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  1. Eliminating antibody polyreactivity through addition of N-linked glycosylation.

    PubMed

    Chuang, Gwo-Yu; Zhang, Baoshan; McKee, Krisha; O'Dell, Sijy; Kwon, Young Do; Zhou, Tongqing; Blinn, Julie; Lloyd, Krissey; Parks, Robert; Von Holle, Tarra; Ko, Sung-Youl; Kong, Wing-Pui; Pegu, Amarendra; Wang, Keyun; Baruah, Kavitha; Crispin, Max; Mascola, John R; Moody, M Anthony; Haynes, Barton F; Georgiev, Ivelin S; Kwong, Peter D

    2015-06-01

    Antibody polyreactivity can be an obstacle to translating a candidate antibody into a clinical product. Standard tests such as antibody binding to cardiolipin, HEp-2 cells, or nuclear antigens provide measures of polyreactivity, but its causes and the means to resolve are often unclear. Here we present a method for eliminating antibody polyreactivity through the computational design and genetic addition of N-linked glycosylation near known sites of polyreactivity. We used the HIV-1-neutralizing antibody, VRC07, as a test case, since efforts to increase VRC07 potency at three spatially distinct sites resulted in enhanced polyreactivity. The addition of N-linked glycans proximal to the polyreactivity-enhancing mutations at each of the spatially distinct sites resulted in reduced antibody polyreactivity as measured by (i) anti-cardiolipin ELISA, (ii) Luminex AtheNA Multi-Lyte ANA binding, and (iii) HEp-2 cell staining. The reduced polyreactivity trended with increased antibody concentration over time in mice, but not with improved overall protein stability as measured by differential scanning calorimetry. Moreover, glycan proximity to the site of polyreactivity appeared to be a critical factor. The results provide evidence that antibody polyreactivity can result from local, rather than global, features of an antibody and that addition of N-linked glycosylation can be an effective approach to reducing antibody polyreactivity.

  2. 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.

  3. 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

  4. 39 CFR 447.42 - Additional prohibited political activities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 39 Postal Service 1 2014-07-01 2014-07-01 false Additional prohibited political activities. 447.42... Political Activities § 447.42 Additional prohibited political activities. (a) In addition to the restrictions on political activities mentioned in § 447.51, an employee may not: (1) Display a...

  5. 39 CFR 447.42 - Additional prohibited political activities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Additional prohibited political activities. 447.42... Political Activities § 447.42 Additional prohibited political activities. (a) In addition to the restrictions on political activities mentioned in § 447.51, an employee may not: (1) Display a...

  6. 39 CFR 447.42 - Additional prohibited political activities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Additional prohibited political activities. 447.42... Political Activities § 447.42 Additional prohibited political activities. (a) In addition to the restrictions on political activities mentioned in § 447.51, an employee may not: (1) Display a...

  7. 39 CFR 447.42 - Additional prohibited political activities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 39 Postal Service 1 2011-07-01 2011-07-01 false Additional prohibited political activities. 447.42... Political Activities § 447.42 Additional prohibited political activities. (a) In addition to the restrictions on political activities mentioned in § 447.51, an employee may not: (1) Display a...

  8. 39 CFR 447.42 - Additional prohibited political activities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 39 Postal Service 1 2012-07-01 2012-07-01 false Additional prohibited political activities. 447.42... Political Activities § 447.42 Additional prohibited political activities. (a) In addition to the restrictions on political activities mentioned in § 447.51, an employee may not: (1) Display a...

  9. Civic Engagement Assessment: Linking Activities to Attitudes

    ERIC Educational Resources Information Center

    Terkla, Dawn Geronimo; O'Leary, Lisa S.; Wilson, Nancy E.; Diaz, Ande

    2007-01-01

    Recently, higher education has witnessed a renewed commitment to the mission of preparing students for lives of active citizenship. Under the leadership of President Lawrence S. Bacow, Tufts University (Medford, Massachusetts) has articulated an institutional mission that embraces three areas of focus: active citizenship, internationalism, and…

  10. Polymer-additive extraction via pressurized fluids and organic solvents of variously cross-linked poly(methylmethacrylates).

    PubMed

    Nazem, N; Taylor, L T

    2002-04-01

    Variously cross-linked poly(methylmethacrylates) (PMMAs) are synthesized with three additives incorporated at theoretically 1000 microg of the additive per gram of prepared polymer. The additives are Irganox 1010, Irganox 1076, and Irgafos 168. The in-house" synthesized polyacrylates are then subjected to supercritical fluid extraction (SFE) to determine if additive recovery is a function of percent cross-linking. Although considerable work in this regard has been performed with non-cross-linked polyolefins, the literature is lacking regarding polyacrylates. Some additive degradation apparently occurs during the synthesis, as judged by the increased complexity of the extract high-performance liquid chromatographic trace and the low percent recoveries observed especially for the Irganoxes. For low polymer cross-linking (1%), it appears that both PMMA synthetic reproducibility and readily observed polymer swelling during SFE are serious issues that adversely affect additive percent recovery and precision of results. Higher percent cross-linking yields more consistent analytical data than low percent cross-linking, even though the amount of additive extracted in all PMMA samples (regardless of cross-linking percentage) is essentially the same whether the extraction is via SFE or liquid-solid extraction with methylene chloride. Results for comparably cross-linked poly(ethylmethacrylate) and poly(butylmethacrylate) are similar to PMMA.

  11. 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

  12. 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…

  13. Prefrontal Activity Links Nonoverlapping Events in Memory

    PubMed Central

    Miyawaki, Hiroyuki; Helmstetter, Fred J.; Diba, Kamran

    2013-01-01

    The medial prefrontal cortex (mPFC) plays an important role in memory. By maintaining a working memory buffer, neurons in prelimbic (PL) mPFC may selectively contribute to learning associations between stimuli that are separated in time, as in trace fear conditioning (TFC). Until now, evidence for this bridging role was largely descriptive. Here we used optogenetics to silence neurons in the PL mPFC of rats during learning in TFC. Memory formation was prevented when mPFC was silenced specifically during the interval separating the cue and shock. Our results provide support for a working memory function for these cells and indicate that associating two noncontiguous stimuli requires bridging activity in PL mPFC. PMID:23804110

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

    PubMed

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

    2015-03-01

    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. 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.

  16. 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,…

  17. Synthesis and biological activity of new arenediyne-linked isoxazolidines.

    PubMed

    Romeo, Roberto; Navarra, Michele; Giofrè, Salvatore V; Carnovale, Caterina; Cirmi, Santa; Lanza, Giuseppe; Chiacchio, Maria A

    2014-07-01

    Arenediyne-isoxazolidine conjugates have been synthesized as a new scaffold for the development of bioactive mimics. Some of the synthesized compounds are endowed with antiproliferative activity against three human cancer cell lines. Their thermal reactivity suggests that the biological activity probably could not be linked to the Bergman cyclization.

  18. 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.

  19. Repeated games and direct reciprocity under active linking.

    PubMed

    Pacheco, Jorge M; Traulsen, Arne; Ohtsuki, Hisashi; Nowak, Martin A

    2008-02-21

    Direct reciprocity relies on repeated encounters between the same two individuals. Here we examine the evolution of cooperation under direct reciprocity in dynamically structured populations. Individuals occupy the vertices of a graph, undergoing repeated interactions with their partners via the edges of the graph. Unlike the traditional approach to evolutionary game theory, where individuals meet at random and have no control over the frequency or duration of interactions, we consider a model in which individuals differ in the rate at which they seek new interactions. Moreover, once a link between two individuals has formed, the productivity of this link is evaluated. Links can be broken off at different rates. Whenever the active dynamics of links is sufficiently fast, population structure leads to a simple transformation of the payoff matrix, effectively changing the game under consideration, and hence paving the way for reciprocators to dominate defectors. We derive analytical conditions for evolutionary stability.

  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 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.

  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. Identification of additional MAP kinases activated upon PAMP treatment

    PubMed Central

    Nitta, Yukino; Ding, Pingtao; Zhang, Yuelin

    2014-01-01

    Mitogen-activated protein (MAP) kinase cascades play important roles in plant immunity. Upon pathogen associated molecular pattern (PAMP) treatment, MPK3, MPK6 and MPK4 are quickly activated by upstream MKKs through phosphorylation. Western blot analysis using α-phospho-p44/42-ERK antibody suggests that additional MPKs with similar size as MPK4 are also activated upon PAMP perception. To identify these MAP kinases, 7 candidate MPKs with similar sizes as MPK4 were selected for further analysis. Transgenic plants expressing these MPKs with a ZZ-3xFLAG double tag of 17 kD were generated and analyzed by western blot. MPK1, MPK11 and MPK13 were found to be phosphorylated upon treatment with flg22. Our study revealed additional MAPKs being activated during PAMP-triggered immunity. PMID:25482788

  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. 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.

  6. 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.

  7. 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.

  8. Basophil Activation Test with Food Additives in Chronic Urticaria Patients

    PubMed Central

    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

    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. PMID:24527415

  9. 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

    2013-12-01

    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. PMID:24309271

  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

    2013-12-01

    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. Antiandrogenic activity of phthalate mixtures: validity of concentration addition.

    PubMed

    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(10), EC(25) and EC(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(10) mixtures BBP+DBP, BBP+DEP and DBP+DEP, and the EC(25) mixture of DBP+BPA. A ternary mixture revealed synergism at the EC(50), and weak antagonistic activity at the EC(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.

  12. Active link selection for efficient semi-supervised community detection.

    PubMed

    Yang, Liang; Jin, Di; Wang, Xiao; Cao, Xiaochun

    2015-01-01

    Several semi-supervised community detection algorithms have been proposed recently to improve the performance of traditional topology-based methods. However, most of them focus on how to integrate supervised information with topology information; few of them pay attention to which information is critical for performance improvement. This leads to large amounts of demand for supervised information, which is expensive or difficult to obtain in most fields. For this problem we propose an active link selection framework, that is we actively select the most uncertain and informative links for human labeling for the efficient utilization of the supervised information. We also disconnect the most likely inter-community edges to further improve the efficiency. Our main idea is that, by connecting uncertain nodes to their community hubs and disconnecting the inter-community edges, one can sharpen the block structure of adjacency matrix more efficiently than randomly labeling links as the existing methods did. Experiments on both synthetic and real networks demonstrate that our new approach significantly outperforms the existing methods in terms of the efficiency of using supervised information. It needs ~13% of the supervised information to achieve a performance similar to that of the original semi-supervised approaches. PMID:25761385

  13. Structural analysis of the varicella-zoster virus gp98-gp62 complex: posttranslational addition of N-linked and O-linked oligosaccharide moieties.

    PubMed

    Montalvo, E A; Parmley, R T; Grose, C

    1985-03-01

    Varicella-zoster virus specifies the formation of several glycoproteins, including the preponderant gp98-gp62 glycoprotein complex in the outer membranes of virus-infected cells. These viral glycoproteins are recognized and precipitated by a previously described monoclonal antibody designated monoclone 3B3. When an immunoblot analysis was performed, only gp98 was reactive with monoclone 3B3 antibody; likewise, titration in the presence of increased concentrations of sodium dodecyl sulfate during antigen-antibody incubations caused selective precipitation of gp98 but not gp62. Further structural analyses of gp98 were performed by using the glycosidases endo-beta-N-acetylglucosaminidase H (endoglycosidase H) and neuraminidase and two inhibitors of glycosylation (tunicamycin and monensin). In addition to gp98, antibody 3B3 reacted with several intermediate products, including gp90, gp88, gp81, and a nonglycosylated polypeptide, p73. Since gp98 was completely resistant to digestion with endoglycosidase H, it contained only complex carbohydrate moieties; conversely, gp81 contained mainly high-mannose residues. Polypeptide p73 was immunodetected in the presence of tunicamycin and designated as a nascent recipient of N-linked sugars, whereas gp88 was considered to contain O-linked oligosaccharides because its synthesis was not affected by tunicamycin. The ionophore monensin inhibited production of mature gp98, but other intermediate forms, including gp90, were detected. Since the latter product was similar in molecular weight to the desialated form of gp98, one effect of monensin treatment of varicella-zoster virus-infected cells was to block the addition of N-acetylneuraminic acid. Monensin also blocked insertion of gp98 into the plasma membrane and, as determined by electron microscopy, inhibited envelopment of the nucleocapsid and its transport within the cytoplasm. On the basis of this study, we reached the following conclusions: the primary antibody 3B3-binding

  14. Inflammation, Cancer and Oxidative Lipoxygenase Activity are Intimately Linked

    PubMed Central

    Wisastra, Rosalina; Dekker, Frank J.

    2014-01-01

    Cancer and inflammation are intimately linked due to specific oxidative processes in the tumor microenvironment. Lipoxygenases are a versatile class of oxidative enzymes involved in arachidonic acid metabolism. An increasing number of arachidonic acid metabolites is being discovered and apart from their classically recognized pro-inflammatory effects, anti-inflammatory effects are also being described in recent years. Interestingly, these lipid mediators are involved in activation of pro-inflammatory signal transduction pathways such as the nuclear factor κB (NF-κB) pathway, which illustrates the intimate link between lipid signaling and transcription factor activation. The identification of the role of arachidonic acid metabolites in several inflammatory diseases led to a significant drug discovery effort around arachidonic acid metabolizing enzymes. However, to date success in this area has been limited. This might be attributed to the lack of selectivity of the developed inhibitors and to a lack of detailed understanding of the functional roles of arachidonic acid metabolites in inflammatory responses and cancer. This calls for a more detailed investigation of the activity of arachidonic acid metabolizing enzymes and development of more selective inhibitors. PMID:25037020

  15. 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

  16. Cross-linking and modification of cytochrome c with redox-active metal complexes

    SciTech Connect

    Lukes, A.

    1991-05-02

    This thesis consists of two parts. The first part shows that a redox-active trinuclear metal cluster may be used as a cross-linking reagent for proteins. Electron transfer is observed in the protein oligomers. The second part involves labelling the cysteine residue of baker's yeast cytochrome c with chloromercuriferrocene. Chloromercuriferrocene reacts with cytochrome c in two interesting ways. Symmetrization produces two products; two proteins cross-linked with mercury and diferrocenylmercury. Simple substitution of FeHgCl onto the protein followed by the addition of a proton by electrophilic substitution affords ferrocene and the mercuric chloride modified protein. 16 refs., 3 figs.

  17. Linking geomagnetic activity and polar surface air temperature variability

    NASA Astrophysics Data System (ADS)

    Seppala, Annika

    ERA-40 and ECMWF operational surface level air temperature (SAT) data sets from 1957 to 2006 were used to examine polar temperature variations during years with different levels of geomagnetic activity, as defined by the Ap index. Previous modelling work has suggested that NOx produced at high latitudes by energetic particle precipitation can eventually lead to detectable changes in polar SATs. We find that during winter months, ERA-40 and ECMWF polar SATs in years with high Ap index are different than in years with low Ap index; the differences are statistically significant at the 2-sigma level and range up to about ±4.5 K, de-pending on location. The temperature differences are larger when years with wintertime Sudden Stratospheric Warmings are excluded. Solar irradiance variations were taken into account in the analysis. Although using the re-analysis and operational data sets it was not possible to conclusively show that the polar SAT patterns are physically linked by geomagnetic activity, we conclude that geomagnetic activity likely plays a role in modulating polar wintertime surface air temperature patterns. The SAT results were tested against variation in the Quasi Biennial Oscillation (QBO), the El Niño Southern Oscillation (ENSO) and the Southern Annular Mode n (SAM). The results suggested that these were not driving the observed polar SAT variability. However, significant uncertainty is introduced by the Northern Annular Mode (NAM) and we could not robustly exclude a chance linkage between sea surface temperature (SST) variability and geomagnetic activity. Examining the physical link between geomagnetic activity and polar surface temperature variability patterns using atmospheric models is an ongoing task.

  18. Enhancing antioxidant activity of sesamol at frying temperature by addition of additives through reducing volatility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Additives were evaluated to investigate their effects on volatility of sesamol at frying temperature with the hypothesis that the interaction between an additive and sesamol would reduce sesamol volatility. Twenty-two additive:sesamol combinations were examined by thermogravimetric analysis (TGA) un...

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

    PubMed

    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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

    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 C3S and β-C2S.

  7. 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

  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, 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...

  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. 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...

  12. Activities of citrate synthase and NAD+-linked and NADP+-linked isocitrate dehydrogenase in muscle from vertebrates and invertebrates.

    PubMed Central

    Alp, P R; Newsholme, E A; Zammit, V A

    1976-01-01

    1. The activities of citrate synthase, NAD+-linked and NADP+-linked isocitrate dehydrogenase were measured in muscles from a large number of animals, in order to provide some indication of the importance of the citric acid cycle in these muscles. According to the differences in enzyme activities, the muscles can be divided into three classes. First, in a number of both vertebrate and invertebrate muscles, the activities of all three enzymes are very low. It is suggested that either the muscles use energy at a very low rate or they rely largely on anaerobic glycolysis for higher rates of energy formation. Second, most insect flight muscles contain high activities of citrate synthase and NAD+-linked isocitrate dehydrogenase, but the activities of the NADP+-linked enzyme are very low. The high activities indicate the dependence of insect flight on energy generated via the citric acid cycle. The flight muscles of the beetles investigated contain high activities of both isocitrate dehydrogenases. Third, other muscles of both vertebrates and invertebrates contain high activities of citrate synthase and NADP+-liniked isocitrate dehydrogenase. Many, if not all, of these muscles are capable of sustained periods of mechanical activity (e.g. heart muscle, pectoral muscles of some birds). Consequently, to support this activity fuel must be supplied continually to the muscle via the circulatory system which, in most animals, also transports oxygen so that energy can be generated by complete oxidation of the fuel. It is suggested that the low activities of NAD+-linked isocitrate dehydrogenase in these muscles may be involved in oxidation of isocitrate in the cycle when the muscles are at rest. 2. A comparison of the maximal activities of the enzymes with the maximal flux through the cycle suggests that, in insect flight muscle, NAD+-linked isocitrate dehydrogenase catalyses a non-equilibrium reaction and citrate synthease catalyses a near-equilibrium reaction. In other muscles

  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. PMID:26267368

  14. 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.

  15. 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

  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. Startle activation is additive with voluntary cortical activation irrespective of stimulus modality.

    PubMed

    Maslovat, Dana; Drummond, Neil M; Carter, Michael J; Carlsen, Anthony N

    2015-10-01

    When a startling acoustic stimulus (SAS) is presented during a simple reaction time (RT) task, it can trigger the prepared response through an involuntary initiation pathway. Previous research modelling the effects of presenting a SAS at various intervals following a non-startling auditory imperative signal (IS) suggested that involuntary initiation-related neural activation is additive with the voluntary initiation processes. The current study tested the predictions of this additive model when the SAS and IS are of different modalities by using a visual rather than auditory go-signal. Because voluntary RT latencies are delayed for visual stimuli compared to acoustic stimuli, it was hypothesised that the time course of additive activation would be similarly delayed. Participants performed 150 RT trials requiring a targeted 20° wrist extension task with a SAS presented 0-125 ms following a visual go-signal. Results were not different to those predicted by an additive model (p=0.979), yet were significantly different to those predicted by a horse-race model (p=0.037), indicating a joint contribution of voluntary and involuntary activation, even when the IS and SAS are of different modalities. Furthermore, the results indicated that voluntary RT differences due to stimulus modality are attributable to processes that occur prior to the increase in initiation-related activation.

  19. 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.

  20. 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. PMID:26950749

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

    PubMed

    Carvalho, Waldemir M; Souza, Flavio L

    2016-09-01

    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.

  2. 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.

  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. Linked Active Content: A Service for Digital Libraries for Education.

    ERIC Educational Resources Information Center

    Yaron, David; Milton, D. Jeff; Freeland, Rebecca

    A service is described to help enable digital libraries for education, such as the NSDL (National Science Mathematics Engineering and Technology Education Digital Library), to serve as collaboration spaces for the creation, modification and use of active learning experiences. The goal is to redefine the line between those activities that fall…

  5. 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…

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

    SciTech Connect

    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.

  7. 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.

  8. 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. PMID:24962361

  9. Michael addition of dehydroalanine-containing MAPK peptides to catalytic lysine inhibits the activity of phosphothreonine lyase.

    PubMed

    Zhang, Yuan; Yang, Ru; Huang, Juan; Liang, Qiujin; Guo, Yanmin; Bian, Weixiang; Luo, Lingfei; Li, Hongtao

    2015-11-30

    The phosphothreonine lyases OspF and SpvC irreversibly inactivate host dual-phosphorylated mitogen-activated protein kinases (MAPKs) [pThr-X-pTyr motif] through β-elimination. We found that dual-phosphorylated (pSer-X-pTyr) MAPK substrate peptides and their resulting catalytic products cross-link to OspF and SpvC. Mass spectrometry results revealed that these linkages form between lysine, which acts as a general base, and dehydroalanine (Dha) on catalytic products. The nucleophilic addition efficiency is dependent on the K136 residue being in a deprotonated state. Peptide cross-linking inhibits the activity of SpvC and blocks the inactivation of MAPK signaling by SpvC. Small compounds mimicking these sequences may act as phosphothreonine lyase inhibitors. PMID:26519561

  10. 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…

  11. Conformational Stability and Catalytic Activity of PTEN Variants Linked to Cancers and Autism Spectrum Disorders

    PubMed Central

    Johnston, Sean B.; Raines, Ronald T.

    2015-01-01

    Phosphoinositides are membrane components that play critical regulatory roles in mammalian cells. The enzyme PTEN, which catalyzes the dephosphorylation of the phosphoinositide PIP3, is damaged in most sporadic tumors. Mutations in the PTEN gene have also been linked to autism spectrum disorders and other forms of delayed development. Here, human PTEN is shown to be on the cusp of unfolding under physiological conditions. Variants of human PTEN linked to somatic cancers and disorders on the autism spectrum are shown to be impaired in their conformational stability, catalytic activity, or both. Those variants linked only to autism have higher activity than those linked to cancers. PTEN-L, which is a secreted trans-active isoform, has greater conformational stability than does the wild-type enzyme. These data indicate that PTEN is a fragile enzyme cast in a crucial role in cellular metabolism, and suggest that PTEN-L is a repository for a critical catalytic activity. PMID:25647146

  12. 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

    2016-09-01

    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

  13. 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

    2011-01-01

    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. PMID:21573113

  14. 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.

  15. 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. PMID:22628652

  16. Linking lake variability, climate, and human activity in Basotu, Tanzania.

    NASA Astrophysics Data System (ADS)

    Higgins, Lindsey; Westerberg, Lars-Ove; Risberg, Jan

    2016-04-01

    Lake Basotu (4.3697°S, 35.0728°E) is a crater lake in north-central Tanzania. This lake is an important source of freshwater for local people as no perennial rivers are present. Due to intensive agricultural methods and climatic factors, lake level has fluctuated greatly over time. A history of environmental variability of the past 1800 years was established using the diatom record, magnetic parameters, and carbon content from a three meter long sediment core. Fluctuations in modern lake extent (1973 - 2015) were calculated using archived Landsat images and compared to meteorological records and documents of activity around the lake to determine the greatest impacts and their consequences on this essential water resource. Variations in the paleo-record indicate that fluctuations in lake level are not abnormal, however human influence has likely increased the sensitivity of Lake Basotu to climatic fluctuations.

  17. 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.

  18. 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

  19. Developmental Benefits of Extracurricular Involvement: Do Peer Characteristics Mediate the Link between Activities and Youth Outcomes?

    ERIC Educational Resources Information Center

    Fredricks, Jennifer A.; Eccles, Jacquelynn S.

    2005-01-01

    In this article, we test: (a) the relation between school-based extracurricular participation and indicators of positive and negative development across a range of activity contexts, and (b) a mediation model linking activity participation, prosocial peers, and development. Extensive survey information was collected from a predominately White…

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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

    2015-01-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    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.

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

    PubMed Central

    Tada, Yuya; Grossart, Hans-Peter

    2014-01-01

    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. PMID:23985742

  11. Morphology and optical properties of aluminum oxide formed into oxalic electrolyte with addition surface active agents

    NASA Astrophysics Data System (ADS)

    Kazarkin, B.; Stsiapanau, A.; Zhilinski, V.; Chernik, A.; Bezborodov, V.; Kozak, G.; Danilovich, S.; Smirnov, A.

    2016-08-01

    The article discusses the results of investigations of porous films of alumina, formed into oxalic electrolyte with addition surface active agents, in particular, ordering structure, roughness of a surface, the optical transparency of the electrolyte concentration and surface active agents. Also discusses the features of the formation of porous films of temperature and IR radiation.

  12. 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

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

    PubMed

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

    2016-04-01

    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.

  14. 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…

  15. Linking Europa’s Plume Activity to Tides, Tectonics, and Liquid Water

    NASA Astrophysics Data System (ADS)

    Rhoden, Alyssa R.; Hurford, Terry; Roth, Lorenz; Retherford, Kurt

    2014-11-01

    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, evidence of ongoing tidally-driven processes has been lacking. However, a recent observation of water vapor near Europa’s south pole suggests that it may be geologically active. Non-detections in previous and follow-up observations indicate a temporal variation in plume visibility and suggests a relationship to Europa’s tidal cycle. Similarly, the Cassini spacecraft has observed plumes emanating from the south pole of Saturn’s moon, Enceladus, and variability in the intensity of eruptions has been linked to its tidal cycle. The inference that a similar mechanism controls plumes at both Europa and Enceladus motivates further analysis of Europa’s plume behavior and the relationship between plumes, tides, and liquid water on these two satellites.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. In contrast, 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 the model faults are robust across a broad range of precession rates and spin pole directions. Analysis of the stress variations across model faults suggests that the plumes would be best observed earlier in Europa’s orbit. Our results indicate that Europa’s plumes, if

  16. Accommodation of GDP-Linked Sugars in the Active Site of GDP-Perosamine Synthase

    SciTech Connect

    Cook, Paul D.; Carney, Amanda E.; Holden, Hazel M.

    2009-01-12

    Perosamine (4-amino-4,6-dideoxy-d-mannose), or its N-acetylated form, is one of several dideoxy sugars found in the O-antigens of such infamous Gram-negative bacteria as Vibrio cholerae O1 and Escherichia coli O157:H7. It is added to the bacterial O-antigen via a nucleotide-linked version, namely GDP-perosamine. Three enzymes are required for the biosynthesis of GDP-perosamine starting from mannose 1-phosphate. The focus of this investigation is GDP-perosamine synthase from Caulobacter crescentus, which catalyzes the final step in GDP-perosamine synthesis, the conversion of GDP-4-keto-6-deoxymannose to GDP-perosamine. The enzyme is PLP-dependent and belongs to the aspartate aminotransferase superfamily. It contains the typically conserved active site lysine residue, which forms a Schiff base with the PLP cofactor. Two crystal structures were determined for this investigation: a site-directed mutant protein (K186A) complexed with GDP-perosamine and the wild-type enzyme complexed with an unnatural ligand, GDP-3-deoxyperosamine. These structures, determined to 1.6 and 1.7 {angstrom} resolution, respectively, revealed the manner in which products, and presumably substrates, are accommodated within the active site pocket of GDP-perosamine synthase. Additional kinetic analyses using both the natural and unnatural substrates revealed that the K{sub m} for the unnatural substrate was unperturbed relative to that of the natural substrate, but the k{sub cat} was lowered by a factor of approximately 200. Taken together, these studies shed light on why GDP-perosamine synthase functions as an aminotransferase whereas another very similar PLP-dependent enzyme, GDP-4-keto-6-deoxy-d-mannose 3-dehydratase or ColD, catalyzes a dehydration reaction using the same substrate.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Mental addition in bilinguals: an FMRI study of task-related and performance-related activation.

    PubMed

    Lin, Jo-Fu Lotus; Imada, Toshiaki; Kuhl, Patricia K

    2012-08-01

    Behavioral studies show that bilinguals are slower and less accurate when performing mental calculation in their nondominant (second; L2) language than in their dominant (first; L1) language. However, little is known about the neural correlates associated with the performance differences observed between bilinguals' 2 languages during arithmetic processing. To address the cortical activation differences between languages, the current study examined task-related and performance-related brain activation during mental addition when problems were presented auditorily in participants' L1 and L2. Eleven Chinese-English bilinguals heard 2-digit addition problems that required exact or approximate calculations. Functional magnetic resonance imaging results showed that auditorily presented multidigit addition in bilinguals activates bilateral inferior parietal and inferior frontal regions in both L1 and L2. Language differences were observed in the form of greater activation for L2 exact addition in the left inferior frontal area. A negative correlation between brain activation and behavioral performance during mental addition in L2 was observed in the left inferior parietal area. Current results provide further evidence for the effects of language-specific experience on arithmetic processing in bilinguals at the cortical level.

  2. Intramembrane Proton Binding Site Linked to Activation of Bacterial Pentameric Ion Channel*

    PubMed Central

    Wang, Hai-Long; Cheng, Xiaolin; Sine, Steven M.

    2012-01-01

    Prokaryotic orthologs of eukaryotic Cys-loop receptor channels recently emerged as structural and mechanistic surrogates to investigate this superfamily of intercellular signaling proteins. Here, we examine proton activation of the prokaryotic ortholog GLIC using patch clamp electrophysiology, mutagenesis, and molecular dynamics (MD) simulations. Whole-cell current recordings from human embryonic kidney (HEK) 293 cells expressing GLIC show half-maximal activation at pH 6, close to the pKa of histidine, implicating the three native His residues in proton sensing linked to activation. The mutation H235F abolishes proton activation, H277Y is without effect, and all nine mutations of His-127 prevent expression on the cell surface. In the GLIC crystal structure, His-235 on transmembrane (TM) α-helix 2, hydrogen bonds to the main chain carbonyl oxygen of Ile-259 on TM α-helix 3. MD simulations show that when His-235 is protonated, the hydrogen bond persists, and the channel remains in the open conformation, whereas when His-235 is deprotonated, the hydrogen bond dissociates, and the channel closes. Mutations of the proximal Tyr-263, which also links TM α-helices 2 and 3 via a hydrogen bond, alter proton sensitivity over a 1.5 pH unit range. MD simulations show that mutations of Tyr-263 alter the hydrogen bonding capacity of His-235. The overall findings show that His-235 in the TM region of GLIC is a novel proton binding site linked to channel activation. PMID:22084238

  3. [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.

  4. 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.

  5. Modification of LCAT activity and HDL structure. New links between cigarette smoke and coronary heart disease risk.

    PubMed

    McCall, M R; van den Berg, J J; Kuypers, F A; Tribble, D L; Krauss, R M; Knoff, L J; Forte, T M

    1994-02-01

    The mechanism(s) through which smoking influences the progression of atherosclerosis is poorly understood. Recent evidence suggests that oxidants present in the gas phase of cigarette smoke are involved. We exposed human plasma to the filtered gas phase of cigarette smoke to assess its effects on plasma components involved in the antiatherogenic reverse cholesterol transport pathway. In our model, freshly isolated plasma (24 mL) was exposed to filtered air or gas-phase cigarette smoke for up to 6 hours at 37 degrees C. Lecithin-cholesterol acyltransferase (LCAT) activity was dramatically inhibited by cigarette smoke. A single 15-minute exposure to the smoke from an eighth of a cigarette was sufficient to reduce LCAT activity by 7%; additional exposures resulted in further decreases in activity. At 6 hours, only 22% of control LCAT activity remained in plasma exposed to smoke. Compared with control, gas-phase cigarette smoke-exposed plasma possessed high-density lipoprotein (HDL) with increased (16%) negative charge and with cross-linked apolipoproteins AI and AII. These data demonstrate that gas-phase cigarette smoke can inhibit a key enzyme (LCAT) and modify an integral lipid transport particle (HDL) that are essential components for the normal function of the reverse cholesterol transport pathway. Gas-phase cigarette smoke-induced modification of the reverse cholesterol transport pathway may provide a new mechanistic link between cigarette smoke and coronary heart disease risk.

  6. 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.

  7. A biological pathway linking inflammation and depression: activation of indoleamine 2,3-dioxygenase.

    PubMed

    Christmas, David M; Potokar, Jp; Davies, Simon Jc

    2011-01-01

    This article highlights the evidence linking depression to increased inflammatory drive and explores putative mechanisms for the association by reviewing both preclinical and clinical literature. The enzyme indoleamine 2,3-dioxygenase is induced by proinflammatory cytokines and may form a link between immune functioning and altered neurotransmission, which results in depression. Increased indoleamine 2,3-dioxygenase activity may cause both tryptophan depletion and increased neurotoxic metabolites of the kynurenine pathway, two alterations which have been hypothesized to cause depression. The tryptophan-kynurenine pathway is comprehensively described with a focus on the evidence linking metabolite alterations to depression. The use of immune-activated groups at high risk of depression have been used to explore these hypotheses; we focus on the studies involving chronic hepatitis C patients receiving interferon-alpha, an immune activating cytokine. Findings from this work have led to novel strategies for the future development of antidepressants including inhibition of indoleamine 2,3-dioxygenase, moderating the cytokines which activate it, or addressing other targets in the kynurenine pathway.

  8. 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. PMID:12777711

  9. 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

  10. Epigenetic Function of Activation-Induced Cytidine Deaminase and Its Link to Lymphomagenesis

    PubMed Central

    Dominguez, Pilar M.; Shaknovich, Rita

    2014-01-01

    Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation and class switch recombination of immunoglobulin (Ig) genes during B cell maturation and immune response. Expression of AID is tightly regulated due to its mutagenic and recombinogenic potential, which is known to target not only Ig genes, but also non-Ig genes, contributing to lymphomagenesis. In recent years, a new epigenetic function of AID and its link to DNA demethylation came to light in several developmental systems. In this review, we summarize existing evidence linking deamination of unmodified and modified cytidine by AID to base-excision repair and mismatch repair machinery resulting in passive or active removal of DNA methylation mark, with the focus on B cell biology. We also discuss potential contribution of AID-dependent DNA hypomethylation to lymphomagenesis. PMID:25566255

  11. Copper-homoscorpionate complexes as active catalysts for atom transfer radical addition to olefins.

    PubMed

    Muñoz-Molina, José María; Caballero, Ana; Díaz-Requejo, M Mar; Trofimenko, Swiatoslaw; Belderraín, Tomas R; Pérez, Pedro J

    2007-09-17

    Cu(I) complexes containing trispyrazolylborate ligands efficiently catalyze the atom transfer radical addition (ATRA) of polyhalogenated alkanes to various olefins under mild conditions. The catalytic activity is enhanced when bulky and electron donating Tpx ligands are employed. Kinetic data have allowed the proposal of a mechanistic interpretation that includes a Cu(II) pentacoordinated species that regulates the catalytic cycle.

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

    PubMed Central

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

    2001-01-01

    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. PMID:11266322

  13. 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.

  14. 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

  15. Does the Neighborhood Context Alter the Link between Youth's After-School Time Activities and Developmental Outcomes? A Multilevel Analysis

    ERIC Educational Resources Information Center

    Fauth, Rebecca C.; Roth, Jodie L.; Brooks-Gunn, Jeanne

    2007-01-01

    This article examines links between different measures of after-school time activity participation (5 specific activities and breadth) on youth's developmental outcomes (anxiety/depression, delinquency, and substance use) over 6 years and whether these links are moderated by neighborhood-level variables. The sample (N = 1,315) of 9- and…

  16. 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. PMID:25453302

  17. 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.

  18. New evidence for a link between lightning activity and tropical upper cloud coverage

    NASA Astrophysics Data System (ADS)

    Sato, Mitsuteru; Fukunishi, Hiroshi

    2005-06-01

    We report new evidence for a link between lightning activity and tropical upper cloud coverage. Using 1-100 Hz ELF magnetic field waveform data obtained at Syowa station, we analyzed Schumann resonance (SR) spectral intensity variation to investigate characteristics of lightning activity changes. Further, we performed the cross-spectral analysis between the spectral intensity variation and the tropical upper cloud coverage at high altitude derived from infrared cloud images. It is found that the tropical upper cloud coverage and the lightning activity change with the same periodicity and a clear anti-phase relation. These results imply that the lightning activity is closely related to the meteorological dynamics in the troposphere. This fact demonstrates that tropical upper cloud coverage may be continuously monitored by SRs measured at a single site on the Earth's surface.

  19. Insulin and rabbit anti-insulin receptor antibodies stimulate additively the intrinsic receptor kinase activity.

    PubMed Central

    Ponzio, G; Dolais-Kitabgi, J; Louvard, D; Gautier, N; Rossi, B

    1987-01-01

    This paper describes the properties of rabbit polyclonal antibodies directed against purified human insulin receptor which strongly stimulate the intrinsic tyrosine kinase activity. The stimulatory effect of the antibodies on the kinase activity was obtained on the insulin receptor autophosphorylation as well as on the kinase activity towards a synthetic substrate. This stimulation is additive to that induced by insulin. Moreover, rabbit antibodies do not impair insulin binding. These data strongly suggest that antibodies and insulin act through separate pathways. This conclusion is reinforced by the differences observed on the phosphopeptide maps of the receptor's beta subunit whose phosphorylation was performed either in the presence of insulin or rabbit antibodies. Interestingly, these polyclonal antibodies can also induce an activation of the receptor autophosphorylation by interacting only with extracellular determinants. The anti-insulin receptor antibodies mimic insulin in their stimulatory effect on amino acid (AIB) uptake, but they have a different effect to that found on the kinase activity; the simultaneous addition of the antiserum and insulin failed to stimulate this amino acid transport over the level induced by a saturating concentration of hormone. Images Fig. 1. Fig. 3. Fig. 4. Fig. 6. Fig. 7. PMID:3034584

  20. Intramolecular cross-linking of domains at the active site links A1 and B subfragments of the Ca2+-ATPase of sarcoplasmic reticulum.

    PubMed

    Ross, D C; McIntosh, D B

    1987-02-15

    Glutaraldehyde treatment of sarcoplasmic reticulum vesicles results in formation of cross-linked Ca2+-ATPase oligomers. Under limiting reaction conditions, where minimal interpolypeptide cross-linking occurs, hydrodynamic properties of the monomer are altered, such that, on sodium dodecyl sulfate-polyacrylamide electrophoresis, the enzyme migrates with an apparent molecular weight of 125,000 (E(125], as compared to the native enzyme (E(110]. The E(125) species was also formed following reaction with other cross-linking bis-aldehydes, with formaldehyde and with a bissuccinimidyl ester. Derivitization resulted in inactivation of ATPase activity and of phosphoprotein formation from Pi. E(125) formation was inhibited by ATP, ADP, AMPPCP, and orthovanadate, and by specific modification of active site Lys-514 with fluorescein-5'-isothiocyanate. Tryptic cleavage patterns of the glutaraldehyde-modified enzyme were consistent with covalent linkage of A1 and B fragments that have been postulated to comprise the phosphorylation and nucleotide-binding domains (MacLennan, D. H., Brandt, C. J., Korczak, B., and Green, N. M. (1985) Nature 316, 696-700). The denaturing detergent, sodium dodecyl sulfate, prevented cross-link formation. Interdomain cross-linking was inhibited by prior modification with either 2,4,6-trinitrobenzene sulfonate, phenylglyoxal, or pyridoxal-5'-phosphate but was unaffected by thiol group modification with iodoacetate or N-ethylmaleimide, suggesting involvement of lysine residues. These findings indicate that intramolecular cross-linking at the active site of the Ca2+-ATPase involves phosphorylation- and ATP-binding domains that are widely separated in the linear sequence. PMID:2950084

  1. Color removal from cotton textile industry wastewater in an activated sludge system with various additives.

    PubMed

    Pala, Ayşegül; Tokat, Enis

    2002-06-01

    The low biodegradability of many dyes and textile chemicals indicates that biological treatment is not always successful in the treatment of cotton textile wastewater, in terms of color removal. In this study, a specific organic flocculant (Marwichem DEC), powdered activated carbon (PAC), bentonite, activated clay and commercial synthetic inorganic clay (Macrosorb) were directly added into the activated sludge laboratory pilot plant model. Before dosage, the optimum sludge retention time and hydraulic retention time were determined as 30 days and 1.6 days, respectively. The Monod kinetic constants were determined as Y = 0.76 kg MLSS/kg COD, Kd = 0.026 l/day, K(S) = 113.3 mg/L, k = 0.42 l/day and mu(max) = 0.32 kg MLSS/kg COD day. Under these conditions the average COD removal was 94% and color removal was 36%. The addition of these materials did not change COD removal significantly. The most effective materials were found to be DEC and PAC for color removal. While the color removal efficiency for 120 mg/L DEC addition was 78%, it was 65% for 100 mg/L, 77% for 200 mg/L and 86% for 400 mg/L PAC addition. The advantage of DEC compared to PAC was the lower sludge production. Statistical analyses using multiple linear regression indicate that there is no relationship between the effluent color with the influent color and total suspended solids (TSS) for DEC and PAC addition. On the other hand, when only bentonite, activated clay and Macrosorb were added, the effluent color was primarily dependent on the influent color and the TSS concentration had little effect. When the data is examined by using Kruskal-Wallis H and Mann-Whitney U tests and it was found that there was a significant difference between the color data groups.

  2. Spin polarization and additional magneto-optical activity of nonmagnetic layers in Fe/Ag CMF

    NASA Astrophysics Data System (ADS)

    Xu, Y. B.; Zhai, H. R.; Lu, M.; Jin, Q. Y.; Miao, Y. Z.

    1992-08-01

    The experimental magneto-optical Kerr rotation spectra of Fe/Ag compositionally modulated films reported by Katayama et al. are studied theoretically. It is found that the free electrons of Ag are spin polarized. The magnitude of the polarization is about 1% with a direction opposite to that of Fe. The polarized Ag also gives rise to an additional magneto-optical activity as in Pt and Pd.

  3. The PAK system links Rho GTPase signaling to thrombin-mediated platelet activation

    PubMed Central

    Baker, Sandra M.; Loren, Cassandra P.; Haley, Kristina M.; Itakura, Asako; Pang, Jiaqing; Greenberg, Daniel L.; David, Larry L.; Manser, Ed; Chernoff, Jonathan; McCarty, Owen J. T.

    2013-01-01

    Regulation of the platelet actin cytoskeleton by the Rho family of small GTPases is essential for the proper maintenance of hemostasis. However, little is known about how intracellular platelet activation from Rho GTPase family members, including Rac, Cdc42, and Rho, translate into changes in platelet actin structures. To better understand how Rho family GTPases coordinate platelet activation, we identified platelet proteins associated with Rac1, a Rho GTPase family member, and actin regulatory protein essential for platelet hemostatic function. Mass spectrometry analysis revealed that upon platelet activation with thrombin, Rac1 associates with a set of effectors of the p21-activated kinases (PAKs), including GIT1, βPIX, and guanine nucleotide exchange factor GEFH1. Platelet activation by thrombin triggered the PAK-dependent phosphorylation of GIT1, GEFH1, and other PAK effectors, including LIMK1 and Merlin. PAK was also required for the thrombin-mediated activation of the MEK/ERK pathway, Akt, calcium signaling, and phosphatidylserine (PS) exposure. Inhibition of PAK signaling prevented thrombin-induced platelet aggregation and blocked platelet focal adhesion and lamellipodia formation in response to thrombin. Together, these results demonstrate that the PAK signaling system is a key orchestrator of platelet actin dynamics, linking Rho GTPase activation downstream of thrombin stimulation to PAK effector function, MAP kinase activation, calcium signaling, and PS exposure in platelets. PMID:23784547

  4. Activation of lactoperoxidase by heme-linked protonation and heme-independent iodide binding.

    PubMed

    Toyama, Akira; Tominaga, Aya; Inoue, Tatsuo; Takeuchi, Hideo

    2010-01-01

    Lactoperoxidase (LPO), a mammalian secretory heme peroxidase, catalyzes the oxidation of thiocyanate by hydrogen peroxide to produce hypothiocyanate, an antibacterial agent. Although LPO is known to be activated at acidic pH and in the presence of iodide, the structural basis of the activation is not well understood. We have examined the effects of pH and iodide concentration on the catalytic activity and the structure of LPO. Electrochemical and colorimetric assays have shown that the catalytic activity is maximized at pH 4.5. The heme Soret absorption band exhibits a small red-shift at pH 5.0 upon acidification, which is ascribable to a structural transition from a neutral to an acidic form. Resonance Raman spectra suggest that the heme porphyrin core is slightly contracted and the Fe-His bond is strengthened in the acidic form compared to the neutral form. The structural change of LPO upon activation at acidic pH is similar to that observed for myeloperoxidase, another mammalian heme peroxidase, upon activation at neutral pH. Binding of iodide enhances the catalytic activity of LPO without affecting either the optimum pH of activity or the heme structure, implying that the iodide binding occurs at a protein site away from the heme-linked protonation site.

  5. 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.

  6. 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.

  7. 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; Debe, Mark; Steinbach, Andrew J.; Guetaz, L.

    2015-04-10

    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

  8. 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.

    2015-04-10

    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.

  9. 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.

  10. 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. PMID:26342545

  11. 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.

  12. Caught in the act: covalent cross-linking captures activator-coactivator interactions in vivo.

    PubMed

    Krishnamurthy, Malathy; Dugan, Amanda; Nwokoye, Adaora; Fung, Yik-Hong; Lancia, Jody K; Majmudar, Chinmay Y; Mapp, Anna K

    2011-12-16

    Currently there are few methods suitable for the discovery and characterization of transient, moderate affinity protein-protein interactions in their native environment, despite their prominent role in a host of cellular functions including protein folding, signal transduction, and transcriptional activation. Here we demonstrate that a genetically encoded photoactivatable amino acid, p-benzoyl-l-phenylalanine, can be used to capture transient and/or low affinity binding partners in an in vivo setting. In this study, we focused on ensnaring the coactivator binding partners of the transcriptional activator VP16 in S. cerevisiae. The interactions between transcriptional activators and coactivators in eukaryotes are moderate in affinity and short-lived, and due in part to these characteristics, identification of the direct binding partners of activators in vivo has met with only limited success. We find through in vivo photo-cross-linking that VP16 contacts the Swi/Snf chromatin-remodeling complex through the ATPase Snf2(BRG1/BRM) and the subunit Snf5 with two distinct regions of the activation domain. An analogous experiment with Gal4 reveals that Snf2 is also a target of this activator. These results suggest that Snf2 may be a valuable target for small molecule probe discovery given the prominent role the Swi/Snf complex family plays in development and in disease. More significantly, the successful implementation of the in vivo cross-linking methodology in this setting demonstrates that it can be applied to the discovery and characterization of a broad range of transient and/or modest affinity protein-protein interactions. PMID:21977905

  13. Synthesis and antimicrobial activity of some novel cross-linked chitosan hydrogels.

    PubMed

    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

  14. 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

  15. Synthesis and antimicrobial activity of some novel cross-linked chitosan hydrogels.

    PubMed

    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.

  16. 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

  17. Characterization of the Enzymatic Activity of the Actin Cross-Linking Domain from the Vibrio cholerae MARTXVc Toxin

    PubMed Central

    Kudryashov, Dmitri S.; Cordero, Christina L.; Reisler, Emil; Fullner Satchell, Karla J.

    2008-01-01

    Vibrio cholerae is a Gram-negative bacterial pathogen that exports enterotoxins which alter host cells through a number of mechanisms resulting in diarrheal disease. Among the secreted toxins is the multifunctional, autoprocessing RTX toxin (MARTXVc), which disrupts actin cytoskeleton by covalently cross-linking actin monomers into oligomers. The region of the toxin responsible for cross-linking activity is the actin cross-linking domain (ACD). In this study, we demonstrate unambiguously that ACD utilizes G- and not F-actin as a substrate for the cross-linking reaction and hydrolyzes one molecule of ATP per cross-linking event. Furthermore, major actin binding proteins that regulate actin cytoskeleton in vivo do not block the cross-linking reaction in vitro. Cofilin inhibits the cross-linking of G- and F-actin at high mole ratio to actin, but accelerates F-actin cross-linking at low mole ratios. DNase I blocks completely the cross-linking of actin, likely due to steric hindrance with one of the cross-linking sites on actin. In the context of the holotoxin, the inhibition of Rho by the Rho-inactivating domain of MARTXVc (Sheahan, K.L., Satchell, K.J.F. 2007 Cellular Microbiology 9:1324-1335) would accelerate F-actin depolymerization and provide G-actin, alone or in complex with actin binding proteins, for cross-linking by ACD, ultimately leading to the observed rapid cell rounding. PMID:17951576

  18. 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

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

    PubMed

    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 reactive

  20. Enhancement of anammox activity by addition of compatible solutes at high salinity conditions.

    PubMed

    Liu, Mu; Peng, Yongzhen; Wang, Shuying; Liu, Tiantian; Xiao, Han

    2014-09-01

    The enhancement effect of compatible solutes on anammox activity under salinity stress was investigated. Glycine betaine (GB) was the most effective in alleviating salt toxicity, although all the compatible solutes (GB, trehalose and ectoine) were found to be valid. Acclimation potential of anammox biomass under salinity of 30 g/L increased significantly with GB addition. The recovery time in the reactor with GB addition (RB) (49 days) accompanied by a more stable stoichiometric ratio was 2.65 times shorter than in the control reactor (RC) (130 days). After 49 days, the extracellular polymeric substances and the tetrazolium chloride-dehydrogenase activity were 217.9 mg/g VSS and 38.7 μg TF/g VSS/h in RB, 1.86 times lower and 3.17 times higher than the levels in RC, respectively. RB possessed evident superiority in the aspects of microbial population proportion. And thus, compatible solutes addition was regarded as one of the feasible solution to counteract saline inhibition on anammox. PMID:25024098

  1. 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.

  2. 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.

  3. 77 FR 67655 - Agency Information Collection Activities; Proposed Collection; Comment Request; Food Additive...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-13

    ... Collection; Comment Request; Food Additive Petitions and Investigational Food Additive Exemptions; Extension... comment in response to the notice. This notice solicits comments on food additive petitions regarding... of information technology. Food Additive Petitions and Investigational Food Additive Exemptions,...

  4. Controlling a toxic shock of pentachlorophenol (PCP) to anaerobic digestion using activated carbon addition.

    PubMed

    Xiao, Yeyuan; De Araujo, Cecilia; Sze, Chun Chau; Stuckey, David C

    2015-04-01

    Several powdered and granular activated carbons (PACs and GACs) were tested for adsorption of pentachlorophenol (PCP) in bench-scale anaerobic digestion reactors to control the toxicity of PCP to acetoclastic methanogenesis. Results showed that the adsorption capacities of PAC were reduced by 21-54%, depending on the PAC addition time, in the presence of the methanogenic sludge compared to the controls without sludge. As a preventive measure, PAC at a low dose of 20% (mass ratio to the VSS) added 24 h prior to, or simultaneously with, the addition of PCP could completely eliminate the toxic effects of PCP. At the same dose, PAC also enabled methanogenesis to recover immediately after the sludge had been exposed to PCP for 24h. GAC was not effective in enabling the recovery of methanogenesis due to its slow adsorption kinetics; however, at a dose of 80% it could partially ameliorate the toxic shock of PCP. PMID:25665874

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. VAMP-7 links granule exocytosis to actin reorganization during platelet activation.

    PubMed

    Koseoglu, Secil; Peters, Christian G; Fitch-Tewfik, Jennifer L; Aisiku, Omozuanvbo; Danglot, Lydia; Galli, Thierry; Flaumenhaft, Robert

    2015-07-30

    Platelet activation results in profound morphologic changes accompanied by release of granule contents. Recent evidence indicates that fusion of granules with the plasma membrane during activation provides auxiliary membrane to cover growing actin structures. Yet little is known about how membrane fusion is coupled with actin reorganization. Vesicle-associated membrane protein (VAMP)-7 is found on platelet vesicles and possesses an N-terminal longin domain capable of linking exocytosis to cytoskeletal remodeling. We have evaluated platelets from VAMP-7(-/-) mice to determine whether this VAMP isoform contributes to granule release and platelet spreading. VAMP-7(-/-) platelets demonstrated a partial defect in dense granule exocytosis and impaired aggregation. α Granule exocytosis from VAMP-7(-/-) platelets was diminished both in vitro and in vivo during thrombus formation. Consistent with a role of VAMP-7 in cytoskeletal remodeling, spreading on matrices was decreased in VAMP-7(-/-) platelets compared to wild-type controls. Immunoprecipitation of VAMP-7 revealed an association with VPS9-domain ankyrin repeat protein (VARP), an adaptor protein that interacts with both membrane-bound and cytoskeleton proteins and with Arp2/3. VAMP-7, VARP, and Arp2/3 localized to the platelet periphery during spreading. These studies demonstrate that VAMP-7 participates in both platelet granule secretion and spreading and suggest a mechanism whereby VAMP-7 links granule exocytosis with actin reorganization. PMID:25999457

  10. VAMP-7 links granule exocytosis to actin reorganization during platelet activation.

    PubMed

    Koseoglu, Secil; Peters, Christian G; Fitch-Tewfik, Jennifer L; Aisiku, Omozuanvbo; Danglot, Lydia; Galli, Thierry; Flaumenhaft, Robert

    2015-07-30

    Platelet activation results in profound morphologic changes accompanied by release of granule contents. Recent evidence indicates that fusion of granules with the plasma membrane during activation provides auxiliary membrane to cover growing actin structures. Yet little is known about how membrane fusion is coupled with actin reorganization. Vesicle-associated membrane protein (VAMP)-7 is found on platelet vesicles and possesses an N-terminal longin domain capable of linking exocytosis to cytoskeletal remodeling. We have evaluated platelets from VAMP-7(-/-) mice to determine whether this VAMP isoform contributes to granule release and platelet spreading. VAMP-7(-/-) platelets demonstrated a partial defect in dense granule exocytosis and impaired aggregation. α Granule exocytosis from VAMP-7(-/-) platelets was diminished both in vitro and in vivo during thrombus formation. Consistent with a role of VAMP-7 in cytoskeletal remodeling, spreading on matrices was decreased in VAMP-7(-/-) platelets compared to wild-type controls. Immunoprecipitation of VAMP-7 revealed an association with VPS9-domain ankyrin repeat protein (VARP), an adaptor protein that interacts with both membrane-bound and cytoskeleton proteins and with Arp2/3. VAMP-7, VARP, and Arp2/3 localized to the platelet periphery during spreading. These studies demonstrate that VAMP-7 participates in both platelet granule secretion and spreading and suggest a mechanism whereby VAMP-7 links granule exocytosis with actin reorganization.

  11. VAMP-7 links granule exocytosis to actin reorganization during platelet activation

    PubMed Central

    Koseoglu, Secil; Peters, Christian G.; Fitch-Tewfik, Jennifer L.; Aisiku, Omozuanvbo; Danglot, Lydia; Galli, Thierry

    2015-01-01

    Platelet activation results in profound morphologic changes accompanied by release of granule contents. Recent evidence indicates that fusion of granules with the plasma membrane during activation provides auxiliary membrane to cover growing actin structures. Yet little is known about how membrane fusion is coupled with actin reorganization. Vesicle-associated membrane protein (VAMP)-7 is found on platelet vesicles and possesses an N-terminal longin domain capable of linking exocytosis to cytoskeletal remodeling. We have evaluated platelets from VAMP-7−/− mice to determine whether this VAMP isoform contributes to granule release and platelet spreading. VAMP-7−/− platelets demonstrated a partial defect in dense granule exocytosis and impaired aggregation. α Granule exocytosis from VAMP-7−/− platelets was diminished both in vitro and in vivo during thrombus formation. Consistent with a role of VAMP-7 in cytoskeletal remodeling, spreading on matrices was decreased in VAMP-7−/− platelets compared to wild-type controls. Immunoprecipitation of VAMP-7 revealed an association with VPS9-domain ankyrin repeat protein (VARP), an adaptor protein that interacts with both membrane-bound and cytoskeleton proteins and with Arp2/3. VAMP-7, VARP, and Arp2/3 localized to the platelet periphery during spreading. These studies demonstrate that VAMP-7 participates in both platelet granule secretion and spreading and suggest a mechanism whereby VAMP-7 links granule exocytosis with actin reorganization. PMID:25999457

  12. Thylakoid Membrane Maturation and PSII Activation Are Linked in Greening Synechocystis sp. PCC 6803 Cells1

    PubMed Central

    Barthel, Sandra; Bernát, Gábor; Seidel, Tobias; Rupprecht, Eva; Kahmann, Uwe; Schneider, Dirk

    2013-01-01

    Thylakoid membranes are typical and essential features of both chloroplasts and cyanobacteria. While they are crucial for phototrophic growth of cyanobacterial cells, biogenesis of thylakoid membranes is not well understood yet. Dark-grown Synechocystis sp. PCC 6803 cells contain only rudimentary thylakoid membranes but still a relatively high amount of phycobilisomes, inactive photosystem II and active photosystem I centers. After shifting dark-grown Synechocystis sp. PCC 6803 cells into the light, “greening” of Synechocystis sp. PCC 6803 cells, i.e. thylakoid membrane formation and recovery of photosynthetic electron transport reactions, was monitored. Complete restoration of a typical thylakoid membrane system was observed within 24 hours after an initial lag phase of 6 to 8 hours. Furthermore, activation of photosystem II complexes and restoration of a functional photosynthetic electron transport chain appears to be linked to the biogenesis of organized thylakoid membrane pairs. PMID:23922268

  13. Activation-Induced Cytidine Deaminase Links Ovulation-Induced Inflammation and Serous Carcinogenesis.

    PubMed

    Sapoznik, Stav; Bahar-Shany, Keren; Brand, Hadar; Pinto, Yishay; Gabay, Orshay; Glick-Saar, Efrat; Dor, Chen; Zadok, Oranit; Barshack, Iris; Zundelevich, Adi; Gal-Yam, Einav Nili; Yung, Yuval; Hourvitz, Ariel; Korach, Jacob; Beiner, Mario; Jacob, Jasmine; Levanon, Erez Y; Barak, Michal; Aviel-Ronen, Sarit; Levanon, Keren

    2016-02-01

    In recent years, the notion that ovarian carcinoma results from ovulation-induced inflammation of the fallopian tube epithelial cells (FTECs) has gained evidence. However, the mechanistic pathway for this process has not been revealed yet. In the current study, we propose the mutator protein activation-induced cytidine deaminase (AID) as a link between ovulation-induced inflammation in FTECs and genotoxic damage leading to ovarian carcinogenesis. We show that AID, previously shown to be functional only in B lymphocytes, is expressed in FTECs under physiological conditions, and is induced in vitro upon ovulatory-like stimulation and in vivo in carcinoma-associated FTECs. We also report that AID activity results in epigenetic, genetic and genomic damage in FTECs. Overall, our data provides new insights into the etiology of ovarian carcinogenesis and may set the ground for innovative approaches aimed at prevention and early detection. PMID:26936395

  14. Catalytic cracking of vacuum gasoil in the presence of activating additives

    SciTech Connect

    Abdul'menov, R.G.; Serikov, P.Y.; Smidovich, E.V.; Syunyaev, Z.I.

    1985-07-01

    These authors perform catalytic cracking of vacuum gas oil in a singlepass laboratory flow unit with mechanized mixing of a bed of the microbead zeolitic catalyst KMTsR. They present data in a series of three tables and in a set of three charts. Analysis of these data leads them to conclude that the use of activating additives makes it possible to reduce the coke yield and bring coke deposition down to a preassigned level. They further conclude that their method for intensifying catalytic cracking is especially promising for heavy types of feed with high carbon residues.

  15. 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. PMID:23612160

  16. 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

  17. Spontaneous regional brain activity links restrained eating to later weight gain among young women.

    PubMed

    Dong, Debo; Jackson, Todd; Wang, Yulin; Chen, Hong

    2015-07-01

    Theory and prospective studies have linked restrained eating (RE) to risk for future weight gain and the onset of obesity, but little is known about resting state neural activity that may underlie this association. To address this gap, resting fMRI was used to test the extent to which spontaneous neural activity in regions associated with inhibitory control and food reward account for potential relations between baseline RE levels and changes in body weight among dieters over a one-year interval. Spontaneous regional activity patterns corresponding to RE were assessed among 50 young women using regional homogeneity (ReHo) analysis, which measured temporal synchronization of spontaneous fluctuations within a food deprivation condition. Analyses indicated higher baseline RE scores predicted more weight gain at a one-year follow-up. Furthermore, food-deprived dieting women with high dietary restraint scores exhibited more spontaneous local activity in brain regions associated with the expectation and valuation for food reward [i.e., orbitofrontal cortex (OFC)/ventromedial prefrontal cortex (VMPFC)] and reduced spontaneous local activity in inhibitory control regions [i.e., bilateral dorsal-lateral prefrontal cortex (DLPFC)] at baseline. Notably, the association between baseline RE and follow-up weight gain was mediated by decreased local synchronization of the right DLPFC in particular and, to a lesser degree, increased local synchronization of the right VMPFC. In conjunction with previous research, these findings highlight possible neural mechanisms underlying the relation between RE and risk for weight gain. PMID:26004091

  18. Spontaneous regional brain activity links restrained eating to later weight gain among young women.

    PubMed

    Dong, Debo; Jackson, Todd; Wang, Yulin; Chen, Hong

    2015-07-01

    Theory and prospective studies have linked restrained eating (RE) to risk for future weight gain and the onset of obesity, but little is known about resting state neural activity that may underlie this association. To address this gap, resting fMRI was used to test the extent to which spontaneous neural activity in regions associated with inhibitory control and food reward account for potential relations between baseline RE levels and changes in body weight among dieters over a one-year interval. Spontaneous regional activity patterns corresponding to RE were assessed among 50 young women using regional homogeneity (ReHo) analysis, which measured temporal synchronization of spontaneous fluctuations within a food deprivation condition. Analyses indicated higher baseline RE scores predicted more weight gain at a one-year follow-up. Furthermore, food-deprived dieting women with high dietary restraint scores exhibited more spontaneous local activity in brain regions associated with the expectation and valuation for food reward [i.e., orbitofrontal cortex (OFC)/ventromedial prefrontal cortex (VMPFC)] and reduced spontaneous local activity in inhibitory control regions [i.e., bilateral dorsal-lateral prefrontal cortex (DLPFC)] at baseline. Notably, the association between baseline RE and follow-up weight gain was mediated by decreased local synchronization of the right DLPFC in particular and, to a lesser degree, increased local synchronization of the right VMPFC. In conjunction with previous research, these findings highlight possible neural mechanisms underlying the relation between RE and risk for weight gain.

  19. 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.

  20. 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

  1. 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.

  2. 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. PMID:27253271

  3. Cross-linking of structural proteins in ageing skin: an in situ assay for the detection of amine oxidase activity.

    PubMed

    Langton, Abigail K; Griffiths, Christopher E M; Sherratt, Michael J; Watson, Rachel E B

    2013-02-01

    With increasing age, dynamic tissues such as lungs, blood vessels and skin lose their ability to both deform and recoil, culminating in tissue stiffening. This loss of tissue elasticity, which profoundly impacts tissue function and thus morbidity, may be due not only to changes in the relative abundance of key extracellular matrix proteins within tissues but also to their accumulation of post-translational modifications. Whilst to date attention has focussed primarily on the age-related non-enzymatic formation of advanced glycation end products, the accumulation of pathological enzyme-mediated cross-links may also lead to age-related tissue stiffening. The lysyl oxidase (LOX) family of enzymes are constitutively expressed in adult tissues and are known to drive the catalysis of cross-links in both fibrillar collagens and elastin. Although immunochemical approaches are commonly used to localise the inactive pro-enzyme of LOX, and biochemical methods are employed to quantify activity in homogenised tissue, they do not allow for the in situ localisation of the enzyme. Thus, we have developed a novel assay to both detect and localise LOX enzyme activity in situ. LOX family members are amine oxidases and this assay uses the principle that an amine substrate in the presence of this class of enzyme will be oxidised to an aldehyde and hydrogen peroxide (H2O2). In turn, H2O2, when combined with luminol and horseradish peroxidase, will produce a light-emitting reaction that can be detected by film autoradiography. The development of a technique to localise specific amine oxidase activity in tissue sections may provide crucial additional information on the exact role played by this class of enzymes in mediating age-related tissue stiffening.

  4. 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

  5. Flux enhancement with powdered activated carbon addition in the membrane anaerobic bioreactor

    SciTech Connect

    Park, H.; Choo, K.H.; Lee, C.H.

    1999-10-01

    The effect of powdered activated carbon (PAC) addition on the performance of a membrane-coupled anaerobic bioreactor (MCAB) was investigated in terms of membrane filterability and treatability through a series of batch and continuous microfiltration (MF) experiments. In both batch and continuous MF of the digestion broth, a flux improvement with PAC addition was achieved, especially when a higher shear rate and/or a higher PAC dose were applied. Both the fouling and cake layer resistances decreased continuously with increasing the PAC dose up to 5 g/L. PAC played an important role in substantially reducing the biomass cake resistance due to its incompressible nature and higher backtransport velocities. PAC might have a scouring effect for removing the deposited biomass cake from the membrane surface while sorbing and/or coagulating dissolved organics and colloidal particles in the broth. The chemical oxygen demand and color in the effluent were much removed with PAC addition, and the system was also more stable against shock loading.

  6. 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.

  7. Enhanced esterification activity through interfacial activation and cross-linked immobilization mechanism of Rhizopus oryzae lipase in a nonaqueous medium.

    PubMed

    Kartal, Funda

    2016-07-01

    Interfacial activation via surfactant (Tween 80, Triton X-100) treatment was conducted to improve the esterification activity of Rhizopus oryzae lipase that had undergone immobilization through cross-linked enzyme aggregates (CLEA®) technique. Surfactant pretreated immobilized enzymes exhibited better esterification activity compared to free and non-pretreated immobilized enzyme (Control CLEAs) since higher conversion rates were obtained within shorter times. The superiority of surfactant pretreated CLEAs, especially Tween 80 pretreated CLEAs (T 80 PT CLEAs), were clearly pronounced when longer alcohols were used as substrates. Conversion values exceeded 90% for octyl octanoate, oleyl octanoate and oleyl oleate synthesis with T 80 PT CLEAs whereas Control CLEAs and free enzyme showed no activity. Maximum conversions were achieved in the case equal molars of the substrates or in the case excess of the alcohol to acid in cyclohexane. In solvent free medium containing equal molars of substrates the conversion rates were 85% and 87% with T 80 PT CLEAs respectively for octyl octanoate and oleyl oleate within 2 hours. T 80 PT CLEAs showed 59% of its original activity after 7 consecutive usage for oleyl oleate synthesis. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:899-904, 2016. PMID:27111483

  8. Intracellular pathways linking hypoxia to activation of c-fos and AP-1.

    PubMed

    Premkumar, D R; Adhikary, G; Overholt, J L; Simonson, M S; Cherniack, N S; Prabhakar, N R

    2000-01-01

    Organisms respond to hypoxia through detection of blood oxygen levels by sensors at peripheral chemoreceptors and by receptors in certain key cells of the body. The pathways over which peripheral chemoreceptor signals are transmitted to respiratory muscles are well established. However, the intracellular pathways that transmit hypoxic stimulus to gene activation are just being identified. Using anti-sense c-fos strategy, we have shown that c-fos is essential for the activation of activator protein-1 transcription factor complex (AP-1) and subsequent stimulation of downstream genes such as tyrosine hydroxylase (TH; Mishra et al. 1998). The purpose of the present study was to identify intracellular pathways that link hypoxia to activation of c-fos. The results of the present study show that hypoxia causes Ca2+ influx through L-type voltage gated Ca2+ channels and that hypoxia-induced c-fos gene expression is Ca2+/calmodulin dependent. We also demonstrate that hypoxia activates the extracellular-regulated kinase (ERK) and p38, but not JNK. Further, phosphorylation of ERK is essential for c-fos activation via SRE cis-element. Further characterization of nuclear signalling pathways provides evidence for the involvement of Src, a non receptor protein tyrosine kinase, and Ras, a small G protein, in the hypoxia-induced c-fos gene expression. These results suggest a possible role for non-receptor protein tyrosine kinases in propagating signals from G-protein coupled receptors to the activation of immediate early genes such as c-fos during hypoxia.

  9. Thermal formation of PBDD/F from tetrabromobisphenol A--a comparison of polymer linked TBBP A with its additive incorporation in thermoplastics.

    PubMed

    Wichmann, H; Dettmer, F T; Bahadir, M

    2002-04-01

    For a long period, polybrominated flame retardants are under discussion because of the formation of polybrominated dibenzo-p-dioxins (PBDD)/dibenzofurans (PBDF) (PBDD/F) in case of thermal stress. Concerning polymer linked tetrabromobisphenol A (TBBP A), formation of PBDD/F was commonly presumed to be sterically hindered because of the covalent fixation into the polymer backbone. Combustion experiments with additively incorporated TBBP A compared with its polymer linkage revealed, that this assumption is incorrect and has to be revised. Under same conditions, similar PBDD/F concentrations in the range of 17.5-19.6 mg PBBD/F per kg TBBP A applied were analyzed. PBDD/F homologue distribution patterns were almost identical predominated by low brominated PBDF. These findings for PBDD/F formation have to be considered in future discussions regarding thermal stress caused by combustion or recycling processes, including other flame retardants bound in polymer matrix, e.g. polybrominated polystyrene (PS), or those with molecular structures showing less analogy to PBDD/F, like hexabromocyclododecane. The second aspect introduced, is the influence of different plastics on the formation rates of PBDD/F. In this context, combustion experiments were performed in an atmosphere consisting of synthetic air and HBr. PBDD/F concentrations were 8.47 mg/kg polyethylene, 1.67 mg/kg PS, 3.92 mg/kg phenolic resin and 18.1 mg/kg epoxy resin. Distribution patterns of PBDD/F homologues could partly be correlated with the occurrence of the precursors polybrominated benzenes and phenols.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. Temporal link between plasma thyrotropin levels and electroencephalographic activity in man.

    PubMed

    Gronfier, C; Luthringer, R; Follenius, M; Schaltenbrand, N; Macher, J P; Muzet, A; Brandenberger, G

    1995-11-17

    Plasma thyrotropin (TSH) levels have been previously shown to be associated with the internal sleep structure determined by conventional scoring of sleep stages. This temporal relationship was re-evaluated using spectral analysis of the sleep electroencephalogram (EEG). Eight healthy male subjects underwent two randomized night studies after having received either placebo or 5 mg ritanserin, a selective 5-HT2 receptor antagonist known to increase slow-wave sleep. Delta relative power and TSH levels, determined at 10 min intervals, were found to be inversely related with an average cross-correlation coefficient highly significant (P < 0.0001) in both experimental conditions. Alpha slow-wave index, an estimator of awakenings, and TSH pulses exhibited a significant temporal association in both conditions. These results demonstrate that TSH fluctuations are linked to the sleep EEG activity in man.

  16. Simple route to enhanced photocatalytic activity of p25 titanium dioxide nanoparticles by silica addition.

    PubMed

    Jafry, Huma R; Liga, Michael V; Li, Qilin; Barron, Andrew R

    2011-02-15

    Silica doped TiO2(P25) nanoparticles are tested for its photocatalytic activity in the degradation of bacteriophage MS2. During our studies it was found that treatment of TiO2(P25) in the glass flasks sealed with silicone grease resulted in a significant improvement in the catalytic activity of the titania. Further improvement can be made by the purposeful reaction of TiO2(P25) with 2.5 wt % silica. This non in situ method of incorporating silica to TiO2(P25) nanoparticles is tested for their role in killing of viruses, and it is found that the rate constant is three times higher to kill viruses with the addition of silica. BET measurements show no significant change/increase in the surface area of silica doped TiO2(P25)-SiO2, compared to the undoped TiO2(P25). Further studies show that the addition of silica increases the adsorption of viruses onto the catalyst. There is a significant difference in the activity of the TiO2(P25)-SiO2 samples in the presence of methanol, supporting the notion that hydroxide radical (HO·) is responsible for the antiviral action. The TiO2(P25)-SiO2 either produces more HO· than non silica-doped material, or the enhanced adsorption of MS2 to the catalyst results in greater exposure to the HO·, or both mechanisms may work in concert. XPS studies suggest the formation of silica species on the surface of the TiO2(P25), while UV-visible spectroscopy suggests that the presence of the silica results in a small increase in the measured band gap. We suggest that the enhanced catalytic activity is a result of increased adsorption and/or band bending which can occur at the interface within TiO2(P25)-SiO2. One result of this would be a reduction of the electron-hole recombination, the formation of a greater concentration of OH·, and hence an improved catalytic performance.

  17. 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.

  18. Speed of mental addition in an abacus expert, estimated by eye movements and neural activities.

    PubMed

    Hamada, Takashi; Iwaki, Sunao

    2012-08-01

    A grand expert of abacus looked at a display on which three-digit numbers were aligned vertically with constant spacing, for sequentially adding the numbers mentally. His eye regularly moved downward by alternating a fixation to one of the numbers with a saccade to another below it, with the average period of the alternations at 271 msec. His magnetoencephalogram averaged with respect to start of the fixations revealed activity in the right superior parietal cortex. This finding not only supported the previous view that abacus experts mentally calculate by manipulating spatial representations of numbers, but also showed that the calculation was synchronized with the periodic eye movements. Thus, each process of the mental sequential addition, which starts with visual recognition of an addend, was estimated to require less than 271 msec. on average.

  19. Active Contours Using Additive Local and Global Intensity Fitting Models for Intensity Inhomogeneous Image Segmentation

    PubMed Central

    Soomro, Shafiullah; Kim, Jeong Heon; Soomro, Toufique Ahmed

    2016-01-01

    This paper introduces an improved region based active contour method with a level set formulation. The proposed energy functional integrates both local and global intensity fitting terms in an additive formulation. Local intensity fitting term influences local force to pull the contour and confine it to object boundaries. In turn, the global intensity fitting term drives the movement of contour at a distance from the object boundaries. The global intensity term is based on the global division algorithm, which can better capture intensity information of an image than Chan-Vese (CV) model. Both local and global terms are mutually assimilated to construct an energy function based on a level set formulation to segment images with intensity inhomogeneity. Experimental results show that the proposed method performs better both qualitatively and quantitatively compared to other state-of-the-art-methods. PMID:27800011

  20. 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. PMID:26906712

  1. Improvement of a sensitive enzyme-linked immunosorbent assay for screening estrogen receptor binding activity.

    PubMed

    Koda, Tomoko; Soya, Yoshihiro; Negishi, Harumi; Shiraishi, Fujio; Morita, Masatoshi

    2002-12-01

    A competitive enzyme-linked immunosorbent assay (ELISA) with estrogen receptor (alpha) and a fluorescence depolarization method with Full-Range Beacon were examined as estrogen receptor binding assays to prescreen endocrine-disrupting chemicals (EDCs). In this study, because it is difficult to measure the receptor binding ability of sparingly water-soluble chemicals using these methods, the competitive enzyme immunoassay was further modified for improved sensitivity by changing the operational parameters, such as receptor concentration, ligand concentration, and the reaction temperature. The method was applied to 10 test chemicals, including alkylphenols and bisphenol A (BPA). The diethylstilbestrol (DES) relative binding affinity (RBA) of ELISA kit was set equal to 1 (RBA = IC50/IC50 of DES). The RBAs of BPA, 4-nonylphenol (p-NP), and 4-t-octylphenol (p-t-OP) are 5386, 8619. and 8121 before using the improved competitive enzyme immunoassay and 883, 699, and 2832 using improved it respectively. Mixtures of BPA, p-NP, and p-t-OP gave results that the estrogen binding affinities of these chemicals are additive or slightly more than additive.

  2. Integrin-linked kinase activity modulates the pro-metastatic behavior of ovarian cancer cells

    PubMed Central

    Bruney, Lana; Liu, Yueying; Grisoli, Anne; Ravosa, Matthew J.; Stack, M. Sharon

    2016-01-01

    Epithelial ovarian cancer (EOC) is the most fatal gynecologic cancer in the U.S., resulting in >14,000 deaths/year. Most women are diagnosed at late stage with widely disseminated intra-peritoneal metastatic disease, resulting in a 5-year survival rate of <30%. EOCs spread via direct extension and exfoliation into the peritoneal cavity, adhesion to peritoneal mesothelial cells, mesothelial cell retraction to expose sub-mseothelial matrix and anchoring in the type I collagen-rich matrix to generate secondary lesions. As a molecular-level understanding of EOC metastasis may identify novel therapeutic targets, the current study evaluated the expression and activity of integrin-linked kinase (ILK), a Ser/Thr protein kinase activated upon integrin-mediated adhesion. Results show that ILK is co-expressed in EOC with the pro-metastatic enzyme membrane type 1 matrix metalloproteinase (MT1-MMP) and catalyzed phosphorylation of the cytoplasmic tail of the proteinase. Downregulation of ILK expression or activity reduced adhesion to and invasion of collagen gels and organotypic meso-mimetic cultures. As an initial early event in EOC metastasis is integrin-mediated adhesion, these results suggest that further evaluation of ILK inhibitors as anti-metastatic agents in EOC is warranted. PMID:26959113

  3. Linking nutrition and behavioural dominance: carbohydrate scarcity limits aggression and activity in Argentine ants.

    PubMed

    Grover, Crystal D; Kay, Adam D; Monson, Jessica A; Marsh, Thomas C; Holway, David A

    2007-12-01

    Predicting the outcome of competitive interactions is a fundamental goal in ecology. Ecological stoichiometry, which relates nutrient balance to ecological processes, provides a framework for identifying mechanistic links among macronutrient availability, nutritional physiology and competitive performance. Because carbohydrates serve as a principal metabolic fuel, carbohydrate scarcity may impinge upon behaviours affecting competitive dominance (e.g. aggression, activity) to a greater extent than deficiencies of protein or other nutrients used preferentially for growth. Here, we tested this prediction with a diet manipulation study involving laboratory colonies of Argentine ants (Linepithema humile), a widespread and aggressive invasive species. The availability of both sucrose and insect prey influenced brood production and worker survival after three months. However, colonies became less aggressive and less active only when deprived of sucrose (but not prey). Scarcity of sucrose (but not prey) was also associated with reduced fat mass in individual workers. These data provide the first experimental support that carbohydrate scarcity compromises aggression and activity in ants, and illustrate, in principle, how access to carbohydrate-rich resources (e.g. plant exudates, hemipteran honeydew) might influence behavioural investments that contribute to competitive performance. Such investments might be especially important for invasive ants, given their aggressiveness and tendency to interact with honeydew-producing Hemiptera.

  4. Subchronic exposure to leachate activates key markers linked with neurological disorder in Wistar male rat.

    PubMed

    Akintunde, J K; Oboh, G

    2015-12-01

    The linking of various environmental chemicals exposure to neurodegenerative disorders is current. This study was undertaken to elucidate the toxic effects and the underlying biochemical mechanism of leachate obtained from Elewi Odo municipal battery recycling site (EOMABRL) using key markers of neuronal damage in rat via an oral route. Analysis of the concentrations of heavy metals showed that lead, cadmium, nickel, chromium, manganese, and iron were higher than the acceptable limits set by the regulatory authority-the World Health Organization. Whereas, copper, zinc, and cobalt were lower than permissible limits. EOMABRL was administered at 0, 20, 40, 60, 80, and 100% concentrations to adult male rats for 60 days. An in vitro study was also carried out in the cerebellum to assess cholinesterase biochemistry assays. Following exposure, brain was collected to determine the antioxidant status. EOMABRL administration significantly increased superoxide dismutase (SOD) and catalase (CAT) activities, and a sequential decrease in reduced glutathione (GSH) level with a concomitant increase in the accumulation of hydrogen peroxide (H2O2) and malondialdehyde (MDA) level was observed, when compared with the control. The treated rat had a significant (P < 0.05) increase in the activities of acetycholinesterase (AChE) and butyrylcholinesterase (BuChE). Taken together, these findings conclude that some possible mechanisms by which EOMABRL elicits neuronal disorder in male rat could be through the activation of AChE and BuChE and induction of oxidative stress with necrosis of neuronal cells. PMID:26362636

  5. 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. PMID:24657762

  6. 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.

  7. Lorenzo's oil and platelet activation in adrenomyeloneuropathy and asymptomatic X-linked adrenoleukodystrophy.

    PubMed

    Konijnenberg, A; van Geel, B M; Sturk, A; Schaap, M C; von dem Borne, A E; de Bruijne-Admiraal, L G; Schutgens, R B; Assies, J; Barth, P G

    1998-01-01

    X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder of peroxisomal beta-oxidation, which results in accumulation of very long-chain fatty acids, causing damage to the nervous system, adrenal cortex and testis. The two most frequent phenotypes are childhood cerebral adrenoleukodystrophy (CCALD) and adrenomyeloneuropathy (AMN). Some affected males demonstrate no clinical signs (asymptomatic ALD), whereas female carriers can also be affected. Patients with X-ALD have been treated with Lorenzo's oil, a 4:1 combination of oleic acid and erucic acid, with thrombocytopenia as the main side effect and sometimes leading to a hemorrhagic diathesis. We studied platelet count, size and membrane surface exposure of platelet activation antigens in 17 adult X-ALD patients. Eight patients used the prescribed amount of erucic acid (as glyceroltrierucate) or more (very compliant), five used less(compliant), and four did not use the diet. All eight very compliant patients had highly enlarged platelets and seven manifested thrombocytopenia. An enhanced in vivo platelet activation status was established by increased platelet surface expression of P-selectin (CD62P, PADGEM, GMP-140) in five of the seven thrombocytopenic patients, and of increased fibrinogen receptor exposure (measured with the antibody PAC-1) in three of these five patients. The other nine compliant or untreated patients had normal platelet counts and, generally, normal P-selection and fibrinogen receptor expression. A diet-induced 7- to 27-fold enrichment of erucic acid was observed in the platelets of the four patients studied. We conclude that the thrombocytopenia in AMN patients using Lorenzo'soil is associated with circulating platelets that have an increased erucic acid content, size and activation status. We hypothesize that the erucic acid in some way induces the increased size and thus, directly or indirectly, increased platelet activation or instability in vivo. This then causes the thrombocytopenia

  8. 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

  9. 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

    2015-01-01

    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.

  10. Erythorbyl laurate as a potential food additive with multi-functionalities: Interfacial characteristics and antioxidant activity.

    PubMed

    Park, Kyung-Min; Lee, Min Joo; Jo, Su-Kyung; Choi, Seung Jun; Lee, JaeHwan; Chang, Pahn-Shick

    2017-01-15

    The interfacial characteristics and antioxidant activities of erythorbyl laurate were investigated to provide information on practical applications as a multi-functional food additive. The critical micelle concentration (CMC) of erythorbyl laurate was 0.101mM and its foam stability was three times (half-life 24.33±0.94h) higher than that of Tween 20 (8.00±1.63h). In free radical scavenging assay, the negligible decrease in EC50 of erythorbyl laurate compared to erythorbic acid manifested that C-5 selective esterification of erythorbic acid with an acyl group (lauric acid) did not reduce the inherent antioxidant activity of the donor (erythorbic acid). Erythorbyl laurate formed lipid peroxides slower (i.e. retarded oxidation) in an emulsion system than did erythorbic acid. The localization of erythorbyl laurate as an emulsifier allowed the antioxidant molecules to be concentrated at the oil-water interface where oxidation is prevalent, which led to more effective retardation of lipid oxidation. PMID:27542455

  11. Switch of SpnR function from activating to inhibiting quorum sensing by its exogenous addition.

    PubMed

    Takayama, Yuriko; Kato, Norihiro

    2016-09-01

    The opportunistic human pathogen Serratia marcescens AS-1 produces the N-hexanoylhomoserine lactone (C6HSL) receptor SpnR, a homologue of LuxR from Vibrio fischeri, which activates pig clusters to produce the antibacterial prodigiosin. In this study, we attempted to artificially regulate quorum sensing (QS) by changing the role of SpnR in N-acylhomoserine lactone (AHL)-mediated QS. SpnR was obtained as a fusion protein tagged with maltose-binding protein (MBP) from overexpression in Escherichia coli, and its specific affinity to C6HSL was demonstrated by quartz crystal microbalance analysis and AHL-bioassay with Chromobacterium violaceum CV026. Prodigiosin production was effectively inhibited by externally added MBP-SpnR in both wild-type AS-1 and the AHL synthase-defective mutant AS-1(ΔspnI). For the mutant, the induced amount of prodigiosin was drastically reduced to approximately 4% with the addition of 18 μM MBP-SpnR to the liquid medium, indicating 81% trapping of C6HSL. A system for inhibiting QS can be constructed by adding exogenous AHL receptor to the culture broth to keep the concentration of free AHL low, whereas intracellular SpnR naturally functions as the activator in response to QS. PMID:27387237

  12. Switch of SpnR function from activating to inhibiting quorum sensing by its exogenous addition.

    PubMed

    Takayama, Yuriko; Kato, Norihiro

    2016-09-01

    The opportunistic human pathogen Serratia marcescens AS-1 produces the N-hexanoylhomoserine lactone (C6HSL) receptor SpnR, a homologue of LuxR from Vibrio fischeri, which activates pig clusters to produce the antibacterial prodigiosin. In this study, we attempted to artificially regulate quorum sensing (QS) by changing the role of SpnR in N-acylhomoserine lactone (AHL)-mediated QS. SpnR was obtained as a fusion protein tagged with maltose-binding protein (MBP) from overexpression in Escherichia coli, and its specific affinity to C6HSL was demonstrated by quartz crystal microbalance analysis and AHL-bioassay with Chromobacterium violaceum CV026. Prodigiosin production was effectively inhibited by externally added MBP-SpnR in both wild-type AS-1 and the AHL synthase-defective mutant AS-1(ΔspnI). For the mutant, the induced amount of prodigiosin was drastically reduced to approximately 4% with the addition of 18 μM MBP-SpnR to the liquid medium, indicating 81% trapping of C6HSL. A system for inhibiting QS can be constructed by adding exogenous AHL receptor to the culture broth to keep the concentration of free AHL low, whereas intracellular SpnR naturally functions as the activator in response to QS.

  13. Erythorbyl laurate as a potential food additive with multi-functionalities: Interfacial characteristics and antioxidant activity.

    PubMed

    Park, Kyung-Min; Lee, Min Joo; Jo, Su-Kyung; Choi, Seung Jun; Lee, JaeHwan; Chang, Pahn-Shick

    2017-01-15

    The interfacial characteristics and antioxidant activities of erythorbyl laurate were investigated to provide information on practical applications as a multi-functional food additive. The critical micelle concentration (CMC) of erythorbyl laurate was 0.101mM and its foam stability was three times (half-life 24.33±0.94h) higher than that of Tween 20 (8.00±1.63h). In free radical scavenging assay, the negligible decrease in EC50 of erythorbyl laurate compared to erythorbic acid manifested that C-5 selective esterification of erythorbic acid with an acyl group (lauric acid) did not reduce the inherent antioxidant activity of the donor (erythorbic acid). Erythorbyl laurate formed lipid peroxides slower (i.e. retarded oxidation) in an emulsion system than did erythorbic acid. The localization of erythorbyl laurate as an emulsifier allowed the antioxidant molecules to be concentrated at the oil-water interface where oxidation is prevalent, which led to more effective retardation of lipid oxidation.

  14. Cell-free synthesis of enzymically active tissue-type plasminogen activator. Protein folding determines the extent of N-linked glycosylation.

    PubMed Central

    Bulleid, N J; Bassel-Duby, R S; Freedman, R B; Sambrook, J F; Gething, M J

    1992-01-01

    Tissue-type plasminogen activator (t-PA) is synthesized in mammalian cells as a mixture of two forms that differ in their extent of N-linked glycosylation. We have investigated the mechanism underlying this variation in glycosylation, using a cell-free system that consists of a rabbit reticulocyte lysate optimized for the formation of disulphide bonds and supplemented with dog pancreas microsomal membranes. Molecules of human t-PA synthesized in vitro are enzymically active and responsive to natural activators and inhibitors, and are glycosylated in a pattern identical with that of the protein produced in vivo. This demonstrates that t-PA synthesized in vitro folds into the same conformation as the protein synthesized in vivo. We show that the extent of glycosylation of individual t-PA molecules is dependent on the state of folding of the polypeptide chain, since the probability of addition of an oligosaccharide side chain at Asn-184 is decreased under conditions that promote the formation of enzymically active molecules. This variation in glycosylation is independent of the rate of protein synthesis. Images Fig. 3. Fig. 4. Fig. 5. Fig. 6. PMID:1520279

  15. Screening of Dengue Virus Antiviral Activity of Marine Seaweeds by an In Situ Enzyme-Linked Immunosorbent Assay

    PubMed Central

    Koishi, Andrea Cristine; Zanello, Paula Rodrigues; Bianco, Éverson Miguel; Bordignon, Juliano; Nunes Duarte dos Santos, Claudia

    2012-01-01

    Dengue is a significant public health problem worldwide. Despite the important social and clinical impact, there is no vaccine or specific antiviral therapy for prevention and treatment of dengue virus (DENV) infection. Considering the above, drug discovery research for dengue is of utmost importance; in addition natural marine products provide diverse and novel chemical structures with potent biological activities that must be evaluated. In this study we propose a target-free approach for dengue drug discovery based on a novel, rapid, and economic in situ enzyme-linked immunosorbent assay and the screening of a panel of marine seaweed extracts. The in situ ELISA was standardized and validated for Huh7.5 cell line infected with all four serotypes of DENV, among them clinical isolates and a laboratory strain. Statistical analysis showed an average S/B of 7.2 and Z-factor of 0.62, demonstrating assay consistency and reliability. A panel of fifteen seaweed extracts was then screened at the maximum non-toxic dose previously determined by the MTT and Neutral Red cytotoxic assays. Eight seaweed extracts were able to reduce DENV infection of at least one serotype tested. Four extracts (Phaeophyta: Canistrocarpus cervicornis, Padina gymnospora; Rhodophyta: Palisada perforate; Chlorophyta: Caulerpa racemosa) were chosen for further evaluation, and time of addition studies point that they might act at an early stage of the viral infection cycle, such as binding or internalization. PMID:23227238

  16. 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.

  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. 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…

  19. 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...

  20. Evidence for a link between global lightning activity and upper tropospheric water vapour

    PubMed

    Price

    2000-07-20

    Tropospheric water vapour is a key element of the Earth's climate, which has direct effects as a greenhouse gas, as well as indirect effects through interaction with clouds, aerosols and tropospheric chemistry. Small changes in upper-tropospheric water vapour have a much larger impact on the greenhouse effect than small changes in water vapour in the lower atmosphere, but whether this impact is a positive or negative feedback remains uncertain. The main challenge in addressing this question is the difficulty in monitoring upper-tropospheric water vapour globally over long timescales. Here I show that upper-tropospheric water-vapour variability and global lightning activity are closely linked, suggesting that upper-tropospheric water-vapour changes can be inferred from records of global lightning activity, readily obtained from observations at a single location on the Earth's surface. This correlation reflects the fact that continental deep-convective thunderstorms transport large amounts of water vapour into the upper troposphere and thereby dominate the variations of global upper-tropospheric water vapour while producing most of the lightning on Earth. As global lightning induces Schumann resonances, an electromagnetic phenomenon in the atmosphere that can be observed easily at low cost, monitoring of these resonances might provide a convenient method for tracking upper-tropospheric water-vapour variability and hence contribute to a better understanding of the processes affecting climate change.

  1. 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

  2. Catalytic activity of non-cross-linked microcrystals of aspartate aminotransferase in poly(ethylene glycol).

    PubMed Central

    Kirsten, H; Christen, P

    1983-01-01

    The molar activity of crystalline mitochondrial aspartate aminotransferase is decreased to 10% of that of the enzyme in solution. The activity was measured in suspensions of non-cross-linked microcrystals (average dimensions 22 microns X 5 microns X 0.8 microns) in 30% (w/v) poly(ethylene glycol). Kinetic tests ruled out the possibility that diffusion of the substrate in the crystals is rate-limiting. The observed decrease in catalytic efficiency can be attributed exclusively to crystal-packing effects. A direct inhibition by poly(ethylene glycol) is excluded because poly(ethylene glycol), with average Mr 6000, cannot penetrate the liquid channels of the crystals, owing to its large Stokes radius. The crystals examined were triclinic and of the same habit as those used for high-resolution X-ray-crystallographic analysis [Ford, Eichele & Jansonius (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 2559-2563]. The catalytic competence of crystalline aspartate aminotransferase confirms the relevance of the spatial model of this protein for the elucidation of its mechanism of action. Images Fig. 1. PMID:6870840

  3. Bilirubin, platelet activation and heart disease: a missing link to cardiovascular protection in Gilbert's syndrome?

    PubMed

    Kundur, Avinash R; Singh, Indu; Bulmer, Andrew C

    2015-03-01

    Gilbert's syndrome (GS) is a relatively common condition, inducing a benign, non-hemolytic, unconjugated hyperbilirubinemia. Gilbert's Syndrome is associated with mutation in the Uridine Glucuronosyl Transferase 1A1 (UGT1A1) gene promoter, reducing UGT1A1 activity, which normally conjugates bilirubin allowing its elimination from the blood. Individuals with GS demonstrate mildly elevated plasma antioxidant capacity caused by elevated levels of unconjugated bilirubin (UCB), reduced thiols and glutathione. Interestingly, the development of, and risk of mortality from, cardiovascular disease is remarkably reduced in GS individuals. An explanation for this protection may be explained by bilirubin's ability to inhibit multiple processes that induce platelet hyper-reactivity and thrombosis, thus far under-appreciated in the literature. Reactive oxygen species are produced continuously via metabolic processes and have the potential to oxidatively modify proteins and lipids within cell membranes, which may encourage the development of thrombosis and CVDs. Oxidative stress induced platelet hyper-reactivity significantly increases the risk of thrombosis, which can potentially lead to tissue infarction. Here, we discuss the possible mechanisms by which increased antioxidant status might influence platelet function and link this to cardiovascular protection in GS. In summary, this is the first article to discuss the possible role of bilirubin as an anti-thrombotic agent, which inhibits platelet activation and potentially, organ infarction, which could contribute to the reduced mortality rate in mildly hyperbilirbinemic individuals. PMID:25576848

  4. Bifunctional reactivity of amidoximes observed upon nucleophilic addition to metal-activated nitriles.

    PubMed

    Bolotin, Dmitrii S; Demakova, Marina Ya; Novikov, Alexander S; Avdontceva, Margarita S; Kuznetsov, Maxim L; Bokach, Nadezhda A; Kukushkin, Vadim Yu

    2015-04-20

    Treatment of the aromatic nitrile complexes trans-[PtCl2(RC6H4CN)2] (R = p-CF3 NC1, H NC2, o-Cl NC3) with the aryl amidoximes p-R'C6H4C(NH2)=NOH (R' = Me AO1, H AO2, Br AO3, CF3 AO4, NO2 AO5) in all combinations, followed by addition of 1 equiv of AgOTf and then 5 equiv of Et3N, leads to the chelates [PtCl{HN=C(RC6H4)ON=C(C6H4R'-p)NC(RC6H4)═NH}] (1-15; 15 examples; yields 71-88% after column chromatography) derived from the platinum(II)-mediated coupling between metal-activated nitriles and amidoximes. The mechanism of this reaction was studied experimentally by trapping and identification of the reaction intermediates, and it was also investigated theoretically at the DFT level of theory. The combined experimental and theoretical results indicate that the coupling with the nitrile ligands involves both the HON and monodeprotonated NH2 groups of the amidoximes, whereas in the absence of the base, the NH2 functionality is inactive toward the coupling. The observed reaction represents the first example of bifunctional nucleophilic behavior of amidoximes. The complexes 1-16 were characterized by elemental analyses (C, H, N), high-resolution ESI(+)-MS, FTIR, and (1)H NMR techniques, whereas unstable 17 was characterized by HRESI(+)-MS and FTIR. In addition, 8·C4H8O2, 12, and 16·CHCl3 were studied by single-crystal X-ray diffraction. PMID:25822628

  5. Interplay of solvent additive concentration and active layer thickness on the performance of small molecule solar cells.

    PubMed

    Love, John A; Collins, Samuel D; Nagao, Ikuhiro; Mukherjee, Subhrangsu; Ade, Harald; Bazan, Guillermo C; Nguyen, Thuc-Quyen

    2014-11-19

    A relationship between solvent additive concentration and active layer thickness in small-molecule solar cells is investigated. Specifically, the additive concentration must scale with the amount of semiconductor material and not as absolute concentration in solution. Devices with a wide range of active layers with thickness up to 200 nm can readily achieve efficiencies close to 6% when the right concentration of additive is used.

  6. 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

  7. 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

  8. 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)

  9. Biochemical analyses of the antioxidative activity and chemical ingredients in eight different Allium alien monosomic addition lines.

    PubMed

    Yaguchi, Shigenori; Matsumoto, Misato; Date, Rie; Harada, Kazuki; Maeda, Toshimichi; Yamauchi, Naoki; Shigyo, Masayoshi

    2013-01-01

    We measured the antioxidant contents and antioxidative activities in eight Allium fistulosum-shallot monosomic addition lines (MAL; FF+1A-FF+8A). The high antioxidative activity lines (FF+2A and FF+6A) showed high polyphenol accumulation. These additional chromosomes (2A and 6A) would therefore have anonymous genes related to the upregulation of polyphenol production, the antioxidative activities consequently being increased in these MALs. PMID:24317054

  10. 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

  11. Para-aminobenzamidine linked regenerated cellulose membranes for plasminogen activator purification: Effect of spacer arm length and ligand density

    PubMed Central

    Fasoli, Ezio; Reyes, Yiaslin Ruiz; Guzman, Osiris Martinez; Rosado, Alexandra; Cruz, Vivian Rodriguez; Borges, Amaris; Martinez, Edmarie; Bansal, Vibha

    2013-01-01

    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 (5–25 nmoles per cm2). 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 nmole 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 monocomponent 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±1.0 nmoles per cm2) 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. PMID:23703544

  12. 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.

  13. 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...

  14. Cross-linked enzyme aggregates (CLEAs) of Pencilluim notatum lipase enzyme with improved activity, stability and reusability characteristics.

    PubMed

    Rehman, Saima; Bhatti, Haq Nawaz; Bilal, Muhammad; Asgher, Muhammad

    2016-10-01

    Cross-linked enzyme aggregates (CLEAs) are considered as an effective tool for the immobilization of enzyme. In this study, Pencillium notatum lipase (PNL) was immobilized as carrier free cross-linked enzyme aggregates using glutaraldehyde (GLA) and Ethylene glycol-bis [succinic acid N-hydroxysuccinimide] (EG-NHS) as cross-linking agents. The optimal conditions for the synthesis of an efficient lipase CLEAs such as precipitant type, the nature and amount of cross-linking reagent, and cross-linking time were optimized. The recovered activities of CLEAs were considerably dependent on the concentration of GLA; however, the activity recovery was not severely affected by EG-NHS as a mild cross-linker. The EG-NHS aggregates displayed superior hydrolytic (52.08±2.52%) and esterification (64.42%) activities as compared to GLA aggregates which showed 23.8±1.86 and 34.54% of hydrolytic and esterification activity, respectively. Morphological analysis by fluorescence and scanning electron microscope revealed that EG-NHS aggregates were smaller in size with larger surface area compared to GLA aggregates. The pH optima of both types of CLEAs were displaced to slightly alkaline region and higher temperature as compared to native enzyme. Highest enzyme activity of CLEAs was achieved at the pH of 9.0 and 42°C temperature. Moreover, a significant improvement in the thermal resistance was also recorded after immobilization. After ten reusability cycles in aqueous medium, GLA and EG-NHS cross-linked lipase CLEAs preserved 63.62% and 70.9% of their original activities, respectively. The results suggest that this novel CLEA-lipase is potentially usable in many industrial applications.

  15. Cross-linked enzyme aggregates (CLEAs) of Pencilluim notatum lipase enzyme with improved activity, stability and reusability characteristics.

    PubMed

    Rehman, Saima; Bhatti, Haq Nawaz; Bilal, Muhammad; Asgher, Muhammad

    2016-10-01

    Cross-linked enzyme aggregates (CLEAs) are considered as an effective tool for the immobilization of enzyme. In this study, Pencillium notatum lipase (PNL) was immobilized as carrier free cross-linked enzyme aggregates using glutaraldehyde (GLA) and Ethylene glycol-bis [succinic acid N-hydroxysuccinimide] (EG-NHS) as cross-linking agents. The optimal conditions for the synthesis of an efficient lipase CLEAs such as precipitant type, the nature and amount of cross-linking reagent, and cross-linking time were optimized. The recovered activities of CLEAs were considerably dependent on the concentration of GLA; however, the activity recovery was not severely affected by EG-NHS as a mild cross-linker. The EG-NHS aggregates displayed superior hydrolytic (52.08±2.52%) and esterification (64.42%) activities as compared to GLA aggregates which showed 23.8±1.86 and 34.54% of hydrolytic and esterification activity, respectively. Morphological analysis by fluorescence and scanning electron microscope revealed that EG-NHS aggregates were smaller in size with larger surface area compared to GLA aggregates. The pH optima of both types of CLEAs were displaced to slightly alkaline region and higher temperature as compared to native enzyme. Highest enzyme activity of CLEAs was achieved at the pH of 9.0 and 42°C temperature. Moreover, a significant improvement in the thermal resistance was also recorded after immobilization. After ten reusability cycles in aqueous medium, GLA and EG-NHS cross-linked lipase CLEAs preserved 63.62% and 70.9% of their original activities, respectively. The results suggest that this novel CLEA-lipase is potentially usable in many industrial applications. PMID:27365121

  16. Cyclotide Structure–Activity Relationships: Qualitative and Quantitative Approaches Linking Cytotoxic and Anthelmintic Activity to the Clustering of Physicochemical Forces

    PubMed Central

    Park, Sungkyu; Strömstedt, Adam A.; Göransson, Ulf

    2014-01-01

    Cyclotides are a family of plant-derived proteins that are characterized by a cyclic backbone and a knotted disulfide topology. Their cyclic cystine knot (CCK) motif makes them exceptionally resistant to thermal, chemical, and enzymatic degradation. Cyclotides exert much of their biological activity via interactions with cell membranes. In this work, we qualitatively and quantitatively analyze the cytotoxic and anthelmintic membrane activities of cyclotides. The qualitative and quantitative models describe the potency of cyclotides using four simple physicochemical terms relevant to membrane contact. Specifically, surface areas of the cyclotides representing lipophilic and hydrogen bond donating properties were quantified and their distribution across the molecular surface was determined. The resulting quantitative structure-activity relation (QSAR) models suggest that the activity of the cyclotides is proportional to their lipophilic and positively charged surface areas, provided that the distribution of these surfaces is asymmetric. In addition, we qualitatively analyzed the physicochemical differences between the various cyclotide subfamilies and their effects on the cyclotides' orientation on the membrane and membrane activity. PMID:24682019

  17. Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome.

    PubMed

    White, Andrea T; Light, Alan R; Hughen, Ronald W; Bateman, Lucinda; Martins, Thomas B; Hill, Harry R; Light, Kathleen C

    2010-07-01

    Chronic fatigue syndrome (CFS) patients often report symptom flare (SF) for >24 h after moderate exercise (post-ex). We hypothesized that SF is linked to increases in circulating cytokines and CD40 Ligand (CD40L). In 19 CFS patients and 17 controls, mental and physical fatigue and pain symptom ratings were obtained together with serum for 11 cytokines and CD40L before and at 0.5, 8, 24, and 48 h post-ex. Before exercise, CFS had lower CD40L (p<.05) but similar cytokines versus controls. In subgroups based on SF at 48 h, high SF patients (n=11) increased in IL-1beta, IL-12, IL-6, IL-8, IL-10, and IL-13 (p<.05) 8 h post-ex. Low SF patients (n=8) showed post-ex decreases in IL-10, IL-13, and CD40L, and controls decreased in IL-10, CD40L, and TNFalpha (p<.05). Thus, in CFS, cytokine activity may vary directly with SF, which may explain prior inconsistent findings.

  18. 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.

  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. Enhancement of mechanical properties, microstructure, and antimicrobial activities of zein films cross-linked using succinic anhydride, eugenol, and citric Acid.

    PubMed

    Khalil, Ashraf A; Deraz, Sahar F; Elrahman, Somia Abd; El-Fawal, Gomaa

    2015-08-18

    Zein constitutes about half of the endosperm proteins in corn. Recently, attempts have been made to utilize zein for food coatings and biodegradable materials, which require better physical properties, using chemical modification of zein. In this study, zein proteins were modified using citric acid, succinic anhydride, and eugenol as natural cross-linking agents in the wet state. The cross-linkers were added either separately or combined in increment concentrations (0.1, 0.2, 0.3, and 0.4%). The effects of those agents on the mechanical properties, microstructure, optical properties, infrared (IR) spectroscopy, and antibacterial activities of zein were investigated. The addition of cross-linking agents promoted changes in the arrangement of groups in zein film-forming particles. Regarding the film properties, incorporation of cross-linking agents into zein films prepared in ethanol resulted in two- to three-fold increases in tensile strength (TS) values. According to the Fourier-transform infrared (FTIR) spectra and Hunter parameters there were no remarkable changes in the structure and color of zein films. Transparency of zein films was decreased differentially according to the type and cross-linker concentration. The mechanical and optical properties of zein films were closely related to their microstructure. All cross-linked films showed remarkable antibacterial activities against Bacillus cereus ATCC 49064 and Salmonella enterica ATCC 25566. Food spoilage and pathogenic bacteria were affected in a film-dependent manner. Our experimental results show that even with partial cross-linking the mechanical properties and antipathogen activities of zein films were significantly improved, which would be useful for various industrial applications.

  1. Assessing activity limitations in patients with neuromuscular diseases: is the ACTIVLIM questionnaire linked to ICF and ICF-CY?

    PubMed

    Raggi, Alberto; Leonardi, Matilde

    2009-06-01

    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 Health (ICF), and to its Children and Youth version (ICF-CY). Standardized ICF linking rules were applied. Items were linked to the most specific ICF-CY codes (e.g. d4501 - Walking long distances), and rolling-up procedures were applied to report information to more generic and informative upper-level codes (e.g. d450 - Walking). ACTIVLIM items were linked to 13 second-level ICF codes of Mobility, Self-care, and Domestic life chapters. The majority of ACTIVLIM items are liked to d510 - Washing oneself, d445 - Hand and arm use, and d410 - Changing basic body position. None of the ACTIVLIM items links to the codes added by the new ICF-CY classification. Disability is a multidimensional phenomenon, and measurements of disability should reflect this multidimensionality. The good psychometric properties of ACTIVLIM are demonstrated, and the aim of this mapping exercise is to provide information on its content. A relevant part of ACTIVLIM items is linked to a few ICF codes, referred to as basic body movements and washing, and other activities are less represented. We think that the ACTIVLIM covers a circumscribed set of activities and, therefore, we suggest using it together with other functional evaluation tools, to complement the range of information on activity limitations that are not covered by its items.

  2. 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.

  3. 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.

  4. Metabolic Features of Protochlamydia amoebophila Elementary Bodies – A Link between Activity and Infectivity in Chlamydiae

    PubMed Central

    Watzka, Margarete; Wultsch, Anna; Tziotis, Dimitrios; Montanaro, Jacqueline; Richter, Andreas; Schmitt-Kopplin, Philippe; Horn, Matthias

    2013-01-01

    The Chlamydiae are a highly successful group of obligate intracellular bacteria, whose members are remarkably diverse, ranging from major pathogens of humans and animals to symbionts of ubiquitous protozoa. While their infective developmental stage, the elementary body (EB), has long been accepted to be completely metabolically inert, it has recently been shown to sustain some activities, including uptake of amino acids and protein biosynthesis. In the current study, we performed an in-depth characterization of the metabolic capabilities of EBs of the amoeba symbiont Protochlamydia amoebophila. A combined metabolomics approach, including fluorescence microscopy-based assays, isotope-ratio mass spectrometry (IRMS), ion cyclotron resonance Fourier transform mass spectrometry (ICR/FT-MS), and ultra-performance liquid chromatography mass spectrometry (UPLC-MS) was conducted, with a particular focus on the central carbon metabolism. In addition, the effect of nutrient deprivation on chlamydial infectivity was analyzed. Our investigations revealed that host-free P. amoebophila EBs maintain respiratory activity and metabolize D-glucose, including substrate uptake as well as host-free synthesis of labeled metabolites and release of labeled CO2 from 13C-labeled D-glucose. The pentose phosphate pathway was identified as major route of D-glucose catabolism and host-independent activity of the tricarboxylic acid (TCA) cycle was observed. Our data strongly suggest anabolic reactions in P. amoebophila EBs and demonstrate that under the applied conditions D-glucose availability is essential to sustain metabolic activity. Replacement of this substrate by L-glucose, a non-metabolizable sugar, led to a rapid decline in the number of infectious particles. Likewise, infectivity of Chlamydia trachomatis, a major human pathogen, also declined more rapidly in the absence of nutrients. Collectively, these findings demonstrate that D-glucose is utilized by P. amoebophila EBs and provide

  5. Metabolic features of Protochlamydia amoebophila elementary bodies--a link between activity and infectivity in Chlamydiae.

    PubMed

    Sixt, Barbara S; Siegl, Alexander; Müller, Constanze; Watzka, Margarete; Wultsch, Anna; Tziotis, Dimitrios; Montanaro, Jacqueline; Richter, Andreas; Schmitt-Kopplin, Philippe; Horn, Matthias

    2013-01-01

    The Chlamydiae are a highly successful group of obligate intracellular bacteria, whose members are remarkably diverse, ranging from major pathogens of humans and animals to symbionts of ubiquitous protozoa. While their infective developmental stage, the elementary body (EB), has long been accepted to be completely metabolically inert, it has recently been shown to sustain some activities, including uptake of amino acids and protein biosynthesis. In the current study, we performed an in-depth characterization of the metabolic capabilities of EBs of the amoeba symbiont Protochlamydia amoebophila. A combined metabolomics approach, including fluorescence microscopy-based assays, isotope-ratio mass spectrometry (IRMS), ion cyclotron resonance Fourier transform mass spectrometry (ICR/FT-MS), and ultra-performance liquid chromatography mass spectrometry (UPLC-MS) was conducted, with a particular focus on the central carbon metabolism. In addition, the effect of nutrient deprivation on chlamydial infectivity was analyzed. Our investigations revealed that host-free P. amoebophila EBs maintain respiratory activity and metabolize D-glucose, including substrate uptake as well as host-free synthesis of labeled metabolites and release of labeled CO2 from (13)C-labeled D-glucose. The pentose phosphate pathway was identified as major route of D-glucose catabolism and host-independent activity of the tricarboxylic acid (TCA) cycle was observed. Our data strongly suggest anabolic reactions in P. amoebophila EBs and demonstrate that under the applied conditions D-glucose availability is essential to sustain metabolic activity. Replacement of this substrate by L-glucose, a non-metabolizable sugar, led to a rapid decline in the number of infectious particles. Likewise, infectivity of Chlamydia trachomatis, a major human pathogen, also declined more rapidly in the absence of nutrients. Collectively, these findings demonstrate that D-glucose is utilized by P. amoebophila EBs and provide

  6. F{sub o}F{sub 1}-ATPase activity regulated by external links on {beta} subunits

    SciTech Connect

    Cheng, Jie; Zhang, Xiao-ai; Shu, Yao-Gen; Yue, Jia-Chang

    2010-01-01

    F{sub o}F{sub 1}-ATPase activity is regulated by external links on {beta} subunits with different molecular weight. It is inhibited when anti-{beta} subunit antibody, streptavidin and H9 antibody link on the {beta} subunits successively, but is activated when virus was binded. Western blotting indicated that the employed anti-{beta} antibody target was on the non-catalytic site of the {beta} subunit. Furthermore, an ESR study of spin-labeled ATP (SL-ATP) showed that the affinity of ATP to the holoenzyme increases with increasing external links on the {beta} subunits. This simple regulation method may have great potential in the design of rapid, free labeled, sensitive and selective biosensors.

  7. 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...

  8. 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...

  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, 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...

  11. 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...

  12. Linking inter-individual differences in the conflict adaptation effect to spontaneous brain activity.

    PubMed

    Wang, Ting; Chen, Zhencai; Zhao, Guang; Hitchman, Glenn; Liu, Congcong; Zhao, Xiaoyue; Liu, Yijun; Chen, Antao

    2014-04-15

    Conflict adaptation has been widely researched in normal and clinical populations. There are large individual differences in conflict adaptation, and it has been linked to the schizotypal trait. However, no study to date has examined how individual differences in spontaneous brain activity are related to behavioral conflict adaptation (performance). Resting-state functional magnetic resonance imaging (RS-fMRI) is a promising tool to investigate this issue. The present study evaluated the regional homogeneity (ReHo) of RS-fMRI signals in order to explore the neural basis of individual differences in conflict adaptation across two independent samples comprising a total of 67 normal subjects. A partial correlation analysis was carried out to examine the relationship between ReHo and behavioral conflict adaptation, while controlling for reaction time, standard deviation and flanker interference effects. This analysis was conducted on 39 subjects' data (sample 1); the results showed significant positive correlations in the left dorsolateral prefrontal cortex (DLPFC) and left ventrolateral prefrontal cortex. We then conducted a test-validation procedure on the remaining 28 subjects' data (sample 2) to examine the reliability of the results. Regions of interest were defined based on the correlation results. Regression analysis showed that variability in ReHo values in the DLPFC accounted for 48% of the individual differences in the conflict adaptation effect in sample 2. The present findings provide further support for the importance of the DLPFC in the conflict adaptation process. More importantly, we demonstrated that ReHo of RS-fMRI signals in the DLPFC can predict behavioral performance in conflict adaptation, which provides potential biomarkers for the early detection of cognitive control deterioration.

  13. 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

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

    PubMed Central

    Heck, A.; Fastenrath, M.; Ackermann, S.; Auschra, B.; Bickel, H.; Coynel, D.; Gschwind, L.; Jessen, F.; Kaduszkiewicz, H.; Maier, W.; Milnik, A.; Pentzek, M.; Riedel-Heller, S.G.; Ripke, S.; Spalek, K.; Sullivan, P.; Vogler, C.; Wagner, M.; Weyerer, S.; Wolfsgruber, S.; de Quervain, D.; Papassotiropoulos, A.

    2014-01-01

    Summary 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. PMID:24529980

  15. Activation energies control the macroscopic properties of physically cross-linked materials.

    PubMed

    Appel, Eric A; Forster, Rebecca A; Koutsioubas, Alexandros; Toprakcioglu, Chris; Scherman, Oren A

    2014-09-15

    Here we show the preparation of a series of water-based physically cross-linked polymeric materials utilizing cucurbit[8]uril (CB[8]) ternary complexes displaying a range of binding, and therefore cross-linking, dynamics. We determined that the mechanical strength of these materials is correlated directly with a high energetic barrier for the dissociation of the CB[8] ternary complex cross-links, whereas facile and rapid self-healing requires a low energetic barrier to ternary complex association. The versatile CB[8] ternary complex has, therefore, proven to be a powerful asset for improving our understanding of challenging property-structure relationships in supramolecular systems and their associated influence on the bulk behavior of dynamically cross-linked materials.

  16. 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...

  17. 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...

  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, 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...

  20. 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...

  1. 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. PMID:26940967

  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. 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. PMID:26901714

  4. 42 CFR 424.516 - Additional provider and supplier requirements for enrolling and maintaining active enrollment...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... the HHS Common Rule at 45 CFR part 76. (b) Reporting requirements Independent Diagnostic Testing... enrolling and maintaining active enrollment status in the Medicare program. 424.516 Section 424.516 Public... active enrollment status in the Medicare program. (a) Certifying compliance. CMS enrolls and maintains...

  5. 42 CFR 424.516 - Additional provider and supplier requirements for enrolling and maintaining active enrollment...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... the HHS Common Rule at 45 CFR part 76. (b) Reporting requirements Independent Diagnostic Testing... enrolling and maintaining active enrollment status in the Medicare program. 424.516 Section 424.516 Public... active enrollment status in the Medicare program. (a) Certifying compliance. CMS enrolls and maintains...

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

    PubMed

    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.

  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. 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.

  9. Unconventional Bifunctional Lewis-Brønsted Acid Activation Mode in Bicyclic Guanidine-Catalyzed Conjugate Addition Reactions.

    PubMed

    Cho, Bokun; Wong, Ming Wah

    2015-08-18

    DFT calculations have demonstrated that the unconventional bifunctional Brønsted-Lewis acid activation mode is generally applicable to a range of nucleophilic conjugate additions catalyzed by bicyclic guanidine catalysts. It competes readily with the conventional bifunctional Brønsted acid mode of activation. The optimal pro-nucleophiles for this unconventional bifunctional activation are acidic substrates with low pKa, while the best electrophiles are flexible 1,4-diamide and 1,4-diester conjugated systems.

  10. 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

  11. 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.

  12. 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

  13. The effects of addition of mononucleotides on Sma nuc endonuclease activity.

    PubMed

    Romanova, Julia; Filimonova, Maria

    2012-01-01

    Examination of the effects of mononucleotides on Sma nuc endonuclease originated from Gram negative bacterium Serratia marcescens displayed that any mononucleotide produced by Sma nuc during hydrolysis of DNA or RNA may regulate the enzyme activity affecting the RNase activity without pronounced influence on the activity towards DNA. The type of carbohydrate residue in mononucleotides does not affect the regulation. In contrast, the effects depend on the type of bases in nucleotides. AMP or dAMP was classified as a competitive inhibitor of partial type. GMP, UMP, and CMP were found to be uncompetitive inhibitors that suggest a specific site(s) for the nucleotide(s) binding in Sma nuc endonuclease.

  14. Actively-targeted polyion complex micelles stabilized by cholesterol and disulfide cross-linking for systemic delivery of siRNA to solid tumors.

    PubMed

    Oe, Yusuke; Christie, R James; Naito, Mitsuru; Low, Stewart A; Fukushima, Shigeto; Toh, Kazuko; Miura, Yutaka; Matsumoto, Yu; Nishiyama, Nobuhiro; Miyata, Kanjiro; Kataoka, Kazunori

    2014-09-01

    For small interfering RNA (siRNA)-based cancer therapies, we report an actively-targeted and stabilized polyion complex micelle designed to improve tumor accumulation and cancer cell uptake of siRNA following systemic administration. Improvement in micelle stability was achieved using two stabilization mechanisms; covalent disulfide cross-linking and non-covalent hydrophobic interactions. The polymer component was designed to provide disulfide cross-linking and cancer cell-targeting cyclic RGD peptide ligands, while cholesterol-modified siRNA (Chol-siRNA) provided additional hydrophobic stabilization to the micelle structure. Dynamic light scattering confirmed formation of nano-sized disulfide cross-linked micelles (<50 nm in diameter) with a narrow size distribution. Improved stability of Chol-siRNA-loaded micelles (Chol-siRNA micelles) was demonstrated by resistance to both the dilution in serum-containing medium and counter polyion exchange with dextran sulfate, compared to control micelles prepared with Chol-free siRNA (Chol-free micelles). Improved stability resulted in prolonged blood circulation time of Chol-siRNA micelles compared to Chol-free micelles. Furthermore, introduction of cRGD ligands onto Chol-siRNA micelles significantly facilitated accumulation of siRNA in a subcutaneous cervical cancer model following systemic administration. Ultimately, systemically administered cRGD/Chol-siRNA micelles exhibited significant gene silencing activity in the tumor, presumably due to their active targeting ability combined with the enhanced stability through both hydrophobic interactions of cholesterol and disulfide cross-linking. PMID:24930854

  15. DNA markers closely linked to nematode resistance genes in sugar beet (Beta vulgaris L.) mapped using chromosome additions and translocations originating from wild beets of the Procumbentes section.

    PubMed

    Jung, C; Koch, R; Fischer, F; Brandes, A; Wricke, G; Herrmann, R G

    1992-03-01

    Genes conferring resistance to the beet cyst nematode (Heterodera schachtii Schm.) have been transferred to sugar beet (Beta vulgaris L.) from three wild species of the Procumbentes section using monosomic addition and translocation lines, because no meiotic recombination occurs between chromosomes of cultured and wild species. In the course of a project to isolate the nematode resistance genes by strategies of reverse genetics, probes were cloned from DNA of a fragmented B. procumbens chromosome carrying a resistance gene, which had been isolated by pulsed-field gel electrophoresis. One probe (pRK643) hybridized with a short dispersed repetitive DNA element, which was found only in wild beets, and thus may be used as a molecular marker for nematode resistance to progeneis of monosomic addition lines segregating resistant and susceptible individuals. Additional probes for the resistance gene region were obtained with a polymerase chain reaction (PCR)-based strategy using repetitive primers to amplify DNA located between repetitive elements. One of these probes established the existence of at least six different chromosomes from wild beet species, each conferring resistance independently of the others. A strict correlation between the length of the wild beet chromatin introduced in fragment addition and translocation lines and the repeat copy number has been used physically to map the region conferring resistance to a chromosome segment of 0.5-3 Mb.

  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. 75 FR 62404 - Agency Information Collection Activities; Proposed Collection; Comment Request; Additional...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-08

    ...-counter (OTC) drugs as generally recognized as safe and effective and not misbranded. DATES: Submit either... additional criteria and procedures for classifying OTC drugs as generally recognized as safe and effective and not misbranded (2002 TEA final rule). The regulations in Sec. 330.14 state that OTC drug...

  18. Synthesis and antibacterial evaluation of novel 4″-glycyl linked quinolyl-azithromycins with potent activity against macrolide-resistant pathogens.

    PubMed

    Pavlović, Dražen; Mutak, Stjepan

    2016-03-15

    A new azithromycin-based series of antibacterial macrolones is reported, which features the use of a 4″-ester linked glycin for tethering the quinolone side chain to the macrolide scaffold. Among the analogs prepared, compounds 9e and 22f with a quinolon-6-yl moiety were found to have potent and well-balanced activity against clinically important respiratory tract pathogens, including erythromycin-susceptible and MLSB resistant strains of Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae. In addition, potential lead compounds 9e and 22f demonstrated outstanding levels of activity against Moraxella catarrhalis and inducibly MLSB resistant Staphylococcus aureus. The best member of this series 22f rivals or exceeds, in potency, some of the most active ketolide antibacterial agents known today, such as telithromycin and cethromycin. PMID:26860929

  19. Synthesis and antibacterial evaluation of novel 4″-glycyl linked quinolyl-azithromycins with potent activity against macrolide-resistant pathogens.

    PubMed

    Pavlović, Dražen; Mutak, Stjepan

    2016-03-15

    A new azithromycin-based series of antibacterial macrolones is reported, which features the use of a 4″-ester linked glycin for tethering the quinolone side chain to the macrolide scaffold. Among the analogs prepared, compounds 9e and 22f with a quinolon-6-yl moiety were found to have potent and well-balanced activity against clinically important respiratory tract pathogens, including erythromycin-susceptible and MLSB resistant strains of Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae. In addition, potential lead compounds 9e and 22f demonstrated outstanding levels of activity against Moraxella catarrhalis and inducibly MLSB resistant Staphylococcus aureus. The best member of this series 22f rivals or exceeds, in potency, some of the most active ketolide antibacterial agents known today, such as telithromycin and cethromycin.

  20. 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. PMID:27318162

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

    DOE PAGES

    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 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

  2. 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.

  3. 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. PMID:23703544

  4. Higher Physical Activity Is Associated With Lower Aortic Stiffness but Not With Central Blood Pressure: The ADDITION-Pro Study

    PubMed Central

    Laursen, Anne Sofie Dam; Hansen, Anne-Louise Smidt; Wiinberg, Niels; Brage, Søren; Sandbæk, Annelli; Lauritzen, Torsten; Witte, Daniel R.; Jørgensen, Marit Eika; Johansen, Nanna Borup

    2015-01-01

    Abstract Physical activity is associated with reduced cardiovascular disease risk. However, improvements in conventional risk factors due to physical activity do not explain its full benefit. Therefore, we examined associations of objectively measured physical activity energy expenditure and intensity with central hemodynamics to provide new insight into the link between physical activity and cardiovascular disease. We analyzed data from 1816 Danes (median age: 66 years) without cardiovascular disease. Physical activity was estimated using combined accelerometry and heart rate monitoring. Aortic stiffness was assessed by applanation tonometry, as aortic pulse wave velocity, and central blood pressure was estimated from radial waveforms. Associations between physical activity energy expenditure and central hemodynamics were examined by linear regression. Furthermore, the consequence of substituting 1 hour sedentary behavior with 1 hour light or moderate-to-vigorous physical activity on central hemodynamics was examined. Median physical activity energy expenditure was 28.0 kJ/kg/d (IQR: 19.8; 38.7). A 10 kJ/kg/d higher energy expenditure was associated with 0.75% lower aortic pulse wave velocity (CI: −1.47; −0.03). Associations with central systolic blood pressure and central pulse pressure were not statistically significant. We observed no difference in central hemodynamics when substituting 1 hour sedentary behavior with 1 hour light or moderate-to-vigorous physical activity. In this relatively inactive population, higher physical activity energy expenditure was associated with lower aortic stiffness, while there was no statistically significant association between substitution of activity intensity and central hemodynamics. This suggests that lower aortic stiffness is one of a number of health benefits attributed to higher habitual physical activity. PMID:25654392

  5. Aggregation of Cricket Activity in Response to Resource Addition Increases Local Diversity

    PubMed Central

    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. PMID:26436669

  6. 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.

  7. Transglutaminase cross-linking effect on sensory characteristics and antioxidant activities of Maillard reaction products from soybean protein hydrolysates.

    PubMed

    Song, Na; Tan, Chen; Huang, Meigui; Liu, Ping; Eric, Karangwa; Zhang, Xiaoming; Xia, Shuqin; Jia, Chengsheng

    2013-01-01

    To improve the yield of Maillard peptides, a microbial transglutaminase (MTGase) was used to increase the content of 1000-5000Da peptides in soybean protein hydrolysates by using a cross-linking reaction. The sensory characteristics and antioxidant activities of corresponding Maillard Reaction Products (MSPC) was then evaluated. After cross-linking treatment the content of 1000-5000Da peptides in protein hydrolysates and the yield of Maillard peptides increased by 21.19% and 8.71%, respectively, which contributed to the improved mouthfulness of MSPC. The bitter amino acids were significantly decreased and the umami acids were markedly increased in MSPC. Volatile compounds identified by GC-MS analysis showed that the content of the important meaty flavour compounds (such as 2-methyl-3-furanthiol, bis(2-methyl-3-furyl)disulfide) of MSPC were dramatically higher than that of MRPs from uncross-linking peptides. Combined with sensory evaluation, it was confirmed that MTGase cross-linking improved the flavour Characteristics and did not affect the antioxidant activity of MSPC.

  8. Linking Counselor Activities and Students' College Readiness: How They Matter for Disadvantaged Students

    ERIC Educational Resources Information Center

    Fitzpatrick, Daniel; Schneider, Barbara

    2016-01-01

    Students' college readiness has important links with their access to and success in postsecondary education. College readiness measures appear to be malleable based on high school counselors' work. Unfortunately, the research-to-date provides only minimal guidance for what high school counselors should actually do in order to help their students.…

  9. Effect of vitamin C and folic acid on seed vigour response and phenolic-linked antioxidant activity.

    PubMed

    Burguieres, Elizabeth; McCue, Patrick; Kwon, Young-In; Shetty, Kalidas

    2007-05-01

    Folic acid and vitamin C were used in the concentration range of 0-500muM as exogenous growth enhancers to stimulate pea (Pisum sativum) seedling vigour. The results suggest that a concentration of 50muM folic acid and 500muM vitamin C were optimum in maximally enhancing seed vigour and potentially seedling performance according to both agronomic and biochemical seed vigour parameters. Results indicated that germination percentage, shoot weight, shoot height, and root length were enhanced in folic acid and vitamin C treated plants compared to control plants. The levels of enhanced phenolic content in response to folic acid and vitamin C treatments were highest on days 8 and 10. Evaluation of critical biochemical parameters indicated that the average glucose-6-phosphate dehydrogenase (G6PDH) activity and proline content in response to treatments were higher than control and correlated to enhanced phenolic content and DPPH-based antioxidant activity. Key enzymes, guaiacol peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) were also higher in response to treatments and correlated to enhanced phenolic content and DPPH-based antioxidant activity. Taken together, these studies support the hypothesis that the proline-linked pentose phosphate pathway stimulates phenolic synthesis and related free-radical scavenging antioxidant activity. Further, this proline-linked pentose phosphate pathway stimulation in response to folic acid and vitamin C was also correlated to antioxidant enzyme response indicated by the stimulation of GPX, SOD, and CAT activities. Therefore, this study indicates the enhancement of seed vigour response by folic acid and vitamin C as reflected in both agronomic and biochemical responses, and this occurred through the stimulation of phenolic-linked antioxidant response that is likely positively modulated through the proline-linked pentose phosphate pathway.

  10. 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. PMID:26790921

  11. 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...

  12. 15 CFR 922.164 - Additional activity regulations by Sanctuary area.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., breaking, cutting, spearing or similarly injuring any coral or other marine invertebrate, or any plant... injuring any coral, marine invertebrate, fish, bottom formation, algae, seagrass or other living or dead organism, including shells, or attempting any of these activities. However, fish, invertebrates, and...

  13. 15 CFR 922.164 - Additional activity regulations by Sanctuary area.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., breaking, cutting, spearing or similarly injuring any coral or other marine invertebrate, or any plant... injuring any coral, marine invertebrate, fish, bottom formation, algae, seagrass or other living or dead organism, including shells, or attempting any of these activities. However, fish, invertebrates, and...

  14. 15 CFR 922.164 - Additional activity regulations by Sanctuary area.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., breaking, cutting, spearing or similarly injuring any coral or other marine invertebrate, or any plant... injuring any coral, marine invertebrate, fish, bottom formation, algae, seagrass or other living or dead organism, including shells, or attempting any of these activities. However, fish, invertebrates, and...

  15. 15 CFR 922.164 - Additional activity regulations by Sanctuary area.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., breaking, cutting, spearing or similarly injuring any coral or other marine invertebrate, or any plant... injuring any coral, marine invertebrate, fish, bottom formation, algae, seagrass or other living or dead organism, including shells, or attempting any of these activities. However, fish, invertebrates, and...

  16. 15 CFR 922.164 - Additional activity regulations by Sanctuary area.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., breaking, cutting, spearing or similarly injuring any coral or other marine invertebrate, or any plant... injuring any coral, marine invertebrate, fish, bottom formation, algae, seagrass or other living or dead organism, including shells, or attempting any of these activities. However, fish, invertebrates, and...

  17. 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.

  18. Carboxylic Acids as A Traceless Activation Group for Conjugate Additions: A Three-Step Synthesis of (±)-Pregabalin

    PubMed Central

    2015-01-01

    The direct application of carboxylic acids as a traceless activation group for radical Michael additions has been accomplished via visible light-mediated photoredox catalysis. Photon-induced oxidation of a broad series of carboxylic acids, including hydrocarbon-substituted, α-oxy, and α-amino acids, provides a versatile CO2-extrusion platform to generate Michael donors without the requirement for organometallic activation or propagation. A diverse array of Michael acceptors is amenable to this new conjugate addition strategy. An application of this technology to a three-step synthesis of the medicinal agent pregabalin (commercialized by Pfizer under the trade name Lyrica) is also presented. PMID:25032785

  19. Enhanced allergic responsiveness after early childhood infection with respiratory viruses: Are long-lived alternatively activated macrophages the missing link?

    PubMed

    Keegan, Achsah D; Shirey, Kari Ann; Bagdure, Dayanand; Blanco, Jorge; Viscardi, Rose M; Vogel, Stefanie N

    2016-07-01

    Early childhood infection with respiratory viruses, including human rhinovirus, respiratory syncytial virus (RSV) and influenza, is associated with an increased risk of allergic asthma and severe exacerbation of ongoing disease. Despite the long recognition of this relationship, the mechanism linking viral infection and later susceptibility to allergic lung inflammation is still poorly understood. We discuss the literature and provide new evidence demonstrating that these viruses induce the alternative activation of macrophages. Alternatively activated macrophages (AAM) induced by RSV or influenza infection persisted in the lungs of mice up to 90 days after initial viral infection. Several studies suggest that AAM contribute to allergic inflammatory responses, although their mechanism of action is unclear. In this commentary, we propose that virus-induced AAM provide a link between viral infection and enhanced responses to inhaled allergens. PMID:27178560

  20. Linking the Activity Measure for Post-acute Care and the Quality of Life Outcomes in Neurological Disorders

    PubMed Central

    Ni, Pengsheng; Lai, Jin-shei; Tian, Feng; Coster, Wendy J.; Jette, Alan M.; Straub, Donald; Cella, David

    2012-01-01

    Objective To use item response theory (IRT) methods to link physical functioning items in the Activity Measure for Post-acute Care (AM-PAC) and the Quality of Life Outcomes in Neurological Disorders (Neuro-QOL) Design Secondary data analysis of the physical functioning items of AM-PAC and Neuro-QOL. We used a non-equivalent group design with 36 core items common to both instruments. We used a test characteristic curve transformation method to for linking AM-PAC and Neuro-QOL scores. Linking was conducted so that both raw scores and scaled AM-PAC and Neuro-QOL scores (converted-logit scores with mean = 50 and SD = 10) could be compared. Setting AM-PAC items were administered to rehabilitation patients in post-acute care settings. Neuro-QOL items were administered to a community sample of adults via the Internet. Participants The AM-PAC sample consisted of 1,041 post acute care patients; the Neuro-QOL sample was 549 community-dwelling adults. Interventions Not applicable. Main Outcome Measures 25 Mobility items and 11 ADL items common to both instruments were included in the analysis. Results Neuro-QOL items were linked to the AM-PAC scale using the Generalized Partial Credit Model. Mobility and ADL subscale scores from the two instruments were calibrated to the AM-PAC metric. Conclusions An IRT-based linking method placed AM-PAC and NeuroQOL Mobility and ADL scores on a common metric. This linking allowed estimation of AM-PAC Mobility and ADL subscale scores based on Neuro-QOL Mobility and ADL subscale scores, and vice versa. The accuracy of these results should be validated in a future sample in which participants respond to both instruments. PMID:21958921

  1. Cross-linking of T-cell receptors on double-positive thymocytes induces a cytokine-mediated stromal activation process linked to cell death.

    PubMed Central

    Lerner, A; Clayton, L K; Mizoguchi, E; Ghendler, Y; van Ewijk, W; Koyasu, S; Bhan, A K; Reinherz, E L

    1996-01-01

    To investigate molecular events associated with the intrathymic process of negative selection, we established an in vivo system using an anti-CD3 epsilon monoclonal antibody to induce synchronous apoptosis in the thymus of AND T-cell receptor (TCR) transgenic RAG-2-/- mice in a non-selecting haplotype. This model eliminates endogenous negative selection as well as gene activation in the mature thymocyte compartment, offering an ideal source of tester (anti-CD3 epsilon-treated) and driver (untreated) thymus RNA for representational difference analysis (RDA). Fourteen mRNA sequences that are up-regulated in the thymuses of such mice 2-6 h after anti-CD3 epsilon treatment were identified. Surprisingly, the majority of these transcripts were derived from stromal cells rather than the TCR-cross-linked CD4+CD8+TCRlow thymocytes including the macrophage products IL-1, the chemokine Mig and the transcription factor LRG-21. IFN-gamma secretion from the CD4+CD8+TCRlow thymocytes regulates macrophage Mig production. Three other cytokines (IL-4, GM-CSF and TNF-alpha), known to activate a variety of stromal cells, are also induced in the same thymocyte population undergoing apoptosis. Expression of a TNF-alpha-inducible gene, B94, in stromal cells after TCR ligation further supports the notion of cross-talk between thymocytes and stroma. Thus, TCR-triggered immature thymocytes elaborate cytokines which may regulate the delivery of further signals from stromal cells required for apoptosis. Images PMID:8918465

  2. 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

    2016-06-01

    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). PMID:27219645

  3. 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.

  4. Leptin links with plasminogen activator inhibitor-1 in human obesity: the SABPA study.

    PubMed

    Pieterse, Chiné; Schutte, Rudolph; Schutte, Aletta E

    2015-07-01

    The relationship between obesity and the development of cardiovascular disease is well established. However, the underlying mechanisms contributing to vascular disease and increased cardiovascular risk in the obese remain largely unexplored. Since leptin exerts direct vascular effects, we investigated leptin and the relationship thereof with circulating markers of vascular damage, namely plasminogen activator inhibitor-1 antigen (PAI-1(ag)), von Willebrand factor antigen (vWF(ag)) and urinary albumin-to-creatinine ratio (ACR). The study included a bi-ethnic population of 409 African and Caucasian teachers who were stratified into lean (<0.5) and obese (⩾0.5) groups according to waist-to-height ratio. We obtained ambulatory blood pressure measurements and determined serum leptin levels, PAI-1(ag), vWF(ag) and ACR, as markers of vascular damage. The obese group had higher leptin (P<0.001) and PAI-1(ag) (P<0.001) levels and a tendency existed for higher vWF(ag) (P=0.068). ACR did not differ between the two groups (P=0.21). In single regression analyses positive associations existed between leptin and all markers of vascular damage (all P<0.001) only in the obese group. After adjusting for covariates and confounders in multiple regression analyses, only the association between leptin and PAI-1(ag) remained (R(2)=0.440; β=0.293; P=0.0021). After adjusting for gender, ethnicity and age, additional analyses indicated that leptin also associated with fibrinogen and clot lysis time in both lean and obese groups, which in turn is associated with 24- h blood pressure and pulse pressure. This result provides evidence that elevated circulating leptin may directly contribute to vascular damage, possibly through mechanism related to thrombotic vascular disease.

  5. Leptin links with plasminogen activator inhibitor-1 in human obesity: the SABPA study.

    PubMed

    Pieterse, Chiné; Schutte, Rudolph; Schutte, Aletta E

    2015-07-01

    The relationship between obesity and the development of cardiovascular disease is well established. However, the underlying mechanisms contributing to vascular disease and increased cardiovascular risk in the obese remain largely unexplored. Since leptin exerts direct vascular effects, we investigated leptin and the relationship thereof with circulating markers of vascular damage, namely plasminogen activator inhibitor-1 antigen (PAI-1(ag)), von Willebrand factor antigen (vWF(ag)) and urinary albumin-to-creatinine ratio (ACR). The study included a bi-ethnic population of 409 African and Caucasian teachers who were stratified into lean (<0.5) and obese (⩾0.5) groups according to waist-to-height ratio. We obtained ambulatory blood pressure measurements and determined serum leptin levels, PAI-1(ag), vWF(ag) and ACR, as markers of vascular damage. The obese group had higher leptin (P<0.001) and PAI-1(ag) (P<0.001) levels and a tendency existed for higher vWF(ag) (P=0.068). ACR did not differ between the two groups (P=0.21). In single regression analyses positive associations existed between leptin and all markers of vascular damage (all P<0.001) only in the obese group. After adjusting for covariates and confounders in multiple regression analyses, only the association between leptin and PAI-1(ag) remained (R(2)=0.440; β=0.293; P=0.0021). After adjusting for gender, ethnicity and age, additional analyses indicated that leptin also associated with fibrinogen and clot lysis time in both lean and obese groups, which in turn is associated with 24- h blood pressure and pulse pressure. This result provides evidence that elevated circulating leptin may directly contribute to vascular damage, possibly through mechanism related to thrombotic vascular disease. PMID:25740294

  6. Striatal activation as a neural link between cognitive and perceptual flexibility.

    PubMed

    Sekutowicz, Maria; Schmack, Katharina; Steimke, Rosa; Paschke, Lena; Sterzer, Philipp; Walter, Henrik; Stelzel, Christine

    2016-11-01

    Our brain continuously evaluates different perceptual interpretations of the available sensory data in order to enable flexible updates of conscious experience. Individuals' perceptual flexibility can be assessed using ambiguous stimuli that cause our perception to continuously switch between two mutually exclusive interpretations. Neural processes underlying perceptual switching are thought to involve the visual cortex, but also non-sensory brain circuits that have been implicated in cognitive processes, such as frontal and parietal regions. Perceptual flexibility varies strongly between individuals and has been related to dopaminergic neurotransmission. Likewise, there is also considerable individual variability in tasks that require flexibility in cognition, and dopamine-dependent striato-frontal signals have been associated with processes promoting cognitive flexibility. Given the anatomical and neurochemical similarities with regard to perceptual and cognitive flexibility, we here probed whether individual differences in perceptual flexibility during bistable perception are related to individual cognitive flexibility associated neural correlates. 126 healthy individuals performed rule-based task switching during functional magnetic resonance imaging (fMRI) and reported perceptual switching during the viewing of a modified version of the Necker cube. Mean phase duration as measure of perceptual flexibility correlated with task-switching associated activity in the right putamen as part of the basal ganglia. In addition, we found a tentative correlation between perceptual and cognitive flexibility. These results indicate that individual differences in cognitive flexibility and associated fronto-striatal processing contribute to differences in perceptual flexibility. Our findings thus provide empirical support for the general notion of shared mechanisms between perception and cognition.

  7. Cdc42p and Rho1p are sequentially activated and mechanistically linked to vacuole membrane fusion

    SciTech Connect

    Logan, Michael R.; Jones, Lynden; Eitzen, Gary

    2010-03-26

    Small monomeric GTPases act as molecular switches, regulating many biological functions via activation of membrane localized signaling cascades. Activation of their switch function is controlled by GTP binding and hydrolysis. Two Rho GTPases, Cdc42p and Rho1p, are localized to the yeast vacuole where they regulate membrane fusion. Here, we define a method to directly examine vacuole membrane Cdc42p and Rho1p activation based on their affinity to probes derived from effectors. Cdc42p and Rho1p showed unique temporal activation which aligned with distinct subreactions of in vitro vacuole fusion. Cdc42p was rapidly activated in an ATP-independent manner while Rho1p activation was kinetically slower and required ATP. Inhibitors that are known to block vacuole membrane fusion were examined for their effect on Cdc42p and Rho1p activation. Rdi1p, which inhibits the dissociation of GDP from Rho proteins, blocked both Cdc42p and Rho1p activation. Ligands of PI(4,5)P{sub 2} specifically inhibited Rho1p activation while pre-incubation with U73122, which targets Plc1p function, increased Rho1p activation. These results define unique activation mechanisms for Cdc42p and Rho1p, which may be linked to the vacuole membrane fusion mechanism.

  8. 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 ...

  9. 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…

  10. 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. PMID:26908655

  11. 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

  12. The Impact of Additional Weekdays of Active Commuting to School on Children Achieving a Criterion of 300+ Minutes of Moderate-to-Vigorous Physical Activity

    ERIC Educational Resources Information Center

    Daly-Smith, Andy J. W.; McKenna, Jim; Radley, Duncan; Long, Jonathan

    2011-01-01

    Objective: To investigate the value of additional days of active commuting for meeting a criterion of 300+ minutes of moderate-to-vigorous physical activity (MVPA; 60+ mins/day x 5) during the school week. Methods: Based on seven-day diaries supported by teachers, binary logistic regression analyses were used to predict achievement of MVPA…

  13. 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

  14. Amino acid addition to Vibrio cholerae LPS establishes a link between surface remodeling in Gram-positive and Gram-negative bacteria

    PubMed Central

    Hankins, Jessica V.; Madsen, James A.; Giles, David K.; Brodbelt, Jennifer S.; Trent, M. Stephen

    2012-01-01

    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. PMID:22589301

  15. Placental cadmium as an additional noninvasive bioindicator of active maternal tobacco smoking.

    PubMed

    Piasek, Martina; Jurasović, Jasna; Sekovanić, Ankica; Brajenović, Nataša; Brčić Karačonji, Irena; Mikolić, Anja; Grgec, Antonija Sulimanec; Stasenko, Sandra

    2016-01-01

    Tobacco smoke (TS) is a mixture of chemicals that is known to exert carcinogenic and endocrine-disrupting effects, as well as adverse effects on various systems. In TS nicotine is the major alkaloid and cadmium (Cd) the most abundant metal ion. The aim of this investigation was to assess exposure to Cd attributed to TS in healthy postpartum subjects (mean age 28 years) after term vaginal delivery in a clinical hospital by determining metal levels in maternal blood, placenta, and cord blood in relation to nicotine in maternal hair (12-cm-long samples). Two study groups were compared based upon self-reporting data: smokers (n = 32; continual cigarette smoking 3 months before and 9 months during pregnancy) and nonsmokers (n = 54; including passive smokers whose parameters did not differ from unexposed nonsmokers). In smokers compared to nonsmokers maternal hair nicotine concentrations increased approximately sevenfold, while Cd levels rose fourfold in maternal blood and up to twofold in placenta. Significant positive correlations were noted between maternal hair nicotine and placental Cd, maternal hair nicotine and maternal blood Cd, and placental Cd and maternal blood Cd. Levels of cord blood Cd were low in both study groups (<0.1 ng/ml). Data indicate that Cd in placenta may serve as a noninvasive bioindicator in addition to commonly used noninvasive hair nicotine in maternal TS assessment, especially in cases where unavailable or inappropriate (short or chemically treated) hair samples occur. PMID:27210017

  16. Placental cadmium as an additional noninvasive bioindicator of active maternal tobacco smoking.

    PubMed

    Piasek, Martina; Jurasović, Jasna; Sekovanić, Ankica; Brajenović, Nataša; Brčić Karačonji, Irena; Mikolić, Anja; Grgec, Antonija Sulimanec; Stasenko, Sandra

    2016-01-01

    Tobacco smoke (TS) is a mixture of chemicals that is known to exert carcinogenic and endocrine-disrupting effects, as well as adverse effects on various systems. In TS nicotine is the major alkaloid and cadmium (Cd) the most abundant metal ion. The aim of this investigation was to assess exposure to Cd attributed to TS in healthy postpartum subjects (mean age 28 years) after term vaginal delivery in a clinical hospital by determining metal levels in maternal blood, placenta, and cord blood in relation to nicotine in maternal hair (12-cm-long samples). Two study groups were compared based upon self-reporting data: smokers (n = 32; continual cigarette smoking 3 months before and 9 months during pregnancy) and nonsmokers (n = 54; including passive smokers whose parameters did not differ from unexposed nonsmokers). In smokers compared to nonsmokers maternal hair nicotine concentrations increased approximately sevenfold, while Cd levels rose fourfold in maternal blood and up to twofold in placenta. Significant positive correlations were noted between maternal hair nicotine and placental Cd, maternal hair nicotine and maternal blood Cd, and placental Cd and maternal blood Cd. Levels of cord blood Cd were low in both study groups (<0.1 ng/ml). Data indicate that Cd in placenta may serve as a noninvasive bioindicator in addition to commonly used noninvasive hair nicotine in maternal TS assessment, especially in cases where unavailable or inappropriate (short or chemically treated) hair samples occur.

  17. 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.

  18. Recent Geological and Hydrological Activity in Amazonis and Elysium Basins and Their Link, Marte Valles (AME): Prime Target for Future Reconnaissance

    NASA Astrophysics Data System (ADS)

    Dohm, J. M.; Robbins, S. J.; Hynek, B. M.

    2012-03-01

    Amazonis and Elysium basins and their link, Marte Vallis (AME), uniquely point to a geologically and hydrologically active Mars. We will present evidence for why AME reconnaissance can help address whether Mars is geologically, hydrologically, and biologically active.

  19. Initial evidence for the link between activities and health: Associations between a balance of activities, functioning and serum levels of cytokines and C-reactive protein.

    PubMed

    Dür, Mona; Steiner, Günter; Stoffer, Michaela Alexandra; Fialka-Moser, Veronika; Kautzky-Willer, Alexandra; Dejaco, Clemens; Ekmekcioglu, Cem; Prodinger, Birgit; Binder, Alexa; Smolen, Josef; Stamm, Tanja Alexandra

    2016-03-01

    Growing evidence shows interrelations of psychological factors, neurological and immunological processes. Therefore, constructs like a balance of activities, the so called "occupational balance", could also have biological correlates. The aim of this study was to investigate potential associations between occupational balance, functioning, cytokines and C-reactive protein (CRP) in patients suffering from a chronic inflammatory disease like rheumatoid arthritis (RA) and healthy people. Moreover, we wanted to explore potential differences in gender and employment status. A descriptive study in patients with RA and healthy people was conducted using the Occupational Balance-Questionnaire (OB-Quest) and the Short-Form 36 Health Survey (SF-36). Serum levels of cytokines, such as interleukin 6 (IL-6) and 8 (IL-8), interferon alpha (INFα), tumour necrosis factor alpha (TNFα), rheumatoid factor (RF) and of CRP were measured. Descriptive statistics, as well as Mann-Whitney U tests and Spearmen's rank correlation coefficients (rs) were calculated. One-hundred-thirty-two patients with RA and 76 healthy people participated. Occupational balance was associated with functioning, cytokines and CRP. The strongest associations were identified in the unemployed healthy-people sample with cytokines and CRP being within the normal range. For example, the OB-Quest item challenging activities was associated with IL-8 (rs=-0.63, p=0.04) and the SF-36 sub-scale bodily pain was associated with IFNα (rs=-0.69, p=0.02). The items rest and sleep (rs=-0.71, p=0.01) and variety of different activities (rs=-0.74, p<0.01) correlated with the SF-36 sub-scale social functioning. Employed and unemployed people differed in their age and CRP levels. Additionally, gender differences were found in two OB-Quest items in that fewer women were able to adapt their activities to changing living conditions and fewer men were overstressed. In conclusion, we found preliminary biological evidence for the link

  20. Initial evidence for the link between activities and health: Associations between a balance of activities, functioning and serum levels of cytokines and C-reactive protein.

    PubMed

    Dür, Mona; Steiner, Günter; Stoffer, Michaela Alexandra; Fialka-Moser, Veronika; Kautzky-Willer, Alexandra; Dejaco, Clemens; Ekmekcioglu, Cem; Prodinger, Birgit; Binder, Alexa; Smolen, Josef; Stamm, Tanja Alexandra

    2016-03-01

    Growing evidence shows interrelations of psychological factors, neurological and immunological processes. Therefore, constructs like a balance of activities, the so called "occupational balance", could also have biological correlates. The aim of this study was to investigate potential associations between occupational balance, functioning, cytokines and C-reactive protein (CRP) in patients suffering from a chronic inflammatory disease like rheumatoid arthritis (RA) and healthy people. Moreover, we wanted to explore potential differences in gender and employment status. A descriptive study in patients with RA and healthy people was conducted using the Occupational Balance-Questionnaire (OB-Quest) and the Short-Form 36 Health Survey (SF-36). Serum levels of cytokines, such as interleukin 6 (IL-6) and 8 (IL-8), interferon alpha (INFα), tumour necrosis factor alpha (TNFα), rheumatoid factor (RF) and of CRP were measured. Descriptive statistics, as well as Mann-Whitney U tests and Spearmen's rank correlation coefficients (rs) were calculated. One-hundred-thirty-two patients with RA and 76 healthy people participated. Occupational balance was associated with functioning, cytokines and CRP. The strongest associations were identified in the unemployed healthy-people sample with cytokines and CRP being within the normal range. For example, the OB-Quest item challenging activities was associated with IL-8 (rs=-0.63, p=0.04) and the SF-36 sub-scale bodily pain was associated with IFNα (rs=-0.69, p=0.02). The items rest and sleep (rs=-0.71, p=0.01) and variety of different activities (rs=-0.74, p<0.01) correlated with the SF-36 sub-scale social functioning. Employed and unemployed people differed in their age and CRP levels. Additionally, gender differences were found in two OB-Quest items in that fewer women were able to adapt their activities to changing living conditions and fewer men were overstressed. In conclusion, we found preliminary biological evidence for the link

  1. Alteration of extracellular enzyme activity and microbial abundance by biochar addition: Implication for carbon sequestration in subtropical mangrove sediment.

    PubMed

    Luo, Ling; Gu, Ji-Dong

    2016-11-01

    Biochar has attracted more and more attention due to its essential role in adsorbing pollutants, improving soil fertility, and modifying greenhouse gas emission. However, the influences of biochar on extracellular enzyme activity and microbial abundance are still lack and debatable. Currently, there is no information about the impact of biochar on the function of mangrove ecosystems. Therefore, we explored the effects of biochar on extracellular enzyme activity and microbial abundance in subtropical mangrove sediment, and further estimated the contribution of biochar to C sequestration. In this study, sediments were amended with 0 (control), 0.5, 1.0 and 2.0% of biochar and incubated at 25 °C for 90 days. After incubation, enzyme activities, microbial abundance and the increased percentage of sediment organic C content were determined. Both increase (phenol oxidase and β-glucosidase) and decrease (peroxidase, N-acetyl-glucosaminidase and acid phosphatase) of enzyme activities were observed in biochar treatments, but only peroxidase activity showed statistical significance (at least p < 0.01) compared to the control. Moreover, the activities of all enzymes tested were significantly related to the content of biochar addition (at least p < 0.05). On the other hand, bacterial and fungal abundance in biochar treatments were remarkably lower than control (p < 0.001), and the significantly negative relationship (p < 0.05) between bacterial abundance and the content of biochar was found. Additionally, the increased percentage of organic C gradually increased with biochar addition rate, which provided evidence for applying biochar to mitigate climate change. Given the importance of microorganisms and enzyme activities in sediment organic matter decomposition, the increased C sequestration might be explained by the large decrease of microbial abundance and enzyme activity after biochar intervention. PMID:27454094

  2. Alteration of extracellular enzyme activity and microbial abundance by biochar addition: Implication for carbon sequestration in subtropical mangrove sediment.

    PubMed

    Luo, Ling; Gu, Ji-Dong

    2016-11-01

    Biochar has attracted more and more attention due to its essential role in adsorbing pollutants, improving soil fertility, and modifying greenhouse gas emission. However, the influences of biochar on extracellular enzyme activity and microbial abundance are still lack and debatable. Currently, there is no information about the impact of biochar on the function of mangrove ecosystems. Therefore, we explored the effects of biochar on extracellular enzyme activity and microbial abundance in subtropical mangrove sediment, and further estimated the contribution of biochar to C sequestration. In this study, sediments were amended with 0 (control), 0.5, 1.0 and 2.0% of biochar and incubated at 25 °C for 90 days. After incubation, enzyme activities, microbial abundance and the increased percentage of sediment organic C content were determined. Both increase (phenol oxidase and β-glucosidase) and decrease (peroxidase, N-acetyl-glucosaminidase and acid phosphatase) of enzyme activities were observed in biochar treatments, but only peroxidase activity showed statistical significance (at least p < 0.01) compared to the control. Moreover, the activities of all enzymes tested were significantly related to the content of biochar addition (at least p < 0.05). On the other hand, bacterial and fungal abundance in biochar treatments were remarkably lower than control (p < 0.001), and the significantly negative relationship (p < 0.05) between bacterial abundance and the content of biochar was found. Additionally, the increased percentage of organic C gradually increased with biochar addition rate, which provided evidence for applying biochar to mitigate climate change. Given the importance of microorganisms and enzyme activities in sediment organic matter decomposition, the increased C sequestration might be explained by the large decrease of microbial abundance and enzyme activity after biochar intervention.

  3. 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. PMID:25150685

  4. Additive and Synergistic Bactericidal Activity of Antibodies Directed against Minor Outer Membrane Proteins of Neisseria meningitidis▿

    PubMed Central

    Weynants, Vincent E.; Feron, Christiane M.; Goraj, Karine K.; Bos, Martine P.; Denoël, Philippe A.; Verlant, Vincent G.; Tommassen, Jan; Peak, Ian R. A.; Judd, Ralph C.; Jennings, Michael P.; Poolman, Jan T.

    2007-01-01

    Neisseria meningitidis serogroup B is a major cause of bacterial meningitis in younger populations. The available vaccines are based on outer membrane vesicles obtained from wild-type strains. In children less than 2 years old they confer protection only against strains expressing homologous PorA, a major, variable outer membrane protein (OMP). We genetically modified a strain in order to eliminate PorA and to overproduce one or several minor and conserved OMPs. Using a mouse model mimicking children's PorA-specific bactericidal activity, it was demonstrated that overproduction of more than one minor OMP is required to elicit antibodies able to induce complement-mediated killing of strains expressing heterologous PorA. It is concluded that a critical density of bactericidal antibodies needs to be reached at the surface of meningococci to induce complement-mediated killing. With minor OMPs, this threshold is reached when more than one antigen is targeted, and this allows cross-protection. PMID:17664268

  5. N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias

    PubMed Central

    Soto, Antonio G.; Smith, Thomas H.; Chen, Buxin; Bhattacharya, Supriyo; Cordova, Isabel Canto; Kenakin, Terry; Vaidehi, Nagarajan; Trejo, JoAnn

    2015-01-01

    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. PMID:26100877

  6. 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

    2015-07-01

    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. PMID:26100877

  7. Dissection of the radical reactions linked to fetal hemoglobin reveals enhanced pseudoperoxidase activity

    PubMed Central

    Ratanasopa, Khuanpiroon; Strader, Michael Brad; Alayash, Abdu I.; Bulow, Leif

    2015-01-01

    In the presence of excess hydrogen peroxide (H2O2), ferrous (Fe+2) human hemoglobin (Hb) (α2β2) undergoes a rapid conversion to a higher oxidation ferryl state (Fe+4) which rapidly autoreduces back to the ferric form (Fe+3) as H2O2 is consumed in the reaction. In the presence of additional H2O2 the ferric state can form both ferryl Hb and an associated protein radical in a pseudoperoxidative cycle that results in the loss of radicals and heme degradation. We examined whether adult HbA (β2α2) exhibits a different pseudoenzymatic activity than fetal Hb (γ2α2) due to the switch of γ to β subunits. Rapid mixing of the ferric forms of both proteins with excess H2O2 resulted in biphasic kinetic time courses that can be assigned to γ/β and α, respectively. Although there was a 1.5 fold increase in the fast reacting γ /β subunits the slower reacting phases (attributed to α subunits of both proteins) were essentially the same. However, the rate constant for the auto-reduction of ferryl back to ferric for both proteins was found to be 76% higher for HbF than HbA and in the presence of the mild reducing agent, ascorbate there was a 3-fold higher reduction rate in ferryl HbF as opposed to ferryl HbA. Using quantitative mass spectrometry in the presence of H2O2 we found oxidized γ/β Cys93, to be more abundantly present in HbA than HbF, whereas higher levels of nitrated β Tyr35 containing peptides were found in HbA samples treated with nitrite. The extraordinary stability of HbF reported here may explain the evolutionary advantage this protein may confer onto co-inherited hemoglobinopathies and can also be utilized in the engineering of oxidatively stable Hb-based oxygen carriers. PMID:25750627

  8. 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

  9. Linking Microbial Heterotrophic Activity and Sediment Lithology in Oxic, Oligotrophic Sub-Seafloor Sediments of the North Atlantic Ocean

    PubMed Central

    Picard, Aude; Ferdelman, Timothy G.

    2011-01-01

    Microbial heterotrophic activity was investigated in oxic sub-seafloor sediments at North Pond, a sediment pond situated at 23°N on the western flank of the Mid-Atlantic Ridge. The North Pond sediments underlie the oligotrophic North Atlantic Gyre at 4580-m water depth and cover a 7–8 million-year-old basaltic crust aquifer through which seawater flows. Discrete samples for experimentation were obtained from up to ~9 m-long gravity cores taken at 14 stations in the North Pond area. Potential respiration rates were determined in sediment slurries incubated under aerobic conditions with 14C-acetate. Microbial heterotrophic activity, as defined by oxidation of acetate to CO2 (with O2 as electron acceptor), was detected in all 14 stations and all depths sampled. Potential respiration rates were generally low (<0.2 nmol of respired acetate cm−3 d−1) in the sediment, but indicate that microbial heterotrophic activity occurs in deep-sea, oxic, sub-seafloor sediments. Furthermore, discernable differences in activity existed between sites and within given depth profiles. At seven stations, activity was increased by several orders of magnitude at depth (up to ~12 nmol of acetate respired cm−3 d−1). We attempted to correlate the measures of activity with high-resolution color and element stratigraphy. Increased activities at certain depths may be correlated to variations in the sediment geology, i.e., to the presence of dark clay-rich layers, of sandy layers, or within clay-rich horizons presumably overlying basalts. This would suggest that the distribution of microbial heterotrophic activity in deeply buried sediments may be linked to specific lithologies. Nevertheless, high-resolution microbial examination at the level currently enjoyed by sedimentologists will be required to fully explore this link. PMID:22207869

  10. High performance flexible double-sided micro-supercapacitors with an organic gel electrolyte containing a redox-active additive.

    PubMed

    Kim, Doyeon; Lee, Geumbee; Kim, Daeil; Yun, Junyeong; Lee, Sang-Soo; Ha, Jeong Sook

    2016-08-25

    In this study, we report the fabrication of a high performance flexible micro-supercapacitor (MSC) with an organic gel electrolyte containing a redox-active additive, referred to as poly(methyl methacrylate)-propylene carbonate-lithium perchlorate-hydroquinone (PMMA-PC-LiClO4-HQ). Hexagonal MSCs fabricated on thin polyethylene terephthalate (PET) films had interdigitated electrodes made of spray-coated multi-walled carbon nanotubes (MWNTs) on Au. The addition of HQ as a redox-active additive enhanced not only the specific capacitance but also the energy density of the MSCs dramatically, which is approximately 35 times higher than that of MSCs without the HQ additive. In addition, both areal capacitance and areal energy density could be doubled by fabrication of double-sided MSCs, where two MSCs are connected in parallel. The double-sided MSCs exhibited stable electrochemical performance during repeated deformation by bending. By dry-transferring the double-sided MSCs based on PMMA-PC-LiClO4-HQ on a deformable polymer substrate, we fabricated a stretchable MSC array, which also retained its electrochemical performance during a uniaxial strain of 40%. Furthermore, a wearable energy storage bracelet made of such an MSC array could operate a μ-LED on the wrist. PMID:27511060

  11. A fail safe laser activated switch used as an emergency control link at the Langley Vortex Research Facility

    NASA Technical Reports Server (NTRS)

    Kassel, P. C., Jr.

    1978-01-01

    A fail safe light activated switch was used as an emergency control link at the Langley Vortex Research Facility. In this facility aircraft models were towed through a still air test chamber by a gasoline powered vehicle which was launched from one end of a 427-meter track and attained velocities to 31 m/sec in the test chamber. A 5 mW HeNe laser with a mechanical copper provided a connecting link with the moving tow vehicle on which a silicon photodiode receiver with a specially designed amplifier provided a fail safe switching action. This system provided an emergency means of stopping the vehicle by turning off the laser to interrupt the power to the vehicle ignition and brake release systems.

  12. Effect of One Percent Chlorhexidine Addition on the Antibacterial Activity and Mechanical Properties of Sealants: An in vitro Study

    PubMed Central

    Asokan, Sharath; John, J Baby; Priya, PR Geetha; Devi, Jagadeesan Gnana

    2015-01-01

    ABSTRACT Aim: The aim of the study was to evaluate the effect of addition of 1% chlorhexidine digluconate solution on the antibacterial activity and mechanical properties of glass ionomer and resin based sealant. Materials and methods: Conventional glass ionomer sealant (GIS) (Fuji VII, Japan) and resin sealant (Clinpro 3M ESPE, USA) were used in this study. Chlorhexidine digluconate (CHX) (20%) liquid was added to both the sealants, and the concentration of chlorhexidine in sealants was adjusted to 1%. The sealants were divided into four groups as: group A (GIS), group B (GIS + 1% CHX), group C (resin sealant), group D (resin sealant + 1% CHX). Five cylindrical specimens were prepared in each group. Their antibacterial activity against Streptococcus mutans and Lactobacillus acidophilus, and their mechanical properties (compressive strength and diametrical tensile strength) were assessed. Mann-Whitney and Wilcoxon signed rank test were used appropriately for statistical analysis (SPSS version 19). Result: Addition of one percent chlorhexidine significantly increased the antibacterial activity of both the sealants. There was a significant difference between groups A and B (p < 0.009), and groups C and D (p < 0.008). There was no significant difference in the mechanical properties of the sealants. Conclusion: Addition of one percent chlorhexidine to the glass ionomer and resin based sealants provided sufficient antibacterial activity, without significantly affecting the mechanical property of the sealants. How to cite this article: Shanmugaavel AK, Asokan S, John JB, Geetha Priya PR, Gnana Devi J. Effect of one percent Chlorhexidine Addition on the Antibacterial Activity and Mechanical Properties of Sealants: An in vitro Study. Int J Clin Pediatr Dent 2015;8(3):196-201. PMID:26628854

  13. Does the neighborhood context alter the link between youth's after-school time activities and developmental outcomes? A multilevel analysis.

    PubMed

    Fauth, Rebecca C; Roth, Jodie L; Brooks-Gunn, Jeanne

    2007-05-01

    This article examines links between different measures of after-school time activity participation (5 specific activities and breadth) on youth's developmental outcomes (anxiety/depression, delinquency, and substance use) over 6 years and whether these links are moderated by neighborhood-level variables. The sample (N=1,315) of 9- and 12-year-old youth was drawn from the Project on Human Development in Chicago Neighborhoods (PHDCN), a multilevel, longitudinal study of youth from 80 Chicago neighborhoods. Findings revealed that different types of activities and patterns of participation over time were associated with outcomes for youth and that, to some extent, these outcomes varied with neighborhood characteristics. In brief, sports participation was associated with fewer anxious/depressed symptoms, higher average delinquency scores, and increased substance use-both average scores and growth over time. Participation in the arts and student government were negatively associated with average substance use and attenuated increases in usage over time. Participation in community-based clubs was positively associated with youth's anxiety/depression in violent neighborhoods only, whereas church groups were protective against substance use in nonviolent neighborhoods. The direction of the influence of breadth of participation was nonlinear for delinquency such that delinquency scores were highest among youth who engaged in an average number of activities.

  14. NRBF2 Regulates Autophagy and Prevents Liver Injury by Modulating Atg14L-Linked Phosphatidylinositol-3 Kinase III Activity

    PubMed Central

    Lu, Jiahong; He, Liqiang; Behrends, Christian; Araki, Masatake; Araki, Kimi; Wang, Qing Jun; Catanzaro, Joseph M.; Friedman, Scott L.; Zong, Wei-Xing; Fiel, M. Isabel; Li, Min; Yue, Zhenyu

    2015-01-01

    The Beclin 1-Vps34 complex, the core component of the class III phosphatidylinositol-3 kinase (PI3K-III), binds Atg14L or UVRAG to control different steps of autophagy. However, the mechanism underlying the control of PI3K-III activity remains elusive. Here we report the identification of NRBF2 as a component in the specific PI3K-III complex and a modulator of PI3K-III activity. Through its MIT domain, NRBF2 binds Atg14L directly and enhances Atg14L-linked Vps34 kinase activity and autophagy induction. NRBF2 deficient cells exhibit enhanced vulnerability to ER stress that is reversed by re-introducing exogenous NRBF2. NRBF2 deficient mice develop focal liver necrosis and ductular reaction, accompanied by impaired Atg14L-linked Vps34 activity and autophagy, though the mice show no increased mortality. Our data reveals a key role for NRBF2 in the assembly of the specific Atg14L-Beclin 1-Vps34-Vps15 complex for autophagy induction. Thus, NRBF2 modulates autophagy via regulation of PI3K-III and prevents ER stress-mediated cytotoxicity and liver injury. PMID:24849286

  15. 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

  16. 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

  17. Characterization and catalytic activity of covalently linked bipyridyl ruthenium OXO dimers

    SciTech Connect

    Petach, H.H.; Elliott, C.M. . Dept. of Chemistry)

    1992-08-01

    This paper reports that covalently linked bipyridyl ligands (L-L) with alkyl linkages varying from (-CH[sub 2]-)[sub 2] to (-CH[sub 2]-)[sub 12] were used to prepare ruthenium oxo dimers of the form [bpy (H[sub 2]O)RuO(L-L)Ru(H[sub 2]O) (bpy)][sup 4+]. The bridging alkyl linkage increased the stability of these oxo dimers by maintaining the relative proximity of the two ruthenium centers even when the oxo bridge is cleaved. These complexes have been characterized by electronic spectroscopy and electrochemistry. The electrochemistry in CH[sub 3]CN/0.1M TBAP exhibits a reversible one-electron oxidation followed by a second reversible two-electron oxidation which becomes catalytic in aqueous solution. The catalytic generation of dioxygen from water was observed upon bulk electrolysis of the oxo dimer at + 1.39 V.

  18. Physical activity and memory functions: are neurotrophins and cerebral gray matter volume the missing link?

    PubMed

    Flöel, A; Ruscheweyh, R; Krüger, K; Willemer, C; Winter, B; Völker, K; Lohmann, H; Zitzmann, M; Mooren, F; Breitenstein, C; Knecht, S

    2010-02-01

    Epidemiological studies reveal better cognitive function in physically active individuals. Possible mediators for this effect are neurotrophins, which are up-regulated through physical exercise and induce neuronal growth and synaptogenesis in the animal model. Here we cross-sectionally assessed 75 healthy older individuals for levels of physical activity, aerobic fitness, and memory encoding, as well as neurotrophin levels and cerebral gray matter volume. We found that physical activity, but not cardiovascular fitness, was associated with better memory encoding after controlling for age, sex, education, depression, alcohol consumption, and smoking. Higher levels of physical activity were associated with higher levels of the neurotrophin granulocyte colony stimulating factor (G-CSF) and increased cerebral gray matter volume in prefrontal and cingulate cortex as assessed by magnetic resonance voxel-based morphometry. While mediating factors will need to be further elucidated, these findings indicate that even low-level physical activity exerts beneficial effects on memory functions in older individuals.

  19. 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.

  20. 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.

  1. Structural basis for the requirement of additional factors for MLL1 SET domain activity and recognition of epigenetic marks.

    PubMed

    Southall, Stacey M; Wong, Poon-Sheng; Odho, Zain; Roe, S Mark; Wilson, Jon R

    2009-01-30

    The mixed-lineage leukemia protein MLL1 is a transcriptional regulator with an essential role in early development and hematopoiesis. The biological function of MLL1 is mediated by the histone H3K4 methyltransferase activity of the carboxyl-terminal SET domain. We have determined the crystal structure of the MLL1 SET domain in complex with cofactor product AdoHcy and a histone H3 peptide. This structure indicates that, in order to form a well-ordered active site, a highly variable but essential component of the SET domain must be repositioned. To test this idea, we compared the effect of the addition of MLL complex members on methyltransferase activity and show that both RbBP5 and Ash2L but not Wdr5 stimulate activity. Additionally, we have determined the effect of posttranslational modifications on histone H3 residues downstream and upstream from the target lysine and provide a structural explanation for why H3T3 phosphorylation and H3K9 acetylation regulate activity. PMID:19187761

  2. Detection of interleukin-2 in addition to interferon-gamma discriminates active tuberculosis patients, latently infected individuals, and controls.

    PubMed

    Biselli, R; Mariotti, S; Sargentini, V; Sauzullo, I; Lastilla, M; Mengoni, F; Vanini, V; Girardi, E; Goletti, D; D' Amelio, R; Nisini, R

    2010-08-01

    Effective control of tuberculosis (TB) includes discrimination of subjects with active TB from individuals with latent TB infection (LTBI). As distinct interferon (IFN)-gamma and interleukin (IL)-2 profiles of antigen-specific T-cells have been associated with different clinical stages and antigen loads in several viral and bacterial diseases, we analysed these cytokines in TB using a modified QuantiFERON-TB Gold In Tube test. Detection of IL-2 in addition to IFN-gamma distinguishes not only Mycobacterium tuberculosis-infected subjects from healthy controls, but also individuals with LTBI from active TB patients. This may help to improve diagnostic tests for TB.

  3. Lipase catalysis and thiol-Michael addition: a relevant association for the synthesis of new surface-active carbohydrate esters.

    PubMed

    Boyère, Cédric; Favrelle, Audrey; Broze, Guy; Laurent, Pascal; Nott, Katherine; Paquot, Michel; Blecker, Christophe; Jérôme, Christine; Debuigne, Antoine

    2011-10-18

    A novel class of surface-active carbohydrate esters is prepared by a two-step strategy that takes advantage of the selectivity of enzymatic catalysis and the versatility of the thiol-Michael addition reaction. The surfactant performance of the produced aliphatic, fluorinated and silicon based sugar esters are evaluated by surface tension measurements. The novel thiolated mannose, made available in this work, appears as a powerful building block for the incorporation of unprotected sugar moieties into complex molecules.

  4. 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.

  5. Evidence for protein kinase C-dependent and -independent activation of mitogen-activated protein kinase in T cells: potential role of additional diacylglycerol binding proteins.

    PubMed

    Puente, L G; Stone, J C; Ostergaard, H L

    2000-12-15

    Activation of mitogen-activated protein kinases (MAPK) is a critical signal transduction event for CTL activation, but the signaling mechanisms responsible are not fully characterized. Protein kinase C (PKC) is thought to contribute to MAPK activation following TCR stimulation. We have found that dependence on PKC varies with the method used to stimulate the T cells. Extracellular signal-regulated kinase (ERK) activation in CTL stimulated with soluble cross-linked anti-CD3 is completely inhibited by the PKC inhibitor bisindolylmaleimide (BIM). In contrast, only the later time points in the course of ERK activation are sensitive to BIM when CTL are stimulated with immobilized anti-CD3, a condition that stimulates CTL degranulation. Surprisingly, MAPK activation in response to immobilized anti-CD3 is strongly inhibited at all time points by the diacylglycerol (DAG)-binding domain inhibitor calphostin C implicating the contribution of a DAG-dependent but PKC-independent pathway in the activation of ERK in CTL clones. Chronic exposure to phorbol ester down-regulates the expression of DAG-responsive PKC isoforms; however, this treatment of CTL clones does not inhibit anti-CD3-induced activation of MAPK. Phorbol ester-treated cells have reduced expression of several isoforms of PKC but still express the recently described DAG-binding Ras guanylnucleotide-releasing protein. These results indicate that the late phase of MAPK activation in CTL clones in response to immobilized anti-CD3 stimulation requires PKC while the early phase requires a DAG-dependent, BIM-resistant component.

  6. CASK stabilizes neurexin and links it to liprin-α in a neuronal activity-dependent manner.

    PubMed

    LaConte, Leslie E W; Chavan, Vrushali; Liang, Chen; Willis, Jeffery; Schönhense, Eva-Maria; Schoch, Susanne; Mukherjee, Konark

    2016-09-01

    CASK, a MAGUK family protein, is an essential protein present in the presynaptic compartment. CASK's cellular role is unknown, but it interacts with multiple proteins important for synapse formation and function, including neurexin, liprin-α, and Mint1. CASK phosphorylates neurexin in a divalent ion-sensitive manner, although the functional relevance of this activity is unclear. Here we find that liprin-α and Mint1 compete for direct binding to CASK, but neurexin1β eliminates this competition, and all four proteins form a complex. We describe a novel mode of interaction between liprin-α and CASK when CASK is bound to neurexin1β. We show that CASK phosphorylates neurexin, modulating the interaction of liprin-α with the CASK-neurexin1β-Mint1 complex. Thus, CASK creates a regulatory and structural link between the presynaptic adhesion molecule neurexin and active zone organizer, liprin-α. In neuronal culture, CASK appears to regulate the stability of neurexin by linking it with this multi-protein presynaptic active zone complex.

  7. The actin-microtubule cross-linking activity of Drosophila Short stop is regulated by intramolecular inhibition.

    PubMed

    Applewhite, Derek A; Grode, Kyle D; Duncan, Mara C; Rogers, Stephen L

    2013-09-01

    Actin and microtubule dynamics must be precisely coordinated during cell migration, mitosis, and morphogenesis--much of this coordination is mediated by proteins that physically bridge the two cytoskeletal networks. We have investigated the regulation of the Drosophila actin-microtubule cross-linker Short stop (Shot), a member of the spectraplakin family. Our data suggest that Shot's cytoskeletal cross-linking activity is regulated by an intramolecular inhibitory mechanism. In its inactive conformation, Shot adopts a "closed" conformation through interactions between its NH(2)-terminal actin-binding domain and COOH-terminal EF-hand-GAS2 domain. This inactive conformation is targeted to the growing microtubule plus end by EB1. On activation, Shot binds along the microtubule through its COOH-terminal GAS2 domain and binds to actin with its NH(2)-terminal tandem CH domains. We propose that this mechanism allows Shot to rapidly cross-link dynamic microtubules in response to localized activating signals at the cell cortex.

  8. 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.

  9. Immune activity elevates energy expenditure of house sparrows: a link between direct and indirect costs?

    PubMed Central

    Martin, Lynn B; Scheuerlein, Alex; Wikelski, Martin

    2003-01-01

    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. PMID:12590753

  10. 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.

  11. 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.

  12. Linking environmental variability and fish performance: integration through the concept of scope for activity.

    PubMed

    Claireaux, Guy; Lefrançois, Christel

    2007-11-29

    Investigating the biological mechanisms linking environmental variability to fish production systems requires the disentangling of the interactions between habitat, environmental adaptation and fitness. Since the number of environmental variables and regulatory processes is large, straightening out the environmental influences on fish performance is intractable unless the mechanistic analysis of the 'fish-milieu' system is preceded by an understanding of the properties of that system. While revisiting the key points in our currently poorly integrated understanding of fish ecophysiology, we have highlighted the explanatory potential contained within Fry's (Fry 1947 Univ. Toronto Stud. Biol. Ser. 55, 1-62) concept of metabolic scope and categorization of environmental factors. These two notions constitute a pair of powerful tools for conducting an external (at the emerging property level) analysis of the environmental influences on fish, as well as an internal (mechanistic) examination of the behavioural, morphological and physiological processes involved. Using examples from our own and others work, we have tried to demonstrate that Fry's framework represents a valuable conceptual basis leading to a broad range of testable ecophysiological hypotheses.

  13. Beta-carotene suppression of benzophenone-sensitized lipid peroxidation in hexane through additional chain-breaking activities

    NASA Astrophysics Data System (ADS)

    Cvetković, Dragan; Marković, Dejan

    2011-01-01

    The aim of this work is to estimate the antioxidant activity of β-carotene in the presence of two different mixtures of phospholipids in hexane solution, under continuous UV-irradiation from three different ranges (UV-A, UV-B, and UV-C). β-Carotene is employed to control lipid peroxidation process generated by UV-irradiation, in the presence and in the absence of selected photosensitizer, benzophenone, by scavenging the involved, created free radicals. The results show that β-carotene undergoes to a substantial, probably structural dependent destruction (bleaching), highly dependent on UV-photons energy input, more expressed in the presence than in the absence of benzophenone. The additional bleaching is synchronized with the further increase in β-carotene antioxidant activity in the presence of benzophenone, implying the same cause: increase in (phospholipids peroxidation) chain-breaking activities.

  14. Synthesis and pharmacological screening for muscle relaxant, anticonvulsant, and sedative activities of certain organic compounds produced by Michael addition.

    PubMed

    Said, Makarem M; Ahmed, Amany A E; El-Alfy, Abir T

    2004-12-01

    Michael addition of certain nucleophiles on alpha, beta-unsaturated ketones 1 led to the formation of adducts 2-7 as well as the reaction of arylidene derivatives with secondary amines afforded the amino compounds 9 and 11. Also, dialkylmalonates were treated with alpha-cyano cinnamide to afford 13. On the other hand, double Michael cycloaddition of ethylcyanoacetate or tetrachlorophthalic anhydride to the suitable divinylketone were synthesized to produce 15-17. Selected compounds (13 and 6) were screened for muscle relaxant, anticonvulsant, and sedative activities using established pharmacological models. Their activities were compared with that of phenobarbital sodium taken as standard. Compound 6 was the most potent muscle relaxant while compounds 13a and 13c offered the highest anticonvulsant activity. Meanwhile compound 13c showed the highest potentiation of phenobarbital induced sleep in mice. PMID:15646790

  15. A putative link between phagocytosis-induced apoptosis and hemocyanin-derived phenoloxidase activation.

    PubMed

    Coates, Christopher J; Whalley, Tim; Wyman, Michael; Nairn, Jacqueline

    2013-11-01

    Apoptosis and phagocytosis are crucial processes required for developmental morphogenesis, pathogen deterrence and immunomodulation in metazoans. We present data showing that amebocytes of the chelicerate, Limulus polyphemus, undergo phagocytosis-induced cell death after ingesting spores of the fungus, Beauveria bassiana, in vitro. The observed biochemical and morphological modifications associated with dying amebocytes are congruent with the hallmarks of apoptosis, including: extracellularisation of phosphatidylserine, intranucleosomal DNA fragmentation and an increase in caspase 3/7-like activities. Previous studies have demonstrated that phosphatidylserine is a putative endogenous activator of hemocyanin-derived phenoloxidase, inducing conformational changes that permit phenolic substrate access to the active site. Here, we observed extracellular hemocyanin-derived phenoloxidase activity levels increase in the presence of apoptotic amebocytes. Enzyme activity induced by phosphatidylserine or apoptotic amebocytes was reduced completely upon incubation with the phosphatidylserine binding protein, annexin V. We propose that phosphatidylserine redistributed to the outer plasma membrane of amebocytes undergoing phagocytosis-induced apoptosis could interact with hemocyanin, thus facilitating its conversion into a phenoloxidase-like enzyme, during immune challenge. PMID:23925540

  16. 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

  17. Antimalarial and Antileishmanial Activities of Histone Deacetylase Inhibitors with Triazole-Linked Cap Group

    PubMed Central

    Patil, Vishal; Guerrant, William; Chen, Po C.; Gryder, Berkley; Benicewicz, Derek B.; Khan, Shabana I.; Tekwani, Babu L.; Oyelere, Adegboyega K.

    2009-01-01

    Histone deacetylase inhibitors (HDACi) are endowed with plethora of biological functions including anti-proliferative, anti-inflammatory, anti-parasitic, and cognition-enhancing activities. Parsing the structure–activity relationship (SAR) for each disease condition is vital for long-term therapeutic applications of HDACi. We report in the present study specific cap group substitution patterns and spacer-group chain lengths that enhance the antimalarial and antileishmanial activity of aryltriazolylhydroxamates-based HDACi. We identified many compounds that are several folds selectively cytotoxic to the plasmodium parasites compared to standard HDACi. Also, a few of these compounds have antileishmanial activity that rivals that of miltefosine, the only currently available oral agent against visceral leishmaniasis. The anti-parasite properties of several of these compounds tracked well with their anti-HDAC activities. The results presented here provide further evidence on the suitability of HDAC inhibition as a viable therapeutic option to curb infections caused by apicomplexan protozoans and trypanosomatids. PMID:19914074

  18. A putative link between phagocytosis-induced apoptosis and hemocyanin-derived phenoloxidase activation.

    PubMed

    Coates, Christopher J; Whalley, Tim; Wyman, Michael; Nairn, Jacqueline

    2013-11-01

    Apoptosis and phagocytosis are crucial processes required for developmental morphogenesis, pathogen deterrence and immunomodulation in metazoans. We present data showing that amebocytes of the chelicerate, Limulus polyphemus, undergo phagocytosis-induced cell death after ingesting spores of the fungus, Beauveria bassiana, in vitro. The observed biochemical and morphological modifications associated with dying amebocytes are congruent with the hallmarks of apoptosis, including: extracellularisation of phosphatidylserine, intranucleosomal DNA fragmentation and an increase in caspase 3/7-like activities. Previous studies have demonstrated that phosphatidylserine is a putative endogenous activator of hemocyanin-derived phenoloxidase, inducing conformational changes that permit phenolic substrate access to the active site. Here, we observed extracellular hemocyanin-derived phenoloxidase activity levels increase in the presence of apoptotic amebocytes. Enzyme activity induced by phosphatidylserine or apoptotic amebocytes was reduced completely upon incubation with the phosphatidylserine binding protein, annexin V. We propose that phosphatidylserine redistributed to the outer plasma membrane of amebocytes undergoing phagocytosis-induced apoptosis could interact with hemocyanin, thus facilitating its conversion into a phenoloxidase-like enzyme, during immune challenge.

  19. Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity

    PubMed Central

    Ballaré, Cecilia; Lange, Martin; Lapinaite, Audrone; Martin, Gloria Mas; Morey, Lluis; Pascual, Gloria; Liefke, Robert; Simon, Bernd; Shi, Yang; Gozani, Or; Carlomagno, Teresa; Benitah, Salvador Aznar; Croce, Luciano Di

    2013-01-01

    Polycomb-group proteins are transcriptional repressors with essential roles in embryonic development. Polycomb repressive complex 2 (PRC2) contains the methyltransferase activity for Lys27. However, the role of other histone modifications in regulating PRC2 activity is just beginning to be understood. Here we show that direct recognition of methylated histone H3 Lys36 (H3K36me), a mark associated with activation, by the PRC2 subunit Phf19 is required for the full enzymatic activity of the PRC2 complex. Using NMR spectroscopy, we provide structural evidence for this interaction. Furthermore, we show that Phf19 binds to a subset of PRC2 targets in mouse embryonic stem cells and that this is required for their repression and for H3K27me3 deposition. These findings show that the interaction of Phf19 with H3K36me2 and H3K36me3 is essential for PRC2 complex activity and for proper regulation of gene repression in embryonic stem cells. PMID:23104054

  20. 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.

  1. 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

  2. Generation of nitric oxide from nitrite by carbonic anhydrase: a possible link between metabolic activity and vasodilation.

    PubMed

    Aamand, Rasmus; Dalsgaard, Thomas; Jensen, Frank B; Simonsen, Ulf; Roepstorff, Andreas; Fago, Angela

    2009-12-01

    In catalyzing the reversible hydration of CO2 to bicarbonate and protons, the ubiquitous enzyme carbonic anhydrase (CA) plays a crucial role in CO2 transport, in acid-base balance, and in linking local acidosis to O2 unloading from hemoglobin. Considering the structural similarity between bicarbonate and nitrite, we hypothesized that CA uses nitrite as a substrate to produce the potent vasodilator nitric oxide (NO) to increase local blood flow to metabolically active tissues. Here we show that CA readily reacts with nitrite to generate NO, particularly at low pH, and that the NO produced in the reaction induces vasodilation in aortic rings. This reaction occurs under normoxic and hypoxic conditions and in various tissues at physiological levels of CA and nitrite. Furthermore, two specific inhibitors of the CO2 hydration, dorzolamide and acetazolamide, increase the CA-catalyzed production of vasoactive NO from nitrite. This enhancing effect may explain the known vasodilating effects of these drugs and indicates that CO2 and nitrite bind differently to the enzyme active site. Kinetic analyses show a higher reaction rate at high pH, suggesting that anionic nitrite participates more effectively in catalysis. Taken together, our results reveal a novel nitrous anhydrase enzymatic activity of CA that would function to link the in vivo main end products of energy metabolism (CO2/H+) to the generation of vasoactive NO. The CA-mediated NO production may be important to the correlation between blood flow and metabolic activity in tissues, as occurring for instance in active areas of the brain. PMID:19820197

  3. Hyperglycemia induces memory impairment linked to increased acetylcholinesterase activity in zebrafish (Danio rerio).

    PubMed

    Capiotti, Katiucia Marques; De Moraes, Daiani Almeida; Menezes, Fabiano Peres; Kist, Luiza Wilges; Bogo, Maurício Reis; Da Silva, Rosane Souza

    2014-11-01

    Diabetes mellitus, which causes hyperglycemia, affects the central nervous system and can impairs cognitive functions, such as memory. The aim of this study was to investigate the effects of hyperglycemia on memory as well as on the activity of acethylcholinesterase. Hyperglycemia was induced in adult zebrafish by immersion in glucose 111mM by 14 days. The animals were divided in 4 groups: control, glucose-treated, glucose-washout 7-days and glucose-washout 14-days. We evaluated the performance in inhibitory avoidance task and locomotor activity. We also determined acethylcholinesterase activity and gene expression from whole brain. In order to counteract the effect of hyperglycemia underlined by effects on acethylcholinesterase activity, we treated the animals with galantamine (0.05ng/g), an inhibitor of this enzyme. Also we evaluated the gene expression of insulin receptor and glucose transporter from zebrafish brain. The hyperglycemia promoted memory deficit in adult zebrafish, which can be explained by increased AChE activity. The ache mRNA levels from zebrafish brain were decrease in 111mM glucose group and returned to normal levels after 7 days of glucose withdrawal. Insulin receptors (insra-1, insra-2, insrb-1 and insrb-2) and glut-3 mRNA levels were not significantly changed. Our results also demonstrated that galantamine was able to reverse the memory deficit caused by hyperglycemia, demonstrating that these effects involve modulation of AChE activity. These data suggest that the memory impairment induced by hyperglycemia is underlined by the cholinergic dysfunction caused by the mechanisms involving the control of acetylcholinesterase function and gene expression. PMID:25157430

  4. Enzymatically Regulated Peptide Pairing and Catalysis for the Bioanalysis of Extracellular Prometastatic Activities of Functionally Linked Enzymes.

    PubMed

    Li, Hao; Huang, Yue; Yu, Yue; Li, Tianqi; Li, Genxi; Anzai, Jun-Ichi

    2016-05-03

    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.

  5. 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

  6. Adolescents' Occupational and Educational Aspirations and Expectations: Links to High School Activities and Adult Educational Attainment

    ERIC Educational Resources Information Center

    Beal, Sarah J.; Crockett, Lisa J.

    2010-01-01

    This longitudinal study explored adolescents' future-oriented cognitions, current activities, and later educational attainment using data from 317 adolescents (55% female; mean age = 14.98 years, SD = 0.85) followed into early adulthood. Aspirations and expectations regarding work and education showed modest stability from year to year.…

  7. 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. PMID:1786224

  8. Centrally patterned rhythmic activity integrated by a peripheral circuit linking multiple oscillators.

    PubMed

    Jellies, John; Kueh, Daniel

    2012-08-01

    The central pattern generator for heartbeat in the medicinal leech, Hirudo generates rhythmic activity conveyed by heart excitor motor neurons in segments 3-18 to coordinate the bilateral tubular hearts and side vessels. We focus on behavior and the influence of previously un-described peripheral nerve circuitry. Extracellular recordings from the valve junction (VJ) where afferent vessels join the heart tube were combined with optical recording of contractions. Action potential bursts at VJs occurred in advance of heart tube and afferent vessel contractions. Transections of nerves were performed to reduce the output of the central pattern generator reaching the heart tube. Muscle contractions persisted but with a less regular rhythm despite normal central pattern generator rhythmicity. With no connections between the central pattern generator and heart tube, a much slower rhythm became manifest. Heart excitor neuron recordings showed that peripheral activity might contribute to the disruption of centrally entrained contractions. In the model presented, peripheral activity would normally modify the activity actually reaching the muscle. We also propose that the fundamental efferent unit is not a single heart excitor neuron, but rather is a functionally defined unit of about three adjacent motor neurons and the peripheral assembly of coupled peripheral oscillators.

  9. Linking New Learning with Previous Experiences: An Activity in Teaching Dimensional Analysis.

    ERIC Educational Resources Information Center

    Schmidt, Stan M.; Werner, Jana Rae

    Throughout America's secondary science classrooms, students struggle to master fundamental science principles, especially when math-related applications are involved. For example, in chemistry students struggle to solve quantitative problems. This paper presents an activity that leads to a useful understanding of dimensional analysis; i.e., unit…

  10. Enzyme activity and structural dynamics linked to micelle formation: a fluorescence anisotropy and ESR study.

    PubMed

    Chin, Michael; Somasundaran, Ponisseril

    2014-01-01

    Activities of the enzymes, protease subtilisin and horse radish peroxidase (HRP) have been increased 50 and 40%, respectively, in the presence of the nonionic surfactant, alkyl polyglucoside, compared with the activities in buffer alone. This enzyme hyperactivity reaches a peak at 3.0 mm of surfactant. Investigation into the structure of surfactant aggregates indicates "giant" micelle superstructures at this range of surfactant concentration of 1.7 μm in diameter--dramatically decreasing to 60 and 70 nm at higher surfactant concentrations, while surface tension measurements indicate two critical micelle concentration inflection points at 0.2 and 5.0 mm, which suggests transitions in micelle structure with respect to concentration. Furthermore, electron spin resonance (ESR) indicates that the micelles in first critical micelle concentration regime are loosely packed relative to the second aggregate phase. We hypothesize that this loose packing results in diminished hydration shell repulsion between the micelles, leading to the large, micrometer-sized aggregates. We further hypothesize that it is the interaction with these loosely packed micelles that affects the flexibility of the HRP and protease enzyme structure. Time-resolved fluorescence anisotropy of subtilisin in Brij-30 indicates increasing flexibility of catalytic active site with surfactant concentration. This is correlated with an increase in enzymatic activity. PMID:24303849

  11. 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…

  12. 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

  13. Accumulation of wildtype and ALS-linked mutated VAPB impairs activity of the proteasome.

    PubMed

    Moumen, Anice; Virard, Isabelle; Raoul, Cédric

    2011-01-01

    Cellular homeostasis relies on a tight control of protein synthesis, folding and degradation, in which the endoplasmic reticulum (ER) quality control and the ubiquitin proteasome system (UPS) have an instrumental function. ER stress and aberrant accumulation of misfolded proteins represent a pathological signature of amyotrophic lateral sclerosis (ALS), a fatal paralytic disorder caused by the selective degeneration of motoneurons in the brain and spinal cord. Mutations in the ER-resident protein VAPB have been associated with familial forms of the disease. ALS-linked mutations cause VAPB to form cytoplasmic aggregates. We previously demonstrated that viral-mediated expression of both wildtype and mutant human VAPB (hVAPB) leads to an ER stress response that contributes to the selective death of motoneurons. However, the mechanisms behind ER stress, defective UPS and hVAPB-associated motoneuron degeneration remain elusive. Here, we show that the overexpression of wildtype and mutated hVAPB, which is found to be less stable than the wildtype protein, leads to the abnormal accumulation of ubiquitin and ubiquitin-like protein conjugates in non-human primate cells. We observed that overexpression of both forms of hVAPB elicited an ER stress response. Treatment of wildtype and mutated hVAPB expressing cells with the ER stress inhibitor salubrinal diminished the burden of ubiquitinated proteins, suggesting that ER stress contributes to the impairment of proteasome function. We also found that both wildtype and mutated hVAPB can associate with the 20S proteasome, which was found to accumulate at the ER with wildtype hVAPB or in mutant hVAPB aggregates. Our results suggest that ER stress and corruption of the proteasome function might contribute to the aberrant protein homeostasis associated with hVAPB.

  14. Physical Activity and Health Perception in Aging: Do Body Mass and Satisfaction Matter? A Three-Path Mediated Link.

    PubMed

    Condello, Giancarlo; 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

  15. 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

  16. Physical Activity and Health Perception in Aging: Do Body Mass and Satisfaction Matter? A Three-Path Mediated Link.

    PubMed

    Condello, Giancarlo; 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

  17. 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. PMID:24959998

  18. 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. PMID:26593574

  19. Prefrontal cortex activity during motor tasks with additional mental load requiring attentional demand: a near-infrared spectroscopy study.

    PubMed

    Mandrick, Kevin; Derosiere, Gérard; Dray, Gérard; Coulon, Denis; Micallef, Jean-Paul; Perrey, Stéphane

    2013-07-01

    Functional near-infrared spectroscopy (fNIRS) is suitable for investigating cerebral oxygenation changes during motor and/or mental tasks. In the present study, we investigated how an additional mental load during a motor task at two submaximal loadings affects the fNIRS-measured brain activation over the right prefrontal cortex (PFC). Fifteen healthy males performed isometric grasping contractions at 15% and 30% of the maximal voluntary contraction (MVC) with or without an additional mental (i.e., arithmetic) task. Mental performance, force variability, fNIRS and subjective perception responses were measured in each condition. The performance of the mental task decreased significantly while the force variability increased significantly at 30% MVC as compared to 15% MVC, suggesting that performance of dual-task required more attentional resources. PFC activity increased significantly as the effort increased from 15% to 30% MVC (p<.001). Although a larger change in the deoxyhemoglobin was observed in dual-task conditions (p=.051), PFC activity did not change significantly as compared to the motor tasks alone. In summary, participants were unable to invest more attention and effort in performing the more difficult levels in order to maintain adequate mental performance.

  20. Prefrontal cortex activity during motor tasks with additional mental load requiring attentional demand: a near-infrared spectroscopy study.

    PubMed

    Mandrick, Kevin; Derosiere, Gérard; Dray, Gérard; Coulon, Denis; Micallef, Jean-Paul; Perrey, Stéphane

    2013-07-01

    Functional near-infrared spectroscopy (fNIRS) is suitable for investigating cerebral oxygenation changes during motor and/or mental tasks. In the present study, we investigated how an additional mental load during a motor task at two submaximal loadings affects the fNIRS-measured brain activation over the right prefrontal cortex (PFC). Fifteen healthy males performed isometric grasping contractions at 15% and 30% of the maximal voluntary contraction (MVC) with or without an additional mental (i.e., arithmetic) task. Mental performance, force variability, fNIRS and subjective perception responses were measured in each condition. The performance of the mental task decreased significantly while the force variability increased significantly at 30% MVC as compared to 15% MVC, suggesting that performance of dual-task required more attentional resources. PFC activity increased significantly as the effort increased from 15% to 30% MVC (p<.001). Although a larger change in the deoxyhemoglobin was observed in dual-task conditions (p=.051), PFC activity did not change significantly as compared to the motor tasks alone. In summary, participants were unable to invest more attention and effort in performing the more difficult levels in order to maintain adequate mental performance. PMID:23665138

  1. Effectiveness of Taste Lessons with and without additional experiential learning activities on children's psychosocial determinants of vegetables consumption.

    PubMed

    Battjes-Fries, Marieke C E; Haveman-Nies, Annemien; van Dongen, Ellen J I; Meester, Hante J; van den Top-Pullen, Rinelle; de Graaf, Kees; van 't Veer, Pieter

    2016-10-01

    Experiential learning methods seem to be promising to enhance healthy eating behaviour in children. Therefore, this study compared the effectiveness of the Dutch programme Taste Lessons with and without additional experiential learning activities on children's psychosocial determinants of vegetable consumption. In a quasi-experimental design, 800 children aged 8-11 years old from 34 elementary schools participated in a Taste Lessons (TL: 5 lessons) group, a Taste Lessons Vegetable Menu (TLVM: TL with 3 added experiential learning activities) group, and a control group. During a baseline and follow-up measurement, children completed a questionnaire on psychosocial determinants towards vegetables consumption. Multilevel regression analyses were conducted to compare changes in the determinants between the TLVM group and the TL group, and between the two intervention groups and the control group. The TLVM group showed a significantly higher increase in knowledge (p < 0.001), attitude and subjective norm of the teacher (both p < 0.05), whereas the TL group only showed a significantly higher increase in knowledge (p < 0.001) compared to the control group. Increases in knowledge (p < 0.10), subjective norm (p < 0.10) and cooking self-efficacy (p < 0.05) were higher in the TLVM group than in the TL group. Therefore, more and stronger effects were found in children who participated in the additional hands-on activities. PMID:27317617

  2. 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.

  3. A Stable Bacterial Peroxidase with Novel Halogenating Activity and an Autocatalytically Linked Heme Prosthetic Group*

    PubMed Central

    Auer, Markus; Gruber, Clemens; Bellei, Marzia; Pirker, Katharina F.; Zamocky, Marcel; Kroiss, Daniela; Teufer, Stefan A.; Hofbauer, Stefan; Soudi, Monika; Battistuzzi, Gianantonio; Furtmüller, Paul G.; Obinger, Christian

    2013-01-01

    Reconstructing the phylogenetic relationships of the main evolutionary lines of the mammalian peroxidases lactoperoxidase and myeloperoxidase revealed the presence of novel bacterial heme peroxidase subfamilies. Here, for the first time, an ancestral bacterial heme peroxidase is shown to possess a very high bromide oxidation activity (besides conventional peroxidase activity). The recombinant protein allowed monitoring of the autocatalytic peroxide-driven formation of covalent heme to protein bonds. Thereby, the high spin ferric rhombic heme spectrum became similar to lactoperoxidase, the standard reduction potential of the Fe(III)/Fe(II) couple shifted to more positive values (−145 ± 10 mV at pH 7), and the conformational and thermal stability of the protein increased significantly. We discuss structure-function relationships of this new peroxidase in relation to its mammalian counterparts and ask for its putative physiological role. PMID:23918925

  4. 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.

  5. The activation of mechanisms linking judgements of work design and management with musculoskeletal pain.

    PubMed

    Randall, Raymond; Griffiths, Amanda; Cox, Tom; Welsh, Claire

    2002-01-15

    The report of work-related musculoskeletal pain may be related to worker evaluations of the design and management of work through two mechanisms: one biomechanical and the other stress-related. This study of engineering workers (n = 204) explored the validity of these mechanisms using sequential logistic regression. Analyses suggested that workers' ratings of the adequacy of the design and management of their work were related to their report of work-related musculoskeletal pain. However, the mechanisms appeared to be activated in certain conditions. The reporting of pain in the upper body was both biomechanically- and stress-related, whereas that in the lower body was only biomechanically-related. It is argued that the mechanism activated appeared to be determined by the anatomical location of the pain, and probably the variance shared between the different aspects of work design and management, on the one hand, and the mechanical load of the job, on the other. PMID:11964192

  6. 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. PMID:26846538

  7. Bassoon and piccolo regulate ubiquitination and link presynaptic molecular dynamics with activity-regulated gene expression.

    PubMed

    Ivanova, Daniela; Dirks, Anika; Fejtova, Anna

    2016-10-01

    Release of neurotransmitter is executed by complex multiprotein machinery, which is assembled around the presynaptic cytomatrix at the active zone. One well-established function of this proteinaceous scaffold is the spatial organization of synaptic vesicle cluster, the protein complexes that execute membrane fusion and compensatory endocytosis, and the transmembrane molecules important for alignment of pre- and postsynaptic structures. The presynaptic cytomatrix proteins function also in processes other than the formation of a static frame for assembly of the release apparatus and synaptic vesicle cycling. They actively contribute to the regulation of multiple steps in this process and are themselves an important subject of regulation during neuronal plasticity. We are only beginning to understand the mechanisms and signalling pathways controlling these regulations. They are mainly dependent on posttranslational modifications, including phosphorylation and small-molecules conjugation, such as ubiquitination. Ubiquitination of presynaptic proteins might lead to their degradation by proteasomes, but evidence is growing that this modification also affects their function independently of their degradation. Signalling from presynapse to nucleus, which works on a much slower time scale and more globally, emerged as an important mechanism for persistent usage-dependent and homeostatic neuronal plasticity. Recently, two new functions for the largest presynaptic scaffolding proteins bassoon and piccolo emerged. They were implied (1) in the regulation of specific protein ubiquitination and proteasome-mediated proteolysis that potentially contributes to short-term plasticity at the presynapse and (2) in the coupling of activity-induced molecular rearrangements at the presynapse with reprogramming of expression of neuronal activity-regulated genes.

  8. Linking algal growth inhibition to chemical activity: baseline toxicity required 1% of saturation.

    PubMed

    Schmidt, Stine N; Mayer, Philipp

    2015-02-01

    Recently, high-quality data were published on the algal growth inhibition caused by 50 non-polar narcotic compounds, of which 39 were liquid compounds with defined water solubility. In the present study, the toxicity data for these liquids were applied to challenge the chemical activity range for baseline toxicity. First, the reported effective concentrations (EC50) were divided by the respective water solubilities (S water), since the obtained EC50/S water ratio essentially equals the effective chemical activity (Ea50). The majority of EC50/S water ratios were within the expected chemical activity range of 0.01-0.1 for baseline toxicity, and none of the ratios were significantly below 0.01. On a practical level, these findings suggest EC50 values for baseline toxicity to be at or above 1% of liquid solubility, which would have been accurate or conservative for all 39 liquids with defined water solubility in the applied dataset. On an environmental risk assessment level, predicted no-effect concentrations (PNECs) for baseline toxicity could even be set as a percentage of saturation, which can easily be extended to mixtures. However, EC50 values well below 1% of liquid saturation can still occur and would be a direct indication of excess toxicity.

  9. Active hypothalamic-pituitary-gonadal axis in an infant with X-linked adrenal hypoplasia congenita.

    PubMed

    Takahashi, T; Shoji, Y; Shoji, Y; Haraguchi, N; Takahashi, I; Takada, G

    1997-03-01

    To evaluate the hypothalamic-pituitary-gonadal axis in an infant with adrenal hypoplasia congenita, we measured the serum levels of testosterone and performed a luteinizing hormone-releasing hormone stimulation test. The diagnosis was made because of the presence of a mutation, A300V, in the DAX-1 gene. The results demonstrated an active hypothalamic-pituitary-gonadal axis, with adult-level testosterone of 266 ng/dl on day 0, and maintenance of testosterone concentration in the 100 to 250 ng/dl range for 140 days as expected. The luteinizing hormone-releasing hormone lest was compatible with an active pituitary gland with a luteinizing hormone peak of 13.1 IU/L and a follicle-stimulating hormone of 5.0 IU/L We conclude that the DAX-1 mutation does allow a normal reproductive axis at birth. We speculate that sometime between infancy and puberty this mutation in the DAX-1 gene leads to an inability to activate the reproductive axis from its childhood suppression; thus puberty will not develop in this infant.

  10. Activation of GCN2 kinase by ribosome stalling links translation elongation with translation initiation

    PubMed Central

    Ishimura, Ryuta; Nagy, Gabor; Dotu, Ivan; Chuang, Jeffrey H; Ackerman, Susan L

    2016-01-01

    Ribosome stalling during translation has recently been shown to cause neurodegeneration, yet the signaling pathways triggered by stalled elongation complexes are unknown. To investigate these pathways we analyzed the brain of C57BL/6J-Gtpbp2nmf205-/- mice in which neuronal elongation complexes are stalled at AGA codons due to deficiencies in a tRNAArgUCU tRNA and GTPBP2, a mammalian ribosome rescue factor. Increased levels of phosphorylation of eIF2α (Ser51) were detected prior to neurodegeneration in these mice and transcriptome analysis demonstrated activation of ATF4, a key transcription factor in the integrated stress response (ISR) pathway. Genetic experiments showed that this pathway was activated by the eIF2α kinase, GCN2, in an apparent deacylated tRNA-independent fashion. Further we found that the ISR attenuates neurodegeneration in C57BL/6J-Gtpbp2nmf205-/- mice, underscoring the importance of cellular and stress context on the outcome of activation of this pathway. These results demonstrate the critical interplay between translation elongation and initiation in regulating neuron survival during cellular stress. DOI: http://dx.doi.org/10.7554/eLife.14295.001 PMID:27085088

  11. Intersubject variability in fearful face processing: the link between behavior and neural activation.

    PubMed

    Doty, Tracy J; Japee, Shruti; Ingvar, Martin; Ungerleider, Leslie G

    2014-12-01

    Stimuli that signal threat show considerable variability in the extents 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 versus neutral face categorization, we uncovered a network of areas underlying variability in threat processing in healthy adults. We explicitly altered expectations by presenting face images at three different expectation levels: 80 %, 50 %, and 20 %. Subjects were instructed to report as quickly and accurately as possible whether the face was fearful (signaled threat) or not. An uninformative cue preceded each face by 4 s. By taking the difference between reaction times (RTs) to fearful and neutral faces, we quantified an overall fear RT bias (i.e., faster to fearful than to 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.

  12. Quantitative imaging of transcription in living Drosophila embryos links polymerase activity to patterning.

    PubMed

    Garcia, Hernan G; Tikhonov, Mikhail; Lin, Albert; Gregor, Thomas

    2013-11-01

    Spatiotemporal patterns of gene expression are fundamental to every developmental program. The resulting macroscopic domains have been mainly characterized by their levels of gene products. However, the establishment of such patterns results from differences in the dynamics of microscopic events in individual cells such as transcription. It is unclear how these microscopic decisions lead to macroscopic patterns, as measurements in fixed tissue cannot access the underlying transcriptional dynamics. In vivo transcriptional dynamics have long been approached in single-celled organisms, but never in a multicellular developmental context. Here, we directly address how boundaries of gene expression emerge in the Drosophila embryo by measuring the absolute number of actively transcribing polymerases in real time in individual nuclei. Specifically, we show that the formation of a boundary cannot be quantitatively explained by the rate of mRNA production in each cell, but instead requires amplification of the dynamic range of the expression boundary. This amplification is accomplished by nuclei randomly adopting active or inactive states of transcription, leading to a collective effect where the fraction of active nuclei is modulated in space. Thus, developmental patterns are not just the consequence of reproducible transcriptional dynamics in individual nuclei, but are the result of averaging expression over space and time.

  13. Examining the link between framed physical activity ads and behavior among women.

    PubMed

    Berenbaum, Erin; Latimer-Cheung, Amy E

    2014-06-01

    Gain-framed messages are more effective at promoting physical activity than loss-framed messages. However, the mechanism through which this effect occurs is unclear. The current experiment examined the effects of message framing on variables described in the communication behavior change model (McGuire, 1989), as well as the mediating effects of these variables on the message-frame-behavior relationship. Sixty low-to-moderately active women viewed 20 gain- or loss-framed ads and five control ads while their eye movements were recorded via eye tracking. The gain-framed ads attracted greater attention, ps < .05; produced more positive attitudes, p = .06; were better recalled, p < .001; influenced decisions to be active, p = .07; and had an immediate and delayed impact on behavior, ps < .05, compared with the loss-framed messages. Mediation analyses failed to reveal any significant effects. This study demonstrates the effects of framed messages on several outcomes; however, the mechanisms underlying these effects remain unclear.

  14. 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.

  15. 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. PMID:24161719

  16. Activation of GCN2 kinase by ribosome stalling links translation elongation with translation initiation.

    PubMed

    Ishimura, Ryuta; Nagy, Gabor; Dotu, Ivan; Chuang, Jeffrey H; Ackerman, Susan L

    2016-01-01

    Ribosome stalling during translation has recently been shown to cause neurodegeneration, yet the signaling pathways triggered by stalled elongation complexes are unknown. To investigate these pathways we analyzed the brain of C57BL/6J-Gtpbp2(nmf205)(-/-) mice in which neuronal elongation complexes are stalled at AGA codons due to deficiencies in a tRNA(Arg)UCU tRNA and GTPBP2, a mammalian ribosome rescue factor. Increased levels of phosphorylation of eIF2α (Ser51) were detected prior to neurodegeneration in these mice and transcriptome analysis demonstrated activation of ATF4, a key transcription factor in the integrated stress response (ISR) pathway. Genetic experiments showed that this pathway was activated by the eIF2α kinase, GCN2, in an apparent deacylated tRNA-independent fashion. Further we found that the ISR attenuates neurodegeneration in C57BL/6J-Gtpbp2(nmf205)(-/-) mice, underscoring the importance of cellular and stress context on the outcome of activation of this pathway. These results demonstrate the critical interplay between translation elongation and initiation in regulating neuron survival during cellular stress. PMID:27085088

  17. 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

  18. 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.

  19. Linking wheelchair kinetics to glenohumeral joint demand during everyday accessibility activities.

    PubMed

    Holloway, Catherine S; Symonds, Andrew; Suzuki, Tatsuto; Gall, Angela; Smitham, Peter; Taylor, Stephen

    2015-01-01

    The aim of the study was to investigate if push-rim kinetics could be used as markers of glenohumeral joint demand during manual wheelchair accessibility activities; demonstrating a method of biomechanical analysis that could be used away from the laboratory. Propulsion forces, trunk and upper limb kinematics and surface electromyography were recorded during four propulsion tasks (level, 2.5% cross slope, 6.5% incline and 12% incline). Kinetic and kinematic data were applied to an OpenSim musculoskeletal model of the trunk and upper limb, to enable calculation of glenohumeral joint contact force. Results demonstrated a positive correlation between propulsion forces and glenohumeral joint contact forces. Both propulsion forces and joint contact forces increased as the task became more challenging. Participants demonstrated increases in trunk flexion angle as the requirement for force application increased, significantly so in the 12% incline. There were significant increases in both resultant glenohumeral joint contact forces and peak and mean normalized muscle activity levels during the incline tasks. This study demonstrated the high demand placed on the glenohumeral joint during accessibility tasks, especially as the gradient of incline increases. A lightweight instrumented wheelchair wheel has potential to guide the user to minimize upper limb demand during daily activity.

  20. Intersubject variability in fearful face processing: the link between behavior and neural activation.

    PubMed

    Doty, Tracy J; Japee, Shruti; Ingvar, Martin; Ungerleider, Leslie G

    2014-12-01

    Stimuli that signal threat show considerable variability in the extents 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 versus neutral face categorization, we uncovered a network of areas underlying variability in threat processing in healthy adults. We explicitly altered expectations by presenting face images at three different expectation levels: 80 %, 50 %, and 20 %. Subjects were instructed to report as quickly and accurately as possible whether the face was fearful (signaled threat) or not. An uninformative cue preceded each face by 4 s. By taking the difference between reaction times (RTs) to fearful and neutral faces, we quantified an overall fear RT bias (i.e., faster to fearful than to 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

  1. Formation of gold nanostructures on copier paper surface for cost effective SERS active substrate - Effect of halide additives

    NASA Astrophysics Data System (ADS)

    Desmonda, Christa; Kar, Sudeshna; Tai, Yian

    2016-03-01

    In this study, we report the simple fabrication of an active substrate assisted by gold nanostructures (AuNS) for application in surface-enhanced Raman scattering (SERS) using copier paper, which is a biodegradable and cost-effective material. As cellulose is the main component of paper, it can behave as a reducing agent and as a capping molecule for the synthesis of AuNS on the paper substrate. AuNS can be directly generated on the surface of the copier paper by addition of halides. The AuNS thus synthesized were characterized by ultraviolet-visible spectroscopy, SEM, XRD, and XPS. In addition, the SERS effect of the AuNS-paper substrates synthesized by using various halides was investigated by using rhodamine 6G and melamine as probe molecules.

  2. 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. PMID:25801795

  3. 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.

  4. Exercise can induce temporary mitochondrial and contractile dysfunction linked to impaired respiratory chain complex activity.

    PubMed

    Schoepe, Maria; Schrepper, Andrea; Schwarzer, Michael; Osterholt, Moritz; Doenst, Torsten

    2012-01-01

    Exercise is considered to elicit a physiological response of the heart. Previous studies investigated the influence of repetitive exercise only at the end of the training period. We assessed the impact of 2 exercise protocols, differing in their treadmill inclination, on cardiac and mitochondrial function at different times during the training period. Within 10 weeks, animals trained with 16% incline developed hypertrophy (left ventricular posterior wall thickness: 1.6 ± 0.1 vs 2.4 ± 0.1 mm; P < .05) with normal function (ejection fraction: 75.2% ± 2.5% vs 75.6% ± 2.1%). However, at 6 weeks, there was temporary impairment of contractile function (ejection fraction: 74.5% ± 1.67% vs 65.8% ± 2.3%; P < .05) associated with decreased mitochondrial respiratory capacity (state 3 respiration: 326 ± 71 vs 161 ± 22 natoms/[min mg protein]; P < .05) and a gene expression shift from the adult (α) to the fetal (β) myosin heavy chain isoform. Although peroxisome proliferator-activated receptor gamma coactivator-1α expression was normal, nuclear respiratory factors (NRFs)-1 and -2 were significantly reduced (NRF-1: 1.00 ± 0.16 vs 0.55 ± 0.09; NRF-2: 1.00 ± 0.11 vs 0.63 ± 0.07; P < .05) after 6 weeks. These findings were associated with a reduction of electron transport chain complexes I and IV activity (complex I: 1016 ± 67 vs 758 ± 71 nmol/[min mg protein]; complex IV: 18768 ± 1394 vs 14692 ± 960 nmol/[min mg protein]; P < .05). Messenger RNA expression of selected nuclear encoded subunits of the electron transport chain was unchanged at all investigated time points. In contrast, animals trained with 10% incline showed less hypertrophy and normal function in echocardiography, normal maximal respiratory capacity, and unchanged complex activities at all 3 time points. Repetitive exercise may cause contractile and mitochondrial dysfunction characterized by impaired respiratory chain complex activities. This activity reduction is temporary and intensity related.

  5. 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

  6. Whence flavins? Redox-active ribonucleotides link metabolism and genome repair to the RNA world.

    PubMed

    Nguyen, Khiem Van; Burrows, Cynthia J

    2012-12-18

    Present-day organisms are under constant environmental stress that damages bases in DNA, leading to mutations. Without DNA repair processes to correct these errors, such damage would be catastrophic. Organisms in all kingdoms have repair processes ranging from direct reversal to base excision and nucleotide excision repair, and the recently characterized giant viruses also include these mechanisms. At what point in the evolution of genomes did active repair mechanisms become critical? In particular, how did early RNA genomes protect themselves from UV photodamage that would have hampered nonenzymatic replication and led to a mutation rate too high to pass on accurate sequence information from one generation to the next? Photolyase is a widespread and phylogenetically ancient enzyme that utilizes longer wavelength light to cleave thymine dimers in DNA produced via photodamage. The protein serves as a binding scaffold but does not contribute to the catalytic chemistry; the action of the dinucleotide cofactor FADH(2) breaks the chemical bonds. This small bit of RNA, hailed as a "fossil of the RNA World," contains the flavin heterocycle, whose redox activity has been harnessed for myriad functions of life from metabolism to DNA repair. In present-day biochemistry, flavin biosynthesis begins with guanosine and proceeds through seven steps catalyzed by protein-based enzymes. This leads to the question of how flavins originally evolved. Did the RNA world include ancestral RNA bases with greater redox activity than G, A, C, and U that were capable of photorepair of uracil dimers? Could those ancestral bases have chemically evolved to the current flavin structure? Or did flavins already exist from prebiotic chemical synthesis? And were they then co-opted as catalysts for repair sometime after metabolism was established? In this Account, we analyze simple derivatives of guanosine and other bases that show two prerequisites for flavin-like photolyase activity: a significantly

  7. Accurate Detection of Adenylation Domain Functions in Nonribosomal Peptide Synthetases by an Enzyme-linked Immunosorbent Assay System Using Active Site-directed Probes for Adenylation Domains.

    PubMed

    Ishikawa, Fumihiro; Miyamoto, Kengo; Konno, Sho; Kasai, Shota; Kakeya, Hideaki

    2015-12-18

    A significant gap exists between protein engineering and enzymes used for the biosynthesis of natural products, largely because there is a paucity of strategies that rapidly detect active-site phenotypes of the enzymes with desired activities. Herein, we describe a proof-of-concept study of an enzyme-linked immunosorbent assay (ELISA) system for the adenylation (A) domains in nonribosomal peptide synthetases (NRPSs) using a combination of active site-directed probes coupled to a 5'-O-N-(aminoacyl)sulfamoyladenosine scaffold with a biotin functionality that immobilizes probe molecules onto a streptavidin-coated solid support. The recombinant NRPSs have a C-terminal His-tag motif that is targeted by an anti-6×His mouse antibody as the primary antibody and a horseradish peroxidase-linked goat antimouse antibody as the secondary antibody. These probes can selectively capture the cognate A domains by ligand-directed targeting. In addition, the ELISA technique detected A domains in the crude cell-free homogenates from the Escherichia coli expression systems. When coupled with a chromogenic substrate, the antibody-based ELISA technique can visualize probe-protein binding interactions, which provides accurate readouts of the A-domain functions in NRPS enzymes. To assess the ELISA-based engineering of the A domains of NRPSs, we reprogramed 2,3-dihydroxybenzoic acid (DHB)-activating enzyme EntE toward salicylic acid (Sal)-activating enzymes and investigated a correlation between binding properties for probe molecules and enzyme catalysts. We generated a mutant of EntE that displayed negligible loss in the kcat/Km value with the noncognate substrate Sal and a corresponding 48-fold decrease in the kcat/Km value with the cognate substrate DHB. The resulting 26-fold switch in substrate specificity was achieved by the replacement of a Ser residue in the active site of EntE with a Cys toward the nonribosomal codes of Sal-activating enzymes. Bringing a laboratory ELISA technique

  8. Cognitive Impairment in Humanized APPxPS1 Mice is Linked to Aβ1-42 and NOX Activation

    PubMed Central

    Bruce-Keller, Annadora J.; Gupta, Sunita; Knight, Alecia G.; Beckett, Tina L.; McMullen, Jessica M.; Davis, Paulina R.; Murphy, M. Paul; Van Eldik, Linda J.; Clair, Daret St; Keller, Jeffrey N.

    2011-01-01

    Cognitive impairment in Alzheimer’s disease (AD) is strongly associated with both extensive deposition of amyloid β peptides and oxidative stress, but the exact role of these indices in the development of dementia is not clear. This study was designed to determine the relationship between cognitive impairment, activation of the free radical producing enzyme NADPH oxidase (NOX), and progressive changes in Aβ deposition and solubility in humanized APP × PS1 knock-in mice of increasing age. Data show that cognitive performance and expression of key synaptic proteins was progressively decreased in aging APP × PS1 mice. Likewise, NOX activity and expression of the specific NOX subunit NOX4 was significantly increased in APP × PS1 mice in an age-dependent manner, and NOX activity and cognitive impairment shared a significant linear relationship. Data further show that age-dependent increases in Aβ1-42 had a significant linear relationship with both NOX activity and cognitive performance in APP × PS1 knock-in mice. Collectively, these data show that NOX expression and activity are significantly upregulated with age in this humanized model of Aβ pathogenesis, and suggest that NOX-associated redox pathways are intimately linked to both the loss of cognitive function and the deposition of Aβ1-42. PMID:21798347

  9. SHP2-interacting Transmembrane Adaptor Protein (SIT), A Novel Disulfide-linked Dimer Regulating Human T Cell Activation

    PubMed Central

    Marie-Cardine, Anne; Kirchgessner, Henning; Bruyns, Eddy; Shevchenko, Andrej; Mann, Matthias; Autschbach, Frank; Ratnofsky, Sheldon; Meuer, Stefan; Schraven, Burkhart

    1999-01-01

    T lymphocytes express several low molecular weight transmembrane adaptor proteins that recruit src homology (SH)2 domain–containing intracellular molecules to the cell membrane via tyrosine-based signaling motifs. We describe here a novel molecule of this group termed SIT (SHP2 interacting transmembrane adaptor protein). SIT is a disulfide-linked homodimeric glycoprotein that is expressed in lymphocytes. After tyrosine phosphorylation by src and possibly syk protein tyrosine kinases SIT recruits the SH2 domain–containing tyrosine phosphatase SHP2 via an immunoreceptor tyrosine-based inhibition motif. Overexpression of SIT in Jurkat cells downmodulates T cell receptor– and phytohemagglutinin-mediated activation of the nuclear factor of activated T cells (NF-AT) by interfering with signaling processes that are probably located upstream of activation of phospholipase C. However, binding of SHP2 to SIT is not required for inhibition of NF-AT induction, suggesting that SIT not only regulates NF-AT activity but also controls NF-AT unrelated pathways of T cell activation involving SHP2. PMID:10209036

  10. Comparison of biological activities of human antithrombins with high-mannose or complex-type nonfucosylated N-linked oligosaccharides.

    PubMed

    Yamada, Tsuyoshi; Kanda, Yutaka; Takayama, Makoto; Hashimoto, Akitoshi; Sugihara, Tsutomu; Satoh-Kubota, Ai; Suzuki-Takanami, Eri; Yano, Keiichi; Iida, Shigeru; Satoh, Mitsuo

    2016-05-01

    The structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin-binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose type showed higher heparin-binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin-binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose type. In pharmacokinetic profiling, the high-mannose type showed a much shorter plasma half-life than the complex type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood. PMID:26747427

  11. Addition of Selenium Nanoparticles to Electrospun Silk Scaffold Improves the Mammalian Cell Activity While Reducing Bacterial Growth.

    PubMed

    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. 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

  13. 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. PMID:19883801

  14. The Cdk5 activator P39 specifically links muskelin to myosin II and regulates stress fiber formation and actin organization in lens.

    PubMed

    Tripathi, Brajendra K; Lowy, Douglas R; Zelenka, Peggy S

    2015-01-01

    Cyclin dependent kinase 5 (Cdk5), a proline-directed serine/threonine kinase, requires p39 for its enzymatic activity, and is implicated in cytoskeletal organization and contraction in numerous cell types. The C-terminus of p39 binds muskelin, a multi-domain scaffolding protein known to affect cytoskeletal organization, but the mechanisms by which muskelin affects cytoskeletal organization remain unclear. The present study sought to determine whether p39 might serve as an adaptor protein that links muskelin to stress fibers and to investigate the possible biological relevance of such an interaction. Double immunoprecipitation showed that muskelin, p39, and myosin II are components of a single intracellular complex, and suppressing p39 abrogated the interaction between muskelin and the myosin subunits, demonstrating that p39 is required to link muskelin to myosin II. Muskelin is colocalized with myosin regulatory light chain (MRLC) and on stress fibers. The suppression of muskelin reduced Rho-GTP, MRLC phosphorylation, disrupted stress fiber organization, and promoted cell migration, all of which closely mimic the effect of Cdk5 inhibition. Moreover, suppressing muskelin and inhibiting Cdk5 together have no additional effect, indicating that muskelin plays an important role in Cdk5-dependent signaling. p39 is necessary and sufficient for Cdk5-dependent regulation of MRLC phosphorylation, as suppression of p39, but not p35, reduces MRLC phosphorylation. Together, these results demonstrate that p39 specifically links muskelin to myosin II and consequently, to stress fibers and reveal a novel role for muskelin in regulating myosin phosphorylation and cytoskeletal organization. PMID:25128817

  15. The Cdk5 activator P39 specifically links muskelin to myosin II and regulates stress fiber formation and actin organization in lens.

    PubMed

    Tripathi, Brajendra K; Lowy, Douglas R; Zelenka, Peggy S

    2015-01-01

    Cyclin dependent kinase 5 (Cdk5), a proline-directed serine/threonine kinase, requires p39 for its enzymatic activity, and is implicated in cytoskeletal organization and contraction in numerous cell types. The C-terminus of p39 binds muskelin, a multi-domain scaffolding protein known to affect cytoskeletal organization, but the mechanisms by which muskelin affects cytoskeletal organization remain unclear. The present study sought to determine whether p39 might serve as an adaptor protein that links muskelin to stress fibers and to investigate the possible biological relevance of such an interaction. Double immunoprecipitation showed that muskelin, p39, and myosin II are components of a single intracellular complex, and suppressing p39 abrogated the interaction between muskelin and the myosin subunits, demonstrating that p39 is required to link muskelin to myosin II. Muskelin is colocalized with myosin regulatory light chain (MRLC) and on stress fibers. The suppression of muskelin reduced Rho-GTP, MRLC phosphorylation, disrupted stress fiber organization, and promoted cell migration, all of which closely mimic the effect of Cdk5 inhibition. Moreover, suppressing muskelin and inhibiting Cdk5 together have no additional effect, indicating that muskelin plays an important role in Cdk5-dependent signaling. p39 is necessary and sufficient for Cdk5-dependent regulation of MRLC phosphorylation, as suppression of p39, but not p35, reduces MRLC phosphorylation. Together, these results demonstrate that p39 specifically links muskelin to myosin II and consequently, to stress fibers and reveal a novel role for muskelin in regulating myosin phosphorylation and cytoskeletal organization.

  16. ADAM30 Downregulates APP-Linked Defects Through Cathepsin D Activation in Alzheimer's Disease.

    PubMed

    Letronne, Florent; Laumet, Geoffroy; Ayral, Anne-Marie; Chapuis, Julien; Demiautte, Florie; Laga, Mathias; Vandenberghe, Michel E; Malmanche, Nicolas; Leroux, Florence; Eysert, Fanny; Sottejeau, Yoann; Chami, Linda; Flaig, Amandine; Bauer, Charlotte; Dourlen, Pierre; Lesaffre, Marie; Delay, Charlotte; Huot, Ludovic; Dumont, Julie; Werkmeister, Elisabeth; Lafont, Franck; Mendes, Tiago; Hansmannel, Franck; Dermaut, Bart; Deprez, Benoit; Hérard, Anne-Sophie; Dhenain, Marc; Souedet, Nicolas; Pasquier, Florence; Tulasne, David; Berr, Claudine; Hauw, Jean-Jacques; Lemoine, Yves; Amouyel, Philippe; Mann, David; Déprez, Rebecca; Checler, Frédéric; Hot, David; Delzescaux, Thierry; Gevaert, Kris; Lambert, Jean-Charles

    2016-07-01

    Although several ADAMs (A disintegrin-like and metalloproteases) have been shown to contribute to the amyloid precursor protein (APP) metabolism, the full spectrum of metalloproteases involved in this metabolism remains to be established. Transcriptomic analyses centred on metalloprotease genes unraveled a 50% decrease in ADAM30 expression that inversely correlates with amyloid load in Alzheimer's disease brains. Accordingly, in vitro down- or up-regulation of ADAM30 expression triggered an increase/decrease in Aβ peptides levels whereas expression of a biologically inactive ADAM30 (ADAM30(mut)) did not affect Aβ secretion. Proteomics/cell-based experiments showed that ADAM30-dependent regulation of APP metabolism required both cathepsin D (CTSD) activation and APP sorting to lysosomes. Accordingly, in Alzheimer-like transgenic mice, neuronal ADAM30 over-expression lowered Aβ42 secretion in neuron primary cultures, soluble Aβ42 and amyloid plaque load levels in the brain and concomitantly enhanced CTSD activity and finally rescued long term potentiation alterations. Our data thus indicate that lowering ADAM30 expression may favor Aβ production, thereby contributing to Alzheimer's disease development. PMID:27333034

  17. ADAM30 Downregulates APP-Linked Defects Through Cathepsin D Activation in Alzheimer's Disease.

    PubMed

    Letronne, Florent; Laumet, Geoffroy; Ayral, Anne-Marie; Chapuis, Julien; Demiautte, Florie; Laga, Mathias; Vandenberghe, Michel E; Malmanche, Nicolas; Leroux, Florence; Eysert, Fanny; Sottejeau, Yoann; Chami, Linda; Flaig, Amandine; Bauer, Charlotte; Dourlen, Pierre; Lesaffre, Marie; Delay, Charlotte; Huot, Ludovic; Dumont, Julie; Werkmeister, Elisabeth; Lafont, Franck; Mendes, Tiago; Hansmannel, Franck; Dermaut, Bart; Deprez, Benoit; Hérard, Anne-Sophie; Dhenain, Marc; Souedet, Nicolas; Pasquier, Florence; Tulasne, David; Berr, Claudine; Hauw, Jean-Jacques; Lemoine, Yves; Amouyel, Philippe; Mann, David; Déprez, Rebecca; Checler, Frédéric; Hot, David; Delzescaux, Thierry; Gevaert, Kris; Lambert, Jean-Charles

    2016-07-01

    Although several ADAMs (A disintegrin-like and metalloproteases) have been shown to contribute to the amyloid precursor protein (APP) metabolism, the full spectrum of metalloproteases involved in this metabolism remains to be established. Transcriptomic analyses centred on metalloprotease genes unraveled a 50% decrease in ADAM30 expression that inversely correlates with amyloid load in Alzheimer's disease brains. Accordingly, in vitro down- or up-regulation of ADAM30 expression triggered an increase/decrease in Aβ peptides levels whereas expression of a biologically inactive ADAM30 (ADAM30(mut)) did not affect Aβ secretion. Proteomics/cell-based experiments showed that ADAM30-dependent regulation of APP metabolism required both cathepsin D (CTSD) activation and APP sorting to lysosomes. Accordingly, in Alzheimer-like transgenic mice, neuronal ADAM30 over-expression lowered Aβ42 secretion in neuron primary cultures, soluble Aβ42 and amyloid plaque load levels in the brain and concomitantly enhanced CTSD activity and finally rescued long term potentiation alterations. Our data thus indicate that lowering ADAM30 expression may favor Aβ production, thereby contributing to Alzheimer's disease development.

  18. Daily parental knowledge of youth activities is linked to youth physical symptoms and HPA functioning.

    PubMed

    Lippold, Melissa A; Davis, Kelly D; McHale, Susan M; Almeida, David M

    2016-03-01

    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 8 consecutive evenings. On 4 study days, cortisol samples were collected at 4 time points (waking, 30 min after waking, before dinner, bedtime). Multilevel 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 8-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

  19. 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.

  20. Microglial activation, recruitment and phagocytosis as linked phenomena in ferric oxide nanoparticle exposure.

    PubMed

    Wang, Yun; Wang, Bing; Zhu, Mo-Tao; Li, Ming; Wang, Hua-Jian; Wang, Meng; Ouyang, Hong; Chai, Zhi-Fang; Feng, Wei-Yue; Zhao, Yu-Liang

    2011-08-10

    Microglia as the resident macrophage-like cells in the central nervous system (CNS) play a pivotal role in the innate immune responses of CNS. Understanding the reactions of microglia cells to nanoparticle exposure is important in the exploration of neurobiology of nanoparticles. Here we provide a systemic mapping of microglia and the corresponding pathological changes in olfactory-transport related brain areas of mice with Fe(2)O(3)-nanoparticle intranasal treatment. We showed that intranasal exposure of Fe(2)O(3) nanoparticle could lead to pathological alteration in olfactory bulb, hippocampus and striatum, and caused microglial proliferation, activation and recruitment in these areas, especially in olfactory bulb. Further experiments with BV2 microglial cells showed the exposure to Fe(2)O(3) nanoparticles could induce cells proliferation, phagocytosis and generation of ROS and NO, but did not cause significant release of inflammatory factors, including IL-1β, IL-6 and TNF-α. Our results indicate that microglial activation may act as an alarm and defense system in the processes of the exogenous nanoparticles invading and storage in brain.

  1. 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

  2. Combined analysis of passive and active seismic measurements using additional geologic data for the determination of shallow subsurface structures

    NASA Astrophysics Data System (ADS)

    Horstmann, Tobias; Brüstle, Andrea; Spies, Thomas; Schlittenhardt, Jörg; Schmidt, Bernd

    2016-04-01

    A detailed knowledge of subsurface structure is essential for geotechnical projects and local seismic hazard analyses. Passive seismic methods like microtremor measurements are widely used in geotechnical practice, but limitations and developments are still in focus of scientific discussion. The presentation outlines microtremor measurements in the context of microzonation in the scale of districts or small communities. H/V measurements are used to identify zones with similar underground properties. Subsequently a shear wave velocity (Vs) depth profile for each zone is determined by array measurements at selected sites. To reduce possible uncertainties in dispersion curve analyses of passive array measurements and ambiguities within the inversion process, we conducted an additional active seismic experiment and included available geological information. The presented work is realized in the framework of the research project MAGS2 ("Microseismic Activity of Geothermal Systems") and deals with the determination of seismic hazard analysis at sites near deep geothermal power plants in Germany. The measurements were conducted in the Upper Rhine Graben (URG) and the Bavarian molasses, where geothermal power plants are in operation. The results of the H/V- and array-measurements in the region of Landau (URG) are presented and compared to known geological-tectonic structures. The H/V measurements show several zones with similar H/V-curves which indicate homogenous underground properties. Additionally to the passive seismic measurements an active refraction experiment was performed and evaluated using the MASW method („Multichannel Analysis of Surface Waves") to strengthen the determination of shear-wave-velocity depth profile. The dispersion curves for Rayleigh-waves of the active experiment support the Rayleigh-dispersion curves from passive measurements and therefore provide a valuable supplement. Furthermore, the Rayleigh-wave ellipticity was calculated to reduce

  3. 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

  4. 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. PMID:27093053

  5. 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.

  6. Effects of plasmochemical treatments and cerium additions on the structural characteristics and activity of copper catalyst particles in isopropanol dehydrogenation

    NASA Astrophysics Data System (ADS)

    Platonov, E. A.; Lobanov, N. N.; Galimova, N. A.; Protasova, I. A.; Yagodovskii, V. D.

    2012-08-01

    The effect of the treatment of the 5 wt % Cu/SiO2 (I) and (5 wt % Cu + 0.5 wt % Ce)/SiO2 (II) catalysts with glow discharge plasma in O2, H2, and Ar on their structural characteristics was studied by X-ray phase analysis; the influence of cerium additions and plasmochemical treatments on the catalyst activity in isopropanol dehydrogenation was also investigated. Under the plasmochemical treatment, the diameters of Cu particles in catalyst I nearly doubled and microstresses in the metal particles also changed. Catalyst II was X-ray amorphous both before and after plasmochemical treatments. The activity of I after plasmochemical treatment increased because of the increase in the number of centers and changes in their composition. Growth of the activity of I compared with the activity of II was explained by the formation of new catalytic centers due to positive charging of the Ce+α adatom on the surface of the copper particle.

  7. 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

  8. 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.

  9. Constraining the Lateral Helix of Respiratory Complex I by Cross-linking Does Not Impair Enzyme Activity or Proton Translocation*

    PubMed Central

    Zhu, Shaotong; Vik, Steven B.

    2015-01-01

    Complex I (NADH:ubiquinone oxidoreductase) is a multisubunit, membrane-bound enzyme of the respiratory chain. The energy from NADH oxidation in the peripheral region of the enzyme is used to drive proton translocation across the membrane. One of the integral membrane subunits, nuoL in Escherichia coli, has an unusual lateral helix of ∼75 residues that lies parallel to the membrane surface and has been proposed to play a mechanical role as a piston during proton translocation (Efremov, R. G., Baradaran, R., and Sazanov, L. A. (2010) Nature 465, 441–445). To test this hypothesis we have introduced 11 pairs of cysteine residues into Complex I; in each pair one is in the lateral helix, and the other is in a nearby region of subunit N, M, or L. The double mutants were treated with Cu2+ ions or with bi-functional methanethiosulfonate reagents to catalyze cross-link formation in membrane vesicles. The yields of cross-linked products were typically 50–90%, as judged by immunoblotting, but in no case did the activity of Complex I decrease by >10–20%, as indicated by deamino-NADH oxidase activity or rates of proton translocation. In contrast, several pairs of cysteine residues introduced at other interfaces of N:M and M:L subunits led to significant loss of activity, in particular, in the region of residue Glu-144 of subunit M. The results do not support the hypothesis that the lateral helix of subunit L functions like a piston, but rather, they suggest that conformational changes might be transmitted more directly through the functional residues of the proton translocation apparatus. PMID:26134569

  10. Site-directed mutagenesis of tobacco anionic peroxidase: Effect of additional aromatic amino acids on stability and activity.

    PubMed

    Poloznikov, A A; Zakharova, G S; Chubar, T A; Hushpulian, D M; Tishkov, V I; Gazaryan, I G

    2015-08-01

    Tobacco anionic peroxidase (TOP) is known to effectively catalyze luminol oxidation without enhancers, in contrast to horseradish peroxidase (HRP). To pursue structure-activity relationship studies for TOP, two amino acids have been chosen for mutation, namely Thr151, close to the heme plane, and Phe140 at the entrance to the active site pocket. Three mutant forms TOP F140Y, T151W and F140Y/T151W have been expressed in Escherichia coli, and reactivated to yield active enzymes. Single-point mutations introducing additional aromatic amino acid residues at the surface of TOP exhibit a significant effect on the enzyme catalytic activity and stability as judged by the results of steady-state and transient kinetics studies. TOP T151W is up to 4-fold more active towards a number of aromatic substrates including luminol, whereas TOP F140Y is 2-fold more stable against thermal inactivation and 8-fold more stable in the reaction course. These steady-state observations have been rationalized with the help of transient kinetic studies on the enzyme reaction with hydrogen peroxide in a single turnover regime. The stopped-flow data reveal (a) an increased stability of F140Y Compound I towards hydrogen peroxide, and thus, a higher operational stability as compared to the wild-type enzyme, and (b) a lesser leakage of oxidative equivalents from TOP T151W Compound I resulting in the increased catalytic activity. The results obtained show that TOP unique properties can be further improved for practical applications by site-directed mutagenesis.

  11. 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.

  12. 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.

  13. Adenosine: front and center in linking nutrition and metabolism to neuronal activity

    PubMed Central

    Greene, Robert W.

    2011-01-01

    Many individuals with epilepsy benefit from consuming a ketogenic diet, which is similar to the more commonly known Atkins diet. The underlying molecular reason for this has not been determined. However, in this issue of the JCI, Masino et al. have elucidated the mechanism responsible for the antiepileptic effects of the ketogenic diet in mice. The diet is shown to decrease expression of the enzyme adenosine kinase (Adk), which is responsible for clearing the endogenous antiepileptic agent adenosine (Ado) from the extracellular CNS space. Decreased expression of Adk results in increased extracellular Ado, activation of inhibitory Ado A1 receptors, and decreased seizure generation, the desired therapeutic effect. The authors’ work serves to emphasize the importance of controlling Adk expression, not only as the mechanism of action of the ketogenic diet, but also as a potential target of future therapies. PMID:21701073

  14. Executive function moderates the intention-behavior link for physical activity and dietary behavior.

    PubMed

    Hall, Peter A; Fong, Geoffrey T; Epp, Lynette J; Elias, Lorin J

    2008-01-01

    Dominant theories of health behavior posit that social-cognitive and conative variables are sufficient to explain health behavior tendencies. The current studies challenge this assumption in two ways: (1) by demonstrating that unique variance in health protective behavior is predictable by knowing about individual differences in executive functioning, and (2) by demonstrating that executive function moderates the association between intention and behavior. In Studies 1 and 2, participants completed a computer-based task of executive function (Go/NoGo task) and articulated 1-week behavioral intentions for physical activity (Study 1) and dietary behavior (Study 2). Hierarchical regression analyses revealed that executive function predicts unique variance in both behaviors, and strongly moderates the association between behavioral intention and behavioral performance. Together behavioral intention and executive function explain more variance in health protective behavior than 'rational actor' models that have been widely adopted and disseminated. PMID:25160480

  15. 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.

  16. Brown Adipose Tissue Activation Is Linked to Distinct Systemic Effects on Lipid Metabolism in Humans.

    PubMed

    Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Saraf, Manish K; Annamalai, Palam; Yfanti, Christina; Chao, Tony; Wong, Daniel; Shinoda, Kosaku; Labbė, Sebastien M; Hurren, Nicholas M; Cesani, Fernardo; Kajimura, Shingo; Sidossis, Labros S

    2016-06-14

    Recent studies suggest that brown adipose tissue (BAT) plays a role in energy and glucose metabolism in humans. However, the physiological significance of human BAT in lipid metabolism remains unknown. We studied 16 overweight/obese men during prolonged, non-shivering cold and thermoneutral conditions using stable isotopic tracer methodologies in conjunction with hyperinsulinemic-euglycemic clamps and BAT and white adipose tissue (WAT) biopsies. BAT volume was significantly associated with increased whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity. Functional analysis of BAT and WAT demonstrated the greater thermogenic capacity of BAT compared to WAT, while molecular analysis revealed a cold-induced upregulation of genes involved in lipid metabolism only in BAT. The accelerated mobilization and oxidation of lipids upon BAT activation supports a putative role for BAT in the regulation of lipid metabolism in humans. PMID:27238638

  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. 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. PMID:25573757

  19. 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

  20. 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

  1. Antimicrobial activity of lactoperoxidase system incorporated into cross-linked alginate films.

    PubMed

    Yener, Fatih Y G; Korel, Figen; Yemenicioğlu, Ahmet

    2009-03-01

    In this study, the antimicrobial effect of lactoperoxidase (LPS) incorporated alginate films was investigated on Escherichia coli (NRRL B-3008), Listeria innocua (NRRL B-33314), and Pseudomonas fluorescens (NRRL B-253) in presence of different concentrations of H(2)O(2) (0.2, 0.4, and 0.8 mM) and KSCN (1, 2, and 4 mM). The incorporation of 70 nmol ABTS/min/cm(2) LPS into alginate films gave 0.66 to 0.85 nmol ABTS/min/cm(2) enzyme activity at 0.2 to 0.8 mM H(2)O(2) concentration range. The antimicrobial activity of LPS system on target bacteria changed according to the concentrations of KSCN and H(2)O(2). The growth of all tested bacteria was prevented for a 6-h period by applying LPS system in presence of 0.4 or 0.8 mM H(2)O(2) and 4 mM KSCN. At 0.8 mM H(2)O(2) and 4 mM KSCN, the LPS system also inhibited growth of L. innocua and P. fluorescens for a 24-h incubation period, whereas E. coli growth could not be inhibited for 24 h under these conditions. At 0.2 mM H(2)O(2) and 1 to 4 mM KSCN, a considerable inhibitory effect was obtained only on P. fluorescens. The decreasing order of the resistance of studied bacteria to LPS system is as follows: E. coli, L. innocua, and P. fluorescens. The developed antimicrobial system has a good potential for use in meat, poultry, and seafood since alginate coatings are already used in these products. Further studies are needed to test the LPS incorporated edible films in real food systems.

  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. PMID:27625645

  3. 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.

  4. Recognition of Lys48-Linked Di-ubiquitin and Deubiquitinating Activities of the SARS Coronavirus Papain-like Protease.

    PubMed

    Békés, Miklós; van der Heden van Noort, Gerbrand J; Ekkebus, Reggy; Ovaa, Huib; Huang, Tony T; Lima, Christopher D

    2016-05-19

    Deubiquitinating enzymes (DUBs) recognize and cleave linkage-specific polyubiquitin (polyUb) chains, but mechanisms underlying specificity remain elusive in many cases. The severe acute respiratory syndrome (SARS) coronavirus papain-like protease (PLpro) is a DUB that cleaves ISG15, a two-domain Ub-like protein, and Lys48-linked polyUb chains, releasing diUb(Lys48) products. To elucidate this specificity, we report the 2.85 Å crystal structure of SARS PLpro bound to a diUb(Lys48) activity-based probe. SARS PLpro binds diUb(Lys48) in an extended conformation via two contact sites, S1 and S2, which are proximal and distal to the active site, respectively. We show that specificity for polyUb(Lys48) chains is predicated on contacts in the S2 site and enhanced by an S1-S1' preference for a Lys48 linkage across the active site. In contrast, ISG15 specificity is dominated by contacts in the S1 site. Determinants revealed for polyUb(Lys48) specificity should prove useful in understanding PLpro deubiquitinating activities in coronavirus infections. PMID:27203180

  5. Ventral Tegmental Area Neurotensin Signaling Links the Lateral Hypothalamus to Locomotor Activity and Striatal Dopamine Efflux in Male Mice

    PubMed Central

    Patterson, Christa M.; Wong, Jenny-Marie T.; Leinninger, Gina M.; Allison, Margaret B.; Mabrouk, Omar S.; Kasper, Chelsea L.; Gonzalez, Ian E.; Mackenzie, Alexander; Jones, Justin C.

    2015-01-01

    Projections from the lateral hypothalamic area (LHA) innervate components of the mesolimbic dopamine (MLDA) system, including the ventral tegmental area (VTA) and nucleus accumbens (NAc), to modulate motivation appropriately for physiologic state. Neurotensin (NT)-containing LHA neurons respond to multiple homeostatic challenges and project to the VTA, suggesting that these neurons could link such signals to MLDA function. Indeed, we found that pharmacogenetic activation of LHA NT neurons promoted prolonged DA-dependent locomotor activity and NAc DA efflux, suggesting the importance of VTA neurotransmitter release by LHA NT neurons for the control of MLDA function. Using a microdialysis-mass spectrometry technique that we developed to detect endogenous NT in extracellular fluid in the mouse brain, we found that activation of LHA NT cells acutely increased the extracellular concentration of NT (a known activator of VTA DA cells) in the VTA. In contrast to the prolonged elevation of extracellular NAc DA, however, VTA NT concentrations rapidly returned to baseline. Intra-VTA infusion of NT receptor antagonist abrogated the ability of LHA NT cells to increase extracellular DA in the NAc, demonstrating that VTA NT promotes NAc DA release. Thus, transient LHA-derived NT release in the VTA couples LHA signaling to prolonged changes in DA efflux and MLDA function. PMID:25734363

  6. Prolonged activation of the hypothalamus-pituitary-gonadal axis in a child with X-linked adrenal hypoplasia congenita.

    PubMed

    Takahashi, I; Takahashi, T; Shoji, Y; Takada, G

    2000-07-01

    X-linked adrenal hypoplasia congenita (AHC) is a rare developmental disorder of the human adrenal cortex that is caused by a mutation of the DAX-1 gene, a member of the nuclear hormone receptor superfamily. Hypogonadotrophic hypogonadism is frequently associated with this disease and the DAX-1 mutation is known to impair gonadotrophin production by acting at both the hypothalamic and pituitary levels. However, three recent studies reported that the hypothalamic-pituitary-gonadal axis was active in six infants with AHC, suggesting that a difference exists in the central regulation of hypothalamic-pituitary-gonadal activity between infant boys and pubertal boys. To determine the effect of the DAX-1 gene mutation on the axis in early childhood, we measured testosterone, LH, and FSH and performed LH-releasing hormone tests on a boy with AHC from birth to 3 years of age. Surprisingly, our findings showed that the axis was active from the infantile period to 3 years of age. This delayed initiation of the prepubertal pause, or prolonged activation of the axis, indicates that the DAX-1 gene is related to the control mechanism of the prepubertal restraint of gonadotrophin secretion.

  7. 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.

  8. 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

  9. Membrane-to-nucleus signaling links insulin-like growth factor-1- and stem cell factor-activated pathways.

    PubMed

    Hayashi, Yujiro; Asuzu, David T; Gibbons, Simon J; Aarsvold, Kirsten H; Bardsley, Michael R; Lomberk, Gwen A; Mathison, Angela J; Kendrick, Michael L; Shen, K Robert; Taguchi, Takahiro; Gupta, Anu; Rubin, Brian P; Fletcher, Jonathan A; Farrugia, Gianrico; Urrutia, Raul A; Ordog, Tamas

    2013-01-01

    Stem cell factor (mouse: Kitl, human: KITLG) and insulin-like growth factor-1 (IGF1), acting via KIT and IGF1 receptor (IGF1R), respectively, are critical for the development and integrity of several tissues. Autocrine/paracrine KITLG-KIT and IGF1-IGF1R signaling are also activated in several cancers including gastrointestinal stromal tumors (GIST), the most common sarcoma. In murine gastric muscles, IGF1 promotes Kitl-dependent development of interstitial cells of Cajal (ICC), the non-neoplastic counterpart of GIST, suggesting cooperation between these pathways. Here, we report a novel mechanism linking IGF1-IGF1R and KITLG-KIT signaling in both normal and neoplastic cells. In murine gastric muscles, the microenvironment for ICC and GIST, human hepatic stellate cells (LX-2), a model for cancer niches, and GIST cells, IGF1 stimulated Kitl/KITLG protein and mRNA expression and promoter activity by activating several signaling pathways including AKT-mediated glycogen synthase kinase-3β inhibition (GSK3i). GSK3i alone also stimulated Kitl/KITLG expression without activating mitogenic pathways. Both IGF1 and GSK3i induced chromatin-level changes favoring transcriptional activation at the Kitl promoter including increased histone H3/H4 acetylation and H3 lysine (K) 4 methylation, reduced H3K9 and H3K27 methylation and reduced occupancy by the H3K27 methyltransferase EZH2. By pharmacological or RNA interference-mediated inhibition of chromatin modifiers we demonstrated that these changes have the predicted impact on KITLG expression. KITLG knock-down and immunoneutralization inhibited the proliferation of GIST cells expressing wild-type KIT, signifying oncogenic autocrine/paracrine KITLG-KIT signaling. We conclude that membrane-to-nucleus signaling involving GSK3i establishes a previously unrecognized link between the IGF1-IGF1R and KITLG-KIT pathways, which is active in both physiologic and oncogenic contexts and can be exploited for therapeutic purposes. PMID:24116170

  10. The effects of mediator and granular activated carbon addition on degradation of trace organic contaminants by an enzymatic membrane reactor.

    PubMed

    Nguyen, Luong N; Hai, Faisal I; Price, William E; Leusch, Frederic D L; Roddick, Felicity; Ngo, Hao H; Guo, Wenshan; Magram, Saleh F; Nghiem, Long D

    2014-09-01

    The removal of four recalcitrant trace organic contaminants (TrOCs), namely carbamazepine, diclofenac, sulfamethoxazole and atrazine by laccase in an enzymatic membrane reactor (EMR) was studied. Laccases are not effective for degrading non-phenolic compounds; nevertheless, 22-55% removal of these four TrOCs was achieved by the laccase EMR. Addition of the redox-mediator syringaldehyde (SA) to the EMR resulted in a notable dose-dependent improvement (15-45%) of TrOC removal affected by inherent TrOC properties and loading rates. However, SA addition resulted in a concomitant increase in the toxicity of the treated effluent. A further 14-25% improvement in aqueous phase removal of the TrOCs was consistently observed following a one-off dosing of 3g/L granular activated carbon (GAC). Mass balance analysis reveals that this improvement was not due solely to adsorption but also enhanced biodegradation. GAC addition also reduced membrane fouling and the SA-induced toxicity of the effluent. PMID:24980029

  11. Structure activity relationship of pyridoxazinone substituted RHS analogs of oxabicyclooctane-linked 1,5-naphthyridinyl novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-6).

    PubMed

    Singh, Sheo B; Kaelin, David E; Wu, Jin; Miesel, Lynn; Tan, Christopher M; Meinke, Peter T; Olsen, David B; Lagrutta, Armando; Wei, Changqing; Liao, Yonggang; Peng, Xuanjia; Wang, Xiu; Fukuda, Hideyuki; Kishii, Ryuta; Takei, Masaya; Yajima, Masanobu; Shibue, Taku; Shibata, Takeshi; Ohata, Kohei; Nishimura, Akinori; Fukuda, Yasumichi

    2015-09-01

    Oxabicyclooctane linked 1,5-naphthyridinyl-pyridoxazinones are novel broad-spectrum bacterial topoisomerase inhibitors (NBTIs) targeting bacterial DNA gyrase and topoisomerase IV at a site different than quinolones. Due to lack of cross-resistance to known antibiotics they present excellent opportunity to combat drug-resistant bacteria. A structure activity relationship of the pyridoxazinone moiety is described in this Letter. Chemical synthesis and activities of NBTIs with substitutions at C-3, C-4 and C-7 of the pyridoxazinone moiety with halogens, alkyl groups and methoxy group has been described. In addition, substitutions of the linker NH proton and its transformation into amide analogs of AM-8085 and AM-8191 have been reported. Fluoro, chloro, and methyl groups at C-3 of the pyridoxazinone moiety retained the potency and spectrum. In addition, a C-3 fluoro analog showed 4-fold better oral efficacy (ED50 3.9 mg/kg) as compared to the parent AM-8085 in a murine bacteremia model of infection of Staphylococcus aureus. Even modest polarity (e.g., methoxy) is not tolerated at C-3 of the pyridoxazinone unit. The basicity and NH group of the linker is important for the activity when CH2 is at the linker position-8. However, amides (with linker position-8 ketone) with a position-7 NH or N-methyl group retained potency and spectrum suggesting that neither basicity nor hydrogen-donor properties of the linker amide NH is essential for the activity. This would suggest likely an altered binding mode of the linker position-7,8 amide containing compounds. The amides showed highly improved hERG (functional IC50 >30 μM) profile.

  12. 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

  13. 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.

  14. Parental knowledge of adolescent activities: links with parental attachment style and adolescent substance use.

    PubMed

    Jones, Jason D; Ehrlich, Katherine B; Lejuez, C W; Cassidy, Jude

    2015-04-01

    Parents' knowledge of their adolescents' whereabouts and activities is a robust predictor of adolescent risk behavior, including the use of drugs and alcohol. Surprisingly few studies have attempted to identify parental characteristics that are associated with the degree of parental knowledge. The present study is the first to examine how parental attachment style relates to mother, father, and adolescent reports of parental knowledge. Further, we used structural equation modeling to test the associations among parents' attachment styles, reports of parental knowledge, and adolescents' alcohol and marijuana use. Participants included 203 adolescents (M age = 14.02, SD = .91) living in 2-parent households and their parent(s). As predicted, mothers' and fathers' insecure attachment styles were negatively associated with self-reported and adolescent-reported parental knowledge, and all 3 reports of parental knowledge were negatively related to adolescent substance use. Mothers' and fathers' attachment styles were unrelated to adolescent substance use. However, evidence emerged for indirect effects of parental attachment style on adolescent substance use through reports of parental knowledge. Implications for prevention efforts and the importance of multiple reporters within the family are discussed.

  15. Parental Knowledge of Adolescent Activities: Links with Parental Attachment Style and Adolescent Substance Use

    PubMed Central

    Jones, Jason D.; Ehrlich, Katherine B.; Lejuez, C. W.; Cassidy, Jude

    2015-01-01

    Parents’ knowledge of their adolescents’ whereabouts and activities is a robust predictor of adolescent risk behavior, including the use of drugs and alcohol. Surprisingly few studies have attempted to identify parental characteristics that are associated with the degree of parental knowledge. The present study is the first to examine how parental attachment style relates to mother, father, and adolescent reports of parental knowledge. Further, we used structural equation modeling to test the associations among parents’ attachment styles, reports of parental knowledge, and adolescents’ alcohol and marijuana use. Participants included 203 adolescents (mean age = 14.02, SD = .91) living in two-parent households and their parent(s). As predicted, mothers’ and fathers’ insecure attachment styles were negatively associated with self-reported and adolescent-reported parental knowledge, and all three reports of parental knowledge were negatively related to adolescent substance use. Mothers’ and fathers’ attachment styles were unrelated to adolescent substance use. However, evidence emerged for indirect effects of parental attachment style on adolescent substance use through reports of parental knowledge. Implications for prevention efforts and the importance of multiple reporters within the family are discussed. PMID:25730406

  16. 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.

  17. Phosphopeptide binding by Sld3 links Dbf4-dependent kinase to MCM replicative helicase activation.

    PubMed

    Deegan, Tom D; Yeeles, Joseph Tp; Diffley, John Fx

    2016-05-01

    The initiation of eukaryotic DNA replication requires the assembly of active CMG (Cdc45-MCM-GINS) helicases at replication origins by a set of conserved and essential firing factors. This process is controlled during the cell cycle by cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK), and in response to DNA damage by the checkpoint kinase Rad53/Chk1. Here we show that Sld3, previously shown to be an essential CDK and Rad53 substrate, is recruited to the inactive MCM double hexamer in a DDK-dependent manner. Sld3 binds specifically to DDK-phosphorylated peptides from two MCM subunits (Mcm4, 6) and then recruits Cdc45. MCM mutants that cannot bind Sld3 or Sld3 mutants that cannot bind phospho-MCM or Cdc45 do not support replication. Moreover, phosphomimicking mutants in Mcm4 and Mcm6 bind Sld3 without DDK and facilitate DDK-independent replication. Thus, Sld3 is an essential "reader" of DDK phosphorylation, integrating signals from three distinct protein kinase pathways to coordinate DNA replication during S phase. PMID:26912723

  18. Linking the fate of massive black hole binaries to the active galactic nuclei luminosity function

    NASA Astrophysics Data System (ADS)

    Dotti, M.; Merloni, A.; Montuori, C.

    2015-04-01

    Massive black hole binaries are naturally predicted in the context of the hierarchical model of structure formation. The binaries that manage to lose most of their angular momentum can coalesce to form a single remnant. In the last stages of this process, the holes undergo an extremely loud phase of gravitational wave emission, possibly detectable by current and future probes. The theoretical effort towards obtaining a coherent physical picture of the binary path down to coalescence is still underway. In this paper, for the first time, we take advantage of observational studies of active galactic nuclei evolution to constrain the efficiency of gas-driven binary decay. Under conservative assumptions we find that gas accretion towards the nuclear black holes can efficiently lead binaries of any mass forming at high redshift (≳2) to coalescence within the current time. The observed `downsizing' trend of the accreting black hole luminosity function further implies that the gas inflow is sufficient to drive light black holes down to coalescence, even if they bind in binaries at lower redshifts, down to z ≈ 0.5 for binaries of ˜107 M⊙, and z ≈ 0.2 for binaries of ˜106 M⊙. This has strong implications for the detection rates of coalescing black hole binaries of future space-based gravitational wave experiments.

  19. 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.

  20. 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

  1. 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. PMID:26676400

  2. 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

  3. An Observed Link between Active Galactic Nuclei and Violent Disk Instabilities in High-redshift Galaxies

    NASA Astrophysics Data System (ADS)

    Bournaud, Frédéric; Juneau, Stéphanie; Le Floc'h, Emeric; Mullaney, James; Daddi, Emanuele; Dekel, Avishai; Duc, Pierre-Alain; Elbaz, David; Salmi, Fadia; Dickinson, Mark

    2012-09-01

    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 108-109 M ⊙ 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 ~ 0.7. The majority of clumpy disks in our sample have a high probability of containing AGNs. Their [O III] λ5007 emission line is strongly excited, inconsistent with low-metallicity star formation (SF) alone. [Ne III] λ3869 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 1043 erg s-1, BH growth rates \\dot{m}_BH \\sim 10^{-2}\\,M_\\odot yr-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 SF and of BH growth.

  4. 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

  5. [Hospital pharmacist has a rule for best practice use and French hospital activity tariffs. Example of a pharmaceutical quality control for drugs reimbursed in addition of DRGs].

    PubMed

    Hedoux, S; Dode, X; Pivot, C; Couray-Targe, S; Aulagner, G

    2012-07-01

    The best practice contract has given a new objective to the hospital pharmacists for the reimbursement in addition to Diagnosis Related Groups' (DRGs) tariffs. We built our pharmaceutical quality control for the administration traceability follow-up regarding the DRGs and the cost of care, for two reasons: the nominal drugs dispensation in link with the prescription made by pharmacist and the important expenditure of these drugs. Our organization depends on the development level of the informatized drugs circuit and minimizes the risk of financial shortfalls or wrong benefits, possible causes of economic penalties for our hospital. On the basis of this follow-up, we highlighted our activity and identified problems of management and drugs circuit organization. The quality of the administration traceability impacts directly on the quality of the medical records and the reimbursements of the expensive drugs. A better knowledge of prescription software is also required for a better quality and security of the medical data used in the medical informatic systems. The drugs management and the personal treatment in and between the care units need to be improved too. We have to continue and improve our organization with the future financial model for ATU drugs and the FIDES project. The health personnel awareness and the development of best informatic tools are also required. PMID:22818260

  6. Is ozone pre-conditioning effect linked to Nrf2/EpRE activation pathway in vivo? A preliminary result.

    PubMed

    Re, Lamberto; Martínez-Sánchez, Gregorio; Bordicchia, Marica; Malcangi, Giuseppe; Pocognoli, Antonella; Morales-Segura, Miguel Angel; Rothchild, John; Rojas, Armando

    2014-11-01

    The present preliminary study has been focused on verifying whether ozone preconditioning may be linked to Nrf2/EpRE (nuclear factor erythroid 2/electrophile-responsive element) activation pathway in vivo. Healthy volunteers received a total of three Major Auto-Hemotherapy (MAH) treatments, with treatments administered every second day. The amount of blood used for each subject was standardized to the value obtained multiplying the subject׳s body weight by 1.3 in order to ensure the same ozone concentrations for each subject. A parallel group (n=50) age and gender matched was used as reference for the experimental variables related to the oxidative stress parameters. Levels of Nrf2 and oxidative stress index were measured throughout the study. Levels of Nrf2 (P<0.01) in peripheral blood mononuclear cells (PBMC) were found to increase immediately after ozone/oxygen exposure (35µg/ml, prior to reinfusion). This effect was still detected (P<0.05) in total circulating PBMC when measured 30min following reinfusion. After a series of 3 MAH, Nrf2 returned back to the basal level. At the end of the experiment the activities of superoxide dismutase and catalase were increased (P<0.05). These data demonstrate for the first time in vivo the activation of the Nrf2 pathway by a low dose of ozone and the promotion of the feedback mechanism that induces the synthesis of proteins which collectively favors cell survival.

  7. Long-term Results of a First-Generation Annealed Highly Cross-Linked Polyethylene in Young, Active Patients.

    PubMed

    Ranawat, Chitranjan S; Ranawat, Amar S; Ramteke, Alankar A; Nawabi, Danyal; Meftah, Morteza

    2016-01-01

    The survivorship of total hip arthroplasty in younger patients is dependent on the wear characteristics of the bearing surfaces. Long-term results with conventional polyethylene in young patients show a high failure rate. This study assessed the long-term results of a first-generation annealed highly cross-linked polyethylene (HCLPE) in uncemented total hip arthroplasty in young, active patients. Between 1999 and 2003, 112 total hip arthroplasty procedures performed in 91 patients with an average University of California Los Angeles activity score of 8 and mean age of 53 years (range, 24-65 years) were included from a prospective database. In all patients, a 28-mm metal femoral head on annealed HCLPE (Crossfire; Stryker, Mahwah, New Jersey) was used. At minimum 10-year follow-up (11.5±0.94 years), Kaplan-Meier survivorship was 97% for all failures (1 periprosthetic infection and 1 late dislocation) and 100% for mechanical failure (no revisions for osteolysis or loosening). This study showed low revision rates for wear-related failure and superior survivorship in young, active patients. Oxidation causing failure of the locking mechanism has not been a problem with Crossfire for up to 10 years. PMID:26811959

  8. Oocyte activation and latent HIV-1 reactivation: AMPK as a common mechanism of action linking the beginnings of life and the potential eradication of HIV-1.

    PubMed

    Finley, Jahahreeh

    2016-08-01

    stress (e.g. increase in Ca(2+) concentration, reactive oxygen species generation, increase in AMP/ATP ratio) is essential for oocyte maturation, T cell activation, and mitochondrial function. In addition to the AMPK kinase LKB1, CaMKK2, a Ca(2+)/calmodulin-dependent kinase that also activates AMPK, is present in and activated on T cell activation and is also present in mouse oocytes and persists until the zygote and two-cell stages. It is our hypothesis that AMPK activation represents a central node linking T cell activation-induced latent HIV-1 reactivation and both physiological and artificial oocyte activation. We further propose the novel observation that various compounds that have been shown to reactivate latent HIV-1 (e.g. PMA, ionomycin, metformin, bryostatin, resveratrol, etc.) or activate oocytes (PMA, ionomycin, ethanol, puromycin, etc.) either alone or in combination likely do so via stress-induced activation of AMPK. PMID:27372854

  9. Utility of a redox-active pyridine(diimine) chelate in facilitating two electron oxidative addition chemistry at uranium.

    PubMed

    Kiernicki, John J; Fanwick, Phillip E; Bart, Suzanne C

    2014-08-01

    Exposure of the uranium(IV) complex, Cp(P)U((Mes)PDI(Me)) (1) ((Mes)PDI(Me) = 2,6-((Mes)N=CMe)2–C5H3N; Mes = 2,4,6-trimethylphenyl; Cp(P) = 1-(7,7-dimethylbenzyl)cyclopentadienyl), which contains a [(Mes)PDI(Me)](3−) chelate, to I2, Cl2, PhSeCl, and PhEEPh (E = S, Se, Te) results in oxidative addition to form the uranium(IV) family, Cp(P)U(XX′)((Mes)PDI(Me)) (X = X′ = I, Cl, EPh; X = SePh, X′ = Cl). Spectroscopic and structural studies support products with [(Mes)PDI(Me)](1−), indicating the reducing equivalents derive from this redox-active chelate.

  10. The somatic hypermutation activity of a follicular lymphoma links to large insertions and deletions of immunoglobulin genes.

    PubMed

    Wu, H Y; Kaartinen, M

    1995-07-01

    A biopsy specimen from a patient with follicular lymphoma was divided into two fragments. DNA was extracted from one fragment and a 1.2 kb region of the functional heavy chain (IgH) gene was amplified, cloned and sequenced (eight clones). From the other fragment a cell line (HF-1) was started. The IgH gene region was amplified from the cell line, and sequenced without cloning. The nine sequences obtained could be arranged into a genealogical tree where the individual sequences differed from the deduced ancestor by 16-29 single nucleotide changes, some also by an insertion and/or a deletion. It is apparent that the sequence alterations were caused by somatic mutations during the growth of the lymphoma. The comparison of the sequences with two published (allelic) germline sequences of the human JH region showed approximately 20% non-homology. The differences included five additional multinucleotide insertion/deletion changes, the longest of them a 101-nucleotide insertion. Two long insertions were homologous to the adjacent germline sequences. We propose that most of the changes observed, including long deletions and insertions, represent or are linked to somatic hypermutation events of the Ig gene type. Although in a few cases large deletions and insertions (> 2 bp) have been found in mutated immunoglobulin genes, our results, for the first time, firmly link these deletions/insertions to somatic hypermutations; their frequency was found to be 2.2% of the observed mutational events in the non-translated gene regions. HF-1 is the first follicular lymphoma line successfully established from a lymphoma known to have hypermutated its Ig genes during the malignant growth. It is a candidate cell line to be studied for its ability to generate mutations of B cell type in cell cultures.

  11. 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.

  12. Suppression of activation energy and superconductivity by the addition of Al{sub 2}O{sub 3} nanoparticles in CuTl-1223 matrix

    SciTech Connect

    Jabbar, Abdul; Qasim, Irfan; Mumtaz, M.; Zubair, M.; Nadeem, K.; Khurram, A. A.

    2014-05-28

    Low anisotropic (Cu{sub 0.5}Tl{sub 0.5})Ba{sub 2}Ca{sub 2}Cu{sub 3}O{sub 10−δ} (CuTl-1223) high T{sub c} superconducting matrix was synthesized by solid-state reaction and Al{sub 2}O{sub 3} nanoparticles were prepared separately by co-precipitation method. Al{sub 2}O{sub 3} nanoparticles were added with different concentrations during the final sintering cycle of CuTl-1223 superconducting matrix to get the required (Al{sub 2}O{sub 3}){sub y}/CuTl-1223, y = 0.0, 0.5, 0.7, 1.0, and 1.5 wt. %, composites. The samples were characterized by X-ray diffraction (XRD), scanning electron microscopy, energy dispersive X-ray, and dc-resistivity (ρ) measurements. The activation energy and superconductivity were suppressed with increasing concentration of Al{sub 2}O{sub 3} nanoparticles in (CuTl-1223) matrix. The XRD analysis showed that the addition of Al{sub 2}O{sub 3} nanoparticles did not affect the crystal structure of the parent CuTl-1223 superconducting phase. The suppression of activation energy and superconducting properties is most probably due to weak flux pinning in the samples. The possible reason of weak flux pinning is reduction of weak links and enhanced inter-grain coupling due to the presence of Al{sub 2}O{sub 3} nanoparticles at the grain boundaries. The presence of Al{sub 2}O{sub 3} nanoparticles at the grain boundaries possibly reduced the number of flux pinning centers, which were present in the form of weak links in the pure CuTl-1223 superconducting matrix. The increase in the values of inter-grain coupling (α) deduced from the fluctuation induced conductivity analysis with the increased concentration of Al{sub 2}O{sub 3} nanoparticles is a theoretical evidence of improved inter-grain coupling.

  13. Oxidative Addition of Carbon–Carbon Bonds with a Redox-Active Bis(imino)pyridine Iron Complex

    PubMed Central

    Darmon, Jonathan M.; Stieber, S. Chantal E.; Sylvester, Kevin T.; Fernández, Ignacio; Lobkovsky, Emil; Semproni, Scott P.; Bill, Eckhard; Wieghardt, Karl; DeBeer, Serena; Chirik, Paul J.

    2013-01-01

    Addition of biphenylene to the bis(imino)pyridine iron dinitrogen complexes, (iPrPDI)Fe(N2)2 and [(MePDI)Fe(N2)]2(μ2-N2) (RPDI = 2,6-(2,6-R2—C6H3— N=CMe)2C5H3N; R = Me, iPr), resulted in oxidative addition of a C—C bond at ambient temperature to yield the corresponding iron biphenyl compounds, (RPDI)Fe-(biphenyl). The molecular structures of the resulting bis-(imino)pyridine iron metallacycles were established by X-ray diffraction and revealed idealized square pyramidal geometries. The electronic structures of the compounds were studied by Mössbauer spectroscopy, NMR spectroscopy, magnetochemistry, and X-ray absorption and X-ray emission spectroscopies. The experimental data, in combination with broken-symmetry density functional theory calculations, established spin crossover (low to intermediate spin) ferric compounds antiferromagnetically coupled to bis(imino)pyridine radical anions. Thus, the overall oxidation reaction involves cooperative electron loss from both the iron center and the redox-active bis(imino)pyridine ligand. PMID:23043331

  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. 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

  16. Appropriate Fe (II) Addition Significantly Enhances Anaerobic Ammonium Oxidation (Anammox) Activity through Improving the Bacterial Growth Rate

    NASA Astrophysics Data System (ADS)

    Liu, Yiwen; Ni, Bing-Jie

    2015-02-01

    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.

  17. Appropriate Fe (II) addition significantly enhances anaerobic ammonium oxidation (Anammox) activity through improving the bacterial growth rate.

    PubMed

    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

  18. 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. PMID:27080407

  19. Self-determined motivation in physical education and its links to motivation for leisure-time physical activity, physical activity, and well-being in general.

    PubMed

    Bagøien, Tor Egil; Halvari, Hallgeir; Nesheim, Hallgeir

    2010-10-01

    The present study tested a trans-contextual model based on self-determination theory of the relations between motivation in physical education, motivation in leisure-time physical activity, physical activity, and psychological well-being. Participants were 329 Norwegian upper secondary school students (M age = 16.5 yr., SD = 0.7). Students' perceptions of autonomy-supportive teachers in physical education were expected to be positively associated with students' psychological needs satisfaction in physical education, which was expected to be positively related to autonomous motivation for physical education participation. In turn, autonomous motivation for physical education was expected to be positively associated with perceived competence and autonomous motivation for leisure-time physical activity, which both were expected to be positively associated with leisure-time physical activity and psychological well-being in general. Structural equation models and bootstrapping supported the hypotheses and the indirect links between variables. Sex differences indicate that more research is needed on how to motivate girls to be more physically active in leisure time.

  20. A requirement of serotonergic p38α mitogen-activated protein kinase for peripheral immune system activation of CNS serotonin uptake and serotonin-linked behaviors

    PubMed Central

    Baganz, N L; Lindler, K M; Zhu, C B; Smith, J T; Robson, M J; Iwamoto, H; Deneris, E S; Hewlett, W A; Blakely, R D

    2015-01-01

    Alterations in central serotonin (5-hydroxytryptamine, 5-HT) neurotransmission and peripheral immune activation have been linked to multiple neuropsychiatric disorders, including depression, schizophrenia and autism. The antidepressant-sensitive 5-HT transporter (SERT, SLC6A4), a critical determinant of synaptic 5-HT inactivation, can be regulated by pro-inflammatory cytokine signaling. Systemic innate immune system activation via intraperitoneal lipopolysaccharide (LPS) injection rapidly elevates brain SERT activity and 5-HT clearance. Moreover, the pro-inflammatory cytokine interleukin (IL)-1β rapidly stimulates SERT activity in raphe nerve terminal preparations ex vivo, effects that are attenuated by pharmacological p38 MAPK inhibition. To establish a role of serotonergic p38α MAPK signaling in LPS/IL-1β-induced SERT regulation and attendant behavioral responses, we pursued studies in mice that afford conditional elimination of p38α MAPK in 5-HT neurons (p38α5HT−). We found p38α5HT− and control (p38α5HT+) littermates to be indistinguishable in viability and growth and to express equivalent levels of SERT protein and synaptosomal 5-HT transport activity. Consistent with pharmacological studies, however, IL-1β fails to increase SERT activity in midbrain synaptosomes prepared from p38α5HT− animals. Moreover, although LPS elevated plasma corticosterone and central/peripheral pro-inflammatory cytokines in p38α5HT− animals, elevations in midbrain SERT activity were absent nor were changes in depressive and anxiety-like behaviors observed. Our studies support an obligate role of p38α MAPK signaling in 5-HT neurons for the translation of immune activation to SERT regulation and 5-HT-modulated behaviors. PMID:26529424

  1. Metabolic Profiles and Genetic Diversity of Denitrifying Communities in Activated Sludge after Addition of Methanol or Ethanol†

    PubMed Central

    Hallin, Sara; Throbäck, Ingela Noredal; Dicksved, Johan; Pell, Mikael

    2006-01-01

    External carbon sources can enhance denitrification rates and thus improve nitrogen removal in wastewater treatment plants. The effects of adding methanol and ethanol on the genetic and metabolic diversity of denitrifying communities in activated sludge were compared using a pilot-scale plant with two parallel lines. A full-scale plant receiving the same municipal wastewater, but without external carbon source addition, was the reference. Metabolic profiles obtained from potential denitrification rates with 10 electron donors showed that the denitrifying communities altered their preferences for certain compounds after supplementation with methanol or ethanol and that methanol had the greater impact. Clone libraries of nirK and nirS genes, encoding the two different nitrite reductases in denitrifiers, revealed that methanol also increased the diversity of denitrifiers of the nirS type, which indicates that denitrifiers favored by methanol were on the rise in the community. This suggests that there might be a niche differentiation between nirS and nirK genotypes during activated sludge processes. The composition of nirS genotypes also varied greatly among all samples, whereas the nirK communities were more stable. The latter was confirmed by denaturing gradient gel electrophoresis of nirK communities on all sampling occasions. Our results support earlier hypotheses that the compositions of denitrifier communities change during predenitrification processes when external carbon sources are added, although no severe effect could be observed from an operational point of view. PMID:16885297

  2. 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. PMID:26783836

  3. 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.

  4. Non-Additive Voltametric Currents From a Mixture of Two, Three and Four Redox-Active Compounds and Electroanalytical Implications

    NASA Technical Reports Server (NTRS)

    Dass, Amala; Oh, Woon Su; Gao, Xue-Rong; Rawashdeh, Abdel M.; Leventis, Nicholas

    2004-01-01

    We have published recently the effect of dissimilar diffusion coefficients on the size of the voltammetric waves from a mixture of two redox-active compounds. Similarly, at the potential range where three redox-active species, decamethylferrocene (dMeFc), ferrocene (Fc) and N-methylphenothiazine (MePTZ), are oxidized simultaneously with rates controlled by linear diffusion, electrogenerated radicals diffusing outwards from the electrode react with the original species diffusing towards the electrode from the bulk; thus, Fc(+) reacts with dMeFc producing Fc and dMeFc(+), while MePTZ(+) reacts both with dMeFc producing MePTZ and dMeFc(+), and with Fc producing MePTZ and Fc(+). These reactions replace dMeFc with Fc at the second plateau, and both dMeFc and Fc with MePTZ at the third plateau. Since the diffusion coefficients of the three species are not equal, the mass-transfer limited currents of the second and the third oxidation wave plateaus change by approx. 10%. Numerical simulations of the experimental voltamograms support this mechanism. Similar results were also obtained for a mixture of four redoxactive compounds. The implications of this non-additive nature of currents on: (a) the use of internal voltammetric standards for quantitative analysis of a mixture of redox-active compounds; and, (b) the half wave potentials (E1/2) of the 2nd, 3rd and 4th waves for qualitative analysis, will be discussed.

  5. Loss of Llgl1 in retinal neuroepithelia reveals links between apical domain size, Notch activity and neurogenesis

    PubMed Central

    Clark, Brian S.; Cui, Shuang; Miesfeld, Joel B.; Klezovitch, Olga; Vasioukhin, Valeri; Link, Brian A.

    2012-01-01

    To gain insights into the cellular mechanisms of neurogenesis, we analyzed retinal neuroepithelia deficient for Llgl1, a protein implicated in apicobasal cell polarity, asymmetric cell division, cell shape and cell cycle exit. We found that vertebrate retinal neuroepithelia deficient for Llgl1 retained overt apicobasal polarity, but had expanded apical domains. Llgl1 retinal progenitors also had increased Notch activity and reduced rates of neurogenesis. Blocking Notch function by depleting Rbpj restored normal neurogenesis. Experimental expansion of the apical domain, through inhibition of Shroom3, also increased Notch activity and reduced neurogenesis. Significantly, in wild-type retina, neurogenic retinal progenitors had smaller apical domains compared with proliferative neuroepithelia. As nuclear position during interkinetic nuclear migration (IKNM) has been previously linked with cell cycle exit, we analyzed this phenomenon in cells depleted of Llgl1. We found that although IKNM was normal, the relationship between nuclear position and neurogenesis was shifted away from the apical surface, consistent with increased pro-proliferative and/or anti-neurogenic signals associated with the apical domain. These data, in conjunction with other findings, suggest that, in retinal neuroepithelia, the size of the apical domain modulates the strength of polarized signals that influence neurogenesis. PMID:22492354

  6. Activation induced deaminase C-terminal domain links DNA breaks to end protection and repair during class switch recombination.

    PubMed

    Zahn, Astrid; Eranki, Anil K; Patenaude, Anne-Marie; Methot, Stephen P; Fifield, Heather; Cortizas, Elena M; Foster, Paul; Imai, Kohsuke; Durandy, Anne; Larijani, Mani; Verdun, Ramiro E; Di Noia, Javier M

    2014-03-18

    Activation-induced deaminase (AID) triggers antibody class switch recombination (CSR) in B cells by initiating DNA double strand breaks that are repaired by nonhomologous end-joining pathways. A role for AID at the repair step is unclear. We show that specific inactivation of the C-terminal AID domain encoded by exon 5 (E5) allows very efficient deamination of the AID target regions but greatly impacts the efficiency and quality of subsequent DNA repair. Specifically eliminating E5 not only precludes CSR but also, causes an atypical, enzymatic activity-dependent dominant-negative effect on CSR. Moreover, the E5 domain is required for the formation of AID-dependent Igh-cMyc chromosomal translocations. DNA breaks at the Igh switch regions induced by AID lacking E5 display defective end joining, failing to recruit DNA damage response factors and undergoing extensive end resection. These defects lead to nonproductive resolutions, such as rearrangements and homologous recombination that can antagonize CSR. Our results can explain the autosomal dominant inheritance of AID variants with truncated E5 in patients with hyper-IgM syndrome 2 and establish that AID, through the E5 domain, provides a link between DNA damage and repair during CSR.

  7. Polyaniline shell cross-linked Fe3O4 magnetic nanoparticles for heat activated killing of cancer cells.

    PubMed

    Rana, Suman; Jadhav, Neena V; Barick, K C; Pandey, B N; Hassan, P A

    2014-08-28

    Superparamagnetic Fe3O4 nanoparticles are appealing materials for heat activated killing of cancer cells. Here, we report a novel method to enhance the heat activated killing of cancer cells under an AC magnetic field (AMF) by introducing a polyaniline impregnated shell onto the surface of Fe3O4 nanoparticles. These polyaniline shell cross-linked magnetic nanoparticles (PSMN) were prepared by in situ polymerization of aniline hydrochloride on the surface of carboxyl PEGylated Fe3O4 nanoparticles. XRD and TEM analyses revealed the formation of single phase inverse spinel Fe3O4 nanoparticles of a size of about 10 nm. The successful growth of the polyaniline shell on the surface of carboxyl PEGylated magnetic nanoparticles (CPMN) is evident from FTIR spectra, DLS, TGA, zeta-potential and magnetic measurements. Both CPMN and PSMN show good colloidal stability, superparamagnetic behavior at room temperature and excellent heating efficacy under AMF. It has been observed that the heating efficacy of PSMN under AMF was slightly reduced as compared to that of CPMN. The enhanced toxicity of PSMN to cancer cells under AMF suggests their strong potential for magnetic hyperthermia. Furthermore, PSMN shows high loading affinity for an anticancer drug (doxorubicin), its sustained release and substantial internalization in tumor cells. PMID:24948377

  8. Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity

    PubMed Central

    Verdeguer, Francisco; Soustek, Meghan S.; Hatting, Maximilian; Blättler, Sharon M.; McDonald, Devin; Barrow, Joeva J.

    2015-01-01

    Mitochondrial oxidative and thermogenic functions in brown and beige adipose tissues modulate rates of energy expenditure. It is unclear, however, how beige or white adipose tissue contributes to brown fat thermogenic function or compensates for partial deficiencies in this tissue and protects against obesity. Here, we show that the transcription factor Yin Yang 1 (YY1) in brown adipose tissue activates the canonical thermogenic and uncoupling gene expression program. In contrast, YY1 represses a series of secreted proteins, including fibroblast growth factor 21 (FGF21), bone morphogenetic protein 8b (BMP8b), growth differentiation factor 15 (GDF15), angiopoietin-like 6 (Angptl6), neuromedin B, and nesfatin, linked to energy expenditure. Despite substantial decreases in mitochondrial thermogenic proteins in brown fat, mice lacking YY1 in this tissue are strongly protected against diet-induced obesity and exhibit increased energy expenditure and oxygen consumption in beige and white fat depots. The increased expression of secreted proteins correlates with elevation of energy expenditure and promotion of beige and white fat activation. These results indicate that YY1 in brown adipose tissue controls antagonistic gene expression programs associated with energy balance and maintenance of body weight. PMID:26503783

  9. Structure of the asparagine-linked sugar chains of porcine kidney and human urine cerebroside sulfate activator protein.

    PubMed

    Faull, K F; Johnson, J; Kim, M J; To, T; Whitelegge, J P; Stevens, R L; Fluharty, C B; Fluharty, A L

    2000-12-01

    The specific sugar residues and their linkages in the oligosaccharides from pig kidney and human urine cerebroside sulfate activator proteins (saposin B), although previously hypothesized, have been unambiguously characterized. Exhaustive sequential exoglycosidase digestion of the trimethyl-p-aminophenyl derivatives, followed by either matrix-assisted laser desorption/ionization and/or mass spectrometry, was used to define the residues and their linkages. The oligosaccharides were enzymatically released from the proteins by treatment with peptidyl-N-glycosidase F and separated from the proteins by reversed-phase high-performance liquid chromatography (HPLC). Reducing termini were converted to the trimethyl-p-aminophenyl derivative and the samples were further purified by normal-phase HPLC. The derivatized carbohydrates were then treated sequentially with a series of exoglycosidases of defined specificity, and the products of each digestion were examined by mass spectrometry. The pentasaccharides from pig kidney and human urine protein were shown to be of the asparagine-linked complex type composed of mannose-alpha 1-6-mannose-beta 1-4-N-acetylglucosamine-N-acetylglucosamine(alpha 1-6-fucose). This highly degraded structure probably represents the final product of intra-lysosomal exoglycosidase digestion. Oligosaccharide sequencing by specific exoglycosidase degradation coupled with mass spectrometry is more rapid than conventional oligosaccharide sequencing. The procedures developed will be useful for sequencing other oligosaccharides including those from other members of the lipid-binding protein class to which cerebroside sulfate activator belongs. (c) 2000 John Wiley & Sons, Ltd.

  10. Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans

    PubMed Central

    Meyer-Lindenberg, A; Kolachana, B; Gold, B; Olsh, A; Nicodemus, KK; Mattay, V; Dean, M; Weinberger, DR

    2009-01-01

    In mammals, the neuropeptide vasopressin is a key molecule for complex emotional and social behaviours. Two microsatellite polymorphisms, RS1 and RS3, near the promoter of AVPR1A, encoding the receptor subtype most heavily implicated in behaviour regulation, have been linked to autism and behavioural traits. However, the impact of these variants on human brain function is unknown. Here we show that human amygdala function is strongly associated with genetic variation in AVPR1A. Using an imaging genetics approach in a sample of 121 volunteers studied with an emotional face-matching paradigm, we found that differential activation of amygdala is observed in carriers of risk alleles for RS3 and RS1. Alleles in RS1 previously reported to be significantly over- and undertransmitted to autistic probands showed opposing effects on amygdala activation. Furthermore, we show functional difference in human brain between short and long repeat lengths that mirror findings recently obtained in a corresponding variant in voles. Our results indicate a neural mechanism mediating genetic risk for autism through an impact on amygdala signalling and provide a rationale for exploring therapeutic strategies aimed at abnormal amygdala function in this disorder. PMID:18490926

  11. Surface roughness-induced speed increase for active Janus micromotors† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5cc01607j 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

    Choudhury, Udit; Soler, Lluís; Gibbs, John G.; Fischer, Peer

    2015-01-01

    We demonstrate a simple physical fabrication method to control surface roughness of Janus micromotors and fabricate self-propelled active Janus microparticles with rough catalytic platinum surfaces that show a four-fold increase in their propulsion speed compared to conventional Janus particles coated with a smooth Pt layer. PMID:25905919

  12. Combination of nifedipine and subtherapeutic dose of cyclosporin additively suppresses mononuclear cells activation of patients with rheumatoid arthritis and normal individuals via Ca2+–calcineurin–nuclear factor of activated T cells pathway

    PubMed Central

    Lai, N-S; Yu, C-L; Yin, W-Y; Yu, H-C; Huang, H-B; Tung, C-H; Lu, M-C

    2012-01-01

    Abnormal Ca2+-mediated signalling contributes to the pathogenesis of rheumatoid arthritis (RA). However, the potential implication of calcium channel blocker in RA remained unknown. We hypothesized that nifedipine, an L-type calcium channel blocker, combined with a calcineurin inhibitor, could suppress T cell activation via targeting different level of the Ca2+ signalling pathway. The percentage of activated T cells and the apoptotic rate of mononuclear cells (MNCs) was measured by flow cytometry. The MNC viability, cytokine production, cytosolic Ca2+ level and activity of the nuclear factor of activated T cells (NFAT) were measured by enzyme-linked immunosorbent assay (ELISA). The NFAT-regulated gene expression, including interleukin (IL)-2, interferon (IFN)-γ and granulocyte–macrophage colony-stimulating factor (GM-CSF), was measured by real-time polymerase chain reaction (PCR). We found that the percentage of activated T cells in anti-CD3 + anti-CD28-activated MNC was higher in RA patients. High doses of nifedipine (50 µM) increased MNCs apoptosis, inhibited T cell activation and decreased T helper type 2 (Th1) (IFN-γ)/Th2 (IL-10) cytokine production in both groups. The Ca2+ influx was lower in anti-CD3 + anti-CD28-activated MNC from RA patients than healthy volunteers and suppressed by nifedipine. When combined with a subtherapeutic dose (50 ng/ml) of cyclosporin, 1 µM nifedipine suppressed the percentage of activated T cells in both groups. Moreover, this combination suppressed more IFN-γ secretion and NFAT-regulated gene (GM-CSF and IFN-γ) expression in RA-MNCs than normal MNCs via decreasing the activity of NFATc1. In conclusion, we found that L-type Ca2+ channel blockers and subtherapeutic doses of cyclosporin act additively to suppress the Ca2+-calcineurin-NFAT signalling pathway, leading to inhibition of T cell activity. We propose that this combination may become a potential treatment of RA. PMID:22385242

  13. Activation of a PGC-1-related coactivator (PRC)-dependent inflammatory stress program linked to apoptosis and premature senescence.

    PubMed

    Gleyzer, Natalie; Scarpulla, Richard C

    2013-03-22

    PGC-1-related coactivator (PRC), a growth-regulated member of the PGC-1 coactivator family, contributes to the expression of the mitochondrial respiratory apparatus. PRC also orchestrates a robust response to metabolic stress by promoting the expression of multiple genes specifying inflammation, proliferation, and metabolic reprogramming. Here, we demonstrate that this PRC-dependent stress program is activated during apoptosis and senescence, two major protective mechanisms against cellular dysfunction. Both PRC and its targets (IL1α, SPRR2D, and SPRR2F) were rapidly induced by menadione, an agent that promotes apoptosis through the generation of intracellular oxidants. Menadione-induced apoptosis and the PRC stress program were blocked by the antioxidant N-acetylcysteine. The PRC stress response was also activated by the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN-38), an inducer of premature senescence in tumor cells. Cells treated with SN-38 displayed morphological characteristics of senescence and express senescence-associated β-galactosidase activity. In contrast to menadione, the SN-38 induction of the PRC program occurred over an extended time course and was antioxidant-insensitive. The potential adaptive function of the PRC stress response was investigated by treating cells with meclizine, a drug that promotes glycolytic energy metabolism and has been linked to cardio- and neuroprotection against ischemia-reperfusion injury. Meclizine increased lactate production and was a potent inducer of the PRC stress program, suggesting that PRC may contribute to the protective effects of meclizine. Finally, c-MYC and PRC were coordinately induced under all conditions tested, implicating c-MYC in the biological response to metabolic stress. The results suggest a general role for PRC in the adaptive response to cellular dysfunction. PMID:23364789

  14. Abnormal Brain Activation in Neurofibromatosis Type 1: A Link between Visual Processing and the Default Mode Network

    PubMed Central

    Violante, Inês R.; Ribeiro, Maria J.; Cunha, Gil; Bernardino, Inês; Duarte, João V.; Ramos, Fabiana; Saraiva, Jorge; Silva, Eduardo; Castelo-Branco, Miguel

    2012-01-01

    Neurofibromatosis type 1 (NF1) is one of the most common single gene disorders affecting the human nervous system with a high incidence of cognitive deficits, particularly visuospatial. Nevertheless, neurophysiological alterations in low-level visual processing that could be relevant to explain the cognitive phenotype are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to study early cortical visual pathways in children and adults with NF1. We employed two distinct stimulus types differing in contrast and spatial and temporal frequencies to evoke relatively different activation of the magnocellular (M) and parvocellular (P) pathways. Hemodynamic responses were investigated in retinotopically-defined regions V1, V2 and V3 and then over the acquired cortical volume. Relative to matched control subjects, patients with NF1 showed deficient activation of the low-level visual cortex to both stimulus types. Importantly, this finding was observed for children and adults with NF1, indicating that low-level visual processing deficits do not ameliorate with age. Moreover, only during M-biased stimulation patients with NF1 failed to deactivate or even activated anterior and posterior midline regions of the default mode network. The observation that the magnocellular visual pathway is impaired in NF1 in early visual processing and is specifically associated with a deficient deactivation of the default mode network may provide a neural explanation for high-order cognitive deficits present in NF1, particularly visuospatial and attentional. A link between magnocellular and default mode network processing may generalize to neuropsychiatric disorders where such deficits have been separately identified. PMID:22723888

  15. Linking the SASSCAL WeatherNet and data management/rescue activities to provide consistent information for climate change assessments in Southern Africa

    NASA Astrophysics Data System (ADS)

    Helmschrot, J.; Kaspar, F.; Muche, G.; Hillmann, T.; Kanyanga, J.; Butale, M.; Nascimento, D.; Josenhans, K.; Falanga, E.; Neto, F. O. S.; Kruger, S.; Juergens, N.

    2014-12-01

    Many countries of Southern Africa face inadequate weather monitoring networks to provide reliable and consistent information for the development of efficient management strategies for sustainable water and land resources management, drought and flood risk analysis and forecasts as well as climate change impacts assessments. In addition, some existing networks are characterized by station data showing notable gaps in long-term observations. On the other hand, useful climate information is saved in historical documents and archives, but only barely explored up to now. Such documents are also available in archives of European meteorological services, partly also not yet in digital format. A main aim of the SASSCAL Initiative (Southern African Science Service Centre for Climate Change and Adaptive Land Management; www.sasscal.org) is to improve the availability of reliable meteorological baseline data along with a set of analytical methods to strengthen the research capacities in the SASSCAL region including Angola, Botswana, Namibia, South Africa and Zambia, and therewith to support and integrate information of existing national monitoring networks of the Southern African region. In close cooperation with the national weather authorities and various research institutions of the SASSCAL region, the above mentioned deficits are specifically addressed by i) extending the existing national monitoring networks through additional automatic weather stations and their integration in the SASSCAL WeatherNet which in near future hosts about 130 stations, ii) contributing to the development of Climate Data Management Systems (CDMS) at the national weather authorities in Angola, Botswana and Zambia and iii) the provision of additional time series of climate data based on the historic documents from various archives in all countries. The paper presents first results and shows how these efforts are linked to provide consistent climate information for Southern Africa in order to

  16. Reduced Ovarian Glyoxalase-I Activity by Dietary Glycotoxins and Androgen Excess: A Causative Link to Polycystic Ovarian Syndrome

    PubMed Central

    Kandaraki, Eleni; Chatzigeorgiou, Antonis; Piperi, Christina; Palioura, Eleni; Palimeri, Sotiria; Korkolopoulou, Penelope; Koutsilieris, Michael; Papavassiliou, Athanasios G

    2012-01-01

    Glyoxalase detoxification system composed of glyoxalase (GLO)-I and GLO-II is ubiquitously expressed and implicated in the protection against cellular damage because of cytotoxic metabolites such as advanced glycation end products (AGEs). Recently, ovarian tissue has emerged as a new target of excessive AGE deposition and has been associated with either a high AGE diet in experimental animals or hyperandrogenic disorders such as polycystic ovarian syndrome (PCOS) in humans. This study was designed to investigate the impact of dietary AGEs and androgens in rat ovarian GLO-I activity of normal nonandrogenized (NAN, group A, n = 18) and androgenized prepubertal (AN) rats (group B, n = 29). Both groups were further randomly assigned, either to a high-AGE (HA) or low-AGE (LA) diet for 3 months. The activity of ovarian GLO-I was significantly reduced in normal NAN animals fed an HA diet compared with an LA diet (p = 0.006). Furthermore, GLO-I activity was markedly reduced in AN animals compared with NAN (p ≤ 0.001) when fed with the corresponding diet type. In addition, ovarian GLO-I activity was positively correlated with the body weight gain (rs = 0.533, p < 0.001), estradiol (rs = 0.326, p = 0.033) and progesterone levels (rs = 0.500, p < 0.001). A negative correlation was observed between GLO-I activity and AGE expression in the ovarian granulosa cell layer of all groups with marginal statistical significance (rs = −0.263, p = 0.07). The present data demonstrate that ovarian GLO-I activity may be regulated by dietary composition and androgen levels. Modification of ovarian GLO-I activity, observed for the first time in this androgenized prepubertal rat model, may present a contributing factor to the reproductive dysfunction characterizing PCOS. PMID:22859292

  17. TRPA1 activation leads to neurogenic vasodilatation: involvement of reactive oxygen nitrogen species in addition to CGRP and NO

    PubMed Central

    Aubdool, Aisah A; Kodji, Xenia; Abdul‐Kader, Nayaab; Heads, Richard; Fernandes, Elizabeth S; Bevan, Stuart

    2016-01-01

    Abstract Background and Purpose Transient receptor potential ankyrin‐1 (TRPA1) activation is known to mediate neurogenic vasodilatation. We investigated the mechanisms involved in TRPA1‐mediated peripheral vasodilatation in vivo using the TRPA1 agonist cinnamaldehyde. Experimental Approach Changes in vascular ear blood flow were measured in anaesthetized mice using laser Doppler flowmetry. Key Results Topical application of cinnamaldehyde to the mouse ear caused a significant increase in blood flow in the skin of anaesthetized wild‐type (WT) mice but not in TRPA1 knockout (KO) mice. Cinnamaldehyde‐induced vasodilatation was inhibited by the pharmacological blockade of the potent microvascular vasodilator neuropeptide CGRP and neuronal NOS‐derived NO pathways. Cinnamaldehyde‐mediated vasodilatation was significantly reduced by treatment with reactive oxygen nitrogen species (RONS) scavenger such as catalase and the SOD mimetic TEMPOL, supporting a role of RONS in the downstream vasodilator TRPA1‐mediated response. Co‐treatment with a non‐selective NOS inhibitor L‐NAME and antioxidant apocynin further inhibited the TRPA1‐mediated vasodilatation. Cinnamaldehyde treatment induced the generation of peroxynitrite that was blocked by the peroxynitrite scavenger FeTPPS and shown to be dependent on TRPA1, as reflected by an increase in protein tyrosine nitration in the skin of WT, but not in TRPA1 KO mice. Conclusion and Implications This study provides in vivo evidence that TRPA1‐induced vasodilatation mediated by cinnamaldehyde requires neuronal NOS‐derived NO, in addition to the traditional neuropeptide component. A novel role of peroxynitrite is revealed, which is generated downstream of TRPA1 activation by cinnamaldehyde. This mechanistic pathway underlying TRPA1‐mediated vasodilatation may be important in understanding the role of TRPA1 in pathophysiological situations. PMID:27189253

  18. Influence of fat addition on the antimicrobial activity of sodium lactate, lauric arginate and methylparaben in minced meat.

    PubMed

    Magrinyà, Núria; Terjung, Nino; Loeffler, Myriam; Gibis, Monika; Bou, Ricard; Weiss, Jochen

    2015-12-23

    A minced meat model system containing three different fat levels (0, 15, and 50 wt.%) was used to evaluate the antimicrobial efficacy of three antimicrobials with different aqueous solubilities (sodium lactate>lauric arginate (Nα-lauroyl-L-arginine ethyl ester, LAE)>methylparaben). Various concentrations of sodium lactate (20, 40, and 60 mg/g), lauric arginate (0.5, 1, 1.5, 2.0, and 2.5 mg/g) and methylparaben (0.1, 0.5, 1.0, and 2.0 mg/g) were used to evaluate the antimicrobial activity against natural meat microbiota (total aerobic mesophilic colony counts, coliform bacteria, and lactic acid bacteria). The results indicate that the three antimicrobials tested are influenced at different strengths by the changes of the fat addition of the minced meat. The antimicrobial efficacy of LAE and methylparaben is increased by a higher fat content in the meat batter, whereas for lactate no clear lactate proportionality relationship can be seen. This structure sensitivity is most strongly pronounced with lauric arginate, which we attributed to the amphiphilic character of the molecule.

  19. Cationic additives in nanosystems activate cytotoxicity and inflammatory response of human neutrophils: lipid nanoparticles versus polymeric nanoparticles

    PubMed Central

    Hwang, Tsong-Long; Aljuffali, Ibrahim A; Lin, Chwan-Fwu; Chang, Yuan-Ting; Fang, Jia-You

    2015-01-01

    This report compares the effect of lipid and polymeric nanoparticles upon human neutrophils in the presence of cationic surfactants. Nanostructured lipid carriers and poly(lactic-co-glycolic) acid nanoparticles were manufactured as lipid and polymeric systems, respectively. Some cytotoxic and proinflammatory mediators such as lactate dehydrogenase (LDH), elastase, O2•−, and intracellular Ca2+ were examined. The nanoparticles showed a size of 170–225 nm. Incorporation of cetyltrimethylammonium bromide or soyaethyl morpholinium ethosulfate, the cationic surfactant, converted zeta potential from a negative to a positive charge. Nanoparticles without cationic surfactants revealed a negligible change on immune and inflammatory responses. Cationic surfactants in both nanoparticulate and free forms induced cell death and the release of mediators. Lipid nanoparticles generally demonstrated a greater response compared to polymeric nanoparticles. The neutrophil morphology observed by electron microscopy confirmed this trend. Cetyltrimethylammonium bromide as the coating material showed more significant activation of neutrophils than soyaethyl morpholinium ethosulfate. Confocal microscope imaging displayed a limited internalization of nanoparticles into neutrophils. It is proposed that cationic nanoparticles interact with the cell membrane, triggering membrane disruption and the following Ca2+ influx. The elevation of intracellular Ca2+ induces degranulation and oxidative stress. The consequence of these effects is cytotoxicity and cell death. Caution should be taken when selecting feasible nanoparticulate formulations and cationic additives for consideration of applicability and toxicity. PMID:25609950

  20. Radioactively contaminated electric arc furnace dust as an addition to the immobilization mortar in low- and medium-activity repositories.

    PubMed

    Castellote, Marta; Menéndez, Esperanza; Andrade, Carmen; Zuloaga, Pablo; Navarro, Mariano; Ordóñez, Manuel

    2004-05-15

    Electric arc furnace dust (EAFD), generated by the steel-making industry, is in itself an intrinsic hazardous waste; however, the case may also be that scrap used in the process is accidentally contaminated by radioactive elements such as cesium. In this case the resulting EAFD is to be handled as radioactive waste, being duly confined in low- and medium-activity repositories (LMAR). What this paper studies is the reliability of using this radioactive EAFD as an addition in the immobilization mortar of the containers of the LMAR, that is, from the point of view of the durability. Different mixes of mortar containing different percentages of EAFD have been subjected to flexural and compressive strength, initial and final setting time, XRD study, total porosity and pore size distribution, determination of the chloride diffusion coefficient, dimensional stability tests, hydration heat, workability of the fresh mix, and leaching behavior. What is deduced from the results is that for the conditions used in this research, (cement + sand) can be replaced by EAFD upto a ratio [EAFD/(cement + EAFD)] of 46% in the immobilization mortar of LMAR, apparently without any loss in the long-term durability properties of the mortar.

  1. Synthesis of Highly Active Mg-BASED Hydrides Using Hydriding Combustion Synthesis and NbF5 Additives

    NASA Astrophysics Data System (ADS)

    Chourashiya, M. G.; Park, C. N.; Park, C. J.

    2012-09-01

    Superiority of the hydriding combustion (HC) technique over conventional metallurgical approach to the synthesis of cost-effective Mg based hydrides, which show promise as hydrogen storage materials, is well known. In the present research, we report further improvements in HC prepared Mg-based materials, achieved by optimizing the preparative parameters of HC and by catalytic addition. Mg90-Ni60-C40 composites prepared using optimized processing parameters were ball-milled with NbF5 (10 h) and characterized for their micro-structural and hydriding properties. The ball-milled/catalyzed powder showed decreased crystallinity with CNTs on its surfaces. Surface area of the ball-milled powder decreased to almost half of the as-HC powder, while TG analysis revealed a four-fold decrease in the desorption temperature of the milled powder compared to that of the as-HC prepared powder. Activated samples achieved the maximum absorption/desorption limits (5.3 wt.%) at as low as 100°C, underlining the possibility of the use of these materials in portable hydrogen storage devices.

  2. Influence of fat addition on the antimicrobial activity of sodium lactate, lauric arginate and methylparaben in minced meat.

    PubMed

    Magrinyà, Núria; Terjung, Nino; Loeffler, Myriam; Gibis, Monika; Bou, Ricard; Weiss, Jochen

    2015-12-23

    A minced meat model system containing three different fat levels (0, 15, and 50 wt.%) was used to evaluate the antimicrobial efficacy of three antimicrobials with different aqueous solubilities (sodium lactate>lauric arginate (Nα-lauroyl-L-arginine ethyl ester, LAE)>methylparaben). Various concentrations of sodium lactate (20, 40, and 60 mg/g), lauric arginate (0.5, 1, 1.5, 2.0, and 2.5 mg/g) and methylparaben (0.1, 0.5, 1.0, and 2.0 mg/g) were used to evaluate the antimicrobial activity against natural meat microbiota (total aerobic mesophilic colony counts, coliform bacteria, and lactic acid bacteria). The results indicate that the three antimicrobials tested are influenced at different strengths by the changes of the fat addition of the minced meat. The antimicrobial efficacy of LAE and methylparaben is increased by a higher fat content in the meat batter, whereas for lactate no clear lactate proportionality relationship can be seen. This structure sensitivity is most strongly pronounced with lauric arginate, which we attributed to the amphiphilic character of the molecule. PMID:26344644

  3. Murine elongation factor 1 alpha (EF-1 alpha) is posttranslationally modified by novel amide-linked ethanolamine-phosphoglycerol moieties. Addition of ethanolamine-phosphoglycerol to specific glutamic acid residues on EF-1 alpha

    SciTech Connect

    Whiteheart, S.W.; Shenbagamurthi, P.; Chen, L.; Cotter, R.J.; Hart, G.W. )

    1989-08-25

    Elongation Factor 1 alpha (EF-1 alpha), an important eukaryotic translation factor, transports charged aminoacyl-tRNA from the cytosol to the ribosomes during poly-peptide synthesis. Metabolic radiolabeling with ({sup 3}H) ethanolamine shows that, in all cells examined, EF-1 alpha is the major radiolabeled protein. Radiolabeled EF-1 alpha has an apparent Mr = 53,000 and a basic isoelectric point. It is cytosolic and does not contain N-linked oligosaccharides. Trypsin digestion of murine EF-1 alpha generated two major ({sup 3}H)ethanolamine-labeled peptides. Three peptides were sequenced and were identical to two distinct regions of the human EF-1 alpha protein. Blank sequencing cycles coinciding with glutamic acid in the human cDNA-derived sequence were also found to release ({sup 3}H)ethanolamine, and compositional analysis of these peptides confirmed the presence of glutamic acid. Dansylation analysis demonstrates that the amine group of the ethanolamine is blocked. These results indicate that EF-1 alpha is posttranslationally modified by the covalent attachment of ethanolamine via an amide bond to at least two specific glutamic acid residues (Glu-301 and Glu-374). The hydroxyl group of the attached ethanolamine was shown by mass spectrometry and compositional analysis, to be further modified by the addition of a phosphoglycerol unit. This novel posttranslational modification may represent an important alteration of EF-1 alpha, comparable to the regulatory effects of posttranslational methylation of EF-1 alpha lysine residues.

  4. Wear evaluation of a cross-linked medical grade polyethylene by ultra thin layer activation compared to gravimetry

    NASA Astrophysics Data System (ADS)

    Stroosnijder, Marinus F.; Hoffmann, Michael; Sauvage, Thierry; Blondiaux, Gilbert; Vincent, Laetitia

    2005-01-01

    Most of today's artificial joints rely on an articulating couple consisting of a CoCrMo alloy and a medical grade polyethylene. The wear of the polyethylene component is the major cause for long-term failure of these prostheses since the wear debris leads to adverse biological reactions. The polyethylene wear is usually measured by gravimetric methods, which are limited due to a low sensitivity and accuracy. To demonstrate the reliability of ultra thin layer activation (UTLA) as an alternative technique, wear tests on a cross-linked ultra-high-molecular weight polyethylene (XLPE) sliding against CoCrMo were performed on a wear tester featuring multi-directional sliding motion. The amount of polyethylene wear was evaluated by both UTLA and gravimetry. The particular TLA method used in this work employed the implantation of 7Be radioactive recoils into the polyethylene surface by means of a light mass particle beam. The results indicate that apart from its relatively high sensitivity, UTLA also offers the possibility for on-line measurements of polyethylene wear. This makes it a viable and complementary technique in wear test studies for medical implant purposes especially for those involving wear resistant materials and for rapid wear screening.

  5. Reduced Frontoparietal Activity in Schizophrenia Is Linked to a Specific Deficit in Goal Maintenance: A Multisite Functional Imaging Study.

    PubMed

    Poppe, Andrew B; Barch, Deanna M; Carter, Cameron S; Gold, James M; Ragland, John Daniel; Silverstein, Steven M; MacDonald, Angus W

    2016-09-01

    Patients with schizophrenia (SZ) previously demonstrated specific deficits in an executive function known as goal maintenance, associated with reduced middle frontal gyrus (MFG) activity. This study aimed to validate a new tool-the Dot Pattern Expectancy (DPX) task-developed to facilitate multisite imaging studies of goal maintenance deficits in SZ or other disorders. Additionally, it sought to arrive at recommendations for scan length for future studies using the DPX. Forty-seven SZ and 56 healthy controls (HC) performed the DPX in 3-Tesla functional magnetic resonance imaging (fMRI) scanners at 5 sites. Group differences in DPX-related activity were examined with whole brain voxelwise analyses. SZs showed the hypothesized specific performance deficits with as little as 1 block of data. Reduced activity in SZ compared with HC was observed in bilateral frontal pole/MFG, as well as left posterior parietal lobe. Efficiency analyses found significant group differences in activity using 18 minutes of scan data but not 12 minutes. Several behavioral and imaging findings from the goal maintenance literature were robustly replicated despite the use of different scanners at different sites. We did not replicate a previous correlation with disorganization symptoms among patients. Results were consistent with an executive/attention network dysfunction in the higher levels of a cascading executive system responsible for goal maintenance. Finally, efficiency analyses found that 18 minutes of scanning during the DPX task is sufficient to detect group differences with a similar sample size.

  6. Redox-active porous coordination polymers prepared by trinuclear heterometallic pivalate linking with the redox-active nickel(II) complex: synthesis, structure, magnetic and redox properties, and electrocatalytic activity in organic compound dehalogenation in heterogeneous medium.

    PubMed

    Lytvynenko, A S; Kolotilov, S V; Kiskin, M A; Cador, O; Golhen, S; Aleksandrov, G G; Mishura, A M; Titov, V E; Ouahab, L; Eremenko, I L; Novotortsev, V M

    2014-05-19

    Linking of the trinuclear pivalate fragment Fe2CoO(Piv)6 by the redox-active bridge Ni(L)2 (compound 1; LH is Schiff base from hydrazide of 4-pyridinecarboxylic acid and 2-pyridinecarbaldehyde, Piv(-) = pivalate) led to formation of a new porous coordination polymer (PCP) {Fe2CoO(Piv)6}{Ni(L)2}1.5 (2). X-ray structures of 1 and 2 were determined. A crystal lattice of compound 2 is built from stacked 2D layers; the Ni(L)2 units can be considered as bridges, which bind two Fe2CoO(Piv)6 units. In desolvated form, 2 possesses a porous crystal lattice (SBET = 50 m(2) g(-1), VDR = 0.017 cm(3) g(-1) estimated from N2 sorption at 78 K). At 298 K, 2 absorbed a significant quantity of methanol (up to 0.3 cm(3) g(-1)) and chloroform. Temperature dependence of molar magnetic susceptibility of 2 could be fitted as superposition of χMT of Fe2CoO(Piv)6 and Ni(L)2 units, possible interactions between them were taken into account using molecular field model. In turn, magnetic properties of the Fe2CoO(Piv)6 unit were fitted using two models, one of which directly took into account a spin-orbit coupling of Co(II), and in the second model the spin-orbit coupling of Co(II) was approximated as zero-field splitting. Electrochemical and electrocatalytic properties of 2 were studied by cyclic voltammetry in suspension and compared with electrochemical and electrocatalytic properties of a soluble analogue 1. A catalytic effect was determined by analysis of the catalytic current dependency on concentrations of the substrate. Compound 1 possessed electrocatalytic activity in organic halide dehalogenation, and such activity was preserved for the Ni(L)2 units, incorporated into the framework of 2. In addition, a new property occurred in the case of 2: the catalytic activity of PCP depended on its sorption capacity with respect to the substrate. In contrast to homogeneous catalysts, usage of solid PCPs may allow selectivity due to porous structure and simplify separation of product. PMID

  7. Changes in O-Linked N-Acetylglucosamine (O-GlcNAc) Homeostasis Activate the p53 Pathway in Ovarian Cancer Cells.

    PubMed

    de Queiroz, Rafaela Muniz; Madan, Rashna; Chien, Jeremy; Dias, Wagner Barbosa; Slawson, Chad

    2016-09-01

    O-GlcNAcylation is a dynamic post-translational modification consisting of the addition of a single N-acetylglucosamine sugar to serine and threonine residues in proteins by the enzyme O-linked β-N-acetylglucosamine transferase (OGT), whereas the enzyme O-GlcNAcase (OGA) removes the modification. In cancer, tumor samples present with altered O-GlcNAcylation; however, changes in O-GlcNAcylation are not consistent between tumor types. Interestingly, the tumor suppressor p53 is modified by O-GlcNAc, and most solid tumors contain mutations in p53 leading to the loss of p53 function. Because ovarian cancer has a high frequency of p53 mutation rates, we decided to investigate the relationship between O-GlcNAcylation and p53 function in ovarian cancer. We measured a significant decrease in O-GlcNAcylation of tumor tissue in an ovarian tumor microarray. Furthermore, O-GlcNAcylation was increased, and OGA protein and mRNA levels were decreased in ovarian tumor cell lines not expressing the protein p53. Treatment with the OGA inhibitor Thiamet-G (TMG), silencing of OGA, or overexpression of OGA and OGT led to p53 stabilization, increased nuclear localization, and increased protein and mRNA levels of p53 target genes. These data suggest that changes in O-GlcNAc homeostasis activate the p53 pathway. Combination treatment of the chemotherapeutic cisplatin with TMG decreased tumor cell growth and enhanced cell cycle arrest without impairing cytotoxicity. The effects of TMG on tumor cell growth were partially dependent on wild type p53 activation. In conclusion, changes in O-GlcNAc homeostasis activate the wild type p53 pathway in ovarian cancer cells, and OGA inhibition has the potential as an adjuvant treatment for ovarian carcinoma. PMID:27402830

  8. Changes in O-Linked N-Acetylglucosamine (O-GlcNAc) Homeostasis Activate the p53 Pathway in Ovarian Cancer Cells.

    PubMed

    de Queiroz, Rafaela Muniz; Madan, Rashna; Chien, Jeremy; Dias, Wagner Barbosa; Slawson, Chad

    2016-09-01

    O-GlcNAcylation is a dynamic post-translational modification consisting of the addition of a single N-acetylglucosamine sugar to serine and threonine residues in proteins by the enzyme O-linked β-N-acetylglucosamine transferase (OGT), whereas the enzyme O-GlcNAcase (OGA) removes the modification. In cancer, tumor samples present with altered O-GlcNAcylation; however, changes in O-GlcNAcylation are not consistent between tumor types. Interestingly, the tumor suppressor p53 is modified by O-GlcNAc, and most solid tumors contain mutations in p53 leading to the loss of p53 function. Because ovarian cancer has a high frequency of p53 mutation rates, we decided to investigate the relationship between O-GlcNAcylation and p53 function in ovarian cancer. We measured a significant decrease in O-GlcNAcylation of tumor tissue in an ovarian tumor microarray. Furthermore, O-GlcNAcylation was increased, and OGA protein and mRNA levels were decreased in ovarian tumor cell lines not expressing the protein p53. Treatment with the OGA inhibitor Thiamet-G (TMG), silencing of OGA, or overexpression of OGA and OGT led to p53 stabilization, increased nuclear localization, and increased protein and mRNA levels of p53 target genes. These data suggest that changes in O-GlcNAc homeostasis activate the p53 pathway. Combination treatment of the chemotherapeutic cisplatin with TMG decreased tumor cell growth and enhanced cell cycle arrest without impairing cytotoxicity. The effects of TMG on tumor cell growth were partially dependent on wild type p53 activation. In conclusion, changes in O-GlcNAc homeostasis activate the wild type p53 pathway in ovarian cancer cells, and OGA inhibition has the potential as an adjuvant treatment for ovarian carcinoma.

  9. Modeling external carbon addition in biological nutrient removal processes with an extension of the international water association activated sludge model.

    PubMed

    Swinarski, M; Makinia, J; Stensel, H D; Czerwionka, K; Drewnowski, J

    2012-08-01

    The aim of this study was to expand the International Water Association Activated Sludge Model No. 2d (ASM2d) to account for a newly defined readily biodegradable substrate that can be consumed by polyphosphate-accumulating organisms (PAOs) under anoxic and aerobic conditions, but not under anaerobic conditions. The model change was to add a new substrate component and process terms for its use by PAOs and other heterotrophic bacteria under anoxic and aerobic conditions. The Gdansk (Poland) wastewater treatment plant (WWTP), which has a modified University of Cape Town (MUCT) process for nutrient removal, provided field data and mixed liquor for batch tests for model evaluation. The original ASM2d was first calibrated under dynamic conditions with the results of batch tests with settled wastewater and mixed liquor, in which nitrate-uptake rates, phosphorus-release rates, and anoxic phosphorus uptake rates were followed. Model validation was conducted with data from a 96-hour measurement campaign in the full-scale WWTP. The results of similar batch tests with ethanol and fusel oil as the external carbon sources were used to adjust kinetic and stoichiometric coefficients in the expanded ASM2d. Both models were compared based on their predictions of the effect of adding supplemental carbon to the anoxic zone of an MUCT process. In comparison with the ASM2d, the new model better predicted the anoxic behaviors of carbonaceous oxygen demand, nitrate-nitrogen (NO3-N), and phosphorous (PO4-P) in batch experiments with ethanol and fusel oil. However, when simulating ethanol addition to the anoxic zone of a full-scale biological nutrient removal facility, both models predicted similar effluent NO3-N concentrations (6.6 to 6.9 g N/m3). For the particular application, effective enhanced biological phosphorus removal was predicted by both models with external carbon addition but, for the new model, the effluent PO4-P concentration was approximately one-half of that found from

  10. Use of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms.

    PubMed

    Colgan, Stephen T; Zelesky, Todd C; Chen, Raymond; Likar, Michael D; MacDonald, Bruce C; Hawkins, Joel M; Carroll, Sophia C; Johnson, Gail M; Space, J Sean; Jensen, James F; DeMatteo, Vincent A

    2016-07-01

    Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and cross-linking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin cross-linking were subjected to accelerated stability challenges in the presence and absence of activated carbon. The effects of time and storage conditions were determined. For all of the products studied, activated carbon attenuated drug degradation or gelatin cross-linking. This novel use of activated carbon in pharmaceutical packaging may be useful for enhancing the chemical stability of drug products or the dissolution stability of gelatin-containing dosage forms and may allow for the 1) extension of a drug product's shelf-life when the limiting attribute is