adolescents. This study examined adolescent body mass index (BMI) and participation in moderate and vigorous…

  19. Linked color imaging improves endoscopic diagnosis of active Helicobacter pylori infection

    PubMed Central

    Dohi, Osamu; Yagi, Nobuaki; Onozawa, Yuriko; Kimura-Tsuchiya, Reiko; Majima, Atsushi; Kitaichi, Tomoko; Horii, Yusuke; Suzuki, Kentaro; Tomie, Akira; Okayama, Tetsuya; Yoshida, Naohisa; Kamada, Kazuhiro; Katada, Kazuhiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Handa, Osamu; Konishi, Hideyuki; Naito, Yuji; Itoh, Yoshito

    2016-01-01

    Background and study aims: Linked color imaging (LCI) is a new image-enhanced endoscopy technique using a laser light source to enhance slight differences in mucosal color. The aim of this study was to compare the usefulness of LCI and conventional white light imaging (WLI) endoscopy for diagnosing Helicobacter pylori (H. pylori). Patients and methods: We retrospectively analyzed images from 60 patients examined with WLI and LCI endoscopy between October 2013 and May 2014. Thirty patients had H. pylori infections, and other thirty patients tested negative for H. pylori after eradication therapy. Four endoscopists evaluated the 2 types of images to determine which was better at facilitating a diagnosis of H. pylori infection. Results: H. pylori infection was identified with LCI by enhancing the red appearance of the fundic gland mucosa. The accuracy, sensitivity, and specificity for diagnosing H. pylori infection using WLI were 74.2 %, 81.7 %, and 66.7 %, respectively, while those for LCI were 85.8 %, 93.3 %, and 78.3 %, respectively. Thus, the accuracy and sensitivity for LCI were significantly higher than those for WLI (P = 0.002 and P = 0.011, respectively). The kappa values for the inter- and intraobserver variability among the 4 endoscopists were higher for LCI than for WLI. Conclusions: H. pylori infection can be identified by enhancing endoscopic images of the diffuse redness of the fundic gland using LCI. LCI is a novel image-enhanced endoscopy and is more useful for diagnosing H. pylori infection than is WLI. PMID:27556101

  20. Presenilin 1 is linked with γ-secretase activity in the detergent solubilized state

    PubMed Central

    Li, Yue-Ming; Lai, Ming-Tain; Xu, Min; Huang, Qian; DiMuzio-Mower, Jillian; Sardana, Mohinder K.; Shi, Xiao-Ping; Yin, Kuo-Chang; Shafer, Jules A.; Gardell, Stephen J.

    2000-01-01

    γ-Secretase is a membrane-associated protease that cleaves within the transmembrane region of amyloid precursor protein to generate the C termini of the two Aβ peptide isoforms, Aβ40 and Aβ42. Here we report the detergent solubilization and partial characterization of γ-secretase. The activity of solubilized γ-secretase was measured with a recombinant substrate, C100Flag, consisting largely of the C-terminal fragment of amyloid precursor protein downstream of the β-secretase cleavage site. Cleavage of C100Flag by γ-secretase was detected by electrochemiluminescence using antibodies that specifically recognize the Aβ40 or Aβ42 termini. Incubation of C100Flag with HeLa cell membranes or detergent-solubilized HeLa cell membranes generates both the Aβ40 and Aβ42 termini. Recovery of catalytically competent, soluble γ-secretase critically depends on the choice of detergent; CHAPSO (3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate) but not Triton X-100 is suitable. Solubilized γ-secretase activity is inhibited by pepstatin and more potently by a novel aspartyl protease transition-state analog inhibitor that blocks formation of Aβ40 and Aβ42 in mammalian cells. Upon gel exclusion chromatography, solubilized γ-secretase activity coelutes with presenilin 1 (PS1) at an apparent relative molecular weight of approximately 2.0 × 106. Anti-PS1 antibody immunoprecipitates γ-secretase activity from the solubilized γ-secretase preparation. These data suggest that γ-secretase activity is catalyzed by a PS1-containing macromolecular complex. PMID:10801983

  1. Physical Activity and Health Perception in Aging: Do Body Mass and Satisfaction Matter? A Three-Path Mediated Link

    PubMed Central

    Capranica, Laura; Stager, Joel; Forte, Roberta; Falbo, Simone; Di Baldassarre, Angela; Segura-Garcia, Cristina; Pesce, Caterina

    2016-01-01

    Although ageing people could benefit from healthy diet and physical activity to maintain health and quality of life, further understandings of the diet- and physical activity-related mechanisms that may cause changes in health and quality of life perception are necessary. The purpose of the study was to investigate the effect of eating attitudes, body mass and image satisfaction, and exercise dependence in the relationship between physical activity and health and quality of life perception in older individuals. Hundred and seventy-nine late middle-aged, (55–64 yrs), young-old (65–74 yrs), and old (75–84 yrs) senior athletes (n = 56), physically active (n = 58) or sedentary adults (n = 65) were submitted to anthropometric evaluations (body mass, height) and self-reported questionnaires: Body Image Dimensional Assessment, Exercise Dependence Scale, Eating Attitude Test, and Short Form Health Survey (Physical Component Summary [PCS] and Mental Component Summary [MCS] of and health and quality of life perception). Senior athletes, physically active, and sedentary participants subgroups differed (P<0.05) from each other in body mass index (BMI) and several components of body image and exercise dependence. Senior athletes showed, compared to their sedentary counterparts, further differences (P<0.05) in eating attitudes and in both PCS and MCS. Mediation analysis showed that the relationship between physical activity habit and MCS, but not PCS, was indirectly explained by a serial mediation chain composed of objective BMI and subjective body image (dis)satisfaction. Findings confirm the relevant role of physically active life habits for older individuals to perceive good physical and mental health. The novelty of the three-path mediated link between physical activity level and mental health perception suggests that the beneficial effect of a physically active lifestyle on weight control can positively impinge on the cognitive-emotional dimension of mental health by

  2. Activity of the Human Rhinovirus 3C Protease Studied in Various Buffers, Additives and Detergents Solutions for Recombinant Protein Production

    PubMed Central

    Tufail, Soban; Ismat, Fouzia; Imran, Muhammad; Iqbal, Mazhar; Mirza, Osman; Rhaman, Moazur

    2016-01-01

    Proteases are widely used to remove affinity and solubility tags from recombinant proteins to avoid potential interference of these tags with the structure and function of the fusion partner. In recent years, great interest has been seen in use of the human rhinovirus 3C protease owing to its stringent sequence specificity and enhanced activity. Like other proteases, activity of the human rhinovirus 3C protease can be affected in part by the buffer components and additives that are generally employed for purification and stabilization of proteins, hence, necessitate their removal by tedious and time-consuming procedures before proteolysis can occur. To address this issue, we examined the effect of elution buffers used for common affinity based purifications, salt ions, stability/solubility and reducing agents, and detergents on the activity of the human rhinovirus 3C protease using three different fusion proteins at 4°C, a temperature of choice for purification of many proteins. The results show that the human rhinovirus 3C protease performs better at 4°C than the frequently used tobacco etch virus protease and its activity was insensitive to most of the experimental conditions tested. Though number of fusion proteins tested is limited, we expect that these finding will facilitate the use of the human rhinovirus 3C protease in recombinant protein production for pharmaceutical and biotechnological applications. PMID:27093053

  3. Activity of the Human Rhinovirus 3C Protease Studied in Various Buffers, Additives and Detergents Solutions for Recombinant Protein Production.

    PubMed

    Ullah, Raheem; Shah, Majid Ali; Tufail, Soban; Ismat, Fouzia; Imran, Muhammad; Iqbal, Mazhar; Mirza, Osman; Rhaman, Moazur

    2016-01-01

    Proteases are widely used to remove affinity and solubility tags from recombinant proteins to avoid potential interference of these tags with the structure and function of the fusion partner. In recent years, great interest has been seen in use of the human rhinovirus 3C protease owing to its stringent sequence specificity and enhanced activity. Like other proteases, activity of the human rhinovirus 3C protease can be affected in part by the buffer components and additives that are generally employed for purification and stabilization of proteins, hence, necessitate their removal by tedious and time-consuming procedures before proteolysis can occur. To address this issue, we examined the effect of elution buffers used for common affinity based purifications, salt ions, stability/solubility and reducing agents, and detergents on the activity of the human rhinovirus 3C protease using three different fusion proteins at 4°C, a temperature of choice for purification of many proteins. The results show that the human rhinovirus 3C protease performs better at 4°C than the frequently used tobacco etch virus protease and its activity was insensitive to most of the experimental conditions tested. Though number of fusion proteins tested is limited, we expect that these finding will facilitate the use of the human rhinovirus 3C protease in recombinant protein production for pharmaceutical and biotechnological applications.

  4. Combinatorial therapeutic activation with heparin and AICAR stimulates additive effects on utrophin A expression in dystrophic muscles.

    PubMed

    Péladeau, Christine; Ahmed, Aatika; Amirouche, Adel; Crawford Parks, Tara E; Bronicki, Lucas M; Ljubicic, Vladimir; Renaud, Jean-Marc; Jasmin, Bernard J

    2016-01-01

    Upregulation of utrophin A is an attractive therapeutic strategy for treating Duchenne muscular dystrophy (DMD). Over the years, several studies revealed that utrophin A is regulated by multiple transcriptional and post-transcriptional mechanisms, and that pharmacological modulation of these pathways stimulates utrophin A expression in dystrophic muscle. In particular, we recently showed that activation of p38 signaling causes an increase in the levels of utrophin A mRNAs and protein by decreasing the functional availability of the destabilizing RNA-binding protein called K-homology splicing regulatory protein, thereby resulting in increases in the stability of existing mRNAs. Here, we treated 6-week-old mdx mice for 4 weeks with the clinically used anticoagulant drug heparin known to activate p38 mitogen-activated protein kinase, and determined the impact of this pharmacological intervention on the dystrophic phenotype. Our results show that heparin treatment of mdx mice caused a significant ∼1.5- to 3-fold increase in utrophin A expression in diaphragm, extensor digitorum longus and tibialis anterior (TA) muscles. In agreement with these findings, heparin-treated diaphragm and TA muscle fibers showed an accumulation of utrophin A and β-dystroglycan along their sarcolemma and displayed improved morphology and structural integrity. Moreover, combinatorial drug treatment using both heparin and 5-amino-4-imidazolecarboxamide riboside (AICAR), the latter targeting 5' adenosine monophosphate-activated protein kinase and the transcriptional activation of utrophin A, caused an additive effect on utrophin A expression in dystrophic muscle. These findings establish that heparin is a relevant therapeutic agent for treating DMD, and illustrate that combinatorial treatment of heparin with AICAR may serve as an effective strategy to further increase utrophin A expression in dystrophic muscle via activation of distinct signaling pathways.

  5. Activation of IFN-beta element by IRF-1 requires a posttranslational event in addition to IRF-1 synthesis.

    PubMed Central

    Watanabe, N; Sakakibara, J; Hovanessian, A G; Taniguchi, T; Fujita, T

    1991-01-01

    Expression of the Type I IFN (i.e., IFN-alpha s and IFN-beta) genes is efficiently induced by viruses at the transcriptional level. This induction is mediated by at least two types of positive regulatory elements located in the human IFN-beta gene promoter: (1) the repeated elements which bind both the transcriptional activator IRF-1 and the repressor IRF-2 (IRF-elements; IRF-Es), and (2) the kappa B element (kappa B-E), which binds NF kappa B and is located between the IRF-Es and the TATA box. In this study we demonstrate that a promoter containing synthetic IRF-E, which displays high affinity for the IRFs can be efficiently activated by Newcastle disease virus (NDV). In contrast, such activation was either very weak or nil when cells were treated by IFN-beta or tumor necrosis factor-alpha (TNF-alpha), despite the fact they both efficiently induce de novo synthesis of the short-lived IRF-1 in L929 cells. In fact, efficient activation of the IRF-E apparently requires an event in addition to de novo IRF-1 induction, which can be elicited by NDV even in the presence of protein synthesis inhibitor, cycloheximide. Moreover, efficient activation of the IRF-E by NDV is specifically inhibited by the protein kinase inhibitor, Staurosporin. Hence our results suggest the importance of IRF-1 synthesis and post-translational modification event(s), possibly phosphorylation for the efficient activation of IRF-Es, which are otherwise under negative regulation by IRF-2. Images PMID:1886766

  6. Synthesis, characterization and biocidal activities of Schiff base polychelates containing polyurethane links in the main chain

    NASA Astrophysics Data System (ADS)

    Hasnain, Sumaiya; Nishat, Nahid

    The concept of combining metallo-polymers with urethanes offers a versatile approach for the synthesis of new polymeric materials. Polyurethane containing transition metals was synthesized by the reaction of Schiff base metal complex with toluene 2,4 diisocyanate. The proposed structures were confirmed by elemental analysis, 1H NMR, 13C NMR and FT-IR. The geometry is determined by UV-Visible spectra and magnetic moment measurements, which reveals that the Mn(II), Co(II) and Ni(II) complexes have octahedral geometry while square planer geometry is reported for Cu(II) and tetrahedral for Zn(II) complex. The antimicrobial activities are determined using the agar well diffusion method with Staphylococcus aureus, Escherichia coli, Bacillus subtilis (bacteria), Aspergillus niger, Candida albicans and Aspergillus flavus (yeast). All the polymeric metal complexes show comparatively good biocidal activity, which is further enhanced after polymerization.

  7. A Systems Biology Approach to Link Nuclear Factor Kappa B Activation with Lethal Prostate Cancer

    DTIC Science & Technology

    2012-05-01

    progression of prostate cancer to a lethal disease . We aim to identify patients with lethal prostate cancer using a systems biology approach focused on...activation which are associated with lethal disease . (Months 1 to 18) Task 1A: Perform gene profiling of tumors and determine whether a set of genes and...panel to be assessed for correlation with lethal disease . (Month 1 to 18) Accomplishments: In the first 12 months of the grant we have (i

  8. Lung cancer: what are the links with oxidative stress, physical activity and nutrition.

    PubMed

    Filaire, Edith; Dupuis, Carmen; Galvaing, Géraud; Aubreton, Sylvie; Laurent, Hélène; Richard, Ruddy; Filaire, Marc

    2013-12-01

    Oxidative stress appears to play an essential role as a secondary messenger in the normal regulation of a variety of physiological processes, such as apoptosis, survival, and proliferative signaling pathways. Oxidative stress also plays important roles in the pathogenesis of many diseases, including aging, degenerative disease, and cancer. Among cancers, lung cancer is the leading cause of cancer in the Western world. Lung cancer is the commonest fatal cancer whose risk is dependent on the number of cigarettes smoked per day as well as the number of years smoking, some components of cigarette smoke inducing oxidative stress by transmitting or generating oxidative stress. It can be subdivided into two broad categories, small cell lung cancer and non-small-cell lung cancer, the latter is the most common type. Distinct measures of primary and secondary prevention have been investigated to reduce the risk of morbidity and mortality caused by lung cancer. Among them, it seems that physical activity and nutrition have some beneficial effects. However, physical activity can have different influences on carcinogenesis, depending on energy supply, strength and frequency of exercise loads as well as the degree of exercise-mediated oxidative stress. Micronutrient supplementation seems to have a positive impact in lung surgery, particularly as an antioxidant, even if the role of micronutrients in lung cancer remains controversial. The purpose of this review is to examine lung cancer in relation to oxidative stress, physical activity, and nutrition.

  9. Linking Nontraditional Physical Activity and Preterm Delivery in Urban African-American Women

    PubMed Central

    Sealy-Jefferson, Shawnita; Hegner, Kristy; Misra, Dawn P.

    2015-01-01

    Background Traditional risk factors for preterm delivery (PTD) do not account for the disparate rates among African-American women. Physical activity during pregnancy may protect women from PTD, but few studies exist in African Americans. Our objective was to examine the relationships between PTD and intensity and duration of leisure time physical activity (LTPA) as well as non-LTPA such as stair climbing and walking for a purpose during pregnancy. Methods Data were from a hybrid retrospective/prospective cohort study of urban low-income African-American women enrolled from 2001 to 2004 in the Baltimore PTD Study (n = 832). PTD was defined as birth before 37 completed weeks of gestation. Study participants reported physical activity during prenatal (n = 456) and post-partum (n = 376) interviews. Findings The rate of PTD was 16.7%. In unadjusted log-binomial regression models, we found no significant associations. However, in models adjusted for illicit drug use, locus of control, and a validated family resources scale, we found a significant decrease in prevalence of PTD for women who walked for a purpose more than 30 min/d (prevalence ratio, 0.64; 95% CI, 0.43–0.94), compared with women who walked less than or equal to 30 min/d. Conclusions These results suggest that walking for a purpose during pregnancy may confer protection against PTD among urban low-income African Americans. PMID:24981398

  10. Thymine DNA Glycosylase Is Essential for Active DNA Demethylation by Linked Deamination-Base Excision Repair

    PubMed Central

    Cortellino, Salvatore; Xu, Jinfei; Sannai, Mara; Moore, Robert; Caretti, Elena; Cigliano, Antonio; Le Coz, Madeleine; Devarajan, Karthik; Wessels, Andy; Soprano, Dianne; Abramowitz, Lara K.; Bartolomei, Marisa S.; Rambow, Florian; Bassi, Maria Rosaria; Bruno, Tiziana; Fanciulli, Maurizio; Renner, Catherine; Klein-Szanto, Andres J.; Matsumoto, Yoshihiro; Kobi, Dominique; Davidson, Irwin; Alberti, Christophe; Larue, Lionel; Bellacosa, Alfonso

    2011-01-01

    Summary DNA methylation is a major epigenetic mechanism for gene silencing. While methyltransferases mediate cytosine methylation, it is less clear how unmethylated regions in mammalian genomes are protected from de novo methylation and whether an active demethylating activity is involved. Here we show that either knockout or catalytic inactivation of the DNA repair enzyme Thymine DNA Glycosylase (TDG) leads to embryonic lethality in mice. TDG is necessary for recruiting p300 to retinoic acid (RA)-regulated promoters, protection of CpG islands from hypermethylation, and active demethylation of tissue-specific, developmentally- and hormonally-regulated promoters and enhancers. TDG interacts with the deaminase AID and the damage-response protein GADD45a. These findings highlight a dual role for TDG in promoting proper epigenetic states during development and suggest a two-step mechanism for DNA demethylation in mammals, whereby 5-methylcytosine and 5-hydroxymethylcytosine are first deaminated by AID to thymine and 5-hydroxymethyluracil, respectively, followed by TDG-mediated thymine and 5-hydroxymethyluracil excision repair. PMID:21722948

  11. Intersubject Variability in Fearful Face Processing: The Link Between Behavior and Neural Activation

    PubMed Central

    Doty, Tracy J.; Japee, Shruti; Ingvar, Martin; Ungerleider, Leslie G.

    2014-01-01

    Stimuli that signal threat show considerable variability in the extent to which they enhance behavior, even among healthy individuals. However, the neural underpinning of this behavioral variability is not well understood. By manipulating expectation of threat in an fMRI study of fearful vs. neutral face categorization, we uncovered a network of areas underlying variability in threat processing in healthy adults. We explicitly altered expectation by presenting face images at three different expectation levels: 80%, 50%, and 20%. Subjects were instructed to report as fast and as accurately as possible whether the face was fearful (signaled threat) or not. An uninformative cue preceded each face by 4 seconds (s). By taking the difference between response times (RT) to fearful compared to neutral faces, we quantified an overall fear RT bias (i.e. faster to fearful than neutral faces) for each subject. This bias correlated positively with late trial fMRI activation (8 s after the face) during unexpected fearful face trials in bilateral ventromedial prefrontal cortex, the left subgenual cingulate cortex, and the right caudate nucleus and correlated negatively with early trial fMRI activation (4 s after the cue) during expected neutral face trials in bilateral dorsal striatum and the right ventral striatum. These results demonstrate that the variability in threat processing among healthy adults is reflected not only in behavior but also in the magnitude of activation in medial prefrontal and striatal regions that appear to encode affective value. PMID:24841078

  12. Parabens inhibit human skin estrogen sulfotransferase activity: possible link to paraben estrogenic effects.

    PubMed

    Prusakiewicz, Jeffery J; Harville, Heather M; Zhang, Yanhua; Ackermann, Chrisita; Voorman, Richard L

    2007-04-11

    Parabens (p-hydroxybenzoate esters) are a group of widely used preservatives in topically applied cosmetic and pharmaceutical products. Parabens display weak associations with the estrogen receptors in vitro or in cell based models, but do exhibit estrogenic effects in animal models. It is our hypothesis that parabens exert their estrogenic effects, in part, by elevating levels of estrogens through inhibition of estrogen sulfotransferases (SULTs) in skin. We report here the results of a structure-activity-relationship of parabens as inhibitors of estrogen sulfation in human skin cytosolic fractions and normal human epidermal keratinocytes. Similar to reports of paraben estrogenicity and estrogen receptor affinity, the potency of SULT inhibition increased as the paraben ester chain length increased. Butylparaben was found to be the most potent of the parabens in skin cytosol, yielding an IC(50) value of 37+/-5 microM. Butylparaben blocked the skin cytosol sulfation of estradiol and estrone, but not the androgen dehydroepiandrosterone. The parabens were also tested as inhibitors of SULT activity in a cellular system, with normal human epidermal keratinocytes. The potency of butylparaben increased three-fold in these cells relative to the IC(50) value from skin cytosol. Overall, these results suggest chronic topical application of parabens may lead to prolonged estrogenic effects in skin as a result of inhibition of estrogen sulfotransferase activity. Accordingly, the skin anti-aging benefits of many topical cosmetics and pharmaceuticals could be derived, in part, from the estrogenicity of parabens.

  13. Prediction of Pneumococcal Conjugate Vaccine Effectiveness against Invasive Pneumococcal Disease Using Opsonophagocytic Activity and Antibody Concentrations Determined by Enzyme-Linked Immunosorbent Assay with 22F Adsorption ▿

    PubMed Central

    Schuerman, L.; Wysocki, J.; Tejedor, J. C.; Knuf, M.; Kim, K.-H.; Poolman, J.

    2011-01-01

    We compared the abilities of two serological readouts, antipolysaccharide IgG antibody concentrations and opsonophagocytic activity (OPA) titers, to predict the clinical effectiveness of the 7-valent pneumococcal conjugate vaccine (7vCRM) against invasive pneumococcal disease (IPD). We also assessed the accuracy of the previously established thresholds for GlaxoSmithKline's enzyme-linked immunosorbent assay with 22F adsorption (22F-ELISA) (≥0.2 μg/ml) and OPA assay (titer, ≥8) in predicting effectiveness. We showed that following a 3-dose 7vCRM primary vaccination, the serological response rates as determined using thresholds of ≥0.2 μg/ml IgG and an OPA titer of ≥8 corresponded well with overall effectiveness against IPD. In addition, the OPA assay seemed to better predict serotype-specific effectiveness than enzyme-linked immunoassay. Finally, when applied to post-dose-2 immune responses, both thresholds also corresponded well with the overall IPD effectiveness following a 2-dose 7vCRM primary vaccination. These results support the importance of the OPA assay in evaluating immune responses to pneumococcal conjugate vaccines. PMID:21994351

  14. High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR.

    PubMed

    Favoretto, Bruna C; Casabuono, Adriana A C; Portes-Junior, José A; Jacysyn, Jacqueline F; Couto, Alicia S; Faquim-Mauro, Eliana L

    2017-04-09

    Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. In addition, these N-linked glycoconjugates inhibited the DCs maturation induced by LPS. The binding and internalization of PI-Alexa were decreased on DCs previously incubated with mannan, anti-DC-SIGN and/or anti-MR antibodies. In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs.

  15. Downward Link of Solar Activity Variations Through Wave Driven Equatorial Oscillations (QBO and SAO)

    NASA Technical Reports Server (NTRS)

    Mengel, J. G.; Mayr, H. G.; Chan, K. L.; Porter, H. S.; Einaudi, Franco (Technical Monitor)

    2000-01-01

    Signatures of the 11-year solar activity/irradiance cycle are observed in the Quasi Biennial Oscillation (QBO) of the lower stratosphere. At these altitudes, the QBO is understood to be the result of "downward control" exerted by the wave mean flow interactions that drive the phenomenon. It is reasonable then to speculate that the QBO is a natural conduit to lower altitudes of solar activity variations in radiance (SAV). To test this hypothesis, we conducted experiments with a 2D version of our Numerical Spectral Model that incorporates Hines' Doppler Spread Parameterization for small-scale gravity waves (GW). To account for the SAV, we change the solar heating rate on a logarithmic scale from 0.1% at the surface to 1% at 50 kin to 10% at 100 km. With the same GW flux, we then conduct numerical experiments to evaluate the magnitude of the solar activity irradiance effect (SAE) on the zonal circulation at low latitudes. The numerical results obtained show that, under certain conditions, the SAE is significant in the zonal circulation and does extend to lower altitudes where the SAV is small. The differences in the wind velocities can be as large as 5 m/s at 20 kin. We carried out two numerical experiments with integrations over more than 20 years: 1) With the QBO period "tuned" to be 30 months, of academic interest but instructive, the seasonal cycle in the solar forcing [through the Semi-annual Oscillation (SAO)] acts as a strong pacemaker to produce a firm lock on the period and phase of the QBO. The SAE then shows up primarily as a distinct but relatively weak amplitude modulation. 2) With the QBO period between 30 and 34 (or less than 30, presumably) months, the seasonal phase lock is weak compared with (1). The SAV in the seasonal cycle then causes variations in the QBO period and phase, and this amplifies the SAE to produce relatively large variations in the wind field. We conclude that, under realistic conditions as in (2), the solar seasonal forcing, with

  16. Evidence that protons can be the active catalysts in Lewis acid mediated hetero-Michael addition reactions.

    PubMed

    Wabnitz, Tobias C; Yu, Jin-Quan; Spencer, Jonathan B

    2004-01-23

    The mechanism of Lewis acid catalysed hetero-Michael addition reactions of weakly basic nucleophiles to alpha,beta-unsaturated ketones was investigated. Protons, rather than metal ions, were identified as the active catalysts. Other mechanisms have been ruled out by analyses of side products and of stoichiometric enone-catalyst mixtures and by the use of radical inhibitors. No evidence for the involvement of pi-olefin-metal complexes or for carbonyl-metal-ion interactions was obtained. The reactions did not proceed in the presence of the non-coordinating base 2,6-di-tert-butylpyridine. An excellent correlation of catalytic activities with cation hydrolysis constants was obtained. Different reactivities of mono- and dicarbonyl substrates have been rationalised. A (1)H NMR probe for the assessment of proton generation was established and Lewis acids have been classified according to their propensity to hydrolyse in organic solvents. Brønsted acid-catalysed conjugate addition reactions of nitrogen, oxygen, sulfur and carbon nucleophiles are developed and implications for asymmetric Lewis acid catalysis are discussed.

  17. 34 CFR 403.71 - In what additional ways may funds be used under the State Programs and State Leadership Activities?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... State Programs and State Leadership Activities? 403.71 Section 403.71 Education Regulations of the... Secretary Assist Under the Basic Programs? State Programs and State Leadership Activities § 403.71 In what additional ways may funds be used under the State Programs and State Leadership Activities? In addition...

  18. An active triple-catalytic hybrid enzyme engineered by linking cyclo-oxygenase isoform-1 to prostacyclin synthase that can constantly biosynthesize prostacyclin, the vascular protector.

    PubMed

    Ruan, Ke-He; So, Shui-Ping; Cervantes, Vanessa; Wu, Hanjing; Wijaya, Cori; Jentzen, Rebecca R

    2008-12-01

    It remains a challenge to achieve the stable and long-term expression (in human cell lines) of a previously engineered hybrid enzyme [triple-catalytic (Trip-cat) enzyme-2; Ruan KH, Deng H & So SP (2006) Biochemistry45, 14003-14011], which links cyclo-oxygenase isoform-2 (COX-2) to prostacyclin (PGI(2)) synthase (PGIS) for the direct conversion of arachidonic acid into PGI(2) through the enzyme's Trip-cat functions. The stable upregulation of the biosynthesis of the vascular protector, PGI(2), in cells is an ideal model for the prevention and treatment of thromboxane A(2) (TXA(2))-mediated thrombosis and vasoconstriction, both of which cause stroke, myocardial infarction, and hypertension. Here, we report another case of engineering of the Trip-cat enzyme, in which human cyclo-oxygenase isoform-1, which has a different C-terminal sequence from COX-2, was linked to PGI(2) synthase and called Trip-cat enzyme-1. Transient expression of recombinant Trip-cat enzyme-1 in HEK293 cells led to 3-5-fold higher expression capacity and better PGI(2)-synthesizing activity as compared to that of the previously engineered Trip-cat enzyme-2. Furthermore, an HEK293 cell line that can stably express the active new Trip-cat enzyme-1 and constantly synthesize the bioactive PGI(2) was established by a screening approach. In addition, the stable HEK293 cell line, with constant production of PGI(2), revealed strong antiplatelet aggregation properties through its unique dual functions (increasing PGI(2) production while decreasing TXA(2) production) in TXA(2) synthase-rich plasma. This study has optimized engineering of the active Trip-cat enzyme, allowing it to become the first to stably upregulate PGI(2) biosynthesis in a human cell line, which provides a basis for developing a PGI(2)-producing therapeutic cell line for use against vascular diseases.

  19. Nutrient addition modifies phosphatase activities along an altitudinal gradient in a tropical montane forest in Southern Ecuador

    NASA Astrophysics Data System (ADS)

    Dietrich, Karla; Spoeri, Elena; Oelmann, Yvonne

    2016-02-01

    Atmospheric nutrient deposition and climate change are expected to endanger the diversity of tropical forest ecosystems. Nitrogen (N) deposition might influence nutrient fluxes beyond the N cycle by a concomitant increased demand for other nutritional elements such as phosphorus (P). Organisms might respond to the increased P demand by enhanced activity of enzymes involved in releasing inorganic P from organic matter (OM). Our aims were to assess the effect of i) climate shifts (approximated by an altitudinal gradient), and ii) nutrient addition (N, P, N+P) on phosphatase activity (PA) in organic layer and mineral soil of a tropical montane rainforest in Southern Ecuador. A nutrient manipulation experiment (NUMEX) was set up along an altitudinal gradient (1000, 2000, and 3000 m a.s.l.). We determined PA and inorganic and total P concentrations. PA at 1000 m was significantly lower (mean ± standard error: 48 ± 20 µmol p-NP g-1 dm h-1) as compared to 2000 m and 3000 m (119 ± 11 and 137 ± 19, respectively). One explanation might be that very rapid decomposition of OM at 1000 m results in very thin organic layers reducing the stabilization of enzymes and thus, resulting in leaching loss of enzymes under the humid tropical climate. We found no effect of N addition on PA neither in the organic layer nor in mineral soil, probably because of the low nutrient addition rates that showed ambiguous results so far on productivity measures as a proxy for P demand. In the organic layers of P and N+P treatments, we found decreased PA and increased concentrations of inorganic P. This indicates that the surplus of inorganic P reduced the biosynthesis of phosphatase enzymes. PA in megadiverse montane rainforests is likely to be unaffected by increased atmospheric N deposition but reduced upon atmospheric P deposition.

  20. Bulges and discs in the local Universe. Linking the galaxy structure to star formation activity

    NASA Astrophysics Data System (ADS)

    Morselli, L.; Popesso, P.; Erfanianfar, G.; Concas, A.

    2017-01-01

    We use a sample built on the SDSS DR7 catalogue and the bulge-disc decomposition of Simard et al. (2011, ApJS, 196, 11) to study how the bulge and disc components contribute to the parent galaxy's star formation activity, by determining its position in the star formation rate (SFR) - stellar mass (M⋆) plane at 0.02 < z < 0.1 and around the main sequence (MS) of star-forming galaxies. For this purpose, we use the bulge and disc colours as proxy for their SFRs, while the total galaxy SFR comes from Hα or D4000. We study the mean galaxy bulge-total mass ratio (B/T) as a function of the residual from the MS (ΔMS) and find that the B/T-ΔMS relation exhibits a parabola-like shape with the peak of the MS corresponding to the lowest B/Ts at any stellar mass. The lower and upper envelope of the MS are populated by galaxies with similar B/T, velocity dispersion and concentration (R90/R50) values. The mean values of such distributions indicate that the majority of the galaxies are characterised by classical bulges and not pseudo-bulges. Bulges above the MS are characterised by blue colours or, when red, by a high level of dust obscuration, thus indicating that in both cases they are actively star forming. When on the MS or below it, bulges are mostly red and dead. At stellar masses above 1010.5M⊙, bulges on the MS or in the green valley tend to be significantly redder than their counterparts in the quiescence region, despite similar levels of dust obscuration. This could be explained with different age or metallicity content, suggesting different evolutionary paths for bulges on the MS and green valley with respect to those in the quiescence region. The disc g-r colour anti-correlates at any mass with the distance from the MS, getting redder when approaching the MS lower envelope and the quiescence region. The anti-correlation flattens as a function of the stellar mass, likely due to a higher level of dust obscuration in massive SF galaxies. We conclude that the

  1. Passive and active microrheology for cross-linked F-actin networks in vitro.

    PubMed

    Lee, Hyungsuk; Ferrer, Jorge M; Nakamura, Fumihiko; Lang, Matthew J; Kamm, Roger D

    2010-04-01

    Actin filament (F-actin) is one of the dominant structural constituents in the cytoskeleton. Orchestrated by various actin-binding proteins (ABPs), F-actin is assembled into higher-order structures such as bundles and networks that provide mechanical support for the cell and play important roles in numerous cellular processes. Although mechanical properties of F-actin networks have been extensively studied, the underlying mechanisms for network elasticity are not fully understood, in part because different measurements probe different length and force scales. Here, we developed both passive and active microrheology techniques using optical tweezers to estimate the mechanical properties of F-actin networks at a length scale comparable to cells. For the passive approach we tracked the motion of a thermally fluctuating colloidal sphere to estimate the frequency-dependent complex shear modulus of the network. In the active approach, we used an optical trap to oscillate an embedded microsphere and monitored the response in order to obtain network viscoelasticity over a physiologically relevant force range. While both active and passive measurements exhibit similar results at low strain, the F-actin network subject to high strain exhibits non-linear behavior which is analogous to the strain-hardening observed in macroscale measurements. Using confocal and total internal reflection fluorescent microscopy, we also characterize the microstructure of reconstituted F-actin networks in terms of filament length, mesh size and degree of bundling. Finally, we propose a model of network connectivity by investigating the effect of filament length on the mechanical properties and structure.

  2. Modulating the synthetase activity of penicillin G acylase in organic media by addition of N-methylimidazole: using vinyl acetate as activated acyl donor.

    PubMed

    Liu, Bokai; Wu, Qi; Lv, Deshui; Lin, Xianfu

    2011-05-20

    This paper reported the modulation of enzyme activity by organic small molecule. The esterification activity of Penicillin G acylase (PGA) was improved more than 70-fold by the addition of 10% N-methylimidazole. Some control experiments have been designed to demonstrate the catalytic specificity of PGA. The structure and the amount of additive were optimized to improve the product yield. The influence of N-methylimidazole on the PGA conformation was investigated by FTIR and autodock simulation. Seven substrates were used to evaluate the effect of structure on the PGA-catalyzed transesterification. A series of products were successfully synthesized with the yield ranged from 56% to 84% and PGA showed specific recognition on the substrate with phenyl group in the presence of 10% N-methylimidazole.

  3. Recent advances in the link between physical activity, sedentary behavior, physical fitness, and colorectal cancer

    PubMed Central

    Namasivayam, Vikneswaran; Lim, Sam

    2017-01-01

    Physical inactivity is a well-established risk factor for colorectal cancer (CRC). Recent studies have characterized physical activity (PA), sedentary behavior, and cardiorespiratory fitness as distinct, interrelated constructs that influence the risk of CRC and related outcomes. PA levels required to confer protection against CRC may be higher than previously thought. Sedentary behavior, defined as time spent sitting, increases CRC risk independent of PA and may require novel interventions distinct from those targeting PA. Finally, cardiorespiratory fitness is inversely associated with CRC risk and mortality and may provide a potential tool for risk stratification and intervention. PMID:28344777

  4. Increased Motor Activity During REM Sleep Is Linked with Dopamine Function in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease

    PubMed Central

    Zoetmulder, Marielle; Nikolic, Miki; Biernat, Heidi; Korbo, Lise; Friberg, Lars; Jennum, Poul

    2016-01-01

    Study Objectives: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by impaired motor inhibition during REM sleep, and dream-enacting behavior. RBD is especially associated with α-synucleinopathies, such as Parkinson disease (PD). Follow-up studies have shown that patients with idiopathic RBD (iRBD) have an increased risk of developing an α-synucleinopathy in later life. Although abundant studies have shown that degeneration of the nigrostriatal dopaminergic system is associated with daytime motor function in Parkinson disease, only few studies have investigated the relation between this system and electromyographic (EMG) activity during sleep. The objective of this study was to investigate the relationship between the nigrostriatal dopamine system and muscle activity during sleep in iRBD and PD. Methods: 10 iRBD patients, 10 PD patients with PD, 10 PD patients without RBD, and 10 healthy controls were included and assessed with (123)I-N-omega-fluoropropyl-2-beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane ((123)I-FP-CIT) Single-photon emission computed tomography (SPECT) scanning (123I-FP-CIT SPECT), neurological examination, and polysomnography. Results: iRBD patients and PD patients with RBD had increased EMG-activity compared to healthy controls. 123I-FP-CIT uptake in the putamen-region was highest in controls, followed by iRBD patients, and lowest in PD patients. In iRBD patients, EMG-activity in the mentalis muscle was correlated to 123I-FP-CIT uptake in the putamen. In PD patients, EMG-activity was correlated to anti-Parkinson medication. Conclusions: Our results support the hypothesis that increased EMG-activity during REM sleep is at least partly linked to the nigrostriatal dopamine system in iRBD, and with dopamine function in PD. Citation: Zoetmulder M, Nikolic M, Biernat H, Korbo L, Friberg L, Jennum P. Increased motor activity during rem sleep is linked with dopamine function in idiopathic REM sleep behavior

  5. Zoledronic acid inhibits aromatase activity and phosphorylation: potential mechanism for additive zoledronic acid and letrozole drug interaction.

    PubMed

    Schech, Amanda J; Nemieboka, Brandon E; Brodie, Angela H

    2012-11-01

    Zoledronic acid (ZA), a bisphosphonate originally indicated for use in osteoporosis, has been reported to exert a direct effect on breast cancer cells, although the mechanism of this effect is currently unknown. Data from the ABCSG-12 and ZO-FAST clinical trials suggest that treatment with the combination of ZA and aromatase inhibitors (AI) result in increased disease free survival in breast cancer patients over AI alone. To determine whether the mechanism of this combination involved inhibition of aromatase, AC-1 cells (MCF-7 human breast cancer cells transfected with an aromatase construct) were treated simultaneously with combinations of ZA and AI letrozole. This combination significantly increased inhibition of aromatase activity of AC-1 cells when compared to letrozole alone. Treatment of 1 nM letrozole in combination with 1 μM or 10 μM ZA resulted in an additive drug interaction on inhibition of cell viability, as measured by MTT assay. Treatment with ZA was found to inhibit phosphorylation of aromatase on serine residues. Zoledronic acid was also shown to be more effective in inhibiting cell viability in aromatase transfected AC-1 cells when compared to inhibition of cell viability observed in non-transfected MCF-7. Estradiol was able to partially rescue the effect of 1 μM and 10 μM ZA on cell viability following treatment for 72 h, as shown by a shift to the right in the estradiol dose-response curve. In conclusion, these results indicate that the combination of ZA and letrozole results in an additive inhibition of cell viability. Furthermore, ZA alone can inhibit aromatase activity through inhibition of serine phosphorylation events important for aromatase enzymatic activity and contributes to inhibition of cell viability.

  6. EDTA addition enhances bacterial respiration activities and hydrocarbon degradation in bioaugmented and non-bioaugmented oil-contaminated desert soils.

    PubMed

    Al Kharusi, Samiha; Abed, Raeid M M; Dobretsov, Sergey

    2016-03-01

    The low number and activity of hydrocarbon-degrading bacteria and the low solubility and availability of hydrocarbons hamper bioremediation of oil-contaminated soils in arid deserts, thus bioremediation treatments that circumvent these limitations are required. We tested the effect of Ethylenediaminetetraacetic acid (EDTA) addition, at different concentrations (i.e. 0.1, 1 and 10 mM), on bacterial respiration and biodegradation of Arabian light oil in bioaugmented (i.e. with the addition of exogenous alkane-degrading consortium) and non-bioaugmented oil-contaminated desert soils. Post-treatment shifts in the soils' bacterial community structure were monitored using MiSeq sequencing. Bacterial respiration, indicated by the amount of evolved CO2, was highest at 10 mM EDTA in bioaugmented and non-bioaugmented soils, reaching an amount of 2.2 ± 0.08 and 1.6 ± 0.02 mg-CO2 g(-1) after 14 days of incubation, respectively. GC-MS revealed that 91.5% of the C14-C30 alkanes were degraded after 42 days when 10 mM EDTA and the bacterial consortium were added together. MiSeq sequencing showed that 78-91% of retrieved sequences in the original soil belonged to Deinococci, Alphaproteobacteria, Gammaproteobacteia and Bacilli. The same bacterial classes were detected in the 10 mM EDTA-treated soils, however with slight differences in their relative abundances. In the bioaugmented soils, only Alcanivorax sp. MH3 and Parvibaculum sp. MH21 from the exogenous bacterial consortium could survive until the end of the experiment. We conclude that the addition of EDTA at appropriate concentrations could facilitate biodegradation processes by increasing hydrocarbon availability to microbes. The addition of exogenous oil-degrading bacteria along with EDTA could serve as an ideal solution for the decontamination of oil-contaminated desert soils.

  7. Methylmalonate Induces Inflammatory and Apoptotic Potential: A Link to Glial Activation and Neurological Dysfunction.

    PubMed

    Gabbi, Patricia; Ribeiro, Leandro Rodrigo; Jessié Martins, Gutierres; Cardoso, Alexandra Seide; Haupental, Fernanda; Rodrigues, Fernanda Silva; Machado, Alencar Kolinski; Sperotto Brum, Juliana; Medeiros Frescura Duarte, M M; Schetinger, Maria Rosa Chitolina; da Cruz, Ivana Beatrice Mânica; Flávia Furian, Ana; Oliveira, Mauro Schneider; Dos Santos, Adair Roberto Soares; Royes, Luiz Fernando Freire; Fighera, Michele Rechia; de Freitas, Mayara Lutchemeyer

    2017-03-01

    Methylmalonic acid (MMA) accumulates in tissues in methylmalonic acidemia, a heterogeneous group of inherited childhood diseases characterized by neurological dysfunction, oxidative stress and neuroinflammation; it is associated with degeneration of striatal neurons and cerebral cortical atrophy. It is presently unknown, however, whether transient exposure to MMA in the neonatal period is sufficient to trigger inflammatory and apoptotic processes that lead to brain structural damage. Here, newborn mice were given a single intracerebroventricular dose of MMA at 12 hours after birth. Maze testing of 21- and 40-day-old mice showed that MMA-injected animals exhibited deficit in the working memory test but not in the reference test. MMA-injected mice showed increased levels of the reactive oxygen species marker 2',7'-dichlorofluorescein diacetate, tumor necrosis factor, interleukin-1β, caspases 1, 3, and 8, and increased acetylcholinesterase activity in the cortex, hippocampus and striatum. This was associated with increased astrocyte and microglial immunoreactivity in all brain regions. These findings suggest that transient exposure to MMA may alter the redox state and cause neuroinflammatory/apoptotic processes and glial activation during critical periods of brain development. Similar processes may underlie brain dysfunction and cognitive impairment in patients with methylmalonic acidemia.

  8. Locked and loading megathrust linked to active subduction beneath the Indo-Burman Ranges

    NASA Astrophysics Data System (ADS)

    Steckler, Michael S.; Mondal, Dhiman Ranjan; Akhter, Syed Humayun; Seeber, Leonardo; Feng, Lujia; Gale, Jonathan; Hill, Emma M.; Howe, Michael

    2016-08-01

    The Indo-Burman mountain ranges mark the boundary between the Indian and Eurasian plates, north of the Sumatra-Andaman subduction zone. Whether subduction still occurs along this subaerial section of the plate boundary, with 46 mm yr-1 of highly oblique motion, is contentious. About 21 mm yr-1 of shear motion is taken up along the Sagaing Fault, on the eastern margin of the deformation zone. It has been suggested that the remainder of the relative motion is taken up largely or entirely by horizontal strike-slip faulting and that subduction has stopped. Here we present GPS measurements of plate motions in Bangladesh, combined with measurements from Myanmar and northeast India, taking advantage of a more than 300 km subaerial accretionary prism spanning the Indo-Burman Ranges to the Ganges-Brahmaputra Delta. They reveal 13-17 mm yr-1 of plate convergence on an active, shallowly dipping and locked megathrust fault. Most of the strike-slip motion occurs on a few steep faults, consistent with patterns of strain partitioning in subduction zones. Our results strongly suggest that subduction in this region is active, despite the highly oblique plate motion and thick sediments. We suggest that the presence of a locked megathrust plate boundary represents an underappreciated hazard in one of the most densely populated regions of the world.

  9. Daily Parental Knowledge of Youth Activities Is Linked to Youth Physical Symptoms and HPA functioning

    PubMed Central

    Lippold, Melissa A.; Davis, Kelly D.; McHale, Susan M.; Almeida, David M.

    2015-01-01

    Considerable evidence documents linkages between parental knowledge of youth activities and youth risky behavior. We extended this research to determine whether parental knowledge was associated with youth physical health, including reports of physical symptoms (e.g., headaches, stomachaches) and a biomarker of hypothalamic pituitary adrenocortical (HPA) axis functioning (i.e., salivary cortisol levels). Participants were children of employees in the Information Technology division of a Fortune 500 company (N = 132, Mean Age Youth = 13.39 years, 55% female) who participated in a daily diary study. Data were collected via telephone calls on eight consecutive evenings. On four study days, cortisol samples were collected at 4 time points (waking, 30 min after waking, before dinner, bedtime). Multi-level models revealed that, at the between-person level, youth whose parents had higher average knowledge about their activities, exhibited lower bedtime cortisol levels. Furthermore, at the within-person level, on days when parents displayed more knowledge than usual (relative to their own eight-day average), youth had lower before-dinner cortisol than usual. Linkages between average parental knowledge and physical health symptoms were moderated by youth age: Younger but not older adolescents whose parents were more knowledgeable had fewer physical health symptoms, on average. A next step is to identify the processes that underlie these associations. PMID:26751757

  10. Linking storm surge activity and circulation variability along the Spanish coast through a synoptic pattern classification

    NASA Astrophysics Data System (ADS)

    Rasilla Álvarez, Domingo; Garcia Codrón, Juan Carlos

    2010-05-01

    The potentially negative consequences resulting from the estimations of global sea level rising along the current century are a matter of serious concern in many coastal areas worldwide. Most of the negative consequences of the sea level variability, such as flooding or erosion, are linked to episodic events of strong atmospheric forcing represented by deep atmospheric disturbances, especially if they combine with extreme astronomical high tides. Moreover, the interaction between the prevailing flows during such events and the actual orientation of the coast line might accelerate or mitigate such impacts. This contribution analyses sea surge variations measured at five tide-gauge stations located around the Iberian Peninsula and their relationships with regional scale circulation patterns with local-scale winds. Its aim is to improve the knowledge of surge related-coastal-risks by analysing the relationship between surges and their atmospheric forcing factors at different spatial scales. The oceanographic data set consists of hourly data from 5 tide gauge stations (Santander, Vigo, Bonanza, Málaga, Valencia and Barcelona) disseminated along the Spanish coastline, provided by Puertos del Estado. To explore the atmospheric mechanisms responsible for the sign and magnitude of sea surges, a regional Eulerian approach (a synoptic typing) were combined with a larger-scale Lagrangian method, based on the analysis of storm-tracks over the Atlantic and local information (synop reports) obtained from the closest meteorological stations to the tide gauges. The synoptic catalogue was obtained following a procedure that combines Principal Component Analysis (PCA) for reduction purposes and clustering (Ward plus K-means) to define the circulation types. Sea level pressure, surface 10m U and V wind components gridded data were obtained from NCEP Reanalysis, while storm tracks and cyclone statistics were extracted from the CDC Map Room Climate Products Storm Track Data (http

  11. DNA-directed alkylating agents. 3. Structure-activity relationships for acridine-linked aniline mustards: consequences of varying the length of the linker chain.

    PubMed

    Valu, K K; Gourdie, T A; Boritzki, T J; Gravatt, G L; Baguley, B C; Wilson, W R; Wakelin, L P; Woodgate, P D; Denny, W A

    1990-11-01

    Four series of acridine-linked aniline mustards have been prepared and evaluated for in vitro cytotoxicity, in vivo antitumor activity, and DNA cross-linking ability. The anilines were attached to the DNA-intercalating acridine chromophores by link groups (-O-, -CH2-, -S-, and -SO2-) of widely varying electronic properties, providing four series of widely differing mustard reactivity where the alkyl chain linking the acridine and mustard moieties was varied from two to five carbons. Relationships were sought between chain length and biological properties. Within each series, increasing the chain length did not alter the reactivity of the alkylating moiety but did appear to position it differently on the DNA, since cross-linking ability (measured by agarose gel assay) altered with chain length, being maximal with the C4 analogue. The in vivo antitumor activities of the compounds depended to some extent on the reactivity of the mustard, with the least reactive SO2 compounds being inactive. However, DNA-targeting did appear to allow the use of less reactive mustards, since the S-linked acridine mustards showed significant activity whereas the parent S-mustard did not. Within each active series, the most active compound was the C4 homologue, suggesting some relationship between activity and extent of DNA alkylation.

  12. Periodic Analysis of Solar Activity and its Link with the Arctic Oscillation Phenomenon

    NASA Astrophysics Data System (ADS)

    Qu, Weizheng; Li, Yanfang; Li, Chun; Du, Ling; Huang, Fei

    2014-12-01

    Based on spectrum analysis, we provide the arithmetic expressions of the quasi 11 yr cycle, 110 yr century cycle of relative sunspot numbers, and quasi 22 yr cycle of solar magnetic field polarity. Based on a comparative analysis of the monthly average geopotential height, geopotential height anomaly, and temperature anomaly of the northern hemisphere at locations with an air pressure of 500 hPa during the positive and negative phases of AO (Arctic Oscillation), one can see that the abnormal warming period in the Arctic region corresponds to the negative phase of AO, while the anomalous cold period corresponds to its positive phase. This shows that the abnormal change in the Arctic region is an important factor in determining the anomalies of AO. In accordance with the analysis performed using the successive filtering method, one can see that the AO phenomenon occurring in January shows a clear quasi 88 yr century cycle and quasi 22 yr decadal cycle, which are closely related to solar activities. The results of our comparative analysis show that there is a close inverse relationship between the solar activities (especially the solar magnetic field index changes) and the changes in the 22 yr cycle of the AO occurring in January, and that the two trends are basically opposite of each other. That is to say, in most cases after the solar magnetic index MI rises from the lowest value, the solar magnetic field turns from north to south, and the high-energy particle flow entering the Earth's magnetosphere increases to heat the polar atmosphere, thus causing the AO to drop from the highest value; after the solar magnetic index MI drops from the highest value, the solar magnetic field turns from south to north, and the solar high-energy particle flow passes through the top of the Earth's magnetosphere rather than entering it to heat the polar atmosphere. Thus the polar temperature drops, causing the AO to rise from the lowest value. In summary, the variance contribution

  13. Periodic analysis of solar activity and its link with the Arctic oscillation phenomenon

    SciTech Connect

    Qu, Weizheng; Li, Chun; Du, Ling; Huang, Fei; Li, Yanfang

    2014-12-01

    Based on spectrum analysis, we provide the arithmetic expressions of the quasi 11 yr cycle, 110 yr century cycle of relative sunspot numbers, and quasi 22 yr cycle of solar magnetic field polarity. Based on a comparative analysis of the monthly average geopotential height, geopotential height anomaly, and temperature anomaly of the northern hemisphere at locations with an air pressure of 500 HPa during the positive and negative phases of AO (Arctic Oscillation), one can see that the abnormal warming period in the Arctic region corresponds to the negative phase of AO, while the anomalous cold period corresponds to its positive phase. This shows that the abnormal change in the Arctic region is an important factor in determining the anomalies of AO. In accordance with the analysis performed using the successive filtering method, one can see that the AO phenomenon occurring in January shows a clear quasi 88 yr century cycle and quasi 22 yr decadal cycle, which are closely related to solar activities. The results of our comparative analysis show that there is a close inverse relationship between the solar activities (especially the solar magnetic field index changes) and the changes in the 22 yr cycle of the AO occurring in January, and that the two trends are basically opposite of each other. That is to say, in most cases after the solar magnetic index MI rises from the lowest value, the solar magnetic field turns from north to south, and the high-energy particle flow entering the Earth's magnetosphere increases to heat the polar atmosphere, thus causing the AO to drop from the highest value; after the solar magnetic index MI drops from the highest value, the solar magnetic field turns from south to north, and the solar high-energy particle flow passes through the top of the Earth's magnetosphere rather than entering it to heat the polar atmosphere. Thus the polar temperature drops, causing the AO to rise from the lowest value. In summary, the variance contribution

  14. A statistical method linking geological and historical eruption time series for volcanic hazard estimations: Applications to active polygenetic volcanoes

    NASA Astrophysics Data System (ADS)

    Mendoza-Rosas, Ana Teresa; De la Cruz-Reyna, Servando

    2008-09-01

    The probabilistic analysis of volcanic eruption time series is an essential step for the assessment of volcanic hazard and risk. Such series describe complex processes involving different types of eruptions over different time scales. A statistical method linking geological and historical eruption time series is proposed for calculating the probabilities of future eruptions. The first step of the analysis is to characterize the eruptions by their magnitudes. As is the case in most natural phenomena, lower magnitude events are more frequent, and the behavior of the eruption series may be biased by such events. On the other hand, eruptive series are commonly studied using conventional statistics and treated as homogeneous Poisson processes. However, time-dependent series, or sequences including rare or extreme events, represented by very few data of large eruptions require special methods of analysis, such as the extreme-value theory applied to non-homogeneous Poisson processes. Here we propose a general methodology for analyzing such processes attempting to obtain better estimates of the volcanic hazard. This is done in three steps: Firstly, the historical eruptive series is complemented with the available geological eruption data. The linking of these series is done assuming an inverse relationship between the eruption magnitudes and the occurrence rate of each magnitude class. Secondly, we perform a Weibull analysis of the distribution of repose time between successive eruptions. Thirdly, the linked eruption series are analyzed as a non-homogeneous Poisson process with a generalized Pareto distribution as intensity function. As an application, the method is tested on the eruption series of five active polygenetic Mexican volcanoes: Colima, Citlaltépetl, Nevado de Toluca, Popocatépetl and El Chichón, to obtain hazard estimates.

  15. Bifunctional Molecular Photoswitches Based on Overcrowded Alkenes for Dynamic Control of Catalytic Activity in Michael Addition Reactions.

    PubMed

    Pizzolato, Stefano F; Collins, Beatrice S L; van Leeuwen, Thomas; Feringa, Ben L

    2016-11-23

    The emerging field of artificial photoswitchable catalysis has recently shown striking examples of functional light-responsive systems allowing for dynamic control of activity and selectivity in organocatalysis and metal-catalysed transformations. While our group has already disclosed systems featuring first generation molecular motors as the switchable central core, a design based on second generation molecular motors is lacking. Here, the syntheses of two bifunctionalised molecular switches based on a photoresponsive tetrasubstituted alkene core are reported. They feature a thiourea substituent as hydrogen-donor moiety in the upper half and a basic dimethylamine group in the lower half. This combination of functional groups offers the possibility for application of these molecules in photoswitchable catalytic processes. The light-responsive central cores were synthesized by a Barton-Kellogg coupling of the prefunctionalized upper and lower halves. Derivatization using Buchwald-Hartwig amination and subsequent introduction of the thiourea substituent afforded the target compounds. Control of catalytic activity in the Michael addition reaction between (E)-3-bromo-β-nitrostyrene and 2,4-pentanedione is achieved upon irradiation of stable-(E) and stable-(Z) isomers of the bifunctional catalyst 1. Both isomers display a decrease in catalytic activity upon irradiation to the metastable state, providing systems with the potential to be applied as ON/OFF catalytic photoswitches.

  16. Antibacterial and antifungal activities of Otanthus maritimus (L.) Hoffmanns. & Link essential oil from Sicily.

    PubMed

    Basile, Adriana; Rigano, Daniela; Sorbo, Sergio; Conte, Barbara; Rosselli, Sergio; Bruno, Maurizio; Senatore, Felice

    2013-01-01

    The chemical composition of the essential oil obtained from the flowers of Otanthus maritimus L., a perennial plant growing wild in maritime sands in the Mediterranean region, was investigated by GC and GC-MS analyses. Totally 66 were identified. The oil was dominated by the high content of monoterpene compounds, especially oxygenated monoterpenes which accounted for 73.1%. The most abundant components were yomogi alcohol (20.8%), camphor (15.8%), artemisyl acetate (15.3%) and artemisia alcohol (13.7%). The oil was tested against two Gram (+) and six Gram (-) bacterial strains, both American Type Culture Collection standard strains and clinically isolated (CI), one potentially pathogenic yeast (Candida albicans CI) and two filamentous phytopathogenic fungi (Botrytis cinerea and Rhizoctonia solani). The results show that the oil from O. maritimus exerts strong antibacterial and antifungal activities.

  17. RADIO-LOUD ACTIVE GALACTIC NUCLEUS: IS THERE A LINK BETWEEN LUMINOSITY AND CLUSTER ENVIRONMENT?

    SciTech Connect

    Ineson, J.; Croston, J. H.; Hardcastle, M. J.; Jarvis, M.; Kraft, R. P.; Evans, D. A.

    2013-06-20

    We present here the first results from the Chandra ERA (Environments of Radio-loud AGN) Large Project, characterizing the cluster environments of a sample of 26 radio-loud active galactic nuclei (AGNs) at z {approx} 0.5 that covers three decades of radio luminosity. This is the first systematic X-ray environmental study at a single epoch, and has allowed us to examine the relationship between radio luminosity and cluster environment without the problems of Malmquist bias. We have found a weak correlation between radio luminosity and host cluster X-ray luminosity, as well as tentative evidence that this correlation is driven by the subpopulation of low-excitation radio galaxies, with high-excitation radio galaxies showing no significant correlation. The considerable scatter in the environments may be indicative of complex relationships not currently included in feedback models.

  18. An infrared jet in Centaurus A - A link to the extranuclear activity in distant radio galaxies?

    NASA Technical Reports Server (NTRS)

    Joy, Marshall; Harvey, P. M.; Tollestrup, E. V.; Sellgren, K.; Mcgregor, P. J.

    1991-01-01

    High-resolution NIR images of the visually obscured central region of Centaurus A (NGC 5128) were obtained with the University of Texas array camera on the AAT in June 1988, in order to investigate the effect of the active nucleus on the surrounding galaxy. The J (1.25 micron), H (1.65 micron), and K (2.2 micron) images of the central 40 arcsec of the galaxy revealed an emission feature extending about 10 arcsec northeast of the nucleus at the same position angle as the X-ray and radio jets. This jet is most prominent at the 1.25 micron wavelength, where its brightness was comparable to that of the nucleus. The observed properties of the 'infrared jet' were found to be similar to those seen in distant radio sources.

  19. Mid-Holocene Hemlock Decline in Eastern North America Linked with Phytophagous Insect Activity

    NASA Astrophysics Data System (ADS)

    Bhiry, Najat; Filion, Louise

    1996-05-01

    Macrofossil evidence indicates that the mid-Holocene hemlock [ Tsuga canadensisL. (Carr.)] decline that occurred over a wide area in eastern North America was associated with phytophagous insect activity. In situhemlock macrofossils and insect remains found in a paludified dunefield at the northern limit of hemlock testify that two defoliation events occurred at 4910 ± 90 and 4200 ± 100 yr B.P., respectively. The sharp coincidence of remains from hemlock needles with chewing damage typical of hemlock looper feeding, head capsules from the hemlock looper ( Lambdina fiscellaria) and the spruce budworm ( Choristoneura fumiferana), absence of hemlock fruiting remains, and tree-ring anomalies in fossil hemlocks that died prematurely (<165 yr) suggest that defoliation affected hemlock reproductive capacity and pollen productivity, or more likely caused mass mortality. Our findings indicate that defoliation can affect ecosystems for centuries, especially when long-lived tree species are involved.

  20. Genome-wide analysis links emerin to neuromuscular junction activity in Caenorhabditis elegans

    PubMed Central

    2014-01-01

    Background Laminopathies are diseases characterized by defects in nuclear envelope structure. A well-known example is Emery-Dreifuss muscular dystrophy, which is caused by mutations in the human lamin A/C and emerin genes. While most nuclear envelope proteins are ubiquitously expressed, laminopathies often affect only a subset of tissues. The molecular mechanisms underlying these tissue-specific manifestations remain elusive. We hypothesize that different functional subclasses of genes might be differentially affected by defects in specific nuclear envelope components. Results Here we determine genome-wide DNA association profiles of two nuclear envelope components, lamin/LMN-1 and emerin/EMR-1 in adult Caenorhabditis elegans. Although both proteins bind to transcriptionally inactive regions of the genome, EMR-1 is enriched at genes involved in muscle and neuronal function. Deletion of either EMR-1 or LEM-2, another integral envelope protein, causes local changes in nuclear architecture as evidenced by altered association between DNA and LMN-1. Transcriptome analyses reveal that EMR-1 and LEM-2 are associated with gene repression, particularly of genes implicated in muscle and nervous system function. We demonstrate that emr-1, but not lem-2, mutants are sensitive to the cholinesterase inhibitor aldicarb, indicating altered activity at neuromuscular junctions. Conclusions We identify a class of elements that bind EMR-1 but do not associate with LMN-1, and these are enriched for muscle and neuronal genes. Our data support a redundant function of EMR-1 and LEM-2 in chromatin anchoring to the nuclear envelope and gene repression. We demonstrate a specific role of EMR-1 in neuromuscular junction activity that may contribute to Emery-Dreifuss muscular dystrophy in humans. PMID:24490688

  1. Link between plasminogen activator inhibitor-1 and cardiovascular risk in chronic hepatitis C after viral clearance.

    PubMed

    Chang, Ming-Ling; Lin, Yu-Sheng; Pao, Li-Heng; Huang, Hsin-Chih; Chiu, Cheng-Tang

    2017-02-13

    The pathophysiological implications of plasminogen activator inhibitor-1 (PAI-1) in HCV infection remain obscure. This prospective study evaluated 669 HCV patients, of whom 536 had completed a course of anti-HCV therapy and had pre-, peri- and post-therapy measurements of various profiles, including PAI-1 levels. Multivariate analysis demonstrated, before anti-HCV-therapy, platelet count and PAI-1-rs1799889 genotype were associated with PAI-1 levels. Among patients with a sustained virological response (SVR, n = 445), platelet count was associated with PAI-1 level at 24 weeks post-therapy. GEE analysis showed that PAI-1-rs-1799889 and interferon-λ3-rs12979860 genotypes affected PAI-1 levels early and late in therapy, respectively. At 24 weeks post-therapy, higher lipid, brain natriuretic peptide, homocysteine and PAI-1 levels and PAI-1 activity were noted only in SVR patients compared with pre-therapy levels. Within 24 weeks post-therapy, 2.2% of the SVR (mean age: 57.8 yr; 8 smoking males; the 2 females had pre-therapy hypercholesteremia or cardiovascular family history of disease) and 0% of the non-SVR patients experienced a new cardiovascular event. Platelet counts consistently correlated with PAI-1 levels regardless of HCV infection. PAI-1-rs-1799889 and interferon-λ3-rs12979860 genotypes mainly affected PAI-1 levels longitudinally. Within 24 weeks post-anti-HCV therapy, the SVR patients showed increasing PAI-1 levels with accelerating cardiovascular risk, especially the vulnerable cases.

  2. Linking Microbial Enzymatic Activities and Functional Diversity of Soil around Earthworm Burrows and Casts.

    PubMed

    Lipiec, Jerzy; Frąc, Magdalena; Brzezińska, Małgorzata; Turski, Marcin; Oszust, Karolina

    2016-01-01

    The aim of this work was to evaluate the effect of earthworms (Lumbricidae) on the enzymatic activity and microbial functional diversity in the burrow system [burrow wall (BW) 0-3 mm, transitional zone (TZ) 3-7 mm, bulk soil (BS) > 20 mm from the BW] and cast aggregates of a loess soil under a pear orchard. The dehydrogenase, β-glucosidase, protease, alkaline phosphomonoesterase, and acid phosphomonoesterase enzymes were assessed using standard methods. The functional diversity (catabolic potential) was assessed using the Average Well Color Development and Richness Index following the community level physiological profiling from Biolog Eco Plates. All measurements were done using soil from each compartment immediately after in situ sampling in spring. The enzymatic activites including dehydrogenase, protease, β-glucosidase and alkaline phosphomonoesterase were appreciably greater in the BW or casts than in BS and TZ. Conversely, acid phosphomonoesterase had the largest value in the BS. Average Well Color Development in both the TZ and the BS (0.98-0.94 A590 nm) were more than eight times higher than in the BWs and casts. The lowest richness index in the BS (15 utilized substrates) increased by 86-113% in all the other compartments. The PC1 in principal component analysis mainly differentiated the BWs and the TZ. Utilization of all substrate categories was the lowest in the BS. The PC2 differentiated the casts from the other compartments. The enhanced activity of a majority of the enzymes and increased microbial functional diversity in most earthworm-influenced compartments make the soils less vulnerable to degradation and thus increases the stability of ecologically relevant processes in the orchard ecosystem.

  3. A Link between ORC-Origin Binding Mechanisms and Origin Activation Time Revealed in Budding Yeast

    PubMed Central

    Hoggard, Timothy; Shor, Erika; Müller, Carolin A.; Nieduszynski, Conrad A.; Fox, Catherine A.

    2013-01-01

    Eukaryotic DNA replication origins are selected in G1-phase when the origin recognition complex (ORC) binds chromosomal positions and triggers molecular events culminating in the initiation of DNA replication (a.k.a. origin firing) during S-phase. Each chromosome uses multiple origins for its duplication, and each origin fires at a characteristic time during S-phase, creating a cell-type specific genome replication pattern relevant to differentiation and genome stability. It is unclear whether ORC-origin interactions are relevant to origin activation time. We applied a novel genome-wide strategy to classify origins in the model eukaryote Saccharomyces cerevisiae based on the types of molecular interactions used for ORC-origin binding. Specifically, origins were classified as DNA-dependent when the strength of ORC-origin binding in vivo could be explained by the affinity of ORC for origin DNA in vitro, and, conversely, as ‘chromatin-dependent’ when the ORC-DNA interaction in vitro was insufficient to explain the strength of ORC-origin binding in vivo. These two origin classes differed in terms of nucleosome architecture and dependence on origin-flanking sequences in plasmid replication assays, consistent with local features of chromatin promoting ORC binding at ‘chromatin-dependent’ origins. Finally, the ‘chromatin-dependent’ class was enriched for origins that fire early in S-phase, while the DNA-dependent class was enriched for later firing origins. Conversely, the latest firing origins showed a positive association with the ORC-origin DNA paradigm for normal levels of ORC binding, whereas the earliest firing origins did not. These data reveal a novel association between ORC-origin binding mechanisms and the regulation of origin activation time. PMID:24068963

  4. Linking Microbial Enzymatic Activities and Functional Diversity of Soil around Earthworm Burrows and Casts

    PubMed Central

    Lipiec, Jerzy; Frąc, Magdalena; Brzezińska, Małgorzata; Turski, Marcin; Oszust, Karolina

    2016-01-01

    The aim of this work was to evaluate the effect of earthworms (Lumbricidae) on the enzymatic activity and microbial functional diversity in the burrow system [burrow wall (BW) 0–3 mm, transitional zone (TZ) 3–7 mm, bulk soil (BS) > 20 mm from the BW] and cast aggregates of a loess soil under a pear orchard. The dehydrogenase, β-glucosidase, protease, alkaline phosphomonoesterase, and acid phosphomonoesterase enzymes were assessed using standard methods. The functional diversity (catabolic potential) was assessed using the Average Well Color Development and Richness Index following the community level physiological profiling from Biolog Eco Plates. All measurements were done using soil from each compartment immediately after in situ sampling in spring. The enzymatic activites including dehydrogenase, protease, β-glucosidase and alkaline phosphomonoesterase were appreciably greater in the BW or casts than in BS and TZ. Conversely, acid phosphomonoesterase had the largest value in the BS. Average Well Color Development in both the TZ and the BS (0.98–0.94 A590 nm) were more than eight times higher than in the BWs and casts. The lowest richness index in the BS (15 utilized substrates) increased by 86–113% in all the other compartments. The PC1 in principal component analysis mainly differentiated the BWs and the TZ. Utilization of all substrate categories was the lowest in the BS. The PC2 differentiated the casts from the other compartments. The enhanced activity of a majority of the enzymes and increased microbial functional diversity in most earthworm-influenced compartments make the soils less vulnerable to degradation and thus increases the stability of ecologically relevant processes in the orchard ecosystem. PMID:27625645

  5. The Link Between Physical Activity and Cognitive Dysfunction in Alzheimer Disease.

    PubMed

    Phillips, Cristy; Baktir, Mehmet Akif; Das, Devsmita; Lin, Bill; Salehi, Ahmad

    2015-07-01

    Alzheimer disease (AD) is a primary cause of cognitive dysfunction in the elderly population worldwide. Despite the allocation of enormous amounts of funding and resources to studying this brain disorder, there are no effective pharmacological treatments for reducing the severity of pathology and restoring cognitive function in affected people. Recent reports on the failure of multiple clinical trials for AD have highlighted the need to diversify further the search for new therapeutic strategies for cognitive dysfunction. Thus, studies detailing the neuroprotective effects of physical activity (PA) on the brain in AD were reviewed, and mechanisms by which PA might mitigate AD-related cognitive decline were explored. A MEDLINE database search was used to generate a list of studies conducted between January 2007 and September 2014 (n=394). These studies, along with key references, were screened to identify those that assessed the effects of PA on AD-related biomarkers and cognitive function. The search was not limited on the basis of intensity, frequency, duration, or mode of activity. However, studies in which PA was combined with another intervention (eg, diet, pharmacotherapeutics, ovariectomy, cognitive training, behavioral therapy), and studies not written in English were excluded. Thirty-eight animal and human studies met entry criteria. Most of the studies suggested that PA attenuates neuropathology and positively affects cognitive function in AD. Although the literature lacked sufficient evidence to support precise PA guidelines, convergent evidence does suggest that the incorporation of regular PA into daily routines mitigates AD-related symptoms, especially when deployed earlier in the disease process. Here the protocols used to alter the progression of AD-related neuropathology and cognitive decline are highlighted, and the implications for physical therapist practice are discussed.

  6. Link between plasminogen activator inhibitor-1 and cardiovascular risk in chronic hepatitis C after viral clearance

    PubMed Central

    Chang, Ming-Ling; Lin, Yu-sheng; Pao, Li-Heng; Huang, Hsin-Chih; Chiu, Cheng-Tang

    2017-01-01

    The pathophysiological implications of plasminogen activator inhibitor-1 (PAI-1) in HCV infection remain obscure. This prospective study evaluated 669 HCV patients, of whom 536 had completed a course of anti-HCV therapy and had pre-, peri- and post-therapy measurements of various profiles, including PAI-1 levels. Multivariate analysis demonstrated, before anti-HCV-therapy, platelet count and PAI-1-rs1799889 genotype were associated with PAI-1 levels. Among patients with a sustained virological response (SVR, n = 445), platelet count was associated with PAI-1 level at 24 weeks post-therapy. GEE analysis showed that PAI-1-rs-1799889 and interferon-λ3-rs12979860 genotypes affected PAI-1 levels early and late in therapy, respectively. At 24 weeks post-therapy, higher lipid, brain natriuretic peptide, homocysteine and PAI-1 levels and PAI-1 activity were noted only in SVR patients compared with pre-therapy levels. Within 24 weeks post-therapy, 2.2% of the SVR (mean age: 57.8 yr; 8 smoking males; the 2 females had pre-therapy hypercholesteremia or cardiovascular family history of disease) and 0% of the non-SVR patients experienced a new cardiovascular event. Platelet counts consistently correlated with PAI-1 levels regardless of HCV infection. PAI-1-rs-1799889 and interferon-λ3-rs12979860 genotypes mainly affected PAI-1 levels longitudinally. Within 24 weeks post-anti-HCV therapy, the SVR patients showed increasing PAI-1 levels with accelerating cardiovascular risk, especially the vulnerable cases. PMID:28211910

  7. What Are the Links of Prostate Cancer with Physical Activity and Nutrition? : A Systematic Review Article

    PubMed Central

    KRUK, Joanna; ABOUL-ENEIN, Hassan

    2016-01-01

    Background: Prostate cancer (PCa) is the second most common malignancy in men worldwide. The purpose of this study was to provide a brief synthesis the current knowledge for the effects of physical activity (PA) and nutrition on PCa risk. Methods: A systematic review of English languages reviews, meta-analysis, and original articles published from 2009 to 2015 extracted from the following websites: MEDLINE, Web of Science, Health Source, Science Direct, and their references. Results: The review of the literature led to the selection of 12 review or meta-analysis studies and 15 lately published observational studies. Most of studies reported relationship of recreational and occupational PA and vegetables, fruits, vitamins, red/processed meats, and fats consumption with risk of PCa. Decreased risk for PCa associated with exercise was reported in seven of the ten articles on this topic. The inverse association of vegetables and/or fruit intake with PCa risk was reported in eight of 13 papers. The effect of meat/fat intake on PCa was estimated in four articles finding increased risk. There was heterogeneity between studies, and findings are inconsistent. Conclusion: Physical activity does not significantly reduce the risk of PCa; however, vigorous exercise may reduce the risk of aggressive tumor. Besides, there is a lack of definitive evidence supporting the preventive role of diet against PCa. Due to many other benefits of regular moderate-vigorous PA and a diet high in vegetables and fruits and low in red/processed meats and fats, these lifestyle patterns may be recommended. PMID:28053921

  8. Chronic NF-κB activation links COPD and lung cancer through generation of an immunosuppressive microenvironment in the lungs

    PubMed Central

    Zaynagetdinov, Rinat; Sherrill, Taylor P.; Gleaves, Linda A.; Hunt, Pierre; Han, Wei; McLoed, Allyson G.; Saxon, Jamie A.; Tanjore, Harikrishna; Gulleman, Peter M.; Young, Lisa R.; Blackwell, Timothy S.

    2016-01-01

    Nuclear Factor (NF)-κB is positioned to provide the interface between COPD and carcinogenesis through regulation of chronic inflammation in the lungs. Using a tetracycline-inducible transgenic mouse model that conditionally expresses activated IκB kinase β (IKKβ) in airway epithelium (IKTA), we found that sustained NF-κB signaling results in chronic inflammation and emphysema by 4 months. By 11 months of transgene activation, IKTA mice develop lung adenomas. Investigation of lung inflammation in IKTA mice revealed a substantial increase in M2-polarized macrophages and CD4+/CD25+/FoxP3+ regulatory T lymphocytes (Tregs). Depletion of alveolar macrophages in IKTA mice reduced Tregs, increased lung CD8+ lymphocytes, and reduced tumor numbers following treatment with the carcinogen urethane. Alveolar macrophages from IKTA mice supported increased generation of inducible Foxp3+ Tregs ex vivo through expression of TGFβ and IL-10. Targeting of TGFβ and IL-10 reduced the ability of alveolar macrophages from IKTA mice to induce Foxp3 expression on T cells. These studies indicate that sustained activation of NF-κB pathway links COPD and lung cancer through generation and maintenance of a pro-tumorigenic inflammatory environment consisting of alternatively activated macrophages and regulatory T cells. PMID:26756215

  9. Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes.

    PubMed

    Platani, Melpomeni; Trinkle-Mulcahy, Laura; Porter, Michael; Jeyaprakash, A Arockia; Earnshaw, William C

    2015-07-06

    Coordination of cell growth and proliferation in response to nutrient supply is mediated by mammalian target of rapamycin (mTOR) signaling. In this study, we report that Mio, a highly conserved member of the SEACAT/GATOR2 complex necessary for the activation of mTORC1 kinase, plays a critical role in mitotic spindle formation and subsequent chromosome segregation by regulating the proper concentration of active key mitotic kinases Plk1 and Aurora A at centrosomes and spindle poles. Mio-depleted cells showed reduced activation of Plk1 and Aurora A kinase at spindle poles and an impaired localization of MCAK and HURP, two key regulators of mitotic spindle formation and known substrates of Aurora A kinase, resulting in spindle assembly and cytokinesis defects. Our results indicate that a major function of Mio in mitosis is to regulate the activation/deactivation of Plk1 and Aurora A, possibly by linking them to mTOR signaling in a pathway to promote faithful mitotic progression.

  10. Ferredoxin-thioredoxin reductase: a catalytically active dithiol group links photoreduced ferredoxin to thioredoxin functional in photosynthetic enzyme regulation

    SciTech Connect

    Droux, M.; Miginiac-Maslow, M.; Jacquot, J.P.; Gadal, P.; Crawford, N.A.; Kosower, N.S.; Buchanan, B.B.

    1987-07-01

    The mechanism by which the ferredoxin-thioredoxin system activates the target enzyme, NADP-malate dehydrogenase, was investigated by analyzing the sulfhydryl status of individual protein components with (/sup 14/C)iodoacetate and monobromobimane. The data indicate that ferredoxin-thioredoxin reductase (FTR)--an iron-sulfur enzyme present in oxygenic photosynthetic organisms--is the first member of a thiol chain that links light to enzyme regulation. FTR possesses a catalytically active dithiol group localized on the 13 kDa (similar) subunit, that occurs in all species investigated and accepts reducing equivalents from photoreduced ferredoxin and transfers them stoichiometrically to the disulfide form of thioredoxin m. The reduced thioredoxin m, in turn, reduces NADP-malate dehydrogenase, thereby converting it from an inactive (S-S) to an active (SH) form. The means by which FTR is able to combine electrons (from photoreduced ferredoxin) with protons (from the medium) to reduce its active disulfide group remains to be determined.

  11. Novel DLK-independent neuronal regeneration in Caenorhabditis elegans shares links with activity-dependent ectopic outgrowth

    PubMed Central

    Awal, Mehraj R.; Shay, James; McLoed, Melissa M.; Mazur, Eric; Gabel, Christopher V.

    2016-01-01

    During development, a neuron transitions from a state of rapid growth to a stable morphology, and neurons within the adult mammalian CNS lose their ability to effectively regenerate in response to injury. Here, we identify a novel form of neuronal regeneration, which is remarkably independent of DLK-1/DLK, KGB-1/JNK, and other MAPK signaling factors known to mediate regeneration in Caenorhabditis elegans, Drosophila, and mammals. This DLK-independent regeneration in C. elegans has direct genetic and molecular links to a well-studied form of endogenous activity-dependent ectopic axon outgrowth in the same neuron type. Both neuron outgrowth types are triggered by physical lesion of the sensory dendrite or mutations disrupting sensory activity, calcium signaling, or genes that restrict outgrowth during neuronal maturation, such as SAX-1/NDR kinase or UNC-43/CaMKII. These connections suggest that ectopic outgrowth represents a powerful platform for gene discovery in neuronal regeneration. Moreover, we note numerous similarities between C. elegans DLK-independent regeneration and lesion conditioning, a phenomenon producing robust regeneration in the mammalian CNS. Both regeneration types are triggered by lesion of a sensory neurite via reduction of neuronal activity and enhanced by disrupting L-type calcium channels or elevating cAMP. Taken as a whole, our study unites disparate forms of neuronal outgrowth to uncover fresh molecular insights into activity-dependent control of the adult nervous system’s intrinsic regenerative capacity. PMID:27078101

  12. Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes

    PubMed Central

    Trinkle-Mulcahy, Laura; Porter, Michael; Jeyaprakash, A. Arockia

    2015-01-01

    Coordination of cell growth and proliferation in response to nutrient supply is mediated by mammalian target of rapamycin (mTOR) signaling. In this study, we report that Mio, a highly conserved member of the SEACAT/GATOR2 complex necessary for the activation of mTORC1 kinase, plays a critical role in mitotic spindle formation and subsequent chromosome segregation by regulating the proper concentration of active key mitotic kinases Plk1 and Aurora A at centrosomes and spindle poles. Mio-depleted cells showed reduced activation of Plk1 and Aurora A kinase at spindle poles and an impaired localization of MCAK and HURP, two key regulators of mitotic spindle formation and known substrates of Aurora A kinase, resulting in spindle assembly and cytokinesis defects. Our results indicate that a major function of Mio in mitosis is to regulate the activation/deactivation of Plk1 and Aurora A, possibly by linking them to mTOR signaling in a pathway to promote faithful mitotic progression. PMID:26124292

  13. Chronic NF-κB activation links COPD and lung cancer through generation of an immunosuppressive microenvironment in the lungs.

    PubMed

    Zaynagetdinov, Rinat; Sherrill, Taylor P; Gleaves, Linda A; Hunt, Pierre; Han, Wei; McLoed, Allyson G; Saxon, Jamie A; Tanjore, Harikrishna; Gulleman, Peter M; Young, Lisa R; Blackwell, Timothy S

    2016-02-02

    Nuclear Factor (NF)-κB is positioned to provide the interface between COPD and carcinogenesis through regulation of chronic inflammation in the lungs. Using a tetracycline-inducible transgenic mouse model that conditionally expresses activated IκB kinase β (IKKβ) in airway epithelium (IKTA), we found that sustained NF-κB signaling results in chronic inflammation and emphysema by 4 months. By 11 months of transgene activation, IKTA mice develop lung adenomas. Investigation of lung inflammation in IKTA mice revealed a substantial increase in M2-polarized macrophages and CD4+/CD25+/FoxP3+ regulatory T lymphocytes (Tregs). Depletion of alveolar macrophages in IKTA mice reduced Tregs, increased lung CD8+ lymphocytes, and reduced tumor numbers following treatment with the carcinogen urethane. Alveolar macrophages from IKTA mice supported increased generation of inducible Foxp3+ Tregs ex vivo through expression of TGFβ and IL-10. Targeting of TGFβ and IL-10 reduced the ability of alveolar macrophages from IKTA mice to induce Foxp3 expression on T cells. These studies indicate that sustained activation of NF-κB pathway links COPD and lung cancer through generation and maintenance of a pro-tumorigenic inflammatory environment consisting of alternatively activated macrophages and regulatory T cells.

  14. HTLV-1 Tax Induces Formation of the Active Macromolecular IKK Complex by Generating Lys63- and Met1-Linked Hybrid Polyubiquitin Chains.

    PubMed

    Shibata, Yuri; Tokunaga, Fuminori; Goto, Eiji; Komatsu, Ginga; Gohda, Jin; Saeki, Yasushi; Tanaka, Keiji; Takahashi, Hirotaka; Sawasaki, Tatsuya; Inoue, Satoshi; Oshiumi, Hiroyuki; Seya, Tsukasa; Nakano, Hiroyasu; Tanaka, Yuetsu; Iwai, Kazuhiro; Inoue, Jun-Ichiro

    2017-01-01

    The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is crucial for the development of adult T-cell leukemia (ATL), a highly malignant CD4+ T cell neoplasm. Among the multiple aberrant Tax-induced effects on cellular processes, persistent activation of transcription factor NF-κB, which is activated only transiently upon physiological stimulation, is essential for leukemogenesis. We and others have shown that Tax induces activation of the IκB kinase (IKK) complex, which is a critical step in NF-κB activation, by generating Lys63-linked polyubiquitin chains. However, the molecular mechanism underlying Tax-induced IKK activation is controversial and not fully understood. Here, we demonstrate that Tax recruits linear (Met1-linked) ubiquitin chain assembly complex (LUBAC) to the IKK complex and that Tax fails to induce IKK activation in cells that lack LUBAC activity. Mass spectrometric analyses revealed that both Lys63-linked and Met1-linked polyubiquitin chains are associated with the IKK complex. Furthermore, treatment of the IKK-associated polyubiquitin chains with Met1-linked-chain-specific deubiquitinase (OTULIN) resulted in the reduction of high molecular weight polyubiquitin chains and the generation of short Lys63-linked ubiquitin chains, indicating that Tax can induce the generation of Lys63- and Met1-linked hybrid polyubiquitin chains. We also demonstrate that Tax induces formation of the active macromolecular IKK complex and that the blocking of Tax-induced polyubiquitin chain synthesis inhibited formation of the macromolecular complex. Taken together, these results lead us to propose a novel model in which the hybrid-chain-dependent oligomerization of the IKK complex triggered by Tax leads to trans-autophosphorylation-mediated IKK activation.

  15. HTLV-1 Tax Induces Formation of the Active Macromolecular IKK Complex by Generating Lys63- and Met1-Linked Hybrid Polyubiquitin Chains

    PubMed Central

    Tokunaga, Fuminori; Goto, Eiji; Komatsu, Ginga; Saeki, Yasushi; Tanaka, Keiji; Takahashi, Hirotaka; Sawasaki, Tatsuya; Inoue, Satoshi; Oshiumi, Hiroyuki; Seya, Tsukasa; Nakano, Hiroyasu; Tanaka, Yuetsu; Iwai, Kazuhiro

    2017-01-01

    The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is crucial for the development of adult T-cell leukemia (ATL), a highly malignant CD4+ T cell neoplasm. Among the multiple aberrant Tax-induced effects on cellular processes, persistent activation of transcription factor NF-κB, which is activated only transiently upon physiological stimulation, is essential for leukemogenesis. We and others have shown that Tax induces activation of the IκB kinase (IKK) complex, which is a critical step in NF-κB activation, by generating Lys63-linked polyubiquitin chains. However, the molecular mechanism underlying Tax-induced IKK activation is controversial and not fully understood. Here, we demonstrate that Tax recruits linear (Met1-linked) ubiquitin chain assembly complex (LUBAC) to the IKK complex and that Tax fails to induce IKK activation in cells that lack LUBAC activity. Mass spectrometric analyses revealed that both Lys63-linked and Met1-linked polyubiquitin chains are associated with the IKK complex. Furthermore, treatment of the IKK-associated polyubiquitin chains with Met1-linked-chain-specific deubiquitinase (OTULIN) resulted in the reduction of high molecular weight polyubiquitin chains and the generation of short Lys63-linked ubiquitin chains, indicating that Tax can induce the generation of Lys63- and Met1-linked hybrid polyubiquitin chains. We also demonstrate that Tax induces formation of the active macromolecular IKK complex and that the blocking of Tax-induced polyubiquitin chain synthesis inhibited formation of the macromolecular complex. Taken together, these results lead us to propose a novel model in which the hybrid-chain-dependent oligomerization of the IKK complex triggered by Tax leads to trans-autophosphorylation-mediated IKK activation. PMID:28103322

  16. Brain Activity and Network Interactions Linked to Valence-Related Differences in the Impact of Emotional Distraction.

    PubMed

    Iordan, A D; Dolcos, F

    2015-11-04

    Previous investigations showed that the impact of negative distraction on cognitive processing is linked to increased activation in a ventral affective system (VAS) and simultaneous deactivation in a dorsal executive system (DES). However, less is known about the influences of positive valence and different arousal levels on these effects. FMRI data were recorded while participants performed a working memory (WM) task, with positive and negative pictures presented as distracters during the delay between the memoranda and probes. First, positive distraction had reduced impact on WM performance, compared with negative distraction. Second, fMRI results identified valence-specific effects in DES regions and overlapping arousal and valence effects in VAS regions, suggesting increased impact of negative distraction and enhanced engagement of coping mechanisms for positive distraction. Third, a valence-related rostro-caudal dissociation was identified in medial frontal regions associated with the default-mode network (DMN). Finally, these DMN regions showed increased functional connectivity with DES regions for negative compared with positive distraction. Overall, these findings suggest that, while both positive and negative distraction engage partly similar arousal-dependent mechanisms, their differential impact on WM performance is linked to dissociations in the engagement of, and coupling between, regions associated with emotion processing and higher lever cognitive control.

  17. Using structural equation modeling to link human activities to wetland ecological integrity

    USGS Publications Warehouse

    Schweiger, E. William; Grace, James B.; Cooper, David; Bobowski, Ben; Britten, Mike

    2016-01-01

    The integrity of wetlands is of global concern. A common approach to evaluating ecological integrity involves bioassessment procedures that quantify the degree to which communities deviate from historical norms. While helpful, bioassessment provides little information about how altered conditions connect to community response. More detailed information is needed for conservation and restoration. We have illustrated an approach to addressing this challenge using structural equation modeling (SEM) and long-term monitoring data from Rocky Mountain National Park (RMNP). Wetlands in RMNP are threatened by a complex history of anthropogenic disturbance including direct alteration of hydrologic regimes; elimination of elk, wolves, and grizzly bears; reintroduction of elk (absent their primary predators); and the extirpation of beaver. More recently, nonnative moose were introduced to the region and have expanded into the park. Bioassessment suggests that up to half of the park's wetlands are not in reference condition. We developed and evaluated a general hypothesis about how human alterations influence wetland integrity and then develop a specific model using RMNP wetlands. Bioassessment revealed three bioindicators that appear to be highly sensitive to human disturbance (HD): (1) conservatism, (2) degree of invasion, and (3) cover of native forbs. SEM analyses suggest several ways human activities have impacted wetland integrity and the landscape of RMNP. First, degradation is highest where the combined effects of all types of direct HD have been the greatest (i.e., there is a general, overall effect). Second, specific HDs appear to create a “mixed-bag” of complex indirect effects, including reduced invasion and increased conservatism, but also reduced native forb cover. Some of these effects are associated with alterations to hydrologic regimes, while others are associated with altered shrub production. Third, landscape features created by historical beaver

  18. Dust Telescopes and Active Dust Collectors: Linking Dust to Their Sources

    NASA Astrophysics Data System (ADS)

    Drake, K. J.; Sternovsky, Z.; Gruen, E.; Srama, R.; Auer, S.; Horanyi, M.; Kempf, S.; Krueger, H.; Postberg, F.

    2010-12-01

    Cosmic dust particles from remote sites and times are treasures of information. By determining the dust particles' source and their elemental properties, we can learn about the environments, where they were formed and processed. Born as stardust in the cool atmospheres of giant stars or in novae and supernovae explosions, the particles are subsequently modified in the interstellar medium. Interplanetary dust that originates from comets and asteroids represents even more processed material at different stages of Solar System evolution. Interstellar and interplanetary dust particles from various sources can be detected and analyzed in the near-Earth space environment. The newly developed instruments Dust Telescope and Active Dust Collector are able to determine the origin of dust particles and provide their elemental composition. A Dust Telescope is a combination of a Dust Trajectory Sensor (DTS) [1] together with an analyzer for the chemical composition of dust particles in space. Dust particles' trajectories are determined by the measurement of induced electric signals when a charged grain flies through a position sensitive electrode system. A modern DTS can measure dust particles as small as 0.2 µm in radius and dust speeds up to 100 km/s. Large area chemical analyzers of 0.1 m2 sensitive area have been tested at a dust accelerator and it was demonstrated that they have sufficient mass resolution to resolve ions with atomic mass number up to >100 [2]. The advanced Dust Telescope is capable of identifying interstellar and interplanetary grains, and measuring their mass, velocity vector, charge, elemental and isotopic compositions. An Active Dust Collector combines a DTS with an aerogel or other dust collector materials, e.g. like the ones used on the Stardust mission. The combination of a DTS with a dust collector provides not only individual trajectories of the collected particles but also their impact time and position on the collector which proves essential to

  19. Development of a model for activated sludge aeration systems: linking air supply, distribution, and demand.

    PubMed

    Schraa, Oliver; Rieger, Leiv; Alex, Jens

    2017-02-01

    During the design of a water resource recovery facility, it is becoming industry practice to use simulation software to assist with process design. Aeration is one of the key components of the activated sludge process, and is one of the most important aspects of modelling wastewater treatment systems. However, aeration systems are typically not modelled in detail in most wastewater treatment process modelling studies. A comprehensive dynamic aeration system model has been developed that captures both air supply and demand. The model includes sub-models for blowers, pipes, fittings, and valves. An extended diffuser model predicts both oxygen transfer efficiency within an aeration basin and pressure drop across the diffusers. The aeration system model allows engineers to analyse aeration systems as a whole to determine biological air requirements, blower performance, air distribution, control valve impacts, controller design and tuning, and energy costs. This enables engineers to trouble-shoot the entire aeration system including process, equipment and controls. It also allows much more realistic design of these highly complex systems.

  20. Linking Existing Instruments to Develop an Activity of Daily Living Item Bank.

    PubMed

    Li, Chih-Ying; Romero, Sergio; Bonilha, Heather S; Simpson, Kit N; Simpson, Annie N; Hong, Ickpyo; Velozo, Craig A

    2016-11-16

    This study examined dimensionality and item-level psychometric properties of an item bank measuring activities of daily living (ADL) across inpatient rehabilitation facilities and community living centers. Common person equating method was used in the retrospective veterans data set. This study examined dimensionality, model fit, local independence, and monotonicity using factor analyses and fit statistics, principal component analysis (PCA), and differential item functioning (DIF) using Rasch analysis. Following the elimination of invalid data, 371 veterans who completed both the Functional Independence Measure (FIM) and minimum data set (MDS) within 6 days were retained. The FIM-MDS item bank demonstrated good internal consistency (Cronbach's α = .98) and met three rating scale diagnostic criteria and three of the four model fit statistics (comparative fit index/Tucker-Lewis index = 0.98, root mean square error of approximation = 0.14, and standardized root mean residual = 0.07). PCA of Rasch residuals showed the item bank explained 94.2% variance. The item bank covered the range of θ from -1.50 to 1.26 (item), -3.57 to 4.21 (person) with person strata of 6.3. The findings indicated the ADL physical function item bank constructed from FIM and MDS measured a single latent trait with overall acceptable item-level psychometric properties, suggesting that it is an appropriate source for developing efficient test forms such as short forms and computerized adaptive tests.

  1. Solar irradiance observed at Summit, Greenland: Possible links to magnetic activity on short timescales

    NASA Astrophysics Data System (ADS)

    Frederick, John E.

    2016-09-01

    Measurements of ground-level visible sunlight (400-600 nm) from Summit, Greenland over the period August 2004 through October 2014 define the attenuation provided by cloudiness, including its dependence on solar elevation and season. The long-term mean cloud-attenuation increases with increasing solar zenith angle, consistent with radiative transfer calculations which treat a cloud as a plane parallel layer with a strong bias toward forward scattering and an albedo for diffuse radiation near 0.1. The ratio of measured irradiance to clear-sky irradiance for solar zenith angles greater than 66° has a small, but statistically significant, positive correlation with the previous day's magnetic activity as measured by the daily Ap index, but no clear relationship exists between the irradiance ratio and daily changes in the ground-level neutron flux measured at Thule over the time frame considered. A high value of Ap on one day tends to be followed by a day whose ground-level solar irradiance is slightly greater than would occur otherwise. In an average sense, the visible irradiance following a day with Ap>16 exceeds that following a day with Ap≤16 by 1.2-1.3% with a 95% confidence range of approximately ±1.0%. The results are broadly compatible with small changes in atmospheric scattering following magnetic disturbances.

  2. Linking inter-individual differences in the perceptual load effect to spontaneous brain activity

    PubMed Central

    Liu, Lu; Tan, Jinfeng; Chen, Antao

    2015-01-01

    Previous researches have widely demonstrated that the interference from peripheral distractor will decrease when the task load is high. However, no study to date has paid attention to the individual differences in perceptual load effect (PLE) and little is known of spontaneous brain activity associated with PLE during resting state. To investigate this issue, we used resting-state functional Magnetic Resonance Imaging (fMRI) to examine the relationship between the amplitude of low-frequency fluctuations (ALFFs) and PLE. The results showed that there were large individual differences in PLE and we found PLE was significantly associated with ALFFs in left inferior temporal gyrus (ITG) and left precentral/postcentral gyrus. The present study suggested that the PLE was measurable, and there were individual differences in this effect. Moreover, these results implicated that: 1) mutual competition for limited capacity, which is involved in visual attention, and 2) response control that is included in behavior response both may contribute to the modulation induced by perceptual load. PMID:26257628

  3. Production of Extrachromosomal MicroDNAs Is Linked to Mismatch Repair Pathways and Transcriptional Activity.

    PubMed

    Dillon, Laura W; Kumar, Pankaj; Shibata, Yoshiyuki; Wang, Yuh-Hwa; Willcox, Smaranda; Griffith, Jack D; Pommier, Yves; Takeda, Shunichi; Dutta, Anindya

    2015-06-23

    MicroDNAs are <400-base extrachromosomal circles found in mammalian cells. Tens of thousands of microDNAs have been found in all tissue types, including sperm. MicroDNAs arise preferentially from areas with high gene density, GC content, and exon density from promoters with activating chromatin modifications and in sperm from the 5'-UTR of full-length LINE-1 elements, but are depleted from lamin-associated heterochromatin. Analysis of microDNAs from a set of human cancer cell lines revealed lineage-specific patterns of microDNA origins. A survey of microDNAs from chicken cells defective in various DNA repair proteins reveals that homologous recombination and non-homologous end joining repair pathways are not required for microDNA production. Deletion of the MSH3 DNA mismatch repair protein results in a significant decrease in microDNA abundance, specifically from non-CpG genomic regions. Thus, microDNAs arise as part of normal cellular physiology—either from DNA breaks associated with RNA metabolism or from replication slippage followed by mismatch repair.

  4. Opioids and efflux transporters. Part 3: P-glycoprotein substrate activity of 3-hydroxyl addition to meperidine analogs.

    PubMed

    Mercer, Susan L; Cunningham, Christopher W; Eddington, Natalie D; Coop, Andrew

    2008-06-15

    Numerous studies have shown that many clinically employed opioid analgesics are substrates for P-glycoprotein (P-gp), suggesting that up-regulation of P-gp may contribute to the development of central tolerance to opioids. The studies herein focus on the development of SAR for P-gp substrate activity in the meperidine series of opioids. Addition of a 3-OH to meperidine and the ketone analog of meperidine yielding bemidone and ketobemidone, respectively, significantly increased P-gp substrate affinity. The results of this study have implications in the development of novel analgesics to be utilized as tools to study the contribution of P-gp on the development of central tolerance to opioids.

  5. Addition of Al and Fe salts during treatment of paper mill effluents to improve activated sludge settlement characteristics.

    PubMed

    Agridiotis, V; Forster, C F; Carliell-Marquet, C

    2007-11-01

    Metal salts, ferrous sulphate and aluminium chloride, were added to laboratory-scale activated sludge plant treating paper mill effluents to investigate the effect on settlement characteristics. Before treatment the sludge was filamentous, had stirred sludge volume index (SSVI) values in excess of 300 and was moderately hydrophobic. The use of FeSO4.7H2O took three weeks to reduce the SSVI to 90. Microscopic examination showed that Fe had converted the filamentous flocs into a compact structure. When the iron dosing was stopped, the sludge returned to its bulking state within four weeks. In a subsequent trial, the addition of AlCl3 initially resulted in an improvement of the settlement index but then caused deterioration of the sludge properties. It is possible that aluminium was overdosed and caused charge reversal, increasing the SSVI.

  6. Mammary blood flow and metabolic activity are linked by a feedback mechanism involving nitric oxide synthesis.

    PubMed

    Cieslar, S R L; Madsen, T G; Purdie, N G; Trout, D R; Osborne, V R; Cant, J P

    2014-01-01

    To test which, if any, of the major milk precursors can elicit a rapid change in the rate of mammary blood flow (MBF) and to define the time course and magnitude of such changes, 4 lactating cows were infused with glucose, amino acids, or triacylglycerol into the external iliac artery feeding one udder half while iliac plasma flow (IPF) was monitored continuously by dye dilution. Adenosine and saline were infused as positive and negative controls, respectively, and insulin was infused to characterize the response to a centrally produced anabolic hormone. To test the roles of cyclooxygenase, NO synthase and ATP-sensitive K (KATP) channels in nutrient-mediated changes in blood flow, their respective inhibitors-indomethacin, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), and glibenclamide-were infused simultaneously with glucose. Each day, 1 infusate was given twice to each cow, over a 20-min period each time, separated by a 20-min washout period. In addition, each treatment protocol was administered on 2 separate days. A 73% increase in IPF during adenosine infusion showed that the mammary vasodilatory response was quadratic in time, with most changes occurring in the first 5min. Glucose infusion decreased IPF by 9% in a quadratic manner, most rapidly in the first 5min, indicating that a feedback mechanism of local blood flow control, likely through adenosine release, was operative in the mammary vasculature. Amino acid infusion increased IPF 9% in a linear manner, suggesting that mammary ATP utilization was stimulated more than ATP production. This could reflect a stimulation of protein synthesis. Triacylglycerol only tended to decrease IPF and insulin did not affect IPF. A lack of IPF response to glibenclamide indicates that KATP channels are not involved in MBF regulation. Indomethacin and L-NAME both depressed IPF. In the presence of indomethacin, glucose infusion caused a quadratic 9% increase in IPF. Indomethacin is an inhibitor of mitochondrial

  7. Activation of Phosphatidylinositol-Linked Dopamine Receptors Induces a Facilitation of Glutamate-Mediated Synaptic Transmission in the Lateral Entorhinal Cortex

    PubMed Central

    Glovaci, Iulia; Chapman, C. Andrew

    2015-01-01

    The lateral entorhinal cortex receives strong inputs from midbrain dopamine neurons that can modulate its sensory and mnemonic function. We have previously demonstrated that 1 µM dopamine facilitates synaptic transmission in layer II entorhinal cortex cells via activation of D1-like receptors, increased cAMP-PKA activity, and a resulting enhancement of AMPA-receptor mediated currents. The present study assessed the contribution of phosphatidylinositol (PI)-linked D1 receptors to the dopaminergic facilitation of transmission in layer II of the rat entorhinal cortex, and the involvement of phospholipase C activity and release of calcium from internal stores. Whole-cell patch-clamp recordings of glutamate-mediated evoked excitatory postsynaptic currents were obtained from pyramidal and fan cells. Activation of D1-like receptors using SKF38393, SKF83959, or 1 µM dopamine induced a reversible facilitation of EPSCs which was abolished by loading cells with either the phospholipase C inhibitor U-73122 or the Ca2+ chelator BAPTA. Neither the L-type voltage-gated Ca2+ channel blocker nifedipine, nor the L/N-type channel blocker cilnidipine, blocked the facilitation of synaptic currents. However, the facilitation was blocked by blocking Ca2+ release from internal stores via inositol 1,4,5-trisphosphate (InsP3) receptors or ryanodine receptors. Follow-up studies demonstrated that inhibiting CaMKII activity with KN-93 failed to block the facilitation, but that application of the protein kinase C inhibitor PKC(19-36) completely blocked the dopamine-induced facilitation. Overall, in addition to our previous report indicating a role for the cAMP-PKA pathway in dopamine-induced facilitation of synaptic transmission, we demonstrate here that the dopaminergic facilitation of synaptic responses in layer II entorhinal neurons also relies on a signaling cascade dependent on PI-linked D1 receptors, PLC, release of Ca2+ from internal stores, and PKC activation which is likely dependent

  8. The use of nanometer tetrabasic lead sulfate as positive active material additive for valve regulated lead-acid battery

    NASA Astrophysics Data System (ADS)

    Lang, Xiaoshi; Wang, Dianlong; Hu, Chiyu; Tang, Shenzhi; Zhu, Junsheng; Guo, Chenfeng

    2014-12-01

    Conventional tetrabasic lead sulfate used as positive active material additive shows the results of the low effective lead dioxide conversion rate due to the large grain size and crossed the crystal structure. In this paper, we study on a type of nanometer tetrabasic lead sulfate. Through the XRD and SEM test and Material Studio software calculation, the purity of tetrabasic lead sulfate is very high, the grain size of the nanometer 4BS is almost unanimous, and can be controlled below 200 nm. When charged and discharged in 1.75 V-2.42 V with the current density of 40 mA g-1, 80 mA g-1 and 160 mA g-1, the effective lead dioxide conversion rate of nanometer 4BS after formation can achieve to 83.48%, 71.42%, and 66.96%. Subsequently, the nanometer 4BS as additive is added to positive paste of lead-acid battery. When the batteries are tested galvanostatically between 1.75 V and 2.42 V at 0.25 C charge and 0.5 C discharge rates at room temperature. The ratio of adding nanometer 4BS is 0%, 1% and 4% and the initial discharge specific capacities are 60 mAh g-1, 65 mAh g-1 and 68 mAh g-1. After 80 cycles, the initial discharge capacity of positive active material with 1% nanometer 4BS decreased less than 10%, while adding 4% nanometer 4BS, the initial discharge capacity doesn't decrease obviously.

  9. Addition of Ascorbic Acid to the Extracellular Environment Activates Lipoplexes of a Ferrocenyl Lipid and Promotes Cell Transfection

    PubMed Central

    Aytar, Burcu S.; Muller, John P. E.; Golan, Sharon; Hata, Shinichi; Takahashi, Hiro; Kondo, Yukishige; Talmon, Yeshayahu; Abbott, Nicholas L.; Lynn, David M.

    2011-01-01

    The level of cell transfection mediated by lipoplexes formed using the ferrocenyl lipid bis(11-ferrocenylundecyl)dimethylammonium bromide (BFDMA) depends strongly on the oxidation state of the two ferrocenyl groups of the lipid (reduced BFDMA generally mediates high levels of transfection, but oxidized BFDMA mediates very low levels of transfection). Here, we report that it is possible to chemically transform inactive lipoplexes (formed using oxidized BFMDA) to “active” lipoplexes that mediate high levels of transfection by treatment with the small-molecule reducing agent ascorbic acid (vitamin C). Our results demonstrate that this transformation can be conducted in cell culture media and in the presence of cells by addition of ascorbic acid to lipoplex-containing media in which cells are growing. Treatment of lipoplexes of oxidized BFDMA with ascorbic acid resulted in lipoplexes composed of reduced BFDMA, as characterized by UV/vis spectrophotometry, and lead to activated lipoplexes that mediated high levels of transgene expression in the COS-7, HEK 293T/17, HeLa, and NIH 3T3 cell lines. Characterization of internalization of DNA by confocal microscopy and measurements of the zeta potentials of lipoplexes suggested that these large differences in cell transfection result from (i) differences in the extents to which these lipoplexes are internalized by cells and (ii) changes in the oxidation state of BFDMA that occur in the extracellular environment (i.e., prior to internalization of lipoplexes by cells). Characterization of lipoplexes by small-angle neutron scattering (SANS) and by cryogenic transmission electron microscopy (cryo-TEM) revealed changes in the nanostructures of lipoplexes upon the addition of ascorbic acid, from aggregates that were generally amorphous, to aggregates with a more extensive multilamellar nanostructure. The results of this study provide guidance for the design of redox-active lipids that could lead to methods that enable spatial

  10. Prediabetes linked to excess glucagon in transgenic mice with pancreatic active AKT1.

    PubMed

    Albury-Warren, Toya M; Pandey, Veethika; Spinel, Lina P; Masternak, Michal M; Altomare, Deborah A

    2016-01-01

    Protein kinase B/AKT has three isoforms (AKT1-3) and is renowned for its central role in the regulation of cell growth and proliferation, due to its constitutive activation in various cancers. AKT2, which is highly expressed in insulin-responsive tissues, has been identified as a primary regulator of glucose metabolism as Akt2 knockout mice (Akt2(-/-)) are glucose-intolerant and insulin-resistant. However, the role of AKT1 in glucose metabolism is not as clearly defined. We previously showed that mice with myristoylated Akt1 (AKT1(Myr)) expressed through a bicistronic Pdx1-TetA and TetO-MyrAkt1 system were susceptible to islet cell carcinomas, and in this study we characterized an early onset, prediabetic phenotype. Beginning at weaning (3 weeks of age), the glucose-intolerant AKT1(Myr) mice exhibited non-fasted hyperglycemia, which progressed to fasted hyperglycemia by 5 months of age. The glucose intolerance was attributed to a fasted hyperglucagonemia, and hepatic insulin resistance detectable by reduced phosphorylation of the insulin receptor following insulin injection into the inferior vena cava. In contrast, treatment with doxycycline diet to turn off the transgene caused attenuation of the non-fasted and fasted hyperglycemia, thus affirming AKT1 hyperactivation as the trigger. Collectively, this model highlights a novel glucagon-mediated mechanism by which AKT1 hyperactivation affects glucose homeostasis and provides an avenue to better delineate the molecular mechanisms responsible for diabetes mellitus and the potential association with pancreatic cancer.

  11. Prematurity, Birth Weight, and Socioeconomic Status Are Linked to Atypical Diurnal Hypothalamic-Pituitary-Adrenal Axis Activity in Young Adults.

    PubMed

    Winchester, Suzy Barcelos; Sullivan, Mary C; Roberts, Mary B; Granger, Douglas A

    2016-02-01

    In a prospective, case-controlled longitudinal design, 180 preterm and fullterm infants who had been enrolled at birth participated in a comprehensive assessment battery at age 23. Of these, 149 young adults, 34 formerly full-term and 115 formerly preterm (22 healthy preterm, 48 with medical complications, 21 with neurological complications, and 24 small for gestational age) donated five saliva samples from a single day that were assayed for cortisol to assess diurnal variation of the hypothalamic-pituitary-adrenal (HPA) axis. Analyses were conducted to determine whether prematurity category, birth weight, and socioeconomic status were associated with differences in HPA axis function. Pre- and perinatal circumstances associated with prematurity influenced the activity of this environmentally sensitive physiological system. Results are consistent with the theory of Developmental Origins of Health and Disease and highlight a possible mechanism for the link between prematurity and health disparities later in life.

  12. Application of the Principle of Linked Functions to ATP-Driven Ion Pumps: Kinetics of Activation by ATP

    NASA Astrophysics Data System (ADS)

    Reynolds, Jacqueline A.; Johnson, Edward A.; Tanford, Charles

    1985-06-01

    If a ligand binds with unequal affinity to two distinct states of a protein, then the equilibrium between the two states becomes a function of the concentration of the ligand. A necessary consequence is that the ligand must also affect the forward and/or reverse rate constants for transition between the two states. For an enzyme or transport protein with such a transition as a slow step in the catalytic cycle, the overall rate also becomes a function of ligand concentration. These conclusions are independent of whether or not the ligand is a direct participant in the reaction. If it is a direct partitipant, then the kinetic effect arising from the principle of linked functions is distinct from the direct catalytic effect. These principles suffice to account for the biphasic response of the hydrolytic activity of ATP-driven ion pumps to the concentration of ATP, without the need to invoke more than one ATP binding site per catalytic center.

  13. Appropriate Fe (II) Addition Significantly Enhances Anaerobic Ammonium Oxidation (Anammox) Activity through Improving the Bacterial Growth Rate

    PubMed Central

    Liu, Yiwen; Ni, Bing-Jie

    2015-01-01

    The application of anaerobic ammonium oxidation (Anammox) process is often limited by the slow growth rate of Anammox bacteria. As the essential substrate element that required for culturing Anammox sludge, Fe (II) is expected to affect Anammox bacterial growth. This work systematically studied the effects of Fe (II) addition on Anammox activity based on the kinetic analysis of specific growth rate using data from batch tests with an enriched Anammox sludge at different dosing levels. Results clearly demonstrated that appropriate Fe (II) dosing (i.e., 0.09 mM) significantly enhanced the specific Anammox growth rate up to 0.172 d−1 compared to 0.118 d−1 at regular Fe (II) level (0.03 mM). The relationship between Fe (II) concentration and specific Anammox growth rate was found to be well described by typical substrate inhibition kinetics, which was integrated into currently well-established Anammox model to describe the enhanced Anammox growth with Fe (II) addition. The validity of the integrated Anammox model was verified using long-term experimental data from three independent Anammox reactors with different Fe (II) dosing levels. This Fe (II)-based approach could be potentially implemented to enhance the process rate for possible mainstream application of Anammox technology, in order for an energy autarchic wastewater treatment. PMID:25644239

  14. Bacterial biodegradation of melamine-contaminated aged soil: influence of different pre-culture media or addition of activation material.

    PubMed

    Hatakeyama, Takashi; Takagi, Kazuhiro

    2016-08-01

    This study aimed to investigate the biodegrading potential of Arthrobacter sp. MCO, Arthrobacter sp. CSP, and Nocardioides sp. ATD6 in melamine-contaminated upland soil (melamine: approx. 10.5 mg/kg dry weight) after 30 days of incubation. The soil sample used in this study had undergone annual treatment of lime nitrogen, which included melamine; it was aged for more than 10 years in field. When R2A broth was used as the pre-culture medium, Arthrobacter sp. MCO could degrade 55 % of melamine after 30 days of incubation, but the other strains could hardly degrade melamine (approximately 25 %). The addition of trimethylglycine (betaine) in soil as an activation material enhanced the degradation rate of melamine by each strain; more than 50 % of melamine was degraded by all strains after 30 days of incubation. In particular, strain MCO could degrade 72 % of melamine. When the strains were pre-cultured in R2A broth containing melamine, the degradation rate of melamine in soil increased remarkably. The highest (72 %) melamine degradation rate was noted when strain MCO was used with betaine addition.

  15. CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase

    PubMed Central

    He, Weiwei; Bai, Ge; Zhou, Huihao; Wei, Na; White, Nicholas M.; Lauer, Janelle; Liu, Huaqing; Shi, Yi; Dumitru, Calin Dan; Lettieri, Karen; Shubayev, Veronica; Jordanova, Albena; Guergueltcheva, Velina; Griffin, Patrick R.; Burgess, Robert W.; Pfaff, Samuel L.; Yang, Xiang-Lei

    2015-01-01

    Summary Selective neuronal loss is a hallmark of neurodegenerative diseases, which counter-intuitively are often caused by mutations in widely-expressed genes1. Charcot-Marie-Tooth (CMT) diseases are the most common hereditary peripheral neuropathies, for which there are no effective therapies2,3. A subtype of the diseases—CMT2D—is caused by dominant mutations in GARS, encoding the ubiquitously expressed enzyme glycyl-tRNA synthetase (GlyRS). Despite the broad requirement of GlyRS for protein biosynthesis in all cells, mutations in this gene cause a selective degeneration of peripheral axons leading to deficits in distal motor function4. How mutations in GlyRS (GlyRSCMT2D) are linked to motor neuron vulnerability has remained elusive. Here we report that GlyRSCMT2D acquires a neomorphic binding activity that directly antagonizes an essential signaling pathway for motor neuron survival. We find that CMT2D mutations alter the conformation of GlyRS, enabling GlyRSCMT2D to bind the Neuropilin 1 (Nrp1) receptor. This aberrant interaction competitively interferes with the binding of the cognate ligand vascular endothelial growth factor (VEGF) to Nrp1. Genetic reduction of Nrp1 in mice worsens CMT2D symptoms, whereas enhanced expression of VEGF improves motor function. These findings link the selective pathology of CMT2D to the neomorphic binding activity of GlyRSCMT2D that antagonizes the VEGF/Nrp1 interaction, and indicate the VEGF/Nrp1 signaling axis is an actionable target for treating CMT2D. PMID:26503042

  16. Fc gamma receptor cross-linking activates p42, p38, and JNK/SAPK mitogen-activated protein kinases in murine macrophages: role for p42MAPK in Fc gamma receptor-stimulated TNF-alpha synthesis.

    PubMed

    Rose, D M; Winston, B W; Chan, E D; Riches, D W; Gerwins, P; Johnson, G L; Henson, P M

    1997-04-01

    Fc gamma R cross-linking on murine macrophages resulted in the activation of mitogen-activated protein kinase (MAPK) family members p42MAPK, p38, and c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase (SAPK). The temporal pattern of activation was distinct for each kinase. p42MAPK activation peaked at 5 min after receptor cross-linking, while peak p38 activity occurred 5 to 10 min later. Maximal JNK/SAPK activation occurred 20 min after Fc gamma R cross-linking. The selective MAPK/extracellular signal-regulated kinase-1 (MEK-1) inhibitor PD 098059 inhibited activation of p42MAPK induced by Fc gamma R cross-linking, but not p38 or JNK/SAPK activation. PD 098059 also inhibited the synthesis of TNF-alpha induced by Fc gamma R cross-linking (IC50 approximately 0.1 microM). Together, these results suggest that 1) the activation of MAPKs may play a role in Fc gammaR signal transduction, and 2) the activation of p42MAPK is necessary for Fc gamma R cross-linking-induced TNF-alpha synthesis.

  17. AN OBSERVED LINK BETWEEN ACTIVE GALACTIC NUCLEI AND VIOLENT DISK INSTABILITIES IN HIGH-REDSHIFT GALAXIES

    SciTech Connect

    Bournaud, Frederic; Juneau, Stephanie; Le Floc'h, Emeric; Mullaney, James; Daddi, Emanuele; Duc, Pierre-Alain; Elbaz, David; Salmi, Fadia; Dekel, Avishai; Dickinson, Mark

    2012-09-20

    We provide evidence for a correlation between the presence of giant clumps and the occurrence of active galactic nuclei (AGNs) in disk galaxies. Giant clumps of 10{sup 8}-10{sup 9} M{sub Sun} arise from violent gravitational instability in gas-rich galaxies, and it has been proposed that this instability could feed supermassive black holes (BHs). We use emission line diagnostics to compare a sample of 14 clumpy (unstable) disks and a sample of 13 smoother (stable) disks at redshift z {approx} 0.7. The majority of clumpy disks in our sample have a high probability of containing AGNs. Their [O III] {lambda}5007 emission line is strongly excited, inconsistent with low-metallicity star formation (SF) alone. [Ne III] {lambda}3869 excitation is also higher. Stable disks rarely have such properties. Stacking ultra sensitive Chandra observations (4 Ms) reveals an X-ray excess in clumpy galaxies, which confirms the presence of AGNs. The clumpy galaxies in our intermediate-redshift sample have properties typical of gas-rich disk galaxies rather than mergers, being in particular on the main sequence of SF. This suggests that our findings apply to the physically similar and numerous gas-rich unstable disks at z > 1. Using the observed [O III] and X-ray luminosities, we conservatively estimate that AGNs hosted by clumpy disks have typical bolometric luminosities of the order of a few 10{sup 43} erg s{sup -1}, BH growth rates m-dot{sub BH}{approx}10{sup -2} M{sub Sun} yr{sup -1}, and that these AGNs are substantially obscured in X-rays. This moderate-luminosity mode could provide a large fraction of today's BH mass with a high duty cycle (>10%), accretion bursts with higher luminosities being possible over shorter phases. Violent instabilities at high redshift (giant clumps) are a much more efficient driver of BH growth than the weak instabilities in nearby spirals (bars), and the evolution of disk instabilities with mass and redshift could explain the simultaneous downsizing of

  18. Role of the flavonoid-rich fraction in the antioxidant and cytotoxic activities of Bauhinia forficata Link. (Fabaceae) leaves extract.

    PubMed

    Miceli, Natalizia; Buongiorno, Luigina Pasqualina; Celi, Maria Grazia; Cacciola, Francesco; Dugo, Paola; Donato, Paola; Mondello, Luigi; Bonaccorsi, Irene; Taviano, Maria Fernanda

    2016-06-01

    Bauhinia forficata Link. is utilised as an antidiabetic in Brazilian folk-medicine; furthermore, its antioxidant properties suggest a potential usefulness in the prevention of diabetes complications associated with oxidative stress. The contribution of a flavonoid-rich fraction (FRF), HPLC-PDA-ESI-MS characterised, to the antioxidant and cytotoxic properties of B. forficata hydro-alcoholic leaves extract was evaluated for the first time. Both extract and FRF showed radical-scavenging activity and reducing power with a strong relationship with the flavonoid content found; hence, flavonoids are mainly responsible for the primary antioxidant activity of B. forficata extract. The extract significantly decreased FO-1 cell viability at the higher concentrations. FRF did not exert any effect; thus, flavonoids do not appear to be responsible for the cytotoxicity of the extract. The extract resulted virtually non-toxic against both Artemia salina and normal human lymphocytes, demonstrating potential selectivity in inhibiting cancer cell growth. Finally, no antimicrobial activity was observed against the bacteria and yeasts tested.

  19. Modeling the Effect of External Carbon Source Addition under Different Electron Acceptor Conditions in Biological Nutrient Removal Activated Sludge Systems.

    PubMed

    Hu, Xiang; Wisniewski, Kamil; Czerwionka, Krzysztof; Zhou, Qi; Xie, Li; Makinia, Jacek

    2016-02-16

    The aim of this study was to expand the International Water Association Activated Sludge Model No. 2d (ASM2d) to predict the aerobic/anoxic behavior of polyphosphate accumulating organisms (PAOs) and "ordinary" heterotrophs in the presence of different external carbon sources and electron acceptors. The following new aspects were considered: (1) a new type of the readily biodegradable substrate, not available for the anaerobic activity of PAOs, (2) nitrite as an electron acceptor, and (3) acclimation of "ordinary" heterotrophs to the new external substrate via enzyme synthesis. The expanded model incorporated 30 new or modified process rate equations. The model was evaluated against data from several, especially designed laboratory experiments which focused on the combined effects of different types of external carbon sources (acetate, ethanol and fusel oil) and electron acceptors (dissolved oxygen, nitrate and nitrite) on the behavior of PAOs and "ordinary" heterotrophs. With the proposed expansions, it was possible to improve some deficiencies of the ASM2d in predicting the behavior of biological nutrient removal (BNR) systems with the addition of external carbon sources, including the effect of acclimation to the new carbon source.

  20. Cardiac glycoside activities link Na(+)/K(+) ATPase ion-transport to breast cancer cell migration via correlative SAR.

    PubMed

    Magpusao, Anniefer N; Omolloh, George; Johnson, Joshua; Gascón, José; Peczuh, Mark W; Fenteany, Gabriel

    2015-02-20