Functional photoacoustic imaging to observe regional brain activation induced by cocaine hydrochloride

NASA Astrophysics Data System (ADS)

Jo, Janggun; Yang, Xinmai

2011-09-01

Photoacoustic microscopy (PAM) was used to detect small animal brain activation in response to drug abuse. Cocaine hydrochloride in saline solution was injected into the blood stream of Sprague Dawley rats through tail veins. The rat brain functional change in response to the injection of drug was then monitored by the PAM technique. Images in the coronal view of the rat brain at the locations of 1.2 and 3.4 mm posterior to bregma were obtained. The resulted photoacoustic (PA) images showed the regional changes in the blood volume. Additionally, the regional changes in blood oxygenation were also presented. The results demonstrated that PA imaging is capable of monitoring regional hemodynamic changes induced by drug abuse.

CORRELATIONS OF PESTICIDE-INDUCED CHOLINESTERASE INHIBITION AND MOTOR ACTIVITY CHANGES IN ADULT RATS.

EPA Science Inventory

The acute neurobehavioral effects of acetylcholinesterase-inhibiting pesticides are primarily due to overstimulation of the cholinergic system. Lowered motor activity levels represent a sensitive endpoint with which to monitor functional changes in laboratory animals exposed to ...

Comparison of the Data Products from Different Instrument Types with Application to Induced Seismic Monitoring Framework

NASA Astrophysics Data System (ADS)

Yenier, E.; Baturan, D.; Karimi, S.; Moores, A. O.; Spriggs, N.

2016-12-01

Earthquakes may be induced by man-made activity in the vicinity of critically-stressed fault segments. A number of earthquakes characterized as induced with magnitudes M>3 were recorded in British Columbia, Alberta, Oklahoma and Ohio, since 2013. In response to growing induced seismicity in North America, many jurisdictions have mandated near real-time seismic monitoring around operation sites. The data products from monitoring networks are used as drivers of operational traffic light systems designed to mitigate risks associated with induced seismicity. Most traffic light protocols developed to date use staged thresholds of earthquake magnitudes. Additionally, ground motions, which are used to estimate the impact of earthquakes and specify seismic hazard, have been proposed as an enhancement to the existing protocols. There are several challenges and options to consider at the time of planning and designing a monitoring network, the most important of which is the choice of ground motion sensing technology. In order to accurately estimate event source parameters and ground motions, monitoring instruments have to record and image the low-frequency plateau and the corner frequency of the anticipated event spectrum. A flat response over a wide frequency range with a wide dynamic range is desired for a maximum benefit from ground motion products. This study evaluates the performance of three types of instruments in terms of their suitability for induced seismic monitoring (ISM): broadband seismometers, accelerometers and geophones. Each instrument type is assessed in terms of self-noise, frequency response and clip level using instrument specifications and real-world ISM application data. The impact of each sensing technology on key ISM network performance criteria, event magnitude estimations and ground motion measurements are examined.

The estimation of hemodynamic signals measured by fNIRS response to cold pressor test

NASA Astrophysics Data System (ADS)

Ansari, M. A.; Fazliazar, E.

2018-04-01

The estimation of cerebral hemodynamic signals has an important role for monitoring the stage of neurological diseases. Functional Near-Infrared Spectroscopy (fNIRS) can be used for monitoring of brain activities. fNIRS utilizes light in the near-infrared spectrum (650-1000 nm) to study the response of the brain vasculature to the changes in neural activities, called neurovascular coupling, within the cortex when cognitive activation occurs. The neurovascular coupling may be disrupted in the brain pathological condition. Therefore, we can also use fNIRS to diagnosis brain pathological conditions or to monitor the efficacy of related treatments. The Cold pressor test (CPT), followed by immersion of dominant hand or foot in the ice water, can induce cortical activities. The perception of pain induced by CPT can be related to cortical neurovascular coupling. Hence, the variation of cortical hemodynamic signals during CPT can be an indicator for studying neurovascular coupling. Here, we study the effect of pain induced by CPT on the temporal variation of concentration of oxyhemoglobin [HbO2] and deoxyhemoglobin [Hb] in the healthy brains. We use fNIRS data collected on forehead during a CPT from 11 healthy subjects, and the average data are compared with post-stimulus pain rating scores. The results show that the variation of [Hb] and [HbO2] are positively correlated with self-reported scores during the CPT. These results depict that fNIRS can be potentially applied to study the decoupling of neurovascular process in brain pathological conditions.

Simultaneous multi-patch-clamp and extracellular-array recordings: Single neuron reflects network activity

NASA Astrophysics Data System (ADS)

Vardi, Roni; Goldental, Amir; Sardi, Shira; Sheinin, Anton; Kanter, Ido

2016-11-01

The increasing number of recording electrodes enhances the capability of capturing the network’s cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity.

Simultaneous multi-patch-clamp and extracellular-array recordings: Single neuron reflects network activity.

PubMed

Vardi, Roni; Goldental, Amir; Sardi, Shira; Sheinin, Anton; Kanter, Ido

2016-11-08

The increasing number of recording electrodes enhances the capability of capturing the network's cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity.

Simultaneous multi-patch-clamp and extracellular-array recordings: Single neuron reflects network activity

PubMed Central

Vardi, Roni; Goldental, Amir; Sardi, Shira; Sheinin, Anton; Kanter, Ido

2016-01-01

The increasing number of recording electrodes enhances the capability of capturing the network’s cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity. PMID:27824075

Induced cytochrome P450 1A activity in cichlid fishes from Guandu River and Jacarepaguá Lake, Rio de Janeiro, Brazil.

PubMed

Parente, Thiago E M; De-Oliveira, Ana C A X; Paumgartten, Francisco J R

2008-03-01

The induction of cytochrome P4501A-mediated activity (e.g. ethoxyresorufin-O-deethylation, EROD) has been used as a biomarker for monitoring fish exposure to AhR-receptor ligands such as polycyclic aromatic hydrocarbons (PAH), polychlorinated biphenyls (PCB) and polychlorinated dibenzo-dioxins/furans (PCDD/Fs). In this study we found that hepatic EROD is induced in fish ("Nile tilapia", Oreochromis niloticus and "acará", Geophagus brasiliensis) from the Guandu River (7-17-fold) and Jacarepaguá Lake (7-fold), Rio de Janeiro, Brazil. Since both cichlid fish are consumed by the local population and the Guandu River is the main source of the drinking water supply for the greater Rio de Janeiro metropolitan area, pollution by cytochrome P4501A-inducing chemicals is a cause for concern and should be further investigated in sediments, water and biota. We additionally showed that EROD activity in the fish liver post-mitochondrial supernatant-simpler, cheaper and less time consuming to prepare than the microsomal fraction-is sufficiently sensitive for monitoring purposes.

Live morphological analysis of taxol-induced cytoplasmic vacuolization [corrected] in human lung adenocarcinoma cells.

PubMed

Wang, Xiao-Ping; Chen, Tong-Sheng; Sun, Lei; Cai, Ji-Ye; Wu, Ming-Qian; Mok, Martin

2008-12-01

Taxol (paclitaxel), one of the most active cancer chemotherapeutic agents, can cause programmed cell death (PCD) and cytoplasmic vacuolization. The objective of this study was to analyze the morphological characteristics induced by taxol. Human lung adenocarcinoma (ASTC-a-1) cells were exposed to various concentration of taxol. CCK-8 was used to assay the cell viability. Atomic force microscopy (AFM), plasmid transfection and confocal fluorescence microscopy were performed to image the cells morphological change induced by taxol. Fluorescence resonance energy transfer (FRET) was used to monitor the caspase-3 activation in living cells during taxol-induced cell death. Cells treated with taxol exhibited significant swelling and cytoplasmic vacuolization which may be due to endoplasmic reticulum (ER) vacuolization. Caspase-3 was not activated during taxol-induced cytoplasmic vacuolization and cell death. These findings suggest that taxol induces caspase-3-independent cytoplasmic vacuolization, cell swelling and cell death through ER vacuolization.

Lysophosphatidic Acid Promotes Cell Migration through STIM1- and Orai1-Mediated Ca2+i Mobilization and NFAT2 Activation

PubMed Central

Jans, Ralph; Mottram, Laura; Johnson, Darren L; Brown, Anna M; Sikkink, Stephen; Ross, Kehinde; Reynolds, Nick J

2013-01-01

Lysophosphatidic acid (LPA) enhances cell migration and promotes wound healing in vivo, but the intracellular signaling pathways regulating these processes remain incompletely understood. Here we investigated the involvement of agonist-induced Ca2+ entry and STIM1 and Orai1 proteins in regulating nuclear factor of activated T cell (NFAT) signaling and LPA-induced keratinocyte cell motility. As monitored by Fluo-4 imaging, stimulation with 10 μℳ LPA in 60 μℳ Ca2+o evoked Ca2+i transients owing to store release, whereas addition of LPA in physiological 1.2 mℳ Ca2+o triggered store release coupled to extracellular Ca2+ entry. Store-operated Ca2+ entry (SOCE) was blocked by the SOCE inhibitor diethylstilbestrol (DES), STIM1 silencing using RNA interference (RNAi), and expression of dominant/negative Orai1R91W. LPA induced significant NFAT activation as monitored by nuclear translocation of green fluorescent protein-tagged NFAT2 and a luciferase reporter assay, which was impaired by DES, expression of Orai1R91W, and inhibition of calcineurin using cyclosporin A (CsA). By using chemotactic migration assays, LPA-induced cell motility was significantly impaired by STIM1, CsA, and NFAT2 knockdown using RNAi. These data indicate that in conditions relevant to epidermal wound healing, LPA induces SOCE and NFAT activation through Orai1 channels and promotes cell migration through a calcineurin/NFAT2-dependent pathway. PMID:23096711

An overview of existing raptor contaminant monitoring activities in Europe.

PubMed

Gómez-Ramírez, P; Shore, R F; van den Brink, N W; van Hattum, B; Bustnes, J O; Duke, G; Fritsch, C; García-Fernández, A J; Helander, B O; Jaspers, V; Krone, O; Martínez-López, E; Mateo, R; Movalli, P; Sonne, C

2014-06-01

Biomonitoring using raptors as sentinels can provide early warning of the potential impacts of contaminants on humans and the environment and also a means of tracking the success of associated mitigation measures. Examples include detection of heavy metal-induced immune system impairment, PCB-induced altered reproductive impacts, and toxicity associated with lead in shot game. Authorisation of such releases and implementation of mitigation is now increasingly delivered through EU-wide directives but there is little established pan-European monitoring to quantify outcomes. We investigated the potential for EU-wide coordinated contaminant monitoring using raptors as sentinels. We did this using a questionnaire to ascertain the current scale of national activity across 44 European countries. According to this survey, there have been 52 different contaminant monitoring schemes with raptors over the last 50years. There were active schemes in 15 (predominantly western European) countries and 23 schemes have been running for >20years; most monitoring was conducted for >5years. Legacy persistent organic compounds (specifically organochlorine insecticides and PCBs), and metals/metalloids were monitored in most of the 15 countries. Fungicides, flame retardants and anticoagulant rodenticides were also relatively frequently monitored (each in at least 6 countries). Common buzzard (Buteo buteo), common kestrel (Falco tinnunculus), golden eagle (Aquila chrysaetos), white-tailed sea eagle (Haliaeetus albicilla), peregrine falcon (Falco peregrinus), tawny owl (Strix aluco) and barn owl (Tyto alba) were most commonly monitored (each in 6-10 countries). Feathers and eggs were most widely analysed although many schemes also analysed body tissues. Our study reveals an existing capability across multiple European countries for contaminant monitoring using raptors. However, coordination between existing schemes and expansion of monitoring into Eastern Europe is needed. This would enable assessment of the appropriateness of the EU-regulation of substances that are hazardous to humans and the environment, the effectiveness of EU level mitigation policies, and identify pan-European spatial and temporal trends in current and emerging contaminants of concern. Copyright © 2014. Published by Elsevier Ltd.

Antithrombocytopenic activity of carpaine and alkaloidal extract of Carica papaya Linn. leaves in busulfan induced thrombocytopenic Wistar rats.

PubMed

Zunjar, Vishwanath; Dash, Ranjeet Prasad; Jivrajani, Mehul; Trivedi, Bhavna; Nivsarkar, Manish

2016-04-02

The decoction of Carica papaya Linn. leaves is used in folklore medicine in certain parts of Malaysia and Indonesia for the treatment of different types of thrombocytopenia associated with diseases and drugs. There are several scientific studies carried out on humans and animal models to confirm the efficacy of decoction of papaya leave for the treatment of disease induced and drug induced thrombocytopenia, however very little is known about the bio-active compounds responsible for the observed activity. The aim of present study was to identify the active phytochemical component of Carica papaya Linn. leaves decoction responsible for anti-thrombocytopenic activity in busulfan-induced thrombocytopenic rats. Antithrombocytopenic activity was assessed on busulfan induced thrombocytopenic Wistar rats. The antithrombocytopenic activity of different bio-guided fractions was evaluated by monitoring blood platelet count. Bioactive compound carpaine was isolated and purified by chromatographic methods and confirmed by spectroscopic methods (LC-MS and 1D/2D-1H/13C NMR) and the structure was confirmed by single crystal X-ray diffraction. Quantification of carpaine was carried out by LC-MS/MS equipped with XTerra(®) MS C18 column and ESI-MS detector using 90:10 CH3CN:CH3COONH4 (6mM) under isocratic conditions and detected with multiple reaction monitoring (MRM) in positive ion mode. Two different phytochemical groups were isolated from decoction of Carica papaya leaves: phenolics, and alkaloids. Out of these, only alkaloid fraction showed good biological activity. Carpaine was isolated from the alkaloid fraction and exhibited potent activity in sustaining platelet counts upto 555.50±85.17×10(9)/L with no acute toxicity. This study scientifically validates the popular usage of decoction of Carica papaya leaves and it also proves that alkaloids particularly carpaine present in the leaves to be responsible for the antithrombocytopenic activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Application and Evaluation of ALOS PALSAR Data for Monitoring of Mining Induced Surface Deformations Using Interferometric Techniques

NASA Astrophysics Data System (ADS)

Walter, Diana; Wegmuller, Urs; Spreckels, Volker; Busch, Wolfgang

2008-11-01

The main objective of the projects "Determination of ground motions in mining areas by interferometric analyses of ALOS data" (ALOS ADEN 3576, ESA) and "Monitoring of mining induced surface deformation" (ALOS-RA-094, JAXA) is to evaluate PALSAR data for surface deformation monitoring, using interferometric techniques. We present monitoring results of surface movements for an active hard coal colliery of the German hard coal mining company RAG Deutsche Steinkohle (RAG). Underground mining activities lead to ground movements at the surface with maximum subsidence rates of about 10cm per month for the test site. In these projects the L-band sensor clearly demonstrates the good potential for deformation monitoring in active mining areas, especially in rural areas. In comparison to C-band sensors we clearly observe advantages in resolving the high deformation gradients that are present in this area and we achieve a more complete spatial coverage than with C-band. Extensive validation data based on levelling data and GPS measurements are available within RAǴs GIS based database "GeoMon" and thus enable an adequate analysis of the quality of the interferometric results. Previous analyses confirm the good accuracy of PALSAR data for deformation monitoring in mining areas. Furthermore, we present results of special investigations like precision geocoding of PALSAR data and corner reflector analysis. At present only DInSAR results are obtained due to the currently available number of PALSAR scenes. For the future we plan to also apply Persistent Scatterer Interferometry (PSI) using longer series of PALSAR data.

Face-induced expectancies influence neural mechanisms of performance monitoring.

PubMed

Osinsky, Roman; Seeger, Jennifer; Mussel, Patrick; Hewig, Johannes

2016-04-01

In many daily situations, the consequences of our actions are predicted by cues that are often social in nature. For instance, seeing the face of an evaluator (e.g., a supervisor at work) may activate certain evaluative expectancies, depending on the history of prior encounters with that particular person. We investigated how such face-induced expectancies influence neurocognitive functions of performance monitoring. We recorded an electroencephalogram while participants completed a time-estimation task, during which they received performance feedback from a strict and a lenient evaluator. During each trial, participants first saw the evaluator's face before performing the task and, finally, receiving feedback. Therefore, faces could be used as predictive cues for the upcoming evaluation. We analyzed electrocortical signatures of performance monitoring at the stages of cue processing, task performance, and feedback reception. Our results indicate that, at the cue stage, seeing the strict evaluator's face results in an anticipatory preparation of fronto-medial monitoring mechanisms, as reflected by a sustained negative-going amplitude shift (i.e., the contingent negative variation). At the performance stage, face-induced expectancies of a strict evaluation rule led to increases of early performance monitoring signals (i.e., frontal-midline theta power). At the final stage of feedback reception, violations of outcome expectancies differentially affected the feedback-related negativity and frontal-midline theta power, pointing to a functional dissociation between these signatures. Altogether, our results indicate that evaluative expectancies induced by face-cues lead to adjustments of internal performance monitoring mechanisms at various stages of task processing.

Active Duty - U.S. Army Noise Induced Hearing Injury Surveillance Calendar Years 2009-2013

DTIC Science & Technology

2014-06-01

rates for sensorineural hearing loss, significant threshold shift, tinnitus , and Noise-Induced Hearing Loss. The intention is to monitor the morbidity...surveillance. These code groups include sensorineural hearing loss (SNHL), significant threshold shift (STS), noise-induced hearing loss (NIHL) and tinnitus ... Tinnitus ) was analyzed using a regression model to determine the trend of incidence rates from 2007 to the current year. Statistical significance of a

Quantification of fatigue cracking in CT specimens with passive and active piezoelectric sensing

NASA Astrophysics Data System (ADS)

Yu, Jianguo; Ziehl, Paul; Zarate, Boris; Caicedo, Juan; Yu, Lingyu; Giurgiutiu, Victor; Metrovich, Brian; Matta, Fabio

2010-04-01

Monitoring of fatigue cracks in steel bridges is of interest to bridge owners and agencies. Monitoring of fatigue cracks has been attempted with acoustic emission using either resonant or broadband sensors. One drawback of passive sensing is that the data is limited to that caused by growing cracks. In this work, passive emission was complemented with active sensing (piezoelectric wafer active sensors) for enhanced detection capabilities. Passive and active sensing methods were described for fatigue crack monitoring on specialized compact tension specimens. The characteristics of acoustic emission were obtained to understand the correlation of acoustic emission behavior and crack growth. Crack and noise induced signals were interpreted through Swansong II Filter and waveform-based approaches, which are appropriate for data interpretation of field tests. Upon detection of crack extension, active sensing was activated to measure the crack size. Model updating techniques were employed to minimize the difference between the numerical results and experimental data. The long term objective of this research is to develop an in-service prognostic system to monitor structural health and to assess the remaining fatigue life.

Biomarker responses in the bivalve Chlamys farreri to the water-soluble fraction of crude oil

NASA Astrophysics Data System (ADS)

Jiang, Fenghua; Zhang, Li; Yang, Baijuan; Zheng, Li; Sun, Chengjun

2015-07-01

To investigate the effect of the water soluble fraction of crude oil (WSF) on marine bivalves, the scallop Chlamys farreri was exposed to three WSF concentrations (0.18 mg/L, 0.32 mg/L, and 0.51 mg/L, respectively) in seawater. Petroleum hydrocarbon contents in scallops and a suite of enzymes [7-Ethoxyresorufin-O-deethylase (EROD), aryl hydrocarbon hydroxylase (AHH), glutathione S-transferase (GST), and glutathione peroxidase (GPx)] in gills and digestive glands were monitored over 10 days. The results revealed that WSF affected the activity of the four enzymes in the gills and digestive glands. EROD activity in the gills was significantly induced in most individuals of the three test groups, while in the digestive gland it was significantly induced in the low-concentration group within 4 days but was inhibited in the middle- and high-concentration groups on days 1, 4, and 10. AHH activity in the gills of all treatment groups was significantly induced on day 1. In the digestive gland, AHH activity was induced in most individuals from the treatment groups. In all treatment groups, GST activity was significantly inhibited from days 2 to 10 in the gills and was induced after day 4 in the digestive gland. GPx activity in the gills was significantly inhibited throughout the exposure period in all treatment groups. There was no overall significant difference in GPx activity in the digestive gland between the control and treatment groups. Our results also revealed that petroleum hydrocarbon concentrations in the tissues increased linearly with exposure time. EROD activity in the digestive gland and GST and GPx activity in the gill tissue were negatively correlated with petroleum hydrocarbon body burden. These enzymes play important roles in detoxification and can act as potential biomarkers for monitoring petroleum hydrocarbon contaminants in the marine environment.

Swing Boat: Inducing and Recording Locomotor Activity in a Drosophila melanogaster Model of Alzheimer’s Disease

PubMed Central

Berlandi, Johannes; Lin, Fang-Ju; Ambrée, Oliver; Rieger, Dirk; Paulus, Werner; Jeibmann, Astrid

2017-01-01

Recent studies indicate that physical activity can slow down progression of neurodegeneration in humans. To date, automated ways to induce activity have been predominantly described in rodent models. To study the impact of activity on behavior and survival in adult Drosophila melanogaster, we aimed to develop a rotating tube device “swing boat” which is capable of monitoring activity and sleep patterns as well as survival rates of flies. For the purpose of a first application, we tested our device on a transgenic fly model of Alzheimer’s disease (AD). Activity of flies was recorded in a climate chamber using the Drosophila Activity Monitoring (DAM) System connected to data acquisition software. Locomotor activity was induced by a rotating tube device “swing boat” by repetitively tilting the tubes for 30 min per day. A non-exercising group of flies was used as control and activity and sleep patterns were obtained. The GAL4-/UAS system was used to drive pan-neuronal expression of human Aβ42 in flies. Immunohistochemical stainings for Aβ42 were performed on paraffin sections of adult fly brains. Daily rotation of the fly tubes evoked a pronounced peak of activity during the 30 min exercise period. Pan-neuronal expression of human Aβ42 in flies caused abnormalities in locomotor activity, reduction of life span and elevated sleep fragmentation in comparison to wild type flies. Furthermore, the formation of amyloid accumulations was observed in the adult fly brain. Gently induced activity over 12 days did not evoke prominent effects in wild type flies but resulted in prolongation of median survival time by 7 days (32.6%) in Aβ42-expressing flies. Additionally, restoration of abnormally decreased night time sleep (10%) and reduced sleep fragmentation (28%) were observed compared to non-exercising Aβ42-expressing flies. On a structural level no prominent effects regarding prevalence of amyloid aggregations and Aβ42 RNA expression were detected following activity induction. The rotating tube device successfully induced activity in flies shown by quantitative activity analysis. Our setup enabled quantitative analysis of activity and sleep patterns as well as of survival rates. Induced activity in a Drosophila model of Alzheimer’s disease improved survival and ameliorated sleep phenotypes. PMID:28912696

The cAMP-induced G protein subunits dissociation monitored in live Dictyostelium cells by BRET reveals two activation rates, a positive effect of caffeine and potential role of microtubules.

PubMed

Tariqul Islam, A F M; Yue, Haicen; Scavello, Margarethakay; Haldeman, Pearce; Rappel, Wouter-Jan; Charest, Pascale G

2018-08-01

To study the dynamics and mechanisms controlling activation of the heterotrimeric G protein Gα2βγ in Dictyostelium in response to stimulation by the chemoattractant cyclic AMP (cAMP), we monitored the G protein subunit interaction in live cells using bioluminescence resonance energy transfer (BRET). We found that cAMP induces the cAR1-mediated dissociation of the G protein subunits to a similar extent in both undifferentiated and differentiated cells, suggesting that only a small number of cAR1 (as expressed in undifferentiated cells) is necessary to induce the full activation of Gα2βγ. In addition, we found that treating cells with caffeine increases the potency of cAMP-induced Gα2βγ activation; and that disrupting the microtubule network but not F-actin inhibits the cAMP-induced dissociation of Gα2βγ. Thus, microtubules are necessary for efficient cAR1-mediated activation of the heterotrimeric G protein. Finally, kinetics analyses of Gα2βγ subunit dissociation induced by different cAMP concentrations indicate that there are two distinct rates at which the heterotrimeric G protein subunits dissociate when cells are stimulated with cAMP concentrations above 500 nM versus only one rate at lower cAMP concentrations. Quantitative modeling suggests that the kinetics profile of Gα2βγ subunit dissociation results from the presence of both uncoupled and G protein pre-coupled cAR1 that have differential affinities for cAMP and, consequently, induce G protein subunit dissociation through different rates. We suggest that these different signaling kinetic profiles may play an important role in initial chemoattractant gradient sensing. Copyright © 2018 Elsevier Inc. All rights reserved.

Biotransformation and induction: implications for toxicity, bioaccumulation and monitoring of environmental xenobiotics in fish.

PubMed Central

Kleinow, K M; Melancon, M J; Lech, J J

1987-01-01

Biotransformation of xenobiotics in fish occurs by many of the same reactions as in mammals. These reactions have been shown to affect the bioaccumulation, persistence, residue dynamics, and toxicity of select chemicals in fish. P-450-dependent monooxygenase activity of fish can be induced by polycyclic aromatic hydrocarbons, but phenobarbital-type agents induce poorly, if at all. Fish monooxygenase activity exhibits ideal temperature compensation and sex-related variation. Induction of monooxygenase activity by polycyclic aromatic hydrocarbons can result in qualitative as well as quantitative changes in the metabolic profile of a chemical. Induction can also alter toxicity. In addition, multiple P-450 isozymes have been described for several fish species. The biotransformation products of certain chemicals have been related to specific P-450 isozymes, and the formation of these products can be influenced by induction. Exposure of fish to low levels of certain environmental contaminants has resulted in induction of specific monooxygenase activities and monitoring of such activities has been suggested as a means of identifying areas of pollutant exposure in the wild. PMID:3297653

Monitoring of the mercury mining site Almadén implementing remote sensing technologies.

PubMed

Schmid, Thomas; Rico, Celia; Rodríguez-Rastrero, Manuel; José Sierra, María; Javier Díaz-Puente, Fco; Pelayo, Marta; Millán, Rocio

2013-08-01

The Almadén area in Spain has a long history of mercury mining with prolonged human-induced activities that are related to mineral extraction and metallurgical processes before the closure of the mines and a more recent post period dominated by projects that reclaim the mine dumps and tailings and recuperating the entire mining area. Furthermore, socio-economic alternatives such as crop cultivation, livestock breeding and tourism are increasing in the area. Up till now, only scattered information on these activities is available from specific studies. However, improved acquisition systems using satellite borne data in the last decades opens up new possibilities to periodically study an area of interest. Therefore, comparing the influence of these activities on the environment and monitoring their impact on the ecosystem vastly improves decision making for the public policy makers to implement appropriate land management measures and control environmental degradation. The objective of this work is to monitor environmental changes affected by human-induced activities within the Almadén area occurring before, during and after the mine closure over a period of nearly three decades. To achieve this, data from numerous sources at different spatial scales and time periods are implemented into a methodology based on advanced remote sensing techniques. This includes field spectroradiometry measurements, laboratory analyses and satellite borne data of different surface covers to detect land cover and use changes throughout the mining area. Finally, monitoring results show that the distribution of areas affected by mercury mining is rapidly diminishing since activities ceased and that rehabilitated mining areas form a new landscape. This refers to mine tailings that have been sealed and revegetated as well as an open pit mine that has been converted to an "artificial" lake surface. Implementing a methodology based on remote sensing techniques that integrate data from several sources at different scales greatly improves the regional characterization and monitoring of an area dominated by mercury mining activities. Copyright © 2013 Elsevier Inc. All rights reserved.

A pilot crossover study: effects of an intervention using an activity monitor with computerized game functions on physical activity and body composition.

PubMed

Nishiwaki, Masato; Kuriyama, Akinori; Ikegami, Yumi; Nakashima, Nana; Matsumoto, Naoyuki

2014-12-02

Wearing an activity monitor as a motivational tool and incorporating a behavior-based reward system or a computerized game element might have a synergistic effect on an increase in daily physical activity, thereby inducing body fat reduction. This pilot crossover study aimed to examine the effects of a short-term lifestyle intervention using an activity monitor with computerized game functions on physical activity and body composition. Twenty healthy volunteers (31 ± 3 years) participated in a 12-week crossover study. The participants were randomly assigned to either Group A (a 6-week game intervention followed by a 6-week normal intervention) or Group B (a 6-week normal intervention followed by a 6-week game intervention). The participants wore both a normal activity monitor (Lifecorder EX) and an activity monitor with computerized game functions (Yuuhokei) during the game intervention, whereas they only wore a normal activity monitor during the normal intervention. Before, during, and after the intervention, body composition was assessed. Significantly more daily steps were recorded for the game intervention than for the normal intervention (10,520 ± 562 versus 8,711 ± 523 steps/day, P < 0.01). The participants performed significantly more physical activity at an intensity of ≥ 3 metabolic equivalents (METs) in the game intervention than in the normal intervention (3.1 ± 0.2 versus 2.4 ± 0.2 METs · hour/day, P < 0.01). Although body mass and fat were significantly reduced in both periods (P < 0.01), the difference in body fat reduction was significantly greater in the game intervention than in the normal intervention (P < 0.05). A short-term intervention using an activity monitor with computerized game functions increases physical activity and reduces body fat more effectively than an intervention using a standard activity monitor.

PKCalpha-mediated ERK, JNK and p38 activation regulates the myogenic program in human rhabdomyosarcoma cells.

PubMed

Mauro, Annunziata; Ciccarelli, Carmela; De Cesaris, Paola; Scoglio, Arianna; Bouché, Marina; Molinaro, Mario; Aquino, Angelo; Zani, Bianca Maria

2002-09-15

We have previously suggested that PKCalpha has a role in 12-O-Tetradecanoylphorbol-13-acetate (TPA)-mediated growth arrest and myogenic differentiation in human embryonal rhabdomyosarcoma cells (RD). Here, by monitoring the signalling pathways triggered by TPA, we demonstrate that PKCalpha mediates these effects by inducing transient activation of c-Jun N-terminal protein kinases (JNKs) and sustained activation of both p38 kinase and extracellular signal-regulated kinases (ERKs) (all referred to as MAPKs). Activation of MAPKs following ectopic expression of constitutively active PKCalpha, but not its dominant-negative form, is also demonstrated. We investigated the selective contribution of MAPKs to growth arrest and myogenic differentiation by monitoring the activation of MAPK pathways, as well as by dissecting MAPK pathways using MEK1/2 inhibitor (UO126), p38 inhibitor (SB203580) and JNK and p38 agonist (anisomycin) treatments. Growth-arresting signals are triggered either by transient and sustained JNK activation (by TPA and anisomycin, respectively) or by preventing both ERK and JNK activation (UO126) and are maintained, rather than induced, by p38. We therefore suggest a key role for JNK in controlling ERK-mediated mitogenic activity. Notably, sarcomeric myosin expression is induced by both TPA and UO126 but is abrogated by the p38 inhibitor. This finding indicates a pivotal role for p38 in controlling the myogenic program. Anisomycin persistently activates p38 and JNKs but prevents myosin expression induced by TPA. In accordance with this negative role, reactivation of JNKs by anisomycin, in UO126-pre-treated cells, also prevents myosin expression. This indicates that, unlike the transient JNK activation that occurs in the TPA-mediated myogenic process, long-lasting JNK activation supports the growth-arrest state but antagonises p38-mediated myosin expression. Lastly, our results with the MEK inhibitor suggest a key role of the ERK pathway in regulating myogenic-related morphology in differentiated RD cells.

Application of the freeze-dried bioluminescent bioreporter Pseudomonas putida mt-2 KG1206 to the biomonitoring of groundwater samples from monitoring wells near gasoline leakage sites.

PubMed

Ko, Kyung-Seok; Kong, In Chul

2017-02-01

This study examined the applicability of a freeze-dried bioluminescent bioreporter, Pseudomonas putida mt-2 KG1206 (called KG1206), to the biomonitoring of groundwater samples. Samples were collected from the monitoring wells of gas station tanks or old pipeline leakage sites in Korea. In general, the freeze-dried strain in the presence of pure inducer chemicals showed low bioluminescence activity and a different activity order compared with that of the subcultured strain. The effects of KNO 3 as a bioluminescence stimulant were observed on the pure inducers and groundwater samples. The stimulation rates varied according to the type of inducers and samples, ranging from 2.2 to 20.5 times (for pure inducers) and from 1.1 to 11 times (for groundwater samples) the total bioluminescence of the control. No considerable correlations were observed between the bioluminescence intensity of the freeze-dried strain and the inducer concentrations in the samples (R 2  < 0.1344). However, samples without a high methyl tertiary butyl ether (MTBE) level and those from the gas station leakage site showed reasonable correlations with the bioluminescence activity with R 2 values of 0.3551 and 0.4131, respectively. These results highlight the potential of using freeze-dried bioluminescent bacteria as a rapid, simple, and portable tool for the preliminary biomonitoring of specific pollutants at contaminated sites.

Fracturing of porous rock induced by fluid injection

NASA Astrophysics Data System (ADS)

Stanchits, Sergei; Mayr, Sibylle; Shapiro, Serge; Dresen, Georg

2011-04-01

We monitored acoustic emission (AE) activity and brittle failure initiated by water injection into initially dry critically stressed cylindrical specimens of Flechtingen sandstone of 50 mm diameter and 105-125 mm length. Samples were first loaded in axial direction at 40-50 MPa confining pressure at dry conditions close to peak stress. Subsequently distilled water was injected either at the bottom of specimen or via a central borehole at pore pressures of 5-30 MPa. Water injection into stressed porous sandstone induced a cloud of AE events located close to the migrating water front. Water injection was monitored by periodic ultrasonic velocity measurements across the sample. Propagation of the induced cloud of AE was faster in the direction parallel to bedding than normal to it, indicating permeability anisotropy. Water injection was associated with significant AE activity demonstrating increased contribution of tensile source type. Brittle failure was accompanied by increased contribution of shear and pore collapse source types. At a critical pore pressure, a brittle fault nucleated from a cloud of induced AE events in all samples. Microstructural analysis of fractured samples shows excellent agreement between location of AE hypocenters and macroscopic faults.

Earthquakes induced by fluid injection: Implications for secure CO2 storage

NASA Astrophysics Data System (ADS)

Verdon, J.; Kendall, J. M.

2013-12-01

It is well understood that the injection of fluids into the subsurface can trigger seismic activity. Recently, the US unconventional gas boom has lead to an increase in the volumes of produced water being disposed in geological formations and a concomitant increase in triggered seismic events. This issue is especially pertinent for geologic carbon sequestration, where the injection volumes necessary to store the CO2 emissions from a typical coal-fired power station far exceed the volumes known to have triggered seismic activity. Moreover, unlike water disposal operations, where there is no strong buoyancy drive to return injected fluids to the surface, CO2 sequestration requires a sealing caprock to prevent upward CO2 migration. Induced seismic events may create or reactivate faults and fracture networks, compromising the hydraulic integrity of the caprock. Therefore, induced seismic activity at future CCS sites is of doubly significant, given both the direct seismic hazard and the risk to secure CO2 storage. With this in mind, we re-examine case histories of seismic activity induced by waste water disposal into sedimentary formations with the intention of learning lessons that can be applied to future CCS sites. In particular, we examine the spatial and temporal distributions of events to determine whether there are any rules-of-thumb that might be usefully applied when appraising and monitoring operations. We find that in all cases, at least some seismicity occurs at the depth of the injection interval, but the majority (~80% of events) occur at least 500m below the injection depth. Less than 2% of events occur more than 500m above the shallowest injection interval. This observation must be considered encouraging from a CCS perspective, where seismicity in sealing caprocks will be of greatest concern. However, without a phenomenological explanation for the relative lack of seismicity above injection depths, it cannot be guaranteed that such observations would be repeated at CCS sites. We also examine the lateral distance between induced events and injection wells. The maximum distance between wells and events will define a minimum radius of influence, a distance over which geomechanical appraisal and fault characterization studies must be carried out at future CCS sites. We find that 62% of events occur within 5km, and that 99% of events occur within 19km of injection wells. These case examples highlight the importance of seismic monitoring at future CCS sites. Of the two large-scale CCS sites to deploy microseismic arrays, both have detected induced seismic events. During 6 years of monitoring at Weyburn, ~100 events with magnitudes between -3.0 and -1.0 have been detected, while at In Salah more than 1000 events, with magnitudes as large as 1.0, have been detected during 6 months of monitoring. Combined the case examples from water disposal operations, these operations demonstrate the need for dedicated local seismic monitoring networks to be installed at future CO2 injection sites.

Monitoring the Restart of a High-Rate Wastewater Disposal Well in the Val d'Agri Oilfield (Italy)

NASA Astrophysics Data System (ADS)

De Gori, P.; Improta, L.; Moretti, M.; Colasanti, G.; Criscuoli, F.

2015-12-01

The Val d'Agri Quaternary basin in the Southern Apennine range of Italy hosts the largest inland oil field in Europe. Wastewater coming from the oil exploitation is re-injected by a high-rate disposal well into strongly fractured limestones of the hydrocarbon carbonate reservoir. Disposal activity has induced micro-seismicity since the beginning of injection in June 2006. Around 220 small magnitude events (ML < 2.3) were recorded between 2006 and 2013 by the trigger-mode monitoring local network managed by the oil company and by the National Seismic Network of Istituto Nazionale di Geofisica e Vulcanologia. The induced micro-seismicity illuminated a pre-existing high-angle fault located 1 km below the well. Since June 2006, wastewater has been re-injected with only short interruptions due acid stimulations. In January 2015 disposal activity was halted due to technical operations in the oil refinery and wastewater injection restarted after two weeks. We installed 5 short-period stations within 10 km of the disposal well to carefully monitor the re-start phase and the subsequent 3 months of disposal activity. This temporary network was complemented by stations of the National Seismic Network giving this final configuration:9 stations within 10 km of the well with the closest station 2 km apart, 13 stations within 20 km. Here we report on the preliminary analysis of the local earthquake recorded during the survey focusing on the events occurred in the injection area. The seismicity rate is compared with injection data.In spite of the dense network, we found that the rate of induced seismicity (both the number and energy of events) is very low when compared to the seismicity recorded during the first 5 years of injection activity carried out with comparable rate and pressure.

Development of Neh2-Luciferase Reporter and Its Application for High Throughput Screening and Real-Time Monitoring of Nrf2 Activators

PubMed Central

Smirnova, Natalya A.; Haskew-Layton, Renee E.; Basso, Manuela; Hushpulian, Dmitry M.; Payappilly, Jimmy B.; Speer, Rachel E.; Ahn, Young-Hoon; Rakhman, Ilay; Cole, Philip A.; Pinto, John T.; Ratan, Rajiv R.; Gazaryan, Irina G.

2011-01-01

SUMMARY The NF-E2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidant defense and detoxification. To directly monitor stabilization of Nrf2, we fused its Neh2 domain, responsible for the interaction with its nucleocytoplasmic regulator, Keap1, to firefly luciferase (Neh2-luciferase). We show that Neh2 domain is sufficient for recognition, ubiquitination, and proteasomal degradation of Neh2-luciferase fusion protein. The Neh2-luc reporter system allows direct monitoring of the adaptive response to redox stress and classification of drugs based on the time course of reporter activation. The reporter was used to screen the Spectrum library of 2000 biologically active compounds to identify activators of Nrf2. The most robust and yet nontoxic Nrf2 activators found—nordihydroguaiaretic acid, fisetin, and gedunin—induced astrocyte-dependent neuroprotection from oxidative stress via an Nrf2-dependent mechanism. PMID:21700211

Radar detection of pedestrian-induced vibrations on Michelangelo's David.

PubMed

Pieraccini, Massimiliano; Betti, Michele; Forcellini, Davide; Dei, Devis; Papi, Federico; Bartoli, Gianni; Facchini, Luca; Corazzi, Riccardo; Kovacevic, Vladimir Cerisano

2017-01-01

This paper summarizes the results of a two-day dynamic monitoring of Michelangelo's David subject to environmental loads (city traffic and pedestrian loading induced by tourists visiting the Accademia Gallery). The monitoring was carried out by a no-contact technique using an interferometric radar, whose effectiveness in measuring the resonant frequencies of structures and historic monuments has proved over the last years through numerous monitoring activities. Owing to the dynamic behavior of the measurement system (radar and tripod), an accelerometer has been installed on the radar head to filter out the movement component of the measuring instrument from the measurement of the David's displacement. Measurements were carried out in the presence and absence of visitors, to assess their influence on the dynamic behavior of the statue. A numerical model of the statue was employed to evaluate the experimental results.

Radar detection of pedestrian-induced vibrations on Michelangelo's David

PubMed Central

2017-01-01

This paper summarizes the results of a two-day dynamic monitoring of Michelangelo's David subject to environmental loads (city traffic and pedestrian loading induced by tourists visiting the Accademia Gallery). The monitoring was carried out by a no-contact technique using an interferometric radar, whose effectiveness in measuring the resonant frequencies of structures and historic monuments has proved over the last years through numerous monitoring activities. Owing to the dynamic behavior of the measurement system (radar and tripod), an accelerometer has been installed on the radar head to filter out the movement component of the measuring instrument from the measurement of the David's displacement. Measurements were carried out in the presence and absence of visitors, to assess their influence on the dynamic behavior of the statue. A numerical model of the statue was employed to evaluate the experimental results. PMID:28394932

Real-time single cell analysis of molecular mechanism of apoptosis and proliferation using FRET technique

NASA Astrophysics Data System (ADS)

Chen, Tongsheng; Xing, Da; Gao, Xuejuan; Wang, Fang

2006-09-01

Bcl-2 family proteins (such as Bid and Bak/Bax) and 14-3-3 proteins play a key role in the mitochondria-mediated cell apoptosis induced by cell death factors such as TNF-α and lower power laser irradiation (LPLI). In this report, fluorescence resonance energy transfer (FRET) has been used to study the molecular mechanism of apoptosis in living cells on a fluorescence scanning confocal microscope. Based on the genetic code technique and the green fluorescent proteins (GFPs), single-cell dynamic analysis of caspase3 activation, caspase8 activation, and PKCs activation are performed during apoptosis induced by laser irradiation in real-time. To investigate the cellular effect and mechanism of laser irradiation, human lung adenocarcinoma cells (ASTC-a-1) transfected with plasmid SCAT3 (pSCAT3)/ CKAR FRET reporter, were irradiated and monitored noninvasively with both FRET imaging. Our results show that high fluence lower power laser irradiation (HFLPLI) can induce an increase of caspase3 activation and a decrease of PKCs activation, and that LPLI induces the ASTC-a-1 cell proliferation by specifically activating PKCs.

Detection of receptor ligands by monitoring selective stabilization of a Renilla luciferase-tagged, constitutively active mutant, G-protein-coupled receptor

PubMed Central

Ramsay, Douglas; Bevan, Nicola; Rees, Stephen; Milligan, Graeme

2001-01-01

The wild-type β2-adrenoceptor and a constitutively active mutant of this receptor were C-terminally tagged with luciferase from the sea pansy Renilla reniformis. C-terminal addition of Renilla luciferase did not substantially alter the levels of expression of either form of the receptor, the elevated constitutive activity of the mutant β2-adrenoceptor nor the capacity of isoprenaline to elevate cyclic AMP levels in intact cells expressing these constructs. Treatment of cells expressing constitutively active mutant β2-adrenoceptor-Renilla luciferase with antagonist/inverse agonist ligands resulted in upregulation of levels of this polypeptide which could be monitored by the elevated luciferase activity. The pEC50 for ligand-induced luciferase upregulation and ligand affinity to bind the receptor were highly correlated. Similar upregulation could be observed following sustained treatment with agonist ligands. These effects were only observed at a constitutively active mutant of the β2-adrenoceptor. Co-expression of the wild-type β2-adrenoceptor C-terminally tagged with the luciferase from Photinus pyralis did not result in ligand-induced upregulation of the levels of activity of this luciferase. Co-expression of the constitutively active mutant β2-adrenoceptor-Renilla luciferase and an equivalent mutant of the α1b-adrenoceptor C-terminally tagged with green fluorescent protein allowed pharmacological selectivity of adrenoceptor antagonists to be demonstrated. This approach offers a sensitive and convenient means, which is amenable to high throughput analysis, to monitor ligand binding to a constitutively active mutant receptor. As no prior knowledge of receptor ligands is required this approach may be suitable to identify ligands at orphan G protein-coupled receptors. PMID:11350868

Embedded and conventional ultrasonic sensors for monitoring acoustic emission during thermal fatigue

NASA Astrophysics Data System (ADS)

Trujillo, Blaine; Zagrai, Andrei

2016-04-01

Acoustic emission is widely used for monitoring pressure vessels, pipes, critical infrastructure, as well as land, sea and air vehicles. It is one of dominant approaches to explore material degradation under fatigue and events leading to material fracture. Addressing a recent interest in structural health monitoring of space vehicles, a need has emerged to evaluate material deterioration due to thermal fatigue during spacecraft atmospheric reentry. Thermal fatigue experiments were conducted, in which aluminum plates were subjected to localized heating and acoustic emission was monitoring by embedded and conventional acoustic emission sensors positioned at various distances from a heat source. At the same time, surface temperature of aluminum plates was monitored using an IR camera. Acoustic emission counts collected by embedded sensors were compared to counts measured with conventional acoustic emission sensors. Both types of sensors show noticeable increase of acoustic emission activity as localized heating source was applied to aluminum plates. Experimental data demonstrate correlation between temperature increase on the surface of the plates and increase in measured acoustic emission activity. It is concluded that under particular conditions, embedded piezoelectric wafer active sensors can be used for acoustic emission monitoring of thermally-induced structural degradation.

Decoy receptor 3 suppresses RANKL-induced osteoclastogenesis via down-regulating NFATc1 and enhancing cell apoptosis.

PubMed

Cheng, Chia-Pi; Sheu, Ming-Jen; Sytwu, Huey-Kang; Chang, Deh-Ming

2013-04-01

Decoy receptor 3 (DCR3) has been known to modulate immune functions of monocyte or macrophage. In the present study, we investigated the mechanism and the effect of DCR3 on RANK ligand (RANKL)-induced osteoclastogenesis. We treated cells with DCR3 in RANKL-induced osteoclastogenesis to monitor osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining. Osteoclast activity was assessed by pit formation assay. The mechanism of inhibition was studied by biochemical analysis such as RT-PCR and immunoblotting. In addition, cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis and apoptosis signalling were evaluated by immunoblotting and using flow cytometry. DCR3 inhibited RANKL-induced TRAP(+) multinucleated cells and inhibited RANKL-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) nuclear translocation in RAW264.7 cells. Also, DCR3 significantly inhibited the bone-resorbing activity of mature osteoclasts. Moreover, DCR3 enhanced RANKL-induced cell apoptosis and enhanced RANKL-induced Fas ligand expression. The mechanisms were mediated via the intrinsic cytochrome c and activated caspase 9 apoptosis pathway. We postulated that the inhibitory activity of DCR3 on osteoclastogenesis occurs via down-regulation of RANKL-induced NFATc1 expression and induction of cell apoptosis. Our results postulated DCR3 as a possible new remedy against inflammatory bone destruction.

A synthetic compound that potentiates bone morphogenetic protein-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype

PubMed Central

Kato, Satoshi; Tomita, Katsuro; Titus, Louisa; Boden, Scott D.

2011-01-01

There is an urgent need to develop methods that lower costs of using recombinant human bone morphogenetic proteins (BMPs) to promote bone induction. In this study, we demonstrate the osteogenic effect of a low-molecular weight compound, SVAK-12, that potentiated the effects of BMP-2 in inducing transdifferentiation of C2C12 myoblasts into the osteoblastic phenotype. Here, we report a specific compound, SVAK-12, which was selected based on in silico screenings of small-molecule databases using the homology modeled interaction motif of Smurf1-WW2 domain. The enhancement of BMP-2 activity by SVAK-12 was characterized by evaluating a BMP-specific reporter activity and by monitoring the BMP-2-induced expression of mRNA for osteocalcin and alkaline phosphatase (ALP), which are widely accepted marker genes of osteoblast differentiation. Finally, we confirmed these results by also measuring the enhancement of BMP-2-induced activity of ALP. Smurf1 is an E3 ligase that targets osteogenic Smads for ubiquitin-mediated proteasomal degradation. Smurf1 is an interesting potential target to enhance bone formation based on the positive effects on bone of proteins that block Smurf1-binding to Smad targets or in Smurf1−/− knockout mice. Since Smads bind Smurf1 via its WW2 domain, we performed in silico screening to identify compounds that might interact with the Smurf1-WW2 domain. We recently reported the activity of a compound, SVAK-3. However, SVAK-3, while exhibiting BMP-potentiating activity, was not stable and thus warranted a new search for a more stable and efficacious compound among a selected group of candidates. In addition to being more stable, SVAK-12 exhibited a dose-dependent activity in inducing osteoblastic differentiation of myoblastic C2C12 cells even when multiple markers of the osteoblastic phenotype were parallelly monitored. PMID:21110071

A synthetic compound that potentiates bone morphogenetic protein-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype.

PubMed

Kato, Satoshi; Sangadala, Sreedhara; Tomita, Katsuro; Titus, Louisa; Boden, Scott D

2011-03-01

There is an urgent need to develop methods that lower costs of using recombinant human bone morphogenetic proteins (BMPs) to promote bone induction. In this study, we demonstrate the osteogenic effect of a low-molecular weight compound, SVAK-12, that potentiated the effects of BMP-2 in inducing transdifferentiation of C2C12 myoblasts into the osteoblastic phenotype. Here, we report a specific compound, SVAK-12, which was selected based on in silico screenings of small-molecule databases using the homology modeled interaction motif of Smurf1-WW2 domain. The enhancement of BMP-2 activity by SVAK-12 was characterized by evaluating a BMP-specific reporter activity and by monitoring the BMP-2-induced expression of mRNA for osteocalcin and alkaline phosphatase (ALP), which are widely accepted marker genes of osteoblast differentiation. Finally, we confirmed these results by also measuring the enhancement of BMP-2-induced activity of ALP. Smurf1 is an E3 ligase that targets osteogenic Smads for ubiquitin-mediated proteasomal degradation. Smurf1 is an interesting potential target to enhance bone formation based on the positive effects on bone of proteins that block Smurf1-binding to Smad targets or in Smurf1-/- knockout mice. Since Smads bind Smurf1 via its WW2 domain, we performed in silico screening to identify compounds that might interact with the Smurf1-WW2 domain. We recently reported the activity of a compound, SVAK-3. However, SVAK-3, while exhibiting BMP-potentiating activity, was not stable and thus warranted a new search for a more stable and efficacious compound among a selected group of candidates. In addition to being more stable, SVAK-12 exhibited a dose-dependent activity in inducing osteoblastic differentiation of myoblastic C2C12 cells even when multiple markers of the osteoblastic phenotype were parallelly monitored.

A transgenic zebrafish model for monitoring xbp1 splicing and endoplasmic reticulum stress in vivo.

PubMed

Li, Junling; Chen, Zhiliang; Gao, Lian-Yong; Colorni, Angelo; Ucko, Michal; Fang, Shengyun; Du, Shao Jun

2015-08-01

Accumulation of misfolded or unfolded proteins in the endoplasmic reticulum (ER) triggers ER stress that initiates unfolded protein response (UPR). XBP1 is a transcription factor that mediates one of the key signaling pathways of UPR to cope with ER stress through regulating gene expression. Activation of XBP1 involves an unconventional mRNA splicing catalyzed by IRE1 endonuclease that removes an internal 26 nucleotides from xbp1 mRNA transcripts in the cytoplasm. Researchers have taken advantage of this unique activation mechanism to monitor XBP1 activation, thereby UPR, in cell culture and transgenic models. Here we report a Tg(ef1α:xbp1δ-gfp) transgenic zebrafish line to monitor XBP1 activation using GFP as a reporter especially in zebrafish oocytes and developing embryos. The Tg(ef1α:xbp1δ-gfp) transgene was constructed using part of the zebrafish xbp1 cDNA containing the splicing element. ER stress induced splicing results in the cDNA encoding a GFP-tagged partial XBP1 without the transactivation activation domain (XBP1Δ-GFP). The results showed that xbp1 transcripts mainly exist as the spliced active isoform in unfertilized oocytes and zebrafish embryos prior to zygotic gene activation at 3 hours post fertilization. A strong GFP expression was observed in unfertilized oocytes, eyes, brain and skeletal muscle in addition to a weak expression in the hatching gland. Incubation of transgenic zebrafish embryos with (dithiothreitol) DTT significantly induced XBP1Δ-GFP expression. Collectively, these studies unveil the presence of maternal xbp1 splicing in zebrafish oocytes, fertilized eggs and early stage embryos. The Tg(ef1α:xbp1δ-gfp) transgenic zebrafish provides a useful model for in vivo monitoring xbp1 splicing during development and under ER stress conditions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The effects of octanol on penicillin induced epileptiform activity in rats: an in vivo study.

PubMed

Bostanci, M Omer; Bağirici, Faruk

2006-10-01

The common features of all types of epilepsy are the synchronized and uncontrolled discharges of nerve cell assemblies. The reason for the pathologically synchronized discharges of the neuron is not exactly known yet. Recent reports claim that gap junctions have a critical role in neuronal synchronization. The present study was planned to investigate the effects of octanol, a gap junction blocker, on penicillin-induced experimental epilepsy. Permanent screw electrodes allowing EEG monitoring from conscious animals and permanent cannula providing the administration of the substances to the brain ventricle were placed into the cranium of rats under general anesthesia. After the postoperative recovery period, epileptiform activity was generated by injecting 300 IU crystallized penicillin through the ventricular cannula. When epileptiform activity, monitored from a digital recording system, reached at its maximum intensity, octanol was applied in the same way as penicillin administered. Application of octanol caused an inhibition in the epileptiform activity. Vehicle solution alone did not affect the epileptiform activity. Results of this study suggest that the blockade of electrical synapses may contribute to the prevention and amelioration of epileptic activity. Production of gap junction blockers selective for connexin types is needed. Further studies on the differential roles of gap junctions on certain epileptiform activities are required.

Activation mechanism of melB tyrosinase from Aspergillus oryzae by acidic treatment.

PubMed

Fujieda, Nobutaka; Murata, Michiaki; Yabuta, Shintaro; Ikeda, Takuya; Shimokawa, Chizu; Nakamura, Yukihiro; Hata, Yoji; Itoh, Shinobu

2013-01-01

The pro form of recombinant tyrosinase from Aspergillus oryzae (melB) shows no catalytic activity, but acid treatment (around pH 3.5) of protyrosinase activates it to induce tyrosinase activity. Circular dichroism spectra, gel filtration analysis, and colorimetric assay have indicated that acid treatment around pH 3.5 induced the disruption of the conformation of the C-terminal domain covering the enzyme active site. These structural changes induced by the acid treatment may open the entrance to the enzyme active site for substrate incorporation. To compare the mechanism of hydroxylation by the acid-treated tyrosinase with that by trypsin-treated tyrosinase, a detailed steady-state kinetic analysis of the phenolase activity was performed by monitoring the O(2)-consumption rate using a Clark-type oxygen electrode. The results clearly show that the phenolase activity (phenol hydroxylation) of the activated tyrosinase involves an electrophilic aromatic substitution mechanism as in the case of mushroom tyrosinase (Yamazaki and Itoh in J. Am. Chem. Soc. 125:13034-13035, 2003) and activated hemocyanin with urea (Morioka et al. in J. Am. Chem. Soc. 128:6788-6789, 2006).

Long-term microfluidic glucose and lactate monitoring in hepatic cell culture

PubMed Central

Prill, Sebastian; Jaeger, Magnus S.; Duschl, Claus

2014-01-01

Monitoring cellular bioenergetic pathways provides the basis for a detailed understanding of the physiological state of a cell culture. Therefore, it is widely used as a tool amongst others in the field of in vitro toxicology. The resulting metabolic information allows for performing in vitro toxicology assays for assessing drug-induced toxicity. In this study, we demonstrate the value of a microsystem for the fully automated detection of drug-induced changes in cellular viability by continuous monitoring of the metabolic activity over several days. To this end, glucose consumption and lactate secretion of a hepatic tumor cell line were continuously measured using microfluidically addressed electrochemical sensors. Adapting enzyme-based electrochemical flat-plate sensors, originally designed for human whole-blood samples, to their use with cell culture medium supersedes the common manual and laborious colorimetric assays and off-line operated external measurement systems. The cells were exposed to different concentrations of the mitochondrial inhibitor rotenone and the cellular response was analyzed by detecting changes in the rates of the glucose and lactate metabolism. Thus, the system provides real-time information on drug-induced liver injury in vitro. PMID:24926387

Suspected adverse reactions to contrast media in Campania Region (Italy): results from 14 years of post-marketing surveillance.

PubMed

Sessa, Maurizio; Rossi, Claudia; Mascolo, Annamaria; Grassi, Enrico; Fiorentino, Sonia; Scavone, Cristina; Reginelli, Alfonso; Rotondo, Antonio; Sportiello, Liberata

2015-01-01

During the last years in Italy, contrast media (CM) use increased. An increase of monitoring activities on CM-induced adverse drug reaction (ADR) is necessary, also in our regional territory. The main aim of this study was to give a preliminary evaluation of all Spontaneous Reports of ADRs (SRA) attributed to CM sent to Campania Pharmacovigilance Regional Center (CRFVC) from 01 January 2001 to 31 October 2014. For each SRA we evaluated: frequency and source, ADRs onset (time to event, seriousness and outcome), socio-demographic characteristics and risk factors of cases, the most reported CM (checking for pharmacodynamic and pharmacokinetic interactions). A total of 111 SRA were sent to CRFVC; specialist in radiology was the main source of reports. Ninety-seven SRA (87.3%) were referable to hypersensitivity reactions. Thirty-four SRA (30.6%) reported serious ADRs. The most reported CM were iopamidol, gadobenic acid and gadoteric acid. We identified two SRA induced by pharmacokinetic and/or pharmacodynamic interactions. During 14 years of post-marketing surveillance, only few SRA concerning CM-induced ADRs were sent to CRFVC probably due to underreporting. We aim to improve monitoring activity on CM-induced ADRs especially in hospitals. Most reported ADR and CM were in line with current body of literature.

Hyperventilation revisited: physiological effects and efficacy on focal seizure activation in the era of video-EEG monitoring.

PubMed

Guaranha, Mirian S B; Garzon, Eliana; Buchpiguel, Carlos A; Tazima, Sérgio; Yacubian, Elza M T; Sakamoto, Américo C

2005-01-01

Hyperventilation is an activation method that provokes physiological slowing of brain rhythms, interictal discharges, and seizures, especially in generalized idiopathic epilepsies. In this study we assessed its effectiveness in inducing focal seizures during video-EEG monitoring. We analyzed the effects of hyperventilation (HV) during video-EEG monitoring (video-EEG) of patients with medically intractable focal epilepsies. We excluded children younger than 10 years, mentally retarded patients, and individuals with frequent seizures. We analyzed 97 patients; 24 had positive seizure activation (PSA), and 73 had negative seizure activation (NSA). No differences were found between groups regarding sex, age, age at epilepsy onset, duration of epilepsy, frequency of seizures, and etiology. Temporal lobe epilepsies were significantly more activated than frontal lobe epilepsies. Spontaneous and activated seizures did not differ in terms of their clinical characteristics, and the activation did not affect the performance of ictal single-photon emission computed tomography (SPECT). HV is a safe and effective method of seizure activation during monitoring. It does not modify any of the characteristics of the seizures and allows the obtaining of valuable ictal SPECTs. This observation is clinically relevant and suggests the effectiveness and the potential of HV in shortening the presurgical evaluation, especially of temporal lobe epilepsy patients, consequently reducing its costs and increasing the number of candidates for epilepsy surgery.

Trend of telomerase activity change during human iPSC self-renewal and differentiation revealed by a quartz crystal microbalance based assay

NASA Astrophysics Data System (ADS)

Zhou, Yitian; Zhou, Ping; Xin, Yinqiang; Wang, Jie; Zhu, Zhiqiang; Hu, Ji; Wei, Shicheng; Ma, Hongwei

2014-11-01

Telomerase plays an important role in governing the life span of cells for its capacity to extend telomeres. As high activity of telomerase has been found in stem cells and cancer cells specifically, various methods have been developed for the evaluation of telomerase activity. To overcome the time-consuming procedures and complicated manipulations of existing methods, we developed a novel method named Telomeric Repeat Elongation Assay based on Quartz crystal microbalance (TREAQ) to monitor telomerase activity during the self-renewal and differentiation of human induced pluripotent stem cells (hiPSCs). TREAQ results indicated hiPSCs possess invariable telomerase activity for 11 passages on Matrigel and a steady decline of telomerase activity when differentiated for different periods, which is confirmed with existing golden standard method. The pluripotency of hiPSCs during differentiation could be estimated through monitoring telomerase activity and compared with the expression levels of markers of pluripotency gene via quantitative real time PCR. Regular assessment for factors associated with pluripotency or stemness was expensive and requires excessive sample consuming, thus TREAQ could be a promising alternative technology for routine monitoring of telomerase activity and estimate the pluripotency of stem cells.

Delayed de-induction of CYP2C9 compared to CYP3A after discontinuation of rifampicin: Report of two cases
.

PubMed

Shibata, Soichi; Takahashi, Harumi; Baba, Akiyasu; Takeshita, Kei; Atsuda, Koichiro; Matsubara, Hajime; Echizen, Hirotoshi

2017-05-01

Timely dose reduction of concomitant medications is important after withdrawal of rifampicin, a CYP inducer. However, little is known about the differences in the time course of deinduction for various CYP isoforms. To clarify the time courses of deinduction of CYP2C9 and -CYP3A activities after rifampicin withdrawal, we monitored these enzyme activities in 2 patients over time after discontinuing rifampicin. Two patients (aged 70 and 80 years) received warfarin and rifampicin for anticoagulation and antituberculosis therapy, respectively. Warfarin doses were increased due to rifampicin-induced CYP activity. Upon completion of antituberculosis therapy, rifampicin was discontinued and warfarin doses were titrated downward according to prothrombin time. We monitored CYP2C9 and CYP3A activities over their clinical courses by measuring the metabolic clearance of S-warfarin to S-7-hydroxywarfarin and that of cortisol to 6β-hydroxycortisol, respectively. In both patients, the time courses of CYP2C9 deinduction appeared to be delayed compared to CYP3A. Our findings suggest that a uniform dose reduction protocol for drugs metabolized by different CYP isoforms may be unsafe after rifampicin withdrawal.
.

Aquifers as indicators of volcanic unrest - models of hydrological responses to magmatic activity and their geophysical signals

NASA Astrophysics Data System (ADS)

Strehlow, Karen; Gottsmann, Jo

2014-05-01

Aquifers respond to and modify the surface expressions of magmatic activity, and they can also become agents of unrest themselves. Therefore, monitoring the hydrology can provide a valuable window into subsurface processes in volcanic areas. Interpretations of unrest signals as groundwater responses to changes in the magmatic system can be found for many volcanoes. Changes in temperature and strain conditions, seismic excitation or the injection of magmatic fluids into hydrothermal systems are just a few of the proposed processes induced by magmatic activity that affect the local hydrology. Aquifer responses are described to include changes in water table levels, changes in temperature or composition of hydrothermal waters and pore pressure-induced ground deformation. We can observe these effects at the surface via geophysical and geochemical signals. To fully to utilise these indicators as monitoring and forecasting tools, however, it is necessary to improve our still poor understanding of the ongoing mechanisms in the interactions of hydrological and magmatic systems. An extensive literature research provided an overview on reported effects, which we investigate in detail using numerical modelling. The hydrogeophysical study uses finite element analysis to quantitatively test proposed mechanisms of aquifer excitation and the resultant geophysical signals. We present a set of generic models for two typical volcanic landforms - a stratovolcano and a caldera - that simulate the interaction between deeper magmatic systems with shallow-seated aquifers, focusing on strain and temperature effects. They predict pore pressure induced hydraulic head changes in the aquifer as well as changing groundwater temperatures and strain induced fluid migration. Volcano observatories can track these hydrological effects for example with potential field investigations or the monitoring of wells. The models allow us to explore the parameter space, contributing to a better understanding of the coupling of these two highly complex systems. Our results provide further insight into the subsurface processes at volcanic systems and will aid the evaluation of unrest signals with potential for improved eruption forecasting.

Monitoring induced seismicity from underground gas storage: first steps in Italy

NASA Astrophysics Data System (ADS)

Mucciarelli, Marco; Priolo, Enrico

2013-04-01

The supply of natural gas and its storage are focal points of the Italian politics of energy production and will have increasing importance in the coming years. About a dozen reservoirs are currently in use and fifteen are in development or awaiting approval. Some of these are found in the vicinity of geological structures that are seismically active. The assessment of seismic hazard (both for natural background and induced seismicity) for a geological gas storage facility has a number of unconventional aspects that must be recognized and traced in a clear, ordered way and using guidelines and rules that leave less room as possible for interpretation by the individual applicant / verification body. Similarly, for control and monitoring there are not clearly defined procedures or standard instrumentation, let alone tools for analysing and processing data. Finally, governmental organizations in charge of permission grants and operative control tend to have appropriate scientific knowledge only in certain areas and not in others (e.g. the seismic one), and the establishment of an independent multidisciplinary inspection body appears desirable. The project StoHaz (https://sites.google.com/site/s2stohaz/home) aims to initiate a series of actions to overcome these deficiencies and allow to define procedures and standards for the seismic hazard assessment and control of the activities of natural gas storage in underground reservoirs. OGS will take advantage of the experience gained with the design, installation and maintenance of the seismic network monitoring the Collalto reservoir, at the moment the only example in Italy of a public research institution monitoring independently the activities of a private gas storage company.

Temperature and current coefficients of lasing wavelength in tunable diode laser spectroscopy.

PubMed

Fukuda, M; Mishima, T; Nakayama, N; Masuda, T

2010-08-01

The factors determining temperature and current coefficients of lasing wavelength are investigated and discussed under monitoring CO(2)-gas absorption spectra. The diffusion rate of Joule heating at the active layer to the surrounding region is observed by monitoring the change in the junction voltage, which is a function of temperature and the wavelength (frequency) deviation under sinusoidal current modulation. Based on the experimental results, the time interval of monitoring the wavelength after changing the ambient temperature or injected current (scanning rate) has to be constant at least to eliminate the monitoring error induced by the deviation of lasing wavelength, though the temperature and current coefficients of lasing wavelength differ with the rate.

Regional Monitoring Plan for the Detection of Allergens in Food from Campania Region. First Year Monitoring Results

PubMed Central

Biondi, Loredana; Pellicanò, Roberta; Caligiuri, Vincenzo; Nava, Donatella

2014-01-01

Food allergens are substances able to induce an abnormal immunological response in sensitive individuals. The presence of allergens in food must be reported in tables (Directive 2003/89/EC). In this study we report the data of a monitoring plan carried out in the Campania Region during the 2012 for the detection of allergens (ovoalbumine and β-lattoglobulin) in food of different origin. The analisys were performed by means of ELISA assays. The percentage of analyzes with the presence of allegens not declared on the label is 4.3%, out of a total of 208 analyzes. It is therefore important to continue monitoring activities by the competent Authorities. PMID:27800313

Relationship between carbachol hyperstimulation-induced pancreatic intracellular trypsinogen and NF-kappa B activation in rats in vitro.

PubMed

Jiang, Chunfang; Zheng, Hai; Liu, Sunan; Fang, Kaifeng

2008-02-01

The relationship between intracellular trypsinogen activation and NF-kappa B activation in rat pancreatic acinar cells induced by M3 cholinergic receptor agonist (carbachol) hyperstimulation was studied. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, the active protease inhibitor (pefabloc) and NF-kappa B inhibitor (PDTC) in vitro. Intracellular trypsin activity was measured by using a fluorogenic substrate. The activity of NF-kappa B was monitored by using electrophoretic mobility shift assay. The results showed that after pretreatment with 2 mmol/L pefabloc, the activities of trypsin and NF-kappa B in pancreatic acinar cells treated with high concentrations of carbachol (10(-3) mol/L) in vitro was significantly decreased as compared with control group (P<0.01). The addition of 10(-2) mol/L PDTC resulted in a significant decrease of NF-kappa B activities in pancreatic acinar cells after treated with high concentrations of carbachol (10(-3) mol/L) in vitro, but the intracellular trypsinogen activity was not obviously inhibited (P>0.05). It was concluded that intracellular trypsinogen activation is likely involved in the regulation of high concentrations of carbachol-induced NF-kappa B activation in pancreatic acinar cells in vitro. NF-kappa B activation is likely not necessary for high concentrations of carbachol-induced trypsinogen activation in pancreatic acinar cells in vitro.

Active sensing of fatigue damage using embedded ultrasonics

NASA Astrophysics Data System (ADS)

Zagrai, Andrei; Kruse, Walter A.; Gigineishvili, Vlasi

2009-03-01

Embedded ultrasonics has demonstrated considerable utility in structural health monitoring of aeronautical vehicle. This active sensing approach has been widely used to detect and monitor cracks, delaminations, and disbonds in a broad spectrum of metallic and composite structures. However, application of the embedded ultrasonics for active sensing of incipient damage before fracture has received limited attention. The aim of this study was to investigate the suitability of embedded ultrasonics and nonlinear acoustic signatures for monitoring pre-crack fatigue damage in aerospace structural material. A harmonic load was applied to structural specimens in order to induce fatigue damage accumulation and growth. Specimens of simple geometry were considered and piezoelectric active sensors were employed for generation and reception of elastic waves. The elastic wave signatures were analyzed in the frequency domain using nonlinear impedance and nonlinear resonance methods. A relationship between fatigue severity and linear as well as nonlinear acoustic signatures was investigated and considered in the damage classification procedure. Practical aspects of the active sensing of the fatigue damage before fracture were discussed and prospective avenues for future research were suggested.

Photo-triggered fluorescent theranostic prodrugs as DNA alkylating agents for mechlorethamine release and spatiotemporal monitoring.

PubMed

Cao, Yanting; Pan, Rong; Xuan, Weimin; Wei, Yongyi; Liu, Kejian; Zhou, Jiahong; Wang, Wei

2015-06-28

We describe a new theranostic strategy for selective delivery and spatiotemporal monitoring of mechlorethamine, a DNA alkylating agent. A photo-responsive prodrug is designed and composed of a photolabile o-nitrophenylethyl group, a DNA alkylating mechlorethamine drug and a coumarin fluorophore. Masking of the "N" in mechlorethamine in a positively charged state in the prodrug renders it inactive, non-toxic, selective and non-fluorescent. Indeed, the stable prodrug shows negligible cytotoxicity towards normal cells with and without UV activation and is completely non-fluorescent. However, upon photo-irradiation, the active mechlorethamine is released and induces efficient DNA cross-links, accompanied by a strong fluorescence enhancement (152 fold). Furthermore, DNA cross-linking activity from the release can be transformed into anticancer activity observed in in vitro studies of tumor cells. Importantly, the drug release progress and the movement can be conveniently monitored by fluorescence spectroscopy. The mechanistic study proves that the DNA cross-linking activity is mainly due to the release of DNA alkylating mechlorethamine. Altogether, the studies show the power of the theranostic strategy for efficient therapy in cancer treatment.

Actin cytoskeleton and exocytosis in rat melanotrophs.

PubMed

Chowdhury, Helana H; Popoff, Michel R; Zorec, Robert

2000-01-01

We monitored secretory activity of single rat melanotrophs by the patch-clamp membrane capacitance measurements (C m ). Secretory activity was stimulated by cytosol dialysis with a patch-pipette solution containing 1μM [Ca 2+ ] i . Actin cytoskeleton was disaggregated by pretreating cells with Clostridium spiroforme toxin, which specifically ADP-ribosylates cellular actin. The extent of cytoskeleton disaggregation was monitored by phalloidin immunostaining. The maximal rate of secretion increases two folds in toxin-treated cells in comparison to controls, whereas the extent of calcium-induced secretory response was similar to that obtained in the non-treated cells. The results show that the subcortical actin network attenuates the rate of secretory activity, which we interpret to reflect a barrier function of cytoskeleton for exocytosis.

Actin cytoskeleton and exocytosis in rat melanotrophs.

PubMed

Chowdhury, H H; Popoff, M R; Zorec, R

2000-01-01

We monitored secretory activity of single rat melanotrophs by the patch-clamp membrane capacitance measurements (Cm). Secretory activity was stimulated by cytosol dialysis with a patch-pipette solution containing 1 microM [Ca2+]i. Actin cytoskeleton was disaggregated by pretreating cells with Clostridium spiroforme toxin, which specifically ADP-ribosylates cellular actin. The extent of cytoskeleton disaggregation was monitored by phalloidin immunostaining. The maximal rate of secretion increases two folds in toxin-treated cells in comparison to controls, whereas the extent of calcium-induced secretory response was similar to that obtained in the non-treated cells. The results show that the subcortical actin network attenuates the rate of secretory activity, which we interpret to reflect a barrier function of cytoskeleton for exocytosis.

Real-time monitoring of inflammation status in 3T3-L1 adipocytes possessing a secretory Gaussia luciferase gene under the control of nuclear factor-kappa B response element

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagasaki, Haruka; Yoshimura, Takeshi; Aoki, Naohito, E-mail: n-aoki@bio.mie-u.ac.jp

2012-04-13

Highlights: Black-Right-Pointing-Pointer Inflammation status in adipocytes can be monitored by the new assay system. Black-Right-Pointing-Pointer Only an aliquot of conditioned medium is required without cell lysis. Black-Right-Pointing-Pointer Inflammation-attenuating compounds can be screened more conveniently. -- Abstract: We have established 3T3-L1 cells possessing a secretory Gaussia luciferase (GLuc) gene under the control of nuclear factor-kappa B (NF-{kappa}B) response element. The 3T3-L1 cells named 3T3-L1-NF-{kappa}B-RE-GLuc could differentiate into adipocyte as comparably as parental 3T3-L1 cells. Inflammatory cytokines such as tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-1{beta} induced GLuc secretion of 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes in a concentration- and time-dependent manner. GLuc secretion of 3T3-L1-NF-{kappa}B-RE-GLucmore » adipocytes was also induced when cultured with RAW264.7 macrophages and was dramatically enhanced by lipopolysaccharide (LPS)-activated macrophages. An NF-{kappa}B activation inhibitor BAY-11-7085 and an antioxidant N-acetyl cysteine significantly suppressed GLuc secretion induced by macrophages. Finally, we found that rosemary-derived carnosic acid strongly suppressed GLuc secretion induced by macrophages and on the contrary up-regulated adiponectin secretion. Collectively, by using 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes, inflammation status can be monitored in real time and inflammation-attenuating compounds can be screened more conveniently.« less

Interpreting Reservoir Microseismicity Detected During CO2 Injection at the Aneth Oil Field

NASA Astrophysics Data System (ADS)

Rutledge, J. T.

2009-12-01

Microseismic monitoring is expected to be a useful tool in CO2 sequestration projects for mapping pressure fronts and detecting fault activation and potential leakage paths. Downhole microseismic monitoring and several other techniques are being tested for their efficacy in tracking movement and containment of CO2 injected at the Aneth oil field located in San Juan County, Utah. The Southwest Regional Partnership on CO2 Sequestration is conducting the monitoring activities in collaboration with Resolute Natural Resources Company, under the support of the U.S. Department of Energy’s National Energy Technology Laboratory. The CO2 injection at Aneth is associated with a field-wide enhanced oil recovery operation following decades of pressure maintenance and oil recovery by water-flood injection. A 60-level geophone string was cemented into a monitoring well equipped with both 3-component and vertical component geophones spanning from 800 to 1700 m depth. The top of the oil reservoir in the study area is at approximately 1730 m depth. Over the first year of monitoring, approximately 3800 microearthquakes have been detected within about 3 km of the geophone string. The Aneth reservoir events are relatively large with magnitudes ranging from approximately -1 to 1. For comparison, reservoir seismicity induced during hydraulic fracturing treatments typically result in events with magnitudes <-1, unless pre-existing faults are pressurized by the treatments. The Aneth events delineate two NW-SE oriented fracture zones located on opposite flanks of the reservoir. Injection activity is fairly uniform over the entire field area, and the microseismicity does not correlate either temporally or spatially with any anomalous changes in injection or production activities near the source locations. Because the activity is fairly isolated and relatively energetic, I speculate that the seismicity may be due to critically stressed structures driven by longer-term production- and/or injection-induced stress changes. Ongoing analysis includes extracting precise arrival time to improve relative source locations and looking for correlations of event occurrence and moment release with field-wide rates of injection and production.

Relationships among the behavioral, noradrenergic, and pituitary–adrenal responses to interleukin-1 and the effects of indomethacin

PubMed Central

Wieczorek, Marek; Dunn, Adrian J.

2007-01-01

Peripheral administration of interleukin-1 (IL-1) is known to activate the hypothalamo–pituitary–adrenal axis (HPA axis) and brain noradrenergic systems. We studied the relationship between these responses using in vivo microdialysis to assess the release of hypothalamic norepinephrine (NE), while simultaneously sampling blood for ACTH and corticosterone, and monitoring body temperature and behavior in freely moving rats. Rats were implanted with microdialysis probes in the medial hypothalamus, with intravenous catheters, and with telethermometers in the abdomen. Each rat was injected with saline and IL-1β (1 μg ip) in random order, monitoring microdialysate NE, body temperature and plasma ACTH and corticosterone for 2–4 h after injection. Saline injections were followed by transient increases in microdialysate NE and in plasma ACTH and corticosterone. IL-1β injections resulted in prolonged elevations of microdialysate NE, as well as plasma ACTH and corticosterone, and body temperature. IL-1β also induced shivering and a prolonged depression of locomotor activity. Pretreatment with indomethacin (10 mg/kg sc) prevented the IL-1β-induced increases in body temperature and the apparent increase in hypothalamic NE release, but only attenuated the IL-1β-induced shivering and the increase in plasma ACTH. The results indicate a close temporal relationship between the release of NE and HPA axis activation. Such a relationship is also supported by the similar effects of indomethacin pretreatment on NE and ACTH. The shivering is likely involved in the increase in body temperature, but indomethacin only attenuated the shivering while it blocked the fever. However, the effects of indomethacin clearly indicate that neither the increase in body temperature nor the increase in hypothalamic NE release was essential for HPA axis activation. These results suggest that hypothalamic NE is involved in the IL-1-induced HPA axis activation, but that this is not the only mechanism by which the HPA axis is activated by intraperitoneally injected IL-1. PMID:16330180

Relationships among the behavioral, noradrenergic, and pituitary-adrenal responses to interleukin-1 and the effects of indomethacin.

PubMed

Wieczorek, Marek; Dunn, Adrian J

2006-09-01

Peripheral administration of interleukin-1 (IL-1) is known to activate the hypothalamo-pituitary-adrenal axis (HPA axis) and brain noradrenergic systems. We studied the relationship between these responses using in vivo microdialysis to assess the release of hypothalamic norepinephrine (NE), while simultaneously sampling blood for ACTH and corticosterone, and monitoring body temperature and behavior in freely moving rats. Rats were implanted with microdialysis probes in the medial hypothalamus, with intravenous catheters, and with telethermometers in the abdomen. Each rat was injected with saline and IL-1beta (1 microg ip) in random order, monitoring microdialysate NE, body temperature and plasma ACTH and corticosterone for 2-4 h after injection. Saline injections were followed by transient increases in microdialysate NE and in plasma ACTH and corticosterone. IL-1beta injections resulted in prolonged elevations of microdialysate NE, as well as plasma ACTH and corticosterone, and body temperature. IL-1beta also induced shivering and a prolonged depression of locomotor activity. Pretreatment with indomethacin (10 mg/kg sc) prevented the IL-1beta-induced increases in body temperature and the apparent increase in hypothalamic NE release, but only attenuated the IL-1beta-induced shivering and the increase in plasma ACTH. The results indicate a close temporal relationship between the release of NE and HPA axis activation. Such a relationship is also supported by the similar effects of indomethacin pretreatment on NE and ACTH. The shivering is likely involved in the increase in body temperature, but indomethacin only attenuated the shivering while it blocked the fever. However, the effects of indomethacin clearly indicate that neither the increase in body temperature nor the increase in hypothalamic NE release was essential for HPA axis activation. These results suggest that hypothalamic NE is involved in the IL-1-induced HPA axis activation, but that this is not the only mechanism by which the HPA axis is activated by intraperitoneally injected IL-1.

An autophagic mechanism is involved in the 6-hydroxydopamine-induced neurotoxicity in vivo.

PubMed

He, Xin; Yuan, Wei; Li, Zijian; Feng, Juan

2017-10-05

6-hydroxydopamine (6-OHDA) is one of the most common agents for modeling dopaminergic neuron degeneration in Parkinson's disease (PD). So far, the role of autophagy in 6-OHDA-induced neurotoxicity remains controversial and most evidence is collected from in vitro studies. In this study, we determined the role of autophagy activation in 6-OHDA-induced neurotoxicity in a rat model of PD. Following 6-OHDA treatment, we observed a concomitant activation of autophagy and apoptosis. To further explore the interaction between autophagy and apoptosis induced by 6-OHDA, autophagy inhibitor 3-methylademine (3-MA) or cysteine protease inhibitor Z-FA-fmk was applied. We found that both 3-MA and Z-FA-fmk could not only exert immediate protection against 6-OHDA-induced neuronal apoptosis, but also prevent dopaminergic neuron loss in the long-term, which was related to reduced autophagosome formation. Furthermore, by monitoring the sequential changes of mTOR-related signaling pathways, we found that reactive oxygen species (ROS)-mediated AKT/AMPK-mTOR signaling pathway participated in but was not the initial cause of autophagy activation by 6-OHDA. Collectively, our data suggest that 6-OHDA-induced autophagy activation contributes to its neurotoxicity and targeting autophagy activation or cysteine proteases could be promising for developing neuroprotective agents for PD. Copyright © 2017 Elsevier B.V. All rights reserved.

Monitoring Cyp2b10 mRNA expression at cessation of 2-year carcinogenesis bioassay in mouse liver provides evidence for a carcinogenic mechanism devoid of human relevance: The dalcetrapib experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoflack, J-C.; Mueller, L., E-mail: Lutz.Mueller@roche.com; Fowler, S.

2012-03-15

Introduction: Dalcetrapib is a cholesteryl ester transfer protein (CETP) modulator in clinical assessment for cardiovascular outcome benefits. In compliance with regulatory requirements, dalcetrapib was evaluated in rodent 2-year carcinogenesis bioassays. In the mouse bioassay, male mice demonstrated increased liver weight and statistically increased incidences of hepatocellular adenoma/carcinoma. Hepatic cytochrome p450 (Cyp) 2b10 mRNA induction and increased Cyp2b10 enzyme activity signify activation of hepatic nuclear receptor constitutive androstane receptor (CAR), a widely established promoter of rodent-specific hepatic tumors. We therefore monitored hepatic Cyp2b10 mRNA and its enzyme activity in a subset of dalcetrapib-treated male mice from the bioassay. Methods: Liver samplesmore » were obtained from ∼ 1/3 of male mice from each dose group including vehicle-controls (mean and earliest study day of death 678 and 459 respectively). Quantitative real time PCR (qRT-PCR) was performed to determine Cyp2b10 mRNA expression and Cyp1a-, Cyp2b10- and Cyp3a-selective activities were monitored. Results: Cyp2b10 mRNA was strongly induced by dalcetrapib with an expected wide inter-individual variation (5–1421-fold). Group average fold-induction versus vehicle-controls showed a dose-related increase from 48-fold (250 mg/kg/day) to 160-fold (750 mg/kg/day), which declined slightly at 2000 mg/kg/day (97-fold). Cyp enzyme activities showed approximate doubling of total Cyp P450 content per milligram protein and a 9-fold increase in Cyp2b10-selective pentoxyresorufin O-dealkylase activity (750 mg/kg/day). Discussion: These data from hepatic Cyp2b10 monitoring are strongly suggestive of CAR activation by dalcetrapib, a mechanism devoid of relevance towards hepatocarcinogenesis in humans; results show feasibility of Cyp2b10 as a surrogate marker for this mechanism at cessation of a carcinogenesis bioassay. -- Highlights: ► Liver tumors were induced in male mice by dalcetrapib in a 2-y study (bioassay). ► Cyp2b10 induction typifies activation of nuclear receptor CAR in mouse liver. ► First report of hepatic Cyp2b10 monitoring at the end of a mouse bioassay. ► Cyp2b10 induction supports CAR activation by dalcetrapib in mouse bioassay. ► CAR activation is a mechanism of hepatic tumorigenesis of no relevance to humans.« less

Technical support for geopressured-geothermal well activities in Louisiana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-07-01

Continuous recording microearthquake monitoring networks have been established around US Department of Energy (DOE) geopressured-geothermal design wells in southwestern Louisiana and southeastern Texas since summer 1980 to assess the effects well development may have had on subsidence and growth-fault activation. This monitoring has shown several unusual characteristics of Gulf Coast seismic activity. The observed activity is classified into two dominant types, one with identifiable body phases (type 1) and the other with only surface-wave signatures (type 2). During this reporting period no type 1 or body-wave events were reported. A total of 230 type 2 or surface-wave events were recorded.more » Origins of the type 2 events are still not positively understood; however, little or no evidence is available to connect them with geopressured-geothermal well activity. We continue to suspect sonic booms from military aircraft or some other human-induced source. 37 refs., 16 figs., 6 tabs.« less

Application of the FRET method for monitoring the dynamics of caspase-3 activation during apoptosis in living cells

NASA Astrophysics Data System (ADS)

Chen, Tongsheng; Xing, Da

2005-01-01

Activation of caspase-3 is a central event in apoptosis. A fluorescence techniques, fluorescence resonance energy transfer (FRET), was used to study the dynamic of caspase-3 activation during apoptosis induced by tumor necrosis factor TNF-α in living cells. The FRET probe consists a CFP (cyan fluorescent protein) and a Venus (YFP mutant, yellow fluorescent protein) with a specialized linker containing the caspase-3 cleavage sequence: DEVD (Luo et al., 2001). Human lung adenocarcinoma cell line (ASTC-a-1) were stably expressed with the FRET probe and then were treated by TNF-α, respectively. Experimental results showed that FRET could monitor more insensitively the dynamic of caspase-3 activation in real-time in vivo, and this technique will be highly useful for correlating the caspase-3 activation with other apoptotic events and for rapid-screening of potential drugs that may target the apoptotic process.

A new device for monitoring early motor development: prenatal nicotine-induced changes.

PubMed

Schlumpf, M; Gähwiler, M; Ribary, U; Lichtensteiger, W

1988-05-01

A new type of activity meter has been designed especially for young rats. It consists of a warmed platform for the animal, a TV camera with monitor and a microprocessor. The TV camera detects the animal as a black figure on a light background. This picture is digitalized and stored in a Z80 microprocessor. Every 200 msec a new image is compared to the foregoing one. The total number of black points that are changing from black to white and vice versa provides a measure for motor activity of the animal. Prenatally nicotine-treated rat pups were tested on the activity meter. The developmental pattern of motor activity was different for male and female pups. Motor activity of nicotine-treated male pups differed significantly from controls at postnatal days 7 and 15 while this drug effect was not seen in females.

Pummelo Protects Doxorubicin-Induced Cardiac Cell Death by Reducing Oxidative Stress, Modifying Glutathione Transferase Expression, and Preventing Cellular Senescence

PubMed Central

Chularojmontri, L.; Gerdprasert, O.; Wattanapitayakul, S. K.

2013-01-01

Citrus flavonoids have been shown to reduce cardiovascular disease (CVD) risks prominently due to their antioxidant effects. Here we investigated the protective effect of pummelo (Citrus maxima, CM) fruit juice in rat cardiac H9c2 cells against doxorubicin (DOX-) induced cytotoxicity. Four antioxidant compositions (ascorbic acid, hesperidin, naringin, and gallic acid) were determined by HPLC. CM significantly increased cardiac cell survival from DOX toxicity as evaluated by MTT assay. Reduction of cellular oxidative stress was monitored by the formation of DCF fluorescent product and total glutathione (GSH) levels. The changes in glutathione-S-transferase (GST) activity and expression were determined by enzyme activity assay and Western blot analysis, respectively. Influence of CM on senescence-associated β-galactosidase activity (SA-β-gal) was also determined. The mechanisms of cytoprotection involved reduction of intracellular oxidative stress, maintaining GSH availability, and enhanced GST enzyme activity and expression. DOX-induced cellular senescence was also attenuated by long-term CM treatment. Thus, CM fruit juice can be promoted as functional fruit to protect cells from oxidative cell death, enhance the phase II GSTP enzyme activity, and decrease senescence phenotype population induced by cardiotoxic agent such as DOX. PMID:23401708

Chemical Strategy to Translate Genetic/epigenetic Mechanisms to Breast Cancer Therapeutics

DTIC Science & Technology

2012-07-01

androgen-sensitive LNCaP cells. Early studies suggest that cardiac glycosides inhibit cell pro- liferation through the induction of apoptosis (24–26...We asked whether induced apoptosis was sufficient to account for the strong effect of Peruvoside on inhibiting cell proliferation. By monitoring...activated Caspases 3 and 7, we found that Peruvoside has a de- tectable degree of induced apoptosis on LNCaP cells, but no effect on LNCaP-abl cells (Fig

Detecting the climatic effects of increasing carbon dioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacCracken, M C; Luther, F M

1985-12-01

This report documents what is known about detecting the CO2-induced changes in climate, and describes the uncertainties and unknowns associated with this monitoring and analysis effort. The various approaches for detecting CO2-induced climate changes are discussed first, followed by a review of applications of these strategies to the various climatic variables that are expected to be changing. Recommendations are presented for research and analysis activities. Separate abstracts have been prepared for the individual papers. (ACR)

AMP-activated protein kinase (AMPK)-induced preconditioning in primary cortical neurons involves activation of MCL-1.

PubMed

Anilkumar, Ujval; Weisová, Petronela; Düssmann, Heiko; Concannon, Caoimhín G; König, Hans-Georg; Prehn, Jochen H M

2013-03-01

Neuronal preconditioning is a phenomenon where a previous exposure to a sub-lethal stress stimulus increases the resistance of neurons towards a second, normally lethal stress stimulus. Activation of the energy stress sensor, AMP-activated protein kinase (AMPK) has been shown to contribute to the protective effects of ischaemic and mitochondrial uncoupling-induced preconditioning in neurons, however, the molecular basis of AMPK-mediated preconditioning has been less well characterized. We investigated the effect of AMPK preconditioning using 5-aminoimidazole-4-carboxamide riboside (AICAR) in a model of NMDA-mediated excitotoxic injury in primary mouse cortical neurons. Activation of AMPK with low concentrations of AICAR (0.1 mM for 2 h) induced a transient increase in AMPK phosphorylation, protecting neurons against NMDA-induced excitotoxicity. Analysing potential targets of AMPK activation, demonstrated a marked increase in mRNA expression and protein levels of the anti-apoptotic BCL-2 family protein myeloid cell leukaemia sequence 1 (MCL-1) in AICAR-preconditioned neurons. Interestingly, over-expression of MCL-1 protected neurons against NMDA-induced excitotoxicity while MCL-1 gene silencing abolished the effect of AICAR preconditioning. Monitored intracellular Ca²⁺ levels during NMDA excitation revealed that MCL-1 over-expressing neurons exhibited improved bioenergetics and markedly reduced Ca²⁺ elevations, suggesting a potential mechanism through which MCL-1 confers neuroprotection. This study identifies MCL-1 as a key effector of AMPK-induced preconditioning in neurons. © 2012 International Society for Neurochemistry.

Involvement of Bim in Photofrin-mediated photodynamically induced apoptosis.

PubMed

Wang, Xianwang; He, Xiaobing; Hu, Shujuan; Sun, Anbang; Lu, Chengbiao

2015-01-01

Photodynamic therapy (PDT) is a promising noninvasive technique, which has been successfully applied to the treatment of human cancers. Studies have shown that the Bcl-2 family proteins play important roles in PDT-induced apoptosis. However, whether Bcl-2-interacting mediator of cell death (Bim) is involved in photodynamic treatment remains unknown. In this study, we attempt to determine the effect of Bim on Photofrin photodynamic treatment (PPT)-induced apoptosis in human lung adenocarcinoma ASTC-a-1 cells. The translocation of Bim/Bax of the cells were monitored by laser confocal scanning microscope. The levels of Bim protein and activated caspase-3 in cells were detected by western blot assay. Caspase-3 activities were measured by Caspase-3 Fluorogenic Substrate (Ac-DEVD-AFC) analysis. The induction of apoptosis was detected by Hoechst 33258 and PI staining as well as flow cytometry analysis. The effect of Bim on PPT-induced apoptosis was determined by RNAi. BimL translocated to mitochondria in response to PPT, similar to the downstream pro-apoptotic protein Bax activation. PPT increased the level of Bim and activated caspase-3 in cells and that knockdown of Bim by RNAi significantly protected against caspase-3 activity. PPT-induced apoptosis were suppressed in cells transfected with shRNA-Bim. We demonstrated the involvement of Bim in PPT-induced apoptosis in human ASTC-a-1 lung adenocarcinoma cells and suggested that enhancing Bim activity might be a potential strategy for treating human cancers. © 2015 S. Karger AG, Basel.

Space Station Induced Monitoring

NASA Technical Reports Server (NTRS)

Spann, James F. (Editor); Torr, Marsha R. (Editor)

1988-01-01

This report contains the results of a conference convened May 10-11, 1988, to review plans for monitoring the Space Station induced environment, to recommend primary components of an induced environment monitoring package, and to make recommendations pertaining to suggested modifications of the Space Station External Contamination Control Requirements Document JSC 30426. The contents of this report are divided as Follows: Monitoring Induced Environment - Space Station Work Packages Requirements, Neutral Environment, Photon Emission Environment, Particulate Environment, Surface Deposition/Contamination; and Contamination Control Requirements.

Multisensor of Remotely Sensed Data for Characterizing Seismotectonic Activities in Malaysia

NASA Astrophysics Data System (ADS)

Abu Bakar, Rabieahtul; Azahari Razak, Khamarrul; Anuar Jamaludin, Tajul; Tongkul, Felix; Mohamad, Zakaria; Ramli, Zamri; Abd Manap, Mohamad; Rahman, Muhammad Zulkarnain Abdul

2015-04-01

Seismically induced events pose serious hazards yet are difficult to predict. Despite remarkable efforts of mapping, monitoring and modelling of such great events at regional or local scales, the understanding of the processes in the Earth's dynamic system remains elusive. Although Malaysia is in a relatively low seismic hazard zone, the current trend and pattern of seismotectonic activities triggered a series of fundamental study to better understand the relationship between the earthquakes, recent tectonics and seismically active fault zones. Several conventional mapping techniques have been intensively used but shown some limitations. Remote sensing is the preferable mean to quantify the seismic activity accurately in a larger area within a short period. Still, only few of such studies have been carried out in this subduction region. Characterization of seismotectonic activities from space in a tropical environment is very challenging given the complexity of its physiographic, climatic, geologic conditions and anthropogenic activities. There are many factors controlling the success rate of the implementation mainly due to the lack of historical earthquakes, geomorphological evidence, and proper identification of regional tectonic patterns. In this study, we aim at providing better insight to extract and characterize seismotectonic activities by integrating passive and active remotely-sensed data, geodetic data, historical records, GIS-based data analysis and in-situ measurements as well quantify them based on field investigation and expert knowledge. It is crucial to perform spatiotemporal analysis of its activities in the most seismically induced region in North-Western Sabah. A comprehensive geodatabase of seismotectonic events are developed and allowed us to analyse the spatiotemporal activities. A novelty of object-based image method for extracting tropical seismically active faults and related seismotectonic features are introduced and evaluated. We aim to develop the exchangeable and transferable rule-set with optimal parameterization for such aforementioned tasks. A geomorphometric-based remotely sensed approach is used to understand the tectonic geomorphology in processes affecting the environment at different spatial scales. As a result of this study, questions related to cascading natural disasters, e.g. landslides can be quantitatively answered. Development and applications of seismically induced landslide hazard and risk zonation at different scales are conceptually presented and critically discussed. So far, quantification evaluation of uncertainties associated to spatial seismic hazard and risks prediction remains very challenging to understand and it is an interest of on-going research. In the near-future, it is crucial to address the changes of climate and land-use-land-cover in relation to temporal and spatial pattern of seismically induced landslides. It is also important to assess, model and incorporate the changes due to natural disasters into a sustainable risk management. As a conclusion, the characteristics, development and function of tectonic movement, as one of the components for geomorphological process-response system is crucial for a regional seismic study. With newly emerging multi-sensor of remotely sensed data coupled with the satellite positioning system promises a better mapping and monitoring tool for seismotectonic activities in such a way that it can be used to map, monitor, and model related seismically induced processes for a comprehensive hazard and associated risk assessment.

Clopidogrel (Plavix) and cardiac surgical patients: implications for platelet function monitoring and postoperative bleeding.

PubMed

Tanaka, Kenichi A; Szlam, Fania; Kelly, Andrew B; Vega, J David; Levy, Jerrold H

2004-08-01

The use of clopidogrel (Plavix), an inhibitor of adenosine diphosphate (ADP)-induced platelet aggregation, has been proven to reduce ischemic events in cardiovascular patients, but little information is available for optimal monitoring of platelet function in patients receiving the drug preoperatively. In the first part of the study we compared different testing modalities (thrombelastography (TEG), platelet aggregometry, and whole blood aggregation) to assess platelet ADP receptor inhibition. Because clopidogrel is a pro-drug, we used an in vitro model of ADP inhibition with 5'-p-fluorosulfonylbenzoyladenosine (FSBA). FSBA at final concentration of 80 microM completely inhibited platelet aggregation but had no effect on TEG maximum amplitude (MA). In the second part of the study, antiplatelet effects of clopidogrel were clinically assessed and correlated to postoperative bleeding in 18 coronary bypass surgery patients. Preoperative TEG results were normal or hypercoagulable in clopidogrel-treated patients, although platelet aggregation responses to ADP were inhibited. Clopidogrel-treated patients who underwent cardiopulmonary bypass had a high incidence (84.6%) of platelet transfusion therapy due to increased chest tube drainage. In conclusion, we have demonstrated that normal preoperative TEG-MA does not preclude clopidogrel-induced ADP receptor blockade; however, TEG can be a reliable monitor for CPB-induced platelet dysfunction related to GPIIb/IIIa. For monitoring clopidogrel, it is necessary to perform more specific platelet function tests (aggregometry or platelet count ratio) using ADP as an activator.

Photoacoustic imaging to detect rat brain activation after cocaine hydrochloride injection

NASA Astrophysics Data System (ADS)

Jo, Janggun; Yang, Xinmai

2011-03-01

Photoacoustic imaging (PAI) was employed to detect small animal brain activation after the administration of cocaine hydrochloride. Sprague Dawley rats were injected with different concentrations (2.5, 3.0, and 5.0 mg per kg body) of cocaine hydrochloride in saline solution through tail veins. The brain functional response to the injection was monitored by photoacoustic tomography (PAT) system with horizontal scanning of cerebral cortex of rat brain. Photoacoustic microscopy (PAM) was also used for coronal view images. The modified PAT system used multiple ultrasonic detectors to reduce the scanning time and maintain a good signal-to-noise ratio (SNR). The measured photoacoustic signal changes confirmed that cocaine hydrochloride injection excited high blood volume in brain. This result shows PAI can be used to monitor drug abuse-induced brain activation.

Magnetic Graphene Nanosheet-Based Microfluidic Device for Homogeneous Real-Time Electronic Monitoring of Pyrophosphatase Activity Using Enzymatic Hydrolysate-Induced Release of Copper Ion.

PubMed

Lin, Youxiu; Zhou, Qian; Li, Juan; Shu, Jian; Qiu, Zhenli; Lin, Yuping; Tang, Dianping

2016-01-05

A novel flow-through microfluidic device based on a magneto-controlled graphene sensing platform was designed for homogeneous electronic monitoring of pyrophosphatase (PPase) activity; enzymatic hydrolysate-induced release of inorganic copper ion (Cu(2+)) from the Cu(2+)-coordinated pyrophosphate ions (Cu(2+)-PPi) complex was assessed to determine enzyme activity. Magnetic graphene nanosheets (MGNS) functionalized with negatively charged Nafion were synthesized by using the wet-chemistry method. The Cu(2+)-PPi complexes were prepared on the basis of the coordination reaction between copper ion and inorganic pyrophosphate ions. Upon target PPase introduction into the detection system, the analyte initially hydrolyzed pyrophosphate ions into phosphate ions and released the electroactive copper ions from Cu(2+)-PPi complexes. The released copper ions could be readily captured through the negatively charged Nafion on the magnetic graphene nanosheets, which could be quantitatively monitored by using the stripping voltammetry on the flow-through detection cell with an external magnet. Under optimal conditions, the obtained electrochemical signal exhibited a high dependence on PPase activity within a dynamic range from 0.1 to 20 mU mL(-1) and allowed the detection at a concentration as low as 0.05 mU mL(-1). Coefficients of variation for reproducibility of the intra-assay and interassay were below 7.6 and 9.8%, respectively. The inhibition efficiency of sodium fluoride (NaF) also received good results in pyrophosphatase inhibitor screening research. In addition, the methodology afforded good specificity and selectivity, simplification, and low cost without the need of sample separations and multiple washing steps, thus representing a user-friendly protocol for practical utilization in a quantitative PPase activity.

Cardiopulmonary bypass with bivalirudin in type II heparin-induced thrombocytopenia.

PubMed

Clayton, Stephanie B; Acsell, Jeffrey R; Crumbley, Arthur J; Uber, Walter E

2004-12-01

Cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia poses significant challenges. Inadequate pharmacokinetic profiles, monitoring, reversibility, and availability often limit alternative anticoagulation strategies. Bivalirudin, a semisynthetic direct thrombin inhibitor, was recently approved for use in patients undergoing percutaneous coronary interventions. Its unique properties, including a relatively short half-life, an anticoagulation effect that closely correlates with activated clotting time, and an alternate metabolic pathway for elimination, make bivalirudin an attractive agent for cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia. We report our experience using bivalirudin in 2 patients undergoing coronary artery bypass grafting.

Retrospective application of the "guidelines for monitoring mining subsurface activities for hydrocarbons exploitation, re-injection and storage activities (ILG)": insights from the analysis of 2012-2013 Emilia seismic sequence at the Cavone oilfield pilot site (Italy)

NASA Astrophysics Data System (ADS)

Buttinelli, M.; Chiarabba, C.; Anselmi, M.; Pezzo, G.; Improta, L.; Antoncecchi, I.

2017-12-01

In recent years, the debate on the interactions between wastewater disposal and induced seismicity is increasingly drawing the attention of the scientific community, since injections by high-rate wells have been directly associated to occurrence of even large seismic events. In February 2014, the Italian Ministry of Economic Development (MiSE), within the Commission on Hydrocarbon and Mining Resources (CIRM), issued the "guidelines for monitoring mining subsurface activities for hydrocarbons exploitation, re-injection and storage activities (ILG)". The ILG represent the first action in italy aimed at keeping the safety standards mostly in areas where the underground resources exploitation can induce seismicity, ground deformations and pore pressure changes of the reservoirs. Such guidelines also launched a "traffic light" operating system, for the first time defining threshold values and activation levels for such monitored parameters. To test the ILG implications (in particular of the traffic light system) we select the Cavone oilfield (Northern Italy) as test case, since this area was interested during the 2012-2013 by the Emilia Seismic sequence. Moreover, the potential influence of the Cavone oilfield activities in the 2012 earthquake trigger was debated for a long time within the scientific and not contexts, highlighting the importance of seismic monitoring in hydrocarbons exploitation, re-injection and storage areas. In this work we apply the ILG retrospectively to the Cavone oilfield and surrounding areas, just for the seismicity parameter (pore pressure and ground deformation were not taken into account because out of the traffic light system). Since each seismicity catalogue available for the 2012 sequence represents a different setting of monitoring system, we carefully analyzed how the use of such catalogues impact on the overcoming of the threshold imposed by the ILG. In particular, we focus on the use of 1D and 3D velocity models developed ad hoc or not for the investigated area. Results show that different approaches strongly affect the location of seismic event, therefore generating proper or un-proper warnings applying the traffic light system. Our analysis also highlighted the importance of accounting for local geological complexity in the seismicity location strategy.

Activation of proteolytic enzymes and depression of the sarcolemmal Na+/K+-ATPase in ischemia-reperfused heart may be mediated through oxidative stress.

PubMed

Singh, Raja B; Hryshko, Larry; Freed, Darren; Dhalla, Naranjan S

2012-02-01

We tested whether the activation of proteolytic enzymes, calpain, and matrix metalloproteinases (MMPs) during ischemia-reperfusion (I/R) is mediated through oxidative stress. For this purpose, isolated rat hearts were subjected to a 30 min global ischemia followed by a 30 min reperfusion. Cardiac function was monitored and the activities of Na(+)/K(+)-ATPase, Mg(2+)-ATPase, calpain, and MMP were measured. Depression of cardiac function and Na(+)/K(+)-ATPase activity in I/R hearts was associated with increased calpain and MMP activities. These alterations owing to I/R were similar to those observed in hearts perfused with hypoxic medium, H(2)O(2) and xanthine plus xanthine oxidase. The I/R-induced changes were attenuated by ischemic preconditioning as well as by perfusing the hearts with N-acetylcysteine or mercaptopropionylglycine. Inhibition of MMP activity in hearts treated with doxycycline depressed the I/R-induced changes in cardiac function and Na(+)/K(+)-ATPase activity without affecting the calpain activation. On the other hand, inhibition of calpain activity upon treatment with leupeptin or MDL 28170 significantly reduced the MMP activity in addition to attenuating the I/R-induced alterations in cardiac function and Na(+)/K(+)-ATPase activity. These results suggest that the I/R-induced depression in Na(+)/K(+)-ATPase and cardiac function may be a consequence of the increased activities of both calpain and MMP because of oxidative stress in the heart.

A portable magnetic induction measurement system (PIMS).

PubMed

Cordes, Axel; Foussier, Jérôme; Pollig, Daniel; Leonhardt, Steffen

2012-02-22

For contactless monitoring of ventilation and heart activity, magnetic induction measurements are applicable. As the technique is harmless for the human body, it is well suited for long-term monitoring solutions, e.g., bedside monitoring, monitoring of home care patients, and the monitoring of persons in critical occupations. For such settings, a two-channel portable magnetic induction system has been developed, which is small and light enough to be fitted in a chair or bed. Because demodulation, control, and filtering are implemented on a front-end digital signal processor, a PC is not required (except for visualization/data storage during research and development). The system can be connected to a local area network (LAN) or wireless network (WiFi), allowing to connect several devices to a large monitoring system, e.g., for a residential home for the elderly or a hospital with low-risk patients not requiring standard ECG monitoring. To visualize data streams, a Qt-based (Qt-framework by Nokia, Espoo, Finland) monitoring application has been developed, which runs on Netbook computers, laptops, or standard PCs. To induce and measure the magnetic fields, external coils and amplifiers are required. This article describes the system and presents results for monitoring respiration and heart activity in a (divan) bed and for respiration monitoring in a chair. Planar configurations and orthogonal coil setups were examined during the measurement procedures. The measurement data were streamed over a LAN to a monitoring PC running Matlab (The MathWorks Inc, Natick, MA, USA).

Changes in hormone and stress-inducing activities of municipal wastewater in a conventional activated sludge wastewater treatment plant.

PubMed

Wojnarowicz, Pola; Yang, Wenbo; Zhou, Hongde; Parker, Wayne J; Helbing, Caren C

2014-12-01

Conventional municipal wastewater treatment plants do not efficiently remove contaminants of emerging concern, and so are primary sources for contaminant release into the aquatic environment. Although these contaminants are present in effluents at ng-μg/L concentrations (i.e. microcontaminants), many compounds can act as endocrine disrupting compounds or stress-inducing agents at these levels. Chemical fate analyses indicate that additional levels of wastewater treatment reduce but do not always completely remove all microcontaminants. The removal of microcontaminants from wastewater does not necessarily correspond to a reduction in biological activity, as contaminant metabolites or byproducts may still be biologically active. To evaluate the efficacy of conventional municipal wastewater treatment plants to remove biological activity, we examined the performance of a full scale conventional activated sludge municipal wastewater treatment plant located in Guelph, Ontario, Canada. We assessed reductions in levels of conventional wastewater parameters and thyroid hormone disrupting and stress-inducing activities in wastewater at three phases along the treatment train using a C-fin assay. Wastewater treatment was effective at reducing total suspended solids, chemical and biochemical oxygen demand, and stress-inducing bioactivity. However, only minimal reduction was observed in thyroid hormone disrupting activities. The present study underscores the importance of examining multiple chemical and biological endpoints in evaluating and monitoring the effectiveness of wastewater treatment for removal of microcontaminants. Copyright © 2014 Elsevier Ltd. All rights reserved.

In-line monitoring of Li-ion battery electrode porosity and areal loading using active thermal scanning - modeling and initial experiment

DOE PAGES

Rupnowski, Przemyslaw; Ulsh, Michael J.; Sopori, Bhushan; ...

2017-08-18

This work focuses on a new technique called active thermal scanning for in-line monitoring of porosity and areal loading of Li-ion battery electrodes. In this technique a moving battery electrode is subjected to thermal excitation and the induced temperature rise is monitored using an infra-red camera. Static and dynamic experiments with speeds up to 1.5 m min -1 are performed on both cathodes and anodes and a combined micro- and macro-scale finite element thermal model of the system is developed. It is shown experimentally and through simulations that during thermal scanning the temperature profile generated in an electrode depends onmore » both coating porosity (or area loading) and thickness. Here, it is concluded that by inverting this relation the porosity (or areal loading) can be determined, if thermal response and thickness are simultaneously measured.« less

In-line monitoring of Li-ion battery electrode porosity and areal loading using active thermal scanning - modeling and initial experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rupnowski, Przemyslaw; Ulsh, Michael J.; Sopori, Bhushan

This work focuses on a new technique called active thermal scanning for in-line monitoring of porosity and areal loading of Li-ion battery electrodes. In this technique a moving battery electrode is subjected to thermal excitation and the induced temperature rise is monitored using an infra-red camera. Static and dynamic experiments with speeds up to 1.5 m min -1 are performed on both cathodes and anodes and a combined micro- and macro-scale finite element thermal model of the system is developed. It is shown experimentally and through simulations that during thermal scanning the temperature profile generated in an electrode depends onmore » both coating porosity (or area loading) and thickness. Here, it is concluded that by inverting this relation the porosity (or areal loading) can be determined, if thermal response and thickness are simultaneously measured.« less

In-line monitoring of Li-ion battery electrode porosity and areal loading using active thermal scanning - modeling and initial experiment

NASA Astrophysics Data System (ADS)

Rupnowski, Przemyslaw; Ulsh, Michael; Sopori, Bhushan; Green, Brian G.; Wood, David L.; Li, Jianlin; Sheng, Yangping

2018-01-01

This work focuses on a new technique called active thermal scanning for in-line monitoring of porosity and areal loading of Li-ion battery electrodes. In this technique a moving battery electrode is subjected to thermal excitation and the induced temperature rise is monitored using an infra-red camera. Static and dynamic experiments with speeds up to 1.5 m min-1 are performed on both cathodes and anodes and a combined micro- and macro-scale finite element thermal model of the system is developed. It is shown experimentally and through simulations that during thermal scanning the temperature profile generated in an electrode depends on both coating porosity (or area loading) and thickness. It is concluded that by inverting this relation the porosity (or areal loading) can be determined, if thermal response and thickness are simultaneously measured.

Establishment of a sensor testbed at NIST for plant productivity monitoring

NASA Astrophysics Data System (ADS)

Allen, D. W.; Hutyra, L.; Reinmann, A.; Trlica, A.; Marrs, J.; Jones, T.; Whetstone, J. R.; Logan, B.; Reblin, J.

2017-12-01

Accurate assessments of biogenic carbon fluxes is challenging. Correlating optical signatures to plant activity allows for monitoring large regions. New methods, including solar-induced fluorescence (SIF), promise to provide more timely and accurate estimate of plant activity, but we are still developing a full understanding of the mechanistic leakage between plant assimilation of carbon and SIF. We have initiated a testbed to facilitate the evaluation of sensors and methods for remote monitoring of plant activity at the NIST headquarters. The test bed utilizes a forested area of mature trees in a mixed urban environment. A 1 hectare plot within the 26 hectare forest has been instrumented for ecophysiological measurements with an edge (100 m long) that is persistently monitored with multimodal optical sensors (SIF spectrometers, hyperspectral imagers, thermal infrared imaging, and lidar). This biological testbed has the advantage of direct access to the national scales maintained by NIST of measurements related to both the physical and optical measurements of interest. We offer a description of the test site, the sensors, and preliminary results from the first season of observations for ecological, physiological, and remote sensing based estimates of ecosystem productivity.

On the watch for geomagnetic storms

USGS Publications Warehouse

Green, Arthur W.; Brown, William M.

1997-01-01

Geomagnetic storms, induced by solar activity, pose significant hazards to satellites, electrical power distribution systems, radio communications, navigation, and geophysical surveys. Strong storms can expose astronauts and crews of high-flying aircraft to dangerous levels of radiation. Economic losses from recent geomagnetic storms have run into hundreds of millions of dollars. With the U.S. Geological Survey (USGS) as the lead agency, an international network of geomagnetic observatories monitors the onset of solar-induced storms and gives warnings that help diminish losses to military and commercial operations and facilities.

Effect of Allium flavum L. and Allium melanantherum Panč. Extracts on Oxidative DNA Damage and Antioxidative Enzymes Superoxide Dismutase and Catalase.

PubMed

Mitić-Ćulafić, Dragana; Nikolić, Biljana; Simin, Nataša; Jasnić, Nebojša; Četojević-Simin, Dragana; Krstić, Maja; Knežević-Vukčević, Jelena

2016-03-01

Allium flavum L. and Allium melanantherum Panč. are wild growing plants used in traditional diet in Balkan region. While chemical composition and some biological activities of A. flavum have been reported, A. melanantherum, as an endemic in the Balkan Peninsula, has never been comprehensively examined. After chemical characterization of A. melanantherum, we examined the protective effect of methanol extracts of both species against t-butyl hydro-peroxide (t-BOOH)-induced DNA damage and mutagenesis. The bacterial reverse mutation assay was performed on Escherichia coli WP2 oxyR strain. DNA damage was monitored in human fetal lung fibroblasts (MRC-5) with alkaline comet assay. Obtained results indicated that extracts reduced t-BOOH-induced DNA damage up to 70 and 72% for A. flavum and A. melanantherum extract, respectively, and showed no effect on t-BOOH-induced mutagenesis. Since the results indicated modulatory effect on cell-mediated antioxidative defense, the effect of extracts on total protein content, and superoxide dismutase (SOD) and catalase (CAT) amounts and activities were monitored. Both extracts increased total protein content, while the increase of enzyme amount and activity was obtained only with A. melanantherum extract and restricted to CAT. The activity of CuZnSOD family was not affected, while SOD1 and SOD2 amounts were significantly decreased, indicating potential involvement of extracellular CuZnSOD. Obtained results strongly support the traditional use of A. flavum and A. melanantherum in nutrition and recommend them for further study.

Heptachlor induced nigral dopaminergic neuronal loss and Parkinsonism-like movement deficits in mice

PubMed Central

Hong, Seokheon; Hwang, Joohyun; Kim, Joo Yeon; Shin, Ki Soon; Kang, Shin Jung

2014-01-01

Epidemiological studies have suggested an association between pesticide exposure and Parkinson's disease. In this study, we examined the neurotoxicity of an organochlorine pesticide, heptachlor, in vitro and in vivo. In cultured SH-SY5Y cells, heptachlor induced mitochondria-mediated apoptosis. When injected into mice intraperitoneally on a subchronic schedule, heptachlor induced selective loss of dopaminergic neurons in the substantia nigra pars compacta. In addition, the heptachlor injection induced gliosis of microglia and astrocytes selectively in the ventral midbrain area. When the general locomotor activities were monitored by open field test, the heptachlor injection did not induce any gross motor dysfunction. However, the compound induced Parkinsonism-like movement deficits when assessed by a gait and a pole test. These results suggest that heptachlor can induce Parkinson's disease-related neurotoxicities in vivo. PMID:24577234

WE-E-BRE-12: Tumor Microenvironment Dynamics Following Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campos, D; Niles, D; Adamson, E

2014-06-15

Purpose: This work aims to understand the radiation-induced interplay between tumor oxygenation and metabolic activity. These dynamics can potentially serve as biomarkers in assessing treatment response allowing for patient-specific adaptive radiotherapy. Methods: Using patient-derived xenografts of head and neck cancer we assessed tumor oxygenation via fiber-optic probe monitored hemoglobin saturation and Blood Oxygen Level Dependent (BOLD) MRI. Measurements were taken before and after a 10 Gy dose of radiation. Changes in metabolic activity were measured via Fluorescence Lifetime IMaging (FLIM) with the appropriate controls following a 10 Gy dose of radiation. FLIM can non-invasively monitor changes in fluorescence in responsemore » to the microenvironment including being able to detect free and bound states of the intrinsically fluorescent metabolite NADH (Nicotinamide Adenine Dinucleotide). With this information FLIM can accurately quantify the metabolic state of cells that have been radiated. To model the observed changes, a two-compartment, source-sink simulation relating hemoglobin saturation and metabolic activity was performed using MATLAB. Results: Hemoglobin saturation as measured by interstitial probe and BOLD-MRI decreased by 30% within 15 minutes following radiation. FLIM demonstrated a decrease in the mean fluorescence lifetime of NADH by 100 ps following 10 Gy indicating a shift towards glycolytic pathways. Simulation of radiation-induced alterations in tumor oxygenation demonstrated that these changes can be the result of changes in either vasculature or metabolic activity. Conclusion: Radiation induces significant changes in hemoglobin saturation and metabolic activity. These alterations occur on time scales approximately the duration of common radiation treatments. Further understanding these dynamics has important implications with regard to improvement of therapy and biomarkers of treatment response.« less

Combining microseismic and geomechanical observations to interpret storage integrity at the In Salah CCS site

NASA Astrophysics Data System (ADS)

Goertz-Allmann, Bettina P.; Kühn, Daniela; Oye, Volker; Bohloli, Bahman; Aker, Eyvind

2014-07-01

We present results from microseismic monitoring and geomechanical analysis obtained at the industrial-scale CO2 sequestration site at the In Salah gas development project in Algeria. More than 5000 microseismic events have been detected at a pilot monitoring well using a master event cross-correlation method. The microseismic activity occurs in four distinct clusters and thereof three clearly correlate with injection rates and wellhead pressures. These event clusters are consistent with a location within the reservoir interval. However, due to insufficient network geometry there are large uncertainties on event location. We estimate a fracture pressure of 155 bar (at the wellhead) from the comparison of injection pressure and injection rate and conclude that reservoir fracture pressure of the injection horizon has most likely been exceeded occasionally, accompanied by increased microseismic activity. Our analysis of 3-D ray tracing for direct and converted phases suggests that one of the event clusters is located at a shallower depth than the reservoir injection interval. However, this event cluster is most likely unrelated to changes in the injection activity at a single well, as the event times do not correlate with the wellhead pressures. Furthermore, this event cluster shows b-values close to one, indicating re-activated natural or tectonic seismicity on pre-existing weakness zones rather than injection induced seismicity. Analysis of event azimuths and significant shear wave splitting of up to 5 per cent provide further valuable insight into fluid migration and fracture orientation at the reservoir level. Although only one geophone was available during the critical injection period, the microseismic monitoring of CO2 injection at In Salah is capable of addressing some of the most relevant questions about fluid migration and reservoir integrity. An improved monitoring array with larger aperture and higher sensitivity is highly recommended, as it could greatly enhance the value of this technique. As such, real-time microseismic monitoring can be used to guide the injection pressure below fracture pressure, thus providing a tool to mitigate the risk of inducing felt seismicity and compromising seal integrity.

Oxygen control of breathing by an olfactory receptor activated by lactate

PubMed Central

Chang, Andy J.; Ortega, Fabian E.; Riegler, Johannes; Madison, Daniel V.; Krasnow, Mark A.

2015-01-01

Summary Animals have evolved homeostatic responses to changes in oxygen availability that act on different time scales. Although the hypoxia-inducible factor (HIF) transcriptional pathway that controls long term responses to low oxygen (hypoxia) has been established1, the pathway that mediates acute responses to hypoxia in mammals is not well understood. Here we show that the olfactory receptor Olfr78 is highly and selectively expressed in oxygen-sensitive glomus cells of the carotid body, a chemosensory organ at the carotid artery bifurcation that monitors blood oxygen and stimulates breathing within seconds when oxygen declines2. Olfr78 mutants fail to increase ventilation in hypoxia but respond normally to hypercapnia. Glomus cells are present in normal numbers and appear structurally intact, but hypoxia-induced carotid body activity is diminished. Lactate, a metabolite that rapidly accumulates in hypoxia and induces hyperventilation3–6, activates Olfr78 in heterologous expression experiments, induces calcium transients in glomus cells, and stimulates carotid sinus nerve activity through Olfr78. We propose that in addition to its role in olfaction, Olfr78 acts as a hypoxia sensor in the breathing circuit by sensing lactate produced when oxygen levels decline. PMID:26560302

Toxicity testing of leachate from waste landfills using medaka (Oryzias latipes) for monitoring environmental safety.

PubMed

Osaki, Kae; Kashiwada, Shosaku; Tatarazako, Norihisa; Ono, Yoshiro

2006-06-01

To investigate the environmental safety of waste disposal landfill sites and of land reclaimed from such sites, we evaluated the toxicity of leachate from these sites by a combination of bioassays in the Japanese killifish medaka Oryzias latipes. We tested for lethal toxicity in adult and larval medaka and for hatching inhibition of embryos from eggs. As biochemical evidence of the effects of leachate exposure, CYP1A (EROD activity) and vitellogenin (Vtg) were induced. We also bioassayed water-treated leachate and downstream river water. Leachate solution was lethal to larval and adult medaka. Embryo hatchability was inhibited, and abnormal hatching, spinal deformity and anisophthalmia occurred in embryos exposed to leachate solution. CYP1A was induced by exposure to leachate solution diluted to 1.0%, and EROD activity was significantly higher than in control. Vtg and unknown proteins were induced in the sera of male medaka exposed to the diluted leachate solution. Conventional water treatments worked effectively to remove toxic compounds but did not work well to remove element ions, including heavy metals. Treated leachate produced neither lethal toxicity nor hatching abnormalities during the exposure period. Fish toxicity tests for leachate would be useful for monitoring the environmental safety of landfill sites.

Capacitance measurements of regulated exocytosis in mouse taste cells.

PubMed

Vandenbeuch, Aurelie; Zorec, Robert; Kinnamon, Sue C

2010-11-03

Exocytosis, consisting of the merger of vesicle and plasma membrane, is a common mechanism used by different types of nucleated cells to release their vesicular contents. Taste cells possess vesicles containing various neurotransmitters to communicate with adjacent taste cells and afferent nerve fibers. However, whether these vesicles engage in exocytosis on a stimulus is not known. Since vesicle membrane merger with the plasma membrane is reflected in plasma membrane area fluctuations, we measured membrane capacitance (C(m)), a parameter linearly related to membrane surface area. To investigate whether taste cells undergo regulated exocytosis, we used the compensated tight-seal whole-cell recording technique to monitor depolarization-induced changes in C(m) in the different types of taste cells. To identify taste cell types, mice expressing green fluorescent protein from the TRPM5 promoter or from the GAD67 promoter were used to discriminate type II and type III taste cells, respectively. Moreover, the cell types were also identified by monitoring their voltage-current properties. The results demonstrate that only type III taste cells show significant depolarization-induced increases in C(m), which were correlated to the voltage-activated calcium currents. The results suggest that type III, but neither type II nor type I cells exhibit depolarization-induced regulated exocytosis to release transmitter and activate gustatory afferent nerve fibers.

Apitherapy products enhance the recovery of CCL4-induced hepatic damages in rats.

PubMed

Saral, Özlem; Yildiz, Oktay; Aliyazicioğlu, Rezzan; Yuluğ, Esin; Canpolat, Sinan; Öztürk, Ferhat; Kolayli, Sevgi

2016-01-05

Our objective was to identify the antioxidant properties of honeybee products from Turkey, chestnut honey, pollen, propolis, and royal jelly, and their hepatoprotective activity against CCl4-induced hepatic damage in rats. Animals were fed with honeybee products for 7 days following CCl4 injection. Development of liver damage and oxidative stress were monitored by measuring the activities of the enzymes alanine transaminase, aspartate transaminase, malondialdehyde, superoxide dismutase, and catalase. Antioxidant capacities of the bee products were identified using FRAP and DPPH assays, as well as by measuring total phenolic and flavonoid contents. The antioxidant activities of the honeybee products were highest in propolis, followed, in order, by pollen, honey, and royal jelly. Despite their different levels of antioxidant capacity, their roles in the prevention of liver damage induced by CCl4 were very similar, which can be explained through their bioavailability to the treated animals. Our results suggest that honey, propolis, pollen, and royal jelly significantly enhanced the healing of CCl4-induced liver damage, partially due to their antioxidant properties and bioavailability.

Iron plaque decreases cadmium accumulation in Oryza sativa L. and serves as a source of iron.

PubMed

Sebastian, A; Prasad, M N V

2016-11-01

Cadmium (Cd) contamination occurs in paddy soils; hence it is necessary to reduce Cd content of rice. Application and mode of action of ferrous sulphate in minimizing Cd in rice was monitored in the present study. Pot culture with Indian rice variety Swarna (MTU 7029) was maintained in Cd-spiked soil containing ferrous sulphates, which is expected to reduce Cd accumulation in rice. Responses in rhizosphere pH, root surface, metal accumulation in plant and molecular physiological processes were monitored. Iron plaque was induced on root surfaces after FeSO4 application and the amount of Fe in plaque reduced with increases in Cd in the soil. Rhizosphere pH decreased during plaque formation and became more acidic due to secretion of organic acids from the roots under Cd treatment. Moreover, iron chelate reductase activity increased with Cd treatment, but in the absence of Cd, activity of this enzyme increased in plaque-induced plants. Cd treatment caused expression of OsYSL18, whereas OsYSL15 was expressed only in roots without iron plaque. Fe content of plants increased during plaque formation, which protected plants from Cd-induced Fe deficiency and metal toxicity. This was corroborated with increased biomass, chlorophyll content and quantum efficiency of photo-synthesis among plaque-induced plants. We conclude that ferrous sulphate-induced iron plaque prevents Cd accumulation and Fe deficiency in rice. Iron released from plaque via organic acid mediated dissolution during Cd stress. © 2016 German Botanical Society and The Royal Botanical Society of the Netherlands.

The flavonoid, fisetin, inhibits UV radiation-induced oxidative stress and the activation of NF-kappaB and MAPK signaling in human lens epithelial cells.

PubMed

Yao, Ke; Zhang, Li; Zhang, Yidong; Ye, PanPan; Zhu, Ning

2008-01-01

Ultraviolet (UV) radiation-induced oxidative stress plays a significant role in the progression of cataracts. This study investigated the photoprotective effect of fisetin on UV radiation-induced oxidative stress in human lens epithelial cells and the possible molecular mechanism involved. SRA01/04 cells exposed to different doses of ultraviolet B (UVB) were cultured with various concentrations of fisetin and subsequently monitored for cell viability by the 4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of fisetin on the generation of reactive oxygen species (ROS) of SRA01/04 cells was determined by flow cytometry. Translocation of nuclear factor kappa-B (NF-kappaB) was examined by immunocytochemistry. Expression of NF-kappaB/P65, inhibiter kappa B (IkappaB), and mitogen activated protein kinase (MAPK) proteins were measured by western blot. Treatment of SRA01/04 cells with fisetin inhibited UVB-induced cell death and the generation of ROS. Fisetin inhibited UVB-induced activation and translocation of NF-kappaB/p65, which was mediated through an inhibition of the degradation and activation of IkappaB. Fisetin also inhibited UVB-induced phosphorylation of the p38 and c-Jun N-terminal kinase (JNK) proteins of the MAPK family at various time points studied. The flavonoid, fisetin, could be useful in attenuation of UV radiation-induced oxidative stress and the activation of NF-kappaB and MAPK signaling in human lens epithelial cells, which suggests that fisetin has a potential protective effect against cataractogenesis.

An experimental approach to improve the Monte Carlo modelling of offline PET/CT-imaging of positron emitters induced by scanned proton beams

NASA Astrophysics Data System (ADS)

Bauer, J.; Unholtz, D.; Kurz, C.; Parodi, K.

2013-08-01

We report on the experimental campaign carried out at the Heidelberg Ion-Beam Therapy Center (HIT) to optimize the Monte Carlo (MC) modelling of proton-induced positron-emitter production. The presented experimental strategy constitutes a pragmatic inverse approach to overcome the known uncertainties in the modelling of positron-emitter production due to the lack of reliable cross-section data for the relevant therapeutic energy range. This work is motivated by the clinical implementation of offline PET/CT-based treatment verification at our facility. Here, the irradiation induced tissue activation in the patient is monitored shortly after the treatment delivery by means of a commercial PET/CT scanner and compared to a MC simulated activity expectation, derived under the assumption of a correct treatment delivery. At HIT, the MC particle transport and interaction code FLUKA is used for the simulation of the expected positron-emitter yield. For this particular application, the code is coupled to externally provided cross-section data of several proton-induced reactions. Studying experimentally the positron-emitting radionuclide yield in homogeneous phantoms provides access to the fundamental production channels. Therefore, five different materials have been irradiated by monoenergetic proton pencil beams at various energies and the induced β+ activity subsequently acquired with a commercial full-ring PET/CT scanner. With the analysis of dynamically reconstructed PET images, we are able to determine separately the spatial distribution of different radionuclide concentrations at the starting time of the PET scan. The laterally integrated radionuclide yields in depth are used to tune the input cross-section data such that the impact of both the physical production and the imaging process on the various positron-emitter yields is reproduced. The resulting cross-section data sets allow to model the absolute level of measured β+ activity induced in the investigated targets within a few per cent. Moreover, the simulated distal activity fall-off positions, representing the central quantity for treatment monitoring in terms of beam range verification, are found to agree within 0.6 mm with the measurements at different initial beam energies in both homogeneous and heterogeneous targets. Based on work presented at the Third European Workshop on Monte Carlo Treatment Planning (Seville, 15-18 May 2012).

Mitogen-activated protein kinase inhibitors suppress prostaglandin F(2alpha)-induced myosin-light chain phosphorylation and contraction in iris sphincter smooth muscle.

PubMed

Yousufzai, S Y; Gao, G; Abdel-Latif, A A

2000-10-27

The purpose of this study was to investigate the potential role of mitogen-activated protein (MAP) kinase in contraction by monitoring MAP kinase phosphorylation (activation) and contraction during agonist stimulation of cat iris sphincter smooth muscle. Changes in tension in response to prostaglandin F(2alpha), latanoprost, a prostaglandin F(2alpha) analog used as an anti-glaucoma drug, and carbachol were recorded isometrically, and MAP kinase activation was monitored by Western blot using a phosphospecific p42/p44 MAP kinase antibody. We found that treatment of the muscle with 2'-Amino-3'-methoxyflavone (PD98059) (10 microM), a specific inhibitor of MAP kinase kinase (MEK), inhibited significantly prostaglandin F(2alpha)- and latanoprost-induced phosphorylation and contraction, but had little effect on those evoked by carbachol. Prostaglandin F(2alpha) increased MAP kinase phosphorylation in a concentration-dependent manner with EC(50) value of 1.1 x 10(-8) M and increased contraction with EC(50) of 0.92 x 10(-9) M. The MAP kinase inhibitors PD98059, Apigenin and 1,4-Diamino-2,3-dicyano-1, 4bis(2-aminophenylthio)butadiene (UO126) inhibited prostaglandin F(2alpha)-induced contraction in a concentration-dependent manner with IC(50) values of 2.4, 3.0 and 4.8 microM, respectively. PD98059 had no effect on prostaglandin F(2alpha)- or on carbachol-stimulated inositol-1,4,5-trisphosphate (IP(3)) production. In contrast, the MAP kinase inhibitor inhibited prostaglandin F(2alpha)-induced myosin-light chain (MLC) phosphorylation, but had no effect on that of carbachol. N-[2-(N-(4-Chloro-cinnamyl)-N-methylaminomethyl)phenyl]-N-[2- hydroxyethyl]-4-methoxybenzenesulfonamide (KN-93) (10 microM), a Ca(2+)-calmodulin-dependent protein kinase inhibitor, and Wortmannin (10 microM), an MLC kinase inhibitor, inhibited significantly (by 80%) prostaglandin F(2alpha)- and carbachol-induced contraction. It can be concluded that in this smooth muscle p42/p44 MAP kinases are involved in the mechanism of prostaglandin F(2alpha)-, but not in that of carbachol, induced contraction. In addition, these data clearly indicate that the stimulation of the iris sphincter with prostaglandin F(2alpha) and carbachol activate two distinct pathways, the MAP kinase pathway and the Ca(2+) mobilization pathway.

Activation of aryl hydrocarbon receptor reduces carbendazim-induced cell death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei, Kuo-Liang

Carbendazim inhibits microtubule assembly, thus blocking mitosis and inhibiting cancer cell proliferation. Accordingly, carbendazim is being explored as an anticancer drug. Data show that carbendazim increased mRNA and protein expressions and promoter activity of CYP1A1. In addition, carbendazim activated transcriptional activity of the aryl hydrocarbon response element, and induced nuclear translocation of the aryl hydrocarbon receptor (AhR), a sign the AhR is activated. Carbendazim-induced CYP1A1 expression was blocked by AhR antagonists, and was abolished in AhR signal-deficient cells. Results demonstrated that carbendazim activated the AhR, thereby stimulating CYP1A1 expression. In order to understand whether AhR-induced metabolic enzymes turn carbendazim intomore » less-toxic metabolites, Hoechst 33342 staining to reveal carbendazim-induced nuclear changes and flow cytometry to reveal the subG{sub 0}/G{sub 1} population were applied to monitor carbendazim-induced cell apoptosis. Carbendazim induced less apoptosis in Hepa-1c1c7 cells than in AhR signal-deficient Hepa-1c1c7 mutant cells. Pretreatment with β-NF, an AhR agonist that highly induces CYP1A1 expression, decreased carbendazim-induced cell death. In addition, the lower the level of AhR was, the lower the vitality present in carbendazim-treated cells, including hepatoma cells and their derivatives with AhR RNA interference, also embryonic kidney cells, bladder carcinoma cells, and AhR signal-deficient Hepa-1c1c7 cells. In summary, carbendazim is an AhR agonist. The toxicity of carbendazim was lower in cells with the AhR signal. This report provides clues indicating that carbendazim is more potent at inducing cell death in tissues without than in those with the AhR signal, an important reference for applying carbendazim in cancer chemotherapy. - Highlights: • Carbendazim induced transcriptional activity of the aryl hydrocarbon response element. • Carbendazim induced nuclear translocation of the aryl hydrocarbon receptor (AhR). • Carbendazim induced the expression of cytochrome P450 (CYP) 1A1, an AhR-targeted gene. • Carbendazim is an AhR agonist. • The activated AhR decreased carbendazim-induced cell toxicity and death.« less

Laser heterodyne detection techniques. [for atmospheric monitoring applications

NASA Technical Reports Server (NTRS)

Menzies, R. T.

1976-01-01

The principles of heterodyne radiometry are examined, taking into account thermal radiation, the Dicke microwave radiometer, photomixing in the infrared, and signal-to-noise considerations. The passive heterodyne radiometer is considered and a description is presented of heterodyne techniques in active monitoring systems. Attention is given to gas emissivities in the infrared, component requirements, experimental heterodyne detection of gases, a comparison of the passive heterodyne radiometer with the Michelson interferometer-spectrometer, airborne monitoring applications, turbulence effects on passive heterodyne radiometry, sensitivity improvements with heterodyning, atmosphere-induced degradation of bistatic system performance, pollutant detection experiments with a bistatic system, and the airborne laser absorption spectrometer. Future improvements in spectral flexibility are also discussed.

Measuring dynamics of Caspase-9 activity in living cells using FRET technique during apoptosis induced by high fluence low-power laser irradiation

NASA Astrophysics Data System (ADS)

Wu, Shengnan; Huang, Lei; Sun, Xuegang; Chu, Jiru

2008-12-01

We investigated the activity of caspase-9 for its role in the regulation of apoptosis induced by high fluence Low-power laser irradiation (HF-LPLI). Using a fluorescence resonance energy transfer (FRET) reporter STAT9, caspase-9 activity was monitored in a noninvasive technique in living human lung adenocarcinoma cells (ASTC-a-1). Under physiological conditions, proteolytic activity of caspase-9 kept invalid in order to prevent the cell undergoing apoptosis. However, HF-LPLI caused a significant decrease of Venus/ECFP ratio, indicating caspase-9 was activated which sustained from 70 minutes to 200 minutes post irradiation. This behavior was familiar with that under staurosporine (STS) treatment, which was used here as a positive control to show a characteristical activation of caspase-9. These results demonstrate that the control of caspase-9 activity is an important mechanism for the regulation of apoptosis triggered by HF-LPLI.

Peripheral blood lymphocytes: a model for monitoring physiological adaptation to high altitude.

PubMed

Mariggiò, Maria A; Falone, Stefano; Morabito, Caterina; Guarnieri, Simone; Mirabilio, Alessandro; Pilla, Raffaele; Bucciarelli, Tonino; Verratti, Vittore; Amicarelli, Fernanda

2010-01-01

Depending on the absolute altitude and the duration of exposure, a high altitude environment induces various cellular effects that are strictly related to changes in oxidative balance. In this study, we used in vitro isolated peripheral blood lymphocytes as biosensors to test the effect of hypobaric hypoxia on seven climbers by measuring the functional activity of these cells. Our data revealed that a 21-day exposure to high altitude (5000 m) (1) increased intracellular Ca(2+) concentration, (2) caused a significant decrease in mitochondrial membrane potential, and (3) despite possible transient increases in intracellular levels of reactive oxygen species, did not significantly change the antioxidant and/or oxidative damage-related status in lymphocytes and serum, assessed by measuring Trolox-equivalent antioxidant capacity, glutathione peroxidase activity, vitamin levels, and oxidatively modified proteins and lipids. Overall, these results suggest that high altitude might cause an impairment in adaptive antioxidant responses. This, in turn, could increase the risk of oxidative-stress-induced cellular damage. In addition, this study corroborates the use of peripheral blood lymphocytes as an easily handled model for monitoring adaptive response to environmental challenge.

Quasi-Liquid Layer Formation on Ice under Stratospheric Conditions

NASA Technical Reports Server (NTRS)

McNeill, V. Faye; Loerting, Thomas; Trout, Bernhardt L.; Molina, Luisa T.; Molina, Mario J.

2004-01-01

Characterization of the interaction of hydrogen chloride (HCl) with ice is essential to understanding at a molecular level the processes responsible for ozone depletion involving polar stratospheric cloud (PSC) particles. To explain the catalytic role PSC particle surfaces play during chlorine activation, we proposed previously that HCl induces the formation of a disordered region on the ice surface, a quasi-liquid layer (QLL), at stratospheric conditions. The QLL is known to exist in pure ice crystals at temperatures near the melting point, but its existence at stratospheric temperatures (-85 C to -70 C) had not been reported yet. We studied the interaction of HCl with ice under stratospheric conditions using the complementary approach of a) ellipsometry to directly monitor the ice surface, using chemical ionization mass spectrometry (CIMS) to monitor the gas phase species present in the ellipsometry experiments, and b) flow-tube experiments with CIMS detection. Here we show that trace amounts of HCl induce QLL formation at stratospheric temperatures, and that the QLL enhances the chlorine-activation reaction of HCl with chlorine nitrate (ClONO2), and also enhances acetic acid (CH3COOH) adsorption.

Use of mixed-function oxygenases to monitor contaminant exposure in wildlife

USGS Publications Warehouse

Rattner, B.A.; Hoffman, D.J.; Marn, C.M.

1989-01-01

This overview examines the utility of mixed-function oxygenase (MFO) enzymes as a bioeffects monitor for wildlife (amphibians, reptiles, birds and mammals) in view of their widespread use as indicators of contaminant exposure in aquatic invertebrates and fish. Phylogenetic trends in MFO activity, toxicological implications of induction and the relationship between contaminant exposure and MFO activity are discussed. Field studies using avian embryos and hatchlings suggest that MFO induction has utility for documenting contaminant exposure; however, findings in adult birds and mammals are equivocal. Age, sex and season are sources of variation that require consideration when undertaking field trials. Further understanding of MFO inducibility among species and application of recently developed analytical techniques including quantification of specific cytochrome P-450 isozymes are warranted.

Reversal of profound and "deep" residual rocuronium-induced neuromuscular blockade by sugammadex: a neurophysiological study.

PubMed

Pavoni, V; Gianesello, L; De Scisciolo, G; Provvedi, E; Horton, D; Barbagli, R; Conti, P; Conti, R; Giunta, F

2012-05-01

Sugammadex is the first of a new class of selective relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade (NMB) induced by the aminosteroid neuromuscular blocking drugs rocuronium and vecuronium. Neuromuscular blocking drugs block the transmission from the peripheral nerve to the muscle units, with reduction and disappearance of the evoked electromyographic activity. Usually, neuromuscular monitoring for the investigational reversal drug is performed by calibrated acceleromyography. The efficacy of sugammadex in reversing profound and "deep" residual rocuronium-induced NMB using myogenic motor evoked potentials (mMEPs) monitoring was evaluated. In this prospective trial, 30 consenting patients undergoing propofol-remifentanil anesthesia for spine surgery were enrolled and divided into two groups: Group 1, reversal of profound NMB (sugammadex 16 mg/Kg, 3 minutes after rocuronium 1.2 mg/Kg) and Group 2, reversal of "deep" residual NMB (sugammadex 4 mg/Kg, 15 minutes after rocuronium 0.6 mg/Kg). Myogenic MEPs registrations of upper and lower limbs and the diaphragm were performed, as well as TOF monitoring. After injection of 4 mg/Kg of sugammadex, the means of recovery time of the basal mMEPs amplitudes (diaphragm, and lower limbs and upper limbs) were 124±9.6, 143±163, 151±207 sec, respectively whereas after 16 mg/Kg of sugammadex the times were 109±13.8, 124±0.6, and 135±14.1 sec. Times to TOF ratio 0.9 were 114±75 and 186±105 sec in Group 1 and 2, respectively. No serious adverse effects related to sugammadex and to electrical stimulation were reported. No reoccurrence of neuromuscular block was observed. Neurophysiological monitoring using mMEPs confirmed that sugammadex provided a complete recovery from profound and "deep" residual rocuronium-induced neuromuscular blockade.

Comparison of automated home-cage monitoring systems: emphasis on feeding behaviour, activity and spatial learning following pharmacological interventions.

PubMed

Robinson, Lianne; Riedel, Gernot

2014-08-30

Different automated systems have been developed to facilitate long-term and continuous assessment of behaviours including locomotor activity, feeding behaviour and circadian activity. This study assessed the effectiveness of three different observation systems as methods for determining strain and pharmacological induced differences in locomotor activity, feeding behaviour and spatial learning. The effect of the CB1 antagonist AM251 on feeding behaviour was determined in the PhenoMaster and PhenoTyper. Next, effects of cholinergic (scopolamine) and glutamatergic (Phenylcyclidine, PCP) receptor antagonism and dopaminergic agonism (apomorphine) on activity were assessed in the PhenoTyper and IntelliCage. Finally, the IntelliCage was utilised to determine differences in activity and spatial learning of C57BL/6 and DBA/2 mouse strains following pharmacological intervention. AM251 induced a suppression of food intake, feeding behaviour and a reduction in body weight in both the PhenoTyper and PhenoMaster. Apomorphine reduced activity in both the PhenoTyper and IntelliCage. Whereas, decreased activity was evident with PCP in the PhenoTyper, but not IntelliCage and Scopolamine induced a trend towards elevated levels of activity in the IntelliCage but not PhenoTyper. Strain differences in activity and spatial learning were also evident, with increased corner visits and drug induced impairments only observed with C57BL/6 mice. The automated home cage observation systems determined similar drug and strain effects on behaviour to those observed using traditional methods. All three observation systems reported drug-induced changes in behaviour however, they differ in their application of spatial learning tasks and utilisation of single versus group housed recordings. Copyright © 2014 Elsevier B.V. All rights reserved.

Radioactivity observed in the sodium iodide gamma-ray spectrometer returned on the Apollo 17 mission

NASA Technical Reports Server (NTRS)

Dyer, C. S.; Trombka, J. I.; Schmadebeck, R. L.; Eller, E.; Bielefeld, M. J.; Okelley, G. D.; Eldridge, J. S.; Northcutt, K. J.; Metzger, A. E.; Reedy, R. C.

1975-01-01

In order to obtain information on radioactive background induced in the Apollo 15 and 16 gamma-ray spectrometers (7 cm x 7 cm NaI) by particle irradiation during spaceflight, and identical detector was flown and returned to earth on the Apollo 17 mission. The induced radioactivity was monitored both internally and externally from one and a half hours after splashdown. When used in conjunction with a computation scheme for estimating induced activation from calculated trapped proton and cosmic-ray fluences, these results show an important contribution resulting from both thermal and energetic neutrons produced in the heavy spacecraft by cosmic-ray interactions.

A REVIEW ON THE RADIATION THERAPY TECHNOLOGIST RECEIVED DOSE FROM INDUCED ACTIVATION IN HIGH-ENERGY MEDICAL LINEAR ACCELERATORS.

PubMed

Nourmohammadi, Bahareh; Mesbahi, Asghar

2018-06-01

Despite all advantages for using high-energy photons for radiotherapy, high-energy photon beams (≥10 MV) induce photonuclear and neutron capture interactions, which result in producing radionuclide byproducts inside the Linac head and bunker, exposing radiation therapy technologists (RTTs) and patients to excessive dose. By the use of higher photon energy, greater number of monitor unit, greater field size and adding treatment accessories, induced dose rate become greater in the isocenter mainly due to activation of high-Z materials inside the Linac head. Activated radionuclides disintegrate with γ, β+ and β- rays with half-lives between 2 min up to more than 5 years. Several researches estimated additional exposure to an RTT depend on treatment strategies, beam energy, and delay time before entrance to the treatment room between 0.1 and 4.9 mSv/y and proposed at least 2 min delay before entrance to the treatment room after treatments with high-energy photon beams.

Experience from a multi-country initiative to improve the monitoring of selected reproductive health indicators in Africa.

PubMed

Barreix, Maria; Tunçalp, Özge; Mutombo, Namuunda; Adegboyega, Ayotunde A; Say, Lale

2017-05-01

Universal access to sexual and reproductive health remains part of the unfinished business of global development in Africa. To achieve it, health interventions should be monitored using programmatic indicators. WHO's Strengthening Measurement of Reproductive Health Indicators in Africa initiative, implemented in Ghana, Nigeria, Kenya, Uganda, and Zimbabwe, aimed to improve national information systems for routine monitoring of reproductive health indicators. Participating countries developed action plans employing a two-pronged strategy: (1) revising, standardizing, and harmonizing existing reproductive health indicators captured through routine information-systems; and (2) building data-collection capacity through training and supervision at select pilot sites. Country teams evaluated existing and new indicators, and outlined barriers to strengthening routine measurement. Activities included updating abortion-care guidelines (spontaneous and induced abortions), providing training on laws surrounding induced abortions, and improving feedback mechanisms. The country teams updated monitoring and evaluation frameworks, and attempted to build recording/reporting capacity in selected pilot areas. Barriers to implementing the initiative that were encountered included restrictive induced-abortion laws, staff turn-over, and administrative delays, including low capacity among healthcare staff and competing priorities for staff time. The areas identified for further improvement were up-scaling programs to a national level, creating scorecards to record data, increasing collaborations with the private sector, conducting related costing exercises, and performing ex-post evaluations. © 2017 World Health Organization; licensed by Wiley on behalf of International Federation of Gynecology and Obstetrics.

Induced seismicity response of hydraulic fracturing: results of a multidisciplinary monitoring at the Wysin site, Poland.

PubMed

López-Comino, J A; Cesca, S; Jarosławski, J; Montcoudiol, N; Heimann, S; Dahm, T; Lasocki, S; Gunning, A; Capuano, P; Ellsworth, W L

2018-06-05

Shale oil and gas exploitation by hydraulic fracturing experienced a strong development worldwide over the last years, accompanied by a substantial increase of related induced seismicity, either consequence of fracturing or wastewater injection. In Europe, unconventional hydrocarbon resources remain underdeveloped and their exploitation controversial. In UK, fracturing operations were stopped after the M w 2.3 Blackpool induced earthquake; in Poland, operations were halted in 2017 due to adverse oil market conditions. One of the last operated well at Wysin, Poland, was monitored independently in the framework of the EU project SHEER, through a multidisciplinary system including seismic, water and air quality monitoring. The hybrid seismic network combines surface mini-arrays, broadband and shallow borehole sensors. This paper summarizes the outcomes of the seismological analysis of these data. Shallow artificial seismic noise sources were detected and located at the wellhead active during the fracturing stages. Local microseismicity was also detected, located and characterised, culminating in two events of M w 1.0 and 0.5, occurring days after the stimulation in the vicinity of the operational well, but at very shallow depths. A sharp methane peak was detected ~19 hours after the M w 0.5 event. No correlation was observed between injected volumes, seismicity and groundwater parameters.

A1 adenosine receptor-induced phosphorylation and modulation of transglutaminase 2 activity in H9c2 cells: A role in cell survival.

PubMed

Vyas, Falguni S; Hargreaves, Alan J; Bonner, Philip L R; Boocock, David J; Coveney, Clare; Dickenson, John M

2016-05-01

The regulation of tissue transglutaminase (TG2) activity by the GPCR family is poorly understood. In this study, we investigated the modulation of TG2 activity by the A1 adenosine receptor in cardiomyocyte-like H9c2 cells. H9c2 cells were lysed following stimulation with the A1 adenosine receptor agonist N(6)-cyclopentyladenosine (CPA). Transglutaminase activity was determined using an amine incorporating and a protein cross linking assay. TG2 phosphorylation was assessed via immunoprecipitation and Western blotting. The role of TG2 in A1 adenosine receptor-induced cytoprotection was investigated by monitoring hypoxia-induced cell death. CPA induced time and concentration-dependent increases in amine incorporating and protein crosslinking activity of TG2. CPA-induced increases in TG2 activity were attenuated by the TG2 inhibitors Z-DON and R283. Responses to CPA were blocked by PKC (Ro 31-8220), MEK1/2 (PD 98059), p38 MAPK (SB 203580) and JNK1/2 (SP 600125) inhibitors and by removal of extracellular Ca(2+). CPA triggered robust increases in the levels of TG2-associated phosphoserine and phosphothreonine, which were attenuated by PKC, MEK1/2 and JNK1/2 inhibitors. Fluorescence microscopy revealed TG2-mediated biotin-X-cadaverine incorporation into proteins and proteomic analysis identified known (Histone H4) and novel (Hexokinase 1) protein substrates for TG2. CPA pre-treatment reversed hypoxia-induced LDH release and decreases in MTT reduction. TG2 inhibitors R283 and Z-DON attenuated A1 adenosine receptor-induced cytoprotection. TG2 activity was stimulated by the A1 adenosine receptor in H9c2 cells via a multi protein kinase dependent pathway. These results suggest a role for TG2 in A1 adenosine receptor-induced cytoprotection. Copyright © 2016 Elsevier Inc. All rights reserved.

FRET analysis demonstrates a rapid activating of caspase-3 during PDT-induced apoptosis

NASA Astrophysics Data System (ADS)

Wu, Yunxia; Chen, Qun

2006-09-01

Apoptosis is a very important cellular event that plays a key role in pathogeny and therapy of many diseases. In this study, a recombinant caspase-3 substrate was used as a fluorescence resonance energy transfer (FRET) probe to detect the activation of caspase-3, and to monitor apoptosis in human lung adenocarcinoma (ASTC-a- 1) cells. With laser scanning confocal microscopy, we found that Photofrin were localized primarily in mitochondria, the primary targets of Photofrin-PDT. By analyzing the dynamic changes of FRET fluorescence, the results indicate that the onset and completion of caspase-3 activation induced by PDT is more rapidly than that by tumor necrosis factor-α (TNF-α). The activation of caspase-3 by PDT started 20 minutes after treatment and completed in about 15 minutes. In comparison, the onset of caspase-3 activation by TNF-a was delayed by 3 hours and the completion of caspase-3 activation required a significantly longer time (approximately 90 minutes). These results indicated that the initiation and process of caspase-3 activation are different corresponding to different treatment methods. Our data suggest that caspase-3 activation mediated by the cell surface death receptors is slower than that of the mitochondrial pathway and the mitochondria is an efficient target to induce apoptosis.

Anaphylaxis Imaging: Non-Invasive Measurement of Surface Body Temperature and Physical Activity in Small Animals

PubMed Central

Manzano-Szalai, Krisztina; Pali-Schöll, Isabella; Krishnamurthy, Durga; Stremnitzer, Caroline; Flaschberger, Ingo; Jensen-Jarolim, Erika

2016-01-01

In highly sensitized patients, the encounter with a specific allergen from food, insect stings or medications may rapidly induce systemic anaphylaxis with potentially lethal symptoms. Countless animal models of anaphylaxis, most often in BALB/c mice, were established to understand the pathophysiology and to prove the safety of different treatments. The most common symptoms during anaphylactic shock are drop of body temperature and reduced physical activity. To refine, improve and objectify the currently applied manual monitoring methods, we developed an imaging method for the automated, non-invasive measurement of the whole-body surface temperature and, at the same time, of the horizontal and vertical movement activity of small animals. We tested the anaphylaxis imaging in three in vivo allergy mouse models for i) milk allergy, ii) peanut allergy and iii) egg allergy. These proof-of-principle experiments suggest that the imaging technology represents a reliable non-invasive method for the objective monitoring of small animals during anaphylaxis over time. We propose that the method will be useful for monitoring diseases associated with both, changes in body temperature and in physical behaviour. PMID:26963393

Insect abundance over Chinese rice fields in relation to environmental parameters, studied with a polarization-sensitive CW near-IR lidar system

NASA Astrophysics Data System (ADS)

Zhu, Shiming; Malmqvist, Elin; Li, Wansha; Jansson, Samuel; Li, Yiyun; Duan, Zheng; Svanberg, Katarina; Feng, Hongqiang; Song, Ziwei; Zhao, Guangyu; Brydegaard, Mikkel; Svanberg, Sune

2017-07-01

Effective monitoring of flying insects is of major societal importance in view of the role of insects as indispensable pollinators, destructive disease vectors and economically devastating agricultural pests. The present paper reports on monitoring of flying agricultural pests using a continuous-wave lidar system in a rice-field location in Southern China. Using a Scheimpflug arrangement, range resolution over several 100 m long observational paths was achieved. The system operates with two perpendicularly polarized near-infrared lasers, which are activated intermittently, and back-scattered radiation from insects was recorded by a linear array detector placed after a linear polarizer. Our polarization sensitive system was used to monitor the flying insect diurnal activity and also the influence of changes in weather conditions, e.g., the occurrence of rain. Activity strongly peaked at dusk and rose again, although to a lower extent, just before dawn. At the onset of rainfall, a strong increase in insect counts occurred which was interpreted as the rain-induced bringing down of high-altitude migrant insects.

A mid-infrared flow-through sensor for label-free monitoring of enzyme inhibition.

PubMed

Armenta, S; Tomischko, W; Lendl, B

2008-12-01

Label-free monitoring of acetylcholinesterase (AChE) activity was achieved with a mid-infrared flow-through sensor. The flow-through sensor comprised agarose beads, carrying covalently immobilized AChE, which were placed in a temperature-controlled (37 degrees C) CaF(2) flow cell with an optical path of 60 mum. The sensor was incorporated into a computer-controlled sequential injection (SI) system for automated liquid handling. Different mixtures of enzyme substrate acetylcholine (ACh) and inhibitor (tacrine) were prepared and fed into the flow-through sensor. The flow was stopped as soon as the prepared mixtures reached the sensor. Enzymatic hydrolysis of ACh by AChE was directly monitored as it took place in the flow-through sensor. The inhibition effect of tacrine was calculated from the reaction-induced spectral changes, revealing an important decrease in the activity of AChE, approaching zero when the inhibitor concentration is high enough. The developed mid-infrared flow-through sensor is flexible and can be used to study the inhibitor activity of different target molecules as well as different enzymes.

Alleviation of salt-induced oxidative damage by 5-aminolevulinic acid in wheat seedlings

NASA Astrophysics Data System (ADS)

Genişel, Mucip; Erdal, Serkan

2016-04-01

The aim of this study was to elucidate how 5-aminolevulinic acid (ALA), the precursor of chlorophyll compounds, affects the defence mechanisms of wheat seedlings induced by salt stress. To determine the possible stimulative effects of ALA against salinity, 11-day old wheat seedlings were sprayed with ALA at two different concentrations (10 and 20 mg.l-1) and then stressed by exposure to salt (150 mM NaCl). The salt stress led to significant changes in the antioxidant activity. While guaiacol peroxidase activity decreased, the activities of superoxide dismutase, catalase, and ascorbate peroxidase markedly increased under salt stress. Compared to the salt stress alone, the application of ALA beforehand further increased the activity of these enzymes. This study is the first time the effects of ALA have been monitored with regard to protein content and the isoenzyme profiles of the antioxidant enzymes. Although the salt stress reduced both the soluble protein content and protein band intensities, pre-treating with ALA significantly mitigated these stress-induced reductions. The data for the isoenzyme profiles of the antioxidant enzymes paralleled that of the ALA-induced increases in antioxidant activity. As a consequence of the high antioxidant activity in the seedlings pre-treated with ALA, the stress-induced elevations in the reactive oxygen species, superoxide anion, and hydrogen peroxide contents and lipid peroxidation levels were markedly diminished. Taken together, this data demonstrated that pre-treating with ALA confers resistance to salt stress by modulating the protein synthesis and antioxidant activity in wheat seedlings.

Activation energy of light induced isomerization of resveratrol.

PubMed

Figueiras, Teresa Sofia; Neves-Petersen, Maria Teresa; Petersen, Steffen B

2011-09-01

Isomerization of trans-stilbenes is known to be induced by light. The two isomers have distinct absorption, fluorescence excitation and emission spectra. Resveratrol, 3,4',5-trihydroxystilbene, is a member of the stilbene family. The interest of the scientific community in resveratrol has increased over the last years due to its biomedical properties. Whereas there is a growing confidence that trans-resveratrol is non-toxic, very little is known about the pharmacology of cis-resveratrol. Of this very reason there is considerable interest in knowing the energetics of the trans-cis conversion. Cis-resveratrol is characterized by a large fluorescence quantum yield when compared to trans-resveratrol. In the present paper we report a detailed analysis of the spectral changes induced in trans-resveratrol upon 260 nm excitation for different time periods. Spectral changes have been monitored with UV-visible absorption and steady-state fluorescence spectroscopy at pH 4 at 20, 25, 30, 35, 40, 45 and 50 °C. Continuous 260 nm excitation induces a blue shift in the absorption and fluorescence excitation spectra of resveratrol and a 14 nm blue shift in its fluorescence emission. The photoisomerization yield is reported as a function of 260 nm excitation time. 330 min continuous excitation led to ~60% isomerization yield. The kinetics of trans-cis isomerization has been monitored following the increase in fluorescence quantum yield upon continuous 260 nm excitation of trans-resveratrol. The study was carried out at the above mentioned temperatures in order to obtain the Arrhenius activation energy of photoisomerization. Activation energy and pre-exponential factor were 3.7 ± 0.3 kcal.mol(-1) and 10.6 ± 1.6 s(-1), respectively. The activation energy is comparable with previously reported values for the photoisomerization of other stilbenes.

Transport via SLC5A8 (SMCT1) Is Obligatory for 2-Oxothiazolidine-4-Carboxylate to Enhance Glutathione Production in Retinal Pigment Epithelial Cells

PubMed Central

Babu, Ellappan; Ananth, Sudha; Veeranan-Karmegam, Rajalakshmi; Coothankandaswamy, Veena; Smith, Sylvia B.; Boettger, Thomas; Ganapathy, Vadivel

2011-01-01

Purpose. To evaluate the role of SLC5A8 in the transport of 2-oxothiazolidine-4-carboxylate (OTC) and to determine whether OTC augments glutathione production in RPE cells, thereby providing protection against oxidative stress. Methods. SLC5A8-mediated transport of OTC was monitored in Xenopus laevis oocytes by electrophysiological means. Saturation kinetics, Na+-activation kinetics, and inhibition by ibuprofen were analyzed by monitoring OTC-induced currents as a measure of transport activity. Oxidative stress was induced in ARPE-19 cells and primary RPE cells isolated from wild type and Slc5a8-/- mouse retinas using H2O2, and the effects of OTC on cell death and intracellular glutathione concentration were examined. Results. Heterologous expression of human SLC5A8 in X. laevis oocytes induced Na+-dependent inward currents in the presence of OTC under voltage-clamp conditions. The transport of OTC via SLC5A8 was saturable, with a Kt of 104 ± 3 μM. The Na+-activation kinetics was sigmoidal with a Hill coefficient of 1.9 ± 0.1, suggesting involvement of two Na+ in the activation process. Ibuprofen, a blocker of SLC5A8, inhibited SLC5A8-mediated OTC transport; the concentration necessary for half-maximal inhibition was 17 ± 1 μM. OTC increased glutathione levels and protected ARPE-19 and primary RPE cells isolated from wild type mouse retinas from H2O2-induced cell death. These effects were abolished in primary RPE isolated from Slc5a8-/- mouse retinas. Conclusions. OTC is a transportable substrate for SLC5A8. OTC augments glutathione production in RPE cells, thereby protecting them from oxidative damage. Transport via SLC5A8 is obligatory for this process. PMID:21508099

Transcranial direct current stimulation and power spectral parameters: a tDCS/EEG co-registration study

PubMed Central

Mangia, Anna L.; Pirini, Marco; Cappello, Angelo

2014-01-01

Transcranial direct current stimulation (tDCS) delivers low electric currents to the brain through the scalp. Constant electric currents induce shifts in neuronal membrane excitability, resulting in secondary changes in cortical activity. Concomitant electroencephalography (EEG) monitoring during tDCS can provide valuable information on the tDCS mechanisms of action. This study examined the effects of anodal tDCS on spontaneous cortical activity in a resting brain to disclose possible modulation of spontaneous oscillatory brain activity. EEG activity was measured in ten healthy subjects during and after a session of anodal stimulation of the postero-parietal cortex to detect the tDCS-induced alterations. Changes in the theta, alpha, beta, and gamma power bands were investigated. Three main findings emerged: (1) an increase in theta band activity during the first minutes of stimulation; (2) an increase in alpha and beta power during and after stimulation; (3) a widespread activation in several brain regions. PMID:25147519

Bispectral index, entropy, and quantitative electroencephalogram during single-agent xenon anesthesia.

PubMed

Laitio, Ruut M; Kaskinoro, Kimmo; Särkelä, Mika O K; Kaisti, Kaike K; Salmi, Elina; Maksimow, Anu; Långsjö, Jaakko W; Aantaa, Riku; Kangas, Katja; Jääskeläinen, Satu; Scheinin, Harry

2008-01-01

The aim was to evaluate the performance of anesthesia depth monitors, Bispectral Index (BIS) and Entropy, during single-agent xenon anesthesia in 17 healthy subjects. After mask induction with xenon and intubation, anesthesia was continued with xenon only. BIS, State Entropy and Response Entropy, and electroencephalogram were monitored throughout induction, steady-state anesthesia, and emergence. The performance of BIS, State Entropy, and Response Entropy were evaluated with prediction probability, sensitivity, and specificity analyses. The power spectrum of the raw electroencephalogram signal was calculated. The mean (SD) xenon concentration during anesthesia was 66.4% (2.4%). BIS, State Entropy, and Response Entropy demonstrated low prediction probability values at loss of response (0.455, 0.656, and 0.619) but 1 min after that the values were high (0.804, 0.941, and 0.929). Thereafter, equally good performance was demonstrated for all indices. At emergence, the prediction probability values to distinguish between steady-state anesthesia and return of response for BIS, State Entropy, and Response Entropy were 0.988, 0.892, and 0.992. No statistical differences between the performances of the monitors were observed. Quantitative electroencephalogram analyses showed generalized increase in total power (P < 0.001), delta (P < 0.001) and theta activity (P < 0.001), and increased alpha activity (P = 0.003) in the frontal brain regions. Electroencephalogram-derived depth of sedation indices BIS and Entropy showed a delay to detect loss of response during induction of xenon anesthesia. Both monitors performed well in distinguishing between conscious and unconscious states during steady-state anesthesia. Xenon-induced changes in electroencephalogram closely resemble those induced by propofol.

Activation of transglutaminase 2 by nerve growth factor in differentiating neuroblastoma cells: A role in cell survival and neurite outgrowth.

PubMed

Algarni, Alanood S; Hargreaves, Alan J; Dickenson, John M

2018-02-05

NGF (nerve growth factor) and tissue transglutaminase (TG2) play important roles in neurite outgrowth and modulation of neuronal cell survival. In this study, we investigated the regulation of TG2 transamidase activity by NGF in retinoic acid-induced differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. TG2 transamidase activity was determined using an amine incorporation and a peptide cross linking assay. In situ TG2 activity was assessed by visualising the incorporation of biotin-X-cadaverine using confocal microscopy. The role of TG2 in NGF-induced cytoprotection and neurite outgrowth was investigated by monitoring hypoxia-induced cell death and appearance of axonal-like processes, respectively. The amine incorporation and protein crosslinking activity of TG2 increased in a time and concentration-dependent manner following stimulation with NGF in N2a and SH-SY5Y cells. NGF mediated increases in TG2 activity were abolished by the TG2 inhibitors Z-DON (Z-ZON-Val-Pro-Leu-OMe; Benzyloxycarbonyl-(6-Diazo-5-oxonorleucinyl)-l-valinyl-l-prolinyl-l-leucinmethylester) and R283 (1,3,dimethyl-2[2-oxo-propyl]thio)imidazole chloride) and by pharmacological inhibition of extracellular signal-regulated kinases 1 and 2 (ERK1/2), protein kinase B (PKB) and protein kinase C (PKC), and removal of extracellular Ca 2+ . Fluorescence microscopy demonstrated NGF induced in situ TG2 activity. TG2 inhibition blocked NGF-induced attenuation of hypoxia-induced cell death and neurite outgrowth in both cell lines. Together, these results demonstrate that NGF stimulates TG2 transamidase activity via a ERK1/2, PKB and PKC-dependent pathway in differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. Furthermore, NGF-induced cytoprotection and neurite outgrowth are dependent upon TG2. These results suggest a novel and important role of TG2 in the cellular functions of NGF. Copyright © 2017 Elsevier B.V. All rights reserved.

A system to investigate the remediation of organic vapors using microwave-induced plasma with fluidized carbon granules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dawson, Elizabeth A.; Parkes, Gareth M. B.; Bond, Gary

This article describes a system to investigate the parameters for the remediation of organic vapors using microwave-induced plasma on fluidized carbon granules. The system is based on a single mode microwave apparatus with a variable power (2.45 GHz) generator. Carbon granules are fluidized in a silica tube situated in the sample section of a waveguide incorporating two additional ports to allow plasma intensity monitoring using a light sensor and imaging with a digital camera. A fluoroptic probe is used for in situ measurement of the carbon granule temperature, while the effluent gas temperature is measured with a thermocouple situated inmore » the silica tube outside the cavity. Data acquisition and control software allow experiments using a variety of microwave power regimes while simultaneously recording the light intensity of any plasma generated within the carbon bed, together with its temperature. Evaluation using two different granular activated carbons and ethyl acetate, introduced as a vapor into the fluidizing air stream at a concentration of 1 ppm, yielded results which indicated that significant destruction of ethyl acetate, as monitored using a mass spectrometer, was achieved only with the carbon granules showing high plasma activity under pulsed microwave conditions. The system is therefore suitable for comparison of the relative microwave activities of various activated carbon granules and their performance in microwave remediation and regeneration.« less

Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees

PubMed Central

1994-01-01

The role of interleukin 6 (IL-6) in the toxic sequelae of sepsis is controversial. To assess the part of IL-6 in inflammatory responses to endotoxin, we investigated eight chimpanzees after either a bolus intravenous injection of Escherichia coli endotoxin (n = 4; 4 ng/kg) or after the same dose of endotoxin with a simultaneous bolus intravenous injection of an anti-IL-6 mAb (30 mg; n = 4). Anti-IL-6 did not affect the induction of the cytokine network (tumor necrosis factor [TNF], soluble TNF receptors types I and II, and IL-8) by endotoxin, nor did it influence the occurrence of a neutrophilic leukocytosis and neutrophil degranulation, as monitored by the measurement of elastase- alpha 1-antitrypsin complexes. In contrast, anti-IL-6 markedly attenuated endotoxin-induced activation of coagulation, monitored with the plasma levels of the prothrombin fragment F1+2 and thrombin- antithrombin III complexes, whereas activation of fibrinolysis, determined with the plasma concentrations of plasmin-alpha 2- antiplasmin complexes, remained unaltered. We conclude that IL-6 does not have a feedback effect on the release of other cytokines after injection of endotoxin, and that it is not involved in endotoxin- induced neutrophilia or neutrophil degranulation. IL-6 is, however, an important intermediate factor in activation of coagulation in low grade endotoxemia in chimpanzees. PMID:8145042

Intrinsic Astrocyte Heterogeneity Influences Tumor Growth in Glioma Mouse Models.

PubMed

Irvin, David M; McNeill, Robert S; Bash, Ryan E; Miller, C Ryan

2017-01-01

The influence of cellular origin on glioma pathogenesis remains elusive. We previously showed that mutations inactivating Rb and Pten and activating Kras transform astrocytes and induce tumorigenesis throughout the adult mouse brain. However, it remained unclear whether astrocyte subpopulations were susceptible to these mutations. We therefore used genetic lineage tracing and fate mapping in adult conditional, inducible genetically engineered mice to monitor transformation of glial fibrillary acidic protein (GFAP) and glutamate aspartate transporter (GLAST) astrocytes and immunofluorescence to monitor cellular composition of the tumor microenvironment over time. Because considerable regional heterogeneity exists among astrocytes, we also examined the influence of brain region on tumor growth. GFAP astrocyte transformation induced uniformly rapid, regionally independent tumor growth, but transformation of GLAST astrocytes induced slowly growing tumors with significant regional bias. Transformed GLAST astrocytes had reduced proliferative response in culture and in vivo and malignant progression was delayed in these tumors. Recruited glial cells, including proliferating astrocytes, oligodendrocyte progenitors and microglia, were the majority of GLAST, but not GFAP astrocyte-derived tumors and their abundance dynamically changed over time. These results suggest that intrinsic astrocyte heterogeneity, and perhaps regional brain microenvironment, significantly contributes to glioma pathogenesis. © 2016 International Society of Neuropathology.

A bioluminescent caspase-1 activity assay rapidly monitors inflammasome activation in cells.

PubMed

O'Brien, Martha; Moehring, Danielle; Muñoz-Planillo, Raúl; Núñez, Gabriel; Callaway, Justin; Ting, Jenny; Scurria, Mike; Ugo, Tim; Bernad, Laurent; Cali, James; Lazar, Dan

2017-08-01

Inflammasomes are protein complexes induced by diverse inflammatory stimuli that activate caspase-1, resulting in the processing and release of cytokines, IL-1β and IL-18, and pyroptosis, an immunogenic form of cell death. To provide a homogeneous method for detecting caspase-1 activity, we developed a bioluminescent, plate-based assay that combines a substrate, Z-WEHD-aminoluciferin, with a thermostable luciferase in an optimized lytic reagent added directly to cultured cells. Assay specificity for caspase-1 is conferred by inclusion of a proteasome inhibitor in the lytic reagent and by use of a caspase-1 inhibitor to confirm activity. This approach enables a specific and rapid determination of caspase-1 activation. Caspase-1 activity is stable in the reagent thereby providing assay convenience and flexibility. Using this assay system, caspase-1 activation has been determined in THP-1 cells following treatment with α-hemolysin, LPS, nigericin, gramicidin, MSU, R848, Pam3CSK4, and flagellin. Caspase-1 activation has also been demonstrated in treated J774A.1 mouse macrophages, bone marrow-derived macrophages (BMDMs) from mice, as well as in human primary monocytes. Caspase-1 activity was not detected in treated BMDMs derived from Casp1 -/- mice, further confirming the specificity of the assay. Caspase-1 activity can be measured directly in cultured cells using the lytic reagent, or caspase-1 activity released into medium can be monitored by assay of transferred supernatant. The caspase-1 assay can be multiplexed with other assays to monitor additional parameters from the same cells, such as IL-1β release or cell death. The caspase-1 assay in combination with a sensitive real-time monitor of cell death allows one to accurately establish pyroptosis. This assay system provides a rapid, convenient, and flexible method to specifically and quantitatively monitor caspase-1 activation in cells in a plate-based format. This will allow a more efficient and effective assessment of inflammasome activation as well as enable high-throughput screening for inflammasome modulators. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Drought onset mechanisms revealed by satellite solar-induced chlorophyll fluorescence: Insights from two contrasting extreme events

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Ying; Fu, Rong; Dickinson, Robert

This study uses the droughts of 2011 in Texas and 2012 over the central Great Plains as case studies to explore the potential of satellite-observed solar-induced chlorophyll fluorescence (SIF) for monitoring drought dynamics. We find that the spatial patterns of negative SIF anomalies from the Global Ozone Monitoring Experiment 2 (GOME-2) closely resembled drought intensity maps from the U.S. Drought Monitor for both events. The drought-induced suppression of SIF occurred throughout 2011 but was exacerbated in summer in the Texas drought. This event was characterized by a persistent depletion of root zone soil moisture caused by yearlong below-normal precipitation. Inmore » contrast, for the central Great Plains drought, warmer temperatures and relatively normal precipitation boosted SIF in the spring of 2012; however, a sudden drop in precipitation coupled with unusually high temperatures rapidly depleted soil moisture through evapotranspiration, leading to a rapid onset of drought in early summer. Accordingly, SIF reversed from above to below normal. For both regions, the GOME-2 SIF anomalies were significantly correlated with those of root zone soil moisture, indicating that the former can potentially be used as proxy of the latter for monitoring agricultural droughts with different onset mechanisms. Further analyses indicate that the contrasting dynamics of SIF during these two extreme events were caused by changes in both fraction of absorbed photosynthetically active radiation fPAR and fluorescence yield, suggesting that satellite SIF is sensitive to both structural and physiological/biochemical variations of vegetation. Here, we conclude that the emerging satellite SIF has excellent potential for dynamic drought monitoring.« less

Drought onset mechanisms revealed by satellite solar-induced chlorophyll fluorescence: Insights from two contrasting extreme events

DOE PAGES

Sun, Ying; Fu, Rong; Dickinson, Robert; ...

2015-11-02

This study uses the droughts of 2011 in Texas and 2012 over the central Great Plains as case studies to explore the potential of satellite-observed solar-induced chlorophyll fluorescence (SIF) for monitoring drought dynamics. We find that the spatial patterns of negative SIF anomalies from the Global Ozone Monitoring Experiment 2 (GOME-2) closely resembled drought intensity maps from the U.S. Drought Monitor for both events. The drought-induced suppression of SIF occurred throughout 2011 but was exacerbated in summer in the Texas drought. This event was characterized by a persistent depletion of root zone soil moisture caused by yearlong below-normal precipitation. Inmore » contrast, for the central Great Plains drought, warmer temperatures and relatively normal precipitation boosted SIF in the spring of 2012; however, a sudden drop in precipitation coupled with unusually high temperatures rapidly depleted soil moisture through evapotranspiration, leading to a rapid onset of drought in early summer. Accordingly, SIF reversed from above to below normal. For both regions, the GOME-2 SIF anomalies were significantly correlated with those of root zone soil moisture, indicating that the former can potentially be used as proxy of the latter for monitoring agricultural droughts with different onset mechanisms. Further analyses indicate that the contrasting dynamics of SIF during these two extreme events were caused by changes in both fraction of absorbed photosynthetically active radiation fPAR and fluorescence yield, suggesting that satellite SIF is sensitive to both structural and physiological/biochemical variations of vegetation. Here, we conclude that the emerging satellite SIF has excellent potential for dynamic drought monitoring.« less

Towards a Solid Foundation of Using Remotely Sensed Solar-Induced Chlorophyll Fluorescence for Crop Monitoring and Yield Forecast

NASA Astrophysics Data System (ADS)

Chen, Y.; Sun, Y.; You, L.; Liu, Y.

2017-12-01

The growing demand for food production due to population increase coupled with high vulnerability to volatile environmental changes poses a paramount challenge for mankind in the coming century. Real-time crop monitoring and yield forecasting must be a key part of any solution to this challenge as these activities provide vital information needed for effective and efficient crop management and for decision making. However, traditional methods of crop growth monitoring (e.g., remotely sensed vegetation indices) do not directly relate to the most important function of plants - photosynthesis and therefore crop yield. The recent advance in the satellite remote sensing of Solar-Induced chlorophyll Fluorescence (SIF), an integrative photosynthetic signal from molecular origin and a direct measure of plant functions holds great promise for real-time monitoring of crop growth conditions and forecasting yields. In this study, we use satellite measurements of SIF from both the Global Ozone Monitoring Experiment-2 (GOME-2) onboard MetOp-A and the Orbiting Carbon Observatory-2 (OCO-2) satellites to estimate crop yield using both process-based and statistical models. We find that SIF-based crop yield well correlates with the global yield product Spatial Production Allocation Model (SPAM) derived from ground surveys for all major crops including maize, soybean, wheat, sorghum, and rice. The potential and challenges of using upcoming SIF satellite missions for crop monitoring and prediction will also be discussed.

Physiological responses induced by pleasant stimuli.

PubMed

Watanuki, Shigeki; Kim, Yeon-Kyu

2005-01-01

The specific physiological responses induced by pleasant stimuli were investigated in this study. Various physiological responses of the brain (encephaloelectrogram; EEG), autonomic nervous system (ANS), immune system and endocrine system were monitored when pleasant stimuli such as odors, emotional pictures and rakugo, a typical Japanese comical story-telling, were presented to subjects. The results revealed that (i) EEG activities of the left frontal brain region were enhanced by a pleasant odor; (ii) emotional pictures related to primitive element such as nudes and erotic couples elevated vasomotor sympathetic nervous activity; and (iii) an increase in secretory immunoglobulin A (s-IgA) and a decrease in salivary cortisol (s-cortisol) were induced by rakugo-derived linguistic pleasant emotion. Pleasant emotion is complicated state. However, by considering the evolutionary history of human being, it is possible to assess and evaluate pleasant emotion from certain physiological responses by appropriately summating various physiological parameters.

Phenyl Saligenin Phosphate Induced Caspase-3 and c-Jun N-Terminal Kinase Activation in Cardiomyocyte-Like Cells.

PubMed

Felemban, Shatha G; Garner, A Christopher; Smida, Fathi A; Boocock, David J; Hargreaves, Alan J; Dickenson, John M

2015-11-16

At present, little is known about the effect(s) of organophosphorous compounds (OPs) on cardiomyocytes. In this study, we have investigated the effects of phenyl saligenin phosphate (PSP), two organophosphorothioate insecticides (diazinon and chlorpyrifos), and their acutely toxic metabolites (diazoxon and chlorpyrifos oxon) on mitotic and differentiated H9c2 cardiomyoblasts. OP-induced cytotoxicity was assessed by monitoring MTT reduction, LDH release, and caspase-3 activity. Cytotoxicity was not observed with diazinon, diazoxon, or chlorpyrifos oxon (48 h exposure; 200 μM). Chlorpyrifos-induced cytotoxicity was only evident at concentrations >100 μM. In marked contrast, PSP displayed pronounced cytotoxicity toward mitotic and differentiated H9c2 cells. PSP triggered the activation of JNK1/2 but not ERK1/2, p38 MAPK, or PKB, suggesting a role for this pro-apoptotic protein kinase in PSP-induced cell death. The JNK1/2 inhibitor SP 600125 attenuated PSP-induced caspase-3 and JNK1/2 activation, confirming the role of JNK1/2 in PSP-induced cytotoxicity. Fluorescently labeled PSP (dansylated PSP) was used to identify novel PSP binding proteins. Dansylated PSP displayed cytotoxicity toward differentiated H9c2 cells. 2D-gel electrophoresis profiles of cells treated with dansylated PSP (25 μM) were used to identify proteins fluorescently labeled with dansylated PSP. Proteomic analysis identified tropomyosin, heat shock protein β-1, and nucleolar protein 58 as novel protein targets for PSP. In summary, PSP triggers cytotoxicity in differentiated H9c2 cardiomyoblasts via JNK1/2-mediated activation of caspase-3. Further studies are required to investigate whether the identified novel protein targets of PSP play a role in the cytotoxicity of this OP, which is usually associated with the development of OP-induced delayed neuropathy.

Nitric oxide (NO.) stabilizes whereas nitrosonium (NO+) enhances filopodial outgrowth by rat retinal ganglion cells in vitro.

PubMed

Cheung, W S; Bhan, I; Lipton, S A

2000-06-16

Recent observations suggest that nitric oxide (NO(.)) can increase or decrease growth cone motility. Here, these apparently paradoxical results are explained by distinct actions of different NO-related species. Filopodial morphology of 223 rat retinal ganglion cells was monitored under computer-enhanced video microscopy in the presence of NO synthase (NOS) substrates or inhibitors, donors of specific NO-related species, and membrane-permeant cyclic nucleotide analogs. Physiological NOS activity induced filopodial outgrowth, whereas inhibition of NOS stabilized filopodia. Similar to NOS, nitrosonium (NO(+) transfer) and peroxynitrite (ONOO(-)), which can regulate the activity of growth-associated proteins by S-nitrosylation and oxidation, respectively, induced filopodial outgrowth. In contrast, NO(.), which stimulates guanylate cyclase to increase cGMP, stabilized filopodial activity. Thus disparate NO-related species may offer a dynamic process of filopodial growth regulation.

Stochastic nature and red cell population distribution of the sickling-induced Ca2+ permeability.

PubMed

Lew, V L; Ortiz, O E; Bookchin, R M

1997-06-01

To explore basic properties of the sickling-induced cation permeability pathway, the Ca2+ component (Psickle-Ca) was studied in density-fractionated sickle cell anemia (SS) discocytes through its effects on the activity of the cells' Ca2+sensitive K+-channels (KCa). The instant state of KCa channel activation was monitored during continuous or cyclic deoxygenation of the cells using a novel thiocyanate-densecell formation method. Each deoxy pulse caused a reversible, sustained Psickle-Ca, which activated KCa channels in only 10-45% of cells at physiological [Ca2+]o ("activated cells"). After removal of cells activated by each previous deoxy pulse, subsequent pulses generated similar activated cell fractions, indicating a random determination rather than the response of a specific vulnerable subpopulation. The fraction of activated cells rose monotonically with [Ca2+]o along a curve reflecting the cells' distribution of Psickle-Ca, with values high enough in a small cell fraction to trigger near-maximal KCa channels. Consistent with the stochastic nature of Psickle-Ca, repeated deoxygenated-oxygenated pulsing led to progressive dense cell formation, whereas single long pulses caused one early density shift. Thus deoxygenation-induced Ca2+-permeabilization in SS cells is a probabilistic event with large cumulative dehydrating potential. The possible molecular nature of Psickle-Ca is discussed.

Analysis of trichloroethylene-induced global DNA hypomethylation in hepatic L-02 cells by liquid chromatography-electrospray ionization tandem mass spectrometry.

PubMed

Zhang, Hang; Hong, Wen-Xu; Ye, Jinbo; Yang, Xifei; Ren, Xiaohu; Huang, Aibo; Yang, Linqing; Zhou, Li; Huang, Haiyan; Wu, Desheng; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun

2014-04-04

Trichloroethylene (TCE), a major occupational and environmental pollutant, has been recently associated with aberrant epigenetic changes in experimental animals and cultured cells. TCE is known to cause severe hepatotoxicity; however, the association between epigenetic alterations and TCE-induced hepatotoxicity are not yet well explored. DNA methylation, catalyzed by enzymes known as DNA methyltransferases (DNMT), is a major epigenetic modification that plays a critical role in regulating many cellular processes. In this study, we analyzed the TCE-induced effect on global DNA methylation and DNMT enzymatic activity in human hepatic L-02 cells. A sensitive and quantitative method combined with liquid chromatography and electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) was validated and utilized for assessing the altered DNA methylation in TCE-induced L-02 cells. Quantification was accomplished in multiple reaction monitoring (MRM) mode by monitoring a transition pair of m/z 242.1 (molecular ion)/126.3 (fragment ion) for 5-mdC and m/z 268.1/152.3 for dG. The correlation coefficient of calibration curves between 5-mdC and dG was higher than 0.9990. The intra-day and inter-day relative standard derivation values (RSD) were on the range of 0.53-7.09% and 0.40-2.83%, respectively. We found that TCE exposure was able to significantly decrease the DNA methylation and inhibit DNMT activity in L-02 cells. Our results not only reveal the association between TCE exposure and epigenetic alterations, but also provide an alternative mass spectrometry-based method for rapid and accurate assessment of chemical-induced altered DNA methylation in mammal cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Stress monitoring versus microseismic ruptures in an active deep mine

NASA Astrophysics Data System (ADS)

Tonnellier, Alice; Bouffier, Christian; Bigarré, Pascal; Nyström, Anders; Österberg, Anders; Fjellström, Peter

2015-04-01

Nowadays, underground mining industry has developed high-technology mass mining methods to optimise the productivity at deep levels. Such massive extraction induces high-level stress redistribution generating seismic events around the mining works, threatening safety and economics. For this reason mining irregular deep ore bodies calls for steadily enhanced scientific practises and technologies to guarantee the mine environment to be safer and stable for the miners and the infrastructures. INERIS, within the framework of the FP7 European project I2Mine and in partnership with the Swedish mining company Boliden, has developed new methodologies in order to monitor both quasi-static stress changes and ruptures in a seismic prone area. To this purpose, a unique local permanent microseismic and stress monitoring network has been installed into the deep-working Garpenberg mine situated to the north of Uppsala (Sweden). In this mine, ore is extracted using sublevel stoping with paste fill production/distribution system and long-hole drilling method. This monitoring network has been deployed between about 1100 and 1250 meter depth. It consists in six 1-component and five 3-component microseismic probes (14-Hz geophones) deployed in the Lappberget area, in addition to three 3D stress monitoring cells that focus on a very local exploited area. Objective is three-fold: to quantify accurately quasi-static stress changes and freshly-induced stress gradients with drift development in the orebody, to study quantitatively those stress changes versus induced detected and located microseismic ruptures, and possibly to identify quasi-static stress transfer from those seismic ruptures. Geophysical and geotechnical data are acquired continuously and automatically transferred to INERIS datacenter through the web. They are made available on a secured web cloud monitoring infrastructure called e.cenaris and completed with mine data. Such interface enables the visualisation of the monitoring data coming from the mine in quasi-real time and facilitates information exchanges and decision making for experts and stakeholders. On the basis of these data acquisition and sharing, preliminary analysis has been started to highlight whether stress variations and seismic sources behaviour might be directly bound with mine working evolution and could improve the knowledge on the equilibrium states inside the mine. Knowing such parameters indeed will be a potential solution to understand better the response of deep mining activities to the exploitation solicitations and to develop, if possible, methods to prevent from major hazards such as rock bursts and other ground failure phenomena.

Identification of HSP70-inducing activity in Arnica montana extract and purification and characterization of HSP70-inducers.

PubMed

Usui, Keiko; Ikeda, Tsuyoshi; Horibe, Yuumi; Nakao, Mitsuyoshi; Hoshino, Tatsuya; Mizushima, Tohru

2015-04-01

The expression of heat shock proteins (HSPs), particularly HSP70, is receiving considerable attention in the field of cosmetics, particularly given our recent report that ultraviolet-induced melanin production, skin damage and wrinkle formation were all suppressed in transgenic mice expressing HSP70. In the present study, we searched for HSP70-inducers from a library of herbal extracts that have already been approved as quasi-pharmaceutical products in Japan. We selected an ethanol extract of Arnica montana (A. montana), based on its high HSP70-inducing activity and low cytotoxicity. Cell viability was determined by MTT method and expression of HPS70 was monitored by immunoblotting analysis. From the extract, we purified and identified eight sesquiterpene lactones (AM1-8) as HSP70-inducers, among which AM-2 (helenalin 2-methylbutyrate) was selected due to its good HSP70-inducing properties and low cytotoxicity. Treatment of cultured mouse melanoma cells with AM-2 or A. montana extract up-regulated the expression of HSP70 in a dose-dependent manner. This treatment also activated heat shock factor-1, a transcription factor for hsp genes. Furthermore, pre-treatment of cells with AM-2 or A. montana extract decreased melanin production and expression and activity of tyrosinase. These results suggest that AM-2 and A. montana extract could be beneficial for use in hypopigmenting cosmetics as a consequence of their stimulatory effects on HSP70 expression. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Blarina brevicauda as a biological monitor of polychlorinated biphenyls: Evaluation of hepatic cytochrome p450 induction

USGS Publications Warehouse

Russell, J.S.; Halbrook, R.S.; Woolf, A.; French, J.B.; Melancon, M.J.

2004-01-01

We assessed the value of short-tailed shrews (Blarina brevicauda) as a possible biomonitor for polychlorinated biphenyl pollution through measurement of the induction of hepatic cytochrome P450 and associated enzyme activities. First, we checked the inducibility of four monooxygenases (benzyloxyresorufin-O-dealkylase [BROD], ethoxyresorufin-O-dealkylase [EROD], methoxyresorufin-O-dealkylase [MROD], and pentoxyresorufin-O-dealkylase [PROD]) by measuring the activity of these enzymes in hepatic microsomes prepared from shrews injected with $-naphthoflavone ($NF) or phenobarbital (PB), typical inducers of cytochrome P4501A (CYP1A) and CYP2B enzyme families, respectively. Enzyme activity was induced in shrews that received $NF but not in shrews that received PB; PROD was not induced by either exposure. Later, shrews were exposed to a mixture of polychlorinated biphenyls (PCBs) (Aroclor 1242:1254, in 1:2 ratio) at 0.6, 9.6, and 150 ppm in food, for 31 d. Induction in these shrews was measured by specific enzyme activity (BROD, EROD, and MROD) in hepatic microsomes, by western blotting of solubilized microsomes against antibodies to CYP1A or CYP2B, and by duration of sodium pentobarbital-induced sleep. These three CYP enzymes were induced in shrews by PCBs at similar levels of exposure as in cotton rat (Sigmodon hispidus). Neither sleep time nor the amount of CYP2B family protein were affected by PCB exposure. Blarina brevicauda can be a useful biomonitor of PCBs that induce CYP1A, especially in habitats where they are the abundant small mammal.

Blarina brevicauda as a biological monitor of polychlorinated biphenyls: evaluation of hepatic cytochrome P450 induction.

PubMed

Russell, Julie S; Halbrook, Richard S; Woolf, Alan; French, John B; Melancon, Mark J

2004-08-01

We assessed the value of short-tailed shrews (Blarina brevicauda) as a possible biomonitor for polychlorinated biphenyl pollution through measurement of the induction of hepatic cytochrome P450 and associated enzyme activities. First, we checked the inducibility of four monooxygenases (benzyloxyresorufin-O-dealkylase [BROD], ethoxyresorufin-O-dealkylase [EROD], methoxyresorufin-O-dealkylase [MROD], and pentoxyresorufin-O-dealkylase [PROD]) by measuring the activity of these enzymes in hepatic microsomes prepared from shrews injected with beta-naphthoflavone (betaNF) or phenobarbital (PB), typical inducers of cytochrome P4501A (CYP1A) and CYP2B enzyme families, respectively. Enzyme activity was induced in shrews that received betaNF but not in shrews that received PB; PROD was not induced by either exposure. Later, shrews were exposed to a mixture of polychlorinated biphenyls (PCBs) (Aroclor 1242:1254, in 1:2 ratio) at 0.6, 9.6, and 150 ppm in food, for 31 d. Induction in these shrews was measured by specific enzyme activity (BROD, EROD, and MROD) in hepatic microsomes, by western blotting of solubilized microsomes against antibodies to CYP1A or CYP2B, and by duration of sodium pentobarbital-induced sleep. These three CYP enzymes were induced in shrews by PCBs at similar levels of exposure as in cotton rat (Sigmodon hispidus). Neither sleep time nor the amount of CYP2B family protein were affected by PCB exposure. Blarina brevicauda can be a useful biomonitor of PCBs that induce CYP1A, especially in habitats where they are the abundant small mammal.

Imaging seizure activity: a combined EEG/EMG-fMRI study in reading epilepsy.

PubMed

Salek-Haddadi, Afraim; Mayer, Thomas; Hamandi, Khalid; Symms, Mark; Josephs, Oliver; Fluegel, Dominique; Woermann, Friedrich; Richardson, Mark P; Noppeney, Uta; Wolf, Peter; Koepp, Matthias J

2009-02-01

To characterize the spatial relationship between activations related to language-induced seizure activity, language processing, and motor control in patients with reading epilepsy. We recorded and simultaneously monitored several physiological parameters [voice-recording, electromyography (EMG), electrocardiography (ECG), electroencephalography (EEG)] during blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in nine patients with reading epilepsy. Individually tailored language paradigms were used to induce and record habitual seizures inside the MRI scanner. Voxel-based morphometry (VBM) was used for structural brain analysis. Reading-induced seizures occurred in six out of nine patients. One patient experienced abundant orofacial reflex myocloni during silent reading in association with bilateral frontal or generalized epileptiform discharges. In a further five patients, symptoms were only elicited while reading aloud with self-indicated events. Consistent activation patterns in response to reading-induced myoclonic seizures were observed within left motor and premotor areas in five of these six patients, in the left striatum (n = 4), in mesiotemporal/limbic areas (n = 4), in Brodmann area 47 (n = 3), and thalamus (n = 2). These BOLD activations were overlapping or adjacent to areas physiologically activated during language and facial motor tasks. No subtle structural abnormalities common to all patients were identified using VBM, but one patient had a left temporal ischemic lesion. Based on the findings, we hypothesize that reflex seizures occur in reading epilepsy when a critical mass of neurons are activated through a provoking stimulus within corticoreticular and corticocortical circuitry subserving normal functions.

Berberine regulates neurite outgrowth through AMPK-dependent pathways by lowering energy status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Jiaqi; Cao, Yuanzhao; Cheng, Kuoyuan

2015-06-10

As a widely used anti-bacterial agent and a metabolic inhibitor as well as AMP-activated protein kinase (AMPK) activator, berberine (BBR) has been shown to cross the blood–brain barrier. Its efficacy has been investigated in various disease models of the central nervous system. Neurite outgrowth is critical for nervous system development and is a highly energy-dependent process regulated by AMPK-related pathways. In the present study, we aimed to investigate the effects of BBR on AMPK activation and neurite outgrowth in neurons. The neurite outgrowth of primary rat cortical neurons at different stages of polarization was monitored after exposure of BBR. Intracellularmore » energy level, AMPK activation and polarity-related pathways were also inspected. The results showed that BBR suppressed neurite outgrowth and affected cytoskeleton stability in the early stages of neuronal polarization, which was mediated by lowered energy status and AMPK activation. Liver kinase B1 and PI3K–Akt–GSK3β signaling pathways were also involved. In addition, mitochondrial dysfunction and endoplasmic reticulum stress contributed to the lowered energy status induced by BBR. This study highlighted the knowledge of the complex activities of BBR in neurons and corroborated the significance of energy status during the neuronal polarization. - Highlights: • BBR inhibited neurite outgrowth in early stages of neuronal development. • Lowered neuronal energy status was induced by BBR treatment. • Neuronal energy stress induced by BBR activated AMPK-related pathways. • BBR induced mitochondrial dysfunction and endoplasmic reticulum stress.« less

Transition metal sensing by Toll-like receptor-4: next to nickel, cobalt and palladium are potent human dendritic cell stimulators.

PubMed

Rachmawati, Dessy; Bontkes, Hetty J; Verstege, Marleen I; Muris, Joris; von Blomberg, B Mary E; Scheper, Rik J; van Hoogstraten, Ingrid M W

2013-06-01

Nickel was recently identified as a potent activator of dendritic cells through ligating with human Toll-like receptor (TLR)-4. Here, we studied an extended panel of transition metals neighbouring nickel in the periodic table of elements, for their capacity to activate human monocyte-derived dendritic cells (MoDCs). The panel included chromium, cobalt, and palladium, all of which are known to be frequent clinical sensitizers. MoDC activation was monitored by assessment of release of the pro-inflammatory mediator interleukin (IL)-8, a major downstream result of TLR ligation. Results The data obtained in the present study show that cobalt and palladium also have potent MoDC-activating capacities, whereas copper and zinc, but not iron and chromium, have low but distinct MoDC-activating potential. Involvement of endotoxin contamination in MoDC activation was excluded by Limulus assays and consistent stimulation in the presence of polymyxin B. The critical role of TLR4 in nickel-induced, cobalt-induced and palladium-induced activation was confirmed by essentially similar stimulatory patterns obtained in an HEK293 TLR4/MD2 transfectant cell line. Given the adjuvant role of costimulatory danger signals, the development of contact allergies to the stimulatory metals may be facilitated by signals from direct TLR4 ligation, whereas other metal sensitizers, such as chromium, may rather depend on microbial or tissue-derived cofactors to induce clinical sensitization. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Combined passive detection and ultrafast active imaging of cavitation events induced by short pulses of high-intensity ultrasound.

PubMed

Gateau, Jérôme; Aubry, Jean-François; Pernot, Mathieu; Fink, Mathias; Tanter, Mickaël

2011-03-01

The activation of natural gas nuclei to induce larger bubbles is possible using short ultrasonic excitations of high amplitude, and is required for ultrasound cavitation therapies. However, little is known about the distribution of nuclei in tissues. Therefore, the acoustic pressure level necessary to generate bubbles in a targeted zone and their exact location are currently difficult to predict. To monitor the initiation of cavitation activity, a novel all-ultrasound technique sensitive to single nucleation events is presented here. It is based on combined passive detection and ultrafast active imaging over a large volume using the same multi-element probe. Bubble nucleation was induced using a focused transducer (660 kHz, f-number = 1) driven by a high-power electric burst (up to 300 W) of one to two cycles. Detection was performed with a linear array (4 to 7 MHz) aligned with the single-element focal point. In vitro experiments in gelatin gel and muscular tissue are presented. The synchronized passive detection enabled radio-frequency data to be recorded, comprising high-frequency coherent wave fronts as signatures of the acoustic emissions linked to the activation of the nuclei. Active change detection images were obtained by subtracting echoes collected in the unnucleated medium. These indicated the appearance of stable cavitating regions. Because of the ultrafast frame rate, active detection occurred as quickly as 330 μs after the high-amplitude excitation and the dynamics of the induced regions were studied individually.

Combined passive detection and ultrafast active imaging of cavitation events induced by short pulses of high-intensity ultrasound

PubMed Central

Gateau, Jérôme; Aubry, Jean-François; Pernot, Mathieu; Fink, Mathias; Tanter, Mickaël

2011-01-01

The activation of natural gas nuclei to induce larger bubbles is possible using short ultrasonic excitations of high amplitude, and is required for ultrasound cavitation therapies. However, little is known about the distribution of nuclei in tissues. Therefore, the acoustic pressure level necessary to generate bubbles in a targeted zone and their exact location are currently difficult to predict. In order to monitor the initiation of cavitation activity, a novel all-ultrasound technique sensitive to single nucleation events is presented here. It is based on combined passive detection and ultrafast active imaging over a large volume and with the same multi-element probe. Bubble nucleation was induced with a focused transducer (660kHz, f#=1) driven by a high power (up to 300 W) electric burst of one to two cycles. Detection was performed with a linear array (4–7MHz) aligned with the single-element focal point. In vitro experiments in gelatin gel and muscular tissue are presented. The synchronized passive detection enabled radio-frequency data to be recorded, comprising high-frequency coherent wave fronts as signatures of the acoustic emissions linked to the activation of the nuclei. Active change detection images were obtained by subtracting echoes collected in the unucleated medium. These indicated the appearance of stable cavitating regions. Thanks to the ultrafast frame rate, active detection occurred as soon as 330 μs after the high amplitude excitation and the dynamics of the induced regions were studied individually. PMID:21429844

Detection of system failures in multi-axes tasks. [pilot monitored instrument approach

NASA Technical Reports Server (NTRS)

Ephrath, A. R.

1975-01-01

The effects of the pilot's participation mode in the control task on his workload level and failure detection performance were examined considering a low visibility landing approach. It is found that the participation mode had a strong effect on the pilot's workload, the induced workload being lowest when the pilot acted as a monitoring element during a coupled approach and highest when the pilot was an active element in the control loop. The effects of workload and participation mode on failure detection were separated. The participation mode was shown to have a dominant effect on the failure detection performance, with a failure in a monitored (coupled) axis being detected significantly faster than a comparable failure in a manually controlled axis.

Microseismic monitoring of Chocolate Bayou Texas: the Pleasant Bayou No. 2 geopressured/geothermal energy test-well program. 1981 annual progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mauk, F.J.

1982-01-01

To investigate normal ambient seismicity as well as potentially enhanced seismic activity induced by brine production, a seismic monitoring program has been conducted in the vicinity of the Chocolate Bayou geopressured test well (the Pleasant Bayou No. 2) since September 1978. The Pleasant Bayou No. 2 well has been completed and perforated at depths of 14,467-14,707 feet (4464.4-4482.7m). The brines produced from the Pleasant Bayou No. 2 well are reinjected at a depth of 6226-6538 feet (1897.7-1992.8m) in the Pleasant Bayou No. 1 well. The seismic monitoring network and results obtained from January through November 1981 are described.

Behavioral and Neurochemical Effects of Alpha-Lipoic Acid in the Model of Parkinson's Disease Induced by Unilateral Stereotaxic Injection of 6-Ohda in Rat

PubMed Central

de Araújo, Dayane Pessoa; De Sousa, Caren Nádia Soares; Araújo, Paulo Victor Pontes; Menezes, Carlos Eduardo de Souza; Sousa Rodrigues, Francisca Taciana; Escudeiro, Sarah Souza; Lima, Nicole Brito Cortez; Patrocínio, Manoel Claúdio Azevedo; Aguiar, Lissiana Magna Vasconcelos; Viana, Glauce Socorro de Barros; Vasconcelos, Silvânia Maria Mendes

2013-01-01

This study aimed to investigate behavioral and neurochemical effects of α-lipoic acid (100 mg/kg or 200 mg/kg) alone or associated with L-DOPA using an animal model of Parkinson's disease induced by stereotaxic injection of 6-hydroxydopamine (6-OHDA) in rat striatum. Motor behavior was assessed by monitoring body rotations induced by apomorphine, open field test and cylinder test. Oxidative stress was accessed by determination of lipid peroxidation using the TBARS method, concentration of nitrite and evaluation of catalase activity. α-Lipoic acid decreased body rotations induced by apomorphine, as well as caused an improvement in motor performance by increasing locomotor activity in the open field test and use of contralateral paw (in the opposite side of the lesion produced by 6-OHDA) at cylinder test. α-lipoic acid showed antioxidant effects, decreasing lipid peroxidation and nitrite levels and interacting with antioxidant system by decreasing of endogenous catalase activity. Therefore, α-lipoic acid prevented the damage induced by 6-OHDA or by chronic use of L-DOPA in dopaminergic neurons, suggesting that α-lipoic could be a new therapeutic target for Parkinson's disease prevention and treatment. PMID:24023579

Gastric Electrical Stimulation Decreases Gastric Distension-Induced Central Nociception Response through Direct Action on Primary Afferents

PubMed Central

Ouelaa, Wassila; Ghouzali, Ibtissem; Langlois, Ludovic; Fetissov, Serguei; Déchelotte, Pierre; Ducrotté, Philippe; Leroi, Anne Marie; Gourcerol, Guillaume

2012-01-01

Background & Aims Gastric electrical stimulation (GES) is an effective therapy to treat patients with chronic dyspepsia refractory to medical management. However, its mechanisms of action remain poorly understood. Methods Gastric pain was induced by performing gastric distension (GD) in anesthetized rats. Pain response was monitored by measuring the pseudo-affective reflex (e.g., blood pressure variation), while neuronal activation was determined using c-fos immunochemistry in the central nervous system. Involvement of primary afferents was assessed by measuring phosphorylation of ERK1/2 in dorsal root ganglia. Results GES decreased blood pressure variation induced by GD, and prevented GD-induced neuronal activation in the dorsal horn of the spinal cord (T9–T10), the nucleus of the solitary tract and in CRF neurons of the hypothalamic paraventricular nucleus. This effect remained unaltered within the spinal cord when sectioning the medulla at the T5 level. Furthermore, GES prevented GD-induced phosphorylation of ERK1/2 in dorsal root ganglia. Conclusions GES decreases GD-induced pain and/or discomfort likely through a direct modulation of gastric spinal afferents reducing central processing of visceral nociception. PMID:23284611

DOE Office of Scientific and Technical Information (OSTI.GOV)

MadanKumar, Perumal; NaveenKumar, Perumal; Manikandan, Samidurai

The anti-fibrotic effect of morin was examined in LX-2 cells (culture-activated human hepatic stellate cells) and in diethylnitrosamine induced rat model of liver fibrosis. The in vitro study was designed to determine whether morin affects the survival of cultured LX-2 cells, while the in vivo study was designed to evaluate the antioxidant and anti-fibrotic efficacy of morin on diethylnitrosamine induced liver fibrosis in male albino Wistar rat. The activities of liver function enzymes in serum, liver lipid peroxide levels, activities of serum antioxidant enzymes and liver architecture were monitored to cast light on the antioxidant and hepatoprotective nature of morin.more » To establish the anti-fibrotic effects of morin, the levels of key Wnt signaling molecules which are strongly associated with the signal transduction pathway of HSC activation were measured. Overall, from the in vitro results, it was observed that morin at 50 μM concentration inhibited the proliferation of cultured LX-2 cells, inhibited Wnt signaling and induced G1 cell cycle arrest. The in vivo results further confirmed that morin by downregulating the expressions of GSK-3β, β-catenin and cyclin D1 ameliorated DEN-induced liver fibrosis. Hence morin could be employed as a promising chemopreventive natural supplement for liver fibrosis. - Highlights: • In vivo and in vitro results revealed the active participation of Wnt signaling. • Morin at 50 μM inhibited LX-2 cell proliferation by suppressing Wnt signaling. • Morin exhibited hepatoprotective effects against DEN induced liver fibrosis. • Morin inhibited HSC activation in vivo by downregulating Wnt/β-catenin signaling.« less

Regulatory mechanisms of betacellulin in CXCL8 production from lung cancer cells

PubMed Central

2014-01-01

Background Betacellulin (BTC), a member of the epidermal growth factor (EGF) family, binds and activates ErbB1 and ErbB4 homodimers. BTC was expressed in tumors and involved in tumor growth progression. CXCL8 (interleukin-8) was involved in tumor cell proliferation via the transactivation of the epidermal growth factor receptor (EGFR). Materials and methods The present study was designed to investigate the possible interrelation between BTC and CXCL8 in human lung cancer cells (A549) and demonstrated the mechanisms of intracellular signals in the regulation of both functions. Bio-behaviors of A549 were assessed using Cell-IQ Alive Image Monitoring System. Results We found that BTC significantly increased the production of CXCL8 through the activation of the EGFR-PI3K/Akt-Erk signal pathway. BTC induced the resistance of human lung cancer cells to TNF-α/CHX-induced apoptosis. Treatments with PI3K inhibitors, Erk1/2 inhibitor, or Erlotinib significantly inhibited BTC-induced CXCL8 production and cell proliferation and movement. Conclusion Our data indicated that CXCL8 production from lung cancer cells could be initiated by an autocrine mechanism or external sources of BTC through the EGFR–PI3K–Akt–Erk pathway to the formation of inflammatory microenvironment. BTC may act as a potential target to monitor and improve the development of lung cancer inflammation. PMID:24629040

Biomarker evaluation of skeletal muscle toxicity following clofibrate administration in rats.

PubMed

Bodié, Karen; Buck, Wayne R; Pieh, Julia; Liguori, Michael J; Popp, Andreas

2016-05-01

The use of sensitive biomarkers to monitor skeletal muscle toxicity in preclinical toxicity studies is important for the risk assessment in humans during the development of a novel compound. Skeletal muscle toxicity in Sprague Dawley Rats was induced with clofibrate at different dose levels for 7 days to compare standard clinical pathology assays with novel skeletal muscle and cardiac muscle biomarkers, gene expression and histopathological changes. The standard clinical pathology assays aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) enzyme activity were compared to novel biomarkers fatty acid binding protein 3 (Fabp3), myosin light chain 3 (Myl3), muscular isoform of CK immunoreactivity (three isoforms CKBB, CKMM, CKMB), parvalbumin (Prv), skeletal troponin I (sTnI), cardiac troponin T (cTnT), cardiac troponin I (cTnI), CKMM, and myoglobin (Myo). The biomarker elevations were correlated to histopathological findings detected in several muscles and gene expression changes. Clofibrate predominantly induced skeletal muscle toxicity of type I fibers of low magnitude. Useful biomarkers for skeletal muscle toxicity were AST, Fabp3, Myl3, (CKMB) and sTnI. Measurements of CK enzyme activity by a standard clinical assay were not useful for monitoring clofibrate-induced skeletal muscle toxicity in the rat at the doses used in this study. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

Modulation of transglutaminase 2 activity in H9c2 cells by PKC and PKA signalling: a role for transglutaminase 2 in cytoprotection

PubMed Central

Almami, Ibtesam; Dickenson, John M; Hargreaves, Alan J; Bonner, Philip L R

2014-01-01

BACKGROUND AND PURPOSE Tissue transglutaminase (TG2) has been shown to mediate cell survival in many cell types. In this study, we investigated whether the role of TG2 in cytoprotection was mediated by the activation of PKA and PKC in cardiomyocyte-like H9c2 cells. EXPERIMENTAL APPROACH H9c2 cells were extracted following stimulation with phorbol-12-myristate-13-acetate (PMA) and forskolin. Transglutaminase activity was determined using an amine incorporating and a protein crosslinking assay. The presence of TG isoforms (TG1, 2, 3) was determined using Western blot analysis. The role of TG2 in PMA- and forskolin-induced cytoprotection was investigated by monitoring H2O2-induced oxidative stress in H9c2 cells. KEY RESULTS Western blotting showed TG2 >> TG1 protein expression but no detectable TG3. The amine incorporating activity of TG2 in H9c2 cells increased in a time and concentration-dependent manner following stimulation with PMA and forskolin. PMA and forskolin-induced TG2 activity was blocked by PKC (Ro 31-8220) and PKA (KT 5720 and Rp-8-Cl-cAMPS) inhibitors respectively. The PMA- and forskolin-induced increases in TG2 activity were attenuated by the TG2 inhibitors Z-DON and R283. Immunocytochemistry revealed TG2-mediated biotin-X-cadaverine incorporation into proteins and proteomic analysis identified known (β-tubulin) and novel (α-actinin) protein substrates for TG2. Pretreatment with PMA and forskolin reversed H2O2-induced decrease in MTT reduction and release of LDH. TG2 inhibitors R283 and Z-DON blocked PMA- and forskolin-induced cytoprotection. CONCLUSIONS AND IMPLICATIONS TG2 activity was stimulated via PKA- and PKC-dependent signalling pathways in H9c2 cells These results suggest a role for TG2 in cytoprotection induced by these kinases. PMID:24821315

Excitation functions of nuclear reactions induced by alpha particles up to 42 MeV on natTi for monitoring purposes and TLA

NASA Astrophysics Data System (ADS)

Hermanne, A.; Sonck, M.; Takács, S.; Szelecsényi, F.; Tárkányi, F.

1999-05-01

Excitation functions for the reactions induced by alpha particles on natTi foils and leading to the formation of 44m,44g,46,47,48Sc; 48,51Cr and 48V were determined using the stacked foil technique for energies from the respective reaction thresholds up to 42 MeV. The new experimental values are compared to earlier literature values and generally good accordance is found. It appears that the natTi(α,x) 51Cr reaction is particularly useful for monitoring α-beams in the 10-20 MeV region while for energies above 20 MeV the natTi(α,x) 47Sc reaction or the natTi(α,x) 48V reaction are more suited. The excitation functions established can be used to determine calibration curves for thin layer activation (TLA) as well.

Monitoring nitric oxide (NO) in rat locus coeruleus: differential effects of NO synthase inhibitors.

PubMed

Desvignes, C; Robert, F; Vachette, C; Chouvet, G; Cespuglio, R; Renaud, B; Lambás-Señas, L

1997-04-14

A porphyrinic microsensor combined with in vivo voltammetry was used to monitor extracellular nitric oxide (NO) in the locus coeruleus (LC) of anaesthetized rats. Administration of N omega-nitro-L-arginine p-nitro-anilide (100 mg/kg, i.p) or 7-nitro indazole (30 mg/kg, i.p.), which both inhibit preferentially neuronal NO synthase (NOS), induced a marked decrease in the NO oxidation peak height. On the other hand, N omega-nitro-L-arginine methyl ester (L-NAME) (200 mg/kg, i.p.), a less selective NOS inhibitor, failed to decrease the NO signal. Moreover, intra LC administration of NMDA, known to activate LC noradrenergic neurones, increased the NO signal. This study demonstrates the usefulness of in vivo voltammetry to monitor basal levels of NO and their changes in the LC. Differential effects of NOS inhibitors show that their central activity need to be assessed through in situ measurement of NO before using these inhibitors as neuropharmacological tools.

Caspase-mediated apoptosis induction in zebrafish cerebellar Purkinje neurons.

PubMed

Weber, Thomas; Namikawa, Kazuhiko; Winter, Barbara; Müller-Brown, Karina; Kühn, Ralf; Wurst, Wolfgang; Köster, Reinhard W

2016-11-15

The zebrafish is a well-established model organism in which to study in vivo mechanisms of cell communication, differentiation and function. Existing cell ablation methods are either invasive or they rely on the cellular expression of prokaryotic enzymes and the use of antibiotic drugs as cell death-inducing compounds. We have recently established a novel inducible genetic cell ablation system based on tamoxifen-inducible Caspase 8 activity, thereby exploiting mechanisms of cell death intrinsic to most cell types. Here, we prove its suitability in vivo by monitoring the ablation of cerebellar Purkinje cells (PCs) in transgenic zebrafish that co-express the inducible caspase and a fluorescent reporter. Incubation of larvae in tamoxifen for 8 h activated endogenous Caspase 3 and cell death, whereas incubation for 16 h led to the near-complete loss of PCs by apoptosis. We observed synchronous cell death autonomous to the PC population and phagocytosing microglia in the cerebellum, reminiscent of developmental apoptosis in the forebrain. Thus, induction of apoptosis through targeted activation of caspase by tamoxifen (ATTAC TM ) further expands the repertoire of genetic tools for conditional interrogation of cellular functions. © 2016. Published by The Company of Biologists Ltd.

Melanopsin resets circadian rhythms in cells by inducing clock gene Period1

NASA Astrophysics Data System (ADS)

Yamashita, Shuhei; Uehara, Tomoe; Matsuo, Minako; Kikuchi, Yo; Numano, Rika

2014-02-01

The biochemical, physiological and behavioral processes are under the control of internal clocks with the period of approximately 24 hr, circadian rhythms. The expression of clock gene Period1 (Per1) oscillates autonomously in cells and is induced immediately after a light pulse. Per1 is an indispensable member of the central clock system to maintain the autonomous oscillator and synchronize environmental light cycle. Per1 expression could be detected by Per1∷luc and Per1∷GFP plasmid DNA in which firefly luciferase and Green Fluorescence Protein were rhythmically expressed under the control of the mouse Per1 promoter in order to monitor mammalian circadian rhythms. Membrane protein, MELANOPSIN is activated by blue light in the morning on the retina and lead to signals transduction to induce Per1 expression and to reset the phase of circadian rhythms. In this report Per1 induction was measured by reporter signal assay in Per1∷luc and Per1∷GFP fibroblast cell at the input process of circadian rhythms. To the result all process to reset the rhythms by Melanopsin is completed in single cell like in the retina projected to the central clock in the brain. Moreover, the phase of circadian rhythm in Per1∷luc cells is synchronized by photo-activated Melanopsin, because the definite peak of luciferase activity in one dish was found one day after light illumination. That is an available means that physiological circadian rhythms could be real-time monitor as calculable reporter (bioluminescent and fluorescent) chronological signal in both single and groups of cells.

Optically triggering spatiotemporally confined GPCR activity in a cell and programming neurite initiation and extension

PubMed Central

Karunarathne, W. K. Ajith; Giri, Lopamudra; Kalyanaraman, Vani; Gautam, N.

2013-01-01

G-protein–coupled receptor (GPCR) activity gradients evoke important cell behavior but there is a dearth of methods to induce such asymmetric signaling in a cell. Here we achieved reversible, rapidly switchable patterns of spatiotemporally restricted GPCR activity in a single cell. We recruited properties of nonrhodopsin opsins—rapid deactivation, distinct spectral tuning, and resistance to bleaching—to activate native Gi, Gq, or Gs signaling in selected regions of a cell. Optical inputs were designed to spatiotemporally control levels of second messengers, IP3, phosphatidylinositol (3,4,5)-triphosphate, and cAMP in a cell. Spectrally selective imaging was accomplished to simultaneously monitor optically evoked molecular and cellular response dynamics. We show that localized optical activation of an opsin-based trigger can induce neurite initiation, phosphatidylinositol (3,4,5)-triphosphate increase, and actin remodeling. Serial optical inputs to neurite tips can refashion early neuron differentiation. Methods here can be widely applied to program GPCR-mediated cell behaviors. PMID:23479634

The zinc spark is an inorganic signature of human egg activation.

PubMed

Duncan, Francesca E; Que, Emily L; Zhang, Nan; Feinberg, Eve C; O'Halloran, Thomas V; Woodruff, Teresa K

2016-04-26

Egg activation refers to events required for transition of a gamete into an embryo, including establishment of the polyspermy block, completion of meiosis, entry into mitosis, selective recruitment and degradation of maternal mRNA, and pronuclear development. Here we show that zinc fluxes accompany human egg activation. We monitored calcium and zinc dynamics in individual human eggs using selective fluorophores following activation with calcium-ionomycin, ionomycin, or hPLCζ cRNA microinjection. These egg activation methods, as expected, induced rises in intracellular calcium levels and also triggered the coordinated release of zinc into the extracellular space in a prominent "zinc spark." The ability of the gamete to mount a zinc spark response was meiotic-stage dependent. Moreover, chelation of intracellular zinc alone was sufficient to induce cell cycle resumption and transition of a meiotic cell into a mitotic one. Together, these results demonstrate critical functions for zinc dynamics and establish the zinc spark as an extracellular marker of early human development.

The zinc spark is an inorganic signature of human egg activation

PubMed Central

Duncan, Francesca E.; Que, Emily L.; Zhang, Nan; Feinberg, Eve C.; O’Halloran, Thomas V.; Woodruff, Teresa K.

2016-01-01

Egg activation refers to events required for transition of a gamete into an embryo, including establishment of the polyspermy block, completion of meiosis, entry into mitosis, selective recruitment and degradation of maternal mRNA, and pronuclear development. Here we show that zinc fluxes accompany human egg activation. We monitored calcium and zinc dynamics in individual human eggs using selective fluorophores following activation with calcium-ionomycin, ionomycin, or hPLCζ cRNA microinjection. These egg activation methods, as expected, induced rises in intracellular calcium levels and also triggered the coordinated release of zinc into the extracellular space in a prominent “zinc spark.” The ability of the gamete to mount a zinc spark response was meiotic-stage dependent. Moreover, chelation of intracellular zinc alone was sufficient to induce cell cycle resumption and transition of a meiotic cell into a mitotic one. Together, these results demonstrate critical functions for zinc dynamics and establish the zinc spark as an extracellular marker of early human development. PMID:27113677

Crocin, the main active saffron constituent, mitigates dichlorvos-induced oxidative stress and apoptosis in HCT-116 cells.

PubMed

Ben Salem, Intidhar; Boussabbeh, Manel; Kantaoui, Hiba; Bacha, Hassen; Abid-Essefi, Salwa

2016-08-01

The protective effects of Crocin (CRO), a carotenoid with wide spectrum of pharmacological effects, against the cytotoxicity and the apoptosis produced by exposure to Dichlorvos (DDVP) in HCT116 cells were investigated in this work. The cytotoxicity was monitored by cell viability, ROS generation, antioxidant enzymes activities, malondialdehyde (MDA) production and DNA fragmentation. The apoptosis was assessed through the measurement of the mitochondrial transmembrane potential (ΔΨm) and caspases activation. The results indicated that pretreatment of HCT116 cells with CRO, 2h prior to DDVP exposure, significantly increased the survival of cells, inhibited the ROS generation, modulated the activities of catalase (CAT) and superoxide dismutase (SOD) and reduced the MDA level. The reduction in mitochondrial membrane potential, DNA fragmentation and caspases activation were also inhibited by CRO. These findings suggest that CRO can protect HCT116 cells from DDVP-induced oxidative stress and apoptosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Heparin-induced thrombocytopenia: real-world issues.

PubMed

Linkins, Lori-Ann; Warkentin, Theodore E

2011-09-01

Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating antibodies. HIT sera often activate platelets without needing heparin-such heparin-"independent" platelet activation can be associated with HIT beginning or worsening despite stopping heparin ("delayed-onset HIT"). We address important issues in HIT diagnosis and therapy, using a recent cohort of HIT patients to illustrate influences of heparin type; triggers for HIT investigation; serological features of heparin-independent platelet activation; and treatment. In our cohort of recent HIT cases ( N = 13), low-molecular-weight heparin (dalteparin) was a common causative agent ( N = 8, 62%); most patients were diagnosed after HIT-thrombosis had occurred; and danaparoid was the most frequently selected treatment. Heparin-independent platelet activation was common (7/13 [54%]) and predicted slower platelet count recovery (>1 week) among evaluable patients (5/5 vs 1/6; P = 0.015). In our experience with argatroban-treated patients, HIT-associated consumptive coagulopathy confounds anticoagulant monitoring. Our observations provide guidance on practical aspects of HIT diagnosis and management. Thieme Medical Publishers.

Hydraulic Fracturing Induced Seismicity at Preese Hall, UK: Moment Tensors, Uncertainties and Implications for Microseismic Monitoring Strategies

NASA Astrophysics Data System (ADS)

O'toole, T. B.; Woodhouse, J. H.; Verdon, J.; Kendall, J.

2012-12-01

Hydraulic fracturing operations carried out in April and May 2011 by Cuadrilla Resources Ltd. during the exploration of a shale gas reservoir at Preese Hall, near Blackpool, UK, induced a series of microseismic events. The largest of these, with magnitude ML = 2.3, was felt at the surface and recorded by the British Geological Survey regional seismic network. Subsequently, two local seismic stations were installed, which continued to detect seismicity with ML ≤ 1.5 until the hydraulic fracture treatment was suspended due to the anomalously large magnitudes of the induced earthquakes. Here, we present the results of moment tensor inversions of seismic waveforms recorded by these two near-field stations. We determine the best point source description of an event by minimising the least-squares difference between observed and synthetic waveforms. In contrast to source mechanisms obtained from body wave polarity and amplitude picks, which require a good sampling of the focal sphere and typically assume a pure double-couple mechanism, using the whole waveform allows us to place good constraints on the moment tensor even when only a few seismograms are available, and also enables the investigation of possible non-double-couple components and volume changes associated with a source. We discuss our results in the context of the studies commissioned by Cuadrilla after the suspension of hydraulic fracturing operations at Preese Hall. Using synthetic waveform data, we investigate how different monitoring geometries can be used to reduce uncertainties in source parameters of induced microseisms. While our focus is on the monitoring of hydraulic fracturing operations, the methods developed here are general and could equally be applied to determine moment tensors from surface and borehole observations of seismicity induced by other activities.

Microseismic data records fault activation before and after a Mw 4.1 induced earthquake

NASA Astrophysics Data System (ADS)

Eyre, T.; Eaton, D. W. S.

2017-12-01

Several large earthquakes (Mw 4) have been observed in the vicinity of the town of Fox Creek, Alberta. These events have been determined to be induced earthquakes related to hydraulic fracturing in the region. The largest of these has a magnitude Mw = 4.1, and is associated with a hydraulic-fracturing treatment close to Crooked Lake, about 30 km west of Fox Creek. The underlying factors that lead to localization of the high numbers of hydraulic fracturing induced events in this area remain poorly understood. The treatment that is associated with the Mw 4.1 event was monitored by 93 shallow three-level borehole arrays of sensors. Here we analyze the temporal and spatial evolution of the microseismic and seismic data recorded during the treatment. Contrary to expected microseismic event clustering parallel to the principal horizontal stress (NE - SW), the events cluster along obvious fault planes that align both NNE - SSW and N - S. As the treatment well is oriented N - S, it appears that each stage of the treatment intersects a new portion of the fracture network, causing seismicity to occur. Focal-plane solutions support a strike-slip failure along these faults, with nodal planes aligning with the microseismic cluster orientations. Each fault segment is activated with a cluster of microseismicity in the centre, gradually extending along the fault as time progresses. Once a portion of a fault is active, further seismicity can be induced, regardless if the present stage is distant from the fault. However, the large events seem to occur in regions with a gap in the microseismicity. Interestingly, most of the seismicity is located above the reservoir, including the larger events. Although a shallow-well array is used, these results are believed to have relatively high depth resolution, as the perforation shots are correctly located with an average error of 26 m in depth. This information contradicts previously held views that large induced earthquakes occur primarily, or even exclusively, in the underlying crystalline basement. The findings can give new insights into the dynamics of induced seismicity related to hydraulic fracturing. Additionally, real-time microseismic monitoring can be used to track the evolution of fault activation as it occurs, and can potentially indicate that large events are possible.

River Induced Wellbore Flow Dynamics in Long-Screen Wells and their Impact on Aqueous Sampling Results

NASA Astrophysics Data System (ADS)

Vermeul, V.; McKinley, J. P.; Newcomer, D.; Fritz, B. G.; Mackley, R.; Zachara, J. M.

2010-12-01

Previously published field investigations and modeling studies have demonstrated the potential for sample bias associated with vertical wellbore flow in conventional monitoring wells constructed with long-screened intervals. In this study, simultaneous measurement of 1) wellbore flow using an electromagnetic borehole flowmeter (EBF), 2) depth discrete hydraulic head, and 3) aqueous uranium concentrations were used to quantify wellbore flow and assess the associated impacts on measured aqueous concentrations. Monitoring results demonstrate the utility of continuous (i.e., hourly measurements for ~ one month) ambient wellbore flow monitoring and show that relatively large wellbore flows (up to 4 LPM) can be induced by aquifer hydrodynamics associated with a fluctuating river boundary located approximately 250 m from the test well. The observed vertical wellbore flows were strongly correlated with fluctuations in river stage, alternating between upward and downward flow throughout the monitoring period in response to changes in river stage. Continuous monitoring of ambient wellbore flows using an EBF system allowed these effects to be evaluated in concert with continuously monitored river stage elevations (hourly) and aqueous uranium concentrations (daily) in a long-screen well and an adjacent multi-level well cluster. This study demonstrates that when contaminant concentrations within the aquifer vary significantly over the depth interval interrogated, river-induced vertical wellbore flow can result in variations in measured concentration that nearly encompass the full range of variation in aquifer contaminant concentration with depth. In addition, observed variability in aqueous concentrations measured during active tracer transport experiments provided additional evidence of wellbore flow impacts and showed that the magnitude and direction of wellbore flow varied spatially across the wellfield. An approach to mitigate these effects based on increasing hydraulic resistance within the wellbore was evaluated. This research is part of the ERSP Hanford IFRC at Pacific Northwest National Laboratory.

Improving the monitoring of crop productivity using spaceborne solar-induced fluorescence.

PubMed

Guan, Kaiyu; Berry, Joseph A; Zhang, Yongguang; Joiner, Joanna; Guanter, Luis; Badgley, Grayson; Lobell, David B

2016-02-01

Large-scale monitoring of crop growth and yield has important value for forecasting food production and prices and ensuring regional food security. A newly emerging satellite retrieval, solar-induced fluorescence (SIF) of chlorophyll, provides for the first time a direct measurement related to plant photosynthetic activity (i.e. electron transport rate). Here, we provide a framework to link SIF retrievals and crop yield, accounting for stoichiometry, photosynthetic pathways, and respiration losses. We apply this framework to estimate United States crop productivity for 2007-2012, where we use the spaceborne SIF retrievals from the Global Ozone Monitoring Experiment-2 satellite, benchmarked with county-level crop yield statistics, and compare it with various traditional crop monitoring approaches. We find that a SIF-based approach accounting for photosynthetic pathways (i.e. C3 and C4 crops) provides the best measure of crop productivity among these approaches, despite the fact that SIF sensors are not yet optimized for terrestrial applications. We further show that SIF provides the ability to infer the impacts of environmental stresses on autotrophic respiration and carbon-use-efficiency, with a substantial sensitivity of both to high temperatures. These results indicate new opportunities for improved mechanistic understanding of crop yield responses to climate variability and change. © 2015 John Wiley & Sons Ltd.

Improving the Monitoring of Crop Productivity Using Spaceborne Solar-Induced Fluorescence

NASA Technical Reports Server (NTRS)

Guan, Kaiyu; Berry, Joseph A.; Zhang, Yongguang; Joiner, Joanna; Guanter, Luis; Badgley, Grayson; Lobell, David B.

2015-01-01

Large-scale monitoring of crop growth and yield has important value for forecasting food production and prices and ensuring regional food security. A newly emerging satellite retrieval, solar-induced fluorescence (SIF) of chlorophyll, provides for the first time a direct measurement related to plant photosynthetic activity (i.e. electron transport rate). Here, we provide a framework to link SIF retrievals and crop yield, accounting for stoichiometry, photosynthetic pathways, and respiration losses. We apply this framework to estimate United States crop productivity for 2007-2012, where we use the spaceborne SIF retrievals from the Global Ozone Monitoring Experiment-2 satellite, benchmarked with county-level crop yield statistics, and compare it with various traditional crop monitoring approaches. We find that a SIF-based approach accounting for photosynthetic pathways (i.e. C3 and C4 crops) provides the best measure of crop productivity among these approaches, despite the fact that SIF sensors are not yet optimized for terrestrial applications. We further show that SIF provides the ability to infer the impacts of environmental stresses on autotrophic respiration and carbon-use-efficiency, with a substantial sensitivity of both to high temperatures. These results indicate new opportunities for improved mechanistic understanding of crop yield responses to climate variability and change.

Stimulus-Induced Rhythmic, Periodic, or Ictal Discharges (SIRPIDs).

PubMed

Johnson, Emily L; Kaplan, Peter W; Ritzl, Eva K

2018-05-01

Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) are a relatively common phenomenon found on prolonged electroencephalogram (EEG) monitoring that captures state changes and stimulation of critically ill patients. Common causes include hypoxic injury, traumatic brain injury, and hemorrhage, as well as toxic-metabolic disturbances. Some studies have shown an association between SIRPIDs and the presence of spontaneous electrographic seizures. Although the degree to which SIRPIDs should be treated with antiepileptic medications is unknown, the rare cases of functional imaging obtained in patients with SIRPIDs have not shown an increase in cerebral blood flow to suggest an active ictal process. Stimulus-induced rhythmic, periodic, or ictal discharges may reflect dysregulation of thalamo-cortical projections into abnormal or hyperexcitable cortex.

Anticoagulant and Antiplatelet Activities of Artemisia princeps Pampanini and Its Bioactive Components.

PubMed

Ryu, Ri; Jung, Un Ju; Kim, Hye-Jin; Lee, Wonhwa; Bae, Jong-Sup; Park, Yong Bok; Choi, Myung-Sook

2013-09-01

Artemisia princeps Pampanini (AP) has been used as a traditional medicine in Korea, China and Japan and reported to exhibit various beneficial biological effects including anti-inflammatory, antioxidant, anti-atherogenic and lipid lowering activities; however, its antiplatelet and anticoagulant properties have not been studied. In the present study, we evaluated the effects of an ethanol extract of Artemisia princeps Pampanini (EAP) and its major flavonoids, eupatilin and jaceosidin, on platelet aggregation and coagulation. To determine the antiplatelet activity, arachidonic acid (AA)-, collagen- and ADP (adenosine diphosphate)-induced platelet aggregation were examined along with serotonin and thromboxane A2 (TXA2) generation in vitro. The anticoagulant activity was determined by monitoring the activated partial thromboplastin time (aPTT) and prothrombin time (PT) in vitro. The data showed that EAP and its major flavonoids, eupatilin and jaceosidin, significantly reduced AA-induced platelet aggregation and the generation of serotonin and TXA2, although no significant change in platelet aggregation induced by collagen and ADP was observed. Moreover, EAP significantly prolonged the PT and aPTT. The PT and/or aPTT were significantly increased in the presence of eupatilin and jaceosidin. Thus, these results suggest that EAP may have the potential to prevent or improve thrombosis by inhibiting platelet activation and blood coagulation.

Anticoagulant and Antiplatelet Activities of Artemisia princeps Pampanini and Its Bioactive Components

PubMed Central

Ryu, Ri; Jung, Un Ju; Kim, Hye-jin; Lee, Wonhwa; Bae, Jong-Sup; Park, Yong Bok; Choi, Myung-Sook

2013-01-01

Artemisia princeps Pampanini (AP) has been used as a traditional medicine in Korea, China and Japan and reported to exhibit various beneficial biological effects including anti-inflammatory, antioxidant, anti-atherogenic and lipid lowering activities; however, its antiplatelet and anticoagulant properties have not been studied. In the present study, we evaluated the effects of an ethanol extract of Artemisia princeps Pampanini (EAP) and its major flavonoids, eupatilin and jaceosidin, on platelet aggregation and coagulation. To determine the antiplatelet activity, arachidonic acid (AA)-, collagen- and ADP (adenosine diphosphate)-induced platelet aggregation were examined along with serotonin and thromboxane A2 (TXA2) generation in vitro. The anticoagulant activity was determined by monitoring the activated partial thromboplastin time (aPTT) and prothrombin time (PT) in vitro. The data showed that EAP and its major flavonoids, eupatilin and jaceosidin, significantly reduced AA-induced platelet aggregation and the generation of serotonin and TXA2, although no significant change in platelet aggregation induced by collagen and ADP was observed. Moreover, EAP significantly prolonged the PT and aPTT. The PT and/or aPTT were significantly increased in the presence of eupatilin and jaceosidin. Thus, these results suggest that EAP may have the potential to prevent or improve thrombosis by inhibiting platelet activation and blood coagulation. PMID:24471130

Imposed glutathione-mediated redox switch modulates the tobacco wound-induced protein kinase and salicylic acid-induced protein kinase activation state and impacts on defence against Pseudomonas syringae

PubMed Central

Matern, Sanja; Peskan-Berghoefer, Tatjana; Gromes, Roland; Kiesel, Rebecca Vazquez; Rausch, Thomas

2015-01-01

The role of the redox-active tripeptide glutathione in plant defence against pathogens has been studied extensively; however, the impact of changes in cellular glutathione redox potential on signalling processes during defence reactions has remained elusive. This study explored the impact of elevated glutathione content on the cytosolic redox potential and on early defence signalling at the level of mitogen-activated protein kinases (MAPKs), as well as on subsequent defence reactions, including changes in salicylic acid (SA) content, pathogenesis-related gene expression, callose depositions, and the hypersensitive response. Wild-type (WT) Nicotiana tabacum L. and transgenic high-glutathione lines (HGL) were transformed with the cytosol-targeted sensor GRX1-roGFP2 to monitor the cytosolic redox state. Surprisingly, HGLs displayed an oxidative shift in their cytosolic redox potential and an activation of the tobacco MAPKs wound-induced protein kinase (WIPK) and SA-induced protein kinase (SIPK). This activation occurred in the absence of any change in free SA content, but was accompanied by constitutively increased expression of several defence genes. Similarly, rapid activation of MAPKs could be induced in WT tobacco by exposure to either reduced or oxidized glutathione. When HGL plants were challenged with adapted or non-adapted Pseudomonas syringae pathovars, the cytosolic redox shift was further amplified and the defence response was markedly increased, showing a priming effect for SA and callose; however, the initial and transient hyperactivation of MAPK signalling was attenuated in HGLs. The results suggest that, in tobacco, MAPK and SA signalling may operate independently, both possibly being modulated by the glutathione redox potential. Possible mechanisms for redox-mediated MAPK activation are discussed. PMID:25628332

Palmar skin conductance variability and the relation to stimulation, pain and the motor activity assessment scale in intensive care unit patients.

PubMed

Günther, Anders C; Bottai, Matteo; Schandl, Anna R; Storm, Hanne; Rossi, Patrik; Sackey, Peter V

2013-03-19

Many intensive care unit (ICU) patients describe pain and other adverse feelings that may impact long-term psychological morbidity. Sympathetically mediated palmar skin conductance variability is related to emotionally induced perspiration and correlates with pain levels in the perioperative setting but has not been studied in ICU patients. Twenty non-intubated and 20 intubated general ICU patients were included in this observational study. Patients were monitored with the MED-STORM Pain Monitoring System®. The number of skin conductance fluctuations per second (NSCF) was measured in parallel with bedside observation during one hour of intensive care, including rest, procedures and patient-staff interactions. Arousal-agitation level was monitored with the motor activity assessment scale (MAAS). Pain was monitored with the numeric rating scale (0 to 10) in patients able to communicate or by observation in patients unable to communicate. In non-intubated patients, NSCF increased with increasing stimulation/pain but also with higher MAAS (P=0.002). An interaction effect was found, with increased NSCF response to stimulation/pain with increasing MAAS (P<0.001). In critically ill patients, NSCF may be more useful evaluating emotional distress rather than pain alone. It needs to be assessed whether NSCF monitoring is clinically useful and whether controlling emotional distress with the aid of such monitoring may impact on patient care and outcomes.

Fatigue crack monitoring with coupled piezoelectric film acoustic emission sensors

NASA Astrophysics Data System (ADS)

Zhou, Changjiang

Fatigue-induced cracking is a commonly seen problem in civil infrastructures reaching their original design life. A number of high-profile accidents have been reported in the past that involved fatigue damage in structures. Such incidences often happen without prior warnings due to lack of proper crack monitoring technique. In order to detect and monitor the fatigue crack, acoustic emission (AE) technique, has been receiving growing interests recently. AE can provide continuous and real-time monitoring data on damage progression in structures. Piezoelectric film AE sensor measures stress-wave induced strain in ultrasonic frequency range and its feasibility for AE signal monitoring has been demonstrated recently. However, extensive work in AE monitoring system development based on piezoelectric film AE sensor and sensor characterization on full-scale structures with fatigue cracks, have not been done. A lack of theoretical formulations for understanding the AE signals also hinders the use of piezoelectric film AE sensors. Additionally, crack detection and source localization with AE signals is a very important area yet to be explored for this new type of AE sensor. This dissertation presents the results of both analytical and experimental study on the signal characteristics of surface stress-wave induced AE strain signals measured by piezoelectric film AE sensors in near-field and an AE source localization method based on sensor couple theory. Based on moment tensor theory, generalized expression for AE strain signal is formulated. A special case involving the response of piezoelectric film AE sensor to surface load is also studied, which could potentially be used for sensor calibration of this type of sensor. A new concept of sensor couple theory based AE source localization technique is proposed and validated with both simulated and experimental data from fatigue test and field monitoring. Two series of fatigue tests were conducted to perform fatigue crack monitoring on large-scale steel test specimens using piezoelectric film AE sensors. Continuous monitoring of fatigue crack growth in steel structures is demonstrated in these fatigue test specimens. The use of piezoelectric film AE sensor for field monitoring of existing fatigue crack is also demonstrated in a real steel I-girder bridge located in Maryland. The sensor couple theory based AE source localization is validated using a limited number of piezoelectric film AE sensor data from both fatigue test specimens and field monitoring bridge. Through both laboratory fatigue test and field monitoring of steel structures with active fatigue cracks, the signal characteristics of piezoelectric film AE sensor have been studied in real-world environment.

THE CAFETERIA DIET INCREASES FAT MASS AND CHRONICALLY ELEVATES LUMBAR SYMPATHETIC NERVE ACTIVITY IN RATS

PubMed Central

Muntzel, Martin S.; Al-Naimi, Omar Ali S.; Barclay, Alicia; Ajasin, David

2012-01-01

Obesity causes sympathetic activation that promotes atherosclerosis, end-organ damage, and hypertension. Because high-fat induced weight gain in rats elevates plasma leptin at 1–3 days following onset of calorie dense diets, we hypothesized that diet-induced overfeeding will increase sympathetic activity within one week following onset of the regimen. To test this, we continuously measured sympathetic activity and blood pressure before and during the onset of diet-induced obesity using a high calorie cafeteria-style diet. Female Wistar rats, in which radiotelemeters had been implanted for continuous monitoring of lumbar sympathetic activity, mean arterial pressure, and heart rate, were randomly assigned to groups that received regular chow (control) or a cafeteria diet for a period of 15 days. This short-term cafeteria-feeding regimen caused modest but non-significant increases in body weight (P = 0.07) and a doubling of brown and white adipose tissue (P < 0.01). The increases in fat mass were accompanied by elevations in plasma leptin (P < 0.001) but no change in glucose. Overall heart rates and blood pressure were higher in cafeteria rats compared with controls (P < 0.05). Cafeteria diet-induced weight gain caused increases in lumbar sympathetic nerve activity that became significant by the 12th day of the diet (p < 0.001). These data show, for the first time, that the high-fat cafeteria-style diet stimulates sustained increases in lumbar sympathetic neural drive in rats. PMID:23090774

Assessment of ground-based monitoring techniques applied to landslide investigations

NASA Astrophysics Data System (ADS)

Uhlemann, S.; Smith, A.; Chambers, J.; Dixon, N.; Dijkstra, T.; Haslam, E.; Meldrum, P.; Merritt, A.; Gunn, D.; Mackay, J.

2016-01-01

A landslide complex in the Whitby Mudstone Formation at Hollin Hill, North Yorkshire, UK is periodically re-activated in response to rainfall-induced pore-water pressure fluctuations. This paper compares long-term measurements (i.e., 2009-2014) obtained from a combination of monitoring techniques that have been employed together for the first time on an active landslide. The results highlight the relative performance of the different techniques, and can provide guidance for researchers and practitioners for selecting and installing appropriate monitoring techniques to assess unstable slopes. Particular attention is given to the spatial and temporal resolutions offered by the different approaches that include: Real Time Kinematic-GPS (RTK-GPS) monitoring of a ground surface marker array, conventional inclinometers, Shape Acceleration Arrays (SAA), tilt meters, active waveguides with Acoustic Emission (AE) monitoring, and piezometers. High spatial resolution information has allowed locating areas of stability and instability across a large slope. This has enabled identification of areas where further monitoring efforts should be focused. High temporal resolution information allowed the capture of 'S'-shaped slope displacement-time behaviour (i.e. phases of slope acceleration, deceleration and stability) in response to elevations in pore-water pressures. This study shows that a well-balanced suite of monitoring techniques that provides high temporal and spatial resolutions on both measurement and slope scale is necessary to fully understand failure and movement mechanisms of slopes. In the case of the Hollin Hill landslide it enabled detailed interpretation of the geomorphological processes governing landslide activity. It highlights the benefit of regularly surveying a network of GPS markers to determine areas for installation of movement monitoring techniques that offer higher resolution both temporally and spatially. The small sensitivity of tilt meter measurements to translational movements limited the ability to record characteristic 'S'-shaped landslide movements at Hollin Hill, which were identified using SAA and AE measurements. This high sensitivity to landslide movements indicates the applicability of SAA and AE monitoring to be used in early warning systems, through detecting and quantifying accelerations of slope movement.

Identification of plant compounds that inactivate Shiga toxin from Escherichia coli O157:H7

USDA-ARS?s Scientific Manuscript database

In the present study, we describe a simple cell-based assay for the detection of Stxs and inhibitors of Stx activity. A Vero cell line that expresses a destabilized variant (t1/2 = 2 hours) of the enhanced green fluorescent protein (d2EGFP) was used to monitor the Stx-induced inhibition of protein ...

α-Iso-cubebenol inhibits inflammation-mediated neurotoxicity and amyloid beta 1-42 fibril-induced microglial activation.

PubMed

Park, Sun Young; Park, Tae Gyeong; Lee, Sang-Joon; Bae, Yoe-Sik; Ko, Min J; Choi, Young-Whan

2014-01-01

To examine the antineuroinflammatory and neuroprotective activity of α-iso-cubebenol and its molecular mechanism of action in amyloid β (Aβ) 1-42 fibril-stimulated microglia. Aβ 1-42 fibrils were used to induce a neuroinflammatory response in murine primary microglia and BV-2 murine microglia cell lines. Cell viability was monitored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, protein expression and phosphorylation were determined by Western blot analysis, and matrix metalloproteinase-9 (MMP-9) activity was determined by gelatin zymography assay. In addition, prostaglandin E2 (PGE2), pro-inflammatory cytokines and chemokines were measured by ELISA, and the transactivity of nuclear factor (NF)-κB was determined by a reporter assay. α-Iso-cubebenol significantly inhibited Aβ 1-42 fibril-induced MMP-9, inducible nitric oxide synthase and cyclooxygenase-2 expressions and activity, without affecting cell viability. α-Iso-cubebenol also suppressed the production of tumour necrosis factor-α, IL-1β, IL-6, monocyte chemoattractant protein-1 and reactive oxygen species in a dose-dependent manner, while decreasing the nuclear translocation and transactivity of NF-κB by inhibiting the phosphorylation and degradation of the inhibitor of κB (IκB)α. α-Iso-cubebenol suppressed the phosphorylation of mitogen-activated protein kinase (MAPK) in Aβ 1-42 fibril-stimulated microglia. Primary cortical neurons were protected by the inhibitory effect of α-iso-cubebenol on Aβ 1-42 fibril-induced neuroinflammatory response. α-Iso-cubebenol suppresses Aβ 1-42 fibril-induced neuroinflammatory molecules in primary microglia via the suppression of NF-κB/inhibitor of κBα and MAPK. Importantly, the antineuroinflammatory potential of α-iso-cubebenol is critical for neuroprotection. © 2013 Royal Pharmaceutical Society.

Two-photon-based photoactivation in live zebrafish embryos.

PubMed

Russek-Blum, Niva; Nabel-Rosen, Helit; Levkowitz, Gil

2010-12-24

Photoactivation of target compounds in a living organism has proven a valuable approach to investigate various biological processes such as embryonic development, cellular signaling and adult physiology. In this respect, the use of multi-photon microscopy enables quantitative photoactivation of a given light responsive agent in deep tissues at a single cell resolution. As zebrafish embryos are optically transparent, their development can be monitored in vivo. These traits make the zebrafish a perfect model organism for controlling the activity of a variety of chemical agents and proteins by focused light. Here we describe the use of two-photon microscopy to induce the activation of chemically caged fluorescein, which in turn allows us to follow cell's destiny in live zebrafish embryos. We use embryos expressing a live genetic landmark (GFP) to locate and precisely target any cells of interest. This procedure can be similarly used for precise light induced activation of proteins, hormones, small molecules and other caged compounds.

Potential hazard due to induced radioactivity secondary to radiotherapy: the report of task group 136 of the American Association of Physicists in Medicine.

PubMed

Thomadsen, Bruce; Nath, Ravinder; Bateman, Fred B; Farr, Jonathan; Glisson, Cal; Islam, Mohammad K; LaFrance, Terry; Moore, Mary E; George Xu, X; Yudelev, Mark

2014-11-01

External-beam radiation therapy mostly uses high-energy photons (x-rays) produced by medical accelerators, but many facilities now use proton beams, and a few use fast-neutron beams. High-energy photons offer several advantages over lower-energy photons in terms of better dose distributions for deep-seated tumors, lower skin dose, less sensitivity to tissue heterogeneities, etc. However, for beams operating at or above 10 MV, some of the materials in the accelerator room and the radiotherapy patient become radioactive due primarily to photonuclear reactions and neutron capture, exposing therapy staff and patients to unwanted radiation dose. Some recent advances in radiotherapy technology require treatments using a higher number of monitor units and monitor-unit rates for the same delivered dose, and compared to the conventional treatment techniques and fractionation schemes, the activation dose to personnel can be substantially higher. Radiotherapy treatments with proton and neutron beams all result in activated materials in the treatment room. In this report, the authors review critically the published literature on radiation exposures from induced radioactivity in radiotherapy. They conclude that the additional exposure to the patient due to induced radioactivity is negligible compared to the overall radiation exposure as a part of the treatment. The additional exposure to the staff due to induced activity from photon beams is small at an estimated level of about 1 to 2 mSv y. This is well below the allowed occupational exposure limits. Therefore, the potential hazard to staff from induced radioactivity in the use of high-energy x-rays is considered to be low, and no specific actions are considered necessary or mandatory. However, in the spirit of the "As Low as Reasonably Achievable (ALARA)" program, some reasonable steps are recommended that can be taken to reduce this small exposure to an even lower level. The dose reduction strategies suggested should be followed only if these actions are considered reasonable and practical in the individual clinics. Therapists working with proton beam and neutron beam units handle treatment devices that do become radioactive, and they should wear extremity monitors and make handling apertures and boluses their last task upon entering the room following treatment. Personnel doses from neutron-beam units can approach regulatory limits depending on the number of patients and beams, and strategies to reduce doses should be followed.

Immunomodulatory activity of a plant extract containing human papillomavirus 16-E7 protein in human monocyte-derived dendritic cells.

PubMed

Di Bonito, P; Grasso, F; Mangino, G; Massa, S; Illiano, E; Franconi, R; Fanales-Belasio, E; Falchi, M; Affabris, E; Giorgi, C

2009-01-01

This study reports the immunomodulatory activity on human monocyte derived dendritic cells (MDDCs) of a vaccine preparation shown to be effective against an HPV16-related tumour in an animal model. The vaccine is composed of extract from Nicotiana benthamiana leaves containing HPV16 E7 protein expressed by a potato virus X-derived vector (NbPVX-E7). The effect of the extract was evaluated on MDDC differentiation and maturation by monitoring the phenotypic expression of specific markers. The results show that NbPVX-E7 does not induce monocyte differentiation to dendritic cells, but does induce MDDC maturation. Plant extract does not influence MDDC-uptake of E7-FITC while it significantly improves the Ovalbumin-FITC uptake, considered as a model antigen. Importantly, NbPVX-E7-pulsed MDDCs/PBMCs are able to prime human blood-derived lymphocytes from healthy individuals to induce HPV16 E7-specific cytotoxic activity. This is a propaedeutic study for a possible use of E7-containing plant extract in human immunotherapy of HPV-related lesions.

Induction of Protease Release of the Resistant Diatom Chaetoceros didymus in Response to Lytic Enzymes from an Algicidal Bacterium

PubMed Central

Paul, Carsten; Pohnert, Georg

2013-01-01

Marine lytic bacteria can have a substantial effect on phytoplankton and are even capable to terminate blooms of microalgae. The bacterium Kordia algicida was reported to lyse cells of the diatom Skeletonema costatum and several other diatoms by a quorum sensing controlled excretion of proteases. However the diatom Chaetoceros didymus is fully resistant against the bacterial enzymes. We show that the growth curve of this diatom is essentially unaffected by addition of bacterial filtrates that are active against other diatoms. By monitoring proteases from the medium using zymography and fluorescence based activity assays we demonstrate that C. didymus responds to the presence of the lytic bacteria with the induced production of algal proteases. These proteases exhibit a substantially increased activity compared to the bacterial counterparts. The induction is also triggered by signals in the supernatant of a K. algicida culture. Size fractionation shows that only the >30 kD fraction of the bacterial exudates acts as an inducing cue. Implications for a potential induced defense of the diatom C. didymus are discussed. PMID:23469204

Troglitazone induces differentiation in Trypanosoma brucei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Denninger, Viola; Figarella, Katherine; Schoenfeld, Caroline

2007-05-15

Trypanosoma brucei, a protozoan parasite causing sleeping sickness, is transmitted by the tsetse fly and undergoes a complex lifecycle including several defined stages within the insect vector and its mammalian host. In the latter, differentiation from the long slender to the short stumpy form is induced by a yet unknown factor of trypanosomal origin. Here we describe that some thiazolidinediones are also able to induce differentiation. In higher eukaryotes, thiazolidinediones are involved in metabolism and differentiation processes mainly by binding to the intracellular receptor peroxisome proliferator activated receptor {gamma}. Our studies focus on the effects of troglitazone on bloodstream formmore » trypanosomes. Differentiation was monitored using mitochondrial markers (membrane potential, succinate dehydrogenase activity, inhibition of oxygen uptake by KCN, amount of cytochrome transcripts), morphological changes (Transmission EM and light microscopy), and transformation experiments (loss of the Variant Surface Glycoprotein coat and increase of dihydroliponamide dehydrogenase activity). To further investigate the mechanisms responsible for these changes, microarray analyses were performed, showing an upregulation of expression site associated gene 8 (ESAG8), a potential differentiation regulator.« less

Investigation of 3He-induced reactions on natural Ti for nuclear analytical and radionuclide production purposes

NASA Astrophysics Data System (ADS)

Ditrói, F.; Tárkányi, F.; Ali, M. A.; Andó, L.; Heselius, S.-J.; Shubin, Yu.; Youxiang, Zhuang; Mustafa, M. G.

2000-07-01

Excitation Russian Federation functions of 3He-induced nuclear reactions producing 43,44m,46,47,48Sc, 48V, 48,49,51Cr were measured up to 36 MeV bombarding energy by using the stacked-foil technique on different medium-energy accelerators. The results were compared with the data (cross-section, thick-target yield, activity-distribution functions, …) from the literature, model calculations and other measurements. Earlier measurements at higher energies up to 135 MeV are also plotted to complete the database for 3He-reactions on natural Ti. The new experimental and literature data were compared with the predictions of different model calculations for the 48V producing reactions. The selected experimental data sets were fitted using different methods to obtain recommended values. The measurements and compilation proved, that the 3He induced reactions on natural titanium, especially those leading to 48V and 48Cr are especially useful for monitoring, for activation analysis and for Thin Layer Activation (TLA) purposes. Production of 48V as a radiotracer is also recommended.

Emission spectral analysis of caspase-3 activation during artesunate (ART)-induced apoptosis of human lung adenocarcinoma cell

NASA Astrophysics Data System (ADS)

Pan, Wen-liang; Chen, Tong-sheng; Qu, Junle

2009-02-01

Artesunate (ART), a semi-synthetic derivative of the sesquiterpene artemisinin extracted from the Chinese herb Artemisia annua, exerts a broad spectrum of clinical activity against human cancers. Artemisinin-derivative combination chemotherapy is recommended by WHO since it acts rapidly and is well tolerated and particularly effective. In present investigation, we used CKK-8 assay to assess the inhibitory effects of ART on human lung adenocarcinoma (ASTC-a-1) cells. Apoptotic activity of ART in ASTC-a-1 cells was detected by means of nuclear staining with Hoechst33258. In order to monitor the activity of caspase-3 during ART-induced ASTC-a-1 cells apoptosis, the dynamical emission spectra of SCAT3, a FRET plasmid based on GFPs, were performed inside living cell expressed stably with SCAT3 after ART treatment. The results showed that (1) ART could inhibit ASTC-a-1 cells proliferation in a dose-dependent manner; (2) chromatin condensation was observed after ART treatment for 48 h; (3) the SCAT3 inside living cells were cleaved after ART treatment for 48 h, implying that caspase-3 was involved in the ART-induced apoptosis.

Brain Damage from Soman-Induced Seizures Is Greatly Exacerbated by Dimethyl sulfoxide (DMSO): Modest Neuroprotection by 2-Aminoethyl diphenylborinate (2- APB), a Transient Receptor Potential Channel Inhibitor and Inositol 1,4,5-triphosphate Receptor Antagonist

DTIC Science & Technology

2008-03-04

whereby the depletion of calcium from intracellular stores (e.g., via IP3 or ryanodine receptor activation ) signals the opening of calcium permeable TRP...system and allowed at least 30 min to acclimate. Baseline ECoG activity and behavior were monitored for at least 15 min. Following baseline recordings...used because the former does not cross the blood-brain-barrier and will not diminish seizure activity or interfere with central effects of the

Catalase-peroxidase activity has no influence on virulence in a murine model of tuberculosis.

PubMed

Cardona, Pere Joan; Gordillo, Sergi; Amat, Isabel; Díaz, Jorge; Lonca, Joan; Vilaplana, Cristina; Pallarés, Angeles; Llatjós, Roger; Ariza, Aurelio; Ausina, Vicenç

2003-01-01

The capacity to generate a chronic and persistent infection in the experimental murine model of tuberculosis induced aerogenically by a low-dose inoculum was determined in eight isoniazid-resistant clinical strains of Mycobacterium tuberculosis showing different catalase-peroxidase (C-P) activities. Determination of bacillary concentration in lung and spleen and the percentage of pulmonary parenchyma occupied by granulomas were monitored. Data showed no relation between the lack of C-P activity and the ability to develop a persistent infection, highlighting the potential of C-P negative strains to spread through the community.

Ultrasound enhanced thrombolysis: Clinical evidence

NASA Astrophysics Data System (ADS)

Alexandrov, Andrei V.

2005-04-01

Phase II CLOTBUST randomized clinical trial (Houston, Barcelona, Edmonton, Calgary) evaluated patients with acute ischemic stroke due to intracranial occlusion and treated with intravenous tissue plasminogen activator (TPA) within 3 h of symptom onset. Randomization: monitoring with pulsed wave 2 MHz transcranial Doppler (TCD) (Target) or placebo monitoring (Control). Safety: symptomatic bleeding to the brain (sICH). Primary end-point: complete recanalization on TCD or dramatic clinical recovery by the total NIHSS score <3, or improvement by >10 NIHSS points within 2 hours after TPA bolus. All projected 126 patients were randomized 1:1 to target (median NIHSS 16) or control (NIHSS 17). sICH: 4.8% Target, 4.8% Controls. Primary end-point was achieved by 31 (49%, Target) versus 19 (30%, Control), p<0.03. At 3 months, 22 (42% Target) and 14 (29% Control) patients achieved favorable outcomes. Continuous TCD monitoring of intracranial occlusion safely augments TPA-induced arterial recanalization, and 2 MHz diagnostic ultrasound has a positive biological activity that aids systemic thrombolytic therapy. For the first time in clinical medicine, the CLOTBUST trial provides the evidence that ultrasound enhances thrombolytic activity of a drug in humans thereby confirming intense multi-disciplinary experimental research conducted worldwide for the past 30 years.

Central administration of pansomatostatin agonist ODT8-SST prevents abdominal surgery-induced inhibition of circulating ghrelin, food intake and gastric emptying in rats

PubMed Central

STENGEL, A.; GOEBEL-STENGEL, M.; WANG, L.; LUCKEY, A.; HU, E.; RIVIER, J.; TACHÉ, Y.

2011-01-01

Background Activation of brain somatostatin receptors (sst1-5) with the stable pan-sst1-5 somatostatin agonist, ODT8-SST blocks acute stress and central corticotropin-releasing factor (CRF)-mediated activation of endocrine adrenal sympathetic responses. Brain CRF signaling is involved in delaying gastric emptying (GE) immediately post surgery. We investigated whether activation of brain sst signaling pathways modulates surgical stress-induced inhibition of gastric emptying and food intake. Methods Fasted rats were injected intracisternally (i.c.) with somatostatin agonists and underwent laparotomy and 1-min cecal palpation. GE of a non-nutrient solution and circulating acyl and desacyl ghrelin levels were assessed 50 min post surgery. Food intake was monitored for 24h. Key results The abdominal surgery-induced inhibition of GE (65%), food intake (73% at 2h) and plasma acyl ghrelin levels (67%) was completely prevented by ODT8-SST (1μg/rat, i.c.). The selective sst5 agonist, BIM-23052 prevented surgery-induced delayed GE, whereas selective sst1, sst2 or sst4 agonists had no effect. However, the selective sst2 agonist, S-346-011 (1μg/rat, i.c.) counteracted the abdominal surgery-induced inhibition of acyl ghrelin and food intake but not the delayed GE. The ghrelin receptor antagonist, [D-Lys3]-GHRP-6 (0.93 mg/kg, intraperitoneal, i.p.) blocked i.p. ghrelin-induced increased GE, while not influencing i.c. ODT8-SST-induced prevention of delayed GE and reduced food intake after surgery. Conclusions & Inferences ODT8-SST acts in the brain to prevent surgery-induced delayed GE likely via activating sst5. ODT8-SST and the sst2 agonist prevent the abdominal surgery-induced decrease in food intake and plasma acyl ghrelin indicating dissociation between brain somatostatin signaling involved in preventing surgery-induced suppression of GE and feeding response. PMID:21569179

Soil-plant interaction monitoring: Small scale example of an apple orchard in Trentino, North-Eastern Italy.

PubMed

Cassiani, Giorgio; Boaga, Jacopo; Rossi, Matteo; Putti, Mario; Fadda, Giuseppe; Majone, Bruno; Bellin, Alberto

2016-02-01

Accurate monitoring and modeling of soil-plant systems are a key unresolved issue that currently limits the development of a comprehensive view of the interactions between soil and atmosphere, with a number of practical consequences including the difficulties in predicting climatic change patterns. This paper presents a case study where time-lapse minimal-invasive 3D micro-electrical tomography (ERT) is used to monitor rhizosphere eco-hydrological processes in an apple orchard in the Trentino region, Northern Italy. In particular we aimed at gaining a better understanding of the soil-vegetation water exchanges in the shallow critical zone, as part of a coordinated effort towards predicting climate-induced changes on the hydrology of Mediterranean basins (EU FP7 CLIMB project). The adopted strategy relied upon the installation of a 3D electrical tomography apparatus consisting of four mini-boreholes carrying 12 electrodes each plus 24 mini-electrodes on the ground surface, arranged in order to image roughly a cubic meter of soil surrounding a single apple tree. The monitoring program was initially tested with repeated measurements over about one year. Subsequently, we performed three controlled irrigation tests under different conditions, in order to evaluate the water redistribution under variable root activities and climatic conditions. Laboratory calibration on soil samples allowed us to translate electrical resistivity variations into moisture content changes, supported also by in-situ TDR measurements. Richards equation modeling was used also to explain the monitoring evidence. The results clearly identified the effect of root water uptake and the corresponding subsoil region where active roots are present, but also marked the need to consider the effects of different water salinity in the water infiltration process. We also gained significant insight about the need to measure quantitatively the plant evapotranspiration in order to close the water balance and separate soil structure effects (primarily, hydraulic conductivity) from water dynamics induced by living plants. Copyright © 2015 Elsevier B.V. All rights reserved.

Monitoring population status of sea otters (Enhydra lutris) in Glacier Bay National Park and Preserve, Alaska: options and considerations

USGS Publications Warehouse

Esslinger, George G.; Esler, Daniel N.; Howlin, S.; Starcevich, L.A.

2015-06-25

After many decades of absence from southeast Alaska, sea otters (Enhydra lutris) are recolonizing parts of their former range, including Glacier Bay, Alaska. Sea otters are well known for structuring nearshore ecosystems and causing community-level changes such as increases in kelp abundance and changes in the size and number of other consumers. Monitoring population status of sea otters in Glacier Bay will help park researchers and managers understand and interpret sea otter-induced ecosystem changes relative to other sources of variation, including potential human-induced impacts such as ocean acidification, vessel disturbance, and oil spills. This report was prepared for the National Park Service (NPS), Southeast Alaska Inventory and Monitoring Network following a request for evaluation of options for monitoring sea otter population status in Glacier Bay National Park and Preserve. To meet this request, we provide a detailed consideration of the primary method of assessment of abundance and distribution, aerial surveys, including analyses of power to detect interannual trends and designs to reduce variation around annual abundance estimates. We also describe two alternate techniques for evaluating sea otter population status—(1) quantifying sea otter diets and energy intake rates, and (2) detecting change in ages at death. In addition, we provide a brief section on directed research to identify studies that would further our understanding of sea otter population dynamics and effects on the Glacier Bay ecosystem, and provide context for interpreting results of monitoring activities.

Potential of plant genetic systems for monitoring and screening mutagens

PubMed Central

Nilan, R. A.

1978-01-01

Plants have too long been ignored as useful screening and monitoring systems of environmental mutagens. However, there are about a dozen reliable, some even unique, plant genetic systems that can increase the scope and effectiveness of chemical and physical mutagen screening and monitoring procedures. Some of these should be included in the Tier II tests. Moreover, plants are the only systems now in use as monitors of genetic effects caused by polluted atmosphere and water and by pesticides. There are several major advantages of the plant test systems which relate to their reproductive nature, easy culture and growth habits that should be considered in mutagen screening and monitoring. In addition to these advantages, the major plant test systems exhibit numerous genetic and chromosome changes for determining the effects of mutagens. Some of these have not yet been detected in other nonmammalian and mammalian test systems, but probably occur in the human organism. Plants have played major roles in various aspects of mutagenesis research, primarily in mutagen screening (detection and verification of mutagenic activity), mutagen monitoring, and determining mutagen effects and mechanisms of mutagen action. They have played lesser roles in quantification of mutagenic activity and understanding the nature of induced mutations. Mutagen monitoring with plants, especially in situ on land or in water, will help determine potential genetic hazards of air and water pollutants and protect the genetic purity of crop plants and the purity of the food supply. The Tradescantia stamen-hair system is used in a mobile laboratory for determining the genetic effects of industrial and automobile pollution in a number of sites in the U.S.A. The fern is employed for monitoring genetic effects of water pollution in the Eastern states. The maize pollen system and certain weeds have monitored genetic effects of pesticides. Several other systems that have considerable value and should be developed and more widely used in mutagen monitoring and screening, especially for in situ monitoring, are discussed. Emphasis is placed on pollen systems in which changes in pollen structure, chemistry, and chromosomes can be scored for monitoring; and screening systems which can record low levels of genetic effects as well as provide information on the nature of induced mutations. The value of plant systems for monitoring and screening mutagens can be improved by: greater knowledge of plant cell processes at the molecular and ultrastructural levels; relating these processes to mutagen effects and plant cell responses; improving current systems for increased sensitivity, ease of detecting genetic and chromosome changes, recording of data (including automation), and for extending the range of genetic and chromosome end points; and designing and developing new systems with the aid of previous and current botanical and genetic knowledge. PMID:367768

Microbubble-Assisted Ultrasound-Induced Transient Phosphatidylserine Translocation.

PubMed

Escoffre, Jean-Michel; Derieppe, Marc; Lammertink, Bart; Bos, Clemens; Moonen, Chrit

2017-04-01

Microbubble-assisted ultrasound (sonopermeabilization) results in reversible permeabilization of the plasma membrane of cells. This method is increasingly used in vivo because of its potential to deliver therapeutic molecules with limited cell damage. Nevertheless, the effects of sonopermeabilization on the plasma membrane remain not fully understood. We investigated the influence of sonopermeabilization on the transverse mobility of phospholipids, especially on phosphatidylserine (PS) externalization. We performed studies using optical imaging with Annexin V and FM1-43 probes to monitor PS externalization of rat glioma C6 cells. Sonopermeabilization induced transient membrane permeabilization, which is positively correlated with reversible PS externalization. This membrane disorganization was temporary and not associated with loss of cell viability. Sonopermeabilization did not induce PS externalization via activation of the scramblase. We hypothesize that acoustically induced membrane pores may provide a new pathway for PS migration between both membrane leaflets. During the membrane-resealing phase, PS asymmetry may be re-established by amino-phospholipid flippase activity and/or endocytosis, along with exocytosis processes. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Effect of sympathetic activity on capsaicin-evoked pain, hyperalgesia, and vasodilatation.

PubMed

Baron, R; Wasner, G; Borgstedt, R; Hastedt, E; Schulte, H; Binder, A; Kopper, F; Rowbotham, M; Levine, J D; Fields, H L

1999-03-23

Painful nerve and tissue injuries can be exacerbated by activity in sympathetic neurons. The mechanisms of sympathetically maintained pain (SMP) are unclear. To determine the effect of cutaneous sympathetic activity on pain induced by primary afferent C-nociceptor sensitization with capsaicin in humans. In healthy volunteers capsaicin was applied topically (n = 12) or injected into the forearm skin (n = 10) to induce spontaneous pain, dynamic and punctate mechanical hyperalgesia, and antidromic (axon reflex) vasodilatation (flare). Intensity of pain and hyperalgesia, axon reflex vasodilatation (laser Doppler), and flare size and area of hyperalgesia (planimetry) were assessed. The local skin temperature at the application and measurement sites was kept constant at 35 degrees C. In each individual the analyses were performed during the presence of high and low sympathetic skin activity induced by whole-body cooling and warming with a thermal suit. By this method sympathetic vasoconstrictor activity is modulated in the widest range that can be achieved physiologically. The degree of vasoconstrictor discharge was monitored by measuring skin blood flow (laser Doppler) and temperature (infrared thermometry) at the index finger. The intensity and spatial distribution of capsaicin-evoked spontaneous pain and dynamic and punctate mechanical hyperalgesia were identical during the presence of high and low sympathetic discharge. Antidromic vasodilatation and flare size were significantly diminished when sympathetic vasoconstrictor neurons were excited. Cutaneous sympathetic vasoconstrictor activity does not influence spontaneous pain and mechanical hyperalgesia after capsaicin-induced C-nociceptor sensitization. When using physiologic stimulation of sympathetic activity, the capsaicin model is not useful for elucidating mechanisms of SMP. In neuropathic pain states with SMP, different mechanisms may be present.

Differences in magnesium and calcium effects on N-methyl-D-aspartate- and quisqualate-induced decreases in extracellular sodium concentration in rat hippocampal slices.

PubMed

Köhr, G; Heinemann, U

1988-01-01

Decreases in extracellular sodium concentration [( Na+]o) and associated slow negative field potentials (fp's) were monitored with double barreled sodium sensitive/reference microelectrodes in area CA1 of rat hippocampal slices during iontophoretic application of the glutamate receptor agonists N-methyl-D-aspartate (NMDA) and quisqualate (quis). The effects of lowering [Ca2+]o on these signals were compared to those of lowering [Mg2+]o. Both NMDA- and quis-induced decreases in [Na+]o of up to 60 mM and in the fp's of up to 8 mV. Decreasing [Mg2+]o enhanced NMDA-induced signals, whereas quis-induced signals were unaffected. Lowering [Ca2+]o also enhanced NMDA signals, although somewhat less than lowering [Mg2+]o. This effect was still present, even when voltage dependent Na+ currents were blocked by 10(-7) tetrodotoxin. Interestingly, quis-induced signals could be enhanced in a low Ca2+ medium as well, but only when high quis concentrations were used. The results suggest that, during the sorts of large decreases of [Ca2+]o observed during seizure activity, activation of NMDA receptors is facilitated.

Chronic sleep fragmentation during the sleep period induces hypothalamic endoplasmic reticulum stress and PTP1b-mediated leptin resistance in male mice.

PubMed

Hakim, Fahed; Wang, Yang; Carreras, Alba; Hirotsu, Camila; Zhang, Jing; Peris, Eduard; Gozal, David

2015-01-01

Sleep fragmentation (SF) is highly prevalent and may constitute an important contributing factor to excessive weight gain and the metabolic syndrome. Increased endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) leading to the attenuation of leptin receptor signaling in the hypothalamus leads to obesity and metabolic dysfunction. Mice were exposed to SF and sleep control (SC) for varying periods of time during which ingestive behaviors were monitored. UPR pathways and leptin receptor signaling were assessed in hypothalami. To further examine the mechanistic role of ER stress, changes in leptin receptor (ObR) signaling were also examined in wild-type mice treated with the ER chaperone tauroursodeoxycholic acid (TUDCA), as well as in CHOP-/+ transgenic mice. Fragmented sleep in male mice induced increased food intake starting day 3 and thereafter, which was preceded by increases in ER stress and activation of all three UPR pathways in the hypothalamus. Although ObR expression was unchanged, signal transducer and activator of transcription 3 (STAT3) phosphorylation was decreased, suggesting reduced ObR signaling. Unchanged suppressor of cytokine signaling-3 (SOCS3) expression and increases in protein-tyrosine phosphatase 1B (PTP1B) expression and activity emerged with SF, along with reduced p-STAT3 responses to exogenous leptin. SF-induced effects were reversed following TUDCA treatment and were absent in CHOP -/+ mice. SF induces hyperphagic behaviors and reduced leptin signaling in hypothalamus that are mediated by activation of ER stress, and ultimately lead to increased PTP1B activity. ER stress pathways are therefore potentially implicated in SF-induced weight gain and metabolic dysfunction, and may represent a viable therapeutic target. © 2014 Associated Professional Sleep Societies, LLC.

Establishment of a novel experimental protocol for drug-induced seizure liability screening based on a locomotor activity assay in zebrafish.

PubMed

Koseki, Naoteru; Deguchi, Jiro; Yamashita, Akihito; Miyawaki, Izuru; Funabashi, Hitoshi

2014-08-01

As drug-induced seizures have severe impact on drug development, evaluating seizure induction potential of candidate drugs at the early stages of drug discovery is important. A novel assay system using zebrafish has attracted interest as a high throughput toxicological in vivo assay system, and we tried to establish an experimental method for drug-induced seizure liability on the basis of locomotor activity in zebrafish. We monitored locomotor activity at high-speed movement (> 20 mm/sec) for 60 min immediately after exposure, and assessed seizure liability potential in some drugs using locomotor activity. However this experimental procedure was not sufficient for predicting seizures because the potential of several drugs with demonstrated seizure potential in mammals was not detected. We, therefore, added other parameters for locomotor activity such as extending exposure time or conducting flashlight stimulation (10 Hz) which is a known seizure induction stimulus, and these additional parameters improved seizure potential detection in some drugs. The validation study using the improved methodology was used to assess 52 commercially available drugs, and the prediction rate was approximately 70%. The experimental protocol established in this present study is considered useful for seizure potential screening during early stages of drug discovery.

Suppressive Effects of Pelargonidin on Endothelial Protein C Receptor Shedding via the Inhibition of TACE Activity and MAP Kinases.

PubMed

Kang, Hyejin; Lee, Taeho; Bae, Jong-Sup

2016-01-01

Beyond its role in the activation of protein C, the endothelial cell protein C receptor (EPCR) plays an important role in the cytoprotective pathway. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-[Formula: see text] converting enzyme (TACE). Pelargonidin is a well-known red pigment found in plants, and has been reported to have important biological activities that are potentially beneficial to human health. However, little is known about the effects of pelargonidin on EPCR shedding. We investigated this issue by monitoring the effects of pelargonidin on phorbol-12-myristate 13-acetate (PMA)-, tumor necrosis factor (TNF)-[Formula: see text]-, interleukin (IL)-1β-, and cecal ligation and puncture (CLP)-mediated EPCR shedding and by investigating the underlying mechanism of pelargonidin action. Data demonstrate that pelargonidin induced potent inhibition of PMA-, TNF-[Formula: see text]-, IL-1β-, and CLP-induced EPCR shedding by inhibiting the phosphorylation of mitogen-activated protein kinases (MAPKs) such as p38, janus kinase (JNK), and extracellular signal-regulated kinase (ERK) 1/2. Pelargonidin also inhibited the expression and activity of PMA-induced TACE in endothelial cells. These results demonstrate the potential of pelargonidin as an anti-EPCR shedding reagent against PMA- and CLP-mediated EPCR shedding.

Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

PubMed Central

May, Marcus; Gueler, Faikah; Barg-Hock, Hannelore; Heiringhoff, Karl-Heinz; Engeli, Stefan; Heusser, Karsten; Diedrich, André; Brandt, André; Strassburg, Christian P.; Tank, Jens; Sweep, Fred C. G. J.; Jordan, Jens

2011-01-01

Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups) after 30–40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. Trial Registration ClinicalTrials.gov NCT01237431 PMID:22016786

In vitro regulation of pericellular proteolysis in prostatic tumor cells treated with bombesin.

PubMed

Festuccia, C; Guerra, F; D'Ascenzo, S; Giunciuglio, D; Albini, A; Bologna, M

1998-01-30

Bombesin is a potent inducer of signal trasduction pathways involved in the proliferation and invasion of androgen-insensitive prostatic tumor cells. This study examines the bombesin-mediated modulation of pericellular proteolysis, monitoring cell capability to migrate and invade basement membranes, using a chemo-invasion assay and analyzing protease production. The results suggest that bombesin could modulate the invasive potential of prostatic cell lines regulating secretion and cell-surface uptake of uPA and MMP-9 activation. In fact, in PC3 and DU145 cells but not in LNCaP cells, urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) are induced by bombesin treatment. Bombesin also stimulates cell proliferation and this effect can be inhibited blocking uPA by antibodies and/or uPA inhibitor p-aminobenzamidine. Moreover, HMW-uPA induces cell proliferation in LNCaP cells, which do not produce uPA in the basal conditions, while PC3 and DU145 cell growth is supported by autocrine production of uPA. The increment of uPA activity on the external plasma membrane causes an increased pericellular plasmin activation. This effect is inhibited by antibodies against uPA and by p-aminobenzamidine. Similarly to EGF, bombesin stimulates secretion and activation of MMP-9 and TIMP-1 production. MMP-9 activation can be also obtained by HMW-uPA treatment, suggesting that plasma-membrane-bound uPA can start a proteolytic cascade involving MMP-9. Therefore, in in vitro assays, bombesin is able to modulate pericellular proteolysis and cell proliferation, differently distributing and activating proteolytic activities. This effect can be related to the "non-random" degradation of the extracellular matrix in which membrane uPA-uPAreceptor complexes could start bombesin-induced directional protein degradation during metastatic spread.

Pyruvate induces transient tumor hypoxia by enhancing mitochondrial oxygen consumption and potentiates the anti-tumor effect of a hypoxia-activated prodrug TH-302.

PubMed

Takakusagi, Yoichi; Matsumoto, Shingo; Saito, Keita; Matsuo, Masayuki; Kishimoto, Shun; Wojtkowiak, Jonathan W; DeGraff, William; Kesarwala, Aparna H; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Munasinghe, Jeeva P; Gillies, Robert J; Mitchell, James B; Hart, Charles P; Krishna, Murali C

2014-01-01

TH-302 is a hypoxia-activated prodrug (HAP) of bromo isophosphoramide mustard that is selectively activated within hypoxic regions in solid tumors. Our recent study showed that intravenously administered bolus pyruvate can transiently induce hypoxia in tumors. We investigated the mechanism underlying the induction of transient hypoxia and the combination use of pyruvate to potentiate the anti-tumor effect of TH-302. The hypoxia-dependent cytotoxicity of TH-302 was evaluated by a viability assay in murine SCCVII and human HT29 cells. Modulation in cellular oxygen consumption and in vivo tumor oxygenation by the pyruvate treatment was monitored by extracellular flux analysis and electron paramagnetic resonance (EPR) oxygen imaging, respectively. The enhancement of the anti-tumor effect of TH-302 by pyruvate treatment was evaluated by monitoring the growth suppression of the tumor xenografts inoculated subcutaneously in mice. TH-302 preferentially inhibited the growth of both SCCVII and HT29 cells under hypoxic conditions (0.1% O2), with minimal effect under aerobic conditions (21% O2). Basal oxygen consumption rates increased after the pyruvate treatment in SCCVII cells in a concentration-dependent manner, suggesting that pyruvate enhances the mitochondrial respiration to consume excess cellular oxygen. In vivo EPR oxygen imaging showed that the intravenous administration of pyruvate globally induced the transient hypoxia 30 min after the injection in SCCVII and HT29 tumors at the size of 500-1500 mm(3). Pretreatment of SCCVII tumor bearing mice with pyruvate 30 min prior to TH-302 administration, initiated with small tumors (∼ 550 mm(3)), significantly delayed tumor growth. Our in vitro and in vivo studies showed that pyruvate induces transient hypoxia by enhancing mitochondrial oxygen consumption in tumor cells. TH-302 therapy can be potentiated by pyruvate pretreatment if started at the appropriate tumor size and oxygen concentration.

Efficacy of intraoperative monitoring of transcranial electrical stimulation-induced motor evoked potentials and spontaneous electromyography activity to identify acute-versus delayed-onset C-5 nerve root palsy during cervical spine surgery: clinical article.

PubMed

Bhalodia, Vidya M; Schwartz, Daniel M; Sestokas, Anthony K; Bloomgarden, Gary; Arkins, Thomas; Tomak, Patrick; Gorelick, Judith; Wijesekera, Shirvinda; Beiner, John; Goodrich, Isaac

2013-10-01

Deltoid muscle weakness due to C-5 nerve root injury following cervical spine surgery is an uncommon but potentially debilitating complication. Symptoms can manifest upon emergence from anesthesia or days to weeks following surgery. There is conflicting evidence regarding the efficacy of spontaneous electromyography (spEMG) monitoring in detecting evolving C-5 nerve root compromise. By contrast, transcranial electrical stimulation-induced motor evoked potential (tceMEP) monitoring has been shown to be highly sensitive and specific in identifying impending C-5 injury. In this study the authors sought to 1) determine the frequency of immediate versus delayed-onset C-5 nerve root injury following cervical spine surgery, 2) identify risk factors associated with the development of C-5 palsies, and 3) determine whether tceMEP and spEMG neuromonitoring can help to identify acutely evolving C-5 injury as well as predict delayed-onset deltoid muscle paresis. The authors retrospectively reviewed the neuromonitoring and surgical records of all patients who had undergone cervical spine surgery involving the C-4 and/or C-5 level in the period from 2006 to 2008. Real-time tceMEP and spEMG monitoring from the deltoid muscle was performed as part of a multimodal neuromonitoring protocol during all surgeries. Charts were reviewed to identify patients who had experienced significant changes in tceMEPs and/or episodes of neurotonic spEMG activity during surgery, as well as those who had shown new-onset deltoid weakness either immediately upon emergence from the anesthesia or in a delayed fashion. Two hundred twenty-nine patients undergoing 235 cervical spine surgeries involving the C4-5 level served as the study cohort. The overall incidence of perioperative C-5 nerve root injury was 5.1%. The incidence was greatest (50%) in cases with dual corpectomies at the C-4 and C-5 spinal levels. All patients who emerged from anesthesia with deltoid weakness had significant and unresolved changes in tceMEPs during surgery, whereas only 1 had remarkable spEMG activity. Sensitivity and specificity of tceMEP monitoring for identifying acute-onset deltoid weakness were 100% and 99%, respectively. By contrast, sensitivity and specificity for spEMG were only 20% and 92%, respectively. Neither modality was effective in identifying patients who demonstrated delayed-onset deltoid weakness. The risk of new-onset deltoid muscle weakness following cervical spine surgery is greatest for patients undergoing 2-level corpectomies involving C-4 and C-5. Transcranial electrical stimulation-induced MEP monitoring is a highly sensitive and specific technique for detecting C-5 radiculopathy that manifests immediately upon waking from anesthesia. While the absence of sustained spEMG activity does not rule out nerve root irritation, the presence of excessive neurotonic discharges serves both to alert the surgeon of such potentially injurious events and to prompt neuromonitoring personnel about the need for additional tceMEP testing. Delayed-onset C-5 nerve root injury cannot be predicted by intraoperative neuromonitoring via either modality.

Design of the monitoring system at the Sant'Alessio induced riverbank filtration plant (Lucca, Italy)

NASA Astrophysics Data System (ADS)

Rossetto, Rudy; Barbagli, Alessio; Borsi, Iacopo; Mazzanti, Giorgio; Picciaia, Daniele; Vienken, Thomas; Bonari, Enrico

2015-04-01

In Managed Aquifer Recharge (MAR) schemes the monitoring system, for both water quality and quantity issues, plays a key role in assuring that a groundwater recharge plant is really managed. Considering induced Riverbank Filtration (RBF) schemes, while the effect of the augmented filtration consists in an improvement of the quality and quantity of the water infiltrating the aquifer, there is in turn the risk for groundwater contamination, as surface water bodies are highly susceptible to contamination. Within the framework of the MARSOL (2014) EU FPVII-ENV-2013 project, an experimental monitoring system has been designed and will be set in place at the Sant'Alessio RBF well field (Lucca, Italy) to demonstrate the sustainability and the benefits of managing induced RBF versus the unmanaged option. The RBF scheme in Sant'Alessio (Borsi et al. 2014) allows abstraction of an overall amount of about 0,5 m3/s groundwater providing drinking water for about 300000 people of the coastal Tuscany. Water is derived by ten vertical wells set along the Serchio River embankments inducing river water filtration into a high yield (10-2m2/s transmissivity) sand and gravel aquifer. Prior to the monitoring system design, a detailed site characterization has been completed taking advantage of previous and new investigations, the latter performed by means of MOSAIC on-site investigation platform (UFZ). A monitoring network has been set in place in the well field area using existing wells. There groundwater head and the main physico-chemical parameters (temperature, pH, dissolved oxygen, electrical conductivity and redox potential) are routinely monitored. Major geochemical compounds along with a large set of emerging pollutants are analysed (in cooperation with IWW Zentrum Wasser, Germany) both in surface-water and ground-water. The experimental monitoring system (including sensors in surface- and ground-water) has been designed focusing on managing abstraction efficiency and safety at one of the ten productive wells. The groundwater monitoring system consists of a set of six piezometer clusters drilled around a reference well along the main groundwater flowpaths. At each cluster, three piezometers (screened in the penultimate meter) are set at different depths to allow multilevel monitoring and sampling. At six selected piezometers, depending on ongoing hydrogeochemical investigations, six sensors for continuous monitoring of groundwater head, temperature and electrical conductivity will be set in operation. Within the Serchio River, two monitoring stations will be set in operation in order to monitor river head, water temperature and electrical conductivity upstream and downstream the experimental plot. A multi/parameter probe for the detection of selected analytes such nitrates, and selected organics to be defined will also be set in the Serchio River water. Each sensor will constitute a node of a Wireless Sensor Network (WSN). The WSN is based on several data loggers «client» connected via radio to one server point (Gateway), transmitting to a server via GSM-GPRS. This set up, while maintaining the high quality of data transmission, will allow to reduce installation and operational costs. The main characteristic of the conceived monitoring system is that sensors have been selected so to transmit data in an open format. The sensor network prototype will allow to get a substantial sensor cost reduction compared to available commercial solutions. The ultimate goal of this complex monitoring setting will be that of defining the minimum monitoring set up to guarantee efficiency and safety of groundwater withdrawals. Acknowledgements The authors wish to acknowledge GEAL spa for technical support and granting access to the well field. The activities described in this paper are co-financed within the framework of the EU FP7-ENV-2013-WATER-INNO-DEMO MARSOL (Grant Agreement n. 619120). References Borsi, I., Mazzanti, G., Barbagli, A., Rossetto, R., 2014. The riverbank filtration plant in S. Alessio (Lucca): monitoring and modeling activity within EU the FP7 MARSOL project. Acque Sotterranee - Italian Journal of Groundwater, Vol. 3, n. 3/137 MARSOL (2014). Demonstrating Managed Aquifer Recharge as a Solution to Water Scarcity and Drought www.marsol.eu [accessed 4 January 2015

Environmental stratification framework and water-quality monitoring design strategy for the Islamic Republic of Mauritania, Africa

USGS Publications Warehouse

Friedel, Michael J.

2008-01-01

Mauritania anticipates an increase in mining activities throughout the country and into the foreseeable future. Because mining-induced changes in the landscape are likely to affect their limited ground-water resources and sensitive aquatic ecosystems, a water-quality assessment program was designed for Mauritania that is based on a nationally consistent environmental stratification framework. The primary objectives of this program are to ensure that the environmental monitoring systems can quantify near real-time changes in surface-water chemistry at a local scale, and quantify intermediate- to long-term changes in groundwater and aquatic ecosystems over multiple scales.

Time-lapse monitoring of TLR2 ligand internalization with newly developed fluorescent probes.

PubMed

Arai, Yohei; Yokoyama, Kouhei; Kawahara, Yuki; Feng, Qi; Ohta, Ippei; Shimoyama, Atsushi; Inuki, Shinsuke; Fukase, Koichi; Kabayama, Kazuya; Fujimoto, Yukari

2018-05-23

As a mammalian toll-like receptor family member protein, TLR2 recognizes lipoproteins from bacteria and modulates the immune response by inducing the expression of various cytokines. We have developed fluorescence-labeled TLR2 ligands with either hydrophilic or hydrophobic fluorescence groups. The labeled ligands maintained the inflammatory IL-6 induction activity and enabled us to observe the internalization and colocalization of the TLR2 ligands using live-cell imaging. The time-lapse monitoring in the live-cell imaging of the fluorescence-labeled TLR2 ligand showed that TLR2/CD14 expression in the host cells enhanced the internalization of TLR2 ligand molecules.

An extract of Urtica dioica L. mitigates obesity induced insulin resistance in mice skeletal muscle via protein phosphatase 2A (PP2A).

PubMed

Obanda, Diana N; Ribnicky, David; Yu, Yongmei; Stephens, Jacqueline; Cefalu, William T

2016-02-26

The leaf extract of Urtica dioica L. (UT) has been reported to improve glucose homeostasis in vivo, but definitive studies on efficacy and mechanism of action are lacking. We investigated the effects of UT on obesity- induced insulin resistance in skeletal muscle. Male C57BL/6J mice were divided into three groups: low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with UT. Body weight, body composition, plasma glucose and plasma insulin were monitored. Skeletal muscle (gastrocnemius) was analyzed for insulin sensitivity, ceramide accumulation and the post translational modification and activity of protein phosphatase 2A (PP2A). PP2A is activated by ceramides and dephosphorylates Akt. C2C12 myotubes exposed to excess free fatty acids with or without UT were also evaluated for insulin signaling and modulation of PP2A. The HFD induced insulin resistance, increased fasting plasma glucose, enhanced ceramide accumulation and PP2A activity in skeletal muscle. Supplementation with UT improved plasma glucose homeostasis and enhanced skeletal muscle insulin sensitivity without affecting body weight and body composition. In myotubes, UT attenuated the ability of FFAs to induce insulin resistance and PP2A hyperactivity without affecting ceramide accumulation and PP2A expression. UT decreased PP2A activity through posttranslational modification that was accompanied by a reduction in Akt dephosphorylation.

Effects of pathogen reduction systems on platelet microRNAs, mRNAs, activation, and function

PubMed Central

Osman, Abdimajid; Hitzler, Walter E.; Meyer, Claudius U.; Landry, Patricia; Corduan, Aurélie; Laffont, Benoit; Boilard, Eric; Hellstern, Peter; Vamvakas, Eleftherios C.

2015-01-01

Pathogen reduction (PR) systems for platelets, based on chemically induced cross-linking and inactivation of nucleic acids, potentially prevent transfusion transmission of infectious agents, but can increase clinically significant bleeding in some clinical studies. Here, we documented the effects of PR systems on microRNA and mRNA levels of platelets stored in the blood bank, and assessed their impact on platelet activation and function. Unlike platelets subjected to gamma irradiation or stored in additive solution, platelets treated with Intercept (amotosalen + ultraviolet-A [UVA] light) exhibited significantly reduced levels of 6 of the 11 microRNAs, and 2 of the 3 anti-apoptotic mRNAs (Bcl-xl and Clusterin) that we monitored, compared with platelets stored in plasma. Mirasol (riboflavin + UVB light) treatment of platelets did not produce these effects. PR neither affected platelet microRNA synthesis or function nor induced cross-linking of microRNA-sized endogenous platelet RNA species. However, the reduction in the platelet microRNA levels induced by Intercept correlated with the platelet activation (p < 0.05) and an impaired platelet aggregation response to ADP (p < 0.05). These results suggest that Intercept treatment may induce platelet activation, resulting in the release of microRNAs and mRNAs from platelets. The clinical implications of this reduction in platelet nucleic acids secondary to Intercept remain to be established. PMID:24749844

Using cross correlations of turbulent flow-induced ambient vibrations to estimate the structural impulse response. Application to structural health monitoring.

PubMed

Sabra, Karim G; Winkel, Eric S; Bourgoyne, Dwayne A; Elbing, Brian R; Ceccio, Steve L; Perlin, Marc; Dowling, David R

2007-04-01

It has been demonstrated theoretically and experimentally that an estimate of the impulse response (or Green's function) between two receivers can be obtained from the cross correlation of diffuse wave fields at these two receivers in various environments and frequency ranges: ultrasonics, civil engineering, underwater acoustics, and seismology. This result provides a means for structural monitoring using ambient structure-borne noise only, without the use of active sources. This paper presents experimental results obtained from flow-induced random vibration data recorded by pairs of accelerometers mounted within a flat plate or hydrofoil in the test section of the U.S. Navy's William B. Morgan Large Cavitation Channel. The experiments were conducted at high Reynolds number (Re > 50 million) with the primary excitation source being turbulent boundary layer pressure fluctuations on the upper and lower surfaces of the plate or foil. Identical deterministic time signatures emerge from the noise cross-correlation function computed via robust and simple processing of noise measured on different days by a pair of passive sensors. These time signatures are used to determine and/or monitor the structural response of the test models from a few hundred to a few thousand Hertz.

Catalytic Activity and Proton Translocation of Reconstituted Respiratory Complex I Monitored by Surface-Enhanced Infrared Absorption Spectroscopy.

PubMed

Gutiérrez-Sanz, Oscar; Forbrig, Enrico; Batista, Ana P; Pereira, Manuela M; Salewski, Johannes; Mroginski, Maria A; Götz, Robert; De Lacey, Antonio L; Kozuch, Jacek; Zebger, Ingo

2018-05-22

Respiratory complex I (CpI) is a key player in the way organisms obtain energy, being an energy transducer, which couples nicotinamide adenine dinucleotide (NADH)/quinone oxidoreduction with proton translocation by a mechanism that remains elusive so far. In this work, we monitored the function of CpI in a biomimetic, supported lipid membrane system assembled on a 4-aminothiophenol (4-ATP) self-assembled monolayer by surface-enhanced infrared absorption spectroscopy. 4-ATP serves not only as a linker molecule to a nanostructured gold surface but also as pH sensor, as indicated by concomitant density functional theory calculations. In this way, we were able to monitor NADH/quinone oxidoreduction-induced transmembrane proton translocation via the protonation state of 4-ATP, depending on the net orientation of CpI molecules induced by two complementary approaches. An associated change of the amide I/amide II band intensity ratio indicates conformational modifications upon catalysis which may involve movements of transmembrane helices or other secondary structural elements, as suggested in the literature [ Di Luca , Proc. Natl. Acad. Sci. U.S.A. , 2017 , 114 , E6314 - E6321 ].

Inhibitory effects of Persicariae Rhizoma aqueous extracts on experimental periodontitis and alveolar bone loss in Sprague-Dawley rats

PubMed Central

Kang, Su Jin; Lee, Eun Kyung; Han, Chang Hyun; Lee, Bong Hyo; Lee, Young Joon; Ku, Sae Kwang

2016-01-01

Persicariae Rhizoma (PR) is the dried stem parts of Persicaria tinctoria H. Gross (Polygonaceae), and has been traditionally used as anti-inflammatory and detoxifying agent. In the present study, the effects of PR aqueous extracts on ligation-induced experimental periodontitis (EPD) and associated alveolar bone loss in rats were examined. Following the induction of EPD in rats, PR extracts were orally administered once a day for 10 days, and the changes and gains in body weight, alveolar bone loss and total aerobic bacterial counts of buccal gingiva were observed with histopathological analysis. In addition, anti-inflammatory effects were evaluated by monitoring myeloperoxidase (MPO) activities, and interleukin (IL)-1β and tumor necrosis factor (TNF)-α contents, and anti-oxidant effects were investigated by measuring inducible nitric oxide synthase (iNOS) activities and malondialdehyde (MDA) levels. Bacterial proliferation, periodontitis and associated alveolar bone loss induced by ligature placement were significantly and dose-dependently inhibited by the treatment with PR extracts. The inhibitory effects of 200 mg/kg PR were similar to those of 5 mg/kg indomethacin on ligation-induced periodontitis and associated alveolar bone losses in this study. The results suggest that PR effectively inhibits ligature placement-induced periodontitis and alveolar bone loss in rats via antibacterial, antioxidative and anti-inflammatory activities. PMID:27588077

Phenylethylamine induces an increase in cytosolic Ca2+ in yeast.

PubMed

Pinontoan, Reinhard; Krystofova, Svetlana; Kawano, Tomonori; Mori, Izumi C; Tsuji, Frederick I; Iida, Hidetoshi; Muto, Shoshi

2002-05-01

Beta-phenylethylamine (PEA) induced an increase in cytosolic free calcium ion concentration ([Ca2+]c) in Saccharomyces cerevisiae cells monitored with transgenic aequorin, a Ca2+-dependent photoprotein. The PEA-induced [Ca2+]c increase was dependent on the concentrations of PEA applied, and the Ca2+ mostly originated from an extracellular source. Preceding the Ca2+ influx, H2O2 was generated in the cells by the addition of PEA. Externally added H2O2 also induced a [Ca2+]c increase. These results suggest that PEA induces the [Ca2+]c increase via H2O2 generation. The PEA-induced [Ca2+]c increase occurred in the mid1 mutant with a slightly smaller peak than in the wild-type strain, indicating that Mid1, a stretch-activated nonselective cation channel, may not be mainly involved in the PEA-induced Ca2+ influx. When PEA was applied, the MATa mid1 mutant was rescued from alpha-factor-induced death in a Ca2+-limited medium, suggesting that the PEA-induced [Ca2+]c increase can reinforce calcium signaling in the mating pheromone response pathway.

Curcumin protects against collagen-induced arthritis via suppression of BAFF production.

PubMed

Huang, Gang; Xu, Zhizhen; Huang, Yan; Duan, Xiaojun; Gong, Wei; Zhang, Yan; Fan, Jishan; He, Fengtian

2013-04-01

The aim of the present study was to evaluate whether the anti-Rheumatoid arthritis (RA) effect of curcumin is associated with the regulation of B cell-activating factor belonging to the TNF family (BAFF) production. Collagen-induced arthritis (CIA) was induced in DBA/1 J mice by immunization with bovine type II collagen. To investigate the anti-arthritic effect of curcumin in the CIA model, mice were injected intraperitoneally with curcumin (50 mg/kg) on every other day either from day 1 or from day 28 after the first immunization. The clinical severity of arthritis was monitored. BAFF, interleukin-6 (IL-6) and interferon-γ (IFNγ) production in serum were measured. Furthermore, the effect of curcumin on IFNγ-induced BAFF expression and transcriptional activation in B lymphocytes was determined by qPCR, Western Blot, and luciferase assay. Finally, IFNγ related signal transducers and activators of transcription 1 (STAT1) signaling in B lymphocytes were studied using Western Blot. Curcumin dramatically attenuated the progression and severity of CIA in DBA/1 J mice, accompanied with decrease of BAFF production in serum and spleen cells as well as decrease of serum IFNγ and IL-6. Treatment of B lymphocytes with curcumin suppressed IFNγ-induced BAFF expression, STAT1 phosphorylation and nuclear translocation, suggesting that curcumin may repress IFNγ-induced BAFF expression via negatively interfering with STAT1 signaling. The results of the present study suggest that suppression of BAFF production may be a novel mechanism by which curcumin improves RA.

Sun-induced fluorescence - a new probe of photosynthesis: First maps from the imaging spectrometer HyPlant.

PubMed

Rascher, U; Alonso, L; Burkart, A; Cilia, C; Cogliati, S; Colombo, R; Damm, A; Drusch, M; Guanter, L; Hanus, J; Hyvärinen, T; Julitta, T; Jussila, J; Kataja, K; Kokkalis, P; Kraft, S; Kraska, T; Matveeva, M; Moreno, J; Muller, O; Panigada, C; Pikl, M; Pinto, F; Prey, L; Pude, R; Rossini, M; Schickling, A; Schurr, U; Schüttemeyer, D; Verrelst, J; Zemek, F

2015-12-01

Variations in photosynthesis still cause substantial uncertainties in predicting photosynthetic CO2 uptake rates and monitoring plant stress. Changes in actual photosynthesis that are not related to greenness of vegetation are difficult to measure by reflectance based optical remote sensing techniques. Several activities are underway to evaluate the sun-induced fluorescence signal on the ground and on a coarse spatial scale using space-borne imaging spectrometers. Intermediate-scale observations using airborne-based imaging spectroscopy, which are critical to bridge the existing gap between small-scale field studies and global observations, are still insufficient. Here we present the first validated maps of sun-induced fluorescence in that critical, intermediate spatial resolution, employing the novel airborne imaging spectrometer HyPlant. HyPlant has an unprecedented spectral resolution, which allows for the first time quantifying sun-induced fluorescence fluxes in physical units according to the Fraunhofer Line Depth Principle that exploits solar and atmospheric absorption bands. Maps of sun-induced fluorescence show a large spatial variability between different vegetation types, which complement classical remote sensing approaches. Different crop types largely differ in emitting fluorescence that additionally changes within the seasonal cycle and thus may be related to the seasonal activation and deactivation of the photosynthetic machinery. We argue that sun-induced fluorescence emission is related to two processes: (i) the total absorbed radiation by photosynthetically active chlorophyll; and (ii) the functional status of actual photosynthesis and vegetation stress. © 2015 John Wiley & Sons Ltd.

Post-error Brain Activity Correlates With Incidental Memory for Negative Words

PubMed Central

Senderecka, Magdalena; Ociepka, Michał; Matyjek, Magdalena; Kroczek, Bartłomiej

2018-01-01

The present study had three main objectives. First, we aimed to evaluate whether short-duration affective states induced by negative and positive words can lead to increased error-monitoring activity relative to a neutral task condition. Second, we intended to determine whether such an enhancement is limited to words of specific valence or is a general response to arousing material. Third, we wanted to assess whether post-error brain activity is associated with incidental memory for negative and/or positive words. Participants performed an emotional stop-signal task that required response inhibition to negative, positive or neutral nouns while EEG was recorded. Immediately after the completion of the task, they were instructed to recall as many of the presented words as they could in an unexpected free recall test. We observed significantly greater brain activity in the error-positivity (Pe) time window in both negative and positive trials. The error-related negativity amplitudes were comparable in both the neutral and emotional arousing trials, regardless of their valence. Regarding behavior, increased processing of emotional words was reflected in better incidental recall. Importantly, the memory performance for negative words was positively correlated with the Pe amplitude, particularly in the negative condition. The source localization analysis revealed that the subsequent memory recall for negative words was associated with widespread bilateral brain activity in the dorsal anterior cingulate cortex and in the medial frontal gyrus, which was registered in the Pe time window during negative trials. The present study has several important conclusions. First, it indicates that the emotional enhancement of error monitoring, as reflected by the Pe amplitude, may be induced by stimuli with symbolic, ontogenetically learned emotional significance. Second, it indicates that the emotion-related enhancement of the Pe occurs across both negative and positive conditions, thus it is preferentially driven by the arousal content of an affective stimuli. Third, our findings suggest that enhanced error monitoring and facilitated recall of negative words may both reflect responsivity to negative events. More speculatively, they can also indicate that post-error activity of the medial prefrontal cortex may selectively support encoding for negative stimuli and contribute to their privileged access to memory. PMID:29867408

Sweet Taste Receptor Expressed in Pancreatic β-Cells Activates the Calcium and Cyclic AMP Signaling Systems and Stimulates Insulin Secretion

PubMed Central

Nakagawa, Yuko; Nagasawa, Masahiro; Yamada, Satoko; Hara, Akemi; Mogami, Hideo; Nikolaev, Viacheslav O.; Lohse, Martin J.; Shigemura, Noriatsu; Ninomiya, Yuzo; Kojima, Itaru

2009-01-01

Background Sweet taste receptor is expressed in the taste buds and enteroendocrine cells acting as a sugar sensor. We investigated the expression and function of the sweet taste receptor in MIN6 cells and mouse islets. Methodology/Principal Findings The expression of the sweet taste receptor was determined by RT–PCR and immunohistochemistry. Changes in cytoplasmic Ca2+ ([Ca2+]c) and cAMP ([cAMP]c) were monitored in MIN6 cells using fura-2 and Epac1-camps. Activation of protein kinase C was monitored by measuring translocation of MARCKS-GFP. Insulin was measured by radioimmunoassay. mRNA for T1R2, T1R3, and gustducin was expressed in MIN6 cells. In these cells, artificial sweeteners such as sucralose, succharin, and acesulfame-K increased insulin secretion and augmented secretion induced by glucose. Sucralose increased biphasic increase in [Ca2+]c. The second sustained phase was blocked by removal of extracellular calcium and addition of nifedipine. An inhibitor of inositol(1, 4, 5)-trisphophate receptor, 2-aminoethoxydiphenyl borate, blocked both phases of [Ca2+]c response. The effect of sucralose on [Ca2+]c was inhibited by gurmarin, an inhibitor of the sweet taste receptor, but not affected by a Gq inhibitor. Sucralose also induced sustained elevation of [cAMP]c, which was only partially inhibited by removal of extracellular calcium and nifedipine. Finally, mouse islets expressed T1R2 and T1R3, and artificial sweeteners stimulated insulin secretion. Conclusions Sweet taste receptor is expressed in β-cells, and activation of this receptor induces insulin secretion by Ca2+ and cAMP-dependent mechanisms. PMID:19352508

Severe Hypoglycemia–Induced Lethal Cardiac Arrhythmias Are Mediated by Sympathoadrenal Activation

PubMed Central

Reno, Candace M.; Daphna-Iken, Dorit; Chen, Y. Stefanie; VanderWeele, Jennifer; Jethi, Krishan; Fisher, Simon J.

2013-01-01

For people with insulin-treated diabetes, severe hypoglycemia can be lethal, though potential mechanisms involved are poorly understood. To investigate how severe hypoglycemia can be fatal, hyperinsulinemic, severe hypoglycemic (10–15 mg/dL) clamps were performed in Sprague-Dawley rats with simultaneous electrocardiogram monitoring. With goals of reducing hypoglycemia-induced mortality, the hypotheses tested were that: 1) antecedent glycemic control impacts mortality associated with severe hypoglycemia; 2) with limitation of hypokalemia, potassium supplementation could limit hypoglycemia-associated deaths; 3) with prevention of central neuroglycopenia, brain glucose infusion could prevent hypoglycemia-associated arrhythmias and deaths; and 4) with limitation of sympathoadrenal activation, adrenergic blockers could prevent hypoglycemia-induced arrhythmic deaths. Severe hypoglycemia–induced mortality was noted to be worsened by diabetes, but recurrent antecedent hypoglycemia markedly improved the ability to survive an episode of severe hypoglycemia. Potassium supplementation tended to reduce mortality. Severe hypoglycemia caused numerous cardiac arrhythmias including premature ventricular contractions, tachycardia, and high-degree heart block. Intracerebroventricular glucose infusion reduced severe hypoglycemia–induced arrhythmias and overall mortality. β-Adrenergic blockade markedly reduced cardiac arrhythmias and completely abrogated deaths due to severe hypoglycemia. Under conditions studied, sudden deaths caused by insulin-induced severe hypoglycemia were mediated by lethal cardiac arrhythmias triggered by brain neuroglycopenia and the marked sympathoadrenal response. PMID:23835337

Quantitative monitoring of an activated sludge reactor using on-line UV-visible and near-infrared spectroscopy.

PubMed

Sarraguça, Mafalda C; Paulo, Ana; Alves, Madalena M; Dias, Ana M A; Lopes, João A; Ferreira, Eugénio C

2009-10-01

The performance of an activated sludge reactor can be significantly enhanced through use of continuous and real-time process-state monitoring, which avoids the need to sample for off-line analysis and to use chemicals. Despite the complexity associated with wastewater treatment systems, spectroscopic methods coupled with chemometric tools have been shown to be powerful tools for bioprocess monitoring and control. Once implemented and optimized, these methods are fast, nondestructive, user friendly, and most importantly, they can be implemented in situ, permitting rapid inference of the process state at any moment. In this work, UV-visible and NIR spectroscopy were used to monitor an activated sludge reactor using in situ immersion probes connected to the respective analyzers by optical fibers. During the monitoring period, disturbances to the biological system were induced to test the ability of each spectroscopic method to detect the changes in the system. Calibration models based on partial least squares (PLS) regression were developed for three key process parameters, namely chemical oxygen demand (COD), nitrate concentration (N-NO(3)(-)), and total suspended solids (TSS). For NIR, the best results were achieved for TSS, with a relative error of 14.1% and a correlation coefficient of 0.91. The UV-visible technique gave similar results for the three parameters: an error of approximately 25% and correlation coefficients of approximately 0.82 for COD and TSS and 0.87 for N-NO(3)(-) . The results obtained demonstrate that both techniques are suitable for consideration as alternative methods for monitoring and controlling wastewater treatment processes, presenting clear advantages when compared with the reference methods for wastewater treatment process qualification.

Differentiated NSC-34 cells as an in vitro cell model for VX.

PubMed

Kanjilal, Baishali; Keyser, Brian M; Andres, Devon K; Nealley, Eric; Benton, Betty; Melber, Ashley A; Andres, Jaclynn F; Letukas, Valerie A; Clark, Offie; Ray, Radharaman

2014-10-01

The US military has placed major emphasis on developing therapeutics against nerve agents (NA). Current efforts are hindered by the lack of effective in vitro cellular models to aid in the preliminary screening of potential candidate drugs/antidotes. The development of an in vitro cellular model to aid in discovering new NA therapeutics would be highly beneficial. In this regard, we have examined the response of a differentiated hybrid neuronal cell line, NSC-34, to the NA VX. VX-induced apoptosis of differentiated NSC-34 cells was measured by monitoring the changes in caspase-3 and caspase-9 activity post-exposure. Differentiated NSC-34 cells showed an increase in caspase-3 activity in a manner dependent on both time (17-23 h post-exposure) and dose (10-100 nM). The maximal increase in caspase-3 activity was found to be at 20-h post-exposure. Caspase-9 activity was also measured in response to VX and was found to be elevated at all concentrations (10-100 nM) tested. VX-induced cell death was also observed by utilizing annexin V/propidium iodide flow cytometry. Finally, VX-induced caspase-3 or -9 activities were reduced with the addition of pralidoxime (2-PAM), one of the current therapeutics used against NA toxicity, and dizocilpine (MK-801). Overall the data presented here show that differentiated NSC-34 cells are sensitive to VX-induced cell death and could be a viable in vitro cell model for screening NA candidate therapeutics.

Ethylenediaminetetraacetic acid induces antioxidant and anti-inflammatory activities in experimental liver fibrosis.

PubMed

González-Cuevas, J; Navarro-Partida, J; Marquez-Aguirre, A L; Bueno-Topete, M R; Beas-Zarate, C; Armendáriz-Borunda, J

2011-01-01

Experimental liver fibrosis induced by carbon tetrachloride (CCl(4)) is associated with oxidative stress, lipid peroxidation, and inflammation. This work was focused on elucidating the anti-inflammatory and antioxidant effects of ethylenediaminetetraacetic acid (EDTA) in this model of hepatotoxicity. Wistar male rats were treated with CCl(4) and EDTA (60, 120, or 240 mg/kg). Morphometric analyses were carried out in Masson's stained liver sections to determine fibrosis index. Coagulation tests prothrombin time (PT) and partial thromboplastin time (PTT) were also determined. Gene expression for transforming growth factor beta (TGF-beta1), alpha1(I) procollagen gene (alpha1 Col I), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and superoxide dismutase (SOD) was monitored by real-time PCR. Antioxidant effect of EDTA was measured by its effects on lipid peroxidation; biological activity of ceruloplasmin (Cp), SOD, and catalase (Cat) were analyzed by zymography assays. Animals with CCl(4)-hepatic injury that received EDTA showed a decrement in fibrosis (20%) and lipid peroxidation (22%). The mRNA expression for TNF-alpha (55%), TGF-beta1 (50%), IL-6 (52%), and alpha1 Col I (60%) was also decreased. This group of animals showed increased Cp (62%) and SOD (25%) biological activities. Coagulation blood tests, Cat activity, and gene expression for SOD were not modified by EDTA treatment. This study demonstrates that EDTA treatment induces the activity of antioxidant enzymes, decreases lipid peroxidation, hepatic inflammation, and fibrosis in experimental liver fibrosis induced by CCl(4).

Spontaneous motor activity during the development and maintenance of diet-induced obesity in the rat.

PubMed

Levin, B E

1991-09-01

More than 80% of most daily spontaneous activities (assessed in an Omnitech activity monitor) occurred during the last hour of light and 12 h of the dark phase in 8 chow-fed male Sprague-Dawley rats. Thirty additional rats were, therefore, monitored over this 13-h period to assess the relationship of activity to the development and maintenance of diet-induced obesity (DIO) on a diet high in energy, fat and sucrose (CM diet). Nine of 20 rats became obese after 3 months on the CM diet, with 71% greater weight gain than 10 chow-fed controls. Eleven of 20 rats were diet resistant (DR), gaining the same amount of weight as chow-fed rats. Neither initial activity levels nor initial body weights on chow (Period I) differed significantly across retrospectively identified groups. After 3 months on CM diet or chow (Period II), as well as after an additional 3 months after CM diet-fed rats returned to chow (Period III), there were significant inverse correlations (r = -.606 to -.370) between body weight at the time of testing and various measures of movement in the horizontal plane. There was no relationship to dietary content nor consistent correlations of body weight or diet group to vertical movements, an indirect measure of ingestive behavior. Patterns of time spent in the vertical position were significantly different for DIO vs. DR rats in Period III, however. Thus, differences in food intake and metabolic efficiency, rather than differences in nocturnal activity, are probably responsible for the greater weight gain in DIO-prone rats placed on CM diet.(ABSTRACT TRUNCATED AT 250 WORDS)

The Economics of Counterinsurgency in the Philippines

DTIC Science & Technology

2017-01-01

From- To) 24/01 /2017 Final Technical Report (UPDATED) June 2011 - June 2016 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER The Economics of...ORGANIZATION National Bureau of Economic Research, Inc. REPORT NUMBER 1050 Massachusetts Ave. Cambridge, MA 02138-5398 9. SPONSORING/MONITORING AGENCY NAME(S...14. ABSTRACT Economic activity can both induce and reduce political violence. We have shown that both insurgents and government respond to rising

Reconstructed Solar-Induced Fluorescence: A Machine Learning Vegetation Product Based on MODIS Surface Reflectance to Reproduce GOME-2 Solar-Induced Fluorescence

NASA Astrophysics Data System (ADS)

Gentine, P.; Alemohammad, S. H.

2018-04-01

Solar-induced fluorescence (SIF) observations from space have resulted in major advancements in estimating gross primary productivity (GPP). However, current SIF observations remain spatially coarse, infrequent, and noisy. Here we develop a machine learning approach using surface reflectances from Moderate Resolution Imaging Spectroradiometer (MODIS) channels to reproduce SIF normalized by clear sky surface irradiance from the Global Ozone Monitoring Experiment-2 (GOME-2). The resulting product is a proxy for ecosystem photosynthetically active radiation absorbed by chlorophyll (fAPARCh). Multiplying this new product with a MODIS estimate of photosynthetically active radiation provides a new MODIS-only reconstruction of SIF called Reconstructed SIF (RSIF). RSIF exhibits much higher seasonal and interannual correlation than the original SIF when compared with eddy covariance estimates of GPP and two reference global GPP products, especially in dry and cold regions. RSIF also reproduces intense productivity regions such as the U.S. Corn Belt contrary to typical vegetation indices and similarly to SIF.

Nitrosative stress mediated misfolded protein aggregation mitigated by Na-D-β-hydroxybutyrate intervention.

PubMed

Kabiraj, Parijat; Pal, Rituraj; Varela-Ramirez, Armando; Miranda, Manuel; Narayan, Mahesh

2012-09-28

Mitochondrial dysfunction, leading to elevated levels of reactive oxygen species, is associated with the pathogenesis of neurodegenerative disorders. Rotenone, a mitochondrial stressor induces caspase-9 and caspase-3 activation leading proteolytic cleavage of substrate nuclear poly(ADP-ribose) polymerase (PARP). PARP cleavage is directly related to apoptotic cell death. In this study, we have monitored the aggregation of green-fluorescent protein (GFP)-tagged synphilin-1, as a rotenone-induced Parkinsonia-onset biomarker. We report that the innate ketone body, Na-D-β-hydroxybutyrate (NaβHB) reduces markedly the incidence of synphilin-1 aggregation. Furthermore, our data reveal that the metabolic byproduct also prevents rotenone-induced caspase-activated apoptotic cell death in dopaminergic SH-SY5Y cells. Together, these results suggest that NaβHB is neuroprotective; it attenuates effects originating from mitochondrial insult and can serve as a scaffold for the design and development of sporadic neuropathies. Copyright © 2012 Elsevier Inc. All rights reserved.

Oxygen transfer rate identifies priming compounds in parsley cells.

PubMed

Schilling, Jana Viola; Schillheim, Britta; Mahr, Stefan; Reufer, Yannik; Sanjoyo, Sandi; Conrath, Uwe; Büchs, Jochen

2015-11-25

In modern agriculture, the call for an alternative crop protection strategy increases because of the desired reduction of fungicide and pesticide use and the continuously evolving resistance of pathogens and pests to agrochemicals. The direct activation of the plant immune system does not provide a promising plant protection measure because of high fitness costs. However, upon treatment with certain natural or synthetic compounds, plant cells can promote to a fitness cost-saving, primed state of enhanced defense. In the primed state, plants respond to biotic and abiotic stress with faster and stronger activation of defense, and this is often associated with immunity and abiotic stress tolerance. Until now, the identification of chemical compounds with priming-inducing activity (so-called plant activators) relied on tedious and invasive approaches, or required the late detection of secreted furanocoumarin phytoalexins in parsley cell cultures. Thus, simple, fast, straightforward, and noninvasive techniques for identifying priming-inducing compounds for plant protection are very welcome. This report demonstrates that a respiration activity-monitoring system (RAMOS) can identify compounds with defense priming-inducing activity in parsley cell suspension in culture. RAMOS relies on the quasi-continuous, noninvasive online determination of the oxygen transfer rate (OTR). Treatment of parsley culture cells with the known plant activator salicylic acid (SA), a natural plant defense signal, resulted in an OTR increase. Addition of the defense elicitor Pep13, a cell wall peptide of Phythophthora sojae, induced two distinctive OTR peaks that were higher in SA-primed cells than in unprimed cells upon Pep13 challenge. Both, the OTR increase after priming with SA and the Pep13 challenge were dose-dependent. Furthermore, there was a close correlation of a compound's activity to enhance the oxygen consumption in parsley cells and its capacity to prime Pep13-induced furanocoumarin secretion as evaluated by fluorescence spectroscopy. RAMOS noninvasively determines the OTR as a measure of the metabolic activity of plant cells. Chemical enhancement of oxygen consumption by salicylic derivatives in parsley cell suspension cultures correlates with the induction of the primed state of enhanced defense that enhances the quantity of Pep13-induced furanocoumarin phytoalexins. Treatment with the priming-active compounds methyl jasmonate and pyraclostrobin also resulted in an enhanced respiration activity. Thus, RAMOS is a novel technology for identifying priming-inducing compounds for agriculture.

Oxidative and Molecular Responses in Capsicum annuum L. after Hydrogen Peroxide, Salicylic Acid and Chitosan Foliar Applications

PubMed Central

Mejía-Teniente, Laura; de Dalia Durán-Flores, Flor; Chapa-Oliver, Angela María; Torres-Pacheco, Irineo; Cruz-Hernández, Andrés; González-Chavira, Mario M.; Ocampo-Velázquez, Rosalía V.; Guevara-González, Ramón G.

2013-01-01

Hydrogen peroxide (H2O2) is an important ROS molecule (Reactive oxygen species) that serves as a signal of oxidative stress and activation of signaling cascades as a result of the early response of the plant to biotic stress. This response can also be generated with the application of elicitors, stable molecules that induce the activation of transduction cascades and hormonal pathways, which trigger induced resistance to environmental stress. In this work, we evaluated the endogenous H2O2 production caused by salicylic acid (SA), chitosan (QN), and H2O2 elicitors in Capsicum annuum L. Hydrogen peroxide production after elicitation, catalase (CAT) and phenylalanine ammonia lyase (PAL) activities, as well as gene expression analysis of cat1, pal, and pathogenesis-related protein 1 (pr1) were determined. Our results displayed that 6.7 and 10 mM SA concentrations, and, 14 and 18 mM H2O2 concentrations, induced an endogenous H2O2 and gene expression. QN treatments induced the same responses in lesser proportion than the other two elicitors. Endogenous H2O2 production monitored during several days, showed results that could be an indicator for determining application opportunity uses in agriculture for maintaining plant alert systems against a stress. PMID:23676352

Intracellular ca2+ stores could participate to abscisic acid-induced depolarization and stomatal closure in Arabidopsis thaliana

PubMed Central

Meimoun, Patrice; Vidal, Guillaume; Bohrer, Anne-Sophie; Lehner, Arnaud; Tran, Daniel; Briand, Joël; Bouteau, François

2009-01-01

In Arabidopsis thaliana cell suspension,abscisic acid (aBa) induces changes in cytosolic calcium concentration ([Ca2+]cyt) which are the trigger for aBa-induced plasma membrane anion current activation, H+-aTPase inhibition, and subsequent plasma membrane depolarization. In the present study, we took advantage of this model to analyze the implication of intracellular Ca2+ stores in aBa signal transduction through electrophysiological current measurements, cytosolic Ca2+ activity measurements with the apoaequorin Ca2+ reporter protein and external pH measurement. Intracellular Ca2+ stores involvement was determined by using specific inhibitors of CICR channels: the cADP-ribose/ryanodine receptor (Br-cADPR and dantrolene) and of the inositol trisphosphate receptor (U73122). In addition experiments were performed on epidermal strips of A. thaliana leaves to monitor stomatal closure in response to ABA in presence of the same pharmacology. Our data provide evidence that ryanodine receptor and inositol trisphosphate receptor could be involved in ABA-induced (1) Ca2+ release in the cytosol, (2) anion channel activation and H+-ATPase inhibition leading to plasma membrane depolarization and (3) stomatal closure. Intracellular Ca2+ release could thus contribute to the control of early events in the ABA signal transduction pathway in A. thaliana. PMID:19847112

Wet, volatile, and dry biomarkers of exercise-induced muscle fatigue.

PubMed

Finsterer, Josef; Drory, Vivian E

2016-01-21

The physiological background of exercise-induced muscle fatigue(EIMUF) is only poorly understood. Thus, monitoring of EIMUF by a single or multiple biomarkers(BMs) is under debate. After a systematic literature review 91 papers were included. EIMUF is mainly due to depletion of substrates, increased oxidative stress, muscle membrane depolarisation following potassium depletion, muscle hyperthermia, muscle damage, impaired oxygen supply to the muscle, activation of an inflammatory response, or impaired calcium-handling. Dehydration, hyperammonemia, mitochondrial biogenesis, and genetic responses are also discussed. Since EIMUF is dependent on age, sex, degree of fatigue, type, intensity, and duration of exercise, energy supply during exercise, climate, training status (physical fitness), and health status, BMs currently available for monitoring EIMUF have limited reliability. Generally, wet, volatile, and dry BMs are differentiated. Among dry BMs of EIMUF the most promising include power output measures, electrophysiological measures, cardiologic measures, and questionnaires. Among wet BMs of EIMUF those most applicable include markers of ATP-metabolism, of oxidative stress, muscle damage, and inflammation. VO2-kinetics are used as a volatile BM. Though the physiology of EIMUF remains to be fully elucidated, some promising BMs have been recently introduced, which together with other BMs, could be useful in monitoring EIMUF. The combination of biomarkers seems to be more efficient than a single biomarker to monitor EIMUF. However, it is essential that efficacy, reliability, and applicability of each BM candidate is validated in appropriate studies.

Geophysical Observatory in Kamchatka region for monitoring of phenomena connected with seismic activity

NASA Astrophysics Data System (ADS)

Uyeda, S.; Nagao, T.; Hattori, K.; Hayakawa, M.; Miyaki, K.; Molchanov, O.; Gladychev, V.; Baransky, L.; Chtchekotov, A.; Fedorov, E.; Pokhotelov, O.; Andreevsky, S.; Rozhnoi, A.; Khabazin, Y.; Gorbatikov, A.; Gordeev, E.; Chebrov, V.; Sinitzin, V.; Lutikov, A.; Yunga, S.; Kosarev, G.; Surkov, V.; Belyaev, G.

Regular monitoring of some geophysical parameters in association with seismicity has been carried out since last year at the Japan-Russian Complex Geophysical Observatory in the Kamchatka region. This observatory was organized in connection with the ISTC project in Russia and was motivated by the results of the FRONTIER/RIKEN and FRONTIER/NASDA research projects in Japan. The main purpose of the observations is to investigate the electromagnetic and acoustic phenomena induced by the lithosphere processes (especially by seismic activity). The seismicity of the Kamchatka area is analyzed and a description of the observatory equipment is presented. At present, the activity of the observatory includes the seismic (frequency range ∆F = 0.5 - 40 Hz) and meteorological recordings, together with seismo-acoustic (∆F = 30 - 1000 Hz) and electromagnetic observations: three-component magnetic ULF variations ( ∆F = 0.003 - 30 Hz), three-component electric potential variations ( ∆F < 1.0 Hz), and VLF transmitter's signal perturbations ( ∆F ~ 10 - 40 kHz).

Intravital Imaging to Monitor Therapeutic Response in Moving Hypoxic Regions Resistant to PI3K Pathway Targeting in Pancreatic Cancer.

PubMed

Conway, James R W; Warren, Sean C; Herrmann, David; Murphy, Kendelle J; Cazet, Aurélie S; Vennin, Claire; Shearer, Robert F; Killen, Monica J; Magenau, Astrid; Mélénec, Pauline; Pinese, Mark; Nobis, Max; Zaratzian, Anaiis; Boulghourjian, Alice; Da Silva, Andrew M; Del Monte-Nieto, Gonzalo; Adam, Arne S A; Harvey, Richard P; Haigh, Jody J; Wang, Yingxiao; Croucher, David R; Sansom, Owen J; Pajic, Marina; Caldon, C Elizabeth; Morton, Jennifer P; Timpson, Paul

2018-06-12

Application of advanced intravital imaging facilitates dynamic monitoring of pathway activity upon therapeutic inhibition. Here, we assess resistance to therapeutic inhibition of the PI3K pathway within the hypoxic microenvironment of pancreatic ductal adenocarcinoma (PDAC) and identify a phenomenon whereby pronounced hypoxia-induced resistance is observed for three clinically relevant inhibitors. To address this clinical problem, we have mapped tumor hypoxia by both immunofluorescence and phosphorescence lifetime imaging of oxygen-sensitive nanoparticles and demonstrate that these hypoxic regions move transiently around the tumor. To overlay this microenvironmental information with drug response, we applied a FRET biosensor for Akt activity, which is a key effector of the PI3K pathway. Performing dual intravital imaging of drug response in different tumor compartments, we demonstrate an improved drug response to a combination therapy using the dual mTORC1/2 inhibitor AZD2014 with the hypoxia-activated pro-drug TH-302. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Nanomaterials Work at NASA-Johnson Space Center

NASA Technical Reports Server (NTRS)

Arepalli, Sivaram

2005-01-01

Nanomaterials activities at NASA-Johnson Space Center focus on single wall carbon nanotube production, characterization and their applications for aerospace. Nanotubes are produced by arc and laser methods and the growth process is monitored by in-situ diagnostics using time resolved passive emission and laser induced fluorescence of the active species. Parametric study of both these processes are conducted to monitor the effect of production parameters including temperature, buffer gas, flow rate, pressure, laser fluence and arc current. Characterization of the nanotube material is performed using the NASA-JSC protocol developed by combining analytical techniques of SEM, TEM, UV-VIS-NIR absorption, Raman, and TGA. Efforts at JSC over the past five years in composites have centered on structural polymernanotube systems. Recent activities broadened this focus to multifunctional materials, supercapacitors, fuel cells, regenerable CO2 absorbers, electromagnetic shielding, radiation dosimetry and thermal management systems of interest for human space flight. Preliminary tests indicate improvement of performance in most of these applications because of the large surface area as well as high conductivity exhibited by SWCNTs.

Live imaging of transforming growth factor-β activated kinase 1 activation in Lewis lung carcinoma 3LL cells implanted into syngeneic mice and treated with polyinosinic:polycytidylic acid.

PubMed

Takaoka, Saori; Kamioka, Yuji; Takakura, Kanako; Baba, Ai; Shime, Hiroaki; Seya, Tsukasa; Matsuda, Michiyuki

2016-05-01

Transforming growth factor-β activated kinase 1 (TAK1) has been shown to play a crucial role in cell death, differentiation, and inflammation. Here, we live-imaged robust TAK1 activation in Lewis lung carcinoma 3LL cells implanted into the s.c. tissue of syngeneic C57BL/6 mice and treated with polyinosinic:polycytidylic acid (PolyI:C). First, we developed and characterized a Förster resonance energy transfer-based biosensor for TAK1 activity. The TAK1 biosensor, named Eevee-TAK1, responded to stress-inducing reagents such as anisomycin, tumor necrosis factor-α, and interleukin1-β. The anisomycin-induced increase in Förster resonance energy transfer was abolished by the TAK1 inhibitor (5z)-7-oxozeaenol. Activity of TAK1 in 3LL cells was markedly increased by PolyI:C in the presence of macrophages. 3LL cells expressing Eevee-TAK1 were implanted into mice and observed through imaging window by two-photon excitation microscopy. During the growth of tumor, the 3LL cells at the periphery of the tumor showed higher TAK1 activity than the 3LL cells located at the center of the tumor, suggesting that cells at the periphery of the tumor mass were under stronger stress. Injection of PolyI:C, which is known to induce regression of the implanted tumors, induced marked and homogenous TAK1 activation within the tumor tissues. The effect of PolyI:C faded within 4 days. These observations suggest that Eevee-TAK1 is a versatile tool to monitor cellular stress in cancer tissues. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Distributed Attention Is Implemented through Theta-Rhythmic Gamma Modulation.

PubMed

Landau, Ayelet Nina; Schreyer, Helene Marianne; van Pelt, Stan; Fries, Pascal

2015-08-31

When subjects monitor a single location, visual target detection depends on the pre-target phase of an ∼8 Hz brain rhythm. When multiple locations are monitored, performance decrements suggest a division of the 8 Hz rhythm over the number of locations, indicating that different locations are sequentially sampled. Indeed, when subjects monitor two locations, performance benefits alternate at a 4 Hz rhythm. These performance alternations were revealed after a reset of attention to one location. Although resets are common and important events for attention, it is unknown whether, in the absence of resets, ongoing attention samples stimuli in alternation. Here, we examined whether spatially specific attentional sampling can be revealed by ongoing pre-target brain rhythms. Visually induced gamma-band activity plays a role in spatial attention. Therefore, we hypothesized that performance on two simultaneously monitored stimuli can be predicted by a 4 Hz modulation of gamma-band activity. Brain rhythms were assessed with magnetoencephalography (MEG) while subjects monitored bilateral grating stimuli for a unilateral target event. The corresponding contralateral gamma-band responses were subtracted from each other to isolate spatially selective, target-related fluctuations. The resulting lateralized gamma-band activity (LGA) showed opposite pre-target 4 Hz phases for detected versus missed targets. The 4 Hz phase of pre-target LGA accounted for a 14.5% modulation in performance. These findings suggest that spatial attention is a theta-rhythmic sampling process that is continuously ongoing, with each sampling cycle being implemented through gamma-band synchrony. Copyright © 2015 Elsevier Ltd. All rights reserved.

Levetiracetam versus phenytoin for seizure prophylaxis in severe traumatic brain injury

PubMed Central

Jones, Kristen E.; Puccio, Ava M.; Harshman, Kathy J.; Falcione, Bonnie; Benedict, Neal; Jankowitz, Brian T.; Stippler, Martina; Fischer, Michael; Sauber-Schatz, Erin K.; Fabio, Anthony; Darby, Joseph M.; Okonkwo, David O.

2013-01-01

Object Current standard of care for patients with severe traumatic brain injury (TBI) is prophylactic treatment with phenytoin for 7 days to decrease the risk of early posttraumatic seizures. Phenytoin alters drug metabolism, induces fever, and requires therapeutic-level monitoring. Alternatively, levetiracetam (Keppra) does not require serum monitoring or have significant pharmacokinetic interactions. In the current study, the authors compare the EEG findings in patients receiving phenytoin with those receiving levetiracetam monotherapy for seizure prophylaxis following severe TBI. Methods Data were prospectively collected in 32 cases in which patients received levetiracetam for the first 7 days after severe TBI and compared with data from a historical cohort of 41 cases in which patients received phenytoin monotherapy. Patients underwent 1-hour electroencephalographic (EEG) monitoring if they displayed persistent coma, decreased mental status, or clinical signs of seizures. The EEG results were grouped into normal and abnormal findings, with abnormal EEG findings further categorized as seizure activity or seizure tendency. Results Fifteen of 32 patients in the levetiracetam group warranted EEG monitoring. In 7 of these 15 cases the results were normal and in 8 abnormal; 1 patient had seizure activity, whereas 7 had seizure tendency. Twelve of 41 patients in the phenytoin group received EEG monitoring, with all results being normal. Patients treated with levetiracetam and phenytoin had equivalent incidence of seizure activity (p = 0.556). Patients receiving levetiracetam had a higher incidence of abnormal EEG findings (p = 0.003). Conclusions Levetiracetam is as effective as phenytoin in preventing early posttraumatic seizures but is associated with an increased seizure tendency on EEG analysis. PMID:18828701

Etomidate accurately localizes the epileptic area in patients with temporal lobe epilepsy.

PubMed

Pastor, Jesús; Wix, Rybel; Meilán, María Luisa; Martínez-Chacón, José Luís; de Dios, Eva; Domínguez-Gadea, Luis; Herrera-Peco, Iván; Sola, Rafael G

2010-04-01

A variety of drugs have been used to activate and identify the epileptogenic area in patients during presurgical evaluation. We have evaluated the safety and usefulness of etomidate in identifying the epileptic zone by measuring bioelectrical brain activity and cerebral blood flow (CBF). We studied 13 men and 9 women under presurgical evaluation for temporal lobe epilepsy. We applied etomidate (0.1 mg/kg) while patients were monitored by video-electroencephalography (VEEG) with foramen ovale electrodes. In a subset of 15 patients, we also measured CBF with single photon emission computed tomography (SPECT). (1) Etomidate induced seizures in 2 of 22 patients. (2) The main side-effects observed were myoclonus (14 of 20) and moderate pain (3 of 20). (3) No changes in capillary oxygen saturation, respiration, or heart rate were observed. (4) Irritative activity specifically increased in the temporal mesial and lateral areas. No spikes were observed in other areas, aside from those observed under baseline conditions. (5) Irritative activity induced by etomidate correctly lateralized the ictal onset zone in 19 of 20 patients. In addition, the two etomidate-induced seizures appeared in the same regions as spontaneous ones. (6) The kinetics of pharmacologically induced activity was higher in the region of the ictal-onset zone. (7) Etomidate increased the CBF in the basal ganglia and especially in the posterior hippocampus of the temporal mesial region contralateral to the ictal-onset zone. Etomidate activation is a safe, specific, and quick test that can be used to identify the epileptic region in patients evaluated as candidates for temporal lobe epilepsy surgery.

Lucidone suppresses dengue viral replication through the induction of heme oxygenase-1.

PubMed

Chen, Wei-Chun; Tseng, Chin-Kai; Lin, Chun-Kuang; Wang, Shen-Nien; Wang, Wen-Hung; Hsu, Shih-Hsien; Wu, Yu-Hsuan; Hung, Ling-Chien; Chen, Yen-Hsu; Lee, Jin-Ching

2018-01-01

Dengue virus (DENV) infection causes life-threatening diseases such as dengue hemorrhagic fever and dengue shock syndrome. Currently, there is no effective therapeutic agent or vaccine against DENV infection; hence, there is an urgent need to discover anti-DENV agents. The potential therapeutic efficacy of lucidone was first evaluated in vivo using a DENV-infected Institute of Cancer Research (ICR) suckling mouse model by monitoring body weight, clinical score, survival rate, and viral titer. We found that lucidone effectively protected mice from DENV infection by sustaining survival rate and reducing viral titers in DENV-infected ICR suckling mice. Then, the anti-DENV activity of lucidone was confirmed by western blotting and quantitative-reverse-transcription-polymerase chain reaction analysis, with an EC 50 value of 25 ± 3 μM. Lucidone significantly induced heme oxygenase-1 (HO-1) production against DENV replication by inhibiting DENV NS2B/3 protease activity to induce the DENV-suppressed antiviral interferon response. The inhibitory effect of lucidone on DENV replication was attenuated by silencing of HO-1 gene expression or blocking HO-1 activity. In addition, lucidone-stimulated nuclear factor erythroid 2-related factor 2 (Nrf2), which is involved in transactivation of HO-1 expression for its anti-DENV activity. Taken together, the mechanistic investigations revealed that lucidone exhibits significant anti-DENV activity in in vivo and in vitro by inducing Nrf2-mediated HO-1 expression, leading to blockage of viral protease activity to induce the anti-viral interferon (IFN) response. These results suggest that lucidone is a promising candidate for drug development.

Active and passive electrical and seismic time-lapse monitoring of earthen embankments

NASA Astrophysics Data System (ADS)

Rittgers, Justin Bradley

In this dissertation, I present research involving the application of active and passive geophysical data collection, data assimilation, and inverse modeling for the purpose of earthen embankment infrastructure assessment. Throughout the dissertation, I identify several data characteristics, and several challenges intrinsic to characterization and imaging of earthen embankments and anomalous seepage phenomena, from both a static and time-lapse geophysical monitoring perspective. I begin with the presentation of a field study conducted on a seeping earthen dam, involving static and independent inversions of active tomography data sets, and self-potential modeling of fluid flow within a confined aquifer. Additionally, I present results of active and passive time-lapse geophysical monitoring conducted during two meso-scale laboratory experiments involving the failure and self-healing of embankment filter materials via induced vertical cracking. Identified data signatures and trends, as well as 4D inversion results, are discussed as an underlying motivation for conducting subsequent research. Next, I present a new 4D acoustic emissions source localization algorithm that is applied to passive seismic monitoring data collected during a full-scale embankment failure test. Acoustic emissions localization results are then used to help spatially constrain 4D inversion of collocated self-potential monitoring data. I then turn to time-lapse joint inversion of active tomographic data sets applied to the characterization and monitoring of earthen embankments. Here, I develop a new technique for applying spatiotemporally varying structural joint inversion constraints. The new technique, referred to as Automatic Joint Constraints (AJC), is first demonstrated on a synthetic 2D joint model space, and is then applied to real geophysical monitoring data sets collected during a full-scale earthen embankment piping-failure test. Finally, I discuss some non-technical issues related to earthen embankment failures from a Science, Technology, Engineering, and Policy (STEP) perspective. Here, I discuss how the proclaimed scientific expertise and shifting of responsibility (Responsibilization) by governing entities tasked with operating and maintaining water storage and conveyance infrastructure throughout the United States tends to create barriers for 1) public voice and participation in relevant technical activities and outcomes, 2) meaningful discussions with the public and media during crisis communication, and 3) public perception of risk and the associated resilience of downhill communities.

An optically coupled system for quantitative monitoring of MRI-induced RF currents into long conductors.

PubMed

Zanchi, Marta G; Venook, Ross; Pauly, John M; Scott, Greig C

2010-01-01

The currents induced in long conductors such as guidewires by the radio-frequency (RF) field in magnetic resonance imaging (MRI) are responsible for potentially dangerous heating of surrounding media, such as tissue. This paper presents an optically coupled system with the potential to quantitatively measure the RF currents induced on these conductors. The system uses a self shielded toroid transducer and active circuitry to modulate a high speed light-emitting-diode transmitter. Plastic fiber guides the light to a photodiode receiver and transimpedance amplifier. System validation included a series of experiments with bare wires that compared wire tip heating by fluoroptic thermometers with the RF current sensor response. Validations were performed on a custom whole body 64 MHz birdcage test platform and on a 1.5 T MRI scanner. With this system, a variety of phenomena were demonstrated including cable trap current attenuation, lossy dielectric Q-spoiling and even transverse electromagnetic wave node patterns. This system should find applications in studies of MRI RF safety for interventional devices such as pacemaker leads, and guidewires. In particular, variations of this device could potentially act as a realtime safety monitor during MRI guided interventions.

Monitoring crater-wall collapse at active volcanoes: a study of the 12 January 2013 event at Stromboli

NASA Astrophysics Data System (ADS)

Calvari, Sonia; Intrieri, Emanuele; Di Traglia, Federico; Bonaccorso, Alessandro; Casagli, Nicola; Cristaldi, Antonio

2016-05-01

Crater-wall collapses are fairly frequent at active volcanoes and they are normally studied through the analysis of their deposits. In this paper, we present an analysis of the 12 January 2013 crater-wall collapse occurring at Stromboli volcano, investigated by means of a monitoring network comprising visible and infrared webcams and a Ground-Based Interferometric Synthetic Aperture Radar. The network revealed the triggering mechanisms of the collapse, which are comparable to the events that heralded the previous effusive eruptions in 1985, 2002, 2007 and 2014. The collapse occurred during a period of inflation of the summit cone and was preceded by increasing explosive activity and the enlargement of the crater. Weakness of the crater wall, increasing magmastatic pressure within the upper conduit induced by ascending magma and mechanical erosion caused by vent opening at the base of the crater wall and by lava fingering, are considered responsible for triggering the collapse on 12 January 2013 at Stromboli. We suggest that the combination of these factors might be a general mechanism to generate crater-wall collapse at active volcanoes.

Impact of Procyanidins from Different Berries on Caspase 8 Activation in Colon Cancer.

PubMed

Minker, Carole; Duban, Livine; Karas, Daniel; Järvinen, Päivi; Lobstein, Annelise; Muller, Christian D

2015-01-01

The aim of this work is to identify which proapoptotic pathway is induced in human colon cancer cell lines, in contact with proanthocyanidins extracted from various berries. Proanthocyanidins (Pcys) extracted from 11 berry species are monitored for proapoptotic activities on two related human colon cancer cell lines: SW480-TRAIL-sensitive and SW620-TRAIL-resistant. Apoptosis induction is monitored by cell surface phosphatidylserine (PS) detection. Lowbush blueberry extract triggers the strongest activity. When tested on the human monocytic cell line THP-1, blueberry Pcys are less effective for PS externalisation and DNA fragmentation is absent, highlighting a specificity of apoptosis induction in gut cells. In Pcys-treated gut cell lines, caspase 8 (apoptosis extrinsic pathway) but not caspase 9 (apoptosis intrinsic pathway) is activated after 3 hours through P38 phosphorylation (90 min), emphasizing the potency of lowbush blueberry Pcys to eradicate gut TRAIL-resistant cancer cells. We highlight here that berries Pcys, especially lowbush blueberry Pcys, are of putative interest for nutritional chemoprevention of colorectal cancer in view of their apoptosis induction in a human colorectal cancer cell lines.

Continuous Monitoring via Tethered Electroencephalography of Spontaneous Recurrent Seizures in Mice

PubMed Central

Bin, Na-Ryum; Song, Hongmei; Wu, Chiping; Lau, Marcus; Sugita, Shuzo; Eubanks, James H.; Zhang, Liang

2017-01-01

We describe here a simple, cost-effective apparatus for continuous tethered electroencephalographic (EEG) monitoring of spontaneous recurrent seizures in mice. We used a small, low torque slip ring as an EEG commutator, mounted the slip ring onto a standard mouse cage and connected rotary wires of the slip ring directly to animal's implanted headset. Modifications were made in the cage to allow for a convenient installation of the slip ring and accommodation of animal ambient activity. We tested the apparatus for hippocampal EEG recordings in adult C57 black mice. Spontaneous recurrent seizures were induced using extended hippocampal kindling (≥95 daily stimulation). Control animals underwent similar hippocampal electrode implantations but no stimulations were given. Combined EEG and webcam monitoring were performed for 24 h daily for 5–9 consecutive days. During the monitoring periods, the animals moved and accessed water and food freely and showed no apparent restriction in ambient cage activities. Ictal-like hippocampal EEG discharges and concurrent convulsive behaviors that are characteristics of spontaneous recurrent seizures were reliably recorded in a majority of the monitoring experiments in extendedly kindled but not in control animals. However, 1–2 rotary wires were disconnected from the implanted headset in some animals after continuous recordings for ≥5 days. The key features and main limitations of our recording apparatus are discussed. PMID:28959196

Hepatoprotective and antioxidant effects of Hygrophila auriculata (K. Schum) Heine Acanthaceae root extract.

PubMed

Shanmugasundaram, P; Venkataraman, S

2006-03-08

Hygrophila auriculata (K. Schum) Heine (syn. Asteracantha longifolia Nees, Acanthaceae) was widely used in the Indian systems of medicine for the treatment of various liver ailments. The hepatoprotective activity of the aqueous extract of the roots was studied on CCl(4)-induced liver toxicity in rats. The activity was assessed by monitoring the various liver function tests, viz. alanine transaminase, aspartate transaminase (AST), alkaline phosphatase (ALP), total protein and total bilirubin. Furthermore, hepatic tissues were subjected to histopathological studies. The root extract was also studied for its in vitro antioxidant activity using ferric thiocyanate (FTC) and thiobarbituric acid (TBA) methods. The extract exhibited significant hepatoprotective and antioxidant activities.

Carbon ions beam therapy monitoring with the INSIDE in-beam PET.

PubMed

Pennazio, Francesco; Battistoni, Giuseppe; Bisogni, Maria Giuseppina; Camarlinghi, Niccolò; Ferrari, Alfredo; Ferrero, Veronica; Fiorina, Elisa; Morrocchi, Matteo; Sala, Paola R; Sportelli, Giancarlo; Wheadon, Richard; Cerello, Piergiorgio

2018-06-06

In-vivo range monitoring techniques are necessary in order to fully take advantage of the high dose gradients deliverable in hadrontherapy treatments. Positron Emission Tomography (PET) scanners can be used to monitor beam-induced activation in tissues and hence measure the range. The INSIDE (Innovative Solutions for In-beam DosimEtry in Hadrontherapy) in-beam PET scanner, installed at the Italian National Center of Oncological Hadrontherapy (CNAO, Pavia, Italy) synchrotron facility, has already been successfully tested in-vivo during a proton therapy treatment. We discuss here the system performance evaluation with carbon ion beams, in view of future in-vivo tests. The work is focused on the analysis of activity images obtained with therapeutic treatments delivered to polymethyl methacrylate (PMMA) phantoms, as well as on the test of an innovative and robust Monte Carlo simulation technique for the production of reliable prior activity maps. Images are reconstructed using different integration intervals, so as to monitor the activity evolution during and after the treatment. Three procedures to compare activity images are presented, namely Pearson Correlation Coefficient, Beam's Eye View and Overall View. Images of repeated irradiations of the same treatments are compared to assess the integration time necessary to provide reproducible images. The range agreement between simulated and experimental images is also evaluated, so as to validate the simulation capability to provide sound prior information. The results indicate that at treatment end, or at most 20 s afterwards, the range measurement is reliable within 1-2 mm, when comparing both different experimental sessions and data with simulations. In conclusion, this work shows that the INSIDE in-beam PET scanner performance is promising towards its in-vivo test with carbon ions. © 2018 Institute of Physics and Engineering in Medicine.

Calreticulin mutants in mice induce an MPL-dependent thrombocytosis with frequent progression to myelofibrosis.

PubMed

Marty, Caroline; Pecquet, Christian; Nivarthi, Harini; El-Khoury, Mira; Chachoua, Ilyas; Tulliez, Micheline; Villeval, Jean-Luc; Raslova, Hana; Kralovics, Robert; Constantinescu, Stefan N; Plo, Isabelle; Vainchenker, William

2016-03-10

Frameshift mutations in the calreticulin (CALR) gene are seen in about 30% of essential thrombocythemia and myelofibrosis patients. To address the contribution of the CALR mutants to the pathogenesis of myeloproliferative neoplasms, we engrafted lethally irradiated recipient mice with bone marrow cells transduced with retroviruses expressing these mutants. In contrast to wild-type CALR, CALRdel52 (type I) and, to a lesser extent, CALRins5 (type II) induced thrombocytosis due to a megakaryocyte (MK) hyperplasia. Disease was transplantable into secondary recipients. After 6 months, CALRdel52-, in contrast to rare CALRins5-, transduced mice developed a myelofibrosis associated with a splenomegaly and a marked osteosclerosis. Monitoring of virus-transduced populations indicated that CALRdel52 leads to expansion at earlier stages of hematopoiesis than CALRins5. However, both mutants still specifically amplified the MK lineage and platelet production. Moreover, a mutant deleted of the entire exon 9 (CALRdelex9) did not induce a disease, suggesting that the oncogenic property of CALR mutants was related to the new C-terminus peptide. To understand how the CALR mutants target the MK lineage, we used a cell-line model and demonstrated that the CALR mutants, but not CALRdelex9, specifically activate the thrombopoietin (TPO) receptor (MPL) to induce constitutive activation of Janus kinase 2 and signal transducer and activator of transcription 5/3/1. We confirmed in c-mpl- and tpo-deficient mice that expression of Mpl, but not of Tpo, was essential for the CALR mutants to induce thrombocytosis in vivo, although Tpo contributes to disease penetrance. Thus, CALR mutants are sufficient to induce thrombocytosis through MPL activation. © 2016 by The American Society of Hematology.

IFN-γ, IL-2, IP-10, and MIG as Biomarkers of Exposure to Leishmania spp., and of Cure in Human Visceral Leishmaniasis.

PubMed

Ibarra-Meneses, Ana V; Ghosh, Prakash; Hossain, Faria; Chowdhury, Rajashree; Mondal, Dinesh; Alvar, Jorge; Moreno, Javier; Carrillo, Eugenia

2017-01-01

New biomarkers are needed for monitoring the effectiveness of treatment for visceral leishmaniasis (VL). They might also improve the detection of the asymptomatic population in Leishmania- endemic areas. This paper examines the IL-2, IFN-γ, IFN-γ-induced protein 10 (IP-10), and monokine-induced-by-IFN-γ (MIG) levels in whole blood-stimulated in vitro with soluble Leishmania antigen (SLA)-taken from asymptomatic individuals and patients treated for VL living in a post-outbreak ( Leishmania infantum ) area in Spain, and in an endemic ( Leishmania donovani ) area of Bangladesh. IP-10 was found to be an accurate global marker of asymptomatic subjects with positive cellular/humoral tests, while MIG was found to be a better marker of contact with L. donovani than IL-2 but no for those with L. infantum . Determining IP-10, MIG, and IFN-γ levels proved useful in monitoring the cellular immune response following treatment for active disease caused by L. infantum .

IFN-γ, IL-2, IP-10, and MIG as Biomarkers of Exposure to Leishmania spp., and of Cure in Human Visceral Leishmaniasis

PubMed Central

Ibarra-Meneses, Ana V.; Ghosh, Prakash; Hossain, Faria; Chowdhury, Rajashree; Mondal, Dinesh; Alvar, Jorge; Moreno, Javier; Carrillo, Eugenia

2017-01-01

New biomarkers are needed for monitoring the effectiveness of treatment for visceral leishmaniasis (VL). They might also improve the detection of the asymptomatic population in Leishmania-endemic areas. This paper examines the IL-2, IFN-γ, IFN-γ-induced protein 10 (IP-10), and monokine-induced-by-IFN-γ (MIG) levels in whole blood—stimulated in vitro with soluble Leishmania antigen (SLA)—taken from asymptomatic individuals and patients treated for VL living in a post-outbreak (Leishmania infantum) area in Spain, and in an endemic (Leishmania donovani) area of Bangladesh. IP-10 was found to be an accurate global marker of asymptomatic subjects with positive cellular/humoral tests, while MIG was found to be a better marker of contact with L. donovani than IL-2 but no for those with L. infantum. Determining IP-10, MIG, and IFN-γ levels proved useful in monitoring the cellular immune response following treatment for active disease caused by L. infantum. PMID:28620584

Monitoring Earth Surface Dynamics With Optical Imagery

NASA Astrophysics Data System (ADS)

Leprince, Sébastien; Berthier, Etienne; Ayoub, François; Delacourt, Christophe; Avouac, Jean-Philippe

2008-01-01

The increasing availability of high-quality optical satellite images should allow, in principle, continuous monitoring of Earth's surface changes due to geologic processes, climate change, or anthropic activity. For instance, sequential optical images have been used to measure displacements at Earth's surface due to coseismic ground deformation [e.g., Van Puymbroeck et al., 2000], ice flow [Scambos et al., 1992; Berthier et al., 2005], sand dune migration [Crippen, 1992], and landslides [Kääb, 2002; Delacourt et al., 2004]. Surface changes related to agriculture, deforestation, urbanization, and erosion-which do not involve ground displacement-might also be monitored, provided that the images can be registered with sufficient accuracy. Although the approach is simple in principle, its use is still limited, mainly because of geometric distortion of the images induced by the imaging system, biased correlation techniques, and implementation difficulties.

Possible involvements of glutamate and adrenergic receptors on acute toxicity of methylphenidate in isolated hippocampus and cerebral cortex of adult rats.

PubMed

Motaghinejad, Majid; Motevalian, Manijeh; Shabab, Behnaz

2017-04-01

Neurodegeneration induced by methylphenidate (MPH), as a central stimulant with unknown long-term consequences, in adult rats' brain and the possible mechanisms involved were studied. Rats were acutely treated with MPH in the presence and absence of some receptor antagonists such as ketamine, topiramate, yohimbine, and haloperidol. Motor activity and anxiety level in rats were monitored. Antioxidant and inflammatory parameters were also measured in isolated hippocampus and cerebral cortex. MPH-treated groups (10 and 20 mg/kg) demonstrated anxiety-like behavior and increased motor activity. MPH significantly increased lipid peroxidation, GSSG content, IL-1β and TNF-α levels in isolated tissues, and also significantly reduced GSH content, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in hippocampus and cerebral cortex. Pretreatment of animals by receptor antagonists caused inhibition of MPH-induced motor activity disturbances and anxiety-like behavior. Pretreatment of animals by ketamine, topiramate, and yohimbine inhibited the MPH-induced oxidative stress and inflammation; it significantly decreased lipid peroxidation, GSSG level, IL-1β and TNF-α levels and increased GSH content, SOD, GPx, and GR activities in hippocampus and cerebral cortex of acutely MPH-treated rats. Pretreatment with haloperidol did not cause any change in MPH-induced oxidative stress and inflammation. In conclusion, acute administration of high doses of MPH can cause oxidative and inflammatory changes in brain cells and induce neurodegeneration in hippocampus and cerebral cortex of adult rats and these changes might probably be mediated by glutamate (NMDA or AMPA) and/or α 2 -adrenergic receptors. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Changes in selected enzyme activities during growth of pure and mixed cultures of the white-rot decay fungus Trametes versicolor and the potential biocontrol fungus Trichoderma harzianum.

PubMed

Freitag, M; Morrell, J J

1992-04-01

Two filamentous fungi, the white-rot fungus Trametes versicolor and the soil fungus and potential biocontrol organism Trichoderma harzianum, have been grown in pure and mixed cultures on low-N (0.4 mM) and high-N (4 mM) defined synthetic media to determine the activities of selected wood-degrading enzymes such as cellobiase, cellulase, laccase, and peroxidases. Growth characteristics and enzyme activities were examined for potential correlations. Such correlations would allow the use of simple enzyme assays for measuring biomass development and would facilitate predictions about competitiveness of species in mixed fungal cultures. Our results show that while laccase and Poly Red-478 peroxidase activities indicate survival of the decay fungus, none of the monitored extracellular enzymes can serve as a quantitative indicator for biomass accumulation. As expected, the level of available nitrogen affected the production of the enzymes monitored: in low-N media, specific cellobiase, specific cellulase, and peroxidase activities were enhanced, while laccase activities were reduced. Most importantly, laccase activities of Trametes versicolor, and to a smaller extent, cellobiase activities of both fungi, were significantly induced in mixed cultures of Trametes versicolor and Trichoderma harzianum.

Antiplatelet, anticoagulant, and profibrinolytic activities of withaferin A.

PubMed

Ku, Sae-Kwang; Bae, Jong-Sup

2014-03-01

Withaferin A (WFA), an active compound from Withania somnifera, is widely researched for its anti-inflammatory, cardioactive and central nervous system effects. However, antiplatelet, anticoagulant, and profibrinolytic properties of WFA have not been studied. In this study, the anticoagulant activities of WFA were measured by monitoring activated partial thromboplastin-time (aPTT), prothrombin time (PT), fibrin polymerization, platelet aggregation, thrombus formation, and the activities of cell-based thrombin and activated factor X (FXa). The effects of WFA on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were also tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells (HUVECs). Our data showed that WFA inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation, FeCl3-induced thrombus formation, prolonged aPTT and PT significantly and inhibited the activities and production of thrombin and FXa. WFA prolonged in vivo and ex vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by WFA. Collectively, these results indicate that WFA possesses antithrombotic activities and suggest that the current study could provide bases for the development of new anticoagulant agents. Copyright © 2014 Elsevier Inc. All rights reserved.

Use of Small Fluorescent Molecules to Monitor Channel Activity

NASA Astrophysics Data System (ADS)

Jones, Sharon; Stringer, Sarah; Naik, Rajesh; Stone, Morley

2001-03-01

The Mechanosensitive channel of Large conductance (MscL) allows bacteria to rapidly adapt to changing environmental conditions such as osmolarity. The MscL channel opens in response to increases in membrane tension, which allows for the efflux of cytoplasmic constituents. Here we describe the cloning and expression of Salmonella typhimurium MscL (St-MscL). Using a fluorescence efflux assay, we demonstrate that efflux through the MscL channel during hypoosmotic shock can be monitored using endogenously produced fluorophores. In addition, we observe that thermal stimulation, i.e., heat shock, can also induce efflux through MscL. We present the first evidence of thermal activation of MscL efflux by heat shocking cells expressing the S. typhimurium protein variant. This finding has significant biosensor implications, especially for investigators exploring the use of channel proteins in biosensor applications. Thermal biosensors are relatively unexplored, but would have considerable commercial and military utility.

Monitoring protein-protein interactions using split synthetic renilla luciferase protein-fragment-assisted complementation.

PubMed

Paulmurugan, R; Gambhir, S S

2003-04-01

In this study we developed an inducible synthetic renilla luciferase protein-fragment-assisted complementation-based bioluminescence assay to quantitatively measure real time protein-protein interactions in mammalian cells. We identified suitable sites to generate fragments of N and C portions of the protein that yield significant recovered activity through complementation. We validate complementation-based activation of split synthetic renilla luciferase protein driven by the interaction of two strongly interacting proteins, MyoD and Id, in five different cell lines utilizing transient transfection studies. The expression level of the system was also modulated by tumor necrosis factor alpha through NFkappaB-promoter/enhancer elements used to drive expression of the N portion of synthetic renilla luciferase reporter gene. This new system should help in studying protein-protein interactions and when used with other split reporters (e.g., split firefly luciferase) should help to monitor different components of an intracellular network.

Monitoring Protein–Protein Interactions Using Split Synthetic Renilla Luciferase Protein-Fragment-Assisted Complementation

PubMed Central

Paulmurugan, R.; Gambhir, S. S.

2014-01-01

In this study we developed an inducible synthetic renilla luciferase protein-fragment-assisted complementation-based bioluminescence assay to quantitatively measure real time protein–protein interactions in mammalian cells. We identified suitable sites to generate fragments of N and C portions of the protein that yield significant recovered activity through complementation. We validate complementation-based activation of split synthetic renilla luciferase protein driven by the interaction of two strongly interacting proteins, MyoD and Id, in five different cell lines utilizing transient transfection studies. The expression level of the system was also modulated by tumor necrosis factor α through NFκB-promoter/enhancer elements used to drive expression of the N portion of synthetic renilla luciferase reporter gene. This new system should help in studying protein–protein interactions and when used with other split reporters (e.g., split firefly luciferase) should help to monitor different components of an intracellular network. PMID:12705589

A review of the 2005 Kashmir earthquake-induced landslides; from a remote sensing prospective

NASA Astrophysics Data System (ADS)

Shafique, Muhammad; van der Meijde, Mark; Khan, M. Asif

2016-03-01

The 8th October 2005 Kashmir earthquake, in northern Pakistan has triggered thousands of landslides, which was the second major factor in the destruction of the build-up environment, after earthquake-induced ground shaking. Subsequent to the earthquake, several researchers from home and abroad applied a variety of remote sensing techniques, supported with field observations, to develop inventories of the earthquake-triggered landslides, analyzed their spatial distribution and subsequently developed landslide-susceptibility maps. Earthquake causative fault rupture, geology, anthropogenic activities and remote sensing derived topographic attributes were observed to have major influence on the spatial distribution of landslides. These were subsequently used to develop a landslide susceptibility map, thereby demarcating the areas prone to landsliding. Temporal studies monitoring the earthquake-induced landslides shows that the earthquake-induced landslides are stabilized, contrary to earlier belief, directly after the earthquake. The biggest landslide induced dam, as a result of the massive Hattian Bala landslide, is still posing a threat to the surrounding communities. It is observed that remote sensing data is effectively and efficiently used to assess the landslides triggered by the Kashmir earthquake, however, there is still a need of more research to understand the mechanism of intensity and distribution of landslides; and their continuous monitoring using remote sensing data at a regional scale. This paper, provides an overview of remote sensing and GIS applications, for the Kashmir-earthquake triggered landslides, derived outputs and discusses the lessons learnt, advantages, limitations and recommendations for future research.

Biglycan, a danger signal that activates the NLRP3 inflammasome via toll-like and P2X receptors.

PubMed

Babelova, Andrea; Moreth, Kristin; Tsalastra-Greul, Wasiliki; Zeng-Brouwers, Jinyang; Eickelberg, Oliver; Young, Marian F; Bruckner, Peter; Pfeilschifter, Josef; Schaefer, Roland M; Gröne, Hermann-Josef; Schaefer, Liliana

2009-09-04

The role of endogenous inducers of inflammation is poorly understood. To produce the proinflammatory master cytokine interleukin (IL)-1beta, macrophages need double stimulation with ligands to both Toll-like receptors (TLRs) for IL-1beta gene transcription and nucleotide-binding oligomerization domain-like receptors for activation of the inflammasome. It is particularly intriguing to define how this complex regulation is mediated in the absence of an infectious trigger. Biglycan, a ubiquitous leucine-rich repeat proteoglycan of the extracellular matrix, interacts with TLR2/4 on macrophages. The objective of this study was to define the role of biglycan in the synthesis and activation of IL-1beta. Here we show that in macrophages, soluble biglycan induces the NLRP3/ASC inflammasome, activating caspase-1 and releasing mature IL-1beta without the need for additional costimulatory factors. This is brought about by the interaction of biglycan with TLR2/4 and purinergic P2X(4)/P2X(7) receptors, which induces receptor cooperativity. Furthermore, reactive oxygen species formation is involved in biglycan-mediated activation of the inflammasome. By signaling through TLR2/4, biglycan stimulates the expression of NLRP3 and pro-IL-1beta mRNA. Both in a model of non-infectious inflammatory renal injury (unilateral ureteral obstruction) and in lipopolysaccharide-induced sepsis, biglycan-deficient mice displayed lower levels of active caspase-1 and mature IL-1beta in the kidney, lung, and circulation. Our results provide evidence for direct activation of the NLRP3 inflammasome by biglycan and describe a fundamental paradigm of how tissue stress or injury is monitored by innate immune receptors detecting the release of the extracellular matrix components and turning such a signal into a robust inflammatory response.

Active secretion and protective effect of salivary nitrate against stress in human volunteers and rats

PubMed Central

Jin, Luyuan; Qin, Lizheng; Xia, Dengsheng; Liu, Xibao; Fan, Zhipeng; Zhang, Chunmei; Gu, Liankun; He, Junqi; Ambudkar, Indu S.; Deng, Dajun; Wang, Songlin

2014-01-01

Up to 25% of the circulating nitrate in blood is actively taken up, concentrated, and secreted into saliva by the salivary glands. Salivary nitrate can be reduced to nitrite by the commensal bacteria in the oral cavity or stomach and then further converted to nitric oxide (NO) in vivo, which may play a role in gastric protection. However, whether salivary nitrate is actively secreted in human beings has not yet been determined. This study was designed to determine whether salivary nitrate is actively secreted in human beings as an acute stress response and what role salivary nitrate plays in stress-induced gastric injury. To observe salivary nitrate function under stress conditions, alteration of salivary nitrate and nitrite was analyzed among 22 healthy volunteers before and after a strong stress activity, jumping down from a platform at the height of 68m. A series of stress indexes was analyzed to monitor the stress situation. We found that both the concentration and the total amount of nitrate in mixed saliva were significantly increased in the human volunteers immediately after the jump, with an additional increase 1 h later (p < 0.01). Saliva nitrite reached a maximum immediately after the jump and was maintained 1 h later. To study the biological functions of salivary nitrate and nitrite in stress protection, we further carried out a water-immersion-restraint stress (WIRS) assay in male adult rats with bilateral parotid and submandibular duct ligature (BPSDL). Intragastric nitrate, nitrite, and NO; gastric mucosal blood flow; and gastric ulcer index (UI) were monitored and nitrate was administrated in drinking water to compensate for nitrate secretion in BPSDL animals. Significantly decreased levels of intragastric nitrate, nitrite, and NO and gastricmucosal blood flow were measured in BPSDL rats during the WIRS assay compared to sham control rats (p < 0.05). Recovery was observed in the BPSDL rats upon nitrate administration. The WIRS-induced UI was significantly higher in the BPSDL animals compared to controls, and nitrate administration rescued the WIRS-induced gastric injury in BPSDL rats. In conclusion, this study suggests that stress promotes salivary nitrate secretion and nitrite formation, which may play important roles in gastric protection against stress-induced injury via the nitrate-dependent NO pathway. PMID:23277147

The exploitation of inflammation in photodynamic therapy of pleural cancer (Conference Presentation)

NASA Astrophysics Data System (ADS)

Davis, Richard W.; Miller, Joann; Houser, Cassandra L.; Klampatsa, Astero; Jenkins, Tim; Cengel, Keith A.; Albelda, Steven M.; Busch, Theresa M.

2017-02-01

The onset of inflammation is a well-known physiology in tumors treated with photodynamic therapy (PDT). After PDT, the release of danger signals causes an influx of neutrophils, activation of dendritic cells, and an eventual initiation of the adaptive immune response. However, inflammation also lies at a crucial fulcrum for treatment outcome, as it can stimulate the expression of resistance factors. Therefore, effective treatment with PDT requires an understanding of the holistic contribution of inflammation. Within, we outline two means of studying tumor inflammation in the setting of PDT. Experiments are conducted in murine models of mesothelioma, including those that incorporate surgery prior to PDT or pleural propagation of the disease. First, we use a chemiluminescent agent, luminol, to detect the influx of neutrophils by in vivo molecular imaging. This longitudinal approach allows for the repeated non-invasive monitoring of PDT-induced neutrophil influx. Data clearly identify protocol-specific differences in tumor-associated neutrophil activity. Second, we describe the application of cone-beam CT to detect the fibrosis associated with murine orthotropic mesothelioma models. This approach incorporates novel methods in image segmentation to accurately identify diffuse disease in the thoracic cavity. These studies lay the foundation for future research to correlate long-term response with local PDT-induced inflammation. Such methods in monitoring of inflammation or tumor burden will enable characterization of the consequences of combinatorial therapy (e.g., intraoperative PDT). Resulting data will guide the selection of pharmacological agents or molecular imaging techniques that respectively exploit inflammation for therapeutic or monitoring purposes.

Muscle Sympathetic Nerve Activity During Intense Lower Body Negative Pressure to Presyncope in Humans

DTIC Science & Technology

2009-08-24

frequency rhythms. Arterial pressure oscillations increase with reductions in central blood volume induced by haemorrhage (Guyton & Harris, 1951), head...a finger cuff to record beat-by-beat finger arterial pressure (Finometer Blood Pressure Monitor, TNO-TPD Biomedical Instrumentation, Amsterdam, The...experienced reductions in arterial pressure at presyncope. The lowest blood pressures recorded for each subject are shown in the upper right of each

Antiinflammatory effects of Cordia myxa fruit on experimentally induced colitis in rats.

PubMed

Al-Awadi, F M; Srikumar, T S; Anim, J T; Khan, I

2001-05-01

Products of certain species of Cordia are reported to have antiinflammatory properties. In the present study we examined the effects of Cordia myxa fruit on experimentally induced colitis in rats. Colitis was induced by intrarectal administration of 4% acetic acid. Colitic, normal, and corresponding control animals were included. Body weight was recorded daily. All the animals were sacrificed 4 days after the fruit treatment. Colitis was monitored histologically and by activity of myeloperoxidase. Glutathione peroxidase, superoxide dismutase, as well as total antioxidant status and concentrations of zinc, copper, manganese, selenium, and iron were assayed in plasma, liver, and colon using standard methods. Histology of the colon of colitic rats showed acute colitis that was confirmed by a significant increase in the myeloperoxidase activity. Colitis was associated with significant decreases in the tissue activities of glutathione peroxidase and superoxide dismutase and lower concentrations of trace elements. Histologic examination and myeloperoxidase activity showed that the fruit treatment reversed the above findings in the inflamed colon, and in liver and plasma of colitic rats. The present results suggest that the observed antiinflammatory effect of the Cordia myxa may be attributed partly to its antioxidant property and to restoration of the levels of trace elements in the inflamed colon, liver, and plasma.

Quercetin Improves Neurobehavioral Performance Through Restoration of Brain Antioxidant Status and Acetylcholinesterase Activity in Manganese-Treated Rats.

PubMed

Adedara, Isaac A; Ego, Valerie C; Subair, Temitayo I; Oyediran, Oluwasetemi; Farombi, Ebenezer O

2017-04-01

The present study investigated the neuroprotective mechanism of quercetin by assessing the biochemical and behavioral characteristics in rats sub-chronically treated with manganese alone at 15 mg/kg body weight or orally co-treated with quercetin at 10 and 20 mg/kg body weight for 45 consecutive days. Locomotor behavior was monitored using video-tracking software during a 10-min trial in a novel environment whereas the brain regions namely the hypothalamus, cerebrum and cerebellum of the rats were processed for biochemical analyses. Results indicated that co-treatment with quercetin significantly (p < 0.05) prevented manganese-induced locomotor and motor deficits specifically the decrease in total distance travelled, total body rotation, maximum speed, absolute turn angle as well as the increase in time of immobility and grooming. The improvement in the neurobehavioral performance of manganese-treated rats following quercetin co-treatment was confirmed by track and occupancy plot analyses. Moreover, quercetin assuaged manganese-induced decrease in antioxidant enzymes activities and the increase in acetylcholinesterase activity, hydrogen peroxide generation and lipid peroxidation levels in the hypothalamus, cerebrum and cerebellum of the rats. Taken together, quercetin mechanisms of ameliorating manganese-induced neurotoxicity is associated with restoration of acetylcholinesterase activity, augmentation of redox status and inhibition of lipid peroxidation in brain of rats.

Plant Leucine Aminopeptidases Moonlight as Molecular Chaperones to Alleviate Stress-induced Damage*

PubMed Central

Scranton, Melissa A.; Yee, Ashley; Park, Sang-Youl; Walling, Linda L.

2012-01-01

Leucine aminopeptidases (LAPs) are present in animals, plants, and microbes. In plants, there are two classes of LAPs. The neutral LAPs (LAP-N and its orthologs) are constitutively expressed and detected in all plants, whereas the stress-induced acidic LAPs (LAP-A) are expressed only in a subset of the Solanaceae. LAPs have a role in insect defense and act as a regulator of the late branch of wound signaling in Solanum lycopersicum (tomato). Although the mechanism of LAP-A action is unknown, it has been presumed that LAP peptidase activity is essential for regulating wound signaling. Here we show that plant LAPs are bifunctional. Using three assays to monitor protein protection from heat-induced damage, it was shown that the tomato LAP-A and LAP-N and the Arabidopsis thaliana LAP1 and LAP2 are molecular chaperones. Assays using LAP-A catalytic site mutants demonstrated that LAP-A chaperone activity was independent of its peptidase activity. Furthermore, disruption of the LAP-A hexameric structure increased chaperone activity. Together, these data identify a new class of molecular chaperones and a new function for the plant LAPs as well as suggesting new mechanisms for LAP action in the defense of solanaceous plants against stress. PMID:22493451

Anti-inflammatory activity of Polygonum bistorta, Guaiacum officinale and Hamamelis virginiana in rats.

PubMed

Duwiejua, M; Zeitlin, I J; Waterman, P G; Gray, A I

1994-04-01

The aqueous ethanolic extracts of Polygonum bistorta L. Polygonaceae, Guaiacum officinale L. Zygophyllaceae and Hamamelis virginiana L. Hamamelidaceae were screened for anti-inflammatory activity. Administered (100 and 200 mg kg-1, p.o.) before the induction of carrageenan rat paw oedema, extracts of P. bistorta significantly suppressed both the maximal oedema response and the total oedema response (monitored as area under the time course curve). H. virginiana was inactive and G. officinale was only active at 200 mg kg-1. At 200 mg kg-1 administered before the induction of adjuvant arthritis, P. bistorta significantly inhibited both the acute and chronic phases of the adjuvant-induced rat paw swelling, while G. officinale and H. virginiana were only active against the chronic phase. Further studies on P. bistorta (100-800 mg kg-1) revealed a dose-dependent inhibition of the carrageenan-induced rat paw oedema over the dose range 100-400 mg kg-1, the E50 value being approximately 158.5 mg kg-1. The extract (200 mg kg-1), administered after the onset of the inflammatory responses reversed the course of both the carrageenan- and adjuvant-induced rat paw swelling. The results confirm that the extracts of P. bistorta, G. officinale and H. virginiana contain anti-inflammatory substances.

Calcium mobilization and phosphoinositide turnover in fluoride-activated human neutrophils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strnad, C.F.; Wong, K.

1986-05-01

Fluoride ion, at concentrations above 10 mM, has been found to activate a superoxide production response in human neutrophils which is strongly dependent on the presence of extracellular calcium. In an attempt to further explore the calcium requirement of fluoride-induced neutrophil activation, intracellular calcium concentrations were monitored through use of the fluorescent calcium probe, Quin 2. Fluoride ion, at concentrations between 10 and 20 mM, was found to elicit a rise in intracellular calcium levels which was characterized by a lag period of 4 to 10 min and a prolonged duration of action (greater than 20 min). In contrast, themore » chemotactic peptide, formylmethionyl-leucyl-phenylalanine (FMLP), induced a rise in intracellular calcium concentration which peaked within 1 min. Preincubation of cells with 1 ..mu..g/ml pertussis toxin resulted in inhibition of the FMLP-induced response, but not that elicited by fluoride. Furthermore, anion exchange chromatography indicated that inositol phosphate accumulation occurred in fluoride-treated cells in association with calcium mobilization. Recent evidence suggests that the FMLP receptor is coupled to phospholipase C and phosphoinositide turnover through a guanine nucleotide binding protein susceptible to inhibition by pertussis toxin. Present results suggest that fluoride ion may serve to activate this protein in a manner resistant to inhibition by pertussis toxin.« less

Recent Activities on the Embrace Space Weather Regional Warning Center: the New Space Weather Data Center

NASA Astrophysics Data System (ADS)

Denardini, Clezio Marcos; Dal Lago, Alisson; Mendes, Odim; Batista, Inez S.; SantAnna, Nilson; Gatto, Rubens; Takahashi, Hisao; Costa, D. Joaquim; Banik Padua, Marcelo; Campos Velho, Haroldo

2016-07-01

On August 2007 the National Institute for Space Research started a task force to develop and operate a space weather program, which is known by the acronyms Embrace that stands for the Portuguese statement "Estudo e Monitoramento BRAasileiro de Clima Espacial" Program (Brazilian Space Weather Study and Monitoring program). The mission of the Embrace/INPE program is to monitor the Solar-Terrestrial environment, the magnetosphere, the upper atmosphere and the ground induced currents to prevent effects on technological and economic activities. The Embrace/INPE system monitors the physical parameters of the Sun-Earth environment, such as Active Regions (AR) in the Sun and solar radiation by using radio telescope, Coronal Mass Ejection (CME) information by satellite and ground-based cosmic ray monitoring, geomagnetic activity by the magnetometer network, and ionospheric disturbance by ionospheric sounders and using data collected by four GPS receiver network, geomagnetic activity by a magnetometer network, and provides a forecasting for Total Electronic Content (TEC) - 24 hours ahead - using a version of the SUPIM model which assimilates the two latter data using nudging approach. Most of these physical parameters are daily published on the Brazilian space weather program web portal, related to the entire network sensors available. Regarding outreach, it has being published a daily bulletin in Portuguese and English with the status of the space weather environment on the Sun, the Interplanetary Medium and close to the Earth. Since December 2011, all these activities are carried out at the Embrace Headquarter, a building located at the INPE's main campus. Recently, a comprehensive data bank and an interface layer are under commissioning to allow an easy and direct access to all the space weather data collected by Embrace through the Embrace web Portal. The information being released encompasses data from: (a) the Embrace Digisonde Network (Embrace DigiNet) that monitors the ionospheric profiles in two equatorial sites and in two low latitude sites; (b) several solar radio telescopes to monitor solar activity (under development); (c) the matrix of the GNSS TEC map over South America; (d) the Embrace Airglow All-sky Imagers Network (Embrace GlowNet); and (d) the Embrace Magnetometer Network (Embrace Magnet), all of them in South America. Also, the system allows subscription to space weather alerts and reports. Contacting Author: C. M. Denardini (clezio.denardin@inpe.br)

Fluorescence imaging analysis of taxol-induced ASTC-a-1 cell death with cell swelling and cytoplasmic vacuolization

NASA Astrophysics Data System (ADS)

Chen, Tong-sheng; Sun, Lei; Wang, Longxiang; Wang, Huiying

2008-02-01

Taxol (Paclitaxel), an isolated component from the bark of the Pacific yew Taxus brevifolia, exhibits a broad spectrum of clinical activity against human cancers. Taxol can promote microtubule (MT) assembly, inhibit depolymerization, and change MT dynamics, resulting in disruption of the normal reorganization of the microtubule network required for mitosis and cell proliferation. However, the molecular mechanism of taxol-induced cell death is still unclear. In this report, CCK-8 was used to assay the inhibition of taxol on the human lung adenocarcinoma (ASTC-a-1) cells viability, confocal fluorescence microscope was used to monitor the morphology changes of cells with taxol treatment. We for the first time describe the characteristics of taxol-induced cells swelling, cytoplasmic vacuolization and cell death. Taxol induced swelling, cytoplasmatic vacuolization and cell death without cell shrinkage and membrane rupture. These features differ from those of apoptosis and resemble the paraptosis, a novel nonapoptotic PCD.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Ruizhao, E-mail: liruizhao1979@126.com; Zhang, Li, E-mail: Zhanglichangde@163.com; Southern Medical University, Guangzhou, Guangdong

Background: Hyperglycemia promotes podocyte apoptosis and plays a key role in the pathogenesis of diabetic nephropathy. However, the mechanisms that mediate hyperglycemia-induced podocyte apoptosis is still far from being fully understood. Recent studies reported that high glucose activate nuclear factor of activated T cells (NFAT) in vascular smooth muscle or pancreatic β-cells. Here, we sought to determine if hyperglycemia activates NFAT2 in cultured podocyte and whether this leads to podocyte apoptosis. Meanwhile, we also further explore the mechanisms of NFAT2 activation and NFAT2 mediates high glucose-induced podocyte apoptosis. Methods: Immortalized mouse podocytes were cultured in media containing normal glucose (NG),more » or high glucose (HG) or HG plus cyclosporine A (a pharmacological inhibitor of calcinerin) or 11R-VIVIT (a special inhibitor of NFAT2). The activation of NFAT2 in podocytes was detected by western blotting and immunofluorescence assay. The role of NFAT2 in hyperglycemia-induced podocyte apoptosis was further evaluated by observing the inhibition of NFAT2 activation by 11R-VIVIT using flow cytometer. Intracellular Ca{sup 2+} was monitored in HG-treated podcocytes using Fluo-3/AM. The mRNA and protein expression of apoptosis gene Bax were measured by real time-qPCR and western blotting. Results: HG stimulation activated NFAT2 in a time- and dose-dependent manner in cultured podocytes. Pretreatment with cyclosporine A (500 nM) or 11R-VIVIT (100 nM) completely blocked NFAT2 nuclear accumulation. Meanwhile, the apoptosis effects induced by HG were also abrogated by concomitant treatment with 11R-VIVIT in cultured podocytes. We further found that HG also increased [Ca{sup 2+}]i, leading to activation of calcineurin, and subsequent increased nuclear accumulation of NFAT2 and Bax expression in cultured podocytes. Conclusion: Our results identify a new finding that HG-induced podocyte apoptosis is mediated by calcineurin/NFAT2/Bax signaling pathway, which may present a promising target for therapeutic intervention. - Highlights: ► HG activated NFAT2 in a time- and dose-dependent manner in cultured podocytes. ► Pretreatment with CsA or 11R-VIVIT completely blocked NFAT2 nuclear accumulation. ► The apoptosis effects induced by HG were abrogated by treatment with 11R-VIVIT. ► HG-induced podocyte apoptosis is mediated by calcineurin/NFAT2/Bax signaling pathway.« less

Phenotyping the quality of complex medium components by simple online-monitored shake flask experiments.

PubMed

Diederichs, Sylvia; Korona, Anna; Staaden, Antje; Kroutil, Wolfgang; Honda, Kohsuke; Ohtake, Hisao; Büchs, Jochen

2014-11-07

Media containing yeast extracts and other complex raw materials are widely used for the cultivation of microorganisms. However, variations in the specific nutrient composition can occur, due to differences in the complex raw material ingredients and in the production of these components. These lot-to-lot variations can affect growth rate, product yield and product quality in laboratory investigations and biopharmaceutical production processes. In the FDA's Process Analytical Technology (PAT) initiative, the control and assessment of the quality of critical raw materials is one key aspect to maintain product quality and consistency. In this study, the Respiration Activity Monitoring System (RAMOS) was used to evaluate the impact of different yeast extracts and commercial complex auto-induction medium lots on metabolic activity and product yield of four recombinant Escherichia coli variants encoding different enzymes. Under non-induced conditions, the oxygen transfer rate (OTR) of E. coli was not affected by a variation of the supplemented yeast extract lot. The comparison of E. coli cultivations under induced conditions exhibited tremendous differences in OTR profiles and volumetric activity for all investigated yeast extract lots of different suppliers as well as lots of the same supplier independent of the E. coli variant. Cultivation in the commercial auto-induction medium lots revealed the same reproducible variations. In cultivations with parallel offline analysis, the highest volumetric activity was found at different cultivation times. Only by online monitoring of the cultures, a distinct cultivation phase (e.g. glycerol depletion) could be detected and chosen for comparable and reproducible offline analysis of the yield of functional product. This work proves that cultivations conducted in complex media may be prone to significant variation in final product quality and quantity if the quality of the raw material for medium preparation is not thoroughly checked. In this study, the RAMOS technique enabled a reliable and reproducible screening and phenotyping of complex raw material lots by online measurement of the respiration activity. Consequently, complex raw material lots can efficiently be assessed if the distinct effects on culture behavior and final product quality and quantity are visualized.

Sweet smells prepare plants for future stress: airborne induction of plant disease immunity.

PubMed

Yi, Hwe-Su; Ryu, Choong-Min; Heil, Martin

2010-05-01

Plants require protection against a wide range of attackers such as insects and pathogens. The adequate plant defense responses are regulated via sophisticated signal cascades, which are activated following the perception of specific cues of the attackers. Plants might, however, gain a significant fitness advantage when pre-empting enemy attack before it actually occurs. Monitoring cues from attacked neighbors can permit plants to reach this goal. We have recently found airborne disease resistance against a bacterial pathogen in uninfected lima bean plants when these were located close to conspecific, resistance-expressing neighbors. The emitters could be chemically induced with benzothiadiazole or biologically with an avirulent pathogen. Unexpectedly, receiver plants, although expressing a functioning resistance, did not show reduced growth rates, which represent a common side-effect of directly induced pathogen resistance. Nonanal was identified as an active volatile and, rather than directly inducing full resistance, primed defense gene expression, which became fully activated only when the plants were subsequently challenged by a virulent pathogen. Priming by airborne signals allows for a more efficient and less costly preparation of plants for future attack and airborne signaling can affect resistance against both major groups of plant enemies: herbivores and pathogens.

The anticancer homeopathic composite "Canova Method" is not genotoxic for human lymphocytes in vitro.

PubMed

Seligmann, Igor C; Lima, Patrícia D L; Cardoso, Plínio C S; Khayat, André S; Bahia, Marcelo O; Buchi, Dorli de Freitas; Cabral, Isabel R; Burbano, Rommel R

2003-06-30

The Canova Method (CM) is a homeopathic medicine indicated for the treatment of patients with cancer and for pathologies that involve a depressed immune system, such as AIDS. This product is composed of homeopathic dilutions of Aconitum napellus, Arsenicum album (arsenic trioxide), Bryonia alba, Lachesis muta venom and Thuya occidentalis. It stimulates the immune system by activating macrophages. Activated macrophages stimulate the lymphocytes so that they increase their cytotoxic action in response to tumoral growth or infection. Given that the CM stimulates and accelerates the activity of macrophages and lymphocytes, we evaluated genotoxic effects induced in human lymphocytes treated with this homeopathic medication in vitro. Structural and numerical chromosomal aberrations were scored for the assessment of induced genotoxic effects, while the variation in mitotic index was considered as a monitor for induced cellular toxicity. The lymphocytes were cultivated for 24, 48 or 72 h in the following final concentrations of the medicinal composite CM: 4, 8 and 12%. Treatments with the CM did not affect mitotic indexes, nor did they provoke chromosomal aberrations, when compared with untreated controls. There was no cytotoxicity or genotoxicity at the chromosomal level.

Antioxidant properties and inhibitory effects of Satureja khozestanica essential oil on LDL oxidation induced-CuSO4 in vitro

PubMed Central

Bagheri, Shahrokh; Ahmadvand, Hassan; Khosrowbeygi, Ali; Ghazanfari, Farshid; Jafari, Narges; Nazem, Habibolah; Hosseini, Reza Haji

2013-01-01

Objective To assess various antioxidative activities of Satureja khozestanica essential oil (SKE) and its effect on oxidation of low density lipoprotein (LDL) induced by CuSO4 in vitro by monitoring the formation of conjugated dienes and malondialdehyde (MDA). Methods The formation of conjugated dienes, lag time and MDA were measured. Inhibition of this Cu-induced oxidation was studied in the presence of several concentrations of SKE. Also total antioxidant activity and free radical scavenging of SKE were determinated. Results It was demonstrated that SKE was able to inhibit LDL oxidation and decrease the resistance of LDL against oxidation. The inhibitory effects of SKE on LDL oxidation were dose-dependent at concentrations ranging from 50 to 200 µg/mL. Total antioxidant capacity of SKE was (3.20±0.40) nmol of ascorbic acid equivalents/g SKE. The SKE showed remarkable scavenging activity on 2, 2-diphenyl-picrylhydrazyl, IC50 (5.30±0.11) ng/mL. Conclusions This study shows that SKE is a source of potent antioxidants and prevents the oxidation of LDL in vitro and it may be suitable for use in food and pharmaceutical applications. PMID:23570012

Sorbitol counteracts temperature- and chemical-induced denaturation of a recombinant α-amylase from alkaliphilic Bacillus sp. TS-23.

PubMed

Chi, Meng-Chun; Wu, Tai-Jung; Chen, Hsing-Ling; Lo, Huei-Fen; Lin, Long-Liu

2012-12-01

Enzymes are highly complex systems with a substantial degree of structural variability in their folded state. In the presence of cosolvents, fluctuations among vast numbers of folded and unfolded conformations occur via many different pathways; alternatively, certain conformations can be stabilized or destabilized. To understand the contribution of osmolytes to the stabilization of structural changes and enzymatic activity of a truncated Bacillus sp. TS-23 α-amylase (BACΔNC), we monitored amylolytic activity, circular dichroism, and fluorescence as a function of osmolytes. In the presence of trimethylamine N-oxide (TMAO) and sorbitol, BACΔNC activity was retained significantly at elevated temperatures. As compared to the control, the secondary structures of this enzyme were essentially conserved upon the addition of these two kinds of osmolytes. Fluorescence results revealed that the temperature-induced conformational change of BACΔNC was prevented by TMAO and sorbitol. However, glycerol did not provide profound protection against thermal denaturation of the enzyme. Sorbitol was further found to counteract guanidine hydrochloride- and SDS-induced denaturation of BACΔNC. Thus, some well-known naturally occurring osmolytes make a dominant contribution to the stabilization of BACΔNC.

A simple whole cell based high throughput screening protocol using Mycobacterium bovis BCG for inhibitors against dormant and active tubercle bacilli.

PubMed

Khan, Arshad; Sarkar, Dhiman

2008-04-01

This study aimed at developing a whole cell based high throughput screening protocol to identify inhibitors against both active and dormant tubercle bacilli. A respiratory type of nitrate reductase (NarGHJI), which was induced during dormancy, could reflect the viability of dormant bacilli of Mycobacterium bovis BCG in microplate adopted model of in vitro dormancy. Correlation between reduction in viability and nitrate reductase activity was seen clearly when dormant stage inhibitor metronidazole and itaconic anhydride were applied in this in vitro microplate model. Active replicating stage could also be monitored in the same assay by measuring the A(620) of the culture. MIC values of 0.08, 0.075, 0.3 and 3.0 microg/ml, determined through monitoring A(620) in this assay for rifampin, isoniazid, streptomycin and ethambutol respectively, were well in agreement with previously reported by BACTEC and Bio-Siv assays. S/N ratio and Z' factor for the assay were 8.5 and 0.81 respectively which indicated the robustness of the protocol. Altogether the assay provides an easy, inexpensive, rapid, robust and high content screening tool to search novel antitubercular molecules against both active and dormant bacilli.

Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity.

PubMed

Vogl, Thomas; Eisenblätter, Michel; Völler, Tom; Zenker, Stefanie; Hermann, Sven; van Lent, Peter; Faust, Andreas; Geyer, Christiane; Petersen, Beatrix; Roebrock, Kirsten; Schäfers, Michael; Bremer, Christoph; Roth, Johannes

2014-08-06

Inflammation has a key role in the pathogenesis of various human diseases. The early detection, localization and monitoring of inflammation are crucial for tailoring individual therapies. However, reliable biomarkers to detect local inflammatory activities and to predict disease outcome are still missing. Alarmins, which are locally released during cellular stress, are early amplifiers of inflammation. Here, using optical molecular imaging, we demonstrate that the alarmin S100A8/S100A9 serves as a sensitive local and systemic marker for the detection of even sub-clinical disease activity in inflammatory and immunological processes like irritative and allergic contact dermatitis. In a model of collagen-induced arthritis, we use S100A8/S100A9 imaging to predict the development of disease activity. Furthermore, S100A8/S100A9 can act as a very early and sensitive biomarker in experimental leishmaniasis for phagocyte activation linked to an effective Th1-response. In conclusion, the alarmin S100A8/S100A9 is a valuable and sensitive molecular target for novel imaging approaches to monitor clinically relevant inflammatory disorders on a molecular level.

Hide and Seek: Radial-velocity searches for planets around active stars

NASA Astrophysics Data System (ADS)

Haywood, Raphaelle

2017-01-01

The ultimate obstacle to determining the masses of small, rocky exoplanets through radial-velocity (RV) monitoring is the intrinsic variability of the host stars themselves. For my PhD, I developed an intuitive and robust data analysis framework in which the activity-induced variations are modelled with a Gaussian process that has the frequency structure of the stellar magnetic activity. This allowed me to determine precise and accurate masses of the planets in the CoRoT-7, Kepler-78 and Kepler-10 systems. In parallel, I explored the physical origin of activity-induced RV variations of our best-known star: the Sun. I conducted the first systematic RV campaign of the Sun seen as an exoplanet host star using the 3.6m/HARPS spectrograph, by observing sunlight reflected off the bright asteroid 4/Vesta. I used images from the Solar Dynamics Observatory to reconstruct the RV signals incurred by individual surface features such as sunspots, faculae and granulation. I found that the activity-induced RV variations are driven by the suppression of convective blueshift arising dominantly from the presence of faculae. I also identified the full-disc magnetic flux as an excellent proxy for activity-induced RV variations.I am now pursuing my solar investigations using Sun-as-a-star RV observations acquired with the new solar telescope feed at HARPS-N. In particular, I am investigating the impact of magnetic surface features on the shapes of the spectral line profiles, rather than on the RVs themselves (which are a single moment of these lines). This work is key to developing physically-driven, better-tailored models for activity-induced RV variations, in preparation for the potentially habitable, Earth-like planets to be discovered and characterised in the coming years with TESS and GMT/G-CLEF.This work was funded by the Science and Technology Facilities Council in the United Kingdom and the John Templeton Foundation.

Imposed glutathione-mediated redox switch modulates the tobacco wound-induced protein kinase and salicylic acid-induced protein kinase activation state and impacts on defence against Pseudomonas syringae.

PubMed

Matern, Sanja; Peskan-Berghoefer, Tatjana; Gromes, Roland; Kiesel, Rebecca Vazquez; Rausch, Thomas

2015-04-01

The role of the redox-active tripeptide glutathione in plant defence against pathogens has been studied extensively; however, the impact of changes in cellular glutathione redox potential on signalling processes during defence reactions has remained elusive. This study explored the impact of elevated glutathione content on the cytosolic redox potential and on early defence signalling at the level of mitogen-activated protein kinases (MAPKs), as well as on subsequent defence reactions, including changes in salicylic acid (SA) content, pathogenesis-related gene expression, callose depositions, and the hypersensitive response. Wild-type (WT) Nicotiana tabacum L. and transgenic high-glutathione lines (HGL) were transformed with the cytosol-targeted sensor GRX1-roGFP2 to monitor the cytosolic redox state. Surprisingly, HGLs displayed an oxidative shift in their cytosolic redox potential and an activation of the tobacco MAPKs wound-induced protein kinase (WIPK) and SA-induced protein kinase (SIPK). This activation occurred in the absence of any change in free SA content, but was accompanied by constitutively increased expression of several defence genes. Similarly, rapid activation of MAPKs could be induced in WT tobacco by exposure to either reduced or oxidized glutathione. When HGL plants were challenged with adapted or non-adapted Pseudomonas syringae pathovars, the cytosolic redox shift was further amplified and the defence response was markedly increased, showing a priming effect for SA and callose; however, the initial and transient hyperactivation of MAPK signalling was attenuated in HGLs. The results suggest that, in tobacco, MAPK and SA signalling may operate independently, both possibly being modulated by the glutathione redox potential. Possible mechanisms for redox-mediated MAPK activation are discussed. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Characterizing human activity induced impulse and slip-pulse excitations through structural vibration

NASA Astrophysics Data System (ADS)

Pan, Shijia; Mirshekari, Mostafa; Fagert, Jonathon; Ramirez, Ceferino Gabriel; Chung, Albert Jin; Hu, Chih Chi; Shen, John Paul; Zhang, Pei; Noh, Hae Young

2018-02-01

Many human activities induce excitations on ambient structures with various objects, causing the structures to vibrate. Accurate vibration excitation source detection and characterization enable human activity information inference, hence allowing human activity monitoring for various smart building applications. By utilizing structural vibrations, we can achieve sparse and non-intrusive sensing, unlike pressure- and vision-based methods. Many approaches have been presented on vibration-based source characterization, and they often either focus on one excitation type or have limited performance due to the dispersion and attenuation effects of the structures. In this paper, we present our method to characterize two main types of excitations induced by human activities (impulse and slip-pulse) on multiple structures. By understanding the physical properties of waves and their propagation, the system can achieve accurate excitation tracking on different structures without large-scale labeled training data. Specifically, our algorithm takes properties of surface waves generated by impulse and of body waves generated by slip-pulse into account to handle the dispersion and attenuation effects when different types of excitations happen on various structures. We then evaluate the algorithm through multiple scenarios. Our method achieves up to a six times improvement in impulse localization accuracy and a three times improvement in slip-pulse trajectory length estimation compared to existing methods that do not take wave properties into account.

CGK733-induced LC3 II formation is positively associated with the expression of cyclin-dependent kinase inhibitor p21Waf1/Cip1 through modulation of the AMPK and PERK/CHOP signaling pathways.

PubMed

Wang, Yufeng; Kuramitsu, Yasuhiro; Baron, Byron; Kitagawa, Takao; Tokuda, Kazuhiro; Akada, Junko; Nakamura, Kazuyuki

2015-11-24

Microtubule-associated protein 1A/1B-light chain 3 (LC3)-II is essential for autophagosome formation and is widely used to monitor autophagic activity. We show that CGK733 induces LC3 II and LC3-puncta accumulation, which are not involved in the activation of autophagy. The treatment of CGK733 did not alter the autophagic flux and was unrelated to p62 degradation. Treatment with CGK733 activated the AMP-activated protein kinase (AMPK) and protein kinase RNA-like endoplasmic reticulum kinase/CCAAT-enhancer-binding protein homologous protein (PERK/CHOP) pathways and elevated the expression of p21Waf1/Cip1. Inhibition of both AMPK and PERK/CHOP pathways by siRNA or chemical inhibitor could block CGK733-induced p21Waf1/Cip1 expression as well as caspase-3 cleavage. Knockdown of LC3 B (but not LC3 A) abolished CGK733-triggered LC3 II accumulation and consequently diminished AMPK and PERK/CHOP activity as well as p21Waf1/Cip1 expression. Our results demonstrate that CGK733-triggered LC3 II formation is an initial event upstream of the AMPK and PERK/CHOP pathways, both of which control p21Waf1/Cip1 expression.

Protein-Tyrosine Phosphatase-1B Mediates Sleep Fragmentation-Induced Insulin Resistance and Visceral Adipose Tissue Inflammation in Mice.

PubMed

Gozal, David; Khalyfa, Abdelnaby; Qiao, Zhuanghong; Akbarpour, Mahzad; Maccari, Rosanna; Ottanà, Rosaria

2017-09-01

Sleep fragmentation (SF) is highly prevalent and has emerged as an important contributing factor to obesity and metabolic syndrome. We hypothesized that SF-induced increases in protein tyrosine phosphatase-1B (PTP-1B) expression and activity underlie increased food intake, inflammation, and leptin and insulin resistance. Wild-type (WT) and ObR-PTP-1b-/- mice (Tg) were exposed to SF and control sleep (SC), and food intake was monitored. WT mice received a PTP-1B inhibitor (RO-7d; Tx) or vehicle (Veh). Upon completion of exposures, systemic insulin and leptin sensitivity tests were performed as well as assessment of visceral white adipose tissue (vWAT) insulin receptor sensitivity and macrophages (ATM) polarity. SF increased food intake in either untreated or Veh-treated WT mice. Leptin-induced hypothalamic STAT3 phosphorylation was decreased, PTP-1B activity was increased, and reduced insulin sensitivity emerged both systemic and in vWAT, with the latter displaying proinflammatory ATM polarity changes. All of the SF-induced effects were abrogated following PTP-1B inhibitor treatment and in Tg mice. SF induces increased food intake, reduced leptin signaling in hypothalamus, systemic insulin resistance, and reduced vWAT insulin sensitivity and inflammation that are mediated by increased PTP-1B activity. Thus, PTP-1B may represent a viable therapeutic target in the context of SF-induced weight gain and metabolic dysfunction. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF-κB.

PubMed

Goh, Fera Y; Upton, Nadine; Guan, Shouping; Cheng, Chang; Shanmugam, Muthu K; Sethi, Gautam; Leung, Bernard P; Wong, W S Fred

2012-03-15

Persistent activation of nuclear factor-κB (NF-κB) has been associated with the development of asthma. Fisetin (3,7,3',4'-tetrahydroxyflavone), a naturally occurring bioactive flavonol, has been shown to inhibit NF-κB activity. We hypothesized that fisetin may attenuate allergic asthma via negative regulation of the NF-κB activity. Female BALB/c mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Fisetin dose-dependently inhibited ovalbumin-induced increases in total cell count, eosinophil count, and IL-4, IL-5 and IL-13 levels recovered in bronchoalveolar lavage fluid. It attenuated ovalbumin-induced lung tissue eosinophilia and airway mucus production, mRNA expression of adhesion molecules, chitinase, IL-17, IL-33, Muc5ac and inducible nitric oxide synthase in lung tissues, and airway hyperresponsiveness to methacholine. Fisetin blocked NF-κB subunit p65 nuclear translocation and DNA-binding activity in the nuclear extracts from lung tissues of ovalbumin-challenged mice. In normal human bronchial epithelial cells, fisetin repressed TNF-α-induced NF-κB-dependent reporter gene expression. Our findings implicate a potential therapeutic value of fisetin in the treatment of asthma through negative regulation of NF-κB pathway. Copyright © 2012 Elsevier B.V. All rights reserved.

An extract of Urtica dioica L. mitigates obesity induced insulin resistance in mice skeletal muscle via protein phosphatase 2A (PP2A)

PubMed Central

Obanda, Diana N.; Ribnicky, David; Yu, Yongmei; Stephens, Jacqueline; Cefalu, William T.

2016-01-01

The leaf extract of Urtica dioica L. (UT) has been reported to improve glucose homeostasis in vivo, but definitive studies on efficacy and mechanism of action are lacking. We investigated the effects of UT on obesity- induced insulin resistance in skeletal muscle. Male C57BL/6J mice were divided into three groups: low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with UT. Body weight, body composition, plasma glucose and plasma insulin were monitored. Skeletal muscle (gastrocnemius) was analyzed for insulin sensitivity, ceramide accumulation and the post translational modification and activity of protein phosphatase 2A (PP2A). PP2A is activated by ceramides and dephosphorylates Akt. C2C12 myotubes exposed to excess free fatty acids with or without UT were also evaluated for insulin signaling and modulation of PP2A. The HFD induced insulin resistance, increased fasting plasma glucose, enhanced ceramide accumulation and PP2A activity in skeletal muscle. Supplementation with UT improved plasma glucose homeostasis and enhanced skeletal muscle insulin sensitivity without affecting body weight and body composition. In myotubes, UT attenuated the ability of FFAs to induce insulin resistance and PP2A hyperactivity without affecting ceramide accumulation and PP2A expression. UT decreased PP2A activity through posttranslational modification that was accompanied by a reduction in Akt dephosphorylation. PMID:26916435

Planarians as models of cadmium-induced neoplasia provide measurable benchmarks for mechanistic studies.

PubMed

Voura, Evelyn B; Montalvo, Melissa J; Dela Roca, Kevin T; Fisher, Julia M; Defamie, Virginie; Narala, Swami R; Khokha, Rama; Mulligan, Margaret E; Evans, Colleen A

2017-08-01

Bioassays of planarian neoplasia highlight the potential of these organisms as useful standards to assess whether environmental toxins such as cadmium promote tumorigenesis. These studies complement other investigations into the exceptional healing and regeneration of planarians - processes that are driven by a population of active stem cells, or neoblasts, which are likely transformed during planarian tumor growth. Our goal was to determine if planarian tumorigenesis assays are amenable to mechanistic studies of cadmium carcinogenesis. To that end we demonstrate, by examining both counts of cell populations by size, and instances of mitosis, that the activity of the stem cell population can be monitored. We also provide evidence that specific biomodulators can affect the potential of planarian neoplastic growth, in that an inhibitor of metalloproteinases effectively blocked the development of the lesions. From these results, we infer that neoblast activity does respond to cadmium-induced tumor growth, and that metalloproteinases are required for the progression of cancer in the planarian. Copyright © 2017 Elsevier Inc. All rights reserved.

Feed-drug interaction of orally applied butyrate and phenobarbital on hepatic cytochrome P450 activity in chickens.

PubMed

Mátis, G; Kulcsár, A; Petrilla, J; Hermándy-Berencz, K; Neogrády, Zs

2016-08-01

The expression of hepatic drug-metabolizing cytochrome P450 (CYP) enzymes may be affected by several nutrition-derived compounds, such as by the commonly applied feed additive butyrate, possibly leading to feed-drug interactions. The aim of this study was to provide some evidence if butyrate can alter the activity of hepatic CYPs in chickens exposed to CYP-inducing xenobiotics, monitoring for the first time the possibility of such interaction. Ross 308 chickens in the grower phase were treated with daily intracoelomal phenobarbital (PB) injection (80 mg/kg BW), applied as a non-specific CYP-inducer, simultaneously with two different doses of intra-ingluvial sodium butyrate boluses (0.25 and 1.25 g/kg BW) for 5 days. Activity of CYP2H and CYP3A subfamilies was assessed by specific enzyme assays from isolated liver microsomes. According to our results, the lower dose of orally administered butyrate significantly attenuated the PB-triggered elevation of both hepatic CYP2H and CYP3A activities, which might be in association with the partly common signalling pathways of butyrate and CYP-inducing drugs, such as that of PB. Based on these data, butyrate may take part in pharmacoepigenetic interactions with simultaneously applied drugs or other CYP-inducing xenobiotics, with possible consequences for food safety and pharmacotherapy. Butyrate was found to be capable to maintain physiological CYP activity by attenuating CYP induction, underlining the safety of butyrate application in poultry nutrition. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

Outer Membrane Vesicles Prime and Activate Macrophage Inflammasomes and Cytokine Secretion In Vitro and In Vivo

PubMed Central

Cecil, Jessica D.; O’Brien-Simpson, Neil M.; Lenzo, Jason C.; Holden, James A.; Singleton, William; Perez-Gonzalez, Alexis; Mansell, Ashley; Reynolds, Eric C.

2017-01-01

Outer membrane vesicles (OMVs) are proteoliposomes blebbed from the surface of Gram-negative bacteria. Chronic periodontitis is associated with an increase in subgingival plaque of Gram-negative bacteria, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. In this study, we investigated the immune-modulatory effects of P. gingivalis, T. denticola, and T. forsythia OMVs on monocytes and differentiated macrophages. All of the bacterial OMVs were phagocytosed by monocytes, M(naïve) and M(IFNγ) macrophages in a dose-dependent manner. They also induced NF-κB activation and increased TNFα, IL-8, and IL-1β cytokine secretion. P. gingivalis OMVs were also found to induce anti-inflammatory IL-10 secretion. Although unprimed monocytes and macrophages were resistant to OMV-induced cell death, lipopolysaccharide or OMV priming resulted in a significantly reduced cell viability. P. gingivalis, T. denticola, and T. forsythia OMVs all activated inflammasome complexes, as monitored by IL-1β secretion and ASC speck formation. ASC was critical for OMV-induced inflammasome formation, while AIM2−/− and Caspase-1−/− cells had significantly reduced inflammasome formation and NLRP3−/− cells exhibited a slight reduction. OMVs were also found to provide both priming and activation of the inflammasome complex. High-resolution microscopy and flow cytometry showed that P. gingivalis OMVs primed and activated macrophage inflammasomes in vivo with 80% of macrophages exhibiting inflammasome complex formation. In conclusion, periodontal pathogen OMVs were found to have significant immunomodulatory effects upon monocytes and macrophages and should therefore influence pro-inflammatory host responses associated with disease. PMID:28890719

Stimulation of D2 receptors in the prefrontal cortex reduces PCP-induced hyperactivity, acetylcholine release and dopamine metabolism in the nucleus accumbens.

PubMed

Del Arco, A; Mora, F; Mohammed, A H; Fuxe, K

2007-02-01

The aim of the present study was to investigate the effects of stimulation of D2 receptors in the prefrontal cortex (PFC) on spontaneous motor activity and the hyperactivity induced by the psychomimetic phencyclidine (PCP). In addition, the effects of prefrontal D2 stimulation under PCP treatment on dialysate concentrations of acetylcholine, choline, dopamine, DOPAC and HVA in the nucleus accumbens were also investigated. Sprague-Dawley male rats were implanted with guide cannulae to perform bilateral injections into the medial PFC of the D2 agonist quinpirole (1.5 and 5 microg/side). Horizontal and vertical spontaneous motor activity and the motor activity induced by systemic injections of the PCP (5 mg/kg i.p.) were monitored in the open field. PFC injections of quinpirole (1.5 and 5 microg/side) significantly decreased horizontal and vertical spontaneous motor activity in a dose-related manner. These effects were blocked by the D2 antagonist raclopride (5 microg/side). Microinjections of quinpirole (1.5 and 5 microg/side) into the PFC also significantly attenuated the hyperactivity produced by PCP (5 mg/kg i.p.). PCP also increased dialysate concentrations of acetylcholine, and dopamine metabolites in the nucleus accumbens. These increases were also reduced by injections of quinpirole (5 microg/side) into the PFC. These results suggest that the stimulation of prefrontal D2 receptors plays an inhibitory role in regulating spontaneous and PCP-induced motor activity and also in the neurochemical changes produced by PCP in the nucleus accumbens.

Monitoring microbial growth and activity using spectral induced polarization and low-field nuclear magnetic resonance

NASA Astrophysics Data System (ADS)

Zhang, Chi; Keating, Kristina; Revil, Andre

2015-04-01

Microbes and microbial activities in the Earth's subsurface play a significant role in shaping subsurface environments and are involved in environmental applications such as remediation of contaminants in groundwater and oil fields biodegradation. Stimulated microbial growth in such applications could cause wide variety of changes of physical/chemical properties in the subsurface. It is critical to monitor and determine the fate and transportation of microorganisms in the subsurface during such applications. Recent geophysical studies demonstrate the potential of two innovative techniques, spectral induced polarization (SIP) and low-field nuclear magnetic resonance (NMR), for monitoring microbial growth and activities in porous media. The SIP measures complex dielectric properties of porous media at low frequencies of exciting electric field, and NMR studies the porous structure of geologic media and characterizes fluids subsurface. In this laboratory study, we examined both SIP and NMR responses from bacterial growth suspension as well as suspension mixed with silica sands. We focus on the direct contribution of microbes to the SIP and NMR signals in the absence of biofilm formation or biomineralization. We used Zymomonas mobilis and Shewanella oneidensis (MR-1) for SIP and NMR measurements, respectively. The SIP measurements were collected over the frequency range of 0.1 - 1 kHz on Z. mobilis growth suspension and suspension saturated sands at different cell densities. SIP data show two distinct peaks in imaginary conductivity spectra, and both imaginary and real conductivities increased as microbial density increased. NMR data were collected using both CPMG pulse sequence and D-T2 mapping to determine the T2-distribution and diffusion properties on S. oneidensis suspension, pellets (live and dead), and suspension mixed with silica sands. NMR data show a decrease in the T2-distribution in S. oneidensis suspension saturated sands as microbial density increase. A clear distinction in the T2-distribution and D-T2 plots between live and dead cell pellets was also observed. These results will provide a basis for understanding the effect of microbes within geologic media on SIP and low-field NMR measurements. This research suggests that both SIP and NMR have the potential to monitor microbial growth and activities in the subsurface and could provide spatiotemporal variations in bacterial abundance in porous media.

A preliminary census of engineering activities located in Sicily (Southern Italy) which may "potentially" induce seismicity

NASA Astrophysics Data System (ADS)

Aloisi, Marco; Briffa, Emanuela; Cannata, Andrea; Cannavò, Flavio; Gambino, Salvatore; Maiolino, Vincenza; Maugeri, Roberto; Palano, Mimmo; Privitera, Eugenio; Scaltrito, Antonio; Spampinato, Salvatore; Ursino, Andrea; Velardita, Rosanna

2015-04-01

The seismic events caused by human engineering activities are commonly termed as "triggered" and "induced". This class of earthquakes, though characterized by low-to-moderate magnitude, have significant social and economical implications since they occur close to the engineering activity responsible for triggering/inducing them and can be felt by the inhabitants living nearby, and may even produce damage. One of the first well-documented examples of induced seismicity was observed in 1932 in Algeria, when a shallow magnitude 3.0 earthquake occurred close to the Oued Fodda Dam. By the continuous global improvement of seismic monitoring networks, numerous other examples of human-induced earthquakes have been identified. Induced earthquakes occur at shallow depths and are related to a number of human activities, such as fluid injection under high pressure (e.g. waste-water disposal in deep wells, hydrofracturing activities in enhanced geothermal systems and oil recovery, shale-gas fracking, natural and CO2 gas storage), hydrocarbon exploitation, groundwater extraction, deep underground mining, large water impoundments and underground nuclear tests. In Italy, induced/triggered seismicity is suspected to have contributed to the disaster of the Vajont dam in 1963. Despite this suspected case and the presence in the Italian territory of a large amount of engineering activities "capable" of inducing seismicity, no extensive researches on this topic have been conducted to date. Hence, in order to improve knowledge and correctly assess the potential hazard at a specific location in the future, here we started a preliminary study on the entire range of engineering activities currently located in Sicily (Southern Italy) which may "potentially" induce seismicity. To this end, we performed: • a preliminary census of all engineering activities located in the study area by collecting all the useful information coming from available on-line catalogues; • a detailed compilation of instrumental and historical seismicity, focal mechanisms solutions, multidisciplinary stress indicators, GPS-based ground deformation field, mapped faults, etc by merging data from on-line catalogues with those reported in literature. Finally, for each individual site, we analysed: i) long-term statistic behaviour of instrumental seismicity (magnitude of completeness, seismic release above a threshold magnitude, depth distribution, focal plane solutions); ii) long-term statistic behaviour of historical seismicity (maximum magnitude estimation, recurrence time interval, etc); iii) properties and orientation of faults (length, estimated geological slip, kinematics, etc); iv) regional stress (from borehole, seismological and geological observations) and strain (from GPS-based observations) fields.

Pseudoephedrine/ephedrine shows potent anti-inflammatory activity against TNF-α-mediated acute liver failure induced by lipopolysaccharide/D-galactosamine.

PubMed

Wu, Zhongping; Kong, Xiangliang; Zhang, Tong; Ye, Jin; Fang, Zhaoqin; Yang, Xuejun

2014-02-05

The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production. Copyright © 2013 Elsevier B.V. All rights reserved.

Metformin ameliorates high uric acid-induced insulin resistance in skeletal muscle cells.

PubMed

Yuan, Huier; Hu, Yaqiu; Zhu, Yuzhang; Zhang, Yongneng; Luo, Chaohuan; Li, Zhi; Wen, Tengfei; Zhuang, Wanling; Zou, Jinfang; Hong, Liangli; Zhang, Xin; Hisatome, Ichiro; Yamamoto, Tetsuya; Cheng, Jidong

2017-03-05

Hyperuricemia occurs together with abnormal glucose metabolism and insulin resistance. Skeletal muscle is an important organ of glucose uptake, disposal, and storage. Metformin activates adenosine monophosphate-activated protein kinase (AMPK) to regulate insulin signaling and promote the translocation of glucose transporter type 4 (GLUT4), thereby stimulating glucose uptake to maintain energy balance. Our previous study showed that high uric acid (HUA) induced insulin resistance in skeletal muscle tissue. However, the mechanism of metformin ameliorating UA-induced insulin resistance in muscle cells is unknown and we aimed to determine it. In this study, differentiated C2C12 cells were exposed to UA (15 mg/dl), then reactive oxygen species (ROS) was detected with DCFH-DA and glucose uptake with 2-NBDG. The levels of phospho-insulin receptor substrate 1 (IRS1; Ser307), phospho-AKT (Ser473) and membrane GLUT4 were examined by western blot analysis. The impact of metformin on UA-induced insulin resistance was monitored by adding Compound C, an AMPK inhibitor, and LY294002, a PI3K/AKT inhibitor. Our data indicate that UA can increase ROS production, inhibit IRS1-AKT signaling and insulin-stimulated glucose uptake, and induce insulin resistance in C2C12 cells. Metformin can reverse this process by increasing intracellular glucose uptake and ameliorating UA-induced insulin resistance. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Non-invasive assessment of the reproductive cycle in free-ranging female African elephants (Loxodonta africana) treated with a gonadotropin-releasing hormone (GnRH) vaccine for inducing anoestrus.

PubMed

Benavides Valades, Gabriela; Ganswindt, Andre; Annandale, Henry; Schulman, Martin L; Bertschinger, Henk J

2012-08-25

In southern Africa, various options to manage elephant populations are being considered. Immunocontraception is considered to be the most ethically acceptable and logistically feasible method for control of smaller and confined populations. In this regard, the use of gonadotropin-releasing hormone (GnRH) vaccine has not been investigated in female elephants, although it has been reported to be safe and effective in several domestic and wildlife species. The aims of this study were to monitor the oestrous cycles of free-ranging African elephant cows using faecal progestagen metabolites and to evaluate the efficacy of a GnRH vaccine to induce anoestrus in treated cows. Between May 2009-June 2010, luteal activity of 12 elephant cows was monitored non-invasively using an enzyme immunoassay detecting faecal 5alpha-reduced pregnanes (faecal progestagen metabolites, FPM) on a private game reserve in South Africa. No bulls of breeding age were present on the reserve prior to and for the duration of the study. After a 3-month control period, 8 randomly-selected females were treated twice with 600 micrograms of GnRH vaccine (Improvac®, Pfizer Animal Health, Sandton, South Africa) 5-7 weeks apart. Four of these females had been treated previously with the porcine zona pellucida (pZP) vaccine for four years (2004-2007). All 12 monitored females (8 treated and 4 controls) showed signs of luteal activity as evidenced by FPM concentrations exceeding individual baseline values more than once. A total of 16 oestrous cycles could be identified in 8 cows with four of these within the 13 to 17 weeks range previously reported for captive African elephants. According to the FPM concentrations the GnRH vaccine was unable to induce anoestrus in the treated cows. Overall FPM levels in samples collected during the wet season (mean 4.03 micrograms/gram dry faeces) were significantly higher (P<0.002) than the dry season (mean 2.59 micrograms/gram dry faeces). The GnRH vaccination protocol failed to induce anoestrus in the treated female elephants. These results indicate that irregular oestrous cycles occur amongst free-ranging elephants and are not restricted to elephants in captivity. The relationship between ecological conditions and endocrine activity were confirmed. Free-ranging female elephants were observed to not cycle continuously throughout the year in the absence of adult bulls.

Cytoplasmic sequestration of cyclin D1 associated with cell cycle withdrawal of neuroblastoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sumrejkanchanakij, Piyamas; Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330; Eto, Kazuhiro

2006-02-03

The regulation of D-type cyclin-dependent kinase activity is critical for neuronal differentiation and apoptosis. We recently showed that cyclin D1 is sequestered in the cytoplasm and that its nuclear localization induces apoptosis in postmitotic primary neurons. Here, we further investigated the role of the subcellular localization of cyclin D1 in cell cycle withdrawal during the differentiation of N1E-115 neuroblastoma cells. We show that cyclin D1 became predominantly cytoplasmic after differentiation. Targeting cyclin D1 expression to the nucleus induced phosphorylation of Rb and cdk2 kinase activity. Furthermore, cyclin D1 nuclear localization promoted differentiated N1E-115 cells to reenter the cell cycle, amore » process that was inhibited by p16{sup INK4a}, a specific inhibitor of D-type cyclin activity. These results indicate that cytoplasmic sequestration of cyclin D1 plays a role in neuronal cell cycle withdrawal, and suggests that the abrogation of machinery involved in monitoring aberrant nuclear cyclin D1 activity contributes to neuronal tumorigenesis.« less

Cytoplasmic sequestration of cyclin D1 associated with cell cycle withdrawal of neuroblastoma cells.

PubMed

Sumrejkanchanakij, Piyamas; Eto, Kazuhiro; Ikeda, Masa-Aki

2006-02-03

The regulation of D-type cyclin-dependent kinase activity is critical for neuronal differentiation and apoptosis. We recently showed that cyclin D1 is sequestered in the cytoplasm and that its nuclear localization induces apoptosis in postmitotic primary neurons. Here, we further investigated the role of the subcellular localization of cyclin D1 in cell cycle withdrawal during the differentiation of N1E-115 neuroblastoma cells. We show that cyclin D1 became predominantly cytoplasmic after differentiation. Targeting cyclin D1 expression to the nucleus induced phosphorylation of Rb and cdk2 kinase activity. Furthermore, cyclin D1 nuclear localization promoted differentiated N1E-115 cells to reenter the cell cycle, a process that was inhibited by p16(INK4a), a specific inhibitor of D-type cyclin activity. These results indicate that cytoplasmic sequestration of cyclin D1 plays a role in neuronal cell cycle withdrawal, and suggests that the abrogation of machinery involved in monitoring aberrant nuclear cyclin D1 activity contributes to neuronal tumorigenesis.

Longitudinal, transcranial measurement of functional activation in the rat brain by diffuse correlation spectroscopy.

PubMed

Blanco, Igor; Zirak, Peyman; Dragojević, Tanja; Castellvi, Clara; Durduran, Turgut; Justicia, Carles

2017-10-01

Neural activity is an important biomarker for the presence of neurodegenerative diseases, cerebrovascular alterations, and brain trauma; furthermore, it is a surrogate marker for treatment effects. These pathologies may occur and evolve in a long time-period, thus, noninvasive, transcutaneous techniques are necessary to allow a longitudinal follow-up. In the present work, we have customized noninvasive, transcutaneous, diffuse correlation spectroscopy (DCS) to localize changes in cerebral blood flow (CBF) induced by neural activity. We were able to detect changes in CBF in the somatosensory cortex by using a model of electrical forepaw stimulation in rats. The suitability of DCS measurements for longitudinal monitoring was demonstrated by performing multiple sessions with the same animals at different ages (from 6 to 18 months). In addition, functional DCS has been cross-validated by comparison with functional magnetic resonance imaging (fMRI) in the same animals in a subset of the time-points. The overall results obtained with transcutaneous DCS demonstrates that it can be utilized in longitudinal studies safely and reproducibly to locate changes in CBF induced by neural activity in the small animal brain.

Review: Some low-frequency electrical methods for subsurface characterization and monitoring in hydrogeology

NASA Astrophysics Data System (ADS)

Revil, A.; Karaoulis, M.; Johnson, T.; Kemna, A.

2012-06-01

Low-frequency geoelectrical methods include mainly self-potential, resistivity, and induced polarization techniques, which have potential in many environmental and hydrogeological applications. They provide complementary information to each other and to in-situ measurements. The self-potential method is a passive measurement of the electrical response associated with the in-situ generation of electrical current due to the flow of pore water in porous media, a salinity gradient, and/or the concentration of redox-active species. Under some conditions, this method can be used to visualize groundwater flow, to determine permeability, and to detect preferential flow paths. Electrical resistivity is dependent on the water content, the temperature, the salinity of the pore water, and the clay content and mineralogy. Time-lapse resistivity can be used to assess the permeability and dispersivity distributions and to monitor contaminant plumes. Induced polarization characterizes the ability of rocks to reversibly store electrical energy. It can be used to image permeability and to monitor chemistry of the pore water-minerals interface. These geophysical methods, reviewed in this paper, should always be used in concert with additional in-situ measurements (e.g. in-situ pumping tests, chemical measurements of the pore water), for instance through joint inversion schemes, which is an area of fertile on-going research.

Induced environment contamination monitor: Preliminary results from the Spacelab 1 flight

NASA Technical Reports Server (NTRS)

Miller, E. R. (Editor)

1984-01-01

The STS-9/Induced Environment Contamination Monitor (IECM) mission is briefly described. Preliminary results and analyses are given for each of the 10 instruments comprising the IECM. The final section presents a summary of the major results.

Dynamic Changes in Cytosolic ATP Levels in Cultured Glutamatergic Neurons During NMDA-Induced Synaptic Activity Supported by Glucose or Lactate.

PubMed

Lange, Sofie C; Winkler, Ulrike; Andresen, Lars; Byhrø, Mathilde; Waagepetersen, Helle S; Hirrlinger, Johannes; Bak, Lasse K

2015-12-01

We have previously shown that synaptic transmission fails in cultured neurons in the presence of lactate as the sole substrate. Thus, to test the hypothesis that the failure of synaptic transmission is a consequence of insufficient energy supply, ATP levels were monitored employing the ATP biosensor Ateam1.03YEMK. While inducing synaptic activity by subjecting cultured neurons to two 30 s pulses of NMDA (30 µM) with a 4 min interval, changes in relative ATP levels were measured in the presence of lactate (1 mM), glucose (2.5 mM) or the combination of the two. ATP levels reversibly declined following NMDA-induced neurotransmission activity, as indicated by a reversible 10-20 % decrease in the response of the biosensor. The responses were absent when the NMDA receptor antagonist memantine was present. In the presence of lactate alone, the ATP response dropped significantly more than in the presence of glucose following the 2nd pulse of NMDA (approx. 10 vs. 20 %). Further, cytosolic Ca(2+) homeostasis during NMDA-induced synaptic transmission is partially inhibited by verapamil indicating that voltage-gated Ca(2+) channels are activated. Lastly, we showed that cytosolic Ca(2+) homeostasis is supported equally well by both glucose and lactate, and that a pulse of NMDA causes accumulation of Ca(2+) in the mitochondrial matrix. In summary, we have shown that ATP homeostasis during neurotransmission activity in cultured neurons is supported by both glucose and lactate. However, ATP homeostasis seems to be negatively affected by the presence of lactate alone, suggesting that glucose is needed to support neuronal energy metabolism during activation.

Anti-inflammatory effects of phytosteryl ferulates in colitis induced by dextran sulphate sodium in mice

PubMed Central

Islam, M S; Murata, T; Fujisawa, M; Nagasaka, R; Ushio, H; Bari, A M; Hori, M; Ozaki, H

2008-01-01

Background and purpose: We have recently reported that phytosteryl ferulates isolated from rice bran inhibit nuclear factor-κB (NF-κB) activity in macrophages. In the present study, we investigated the effect of γ-oryzanol (γ-ORZ), a mixture of phytosteryl ferulates, cycloartenyl ferulate (CAF), one of the components of γ-ORZ, and ferulic acid (FA), a possible metabolite of γ-ORZ in vivo, on a model of colitis in mice. Experimental approach: We induced colitis with dextran sulphate sodium (DSS) in mice and monitored disease activity index (DAI), histopathology score, tissue myeloperoxidase (MPO) activity, mRNA expressions of cytokines and COX-2, colon length, antioxidant potency and NF-κB activity in colitis tissue. Key results: Both DAI and histopathology score revealed that DSS induced a severe mucosal colitis, with a marked increase in the thickness of the muscle layer, distortion and loss of crypts, depletion of goblet cells and infiltration of macrophages, granulocytes and lymphocytes. MPO activity, pro-inflammatory cytokines and COX-2 levels, NF-κB p65 nuclear translocation and inhibitory protein of nuclear factor-κB-α degradation levels were significantly increased in DSS-induced colitis tissues. γ-ORZ (50 mg kg−1 day−1 p.o.) markedly inhibited these inflammatory reactions and CAF had a similar potency. In vitro assay demonstrated that γ-ORZ and CAF had strong antioxidant effects comparable to those of α-tocopherol. Conclusions and implications: Phytosteryl ferulates could be new potential therapeutic and/or preventive agents for gastrointestinal inflammatory diseases. Their anti-inflammatory effect could be mediated by inhibition of NF-κB activity, which was at least partly due to the antioxidant effect of the FA moiety in the structure of phytosteryl ferulates. PMID:18536734

The G2 block induced by DNA damage: a caffeine-resistant component independent of Cdc25C, MPM-2 phosphorylation, and H1 kinase activity.

PubMed

Barratt, R A; Kao, G; McKenna, W G; Kuang, J; Muschel, R J

1998-06-15

Treatment of cells with agents that cause DNA damage often results in a delay in G2. There is convincing evidence showing that inhibition of p34cdc2 kinase activation is involved in the DNA damage-induced G2 delay. In this study, we have demonstrated the existence of an additional pathway, independent of the p34cdc2 kinase activation pathway, that leads to a G2 arrest in etoposide-treated cells. Both the X-ray-induced and the etoposide-induced G2 arrest were associated with inhibition of the p34cdc2 H1 kinase activation pathway as judged by p34cdc2 H1 kinase activity and phosphorylation of cdc25C. Caffeine treatment restored these activities after either of the treatments. However, the etoposide-treated cells did not resume cycling, revealing the presence of an alternative pathway leading to a G2 arrest. To explore the possibility that this additional pathway involved phosphorylation of the MPM-2 epitope that is shared by a large family of mitotic phosphoproteins, we monitored the phosphorylation status of the MPM-2 epitope after DNA damage and after treatment with caffeine. Phosphorylation of the MPM-2 epitope was depressed in both X-ray and etoposide-treated cells, and the depression was reversed by caffeine in both cases. The results indicate that the pathway affecting MPM-2 epitope phosphorylation is involved in the G2 delay caused by DNA damage. However, it is not part of the caffeine-insensitive pathway leading to a G2 block seen in etoposide-treated cells.

[Neuroimaging and the neurobiology of obsessive-compulsive disorder].

PubMed

Schiepek, Günter; Tominschek, Igor; Karch, Susanne; Mulert, Christoph; Pogarell, Oliver

2007-01-01

The following review is focusing on results of functional neuroimaging. After some introductory remarks on the phenomenology, epidemiology, and psychotherapy approaches of obsessive-compulsive disorders (OCD) the most important OCD-related brain regions are presented. Obviously, not only the prominent cortico-striato-thalamo-cortical feedback loops are involved, as functional brain imaging studies tell us, but also other regions as the inferior parietal lobe, the anterior and posterior cingulate gyrus, insula, amygdala, cerebellum, and others. Subclassifications using factor-analysis methods support the hypothesis, that most important subtypes ("washing/contamination fear", "obsessions/checking", "symmetry/ordering", "hoarding") involve different, but partially overlapping brain areas. Stimulation paradigms in fMRI-research are commonly based on symptom provocation by visual or tactile stimuli, or on action-monitoring and error-monitoring tasks. Deficits in action-monitoring and planning are discussed to be one of the basic dysfunctions of OCD. Finally, results of psychotherapeutic induced variations of brain activations in OCD are presented.

DS Sentry: an acquisition ASIC for smart, micro-power sensing applications

NASA Astrophysics Data System (ADS)

Liobe, John; Fiscella, Mark; Moule, Eric; Balon, Mark; Bocko, Mark; Ignjatovic, Zeljko

2011-06-01

Unattended ground monitoring that combines seismic and acoustic information can be a highly valuable tool in intelligence gathering; however there are several prerequisites for this approach to be viable. The first is high sensitivity as well as the ability to discriminate real threats from noise and other spurious signals. By combining ground sensing with acoustic and image monitoring this requirement may be achieved. Moreover, the DS Sentry®provides innate spurious signal rejection by the "active-filtering" technique employed as well as embedding some basic statistical analysis. Another primary requirement is spatial and temporal coverage. The ideal is uninterrupted, long-term monitoring of an area. Therefore, sensors should be densely deployed and consume very little power. Furthermore, sensors must be inexpensive and easily deployed to allow dense placements in critical areas. The ADVIS DS Sentry®, which is a fully-custom integrated circuit that enables smart, micro-power monitoring of dynamic signals, is the foundation of the proposed system. The core premise behind this technology is the use of an ultra-low power front-end for active monitoring of dynamic signals in conjunction with a highresolution, Σ Δ-based analog-to-digital converter, which utilizes a novel noise rejection technique and is only employed when a potential threat has been detected. The DS Sentry® can be integrated with seismic accelerometers and microphones and user-programmed to continuously monitor for signals with specific signatures such as impacts, footsteps, excavation noise, vehicle-induced ground vibrations, or speech, while consuming only microwatts of power. This will enable up to several years of continuous monitoring on a single small battery while concurrently mitigating false threats.

Use of electromagnetic induction methods to monitor remediation at the University of Connecticut landfill: 2004–2011

USGS Publications Warehouse

Johnson, Carole D.; White, Eric A.; Joesten, Peter K.

2012-01-01

Time‐lapse geophysical surveys using frequency‐domain electromagnetics (FDEM) can indirectly measure time‐varying hydrologic parameters such as fluid saturation or solute concentration. Monitoring of these processes provides insight into aquifer properties and the effectiveness of constructed controls (such as leachate interceptor trenches), as well as aquifer responses to natural or induced stresses. At the University of Connecticut landfill, noninvasive, electromagnetic induction (EMI) methods were used to monitor changes in subsurface electrical conductivity that were related to the landfill‐closure activities. After the landfill was closed, EMI methods were used to monitor changes in water saturation and water quality. As part of a long‐term monitoring plan to observe changes associated with closure, redevelopment, and remediation of the former landfill, EMI data were collected to supplement information from groundwater samples collected in wells to the south and north of the landfill. In comparison to single‐point measurements that could have been collected by conventional installation of additional monitoring wells, the EMI methods provided increased spatial coverage, and were less invasive and therefore less destructive to the wetland north of the landfill. To monitor effects of closure activities on the subsurface conductivity, EMI measurements were collected from 2004 to 2011 along discrete transects north and south of the landfill prior to, during, and after the landfill closure. In general, the results indicated an overall decline in subsurface electrical conductivity with time and with distance from the former landfill. This decline in electrical conductivity indicated that the closure and remediation efforts reduced the amount of leachate that originated from the landfill and that entered the drainages to the north and south of the landfill.

The Hollin Hill Landslide Observatory - a decade of geophysical characterization and monitoring

NASA Astrophysics Data System (ADS)

Uhlemann, S.; Wilkinson, P. B.; Meldrum, P.; Smith, A.; Dixon, N.; Merritt, A.; Swift, R. T.; Whiteley, J.; Gunn, D.; Chambers, J. E.

2017-12-01

Landslides are major and frequent natural hazards. They shape the Earth's surface, and endanger communities and infrastructure worldwide. Within the last decade, landslides caused more than 28,000 fatalities and direct damage exceeding $1.8 billion. Climate change, causing more frequent weather extremes, is likely to increase occurrences of shallow slope failures worldwide. Thus, there is a need to improve our understanding of these shallow, rainfall-induced landslides. In this context, integrated geophysical characterization and monitoring can play a crucial role by providing volumetric data that can be linked to the hydrological and geotechnical conditions of a slope. This enables understanding of the complex hydrological processes most-often being associated with landslides. Here we present a review of a decade of characterizing and monitoring a complex, inland, clayey landslide - forming the "Hollin Hill Landslide Observatory". Within the last decade, this landslide has experienced different activity characteristics, including creep, flow, and rotational failures - thereby providing an excellent testbed for the development of geophysical and geotechnical monitoring instrumentation and methodologies. These include developments of 4D geoelectrical monitoring techniques to estimate electrode positions from the resistivity data, incorporating these into a time-lapse inversion, and imaging moisture dynamics that control the landslide behaviour. Other developments include acoustic emission monitoring, and active and passive seismic monitoring. This work is underpinned by detailed characterization of the landslide, using geomorphological and geological mapping, geotechnical investigations, and a thorough geoelectrical and seismic characterization of the landslide mass. Hence, the data gained from the Hollin Hill landslide observatory has improved our understanding of the shallow landslide dynamics in response to climate change, their mechanics and evolution. The methodological and technical developments achieved at this site are suitable and applicable for implementation on other landslides worldwide.

Effects of Pharmacological Inhibition and Genetic Deficiency of Plasminogen Activator Inhibitor-1 in Radiation-Induced Intestinal Injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abderrahmani, Rym; Francois, Agnes; Buard, Valerie

2009-07-01

Purpose: To investigate effects of plasminogen activator inhibitor 1 (PAI-1) genetic deficiency and pharmacological PAI-1 inhibition with PAI-039 in a mouse model of radiation-induced enteropathy. Methods and Materials: Wild-type (Wt) and PAI-1{sup -/-} knockout mice received a single dose of 19 Gy to an exteriorized localized intestinal segment. Sham and irradiated Wt mice were treated orally with 1 mg/g of PAI-039. Histological modifications were quantified using a radiation injury score. Moreover, intestinal gene expression was monitored by real-time PCR. Results: At 3 days after irradiation, PAI-039 abolished the radiation-induced increase in the plasma active form of PAI-1 and limited themore » radiation-induced gene expression of transforming growth factor {beta}1 (TGF-{beta}1), CTGF, PAI-1, and COL1A2. Moreover, PAI-039 conferred temporary protection against early lethality. PAI-039 treatment limited the radiation-induced increase of CTGF and PAI-1 at 2 weeks after irradiation but had no effect at 6 weeks. Radiation injuries were less severe in PAI-1{sup -/-} mice than in Wt mice, and despite the beneficial effect, 3 days after irradiation, PAI-039 had no effects on microscopic radiation injuries compared to untreated Wt mice. Conclusions: A genetic deficiency of PAI-1 is associated with amelioration of late radiation enteropathy. Pharmacological inhibition of PAI-1 by PAI-039 positively impacts the early, acute phase increase in plasma PAI-1 and the associated radiation-induced gene expression of inflammatory/extracellular matrix proteins. Since PAI-039 has been shown to inhibit the active form of PAI-1, as opposed to the complete loss of PAI-1 in the knockout animals, these data suggest that a PAI-1 inhibitor could be beneficial in treating radiation-induced tissue injury in acute settings where PAI-1 is elevated.« less

Actigraphy-based sleep parameters during the reinstatement of methamphetamine self-administration in rhesus monkeys.

PubMed

Berro, Laís F; Andersen, Monica L; Tufik, Sergio; Howell, Leonard L

2016-04-01

The objective of this study was to investigate nighttime activity of nonhuman primates during extinction and cue- and drug-primed reinstatement of methamphetamine self-administration. Adult rhesus monkeys (Macaca mulatta; n = 5) self-administered methamphetamine (0.01 mg/kg/injection, i.v.) under a fixed-ratio 20 schedule of reinforcement. Saline infusions were then substituted for methamphetamine and stimulus light (drug-conditioned stimulus presented during drug self-administration) withheld until subjects reached extinction criteria. Drug- and cue-induced reinstatement effects were evaluated after i.v. noncontingent priming injections of methamphetamine (0.03, 0.1, or 0.3 mg/kg). Activity-based sleep measures were evaluated with Actiwatch monitors a week before (baseline nighttime activity parameters) and throughout the protocol. Although methamphetamine self-administration did not significantly affect nighttime activity compared to baseline, sleeplike parameters were improved during extinction compared to self-administration maintenance. Priming injection of 0.1 mg/kg methamphetamine, but not 0.03 or 0.3 mg/kg, induced significant reinstatement effects. These behavioral responses were accompanied by nighttime outcomes, with increased sleep fragmentation and decreased sleep efficiency in the night following 0.1 mg/kg methamphetamine-induced reinstatement. In the absence of both drug and drug-paired cues (extinction conditions), nighttime activity decreased compared to self-administration maintenance. Additionally, effective reinstatement conditions impaired sleeplike measures. Our data indicate that the reintroduction of the stimulus light as a drug-paired cue increased nighttime activity. (c) 2016 APA, all rights reserved).

Sulfonation and anticoagulant activity of botryosphaeran from Botryosphaeria rhodina MAMB-05 grown on fructose.

PubMed

Mendes, Simone Ferreira; dos Santos, Osvaldo; Barbosa, Aneli M; Vasconcelos, Ana Flora D; Aranda-Selverio, Gabriel; Monteiro, Nilson K; Dekker, Robert F H; Sá Pereira, Mariana; Tovar, Ana Maria F; Mourão, Paulo A de Souza; da Silva, Maria de Lourdes Corradi

2009-10-01

Botryosphaeran (EPS(FRU)), an exopolysaccharide of the beta-(1-->3,1-->6)-d-glucan type with 31% branching at C-6, is produced by the fungus Botryosphaeria rhodina MAMB-05 when grown on fructose as carbon source. Botryosphaeran was derivatized by sulfonation to induce anticoagulant activity. The effectiveness of the sulfonation reaction by chlorosulfonic acid in pyridine was monitored by the degree of substitution and FT-IR analysis of the sulfonated EPS(FRU) (once sulfonated, EPS(FRUSULF); and re-sulfonated, EPS(FRURESULF)). Activated partial thromboplastin time (APTT) and thrombin time (TT) tests of EPS(FRURESULF) indicated significant in vitro anticoagulant activity that was dose-dependent. EPS(FRU) did not inhibit any of the coagulation tests.

Suggested Best Practice for seismic monitoring and characterization of non-conventional reservoirs

NASA Astrophysics Data System (ADS)

Malin, P. E.; Bohnhoff, M.; terHeege, J. H.; Deflandre, J. P.; Sicking, C.

2017-12-01

High rates of induced seismicity and gas leakage in non-conventional production have become a growing issue of public concern. It has resulted in calls for independent monitoring before, during and after reservoir production. To date no uniform practice for it exists and few reservoirs are locally monitored at all. Nonetheless, local seismic monitoring is a pre-requisite for detecting small earthquakes, increases of which can foreshadow damaging ones and indicate gas leaks. Appropriately designed networks, including seismic reflection studies, can be used to collect these and Seismic Emission Tomography (SET) data, the latter significantly helping reservoir characterization and exploitation. We suggest a Step-by-Step procedure for implementing such networks. We describe various field kits, installations, and workflows, all aimed at avoiding damaging seismicity, as indicators of well stability, and improving reservoir exploitation. In Step 1, a single downhole seismograph is recommended for establishing baseline seismicity before development. Subsequent Steps are used to decide cost-effective ways of monitoring treatments, production, and abandonment. We include suggestions for monitoring of disposal and underground storage. We also describe how repeated SET observations improve reservoir management as well as regulatory monitoring. Moreover, SET acquisition can be included at incremental cost in active surveys or temporary passive deployments.

Spatially and temporally resolved gas distributions around heterogeneous catalysts using infrared planar laser-induced fluorescence

PubMed Central

Zetterberg, Johan; Blomberg, Sara; Gustafson, Johan; Evertsson, Jonas; Zhou, Jianfeng; Adams, Emma C.; Carlsson, Per-Anders; Aldén, Marcus; Lundgren, Edvin

2015-01-01

Visualizing and measuring the gas distribution in close proximity to a working catalyst is crucial for understanding how the catalytic activity depends on the structure of the catalyst. However, existing methods are not able to fully determine the gas distribution during a catalytic process. Here we report on how the distribution of a gas during a catalytic reaction can be imaged in situ with high spatial (400 μm) and temporal (15 μs) resolution using infrared planar laser-induced fluorescence. The technique is demonstrated by monitoring, in real-time, the distribution of carbon dioxide during catalytic oxidation of carbon monoxide above powder catalysts. Furthermore, we demonstrate the versatility and potential of the technique in catalysis research by providing a proof-of-principle demonstration of how the activity of several catalysts can be measured simultaneously, either in the same reactor chamber, or in parallel, in different reactor tubes. PMID:25953006

Performing music can induce greater modulation of emotion-related psychophysiological responses than listening to music.

PubMed

Nakahara, Hidehiro; Furuya, Shinichi; Masuko, Tsutomu; Francis, Peter R; Kinoshita, Hiroshi

2011-09-01

The present study investigated the differential effects of music-induced emotion on heart rate (HR) and its variability (HRV) while playing music on the piano and listening to a recording of the same piece of music. Sixteen pianists were monitored during tasks involving emotional piano performance, non-emotional piano performance, emotional perception, and non-emotional perception. It was found that emotional induction during both perception and performance modulated HR and HRV, and that such modulations were significantly greater during musical performance than during perception. The results confirmed that musical performance was far more effective in modulating emotion-related autonomic nerve activity than musical perception in musicians. The findings suggest the presence of a neural network of reward-emotion-associated autonomic nerve activity for musical performance that is independent of a neural network for musical perception. Copyright © 2011 Elsevier B.V. All rights reserved.

Preliminary evaluation of in vitro cytotoxicity and in vivo antitumor activity of Xanthium strumarium in transplantable tumors in mice.

PubMed

Aranjani, Jesil Mathew; Manuel, Atulya; Mallikarjuna Rao, Chamallamudi; Udupa, Nayanabhirama; Rao, Josyula Venkata; Joy, Ann Mary; Gandhi, Prajay; Radhakrishnan, Ethiraj Kannat

2013-01-01

In the present study, active fractions of the methanolic extract of Xanthium strumarium (XS) showing potent cytotoxicity were determined using microculture tetrazolium (MTT) and sulforhodamine B (SRB) assays in selected cancer cell lines. The active fractions viz., chloroform soluble fraction of root (CEXSR), hexane soluble fraction of leaf (HEXSL), hexane soluble fraction of fruits (HEXSF) and chloroform soluble fraction of fruits (CEXSF) of XS were tested in transplantable animal tumor models for their antitumor potential. Dalton's ascitic lymphoma (DLA) cells were used to induce solid and liquid (ascites) tumor in mice. The tumor bearing animals were treated with active fractions at two dose levels (100 and 200 mg/kg). The antitumor activities of the active fractions in tumor bearing animals were monitored with parameters such as body weight and increase in life-span as well as biochemical and hematological modalities (in the case of liquid tumor). Tumor incidence and tumor volume were the parameters monitored in the case of the solid tumor model. The results were analyzed by one-way ANOVA followed by Tukey's post hoc test. The extracts were found to increase the life-span of tumor bearing animals and restore the altered hematological and biochemical parameters significantly.

Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment

PubMed Central

Irimia, Andrei; Goh, S.-Y. Matthew; Torgerson, Carinna M.; Stein, Nathan R.; Chambers, Micah C.; Vespa, Paul M.; Van Horn, John D.

2013-01-01

Objective To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Methods Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. Results We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Conclusion Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. PMID:24011495

Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment.

PubMed

Irimia, Andrei; Goh, S-Y Matthew; Torgerson, Carinna M; Stein, Nathan R; Chambers, Micah C; Vespa, Paul M; Van Horn, John D

2013-10-01

To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. Published by Elsevier B.V.

Real-time monitoring prefrontal activities during online video game playing by functional near-infrared spectroscopy.

PubMed

Li, Yue; Zhang, Lei; Long, Kehong; Gong, Hui; Lei, Hao

2018-02-16

A growing body of literature has suggested that video game playing can induce functional and structural plasticity of the brain. The underlying mechanisms, however, remain poorly understood. In this study, functional near-infrared spectroscopy (fNIRS) was used to record prefrontal activities in 24 experienced game players when they played a massively multiplayer online battle arena video game, League of Legends (LOL), under naturalistic conditions. It was observed that game onset was associated with significant activations in the ventrolateral prefrontal cortex (VLPFC) and concomitant deactivations in the dorsolateral prefrontal cortex (DLPFC) and frontal pole area (FPA). Game events, such as slaying an enemy and being slain by an enemy evoked region-specific time-locked hemodynamic/oxygenation responses in the prefrontal cortex (PFC). It was proposed that the VLPFC activities during LOL playing are likely responses to visuo-motor task load of the game, while the DLPFC/FPA activities may be involved in the constant shifts of attentional states and allocation of cognitive resources required by game playing. The present study demonstrated that it is feasible to use fNIRS to monitor real-time prefrontal activity during online video game playing. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reactivation of a Deep Seated Gravitational Slope Deformation observed during the recent seismic events in Central Italy.

NASA Astrophysics Data System (ADS)

Amato, Gabriele; Aringoli, Domenico; Devoti, Roberto; Fubelli, Giandomenico; Galvani, Alessandro; Pambianchi, Gilberto; Sepe, Vincenzo

2017-04-01

Deep-Seated Gravitational Slope Deformations (DSGSDs) represent an important geomorphological feature of the European mountain chains and several cases from Central Apennine (Italy) are accurately described in literature. These phenomena generally present evident geomorphological markers (e.g. double ridges, trenches, counterslopes) and low activity rates (i.e. mm to cm per year), which can be triggered by many different means (e.g. seismic activity, erosional processes, rainfall, post-glacial debuttressing). To understand which is the most influential factor in DSGSDs' activity is rarely an easy task because this can vary from case to case. This work illustrates the outcomes provided by a monitoring activity conducted along the Mt. Frascare slope (Fiastra Lake, Marche region, Italy). The monitoring system is composed by 4 low cost GPS stations, based on single-frequency receivers, and 2 double-frequency GPS stations, aimed to cross-check the surface deformations measured by the two types of monitoring stations. The 6 GPS stations have been operated in place starting from October 2014 grounded on the base of a geomorphological field survey of the investigated phenomenon. Two stations have been equipped with both receiver types in order to facilitate the comparison of the results. The Fiastra DSGSD affects a marly limestone bedrock throughout a >5km2 area and along a slope against which a dam for hydroelectric power leans. Our monitoring system allowed to measure the Fiastra DSGSD's seismically induced relative displacements on the order of two mean steps of about 10 cm, due to the recent seismic sequence occurred in Central Italy in 2016, which resulted considerably higher than the observed mean annual velocity (≈5mm/y).

Peptide YY induces characteristic meal patterns of aged mice.

PubMed

Mogami, Sachiko; Yamada, Chihiro; Fujitsuka, Naoki; Hattori, Tomohisa

2017-11-01

Changes in eating behavior occur in the elderly due to oral and swallowing dysfunctions. We aimed to clarify the difference between basal meal patterns of young and aged mice in relation to appetite regulating hormones. Thirty two of young (7-week-old) and aged (23-25-month-old) C57BL/6 male mice were acclimated to a single housing and then transferred to a highly sensitive automated feeding monitoring device. Feeding behavior was monitored from the onset of the dark phase after habituation to the device. Plasma peptide YY (PYY) levels were assessed under the several feeding status or after treatment of PYY. PYY and its receptor (NPY Y2 receptor, Y2R) antagonist were intraperitoneally administered 30min before the monitoring. Although the basal 24-h meal amounts did not differ by age, the total meal time and frequency of minimum feeding activity (bout) were significantly increased and the average bout size and time per bout were significantly decreased in aged mice. PYY dynamics were abnormal and the temporal reduction in food intake by exogenous PYY was more prominent in aged mice than in young mice. PYY administration to young mice induced aged-like meal patterns, and Y2R antagonist administration to aged mice induced young-like meal patterns. Aged mice exhibited characteristic meal patterns probably due to PYY metabolism dysfunction and/or enhanced PYY-Y2R signaling, suggesting a novel method for assessing eating difficulties in aged animals and a potential target for the remedy. Copyright © 2017 Elsevier Inc. All rights reserved.

Hydrogen Gas Inhalation Attenuates Seawater Instillation-Induced Acute Lung Injury via the Nrf2 Pathway in Rabbits.

PubMed

Diao, Mengyuan; Zhang, Sheng; Wu, Lifeng; Huan, Le; Huang, Fenglou; Cui, Yunliang; Lin, Zhaofen

2016-12-01

Seawater instillation-induced acute lung injury involves oxidative stress and apoptosis. Although hydrogen gas inhalation is reportedly protective in multiple types of lung injury, the effect of hydrogen gas inhalation on seawater instillation-induced acute lung injury remains unknown. This study investigated the effect of hydrogen gas on seawater instillation-induced acute lung injury and explored the mechanisms involved. Rabbits were randomly assigned to control, hydrogen (2 % hydrogen gas inhalation), seawater (3 mL/kg seawater instillation), and seawater + hydrogen (3 mL/kg seawater instillation + 2 % hydrogen gas inhalation) groups. Arterial partial oxygen pressure and lung wet/dry weight ratio were detected. Protein content in bronchoalveolar lavage fluid (BALF) and serum as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were determined. Hematoxylin-eosin staining was used to monitor changes in lung specimens, and malondialdehyde (MDA) content and myeloperoxidase (MPO) activity were assayed. In addition, NF-E2-related factor (Nrf) 2 and heme oxygenase (HO)-1 mRNA and protein expression were measured, and apoptosis was assessed by measuring caspase-3 expression and using terminal deoxy-nucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. Hydrogen gas inhalation markedly improved lung endothelial permeability and decreased both MDA content and MPO activity in lung tissue; these changes were associated with decreases in TNF-α, IL-1β, and IL-6 in BALF. Hydrogen gas also alleviated histopathological changes and cell apoptosis. Moreover, Nrf2 and HO-1 expressions were significantly activated and caspase-3 expression was inhibited. These results demonstrate that hydrogen gas inhalation attenuates seawater instillation-induced acute lung injury in rabbits and that the protective effects observed may be related to the activation of the Nrf2 pathway.

Shale Gas Exploration and Exploitation Induced Risks - SHEER

NASA Astrophysics Data System (ADS)

Capuano, Paolo; Orlecka-Sikora, Beata; Lasocki, Stanislaw; Cesca, Simone; Gunning, Andrew; jaroslawsky, Janusz; Garcia-Aristizabal, Alexander; Westwood, Rachel; Gasparini, Paolo

2017-04-01

Shale gas operations may affect the quality of air, water and landscapes; furthermore, it can induce seismic activity, with the possible impacts on the surrounding infrastructure. The SHEER project aims at setting up a probabilistic methodology to assess and mitigate the short and the long term environmental risks connected to the exploration and exploitation of shale gas. In particular we are investigating risks associated with groundwater contamination, air pollution and induced seismicity. A shale gas test site located in Poland (Wysin) has been monitored before, during and after the fracking operations with the aim of assessing environmental risks connected with groundwater contamination, air pollution and earthquakes induced by fracking and injection of waste water. The severity of each of these hazards depends strongly on the unexpected enhanced permeability pattern, which may develop as an unwanted by-product of the fracking processes and may become pathway for gas and fluid migration towards underground water reservoirs or the surface. The project is devoted to monitor and understand how far this enhanced permeability pattern develops both in space and time. The considered hazards may be at least partially inter-related as they all depend on this enhanced permeability pattern. Therefore they are being approached from a multi-hazard, multi parameter perspective. We expect to develop methodologies and procedures to track and model fracture evolution around shale gas exploitation sites and a robust statistically based, multi-parameter methodology to assess environmental impacts and risks across the operational lifecycle of shale gas. The developed methodologies are going to be applied and tested on a comprehensive database consisting of seismicity, changes of the quality of ground-waters and air, ground deformations, and operational data collected from the ongoing monitoring episode (Wysin) and past episodes: Lubocino (Poland), Preese Hall (UK), Oklahoma (USA), Groningen Field (Netherlands), Gross Schönebeck (Germany), The Geysers (USA), Cooper Basin(Australia). Best practices to be applied in Europe to monitor and minimize any environmental impacts will be worked out with the involvement of governmental decisional bodies, private industries and experts This work was supported under SHEER: "Shale Gas Exploration and Exploitation Induced Risks" project n.640896, funded from Horizon 2020 - R&I Framework Programme, call H2020-LCE-2014-1

Delayed luminescence to monitor programmed cell death induced by berberine on thyroid cancer cells

NASA Astrophysics Data System (ADS)

Scordino, Agata; Campisi, Agata; Grasso, Rosaria; Bonfanti, Roberta; Gulino, Marisa; Iauk, Liliana; Parenti, Rosalba; Musumeci, Francesco

2014-11-01

Correlation between apoptosis and UVA-induced ultraweak photon emission delayed luminescence (DL) from tumor thyroid cell lines was investigated. In particular, the effects of berberine, an alkaloid that has been reported to have anticancer activities, on two cancer cell lines were studied. The FTC-133 and 8305C cell lines, as representative of follicular and anaplastic thyroid human cancer, respectively, were chosen. The results show that berberine is able to arrest cell cycle and activate apoptotic pathway as shown in both cell lines by deoxyribonucleic acid fragmentation, caspase-3 cleavage, p53 and p27 protein overexpression. In parallel, changes in DL spectral components after berberine treatment support the hypothesis that DL from human cells originates mainly from mitochondria, since berberine acts especially at the mitochondrial level. The decrease of DL blue component for both cell lines could be related to the decrease of intra-mitochondrial nicotinamide adenine dinucleotide and may be a hallmark of induced apoptosis. In contrast, the response in the red spectral range is different for the two cell lines and may be ascribed to a different iron homeostasis.

Stimulation of complement component C3 synthesis in macrophagelike cell lines by group B streptococci.

PubMed Central

Goodrum, K J

1987-01-01

Complement levels and complement activation are key determinants in streptococcus-induced inflammatory responses. Activation of macrophage functions, such as complement synthesis, by group B streptococci (GBS) was examined as a possible component of GBS-induced chronic inflammation. Using an enzyme-linked immunosorbent assay, secreted C3 from mouse macrophagelike cell lines (PU5-1.8 and J774A.1) was monitored after cultivation with GBS. Whole, heat-killed GBS (1 to 10 CFU per macrophage) of both type Ia and III strains induced 25 to 300% increases in secreted C3 in both cell lines after a 24-h cultivation. GBS-treated cell lines exhibited increases in secreted lysozyme (10%) and in cellular protein (25 to 50%). Inhibition of macrophage phagocytosis by cytochalasin B inhibited GBS stimulation of C3. Purified cell walls of GBS type III strain 603-79 (1 to 10 micrograms/ml) also enhanced C3 synthesis. Local enhancement of macrophage C3 production by ingested streptococci or by persistent cell wall antigens may serve to promote chronic inflammatory responses. PMID:3552987

Physiological changes induced in four bacterial strains following oxidative stress.

PubMed

Baatout, S; De Boever, P; Mergeay, M

2006-01-01

In order to study the behaviour and resistance of bacteria under extreme conditions, physiological changes associated with oxidative stress were monitored using flow cytometry. The study was conducted to assess the maintenance of membrane integrity and potential as well as the esterase activity, the intracellular pH and the production of superoxide anions in four bacterial strains (Ralstonia metallidurans, Escherichia coli, Shewanella oneidensis and Deinococcus radiodurans). The strains were chosen for their potential usefulness in bioremediation. Suspensions of R. metallidurans, E. coli, S. oneidensis and D. radiodurans were submitted to 1 h oxidative stress (H2O2 at various concentrations from 0 to 880 mM). Cell membrane permeability (propidium iodide) and potential (rhodamine-123, 3,3'-dihexyloxacarbocyanine iodide), intracellular esterase activity (fluorescein diacetate), intracellular reactive oxygen species concentration (hydroethidine) and intracellular pH (carboxyflurorescein diacetate succinimidyl ester (5(6)) were monitored to evaluate the physiological state and the overall fitness of individual bacterial cells under oxidative stress. The four bacterial strains exhibited varying sensitivities towards H2O2. However, for all bacterial strains, some physiological damage could already be observed from 13.25 mM H2O2 onwards, in particular with regard to their membrane permeability. Depending on the bacterial strains, moderate to high physiological damage could be observed between 13.25 mM and 220 mM H2O2. Membrane potential, esterase activity, intracellular pH and production of superoxide anion production were considerably modified at high H2O2 concentrations in all four strains. In conclusion, we show that a range of significant physiological alterations occurs when bacteria are challenged with H2O2 and fluorescent staining methods coupled with flow cytometry are useful for monitoring the changes induced not only by oxidative stress but also by other stresses like temperature, radiation, pressure, pH, etc....

Monitoring skin microvascular dysfunction of type 1 diabetic mice using in vivo skin optical clearing

NASA Astrophysics Data System (ADS)

Feng, Wei; Shi, Rui; Zhu, Dan

2018-02-01

To monitor skin microvascular dysfunction of alloxan-induced type 1 diabetic mice model. In this work, we used laser speckle contrast imaging and hyperspectral imaging through in vivo skin optical clearing method to simultaneously monitor the noradrenaline-induced response of microvascular blood flow and blood oxygen with the development of diabetes. The main results showed that venous and arterious blood flow steadily decreased without recovery after injecting noradrenaline (NE), furthermore the influence of NE-induced arterious blood oxygen response greatly decreased, especially for 2-weeks and 4-weeks diabetic mice. This study demonstrated that skin microvascular function was a potential research biomarker for early warning in the occurrence and development of diabetes. And it provides a feasible solution to realize visualization of cutaneous microvessels for monitoring microvascular reactivity.

Stress-Induced Fracturing of Reservoir Rocks: Acoustic Monitoring and μCT Image Analysis

NASA Astrophysics Data System (ADS)

Pradhan, Srutarshi; Stroisz, Anna M.; Fjær, Erling; Stenebråten, Jørn F.; Lund, Hans K.; Sønstebø, Eyvind F.

2015-11-01

Stress-induced fracturing in reservoir rocks is an important issue for the petroleum industry. While productivity can be enhanced by a controlled fracturing operation, it can trigger borehole instability problems by reactivating existing fractures/faults in a reservoir. However, safe fracturing can improve the quality of operations during CO2 storage, geothermal installation and gas production at and from the reservoir rocks. Therefore, understanding the fracturing behavior of different types of reservoir rocks is a basic need for planning field operations toward these activities. In our study, stress-induced fracturing of rock samples has been monitored by acoustic emission (AE) and post-experiment computer tomography (CT) scans. We have used hollow cylinder cores of sandstones and chalks, which are representatives of reservoir rocks. The fracture-triggering stress has been measured for different rocks and compared with theoretical estimates. The population of AE events shows the location of main fracture arms which is in a good agreement with post-test CT image analysis, and the fracture patterns inside the samples are visualized through 3D image reconstructions. The amplitudes and energies of acoustic events clearly indicate initiation and propagation of the main fractures. Time evolution of the radial strain measured in the fracturing tests will later be compared to model predictions of fracture size.

Influence of experimental oesophageal acidification on masseter muscle activity, cervicofacial behaviour and autonomic nervous activity in wakefulness.

PubMed

Ohmure, H; Sakoguchi, Y; Nagayama, K; Numata, M; Tsubouchi, H; Miyawaki, S

2014-06-01

Recent studies have been revealing the relationship between the stomatognathic system and the gastrointestinal tract. However, the effect of oesophageal acid stimulation on masticatory muscle activity during wakefulness has not been fully elucidated. To examine whether intra-oesophageal acidification induces masticatory muscle activity, a randomised trial was conducted investigating the effect of oesophageal acid infusion on masseter muscle activity, autonomic nervous system (ANS) activity and subjective symptoms. Polygraphic monitoring consisting of electromyography of the masseter muscle, electrocardiography and audio-video recording was performed in 15 healthy adult men, using three different 30-min interventions: (i) no infusion, (ii) intra-oesophageal saline infusion and (iii) intra-oesophageal infusion of acidic solution (0·1 N HCl; pH 1·2). This study was registered with the UMIN Clinical Trials Registry, UMIN000005350. Oesophageal acid stimulation significantly increased masseter muscle activity during wakefulness, especially when no behaviour was performed in the oro-facial region. Chest discomfort, including heartburn, also increased significantly after oesophageal acid stimulation; however, no significant correlation was observed between increased subjective symptoms and masseter muscle activity. Oesophageal acid infusion also altered ANS activity; a significant correlation was observed between masticatory muscle changes and parasympathetic nervous system activity. These findings suggest that oesophageal-derived ANS modulation induces masseter muscle activity, irrespective of the presence or absence of subjective gastrointestinal symptoms. © 2014 John Wiley & Sons Ltd.

Amiodarone-induced hypothyroidism. A common complication of prolonged therapy: a report of eight cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hawthorne, G.C.; Campbell, N.P.; Geddes, J.S.

1985-06-01

Amiodarone is a widely used antiarrhythmic drug, which contains 75 mg of iodide per 200 mg of active substance. Eight patients receiving long-term amiodarone therapy became hypothyroid. Seven of these patients had no previous history of thyroid dysfunction or goiter. Antithyroid antibodies were absent, and standard perchlorate discharge tests were positive in seven patients when hypothyroidism was diagnosed. In one patient, amiodarone therapy was withdrawn; over the next nine months, the hypothyroidism resolved, and results of the perchlorate discharge test reverted to normal. The authors conclude that amiodarone-induced hypothyroidism is similar to previously described iodide-induced hypothyroidism. It may develop inmore » the absence of a previous history of thyroid disease, and all patients receiving long-term amiodarone therapy should therefore be regularly monitored for hypothyroidism.« less

Agonist-induced conformational changes in the G-protein-coupling domain of the β2 adrenergic receptor

PubMed Central

Ghanouni, Pejman; Steenhuis, Jacqueline J.; Farrens, David L.; Kobilka, Brian K.

2001-01-01

The majority of extracellular physiologic signaling molecules act by stimulating GTP-binding protein (G-protein)-coupled receptors (GPCRs). To monitor directly the formation of the active state of a prototypical GPCR, we devised a method to site specifically attach fluorescein to an endogenous cysteine (Cys-265) at the cytoplasmic end of transmembrane 6 (TM6) of the β2 adrenergic receptor (β2AR), adjacent to the G-protein-coupling domain. We demonstrate that this tag reports agonist-induced conformational changes in the receptor, with agonists causing a decline in the fluorescence intensity of fluorescein-β2AR that is proportional to the biological efficacy of the agonist. We also find that agonists alter the interaction between the fluorescein at Cys-265 and fluorescence-quenching reagents localized to different molecular environments of the receptor. These observations are consistent with a rotation and/or tilting of TM6 on agonist activation. Our studies, when compared with studies of activation in rhodopsin, indicate a general mechanism for GPCR activation; however, a notable difference is the relatively slow kinetics of the conformational changes in the β2AR, which may reflect the different energetics of activation by diffusible ligands. PMID:11353823

Rac1 and Cdc42 GTPases regulate shear stress-driven β-catenin signaling in osteoblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan, Qiaoqiao; Cho, Eunhye; Yokota, Hiroki

2013-04-19

Highlights: •Shear stress increased TCF/LEF activity and stimulated β-catenin nuclear localization. •Rac1, Cdc42, and RhoA displayed distinct dynamic activity patterns under flow. •Rac1 and Cdc42, but not RhoA, regulate shear stress-driven TCF/LEF activation. •Cytoskeleton did not significantly affect shear stress-induced TCF/LEF activation. -- Abstract: Beta-catenin-dependent TCF/LEF (T-cell factor/lymphocyte enhancing factor) is known to be mechanosensitive and an important regulator for promoting bone formation. However, the functional connection between TCF/LEF activity and Rho family GTPases is not well understood in osteoblasts. Herein we investigated the molecular mechanisms underlying oscillatory shear stress-induced TCF/LEF activity in MC3T3-E1 osteoblast cells using live cell imaging.more » We employed fluorescence resonance energy transfer (FRET)-based and green fluorescent protein (GFP)-based biosensors, which allowed us to monitor signal transduction in living cells in real time. Oscillatory (1 Hz) shear stress (10 dynes/cm{sup 2}) increased TCF/LEF activity and stimulated translocation of β-catenin to the nucleus with the distinct activity patterns of Rac1 and Cdc42. The shear stress-induced TCF/LEF activity was blocked by the inhibition of Rac1 and Cdc42 with their dominant negative mutants or selective drugs, but not by a dominant negative mutant of RhoA. In contrast, constitutively active Rac1 and Cdc42 mutants caused a significant enhancement of TCF/LEF activity. Moreover, activation of Rac1 and Cdc42 increased the basal level of TCF/LEF activity, while their inhibition decreased the basal level. Interestingly, disruption of cytoskeletal structures or inhibition of myosin activity did not significantly affect shear stress-induced TCF/LEF activity. Although Rac1 is reported to be involved in β-catenin in cancer cells, the involvement of Cdc42 in β-catenin signaling in osteoblasts has not been identified. Our findings in this study demonstrate that both Rac1 and Cdc42 GTPases are critical regulators in shear stress-driven β-catenin signaling in osteoblasts.« less

What Is Being Done to Control Motion Sickness?

NASA Technical Reports Server (NTRS)

Hall, Y. D.

1985-01-01

AFT (Autogenic Feedback Training) involves practicing a series of mental exercises to speed up or slow down the control of autonomic activity. This produces a reduced tendency for autonomic activity levels to diverge from baseline (at rest) under stressful motion-sickness-inducing conditions. Subjects conditions. Subjects engaged in applying AFT exercises are required to closely monitor their own bodily sensations during motion-sickness-eliciting tests. These tests include the Coriolis Sickness Susceptibility Index (CSSI), which consists of sitting a subject into a rotating chair that moves at various speeds while a visual background turns at differing speeds and directions, and the Vertical Acceleration Rotation Device (VARD) test, which involves the placing of a subject in a drum that moves in an upward and downward motion until he or she is sick, while simultaneously monitoring the subject's vital signs. These tests provide investigators with evidence of slight changes in autonomic activities such as increases in heart rate, skin temperature, and sweat. All of these symptoms occur in subjects that experience bodily weakness or discomfort with the onset of motion sickness.

Yeast cell metabolism investigated by CO{_2} production and soft X-ray irradiation

NASA Astrophysics Data System (ADS)

Masini, A.; Batani, D.; Previdi, F.; Milani, M.; Pozzi, A.; Turcu, E.; Huntington, S.; Takeyasu, H.

1999-01-01

Results obtained using a new technique for studying cell metabolism are presented. The technique, consisting in CO2 production monitoring, has been applied to Saccharomyces cerevisiae yeast cells. Also the cells were irradiated using the soft X-ray laser-plasma source at Rutherford Appleton Laboratory with the aim of producing a damage of metabolic processes at the wall level, responsible for fermentation, without great interference with respiration, taking place in mitochondria, and DNA activity. The source was calibrated with PIN diodes and X-ray spectrometers and used Teflon stripes as target, emitting X-rays at about 0.9 keV, with a very low penetration in biological material. X-ray doses delivered to the different cell compartments were calculated following a Lambert-Bouguet-Beer law. Immediately after irradiation, the damage to metabolic activity was measured again by monitoring CO2 production. Results showed a general reduction in gas production by irradiated samples, together with non-linear and non-monotone response to dose. There was also evidence of oscillations in cell metabolic activity and of X-ray induced changes in oscillation frequency.

Gold nanoparticle-assisted all optical localized stimulation and monitoring of Ca2+ signaling in neurons

PubMed Central

Lavoie-Cardinal, Flavie; Salesse, Charleen; Bergeron, Éric; Meunier, Michel; De Koninck, Paul

2016-01-01

Light-assisted manipulation of cells to control membrane activity or intracellular signaling has become a major avenue in life sciences. However, the ability to perform subcellular light stimulation to investigate localized signaling has been limited. Here, we introduce an all optical method for the stimulation and the monitoring of localized Ca2+ signaling in neurons that takes advantage of plasmonic excitation of gold nanoparticles (AuNPs). We show with confocal microscopy that 800 nm laser pulse application onto a neuron decorated with a few AuNPs triggers a transient increase in free Ca2+, measured optically with GCaMP6s. We show that action potentials, measured electrophysiologically, can be induced with this approach. We demonstrate activation of local Ca2+ transients and Ca2+ signaling via CaMKII in dendritic domains, by illuminating a single or few functionalized AuNPs specifically targeting genetically-modified neurons. This NP-Assisted Localized Optical Stimulation (NALOS) provides a new complement to light-dependent methods for controlling neuronal activity and cell signaling. PMID:26857748

Potassium sensing histidine kinase in Bacillus subtilis.

PubMed

López, Daniel; Gontang, Erin A; Kolter, Roberto

2010-01-01

The soil-dwelling organism Bacillus subtilis is able to form multicellular aggregates known as biofilms. It was recently reported that the process of biofilm formation is activated in response to the presence of various, structurally diverse small-molecule natural products. All of these small-molecule natural products made pores in the membrane of the bacterium, causing the leakage of potassium cations from the cytoplasm of the cell. The potassium cation leakage was sensed by the membrane histidine kinase KinC, triggering the genetic pathway to the production of the extracellular matrix that holds cells within the biofilm. This chapter presents the methodology used to characterize the leakage of cytoplasmic potassium as the signal that induces biofilm formation in B. subtilis via activation of KinC. Development of novel techniques to monitor activation of gene expression in microbial populations led us to discover the differentiation of a subpopulation of cells specialized to produce the matrix that holds all cells together within the biofilm. This phenomenon of cell differentiation was previously missed by conventional techniques used to monitor transcriptional gene expression. Copyright © 2010 Elsevier Inc. All rights reserved.

Observation of ground deformation associated with hydraulic fracturing and seismicity in the Western Canadian Sedimentary Basin

NASA Astrophysics Data System (ADS)

Kubanek, J.; Liu, Y.; Harrington, R. M.; Samsonov, S.

2017-12-01

In North America, the number of induced earthquakes related to fluid injection due to the unconventional recovery of oil and gas resources has increased significantly within the last five years. Recent studies demonstrate that InSAR is an effective tool to study surface deformation due to large-scale wastewater injection, and highlight the value of surface deformation monitoring with respect to understanding evolution of pore pressure and stress at depth - vital parameters to forecast fault reactivation, and thus, induced earthquakes. In contrast to earthquakes related to the injection of large amounts of wastewater, seismic activity related to the hydraulic fracturing procedure itself was, until recently, considered to play a minor role without significant hazard. In the Western Canadian Sedimentary Basin (WCSB), however, Mw>4 earthquakes have recently led to temporary shutdown of industrial injection activity, causing multi-million dollar losses to operators and raising safety concerns with the local population. Recent studies successfully utilize seismic data and modeling to link seismic activity with hydraulic fracturing in the WCSB. Although the study of surface deformation is likely the most promising tool for monitoring integrity of a well and to derive potential signatures prior to moderate or large induced events, InSAR has, to date, not been utilized to detect surface deformation related to hydraulic fracturing and seismicity. We therefore plan to analyze time-series of SAR data acquired between 1991 to present over two target sites in the WCSB that will enable the study of long- and short-term deformation. Since the conditions for InSAR are expected to be challenging due to spatial and temporal decorrelation, we have designed corner reflectors that will be installed at one target site to improve interferometric performance. The corner reflectors will be collocated with broadband seismometers and Trimble SeismoGeodetic Systems that simultaneously measure GNSS positioning and acceleration. We expect the joint data analysis of dense seismic and geodetic observations to give new insights about the correlation between surface deformation, fluid injection, and induced seismicity that can be used to assess the hazard potential of hydraulic fracturing in the WCSB.

Geophysical Monitoring of Coupled Microbial and Geochemical Processes During Stimulated Subsurface Bioremediation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Kenneth H.; Kemna, Andreas; Wilkins, Michael J.

2009-08-05

Understanding how microorganisms alter their physical and chemical environment during bioremediation is hindered by our inability to resolve subsurface microbial activity with high spatial resolution. Here we demonstrate the use of a minimally invasive geophysical technique to monitor stimulated microbial activity during acetate amendment in an aquifer near Rifle, Colorado. During electrical induced polarization (IP) measurements, spatiotemporal variations in the phase response between imposed electric current and the resultant electric field correlated with changes in groundwater geochemistry accompanying stimulated iron and sulfate reduction and sulfide mineral precipitation. The magnitude of the phase response varied with measurement frequency (0.125 and 1more » Hz) andwasdependent upon the dominant metabolic process. The spectral effect was corroborated using a biostimulated column experiment containing Rifle sediments and groundwater. Fluids and sediments recovered from regions exhibiting an anomalous phase response were enriched in Fe(II), dissolved sulfide, and cell-associated FeS nanoparticles. The accumulation of mineral precipitates and electroactive ions altered the ability of pore fluids to conduct electrical charge, accounting for the anomalous IP response and revealing the usefulness of multifrequency IP measurements for monitoring mineralogical and geochemical changes accompanying stimulated subsurface bioremediation.« less

Dual-Color Monitoring Overcomes the Limitations of Single Bioluminescent Reporters in Fast-Growing Microbes and Reveals Phase-Dependent Protein Productivity during the Metabolic Rhythms of Saccharomyces cerevisiae

PubMed Central

Krishnamoorthy, Archana

2015-01-01

Luciferase is a useful, noninvasive reporter of gene regulation that can be continuously monitored over long periods of time; however, its use is problematic in fast-growing microbes like bacteria and yeast because rapidly changing cell numbers and metabolic states also influence bioluminescence, thereby confounding the reporter's signal. Here we show that these problems can be overcome in the budding yeast Saccharomyces cerevisiae by simultaneously monitoring bioluminescence from two different colors of beetle luciferase, where one color (green) reports activity of a gene of interest, while a second color (red) is stably expressed and used to continuously normalize green bioluminescence for fluctuations in signal intensity that are unrelated to gene regulation. We use this dual-luciferase strategy in conjunction with a light-inducible promoter system to test whether different phases of yeast respiratory oscillations are more suitable for heterologous protein production than others. By using pulses of light to activate production of a green luciferase while normalizing signal variation to a red luciferase, we show that the early reductive phase of the yeast metabolic cycle produces more luciferase than other phases. PMID:26162874

Time-Lapse Monitoring with 4D Seismic Coda Waves in Active, Passive and Ambient Noise Data

NASA Astrophysics Data System (ADS)

Lumley, D. E.; Kamei, R.; Saygin, E.; Shragge, J. C.

2017-12-01

The Earth's subsurface is continuously changing, due to temporal variations in fluid flow, stress, temperature, geomechanics and geochemistry, for example. These physical changes occur at broad tectonic and earthquake scales, and also at very detailed near-surface and reservoir scales. Changes in the physical states of the earth cause time-varying changes in the physical properties of rocks and fluids, which can be monitored with natural or manmade seismic waves. Time-lapse (4D) seismic monitoring is important for applications related to natural and induced seismicity, hydrocarbon and groundwater reservoir depletion, CO2 sequestration etc. An exciting new research area involves moving beyond traditional methods in order to use the full complex time-lapse scattered wavefield (4D coda waves) for both manmade active-source 3D/4D seismic data, and also to use continuous recordings of natural-source passive seismic data, especially (micro) earthquakes and ocean ambient noise. This research involves full wave-equation approaches including waveform inversion (FWI), interferometry, Large N sensor arrays, "big data" information theory, and high performance supercomputing (HPC). I will present high-level concepts and recent data results that are quite spectacular and highly encouraging.

Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis.

PubMed

Ye, Deju; Shuhendler, Adam J; Pandit, Prachi; Brewer, Kimberly D; Tee, Sui Seng; Cui, Lina; Tikhomirov, Grigory; Rutt, Brian; Rao, Jianghong

2014-10-01

Non-invasive detection of caspase-3/7 activity in vivo has provided invaluable predictive information regarding tumor therapeutic efficacy and anti-tumor drug selection. Although a number of caspase-3/7 targeted fluorescence and positron emission tomography (PET) imaging probes have been developed, there is still a lack of gadolinium (Gd)-based magnetic resonance imaging (MRI) probes that enable high spatial resolution detection of caspase-3/7 activity in vivo . Here we employ a self-assembly approach and develop a caspase-3/7 activatable Gd-based MRI probe for monitoring tumor apoptosis in mice. Upon reduction and caspase-3/7 activation, the caspase-sensitive nano-aggregation MR probe (C-SNAM: 1 ) undergoes biocompatible intramolecular cyclization and subsequent self-assembly into Gd-nanoparticles (GdNPs). This results in enhanced r 1 relaxivity-19.0 (post-activation) vs. 10.2 mM -1 s -1 (pre-activation) at 1 T in solution-and prolonged accumulation in chemotherapy-induced apoptotic cells and tumors that express active caspase-3/7. We demonstrate that C-SNAM reports caspase-3/7 activity by generating a significantly brighter T 1 -weighted MR signal compared to non-treated tumors following intravenous administration of C-SNAM, providing great potential for high-resolution imaging of tumor apoptosis in vivo .

Impact of Procyanidins from Different Berries on Caspase 8 Activation in Colon Cancer

PubMed Central

Minker, Carole; Duban, Livine; Karas, Daniel; Järvinen, Päivi; Lobstein, Annelise; Muller, Christian D.

2015-01-01

Scope. The aim of this work is to identify which proapoptotic pathway is induced in human colon cancer cell lines, in contact with proanthocyanidins extracted from various berries. Methods and Results. Proanthocyanidins (Pcys) extracted from 11 berry species are monitored for proapoptotic activities on two related human colon cancer cell lines: SW480-TRAIL-sensitive and SW620-TRAIL-resistant. Apoptosis induction is monitored by cell surface phosphatidylserine (PS) detection. Lowbush blueberry extract triggers the strongest activity. When tested on the human monocytic cell line THP-1, blueberry Pcys are less effective for PS externalisation and DNA fragmentation is absent, highlighting a specificity of apoptosis induction in gut cells. In Pcys-treated gut cell lines, caspase 8 (apoptosis extrinsic pathway) but not caspase 9 (apoptosis intrinsic pathway) is activated after 3 hours through P38 phosphorylation (90 min), emphasizing the potency of lowbush blueberry Pcys to eradicate gut TRAIL-resistant cancer cells. Conclusion. We highlight here that berries Pcys, especially lowbush blueberry Pcys, are of putative interest for nutritional chemoprevention of colorectal cancer in view of their apoptosis induction in a human colorectal cancer cell lines. PMID:26180579

Serotonin transporter genotype and action monitoring dysfunction: a possible substrate underlying increased vulnerability to depression.

PubMed

Holmes, Avram J; Bogdan, Ryan; Pizzagalli, Diego A

2010-04-01

A variable number of tandem repeats (short (S) vs long (L)) in the promoter region of the serotonin transporter gene (5-HTTLPR) and a functional variant of a single-nucleotide polymorphism (rs25531) in 5-HTTLPR have been recently associated with increased risk for major depressive disorder (MDD). In particular, relative to L/L or L(A) homozygotes (hereafter referred to as L' participants), S carriers or L(g)-allele carriers (S' participants) have been found to have a higher probability of developing depression after stressful life events, although inconsistencies abound. Previous research indicates that patients with MDD are characterized by executive dysfunction and abnormal activation within the anterior cingulate cortex (ACC), particularly in situations requiring adaptive behavioral adjustments following errors and response conflict (action monitoring). The goal of this study was to test whether psychiatrically healthy S' participants would show abnormalities similar to those of MDD subjects. To this end, 19 S' and 14 L' participants performed a modified Flanker task known to induce errors, response conflict, and activations in various ACC subdivisions during functional magnetic resonance imaging. As hypothesized, relative to L' participants, S' participants showed (1) impaired post-error and post-conflict behavioral adjustments; (2) larger error-related rostral ACC activation; and (3) lower conflict-related dorsal ACC activation. As similar behavioral and neural dysfunctions have been recently described in MDD patient samples, the current results raise the possibility that impaired action monitoring and associated ACC dysregulation may represent risk factors increased vulnerability to depression.

Specific phosphopeptide binding regulates a conformational change in the PI 3-kinase SH2 domain associated with enzyme activation.

PubMed Central

Shoelson, S E; Sivaraja, M; Williams, K P; Hu, P; Schlessinger, J; Weiss, M A

1993-01-01

SH2 (src-homology 2) domains define a newly recognized binding motif that mediates the physical association of target phosphotyrosyl proteins with downstream effector enzymes. An example of such phosphoprotein-effector coupling is provided by the association of phosphatidylinositol 3-kinase (PI 3-kinase) with specific phosphorylation sites within the PDGF receptor, the c-Src/polyoma virus middle T antigen complex and the insulin receptor substrate IRS-1. Notably, phosphoprotein association with the SH2 domains of p85 also stimulates an increase in catalytic activity of the PI 3-kinase p110 subunit, which can be mimicked by phosphopeptides corresponding to targeted phosphoprotein phosphorylation sites. To investigate how phosphoprotein binding to the p85 SH2 domain stimulates p110 catalytic activation, we have examined the differential effects of phosphotyrosine and PDGF receptor-, IRS-1- and c-Src-derived phosphopeptides on the conformation of an isolated SH2 domain of PI 3-kinase. Although phosphotyrosine and both activating and non-activating phosphopeptides bind to the SH2 domain, activating phosphopeptides bind with higher affinity and induce a qualitatively distinct conformational change as monitored by CD and NMR spectroscopy. Amide proton exchange and protease protection assays further show that high affinity, specific phosphopeptide binding induces non-local dynamic SH2 domain stabilization. Based on these findings we propose that specific phosphoprotein binding to the p85 subunit induces a change in SH2 domain structure which is transmitted to the p110 subunit and regulates enzymatic activity by an allosteric mechanism. Images PMID:8382612

Monte Carlo calculations of positron emitter yields in proton radiotherapy.

PubMed

Seravalli, E; Robert, C; Bauer, J; Stichelbaut, F; Kurz, C; Smeets, J; Van Ngoc Ty, C; Schaart, D R; Buvat, I; Parodi, K; Verhaegen, F

2012-03-21

Positron emission tomography (PET) is a promising tool for monitoring the three-dimensional dose distribution in charged particle radiotherapy. PET imaging during or shortly after proton treatment is based on the detection of annihilation photons following the ß(+)-decay of radionuclides resulting from nuclear reactions in the irradiated tissue. Therapy monitoring is achieved by comparing the measured spatial distribution of irradiation-induced ß(+)-activity with the predicted distribution based on the treatment plan. The accuracy of the calculated distribution depends on the correctness of the computational models, implemented in the employed Monte Carlo (MC) codes that describe the interactions of the charged particle beam with matter and the production of radionuclides and secondary particles. However, no well-established theoretical models exist for predicting the nuclear interactions and so phenomenological models are typically used based on parameters derived from experimental data. Unfortunately, the experimental data presently available are insufficient to validate such phenomenological hadronic interaction models. Hence, a comparison among the models used by the different MC packages is desirable. In this work, starting from a common geometry, we compare the performances of MCNPX, GATE and PHITS MC codes in predicting the amount and spatial distribution of proton-induced activity, at therapeutic energies, to the already experimentally validated PET modelling based on the FLUKA MC code. In particular, we show how the amount of ß(+)-emitters produced in tissue-like media depends on the physics model and cross-sectional data used to describe the proton nuclear interactions, thus calling for future experimental campaigns aiming at supporting improvements of MC modelling for clinical application of PET monitoring. © 2012 Institute of Physics and Engineering in Medicine

Space Weather Products and Tools Used in Auroral Monitoring and Forecasting at CCMC/SWRC

NASA Technical Reports Server (NTRS)

Zheng, Yihua; Rastaetter, Lutz

2015-01-01

Key points discussed in this chapter are (1) the importance of aurora research to scientific advances and space weather applications, (2) space weather products at CCMC that are relevant to aurora monitoring and forecasting, and (3) the need for more effort from the whole community to achieve a better and long-lead-time forecast of auroral activity. Aurora, as manifestations of solar wind-magnetosphere-ionosphere coupling that occurs in a region of space that is relatively easy to access for sounding rockets, satellites, and other types of observational platforms, serves as a natural laboratory for studying the underlying physics of the complex system. From a space weather application perspective, auroras can cause surface charging of technological assets passing through the region, result in scintillation effects affecting communication and navigation, and cause radar cluttering that hinders military and civilian applications. Indirectly, an aurora and its currents can induce geomagnetically induced currents (GIC) on the ground, which poses major concerns for the wellbeing and operation of power grids, particularly during periods of intense geomagnetic activity. In addition, accurate auroral forecasting is desired for auroral tourism. In this chapter, we first review some of the existing auroral models and discuss past validation efforts. Such efforts are crucial in transitioning a model(s) from research to operations and for further model improvement and development that also benefits scientific endeavors. Then we will focus on products and tools that are used for auroral monitoring and forecasting at the Space Weather Research Center (SWRC). As part of the CCMC (Community Coordinated Modeling Center), SWRC has been providing space weather services since 2010.

Tropospheric Emissions: Monitoring of Pollution (TEMPO) - Status and Potential Science Studies

NASA Astrophysics Data System (ADS)

Chance, Kelly

2016-05-01

TEMPO is the first NASA Earth Venture Instrument, to launch between 2019 and 2021. It measures atmospheric pollution from Mexico City and Cuba to the Canadian oil sands, and from the Atlantic to the Pacific, hourly at high spatial resolution, ~ 10 km2. It measures the key elements of air pollution chemistry. Geostationary (GEO) measurements capture the variability in the diurnal cycle of emissions and chemistry at sub-urban scale to improve emission inventories, monitor population exposure, and enable emission-control strategies. TEMPO measures the UV/visible spectra to retrieve O3, NO2, SO2, H2 CO, C2 H2 O2, H2 O, aerosols, cloud parameters, and UVB radiation. It tracks aerosol loading. It provides near-real-time air quality products. TEMPO is the North American component of the global geostationary constellation for pollution monitoring, with the European Sentinel-4 and the Korean GEMS. TEMPO studies may include: Solar-induced fluorescence from chlorophyll over land and in the ocean to study tropical dynamics, primary productivity, carbon uptake, to detect red tides, and to study phytoplankton; Measurements of stratospheric intrusions that cause air quality exceedances; Measurements at peaks in vehicle travel to capture the variability in emissions from mobile sources; Measurements of thunderstorm activity, including outflow regions to better quantify lightning NOx and O3 production; Cropland measurements follow the temporal evolution of emissions after fertilizer application and from rain-induced emissions from semi-arid soils; Measurements investigate the chemical processing of primary fire emissions and the secondary formation of VOCs and ozone; Measurements examine ocean halogen emissions and their impact on the oxidizing capacity of coastal environments; Spectra of nighttime lights are markers for human activity, energy conservation, and compliance with outdoor lighting standards intended to reduce light pollution.

A PET Prototype for “In-Beam” Monitoring of Proton Therapy

NASA Astrophysics Data System (ADS)

Vecchio, Sara; Attanasi, Francesca; Belcari, Nicola; Camarda, Manuela; Cirrone, G. A. Pablo; Cuttone, Giacomo; Di Rosa, Francesco; Lanconelli, Nico; Moehrs, Sascha; Rosso, Valeria; Russo, Giorgio; Del Guerra, Alberto

2009-02-01

The in-beam PET is a novel PET application to image the beta+ activity induced in biological tissues by hadronic therapeutic beams. Thanks to the correlation existing between beam-delivered dose profiles and beam-induced activity profiles, in vivo information about the effective ion paths can be extracted from the in-beam pet image. in situ measurements, immediately after patient irradiation, are recommended in order to exploit the maximum statistics, by also detecting the contribution provided by the very short lived isotopes, e.g. 15O. A compact, dedicated tomograph should then be developed for such an application, so as to be used in the treatment room. We developed a small PET prototype in order to demonstrate the feasibility of such a technique for the monitoring of proton therapy of ocular tumors at the CATANA facility (Catania, Italy). The prototype consists of two planar heads with an active area of about 5 cm times 5 cm. Each head is made up of a square position sensitive photomultiplier (Hamamatsu H8500) coupled to a matrix of the same size of LYSO scintillating crystals (2 mm times 2 mm times 18 mm pixel dimensions). Dedicated, compact electronic boards are used for the signal multiplexing, amplification and digitization. The distance between the pair can be varied from 10 cm up to a maximum of about 20 cm. The validation of the prototype was performed on plastic phantoms using 62 MeV protons at the CATANA beam line. Different dose distributions were delivered and a good correlation between the distal fall-off of the activity profiles and of the dose profiles was found, i.e., better than 2 mm along the beam direction.

High Arctic lemmings remain reproductively active under predator-induced elevated stress.

PubMed

Fauteux, Dominique; Gauthier, Gilles; Berteaux, Dominique; Palme, Rupert; Boonstra, Rudy

2018-04-12

Non-consumptive effects of predation have rarely been assessed in wildlife populations even though their impact could be as important as lethal effects. Reproduction of individuals is one of the most important demographic parameters that could be affected by predator-induced stress, which in turn can have important consequences on population dynamics. We studied non-consumptive effects of predation on the reproductive activity (i.e., mating and fertilization) of a cyclic population of brown lemmings exposed to intense summer predation in the Canadian High Arctic. Lemmings were live-trapped, their reproductive activity (i.e., testes visible in males, pregnancy/lactation in females) assessed, and predators were monitored during the summers of 2014 and 2015 within a 9 ha predator-reduction exclosure delimited by a fence and covered by a net, and on an 11 ha control area. Stress levels were quantified non-invasively with fecal corticosterone metabolites (FCM). We found that FCM levels of lemmings captured outside the predator exclosure (n = 50) were 1.6 times higher than inside (n = 51). The proportion of pregnant/lactating adult females did not differ between the two areas, nor did the proportion of adult scrotal males. We found that lemmings showed physiological stress reactions due to high predation risk, but had no sign of reduced mating activity or fertility. Thus, our results do not support the hypothesis of reproductive suppression by predator-induced stress.

ABA-insensitive3, ABA-insensitive5, and DELLAs Interact to activate the expression of SOMNUS and other high-temperature-inducible genes in imbibed seeds in Arabidopsis.

PubMed

Lim, Soohwan; Park, Jeongmoo; Lee, Nayoung; Jeong, Jinkil; Toh, Shigeo; Watanabe, Asuka; Kim, Junghyun; Kang, Hyojin; Kim, Dong Hwan; Kawakami, Naoto; Choi, Giltsu

2013-12-01

Seeds monitor the environment to germinate at the proper time, but different species respond differently to environmental conditions, particularly light and temperature. In Arabidopsis thaliana, light promotes germination but high temperature suppresses germination. We previously reported that light promotes germination by repressing SOMNUS (SOM). Here, we examined whether high temperature also regulates germination through SOM and found that high temperature activates SOM expression. Consistent with this, som mutants germinated more frequently than the wild type at high temperature. The induction of SOM mRNA at high temperature required abscisic acid (ABA) and gibberellic acid biosynthesis, and ABA-insensitive3 (ABI3), ABI5, and DELLAs positively regulated SOM expression. Chromatin immunoprecipitation assays indicated that ABI3, ABI5, and DELLAs all target the SOM promoter. At the protein level, ABI3, ABI5, and DELLAs all interact with each other, suggesting that they form a complex on the SOM promoter to activate SOM expression at high temperature. We found that high-temperature-inducible genes frequently have RY motifs and ABA-responsive elements in their promoters, some of which are targeted by ABI3, ABI5, and DELLAs in vivo. Taken together, our data indicate that ABI3, ABI5, and DELLAs mediate high-temperature signaling to activate the expression of SOM and other high-temperature-inducible genes, thereby inhibiting seed germination.

Anti-inflammatory activities of aqueous extract of Mesona procumbens in experimental mice.

PubMed

Huang, Guan-Jhong; Liao, Jung-Chun; Chiu, Chuan-Sung; Huang, Shyh-Shyun; Lin, Tsung-Hui; Deng, Jeng-Shyan

2012-04-01

Mesona procumbens is consumed as a herbal drink and jelly-type dessert in Taiwan. The aim of this study was to determine the mechanism of anti-inflammatory activities of the aqueous extract of M. procumbens (AMP) using the λ-carrageenin (Carr)-induced mouse paw oedema model. The fingerprint chromatogram of AMP was obtained by high-performance liquid chromatography (HPLC) analysis. To investigate the anti-inflammatory mechanism of AMP, the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in paw oedema were monitored. Serum nitric oxide (NO), tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also evaluated. The fingerprint chromatogram from HPLC indicated that AMP contained protocatechuic acid, chlorogenic acid, vanillic acid and caffeic acid. In the anti-inflammatory test, AMP decreased paw oedema after Carr administration and increased the CAT, SOD and GPx activities and decreased the MDA level in paw oedema at 5 h after Carr injection. AMP also affected the serum NO, TNF-α and IL-1β levels at 5 h after Carr injection. Western blotting revealed that AMP decreased the expression of Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Mesona procumbens has the potential to provide a therapeutic approach to inflammation-associated disorders. Copyright © 2011 Society of Chemical Industry.

Novel direct factor Xa inhibitory compounds from Tenebrio molitor with anti-platelet aggregation activity.

PubMed

Lee, Wonhwa; Kim, Mi-Ae; Park, InWha; Hwang, Jae Sam; Na, MinKyun; Bae, Jong-Sup

2017-11-01

Tenebrio molitor is an edible insect that has antimicrobial, anticancer, and antihypertensive effects. The aim of this study was to identify the unreported bioactive compounds from T. molitor larvae with inhibitory activities against factor Xa (FXa) and platelet aggregation. Isolated compounds were evaluated for their anti-FXa and anti-platelet aggregation properties by monitoring clotting time, platelet aggregation, FXa activity, and thrombus formation. A diketopiperazine (1, cyclo( L -Pro- L -Tyr)) and a phenylethanoid (2, N-acetyltyramine) were isolated and inhibited the catalytic activity of FXa in a mixed inhibition model and inhibited platelet aggregation induced by adenosine diphosphate (ADP) and U46619. They inhibited ADP- and U46619-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) and the expression of P-selectin and PAC-1 in platelets. They also improved the production of nitric oxide and inhibited the oversecretion of endothelin-1 compared to that of the ADP- or U46619-treated group. In an animal model of arterial and pulmonary thrombosis, the isolated compounds showed enhanced antithrombotic effects. They also elicited anticoagulant effects in mice. Compounds 1-2 inhibited ADP-, collagen-, or U46619-induced platelet aggregation and showed similar anti-thrombotic efficacy to rivaroxaban, a positive control. Therefore, 1-2 could serve as candidates and provide scaffolds for the development of new anti-FXa and anti-platelet drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Compound K induced apoptosis via endoplasmic reticulum Ca2+ release through ryanodine receptor in human lung cancer cells.

PubMed

Shin, Dong-Hyun; Leem, Dong-Gyu; Shin, Ji-Sun; Kim, Joo-Il; Kim, Kyung-Tack; Choi, Sang Yoon; Lee, Myung-Hee; Choi, Jung-Hye; Lee, Kyung-Tae

2018-04-01

Extended endoplasmic reticulum (ER) stress may initiate apoptotic pathways in cancer cells, and ER stress has been reported to possibly increase tumor death in cancer therapy. We previously reported that caspase-8 played an important role in compound K-induced apoptosis via activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation in HL-60 human leukemia cells. The mechanisms leading to apoptosis in A549 and SK-MES-1 human lung cancer cells and the role of ER stress have not yet been understood. The apoptotic effects of compound K were analyzed using flow cytometry, and the changes in protein levels were determined using Western blot analysis. The intracellular calcium levels were monitored by staining with Fura-2/AM and Fluo-3/AM. Compound K-induced ER stress was confirmed through increased phosphorylation of eIF2α and protein levels of GRP78/BiP, XBP-1S, and IRE1α in human lung cancer cells. Moreover, compound-K led to the accumulation of intracellular calcium and an increase in m-calpain activities that were both significantly inhibited by pretreatment either with BAPTA-AM (an intracellular Ca 2+ chelator) or dantrolene (an RyR channel antagonist). These results were correlated with the outcome that compound K induced ER stress-related apoptosis through caspase-12, as z-ATAD-fmk (a specific inhibitor of caspase-12) partially ameliorated this effect. Interestingly, 4-PBA (ER stress inhibitor) dramatically improved the compound K-induced apoptosis. Cell survival and intracellular Ca 2+ homeostasis during ER stress in human lung cancer cells are important factors in the induction of the compound K-induced apoptotic pathway.

Pharmacological inhibition of PAR2 with the pepducin P2pal-18S protects mice against acute experimental biliary pancreatitis.

PubMed

Michael, E S; Kuliopulos, A; Covic, L; Steer, M L; Perides, G

2013-03-01

Pancreatic acinar cells express proteinase-activated receptor-2 (PAR2) that is activated by trypsin-like serine proteases and has been shown to exert model-specific effects on the severity of experimental pancreatitis, i.e., PAR2(-/-) mice are protected from experimental acute biliary pancreatitis but develop more severe secretagogue-induced pancreatitis. P2pal-18S is a novel pepducin lipopeptide that targets and inhibits PAR2. In studies monitoring PAR2-stimulated intracellular Ca(2+) concentration changes, we show that P2pal-18S is a full PAR2 inhibitor in acinar cells. Our in vivo studies show that P2pal-18S significantly reduces the severity of experimental biliary pancreatitis induced by retrograde intraductal bile acid infusion, which mimics injury induced by endoscopic retrograde cholangiopancreatography (ERCP). This reduction in pancreatitis severity is observed when the pepducin is given before or 2 h after bile acid infusion but not when it is given 5 h after bile acid infusion. Conversely, P2pal-18S increases the severity of secretagogue-induced pancreatitis. In vitro studies indicate that P2pal-18S protects acinar cells against bile acid-induced injury/death, but it does not alter bile acid-induced intracellular zymogen activation. These studies are the first to report the effects of an effective PAR2 pharmacological inhibitor on pancreatic acinar cells and on the severity of experimental pancreatitis. They raise the possibility that a pepducin such as P2pal-18S might prove useful in the clinical management of patients at risk for developing severe biliary pancreatitis such as occurs following ERCP.

Type 2 Immune Mechanisms in Carbon Nanotube-Induced Lung Fibrosis.

PubMed

Dong, Jie; Ma, Qiang

2018-01-01

T helper (Th) 2-dependent type 2 immune pathways have been recognized as an important driver for the development of fibrosis. Upon stimulation, activated Th2 immune cells and type 2 cytokines interact with inflammatory and tissue repair functions to stimulate an overzealous reparative response to tissue damage, leading to organ fibrosis and destruction. In this connection, type 2 pathways are activated by a variety of insults and pathological conditions to modulate the response. Carbon nanotubes (CNTs) are nanomaterials with a wide range of applications. However, pulmonary exposure to CNTs causes a number of pathologic outcomes in animal lungs, dominated by inflammation and fibrosis. These findings, alongside the rapidly expanding production and commercialization of CNTs and CNT-containing materials in recent years, have raised concerns on the health risk of CNT exposure in humans. The CNT-induced pulmonary fibrotic lesions resemble those of human fibrotic lung diseases, such as idiopathic pulmonary fibrosis and pneumoconiosis, to a certain extent with regard to disease development and pathological features. In fibrotic scenarios, immune cells are activated including varying immune pathways, ranging from innate immune cell activation to autoimmune disease. These events often precede and/or accompany the occurrence of fibrosis. Upon CNT exposure, significant induction and activation of Th2 cells and type 2 cytokines in the lungs are observed. Moreover, type 2 pathways are shown to play important roles in promoting CNT-induced lung fibrosis by producing type 2 pro-fibrotic factors and inducing the reparative phenotypes of macrophages in response to CNTs. In light of the vastly increased demand for nanosafety and the apparent induction and multiple roles of type 2 immune pathways in lung fibrosis, we review the current literature on CNT-induced lung fibrosis, with a focus on the induction and activation of type 2 responses by CNTs and the stimulating function of type 2 signaling on pulmonary fibrosis development. These analyses provide new insights into the mechanistic understanding of CNT-induced lung fibrosis, as well as the potential of using type 2 responses as a monitoring target and therapeutic strategy for human fibrotic lung disease.

Chronic Sleep Fragmentation During the Sleep Period Induces Hypothalamic Endoplasmic Reticulum Stress and PTP1b-Mediated Leptin Resistance in Male Mice

PubMed Central

Hakim, Fahed; Wang, Yang; Carreras, Alba; Hirotsu, Camila; Zhang, Jing; Peris, Eduard; Gozal, David

2015-01-01

Background: Sleep fragmentation (SF) is highly prevalent and may constitute an important contributing factor to excessive weight gain and the metabolic syndrome. Increased endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) leading to the attenuation of leptin receptor signaling in the hypothalamus leads to obesity and metabolic dysfunction. Methods: Mice were exposed to SF and sleep control (SC) for varying periods of time during which ingestive behaviors were monitored. UPR pathways and leptin receptor signaling were assessed in hypothalami. To further examine the mechanistic role of ER stress, changes in leptin receptor (ObR) signaling were also examined in wild-type mice treated with the ER chaperone tauroursodeoxycholic acid (TUDCA), as well as in CHOP −/+ transgenic mice. Results: Fragmented sleep in male mice induced increased food intake starting day 3 and thereafter, which was preceded by increases in ER stress and activation of all three UPR pathways in the hypothalamus. Although ObR expression was unchanged, signal transducer and activator of transcription 3 (STAT3) phosphorylation was decreased, suggesting reduced ObR signaling. Unchanged suppressor of cytokine signaling-3 (SOCS3) expression and increases in protein-tyrosine phosphatase 1B (PTP1B) expression and activity emerged with SF, along with reduced p-STAT3 responses to exogenous leptin. SF-induced effects were reversed following TUDCA treatment and were absent in CHOP −/+ mice. Conclusions: Sleep fragmentation (SF) induces hyperphagic behaviors and reduced leptin signaling in hypothalamus that are mediated by activation of endoplasmic reticulum (ER) stress, and ultimately lead to increased PTP1B activity. ER stress pathways are therefore potentially implicated in SF-induced weight gain and metabolic dysfunction, and may represent a viable therapeutic target. Citation: Hakim F, Wang Y, Carreras A, Hirotsu C, Zhang J, Peris E, Gozal D. Chronic sleep fragmentation during the sleep period induces hypothalamic endoplasmic reticulum stress and ptp1b-mediated leptin resistance in male Mice. SLEEP 2015;38(1):31–40. PMID:25325461

The use of vibration monitoring to record the blasting works impact on buildings surrounding open-pit mines

NASA Astrophysics Data System (ADS)

Sołtys, Anna; Pyra, Józef; Winzer, Jan

2018-04-01

Environmental protection law and geological and mining law require the mineral mining plant to protect its surroundings from the effects of mining operations. This also applies to the negative impact of vibrations induced by blasting works on people and construction facilities. Effective protection is only possible if the level of this impact is known, therefore it is necessary to record it. The thesis formulated in this way has been and continues to be the guiding principle of the research works carried out in the AGH Laboratory of Blasting Work and Environmental Protection. As a result of these works are procedures for conducting preventive activities by open-pit mines in order to minimize the impact of blasting on facilities in the surrounding area. An important element of this activity is the monitoring of vibrations in constructions, which is a source of knowledge for excavation supervisors and engineers performing blasting works, thus contributing to raising the awareness of the responsible operation of the mining plant. Developed in the Laboratory of the Mine's Vibration Monitoring Station (KSMD), after several modernizations, it became a fully automated system for monitoring and recording the impact of blasting works on the surrounding environment. Currently, there are 30 measuring devices in 10 open-pit mines, and additional 8 devices are used to provide periodic measurement and recording services for the mines concerned.

Accuracy, reproducibility and costs of different laboratory assays for the monitoring of unfractionated heparin in clinical practice: a prospective evaluation study and survey among Swiss institutions.

PubMed

Bürki, Susanne; Brand, Béatrice; Escher, Robert; Wuillemin, Walter A; Nagler, Michael

2018-06-09

To investigate the accuracy, reproducibility and costs of different laboratory assays for the monitoring of unfractionated heparin (UFH) in clinical practice and to study test utilisation in Switzerland. Prospective evaluation study and survey among Swiss hospitals and laboratories. Secondary care hospital in rural Switzerland (evaluation study); all Swiss hospitals and laboratories (survey). All consecutive patients, monitored for treatment with UFH during two time periods, were included (May to July 2014 and January to February 2015; n=254). Results of activated partial thromboplastin time (aPTT), thrombin time (TT), prothrombinase-induced clotting time (PiCT) and anti-Xa activity with respect to UFH concentration RESULTS: Spearman's correlation coefficient (r s ) with regard to anti-Xa activity was 0.68 (95% CI 0.60 to 0.75) for aPTT, 0.79 (0.69 to 0.86) for TT and 0.94 (0.93 to 0.95) for PiCT. The correlation (r s ) between anti-Xa activity and heparin concentration as determined by spiking plasma samples was 1.0 (1.0 to 1.0). The coefficient of variation was at most 5% for PiCT and anti-Xa activity (within-run as well as day-to-day variability). The total costs per test in Swiss Francs (SFr) were SFr23.40 for aPTT, SFr33.30 for TT, SFr15.70 for PiCT and SFr24.15 for anti-Xa activity. The various tests were employed in Swiss institutions with the following frequencies: aPTT 53.2%, TT 21.6%, anti-Xa activity 7.2%, PiCT 1.4%; 16.6% of hospitals performed more than one test. The accuracy and reproducibility of PiCT and anti-Xa activity for monitoring of UFH was superior, and analytical costs were equivalent to or lower than aPTT and TT. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Using violet laser-induced chlorophyll fluorescence emission spectra for crop yield assessment of cowpea (Vigna unguiculata (L) Walp) varieties

NASA Astrophysics Data System (ADS)

Anderson, Benjamin; Buah-Bassuah, Paul K.; Tetteh, Jonathan P.

2004-07-01

The use of violet laser-induced chlorophyll fluorescence (LICF) emission spectra to monitor the growth of five varieties of cowpea in the University of Cape Coast Botanical Garden is presented. Radiation from a continuous-wave violet laser diode emitting at 396 nm through a fibre is closely incident on in vivo leaves of cowpea to excite chlorophyll fluorescence, which is detected by an integrated spectrometer with CCD readout. The chlorophyll fluorescence spectra with peaks at 683 and 731 nm were used for growth monitoring of the cowpea plants over three weeks and analysed using Gaussian spectral functions with curve fitted parameters to determine the peak positions, area under the spectral curve and the intensity ratio F683/F731. The variation in the intensity ratio of the chlorophyll bands showed sensitive changes indicating the photosynthetic activity of the cowpea varieties. A discussion of the fluorescence result as compared to conventional assessment is presented with regard to discrimination between the cowpea varieties in terms of crop yield performance.

Fluorescence technique for on-line monitoring of state of hydrogen-producing microorganisms

DOEpatents

Seibert, Michael [Lakewood, CO; Makarova, Valeriya [Golden, CO; Tsygankov, Anatoly A [Pushchino, RU; Rubin, Andrew B [Moscow, RU

2007-06-12

In situ fluorescence method to monitor state of sulfur-deprived algal culture's ability to produce H.sub.2 under sulfur depletion, comprising: a) providing sulfur-deprived algal culture; b) illuminating culture; c) measuring onset of H.sub.2 percentage in produced gas phase at multiple times to ascertain point immediately after anerobiosis to obtain H.sub.2 data as function of time; and d) determining any abrupt change in three in situ fluorescence parameters; i) increase in F.sub.t (steady-state level of chlorophyll fluorescence in light adapted cells); ii) decrease in F.sub.m', (maximal saturating light induced fluorescence level in light adapted cells); and iii) decrease in .DELTA.F/F.sub.m'=(F.sub.m'-F.sub.t)/F.sub.m' (calculated photochemical activity of photosystem II (PSII) signaling full reduction of plastoquinone pool between PSII and PSI, which indicates start of anaerobic conditions that induces synthesis of hydrogenase enzyme for subsequent H.sub.2 production that signal oxidation of plastoquinone pool asmain factor to regulate H.sub.2 under sulfur depletion.

Acoustic monitoring method and system in laser-induced optical breakdown (LIOB)

DOEpatents

O'Donnell, Matthew [Ann Arbor, MI; Ye, Jing Yong [Ann Arbor, MI; Norris, Theodore B [Dexter, MI; Baker, Jr., James R.; Balogh, Lajos P [Ann Arbor, MI; Milas, Susanne M [Ann Arbor, MI; Emelianov, Stanislav Y [Ann Arbor, MI; Hollman, Kyle W [Fenton, MI

2008-05-06

An acoustic monitoring method and system in laser-induced optical breakdown (LIOB) provides information which characterize material which is broken down, microbubbles in the material, and/or the microenvironment of the microbubbles. In one embodiment of the invention, femtosecond laser pulses are focused just inside the surface of a volume of aqueous solution which may include dendrimer nanocomposite (DNC) particles. A tightly focused, high frequency, single-element ultrasonic transducer is positioned such that its focus coincides axially and laterally with this laser focus. When optical breakdown occurs, a microbubble forms and a shock or pressure wave is emitted (i.e., acoustic emission). In addition to this acoustic signal, the microbubble may be actively probed with pulse-echo measurements from the same transducer. After the microbubble forms, received pulse-echo signals have an extra pulse, describing the microbubble location and providing a measure of axial microbubble size. Wavefield plots of successive recordings illustrate the generation, growth, and collapse of microbubbles due to optical breakdown. These same plots can also be used to quantify LIOB thresholds.

Impact of landslides induced by 2014 northeast monsoon extreme rain in Malaysia

NASA Astrophysics Data System (ADS)

Fukuoka, Hiroshi; Koay, Swee Peng; Sakai, Naoki; Lateh, Habibah

2016-04-01

In December 2014, northeast monsoon brought extreme rainfalls to Malaysia, mainly in the eastern coast of Peninsular Malaysia and coastal area in Sabah and Sarawak. In this month, many of the rain gauge records in this area exceeded 1,000 mm, which is about 1/3 of average annual rainfall precipitation (2,850mm/year) in Malaysia. This unexpected heavy rainfall induced landslides and floods which brought about large-scale losses in Malaysia equivalent to several hundred million USD as thousands of residents had evacuated from hometown for months, and factories, schools and business activities were shut down for weeks. Among the major infrastructure of the nation, East-west Highway was subjected to damages by 21 landslides. Two large-scale landslides cut off the highway for a week. Authors had installed landslide monitoring instruments at reactivated landslide sites along the highway at N05° 36.042' E101° 35.546'. Records by in-situ inclinometers showed clear deformation from 17th December to 26th December, associated with certain change in piezometeres record for groundwater level monitoring. Several cracks occurred in the slope.

Antihyperglycemic and antidyslipidemic activity of Musa paradisiaca-based diet in alloxan-induced diabetic rats.

PubMed

Ajiboye, Basiru O; Oloyede, Hussein O B; Salawu, Musa O

2018-01-01

This study was aimed at investigating the antihyperglycemic and antidyslipidemic activity of Musa paradisiaca -based diets in alloxan-induced diabetic mellitus rats. Diabetes was induced by a single intraperitoneal injection of alloxan (150 mg/kg b.w) in 48 randomly selected rats. The rats were randomly grouped into four as follows: normal rats fed Dioscorea rotundata -based diet, diabetic control rats fed D. rotundata -based diet, diabetic rats fed D. rotundata -based diet and administered metformin (14.2 mg/kg body weight) orally per day, and diabetic rats fed M. paradisiaca -based diet. Body weight and fasting blood glucose level were monitored, on 28th days the rats were sacrificed, liver was excised. Thereafter, the hyperglycemic and dyslipidemic statii of the induced diabetic animals were determined. The M. paradisiaca -based diet significantly ( p  <   .05) reversed the levels of fasting blood glucose, with significant ( p  <   .05) increase in insulin and glycogen concentrations. The diet also increased the activity of hexokinase with significant reduction ( p  <   .05) in glucose-6-phosphatase and fructose-1-6-diphosphatase activities. M. paradisiaca -based diet demonstrated significant reduction ( p  <   .05) in cholesterol, triacylglycerol (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and significant increase ( p  <   .05) in high-density lipoprotein (HDL) compared with those of diabetic control group. Also, M. paradisiaca -based diet significantly ( p  <   .05) reversed the activities of aspartate aminotransferase and alanine aminotransferase when compared with diabetic control animals. The consumption of this diet may be useful in ameliorating hyperglycemia and dyslipidemia in diabetes mellitus patients.

Neurokinin-1 receptor blocker CP-99 994 improved emesis induced by cisplatin via regulating the activity of gastric distention responsive neurons in the dorsal motor nucleus of vagus and enhancing gastric motility in rats.

PubMed

Sun, X; Xu, L; Guo, F; Luo, W; Gao, S; Luan, X

2017-10-01

Nowadays, chemotherapy induced nausea and vomiting (CINV) is still common in patients with cancer. It was reported that substance P mediated CINV via neurokinin-1 (NK 1 ) receptor and antagonists of NK 1 receptor has been proved useful for treating CINV but the mechanism are not fully understood. This study aimed to examine the role of NK 1 receptor blocker, CP-99 994, when administrated into dorsal motor nucleus of vagus (DMNV), on the cisplatin-induced emesis in rats and the possible mechanism. Rats' kaolin intake, food intake, and bodyweight were recorded every day; gastric contraction activity was recorded in conscious rats through a force transducer implanted into the stomach; gastric emptying was monitored using the phenol red method; single unit extracellular firing in the DMNV were recorded. DMNV microinjection of CP-99 994 reduced the changes of increased kaolin consumption and suppressed food intake in cisplatin-treated rats; enhanced the gastric contraction activity dose-dependently in control and cisplatin-treated rats but enhanced gastric emptying only in cisplatin-treated rats; reduced the firing rate of gastric distention inhibited (GD-I) neurons but increased the firing rate of GD excited (GD-E) neurons in the DMNV. The effects of CP-99 994 on gastric motility and neuronal activity were stronger in cisplatin-treated rats than those of control rats. Our results suggested that CP-99 994 could improve emesis induced by cisplatin by regulating gastric motility and gastric related neuronal activity in the DMNV. © 2017 John Wiley & Sons Ltd.

Histaminergic and serotonergic receptor blocking substances from the medicinal plant Garcinia mangostana.

PubMed

Chairungsrilerd, N; Furukawa, K; Ohta, T; Nozoe, S; Ohizumi, Y

1996-10-01

A crude methanolic extract of the fruit hull of Mangosteen, Garcinia mangostana L. inhibited the contractions of isolated thoracic rabbit aorta induced by histamine and serotonin. The extract of the fruit hull has been fractionated by silica gel chromatography, monitoring the pharmacological activity to give alpha- and gamma-mangostin. On the basis of pharmacological data, it is suggested that alpha-mangostin and gamma-mangostin are a histaminergic and a serotonergic receptor blocking agent, respectively.

Hepatoprotective activity of Annona muricata Linn. and Polyalthia cerasoides bedd.

PubMed Central

Padma, P.; Chansouria, J.P.N.; Khosa, R.L.

1999-01-01

The hepatoprotective effect of Annona muricata and Polyalthia cerasoides (Annonaceae) were monitored by estimating the serum transaminases (SGOT and SGPT), serum alkaline phosphatase (SALP), liver and brain lipid peroxidation (LOP) and their total protein content. Both drugs at a dose of 100 μg/kg significantly prevented the increase in serum transaminases, SALP, liver and brain LOP and decrease in liver and brain total protein content following carbontetrachloride (CCl) induced hepatoxicity in albino rats. PMID:22556909

The use of EEG to measure cerebral changes during computer-based motion-sickness-inducing tasks

NASA Astrophysics Data System (ADS)

Strychacz, Christopher; Viirre, Erik; Wing, Shawn

2005-05-01

Motion sickness (MS) is a stressor commonly attributed with causing serious navigational and performance errors. The distinct nature of MS suggests this state may have distinct neural markers distinguishable from other states known to affect performance (e.g., stress, fatigue, sleep deprivation, high workload). This pilot study used new high-resolution electro-encephalograph (EEG) technologies to identify distinct neuronal activation changes that occur during MS. Brain EEG activity was monitored while subjects performed a ball-tracking task and viewed stimuli on a projection screen intended to induce motion sickness/spatial disorientation. Results show the presence of EEG spectral changes in all subjects who developed motion sickness when compared to baseline levels. These changes included: 1) low frequency (1 to 10 Hz) changes that may reflect oculomotor movements rather than intra-cerebral sources; 2) increased spectral power across all frequencies (attributable to increased scalp conductivity related to sweating), 3) local increases of power spectra in the 20-50 Hz range (likely attributable to external muscles on the skull) and; 4) a central posterior (occipital) independent component that shows suppression of a 20 Hz peak in the MS condition when compared to baseline. Further research is necessary to refine neural markers, characterize their origin and physiology, to distinguish between motion sickness and other states and to enable markers to be used for operator state monitoring and the designing of interventions for motion sickness.

Laser activated nanothermolysis of leukemia cells monitored by photothermal microscopy

NASA Astrophysics Data System (ADS)

Lapotko, Dmitri; Lukianova, Ekaterina; Shnip, Alexander; Zheltov, George; Potapnev, Michail; Savitsky, Valeriy; Klimovich, Olga; Oraevsky, Alexander

2005-04-01

We are developing new diagnostic and therapeutic technologies for leukemia based on selective targeting of leukemia cells with gold nanoparticles and thermomechanical destruction of the tumor cells with laser-induced microbubbles. Clusters of spherical gold nanoparticles that have strong optical absorption of laser pulses at 532 nm served as nucleation sites of vapor microbubbles. The nanoparticles were targeted selectively to leukemia cells using leukemia-specific surface receptors and a set of two monoclonal antibodies. Application of a primary myeloid-specific antibody to tumor cells followed by targeting the cells with 30-nm nanoparticles conjugated with a secondary antibody (IgG) resulted in formation of nanoparticulate clusters due to aggregation of IgGs. Formation of clusters resulted in substantial decrease of the damage threshold for target cells. The results encourage development of Laser Activated Nanothermolysis as a Cell Elimination Therapy (LANCET) for leukemia. The proposed technology can be applied separately or in combination with chemotherapy for killing leukemia cells without damage to other blood cells. Potential applications include initial reduction of concentration of leukemia cells in blood prior to chemotherapy and treatment of residual tumor cells after the chemotherapy. Laser-induced bubbles in individual cells and cell damage were monitored by analyzing profile of photothermal response signals over the entire cell after irradiation with a single 10-ns long laser pulse. Photothermal microscopy was utilized for imaging formation of microbubbles around nanoparticulate clusters.

Accurate and rapid modeling of iron-bleomycin-induced DNA damage using tethered duplex oligonucleotides and electrospray ionization ion trap mass spectrometric analysis.

PubMed

Harsch, A; Marzilli, L A; Bunt, R C; Stubbe, J; Vouros, P

2000-05-01

Bleomycin B(2)(BLM) in the presence of iron [Fe(II)] and O(2)catalyzes single-stranded (ss) and double-stranded (ds) cleavage of DNA. Electrospray ionization ion trap mass spectrometry was used to monitor these cleavage processes. Two duplex oligonucleotides containing an ethylene oxide tether between both strands were used in this investigation, allowing facile monitoring of all ss and ds cleavage events. A sequence for site-specific binding and cleavage by Fe-BLM was incorporated into each analyte. One of these core sequences, GTAC, is a known hot-spot for ds cleavage, while the other sequence, GGCC, is a hot-spot for ss cleavage. Incubation of each oligo-nucleotide under anaerobic conditions with Fe(II)-BLM allowed detection of the non-covalent ternary Fe-BLM/oligonucleotide complex in the gas phase. Cleavage studies were then performed utilizing O(2)-activated Fe(II)-BLM. No work-up or separation steps were required and direct MS and MS/MS analyses of the crude reaction mixtures confirmed sequence-specific Fe-BLM-induced cleavage. Comparison of the cleavage patterns for both oligonucleotides revealed sequence-dependent preferences for ss and ds cleavages in accordance with previously established gel electrophoresis analysis of hairpin oligonucleotides. This novel methodology allowed direct, rapid and accurate determination of cleavage profiles of model duplex oligonucleotides after exposure to activated Fe-BLM.

Hesperidin inhibits collagen-induced arthritis possibly through suppression of free radical load and reduction in neutrophil activation and infiltration.

PubMed

Umar, Sadiq; Kumar, Anubhav; Sajad, Mir; Zargan, Jamil; Ansari, Meraj; Ahmad, Sayeed; Katiyar, Chandra Kant; Khan, Haider A

2013-03-01

Rheumatoid arthritis is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone in a chronic phase. Pathology of rheumatoid arthritis suggests autoimmunity linked to inflammation. In our study, rheumatoid arthritis was induced in Wistar rats by intradermal injections of 100 μl of emulsion containing bovine type II collagen in complete Freund's adjuvant at the base of the tail. Disease developed about 13 ± 1 days after immunization and treatment with hesperidin (HES) at a dose of 160 mg kg(-1) body weight was given after onset of disease daily until 20th day. The effect of treatment in the rats was monitored by clinical scoring, biochemical parameters and histological evaluations in joints. A steady increase in the articular elastase, nitric oxide and lipid peroxidation was observed in joints of arthritic rats as compared to control, whereas a significant decrease in reduced glutathione, superoxide dismutase activity and catalase was observed in collagen-induced arthritis rats as compared to control group. The results from the present work indicate that the treatment with hesperidin was effective in bringing about significant changes on all the parameters studied in collagen-induced arthritis rats. These data confirm that erosive destruction of the joint cartilage in collagen-induced arthritis is due free radicals released by activated neutrophils and produced by other biochemical pathways. In the present study, an attempt has been made to amelioration of the disease process by a natural product. These results suggest that oral administration of HES could be effective for treating human RA patients.

Live cell imaging reveals different modes of cytotoxic action of extracts derived from commonly used luting cements.

PubMed

Trumpaitė-Vanagienė, Rita; Čebatariūnienė, Alina; Tunaitis, Virginijus; Pūrienė, Alina; Pivoriūnas, Augustas

2018-02-01

To compare cytotoxicity of extracts derived from commonly used luting cements: Hoffmann's Zinc Phosphate (ZPC), GC Fuji Plus Resin Modified Glass Ionomer (RMGIC) and 3M ESPE RelyX Unicem Resin Cement (RC) on primary human gingival fibroblasts (HGFs). HGFs were exposed to different concentrations of the ZPC, RMGIC and RC extracts. The cytotoxicity was assessed with the PrestoBlue Cell Viability Reagent and viable cells were counted by a haemocytometer using the trypan blue exclusion test. In order to determine the primary mechanism of the cell death induced by extracts from different luting cements, the real-time monitoring of caspase-3/-7 activity and membrane integrity of cells was employed. The extracts from the RMGIC and ZPC decreased the metabolic activity and numbers of viable cells. Unexpectedly, the extracts from the RC evoked only small effects on the metabolic activity of HGFs with a decreasing number of viable cells in a dose-and time-dependent manner. The live cell imaging revealed that the apoptosis was the primary mechanism of a cell death induced by the extracts derived from the RMGIC, whereas the extracts from the RC and ZPC induced a cell death through a necrotic and caspase-independent pathway. The apoptosis was the primary mechanism of the cell death induced by the extracts derived from the RMGIC, whereas the extracts from the RC and ZPC induced a cell death via a necrotic pathway. We suggest that metabolic assays commonly used to assess the cytotoxicity of luting cements should be validated by alternative methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Activation of caspase-3 noninvolved in the bystander effect of the herpes simplex virus thymidine kinase gene/ganciclovir (HSV-tk/GCV) system.

PubMed

Zhang, Zhihong; Lin, Juqiang; Chu, Jun; Ma, Yan; Zeng, Shaoqun; Luo, Qingming

2008-01-01

Use of the herpes simplex virus thymidine kinase gene/ganciclovir (HSV-tk/GCV) system is one of the promising approaches in the rapidly growing area of gene therapy. The "bystander effect," a phenomenon in which HSV-tk+ cells exposed to GCV are toxic to adjacent HSV-tk- cells, was reported to play an important role in suicide gene therapy. However, the mechanism by which HSV-tk/GCV induces the bystander effect is poorly understood. We monitored the activation of caspase-3 in living cells induced by the HSV-tk/GCV system using a genetically encoded fluorescence resonance energy transfer (FRET) probe CD3, , a caspase-3 recognition site fused with a cyan fluorescent protien (CFP) and a red fluorescent protein (DsRed) which we reported and named in a previous paper. Fluorescence protein (FP)-based multicolor cellular labeling, combined with the multichannel fluorescence imaging and FRET imaging techniques, provides a novel and improved approach to directly determine whether the activation of caspase-3 involved in the HSV-tk/GCV system induces cell apoptosis in tk gene-expressing cells and their neighboring cells. FRET ratio images of CD3, and fluorescence images of the fusion protein of thymidine kinase linked with green fluorescent protein (TK-GFP), indicated that HSV-tk/GCV system-induced apoptosis in human adenoid cystic carcinoma (ACC-M) cells was via a caspase-3 pathway, and the activation of caspase-3 was not involved in the bystander effect of HSV-tk/GCV system.

Monitoring environmental effects of shale gas exploitation at Wysin in Poland.

NASA Astrophysics Data System (ADS)

Lasocki, Stanislaw; Mirek, Janusz; Bialon, Wojciech; Cielesta, Szymon; Lasak, Mateusz; Cesca, Simone; Lopez Comino, Jose Angel; Dahm, Torsten; Scarpa, Roberto; Gunning, Andrew; Montcoudiol, Nelly; Isherwood, Catherine; Jaroslawski, Janusz; Guzikowski, Jakub

2017-04-01

Environmental effects of shale gas exploration and exploitation are extensively studied in the framework of "Shale Gas Exploration and Exploitation Induced Risks" project (SHEER, H2020-LCE 16-2014-1). One of the main component of this study is on-site monitoring of the effects at Wysin shale-gas play of Polish Oil and Gas Company in Poland. This includes monitoring of seismicity and water and air quality. Surface seismic monitoring network consists of 6 surface broadband (BB) seismometers and 25 surface short-period (SP) seismometers The SPs are assembled into three small aperture arrays with 9, 8 and 8 stations, respectively, distributed in a triangle geometry at a distance of about 2-4 km from the hydrofracturing rig. Each array is complemented with one BB station. The three remaining BBs are located up to about 5 km from the rig. In addition 3 borehole broadband seismometers are located in three shallow boreholes. The groundwater monitoring makes use of four wells, which reach a main underground water reservoir. Three complementary datasets are collected: continuous monitoring of borehole data, laboratory analyses of water samples and field monitoring of water quality parameters. The continuous monitoring makes use of down-hole probes, which have been installed in each borehole. The probes record absolute pressure, temperature and electrical conductivity. In addition, a barometric probe has been installed above ground to record atmospheric pressure in order to allow conversion of absolute pressure to a water level. After collection, water samples are sent to an accredited laboratory for analysis. The field monitoring is undertaken during the sampling visits. Whilst the borehole is being purged, physico-chemical parameters are monitored using a multi-parameter probe. This measures and records temperature, specific conductivity, pH, dissolved oxygen and oxidation-reduction potential within the water. Hydrocarbon gas content within the water is below detection limits for methane, ethane, ethene and propane gases. Air pollution monitoring is performed by means of an automatic station. The station is situated east from the Wysin rig at the distance of some 1200 m. This distance is appropriate in order not to measure a direct emission of pollutants. The station monitors the content of NO, NO2, NOx, CO, PM10, O3, CO2, CH4, NMHC and Radon. At the beginning of SHEER project in May 2015, there was one vertical well at the site, reaching gas-bearing shale formations at the nearly 4km depth. Further on two horizontal wells, each of about 1.7km length, were drilled (late Autumn 2015) and fracked (June - August, 2016). This time table has provided the opportunity to record background seismicity and baseline levels of water and air quality, and then to record the immediate and delayed effects of hydrofracturing operations. The monitoring will continue at least 1.5 year after completion of technological activity at the site. This work was supported within SHEER: "Shale Gas Exploration and Exploitation Induced Risks" project funded from Horizon 2020 - R&I Framework Programme, call H2020-LCE-2014-1 and within statutory activities No3841/E-41/S/2016 of Ministry of Science and Higher Education of Poland.

The K(ATP)+ channel is involved in a low-amplitude permeability transition in plant mitochondria.

PubMed

Petrussa, Elisa; Casolo, Valentino; Peresson, Carlo; Braidot, Enrico; Vianello, Angelo; Macrì, Francesco

2004-04-01

Pea (Pisum sativum) stem mitochondria, energized by NADH, succinate or malate plus glutamate, underwent a spontaneous low-amplitude permeability transition (PT), which could be monitored by dissipation of the electrical potential (deltapsi) or swelling. The occurrence of the latter effects was dependent on O2 availability, because O2 shortage anticipated the manifestation of both deltapsi dissipation and swelling. Spontaneous deltapsi collapse was also monitored in sucrose-resuspended mitochondria and again O2 deprivation caused an anticipation of the phenomenon. However, in this case deltapsi dissipation was not accompanied by a parallel mitochondrial swelling. The latter effect was, indeed, evident only if mitochondria were resuspended in KCl (as osmoticum), or other cations with a molecular mass up to 100 Da (choline+). PT was also induced by protonophores (carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) or free fatty acids) or valinomycin (only in KCl). The FCCP-induced dissipation of deltapsi and swelling were inhibited by ATP and stimulated (anticipated) by cyclosporin A or O2 shortage. The FCCP-induced PT was accompanied by the release of pyridine nucleotides from the matrix and of cytochrome c from the intermembrane space of KCl-resuspended mitochondria. The spontaneous and FCCP-induced low-amplitude PT of plant mitochondria are interpreted as due to the activity of a recently identified K(ATP)+ channel whose open/closed state is dependent on polarization of the inner membrane and on the oxidoreductive state of some sulfhydryl groups.

A new infusion pathway intactness monitoring system.

PubMed

Ogawa, Hidekuni; Yonezawa, Yoshiharu; Maki, Hiromichi; Ninomiya, Ishio; Sata, Koji; Hamada, Shingo; Caldwell, W Morton

2006-01-01

A new infusion pathway monitoring system has been developed for hospital and home use. The system consists of linear integrated circuits and a low-power 8-bit single chip microcomputer which constantly monitors the infusion pathway intactness. An AC (alternating current) voltage is induced on the patient's body by electrostatic coupling from the normal 100 volt, 60 Hz AC power line wiring field in the patient's room. The induced AC voltage can be recorded by a main electrode wrapped around the infusion polyvinyl chloride tube. A reference electrode is wrapped on the electrode to monitor the AC voltage around the main electrode. If the injection needle or infusion tube becomes detached, then the system detects changes in the induced AC voltages and alerts the nursing station, via the nurse call system or PHS (personal handy phone system).

Dietary Supplementation of Fermented Rice Bran Effectively Alleviates Dextran Sodium Sulfate-Induced Colitis in Mice.

PubMed

Islam, Jahidul; Koseki, Takuya; Watanabe, Kouichi; Budijanto, Slamet; Oikawa, Akira; Alauddin, Md; Goto, Tomoko; Aso, Hisahi; Komai, Michio; Shirakawa, Hitoshi

2017-07-13

Rice bran (RB) is a major by-product of rice polishing and a rich source of bioactive compounds. Here, we investigated the anti-colitis effect of diet supplementation with fermented rice bran (FRB) in a murine model of ulcerative colitis. FRB was prepared by dual fermentation of RB using fungi and lactic acid bacteria. Colitis was induced in C57Bl/6N male mice ( n = 8/group) by dextran sodium sulfate (DSS). Body weight change, disease activity index (DAI), histopathology score, tissue myeloperoxidase (MPO) activity, cytokine and chemokine transcript levels, and the production of short-chain fatty acids (SCFAs) and mucin in the colonic tissue were monitored. Based on histopathology scores, DSS induced severe mucosal inflammation, with an increased loss of crypts, and inflammatory cell infiltration in the control and RB groups, but not in the FRB group. MPO activity, thiobarbituric acid-reactive substance levels, and pro-inflammatory cytokine transcript ( Tnf-α , Il-1β , Il-6 , and Il-17 ) levels were significantly higher in the control and RB groups than in the FRB group. Thus, dietary FRB attenuated intestinal inflammation owing to elevated SCFAs and tryptamine production, which might regulate tight junction barrier integrity and intestinal homeostasis. These results suggest that FRB could comprise an effective potential preventive agent for ulcerative colitis.

Whole-cell MALDI-TOF MS: a new tool to assess the multifaceted activation of macrophages.

PubMed

Ouedraogo, Richard; Daumas, Aurélie; Ghigo, Eric; Capo, Christian; Mege, Jean-Louis; Textoris, Julien

2012-10-22

Whole-cell MALDI-TOF MS is routinely used to identify bacterial species in clinical samples. This technique has also proven to allow identification of intact mammalian cells, including macrophages. Here, we wondered whether this approach enabled the assessment human macrophages plasticity. The whole-cell MALDI-TOF spectra of macrophages stimulated with IFN-γ and IL-4, two inducers of M1 and M2 macrophage polarisation, consisted of peaks ranging from 2 to 12 kDa. The spectra of unstimulated and stimulated macrophages were clearly different. The fingerprints induced by the M1 agonists, IFN-γ, TNF, LPS and LPS+IFN-γ, and the M2 agonists, IL-4, TGF-β1 and IL-10, were specific and readily identifiable. Thus, whole-cell MALDI-TOF MS was able to characterise M1 and M2 macrophage subtypes. In addition, the fingerprints induced by extracellular (group B Streptococcus, Staphylococcus aureus) or intracellular (BCG, Orientia tsutsugamushi, Coxiella burnetii) bacteria were bacterium-specific. The whole-cell MALDI-TOF MS fingerprints therefore revealed the multifaceted activation of human macrophages. This approach opened a new avenue of studies to assess the immune response in the clinical setting, by monitoring the various activation patterns of immune cells in pathological conditions. Copyright © 2012 Elsevier B.V. All rights reserved.

Butyrate-induced proapoptotic and antiangiogenic pathways in EAT cells require activation of CAD and downregulation of VEGF

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belakavadi, Madesh; Prabhakar, B.T.; Salimath, Bharathi P.

Butyrate, a short-chain fatty acid produced in the colon, induces cell cycle arrest, differentiation, and apoptosis in transformed cell lines. In this report, we study the effects of butyrate (BuA) on the growth of Ehrlich ascites tumor (EAT) cells in vivo. BuA, when injected intraperitoneally (i.p) into mice, inhibited proliferation of EAT cells. Further, induction of apoptosis in EAT cells was monitored by nuclear condensation, annexin-V staining, DNA fragmentation, and translocation of caspase-activated DNase into nucleus upon BuA-treatment. Ac-DEVD-CHO, a caspase-3 inhibitor, completely inhibited BuA-induced apoptosis, indicating that activation of caspase-3 mediates the apoptotic pathway in EAT cells. The proapoptoticmore » effect of BuA also reflects on the antiangiogenic pathway in EAT cells. The antiangiogenic effect of BuA in vivo was demonstrated by the downregulation of the secretion of VEGF in EAT cells. CD31 immunohistochemical staining of peritoneum sections clearly indicated a potential angioinhibitory effect of BuA in EAT cells. These results suggest that BuA, besides regulating other fundamental cellular processes, is able to modulate the expression/secretion of the key angiogenic growth factor VEGF in EAT cells.« less

Differences between Angus and Holstein cattle in the Lupinus leucophyllus induced inhibition of fetal activity.

PubMed

Green, Benedict T; Panter, Kip E; Lee, Stephen T; Welch, Kevin D; Pfister, James A; Gardner, Dale R; Stegelmeier, Bryan L; Davis, T Zane

2015-11-01

Calves with congenital defects born to cows that have grazed teratogenic Lupinus spp. during pregnancy can suffer from what is termed crooked calf syndrome. Crooked calf syndrome defects include cleft palate, spinal column defects and limb malformations formed by alkaloid-induced inhibition of fetal movement. In this study, we tested the hypothesis that there are differences in fetal activity of fetuses carried by Holstein verses Angus heifers orally dosed with 1.1 g/kg dried ground Lupinus leucophyllus. Fetal activity was monitored via transrectal ultrasonography and maternal serum was analyzed for specific lupine alkaloids. There were more (P < 0.05) movements in fetuses of Holstein heifers than those in Angus heifers at eight and 12 h after oral dosing. In addition to serum alkaloid toxicokinetic differences, the Holstein heifers had significantly lower serum concentrations of anagyrine at 2, 4, and 8 h after oral dosing than Angus heifers. Holstein heifers also had significantly greater serum concentrations of lupanine at 12, 18 and 24 h after dosing than the Angus heifers. These results suggest that there are breed differences in susceptibility to lupine-induced crooked calf syndrome. These differences may also be used to discover genetic markers that identify resistant animals, thus facilitating selective breeding of resistant herds. Published by Elsevier Ltd.

Insulin Induces an Increase in Cytosolic Glucose Levels in 3T3-L1 Cells with Inhibited Glycogen Synthase Activation

PubMed Central

Chowdhury, Helena H.; Kreft, Marko; Jensen, Jørgen; Zorec, Robert

2014-01-01

Glucose is an important source of energy for mammalian cells and enters the cytosol via glucose transporters. It has been thought for a long time that glucose entering the cytosol is swiftly phosphorylated in most cell types; hence the levels of free glucose are very low, beyond the detection level. However, the introduction of new fluorescence resonance energy transfer-based glucose nanosensors has made it possible to measure intracellular glucose more accurately. Here, we used the fluorescent indicator protein (FLIPglu-600µ) to monitor cytosolic glucose dynamics in mouse 3T3-L1 cells in which glucose utilization for glycogen synthesis was inhibited. The results show that cells exhibit a low resting cytosolic glucose concentration. However, in cells with inhibited glycogen synthase activation, insulin induced a robust increase in cytosolic free glucose. The insulin-induced increase in cytosolic glucose in these cells is due to an imbalance between the glucose transported into the cytosol and the use of glucose in the cytosol. In untreated cells with sensitive glycogen synthase activation, insulin stimulation did not result in a change in the cytosolic glucose level. This is the first report of dynamic measurements of cytosolic glucose levels in cells devoid of the glycogen synthesis pathway. PMID:25279585

Dietary Supplementation of Fermented Rice Bran Effectively Alleviates Dextran Sodium Sulfate-Induced Colitis in Mice

PubMed Central

Islam, Jahidul; Koseki, Takuya; Watanabe, Kouichi; Ardiansyah; Budijanto, Slamet; Oikawa, Akira; Alauddin, Md; Goto, Tomoko; Aso, Hisahi; Komai, Michio; Shirakawa, Hitoshi

2017-01-01

Rice bran (RB) is a major by-product of rice polishing and a rich source of bioactive compounds. Here, we investigated the anti-colitis effect of diet supplementation with fermented rice bran (FRB) in a murine model of ulcerative colitis. FRB was prepared by dual fermentation of RB using fungi and lactic acid bacteria. Colitis was induced in C57Bl/6N male mice (n = 8/group) by dextran sodium sulfate (DSS). Body weight change, disease activity index (DAI), histopathology score, tissue myeloperoxidase (MPO) activity, cytokine and chemokine transcript levels, and the production of short-chain fatty acids (SCFAs) and mucin in the colonic tissue were monitored. Based on histopathology scores, DSS induced severe mucosal inflammation, with an increased loss of crypts, and inflammatory cell infiltration in the control and RB groups, but not in the FRB group. MPO activity, thiobarbituric acid-reactive substance levels, and pro-inflammatory cytokine transcript (Tnf-α, Il-1β, Il-6, and Il-17) levels were significantly higher in the control and RB groups than in the FRB group. Thus, dietary FRB attenuated intestinal inflammation owing to elevated SCFAs and tryptamine production, which might regulate tight junction barrier integrity and intestinal homeostasis. These results suggest that FRB could comprise an effective potential preventive agent for ulcerative colitis. PMID:28703759

7 CFR 3560.352 - Agency monitoring scope, purpose, and borrower responsibilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... monitoring activities. The Agency will review reports, records, and other materials related to the housing...) Purpose of Agency monitoring activities. Agency monitoring activities are designed to assess borrower and... responsible for cooperating fully and promptly with Agency monitoring activities. Agency monitoring activities...

7 CFR 3560.352 - Agency monitoring scope, purpose, and borrower responsibilities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... monitoring activities. The Agency will review reports, records, and other materials related to the housing...) Purpose of Agency monitoring activities. Agency monitoring activities are designed to assess borrower and... responsible for cooperating fully and promptly with Agency monitoring activities. Agency monitoring activities...

7 CFR 3560.352 - Agency monitoring scope, purpose, and borrower responsibilities.

Code of Federal Regulations, 2013 CFR

2013-01-01

... monitoring activities. The Agency will review reports, records, and other materials related to the housing...) Purpose of Agency monitoring activities. Agency monitoring activities are designed to assess borrower and... responsible for cooperating fully and promptly with Agency monitoring activities. Agency monitoring activities...

7 CFR 3560.352 - Agency monitoring scope, purpose, and borrower responsibilities.

Code of Federal Regulations, 2014 CFR

2014-01-01

... monitoring activities. The Agency will review reports, records, and other materials related to the housing...) Purpose of Agency monitoring activities. Agency monitoring activities are designed to assess borrower and... responsible for cooperating fully and promptly with Agency monitoring activities. Agency monitoring activities...

7 CFR 3560.352 - Agency monitoring scope, purpose, and borrower responsibilities.

Code of Federal Regulations, 2012 CFR

2012-01-01

... monitoring activities. The Agency will review reports, records, and other materials related to the housing...) Purpose of Agency monitoring activities. Agency monitoring activities are designed to assess borrower and... responsible for cooperating fully and promptly with Agency monitoring activities. Agency monitoring activities...

Longitudinal monitoring of Gaussia and Nano luciferase activities to concurrently assess ER calcium homeostasis and ER stress in vivo.

PubMed

Wires, Emily S; Henderson, Mark J; Yan, Xiaokang; Bäck, Susanne; Trychta, Kathleen A; Lutrey, Molly H; Harvey, Brandon K

2017-01-01

The endoplasmic reticulum (ER) is essential to many cellular processes including protein processing, lipid metabolism and calcium storage. The ability to longitudinally monitor ER homeostasis in the same organism would offer insight into progressive molecular and cellular adaptations to physiologic or pathologic states, but has been challenging. We recently described the creation of a Gaussia luciferase (GLuc)-based secreted ER calcium-modulated protein (SERCaMP or GLuc-SERCaMP) to longitudinally monitor ER calcium homeostasis. Here we describe a complementary tool to measure the unfolded protein response (UPR), utilizing a UPRE-driven secreted Nano luciferase (UPRE-secNLuc) to examine the activating transcription factor-6 (ATF6) and inositol-requiring enzyme 1 (IRE1) pathways of the UPR. We observed an upregulation of endogenous ATF6- and XBP1-regulated genes following pharmacologically-induced ER stress that was consistent with responsiveness of the UPRE sensor. Both GLuc and NLuc-based reporters have favorable properties for in vivo studies, however, they are not easily used in combination due to overlapping substrate activities. We describe a method to measure the enzymatic activities of both reporters from a single sample and validated the approach using culture medium and rat blood samples to measure GLuc-SERCaMP and UPRE-secNLuc. Measuring GLuc and NLuc activities from the same sample allows for the robust and quantitative measurement of two cellular events or cell populations from a single biological sample. This study is the first to describe the in vivo measurement of UPRE activation by sampling blood, using an approach that allows concurrent interrogation of two components of ER homeostasis.

Monitoring Concrete Deterioration Due to Reinforcement Corrosion by Integrating Acoustic Emission and FBG Strain Measurements

PubMed Central

Li, Weijie; Xu, Changhang; Ho, Siu Chun Michael; Wang, Bo; Song, Gangbing

2017-01-01

Corrosion of concrete reinforcement members has been recognized as a predominant structural deterioration mechanism for steel reinforced concrete structures. Many corrosion detection techniques have been developed for reinforced concrete structures, but a dependable one is more than desired. Acoustic emission technique and fiber optic sensing have emerged as new tools in the field of structural health monitoring. In this paper, we present the results of an experimental investigation on corrosion monitoring of a steel reinforced mortar block through combined acoustic emission and fiber Bragg grating strain measurement. Constant current was applied to the mortar block in order to induce accelerated corrosion. The monitoring process has two aspects: corrosion initiation and crack propagation. Propagation of cracks can be captured through corresponding acoustic emission whereas the mortar expansion due to the generation of corrosion products will be monitored by fiber Bragg grating strain sensors. The results demonstrate that the acoustic emission sources comes from three different types, namely, evolution of hydrogen bubbles, generation of corrosion products and crack propagation. Their corresponding properties are also discussed. The results also show a good correlation between acoustic emission activity and expansive strain measured on the specimen surface. PMID:28327510

Monitoring Concrete Deterioration Due to Reinforcement Corrosion by Integrating Acoustic Emission and FBG Strain Measurements.

PubMed

Li, Weijie; Xu, Changhang; Ho, Siu Chun Michael; Wang, Bo; Song, Gangbing

2017-03-22

Corrosion of concrete reinforcement members has been recognized as a predominant structural deterioration mechanism for steel reinforced concrete structures. Many corrosion detection techniques have been developed for reinforced concrete structures, but a dependable one is more than desired. Acoustic emission technique and fiber optic sensing have emerged as new tools in the field of structural health monitoring. In this paper, we present the results of an experimental investigation on corrosion monitoring of a steel reinforced mortar block through combined acoustic emission and fiber Bragg grating strain measurement. Constant current was applied to the mortar block in order to induce accelerated corrosion. The monitoring process has two aspects: corrosion initiation and crack propagation. Propagation of cracks can be captured through corresponding acoustic emission whereas the mortar expansion due to the generation of corrosion products will be monitored by fiber Bragg grating strain sensors. The results demonstrate that the acoustic emission sources comes from three different types, namely, evolution of hydrogen bubbles, generation of corrosion products and crack propagation. Their corresponding properties are also discussed. The results also show a good correlation between acoustic emission activity and expansive strain measured on the specimen surface.

Full-scale monitoring of wind and suspension bridge response

NASA Astrophysics Data System (ADS)

Snæbjörnsson, J. T.; Jakobsen, J. B.; Cheynet, E.; Wang, J.

2017-12-01

Monitoring of real structures is important for many reasons. For structures susceptible to environmental actions, full-scale observations can provide valuable information about the environmental conditions at the site, as well as the characteristics of the excitation acting on the structure. The recorded data, if properly analyzed, can be used to validate and/or update experiments and models used in the design of new structures, such as the load description and modelling of the structural response. Various aspects of full-scale monitoring are discussed in the paper and the full-scale wind engineering laboratory at the Lysefjord suspension bridge introduced. The natural excitation of the bridge comes from wind and traffic. The surrounding terrain is complex and its effect on the wind flow can only be fully studied on site, in full-scale. The monitoring program and associated data analysis are described. These include various studies of the relevant turbulence characteristics, identification of dynamic properties and estimation of wind- and traffic-induced response parameters. The overall monitoring activity also included a novel application of the remote optical sensing in bridge engineering, which is found to have an important potential to complement traditional “single-point” wind observations by sonic anemometers.

Artifactual ECG changes induced by electrocautery in a patient with coronary artery disease.

PubMed

Naik, B Naveen; Luthra, Ankur; Dwivedi, Ashish; Jafra, Anudeep

Continuous monitoring of 5-lead electrocardiogram is a basic standard of care (included under standard ASA monitor) in the operating room and electrocautery interference is a common phenomenon. Clinical signs, along with monitored waveforms from other simultaneously monitored parameters may provide us clues to differentiate artifacts from true changes on the electrocardiogram. An improved understanding of the artifacts generated by electrocautery and their identifying characteristics is important to avoid misinterpretation, misdiagnosis, and hence mismanagement. This case report highlights the artifacts in electrocardiogram induced by electrocautery. Copyright © 2017 Elsevier Inc. All rights reserved.

Opiate-induced seizures: a study of mu and delta specific mechanisms.

PubMed

Snead, O C

1986-08-01

Two groups of experiments were conducted to determine if morphine- and enkephalin-induced seizures are specifically mediated by the mu and delta receptor, respectively. In the first experiments, designed to assess the ontogeny of mu- or delta-seizures, rats from 6 h to 85 days of age received implanted cortical and depth electrodes as well as an indwelling cannula in the lateral ventricle. Various amounts of the mu-receptor agonists, morphine and morphiceptin, and the delta agonists, D-Ala2-D-Leu5-enkephalin (DADL) and Tyr-D-Ser-Gly-Phe-Leu-Thr (DSLET), were then administered intracerebroventricularly (icv) with continuous EEG monitoring. The second experiments entailed use of the nonspecific opiate antagonist, naloxone, as well as the specific delta antagonist, ICI 154,129, against seizures induced by icv-administered morphine, morphiceptin, DADL, or DSLET. Both morphine and morphiceptin produced electrical seizure activity in rats as young as 5 days after birth. The drugs produced similar seizure activity in terms of electrical morphology, observed behavior, ontogeny, threshold dose, and reversibility with small doses of naloxone. In the pharmacologic experiments, icv naloxone blocked all opiate-induced seizures. ICI 154,129 blocked DSLET seizure, had little effect on enkephalin or DADL seizures, and no effect on morphine or morphiceptin seizures. These data indicate that DSLET seizures are delta-specific but that all other opiate-induced seizures studied may involve multiple opiate receptor-mediated mechanisms.

Assessing the sensitivity of diffusion MRI to detect neuronal activity directly.

PubMed

Bai, Ruiliang; Stewart, Craig V; Plenz, Dietmar; Basser, Peter J

2016-03-22

Functional MRI (fMRI) is widely used to study brain function in the neurosciences. Unfortunately, conventional fMRI only indirectly assesses neuronal activity via hemodynamic coupling. Diffusion fMRI was proposed as a more direct and accurate fMRI method to detect neuronal activity, yet confirmative findings have proven difficult to obtain. Given that the underlying relation between tissue water diffusion changes and neuronal activity remains unclear, the rationale for using diffusion MRI to monitor neuronal activity has yet to be clearly established. Here, we studied the correlation between water diffusion and neuronal activity in vitro by simultaneous calcium fluorescence imaging and diffusion MR acquisition. We used organotypic cortical cultures from rat brains as a biological model system, in which spontaneous neuronal activity robustly emerges free of hemodynamic and other artifacts. Simultaneous fluorescent calcium images of neuronal activity are then directly correlated with diffusion MR signals now free of confounds typically encountered in vivo. Although a simultaneous increase of diffusion-weighted MR signals was observed together with the prolonged depolarization of neurons induced by pharmacological manipulations (in which cell swelling was demonstrated to play an important role), no evidence was found that diffusion MR signals directly correlate with normal spontaneous neuronal activity. These results suggest that, whereas current diffusion MR methods could monitor pathological conditions such as hyperexcitability, e.g., those seen in epilepsy, they do not appear to be sensitive or specific enough to detect or follow normal neuronal activity.

Assessing the sensitivity of diffusion MRI to detect neuronal activity directly

PubMed Central

Bai, Ruiliang; Stewart, Craig V.; Plenz, Dietmar; Basser, Peter J.

2016-01-01

Functional MRI (fMRI) is widely used to study brain function in the neurosciences. Unfortunately, conventional fMRI only indirectly assesses neuronal activity via hemodynamic coupling. Diffusion fMRI was proposed as a more direct and accurate fMRI method to detect neuronal activity, yet confirmative findings have proven difficult to obtain. Given that the underlying relation between tissue water diffusion changes and neuronal activity remains unclear, the rationale for using diffusion MRI to monitor neuronal activity has yet to be clearly established. Here, we studied the correlation between water diffusion and neuronal activity in vitro by simultaneous calcium fluorescence imaging and diffusion MR acquisition. We used organotypic cortical cultures from rat brains as a biological model system, in which spontaneous neuronal activity robustly emerges free of hemodynamic and other artifacts. Simultaneous fluorescent calcium images of neuronal activity are then directly correlated with diffusion MR signals now free of confounds typically encountered in vivo. Although a simultaneous increase of diffusion-weighted MR signals was observed together with the prolonged depolarization of neurons induced by pharmacological manipulations (in which cell swelling was demonstrated to play an important role), no evidence was found that diffusion MR signals directly correlate with normal spontaneous neuronal activity. These results suggest that, whereas current diffusion MR methods could monitor pathological conditions such as hyperexcitability, e.g., those seen in epilepsy, they do not appear to be sensitive or specific enough to detect or follow normal neuronal activity. PMID:26941239

Hydraulic Fracture Induced Seismicity During A Multi-Stage Pad Completion in Western Canada: Evidence of Activation of Multiple, Parallel Faults

NASA Astrophysics Data System (ADS)

Maxwell, S.; Garrett, D.; Huang, J.; Usher, P.; Mamer, P.

2017-12-01

Following reports of injection induced seismicity in the Western Canadian Sedimentary Basin, regulators have imposed seismic monitoring and traffic light protocols for fracturing operations in specific areas. Here we describe a case study in one of these reservoirs, the Montney Shale in NE British Columbia, where induced seismicity was monitored with a local array during multi-stage hydraulic fracture stimulations on several wells from a single drilling pad. Seismicity primarily occurred during the injection time periods, and correlated with periods of high injection rates and wellhead pressures above fracturing pressures. Sequential hydraulic fracture stages were found to progressively activate several parallel, critically-stressed faults, as illuminated by multiple linear hypocenter patterns in the range between Mw 1 and 3. Moment tensor inversion of larger events indicated a double-couple mechanism consistent with the regional strike-slip stress state and the hypocenter lineations. The critically-stressed faults obliquely cross the well paths which were purposely drilled parallel to the minimum principal stress direction. Seismicity on specific faults started and stopped when fracture initiation points of individual injection stages were proximal to the intersection of the fault and well. The distance ranges when the seismicity occurs is consistent with expected hydraulic fracture dimensions, suggesting that the induced fault slip only occurs when a hydraulic fracture grows directly into the fault and the faults are temporarily exposed to significantly elevated fracture pressures during the injection. Some faults crossed multiple wells and the seismicity was found to restart during injection of proximal stages on adjacent wells, progressively expanding the seismogenic zone of the fault. Progressive fault slip is therefore inferred from the seismicity migrating further along the faults during successive injection stages. An accelerometer was also deployed close to the pad operations providing information about the local ground motion at near offsets, although no ground motion was recorded that exceeds the minimum levels requiring mandatory reporting to the regulator.

Usefulness of simultaneous and sequential monitoring of glucose level and electrocardiogram in monkeys treated with gatifloxacin under conscious and nonrestricted conditions.

PubMed

Yoshimatsu, Yu; Ishizaka, Tomomichi; Chiba, Katsuyoshi; Mori, Kazuhiko

2018-05-10

Drug-induced cardiac electrophysiological abnormalities accompanied by hypoglycemia or hyperglycemia increase the risk for life-threatening arrhythmia. To assess the drug-induced cardiotoxic potential associated with extraordinary blood glucose (GLU) levels, the effect of gatifloxacin (GFLX) which was frequently associated with GLU abnormality and QT/QTc prolongations in the clinic on blood GLU and electrocardiogram (ECG) parameters was investigated in cynomolgus monkeys (n=4) given GFLX orally in an ascending dose regimen (10, 30, 60 and 100 mg/kg). Simultaneous and sequential GLU and ECG monitoring with a continuous GLU monitoring system and Holter ECG, respectively, were conducted for 24 h under free-moving conditions. Consequently, GFLX at 30 and 60 mg/kg dose-dependently induced a transient decrease in GLU without any ECG abnormality 2-4 h postdose. Highest dose of 100 mg/kg caused severe hypoglycemia with a mean GLU of <30 mg/dL, accompanied by remarkable QT/QTc prolongations by 20-30% in all animals. In contrast, hyperglycemia without QT/QTc prolongations was noted 24 h after dosing in one animal. A close correlation between GLU and QTc values was observed in animals treated with 100 mg/kg, suggesting that GFLX-induced hypoglycemia enhanced QT/QTc prolongations. Furthermore, the 24-h sequential GLU monitoring data clearly distinguished between GFLX-induced GLU abnormality and physiological GLU changes influenced by feeding throughout the day. In conclusion, the combined assessment of continuous GLU and ECG monitoring is valuable in predicting the drug-induced cardio-electrophysiological risk associated with both GLU and ECG abnormalities.

Adiponectin Enhances the Responsiveness of the Olfactory System

PubMed Central

Loch, Diana; Heidel, Christian; Breer, Heinz; Strotmann, Jörg

2013-01-01

The peptide hormone adiponectin is secreted by adipose tissue and the circulating concentration is reversely correlated with body fat mass; it is considered as starvation signal. The observation that mature sensory neurons of the main olfactory epithelium express the adiponectin receptor 1 has led to the concept that adiponectin may affect the responsiveness of the olfactory system. In fact, electroolfactogram recordings from olfactory epithelium incubated with exogenous adiponectin resulted in large amplitudes upon odor stimulation. To determine whether the responsiveness of the olfactory sensory neurons was enhanced, we have monitored the odorant-induced expression of the immediate early gene Egr1. It was found that in an olfactory epithelium incubated with nasally applied adiponectin the number of Egr1 positive cells was significantly higher compared to controls, suggesting that adiponectin rendered the olfactory neurons more responsive to an odorant stimulus. To analyze whether the augmented responsiveness of sensory neurons was strong enough to elicit a higher neuronal activity in the olfactory bulb, the number of activated periglomerular cells of a distinct glomerulus was determined by monitoring the stimulus-induced expression of c-fos. The studies were performed using the transgenic mOR256-17-IRES-tauGFP mice which allowed to visualize the corresponding glomerulus and to stimulate with a known ligand. The data indicate that upon exposure to 2,3-hexanedione in adiponectin-treated mice the number of activated periglomerular neurons was significantly increased compared to controls. The results of this study indicate that adiponectin increases the responsiveness of the olfactory system, probably due to a higher responsiveness of olfactory sensory neurons. PMID:24130737

Induced senescence promotes the feeding activities and nymph development of Myzus persicae (Hemiptera: Aphididae) on potato plants.

PubMed

Machado-Assefh, Cristina R; Lucatti, Alejandro F; Alvarez, Adriana E

2014-01-01

The effect of dark-induced senescence on Solanum tuberosum L. (Solanales: Solanaceae) plants was assessed on the feeding behavior and performance of the green peach aphid, Myzus persicae Sulzer (Hemiptera: Aphididae). Senescence was induced by covering the basal part of the plant with a black cloth for 5 d, avoiding the light passage, but keeping the apical buds uncovered. The basal part of control plants was covered with a white nonwoven cloth. The degree of senescence was determined by measuring the chlorophyll content of the covered leaves. The performance and feeding behavior of M. persicae were studied on the uncovered nonsenescent apical leaves. The aphid's performance was evaluated by measuring nymphal mortality and prereproductive time. Aphid feeding behavior was monitored by the electrical penetration graph technique. In plants with dark-induced senescence, the aphids showed a reduction in their prereproductive time. Aphids also spent more time ingesting sap from the phloem than in control plants and performed more test probes after the first sustained ingestion of phloem sap. These data suggest that M. persicae's phloem activities and nymph development benefit from the nutritional enrichment of phloem sap, derived from dark-induced senescence on potato plants. The induced senescence improved plant acceptance by M. persicae through an increase in sap ingestion that likely resulted in a reduction in developmental time. © The Author 2014. Published by Oxford University Press on behalf of the Entomological Society of America.

Picking vs Waveform based detection and location methods for induced seismicity monitoring

NASA Astrophysics Data System (ADS)

Grigoli, Francesco; Boese, Maren; Scarabello, Luca; Diehl, Tobias; Weber, Bernd; Wiemer, Stefan; Clinton, John F.

2017-04-01

Microseismic monitoring is a common operation in various industrial activities related to geo-resouces, such as oil and gas and mining operations or geothermal energy exploitation. In microseismic monitoring we generally deal with large datasets from dense monitoring networks that require robust automated analysis procedures. The seismic sequences being monitored are often characterized by very many events with short inter-event times that can even provide overlapped seismic signatures. In these situations, traditional approaches that identify seismic events using dense seismic networks based on detections, phase identification and event association can fail, leading to missed detections and/or reduced location resolution. In recent years, to improve the quality of automated catalogues, various waveform-based methods for the detection and location of microseismicity have been proposed. These methods exploit the coherence of the waveforms recorded at different stations and do not require any automated picking procedure. Although this family of methods have been applied to different induced seismicity datasets, an extensive comparison with sophisticated pick-based detection and location methods is still lacking. We aim here to perform a systematic comparison in term of performance using the waveform-based method LOKI and the pick-based detection and location methods (SCAUTOLOC and SCANLOC) implemented within the SeisComP3 software package. SCANLOC is a new detection and location method specifically designed for seismic monitoring at local scale. Although recent applications have proved an extensive test with induced seismicity datasets have been not yet performed. This method is based on a cluster search algorithm to associate detections to one or many potential earthquake sources. On the other hand, SCAUTOLOC is more a "conventional" method and is the basic tool for seismic event detection and location in SeisComp3. This approach was specifically designed for regional and teleseismic applications, thus its performance with microseismic data might be limited. We analyze the performance of the three methodologies for a synthetic dataset with realistic noise conditions as well as for the first hour of continuous waveform data, including the Ml 3.5 St. Gallen earthquake, recorded by a microseismic network deployed in the area. We finally compare the results obtained all these three methods with a manually revised catalogue.

Role of cytokines (TNF-alpha, IL-1beta and KC) in the pathogenesis of CPT-11-induced intestinal mucositis in mice: effect of pentoxifylline and thalidomide.

PubMed

Melo, Maria Luisa P; Brito, Gerly A C; Soares, Rudy C; Carvalho, Sarah B L M; Silva, Johan V; Soares, Pedro M G; Vale, Mariana L; Souza, Marcellus H L P; Cunha, Fernando Q; Ribeiro, Ronaldo A

2008-04-01

Irinotecan (CPT-11) is an inhibitor of DNA topoisomerase I and is clinically effective against several cancers. A major toxic effect of CPT-11 is delayed diarrhea; however, the exact mechanism by which the drug induces diarrhea has not been established. Elucidate the mechanisms of induction of delayed diarrhea and determine the effects of the cytokine production inhibitor pentoxifylline (PTX) and thalidomide (TLD) in the experimental model of intestinal mucositis, induced by CPT-11. Intestinal mucositis was induced in male Swiss mice by intraperitoneal administration of CPT-11 (75 mg/kg) daily for 4 days. Animals received subcutaneous PTX (1.7, 5 and 15 mg/kg) or TLD (15, 30, 60 mg/kg) or 0.5 ml of saline daily for 5 and 7 days, starting 1 day before the first CPT-11 injection. The incidence of delayed diarrhea was monitored by scores and the animals were sacrificed on the 5th and 7th experimental day for histological analysis, immunohistochemistry for TNF-alpha and assay of myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and KC ELISA. CPT-11 caused significant diarrhea, histopathological alterations (inflammatory cell infiltration, loss of crypt architecture and villus shortening) and increased intestinal tissue MPO activity, TNF-alpha, IL-1beta and KC level and TNF-alpha immuno-staining. PTX inhibited delayed diarrhea of mice submitted to intestinal mucositis and reduced histopathological damage, intestinal MPO activity, tissue level of TNF-alpha, IL-1beta and KC and TNF-alpha immuno-staining. TLD significantly reduced the lesions induced by CPT-11 in intestinal mucosa, decreased MPO activity, TNF-alpha tissue level and TNF-alpha immuno-staining, but did not reduce the severity of diarrhea. These results suggest an important role of TNF-alpha, IL-1beta and KC in the pathogenesis of intestinal mucositis induced by CPT-11.

Tumor Mechanics and Metabolic Dysfunction

PubMed Central

Tung, Jason C.; Barnes, J. Matthew; Desai, Shraddha R.; Sistrunk, Christopher; Conklin, Matthew; Schedin, Pepper; Keely, Patricia J.; Seewaldt, Victoria L.; Weaver, Valerie M.

2015-01-01

Desmosplasia is a characteristic of most solid tumors and leads to fibrosis through abnormal extracellular matrix (ECM) deposition, remodeling and post translational modifications. The resulting stiff tumor stroma not only compromises vascular integrity to induce hypoxia and impede drug delivery, but also promotes aggressiveness by potentiating the activity of key growth, invasion, and survival pathways. Intriguingly, many of the pro-tumorigenic signaling pathways which are mechanically activated by ECM stiffness also promote glucose uptake and aerobic glycolysis, and an altered metabolism is a recognized hallmark of cancer. Indeed, emerging evidence suggests that metabolic alterations and an abnormal ECM may cooperatively drive cancer cell aggression and treatment resistance. Accordingly, improved methods to monitor tissue mechanics and metabolism promise to improve diagnostics and treatments to ameliorate ECM stiffening and elevated mechanosignaling may improve patient outcome. Here we discuss the interplay between ECM mechanics and metabolism in tumor biology and suggest that monitoring these processes and targeting their regulatory pathways may improve diagnostics, therapy, and the prevention of malignant transformation. PMID:25532934

Bilateral transit time assessment of upper and lower limbs as a surrogate ankle brachial index marker.

PubMed

Foo, Jong Yong Abdiel

2008-01-01

Ankle brachial index is useful in monitoring the pathogenesis of peripheral arterial occlusive diseases. Sphygmomanometer is the standard instrument widely used but frequent prolonged monitoring can be less comfortable for patients. Pulse transit time is known to be inversely correlated with blood pressure and a ratio-based pulse transit time measurement has been proposed as a surrogate ankle brachial index marker. In this study, 17 normotensive adults (9 men; aged 25.4 +/- 3.9 years) were recruited. Two postural change test activities were performed to induce changes in the stiffness of the arterial wall of the moved periphery. Results showed that only readings from the limbs that adopted a new posture registered significant blood pressure and pulse transit time changes (P < .05). Furthermore, there was significant correlation between the ankle brachial index and pulse transit time ratio measure for both test activities (R(2) > or = 0.704). The findings herein suggest that pulse transit time ratio is a surrogate and accommodating ankle brachial index marker.

Measurements of the thermal neutron cross-section and resonance integral for the 108Pd(n,γ)109Pd reaction

NASA Astrophysics Data System (ADS)

Hien, Nguyen Thi; Kim, Guinyun; Kim, Kwangsoo; Do, Nguyen Van; Khue, Pham Duc; Thanh, Kim Tien; Shin, Sung-Gyun; Cho, Moo-Hyun

2018-06-01

The thermal neutron capture cross-section (σ0) and resonance integral (I0) of the 108Pd(n,γ)109Pd reaction have been measured relative to that of the monitor reaction 197Au(n,γ)198Au. The measurements were carried out using the neutron activation with the cadmium ratio method. Both the samples and monitors were irradiated with and without cadmium cover of 0.5 mm thickness. The induced activities of the reaction products were measured with a well calibrated HPGe γ-ray detector. In order to improve the accuracy of the results, the necessary corrections for the counting losses were made. The thermal neutron capture cross-section and resonance integral of the 108Pd(n,γ)109Pd reaction were determined to be σ0,Pd = 8.68 ± 0.41 barn and I0,Pd = 245.6 ± 24.8 barn, respectively. The obtained results are compared with literature values and discussed.

A review of citizen science and community-based environmental monitoring: issues and opportunities.

PubMed

Conrad, Cathy C; Hilchey, Krista G

2011-05-01

Worldwide, decision-makers and nongovernment organizations are increasing their use of citizen volunteers to enhance their ability to monitor and manage natural resources, track species at risk, and conserve protected areas. We reviewed the last 10 years of relevant citizen science literature for areas of consensus, divergence, and knowledge gaps. Different community-based monitoring (CBM) activities and governance structures were examined and contrasted. Literature was examined for evidence of common benefits, challenges, and recommendations for successful citizen science. Two major gaps were identified: (1) a need to compare and contrast the success (and the situations that induce success) of CBM programs which present sound evidence of citizen scientists influencing positive environmental changes in the local ecosystems they monitor and (2) more case studies showing use of CBM data by decision-makers or the barriers to linkages and how these might be overcome. If new research focuses on these gaps, and on the differences of opinions that exist, we will have a much better understanding of the social, economic, and ecological benefits of citizen science.

Reduction of oxidative-nitrosative stress underlies anticataract effect of topically applied tocotrienol in streptozotocin-induced diabetic rats

PubMed Central

Abdul Nasir, Nurul Alimah; Agarwal, Renu; Sheikh Abdul Kadir, Siti Hamimah; Vasudevan, Sushil; Tripathy, Minaketan; Iezhitsa, Igor; Mohammad Daher, Aqil; Ibrahim, Mohd Ikraam; Mohd Ismail, Nafeeza

2017-01-01

Cataract, a leading cause of blindness, is of special concern in diabetics as it occurs at earlier onset. Polyol accumulation and increased oxidative-nitrosative stress in cataractogenesis are associated with NFκB activation, iNOS expression, ATP depletion, loss of ATPase functions, calpain activation and proteolysis of soluble to insoluble proteins. Tocotrienol was previously shown to reduce lens oxidative stress and inhibit cataractogenesis in galactose-fed rats. In current study, we investigated anticataract effects of topical tocotrienol and possible mechanisms involved in streptozotocin-induced diabetic rats. Diabetes was induced in Sprague Dawley rats by intraperitoneal injection of streptozotocin. Diabetic rats were treated with vehicle (DV) or tocotrienol (DT). A third group consists of normal, non-diabetic rats were treated with vehicle (NV). All treatments were given topically, bilaterally, twice daily for 8 weeks with weekly slit lamp monitoring. Subsequently, rats were euthanized and lenses were subjected to estimation of polyol accumulation, oxidative-nitrosative stress, NFκB activation, iNOS expression, ATP levels, ATPase activities, calpain activity and total protein levels. Cataract progression was delayed from the fifth week onwards in DT with lower mean of cataract stages compared to DV group (p<0.01) despite persistent hyperglycemia. Reduced cataractogenesis in DT group was accompanied with lower aldose reductase activity and sorbitol level compared to DV group (p<0.01). DT group also showed reduced NFκB activation, lower iNOS expression and reduced oxidative-nitrosative stress compared to DV group. Lenticular ATP and ATPase and calpain 2 activities in DT group were restored to normal. Consequently, soluble to insoluble protein ratio in DT group was higher compared to DV (p<0.05). In conclusion, preventive effect of topical tocotrienol on development of cataract in STZ-induced diabetic rats could be attributed to reduced lens aldose reductase activity, polyol levels and oxidative-nitrosative stress. These effects of tocotrienol invlove reduced NFκB activation, lower iNOS expression, restoration of ATP level, ATPase activities, calpain activity and lens protein levels. PMID:28350848

Reduction of oxidative-nitrosative stress underlies anticataract effect of topically applied tocotrienol in streptozotocin-induced diabetic rats.

PubMed

Abdul Nasir, Nurul Alimah; Agarwal, Renu; Sheikh Abdul Kadir, Siti Hamimah; Vasudevan, Sushil; Tripathy, Minaketan; Iezhitsa, Igor; Mohammad Daher, Aqil; Ibrahim, Mohd Ikraam; Mohd Ismail, Nafeeza

2017-01-01

Cataract, a leading cause of blindness, is of special concern in diabetics as it occurs at earlier onset. Polyol accumulation and increased oxidative-nitrosative stress in cataractogenesis are associated with NFκB activation, iNOS expression, ATP depletion, loss of ATPase functions, calpain activation and proteolysis of soluble to insoluble proteins. Tocotrienol was previously shown to reduce lens oxidative stress and inhibit cataractogenesis in galactose-fed rats. In current study, we investigated anticataract effects of topical tocotrienol and possible mechanisms involved in streptozotocin-induced diabetic rats. Diabetes was induced in Sprague Dawley rats by intraperitoneal injection of streptozotocin. Diabetic rats were treated with vehicle (DV) or tocotrienol (DT). A third group consists of normal, non-diabetic rats were treated with vehicle (NV). All treatments were given topically, bilaterally, twice daily for 8 weeks with weekly slit lamp monitoring. Subsequently, rats were euthanized and lenses were subjected to estimation of polyol accumulation, oxidative-nitrosative stress, NFκB activation, iNOS expression, ATP levels, ATPase activities, calpain activity and total protein levels. Cataract progression was delayed from the fifth week onwards in DT with lower mean of cataract stages compared to DV group (p<0.01) despite persistent hyperglycemia. Reduced cataractogenesis in DT group was accompanied with lower aldose reductase activity and sorbitol level compared to DV group (p<0.01). DT group also showed reduced NFκB activation, lower iNOS expression and reduced oxidative-nitrosative stress compared to DV group. Lenticular ATP and ATPase and calpain 2 activities in DT group were restored to normal. Consequently, soluble to insoluble protein ratio in DT group was higher compared to DV (p<0.05). In conclusion, preventive effect of topical tocotrienol on development of cataract in STZ-induced diabetic rats could be attributed to reduced lens aldose reductase activity, polyol levels and oxidative-nitrosative stress. These effects of tocotrienol invlove reduced NFκB activation, lower iNOS expression, restoration of ATP level, ATPase activities, calpain activity and lens protein levels.

Single-cell imaging of the heat-shock response in colon cancer cells suggests that magnitude and length rather than time of onset determines resistance to apoptosis.

PubMed

Ramapathiran, Lavanya; Bernas, Tytus; Walter, Franziska; Williams, Linda; Düssmann, Heiko; Concannon, Caoimhín G; Prehn, Jochen H M

2014-02-01

Targeting the proteasome is a valuable approach for cancer therapy, potentially limited by pro-survival pathways that are induced in parallel to cell death. Whether these pro-survival pathways are activated in all cells, show different activation kinetics in sensitive versus resistant cells or interact functionally with cell death pathways is unknown. We monitored activation of the heat-shock response (HSR), a key survival pathway induced by proteasome inhibition, relative to apoptosis activation in HCT116 colon cancer cells expressing enhanced green fluorescent protein (EGFP) under the control of the HSP70 promoter. Single-cell and high-content time-lapse imaging of epoxomicin treatment revealed that neither basal activity nor the time of onset of the HSR differed between resistant and sensitive populations. However, resistant cells had significantly higher and prolonged reporter activity than those that succumbed to cell death. p53 deficiency protected against cell death but failed to modulate the HSR. By contrast, inhibition of the HSR significantly increased the cytotoxicity of epoxomicin. Our data provide novel insights into the kinetics and heterogeneity of the HSR during proteasome inhibition, suggesting that the HSR modulates cell death signalling unidirectionally.

Assessing NLRP3 Inflammasome Activation by Nanoparticles.

PubMed

Sharma, Bhawna; McLeland, Christopher B; Potter, Timothy M; Stern, Stephan T; Adiseshaiah, Pavan P

2018-01-01

NLRP3 inflammasome activation is one of the initial steps in an inflammatory cascade against pathogen/danger-associated molecular patterns (PAMPs/DAMPs), such as those arising from environmental toxins or nanoparticles, and is essential for innate immune response. NLRP3 inflammasome activation in cells can lead to the release of IL-1β cytokine via caspase-1, which is required for inflammatory-induced programmed cell death (pyroptosis). Nanoparticles are commonly used as vaccine adjuvants and drug delivery vehicles to improve the efficacy and reduce the toxicity of chemotherapeutic agents. Several studies indicate that different nanoparticles (e.g., liposomes, polymer-based nanoparticles) can induce NLRP3 inflammasome activation. Generation of a pro-inflammatory response is beneficial for vaccine delivery to provide adaptive immunity, a necessary step for successful vaccination. However, similar immune responses for intravenously injected, drug-containing nanoparticles can result in immunotoxicity (e.g., silica nanoparticles). Evaluation of NLRP3-mediated inflammasome activation by nanoparticles may predict pro-inflammatory responses in order to determine if these effects may be mitigated for drug delivery or optimized for vaccine development. In this protocol, we outline steps to monitor the release of IL-1β using PMA-primed THP-1 cells, a human monocytic leukemia cell line, as a model system. IL-1β release is used as a marker of NLRP3 inflammasome activation.

Physical activity and epilepsy: proven and predicted benefits.

PubMed

Arida, Ricardo M; Cavalheiro, Esper A; da Silva, Antonio C; Scorza, Fulvio A

2008-01-01

Epilepsy is a common disease found in 2% of the population, affecting people from all ages. Unfortunately, persons with epilepsy have previously been discouraged from participation in physical activity and sports for fear of inducing seizures or increasing seizure frequency. Despite a shift in medical recommendations toward encouraging rather than restricting participation, the stigma remains and persons with epilepsy continue to be less active than the general population. For this purpose, clinical and experimental studies have analysed the effect of physical exercise on epilepsy. Although there are rare cases of exercise-induced seizures, studies have shown that physical activity can decrease seizure frequency, as well as lead to improved cardiovascular and psychological health in people with epilepsy. The majority of physical activities or sports are safe for people with epilepsy to participate in with special attention to adequate seizure control, close monitoring of medications, and preparation of family or trainers. The evidence shows that patients with good seizure control can participate in both contact and non-contact sports without harmfully affecting seizure frequency. This article reviews the risks and benefits of physical activity in people with epilepsy, discusses sports in which persons with epilepsy may participate, and describes the positive effect of physical exercise in experimental models of epilepsy.

Construction of mutant TKGFP for real-time imaging of temporal dynamics of HIF-1 signal transduction activity mediated by hypoxia and reoxygenation in tumors in living mice.

PubMed

Hsieh, Chia-Hung; Kuo, Jung-Wen; Lee, Yi-Jang; Chang, Chi-Wei; Gelovani, Juri G; Liu, Ren-Shyan

2009-12-01

The herpes simplex virus type 1 thymidine kinase (HSV1-tk)/green fluorescent protein (TKGFP) dual-reporter gene and a multimodality imaging approach play a critical role in monitoring therapeutic gene expression, immune cell trafficking, and protein-protein interactions in translational molecular-genetic imaging. However, the cytotoxicity and low temporal resolution of TKGFP limits its application in studies that require a rapid turnover of the reporter. The purpose of this study was to construct a novel mutant TKGFP fusion reporter gene with low cytotoxicity and high temporal resolution for use in the real-time monitoring of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor 1 (HIF-1) signal transduction activity mediated by hypoxia and reoxygenation in vitro and in vivo. Destabilized TKGFP was produced by inserting the nuclear export signal (NES) sequence at the N terminus and fusing the degradation domain of mouse ornithine decarboxylase (dMODC) at the C terminus. The stability of TKGFP in living NG4TL4 cells was determined by Western blot analysis, HSV1-tk enzyme activity assay, and flow cytometric analysis. The suitability of NESTKGFP:dMODC as a transcription reporter was investigated by linking it to a promoter consisting of 8 copies of hypoxia-responsive elements, whose activities depend on HIF-1. The dynamic transcriptional events mediated by hypoxia and reoxygenation were monitored by NESTKGFP:dMODC or TKGFP and determined by optical imaging and PET. Unlike TKGFP, NESTKGFP:dMODC was unstable in the presence of cycloheximide and showed a short half-life of protein and enzyme activity. Rapid turnover of NESTKGFP:dMODC occurred in a 26S proteasome-dependent manner. Furthermore, NESTKGFP:dMODC showed an upregulated expression and low cytotoxicity in living cells. Studies of hypoxia-responsive TKGFP and NESTKGFP:dMODC expression showed that NESTKGFP:dMODC as a reporter gene had better temporal resolution than did TKGFP for monitoring the dynamic transcriptional events mediated by hypoxia and reoxygenation; the TKGFP expression level was not optimal for the purpose of monitoring. In translational molecular-genetic imaging, NESTKGFP:dMODC as a reporter gene, together with optical imaging and PET, allows the direct monitoring of transcription induction and easy determination of its association with other biochemical changes.

Palmar skin conductance variability and the relation to stimulation, pain and the motor activity assessment scale in intensive care unit patients

PubMed Central

2013-01-01

Introduction Many intensive care unit (ICU) patients describe pain and other adverse feelings that may impact long-term psychological morbidity. Sympathetically mediated palmar skin conductance variability is related to emotionally induced perspiration and correlates with pain levels in the perioperative setting but has not been studied in ICU patients. Methods Twenty non-intubated and 20 intubated general ICU patients were included in this observational study. Patients were monitored with the MED-STORM Pain Monitoring System®. The number of skin conductance fluctuations per second (NSCF) was measured in parallel with bedside observation during one hour of intensive care, including rest, procedures and patient-staff interactions. Arousal-agitation level was monitored with the motor activity assessment scale (MAAS). Pain was monitored with the numeric rating scale (0 to 10) in patients able to communicate or by observation in patients unable to communicate. Results In non-intubated patients, NSCF increased with increasing stimulation/pain but also with higher MAAS (P = 0.002). An interaction effect was found, with increased NSCF response to stimulation/pain with increasing MAAS (P < 0.001). In intubated patients, NSCF increased significantly with increasing stimulation/pain (P < 0.001). In contrast to non-intubated patients, no difference in NSCF between MAAS levels was found for any given degree of stimulation in intubated patients. Conclusions In critically ill patients, NSCF may be more useful evaluating emotional distress rather than pain alone. It needs to be assessed whether NSCF monitoring is clinically useful and whether controlling emotional distress with the aid of such monitoring may impact on patient care and outcomes. PMID:23510014

Bad is not involved in DHA-induced apoptosis in human lung adenocarcinoma ASTC-a-1 cells

NASA Astrophysics Data System (ADS)

Yu, Huai-na; Lu, Ying-ying; Chen, Tong-sheng

2011-03-01

Dihydroartemisinin (DHA), a first-line anti-malarial drug with low toxicity, has been shown to possess promising anticancer activities and induce cancer cell death through apoptotic pathway, but the molecular mechanisms are not well understood. In this paper, we focus on whether Bad, a BH3-only pro-apoptotic protein, is involved in apoptotic cell death in DHA-treated human lung adenocarcinoma (ASTC-a-1) cells. Confocal fluorescence microscope imaging was used to monitor the temporal and spatial distribution of Bad in single living cells. Our results indicate that Bad is still located in cytoplasm and does not translocate to mitochondria after treatment with DHA for 24 h, while only a small proportion of Bad located in cytoplasm in the STS-treated cells for 6 h. These results show for the first time that Bad is not involved in DHA-induced apoptosis in ASTC-a-1 cells, which could give more evidence for the molecular mechanisms of apoptosis induced by DHA.

Activation of PPARbeta/delta induces endothelial cell proliferation and angiogenesis.

PubMed

Piqueras, Laura; Reynolds, Andrew R; Hodivala-Dilke, Kairbaan M; Alfranca, Arántzazu; Redondo, Juan M; Hatae, Toshihisa; Tanabe, Tadashi; Warner, Timothy D; Bishop-Bailey, David

2007-01-01

The role of the nuclear receptor peroxisome-proliferator activated receptor (PPAR)-beta/delta in endothelial cells remains unclear. Interestingly, the selective PPARbeta/delta ligand GW501516 is in phase II clinical trials for dyslipidemia. Here, using GW501516, we have assessed the involvement of PPARbeta/delta in endothelial cell proliferation and angiogenesis. Western blot analysis indicated PPARbeta/delta was expressed in primary human umbilical and aortic endothelial cells, and in the endothelial cell line, EAHy926. Treatment with GW501516 increased human endothelial cell proliferation and morphogenesis in cultures in vitro, endothelial cell outgrowth from murine aortic vessels in vitro, and angiogenesis in a murine matrigel plug assay in vivo. GW501516 induced vascular endothelial cell growth factor mRNA and peptide release, as well as adipose differentiation-related protein (ADRP), a PPARbeta/delta target gene. GW501516-induced proliferation, morphogenesis, vascular endothelial growth factor (VEGF), and ADRP were absent in endothelial cells transfected with dominant-negative PPARbeta/delta. Furthermore, treatment of cells with cyclo-VEGFI, a VEGF receptor1/2 antagonist, abolished GW501516-induced endothelial cell proliferation and tube formation. PPARbeta/delta is a novel regulator of endothelial cell proliferation and angiogenesis through VEGF. The use of GW501516 to treat dyslipidemia may need to be carefully monitored in patients susceptible to angiogenic disorders.

Laser-shocked energetic materials with metal additives: evaluation of chemistry and detonation performance.

PubMed

Gottfried, Jennifer L; Bukowski, Eric J

2017-01-20

A focused, nanosecond-pulsed laser has been used to ablate, atomize, ionize, and excite milligram quantities of metal-doped energetic materials that undergo exothermic reactions in the laser-induced plasma. The subsequent shock wave expansion in the air above the sample has been monitored using high-speed schlieren imaging in a recently developed technique, laser-induced air shock from energetic materials (LASEM). The method enables the estimation of detonation velocities based on the measured laser-induced air-shock velocities and has previously been demonstrated for organic military explosives. Here, the LASEM technique has been extended to explosive formulations with metal additives. A comparison of the measured laser-induced air-shock velocities for TNT, RDX, DNTF, and LLM-172 doped with Al or B to the detonation velocities predicted by the thermochemical code CHEETAH for inert or active metal participation demonstrates that LASEM has potential for predicting the early time (<10  μs) participation of metal additives in detonation events. The LASEM results show that while Al is mostly inert at early times in the detonation event (confirmed from large-scale detonation testing), B is active-and reducing the amount of hydrogen present during the early chemical reactions increases the resulting estimated detonation velocities.

Monitoring apoptosis of TK-GFP-expressing ACC-M cells induced by ACV using FRET technique

NASA Astrophysics Data System (ADS)

Xiong, Tao; Zhang, Zhihong; Lin, Juqiang; Yang, Jie; Zeng, Shaoqun; Luo, Qingming

2006-05-01

Apoptosis is an evolutionary conserved cellular process that plays an important role during development, but it is also involved in tissue homeostasis and in many diseases. To study the characteristics of suicide gene system of the herpes simplex virus thymidine kinase (HSV-tk) gene in tumor cells and explore the apoptosis phenomena in this system and its effect on the human adenoid cystic carcinoma line ACC-M cell, we detected apoptosis of CD3- (ECFP-CRS-DsRed) and TK-GFP-expressing ACC-M (ACC-M-TK-GFP-CD3) cells induced by acyclovir (ACV) using fluorescence resonance energy transfer (FRET) technique. CD3 is a FRET-based indicator for activity of caspase-3, which is composed of an enhanced cyan fluorescent protein, a caspase-3 sensitive linker, and a red fluorescent protein from Discosoma with efficient maturation property. FRET from ECFP to DsRed could be detected in normal ACC-M-TK-GFP-CD3 cells, and the FRET efficient was remarkably decreased and then disappeared during the cells apoptosis induced by ACV. It was due to the activated caspase-3 cleaved the CD3 fusion protein. In this study, the results suggested that the ACV-induced apoptosis of ACC-M-TK-GFP-CD3 cells was through caspase-3 pathway.

Monitoring apoptosis of TK-GFP-expressing ACC-M cells induced by ACV using FRET technique

NASA Astrophysics Data System (ADS)

Xiong, Tao; Zhang, Zhihong; Lin, Juqiang; Yang, Jie; Zeng, Shaoqun; Luo, Qingming

2006-09-01

Apoptosis is an evolutionary conserved cellular process that plays an important role during development, but it is also involved in tissue homeostasis and in many diseases. To study the characteristics of suicide gene system of the herpes simplex virus thymidine kinase (HSV-tk) gene in tumor cells and explore the apoptosis phenomena in this system and its effect on the human adenoid cystic carcinoma line ACC-M cell, we detected apoptosis of CD3- (ECFP-CRS-DsRed) and TK-GFP-expressing ACC-M (ACC-M-TK-GFP-CD3) cells induced by acyclovir (ACV) using fluorescence resonance energy transfer (FRET) technique. CD3 is a FRET-based indicator for activity of caspase-3, which is composed of an enhanced cyan fluorescent protein, a caspase-3 sensitive linker, and a red fluorescent protein from Discosoma with efficient maturation property. FRET from ECFP to DsRed could be detected in normal ACC-M-TK-GFP-CD3 cells, and the FRET efficient was remarkably decreased and then disappeared during the cells apoptosis induced by ACV. It was due to the activated caspase-3 cleaved the CD3 fusion protein. In this study, the results suggested that the AVC-induced apoptosis of ACC-M-TK-GFP-CD3 cells was through caspase-3 pathway.

Nitrosative stress mediated misfolded protein aggregation mitigated by Na-D-{beta}-hydroxybutyrate intervention

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kabiraj, Parijat; Pal, Rituraj; Varela-Ramirez, Armando

2012-09-28

Highlights: Black-Right-Pointing-Pointer Rotenone is a model for inducing apoptosis and synphilin-1 accumulation in Parkinson Prime s studies. Black-Right-Pointing-Pointer The metabolite sodium betahydroxybutryate mitigates these effects in SHSY5Y cell lines. Black-Right-Pointing-Pointer Results reveal a novel and innate mechanism to prevent neurodegeneration/cell death. -- Abstract: Mitochondrial dysfunction, leading to elevated levels of reactive oxygen species, is associated with the pathogenesis of neurodegenerative disorders. Rotenone, a mitochondrial stressor induces caspase-9 and caspase-3 activation leading proteolytic cleavage of substrate nuclear poly(ADP-ribose) polymerase (PARP). PARP cleavage is directly related to apoptotic cell death. In this study, we have monitored the aggregation of green-fluorescent protein (GFP)-taggedmore » synphilin-1, as a rotenone-induced Parkinsonia-onset biomarker. We report that the innate ketone body, Na-D-{beta}-hydroxybutyrate (Na{beta}HB) reduces markedly the incidence of synphilin-1 aggregation. Furthermore, our data reveal that the metabolic byproduct also prevents rotenone-induced caspase-activated apoptotic cell death in dopaminergic SH-SY5Y cells. Together, these results suggest that Na{beta}HB is neuroprotective; it attenuates effects originating from mitochondrial insult and can serve as a scaffold for the design and development of sporadic neuropathies.« less

Coffee mitigates cyclophosphamide-induced genotoxic damage in Drosophila melanogaster germ cells.

PubMed

Nagpal, Isha; Abraham, Suresh K

2018-02-26

In the present study, coffee (CF) was evaluated for its protective effects against genotoxic damage and oxidative stress induced by the chemotherapeutic drug, cyclophosphamide (CPH). The sex-linked recessive lethal (SLRL) test was employed to study the induction of mutations in the larvae as well as in all the successive germ cell stages of treated males. Control and treated third instar larvae were used to monitor the biomarkers of oxidative stress response such as glutathione content (GSH), glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD) and lipid peroxidation (MDA content). Our results demonstrated that co-administration of CF (2%) with CPH (3 mM) has significantly reduced CPH-induced lethal mutations in the germ cells of larvae and adult flies. The reductions observed in mutation frequencies were: 75% in larvae and 62.4% in the adult. Significant enhancement in antioxidant enzymatic levels: CAT (46.6%) > SOD (43.0%) > GST (42.4%) > GSH (31.6%) and reduction in MDA levels (32.05%) in the pretreated third instar larvae demonstrated the antioxidant activity of CF against CPH-induced oxidative stress. The findings from the present study suggest that the Drosophila model is an ideal one for evaluating the antigenotoxic and antioxidant activity of complex mixtures like CF.

Evaluation of the antipsychotic potential of Panax quinquefolium in ketamine induced experimental psychosis model in mice.

PubMed

Chatterjee, Manavi; Singh, Seema; Kumari, Reena; Verma, Anil Kumar; Palit, Gautam

2012-04-01

The search for novel pharmacotherapy from medicinal plants for psychiatric illnesses has progressed significantly from the past few decades and their therapeutic potential has been assessed in a variety of animal models. The aim of our study was to screen one such plant, Panax quinquefolium (PQ), with significant neuroactive properties for its antipsychotic potential. A graded dose study with PQ at 12.5-200 mg/kg, p. o. showed differential effects against the ketamine induced hyperactivity in the Digiscan animal activity monitor. Nevertheless at 100 mg/kg, p.o., PQ blocked ketamine induced memory impairment in the passive avoidance paradigm. In the chronic studies, PQ reduced the ketamine induced enhanced immobility in the forced swim test and did not show extra-pyramidal side effects in bar test and wood block test of catalepsy. These behavioural effects were compared with standard drugs haloperidol and clozapine. Further PQ reduced DA and 5-HT content after chronic treatment, but not after acute administration. In addition, PQ extract reduced acetylcholinesterase activity and nitrate levels, however increased glutamate levels in hippocampus. Overall our findings suggest that PQ possess antipsychotic like properties, which may leads to future studies with its specific constituents which may particularly be beneficial in predominant negative and cognitive symptoms of schizophrenia.

Inhibition of Nogo-B promotes cardiac hypertrophy via endoplasmic reticulum stress.

PubMed

Li, Junli; Wu, Wenchao; Xin, Yanguo; Zhao, Mingyue; Liu, Xiaojing

2018-05-14

Nogo-B is a key endoplasmic reticulum (ER) protein that regulates ER stress signaling. However, its role in cardiac hypertrophy remains poorly understood. ER stress is interrelated with autophagy in the process of cardiac hypertrophy. Therefore, we aimed to test the hypothesis that both ER stress and autophagy signaling mediate the function of Nogo-B in cardiac hypertrophy. Rat models of transverse aortic constriction (TAC), neonatal rat cardiomyocytes (NRCMs) stimulated with norepinephrine (Ne) and primary cardiac fibroblasts treated with transforming growth factor β1 (TGF-β1) were used in this study. The expression of Nogo-B and markers of ER stress were determined by quantitative RT-PCR, western blotting and immunofluorescence. Autophagy was measured by monitoring autophagic flux. Specific small interfering RNA (siRNA) of Nogo-B was transfected to investigate the role of Nogo-B in regulating cardiac hypertrophy. In TAC-induced hypertrophic heart tissues, Ne-treated hypertrophic cardiomyocytes and TGF-β1-stimulated cardiac fibroblasts, the expression of Nogo-B, and markers of ER stress were significantly elevated. Impairment of autophagic flux was observed in the activated cardiac fibroblasts. Down-regulation of Nogo-B by siRNA further exacerbated Ne-induced cardiomyocyte hypertrophy and TGF-β1-induced cardiac fibroblast activation. Gene silencing of Nogo-B promoted the activation of the ER stress pathway and the impairment of autophagic flux. Moreover, inhibition of Nogo-B activated the protein kinase RNA-like ER kinase (PERK)/activating transcriptional factor 4 (ATF4) and activating transcriptional factor 6 (ATF6) branches of ER stress pathways. These findings suggest that inhibition of Nogo-B promotes cardiomyocyte hypertrophy and cardiac fibroblast activation by activating the PERK/ATF4 signaling pathway and defects of autophagic flux. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Calpains are downstream effectors of bax-dependent excitotoxic apoptosis.

PubMed

D'Orsi, Beatrice; Bonner, Helena; Tuffy, Liam P; Düssmann, Heiko; Woods, Ina; Courtney, Michael J; Ward, Manus W; Prehn, Jochen H M

2012-02-01

Excitotoxicity resulting from excessive Ca(2+) influx through glutamate receptors contributes to neuronal injury after stroke, trauma, and seizures. Increased cytosolic Ca(2+) levels activate a family of calcium-dependent proteases with papain-like activity, the calpains. Here we investigated the role of calpain activation during NMDA-induced excitotoxic injury in embryonic (E16-E18) murine cortical neurons that (1) underwent excitotoxic necrosis, characterized by immediate deregulation of Ca(2+) homeostasis, a persistent depolarization of mitochondrial membrane potential (Δψ(m)), and insensitivity to bax-gene deletion, (2) underwent excitotoxic apoptosis, characterized by recovery of NMDA-induced cytosolic Ca(2+) increases, sensitivity to bax gene deletion, and delayed Δψ(m) depolarization and Ca(2+) deregulation, or (3) that were tolerant to excitotoxic injury. Interestingly, treatment with the calpain inhibitor calpeptin, overexpression of the endogenous calpain inhibitor calpastatin, or gene silencing of calpain protected neurons against excitotoxic apoptosis but did not influence excitotoxic necrosis. Calpeptin failed to exert a protective effect in bax-deficient neurons but protected bid-deficient neurons similarly to wild-type cells. To identify when calpains became activated during excitotoxic apoptosis, we monitored calpain activation dynamics by time-lapse fluorescence microscopy using a calpain-sensitive Förster resonance energy transfer probe. We observed a delayed calpain activation that occurred downstream of mitochondrial engagement and directly preceded neuronal death. In contrast, we could not detect significant calpain activity during excitotoxic necrosis or in neurons that were tolerant to excitotoxic injury. Oxygen/glucose deprivation-induced injury in organotypic hippocampal slice cultures confirmed that calpains were specifically activated during bax-dependent apoptosis and in this setting function as downstream cell-death executioners.

Acute stress shifts the balance between controlled and automatic processes in prospective memory.

PubMed

Möschl, Marcus; Walser, Moritz; Plessow, Franziska; Goschke, Thomas; Fischer, Rico

2017-10-01

In everyday life we frequently rely on our abilities to postpone intentions until later occasions (prospective memory; PM) and to deactivate completed intentions even in stressful situations. Yet, little is known about the effects of acute stress on these abilities. In the present work we investigated the impact of acute stress on PM functioning under high task demands. (1) Different from previous studies, in which intention deactivation required mostly low processing demands, we used salient focal PM cues to induce high processing demands during intention-deactivation phases. (2) We systematically manipulated PM-monitoring demands in a nonfocal PM task that required participants to monitor for either one or six specific syllables that could occur in ongoing-task words. Eighty participants underwent the Trier Social Stress Test, a standardized stress induction protocol, or a standardized control situation, before performing a computerized PM task. Our primary interests were whether PM performance, PM-monitoring costs, aftereffects of completed intentions and/or commission-error risk would differ between stressed and non-stressed individuals and whether these effects would differ under varying task demands. Results revealed that PM performance and aftereffects of completed intentions during subsequent performance were not affected by acute stress induction, replicating previous findings. Under high demands on intention deactivation (focal condition), however, acute stress produced a nominal increase in erroneous PM responses after intention completion (commission errors). Most importantly, under high demands on PM monitoring (nonfocal condition), acute stress led to a substantial reduction in PM-monitoring costs. These findings support ideas of selective and demand-dependent effects of acute stress on cognitive functioning. Under high task demands, acute stress might induce a shift in processing strategy towards resource-saving behavior, which seems to increase the efficiency of PM performance (reduced monitoring costs), but might increase initial susceptibility to automatic response activation after intention completion. Copyright © 2017 Elsevier Inc. All rights reserved.

A new venous infusion path monitoring system utilizing electrostatic induced potential.

PubMed

Ogawa, Hidekuni; Yonezawa, Yoshiharu; Maki, Hiromichi; Caldwell, W Morton

2008-01-01

A new venous infusion pathway monitoring system has been developed for hospital and home use. The system consists of linear and digital integrated circuits and a low-power 8-bit single chip microcomputer which constantly monitors the infusion pathway intactness. A 330 kHz AC voltage, which is induced on the patient's body by electrostatic coupling from a 330 kHz pulse oscillator, can be recorded by main and reference electrodes wrapped around the infusion polyvinyl chloride tube. If the injection needle or infusion tube becomes detached, then the system detects changes in the induced AC voltages and alerts the nursing station, via the nurse call system or PHS (personal handy phone system).

Vitamin D protects keratinocytes from deleterious effects of ionizing radiation.

PubMed

Langberg, M; Rotem, C; Fenig, E; Koren, R; Ravid, A

2009-01-01

Radiotherapy can induce severe skin responses that may limit the clinically acceptable radiation dose. The responses include erythema, dry and moist desquamation, erosions and dermal-epidermal blister formation. These effects reflect injury to, and reproductive failure of, epidermal cells and may also be due to dysregulation of the tissue remodelling process caused by excessive proteolytic activity. Calcitriol, the hormonally active vitamin D metabolite, protects keratinocytes from programmed cell death induced by various noxious stimuli. To examine whether calcitriol protects proliferating keratinocytes from the damage inflicted by ionizing radiation under conditions similar to those employed during radiotherapy. Autonomously proliferating HaCaT keratinocytes, used as a model for basal layer keratinocytes, were irradiated using a linear accelerator. Cell death was monitored by vital staining, executioner caspase activation, lactic dehydrogenase release and colony formation assay. Induction of matrix metalloproteinase-9 was assessed by gelatinase activity assay and mRNA determination. Levels of specific proteins were determined by immunoblotting. Treatment with calcitriol inhibited both caspase-dependent and -independent programmed cell death occurring within 48 h of irradiation and increased the colony formation capacity of irradiated cells. These effects may be attributable to inhibition of the c-Jun NH(2)-terminal kinase cascade and to upregulation of the truncated antiapoptotic isoform of p63. Treatment with the hormone also attenuated radiation-induced increase in matrix metalloproteinase-9 protein and mRNA levels. The results of this study suggest that active vitamin D derivatives may attenuate cell death and excessive proteolytic activity in the epidermis due to exposure to ionizing radiation in the course of radiotherapy.

A cellular mechanism for dendritic spine loss in the pilocarpine model of status epilepticus.

PubMed

Kurz, Jonathan E; Moore, Bryan J; Henderson, Scott C; Campbell, John N; Churn, Severn B

2008-10-01

Previous studies have documented a synaptic translocation of calcineurin (CaN) and increased CaN activity following status epilepticus (SE); however, the cellular effect of these changes in CaN in the pathology of SE remains to be elucidated. This study examined a CaN-dependent modification of the dendritic cytoskeleton. CaN has been shown to induce dephosphorylation of cofilin, an actin depolymerization factor. The ensuing actin depolymerization can lead to a number of physiological changes that are of interest in SE. SE was induced by pilocarpine injection, and seizure activity was monitored by video-EEG. Subcellular fractions were isolated by differential centrifugation. CaN activity was assayed using a paranitrophenol phosphate (pNPP) assay protocol. Cofilin phosphorylation was assessed using phosphocofilin-specific antibodies. Cofilin-actin binding was determined by coimmunoprecipitation, and actin polymerization was measured using a triton-solubilization protocol. Spines were visualized using a single-section rapid Golgi impregnation procedure. The immunoreactivity of phosphocofilin decreased significantly in hippocampal and cortical synaptosomal samples after SE. SE-induced cofilin dephosphorylation could be partially blocked by the preinjection of CaN inhibitors. Cofilin activation could be further demonstrated by increased actin-cofilin binding and a significant depolymerization of neuronal actin, both of which were also blocked by CaN inhibitors. Finally, we demonstrated a CaN-dependent loss of dendritic spines histologically. The data demonstrate a CaN-dependent, cellular mechanism through which prolonged seizure activity results in loss of dendritic spines via cofilin activation. Further research into this area may provide useful insights into the pathology of SE and epileptogenic mechanisms.

Picomolar platelet-activating factor mobilizes Ca to change platelet shape without activating phospholipase C or protein kinase C; simultaneous fluorometric measurement of intracellular free Ca concentration and aggregation.

PubMed

James-Kracke, M R; Sexe, R B; Shukla, S D

1994-11-01

The purpose of this study was to investigate signal transduction mechanisms activated by low and high concentrations of platelet-activating factor (PAF) in rabbit platelets and to contrast the responses to those induced by thrombin. We measured changes in intracellular free calcium ([Ca++]i) with fura2, while monitoring light scatter simultaneously as a measure of shape change and aggregation in a dual-excitation dual-emission spectrofluorometer. An abrupt 20% fall in light scatter, coincident with the peak of the [Ca++]i, indicated shape change in Ca-containing or Ca-free medium and was blocked by BAPTA loading and 10 microM cytochalasin B. A secondary decline in light scatter, indicating aggregation, occurred only in Ca-containing medium and only under conditions favoring protein kinase C (PKC) activation. PAF at 10(-12) M did not increase 1,4,5-inositol triphosphate content, which suggested PKC would not be activated. However, PAF at 10(-12) rapidly increased [Ca++]i to 900 nM in 7 sec seemingly by Ca influx through receptor-operated channels inducing shape change. PAF at 10(-9) and 10(-8) M increased [Ca++]i to 2 microM in 12 sec and induced both shape change and aggregation. However, in platelets pretreated with 100 nM staurosporine to inhibit protein kinases, 10(-9) M PAF did not cause aggregation even though [Ca++]i still rose to 2 microM, which indicated that PKC plays a role in aggregation but not in Ca++ mobilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR(2) ) is involved in vascular function.

PubMed

Bucci, M; Vellecco, V; Harrington, L; Brancaleone, V; Roviezzo, F; Mattace Raso, G; Ianaro, A; Lungarella, G; De Palma, R; Meli, R; Cirino, G

2013-01-01

Proteinase-activated receptors (PARs) and toll-like receptors (TLRs) are involved in innate immune responses. The aim of this study was to evaluate the possible cross-talk between PAR(2) and TLR4 in vessels in physiological condition and how it varies following stimulation of TLR4 by using in vivo and ex vivo models. Thoracic aortas were harvested from both naïve and endotoxaemic rats for in vitro studies. Arterial blood pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4 agonist while PAR(2) activating peptide (AP) was used as a PAR(2) agonist. Aortas harvested from TLR4(-/-) mice were also used to characterize the PAR(2) response. PAR(2) , but not TLR4, expression was enhanced in aortas of endotoxaemic rats. PAR(2) AP-induced vasorelaxation was increased in aortic rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced PAR(2) AP-induced vasorelaxation and PAR(2) AP-induced hypotension in both naïve and endotoxaemic rats. Finally, in aortic rings from TLR4(-/-) mice, the expression of PAR(2) was reduced and the PAR(2) AP-induced vasodilatation impaired compared with those from wild-type mice and both resveratrol and curcumine were ineffective. Cross-talk between PAR(2) and TLR4 contributes to vascular homeostasis. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR2) is involved in vascular function

PubMed Central

Bucci, M; Vellecco, V; Harrington, L; Brancaleone, V; Roviezzo, F; Mattace Raso, G; Ianaro, A; Lungarella, G; De Palma, R; Meli, R; Cirino, G

2013-01-01

Background and Purpose Proteinase-activated receptors (PARs) and toll-like receptors (TLRs) are involved in innate immune responses. The aim of this study was to evaluate the possible cross-talk between PAR2 and TLR4 in vessels in physiological condition and how it varies following stimulation of TLR4 by using in vivo and ex vivo models. Experimental Approach Thoracic aortas were harvested from both naïve and endotoxaemic rats for in vitro studies. Arterial blood pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4 agonist while PAR2 activating peptide (AP) was used as a PAR2 agonist. Aortas harvested from TLR4–/– mice were also used to characterize the PAR2 response. Key Results PAR2, but not TLR4, expression was enhanced in aortas of endotoxaemic rats. PAR2AP-induced vasorelaxation was increased in aortic rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced PAR2AP-induced vasorelaxation and PAR2AP-induced hypotension in both naïve and endotoxaemic rats. Finally, in aortic rings from TLR4–/– mice, the expression of PAR2 was reduced and the PAR2AP-induced vasodilatation impaired compared with those from wild-type mice and both resveratrol and curcumine were ineffective. Conclusions and Implications Cross-talk between PAR2 and TLR4 contributes to vascular homeostasis. PMID:22957757

Evaluation of immune functions in captive immature loggerhead sea turtles (Caretta caretta).

PubMed

Rousselet, Estelle; Levin, Milton; Gebhard, Erika; Higgins, Benjamin M; DeGuise, Sylvain; Godard-Codding, Céline A J

2013-11-15

Sea turtles face numerous environmental challenges, such as exposure to chemical pollution and biotoxins, which may contribute to immune system impairment, resulting in increased disease susceptibility. Therefore, a more thorough assessment of the host's immune response and its susceptibility is needed for these threatened and endangered animals. In this study, the innate and acquired immune functions of sixty-five clinically healthy, immature, captive loggerhead sea turtles (Caretta caretta) were assayed using non-lethal blood sample collection. Functional immune assays were developed and/or optimized for this species, including mitogen-induced lymphocyte proliferation, natural killer (NK) cell activity, phagocytosis, and respiratory burst. Peripheral blood mononuclear cells (PBMC) and phagocytes were isolated by density gradient centrifugation on Ficoll-Paque and discontinuous Percoll gradients, respectively. The T lymphocyte mitogens ConA significantly induced lymphocyte proliferation at 1 and 2 μg/mL while PHA significantly induced lymphocyte proliferation at 5 and 10 μg/mL. The B lymphocyte mitogen LPS significantly induced proliferation at 1 μg/mL. Monocytes demonstrated higher phagocytic activity than eosinophils. In addition, monocytes exhibited respiratory burst. Natural killer cell activity was higher against YAC-1 than K-562 target cells. These optimized assays may help to evaluate the integrity of loggerhead sea turtle's immune system upon exposure to environmental contaminants, as well as part of a comprehensive health assessment and monitoring program. Copyright © 2013 Elsevier B.V. All rights reserved.

Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism.

PubMed

Matsuo, Kiyoshi; Ban, Ryokuya; Hama, Yuki; Yuzuriha, Shunsuke

2015-01-01

Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus.

Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism

PubMed Central

Matsuo, Kiyoshi; Ban, Ryokuya; Hama, Yuki; Yuzuriha, Shunsuke

2015-01-01

Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus. PMID:26244675

High Intensity Focused Ultrasound Monitoring using Harmonic Motion Imaging for Focused Ultrasound (HMIFU) under boiling or slow denaturation conditions

PubMed Central

Hou, Gary Y.; Marquet, Fabrice; Wang, Shutao; Apostolakis, Iason-Zacharias; Konofagou, Elisa E.

2015-01-01

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a recently developed High-Intensity Focused Ultrasound (HIFU) treatment monitoring method that utilizes an amplitude-modulated therapeutic ultrasound beam to induce an oscillatory radiation force at the HIFU focus and estimates the focal tissue displacement to monitor the HIFU thermal treatment. In this study, the performance of HMIFU under acoustic, thermal and mechanical effects were investigated. The performance of HMIFU was assessed in ex vivo canine liver specimens (n=13) under slow denaturation or boiling regimes. Passive Cavitation Detector (PCD) was used to assess the acoustic cavitation activity while a bare-wire thermocouple was used to monitor the focal temperature change. During lesioning with slow denaturation, high quality displacements (correlation coefficient above 0.97) were observed under minimum cavitation noise, indicating tissue the initial-softening-then-stiffening property change. During HIFU with boiling, HMIFU monitored a consistent change in lesion-to-background displacement contrast (0.46±0.37) despite the presence of strong cavitation noise due to boiling during lesion formation. Therefore, HMIFU effectively monitored softening-then-stiffening during lesioning under slow denaturation, and detected lesioning under boiling with a distinct change in displacement contrast under boiling in the presence of cavitation. In conclusion, HMIFU was shown effective in HIFU monitoring and lesioning identification without being significantly affected by cavitation noise. PMID:26168177

A brain-machine interface for control of medically-induced coma.

PubMed

Shanechi, Maryam M; Chemali, Jessica J; Liberman, Max; Solt, Ken; Brown, Emery N

2013-10-01

Medically-induced coma is a drug-induced state of profound brain inactivation and unconsciousness used to treat refractory intracranial hypertension and to manage treatment-resistant epilepsy. The state of coma is achieved by continually monitoring the patient's brain activity with an electroencephalogram (EEG) and manually titrating the anesthetic infusion rate to maintain a specified level of burst suppression, an EEG marker of profound brain inactivation in which bursts of electrical activity alternate with periods of quiescence or suppression. The medical coma is often required for several days. A more rational approach would be to implement a brain-machine interface (BMI) that monitors the EEG and adjusts the anesthetic infusion rate in real time to maintain the specified target level of burst suppression. We used a stochastic control framework to develop a BMI to control medically-induced coma in a rodent model. The BMI controlled an EEG-guided closed-loop infusion of the anesthetic propofol to maintain precisely specified dynamic target levels of burst suppression. We used as the control signal the burst suppression probability (BSP), the brain's instantaneous probability of being in the suppressed state. We characterized the EEG response to propofol using a two-dimensional linear compartment model and estimated the model parameters specific to each animal prior to initiating control. We derived a recursive Bayesian binary filter algorithm to compute the BSP from the EEG and controllers using a linear-quadratic-regulator and a model-predictive control strategy. Both controllers used the estimated BSP as feedback. The BMI accurately controlled burst suppression in individual rodents across dynamic target trajectories, and enabled prompt transitions between target levels while avoiding both undershoot and overshoot. The median performance error for the BMI was 3.6%, the median bias was -1.4% and the overall posterior probability of reliable control was 1 (95% Bayesian credibility interval of [0.87, 1.0]). A BMI can maintain reliable and accurate real-time control of medically-induced coma in a rodent model suggesting this strategy could be applied in patient care.

Vaccination with recombinant modified vaccinia virus Ankara prevents the onset of intestinal allergy in mice.

PubMed

Bohnen, C; Wangorsch, A; Schülke, S; Nakajima-Adachi, H; Hachimura, S; Burggraf, M; Süzer, Y; Schwantes, A; Sutter, G; Waibler, Z; Reese, G; Toda, M; Scheurer, S; Vieths, S

2013-08-01

Modified vaccinia virus Ankara (MVA)-encoding antigens are considered as safe vaccine candidates for various infectious diseases in humans. Here, we investigated the immune-modulating properties of MVA-encoding ovalbumin (MVA-OVA) on the allergen-specific immune response. The immune-modulating properties of MVA-OVA were investigated using GM-CSF-differentiated BMDCs from C57BL/6 mice. OVA expression upon MVA-OVA infection of BMDCs was monitored. Activation and maturation markers on viable MVA-OVA-infected mDCs were analyzed by flow cytometry. Secretion of INF-γ, IL-2, and IL-10 was determined in a co-culture of BMDCs infected with wtMVA or MVA-OVA and OVA-specific OT-I CD8(+) and OT-II CD4(+ ) T cells. BALB/c mice were vaccinated with wtMVA, MVA-OVA, or PBS, sensitized to OVA/alum and challenged with a diet containing chicken egg white. OVA-specific IgE, IgG1, and IgG2a and cytokine secretion from mesenteric lymph node (MLN) cells were analyzed. Body weight, body temperature, food uptake, intestinal inflammation, and health condition of mice were monitored. Infection with wtMVA and MVA-OVA induced comparable activation of mDCs. MVA-OVA-infected BMDCs expressed OVA and induced enhanced IFN-γ and IL-2 secretion from OVA-specific CD8(+ ) T cells in comparison with OVA, wtMVA, or OVA plus wtMVA. Prophylactic vaccination with MVA-OVA significantly repressed OVA-specific IgE, whereas OVA-specific IgG2a was induced. MVA-OVA vaccination suppressed TH 2 cytokine production in MLN cells and prevented the onset of allergic symptoms and inflammation in a mouse model of OVA-induced intestinal allergy. Modified vaccinia virus Ankara-ovalbumin (MVA-OVA) vaccination induces a strong OVA-specific TH 1- immune response, likely mediated by the induction of IFN-γ and IgG2a. Finally, MVA-based vaccines need to be evaluated for their therapeutic potential in established allergy models. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Microseismic monitoring: a tool for reservoir characterization.

NASA Astrophysics Data System (ADS)

Shapiro, S. A.

2011-12-01

Characterization of fluid-transport properties of rocks is one of the most important, yet one of most challenging goals of reservoir geophysics. There are some fundamental difficulties related to using active seismic methods for estimating fluid mobility. However, it would be very attractive to have a possibility of exploring hydraulic properties of rocks using seismic methods because of their large penetration range and their high resolution. Microseismic monitoring of borehole fluid injections is exactly the tool to provide us with such a possibility. Stimulation of rocks by fluid injections belong to a standard development practice of hydrocarbon and geothermal reservoirs. Production of shale gas and of heavy oil, CO2 sequestrations, enhanced recovery of oil and of geothermal energy are branches that require broad applications of this technology. The fact that fluid injection causes seismicity has been well-established for several decades. Observations and data analyzes show that seismicity is triggered by different processes ranging from linear pore pressure diffusion to non-linear fluid impact onto rocks leading to their hydraulic fracturing and strong changes of their structure and permeability. Understanding and monitoring of fluid-induced seismicity is necessary for hydraulic characterization of reservoirs, for assessments of reservoir stimulation and for controlling related seismic hazard. This presentation provides an overview of several theoretical, numerical, laboratory and field studies of fluid-induced microseismicity, and it gives an introduction into the principles of seismicity-based reservoir characterization.

A case of epilepsy induced by eating or by visual stimuli of food made of minced meat.

PubMed

Mimura, Naoya; Inoue, Takeshi; Shimotake, Akihiro; Matsumoto, Riki; Ikeda, Akio; Takahashi, Ryosuke

2017-08-31

We report a 34-year-old woman with eating epilepsy induced not only by eating but also seeing foods made of minced meat. In her early 20s of age, she started having simple partial seizures (SPS) as flashback and epigastric discomfort induced by particular foods. When she was 33 years old, she developed SPS, followed by secondarily generalized tonic-clonic seizure (sGTCS) provoked by eating a hot dog, and 6 months later, only seeing the video of dumpling. We performed video electroencephalogram (EEG) monitoring while she was seeing the video of soup dumpling, which most likely caused sGTCS. Ictal EEG showed rhythmic theta activity in the left frontal to mid-temporal area, followed by generalized seizure pattern. In this patient, seizures were provoked not only by eating particular foods but also by seeing these. This suggests a form of epilepsy involving visual stimuli.

STS-2 Induced Environment Contamination Monitor (IECM): Quick-Look Report

NASA Technical Reports Server (NTRS)

Miller, E. R. (Editor)

1982-01-01

The STS-2/induced environment contamination monitor (IECM) mission is described. The IECM system performance is discussed, and IECM mission time events are briefly described. Quick look analyses are presented for each of the 10 instruments comprising the IECM on the flight of STS-2. A short summary is presented.

Evaluating [11C]PBR28 PET for Monitoring Gut and Brain Inflammation in a Rat Model of Chemically Induced Colitis.

PubMed

Kurtys, E; Doorduin, J; Eisel, U L M; Dierckx, R A J O; de Vries, E F J

2017-02-01

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that affects an increasing number of patients. High comorbidity is observed between UC and other diseases in which inflammation may be involved, including brain diseases such as cognitive impairment, mental disorders, anxiety, and depression. To investigate the increased occurrence of these brain diseases in patients with UC, non-invasive methods for monitoring peripheral and central inflammation could be applied. Therefore, the goal of this study is to assess the feasibility of monitoring gut and brain inflammation in a rat model of chemically induced colitis by positron emission tomography (PET) with [ 11 C]PBR28, a tracer targeting the translocator protein (TSPO), which is upregulated when microglia and macrophages are activated. Colitis was induced in rats by intra-rectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Rats with colitis and healthy control animals were subjected to [ 11 C]PBR28 PET of the abdomen followed by ex vivo biodistribution in order to assess whether inflammation in the gut could be detected. Another group of rats with colitis underwent repetitive [ 11 C]PBR28 PET imaging of the brain to investigate the development of neuroinflammation. Eleven days after TNBS injection, ex vivo biodistribution studies demonstrated increased [ 11 C]PBR28 uptake in the inflamed cecum and colon of rats with colitis as compared to healthy controls, whereas PET imaging did not show any difference between groups at any time. Similarly, repetitive PET imaging of the brain did not reveal any neuroinflammation induced by the TNBS administration in the colon. In contrast, significantly increased [ 11 C]PBR28 uptake in cerebellum could be detected in ex vivo biodistribution studies on day 11. Inflammation in both the gut and the brain of rats with chemically induced colitis was observed by ex vivo biodistribution. However, these effects could not be detected by [ 11 C]PBR28 PET imaging in our colitis model, which is likely due to spill-over effects and insufficient resolution of the PET camera.

Reappraising the voices of wrath

PubMed Central

Frühholz, Sascha; Grandjean, Didier

2015-01-01

Cognitive reappraisal recruits prefrontal and parietal cortical areas. Because of the near exclusive usage in past research of visual stimuli to elicit emotions, it is unknown whether the same neural substrates underlie the reappraisal of emotions induced through other sensory modalities. Here, participants reappraised their emotions in order to increase or decrease their emotional response to angry prosody, or maintained their attention to it in a control condition. Neural activity was monitored with fMRI, and connectivity was investigated by using psychophysiological interaction analyses. A right-sided network encompassing the superior temporal gyrus, the superior temporal sulcus and the inferior frontal gyrus was found to underlie the processing of angry prosody. During reappraisal to increase emotional response, the left superior frontal gyrus showed increased activity and became functionally coupled to right auditory cortices. During reappraisal to decrease emotional response, a network that included the medial frontal gyrus and posterior parietal areas showed increased activation and greater functional connectivity with bilateral auditory regions. Activations pertaining to this network were more extended on the right side of the brain. Although directionality cannot be inferred from PPI analyses, the findings suggest a similar frontoparietal network for the reappraisal of visually and auditorily induced negative emotions. PMID:25964502

A conserved carboxylic acid group mediates light-dependent proton uptake and signaling by rhodopsin.

PubMed

Arnis, S; Fahmy, K; Hofmann, K P; Sakmar, T P

1994-09-30

A carboxylic acid residue is conserved at the cytoplasmic border of the third transmembrane segment among nearly all G protein-coupled receptors. In the visual receptor rhodopsin, replacement of the conserved Glu134 by a neutral glutamine results in enhanced transducin activation. Here we show that a key event in forming the active state of rhodopsin is proton uptake by Glu134 in the metarhodopsin II (MII) photoproduct. Site-directed mutants E134D and E134Q were studied by flash photolysis, where formation rates of their photoproducts and rates of pH change could be monitored simultaneously. Both mutants showed normal MII formation rates. However, E134D displayed a slowed rate of proton uptake and E134Q displayed a loss of light-induced uptake of two protons from the aqueous phase. Thus, Glu134 mediates light-dependent proton uptake by MII. We propose that receptor activation requires a light-induced conformational change that allows protonation of Glu134 and subsequent protonation of a second group. The strong conservation of Glu134 in G protein-coupled receptors implies a general requirement for a proton acceptor group at this position to allow light- or ligand-dependent receptor activation.

Changing body temperature affects the T2* signal in the rat brain and reveals hypothalamic activity.

PubMed

Vanhoutte, G; Verhoye, M; Van der Linden, A

2006-05-01

This study was designed to determine brain activity in the hypothalamus-in particular the thermoregulatory function of the hypothalamic preoptic area (PO). We experimentally changed the body temperature in rats within the physiological range (37-39 degrees C) and monitored changes in blood oxygenation level-dependent (BOLD) MR signal. To explore PO activity we had to deal with general signal changes caused by temperature-dependent alterations in the affinity of oxygen for hemoglobin, which contributes to BOLD contrast because it is partly sensitive to the amount of paramagnetic deoxyhemoglobin in the voxel. To reduce these overall temperature-induced effects, we corrected the BOLD data using brain-specific correction algorithms. The results showed activity of the PO during body warming from 38 degrees C to 39 degrees C, supported by an increased BOLD signal after correction. This is the first fMRI study on the autonomous nervous system in which hypothalamic activity elicited by changes in the internal environment (body temperature) was monitored. In this study we also demonstrate 1) that any fMRI study of anesthetized small animals should guard against background BOLD signal drift, since animals are vulnerable to body temperature fluctuations; and 2) the existence of a link between PO activity and the sympathetically-mediated opening of the arteriovenous anastomoses in a parallel study on the rat tail, a peripheral thermoregulatory organ.

A new impedance based approach to test the activity of recombinant protein--Semaphorins as a test case.

PubMed

Birger, Anastasya; Besser, Elazar; Reubinoff, Benjamin; Behar, Oded

2015-10-01

The biological activity of a recombinant protein is routinely measured using a bioassay such as an enzyme assay. However, many proteins have no enzymatic activity and in many cases it is difficult to devise a simple and reliable approach to test their activity. Semaphorins, Ephrins, Slits, Netrins or amylin-assisted proteins have numerous activities affecting many systems and cell types in the human body. Most of them are also able to induce rapid cytoskeleton changes at least in some cell types. We assumed therefore, that such proteins might be tested based on their ability to modulate the cytoskeleton. Here we tested a number of semaphorins in an impedance based label-free platform that allows for dynamic monitoring of subtle morphological and adhesive changes. This system has proved to be a very fast, sensitive and effective way to monitor and determine the activity of such proteins. Furthermore we showed that it is possible to customize a cell-protein system by transfecting the cells with specific receptors and test the cell response following the addition of the recombinant ligand protein. Since other protein families such as Ephrins and Netrins can also influence the cytoskeleton of some cells, this approach may be applicable to a large number of proteins. Copyright © 2015 Elsevier GmbH. All rights reserved.

Using laser-induced breakdown spectroscopy on vacuum alloys-production process for elements concentration analysis

NASA Astrophysics Data System (ADS)

Zhao, Tianzhuo; Fan, Zhongwei; Lian, Fuqiang; Liu, Yang; Lin, Weiran; Mo, Zeqiang; Nie, Shuzhen; Wang, Pu; Xiao, Hong; Li, Xin; Zhong, Qixiu; Zhang, Hongbo

2017-11-01

Laser-induced breakdown spectroscopy (LIBS) utilizing an echelle spectrograph-ICCD system is employed for on-line analysis of elements concentration in a vacuum induction melting workshop. Active temperature stabilization of echelle spectrometer is implemented specially for industrial environment applications. The measurement precision is further improved by monitoring laser parameters, such as pulse energy, spatial and temporal profiles, in real time, and post-selecting laser pulses with specific pulse energies. Experimental results show that major components of nickel-based alloys are stable, and can be well detected. By using internal standard method, calibration curves for chromium and aluminum are obtained for quantitative determination, with determination coefficient (relative standard deviation) to be 0.9559 (< 2.2%) and 0.9723 (< 2.8%), respectively.

Does the Loss of Stromal Caveolin-1 Remodel the Tumor Microenvironment by Activating Src-Mediated PEAK1 and PI3K Pathways

DTIC Science & Technology

2017-11-01

and PI3K Pathways? PRINCIPAL INVESTIGATOR: MARIANA REIS SOBREIRO PhD CONTRACTING ORGANIZATION: Cedars-Sinai Medical Center Los Angeles, CA 90048...BEVERLY BLVD LOS ANGELES CA 90048-1804 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical...oncosomes ( LO ). LO internalization induces reprogramming of human normal prostate fibroblasts, as reflected by high levels of α-SMA, IL6, and MMP9. In

Src-JNK Potentiation of Estrogen Receptor AF-1; Mechanism, and Role in Estrogen Action in Breast Cancer

DTIC Science & Technology

2002-08-01

an increase in estrogen receptor activity. A second objective is to understand the potential role of Src in estrogen induced mammary ductal development ...bPcis i on to The Ser-ilS-dependent link wt GR- t KaroBio AB, a Swedish pharmaceutical development company with CBP is in addition to the Ser-1l8...the ECL detection kit (Amersham Pharmacia Biotech ). phoresis, stained with Coomassic Blue to monitor expression, and sub- Fluorescence Microscopy

Measuring ground movement in geothermal areas of Imperial Valley, California

NASA Technical Reports Server (NTRS)

Lofgren, B. E.

1974-01-01

Significant ground movement may accompany the extraction of large quantities of fluids from the subsurface. In Imperial Valley, California, one of the potential hazards of geothermal development is the threat of both subsidence and horizontal movement of the land surface. Regional and local survey nets are being monitored to detect and measure possible ground movement caused by future geothermal developments. Precise measurement of surface and subsurface changes will be required to differentiate man-induced changes from natural processes in this tectonically active region.

Geothermal hazards - Mercury emission

NASA Technical Reports Server (NTRS)

Siegel, S. M.; Siegel, B. Z.

1975-01-01

Enthusiasm for intensified geothermal exploration may induce many participants to overlook a long-term potential toxicity hazard possibly associated with the tapping of magmatic steam. The association of high atmospheric Hg levels with geothermal activity has been established both in Hawaii and Iceland, and it has been shown that mercury can be introduced into the atmosphere from fumaroles, hot springs, and magmatic sources. These arguments, extended to thallium, selenium, and other hazardous elements, underscore the need for environmental monitoring in conjunction with the delivery of magmatic steam to the surface.

Reliability assessment of multiple quantum well avalanche photodiodes

NASA Technical Reports Server (NTRS)

Yun, Ilgu; Menkara, Hicham M.; Wang, Yang; Oguzman, Isamil H.; Kolnik, Jan; Brennan, Kevin F.; May, Gray S.; Wagner, Brent K.; Summers, Christopher J.

1995-01-01

The reliability of doped-barrier AlGaAs/GsAs multi-quantum well avalanche photodiodes fabricated by molecular beam epitaxy is investigated via accelerated life tests. Dark current and breakdown voltage were the parameters monitored. The activation energy of the degradation mechanism and median device lifetime were determined. Device failure probability as a function of time was computed using the lognormal model. Analysis using the electron beam induced current method revealed the degradation to be caused by ionic impurities or contamination in the passivation layer.

Monitoring-induced disruption in skilled typewriting.

PubMed

Snyder, Kristy M; Logan, Gordon D

2013-10-01

It is often disruptive to attend to the details of one's expert performance. The current work presents four experiments that utilized a monitor to report protocol to evaluate the sufficiency of three accounts of monitoring-induced disruption. The inhibition hypothesis states that disruption results from costs associated with preparing to withhold inappropriate responses. The dual-task hypothesis states that disruption results from maintaining monitored information in working memory. The implicit-explicit hypothesis states that disruption results from explicitly monitoring details of performance that are normally implicit. The findings suggest that all three hypotheses are sufficient to produce disruption, but inhibition and dual-task costs are not necessary. Experiment 1 showed that monitoring to report was disruptive even when there was no requirement to inhibit. Experiment 2 showed that maintaining information in working memory caused some disruption but much less than monitoring to report. Experiment 4 showed that monitoring to inhibit was more disruptive than monitoring to report, suggesting that monitoring is more disruptive when it is combined with other task requirements, such as inhibition. PsycINFO Database Record (c) 2013 APA, all rights reserved.

7 CFR 800.216 - Activities that shall be monitored.

Code of Federal Regulations, 2014 CFR

2014-01-01

... REGULATIONS Supervision, Monitoring, and Equipment Testing § 800.216 Activities that shall be monitored. (a...) Grain merchandising activities. Grain merchandising activities subject to monitoring for compliance with.... Grain handling activities subject to monitoring for compliance with the Act include but are not limited...

7 CFR 800.216 - Activities that shall be monitored.

Code of Federal Regulations, 2013 CFR

2013-01-01

... REGULATIONS Supervision, Monitoring, and Equipment Testing § 800.216 Activities that shall be monitored. (a...) Grain merchandising activities. Grain merchandising activities subject to monitoring for compliance with.... Grain handling activities subject to monitoring for compliance with the Act include but are not limited...

7 CFR 800.216 - Activities that shall be monitored.

Code of Federal Regulations, 2011 CFR

2011-01-01

... REGULATIONS Supervision, Monitoring, and Equipment Testing § 800.216 Activities that shall be monitored. (a...) Grain merchandising activities. Grain merchandising activities subject to monitoring for compliance with.... Grain handling activities subject to monitoring for compliance with the Act include but are not limited...

7 CFR 800.216 - Activities that shall be monitored.

Code of Federal Regulations, 2010 CFR

2010-01-01

... REGULATIONS Supervision, Monitoring, and Equipment Testing § 800.216 Activities that shall be monitored. (a...) Grain merchandising activities. Grain merchandising activities subject to monitoring for compliance with.... Grain handling activities subject to monitoring for compliance with the Act include but are not limited...

Inhibition of immobilization stress-induced anorexia, behavioral deficits, and plasma corticosterone secretion by injected leptin in rats.

PubMed

Haque, Zeba; Akbar, Nazia; Yasmin, Farzana; Haleem, Muhammad A; Haleem, Darakhshan J

2013-05-01

Leptin, originally identified as an anti-obesity hormone, also has an important role in the regulation of mood and emotion. The present study was designed to monitor effects of injected leptin on immobilization stress-induced anorexia, behavioral deficits, and plasma corticosterone secretion in rats. Exposure to 2 h immobilization stress decreased food intake and body weight in saline-injected animals. Animals exposed to open field, elevated plus maze, and light-dark transition tests the day following immobilization exhibited anxiety-like behavior. Leptin injected at doses of 0.1 and 0.5 mg/kg also decreased food intake and body weight in unstressed animals and elicited anxiolytic effects at dose of 0.5 mg/kg, monitored on the following day. Immobilization-induced decreases in food intake, body weight, as well as stress-induced behavioral deficits in the open field, elevated plus maze, and light-dark transition test were reversed by exogenous leptin in a dose-dependent (0.1-0.5 mg/kg) manner. Acute exposure to 2 h immobilization produced a fourfold rise in plasma levels of corticosterone. Animals injected with leptin at a dose of 0.1 mg/kg, but not at dose of 0.5 mg/kg, exhibited a marginal increase in plasma corticosterone. Immobilization-induced increases of plasma corticosterone were reversed by leptin injected at doses of 0.1 or 0.5 mg/kg. The data suggest that exogenous leptin can reduce stress perception, resulting in an inhibition of stress effects on the activity of hypothalamic-pituitary-adrenal axis and behavior. The reported pharmacological effects of leptin represent an innovative approach for the treatment of stress-related disorders.

Developmental and hormone-induced changes of mitochondrial electron transport chain enzyme activities during the last instar larval development of maize stem borer, Chilo partellus (Lepidoptera: Crambidae).

PubMed

VenkatRao, V; Chaitanya, R K; Naresh Kumar, D; Bramhaiah, M; Dutta-Gupta, A

2016-12-01

The energy demand for structural remodelling in holometabolous insects is met by cellular mitochondria. Developmental and hormone-induced changes in the mitochondrial respiratory activity during insect metamorphosis are not well documented. The present study investigates activities of enzymes of mitochondrial electron transport chain (ETC) namely, NADH:ubiquinone oxidoreductase or complex I, Succinate: ubiquinone oxidoreductase or complex II, Ubiquinol:ferricytochrome c oxidoreductase or complex III, cytochrome c oxidase or complex IV and F 1 F 0 ATPase (ATPase), during Chilo partellus development. Further, the effect of juvenile hormone (JH) analog, methoprene, and brain and corpora-allata-corpora-cardiaca (CC-CA) homogenates that represent neurohormones, on the ETC enzyme activities was monitored. The enzymatic activities increased from penultimate to last larval stage and thereafter declined during pupal development with an exception of ATPase which showed high enzyme activity during last larval and pupal stages compared to the penultimate stage. JH analog, methoprene differentially modulated ETC enzyme activities. It stimulated complex I and IV enzyme activities, but did not alter the activities of complex II, III and ATPase. On the other hand, brain homogenate declined the ATPase activity while the injected CC-CA homogenate stimulated complex I and IV enzyme activities. Cumulatively, the present study is the first to show that mitochondrial ETC enzyme system is under hormone control, particularly of JH and neurohormones during insect development. Copyright © 2015 Elsevier Inc. All rights reserved.

The USGS geomagnetism program and its role in space weather monitoring

USGS Publications Warehouse

Love, Jeffrey J.; Finn, Carol A.

2011-01-01

Magnetic storms result from the dynamic interaction of the solar wind with the coupled magnetospheric-ionospheric system. Large storms represent a potential hazard for the activities and infrastructure of a modern, technologically based society [Baker et al., 2008]; they can cause the loss of radio communications, reduce the accuracy of global positioning systems, damage satellite electronics and affect satellite operations, increase pipeline corrosion, and induce voltage surges in electric power grids, causing blackouts. So while space weather starts with the Sun and is driven by the solar wind, it is on, or just above, the surface of the Earth that the practical effects of space weather are realized. Therefore, ground-based sensor networks, including magnetic observatories [Love, 2008], play an important role in space weather monitoring.

The USGS Geomagnetism Program and its role in Space-Weather Monitoring

USGS Publications Warehouse

Love, Jeffrey J.; Finn, Carol A.

2011-01-01

Magnetic storms result from the dynamic interaction of the solar wind with the coupled magnetospheric-ionospheric system. Large storms represent a potential hazard for the activities and infrastructure of a modern, technologically based society [Baker et al., 2008]; they can cause the loss of radio communications, reduce the accuracy of global positioning systems, damage satellite electronics and affect satellite operations, increase pipeline corrosion, and induce voltage surges in electric power grids, causing blackouts. So while space weather starts with the Sun and is driven by the solar wind, it is on, or just above, the surface of the Earth that the practical effects of space weather are realized. Therefore, ground-based sensor networks, including magnetic observatories [Love, 2008], play an important role in space weather monitoring.

Effects of euthanasia on brain physiological activities monitored in real-time.

PubMed

Mayevsky, Avraham; Barbiro-Michaely, Efrat; Ligeti, Laszlo; MacLaughlin, Alan C

2002-10-01

Animal experimentation is terminated by the euthanasia procedure in order to avoid pain and minimize suffering. Very little is known about the real time physiological changes taking place in the brain of animals during the euthanasia. Since there is no way to evaluate the suffering of animals under euthanasia, it is assumed that objective physiological changes taking place could serve as a good way to compare various types of euthanasia procedures. In the present study we compared the effect of euthanasia induced by i. v. injection of concentrated KCL to that of Taxan T-61 (a standard mixture used by veterinarians). The responses of the cat brain were evaluated by monitoring the hemodynamic (CBF), metabolic (NADH redox state), electrical (EcoG) and extracellular ion levels, as an indicator to the ionic homeostasis.

Monitoring Ligand-Activated Protein-Protein Interactions Using Bioluminescent Resonance Energy Transfer (BRET) Assay.

PubMed

Coriano, Carlos; Powell, Emily; Xu, Wei

2016-01-01

The bioluminescent resonance energy transfer (BRET) assay has been extensively used in cell-based and in vivo imaging systems for detecting protein-protein interactions in the native environment of living cells. These protein-protein interactions are essential for the functional response of many signaling pathways to environmental chemicals. BRET has been used as a toxicological tool for identifying chemicals that either induce or inhibit these protein-protein interactions. This chapter focuses on describing the toxicological applications of BRET and its optimization as a high-throughput detection system in live cells. Here we review the construction of BRET fusion proteins, describe the BRET methodology, and outline strategies to overcome obstacles that may arise. Furthermore, we describe the advantage of BRET over other resonance energy transfer methods for monitoring protein-protein interactions.

Wireless remote monitoring of myocardial ischemia using reconstructed 12-lead ECGs.

PubMed

Vukcevic, Vladan; Panescu, Dorin; Bojovic, Bosko; George, Samuel; Gussak, Ihor; Giga, Vojislav; Stankovic, Ivana

2010-01-01

CardioBip (CB) is a hand-held patient-activated device for recording and wireless transmission of reconstructed 12-lead ECG (12CB) based on patient specific matrices. It has 5 contact points: 3 precordial and 2 on the device top serving as limb leads when touched by index fingers. To determine whether CB could be used to monitor coronary disease (CAD) patients, we compared 12CB to simultaneous 12-lead ECGs (12L) in patients with CAD, pre-and post-exercise treadmill testing (ETT). The study goals were to assess: (1) whether 12CB can accurately reconstruct and wirelessly transmit 12-lead ECGs in CAD patients during ETT recovery; (2) whether 12CB can be used to evaluate ST segment changes in patients with exercise-induced ischemia.

InSAR MSBAS Time-Series Analysis of Induced Seismicity in Colorado and Oklahoma

NASA Astrophysics Data System (ADS)

Barba, M.; Tiampo, K. F.; Samsonov, S. V.

2016-12-01

Since 2009, the number of earthquakes in the central and eastern United States has dramatically increased from an average of 24 M ≥ 3 earthquakes a year (1973-2008) to an average of 193 M ≥ 3 earthquakes a year (2009-2014) (Ellsworth, 2013). Wastewater injection, the deep disposal of fluids, is considered to be the primary reason for this increase in seismicity rate (Weingarten et al., 2015). We use Interferometric Synthetic Aperture Radar (InSAR) to study four potential regions with injection induced seismicity: Greely, CO, Platteville, CO, Edmond, OK, and Jones, OK. Currently, Platteville is not seismically active; however, it serves as a baseline since its high-volume injection wells have the potential to induce future earthquakes. InSAR data complements seismic data by providing insight into the surface deformation potentially correlated with earthquake activity. To study the ground deformation associated with the induced seismicity and injection well activity, we develop full-resolution interferograms using raw radar data from Radarsat-1/2, ERS-1/2, Envisat, ALOS, and Sentinel-1. We pair the SAR images using the small perpendicular baseline approach (Berardino et al., 2002) to minimize spatial decorrelation. The paired SAR images are processed into interferograms using the JPL ISCE software (Gurrola et al., 2010). Using the MSBAS algorithm (Samsonov et al., 2013, Samsonov and d'Oreye, 2012) and the JPL GIAnT software (Agram et al., 2013), we construct a time-series of the cumulative surface displacement, integrating all interferograms for the region. To correlate the relationship between surface deformation and wastewater injection, we compare the well locations, depths, and injection rates with the spatial and temporal signature of the surface deformation before and after induced earthquakes, filling in the spatiotemporal gap lacking from seismicity. By monitoring the surface deformation for wells associated with past and current induced seismicity, we can implement measures to mitigate induced seismicity and its social and economic impact.

Pilot performance in zero-visibility precision approach. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Ephrath, A. R.

1975-01-01

The pilot's short-term decisions regarding performance assessment and failure monitoring is examined. The performance of airline pilots who flew simulated zero-visibility landing approaches is reported. Results indicate that the pilot's mode of participation in the control task has a strong effect on his workload, the induced workload being lowest when the pilot acts as a monitor during a coupled approach and highest when the pilot is an active element in the control loop. A marked increase in workload at altitudes below 500 ft. is documented at all participation modes; this increase is inversely related to distance-to-go. The participation mode is shown to have a dominant effect on failure-detection performance, with a failure in a monitored (coupled) axis being detected faster than a comparable failure in a manually-controlled axis. Touchdown performance is also documented. It is concluded that the conventional instrument panel and its associated displays are inadequate for zero-visibility operations in the final phases of the landing approach.

An iridium oxide microelectrode for monitoring acute local pH changes of endothelial cells.

PubMed

Ng, Shu Rui; O'Hare, Danny

2015-06-21

pH sensors were fabricated by anodically electrodepositing iridium oxide films (AEIROFs) onto microelectrodes on chips and coated with poly(ethyleneimine) (PEI) for mechanical stability. These demonstrate super-Nernstian response to pH from pH 4.0 to 7.7 in chloride-free phosphate buffer. The surface of the chip was coated with fibronectin for the attachment of porcine aortic endothelial cells (PAECs). The working capability of the pH sensor for monitoring acute local pH changes was investigated by stimulating the PAECs with thrombin. Our results show that thrombin induced acute extracellular acidification of PAECs and dissolution of fibronectin, causing the local pH to decrease. The use of PD98059, a mitogen-activated protein kinase (MAPK) inhibitor, reduced extracellular acidification and an increase in local pH was observed. This study shows that our pH sensors can facilitate the investigation of acute cellular responses to stimulation by monitoring the real-time, local pH changes of cells attached to the sensors.

Protease-activated receptor-2 stimulates intestinal epithelial chloride transport through activation of PLC and selective PKC isoforms.

PubMed

van der Merwe, Jacques Q; Moreau, France; MacNaughton, Wallace K

2009-06-01

Serine proteases play important physiological roles through their activity at G protein-coupled protease-activated receptors (PARs). We examined the roles that specific phospholipase (PL) C and protein kinase (PK) C (PKC) isoforms play in the regulation of PAR(2)-stimulated chloride secretion in intestinal epithelial cells. Confluent SCBN epithelial monolayers were grown on Snapwell supports and mounted in modified Ussing chambers. Short-circuit current (I(sc)) responses to basolateral application of the selective PAR(2) activating peptide, SLIGRL-NH(2), were monitored as a measure of net electrogenic ion transport caused by PAR(2) activation. SLIGRL-NH(2) induced a transient I(sc) response that was significantly reduced by inhibitors of PLC (U73122), phosphoinositol-PLC (ET-18), phosphatidylcholine-PLC (D609), and phosphatidylinositol 3-kinase (PI3K; LY294002). Immunoblot analysis revealed the phosphorylation of both PLCbeta and PLCgamma following PAR(2) activation. Pretreatment of the cells with inhibitors of PKC (GF 109203X), PKCalpha/betaI (Gö6976), and PKCdelta (rottlerin), but not PKCzeta (selective pseudosubstrate inhibitor), also attenuated this response. Cellular fractionation and immunoblot analysis, as well as confocal immunocytochemistry, revealed increases of PKCbetaI, PKCdelta, and PKCepsilon, but not PKCalpha or PKCzeta, in membrane fractions following PAR(2) activation. Pretreatment of the cells with U73122, ET-18, or D609 inhibited PKC activation. Inhibition of PI3K activity only prevented PKCdelta translocation. Immunoblots revealed that PAR(2) activation induced phosphorylation of both cRaf and ERK1/2 via PKCdelta. Inhibition of PKCbetaI and PI3K had only a partial effect on this response. We conclude that basolateral PAR(2)-induced chloride secretion involves activation of PKCbetaI and PKCdelta via a PLC-dependent mechanism resulting in the stimulation of cRaf and ERK1/2 signaling.

Multidisciplinary Approach to Identify and Mitigate the Hazard from Induced Seismicity in Oklahoma

NASA Astrophysics Data System (ADS)

Holland, A. A.; Keller, G. R., Jr.; Darold, A. P.; Murray, K. E.; Holloway, S. D.

2014-12-01

Oklahoma has experienced a very significant increase in seismicity rates over the last 5 years with the greatest increase occurring in 2014. The observed rate increase indicates that the seismic hazard for at least some parts of Oklahoma has increased significantly. Many seismologists consider the large number of salt-water disposal wells operating in Oklahoma as the largest contributing factor to this increase. However, unlike many cases of seismicity induced by injection, the greatest increase is occurring over a very large area, about 15% of the state. There are more than 3,000 disposal wells currently operating within Oklahoma along with injection volumes greater than 2010 rates. These factors add many significant challenges to identifying potential cases of induced seismicity and understanding the contributing factors well enough to mitigate such occurrences. In response to a clear need for a better geotechnical understanding of what is occurring in Oklahoma, a multi-year multidisciplinary study some of the most active areas has begun at the University of Oklahoma. This study includes additional seismic monitoring, better geological and geophysical characterization of the subsurface, hydrological and reservoir modeling, and geomechanical studies to better understand the rise in seismicity rates. The Oklahoma Corporation Commission has added new rules regarding reporting and monitoring of salt-water disposal wells, and continue to work with the Oklahoma Geological Survey and other researchers.

A new infusion pathway monitoring system utilizing electrostatic induced potential.

PubMed

Maki, Hiromichi; Yonezawa, Yoshiharu; Ogawa, Hidekuni; Ninomiya, Ishio; Sada, Kouji; Hamada, Shingo; Hahn, Alien W; Caldwell, W Morton

2006-01-01

We have developed a new infusion pathway monitoring system employing linear integrated circuits and a low-power 8-bit single chip microcomputer. The system is available for hospital and home use and it constantly monitors the intactness of the pathway. The sensor is an electro-conductive polymer electrode wrapped around the infusion polyvinyl chloride infusion tube. This records an AC (alternating current) voltage induced on the patient's body by electrostatic coupling from the normal 100 volt, 60 Hz AC power line wiring field in the patient's room. If the injection needle or infusion tube becomes detached, then the system detects changes in the induced AC voltage and alerts the nursing station, via the nurse call system or PHS (personal handy phone System).

Asiatic acid attenuates methamphetamine-induced neuroinflammation and neurotoxicity through blocking of NF-kB/STAT3/ERK and mitochondria-mediated apoptosis pathway.

PubMed

Park, Ji-Hyun; Seo, Young Ho; Jang, Jung-Hee; Jeong, Chul-Ho; Lee, Sooyeun; Park, Byoungduck

2017-12-11

Methamphetamine (METH) is a commonly abused drug that may result in neurotoxic effects. Recent studies have suggested that involvement of neuroinflammatory processes in brain dysfunction is induced by misuse of this drug. However, the mechanism underlying METH-induced inflammation and neurotoxicity in neurons is still unclear. In this study, we investigated whether asiatic acid (AA) effected METH-mediated neuroinflammation and neurotoxicity in dopaminergic neuronal cells. And we further determined whether the effect involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT)3 and extracellular signal-regulated kinase (ERK) pathway. We used the human dopaminergic neuroblastoma SH-SY5Y cell line, murine microglial BV2 cell line, and primary culture of rat embryo mesencephalic neurons. Pro-inflammatory cytokine production was monitored by ELISA and RT/real-time PCR. The cell cycle distribution and mitochondrial membrane integrity was analyzed by flow cytometry. We used immunoblotting, DNA-binding activity, and immunofluorescence staining to analyze the effect of AA on activation of the NF-κB, STAT3, MAPK-ERK, and apoptosis signaling pathways. METH induced TNF receptor (TNFR) expression and led to morphological changes of cells. Additionally, this drug increased pro-inflammatory cytokine (TNFα and IL-6) expression. AA significantly suppressed METH-induced TNFR expression in concentration dependent. Increased secretion of TNFα and IL-6 was inhibited in METH-stimulated neuronal cells by AA administration. AA showed significant protection against METH-induced translocation of NF-κB/STAT3 and ERK phosphorylation. AA inhibited METH-induced proteolytic fragmentation of caspase-3 and PARP. The pro-apoptotic protein Bax was significantly decreased, while the anti-apoptotic protein Bcl-xL was increased by AA treatment in METH-stimulated cells. A similar protective effect of AA on mitochondrial membrane integrity was also confirmed by flow cytometry and immunofluorescence staining. Based on the literatures and our findings, AA is a promising candidate for an anti-neurotoxic agent, and it can potentially be used for the prevention and treatment of various neurological disorders.

Evaluation of hair growth promoting activity of Phyllanthus niruri

PubMed Central

Patel, Satish; Sharma, Vikas; S. Chauhan, Nagendra; Thakur, Mayank; Dixit, Vinod Kumar

2015-01-01

Objective: This study was designed to investigate the potential Phyllanthus niruri (P. niruri ) extracts in promotion of hair growth. Materials and Methods: Here, we studied the hair growth promoting activity of petroleum ether extract of P. niruri following its topical administration. Alopecia was induced in albino rats by subcutaneous administration of testosterone for 21 days. Evaluation of hair loss inhibition was done by concurrent administration of extract and monitoring parameters like follicular density, anagen/telogen (A/T) ratio and histological observation of animal skin sections. Finasteride solution was applied topically as standard. In vitro experiments were also performed to study the effect of extract on the activity of 5α-reductase enzyme Results: Groups treated with petroleum ether extract of plant showed hair re-growth as reflected by follicular density, A/T ratio and skin sections. Histopathology and morphologic observations of hair re-growth at shaved sites showed active follicular proliferation. In vitro experiments results showed inhibitory activity of petroleum ether extract on type-2 5α-reductase enzyme and an increase in the amount of testosterone with increasing concentrations. Conclusion: It could be concluded that petroleum ether extracts of P. niruri might be useful in the treatment of testosterone-induced alopecia in the experimental animal by inhibiting 5α-reductase enzyme. PMID:26693408

Bone structure and quality preserved by active versus passive muscle exercise in 21 days tail-suspended rats

NASA Astrophysics Data System (ADS)

Luan, Huiqin; Sun, Lian-wen; Fan, Yu-bo

2012-07-01

Humans in Space suffer from microgravity-induced attenuated bone strength that needs to be addressed by on-orbit exercise countermeasures. However, exercise prescriptions so far did not adequately counteract the bone loss of astronauts in spaceflight because even active muscle contractions were converted to passive mode during voluntary bouts. We tested our hypothesis in unloaded rat hind limb following twenty-one days of tail-suspension (TS) combined with exercise using a hind limb stepper device designed by our group. Female Sprague Dawley rats (250g b.wt.) were divided into four groups (n=5, each): TS-only (hind limb unloading), TS plus passive mode exercise (TSP) induced by mechanically-forced passive hind limb lifting, TS plus active mode exercise (TSA) entrained by plantar electrostimulation, and control (CON) group. Standard measures of bone (e.g., mineral density, trabecular microstructure, biomechanics and ash weight) were monitored. Results provided that the attenuated properties of unloaded hind limb bone in TS-rats were more effectively supported by active mode than by passive mode motions. We here propose a modified exercise regimen combined with spontaneous muscle contractions thereby considering the biodynamic demands of both muscle and bone during resistive-load exercise in microgravity. Keywords: rat, BMD, DXA, passive exercise, active exercise, bone loss, tail suspension, spaceflight analogue, exercise countermeasure.

Voltage- and current-activated metal-insulator transition in VO2-based electrical switches: a lifetime operation analysis.

PubMed

Crunteanu, Aurelian; Givernaud, Julien; Leroy, Jonathan; Mardivirin, David; Champeaux, Corinne; Orlianges, Jean-Christophe; Catherinot, Alain; Blondy, Pierre

2010-12-01

Vanadium dioxide is an intensively studied material that undergoes a temperature-induced metal-insulator phase transition accompanied by a large change in electrical resistivity. Electrical switches based on this material show promising properties in terms of speed and broadband operation. The exploration of the failure behavior and reliability of such devices is very important in view of their integration in practical electronic circuits. We performed systematic lifetime investigations of two-terminal switches based on the electrical activation of the metal-insulator transition in VO 2 thin films. The devices were integrated in coplanar microwave waveguides (CPWs) in series configuration. We detected the evolution of a 10 GHz microwave signal transmitted through the CPW, modulated by the activation of the VO 2 switches in both voltage- and current-controlled modes. We demonstrated enhanced lifetime operation of current-controlled VO 2 -based switching (more than 260 million cycles without failure) compared with the voltage-activated mode (breakdown at around 16 million activation cycles). The evolution of the electrical self-oscillations of a VO 2 -based switch induced in the current-operated mode is a subtle indicator of the material properties modification and can be used to monitor its behavior under various external stresses in sensor applications.

Production of induced secondary metabolites by a co-culture of sponge-associated actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163.

PubMed

Dashti, Yousef; Grkovic, Tanja; Abdelmohsen, Usama Ramadan; Hentschel, Ute; Quinn, Ronald J

2014-05-22

Two sponge-derived actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163, were grown in co-culture and the presence of induced metabolites monitored by ¹H NMR. Ten known compounds, including angucycline, diketopiperazine and β-carboline derivatives 1-10, were isolated from the EtOAc extracts of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163. Co-cultivation of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163 induced the biosynthesis of three natural products that were not detected in the single culture of either microorganism, namely N-(2-hydroxyphenyl)-acetamide (11), 1,6-dihydroxyphenazine (12) and 5a,6,11a,12-tetrahydro-5a,11a-dimethyl[1,4]benzoxazino[3,2-b][1,4]benzoxazine (13a). When tested for biological activity against a range of bacteria and parasites, only the phenazine 12 was active against Bacillus sp. P25, Trypanosoma brucei and interestingly, against Actinokineospora sp. EG49. These findings highlight the co-cultivation approach as an effective strategy to access the bioactive secondary metabolites hidden in the genomes of marine actinomycetes.

Influence of thyroid status on hepatic alpha 1-adrenoreceptor responsiveness.

PubMed

Daza, F J; Parrilla, R; Martín-Requero, A

1997-12-01

The present work aimed to elucidate the influence of thyroid functional status on the alpha 1-adrenoreceptor-induced activation of hepatic metabolic functions. The experiments were performed in either a nonrecirculating liver perfusion system featuring continuous monitoring of portal pressure, PO2, pCa, and pH, or isolated hepatocytes from euthyroid, hyperthyroid, and hypothyroid rats. Hypothyroidism decreased the alpha 1-adrenergic stimulation of respiration, glycogen breakdown, and gluconeogenesis. These effects were accompanied by a decreased intracellular Ca2+ mobilization corroborating that those processes are regulated by the Ca(2+)-dependent branch of the alpha 1-adrenoreceptor signaling pathway. Moreover, in hyperthyroid rats the alpha 1-adrenergic-induced increase in cytosolic Ca2+ was enhanced, and glucose synthesis or mobilization was not altered. The thyroid status influenced neither the alpha 1-adrenergic stimulation of vascular smooth muscle contraction nor the alpha 1-agonist-induced intracellular alkalinization and protein kinase C (PKC) activation. Thus the distinct impairment of the Ca(2+)-dependent branch of the alpha 1-adrenoreceptor signaling pathway by thyroid status provides a useful tool to investigate the role played by each signaling pathway, Ca2+ or PKC, in controlling hepatic functions.

Differential cytotoxicity induced by the Titanium(IV)Salan complex Tc52 in G2-phase independent of DNA damage.

PubMed

Pesch, Theresa; Schuhwerk, Harald; Wyrsch, Philippe; Immel, Timo; Dirks, Wilhelm; Bürkle, Alexander; Huhn, Thomas; Beneke, Sascha

2016-07-13

Chemotherapy is one of the major treatment modalities for cancer. Metal-based compounds such as derivatives of cisplatin are in the front line of therapy against a subset of cancers, but their use is restricted by severe side-effects and the induction of resistance in treated tumors. Subsequent research focused on development of cytotoxic metal-complexes without cross-resistance to cisplatin and reduced side-effects. This led to the discovery of first-generation titanium(IV)salan complexes, which reached clinical trials but lacked efficacy. New-generation titanium (IV)salan-complexes show promising anti-tumor activity in mice, but their molecular mechanism of cytotoxicity is completely unknown. Four different human cell lines were analyzed in their responses to a toxic (Tc52) and a structurally highly related but non-toxic (Tc53) titanium(IV)salan complex. Viability assays were used to reveal a suitable treatment range, flow-cytometry analysis was performed to monitor the impact of dosage and treatment time on cell-cycle distribution and cell death. Potential DNA strand break induction and crosslinking was investigated by immunostaining of damage markers as well as automated fluorometric analysis of DNA unwinding. Changes in nuclear morphology were analyzed by DAPI staining. Acidic beta-galactosidase activity together with morphological changes was monitored to detect cellular senescence. Western blotting was used to analyze induction of pro-apoptotic markers such as activated caspase7 and cleavage of PARP1, and general stress kinase p38. Here we show that the titanium(IV)salan Tc52 is effective in inducing cell death in the lower micromolar range. Surprisingly, Tc52 does not target DNA contrary to expectations deduced from the reported activity of other titanium complexes. Instead, Tc52 application interferes with progression from G2-phase into mitosis and induces apoptotic cell death in tested tumor cells. Contrarily, human fibroblasts undergo senescence in a time and dose-dependent manner. As deduced from fluorescence studies, the potential cellular target seems to be the cytoskeleton. In summary, we could demonstrate in four different human cell lines that tumor cells were specifically killed without induction of major cytotoxicity in non-tumorigenic cells. Absence of DNA damaging activity and the cell-cycle block in G2 instead of mitosis makes Tc52 an attractive compound for further investigations in cancer treatment.

A pH-sensitive fluor, CypHer 5, used to monitor agonist-induced G protein-coupled receptor internalization in live cells.

PubMed

Adie, E J; Kalinka, S; Smith, L; Francis, M J; Marenghi, A; Cooper, M E; Briggs, M; Michael, N P; Milligan, G; Game, S

2002-11-01

G protein-coupled receptors (GPCRs) are the largest family of proteins involved in transmembrane signal transduction and are actively studied because of their suitability as therapeutic small-molecule drug targets. Agonist activation of GPCRs almost invariably results in the receptor being desensitized. One of the key events in receptor desensitization is the sequestration of the receptor from the cell surface into acidic intracellular endosomes. Therefore, a convenient, generic, and noninvasive monitor of this process is desirable. A novel, pH-sensitive, red-excited fluorescent dye, CypHer 5, was synthesized. This dye is non-fluorescent at neutral pH and is fluorescent at acidic pH. Anti-epitope antibodies labeled with this dye were internalized in an agonist concentration- and time-dependent manner, following binding on live cells to a range of GPCRs that had been modified to incorporate the epitope tags in their extracellular N-terminal domain. This resulted in a large signal increase over background. When protonated, the red fluorescence of CypHer 5 provides a generic reagent suitable for monitoring the internalization of GPCRs into acidic vesicles. This approach should be amenable to the study of many other classes of cell surface receptors that also internalize following stimulation.

Transparent Stretchable Self-Powered Patchable Sensor Platform with Ultrasensitive Recognition of Human Activities.

PubMed

Hwang, Byeong-Ung; Lee, Ju-Hyuck; Trung, Tran Quang; Roh, Eun; Kim, Do-Il; Kim, Sang-Woo; Lee, Nae-Eung

2015-09-22

Monitoring of human activities can provide clinically relevant information pertaining to disease diagnostics, preventive medicine, care for patients with chronic diseases, rehabilitation, and prosthetics. The recognition of strains on human skin, induced by subtle movements of muscles in the internal organs, such as the esophagus and trachea, and the motion of joints, was demonstrated using a self-powered patchable strain sensor platform, composed on multifunctional nanocomposites of low-density silver nanowires with a conductive elastomer of poly(3,4-ethylenedioxythiophene):polystyrenesulfonate/polyurethane, with high sensitivity, stretchability, and optical transparency. The ultra-low-power consumption of the sensor, integrated with both a supercapacitor and a triboelectric nanogenerator into a single transparent stretchable platform based on the same nanocomposites, results in a self-powered monitoring system for skin strain. The capability of the sensor to recognize a wide range of strain on skin has the potential for use in new areas of invisible stretchable electronics for human monitoring. A new type of transparent, stretchable, and ultrasensitive strain sensor based on a AgNW/PEDOT:PSS/PU nanocomposite was developed. The concept of a self-powered patchable sensor system integrated with a supercapacitor and a triboelectric nanogenerator that can be used universally as an autonomous invisible sensor system was used to detect the wide range of strain on human skin.

Circadian rhythm resynchronization improved isoflurane-induced cognitive dysfunction in aged mice.

PubMed

Song, Jia; Chu, Shuaishuai; Cui, Yin; Qian, Yue; Li, Xiuxiu; Xu, Fangxia; Shao, Xueming; Ma, Zhengliang; Xia, Tianjiao; Gu, Xiaoping

2018-04-13

Postoperative cognitive dysfunction (POCD) is a common clinical phenomenon characterized by cognitive deficits in patients after anesthesia and surgery. Advanced age is a significant independent risk factor for POCD. We previously reported that in young mice, sleep-wake rhythm is involved in the isoflurane-induced memory impairment. In present study, we sought to determine whether advanced age increased the risk of POCD through aggravated and prolonged post-anesthetic circadian disruption in the elderly. We constructed POCD model by submitting the mice to 5-h 1.3% isoflurane anesthesia from Zeitgeber Time (ZT) 14 to ZT19. Under novel object recognition assay (NOR) and Morris water maze (MWM) test, We found 5-h isoflurane anesthesia impaired the cognition of young mice for early 3 days after anesthesia but damaged the aged for at least 1 week. With Mini-Mitter continuously monitoring, a 3.22 ± 0.75 h gross motor activity acrophase delay was manifested in young mice on D1, while in the aged mice, the gross motor activity phase shift lasted for 3 days, consistent with the body temperature rhythm trends of change. Melatonin has been considered as an effective remedy for circadian rhythm shift. In aged mice, melatonin was pretreated intragastrically at the dose of 10 mg/kg daily for 7 consecutive days before anesthesia. We found that melatonin prevented isoflurane-induced cognitive impairments by restoring the locomotor activity and temperature circadian rhythm via clock gene resynchronization. Overall, these results indicated that Long-term isoflurane anesthesia induced more aggravated and prolonged memory deficits and circadian rhythms disruption in aged mice. Melatonin could prevent isoflurane-induced cognitive impairments by circadian rhythm resynchronization. Copyright © 2018. Published by Elsevier Inc.

Influence of experimental esophageal acidification on sleep bruxism: a randomized trial.

PubMed

Ohmure, H; Oikawa, K; Kanematsu, K; Saito, Y; Yamamoto, T; Nagahama, H; Tsubouchi, H; Miyawaki, S

2011-05-01

The aim of this cross-over, randomized, single-blinded trial was to examine whether intra-esophageal acidification induces sleep bruxism (SB). Polysomnography with electromyogram (EMG) of masseter muscle, audio-video recording, and esophageal pH monitoring were performed in a sleep laboratory. Twelve healthy adult males without SB participated. Intra-esophageal infusions of 5-mL acidic solution (0.1 N HCl) or saline were administered. The frequencies of EMG bursts, rhythmic masticatory muscle activity (RMMA) episodes, grinding noise, and the RMMA/microarousal ratio were significantly higher in the 20-minute period after acidic infusion than after saline infusion. RMMA episodes including SB were induced by esophageal acidification. This trial is registered with the UMIN Clinical Trials Registry, UMIN000002923. ASDA, American Sleep Disorders Association; EMG, electromyogram; GER, gastroesophageal reflux; LES, lower esophageal sphincter; NREM, non-rapid eye movement; REM, rapid eye movement; RMMA, rhythmic masticatory muscle activity; SB, sleep bruxism; SD, standard deviation; UES, upper esophageal sphincter.

The ontogeny of seizures induced by leucine-enkephalin and beta-endorphin.

PubMed

Snead, O C; Stephens, H

1984-06-01

Rats ranging in postnatal age from 6 hours to 28 days were implanted with cortical and depth electrodes as well as an indwelling cannula in the lateral ventricle. We then administered varying amounts of the opiate peptides leucine-enkephalin and beta-endorphin intracerebroventricularly with continuous electroencephalographic monitoring. Leucine-enkephalin produced electrical seizure activity in rats as young as 2 days. beta-Endorphin administration was associated with seizures at the fifth postnatal day, with a high incidence of apnea resulting in death in animals as young as 6 hours. An adult seizure response to beta-endorphin and leucine-enkephalin was seen at 15 and 28 days of age, respectively. Naloxone blocked the seizure produced by these opiate peptides in all age groups. The data indicate that the opiate peptides are potent epileptogenic compounds in developing brain, that seizures induced by leucine-enkephalin differ from those caused by beta-endorphin, and that petit mal-like seizure activity can be an adult response in the rodent.

Sensing the Environment Through Sestrins: Implications for Cellular Metabolism.

PubMed

Parmigiani, A; Budanov, A V

2016-01-01

Sestrins are a family of stress-responsive genes that have evolved to attenuate damage induced by stress caused to the cell. By virtue of their antioxidant activity, protein products of Sestrin genes prevent the accumulation of reactive oxygen species within the cell, thereby attenuating the detrimental effects of oxidative stress. In parallel, Sestrins participate in several signaling pathways that control the activity of the target of rapamycin protein kinase (TOR). TOR is a crucial sensor of intracellular and extracellular conditions that promotes cell growth and anabolism when nutrients and growth factors are abundant. In addition to reacting to stress-inducing insults, Sestrins also monitor the changes in the availability of nutrients, which allows them to serve as a key checkpoint for the TOR-regulated signaling pathways. In this review, we will discuss how Sestrins integrate signals from numerous stress- and nutrient-responsive signaling pathways to orchestrate cellular metabolism and support cell viability. Copyright © 2016 Elsevier Inc. All rights reserved.

Different types of theta rhythmicity are induced by social and fearful stimuli in a network associated with social memory.

PubMed

Tendler, Alex; Wagner, Shlomo

2015-02-16

Rhythmic activity in the theta range is thought to promote neuronal communication between brain regions. In this study, we performed chronic telemetric recordings in socially behaving rats to monitor electrophysiological activity in limbic brain regions linked to social behavior. Social encounters were associated with increased rhythmicity in the high theta range (7-10 Hz) that was proportional to the stimulus degree of novelty. This modulation of theta rhythmicity, which was specific for social stimuli, appeared to reflect a brain-state of social arousal. In contrast, the same network responded to a fearful stimulus by enhancement of rhythmicity in the low theta range (3-7 Hz). Moreover, theta rhythmicity showed different pattern of coherence between the distinct brain regions in response to social and fearful stimuli. We suggest that the two types of stimuli induce distinct arousal states that elicit different patterns of theta rhythmicity, which cause the same brain areas to communicate in different modes.

Integrated active mixing and biosensing using low frequency vibrating mixer and Love-wave sensor for real time detection of antibody binding event

NASA Astrophysics Data System (ADS)

Kardous, F.; El Fissi, L.; Friedt, J.-M.; Bastien, F.; Boireau, W.; Yahiaoui, R.; Manceau, J.-F.; Ballandras, S.

2011-05-01

The development of lab-on-chip devices is expected to dramatically change biochemical analyses, allowing for a notable increase of processing quality and throughput, provided the induced chemical reactions are well controlled. In this work, we investigate the impact of local acoustic mixing to promote or accelerate such biochemical reactions, such as antibody grafting on activated surfaces. During microarray building, the spotting mode leads to low efficiency in the ligand grafting and heterogeneities which limits its performances. To improve the transfer rate, we induce a hydrodynamic flow in the spotted droplet to disrupt the steady state during antibody grafting. To prove that acoustic mixing increases the antibody transfer rate to the biochip surface, we have used a Love-wave sensor allowing for real-time monitoring of the biological reaction for different operating conditions (with or without mixing). An analysis of the impact of the proposed mixing on grafting kinetics is proposed and finally checked in the case of antibody-antigen combination.

Zolpidem efficacy and safety in disorders of consciousness.

PubMed

Machado, Calixto; Estévez, Mario; Rodriguez-Rojas, Rafael

2018-01-01

Sutton and Clauss presented a detailed review about the effectiveness of zolpidem, discussing recoveries from brain damage due to strokes, trauma and hypoxia. A significant finding has been the unexpected and paradoxical increment of brain activity in vegetative state/unresponsive wakefulness syndrome (VS/UWS). On the contrary, zolpidem is considered one of the best sleep inducers in normal subjects. We have studied series of VS/UWS cases after zolpidem intake. We have demonstrated EEG activation, increment of BOLD signal in different brain regions, and an autonomic influence, mainly characterized by a vagolytic chronotropic effect without a significant increment of the vasomotor sympathetic tone. As this autonomic imbalance might induce cardio- circulatory complications, which we didn't find in any of our patients, we suggest developing future trials under control of physiological indices by bedside monitoring. However, considering that the paradoxical arousing zolpidem effect might be certainly related to brain function improvement, we agree with Sutton and Clauss that future multicentre and multinational clinical trials should be developed, but under control of physiological indices.

Induced phenylpropanoid metabolism during suberization and lignification: a comparative analysis

NASA Technical Reports Server (NTRS)

Bernards, M. A.; Susag, L. M.; Bedgar, D. L.; Anterola, A. M.; Lewis, N. G.

2000-01-01

Induction of the biosynthesis of phenylpropanoids was monitored at the enzyme level through measurement of the temporal change in the activity of two marker enzymes of phenylpropanoid metabolism, phenylalanine ammonia-lyase, (PAL, E.C. 4.1.3.5) and 4-coumaryl-CoA ligase (4-CL, E.C. 6.2.1.12) and two marker enzymes for hydroxycinnamyl alcohol biosynthesis, cinnamoyl-CoA:NADP+ oxidoreductase (CCR, E.C. 1.2.1.44) and cinnamyl alcohol dehydrogenase (CAD, E.C. 1.1.1.195) in both suberizing potato (Solanum tuberosum) tubers and lignifying loblolly pine (Pinus taeda) cell cultures. While measurable activities of PAL, 4-CL and CAD increased upon initiation of suberization in potato tubers, that of CCR did not. By contrast, all four enzymes were induced upon initiation of lignification in pine cell cultures. The lack of CCR induction in potato by wound treatment is consistent with the channelling of hydroxycinnamoyl-CoA derivatives away from monolignol formation and toward other hydroxycinnamoyl derivatives such as those that accumulate during suberization.

Routine physiotherapy does not induce a cardiorespiratory training effect post-stroke, regardless of walking ability.

PubMed

Kuys, Suzanne; Brauer, Sandra; Ada, Louise

2006-12-01

Cardiorespiratory fitness is increasingly being recognized as an impairment requiring physiotherapy intervention after stroke. The present study seeks to investigate if routine physiotherapy treatment is capable of inducing a cardiorespiratory training effect and if stroke patients attending physiotherapy who are unable to walk experience less cardiorespiratory stress during physiotherapy when compared to those who are able to walk. A descriptive, observational study, with heart rate monitoring and video-recording of physiotherapy rehabilitation, was conducted. Thirty consecutive stroke patients from a geriatric and rehabilitation unit of a tertiary metropolitan hospital, admitted for rehabilitation, and requiring physiotherapy were included in the study. The main measures of the study were duration (time) and intensity (percentage of heart rate reserve) of standing and walking activities during physiotherapy rehabilitation for non-walking and walking stroke patients. Stroke patients spent an average of 21 minutes participating in standing and walking activities that were capable of inducing a cardiorespiratory training effect. Stroke patients who were able to walk spent longer in these activities during physiotherapy rehabilitation than non-walking stroke patients (p < 0.05). An average intensity of 24% heart rate reserve (HRR) during standing and walking activities was insufficient to result in a cardiorespiratory training effect, with a maximum of 35% achieved for the stroke patients able to walk and 30% for those unable to walk. Routine physiotherapy rehabilitation had insufficient duration and intensity to result in a cardiorespiratory training effect in our group of stroke patients.

ABA-INSENSITIVE3, ABA-INSENSITIVE5, and DELLAs Interact to Activate the Expression of SOMNUS and Other High-Temperature-Inducible Genes in Imbibed Seeds in Arabidopsis[W

PubMed Central

Lim, Soohwan; Park, Jeongmoo; Lee, Nayoung; Jeong, Jinkil; Toh, Shigeo; Watanabe, Asuka; Kim, Junghyun; Kang, Hyojin; Kim, Dong Hwan; Kawakami, Naoto; Choi, Giltsu

2013-01-01

Seeds monitor the environment to germinate at the proper time, but different species respond differently to environmental conditions, particularly light and temperature. In Arabidopsis thaliana, light promotes germination but high temperature suppresses germination. We previously reported that light promotes germination by repressing SOMNUS (SOM). Here, we examined whether high temperature also regulates germination through SOM and found that high temperature activates SOM expression. Consistent with this, som mutants germinated more frequently than the wild type at high temperature. The induction of SOM mRNA at high temperature required abscisic acid (ABA) and gibberellic acid biosynthesis, and ABA-INSENSITIVE3 (ABI3), ABI5, and DELLAs positively regulated SOM expression. Chromatin immunoprecipitation assays indicated that ABI3, ABI5, and DELLAs all target the SOM promoter. At the protein level, ABI3, ABI5, and DELLAs all interact with each other, suggesting that they form a complex on the SOM promoter to activate SOM expression at high temperature. We found that high-temperature-inducible genes frequently have RY motifs and ABA-responsive elements in their promoters, some of which are targeted by ABI3, ABI5, and DELLAs in vivo. Taken together, our data indicate that ABI3, ABI5, and DELLAs mediate high-temperature signaling to activate the expression of SOM and other high-temperature-inducible genes, thereby inhibiting seed germination. PMID:24326588

The yeast Hot1 transcription factor is critical for activating a single target gene, STL1

PubMed Central

Bai, Chen; Tesker, Masha; Engelberg, David

2015-01-01

Transcription factors are commonly activated by signal transduction cascades and induce expression of many genes. They therefore play critical roles in determining the cell's fate. The yeast Hog1 MAP kinase pathway is believed to control the transcription of hundreds of genes via several transcription factors. To identify the bona fide target genes of Hog1, we inducibly expressed the spontaneously active variant Hog1D170A+F318L in cells lacking the Hog1 activator Pbs2. This system allowed monitoring the effects of Hog1 by itself. Expression of Hog1D170A+F318L in pbs2∆ cells imposed induction of just 105 and suppression of only 26 transcripts by at least twofold. We looked for the Hog1-responsive element within the promoter of the most highly induced gene, STL1 (88-fold). A novel Hog1 responsive element (HoRE) was identified and shown to be the direct target of the transcription factor Hot1. Unexpectedly, we could not find this HoRE in any other yeast promoter. In addition, the only gene whose expression was abolished in hot1∆ cells was STL1. Thus Hot1 is essential for transcription of just one gene, STL1. Hot1 may represent a class of transcription factors that are essential for transcription of a very few genes or even just one. PMID:25904326

Subcutaneous Administration of Low-Molecular-Weight Heparin to Horses Inhibits Ex Vivo Equine Herpesvirus Type 1-Induced Platelet Activation

PubMed Central

Stokol, Tracy; Serpa, Priscila B. S.; Brooks, Marjory B.; Divers, Thomas; Ness, Sally

2018-01-01

Equine herpesvirus type 1 (EHV-1) is a major cause of infectious respiratory disease, abortion and neurologic disease. Thrombosis in placental and spinal vessels and subsequent ischemic injury in EHV-1-infected horses manifests clinically as abortion and myeloencephalopathy. We have previously shown that addition of heparin anticoagulants to equine platelet-rich plasma (PRP) can abolish ex vivo EHV-1-induced platelet activation. The goal of this study was to test whether platelets isolated from horses treated with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) were resistant to ex vivo EHV-1-induced activation. In a masked, block-randomized placebo-controlled cross-over trial, 9 healthy adult horses received 4 subcutaneous injections at q. 12 h intervals of one of the following treatments: UFH (100 U/kg loading dose, 3 maintenance doses of 80 U/kg), 2 doses of LMWH (enoxaparin) 80 U/kg 24 h apart with saline at the intervening 12 h intervals, or 4 doses of saline. Blood samples were collected before treatment and after 36 h, 40 h (4 h after the last injection) and 60 h (24 h after the last injection). Two strains of EHV-1, Ab4 and RacL11, were added to PRP ex vivo and platelet membrane expression of P selectin was measured as a marker of platelet activation. Drug concentrations were monitored in a Factor Xa inhibition (anti-Xa) bioassay. We found that LMWH, but not UFH, inhibited platelet activation induced by low concentrations (1 × 106 plaque forming units/mL) of both EHV-1 strains at 40 h. At this time point, all horses had anti-Xa activities above 0.1 U/ml (range 0.15–0.48 U/ml) with LMWH, but not UFH. By 60 h, a platelet inhibitory effect was no longer detected and anti-Xa activity had decreased (range 0.03 to 0.07 U/ml) in LMWH-treated horses. Neither heparin inhibited platelet activation induced by high concentrations (5 × 106 plaque forming units/mL) of the RacL11 strain. We found substantial between horse variability in EHV-1-induced platelet activation at baseline and after treatment. Minor injection site reactions developed in horses given either heparin. These results suggest that LMWH therapy may prevent thrombotic sequelae of EHV-1, however further evaluation of dosage regimens is required. PMID:29892605

A neuroimaging study of conflict during word recognition.

PubMed

Riba, Jordi; Heldmann, Marcus; Carreiras, Manuel; Münte, Thomas F

2010-08-04

Using functional magnetic resonance imaging the neural activity associated with error commission and conflict monitoring in a lexical decision task was assessed. In a cohort of 20 native speakers of Spanish conflict was introduced by presenting words with high and low lexical frequency and pseudo-words with high and low syllabic frequency for the first syllable. Erroneous versus correct responses showed activation in the frontomedial and left inferior frontal cortex. A similar pattern was found for correctly classified words of low versus high lexical frequency and for correctly classified pseudo-words of high versus low syllabic frequency. Conflict-related activations for language materials largely overlapped with error-induced activations. The effect of syllabic frequency underscores the role of sublexical processing in visual word recognition and supports the view that the initial syllable mediates between the letter and word level.

Validation of biological activity testing procedure of recombinant human interleukin-7.

PubMed

Lutsenko, T N; Kovalenko, M V; Galkin, O Yu

2017-01-01

Validation procedure for method of monitoring the biological activity of reсombinant human interleukin-7 has been developed and conducted according to the requirements of national and international recommendations. This method is based on the ability of recombinant human interleukin-7 to induce proliferation of T lymphocytes. It has been shown that to control the biological activity of recombinant human interleukin-7 peripheral blood mononuclear cells (PBMCs) derived from blood or cell lines can be used. Validation charac­teristics that should be determined depend on the method, type of product or object test/measurement and biological test systems used in research. The validation procedure for the method of control of biological activity of recombinant human interleukin-7 in peripheral blood mononuclear cells showed satisfactory results on all parameters tested such as specificity, accuracy, precision and linearity.

Apomab, a fully human agonistic antibody to DR5, exhibits potent antitumor activity against primary and metastatic breast cancer

PubMed Central

Zinonos, Irene; Labrinidis, Agatha; Lee, Michelle; Liapis, Vasilios; Hay, Shelley; Ponomarev, Vladimir; Diamond, Peter; Zannettino, Andrew C.W.; Findlay, David M.; Evdokiou, Andreas

2017-01-01

Apomab, a fully human agonistic DR5 monoclonal antibody, triggers apoptosis through activation of the extrinsic apoptotic signaling pathway. In this study, we assessed the cytotoxic effect of Apomab in vitro and evaluated its antitumor activity in murine models of breast cancer development and progression. MDA-MB-231-TXSA breast cancer cells were transplanted into the mammary fat pad or directly into the tibial marrow cavity of nude mice. Apomab was administered early, postcancer cell transplantation, or after tumors progressed to an advanced stage. Tumor burden was monitored progressively using bioluminescence imaging, and the development of breast cancer–induced osteolysis was measured using micro-computed tomography. In vitro, Apomab treatment induced apoptosis in a panel of breast cancer cell lines but was without effect on normal human primary osteoblasts, fibroblasts, or mammary epithelial cells. In vivo, Apomab exerted remarkable tumor suppressive activity leading to complete regression of well-advanced mammary tumors. All animals transplanted with breast cancer cells directly into their tibiae developed large osteolytic lesions that eroded the cortical bone. In contrast, treatment with Apomab following an early treatment protocol inhibited both intraosseous and extraosseous tumor growth and prevented breast cancer–induced osteolysis. In the delayed treatment protocol, Apomab treatment resulted in the complete regression of advanced tibial tumors with progressive restoration of both trabecular and cortical bone leading to full resolution of osteolytic lesions. Apomab represents a potent immunotherapeutic agent with strong activity against the development and progression of breast cancer and should be evaluated in patients with primary and metastatic disease. PMID:19808976

Solar proton fluxes since 1956. [sunspot activity correlation

NASA Technical Reports Server (NTRS)

Reedy, R. C.

1977-01-01

The fluxes of protons emitted during solar flares since 1956 were evaluated. The depth-versus-activity profiles of Co-56 in several lunar rocks are consistent with the solar proton fluxes detected by experiments on several satellites. Only about 20% of the solar-proton-induced activities of Na-22 and Fe-55 in lunar rocks from early Apollo missions were produced by protons emitted from the sun during solar cycle 20 (1965-1975). The depth-versus-activity data for these radionuclides in several lunar rocks were used to determine the fluxes of protons during solar cycle 19 (1954-1964). The average proton fluxes for cycle 19 are about five times those for both the last million years and for cycle 20 and are about five times the previous estimate for cycle 19 based on neutron-monitor and radio ionospheric measurements. These solar-proton flux variations correlate with changes in sunspot activity.

Imaging Neural Activity Using Thy1-GCaMP Transgenic mice

PubMed Central

Chen, Qian; Cichon, Joseph; Wang, Wenting; Qiu, Li; Lee, Seok-Jin R.; Campbell, Nolan R.; DeStefino, Nicholas; Goard, Michael J.; Fu, Zhanyan; Yasuda, Ryohei; Looger, Loren L.; Arenkiel, Benjamin R.; Gan, Wen-Biao; Feng, Guoping

2014-01-01

Summary The ability to chronically monitor neuronal activity in the living brain is essential for understanding the organization and function of the nervous system. The genetically encoded green fluorescent protein based calcium sensor GCaMP provides a powerful tool for detecting calcium transients in neuronal somata, processes, and synapses that are triggered by neuronal activities. Here we report the generation and characterization of transgenic mice that express improved GCaMPs in various neuronal subpopulations under the control of the Thy1 promoter. In vitro and in vivo studies show that calcium transients induced by spontaneous and stimulus-evoked neuronal activities can be readily detected at the level of individual cells and synapses in acute brain slices, as well as chronically in awake behaving animals. These GCaMP transgenic mice allow investigation of activity patterns in defined neuronal populations in the living brain, and will greatly facilitate dissecting complex structural and functional relationships of neural networks. PMID:23083733

Diagnosis of anticholinesterase poisoning in birds: Effects of environmental temperature and underfeeding on cholinesterase activity

USGS Publications Warehouse

Rattner, B.A.

1982-01-01

Brain cholinesterase (ChE) activity has been used extensively to monitor exposure to organophosphorus (OP) and carbamate (CB) insecticides in wild birds. A series of factorial experiments was conducted to assess the extent to which noncontaminant-related environmental conditions might affect brain ChE activity and thereby confound the diagnosis of OP and CB intoxication. Underfeeding (restricting intake to 50% of control for 21 d or fasting for 1-3 d) or exposure to elevated temperature (36 + 1?C for 1 d) caused only slight reductions (10-17%) in brain AChE activity in adult male Japanese quail (Coturnix coturnix japonica). This degree of 'reduction' in brain AChE activity is considerably less than the 50% 'inhibition' criterion employed in the diagnosis of insecticide-induced mortality, but nevertheless approaches the 20% 'inhibition' level used as a conservative estimate of sublethal exposure to a known insecticide application.

Thioredoxin-mimetic peptide CB3 lowers MAPKinase activity in the Zucker rat brain☆

PubMed Central

Cohen-Kutner, Moshe; Khomsky, Lena; Trus, Michael; Ben-Yehuda, Hila; Lenhard, James M.; Liang, Yin; Martin, Tonya; Atlas, Daphne

2014-01-01

Diabetes is a high risk factor for dementia. High glucose may be a risk factor for dementia even among persons without diabetes, and in transgenic animals it has been shown to cause a potentiation of indices that are pre-symptomatic of Alzheimer's disease. To further elucidate the underlying mechanisms linking inflammatory events elicited in the brain during oxidative stress and diabetes, we monitored the activation of mitogen-activated kinsase (MAPKs), c-jun NH2-terminal kinase (JNK), p38 MAP kinases (p38MAPK), and extracellular activating kinsae1/2 (ERK1/2) and the anti-inflammatory effects of the thioredoxin mimetic (TxM) peptides, Ac-Cys-Pro-Cys-amide (CB3) and Ac-Cys-Gly-Pro-Cys-amide (CB4) in the brain of male leptin-receptor-deficient Zucker diabetic fatty (ZDF) rats and human neuroblastoma SH-SY5Y cells. Daily i.p. injection of CB3 to ZDF rats inhibited the phosphorylation of JNK and p38MAPK, and prevented the expression of thioredoxin-interacting-protein (TXNIP/TBP-2) in ZDF rat brain. Although plasma glucose/insulin remained high, CB3 also increased the phosphorylation of AMP-ribose activating kinase (AMPK) and inhibited p70S6K kinase in the brain. Both CB3 and CB4 reversed apoptosis induced by inhibiting thioredoxin reductase as monitored by decreasing caspase 3 cleavage and PARP dissociation in SH-SY5Y cells. The decrease in JNK and p38MAPK activity in the absence of a change in plasma glucose implies a decrease in oxidative or neuroinflammatory stress in the ZDF rat brain. CB3 not only attenuated MAPK phosphorylation and activated AMPK in the brain, but it also diminished apoptotic markers, most likely acting via the MAPK–AMPK–mTOR pathway. These results were correlated with CB3 and CB4 inhibiting inflammation progression and protection from oxidative stress induced apoptosis in human neuronal cells. We suggest that by attenuating neuro-inflammatory processes in the brain Trx1 mimetic peptides could become beneficial for preventing neurological disorders associated with diabetes. PMID:24624334

Glia-derived signals induce synapse formation in neurones of the rat central nervous system

PubMed Central

Nägler, Karl; Mauch, Daniela H; Pfrieger, Frank W

2001-01-01

To study the effects of glial cells on synapse formation, we established microcultures of purified rat retinal ganglion cells (RGCs) and monitored synapse (autapse) development in single neurones using electrophysiological recordings, FM1-43 labelling and immunocytochemistry.Solitary neurones grew ramifying neurites, but formed only very few and inefficient excitatory autapses, when cultured for up to 2 weeks in defined medium and in the absence of glial cells.Treatment of glia-free microcultures of RGCs with glia-conditioned medium (GCM) increased the number of autapses per neurone by up to 10-fold. This was indicated by a similar increase in the frequency of spontaneous events and the number of FM1-43-labelled functional release sites and of puncta, where pre- and postsynaptic markers colocalized.In addition, GCM treatment enhanced the efficacy of presynaptic transmitter release as indicated by lower failure rates of stimulation-induced excitatory autaptic currents, a 200-fold increase in the frequency of asynchronous release and an accelerated stimulation-induced FM1-43 destaining. Furthermore, GCM induced an increase in the quantal size.GCM affected autaptic activity not immediately, but with a delay of 24 h, and the effects on stimulation-induced autaptic currents occurred before changes in the frequency of spontaneous events indicating an early strengthening of existing autapses followed by a later increase in autapse number.The observed effects were mediated by proteinase K-sensitive factors in GCM and occurred independently of electrical activity.These results suggest that soluble glia-derived signals induce synapse formation and maturation in neurones of the central nervous system (CNS). PMID:11410625

Non-invasive monitoring of pulmonary artery pressure from timing information by EIT: experimental evaluation during induced hypoxia.

PubMed

Proença, Martin; Braun, Fabian; Solà, Josep; Adler, Andy; Lemay, Mathieu; Thiran, Jean-Philippe; Rimoldi, Stefano F

2016-06-01

Monitoring of pulmonary artery pressure (PAP) in pulmonary hypertensive patients is currently limited to invasive solutions. We investigate a novel non-invasive approach for continuous monitoring of PAP, based on electrical impedance tomography (EIT), a safe, low-cost and non-invasive imaging technology. EIT recordings were performed in three healthy subjects undergoing hypoxia-induced PAP variations. The pulmonary pulse arrival time (PAT), a timing parameter physiologically linked to the PAP, was automatically calculated from the EIT signals. Values were compared to systolic PAP values from Doppler echocardiography, and yielded strong correlation scores ([Formula: see text]) for all three subjects. Results suggest the feasibility of non-invasive, unsupervised monitoring of PAP.

Monitoring the bio-stimulation of hydrocarbon-contaminated soils by measurements of soil electrical properties, and CO2 content and its 13C/12C isotopic signature

NASA Astrophysics Data System (ADS)

Noel, C.; Gourry, J.; Ignatiadis, I.; Colombano, S.; Dictor, M.; Guimbaud, C.; Chartier, M.; Dumestre, A.; Dehez, S.; Naudet, V.

2013-12-01

Hydrocarbon contaminated soils represent an environmental issue as it impacts on ecosystems and aquifers. Where significant subsurface heterogeneity exists, conventional intrusive investigations and groundwater sampling can be insufficient to obtain a robust monitoring of hydrocarbon contaminants, as the information they provide is restricted to vertical profiles at discrete locations, with no information between sampling points. In order to obtain wider information in space volume on subsurface modifications, complementary methods can be used like geophysics. Among geophysical methods, geoelectrical techniques such as electrical resistivity (ER) and induced polarization (IP) seem the more promising, especially to study the effects of biodegradation processes. Laboratory and field geoelectrical experiments to characterize soils contaminated by oil products have shown that mature hydrocarbon-contaminated soils are characterized by enhanced electrical conductivity although hydrocarbons are electrically resistive. This high bulk conductivity is due to bacterial impacts on geological media, resulting in changes in the chemical and physical properties and thus, to the geophysical properties of the ground. Moreover, microbial activity induced CO2 production and isotopic deviation of carbon. Indeed, produced CO2 will reflect the pollutant isotopic signature. Thus, the ratio δ13C(CO2) will come closer to δ13C(hydrocarbon). BIOPHY, project supported by the French National Research Agency (ANR), proposes to use electrical methods and gas analyses to develop an operational and non-destructive method for monitoring in situ biodegradation of hydrocarbons in order to optimize soil treatment. Demonstration field is located in the South of Paris (France), where liquid fuels (gasoline and diesel) leaked from some tanks in 1997. In order to stimulate biodegradation, a trench has been dug to supply oxygen to the water table and thus stimulate aerobic metabolic bioprocesses. ER and IP surveys are performed regularly to monitor the stimulated biodegradation and progress of remediation until soil cleanup. Microbial activity is characterized by CO2 production increase and δ13C isotopic deviation, in the produced CO2 measured by infrared laser spectroscopy, and by an evolution of electrical conductivity and IP responses in correlation with microbiological and chemical analyses.