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Sample records for sustained signaling ii

  1. Sustainability of the Benefits Derived from Fadama II Critical ...

    African Journals Online (AJOL)

    ... sustained by the beneficiaries. Future projects should improve on the involvement of beneficiaries in procuring service providers in addition to been exposed to capacity building workshops on asset maintenance to enhance their sustainability. Keywords: Eriti watershed, Fadama II, Sustainable ecosystem management.

  2. Forgetting in Reinforcement Learning Links Sustained Dopamine Signals to Motivation.

    Science.gov (United States)

    Kato, Ayaka; Morita, Kenji

    2016-10-01

    It has been suggested that dopamine (DA) represents reward-prediction-error (RPE) defined in reinforcement learning and therefore DA responds to unpredicted but not predicted reward. However, recent studies have found DA response sustained towards predictable reward in tasks involving self-paced behavior, and suggested that this response represents a motivational signal. We have previously shown that RPE can sustain if there is decay/forgetting of learned-values, which can be implemented as decay of synaptic strengths storing learned-values. This account, however, did not explain the suggested link between tonic/sustained DA and motivation. In the present work, we explored the motivational effects of the value-decay in self-paced approach behavior, modeled as a series of 'Go' or 'No-Go' selections towards a goal. Through simulations, we found that the value-decay can enhance motivation, specifically, facilitate fast goal-reaching, albeit counterintuitively. Mathematical analyses revealed that underlying potential mechanisms are twofold: (1) decay-induced sustained RPE creates a gradient of 'Go' values towards a goal, and (2) value-contrasts between 'Go' and 'No-Go' are generated because while chosen values are continually updated, unchosen values simply decay. Our model provides potential explanations for the key experimental findings that suggest DA's roles in motivation: (i) slowdown of behavior by post-training blockade of DA signaling, (ii) observations that DA blockade severely impairs effortful actions to obtain rewards while largely sparing seeking of easily obtainable rewards, and (iii) relationships between the reward amount, the level of motivation reflected in the speed of behavior, and the average level of DA. These results indicate that reinforcement learning with value-decay, or forgetting, provides a parsimonious mechanistic account for the DA's roles in value-learning and motivation. Our results also suggest that when biological systems for value

  3. Forgetting in Reinforcement Learning Links Sustained Dopamine Signals to Motivation.

    Directory of Open Access Journals (Sweden)

    Ayaka Kato

    2016-10-01

    Full Text Available It has been suggested that dopamine (DA represents reward-prediction-error (RPE defined in reinforcement learning and therefore DA responds to unpredicted but not predicted reward. However, recent studies have found DA response sustained towards predictable reward in tasks involving self-paced behavior, and suggested that this response represents a motivational signal. We have previously shown that RPE can sustain if there is decay/forgetting of learned-values, which can be implemented as decay of synaptic strengths storing learned-values. This account, however, did not explain the suggested link between tonic/sustained DA and motivation. In the present work, we explored the motivational effects of the value-decay in self-paced approach behavior, modeled as a series of 'Go' or 'No-Go' selections towards a goal. Through simulations, we found that the value-decay can enhance motivation, specifically, facilitate fast goal-reaching, albeit counterintuitively. Mathematical analyses revealed that underlying potential mechanisms are twofold: (1 decay-induced sustained RPE creates a gradient of 'Go' values towards a goal, and (2 value-contrasts between 'Go' and 'No-Go' are generated because while chosen values are continually updated, unchosen values simply decay. Our model provides potential explanations for the key experimental findings that suggest DA's roles in motivation: (i slowdown of behavior by post-training blockade of DA signaling, (ii observations that DA blockade severely impairs effortful actions to obtain rewards while largely sparing seeking of easily obtainable rewards, and (iii relationships between the reward amount, the level of motivation reflected in the speed of behavior, and the average level of DA. These results indicate that reinforcement learning with value-decay, or forgetting, provides a parsimonious mechanistic account for the DA's roles in value-learning and motivation. Our results also suggest that when biological systems

  4. The Relationship Between Acoustic Signal Typing and Perceptual Evaluation of Tracheoesophageal Voice Quality for Sustained Vowels.

    Science.gov (United States)

    Clapham, Renee P; van As-Brooks, Corina J; van Son, Rob J J H; Hilgers, Frans J M; van den Brekel, Michiel W M

    2015-07-01

    To investigate the relationship between acoustic signal typing and perceptual evaluation of sustained vowels produced by tracheoesophageal (TE) speakers and the use of signal typing in the clinical setting. Two evaluators independently categorized 1.75-second segments of narrow-band spectrograms according to acoustic signal typing and independently evaluated the recording of the same segments on a visual analog scale according to overall perceptual acoustic voice quality. The relationship between acoustic signal typing and overall voice quality (as a continuous scale and as a four-point ordinal scale) was investigated and the proportion of inter-rater agreement as well as the reliability between the two measures is reported. The agreement between signal type (I-IV) and ordinal voice quality (four-point scale) was low but significant, and there was a significant linear relationship between the variables. Signal type correctly predicted less than half of the voice quality data. There was a significant main effect of signal type on continuous voice quality scores with significant differences in median quality scores between signal types I-IV, I-III, and I-II. Signal typing can be used as an adjunct to perceptual and acoustic evaluation of the same stimuli for TE speech as part of a multidimensional evaluation protocol. Signal typing in its current form provides limited predictive information on voice quality, and there is significant overlap between signal types II and III and perceptual categories. Future work should consider whether the current four signal types could be refined. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  5. Hunger neurons drive feeding through a sustained, positive reinforcement signal.

    Science.gov (United States)

    Chen, Yiming; Lin, Yen-Chu; Zimmerman, Christopher A; Essner, Rachel A; Knight, Zachary A

    2016-08-24

    The neural mechanisms underlying hunger are poorly understood. AgRP neurons are activated by energy deficit and promote voracious food consumption, suggesting these cells may supply the fundamental hunger drive that motivates feeding. However recent in vivo recording experiments revealed that AgRP neurons are inhibited within seconds by the sensory detection of food, raising the question of how these cells can promote feeding at all. Here we resolve this paradox by showing that brief optogenetic stimulation of AgRP neurons before food availability promotes intense appetitive and consummatory behaviors that persist for tens of minutes in the absence of continued AgRP neuron activation. We show that these sustained behavioral responses are mediated by a long-lasting potentiation of the rewarding properties of food and that AgRP neuron activity is positively reinforcing. These findings reveal that hunger neurons drive feeding by transmitting a positive valence signal that triggers a stable transition between behavioral states.

  6. Detecting Parkinson's disease from sustained phonation and speech signals.

    Directory of Open Access Journals (Sweden)

    Evaldas Vaiciukynas

    Full Text Available This study investigates signals from sustained phonation and text-dependent speech modalities for Parkinson's disease screening. Phonation corresponds to the vowel /a/ voicing task and speech to the pronunciation of a short sentence in Lithuanian language. Signals were recorded through two channels simultaneously, namely, acoustic cardioid (AC and smart phone (SP microphones. Additional modalities were obtained by splitting speech recording into voiced and unvoiced parts. Information in each modality is summarized by 18 well-known audio feature sets. Random forest (RF is used as a machine learning algorithm, both for individual feature sets and for decision-level fusion. Detection performance is measured by the out-of-bag equal error rate (EER and the cost of log-likelihood-ratio. Essentia audio feature set was the best using the AC speech modality and YAAFE audio feature set was the best using the SP unvoiced modality, achieving EER of 20.30% and 25.57%, respectively. Fusion of all feature sets and modalities resulted in EER of 19.27% for the AC and 23.00% for the SP channel. Non-linear projection of a RF-based proximity matrix into the 2D space enriched medical decision support by visualization.

  7. The signal peptidase II (lsp) gene of Bacillus subtilis

    NARCIS (Netherlands)

    Pragai, Z; Tjalsma, H; Bolhuis, A; vanDijl, JM; Venema, G; Bron, S

    The gene encoding the type II signal peptidase (SPase III) of Bacillus subtilis was isolated by screening a genomic DNA library of this bacterium for the ability of increase the levels of globomycin resistance in Escherichia coli, and to complement the growth deficiency at the non-permissive

  8. Hunger neurons drive feeding through a sustained, positive reinforcement signal

    Science.gov (United States)

    Chen, Yiming; Lin, Yen-Chu; Zimmerman, Christopher A; Essner, Rachel A; Knight, Zachary A

    2016-01-01

    The neural mechanisms underlying hunger are poorly understood. AgRP neurons are activated by energy deficit and promote voracious food consumption, suggesting these cells may supply the fundamental hunger drive that motivates feeding. However recent in vivo recording experiments revealed that AgRP neurons are inhibited within seconds by the sensory detection of food, raising the question of how these cells can promote feeding at all. Here we resolve this paradox by showing that brief optogenetic stimulation of AgRP neurons before food availability promotes intense appetitive and consummatory behaviors that persist for tens of minutes in the absence of continued AgRP neuron activation. We show that these sustained behavioral responses are mediated by a long-lasting potentiation of the rewarding properties of food and that AgRP neuron activity is positively reinforcing. These findings reveal that hunger neurons drive feeding by transmitting a positive valence signal that triggers a stable transition between behavioral states. DOI: http://dx.doi.org/10.7554/eLife.18640.001 PMID:27554486

  9. Sustained exposure to catecholamines affects cAMP/PKA compartmentalised signalling in adult rat ventricular myocytes.

    Science.gov (United States)

    Fields, Laura A; Koschinski, Andreas; Zaccolo, Manuela

    2016-07-01

    In the heart compartmentalisation of cAMP/protein kinase A (PKA) signalling is necessary to achieve a specific functional outcome in response to different hormonal stimuli. Chronic exposure to catecholamines is known to be detrimental to the heart and disrupted compartmentalisation of cAMP signalling has been associated to heart disease. However, in most cases it remains unclear whether altered local cAMP signalling is an adaptive response, a consequence of the disease or whether it contributes to the pathogenetic process. We have previously demonstrated that isoforms of PKA expressed in cardiac myocytes, PKA-I and PKA-II, localise to different subcellular compartments and are selectively activated by spatially confined pools of cAMP, resulting in phosphorylation of distinct downstream targets. Here we investigate cAMP signalling in an in vitro model of hypertrophy in primary adult rat ventricular myocytes. By using a real time imaging approach and targeted reporters we find that that sustained exposure to catecholamines can directly affect cAMP/PKA compartmentalisation. This appears to involve a complex mechanism including both changes in the subcellular localisation of individual phosphodiesterase (PDE) isoforms as well as the relocalisation of PKA isoforms. As a result, the preferential coupling of PKA subsets with different PDEs is altered resulting in a significant difference in the level of cAMP the kinase is exposed to, with potential impact on phosphorylation of downstream targets. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  10. TOPAZ II Signal Characterization Measurements Performed at TSET

    Science.gov (United States)

    Wyant, Francis J.; Taylor, James; Frisch, Carl; Logothetis, John

    1994-07-01

    The Russian TOPAZ II Space Nuclear Power System, designated as V-71, has recently been tested on the BAIKAL electric-heater test stand at the Thermionic System Evaluation Test (TSET) facility in Albuquerque, NM. During these tests, members of the Nuclear Electric Propulsion Space Test Program (NEPSTP) team took advantage of the opportunity afforded by these operations to make measurements in order to characterize the noise levels and attributes in support of a possible flight experiment. The measurements taken were related to electrical ``noise'' on the TOPAZ II sensor lines. The purpose was to characterize any noise during TOPAZ II operation in order to verify the accuracy of measured data and evaluate the significance of signal interference associated with the noise.

  11. A postsynaptic PI3K-cII dependent signaling controller for presynaptic homeostatic plasticity

    Science.gov (United States)

    Hauswirth, Anna G; Ford, Kevin J; Wang, Tingting; Fetter, Richard D; Tong, Amy

    2018-01-01

    Presynaptic homeostatic plasticity stabilizes information transfer at synaptic connections in organisms ranging from insect to human. By analogy with principles of engineering and control theory, the molecular implementation of PHP is thought to require postsynaptic signaling modules that encode homeostatic sensors, a set point, and a controller that regulates transsynaptic negative feedback. The molecular basis for these postsynaptic, homeostatic signaling elements remains unknown. Here, an electrophysiology-based screen of the Drosophila kinome and phosphatome defines a postsynaptic signaling platform that includes a required function for PI3K-cII, PI3K-cIII and the small GTPase Rab11 during the rapid and sustained expression of PHP. We present evidence that PI3K-cII localizes to Golgi-derived, clathrin-positive vesicles and is necessary to generate an endosomal pool of PI(3)P that recruits Rab11 to recycling endosomal membranes. A morphologically distinct subdivision of this platform concentrates postsynaptically where we propose it functions as a homeostatic controller for retrograde, trans-synaptic signaling. PMID:29303480

  12. Effects of social sustainability signals on neural valuation signals and taste-experience of food products

    Directory of Open Access Journals (Sweden)

    Laura eEnax

    2015-09-01

    Full Text Available Value-based decision making occurs when individuals choose between different alternatives and place a value on each alternative and its attributes. Marketing actions frequently manipulate product attributes, by adding e.g., health claims on the packaging. A previous imaging study found that an emblem for organic products increased willingness to pay (WTP and activity in the ventral striatum (VS. The current study investigated neural and behavioral processes underlying the influence of Fair Trade (FT labeling on food valuation and choice. Sustainability is an important product attribute for many consumers, with FT signals being one way to highlight ethically sustainable production. Forty participants valuated products in combination with an FT emblem or no emblem and stated their WTP in a bidding task while in an MRI scanner. After that, participants tasted – objectively identical – chocolates, presented either as FT or as conventionally produced. In the fMRI task, WTP was significantly higher for FT products. FT labeling increased activity in regions important for reward-processing and salience, that is, in the VS, anterior and posterior cingulate, as well as superior frontal gyrus. Subjective value, that is, WTP was correlated with activity in the ventromedial prefrontal cortex (vmPFC. We find that the anterior cingulate, VS and superior frontal gyrus exhibit task-related increases in functional connectivity to the vmPFC when an FT product was evaluated, suggesting a network which alters valuation processes. We also found a significant taste-placebo effect, with higher experienced taste pleasantness and intensity for FT labeled chocolates. Our results reveal a possible neural mechanism underlying valuation processes of certified food products. The results are important in light of understanding current marketing trends as well as designing future interventions that aim at positively influencing food choice.

  13. Effects of social sustainability signaling on neural valuation signals and taste-experience of food products.

    Science.gov (United States)

    Enax, Laura; Krapp, Vanessa; Piehl, Alexandra; Weber, Bernd

    2015-01-01

    Value-based decision making occurs when individuals choose between different alternatives and place a value on each alternative and its attributes. Marketing actions frequently manipulate product attributes, by adding, e.g., health claims on the packaging. A previous imaging study found that an emblem for organic products increased willingness to pay (WTP) and activity in the ventral striatum (VS). The current study investigated neural and behavioral processes underlying the influence of Fair Trade (FT) labeling on food valuation and choice. Sustainability is an important product attribute for many consumers, with FT signals being one way to highlight ethically sustainable production. Forty participants valuated products in combination with an FT emblem or no emblem and stated their WTP in a bidding task while in an MRI scanner. After that, participants tasted-objectively identical-chocolates, presented either as "FT" or as "conventionally produced". In the fMRI task, WTP was significantly higher for FT products. FT labeling increased activity in regions important for reward-processing and salience, that is, in the VS, anterior and posterior cingulate, as well as superior frontal gyrus. Subjective value, that is, WTP was correlated with activity in the ventromedial prefrontal cortex (vmPFC). We find that the anterior cingulate, VS and superior frontal gyrus exhibit task-related increases in functional connectivity to the vmPFC when an FT product was evaluated. Effective connectivity analyses revealed a highly probable directed modulation of the vmPFC by those three regions, suggesting a network which alters valuation processes. We also found a significant taste-placebo effect, with higher experienced taste pleasantness and intensity for FT labeled chocolates. Our results reveal a possible neural mechanism underlying valuation processes of certified food products. The results are important in light of understanding current marketing trends as well as designing

  14. Catalytic Science and Technology in Sustainable Energy II

    DEFF Research Database (Denmark)

    Wang, Yuxin; Xiao, Feng-Shou; Seshan, Kulathu K.

    2017-01-01

    This special issue of Catalysis Today results from four sessions, under the collective theme "Catalysis in Sustainable Energy", of the 2ndInternational Symposium on Catalytic Science and Technology in Sustainable Energy and Environment, held in Tianjin, China during October 12-14, 2016. This bien...... whom the special issue would not have been possible. As the organizer of the EECAT 2016, Y Li expresses his special gratitude to the sponsors, especially Haldor Topsoe and Synfuels China, the participants and the co-organizers for their great contribution to the success of EECAT 2016....

  15. Sustainability of the Benefits Derived from Fadama II Critical ...

    African Journals Online (AJOL)

    USER

    Olaoye, A.D.. Department of Agricultural Extension and Rural Development. University of Ibadan, Nigeria. Abstract. This study investigated the sustainability of the benefits derived from. Critical Ecosystem Management Project in Ogun State. Interview schedule was used to elicit information from 166 respondents randomly ...

  16. Engineering solutions for sustainability materials and resources II

    CERN Document Server

    Mishra, Brajendra; Anderson, Dayan; Sarver, Emily; Neelameggham, Neale

    2016-01-01

    With impending and burgeoning societal issues affecting both developed and emerging nations, the global engineering community has a responsibility and an opportunity to truly make a difference and contribute. The papers in this collection address what materials and resources are integral to meeting basic societal sustainability needs in critical areas of energy, transportation, housing, and recycling. Contributions focus on the engineering answers for cost-effective, sustainable pathways; the strategies for effective use of engineering solutions; and the role of the global engineering community. Authors share perspectives on the major engineering challenges that face our world today; identify, discuss, and prioritize engineering solution needs; and establish how these fit into developing global-demand pressures for materials and human resources.

  17. Sustained Ca2+ signaling and delayed internalization associated with endothelin receptor heterodimers linked through a PDZ finger.

    Science.gov (United States)

    Evans, Nathan J; Walker, Jeffery W

    2008-08-01

    G protein-coupled receptors (GPCRs), including endothelin receptor A (ETA) and B (ETB), may form dimers or higher-order oligomers that profoundly influence signaling. Here we examined a PDZ finger motif within the C-terminus of ETA and its role in heterodimerization with ETB, and in homodimerization with itself, when expressed in HEK293 cells. Receptor dimerization was monitored by (i) fluorescence resonance energy transfer (FRET) between cyan fluorescent protein (CFP) (FRET donor) and tetracysteine/FlAsH (FRET acceptor) fused to the C-termini of ET receptors, and (ii) coimmunoprecipitation of ET receptors after mild detergent solubilization. Mutations in a PDZ finger motif at threonine403/serine404 eliminated FRET and reduced coimmunoprecipitation of heterodimers and homodimers. Functional consequences were evaluated by measuring mobilization of intracellular Ca2+ and internalization of receptors in response to a 10 nmol/L ET-1 challenge. PDZ mutations converted a sustained Ca2+ signal mediated by ETA:ETB heterodimers into a transient response, similar to that observed for homodimers or monomers. Heterodimers containing PDZ mutations were seen to internalize in a similar time domain (approximately 5 min) to the transient Ca2+ elevation and with similar kinetics to internalization of ETA homodimers or monomers. Without the PDZ mutations, heterodimers did not internalize over 15 min, suggesting the intriguing possibility that sustained Ca2+ signaling was a consequence (at least in part) of delayed internalization. The results are consistent with structural models of ETA-receptor dimerization that place threonine403/serine404 of the PDZ finger motif at the interaction interface between heterodimers and homodimers. Sustained Ca2+ signaling and delayed endocytosis of ETA:ETB heterodimers argues strongly for a unique dimer interface that impacts transmembrane signaling and internalization.

  18. Statistical Detection of the He ii Transverse Proximity Effect: Evidence for Sustained Quasar Activity for >25 Million Years

    Directory of Open Access Journals (Sweden)

    Tobias M. Schmidt

    2017-10-01

    Full Text Available The reionization of helium at z ~ 3 is the final phase transition of the intergalactic medium and supposed to be driven purely by quasars. The He ii transverse proximity effect—enhanced He ii transmission in a background sightline caused by the ionizing radiation of a foreground quasar—therefore offers a unique opportunity to probe the morphology of He ii reionization and to investigate the emission properties of quasars, e.g., ionizing emissivity, lifetime and beaming geometry. We use the most-recent HST/COS far-UV dataset of 22 He ii absorption spectra and conduct our own dedicated optical spectroscopic survey to find foreground quasars around these He ii sightlines. Based on a set of 66 foreground quasars, we perform the first statistical analysis of the He ii transverse proximity effect. Despite a large object-to-object variance, our stacking analysis reveals an excess in the average He ii transmission near the foreground quasars at 3σ significance. This statistical evidence for the transverse proximity effect is corroborated by a clear dependence of the signal strength on the inferred He ii ionization rate at the background sightline. Our detection places, based on the transverse light crossing time, a geometrical limit on the quasar lifetime of tQ > 25 Myr. This evidence for sustained activity of luminous quasars is relevant for the morphology of H i and He ii reionization and helps to constrain AGN triggering mechanisms, accretion physics and models of black hole mass assembly. We show how future modeling of the transverse proximity effect can additionally constrain quasar emission geometries and e.g., clarify if the large observed object-to-object variance can be explained by current models of quasar obscuration.

  19. Modeling of surface myoelectric signals--Part II: Model-based signal interpretation.

    Science.gov (United States)

    Merletti, R; Roy, S H; Kupa, E; Roatta, S; Granata, A

    1999-07-01

    Experimental electromyogram (EMG) data from the human biceps brachii were simulated using the model described in [10] of this work. A multichannel linear electrode array, spanning the length of the biceps, was used to detect monopolar and bipolar signals, from which double differential signals were computed, during either voluntary or electrically elicited isometric contractions. For relatively low-level voluntary contractions (10%-30% of maximum force) individual firings of three to four-different motor units were identified and their waveforms were closely approximated by the model. Motor unit parameters such as depth, size, fiber orientation and length, location of innervation and tendonous zones, propagation velocity, and source width were estimated using the model. Two applications of the model are described. The first analyzes the effects of electrode rotation with respect to the muscle fiber direction and shows the possibility of conduction velocity (CV) over- and under-estimation. The second focuses on the myoelectric manifestations of fatigue during a sustained electrically elicited contraction and the interrelationship between muscle fiber CV, spectral and amplitude variables, and the length of the depolarization zone. It is concluded that a) surface EMG detection using an electrode array, when combined with a model of signal propagation, provides a useful method for understanding the physiological and anatomical determinants of EMG waveform characteristics and b) the model provides a way for the interpretation of fatigue plots.

  20. Journal of Sustainable Development of Energy, Water and Environment Systems - Volume II

    Directory of Open Access Journals (Sweden)

    Neven Duić

    2014-12-01

    Full Text Available The Journal of Sustainable Development of Energy, Water and Environment Systems – JSDEWES is an international journal dedicated to the improvement and dissemination of knowledge on methods, policies and technologies for increasing the sustainability of development by de-coupling growth from natural resources and replacing them with knowledge based economy, taking into account its economic, environmental and social pillars, as well as methods for assessing and measuring sustainability of development, regarding energy, transport, water, environment and food production systems and their many combinations. In total 32 manuscripts were published in Volume II, all of them reviewed by at least two reviewers. The Journal of Sustainable Development of Energy, Water and Environment Systems would like to thank reviewers for their contribution to the quality of the published manuscripts.

  1. Calcium signaling induced by angiotensin II in the pancreatic acinar cell line AR42J.

    Science.gov (United States)

    Barnhart, D C; Sarosi, G A; Romanchuk, G; Mulholland, M W

    1999-03-01

    The purpose of this study was to characterize the nature and mechanisms of angiotensin II-evoked calcium signaling in AR42J cells. Cytosolic calcium concentrations were determined using fura-2-based microfluorimetry. Angiotensin II causes elevations in free cytosolic calcium ([Ca2+]i) in the rat pancreatic acinar cell line AR42J. The mechanisms of angiotensin II-evoked calcium signaling were examined using fura-2-based fluorescent digital microscopy. Angiotensin II caused dose-dependent increments in [Ca2+]i over a concentration range of 0.1-1,000 nM, with an average increment of 243 +/- 16 nM at an angiotensin II concentration of 1,000 nM. Dup753, an AT1-specific antagonist, inhibited angiotensin II-evoked signaling, whereas the AT2 antagonist PD123,319 had no effect. Preincubation with the phospholipase C inhibitor U73122 reduced the response in [Ca2+]i to 25% of that of the control. Thapsigargin abolished angiotensin II-evoked calcium signaling. The inositol 1,4,5-trisphosphate receptor antagonist heparin introduced by radiofrequency electroporation inhibited responses to 46 +/- 6% of controls. Angiotensin II-evoked signals were reduced in magnitude and duration by elimination of Ca2+ from the extracellular buffer. Preincubation with pertussis toxin (100 ng/ml) had no effect. Angiotensin II did not stimulate cyclic AMP or suppress vasoactive intestinal peptide stimulated cyclic AMP production over the concentration range that caused Ca2+ signaling.

  2. Prerequisites for Affective Signal Processing (ASP) - Part II

    NARCIS (Netherlands)

    van den Broek, Egon; Janssen, Joris H.; Healey, Jennifer A.; van der Zwaag, Marjolein; Fred, A.; Filipe, J.; Gamboa, H.

    2010-01-01

    Last year, in van den Broek et al. (2009a), a start was made with defining prerequisites for affective signal processing (ASP). Four prerequisites were identified: validation (e.g., mapping of constructs on signals), triangulation, a physiology-driven approach, and contributions of the signal

  3. Differences in consumer perspectives how sustainable food consumption is perceived and signalled in the prevailing consumer culture : among Generation Y

    OpenAIRE

    Happonen, Ville

    2016-01-01

    This thesis investigates Generation Y sustainable food consumers in the prevailing consumer culture and their differences in signalling and perceiving sustainability. The reasons why they engaged to a sustainable diet and the possible conflicts around it were also studied. Relevant contexts around consumer culture, possessions, identities and Generation Y regarding sustainable food consumption were presented as the theoretical framework. The focus was on Generation Y consumers in order to...

  4. Mathematical modeling of sustainable synaptogenesis by repetitive stimuli suggests signaling mechanisms in vivo.

    Directory of Open Access Journals (Sweden)

    Hiromu Takizawa

    Full Text Available The mechanisms of long-term synaptic maintenance are a key component to understanding the mechanism of long-term memory. From biological experiments, a hypothesis arose that repetitive stimuli with appropriate intervals are essential to maintain new synapses for periods of longer than a few days. We successfully reproduce the time-course of relative numbers of synapses with our mathematical model in the same conditions as biological experiments, which used Adenosine-3', 5'-cyclic monophosphorothioate, Sp-isomer (Sp-cAMPS as external stimuli. We also reproduce synaptic maintenance responsiveness to intervals of Sp-cAMPS treatment accompanied by PKA activation. The model suggests a possible mechanism of sustainable synaptogenesis which consists of two steps. First, the signal transduction from an external stimulus triggers the synthesis of a new signaling protein. Second, the new signaling protein is required for the next signal transduction with the same stimuli. As a result, the network component is modified from the first network, and a different signal is transferred which triggers the synthesis of another new signaling molecule. We refer to this hypothetical mechanism as network succession. We build our model on the basis of two hypotheses: (1 a multi-step network succession induces downregulation of SSH and COFILIN gene expression, which triggers the production of stable F-actin; (2 the formation of a complex of stable F-actin with Drebrin at PSD is the critical mechanism to achieve long-term synaptic maintenance. Our simulation shows that a three-step network succession is sufficient to reproduce sustainable synapses for a period longer than 14 days. When we change the network structure to a single step network, the model fails to follow the exact condition of repetitive signals to reproduce a sufficient number of synapses. Another advantage of the three-step network succession is that this system indicates a greater tolerance of parameter

  5. Sustained nitric oxide (NO)-releasing compound reverses dysregulated NO signal transduction in priapism

    Science.gov (United States)

    Lagoda, Gwen; Sezen, Sena F.; Hurt, K. Joseph; Cabrini, Marcelo R.; Mohanty, Dillip K.; Burnett, Arthur L.

    2014-01-01

    We evaluated the therapeutic potential of a sustained nitric oxide (NO)-releasing compound to correct the molecular hallmarks and pathophysiology of priapism, an important but poorly characterized erectile disorder. 1,5-Bis-(dihexyl-N-nitrosoamino)-2,4-dinitrobenzene (C6′) and an inactive form of the compound [1,5-bis-(dihexylamino)-2,4-dinitrobenzene (C6)] were tested in neuronal cell cultures and penile lysates for NO release (Griess assay) and biological activity (cGMP production). The effect of local depot C6′ or C6 was evaluated in mice with a priapic phenotype due to double neuronal and endothelial NO synthase deletion (dNOS−/−) or human sickle hemoglobin transgenic expression (Sickle). Changes in NO signaling molecules and reactive oxygen species (ROS) surrogates were assessed by Western blot. The physiological response after C6′ treatment was assessed using an established model of electrically stimulated penile erection. C6′ generated NO, increased cGMP, and dose dependently increased NO metabolites. C6′ treatment reversed abnormalities in key penile erection signaling molecules, including phosphodiesterase type 5, phosphorylated endothelial nitric oxide synthase, and phosphorylated vasodilator-stimulated phosphoprotein. In Sickle mice, C6′ also attenuated the increased ROS markers gp91phox, 4-hydroxynonenal, and 3-nitrotyrosine. Finally, C6′ corrected the excessive priapic erection response of dNOS−/− mice. Exogenous sustained NO release from C6′ corrects pathological erectile signaling in mouse models of priapism and suggests novel approaches to human therapy.—Lagoda, G., Sezen, S. F., Hurt, K. J., Cabrini, M. R., Mohanty, D. K., Burnett, A. L. Sustained nitric oxide (NO)-releasing compound reverses dysregulated NO signal transduction in priapism. PMID:24076963

  6. Activation of MyD88 Signaling upon Staphylococcal Enterotoxin Binding to MHC Class II Molecules

    Science.gov (United States)

    2011-01-20

    Salisbury, UK), and was prepared under GMP condition, endotoxin free and stored at 250uC. Escherichia coli LPS (055:B5) was purchased from Difco...29. Spertini F, Chatila T, Geha RS (1992) Signals delivered via MHC class II molecules synergize with signals delivered via TCR/CD3 to cause

  7. Real-Time Translocation and Function of PKCβII Isoform in Response to Nociceptive Signaling via the TRPV1 Pain Receptor

    Directory of Open Access Journals (Sweden)

    Basil D. Roufogalis

    2011-11-01

    Full Text Available Serine/threonine protein kinase C βII isoform (PKCβII or the pain receptor transient receptor potential vanilloid 1 (TRPV1 have been separately implicated in mediating heat hyperalgesia during inflammation or diabetic neuropathy. However, detailed information on the role of PKC βII in nociceptive signaling mediated by TRPV1 is lacking. This study presents evidence for activation and translocation of the PKC βII isoform as a signaling event in nociception mediated by activation of TRPV1 by capsaicin. We show that capsaicin induces translocation of cytosolic PKCβII isoform fused with enhanced green fluorescence protein (PKCβII-EGFP in dorsal root ganglion (DRG neurons. We also show capsaicin-induced translocation in Chinese Hamster Ovarian (CHO cells co-transfected with TRPV1 and PKCβII-EGFP, but not in CHO cells expressing PKCβII-EGFP alone. By contrast, the PKC activator phorbol-12-myristate-13-acetate (PMA induced translocation of PKCβII-EGFP which was sustained and independent of calcium or TRPV1. In addition PMA-induced sensitization of TRPV1 to capsaicin response in DRG neurons was attenuated by PKCβII blocker CGP 53353. Capsaicin response via TRPV1 in the DRG neurons was confirmed by TRPV1 antagonist AMG 9810. These results suggested a novel and potential signaling link between PKCβII and TRPV1. These cell culture models provide a platform for investigating mechanisms of painful neuropathies mediated by nociceptors expressing the pain sensing gene TRPV1, and its regulation by the PKC isoform PKCβII.

  8. ZAP-70 and p72syk are signaling response elements through MHC class II molecules

    DEFF Research Database (Denmark)

    Kanner, S B; Grosmaire, L S; Blake, J

    1995-01-01

    to antibody induced receptor ligation, bacterial superantigen (SEA and SEB) treatment of HLA-DR+ T-cells stimulated ZAP-70 tyrosine phosphorylation, consistent with class II transmembrane signaling by ligation of HLA-DR and V beta in cis. Modulation of the TCR/CD3 led to abrogation of class II induced ZAP-70......Ligation of major histocompatibility complex (MHC) class II antigens expressed on antigen-activated human CD4+ T-lymphocytes induces early signal transduction events including the activation of tyrosine kinases, the tyrosine phosphorylation of phospholipase-C gamma 1 and the mobilization...... of intracellular calcium. Similar responses have been observed in B-cells following stimulation of MHC class II molecules, including the increased production of intracellular cAMP. In this report, we demonstrate that the ZAP-70 tyrosine kinase is a responsive signaling element following cross-linking of HLA...

  9. Protein kinase C contributes to desensitization of ANG II signaling in adult rat cardiac fibroblasts.

    Science.gov (United States)

    Meszaros, J G; Raphael, R; Lio, F M; Brunton, L L

    2000-12-01

    We have studied G(q)-linked ANG II signaling [inositol phosphate (IP) accumulation, Ca(2+) mobilization] in primary cultures of rat cardiac fibroblasts (CFs) and have found that ANG II initiates a protein kinase C (PKC)-mediated negative feedback loop that rapidly terminates the ANG II response. Pharmacological inhibition of PKC by staurosporine and GF-109203X doubled IP production over that achieved in response to ANG II alone. Inhibition of PKC also led to larger Ca(2+) transients in response to ANG II, suggesting that Ca(2+) mobilization was proportional to G(q)-phospholipase C-IP(3) activity under the conditions studied. Depletion of cellular PKC by overnight treatment with phorbol 12-myristate 13-acetate (PMA) similarly augmented ANG II-induced IP production. Acute activation of PKC by PMA halved IP formation, with an EC(50) approximately 1 nM; 4alpha-PMA was inactive. Time course data demonstrated that ANG II-mediated IP production fully desensitized within 30 s; PKC inhibition reduced the rate and extent of this desensitization. In cells desensitized to ANG II, a purinergic agonist still mobilized intracellular Ca(2+), indicating that desensitization was homologous. The ANG II-induced Ca(2+) signal was fully resensitized within 30 min. The data demonstrate that a large portion of the IP-Ca(2+) responses of rat CFs to ANG II are short-lived because of rapid, PKC-mediated desensitization.

  10. The origin of split EPR signals in the Ca2+-depleted photosystem II.

    Science.gov (United States)

    Mino, Hiroyuki; Itoh, Shigeru

    2005-06-01

    A light-driven reaction model for the Ca2+-depleted Photosystem (PS) II is proposed to explain the split signal observed in electron paramagnetic resonance (EPR) spectra based on a comparison of EPR assignments with recent x-ray structural data. The split signal has a splitting linewidth of 160 G at around g = 2 and is seen upon illumination of the Ca2+-depleted PS II in the S2 state associated with complete or partial disappearance of the S2 state multiline signal. Another g=2 broad ESR signal with a 110 G linewidth was produced by 245 K illumination for a short period in the Ca2+-depleted PS II in S1 state. At the same time a normal YZ . radical signal was also efficiently trapped. The g=2 broad signal is attributed to an intermediate S1X. state in equilibrium with the trapped YZ . radical. Comparison with x-ray structural data suggests that one of the split signals (doublet signal) is attributable to interaction between His 190 and the YZ . radical, and other signals is attributable to interaction between His 337 and the manganese cluster, providing further clues as to the mechanism of water oxidation in photosynthetic oxygen evolution.

  11. Endogenous signaling by omega-3 docosahexaenoic acid-derived mediators sustains homeostatic synaptic and circuitry integrity.

    Science.gov (United States)

    Bazan, Nicolas G; Musto, Alberto E; Knott, Eric J

    2011-10-01

    The harmony and function of the complex brain circuits and synapses are sustained mainly by excitatory and inhibitory neurotransmission, neurotrophins, gene regulation, and factors, many of which are incompletely understood. A common feature of brain circuit components, such as dendrites, synaptic membranes, and other membranes of the nervous system, is that they are richly endowed in docosahexaenoic acid (DHA), the main member of the omega-3 essential fatty acid family. DHA is avidly retained and concentrated in the nervous system and known to play a role in neuroprotection, memory, and vision. Only recently has it become apparent why the surprisingly rapid increases in free (unesterified) DHA pool size take place at the onset of seizures or brain injury. This phenomenon began to be clarified by the discovery of neuroprotectin D1 (NPD1), the first-uncovered bioactive docosanoid formed from free DHA through 15-lipoxygenase-1 (15-LOX-1). NPD1 synthesis includes, as agonists, oxidative stress and neurotrophins. The evolving concept is that DHA-derived docosanoids set in motion endogenous signaling to sustain homeostatic synaptic and circuit integrity. NPD1 is anti-inflammatory, displays inflammatory resolving activities, and induces cell survival, which is in contrast to the pro-inflammatory actions of the many of omega-6 fatty acid family members. We highlight here studies relevant to the ability of DHA to sustain neuronal function and protect synapses and circuits in the context of DHA signalolipidomics. DHA signalolipidomics comprises the integration of the cellular/tissue mechanism of DHA uptake, its distribution among cellular compartments, the organization and function of membrane domains containing DHA phospholipids, and the precise cellular and molecular events revealed by the uncovering of signaling pathways regulated by docosanoids endowed with prohomeostatic and cell survival bioactivity. Therefore, this approach offers emerging targets for prevention

  12. Reactive oxygen species and angiotensin II signaling in vascular cells: implications in cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Touyz R.M.

    2004-01-01

    Full Text Available Diseases such as hypertension, atherosclerosis, hyperlipidemia, and diabetes are associated with vascular functional and structural changes including endothelial dysfunction, altered contractility and vascular remodeling. Cellular events underlying these processes involve changes in vascular smooth muscle cell (VSMC growth, apoptosis/anoikis, cell migration, inflammation, and fibrosis. Many factors influence cellular changes, of which angiotensin II (Ang II appears to be amongst the most important. The physiological and pathophysiological actions of Ang II are mediated primarily via the Ang II type 1 receptor. Growing evidence indicates that Ang II induces its pleiotropic vascular effects through NADPH-driven generation of reactive oxygen species (ROS. ROS function as important intracellular and intercellular second messengers to modulate many downstream signaling molecules, such as protein tyrosine phosphatases, protein tyrosine kinases, transcription factors, mitogen-activated protein kinases, and ion channels. Induction of these signaling cascades leads to VSMC growth and migration, regulation of endothelial function, expression of pro-inflammatory mediators, and modification of extracellular matrix. In addition, ROS increase intracellular free Ca2+ concentration ([Ca2+]i, a major determinant of vascular reactivity. ROS influence signaling molecules by altering the intracellular redox state and by oxidative modification of proteins. In physiological conditions, these events play an important role in maintaining vascular function and integrity. Under pathological conditions ROS contribute to vascular dysfunction and remodeling through oxidative damage. The present review focuses on the biology of ROS in Ang II signaling in vascular cells and discusses how oxidative stress contributes to vascular damage in cardiovascular disease.

  13. Peach (Prunus persica) extract inhibits angiotensin II-induced signal transduction in vascular smooth muscle cells.

    Science.gov (United States)

    Kono, Ryohei; Okuno, Yoshiharu; Nakamura, Misa; Inada, Ken-ichi; Tokuda, Akihiko; Yamashita, Miki; Hidaka, Ryu; Utsunomiya, Hirotoshi

    2013-08-15

    Angiotensin II (Ang II) is a vasoactive hormone that has been implicated in cardiovascular diseases. Here, the effect of peach, Prunus persica L. Batsch, pulp extract on Ang II-induced intracellular Ca(2+) mobilization, reactive oxygen species (ROS) production and signal transduction events in cultured vascular smooth muscle cells (VSMCs) was investigated. Pretreatment of peach ethyl acetate extract inhibited Ang II-induced intracellular Ca(2+) elevation in VSMCs. Furthermore, Ang II-induced ROS generation, essential for signal transduction events, was diminished by the peach ethyl acetate extract. The peach ethyl acetate extract also attenuated the Ang II-induced phosphorylation of epidermal growth factor receptor and myosin phosphatase target subunit 1, both of which are associated with atherosclerosis and hypertension. These results suggest that peach ethyl acetate extract may have clinical potential for preventing cardiovascular diseases by interfering with Ang II-induced intracellular Ca(2+) elevation, the generation of ROS, and then blocking signal transduction events. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Bayesian analysis. II. Signal detection and model selection

    Science.gov (United States)

    Bretthorst, G. Larry

    In the preceding. paper, Bayesian analysis was applied to the parameter estimation problem, given quadrature NMR data. Here Bayesian analysis is extended to the problem of selecting the model which is most probable in view of the data and all the prior information. In addition to the analytic calculation, two examples are given. The first example demonstrates how to use Bayesian probability theory to detect small signals in noise. The second example uses Bayesian probability theory to compute the probability of the number of decaying exponentials in simulated T1 data. The Bayesian answer to this question is essentially a microcosm of the scientific method and a quantitative statement of Ockham's razor: theorize about possible models, compare these to experiment, and select the simplest model that "best" fits the data.

  15. Neurophysiological Signals of Ignoring and Attending Are Separable and Related to Performance during Sustained Intersensory Attention

    Science.gov (United States)

    Lenartowicz, Agatha; Simpson, Gregory V.; Haber, Catherine M.; Cohen, Mark S.

    2017-01-01

    The ability to attend to an input selectively while ignoring distracting sensations is thought to depend on the coordination of two processes: enhancement of target signals and attenuation of distractor signals. This implies that attending and ignoring may be dissociable neural processes and that they make separable contributions to behavioral outcomes of attention. In this study, we tested these hypotheses in the context of sustained attention by measuring neurophysiological responses to attended and ignored stimuli in a noncued, continuous, audiovisual selective attention task. We compared these against responses during a passive control to quantify effects of attending and ignoring separately. In both sensory modalities, responses to ignored stimuli were attenuated relative to a passive control, whereas responses to attended stimuli were enhanced. The scalp topographies and brain activations of these modulatory effects were consistent with the sensory regions that process each modality. They also included parietal and prefrontal activations that suggest these effects arise from interactions between top–down and sensory cortices. Most importantly, we found that both attending and ignoring processes contributed to task accuracy and that these effects were not correlated—suggesting unique neural trajectories. This conclusion was supported by the novel observation that attending and ignoring differed in timing and in active cortical regions. The data provide direct evidence for the separable contributions of attending and ignoring to behavioral outcomes of attention control during sustained intersensory attention. PMID:24666167

  16. Urotensin II-induced signaling involved in proliferation of vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Myriam Iglewski

    2010-08-01

    Full Text Available Myriam Iglewski, Stephen R GrantDepartment of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, Texas, USAAbstract: The urotensin II receptor, bound by the ligand urotensin II, generates second ­messengers, ie, inositol triphosphate and diacylglycerol, which stimulate the subsequent release of calcium (Ca2+ in vascular smooth muscle cells. Ca2+ influx leads to the activation of Ca2+-dependent kinases (CaMK via calmodulin binding, resulting in cellular proliferation. We hypothesize that urotensin II signaling in pulmonary arterial vascular smooth muscle cells (Pac1 and primary aortic vascular smooth muscle cells (PAVSMC results in phosphorylation of Ca2+/calmodulin-dependent kinases leading to cellular proliferation. Exposure of Pac1 cultures to urotensin II increased intracellular Ca2+, subsequently activating Ca2+/calmodulin-dependent kinase kinase (CaMKK, and Ca2+/calmodulin-dependent kinase Type I (CaMKI, extracellular signal-regulated kinase (ERK 1/2, and protein kinase D. Treatment of Pac1 and PAVSMC with urotensin II increased proliferation as measured by 3H-thymidine uptake. The urotensin II-induced increase in 3H-thymidine incorporation was inhibited by a CaMKK inhibitor. Taken together, our results demonstrate that urotensin II stimulation of smooth muscle cells leads to a Ca2+/calmodulin-dependent kinase-mediated increase in cellular proliferation.Keywords: urotensin II receptor, CaMKI, hypertrophy, CaMKK, protein kinase D

  17. Angiotensin II increases phosphodiesterase 5A expression in vascular smooth muscle cells: A mechanism by which angiotensin II antagonizes cGMP signaling

    Science.gov (United States)

    Kim, Dongsoo; Aizawa, Toru; Wei, Heng; Pi, Xinchun; Rybalkin, Sergei D.; Berk, Bradford C.; Yan, Chen

    2014-01-01

    Angiotensin II (Ang II) and nitric oxide (NO)/natriuretic peptide (NP) signaling pathways mutually regulate each other. Imbalance of Ang II and NO/NP has been implicated in the pathophysiology of many vascular diseases. cGMP functions as a key mediator in the interaction between Ang II and NO/NP. Cyclic nucleotide phosphodiesterase 5A (PDE5A) is important in modulating cGMP signaling by hydrolyzing cGMP in vascular smooth muscle cells (VSMC). Therefore, we examined whether Ang II negatively modulates intracellular cGMP signaling in VSMC by regulating PDE5A. Ang II rapidly and transiently increased PDE5A mRNA levels in rat aortic VSMC. Upregulation of PDE5A mRNA was associated with a time-dependent increase of both PDE5 protein expression and activity. Increased PDE5A mRNA level was transcription-dependent and mediated by the Ang II type 1 receptor. Ang II-mediated activation of extracellular signal-regulated kinases 1/2 (ERK1/2) was essential for Ang II-induced PDE5A upregulation. Pretreatment of VSMC with Ang II inhibited C-type NP (CNP) stimulated cGMP signaling, such as cGMP dependent protein kinase (PKG)-mediated phosphorylation of vasodilator-stimulated-phosphoprotein (VASP). Ang II-mediated inhibition of PKG was blocked when PDE5 activity was decreased by selective PDE5 inhibitors, suggesting that upregulation of PDE5A expression is an important mechanism for Ang II to attenuate cGMP signaling. PDE5A may also play a critical role in the growth promoting effects of Ang II because inhibition of PDE5A activity significantly decreased Ang II-stimulated VSMC growth. These observations establish a new mechanism by which Ang II antagonizes cGMP signaling and stimulates VSMC growth. PMID:15623434

  18. Limiting characteristics of a superconducting quantum interferometer. I - Signal characteristic. II - Signal-to-noise ratio

    Science.gov (United States)

    Butikov, E. I.; Feofilov, S. P.

    1980-11-01

    An investigation is presented of a dc SQUID with two Josephson junctions in a system for measuring small changes of a magnetic field with low-frequency modulation of the magnetic flux. Idealized theoretical signal characteristics are obtained, and their dependence on the modes of operation and parameters of the SQUID are studied. These characteristics are used to determine the minimum detectable changes of magnetic flux characterizing the limiting sensitivity of the SQUID. The spectral density of thermal noise is obtained for the low-frequency range which constrains the limiting sensitivity; the signal/noise ratio is studied as a function of the operating modes and parameters of the SQUID.

  19. DDR1 signaling is essential to sustain Stat5 function during lactogenesis.

    Science.gov (United States)

    Faraci-Orf, Elena; McFadden, Catherine; Vogel, Wolfgang F

    2006-01-01

    Postnatal development of the mammary gland is achieved by an interplay of endocrine and extracellular matrix-derived signals. Despite intense research, a comprehensive understanding of the temporal and spatial coordination of these hormonal and basement membrane stimuli is still lacking. Here, we address the role of the collagen-receptor DDR1 in integrating extracellular matrix-derived signaling with the lactogenic pathway initiated by the prolactin receptor. We found that stimulation of DDR1-overexpressing mammary epithelial HC11 cells with collagen and prolactin resulted in stronger and more sustained induction of Stat5 phosphorylation as compared to control cells. Enhanced Stat5 activity in HC11-DDR1 cells correlated with increased beta-casein gene expression. In contrast, cells derived from DDR1-null mice showed reduced Stat5 activation upon lactogenic stimulation and completely failed to induce beta-casein expression. The cell-autonomous role of DDR1 in controlling ductal branching and alveologenesis prior to the onset of lactogenesis was corroborated by mammary tissue transplantation experiments. Our results show that aside from hormone- and cytokine receptors, DDR1 signaling establishes a third matrix-derived pathway vital to maintain mammary gland function. (c) 2005 Wiley-Liss, Inc.

  20. Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments

    Science.gov (United States)

    Richter, David; Moraga, Ignacio; Winkelmann, Hauke; Birkholz, Oliver; Wilmes, Stephan; Schulte, Markos; Kraich, Michael; Kenneweg, Hella; Beutel, Oliver; Selenschik, Philipp; Paterok, Dirk; Gavutis, Martynas; Schmidt, Thomas; Garcia, K. Christopher; Müller, Thomas D.; Piehler, Jacob

    2017-07-01

    The spatiotemporal organization of cytokine receptors in the plasma membrane is still debated with models ranging from ligand-independent receptor pre-dimerization to ligand-induced receptor dimerization occurring only after receptor uptake into endosomes. Here, we explore the molecular and cellular determinants governing the assembly of the type II interleukin-4 receptor, taking advantage of various agonists binding the receptor subunits with different affinities and rate constants. Quantitative kinetic studies using artificial membranes confirm that receptor dimerization is governed by the two-dimensional ligand-receptor interactions and identify a critical role of the transmembrane domain in receptor dimerization. Single molecule localization microscopy at physiological cell surface expression levels, however, reveals efficient ligand-induced receptor dimerization by all ligands, largely independent of receptor binding affinities, in line with the similar STAT6 activation potencies observed for all IL-4 variants. Detailed spatiotemporal analyses suggest that kinetic trapping of receptor dimers in actin-dependent microcompartments sustains robust receptor dimerization and signalling.

  1. Neutrophilic Lung Inflammation Suppressed by Picroside II Is Associated with TGF-β Signaling

    Science.gov (United States)

    Noh, Soohwan; Ahn, Kyung-Seop; Oh, Sei-Ryang

    2015-01-01

    Although acute lung injury (ALI) is a leading cause of death in intensive care unit, effective pharmacologic means to treat ALI patients are lacking. The rhizome of Picrorhiza scrophulariiflora used in a traditional herbal medicine in Asian countries has been shown to have anti-inflammatory function, and picroside II (PIC II) is known as a major constituent in the plant. Here, we examined whether PIC II has an anti-inflammatory activity, which is applicable for treating ALI. We found that although it is not significantly effective in suppressing proinflammatory factor NF-κB or in activating anti-inflammatory factor Nrf2, PIC II induced the phosphorylation of Smad 2, with concomitant increase of luciferase activity from SBE luciferase reporter in RAW 264.7 cells. H&E staining of lung, differential counting of cells in bronchoalveolar lavage fluid, and semiquantitative RT-PCR analyses of lung tissues show that an intratracheal (i.t.) spraying of PIC II suppressed neutrophilic inflammation and the expression of proinflammatory cytokine genes in the lung, which were elicited by an i.t. LPS instillation to the lung. In addition, PIC II treatment increased the phosphorylation of Smad 2 in the lung tissue. Together, our results suggest that PIC II plays a role as an anti-inflammatory constituent in P. scrophulariiflora, whose activity is associated at least in part with TGF-β signaling. PMID:26617662

  2. Neutrophilic Lung Inflammation Suppressed by Picroside II Is Associated with TGF-β Signaling

    Directory of Open Access Journals (Sweden)

    Soohwan Noh

    2015-01-01

    Full Text Available Although acute lung injury (ALI is a leading cause of death in intensive care unit, effective pharmacologic means to treat ALI patients are lacking. The rhizome of Picrorhiza scrophulariiflora used in a traditional herbal medicine in Asian countries has been shown to have anti-inflammatory function, and picroside II (PIC II is known as a major constituent in the plant. Here, we examined whether PIC II has an anti-inflammatory activity, which is applicable for treating ALI. We found that although it is not significantly effective in suppressing proinflammatory factor NF-κB or in activating anti-inflammatory factor Nrf2, PIC II induced the phosphorylation of Smad 2, with concomitant increase of luciferase activity from SBE luciferase reporter in RAW 264.7 cells. H&E staining of lung, differential counting of cells in bronchoalveolar lavage fluid, and semiquantitative RT-PCR analyses of lung tissues show that an intratracheal (i.t. spraying of PIC II suppressed neutrophilic inflammation and the expression of proinflammatory cytokine genes in the lung, which were elicited by an i.t. LPS instillation to the lung. In addition, PIC II treatment increased the phosphorylation of Smad 2 in the lung tissue. Together, our results suggest that PIC II plays a role as an anti-inflammatory constituent in P. scrophulariiflora, whose activity is associated at least in part with TGF-β signaling.

  3. Thymosin β4 Prevents Angiotensin II-Induced Cardiomyocyte Growth by Regulating Wnt/WISP Signaling.

    Science.gov (United States)

    Li, Li; Guleria, Rakeshwar S; Thakur, Suresh; Zhang, Cheng-Lin; Pan, Jing; Baker, Kenneth M; Gupta, Sudhiranjan

    2016-08-01

    Thymosin beta-4 (Tβ4) is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. However, the role of Tβ4 in cardiomyocyte hypertrophy is currently unknown. The purpose of this study was to determine the cardio-protective effect of Tβ4 in angiotensin II (Ang II)-induced cardiomyocyte growth. Neonatal rat ventricular cardiomyocytes (NRVM) were pretreated with Tβ4 followed by Ang II stimulation. Cell size, hypertrophy marker gene expression and Wnt signaling components, β-catenin, and Wnt-induced secreted protein-1 (WISP-1) were evaluated by quantitative real-time PCR, Western blotting and fluorescent microscopy. Pre-treatment of Tβ4 resulted in reduction of cell size, hypertrophy marker genes and Wnt-associated gene expression, and protein levels; induced by Ang II in cardiomyocyte. WISP-1 was overexpressed in NRVM and, the effect of Tβ4 in Ang II-induced cardiomyocyte growth was evaluated. WISP-1 overexpression promoted cardiomyocytes growth and was reversed by pretreatment with Tβ4. This is the first report which demonstrates that Tβ4 targets Wnt/WISP-1 to protect Ang II-induced cardiomyocyte growth. J. Cell. Physiol. 231: 1737-1744, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  4. Use of modulated excitation signals in ultrasound. Part II: Design and performance for medical imaging applications

    DEFF Research Database (Denmark)

    Misaridis, Thanassis; Jensen, Jørgen Arendt

    2005-01-01

    For pt.I, see ibid., vol.52, no.2, p.177-91 (2005). In the first paper, the superiority of linear FM signals was shown in terms of signal-to-noise ratio and robustness to tissue attenuation. This second paper in the series of three papers on the application of coded excitation signals in medical....... The method is evaluated first for resolution performance and axial sidelobes through simulations with the program Field II. A coded excitation ultrasound imaging system based on a commercial scanner and a 4 MHz probe driven by coded sequences is presented and used for the clinical evaluation of the coded....... The paper also presents acquired images, using complementary Golay codes, that show the deleterious effects of attenuation on binary codes when processed with a matched filter, als- - o confirmed by the presented simulated images....

  5. Class II HDACs mediate CaMK-dependent signaling to NRSF in ventricular myocytes.

    Science.gov (United States)

    Nakagawa, Yasuaki; Kuwahara, Koichiro; Harada, Masaki; Takahashi, Nobuki; Yasuno, Shinji; Adachi, Yuichiro; Kawakami, Rika; Nakanishi, Michio; Tanimoto, Keiji; Usami, Satoru; Kinoshita, Hideyuki; Saito, Yoshihiko; Nakao, Kazuwa

    2006-12-01

    We recently reported that a transcriptional repressor, neuron-restrictive silencer factor (NRSF), represses expression of fetal cardiac genes, including atrial and brain natriuretic peptide (ANP and BNP), by recruiting class I histone deacetylase (HDAC) and that attenuation of NRSF-mediated repression contributes to the reactivation of fetal gene expression during cardiac hypertrophy. The molecular mechanism by which the activity of the NRSF-HDAC complex is inhibited in cardiac hypertrophy remains unresolved, however. In the present study, we show that class II HDACs (HDAC4 and 5), which are Ca/calmodulin-dependent kinase (CaMK)-responsive repressors of hypertrophic signaling, associate with NRSF and participate in NRSF-mediated repression. Blockade of the CaMK-class II HDAC signaling pathway using a CaMK-resistant HDAC5 mutant, a CaMK inhibitor (KN62) or a dominant-negative CaMK mutant inhibited ET-1-inducible ANP and BNP promoter activity, but that inhibitory effect was abolished by mutation of the neuron-restrictive silencer element (NRSE) within the ANP and BNP promoter. In addition, adenovirus-mediated expression of a dominant-negative NRSF mutant abolished the inhibitory effect of KN62 on ET-1-inducible endogenous ANP gene expression in ventricular myocytes. Finally, the interaction between NRSF and class II HDACs was decreased in both in vitro and in vivo models of cardiac hypertrophy. These findings show that ET-1-induced CaMK signaling disrupts class II HDAC-NRSF repressor complexes, thereby enabling activation of ANP and BNP gene transcription in ventricular myocytes, and shed light on a novel mechanism by which the fetal cardiac gene program is reactivated.

  6. Thrombin promotes sustained signaling and inflammatory gene expression through the CDC25 and Ras-associating domains of phospholipase Cϵ.

    Science.gov (United States)

    Dusaban, Stephanie S; Kunkel, Maya T; Smrcka, Alan V; Brown, Joan Heller

    2015-10-30

    Phospholipase C-epsilon (PLCϵ) plays a critical role in G-protein-coupled receptor-mediated inflammation. In addition to its ability to generate the second messengers inositol 1,4,5-trisphosphate and diacylglycerol, PLCϵ, unlike the other phospholipase C family members, is activated in a sustained manner. We hypothesized that the ability of PLCϵ to function as a guanine nucleotide exchange factor (GEF) for Rap1 supports sustained downstream signaling via feedback of Rap1 to the enzyme Ras-associating (RA2) domain. Using gene deletion and adenoviral rescue, we demonstrate that both the GEF (CDC25 homology domain) and RA2 domains of PLCϵ are required for long term protein kinase D (PKD) activation and subsequent induction of inflammatory genes. PLCϵ localization is largely intracellular and its compartmentalization could contribute to its sustained activation. Here we show that localization of PLCϵ to the Golgi is required for activation of PKD in this compartment as well as for subsequent induction of inflammatory genes. These data provide a molecular mechanism by which PLCϵ mediates sustained signaling and by which astrocytes mediate pathophysiological inflammatory responses. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Sustained Adenosine Exposure Causes Lung Endothelial Barrier Dysfunction via Nucleoside Transporter–Mediated Signaling

    Science.gov (United States)

    Newton, Julie; Hsiao, Vivian; Shamirian, Paul; Blackburn, Michael R.; Pedroza, Mesias

    2012-01-01

    Previous studies by our group as well as others have shown that acute adenosine exposure enhances lung vascular endothelial barrier integrity and protects against increased permeability lung edema. In contrast, there is growing evidence that sustained adenosine exposure has detrimental effects on the lungs, including lung edema. It is well established that adenosine modulates lung inflammation. However, little is known concerning the effect of sustained adenosine exposure on lung endothelial cells (ECs), which are critical to the maintenance of the alveolar–capillary barrier. We show that exogenous adenosine plus adenosine deaminase inhibitor caused sustained elevation of adenosine in lung ECs. This sustained adenosine exposure decreased EC barrier function, elevated cellular reactive oxygen species levels, and activated p38, JNK, and RhoA. Inhibition of equilibrative nucleoside transporters (ENTs) prevented sustained adenosine-induced p38 and JNK activation and EC barrier dysfunction. Inhibition of p38, JNK, or RhoA also partially attenuated sustained adenosine-induced EC barrier dysfunction. These data indicate that sustained adenosine exposure causes lung EC barrier dysfunction via ENT-dependent intracellular adenosine uptake and subsequent activation of p38, JNK, and RhoA. The antioxidant N-acetylcysteine and the NADPH inhibitor partially blunted sustained adenosine-induced JNK activation but were ineffective in attenuation of p38 activation or barrier dysfunction. p38 was activated exclusively in mitochondria, whereas JNK was activated in mitochondria and cytoplasm by sustained adenosine exposure. Our data further suggest that sustained adenosine exposure may cause mitochondrial oxidative stress, leading to activation of p38, JNK, and RhoA in mitochondria and resulting in EC barrier dysfunction. PMID:22744860

  8. Application for TJ-II Signals Visualization: User's Guide; Aplicacion para la Visualizacion de Senales de TJ-II: Guia del Usuario

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, E.; Portas, A. B.; Vega, J. [Ciemat, Madrid (Spain)

    2000-07-01

    In this documents are described the functionalities of the application developed by the Data Acquisition Group for TJ-II signal visualization. There are two versions of the application, the On-line version, used for signal visualization during TJ-II operation, and the Off-line version, used for signal visualization without TJ-II operation. Both versions of the application consist in a graphical user interface developed for X/Motif, in which most of the actions can be done using the mouse buttons. The functionalities of both versions of the application are described in this user's guide, beginning at the application start-up and explaining in detail all the options that it provides and the actions that can be done with each graphic control. (Author) 8 refs.

  9. Type II cGMP‑dependent protein kinase inhibits EGF‑induced JAK/STAT signaling in gastric cancer cells.

    Science.gov (United States)

    Wu, Min; Wu, Yan; Lan, Ting; Jiang, Lu; Qian, Hai; Chen, Yongchang

    2016-08-01

    Previous research has demonstrated that type II cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG II) inhibited epidermal growth factor (EGF)‑initiated signal transduction of MAPK‑mediated, PI3K/Akt‑mediated and PLCγ1‑mediated pathways through blocking EGF‑induced phosphorylation/activation of EGF receptor (EGFR). As EGF/EGFR signaling also initiated signal transduction of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT)‑mediated pathway, the present study was performed to investigate whether PKG II exerts an inhibitory effect this pathway. AGS human gastric cancer cell line was infected with adenoviral constructs encoding the cDNA of PKG II (Ad‑PKG II), to increase the expression of PKG II, and treated with 8‑pCPT‑cGMP to activate the kinase. Western blotting was performed to detect the phosphorylation/activation of EGFR, JAK1, JAK2, STAT1 and STAT3 and the expression of cell cycle‑associated proteins, including cyclin D1 and cyclin E. EGF‑induced cell cycle changes were detected by flow cytometry. Transcriptional activity was determined by a reporter gene assay. The results demonstrated that EGF treatment increased the phosphorylation of EGFR, JAK1, JAK2, STAT1 and STAT3, increased the expression levels of cyclin D1 and cyclin E, promoted the cells to enter S phase, and stimulated transcriptional activity in the cells. Increased PKG II activity through infecting the cells with Ad‑PKG II and activating the kinase with 8‑pCPT‑cGMP efficiently reversed the changes caused by EGF. The results suggest that PKG II inhibits EGF‑induced signal transduction of the JAK/STAT‑mediated pathway and further confirms that PKG II may be a cancer inhibitor.

  10. The microRNA-132/212 family fine-tunes multiple targets in Angiotensin II signalling in cardiac fibroblasts

    DEFF Research Database (Denmark)

    Eskildsen, Tilde V; Schneider, Mikael; Sandberg, Maria B

    2015-01-01

    INTRODUCTION: MicroRNAs (miRNAs) are emerging as key regulators of cardiovascular development and disease; however, the cardiac miRNA target molecules are not well understood. We and others have described the Angiotensin II (AngII)-induced miR-132/212 family as novel regulators of cardiovascular......, signalling molecules and transcription factors. Subsequent comprehensive in silico analysis identified 24 target genes, of which 22 genes were qPCR validated. We identified seven genes involved in AngII signalling pathways. CONCLUSION: We here report novel insight of an extensive network of molecular...

  11. XIAP acts as a switch between type I and type II FAS-induced apoptosis signalling

    Science.gov (United States)

    Jost, Philipp J.; Grabow, Stephanie; Gray, Daniel; McKenzie, Mark D.; Nachbur, Ueli; Huang, David C.S.; Bouillet, Philippe; Thomas, Helen E.; Borner, Christoph; Silke, John; Strasser, Andreas; Kaufmann, Thomas

    2010-01-01

    FAS (APO-1/CD95) and its physiological ligand, FASL, regulate apoptotic death of unwanted or dangerous cells in many tissues, functioning as a guardian against autoimmunity and cancer development1-4. Distinct cell types differ in the mechanisms by which the ‘death receptor’ FAS triggers their apoptosis1-4. In type I cells, such as lymphocytes, activation of ‘effector caspases’ by FAS-induced activation of caspase-8 suffices for cell killing whereas in type II cells, including hepatocytes and pancreatic β-cells, amplification of the caspase cascade through caspase-8 mediated activation of the pro-apoptotic BCL-2 family member BID5 is essential6-8. Here we show, that loss of X-chromosome linked inhibitor of apoptosis (XIAP)9,10 function by gene-targeting or treatment with a second mitochondria-derived activator of caspases (SMAC11, also called DIABLO12: direct IAP binding protein with low pI) mimetic drug rendered hepatocytes independent of BID for FAS-induced apoptosis signalling. These results show that XIAP is the critical discriminator between type I versus type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions. PMID:19626005

  12. A Mn(II)-Mn(III) EPR signal arises from the interaction of NO with the S1 state of the water-oxidizing complex of photosystem II.

    Science.gov (United States)

    Sarrou, J; Ioannidis, N; Deligiannakis, Y; Petrouleas, V

    1998-03-17

    It was shown recently [Goussias, C., Ioannidis, N., and Petrouleas, V. (1997) Biochemistry 36, 9261-9266] that incubation of photosystem II preparations with NO at -30 degrees C in the dark results in the formation of a new intermediate of the water-oxidizing complex. This is characterized by an EPR signal centered at g = 2 with prominent manganese hyperfine structure. We have examined the detailed structure of the signal using difference EPR spectroscopy. This is facilitated by the observations that NO can be completely removed without decrease or modification of the signal, and illumination at 0 degree C eliminates the signal. The signal spans 1600 G and is characterized by sharp hyperfine structure. 14NO and 15NO cw EPR combined with pulsed ENDOR and ESEEM studies show no detectable contributions of the nitrogen nucleus to the spectrum. The spectrum bears similarities to the experimental spectrum of the Mn(II)-Mn(III) catalase [Zheng, M., Khangulov, S. V., Dismukes, G. C., and Barynin, V. V. (1994) Inorg. Chem. 33, 382-387]. Simulations allowing small variations in the catalase-tensor values result in an almost accurate reproduction of the NO-induced signal. This presents strong evidence for the assignment of the latter to a magnetically isolated Mn(II)-Mn(III) dimer. Since the starting oxidation states of Mn are higher than II, we deduce that NO acts effectively as a reductant, e.g., Mn(III)-Mn(III) + NO--> Mn(II)-Mn(III) + NO+. The temperature dependence of the nonsaturated EPR-signal intensity in the range 2-20 K indicates that the signal results from a ground state. The cw microwave power saturation data in the range 4-8 K can be interpreted assuming an Orbach relaxation mechanism with an excited state at delta = 42 K. Assuming antiferromagnetic coupling, -2JS1.S2, between the two manganese ions, J is estimated to be 10 cm-1. The finding that an EPR signal from the Mn cluster of PSII can be clearly assigned to a magnetically isolated Mn(II)-Mn(III) dimer

  13. Book Review: Sustainable Luxury and Social Entrepreneurship. Volume II: More Stories from the Pioneers

    DEFF Research Database (Denmark)

    Skjold, Else

    2017-01-01

    volume Sustainable Luxury and Social Entrepreneurship: Stories of the Pioneers, published in 2014. The book series, as well as the awards, seeks to investigate and promote the motives, context, and practical endeavours of sustainable entrepreneurs within the premium and luxury sector.......This book is based on the result of the 2016 IE Awards for Sustainability in the Premium and Luxury Sectors, hosted by IE University and IE Business School in Madrid. It is co-edited by Executive Director of the awards Eugenia Girón and President and Director of the award, Miguel Angel Gardetti......, who is also Director of the IE University Center for Studies for Sustainable Luxury. As such, it represents an overview of the content, ideas and visions of this particular event, which has been held annually since 2011 in Buenos Aires and Madrid, respectively. It succeeds the two editors’ first...

  14. RGS4 inhibits angiotensin II signaling and macrophage localization during renal reperfusion injury independent of vasospasm.

    Science.gov (United States)

    Pang, Paul; Jin, Xiaohua; Proctor, Brandon M; Farley, Michelle; Roy, Nilay; Chin, Matthew S; von Andrian, Ulrich H; Vollmann, Elisabeth; Perro, Mario; Hoffman, Ryan J; Chung, Joseph; Chauhan, Nikita; Mistri, Murti; Muslin, Anthony J; Bonventre, Joseph V; Siedlecki, Andrew M

    2015-04-01

    Vascular inflammation is a major contributor to the severity of acute kidney injury. In the context of vasospasm-independent reperfusion injury we studied the potential anti-inflammatory role of the Gα-related RGS protein, RGS4. Transgenic RGS4 mice were resistant to 25 min injury, although post-ischemic renal arteriolar diameter was equal to the wild type early after injury. A 10 min unilateral injury was performed to study reperfusion without vasospasm. Eighteen hours after injury, blood flow was decreased in the inner cortex of wild-type mice with preservation of tubular architecture. Angiotensin II levels in the kidneys of wild-type and transgenic mice were elevated in a sub-vasoconstrictive range 12 and 18 h after injury. Angiotensin II stimulated pre-glomerular vascular smooth muscle cells (VSMCs) to secrete the macrophage chemoattractant RANTES, a process decreased by angiotensin II R2 (AT2) inhibition. However, RANTES increased when RGS4 expression was suppressed implicating Gα protein activation in an AT2-RGS4-dependent pathway. RGS4 function, specific to VSMC, was tested in a conditional VSMC-specific RGS4 knockout showing high macrophage density by T2 MRI compared with transgenic and non-transgenic mice after the 10 min injury. Arteriolar diameter of this knockout was unchanged at successive time points after injury. Thus, RGS4 expression, specific to renal VSMC, inhibits angiotensin II-mediated cytokine signaling and macrophage recruitment during reperfusion, distinct from vasomotor regulation.

  15. Signals sustaining human immunoglobulin V gene hypermutation in isolated germinal centre B cells

    NARCIS (Netherlands)

    K. Dahlenborg; J.D. Pound (J.); J. Gordon (Jocelynne); C.A.K. Borrebaeck (C. A K); R. Carlsson (R.)

    2000-01-01

    textabstractAffinity maturation of antibody responses depends on somatic hypermutation of the immunoglobulin V genes. Hypermutation is initiated specifically in proliferating B cells in lymphoid germinal centres but the signals driving this process remain unknown. This study identifies signals that

  16. Addressing multi-use issues in sustainable forest management with signal-transfer modeling

    Science.gov (United States)

    Robert J. Luxmoore; William W. Hargrove; M. Lynn Tharp; W. Mac Post; Michael W. Berry; Karen S. Minser; Wendell P. Cropper; Dale W. Johnson; Boris Zeide; Ralph L. Amateis; Harold E. Burkhart; V. Clark Baldwin; Kelly D. Peterson

    2002-01-01

    Management decisions concerning impacts of projected changes in environmental and social conditions on multi-use forest products and services, such as productivity, water supply or carbon sequestration, may be facilitated with signal-transfer modeling. This simulation method utilizes a hierarchy of simulators in which the integrated responses (signals) from smaller-...

  17. ESCRT-II/Vps25 constrains digit number by endosome-mediated selective modulation of FGF-SHH signaling

    Science.gov (United States)

    Handschuh, Karen; Feenstra, Jennifer; Koss, Matthew; Ferretti, Elisabetta; Risolino, Maurizio; Zewdu, Rediet; Sahai, Michelle A.; Bénazet, Jean-Denis; Peng, Xiao P.; Depew, Michael J.; Quintana, Laura; Sharpe, James; Wang, Baolin; Alcorn, Heather; Rivi, Roberta; Butcher, Stephen; Manak, J Robert; Vaccari, Thomas; Weinstein, Harel; Anderson, Kathryn V.; Lacy, Elizabeth; Selleri, Licia

    2014-01-01

    Summary Sorting and degradation of receptors and associated signaling molecules maintain homeostasis of conserved signaling pathways during cell specification and tissue development. Yet, whether machineries that sort signaling proteins act preferentially on different receptors and ligands in different contexts remains mysterious. Here we show that Vacuolar protein sorting 25, Vps25, a component of ESCRT-II (Endosomal Sorting Complex Required for Transport II), directs preferential endosome-mediated modulation of FGF signaling in limbs. By ENU-induced mutagenesis we isolated a polydactylous mouse line carrying a hypomorphic mutation of Vps25 (Vps25ENU). Unlike Vps25-null embryos we generated, Vps25ENU/ENU mutants survive until late gestation. Their limbs display FGF signaling enhancement and consequent hyper-activation of the FGF-SHH feedback loop causing polydactyly, whereas WNT and BMP signaling remain unperturbed. Notably, Vps25ENU/ENU Mouse Embryonic Fibroblasts exhibit aberrant FGFR trafficking and degradation; however SHH signaling is unperturbed. These studies establish that the ESCRT-II machinery selectively limits FGF signaling in vertebrate skeletal patterning. PMID:25373905

  18. G-protein coupled receptor 83 (GPR83 signaling determined by constitutive and zinc(II-induced activity.

    Directory of Open Access Journals (Sweden)

    Anne Müller

    Full Text Available The G-protein coupled receptor 83 (GPR83 is an orphan G-protein coupled receptor for which the natural ligand(s and signaling pathway(s remain to be identified. Previous studies suggest a role of GPR83 in the regulation of thermogenesis and the control of circulating adiponectin. The aim of this study was to gain insights into the molecular underpinnings underlying GPR83 signaling. In particular, we aimed to assess the underlying G-protein activated signaling pathway of GPR83 and how this pathway is affected by mutational activation and zinc(II challenge. Finally, we assessed the capacity of GPR83 for homodimerization. Our results show for the first time that mouse (m GPR83 has high basal Gq/11 activity without affecting Gi or Gs signaling. Furthermore, we found that, under physiological conditions, zinc(II (but not calcium(II and magnesium(II potently activates mGPR83, thus identifying zinc(II as an endogenous molecule with agonistic capability to activate mGPR83. In line with the observation that zinc(II-ions activate mGPR83, we identified a cluster of ion-binding sensitive amino acids (e.g. His145, His204, Cys207, Glu217 in an activation sensitive receptor region of mGPR83. The occurrence of a constitutive activating mutant and a zinc(II-binding residue at the N-terminal part corroborate the importance of this region in mGPR83 signal regulation. Finally, our results indicate that mGPR83 forms homodimers, which extend the current knowledge and molecular facets of GPR83 signaling.

  19. Marine Environmental Awareness among University Students in Taiwan: A Potential Signal for Sustainability of the Oceans

    Science.gov (United States)

    Chen, Chung-Ling; Tsai, Chen-Hao

    2016-01-01

    University students are regarded as future decision-makers in society and have a high likelihood of becoming opinion-shapers in terms of the environment. Their awareness of the marine environment will therefore have a significant effect upon sustainable marine development. This study examines Taiwanese university students' marine environmental…

  20. I. Advances in NMR Signal Processing. II. Spin Dynamics in Quantum Dissipative Systems

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yung-Ya [Univ. of California, Berkeley, CA (United States)

    1998-11-01

    Part I. Advances in IVMR Signal Processing. Improvements of sensitivity and resolution are two major objects in the development of NMR/MRI. A signal enhancement method is first presented which recovers signal from noise by a judicious combination of a priordmowledge to define the desired feasible solutions and a set theoretic estimation for restoring signal properties that have been lost due to noise contamination. The effect of noise can be significantly mitigated through the process of iteratively modifying the noisy data set to the smallest degree necessary so that it possesses a collection of prescribed properties and also lies closest to the original data set. A novel detection-estimation scheme is then introduced to analyze noisy and/or strongly damped or truncated FIDs. Based on exponential modeling, the number of signals is detected based on information estimated using the matrix pencil method. theory and the spectral parameters are Part II. Spin Dynamics in body dipole-coupled systems Quantum Dissipative Systems. Spin dynamics in manyconstitutes one of the most fundamental problems in magnetic resonance and condensed-matter physics. Its many-spin nature precludes any rigorous treatment. ‘Therefore, the spin-boson model is adopted to describe in the rotating frame the influence of the dipolar local fields on a tagged spin. Based on the polaronic transform and a perturbation treatment, an analytical solution is derived, suggesting the existence of self-trapped states in the. strong coupling limit, i.e., when transverse local field >> longitudinal local field. Such nonlinear phenomena originate from the joint action of the lattice fluctuations and the reaction field. Under semiclassical approximation, it is found that the main effect of the reaction field is the renormalization of the Hamiltonian of interest. Its direct consequence is the two-step relaxation process: the spin is initially localized in a quasiequilibrium state, which is later detrapped by

  1. Tissue Architecture and Microenvironment Sustain Hormone Signaling | Center for Cancer Research

    Science.gov (United States)

    Cells interact with their environments in part through protein receptors embedded in the cell membrane. Activation of a receptor by external signaling molecules sets off a complex chain of events within the cell that can result in alterations in protein structure and function and/or changes in gene expression. Proper integration of these signals is crucial for normal cell growth and development. A more complete understanding of these normal processes will help elucidate how aberrant signaling results in diseases such as cancer.  

  2. Myosin II governs collective cell migration behaviour downstream of guidance receptor signalling.

    Science.gov (United States)

    Combedazou, Anne; Choesmel-Cadamuro, Valérie; Gay, Guillaume; Liu, Jiaying; Dupré, Loïc; Ramel, Damien; Wang, Xiaobo

    2017-01-01

    Border cell migration during Drosophila oogenesis is a potent model to study collective cell migration, a process involved in development and metastasis. Border cell clusters adopt two main types of behaviour during migration: linear and rotational. However, the molecular mechanism controlling the switch from one to the other is unknown. Here, we demonstrate that non-muscle Myosin II (NMII, also known as Spaghetti squash) activity controls the linear-to-rotational switch. Furthermore, we show that the regulation of NMII takes place downstream of guidance receptor signalling and is critical to ensure efficient collective migration. This study thus provides new insight into the molecular mechanism coordinating the different cell behaviours in a migrating cluster. © 2017. Published by The Company of Biologists Ltd.

  3. Urotensin II inhibits skeletal muscle glucose transport signaling pathways via the NADPH oxidase pathway.

    Directory of Open Access Journals (Sweden)

    Hong-Xia Wang

    Full Text Available Our previous studies have demonstrated that the urotensin (UII and its receptor are up-regulated in the skeletal muscle of mice with type II diabetes mellitus (T2DM, but the significance of UII in skeletal muscle insulin resistance remains unknown. The purpose of this study was to investigate the effect of UII on NADPH oxidase and glucose transport signaling pathways in the skeletal muscle of mice with T2DM and in C2C12 mouse myotube cells. KK/upj-AY/J mice (KK mice were divided into the following groups: KK group, with saline treatment for 2 weeks; KK+ urantide group, with daily 30 µg/kg body weight injections over the same time period of urantide, a potent urotensin II antagonist peptide; Non-diabetic C57BL/6J mice were used as normal controls. After urantide treatment, mice were subjected to an intraperitoneal glucose tolerance test, in addition to measurements of the levels of ROS, NADPH oxidase and the phosphorylated AKT, PKC and ERK. C2C12 cells were incubated with serum-free DMEM for 24 hours before conducting the experiments, and then administrated with 100 nM UII for 2 hours or 24 hours. Urantide treatment improved glucose tolerance, decreased the translocation of the NADPH subunits p40-phox and p47-phox, and increased levels of the phosphorylated PKC, AKT and ERK. In contrast, UII treatment increased ROS production and p47-phox and p67-phox translocation, and decreased the phosphorylated AKT, ERK1/2 and p38MAPK; Apocynin abrogated this effect. In conclusion, UII increased ROS production by NADPH oxidase, leading to the inhibition of signaling pathways involving glucose transport, such as AKT/PKC/ERK. Our data imply a role for UII at the molecular level in glucose homeostasis, and possibly in skeletal muscle insulin resistance in T2DM.

  4. Role of EGFR transactivation in angiotensin II signaling to extracellular regulated kinase in preglomerular smooth muscle cells.

    Science.gov (United States)

    Andresen, Bradley T; Linnoila, Jenny J; Jackson, Edwin K; Romero, Guillermo G

    2003-03-01

    Angiotensin (Ang) II promotes the phosphorylation of extracellular regulated kinase (ERK); however, the mechanisms leading to Ang II-induced ERK phosphorylation are debated. The currently accepted theory involves transactivation of epidermal growth factor receptor (EGFR). We have shown that generation of phosphatidic acid (PA) is required for the recruitment of Raf to membranes and the activation of ERK by multiple agonists, including Ang II. In the present report, we confirm that phospholipase D-dependent generation of PA is required for Ang II-mediated phosphorylation of ERK in Wistar-Kyoto and spontaneously hypertensive rat preglomerular smooth muscle cells (PGSMCs). However, EGF stimulation does not activate phospholipase D or generate PA. These observations indicate that EGF recruits Raf to membranes via a mechanism that does not involve PA, and thus, Ang II-mediated phosphorylation of ERK is partially independent of EGFR-mediated signaling cascades. We hypothesized that phosphoinositide-3-kinase (PI3K) can also act to recruit Raf to membranes; therefore, inhibition of PI3K should inhibit EGF signaling to ERK. Wortmannin, a PI3K inhibitor, inhibited EGF-mediated phosphorylation of ERK (IC50, approximately 14 nmol/L). To examine the role of the EGFR in Ang II-mediated phosphorylation of ERK we utilized 100 nmol/L wortmannin to inhibit EGFR signaling to ERK and T19N RhoA to block Ang II-mediated ERK phosphorylation. Wortmannin treatment inhibited EGF-mediated but not Ang II-mediated phosphorylation of ERK. Furthermore, T19N RhoA inhibited Ang II-mediated ERK phosphorylation, whereas T19N RhoA had significantly less effect on EGF-mediated ERK phosphorylation. We conclude that transactivation of the EGFR is not primarily responsible for Ang II-mediated activation of ERK in PGSMCs.

  5. CaMK-II activation is essential for zebrafish inner ear development and acts through Delta-Notch signaling.

    Science.gov (United States)

    Rothschild, Sarah C; Lahvic, Jamie; Francescatto, Ludmila; McLeod, Jamie J A; Burgess, Shawn M; Tombes, Robert M

    2013-09-01

    Zebrafish inner ear development is characterized by the crystallization of otoliths onto immotile kinocilia that protrude from sensory "hair" cells. The stereotypical formation of these sensory structures is dependent on the expression of key patterning genes and on Ca2+ signals. One potential target of Ca2+ signaling in the inner ear is the type II Ca2+/calmodulin-dependent protein kinase (CaMK-II), which is preferentially activated in hair cells, with intense activation at the base of kinocilia. In zebrafish, CaMK-II is encoded by seven genes; the expression of one of these genes (camk2g1) is enriched in hair cells. The suppression of camk2g1 expression by antisense morpholino oligonucleotides or inhibition of CaMK-II activation by the pharmacological antagonist, KN-93, results in aberrant otolith formation without preventing cilia formation. In fact, CaMK-II suppression results in additional ciliated hair cells and altered levels of Delta-Notch signaling members. DeltaA and deltaD transcripts are increased and DeltaD protein accumulates in hair cells of CaMK-II morphants, indicative of defective recycling and/or exocytosis. Our findings indicate that CaMK-II plays a critical role in the developing ear, influencing cell differentiation through extranuclear effects on Delta-Notch signaling. Continued expression and activation of CaMK-II in maculae and cristae in older embryos suggests continued roles in auditory sensory maturation and transduction. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Angiotensin II Type 2 Receptor Agonist Experts Sustained Neuroprotective Effects In Aged Rats

    DEFF Research Database (Denmark)

    Sumners, Colin; Isenberg, Jacob; Harmel, Allison

    2016-01-01

    in preclinical studies, effects that likely involve neurotropic actions. However, these beneficial actions of C21 have not been demonstrated to occur beyond 1 week post stroke. The objective of this study was to determine if systemic administration of C21 would exert sustained neuroprotective effects in aged...... rats. DESIGN AND METHOD: Aged adult male Sprague Dawley rats (18-20 months) underwent ischemic stroke by monofilament middle cerebral artery occlusion (MCAO) and were randomly divided into two groups that received intraperitoneal (IP) injections of either 0.9% NaCl or 0.03 mg/kg C21 at reperfusion (90...... adhesive. Infarct volume tended to be non-significantly decreased by C21 treatment at 21d post-stroke. CONCLUSIONS: These findings indicate that targeting the renin-angiotensin system, by stimulation of AT2Rs with C21, improves neurological function in aged rats with stroke over a sustained period of 21...

  7. THE HANLE AND ZEEMAN POLARIZATION SIGNALS OF THE SOLAR Ca II 8542 Å LINE

    Energy Technology Data Exchange (ETDEWEB)

    Štěpán, Jiri [Astronomical Institute ASCR, Fričova 298, 251 65 Ondřejov (Czech Republic); Bueno, Javier Trujillo [Instituto de Astrofísica de Canarias, E-38205 La Laguna, Tenerife (Spain)

    2016-07-20

    We highlight the main results of a three-dimensional (3D) multilevel radiative transfer investigation about the solar disk-center polarization of the Ca ii 8542 Å line. First, through the use of a 3D model of the solar atmosphere, we investigate the linear polarization that occurs due to the atomic level polarization produced by the absorption and scattering of anisotropic radiation, taking into account the symmetry-breaking effects caused by its thermal, dynamic, and magnetic structure. Second, we study the contribution of the Zeeman effect to the linear and circular polarization. Finally, we show examples of the Stokes profiles produced by the joint action of the atomic level polarization and the Hanle and Zeeman effects. We find that the Zeeman effect tends to dominate the linear polarization signals only in the localized patches of opposite magnetic polarity, where the magnetic field is relatively strong and slightly inclined; outside such very localized patches, the linear polarization is often dominated by the contribution of atomic level polarization. We demonstrate that a correct modeling of this last contribution requires taking into account the symmetry-breaking effects caused by the thermal, dynamic, and magnetic structure of the solar atmosphere, and that in the 3D model used the Hanle effect in forward-scattering geometry (disk-center observation) mainly reduces the polarization corresponding to the zero-field case. We emphasize that, in general, a reliable modeling of the linear polarization in the Ca ii 8542 Å line requires taking into account the joint action of atomic level polarization and the Hanle and Zeeman effects.

  8. High-resolution detection of sustained ventricular and supraventricular tachycardia through FPGA-based fuzzy processing of ECG signal.

    Science.gov (United States)

    Roy Chowdhury, Shubhajit

    2015-10-01

    The paper presents a field-programmable gate array (FPGA)-based fast processing system with 12-channel high-resolution (24 bits) front-end for ECG signal processing. The implemented high-resolution data conversion makes the system suitable for recording of late potentials of the QRS complex in patients prone to sustained ventricular tachycardia. The system accepts ECG signals through 12 channels and then filtered to minimize baseline wander and power-line interference. The filter outputs are connected to 12 delta-sigma ADCs. The whole ADCs work synchronously at 8 kHz sampling frequency, and their output data are transferred to an FPGA that computes online on the digitized sample values in real time and ascertains whether the patient under study suffers from ventricular tachycardia or not. In order to ascertain the QRS complex accurately in the noisy ECG signal, fuzzy entropy of the sample values has been computed and provided as an input to inverse multiquadratic radial basis function neural network. Using the standard CSE ECG database, the algorithm performed highly effectively. The performance of the algorithm in respect of QRS detection with sensitivity of 99.83 % and accuracy of 99.7 % is achieved when tested using single-channel ECG with entropy criteria. The performance of the QRS detection system has been compared and found to be better than most of the QRS detection systems available in the literature. Using the system, 200 patients have been diagnosed with an accuracy of 99 %.

  9. PV plasticity sustained through D1/5 dopamine signaling required for long-term memory consolidation.

    Science.gov (United States)

    Karunakaran, Smitha; Chowdhury, Ananya; Donato, Flavio; Quairiaux, Charles; Michel, Christoph M; Caroni, Pico

    2016-03-01

    Long-term consolidation of memories depends on processes occurring many hours after acquisition. Whether this involves plasticity that is specifically required for long-term consolidation remains unclear. We found that learning-induced plasticity of local parvalbumin (PV) basket cells was specifically required for long-term, but not short/intermediate-term, memory consolidation in mice. PV plasticity, which involves changes in PV and GAD67 expression and connectivity onto PV neurons, was regulated by cAMP signaling in PV neurons. Following induction, PV plasticity depended on local D1/5 dopamine receptor signaling at 0-5 h to regulate its magnitude, and at 12-14 h for its continuance, ensuring memory consolidation. D1/5 dopamine receptor activation selectively induced DARPP-32 and ERK phosphorylation in PV neurons. At 12-14 h, PV plasticity was required for enhanced sharp-wave ripple densities and c-Fos expression in pyramidal neurons. Our results reveal general network mechanisms of long-term memory consolidation that requires plasticity of PV basket cells induced after acquisition and sustained subsequently through D1/5 receptor signaling.

  10. Urotensin II induction of adult cardiomyocytes hypertrophy involves the Akt/GSK-3beta signaling pathway.

    Science.gov (United States)

    Gruson, D; Ginion, A; Decroly, N; Lause, P; Vanoverschelde, J L; Ketelslegers, J M; Bertrand, L; Thissen, J P

    2010-07-01

    Urotensin II (UII) a potent vasoactive peptide is upregulated in the failing heart and promotes cardiomyocytes hypertrophy, in particular through mitogen-activated protein kinases. However, the regulation by UII of GSK-3beta, a recognized pivotal signaling element of cardiac hypertrophy has not yet been documented. We therefore investigated in adult cardiomyocytes, if UII phosphorylates GSK-3beta and Akt, one of its upstream regulators and stabilizes beta-catenin, a GSK-3beta dependent nuclear transcriptional co-activator. Primary cultures of adult rat cardiomyocytes were stimulated for 48h with UII. Cell size and protein/DNA contents were determined. Phosphorylated and total forms of Akt, GSK-3beta and the total amount of beta-catenin were quantified by western blot. The responses of cardiomyocytes to UII were also evaluated after pretreatment with the chemical phosphatidyl-inositol-3-kinase inhibitor, LY294002, and urantide, a competitive UII receptor antagonist. UII increased cell size and the protein/DNA ratio, consistent with a hypertrophic response. UII also increased phosphorylation of Akt and its downstream target GSK-3beta. beta-Catenin protein levels were increased. All of these effects of UII were prevented by LY294002, and urantide. The UII-induced adult cardiomyocytes hypertrophy involves the Akt/GSK-3beta signaling pathways and is accompanied by the stabilization of the beta-catenin. All these effects are abolished by competitive inhibition of the UII receptor, consistent with new therapeutic perspectives for heart failure treatment. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Specific blockade by CD54 and MHC II of CD40-mediated signaling for B cell proliferation and survival

    DEFF Research Database (Denmark)

    Doyle, I S; Hollmann, C A; Crispe, I N

    2001-01-01

    Regulation of B lymphocyte proliferation is critical to maintenance of self-tolerance, and intercellular interactions are likely to signal such regulation. Here, we show that coligation of either the adhesion molecule ICAM-1/CD54 or MHC II with CD40 inhibited cell cycle progression and promoted a...

  12. Promising practices for school-located vaccination clinics-- part II: clinic operations and program sustainability.

    Science.gov (United States)

    Lott, John; Johnson, Jennifer

    2012-03-01

    A school-located mass vaccination program can enable rapid vaccination of a large number of students while minimizing disruption of their school activities. During 3 consecutive influenza seasons beginning in 2005, the Knox County Health Department conducted school-located mass vaccination clinics using live attenuated influenza vaccine. Overall, the proportion of elementary schoolchildren vaccinated with live attenuated influenza vaccine exceeded 40% each year. We describe key lessons learned in clinic operations, including obtaining informed consent, defining the organizational structure and roles, preparing the school, staffing, training, supplies, vaccine management, team communication, and data management. We conclude by discussing program costs and sustainability.

  13. Sustaining knowledge in the neutron generator community and benchmarking study. Phase II.

    Energy Technology Data Exchange (ETDEWEB)

    Huff, Tameka B.; Stubblefield, William Anthony; Cole, Benjamin Holland, II; Baldonado, Esther

    2010-08-01

    This report documents the second phase of work under the Sustainable Knowledge Management (SKM) project for the Neutron Generator organization at Sandia National Laboratories. Previous work under this project is documented in SAND2008-1777, Sustaining Knowledge in the Neutron Generator Community and Benchmarking Study. Knowledge management (KM) systems are necessary to preserve critical knowledge within organizations. A successful KM program should focus on people and the process for sharing, capturing, and applying knowledge. The Neutron Generator organization is developing KM systems to ensure knowledge is not lost. A benchmarking study involving site visits to outside industry plus additional resource research was conducted during this phase of the SKM project. The findings presented in this report are recommendations for making an SKM program successful. The recommendations are activities that promote sharing, capturing, and applying knowledge. The benchmarking effort, including the site visits to Toyota and Halliburton, provided valuable information on how the SEA KM team could incorporate a KM solution for not just the neutron generators (NG) community but the entire laboratory. The laboratory needs a KM program that allows members of the workforce to access, share, analyze, manage, and apply knowledge. KM activities, such as communities of practice (COP) and sharing best practices, provide a solution towards creating an enabling environment for KM. As more and more people leave organizations through retirement and job transfer, the need to preserve knowledge is essential. Creating an environment for the effective use of knowledge is vital to achieving the laboratory's mission.

  14. Analysis of the Human Mucosal Response to Cholera Reveals Sustained Activation of Innate Immune Signaling Pathways.

    Science.gov (United States)

    Bourque, Daniel L; Bhuiyan, Taufiqur Rahman; Genereux, Diane P; Rashu, Rasheduzzaman; Ellis, Crystal N; Chowdhury, Fahima; Khan, Ashraful I; Haq Alam, Nur; Lazina Hossain, Anik Paul; Mayo-Smith, Leslie M; Charles, Richelle C; Weil, Ana A; LaRocque, Regina C; Calderwood, Stephen B; Ryan, Edward T; Karlsson, Elinor K; Qadri, Firdausi; Harris, Jason B

    2017-11-13

    To better understand the innate immune response to Vibrio cholerae infection, we tracked gene expression in the duodenal mucosa of eleven Bangladeshi adults with cholera, using biopsies obtained immediately after rehydration and at 30 and 180 days later. We identified differentially expressed genes and performed an analysis to predict differentially regulated pathways and upstream regulators. During acute cholera, there was a broad increase in the expression of genes associated with innate immunity, including activation of the NF-κB, MAPK, and TLR-mediated signaling pathways, which unexpectedly persisted even 30 days after infection. Focusing on early differences in gene expression, we identified 37 genes that were differentially expressed on days 2 and 30 across eleven participants. These genes included the endosomal toll like receptor, TLR8, which was expressed in lamina propria cells. Underscoring a potential role for endosomal TLR-mediated signaling in vivo, our pathway analysis found that IRF7 and interferons β1 and α2 were among the top upstream regulators activated during cholera. Among innate immune effectors, we found that DUOX2, an NADPH-oxidase involved in the maintenance of intestinal homeostasis, was upregulated in intestinal epithelial cells during cholera. Notably, the observed increases in DUOX2 and TLR8 expression were also modeled in vitro when stimulating Caco-2 or THP-1 cells, respectively, with live V. cholerae but not with heat killed organisms or cholera toxin alone. These previously unidentified features of the innate immune response to V. cholerae extend our understanding mucosal immune signaling pathways and effectors activated in vivo following cholera. Copyright © 2017 American Society for Microbiology.

  15. Calmodulin-dependent Protein Kinase II/cAMP Response Element-binding Protein/Wnt/β-Catenin Signaling Cascade Regulates Angiotensin II-induced Podocyte Injury and Albuminuria*

    Science.gov (United States)

    Jiang, Lei; Xu, Lingling; Song, Yuxian; Li, Jianzhong; Mao, Junhua; Zhao, Allan Zijian; He, Weichun; Yang, Junwei; Dai, Chunsun

    2013-01-01

    Angiotensin II (Ang II) plays a pivotal role in promoting podocyte dysfunction and albuminuria, however, the underlying mechanisms have not been fully delineated. In this study, we found that Ang II induced Wnt1 expression and β-catenin nuclear translocation in cultured mouse podocytes. Blocking Wnt signaling with Dickkopf-1 (Dkk1) or β-catenin siRNA attenuated Ang II-induced podocyte injury. Ang II could also induce the phosphorylation of calmodulin-dependent protein kinase (CaMK) II and cAMP response element-binding protein (CREB) in cultured podocytes. Blockade of this pathway with CK59 or CREB siRNA could significantly inhibit Ang II-induced Wnt/β-catenin signaling and podocyte injury. In in vivo studies, administration of Ang II promoted Wnt/β-catenin signaling, aggregated podocyte damage, and albuminuria in mice. CK59 could remarkably ameliorate Ang II-induced podocyte injury and albuminuria. Furthermore, ectopic expression of exogenous Dkk1 also attenuated Ang II-induced podocytopathy in mice. Taken together, this study demonstrates that the CaMK II/CREB/Wnt/β-catenin signaling cascade plays an important role in regulating Ang II-induced podocytopathy. Targeting this signaling pathway may offer renal protection against the development of proteinuric kidney diseases. PMID:23803607

  16. The Role of Formal and Informal Forces in Shaping Consumption and Implications for Sustainable Society: Part II

    Directory of Open Access Journals (Sweden)

    Oksana Mont

    2010-08-01

    Full Text Available Looking at consumption from a societal perspective, we can see that purchasing and behavior decisions are influenced by many factors, not the least which are what the people around us and in the media are doing. Other factors include economic influences, the marketing of products and technological innovations, and regulations governing consumption. This article, Part II, argues that in order to understand consumption, we need to move beyond the dominant (economic understanding of consumers and consumer behavior, and think about the origins of our preferences, needs, and desires. A thorough understanding of consumption is informed by the contributions of sociologists, psychologists, anthropologists, and behavioral scientists, who study the socio-cultural, social, and psychological contexts in which consumer behavior is embedded. These disciplines offer rich and complex explanations of human behavior, which in turn illuminate the discussion on how consumer behavior can be made more sustainable.

  17. MnSOD upregulation sustains the Warburg effect via mitochondrial ROS and AMPK-dependent signalling in cancer.

    Science.gov (United States)

    Hart, Peter C; Mao, Mao; de Abreu, Andre Luelsdorf P; Ansenberger-Fricano, Kristine; Ekoue, Dede N; Ganini, Douglas; Kajdacsy-Balla, Andre; Diamond, Alan M; Minshall, Richard D; Consolaro, Marcia E L; Santos, Janine H; Bonini, Marcelo G

    2015-02-05

    Manganese superoxide dismutase (MnSOD/SOD2) is a mitochondria-resident enzyme that governs the types of reactive oxygen species egressing from the organelle to affect cellular signalling. Here we demonstrate that MnSOD upregulation in cancer cells establishes a steady flow of H2O2 originating from mitochondria that sustains AMP-activated kinase (AMPK) activation and the metabolic shift to glycolysis. Restricting MnSOD expression or inhibiting AMPK suppresses the metabolic switch and dampens the viability of transformed cells indicating that the MnSOD/AMPK axis is critical to support cancer cell bioenergetics. Recapitulating in vitro findings, clinical and epidemiologic analyses of MnSOD expression and AMPK activation indicated that the MnSOD/AMPK pathway is most active in advanced stage and aggressive breast cancer subtypes. Taken together, our results indicate that MnSOD serves as a biomarker of cancer progression and acts as critical regulator of tumour cell metabolism.

  18. Switching between transient and sustained signalling at the rod bipolar-AII amacrine cell synapse of the mouse retina.

    Science.gov (United States)

    Snellman, Josefin; Zenisek, David; Nawy, Scott

    2009-06-01

    At conventional synapses, invasion of an action potential into the presynaptic terminal produces a rapid Ca(2+) influx and ultimately the release of synaptic vesicles. However, retinal rod bipolar cells (RBCs) generally do not produce action potentials, and the rate of depolarization of the axon terminal is instead governed by the rate of rise of the light response, which can be quite slow. Using paired whole-cell recordings, we measured the behaviour of the RBC-AII amacrine cell synapse while simulating light-induced depolarizations either by slowly ramping the RBC voltage or by depolarizing the RBC with the mGluR6 receptor antagonist (R,S)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG). Both voltage ramps and CPPG evoked slow activation of presynaptic Ca(2+) currents and severely attenuated the early, transient component of the AII EPSC compared with voltage steps. We also found that the duration of the transient component was limited in time, and this limitation could not be explained by vesicle depletion, inhibitory feedback, or proton inhibition. Limiting the duration of the fast transient insures the availability of readily releasable vesicles to support a second, sustained component of release. The mGluR6 pathway modulator cGMP sped the rate of RBC depolarization in response to puffs of CPPG and consequently potentiated the transient component of the EPSC at the expense of the sustained component. We conclude that the rod bipolar cell is capable of both transient and sustained signalling, and modulation of the mGluR6 pathway by cGMP allows the RBC to switch between these two time courses of transmitter release.

  19. Achievements Obtained for Sustained Hypersonic Flight within the LAPCAT-II Project

    OpenAIRE

    Steelant, Johan; Varvill, Richard; Defoort, Sebastien; Hannemann, Klaus; Marini, Marco

    2015-01-01

    The design of hypersonic airbreathing vehicles is a challenging objective due to the intrinsic complexity of propulsion-airframe integration in combination with an engine cycle design able to operate over a wide Mach number range. This is one of the objectives of EC co-funded project LAPCAT-II aiming to reduce antipodal flights to less than 2 to 4 hours. Among the several studied vehicles in the preceding project LAPCAT-I, only aircraft designs for Mach 5 and 8 flights were retained in the pr...

  20. Angiotensin II Evokes Angiogenic Signals within Skeletal Muscle through Co-ordinated Effects on Skeletal Myocytes and Endothelial Cells

    Science.gov (United States)

    Gorman, Jennifer L.; Liu, Sammy T. K.; Slopack, Dara; Shariati, Khashayar; Hasanee, Adam; Olenich, Sara; Olfert, I. Mark; Haas, Tara L.

    2014-01-01

    Skeletal muscle overload induces the expression of angiogenic factors such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2, leading to new capillary growth. We found that the overload-induced increase in angiogenesis, as well as increases in VEGF, MMP-2 and MT1-MMP transcripts were abrogated in muscle VEGF KO mice, highlighting the critical role of myocyte-derived VEGF in controlling this process. The upstream mediators that contribute to overload-induced expression of VEGF have yet to be ascertained. We found that muscle overload increased angiotensinogen expression, a precursor of angiotensin (Ang) II, and that Ang II signaling played an important role in basal VEGF production in C2C12 cells. Furthermore, matrix-bound VEGF released from myoblasts induced the activation of endothelial cells, as evidenced by elevated endothelial cell phospho-p38 levels. We also found that exogenous Ang II elevates VEGF expression, as well as MMP-2 transcript levels in C2C12 myotubes. Interestingly, these responses also were observed in skeletal muscle endothelial cells in response to Ang II treatment, indicating that these cells also can respond directly to the stimulus. The involvement of Ang II in muscle overload-induced angiogenesis was assessed. We found that blockade of AT1R-dependent Ang II signaling using losartan did not attenuate capillary growth. Surprisingly, increased levels of VEGF protein were detected in overloaded muscle from losartan-treated rats. Similarly, we observed elevated VEGF production in cultured endothelial cells treated with losartan alone or in combination with Ang II. These studies conclusively establish the requirement for muscle derived VEGF in overload-induced angiogenesis and highlight a role for Ang II in basal VEGF production in skeletal muscle. However, while Ang II signaling is activated following overload and plays a role in muscle VEGF production, inhibition of this pathway is not sufficient to halt overload

  1. Gestational exposure to elevated testosterone levels induces hypertension via heightened vascular angiotensin II type 1 receptor signaling in rats.

    Science.gov (United States)

    Chinnathambi, Vijayakumar; More, Amar S; Hankins, Gary D; Yallampalli, Chandra; Sathishkumar, Kunju

    2014-07-01

    Pre-eclampsia is a life-threatening pregnancy disorder whose pathogenesis remains unclear. Plasma testosterone levels are elevated in pregnant women with pre-eclampsia and polycystic ovary syndrome, who often develop gestational hypertension. We tested the hypothesis that increased gestational testosterone levels induce hypertension via heightened angiotensin II signaling. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate from Gestational Day 15 to 19 to induce a 2-fold increase in plasma testosterone levels, similar to levels observed in clinical conditions like pre-eclampsia. A subset of rats in these two groups was given losartan, an angiotensin II type 1 receptor antagonist by gavage during the course of testosterone exposure. Blood pressure levels were assessed through a carotid arterial catheter and endothelium-independent vascular reactivity through wire myography. Angiotensin II levels in plasma and angiotensin II type 1 receptor expression in mesenteric arteries were also examined. Blood pressure levels were significantly higher on Gestational Day 20 in testosterone-treated dams than in controls. Treatment with losartan during the course of testosterone exposure significantly attenuated testosterone-induced hypertension. Plasma angiotensin II levels were not significantly different between control and testosterone-treated rats; however, elevated testosterone levels significantly increased angiotensin II type 1 receptor protein levels in the mesenteric arteries. In testosterone-treated rats, mesenteric artery contractile responses to angiotensin II were significantly greater, whereas contractile responses to K(+) depolarization and phenylephrine were unaffected. The results demonstrate that elevated testosterone during gestation induces hypertension in pregnant rats via heightened angiotensin II type 1 receptor-mediated signaling, providing a molecular mechanism linking elevated maternal testosterone levels with gestational

  2. Lipid rafts are required for signal transduction by angiotensin II receptor type 1 in neonatal glomerular mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Adebiyi, Adebowale, E-mail: aadebiyi@uthsc.edu; Soni, Hitesh; John, Theresa A.; Yang, Fen

    2014-05-15

    Angiotensin II (ANG-II) receptors (AGTRs) contribute to renal physiology and pathophysiology, but the underlying mechanisms that regulate AGTR function in glomerular mesangium are poorly understood. Here, we show that AGTR1 is the functional AGTR subtype expressed in neonatal pig glomerular mesangial cells (GMCs). Cyclodextrin (CDX)-mediated cholesterol depletion attenuated cell surface AGTR1 protein expression and ANG-II-induced intracellular Ca{sup 2+} ([Ca{sup 2+}]{sub i}) elevation in the cells. The COOH-terminus of porcine AGTR1 contains a caveolin (CAV)-binding motif. However, neonatal GMCs express CAV-1, but not CAV-2 and CAV-3. Colocalization and in situ proximity ligation assay detected an association between endogenous AGTR1 and CAV-1 in the cells. A synthetic peptide corresponding to the CAV-1 scaffolding domain (CSD) sequence also reduced ANG-II-induced [Ca{sup 2+}]{sub i} elevation in the cells. Real-time imaging of cell growth revealed that ANG-II stimulates neonatal GMC proliferation. ANG-II-induced GMC growth was attenuated by EMD 66684, an AGTR1 antagonist; BAPTA, a [Ca{sup 2+}]{sub i} chelator; KN-93, a Ca{sup 2+}/calmodulin-dependent protein kinase II inhibitor; CDX; and a CSD peptide, but not PD 123319, a selective AGTR2 antagonist. Collectively, our data demonstrate [Ca{sup 2+}]{sub i}-dependent proliferative effect of ANG-II and highlight a critical role for lipid raft microdomains in AGTR1-mediated signal transduction in neonatal GMCs. - Highlights: • AGTR1 is the functional AGTR subtype expressed in neonatal mesangial cells. • Endogenous AGTR1 associates with CAV-1 in neonatal mesangial cells. • Lipid raft disruption attenuates cell surface AGTR1 protein expression. • Lipid raft disruption reduces ANG-II-induced [Ca{sup 2+}]{sub i} elevation in neonatal mesangial cells. • Lipid raft disruption inhibits ANG-II-induced neonatal mesangial cell growth.

  3. Angiotensin-II-induced Muscle Wasting is Mediated by 25-Hydroxycholesterol via GSK3β Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Congcong Shen

    2017-02-01

    Full Text Available While angiotensin II (ang II has been implicated in the pathogenesis of cardiac cachexia (CC, the molecules that mediate ang II's wasting effect have not been identified. It is known TNF-α level is increased in patients with CC, and TNF-α release is triggered by ang II. We therefore hypothesized that ang II induced muscle wasting is mediated by TNF-α. Ang II infusion led to skeletal muscle wasting in wild type (WT but not in TNF alpha type 1 receptor knockout (TNFR1KO mice, suggesting that ang II induced muscle loss is mediated by TNF-α through its type 1 receptor. Microarray analysis identified cholesterol 25-hydroxylase (Ch25h as the down stream target of TNF-α. Intraperitoneal injection of 25-hydroxycholesterol (25-OHC, the product of Ch25h, resulted in muscle loss in C57BL/6 mice, accompanied by increased expression of atrogin-1, MuRF1 and suppression of IGF-1/Akt signaling pathway. The identification of 25-OHC as an inducer of muscle wasting has implications for the development of specific treatment strategies in preventing muscle loss.

  4. Activation of Aurora A kinase through the FGF1/FGFR signaling axis sustains the stem cell characteristics of glioblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Yi-Chao [Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan (China); Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan (China); Kao, Chien-Yu [Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan (China); Graduate Program of Biotechnology in Medicine, Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan (China); Chung, Yu-Fen; Lee, Don-Ching [Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan (China); Liu, Jen-Wei [Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan (China); Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan (China); Chiu, Ing-Ming, E-mail: ingming@nhri.org.tw [Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan (China); Graduate Program of Biotechnology in Medicine, Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan (China); Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan (China)

    2016-06-10

    Fibroblast growth factor 1 (FGF1) binds and activates FGF receptors, thereby regulating cell proliferation and neurogenesis. Human FGF1 gene 1B promoter (−540 to +31)-driven SV40 T antigen has been shown to result in tumorigenesis in the brains of transgenic mice. FGF1B promoter (−540 to +31)-driven green fluorescent protein (F1BGFP) has also been used in isolating neural stem cells (NSCs) with self-renewal and multipotency from developing and adult mouse brains. In this study, we provide six lines of evidence to demonstrate that FGF1/FGFR signaling is implicated in the expression of Aurora A (AurA) and the activation of its kinase domain (Thr288 phosphorylation) in the maintenance of glioblastoma (GBM) cells and NSCs. First, treatment of FGF1 increases AurA expression in human GBM cell lines. Second, using fluorescence-activated cell sorting, we observed that F1BGFP reporter facilitates the isolation of F1BGFP(+) GBM cells with higher expression levels of FGFR and AurA. Third, both FGFR inhibitor (SU5402) and AurA inhibitor (VX680) could down-regulate F1BGFP-dependent AurA activity. Fourth, inhibition of AurA activity by two different AurA inhibitors (VX680 and valproic acid) not only reduced neurosphere formation but also induced neuronal differentiation of F1BGFP(+) GBM cells. Fifth, flow cytometric analyses demonstrated that F1BGFP(+) GBM cells possessed different NSC cell surface markers. Finally, inhibition of AurA by VX680 reduced the neurosphere formation of different types of NSCs. Our results show that activation of AurA kinase through FGF1/FGFR signaling axis sustains the stem cell characteristics of GBM cells. Implications: This study identified a novel mechanism for the malignancy of GBM, which could be a potential therapeutic target for GBM. - Highlights: • We report that FGF1 treatment can stimulate AurA kinase expression in human GBM cells. • FGF1/FGFR signaling is involved in the activation of AurA kinase. • FGF1 sustains the self

  5. From rainfed agriculture to stress-avoidance irrigation: II. Sustainability, crop yield, and profitability

    Science.gov (United States)

    Vico, Giulia; Porporato, Amilcare

    2011-02-01

    The optimality of irrigation strategies may be sought with respect to a number of criteria, including water requirements, crop yield, and profitability. To explore the suitability of different demand-based irrigation strategies, we link the probabilistic description of irrigation requirements under stochastic hydro-climatic conditions, provided in a companion paper [Vico G, Porporato A. From rainfed agriculture to stress-avoidance irrigation: I. A generalized irrigation scheme with stochastic soil moisture. Adv Water Resour 2011;34(2):263-71], to crop-yield and economic analyses. Water requirements, application efficiency, and investment costs of different irrigation methods, such as surface, sprinkler and drip irrigation systems, are described via a unified conceptual and theoretical approach, which includes rainfed agriculture and stress-avoidance irrigation as extreme cases. This allows us to analyze irrigation strategies with respect to sustainability, productivity, and economic return, using the same framework, and quantify them as a function of climate, crop, and soil parameters. We apply our results to corn ( Zea mays), a food staple and biofuel source, which is currently mainly irrigated through surface systems. As our analysis shows, micro-irrigation maximizes water productivity, but more traditional solutions may be more profitable at least in some contexts.

  6. Carbonic anhydrase II regulates differentiation of ameloblasts via intracellular pH-dependent JNK signaling pathway.

    Science.gov (United States)

    Wang, Xiaogu; Suzawa, Tetsuo; Ohtsuka, Hirotada; Zhao, Baohong; Miyamoto, Yoichi; Miyauchi, Tomohiko; Nishimura, Riko; Inoue, Tomio; Nakamura, Masanori; Baba, Kazuyoshi; Kamijo, Ryutaro

    2010-11-01

    Differentiation of ameloblasts from undifferentiated epithelial cells is controlled by diverse growth factors, as well as interactions between epithelium and mesenchyme. However, there is a considerable lack of knowledge regarding the precise mechanisms that control ameloblast differentiation and enamel biomineralization. We found that the expression level of carbonic anhydrase II (CAII) is strongly up-regulated in parallel with differentiation of enamel epithelium tissues, while the enzyme activity of CA was also increased along with differentiation in ameloblast primary cultures. The expression level of amelogenin, a marker of secretory-stage ameloblasts, was enhanced by ethoxzolamide (EZA), a CA inhibitor, as well as CAII antisense (CAIIAS), whereas the expression of enamel matrix serine proteinase-1 (EMSP-1), a marker for maturation-stage ameloblasts, was suppressed by both. These agents also promoted ameloblast proliferation. In addition, inhibition of ameloblast differentiation by EZA and CAIIAS was confirmed using tooth germ organ cultures. Furthermore, EZA and CAIIAS elevated intracellular pH in ameloblasts, while experimental decreases in intracellular pH abolished the effect of CAIIAS on ameloblasts and triggered the activation of c-Jun N-terminal kinase (JNK). SP600125, a JNK inhibitor, abrogated the response of ameloblasts to an experimental decrease in intracellular pH, while the inhibition of JNK also impaired ameloblast differentiation. These results suggest a novel role for CAII during amelogenesis, that is, controlling the differentiation of ameloblasts. Regulation of intracellular pH, followed by activation of the JNK signaling pathway, may be responsible for the effects of CAII on ameloblasts. © 2010 Wiley-Liss, Inc.

  7. Mesenchymal stem cells from osteoporotic patients feature impaired signal transduction but sustained osteoinduction in response to BMP-2 stimulation.

    Science.gov (United States)

    Prall, Wolf Christian; Haasters, Florian; Heggebö, Jostein; Polzer, Hans; Schwarz, Christina; Gassner, Christoph; Grote, Stefan; Anz, David; Jäger, Marcus; Mutschler, Wolf; Schieker, Matthias

    2013-11-01

    Osteoporotic fractures show reduced callus formation and delayed bone healing. Cellular sources of fracture healing are mesenchymal stem cells (MSC) that differentiate into osteoblasts by stimulation with osteoinductive cytokines, such as BMP-2. We hypothesized that impaired signal transduction and reduced osteogenic differentiation capacity in response to BMP-2 may underlie the delayed fracture healing. Therefore, MSC were isolated from femoral heads of healthy and osteoporotic patients. Grouping was carried out by bone mineral densitometry in an age-matched manner. MSC were stimulated with BMP-2. Signal transduction was assessed by western blotting of pSMAD1/5/8 and pERK1/2 as well as by quantitative RT-PCR of Runx-2, Dlx5, and Osteocalcin. Osteogenic differentiation was assessed by quantifying Alizarin Red staining. Osteoporotic MSC featured an accurate phosphorylation pattern of SMAD1/5/8 but a significantly reduced activation of ERK1/2 by BMP-2 stimulation. Furthermore, osteoporotic MSC showed significantly reduced basal expression levels of Runx-2 and Dlx5. However, Runx-2, Dlx5, and Osteocalcin expression showed adequate up-regulation due to BMP-2 stimulation. The global osteogenic differentiation in standard osteogenic differentiation media was reduced in osteoporotic MSC. Nevertheless, osteoporotic MSC were shown to feature an adequate induction of osteogenic differentiation due to BMP-2 stimulation. Taken together, we here demonstrate osteoporosis associated alterations in BMP-2 signaling but sustained specific osteogenic differentiation capacity in response to BMP-2. Therefore, BMP-2 may represent a promising therapeutic agent for the treatment of fractures in osteoporotic patients. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Simulation of the S2 state multiline electron paramagnetic resonance signal of photosystem II: a multifrequency approach.

    OpenAIRE

    Ahrling, K A; Pace, R J

    1995-01-01

    The S2 state electron paramagnetic resonance (EPR) multiline signal of Photosystem II has been simulated at Q-band (35 Ghz), X-band (9 GHz) and S-band (4 GHz) frequencies. The model used for the simulation assumes that the signal arises from an essentially magnetically isolated MnIII-MnIV dimer, with a ground state electronic spin ST = 1/2. The spectra are generated from exact numerical solution of a general spin Hamiltonian containing anisotropic hyperfine and quadrupolar interactions at bot...

  9. Sustainability of Hydrogen Supply Chain. Part II: Prioritizing and Classifying the Sustainability of Hydrogen Supply Chains based on the Combination of Extension Theory and AHP

    DEFF Research Database (Denmark)

    Ren, Jingzheng; Manzardo, Alessandro; Toniolo, Sara

    2013-01-01

    The purpose of this study is to develop a method for prioritizing and classifying the sustainability of hydrogen supply chains and assist decision-making for the stakeholders/decision-makers. Multiple criteria for sustainability assessment of hydrogen supply chains are considered and multiple...... decision-makers are allowed to participate in the decision-making using linguistic terms. In this study, extension theory and analytic hierarchy process are combined to rate the sustainability of hydrogen supply chains. The sustainability of hydrogen supply chains could be identified according...

  10. The microRNA-132/212 family fine-tunes multiple targets in Angiotensin II signalling in cardiac fibroblasts

    DEFF Research Database (Denmark)

    Eskildsen, Tilde V; Schneider, Mikael; Sandberg, Maria B

    2015-01-01

    function including regulation of cardiac hypertrophy, heart failure and blood pressure possibly through AT1R signalling. However, the miR-132/212 targets in the heart remain unknown. MATERIALS AND METHODS: To understand the role of these miRNAs in cardiac signalling networks, we undertook comprehensive......INTRODUCTION: MicroRNAs (miRNAs) are emerging as key regulators of cardiovascular development and disease; however, the cardiac miRNA target molecules are not well understood. We and others have described the Angiotensin II (AngII)-induced miR-132/212 family as novel regulators of cardiovascular...... in silico and in vitro experiments to identify miR-132/212 molecular targets in primary rat cardiac fibroblasts. RESULTS: MiR-132/212 overexpression increased fibroblast cell size and mRNA arrays detected several hundred genes that were differentially expressed, including a wide panel of receptors...

  11. HDAC6 contributes to pathological responses of heart and skeletal muscle to chronic angiotensin-II signaling.

    Science.gov (United States)

    Demos-Davies, Kimberly M; Ferguson, Bradley S; Cavasin, Maria A; Mahaffey, Jennifer H; Williams, Sarah M; Spiltoir, Jessica I; Schuetze, Katherine B; Horn, Todd R; Chen, Bo; Ferrara, Claudia; Scellini, Beatrice; Piroddi, Nicoletta; Tesi, Chiara; Poggesi, Corrado; Jeong, Mark Y; McKinsey, Timothy A

    2014-07-15

    Little is known about the function of the cytoplasmic histone deacetylase HDAC6 in striated muscle. Here, we addressed the role of HDAC6 in cardiac and skeletal muscle remodeling induced by the peptide hormone angiotensin II (ANG II), which plays a central role in blood pressure control, heart failure, and associated skeletal muscle wasting. Comparable with wild-type (WT) mice, HDAC6 null mice developed cardiac hypertrophy and fibrosis in response to ANG II. However, whereas WT mice developed systolic dysfunction upon treatment with ANG II, cardiac function was maintained in HDAC6 null mice treated with ANG II for up to 8 wk. The cardioprotective effect of HDAC6 deletion was mimicked in WT mice treated with the small molecule HDAC6 inhibitor tubastatin A. HDAC6 null mice also exhibited improved left ventricular function in the setting of pressure overload mediated by transverse aortic constriction. HDAC6 inhibition appeared to preserve systolic function, in part, by enhancing cooperativity of myofibrillar force generation. Finally, we show that HDAC6 null mice are resistant to skeletal muscle wasting mediated by chronic ANG-II signaling. These findings define novel roles for HDAC6 in striated muscle and suggest potential for HDAC6-selective inhibitors for the treatment of cardiac dysfunction and muscle wasting in patients with heart failure. Copyright © 2014 the American Physiological Society.

  12. Quartz crystal microbalance aptasensor for sensitive detection of mercury(II) based on signal amplification with gold nanoparticles.

    Science.gov (United States)

    Dong, Zong-Mu; Zhao, Guang-Chao

    2012-01-01

    We show that a short mercury-specific aptamer (MSA) along with gold nanoparticles (Au-NPs) can be used to determine Hg(II) ion by a combination of a QCM-based sensor and a flow system. The MSA binds specifically to Hg(II), and the Au-NPs can amplify the signal to enhance sensitivity. Specifically, the short thiolated MSAs are immobilized on the surface of the QCM as the capture probe, and the MSAs are linked to the Au-NPs as the linking probe. The two components can form a sandwich structure of the T-Hg(II)-T type in the presence of Hg(II) ions. This leads to change in the mass on the QCM and a change in the resonance frequency. Hg(II) can be determined with a detection limit of 0.24 ± 0.06 nM which is better by three orders of magnitude than previous methods. The sensor can be regenerated by disrupting the T-Hg(II)-T base pairs with a solution of cysteine.

  13. Candesartan ameliorates arsenic-induced hypertensive vascular remodeling by regularizing angiotensin II and TGF-beta signaling in rats.

    Science.gov (United States)

    Khuman, Maibam Wanta; Harikumar, Sankaran Kutty; Sadam, Abdul; Kesavan, Manickam; Susanth, Vattaparambil Sukumaran; Parida, Subhashree; Singh, Karam Pal; Sarkar, Souvendra Nath

    2016-12-30

    Arsenic exposure can cause several cardiovascular diseases, including hypertension, atherosclerosis and microvascular disease. Earlier, we reported that arsenic-mediated enhancement of angiotensin II (AngII) signaling can impair vascular physiology. Here, we investigated whether the AT1 receptor (AT1R) blocker candesartan can ameliorate the arsenic-induced hypertensive vascular remodeling in rats and whether the amelioration could relate to attenuation in vascular AngII and TGF-β signaling. Rats were exposed to sodium arsenite (50ppm) through drinking water for 90 consecutive days. Candesartan (1mg/kg bw, orally) was administered once daily during the last 30days of arsenic exposure. Non-invasive blood pressure was recorded weekly in conscious rats, while AngII-induced change in mean arterial pressure in anaesthetized rats was measured by invasive method on the 91st day. On this day, blood was collected from other animals for measuring AngII level. Western blot of AT1, AT2 and TβRII receptors; ELISA of PTK, RasGAP, ERK-1/2, TGF-β and CTGF; immunohistochemistry of phosphorylated Smad3, Smad4 and collagen III, hydroxyproline/total collagen estimation, collagen deposition by Masson's trichrome staining and histomorphometry were carried out in thoracic aorta. Arsenic increased non-invasive systolic, diastolic and mean arterial pressure. Further, AngII caused concentration-dependent incremental change in mean arterial pressure in the arsenic-exposed rats. Arsenic upregulated AT1 and TβRII receptor proteins; elevated the levels of PTK, ERK-1/2, TGF-β and CTGF, decreased RasGAP level and augmented the immunoreactivities of Smad3, Smad4 and collagen III. Arsenic also increased hydroxyproline/total collagen level, proliferation of collagen fibres and thickness of aortic wall and collagenous adventitia. Candesartan normalized blood pressure, regularized receptor expressions, MAP kinase and TGF-β signaling, restored collagen deposition and regressed aortic thickness

  14. Design and Implementation of Digital Chebyshev Type II Filter using XSG for Noise Reduction in ECG Signal

    OpenAIRE

    Kaustubh Gaikwad; Mahesh Chavan

    2016-01-01

    ASIC Chips and Digital Signal Processors are generally used for implementing digital filters. Now days the advanced technologies lead to use of field programmable Gate Array (FPGA) for the implementation of Digital Filters.The present paper deals with Design and Implementation of Digital IIR Chebyshev type II filter using Xilinx System Generator. The Quantization and Overflow are main crucial parameters while designing the filter on FPGA and that need to be consider for getting th...

  15. A signal processing approach for enriched region detection in RNA polymerase II ChIP-seq data.

    Science.gov (United States)

    Han, Zhi; Tian, Lu; Pécot, Thierry; Huang, Tim; Machiraju, Raghu; Huang, Kun

    2012-03-13

    RNA polymerase II (PolII) is essential in gene transcription and ChIP-seq experiments have been used to study PolII binding patterns over the entire genome. However, since PolII enriched regions in the genome can be very long, existing peak finding algorithms for ChIP-seq data are not adequate for identifying such long regions. Here we propose an enriched region detection method for ChIP-seq data to identify long enriched regions by combining a signal denoising algorithm with a false discovery rate (FDR) approach. The binned ChIP-seq data for PolII are first processed using a non-local means (NL-means) algorithm for purposes of denoising. Then, a FDR approach is developed to determine the threshold for marking enriched regions in the binned histogram. We first test our method using a public PolII ChIP-seq dataset and compare our results with published results obtained using the published algorithm HPeak. Our results show a high consistency with the published results (80-100%). Then, we apply our proposed method on PolII ChIP-seq data generated in our own study on the effects of hormone on the breast cancer cell line MCF7. The results demonstrate that our method can effectively identify long enriched regions in ChIP-seq datasets. Specifically, pertaining to MCF7 control samples we identified 5,911 segments with length of at least 4 Kbp (maximum 233,000 bp); and in MCF7 treated with E2 samples, we identified 6,200 such segments (maximum 325,000 bp). We demonstrated the effectiveness of this method in studying binding patterns of PolII in cancer cells which enables further deep analysis in transcription regulation and epigenetics. Our method complements existing peak detection algorithms for ChIP-seq experiments.

  16. Angiotensin II type 1 receptor signalling regulates microRNA differentially in cardiac fibroblasts and myocytes

    DEFF Research Database (Denmark)

    Jeppesen, Pia Lindgren; Christensen, Gitte Lund; Schneider, Mikael

    2011-01-01

    and -independent pathways. MiRNA regulation was verified with quantitative PCR in both HEK293N cells and primary cardiac myocytes and fibroblasts. Key results: Our studies revealed five miRNAs (miR-29b, -129-3p, -132, -132* and -212) that were upregulated by Ang II in HEK293N cells. In contrast, the biased Ang II...... in primary cultures of adult cardiac fibroblasts. Interestingly, Ang II did not regulate miRNA expression in cardiac myocytes, but SII Ang II significantly downregulated miR-129-3p. Conclusions and implications: Five miRNAs were regulated by Ang II through mechanisms depending on Gaq/11 and Erk1/2 activation...

  17. Signal transduction by HLA class II antigens expressed on activated T cells

    DEFF Research Database (Denmark)

    Ødum, Niels; Martin, P J; Schieven, G L

    1991-01-01

    Human T cells express HLA class II antigens upon activation. Although activated, class II+ T cells can present alloantigens under certain circumstances, the functional role of class II antigens on activated T cells remains largely unknown. Here, we report that cross-linking of HLA-DR molecules...... after cross-linking CD4. Ligation of CD4 and class II molecules generated a synergistic effect of the intracellular free Ca2+ concentration response that required an interaction between the molecules on the cell surface. Since class II is the natural ligand for CD4, the present data suggest that class...... expressed on allospecific, CD4+ T clones and cell lines can function as transduction elements that trigger rapid cellular responses including tyrosine phosphorylation of cellular proteins and mobilization of Ca2+ from internal stores. The proteins phosphorylated on tyrosine were distinct from those observed...

  18. Sustained Submicromolar H2O2 Levels Induce Hepcidin via Signal Transducer and Activator of Transcription 3 (STAT3)*

    Science.gov (United States)

    Millonig, Gunda; Ganzleben, Ingo; Peccerella, Teresa; Casanovas, Guillem; Brodziak-Jarosz, Lidia; Breitkopf-Heinlein, Katja; Dick, Tobias P.; Seitz, Helmut-Karl; Muckenthaler, Martina U.; Mueller, Sebastian

    2012-01-01

    The peptide hormone hepcidin regulates mammalian iron homeostasis by blocking ferroportin-mediated iron export from macrophages and the duodenum. During inflammation, hepcidin is strongly induced by interleukin 6, eventually leading to the anemia of chronic disease. Here we show that hepatoma cells and primary hepatocytes strongly up-regulate hepcidin when exposed to low concentrations of H2O2 (0.3–6 μm), concentrations that are comparable with levels of H2O2 released by inflammatory cells. In contrast, bolus treatment of H2O2 has no effect at low concentrations and even suppresses hepcidin at concentrations of >50 μm. H2O2 treatment synergistically stimulates hepcidin promoter activity in combination with recombinant interleukin-6 or bone morphogenetic protein-6 and in a manner that requires a functional STAT3-responsive element. The H2O2-mediated hepcidin induction requires STAT3 phosphorylation and is effectively blocked by siRNA-mediated STAT3 silencing, overexpression of SOCS3 (suppressor of cytokine signaling 3), and antioxidants such as N-acetylcysteine. Glycoprotein 130 (gp130) is required for H2O2 responsiveness, and Janus kinase 1 (JAK1) is required for adequate basal signaling, whereas Janus kinase 2 (JAK2) is dispensable upstream of STAT3. Importantly, hepcidin levels are also increased by intracellular H2O2 released from the respiratory chain in the presence of rotenone or antimycin A. Our results suggest a novel mechanism of hepcidin regulation by nanomolar levels of sustained H2O2. Thus, similar to cytokines, H2O2 provides an important regulatory link between inflammation and iron metabolism. PMID:22932892

  19. The duality of gaze: Eyes extract and signal social information during sustained cooperative and competitive dyadic gaze

    Directory of Open Access Journals (Sweden)

    Michelle eJarick

    2015-09-01

    Full Text Available In contrast to nonhuman primate eyes, which have a dark sclera surrounding a dark iris, human eyes have a white sclera that surrounds a dark iris. This high contrast morphology allows humans to determine quickly and easily where others are looking and infer what they are attending to. In recent years an enormous body of work has used photos and schematic images of faces to study these aspects of social attention, e.g., the selection of the eyes of others and the shift of attention to where those eyes are directed. However, evolutionary theory holds that humans did not develop a high contrast morphology simply to use the eyes of others as attentional cues; rather they sacrificed camouflage for communication, that is, to signal their thoughts and intentions to others. In the present study we demonstrate the importance of this by taking as our starting point the hypothesis that a cornerstone of nonverbal communication is the eye contact between individuals and the time that it is held. In a single simple study we show experimentally that the effect of eye contact can be quickly and profoundly altered merely by having participants, who had never met before, play a game in a cooperative or competitive manner. After the game participants were asked to make eye contact for a prolonged period of time (10 minutes. Those who had played the game cooperatively found this terribly difficult to do, repeatedly talking and breaking gaze. In contrast, those who had played the game competitively were able to stare quietly at each other for a sustained period. Collectively these data demonstrate that when looking at the eyes of a real person one both acquires and signals information to the other person. This duality of gaze is critical to nonverbal communication, with the nature of that communication shaped by the relationship between individuals, e.g., cooperative or competitive.

  20. Apical constriction and invagination downstream of the canonical Wnt signaling pathway require Rho1 and Myosin II.

    Science.gov (United States)

    Zimmerman, Sandra G; Thorpe, Lauren M; Medrano, Vilma R; Mallozzi, Carolyn A; McCartney, Brooke M

    2010-04-01

    The tumor suppressor Adenomatous polyposis coli (APC) is a negative regulator of Wnt signaling and functions in cytoskeletal organization. Disruption of human APC in colonic epithelia initiates benign polyps that progress to carcinoma following additional mutations. The early events of polyposis are poorly understood, as is the role of canonical Wnt signaling in normal epithelial architecture and morphogenesis. To determine the consequences of complete loss of APC in a model epithelium, we generated APC2 APC1 double null clones in the Drosophila wing imaginal disc. APC loss leads to segregation, apical constriction, and invagination that result from transcriptional activation of canonical Wnt signaling. Further, we show that Wnt-dependent changes in cell fate can be decoupled from Wnt-dependent changes in cell shape. Wnt activation is reported to upregulate DE-cadherin in wing discs, and elevated DE-cadherin is thought to promote apical constriction. We find that apical constriction and invagination of APC null tissue are independent of DE-cadherin elevation, but are dependent on Myosin II activity. Further, we show that disruption of Rho1 suppresses apical constriction and invagination in APC null cells. Our data suggest a novel link between canonical Wnt signaling and epithelial structure that requires activation of the Rho1 pathway and Myosin II. Copyright 2010 Elsevier Inc. All rights reserved.

  1. Apical constriction and invagination downstream of the canonical Wnt signaling pathway requires Rho1 and Myosin II

    Science.gov (United States)

    Zimmerman, Sandra G.; Thorpe, Lauren M.; Medrano, Vilma R.; Mallozzi, Carolyn A.; McCartney, Brooke M.

    2010-01-01

    The tumor suppressor Adenomatous polyposis coli (APC) is a negative regulator of Wnt signaling and functions in cytoskeletal organization. Disruption of human APC in colonic epithelia initiates benign polyps that progress to carcinoma following additional mutations. The early events of polyposis are poorly understood, as is the role of canonical Wnt signaling in normal epithelial architecture and morphogenesis. To determine the consequences of complete loss of APC in a model epithelium, we generated APC2 APC1 double null clones in the Drosophila wing imaginal disc. APC loss leads to segregation, apical constriction, and invagination that result from transcriptional activation of canonical Wnt signaling. Further, we show that Wnt-dependent changes in cell fate can be decoupled from Wnt-dependent changes in cell shape. Wnt activation is reported to upregulate DE-cadherin in wing discs, and elevated DE-cadherin is thought to promote apical constriction. We find that apical constriction and invagination of APC null tissue are independent of DE-cadherin elevation, but are dependent on Myosin II activity. Further, we show that disruption of Rho1 suppresses apical constriction and invagination in APC null cells. Our data suggest a novel link between canonical Wnt signaling and epithelial structure that requires activation of the Rho1 pathway and Myosin II. PMID:20102708

  2. Enhancement by Copper(II) of the voltammetric signal of vitamin B2 applied to its determination in breakfast cereals.

    Science.gov (United States)

    Kadara, Rashid O; Fogg, Arnold G; Haggett, Barry G D; Birch, Brian J

    2009-02-11

    Addition of copper(II) to breakfast cereal samples was shown to significantly enhance the analytical signal obtained by electrochemical reduction of vitamin B(2) using linear sweep voltammetry on disposable carbon electrodes. The enhancement was observed only when dissolved oxygen was present. In model solutions the analytical signal was linear in the concentration range 6-150 ng/mL with a calculated limit of detection of 5 ng/mL (S/N = 3). This compared favorably with earlier work using a similar measurement approach--but in the absence of copper--in which the limit of detection was calculated to be 900 ng/mL. The effects of potential interferents commonly found in cereals were examined. In addition to signal attenuation by both sugar and starch (already reported), folic acid was found to increase (+6%) and iron to decrease (-11%) the analytical signal when present in the maximum concentration ratios, with respect to vitamin B(2), that are normally found in breakfast cereals. Nevertheless, the simplicity of the approach was potentially attractive for near-line quality control applications in manufacturing. The utility of the measurement approach was demonstrated by the addition of excess copper(II) sulfate to determine vitamin B(2) in aqueous extracts of breakfast cereals. The results agreed well with those provided by the cereal manufacturer who used an established HPLC method.

  3. Activation of ERα signaling differentially modulates IFN-γ induced HLA-class II expression in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Ahmed A Mostafa

    Full Text Available The coordinate regulation of HLA class II (HLA-II is controlled by the class II transactivator, CIITA, and is crucial for the development of anti-tumor immunity. HLA-II in breast carcinoma is associated with increased IFN-γ levels, reduced expression of the estrogen receptor (ER and reduced age at diagnosis. Here, we tested the hypothesis that estradiol (E₂ and ERα signaling contribute to the regulation of IFN-γ inducible HLA-II in breast cancer cells. Using a panel of established ER⁻ and ER⁺ breast cancer cell lines, we showed that E₂ attenuated HLA-DR in two ER⁺ lines (MCF-7 and BT-474, but not in T47D, while it augmented expression in ER⁻ lines, SK-BR-3 and MDA-MB-231. To further study the mechanism(s, we used paired transfectants: ERα⁺ MC2 (MDA-MB-231 c10A transfected with the wild type ERα gene and ERα⁻ VC5 (MDA-MB-231 c10A transfected with the empty vector, treated or not with E₂ and IFN-γ. HLA-II and CIITA were severely reduced in MC2 compared to VC5 and were further exacerbated by E₂ treatment. Reduced expression occurred at the level of the IFN-γ inducible CIITA promoter IV. The anti-estrogen ICI 182,780 and gene silencing with ESR1 siRNA reversed the E2 inhibitory effects, signifying an antagonistic role for activated ERα on CIITA pIV activity. Moreover, STAT1 signaling, necessary for CIITA pIV activation, and selected STAT1 regulated genes were variably downregulated by E₂ in transfected and endogenous ERα positive breast cancer cells, whereas STAT1 signaling was noticeably augmented in ERα⁻ breast cancer cells. Collectively, these results imply immune escape mechanisms in ERα⁺ breast cancer may be facilitated through an ERα suppressive mechanism on IFN-γ signaling.

  4. Two-Stage Translational Control of Dentate Gyrus LTP Consolidation Is Mediated by Sustained BDNF-TrkB Signaling to MNK

    Directory of Open Access Journals (Sweden)

    Debabrata Panja

    2014-11-01

    Full Text Available BDNF signaling contributes to protein-synthesis-dependent synaptic plasticity, but the dynamics of TrkB signaling and mechanisms of translation have not been defined. Here, we show that long-term potentiation (LTP consolidation in the dentate gyrus of live rodents requires sustained (hours BDNF-TrkB signaling. Surprisingly, this sustained activation maintains an otherwise labile signaling pathway from TrkB to MAP-kinase-interacting kinase (MNK. MNK activity promotes eIF4F translation initiation complex formation and protein synthesis in mechanistically distinct early and late stages. In early-stage translation, MNK triggers release of the CYFIP1/FMRP repressor complex from the 5′-mRNA cap. In late-stage translation, MNK regulates the canonical translational repressor 4E-BP2 in a synapse-compartment-specific manner. This late stage is coupled to MNK-dependent enhanced dendritic mRNA translation. We conclude that LTP consolidation in the dentate gyrus is mediated by sustained BDNF signaling to MNK and MNK-dependent regulation of translation in two functionally and mechanistically distinct stages.

  5. Reproducible and sustained regulation of Gαs signalling using a metazoan opsin as an optogenetic tool.

    Directory of Open Access Journals (Sweden)

    Helena J Bailes

    Full Text Available Originally developed to regulate neuronal excitability, optogenetics is increasingly also used to control other cellular processes with unprecedented spatiotemporal resolution. Optogenetic modulation of all major G-protein signalling pathways (Gq, Gi and Gs has been achieved using variants of mammalian rod opsin. We show here that the light response driven by such rod opsin-based tools dissipates under repeated exposure, consistent with the known bleaching characteristics of this photopigment. We continue to show that replacing rod opsin with a bleach resistant opsin from Carybdea rastonii, the box jellyfish, (JellyOp overcomes this limitation. Visible light induced high amplitude, reversible, and reproducible increases in cAMP in mammalian cells expressing JellyOp. While single flashes produced a brief cAMP spike, repeated stimulation could sustain elevated levels for 10s of minutes. JellyOp was more photosensitive than currently available optogenetic tools, responding to white light at irradiances ≥1 µW/cm(2. We conclude that JellyOp is a promising new tool for mimicking the activity of Gs-coupled G protein coupled receptors with fine spatiotemporal resolution.

  6. Direct impact of the sustained decline in the photosystem II efficiency upon plant productivity at different developmental stages.

    Science.gov (United States)

    Tian, Yonglan; Ungerer, Petra; Zhang, Huayong; Ruban, Alexander V

    2017-05-01

    The impact of chronic photoinhibition of photosystem II (PSII) on the productivity of plants remains unknown. The present study investigated the influences of persistent decline in the PSII yield on morphology and productivity of Arabidopsis plants that were exposed to lincomycin at two different developmental stages (seedling and rosette stage). The results indicated that, although retarded, the lincomycin treated plants were able to accomplish the entire growth period with only 50% of the maximum quantum yield of primary photochemistry (Fv/Fm) of the control plants. The decline in quantum yield limited the electron transport rate (ETR). The impact of lincomycin on NPQ was not significant in seedlings, but was pronounced in mature plants. The treated plants produced an above ground biomass of 50% compared to control plants. Moreover, a linear relationship was found between the above ground biomass and total rosette leaf area, and the slope was decreased due to photoinhibition. The starch accumulation was highly inhibited by lincomycin treatment. Lincomycin induced a significant decrease in seed yield with plants treated from the rosette state showing higher yield than those treated from the seedling stage. Our data suggest that the sustained decline of PSII efficiency decreases plant productivity by constraining the ETR, leaf development and starch production. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. The S(1) split signal of photosystem II; a tyrosine-manganese coupled interaction.

    Science.gov (United States)

    Cox, Nicholas; Ho, Felix M; Pewnim, Naray; Steffen, Ronald; Smith, Paul J; Havelius, Kajsa G V; Hughes, Joseph L; Debono, Lesley; Styring, Stenbjörn; Krausz, Elmars; Pace, Ron J

    2009-07-01

    Detailed optical and EPR analyses of states induced in dark-adapted PS II membranes by cryogenic illumination permit characterization and quantification of all pigment derived donors and acceptors, as well as optically silent (in the visible, near infrared) species which are EPR active. Near complete turnover formation of Q(A)((-)) is seen in all centers, but with variable efficiency, depending on the donor species. In minimally detergent-exposed PS II membranes, negligible (ii) reduced cytochrome b(559) ( approximately 30-50% centers), and (iii) an organic donor, possibly an amino acid side chain, ( approximately 30% centers).

  8. Punch stretching process monitoring using acoustic emission signal analysis. II - Application of frequency domain deconvolution

    Science.gov (United States)

    Liang, Steven Y.; Dornfeld, David A.; Nickerson, Jackson A.

    1987-01-01

    The coloring effect on the acoustic emission signal due to the frequency response of the data acquisition/processing instrumentation may bias the interpretation of AE signal characteristics. In this paper, a frequency domain deconvolution technique, which involves the identification of the instrumentation transfer functions and multiplication of the AE signal spectrum by the inverse of these system functions, has been carried out. In this way, the change in AE signal characteristics can be better interpreted as the result of the change in only the states of the process. Punch stretching process was used as an example to demonstrate the application of the technique. Results showed that, through the deconvolution, the frequency characteristics of AE signals generated during the stretching became more distinctive and can be more effectively used as tools for process monitoring.

  9. Angiotensin II Induces C-Reactive Protein Expression via AT1-ROS-MAPK-NF-κB Signal Pathway in Hepatocytes

    Directory of Open Access Journals (Sweden)

    Jingjing Zhao

    2013-09-01

    Full Text Available Background: C-reactive protein (CRP participates in development of inflammatory diseases. Hepatocytes are a major contributor of circulating CRP. Although angiotensin II (Ang II is known to evoke inflammatory response, it remains unknown whether Ang II induces CRP expression in hepatocytes. The present study observed effect of Ang II on CRP expression and the related signal pathway in hepatocytes. Methods: mRNA and protein expressions in human hepatocytes were determined with RT-PCR and Western blot respectively. Reactive oxygen species (ROS was measured using a fluorescence probe. CRP in liver and serum of rats was determined by immunohistochemistry and ELISA respectively. Results: Ang II induced mRNA and protein expression of CRP in hepatocytes and increased CRP production in liver and CRP level in serum. Losartan reduced Ang II- induced CRP expression in hepatocytes. Losartan and thenoyltrifluoroacetone decreased Ang II-stimulated ROS production. N-acetylcysteine antagonized Ang II-induced CRP expression. Losartan and N-acetylcysteine inhibited Ang II-activated ERK1/2. Unlike ERK1/2, only losartan inhibited Ang II-activated JNK. Furthermore, pyrrolidine dithiocarbamate abolished Ang II-induced CRP expression. Conclusion: Ang II has ability to induce CRP expression in hepatocytes in vitro and in vivo through AT1 receptor followed by ROS, MAPK and NF-κB signal pathway.

  10. Engineering fibrin-binding TGF-β1 for sustained signaling and contractile function of MSC based vascular constructs

    Science.gov (United States)

    Liang, Mao-Shih; Andreadis, Stelios T.

    2011-01-01

    We present a strategy to conjugate TGF-β1 into fibrin hydrogels to mimic the in vivo presentation of the growth factor in a 3D context. To this end, we engineered fusion proteins between TGF-β1 and a bi-functional peptide composed of a Factor XIII domain and a plasmin cleavage site. In another version the protease cleavage site was omitted to examine whether the growth factor that could not be released from the scaffold by cells had different effects on tissue constructs. The optimal insertion site which yielded correctly processed, functional protein was found between the latency associated peptide and mature TGF-β1 domains. In solution the fusion proteins exhibited similar biological activity as native TGF-β1 as evidenced by inhibition of cell proliferation and promoter activity assays. Immunoprecipitation experiments demonstrated that the fusion TGF-β1 protein bound to fibrinogen in a Factor XIII dependent manner and could be released from the peptide by the action of plasmin. In contrast to bolus delivery, immobilized TGF-β1 induced sustained signaling in fibrin-embedded cells for several days as evidenced by Smad2 phosphorylation. Prolonged pathway activation correlated with enhanced contractile function of vascular constructs prepared from hair follicle mesenchymal stem cells or bone marrow derived smooth muscle cells. Our results suggest that fibrin-immobilized TGF-β1 may be used to enhance the local microenvironment and improve the function of engineered tissues in vitro and potentially also after implantation in vivo where growth factor delivery faces overwhelming challenges. PMID:21864893

  11. Sphingosine-1-phosphate signalling-a key player in the pathogenesis of Angiotensin II-induced hypertension.

    Science.gov (United States)

    Meissner, Anja; Miro, Francesc; Jiménez-Altayó, Francesc; Jurado, Andrés; Vila, Elisabet; Planas, Anna M

    2017-02-01

    Hypertension is a complex condition involving functional and structural alterations of the microvasculature and an activation of the immune system. T-lymphocytes play a crucial role during the development of hypertension in experimental models, yet the underlying mechanisms remain elusive. Lymphocyte egress from lymph nodes is controlled by sphingosine-1-phosphate (S1P), a natural lipid mediator regulating immune cell and vascular function in health and disease. We therefore investigated the involvement of S1P signalling in the pathogenesis of hypertension. Angiotensin-II (AngII) treatment resulted in high blood pressure (BP) associated to increased plasma S1P and circulating T-cell counts. T-cell egress from lymph nodes was found to be a critical initial step for the onset of hypertension as fingolimod, a S1P-receptor agonist sequestering lymphocytes in the lymph nodes and inducing lymphopenia, blunted BP responses to AngII. Furthermore, activity of S1P-generating enzyme type 2 (SphK2) in haematopoietic cells critically contributed to AngII-induced lymphocyte mobilization from the lymph nodes as SphK2-/- mice and mice where SphK2 was ablated only in the haematopoietic system presented an accumulation of T-cells in mesenteric lymph nodes and a blunted BP response. In addition, deregulation of vascular SphK2 expression associated to a thrombo-inflammatory phenotype of the microvasculature, and to functional alterations of small resistance arteries. The presented results point to a critical involvement of S1P and its signalling axis in the pathogenesis of hypertension. Specifically, SphK2 evolves as key player in immune cell trafficking and vascular dysfunction contributing to the development of overt hypertension. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions, please email: journals.permissions@oup.com.

  12. The orally active glutamate carboxypeptidase II inhibitor E2072 exhibits sustained nerve exposure and attenuates peripheral neuropathy.

    Science.gov (United States)

    Wozniak, Krystyna M; Wu, Ying; Vornov, James J; Lapidus, Rena; Rais, Rana; Rojas, Camilo; Tsukamoto, Takashi; Slusher, Barbara S

    2012-12-01

    Peripheral neuropathy from nerve trauma is a significant problem in the human population and often constitutes a dose-limiting toxicity in patients receiving chemotherapy. (3-2-Mercaptoethyl)biphenyl-2,3-dicarboxylic acid (E2072) is a potent (K(i) = 10 nM), selective, and orally available inhibitor of glutamate carboxypeptidase II (GCPII). Here, we report that E2072 attenuates hyperalgesia and nerve conduction velocity deficits in preclinical rodent models of neuropathic pain and oxaliplatin-induced neuropathy. In the chronic constrictive injury model, orally administered E2072 reversed pre-existing thermal hyperalgesia in rats in a dose-dependent fashion with a minimally effective dose of 0.1 mg/kg/day. It is noteworthy that multiple days of dosing of E2072 were required before analgesia was realized even though GCPII inhibitory exposures were achieved on the first day of dosing. In addition, analgesia was found to persist for up to 7 days after cessation of dosing, consistent with E2072's pharmacokinetic profile and sustained exposure. Furthermore, in a chronic oxaliplatin-induced neuropathy model (6 mg/kg i.p. oxaliplatin twice weekly for 4 weeks), female BALB/c mice receiving daily oral E2072 at 1.0 and 0.1 mg/kg displayed no deficits in either caudal or digital velocity compared with significant deficits observed in mice treated with oxaliplatin alone (12 ± 3 and 9 ± 2%, respectively). Similar findings were seen with oxaliplatin-induced digital and caudal amplitude deficits. It is noteworthy that E2072 showed no interference with the antineoplastic efficacy of oxaliplatin in mice bearing leukemia (L1210), even at doses 100 times its neuroprotective/analgesic dose, indicating a selective effect on neuropathy. These data support the therapeutic utility of GCPII inhibitors in neuropathy and neuropathic pain.

  13. Angiotensin II AT1 receptors mediate neuronal sensitization and sustained blood pressure response induced by a single injection of amphetamine.

    Science.gov (United States)

    Marchese, N A; Paz, M C; Caeiro, X; Dadam, F M; Baiardi, G; Perez, M F; Bregonzio, C

    2017-01-06

    A single exposure to amphetamine induces neurochemical sensitization in striatal areas. The neuropeptide angiotensin II, through AT1 receptors (AT1-R) activation, is involved in these responses. However, amphetamine-induced alterations can be extended to extra-striatal areas involved in blood pressure control and their physiological outcomes. Our aim for the present study was to analyze the possible role for AT1-R in these events using a two-injection protocol and to further characterize the proposed AT1-R antagonism protocol. Central effect of orally administered AT1-R blocker (Candesartan, 3mg/kg p.o.×5days) in male Wistar rats was analyzed by spontaneous activity of neurons within locus coeruleus. In another group of animals pretreated with the AT1-R blocker or vehicle, sensitization was achieved by a single administration of amphetamine (5mg/kg i.p. - day 6) followed by a 3-week period off drug. On day 27, after receiving an amphetamine challenge (0.5mg/kg i.p.), we evaluated: (1) the sensitized c-Fos expression in locus coeruleus (LC), nucleus of the solitary tract (NTS), caudal ventrolateral medulla (A1) and central amygdala (CeAmy); and (2) the blood pressure response. AT1-R blockade decreased LC neurons' spontaneous firing rate. Moreover, sensitized c-Fos immunoreactivity in TH+neurons was found in LC and NTS; and both responses were blunted by the AT1-R blocker pretreatment. Meanwhile, no differences were found neither in CeAmy nor A1. Sensitized blood pressure response was observed as sustained changes in mean arterial pressure and was effectively prevented by AT1-R blockade. Our results extend AT1-R role in amphetamine-induced sensitization over noradrenergic nuclei and their cardiovascular output. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. HI Fluctuations at Large Redshifts: II – the Signal Expected for the ...

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    redshift sand using these observations to probe large scale structures. Our approach has been based on the ... The antennas all point in the same direction along the unit vector n which we take to be vertically upwards. ... that were used, the predictions for 610 MHz in paper II are also incorrect. The HI emission originates ...

  15. Effect of Schiff base Cu(II) complexes on signaling pathways in HT-29 cells.

    Science.gov (United States)

    Koňariková, Katarína; Perdikaris, Georgios A; Gbelcova, Helena; Andrezálová, Lucia; Švéda, Martin; Ruml, Tomáš; Laubertová, Lucia; Žitňanová, Ingrid

    2016-11-01

    Schiff base copper (II) complexes are known for their anticancer, antifungal, antiviral and anti‑inflammatory activities. The aim of the current study was to investigate biological effects of Schiff base Cu (II) complexes (0.001‑100 µmol/l)‑[Cu2(sal‑D, L‑glu)2(isoquinoline)2]·2C2H5OH (1), [Cu(sal‑5‑met‑L‑glu)(H2O)].H2O (2), [Cu(ethanol)2(imidazole)4][Cu2(sal‑D, L-glu)2(imidazole)2] (3), [Cu(sal‑D,L‑glu)(2‑methylimidazole)] (4) on the human colon carcinoma cells HT‑29, the mouse noncancerous cell line NIH‑3T3 and the human noncancerous fibroblast cell line VH10. The results suggested that Cu (II) complexes exhibit cytotoxic effects against the HT‑29 cell line, while complexes 3 and 4 were the most effective. Subsequent to 72 h of incubation, apoptosis was observed in the HT‑29 cells induced by Cu (II) complexes 1 (0.1, 1, 10 and 50 µmol/l), 2 (1, 10, 50 and 100 µmol/l), 3 (0.01, 1, 10 and 50 µmol/l) and 4 (0.01, 0.1, 1 and 10 µmol/l). The apoptotic pathways activated by the Cu (II) complexes were identified. The results indicated that complexes 2, 3 and 4 were able to induce the mitochondria‑dependent pathway of apoptosis in HT‑29 cells, while complex 1 was obsered to activate the extrinsic pathway of apoptosis. The levels of the anti‑apoptotic protein Bcl‑2 were reduced and those of the pro‑apoptotic protein Bax increased following treatment with complexes 2, 3 and 4. Complex 1 had no effect on Bax protein expression. Complexes 2 and 3 induced elevation of cytochrome c (cyt c), while complex 4 induced a time‑dependent elevation of cyt c levels. No cyt c was detected in HT‑29 cells exposed to complex 1, suggesting that Cu (II) complexes activated the extrinsic pathway of apoptosis. The results from the current study in addition to previous studies suggest that Schiff base Cu (II) complexes have potential as novel anticancer drugs.

  16. Correlated behavior of the EPR signal of cytochrome b-559 heme Fe(III) ligated by OH- and the multiline signal of the Mn cluster in PS-II membrane fragments.

    Science.gov (United States)

    Fiege, R; Shuvalov, V A

    1996-05-27

    EPR signals of Cyt b-559 heme Fe(III) ligated by OH- and the multiline signal of the Mn cluster in PS-II membrane fragments have been investigated. In 2,3-dicyano-5,6-dichloro-p-benzoquinone-oxidized PS-II membrane fragments the light-induced decrease of the EPR signal of the heme Fe(III)-OH- is accompanied by the appearance of the EPR multiline signal of the Mn cluster. Addition of F- ions, which act as a stronger ligand for heme Fe(III) than OH-, decreases to the same extent the dark- and light-induced signal of the heme Fe(III)-OH- and the light-induced multiline signal of the Mn cluster. These results are discussed in terms of the light-induced formation of a bound OH' radical shared between the Cyt b-559 heme Fe and the Mn cluster as a first step of water oxidation.

  17. Limiting characteristics of a superconducting quantum interferometer. II. Signal-to-noise ratio

    Energy Technology Data Exchange (ETDEWEB)

    Butikov, E.I.; Feofilov, S.P.

    1980-11-01

    In the approximation of small fluctuations, the spectral density of intrinsic thermal noise limiting the maximal sensitivity of a constant-current SQUID is found in the low-frequency region. The dependence of the signal-to-noise ratio on the SQUID parameters and operating conditions of an interferometer with low-frequency magnetic flux modulation is studied. Estimates are given for the smallest detectable magnetic flux corresponding to optimal operating conditions of a SQUID.

  18. Remote impact analysis by use of propagated acceleration signals, II: Comparison between theory and experiment

    Science.gov (United States)

    Jordan, R. W.; Whiston, G. S.

    1984-11-01

    The techniques for remote impact analysis developed in Part I [1] are analyzed from an experimental point of view. Comparison is made between the theoretical and experimental Timoshenko transfer functions between the remote acceleration transform and the impact force-time history transform. The inversion process has been applied with success to experimental impacting data; good representations of impact force-time histories have been obtained even in the presence of signal contamination.

  19. SphK1 inhibitor SKI II inhibits the proliferation of human hepatoma HepG2 cells via the Wnt5A/β-catenin signaling pathway.

    Science.gov (United States)

    Liu, Hong; Zhang, Cai-Xia; Ma, Yan; He, Hong-Wei; Wang, Jia-Ping; Shao, Rong-Guang

    2016-04-15

    Sphingosine 1-phosphate (S1P) promotes cell growth, proliferation and survival. Sphingosine kinase 1 (SphK1), which converts sphingosine to S1P, is a key promoter in cancer. We previously found that the SphK1 inhibitor II (SKI II), suppresses the cell growth and induces apoptosis in human hepatoma HepG2 cells. However, the precise regulatory mechanism and signaling pathway on SKI II inhibiting tumor growth remains unknown. The expressions of β-catenin and related molecules of Wnt/β-catenin signal were detected by western blot in HepG2 cells. And the mRNA expression of β-catenin was detected by RT-PCR. The Wnt5A gene was silenced by siRNA. The colony formation was determined by staining with crystal violet. And the cell growth was examined by SRB assay and BrdU assay. We found that SKI II decreased the expression of β-catenin and the downstream molecules of β-catenin signal pathway and promotes the β-catenin degradation. In addition, SKI II induced the expression of Wnt5A, and then triggered β-catenin degradation. Furthermore, silencing Wnt5A decreased the anti-tumor effects of SKI II through recovering the expressions of β-catenin and downstream molecules of β-catenin signal pathway. SKI II-induced downregulation of HepG2 cell proliferation was associated with Wnt signaling pathway through Wnt5A-mediated β-catenin degradation. Our study revealed that a novel signal pathway was involved in SKI II-inhibited cell proliferation in human hepatoma cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Notch signaling sustains the expression of Mcl-1 and the activity of eIF4E to promote cell survival in CLL.

    Science.gov (United States)

    De Falco, Filomena; Sabatini, Rita; Del Papa, Beatrice; Falzetti, Franca; Di Ianni, Mauro; Sportoletti, Paolo; Baldoni, Stefano; Screpanti, Isabella; Marconi, Pierfrancesco; Rosati, Emanuela

    2015-06-30

    In chronic lymphocytic leukemia (CLL), Notch1 and Notch2 signaling is constitutively activated and contributes to apoptosis resistance. We show that genetic inhibition of either Notch1 or Notch2, through small-interfering RNA, increases apoptosis of CLL cells and is associated with decreased levels of the anti-apoptotic protein Mcl-1. Thus, Notch signaling promotes CLL cell survival at least in part by sustaining Mcl-1 expression. In CLL cells, an enhanced Notch activation also contributes to the increase in Mcl-1 expression and cell survival induced by IL-4.Mcl-1 downregulation by Notch targeting is not due to reduced transcription or degradation by caspases, but in part, to increased degradation by the proteasome. Mcl-1 downregulation by Notch targeting is also accompanied by reduced phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), suggesting that this protein is another target of Notch signaling in CLL cells.Overall, we show that Notch signaling sustains CLL cell survival by promoting Mcl-1 expression and eIF4E activity, and given the oncogenic role of these factors, we underscore the therapeutic potential of Notch inhibition in CLL.

  1. XIAP acts as a switch between type I and type II FAS-induced apoptosis signalling

    OpenAIRE

    Jost, Philipp J.; Grabow, Stephanie; Gray, Daniel; McKenzie, Mark D.; Nachbur, Ueli; Huang, David C.S; Bouillet, Philippe; Thomas, Helen E.; Borner, Christoph; Silke, John; Strasser, Andreas; Kaufmann, Thomas

    2009-01-01

    FAS (APO-1/CD95) and its physiological ligand, FASL, regulate apoptotic death of unwanted or dangerous cells in many tissues, functioning as a guardian against autoimmunity and cancer development1-4. Distinct cell types differ in the mechanisms by which the ‘death receptor’ FAS triggers their apoptosis1-4. In type I cells, such as lymphocytes, activation of ‘effector caspases’ by FAS-induced activation of caspase-8 suffices for cell killing whereas in type II cells, including hepatocytes and ...

  2. Angiotensin II type 1a receptors in subfornical organ contribute towards chronic intermittent hypoxia-associated sustained increase in mean arterial pressure.

    Science.gov (United States)

    Saxena, Ashwini; Little, Joel T; Nedungadi, T Prashant; Cunningham, J Thomas

    2015-03-01

    Sleep apnea is associated with hypertension. The mechanisms contributing to a sustained increase in mean arterial pressure (MAP) even during normoxic awake-state remain unknown. Rats exposed to chronic intermittent hypoxia for 7 days, a model of the hypoxemia associated with sleep apnea, exhibit sustained increases in MAP even during the normoxic dark phase. Activation of the renin-angiotensin system (RAS) has been implicated in chronic intermittent hypoxia (CIH) hypertension. Since the subfornical organ (SFO) serves as a primary target for the central actions of circulating ANG II, we tested the effects of ANG II type 1a receptor (AT1aR) knockdown in the SFO on the sustained increase in MAP in this CIH model. Adeno-associated virus carrying green fluorescent protein (GFP) and small-hairpin RNA against either AT1aR or a scrambled control sequence (SCM) was stereotaxically injected in the SFO of rats. After recovery, MAP, heart rate, respiratory rate, and activity were continuously recorded using radiotelemetry. In the normoxic groups, the recorded variables did not deviate from the baseline values. Both CIH groups exhibited significant increases in MAP during CIH exposures (P dark phase in the CIH groups, only the SCM-injected group exhibited a sustained increase in MAP (P < 0.05). The AT1aR-CIH group showed significant decreases in FosB/ΔFosB staining in the median preoptic nucleus and the paraventricular nuclei of the hypothalamus compared with the SCM-CIH group. Our data indicate that AT1aRs in the SFO are critical for the sustained elevation in MAP and increased FosB/ΔFosB expression in forebrain autonomic nuclei associated with CIH. Copyright © 2015 the American Physiological Society.

  3. The disintegrin and metalloproteinase ADAM12 contributes to TGF-β signaling through interaction with the type II receptor

    Science.gov (United States)

    Atfi, Azeddine; Dumont, Emmanuelle; Colland, Frédéric; Bonnier, Dominique; L'Helgoualc'h, Annie; Prunier, Céline; Ferrand, Nathalie; Clément, Bruno; Wewer, Ulla M.; Théret, Nathalie

    2007-01-01

    Transforming growth factor-β (TGF-β) regulates a wide variety of biological processes through two types of Ser/Thr transmembrane receptors: the TGF-β type I receptor and the TGF-β type II receptor (TβRII). Upon ligand binding, TGF-β type I receptor activated by TβRII propagates signals to Smad proteins, which mediate the activation of TGF-β target genes. In this study, we identify ADAM12 (a disintegrin and metalloproteinase 12) as a component of the TGF-β signaling pathway that acts through association with TβRII. We found that ADAM12 functions by a mechanism independent of its protease activity to facilitate the activation of TGF-β signaling, including the phosphorylation of Smad2, association of Smad2 with Smad4, and transcriptional activation. Furthermore, ADAM12 induces the accumulation of TβRII in early endosomal vesicles and stabilizes the TβRII protein presumably by suppressing the association of TβRII with Smad7. These results define ADAM12 as a new partner of TβRII that facilitates its trafficking to early endosomes in which activation of the Smad pathway is initiated. PMID:17620406

  4. Pivotal role of cardiomyocyte TGF-β signaling in the murine pathological response to sustained pressure overload

    NARCIS (Netherlands)

    Koitabashi, Norimichi; Danner, Thomas; Zaiman, Ari L.; Pinto, Yigal M.; Rowell, Janelle; Mankowski, Joseph; Zhang, Dou; Nakamura, Taishi; Takimoto, Eiki; Kass, David A.

    2011-01-01

    The cardiac pathological response to sustained pressure overload involves myocyte hypertrophy and dysfunction along with interstitial changes such as fibrosis and reduced capillary density. These changes are orchestrated by mechanical forces and factors secreted between cells. One such secreted

  5. Expression of the MHC class II in triple-negative breast cancer is associated with tumor-infiltrating lymphocytes and interferon signaling.

    Directory of Open Access Journals (Sweden)

    In Ah Park

    Full Text Available Tumor-infiltrating lymphocytes (TILs have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC. Several mechanisms for TIL influx in TNBC have been elucidated. Major histocompatibility complex class II (MHC-II is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer. We aimed to examine the relationship between MHC-II expression in tumor cells and the amount of TILs in 681 patients with TNBC. Further, the prognostic significance of MHC-II and the association of MHC-II with a couple of molecules involved in the interferon signaling pathway were investigated using immunohistochemical staining. Higher MHC-II expression in tumor cells was associated with the absence of lymphovascular invasion (p = 0.042; larger amounts of TILs (p < 0.001; frequent formations of tertiary lymphoid structures (p < 0.001; higher expression of myxovirus resistance gene A, one of the main mediators of the interferon signaling pathway (p < 0.001; and higher expression of double-stranded RNA-activated protein kinase, which can be induced by interferons (p = 0.008. Moreover, tumors that showed high MHC class I expression and any positivity for MHC-II had larger amounts of CD4- and CD8-positive T lymphocytes (p < 0.001. Positive MHC-II expression in tumor cells was associated with better disease-free survival in patients who had lymph node metastasis (p = 0.009. In conclusion, MHC-II expression in tumor cells was closely associated with an increase in TIL number and interferon signaling in TNBC. Further studies are warranted to improve our understanding regarding TIL influx, as well as patients' responses to immunotherapy.

  6. Angiotensin II type 2 receptor signaling significantly attenuates growth of murine pancreatic carcinoma grafts in syngeneic mice

    Directory of Open Access Journals (Sweden)

    Troyer Deryl

    2010-02-01

    Full Text Available Abstract Background Pancreatic cancer is one of the most aggressive human malignancies, with a very poor prognosis. To evaluate the effect of angiotensin II (Ang II type 2 receptor (AT2 expression in the host's body on the growth of pancreatic carcinoma, we have investigated the growth of mouse pancreatic ductal carcinoma grafts in syngeneic wild type and AT2 receptor-deficient (AT2-KO mice. Methods The role of AT2 receptor-signaling in stromal cells on the growth of murine pancreatic carcinoma cells (PAN02 was studied using various in vitro and in vivo assays. In vivo cell proliferation, apoptosis, and vasculature in tumors were monitored by Ki-67 immunostaining, TUNEL assay, and von Willebrand factor immunostaining, respectively. In the co-culture study, cell proliferation was measured by MTT cell viability assay. All the data were analyzed using t-test and data were treated as significant when p Results Our results show that the growth of subcutaneously transplanted syngeneic xenografts of PAN02 cells, mouse pancreatic ductal carcinoma cells derived from the C57/BL6 strain, was significantly faster in AT2-KO mice compared to control wild type mice. Immunohistochemical analysis of tumor tissue revealed significantly more Ki-67 positive cells in xenografts grown in AT2-KO mice than in wild type mice. The index of apoptosis is slightly higher in wild type mice than in AT2-KO mice as evaluated by TUNEL assay. Tumor vasculature number was significantly higher in AT2-KO mice than in wild type mice. In vitro co-culture studies revealed that the growth of PAN02 cells was significantly decreased when grown with AT2 receptor gene transfected wild type and AT2-KO mouse-derived fibroblasts. Faster tumor growth in AT2-KO mice may be associated with higher VEGF production in stromal cells. Conclusions These results suggest that Ang II regulates the growth of pancreatic carcinoma cells through modulating functions of host stromal cells; Moreover, Ang II AT2

  7. Biased signaling of the angiotensin II type 1 receptor can be mediated through distinct mechanisms

    DEFF Research Database (Denmark)

    Bonde, Marie Mi; Hansen, Jonas Tind; Sanni, Samra Joke

    2010-01-01

    receptor. Several studies on pathway separation have been performed, many of these on the Angiotensin II type 1 receptor (AT1R). It has been shown that certain ligands or mutations facilitate internalization and/or recruitment of β-arrestins without activation of G proteins. However, the underlying...... molecular mechanisms remain largely unresolved. For instance, it is unclear whether such selective G protein-uncoupling is caused by a lack of ability to interact with G proteins or rather by an increased ability of the receptor to recruit β-arrestins. Since uncoupling of G proteins by increased ability...... to recruit β-arrestins could lead to different cellular or in vivo outcomes than lack of ability to interact with G proteins, it is essential to distinguish between these two mechanisms....

  8. Nonclassical Mechanisms of Progesterone Action in the Brain: II. Role of Calmodulin-Dependent Protein Kinase II in Progesterone-Mediated Signaling in the Hypothalamus of Female Rats

    Science.gov (United States)

    Balasubramanian, Bhuvana; Portillo, Wendy; Reyna, Andrea; Chen, Jian Zhong; Moore, Anthony N.; Dash, Pramod K.; Mani, Shaila K.

    2008-01-01

    In addition to the activation of classical progestin receptor-dependent genomic pathway, progesterone (P) can activate nonclassical, membrane-initiated signaling pathways in the brain. We recently demonstrated rapid P activation of second-messenger kinases, protein kinase A, and protein kinase C in the ventromedial nucleus (VMN) and preoptic area (POA) of rat brain. To determine whether P can activate yet another Ca+2dependent kinase, we examined the rapid P modulation of calcium and calmodulin-dependent protein kinase II (CaMKII) in the VMN and POA in female rats. A rapid P-initiated activation of CaMKII basal activity was observed in the VMN but not the POA at 30 min. Estradiol benzoate (EB) priming enhanced this CaMKII basal activity in both the VMN and POA. CaMKII protein levels and phosphorylation of Thr-286 moiety on CaMKII, however, remained unchanged with EB and/or P treatments, suggesting that the changes in the CaMKII kinase activity are due to rapid P modulation of the kinase activity and not its synthesis or autoactivation. Furthermore, intracerebroventricular (icv) administration of a CaMKII-specific inhibitor, KN-93, 30 min prior to the P infusion, in EB-primed, ovariectomized female rats inhibited CaMKII activation but not protein kinase A and protein kinase C activities. Interestingly, icv administration of KN-93 30 min prior to P infusion (icv) resulted in a reduction but not total inhibition of P-facilitated lordosis response in EB-primed female rats. These observations suggest a redundancy or, alternately, a hierarchy in the P-regulated activation of kinase signaling cascades in female reproductive behavior. PMID:18617607

  9. Biomedical signals and sensors II linking acoustic and optic biosignals and biomedical sensors

    CERN Document Server

    Kaniusas, Eugenijus

    2015-01-01

    The book set develops a bridge between physiologic mechanisms and diagnostic human engineering. While the first volume is focused on the interface between physiologic mechanisms and the resultant biosignals, this second volume is devoted to the interface between biosignals and biomedical sensors. That is, in the first volume, the physiologic mechanisms determining biosignals are described from the basic cellular level up to their advanced mutual coordination level. This second volume, considers the genesis of acoustic and optic biosignals and the associated sensing technology from a strategic point of view. As a novelty, this book discusses heterogeneous biosignals within a common frame. This frame comprises both the biosignal formation path from the biosignal source at the physiological level to biosignal propagation in the body, and the biosignal sensing path from the biosignal transmission in the sensor applied on the body up to its conversion to a, usually electric, signal. Some biosignals arise in the co...

  10. The Recording and Quantification of Event-Related Potentials: II. Signal Processing and Analysis

    Directory of Open Access Journals (Sweden)

    Paniz Tavakoli

    2015-06-01

    Full Text Available Event-related potentials are an informative method for measuring the extent of information processing in the brain. The voltage deflections in an ERP waveform reflect the processing of sensory information as well as higher-level processing that involves selective attention, memory, semantic comprehension, and other types of cognitive activity. ERPs provide a non-invasive method of studying, with exceptional temporal resolution, cognitive processes in the human brain. ERPs are extracted from scalp-recorded electroencephalography by a series of signal processing steps. The present tutorial will highlight several of the analysis techniques required to obtain event-related potentials. Some methodological issues that may be encountered will also be discussed.

  11. Information theory in systems biology. Part II: protein-protein interaction and signaling networks.

    Science.gov (United States)

    Mousavian, Zaynab; Díaz, José; Masoudi-Nejad, Ali

    2016-03-01

    By the development of information theory in 1948 by Claude Shannon to address the problems in the field of data storage and data communication over (noisy) communication channel, it has been successfully applied in many other research areas such as bioinformatics and systems biology. In this manuscript, we attempt to review some of the existing literatures in systems biology, which are using the information theory measures in their calculations. As we have reviewed most of the existing information-theoretic methods in gene regulatory and metabolic networks in the first part of the review, so in the second part of our study, the application of information theory in other types of biological networks including protein-protein interaction and signaling networks will be surveyed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. MAP kinase-signaling controls nuclear translocation of tripeptidyl-peptidase II in response to DNA damage and oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Preta, Giulio; Klark, Rainier de; Chakraborti, Shankhamala [Center for Molecular Medicine (CMM), Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm (Sweden); Glas, Rickard, E-mail: rickard.glas@ki.se [Center for Molecular Medicine (CMM), Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm (Sweden)

    2010-08-27

    Research highlights: {yields} Nuclear translocation of TPPII occurs in response to different DNA damage inducers. {yields} Nuclear accumulation of TPPII is linked to ROS and anti-oxidant enzyme levels. {yields} MAPKs control nuclear accumulation of TPPII. {yields} Inhibited nuclear accumulation of TPPII decreases DNA damage-induced {gamma}-H2AX expression. -- Abstract: Reactive oxygen species (ROS) are a continuous hazard in eukaroytic cells by their ability to cause damage to biomolecules, in particular to DNA. Previous data indicated that the cytosolic serine peptidase tripeptidyl-peptidase II (TPPII) translocates into the nucleus of most tumor cell lines in response to {gamma}-irradiation and ROS production; an event that promoted p53 expression as well as caspase-activation. We here observed that nuclear translocation of TPPII was dependent on signaling by MAP kinases, including p38MAPK. Further, this was caused by several types of DNA-damaging drugs, a DNA cross-linker (cisplatinum), an inhibitor of topoisomerase II (etoposide), and to some extent also by nucleoside-analogues (5-fluorouracil, hydroxyurea). In the minority of tumor cell lines where TPPII was not translocated into the nucleus in response to DNA damage we observed reduced intracellular ROS levels, and the expression levels of redox defense systems were increased. Further, treatment with the ROS-inducer {gamma}-hexa-chloro-cyclohexane ({gamma}-HCH, lindane), an inhibitor of GAP junctions, restored nuclear translocation of TPPII in these cell lines upon {gamma}-irradiation. Moreover, blocking nuclear translocation of TPPII in etoposide-treated cells, by using a peptide-derived inhibitor (Z-Gly-Leu-Ala-OH), attenuated expression of {gamma}-H2AX in {gamma}-irradiated melanoma cells. Our results indicated a role for TPPII in MAPK-dependent DNA damage signaling.

  13. Urotensin II induction of neonatal cardiomyocyte hypertrophy involves the CaMKII/PLN/SERCA 2a signaling pathway.

    Science.gov (United States)

    Shi, Hongtao; Han, Qinghua; Xu, Jianrong; Liu, Wenyuan; Chu, Tingting; Zhao, Li

    2016-05-25

    Although studies have shown that Urotensin II (UII) can induce cardiomyocyte hypertrophy and UII-induced cardiomyocyte hypertrophy model has been widely used for hypertrophy research, but its precise mechanism remains unknown. Recent researches have demonstrated that UII-induced cardiomyocyte hypertrophy has a relationship with the changes of intracellular Ca(2+) concentration. Therefore, the aim of this study was to investigate the mechanisms of cardiomyocyte hypertrophy induced by UII and to explore whether the calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated up-regulating of phospholamban (PLN) Thr17-phosphorylation signaling pathway contributed to UII-induced cardiomyocyte hypertrophy. Primary cultures of neonatal rat cardiomyocytes were stimulated for 48h with UII. Cell size, protein/DNA contents and intracellular Ca(2+) were determined. Phosphorylated and total forms of CaMKII, PLN and the total amount of serco/endo-plasmic reticulum ATPases (SERCA 2a) were quantified by western blot. The responses of cardiomyocytes to UII were also evaluated after pretreatment with the CaMKII inhibitor, KN-93. These results showed that UII increased cell size, protein/DNA ratio and intracellular Ca(2+), consistent with a hypertrophic response. Furthermore, the phosphorylation of CaMKII and its downstream target PLN (Thr17), SERCA 2a levels were up-regulated by UII treatment. Conversely, treatment with KN-93 reversed all those effects of UII. Taken together, the results suggest that UII can induce cardiomyocyte hypertrophy through CaMKII-mediated up-regulating of PLN Thr17-phosphorylation signaling pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Planar polarization of Vangl2 in the vertebrate neural plate is controlled by Wnt and Myosin II signaling

    Directory of Open Access Journals (Sweden)

    Olga Ossipova

    2015-07-01

    Full Text Available The vertebrate neural tube forms as a result of complex morphogenetic movements, which require the functions of several core planar cell polarity (PCP proteins, including Vangl2 and Prickle. Despite the importance of these proteins for neurulation, their subcellular localization and the mode of action have remained largely unknown. Here we describe the anteroposterior planar cell polarity (AP-PCP of the cells in the Xenopus neural plate. At the neural midline, the Vangl2 protein is enriched at anterior cell edges and that this localization is directed by Prickle, a Vangl2-interacting protein. Our further analysis is consistent with the model, in which Vangl2 AP-PCP is established in the neural plate as a consequence of Wnt-dependent phosphorylation. Additionally, we uncover feedback regulation of Vangl2 polarity by Myosin II, reiterating a role for mechanical forces in PCP. These observations indicate that both Wnt signaling and Myosin II activity regulate cell polarity and cell behaviors during vertebrate neurulation.

  15. Reciprocal Roles of Angiotensin II and Angiotensin II Receptors Blockade (ARB in Regulating Cbfa1/RANKL via cAMP Signaling Pathway: Possible Mechanism for Hypertension-Related Osteoporosis and Antagonistic Effect of ARB on Hypertension-Related Osteoporosis

    Directory of Open Access Journals (Sweden)

    Ji-Yao Li

    2011-06-01

    Full Text Available Hypertension is a risk factor for osteoporosis. Animal and epidemiological studies demonstrate that high blood pressure is associated with increased calcium loss, elevated parathyroid hormone, and increased calcium movement from bone. However, the mechanism responsible for hypertension-related osteoporosis remains elusive. Recent epidemiological studies indicate the benefits of Angiotensin II Receptors Blockade (ARB on decreasing fracture risks. Since receptors for angiotensin II, the targets of ARB, are expressed in both osteoblasts and osteoclasts, we postulated that angiotensin II plays an important role in hypertension-related osteoporosis. Cbfa1 and RANKL, the important factors for maintaining bone homeostasis and key mediators in controlling osteoblast and osteoclast differentiation, are both regulated by cAMP-dependent signaling. Angiotensin II along with factors such as LDL, HDL, NO and homocysteine that are commonly altered both in hypertension and osteoporosis, can down-regulate the expression of Cbfa1 but up-regulate RANKL expression via the cAMP signaling pathway. We thus hypothesized that, by altering the ratio of Cbfa1/RANKL expression via the cAMP-dependent pathway, angiotensin II differently regulates osteoblast and osteoclast differentiation leading to enhanced bone resorption and reduced bone formation. Since ARB can antagonize the adverse effect of angiotensin II on bone by lowering cAMP levels and modifying other downstream targets, including LDL, HDL, NO and Cbfa1/RANKL, we propose the hypothesis that the antagonistic effects of ARB may also be exerted via cAMP signaling pathway.

  16. Activation of Rac1 by paxillin-Crk-DOCK180 signaling complex is antagonized by Rap1 in migrating NBT-II cells.

    Science.gov (United States)

    Vallés, Ana M; Beuvin, Maud; Boyer, Brigitte

    2004-10-22

    Induction of epithelial cell motility is a fundamental morphogenetic event that is recapitulated during carcinoma metastasis. Random motility of NBT-II carcinoma cells on collagen critically depends on paxillin phosphorylation at Tyr-31 and Tyr-118, the binding sites for the adapter protein CrkII. Two constitutive partners of CrkII are the exchange factors DOCK180 and C3G. CrkII bound to DOCK180 formed a signaling complex with phosphorylated paxillin that was necessary for cell migration as inferred from the inhibition caused by a DOCK180-interfering mutant. DOCK180, which acts predominantly on the Rho family GTPase Rac1, restored cell locomotion in cells expressing Phe-31/118 paxillin mutants deficient in Rac1 GTP-loading, suggesting that formation of paxillin-Crk-DOCK180 signaling complex controls collagen-dependent migration mainly through Rac1 activation. In migrating cells, CrkII constitutive association with C3G was not sufficient to stimulate its GDP/GTP exchange activity toward the Ras family GTPase Rap1. However, when constitutively active RapV12 was overexpressed, it negatively regulated cell motility. Activation of the C3G/Rap1 signaling pathway resulted in down-regulation of the paxillin-Crk-DOCK180 complex and reduction of Rac1-GTP, suggesting that Rap1 activation could suppress the Rac1 signaling pathway in epithelial cells.

  17. Effects of Wenxin Keli on Cardiac Hypertrophy and Arrhythmia via Regulation of the Calcium/Calmodulin Dependent Kinase II Signaling Pathway

    Science.gov (United States)

    Yang, Xinyu; Chen, Yu; Li, Yanda; Ren, Xiaomeng

    2017-01-01

    We investigated the effects of Wenxin Keli (WXKL) on the Calcium/Calmodulin dependent kinase II (CaMK II) signal transduction pathway with transverse aortic constriction (TAC) rats. Echocardiographic measurements were obtained 3 and 9 weeks after the surgery. Meanwhile, the action potentials (APDs) were recorded using the whole-cell patch clamp technique, and western blotting was used to assess components of the CaMK II signal transduction pathway. At both 3 and 9 weeks after treatment, the fractional shortening (FS%) increased in the WXKL group compared with the TAC group. The APD90 of the TAC group was longer than that of the Sham group and was markedly shortened by WXKL treatment. Western blotting results showed that the protein expressions of CaMK II, phospholamban (PLB), and ryanodine receptor 2 (RYR2) were not statistically significant among the different groups at both treatment time points. However, WXKL treatment decreased the protein level and phosphorylation of CaMK II (Thr-286) and increased the protein level and phosphorylation of PLB (Thr-17) and the phosphorylation of RYR2 (Ser-2814). WXKL also decreased the accumulation of type III collagen fibers. In conclusion, WXKL may improve cardiac function and inhibit the arrhythmia by regulating the CaMK II signal transduction pathway. PMID:28573136

  18. Effects of Wenxin Keli on Cardiac Hypertrophy and Arrhythmia via Regulation of the Calcium/Calmodulin Dependent Kinase II Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xinyu Yang

    2017-01-01

    Full Text Available We investigated the effects of Wenxin Keli (WXKL on the Calcium/Calmodulin dependent kinase II (CaMK II signal transduction pathway with transverse aortic constriction (TAC rats. Echocardiographic measurements were obtained 3 and 9 weeks after the surgery. Meanwhile, the action potentials (APDs were recorded using the whole-cell patch clamp technique, and western blotting was used to assess components of the CaMK II signal transduction pathway. At both 3 and 9 weeks after treatment, the fractional shortening (FS% increased in the WXKL group compared with the TAC group. The APD90 of the TAC group was longer than that of the Sham group and was markedly shortened by WXKL treatment. Western blotting results showed that the protein expressions of CaMK II, phospholamban (PLB, and ryanodine receptor 2 (RYR2 were not statistically significant among the different groups at both treatment time points. However, WXKL treatment decreased the protein level and phosphorylation of CaMK II (Thr-286 and increased the protein level and phosphorylation of PLB (Thr-17 and the phosphorylation of RYR2 (Ser-2814. WXKL also decreased the accumulation of type III collagen fibers. In conclusion, WXKL may improve cardiac function and inhibit the arrhythmia by regulating the CaMK II signal transduction pathway.

  19. Gas6-Axl signaling in presence of Sunitinib is enhanced, diversified and sustained in renal tumor cells, resulting in tumor-progressive advantages.

    Science.gov (United States)

    Gustafsson, Anna; Fritz, Helena K M; Dahlbäck, Björn

    2017-06-01

    Clear Cell Renal Cell Carcinoma (CCRCC) is a lethal cancer with bad prognosis due to development of chemoresistance and recurrence of more aggressive tumors. Investigation of Gas6-mediated Axl signaling in CCRCC and endothelial cells reveals a Sunitinib resistant Gas6-Axl signaling that is sustained and enhanced and specifically triggers downstream AKT and PRAS40 activation in an intensified manner. Gas6-induced Axl signaling in presence of Sunitinib is also diversified displaying onset of Axl-dependent EGFR and METR activation and activation of classical MAPK pathways. Gas6+Sunitinib-adapted CCRCC cells present increased viability and decreased apoptosis and enhanced production of the multi-tumorigenic Osteopontin (OPN) and of one of its activator matrix metalloproteinase-7. Axl activity is necessary for CCRCC cell sphere formation and the ability of the cells to attach after non-adhesive growth. In addition, Gas6+Sunitinib-adapted CCRCC cells displayed enhanced migration and sphere formation, both mechanisms being Axl and OPN dependent. Altogether, this suggests that Sunitinib while targeting endothelial cells and tumor angiogenesis, simultaneously provides protumorigenic effects due to a constitutively, intensified and divergent Gas6-Axl system. Gas6-mediated Axl signaling, which is enhanced and diversified in the presence of Sunitinib possibly contributes to acquired chemoresistance, recurrence of aggressive disease and metastasis of CCRCC tumors. Therefore, combinatorial Axl-targeted therapy might be beneficial for CCRCC patients intended for Sunitinib treatment. Copyright © 2017. Published by Elsevier Inc.

  20. Human T lymphotropic virus type-1 p30II alters cellular gene expression to selectively enhance signaling pathways that activate T lymphocytes

    Directory of Open Access Journals (Sweden)

    Feuer Gerold

    2004-11-01

    Full Text Available Abstract Background Human T-lymphotropic virus type-1 (HTLV-1 is a deltaretrovirus that causes adult T-cell leukemia/lymphoma and is implicated in a variety of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13II and p30II, which are incompletely defined in the virus life cycle or HTLV-1 pathogenesis. Proviral clones of the virus with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. Exogenous expression of p30II differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and represses tax/rex RNA nuclear export. Results Herein, we further characterized the role of p30II in regulation of cellular gene expression, using stable p30II expression system employing lentiviral vectors to test cellular gene expression with Affymetrix U133A arrays, representing ~33,000 human genes. Reporter assays in Jurkat T cells and RT-PCR in Jurkat and primary CD4+ T-lymphocytes were used to confirm selected gene expression patterns. Our data reveals alterations of interrelated pathways of cell proliferation, T-cell signaling, apoptosis and cell cycle in p30II expressing Jurkat T cells. In all categories, p30II appeared to be an overall repressor of cellular gene expression, while selectively increasing the expression of certain key regulatory genes. Conclusions We are the first to demonstrate that p30II, while repressing the expression of many genes, selectively activates key gene pathways involved in T-cell signaling/activation. Collectively, our data suggests that this complex retrovirus, associated with lymphoproliferative diseases, relies upon accessory gene products to modify cellular environment to promote clonal expansion of the virus genome and thus maintain proviral loads in vivo.

  1. Angiotensin II-dependent hypertension requires cyclooxygenase 1-derived prostaglandin E2 and EP1 receptor signaling in the subfornical organ of the brain.

    Science.gov (United States)

    Cao, Xian; Peterson, Jeffrey R; Wang, Gang; Anrather, Josef; Young, Colin N; Guruju, Mallikarjuna R; Burmeister, Melissa A; Iadecola, Costantino; Davisson, Robin L

    2012-04-01

    Cyclooxygenase (COX)-derived prostanoids have long been implicated in blood pressure (BP) regulation. Recently prostaglandin E(2) (PGE(2)) and its receptor EP(1) (EP(1)R) have emerged as key players in angiotensin II (Ang II)-dependent hypertension (HTN) and related end-organ damage. However, the enzymatic source of PGE(2,) that is, COX-1 or COX-2, and its site(s) of action are not known. The subfornical organ (SFO) is a key forebrain region that mediates systemic Ang II-dependent HTN via reactive oxygen species (ROS). We tested the hypothesis that cross-talk between PGE(2)/EP(1)R and ROS signaling in the SFO is required for Ang II HTN. Radiotelemetric assessment of blood pressure revealed that HTN induced by infusion of systemic "slow-pressor" doses of Ang II was abolished in mice with null mutations in EP(1)R or COX-1 but not COX-2. Slow-pressor Ang II-evoked HTN and ROS formation in the SFO were prevented when the EP(1)R antagonist SC-51089 was infused directly into brains of wild-type mice, and Ang-II-induced ROS production was blunted in cells dissociated from SFO of EP(1)R(-/-) and COX-1(-/-) but not COX-2(-/-) mice. In addition, slow-pressor Ang II infusion caused a ≈3-fold increase in PGE(2) levels in the SFO but not in other brain regions. Finally, genetic reconstitution of EP(1)R selectively in the SFO of EP(1)R-null mice was sufficient to rescue slow-pressor Ang II-elicited HTN and ROS formation in the SFO of this model. Thus, COX 1-derived PGE(2) signaling through EP(1)R in the SFO is required for the ROS-mediated HTN induced by systemic infusion of Ang II and suggests that EP(1)R in the SFO may provide a novel target for antihypertensive therapy.

  2. PIK3CA-mutated melanoma cells rely on cooperative signaling through mTORC1/2 for sustained proliferation.

    Science.gov (United States)

    Silva, Jillian M; Deuker, Marian M; Baguley, Bruce C; McMahon, Martin

    2017-05-01

    Malignant conversion of BRAF- or NRAS-mutated melanocytes into melanoma cells can be promoted by PI3'-lipid signaling. However, the mechanism by which PI3'-lipid signaling cooperates with mutationally activated BRAF or NRAS has not been adequately explored. Using human NRAS- or BRAF-mutated melanoma cells that co-express mutationally activated PIK3CA, we explored the contribution of PI3'-lipid signaling to cell proliferation. Despite mutational activation of PIK3CA, melanoma cells were more sensitive to the biochemical and antiproliferative effects of broader spectrum PI3K inhibitors than to an α-selective PI3K inhibitor. Combined pharmacological inhibition of MEK1/2 and PI3K signaling elicited more potent antiproliferative effects and greater inhibition of the cell division cycle compared to single-agent inhibition of either pathway alone. Analysis of signaling downstream of MEK1/2 or PI3K revealed that these pathways cooperate to regulate cell proliferation through mTORC1-mediated effects on ribosomal protein S6 and 4E-BP1 phosphorylation in an AKT-dependent manner. Although PI3K inhibition resulted in cytostatic effects on xenografted NRASQ61H /PIK3CAH1047R melanoma, combined inhibition of MEK1/2 plus PI3K elicited significant melanoma regression. This study provides insights as to how mutationally activated PIK3CA acts in concert with MEK1/2 signaling to cooperatively regulate mTORC1/2 to sustain PIK3CA-mutated melanoma proliferation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Sustained Interleukin-1β Exposure Modulates Multiple Steps in Glucocorticoid Receptor Signaling, Promoting Split-Resistance to the Transactivation of Prominent Anti-Inflammatory Genes by Glucocorticoids

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    Pedro Escoll

    2015-01-01

    Full Text Available Clinical treatment with glucocorticoids (GC can be complicated by cytokine-induced glucocorticoid low-responsiveness (GC-resistance, GCR, a condition associated with a homogeneous reduction in the expression of GC-receptor- (GR- driven anti-inflammatory genes. However, GR level and phosphorylation changes modify the expression of individual GR-responsive genes differently. As sustained IL-1β exposure is key in the pathogenesis of several major diseases with prevalent GCR, we examined GR signaling and the mRNA expression of six GR-driven genes in cells cultured in IL-1β and afterwards challenged with GC. After a GC challenge, sustained IL-1β exposure reduced the cytoplasmic GR level, GRSer203 and GRSer211 phosphorylation, and GR nuclear translocation and led to selective GCR in the expression of the studied genes. Compared to GC alone, in a broad range of GC doses plus sustained IL-1β, FKBP51 mRNA expression was reduced by 1/3, TTP by 2/3, and IRF8 was completely knocked down. In contrast, high GC doses did not change the expression of GILZ and DUSP1, while IGFBP1 was increased by 5-fold. These effects were cytokine-selective, IL-1β dose- and IL-1R1-dependent. The integrated gain and loss of gene functions in the “split GCR” model may provide target cells with a survival advantage by conferring resistance to apoptosis, chemotherapy, and GC.

  4. Comprehensive assessment of Kichwa Ecuadorian Amazon communities for the elaboration of the Strategy for Sustainable Development. II . Socioeconomic indicators

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    Ruth Irene Arias Gutiérrez

    2015-03-01

    Full Text Available A social and economical diagnosis was made in the Amazonian Kichwa region (Napo and Pastaza Provinces for the ellaboration of a sustainable development strategy. Six communities from Anzu river valley, on the eastern slopes of the central Andes in Ecuador, were studied. The quantitative methodology consisted in surveying the residents, managers of the six communities and the heads of 64 households, scattered around five rural parishes. The measured social and economic indicators were annual dependence on local forest and cultivated resources in percentage; the indicators of education, health services and housing conditions for a proposed strategy in order to enhance a sustainable local rural development in the Ecuadorian Amazonian indigenous communities under study. Qualitative and quantitative methods were appropriately used. There are high rates of illiteracy in the communities. Kichwa families depend on local resources. The difference between the satisfaction degree of mestizo and Kichwa families is related to its population weight. There are high illiteracy rates in Boayaku, Union de Llandia and 24 de Mayo. Primary education is low in the communities, and secondary education is very low in all communities. A proposed strategy for sustainable agro-ecological community development is made.

  5. Epidermal growth factor signalling controls myosin II planar polarity to orchestrate convergent extension movements during Drosophila tubulogenesis.

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    Aditya Saxena

    2014-12-01

    Full Text Available Most epithelial tubes arise as small buds and elongate by regulated morphogenetic processes including oriented cell division, cell rearrangements, and changes in cell shape. Through live analysis of Drosophila renal tubule morphogenesis we show that tissue elongation results from polarised cell intercalations around the tubule circumference, producing convergent-extension tissue movements. Using genetic techniques, we demonstrate that the vector of cell movement is regulated by localised epidermal growth factor (EGF signalling from the distally placed tip cell lineage, which sets up a distal-to-proximal gradient of pathway activation to planar polarise cells, without the involvement for PCP gene activity. Time-lapse imaging at subcellular resolution shows that the acquisition of planar polarity leads to asymmetric pulsatile Myosin II accumulation in the basal, proximal cortex of tubule cells, resulting in repeated, transient shortening of their circumferential length. This repeated bias in the polarity of cell contraction allows cells to move relative to each other, leading to a reduction in cell number around the lumen and an increase in tubule length. Physiological analysis demonstrates that animals whose tubules fail to elongate exhibit abnormal excretory function, defective osmoregulation, and lethality.

  6. Resveratrol inhibits Hexokinases II mediated glycolysis in non-small cell lung cancer via targeting Akt signaling pathway.

    Science.gov (United States)

    Li, Wei; Ma, Xiaoqian; Li, Na; Liu, Huasheng; Dong, Qiong; Zhang, Juan; Yang, Cejun; Liu, Yin; Liang, Qi; Zhang, Shengwang; Xu, Chang; Song, Wei; Tan, Shiming; Rong, Pengfei; Wang, Wei

    2016-12-10

    Deregulation of glycolysis was often observed in human cancer cells. In the present study, we reported resveratrol, a small polyphenol, which has been intensively studied in various tumor models, has a profound anti-tumor effect on human non-small cell lung cancer (NSCLC) via regulation of glycolysis. Resveratrol impaired hexokinase II (HK2)-mediated glycolysis, and markedly inhibited anchorage-dependent and -independent growth of NSCLC cells. Exposure to resveratrol decreased EGFR and downstream kinases Akt and ERK1/2 activation. Moreover, we revealed that resveratrol impaired glucose metabolism by mainly inhibiting expression of HK2 mediated by the Akt signaling pathway, and exogenous overexpression of constitutively activated Akt1 in NSCLC cells substantially rescued resveratrol-induced glycolysis suppression. The in vivo data indicated that resveratrol obviously suppressed tumor growth in a xenograft mouse model. Our results suggest targeting HK2 or metabolic enzymes appears to be a new approach for clinical NSCLC prevention or treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Regulation of Ca2+/Calmodulin-Dependent Protein Kinase II Signaling within Hippocampal Glutamatergic Postsynapses during Flurazepam Withdrawal

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    Damien E. Earl

    2012-01-01

    Full Text Available Cessation of one-week oral administration of the benzodiazepine flurazepam (FZP to rats results in withdrawal anxiety after 1 day of withdrawal. FZP withdrawal is correlated with synaptic incorporation of homomeric GluA1-containing α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs in the proximal stratum radiatum of CA1 neurons. After 2 days of withdrawal, Ca2+/calmodulin-dependent protein kinase II (CaMKII phosphorylates GluA1 subunits at Ser831, increasing channel conductance. Secondary to AMPAR potentiation, GluN2B-containing N-methyl-D-aspartate receptors (NMDARs, known binding partners of CaMKII, are selectively removed from the postsynaptic density (PSD. While activation of synaptic CaMKII is known to involve translocation to the PSD, CaMKII bound to NMDARs may be removed from the PSD. To distinguish these possibilities, the current studies used postembedding immunogold electron microscopy to investigate alterations in CaMKII signaling at CA1 stratum radiatum synapses after 2 days of FZP withdrawal. These studies revealed decreased total, but not autophosphorylated (Thr286 CaMKIIα expression in CA1 PSDs. The removal of CaMKII-GluN2B complexes from the PSD during drug withdrawal may serve as a homeostatic mechanism to limit AMPAR-mediated CA1 neuron hyperexcitability and benzodiazepine withdrawal anxiety.

  8. Ang II-AT2R increases mesenchymal stem cell migration by signaling through the FAK and RhoA/Cdc42 pathways in vitro.

    Science.gov (United States)

    Xu, Xiu-Ping; He, Hong-Li; Hu, Shu-Ling; Han, Ji-Bin; Huang, Li-Li; Xu, Jing-Yuan; Xie, Jian-Feng; Liu, Ai-Ran; Yang, Yi; Qiu, Hai-Bo

    2017-07-12

    Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury and are possibly attracted by inflammatory factors. As a proinflammatory mediator, angiotensin II (Ang II) reportedly enhances the migration of various cell types by signaling via the Ang II receptor in vitro. However, few studies have focused on the effects of Ang II on MSC migration and the underlying mechanisms. Human bone marrow MSCs migration was measured using wound healing and Boyden chamber migration assays after treatments with different concentrations of Ang II, an AT1R antagonist (Losartan), and/or an AT2R antagonist (PD-123319). To exclude the effect of proliferation on MSC migration, we measured MSC proliferation after stimulation with the same concentration of Ang II. Additionally, we employed the focal adhesion kinase (FAK) inhibitor PF-573228, RhoA inhibitor C3 transferase, Rac1 inhibitor NSC23766, or Cdc42 inhibitor ML141 to investigate the role of cell adhesion proteins and the Rho-GTPase protein family (RhoA, Rac1, and Cdc42) in Ang II-mediated MSC migration. Cell adhesion proteins (FAK, Talin, and Vinculin) were detected by western blot analysis. The Rho-GTPase family protein activities were assessed by G-LISA and F-actin levels, which reflect actin cytoskeletal organization, were detected by using immunofluorescence. Human bone marrow MSCs constitutively expressed AT1R and AT2R. Additionally, Ang II increased MSC migration in an AT2R-dependent manner. Notably, Ang II-enhanced migration was not mediated by Ang II-mediated cell proliferation. Interestingly, Ang II-enhanced migration was mediated by FAK activation, which was critical for the formation of focal contacts, as evidenced by increased Talin and Vinculin expression. Moreover, RhoA and Cdc42 were activated by FAK to increase cytoskeletal organization, thus promoting cell contraction. Furthermore, FAK, Talin, and Vinculin activation and F-actin reorganization in response to Ang II were prevented by PD-123319 but

  9. Sustained in vivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells

    Science.gov (United States)

    Bell, Charles J.M.; Sun, Yongliang; Nowak, Urszula M.; Clark, Jan; Howlett, Sarah; Pekalski, Marcin L.; Yang, Xin; Ast, Oliver; Waldhauer, Inja; Freimoser-Grundschober, Anne; Moessner, Ekkehard; Umana, Pablo; Klein, Christian; Hosse, Ralf J.; Wicker, Linda S.; Peterson, Laurence B.

    2015-01-01

    Regulatory T cells (Tregs) expressing FOXP3 are essential for the maintenance of self-tolerance and are deficient in many common autoimmune diseases. Immune tolerance is maintained in part by IL-2 and deficiencies in the IL-2 pathway cause reduced Treg function and an increased risk of autoimmunity. Recent studies expanding Tregs in vivo with low-dose IL-2 achieved major clinical successes highlighting the potential to optimize this pleiotropic cytokine for inflammatory and autoimmune disease indications. Here we compare the clinically approved IL-2 molecule, Proleukin, with two engineered IL-2 molecules with long half-lives owing to their fusion in monovalent and bivalent stoichiometry to a non-FcRγ binding human IgG1. Using nonhuman primates, we demonstrate that single ultra-low doses of IL-2 fusion proteins induce a prolonged state of in vivo activation that increases Tregs for an extended period of time similar to multiple-dose Proleukin. One of the common pleiotropic effects of high dose IL-2 treatment, eosinophilia, is eliminated at doses of the IL-2 fusion proteins that greatly expand Tregs. The long half-lives of the IL-2 fusion proteins facilitated a detailed characterization of an IL-2 dose response driving Treg expansion that correlates with increasingly sustained, suprathreshold pSTAT5a induction and subsequent sustained increases in the expression of CD25, FOXP3 and Ki-67 with retention of Treg-specific epigenetic signatures at FOXP3 and CTLA4. PMID:25457307

  10. NO reversibly reduces the water-oxidizing complex of photosystem II through S0 and S-1 to the state characterized by the Mn(II)-Mn(III) multiline EPR signal.

    Science.gov (United States)

    Ioannidis, N; Sarrou, J; Schansker, G; Petrouleas, V

    1998-11-24

    Incubation of photosystem II preparations with NO at -30 degreesC results in the slow formation of a unique state of the water-oxidizing complex (WOC), which was recently identified as a Mn(II)-Mn(III) dimer [Sarrou, J., Ioannidis, N., Deligiannakis, Y., and Petrouleas, V. (1998) Biochemistry 37, 3581-3587]. Evolution of the Mn(II)-Mn(III) EPR signal proceeds through one or more intermediates [Goussias, C., Ioannidis, N., and Petrouleas, V. (1997) Biochemistry 36, 9261-9266]. In an effort to identify these intermediates, we have examined the time course of the signal evolution in the presence and absence of methanol. An early step of the interaction of NO with the WOC is the reduction of S1 to the S0 state, characterized by the weak Mn-hyperfine structure recently reported for that state. At longer times S0 is further reduced to a state which has the properties of the S-1 state, in that single-turnover illumination restores the S0 signal. The Mn(II)-Mn(III) state forms after the S-1 state and is tentatively assigned to an (iso)S-2 state, although lower states or a modified S-1 state cannot be excluded at present. Following removal of NO 60-65% of the initial S2 multiline signal size or the O2-evolving activity can be restored. The data provide for the first time EPR information on a state lower than S0. Furthermore, the low-temperature NO treatment provides a simple means for the selective population of the S0, S-1 and the Mn(II)-Mn(III) states.

  11. Activation of Transcription Factor Nrf2 Signalling by the Sphingosine Kinase Inhibitor SKI-II Is Mediated by the Formation of Keap1 Dimers

    Science.gov (United States)

    Mercado, Nicolas; Kizawa, Yasuo; Ueda, Keitaro; Xiong, Yeping; Kimura, Genki; Moses, Audric; Curtis, Jonathan M.; Ito, Kazuhiro; Barnes, Peter J.

    2014-01-01

    Background Anti-oxidant capacity is crucial defence against environmental or endogenous oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that plays a key defensive role against oxidative and cytotoxic stress and cellular senescence. However, Nrf2 signalling is impaired in several aging-related diseases, such as chronic pulmonary obstructive disease (COPD), cancer, and neurodegenerative diseases. Thus, novel therapeutics that enhance Nrf2 signalling are an attractive approach to treat these diseases. Methodology/Principal Findings Nrf2 was stabilized by SKI-II (2-(p-hydroxyanilino)-4-(p-chlorophenyl) thiazole), which is a known sphingosine kinase inhibitor, in human bronchial epithelial cell line, BEAS2B, and in primary human bronchial epithelial cells, leading to enhancement of anti-oxidant proteins, such as HO-1, NQO1 and GCLM. The activation of Nrf2 was achieved by the generation of inactive dimerized form of Keap1, a negative regulator of Nrf2 expression, which was independent of sphingosine kinase inhibition. Using mice that were exposed to cigarette smoke, SKI-II induced Nrf2 expression together with HO-1 in their lungs. In addition, SKI-II reduced cigarette smoke mediated oxidative stress, macrophages and neutrophil infiltration and markers of inflammation in mice. Conclusions/Significance SKI-II appears to be a novel activator of Nrf2 signalling via the inactivation of Keap1. PMID:24505412

  12. Mutations in the VLGR1 Gene Implicate G-Protein Signaling in the Pathogenesis of Usher Syndrome Type II

    Science.gov (United States)

    Weston, Michael D.; Luijendijk, Mirjam W. J.; Humphrey, Kurt D.; Möller, Claes; Kimberling, William J.

    2004-01-01

    Usher syndrome type II (USH2) is a genetically heterogeneous autosomal recessive disorder with at least three genetic subtypes (USH2A, USH2B, and USH2C) and is classified phenotypically as congenital hearing loss and progressive retinitis pigmentosa. The VLGR1 (MASS1) gene in the 5q14.3-q21.1 USH2C locus was considered a likely candidate on the basis of its protein motif structure and expressed-sequence-tag representation from both cochlear and retinal subtracted libraries. Denaturing high-performance liquid chromatography and direct sequencing of polymerase-chain-reaction products amplified from 10 genetically independent patients with USH2C and 156 other patients with USH2 identified four isoform-specific VLGR1 mutations (Q2301X, I2906FS, M2931FS, and T6244X) from three families with USH2C, as well as two sporadic cases. All patients with VLGR1 mutations are female, a significant deviation from random expectations. The ligand(s) for the VLGR1 protein is unknown, but on the basis of its potential extracellular and intracellular protein-protein interaction domains and its wide mRNA expression profile, it is probable that VLGR1 serves diverse cellular and signaling processes. VLGR1 mutations have been previously identified in both humans and mice and are associated with a reflex-seizure phenotype in both species. The identification of additional VLGR1 mutations to test whether a phenotype/genotype correlation exists, akin to that shown for other Usher syndrome disease genes, is warranted. PMID:14740321

  13. Nitric oxide signaling is recruited as a compensatory mechanism for sustaining synaptic plasticity in Alzheimer's disease mice.

    Science.gov (United States)

    Chakroborty, Shreaya; Kim, Joyce; Schneider, Corinne; West, Anthony R; Stutzmann, Grace E

    2015-04-29

    Synaptic plasticity deficits are increasingly recognized as causing the memory impairments which define Alzheimer's disease (AD). In AD mouse models, evidence of abnormal synaptic function is present before the onset of cognitive deficits, and presents as increased synaptic depression revealed only when synaptic homeostasis is challenged, such as with suppression of ryanodine receptor (RyR)-evoked calcium signaling. Otherwise, at early disease stages, the synaptic physiology phenotype appears normal. This suggests compensatory mechanisms are recruited to maintain a functionally normal net output of the hippocampal circuit. A candidate calcium-regulated synaptic modulator is nitric oxide (NO), which acts presynaptically to boost vesicle release and glutamatergic transmission. Here we tested whether there is a feedforward cycle between the increased RyR calcium release seen in presymptomatic AD mice and aberrant NO signaling which augments synaptic plasticity. Using a combination of electrophysiological approaches, two-photon calcium imaging, and protein biochemistry in hippocampal tissue from presymptomatic 3xTg-AD and NonTg mice, we show that blocking NO synthesis results in markedly augmented synaptic depression mediated through presynaptic mechanisms in 3xTg-AD mice. Additionally, blocking NO reduces the augmented synaptically evoked dendritic calcium release mediated by enhanced RyR calcium release. This is accompanied by increased nNOS levels in the AD mice and is reversed upon normalization of RyR-evoked calcium release with chronic dantrolene treatment. Thus, recruitment of NO is serving a compensatory role to boost synaptic transmission and plasticity during early AD stages. However, NO's dual role in neuroprotection and neurodegeneration may convert to maladaptive functions as the disease progresses. Copyright © 2015 the authors 0270-6474/15/356893-10$15.00/0.

  14. Angiotensin-II-dependent Hypertension Requires Cyclooxygenase 1-derived Prostaglandin E2 and EP1 Receptor Signaling in the Subfornical Organ of the Brain

    Science.gov (United States)

    Cao, Xian; Peterson, Jeffrey R.; Wang, Gang; Anrather, Josef; Young, Colin N.; Guruju, Mallikarjuna R.; Burmeister, Melissa A.; Iadecola, Costantino; Davisson, Robin L.

    2012-01-01

    Cyclooxygenase (COX)-derived prostanoids have long been implicated in blood pressure (BP) regulation. Recently prostaglandin E2 (PGE2) and its receptor EP1R have emerged as key players in angiotensin II (Ang-II)-dependent hypertension (HTN) and related end-organ damage. However, the enzymatic source of PGE2, ie COX-1 or COX-2, and its site(s) of action are not known. The subfornical organ (SFO) is a key forebrain region that mediates systemic Ang-II-dependent HTN via reactive oxygen species (ROS). We tested the hypothesis that cross-talk between PGE2/EP1R and ROS signaling in the SFO is required for Ang-II HTN. Radiotelemetric assessment of BP revealed that HTN induced by infusion of systemic “slow-pressor” doses of Ang-II was abolished in mice with null mutations in EP1R or COX-1 but not COX-2. Slow-pressor Ang-II-evoked HTN and ROS formation in the SFO were prevented when the EP1R antagonist SC-51089 was infused directly into brains of wild-type mice, and Ang-II-induced ROS production was blunted in cells dissociated from SFO of EP1R−/− and COX-1−/− but not COX-2−/− mice. In addition, slow-pressor Ang-II infusion caused a ~3-fold increase in PGE2 levels in the SFO but not in other brain regions. Finally, genetic reconstitution of EP1R selectively in the SFO of EP1R-null mice was sufficient to rescue slow-pressor AngII-elicited HTN and ROS formation in the SFO of this model. Thus, COX-1-derived PGE2 signaling through EP1R in the SFO is required for the ROS-mediated HTN induced by systemic infusion of Ang-II, and suggests that EP1R in the SFO may provide a novel target for antihypertensive therapy. PMID:22371360

  15. Angiotensin II Type 1 Receptor Mechanoactivation Involves RGS5 (Regulator of G Protein Signaling 5) in Skeletal Muscle Arteries: Impaired Trafficking of RGS5 in Hypertension.

    Science.gov (United States)

    Hong, Kwangseok; Li, Min; Nourian, Zahra; Meininger, Gerald A; Hill, Michael A

    2017-12-01

    Studies suggest that arteriolar pressure-induced vasoconstriction can be initiated by GPCRs (G protein-coupled receptors), including the AT 1 R (angiotensin II type 1 receptor). This raises the question, are such mechanisms regulated by negative feedback? The present studies examined whether RGS (regulators of G protein signaling) proteins in vascular smooth muscle cells are colocalized with the AT 1 R when activated by mechanical stress or angiotensin II and whether this modulates AT 1 R-mediated vasoconstriction. To determine whether activation of the AT 1 R recruits RGS5, an in situ proximity ligation assay was performed in primary cultures of cremaster muscle arteriolar vascular smooth muscle cells treated with angiotensin II or hypotonic solution in the absence or presence of candesartan (an AT 1 R blocker). Proximity ligation assay results revealed a concentration-dependent increase in trafficking/translocation of RGS5 toward the activated AT 1 R, which was attenuated by candesartan. In intact arterioles, knockdown of RGS5 enhanced constriction to angiotensin II and augmented myogenic responses to increased intraluminal pressure. Myogenic constriction was attenuated to a higher degree by candesartan in RGS5 siRNA-transfected arterioles, consistent with RGS5 contributing to downregulation of AT 1 R-mediated signaling. Further, translocation of RGS5 was impaired in vascular smooth muscle cells of spontaneously hypertensive rats. This is consistent with dysregulated (RGS5-mediated) AT 1 R signaling that could contribute to excessive vasoconstriction in hypertension. In intact vessels, candesartan reduced myogenic vasoconstriction to a greater extent in spontaneously hypertensive rats compared with controls. Collectively, these findings suggest that AT 1 R activation results in translocation of RGS5 toward the plasma membrane, limiting AT 1 R-mediated vasoconstriction through its role in G q/11 protein-dependent signaling. © 2017 American Heart Association, Inc.

  16. Rosiglitazone Inhibits Angiotensin II-Induced Proliferation of Glomerular Mesangial Cells via the Gαq/Plcβ4/TRPC Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Linting Wei

    2017-12-01

    Full Text Available Background/Aims: Mesangial cell proliferation and extracellular matrix accumulation (ECM deposition play an important role in the pathogenesis of glomerulosclerosis. TRPC and PPAR-γ can regulate cell proliferation. Angiotensin II (AngII can induce mesangial cell proliferation and affect TRPC expression. However, the mechanism has not been fully elucidated. This study was designed to investigate the role of TRPC and the effect of rosiglitazone (RSG in the proliferation of rat glomerular mesangial cells (HBZY-1 that were stimulated by AngII and the underlying mechanisms. Methods: Immunofluorescence staining and qRT-PCR were performed to examine the expression levels of TRPCs in HBZY-1. Gene expression levels of TRPC, PPAR-γ, RGS4 (regulators of G protein signaling, the GPCR/Gαq/PLCβ4/TRPC signaling pathway and major downstream molecules (PCNA, SKP2, P21 and P27 were detected by qRT-PCR and western blotting. Additionally, changes in intracellular Ca2+ levels were determined through Fluo-4 Ca2+ imaging, and the cell cycle was analyzed by flow cytometry. Results: Our results found that TRPC1 and 6 were at higher expression levels in HBZY-1 cells. Following AngII stimulation, there were increased levels of TRPC1 and 6, Ca2+ entry, PCNA and SKP2, decreased expression levels of P21 and P27 and a reduced G0/G1 percentage. Silencing TRPC1 and 6 by siRNAs led to decrease in Ca2+ influx, G0/G1 cell cycle arrest and cell proliferation. Notably, PPAR-γ activation by RSG upregulated RGS4 expression, which can interact with the Gαq family to inhibit the Gαq-mediated signaling cascade. The results were similar to silencing TRPC1 and 6 by siRNAs. Conclusion: All these results indicate that RSG could inhibit HBZY-1 cell proliferation via the Gαq/PLCβ4/TRPC signaling pathway.

  17. Three distinct signals can induce class II gene expression in a murine pre-B-cell line.

    OpenAIRE

    Polla, B S; Poljak, A.; Geier, S G; Nathenson, S G; Ohara, J.; Paul, W E; Glimcher, L H

    1986-01-01

    Expression of class II genes of the major histocompatibility complex (MHC) has been studied in an Abelson-murine-leukemia-virus-transformed pre-B-cell line, R8, and its class II molecule (Ia)-negative variant, R8205. These variant cells contained barely detectable levels of RNA specific for all class II genes, including the nonpolymorphic invariant chain gene (Ii), and did not express cell surface Ia. Fusion of this murine Ia-negative cell line to the human Ia-positive Raji cell produced an i...

  18. Dietary nitrate improves age-related hypertension and metabolic abnormalities in rats via modulation of angiotensin II receptor signaling and inhibition of superoxide generation

    DEFF Research Database (Denmark)

    Hezel, M.; Peleli, Maria; Liu, M.

    2016-01-01

    glucose tolerance in aged rats, via attenuation of NADPH oxidase activity and ANG II receptor signaling. Dietary nitrate supplementation for two weeks reduced blood pressure (10–15 mmHg) and improved glucose clearance in old, but not in young rats. These favorable effects were associated with increased....... Finally, nitrate treatment in aged rats normalized the gene expression profile of ANG II receptors (AT1A, AT2, AT1A/AT2 ratio) in the renal and cardiovascular systems without altering plasma levels of renin or ANG II. Our results show that boosting the nitrate-nitrite-NO pathway can partly compensate......Advanced age is associated with increased risk for cardiovascular disease and type 2 diabetes. A proposed central event is diminished amounts of nitric oxide (NO) due to reduced generation by endothelial NO synthase (eNOS) and increased oxidative stress. In addition, it is widely accepted...

  19. Extracellular signal regulated kinase and SMAD signaling both mediate the angiotensin II driven progression towards overt heart failure in homozygous TGR(mRen2)27

    NARCIS (Netherlands)

    de Boer, RA; Pokharel, S; Flesch, M; van Kampen, DA; Suurmeijer, AJH; Boomsma, F; van Gilst, WH; van Veldhuisen, DJ; Pinto, YM

    2004-01-01

    Angiotensin (Ang) II is a key player in left ventricular (LV) remodeling and cardiac fibrosis. Its effects are thought to be transferred at least in part by mitogen-activated protein kinases (MAPK), transforming growth factor (TGF) beta(1), and the Smad pathway. In this study we sought to elucidate

  20. CD54/intercellular adhesion molecule 1 and major histocompatibility complex II signaling induces B cells to express interleukin 2 receptors and complements help provided through CD40 ligation

    DEFF Research Database (Denmark)

    Poudrier, J; Owens, T

    1994-01-01

    and MHC II in the presence of IL-5 induced expression of a functional IL-2R on small resting B cells. By contrast CD40 ligation, which induced B cell proliferation, did not induce IL-2 responsiveness. These data show that CD40 ligation is necessary but may not be sufficient for B cell differentiation......We have examined signaling roles for CD54 intercellular adhesion molecule 1 and major histocompatibility complex (MHC) II as contact ligands during T help for B cell activation. We used a T helper 1 (Th1)-dependent helper system that was previously shown to be contact as well as interleukin 2 (IL-2......) dependent to demonstrate the relative roles of CD54, MHC II, and CD40 signaling in the events leading to the induction of B cell proliferation and responsiveness to IL-2. Paraformaldehyde-fixed activated Th1-induced expression of IL-2R alpha, IL-2R beta, and B7, and upregulated MHC II and CD54 on B cells...

  1. Review: Towards the agroecological management of ruminants, pigs and poultry through the development of sustainable breeding programmes. II. Breeding strategies.

    Science.gov (United States)

    Phocas, F; Belloc, C; Bidanel, J; Delaby, L; Dourmad, J Y; Dumont, B; Ezanno, P; Fortun-Lamothe, L; Foucras, G; Frappat, B; González-García, E; Hazard, D; Larzul, C; Lubac, S; Mignon-Grasteau, S; Moreno, C R; Tixier-Boichard, M; Brochard, M

    2016-11-01

    Agroecology uses ecological processes and local resources rather than chemical inputs to develop productive and resilient livestock and crop production systems. In this context, breeding innovations are necessary to obtain animals that are both productive and adapted to a broad range of local contexts and diversity of systems. Breeding strategies to promote agroecological systems are similar for different animal species. However, current practices differ regarding the breeding of ruminants, pigs and poultry. Ruminant breeding is still an open system where farmers continue to choose their own breeds and strategies. Conversely, pig and poultry breeding is more or less the exclusive domain of international breeding companies which supply farmers with hybrid animals. Innovations in breeding strategies must therefore be adapted to the different species. In developed countries, reorienting current breeding programmes seems to be more effective than developing programmes dedicated to agroecological systems that will struggle to be really effective because of the small size of the populations currently concerned by such systems. Particular attention needs to be paid to determining the respective usefulness of cross-breeding v. straight breeding strategies of well-adapted local breeds. While cross-breeding may offer some immediate benefits in terms of improving certain traits that enable the animals to adapt well to local environmental conditions, it may be difficult to sustain these benefits in the longer term and could also induce an important loss of genetic diversity if the initial pure-bred populations are no longer produced. As well as supporting the value of within-breed diversity, we must preserve between-breed diversity in order to maintain numerous options for adaptation to a variety of production environments and contexts. This may involve specific public policies to maintain and characterize local breeds (in terms of both phenotypes and genotypes), which could

  2. Methyl gallate isolated from Spondias pinnata exhibits anticancer activity against human glioblastoma by induction of apoptosis and sustained extracellular signal-regulated kinase 1/2 activation.

    Science.gov (United States)

    Chaudhuri, Dipankar; Ghate, Nikhil Baban; Singh, Sudhir Shankar; Mandal, Nripendranath

    2015-01-01

    Spondias pinnata has been reported for its efficient anticancer effects, but the studies were mostly focused on its extract. Since its bioactive compounds are largely unknown, this study was designed to characterize the lead components present in it and their anticancer activity against human glioblastoma cell line (U87). Major compounds from the ethyl acetate fraction were isolated by column chromatography and their anticancer potentials against U87 cells were evaluated. Furthermore, flow cytometric and immunoblotting analyses were performed to demonstrate the mechanism of apoptosis inducing activity of methyl gallate (MG) against U87 cell line. Four major compounds were isolated from the ethyl acetate fraction. Amongst these, two compounds showed promising activities and with the help of different spectroscopic methods they were identified as gallic acid and MG. Flow cytometric studies revealed that MG-induced apoptosis in U87 cells dose-dependently; the same was confirmed by activation of caspases through cleavage of endogenous substrate poly (adenosine diphosphate-ribose) polymerase. MG treatment also induced the expression of p53 and B-cell lymphoma-2-associated X and cleavage of BH3 interacting-domain with a concomitant decrease in B-cell lymphoma-2 expression. Moreover, MG-induced sustained phosphorylation of extracellular signal-regulated kinase (ERK1/2) in U87 cells with no change in the phosphorylation of other mitogen-activated protein kinases (c-Jun N-terminal of stress-activated protein kinases, p38). MG is a potent antioxidant and it induces sustained ERK1/2 activation and apoptosis in human glioblastoma U87, and provide a rationale for evaluation of MG for other brain carcinoma cell lines for the advancement of glioblastoma therapy.

  3. Low-concentration heparin suppresses ionomycin-activated CAMK-II/EGF receptor- and ERK-mediated signaling in mesangial cells.

    Science.gov (United States)

    Song, Lifang; Xiao, Weiqun; Templeton, Douglas M

    2010-08-01

    Heparin and endogenous heparinoids inhibit the proliferation of smooth muscle cells, including renal mesangial cells; multiple effects on signaling pathways are well established, including effects on PKC, Erk, and CaMK-II. Many studies have used heparin at concentrations of 100 microg/ml or higher, whereas endogenous concentrations of heparinoids are much lower. Here we report the effects of low-concentration (1 microg/ml) heparin on activation of several kinases and subsequent induction of the c-fos gene in mesangial cells in response to the calcium ionophore, ionomycin, in the absence of serum factors. Ionomycin rapidly increases the phosphorylation of CaMK-II (by 30 s), and subsequently of the EGF receptor (EGFR), c-Src, and Erk 1/2. Low-dose heparin suppresses the ionomycin-dependent phosphorylation of EGFR, c-Src, and Erk 1/2, but not of CaMK-II, whereas inhibition of activated CaMK-II reduces phosphorylation of EGFR, c-Src, and Erk. Our data support a mechanism whereby heparin acts at the cell surface to suppress downstream targets of CaMK-II, including EGFR, leading in turn to a decrease in Erk- (but not c-Src-) dependent induction of c-fos.

  4. Role of the PKCβII/JNK signaling pathway in acute glucose fluctuation-induced apoptosis of rat vascular endothelial cells.

    Science.gov (United States)

    Wu, Na; Shen, Haitao; Wang, Yanjun; He, Bing; Zhang, Yongyan; Bai, Yu; Du, Runyu; Du, Qiang; Han, Ping

    2017-08-01

    The purpose of this study was to investigate the mechanism of vascular endothelial cell apoptosis induced by acute blood glucose fluctuation. Thirty rats were assigned to three groups: normal saline (SAL group), constant high glucose (CHG group) and acute blood glucose fluctuation (AFG) group. Other forty rats were assigned to SAL group, AFG group, LY group (PKCβ inhibitor LY333531 was injected intragastrically to the rats who were under acute blood glucose fluctuation) and SP group (JNK inhibitor SP600125 was injected intraperitoneally to the rats who were under acute blood glucose fluctuation). Oxidative stress and inflammatory cytokines were detected. TUNEL was performed to detect apoptosis. Pro-caspase-3, caspase-3 p17, JNK, PKC-βII and insulin signaling-related protein expression were tested by Western blotting. After administration of LY333531, AFG-induced membrane translocation of PKCβII protein was inhibited, but SP600125 failed to affect AFG-induced PKCβII membrane translocation. After administration of LY333531, the AFG-induced increase in JNK activity was significantly compromised. LY333531 inhibited AFG-induced oxidative stress. However, SP600125 only slightly inhibited AFG-induced oxidative stress reaction (P > 0.05). Both LY333531 and SP600125 can reverse AFG-induced endothelial cell apoptosis increase, inflammatory cytokines levels rise and insulin signaling impairment. It is necessary to actively control blood glucose and avoid significant glucose fluctuation. PKCβII/JNK may serve as a target, and inhibitors of PKCβII/JNK may be used to help prevent cardiovascular diseases in patients with poor glucose control or significant glucose fluctuation.

  5. Bud detachment in hydra requires activation of fibroblast growth factor receptor and a Rho–ROCK–myosin II signaling pathway to ensure formation of a basal constriction

    Science.gov (United States)

    Holz, Oliver; Apel, David; Steinmetz, Patrick; Lange, Ellen; Hopfenmüller, Simon; Ohler, Kerstin; Sudhop, Stefanie

    2017-01-01

    Background: Hydra propagates asexually by exporting tissue into a bud, which detaches 4 days later as a fully differentiated young polyp. Prerequisite for detachment is activation of fibroblast growth factor receptor (FGFR) signaling. The mechanism which enables constriction and tissue separation within the monolayered ecto‐ and endodermal epithelia is unknown. Results: Histological sections and staining of F‐actin by phalloidin revealed conspicuous cell shape changes at the bud detachment site indicating a localized generation of mechanical forces and the potential enhancement of secretory functions in ectodermal cells. By gene expression analysis and pharmacological inhibition, we identified a candidate signaling pathway through Rho, ROCK, and myosin II, which controls bud base constriction and rearrangement of the actin cytoskeleton. Specific regional myosin phosphorylation suggests a crucial role of ectodermal cells at the detachment site. Inhibition of FGFR, Rho, ROCK, or myosin II kinase activity is permissive for budding, but represses myosin phosphorylation, rearrangement of F‐actin and constriction. The young polyp remains permanently connected to the parent by a broad tissue bridge. Conclusions: Our data suggest an essential role of FGFR and a Rho‐ROCK‐myosin II pathway in the control of cell shape changes required for bud detachment. Developmental Dynamics 246:502–516, 2017. © 2017 The Authors Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists PMID:28411398

  6. Noise-to-signal transition of a Brownian particle in the cubic potential: II. optical trapping geometry

    Science.gov (United States)

    Zemánek, Pavel; Šiler, Martin; Brzobohatý, Oto; Jákl, Petr; Filip, Radim

    2016-06-01

    The noise-to-signal transitions belong to an exciting group of processes in physics. In Filip and Zemánek (2016, J. Opt. 18 065401) we theoretically analyse the stochastic noise-to-signal transition of overdamped Brownian motion of a particle in the cubic potential. In this part, we propose a feasible experimental setup for a proof-of-principle experiment that uses methods of optical trapping in shaped laser beams which provide cubic and quadratic potentials. Theoretical estimates and results from the numerical simulations indicate that the noise-to-signal transition can be observed under realistic experimental conditions.

  7. Obligatory Role of Intraluminal O2− in Acute Endothelin-1 and Angiotensin II Signaling to Mediate Endothelial Dysfunction and MAPK Activation in Guinea-Pig Hearts

    Directory of Open Access Journals (Sweden)

    Emilia Wojtera

    2014-10-01

    Full Text Available We hypothesized that, due to a cross-talk between cytoplasmic O2−-sources and intraluminally expressed xanthine oxidase (XO, intraluminal O2− is instrumental in mediating intraluminal (endothelial dysfunction and cytosolic (p38 and ERK1/2 MAPKs phosphorylation manifestations of vascular oxidative stress induced by endothelin-1 (ET-1 and angiotensin II (AT-II. Isolated guinea-pig hearts were subjected to 10-min agonist perfusion causing a burst of an intraluminal O2−. ET-1 antagonist, tezosentan, attenuated AT-II-mediated O2−, indicating its partial ET-1 mediation. ET-1 and Ang-T (AT-II + tezosentan triggered intraluminal O2−, endothelial dysfunction, MAPKs and p47phox phosphorylation, and NADPH oxidase (Nox and XO activation. These effects were: (i prevented by blocking PKC (chelerythrine, Nox (apocynin, mitochondrial ATP-dependent K+ channel (5-HD, complex II (TTFA, and XO (allopurinol; (ii mimicked by the activation of Nox (NADH; and mitochondria (diazoxide, 3-NPA and (iii the effects by NADH were prevented by 5-HD, TTFA and chelerythrine, and those by diazoxide and 3-NPA by apocynin and chelerythrine, suggesting that the agonists coactivate Nox and mitochondria, which further amplify their activity via PKC. The effects by ET-1, Ang-T, NADH, diazoxide, and 3-NPA were opposed by blocking intraluminal O2− (SOD and XO, and were mimicked by XO activation (hypoxanthine. Apocynin, TTFA, chelerythrine, and SOD opposed the effects by hypoxanthine. In conclusion, oxidative stress by agonists involves cellular inside-out and outside-in signaling in which Nox-mitochondria-PKC system and XO mutually maintain their activities via the intraluminal O2−.

  8. The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part II: signal transduction.

    Science.gov (United States)

    Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

    2015-02-01

    The unique mechanoelectrochemical environment of cartilage has motivated researchers to investigate the effect of multiple biophysical cues, including mechanical, magnetic, and electrical stimulation, on chondrocyte biology. It is well established that biophysical stimuli promote chondrocyte proliferation, differentiation, and maturation within "biological windows" of defined dose parameters, including mode, frequency, magnitude, and duration of stimuli (see companion review Part I: Cellular Response). However, the underlying molecular mechanisms and signal transduction pathways activated in response to multiple biophysical stimuli remain to be elucidated. Understanding the mechanisms of biophysical signal transduction will deepen knowledge of tissue organogenesis, remodeling, and regeneration and aiding in the treatment of pathologies such as osteoarthritis. Further, this knowledge will provide the tissue engineer with a potent toolset to manipulate and control cell fate and subsequently develop functional replacement cartilage. The aim of this article is to review chondrocyte signal transduction pathways in response to mechanical, magnetic, and electrical cues. Signal transduction does not occur along a single pathway; rather a number of parallel pathways appear to be activated, with calcium signaling apparently common to all three types of stimuli, though there are different modes of activation. Current tissue engineering strategies, such as the development of "smart" functionalized biomaterials that enable the delivery of growth factors or integration of conjugated nanoparticles, may further benefit from targeting known signal transduction pathways in combination with external biophysical cues.

  9. The Carboxy Terminal Region of the Human Cytomegalovirus Immediate Early 1 (IE1 Protein Disrupts Type II Inteferon Signaling

    Directory of Open Access Journals (Sweden)

    Bindu Raghavan

    2014-04-01

    Full Text Available Interferons (IFNs activate the first lines of defense against viruses, and promote innate and adaptive immune responses to viruses. We report that the immediate early 1 (IE1 protein of human cytomegalovirus (HCMV disrupts signaling by IFNγ. The carboxyl-terminal region of IE1 is required for this function. We found no defect in the initial events in IFNγ signaling or in nuclear accumulation of signal transducer and activator of transcription 1 (STAT1 in IE1-expressing cells. Moreover, we did not observe an association between disruption of IFNγ signaling and nuclear domain 10 (ND10 disruption. However, there is reduced binding of STAT1 homodimers to target gamma activated sequence (GAS elements in the presence of IE1. Co-immunoprecipitation studies failed to support a direct interaction between IE1 and STAT1, although these studies revealed that the C-terminal region of IE1 was required for interaction with STAT2. Together, these results indicate that IE1 disrupts IFNγ signaling by interfering with signaling events in the nucleus through a novel mechanism.

  10. Signal-to-noise performance analysis of streak tube imaging lidar systems. II. Theoretical analysis and discussion.

    Science.gov (United States)

    Wu, Lei; Wang, Xiaopeng; Yang, Hongru; Yu, Bing; Chen, Chao; Yang, Bin; Yuan, Liang; Wu, Lipeng; Xue, Zhanli; Li, Gaoping; Wu, Baoning

    2012-12-20

    In the preceding paper (referred to here as paper I), we presented a general signal-to-noise performance analysis of a streak tube imaging lidar (STIL) system within the framework of linear cascaded systems theory. A cascaded model is proposed for characterizing the signal-to-noise performance of a STIL system with an internal or external intensified streak tube receiver. The STIL system can be decomposed into a series of cascaded imaging chains whose signal and noise transfer properties are described by the general (or the spatial-frequency dependent) noise factors (NFs). Equations for the general NFs of the cascaded chains (or the main components) in the STIL system are derived. This work investigates the signal-to-noise performance of an external intensified STIL system. The implementation of the cascaded model for predicting and evaluating the signal-to-noise performance of the external intensified STIL system is described. Some factors that limit the signal-to-noise performance of the external intensified STIL system are analyzed and discussed.

  11. The disintegrin and metalloproteinase ADAM12 contributes to TGF-beta signaling through interaction with the type II receptor

    DEFF Research Database (Denmark)

    Atfi, Azeddine; Dumont, Emmanuelle; Colland, Frédéric

    2007-01-01

    Transforming growth factor-beta (TGF-beta) regulates a wide variety of biological processes through two types of Ser/Thr transmembrane receptors: the TGF-beta type I receptor and the TGF-beta type II receptor (TbetaRII). Upon ligand binding, TGF-beta type I receptor activated by TbetaRII propagat...

  12. 'Big'-insulin-like growth factor-II signaling is an autocrine survival pathway in gastrointestinal stromal tumors.

    NARCIS (Netherlands)

    Rikhof, B.; Graaf, W.T.A. van der; Suurmeijer, A.J.H.; Doorn, J. van; Meersma, G.J.; Groenen, P.J.T.A.; Schuuring, E.M.; Meijer, C.; Jong, S. de

    2012-01-01

    New treatment targets need to be identified in gastrointestinal stromal tumors (GISTs) to extend the treatment options for patients experiencing failure with small-molecule tyrosine kinase inhibitors, such as imatinib. Insulin-like growth factor (IGF)-II acts as an autocrine factor in several tumor

  13. 'Big'-Insulin-Like Growth Factor-II Signaling Is an Autocrine Survival Pathway in Gastrointestinal Stromal Tumors

    NARCIS (Netherlands)

    Rikhof, Bart; van der Graaf, Winette T. A.; Suurmeijer, Albert J. H.; van Doorn, Jaap; Meersma, Gert Jan; Groenen, Patricia J. T. A.; Schuuring, Ed M. D.; Meijer, Coby; de Jong, Steven

    New treatment targets need to be identified in gastrointestinal stromal tumors (GISTs) to extend the treatment options for patients experiencing failure with small-molecule tyrosine kinase inhibitors, such as imatinib. Insulin-like growth factor (IGF)-II acts as an autocrine factor in several tumor

  14. MHC class II molecules deliver costimulatory signals in human T cells through a functional linkage with IL-2-receptors

    DEFF Research Database (Denmark)

    Odum, Niels; Kanner, S B; Ledbetter, J A

    1993-01-01

    a regulatory function in T cell activation. Here, we show that cross-linking HLA-DR and -DP but not -DQ molecules by immobilized mAb enhanced proliferative T cell responses to IL-2. In contrast, class II stimulation had no effect on IL-4-induced proliferation. The costimulatory effect was most pronounced...... at low concentrations of IL-2, was blocked by IL-2R mAb, and was at least partly mediated through an up-regulation of IL-2 high affinity receptors. As expected, activation of IL-2R by IL-2 induced tyrosine phosphorylation of several proteins including p56lck, and class II cross-linking by mAb induced...... tyrosine phosphorylation of specific substrates including PLC-gamma 1. Combined stimulation of IL-2R and class II molecules had an additive effect on tyrosine phosphorylation. Pretreatment of T cells with a protein tyrosine kinase inhibitor, herbimycin A, inhibited IL-2 and class II-induced proliferation...

  15. Angiotensin II signaling increases activity of the renal Na-Cl cotransporter through a WNK4-SPAK-dependent pathway.

    NARCIS (Netherlands)

    San Cristobal, P.; Pacheco-Alvarez, D.; Richardson, C.; Ring, A.M.; Vazquez, N.; Rafiqi, F.H.; Chari, D.; Kahle, K.T.; Leng, Q.; Bobadilla, N.A.; Hebert, S.C.; Alessi, D.R.; Lifton, R.P.; Gamba, G.

    2009-01-01

    Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a syndrome featuring hypertension and high serum K(+) levels (hyperkalemia). WNK4 has distinct functional states that regulate the balance between renal salt reabsorption and K(+) secretion by modulating the activities of

  16. Visual signal detection in structured backgrounds. II. Effects of contrast gain control, background variations, and white noise

    Science.gov (United States)

    Eckstein, M. P.; Ahumada, A. J. Jr; Watson, A. B.

    1997-01-01

    Studies of visual detection of a signal superimposed on one of two identical backgrounds show performance degradation when the background has high contrast and is similar in spatial frequency and/or orientation to the signal. To account for this finding, models include a contrast gain control mechanism that pools activity across spatial frequency, orientation and space to inhibit (divisively) the response of the receptor sensitive to the signal. In tasks in which the observer has to detect a known signal added to one of M different backgrounds grounds due to added visual noise, the main sources of degradation are the stochastic noise in the image and the suboptimal visual processing. We investigate how these two sources of degradation (contrast gain control and variations in the background) interact in a task in which the signal is embedded in one of M locations in a complex spatially varying background (structured background). We use backgrounds extracted from patient digital medical images. To isolate effects of the fixed deterministic background (the contrast gain control) from the effects of the background variations, we conduct detection experiments with three different background conditions: (1) uniform background, (2) a repeated sample of structured background, and (3) different samples of structured background. Results show that human visual detection degrades from the uniform background condition to the repeated background condition and degrades even further in the different backgrounds condition. These results suggest that both the contrast gain control mechanism and the background random variations degrade human performance in detection of a signal in a complex, spatially varying background. A filter model and added white noise are used to generate estimates of sampling efficiencies, an equivalent internal noise, an equivalent contrast-gain-control-induced noise, and an equivalent noise due to the variations in the structured background.

  17. Recovery Of Short Wavelength Geophysical Signals With Future Delay-Doppler Altimeters (Cryosat Ii And Sentinel Type)

    DEFF Research Database (Denmark)

    Andersen, Ole Baltazar

    2010-01-01

    altimetry: Factor of 20 improvements in along track resolution. An along-track footprint length that does not vary with wave height (sea state). Twice the precision in sea surface height measurements / sea surface slope measurements. These improvements are studied with respect to retrieval of short...... wavelength geophysical signal related to mainly bathymetric features. The combination of upward continuation from the sea bottom and smoothing the altimeter observations resulted in the best recovery of geophysical signal for simulated 5-Hz DD observations. Simulations carried out in this investigation...

  18. IcarisideII improves left ventricular remodeling in spontaneously hypertensive rats by inhibiting the ASK1-JNK/p38 signaling pathway.

    Science.gov (United States)

    Wu, Yuting; Qian, Zhiqiang; Fu, Shu; Yue, Yun; Li, Yeli; Sun, Ruimin; Huang, Bo; Yang, Danli

    2017-11-21

    Inhibition or removal of excess reactive oxygen species can effectively protect cellular function or reduce cell death because oxidative stress is the main cause of cellular damage in many diseases. The flavonoid compound IcarisideII having a slight inhibitory effect on PDE5, is the main active components of epimedium in vivo and has a wide range of pharmacological effects on oxidation and apoptosis. However, whether IcarisideII has the same protective effect on ventricular remodeling in spontaneously hypertensive rats (SHR) is unknown. We found that compared with WKY rats, SHRs exhibited noticeable arterial hypertension. Additionally, echocardiography showed that the diameter of the left ventricle was enlarged, wall thickness was increased, and ejection fraction and short axis shortening rate were reduced. H&E staining demonstrated that SHR cells were disordered and noticeably hypertrophic. Masson trichrome staining revealed significant myocardial fibrosis in the myocardium. Tunel staining indicated that 4.39 times the percent of apoptotic cells were present in SHRs compared to WKY rats. In our study, intra-gastric administration of IcarisideII decreased blood pressure, promoted heart function recovery and improved ventricular remodeling in SHRs. Additionally, it reduced myocardial fibrosis, inhibited myocardial apoptosis, decreased the generation of reactive oxygen species and improved SOD activity. IcarisideII down-regulated the activation of the oxidative stress associated proteins ASK1, p38 and JNK; inhibited the expression of p53, Bax and cleaved-caspase3 in the mitochondrial apoptosis pathway; and up-regulated the expression of Bcl-2. In conclusion, this study indicates that IcarisideII can inhibit myocardial apoptosis and improve left ventricular remodeling in SHRs. It can be inferred that this mechanism may be related to the inhibition of the ASK1-JNK/p38 signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Inactivation of TGFβ receptor II signalling in pancreatic epithelial cells promotes acinar cell proliferation, acinar-to-ductal metaplasia and fibrosis during pancreatitis.

    Science.gov (United States)

    Grabliauskaite, Kamile; Saponara, Enrica; Reding, Theresia; Bombardo, Marta; Seleznik, Gitta M; Malagola, Ermanno; Zabel, Anja; Faso, Carmen; Sonda, Sabrina; Graf, Rolf

    2016-02-01

    Determining signalling pathways that regulate pancreatic regeneration following pancreatitis is critical for implementing therapeutic interventions. In this study we elucidated the molecular mechanisms underlying the effects of transforming growth factor-β (TGFβ) in pancreatic epithelial cells during tissue regeneration. To this end, we conditionally inactivated TGFβ receptor II (TGFβ-RII) using a Cre-LoxP system under the control of pancreas transcription factor 1a (PTF1a) promoter, specific for the pancreatic epithelium, and evaluated the molecular and cellular changes in a mouse model of cerulein-induced pancreatitis. We show that TGFβ-RII signalling does not mediate the initial acinar cell damage observed at the onset of pancreatitis. However, TGFβ-RII signalling not only restricts acinar cell replication during the regenerative phase of the disease but also limits ADM formation in vivo and in vitro in a cell-autonomous manner. Analyses of molecular mechanisms underlying the observed phenotype revealed that TGFβ-RII signalling stimulates the expression of cyclin-dependent kinase inhibitors and intersects with the EGFR signalling axis. Finally, TGFβ-RII ablation in epithelial cells resulted in increased infiltration of inflammatory cells in the early phases of pancreatitis and increased activation of pancreatic stellate cells in the later stages of pancreatitis, thus highlighting a TGFβ-based crosstalk between epithelial and stromal cells regulating the development of pancreatic inflammation and fibrosis. Collectively, our data not only contribute to clarifying the cellular processes governing pancreatic tissue regeneration, but also emphasize the conserved role of TGFβ as a tumour suppressor, both in the regenerative process following pancreatitis and in the initial phases of pancreatic cancer. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  20. Signal and binding. II. Converting physico-chemical responses to macromolecule-ligand interactions into thermodynamic binding isotherms.

    Science.gov (United States)

    Bujalowski, Wlodzimierz; Jezewska, Maria J; Bujalowski, Paul J

    2017-03-01

    Physico-chemical titration techniques are the most commonly used methods in characterizing molecular interactions. These methods are mainly based on spectroscopic, calorimetric, hydrodynamic, etc., measurements. However, truly quantitative physico-chemical methods are absolutely based on the determination of the relationship between the measured signal and the total average degree of binding in order to obtain meaningful interaction parameters. The relationship between the observed physico-chemical signal of whatever nature and the degree of binding must be determined and not assumed, based on some ad hoc intuitive relationship/model, leading to determination of the true binding isotherm. The quantitative methods reviewed and discussed here allow an experimenter to rigorously determine the degree of binding and the free ligand concentration, i.e., they lead to the construction of the thermodynamic binding isotherm in a model-independent fashion from physico-chemical titration curves. Copyright © 2016. Published by Elsevier B.V.

  1. Proactive sustainability strategy and corporate sustainability performance: The mediating effect of sustainability control systems.

    Science.gov (United States)

    Wijethilake, Chaminda

    2017-07-01

    This study examines to what extent corporations use sustainability control systems (SCS) to translate proactive sustainability strategy into corporate sustainability performance. The study investigates the mediating effect of SCS on the relationship between proactive sustainability strategy and corporate sustainability performance. Survey data were collected from top managers in 175 multinational and local corporations operating in Sri Lanka and analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). SCS were observed to only partially mediate the relationship between proactive sustainability strategy and corporate sustainability performance. The mediating effect of SCS is further examined under three sustainability strategies; environmental and social strategies reveal a partial mediation, while the economic strategy exhibits no mediation. The study also finds that (i) a proactive sustainability strategy is positively associated with SCS and corporate sustainability performance and (ii) SCS are positively associated with corporate sustainability performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The angiotensin-(1-7/Mas axis counteracts angiotensin II-dependent and –independent pro-inflammatory signaling in human vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Laura A Villalobos

    2016-12-01

    Full Text Available Background and aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7 is a member of the renin-angiotensin system (RAS that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7 to counteract human aortic smooth muscle cell (HASMC inflammation triggered by RAS-dependent and –independent stimuli, such as Ang II or interleukin (IL-1.Methods and Results: In cultured HASMC, the expression of iNOS and the release of nitric oxide were stimulated by both Ang II and IL-1, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7 in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro7-Ang-(1-7, suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and NF-B. Indeed, Ang-(1-7 markedly inhibited the activation of the NADPH oxidase and subsequently of NF-B, as determined by lucigenin-derived chemiluminiscence and electromobility shift assay, respectively.Conclusion: Ang-(1-7 can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases.

  3. The Angiotensin-(1-7)/Mas Axis Counteracts Angiotensin II-Dependent and -Independent Pro-inflammatory Signaling in Human Vascular Smooth Muscle Cells.

    Science.gov (United States)

    Villalobos, Laura A; San Hipólito-Luengo, Álvaro; Ramos-González, Mariella; Cercas, Elena; Vallejo, Susana; Romero, Alejandra; Romacho, Tania; Carraro, Raffaele; Sánchez-Ferrer, Carlos F; Peiró, Concepción

    2016-01-01

    Background and Aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7) is a member of the renin-angiotensin system (RAS) that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7) to counteract human aortic smooth muscle cell (HASMC) inflammation triggered by RAS-dependent and -independent stimuli, such as Ang II or interleukin (IL)-1β. Methods and Results: In cultured HASMC, the expression of inducible nitric oxide synthase (iNOS) and the release of nitric oxide were stimulated by both Ang II and IL-1β, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7) in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro7-Ang-(1-7), suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and nuclear factor (NF)-κB. Indeed, Ang-(1-7) markedly inhibited the activation of the NADPH oxidase and subsequently of NF-κB, as determined by lucigenin-derived chemiluminescence and electromobility shift assay, respectively. Conclusion: Ang-(1-7) can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7)/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases.

  4. Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion

    DEFF Research Database (Denmark)

    Odum, Niels; Yoshizumi, H; Okamoto, Y

    1992-01-01

    Crosslinking HLA-DR molecules by monoclonal antibodies (moAbs) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic calcium concentrations in activated human T cells. Binding of bacterial superantigens or moAbs to DR molecules on activated T cells...... was recently reported to induce homotypic aggregation through activation of protein kinase C (PKC) and mediated by CD11a/CD54 (LFA-1/CAM-1) adhesion molecules. Here, we report that moAbs directed against framework DR, but neither DR1, 2- and DRw52- nor DQ- and DP-specific moABs induced homotypic aggregation...... of antigen- and alloantigen-activated T cells, antigen-specific CD4+ T-cell lines, a CD8+ T-cytotoxic cell line, and T-leukemia cells (HUT78). Protein tyrosine kinase (PTK) inhibitor herbimycin A partly blocked class-II-induced aggregation responses. In contrast, phorbol ester (PMA)-induced aggregation...

  5. Sustainability and Entrepreneurial Action

    DEFF Research Database (Denmark)

    Korsgaard, Steffen T.; Anderson, Alistair

    Abstract Objectives - This paper explores how entrepreneurial action can lead to environmental sustainability. It builds on the assumption that the creation of sustainble practices is one of the most important challenges facing the global society, and that entrepreneurial action is a vital...... instrument in the pursuit of sustainability.  Prior Work - Extant literature identifies two main approaches to sustainable entrepreneurship. (i) traditional exploitation of environmentally relevant opportunities and (ii) institutional entrepreneurship creating opportunities. We identify a novel form......: resource oriented sustainable entrepreneurial action.  Approach - The paper uses a case study approach to build deeper theoretical knowledge of environmentally sustainable entrepreneurship.  Results - The paper identifies and analyses a distinct form of sustainable entrepreneurship -  resource oriented...

  6. Flash-induced relaxation changes of the EPR signals from the manganese cluster and YD reveal a light-adaptation process of photosystem II.

    Science.gov (United States)

    Peterson, Sindra; Ahrling, Karin A; Högblom, Joakim E P; Styring, Stenbjörn

    2003-03-11

    By exposing photosystem II (PSII) samples to an incrementing number of excitation flashes at room temperature, followed by freezing, we could compare the Mn-derived multiline EPR signal from the S2 oxidation state as prepared by 1, 5, 10, and 25 flashes of light. While the S2 multiline signals exhibited by these samples differed very little in spectral shape, a significant increase of the relaxation rate of the signal was detected in the multiflash samples as compared to the S2-state produced by a single oxidation. A similar relaxation rate increase was observed for the EPR signal from Y(D*). The temperature dependence of the multiline spin-lattice relaxation rate is similar after 1 and 5 flashes. These data are discussed together with previously reported phenomena in terms of a light-adaptation process of PSII, which commences on the third flash after dark-adaptation and is completed after 10 flashes. At room temperature, the fast-relaxing, light-adapted state falls back to the slow-relaxing, dark-adapted state with t(1/2) = 80 s. We speculate that light-adaptation involves changes necessary for efficient continuous water splitting. This would parallel activation processes found in many other large redox enzymes, such as Cytochrome c oxidase and Ni-Fe hydrogenase. Several mechanisms of light-adaptation are discussed, and we find that the data may be accounted for by a change of the PSII protein matrix or by the light-induced appearance of a paramagnetic center on the PSII donor side. At this time, no EPR signal has been detected that correlates with the increase of the relaxation rates, and the nature of such a new paramagnet remains unclear. However, the relaxation enhancement data could be used, in conjunction with the known Mn-Y(D) distance, to estimate the position of such an unknown relaxer. If positioned between Y(D) and the Mn cluster, it would be located 7-8 A from the spin center of the S2 multiline signal.

  7. Staphylococcal nuclease domain containing-1 (SND1 promotes migration and invasion via angiotensin II type 1 receptor (AT1R and TGFβ signaling

    Directory of Open Access Journals (Sweden)

    Prasanna K. Santhekadur

    2014-01-01

    Full Text Available Staphylococcal nuclease domain containing-1 (SND1 is overexpressed in human hepatocellular carcinoma (HCC patients and promotes tumorigenesis by human HCC cells. We now document that SND1 increases angiotensin II type 1 receptor (AT1R levels by increasing AT1R mRNA stability. This results in activation of ERK, Smad2 and subsequently the TGFβ signaling pathway, promoting epithelial–mesenchymal transition (EMT and migration and invasion by human HCC cells. A positive correlation was observed between SND1 and AT1R expression levels in human HCC patients. Small molecule inhibitors of SND1, alone or in combination with AT1R blockers, might be an effective therapeutic strategy for late-stage aggressive HCC.

  8. Angiotensin II receptor subtypes are coupled with distinct signal-transduction mechanisms in neurons and astrocytes from rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Sumners, C.; Wei Tang; Zelezna, B.; Raizada, M.K. (Univ. of Florida, Gainesville (United States))

    1991-09-01

    Both neurons and astrocytes contain specific receptors for angiotensin II (AII). The authors used selective ligands for the AT{sub 1} and AT{sub 2} types of AII receptors to investigate the expression of functional receptor subtypes in astrocyte cultures and neuron cultures from 1-day-old (neonatal) rat brain. In astrocyte cultures, competition of {sup 125}I-labeled AII ({sup 125}I-AII) specific binding with AT{sub 1} (DuP753) or AT{sub 2} {l brace}PD123177, CGP42112A, (Phe(p-NH{sub 2}){sup 6})AII{r brace} selective receptor ligands revealed a potency series of AII > DuP753 > > > CGP42112A > (Phe(p-NH{sub 2}){sup 6})AII > PD123177. These results suggest a predominance of the AT{sub 1} receptor subtype in neonatal astrocytes. {sup 125}I-AII specific binding to neonate neuronal cultures was reduced 73-84% by 1 {mu} MPD123177, and the residual {sup 125}I-AII specific binding was eliminated by DuP753. The results suggest that astrocyte cultures from neonatal rat brains contain predominantly AT{sub 1} receptors that are coupled to a stimulation of inositophospholipid hydrolysis. In contrast, neuron cultures from neonatal rat brain contain mostly AT{sub 2} receptors that are coupled to a reduction in basal cGMP levels, but a smaller population of AT{sub 1} receptors is also present in these neurons.

  9. Angiotensin II-AT1–receptor signaling is necessary for cyclooxygenase-2–dependent postnatal nephron generation

    DEFF Research Database (Denmark)

    Frölich, Stefanie; Slattery, Patrick; Thomas, Dominique

    2017-01-01

    Deletion of cyclooxygenase-2 (COX-2) causes impairment of postnatal kidney development. Here we tested whether the renin angiotensin system contributes to COX-2–dependent nephrogenesis in mice after birth and whether a rescue of impaired renal development and function in COX-2-/- mice was achieva......Deletion of cyclooxygenase-2 (COX-2) causes impairment of postnatal kidney development. Here we tested whether the renin angiotensin system contributes to COX-2–dependent nephrogenesis in mice after birth and whether a rescue of impaired renal development and function in COX-2-/- mice...... was achievable. Plasma renin concentration in mouse pups showed a birth peak and a second peak around day P8 during the first 10 days post birth. Administration of the angiotensin II receptor AT1 antagonist telmisartan from day P1 to P3 did not result in cortical damage. However, telmisartan treatment from day P...... development. Inhibition of the renin angiotensin system by aliskiren and enalapril caused similar glomerular defects as telmisartan. Administration of the AT1 receptor agonist L162313 to COX-2-/- pups improved kidney growth, ameliorated renal defects, but had no beneficial effect on reduced cortical mass. L...

  10. [In vitro studies of Raf-CREB, Akt-CREB, and CaMK II -CREB signal transduction pathway regulated by ginsenosides Rb1, Rg1 and Re].

    Science.gov (United States)

    Wang, Ting-Ting; Dong, Xian-Zhe; Liu, Wan-Wan; Chen, Yi-Hong; Liu, Ping

    2014-06-01

    Effects of ginsenoside Rb1, Rg1 and Re on neurotrophic factor signal transduction pathway using liposome-mediated transfection of eukaryotic cells approach. The injury model was established by treating SH-SY5Y cells with 0.6 mmol x L(-1) of corticosterone (CORT) by 24 h. SH-SY5Y cell were pretreated with CORT for 30 min followed by co-treated with 120,60 and 20 micromol x L(-1) of Rb1, 120, 80 and 40 micromol x L(-1) of Rg1 and 120, 80 and 40 micromol x L(-1) of Re for 24 h. Cells viability was determined by Cell Counting Kit (CCK) assay. CREB expressing Luciferase reporter gene was constructed and transfected with plasmid containing hRaf, hcAMP, hAkt, hCaMK gene into human embryonic kidney (HEK293) cells using liposornal transfection reagent lipofection 2000. The expression of CREB before and after it addion of Rb1, Rg1 and Re was examined by Luc assay system and Western blotting. Compared with normal control group, CORT significantly decreased the viability of SH-SY5Y cells to 67.21% (P CaMK II. Rb1, Rg1 and Re protects SH-SY5Y cells from CORT-induced damage and the neuroprotective mechanism may be associated with the Raf-CREB, Akt-CREB and CaMK II -CREB pathways.

  11. Dual sphingosine kinase inhibitor SKI-II enhances sensitivity to 5-fluorouracil in hepatocellular carcinoma cells via suppression of osteopontin and FAK/IGF-1R signalling.

    Science.gov (United States)

    Grbčić, Petra; Tomljanović, Ivana; Klobučar, Marko; Kraljević Pavelić, Sandra; Lučin, Ksenija; Sedić, Mirela

    2017-06-10

    Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related deaths globally. Although 5-Fluorouracil (5-FU) is used as the first choice treatment for advanced HCC, it exerts poor efficacy and is associated with acquired and intrinsic resistance. Sphingosine kinases (Sphk) 1 and 2 play tumour-promoting roles in different cancer types including HCC and thus represent promising pharmacological targets. In the present study, we have investigated for the first time the anticancer efficacy and underlying molecular mechanisms of combined administration of 5-FU and dual Sphk1/Sphk2 inhibitor SKI-II (4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol) in HepG2 hepatocellular carcinoma cells. Here, we report that co-administration of 5-FU and SKI-II at low sub-toxic concentrations of 20 μM and 5 μM, respectively, synergistically inhibit cell proliferation, markedly reduce cell migration and the clonogenic survival, and increase apoptosis induction in HepG2 cells. Additional Western blot analyses have shown that possible mechanisms underlying enhanced sensitivity to 5-FU induced by dual Sphk 1/2 inhibition could include abrogation of FAK-regulated IGF-1R activity and down-regulation of osteopontin expression culminating in the inhibition of NF-κB activity and its downstream signalling mediated by sirtuin 1 and p38 MAPK. Our results clearly show that pharmacological blockade of both Sphk isoforms represents a promising strategy to boost the anti-tumour efficacy of 5-FU and provide a rationale for further in vivo studies into the possible use of SKI-II inhibitor as an adjunct to 5-FU treatment in HCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. NBT-II cell locomotion is modulated by restricting the size of focal contacts and is improved through EGF and ROCK signaling.

    Science.gov (United States)

    Liu, Hong-Wen; Lin, Chia-Ping; Liou, Yi-Jia; Hsu, Kuo-Wei; Yang, Jung-Yen; Lin, Chi-Hung

    2014-06-01

    Focal contacts, large macromolecular complexes that link the extracellular matrix and the internal cell cytoskeleton, are thought to govern cell locomotion. However, the maturation process through which focal contacts control the cellular migratory machinery by changes in size and molecular composition remain unclear. Here, we fabricated cell growth substrates that contained linear ECM strips of micron- or submicron-width in order to limit the enlargement of focal contacts. We found that NBT-II cells plated on the submicron substrate possessed smaller focal complexes that exhibited a highly dynamic turnover. These cells possessed various leading edges at multiple sites of the cell periphery, which prevented the cell from advancing. In contrast, cells grown on the micron-width substrate possessed large and stable focal adhesions. Most of these cells were elongated bipolar cells that were tethered at both ends and were immobile. Further, EGF and ROCK signaling pathways can modulate the cellular migratory responses according to the substrate guidance. On the submicron-width substrate, EGF treatment increased the focal contact size and the contractile force, causing these cells to develop one leading edge and migrate along the submicron-sized ECM paths. In contrast, inhibition of ROCK signaling decreased the focal contact size for cells plated on the micron substrate. These cells became less tethered and were able to migrate along or even across the micron-sized ECM paths. Our results indicate that formation and maturation of focal contacts is controlled by both ECM cues and intracellular signaling and they play a central role in directed cell motion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Dynamic topographical pattern classification of multichannel prefrontal NIRS signals: II. Online differentiation of mental arithmetic and rest

    Science.gov (United States)

    Schudlo, Larissa C.; Chau, Tom

    2014-02-01

    Objective. Near-infrared spectroscopy (NIRS) has recently gained attention as a modality for brain-computer interfaces (BCIs), which may serve as an alternative access pathway for individuals with severe motor impairments. For NIRS-BCIs to be used as a real communication pathway, reliable online operation must be achieved. Yet, only a limited number of studies have been conducted online to date. These few studies were carried out under a synchronous paradigm and did not accommodate an unconstrained resting state, precluding their practical clinical implication. Furthermore, the potentially discriminative power of spatiotemporal characteristics of activation has yet to be considered in an online NIRS system. Approach. In this study, we developed and evaluated an online system-paced NIRS-BCI which was driven by a mental arithmetic activation task and accommodated an unconstrained rest state. With a dual-wavelength, frequency domain near-infrared spectrometer, measurements were acquired over nine sites of the prefrontal cortex, while ten able-bodied participants selected letters from an on-screen scanning keyboard via intentionally controlled brain activity (using mental arithmetic). Participants were provided dynamic NIR topograms as continuous visual feedback of their brain activity as well as binary feedback of the BCI's decision (i.e. if the letter was selected or not). To classify the hemodynamic activity, temporal features extracted from the NIRS signals and spatiotemporal features extracted from the dynamic NIR topograms were used in a majority vote combination of multiple linear classifiers. Main results. An overall online classification accuracy of 77.4 ± 10.5% was achieved across all participants. The binary feedback was found to be very useful during BCI use, while not all participants found value in the continuous feedback provided. Significance. These results demonstrate that mental arithmetic is a potent mental task for driving an online system

  14. Ca2+/Calmodulin-Dependent Protein Kinase II and Androgen Signaling Pathways Modulate MEF2 Activity in Testosterone-Induced Cardiac Myocyte Hypertrophy

    Directory of Open Access Journals (Sweden)

    Javier Duran

    2017-09-01

    Full Text Available Testosterone is known to induce cardiac hypertrophy through androgen receptor (AR-dependent and -independent pathways, but the molecular underpinnings of the androgen action remain poorly understood. Previous work has shown that Ca2+/calmodulin-dependent protein kinase II (CaMKII and myocyte-enhancer factor 2 (MEF2 play key roles in promoting cardiac myocyte growth. In order to gain mechanistic insights into the action of androgens on the heart, we investigated how testosterone affects CaMKII and MEF2 in cardiac myocyte hypertrophy by performing studies on cultured rat cardiac myocytes and hearts obtained from adult male orchiectomized (ORX rats. In cardiac myocytes, MEF2 activity was monitored using a luciferase reporter plasmid, and the effects of CaMKII and AR signaling pathways on MEF2C were examined by using siRNAs and pharmacological inhibitors targeting these two pathways. In the in vivo studies, ORX rats were randomly assigned to groups that were administered vehicle or testosterone (125 mg⋅kg-1⋅week-1 for 5 weeks, and plasma testosterone concentrations were determined using ELISA. Cardiac hypertrophy was evaluated by measuring well-characterized hypertrophy markers. Moreover, western blotting was used to assess CaMKII and phospholamban (PLN phosphorylation, and MEF2C and AR protein levels in extracts of left-ventricle tissue from control and testosterone-treated ORX rats. Whereas testosterone treatment increased the phosphorylation levels of CaMKII (Thr286 and phospholambam (PLN (Thr17 in cardiac myocytes in a time- and concentration-dependent manner, testosterone-induced MEF2 activity and cardiac myocyte hypertrophy were prevented upon inhibition of CaMKII, MEF2C, and AR signaling pathways. Notably, in the hypertrophied hearts obtained from testosterone-administered ORX rats, both CaMKII and PLN phosphorylation levels and AR and MEF2 protein levels were increased. Thus, this study presents the first evidence indicating that

  15. Influence of Genetic Background on Hematologic and Histopathologic Alterations during Acute Granulocytic Anaplasmosis in 129/SvEv and C57BL/6J Mice Lacking Type I and Type II Interferon Signaling.

    Science.gov (United States)

    Johns, Jennifer L; Discipulo, Marielle L; Koehne, Amanda L; Moorhead, Kaitlin A; Nagamine, Claude M

    2017-03-01

    The role of host type I IFN signaling and its interaction with other immune pathways during bacterial infections is incompletely understood. Type II IFN signaling plays a key role during numerous bacterial infections including granulocytic anaplasmosis (GA) caused by Anaplasma phagocytophilum infection. The function of combined type I and type II IFN signaling and their potential synergism during GA and similar tick-borne diseases is a topic of current research investigation. The goal of this study was to evaluate 2 mouse models of absent type I/type II IFN signaling in experimental A. phagocytophilum infection to determine the effects of background strain. Mice lacking both type I and type II IFN receptor signaling (IFNAR-/-/IFNGR-/-) on either the 129/SvEv or C57BL/6J genetic background were evaluated at days 0, 6, 8, and 12 of infection. Pathogen burden in multiple organs was largely similar between strains of infected mice, with few significant differences. Background strain influenced the immune response to infection. Mice of the 129/SvEv strain developed more severe hematologic abnormalities, particularly more severe leukocytosis with marked neutrophilia and lymphocytosis, throughout acute infection. Histopathologic changes occurred in infected mice of both strains and varied in severity by organ. 129/SvEv mice developed more severe pathologic changes in spleen and bone marrow, whereas C57BL/6J mice developed more severe renal pathology. This work highlights the importance of mouse background strain in dictating pathophysiologic response to infection and informs future work regarding the loss of type I and type II IFN signaling on the immune response during GA.

  16. Sustainable Food & Sustainable Economics

    OpenAIRE

    Alvarez, Mavis Dora

    2012-01-01

    Cuba today is immersed in a very intense process of perfecting its agricultural production structures with the goal of making them more efficient and sustainable in their economic administration and in their social and environmental management. Agricultural cooperatives in Cuba have the responsibility of producing on 73% of the country's farmland. Their contributions are decisive to developing agricultural production and to ensuring more and better food for the population, in addition to redu...

  17. The impact of the conversion of incandescent bulbs to the LED light source in traffic signals in Houston : a step toward sustainable control devices.

    Science.gov (United States)

    2015-06-01

    With the slowing of the American economy since 2008, it has become imperative that municipalities : identify areas in which costs can be reduced while still providing needed services to its constituents. The : use of traffic signals equipped with lig...

  18. Augmented sphingosine 1 phosphate receptor-1 signaling in cardiac fibroblasts induces cardiac hypertrophy and fibrosis through angiotensin II and interleukin-6

    Science.gov (United States)

    Ohkura, Sei-ichiro; Takashima, Shin-ichiro; Yoshioka, Kazuaki; Okamoto, Yasuo; Inagaki, Yutaka; Sugimoto, Naotoshi; Kitano, Teppei; Takamura, Masayuki; Wada, Takashi; Kaneko, Shuichi; Takuwa, Yoh

    2017-01-01

    Background: Cardiac fibroblasts, together with cardiomyocytes, occupy the majority of cells in the myocardium and are involved in myocardial remodeling. The lysophospholipid mediator sphigosine-1-phosphate (S1P) regulates functions of cardiovascular cells through multiple receptors including S1PR1–S1PR3. S1PR1 but not other S1P receptors was upregulated in angiotensin II-induced hypertrophic hearts. Therefore, we investigated a role of S1PR1 in fibroblasts for cardiac remodeling by employing transgenic mice that overexpressed S1PR1 under the control of α-smooth muscle actin promoter. In S1PR1-transgenic mouse heart, fibroblasts and/or myofibroblasts were hyperplastic, and those cells as well as vascular smooth muscle cells overexpressed S1PR1. Transgenic mice developed bi-ventricular hypertrophy by 12-week-old and diffuse interstitial fibrosis by 24-week-old without hemodynamic stress. Cardiac remodeling in transgenic mice was associated with greater ERK phosphorylation, upregulation of fetal genes, and systolic dysfunction. Transgenic mouse heart showed increased mRNA expression of angiotensin-converting enzyme and interleukin-6 (IL-6). Isolated fibroblasts from transgenic mice exhibited enhanced generation of angiotensin II, which in turn stimulated IL-6 release. Either an AT1 blocker or angiotensin-converting enzyme inhibitor prevented development of cardiac hypertrophy and fibrosis, systolic dysfunction and increased IL-6 expression in transgenic mice. Finally, administration of anti-IL-6 antibody abolished an increase in tyrosine phosphorylation of STAT3, a major signaling molecule downstream of IL-6, in the transgenic mouse heart and prevented development of cardiac hypertrophy in transgenic mice. These results demonstrate a promoting role of S1PR1 in cardiac fibroblasts for cardiac remodeling, in which angiotensin II—AT1 and IL-6 are involved. PMID:28771545

  19. Mechanisms involving Ang II and MAPK/ERK1/2 signaling pathways underlie cardiac and renal alterations during chronic undernutrition.

    Directory of Open Access Journals (Sweden)

    Paulo A Silva

    Full Text Available Several studies have correlated protein restriction associated with other nutritional deficiencies with the development of cardiovascular and renal diseases. The driving hypothesis for this study was that Ang II signaling pathways in the heart and kidney are affected by chronic protein, mineral and vitamin restriction.Wistar rats aged 90 days were fed from weaning with either a control or a deficient diet that mimics those used in impoverished regions worldwide. Such restriction simultaneously increased ouabain-insensitive Na+-ATPase and decreased (Na++K+ATPase activity in the same proportion in cardiomyocytes and proximal tubule cells. Type 1 angiotensin II receptor (AT1R was downregulated by that restriction in both organs, whereas AT2R decreased only in the kidney. The PKC/PKA ratio increased in both tissues and returned to normal values in rats receiving Losartan daily from weaning. Inhibition of the MAPK pathway restored Na+-ATPase activity in both organs. The undernourished rats presented expanded plasma volume, increased heart rate, cardiac hypertrophy, and elevated systolic pressure, which also returned to control levels with Losartan. Such restriction led to electrical cardiac remodeling represented by prolonged ventricular repolarization parameters, induced triggered activity, early after-depolarization and delayed after-depolarization, which were also prevented by Losartan.The mechanisms responsible for these alterations are underpinned by an imbalance in the PKC- and PKA-mediated pathways, with participation of angiotensin receptors and by activation of the MAPK/ERK1/2 pathway. These cellular and molecular alterations culminate in cardiac electric remodeling and in the onset of hypertension in adulthood.

  20. Serotonin regulates 6-phosphofructo-1-kinase activity in a PLC-PKC-CaMK II- and Janus kinase-dependent signaling pathway.

    Science.gov (United States)

    Coelho, Wagner Santos; Sola-Penna, Mauro

    2013-01-01

    Serotonin (5-HT) is a hormone that has been implicated in the regulation of many physiological and pathological events. One of the most intriguing properties of this hormone is its ability to up-regulate mitosis. Moreover, 5-HT stimulates glucose uptake and up-regulates PFK activity through the 5-HT(2A) receptor, resulting in the phosphorylation of a tyrosine residue of PFK and the intracellular redistribution of PFK within skeletal muscle. The present study investigated some of the signaling intermediates involved in the effects of 5-HT on 6-phosphofructo-1-kinase (PFK) regulation from skeletal muscle using kinetic assessments, immunoprecipitation, and western blotting assays. Our results demonstrate that 5-HT stimulates PFK from skeletal muscle via phospholipase C (PLC). The activation of PLC in skeletal muscle leads to the recruitment of protein kinase C (PKC) and calmodulin and the stimulation of calmodulin kinase II, which associates with PFK upon 5-HT action. Alternatively, 5-HT loses its ability to up-regulate PFK activity when Janus kinase is inhibited, suggesting that 5-HT is able to control glycolytic flux in the skeletal muscle of mice by recruiting different pathways and controlling PFK activity.

  1. Quantitative proteome analysis of alveolar type-II cells reveals a connection of integrin receptor subunits beta 2/6 and WNT signaling.

    Science.gov (United States)

    Mukhametshina, Regina T; Ruhs, Aaron; Singh, Indrabahadur; Hasan, Diya; Contreras, Adriana; Mehta, Aditi; Nikam, Vandana S; Ahlbrecht, Katrin; Carraro, Gianni; Cabrera-Fuentes, Hector A; Jiang, Dongsheng; Voswinckel, Robert; Seeger, Werner; Bellusci, Saverio; Scharffetter-Kochanek, Karin; Bagaeva, Tatyana V; Preissner, Klaus T; Boettger, Thomas; Braun, Thomas; Krüger, Marcus; Barreto, Guillermo

    2013-12-06

    Alveolar type-II cells (ATII cells) are lung progenitor cells responsible for regeneration of alveolar epithelium during homeostatic turnover and in response to injury. Characterization of ATII cells will have a profound impact on our understanding and treatment of lung disease. The identification of novel ATII cell-surface proteins can be used for sorting and enrichment of these cells for further characterization. Here we combined a high-resolution mass spectrometry-based membrane proteomic approach using lungs of the SILAC mice with an Affymetrix microarray-based transcriptome analysis of ATII cells. We identified 16 proteins that are enriched in the membrane fraction of ATII cells and whose genes are highly expressed in these cells. Interestingly, we confirmed our data for two of these genes, integrin beta 2 and 6 (Itgb2 and Itgb6), by qRT-PCR expression analysis and Western blot analysis of protein extracts. Moreover, flow cytometry and immunohistochemistry in adult lung revealed that ITGB2 and ITGB6 are present in subpopulations of surfactant-associated-protein-C-positive cells, suggesting the existence of different types of ATII cells. Furthermore, analysis of the Itgb2(-/-) mice showed that Itgb2 is required for proper WNT signaling regulation in the lung.

  2. Phytantriol and glyceryl monooleate cubic liquid crystalline phases as sustained-release oral drug delivery systems for poorly water-soluble drugs II. In-vivo evaluation.

    Science.gov (United States)

    Nguyen, Tri-Hung; Hanley, Tracey; Porter, Christopher J H; Larson, Ian; Boyd, Ben J

    2010-07-01

    Lipid-based liquid crystals formed from phytantriol (PHY) and glyceryl monooleate (GMO) retain their cubic-phase structure on dilution in physiologically relevant simulated gastrointestinal media, suggesting their potential application as sustained-release drug-delivery systems for poorly water-soluble drugs. In this study the potential of PHY and GMO to serve as sustained-release lipid vehicles for a model poorly-water-soluble drug, cinnarizine, was assessed and compared to that of an aqueous suspension formulation. Small-angle X-ray scattering was used to confirm the nanostructure of the liquid-crystalline matrix in the presence of the selected model drug, cinnarizine. Oral bioavailability studies were conducted in rats, and disposition of lipid and drug in segments of the gastrointestinal tract was determined over time. Differences in the digestibility and stability of formulations under digestion conditions were investigated using an in-vitro lipolysis model. The oral bioavailability of cinnarizine using the PHY formulation was 41%, compared to 19% for the GMO formulation and 6% for an aqueous suspension. The PHY formulation provided a T(max) for cinnarizine of 33 h, with absorption apparent up to 55 h after administration. In contrast, the T(max) for the GMO formulation was only 5 h. The PHY formulation was retained in the stomach for extended periods of time, with 56% of lipid remaining in the stomach after 24 h, in contrast to less than 1% of the GMO formulation after 8 h, suggesting that gastric retention was a key aspect of the prolonged period of absorption, which correlated with the formulations' relative susceptibility to in-vitro lipolysis and degradation. PHY provides a dramatic sustained-release effect for cinnarizine on oral administration, which is linked to gastric retention of the formulation and its ability to resist digestive processing. Poorly digested liquid crystal lipid formulations therefore offer a novel class of sustained

  3. Food miles to assess sustainability: A revision

    OpenAIRE

    Van Passel, Steven

    2013-01-01

    Sustainability assessment is an essential process in our aim to reach a more sustainable production and consumption pattern. This research revises the food miles concept as a guiding tool to assess sustainability. Food miles measure the distance that food travels from where it is grown or raised to where it is consumed. Three different concepts to assess sustainability are described: (i) food miles, (ii) enhanced food miles, (iii) food chain sustainability. An illustrative case study shows th...

  4. Sustainable Scientists

    Energy Technology Data Exchange (ETDEWEB)

    Mills, Evan

    2008-12-31

    Scientists are front and center in quantifying and solving environmental problems. Yet, as a spate of recent news articles in scientific journals point out, much can be done to enhance sustainability within the scientific enterprise itself, particularly by trimming the energy use associated with research facilities and the equipment therein (i,ii,iii, iv). Sponsors of research unwittingly spend on the order of $10 billion each year on energy in the U.S. alone, and the underlying inefficiencies drain funds from the research enterprise while causing 80 MT CO2-equivalent greenhouse-gas emissions (see Box). These are significant sums considering the opportunity costs in terms of the amount of additional research that could be funded and emissions that could be reduced if the underlying energy was used more efficiently. By following commercially proven best practices in facility design and operation, scientists--and the sponsors of science--can cost-effectively halve these costs, while doing their part to put society on alow-carbon diet.

  5. [Intervention of Qi-activating and Spleen-strengthening Herbs on Ca2+/CaMK II Signaling Pathways Key Factors in Skeletal Muscle Tissue of Rats with Spleen-qi Deficiency].

    Science.gov (United States)

    Duan, Yong-qiang; Cheng, Ying-xia; Liang, Yu-jie; Cheng, Wei-dong; Du, Juan; Yang, Xiao-yi; Wang, Yan

    2015-03-01

    To observe changes of [Ca2+]i concentration and CaM, CaMK II and p-CaMK II of Ca2+/CaMK II signaling pathways in skeletal muscle tissue of rats with spleen-qi deficiency and intervention of Sijunzi decoction and extract of Hedysarum polybotrys. Rats were randomized into four groups: normal control group, spleen-qi deficient model group, extract from Hedysarum polybotrys group and Sijunzi decoction group, ten rats in each group. After the spleen-qi deficient models were built by comprehensive application of rhubarb, exhaustive and hungry methods, and treatment groups were treated with extract from Hedysarum polybotrys at 6 g/(kg . d) or Sijunzi decoction at 20 g/(kg . d) for 21 d. Then, general existence,gastrointestinal hormones GAS and MOT levels, and activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase of skeletal muscle were evaluated. Also, confocal laser technology was used to test cellular[Ca2+]i concentrations in skeletal muscle and Western blotting technique was used to test CaM, CaMK II and p-CaMK 11 expression in intestinal tissue of spleen-qi deficient model rats. Compared with normal group, general condition was poor, levels of GAS and MOT decreased (P CaMK II and p-CaMK II in skeletal muscle decreased significantly (P CaMK II in skeletal muscle tissue increased (P CaMK II in skeletal muscle tissue increased in the rats of Sijunzi decoction group (P < 0. 05). Sijunzi decoction and extract of Hedysarum polybotrys can be applied to treat spleen-qi deficiency syndrome through the mechanism of regulating GAS and MOT secretion and raising expression of Ca2+ /CaM signaling pathways key factors in skeletal muscle tissue. Sijunzi decoction has the better effect

  6. APLICAÇÃO DE IMAGENS IKONOS II E TM/LANDSAT-5 NA ELABORAÇÃO DE UMA BASE CARTOGRÁFICA PARA A RESERVA DE DESENVOLVIMENTO SUSTENTÁVEL MAMIRAUÁ – AMAZONAS / APPLICATION OF IKONOS II AND TM/LANDSAT-5 SATELLITES DATA FOR DIGITAL BASE MAPPING THE SUSTAINABLE DEVELOPMENT RESERVE MAMIRAUÁ, AMAZON, BRAZIL

    Directory of Open Access Journals (Sweden)

    Josimara Martins Dias

    2009-12-01

    Full Text Available This paper has as purpose present the methodology developed to produce an updated digital map base support for participatory management Mamirauá Reserve of Sustainable Development in the state of Amazonas, Braszil. Because this protected área is situated within an area of flooded forest, both the physical landscape and social organization often change, and the dynamic demand the systematic update of cartographic databases. This work has images of orbital sensors IKONOS II and LANDSAT 5 TM, interviews with users and collecting spatial data in the Mamirauá Reserve. This work obtained a cartographic base at 1:100.000 scale and a geodatabase compatible with the local references, with which is possible to generate thematic maps updated to support dialogue in the sustainable management programs of the Mamirauá Reserve and minimize conflicts with communities.

  7. Differential Regulation of Smad3 and of the Type II Transforming Growth Factor-β Receptor in Mitosis: Implications for Signaling

    Science.gov (United States)

    Hirschhorn, Tal; Barizilay, Lior; Smorodinsky, Nechama I.; Ehrlich, Marcelo

    2012-01-01

    The response to transforming growth factor-β (TGF-β) depends on cellular context. This context is changed in mitosis through selective inhibition of vesicle trafficking, reduction in cell volume and the activation of mitotic kinases. We hypothesized that these alterations in cell context may induce a differential regulation of Smads and TGF-β receptors. We tested this hypothesis in mesenchymal-like ovarian cancer cells, arrested (or not) in mitosis with 2-methoxyestradiol (2ME2). In mitosis, without TGF-β stimulation, Smad3 was phosphorylated at the C-terminus and linker regions and localized to the mitotic spindle. Phosphorylated Smad3 interacted with the negative regulators of Smad signaling, Smurf2 and Ski, and failed to induce a transcriptional response. Moreover, in cells arrested in mitosis, Smad3 levels were progressively reduced. These phosphorylations and reduction in the levels of Smad3 depended on ERK activation and Mps1 kinase activity, and were abrogated by increasing the volume of cells arrested in mitosis with hypotonic medium. Furthermore, an Mps1-dependent phosphorylation of GFP-Smad3 was also observed upon its over-expression in interphase cells, suggesting a mechanism of negative regulation which counters increases in Smad3 concentration. Arrest in mitosis also induced a block in the clathrin-mediated endocytosis of the type II TGF-β receptor (TβRII). Moreover, following the stimulation of mitotic cells with TGF-β, the proteasome-mediated attenuation of TGF-β receptor activity, the degradation and clearance of TβRII from the plasma membrane, and the clearance of the TGF-β ligand from the medium were compromised, and the C-terminus phosphorylation of Smad3 was prolonged. We propose that the reduction in Smad3 levels, its linker phosphorylation, and its association with negative regulators (observed in mitosis prior to ligand stimulation) represent a signal attenuating mechanism. This mechanism is balanced by the retention of active TGF

  8. Differential regulation of Smad3 and of the type II transforming growth factor-β receptor in mitosis: implications for signaling.

    Directory of Open Access Journals (Sweden)

    Tal Hirschhorn

    Full Text Available The response to transforming growth factor-β (TGF-β depends on cellular context. This context is changed in mitosis through selective inhibition of vesicle trafficking, reduction in cell volume and the activation of mitotic kinases. We hypothesized that these alterations in cell context may induce a differential regulation of Smads and TGF-β receptors. We tested this hypothesis in mesenchymal-like ovarian cancer cells, arrested (or not in mitosis with 2-methoxyestradiol (2ME2. In mitosis, without TGF-β stimulation, Smad3 was phosphorylated at the C-terminus and linker regions and localized to the mitotic spindle. Phosphorylated Smad3 interacted with the negative regulators of Smad signaling, Smurf2 and Ski, and failed to induce a transcriptional response. Moreover, in cells arrested in mitosis, Smad3 levels were progressively reduced. These phosphorylations and reduction in the levels of Smad3 depended on ERK activation and Mps1 kinase activity, and were abrogated by increasing the volume of cells arrested in mitosis with hypotonic medium. Furthermore, an Mps1-dependent phosphorylation of GFP-Smad3 was also observed upon its over-expression in interphase cells, suggesting a mechanism of negative regulation which counters increases in Smad3 concentration. Arrest in mitosis also induced a block in the clathrin-mediated endocytosis of the type II TGF-β receptor (TβRII. Moreover, following the stimulation of mitotic cells with TGF-β, the proteasome-mediated attenuation of TGF-β receptor activity, the degradation and clearance of TβRII from the plasma membrane, and the clearance of the TGF-β ligand from the medium were compromised, and the C-terminus phosphorylation of Smad3 was prolonged. We propose that the reduction in Smad3 levels, its linker phosphorylation, and its association with negative regulators (observed in mitosis prior to ligand stimulation represent a signal attenuating mechanism. This mechanism is balanced by the retention

  9. Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8+ T lymphocytes.

    Science.gov (United States)

    Papadakis, Konstantinos A; Krempski, James; Reiter, Jesse; Svingen, Phyllis; Xiong, Yuning; Sarmento, Olga F; Huseby, April; Johnson, Aaron J; Lomberk, Gwen A; Urrutia, Raul A; Faubion, William A

    2015-03-01

    KLF10 has recently elicited significant attention as a transcriptional regulator of transforming growth factor-β1 (TGF-β1) signaling in CD4(+) T cells. In the current study, we demonstrate a novel role for KLF10 in the regulation of TGF-β receptor II (TGF-βRII) expression with functional relevance in antiviral immune response. Specifically, we show that KLF10-deficient mice have an increased number of effector/memory CD8(+) T cells, display higher levels of the T helper type 1 cell-associated transcription factor T-bet, and produce more IFN-γ following in vitro stimulation. In addition, KLF10(-/-) CD8(+) T cells show enhanced proliferation in vitro and homeostatic proliferation in vivo. Freshly isolated CD8(+) T cells from the spleen of adult mice express lower levels of surface TGF-βRII (TβRII). Congruently, in vitro activation of KLF10-deficient CD8(+) T cells upregulate TGF-βRII to a lesser extent compared with wild-type (WT) CD8(+) T cells, which results in attenuated Smad2 phosphorylation following TGF-β1 stimulation compared with WT CD8(+) T cells. Moreover, we demonstrate that KLF10 directly binds to the TGF-βRII promoter in T cells, leading to enhanced gene expression. In vivo viral infection with Daniel's strain Theiler's murine encephalomyelitis virus (TMEV) also led to lower expression of TGF-βRII among viral-specific KLF10(-/-) CD8(+) T cells and a higher percentage of IFN-γ-producing CD8(+) T cells in the spleen. Collectively, our data reveal a critical role for KLF10 in the transcriptional activation of TGF-βRII in CD8(+) T cells. Thus, KLF10 regulation of TGF-βRII in this cell subset may likely play a critical role in viral and tumor immune responses for which the integrity of the TGF-β1/TGF-βRII signaling pathway is crucial. Copyright © 2015 the American Physiological Society.

  10. A cleavable signal peptide enhances cell surface delivery and heterodimerization of Cerulean-tagged angiotensin II AT1 and bradykinin B2 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Quitterer, Ursula, E-mail: ursula.quitterer@pharma.ethz.ch [Molecular Pharmacology Unit, Swiss Federal Institute of Technology and University of Zurich, Zurich (Switzerland); Pohl, Armin; Langer, Andreas; Koller, Samuel; AbdAlla, Said [Molecular Pharmacology Unit, Swiss Federal Institute of Technology and University of Zurich, Zurich (Switzerland)

    2011-06-10

    Highlights: {yields} A new FRET-based method detects AT1/B2 receptor heterodimerization. {yields} First time application of AT1-Cerulean as a FRET donor. {yields} Method relies on signal peptide-enhanced cell surface delivery of AT1-Cerulean. {yields} A high FRET efficiency revealed efficient heterodimerization of AT1/B2R proteins. {yields} AT1/B2R heterodimers were functionally coupled to desensitization mechanisms. -- Abstract: Heterodimerization of the angiotensin II AT1 receptor with the receptor for the vasodepressor bradykinin, B2R, is known to sensitize the AT1-stimulated response of hypertensive individuals in vivo. To analyze features of that prototypic receptor heterodimer in vitro, we established a new method that uses fluorescence resonance energy transfer (FRET) and applies for the first time AT1-Cerulean as a FRET donor. The Cerulean variant of the green fluorescent protein as donor fluorophore was fused to the C-terminus of AT1, and the enhanced yellow fluorescent protein (EYFP) as acceptor fluorophore was fused to B2R. In contrast to AT1-EGFP, the AT1-Cerulean fusion protein was retained intracellularly. To facilitate cell surface delivery of AT1-Cerulean, a cleavable signal sequence was fused to the receptor's amino terminus. The plasma membrane-localized AT1-Cerulean resembled the native AT1 receptor regarding ligand binding and receptor activation. A high FRET efficiency of 24.7% between membrane-localized AT1-Cerulean and B2R-EYFP was observed with intact, non-stimulated cells. Confocal FRET microscopy further revealed that the AT1/B2 receptor heterodimer was functionally coupled to receptor desensitization mechanisms because activation of the AT1-Cerulean/B2R-EYFP heterodimer with a single agonist triggered the co-internalization of AT1/B2R. Receptor co-internalization was sensitive to inhibition of G protein-coupled receptor kinases, GRKs, as evidenced by a GRK-specific peptide inhibitor. In agreement with efficient AT1/B2R

  11. Sustainable agriculture

    National Research Council Canada - National Science Library

    Lichtfouse, Eric

    2009-01-01

    ... : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : 9 Part I CLIMATE CHANGE Soils and Sustainable Agriculture: A Review : : : : : : : : : : : : : : : : : : : : : : : : : : Rattan Lal 15 Soils and Food Sufficiency...

  12. Insulin/IGF-1 signaling, including class II/III PI3Ks, β-arrestin and SGK-1, is required in C. elegans to maintain pharyngeal muscle performance during starvation.

    Science.gov (United States)

    Dwyer, Donard S; Aamodt, Eric J

    2013-01-01

    In C. elegans, pharyngeal pumping is regulated by the presence of bacteria. In response to food deprivation, the pumping rate rapidly declines by about 50-60%, but then recovers gradually to baseline levels on food after 24 hr. We used this system to study the role of insulin/IGF-1 signaling (IIS) in the recovery of pharyngeal pumping during starvation. Mutant strains with reduced function in the insulin/IGF-1 receptor, DAF-2, various insulins (INS-1 and INS-18), and molecules that regulate insulin release (UNC-64 and NCA-1; NCA-2) failed to recover normal pumping rates after food deprivation. Similarly, reduction or loss of function in downstream signaling molecules (e.g., ARR-1, AKT-1, and SGK-1) and effectors (e.g., CCA-1 and UNC-68) impaired pumping recovery. Pharmacological studies with kinase and metabolic inhibitors implicated class II/III phosphatidylinositol 3-kinases (PI3Ks) and glucose metabolism in the recovery response. Interestingly, both over- and under-activity in IIS was associated with poorer recovery kinetics. Taken together, the data suggest that optimum levels of IIS are required to maintain high levels of pharyngeal pumping during starvation. This work may ultimately provide insights into the connections between IIS, nutritional status and sarcopenia, a hallmark feature of aging in muscle.

  13. Insulin/IGF-1 signaling, including class II/III PI3Ks, β-arrestin and SGK-1, is required in C. elegans to maintain pharyngeal muscle performance during starvation.

    Directory of Open Access Journals (Sweden)

    Donard S Dwyer

    Full Text Available In C. elegans, pharyngeal pumping is regulated by the presence of bacteria. In response to food deprivation, the pumping rate rapidly declines by about 50-60%, but then recovers gradually to baseline levels on food after 24 hr. We used this system to study the role of insulin/IGF-1 signaling (IIS in the recovery of pharyngeal pumping during starvation. Mutant strains with reduced function in the insulin/IGF-1 receptor, DAF-2, various insulins (INS-1 and INS-18, and molecules that regulate insulin release (UNC-64 and NCA-1; NCA-2 failed to recover normal pumping rates after food deprivation. Similarly, reduction or loss of function in downstream signaling molecules (e.g., ARR-1, AKT-1, and SGK-1 and effectors (e.g., CCA-1 and UNC-68 impaired pumping recovery. Pharmacological studies with kinase and metabolic inhibitors implicated class II/III phosphatidylinositol 3-kinases (PI3Ks and glucose metabolism in the recovery response. Interestingly, both over- and under-activity in IIS was associated with poorer recovery kinetics. Taken together, the data suggest that optimum levels of IIS are required to maintain high levels of pharyngeal pumping during starvation. This work may ultimately provide insights into the connections between IIS, nutritional status and sarcopenia, a hallmark feature of aging in muscle.

  14. Sustainable Marketing

    NARCIS (Netherlands)

    Dam, van Y.K.

    2017-01-01

    In this article, three different conceptions of sustainable marketing are discussed and compared. These different conceptions are referred to as social, green, and critical sustainable marketing. Social sustainable marketing follows the logic of demand-driven marketing management and places the

  15. Optimization of the signal selection of exclusively reconstructed decays of B0 and B/s mesons at CDF-II

    Energy Technology Data Exchange (ETDEWEB)

    Doerr, Christian [Univ. of Karlsruhe (Germany)

    2006-06-23

    The work presented in this thesis is mainly focused on the application in a Δms measurement. Chapter 1 starts with a general theoretical introduction on the unitarity triangle with a focus on the impact of a Δms measurement. Chapter 2 then describes the experimental setup, consisting of the Tevatron collider and the CDF II detector, that was used to collect the data. In chapter 3 the concept of parameter estimation using binned and unbinned maximum likelihood fits is laid out. In addition an introduction to the NeuroBayes{reg_sign} neural network package is given. Chapter 4 outlines the analysis steps walking the path from the trigger level selection to fully reconstructed B mesons candidates. In chapter 5 the concepts and formulas that form the ingredients to an unbinned maximum likelihood fit of Δms (Δmd) from a sample of reconstructed B mesons are discussed. Chapter 6 then introduces the novel method of using neural networks to achieve an improved signal selection. First the method is developed, tested and validated using the decay B0 → Dπ, D → Kππ and then applied to the kinematically very similar decay Bs → Dsπ, Ds→ Φπ, Φ → KK. Chapter 7 uses events selected by the neural network selection as input to an unbinned maximum likelihood fit and extracts the B0 lifetime and Δmd. In addition, an amplitude scan and an unbinned maximum likelihood fit of Δms is performed, applying the neural network selection developed for the decay channel Bs → Dsπ, Ds → Φπ, Φ → KK. Finally chapter 8 summarizes and gives an outlook.

  16. The Peach RGF/GLV Signaling Peptide pCTG134 Is Involved in a Regulatory Circuit That Sustains Auxin and Ethylene Actions

    Directory of Open Access Journals (Sweden)

    Nicola Busatto

    2017-10-01

    Full Text Available In vascular plants the cell-to-cell interactions coordinating morphogenetic and physiological processes are mediated, among others, by the action of hormones, among which also short mobile peptides were recognized to have roles as signals. Such peptide hormones (PHs are involved in defense responses, shoot and root growth, meristem homeostasis, organ abscission, nutrient signaling, hormone crosstalk and other developmental processes and act as both short and long distant ligands. In this work, the function of CTG134, a peach gene encoding a ROOT GROWTH FACTOR/GOLVEN-like PH expressed in mesocarp at the onset of ripening, was investigated for its role in mediating an auxin-ethylene crosstalk. In peach fruit, where an auxin-ethylene crosstalk mechanism is necessary to support climacteric ethylene synthesis, CTG134 expression peaked before that of ACS1 and was induced by auxin and 1-methylcyclopropene (1-MCP treatments, whereas it was minimally affected by ethylene. In addition, the promoter of CTG134 fused with the GUS reporter highlighted activity in plant parts in which the auxin-ethylene interplay is known to occur. Arabidopsis and tobacco plants overexpressing CTG134 showed abnormal root hair growth, similar to wild-type plants treated with a synthetic form of the sulfated peptide. Moreover, in tobacco, lateral root emergence and capsule size were also affected. In Arabidopsis overexpressing lines, molecular surveys demonstrated an impaired hormonal crosstalk, resulting in a re-modulated expression of a set of genes involved in both ethylene and auxin synthesis, transport and perception. These data support the role of pCTG134 as a mediator in an auxin-ethylene regulatory circuit and open the possibility to exploit this class of ligands for the rational design of new and environmental friendly agrochemicals able to cope with a rapidly changing environment.

  17. Sustainable Disruptions

    DEFF Research Database (Denmark)

    Friis, Silje Alberthe Kamille; Kjær, Lykke Bloch

    2016-01-01

    Since 2012 the Sustainable Disruptions (SD) project at the Laboratory for Sustainability at Design School Kolding (DK) has developed and tested a set of design thinking tools, specifically targeting the barriers to economically, socially, and environmentally sustainable business development....... The tools have been applied in practice in collaboration with 11 small and medium sized companies (SMEs). The study investigates these approaches to further understand how design thinking can contribute to sustainable transition in a business context. The study and the findings are relevant to organizations...... invested in the issue of sustainable business development, in particular the leaders and employees of SMEs, but also to design education seeking new ways to consciously handle and teach the complexity inherent in sustainable transformation. Findings indicate that the SD design thinking approach contributes...

  18. Successful reduction of high-sustained anti-idursulfase antibody titers by immune modulation therapy in a patient with severe mucopolysaccharidosis type II

    Directory of Open Access Journals (Sweden)

    Katherine H. Kim

    2015-03-01

    Full Text Available We report on a 6 year old boy with severe MPS II undergoing immune modulation therapy due to high IgG antibody titers to IV idursulfase and no significant decline in urinary GAG levels since initiating enzyme replacement therapy. He has complete deficiency of iduronate-2-sulfatase activity due to a submicroscopic deletion of the X chromosome involving the entire I2S gene but not including in the fragile X locus. At 19 months of age, IV idursulfase therapy at the recommended dose of 0.5 mg/kg/week was initiated and then increased to 1.0 mg/kg/week after no observed clinical improvement and no decline in urine GAG level. After one year of ERT at the increased dose, he had no significant decline in urinary GAG excretion and increase of anti-idursulfase IgG antibody titers to 102,000 with complete neutralizing antibodies. In light of the evidence of lack of efficacy of idursulfase therapy, the patient was started on an immune modulation regimen consisting of ofatumumab, bortezomib, methotrexate and IVIG for a 12 week period. Only a slight decrease in IgG titers and urine GAG levels was observed, leading to increased intensity of bortezomib administration and addition of dexamethasone to the regimen, while continuing with the current schedule ofatumumab, IVIG and methotrexate. Over 18 month period of immune modulation therapy, we observed a significant reduction in anti-idursulfase IgG titers and a moderate reduction in urine GAG levels compared to baseline. Modest clinical improvements were observed. Our experience suggests that future MPS II patients with a complete gene deletion may be likely to develop persistent anti-idursulfase antibody titers and may benefit from immune modulation therapy prior to the development of high titer levels.

  19. Computational sustainability

    CERN Document Server

    Kersting, Kristian; Morik, Katharina

    2016-01-01

    The book at hand gives an overview of the state of the art research in Computational Sustainability as well as case studies of different application scenarios. This covers topics such as renewable energy supply, energy storage and e-mobility, efficiency in data centers and networks, sustainable food and water supply, sustainable health, industrial production and quality, etc. The book describes computational methods and possible application scenarios.

  20. Angiotensin II induces reorganization of the actin cytoskeleton and myosin light-chain phosphorylation in podocytes through rho/ROCK-signaling pathway

    NARCIS (Netherlands)

    Wang, Siyuan; Chen, Cheng; Su, Ke; Zha, Dongqing; Liang, Wei; Hillebrands, J L; van Goor, Harry; Ding, Guohua

    2016-01-01

    Aims In the present study, we have evaluated the effect of angiotensin II (Ang II) on actin cytoskeleton reorganization and myosin light-chain (MLC) phosphorylation in podocytes to demonstrate whether the Rho/Rho-associated coiled kinase (ROCK) pathway is involved podocyte injury. Methods Eighteen

  1. Environmental enrichment improves learning and memory and long-term potentiation in young adult rats through a mechanism requiring mGluR5 signaling and sustained activation of p70s6k.

    Science.gov (United States)

    Hullinger, Rikki; O'Riordan, Kenneth; Burger, Corinna

    2015-11-01

    Previous studies from our lab have demonstrated that mild cognitive impairments identified early in life are predictive of cognitive deficits that develop with age, suggesting that enhancements in cognition at an early age can provide a buffer against age-related cognitive decline. Environmental enrichment has been shown to improve learning and memory in the rodent, but the impact of enrichment on synaptic plasticity and the molecular mechanisms behind enrichment are not completely understood. To address these unresolved issues, we have housed 2-month old rats in environmentally enriched (EE), socially enriched (SE), or standard housing (SC) and conducted tests of learning and memory formation at various time intervals. Here we demonstrate that animals that have been exposed to one month of social or environmental enrichment demonstrate enhanced learning and memory relative to standard housed controls. However, we have found that after 4months EE animals perform better than both SE and SC groups and demonstrate an enhanced hippocampal LTP. Our results demonstrate that this LTP is dependent on mGluR5 signaling, activation of ERK and mTOR signaling cascades, and sustained phosphorylation of p70s6 kinase, thus providing a potential target mechanism for future studies of cognitive enhancement in the rodent. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuilt...... theoretical lenses. It is proposed that three parameters concerning the ꞌtransformabilityꞌ of the building can contribute to a more nuanced understanding of sustainable transformation: technical aspects, programmatic requirements and narrative value. It is proposed that the concept of ꞌsustainable...

  3. AP2/ERF Transcription Factor, Ii049, Positively Regulates Lignan Biosynthesis in Isatis indigotica through Activating Salicylic Acid Signaling and Lignan/Lignin Pathway Genes.

    Science.gov (United States)

    Ma, Ruifang; Xiao, Ying; Lv, Zongyou; Tan, Hexin; Chen, Ruibing; Li, Qing; Chen, Junfeng; Wang, Yun; Yin, Jun; Zhang, Lei; Chen, Wansheng

    2017-01-01

    Lignans, such as lariciresinol and its derivatives, have been identified as effective antiviral ingredients in Isatis indigotica. Evidence suggests that the APETALA2/ethylene response factor (AP2/ERF) family might be related to the biosynthesis of lignans in I. indigotica. However, the special role played by the AP2/ERF family in the metabolism and its underlying putative mechanism still need to be elucidated. One novel AP2/ERF gene, named Ii049, was isolated and characterized from I. indigotica in this study. The quantitative real-time PCR analysis revealed that Ii049 was expressed highest in the root and responded to methyl jasmonate, salicylic acid (SA) and abscisic acid treatments to various degrees. Subcellular localization analysis indicated that Ii049 protein was localized in the nucleus. Knocking-down the expression of Ii049 caused a remarkable reduction of lignan/lignin contents and transcript levels of genes involved in the lignan/lignin biosynthetic pathway. Ii049 bound to the coupled element 1, RAV1AAT and CRTAREHVCBF2 motifs of genes IiPAL and IiCCR, the key structural genes in the lignan/lignin pathway. Furthermore, Ii049 was also essential for SA biosynthesis, and SA induced lignan accumulation in I. indigotica. Notably, the transgenic I. indigotica hairy roots overexpressing Ii049 showed high expression levels of lignan/lignin biosynthetic genes and SA content, resulting in significant accumulation of lignan/lignin. The best-engineered line (OVX049-10) produced 425.60 μg·g(-1) lariciresinol, an 8.3-fold increase compared with the wild type production. This study revealed the function of Ii049 in regulating lignan/lignin biosynthesis, which had the potential to increase the content of valuable lignan/lignin in economically significant medicinal plants.

  4. AP2/ERF Transcription Factor, Ii049, Positively Regulates Lignan Biosynthesis in Isatis indigotica through Activating Salicylic Acid Signaling and Lignan/Lignin Pathway Genes

    Directory of Open Access Journals (Sweden)

    Ruifang Ma

    2017-08-01

    Full Text Available Lignans, such as lariciresinol and its derivatives, have been identified as effective antiviral ingredients in Isatis indigotica. Evidence suggests that the APETALA2/ethylene response factor (AP2/ERF family might be related to the biosynthesis of lignans in I. indigotica. However, the special role played by the AP2/ERF family in the metabolism and its underlying putative mechanism still need to be elucidated. One novel AP2/ERF gene, named Ii049, was isolated and characterized from I. indigotica in this study. The quantitative real-time PCR analysis revealed that Ii049 was expressed highest in the root and responded to methyl jasmonate, salicylic acid (SA and abscisic acid treatments to various degrees. Subcellular localization analysis indicated that Ii049 protein was localized in the nucleus. Knocking-down the expression of Ii049 caused a remarkable reduction of lignan/lignin contents and transcript levels of genes involved in the lignan/lignin biosynthetic pathway. Ii049 bound to the coupled element 1, RAV1AAT and CRTAREHVCBF2 motifs of genes IiPAL and IiCCR, the key structural genes in the lignan/lignin pathway. Furthermore, Ii049 was also essential for SA biosynthesis, and SA induced lignan accumulation in I. indigotica. Notably, the transgenic I. indigotica hairy roots overexpressing Ii049 showed high expression levels of lignan/lignin biosynthetic genes and SA content, resulting in significant accumulation of lignan/lignin. The best-engineered line (OVX049-10 produced 425.60 μg·g−1 lariciresinol, an 8.3-fold increase compared with the wild type production. This study revealed the function of Ii049 in regulating lignan/lignin biosynthesis, which had the potential to increase the content of valuable lignan/lignin in economically significant medicinal plants.

  5. Illuminating the Signals Job Seekers Receive from an Employer's Community Involvement and Environmental Sustainability Practices: Insights into Why Most Job Seekers Are Attracted, Others Are Indifferent, and a Few Are Repelled

    Science.gov (United States)

    Jones, David A.; Willness, Chelsea R.; Heller, Kristin W.

    2016-01-01

    Evidence shows that job seekers tend to be attracted to employers known for their corporate social responsibility (CSR), but relatively little is known about the underlying psychological processes. Moreover, the literature is silent about whether and why some job seekers are unaffected, or even repelled by, an employer's CSR. We conducted a substantive replication of recent empirical support for three signal-based mechanisms by adapting the experimental manipulation used in a prior study while employing an alternative approach to analyzing a distinctly different type of data. We also extended prior work by examining other possible explanatory mechanisms and exploring potentially negative reactions to CSR. Using signaling theory as an overarching framework, we assessed research questions and tested hypotheses grounded in theories of employee recruitment and the psychology of CSR, specifying how an employer's CSR practices send signals from which job seekers draw inferences about unknown working conditions, thereby affecting their attraction to the employer. Study participants (N = 108) reviewed the webpages of two hiring companies and responded to open-ended questions about each employer. We content-analyzed written responses pertaining to one employer's webpages in which we embedded an experimental manipulation of information about the employer's community involvement or its environmentally sustainable practices. The results supported hypotheses that corroborate prior evidence for the “perceived value fit” and “expected employee treatment” mechanisms, and provided some, but relatively limited, support for the “anticipated pride” mechanism. Assessment of research questions highlighted previously undiscovered signal-based mechanisms that might help explain job seekers' attraction to CSR (e.g., inferences about the employer's positive work environment and financial standing, and the nature of its employees). Results also showed that a few people were less

  6. Illuminating the Signals Job Seekers Receive from an Employer's Community Involvement and Environmental Sustainability Practices: Insights into Why Most Job Seekers Are Attracted, Others Are Indifferent, and a Few Are Repelled.

    Science.gov (United States)

    Jones, David A; Willness, Chelsea R; Heller, Kristin W

    2016-01-01

    Evidence shows that job seekers tend to be attracted to employers known for their corporate social responsibility (CSR), but relatively little is known about the underlying psychological processes. Moreover, the literature is silent about whether and why some job seekers are unaffected, or even repelled by, an employer's CSR. We conducted a substantive replication of recent empirical support for three signal-based mechanisms by adapting the experimental manipulation used in a prior study while employing an alternative approach to analyzing a distinctly different type of data. We also extended prior work by examining other possible explanatory mechanisms and exploring potentially negative reactions to CSR. Using signaling theory as an overarching framework, we assessed research questions and tested hypotheses grounded in theories of employee recruitment and the psychology of CSR, specifying how an employer's CSR practices send signals from which job seekers draw inferences about unknown working conditions, thereby affecting their attraction to the employer. Study participants (N = 108) reviewed the webpages of two hiring companies and responded to open-ended questions about each employer. We content-analyzed written responses pertaining to one employer's webpages in which we embedded an experimental manipulation of information about the employer's community involvement or its environmentally sustainable practices. The results supported hypotheses that corroborate prior evidence for the "perceived value fit" and "expected employee treatment" mechanisms, and provided some, but relatively limited, support for the "anticipated pride" mechanism. Assessment of research questions highlighted previously undiscovered signal-based mechanisms that might help explain job seekers' attraction to CSR (e.g., inferences about the employer's positive work environment and financial standing, and the nature of its employees). Results also showed that a few people were less attracted

  7. Epigallocatechin-3-Gallate Ameliorates Angiotensin II-Induced Oxidative Stress and Apoptosis in Human Umbilical Vein Endothelial Cells through the Activation of Nrf2/Caspase-3 Signaling.

    Science.gov (United States)

    Zhou, Xiuli; Liang, Liwen; Zhao, Yan; Zhang, Hong

    2017-01-01

    This study aimed to investigate whether epigallocatechin-3-gallate (EGCG) shows antioxidant activity against angiotensin II (Ang II)-induced human umbilical vein endothelial cell (HUVEC) apoptosis. The viability of HUVECs was revealed by MTT and LDH assay. The cell apoptosis was detected by FITC-PI assay. A fluorescent probe assay was used to measure the reactive oxygen species (ROS) generation in HUVECs. Mitochondrial permeability transition pore (MPTP) opening, mitochondrial membrane potential, and caspase-3, -4, -8, -9 activities were also measured. We found that Ang II treatment increased the generation of ROS, enhanced MPTP opening and cytochrome c release, activated caspase-3/9, and consequently induced HUVEC apoptosis. EGCG treatment-suppressed Ang II induces the oxidative stress of HUVECs and mitochondria-related cell apoptosis. We also showed that the antioxidant activity pathway, including cytochrome c release, MPTP opening, and caspase-3/9 activation, is a key endogenous defensive system in HUVECs, provoking Ang II exposure. Our study revealed that increased expression of Nrf2 by EGCG could partially repress Ang II-induced injury effects. All of our findings indicated that EGCG treatment provides a protective effect for Ang II-induced HUVEC apoptosis by decreasing oxidative stress and ameliorating mitochondrial injury. © 2017 S. Karger AG, Basel.

  8. Controllable synthesis and characterisation of palladium (II) anticancer complex-loaded colloidal gelatin nanoparticles as a novel sustained-release delivery system in cancer therapy.

    Science.gov (United States)

    Alasvand, Neda; Saeidifar, Maryam; Saboury, Ali Akbar; Mozafari, Masoud

    2017-08-01

    Over the past few years, there have been several attempts to deliver anticancer drugs into the body. It has been shown that compared to other available carriers, colloidal gelatin nanoparticles (CGNPs) have distinct properties due to their exceptional physico-chemical and biological characteristics. In this study, a novel water-soluble palladium (II) anticancer complex was first synthesised, and then loaded into CGNPs. The CGNPs were synthesised through a two-step desolvation method with an average particle size of 378 nm. After confirming the stability of the drug in the nanoparticles, the drug-loaded CGNPs were tested for in vitro cytotoxicity against human breast cancer cells. The results showed that the average drug encapsulating efficiency and drug loading of CGNPs were 64 and 10 ± 2.1% (w/w), respectively. There was a slight shift to higher values of cumulative release, when the samples were tested in lower pH values. In addition, the in vitro cytotoxicity test indicated that the number of growing cells significantly decreased after 48 h in the presence of different concentrations of drug. The results also demonstrated that the released drug could bind to DNA by a static mechanism at low concentrations (0.57 µM) on the basis of hydrophobic and hydrogen binding interactions.

  9. Sustainable Transportation

    DEFF Research Database (Denmark)

    Hall, Ralph P.; Gudmundsson, Henrik; Marsden, Greg

    2014-01-01

    that relate to the construction and maintenance of transportation infrastructure and the operation or use of the different transportation modes. The concept of sustainable transportation emerged in response to these concerns as part of the broader notion of sustainable development. Given the transportation...

  10. Sustaining dairy

    NARCIS (Netherlands)

    Villarreal Herrera, Georgina

    2017-01-01

    Dairy in Europe has undergone many changes in the last few years—the abolition of milk production quotas being a fundamental one. This study explores these changes in relation to the sustained social and environmental viability of the sector and how dairy processors' sustainability

  11. Sustainable Universities

    DEFF Research Database (Denmark)

    Grindsted, Thomas Skou

    2011-01-01

    . Declarations tend to have impact on three trends. Firstly, there is emerging international consensus on the university’s role and function in relation to sustainable development; secondly, the emergence of national legislation, and thirdly, an emerging international competition to be leader in sustainable...... campus performance....

  12. Sustainable Transition

    DEFF Research Database (Denmark)

    Hansen, Ole Erik; Søndergård, Bent

    2014-01-01

    of agendas/vision, technologies, actors and institutions in the emergent design of an urban mobility system based on an electric car sharing system. Why. Designing for sustainability is a fundamental challenge for future design practices; designers have to obtain an ability to contribute to sustainable...

  13. Sustainable Learning

    Science.gov (United States)

    Cadwell, Louise; Dillon, Robert

    2011-01-01

    Green schools have moved into a new era that focuses on building a culture of sustainability in every aspect of learning in schools. In the early stages of sustainability education, the focus was on recycling and turning off the lights. Now, students and adults together are moving into the areas of advocacy and action that are based on a deep…

  14. Traditional and Modern Biomedical Prospecting: Part II-the Benefits: Approaches for a Sustainable Exploitation of Biodiversity (Secondary Metabolites and Biomaterials from Sponges).

    Science.gov (United States)

    Müller, Werner E G; Schröder, Heinz C; Wiens, Matthias; Perović-Ottstadt, Sanja; Batel, Renato; Müller, Isabel M

    2004-09-01

    applied in biomedicine. These compounds and biomaterials have been isolated/studied by members of the German Center of Excellence BIOTECmarin. The goal for the future is to successfully introduce some of these compounds in the treatment of human diseases in order to raise the public awareness on the richness and diversity of natural products, which should be sustainably exploited for human benefit.

  15. Sustainable consumption

    DEFF Research Database (Denmark)

    Prothero, Andrea; Dobscha, Susan; Freund, Jim

    2011-01-01

    This essay explores sustainable consumption and considers possible roles for marketing and consumer researchers and public policy makers in addressing the many sustainability challenges that pervade our planet. Future research approaches to this interdisciplinary topic need to be comprehensive...... and systematic and will benefit from a variety of different perspectives. There are a number of opportunities for future research, and three areas are explored in detail. First, the essay considers the inconsistency between the attitudes and behaviors of consumers with respect to sustainability; next, the agenda...... is broadened to explore the role of individual citizens in society; and finally, a macro institutional approach to fostering sustainability is explored. Each of these areas is examined in detail and possible research avenues and public policy initiatives are considered within each of these separate...

  16. Stabilizing Sustainability

    DEFF Research Database (Denmark)

    Reitan Andersen, Kirsti

    The publication of the Brundtland Report in 1987 put the topic of sustainable development on the political and corporate agenda. Defining sustainable development as “a development that meets the needs of the future without compromising the ability of future generations to meet their own needs......” (WCED, 1987, p. 43), the Report also put a positive spin on the issue of sustainability by upholding capitalist beliefs in the possibility of infinite growth in a world of finite resources. While growth has delivered benefits, however, it has done so unequally and unsustainably. This thesis focuses...... on the textile and fashion industry, one of the world’s most polluting industries and an industry to some degree notorious for leading the ‘race to the bottom’ in global labour standards. Despite being faced with increasing demands to practise sustainability, most textile and fashion companies continue to fail...

  17. Sustainability reporting

    NARCIS (Netherlands)

    Kolk, A.

    2005-01-01

    This article gives an overview of developments in sustainability (also sometimes labelled corporate social responsibility) reporting. The article will first briefly indicate how accountability on social and environmental issues started, already in the 1970s when social reports were published.

  18. Sustainable Cities

    DEFF Research Database (Denmark)

    Georg, Susse; Garza de Linde, Gabriela Lucía

    Judging from the number of communities and cities striving or claiming to be sustainable and how often eco-development is invoked as the means for urban regeneration, it appears that sustainable and eco-development have become “the leading paradigm within urban development” (Whitehead 2003......), urban design competitions are understudied mechanisms for bringing about field level changes. Drawing on actor network theory, this paper examines how urban design competitions may bring about changes within the professional field through the use of intermediaries such as a sustainable planning....../assessment tool. The context for our study is urban regeneration in one Danish city, which had been suffering from industrial decline and which is currently investing in establishing a “sustainable city”. Based on this case study we explore how the insights and inspiration evoked in working with the tool...

  19. Sustainable responsibilities?

    DEFF Research Database (Denmark)

    Lystbæk, Christian Tang

    2015-01-01

    This working paper analyzes the conceptions of corporate responsibility for sustainable development in EU policies on CSR. The notion of corporate responsibility has until recently been limited to economical and legal responsibilities. Based on this narrow conception of corporate responsibility.......e. a combination of destruction and construction, this chapter will deconstruct conceptions of responsibility for sustainable development in these EU documents on CSR. A deconstructive conceptual analysis involves destructing dominant interpretations of a text and allowing for constructions of alternative...... such as sustainability actually means, but on what the concept says and does not say. A deconstructive analysis of EU policies on CSR, then, pinpoints that such policies are sites of conceptual struggles. This kind of analysis is suitable for studying conceptions of corporate responsibility for sustainable development...

  20. Agriculture: Sustainability

    Science.gov (United States)

    Sustainability creates and maintains the conditions under which humans and nature can exist in productive harmony, that permit fulfilling the food, feed, and fiber needs of our country and the social, economic and other requirements.

  1. Sustainable finance

    OpenAIRE

    Boersma-de Jong, Margreet F.

    2012-01-01

    Presentation for Springschool of Strategy, University of Groningen, 10 October 2012. The role of CSR is to stimulate ethical behaviour, and as a result, mutual trust in society. Advantage of CSR for the company and the evolution of CSR. From CSR to Sustainable Finance: how does CSR influence Sustainable Business Administration & Management Accounting, Financial Leadership and what is the importance of CSR in the financial sector

  2. SUSTAINABLE TRANSPORTATION

    Directory of Open Access Journals (Sweden)

    Linda STEG

    2007-01-01

    Full Text Available This paper discusses possible contributions of psychologists to sustainable transportation. It is argued that in order to reach sustainable transportation, among others, behaviour changes of individual car users are needed. As transport policies will be more effective if they target important antecedents of travel behaviour, first, factors influencing such behaviour are discussed. It is argued that car use is very attractive and sometimes even necessary for many different reasons. This implies that a combination of policies is called for, each targeting different factors that support car use and hinder the use of more sustainable modes of transport. Next, the paper elaborates on policy strategies that may be employed to achieve sustainable transportation by changing car use. Increasing the attractiveness of sustainable transport modes by means of pull measures seems not sufficient to reduce the level of car use. Besides, car use should be made less attractive by means of push measures to force drivers to reconsider their travel behaviour. The acceptability of such policies may be increased by clearly communicating the aim of these policies, and the expected positive consequences (e.g., less congestion, improved environmental quality. Moreover, possible negative effects for individual freedom may be compensated by implementing additional policies aimed at facilitating the use of sustainable transport modes.

  3. Sustainable markets for sustainable energy

    Energy Technology Data Exchange (ETDEWEB)

    Millan, J.; Smyser, C.

    1997-12-01

    The author discusses how the Inter-American Development Bank (IDB) is involved in sustainable energy development. It presently has 50 loans and grants for non conventional renewable energy projects and ten grants for efficiency programs for $600 and $17 million respectively, representing 100 MW of power. The IDB is concerned with how to create a sustainable market for sustainable energy projects. The IDB is trying to work with government, private sector, NGOs, trading allies, credit sources, and regulators to find proper roles for such projects. He discusses how the IDB is working to expand its vision and objectives in renewable energy projects in Central and South America.

  4. Angiotensin II Type 1 receptor (AT1) signaling in astrocytes regulates synaptic degeneration-induced leukocyte entry to the central nervous system

    DEFF Research Database (Denmark)

    Füchtbauer, L; Groth-Rasmussen, Maria; Holm, Thomas Hellesøe

    2011-01-01

    in the dentate gyrus following axonal transection was totally abrogated in GFAP-IκBα-dn mice. Whereas angiotensin II was upregulated in microglia and astrocytes in the dentate gyrus post-lesion, AT1 was exclusively expressed on astrocytes. Blocking AT1 with Candesartan led to significant increase in numbers...

  5. Prony-Householder method applied to 31P NMR signals: II. Study of conjugates of ara-AMP with lactosaminated albumin.

    Science.gov (United States)

    Polichetti, A; Viti, V; Barone, P; Colonna, F; Fiume, L

    1992-12-01

    Conjugates of 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) with lactosaminated albumin (L-SA), obtained by using two different coupling procedures, produce antibodies in rats and mice which display only a small cross-reactivity. 31P NMR signals from the two conjugates have been examined to clarify whether different lysine and histidine residues are involved in the two reaction pathways. The occurrence of different chemical shifts and linewidths between the two conjugates, as evidenced by processing the signals with the Prony-Householder method, indicates the formation of two different complexes.

  6. Roundtabling Sustainability

    DEFF Research Database (Denmark)

    Ponte, Stefano

    2014-01-01

    The willingness of public authority to delegate social and environmental regulation to the private sector has varied from sector to sector, but has often led to the establishment of ‘voluntary’ standards and certifications on sustainability. Many of these have taken the form of ‘stewardship...... councils’ and ‘sustainability roundtables’ and have been designed around a set of institutional features seeking to establish legitimacy, fend off possible criticism, and ‘sell’ certifications to potential users. The concept of ‘roundtabling’ emphasizes the fitting a variety of commodity......-specific sustainability situations into a form that not only ‘hears more voices’ (as in ‘multi-stakeholder’), but also portrays to give them equal standing at the table of negotiations (roundtable), thus raising higher expectations on accountability, transparency and inclusiveness. In this article, I examine to what...

  7. Estimation of Potential Interference Immunity of Radio Reception with Spatial Signal Processing in Mutipath Radio-Communication Channels. Part II. Meter and Decimeter Ranges

    Science.gov (United States)

    Lvov, A. V.; Metelev, S. L.

    2016-11-01

    We propose simulation models for estimating the interference immunity of radio reception using the spatial processing of signals in the airborne and ground-based communication channels of the meter and decimeter wavelength ranges. The ultimate achievable interference immunity under various radio-wave propagation conditions is studied.

  8. Sustainability Evaluation.

    Science.gov (United States)

    Stichnothe, Heinz

    2017-03-17

    The long-term substitution of fossil resources can only be achieved through a bio-based economy, with biorefineries and bio-based products playing a major role. However, it is important to assess the implications of the transition to a bio-based economy. Life cycle-based sustainability assessment is probably the most suitable approach to quantify impacts and to identify trade-offs at multiple levels. The extended utilisation of biomass can cause land use change and affect food security of the most vulnerable people throughout the world. Although this is mainly a political issue and governments should be responsible, the responsibility is shifted to companies producing biofuels and other bio-based products. Organic wastes and lignocellulosic biomass are considered to be the preferred feedstock for the production of bio-based products. However, it is unlikely that a bio-based economy can rely only on organic wastes and lignocellulosic biomass.It is crucial to identify potential problems related to socio-economic and environmental issues. Currently there are many approaches to the sustainability of bio-based products, both quantitative and qualitative. However, results of different calculation methods are not necessarily comparable and can cause confusion among decision-makers, stakeholders and the public.Hence, a harmonised, globally agreed approach would be the best solution to secure sustainable biomass/biofuels/bio-based chemicals production and trade, and to avoid indirect effects (e.g. indirect land use change). However, there is still a long way to go.Generally, the selection of suitable indicators that serve the purpose of sustainability assessment is very context-specific. Therefore, it is recommended to use a flexible and modular approach that can be adapted to various purposes. A conceptual model for the selection of sustainability indicators is provided that facilitates identifying suitable sustainability indicators based on relevance and significance in a

  9. p21(CIP1/WAF1)-dependent inhibition of cardiac hypertrophy in response to Angiotensin II involves Akt/Myc and pRb signaling.

    Science.gov (United States)

    Hauck, Ludger; Grothe, Daniela; Billia, Filio

    2016-09-01

    The cyclin-dependent kinase inhibitor p21(CIP1/WAF1) (p21) is highly expressed in the adult heart. However, in response to stress, its expression is downregulated. Therefore, we investigated the role of p21 in the regulation of cardiac hypertrophic growth. At 2 months of age, p21 knockout mice (p21KO) lack an overt cardiac phenotype. In contrast, by 10 months of age, p21KO developed age-dependent cardiac hypertrophy and heart failure. After 3 weeks of trans-aortic banding (TAB), the heart/body weight ratio in 11 week old p21KO mice increased by 57%, as compared to 42% in wild type mice indicating that p21KO have a higher susceptibility to pressure overload-induced cardiac hypertrophy. We then chronically infused 8 week old wild type mice with Angiotensin II (2.0mg/kg/min) or saline subcutaneously by osmotic pumps for 14 days. Recombinant TAT conjugated p21 protein variants (10mg/kg body weight) or saline were intraperitoneally injected once daily for 14 days into Angiotensin II and saline-infused animals. Angiotensin II treated mice developed pathological cardiac hypertrophy with an average increase of 38% in heart/body weight ratios, as compared to saline-treated controls. Reconstitution of p21 function by TAT.p21 protein transduction prevented Angiotensin II-dependent development of cardiac hypertrophy and failure. Taken together, our genetic and biochemical data show an important function of p21 in the regulation of growth-related processes in the heart. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Rapid metabolism of exogenous angiotensin II by catecholaminergic neuronal cells in culture media.

    Science.gov (United States)

    Basu, Urmi; Seravalli, Javier; Madayiputhiya, Nandakumar; Adamec, Jiri; Case, Adam J; Zimmerman, Matthew C

    2015-02-01

    Angiotensin II (AngII) acts on central neurons to increase neuronal firing and induce sympathoexcitation, which contribute to the pathogenesis of cardiovascular diseases including hypertension and heart failure. Numerous studies have examined the precise AngII-induced intraneuronal signaling mechanism in an attempt to identify new therapeutic targets for these diseases. Considering the technical challenges in studying specific intraneuronal signaling pathways in vivo, especially in the cardiovascular control brain regions, most studies have relied on neuronal cell culture models. However, there are numerous limitations in using cell culture models to study AngII intraneuronal signaling, including the lack of evidence indicating the stability of AngII in culture media. Herein, we tested the hypothesis that exogenous AngII is rapidly metabolized in neuronal cell culture media. Using liquid chromatography-tandem mass spectrometry, we measured levels of AngII and its metabolites, Ang III, Ang IV, and Ang-1-7, in neuronal cell culture media after administration of exogenous AngII (100 nmol/L) to a neuronal cell culture model (CATH.a neurons). AngII levels rapidly declined in the media, returning to near baseline levels within 3 h of administration. Additionally, levels of Ang III and Ang-1-7 acutely increased, while levels of Ang IV remained unchanged. Replenishing the media with exogenous AngII every 3 h for 24 h resulted in a consistent and significant increase in AngII levels for the duration of the treatment period. These data indicate that AngII is rapidly metabolized in neuronal cell culture media, and replenishing the media at least every 3 h is needed to sustain chronically elevated levels. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  11. Sustainable Soesterkwartier

    NARCIS (Netherlands)

    Abrahams, H.; Goosen, H.; Jong, de F.; Sickmann, J.; Prins, D.

    2010-01-01

    The municipality of Amersfoort wants to construct an endurable and sustainable eco-town in the Soesterkwartier neighbourhood, by taking future climate change into account. The impact of climate change at the location of the proposed eco-town was studied by a literature review.

  12. Sustainable agriculture

    International Development Research Centre (IDRC) Digital Library (Canada)

    New farming techniques, better food security. Since 1970, IDRC-supported research has introduced sustainable agricultural practices to farmers and communities across the devel- oping world. The result: higher productivity, less poverty, greater food security, and a healthier environment. Opportunities grow on trees in ...

  13. Sustainable Development

    African Journals Online (AJOL)

    Tsegai Berhane Ghebretekle

    Abstract. This article examines the concept of sustainable development after the Post-. 2015 Paris Climate Change Agreement with particular emphasis on Ethiopia. Various African countries are vulnerable to climate change, as is evidenced by recent droughts. Ethiopia is selected as a case study in light of its pace in.

  14. Sustainable machining

    CERN Document Server

    2017-01-01

    This book provides an overview on current sustainable machining. Its chapters cover the concept in economic, social and environmental dimensions. It provides the reader with proper ways to handle several pollutants produced during the machining process. The book is useful on both undergraduate and postgraduate levels and it is of interest to all those working with manufacturing and machining technology.

  15. Architecture Sustainability

    NARCIS (Netherlands)

    Avgeriou, Paris; Stal, Michael; Hilliard, Rich

    2013-01-01

    Software architecture is the foundation of software system development, encompassing a system's architects' and stakeholders' strategic decisions. A special issue of IEEE Software is intended to raise awareness of architecture sustainability issues and increase interest and work in the area. The

  16. Sustainability reporting

    NARCIS (Netherlands)

    Kolk, A.

    2005-01-01

    This article gives an overview of developments in sustainability (also sometimes labelled corporate social responsibility) reporting. It The article will first briefly indicate how accountability on social and environmental issues started, already in the 1970s when social reports were published.

  17. Exergy sustainability.

    Energy Technology Data Exchange (ETDEWEB)

    Robinett, Rush D. III (.; ); Wilson, David Gerald; Reed, Alfred W.

    2006-05-01

    Exergy is the elixir of life. Exergy is that portion of energy available to do work. Elixir is defined as a substance held capable of prolonging life indefinitely, which implies sustainability of life. In terms of mathematics and engineering, exergy sustainability is defined as the continuous compensation of irreversible entropy production in an open system with an impedance and capacity-matched persistent exergy source. Irreversible and nonequilibrium thermodynamic concepts are combined with self-organizing systems theories as well as nonlinear control and stability analyses to explain this definition. In particular, this paper provides a missing link in the analysis of self-organizing systems: a tie between irreversible thermodynamics and Hamiltonian systems. As a result of this work, the concept of ''on the edge of chaos'' is formulated as a set of necessary and sufficient conditions for stability and performance of sustainable systems. This interplay between exergy rate and irreversible entropy production rate can be described as Yin and Yang control: the dialectic synthesis of opposing power flows. In addition, exergy is shown to be a fundamental driver and necessary input for sustainable systems, since exergy input in the form of power is a single point of failure for self-organizing, adaptable systems.

  18. Sustainable processing

    DEFF Research Database (Denmark)

    Kristensen, Niels Heine

    2004-01-01

    Kristensen_NH and_Beck A: Sustainable processing. In Otto Schmid, Alexander Beck and Ursula Kretzschmar (Editors) (2004): Underlying Principles in Organic and "Low-Input Food" Processing - Literature Survey. Research Institute of Organic Agriculture FiBL, CH-5070 Frick, Switzerland. ISBN 3-906081-58-3...

  19. Sustainable finance

    NARCIS (Netherlands)

    dr. Margreet F. Boersma-de Jong

    2012-01-01

    Presentation for Springschool of Strategy, University of Groningen, 10 October 2012. The role of CSR is to stimulate ethical behaviour, and as a result, mutual trust in society. Advantage of CSR for the company and the evolution of CSR. From CSR to Sustainable Finance: how does CSR influence

  20. Effects of exposure to DAMPS and GSM signals on ornithine decarboxylase (ODC) activity: II. SH-SY5Y human neuroblastoma cells.

    Science.gov (United States)

    Billaudel, Bernard; Taxile, Murielle; Poulletier de Gannes, Florence; Ruffie, Gilles; Lagroye, Isabelle; Veyret, Bernard

    2009-06-01

    An increase in Ornithine Decarboxylase (ODC) activity was reported in L929 murine fibroblast cells after exposure to a digital cellular telephone signal. This result was not confirmed by several other studies, including the one reported in a companion paper. As a partner in the Perform-B programme, we extended this study to human neuroblastoma cells (SH-SY5Y), using well-defined waveguide systems to imitate exposure to radiofrequency radiation (RFR): Digital Advanced Mobile Phone System (DAMPS) or Global System for Mobile communications (GSM) signals emitted by mobile phones. Human neuroblastoma cells (SH-SY5Y) were exposed at various Specific Absorption Rates (SAR) to DAMPS or GSM signals using different set-ups. Cell ODC activities were assayed using 14CO2 generation from 14C-labeled L-ornithine. SH-SY5Y cells were incubated for 20 hours, and were blindly exposed to 50 Hz-modulated DAMPS-835 or 217 Hz-modulated GSM-1800 for 8 or 24 h using Information Technologies in Society (IT'IS) waveguides equipped with fans. After cell lysis, ODC activity was determined using 14C-labeled L-ornithine. ODC activity was estimated by the 14CO2 generated from 14C-labeled L-ornithine, as generated d.p.m. 14CO2/h/mg protein. The results showed that, irrespective of the signal used (835 MHz/DAMPS, or 1800 MHz/GSM) and exposure conditions (duration and SAR), human SH-SY5Y neuroblastoma cells did not exhibit any alteration in ODC enzyme activity. This work did not show a significant effect of mobile phone RFR exposure on ODC activity in neuroblastoma cells (SH-SY5Y).

  1. Highly active microbial phosphoantigen induces rapid yet sustained MEK/Erk- and PI-3K/Akt-mediated signal transduction in anti-tumor human gammadelta T-cells.

    Directory of Open Access Journals (Sweden)

    Daniel V Correia

    Full Text Available BACKGROUND: The unique responsiveness of Vgamma9Vdelta2 T-cells, the major gammadelta subset of human peripheral blood, to non-peptidic prenyl pyrophosphate antigens constitutes the basis of current gammadelta T-cell-based cancer immunotherapy strategies. However, the molecular mechanisms responsible for phosphoantigen-mediated activation of human gammadelta T-cells remain unclear. In particular, previous reports have described a very slow kinetics of activation of T-cell receptor (TCR-associated signal transduction pathways by isopentenyl pyrophosphate and bromohydrin pyrophosphate, seemingly incompatible with direct binding of these antigens to the Vgamma9Vdelta2 TCR. Here we have studied the most potent natural phosphoantigen yet identified, (E-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP, produced by Eubacteria and Protozoa, and examined its gammadelta T-cell activation and anti-tumor properties. METHODOLOGY/PRINCIPAL FINDINGS: We have performed a comparative study between HMB-PP and the anti-CD3epsilon monoclonal antibody OKT3, used as a reference inducer of bona fide TCR signaling, and followed multiple cellular and molecular gammadelta T-cell activation events. We show that HMB-PP activates MEK/Erk and PI-3K/Akt pathways as rapidly as OKT3, and induces an almost identical transcriptional profile in Vgamma9(+ T-cells. Moreover, MEK/Erk and PI-3K/Akt activities are indispensable for the cellular effects of HMB-PP, including gammadelta T-cell activation, proliferation and anti-tumor cytotoxicity, which are also abolished upon antibody blockade of the Vgamma9(+ TCR Surprisingly, HMB-PP treatment does not induce down-modulation of surface TCR levels, and thereby sustains gammadelta T-cell activation upon re-stimulation. This ultimately translates in potent human gammadelta T-cell anti-tumor function both in vitro and in vivo upon transplantation of human leukemia cells into lymphopenic mice, CONCLUSIONS/SIGNIFICANCE: The development of

  2. Cardiac lineage protein-1 (CLP-1) regulates cardiac remodeling via transcriptional modulation of diverse hypertrophic and fibrotic responses and angiotensin II-transforming growth factor β (TGF-β1) signaling axis.

    Science.gov (United States)

    Mascareno, Eduardo; Galatioto, Josephine; Rozenberg, Inna; Salciccioli, Louis; Kamran, Haroon; Lazar, Jason M; Liu, Fang; Pedrazzini, Thierry; Siddiqui, M A Q

    2012-04-13

    It is well known that the renin-angiotensin system contributes to left ventricular hypertrophy and fibrosis, a major determinant of myocardial stiffness. TGF-β1 and renin-angiotensin system signaling alters the fibroblast phenotype by promoting its differentiation into morphologically distinct pathological myofibroblasts, which potentiates collagen synthesis and fibrosis and causes enhanced extracellular matrix deposition. However, the atrial natriuretic peptide, which is induced during left ventricular hypertrophy, plays an anti-fibrogenic and anti-hypertrophic role by blocking, among others, the TGF-β-induced nuclear localization of Smads. It is not clear how the hypertrophic and fibrotic responses are transcriptionally regulated. CLP-1, the mouse homolog of human hexamethylene bis-acetamide inducible-1 (HEXIM-1), regulates the pTEFb activity via direct association with pTEFb causing inhibition of the Cdk9-mediated serine 2 phosphorylation in the carboxyl-terminal domain of RNA polymerase II. It was recently reported that the serine kinase activity of Cdk9 not only targets RNA polymerase II but also the conserved serine residues of the polylinker region in Smad3, suggesting that CLP-1-mediated changes in pTEFb activity may trigger Cdk9-dependent Smad3 signaling that can modulate collagen expression and fibrosis. In this study, we evaluated the role of CLP-1 in vivo in induction of left ventricular hypertrophy in angiotensinogen-overexpressing transgenic mice harboring CLP-1 heterozygosity. We observed that introduction of CLP-1 haplodeficiency in the transgenic α-myosin heavy chain-angiotensinogen mice causes prominent changes in hypertrophic and fibrotic responses accompanied by augmentation of Smad3/Stat3 signaling. Together, our findings underscore the critical role of CLP-1 in remodeling of the genetic response during hypertrophy and fibrosis.

  3. Cardiac Lineage Protein-1 (CLP-1) Regulates Cardiac Remodeling via Transcriptional Modulation of Diverse Hypertrophic and Fibrotic Responses and Angiotensin II-transforming Growth Factor β (TGF-β1) Signaling Axis*

    Science.gov (United States)

    Mascareno, Eduardo; Galatioto, Josephine; Rozenberg, Inna; Salciccioli, Louis; Kamran, Haroon; Lazar, Jason M.; Liu, Fang; Pedrazzini, Thierry; Siddiqui, M. A. Q.

    2012-01-01

    It is well known that the renin-angiotensin system contributes to left ventricular hypertrophy and fibrosis, a major determinant of myocardial stiffness. TGF-β1 and renin-angiotensin system signaling alters the fibroblast phenotype by promoting its differentiation into morphologically distinct pathological myofibroblasts, which potentiates collagen synthesis and fibrosis and causes enhanced extracellular matrix deposition. However, the atrial natriuretic peptide, which is induced during left ventricular hypertrophy, plays an anti-fibrogenic and anti-hypertrophic role by blocking, among others, the TGF-β-induced nuclear localization of Smads. It is not clear how the hypertrophic and fibrotic responses are transcriptionally regulated. CLP-1, the mouse homolog of human hexamethylene bis-acetamide inducible-1 (HEXIM-1), regulates the pTEFb activity via direct association with pTEFb causing inhibition of the Cdk9-mediated serine 2 phosphorylation in the carboxyl-terminal domain of RNA polymerase II. It was recently reported that the serine kinase activity of Cdk9 not only targets RNA polymerase II but also the conserved serine residues of the polylinker region in Smad3, suggesting that CLP-1-mediated changes in pTEFb activity may trigger Cdk9-dependent Smad3 signaling that can modulate collagen expression and fibrosis. In this study, we evaluated the role of CLP-1 in vivo in induction of left ventricular hypertrophy in angiotensinogen-overexpressing transgenic mice harboring CLP-1 heterozygosity. We observed that introduction of CLP-1 haplodeficiency in the transgenic α-myosin heavy chain-angiotensinogen mice causes prominent changes in hypertrophic and fibrotic responses accompanied by augmentation of Smad3/Stat3 signaling. Together, our findings underscore the critical role of CLP-1 in remodeling of the genetic response during hypertrophy and fibrosis. PMID:22308025

  4. Analysis of the V2 Vasopressin Receptor (V2R) Mutations Causing Partial Nephrogenic Diabetes Insipidus Highlights a Sustainable Signaling by a Non-peptide V2R Agonist.

    Science.gov (United States)

    Makita, Noriko; Sato, Tomohiko; Yajima-Shoji, Yuki; Sato, Junichiro; Manaka, Katsunori; Eda-Hashimoto, Makiko; Ootaki, Masanori; Matsumoto, Naoki; Nangaku, Masaomi; Iiri, Taroh

    2016-10-21

    Disease-causing mutations in G protein-coupled receptor (GPCR) genes, including the V2 vasopressin receptor (V2R) gene, often cause misfolded receptors, leading to a defect in plasma membrane trafficking. A novel V2R mutation, T273M, identified in a boy with partial nephrogenic diabetes insipidus (NDI), shows intracellular localization and partial defects similar to the two mutants we described previously (10). Although non-peptide V2R antagonists have been shown to rescue the membrane localization of V2R mutants, their level of functional rescue is weak. Interestingly, it has been reported that a non-peptide agonist, OPC51803, activates misfolded V2R mutants intracellularly without degradation, thus potentially serving as a therapeutic agent against NDI (14). In our current experiments, however, a peptide antagonist blocked arginine vasopressin (AVP)- or OPC51803-stimulated cAMP accumulation both in COS-7 and MDCK cells, suggesting that OPC51803 mainly stimulates cell surface V2R mutants. In addition, our analyses revealed that OPC51803 works not only as a non-peptide agonist that causes activation/β-arrestin-dependent desensitization of V2R mutants expressed at the plasma membrane but also as a pharmacochaperone that promotes the endoplasmic reticulum-retained mutant maturation and trafficking to the plasma membrane. The ratio of the pharmacochaperone effect to the desensitization effect likely correlates negatively with the residual function of the tested mutants, suggesting that OPC5 has a more favorable effect on the V2R mutants with a less residual function. We speculated that the canceling of the desensitization effect of OPC51803 by the pharmacochaperone effect after long-term treatment may produce sustainable signaling, and thus pharmacochaperone agonists such as OPC51803 may serve as promising therapeutics for NDI caused by misfolded V2R mutants. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Thermal Resonance in Signal Transmission

    OpenAIRE

    Reigada Sanz, Ramon; Sarmiento, Antonio; Lindenberg, Katja

    2001-01-01

    We use temperature tuning to control signal propagation in simple one-dimensional arrays of masses connected by hard anharmonic springs and with no local potentials. In our numerical model a sustained signal is applied at one site of a chain immersed in a thermal environment and the signal-to-noise ratio is measured at each oscillator. We show that raising the temperature can lead to enhanced signal propagation along the chain, resulting in thermal resonance effects akin to the resonance obse...

  6. Blocking the QB-binding site of photosystem II by tenuazonic acid, a non-host-specific toxin of Alternaria alternata, activates singlet oxygen-mediated and EXECUTER-dependent signalling in Arabidopsis.

    Science.gov (United States)

    Chen, Shiguo; Kim, Chanhong; Lee, Je Min; Lee, Hyun-Ah; Fei, Zhangjun; Wang, Liangsheng; Apel, Klaus

    2015-06-01

    Necrotrophic fungal pathogens produce toxic compounds that induce cell death in infected plants. Often, the primary targets of these toxins and the way a plant responds to them are not known. In the present work, the effect of tenuazonic acid (TeA), a non-host-specific toxin of Alternaria alternata, on Arabidopsis thaliana has been analysed. TeA blocks the QB -binding site at the acceptor side of photosystem II (PSII). As a result, charge recombination at the reaction centre (RC) of PSII is expected to enhance the formation of the excited triplet state of the RC chlorophyll that promotes generation of singlet oxygen ((1)O₂). (1)O₂ activates a signalling pathway that depends on the two EXECUTER (EX) proteins EX1 and EX2 and triggers a programmed cell death response. In seedlings treated with TeA at half-inhibition concentration (1)O₂-mediated and EX-dependent signalling is activated as indicated by the rapid and transient up-regulation of (1)O₂-responsive genes in wild type, and its suppression in ex1/ex2 mutants. Lesion formation occurs when seedlings are exposed to higher concentrations of TeA for a longer period of time. Under these conditions, the programmed cell death response triggered by (1)O₂-mediated and EX-dependent signalling is superimposed by other events that also contribute to lesion formation. © 2014 John Wiley & Sons Ltd.

  7. Novel dinuclear platinum(II complexes targets NFkappaB signaling pathway to induce apoptosis and inhibit metabolism of MCF-7 breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Arkadiusz Surazyński

    2010-01-01

    Full Text Available Four novel dinuclear platinum(II complexes of formula [Pt2L4(berenil2]Cl4 (Pt1-Pt4 where L is piperazine (Pt1, 4-picoline (Pt2, 3-picoline (Pt3 or isopropylamine (Pt4 were compared to cisplatin in respect to collagen biosynthesis, beta1- integrin receptor, IGF-I receptor, phosphorylated MAP-kinases (ERK1/ERK2 and p38, phosphorylated Akt kinase expression and appearance of apoptosis in MCF-7 breast cancer cells. It was found that Pt1-Pt4 were more active inhibitor of collagen biosynthesis than cisplatin. The expression of IGF-I and beta1 integrin receptor, as well as phosphorylated MAPK, (ERK1 and ERK2 and p38 was significantly increased in cells incubated for 24 h with 20 muM Pt1-Pt4 compared to the control, not treated cells. The phenomenon was related to the increase expresion of NFkappaB by Pt1-Pt4 as shown by Western immunoblot analysis. Experiments made with annexin V-FITC and detection of apoptosis by a fluorescent microscopy assay revealed that novel dinuclear platinum(II complexes (Pt1-Pt4 inhibited the proliferation of MCF-7 breast cancer cells by increasing the number of apoptotic and necrotic cells.

  8. SUSTAINABLE CORPORATE AND SUSTAINABLE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    DORU CÎRNU

    2017-06-01

    Full Text Available In recent decades, the image of the international business environment has changed significantly. Studies conducted by UNCTAD shows that corporate phenomenon developments in the world economy is growing. Without claiming to present an exhaustive topic so vast we tried to capture some "facets" of sustainable development from the perspective of multinational corporations, given the expansion of these economic entities and strengthening their power in the global economy. We present more negative aspects of the actions of multinational corporations in terms of sustainable development, it is very important to know both sides of the coin, which will not only help transnational giants including release. Based on issues such as corporate social responsibility, environmental pollution and workers' rights, we sought to counter official statements. The conclusion is that these economic entities are real forces that can not be ignored in today's world and the obvious problem of sustainable development can not be addressed independently of the phenomenon, context we also identified some possible solutions to conflict of corporations and essence of the concept of sustainable development.

  9. Sustainable Consumption

    DEFF Research Database (Denmark)

    Røpke, Inge

    2015-01-01

    in wider social, economic and technological frameworks is emphasised. In particular, the chapter is inspired by practice theory and transition theory. First, various trends in consumption are outlined to highlight some of the challenges for sustainability transitions. Then, it is discussed how consumption...... patterns are shaped over time and what should be considered in sustainability strategies. While discussions on consumption often take their point of departure in the perspective of the individual and then zoom to the wider context, the present approach is the opposite. The outline starts with the basic...... biophysical, distributional and economic conditions for high consumption in rich countries and then zooms in on the coevolution of provision systems and consumption, and how consumption is shaped by practices and projects in everyday life. Furthermore, the paper discusses whether and how transition...

  10. Sustainable Buildings

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Elle, Morten

    The scientific community agrees that: all countries must drastically and rapidly reduce their CO2 emissions and that energy efficient houses play a decisive role in this. The general attitude at the workshop on Sustainable Buildings was that we face large and serious climate change problems that ...... that need urgent action. The built environment is an obvious area to put effort into because of the large and cost-effective energy saving potential and potential for Renewable Energy-based supply systems for buildings.......The scientific community agrees that: all countries must drastically and rapidly reduce their CO2 emissions and that energy efficient houses play a decisive role in this. The general attitude at the workshop on Sustainable Buildings was that we face large and serious climate change problems...

  11. Digital signal processing

    CERN Document Server

    O'Shea, Peter; Hussain, Zahir M

    2011-01-01

    In three parts, this book contributes to the advancement of engineering education and that serves as a general reference on digital signal processing. Part I presents the basics of analog and digital signals and systems in the time and frequency domain. It covers the core topics: convolution, transforms, filters, and random signal analysis. It also treats important applications including signal detection in noise, radar range estimation for airborne targets, binary communication systems, channel estimation, banking and financial applications, and audio effects production. Part II considers sel

  12. Study of the $H^0/A^0 \\to \\tau \\mu$ signal at the hadronic colliders and intercalibration of the D0 calorimeter at Tevatron Run II

    Energy Technology Data Exchange (ETDEWEB)

    Delsart, Pierre Antoine [Claude Bernard Univ. Lyon (France)

    2003-10-13

    This thesis was realized in collaboration with the "theory'' group and the "D0" group of IPNL. Within D0 we have worked on a component of the calibration of the detector's calorimeter : the intercalibration. Using the fact the physics is $\\phi$-symmetric in D0, we created and applied statistical methods for a relative calibration of the $\\phi$-symmetric parts of the calorimeter. Work on particle physics concerned the two Higgs doublet model. In such models leptonic number violation is possible : we have simulated the $H^0/A^0 \\to \\tau \\mu$ signal in order to study the discovery potential and the constraints on the coupling responsible for this decay.

  13. SUSTAINABLE CHEMISTRY FOR SUSTAINABLE INDUSTRY

    Directory of Open Access Journals (Sweden)

    G. Rizzuto

    2015-01-01

    Full Text Available Foundry Alfe Chem is an industrial reality working in the field of lubrication and chemical auxiliaries for industrial processes, which falls within the framework of the emerging and increasingly important «green chemistry». The goal of the company is to develop products that are more environmentally friendly by using raw materials from renewable sources; specifically, Foundry Alfe Chem has a program of self-sustainability that contemplates, for the foreseeable future, the direct production of renewable raw materials. The company has developed a new dedicated product line, Olitema, whose purpose is to offer highly technological solutions with complete environmental sustainability. In this context, Foundry Alfe CHEM has created a new product which represents a breakthrough in the class of HFC hydraulic fluids: Ecosafe Plus is a biodegradable fire-resistant hydraulic fluid with high engineering and technological performances, high environmental sustainability and the best security guarantees in workplaces. Its formulation is glycols-free, and it allows for easier disposal of the exhausted fluid, compared to a traditional water/ glycol-based HFC hydraulic fluid. For what concern the technological properties, Ecosafe Plus has been tested by accredited laboratories with tribological trials (4 Ball wear test ASTM D 4172, Ball on disc test ASTM 6425, Brugger test DIN 51347, Vickers test ASTM D 2882, with elastomer compatibility test (ASTM D 471 and biodegradability test (OECD 310 F.

  14. Sustainable Procurement

    DEFF Research Database (Denmark)

    Telles, Pedro; Ølykke, Grith Skovgaard

    2017-01-01

    and within it how sustainable requirements have increased the level of compliance required, particularly regulatory compliance. Compliance was already present in previous EU public procurement frameworks, but its extent on Directive 2014/24/EU leads the authors to consider the current legal framework...... as subject to substantial regulatory compliance obligations external to the process of procurement. In short, procurement has been transformed in a way to enforce regulatory obligations that are not intrinsic to the process of buying. This leads to the conclusion that questions such as the cost and trade...

  15. Transforming Growth Factor-β1 (TGF-β1 Induces Mouse Precartilaginous Stem Cell Proliferation through TGF-β Receptor II (TGFRII-Akt-β-Catenin Signaling

    Directory of Open Access Journals (Sweden)

    Li Cheng

    2014-07-01

    Full Text Available Precartilaginous stem cells (PSCs could self-renew or differentiate into chondrocytes to promote bone growth. In the current study, we aim to understand the role of transforming growth factor-β1 (TGF-β1 in precartilaginous stem cell (PSC proliferation, and to study the underlying mechanisms. We successfully purified and primary-cultured PSCs from the neonate mice’ perichondrial mesenchyme, and their phenotype was confirmed by the PSC marker fibroblast growth factor receptor-3 (FGFR-3 overexpression. We found that TGF-β1 induced Akt-glycogen synthase kinase-3β (GSK3β phosphorylation and β-catenin nuclear translocation in the mouse PSCs, which was almost blocked by TGF-β receptor-II (TGFRII shRNA knockdown. Further, perifosine and MK-2206, two Akt-specific inhibitors, suppressed TGF-β1-induced GSK3β phosphorylation and β-catenin nuclear translocation. Akt inhibitors, as well as β-catenin shRNA knockdown largely inhibited TGF-β1-stimulated cyclin D1/c-myc gene transcription and mouse PSC proliferation. Based on these results, we suggest that TGF-β1 induces Akt activation to promote β-catenin nuclear accumulation, which then regulates cyclin D1/c-myc gene transcription to eventually promote mouse PSC proliferation.

  16. Sustainable consumption and marketing

    NARCIS (Netherlands)

    Dam, van Y.K.

    2016-01-01

    Sustainable development in global food markets is hindered by the discrepancy between positive consumer attitudes towards sustainable development or sustainability and the lack of corresponding sustainable consumption by a majority of consumers. Apparently for many (light user) consumers the

  17. Sustainable IT and IT for Sustainability

    Science.gov (United States)

    Liu, Zhenhua

    Energy and sustainability have become one of the most critical issues of our generation. While the abundant potential of renewable energy such as solar and wind provides a real opportunity for sustainability, their intermittency and uncertainty present a daunting operating challenge. This thesis aims to develop analytical models, deployable algorithms, and real systems to enable efficient integration of renewable energy into complex distributed systems with limited information. The first thrust of the thesis is to make IT systems more sustainable by facilitating the integration of renewable energy into these systems. IT represents the fastest growing sectors in energy usage and greenhouse gas pollution. Over the last decade there are dramatic improvements in the energy efficiency of IT systems, but the efficiency improvements do not necessarily lead to reduction in energy consumption because more servers are demanded. Further, little effort has been put in making IT more sustainable, and most of the improvements are from improved "engineering" rather than improved "algorithms". In contrast, my work focuses on developing algorithms with rigorous theoretical analysis that improve the sustainability of IT. In particular, this thesis seeks to exploit the flexibilities of cloud workloads both (i) in time by scheduling delay-tolerant workloads and (ii) in space by routing requests to geographically diverse data centers. These opportunities allow data centers to adaptively respond to renewable availability, varying cooling efficiency, and fluctuating energy prices, while still meeting performance requirements. The design of the enabling algorithms is however very challenging because of limited information, non-smooth objective functions and the need for distributed control. Novel distributed algorithms are developed with theoretically provable guarantees to enable the "follow the renewables" routing. Moving from theory to practice, I helped HP design and implement

  18. A novel mechanism for Ca2+/calmodulin-dependent protein kinase II targeting to L-type Ca2+channels that initiates long-range signaling to the nucleus.

    Science.gov (United States)

    Wang, Xiaohan; Marks, Christian R; Perfitt, Tyler L; Nakagawa, Terunaga; Lee, Amy; Jacobson, David A; Colbran, Roger J

    2017-10-20

    Neuronal excitation can induce new mRNA transcription, a phenomenon called excitation-transcription (E-T) coupling. Among several pathways implicated in E-T coupling, activation of voltage-gated L-type Ca 2+ channels (LTCCs) in the plasma membrane can initiate a signaling pathway that ultimately increases nuclear CREB phosphorylation and, in most cases, expression of immediate early genes. Initiation of this long-range pathway has been shown to require recruitment of Ca 2+ -sensitive enzymes to a nanodomain in the immediate vicinity of the LTCC by an unknown mechanism. Here, we show that activated Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) strongly interacts with a novel binding motif in the N-terminal domain of Ca V 1 LTCC α1 subunits that is not conserved in Ca V 2 or Ca V 3 voltage-gated Ca 2+ channel subunits. Mutations in the Ca V 1.3 α1 subunit N-terminal domain or in the CaMKII catalytic domain that largely prevent the in vitro interaction also disrupt CaMKII association with intact LTCC complexes isolated by immunoprecipitation. Furthermore, these same mutations interfere with E-T coupling in cultured hippocampal neurons. Taken together, our findings define a novel molecular interaction with the neuronal LTCC that is required for the initiation of a long-range signal to the nucleus that is critical for learning and memory. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Selective attention and the auditory vertex potential. I - Effects of stimulus delivery rate. II - Effects of signal intensity and masking noise

    Science.gov (United States)

    Schwent, V. L.; Hillyard, S. A.; Galambos, R.

    1976-01-01

    The effects of varying the rate of delivery of dichotic tone pip stimuli on selective attention measured by evoked-potential amplitudes and signal detectability scores were studied. The subjects attended to one channel (ear) of tones, ignored the other, and pressed a button whenever occasional targets - tones of a slightly higher pitch were detected in the attended ear. Under separate conditions, randomized interstimulus intervals were short, medium, and long. Another study compared the effects of attention on the N1 component of the auditory evoked potential for tone pips presented alone and when white noise was added to make the tones barely above detectability threshold in a three-channel listening task. Major conclusions are that (1) N1 is enlarged to stimuli in an attended channel only in the short interstimulus interval condition (averaging 350 msec), (2) N1 and P3 are related to different modes of selective attention, and (3) attention selectivity in multichannel listening task is greater when tones are faint and/or difficult to detect.

  20. Complimentary aspects of diffusion imaging and fMRI: II. Elucidating contributions to the fMRI signal with diffusion sensitization.

    Science.gov (United States)

    Mulkern, Robert V; Haker, Steven J; Maier, Stephan E

    2007-07-01

    Tissue water molecules reside in different biophysical compartments. For example, water molecules in the vasculature reside for variable periods of time within arteries, arterioles, capillaries, venuoles and veins, and may be within blood cells or blood plasma. Water molecules outside of the vasculature, in the extravascular space, reside, for a time, either within cells or within the interstitial space between cells. Within these different compartments, different types of microscopic motion that water molecules may experience have been identified and discussed. These range from Brownian diffusion to more coherent flow over the time scales relevant to functional magnetic resonance imaging (fMRI) experiments, on the order of several 10s of milliseconds. How these different types of motion are reflected in magnetic resonance imaging (MRI) methods developed for "diffusion" imaging studies has been an ongoing and active area of research. Here we briefly review the ideas that have developed regarding these motions within the context of modern "diffusion" imaging techniques and, in particular, how they have been accessed in attempts to further our understanding of the various contributions to the fMRI signal changes sought in studies of human brain activation.

  1. Hydrogen protects against hyperoxia-induced apoptosis in type II alveolar epithelial cells via activation of PI3K/Akt/Foxo3a signaling pathway.

    Science.gov (United States)

    Wu, Dan; Liang, Mulin; Dang, Hongxing; Fang, Fang; Xu, Feng; Liu, Chengjun

    2018-01-08

    Oxidative stress is regarded as a key regulator in the pathogenesis of prolonged hyperoxia-induced lung injury, which causes injury to alveolar epithelial cells and eventually leads to development of bronchopulmonary dysplasia (BPD). Many studies have shown that hydrogen has a protective effect in a variety of cells. However, the mechanisms by which hydrogen rescues cells from damage due to oxidative stress in BPD remains to be fully elucidated. This study sought to evaluate the effects of hydrogen on hyperoxia-induced lung injury and to investigate the underlying mechanism. Primary type II alveolar epithelial cells (AECIIs) were divided into four groups: control (21% oxygen), hyperoxia (95% oxygen), hyperoxia + hydrogen, and hyperoxia + hydrogen + LY294002 (a PI3K/Akt inhibitor). Proliferation and apoptosis of AECIIs were assessed using MTS assay and flow cytometry (FCM), respectively. Gene and protein expression were detected by quantitative polymerase chain reaction (q-PCR) and western blot analysis. Stimulation with hyperoxia decreased the expression of P-Akt, P- FoxO3a, cyclinD1 and Bcl-2. Hyperoxic conditions increased levels of Bim, Bax, and Foxo3a, which induced proliferation restriction and apoptosis of AECIIs. These effects of hyperoxia were reversed with hydrogen pretreatment. Furthermore, the protective effects of hydrogen were abrogated by PI3K/Akt inhibitor LY294002. The results indicate that hydrogen protects AECIIs from hyperoxia-induced apoptosis by inhibiting apoptosis factors and promoting the expression of anti-apoptosis factors. These effects were associated with activation of the PI3K/Akt/FoxO3a pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Regulation of intracellular signaling cascades by GNRH pulse frequency in the rat pituitary: roles for CaMK II, ERK, and JNK activation.

    Science.gov (United States)

    Burger, Laura L; Haisenleder, Daniel J; Aylor, Kevin W; Marshall, John C

    2008-11-01

    Pulsatile GnRH (GNRH) differentially regulates LH and FSH subunit genes, with faster frequencies favoring Lhb transcription and slower favoring Fshb. Various intracellular pathways mediate the effects of GNRH, including CaMK II (CAMK2), ERK, and JNK. We examined whether activation of these pathways is regulated by GNRH pulse frequency in vivo. GNRH-deficient rats received GNRH pulses (25 ng i.v. every 30 or 240 min for 8 h, vehicle to controls). Pituitaries were collected 5 min after the last pulse, bisected, and one half processed for RNA (to measure beta subunit primary transcripts [PTs]) and the other for protein. Phosphorylated CAMK2 (phospho-CAMK2), ERK (mitogen-activated protein kinase 1/3 [MAPK1/3], also known as p42 ERK2 and p44 ERK1, respectively), and JNK (MAPK8/9, also known as p46 JNK1 and p54 JNK2, respectively) were determined by Western blotting. The 30-min pulses maximally stimulated Lhb PT (8-fold), whereas 240 min was optimal for Fshb PT (3-fold increase). Both GNRH pulse frequencies increased phospho-CAMK2 4-fold. Activation of MAPK1/3 was stimulated by both 30- and 240-min pulses, but phosphorylation of MAPK3 was significantly greater following slower GNRH pulses (240 min: 4-fold, 30 min: 2-fold). MAPK8/9 activation was unchanged by pulsatile GNRH in this paradigm, but as previous results showed that GNRH-induced activation of MAPK8/9 is delayed, 5 min after GNRH may not be optimal to observe MAPK8/9 activation. These data show that CAMK2 is activated by GNRH, but not in a frequency-dependant manner, whereas MAPK3 is maximally stimulated by slow-frequency GNRH pulses. Thus, the ERK response to slow pulse frequency is part of the mechanisms mediating Fhb transcriptional responses to GNRH.

  3. Regulation of Intracellular Signaling Cascades by GNRH Pulse Frequency in the Rat Pituitary: Roles for CaMK II, ERK, and JNK Activation1

    Science.gov (United States)

    Burger, Laura L.; Haisenleder, Daniel J.; Aylor, Kevin W.; Marshall, John C.

    2008-01-01

    Pulsatile GnRH (GNRH) differentially regulates LH and FSH subunit genes, with faster frequencies favoring Lhb transcription and slower favoring Fshb. Various intracellular pathways mediate the effects of GNRH, including CaMK II (CAMK2), ERK, and JNK. We examined whether activation of these pathways is regulated by GNRH pulse frequency in vivo. GNRH-deficient rats received GNRH pulses (25 ng i.v. every 30 or 240 min for 8 h, vehicle to controls). Pituitaries were collected 5 min after the last pulse, bisected, and one half processed for RNA (to measure beta subunit primary transcripts [PTs]) and the other for protein. Phosphorylated CAMK2 (phospho-CAMK2), ERK (mitogen-activated protein kinase 1/3 [MAPK1/3], also known as p42 ERK2 and p44 ERK1, respectively), and JNK (MAPK8/9, also known as p46 JNK1 and p54 JNK2, respectively) were determined by Western blotting. The 30-min pulses maximally stimulated Lhb PT (8-fold), whereas 240 min was optimal for Fshb PT (3-fold increase). Both GNRH pulse frequencies increased phospho-CAMK2 4-fold. Activation of MAPK1/3 was stimulated by both 30- and 240-min pulses, but phosphorylation of MAPK3 was significantly greater following slower GNRH pulses (240 min: 4-fold, 30 min: 2-fold). MAPK8/9 activation was unchanged by pulsatile GNRH in this paradigm, but as previous results showed that GNRH-induced activation of MAPK8/9 is delayed, 5 min after GNRH may not be optimal to observe MAPK8/9 activation. These data show that CAMK2 is activated by GNRH, but not in a frequency-dependant manner, whereas MAPK3 is maximally stimulated by slow-frequency GNRH pulses. Thus, the ERK response to slow pulse frequency is part of the mechanisms mediating Fhb transcriptional responses to GNRH.. PMID:18716286

  4. Managed Sustainable Development Classification Of Resources And Goods amp Services Calculating Sustainable Growth Rate And The Sustainable Development Index

    Directory of Open Access Journals (Sweden)

    Shubham Saxena

    2017-05-01

    Full Text Available Macro-level manmade problems can often be best solved by understanding and manipulating the economics behind it. The world today is facing genuine problems of scarcity of resources and environmental amp ecological issues in view of intergenerational equity. The paper proposes a new approach of identification and classification of i Resources and ii Goods and services in the context of sustainable development. Every economy has ambitious economic growth aspirations which are often found conflicting with the commitments on natural resource conservation and climate change obligations. The proposed methodology is a reconciliation of the aspired economic growth of a region and the conservation of the resources and nature. The paper employs contribution of different types of goods and services in the gross domestic product GDP of a region to analyze sustainability of development. The important parameters that the paper establishes are Sustainability Ratio R Sustainable Growth Rate SG and the Sustainable Development Index SI. These parameters can be used to compare the sustainable development level of different regions. Ensuring natural resource and environmental sustainability will eventually ensure economic sustainability. The paper considers resource depletion concerns as well as the environmental pollutants biological risks carbon footprint warhead proliferation et cetera thereby ensuring all round sustainability from survival to economic end. The sustainability analysis is done for long periods such as 50 years 100 years et cetera. The index shows how sustainable the development of an economy is and how sustainability it is growing. The presently much revered GDP growth numbers are directionless it does not tell the type of growth an economy essentially has. The direction should be sustainability which the paper stresses upon. An illustration of sustainability analysis of India is also done. Such indices can help identifying sustainably developing

  5. Sulforaphane protects H9c2 cardiomyocytes from angiotensin II-induced hypertrophy.

    Science.gov (United States)

    Wu, Q-Q; Zong, J; Gao, L; Dai, J; Yang, Z; Xu, M; Fang, Y; Ma, Z-G; Tang, Q-Z

    2014-05-01

    Cardiac hypertrophy is an adaptive process of the heart in response to various stimuli, but sustained cardiac hypertrophy will finally lead to heart failure. Sulforaphane-extracted from cruciferous vegetables of the genus Brassica such as broccoli, brussels sprouts, and cabbage-has been evaluated for its anticarcinogenic and antioxidant effects. To investigate the effect of sulforaphane on angiotensin II (Ang II)-induced cardiac hypertrophy in vitro. Embryonic rat heart-derived H9c2 cells were co-incubated with sulforaphane and Ang II. The cell surface area and mRNA levels of hypertrophic markers were measured to clarify the effect of sulforaphane on cardiac hypertrophy. The underlying mechanism was further investigated by detecting the activation of Akt and NF-κB signaling pathways. We found that H9c2 cells pretreated with sulforaphane were protected from Ang II-induced hypertrophy. The increasing mRNA levels of ANP, BNP, and β-MHC in Ang II-stimulated cells were also down-regulated after sulforaphane treatment. Moreover, sulforaphane repressed the Ang II-induced phosphorylation of Akt, GSK3β, mTOR, eIF4e, as well as of IκBα and NF-κB. Based on our results, sulforaphane attenuates Ang II-induced hypertrophy of H9c2 cardiomyocytes mediated by the inhibition of intracellular signaling pathways including Akt and NF-κB.

  6. Virtual Sustainability

    Directory of Open Access Journals (Sweden)

    William Sims Bainbridge

    2010-09-01

    Full Text Available In four ways, massively multiplayer online role-playing games may serve as tools for advancing sustainability goals, and as laboratories for developing alternatives to current social arrangements that have implications for the natural environment. First, by moving conspicuous consumption and other usually costly status competitions into virtual environments, these virtual worlds might reduce the need for physical resources. Second, they provide training that could prepare individuals to be teleworkers, and develop or demonstrate methods for using information technology to replace much transportation technology, notably in commuting. Third, virtual worlds and online games build international cooperation, even blending national cultures, thereby inching us toward not only the world consciousness needed for international agreements about the environment, but also toward non-spatial government that cuts across archaic nationalisms. Finally, realizing the potential social benefits of this new technology may urge us to reconsider a number of traditional societal institutions.

  7. Sustainability; Sustentabilidade

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    This chapter analyses the production chain of ethanol, considering the impacts on the quality of the air, water supplies, soil occupation and biodiversity, and the efforts for the soil preservation. It is pointed out the activities of the production cycle and use of bio ethanol due to great uncertainties as far the environmental impacts is concerning and that will deserve more attention in future evaluations. At same time, the chapter highlights another activities where the present acknowledge is sufficient to assure the control and/or prediction of consequences of the desired intervention on the environment media to accommodate the sugar and ethanol production expansion. The consideration is not conservative but to promote the sustainable development.

  8. Sustainability Science Needs Sustainable Data!

    Science.gov (United States)

    Downs, R. R.; Chen, R. S.

    2013-12-01

    Sustainability science (SS) is an 'emerging field of research dealing with the interactions between natural and social systems, and with how those interactions affect the challenge of sustainability: meeting the needs of present and future generations while substantially reducing poverty and conserving the planet's life support systems' (Kates, 2011; Clark, 2007). Bettencourt & Kaur (2011) identified more than 20,000 scientific papers published on SS topics since the 1980s with more than 35,000 distinct authors. They estimated that the field is currently growing exponentially, with the number of authors doubling approximately every 8 years. These scholars are undoubtedly using and generating a vast quantity and variety of data and information for both SS research and applications. Unfortunately we know little about what data the SS community is actually using, and whether or not the data that SS scholars generate are being preserved for future use. Moreover, since much SS research is conducted by cross-disciplinary, multi-institutional teams, often scattered around the world, there could well be increased risks of data loss, reduced data quality, inadequate documentation, and poor long-term access and usability. Capabilities and processes therefore need to be established today to support continual, reliable, and efficient preservation of and access to SS data in the future, especially so that they can be reused in conjunction with future data and for new studies not conceived in the original data collection activities. Today's long-term data stewardship challenges include establishing sustainable data governance to facilitate continuing management, selecting data to ensure that limited resources are focused on high priority SS data holdings, securing sufficient rights to allow unforeseen uses, and preparing data to enable use by future communities whose specific research and information needs are not yet known. Adopting sustainable models for archival

  9. Advancing sustainable development in Canada : policy issues and research needs[PRI Project, Sustainable Development

    Energy Technology Data Exchange (ETDEWEB)

    Eliadis, P. [Government of Canada Privy Council Office, Ottawa, ON (Canada). Policy Research Initiative; Creech, H.; Glanville, B.; Barg, S.; Cosbey, A.; Roy, M.; Swanson, D.A.; Venema, H.D.; Von Moltke, K. [International Inst. for Sustainable Development, Winnipeg, MB (Canada); Slayen, S. (ed.)

    2003-11-01

    This paper defined 7 policy-relevant issues that advance sustainable development in Canada. These were; (1) urban redesign, (2) freshwater management, (3) eco-region sustainability, (4) impacts of globalization on sustainable development in Canada, (5) designing signals and incentives that promote sustainable behaviour among citizens, (6) reducing the ecological burden of unsustainable lifestyles, and (7) international engagement in sustainable development. The authors questioned why these issues have not made greater progress, given that they have been on national and international agendas since 1972. They also questioned why it is so difficult to integrate environmental and economic signals. Finally, they examined whether enough ecological and political space can be provided to developing countries to achieve sustainable development while enhancing the standard of living in Canada and not threatening critical global systems. 173 refs.

  10. Enhanced and sustained CD8+ T cell responses with an adenoviral vector-based hepatitis C virus vaccine encoding NS3 linked to the MHC class II chaperone protein invariant chain

    DEFF Research Database (Denmark)

    Mikkelsen, Marianne; Holst, Peter Johannes; Bukh, Jens

    2011-01-01

    memory. Functionally, the AdIiNS3-vaccinated mice had a significantly increased cytotoxic capacity compared with the AdNS3 group. The AdIiNS3-induced CD8(+) T cells protected mice from infection with recombinant vaccinia virus expressing HCV NS3 of heterologous 1b strains, and studies in knockout mice...

  11. Activity Dependent Signal Transduction in Skeletal Muscle

    Science.gov (United States)

    Hamilton, Susan L.

    1999-01-01

    The overall goals of this project are: 1) to define the initial signal transduction events whereby the removal of gravitational load from antigravity muscles, such as the soleus, triggers muscle atrophy, and 2) to develop countermeasures to prevent this from happening. Our rationale for this approach is that, if countermeasures can be developed to regulate these early events, we could avoid having to deal with the multiple cascades of events that occur downstream from the initial event. One of our major findings is that hind limb suspension causes an early and sustained increase in intracellular Ca(2+) concentration ([Ca (2+)](sub i)). In most cells the consequences of changes in ([Ca (2+)](sub i))depend on the amplitude, frequency and duration of the Ca(2+) signal and on other factors in the intracellular environment. We propose that muscle remodeling in microgravity represents a change in the balance among several CA(2+) regulated signal transduction pathways, in particular those involving the transcription factors NFAT and NFkB and the pro-apoptotic protein BAD. Other Ca(2+) sensitive pathways involving PKC, ras, rac, and CaM kinase II may also contribute to muscle remodeling.

  12. Signal Words

    Science.gov (United States)

    SIGNAL WORDS TOPIC FACT SHEET NPIC fact sheets are designed to answer questions that are commonly asked by the ... making decisions about pesticide use. What are Signal Words? Signal words are found on pesticide product labels, ...

  13. Sustainable agriculture - selected papers

    OpenAIRE

    Krasowicz, Stanisław; Wrzaszcz, Wioletta; Zegar, Jozef St.

    2007-01-01

    The concept of research on socially sustainable agriculture. Features of sustainable agriculture. Sustainability of private farms in the light of selected criteria. Subsistence agricultural holdings and the sustainable development of agriculture. Sustainable farms in the light of the FADN data. Description of organic holdings in Poland.

  14. Sustainable NREL - Site Sustainability Plan FY 2015

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2015-01-01

    NREL's Site Sustainability Plan FY 2015 reports on sustainability plans for the lab for the year 2015 based on Executive Order Goals and provides the status on planned actions cited in the FY 2014 report.

  15. Performance sustaining intracortical neural prostheses

    Science.gov (United States)

    Nuyujukian, Paul; Kao, Jonathan C.; Fan, Joline M.; Stavisky, Sergey D.; Ryu, Stephen I.; Shenoy, Krishna V.

    2014-12-01

    Objective. Neural prostheses, or brain-machine interfaces, aim to restore efficient communication and movement ability to those suffering from paralysis. A major challenge these systems face is robust performance, particularly with aging signal sources. The aim in this study was to develop a neural prosthesis that could sustain high performance in spite of signal instability while still minimizing retraining time. Approach. We trained two rhesus macaques implanted with intracortical microelectrode arrays 1-4 years prior to this study to acquire targets with a neurally-controlled cursor. We measured their performance via achieved bitrate (bits per second, bps). This task was repeated over contiguous days to evaluate the sustained performance across time. Main results. We found that in the monkey with a younger (i.e., two year old) implant and better signal quality, a fixed decoder could sustain performance for a month at a rate of 4 bps, the highest achieved communication rate reported to date. This fixed decoder was evaluated across 22 months and experienced a performance decline at a rate of 0.24 bps yr-1. In the monkey with the older (i.e., 3.5 year old) implant and poorer signal quality, a fixed decoder could not sustain performance for more than a few days. Nevertheless, performance in this monkey was maintained for two weeks without requiring additional online retraining time by utilizing prior days’ experimental data. Upon analysis of the changes in channel tuning, we found that this stability appeared partially attributable to the cancelling-out of neural tuning fluctuations when projected to two-dimensional cursor movements. Significance. The findings in this study (1) document the highest-performing communication neural prosthesis in monkeys, (2) confirm and extend prior reports of the stability of fixed decoders, and (3) demonstrate a protocol for system stability under conditions where fixed decoders would otherwise fail. These improvements to decoder

  16. Sustainability in Transport Planning

    DEFF Research Database (Denmark)

    Gudmundsson, Henrik; Greve, Carsten

    Contribution to session J: Joint University Sustainability Initiatives. This session will provide an inspiring overview of interdisciplinary research and teaching activities on sustainability bridging DTU, KU, and CBS, and introduce the joint collaboration Copenhagen Sustainability Initiative (COSI...

  17. Sustainability : Politics and governance

    NARCIS (Netherlands)

    Heinrichs, Harald; Biermann, Frank

    2016-01-01

    he article gives an overview of global sustainability policy and politics. It is shown how international policy making on sustainable development has progressed from environmental policy toward recent approaches of Earth system governance. Key challenges of international sustainability politics are

  18. Textiles and clothing sustainability sustainable technologies

    CERN Document Server

    2017-01-01

    This is the first book to deal with the innovative technologies in the field of textiles and clothing sustainability. It details a number of sustainable and innovative technologies and highlights their implications in the clothing sector. There are currently various measures to achieve sustainability in the textiles and the clothing industry, including innovations in the manufacturing stage, which is the crux of this book.

  19. Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

    Energy Technology Data Exchange (ETDEWEB)

    Chapman, S. C., E-mail: S.C.Chapman@warwick.ac.uk [Centre for Fusion, Space and Astrophysics, Department of Physics, University of Warwick, Coventry (United Kingdom); Max Planck Institute for the Physics of Complex Systems, Dresden (Germany); Dendy, R. O. [Centre for Fusion, Space and Astrophysics, Department of Physics, University of Warwick, Coventry (United Kingdom); Euratom/CCFE Fusion Association, Culham Science Centre, Abingdon, Oxfordshire (United Kingdom); JET-EFDA, Culham Science Centre, Abingdon, Oxfordshire (United Kingdom); Todd, T. N.; Webster, A. J.; Morris, J. [Euratom/CCFE Fusion Association, Culham Science Centre, Abingdon, Oxfordshire (United Kingdom); JET-EFDA, Culham Science Centre, Abingdon, Oxfordshire (United Kingdom); Watkins, N. W. [Centre for Fusion, Space and Astrophysics, Department of Physics, University of Warwick, Coventry (United Kingdom); Max Planck Institute for the Physics of Complex Systems, Dresden (Germany); Centre for the Analysis of Time Series, London School of Economics, London (United Kingdom); Department of Engineering and Innovation, Open University, Milton Keynes (United Kingdom); Calderon, F. A. [Centre for Fusion, Space and Astrophysics, Department of Physics, University of Warwick, Coventry (United Kingdom); JET-EFDA, Culham Science Centre, Abingdon, Oxfordshire (United Kingdom)

    2014-06-15

    A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM.

  20. PSSD - Planning System for Sustainable Development

    DEFF Research Database (Denmark)

    PSSD - Planning System for Sustainable Development - is a part of the Baltic Sea Region's INTERREG II C program. The current report describes some theories, methods and tools developed under the PSSD project. First, the theoretical foundation of the project is described. Secondly, the role...... of indicators in sustainable development is discussed and a Web-based indicator generator is described. Thirdly, we describe a number of methods and tools, which support planning for sustainable development. Finally, some technical interface tools - especially a Web-based interface to the methods and tools...

  1. Merlin, a regulator of Hippo signaling, regulates Wnt/β-catenin signaling.

    Science.gov (United States)

    Kim, Soyoung; Jho, Eek-Hoon

    2016-07-01

    Merlin, encoded by the NF2 gene, is a tumor suppressor that exerts its function via inhibiting mitogenic receptors at the plasma membrane. Although multiple mutations in Merlin have been identified in Neurofibromatosis type II (NF2) disease, its molecular mechanism is not fully understood. Here, we show that Merlin interacts with LRP6 and inhibits LRP6 phosphorylation, a critical step for the initiation of Wnt signaling. We found that treatment of Wnt3a caused phosphorylation of Merlin by PAK1, leading to detachment of Merlin from LRP6 and allowing the initiation of Wnt/β-catenin signaling. A higher level of β-catenin was found in tissues from NF2 patients. Enhanced proliferation and migration caused by knockdown of Merlin in glioblastoma cells were inhibited by suppression of β-catenin. Conclusively, these results suggest that sustained Wnt/β-catenin signaling activity induced by abrogation of Merlin-mediated inhibition of LRP6 phosphorylation might be a cause of NF2 disease. [BMB Reports 2016; 49(7): 357-358].

  2. Assessing sustainable remediation frameworks using sustainability principles.

    Science.gov (United States)

    Ridsdale, D Reanne; Noble, Bram F

    2016-12-15

    The remediation industry has grown exponentially in recent decades. International organizations of practitioners and remediation experts have developed several frameworks for integrating sustainability into remediation projects; however, there has been limited attention to how sustainability is approached and operationalized in sustainable remediation frameworks and practices - or whether sustainability plays any meaningful role at all in sustainable remediation. This paper examines how sustainability is represented in remediation frameworks and the guidance provided for practical application. Seven broad sustainability principles and review criteria are proposed and applied to a sample of six international remediation frameworks. Not all review criteria were equally satisfied and none of the frameworks fully met all criteria; however, the best performing frameworks were those identified as sustainability remediation frameworks. Intra-generational equity was addressed by all frameworks. Integrating social, economic and biophysical components beyond triple-bottom-line indicators was explicitly addressed only by the sustainable remediation frameworks. No frameworks provided principle- or rule-based guidance for dealing with trade-offs in sustainability decisions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Organizing for Sustainability

    Science.gov (United States)

    Brown, William M.; Hamburger, Michael W.

    2012-01-01

    A successful campus sustainability effort catalyzes broad engagement of the campus community and integration of sustainability principles into the academic and operational components of campus life. Although many universities have embraced sustainability as a new core value, others have been more sluggish in adopting sustainability principles to…

  4. Technology and sustainability

    NARCIS (Netherlands)

    Kroeze, C.; Boersema, J.J.; Tellegen, E.; Cremers, A.

    2011-01-01

    In ten essays, this book addresses a broad range of issues related to the interplay of sustainability and technology. How do population growth and technology relate to sustainable development? Can globalization be reconciled with sustainable development? Is sustainability a subjective or an

  5. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    by analysing processes of social learning. The book addresses the need to move towards sustainability at societal level as a democratic challenge questioning the way we live on planet earth. By conceptualising sustain-ability as an immanent and emergent ability of ecological and social life, continuously...... to renew itself without eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming...

  6. Sustainable Investment. Literature Overview

    Energy Technology Data Exchange (ETDEWEB)

    Weda, J.; Kerste, M.; Rosenboom, N.

    2010-08-15

    Corporate Social Responsibility (CSR), or sustainability at the company level, entails incorporating ecological (environmental stakeholders) and social aspects (stakeholders other than shareholders and environmental stakeholders) when doing business. Socially Responsible Investment (SRI) concerns sustainability at the investment, fund or portfolio level and involves screening the sustainability of companies before investing in them. This report highlights leading literature and empirical findings on 'sustainable investment', amongst others addressing the economic rationale for CSR and SRI. This report is part of a set of SEO-reports on finance and sustainability. The other reports deal with: Financing the Transition to Sustainable Energy; Carbon Trading; Innovations in financing environmental and social sustainability.

  7. Promoting implementation of sustainable development goals in rural ...

    African Journals Online (AJOL)

    Promoting implementation of sustainable development goals in rural Nigeria: II food security issues and their determinants among cassava-based farming households in Akpabuyo Local Government Area, Cross River State, Nigeria.

  8. (II) complexes

    African Journals Online (AJOL)

    activities of Schiff base tin (II) complexes. Neelofar1 ... Conclusion: All synthesized Schiff bases and their Tin (II) complexes showed high antimicrobial and ...... Singh HL. Synthesis and characterization of tin (II) complexes of fluorinated Schiff bases derived from amino acids. Spectrochim Acta Part A: Molec Biomolec.

  9. Effective Assessment Framework: Sustainability of Post Amnesty ...

    African Journals Online (AJOL)

    To proffer solution, Federal government came up with post-amnesty program. Based on this, the study sought; (i) To determine the level of effectiveness of the implementation of the Post Amnesty Programme since its inception in 2009, (ii) determine how effective evaluation method can sustain Post Amnesty programme ...

  10. USAF Logistics Process Optimization Study for the Aircraft Asset Sustainment Process. Volume 3. Future to be Asset Sustainment Process Model

    National Research Council Canada - National Science Library

    Adamson, Anthony

    1998-01-01

    .... It is published as three separate volumes. Volume I, USAF Logistics Process Optimization Study for the Aircraft Asset Sustainment Process -- Phase II Report, discusses the result and cost/benefit analysis of testing three initiatives...

  11. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    How can action research further new research orientations towards sustainability? This book, empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating on urban sustainability, answers this question...... by analysing processes of social learning. The book addresses the need to move towards sustainability at societal level as a democratic challenge questioning the way we live on planet earth. By conceptualising sustain-ability as an immanent and emergent ability of ecological and social life, continuously...... to renew itself without eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming...

  12. Sustaining Rural Communities through Sustainable Agriculture.

    Science.gov (United States)

    Ikerd, John

    A 5-year collaborative project between Missouri, Michigan State, and Nebraska Universities to provide new opportunities for rural community self-development through sustainable agriculture had mixed results. This happened because community members did not understand the principles of sustainability, and because the extension education system was…

  13. Can We Sustainably Harvest Ivory?

    Science.gov (United States)

    Lusseau, David; Lee, Phyllis C

    2016-11-07

    Despite the 1989 ivory trade ban, elephants continue to be killed to harvest their tusks for ivory. Since 2008, this poaching has increased to unprecedented levels driven by consumer demand for ivory products. CITES is now considering the development of a legal ivory trade [1, 2]. The proposal relies on three assumptions: (1) harvest regulation will cease all illegal activities, (2) defined sustainable quotas can be enforced, and (3) we can define meaningful sustainable quotas that come close to the current demand. We know that regulation of harvest does not stop illegal takes. Despite whaling regulation after World War II, illegal whaling continued for decades [3]. The introduction of wolf culls in the US actually increased poaching activities [4], and one-off ivory sales in 1999 and 2008 did nothing to halt elephant poaching. Governance issues over the ivory supply chains, including stockpiling, make enforcing quotas challenging, if not impossible [5, 6]. We have not yet adequately assessed what could be a sustainable ivory yield. To do so, we develop a compartmental model composed of a two-sex age-structured demographic model and an ivory production and harvest model. We applied several offtake and quota strategies to define how much ivory could be sustainably harvested. We found that the sustainability space is very small. Only 100 to 150 kg of ivory could be removed from a reference population of 1,360 elephants, levels well below the current demand. Our study shows that lifting the ivory ban will not address the current poaching challenge. We should instead focus on reducing consumer demand. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Sustainable Marketing : The Importance of Being a Sustainable Business

    OpenAIRE

    Reutlinger, Janina

    2012-01-01

    This thesis deals with sustainable marketing, as well as the necessity for more sustainability. The purpose of this thesis was to determine the importance of sustainable marketing for companies. The theoretical part is divided into sustainability and sustainable marketing. Sustainability covers current issues and sustainable development, which form a background for a better understanding of sustainable marketing. Sustainable marketing includes a definition of the concept, as well as susta...

  15. Invariant Chain Complexes and Clusters as Platforms for MIF Signaling

    Directory of Open Access Journals (Sweden)

    Robert Lindner

    2017-02-01

    Full Text Available Invariant chain (Ii/CD74 has been identified as a surface receptor for migration inhibitory factor (MIF. Most cells that express Ii also synthesize major histocompatibility complex class II (MHC II molecules, which depend on Ii as a chaperone and a targeting factor. The assembly of nonameric complexes consisting of one Ii trimer and three MHC II molecules (each of which is a heterodimer has been regarded as a prerequisite for efficient delivery to the cell surface. Due to rapid endocytosis, however, only low levels of Ii-MHC II complexes are displayed on the cell surface of professional antigen presenting cells and very little free Ii trimers. The association of Ii and MHC II has been reported to block the interaction with MIF, thus questioning the role of surface Ii as a receptor for MIF on MHC II-expressing cells. Recent work offers a potential solution to this conundrum: Many Ii-complexes at the cell surface appear to be under-saturated with MHC II, leaving unoccupied Ii subunits as potential binding sites for MIF. Some of this work also sheds light on novel aspects of signal transduction by Ii-bound MIF in B-lymphocytes: membrane raft association of Ii-MHC II complexes enables MIF to target Ii-MHC II to antigen-clustered B-cell-receptors (BCR and to foster BCR-driven signaling and intracellular trafficking.

  16. Signaling aggression.

    Science.gov (United States)

    van Staaden, Moira J; Searcy, William A; Hanlon, Roger T

    2011-01-01

    From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    Analysing processes of social learning this work addresses how action research can further new research orientations towards sustainability. Empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating...... on urban sustainability the need to move towards sustainability at societal level is conceptualised as a democratic challenge questioning the way we live on planet earth. By understanding sustainability as an immanent and emergent ability of ecological and social life, continuously to renew itself without...... eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming to provide local citizens...

  18. Handbook of sustainable engineering

    CERN Document Server

    Lee, Kun-Mo

    2013-01-01

    "The efficient utilization of energy, sustainable use of natural resources, and large-scale adoption of sustainable technologies is the key to a sustainable future. The Handbook of Sustainable Engineering provides tools that will help us achieve these goals". Nobel Prize Winner Dr. R.K. Pauchauri, Chairman, UN Intergovernmental Panel on Climate Change As global society confronts the challenges of diminishing resources, ecological degradation, and climate change, engineers play a crucial role designing and building technologies and products that fulfil our needs for utility and sustainability. The Handbook of Sustainable Engineering equips readers with the context and the best practices derived from both academic research and practical examples of successful implementations of sustainable technical solutions. The handbook’s content revolves around the two themes, new ways of thinking and new business models, including sustainable production, products, service systems and consumption while addressing key asse...

  19. FORUM: Is Ecotourism Sustainable?

    Science.gov (United States)

    Wall

    1997-07-01

    / It is legitimate to ask whether and in what form tourism might contribute to sustainable development. This is not the same as sustainable tourism which, as a single-sector approach to development, may overlook important linkages with other sectors. If tourism is to contribute to sustainable development, then it must be economically viable, ecologically sensitive and culturally appropriate. Ecotourism is often advocated as being a sustainable form of tourism but imprecision in terminology clouds basic issues and there are strong economic, ecological, and cultural reasons for believing that, even in its purest forms, ecotourism is likely to present substantial challenges to destination areas, particularly if it competes for scarce resources and displaces existing uses and users. Sustainable tourism and ecotourism are not synonyms, many forms of ecotourism may not be sustainable, and if ecotourism is to contribute to sustainable development, then careful planning and management will be required.KEY WORDS: Ecotourism; Sustainable development; Development; Tourism

  20. Livestock biodiversity and sustainability

    NARCIS (Netherlands)

    Hoffmann, I.

    2011-01-01

    Sustainable development equally includes environmental protection including biodiversity, economic growth and social equity, both within and between generations. The paper first reviews different aspects related to the sustainable use of livestock biodiversity and property regimes that influence

  1. Sustainable Public Bids

    Directory of Open Access Journals (Sweden)

    Gil César Costa de Paula

    2016-06-01

    Full Text Available In this article we will discuss the issue of sustainability in public procurement, given that the government in Brazil is constituted as a great promoter of economic development and needs to adapt its acquisitions worldwide sustainability agenda.

  2. Indicators for environmental sustainability

    DEFF Research Database (Denmark)

    Dong, Yan; Hauschild, Michael Zwicky

    2017-01-01

    . In this study, we reviewed indicators applied in life cycle assessment (LCA), planetary boundary framework (PB), and Sustainable Development Goals (SDGs) developed under United Nation. The aim is to 1) identify their applications and relevant decision context; 2) Review their indicators and categorize them......Decision making on sustainable consumption and production requires scientifically based information on sustainability. Different environmental sustainability targets exist for specific decision problems. To observe how well these targets are met, relevant environmental indicators are needed...

  3. Sustainable Learning Organizations

    Science.gov (United States)

    Velazquez, Luis E.; Esquer, Javier; Munguia, Nora E.; Moure-Eraso, Rafael

    2011-01-01

    Purpose: The purpose of this paper is to debate how companies may better become a sustainable learning organization by offering the most used and insightful concepts of sustainability. Design/methodology/approach: Through literature review, learning organization and sustainability perspectives are explored and compared. Findings: Learning…

  4. Measuring Educational Sustainability

    Science.gov (United States)

    Selvanathan, Rani G.

    2013-01-01

    There are many definitions that are attributable to the meaning of sustainability. Sustainability can be viewed as long-lasting, effective result of a project, venture, action, or investment without consuming additional future resources. Because of the wide nature of its applicability, a universal measure of sustainability is hard to come by. This…

  5. ORNL Annual Sustainability Report

    Energy Technology Data Exchange (ETDEWEB)

    Lapsa, Melissa Voss [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nichols, Teresa A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-02-01

    As described in this report, we have made substantial progress across the 25 roadmaps of the Sustainable Campus Initiative. The report also outlines our plans to continue integrating sustainable practices into the planning, execution, and evaluation of all ORNL activities. We appreciate your interest in our journey to sustainability, and we welcome your comments, questions, and suggestions.

  6. Toward sustainable logistics

    NARCIS (Netherlands)

    Soysal, Mehmet; Bloemhof-Ruwaard, Jacqueline M.

    2017-01-01

    The fast evolution of sustainability leads to the development of a new fast-growing concept called sustainable logistics management. This research addresses recent business trends and challenges in logistics and their implications for sustainable logistics management. Additionally, we discuss policy

  7. LCA and Sustainability

    DEFF Research Database (Denmark)

    Moltesen, Andreas; Bjørn, Anders

    2017-01-01

    LCA is often presented as a sustainability assessment tool. This chapter analyses the relationship between LCA and sustainability. This is done by first outlining the history of the sustainability concept, which gained momentum with the Brundtland Commission’s report ‘Our Common Future report ’ i...

  8. Lean maturity, lean sustainability

    DEFF Research Database (Denmark)

    Jørgensen, Frances; Matthiesen, Rikke; Nielsen, Jacob

    2007-01-01

    Although lean is rapidly growing in popularity, its implementation is far from problem free and companies may experience difficulties sustaining long term success. In this paper, it is suggested that sustainable lean requires attention to both performance improvement and capability development...... that support lean capability development and consequently, lean sustainability....

  9. Food sustainability: diverging interpretations

    NARCIS (Netherlands)

    Aiking, H.; de Boer, J.

    2004-01-01

    The concept of sustainability in general and food sustainability, in particular, entails many aspects and many interpretations. During a conference on food sustainability a broad, multidisciplinary picture was painted and many key issues were dealt with, from ecology, economy and society. In

  10. Transferring Education for Sustainability

    Science.gov (United States)

    Gafoor, Kunnathodi Abdul; Umer Farooque, T. K.

    2013-01-01

    Sustainability stands for sustaining the past, meeting needs of the present without compromising the ability to meet future needs. It should meet the individual and social needs, present and future needs local and global needs. A sustainable education that meets this requirements surely be a transferable education; an education that transfers from…

  11. Sustainability: An Overview.

    Science.gov (United States)

    Wormsley, W. E.

    1990-01-01

    This article introduces a group of six papers on sustainability of programs for visually handicapped persons in developing countries. Sustainability is discussed from an anthropological perspective, noting the importance of a social soundness analysis and a social impact assessment, enemies of sustainability, and the need for broad local input in…

  12. Sustainability in logistics practice

    NARCIS (Netherlands)

    Hans-Heinrich Glöckner; Reinder Pieters; Stef Weijers

    2009-01-01

    This conceptual paper wants to emphasis the use of the concept of sustainability within logistics and especially transportation. While working on a new tool to help companies develop sustainable European networks, we discovered that we want to use a specific concept of sustainability: People, planet

  13. Sustainability, Ethics and Nuclear Energy: Escaping the Dichotomy

    Directory of Open Access Journals (Sweden)

    Céline Kermisch

    2017-03-01

    Full Text Available In this paper we suggest considering sustainability as a moral framework based on social justice, which can be used to evaluate technological choices. In order to make sustainability applicable to discussions of nuclear energy production and waste management, we focus on three key ethical questions, namely: (i what should be sustained; (ii why should we sustain it; and (iii for whom should we sustain it. This leads us to conceptualize the notion of sustainability as a set of values, including safety, security, environmental benevolence, resource durability, and economic viability of the technology. The practical usefulness of sustainability as a moral framework is highlighted by demonstrating how it is applicable for understanding intergenerational dilemmas—between present and future generations, but also among different future generations—related to nuclear fuel cycles and radioactive waste management.

  14. Sustainable Development in the EU: Redefining and Operationalizing the Concept

    Directory of Open Access Journals (Sweden)

    Sander R.W. van Hees

    2014-05-01

    Full Text Available Although sustainable development plays an important role in EU law, neither EU law nor EU policy clearly explains what the concept means and how it must be put into practice. Policy-makers, NGOs, politicians and businesses do, however, need guidance on sustainable development for the purpose of good policy-making, for effectively holding the EU accountable, and for the design of CSR programmes. To that end, this article will first explain the guidance which EU law and policy already offer on sustainable development. Subsequently, this article will propose (I a more workable definition of sustainable development than the one (the Brundtland definition which is currently used, and (II a framework of application for sustainable development. This framework of application (which will have the form of a sustainability impact assessment provides practical guidance for policy-makers, politicians, NGOs and businesses when dealing with sustainable development in their day-to-day work.

  15. Ultrasound imaging using coded signals

    DEFF Research Database (Denmark)

    Misaridis, Athanasios

    Modulated (or coded) excitation signals can potentially improve the quality and increase the frame rate in medical ultrasound scanners. The aim of this dissertation is to investigate systematically the applicability of modulated signals in medical ultrasound imaging and to suggest appropriate...... of the excitation signal. Although a gain in signal-to-noise ratio of about 20 dB is theoretically possible for the time-bandwidth product available in ultrasound, it is shown that the effects of transducer weighting and tissue attenuation reduce the maximum gain at 10 dB for robust compression with low sidelobes...... is described. Application of coded excitation in array imaging is evaluated through simulations in Field II. The low degree of the orthogonality among coded signals for ultrasound systems is first discussed, and the effect of mismatched filtering in the cross-correlation properties of the signals is evaluated...

  16. Copper (II)

    African Journals Online (AJOL)

    CLEMENT O BEWAJI

    ABSTRACT: A Schiff base was prepared from the reaction of 2 - amino - 3 – methylbutanoic acid and 2, 4 - pentanedione. The reaction of the prepared Schiff base with ethanolic solution of copper (II) chloride formed diaquo bis( N – 2 – amino – 3 - methylbutyl - 2, 4 - pentanedionato) copper (II) complex. The Schiff base is ...

  17. LCA and Sustainability

    DEFF Research Database (Denmark)

    Moltesen, Andreas; Bjørn, Anders

    2017-01-01

    LCA is often presented as a sustainability assessment tool. This chapter analyses the relationship between LCA and sustainability. This is done by first outlining the history of the sustainability concept, which gained momentum with the Brundtland Commission’s report ‘Our Common Future report...... is then demonstrated, and the strategy of LCA to achieving environmental protection, namely to guide the reduction of environmental impacts per delivery of a function, is explained. The attempt to broaden the scope of LCA, beyond environmental protection, by so-called life cycle sustainability assessment (LCSA......) is outlined. Finally, the limitations of LCA in guiding a sustainable development are discussed....

  18. From sustainable buildings to sustainable business

    OpenAIRE

    Mia Andelin

    2012-01-01

    The United Nations Environment Program (UNEP) Sustainable Buildings & Climate Initiative reports that buildings are responsible for more than 40 percent of global energy use and over one third of global greenhouse gas (GHG) emissions. The construction and real estate sector has the potential to play a significant role in the response to climate change. During the latest years the increase in attention to sustainability and green building by planners, developers, and investors has been remarka...

  19. Sustainability Assessment of Higher Education Institutions in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Habib M. Alshuwaikhat

    2016-08-01

    Full Text Available Universities are paramount change drivers in bringing about a culture of sustainability in society by setting themselves up as models and nurseries for sustainable development. Thus, assessment of sustainability integration within universities is key to their impact on sustainable development. This study conducted an assessment of different public sector universities of Saudi Arabia based on five components: (i Teaching and Curriculum; (ii Research and Scholarship; (iii Campus Operations; (iv Management and Community; and (v Financial Management. The sustainability assessment questionnaire (SAQ was utilized as a tool to discern the component-wise sustainability assessment for Saudi universities. The outcomes of the survey reveal that, in stark contrast with the universities of the developed world, offerings of sustainability relevant academic courses in Saudi Arabia are still lacking. Most Saudi universities still need to integrate research and scholarship in the area of sustainability; sustainable-campus operations in the current scenario are not sufficient. The results also reveal that sustainability-related projects are not prioritized within universities and sustainable financial management practices are not significant. This article concludes by proposing some recommendations emphasizing the importance of adopting sustainability practices in Saudi universities.

  20. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    to renew itself without eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming...... to provide local citizens with a greater say in the future of urban sustainability research, this book shows how action research can make important methodological contributions to processes of social learning between citizens and scientists by enabling free spaces in peoples everyday life and within academia......How can action research further new research orientations towards sustainability? This book, empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating on urban sustainability, answers this question...

  1. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    to provide local citizens with a greater say in the future of urban sustainability research, this book shows how action research can make important methodological contributions to processes of social learning between citizens and scientists by enabling free spaces in peoples everyday life and within academia...... to renew itself without eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming......How can action research further new research orientations towards sustainability? This book, empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating on urban sustainability, answers this question...

  2. Sustainability in Business

    DEFF Research Database (Denmark)

    Tollin, Karin; Vej, Jesper

    2012-01-01

    How do companies integrate sustainability into their strategy and practices, and what factors explain their approach? In this paper a typology of sustainability strategies is presented as well as a conceptual framework relating sustainability at the company level to the functional level...... of marketing. The central contribution of the typology is a strategic and managerial view on sustainability. Furthermore, the typology shows that sustainability in business is enacted from different areas of competences and fields in the literature (e.g. supply chain management, corporate branding, value...... creation, product innovation and business model innovation). The empirical basis for the typology is an exploratory study of managers' mindsets about sustainability as strategy. Ten top managers involved with integrating sustainability within their companies have been interviewed. In order to reveal...

  3. Fur and Sustainability

    DEFF Research Database (Denmark)

    Skjold, Else; Csaba, Fabian

    2016-01-01

    This paper explores the notion of deeper luxury, which insists that 'real' luxury should involve sustainable practices in the production and consumption of luxury goods. It traces historical and recent developments in the field of fur, to understand the implications, uncertainties and ambiguities...... of luxury’s confrontation with sustainability. Considering fur in relation to future standards for luxury products, we raise questions about moral problematisation and justification of luxury in terms of sustainability. We first examine the encounter of luxury with sustainability and explain...... the significance of the notion of ‘deeper luxury’. After taking stock of the impact of sustainability on luxury and various directions in which sustainable luxury is evolving, we discuss concepts of sustainable development in relation to the history of moral problematisation of luxury. This leads to the case...

  4. Health and sustainability.

    Science.gov (United States)

    Kjӕrgård, Bente; Land, Birgit; Bransholm Pedersen, Kirsten

    2014-09-01

    In the present article, we explore how sustainable development strategies and health promotion strategies can be bridged. The concept of the 'duality of structure' is taken as our starting point for understanding the linkages between health promotion and sustainable development, and for uncovering the structural properties or conditions which either enable or constrain sustainable public health initiatives. We argue that strategies towards health promotion are not sufficiently integrated with strategies for sustainable development, and thus political strategies aimed at solving health problems or sustainability problems may cause new, undesired and unforeseen environmental or health problems. First, we explore how the relation between health and sustainability is articulated in international policy documents. Next, we develop a model for understanding the relation between health promotion and sustainability. Third, we use examples from agriculture and food production to illustrate that health and sustainability are mutually enabling and constraining. We conclude that while the renewed focus on food security and food inequalities has brought the health and sustainability dimensions of the food system onto the political agenda, the conceptualization of duality between health and sustainability could be a new platform for a critical and theoretical stance towards the market-oriented food system strategy. Thinking along the lines of duality means that the integration of health promotion strategies and sustainable development strategies cannot be based on an approach to integration in which either health or sustainability is given precedence over the other. From a duality perspective, integration means conceiving sustainability from a health perspective and health from a sustainability perspective. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Satiety signals and obesity.

    Science.gov (United States)

    Hellström, Per M

    2013-03-01

    The obesity epidemic over the world has called to attention different ways to manage this development. As bariatric surgery today is the only manner by which rapid and sustained weight control can be achieved, new ways of treating obesity are under investigation. This review focuses on today's knowledge on satiety signaling as a means to combat obesity. The combined knowledge achieved from obesity surgery with gastric bypass and duodenal switch together with the pharmacological treatment of type 2 diabetes have given us some clues of how to manage obesity. The basis for our understanding is the present research focusing on the gut peptide hormones that are released in response to food intake, and the paucity of satiety signaling seems to prevail in obesity. This means that obese patients experience less activation of higher brain centers in association with a meal and therefore compensate with increased meal size or frequent food intake. Altered satiety signaling primarily emanating from the gastrointestinal tract seems to lead to the development of obesity and type 2 diabetes. Pharmacological tools that enhance the gut hormone signaling are in focus for the upcoming venues of treatment.

  6. [What is sustainability science?].

    Science.gov (United States)

    Wu, Jian-Guo; Guo, Xiao-Chuan; Yang, Jie; Qian, Gui-Xia; Niu, Jian-Ming; Liang, Cun-Zhu; Zhang, Qing; Li, Ang

    2014-01-01

    Sustainability is the theme of our time and also the grandest challenge to humanity. Since the 1970s, the term, sustainable development, has frequently appeared in the scientific literature, governmental documents, media promotions for public goods, and commercial advertisements. However, the science that provides the theoretical foundation and practical guidance for sustainable development--sustainability science--only began to emerge in the beginning of the 21st century. Nevertheless, the field has rapidly developed in depth and expanded in scope during the past decade, with its core concepts and research methods coalescing. China, as the most populous country in the world and home to the philosophical root of sustainability science-the unity of man and nature, is obligated to take upon the challenge of our time, to facilitate global sustainability while pursuing the Chinese Dream, and to play a leading role in the development of sustainability science. Toward this grandiose goal, this paper presents the first Chinese introduction to sustainability science, which discusses its basic concepts, research questions, and future directions. Sustainability science is the study of the dynamic relationship between humans and the environment, particularly focusing on the vulnerability, robustness, resilience, and stability of the coupled human-environment system. It is a transdisciplinary science that integrates natural sciences with humanities and social sciences. It hinges on the environment-economy-society nexus, and merges basic and applied research. The key components of sustainability often change with time, place, and culture, and thus sustainability science needs to emphasize multi-scale studies in space and time, with emphasis on landscapes and regions over a horizon of 50 to 100 years. It needs to focus on the relationship between ecosystem services and human well-being, as influenced by biodiversity and ecosystem processes as well as climate change, land use

  7. decolonising sustainability: subverting and appropriating

    African Journals Online (AJOL)

    magnitude for environmental education. We can speak of sustainable development, sustainable economies, sustainable democracy, a sustainable world order, and sustainable modes of health maintenance, but when we turn to spiritual matters we are faced with the black hole of green· politics: what constitutes sustainable.

  8. SMART SUSTAINABLE ISLANDS VS SMART SUSTAINABLE CITIES

    Directory of Open Access Journals (Sweden)

    D. N. Pantazis

    2017-09-01

    Full Text Available This paper has several aims: a the presentation of a critical analysis of the terms “smart sustainable cities” and “smart sustainable islands” b the presentation of a number of principles towards to the development methodological framework of concepts and actions, in a form of a manual and actions guide, for the smartification and sustainability of islands. This kind of master plan is divided in thematic sectors (key factors which concern the insular municipalities c the creation of an island’s smartification and sustainability index d the first steps towards the creation of a portal for the presentation of our smartification actions manual, together with relative resources, smart applications examples, and, in the near future the first results of our index application in a number of Greek islands and e the presentation of some proposals of possible actions towards their sustainable development and smartification for the municipalities - islands of Paros and Antiparos in Greece, as case studies.

  9. Touchscreen Sustained Attention Task (SAT) for Rats.

    Science.gov (United States)

    Bangasser, Debra A; Wicks, Brittany; Waxler, David E; Eck, Samantha R

    2017-09-15

    Sustained attention is the ability to monitor intermittent and unpredictable events over a prolonged period of time. This attentional process subserves other aspects of cognition and is disrupted in certain neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Thus, it is clinically important to identify mechanisms that impair and improve sustained attention. Such mechanisms are often first discovered using rodent models. Therefore, several behavior procedures for testing aspects of sustained attention have been developed for rodents. One, first described by McGaughy and Sarter (1995), called the sustained attention task (SAT), trains rats to distinguish between signal (i.e., brief light presentation) and non-signal trials. The signals are short and thus require careful attention to be perceived. Attentional demands can be increased further by introducing a distractor (e.g., flashing houselight). We have modified this task for touchscreen operant chambers, which are configured with a touchscreen on one wall that can present stimuli and record responses. Here we detail our protocol for SAT in touchscreen chambers. Additionally, we present standard measures of performance in male and female Sprague-Dawley rats. Comparable performance on this task in both sexes highlights its use for attention studies, especially as more researchers are including female rodents in their experimental design. Moreover, the easy implementation of SAT for the increasingly popular touchscreen chambers increases its utility.

  10. Sustainable Building Operation

    DEFF Research Database (Denmark)

    Jensen, Jesper Ole

    2009-01-01

    Energy-savings in the existing building stock have becomes a main goal in national and international policies. Often focus is on building-renovations, whereas the potential of sustainable building operation to a large extent has been neglected. Nevertheless, international research as well...... as practical experiences from Danish housing estates indicates that there are large potentials for energy savings by focusing on the operation of the buildings. We suggest that in order to achieve sustainability in the existing housing, renovation and operations should be seen as integrated parts...... and that sustainable building operation can pave the way for sustainable building renovation. This paper discusses the use of sustainability building operation in Danish housing estates: Which tools, methods and technologies is being used, where are the barriers and where are the potentials? We define sustainable...

  11. Health and Sustainability

    DEFF Research Database (Denmark)

    Land, Birgit; Pedersen, Kirsten Bransholm; Kjærgård, Bente

    2014-01-01

    In the present article, we explore how sustainable development strategies and health promotion strategies can be bridged. The concept of the ‘duality of structure’ is taken as our starting point for understanding the linkages between health promotion and sustainable development, and for uncovering...... the structural properties or conditions which either enable or constrain sustainable public health initiatives. We argue that strategies towards health promotion are not sufficiently integrated with strategies for sustainable development, and thus political strategies aimed at solving health problems...... or sustainability problems may cause new, undesired and unforeseen environmental or health problems. First, we explore how the relation between health and sustainability is articulated in international policy documents. Next, we develop a model for understanding the relation between health promotion...

  12. At Home with Sustainability

    DEFF Research Database (Denmark)

    Hale, Lara

    2018-01-01

    of default rules in subconscious decision-making, this research finds that, ultimately, awareness drives the demand necessary for the creation of sustainable consumption. Whereas direct appeal to individuals has a disappointing level of influence on sustainability choices, it is understood that green......-fuel-based energy. To act otherwise requires additional effort and is less likely. Motivated by a need to understand how defaults might bridge standards and sustainable consumption, I investigate how organizational processes potentially lead from standardized green default rules to individual awareness that can...... spread and facilitate sustainable consumption. This paper examines the Active House sustainable building demonstrations in Europe in order to understand how (1) communications and market creation and (2) responsible, user-centered experimentation are organized to move from defaults to sustainable...

  13. ICT innovations for sustainability

    CERN Document Server

    Aebischer, Bernard

    2015-01-01

    ICT Innovations for Sustainability is an investigation of how information and communication technology can contribute to sustainable development. It presents clear definitions of sustainability, suggesting conceptual frameworks for the positive and negative effects of ICT on sustainable development. It reviews methods of assessing the direct and indirect impact of ICT systems on energy and materials demand, and examines the results of such assessments. In addition, it investigates ICT-based approaches to supporting sustainable patterns of production and consumption, analyzing them at various levels of abstraction – from end-user devices, Internet infrastructure, user behavior, and social practices to macro-economic indicators.   Combining approaches from Computer Science, Information Systems, Human-Computer Interaction, Economics, and Environmental Sciences, the book presents a new, holistic perspective on ICT for Sustainability (ICT4S). It is an indispensable resource for anyone working in the area of ICT...

  14. Sustainability and substitutability.

    Science.gov (United States)

    Fenichel, Eli P; Zhao, Jinhua

    2015-02-01

    Developing a quantitative science of sustainability requires bridging mathematical concepts from fields contributing to sustainability science. The concept of substitutability is central to sustainability but is defined differently by different fields. Specifically, economics tends to define substitutability as a marginal concept while fields such as ecology tend to focus on limiting behaviors. We explain how to reconcile these different views. We develop a model where investments can be made in knowledge to increase the elasticity of substitution. We explore the set of sustainable and optimal trajectories for natural capital extraction and built and knowledge capital accumulation. Investments in substitutability through knowledge stock accumulation affect the value of natural capital. Results suggest that investing in the knowledge stock, which can enhance substitutability, is critical to desirable sustainable outcomes. This result is robust even when natural capital is not managed optimally. This leads us to conclude that investments in the knowledge stock are of first order importance for sustainability.

  15. Sustainable Concrete Technology

    Directory of Open Access Journals (Sweden)

    Sim J.

    2015-12-01

    Full Text Available The growing concern over global warming and significant ecological changes requires sustainable development in all fields of science and technology. Concrete not only consumes huge amount of energy and natural sources, but also emits large amount of CO2, mainly due to the production of cement. It is evident that such large amount of concrete production has put significant impact on the energy, resource, environment, and ecology of the society. Hence, how to develop the concrete technology in a sustainable way has become a significant issue. In this paper, some of Korean researches for sustainable development of concrete are presented. These are sustainable strengthening for deteriorated concrete structure, sustainable reinforcement of new concrete structure, sustainable concrete using recycled aggregate and supplementary cementing materials and finally application of each technique to precast concrete.

  16. Sustainable fashion: New approaches

    OpenAIRE

    Niinimäki, Kirsi

    2013-01-01

    This publication is intended to be used as a source of inspiration for designers and companies, and all stakeholders whose interest lies in the area of sustainable fashion. While the strategies for sustainability are complex and approaches are many, this publication presents only a few ways to approach sustainable fashion. I hope the publication offers inspiration on how to make positive change in current practices and how to effect new mindsets, creating transformative fashion. Theoretica...

  17. Education for sustainable development

    DEFF Research Database (Denmark)

    Breiting, Søren

    2009-01-01

     An introduction to the idea of sustainable development (SD) and education for sustainable development (ESD) with reference to the international Decade for Education for Sustainable Development . The chapter includes a focus on conflicting interests between present and future generations related...... to the use of natural resources and other matters, and how that kind of issues can be dealt with in education as ESD....

  18. A highly sustainable house

    OpenAIRE

    Cordero, Raúl; Mercader-Moyano, Pilar (Coordinador)

    2017-01-01

    A sustainable house is capable of generating and self-sustaining energy by itself to function autonomously, that is to say, without depending on external supply networks. That is possible by supplying the internal energy consumption through renewable energy. This work describes and analyzes the construction of a sustainable house in Paute, Ecuador. The goal of this house was to achieve selfsustainability in several aspects such as construction techniques, creative and functi...

  19. Sustainability Assessment Circle

    OpenAIRE

    Schlör, H.; Hake, J.-Fr.

    2015-01-01

    Since the nineteen seventies, science and society have been discussing the worldwide ecological, economic, and social problems caused by industrialization and globalization. Sustainable development is perceived as a strategy for coping with these problems. The Rio +20 conference in 2012 confirmed the sustainability concept and introduced the green economy and the life cycle sustainable assessment as its implementation and operationalization strategy and tool.In the following, we will demonstr...

  20. Strategic Planning for Sustainability in Canadian Higher Education

    Directory of Open Access Journals (Sweden)

    Andrew Bieler

    2017-01-01

    Full Text Available This paper reviews representations of sustainability in the strategic plans of Canadian higher education institutions (HEIs. A content analysis of the strategic plans of 50 HEIs was undertaken to determine the extent to which sustainability is included as a significant policy priority in the plans, including across the five domains of governance, education, campus operations, research, and community outreach. We found 41 strategic plans with some discussion of sustainability, and identified three characteristic types of response: (i accommodative responses that include sustainability as one of many policy priorities and address only one or two sustainability domains; (ii reformative responses that involve some alignment of policy priorities with sustainability values in at least a few domains; and (iii progressive responses that make connections across four or five domains and offer a more detailed discussion of sustainability and sustainability-specific policies. Accommodative responses were dominant. More progressive responses were typically from institutions participating in the Sustainability Tracking, Assessment and Rating System (STARS of the Association for the Advancement of Sustainability in Higher Education. The paper concludes with consideration of the political and economic contexts contributing to this relative prevalence of accommodative responses to sustainability.

  1. Exercício de força ativa a via AKT/mTor pelo receptor de angiotensina II tipo I no músculo cardíaco de ratos Activation of AKT-mTor signaling pathways by angiotensin II receptor type 1 after a session of strength exercise in cardiac muscle of rats

    Directory of Open Access Journals (Sweden)

    Stéphano Freitas Soares Melo

    2011-09-01

    Full Text Available O receptor de angiotensina II tipo I (AT1 tem uma importante participação no desenvolvimento da hipertrofia cardíaca. Em um trabalho publicado anteriormente, por nosso grupo, demonstramos que o bloqueio do receptor AT1 durante o treinamento de força inibiu a hipertrofia cardíaca em ratos. Por isso, o objetivo deste trabalho foi estudar a participação do receptor AT1 na ativação de vias de sinalização intracelular relacionadas com o aumento da síntese de proteína em ratos submetidos a uma sessão de exercício de força. Para isso, realizamos um experimento com seis grupos de animais (n = 6; cada: controle (Con, exercitado e sacrificado cinco minutos após o exercício (Exe 5, exercitado e sacrificado 30 minutos após o exercício (Exe 30, controle tratado com losartan (Con Los, tratado com losartan, exercitado e sacrificado cinco minutos após o exercício (Exe 5 Los, tratado com losartan, exercitado e sacrificado 30 minutos após o exercício (Exe 30 Los. Os resultados mostram que no grupo Exe 5 e Exe 30 ocorreu um aumento de 63% (P The angiotensin II type I (AT1 receptor has an important participation in the development of cardiac hypertrophy. Previously, we have shown that AT1 receptor participates in the cardiac hypertrophy induced by resistance training in rats. Here, we studied the involvement of AT1 receptor in the activation of intracellular signaling pathways related to the concentric HC in rats submitted to a session of strength exercise. Male Wistar rats were divided into 6 groups (n= 6 each: control (Con; exercised and killed 5 minutes after exercise (Exe 5; exercised and killed 30 minutes after exercise (Exe 30; control treated with Losartan (Con Los; treated with Losartan, exercised and killed 5 minutes after the exercise (Exe Los 5; treated with Losartan, exercised and killed 30 minutes after training (Exe Los 30. The results show that phosphorylation activity of AKT in group Exe 5 and Exe 30 increased 63% (P < 0

  2. Sustainability assessment and complementarity

    Directory of Open Access Journals (Sweden)

    Hugo F. Alrøe

    2016-03-01

    Full Text Available Sustainability assessments bring together different perspectives that pertain to sustainability to produce overall assessments, and a wealth of approaches and tools have been developed in the past decades. However, two major problems remain. The problem of integration concerns the surplus of possibilities for integration; different tools produce different assessments. The problem of implementation concerns the barrier between assessment and transformation; assessments do not lead to the expected changes in practice. We aim to analyze issues of complementarity in sustainability assessment and transformation as a key to better handling the problems of integration and implementation. Based on a generalization of Niels Bohr's complementarity from quantum mechanics, we have identified two forms of complementarity in sustainability assessment, observer stance complementarity and value complementarity. Unlike many other problems of sustainability assessment, complementarity is of a fundamental character connected to the very conditions for observation. Therefore, complementarity cannot be overcome methodologically, only handled better or worse. Science is essential to the societal goal of sustainability, but these issues of complementarity impede the constructive role of science in the transition to more sustainable structures and practices in food systems. The agencies of sustainability assessment and transformation need to be acutely aware of the importance of different perspectives and values and the complementarities that may be connected to these differences. An improved understanding of complementarity can help to better recognize and handle issues of complementarity. These deliberations have relevance not only for sustainability assessment, but more generally for transdisciplinary research on wicked problems.

  3. Predicting Sustainable Work Behavior

    DEFF Research Database (Denmark)

    Hald, Kim Sundtoft

    2013-01-01

    . Employee characteristics and general attitudes towards safety and work condition are included in the extended model. A survey was handed out to 654 employees in Chinese factories. This research contributes by demonstrating how employee- characteristics and general attitudes towards safety and work...... condition influence their sustainable work behavior. A new definition of sustainable work behavior is proposed.......Sustainable work behavior is an important issue for operations managers – it has implications for most outcomes of OM. This research explores the antecedents of sustainable work behavior. It revisits and extends the sociotechnical model developed by Brown et al. (2000) on predicting safe behavior...

  4. Sustainability needs the geosciences

    Science.gov (United States)

    Grimm, Nancy; van der Pluijm, Ben

    2012-10-01

    Science, Innovation, and Partnerships for Sustainable Solutions: A National Academies Symposium; Washington, D. C., 16-18 May 2012 It is no longer disputed that humanity has drastically changed the face of the planet and its life-support systems. The sustainability challenge is to meet people's needs today and in the future while sustaining life-support systems. This grand challenge demands a new scientific approach: use-inspired, solution-driven research that consciously links scientific research to societal decision-making and action. Sustainability science may help fulfill that need if it can engage communities of expertise across a wide range of disciplines and sectors, including the geosciences.

  5. Sustainable wireless networks

    CERN Document Server

    Zheng, Zhongming; Xuemin

    2013-01-01

    This brief focuses on network planning and resource allocation by jointly considering cost and energy sustainability in wireless networks with sustainable energy. The characteristics of green energy and investigating existing energy-efficient green approaches for wireless networks with sustainable energy is covered in the first part of this brief. The book then addresses the random availability and capacity of the energy supply. The authors explore how to maximize the energy sustainability of the network and minimize the failure probability that the mesh access points (APs) could deplete their

  6. Sustainable Management of Food

    Science.gov (United States)

    To provide information to organizations to help them implement sustainable food management, including joining the Food Recovery Challenge. To provide education and information to communities and concerned citizens.

  7. Advancing Sustainable Catalysis with Magnetite Surface ...

    Science.gov (United States)

    This article surveys the recent developments in the synthesis, surface modification, and synthetic applications of magnetitenanoparticles. The emergence of iron(II,III) oxide (triiron tetraoxide or magnetite; Fe3O4, or FeO•Fe2O3) nanoparticles as a sustainable support in heterogeneous catalysis is highlighted. Use of an oxide of earth-abundant iron for various applications in catalysis and environmental remediation.

  8. Behavioral ecology, endocrinology and signal reliability of electric communication

    Science.gov (United States)

    Gavassa, Sat; Goldina, Anna; Silva, Ana C.; Stoddard, Philip K.

    2013-01-01

    Summary The balance between the costs and benefits of conspicuous animal communication signals ensures that signal expression relates to the quality of the bearer. Signal plasticity enables males to enhance conspicuous signals to impress mates and competitors and to reduce signal expression to lower energetic and predation-related signaling costs when competition is low. While signal plasticity may benefit the signaler, it can compromise the reliability of the information conveyed by the signals. In this paper we review the effect of signal plasticity on the reliability of the electrocommunication signal of the gymnotiform fish Brachyhypopomus gauderio. We (1) summarize the endocrine regulation of signal plasticity, (2) explore the regulation of signal plasticity in females, (3) examine the information conveyed by the signal, (4) show how that information changes when the signal changes, and (5) consider the energetic strategies used to sustain expensive signaling. The electric organ discharge (EOD) of B. gauderio changes in response to social environment on two time scales. Two hormone classes, melanocortins and androgens, underlie the short-term and long-term modulation of signal amplitude and duration observed during social interaction. Population density drives signal amplitude enhancement, unexpectedly improving the reliability with which the signal predicts the signaler's size. The signal's second phase elongation predicts androgen levels and male reproductive condition. Males sustain signal enhancement with dietary intake, but when food is limited, they ‘go for broke’ and put extra energy into electric signals. Cortisol diminishes EOD parameters, but energy-limited males offset cortisol effects by boosting androgen levels. While physiological constraints are sufficient to maintain signal amplitude reliability, phenotypic integration and signaling costs maintain reliability of signal duration, consistent with theory of honest signaling. PMID:23761465

  9. Gibberellin signaling.

    Science.gov (United States)

    Hartweck, Lynn M

    2008-12-01

    This review covers recent advances in gibberellin (GA) signaling. GA signaling is now understood to hinge on DELLA proteins. DELLAs negatively regulate GA response by activating the promoters of several genes including Xerico, which upregulates the abscisic acid pathway which is antagonistic to GA. DELLAs also promote transcription of the GA receptor, GIBBERELLIN INSENSITIVE DWARF 1 (GID1) and indirectly regulate GA biosynthesis genes enhancing GA responsiveness and feedback control. A structural analysis of GID1 provides a model for understanding GA signaling. GA binds within a pocket of GID1, changes GID1 conformation and increases the affinity of GID1 for DELLA proteins. GA/GID1/DELLA has increased affinity for an F-Box protein and DELLAs are subsequently degraded via the proteasome. Therefore, GA induces growth through degradation of the DELLAs. The binding of DELLA proteins to three of the PHYTOCHROME INTERACTING FACTOR (PIF) proteins integrates light and GA signaling pathways. This binding prevents PIFs 3, 4, and 5 from functioning as positive transcriptional regulators of growth in the dark. Since PIFs are degraded in light, these PIFs can only function in the combined absence of light and presence of GA. New analyses suggest that GA signaling evolved at the same time or just after the plant vascular system and before plants acquired the capacity for seed reproduction. An analysis of sequences cloned from Physcomitrella suggests that GID1 and DELLAs were the first to evolve but did not initially interact. The more recently diverging spike moss Selaginella has all the genes required for GA biosynthesis and signaling, but the role of GA response in Selaginella physiology remains a mystery.

  10. Sustaining Education for Sustainability in Turbulent Times

    Science.gov (United States)

    Smith, Gregory A.; Stevenson, Robert B.

    2017-01-01

    A study of two schools in northern Australia demonstrated the impact on Education for Sustainability (EfS) initiatives of a disruptive policy environment set in motion by neoliberal reforms focused on standards, accountability, and international competitiveness. In one of the schools, a culture characterized by trust and an emphasis on cultivating…

  11. Bioenergy for sustainable development: An African context

    Science.gov (United States)

    Mangoyana, Robert Blessing

    This paper assesses the sustainability concerns of bioenergy systems against the prevailing and potential long term conditions in Sub-Saharan Africa with a special attention on agricultural and forestry waste, and cultivated bioenergy sources. Existing knowledge and processes about bioenergy systems are brought into a “sustainability framework” to support debate and decisions about the implementation of bioenergy systems in the region. Bioenergy systems have been recommended based on the potential to (i) meet domestic energy demand and reduce fuel importation (ii) diversify rural economies and create employment (iii) reduce poverty, and (iv) provide net energy gains and positive environmental impacts. However, biofuels will compete with food crops for land, labour, capital and entrepreneurial skills. Moreover the environmental benefits of some feedstocks are questionable. These challenges are, however, surmountable. It is concluded that biomass energy production could be an effective way to achieve sustainable development for bioenergy pathways that (i) are less land intensive, (ii) have positive net energy gains and environmental benefits, and (iii) provide local socio-economic benefits. Feasibility evaluations which put these issues into perspective are vital for sustainable application of agricultural and forest based bioenergy systems in Sub-Saharan Africa. Such evaluations should consider the long run potential of biofuels accounting for demographic, economic and technological changes and the related implications.

  12. Sustainable Brand-Based Innovation

    DEFF Research Database (Denmark)

    Nedergaard, Nicky; Gyrd-Jones, Richard

    2013-01-01

    processes. The article applies the concept of design thinking to develop a framework for Sustainable Brand-based Innovation. It is suggested that traditional market-oriented strategies should be complemented with intuitive thinking and abductive reasoning as associated with the concept of design thinking......The role of the corporate brand as a strategic resource in orienting innovation projects has only been cursorily addressed in the literature. As innovation is a key driver of brand growth, this article discusses how corporate brands can contribute to both guiding and driving such innovation....... On the basis of this framework, a conceptual model is elaborated integrating the three key management imperatives of: (i) orienting innovation and investments around the brand (brand orientation); (ii) thinking on a human scale to generate unique customer insights (intuitive customer orientation); and (iii...

  13. Innovations for sustainable public transport

    DEFF Research Database (Denmark)

    Hrelja, Robert; Hansson, Lisa; Richardson, Tim

    The aim of the project has been to analyse institutional and planning conditions for public transport in the Scandinavian countries from a comparative perspective, looking at the county of Skåne (Sweden) and the municipalities of Aarhus (Denmark) and Trondheim (Norway). The report considers...... qualitative case- studies of public transport in Skåne, Aarhus, and Trondheim, and uses an empirical material consisting of written material and interviews. It concludes that: (i) new forms of coordination between organizations and policy areas are called for in a number of critical areas, if public transport...... is to contribute effectively to the development of an efficient and sustainable transport system (for example, forms for the coordination of public transport, land use, and infrastructure planning); (ii) public transport must not be seen as an end in itself, or as merely a technical transport system; (iii...

  14. Sustainability in Software Engineering

    NARCIS (Netherlands)

    Wolfram, N.J.E.; Lago, P.; Osborne, Francesco

    2017-01-01

    The intersection between software engineering research and issues related to sustainability and green IT has been the subject of increasing attention. In spite of that, we observe that sustainability is still not clearly defined, or understood, in the field of software engineering. This lack of

  15. Engineering Students' Sustainability Approaches

    Science.gov (United States)

    Haase, S.

    2014-01-01

    Sustainability issues are increasingly important in engineering work all over the world. This article explores systematic differences in self-assessed competencies, interests, importance, engagement and practices of newly enrolled engineering students in Denmark in relation to environmental and non-environmental sustainability issues. The…

  16. Education for Sustainable development

    African Journals Online (AJOL)

    The unit-based sustainability assessment tool (USAT) was administered at Masinde Muliro University of. Science and Technology (MMUST), Kenya, between January and March 2012. The assessment focused on establishing to what extent the University integrated sustainability concerns into its core functions of teaching ...

  17. Sustainable consumption and happiness

    NARCIS (Netherlands)

    R. Veenhoven (Ruut)

    2009-01-01

    textabstractOne of the reasons for promoting sustainable consumption is that it may give rise to greater happiness for a greater number, at least in the long run. In this paper I explore the strength of that moral account. I take stock of the assumed effects of sustainable consumption on happiness

  18. Thermodynamics and sustainable development

    NARCIS (Netherlands)

    Cornelissen, Rene

    1997-01-01

    It is the objective of this thesis to demonstrate exergy analysis as a powerful instrument to obtain sustainable development. An important aspect of sustainable development is the minimisation of irreversibilities caused by the use of non-renewables. In order to limit the scope of this thesis

  19. Implementing Sustainable Institutional Practices

    Science.gov (United States)

    Shepard, Joseph; Johnson, Lewis

    2009-01-01

    Recent research has found that few institutions of higher education implemented the necessary strategies to make their campuses sustainable (Thompson and Green 2005). Ironically, universities are the segment of society with the most access to the intellectual capital needed to provide sound sustainable practices and measurements. Having top…

  20. Sustainable Consumption and Happiness

    NARCIS (Netherlands)

    R. Veenhoven (Ruut)

    2004-01-01

    textabstractOne of the reasons for promoting sustainable consumption is that it may give rise to greater happiness for a greater number, at least in the long run. In this paper I explore the strength of that moral account. I take stock of the assumed effects of sustainable consumption on happiness

  1. Aesthetics of sustainable architecture

    NARCIS (Netherlands)

    Lee, S.; Hill, G.; Sauerbruch, M.; Hutton, L.; Knowles, R.; Bothwell, K.; Brennan, J.; Jauslin, D.; Holzheu, H.; AlSayyad, N.; Arboleda, G.; Bharne, V.; Røstvik, H.; Kuma, K.; Sunikka-Blank, M.; Glaser, M.; Pero, E.; Sjkonsberg, M.; Teuffel, P.; Mangone, G.; Finocchiaro, L.; Hestnes, A.; Briggs, D.; Frampton, K.; Lee, S.

    2011-01-01

    The purpose of this book is to reveal, explore and further the debate on the aesthetic potentials of sustainable architecture and its practice. This book opens a new area of scholarship and discourse in the design and production of sustainable architecture, one that is based in aesthetics. The

  2. Sustainability: Cultural Considerations

    Science.gov (United States)

    2006-04-10

    Action for Sustainable Change. New York: American Management Association, 1999. Fullan , Michael . Leadership & Sustainability: System Thinkers...institutional Army. iii ACKNOWLEGMENTS I thank my project advisors, Mr. Michael Cain, Director, US Army Environmental Policy Institute and Mr...U.S. Army Environmental Policy Institute. Interview by author, date, Arlington, VA. 30 Michaels , Ed. “The War for Talent.” Interview by

  3. Leading Sustainability in Schools

    Science.gov (United States)

    Carr, Katie

    2016-01-01

    What is the role of schools, and more specifically school leadership, in the transition to a sustainable future for humankind? What different forms of leadership are needed to enable this role? The challenges are huge and complex and for those of us engaged in promoting sustainability learning, it is clear that the issue has never been more…

  4. Sustainability at BPA 2012

    Energy Technology Data Exchange (ETDEWEB)

    None

    2012-12-01

    BPA’s Sustainability Action Plan is grounded in our commitment to environmental stewardship and Executive Order 13514 that calls on the federal agencies to “lead by example” by setting a 2020 greenhouse gas emissions target, increasing energy efficiency; reducing fleet petroleum consumption; conserving water; reducing waste; supporting sustainable communities; and leveraging federal purchasing power to promoting environmentally responsible products and technologies.

  5. Entrepreneurship, Innovation and Sustainability

    OpenAIRE

    Keijzers, G.; Wempe, J.F.D.B. (Johan)

    2008-01-01

    Today, only a limited number of entrepreneurs and managers are facing up to the relevance of sustainability issues and the ways in which these may affect their own businesses. Even fewer entrepreneurs and managers see sustainability as a potential source of profit. These are the findings resulting from research carried out by Nyenrode Business Universiteit among well over 500 entrepreneurs and managers.

  6. Entrepreneurship, Innovation and Sustainability

    NARCIS (Netherlands)

    Keijzers, G. (Gerard); Wempe, J.F.D.B. (Johan)

    2008-01-01

    Today, only a limited number of entrepreneurs and managers are facing up to the relevance of sustainability issues and the ways in which these may affect their own businesses. Even fewer entrepreneurs and managers see sustainability as a potential source of profit. These are the findings resulting

  7. Sustaining Urban Forests

    Science.gov (United States)

    John F. Dwyer; David J. Nowak; Mary Heather Noble

    2003-01-01

    The significance of the urban forest resource and the powerful forces for change in the urban environment make sustainability a critical issue in urban forest management. The diversity, connectedness, and dynamics of the urban forest establish the context for management that will determine the sustainability of forest structure, health, functions, and benefits. A...

  8. Role of reactive oxygen species in extracellular signal-regulated ...

    Indian Academy of Sciences (India)

    Keywords. 6-hydroxydopamine; mitogen activated protein kinase; Parkinson's disease; redox signalling. Abstract. A number of reports indicate the potential for redox signalling via extracellular signal-regulated protein kinases (ERK) during neuronal injury. We have previously found that sustained ERK activation contributes ...

  9. Sustainability and uncertainty

    DEFF Research Database (Denmark)

    Jensen, Karsten Klint

    2007-01-01

    The widely used concept of sustainability is seldom precisely defined, and its clarification involves making up one's mind about a range of difficult questions. One line of research (bottom-up) takes sustaining a system over time as its starting point and then infers prescriptions from...... this requirement. Another line (top-down) takes an economical interpretation of the Brundtland Commission's suggestion that the present generation's needsatisfaction should not compromise the need-satisfaction of future generations as its starting point. It then measures sustainability at the level of society...... a clarified ethical goal, disagreements can arise. At present we do not know what substitutions will be possible in the future. This uncertainty clearly affects the prescriptions that follow from the measure of sustainability. Consequently, decisions about how to make future agriculture sustainable...

  10. Sustainable nuclear energy dilemma

    Directory of Open Access Journals (Sweden)

    Afgan Naim H.

    2013-01-01

    Full Text Available Sustainable energy development implies the need for the emerging potential energy sources which are not producing adverse effect to the environment. In this respect nuclear energy has gained the complimentary favor to be considered as the potential energy source without degradation of the environment. The sustainability evaluation of the nuclear energy systems has required the special attention to the criteria for the assessment of nuclear energy system before we can make firm justification of the sustainability of nuclear energy systems. In order to demonstrate the sustainability assessment of nuclear energy system this exercise has been devoted to the potential options of nuclear energy development, namely: short term option, medium term option, long term option and classical thermal system option. Criteria with following indicators are introduced in this analysis: nuclear indicator, economic indicator, environment indicator, social indicator... The Sustainability Index is used as the merit for the priority assessment among options under consideration.

  11. System Innovation for Sustainability

    DEFF Research Database (Denmark)

    System Innovation for Sustainability 2 focuses on change towards sustainable personal mobility based on implemented cases analysed from a system perspective. It examines what changes can be made to help us reduce our need for mobility, or start to make use of more sustainable mobility systems...... in order to provide sustainable solutions to our current ‘lock-in’ problems. Three major problem areas are considered (the ‘three Cs’): carbon emissions (and the growing contribution of mobility to the climate change crisis), congestion, and casualties. And each strategy proposed addresses one or more...... such as governments, manufacturers and consumers to intervene in the complex system to promote sustainable mobility. It concludes with a reflection on problems, trends and action needed. The ‘System Innovation for Sustainability’ series is the fruit of the first major international research network on SCP...

  12. Sustainability Marketing Commitment

    DEFF Research Database (Denmark)

    Tollin, Karin; Bech Christensen, Lars

    2017-01-01

    Corporate sustainability is an important strategy and value orientation for marketing, but scarce research addresses the organizational drivers and barriers to including it in companies’ marketing strategies and processes. The purpose of this study is to determine levels of commitment to corporate...... sustainability in marketing, processes associated with sustainability marketing commitment, drivers of sustainability marketing at the functional level of marketing, and its organizational context. Using survey data from 269 managers in marketing, covering a broad range of industries in Sweden and Denmark, we...... took a structural modelling approach to examine construct relationships, mediation, and moderation effects. Overall, the findings show that marketing capabilities associated with the innovation of new products, services, and business models constitute a strong driver to leverage sustainability...

  13. Sustainable Housing Design

    DEFF Research Database (Denmark)

    Lauring, Gert Michael

    2016-01-01

    Sustainable Housing Design. Integrating technical and housing quality aspects of sustainable architecture in civil engineering education. Summary An integrated design approach to sustainable architecture is outlined that combines concerns for zero energy building, good indoor climate and adequate...... constructions, private and public outdoor space, housing, urban and architectural quality. The educational framework, curriculum and inte-grated design methods are preconditions for optimizing a design process where technical criteria, functional concerns and housing quality are addressed from the initial...... phases. The outcome shows that integrated design further solutions where sustainable urban forms of settlement can be highly energy efficient while also attractive from a user perspective. Key words: Sustainable architecture, integrated design, zero-energy-housing, dense urban living. 1. Introduction...

  14. Sustainable built environments

    CERN Document Server

    Haase, Dagmar

    2013-01-01

    Sustainable design is a collective process whereby the built environment achieves unprecedented levels of ecological balance through new and retrofit construction, with the goal of long-term viability and humanization of architecture. Focusing on the environmental context, sustainable design merges the natural, minimum resource conditioning solutions of the past (daylight, solar heat, and natural ventilation) with the innovative technologies of the present.  The desired result is an integrated “intelligent” system that supports individual control with expert negotiation for resource consciousness. International experts in the field address the fundamental questions of sustainable design and landscape management: How should the sustainability of landscapes and buildings be evaluated? Which targets have to be set and which thresholds should not be exceeded? What forms of planning and governance structures exist and to what extent do they further the goals of sustainability?  Gathering 30 peer-reviewed ent...

  15. Agroecology and Sustainable Agriculture

    Directory of Open Access Journals (Sweden)

    Fabio Caporali

    Full Text Available In the framework of the 16th National Meeting of the Italian Ecological Society (“Global Change, Ecological Diversity and Sustainability”, University of Tuscia, Viterbo, 19-22 September 2006, a symposium was devoted to “Agroecology and Sustainable Development”. A major goal of this symposium was to contribute to keeping the dialogue among the experts of the various disciplines alive. Sustainability of agriculture is a challenge for society world wide. Universities and society as a whole have a responsibility in re-examining current perception of nature, of the world and of human society in the light of natural resources depletion, increasing pollution and social inequalities. The urgency to address sustainability issues is increasingly being reflected in the manner in which institutions of higher education around the world are giving priority to the teaching, research and practice of sustainability. The University of Tuscia is involved in international initiatives concerning teaching and research in Agroecology and Sustainable Agriculture.

  16. Agroecology and Sustainable Agriculture

    Directory of Open Access Journals (Sweden)

    Fabio Caporali

    2011-02-01

    Full Text Available In the framework of the 16th National Meeting of the Italian Ecological Society (“Global Change, Ecological Diversity and Sustainability”, University of Tuscia, Viterbo, 19-22 September 2006, a symposium was devoted to “Agroecology and Sustainable Development”. A major goal of this symposium was to contribute to keeping the dialogue among the experts of the various disciplines alive. Sustainability of agriculture is a challenge for society world wide. Universities and society as a whole have a responsibility in re-examining current perception of nature, of the world and of human society in the light of natural resources depletion, increasing pollution and social inequalities. The urgency to address sustainability issues is increasingly being reflected in the manner in which institutions of higher education around the world are giving priority to the teaching, research and practice of sustainability. The University of Tuscia is involved in international initiatives concerning teaching and research in Agroecology and Sustainable Agriculture.

  17. The Role of miR-330-3p/PKC-α Signaling Pathway in Low-Dose Endothelial-Monocyte Activating Polypeptide-II Increasing the Permeability of Blood-Tumor Barrier

    Directory of Open Access Journals (Sweden)

    Jiahui Liu

    2017-12-01

    Full Text Available This study was performed to determine whether EMAP II increases the permeability of the blood-tumor barrier (BTB by affecting the expression of miR-330-3p as well as its possible mechanisms. We determined the over-expression of miR-330-3p in glioma microvascular endothelial cells (GECs by Real-time PCR. Endothelial monocyte-activating polypeptide-II (EMAP-II significantly decreased the expression of miR-330-3p in GECs. Pre-miR-330-3p markedly decreased the permeability of BTB and increased the expression of tight junction (TJ related proteins ZO-1, occludin and claudin-5, however, anti-miR-330-3p had the opposite effects. Anti-miR-330-3p could enhance the effect of EMAP-II on increasing the permeability of BTB, however, pre-miR-330-3p partly reversed the effect of EMAP-II on that. Similarly, anti-miR-330-3p improved the effects of EMAP-II on increasing the expression levels of PKC-α and p-PKC-α in GECs and pre-miR-330-3p partly reversed the effects. MiR-330-3p could target bind to the 3′UTR of PKC-α. The results of in vivo experiments were similar to those of in vitro experiments. These suggested that EMAP-II could increase the permeability of BTB through inhibiting miR-330-3p which target negative regulation of PKC-α. Pre-miR-330-3p and PKC-α inhibitor decreased the BTB permeability and up-regulated the expression levels of ZO-1, occludin and claudin-5 while anti-miR-330-3p and PKC-α activator brought the reverse effects. Compared with EMAP-II, anti-miR-330-3p and PKC-α activator alone, the combination of the three combinations significantly increased the BTB permeability. EMAP-II combined with anti-miR-330-3p and PKCα activator could enhance the DOX’s effects on inhibiting the cell viabilities and increasing the apoptosis of U87 glioma cells. Our studies suggest that low-dose EMAP-II up-regulates the expression of PKC-α and increases the activity of PKC-α by inhibiting the expression of miR-330-3p, reduces the expression of ZO-1

  18. Problem Based Learning and sustainability

    DEFF Research Database (Denmark)

    Pizzol, Massimo; Løkke, Søren; Schmidt, Jannick Højrup

    Problem-Based Learning (PBL) is a style of active learning based on problem solving. PBL aims at providing university students with flexible knowledge, capacity to self-learning, and skills in problem solving and collaboration. In this context, the present study explores the advantages and challe......Problem-Based Learning (PBL) is a style of active learning based on problem solving. PBL aims at providing university students with flexible knowledge, capacity to self-learning, and skills in problem solving and collaboration. In this context, the present study explores the advantages...... and challenges that the PBL model offers for developing five key competences in sustainability: (i) system thinking, (ii) interpersonal competence, (iii) anticipatory competence, (iv) strategic competence, (v) normative competences. The study draws on the experiences from PBL activities performed at Aalborg...... University (AAU), Denmark, and focuses on the teaching of Life Cycle Assessment as a method for sustainability assessment. The objective is providing recommendations for future LCA teaching and learning. PBL activites performed at AAU were evaluated critically to detemine to what extent they addressed...

  19. Ni(II), Mn(II), Zn(II)

    Indian Academy of Sciences (India)

    Unknown

    Abstract. Neutral tetradentate N2O2 type complexes of Cu(II), Ni(II), Mn(II),. Zn(II) and VO(II) have been synthesised using a Schiff base formed by the condensation of o-phenylenediamine with acetoacetanilide in alcohol medium. All the complexes were characterised on the basis of their microanalytical data, molar.

  20. Agent-based modeling of sustainable behaviors

    CERN Document Server

    Sánchez-Maroño, Noelia; Fontenla-Romero, Oscar; Polhill, J; Craig, Tony; Bajo, Javier; Corchado, Juan

    2017-01-01

    Using the O.D.D. (Overview, Design concepts, Detail) protocol, this title explores the role of agent-based modeling in predicting the feasibility of various approaches to sustainability. The chapters incorporated in this volume consist of real case studies to illustrate the utility of agent-based modeling and complexity theory in discovering a path to more efficient and sustainable lifestyles. The topics covered within include: households' attitudes toward recycling, designing decision trees for representing sustainable behaviors, negotiation-based parking allocation, auction-based traffic signal control, and others. This selection of papers will be of interest to social scientists who wish to learn more about agent-based modeling as well as experts in the field of agent-based modeling.

  1. Pb II

    African Journals Online (AJOL)

    Windows User

    used was oven-dried till constant weight and were ground to fine powder in a pestle and mortar. RESULTS AND DISCUSSION. Screening for lead sorption. 15 fungal isolates were screened for Pb(II) biosorption potential at initial pH value of 4.5 and temperature 30°C by incubating freshly harvested wet biomass corres-.

  2. Sustainable winegrowing: current perspectives

    Directory of Open Access Journals (Sweden)

    Mariani A

    2015-05-01

    Full Text Available Angela Mariani,1 Antonella Vastola2 1Department of Economic and Legal Studies, University Parthenope, Naples, 2School of Agricultural, Forestry, Food and Environmental Sciences, University of Basilicata, Potenza, Italy Abstract: The winegrowing sector worldwide is strongly committed to improving environmental and social sustainability. The aim of this work, based on a literature review, is to highlight current sustainability perspectives and the related main issues. There is a broad consensus that the challenge to achieve a greater spread of sustainable practices is to enhance environmental and social sustainability while maintaining economic viability. From the producers' point of view, the priority is to bridge the still substantial knowledge gaps in terms of perceived environmental benefits, economic benefits, and costs. Thus, an increased research effort focusing on the costs and benefits of different winegrowing practices and technical assistance with implementation might support their diffusion. Moreover, targeted marketing strategies are needed to: enhance consumers' involvement and their attitude toward sustainable wine; improve understanding and use of sustainable labels and claims; and raise awareness of some environmental credentials of wine packaging, mainly with reference to lightweight glass bottles. Keywords: winegrower, sustainability, wine, consumer, marketing strategies

  3. Sustainability Infused Curriculum

    Science.gov (United States)

    Ibarra, D. L.

    2015-12-01

    The Independent Schools Foundation Academy (ISF) in Hong Kong established a sustainability policy in 2015, which explicitly states, "an experimentally integrated, environmentally and ethically sustainable system of science education and conservation practices based on the 2012 Jeju Declaration of the World Conservation Congress will be implemented through the school". ISF Academy is a private Chinese bilingual school in Hong Kong serving over 1500 students K-12, following the framework and curriculum of the International Baccalaureate Organization (IBO). The strategy behind the implementation of this policy includes: development of a scientific sustainable curriculum that is age appropriate; establish a culture of sustainability within the ISF community and beyond to the wider HK community; install sustainable infrastructure that allows students to learn; and learn first hand sustainable living practices. It is well understood that solutions to the environmental challenges facing Hong Kong and our planet will require multiple disciplines. The current sustainability programs at ISF include: a) a whole school aerobic food waste composting system and organic farming, b) energy consumption monitoring of existing buildings, c) upcoming installation of an air pollution monitoring equipment that will correlate with the AQHI data collected by the Hong Kong government, d) a Renewable Energy Education Center (REEC) that will teach students about RE and also produce solar energy for classroom consumption, and e) student lead environmental group that manages the paper and used cooking oil recycling on campus. The Shuyuan Science and Sustainability faculty work closely with classroom teachers to ensure that the above mentioned projects are incorporated into the curriculum throughout the school. Interdisciplinary units (IDU) of study are being developed that encourage faculty and students to work across subject areas. Projects include Personal Projects, Extended Essays

  4. Making technological innovation work for sustainable development

    Science.gov (United States)

    Anadon, Laura Diaz; Harley, Alicia G.; Matus, Kira; Moon, Suerie; Murthy, Sharmila L.

    2016-01-01

    This paper presents insights and action proposals to better harness technological innovation for sustainable development. We begin with three key insights from scholarship and practice. First, technological innovation processes do not follow a set sequence but rather emerge from complex adaptive systems involving many actors and institutions operating simultaneously from local to global scales. Barriers arise at all stages of innovation, from the invention of a technology through its selection, production, adaptation, adoption, and retirement. Second, learning from past efforts to mobilize innovation for sustainable development can be greatly improved through structured cross-sectoral comparisons that recognize the socio-technical nature of innovation systems. Third, current institutions (rules, norms, and incentives) shaping technological innovation are often not aligned toward the goals of sustainable development because impoverished, marginalized, and unborn populations too often lack the economic and political power to shape innovation systems to meet their needs. However, these institutions can be reformed, and many actors have the power to do so through research, advocacy, training, convening, policymaking, and financing. We conclude with three practice-oriented recommendations to further realize the potential of innovation for sustainable development: (i) channels for regularized learning across domains of practice should be established; (ii) measures that systematically take into account the interests of underserved populations throughout the innovation process should be developed; and (iii) institutions should be reformed to reorient innovation systems toward sustainable development and ensure that all innovation stages and scales are considered at the outset. PMID:27519800

  5. Making technological innovation work for sustainable development.

    Science.gov (United States)

    Anadon, Laura Diaz; Chan, Gabriel; Harley, Alicia G; Matus, Kira; Moon, Suerie; Murthy, Sharmila L; Clark, William C

    2016-08-30

    This paper presents insights and action proposals to better harness technological innovation for sustainable development. We begin with three key insights from scholarship and practice. First, technological innovation processes do not follow a set sequence but rather emerge from complex adaptive systems involving many actors and institutions operating simultaneously from local to global scales. Barriers arise at all stages of innovation, from the invention of a technology through its selection, production, adaptation, adoption, and retirement. Second, learning from past efforts to mobilize innovation for sustainable development can be greatly improved through structured cross-sectoral comparisons that recognize the socio-technical nature of innovation systems. Third, current institutions (rules, norms, and incentives) shaping technological innovation are often not aligned toward the goals of sustainable development because impoverished, marginalized, and unborn populations too often lack the economic and political power to shape innovation systems to meet their needs. However, these institutions can be reformed, and many actors have the power to do so through research, advocacy, training, convening, policymaking, and financing. We conclude with three practice-oriented recommendations to further realize the potential of innovation for sustainable development: (i) channels for regularized learning across domains of practice should be established; (ii) measures that systematically take into account the interests of underserved populations throughout the innovation process should be developed; and (iii) institutions should be reformed to reorient innovation systems toward sustainable development and ensure that all innovation stages and scales are considered at the outset.

  6. Merlin inhibits Wnt/β-catenin signaling by blocking LRP6 phosphorylation.

    Science.gov (United States)

    Kim, M; Kim, S; Lee, S-H; Kim, W; Sohn, M-J; Kim, H-S; Kim, J; Jho, E-H

    2016-10-01

    Merlin, encoded by the NF2 gene, is a tumor suppressor that acts by inhibiting mitogenic signaling and is mutated in Neurofibromatosis type II (NF2) disease, although its molecular mechanism is not fully understood. Here, we observed that Merlin inhibited Wnt/β-catenin signaling by blocking phosphorylation of LRP6, which is necessary for Wnt signal transduction, whereas mutated Merlin in NF2 patients did not. Treatment with Wnt3a enhanced phosphorylation of Ser518 in Merlin via activation of PAK1 in a PIP2-dependent manner. Phosphorylated Merlin dissociated from LRP6, allowing for phosphorylation of LRP6. Tissues from NF2 patients exhibited higher levels of β-catenin, and proliferation of RT4-D6P2T rat schwannoma cells was significantly reduced by treatment with chemical inhibitors of Wnt/β-catenin signaling. Taken together, our findings suggest that sustained activation of Wnt/β-catenin signaling due to abrogation of Merlin-mediated inhibition of LRP6 phosphorylation may be a cause of NF2 disease.

  7. Textiles and clothing sustainability nanotextiles and sustainability

    CERN Document Server

    2017-01-01

    This book highlights the sustainability aspects of textiles and clothing sector in light of nanomaterials and technologies. The invasion of nano in every industrial sector has been important and has made remarkable changes as well as posed new challenges, including the textiles and clothing sector. There is quite a great deal of research happening in terms of nano materials for textiles across the globe, some of which are covered in this book. .

  8. Integrating Sustainability in Organisations: An Activity-Based Sustainability Model

    National Research Council Canada - National Science Library

    Ana Rodríguez-Olalla; Carmen Aviles-Palacios

    2017-01-01

    .... Although global integration models address sustainability in organisations, these models present shortcomings and limitations and do not describe how to achieve the integration of sustainability...

  9. Sustainable Entrepreneurial Orientation: A Business Strategic Approach for Sustainable Development

    National Research Council Canada - National Science Library

    Ana Criado-Gomis; Amparo Cervera-Taulet; Maria-Angeles Iniesta-Bonillo

    2017-01-01

    This paper proposes sustainable entrepreneurial orientation (SEO) as a multidimensional construct that offers researchers the possibility of empirically testing their theoretical proposals in the sustainable entrepreneurship field...

  10. Numeracy and sustainability

    Directory of Open Access Journals (Sweden)

    John Cairns Jr.

    2003-11-01

    Full Text Available Sustainable use of the planet is based on the assumption that humankind can maintain conditions suitable for inhabiting the planet indefinitely. No robust evidence supports this assumption nor rejects it, and adequate evidence on this issue may not be available for centuries. Numeracy is the ability to use or understand numerical techniques of mathematics. Even if adequate numerical data were available, the important decisions humankind makes regarding sustainable use of the planet should not be guided by numerical information alone, such as economic numbers, but by eco- and sustainability ethics, which provides a values framework that indicates how the numbers should be used and interpreted.

  11. Strategic corporate sustainability

    DEFF Research Database (Denmark)

    Grewatsch, Sylvia; Rohrbeck, René; Madsen, Henning

    This paper aims to advance the understanding of the circumstances under which corporate sustainability (CS) pays off. On the basis of a review of 129 major papers from both the sustainability and general management literature, we discuss the development of the research field. In addition we discuss...... antecedents and outcomes. To overcome this limitation we propose an integrated typology which may facilitate more research on the link between corporate sustainability performance (CSP) and corporate financial performance (CFP). Our expectation is that the strategy type might play a moderating or mediating...

  12. Sustainability in Materials Education

    Science.gov (United States)

    Fergus, Jeffrey W.; Twigge-Molecey, Christopher; Mcguffin-Cawley, James

    2013-08-01

    Consideration of the environmental and societal impacts of engineering products and processes is becoming increasingly important, so sustainability-related issues need to be addressed in educating engineers. Awareness of sustainability issues is particularly important for materials and metallurgical scientists and engineers because they are involved in both developing processes and selecting materials with low-energy use and low environmental impact. In this article, activities at TMS to identify sustainability-related educational needs and opportunities to address these needs will be discussed.

  13. Sustainable Facilities Management

    DEFF Research Database (Denmark)

    Nielsen, Susanne Balslev; Elle, Morten; Hoffmann, Birgitte

    2004-01-01

    The Danish public housing sector has more than 20 years of experience with sustainable facilities management based on user involvement. The paper outlines this development in a historical perspective and gives an analysis of different approaches to sustainable facilities management. The focus...... is on the housing departments and strateies for the management of the use of resources. The research methods used are case studies based on interviews in addition to literature studies. The paper explores lessons to be learned about sustainable facilities management in general, and points to a need for new...

  14. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    to provide local citizens with a greater say in the future of urban sustainability research, this book shows how action research can make important methodological contributions to processes of social learning between citizens and scientists by enabling free spaces in peoples everyday life and within academia......How can action research further new research orientations towards sustainability? This book, empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating on urban sustainability, answers this question...

  15. Sustaining Participatory Design Initiatives

    DEFF Research Database (Denmark)

    Iversen, Ole Sejer; Dindler, Christian

    2014-01-01

    While many participatory design (PD) projects succeed in establishing new organisational initiatives or creating technology that is attuned to the people affected, the issue of how such results are sustained after the project ends remains an important challenge. We explore the challenge...... these various forms of sustainability may be pursued in PD practice and how they can become a resource in reflecting on PD activities. Finally, we discuss implications for PD practice, suggesting that a nuanced conception of sustainability and how it may relate to PD practice are useful resources for designers...... and researchers before, during and after design processes. View full text Download full text...

  16. Sustainable Enterprise Excellence

    DEFF Research Database (Denmark)

    Edgeman, Rick; Williams, Joseph; Eskildsen, Jacob Kjær

    Sustainable Enterprise Excellence balances complementary and competing interests of key stakeholder segments, including society and the natural environment and increases the likelihood of superior and sustainable competitive positioning and hence long-term enterprise success that is defined...... by continuously relevant and responsible governance, strategy, actions and performance consistent with high-level organizational resilience, robustness and resplendence (R3). This is accomplished through organizational design and function emphasizing innovation, enterprise intelligence & analytics, operational......, supply chain, customer-related, human capital, financial, marketplace, societal, and environmental performance. Sustainable Enterprise Excellence integrates ethical, efficient and effective (E3) enterprise governance with 3E (equity, ecology, economy) Triple Top Line strategy throughout enterprise...

  17. Experience and Sustainable Consumption

    DEFF Research Database (Denmark)

    Rasmussen, Tove Arendt

    2014-01-01

    . Very often, however, the actual purchase does not live up to the demands of doing good in the sustainable consumption chain, and the individual might end up with a guilty conscience, which again is a possible trigger for lingering in a sentimental mode of guilt. Emotions of sentimentality may actually......Experience understood as experience-based consumption is by now fairly absent from the research agenda of the different theories on sustainable consumption. On the basis of Colin Campbell’s notion of romantic ethics and emotional sentimentality in modern hedonism, I claim that sustainable...

  18. Experience and Sustainable Consumption

    DEFF Research Database (Denmark)

    Rasmussen, Tove Arendt

    . Very often, however, the actual purchase does not live up to the demands of doing good in the sustainable consumption chain, and the individual might end up with a guilty conscience, which again is a possible trigger for lingering in a sentimental mode of guilt. Emotions of sentimentality may actually......Experience understood as experience-based consumption is by now fairly absent from the research agenda of the different theories on sustainable consumption. On the basis of Colin Campbell’s notion of romantic ethics and emotional sentimentality in modern hedonism, I claim that sustainable...

  19. Pre-paradigmatic Status of Industrial Sustainability: A Systematic Review

    OpenAIRE

    Smart, P; Hemel, S; Lettice, F; Adams, R; Evans, Stephen

    2017-01-01

    This paper seeks to progress Operations Management (OM) theory and practice by organising contributions to knowledge production, in Industrial Sustainability, from disparate researcher communities. It addresses the principal question ‘What scholarly dialogues can be explicated in the emerging research field of Industrial Sustainability?’ and sub-questions (i) what are the descriptive characteristics of the evidence base? and (ii) what thematic lines of scientific inquiry underpin the body of ...

  20. Sovereignty, individuality, and sustainability

    Directory of Open Access Journals (Sweden)

    John Cairns Jr.

    2003-09-01

    Full Text Available Humans must acknowledge that the biosphere is the essential support for all living organisms. In order to achieve sustainable use of the planet, humans must proceed beyond egocentrism, ethnocentrism, homocentrism, and biocentrism to ecocentrism. National states, with present policies, are a major obstacle to sustainable use of the planet. However, there is some evidence that the individual has increasing sovereignty at the expense of both nation states and the environment. Still, the primary obstacle to sustainability is inherent in the present system of sovereign nation states. The basic question is how much sovereignty must nation-states and individuals relinquish to preserve the health of Earth's biospheric life support system. A free and open exchange of thoughts on this subject is long overdue. To acheive sustainable use of the planet, humankind must view its identity within the context of the interdependent web of life.

  1. Sustainable Practices Innovation

    Science.gov (United States)

    Better sustainability means more environmentally conscious and efficient businesses and communities. EPA helps modify the way we consume energy, deal with waste, and grow our economy through programs such as Energy Star, E3, Smart Growth, and WaterSense.

  2. The Sustainable City.

    Science.gov (United States)

    Gangloff, Deborah

    1995-01-01

    Focuses on methods to make cities more sustainable through the processes of energy efficiency, pollution and waste reduction, capture of natural processes, and the merger of ecological, economic, and social factors. (LZ)

  3. Sustainable roadway lighting seminar.

    Science.gov (United States)

    2014-07-01

    The objective of this project was to develop and conduct a half-day educational seminar on sustainable : roadway lighting at three locations within New York State: Rochester, New York City, and Albany. : Primary attendees were engineers from the New ...

  4. Sustainable Enterprise Excellence

    DEFF Research Database (Denmark)

    Edgeman, Rick

    2013-01-01

    Structured Abstract Purpose: Sustainable Enterprise Excellence (SEE) is defined and developed through integration and expansion of business excellence modeling and sustainability thought. The intent is to enable simple yet reliable enterprise assessment of triple bottom line (TBL) performance...... and produce actionable enterprise foresight that can enable next best practices and sources of sustainable competitive advantage through innovation. Methodology: Key elements of SEE are identified from various business excellence and sustainability reporting sources, including the Global Reporting Initiative...... assessment approach similar in structure to those behind established excellence awards are developed that enable enterprise assessment of progress toward SEE. The resulting assessment is delivered in a highly consumable, combined narrative and graphic format referred to as a SEE NEWS Report. Practical...

  5. Strategic sustainability performance plan

    Science.gov (United States)

    2010-06-01

    In October 2009, President Obama signed Executive Order (EO) 13514 that sets sustainability : goals for Federal agencies and focuses on making improvements in environmental, energy and : economic performance. The Executive Order requires Federal agen...

  6. Transport, environment and sustainability

    DEFF Research Database (Denmark)

    Joumard, Robert; Gudmundsson, Henrik; Kehagia, Fotini

    2010-01-01

    This report is the final report of the action COST 356 'EST - Towards the definition of a measurable environmentally sustainable transport'. It tries to answer the following questions: How can environmental impacts of transport be measured? How can measurements be transformed into operational...... indicators? How can several indicators be jointly considered? And how can indicators be used in planning and decision making? Firstly we provide definition of 'indicator of environmental sustainability in transport'. The functions, strengths and weaknesses of indicators as measurement tools, and as decision...... support tools are discussed. We define what "environmental sustainability in transport" may mean through the transport system, the concepts of sustainable development and of environment. The concept of 'chain of causality' between a source and a final target is developed, as a common reference...

  7. Sustainability Principles in Practice

    DEFF Research Database (Denmark)

    Gani, Rafiqul; Wenzel, Henrik; Azapagic, Adisa

    2007-01-01

    generation, transport, heating and cooling, on the other hand, it has a considerable impact on the environment, via its resource consumption, its emissions and the impact of its products. New (sustainable) alternatives, for example, change of raw material base, use of renewable resources, efficient...... manufacture of chemical products and sustainable products and processes that can efficiently manufacture them, will need to be considered to meet the current and future challenges. Some of the important issues in this respect are how to generate/identify sustainable alternatives, how to analyze them, which...... criteria should be used to evaluate them, and how to implement them? The objective of this presentation is to highlight the use of systematic multidisciplinary approaches for generation of sustainable alternatives combined with methods/tools for analysis and evaluation. For generation of alternatives...

  8. Biorefinery Sustainability Analysis

    DEFF Research Database (Denmark)

    J. S. M. Silva, Carla; Prunescu, Remus Mihail; Gernaey, Krist

    2017-01-01

    This chapter deals with sustainability analysis of biorefinery systems in terms of environmental and socio-economic indicators . Life cycle analysis has methodological issues related to the functional unit (FU), allocation , land use and biogenic carbon neutrality of the reference system and of t......This chapter deals with sustainability analysis of biorefinery systems in terms of environmental and socio-economic indicators . Life cycle analysis has methodological issues related to the functional unit (FU), allocation , land use and biogenic carbon neutrality of the reference system...... and of the biorefinery-based system. Socio-economic criteria and indicators used in sustainability frameworks assessment are presented and discussed. There is not one single methodology that can aptly cover the synergies of environmental, economic, social and governance issues required to assess the sustainable...

  9. Social Health and Sustainability

    DEFF Research Database (Denmark)

    Andersen, Heidi Lene

    2015-01-01

    Abstract: This article discusses how to accomplish a transition towards healthy and sustainable futures. Despite political statements and profound theoretical developments, little has happened in the field of practice. This article presents a number of problematics in the theoretical and conceptual...... development within the fields of sustainability and health promotion. With this objective in mind, this article seeks to find solutions to a question raised by the WHO health and sustainability researcher, Illona Kickbusch: ‘What conceptual framing and common language can help move a shared agenda forward...... departments. The article demonstrates that an action research approach including an Aristotelean phronetic perspective can be successful in integrating health and sustainability in research, as well as in practice. There are two main conclusions from the empirical case study. The first is that the common...

  10. Crowdfunding for Sustainability

    DEFF Research Database (Denmark)

    Nielsen, Kristian Roed

    The dissertation sets out to explore the often ignored role of the consumer (end-user) within sustainable innovation by examining the potential of reward-based crowdfunding in enabling sustainable entrepreneurship. It explores under which conditions and to what extent rewardbased crowdfunding could...... benefit entrepreneurs with social and/or environmentally-oriented products. The dissertation employs four articles in order to explore this. The first sets the stage by systematically reviewing the various roles that end-users can adopt within sustainable innovation process. The second serves to present...... access, while paper four introduces the experimental evidence on the role of individual and product details in shaping pledging behavior as it relates to a diversity of (un)sustainable campaigns....

  11. Life Cycle Sustainability Dashboard

    DEFF Research Database (Denmark)

    Traverso, Marzia; Finkbeiner, Matthias; Jørgensen, Andreas

    2012-01-01

    One method to assess the sustainability performance of products is life cycle sustainability assessment (LCSA), which assesses product performance considering the environmental,economic, and social dimensions of the life cycle. The results of LCSA can be used to compare different products...... or to support decision making toward sustainable production and consumption. In both cases, LCSA results could be too disaggregated and consequently too difficult to understand and interpret by decision makers. As non-experts are usually the target audience of experts and scientists, and are also involved...... in decision-making processes, the necessity for a straightforward but comprehensive presentation of LCSA results is becoming strategically important. The implementation of the dashboard of sustainability proposed in this article offers a possible solution. An outstanding characteristic of the dashboard...

  12. Sustainable advanced construction technologies

    CSIR Research Space (South Africa)

    Kuchena, JC

    2009-11-01

    Full Text Available Advanced Construction Technologies (ACTs) are set to become the sustainable mainstay of the construction industry due to the demand for innovative housing solutions. Like most emerging economies, South Africa from a historical perspective and global...

  13. Sustainable Materials Management

    Science.gov (United States)

    To introduce businesses, NGOs, and government officials to the concept of Sustainable Materials Management (SMM). To provide tools to allow stakeholders to take a lifecycle approach managing their materials, & to encourage them to join a SMM challenge.

  14. Packaging for Sustainability

    CERN Document Server

    Lewis, Helen; Fitzpatrick, Leanne

    2012-01-01

    The packaging industry is under pressure from regulators, customers and other stakeholders to improve packaging’s sustainability by reducing its environmental and societal impacts. This is a considerable challenge because of the complex interactions between products and their packaging, and the many roles that packaging plays in the supply chain. Packaging for Sustainability is a concise and readable handbook for practitioners who are trying to implement sustainability strategies for packaging. Industry case studies are used throughout the book to illustrate possible applications and scenarios. Packaging for Sustainability draws on the expertise of researchers and industry practitioners to provide information on business benefits, environmental issues and priorities, environmental evaluation tools, design for environment, marketing strategies, and challenges for the future.

  15. The macroecology of sustainability

    Science.gov (United States)

    Burger, Joseph R.; Allen, Craig D.; Brown, James H.; Burnside, William R.; Davidson, Ana D.; Fristoe, Trevor S.; Hamilton, Marcus J.; Mercado-Silva, Norman; Nekola, Jeffrey C.; Okie, Jordan G.; Zuo, Wenyun

    2012-01-01

    The discipline of sustainability science has emerged in response to concerns of natural and social scientists, policymakers, and lay people about whether the Earth can continue to support human population growth and economic prosperity. Yet, sustainability science has developed largely independently from and with little reference to key ecological principles that govern life on Earth. A macroecological perspective highlights three principles that should be integral to sustainability science: 1) physical conservation laws govern the flows of energy and materials between human systems and the environment, 2) smaller systems are connected by these flows to larger systems in which they are embedded, and 3) global constraints ultimately limit flows at smaller scales. Over the past few decades, decreasing per capita rates of consumption of petroleum, phosphate, agricultural land, fresh water, fish, and wood indicate that the growing human population has surpassed the capacity of the Earth to supply enough of these essential resources to sustain even the current population and level of socioeconomic development.

  16. Food, Globalization and Sustainability

    NARCIS (Netherlands)

    Oosterveer, P.J.M.; Sonnenfeld, D.A.

    2011-01-01

    Food is increasingly traded internationally, thereby transforming the organisation of food production and consumption globally and influencing most food-related practices. This transition is generating unfamiliar challenges related to sustainability of food provision, the social impacts of

  17. The macroecology of sustainability.

    Science.gov (United States)

    Burger, Joseph R; Allen, Craig D; Brown, James H; Burnside, William R; Davidson, Ana D; Fristoe, Trevor S; Hamilton, Marcus J; Mercado-Silva, Norman; Nekola, Jeffrey C; Okie, Jordan G; Zuo, Wenyun

    2012-01-01

    The discipline of sustainability science has emerged in response to concerns of natural and social scientists, policymakers, and lay people about whether the Earth can continue to support human population growth and economic prosperity. Yet, sustainability science has developed largely independently from and with little reference to key ecological principles that govern life on Earth. A macroecological perspective highlights three principles that should be integral to sustainability science: 1) physical conservation laws govern the flows of energy and materials between human systems and the environment, 2) smaller systems are connected by these flows to larger systems in which they are embedded, and 3) global constraints ultimately limit flows at smaller scales. Over the past few decades, decreasing per capita rates of consumption of petroleum, phosphate, agricultural land, fresh water, fish, and wood indicate that the growing human population has surpassed the capacity of the Earth to supply enough of these essential resources to sustain even the current population and level of socioeconomic development.

  18. Sustainable investment: Literature overview

    NARCIS (Netherlands)

    Weda, J.; Kerste, M.; Rosenboom, N.

    2010-01-01

    Corporate Social Responsibility (CSR), or sustainability at the company level, entails incorporating ecological (environmental stakeholders) and social aspects (stakeholders other than shareholders and environmental stakeholders) when doing business. Socially Responsible Investment (SRI) concerns

  19. Regional Sustainable Environmental Management

    Science.gov (United States)

    Regional sustainable environmental management is an interdisciplinary effort to develop a sufficient understanding of the interactions between ecosystems, the economy, law, and technology to formulate effective long-term management strategies on a regional scale. Regional sustai...

  20. Towards Intelligently - Sustainable Cities?

    Directory of Open Access Journals (Sweden)

    Luca Salvati

    2013-04-01

    Full Text Available In the quest for achieving sustainable cities, Intelligent and Knowledge City Programmes (ICPs and KCPs represent cost-efficient strategies for improving the overall performance of urban systems. However, even though nobody argues on the desirability of making cities “smarter”, the fundamental questions of how and to what extent can ICPs and KCPs contribute to the achievement of urban sustainability lack a precise answer. In the attempt of providing a structured answer to these interrogatives, this paper presents a methodology developed for investigating the modalities through which ICPs and KCPs contribute to the achievement or urban sustainability. Results suggest that ICPs and KCPs efficacy lies in supporting cities achieve a sustainable urban metabolism through optimization, innovation and behavior changes.

  1. Sustaining Success in Haiti

    National Research Council Canada - National Science Library

    Oakley, Robert

    1996-01-01

    ... irreversible. The next several months are critical. Sustaining the success of Operation Uphold Democracy requires Haiti--and the international community--to confront, simultaneously, crucial transitions in political leadership, law and order, economic...

  2. Transgovernance: advancing sustainability governance

    National Research Council Canada - National Science Library

    Meuleman, Louis

    2013-01-01

    ... – together characterized as the emergence of a knowledge democracy – may imply for governance for sustainable development, on global and other levels of societal decision making, and the other way around...

  3. Commons, Sustainability, Democratization

    DEFF Research Database (Denmark)

    In nine chapters practical-conceptual drafts of action reserach in relation to sustainability are presented and examples of action research in Scandinavia, England, Nicaragua and Mozambique are described and analyzed....

  4. 2005 Environmental Sustainability Index (ESI)

    Data.gov (United States)

    National Aeronautics and Space Administration — The 2005 Environmental Sustainability Index (ESI) is a measure of overall progress towards environmental sustainability, developed for 146 countries. The index...

  5. Involving citizens in sustainable development

    DEFF Research Database (Denmark)

    Agger, Annika

    2010-01-01

    Local Environment The International Journal of Justice and Sustainability, Volume 15 Issue 6, 541......Local Environment The International Journal of Justice and Sustainability, Volume 15 Issue 6, 541...

  6. 2002 Environmental Sustainability Index (ESI)

    Data.gov (United States)

    National Aeronautics and Space Administration — The 2002 Environmental Sustainability Index (ESI) measures overall progress toward environmental sustainability for 142 countries based on environmental systems,...

  7. Genuine savings and sustainability

    OpenAIRE

    Hanley, Nicholas David; Dupuy, Louis Paul; MCLAUGHLIN, Eoin

    2015-01-01

    Genuine Savings has emerged as the leading economic indicator of sustainable economic development at the country level. It derives from the literatures on weak sustainability, wealth accounting and national income accounting. We discuss the theoretical underpinnings of GS, focusing on the relationship between changes in a nation's extended capital stock and the future path of consumption. The indicator has entered widespread use propelled by the World Bank's publications, despite its varying ...

  8. Leadership for Sustainable Installations

    Science.gov (United States)

    2011-04-01

    able_installations/. Accessed 15 April 2011) Leadership for Sustainable Installations By COL Charles Allen (Ret), U.S. Army War College The...number. 1. REPORT DATE APR 2011 2. REPORT TYPE 3. DATES COVERED 00-00-2011 to 00-00-2011 4. TITLE AND SUBTITLE Leadership for Sustainable...of the Army civilian workforce. During that decade, we followed the mandate of A-76 Commercial Sourcing and focused on developing the Most Efficient

  9. Settlement patterns and sustainability

    DEFF Research Database (Denmark)

    Hendriksen, Kåre

    This paper discusses settlement patterns and sustainability. Generally urbanization is recognised as an inevitable development driven by job opportunities, better service supply, education, and health services, and it is argued that this is the main driver for centralisation. Research based...... of utilization of local resources and trade opportunities. Furthermore the growing towns are struggling with an un-sustainable economic situation manly based on public financed jobs or welfare payments and with limited export oriented value creation....

  10. Innovating for sustainability

    DEFF Research Database (Denmark)

    The theme of the articles is innovating for sustainability. Empirically the articles shows how enterprises makes environmental innovations related to their processes and products within the organic dairy industry, the fish processing industry and the car industry.......The theme of the articles is innovating for sustainability. Empirically the articles shows how enterprises makes environmental innovations related to their processes and products within the organic dairy industry, the fish processing industry and the car industry....

  11. Agroecology and Sustainable Agriculture

    OpenAIRE

    Fabio Caporali

    2007-01-01

    In the framework of the 16th National Meeting of the Italian Ecological Society (“Global Change, Ecological Diversity and Sustainability”, University of Tuscia, Viterbo, 19-22 September 2006), a symposium was devoted to “Agroecology and Sustainable Development”. A major goal of this symposium was to contribute to keeping the dialogue among the experts of the various disciplines alive. Sustainability of agriculture is a challenge for society world wide. ...

  12. Assembling Sustainable Territories

    DEFF Research Database (Denmark)

    Vandergeest, Peter; Ponte, Stefano; Bush, Simon

    2015-01-01

    The authors show how certification assembles ‘sustainable’ territories through a complex layering of regulatory authority in which both government and nongovernment entities claim rule-making authority, sometimes working together, sometimes in parallel, sometimes competitively. It is argued...... dynamic in assembling sustainable territories, and that certification always involves state agencies in determining how the key elements that comprise it are defined. Whereas some state agencies have been suspicious of sustainability certification, others have embraced it or even used it to extend...

  13. Seeking sustainability leadership

    OpenAIRE

    Bendell, Jem; Little, Richard

    2015-01-01

    This paper critiques mainstream leadership and leadership development approaches to help inform the emerging field of sustainability leadership. Traditional leadership theory and education is argued to be highly problematic for the pursuit of sustainability leadership. A more critical approach is required, drawing upon insights from social theory, critical discourse analysis and psychology, which is attempted in this paper. Once deconstructed, leadership can be a useful framework for explorin...

  14. SUSTAINABLE TRAILER FLOORING

    OpenAIRE

    John Lu; Marc Chorney; Lowell Peterson

    2009-01-01

    Different trailer flooring materials, including wood-based, aluminum, steel, and synthetic plastic floors, were evaluated in accordance with their durability and sustainability to our natural environment. Wood-based trailer flooring is an eco-friendly product. It is the most sustainable trailer flooring material compared with fossil fuel-intensive steel, aluminum, and plastics. It is renewable and recyclable. Oak, hard maple, and apitong are strong and durable hardwood species that are curren...

  15. A sustainable economy

    OpenAIRE

    Pawlak, J. J.

    2008-01-01

    There exists a direct correlation between improvements in standard of living and the consumption of resources. To be able to maintain the standard of living of a modern developed country, society must adapt to an economy based on sustainable processes, energy, and raw materials. The sustainable economy presents itself as a disruptive technology to the traditional economy, which is based largely on non-renewable resources. The issue seems to be more about when will we switch to a sustainabl...

  16. Predicting sustainable work behavior

    OpenAIRE

    Sundtoft Hald, Kim

    2013-01-01

    Sustainable work behavior is an important issue for operations managers – it has implications for most outcomes of OM. This research explores the antecedents of sustainable work behavior. It revisits and extends the sociotechnical model developed by Brown et al. (2000) on predicting safe behavior. Employee characteristics and general attitudes towards safety and work condition are included in the extended model. A survey was handed out to 654 employees in Chinese factories. This research ...

  17. Sustainability of National Cohesion

    Directory of Open Access Journals (Sweden)

    Andrei Mihai Cristea

    2013-09-01

    Full Text Available In the European Union, cohesion policy is the third country after the domestic and social policy, as this policy is a tool for economic growth and also a balancing factor. Through its solidarity funds contribute to the other sectorial policies: the Common Agricultural Policy, social policy, environmental policy. This article aims to demonstrate the importance of cohesion policy in the national economy and how to improve its implementation by ensuring sustainable development and sustainable economic growth

  18. Sustainability, accounting and reporting

    CERN Document Server

    Balachandran, Kashi

    2011-01-01

    The topic of business sustainability is multidisciplinary in nature, and its complexity calls for putting in place a wide variety of research approaches, such as action research, case studies, surveys, model development etc. The papers presented in this ebook represent a comprehensive overview of recent advances in this area of accounting and reporting research. It contains six papers, covering how leasing can increase environmental benefits, CSR, developing social, environmental and economic indicators for SMEs, sustainability reporting and reputation risk and others.

  19. Sustainability of abrasive processes

    DEFF Research Database (Denmark)

    Aurich, J.C.; Linke, B.; Hauschild, Michael Zwicky

    2013-01-01

    This paper presents an overview of research on sustainability of abrasive processes. It incorporates results from a round robin study on ‘‘energy-efficiency of abrasive processes’’ which has been carried out within the scientific technical committee ‘‘abrasive processes’’ (STC G) of CIRP, the con......This paper presents an overview of research on sustainability of abrasive processes. It incorporates results from a round robin study on ‘‘energy-efficiency of abrasive processes’’ which has been carried out within the scientific technical committee ‘‘abrasive processes’’ (STC G) of CIRP......, the content of technical presentations in STC G, and the results of a comprehensive literature study. The approach to sustainability includes environmental, social, and economic sustainability in accordance with the definition proposed in the Brundtland Report of the United Nations [156]. The main focus...... is on environmental and social sustainability. Economic sustainability will be considered as manufacturing productivity. © 2013 CIRP....

  20. Sustainability at BPA 2013

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-12-01

    THIS IS THE THIRD YEAR BPA has reported on sustainability program accomplishments. The report provides an opportunity to review progress made on sustainability initiatives, evaluate how far we have come and how much we can improve. The program has demonstrated maturation as the concepts of sustainability and resource conservation are communicated and understood. The sustainability program started as an employee-driven “grass roots” effort in 2010. Sustainability is becoming a consideration in how work is performed. The establishment of several policies supporting sustainability efforts proves the positive progress being made. In 2009, BPA became a founder and member of The Climate Registry, a nonprofit collaboration that sets standards to calculate, verify and report greenhouse gas emissions. This year, BPA completed and published our Greenhouse Gas inventory for the years of 2009, 2010 and 2011. The 2012 inventory is currently in the process of third-party verification and scheduled for public release in January 2014. These inventories provide a concrete measure of the progress we are making.

  1. Sustainable Biofuels Development Center

    Energy Technology Data Exchange (ETDEWEB)

    Reardon, Kenneth F. [Colorado State Univ., Fort Collins, CO (United States)

    2015-03-01

    The mission of the Sustainable Bioenergy Development Center (SBDC) is to enhance the capability of America’s bioenergy industry to produce transportation fuels and chemical feedstocks on a large scale, with significant energy yields, at competitive cost, through sustainable production techniques. Research within the SBDC is organized in five areas: (1) Development of Sustainable Crops and Agricultural Strategies, (2) Improvement of Biomass Processing Technologies, (3) Biofuel Characterization and Engine Adaptation, (4) Production of Byproducts for Sustainable Biorefining, and (5) Sustainability Assessment, including evaluation of the ecosystem/climate change implication of center research and evaluation of the policy implications of widespread production and utilization of bioenergy. The overall goal of this project is to develop new sustainable bioenergy-related technologies. To achieve that goal, three specific activities were supported with DOE funds: bioenergy-related research initiation projects, bioenergy research and education via support of undergraduate and graduate students, and Research Support Activities (equipment purchases, travel to attend bioenergy conferences, and seminars). Numerous research findings in diverse fields related to bioenergy were produced from these activities and are summarized in this report.

  2. Social Sciences and Sustainability

    Directory of Open Access Journals (Sweden)

    Shu-Kun Lin

    2011-09-01

    Full Text Available At the time when the journal Sustainability [1] was launched, as a chemist and a scientist, I started to believe that social sciences may be more important to make humans sustainable. The broad journal title Social Sciences presents the opportunity for all social science scholars to have integrated consideration regarding the sustainability of humanity, because I am sure that science and technology alone cannot help. Science and technology may have in fact been contributing to accelerate the depletion of nonrenewable natural resources and putting human sustainability at risk since the industrial revolution about 150 years ago. I hope all intellectuals studying anthropology, archaeology, administration, communication, criminology, economics, education, government, linguistics, international relations, politics, sociology and, in some contexts, geography, history, law, and psychology publish with us to seek a solution to sustain humanity. Sustainability itself will also be a main topic of the journal Social Sciences. In addition to this integrated forum for social sciences, more topic specific journals, such as the already publishing Societies [2], will be launched. [...

  3. Sustainable Water Systems

    Directory of Open Access Journals (Sweden)

    Miklas Scholz

    2013-02-01

    Full Text Available Sustainable water systems often comprise complex combinations of traditional and new system components that mimic natural processes. These green systems aim to protect public health and safety, and restore natural and human landscapes. Green infrastructure elements such as most sustainable drainage systems trap storm water but may contaminate groundwater. There is a need to summarize recent trends in sustainable water systems management in a focused document. The aim of this special issue is therefore to disseminate and share scientific findings on novel sustainable water systems addressing recent problems and opportunities. This special issue focuses on the following key topics: climate change adaptation and vulnerability assessment of water resources systems; holistic water management; carbon credits; potable water savings; sustainable water technologies; nutrient management; holistic storm water reuse; water and wastewater infrastructure planning; ecological status of watercourses defined by the Water Framework Directive. The combined knowledge output advances the understanding of sustainable water, wastewater and storm water systems in the developed and developing world. The research highlights the need for integrated decision-support frameworks addressing the impact of climate change on local and national water resources management strategies involving all relevant stakeholders at all levels.

  4. Biofuels and sustainability.

    Science.gov (United States)

    Solomon, Barry D

    2010-01-01

    Interest in liquid biofuels production and use has increased worldwide as part of government policies to address the growing scarcity and riskiness of petroleum use, and, at least in theory, to help mitigate adverse global climate change. The existing biofuels markets are dominated by U.S. ethanol production based on cornstarch, Brazilian ethanol production based on sugarcane, and European biodiesel production based on rapeseed oil. Other promising efforts have included programs to shift toward the production and use of biofuels based on residues and waste materials from the agricultural and forestry sectors, and perennial grasses, such as switchgrass and miscanthus--so-called cellulosic ethanol. This article reviews these efforts and the recent literature in the context of ecological economics and sustainability science. Several common dimensions for sustainable biofuels are discussed: scale (resource assessment, land availability, and land use practices); efficiency (economic and energy); equity (geographic distribution of resources and the "food versus fuel" debate); socio-economic issues; and environmental effects and emissions. Recent proposals have been made for the development of sustainable biofuels criteria, culminating in standards released in Sweden in 2008 and a draft report from the international Roundtable on Sustainable Biofuels. These criteria hold promise for accelerating a shift away from unsustainable biofuels based on grain, such as corn, and toward possible sustainable feedstock and production practices that may be able to meet a variety of social, economic, and environmental sustainability criteria.

  5. Global sustainability: Toward definition

    Science.gov (United States)

    Brown, Becky J.; Hanson, Mark E.; Liverman, Diana M.; Merideth, Robert W.

    1987-11-01

    Sustainability is increasingly viewed as a desired goal of development and environmental management. This term has been used in numerous disciplines and in a variety of contexts, ranging from the concept of maximum sustainable yield in forestry and fisheries management to the vision of a sustainable society with a steady-state economy. The meaning of the term is strongly dependent on the context in which it is applied and on whether its use is based on a social, economic, or ecological perspective, Sustainability may be defined broadly or narrowly, but a useful definition must specify explicitly the context as well as the temporal and spatial scales being considered. Although societies differ in their conceptualizations of sustainability, indefinite human survival on a global scale requires certain basic support systems, which can be maintained only with a healthy environment and a stable human population. A clearer understanding of global sustainability and the development of appropriate indicators of the status of basic support systems would provide a useful framework for policy making.

  6. Human Capital and Sustainability

    Directory of Open Access Journals (Sweden)

    Garry Jacobs

    2011-01-01

    Full Text Available A study of sustainability needs to consider the role of all forms of capital—natural, biological, social, technological, financial, cultural—and the complex ways in which they interact. All forms of capital derive their value, utility and application from human mental awareness, creativity and social innovation. This makes human capital, including social capital, the central determinant of resource productivity and sustainability. Humanity has entered the Anthropocene Epoch in which human changes have become the predominant factor in evolution. Humanity is itself evolving from animal physicality to social vitality to mental individuality. This transition has profound bearing on human productive capabilities, adaptability, creativity and values, the organization of economy, public policy, social awareness and life styles that determine sustainability. This article examines the linkages between population, economic development, employment, education, health, social equity, cultural values, energy intensity and sustainability in the context of evolving human consciousness. It concludes that development of human capital is the critical determinant of long-term sustainability and that efforts to accelerate the evolution of human consciousness and emergence of mentally self-conscious individuals will be the most effective approach for ensuring a sustainable future. Education is the primary lever. Human choice matters.

  7. Manganese(II/II/II) and Manganese(III/II/III) Trinuclear Compounds. Structure and Solid and Solution Behavior.

    Science.gov (United States)

    Tangoulis, Vasilis; Malamatari, Dora A.; Soulti, Kali; Stergiou, Voula; Raptopoulou, Catherine P.; Terzis, Aris; Kabanos, Themistoklis A.; Kessissoglou, Dimitris P.

    1996-08-14

    Two mixed-valence Mn(III)Mn(II) complexes and a homo-valence Mn(II) trinuclear manganese complex of stoichiometry Mn(III)Mn(II)Mn(III)(5-Cl-Hsaladhp)(2)(AcO)(4)(MeOH)(2).4CH(3)OH (1a), Mn(III)Mn(II)Mn(III) (Hsaladhp)(2)(AcO)(2)(5-Cl-Sal)(2)(thf)(2) (3a) and Mn(II)Mn(II)Mn(II) (AcO)(6)(pybim)(2) (1b) where H(3)saladhp is a tridentate Schiff base ligand and pybim a neutral bidentate donor ligand, have been structurally characterized by using X-ray crystallography. The structurally characterized mixed-valence complexes have strictly 180 degrees Mn(III)-Mn(II)-Mn(III) angles as required by crystallographic inversion symmetry. The complexes are valence trapped with two terminal Mn(III) ions showing Jahn-Teller distortion along the acetate or salicylate-Mn(III)-X axis. The Mn.Mn separation is 3.511 Å and 3.507 Å respectively. The mixed-valence complexes have S = (3)/(2) ground state and the homovalence complex S = (5)/(2), with small antiferromagnetic exchange J couplings, -5.6 and -1.8 cm(-1), respectively, while the powder ESR spectra at 4 K show a broad low field signal with g approximately 4.3 for Mn(III)Mn(II)Mn(III) and a broad temperature-dependent signal at g = 2 for Mn(II)Mn(II)Mn(II). Crystal data for 1a: [C(36)H(60)O(20)N(2)Cl(2)Mn(3)], triclinic, space group P&onemacr;, a = 9.272(7) Å, b = 11.046(8) Å, c = 12.635(9) Å, alpha = 76.78(2) degrees, beta = 81.84(2) degrees, gamma = 85.90(2) degrees, Z = 1. Crystal data for 3a: [C(48)H(56)O(18)N(2)Cl(2)Mn(3)], monoclinic, space group P2(1)/n, a = 8.776(3) Å, b = 22.182(7) Å, c = 13.575(4) Å, beta = 94.44(1) degrees, Z = 2. Crystal data for 1b: [C(36)H(36)O(12)N(6)Mn(3)], triclinic, space group P&onemacr;, a = 13.345(6) Å, b = 8.514(4) Å, c = 9.494(4) Å, alpha = 75.48(1) degrees, beta = 75.83(1) degrees, gamma = 76.42(1) degrees, Z = 1.

  8. Angiotensin II and taste sensitivity

    Directory of Open Access Journals (Sweden)

    Noriatsu Shigemura, DDS, PhD

    2015-05-01

    Full Text Available The sense of taste plays a major role in evaluating the quality of food components in the oral cavity. Sweet, salty, umami, sour and bitter taste are generally accepted as five basic taste qualities. Among them, salty taste is attractive to animals and influences sodium intake. Angiotensin II (ANG II and aldosterone (ALDO, which is stimulated by ANG II are key hormones that regulate sodium homeostasis and water balance. At the peripheral gustatory organs, it has been reported that ALDO increases the amiloride-sensitivity of the rat gustatory neural responses to NaCl in a time course of several hours. A recent study demonstrated that ANG II suppresses amiloride-sensitivity of the mouse gustatory and behavioral responses to NaCl via its receptor AT1 within an hour. Moreover, ANG II enhances sweet taste sensitivity without affecting umami, sour and bitter tastes. These results suggest that the reciprocal and sequential regulatory mechanisms by ANG II (as an acute suppressor together with ALDO (as a slow enhancer on the salt taste sensitivity may exist in peripheral taste organs, contribute to salt intake, and play an important role in sodium homeostasis. Furthermore, the linkage between salty and sweet taste modulations via the ANG II signaling may optimize sodium and calorie intakes.

  9. Prosocial Signalling

    DEFF Research Database (Denmark)

    Kahsay, Goytom Abraha

    In contrast to the standard economic theory predictions, it seems clear that people do spend their time and resource to benefit others. Many lab and field experiment studies show that people display prosocial preferences such as altruism, reciprocity and conditional cooperation, fairness, etc...... signalling can cause reverse price reactions resembling the crowding-out of pre-existing motives for prosocial behavior seen in situations of volunteering and charitable giving. Using a unique combination of questionnaire and purchase panel data, it presents evidence of such reputation-driven reverse price...

  10. Sustainable Land Use Requires Attention to Ecological Signals

    Science.gov (United States)

    Halvorson, W.L.; Castellanos, A.E.; Murrieta-Saldivar, J.

    2003-01-01

    This case study details the difficulties of landscape management, highlighting the challenges inherent in managing natural resources when multiple agencies are involved, when the land users have no incentive for conservation, and when government agencies have too few resources for effective management. Pumping of groundwater from the aquifer of La Costa de Hermosillo in the state of Sonora, Mexico, began in 1945 and developed so quickly that by the late 1950s salinity intrusion from the Gulf of California was occurring in the wells. In the 1970s, the irrigatable land in La Costa peaked at 132,516 ha and the extracted volume of water from the aquifer peaked at around 1.14 billion cubic meters annually. By the 1980s, 105 wells of the total of 498 were contaminated with seawater and, therefore, identified for closure. At present La Costa de Hermosillo still represents 15% of the total harvested land, 16% of the total annual production, and 23% of the gross agricultural production of the state of Sonora. However, there are approximately 80,000 ha of abandoned fields due to salt water intension, lack of water and/or lack of credit available to individual farmers. This unstable situation resulted from the interplay of water management policies and practices, and farm-land policies and practices. While government agencies have been able to enforce better water use for agricultural production, there remains a significant area that requires restoration from its degraded state. For this piece of the ecosystem management puzzle, government agencies have thus far been unable to affect a solution.

  11. Insulin and Insulin-like Growth Factor II Differentially Regulate Endocytic Sorting and Stability of Insulin Receptor Isoform A*

    Science.gov (United States)

    Morcavallo, Alaide; Genua, Marco; Palummo, Angela; Kletvikova, Emilia; Jiracek, Jiri; Brzozowski, Andrzej M.; Iozzo, Renato V.; Belfiore, Antonino; Morrione, Andrea

    2012-01-01

    The insulin receptor isoform A (IR-A) binds both insulin and insulin-like growth factor (IGF)-II, although the affinity for IGF-II is 3–10-fold lower than insulin depending on a cell and tissue context. Notably, in mouse embryonic fibroblasts lacking the IGF-IR and expressing solely the IR-A (R−/IR-A), IGF-II is a more potent mitogen than insulin. As receptor endocytosis and degradation provide spatial and temporal regulation of signaling events, we hypothesized that insulin and IGF-II could affect IR-A biological responses by differentially regulating IR-A trafficking. Using R−/IR-A cells, we discovered that insulin evoked significant IR-A internalization, a process modestly affected by IGF-II. However, the differential internalization was not due to IR-A ubiquitination. Notably, prolonged stimulation of R−/IR-A cells with insulin, but not with IGF-II, targeted the receptor to a degradative pathway. Similarly, the docking protein insulin receptor substrate 1 (IRS-1) was down-regulated after prolonged insulin but not IGF-II exposure. Similar results were also obtained in experiments using [NMeTyrB26]-insulin, an insulin analog with IR-A binding affinity similar to IGF-II. Finally, we discovered that IR-A was internalized through clathrin-dependent and -independent pathways, which differentially regulated the activation of downstream effectors. Collectively, our results suggest that a lower affinity of IGF-II for the IR-A promotes lower IR-A phosphorylation and activation of early downstream effectors vis à vis insulin but may protect IR-A and IRS-1 from down-regulation thereby evoking sustained and robust mitogenic stimuli. PMID:22318726

  12. Signal processing for cognitive radios

    CERN Document Server

    Jayaweera, Sudharman K

    2014-01-01

    This book covers power electronics, in depth, by presenting the basic principles and application details, and it can be used both as a textbook and reference book.  Introduces the specific type of CR that has gained the most research attention in recent years: the CR for Dynamic Spectrum Access (DSA). Provides signal processing solutions to each task by relating the tasks to materials covered in Part II. Specialized chapters then discuss specific signal processing algorithms required for DSA and DSS cognitive radios  

  13. Sustainable Procurement: Integrating Classroom Learning with University Sustainability Programs

    Science.gov (United States)

    Goldschmidt, Kyle; Harrison, Terry; Holtry, Matthew; Reeh, Jeremy

    2013-01-01

    Organizations are facing increased pressure from various stakeholders to address issues of sustainability, resulting in a growing demand for sustainability education and training. Procurement groups remain the key drivers of many sustainability-related strategies, placing pressure on universities to integrate sustainability concepts into the…

  14. EBR-II Data Digitization

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Su-Jong [Idaho National Lab. (INL), Idaho Falls, ID (United States); Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Sackett, John [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-08-01

    1. Objectives To produce a validation database out of those recorded signals it will be necessary also to identify the documents need to reconstruct the status of reactor at the time of the beginning of the recordings. This should comprehends the core loading specification (assemblies type and location and burn-up) along with this data the assemblies drawings and the core drawings will be identified. The first task of the project will be identify the location of the sensors, with respect the reactor plant layout, and the physical quantities recorded by the Experimental Breeder Reactor-II (EBR-II) data acquisition system. This first task will allow guiding and prioritizing the selection of drawings needed to numerically reproduce those signals. 1.1 Scopes and Deliverables The deliverables of this project are the list of sensors in EBR-II system, the identification of storing location of those sensors, identification of a core isotopic composition at the moment of the start of system recording. Information of the sensors in EBR-II reactor system was summarized from the EBR-II system design descriptions listed in Section 1.2.

  15. Ni(II), Cu(II) and Zn(II)

    African Journals Online (AJOL)

    Chemical speciation of citric acid complexes of Co(II), Ni(II), Cu(II) and Zn(II) was investigated pH-metrically in 0.0-2.5% anionic, cationic and neutral micellar media. The primary alkalimetric data were pruned with SCPHD program. The existence of different binary species was established from modeling studies using the ...

  16. Ni(II), Cu(II) and Zn(II)

    African Journals Online (AJOL)

    NICO

    2010-06-15

    Jun 15, 2010 ... physico-chemical techniques. A square planar geometry was suggested for Cu(II) and octahedral geometry proposed for Co(II),. Ni(II) and Zn(II). TG curves indicated that the complexes decompose in three to four steps. The presence of coordinated water in metal complexes was confirmed by thermal and ...

  17. Ecologically sustainable development in dairy farms II: Nutrient cycling

    Science.gov (United States)

    In Mexico, there is not a specific regulation dealing with manure and wastewater in confined livestock farms. In the case of dairy farms that have agricultural areas for the production of forage crops, there are some "Good Management Practices", focused on the use of manure as a source of nitrogen a...

  18. Sustainability of the Benefits Derived from Fadama II Critical ...

    African Journals Online (AJOL)

    USER

    national minimum wage of N18,000 as a benchmark for living wage in Nigeria, the majority of beneficiaries (91%) could be considered to be earning modest income which may be an outcome of the successful implementation of the. Fadama projects in the area (Nkonya, Philip, Pender et al, 2008). Table 1: Socioeconomic ...

  19. C-terminal Src Kinase Gates Homeostatic Synaptic Plasticity and Regulates Fasciclin II Expression at the Drosophila Neuromuscular Junction.

    Directory of Open Access Journals (Sweden)

    Ashlyn M Spring

    2016-02-01

    Full Text Available Forms of homeostatic plasticity stabilize neuronal outputs and promote physiologically favorable synapse function. A well-studied homeostatic system operates at the Drosophila melanogaster larval neuromuscular junction (NMJ. At the NMJ, impairment of postsynaptic glutamate receptor activity is offset by a compensatory increase in presynaptic neurotransmitter release. We aim to elucidate how this process operates on a molecular level and is preserved throughout development. In this study, we identified a tyrosine kinase-driven signaling system that sustains homeostatic control of NMJ function. We identified C-terminal Src Kinase (Csk as a potential regulator of synaptic homeostasis through an RNAi- and electrophysiology-based genetic screen. We found that Csk loss-of-function mutations impaired the sustained expression of homeostatic plasticity at the NMJ, without drastically altering synapse growth or baseline neurotransmission. Muscle-specific overexpression of Src Family Kinase (SFK substrates that are negatively regulated by Csk also impaired NMJ homeostasis. Surprisingly, we found that transgenic Csk-YFP can support homeostatic plasticity at the NMJ when expressed either in the muscle or in the nerve. However, only muscle-expressed Csk-YFP was able to localize to NMJ structures. By immunostaining, we found that Csk mutant NMJs had dysregulated expression of the Neural Cell Adhesion Molecule homolog Fasciclin II (FasII. By immunoblotting, we found that levels of a specific isoform of FasII were decreased in homeostatically challenged GluRIIA mutant animals-but markedly increased in Csk mutant animals. Additionally, we found that postsynaptic overexpression of FasII from its endogenous locus was sufficient to impair synaptic homeostasis, and genetically reducing FasII levels in Csk mutants fully restored synaptic homeostasis. Based on these data, we propose that Csk and its SFK substrates impinge upon homeostatic control of NMJ function by

  20. Towards sustainable development

    Science.gov (United States)

    Munn, R. E.

    Sustainable development is a difficult phrase to define, particularly in the context of human ecosystems. Questions have to be asked, such as "Sustainable for whom?" "Sustainable for what purposes?" "Sustainable at the subsistence or at the luxury level?" and "Sustainable under what conditions?" In this paper, development is taken to mean improving the quality of life. (If development were to mean growth, then it could not be sustained over the long term.) Studies of development must, of course, consider economic factors, particularly in the case of societies who suffer from the pollution of poverty. However, cultural and environmental factors are equally important. In fact, development is not sustainable over the long term if it is not ecologically sustainable. The terms maximum sustainable yield of a renewable resource, carrying capacity of a region and assimilative capacity of a watershed or airshed are discussed. Approaches using these resource management tools are recommended when external conditions are not changing very much. The problem today is that unprecedented rates of change are expected in the next century, not only of environmental conditions such as climate but also of socioeconomic conditions such as renewable resource consumption and populations (of both people and of automobiles)! In rapidly changing situations, policies must be adopted that strengthen resilence and ecosystem integrity; that is, society must increase its ability to adapt. Maintaining the status quo is a long-term prescription for disaster. The problem is of course that little is known about how to design strategies that will increase resilience and ecosystem integrity, and this area of research needs to be strengthened. Some suggestions on appropriate indicators of ecosystem integrity are given in the paper but these need considerable refinement. One of the main problems with long-term environmental policy formulation is the uncertainty to be expected, including the possibility

  1. Sustainable Consumption Dilemmas

    Directory of Open Access Journals (Sweden)

    Kees Vringer

    2017-06-01

    Full Text Available To examine which considerations play a role when individuals make decisions to purchase sustainable product varieties or not, we have conducted a large scale field experiment with more than 600 participating households. Households can vote on whether the budgets they receive should only be spent on purchasing the sustainable product variety, or whether every household in a group is free to spend their budget on any product variety. By conducting several treatments, we tested whether people tend to view sustainable consumption as a social dilemma or as a moral dilemma. We find little support for the hypothesis that social dilemma considerations are the key drivers of sustainable consumption behaviour. Participants seem to be caught in a moral dilemma in which they not only weigh their individual financial costs with the sustainable benefits but they also consider the consequences of restricting other people’s freedom of choice. Complementary survey results further substantiate this claim and show that many people are reluctant to impose restrictions on their peers, but, at the same time, our results also suggest substantial support for the government to regulate the availability of unsustainable product varieties.

  2. Governance Strategies for a Sustainable Digital World

    Directory of Open Access Journals (Sweden)

    Igor Linkov

    2018-02-01

    Full Text Available Digitalization is changing society by the increased connectivity and networking that digital technologies enable, such as enhancing communication, services, and trade. Increasingly, policymakers within various national governments and international organizations such as the United Nations (UN and Organization for Economic Co-operation and Development (OECD are examining the original sustainability policy concepts applied within the Brundtland Report of 1987 through the lens of digitalization. While the growth of a digital economy may increase productivity and benefit local and global economies, digitalization also raises potential sustainability challenges pertaining to social (i.e., the benefits or costs imposed by disruptive digital technologies upon social networks and ways of life, including threats to economic sustainability and the rise of economic disparity and environmental wellbeing (i.e., natural resource stewardship and concern for future generations driven by the automation of information processing and delivery of services. Various perspectives have been raised regarding how the process of digitalization might be governed, and national governments remain at odds regarding a single best strategy to promote sustainable digitalization using the Brundtland concept to meet the development needs of the present without compromising the needs of future generations (i.e., social and environmental well-being. This paper reviews three governance strategies that countries can use in conjunction with adaptive governance to respond to digitalization sustainability threats: (i a laissez-faire, industry-driven approach; (ii a precautionary and preemptive strategy on the part of government; and (iii a stewardship and “active surveillance” approach by government agencies that reduce the risks derived from digitalization while promoting private sector innovation. Regardless of a state’s digital governance response and how it is shaped by

  3. HVEM signalling promotes colitis.

    Directory of Open Access Journals (Sweden)

    Corinne Schaer

    Full Text Available BACKGROUND: Tumor necrosis factor super family (TNFSF members regulate important processes involved in cell proliferation, survival and differentiation and are therefore crucial for the balance between homeostasis and inflammatory responses. Several members of the TNFSF are closely associated with inflammatory bowel disease (IBD. Thus, they represent interesting new targets for therapeutic treatment of IBD. METHODOLOGY/PRINCIPAL FINDINGS: We have used mice deficient in TNFSF member HVEM in experimental models of IBD to investigate its role in the disease process. Two models of IBD were employed: i chemical-induced colitis primarily mediated by innate immune cells; and ii colitis initiated by CD4(+CD45RB(high T cells following their transfer into immuno-deficient RAG1(-/- hosts. In both models of disease the absence of HVEM resulted in a significant reduction in colitis and inflammatory cytokine production. CONCLUSIONS: These data show that HVEM stimulatory signals promote experimental colitis driven by innate or adaptive immune cells.

  4. Sustainability and sacred values

    Directory of Open Access Journals (Sweden)

    John Cairns Jr.

    2002-09-01

    Full Text Available Successful implementation of the quest for sustainable use of the planet requires that human society both reexamine and expand present views of what is sacred and what is not. The most important aspect will be going beyond a homocentric focus to a biocentric emphasis. A unifying theme would be the desire to leave a habitable planet for human descendants and those of other species. It is unlikely that society can be confident of achieving sustainability until persuasive evidence supporting this belief has existed for several generations. In order for sustainable use of the planet to persist indefinitely, the conditions essential to this state must be morally preserved on sacred grounds. Viewing natural systems as sacred requires not only preventing damage to them but, wherever possible, repairing damage to them caused by humankind.

  5. Sustainability & Organization Design

    DEFF Research Database (Denmark)

    Rasmussen, Morten Bygvraa; Obel, Børge; Kallehave, Pernille

    of global governance to match the new dynamics and consequences of globalization. Governments are re-examining corporate accountability to society and how companies earn their license to operate. Furthermore companies are re-examining their code of conduct and leadership values. Thus, sustainability...... is an important driver in organizations and its impact and effect on organization design is critical. Development of organization design, structure, processes, and human skills and values are needed to create the sustainable organization for the future. This paper discusses the requirements to be a sustainable...... organization. Here we follow the Global Compact criteria. The consequences for processes, structure, and human skills and values are analyzed. In particular the analysis will investigate exploration and exploitation from a holistic perspective using the principles of requisite variety and information...

  6. QUEST for sustainable CPD

    DEFF Research Database (Denmark)

    Nielsen, Birgitte Lund

    2014-01-01

    in the local learning communities we have seen a positive trend from the first to the last course-module, but with great variation between schools. Factors potentially supporting sustainable development seem to be about (1) continuingly scaffolding teachers’ collaborative inquiries by organizing activities......Continuous Professional Development (CPD) can be crucial for reforming science teaching, but more knowledge is needed about how to support sustainability of the effects. The Danish QUEST project is a large scale, long-term collaborative CPD project designed according to widely agreed criteria...... phase. The findings are discussed looking forward to the institutionalization phase identifying factors potentially supporting sustainable development pertaining to local science teachers developing a shared focus on student learning in science, and perceived individual and collective efficacy...

  7. Sustainable urban development

    DEFF Research Database (Denmark)

    Jensen, Jesper Ole; Christensen, Toke Haunstrup; Gram-Hanssen, Kirsten

    Sustainability in urban planning has a long history and it has been a widespread solution to build high and compact in order to minimise the need for transportation, land use and heating. Recent research, however, points towards the need for a supplementary approach which includes the consumer...... behaviour of the household. This approach necessarily has to work from below and include the citizens, as it is their daily practices that have to be challenged. This article reviews the literature of to what extent compact cities are the most sustainable and it use lifestyle interpretations of urbane forms...... to challenge the compact cities approach. As an alternative or supplementary approach the article introduce practice theory as a way to understand consumption and it gives examples on how this approach can be used to inspire local authorities to alternative and supplementary strategies of achieving sustainable...

  8. Sustainable Consumption: Research Challenges

    DEFF Research Database (Denmark)

    Reisch, Lucia A.; Cohen, Maurie J.; Thøgersen, John

    The Board of the Swedish Foundation for Strategic Environmental Research (Mistra) decided in October 2015 that a proposal for a funding application call in the research area of “sustainable consumption” should be drawn up. According to the statutes of Mistra, research funded by the foundation...... for achieving industrial applications shall be taken advantage of.” The funding application call to be developed by Mistra is to be based on an analysis of the current state of the art of research and of society’s knowledge needs regarding sustainable consumption. Mistra commissioned a committee of four...... the orientation of a new research program to be used as draft text for the call for funding applications. The aim of this background report is hence to shed light on future research topics within sustainable consumption from a Swedish perspective. The research pro- moted should help to develop Sweden...

  9. Sustainable Supply Chain Design

    DEFF Research Database (Denmark)

    Bals, Lydia; Tate, Wendy

    A significant conceptual and practical challenge is how to integrate triple bottom line (TBL; including economic, social and environmental) sustainability into global supply chains. Although this integration is necessary to slow down global resource depletion, understanding is limited of how...... to implement TBL goals across the supply chain. In supply chain design, the classic economic perspective still dominates, although the idea of the TBL is more widely disseminated. The purpose of this research is to add to the sustainable supply chain management literature (SSCM) research agenda...... by incorporating the physical chain, and the (information and financial) support chains into supply chain design. This manuscript tackles issues of what the chains are designed for and how they are designed structurally. Four sustainable businesses are used as illustrative case examples of innovative supply chain...

  10. Sustainability in a nutshell.

    Science.gov (United States)

    Silvertown, Jonathan

    2004-06-01

    Sustainable exploitation is widely advocated as a strategy for reconciling economic pressures upon natural habitats with nature conservation. Two recent papers examine different aspects of the sustainability of the nut harvest on wild populations of Brazil nut trees Bertholletia excelsa in Amazonia. Peres et al. find that many populations of the Brazil nut tree lack juvenile trees and are not regenerating. In a socioeconomic study, Escobal and Aldana find that nut-gathering provides insufficient income on its own to support nut-gatherers and that their other income-raising activities damage the forest. The existence of a market for rainforest products is, therefore, not sufficient on its own to prevent habitat destruction or the overexploitation of the resource and a more sophisticated approach to sustainability is required. Development of a market in ethically traded Brazil nuts might be one solution.

  11. TOURISM AND SUSTAINABLE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Gina Ionela Butnaru

    2014-06-01

    Full Text Available Tourism and sustainable development are the subject of many initiatives and public or private debates in Romania. The main problem to which these initiatives try to find an answer is mostly related to the income generation for the local communities by using rationally and efficiently the local potential, in agreement with the economic, social, natural, and cultural factors. Consequently, some measures should be taken, and the tourist sector as a whole needs all the methods of sustainable development: new technologies, change of social behaviour, change of environmental legislation, methods of environmental management, better planning and development of control procedures. In this article, we presented a model of tourism development which should be applied in all the regions of great tourist attraction, and we realised a synthesis of the socio-economic advantages of sustainable tourism.

  12. Is Globalisation Sustainable?

    Directory of Open Access Journals (Sweden)

    Mohsin Raza

    2010-01-01

    Full Text Available It is clear that globalisation is something more than a purely economic phenomenon manifesting itself on a global scale. Among the visible manifestations of globalisation are the greater international movement of goods and services, financial capital, information and people. In addition, there are technological developments, more international cultural exchanges, facilitated by the freer trade of more differentiated products as well as by tourism and immigration, changes in the political landscape and ecological consequences. In this paper, we link the Maastricht Globalisation Index with Sustainability Indices to analyse if more globalised countries are doing better in terms of sustainable development and its dimensions. The results seem to suggest that the process of globalisation may render world development more sustainable.

  13. Digital signal processing an experimental approach

    CERN Document Server

    Engelberg, Shlomo

    2008-01-01

    Digital Signal Processing is a mathematically rigorous but accessible treatment of digital signal processing that intertwines basic theoretical techniques with hands-on laboratory instruction. Divided into three parts, the book covers various aspects of the digital signal processing (DSP) ""problem."" It begins with the analysis of discrete-time signals and explains sampling and the use of the discrete and fast Fourier transforms. The second part of the book???covering digital to analog and analog to digital conversion???provides a practical interlude in the mathematical content before Part II

  14. ANALYSIS ON SUSTAINABILITY OF TOURISM BUSINESS

    Directory of Open Access Journals (Sweden)

    Faradesi Ardialisa

    2012-09-01

    Full Text Available The objectives of the research were to understand indicators of business sustainability tourism from stakeholders’ perspectives in relation to 3P (People, Planet, Profit, to understand how the concept of sustainability is operationalized in the Pancawati group in relation to 3P (People, Planet, Profit, and to map the value chain of Lembur Pancawati as the case in Ecotourism in Bogor. The methodology used was qualitative descriptive practice-oriented business research with single case study. Based on the stakeholder analysis in Bogor tourism, the indicators of sustainable business in tourism are: (i Involvement from local people, (ii Preservation of nature and local culture, (iii Availability of nature Education program, (iv Strong commitment from business owner/leader, (v Sufficient capital to support the initial business establishment, (vi Availability of various networks. The operationalization in Pancawati Group was observed to have item i, iii, and iv partially implemented and the rest was fully implemented. The position of Pancawati Group in value chain was as main firm, as it acted as multiple actors in the chain. In order to have all indicators implemented, it was suggested to have public private partnership in place.Keywords: Sustainable Tourism, Value Chain, Qualitative Methods

  15. Sustainable use of phosphorus: a finite resource.

    Science.gov (United States)

    Scholz, Roland W; Ulrich, Andrea E; Eilittä, Marjatta; Roy, Amit

    2013-09-01

    Phosphorus is an essential element of life and of the modern agricultural system. Today, science, policy, agro-industry and other stakeholder groups are increasingly concerned about the sustainable use of this resource, given the dissipative nature of phosphorus and difficulties in assessing, evaluating, and coping with phosphorus pollution in aquatic and terrestrial systems. We argue that predictions about a forthcoming peak, followed by a quick reduction (i.e., physical phosphate rock scarcity) are unreasoned and stress that access to phosphorus (economic scarcity) is already, and may increasingly become critical, in particular for smallholders farmers in different parts of the world. The paper elaborates on the design, development, goals and cutting-edge contributions of a global transdisciplinary process (i.e. mutual learning between science and society including multiple stakeholders) on the understanding of potential contributions and risks related to the current mode of using phosphorus on multiple scales (Global TraPs). While taking a global and comprehensive view on the whole phosphorus-supply chain, Global TraPs organizes and integrates multiple transdisciplinary case studies to better answer questions which inform sustainable future phosphorus use. Its major goals are to contribute to four issues central to sustainable resource management: i) long-term management of biogeochemical cycles, in particular the challenge of closing the phosphorus cycle, ii) achieving food security, iii) avoiding environmental pollution and iv) sustainability learning on a global level by transdisciplinary processes. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. USAF Logistics Process Optimization Study for the Aircraft Asset Sustainment Process. Volume 1

    National Research Council Canada - National Science Library

    Adamson, Anthony

    1998-01-01

    .... It is published as three separate volumes. Volume I, USAF Logistics Process Optimization Study for the Aircraft Asset Sustainment Process -- Phase II Report, discusses the result and cost/benefit analysis of testing three initiatives...

  17. USAF Logistics Process Optimization Study for the Aircraft Asset Sustainment Process. Volume 2

    National Research Council Canada - National Science Library

    Adamson, Anthony

    1998-01-01

    .... It is published as three separate volumes. Volume I, USAF Logistics Process Optimization Study for the Aircraft Asset Sustainment Process -- Phase II Report, discusses the result and cost/benefit analysis of testing three initiatives...

  18. The Fiction of Sustainability

    DEFF Research Database (Denmark)

    Mubanda Rasmussen, Louise

    at maintaining and attracting new donor funding? Despite this contradiction, various actors in the HIV/AIDS field continuously invoke the doctrine of sustainability (Swidler & Watkins) as the remedy for problems such as 'donor dependency' and 'high turn-over' among volunteers. Based on five months ethnographic...... research with organisations providing help to "Orphans and Vulnerable Children" in Malawi, this paper discusses how donors, international and local NGOs, and CBOs all participate in keeping alive 'the fiction of sustainability', each for their different reasons. Rather than overt resistance to the power...

  19. Environment and sustainability

    DEFF Research Database (Denmark)

    Paavola, Jouni; Røpke, Inge

    2015-01-01

    This chapter reviews socio-economic research on the environment and sustainability. The chapter first explores core aspects of socio-economics, examines how socio-economics has related to the agenda of research on the environment, and assesses how socio-economic research on the environment became...... to a research agenda for ‘socio-ecological economics’. Sustainable consumption and global environmental change are already important areas of research for it. But ecological macroeconomics is also needed to formulate coordinated responses to multiple crises such as economic downturn, climate change and loss...

  20. Developing Ecological Sustainability

    DEFF Research Database (Denmark)

    Hedman, Jonas; Henningsson, Stefan

    2016-01-01

    IS initiatives become part of a firm’s overall strategy and part of the organizational sustainability process. We find that Green IS initiatives are initiated through a bottom-up process where environmentally concerned individuals identify issues and become Green IS champions. They use their authority...... and edification skills to promote Green IS to the organizational agenda. If the issue is aligned with the organizational agenda, it receives management’s endorsement. The empirical case also shows two types of systemic feedback that can fuel a self-reinforcing sustainability process. The first type of feedback...