Assessment of SWE data assimilation for ensemble streamflow predictions

NASA Astrophysics Data System (ADS)

Franz, Kristie J.; Hogue, Terri S.; Barik, Muhammad; He, Minxue

2014-11-01

An assessment of data assimilation (DA) for Ensemble Streamflow Prediction (ESP) using seasonal water supply hindcasting in the North Fork of the American River Basin (NFARB) and the National Weather Service (NWS) hydrologic forecast models is undertaken. Two parameter sets, one from the California Nevada River Forecast Center (RFC) and one from the Differential Evolution Adaptive Metropolis (DREAM) algorithm, are tested. For each parameter set, hindcasts are generated using initial conditions derived with and without the inclusion of a DA scheme that integrates snow water equivalent (SWE) observations. The DREAM-DA scenario uses an Integrated Uncertainty and Ensemble-based data Assimilation (ICEA) framework that also considers model and parameter uncertainty. Hindcasts are evaluated using deterministic and probabilistic forecast verification metrics. In general, the impact of DA on the skill of the seasonal water supply predictions is mixed. For deterministic (ensemble mean) predictions, the Percent Bias (PBias) is improved with integration of the DA. DREAM-DA and the RFC-DA have the lowest biases and the RFC-DA has the lowest Root Mean Squared Error (RMSE). However, the RFC and DREAM-DA have similar RMSE scores. For the probabilistic predictions, the RFC and DREAM have the highest Continuous Ranked Probability Skill Scores (CRPSS) and the RFC has the best discrimination for low flows. Reliability results are similar between the non-DA and DA tests and the DREAM and DREAM-DA have better reliability than the RFC and RFC-DA for forecast dates February 1 and later. Despite producing improved streamflow simulations in previous studies, the hindcast analysis suggests that the DA method tested may not result in obvious improvements in streamflow forecasts. We advocate that integration of hindcasting and probabilistic metrics provides more rigorous insight on model performance for forecasting applications, such as in this study.

Modeling Fast-scan Cyclic Voltammetry Data from Electrically Stimulated Dopamine Neurotransmission Data Using QNsim1.0.

PubMed

Harun, Rashed; Grassi, Christine M; Munoz, Miranda J; Wagner, Amy K

2017-06-05

Central dopaminergic (DAergic) pathways have an important role in a wide range of functions, such as attention, motivation, and movement. Dopamine (DA) is implicated in diseases and disorders including attention deficit hyperactivity disorder, Parkinson's disease, and traumatic brain injury. Thus, DA neurotransmission and the methods to study it are of intense scientific interest. In vivo fast-scan cyclic voltammetry (FSCV) is a method that allows for selectively monitoring DA concentration changes with fine temporal and spatial resolution. This technique is commonly used in conjunction with electrical stimulations of ascending DAergic pathways to control the impulse flow of dopamine neurotransmission. Although the stimulated DA neurotransmission paradigm can produce robust DA responses with clear morphologies, making them amenable for kinetic analysis, there is still much debate on how to interpret the responses in terms of their DA release and clearance components. To address this concern, a quantitative neurobiological (QN) framework of stimulated DA neurotransmission was recently developed to realistically model the dynamics of DA release and reuptake over the course of a stimulated DA response. The foundations of this model are based on experimental data from stimulated DA neurotransmission and on principles of neurotransmission adopted from various lines of research. The QN model implements 12 parameters related to stimulated DA release and reuptake dynamics to model DA responses. This work describes how to simulate DA responses using QNsim1.0 and also details principles that have been implemented to systematically discern alterations in the stimulated dopamine release and reuptake dynamics.

Dopamine-functionalized InP/ZnS quantum dots as fluorescence probes for the detection of adenosine in microfluidic chip.

PubMed

Ankireddy, Seshadri Reddy; Kim, Jongsung

2015-01-01

Microbeads are frequently used as solid supports for biomolecules such as proteins and nucleic acids in heterogeneous microfluidic assays. Chip-based, quantum dot (QD)-bead-biomolecule probes have been used for the detection of various types of DNA. In this study, we developed dopamine (DA)-functionalized InP/ZnS QDs (QDs-DA) as fluorescence probes for the detection of adenosine in microfluidic chips. The photoluminescence (PL) intensity of the QDs-DA is quenched by Zn(2+) because of the strong coordination interactions. In the presence of adenosine, Zn(2+) cations preferentially bind to adenosine, and the PL intensity of the QDs-DA is recovered. A polydimethylsiloxane-based microfluidic chip was fabricated, and adenosine detection was confirmed using QDs-DA probes.

Dopamine-functionalized InP/ZnS quantum dots as fluorescence probes for the detection of adenosine in microfluidic chip

PubMed Central

Ankireddy, Seshadri Reddy; Kim, Jongsung

2015-01-01

Microbeads are frequently used as solid supports for biomolecules such as proteins and nucleic acids in heterogeneous microfluidic assays. Chip-based, quantum dot (QD)-bead-biomolecule probes have been used for the detection of various types of DNA. In this study, we developed dopamine (DA)-functionalized InP/ZnS QDs (QDs-DA) as fluorescence probes for the detection of adenosine in microfluidic chips. The photoluminescence (PL) intensity of the QDs-DA is quenched by Zn2+ because of the strong coordination interactions. In the presence of adenosine, Zn2+ cations preferentially bind to adenosine, and the PL intensity of the QDs-DA is recovered. A polydimethylsiloxane-based microfluidic chip was fabricated, and adenosine detection was confirmed using QDs-DA probes. PMID:26347351

Using Dynamic Assessment to Evaluate the Expressive Syntax of Children who use Augmentative and Alternative Communication

PubMed Central

King, Marika R.; Binger, Cathy; Kent-Walsh, Jennifer

2015-01-01

The developmental readiness of four 5-year-old children to produce basic sentences using graphic symbols on an augmentative and alternative communication (AAC) device during a dynamic assessment (DA) task was examined. Additionally, the ability of the DA task to predict performance on a subsequent experimental task was evaluated. A graduated prompting framework was used during DA. Measures included amount of support required to produce the targets, modifiability (change in participant performance) within a DA session, and predictive validity of DA. Participants accurately produced target structures with varying amounts of support. Modifiability within DA sessions was evident for some participants, and partial support was provided for the measures of predictive validity. These initial results indicate that DA may be a viable way to measure young children’s developmental readiness to learn how to sequence simple, rule-based messages via aided AAC. PMID:25621928

Use of electronic dietary assessment tools in primary care: an interdisciplinary perspective.

PubMed

Bonilla, Carolina; Brauer, Paula; Royall, Dawna; Keller, Heather; Hanning, Rhona M; DiCenso, Alba

2015-02-25

Dietary assessment can be challenging for many reasons, including the wide variety of foods, eating patterns and nutrients to be considered. In team-based primary care practice, various disciplines may be involved in assessing diet. Electronic-based dietary assessment (e-DA) instruments available now through mobile apps or websites can potentially facilitate dietary assessment. Providers views of facilitators and barriers related to e-DA instruments and their recommendations for improvement can inform the further development of these tools. The objective of this study was to explore provider perspectives on e-DA tools in mobile apps and websites. The exploratory sequential mixed methods design included interdisciplinary focus groups followed by a web-based survey sent to Family Health Teams throughout Ontario, Canada. Descriptive and bivariate analyses were completed. Focus group transcripts contributed to web-survey content, while interpretive themes added depth and context. 11 focus groups with 50 providers revealed varying perspectives on the use of e-DA for: 1) improving patients' eating habits; 2) improving the quality of dietary assessment; and, 3) integrating e-DA into the care process. In the web-survey 191 respondents from nine disciplines in 73 FHTs completed the survey. Dietitians reported greater use of e-DA than other providers (63% vs.19%; p = .000) respectively. There was strong interest among disciplines in the use of e-DA tools for the management of obesity, diabetes and heart disease, especially for patient self-monitoring. Barriers identified were: patients' lack of comfort with using technology, misinterpretation of e-DA results by patients, time and education for providers to interpret results, and time for providers to offer counselling. e-DA tools in mobile apps and websites may improve dietary counselling over time. Addressing the identified facilitators and barriers can potentially promote the uptake of e-DA into clinical practice.

Pyrrole-phenylboronic acid: a novel monomer for dopamine recognition and detection based on imprinted electrochemical sensor.

PubMed

Zhong, Min; Teng, Ying; Pang, Shufen; Yan, Liqin; Kan, Xianwen

2015-02-15

A molecular imprinting polymer (MIP) based electrochemical sensor was successfully prepared for dopamine (DA) recognition and detection using pyrrole-phenylboronic acid (py-PBA) as a novel electropolymerized monomer. py-PBA could form cyclic boronic ester bond with DA, thus endowing a double recognition capacity of the sensor to DA in the combination of the imprinted effect of MIP. Compared with the sensor prepared using pyrrole or phenylboronic acid as electropolymerized monomer, the present sensor exhibited a remarkable high imprinted factor to DA. The influence factors including pH value, the mole ratio between monomer and template molecule, electropolymerization scan rate, and scan cycles of electropolymerization process were investigated and optimized. Under the optimal conditions, the sensor could recognize DA from its analogs and monosaccharides. A linear ranging from 5.0 × 10(-8) to 1.0 × 10(-5) mol/L for the detection of DA was obtained with a detection limit of 3.3 × 10(-8) mol/L (S/N = 3). The sensor has been applied to analyze DA in injection samples with satisfactory results. Copyright © 2014 Elsevier B.V. All rights reserved.

Controller evaluations of the descent advisor automation aid

NASA Technical Reports Server (NTRS)

Tobias, Leonard; Volckers, Uwe; Erzberger, Heinz

1989-01-01

An automation aid to assist air traffic controllers in efficiently spacing traffic and meeting arrival times at a fix has been developed at NASA Ames Research Center. The automation aid, referred to as the descent advisor (DA), is based on accurate models of aircraft performance and weather conditions. The DA generates suggested clearances, including both top-of-descent point and speed profile data, for one or more aircraft in order to achieve specific time or distance separation objectives. The DA algorithm is interfaced with a mouse-based, menu-driven controller display that allows the air traffic controller to interactively use its accurate predictive capability to resolve conflicts and issue advisories to arrival aircraft. This paper focuses on operational issues concerning the utilization of the DA, specifically, how the DA can be used for prediction, intrail spacing, and metering. In order to evaluate the DA, a real time simulation was conducted using both current and retired controller subjects. Controllers operated in teams of two, as they do in the present environment; issues of training and team interaction will be discussed. Evaluations by controllers indicated considerable enthusiasm for the DA aid, and provided specific recommendations for using the tool effectively.

Deciding how many embryos to transfer after in vitro fertilisation: development and pilot test of a decision aid.

PubMed

van Peperstraten, Arno M; Hermens, Rosella P M G; Nelen, Willianne L D M; Stalmeier, Peep F M; Wetzels, Alex M M; Maas, Pettie H M; Kremer, Jan A M; Grol, Richard P T M

2010-01-01

When deciding how many embryos to transfer during in vitro fertilisation (IVF), clinicians and patients have to balance optimizing the chance of pregnancy against preventing multiple pregnancies and the associated complications. This paper describes the development and pilot test of a patient decision aid (DA) for this purpose. The development of the DA consisted of a literature search, establishment of the format, and a pilot test among IVF patients. The DA development was supervised by a panel of experts in the fields of subfertility, obstetrics and DA-research and it was based on the criteria of the International Patient Decision Aid Standards. One Cochrane review and 34 articles were selected for the DA content. The DA presents information in text, summaries, tables, figures and through an interactive worksheet. The DA was reviewed positively and as acceptable for use in clinical practice by patients and professionals. The DA was thoroughly developed and is likely to be helpful for the decision-making process for the number of embryos transferred after IVF. Physicians and researchers can use the DA without restriction in clinical practice or research related to decision-making.

Combined Application of UHPLC-QTOF/MS, HPLC-ELSD and 1 H-NMR Spectroscopy for Quality Assessment of DA-9801, A Standardised Dioscorea Extract.

PubMed

Kang, Kyo Bin; Ryu, Jayoung; Cho, Youngwoong; Choi, Sang-Zin; Son, Miwon; Sung, Sang Hyun

2017-05-01

DA-9801, a standardised 50% aqueous ethanolic extract of a mixture of Dioscorea japonica and D. nipponica, is a botanical drug candidate for the treatment of diabetic neuropathy, which finished its US phase II clinical trials recently. An advanced quality control method is needed for further development of DA-9801, considering its high contents of both primary and secondary metabolites. Development of a quality assessment strategy for DA-9801, based on the combination of UHPLC-QTOF/MS, HPLC-ELSD, and 1 H-NMR spectroscopy. The method was developed and tested with 15 batch products of DA-9801. The steroidal saponins of DA-9801 were tentatively identified by UHPLC-QTOF/MS and were quantified with the validated HPLC-ELSD method. Primary metabolites of DA-9801 were identified and profiled using 1 H-NMR spectrometry. The batch-to-batch equivalence of DA-9801 was tested with the 1 H-NMR spectra using spectral binning, correlation analysis, and principal component analysis. Six major saponins of DA-9801 were tentatively identified by UHPLC-QTOF/MS. Among them, protodioscin and dioscin were quantified by the validated HPLC-ELSD method. Twenty-six metabolites were identified in 1 H-NMR spectra. The similarity between DA-9801 batches could be evaluated with the NMR spectra of DA-9801. The 1 H-NMR method also revealed that two Dioscorea species contributed distinct amino acids to the contents of DA-9801. This study validates the effectiveness of UHPLC-QTOF/MS, HPLC-ELSD, and 1 H NMR-combined method for quality control of DA-9801 and its crude materials. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Design of New Bridge-Ring Energetic Compounds Obtained by Diels-Alder Reactions of Tetranitroethylene Dienophile.

PubMed

He, Piao; Mei, Hao-Zheng; Wu, Le; Yang, Jun-Qing; Zhang, Jian-Guo; Cohen, Adva; Gozin, Michael

2018-03-29

The density functional theory method was employed to calculate three-dimensional structures for a series of novel explosophores. The design of new molecules (DA1-DA12) was based on the bridge-ring structures that could be formed via Diels-Alder (DA) reaction of selected nitrogen-rich dienes and tetranitroethylene dienophile. The feasibility of the proposed DA reactions was predicted on the basis of the molecular orbital theory. The strong interactions between the HOMO of dienes, with electron-donating groups (Diene2, Diene6, and Diene8), and the LUMO of tetranitroethylene dienophile suggested thermodynamically favorable formation of the desired DA reaction products. In addition to molecular structures of the explored DA compounds, their physicochemical and energetic properties were also calculated in detail. Due to compact bridge-ring structures, new energetic molecules have highly positive heats of formation (up to 1124.90 kJ·mol -1 ) and high densities (up to 2.04 g·cm -3 ). Also, as a result of all-right ratios of nitrogen and oxygen, most of the new compounds possess high detonation velocities (8.28-10.02 km·s -1 ) and high detonation pressures (30.87-47.83 GPa). Energetic compounds DA1, DA4, and DA12 exhibit a superior detonation performance over widely used HMX explosive, and DA5, DA7, and DA10 could be comparable to the state-of-the-art CL-20 and ONC explosives. Our proposed designs and synthetic methodology should provide a platform for the development of novel energetic materials with superior performance.

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

Huh, S; Lee, S; Dagan, R

Purpose: To investigate the feasibility of utilizing Dynamic Arc (DA) and IMRT with 5mm MLC leaf of VERO treatment unit for SRS/FSRT brain cancer patients with non-invasive stereotactic treatments. The DA and IMRT plans using the VERO unit (BrainLab Inc, USA) are compared with cone-based planning and proton plans to evaluate their dosimetric advantages. Methods: The Vero treatment has unique features like no rotational or translational movements of the table during treatments, Dynamic Arc/IMRT, tracking of IR markers, limitation of Ring rotation. Accuracies of the image fusions using CBCT, orthogonal x-rays, and CT are evaluated less than ∼ 0.7mm withmore » a custom-made target phantom with 18 hidden targets. 1mm margin is given to GTV to determine PTV for planning constraints considering all the uncertainties of planning computer and mechanical uncertainties of the treatment unit. Also, double-scattering proton plans with 6F to 9F beams and typical clinical parameters, multiple isocenter plans with 6 to 21 isocenters, and DA/IMRT plans are evaluated to investigate the dosimetric advantages of the DA/IMRT for complex shape of targets. Results: 3 Groups of the patients are divided: (1) Group A (complex target shape), CI's are same for IMRT, and DGI of the proton plan are better by 9.5% than that of the IMRT, (2) Group B, CI of the DA plans (1.91+/−0.4) are better than cone-based plan, while DGI of the DA plan is 4.60+/−1.1 is better than cone-based plan (5.32+/−1.4), (3) Group C (small spherical targets), CI of the DA and cone-based plans are almost the same. Conclusion: For small spherical targets, cone-based plans are superior to other 2 plans: DS proton and DA plans. For complex or irregular plans, dynamic and IMRT plans are comparable to cone-based and proton plans for complex targets.« less

Recyclable thermosetting thermal pad using silicone-based polyurethane crosslinked by Diels-Alder adduct

NASA Astrophysics Data System (ADS)

Kim, Jong-Woong; Lee, Da Hee; Jeon, Hee-Jeong; Jang, Sung Il; Cho, Hyun Min; Kim, Youngmin

2018-01-01

The recyclable silicone-based thermoset was successfully synthesized by making use of a Diels-Alder (DA) adduct as a cross-linker. The incorporation of the furan-tethered diol 1 into the polymer backbones realized the crosslinking of polymers via the DA reaction. The thermosetting polymer was dissolved in DMF after the retro DA reaction which was monitored by 1H NMR spectroscopy. Due to the retro DA reaction, polymer showed the mendable behavior when it was scratched followed by being heated. This polymer was mixed with alumina powders to fabricate the thermal pad. The thermal resistance of this pad was measured to be 0.48 K/W by a thermal transient test. The thermosetting composite was recycled via the retro DA reaction. The thermal resistance of the recycled one was similar to that of the original one.

da Vinci decoded: does da Vinci stereopsis rely on disparity?

PubMed

Tsirlin, Inna; Wilcox, Laurie M; Allison, Robert S

2012-11-01

In conventional stereopsis, the depth between two objects is computed based on the retinal disparity in the position of matching points in the two eyes. When an object is occluded by another object in the scene, so that it is visible only in one eye, its retinal disparity cannot be computed. Nakayama and Shimojo (1990) found that a precept of quantitative depth between the two objects could still be established for such stimuli and proposed that this precept is based on the constraints imposed by occlusion geometry. They named this and other occlusion-based depth phenomena "da Vinci stereopsis." Subsequent research found quantitative depth based on occlusion geometry in several other classes of stimuli grouped under the term da Vinci stereopsis. However, Nakayama and Shimojo's findings were later brought into question by Gillam, Cook, and Blackburn (2003), who suggested that quantitative depth in their stimuli was perceived based on conventional disparity. In order to understand whether da Vinci stereopsis relies on one type of mechanism or whether its function is stimulus dependent we examine the nature and source of depth in the class of stimuli used by Nakayama and Shimojo (1990). We use three different psychophysical and computational methods to show that the most likely source for depth in these stimuli is occlusion geometry. Based on these experiments and previous data we discuss the potential mechanisms responsible for processing depth from monocular features in da Vinci stereopsis.

Dopamine efflux in the nucleus accumbens during within-session extinction, outcome-dependent, and habit-based instrumental responding for food reward.

PubMed

Ahn, Soyon; Phillips, Anthony G

2007-04-01

Dopamine (DA) activity in the nucleus accumbens (NAc) is related to the general motivational effects of rewarding stimuli. Dickinson and colleagues have shown that initial acquisition of instrumental responding reflects action-outcome relationships based on instrumental incentive learning, which establishes the value of an outcome. Given that the sensitivity of responding to outcome devaluation is not affected by NAc lesions, it is unlikely that incentive learning during the action-outcome phase is mediated by DA activity in the NAc. DA efflux in the NAc after limited and extended training was compared on the assumption that comparable changes would be observed during both action-outcome- and habit-based phases of instrumental responding for food. This study also tested the hypothesis that increase in NAc DA activity is correlated with instrumental responding during extinction maintained by a conditioned stimulus paired with food. Rats were trained to lever press for food (random-interval 30 s schedule). On the 5th and 16th day of training, microdialysis samples were collected from the NAc or mediodorsal striatum (a control site for generalized activity) during instrumental responding in extinction and then for food reward, and analyzed for DA content using high performance liquid chromatography. Increase in DA efflux in the NAc accompanied responding for food pellets on both days 5 and 16, with the magnitude of increase significantly enhanced on day 16. DA efflux was also significantly elevated during responding in extinction only on day 16. These results support a role for NAc DA activity in Pavlovian, but not instrumental, incentive learning.

Intranasal Dopamine Reduces In Vivo [(123)I]FP-CIT Binding to Striatal Dopamine Transporter: Correlation with Behavioral Changes and Evidence for Pavlovian Conditioned Dopamine Response.

PubMed

de Souza Silva, Maria A; Mattern, Claudia; Decheva, Cvetana; Huston, Joseph P; Sadile, Adolfo G; Beu, Markus; Müller, H-W; Nikolaus, Susanne

2016-01-01

Dopamine (DA), which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA), nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT) binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [(123)I]FP-CIT to the DAT should be decreased due to competition at the receptor. Rats were administered 3 mg/kg IN-DA and vehicle (VEH), with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming) were assessed for 30 min in an open field prior to administration of [(123)I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT 2 h following administration of the radioligand. (1) After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered DA had central action and increased DA levels comparable to that found previously with L-DOPA administration; and (2) DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased) the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant drugs. (a) demonstrate a direct central action of intranasally applied DA on the DAT in the dorsal striatum, indicating enhanced DA availability; and (b) provide first evidence of a Pavlovian conditioned DA response at the DAT. The latter results have relevance to understanding neurochemical mechanisms that underlie placebo action in the treatment of Parkinsonian patients.

A Novel Decision Aid to Support Informed Decision-Making Process in Patients with a Symptomatic Nonlower Pole Renal Stone <20 mm in Diameter.

PubMed

Gökce, Mehmet İlker; Esen, Barış; Sancı, Adem; Akpınar, Cağrı; Süer, Evren; Gülpınar, Ömer

2017-07-01

Stone disease is an important health problem, and patients have different treatment choices. Shared decision making is recommended for deciding the treatment type, but patient education is necessary. Decision aids (DAs) are used for this aim, and herein, we developed a novel DA for patients with symptomatic nonlower pole renal stones <20 mm in diameter. The DA development process was established based on the recommended guides. General characteristics of the stone disease and details of the shockwave lithotripsy and retrograde intrarenal surgery were included in the content of the DA. The DA was further revised based on the suggestions of different physician groups and patients. The DA was evaluated by three physicians (Delphi assessment-International Patient Decision Aid Standards [IPDAS] Collaboration standards) and 25 patients (questionnaire of six questions with five-point Likert scale). The DA was designed as a booklet, and Delphi group assessment resulted in a total score of 50/54. Patient evaluation of the DA resulted in favorable outcomes, and patients generally recommended its use by other patients. This novel DA for patients with a symptomatic nonlower pole renal stone <20 mm showed promising results and was well accepted by the patients. We believe that this DA will have a positive impact on patients' level of knowledge. Increased level of knowledge will also improve the patients' contribution to the shared decision-making process. A further prospective randomized trial to compare with the standard patient informing process is also planned.

Contribution of synchronized GABAergic neurons to dopaminergic neuron firing and bursting.

PubMed

Morozova, Ekaterina O; Myroshnychenko, Maxym; Zakharov, Denis; di Volo, Matteo; Gutkin, Boris; Lapish, Christopher C; Kuznetsov, Alexey

2016-10-01

In the ventral tegmental area (VTA), interactions between dopamine (DA) and γ-aminobutyric acid (GABA) neurons are critical for regulating DA neuron activity and thus DA efflux. To provide a mechanistic explanation of how GABA neurons influence DA neuron firing, we developed a circuit model of the VTA. The model is based on feed-forward inhibition and recreates canonical features of the VTA neurons. Simulations revealed that γ-aminobutyric acid (GABA) receptor (GABAR) stimulation can differentially influence the firing pattern of the DA neuron, depending on the level of synchronization among GABA neurons. Asynchronous activity of GABA neurons provides a constant level of inhibition to the DA neuron and, when removed, produces a classical disinhibition burst. In contrast, when GABA neurons are synchronized by common synaptic input, their influence evokes additional spikes in the DA neuron, resulting in increased measures of firing and bursting. Distinct from previous mechanisms, the increases were not based on lowered firing rate of the GABA neurons or weaker hyperpolarization by the GABAR synaptic current. This phenomenon was induced by GABA-mediated hyperpolarization of the DA neuron that leads to decreases in intracellular calcium (Ca 2+ ) concentration, thus reducing the Ca 2+ -dependent potassium (K + ) current. In this way, the GABA-mediated hyperpolarization replaces Ca 2+ -dependent K + current; however, this inhibition is pulsatile, which allows the DA neuron to fire during the rhythmic pauses in inhibition. Our results emphasize the importance of inhibition in the VTA, which has been discussed in many studies, and suggest a novel mechanism whereby computations can occur locally. Copyright © 2016 the American Physiological Society.

Contribution of synchronized GABAergic neurons to dopaminergic neuron firing and bursting

PubMed Central

Myroshnychenko, Maxym; Zakharov, Denis; di Volo, Matteo; Gutkin, Boris; Lapish, Christopher C.; Kuznetsov, Alexey

2016-01-01

In the ventral tegmental area (VTA), interactions between dopamine (DA) and γ-aminobutyric acid (GABA) neurons are critical for regulating DA neuron activity and thus DA efflux. To provide a mechanistic explanation of how GABA neurons influence DA neuron firing, we developed a circuit model of the VTA. The model is based on feed-forward inhibition and recreates canonical features of the VTA neurons. Simulations revealed that γ-aminobutyric acid (GABA) receptor (GABAR) stimulation can differentially influence the firing pattern of the DA neuron, depending on the level of synchronization among GABA neurons. Asynchronous activity of GABA neurons provides a constant level of inhibition to the DA neuron and, when removed, produces a classical disinhibition burst. In contrast, when GABA neurons are synchronized by common synaptic input, their influence evokes additional spikes in the DA neuron, resulting in increased measures of firing and bursting. Distinct from previous mechanisms, the increases were not based on lowered firing rate of the GABA neurons or weaker hyperpolarization by the GABAR synaptic current. This phenomenon was induced by GABA-mediated hyperpolarization of the DA neuron that leads to decreases in intracellular calcium (Ca2+) concentration, thus reducing the Ca2+-dependent potassium (K+) current. In this way, the GABA-mediated hyperpolarization replaces Ca2+-dependent K+ current; however, this inhibition is pulsatile, which allows the DA neuron to fire during the rhythmic pauses in inhibition. Our results emphasize the importance of inhibition in the VTA, which has been discussed in many studies, and suggest a novel mechanism whereby computations can occur locally. PMID:27440240

Selective Ablation of GIRK Channels in Dopamine Neurons Alters Behavioral Effects of Cocaine in Mice.

PubMed

McCall, Nora M; Kotecki, Lydia; Dominguez-Lopez, Sergio; Marron Fernandez de Velasco, Ezequiel; Carlblom, Nicholas; Sharpe, Amanda L; Beckstead, Michael J; Wickman, Kevin

2017-02-01

The increase in dopamine (DA) neurotransmission stimulated by in vivo cocaine exposure is tempered by G protein-dependent inhibitory feedback mechanisms in DA neurons of the ventral tegmental area (VTA). G protein-gated inwardly rectifying K + (GIRK/Kir3) channels mediate the direct inhibitory effect of GABA B receptor (GABA B R) and D 2 DA receptor (D 2 R) activation in VTA DA neurons. Here we examined the effect of the DA neuron-specific loss of GIRK channels on D 2 R-dependent regulation of VTA DA neuron excitability and on cocaine-induced, reward-related behaviors. Selective ablation of Girk2 in DA neurons did not alter the baseline excitability of VTA DA neurons but significantly reduced the magnitude of D 2 R-dependent inhibitory somatodendritic currents and blunted the impact of D 2 R activation on spontaneous activity and neuronal excitability. Mice lacking GIRK channels in DA neurons exhibited increased locomotor activation in response to acute cocaine administration and an altered locomotor sensitization profile, as well as increased responding for and intake of cocaine in an intravenous self-administration test. These mice, however, showed unaltered cocaine-induced conditioned place preference. Collectively, our data suggest that feedback inhibition to VTA DA neurons, mediated by GIRK channel activation, tempers the locomotor stimulatory effect of cocaine while also modulating the reinforcing effect of cocaine in an operant-based self-administration task.

A novel quantum dot-laccase hybrid nanobiosensor for low level determination of dopamine.

PubMed

Shamsipur, Mojtaba; Shanehasz, Maryam; Khajeh, Khosro; Mollania, Nasrin; Kazemi, Sayyed Habib

2012-12-07

This work reports a novel nanobiosensor based on a thioglycolic acid (TGA)-capped CdTe quantum dot-laccase (Lac) enzyme system for sensitive detection of dopamine (DA). The enzyme used catalyzes the oxidation of DA to dopamine-o-quinone (DOQ), which can selectively quench the strong luminescence of CdTe nanocrystals at neutral pH. The relationship between luminescence intensity of CdTe nanocrystals and DA concentration is nicely described by the Stern-Volmer equation. At an optimum pH of 7.4, the proposed sensor gives a linear calibration over a DA concentration range of 0.3 to 100 μM, with a limit of detection of 0.16 μM and a response time of 2 min. The relative standard deviation for seven replicate determinations of 6.0 μM of DA was found to be 3.7%. The sensor was successfully applied to the determination of DA in a blood plasma sample and in a DA injection formulation.

Estimating Anthropometric Marker Locations from 3-D LADAR Point Clouds

DTIC Science & Technology

2011-06-01

http://perception.inrialpes. fr/Publications/2008/CMKBH08. [17] Da Vinci , L. The Notebooks of Leonardo Da Vinci Complete. Public Domain, 2004. [18] Duda...the problem is based on historical research into the proper proportioning of the human body. A famous example of this research is Leonardo da Vinci’s

A novel and simple strategy for simultaneous determination of dopamine, uric acid and ascorbic acid based on the stacked graphene platelet nanofibers/ionic liquids/chitosan modified electrode.

PubMed

Niu, Xiuli; Yang, Wu; Guo, Hao; Ren, Jie; Yang, Fusheng; Gao, Jinzhang

2012-09-15

A promising electrochemical sensor for simultaneous determination of dopamine (DA), uric acid (UA) and ascorbic acid (AA) was fabricated based on the stacked graphene platelet nanofibers (SGNF)/ionic liquid (IL)/chitosan (CS) modified electrode. The SGNF/IL/CS modified electrode possessed excellent electrocatalytic activity towards the oxidation of DA, UA and AA with obvious reduction of over-potential and increased peak current, and the separations of oxidation peak potentials of DA-UA, DA-AA, and UA-AA were of 151, 213 and 364 mV, respectively. Under the optimum conditions, the linear range for the detection of DA, UA and AA were 0.05-240, 0.12-260, and 30-350 μM with the lowest detection limits of 0.05, 0.10 and 14.8 μM for DA, UA and AA, respectively. In addition, the electrochemical sensor showed high sensitivity, excellent selectivity, reproducibility and long-term stability. Copyright © 2012 Elsevier B.V. All rights reserved.

Transoral robotic surgery for the base of tongue squamous cell carcinoma: a preliminary comparison between da Vinci Xi and Si.

PubMed

Alessandrini, Marco; Pavone, Isabella; Micarelli, Alessandro; Caporale, Claudio

2017-09-13

Considering the emerging advantages related to da Vinci Xi robotic platform, the aim of this study is to compare for the first time the operative outcomes of this tool to the previous da Vinci Si during transoral robotic surgery (TORS), both performed for squamous cell carcinomas (SCC) of the base of tongue (BOT). Intra- and peri-operative outcomes of eight patients with early stage (T1-T2) of the BOT carcinoma and undergoing TORS by means of the da Vinci Xi robotic platform (Xi-TORS) are compared with the da Vinci Si group ones (Si-TORS). With respect to Si-TORS group, Xi-TORS group demonstrated a significantly shorter overall operative time, console time, and intraoperative blood loss, as well as peri-operative pain intensity and length of mean hospital stays and nasogastric tube positioning. Considering recent advantages offered by surgical robotic techniques, the da Vinci Xi Surgical System preliminary outcomes could suggest its possible future routine implementation in BOT squamous cell carcinoma procedures.

The causal nature of the association between neighborhood deprivation and drug abuse: a prospective national Swedish co-relative control study

PubMed Central

Kendler, K. S.; Ohlsson, H.; Sundquist, K.; Sundquist, J.

2014-01-01

Background Risk for drug abuse (DA) is strongly associated with neighborhood social deprivation (SD). However, the causal nature of this relationship is unclear. Method Three Swedish population-based cohorts were followed up over 5 years for incident registration of DA in medical, legal or pharmacy records. In each cohort, we examined the SD–DA association, controlling carefully for individual socio-economic status (SES) with multiple measures, in the entire sample and among pairs of first cousins, paternal and maternal half-siblings, full siblings and monozygotic (MZ) twins discordant for SD exposure. The number of informative relative pairs ranged from 6366 to 166208. Results In all cohorts, SD was prospectively related to risk for incident DA. In relative pairs discordant for SD exposure, the SD–DA association was similar to that seen in the entire population in cousins, half-siblings, full siblings and MZ twins. Eliminating subjects who were residentially unstable or had DA in the first two follow-up years did not alter this pattern. When divided by age, in the youngest groups, the SD–DA association was weaker in siblings than in the entire population. Conclusions Across three cohorts, controlling for individual SES and confounding familial factors, SD prospectively predicted risk for incident DA registration. These results support the hypothesis that the SD–DA association is in part causal and unlikely to result entirely from personal attributes, which both increase risk for DA and cause selection into high SD environments. At least part of the SD–DA association arises because exposure to SD causes an increased risk of DA. PMID:25055172

Development of a decision aid for the treatment of benign prostatic hyperplasia: A four stage method using a Delphi consensus study.

PubMed

Lamers, Romy E D; Cuypers, Maarten; Garvelink, Mirjam M; de Vries, Marieke; Bosch, J L H Ruud; Kil, Paul J M

2016-07-01

To develop a web-based decision aid (DA) for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH). From February-September 2014 we performed a four-stage development method: 1: Two-round Delphi consensus method among urologists, 2: Identifying patients' needs and expectations, 3: Development of DA content and structure, 4: Usability testing with LUTS/BPH patients. 1 (N=15): Dutch urologists reached consensus on 61% of the statements concerning users' criteria, decision options, structure, and medical content. 2 (N=24): Consensus was reached in 69% on statements concerning the need for improvement of information provision, the need for DA development and that the DA should clarify patients' preferences. 3: DA development based on results from stage 1 and stage 2. 4 (N=10): Pros of the DA were clear information provision, systematic design and easy to read and re-read. A LUTS/BPH DA containing VCEs(**) was developed in cooperation with urologists and patients following a structured 4 stage method and was stated to be well accepted. This method can be adopted for the development of DAs to support other medical decision issues. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Da-KGM based GO-reinforced FMBO-loaded aerogels for efficient arsenic removal in aqueous solution.

PubMed

Ye, Shuxin; Jin, Weiping; Huang, Qing; Hu, Ying; Li, Yan; Li, Jing; Li, Bin

2017-01-01

Composites based on deacetylated konjac glucomannan (Da-KGM) and graphene oxide (GO) aerogels with iron and manganese oxides (FMBO) for effective removal of arsenic from contaminated water. Da-KGM, which was used as supporting composite matrix here, were firstly treated with GO and loaded FMBO. The obtained Da-KGM/GO/FMBO composite aerogels were characterized by compression test, thermo gravimetric analysis (TGA), X-ray diffraction (XRD), fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The characteristic results showed that addition of GO exhibited enhanced mechanical properties towards Da-KGM aerogels. What's more, results of FTIR indicated the strong intermolecular hydrogen bond interaction between KGM and GO. Batch adsorption tests were used to evaluate arsenic removal capacity. Da-KGM/GO loaded FMBO composite aerogels exhibited high adsorption ability for arsenite [As(III)] and arsenate [As(V)]. The adsorption results showed that the arsenic for both arsenite [As(III)] and arsenate [As(V)] removal process followed a pseudo-second-order rate equation and Langmuir monolayer adsorption. The maximum As(III) and As(V) uptake capacity of Da-KGM/GO(10%)/FMBO composite aerogels reached 30.21mgg -1 and 12.08mgg -1 respectively according to Langmuir isotherm at pH 7 and 323K. Copyright © 2016 Elsevier B.V. All rights reserved.

The genome sequence of Agrotis segetum granulovirus, isolate AgseGV-DA, reveals a new Betabaculovirus species of a slow killing granulovirus.

PubMed

Gueli Alletti, Gianpiero; Eigenbrod, Marina; Carstens, Eric B; Kleespies, Regina G; Jehle, Johannes A

2017-06-01

The European isolate Agrotis segetum granulovirus DA (AgseGV-DA) is a slow killing, type I granulovirus due to low dose-mortality responses within seven days post infection and a tissue tropism of infection restricted solely to the fat body of infected Agrotis segetum host larvae. The genome of AgseGV-DA was completely sequenced and compared to the whole genome sequences of the Chinese isolates AgseGV-XJ and AgseGV-L1. All three isolates share highly conserved genomes. The AgseGV-DA genome is 131,557bp in length and encodes for 149 putative open reading frames, including 37 baculovirus core genes and the per os infectivity factor ac110. Comprehensive investigations of repeat regions identified one putative non-hr like origin of replication in AgseGV-DA. Phylogenetic analysis based on concatenated amino acid alignments of 37 baculovirus core genes as well as pairwise distances based on the nucleotide alignments of partial granulin, lef-8 and lef-9 sequences with deposited betabaculoviruses confirmed AgseGV-DA, AgseGV-XJ and AgseGV-L1 as representative isolates of the same Betabaculovirus species. AgseGV encodes for a distinct putative enhancin, distantly related to enhancins from other granuloviruses. Copyright © 2017. Published by Elsevier Inc.

A pseudoproxy assessment of data assimilation for reconstructing the atmosphere-ocean dynamics of hydroclimate extremes

NASA Astrophysics Data System (ADS)

Steiger, Nathan J.; Smerdon, Jason E.

2017-10-01

Because of the relatively brief observational record, the climate dynamics that drive multiyear to centennial hydroclimate variability are not adequately characterized and understood. Paleoclimate reconstructions based on data assimilation (DA) optimally fuse paleoclimate proxies with the dynamical constraints of climate models, thus providing a coherent dynamical picture of the past. DA is therefore an important new tool for elucidating the mechanisms of hydroclimate variability over the last several millennia. But DA has so far remained untested for global hydroclimate reconstructions. Here we explore whether or not DA can be used to skillfully reconstruct global hydroclimate variability along with the driving climate dynamics. Through a set of idealized pseudoproxy experiments, we find that an established DA reconstruction approach can in principle be used to reconstruct hydroclimate at both annual and seasonal timescales. We find that the skill of such reconstructions is generally highest near the proxy sites. This set of reconstruction experiments is specifically designed to estimate a realistic upper bound for the skill of this DA approach. Importantly, this experimental framework allows us to see where and for what variables the reconstruction approach may never achieve high skill. In particular for tree rings, we find that hydroclimate reconstructions depend critically on moisture-sensitive trees, while temperature reconstructions depend critically on temperature-sensitive trees. Real-world DA-based reconstructions will therefore likely require a spatial mixture of temperature- and moisture-sensitive trees to reconstruct both temperature and hydroclimate variables. Additionally, we illustrate how DA can be used to elucidate the dynamical mechanisms of drought with two examples: tropical drivers of multiyear droughts in the North American Southwest and in equatorial East Africa. This work thus provides a foundation for future DA-based hydroclimate reconstructions using real-proxy networks while also highlighting the utility of this important tool for hydroclimate research.

Boletim and Arquivos: scientific communication until the creation of the Revista de Saúde Pública.

PubMed

Marques, Maria Cristina da Costa; Dolci, Mariana de Carvalho

2016-10-24

Based on historical references of scientific communication, we analyzed the issues of the Boletim do Instituto de Higiene de São Paulo and of the Arquivos da Faculdade de Higiene e Saúde Pública da Universidade de São Paulo. Published respectively from 1919 to 1946 and from 1947 to 1966, they totaled 120 issues. In their 48 years of publication, their goal was to disseminate the scientific production of the institution and to legitimize the theoretical debate of the field, in addition to supporting the public health intervention models, written by leading researchers of the institution and by contributors and managers in the field of public health. Both the Boletim and the Arquivos were recognized as scientific communication of national reference, and have laid the foundations for the creation of the Revista de Saúde Pública, in 1967. RESUMO Com base em referenciais históricos da comunicação científica, foram analisadas as edições do Boletim do Instituto de Higiene de São Paulo e dos Arquivos da Faculdade de Higiene e Saúde Pública da Universidade de São Paulo. Publicadas respectivamente de 1919 a 1946 e de 1947 a 1966, totalizam 120 edições. Em seus 48 anos de publicação, o objetivo era disseminar a produção científica da instituição e legitimar o debate teórico do campo, além de apoiar os modelos de intervenção de saúde pública, escrita por importantes pesquisadores da instituição e colaboradores e gestores do campo da saúde pública. Tanto o Boletim como os Arquivos foram reconhecidos como comunicação científica de referência nacional e lançaram as bases para a criação da Revista de Saúde Pública, em 1967.

Nano-LC FTICR tandem mass spectrometry for top-down proteomics: routine baseline unit mass resolution of whole cell lysate proteins up to 72 kDa.

PubMed

Tipton, Jeremiah D; Tran, John C; Catherman, Adam D; Ahlf, Dorothy R; Durbin, Kenneth R; Lee, Ji Eun; Kellie, John F; Kelleher, Neil L; Hendrickson, Christopher L; Marshall, Alan G

2012-03-06

Current high-throughput top-down proteomic platforms provide routine identification of proteins less than 25 kDa with 4-D separations. This short communication reports the application of technological developments over the past few years that improve protein identification and characterization for masses greater than 25 kDa. Advances in separation science have allowed increased numbers of proteins to be identified, especially by nanoliquid chromatography (nLC) prior to mass spectrometry (MS) analysis. Further, a goal of high-throughput top-down proteomics is to extend the mass range for routine nLC MS analysis up to 80 kDa because gene sequence analysis predicts that ~70% of the human proteome is transcribed to be less than 80 kDa. Normally, large proteins greater than 50 kDa are identified and characterized by top-down proteomics through fraction collection and direct infusion at relatively low throughput. Further, other MS-based techniques provide top-down protein characterization, however at low resolution for intact mass measurement. Here, we present analysis of standard (up to 78 kDa) and whole cell lysate proteins by Fourier transform ion cyclotron resonance mass spectrometry (nLC electrospray ionization (ESI) FTICR MS). The separation platform reduced the complexity of the protein matrix so that, at 14.5 T, proteins from whole cell lysate up to 72 kDa are baseline mass resolved on a nano-LC chromatographic time scale. Further, the results document routine identification of proteins at improved throughput based on accurate mass measurement (less than 10 ppm mass error) of precursor and fragment ions for proteins up to 50 kDa.

Differential Dopamine Release Dynamics in the Nucleus Accumbens Core and Shell Reveal Complementary Signals for Error Prediction and Incentive Motivation

PubMed Central

Cacciapaglia, Fabio; Wightman, R. Mark; Carelli, Regina M.

2015-01-01

Mesolimbic dopamine (DA) is phasically released during appetitive behaviors, though there is substantive disagreement about the specific purpose of these DA signals. For example, prediction error (PE) models suggest a role of learning, while incentive salience (IS) models argue that the DA signal imbues stimuli with value and thereby stimulates motivated behavior. However, within the nucleus accumbens (NAc) patterns of DA release can strikingly differ between subregions, and as such, it is possible that these patterns differentially contribute to aspects of PE and IS. To assess this, we measured DA release in subregions of the NAc during a behavioral task that spatiotemporally separated sequential goal-directed stimuli. Electrochemical methods were used to measure subsecond NAc dopamine release in the core and shell during a well learned instrumental chain schedule in which rats were trained to press one lever (seeking; SL) to gain access to a second lever (taking; TL) linked with food delivery, and again during extinction. In the core, phasic DA release was greatest following initial SL presentation, but minimal for the subsequent TL and reward events. In contrast, phasic shell DA showed robust release at all task events. Signaling decreased between the beginning and end of sessions in the shell, but not core. During extinction, peak DA release in the core showed a graded decrease for the SL and pauses in release during omitted expected rewards, whereas shell DA release decreased predominantly during the TL. These release dynamics suggest parallel DA signals capable of supporting distinct theories of appetitive behavior. SIGNIFICANCE STATEMENT Dopamine signaling in the brain is important for a variety of cognitive functions, such as learning and motivation. Typically, it is assumed that a single dopamine signal is sufficient to support these cognitive functions, though competing theories disagree on how dopamine contributes to reward-based behaviors. Here, we have found that real-time dopamine release within the nucleus accumbens (a primary target of midbrain dopamine neurons) strikingly varies between core and shell subregions. In the core, dopamine dynamics are consistent with learning-based theories (such as reward prediction error) whereas in the shell, dopamine is consistent with motivation-based theories (e.g., incentive salience). These findings demonstrate that dopamine plays multiple and complementary roles based on discrete circuits that help animals optimize rewarding behaviors. PMID:26290234

Reduced dopamine receptors and transporters but not synthesis capacity in normal aging adults: a meta-analysis.

PubMed

Karrer, Teresa M; Josef, Anika K; Mata, Rui; Morris, Evan D; Samanez-Larkin, Gregory R

2017-09-01

Many theories of cognitive aging are based on evidence that dopamine (DA) declines with age. Here, we performed a systematic meta-analysis of cross-sectional positron emission tomography and single-photon emission-computed tomography studies on the average effects of age on distinct DA targets (receptors, transporters, or relevant enzymes) in healthy adults (N = 95 studies including 2611 participants). Results revealed significant moderate to large, negative effects of age on DA transporters and receptors. Age had a significantly larger effect on D1- than D2-like receptors. In contrast, there was no significant effect of age on DA synthesis capacity. The average age reductions across the DA system were 3.7%-14.0% per decade. A meta-regression found only DA target as a significant moderator of the age effect. This study precisely quantifies prior claims of reduced DA functionality with age. It also identifies presynaptic mechanisms (spared synthesis capacity and reduced DA transporters) that may partially account for previously unexplained phenomena whereby older adults appear to use dopaminergic resources effectively. Recommendations for future studies including minimum required samples sizes are provided. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice.

PubMed

Moon, Eunjung; Lee, Sung Ok; Kang, Tong Ho; Kim, Hye Ju; Choi, Sang Zin; Son, Mi-Won; Kim, Sun Yeou

2014-09-01

The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study.

Autoradiographic evidence for methamphetamine-induced striatal dopaminergic loss in mouse brain: attenuation in CuZn-superoxide dismutase transgenic mice.

PubMed

Hirata, H; Ladenheim, B; Carlson, E; Epstein, C; Cadet, J L

1996-04-01

Methamphetamine (METH) has long-lasting neurotoxic effects on the nigrostriatal dopamine (DA) system of rodents. METH-induced neurotoxicity is thought to involve release of DA in presynaptic DA terminals, which is associated with increased formation of oxygen-based free radicals. We have recently shown that METH-induced striatal DA depletion is attenuated in transgenic (Tg) mice that express the human CuZn-superoxide dismutase (SOD) enzyme. That study did not specifically address the issue of loss of DA terminals. In the present study, we have used receptor autoradiographic studies of [(125)I]RTI-121-labeled DA uptake sites to evaluate the effects of several doses of METH on striatal DA terminals of Non-Tg as well as of heterozygous and homozygous SOD-Tg mice. In Non-Tg mice, METH caused decreases in striatal DA uptake sites in a dose-dependent fashion. The loss of DA terminals was more prominent in the lateral region than in the medial subdivisions of the striatum. In SOD-Tg mice, the loss of DA terminals caused by METH was attenuated in a gene dosage-dependent fashion, with the homozygous mice showing the greatest protection. Female mice were somewhat more resistant than male mice against these deleterious effects of METH. These results provide further evidence for a role of superoxide radicals in the long-term effects of METH. They also suggest the notion of a gender-specific handling of oxidative stress.

Impact of a web-based prostate cancer treatment decision aid on patient-reported decision process parameters: results from the Prostate Cancer Patient Centered Care trial.

PubMed

Cuypers, Maarten; Lamers, Romy E D; Kil, Paul J M; van de Poll-Franse, Lonneke V; de Vries, Marieke

2018-05-12

To compare patients' evaluation of the treatment decision-making process in localized prostate cancer between counseling that included an online decision aid (DA) and standard counseling. Eighteen Dutch hospitals were randomized to DA counseling (n = 235) or the control group with standard counseling (n = 101) in a pragmatic, cluster randomized controlled trial. The DA was provided to patients at, or soon after diagnosis. Decisional conflict, involvement, knowledge, and satisfaction with information were assessed with a questionnaire after treatment decision-making. Anxiety and depression served as covariates. The levels of decision involvement and conflict were comparable between patients in both groups. Patients with a DA felt more knowledgeable but scored equally well on a knowledge test as patients without a DA. Small significant negative effects were found on satisfaction with information and preparation for decision-making. A preference for print over online and depression and anxiety symptoms was negatively associated with satisfaction and conflict scores in the DA group. The DA aimed to support shared decision-making, while outcomes for a majority of DA users were comparable to patients who received standard counseling. Patients, who are less comfortable with the online DA format or experience anxiety or depression symptoms, could require more guidance toward shared decision-making. To evaluate long-term DA effects, follow-up evaluation on treatment satisfaction and decisional regret will be done.

A sensing approach for dopamine determination by boronic acid-functionalized molecularly imprinted graphene quantum dots composite

NASA Astrophysics Data System (ADS)

Zhou, Xi; Gao, Xuexia; Song, Fengyan; Wang, Chunpeng; Chu, Fuxiang; Wu, Shishan

2017-11-01

A novel fluorescence sensor was developed for dopamine (DA) determination based on molecularly imprinted graphene quantum dots and poly(indolylboronic acid) composite (MIPs@ PIn-BAc/GQDs). When the DA is added to the system, it leads to an aggregation and fluorescence quenching of the MIPs@ PIn-BAc/GQDs because of the covalent binding between the catechol group of DA and boronic acid. Such fluorescence behaviors are used for well testing DA in a range from 5 × 10-9 to 1.2 × 10-6 M with the detection limit of 2.5 × 10-9 M. Furthermore, the prepared sensors could well against the interferences from various biomolecules and be successfully used for the assay of DA in human biological samples, exhibiting excellent specificity. It is believed that the prepared MIPs@ PIn-BAc/GQDs hold great promise as a practical platform that can monitor DA level change.

Dopamine prediction errors in reward learning and addiction: from theory to neural circuitry

PubMed Central

Keiflin, Ronald; Janak, Patricia H.

2015-01-01

Summary Midbrain dopamine (DA) neurons are proposed to signal reward prediction error (RPE), a fundamental parameter in associative learning models. This RPE hypothesis provides a compelling theoretical framework for understanding DA function in reward learning and addiction. New studies support a causal role for DA-mediated RPE activity in promoting learning about natural reward; however, this question has not been explicitly tested in the context of drug addiction. In this review, we integrate theoretical models with experimental findings on the activity of DA systems, and on the causal role of specific neuronal projections and cell types, to provide a circuit-based framework for probing DA-RPE function in addiction. By examining error-encoding DA neurons in the neural network in which they are embedded, hypotheses regarding circuit-level adaptations that possibly contribute to pathological error-signaling and addiction can be formulated and tested. PMID:26494275

The causes of parent–offspring transmission of drug abuse: a Swedish population-based study

PubMed Central

Kendler, K. S.; Ohlsson, H.; Sundquist, K.; Sundquist, J.

2014-01-01

Background While drug abuse (DA) is strongly familial, we still have limited knowledge about the causes of its cross-generational transmission. Method We examined DA ascertained from national registers in offspring of three family types from the Swedish population [intact (n=2111074), ‘not-lived-with’ (n = 165315, where biological parents never lived with their offspring) and ‘step’ (n = 124800 offspring)], which reflected, respectively, the effects of genes+rearing, genes only and rearing only. We replicated these results in three high-risk co-relative designs. Results Combined across mothers and fathers, the hazard ratio (HR) for DA in offspring given DA in parents was 3.52 in intact, 2.73 in ‘not-lived-with’ and 1.79 in stepfamilies. In 968 biological full or half-sibling pairs one of whom was reared by and the other never lived with their parent with DA, the HR for DA was greater in the reared than ‘not-lived-with’ child (HR 1.57). In 64 offspring pairs of a parent with DA, the HR for DA was greater in a reared biological v. step-parented non-biological child (HR 3.33). In 321 pairs of offspring of a parent with DA one of whom was a not-lived-with biological child and the second a step-parented non-biological child, the HR for DA was greater in the biological v. stepchild (HR 1.80). Conclusions Both genetic and environmental factors contribute substantially to parent–offspring resemblance for DA. The general population contains informative family constellations that can complement more traditional adoption designs in clarifying the sources of parent–offspring resemblance. PMID:25066684

The causes of parent-offspring transmission of drug abuse: a Swedish population-based study.

PubMed

Kendler, K S; Ohlsson, H; Sundquist, K; Sundquist, J

2015-01-01

While drug abuse (DA) is strongly familial, we still have limited knowledge about the causes of its cross-generational transmission. We examined DA ascertained from national registers in offspring of three family types from the Swedish population [intact (n = 2,111,074), 'not-lived-with' (n = 165,315, where biological parents never lived with their offspring) and 'step' (n = 124,800 offspring)], which reflected, respectively, the effects of genes + rearing, genes only and rearing only. We replicated these results in three high-risk co-relative designs. Combined across mothers and fathers, the hazard ratio (HR) for DA in offspring given DA in parents was 3.52 in intact, 2.73 in 'not-lived-with' and 1.79 in stepfamilies. In 968 biological full or half-sibling pairs one of whom was reared by and the other never lived with their parent with DA, the HR for DA was greater in the reared than 'not-lived-with' child (HR 1.57). In 64 offspring pairs of a parent with DA, the HR for DA was greater in a reared biological v. step-parented non-biological child (HR 3.33). In 321 pairs of offspring of a parent with DA one of whom was a not-lived-with biological child and the second a step-parented non-biological child, the HR for DA was greater in the biological v. stepchild (HR 1.80). Both genetic and environmental factors contribute substantially to parent-offspring resemblance for DA. The general population contains informative family constellations that can complement more traditional adoption designs in clarifying the sources of parent-offspring resemblance.

Vectra DA for the objective measurement of disease activity in patients with rheumatoid arthritis.

PubMed

Segurado, O G; Sasso, E H

2014-01-01

Quantitative and regular assessment of disease activity in rheumatoid arthritis (RA) is required to achieve treatment targets such as remission and to optimize clinical outcomes. To assess inflammation accurately, predict joint damage and monitor treatment response, a measure of disease activity in RA should reflect the pathological processes resulting in irreversible joint damage and functional disability. The Vectra DA blood test is an objective measure of disease activity for patients with RA. Vectra DA provides an accurate, reproducible score on a scale of 1 to 100 based on the concentrations of 12 biomarkers that reflect the pathophysiologic diversity of RA. The analytical validity, clinical validity, and clinical utility of Vectra DA have been evaluated for patients with RA in registries and prospective and retrospective clinical studies. As a biomarker-based instrument for assessing disease activity in RA, the Vectra DA test can help monitor therapeutic response to methotrexate and biologic agents and assess clinically challenging situations, such as when clinical measures are confounded by non-inflammatory pain from fibromyalgia. Vectra DA scores correlate with imaging of joint inflammation and are predictive for radiographic progression, with high Vectra DA scores being associated with more frequent and severe progression and low scores being predictive for non-progression. In summary, the Vectra DA score is an objective measure of RA disease activity that quantifies inflammatory status. By predicting risk for joint damage more effectively than conventional clinical and laboratory measures, it has the potential to complement these measures and optimise clinical decision making.

Synthesis of concentric circular antenna arrays using dragonfly algorithm

NASA Astrophysics Data System (ADS)

Babayigit, B.

2018-05-01

Due to the strong non-linear relationship between the array factor and the array elements, concentric circular antenna array (CCAA) synthesis problem is challenging. Nature-inspired optimisation techniques have been playing an important role in solving array synthesis problems. Dragonfly algorithm (DA) is a novel nature-inspired optimisation technique which is based on the static and dynamic swarming behaviours of dragonflies in nature. This paper presents the design of CCAAs to get low sidelobes using DA. The effectiveness of the proposed DA is investigated in two different (with and without centre element) cases of two three-ring (having 4-, 6-, 8-element or 8-, 10-, 12-element) CCAA design. The radiation pattern of each design cases is obtained by finding optimal excitation weights of the array elements using DA. Simulation results show that the proposed algorithm outperforms the other state-of-the-art techniques (symbiotic organisms search, biogeography-based optimisation, sequential quadratic programming, opposition-based gravitational search algorithm, cat swarm optimisation, firefly algorithm, evolutionary programming) for all design cases. DA can be a promising technique for electromagnetic problems.

Developing EFL Learners' Speaking Skills through Dynamic Assessment: A Case of A Beginner and an Advanced Learner

ERIC Educational Resources Information Center

Ebadi, Saman; Asakereh, Ahmad

2017-01-01

Dynamic assessment (DA), having its theoretical base in Vygotskyan Sociocultural theory of mind, is a newly developed classroom assessment through which learners are helped to perform beyond their current ability. Drawing upon the theoretical aspect of DA, the present study explored the impact of DA on the development of speaking skills. To this…

Rapid and Highly Sensitive Detection of Dopamine Using Conjugated Oxaborole-Based Polymer and Glycopolymer Systems.

PubMed

Jiang, Keren; Wang, Yinan; Thakur, Garima; Kotsuchibashi, Yohei; Naicker, Selvaraj; Narain, Ravin; Thundat, Thomas

2017-05-10

A conjugated polymer interface consisting of an oxaborole containing polymer and a glycopolymer was used for achieving very high selectivity in dopamine (DA) detection. The optimum binding affinity between the polymers promotes the selectivity to DA through a displacement mechanism while remaining unaffected by other structurally related analogs and saccharide derivatives. Real-time detection of DA with very high selectivity and sensitivity has been demonstrated by immobilizing the polymer conjugates on surface plasmon resonance (SPR) and microcantilever (MCL) sensor platforms. Using the conjugated polymer sensing layer, the SPR biosensor was capable of detecting DA in the concentration range of 1 × 10 -9 to 1 × 10 -4 mol L -1 , whereas the MCL sensor showed a limit of detection (LOD) of 5 × 10 -11 mol L -1 . We find that the sensing mechanism is based on DA-induced reversible swelling of the conjugated polymer layer and this allows regeneration and reuse of the sensor multiple times. Also, we conclude that SPR is a suitable sensor platform for DA in-line detection at clinical level considering the detection time and stability, whereas MCL can achieve a much lower LOD.

Defining donor and acceptor strength in conjugated copolymers

NASA Astrophysics Data System (ADS)

Hedström, Svante; Wang, Ergang; Persson, Petter

2017-03-01

The progress in efficiency of organic photovoltaic devices is largely driven by the development of new donor-acceptor (D-A) copolymers. The number of possible D-A combinations escalates rapidly with the ever-increasing number of donor and acceptor units, and the design process often involves a trial-and-error approach. We here present a computationally efficient methodology for the prediction of optical and electronic properties of D-A copolymers based on density functional theory calculations of donor- and acceptor-only homopolymers. Ten donors and eight acceptors are studied, as well as all of their 80 D-A copolymer combinations, showing absorption energies of 1.3-2.3 eV, and absorption strengths varying by up to a factor of 2.5. Focus lies on exhibited trends in frontier orbital energies, optical band gaps, and absorption intensities, as well as their relation to the molecular structure. Based on the results, we define the concept of donor and acceptor strength, and calculate this quantity for all investigated units. The light-harvesting capabilities of the 80 D-A copolymers were also assessed. This gives a valuable theoretical guideline to the design of D-A copolymers with the potential to reduce the synthesis efforts in the development of new polymers.

PCA as a practical indicator of OPLS-DA model reliability.

PubMed

Worley, Bradley; Powers, Robert

Principal Component Analysis (PCA) and Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) are powerful statistical modeling tools that provide insights into separations between experimental groups based on high-dimensional spectral measurements from NMR, MS or other analytical instrumentation. However, when used without validation, these tools may lead investigators to statistically unreliable conclusions. This danger is especially real for Partial Least Squares (PLS) and OPLS, which aggressively force separations between experimental groups. As a result, OPLS-DA is often used as an alternative method when PCA fails to expose group separation, but this practice is highly dangerous. Without rigorous validation, OPLS-DA can easily yield statistically unreliable group separation. A Monte Carlo analysis of PCA group separations and OPLS-DA cross-validation metrics was performed on NMR datasets with statistically significant separations in scores-space. A linearly increasing amount of Gaussian noise was added to each data matrix followed by the construction and validation of PCA and OPLS-DA models. With increasing added noise, the PCA scores-space distance between groups rapidly decreased and the OPLS-DA cross-validation statistics simultaneously deteriorated. A decrease in correlation between the estimated loadings (added noise) and the true (original) loadings was also observed. While the validity of the OPLS-DA model diminished with increasing added noise, the group separation in scores-space remained basically unaffected. Supported by the results of Monte Carlo analyses of PCA group separations and OPLS-DA cross-validation metrics, we provide practical guidelines and cross-validatory recommendations for reliable inference from PCA and OPLS-DA models.

The Atypical MAP Kinase SWIP-13/ERK8 Regulates Dopamine Transporters through a Rho-Dependent Mechanism

PubMed Central

Bermingham, Daniel P.; Snider, Sam L.; Miller, David M.

2017-01-01

The neurotransmitter dopamine (DA) regulates multiple behaviors across phylogeny, with disrupted DA signaling in humans associated with addiction, attention-deficit/ hyperactivity disorder, schizophrenia, and Parkinson's disease. The DA transporter (DAT) imposes spatial and temporal limits on DA action, and provides for presynaptic DA recycling to replenish neurotransmitter pools. Molecular mechanisms that regulate DAT expression, trafficking, and function, particularly in vivo, remain poorly understood, though recent studies have implicated rho-linked pathways in psychostimulant action. To identify genes that dictate the ability of DAT to sustain normal levels of DA clearance, we pursued a forward genetic screen in Caenorhabditis elegans based on the phenotype swimming-induced paralysis (Swip), a paralytic behavior observed in hermaphrodite worms with loss-of-function dat-1 mutations. Here, we report the identity of swip-13, which encodes a highly conserved ortholog of the human atypical MAP kinase ERK8. We present evidence that SWIP-13 acts presynaptically to insure adequate levels of surface DAT expression and DA clearance. Moreover, we provide in vitro and in vivo evidence supporting a conserved pathway involving SWIP-13/ERK8 activation of Rho GTPases that dictates DAT surface expression and function. SIGNIFICANCE STATEMENT Signaling by the neurotransmitter dopamine (DA) is tightly regulated by the DA transporter (DAT), insuring efficient DA clearance after release. Molecular networks that regulate DAT are poorly understood, particularly in vivo. Using a forward genetic screen in the nematode Caenorhabditis elegans, we implicate the atypical mitogen activated protein kinase, SWIP-13, in DAT regulation. Moreover, we provide in vitro and in vivo evidence that SWIP-13, as well as its human counterpart ERK8, regulate DAT surface availability via the activation of Rho proteins. Our findings implicate a novel pathway that regulates DA synaptic availability and that may contribute to risk for disorders linked to perturbed DA signaling. Targeting this pathway may be of value in the development of therapeutics in such disorders. PMID:28842414

Human dopamine receptor nanovesicles for gate-potential modulators in high-performance field-effect transistor biosensors

NASA Astrophysics Data System (ADS)

Park, Seon Joo; Song, Hyun Seok; Kwon, Oh Seok; Chung, Ji Hyun; Lee, Seung Hwan; An, Ji Hyun; Ahn, Sae Ryun; Lee, Ji Eun; Yoon, Hyeonseok; Park, Tai Hyun; Jang, Jyongsik

2014-03-01

The development of molecular detection that allows rapid responses with high sensitivity and selectivity remains challenging. Herein, we demonstrate the strategy of novel bio-nanotechnology to successfully fabricate high-performance dopamine (DA) biosensor using DA Receptor-containing uniform-particle-shaped Nanovesicles-immobilized Carboxylated poly(3,4-ethylenedioxythiophene) (CPEDOT) NTs (DRNCNs). DA molecules are commonly associated with serious diseases, such as Parkinson's and Alzheimer's diseases. For the first time, nanovesicles containing a human DA receptor D1 (hDRD1) were successfully constructed from HEK-293 cells, stably expressing hDRD1. The nanovesicles containing hDRD1 as gate-potential modulator on the conducting polymer (CP) nanomaterial transistors provided high-performance responses to DA molecule owing to their uniform, monodispersive morphologies and outstanding discrimination ability. Specifically, the DRNCNs were integrated into a liquid-ion gated field-effect transistor (FET) system via immobilization and attachment processes, leading to high sensitivity and excellent selectivity toward DA in liquid state. Unprecedentedly, the minimum detectable level (MDL) from the field-induced DA responses was as low as 10 pM in real- time, which is 10 times more sensitive than that of previously reported CP based-DA biosensors. Moreover, the FET-type DRNCN biosensor had a rapid response time (<1 s) and showed excellent selectivity in human serum.

Innovation and communicative action: health management networks and technologies.

PubMed

Rivera, Francisco Javier Uribe; Artmann, Elizabeth

2016-11-03

This article discusses elements of a theory of innovation from the perspective of innovation networks and social construction of technology, based on Habermas' Theory of Communicative Action and authors from the Sociology of Innovation. Based on the theoretical framework of the communicative production of scientific facts, we focus on innovation management as a basic dimension that must meet some organizational and methodological requirements in order to power its results. We present and discuss instruments such as Situational Planning, Prospective Analysis, Strategic Portfolio Management, and Networks Management that can help deal with the challenge of innovation and exploration of the future. We conclude that network organizational formats centered on reflexivity of interdisciplinary groups and planning approaches that encourage innovation criteria in assessing the attractiveness of activities and that help anticipate forms of innovation through systematic prospective analysis can potentiate the process of generating innovation as a product of networks. Resumo: No artigo são discutidos elementos de uma teoria da inovação numa perspectiva de redes de inovação e de construção social da tecnologia, a partir da Teoria do Agir Comunicativo de Habermas e de autores da Sociologia da Inovação. Com base no marco teórico da produção comunicativa de fatos científicos, focamos a gestão da inovação como uma dimensão fundamental que deve contemplar alguns requisitos, tanto de natureza organizacional quanto metodológica, para potencializar seus resultados. Apresentamos e discutimos instrumentos como o Planejamento Situacional, a Análise Prospectiva, a Gestão Estratégica de Portfólios e a Gestão de Redes que podem contribuir para o desafio da inovação e exploração do futuro. Conclui-se que formas organizativas em rede, centradas na reflexividade de grupos interdisciplinares, e enfoques de planejamento que estimulem o uso de critérios de inovação na avaliação da atratividade das atividades e que ajudem a antecipar formas de inovação por meio de uma análise prospectiva sistemática podem potencializar o processo de geração da inovação como produto de redes.

An efficient optical-electrochemical dual probe for highly sensitive recognition of dopamine based on terbium complex functionalized reduced graphene oxide

NASA Astrophysics Data System (ADS)

Zhou, Zhan; Wang, Qianming

2014-04-01

A novel organic-inorganic hybrid sensor based on diethylenetriaminepentaacetic acid (DTPA) modified reduced graphene oxide (RGO-DTPA) chelated with terbium ions allows detection of dopamine (DA) through an emission enhancement effect. Its luminescence, peaking at 545 nm, has been improved by a factor of 25 in the presence of DA (detection limit = 80 nM). In addition, this covalently bonded terbium complex functionalized reduced graphene oxide (RGO-DTPA-Tb) can be successfully assembled on a glassy carbon electrode. The assay performed through differential pulse voltammetry (DPV) yielded obvious peak separation between DA and excessive amounts of the interfering ascorbic acid (AA).A novel organic-inorganic hybrid sensor based on diethylenetriaminepentaacetic acid (DTPA) modified reduced graphene oxide (RGO-DTPA) chelated with terbium ions allows detection of dopamine (DA) through an emission enhancement effect. Its luminescence, peaking at 545 nm, has been improved by a factor of 25 in the presence of DA (detection limit = 80 nM). In addition, this covalently bonded terbium complex functionalized reduced graphene oxide (RGO-DTPA-Tb) can be successfully assembled on a glassy carbon electrode. The assay performed through differential pulse voltammetry (DPV) yielded obvious peak separation between DA and excessive amounts of the interfering ascorbic acid (AA). Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr06156f

Identification of Variables Associated with Group Separation in Descriptive Discriminant Analysis: Comparison of Methods for Interpreting Structure Coefficients

ERIC Educational Resources Information Center

Finch, Holmes

2010-01-01

Discriminant Analysis (DA) is a tool commonly used for differentiating among 2 or more groups based on 2 or more predictor variables. DA works by finding 1 or more linear combinations of the predictors that yield maximal difference among the groups. One common goal of researchers using DA is to characterize the nature of group difference by…

Conformational preferences of DNA following damage by aristolochic acids: Structural and energetic insights into the different mutagenic potential of the ALI and ALII-N(6)-dA adducts.

PubMed

Kathuria, Preetleen; Sharma, Purshotam; Abendong, Minette N; Wetmore, Stacey D

2015-04-21

Aristolochic acids (AAI and AAII), produced by the Aristolochiaceae family of plants, are classified as group I (human) carcinogens by the International Agency for Research on Cancer. These acids are metabolized in cells to yield aristolactams (ALI and ALII, respectively), which further form bulky adducts with the purine nucleobases. Specifically, the adenine lesions are more persistent in cells and have been associated with chronic renal diseases and related carcinogenesis. To understand the structural basis of the nephrotoxicity induced by AAs, the ALI-N(6)-dA and ALII-N(6)-dA lesions are systematically studied using computational methods. Density functional theory calculations indicate that the aristolactam moiety intrinsically prefers a planar conformation with respect to adenine. Nucleoside and nucleotide models suggest that the anti and syn orientations about the glycosidic bond are isoenergetic for both adducts. Molecular dynamics simulations and free energy calculations reveal that the anti base-displaced intercalated conformation is the most stable conformer for both types of AL-N(6)-dA adducted DNA, which agrees with previous experimental work on the ALII-N(6)-dA adduct and thereby validates our approach. Interestingly, this conformer differs from the dominant conformations adopted by other N6-linked adenine lesions, including those derived from polycyclic aromatic hydrocarbons. Furthermore, the second most stable syn base-displaced intercalated conformation lies closer in energy to the anti base-displaced intercalated conformation for ALI-N(6)-dA compared to ALII-N(6)-dA. This indicates that a mixture of conformations may be detectable for ALI-N(6)-dA in DNA. If this enhanced conformational flexibility of double-stranded DNA persists when bound to a lesion-bypass polymerase, this provides a possible structural explanation for the previously observed greater nephrotoxic potential for the ALI versus ALII-N(6)-dA adduct. In addition, the structural characteristics of the preferred conformations of adducted DNA explain the resistance of these adducts to repair and thereby add to our current understanding of the toxicity of AAs within living cells.

Differential Dopamine Release Dynamics in the Nucleus Accumbens Core and Shell Reveal Complementary Signals for Error Prediction and Incentive Motivation.

PubMed

Saddoris, Michael P; Cacciapaglia, Fabio; Wightman, R Mark; Carelli, Regina M

2015-08-19

Mesolimbic dopamine (DA) is phasically released during appetitive behaviors, though there is substantive disagreement about the specific purpose of these DA signals. For example, prediction error (PE) models suggest a role of learning, while incentive salience (IS) models argue that the DA signal imbues stimuli with value and thereby stimulates motivated behavior. However, within the nucleus accumbens (NAc) patterns of DA release can strikingly differ between subregions, and as such, it is possible that these patterns differentially contribute to aspects of PE and IS. To assess this, we measured DA release in subregions of the NAc during a behavioral task that spatiotemporally separated sequential goal-directed stimuli. Electrochemical methods were used to measure subsecond NAc dopamine release in the core and shell during a well learned instrumental chain schedule in which rats were trained to press one lever (seeking; SL) to gain access to a second lever (taking; TL) linked with food delivery, and again during extinction. In the core, phasic DA release was greatest following initial SL presentation, but minimal for the subsequent TL and reward events. In contrast, phasic shell DA showed robust release at all task events. Signaling decreased between the beginning and end of sessions in the shell, but not core. During extinction, peak DA release in the core showed a graded decrease for the SL and pauses in release during omitted expected rewards, whereas shell DA release decreased predominantly during the TL. These release dynamics suggest parallel DA signals capable of supporting distinct theories of appetitive behavior. Dopamine signaling in the brain is important for a variety of cognitive functions, such as learning and motivation. Typically, it is assumed that a single dopamine signal is sufficient to support these cognitive functions, though competing theories disagree on how dopamine contributes to reward-based behaviors. Here, we have found that real-time dopamine release within the nucleus accumbens (a primary target of midbrain dopamine neurons) strikingly varies between core and shell subregions. In the core, dopamine dynamics are consistent with learning-based theories (such as reward prediction error) whereas in the shell, dopamine is consistent with motivation-based theories (e.g., incentive salience). These findings demonstrate that dopamine plays multiple and complementary roles based on discrete circuits that help animals optimize rewarding behaviors. Copyright © 2015 the authors 0270-6474/15/3511572-11$15.00/0.

76 FR 12627 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

... Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG Airplanes AGENCY: Federal Aviation Administration (FAA... on Diamond aeroplanes, the majority of which were DA 40. In additional, at least 18 doors have been... conditions) while the aeroplane was parked. All DA 40 and DA 42 aeroplanes have a system installed that...

Genome-Edited, TH-expressing Neuroblastoma Cells as a Disease Model for Dopamine-Related Disorders: A Proof-of-Concept Study on DJ-1-deficient Parkinsonism

PubMed Central

Prasuhn, Jannik; Mårtensson, Christoph U.; Krajka, Victor; Klein, Christine; Rakovic, Aleksandar

2018-01-01

Impairment of the dopaminergic (DA) system is a common cause of several movement disorders including Parkinson’s disease (PD), however, little is known about the underlying disease mechanisms. The recent development of stem-cell-based protocols for the generation of DA neurons partially solved this issue, however, this technology is costly and time-consuming. Commonly used cell lines, i.e., neuroblastoma (SHSY5Y) and PC12 cells are still widely used to investigate PD and significantly contributed to our understanding of mechanisms involved in development of the disease. However, they either do not express DA at all or require additional, only partially efficient differentiations in order to produce DA. Here we generated and characterized transgenic SH-SY5Y cells, ectopically expressing tyrosine hydroxylase (SHTH+), that can be used as a homogenous, DA-producing model to study alterations in DA metabolism and oxidative stress. We demonstrated that SHTH+ produce high levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) making this model suitable to investigate not only alterations in DA synthesis but also its turnover. We also provide evidence for the presence of other enzymes involved in DA synthesis and its turnover in these cells. Finally, we showed that these cells can easily be genetically modified using CRISPR/Cas9 technology in order to study genetically defined forms of movement disorders using DJ1-linked PD as a model. PMID:29379417

Descent advisor preliminary field test

NASA Technical Reports Server (NTRS)

Green, Steven M.; Vivona, Robert A.; Sanford, Beverly

1995-01-01

A field test of the Descent Advisor (DA) automation tool was conducted at the Denver Air Route Traffic Control Center in September 1994. DA is being developed to assist Center controllers in the efficient management and control of arrival traffic. DA generates advisories, based on trajectory predictions, to achieve accurate meter-fix arrival times in a fuel efficient manner while assisting the controller with the prediction and resolution of potential conflicts. The test objectives were to evaluate the accuracy of DA trajectory predictions for conventional- and flight-management-system-equipped jet transports, to identify significant sources of trajectory prediction error, and to investigate procedural and training issues (both air and ground) associated with DA operations. Various commercial aircraft (97 flights total) and a Boeing 737-100 research aircraft participated in the test. Preliminary results from the primary test set of 24 commercial flights indicate a mean DA arrival time prediction error of 2.4 sec late with a standard deviation of 13.1 sec. This paper describes the field test and presents preliminary results for the commercial flights.

Scientific and technological capabilities in health-related areas: opportunities, challenges, and interactions with the industrial sector.

PubMed

Vargas, Marco Antonio; Britto, Jorge

2016-11-03

Characterization of the scientific and technological infrastructure in health and its interactions with the industrial sector provides key elements for understanding the dynamics of innovation in health. This study conducts an exploratory analysis of the potentialities and limitations associated with scientific and technological capabilities in the health area in Brazil and the different links between the scientific and industrial sectors in health. The analysis points to important growth in internationally indexed research output, especially in certain areas such as pharmaceutics, public health, genetics, morphology, physiology, and microbiology. There has also been important growth in research groups that interact with the industrial sector in selected areas of health. The study highlights the importance of building more solid and permanent bridges between companies, research institutions, and the health system, linking the knowledge developed in research institutions to the dynamics of the industrial sector in health. Resumo: A caracterização da infraestrutura científica e tecnológica na área da saúde e das suas formas de articulação com a base produtiva representam elementos centrais na compreensão da dinâmica de inovação em saúde. Este estudo faz uma análise exploratória sobre as potencialidades e limitações associadas às capacitações científicas e tecnológicas na área da saúde no Brasil e as formas de articulação entre a base científica e a base produtiva em saúde. A análise aponta para o crescimento expressivo da produção bibliográfica com circulação internacional no campo da saúde, particularmente em determinadas áreas como farmácia, saúde coletiva, genética, morfologia, fisiologia e microbiologia. Além disso, observa-se um crescimento expressivo dos grupos de pesquisa com relacionamentos com o setor produtivo em áreas selecionadas da saúde. Destaca-se a importância da construção de pontes mais sólidas e permanentes entre empresas, instituições de pesquisa e sistema de saúde, articulando-se o conhecimento desenvolvido em instituições de pesquisa à dinamização da base produtiva em saúde.

Molecular modeling and cytotoxicity of diffractaic acid: HP-β-CD inclusion complex encapsulated in microspheres.

PubMed

Silva, Camilla V N S; Barbosa, Jéssica A P; Ferraz, Milena S; Silva, Nicácio H; Honda, Neli K; Rabello, Marcelo M; Hernandes, Marcelo Z; Bezerra, Beatriz P; Cavalcanti, Isabella M F; Ayala, Alejandro P; Santos, Noemia P S; Santos-Magalhães, Nereide S

2016-11-01

In this pioneer study, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was used to improve the solubility of the diffractaic acid (DA) via inclusion complex (DA:HP-β-CD). Subsequently, DA:HP-β-CD was incorporated into poly-ε-caprolactone (PCL) microspheres (DA:HP-β-CD-MS). Microspheres containing DA (DA-MS) or DA:HP-β-CD (DA:HP-β-CD-MS) were prepared using the multiple W/O/W emulsion-solvent evaporation technique. The phase-solubility diagram of DA in HP-β-CD (10-50mM) showed an A L type curve with a stability constant K 1:1 =821M -1 . 1 H NMR, FTIR, X-ray diffraction and thermal analysis showed changes in the molecular environment of DA in DA:HP-β-CD. The molecular modeling approach suggests a guest-host complex formation between the carboxylic moiety of both DA and the host (HP-β-CD). The mean particle size of the microspheres were ∅ DA-MS =5.23±1.65μm and ∅ DA:HP-β-CD-MS =4.11±1.39μm, respectively. The zeta potential values of the microspheres were ζ DA-MS =-7.85±0.32mV and ζ DA:HP-β-CD-MS =-6.93±0.46mV. Moreover, the encapsulation of DA:HP-β-CD into microspheres resulted in a more slower release (k 2 =0.042±0.001; r 2 =0.996) when compared with DA-MS (k 2 =0.183±0.005; r 2 =0.996). The encapsulation of DA or DA:HP-β-CD into microspheres reduced the cytotoxicity of DA (IC 50 =43.29μM) against Vero cells (IC 50 of DA-MS=108.48μM and IC 50 of DA:HP-β-CD-MS=142.63μM). Copyright © 2016 Elsevier B.V. All rights reserved.

Methamphetamine-induced neurotoxicity disrupts pharmacologically evoked dopamine transients in the dorsomedial and dorsolateral striatum.

PubMed

Robinson, John D; Howard, Christopher D; Pastuzyn, Elissa D; Byers, Diane L; Keefe, Kristen A; Garris, Paul A

2014-08-01

Phasic dopamine (DA) signaling, during which burst firing by DA neurons generates short-lived elevations in extracellular DA in terminal fields called DA transients, is implicated in reinforcement learning. Disrupted phasic DA signaling is proposed to link DA depletions and cognitive-behavioral impairment in methamphetamine (METH)-induced neurotoxicity. Here, we further investigated this disruption by assessing effects of METH pretreatment on DA transients elicited by a drug cocktail of raclopride, a D2 DA receptor antagonist, and nomifensine, an inhibitor of the dopamine transporter (DAT). One advantage of this approach is that pharmacological activation provides a large, high-quality data set of transients elicited by endogenous burst firing of DA neurons for analysis of regional differences and neurotoxicity. These pharmacologically evoked DA transients were measured in the dorsomedial (DM) and dorsolateral (DL) striatum of urethane-anesthetized rats by fast-scan cyclic voltammetry. Electrically evoked DA levels were also recorded to quantify DA release and uptake, and DAT binding was determined by means of autoradiography to index DA denervation. Pharmacologically evoked DA transients in intact animals exhibited a greater amplitude and frequency and shorter duration in the DM compared to the DL striatum, despite similar pre- and post-drug assessments of DA release and uptake in both sub-regions as determined from the electrically evoked DA signals. METH pretreatment reduced transient activity. The most prominent effect of METH pretreatment on transients across striatal sub-region was decreased amplitude, which mirrored decreased DAT binding and was accompanied by decreased DA release. Overall, these results identify marked intrastriatal differences in the activity of DA transients that appear independent of presynaptic mechanisms for DA release and uptake and further support disrupted phasic DA signaling mediated by decreased DA release in rats with METH-induced neurotoxicity.

Anti-inflammatory action of high molecular weight Mytilus edulis hydrolysates fraction in LPS-induced RAW264.7 macrophage via NF-κB and MAPK pathways.

PubMed

Kim, Young-Sang; Ahn, Chang-Bum; Je, Jae-Young

2016-07-01

Anti-inflammatory Mytilus edulis hydrolysates (MEHs) were prepared by peptic hydrolysis and MEH was further fractionated into three fractions based on molecular weight, namely >5kDa, 1-5kDa, and <1kDa. The >5kDa peptide fraction exerted the highest nitric oxide (NO) inhibitory activity and inhibited prostaglandin E2 (PGE2) secretion in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Pretreatment with the >5kDa peptide fraction markedly inhibited LPS-stimulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and gene expressions. Stimulation by LPS induced the production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and -1β (IL-1β), whereas co-treatment with the >5kDa peptide fraction suppressed pro-inflammatory cytokine production. The >5kDa peptide fraction inhibited the translocation of NF-κB (nuclear factor-kappa B) through the prevention of IκBα (inhibitory factor kappa B alpha) phosphorylation and degradation and also inhibited the MAPK signaling pathway in LPS-stimulated RAW264.7 macrophages. Copyright © 2016 Elsevier Ltd. All rights reserved.

Revisiting shape selectivity in liquid chromatography for polycyclic aromatic hydrocarbons (PAHs) - six-ring and seven-ring Cata-condensed PAH isomers of molecular mass 328 Da and 378 Da.

PubMed

Oña-Ruales, Jorge O; Sander, Lane C; Wilson, Walter B; Wise, Stephen A

2018-01-01

The relationship of reversed-phase liquid chromatography (RPLC) retention on a polymeric C 18 stationary phase and the shape of polycyclic aromatic hydrocarbons (PAHs) was investigated for three-ring to seven-ring cata-condensed isomers. We report the first RPLC separation for six-ring and seven-ring cata-condensed PAH isomers. Correlations of LC retention and shape parameters (length-to-breath ratio, L/B and thickness, T) were investigated for 2 three-ring isomers (molecular mass 178 Da), 5 four-ring isomers (molecular mass 228 Da), 11 five-ring isomers (molecular mass 278 Da), 17 six-ring isomers (molecular mass 328 Da), and 20 seven-ring isomers (molecular mass 378 Da). Significant linear correlations were found for all isomer groups (r = 0.71 to 0.94). Nonplanarity of the PAH isomers was found to influence retention (i.e., nonplanar isomers eluting earlier than expected based on L/B) and linear correlations of retention vs. T for isomer groups containing nonplanar isomers were significant (r = 0.71 to 0.86). Graphical abstract.

Striatal dopamine neurotransmission: regulation of release and uptake

PubMed Central

Sulzer, David; Cragg, Stephanie J.; Rice, Margaret E.

2016-01-01

Dopamine (DA) transmission is governed by processes that regulate release from axonal boutons in the forebrain and the somatodendritic compartment in midbrain, and by clearance by the DA transporter, diffusion, and extracellular metabolism. We review how axonal DA release is regulated by neuronal activity and by autoreceptors and heteroreceptors, and address how quantal release events are regulated in size and frequency. In brain regions densely innervated by DA axons, DA clearance is due predominantly to uptake by the DA transporter, whereas in cortex, midbrain, and other regions with relatively sparse DA inputs, the norepinephrine transporter and diffusion are involved. We discuss the role of DA uptake in restricting the sphere of influence of DA and in temporal accumulation of extracellular DA levels upon successive action potentials. The tonic discharge activity of DA neurons may be translated into a tonic extracellular DA level, whereas their bursting activity can generate discrete extracellular DA transients. PMID:27141430

Asymptomatic Elite Adolescent Tennis Players' Signs of Tendinosis in Their Dominant Shoulder Compared With Their Nondominant Shoulder

PubMed Central

Johansson, Fredrik R.; Skillgate, Eva; Adolfsson, Anders; Jenner, Göran; DeBri, Edin; Swärdh, Leif; Cools, Ann M.

2015-01-01

Context Tennis is an asymmetric overhead sport with specific muscle-activation patterns, especially eccentrically in the rotator cuff. Magnetic resonance imaging (MRI) findings in asymptomatic adolescent elite tennis players have not previously been reported. Objective The first aim of the study was to describe MRI findings regarding adaptations or abnormalities, as well as muscle cross-sectional area (CSA), of the rotator cuff. The second aim of the study was to investigate the rotator cuff based on the interpretation of the MRI scans as normal versus abnormal, with the subdivision based on the grade of tendinosis, and its association with eccentric rotator cuff strength in the dominant arm (DA) of the asymptomatic elite adolescent tennis player. Setting Testing environment at the radiology department of Medicinsk Röntgen AB. Patients or Other Participants Thirty-five asymptomatic elite tennis players (age = 17.4 ± 2.7 years) were selected based on ranking and exposure time. Intervention(s) We assessed MRI scans and measured the CSA of the rotator cuff muscle. The non-DA (NDA) was used as a control. In addition, eccentric testing of the external rotators of the DA was performed with a handheld dynamometer. Results The DA and NDA displayed different frequencies of infraspinatus tendinosis (grade 1 changes) (P < .05). Rotator cuff measurements revealed larger infraspinatus and teres minor CSA (P < .05) in the DA than in the NDA. Mean eccentric external-rotation strength in the DA stratified by normal tendon and tendinosis was not different between groups (P = .723). Conclusions Asymptomatic adolescent elite tennis players demonstrated infraspinatus tendinosis more frequently in the DA than in the NDA. Clinicians must recognize these tendon changes in order to modify conditioning and performance programs appropriately. PMID:26651279

75 FR 52292 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-25

... Industries GmbH Models DA 40 and DA 40F Airplanes AGENCY: Federal Aviation Administration (FAA), Department... new airworthiness directive (AD) for all Diamond Aircraft Industries GmbH Models DA 40 and DA 40F... received information from Diamond Aircraft Industries GmbH that the Models DA 40 and DA 40F airplanes have...

77 FR 54800 - Airworthiness Directives; Diamond Aircraft Industries GmbH Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-06

... airworthiness directive (AD) for certain Diamond Aircraft Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG... products. The MCAI states: During conversion of a DA 42 to a DA 42 NG, voids were detected in the adhesive... the following Diamond Aircraft Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG airplanes...

Highly sensitive and selective electrochemical dopamine sensing properties of multilayer graphene nanobelts

NASA Astrophysics Data System (ADS)

Karthick Kannan, Padmanathan; Moshkalev, Stanislav A.; Sekhar Rout, Chandra

2016-02-01

In the present study, we report the electrochemical sensing property of multi-layer graphene nanobelts (GNBs) towards dopamine (DA). GNBs are synthesized from natural graphite and characterized by using techniques like field-emission scanning electron microscopy, atomic force microscopy and Raman spectroscopy. An electrochemical sensor based on GNBs is developed for the detection of DA. From the cyclic voltammetry and amperometry studies, it is found that GNBs possess excellent electrocatalytic activity towards DA molecules. The developed DA sensor showed a sensitivity value of 0.95 μA μM-1 cm-2 with a linear range of 2 μM to 0.2 mM. The interference data exhibited that GNB is highly selective to DA even in the presence of common interfering species like ascorbic acid, uric acid, glucose and lactic acid.

Highly sensitive and selective electrochemical dopamine sensing properties of multilayer graphene nanobelts.

PubMed

Kannan, Padmanathan Karthick; Moshkalev, Stanislav A; Rout, Chandra Sekhar

2016-02-19

In the present study, we report the electrochemical sensing property of multi-layer graphene nanobelts (GNBs) towards dopamine (DA). GNBs are synthesized from natural graphite and characterized by using techniques like field-emission scanning electron microscopy, atomic force microscopy and Raman spectroscopy. An electrochemical sensor based on GNBs is developed for the detection of DA. From the cyclic voltammetry and amperometry studies, it is found that GNBs possess excellent electrocatalytic activity towards DA molecules. The developed DA sensor showed a sensitivity value of 0.95 μA μM(-1) cm(-2) with a linear range of 2 μM to 0.2 mM. The interference data exhibited that GNB is highly selective to DA even in the presence of common interfering species like ascorbic acid, uric acid, glucose and lactic acid.

Physical Properties and Stability of Soft Gelled Chitosan-Based Nanoparticles.

PubMed

Goycoolea, Francisco M; Brunel, Fabrice; Gueddari, Nour E El; Coggiola, Anna; Lollo, Giovanna; Moerschbacher, Bruno M; Remuñán-López, Carmen; Delair, Thierry; Domard, Alain; Alonso, María J

2016-12-01

We addressed the role of the degree of acetylation (DA) and of M w of chitosan (CS) on the physical characteristics and stability of soft nanoparticles obtained through either ionic cross-linking with sodium tripolyphosphate (TPP), or reverse emulsion/gelation. Each of these methods affords nanoparticles (NPs) or nanogels (NGs), respectively. The size of CS-TPP NPs comprising CS of high M w (≈123-266 kDa) increases with DA (≈1.6%-56%), while it do not change for CS of low M w (≈11-13 kDa); the zeta potential (ζ) decreases with DA regardless of M w (ζ ≈+34.6 ± 2.6 to ≈+25.2 + 0.6 mV) and the NPs appear as spheres in transmission electron microscopy. Stability in various cell culture media (pH 7.4 at 37 °C) is greater for NPs made with CS of DA ≥ 27%. In turn, NGs exhibit larger sizes (520 ± 32 to 682 ± 27 nm) than do CS-TPP NPs, and can only be formed with CS of DA < 30%. The average diameter size for these NGs shows a monotonic increase with CS's M w . The physical properties and stability of these systems in biological media depend mostly on the DA of CS and its influence on the balance between hydrophilic/hydrophobic interactions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Safety and usage of darbepoetin alfa in children with chronic kidney disease: prospective registry study.

PubMed

Schaefer, Franz; Hoppe, Bernd; Jungraithmayr, Therese; Klaus, Günter; Pape, Lars; Farouk, Mourad; Addison, Janet; Manamley, Nick; Vondrak, Karel

2016-03-01

Limited prospective data are available on the long-term safety of darbepoetin alfa (DA) for treating anemia in children with chronic kidney disease (CKD). In this prospective, phase IV, observational registry study, children ≤16 years of age with CKD anemia and receiving DA were observed for ≤2 years. Adverse events (AEs), DA dosing, hemoglobin (Hb) concentrations, and transfusions were recorded. A total of 319 patients were included in the analysis (mean age, 9.1 years), 158 (49.5%) of whom were on dialysis at study entry. Of 434 serious AEs reported in 162 children, the most common were peritonitis (10.0%), gastroenteritis (6.0%), and hypertension (4.1%). Six patients (1.9%) died (unrelated to DA). Four patients (1.3%) experienced six serious adverse drug reactions. The geometric mean DA dose range was 1.4-2.0 μg/kg/month. Mean baseline Hb concentration was 11.1 g/dl; mean values for children receiving and not receiving dialysis at baseline ranged between 10.9 and 11.5 g/dl and 11.2-11.7 g/dl, respectively. Overall, 48 patients (15.0%) received ≥1 transfusion. No new safety signals for DA were identified in children receiving DA for CKD anemia for ≤2 years. Based on Hb concentrations and transfusion requirements, DA was effective at managing anemia in these patients.

Electrocatalytic oxidation of dopamine based on non-covalent functionalization of manganese tetraphenylporphyrin/reduced graphene oxide nanocomposite.

PubMed

Sakthinathan, Subramanian; Lee, Hsin Fang; Chen, Shen-Ming; Tamizhdurai, P

2016-04-15

In the present work, a reduced graphene oxide (RGO) supported manganese tetraphenylporphyrin (Mn-TPP) nanocomposite was electrochemically synthesized and used for the highly selective and sensitive detection of dopamine (DA). The nuclear magnetic resonance, scanning electron microscopy and elemental analysis were confirmed the successful formation of RGO/Mn-TPP nanocomposite. The prepared RGO/Mn-TPP nanocomposite modified electrode exhibited an enhanced electrochemical response to DA with less oxidation potential and enhanced response current. The electrochemical studies revealed that the oxidation of the DA at the composite electrode is a surface controlled process. The cyclic voltammetry, differential pulse voltammetry and amperometry methods were enable to detect DA. The working linear range of the electrode was observed from 0.3 to 188.8 μM, limit of detection was 8 nM and the sensitivity was 2.606 μA μM(-1) cm(-2). Here, the positively charged DA and negatively charged porphyrin modified RGO can accelerate the electrocatalysis of DA via electrostatic attraction, while the negatively charged ascorbic acid (AA) repulsed by the negatively charged electrode surface which supported for good selectivity. The good recovery results obtained for the determination of DA present in DA injection samples and human pathological sample further revealed the good practicality of RGO/Mn-TPP nanocomposite film modified electrode. Copyright © 2016 Elsevier Inc. All rights reserved.

The Behavioral Pharmacology of Effort-related Choice Behavior: Dopamine, Adenosine and Beyond

PubMed Central

Salamone, John D; Correa, Merce; Nunes, Eric J; Randall, Patrick A; Pardo, Marta

2012-01-01

For many years, it has been suggested that drugs that interfere with dopamine (DA) transmission alter the “rewarding” impact of primary reinforcers such as food. Research and theory related to the functions of mesolimbic DA are undergoing a substantial conceptual restructuring, with the traditional emphasis on hedonia and primary reward yielding to other concepts and lines of inquiry. The present review is focused upon the involvement of nucleus accumbens DA in effort-related choice behavior. Viewed from the framework of behavioral economics, the effects of accumbens DA depletions and antagonism on food-reinforced behavior are highly dependent upon the work requirements of the instrumental task, and DA-depleted rats show a heightened sensitivity to response costs, especially ratio requirements. Moreover, interference with accumbens DA transmission exerts a powerful influence over effort-related choice behavior. Rats with accumbens DA depletions or antagonism reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and show increased selection of low reinforcement/low cost options. Nucleus accumbens DA and adenosine interact in the regulation of effort-related functions, and other brain structures (anterior cingulate cortex, amygdala, ventral pallidum) also are involved. Studies of the brain systems regulating effort-based processes may have implications for understanding drug abuse, as well as symptoms such as psychomotor slowing, fatigue or anergia in depression and other neurological disorders. PMID:22287808

The behavioral pharmacology of effort-related choice behavior: dopamine, adenosine and beyond.

PubMed

Salamone, John D; Correa, Merce; Nunes, Eric J; Randall, Patrick A; Pardo, Marta

2012-01-01

For many years, it has been suggested that drugs that interfere with dopamine (DA) transmission alter the "rewarding" impact of primary reinforcers such as food. Research and theory related to the functions of mesolimbic DA are undergoing a substantial conceptual restructuring, with the traditional emphasis on hedonia and primary reward yielding to other concepts and lines of inquiry. The present review is focused upon the involvement of nucleus accumbens DA in effort-related choice behavior. Viewed from the framework of behavioral economics, the effects of accumbens DA depletions and antagonism on food-reinforced behavior are highly dependent upon the work requirements of the instrumental task, and DA-depleted rats show a heightened sensitivity to response costs, especially ratio requirements. Moreover, interference with accumbens DA transmission exerts a powerful influence over effort-related choice behavior. Rats with accumbens DA depletions or antagonism reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and show increased selection of low reinforcement/low cost options. Nucleus accumbens DA and adenosine interact in the regulation of effort-related functions, and other brain structures (anterior cingulate cortex, amygdala, ventral pallidum) also are involved. Studies of the brain systems regulating effort-based processes may have implications for understanding drug abuse, as well as symptoms such as psychomotor slowing, fatigue or anergia in depression and other neurological disorders.

Single oral dose pharmacokinetics of decursin and decursinol angelate in healthy adult men and women.

PubMed

Zhang, Jinhui; Li, Li; Hale, Thomas W; Chee, Wayne; Xing, Chengguo; Jiang, Cheng; Lü, Junxuan

2015-01-01

The ethanol extract of Angelica gigas Nakai (AGN) root has promising anti-cancer and other bioactivities in rodent models. It is currently believed that the pyranocoumarin isomers decursin (D) and decursinol angelate (DA) contribute to these activities. We and others have documented that D and DA were rapidly converted to decursinol (DOH) in rodents. However, our in vitro metabolism studies suggested that D and DA might be metabolized differently in humans. To test this hypothesis and address a key question for human translatability of animal model studies of D and DA or AGN extract, we conducted a single oral dose human pharmacokinetic study of D and DA delivered through an AGN-based dietary supplement Cogni.Q (purchased from Quality of Life Labs, Purchase, NY) in twenty healthy subjects, i.e., 10 men and 10 women, each consuming 119 mg D and 77 mg DA from 4 vegicaps. Analyses of plasma samples using UHPLC-MS/MS showed mean time to peak concentration (Tmax) of 2.1, 2.4 and 3.3 h and mean peak concentration (Cmax) of 5.3, 48.1 and 2,480 nmol/L for D, DA and DOH, respectively. The terminal elimination half-life (t1/2) for D and DA was similar (17.4 and 19.3 h) and each was much longer than that of DOH (7.4 h). The mean area under the curve (AUC0-48h) for D, DA and DOH was estimated as 37, 335 and 27,579 h∙nmol/L, respectively. Gender-wise, men absorbed the parent compounds faster and took shorter time to reach DOH peak concentration. The human data supported an extensive conversion of D and DA to DOH, even though they metabolized DA slightly slower than rodents. Therefore, the data generated in rodent models concerning anti-cancer efficacy, safety, tissue distribution and pharmacodynamic biomarkers will likely be relevant for human translation. ClinicalTrials.gov NCT02114957.

Single Oral Dose Pharmacokinetics of Decursin and Decursinol Angelate in Healthy Adult Men and Women

PubMed Central

Zhang, Jinhui; Li, Li; Hale, Thomas W.; Chee, Wayne; Xing, Chengguo; Jiang, Cheng; Lü, Junxuan

2015-01-01

The ethanol extract of Angelica gigas Nakai (AGN) root has promising anti-cancer and other bioactivities in rodent models. It is currently believed that the pyranocoumarin isomers decursin (D) and decursinol angelate (DA) contribute to these activities. We and others have documented that D and DA were rapidly converted to decursinol (DOH) in rodents. However, our in vitro metabolism studies suggested that D and DA might be metabolized differently in humans. To test this hypothesis and address a key question for human translatability of animal model studies of D and DA or AGN extract, we conducted a single oral dose human pharmacokinetic study of D and DA delivered through an AGN-based dietary supplement Cogni.Q (purchased from Quality of Life Labs, Purchase, NY) in twenty healthy subjects, i.e., 10 men and 10 women, each consuming 119 mg D and 77 mg DA from 4 vegicaps. Analyses of plasma samples using UHPLC-MS/MS showed mean time to peak concentration (Tmax) of 2.1, 2.4 and 3.3 h and mean peak concentration (Cmax) of 5.3, 48.1 and 2,480 nmol/L for D, DA and DOH, respectively. The terminal elimination half-life (t1/2) for D and DA was similar (17.4 and 19.3 h) and each was much longer than that of DOH (7.4 h). The mean area under the curve (AUC0-48h) for D, DA and DOH was estimated as 37, 335 and 27,579 h∙nmol/L, respectively. Gender-wise, men absorbed the parent compounds faster and took shorter time to reach DOH peak concentration. The human data supported an extensive conversion of D and DA to DOH, even though they metabolized DA slightly slower than rodents. Therefore, the data generated in rodent models concerning anti-cancer efficacy, safety, tissue distribution and pharmacodynamic biomarkers will likely be relevant for human translation. Trial Registration ClinicalTrials.gov NCT02114957 PMID:25695490

Carboxyl methylation of 21-23 kDa membrane proteins in intact neuroblastoma cells is increased with differentiation.

PubMed

Haklai, R; Kloog, Y

1990-01-01

Evidence is presented for specific enzymatic methylation of 21-23 kDa membrane proteins in intact neuroblastoma N1E 115 cells, which is increased in dimethylsulfoxide-induced differentiated cells. Methylation of these proteins has characteristics typical of enzymatic reactions in which base labile volatile methyl groups are incorporated into proteins, consistent with the formation of protein carboxyl methylesters. However, these methylesters of the 21-23 kDa proteins are relatively stable compared to other protein carboxyl methylesters. The 3-fold increase in methylated 21-23 kDa proteins in the differentiated cells suggest biological significance in differentiation of the cell membranes.

A network architecture for International Business Satellite communications

NASA Astrophysics Data System (ADS)

Takahata, Fumio; Nohara, Mitsuo; Takeuchi, Yoshio

Demand Assignment (DA) control is expected to be introduced in the International Business Satellte communications (IBS) network in order to cope with a growing international business traffic. The paper discusses the DA/IBS network from the viewpoints of network configuration, satellite channel configuration and DA control. The network configuration proposed here consists of one Central Station with network management function and several Network Coordination Stations with user management function. A satellite channel configuration is also presented along with a tradeoff study on transmission bit rate, high power amplifier output power requirement, and service quality. The DA control flow and protocol based on CCITT Signalling System No. 7 are also proposed.

METHAMPHETAMINE-INDUCED NEUROTOXICITY DISRUPTS PHARMACOLOGICALLY EVOKED DOPAMINE TRANSIENTS IN THE DORSOMEDIAL AND DORSOLATERAL STRIATUM

PubMed Central

Robinson, John D.; Howard, Christopher D.; Pastuzyn, Elissa D.; Byers, Diane L.; Keefe, Kristen A.; Garris, Paul A.

2014-01-01

Phasic dopamine (DA) signaling, during which burst firing by dopamine neurons generates short-lived elevations in extracellular DA in terminal fields called DA transients, is implicated in reinforcement learning. Disrupted phasic DA signaling is proposed to link DA depletions and cognitive-behavioral impairment in methamphetamine (METH)-induced neurotoxicity. Here we further investigated this disruption by assessing effects of METH pretreatment on DA transients elicited by a drug cocktail of raclopride, a D2 DA receptor antagonist, and nomifensine, an inhibitor of the dopamine transporter (DAT). One advantage of this approach is that pharmacological activation provides a large, high-quality data set of transients elicited by endogenous burst firing of DA neurons for analysis of regional differences and neurotoxicity. These pharmacologically evoked DA transients were measured in the dorsomedial (DM) and dorsolateral (DL) striatum of urethane-anesthetized rats by fast-scan cyclic voltammetry. Electrically evoked DA levels were also recorded to quantify DA release and uptake, and DAT binding was determined by autoradiography to index DA denervation. Pharmacologically evoked DA transients in intact animals exhibited a greater amplitude and frequency and shorter duration in the DM compared to the DL striatum, despite similar pre- and post-drug assessments of DA release and uptake in both sub-regions as determined from the electrically evoked DA signals. METH pretreatment reduced transient activity. The most prominent effect of METH pretreatment on transients across striatal sub-region was decreased amplitude, which mirrored decreased DAT binding and was accompanied by decreased DA release. Overall, these results identify marked intrastriatal differences in the activity of DA transients that appear independent of presynaptic mechanisms for DA release and uptake and further support disrupted phasic DA signaling mediated by decreased DA release in rats with METH-induced neurotoxicity. PMID:24562969

Life events and quality of life in female patients with dermatitis artefacta: a comparative study with siblings and controls.

PubMed

El Kissi, Yousri; Chhoumi, Maha; Nakhli, Jaafar; Kenani, Nesrine; Denguezli, Mohamed; Nouira, Rafiaa; Ben Hadj Ali, Bechir

2014-10-01

If the severity of dermatitis artefacta (DA) is accepted by most authors, few published studies have sought to clarify its etiology and impact. It is in this context that this work aimed to compare Life Events (LE) and quality of life (QoL) scores in patients with DA, in their siblings and in control patients with other chronic dermatological diseases. This is a descriptive and comparative cross-sectional study carried out in the dermatology department of Farhat Hached hospital in Sousse, Tunisia. Thirty female patients diagnosed with DA according to DSM-IV criteria were retrospectively recruited. For each patient with DA, one of her sisters, the closest in age, was enrolled in the siblings group. The control group consisted of thirty female patients with other chronic dermatological diseases, matched with DA patients for age and duration of disease progression. Assessment was based on Paykel inventory for LE and on SF-36 for QoL. Compared to both control groups, DA patients reported more LE with more objective negative impact of these events and had a lower score and more often impaired mean global score of QoL. LE would have a role in the pathogenesis of DA which seems to alter the QoL of patients. These results could help to improve the understanding of DA and incite clinicians to focus not only on the diagnosis and treatment of DA but also on the impact of this disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Analysis of the mechanisms by which amphetamine releases dopamine from striatal dopaminergic neurons

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

Parker, E.M.

1987-01-01

The goals of the studies were (1) to determine the intraneuronal transmitter pools that contribute to the efflux of dopamine (DA) elicited by amphetamine (AMPH) and (2) to determine the biochemical mechanism by which AMPH increases DA efflux from dopaminergic neurons. AMPH increased the efflux of endogenous DA and decreased the electrically-evoked overflow of (/sup 3/H) acetylcholine (ACh) from superfused rabbit striatal slices. These effects were most pronounced when both vesicular DA stores and DA synthesis were intact. Therefore, extravesicular, newly synthesized DA and vesicular stores of DA contribute to AMPH-induced DA efflux. Simultaneous inhibition of monoamine oxidase (MAO) andmore » neuronal DA uptake did not increase the efflux of endogenous DA or inhibit the electrically-evoked overflow of (/sup 3/H)ACh to the same extent as AMPH. Hence, inhibition of MAO and neuronal DA uptake are probably not the major mechanisms by which AMPH increases DA efflux. The AMPH-induced efflux of endogenous or (/sup 3/H)DA was blocked by inhibitors of neuronal DA uptake.« less

DeDaL: Cytoscape 3 app for producing and morphing data-driven and structure-driven network layouts.

PubMed

Czerwinska, Urszula; Calzone, Laurence; Barillot, Emmanuel; Zinovyev, Andrei

2015-08-14

Visualization and analysis of molecular profiling data together with biological networks are able to provide new mechanistic insights into biological functions. Currently, it is possible to visualize high-throughput data on top of pre-defined network layouts, but they are not always adapted to a given data analysis task. A network layout based simultaneously on the network structure and the associated multidimensional data might be advantageous for data visualization and analysis in some cases. We developed a Cytoscape app, which allows constructing biological network layouts based on the data from molecular profiles imported as values of node attributes. DeDaL is a Cytoscape 3 app, which uses linear and non-linear algorithms of dimension reduction to produce data-driven network layouts based on multidimensional data (typically gene expression). DeDaL implements several data pre-processing and layout post-processing steps such as continuous morphing between two arbitrary network layouts and aligning one network layout with respect to another one by rotating and mirroring. The combination of all these functionalities facilitates the creation of insightful network layouts representing both structural network features and correlation patterns in multivariate data. We demonstrate the added value of applying DeDaL in several practical applications, including an example of a large protein-protein interaction network. DeDaL is a convenient tool for applying data dimensionality reduction methods and for designing insightful data displays based on data-driven layouts of biological networks, built within Cytoscape environment. DeDaL is freely available for downloading at http://bioinfo-out.curie.fr/projects/dedal/.

A critical evaluation of an asymmetrical flow field-flow fractionation system for colloidal size characterization of natural organic matter.

PubMed

Zhou, Zhengzhen; Guo, Laodong

2015-06-19

Colloidal retention characteristics, recovery and size distribution of model macromolecules and natural dissolved organic matter (DOM) were systematically examined using an asymmetrical flow field-flow fractionation (AFlFFF) system under various membrane size cutoffs and carrier solutions. Polystyrene sulfonate (PSS) standards with known molecular weights (MW) were used to determine their permeation and recovery rates by membranes with different nominal MW cutoffs (NMWCO) within the AFlFFF system. Based on a ≥90% recovery rate for PSS standards by the AFlFFF system, the actual NMWCOs were determined to be 1.9 kDa for the 0.3 kDa membrane, 2.7 kDa for the 1 kDa membrane, and 33 kDa for the 10 kDa membrane, respectively. After membrane calibration, natural DOM samples were analyzed with the AFlFFF system to determine their colloidal size distribution and the influence from membrane NMWCOs and carrier solutions. Size partitioning of DOM samples showed a predominant colloidal size fraction in the <5 nm or <10 kDa size range, consistent with the size characteristics of humic substances as the main terrestrial DOM component. Recovery of DOM by the AFlFFF system, as determined by UV-absorbance at 254 nm, decreased significantly with increasing membrane NMWCO, from 45% by the 0.3 kDa membrane to 2-3% by the 10 kDa membrane. Since natural DOM is mostly composed of lower MW substances (<10 kDa) and the actual membrane cutoffs are normally larger than their manufacturer ratings, a 0.3 kDa membrane (with an actual NMWCO of 1.9 kDa) is highly recommended for colloidal size characterization of natural DOM. Among the three carrier solutions, borate buffer seemed to provide the highest recovery and optimal separation of DOM. Rigorous calibration with macromolecular standards and optimization of system conditions are a prerequisite for quantifying colloidal size distribution using the flow field-flow fractionation technique. In addition, the coupling of AFlFFF with fluorescence EEMs could provide new insights into DOM heterogeneity in different colloidal size fractions. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification of native angiotensin-I converting enzyme inhibitory peptides in commercial soybean based infant formulas using HPLC-Q-ToF-MS.

PubMed

Puchalska, Patrycja; Concepción García, M; Luisa Marina, M

2014-08-15

This work evaluates, the presence of native antihypertensive peptides in five soybean-based infant formulas (SBIFs). SBIFs peptide extracts (<10 kDa) and their sub-fractions (5-10 kDa, 3-5 kDa, and <3 kDa) from a variety of samples were obtained by ultrafiltration and ACE inhibitory activity was determined. The highest activities were observed in the smaller (<5 kDa) peptide fractions. A set of peptides present in various SBIFs were studied, and identified using HPLC-Q-ToF-MS. Despite ACE inhibitory activity decreasing after in vitro gastrointestinal digestion, it still remained at a high value (IC50 values of 18.2±0.1 and 4.9±0.1 μg/mL). Peptides resisting the action of gastrointestinal enzymes were identified and compared to previously identified peptides, highlighting the presence of peptide RPSYT. This peptide was synthesised, its antihypertensive and antioxidant activity were evaluated, and its resistance to in vitro gastrointestinal digestion and to high processing temperatures were studied. Copyright © 2014 Elsevier Ltd. All rights reserved.

The major histocompatibility complex genes impact pain response in DA and DA.1U rats.

PubMed

Guo, Yuan; Yao, Fan-Rong; Cao, Dong-Yuan; Li, Li; Wang, Hui-Sheng; Xie, Wen; Zhao, Yan

2015-08-01

Our recent studies have shown that the difference in basal pain sensitivity to mechanical and thermal stimulation between Dark-Agouti (DA) rats and a novel congenic DA.1U rats is major histocompatibility complex (MHC) genes dependent. In the present study, we further used DA and DA.1U rats to investigate the role of MHC genes in formalin-induced pain model by behavioral, electrophysiological and immunohistochemical methods. Behavioral results showed biphasic nociceptive behaviors increased significantly following the intraplantar injection of formalin in the hindpaw of DA and DA.1U rats. The main nociceptive behaviors were lifting and licking, especially in DA rats (P<0.001 and P<0.01). The composite pain scores (CPS) in DA rats were significantly higher than those in DA.1U rats in both phases of the formalin test (P<0.01). Electrophysiological results also showed the biphasic increase in discharge rates of C and Aδ fibers of L5 dorsal root in the two strains, and the net change of the discharge rate of DA rats was significantly higher than that of DA.1U rats (P<0.05). The mechanical thresholds decreased after formalin injection in both strains (P<0.01), and the net change in the mechanical threshold in DA was greater than that in DA.1U rats (P<0.05). The expression of RT1-B, representation of MHC class II molecule, in laminae I-II of L4/5 spinal cord in DA rats was significantly higher than that in DA.1U rats in the respective experimental group (P<0.05). These results suggested that both DA and DA.1U rats exhibited nociceptive responses in formalin-induced pain model and DA rats were more sensitive to noxious chemical stimulus than DA.1U rats, indicating that MHC genes might contribute to the difference in pain sensitivity. Copyright © 2015 Elsevier Inc. All rights reserved.

The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

PubMed

Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

2016-02-01

A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes. © 2016 John Wiley & Sons Australia, Ltd.

Anion-Driven Self-Assembly Processes Based on Halogen-Bonding

DTIC Science & Technology

2007-07-10

23993041 Fax: +39-02-23993180 E-mail: pierangelo.metrangolo@polimi.it Sede Leonardo : Piazza L.Da Vinci , 32 – 20133 Milano Tel. ++39-02...02-23993180 E-mail: pierangelo.metrangolo@polimi.it Sede Leonardo : Piazza L.Da Vinci , 32 – 20133 Milano Tel. ++39-02 2399.3200 Fax ++39-02...Pierangelo Metrangolo Ph. +39-02-23993041 Fax: +39-02-23993180 E-mail: pierangelo.metrangolo@polimi.it Sede Leonardo : Piazza L.Da Vinci , 32

METHAMPHETAMINE-INDUCED NEUROTOXICITY DISRUPTS NATURALLY OCCURRING PHASIC DOPAMINE SIGNALING

PubMed Central

Howard, Christopher D.; Daberkow, David P.; Ramsson, Eric S.; Keefe, Kristen A.; Garris, Paul A.

2013-01-01

Methamphetamine (METH) is a highly addictive drug that is also neurotoxic to central dopamine (DA) systems. Although striatal DA depletions induced by METH are associated with behavioral and cognitive impairments, the link between these phenomena remains poorly understood. Previous work in both METH-pretreated animals and the 6-hydroxydopamine model of Parkinson’s disease suggests that a disruption of phasic DA signaling, which is important for learning and goal-directed behavior, may be such a link. However, prior studies used electrical stimulation to elicit phasic-like DA responses and were also performed under anesthesia, which alters DA neuron activity and presynaptic function. Here we investigated the consequences of METH-induced DA terminal loss on both electrically evoked phasic-like DA signals and so-called “spontaneous” phasic DA transients measured by voltammetry in awake rats. Not ostensibly attributable to discrete stimuli, these sub-second DA changes may play a role in enhancing reward-cue associations. METH-pretreatment reduced tissue DA content in the dorsomedial striatum and nucleus accumbens by ~55%. Analysis of phasic-like DA responses elicited by reinforcing stimulation revealed that METH pretreatment decreased their amplitude and underlying mechanisms for release and uptake to a similar degree as DA content in both striatal subregions. Most importantly, characteristics of DA transients were altered by METH-induced DA terminal loss, with amplitude and frequency decreased and duration increased. These results demonstrate for the first time that denervation of DA neurons alters naturally occurring DA transients and are consistent with diminished phasic DA signaling as a plausible mechanism linking METH-induced striatal DA depletions and cognitive deficits. PMID:23574406

Are regional variations in activity of dispatcher-assisted cardiopulmonary resuscitation associated with out-of-hospital cardiac arrests outcomes? A nation-wide population-based cohort study.

PubMed

Nishi, Taiki; Kamikura, Takahisa; Funada, Akira; Myojo, Yasuhiro; Ishida, Tetsuya; Inaba, Hideo

2016-01-01

Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) impacts the rates of bystander CPR (BCPR) and survival after out-of-hospital cardiac arrests (OHCAs). This study aimed to elucidate whether regional variations in indexes for BCPR and emergency medical service (EMS) may be associated with OHCA outcomes. We conducted a population-based observational study involving 157,093 bystander-witnessed, resuscitation-attempted OHCAs without physician involvement between 2007 and 2011. For each index of BCPR and EMS, we classified the 47 prefectures into the following three groups: advanced, intermediate, and developing regions. Nominal logit analysis followed by multivariable logistic regression including OHCA backgrounds was employed to examine the association between neurologically favourable 1-month survival, and regional classifications based on BCPR- and EMS-related indexes. Logit analysis including all regional classifications revealed that the number of BLS training course participants per population or bystander's own performance of BCPR without DA-CPR was not associated with the survival. Multivariable logistic regression including the OHCA backgrounds known to be associated with survival (BCPR provision, arrest aetiology, initial rhythm, patient age, time intervals of witness-to-call and call-to-arrival at patient), the following regional classifications based on DA-CPR but not on EMS were associated with survival: sensitivity of DA-CPR [adjusted odds ratio (95% confidence intervals) for advanced region; those for intermediate region, with developing region as reference, 1.277 (1.131-1.441); 1.162 (1.058-1.277)]; the proportion of bystanders to follow DA-CPR [1.749 (1.554-1.967); 1.280 (1.188-1.380)]. Good outcomes of bystander-witnessed OHCAs correlate with regions having higher sensitivity of DA-CPR and larger proportion of bystanders to follow DA-CPR. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dopamine, Effort-Based Choice, and Behavioral Economics: Basic and Translational Research

PubMed Central

Salamone, John D.; Correa, Merce; Yang, Jen-Hau; Rotolo, Renee; Presby, Rose

2018-01-01

Operant behavior is not only regulated by factors related to the quality or quantity of reinforcement, but also by the work requirements inherent in performing instrumental actions. Moreover, organisms often make effort-related decisions involving economic choices such as cost/benefit analyses. Effort-based decision making is studied using behavioral procedures that offer choices between high-effort options leading to relatively preferred reinforcers vs. low effort/low reward choices. Several neural systems, including the mesolimbic dopamine (DA) system and other brain circuits, are involved in regulating effort-related aspects of motivation. Considerable evidence indicates that mesolimbic DA transmission exerts a bi-directional control over exertion of effort on instrumental behavior tasks. Interference with DA transmission produces a low-effort bias in animals tested on effort-based choice tasks, while increasing DA transmission with drugs such as DA transport blockers tends to enhance selection of high-effort options. The results from these pharmacology studies are corroborated by the findings from recent articles using optogenetic, chemogenetic and physiological techniques. In addition to providing important information about the neural regulation of motivated behavior, effort-based choice tasks are useful for developing animal models of some of the motivational symptoms that are seen in people with various psychiatric and neurological disorders (e.g., depression, schizophrenia, Parkinson’s disease). Studies of effort-based decision making may ultimately contribute to the development of novel drug treatments for motivational dysfunction. PMID:29628879

Dopamine, Effort-Based Choice, and Behavioral Economics: Basic and Translational Research.

PubMed

Salamone, John D; Correa, Merce; Yang, Jen-Hau; Rotolo, Renee; Presby, Rose

2018-01-01

Operant behavior is not only regulated by factors related to the quality or quantity of reinforcement, but also by the work requirements inherent in performing instrumental actions. Moreover, organisms often make effort-related decisions involving economic choices such as cost/benefit analyses. Effort-based decision making is studied using behavioral procedures that offer choices between high-effort options leading to relatively preferred reinforcers vs. low effort/low reward choices. Several neural systems, including the mesolimbic dopamine (DA) system and other brain circuits, are involved in regulating effort-related aspects of motivation. Considerable evidence indicates that mesolimbic DA transmission exerts a bi-directional control over exertion of effort on instrumental behavior tasks. Interference with DA transmission produces a low-effort bias in animals tested on effort-based choice tasks, while increasing DA transmission with drugs such as DA transport blockers tends to enhance selection of high-effort options. The results from these pharmacology studies are corroborated by the findings from recent articles using optogenetic, chemogenetic and physiological techniques. In addition to providing important information about the neural regulation of motivated behavior, effort-based choice tasks are useful for developing animal models of some of the motivational symptoms that are seen in people with various psychiatric and neurological disorders (e.g., depression, schizophrenia, Parkinson's disease). Studies of effort-based decision making may ultimately contribute to the development of novel drug treatments for motivational dysfunction.

Motivational states influence effort-based decision making in rats: the role of dopamine in the nucleus accumbens.

PubMed

Mai, Bettina; Sommer, Susanne; Hauber, Wolfgang

2012-03-01

Decision-making policies are subject to modulation by changing motivational states. However, so far, little is known about the neurochemical mechanisms that bridge motivational states with decision making. Here we examined whether dopamine (DA) in the nucleus accumbens core (AcbC) modulates the effects of motivational states on effort-based decision making. Using a cost-benefit T-maze task in rats, we examined the effects of AcbC DA depletions on effort-based decision making, in particular on the sensitivity of effort-based decision making to a shift from a hungry to a sated state. The results demonstrated that, relative to sham controls, rats with AcbC DA depletion in a hungry as well as in a sated state had a reduced preference for effortful but large-reward action. This finding provides further support for the notion that AcbC DA regulates how much effort to invest for rewards. Importantly, our results further revealed that effort-based decision making in lesioned rats, as in sham controls, was still sensitive to a shift from a hungry to a sated state; that is, their preferences for effortful large-reward actions became lower after a shift from a restricted to a free-feeding regimen. These finding indicate that AcbC DA is not necessarily involved in mediating the effects of a shift in motivational state on decision-making policies.

Comparative study of corn stover pretreated by dilute acid and cellulose solvent-based lignocellulose fractionation: Enzymatic hydrolysis, supramolecular structure, and substrate accessibility.

PubMed

Zhu, Zhiguang; Sathitsuksanoh, Noppadon; Vinzant, Todd; Schell, Daniel J; McMillan, James D; Zhang, Y-H Percival

2009-07-01

Liberation of fermentable sugars from recalcitrant biomass is among the most costly steps for emerging cellulosic ethanol production. Here we compared two pretreatment methods (dilute acid, DA, and cellulose solvent and organic solvent lignocellulose fractionation, COSLIF) for corn stover. At a high cellulase loading [15 filter paper units (FPUs) or 12.3 mg cellulase per gram of glucan], glucan digestibilities of the corn stover pretreated by DA and COSLIF were 84% at hour 72 and 97% at hour 24, respectively. At a low cellulase loading (5 FPUs per gram of glucan), digestibility remained as high as 93% at hour 24 for the COSLIF-pretreated corn stover but reached only approximately 60% for the DA-pretreated biomass. Quantitative determinations of total substrate accessibility to cellulase (TSAC), cellulose accessibility to cellulase (CAC), and non-cellulose accessibility to cellulase (NCAC) based on adsorption of a non-hydrolytic recombinant protein TGC were measured for the first time. The COSLIF-pretreated corn stover had a CAC of 11.57 m(2)/g, nearly twice that of the DA-pretreated biomass (5.89 m(2)/g). These results, along with scanning electron microscopy images showing dramatic structural differences between the DA- and COSLIF-pretreated samples, suggest that COSLIF treatment disrupts microfibrillar structures within biomass while DA treatment mainly removes hemicellulose. Under the tested conditions COSLIF treatment breaks down lignocellulose structure more extensively than DA treatment, producing a more enzymatically reactive material with a higher CAC accompanied by faster hydrolysis rates and higher enzymatic digestibility. (c) 2009 Wiley Periodicals, Inc.

Synthesizing a nano-composite of BSA-capped Au nanoclusters/graphitic carbon nitride nanosheets as a new fluorescent probe for dopamine detection.

PubMed

Guo, Xinrong; Wu, Fangying; Ni, Yongnian; Kokot, Serge

2016-10-26

A strong red fluorescent nanocomposite, consisting of graphite-like carbon nitride nanosheets (g-C 3 N 4 NSs) and serum albumin-capped Au nanoclusters (AuNCs), was synthesized. Dopamine (DA) can quench the red fluorescence of the nanocomposite, based on the Forster resonance energy transfer (FRET) mechanism. In this quenching process, the energy is transferred from the fluorescent g-C 3 N 4 NSs-AuNCs to the oxidized DA quinine molecules (DA is easily oxidated to form DA quinine in air). The red fluorescence emission at 420 nm decreases dramatically and the quenching ratio (F 0 - F)/F 0 is linearly related to the concentration of DA in the range of 0.05-8.0 μmol L -1 with a detection limit of 0.018 μmol L -1  (S/N = 3). Additionally, this sensor has a potential of application to assay the DA in the real samples, such as human serum and human urine. Copyright © 2016 Elsevier B.V. All rights reserved.

Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input-Output Mapping.

PubMed

Beier, Kevin T; Steinberg, Elizabeth E; DeLoach, Katherine E; Xie, Stanley; Miyamichi, Kazunari; Schwarz, Lindsay; Gao, Xiaojing J; Kremer, Eric J; Malenka, Robert C; Luo, Liqun

2015-07-30

Dopamine (DA) neurons in the midbrain ventral tegmental area (VTA) integrate complex inputs to encode multiple signals that influence motivated behaviors via diverse projections. Here, we combine axon-initiated viral transduction with rabies-mediated trans-synaptic tracing and Cre-based cell-type-specific targeting to systematically map input-output relationships of VTA-DA neurons. We found that VTA-DA (and VTA-GABA) neurons receive excitatory, inhibitory, and modulatory input from diverse sources. VTA-DA neurons projecting to different forebrain regions exhibit specific biases in their input selection. VTA-DA neurons projecting to lateral and medial nucleus accumbens innervate largely non-overlapping striatal targets, with the latter also sending extensive extra-striatal axon collaterals. Using electrophysiology and behavior, we validated new circuits identified in our tracing studies, including a previously unappreciated top-down reinforcing circuit from anterior cortex to lateral nucleus accumbens via VTA-DA neurons. This study highlights the utility of our viral-genetic tracing strategies to elucidate the complex neural substrates that underlie motivated behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

Experience with ATLAS MySQL PanDA database service

NASA Astrophysics Data System (ADS)

Smirnov, Y.; Wlodek, T.; De, K.; Hover, J.; Ozturk, N.; Smith, J.; Wenaus, T.; Yu, D.

2010-04-01

The PanDA distributed production and analysis system has been in production use for ATLAS data processing and analysis since late 2005 in the US, and globally throughout ATLAS since early 2008. Its core architecture is based on a set of stateless web services served by Apache and backed by a suite of MySQL databases that are the repository for all PanDA information: active and archival job queues, dataset and file catalogs, site configuration information, monitoring information, system control parameters, and so on. This database system is one of the most critical components of PanDA, and has successfully delivered the functional and scaling performance required by PanDA, currently operating at a scale of half a million jobs per week, with much growth still to come. In this paper we describe the design and implementation of the PanDA database system, its architecture of MySQL servers deployed at BNL and CERN, backup strategy and monitoring tools. The system has been developed, thoroughly tested, and brought to production to provide highly reliable, scalable, flexible and available database services for ATLAS Monte Carlo production, reconstruction and physics analysis.

Descent Advisor Preliminary Field Test

NASA Technical Reports Server (NTRS)

Green, Steven M.; Vivona, Robert A.; Sanford, Beverly

1995-01-01

A field test of the Descent Advisor (DA) automation tool was conducted at the Denver Air Route Traffic Control Center in September 1994. DA is being developed to assist Center controllers in the efficient management and control of arrival traffic. DA generates advisories, based on trajectory predictions, to achieve accurate meter-fix arrival times in a fuel efficient manner while assisting the controller with the prediction and resolution of potential conflicts. The test objectives were: (1) to evaluate the accuracy of DA trajectory predictions for conventional and flight-management system equipped jet transports, (2) to identify significant sources of trajectory prediction error, and (3) to investigate procedural and training issues (both air and ground) associated with DA operations. Various commercial aircraft (97 flights total) and a Boeing 737-100 research aircraft participated in the test. Preliminary results from the primary test set of 24 commercial flights indicate a mean DA arrival time prediction error of 2.4 seconds late with a standard deviation of 13.1 seconds. This paper describes the field test and presents preliminary results for the commercial flights.

A clinical evaluation denture adhesives used by patients with xerostomia.

PubMed

Bogucki, Zdzislaw A; Napadlek, Piotr; Dabrowa, Tomasz

2015-02-01

The purpose of study was to analyze the participants' opinions concerning the effectiveness of 6 denture adhesives (DA). The study group included 60 participants. Criteria for selecting the patients were as follows: reduced retention and stabilization of maxillary complete dentures and xerostomia. These features were evaluated on basis of clinical examination and standard sialometry tests (u-SFR). Retention of maxillary dentures was scored by modified Kapur index before application of DA. All participants were divided randomly into 6 groups regarding the use of the 6 DA during a 6-month period. After this time, participants completed an HRQL questionnaire. DA noticeably improved retention and stabilization of maxillary complete dentures. DA in the glue form had the best retention effectiveness in participants with xerostomia. These materials are difficult to clean from the denture base. The data are presented in tables and figures. The results of the study collected positive influence of adhesives on retention of dentures in xerostomia patients. The cleaning dentures and denture bearing tissues was difficult. DA help in the use of prostheses, but it is also necessary for the treatment of the causes and symptoms of xerostomia.

Effects of molindone on central dopaminergic neuronal activity and metabolism: similarity to other neuroleptics.

PubMed

Bunney, B S; Roth, R H; Aghajanian, G K

1975-01-01

The effect of molindone on the activity of dopaminergic (DA) neurons in the rat midbrain and on DA metabolism in the striatum and olfactory tubercles was studied using extracellular single unit recording and biochemical techniques respectively. Molindone in low intravenous doses (0.4-0.8 mg/kg) was found to reverse d-amphetamine and apomorphine induced depression of DA neurons and to block apomorphine induced depression of these cells. Molindone was also found to increase dopamine synthesis and dihydroxyphenylactic acid levels in the striatum and olfacotry tubercles. In all of these respects molindone behaves identically to most classical neuroleptics. However, unlike most antipsychotic drugs previously tested, molindone failed to increase the baseline firing rate of DA cells and blocked haloperidol induced increases in DA neuron activity. In this regard molindone most closely resembles thioridazine and clozapine. Possible mechanisms of action of molindone are discussed based on these findings.

Facile Synthesis of Molecularly Imprinted Graphene Quantum Dots for the Determination of Dopamine with Affinity-Adjustable.

PubMed

Zhou, Xi; Wang, Anqi; Yu, Chenfei; Wu, Shishan; Shen, Jian

2015-06-10

A facilely prepared fluorescence sensor was developed for dopamine (DA) determination based on polyindole/graphene quantum dots molecularly imprinted polymers (PIn/GQDs@MIPs). The proposed sensor exhibits a high sensitivity with a linear range of 5 × 10(-10) to 1.2 × 10(-6) M and the limit of detection as low as 1 × 10(-10) M in the determination of DA, which is probably due to the tailor-made imprinted cavities for binding DA thought hydrogen bonds between amine groups of DA and oxygen-containing groups of the novel composite. Furthermore, the prepared sensor can rebind DA in dual-type: a low affinity type (noncovalent interaction is off) and a high affinity type (noncovalent interaction is on), and the rebinding interaction can be adjusted by tuning the pH, which shows a unique potential for adjusting the binding interaction while keeping the specificity, allowing for wider applications.

Phasic dopamine release in the rat nucleus accumbens predicts approach and avoidance performance

PubMed Central

Gentry, Ronny N.; Lee, Brian; Roesch, Matthew R.

2016-01-01

Dopamine (DA) is critical for reward processing, but significantly less is known about its role in punishment avoidance. Using a combined approach-avoidance task, we measured phasic DA release in the nucleus accumbens (NAc) of rats during presentation of cues that predicted reward, punishment or neutral outcomes and investigated individual differences based on avoidance performance. Here we show that DA release within a single microenvironment is higher for reward and avoidance cues compared with neutral cues and positively correlated with poor avoidance behaviour. We found that DA release delineates trial-type during sessions with good avoidance but is non-selective during poor avoidance, with high release correlating with poor performance. These data demonstrate that phasic DA is released during cued approach and avoidance within the same microenvironment and abnormal processing of value signals is correlated with poor performance. PMID:27786172

Somatodendritic dopamine release: recent mechanistic insights

PubMed Central

Rice, Margaret E.; Patel, Jyoti C.

2015-01-01

Dopamine (DA) is a key transmitter in motor, reward and cogitative pathways, with DA dysfunction implicated in disorders including Parkinson's disease and addiction. Located in midbrain, DA neurons of the substantia nigra pars compacta project via the medial forebrain bundle to the dorsal striatum (caudate putamen), and DA neurons in the adjacent ventral tegmental area project to the ventral striatum (nucleus accumbens) and prefrontal cortex. In addition to classical vesicular release from axons, midbrain DA neurons exhibit DA release from their cell bodies and dendrites. Somatodendritic DA release leads to activation of D2 DA autoreceptors on DA neurons that inhibit their firing via G-protein-coupled inwardly rectifying K+ channels. This helps determine patterns of DA signalling at distant axonal release sites. Somatodendritically released DA also acts via volume transmission to extrasynaptic receptors that modulate local transmitter release and neuronal activity in the midbrain. Thus, somatodendritic release is a pivotal intrinsic feature of DA neurons that must be well defined in order to fully understand the physiology and pathophysiology of DA pathways. Here, we review recent mechanistic aspects of somatodendritic DA release, with particular emphasis on the Ca2+ dependence of release and the potential role of exocytotic proteins. PMID:26009764

β-Cyclodextrin functionalised gold nanoclusters as luminescence probes for the ultrasensitive detection of dopamine.

PubMed

Ban, Rui; Abdel-Halim, E S; Zhang, Jianrong; Zhu, Jun-Jie

2015-02-21

A novel luminescence probe based on mono-6-amino-β-cyclodextrin (NH2-β-CD) functionalised gold nanoclusters (β-CD-AuNC) was designed for dopamine (DA) detection. The NH2-β-CD molecules were conjugated onto the surface of 11-mercaptoundecanoic acid capped AuNCs (11-MUA-AuNC) via a carbodiimide coupling reaction. The integrity of the β-CD cavities was preserved on the surface of AuNCs and they retained their capability for molecular DA host-guest recognition. DA could be captured by the β-CD cavities to form an inclusion complex in which the oxidised DA could quench the fluorescence of the β-CD-AuNC probe by electron transfer. The probe could be used to quantify DA in the range of 5-1000 nM with a detection limit of 2 nM. This sensitivity was 1-2 orders of magnitude higher than that in previously reported methods. Interference by both ascorbic acid (AA) and uric acid (UA) was not observed. Therefore, the β-CD-AuNC probe could be directly used to determine the DA content in biological samples without further separation. This strategy was successfully applied to a DA assay in spiked human serum samples and it exhibited remarkable accuracy, sensitivity and selectivity.

Vi-da: vitiligo diagnostic assistance mobile application

NASA Astrophysics Data System (ADS)

Nugraha, G. A.; Nurhudatiana, A.; Bahana, R.

2018-03-01

Vitiligo is a skin disorder in which white patches of depigmentation appear on different parts of the body. Usually, patients come to hospitals or clinics to have their vitiligo conditions assessed. This can be very tiring to the patients, as vitiligo treatments usually take a relatively long period of time, which can range from months to years. To address this challenge, we present in this paper a prototype of an Android-based mobile application called Vi-DA, which stands for Vitiligo Diagnostic Assistance. Vi-DA consists of three subsystems, which are user sign-up subsystem, camera and image analysis subsystem, and progress report subsystem. The mobile application was developed in Java programming language and uses MySQL as the database system. Vi-DA adopts a vitiligo segmentation algorithm to segment input image into normal skin area, vitiligo skin area, and non-skin area. Results showed that Vi-DA gave comparable results to the previous system implemented in Matlab. User acceptance testing results also showed that all respondents agreed on the usefulness of the system and agreed to use Vi-DA again in the future. Vi-DA benefits both dermatologists and patients as not only a computer-aided diagnosis (CAD) tool but also as a smart application that can be used for self-assessment at home.

OpenDA-WFLOW framework for improving hydrologic predictions using distributed hydrologic models

NASA Astrophysics Data System (ADS)

Weerts, Albrecht; Schellekens, Jaap; Kockx, Arno; Hummel, Stef

2017-04-01

Data assimilation (DA) holds considerable potential for improving hydrologic predictions (Liu et al., 2012) and increase the potential for early warning and/or smart water management. However, advances in hydrologic DA research have not yet been adequately or timely implemented in operational forecast systems to improve the skill of forecasts for better informed real-world decision making. The objective of this work is to highlight the development of a generic linkage of the open source OpenDA package and the open source community hydrologic modeling framework Openstreams/WFLOW and its application in operational hydrological forecasting on various spatial scales. The coupling between OpenDA and Openstreams/wflow framework is based on the emerging standard Basic Model Interface (BMI) as advocated by CSDMS using cross-platform webservices (i.e. Apache Thrift) developed by Hut et al. (2016). The potential application of the OpenDA-WFLOW for operational hydrologic forecasting including its integration with Delft-FEWS (used by more than 40 operational forecast centers around the world (Werner et al., 2013)) is demonstrated by the presented case studies. We will also highlight the possibility to give real-time insight into the working of the DA methods applied for supporting the forecaster as mentioned as one of the burning issues by Liu et al., (2012).

Nucleotide sequence and phylogenetic analysis of Cucurbit yellow stunting disorder virus RNA 2.

PubMed

Livieratos, Ioannis C; Coutts, Robert H A

2002-06-01

The complete nucleotide sequence of Cucurbit yellow stunting disorder virus (CYSDV) RNA 2, a whitefly (Bemisia tabaci)-transmitted closterovirus with a bi-partite genome, is reported. CYSDV RNA 2 is 7,281 nucleotides long and contains the closterovirus hallmark gene array with a similar arrangement to the prototype member of the genus Crinivirus, Lettuce infectious yellows virus (LIYV). CYSDV RNA 2 contains open reading frames (ORFs) potentially encoding in a 5' to 3' direction for proteins of 5 kDa (ORF 1; hydrophobic protein), 62 kDa (ORF 2; heat shock protein 70 homolog, HSP70h), 59 kDa (ORF 3; protein of unknown function), 9 kDa (ORF 4; protein of unknown function), 28.5 kDa (ORF 5; coat protein, CP), 53 kDa (ORF 6; coat protein minor, CPm), and 26.5 kDa (ORF 7; protein of unknown function). Pairwise comparisons of CYSDV RNA 2-encoded proteins (HSP70h, p59 and CPm) among the closteroviruses showed that CYSDV is closely related to LIYV. Phylogenetic analysis based on the amino acid sequence of the HSP70h, indicated that CYSDV clusters with other members of the genus Crinivirus, and it is related to Little cherry virus-1 (LChV-1), but is distinct from the aphid- or mealybug-transmitted closteroviruses.

Nicotine- and methamphetamine-induced dopamine release evaluated with in-vivo binding of radiolabelled raclopride to dopamine D2 receptors: comparison with in-vivo microdialysis data.

PubMed

Kim, Sang Eun; Han, Seung-Moo

2009-07-01

The effect of substances which alter extracellular dopamine (DA) concentration has been studied by measuring changes in the binding of radiolabelled raclopride, a DA D2 receptor ligand that is sensitive to endogenous DA. To better characterize the relationship between extracellular DA concentration and DA D2 receptor binding of raclopride, we compared the changes of extracellular DA concentration (measured using in-vivo microdialysis) and in-vivo [3H]raclopride binding induced by different doses of methamphetamine (Meth) and nicotine, drugs that enhance DA release with and without blocking DA transporters (DATs), respectively, in rat striatum. Nicotine elicited a modest increase of striatal extrasynaptic extracellular DA, while Meth produced a marked increase of striatal extrasynaptic DA in a dose-dependent manner. There was a close correlation between the decrease in [3H]raclopride in-vivo binding and the increase in extrasynaptic DA concentration induced by both nicotine (r2=0.95, p<0.001) and Meth (r2=0.98, p=0.001), supporting the usefulness of the radiolabelled raclopride-binding measurement for the non-invasive assessment of DA release following interventions in the living brain. However, the linear regression analysis revealed that the ratio of percent DA increase to percent [3H]raclopride binding reduction was 25-fold higher for Meth (34.8:1) than for nicotine (1.4:1). The apparent discrepancy in the extrasynaptic DA-[3H]raclopride binding relationship between the DA-enhancing drugs with and without DAT-blocking property indicates that the competition between endogenous DA and radiolabelled raclopride takes place at the intrasynaptic rather than extrasynaptic DA D2 receptors and reflects synaptic concentration of DA.

Environmentally friendly, one-pot synthesis of folic acid-decorated graphene oxide-based drug delivery system

NASA Astrophysics Data System (ADS)

Lin, Quankui; Huang, Xiaojie; Tang, Junmei; Han, Yuemei; Chen, Hao

2013-12-01

A targeted drug delivery system based on graphene oxide (GO) was produced via one-pot synthesis method, taking advantages of the self-polymerization of the dopamine (DA). The polymerization of dopamine resulted in polydopamine capped GO nanocomposite. Meanwhile, the anti-tumor drug doxorubicin (DOX) can be loaded in the nanocomposite and the tumor cell targeting molecule folic acid (FA) can also been immobilized on the nanocomposite surface simultaneously. The size of the obtained FA-decorated GO-based drug delivery system (DA/GO(DOX)-FA) is about 600 nm. It renders a sustained drug release manner. The cell culture results reveal that the FA-decorated GO-based drug delivery system (DA/GO(DOX)-FA) via one-pot method shows property of targeted killing of cancer cells in vitro. This one-pot method just needs the pH adjusting to induce the self-polymerization of DA, but excludes the fussy chemical grafting process and the organic solvents, which make it an environmentally friendly method to synthesize FA-decorated GO-based drug delivery system.

Does transition from the da Vinci Si to Xi robotic platform impact single-docking technique for robot-assisted laparoscopic nephroureterectomy?

PubMed

Patel, Manish N; Aboumohamed, Ahmed; Hemal, Ashok

2015-12-01

To describe our robot-assisted nephroureterectomy (RNU) technique for benign indications and RNU with en bloc excision of bladder cuff (BCE) and lymphadenectomy (LND) for malignant indications using the da Vinci Si and da Vinci Xi robotic platform, with its pros and cons. The port placement described for Si can be used for standard and S robotic systems. This is the first report in the literature on the use of the da Vinci Xi robotic platform for RNU. After a substantial experience of RNU using different da Vinci robots from the standard to the Si platform in a single-docking fashion for benign and malignant conditions, we started using the newly released da Vinci Xi robot since 2014. The most important differences are in port placement and effective use of the features of da Vinci Xi robot while performing simultaneous upper and lower tract surgery. Patient positioning, port placement, step-by-step technique of single docking RNU-LND-BCE using the da Vinci Si and da Vinci Xi robot are shown in an accompanying video with the goal that centres using either robotic system benefit from the hints and tips. The first segment of video describes RNU-LND-BCE using the da Vinci Si followed by the da Vinci Xi to highlight differences. There was no need for patient repositioning or robot re-docking with the new da Vinci Xi robotic platform. We have experience of using different robotic systems for single docking RNU in 70 cases for benign (15) and malignant (55) conditions. The da Vinci Xi robotic platform helps operating room personnel in its easy movement, allows easier patient side-docking with the help of its boom feature, in addition to easy and swift movements of the robotic arms. The patient clearance feature can be used to avoid collision with the robotic arms or the patient's body. In patients with challenging body habitus and in situations where bladder cuff management is difficult, modifications can be made through reassigning the camera to a different port with utilisation of the retargeting feature of the da Vinci Xi when working on the bladder cuff or in the pelvis. The vision of the camera used for da Vinci Xi was initially felt to be inferior to that of the da Vinci Si; however, with a subsequent software upgrade this was much improved. The base of the da Vinci Xi is bigger, which does not slide and occasionally requires a change in table placement/operating room setup, and requires side-docking especially when dealing with very tall and obese patients for pelvic surgery. RNU alone or with LND-BCE is a challenging surgical procedure that addresses the upper and lower urinary tract simultaneously. Single docking and single robotic port placement for RNU-LND-BCE has evolved with the development of different generations of the robotic system. These procedures can be performed safely and effectively using the da Vinci S, Si or Xi robotic platform. The new da Vinci Xi robotic platform is more user-friendly, has easy installation, and is intuitive for surgeons using its features. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Nonlinear phase noise tolerance for coherent optical systems using soft-decision-aided ML carrier phase estimation enhanced with constellation partitioning

NASA Astrophysics Data System (ADS)

Li, Yan; Wu, Mingwei; Du, Xinwei; Xu, Zhuoran; Gurusamy, Mohan; Yu, Changyuan; Kam, Pooi-Yuen

2018-02-01

A novel soft-decision-aided maximum likelihood (SDA-ML) carrier phase estimation method and its simplified version, the decision-aided and soft-decision-aided maximum likelihood (DA-SDA-ML) methods are tested in a nonlinear phase noise-dominant channel. The numerical performance results show that both the SDA-ML and DA-SDA-ML methods outperform the conventional DA-ML in systems with constant-amplitude modulation formats. In addition, modified algorithms based on constellation partitioning are proposed. With partitioning, the modified SDA-ML and DA-SDA-ML are shown to be useful for compensating the nonlinear phase noise in multi-level modulation systems.

Beyond Donor-Acceptor (D-A) Approach: Structure-Optoelectronic Properties-Organic Photovoltaic Performance Correlation in New D-A1 -D-A2 Low-Bandgap Conjugated Polymers.

PubMed

Chochos, Christos L; Drakopoulou, Sofia; Katsouras, Athanasios; Squeo, Benedetta M; Sprau, Christian; Colsmann, Alexander; Gregoriou, Vasilis G; Cando, Alex-Palma; Allard, Sybille; Scherf, Ullrich; Gasparini, Nicola; Kazerouni, Negar; Ameri, Tayebeh; Brabec, Christoph J; Avgeropoulos, Apostolos

2017-04-01

Low-bandgap near-infrared polymers are usually synthesized using the common donor-acceptor (D-A) approach. However, recently polymer chemists are introducing more complex chemical concepts for better fine tuning of their optoelectronic properties. Usually these studies are limited to one or two polymer examples in each case study so far, though. In this study, the dependence of optoelectronic and macroscopic (device performance) properties in a series of six new D-A 1 -D-A 2 low bandgap semiconducting polymers is reported for the first time. Correlation between the chemical structure of single-component polymer films and their optoelectronic properties has been achieved in terms of absorption maxima, optical bandgap, ionization potential, and electron affinity. Preliminary organic photovoltaic results based on blends of the D-A 1 -D-A 2 polymers as the electron donor mixed with the fullerene derivative [6,6]-phenyl-C 71 -butyric acid methyl ester demonstrate power conversion efficiencies close to 4% with short-circuit current densities (J sc ) of around 11 mA cm -2 , high fill factors up to 0.70, and high open-circuit voltages (V oc s) of 0.70 V. All the devices are fabricated in an inverted architecture with the photoactive layer processed in air with doctor blade technique, showing the compatibility with roll-to-roll large-scale manufacturing processes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of atomoxetine on hyperactivity in an animal model of attention-deficit/hyperactivity disorder (ADHD).

PubMed

Moon, Su Jin; Kim, Chang Ju; Lee, Yeon Jung; Hong, Minha; Han, Juhee; Bahn, Geon Ho

2014-01-01

Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD). To investigate the therapeutic effects of atomoxetine on the motor activity in relation to the expression of the dopamine (DA) D2 receptor based on the hypothesis that DA system hypofunction causes ADHD symptoms, which would correlate with extensive D2 receptor overproduction and a lack of DA synthesis in specific brain regions: prefrontal cortex (PFC), striatum, and hypothalamus. Young male spontaneously hypertensive rats (SHR), animal models of ADHD, were randomly divided into four groups according to the daily dosage of atomoxetine and treated for 21 consecutive days. The animals were assessed using an open-field test, and the DA D2 receptor expression was examined. The motor activity improved continuously in the group treated with atomoxetine at a dose of 1 mg/Kg/day than in the groups treated with atomoxetine at a dose of 0.25 mg/Kg/day or 0.5 mg/Kg/day. With respect to DA D2 receptor immunohistochemistry, we observed significantly increased DA D2 receptor expression in the PFC, striatum, and hypothalamus of the SHRs as compared to the WKY rats. Treatment with atomoxetine significantly decreased DA D2 expression in the PFC, striatum, and hypothalamus of the SHRs, in a dose-dependent manner. Hyperactivity in young SHRs can be improved by treatment with atomoxetine via the DA D2 pathway.

Effect of Atomoxetine on Hyperactivity in an Animal Model of Attention-Deficit/Hyperactivity Disorder (ADHD)

PubMed Central

Moon, Su Jin; Kim, Chang Ju; Lee, Yeon Jung; Hong, Minha; Han, Juhee; Bahn, Geon Ho

2014-01-01

Background Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD). Purpose To investigate the therapeutic effects of atomoxetine on the motor activity in relation to the expression of the dopamine (DA) D2 receptor based on the hypothesis that DA system hypofunction causes ADHD symptoms, which would correlate with extensive D2 receptor overproduction and a lack of DA synthesis in specific brain regions: prefrontal cortex (PFC), striatum, and hypothalamus. Methods Young male spontaneously hypertensive rats (SHR), animal models of ADHD, were randomly divided into four groups according to the daily dosage of atomoxetine and treated for 21 consecutive days. The animals were assessed using an open-field test, and the DA D2 receptor expression was examined. Results The motor activity improved continuously in the group treated with atomoxetine at a dose of 1 mg/Kg/day than in the groups treated with atomoxetine at a dose of 0.25 mg/Kg/day or 0.5 mg/Kg/day. With respect to DA D2 receptor immunohistochemistry, we observed significantly increased DA D2 receptor expression in the PFC, striatum, and hypothalamus of the SHRs as compared to the WKY rats. Treatment with atomoxetine significantly decreased DA D2 expression in the PFC, striatum, and hypothalamus of the SHRs, in a dose-dependent manner. Conclusion Hyperactivity in young SHRs can be improved by treatment with atomoxetine via the DA D2 pathway. PMID:25271814

Development and evaluation of a decision aid for patients considering first‐line chemotherapy for metastatic breast cancer

PubMed Central

Chiew, Kimberly S.; Shepherd, Heather; Vardy, Janette; Tattersall, Martin H.N.; Butow, Phyllis N.; Leighl, Natasha B.

2007-01-01

Abstract Objective  Treatment decisions in advanced breast cancer are complex, with enhanced quality of life and survival among important treatment goals. Patients with metastatic breast cancer face the decision of whether or not to have chemotherapy, and many wish to be involved in this decision. We report the development and evaluation of a decision aid (DA) designed to assist patients facing this treatment decision. Design and sample  Women with metastatic breast cancer (n = 17) and medical oncologists in Australia and Canada (n = 7) were invited to evaluate the DA. Intervention  A DA was developed for patients with hormone‐resistant metastatic breast cancer considering chemotherapy. The DA presented options of supportive care, with or without chemotherapy. Potential benefits and side effects of different chemotherapy regimens, and evidence‐based prognostic estimates were described, and a values clarification exercise included. Main outcome measures  Patient questionnaires evaluating information and decision involvement preferences, attitudes toward the DA and oncologist feedback regarding attitudes toward the DA. Results  Seventeen patients participated; fifteen desired as much information about their illness as possible; sixteen wished to be actively involved in the decision‐making process. The majority rated the DA as highly acceptable, clear and informative, and would recommend it to others facing this treatment decision. Conclusion  This is the first DA for patients with advanced metastatic breast cancer considering chemotherapy. A randomized trial is underway to evaluate its role in clinical decision‐making. PMID:18297781

[Atomic absorption fingerprint and identification studies of Da Huo Luo pill. I. Exploration of inorganic elements fingerprint for establishment of industrial standard].

PubMed

Zhang, Qi-Feng; Zhu, Long-Yin; Ding, Shu-Liang; Wang, Chen; Tu, Long-Fei

2008-03-01

The fingerprints for most of Chinese medicines based on their organic compositions have been well established. Nevertheless, there are very few known fingerprints which are based on inorganic elements. In order to identify the Da Huo Luo Dan and its efficiency from other Chinese medicines, the authors attempted to set up a fingerprint which could be determined by the measurement of inorganic elements in Da Huo Luo Dan and other Chinese medicines. In the present study, the authors first employed 28 batches of Da Huo Luo Dan produced by Zhang-Shu Pharmatheutical Company in Jiang Xi Province to screen 12 kinds of inorganic elements measured by atomic absorption spectrophotometer and established the atomic absorption fingerprints. Secondly, the authors tried to identify Da Huo Luo Dan and other Chinese medicines by using the similarly analysis of vectors and the statistical analysis of compositional data. The result showed that the methods the authors used here were predictable to tell the efficiency of Da Huo Luo Dan from others. The authors' study also proves that establishment of standard for quality control by analysis of inorganic elements in Chinese medicines is feasible. The present study provides a new idea and a new technique that serve for the establishment of industrial standards for analysis of inorganic elements fingerprint to explore the effects of Chinese medicines.

Fluorescence chemodosimeter for dopamine based on the inner filter effect of the in situ generation of silver nanoparticles and fluorescent dye

NASA Astrophysics Data System (ADS)

Uppa, Yuwapon; Ngamdee, Kessarin; Promarak, Vinich; Ngeontae, Wittaya

2018-07-01

A new strategy for the sensitive and selective detection of dopamine (DA) was proposed. The chemodosimeter design was based on the measurement of the fluorescent quenching of fluorescein dye caused by the in situ generation of silver nanoparticles (AgNPs). The AgNPs can be simply generated by a reaction between DA and Ag+ in the presence of polymethacrylic acid (PMAA). In addition, the generated AgNPs possess the maximum surface plasmon resonance (SPR) at 440 nm and an increase in the SPR intensity with an increasing DA concentration. Basically, fluorescein dye can emit the fluorescent intensity maximum at 513 nm with excitation at 487 nm. Thus, fluorescent quenching was achieved due to an inner filter effect from the overlap between the excitation spectrum of the fluorescein dye and the SPR spectrum of the generated AgNPs. The degree of fluorescent quenching linearly depends on the number of generated AgNPs that can be directly related to the concentration of DA. The proposed chemodosimeter can be used to detect DA in a working linear concentration range of 1.0-5.0 μM at a detection limit of 10.6 nM. This chemodosimeter was successfully applied to determine DA in a real urine sample and a dopamine injection formulation with satisfactory results.

Sarcoplasmic calcium-binding protein: identification as a new allergen of the black tiger shrimp Penaeus monodon.

PubMed

Shiomi, Kazuo; Sato, Yuichiro; Hamamoto, Shohei; Mita, Hajime; Shimakura, Kuniyoshi

2008-01-01

Tropomyosin and arginine kinase have been identified as crustacean allergens. During purification of arginine kinase from black tiger shrimp Penaeus monodon, we found a new allergen of 20-kDa. A 20-kDa allergen was purified from the abdominal muscle of black tiger shrimp by salting-out, anion-exchange HPLC and reverse-phase HPLC. Following digestion of the 20-kDa allergen with lysyl endopeptidase, peptide fragments were isolated by reverse-phase HPLC, and 2 of them were sequenced. The 20-kDa allergen, together with tropomyosin and arginine kinase purified from black tiger shrimp, was evaluated for IgE reactivity by ELISA. Five species of crustaceans (kuruma shrimp, American lobster, pink shrimp, king crab and snow crab) were surveyed for the 20-kDa allergen by immunoblotting. The 20-kDa allergen was purified from black tiger shrimp and identified as a sarcoplasmic calcium-binding protein (SCP) based on the determined amino acid sequences of 2 enzymatic fragments. Of 16 sera from crustacean-allergic patients, 8 and 13 reacted to SCP and tropomyosin, respectively; the reactivity to arginine kinase was weakly recognized with 10 sera. In immunoblotting, an IgE-reactive 20-kDa protein was also detected in kuruma shrimp, American lobster and pink shrimp but not in 2 species of crab. Preadsorption of the sera with black tiger shrimp SCP abolished the IgE reactivity of the 20-kDa protein, suggesting the 20-kDa protein to be an SCP. SCP is a new crustacean allergen, and distribution of IgE-reactive SCP is probably limited to shrimp and crayfish. (c) 2008 S. Karger AG, Basel.

32 CFR 536.28 - Claims acknowledgment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... submission jurisdictionally deficient based on the requirements discussed in DA Pam 27-162, paragraphs 2-5... (HIPAA), 42 U.S.C. 1320d-1320d-8. See the parallel discussion at DA Pam 27-162, paragraph 2-7. ...

A microchip-based flow injection-amperometry system with mercaptopropionic acid modified electroless gold microelectrode for the selective determination of dopamine.

PubMed

Wang, Yi; Luo, Jie; Chen, Hengwu; He, Qiaohong; Gan, Nin; Li, Tianhua

2008-09-12

A novel chip-based flow injection analysis (FIA) system has been developed for automatic, rapid and selective determination of dopamine (DA) in the presence of ascorbic acid (AA). The system is composed of a polycarbonate (PC) microfluidic chip with an electrochemical detector (ED), a gravity pump, and an automatic sample loading and injection unit. The selectivity of the ED was improved by modification of the gold working microelectrode, which was fabricated on the PC chip by UV-directed electroless gold plating, with a self-assembled monolayer (SAM) of 3-mercaptopropionic acid (MPA). Postplating treatment methods for cleaning the surface of electroless gold microelectrodes were investigated to ensure the formation of high quality SAMs. The effects of detection potential, flow rate, and sampling volume on the performance of the chip-based FIA system were studied. Under optimum conditions, a detection limit of 74 nmol L(-1) for DA was achieved at the sample throughput rate of 180 h(-1). A RSD of 0.9% for peak heights was observed for 19 runs of a 100 micromol L(-1) DA solution. Interference-free determination of DA could be conducted if the concentration ratio of AA-DA was no more than 10.

Dopamine depletion shifts behavior from activity based reinforcers to more sedentary ones and adenosine receptor antagonism reverses that shift: Relation to ventral striatum DARPP32 phosphorylation patterns.

PubMed

López-Cruz, Laura; San Miguel, Noemí; Carratalá-Ros, Carla; Monferrer, Lidón; Salamone, John D; Correa, Mercè

2018-02-02

The mesolimbic dopamine (DA) system plays a critical role in behavioral activation and effort-based decision-making. DA depletion produces anergia (shifts to low effort options) in animals tested on effort-based decision-making tasks. Caffeine, the most consumed stimulant in the world, acts as an adenosine A 1 /A 2A receptor antagonist, and in striatal areas DA D 1 and D 2 receptors are co-localized with adenosine A 1 and A 2A receptors respectively. In the present work, we evaluated the effect of caffeine on anergia induced by the VMAT-2 inhibitor tetrabenazine (TBZ), which depletes DA. Anergia was evaluated in a three-chamber T-maze task in which animals can chose between running on a wheel (RW) vs. sedentary activities such as consuming sucrose or sniffing a neutral odor. TBZ-caffeine interactions in ventral striatum were evaluated using DARPP-32 phosphorylation patterns as an intracellular marker of DA-adenosine receptor interaction. In the T-maze, control mice spent more time running and much less consuming sucrose or sniffing. TBZ (4.0 mg/kg) reduced ventral striatal DA tissue levels as measured by HPLC, and also shifted preferences in the T-maze, reducing selection of the reinforcer that involved vigorous activity (RW), but increasing consumption of a reinforcer that required little effort (sucrose), at doses that had no effect on independent measures of appetite or locomotion in a RW. Caffeine at doses that had no effect on their own reversed the effects of TBZ on T-maze performance, and also suppressed TBZ-induced pDARPP-32(Thr34) expression as measured by western blot, suggesting a role for D 2 -A 2A interactions. These results support the idea that DA depletion produces anergia, but does not affect the primary motivational effects of sucrose. Caffeine, possibly by acting on A 2A receptors in ventral striatum, reversed the DA depletion effects. It is possible that caffeine, like selective adenosine A2A antagonists, could have some therapeutic benefit for treating effort-related symptoms. Copyright © 2018. Published by Elsevier Ltd.

Age-related changes in dopamine signaling in Nurr1 deficient mice as a model of Parkinson’s disease

PubMed Central

Zhang, Lifen; Le, Weidong; Xie, Wenjie; Dani, John A.

2011-01-01

The nuclear receptor related 1 (Nurr1) transcription factor contributes to the development and maintenance of dopamine (DA) neurons in the brain. We found that heterozygous Nurr1 knock-out (Nurr1 +/−) influenced the age-dependent decline in the number of DA neurons and influenced DA signaling. We examined the DA marker, tyrosine hydroxylase, using immunohistochemistry, and we measured DA signaling using fast-scan cyclic voltammetry in 3 age groups of wild-type (Nurr1 +/+) and mutant (Nurr1 +/−) mice: 3–6, 9–12, and 15–23 months old. Prior to significant loss of DA neurons and to the onset of parkinsonian symptoms, young Nurr1 +/− mice (3–6 months) exhibited a decrease in peak evoked DA release that was partially countered by a decrease in the rate of DA reuptake. As peak evoked DA release declined with age for both the wild-type and Nurr1 +/− mice, both genotypes manifested decreased DA reuptake. As the DA release fell further with age, decreased DA reuptake eventually could not adequately compensate the Nurr1 +/− mice. The results indicated that Nurr1 deficiency led to impaired DA release even before significant DA neuron loss. PMID:21531044

Colloid characterization and in situ release in shallow groundwater under different hydrogeology conditions.

PubMed

Zhou, Jingjing; Liu, Dan; Zhang, Wenjing; Chen, Xuequn; Huan, Ying; Yu, Xipeng

2017-06-01

Changes to groundwater hydrodynamics and chemistry can lead to colloid release that can have a major impact on the groundwater environment. To analyze the effects of colloid release caused by artificial groundwater recharge, field and laboratory tests on colloid characterization and colloid release were conducted. The field tests were carried out at an artificial recharge test site in Shandong Province. In the field investigation, one recharge water sample and five groundwater samples were collected and filtered through three levels of ultrafiltration membranes, with pore sizes of 0.45 μm, 100 kDa, and 50 kDa. The field results indicated that the colloid mass concentrations in groundwater retained between membranes with pore sizes of 100 kDa-0.45 μm and 50 kDa-100 kDa were 19 and 62 mg/L, respectively. In recharge water, the colloid mass concentrations retained by 100-kDa-0.45-μm and 50-kDa-100-kDa membranes were 3 and 99 mg/L, respectively. Colloids detected on the ultrafiltration membranes were mainly inorganic between 100 kDa and 0.45 μm, and mainly organic between 50 and 100 kDa. Based on the field colloid investigation results, the organic colloid was chosen in the laboratory experiments to reveal its release behavior under different conditions. Porous media diameter, flux, ionic strength (IS), and ion valence were changed to determine their influences on organic colloid concentration outflow from undisturbed porous media. The experiment's results indicate that decreasing the diameter, and increasing the flux, ionic strength, and the number of divalent cations, can promote organic colloid release. The organic colloid release rate in the early stage was high and is thus likely to affect the quality of groundwater. The results provide a useful scientific basis for minimizing changes to hydrodynamic and hydrochemical conditions during artificial recharge, thus safeguarding groundwater quality.

Towards guided data assimilation for operational hydrologic forecasting in the US Tennessee River basin

NASA Astrophysics Data System (ADS)

Weerts, A.; Wood, A. W.; Clark, M. P.; Carney, S.; Day, G. N.; Lemans, M.; Sumihar, J.; Newman, A. J.

2014-12-01

In the US, the forecasting approach used by the NWS River Forecast Centers and other regional organizations such as the Bonneville Power Administration (BPA) or Tennessee Valley Authority (TVA) has traditionally involved manual model input and state modifications made by forecasters in real-time. This process is time consuming and requires expert knowledge and experience. The benefits of automated data assimilation (DA) as a strategy for avoiding manual modification approaches have been demonstrated in research studies (eg. Seo et al., 2009). This study explores the usage of various ensemble DA algorithms within the operational platform used by TVA. The final goal is to identify a DA algorithm that will guide the manual modification process used by TVA forecasters and realize considerable time gains (without loss of quality or even enhance the quality) within the forecast process. We evaluate the usability of various popular algorithms for DA that have been applied on a limited basis for operational hydrology. To this end, Delft-FEWS was wrapped (via piwebservice) in OpenDA to enable execution of FEWS workflows (and the chained models within these workflows, including SACSMA, UNITHG and LAGK) in a DA framework. Within OpenDA, several filter methods are available. We considered 4 algorithms: particle filter (RRF), Ensemble Kalman Filter and Asynchronous Ensemble Kalman and Particle filter. Retrospective simulation results for one location and algorithm (AEnKF) are illustrated in Figure 1. The initial results are promising. We will present verification results for these methods (and possible more) for a variety of sub basins in the Tennessee River basin. Finally, we will offer recommendations for guided DA based on our results. References Seo, D.-J., L. Cajina, R. Corby and T. Howieson, 2009: Automatic State Updating for Operational Streamflow Forecasting via Variational Data Assimilation, 367, Journal of Hydrology, 255-275. Figure 1. Retrospectively simulated streamflow for the headwater basin above Powell River at Jonesville (red is observed flow, blue is simulated flow without DA, black is simulated flow with DA)

Nursing team's conceptions about the families of hospitalized children.

PubMed

Macedo, Isabela Fornerolli de; Souza, Tania Vignuda de; Oliveira, Isabel Cristina Dos Santos; Cibreiros, Sylvia Alves; Morais, Rita de Cássia Melão de; Vieira, Rosana Fidelis Coelho

2017-01-01

to describe nursing team care and discuss the nursing team's conception of companion families of hospitalized children. The study was based on the theoretical framework of Collière's theory of nursing care identity. this was a qualitative study with 14 members of a nursing team, conducted through an unstructured group interview. Thematic data analysis was employed. habitual and repair care was delegated to families, regardless of the child's clinical condition. the team's official discourse about the families of hospitalized children, as recommended by the literature, refers to the family's alterity and participation in care provision, with sights on discharge and defending family participation as beneficial to children. In practice, however, the nursing staff makes concessions about the presence of chaperoning families and delegates care. descrever os cuidados da equipe de enfermagem e discutir as concepções da equipe de enfermagem frente à família acompanhante da criança hospitalizada. O referencial teórico está vinculado à identidade do cuidado de enfermagem de Collière. Estudo qualitativo com quatorze membros da equipe de enfermagem, utilizando a técnica de entrevista não diretiva em grupo. Foi realizada análise temática dos dados. os cuidados habituais e de reparação prestados à criança estão sendo delegados à família, independentemente da situação clínica da criança. o discurso oficial da equipe de enfermagem frente à família acompanhante da criança hospitalizada, preconizado pela literatura, refere-se à alteridade e à participação da família nos cuidados à criança, prevendo sua alta e justificando a participação como benéfica para a criança. Em contrapartida, na prática, a enfermagem faz concessões sobre a permanência da família e delega os cuidados.

Comparing Real-time Versus Delayed Video Assessments for Evaluating ACGME Sub-competency Milestones in Simulated Patient Care Environments

PubMed Central

Stiegler, Marjorie; Hobbs, Gene; Martinelli, Susan M; Zvara, David; Arora, Harendra; Chen, Fei

2018-01-01

Background Simulation is an effective method for creating objective summative assessments of resident trainees. Real-time assessment (RTA) in simulated patient care environments is logistically challenging, especially when evaluating a large group of residents in multiple simulation scenarios. To date, there is very little data comparing RTA with delayed (hours, days, or weeks later) video-based assessment (DA) for simulation-based assessments of Accreditation Council for Graduate Medical Education (ACGME) sub-competency milestones. We hypothesized that sub-competency milestone evaluation scores obtained from DA, via audio-video recordings, are equivalent to the scores obtained from RTA. Methods Forty-one anesthesiology residents were evaluated in three separate simulated scenarios, representing different ACGME sub-competency milestones. All scenarios had one faculty member perform RTA and two additional faculty members perform DA. Subsequently, the scores generated by RTA were compared with the average scores generated by DA. Variance component analysis was conducted to assess the amount of variation in scores attributable to residents and raters. Results Paired t-tests showed no significant difference in scores between RTA and averaged DA for all cases. Cases 1, 2, and 3 showed an intraclass correlation coefficient (ICC) of 0.67, 0.85, and 0.50 for agreement between RTA scores and averaged DA scores, respectively. Analysis of variance of the scores assigned by the three raters showed a small proportion of variance attributable to raters (4% to 15%). Conclusions The results demonstrate that video-based delayed assessment is as reliable as real-time assessment, as both assessment methods yielded comparable scores. Based on a department’s needs or logistical constraints, our findings support the use of either real-time or delayed video evaluation for assessing milestones in a simulated patient care environment. PMID:29736352

Autocorrelation descriptor improvements for QSAR: 2DA_Sign and 3DA_Sign

NASA Astrophysics Data System (ADS)

Sliwoski, Gregory; Mendenhall, Jeffrey; Meiler, Jens

2016-03-01

Quantitative structure-activity relationship (QSAR) is a branch of computer aided drug discovery that relates chemical structures to biological activity. Two well established and related QSAR descriptors are two- and three-dimensional autocorrelation (2DA and 3DA). These descriptors encode the relative position of atoms or atom properties by calculating the separation between atom pairs in terms of number of bonds (2DA) or Euclidean distance (3DA). The sums of all values computed for a given small molecule are collected in a histogram. Atom properties can be added with a coefficient that is the product of atom properties for each pair. This procedure can lead to information loss when signed atom properties are considered such as partial charge. For example, the product of two positive charges is indistinguishable from the product of two equivalent negative charges. In this paper, we present variations of 2DA and 3DA called 2DA_Sign and 3DA_Sign that avoid information loss by splitting unique sign pairs into individual histograms. We evaluate these variations with models trained on nine datasets spanning a range of drug target classes. Both 2DA_Sign and 3DA_Sign significantly increase model performance across all datasets when compared with traditional 2DA and 3DA. Lastly, we find that limiting 3DA_Sign to maximum atom pair distances of 6 Å instead of 12 Å further increases model performance, suggesting that conformational flexibility may hinder performance with longer 3DA descriptors. Consistent with this finding, limiting the number of bonds in 2DA_Sign from 11 to 5 fails to improve performance.

A phase IIa study of rhLTα-Da in combination with cisplatin and fluorouracil for patients with metastatic esophageal squamous cell carcinoma or gastric adenocarcinoma.

PubMed

Wang, Feng-Hua; Wang, Yun; Chen, Zhen-Dong; Chen, Jian-Hua; Qin, Feng-Zhan; Jiang, Wen-Qi; Li, Yu-Hong

2016-11-01

Recombinant human lymphotoxin-α derivative (rhLTα-Da) is a lymphotoxin-α derivative missing 27 N-terminal amino acid residues. This multicenter phase IIa trial was conducted to evaluate the safety, efficacy and pharmacokinetics of rhLTα-Da with cisplatin (DDP) and 5-fluorouracil (5-Fu) for metastatic esophageal squamous cell cancer (ESCC) and gastric adenocarcinoma (GC). Two different rhLTα-Da doses (10 µg/m 2 /d and 20 µg/m 2 /d) in combination with DDP and 5-Fu were evaluated in this study. The first 6 ESCC and 6 GC patients were given 10 µg/m 2 /d rhLTα-Da followed by DDP (15 mg/m 2 /d) and 5-Fu (750 mg/m 2 /d) on days 1-5. The next 6 ESCC and 6 GC patients were given 20 µg/m 2 /d rhLTα-Da after fewer than 2 of the 6 patients who received the 10 µg/m 2 /d dose exhibited dose-limiting rhLTα-Da-related toxicities. The treatment was 21 days a cycle until a maximum of 6. The rhLTα-Da pharmacokinetic analyses were performed. Twelve ESCC and 12 GC patients were enrolled. The toxicities were controllable and reversible. The most common adverse events related to rhLTα-Da were chills (37.5 %, 9/24) and fever (16.7 %, 4/24) (all grades 1-2). The overall response rates in the 10- and 20-µg/m 2 /d groups were 50 % (6/12) and 33.3 % (4/12), respectively, and the overall response rates of the ESCC and GC patients were 66.7 % (8/12) and 16.7 % (2/12), respectively. rhLTα-Da in combination with DDP and 5-Fu exhibited a tolerable toxicity profile. The addition of rhLTα-Da may enhance the anti-tumor efficacy of platinum-based chemotherapy in metastatic ESCC.

Data Administration at a Regional University: A Case Study.

ERIC Educational Resources Information Center

Gose, Frank J.

Data administration (DA) is a position that has emerged with the growth of information technologies. A review of DA literature confirms that, although DA is widely associated with database management systems (DBMS), there is no standard DA job description, DA staffing and location within the organization vary, and DA functions range in description…

From sanddabs to blue whales: the pervasiveness of domoic acid.

PubMed

Lefebvre, Kathi A; Bargu, Sibel; Kieckhefer, Tom; Silver, Mary W

2002-07-01

Domoic acid (DA) is a potent food web transferred algal toxin that has caused dramatic mortality events involving sea birds and sea lions. Although no confirmed DA toxicity events have been reported in whales, here we present data demonstrating that humpback and blue whales are exposed to the toxin and consume DA contaminated prey. Whale fecal samples were found to contain DA at levels ranging from 10 to 207microg DA g(-1) feces via HPLC-UV methods. SEM analysis of whale feces containing DA, collected from krill-feeding whales, revealed the presence of diatom frustules identified as Pseudo-nitzschia australis, a known DA producer. Humpback whales were observed feeding on anchovies and sardines that contained DA at levels ranging from 75 to 444microg DA g(-1) viscera. DA contamination of whale feces and fish occurred only during blooms of toxic Pseudo-nitzschia. Additionally, several novel fish species collected during a toxic diatom bloom were tested for DA. Fish as diverse as benthic sanddabs and pelagic albacore were found to contain the neurotoxin, suggesting that DA permeates benthic as well as pelagic communities.

Two forms of Vibrio cholerae O1 El Tor hemolysin derived from identical precursor protein.

PubMed

Ikigai, H; Ono, T; Nakae, T; Otsuru, H; Shimamura, T

1999-01-08

Vibrio cholerae O1 grown in heart infusion broth produces two forms of El Tor hemolysin (ETH) monomers of 65 and 50 kDa. These monomers form several different sizes of mixed oligomers ranging from 180 to 280 kDa in the liposomal membranes. We found that the N-terminal amino acid sequences, NH2-Trp-Pro-Ala-Pro-Ala-Asn-Ser-Glu, of both the 65- and 50-kDa toxins were identical. We assumed, therefore, that the 65- and 50-kDa toxins were derivatives of the identical precursor protein and the 50-kDa protein was a truncated derivative of 65-kDa ETH. To substantiate this assumption, we treated the 260-kDa oligomer with trypsin and obtained a 190-kDa oligomer. This 190-kDa oligomer consisted of only the 50-kDa subunits. Both 260- and 190-kDa oligomers formed ion channels indistinguishable from each other in planar lipid bilayers. These results suggest that the essential part of the ETH in forming the membrane-damaging aggregate is a 50-kDa protein.

Exploring "DIALANG'S" Diagnostic Feedback in Online L2 Dynamic Assessment

ERIC Educational Resources Information Center

Ebadi, Saman

2016-01-01

Dynamic assessment (DA) as an alternative to psychometric-based testing focuses on the collaborative dialogue between the learners and the mediator to move the learners from their current capabilities. This study represents a web-based qualitative inquiry in online DA which aims at addressing the inadequacy of the diagnostic feedback of the…

Microstructure design of titanate-based electroceramics =

NASA Astrophysics Data System (ADS)

Amaral, Luis Miguel de Almeida

Electrocerâmicos sao uma classe de materiais avancados com propriedades electricas valiosas para aplicacoes. Estas propriedades sao geralmente muito dependentes da microestrutura dos materiais. Portanto, o objectivo geral deste trabalho e investigar o desenho da resposta dielectrica de filmes espessos obtidos por Deposicao Electroforetica (EPD) e cerâmicos monoliticos, atraves do controlo da evolucao da microestrutura durante a sinterizacao de electrocerâmicos a base de titanatos. Aplicacoes sem fios na industria microelectronica e de comunicacoes, em rapido crescimento, tornaram-se um importante mercado para os fabricantes de semicondutores. Devido a constante necessidade de miniaturizacao, reducao de custos e maior funcionalidade e integracao, a tecnologia de filmes espessos esta a tornar-se uma abordagem de processamento de materiais funcionais cada vez mais importante. Uma tecnica adequada neste contexto e EPD. Os filmes espessos resultantes necessitam de um passo subsequente de sinterizacao que e afectada pelo substrato subjacente, tendo este um forte efeito sobre a evolucao da microestrutura. Relacionado com a miniaturizacao e a discriminacao do sinal, materiais dielectricos usados como componentes operando a frequencias das microondas em aplicacoes na industria microelectronica de comunicacoes devem apresentar baixas perdas dielectricas e elevadas permitividade dielectrica e estabilidade com a temperatura. Materiais do sistema BaO-Ln2O3- TiO2 (BLnT: Ln = La ou Nd), como BaLa4Ti4O15 (BLT) e Ba4.5Nd9Ti18O54 (BNT), cumprem esses requisitos e sao interessantes para aplicacoes, por exemplo, em estacoes de base para comunicacoes moveis ou em ressonadores para telefones moveis, onde a miniaturizacao dos dispositivos e muito importante. Por sua vez, o titanato de estroncio (SrTiO3, STO) e um ferroelectrico incipiente com constante dielectrica elevada e baixas perdas, que encontra aplicacao em, por exemplo, condensadores de camada interna, tirando partido de fronteiras de grao altamente resistivas. A dependencia da permitividade dielectrica do campo electrico aplicado torna este material muito interessante para aplicacoes em dispositivos de microondas sintonizaveis. Materiais a base de STO sao tambem interessantes para aplicacoes termoelectricas, que podem contribuir para a reducao da actual dependencia de combustiveis fosseis por meio da geracao de energia a partir de calor desaproveitado. No entanto, as mesmas fronteiras de grao resistivas sao um obstaculo relativamente a eficiencia do STO para aplicacoes termoelectricas. (Abstract shortened by ProQuest.).

Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study.

PubMed

Choi, Yoon Jin; Lee, Dong Ho; Choi, Myung Gyu; Lee, Sung Joon; Kim, Sung Kook; Song, Geun Am; Rhee, Poong Lyul; Jung, Hwoon Yong; Kang, Dae Hwan; Lee, Yong Chan; Lee, Si Hyung; Choi, Suck Chei; Shim, Ki Nam; Seol, Sang Yong; Moon, Jeong Seop; Shin, Yong Woon; Kim, Hyun Soo; Lee, Soo Teik; Cho, Jin Woong; Choi, Eun Kwang; Lee, Oh Young; Jang, Jin Seok

2017-11-01

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was -0.4% (95% confidence interval, -9.8% to 9.1%), which was above the non-inferiority margin of -14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670). © 2017 The Korean Academy of Medical Sciences.

Values clarification in a decision aid about fertility preservation: does it add to information provision?

PubMed Central

2014-01-01

Background We aimed to evaluate the effect of a decision aid (DA) with information only compared to a DA with values clarification exercise (VCE), and to study the role of personality and information seeking style in DA-use, decisional conflict (DC) and knowledge. Methods Two scenario-based experiments were conducted with two different groups of healthy female participants. Dependent measures were: DC, knowledge, and DA-use (time spent, pages viewed, VCE used). Respondents were randomized between a DA with information only (VCE-) and a DA with information plus a VCE(VCE+) (experiment 1), or between information only (VCE-), information plus VCE without referral to VCE(VCE+), and information plus a VCE with specific referral to the VCE, requesting participants to use the VCE(VCE++) (experiment 2). In experiment 2 we additionally measured personality (neuroticism/conscientiousness) and information seeking style (monitoring/blunting). Results Experiment 1. There were no differences in DC, knowledge or DA-use between VCE- (n=70) and VCE+ (n=70). Both DAs lead to a mean gain in knowledge from 39% at baseline to 73% after viewing the DA. Within VCE+, VCE-users (n=32, 46%) reported less DC compared to non-users. Since there was no difference in DC between VCE- and VCE+, this is likely an effect of VCE-use in a self-selected group, and not of the VCE per se. Experiment 2. There were no differences in DC or knowledge between VCE- (n=65), VCE+ (n=66), VCE++ (n=66). In all groups, knowledge increased on average from 42% at baseline to 72% after viewing the DA. Blunters viewed fewer DA-pages (R=0.38, p<.001). More neurotic women were less certain (R=0.18, p<.01) and felt less supported in decision making (R=0.15, p<.05); conscientious women felt more certain (R=-0.15, p<.05) and had more knowledge after viewing the DA (R=0.15, p<.05). Conclusions Both DAs lead to increased knowledge in healthy populations making hypothetical decisions, and use of the VCE did not improve knowledge or DC. Personality characteristics were associated to some extent with DA-use, information seeking styles with aspects of DC. More research is needed to make clear recommendations regarding the need for tailoring of information provision to personality characteristics, and to assess the effect of VCE use in actual patients. PMID:25106453

Parameterized source term in the diffusion approximation for enhanced near-field modeling of collimated light

NASA Astrophysics Data System (ADS)

Jia, Mengyu; Wang, Shuang; Chen, Xueying; Gao, Feng; Zhao, Huijuan

2016-03-01

Most analytical methods for describing light propagation in turbid medium exhibit low effectiveness in the near-field of a collimated source. Motivated by the Charge Simulation Method in electromagnetic theory as well as the established discrete source based modeling, we have reported on an improved explicit model, referred to as "Virtual Source" (VS) diffuse approximation (DA), to inherit the mathematical simplicity of the DA while considerably extend its validity in modeling the near-field photon migration in low-albedo medium. In this model, the collimated light in the standard DA is analogously approximated as multiple isotropic point sources (VS) distributed along the incident direction. For performance enhancement, a fitting procedure between the calculated and realistic reflectances is adopted in the nearfield to optimize the VS parameters (intensities and locations). To be practically applicable, an explicit 2VS-DA model is established based on close-form derivations of the VS parameters for the typical ranges of the optical parameters. The proposed VS-DA model is validated by comparing with the Monte Carlo simulations, and further introduced in the image reconstruction of the Laminar Optical Tomography system.

Three-Dimensional-Bioprinted Dopamine-Based Matrix for Promoting Neural Regeneration.

PubMed

Zhou, Xuan; Cui, Haitao; Nowicki, Margaret; Miao, Shida; Lee, Se-Jun; Masood, Fahed; Harris, Brent T; Zhang, Lijie Grace

2018-03-14

Central nerve repair and regeneration remain challenging problems worldwide, largely because of the extremely weak inherent regenerative capacity and accompanying fibrosis of native nerves. Inadequate solutions to the unmet needs for clinical therapeutics encourage the development of novel strategies to promote nerve regeneration. Recently, 3D bioprinting techniques, as one of a set of valuable tissue engineering technologies, have shown great promise toward fabricating complex and customizable artificial tissue scaffolds. Gelatin methacrylate (GelMA) possesses excellent biocompatible and biodegradable properties because it contains many arginine-glycine-aspartic acids (RGD) and matrix metalloproteinase sequences. Dopamine (DA), as an essential neurotransmitter, has proven effective in regulating neuronal development and enhancing neurite outgrowth. In this study, GelMA-DA neural scaffolds with hierarchical structures were 3D-fabricated using our custom-designed stereolithography-based printer. DA was functionalized on GelMA to synthesize a biocompatible printable ink (GelMA-DA) for improving neural differentiation. Additionally, neural stem cells (NSCs) were employed as the primary cell source for these scaffolds because of their ability to terminally differentiate into a variety of cell types including neurons, astrocytes, and oligodendrocytes. The resultant GelMA-DA scaffolds exhibited a highly porous and interconnected 3D environment, which is favorable for supporting NSC growth. Confocal microscopy analysis of neural differentiation demonstrated that a distinct neural network was formed on the GelMA-DA scaffolds. In particular, the most significant improvements were the enhanced neuron gene expression of TUJ1 and MAP2. Overall, our results demonstrated that 3D-printed customizable GelMA-DA scaffolds have a positive role in promoting neural differentiation, which is promising for advancing nerve repair and regeneration in the future.

Comparison of two simulation systems to support robotic-assisted surgical training: a pilot study (Swine model).

PubMed

Whitehurst, Sabrina V; Lockrow, Ernest G; Lendvay, Thomas S; Propst, Anthony M; Dunlow, Susan G; Rosemeyer, Christopher J; Gobern, Joseph M; White, Lee W; Skinner, Anna; Buller, Jerome L

2015-01-01

To compare the efficacy of simulation-based training between the Mimic dV- Trainer and traditional dry lab da Vinci robot training. A prospective randomized study analyzing the performance of 20 robotics-naive participants. Participants were enrolled in an online da Vinci Intuitive Surgical didactic training module, followed by training in use of the da Vinci standard surgical robot. Spatial ability tests were performed as well. Participants were randomly assigned to 1 of 2 training conditions: performance of 3 Fundamentals of Laparoscopic Surgery dry lab tasks using the da Vinci or performance of 4 dV-Trainer tasks. Participants in both groups performed all tasks to empirically establish proficiency criterion. Participants then performed the transfer task, a cystotomy closure using the daVinci robot on a live animal (swine) model. The performance of robotic tasks was blindly assessed by a panel of experienced surgeons using objective tracking data and using the validated Global Evaluative Assessment of Robotic Surgery (GEARS), a structured assessment tool. No statistically significant difference in surgeon performance was found between the 2 training conditions, dV-Trainer and da Vinci robot. Analysis of a 95% confidence interval for the difference in means (-0.803 to 0.543) indicated that the 2 methods are unlikely to differ to an extent that would be clinically meaningful. Based on the results of this study, a curriculum on the dV- Trainer was shown to be comparable to traditional da Vinci robot training. Therefore, we have identified that training on a virtual reality system may be an alternative to live animal training for future robotic surgeons. Published by Elsevier Inc.

Platelets contribute to postnatal occlusion of the ductus arteriosus.

PubMed

Echtler, Katrin; Stark, Konstantin; Lorenz, Michael; Kerstan, Sandra; Walch, Axel; Jennen, Luise; Rudelius, Martina; Seidl, Stefan; Kremmer, Elisabeth; Emambokus, Nikla R; von Bruehl, Marie-Luise; Frampton, Jon; Isermann, Berend; Genzel-Boroviczény, Orsolya; Schreiber, Christian; Mehilli, Julinda; Kastrati, Adnan; Schwaiger, Markus; Shivdasani, Ramesh A; Massberg, Steffen

2010-01-01

The ductus arteriosus (DA) is a fetal shunt vessel between the pulmonary artery and the aorta that closes promptly after birth. Failure of postnatal DA closure is a major cause of morbidity and mortality particularly in preterm neonates. The events leading to DA closure are incompletely understood. Here we show that platelets have an essential role in DA closure. Using intravital microscopy of neonatal mice, we observed that platelets are recruited to the luminal aspect of the DA during closure. DA closure is impaired in neonates with malfunctioning platelet adhesion or aggregation or with defective platelet biogenesis. Defective DA closure resulted in a left-to-right shunt with increased pulmonary perfusion, pulmonary vascular remodeling and right ventricular hypertrophy. Our findings indicate that platelets are crucial for DA closure by promoting thrombotic sealing of the constricted DA and by supporting luminal remodeling. A retrospective clinical study revealed that thrombocytopenia is an independent predictor for failure of DA closure in preterm human newborns, indicating that platelets are likely to contribute to DA closure in humans.

Evaluation of a Mammography Screening Decision Aid for Women Aged 75 and Older: Protocol for a Cluster-randomized Controlled Trial

PubMed Central

Schonberg, Mara A; Kistler, Christine E; Nekhlyudov, Larissa; Fagerlin, Angela; Davis, Roger B; Wee, Christina C; Marcantonio, Edward R; Lewis, Carmen L; Stanley, Whitney A; Crutchfield, Trisha M.; Hamel, Mary Beth

2015-01-01

Purpose There is insufficient evidence to recommend mammography for women >75 years. Guidelines recommend that older women be informed of the uncertainty of benefit and potential for harm, especially for women with short life expectancy. However, few older women are informed of harms of screening and many with short life expectancy are screened. Therefore, we aim to test whether a mammography screening decision aid (DA) for women >75 years affects their use of mammography, particularly for women with <10 year life expectancy. Methods/Design The DA is a self-administered pamphlet that includes information on screening outcomes, tailored information on breast cancer risk, health, life expectancy, and competing mortality risks, and includes a values clarification exercise. We are conducting a large cluster randomized controlled trial (RCT) of the DA with the primary care provider (PCP) as the unit of randomization to evaluate its efficacy. We plan to recruit 550 women 75-89 years from 100 PCPs to receive either the mammography DA or a pamphlet on home safety for older adults (control arm) before a visit with their PCP, depending on their PCP's randomization assignment. The primary outcome is receipt of mammography screening assessed through chart abstraction. Secondary outcomes include effect of the DA on older women's screening intentions, knowledge, and decisional conflict, and on documented discussions about mammography by their PCPs. We will recruit women from 5 Boston-based primary care practices (3 community-based internal medicine practices and 2 academic practices), and 2 North Carolina-based academic primary care practices. Discussion It is essential that we test the DA in a large RCT to determine if it is efficacious and to substantiate the need for broad translation into clinical practice. Our DA has the potential to improve health care utilization and care in a manner dictated by patient preferences. PMID:26229741

Modeling time-dependent corrosion fatigue crack propagation in 7000 series aluminum alloys

NASA Technical Reports Server (NTRS)

Mason, Mark E.; Gangloff, Richard P.

1994-01-01

Stress corrosion cracking and corrosion fatigue experiments were conducted with the susceptible S-L orientation of AA7075-T651, immersed in acidified and inhibited NaCl solution, to provide a basis for incorporating environmental effects into fatigue crack propagation life prediction codes such as NASA FLAGRO. This environment enhances da/dN by five to ten-fold compared to fatigue in moist air. Time-based crack growth rates from quasi-static load experiments are an order of magnitude too small for accurate linear superposition prediction of da/dN for loading frequencies above 0.001 Hz. Alternate methods of establishing da/dt, based on rising-load or ripple-load-enhanced crack tip strain rate, do not increase da/dt and do not improve linear superposition. Corrosion fatigue is characterized by two regimes of frequency dependence; da/dN is proportional to f(exp -1) below 0.001 Hz and to F(exp 0) to F(exp -0.1) for higher frequencies. Da/dN increases mildly both with increasing hold-time at K(sub max) and with increasing rise-time for a range of loading waveforms. The mild time-dependence is due to cycle-time-dependent corrosion fatigue growth. This behavior is identical for S-L nd L-T crack orientations. The frequency response of environmental fatigue in several 7000 series alloys is variable and depends on undefined compositional or microstructural variables. Speculative explanations are based on the effect of Mg on occluded crack chemistry and embritting hydrogen uptake, or on variable hydrogen diffusion in the crack tip process zone. Cracking in the 7075/NaCl system is adequately described for life prediction by linear superposition for prolonged load-cycle periods, and by a time-dependent upper bound relationship between da/dN and delta K for moderate loading times.

The coolest DA white dwarfs detected at soft X-ray wavelengths

NASA Technical Reports Server (NTRS)

Kidder, K. M.; Holberg, J. B.; Barstow, M. A.; Tweedy, R. W.; Wesemael, F.

1992-01-01

New soft X-ray/EUV photometric observations of the DA white dwarfs KPD 0631 + 1043 = WD 0631 + 107 and PG 1113 + 413 = WD 1113 + 413 are analyzed. Previously reported soft X-ray detections of three other DAs and the failure to detect a fourth DA in deep Exosat observations are investigated. New ground-based spectra are presented for all of the objects, with IUE Ly-alpha spectra for some. These data are used to constrain the effective temperatures and surface gravities. The improved estimates of these parameters are employed to refer a photospheric He abundance for the hotter objects and to elucidate an effective observational low-temperature threshold for the detection of pure hydrogen DA white dwarfs at soft X-ray wavelengths.

An integrative theory of the phasic and tonic modes of dopamine modulation in the prefrontal cortex.

PubMed

Dreher, Jean-Claude; Burnod, Yves

2002-01-01

This paper presents a model of both tonic and phasic dopamine (DA) effects on maintenance of working memory representations in the prefrontal cortex (PFC). The central hypothesis is that DA modulates the efficacy of inputs to prefrontal pyramidal neurons to prevent interferences for active maintenance. Phasic DA release, due to DA neurons discharges, acts at a short time-scale (a few seconds), while the tonic mode of DA release, independent of DA neurons firing, acts at a long time-scale (a few minutes). The overall effect of DA modulation is modeled as a threshold restricting incoming inputs arriving on PFC neurons. Phasic DA release temporary increases this threshold while tonic DA release progressively increases the basal level of this threshold. Thus, unlike the previous gating theory of phasic DA release, proposing that it facilitates incoming inputs at the time of their arrival, the effect of phasic DA release is supposed to restrict incoming inputs during a period of time after DA neuron discharges. The model links the cellular and behavioral levels during performance of a working memory task. It allows us to understand why a critical range of DA D1 receptors stimulation is required for optimal working memory performance and how D1 receptor agonists (respectively antagonists) increase perseverations (respectively distractability). Finally, the model leads to several testable predictions, including that the PFC regulates DA neurons firing rate to adapt to the delay of the task and that increase in tonic DA release may either improve or decrease performance, depending on the level of DA receptors stimulation at the beginning of the task.

Optogenetic versus electrical stimulation of dopamine terminals in the nucleus accumbens reveals local modulation of presynaptic release

PubMed Central

Melchior, James R.; Ferris, Mark J.; Stuber, Garret D.; Riddle, David R.; Jones, Sara R.

2015-01-01

The nucleus accumbens is highly heterogeneous, integrating regionally distinct afferent projections and accumbal interneurons, resulting in diverse local microenvironments. Dopamine (DA) neuron terminals similarly express a heterogeneous collection of terminal receptors that modulate DA signaling. Cyclic voltammetry is often used to probe DA terminal dynamics in brain slice preparations; however, this method traditionally requires electrical stimulation to induce DA release. Electrical stimulation excites all of the neuronal processes in the stimulation field, potentially introducing simultaneous, multi-synaptic modulation of DA terminal release. We used optogenetics to selectively stimulate DA terminals and used voltammetry to compare DA responses from electrical and optical stimulation of the same area of tissue around a recording electrode. We found that with multiple pulse stimulation trains, optically stimulated DA release increasingly exceeded that of electrical stimulation. Furthermore, electrical stimulation produced inhibition of DA release across longer duration stimulations. The GABAB antagonist, CGP 55845, increased electrically stimulated DA release significantly more than light stimulated release. The nicotinic acetylcholine receptor antagonist, dihydro-β-erythroidine hydrobromide, inhibited single pulse electrically stimulated DA release while having no effect on optically stimulated DA release. Our results demonstrate that electrical stimulation introduces local multi-synaptic modulation of DA release that is absent with optogenetically targeted stimulation. PMID:26011081

SAGES TAVAC safety and effectiveness analysis: da Vinci ® Surgical System (Intuitive Surgical, Sunnyvale, CA).

PubMed

Tsuda, Shawn; Oleynikov, Dmitry; Gould, Jon; Azagury, Dan; Sandler, Bryan; Hutter, Matthew; Ross, Sharona; Haas, Eric; Brody, Fred; Satava, Richard

2015-10-01

The da Vinci(®) Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) is a computer-assisted (robotic) surgical system designed to enable and enhance minimally invasive surgery. The Food and Drug Administration (FDA) has cleared computer-assisted surgical systems for use by trained physicians in an operating room environment for laparoscopic surgical procedures in general, cardiac, colorectal, gynecologic, head and neck, thoracic and urologic surgical procedures. There are substantial numbers of peer-reviewed papers regarding the da Vinci(®) Surgical System, and a thoughtful assessment of evidence framed by clinical opinion is warranted. The SAGES da Vinci(®) TAVAC sub-committee performed a literature review of the da Vinci(®) Surgical System regarding gastrointestinal surgery. Conclusions by the sub-committee were vetted by the SAGES TAVAC Committee and SAGES Executive Board. Following revisions, the document was evaluated by the TAVAC Committee and Executive Board again for final approval. Several conclusions were drawn based on expert opinion organized by safety, efficacy, and cost for robotic foregut, bariatric, hepatobiliary/pancreatic, colorectal surgery, and single-incision cholecystectomy. Gastrointestinal surgery with the da Vinci(®) Surgical System is safe and comparable, but not superior to standard laparoscopic approaches. Although clinically acceptable, its use may be costly for select gastrointestinal procedures. Current data are limited to the da Vinci(®) Surgical System; further analyses are needed.

The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons?

PubMed Central

Margolis, Elyssa B; Lock, Hagar; Hjelmstad, Gregory O; Fields, Howard L

2006-01-01

The ventral tegmental area (VTA) and in particular VTA dopamine (DA) neurons are postulated to play a central role in reward, motivation and drug addiction. However, most evidence implicating VTA DA neurons in these functions is based on indirect electrophysiological characterization, rather than cytochemical identification. These physiological criteria were first established in the substantia nigra pars compacta (SNc), but their validity in the VTA is uncertain. In the current study we found that while 88 ± 2% of SNc neurons labelled by the neuronal marker NeuN were co-labelled for the catecholamine enzyme tyrosine hydroxylase (TH), a much smaller percentage (55 ± 2%) of VTA neurons co-expressed TH. In addition, using in vitro whole-cell recordings we found that widely accepted physiological criteria for VTA DA neurons, including the hyperpolarization-activated inwardly rectifying non-specific cation current (Ih), spike duration, and inhibition by DA D2 receptor agonists, do not reliably predict the DA content of VTA neurons. We could not distinguish DA neurons from other VTA neurons by size, shape, input resistance, Ih size, or spontaneous firing rate. Although the absence of an Ih reliably predicted that a VTA neuron was non-dopaminergic, and Ih(−) neurons differ from Ih(+) neurons in firing rate, interspike interval (ISI) standard deviation, and ISI skew, no physiological property examined here is both sensitive and selective for DA neurons in the VTA. We conclude that reliable physiological criteria for VTA DA neuron identification have yet to be determined, and that the criteria currently being used are unreliable. PMID:16959856

Dopamine signaling and myopia development: What are the key challenges.

PubMed

Zhou, Xiangtian; Pardue, Machelle T; Iuvone, P Michael; Qu, Jia

2017-11-01

In the face of an "epidemic" increase in myopia over the last decades and myopia prevalence predicted to reach 2.5 billion people by the end of this decade, there is an urgent need to develop effective and safe therapeutic interventions to slow down this "myopia booming" and prevent myopia-related complications and vision loss. Dopamine (DA) is an important neurotransmitter in the retina and mediates diverse functions including retina development, visual signaling, and refractive development. Inspired by the convergence of epidemiological and animal studies in support of the inverse relationship between outdoor activity and risk of developing myopia and by the close biological relationship between light exposure and dopamine release/signaling, we felt it is timely and important to critically review the role of DA in myopia development. This review will revisit several key points of evidence for and against DA mediating light control of myopia: 1) the causal role of extracellular retinal DA levels, 2) the mechanism and action of dopamine D1 and D2 receptors and 3) the roles of cellular/circuit retinal pathways. We examine the experiments that show causation by altering DA, DA receptors and visual pathways using pharmacological, transgenic, or visual environment approaches. Furthermore, we critically evaluate the safety issues of a DA-based treatment strategy and some approaches to address these issues. The review identifies the key questions and challenges in translating basic knowledge on DA signaling and myopia from animal studies into effective pharmacological treatments for myopia in children. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity

USGS Publications Warehouse

Lefebvre, Kathi A.; Frame, Elizabeth R.; Gulland, Frances; Hansen, John D.; Kendrick, Preston S.; Beyer, Richard P.; Bammler, Theo K.; Farin, Frederico M.; Hiolski, Emma M.; Smith, Donald R.; Marcinek, David J.

2012-01-01

The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity.

PubMed

Lefebvre, Kathi A; Frame, Elizabeth R; Gulland, Frances; Hansen, John D; Kendrick, Preston S; Beyer, Richard P; Bammler, Theo K; Farin, Frederico M; Hiolski, Emma M; Smith, Donald R; Marcinek, David J

2012-01-01

The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits.

PubMed

Salamone, J D; Correa, M; Farrar, A; Mingote, S M

2007-04-01

Over the last several years, it has become apparent that there are critical problems with the hypothesis that brain dopamine (DA) systems, particularly in the nucleus accumbens, directly mediate the rewarding or primary motivational characteristics of natural stimuli such as food. Hypotheses related to DA function are undergoing a substantial restructuring, such that the classic emphasis on hedonia and primary reward is giving way to diverse lines of research that focus on aspects of instrumental learning, reward prediction, incentive motivation, and behavioral activation. The present review discusses dopaminergic involvement in behavioral activation and, in particular, emphasizes the effort-related functions of nucleus accumbens DA and associated forebrain circuitry. The effects of accumbens DA depletions on food-seeking behavior are critically dependent upon the work requirements of the task. Lever pressing schedules that have minimal work requirements are largely unaffected by accumbens DA depletions, whereas reinforcement schedules that have high work (e.g., ratio) requirements are substantially impaired by accumbens DA depletions. Moreover, interference with accumbens DA transmission exerts a powerful influence over effort-related decision making. Rats with accumbens DA depletions reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and instead, these rats select a less-effortful type of food-seeking behavior. Along with prefrontal cortex and the amygdala, nucleus accumbens is a component of the brain circuitry regulating effort-related functions. Studies of the brain systems regulating effort-based processes may have implications for understanding drug abuse, as well as energy-related disorders such as psychomotor slowing, fatigue, or anergia in depression.

The Isolation and Characterization of Glycosylated Phosphoproteins from Herring Fish Bones*

PubMed Central

Zhou, Hai-Yan; Salih, Erdjan; Glimcher, Melvin J.

2010-01-01

Past studies of bone extracellular matrix phosphoproteins such as osteopontin and bone sialoprotein have yielded important biological information regarding their role in calcification and the regulation of cellular activity. Most of these studies have been limited to proteins extracted from mammalian and avian vertebrates and nonvertebrates. The present work describes the isolation and purification of two major highly glycosylated and phosphorylated extracellular matrix proteins of 70 and 22 kDa from herring fish bones. The 70-kDa phosphoprotein has some characteristics of osteopontin with respect to amino acid composition and susceptibility to thrombin cleavage. Unlike osteopontin, however, it was found to contain high levels of sialic acid similar to bone sialoprotein. The 22-kDa protein has very different properties such as very high content of phosphoserine (∼270 Ser(P) residues/1000 amino acid residues), Ala, and Asx residues. The N-terminal amino acid sequence analysis of both the 70-kDa (NPIMA(M)ETTS(M)DSKVNPLL) and the 22-kDa (NQDMAMEASSDPEAA) fish phosphoproteins indicate that these unique amino acid sequences are unlike any published in protein databases. An enzyme-linked immunosorbent assay revealed that the 70-kDa phosphoprotein was present principally in bone and in calcified scales, whereas the 22-kDa phosphoprotein was detected only in bone. Immunohistological analysis revealed diffusely positive immunostaining for both the 70- and 22-kDa phosphoproteins throughout the matrix of the bone. Overall, this work adds additional support to the concept that the mechanism of biological calcification has common evolutionary and fundamental bases throughout vertebrate species. PMID:20833721

Ecological Carrying Capacity of Land Use Changes in Da'an City

NASA Astrophysics Data System (ADS)

Wang, H.; Zhang, J.; Li, B.

2018-04-01

Based on GIS and RS technology, this paper analyzed the land use change in Da'an city from 1995 to 2010. land-use ecological evaluation index was constructed to evaluate the land-use ecological risk of Da 'an city dynamically, and the land-use ecological risk level map was made, and then the distribution and change of the land-use ecological carrying capacity pattern of Da'an city were analyzed qualitatively. According to the evaluation results of ecological carrying capacity, the ecological environment of Da'an city has deteriorated in fifteen years. in 1995, the poor ecological environment area is mainly distributed in the northeast area of Da'an city, and the area is small, while the area of the central and southern areas is large; In 2010, the western region also appeared environmental degradation, the northeast environment deterioration is serious, the dominant area is reduced, and a small amount of deterioration in the central and southern regions. According to the study of this paper, in the future, we should strengthen the comprehensive management of this part of the area, strengthen vegetation coverage, reduce soil erosion, ensure the effective improvement of ecological environment.

A Clinical Evaluation Denture Adhesives Used by Patients With Xerostomia

PubMed Central

Bogucki, Zdzislaw A.; Napadlek, Piotr; Dabrowa, Tomasz

2015-01-01

Abstract The purpose of study was to analyze the participants’ opinions concerning the effectiveness of 6 denture adhesives (DA). The study group included 60 participants. Criteria for selecting the patients were as follows: reduced retention and stabilization of maxillary complete dentures and xerostomia. These features were evaluated on basis of clinical examination and standard sialometry tests (u-SFR). Retention of maxillary dentures was scored by modified Kapur index before application of DA. All participants were divided randomly into 6 groups regarding the use of the 6 DA during a 6-month period. After this time, participants completed an HRQL questionnaire. DA noticeably improved retention and stabilization of maxillary complete dentures. DA in the glue form had the best retention effectiveness in participants with xerostomia. These materials are difficult to clean from the denture base. The data are presented in tables and figures. The results of the study collected positive influence of adhesives on retention of dentures in xerostomia patients. The cleaning dentures and denture bearing tissues was difficult. DA help in the use of prostheses, but it is also necessary for the treatment of the causes and symptoms of xerostomia. PMID:25700320

Field evaluation of descent advisor trajectory prediction accuracy

DOT National Transportation Integrated Search

1996-07-01

The Descent Advisor (DA) automation tool has undergone a series of field tests : at the Denver Air Route Traffic Control Center to study the feasibility of : DA-based clearances and procedures. The latest evaluation, conducted in the : fall of 1995, ...

The Ubiquitin Receptor DA1 Interacts with the E3 Ubiquitin Ligase DA2 to Regulate Seed and Organ Size in Arabidopsis[C][W

PubMed Central

Xia, Tian; Li, Na; Dumenil, Jack; Li, Jie; Kamenski, Andrei; Bevan, Michael W.; Gao, Fan; Li, Yunhai

2013-01-01

Seed size in higher plants is determined by the coordinated growth of the embryo, endosperm, and maternal tissue. Several factors that act maternally to regulate seed size have been identified, such as AUXIN RESPONSE FACTOR2, APETALA2, KLUH, and DA1, but the genetic and molecular mechanisms of these factors in seed size control are almost totally unknown. We previously demonstrated that the ubiquitin receptor DA1 acts synergistically with the E3 ubiquitin ligase ENHANCER1 OF DA1 (EOD1)/BIG BROTHER to regulate the final size of seeds in Arabidopsis thaliana. Here, we describe another RING-type protein with E3 ubiquitin ligase activity, encoded by DA2, which regulates seed size by restricting cell proliferation in the maternal integuments of developing seeds. The da2-1 mutant forms large seeds, while overexpression of DA2 decreases seed size of wild-type plants. Overexpression of rice (Oryza sativa) GRAIN WIDTH AND WEIGHT2, a homolog of DA2, restricts seed growth in Arabidopsis. Genetic analyses show that DA2 functions synergistically with DA1 to regulate seed size, but does so independently of EOD1. Further results reveal that DA2 interacts physically with DA1 in vitro and in vivo. Therefore, our findings define the genetic and molecular mechanisms of three ubiquitin-related proteins DA1, DA2, and EOD1 in seed size control and indicate that they are promising targets for crop improvement. PMID:24045020

Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease.

PubMed

Rhee, Yong-Hee; Ko, Ji-Yun; Chang, Mi-Yoon; Yi, Sang-Hoon; Kim, Dohoon; Kim, Chun-Hyung; Shim, Jae-Won; Jo, A-Young; Kim, Byung-Woo; Lee, Hyunsu; Lee, Suk-Ho; Suh, Wonhee; Park, Chang-Hwan; Koh, Hyun-Chul; Lee, Yong-Sung; Lanza, Robert; Kim, Kwang-Soo; Lee, Sang-Hun

2011-06-01

Parkinson disease (PD) involves the selective loss of midbrain dopamine (mDA) neurons and is a possible target disease for stem cell-based therapy. Human induced pluripotent stem cells (hiPSCs) are a potentially unlimited source of patient-specific cells for transplantation. However, it is critical to evaluate the safety of hiPSCs generated by different reprogramming methods. Here, we compared multiple hiPSC lines derived by virus- and protein-based reprogramming to human ES cells (hESCs). Neuronal precursor cells (NPCs) and dopamine (DA) neurons delivered from lentivirus-based hiPSCs exhibited residual expression of exogenous reprogramming genes, but those cells derived from retrovirus- and protein-based hiPSCs did not. Furthermore, NPCs derived from virus-based hiPSCs exhibited early senescence and apoptotic cell death during passaging, which was preceded by abrupt induction of p53. In contrast, NPCs derived from hESCs and protein-based hiPSCs were highly expandable without senescence. DA neurons derived from protein-based hiPSCs exhibited gene expression, physiological, and electrophysiological properties similar to those of mDA neurons. Transplantation of these cells into rats with striatal lesions, a model of PD, significantly rescued motor deficits. These data support the clinical potential of protein-based hiPSCs for personalized cell therapy of PD.

Independent components analysis to increase efficiency of discriminant analysis methods (FDA and LDA): Application to NMR fingerprinting of wine.

PubMed

Monakhova, Yulia B; Godelmann, Rolf; Kuballa, Thomas; Mushtakova, Svetlana P; Rutledge, Douglas N

2015-08-15

Discriminant analysis (DA) methods, such as linear discriminant analysis (LDA) or factorial discriminant analysis (FDA), are well-known chemometric approaches for solving classification problems in chemistry. In most applications, principle components analysis (PCA) is used as the first step to generate orthogonal eigenvectors and the corresponding sample scores are utilized to generate discriminant features for the discrimination. Independent components analysis (ICA) based on the minimization of mutual information can be used as an alternative to PCA as a preprocessing tool for LDA and FDA classification. To illustrate the performance of this ICA/DA methodology, four representative nuclear magnetic resonance (NMR) data sets of wine samples were used. The classification was performed regarding grape variety, year of vintage and geographical origin. The average increase for ICA/DA in comparison with PCA/DA in the percentage of correct classification varied between 6±1% and 8±2%. The maximum increase in classification efficiency of 11±2% was observed for discrimination of the year of vintage (ICA/FDA) and geographical origin (ICA/LDA). The procedure to determine the number of extracted features (PCs, ICs) for the optimum DA models was discussed. The use of independent components (ICs) instead of principle components (PCs) resulted in improved classification performance of DA methods. The ICA/LDA method is preferable to ICA/FDA for recognition tasks based on NMR spectroscopic measurements. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibition potential of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites on the in vitro monoamine oxidase (MAO)-catalyzed deamination of the neurotransmitters serotonin and dopamine.

PubMed

Steuer, Andrea E; Boxler, Martina I; Stock, Lorena; Kraemer, Thomas

2016-01-22

Neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA) is still controversially discussed. Formation of reactive oxygen species e.g. based on elevated dopamine (DA) concentrations and DA quinone formation is discussed among others. Inhibition potential of MDMA metabolites regarding neurotransmitter degradation by catechol-O-methyltransferase and sulfotransferase was described previously. Their influence on monoamine oxidase (MAO) - the major DA degradation pathway-has not yet been studied in humans. Therefore the inhibition potential of MDMA and its metabolites on the deamination of the neurotransmitters DA and serotonin (5-HT) by MAO-A and B using recombinant human enzymes in vitro should be investigated. In initial studies, MDMA and MDA showed relevant inhibition (>30%) toward MAO A for 5-HT and DA. No relevant effects toward MAO B were observed. Further investigation on MAO-A revealed MDMA as a competitive inhibitor of 5-HT and DA deamination with Ki 24.5±7.1 μM and 18.6±4.3 μM respectively and MDA as a mixed-type inhibitor with Ki 7.8±2.6 μM and 8.4±3.2 μM respectively. Although prediction of in vivo relevance needs to be done with care, relevant inhibitory effects at expected plasma concentrations after recreational MDMA consumption seems unlikely based on the obtained data. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

PanDA Pilot Submission using Condor-G: Experience and Improvements

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

Zhao X.; Hover John; Wlodek Tomasz

2011-01-01

PanDA (Production and Distributed Analysis) is the workload management system of the ATLAS experiment, used to run managed production and user analysis jobs on the grid. As a late-binding, pilot-based system, the maintenance of a smooth and steady stream of pilot jobs to all grid sites is critical for PanDA operation. The ATLAS Computing Facility (ACF) at BNL, as the ATLAS Tier1 center in the US, operates the pilot submission systems for the US. This is done using the PanDA 'AutoPilot' scheduler component which submits pilot jobs via Condor-G, a grid job scheduling system developed at the University of Wisconsin-Madison.more » In this paper, we discuss the operation and performance of the Condor-G pilot submission at BNL, with emphasis on the challenges and issues encountered in the real grid production environment. With the close collaboration of Condor and PanDA teams, the scalability and stability of the overall system has been greatly improved over the last year. We review improvements made to Condor-G resulting from this collaboration, including isolation of site-based issues by running a separate Gridmanager for each remote site, introduction of the 'Nonessential' job attribute to allow Condor to optimize its behavior for the specific character of pilot jobs, better understanding and handling of the Gridmonitor process, as well as better scheduling in the PanDA pilot scheduler component. We will also cover the monitoring of the health of the system.« less

Limitations of Mass Spectrometry-Based Peptidomic Approaches

NASA Astrophysics Data System (ADS)

Fricker, Lloyd D.

2015-12-01

Mass spectrometry-based peptidomic approaches are powerful techniques to detect and identify the peptide content of biological samples. The present study investigated the limitations of peptidomic approaches using trimethylammonium butyrate isotopic tags to quantify relative peptide levels and Mascot searches to identify peptides. Data were combined from previous studies on human cell lines or mouse tissues. The combined databases contain 2155 unique peptides ranging in mass from 444 to 8765 Da, with the vast majority between 1 and 3 kDa. The amino acid composition of the identified peptides generally reflected the frequency in the Eukaryotic proteome with the exception of Cys, which was not present in any of the identified peptides in the free-SH form but was detected at low frequency as a disulfide with Cys residues, a disulfide with glutathione, or as S-cyanocysteine. To test if the low detection rate of peptides smaller than 500 Da, larger than 3 kDa, or containing Cys was a limitation of the peptidomics procedure, tryptic peptides of known proteins were processed for peptidomics using the same approach used for human cell lines and mouse tissues. The identified tryptic peptides ranged from 516 to 2418 Da, whereas the theoretical digest ranged from 217 to 7559 Da. Peptides with Cys were rarely detected and, if present, the Cys was usually modified S-cyanocysteine. Additionally, peptides with mono- and di-iodo Tyr and His were identified. Taken together, there are limitations of peptidomic techniques, and awareness of these limitations is important to properly use and interpret results.

Global and disease-associated genetic variation in the human Fanconi anemia gene family

PubMed Central

Rogers, Kai J.; Fu, Wenqing; Akey, Joshua M.; Monnat, Raymond J.

2014-01-01

Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population genetic variation in FANC genes and the segregation of this variation in the human population, we identified 2948 unique FANC gene variants including 493 FA DA variants across 57 240 potential base pair variation sites in the 16 FANC genes. We then analyzed the segregation of this variation in the 7578 subjects included in the Exome Sequencing Project (ESP) and the 1000 Genomes Project (1KGP). There was a remarkably high frequency of FA DA variants in ESP/1KGP subjects: at least 1 FA DA variant was identified in 78.5% (5950 of 7578) individuals included in these two studies. Six widely used functional prediction algorithms correctly identified only a third of the known, DA FANC missense variants. We also identified FA DA variants that may be good candidates for different types of mutation-specific therapies. Our results demonstrate the power of direct DNA sequencing to detect, estimate the frequency of and follow the segregation of deleterious genetic variation in human populations. PMID:25104853

VerSeDa: vertebrate secretome database

PubMed Central

Cortazar, Ana R.; Oguiza, José A.

2017-01-01

Based on the current tools, de novo secretome (full set of proteins secreted by an organism) prediction is a time consuming bioinformatic task that requires a multifactorial analysis in order to obtain reliable in silico predictions. Hence, to accelerate this process and offer researchers a reliable repository where secretome information can be obtained for vertebrates and model organisms, we have developed VerSeDa (Vertebrate Secretome Database). This freely available database stores information about proteins that are predicted to be secreted through the classical and non-classical mechanisms, for the wide range of vertebrate species deposited at the NCBI, UCSC and ENSEMBL sites. To our knowledge, VerSeDa is the only state-of-the-art database designed to store secretome data from multiple vertebrate genomes, thus, saving an important amount of time spent in the prediction of protein features that can be retrieved from this repository directly. Database URL: VerSeDa is freely available at http://genomics.cicbiogune.es/VerSeDa/index.php PMID:28365718

Next Generation Workload Management and Analysis System for Big Data

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

De, Kaushik

We report on the activities and accomplishments of a four-year project (a three-year grant followed by a one-year no cost extension) to develop a next generation workload management system for Big Data. The new system is based on the highly successful PanDA software developed for High Energy Physics (HEP) in 2005. PanDA is used by the ATLAS experiment at the Large Hadron Collider (LHC), and the AMS experiment at the space station. The program of work described here was carried out by two teams of developers working collaboratively at Brookhaven National Laboratory (BNL) and the University of Texas at Arlingtonmore » (UTA). These teams worked closely with the original PanDA team – for the sake of clarity the work of the next generation team will be referred to as the BigPanDA project. Their work has led to the adoption of BigPanDA by the COMPASS experiment at CERN, and many other experiments and science projects worldwide.« less

Music improves dopaminergic neurotransmission: demonstration based on the effect of music on blood pressure regulation.

PubMed

Sutoo, Den'etsu; Akiyama, Kayo

2004-08-06

The mechanism by which music modifies brain function is not clear. Clinical findings indicate that music reduces blood pressure in various patients. We investigated the effect of music on blood pressure in spontaneously hypertensive rats (SHR). Previous studies indicated that calcium increases brain dopamine (DA) synthesis through a calmodulin (CaM)-dependent system. Increased DA levels reduce blood pressure in SHR. In this study, we examined the effects of music on this pathway. Systolic blood pressure in SHR was reduced by exposure to Mozart's music (K.205), and the effect vanished when this pathway was inhibited. Exposure to music also significantly increased serum calcium levels and neostriatal DA levels. These results suggest that music leads to increased calcium/CaM-dependent DA synthesis in the brain, thus causing a reduction in blood pressure. Music might regulate and/or affect various brain functions through dopaminergic neurotransmission, and might therefore be effective for rectification of symptoms in various diseases that involve DA dysfunction.

VerSeDa: vertebrate secretome database.

PubMed

Cortazar, Ana R; Oguiza, José A; Aransay, Ana M; Lavín, José L

2017-01-01

Based on the current tools, de novo secretome (full set of proteins secreted by an organism) prediction is a time consuming bioinformatic task that requires a multifactorial analysis in order to obtain reliable in silico predictions. Hence, to accelerate this process and offer researchers a reliable repository where secretome information can be obtained for vertebrates and model organisms, we have developed VerSeDa (Vertebrate Secretome Database). This freely available database stores information about proteins that are predicted to be secreted through the classical and non-classical mechanisms, for the wide range of vertebrate species deposited at the NCBI, UCSC and ENSEMBL sites. To our knowledge, VerSeDa is the only state-of-the-art database designed to store secretome data from multiple vertebrate genomes, thus, saving an important amount of time spent in the prediction of protein features that can be retrieved from this repository directly. VerSeDa is freely available at http://genomics.cicbiogune.es/VerSeDa/index.php. © The Author(s) 2017. Published by Oxford University Press.

Pyrimidine-based twisted donor-acceptor delayed fluorescence molecules: a new universal platform for highly efficient blue electroluminescence.

PubMed

Park, In Seob; Komiyama, Hideaki; Yasuda, Takuma

2017-02-01

Deep-blue emitters that can harvest both singlet and triplet excited states to give high electron-to-photon conversion efficiencies are highly desired for applications in full-color displays and white lighting devices based on organic light-emitting diodes (OLEDs). Thermally activated delayed fluorescence (TADF) molecules based on highly twisted donor-acceptor (D-A) configurations are promising emitting dopants for the construction of efficient deep-blue OLEDs. In this study, a simple and versatile D-A system combining acridan-based donors and pyrimidine-based acceptors has been developed as a new platform for high-efficiency deep-blue TADF emitters. The designed pre-twisted acridan-pyrimidine D-A molecules exhibit small singlet-triplet energy splitting and high photoluminescence quantum yields, functioning as efficient deep-blue TADF emitters. The OLEDs utilizing these TADF emitters display bright blue electroluminescence with external quantum efficiencies of up to 20.4%, maximum current efficiencies of 41.7 cd A -1 , maximum power efficiencies of 37.2 lm W -1 , and color coordinates of (0.16, 0.23). The design strategy featuring such acridan-pyrimidine D-A motifs can offer great prospects for further developing high-performance deep-blue TADF emitters and TADF-OLEDs.

Effects of omeprazole or cola beverage on the pharmacokinetics of oral DA-8159, a new erectogenic, in rats.

PubMed

Lee, Joo H; Bae, Soo K; Kwon, Jong W; Kim, Won B; Lee, Myung G

2005-12-01

The changes in pharmacokinetics of DA-8159 by omeprazole with respect to inhibition of CYP3A1/2 in rats were evaluated. After oral administration of DA-8159 at dose of 30 mg/kg to rats pretreated with oral omeprazole at 30 mg/kg for 1 week, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) of DA-8159 was significantly greater (37.5% increase) than that in control rats. This could be due to inhibition of metabolism of DA-8159 by inhibition of CYP3A1/2 by omeprazole. The AUC(DA-8164 (a metabolite of DA-8159))/AUC(DA-8159) ratio was also smaller (32.4% decrease) with omeprazole. After oral administration of DA-8159 at a dose of 30 mg/kg to rats without or with cola beverage, the pharmacokinetic parameters of DA-8159 and DA-8164 were not significantly different between two groups of rats. This suggested that cola beverage did not have any considerable effects on CYP3A1/2 in rats.

The Douro estuarine plume: Detection, processes and dynamics =

NASA Astrophysics Data System (ADS)

Mendes, Renato Paulo dos Santos

O Douro e um dos maiores rios da Peninsula Iberica, constituindo a maior descarga de agua doce para o Oceano Atlântico na costa noroeste portuguesa. A sua pluma estuarina tem particular relevância na dinâmica costeira e na modulacao de fenomenos biogeoquimicos. Sao objetivos desta dissertacao contribuir para a compreensao dos processos fisicos associados a geracao e propagacao da pluma estuarina do Rio Douro no oceano, assim como para o conhecimento dos seus padroes de dispersao e da forma como estes alteram a hidrologia e a circulacao costeira, considerando os agentes forcadores tipicos deste fenomeno (caudal fluvial, vento e mare) e indices climaticos relevantes. Para concretizacao destes objetivos foram desenvolvidas e aplicadas metodologias inovadoras de processamento de dados de detecao remota, assim como novas implementacoes estuarinas e costeiras de modelos numericos. Atraves de imagens MODIS, otimizadas para o estudo de fenomenos costeiros, efetuou-se uma detecao rigorosa da pluma. Identificou-se uma relacao entre o sinal turbido nLw555 e o caudal, demonstrando-se este produto como um bom proxy para a observacao da pluma no oceano. As escalas temporais e espaciais da pluma foram caraterizadas atraves destas imagens, combinadas com dados de caudal fluvial, mare, vento e precipitacao, e tambem com indices climaticos relevantes. Para compreender a propagacao da pluma e caracterizar a sua dinâmica e impacto na circulacao costeira, foi desenvolvida uma aplicacao 3D de modelos estuarinos e costeiros com malhas aninhadas de resolucao variavel. Definiramse e analisaram-se diferentes cenarios de vento e descarga fluvial. A interacao da pluma do Rio Douro e do Minho foi ainda analisada atraves dos resultados de simulacoes baseadas num evento de inverno. Os compositos turbidos mostraram que a pluma e facilmente detetada quando o caudal e maior que 500 m3 s??1. A descarga fluvial e o vento sao os principais forcadores da sua propagacao, enquanto a mare e apenas importante na regiao proxima a embocadura do estuario. Observaram-se relacoes a uma escala interanual entre a turbidez da pluma e os indices climaticos East Atlantic e NAO, com uma correlacao maxima identificada com 1 e 3 meses de desfasamento, respetivamente. Com base nos resultados das simulacoes efetuadas, a pluma e classificada como de larga escala e de advecao superficial, apresentando caracteristicas de uma pluma prototipica. Em condicoes de caudal moderado a elevado, a descarga estuarina e suficiente para gerar uma corrente costeira para norte sem acao do vento. Em eventos de ventos leste, a propagacao da pluma e similar ao caso sem vento, com um aumento da velocidade da corrente. Uma corrente costeira para sul e unicamente identificada sob condicoes de forte vento de oeste. Ventos de norte tendem a estender a pluma para o largo, com uma inclinacao na direcao sudoeste, enquanto ventos de sul intensificam a corrente para norte, sendo a mistura das plumas do Douro e do Minho uma consequencia possivel. A analise desta interacao apontou a contribuicao do Douro como importante na estabilizacao da WIBP e nas trocas de agua entre o oceano e as Rias Baixas. A interacao da pluma do Douro com estuarios localizados a sul da sua foz e a confirmacao in situ da recirculacao observada nos resultados numericos afiguram-se como temas relevantes para investigacoes futuras. None

75 FR 75868 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

... Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes AGENCY: Federal... of the Thielert Engine Owners Group commented that the Model DA 42 has the same door design and the same unsafe condition. He recommended that the AD also apply to the Model DA 42. The FAA has discussed...

Characterization of low molecular weight fragments from gamma irradiated κ-carrageenan used as plant growth promoter

NASA Astrophysics Data System (ADS)

Abad, Lucille V.; Aurigue, Fernando B.; Relleve, Lorna S.; Montefalcon, Djowel Recto V.; Lopez, Girlie Eunice P.

2016-01-01

Radiation degraded κ-carrageenan (1% solution at absorbed doses of 20 kGy and 30 kGy) were tested for its plant growth promoter (PGP) effect on pechay plants under hydroponics condition. Results revealed that higher PGP effects were found in κ-carrageenan irradiated at an absorbed dose of 30 kGy. Mw of irradiated κ-carrageenan as measured by GPC were determined to be 7362 Da and 6762 Da for 20 kGy and 30 kGy, respectively. Fractionation of the irradiated κ-carrageenan (30 kGy) was done to separate different Mw fractions using Mw cut-off filters of 1 kDa, 3 kDa, and 5 kDa. The PGP effect of the different retentates showed that biological activity in plants followed the order of 5 kDa>3 kDa>1 kDa using hydroponics condition but the reverse was observed in the order of 1 kDa>3 kDa>5 kDa when absorbed in plants by foliar spraying. GPC chromatogram indicated at least three (3) low molecular weight (LMW) fragments from radiation modified κ-carrageenan solution with an Mw<2000 Da. A fragment has also been identified with an Mw of as low as 160 Da which was produced under acidic (un-neutralized) condition. This may be attributed to the formation of 5-hydroxymethylfurfural (5-HMF).

The role of N-methyl-D-aspartate receptors and nitric oxide in cochlear dopamine release.

PubMed

Halmos, G; Horváth, T; Polony, G; Fekete, A; Kittel, A; Vizi, E S; van der Laan, B F A M; Zelles, T; Lendvai, B

2008-06-23

Dopamine (DA) released from lateral olivocochlear (LOC) terminals may have a neuroprotective effect in the cochlea. To explore the role of N-methyl-d-aspartate (NMDA) receptors and nitric oxide (NO) in the modulation of a cochlear DA release, we measured the release of [3H]DA from isolated mouse cochlea in response to the application of NMDA. NMDA at 100 muM significantly increased the electrical-field stimulation-evoked and resting release of DA from the cochlea. The NO donor sodium nitroprusside enhanced the basal outflow of DA but failed to influence the evoked release. The administration of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) alone was ineffective, but it significantly inhibited the initial phase of the NMDA-induced elevation of DA outflow, which suggested the role of NO in the NMDA-induced DA release. The DA uptake inhibitor nomifensine increased the electrically evoked release of DA. Nomifensine failed to change the effect of NMDA on the resting or electrically-evoked DA release, which suggested that the uptake mechanism does not play a role in NMDA-evoked and NO-mediated DA release. In summary, we provide evidence that NO can modulate the release of DA from the cochlea following NMDA receptor activation, but does not affect the uptake of DA.

Amyloid beta precursor protein and ubiquitin epitopes in human and experimental dystrophic axons. Ultrastructural localization.

PubMed Central

Bacci, B.; Cochran, E.; Nunzi, M. G.; Izeki, E.; Mizutani, T.; Patton, A.; Hite, S.; Sayre, L. M.; Autilio-Gambetti, L.; Gambetti, P.

1994-01-01

Dystrophic axons (DA) represent a major pathological feature of several neurodegenerative disorders, including infantile neuroaxonal dystrophy (INAD) and Alzheimer disease. We have previously presented evidence that amyloid beta precursor protein (BPP) and ubiquitin (Ub) are present in DA of different origin. We have now characterized the immunoreactivity of DA experimentally induced in rat by the administration of parabromophenylacetylurea (BPAU) and examined the subcellular localization of Ub and BPP in BPAU-induced DA and in DA present in subjects affected by INAD. BPAU-induced DA strongly immunoreacted with antisera to Ub and to COOH- and NH2-terminal regions of BPP. Immunoblots of DA-enriched brain regions were consistent with an increase in the amount of Ub and BPP in DA. Moreover, BPAU-induced DA immunoreacted with antibodies to PGP 9.5, a neuronal-specific Ub COOH-terminal hydrolase, and to the inducible heat shock protein 70. Antigenic characterization also indicated that the tubulovesicular membranes within DA derived largely from the smooth endoplasmic reticulum rather than from the Golgi system or the synaptic vesicles. Subcellular immunolocalization of Ub and BPP in both INAD- and BPAU-induced DA revealed that Ub and BPP colocalize in granulovesicular material in both conditions. In INAD DA intense Ub immunoreactivity was also detected in nonmembranous electron dense structures that were present only in these DA, probably because of the chronic course of INAD. Although BPP immunostaining may be related to accumulation of BPP-containing membranes in DA, Ub immunostaining is likely to result from activation of the Ub system by the neuron in the attempt to remove excessive and possibly abnormal proteins. A similar pathogenesis can be postulated for DA of Alzheimer disease. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7512790

Molecular modeling and molecular dynamics simulations based structural analysis of the SG2NA protein variants.

PubMed

Soni, Sangeeta; Tyagi, Chetna; Grover, Abhinav; Goswami, Shyamal K

2014-07-11

SG2NA is a member of the striatin sub-family of WD-40 repeat proteins. Striatin family members have been associated with diverse physiological functions. SG2NA has also been shown to have roles in cell cycle progression, signal transduction etc. They have been known to interact with a number of proteins including Caveolin and Calmodulin and also propagate the formation of a multimeric protein unit called striatin-interacting phosphatase and kinase. As a pre-requisite for such interaction ability, these proteins are known to be unstable and primarily disordered in their arrangement. Earlier we had identified that it has multiple isoforms (namely 35, 78, 87 kDa based on its molecular weight) which are generated by alternative splicing. However, detailed structural information of SG2NA is still eluding the researchers. This study was aimed towards three-dimensional molecular modeling and characterization of SG2NA protein and its isoforms. One structure out of five was selected for each variant having the least value for C score. Out of these, m35 kDa with a C score value of -3.21 was the most poorly determined structure in comparison to m78 kDa and m87 kDa variants with C scores of -1.16 and -1.97 respectively. Further evaluation resulted in about 61.6% residues of m35 kDa, 76.6% residues of m78 kDa and 72.1% residues of m87 kDa falling in the favorable regions of Ramchandran Plot. Molecular dynamics simulations were also carried out to obtain biologically relevant structural models and compared with previous atomic coordinates. N-terminal region of all variants was found to be highly disordered. This study provides first-hand detailed information to understand the structural conformation of SG2NA protein variants (m35 kDa, m78 kDa and m87 kDa). The WD-40 repeat domain was found to constitute antiparallel strands of β-sheets arranged circularly. This study elucidates the crucial structural features of SG2NA proteins which are involved in various protein-protein interactions and also reveals the extent of disorder present in the SG2NA structure crucial for excessive interaction and multimeric protein complexes. The study also potentiates the role of computational approaches for preliminary examination of unknown proteins in the absence of experimental information.

Enhanced peroxydisulfate electrochemiluminescence for dopamine biosensing based on Au nanoparticle decorated reduced graphene oxide.

PubMed

Yan, Yuting; Liu, Qian; Wang, Kun; Jiang, Ling; Yang, Xingwang; Qian, Jing; Dong, Xiaoya; Qiu, Baijing

2013-12-07

This work reports a novel strategy to amplify the electrochemiluminescence (ECL) signal of peroxydisulfate solution based on the Au nanoparticle decorated reduced graphene oxide (Au NP-RGO), and further an ECL biosensor for sensitive and selective detection of dopamine (DA) was constructed. Due to the synergistic amplification of Au NPs and RGO, the ECL signal of peroxydisulfate solution on the Au NP-RGO modified electrode was about 5-fold enhanced compared to that of the bare electrode with the ECL onset potential positively shifted from -1.2 V to -0.9 V. More interestingly, the ECL intensity of peroxydisulfate solution increased with the increase of DA concentration, based on which an ECL biosensor for DA determination was fabricated. The as-prepared solid-state ECL DA sensor showed a wide linear response of 0.02-40 μM with a detection limit of 6.7 nM (S/N = 3). Moreover, we expect this work would open up a new field in the application of peroxydisulfate solution ECL for highly sensitive bioassays.

Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons

PubMed Central

Steinkellner, Thomas; Farino, Zachary J.; Sonders, Mark S.; Villeneuve, Michael; Freyberg, Robin J.; Przedborski, Serge; Lu, Wei; Hnasko, Thomas S.

2018-01-01

Parkinson’s disease is characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). DA neurons in the ventral tegmental area are more resistant to this degeneration than those in the SNc, though the mechanisms for selective resistance or vulnerability remain poorly understood. A key to elucidating these processes may lie within the subset of DA neurons that corelease glutamate and express the vesicular glutamate transporter VGLUT2. Here, we addressed the potential relationship between VGLUT expression and DA neuronal vulnerability by overexpressing VGLUT in DA neurons of flies and mice. In Drosophila, VGLUT overexpression led to loss of select DA neuron populations. Similarly, expression of VGLUT2 specifically in murine SNc DA neurons led to neuronal loss and Parkinsonian behaviors. Other neuronal cell types showed no such sensitivity, suggesting that DA neurons are distinctively vulnerable to VGLUT2 expression. Additionally, most DA neurons expressed VGLUT2 during development, and coexpression of VGLUT2 with DA markers increased following injury in the adult. Finally, conditional deletion of VGLUT2 made DA neurons more susceptible to Parkinsonian neurotoxins. These data suggest that the balance of VGLUT2 expression is a crucial determinant of DA neuron survival. Ultimately, manipulation of this VGLUT2-dependent process may represent an avenue for therapeutic development. PMID:29337309

MK-801 protection against methamphetamine-induced striatal dopamine terminal injury is associated with attenuated dopamine overflow.

PubMed

Weihmuller, F B; O'Dell, S J; Marshall, J F

1992-06-01

Repeated administrations of methamphetamine (m-AMPH) produce high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. Pharmacological blockade of N-methyl-D-aspartate (NMDA) receptors has been shown previously to prevent m-AMPH-induced striatal DA terminal injury, but the mechanism for this protection is unclear. In the present study, in vivo microdialysis was used to determine the effects of blockade of NMDA receptors with the noncompetitive antagonist MK-801 on m-AMPH-induced striatal DA overflow. Four injections of MK-801 (0.5 mg/kg, ip) alone did not significantly change extracellular striatal DA concentrations from pretreatment values. Four treatments with m-AMPH (4.0 mg/kg, sc at 2-hr intervals) increased striatal DA overflow, and the overflow was particularly extensive following the fourth injection. This m-AMPH regimen produced a 40% reduction in striatal DA tissue content 1 week later. Treatment with MK-801 15 min before each of the four m-AMPH injections or prior to only the last two m-AMPH administrations attenuated the m-AMPH-induced increase in striatal DA overflow and protected completely against striatal DA depletions. Other MK-801 treatment regimens less effectively reduced the m-AMPH-induced striatal DA efflux and were ineffective in protecting against striatal DA depletions. Linear regression analysis indicated that cumulative DA overflow was strongly predictive (r = -.68) of striatal DA tissue levels measured one week later. These findings suggest that the extensive DA overflow seen during a neurotoxic regimen of m-AMPH is a crucial component of the subsequent neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterogeneities in Axonal Structure and Transporter Distribution Lower Dopamine Reuptake Efficiency

PubMed Central

Block, Ethan R.; Bartol, Tom M.; Sorkin, Alexander

2018-01-01

Abstract Efficient clearance of dopamine (DA) from the synapse is key to regulating dopaminergic signaling. This role is fulfilled by DA transporters (DATs). Recent advances in the structural characterization of DAT from Drosophila (dDAT) and in high-resolution imaging of DA neurons and the distribution of DATs in living cells now permit us to gain a mechanistic understanding of DA reuptake events in silico. Using electron microscopy images and immunofluorescence of transgenic knock-in mouse brains that express hemagglutinin-tagged DAT in DA neurons, we reconstructed a realistic environment for MCell simulations of DA reuptake, wherein the identity, population and kinetics of homology-modeled human DAT (hDAT) substates were derived from molecular simulations. The complex morphology of axon terminals near active zones was observed to give rise to large variations in DA reuptake efficiency, and thereby in extracellular DA density. Comparison of the effect of different firing patterns showed that phasic firing would increase the probability of reaching local DA levels sufficiently high to activate low-affinity DA receptors, mainly owing to high DA levels transiently attained during the burst phase. The experimentally observed nonuniform surface distribution of DATs emerged as a major modulator of DA signaling: reuptake was slower, and the peaks/width of transient DA levels were sharper/wider under nonuniform distribution of DATs, compared with uniform. Overall, the study highlights the importance of accurate descriptions of extrasynaptic morphology, DAT distribution, and conformational kinetics for quantitative evaluation of dopaminergic transmission and for providing deeper understanding of the mechanisms that regulate DA transmission. PMID:29430519

Modafinil Activates Phasic Dopamine Signaling in Dorsal and Ventral Striata

PubMed Central

Bobak, Martin J.; Weber, Matthew W.; Doellman, Melissa A.; Schuweiler, Douglas R.; Athens, Jeana M.; Juliano, Steven A.

2016-01-01

Modafinil (MOD) exhibits therapeutic efficacy for treating sleep and psychiatric disorders; however, its mechanism is not completely understood. Compared with other psychostimulants inhibiting dopamine (DA) uptake, MOD weakly interacts with the dopamine transporter (DAT) and modestly elevates striatal dialysate DA, suggesting additional targets besides DAT. However, the ability of MOD to induce wakefulness is abolished with DAT knockout, conversely suggesting that DAT is necessary for MOD action. Another psychostimulant target, but one not established for MOD, is activation of phasic DA signaling. This communication mode during which burst firing of DA neurons generates rapid changes in extracellular DA, the so-called DA transients, is critically implicated in reward learning. Here, we investigate MOD effects on phasic DA signaling in the striatum of urethane-anesthetized rats with fast-scan cyclic voltammetry. We found that MOD (30–300 mg/kg i.p.) robustly increases the amplitude of electrically evoked phasic-like DA signals in a time- and dose-dependent fashion, with greater effects in dorsal versus ventral striata. MOD-induced enhancement of these electrically evoked amplitudes was mediated preferentially by increased DA release compared with decreased DA uptake. Principal component regression of nonelectrically evoked recordings revealed negligible changes in basal DA with high-dose MOD (300 mg/kg i.p.). Finally, in the presence of the D2 DA antagonist, raclopride, low-dose MOD (30 mg/kg i.p.) robustly elicited DA transients in dorsal and ventral striata. Taken together, these results suggest that activation of phasic DA signaling is an important mechanism underlying the clinical efficacy of MOD. PMID:27733628

Pervaporative dehydration characteristics of an ethanol/water azeotrope through various chitosan membranes.

PubMed

Uragami, Tadashi; Saito, Tomoyuki; Miyata, Takashi

2015-04-20

The permeation and separation characteristics of an ethanol/water azeotrope through chitosan membranes of different molecular weights and degrees of deacetylation during pervaporation were investigated. The normalized permeation rate decreased with increasing molecular weight up to 90 kDa, but at over 90 kDa, the rate increased. On the other hand, the water/ethanol selectivity increased with increasing molecular weight up to 90 kDa but decreased at over 90 kDa. With increasing degree of deacetylation, the water/ethanol permselectivity increased significantly, but the normalized permeation rate decreased. The characteristics of chitosan membranes are discussed based on their chemical and physical structures such as the contact angle, density, degree of swelling, and glass transition temperature. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genomic position affects the expression of tobacco mosaic virus movement and coat protein genes.

PubMed Central

Culver, J N; Lehto, K; Close, S M; Hilf, M E; Dawson, W O

1993-01-01

Alterations in the genomic position of the tobacco mosaic virus (TMV) genes encoding the 30-kDa cell-to-cell movement protein or the coat protein greatly affected their expression. Higher production of 30-kDa protein was correlated with increased proximity of the gene to the viral 3' terminus. A mutant placing the 30-kDa open reading frame 207 nucleotides nearer the 3' terminus produced at least 4 times the wild-type TMV 30-kDa protein level, while a mutant placing the 30-kDa open reading frame 470 nucleotides closer to the 3' terminus produced at least 8 times the wild-type TMV 30-kDa protein level. Increases in 30-kDa protein production were not correlated with the subgenomic mRNA promoter (SGP) controlling the 30-kDa gene, since mutants with either the native 30-kDa SGP or the coat protein SGP in front of the 30-kDa gene produced similar levels of 30-kDa protein. Lack of coat protein did not affect 30-kDa protein expression, since a mutant with the coat protein start codon removed did not produce increased amounts of 30-kDa protein. Effects of gene positioning on coat protein expression were examined by using a mutant containing two different tandemly positioned tobamovirus (TMV and Odontoglossum ringspot virus) coat protein genes. Only coat protein expressed from the gene positioned nearest the 3' viral terminus was detected. Analysis of 30-kDa and coat protein subgenomic mRNAs revealed no proportional increase in the levels of mRNA relative to the observed levels of 30-kDa and coat proteins. This suggests that a translational mechanism is primarily responsible for the observed effect of genomic position on expression of 30-kDa movement and coat protein genes. Images Fig. 2 Fig. 3 Fig. 4 PMID:8446627

Complete nucleotide sequence of jasmine virus H, a new member of the family Tombusviridae.

PubMed

Zhuo, Tao; Zhu, Li-Juan; Lu, Cheng-Cong; Jiang, Chao-Yang; Chen, Zi-Yin; Zhang, Guangzhi; Wang, Zong-Hua; Jovel, Juan; Han, Yan-Hong

2018-03-01

Jasmine virus H (JaVH) is a novel virus associated with symptoms of yellow mosaic on jasmine. The JaVH genome is 3,867 nt in length with five open reading frames (ORFs) encoding a 27-kDa protein (ORF 1), an 87-kDa replicase protein (ORF 2), two centrally located movement proteins (ORF 3 and 4), and a 37-kDa capsid protein (ORF 5). Based on genomic and phylogenetic analysis, JaVH is predicted to be a member of the genus Pelarspovirus in the family Tombusviridae.

The effect of continuous positive airway pressure on middle ear pressure.

PubMed

Lin, Fred Y; Gurgel, Richard K; Popelka, Gerald R; Capasso, Robson

2012-03-01

While continuous positive airway pressure (CPAP) is commonly used for obstructive sleep apnea treatment, its effect on middle ear pressure is unknown. The purpose of this study was to measure the effect of CPAP on middle ear pressure and describe the correlation between CPAP levels and middle ear pressures. Retrospective review of normal tympanometry values and a prospective cohort evaluation of subjects' tympanometric values while using CPAP at distinct pressure levels. A total of 3,066 tympanograms were evaluated to determine the normal range of middle ear pressures. Ten subjects with no known history of eustachian tube dysfunction or obstructive sleep apnea had standard tympanometry measurements while wearing a CPAP device. Measurements were taken at baseline and with CPAP air pressures of 0, 5, 10, and 15 cm H(2)O. The percentage of normal control patients with middle ear pressures above 40 daPa was 0.03%. In the study population, prior to a swallowing maneuver to open the eustachian tube, average middle ear pressures were 21.67 daPa, 22.63 daPa, 20.42, daPa, and 21.58 daPa with CPAP pressures of 0, 5, 10, and 15 cm H(2) 0, respectively. After swallowing, average middle ear air pressures were 18.83 daPa, 46.75 daPa, 82.17 daPa, and 129.17 daPa with CPAP pressures of 0, 5, 10, and 15 cm H(2)0, respectively. The postswallow Pearson correlation coefficient correlating CPAP and middle ear pressures was 0.783 (P < 0.001). Middle ear air pressure is directly proportional to CPAP air pressure in subjects with normal eustachian tube function. Middle ear pressure reaches supraphysiologic levels at even minimal CPAP levels. Although further investigation is necessary, there may be otologic implications for patients who are chronically CPAP dependent. These findings may also influence the perioperative practice of otologic and skull base surgeons. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Improved cell therapy protocol for Parkinson’s disease based on differentiation efficiency and safety of hESC-, hiPSC and non-human primate iPSC-derived DA neurons

PubMed Central

Maria, Sundberg; Helle, Bogetofte; Tristan, Lawson; Gaynor, Smith; Arnar, Astradsson; Michele, Moore; Teresia, Osborn; Oliver, Cooper; Roger, Spealman; Penelope, Hallett; Ole, Isacson

2013-01-01

The main motor symptoms of Parkinson’s disease are due to the loss of dopaminergic (DA) neurons in the ventral midbrain (VM). For the future treatment of Parkinson’s disease with cell transplantation it is important to develop efficient differentiation methods for production of human iPSCs and hESCs-derived midbrain-type DA neurons. Here we describe an efficient differentiation and sorting strategy for DA-neurons from both human ES/iPS cells and non-human primate iPSCs. The use of non-human primate iPSCs for neuronal differentiation and autologous transplantation is important for pre-clinical evaluation of safety and efficacy of stem cell-derived DA neurons. The aim of this study was to improve the safety of human- and non-human primate-iPSC (PiPSC)-derived DA neurons. According to our results, NCAM+/CD29low sorting enriched VM DA-neurons from pluripotent stem cell-derived neural cell populations. NCAM+/CD29low DA-neurons were positive for FOXA2/TH and EN1/TH and this cell population had increased expression levels of FOXA2, LMX1A, TH, GIRK2, PITX3, EN1, NURR1 mRNA compared to unsorted neural cell populations. PiPSC-derived NCAM+/CD29low DA-neurons were able to restore motor function of 6-OHDA lesioned rats 16 weeks after transplantation. The transplanted sorted cells also integrated in the rodent brain tissue, with robust TH+/hNCAM+ neuritic innervation of the host striatum. One year after autologous transplantation, the primate iPSC-derived neural cells survived in the striatum of one primate without any immunosuppression. These neural cell grafts contained FOXA2/TH-positive neurons in the graft site. This is an important proof of concept for the feasibility and safety of iPSC-derived cell transplantation therapies in the future. PMID:23666606

Tree Branching: Leonardo da Vinci's Rule versus Biomechanical Models

PubMed Central

Minamino, Ryoko; Tateno, Masaki

2014-01-01

This study examined Leonardo da Vinci's rule (i.e., the sum of the cross-sectional area of all tree branches above a branching point at any height is equal to the cross-sectional area of the trunk or the branch immediately below the branching point) using simulations based on two biomechanical models: the uniform stress and elastic similarity models. Model calculations of the daughter/mother ratio (i.e., the ratio of the total cross-sectional area of the daughter branches to the cross-sectional area of the mother branch at the branching point) showed that both biomechanical models agreed with da Vinci's rule when the branching angles of daughter branches and the weights of lateral daughter branches were small; however, the models deviated from da Vinci's rule as the weights and/or the branching angles of lateral daughter branches increased. The calculated values of the two models were largely similar but differed in some ways. Field measurements of Fagus crenata and Abies homolepis also fit this trend, wherein models deviated from da Vinci's rule with increasing relative weights of lateral daughter branches. However, this deviation was small for a branching pattern in nature, where empirical measurements were taken under realistic measurement conditions; thus, da Vinci's rule did not critically contradict the biomechanical models in the case of real branching patterns, though the model calculations described the contradiction between da Vinci's rule and the biomechanical models. The field data for Fagus crenata fit the uniform stress model best, indicating that stress uniformity is the key constraint of branch morphology in Fagus crenata rather than elastic similarity or da Vinci's rule. On the other hand, mechanical constraints are not necessarily significant in the morphology of Abies homolepis branches, depending on the number of daughter branches. Rather, these branches were often in agreement with da Vinci's rule. PMID:24714065

Peptide-based Antibodies against Glutathione-binding Domains Suppress Superoxide Production Mediated by Mitochondrial Complex I*

PubMed Central

Chen, Jingfeng; Chen, Chwen-Lih; Rawale, Sharad; Chen, Chun-An; Zweier, Jay L.; Kaumaya, Pravin T. P.; Chen, Yeong-Renn

2010-01-01

Complex I (NQR) is a critical site of superoxide () production and the major host of redox protein thiols in mitochondria. In response to oxidative stress, NQR-derived protein thiols at the 51- and 75-kDa subunits are known to be reversibly S-glutathionylated. Although several glutathionylated domains from NQR 51 and 75 kDa have been identified, their roles in the regulatory functions remain to be explored. To gain further insights into protein S-glutathionylation of complex I, we used two peptides of S-glutathionylated domain (200GAGAYICGEETALIESIEGK219 of 51-kDa protein and 361VDSDTLCTEEVFPTAGAGTDLR382 of 75-kDa protein) as chimeric epitopes incorporating a “promiscuous” T-cell epitope to generate two polyclonal antibodies, AbGSCA206 and AbGSCB367. Binding of AbGSCA206 and AbGSCB367 inhibited NQR-mediated generation by 37 and 57%, as measured by EPR spin-trapping. To further provide an appropriate control, two peptides of non-glutathionylated domain (21SGDTTAPKKTSFGSLKDFDR40 of 51-kDa peptide and 100WNILTNSEKTKKAREGVMEFL120 of 75-kDa peptide) were synthesized as chimeric epitopes to generate two polyclonal antibodies, Ab51 and Ab75. Binding of A51 did not affect NQR-mediated generation to a significant level. However, binding of Ab75 inhibited NQR-mediated generation by 35%. None of AbGSCA206, AbGSCB367, Ab51, or Ab75 showed an inhibitory effect on the electron transfer activity of NQR, suggesting that antibody binding to the glutathione-binding domain decreased electron leakage from the hydrophilic domain of NQR. When heart tissue homogenates were immunoprecipitated with Ab51 or Ab75 and probed with an antibody against glutathione, protein S-glutathionylation was enhanced in post-ischemic myocardium at the NQR 51-kDa subunit, but not at the 75-kDa subunit, indicating that the 51-kDa subunit of flavin subcomplex is more sensitive to oxidative stress resulting from myocardial infarction. PMID:19940158

Tree branching: Leonardo da Vinci's rule versus biomechanical models.

PubMed

Minamino, Ryoko; Tateno, Masaki

2014-01-01

This study examined Leonardo da Vinci's rule (i.e., the sum of the cross-sectional area of all tree branches above a branching point at any height is equal to the cross-sectional area of the trunk or the branch immediately below the branching point) using simulations based on two biomechanical models: the uniform stress and elastic similarity models. Model calculations of the daughter/mother ratio (i.e., the ratio of the total cross-sectional area of the daughter branches to the cross-sectional area of the mother branch at the branching point) showed that both biomechanical models agreed with da Vinci's rule when the branching angles of daughter branches and the weights of lateral daughter branches were small; however, the models deviated from da Vinci's rule as the weights and/or the branching angles of lateral daughter branches increased. The calculated values of the two models were largely similar but differed in some ways. Field measurements of Fagus crenata and Abies homolepis also fit this trend, wherein models deviated from da Vinci's rule with increasing relative weights of lateral daughter branches. However, this deviation was small for a branching pattern in nature, where empirical measurements were taken under realistic measurement conditions; thus, da Vinci's rule did not critically contradict the biomechanical models in the case of real branching patterns, though the model calculations described the contradiction between da Vinci's rule and the biomechanical models. The field data for Fagus crenata fit the uniform stress model best, indicating that stress uniformity is the key constraint of branch morphology in Fagus crenata rather than elastic similarity or da Vinci's rule. On the other hand, mechanical constraints are not necessarily significant in the morphology of Abies homolepis branches, depending on the number of daughter branches. Rather, these branches were often in agreement with da Vinci's rule.

Exploring the Prevalence of Disrespect and Abuse during Childbirth in Kenya

PubMed Central

Abuya, Timothy; Warren, Charlotte E.; Miller, Nora; Njuki, Rebecca; Ndwiga, Charity; Maranga, Alice; Mbehero, Faith; Njeru, Anne; Bellows, Ben

2015-01-01

Background Poor quality of care including fear of disrespect and abuse (D&A) perpetuated by health workers influences women’s decisions to seek maternity care. Key manifestations of D&A include: physical abuse, non-consented care, non-confidential care, non-dignified care, discrimination, abandonment, and detention in facilities. This paper describes manifestations of D&A experienced in Kenya and measures their prevalence. Methods This paper is based on baseline data collected during a before-and-after study designed to measure the effect of a package of interventions to reduce the prevalence of D&A experienced by women during labor and delivery in thirteen Kenyan health facilities. Data were collected through an exit survey of 641 women discharged from postnatal wards. We present percentages of D&A manifestations and odds ratios of its relationship with demographic characteristics using a multivariate fixed effects logistic regression model. Results Twenty percent of women reported any form of D&A. Manifestations of D&A includes: non-confidential care (8.5%), non-dignified care (18%), neglect or abandonment (14.3%), Non-consensual care (4.3%) physical abuse (4.2%) and, detainment for non-payment of fees (8.1). Women aged 20-29 years were less likely to experience non-confidential care compared to those under 19; OR: [0.6 95% CI (0.36, 0.90); p=0.017]. Clients with no companion during delivery were less likely to experience inappropriate demands for payment; OR: [0.49 (0.26, 0.95); p=0.037]; while women with higher parities were three times more likely to be detained for lack of payment and five times more likely to be bribed compared to those experiencing there first birth. Conclusion One out of five women experienced feeling humiliated during labor and delivery. Six categories of D&A during childbirth in Kenya were reported. Understanding the prevalence of D&A is critical in developing interventions at national, health facility and community levels to address the factors and drivers that influence D&A in facilities and to encourage clients’ future facility utilization. PMID:25884566

Exploring the prevalence of disrespect and abuse during childbirth in Kenya.

PubMed

Abuya, Timothy; Warren, Charlotte E; Miller, Nora; Njuki, Rebecca; Ndwiga, Charity; Maranga, Alice; Mbehero, Faith; Njeru, Anne; Bellows, Ben

2015-01-01

Poor quality of care including fear of disrespect and abuse (D&A) perpetuated by health workers influences women's decisions to seek maternity care. Key manifestations of D&A include: physical abuse, non-consented care, non-confidential care, non-dignified care, discrimination, abandonment, and detention in facilities. This paper describes manifestations of D&A experienced in Kenya and measures their prevalence. This paper is based on baseline data collected during a before-and-after study designed to measure the effect of a package of interventions to reduce the prevalence of D&A experienced by women during labor and delivery in thirteen Kenyan health facilities. Data were collected through an exit survey of 641 women discharged from postnatal wards. We present percentages of D&A manifestations and odds ratios of its relationship with demographic characteristics using a multivariate fixed effects logistic regression model. Twenty percent of women reported any form of D&A. Manifestations of D&A includes: non-confidential care (8.5%), non-dignified care (18%), neglect or abandonment (14.3%), Non-consensual care (4.3%) physical abuse (4.2%) and, detainment for non-payment of fees (8.1). Women aged 20-29 years were less likely to experience non-confidential care compared to those under 19; OR: [0.6 95% CI (0.36, 0.90); p=0.017]. Clients with no companion during delivery were less likely to experience inappropriate demands for payment; OR: [0.49 (0.26, 0.95); p=0.037]; while women with higher parities were three times more likely to be detained for lack of payment and five times more likely to be bribed compared to those experiencing there first birth. One out of five women experienced feeling humiliated during labor and delivery. Six categories of D&A during childbirth in Kenya were reported. Understanding the prevalence of D&A is critical in developing interventions at national, health facility and community levels to address the factors and drivers that influence D&A in facilities and to encourage clients' future facility utilization.

Percent Mammographic Density and Dense Area as Risk Factors for Breast Cancer.

PubMed

Rauh, C; Hack, C C; Häberle, L; Hein, A; Engel, A; Schrauder, M G; Fasching, P A; Jud, S M; Ekici, A B; Loehberg, C R; Meier-Meitinger, M; Ozan, S; Schulz-Wendtland, R; Uder, M; Hartmann, A; Wachter, D L; Beckmann, M W; Heusinger, K

2012-08-01

Purpose: Mammographic characteristics are known to be correlated to breast cancer risk. Percent mammographic density (PMD), as assessed by computer-assisted methods, is an established risk factor for breast cancer. Along with this assessment the absolute dense area (DA) of the breast is reported as well. Aim of this study was to assess the predictive value of DA concerning breast cancer risk in addition to other risk factors and in addition to PMD. Methods: We conducted a case control study with hospital-based patients with a diagnosis of invasive breast cancer and healthy women as controls. A total of 561 patients and 376 controls with available mammographic density were included into this study. We describe the differences concerning the common risk factors BMI, parital status, use of hormone replacement therapy (HRT) and menopause between cases and controls and estimate the odds ratios for PMD and DA, adjusted for the mentioned risk factors. Furthermore we compare the prediction models with each other to find out whether the addition of DA improves the model. Results: Mammographic density and DA were highly correlated with each other. Both variables were as well correlated to the commonly known risk factors with an expected direction and strength, however PMD (ρ = -0.56) was stronger correlated to BMI than DA (ρ = -0.11). The group of women within the highest quartil of PMD had an OR of 2.12 (95 % CI: 1.25-3.62). This could not be seen for the fourth quartile concerning DA. However the assessment of breast cancer risk could be improved by including DA in a prediction model in addition to common risk factors and PMD. Conclusions: The inclusion of the parameter DA into a prediction model for breast cancer in addition to established risk factors and PMD could improve the breast cancer risk assessment. As DA is measured together with PMD in the process of computer-assisted assessment of PMD it might be considered to include it as one additional breast cancer risk factor that is obtained from breast imaging.

Dopamine fluorescent sensors based on polypyrrole/graphene quantum dots core/shell hybrids.

PubMed

Zhou, Xi; Ma, Peipei; Wang, Anqi; Yu, Chenfei; Qian, Tao; Wu, Shishan; Shen, Jian

2015-02-15

A facilely prepared fluorescent sensor was developed for dopamine (DA) detection with high sensitivity and selectivity based on polypyrrole/graphene quantum dots (PPy/GQDs) core/shell hybrids. The composites exhibit strong fluorescence emission, which is dramatically enhanced as high as three times than pristine GQDs. The prepared sensor allows a highly sensitive determination of DA by fluorescent intensity decreasing with the addition of DA and presents a good linearity in range of 5-8000 nM with the detection limit of 10 pM (S/N = 3). Furthermore, the application of the proposed approach have been demonstrated in real samples and showed promise in diagnostic purposes. Copyright © 2014 Elsevier B.V. All rights reserved.

An efficient optical-electrochemical dual probe for highly sensitive recognition of dopamine based on terbium complex functionalized reduced graphene oxide.

PubMed

Zhou, Zhan; Wang, Qianming

2014-05-07

A novel organic-inorganic hybrid sensor based on diethylenetriaminepentaacetic acid (DTPA) modified reduced graphene oxide (RGO-DTPA) chelated with terbium ions allows detection of dopamine (DA) through an emission enhancement effect. Its luminescence, peaking at 545 nm, has been improved by a factor of 25 in the presence of DA (detection limit = 80 nM). In addition, this covalently bonded terbium complex functionalized reduced graphene oxide (RGO-DTPA-Tb) can be successfully assembled on a glassy carbon electrode. The assay performed through differential pulse voltammetry (DPV) yielded obvious peak separation between DA and excessive amounts of the interfering ascorbic acid (AA).

Evaluation of a Decision Aid for Women with Epilepsy Who Are Considering Pregnancy: A Randomized Controlled Trial.

PubMed

McGrath, Amanda; Sharpe, Louise; Lah, Suncica; Parratt, Kaitlyn

2017-07-01

For many women with epilepsy (WWE), decision making about pregnancy is complicated by considerations such as the potential teratogenicity of antiepileptic drugs, offspring risk of epilepsy, seizure occurrence during pregnancy, and the challenges of parenting amidst poorly controlled seizures. This proof-of-concept, randomized controlled trial aimed to evaluate a decision aid (DA) developed to help WWE decide if they should start or enlarge their families. Seventy-nine WWE of childbearing age were recruited from Epilepsy Action Australia between October and November 2013 and randomized to receive the intervention (the DA) or not, and to complete a set of questionnaires pre- and post- intervention. The DA, delivered as a PDF booklet, provided balanced evidence-based information about options, risks and benefits, including probabilities; as well as steps for clarifying values and considering options within one's personal situation. Compared with the control group, the DA group had statistically significant improvements in knowledge about pregnancy and epilepsy (Cohen's d = 1.24; 95%CI = 0.77 to 1.83) and reduced decisional conflict (Cohen's d = 0.59; 95%CI = 0.21 to 0.99). Changes in decision self-efficacy, certainty of choice, patient-practitioner communication abilities and value congruence with choice were comparable between the DA and control group. Importantly, women's decisions about motherhood were not biased towards either direction, and there were no adverse effects on depression or anxiety. All women who received the DA indicated they would recommend it to other WWE. The DA has the potential to serve as a useful support tool for WWE who are considering motherhood. Future research is needed to test the DA in clinical settings with guidance from a health professional. The trial was registered with the Australian New Zealand Clinical Trials Registry (ID ACTRN12613001082796).

Study protocol for promoting respectful maternity care initiative to assess, measure and design interventions to reduce disrespect and abuse during childbirth in Kenya

PubMed Central

2013-01-01

Background Increases in the proportion of facility-based deliveries have been marginal in many low-income countries in the African region. Preliminary clinical and anthropological evidence suggests that one major factor inhibiting pregnant women from delivering at facility is disrespectful and abusive treatment by health care providers in maternity units. Despite acknowledgement of this behavior by policy makers, program staff, civil society groups and community members, the problem appears to be widespread but prevalence is not well documented. Formative research will be undertaken to test the reliability and validity of a disrespect and abuse (D&A) construct and to then measure the prevalence of disrespect and abuse suffered by clinic clients and the general population. Methods/design A quasi-experimental design will be followed with surveys at twelve health facilities in four districts and one large maternity hospital in Nairobi and areas before and after the introduction of disrespect and abuse (D&A) interventions. The design is aimed to control for potential time dependent confounding on observed factors. Discussion This study seeks to conduct implementation research aimed at designing, testing, and evaluating an approach to significantly reduce disrespectful and abusive (D&A) care of women during labor and delivery in facilities. Specifically the proposed study aims to: (i) determine the manifestations, types and prevalence of D&A in childbirth (ii) develop and validate tools for assessing D&A (iii) identify and explore the potential drivers of D&A (iv) design, implement, monitor and evaluate the impact of one or more interventions to reduce D&A and (v) document and assess the dynamics of implementing interventions to reduce D&A and generate lessons for replication at scale. PMID:23347548

Complexity of VTA DA neural activities in response to PFC transection in nicotine treated rats.

PubMed

Chen, Ting Y; Zhang, Die; Dragomir, Andrei; Akay, Yasemin M; Akay, Metin

2011-02-27

The dopaminergic (DA) neurons in the ventral tegmental area (VTA) are widely implicated in the addiction and natural reward circuitry of the brain. These neurons project to several areas of the brain, including prefrontal cortex (PFC), nucleus accubens (NAc) and amygdala. The functional coupling between PFC and VTA has been demonstrated, but little is known about how PFC mediates nicotinic modulation in VTA DA neurons. The objectives of this study were to investigate the effect of acute nicotine exposure on the VTA DA neuronal firing and to understand how the disruption of communication from PFC affects the firing patterns of VTA DA neurons. Extracellular single-unit recordings were performed on Sprague-Dawley rats and nicotine was administered after stable recording was established as baseline. In order to test how input from PFC affects the VTA DA neuronal firing, bilateral transections were made immediate caudal to PFC to mechanically delete the interaction between VTA and PFC. The complexity of the recorded neural firing was subsequently assessed using a method based on the Lempel-Ziv estimator. The results were compared with those obtained when computing the entropy of neural firing. Exposure to nicotine triggered a significant increase in VTA DA neurons firing complexity when communication between PFC and VTA was present, while transection obliterated the effect of nicotine. Similar results were obtained when entropy values were estimated. Our findings suggest that PFC plays a vital role in mediating VTA activity. We speculate that increased firing complexity with acute nicotine administration in PFC intact subjects is due to the close functional coupling between PFC and VTA. This hypothesis is supported by the fact that deletion of PFC results in minor alterations of VTA DA neural firing when nicotine is acutely administered.

The Effect of Antibody Size and Mechanical Loading on Solute Diffusion Through the Articular Surface of Cartilage.

PubMed

DiDomenico, Chris D; Goodearl, Andrew; Yarilina, Anna; Sun, Victor; Mitra, Soumya; Sterman, Annette Schwartz; Bonassar, Lawrence J

2017-09-01

Because of the heterogeneous nature of articular cartilage tissue, penetration of potential therapeutic molecules for osteoarthritis (OA) through the articular surface (AS) is complex, with many factors that affect transport of these solutes within the tissue. Therefore, the goal of this study is to investigate how the size of antibody (Ab) variants, as well as application of cyclic mechanical loading, affects solute transport within healthy cartilage tissue. Penetration of fluorescently tagged solutes was quantified using confocal microscopy. For all the solutes tested, fluorescence curves were obtained through the articular surface. On average, diffusivities for the solutes of sizes 200 kDa, 150 kDa, 50 kDa, and 25 kDa were 3.3, 3.4, 5.1, and 6.0 μm2/s from 0 to 100 μm from the articular surface. Diffusivities went up to a maximum of 16.5, 18.5, 20.5, and 23.4 μm2/s for the 200 kDa, 150 kDa, 50 kDa, and 25 kDa molecules, respectively, from 225 to 325 μm from the surface. Overall, the effect of loading was very significant, with maximal transport enhancement for each solute ranging from 2.2 to 3.4-fold near 275 μm. Ultimately, solutes of this size do not diffuse uniformly nor are convected uniformly, through the depth of the cartilage tissue. This research potentially holds great clinical significance to discover ways of further optimizing transport into cartilage and leads to effective antibody-based treatments for OA.

Nuclear 82-kDa choline acetyltransferase decreases amyloidogenic APP metabolism in neurons from APP/PS1 transgenic mice.

PubMed

Albers, Shawn; Inthathirath, Fatima; Gill, Sandeep K; Winick-Ng, Warren; Jaworski, Ewa; Wong, Daisy Y L; Gros, Robert; Rylett, R Jane

2014-09-01

Alzheimer disease (AD) is associated with increased amyloidogenic processing of amyloid precursor protein (APP) to β-amyloid peptides (Aβ), cholinergic neuron loss with decreased choline acetyltransferase (ChAT) activity, and cognitive dysfunction. Both 69-kDa ChAT and 82-kDa ChAT are expressed in cholinergic neurons in human brain and spinal cord with 82-kDa ChAT localized predominantly to neuronal nuclei, suggesting potential alternative functional roles for the enzyme. By gene microarray analysis, we found that 82-kDa ChAT-expressing IMR32 neural cells have altered expression of genes involved in diverse cellular functions. Importantly, genes for several proteins that regulate APP processing along amyloidogenic and non-amyloidogenic pathways are differentially expressed in 82-kDa ChAT-containing cells. The predicted net effect based on observed changes in expression patterns of these genes would be decreased amyloidogenic APP processing with decreased Aβ production. This functional outcome was verified experimentally as a significant decrease in BACE1 protein levels and activity and a concomitant reduction in the release of endogenous Aβ1-42 from neurons cultured from brains of AD-model APP/PS1 transgenic mice. The expression of 82-kDa ChAT in neurons increased levels of GGA3, which is involved in trafficking BACE1 to lysosomes for degradation. shRNA-induced decreases in GGA3 protein levels attenuated the 82-kDa ChAT-mediated decreases in BACE1 protein and activity and Aβ1-42 release. Evidence that 82-kDa ChAT can enhance GGA3 gene expression is shown by enhanced GGA3 gene promoter activity in SN56 neural cells expressing this ChAT protein. These studies indicate a novel relationship between cholinergic neurons and APP processing, with 82-kDa ChAT acting as a negative regulator of Aβ production. This decreased formation of Aβ could result in protection for cholinergic neurons, as well as protection of other cells in the vicinity that are sensitive to increased levels of Aβ. Decreasing levels of 82-kDa ChAT due to increasing age or neurodegeneration could alter the balance towards increasing Aβ production, with this potentiating the decline in function of cholinergic neurons. Copyright © 2014 Elsevier Inc. All rights reserved.

Central dopaminergic neurotransmission plays an important role in thermoregulation and performance during endurance exercise.

PubMed

Zheng, Xinyan; Hasegawa, Hiroshi

2016-10-01

Dopamine (DA) has been widely investigated for its potential role in determining exercise performance. It was originally thought that DA's ergogenic effect was by mediating psychological responses. Recently, some studies have also suggested that DA may regulate physiological responses, such as thermoregulation. Hyperthermia has been demonstrated as an important limiting factor during endurance exercise. DA is prominent in the thermoregulatory centre, and changes in DA concentration have been shown to affect core temperature regulation during exercise. Some studies have proposed that DA or DA/noradrenaline (NA) reuptake inhibitors can improve exercise performance, despite hyperthermia during exercise in the heat. DA/NA reuptake inhibitors also increase catecholamine release in the thermoregulatory centre. Intracerebroventricularly injected DA has been shown to improve exercise performance through inhibiting hyperthermia-induced fatigue, even at normal ambient temperatures. Further, caffeine has been reported to increase DA release in the thermoregulatory centre and improves endurance exercise performance despite increased core body temperature. Taken together, DA has been shown to have ergogenic effects and increase heat storage and hyperthermia tolerance. The mechanisms underlying these effects seem to involve limiting/overriding the inhibitory signals from the central nervous system that result in cessation of exercise due to hyperthermia.

Novel codrugs with GABAergic activity for dopamine delivery in the brain.

PubMed

Denora, Nunzio; Cassano, Tommaso; Laquintana, Valentino; Lopalco, Antonio; Trapani, Adriana; Cimmino, Concetta Stefania; Laconca, Leonardo; Giuffrida, Andrea; Trapani, Giuseppe

2012-11-01

This study investigates the use of codrugs of the GABAergic agent 2-phenyl-imidazo[1,2-a]pyridinacetamide and dopamine (DA) or ethyl ester L-Dopa (LD) as a strategy to deliver DA and simultaneously activate GABA-receptors in the brain. For this purpose, both DA and LD ethyl ester were linked by carbamate bond to imidazo[1,2-a]pyridine acetamide moieties to yield two DA- and two LD-imidazopyridine derivatives. These compounds were evaluated in vitro to assess their stability, binding affinities and cell membrane transport, and in vivo to assess their bio-availability via microdialysis studies. The two DA derivatives were adequately stable in buffered solution, but underwent cleavage in diluted human serum. By contrast, the LD derivatives were unstable in buffered solution. Receptor binding studies showed that the DA-imidazopyridine carbamates had binding affinity for benzodiazepine receptors in the nanomolar range. Brain microdialysis experiments indicated that intraperitoneal administration of the DA derivatives sustained DA levels in rat striatum over a 4-h period. These results suggest that DA-imidazopyridine carbamates are new DA codrugs with potential application for DA replacement therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

Monitoring Domoic Acid production by Solid Phase Adsorption Toxin Tracking off the Santa Cruz Municipal Warf, Santa Cruz, California

NASA Astrophysics Data System (ADS)

Nolan, M.; Ziccarelli, L.; Kudela, R. M.

2013-12-01

Certain species of the diatom genus Pseudo-nitzschia are producers of the neurotoxin, domoic acid (DA). DA is known to cause amnesic shellfish poisoning also known as domoic acid poisoning, which can lead to permanent brain damage in humans and marine mammals. DA accumulates at higher trophic levels, generally due to consumption of toxic cells or through trophic transfer, and can potentially cause death of both humans and marine wildlife. The Santa Cruz Municipal Warf experiences periodic rises in DA concentrations, which can reach toxic levels in shellfish, fish, and other marine organisms. While these increases in toxicity often occur during Pseudo-nitzschia blooms, several periods of elevated DA have occurred when diatom abundance is restricted and/or dominated by non-toxic species, and there is increasing evidence that DA dissolved in seawater may be prevalent. One theory suggests that senescent or dead Pseudo-nitzschia cells sink to the benthos while retaining their toxin and are buried in sediment following the death of a bloom. Therefore, DA may accumulate in the benthos, where it is eventually released during storms or wave and tide conditions that disturb the sediment. We sampled DA in situ using Solid Phase Adsorption Toxin Tracking (SPATT) bags SPATT uses a synthetic resin to capture dissolved DA, allowing for the determination of integrated DA concentrations at known time intervals. The alternative method is mussel biotoxin monitoring, but it is less accurate due to uncertainties in the time of DA accumulation within the mussel, and the lack of uptake of dissolved DA by the mussel. We deployed and collected SPATT off the Santa Cruz Municipal Wharf at multiple depths beginning in February 2013. We expect to see increasing DA following the death of a harmful algal bloom. Under pre-bloom conditions, little to no DA has been detected in mussels or surface SPATT, but DA from SPATT is frequently observed at depth, suggesting that the sediment is exposed to (or acts as a reservoir for) DA, and that benthic organisms are chronically exposed to DA.

Anti-MRSA malleable liposomes carrying chloramphenicol for ameliorating hair follicle targeting.

PubMed

Hsu, Ching-Yun; Yang, Shih-Chun; Sung, Calvin T; Weng, Yi-Han; Fang, Jia-You

2017-01-01

Pathogens usually invade hair follicles when skin infection occurs. The accumulated bacteria in follicles are difficult to eradicate. The present study aimed to assess the cutaneous and follicular delivery of chloramphenicol (Cm)-loaded liposomes and the antibacterial activity of these liposomes against methicillin-resistant Staphylococcus aureus (MRSA). Skin permeation was conducted by in vitro Franz diffusion cell. The anti-MRSA potential was checked using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), a well diffusion test, and intracellular MRSA killing. The classic, dimyristoylphosphatidylcholine (DMPC), and deoxycholic acid (DA) liposomes had a vesicle size of 98, 132, and 239 nm, respectively. The incorporation of DMPC or DA into the liposomes increased the bilayer fluidity. The malleable vesicles containing DMPC and DA showed increased follicular Cm uptake over the control solution by 1.5- and 2-fold, respectively. The MIC and MBC of DA liposomes loaded with Cm were 62.5 and 62.5-125 μg/mL, comparable to free Cm. An inhibition zone about 2-fold higher was achieved by DA liposomes as compared to the free control at a Cm dose of 0.5 mg/mL. DA liposomes also augmented antibacterial activity on keratinocyte-infected MRSA. The deformable liposomes had good biocompatibility against keratinocytes and neutrophils (viability >80%). In vivo administration demonstrated that DA liposomes caused negligible toxicity on the skin, based on physiological examination and histology. These data suggest the potential application of malleable liposomes for follicular targeting and the treatment of MRSA-infected dermatologic conditions.

Bioinspired Synthesis of Photocatalytic Nanocomposite Membranes Based on Synergy of Au-TiO2 and Polydopamine for Degradation of Tetracycline under Visible Light.

PubMed

Wang, Chen; Wu, Yilin; Lu, Jian; Zhao, Juan; Cui, Jiuyun; Wu, Xiuling; Yan, Yongsheng; Huo, Pengwei

2017-07-19

A bioinspired photocatalytic nanocomposite membrane was successfully prepared via polydopamine (pDA)-coated poly(vinylidene fluoride) (PVDF) membrane, as a secondary platform for vacuum-filtrated Au-TiO 2 nanocomposites, with enhanced photocatalytic activity. The degradation efficiency of Au-TiO 2 /pDA/PVDF membranes reached 92% when exposed to visible light for 120 min, and the degradation efficiency of Au-TiO 2 /pDA/PVDF membranes increased by 26% compared to that of Au-TiO 2 powder and increased by 51% compared to that of TiO 2 /pDA/PVDF nanocomposite membranes. The degradation efficiency remained about 90% after five cycle experiments, and the Au-TiO 2 /pDA/PVDF nanocomposite membranes showed good stability, regeneration performance, and easy recycling. The pDA coating not only served as a bioadhesion interface to improve the bonding force between the catalyst and the membrane substrate but also acted as a photosensitizer to broaden the wavelength response range of TiO 2 , and the structure of Au-TiO 2 /pDA/PVDF also improves the transfer rate of photogenerated electrons; the surface plasmon resonance effect of Au also played a positive role in improving the activity of the catalyst. Therefore, we believe that this study opens up a new strategy in preparing the bioinspired photocatalytic nanocomposite membrane for potential wastewater purification, catalysis, and as a membrane separation field.

Investigation of the reduction process of dopamine using paired pulse voltammetry

PubMed Central

Kim, Do Hyoung; Oh, Yoonbae; Shin, Hojin; Blaha, Charles D.; Bennet, Kevin E.; Lee, Kendall H.; Kim, In Young; Jang, Dong Pyo

2014-01-01

The oxidation of dopamine (DA) around +0.6V potential in anodic sweep and its reduction around −0.1V in cathodic sweep at a relatively fast scanning rate (300 V/s or greater) have been used for identification of DA oxidation in fast-scan cyclic voltammetry (FSCV). However, compared to the oxidation peak of DA, the reduction peak has not been fully examined in analytical studies, although it has been used as one of the representative features to identify DA. In this study, the reduction process of DA was investigated using paired pulse voltammetry (PPV), which consists of two identical triangle-shaped waveforms, separated by a short interval at the holding potential. Especially, the discrepancies between the magnitude of the oxidation and reduction peaks of DA were investigated based on three factors: (1) the instant desorption of the DA oxidation product (dopamine-o-quinone: DOQ) after production, (2) the effect of the holding potential on the reduction process, and (3) the rate-limited reduction process of DA. For the first test, the triangle waveform FSCV experiment was performed on DA with various scanrates (from 400 to 1000 V/s) and durations of switching potentials of the triangle waveform (from 0.0 to 6.0 ms) in order to vary the duration between the applied oxidation potential at +0.6V and the reduction potential at −0.2V. As a result, the ratio of reduction over oxidation peak current response decreased as the duration became longer. To evaluate the effect of holding potentials during the reduction process, FSCV experiments were conducted with holding potential from 0.0V to −0.8V. We found that more negative holding potentials lead to larger amount of reduction process. For evaluation of the rate-limited reduction process of DA, PPV with a 1Hz repetition rate and various delays (2, 8, 20, 40 and 80ms) between the paired scans were utilized to determine how much reduction process occurred during the holding potential (−0.4V). These tests showed that relatively large amounts of DOQ are reduced to DA during the holding potential. The rate-limited reduction process was also confirmed with the increase of reduction in a lower pH environment. In addition to the mechanism of the reduction process of DA, we found that the differences between the responses of primary and secondary pulses in PPV were mainly dependent on the rate-limited reduction process during the holding potential. In conclusion, the reduction process may be one of the important factors to be considered in the kinetic analysis of DA and other electroactive species in brain tissue and in the design of new types of waveform in FSCV. PMID:24926227

Dextral strike-slip along the Kapıdağ shear zone (NW Turkey): evidence for Eocene westward translation of the Anatolian plate

NASA Astrophysics Data System (ADS)

Türkoğlu, Ercan; Zulauf, Gernold; Linckens, Jolien; Ustaömer, Timur

2016-10-01

The northern part of the Kapıdağ Peninsula (Marmara Sea, NW Turkey) is affected by the E-W trending Kapıdağ shear zone, which cuts through calc-alkaline granitoids of the Ocaklar pluton resulting in mylonitic orthogneiss. Macroscopic and microscopic shear-sense indicators, such as SC fabrics, shear bands, σ-clasts and mica fish, unequivocally suggest dextral strike-slip for the Kapıdağ shear zone. Based on petrographic data, deformation microfabrics of quartz and feldspar, and the slip systems in quartz, the dextral shearing should have been active at T = 500-300 °C and P < 5 kbar. Published K-Ar and 39Ar-40Ar cooling ages of hornblende and biotite suggest that cooling below 500-300 °C occurred during the Eocene (ca. 45-ca. 35 Ma), meaning that the Kapıdağ shear zone should have been active during Middle to Late Eocene times. The differential stress related to the shearing was <50 MPa as is indicated by the size of recrystallized quartz grains. Based on the new and published data, it is concluded that the westward movement of the Anatolian plate might have been active almost continuously from the Middle Eocene until recent times.

Virtual-source diffusion approximation for enhanced near-field modeling of photon-migration in low-albedo medium.

PubMed

Jia, Mengyu; Chen, Xueying; Zhao, Huijuan; Cui, Shanshan; Liu, Ming; Liu, Lingling; Gao, Feng

2015-01-26

Most analytical methods for describing light propagation in turbid medium exhibit low effectiveness in the near-field of a collimated source. Motivated by the Charge Simulation Method in electromagnetic theory as well as the established discrete source based modeling, we herein report on an improved explicit model for a semi-infinite geometry, referred to as "Virtual Source" (VS) diffuse approximation (DA), to fit for low-albedo medium and short source-detector separation. In this model, the collimated light in the standard DA is analogously approximated as multiple isotropic point sources (VS) distributed along the incident direction. For performance enhancement, a fitting procedure between the calculated and realistic reflectances is adopted in the near-field to optimize the VS parameters (intensities and locations). To be practically applicable, an explicit 2VS-DA model is established based on close-form derivations of the VS parameters for the typical ranges of the optical parameters. This parameterized scheme is proved to inherit the mathematical simplicity of the DA approximation while considerably extending its validity in modeling the near-field photon migration in low-albedo medium. The superiority of the proposed VS-DA method to the established ones is demonstrated in comparison with Monte-Carlo simulations over wide ranges of the source-detector separation and the medium optical properties.

The pharmacology of effort-related choice behavior: Dopamine, depression, and individual differences.

PubMed

Salamone, John D; Correa, Merce; Yohn, Samantha; Lopez Cruz, Laura; San Miguel, Noemi; Alatorre, Luisa

2016-06-01

This review paper is focused upon the involvement of mesolimbic dopamine (DA) and related brain systems in effort-based processes. Interference with DA transmission affects instrumental behavior in a manner that interacts with the response requirements of the task, such that rats with impaired DA transmission show a heightened sensitivity to ratio requirements. Impaired DA transmission also affects effort-related choice behavior, which is assessed by tasks that offer a choice between a preferred reinforcer that has a high work requirement vs. less preferred reinforcer that can be obtained with minimal effort. Rats and mice with impaired DA transmission reallocate instrumental behavior away from food-reinforced tasks with high response costs, and show increased selection of low reinforcement/low cost options. Tests of effort-related choice have been developed into models of pathological symptoms of motivation that are seen in disorders such as depression and schizophrenia. These models are being employed to explore the effects of conditions associated with various psychopathologies, and to assess drugs for their potential utility as treatments for effort-related symptoms. Studies of the pharmacology of effort-based choice may contribute to the development of treatments for symptoms such as psychomotor slowing, fatigue or anergia, which are seen in depression and other disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

A-DaGO-Fun: an adaptable Gene Ontology semantic similarity-based functional analysis tool.

PubMed

Mazandu, Gaston K; Chimusa, Emile R; Mbiyavanga, Mamana; Mulder, Nicola J

2016-02-01

Gene Ontology (GO) semantic similarity measures are being used for biological knowledge discovery based on GO annotations by integrating biological information contained in the GO structure into data analyses. To empower users to quickly compute, manipulate and explore these measures, we introduce A-DaGO-Fun (ADaptable Gene Ontology semantic similarity-based Functional analysis). It is a portable software package integrating all known GO information content-based semantic similarity measures and relevant biological applications associated with these measures. A-DaGO-Fun has the advantage not only of handling datasets from the current high-throughput genome-wide applications, but also allowing users to choose the most relevant semantic similarity approach for their biological applications and to adapt a given module to their needs. A-DaGO-Fun is freely available to the research community at http://web.cbio.uct.ac.za/ITGOM/adagofun. It is implemented in Linux using Python under free software (GNU General Public Licence). gmazandu@cbio.uct.ac.za or Nicola.Mulder@uct.ac.za Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Lesion of medial prefrontal dopamine terminals abolishes habituation of accumbens shell dopamine responsiveness to taste stimuli.

PubMed

Bimpisidis, Zisis; De Luca, Maria Antonietta; Pisanu, Augusta; Di Chiara, Gaetano

2013-02-01

Taste stimuli increase extracellular dopamine (DA) in the nucleus accumbens (NAc) and in the medial prefrontal cortex (mPFC). This effect shows single-trial habituation in NAc shell but not in core or in mPFC. Morphine sensitization abolishes habituation of DA responsiveness in NAc shell but induces it in mPFC. These observations support the hypothesis of an inhibitory influence of mPFC DA on NAc DA. To test this hypothesis, we used in vivo microdialysis to investigate the effect of mPFC 6-hydroxy-dopamine (6-OHDA) lesions on the NAc DA responsiveness to taste stimuli. 6-OHDA was infused bilaterally in the mPFC of rats implanted with guide cannulae. After 1 week, rats were implanted with an intraoral catheter, microdialysis probes were inserted into the guide cannulae, and dialysate DA was monitored in NAc shell/core after intraoral chocolate. 6-OHDA infusion reduced tissue DA in the mPFC by 75%. Tyrosine hydroxylase immunohistochemistry showed that lesions were confined to the mPFC. mPFC 6-OHDA lesion did not affect the NAc shell DA responsiveness to chocolate in naive rats but abolished habituation in rats pre-exposed to the taste. In the NAc core, mPFC lesion potentiated, delayed and prolonged the stimulatory DA response to taste but failed to affect DA in pre-exposed rats. Behavioural taste reactions and motor activity were not affected. The results indicate a top-down control of NAc DA by mPFC and a reciprocal relationship between DA transmission in these two areas. Moreover, habituation of DA responsiveness in the NAc shell is dependent upon an intact DA input to the mPFC. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Complicated function of dopamine in Aβ-related neurotoxicity: Dual interactions with Tyr10 and SNK(26-28) of Aβ.

PubMed

Liu, Mengmeng; Kou, Lu; Bin, Yannan; Wan, Liping; Xiang, Juan

2016-11-01

With the capability to inhibit the formation of amyloid β peptides (Aβ) fibril, dopamine (DA) and other catechol derivatives have been considered for the potential treatment of Alzheimer's disease (AD). Such treatment, however, remains debatable because of the diverse functions of Aβ and DA in AD pathology. Moreover, the complicated oxidation accompanying DA has caused the majority of the previous research to focus on the binding of DA oxides onto Aβ. The molecular mechanism by which Aβ interacts with the reduction state of DA, which is correlative with the brain function, should be urgently explored. By controlling rigorous anaerobic experimental conditions, this work investigated the molecular mechanism of the Aβ/DA interaction, and two binding sites were revealed. For the binding of DA, Tyrosine (Tyr 10 ) was identified as the strong binding site, and serine-asparagine-lysing (SNK(26-28)) segment was the weak binding segment. Furthermore, the Thioflavin T (THT) fluorescence confirmed DA's positive function of inhibiting Aβ aggregation through its weakly binding with SNK(26-28) segment. Meanwhile, 7-OHCCA fluorescence exhibited DA's negative function of enhancing OH generation through inhibiting the Aβ/Cu 2+ coordination. The viability tests of the neuroblastoma SH-SY5Y cells displayed that the coexistence of DA, Cu 2+ , and Aβ induced lower cell viability than free Cu 2+ , indicating the significant negative effect of excessive DA on AD progression. This research revealed the potential DA-induced damage in AD brain, which is significant for understanding the function of DA in AD neuropathology and for designing a DA-related therapeutic strategy for AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Intranasal administration of dopamine attenuates unconditioned fear in that it reduces restraint-induced ultrasound vocalizations and escape from bright light.

PubMed

Talbot, Teddy; Mattern, Claudia; de Souza Silva, Maria Angelica; Brandão, Marcus Lira

2017-06-01

Although substantial evidence suggests that dopamine (DA) enhances conditioned fear responses, few studies have examined the role of DA in unconditioned fear states. Whereas DA does not cross the blood-brain barrier, intranasally-applied dopamine reaches the brain directly via the nose-brain pathways in rodents, providing an alternative means of targeting DA receptors. Intranasal dopamine (IN-DA) has been demonstrated to bind to DA transporters and to increase extracellular DA in the striatum as well as having memory-promoting effects in rats. The purpose of this study was to examine the influence of IN-DA in three tests of fear/anxiety. The three doses of DA hydrochloride (0.03, 0.3, or 1 mg/kg) were applied in a viscous castor oil gel in a volume of 5 µl to each of both nostrils of adult Wistar rats prior to testing of (a) escape from a bright light, using a two-chamber procedure, (b) restraint-induced 22 kHz ultrasound vocalizations (USVs), and (c) exploratory behavior in the elevated plus-maze (EPM). IN-DA dose-dependently reduced escape from bright light and the number of USV responses to restraint. It had no influence on the exploratory behavior in the EPM. IN-DA application reduced escape behavior in two tests of unconditioned fear (escape from bright light and USV response to immobilization). These findings may be interpreted in light of the known antidepressant action of IN-DA and DA reuptake blockers. The results also confirm the promise of the nasal route as an alternative means for targeting the brain's dopaminergic receptors with DA.

Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering.

PubMed

Rennerfeldt, Deena A; Renth, Amanda N; Talata, Zsolt; Gehrke, Stevin H; Detamore, Michael S

2013-11-01

Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but they can be limited in cartilage tissue engineering applications due to inadequate mechanical performance. In an effort to address this limitation, our team previously reported the drastic improvement in the mechanical performance of interpenetrating networks (IPNs) of poly(ethylene glycol) diacrylate (PEG-DA) and agarose relative to pure PEG-DA and agarose networks. The goal of the current study was specifically to determine the relative importance of PEG-DA concentration, agarose concentration, and PEG-DA molecular weight in controlling mechanical performance, swelling characteristics, and network parameters. IPNs consistently had compressive and shear moduli greater than the additive sum of either single network when compared to pure PEG-DA gels with a similar PEG-DA content. IPNs withstood a maximum stress of up to 4.0 MPa in unconfined compression, with increased PEG-DA molecular weight being the greatest contributing factor to improved failure properties. However, aside from failure properties, PEG-DA concentration was the most influential factor for the large majority of properties. Increasing the agarose and PEG-DA concentrations as well as the PEG-DA molecular weight of agarose/PEG-DA IPNs and pure PEG-DA gels improved moduli and maximum stresses by as much as an order of magnitude or greater compared to pure PEG-DA gels in our previous studies. Although the viability of encapsulated chondrocytes was not significantly affected by IPN formulation, glycosaminoglycan (GAG) content was significantly influenced, with a 12-fold increase over a three-week period in gels with a lower PEG-DA concentration. These results suggest that mechanical performance of IPNs may be tuned with partial but not complete independence from biological performance of encapsulated cells. © 2013 Elsevier Ltd. All rights reserved.

Ventricular fibrillation cardiac arrest produces a chronic striatal hyperdopaminergic state that is worsened by methylphenidate treatment.

PubMed

Nora, Gerald J; Harun, Rashed; Fine, David F; Hutchison, Daniel; Grobart, Adam C; Stezoski, Jason P; Munoz, Miranda J; Kochanek, Patrick M; Leak, Rehana K; Drabek, Tomas; Wagner, Amy K

2017-07-01

Cardiac arrest survival rates have improved with modern resuscitation techniques, but many survivors experience impairments associated with hypoxic-ischemic brain injury (HIBI). Currently, little is understood about chronic changes in striatal dopamine (DA) systems after HIBI. Given the common empiric clinical use of DA enhancing agents in neurorehabilitation, investigation evaluating dopaminergic alterations after cardiac arrest (CA) is necessary to optimize rehabilitation approaches. We hypothesized that striatal DA neurotransmission would be altered chronically after ventricular fibrillation cardiac arrest (VF-CA). Fast-scan cyclic voltammetry was used with median forebrain bundle (MFB) maximal electrical stimulations (60Hz, 10s) in rats to characterize presynaptic components of DA neurotransmission in the dorsal striatum (D-Str) and nucleus accumbens 14 days after a 5-min VF-CA when compared to Sham or Naïve. VF-CA increased D-Str-evoked overflow [DA], total [DA] released, and initial DA release rate versus controls, despite also increasing maximal velocity of DA reuptake (V max ). Methylphenidate (10 mg/kg), a DA transporter inhibitor, was administered to VF-CA and Shams after establishing a baseline, pre-drug 60 Hz, 5 s stimulation response. Methylphenidate increased initial evoked overflow [DA] more-so in VF-CA versus Sham and reduced D-Str V max in VF-CA but not Shams; these findings are consistent with upregulated striatal DA transporter in VF-CA versus Sham. Our work demonstrates that 5-min VF-CA increases electrically stimulated DA release with concomitant upregulation of DA reuptake 2 weeks after brief VF-CA insult. Future work should elucidate how CA insult duration, time after insult, and insult type influence striatal DA neurotransmission and related cognitive and motor functions. © 2017 International Society for Neurochemistry.

Web-Based Decision Aid to Assist Help-Seeking Choices for Young People Who Self-Harm: Outcomes From a Randomized Controlled Feasibility Trial.

PubMed

Rowe, Sarah L; Patel, Krisna; French, Rebecca S; Henderson, Claire; Ougrin, Dennis; Slade, Mike; Moran, Paul

2018-01-30

Adolescents who self-harm are often unsure how or where to get help. We developed a Web-based personalized decision aid (DA) designed to support young people in decision making about seeking help for their self-harm. The aim of this study was to evaluate the feasibility and acceptability of the DA intervention and the randomized controlled trial (RCT) in a school setting. We conducted a two-group, single blind, randomized controlled feasibility trial in a school setting. Participants aged 12 to 18 years who reported self-harm in the past 12 months were randomized to either a Web-based DA or to general information about mood and feelings. Feasibility of recruitment, randomization, and follow-up rates were assessed, as was acceptability of the intervention and study procedures. Descriptive data were collected on outcome measures examining decision making and help-seeking behavior. Qualitative interviews were conducted with young people, parents or carers, and staff and subjected to thematic analysis to explore their views of the DA and study processes. Parental consent was a significant barrier to young people participating in the trial, with only 17.87% (208/1164) of parents or guardians who were contacted for consent responding to study invitations. Where parental consent was obtained, we were able to recruit 81.7% (170/208) of young people into the study. Of those young people screened, 13.5% (23/170) had self-harmed in the past year. Ten participants were randomized to receiving the DA, and 13 were randomized to the control group. Four-week follow-up assessments were completed with all participants. The DA had good acceptability, but qualitative interviews suggested that a DA that addressed broader mental health problems such as depression, anxiety, and self-harm may be more beneficial. A broad-based mental health DA addressing a wide range of psychosocial problems may be useful for young people. The requirement for parental consent is a key barrier to intervention research on self-harm in the school setting. Adaptations to the research design and the intervention are needed before generalizable research about DAs can be successfully conducted in a school setting. International Standard Randomized Controlled Trial registry: ISRCTN11230559; http://www.isrctn.com/ISRCTN11230559 (Archived by WebCite at http://www.webcitation.org/6wqErsYWG). ©Sarah L Rowe, Krisna Patel, Rebecca S French, Claire Henderson, Dennis Ougrin, Mike Slade, Paul Moran. Originally published in JMIR Mental Health (http://mental.jmir.org), 30.01.2018.

Web-Based Decision Aid to Assist Help-Seeking Choices for Young People Who Self-Harm: Outcomes From a Randomized Controlled Feasibility Trial

PubMed Central

Patel, Krisna; French, Rebecca S; Henderson, Claire; Ougrin, Dennis; Slade, Mike; Moran, Paul

2018-01-01

Background Adolescents who self-harm are often unsure how or where to get help. We developed a Web-based personalized decision aid (DA) designed to support young people in decision making about seeking help for their self-harm. Objective The aim of this study was to evaluate the feasibility and acceptability of the DA intervention and the randomized controlled trial (RCT) in a school setting. Methods We conducted a two-group, single blind, randomized controlled feasibility trial in a school setting. Participants aged 12 to 18 years who reported self-harm in the past 12 months were randomized to either a Web-based DA or to general information about mood and feelings. Feasibility of recruitment, randomization, and follow-up rates were assessed, as was acceptability of the intervention and study procedures. Descriptive data were collected on outcome measures examining decision making and help-seeking behavior. Qualitative interviews were conducted with young people, parents or carers, and staff and subjected to thematic analysis to explore their views of the DA and study processes. Results Parental consent was a significant barrier to young people participating in the trial, with only 17.87% (208/1164) of parents or guardians who were contacted for consent responding to study invitations. Where parental consent was obtained, we were able to recruit 81.7% (170/208) of young people into the study. Of those young people screened, 13.5% (23/170) had self-harmed in the past year. Ten participants were randomized to receiving the DA, and 13 were randomized to the control group. Four-week follow-up assessments were completed with all participants. The DA had good acceptability, but qualitative interviews suggested that a DA that addressed broader mental health problems such as depression, anxiety, and self-harm may be more beneficial. Conclusions A broad-based mental health DA addressing a wide range of psychosocial problems may be useful for young people. The requirement for parental consent is a key barrier to intervention research on self-harm in the school setting. Adaptations to the research design and the intervention are needed before generalizable research about DAs can be successfully conducted in a school setting. Trial Registration International Standard Randomized Controlled Trial registry: ISRCTN11230559; http://www.isrctn.com/ISRCTN11230559 (Archived by WebCite at http://www.webcitation.org/6wqErsYWG) PMID:29382626

Ultrasensitive and Selective Organic FET-type Nonenzymatic Dopamine Sensor Based on Platinum Nanoparticles-Decorated Reduced Graphene Oxide.

PubMed

Oh, Jungkyun; Lee, Jun Seop; Jun, Jaemoon; Kim, Sung Gun; Jang, Jyongsik

2017-11-15

Dopamine (DA), a catecholamine hormone, is an important neurotransmitter that controls renal and cardiovascular organizations and regulates physiological activities. Abnormal concentrations of DA cause unfavorable neuronal illnesses such as Parkinson's disease, schizophrenia, and attention deficit hyperactivity disorder/attention deficit disorder. However, the DA concentration is exceedingly low in patients and difficult to detect with existing biosensors. In this study, we developed an organic field-effect-transistor-type (OFET) nonenzyme biosensor using platinum nanoparticle-decorated reduced graphene oxide (Pt_rGO) for ultrasensitive and selective DA detection. The Pt_rGOs were fabricated by reducing GO aqueous solution-containing Pt precursors (PtCl 4 ) with a chemical reducing agent. The Pt_rGOs were immobilized on a graphene substrate by π-π interactions and a conducting-polymer source-drain electrode was patterned on the substrate to form the DA sensor. The resulting OFET sensor showed a high sensitivity to remarkably low DA concentrations (100 × 10 -18 M) and selectivity among interfering molecules. Good stability was expected for the OFET sensor because it was fabricated without an enzymatic receptor, and π-π conjugation is a part of the immobilization process. Furthermore, the OFET sensors are flexible and offer the possibility of wide application as wearable and portable sensors.

A surface acoustic wave sensor functionalized with a polypyrrole molecularly imprinted polymer for selective dopamine detection.

PubMed

Maouche, Naima; Ktari, Nadia; Bakas, Idriss; Fourati, Najla; Zerrouki, Chouki; Seydou, Mahamadou; Maurel, François; Chehimi, Mohammed Mehdi

2015-11-01

A surface acoustic wave sensor operating at 104 MHz and functionalized with a polypyrrole molecularly imprinted polymer has been designed for selective detection of dopamine (DA). Optimization of pyrrole/DA ratio, polymerization and immersion times permitted to obtain a highly selective sensor, which has a sensitivity of 0.55°/mM (≈ 550 Hz/mM) and a detection limit of ≈ 10 nM. Morphology and related roughness parameters of molecularly imprinted polymer surfaces, before and after extraction of DA, as well as that of the non imprinted polymer were characterized by atomic force microscopy. The developed chemosensor selectively recognized dopamine over the structurally similar compound 4-hydroxyphenethylamine (referred as tyramine), or ascorbic acid,which co-exists with DA in body fluids at a much higher concentration. Selectivity tests were also carried out with dihydroxybenzene, for which an unexpected phase variation of order of 75% of the DA one was observed. Quantum chemical calculations, based on the density functional theory, were carried out to determine the nature of interactions between each analyte and the PPy matrix and the DA imprinted PPy polypyrrole sensing layer in order to account for the important phase variation observed during dihydroxybenzene injection. Copyright © 2015 John Wiley & Sons, Ltd.

Zeolite A functionalized with copper nanoparticles and graphene oxide for simultaneous electrochemical determination of dopamine and ascorbic acid.

PubMed

He, Ping; Wang, Wei; Du, Licheng; Dong, Faqin; Deng, Yuequan; Zhang, Tinghong

2012-08-20

A novel Cu-zeolite A/graphene modified glassy carbon electrode for the simultaneous electrochemical determination of dopamine (DA) and ascorbic acid (AA) has been described. The Cu-zeolite A/graphene composites were prepared using Cu(2+) functionalized zeolite A and graphene oxide as the precursor, and subsequently reduced by chemical agents. The composites were characterized by X-ray diffraction, Fourier transform infrared spectra and scanning electron microscopy. Based on the Cu-zeolite A/graphene-modified electrode, the potential difference between the oxidation peaks of DA and AA was over 200mV, which was adequate for the simultaneous electrochemical determination of DA and AA. Also the proposed Cu-zeolite/graphene-modified electrode showed higher electrocatalytic performance than zeolite/graphene electrode or graphene-modified electrode. The electrocatalytic oxidation currents of DA and AA were linearly related to the corresponding concentration in the range of 1.0×10(-7)-1.9×10(-5)M for DA and 2.0×10(-5)-2.0×10(-4)M for AA. Detection limits (S/N=3) were estimated to be 4.1×10(-8)M for DA and 1.1×10(-5)M for AA, respectively. Copyright © 2012 Elsevier B.V. All rights reserved.

The ATLAS PanDA Monitoring System and its Evolution

NASA Astrophysics Data System (ADS)

Klimentov, A.; Nevski, P.; Potekhin, M.; Wenaus, T.

2011-12-01

The PanDA (Production and Distributed Analysis) Workload Management System is used for ATLAS distributed production and analysis worldwide. The needs of ATLAS global computing imposed challenging requirements on the design of PanDA in areas such as scalability, robustness, automation, diagnostics, and usability for both production shifters and analysis users. Through a system-wide job database, the PanDA monitor provides a comprehensive and coherent view of the system and job execution, from high level summaries to detailed drill-down job diagnostics. It is (like the rest of PanDA) an Apache-based Python application backed by Oracle. The presentation layer is HTML code generated on the fly in the Python application which is also responsible for managing database queries. However, this approach is lacking in user interface flexibility, simplicity of communication with external systems, and ease of maintenance. A decision was therefore made to migrate the PanDA monitor server to Django Web Application Framework and apply JSON/AJAX technology in the browser front end. This allows us to greatly reduce the amount of application code, separate data preparation from presentation, leverage open source for tools such as authentication and authorization mechanisms, and provide a richer and more dynamic user experience. We describe our approach, design and initial experience with the migration process.

Gold nanoparticle based Tuberculosis immunochromatographic assay: the quantitative ESE Quanti analysis of the intensity of test and control lines.

PubMed

Mdluli, Phumlani; Tetyana, Phumlani; Sosibo, Ndabenhle; van der Walt, Hendriëtte; Mlambo, Mbuso; Skepu, Amanda; Tshikhudo, Robert

2014-04-15

A rapid dual channel lateral flow assay for the detection of Mycobacterium Tuberculosis antibodies (MTB 38 kDa monoclonal antibody) in human blood was developed. The MTB 6-14-38 kDa fusion antigen and anti-Protein A were used as the capture proteins for test and control lines respectively. Protein A labeled 40 nm gold nanoparticles were used as the detection conjugate. Whole blood and serum were spiked with MTB 38 kDa monoclonal antibody to make a positive sample model. The developed lateral flow was used to test MTB 38 kDa monoclonal antibody, and a detection limit of 5 ng/ml was used as a cut-off concentration of the analytes. The effect of the analyte concentration on the MTB lateral flow assay was studied using the variation of the intensity obtained from a ESE Quanti reader. There was a direct correlation between the analyte (MTB 38 kDa monoclonal antibody) concentration and the intensity of the test line. The intensity increased with an increase in the concentration of MTB 38 kDa monoclonal antibody, while in contrast, an increase in analyte concentration decreased the intensity of the control line. © 2013 Published by Elsevier B.V.

The DA antagonist tiapride impairs context-related extinction learning in a novel context without affecting renewal

PubMed Central

Lissek, Silke; Glaubitz, Benjamin; Wolf, Oliver T.; Tegenthoff, Martin

2015-01-01

Renewal describes the recovery of an extinguished response if recall is tested in a context different from the extinction context. Behavioral studies demonstrated that attention to relevant context strengthens renewal. Neurotransmitters mediating attention and learning such as the dopaminergic (DA) system presumably modulate extinction learning and renewal. However, the role of DA for non-fear-based extinction learning and renewal in humans has not yet been investigated. This fMRI study investigated effects of DA-antagonism upon context-related extinction in a predictive learning task in which extinction occurred either in a novel (ABA) or an unchanged (AAA) context. The tiapride-treated group (TIA) showed significantly impaired ABA extinction learning and a significant within-group difference between ABA and AAA extinction, compared to placebo (PLAC). Groups did not differ in their level of ABA renewal. In ABA extinction, TIA showed reduced activation in dlPFC and OFC, hippocampus, and temporal regions. Across groups, activation in PFC and hippocampus correlated negatively with ABA extinction errors. Results suggest that in context-related extinction learning DA in PFC and hippocampus is involved in readjusting the cue-outcome relationship in the presence of a novel context. However, relating context to the appropriate association during recall does not appear to rely exclusively on DA signaling. PMID:26388752

Wirelessly controlled micro- and nanostructures for bioapplications

NASA Astrophysics Data System (ADS)

Lindo, Andre Machado

Apresentar uma contribuicao para a caracterizacao e compreensao do comportamento hidrodinâmico da laguna Ria de Aveiro, baseada num estudo experimental e num estudo de modelacao numerica, e o objectivo deste trabalho. As caracteristicas hidrologicas da Ria de Aveiro foram investigadas atraves da realizacao de varias campanhas de amostragem, tendo sido efectuadas medicoes de altura de agua, salinidade, temperatura da agua e velocidade da corrente em varias estacoes distribuidas ao longo de quatro canais principais da laguna. None

Ultrasonic irradiation enhanced the ability of Fluorescein-DA-Fe(III) on sonodynamic and sonocatalytic damages of DNA molecules.

PubMed

Wu, Qiong; Chen, Xia; Jia, Lizhen; Wang, Yi; Sun, Ying; Huang, Xingjun; Shen, Yuxiang; Wang, Jun

2017-11-01

The interaction of DNA with Bis [N,N-bis (carboxymethyl) aminomethyl] fluorescein-Ferrous(III) (Fluorescein-DA-Fe(III)) with dual functional (sonodynamic and sonocatalytic) activity was studied by UV-vis spectroscopy, fluorescence spectroscopy, FT-IR spectroscopy, circular dichroism (CD) spectroscopy and viscosity measurements. And then, the damage of DNA caused by Fluorescein-DA-Fe(III) under ultrasonic irradiation (US) was researched by agarose gel electrophoresis and cytotoxicity assay. Meanwhile, some influenced factors such as ultrasonic irradiation time and Fluorescein-DA-Fe(III) concentration on the damage degree of DNA molecules were also examined. As a control, for Bis [N,N-bis (carboxymethyl) aminomethyl] fluorescein (Fluorescein-DA), the same experiments were carried out. The results showed that both Fluorescein-DA-Fe(III) and Fluorescein-DA can interact with DNA molecules. Under ultrasonic irradiation, Fluorescein-DA shows sonodynamic activity, which can damage DNA molecules. While, in the presence of Fe(III) ion, the Fluorescein-DA-Fe(III) displays not only sonodynamic activity but also sonocatalytic activity under ultrasonic irradiation, which injures DNA more serious than Fluorescein-DA. The researches confirmed the dual function (sonodynamic activity and sonocatalytic activity) of Fluorescein-DA-Fe(III) and expanded the usage of Fluorescein-DA-Fe(III) as a sonosensitizer in sonodynamic therapy (SDT). Copyright © 2017 Elsevier B.V. All rights reserved.

Domoic acid toxicokinetics in Dungeness crabs: new insights into mechanisms that regulate bioaccumulation.

PubMed

Schultz, Irvin R; Skillman, Ann; Sloan-Evans, Siobhan; Woodruff, Dana

2013-09-15

Domoic acid (DA) is an excitatory neurotoxic amino acid produced by several marine algal species and is the causative agent of amnesic shellfish poisoning. Profound differences in the toxicokinetics of DA have been identified in a wide variety of shellfish. We characterized the toxicokinetics of DA in Dungeness crabs (Metacarcinus magister) after oral and intravascular dosing (IV) using a variety of doses ranging from 0.1 to 20mg/kg. After a 1mg/kg oral dose, DA disappeared from the foregut within 2h and largely accumulated in the hepatopancreas, with hemolymph and other tissues having 100-1000 times lower concentrations. After IV dosing, hemolymph concentrations of DA were unexpectedly high and toxicokinetic analysis indicated the steady-state volume of distribution (Vss) was 123-197 ml/kg, which is well below the hemolymph volume of 350 ml/kg for crabs. This indicated only limited extravascular distribution of DA was occurring after IV injection, which is surprising considering the capacity of the hepatopancreas to sequester DA after oral dosing. Additional studies measured the partitioning of DA in hepatopancreas cellular and subcellular fractions. The subcellular distribution of DA was primarily associated with the S8 fraction and could be filtered through a 30,000 MW cut-off filter, indicating DA was not appreciably bound to macromolecules. Interestingly, very little (<0.4%) of the total hepatopancreas DA tissue content was associated with the cellular fraction isolated after dissociation and separation from tissue fragments. The in vivo and in vitro results led us to hypothesize that DA uptake and distribution is regulated by crustacean orthologs of ATP-binding cassette (ABC) type transporters. We tested this hypothesis by co-exposing crabs to DA and known inhibitors of ABC transporters (verapamil, cyclosporine A and MK-571) and through in vitro studies using isolated hepatopancreas tissue and mixed cell suspensions prepared from hepatopancreas tissue. The in vivo results were inconclusive in that the toxicokinetics of DA was not consistently altered by co-administration of the inhibitors. Two exceptions were MK-571, which significantly increased the total body clearance of DA and co-administration of verapamil, which significantly increased the hepatopancreas tissue content of DA 24h after IV injection. Isolated pieces of hepatopancreas tissue were able to readily absorb DA from incubation media, but mixed cell suspensions did not. The absorption of DA or lack thereof was largely unaffected by co-incubation with verapamil although cell suspensions appeared to accumulate small quantities of DA in the presence of verapamil. Collectively, the results of this study suggest DA accumulates in the extracellular spaces of the hepatopancreas, such as the tubular lumen. Under natural circumstances, crabs feeding on contaminated shellfish would be expected to readily absorb DA, which is then stored and slowly eliminated in urine. If the DA exposure level exceeds the storage capacity of the tissue (as occurred with the 20mg/kg dose), breakthrough occurs resulting in much higher systemic exposure and potential for DA toxicity. Copyright © 2013 Elsevier B.V. All rights reserved.

Pathomechanisms of Dopamine Dysregulation in DYT1 Dystonia: Targets for Therapeutics

DTIC Science & Technology

2016-10-01

DA release in DYT1(ΔE) knockin mice by assessing VMAT2 function, vesicle utilization, the ultrastructure of DA terminals, and D2 DA...in slice, the ultrastructure of DA terminals, D2 DA autoreceptor function nicotinic AChR (nAChR) heteroreceptors function. 2) To determine the

Phosphorylation of Tat-interactive protein 60 kDa by protein kinase C epsilon is important for its subcellular localisation.

PubMed

Sapountzi, Vasileia; Logan, Ian R; Nelson, Glyn; Cook, Susan; Robson, Craig N

2008-01-01

Tat-interactive protein 60 kDa is a nuclear acetyltransferase that both coactivates and corepresses transcription factors and has a definitive function in the DNA damage response. Here, we provide evidence that Tat-interactive protein 60 kDa is phosphorylated by protein kinase C epsilon. In vitro, protein kinase C epsilon phosphorylates Tat-interactive protein 60 kDa on at least two sites within the acetyltransferase domain. In whole cells, activation of protein kinase C increases the levels of phosphorylated Tat-interactive protein 60 kDa and the interaction of Tat-interactive protein 60 kDa with protein kinase C epsilon. A phosphomimetic mutant Tat-interactive protein 60 kDa has distinct subcellular localisation compared to the wild-type protein in whole cells. Taken together, these findings suggest that the protein kinase C epsilon phosphorylation sites on Tat-interactive protein 60 kDa are important for its subcellular localisation. Regulation of the subcellular localisation of Tat-interactive protein 60 kDa via phosphorylation provides a novel means of controlling Tat-interactive protein 60 kDa function.

Cocaine inhibition of nicotinic acetylcholine receptors influences dopamine release

PubMed Central

Acevedo-Rodriguez, Alexandra; Zhang, Lifen; Zhou, Fuwen; Gong, Suzhen; Gu, Howard; De Biasi, Mariella; Zhou, Fu-Ming; Dani, John A.

2014-01-01

Nicotinic acetylcholine receptors (nAChRs) potently regulate dopamine (DA) release in the striatum and alter cocaine's ability to reinforce behaviors. Since cocaine is a weak nAChR inhibitor, we hypothesized that cocaine may alter DA release by inhibiting the nAChRs in DA terminals in the striatum and thus contribute to cocaine's reinforcing properties primarily associated with the inhibition of DA transporters. We found that biologically relevant concentrations of cocaine can mildly inhibit nAChR-mediated currents in midbrain DA neurons and consequently alter DA release in the dorsal and ventral striatum. At very high concentrations, cocaine also inhibits voltage-gated Na channels in DA neurons. Furthermore, our results show that partial inhibition of nAChRs by cocaine reduces evoked DA release. This diminution of DA release via nAChR inhibition more strongly influences release evoked at low or tonic stimulation frequencies than at higher (phasic) stimulation frequencies, particularly in the dorsolateral striatum. This cocaine-induced shift favoring phasic DA release may contribute to the enhanced saliency and motivational value of cocaine-associated memories and behaviors. PMID:25237305

Global and disease-associated genetic variation in the human Fanconi anemia gene family.

PubMed

Rogers, Kai J; Fu, Wenqing; Akey, Joshua M; Monnat, Raymond J

2014-12-20

Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population genetic variation in FANC genes and the segregation of this variation in the human population, we identified 2948 unique FANC gene variants including 493 FA DA variants across 57,240 potential base pair variation sites in the 16 FANC genes. We then analyzed the segregation of this variation in the 7578 subjects included in the Exome Sequencing Project (ESP) and the 1000 Genomes Project (1KGP). There was a remarkably high frequency of FA DA variants in ESP/1KGP subjects: at least 1 FA DA variant was identified in 78.5% (5950 of 7578) individuals included in these two studies. Six widely used functional prediction algorithms correctly identified only a third of the known, DA FANC missense variants. We also identified FA DA variants that may be good candidates for different types of mutation-specific therapies. Our results demonstrate the power of direct DNA sequencing to detect, estimate the frequency of and follow the segregation of deleterious genetic variation in human populations. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Determination of Domoic Acid in Plankton Net Samples from Golden Horn Estuary, Turkey, Using HPLC with Fluorescence Detection.

PubMed

Dursun, Fuat; Ünlü, Selma; Yurdun, Türkan

2018-03-01

This study focused on the fluctuations of domoic acid (DA) levels in plankton net samples collected from the Golden Horn Estuary (GHE), Turkey, between August 2011 and July 2012. DA concentrations were determined by high-performance liquid chromatography (HPLC), using a fluorenylmethoxycarbonyl (FMOC) derivatization technique. Monthly and biweekly data were evaluated with environmental variables, and their influence on DA production is discussed. DA levels in plankton net samples varied between 0.36 and 94.34 µg L - 1 . DA levels showed remarkable seasonal variation and they were generally higher in May, 2012, but no DA was detected between February and April, 2012. DA production was mostly controlled by temperature, with nitrate and silicate limitations being secondary factors that influenced DA concentrations.

Packaging of the virion host shutoff (Vhs) protein of herpes simplex virus: two forms of the Vhs polypeptide are associated with intranuclear B and C capsids, but only one is associated with enveloped virions.

PubMed

Read, G Sullivan; Patterson, Mary

2007-02-01

The virion host shutoff (Vhs) protein (UL41) is a minor component of herpes simplex virus virions which, following penetration, accelerates turnover of host and viral mRNAs. Infected cells contain 58-kDa and 59.5-kDa forms of Vhs, which differ in the extent of phosphorylation, yet only a 58-kDa polypeptide is incorporated into virions. In pulse-chase experiments, the primary Vhs translation product comigrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with the 58-kDa virion polypeptide, and could be chased to 59.5 kDa. While both 59.5-kDa and 58-kDa forms were found in nuclear and cytoplasmic fractions, the 59.5-kDa form was significantly enriched in the nucleus. Both forms were associated with intranuclear B and C capsids, yet only the 58-kDa polypeptide was found in enveloped cytoplasmic virions. A 58-kDa form, but not the 59.5-kDa form, was found in L particles, noninfectious particles that contain an envelope and tegument but no capsid. The data suggest that virions contain two populations of Vhs that are packaged by different pathways. In the first pathway, the primary translation product is processed to 59.5 kDa, is transported to the nucleus, binds intranuclear capsids, and is converted to 58 kDa at some stage prior to final envelopment. The second pathway does not involve the 59.5-kDa form or interactions between Vhs and capsids. Instead, the primary translation product is phosphorylated to the 58-kDa virion form and packaged through interactions with other tegument proteins in the cytoplasm or viral envelope proteins at the site of final envelopment.

Within-family environmental transmission of drug abuse: a Swedish national study.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Sundquist, Kristina; Sundquist, Jan

2013-02-01

CONTEXT Drug abuse (DA) strongly runs in families. Does this result solely from genetic factors or does the family environment contribute? OBJECTIVE To determine the familial environmental contribution to the risk for DA. DESIGN Follow-up in 9 public databases (1961-2009) in siblings and spouses. SETTING Sweden. PARTICIPANTS A total of 137 199 sibling pairs and 7561 spousal pairs containing a proband with DA and matched control probands. MAIN OUTCOME MEASURES Drug abuse recorded in medical, legal, or pharmacy registry records. RESULTS In the best-fit model, which contained significant linear, quadratic, and cubic effects, among full sibling pairs containing a proband with DA, the relative risk for DA in the sibling declined from more than 6.0 for siblings born within 2 years of each other to less than 4.5 when born 10 years apart. Controlling for age differences in full sibling pairs, the hazard rate for DA in a sibling when the affected proband was older vs younger was 1.42 (95% CI, 1.31-1.54). In the best-fit model, which contained significant linear, quadratic, and cubic effects, among spousal pairs containing a proband with DA, the relative risk for DA in the spouse declined from more than 25.0 within 1 year of proband DA registration to 6.0 after 5 years. CONCLUSIONS Controlling for genetic effects by examining only full siblings, sibling resemblance for the risk for DA was significantly greater in pairs closer vs more distant in age. Older siblings more strongly transmitted the risk for DA to their younger siblings than vice versa. After one spouse is registered for DA, the other spouse has a large short-lived increase in DA risk. These results support strong familial environmental influences on DA at various life stages. A complete understanding of the familial transmission of DA will require knowledge of how genetic and familial environmental risk factors act and interact over development.

DA-9801 promotes neurite outgrowth via ERK1/2-CREB pathway in PC12 cells.

PubMed

Won, Jong Hoon; Ahn, Kyong Hoon; Back, Moon Jung; Ha, Hae Chan; Jang, Ji Min; Kim, Ha Hyung; Choi, Sang-Zin; Son, Miwon; Kim, Dae Kyong

2015-01-01

In the present study, we examined the mechanisms underlying the effect of DA-9801 on neurite outgrowth. We found that DA-9801 elicits its effects via the mitogen-activated protein kinase (MEK) extracellular signal-regulated kinase (ERK)1/2-cAMP response element-binding protein (CREB) pathway. DA-9801, an extract from a mixture of Dioscorea japonica and Dioscorea nipponica, was reported to promote neurite outgrowth in PC12 cells. The effects of DA-9801 on cell viability and expression of neuronal markers were evaluated in PC12 cells. To investigate DA-9801 action, specific inhibitors targeting the ERK signaling cascade were used. No cytotoxicity was observed in PC12 cells at DA-9801 concentrations of less than 30 µg/mL. In the presence of nerve growth factor (NGF, 2 ng/mL), DA-9801 promoted neurite outgrowth and increased the relative mRNA levels of neurofilament-L (NF-L), a marker of neuronal differentiation. The Raf-1 inhibitor GW5074 and MEK inhibitor PD98059 significantly attenuated DA-9801-induced neurite outgrowth. Additionally, the MEK1 and MEK2 inhibitor SL327 significantly attenuated the increase in the percentage of neurite-bearing PC12 cells induced by DA-9801 treatment. Conversely, the selective p38 mitogen-activated protein kinase inhibitor SB203580 did not attenuate the DA-9801 treatment-induced increase in the percentage of neurite-bearing PC12 cells. DA-9801 enhanced the phosphorylation of ERK1/2 and CREB in PC12 cells incubated with and without NGF. Pretreatment with PD98059 blocked the DA-9801-induced phosphorylation of ERK1/2 and CREB. In conclusion, DA-9801 induces neurite outgrowth by affecting the ERK1/2-CREB signaling pathway. Insights into the mechanism underlying this effect of DA-9801 may suggest novel potential strategies for the treatment of peripheral neuropathy.

Toward development of an in vitro model of methamphetamine-induced dopamine nerve terminal toxicity.

PubMed

Kim, S; Westphalen, R; Callahan, B; Hatzidimitriou, G; Yuan, J; Ricaurte, G A

2000-05-01

To develop an in vitro model of methamphetamine (METH)-induced dopamine (DA) neurotoxicity, striatal synaptosomes were incubated at 37 degrees C with METH for different periods of time (10-80 min), washed once, then tested for DA transporter function at 37 degrees C. METH produced time- and dose-dependent reductions in the V(max) of DA uptake, without producing any change in K(m). Incubation of synaptosomes with the DA neurotoxins 1-methyl-4-phenyl-pyridinium ion, 6-hydroxydopamine, and amphetamine under similar conditions produced comparable effects. In contrast, incubation with fenfluramine, a serotonin neurotoxin, did not. METH-induced decreases in DA uptake were selective, insofar as striatal glutamate uptake was unaffected. Various DA transporter blockers (cocaine, methylphenidate, and bupropion) afforded complete protection against METH-induced decreases in DA uptake, without producing any effect themselves. METH's effects were also temperature dependent, with greater decreases in DA uptake occurring at higher temperatures. Tests for residual drug revealed small amounts (0.1-0.2 microM) of remaining METH, but kinetic studies indicated that decreases in DA uptake were not likely to be due to METH acting as a competitive inhibitor of DA uptake. Decreases in the V(max) of DA uptake were not accompanied by decreases in B(max) of [(3)H]WIN 35,428 binding, possibly because there is no mechanism for removing damaged DA nerve endings from the in vitro preparation Collectively, these results give good support to the development of a valid in vitro model that may prove helpful for elucidating the mechanisms underlying METH-induced DA neurotoxicity.

Dynamic Assessment of Language Disabilities

ERIC Educational Resources Information Center

Martin, Deirdre

2015-01-01

The paper reports a study of a narrative-based Dynamic Assessment (DA) procedure developed in the USA that is used in the UK with children with developmental language disabilities. Three monolingual English children with language disabilities are assessed by a speech/language pathologist/therapist who is learning to work with DA in collaboration…

Women and Technical Professions. Leonardo da Vinci Series: Good Practices.

ERIC Educational Resources Information Center

Commission of the European Communities, Brussels (Belgium). Directorate-General for Education and Culture.

This document profiles programs for women in technical professions that are offered through the European Commission's Leonardo da Vinci program. The following programs are profiled: (1) Artemis and Diana (vocational guidance programs to help direct girls toward technology-related careers); (2) CEEWIT (an Internet-based information and…

The Cosmic Dust Analyzer for Cassini

NASA Technical Reports Server (NTRS)

Bradley, James G.; Gruen, Eberhard; Srama, Ralf

1996-01-01

The Cosmic Dust Analyzer (CDA) is designed to characterize the dust environment in interplanetary space, in the Jovian and in the Saturnian systems. The instrument consists of two major components, the Dust Analyzer (DA) and the High Rate Detector (HRD). The DA has a large aperture to provide a large cross section for detection in low flux environments. The DA has the capability of determining dust particle mass, velocity, flight direction, charge, and chemical composition. The chemical composition is determined by the Chemical Analyzer system based on a time-of-flight mass spectrometer. The DA is capable of making full measurements up to one impact/second. The HRD contains two smaller PVDF detectors and electronics designed to characterize dust particle masses at impact rates up to 10(exp 4) impacts/second. These high impact rates are expected during Saturn ring, plane crossings.

Health and innovation: economic dynamics and Welfare State in Brazil.

PubMed

Gadelha, Carlos Augusto Grabois; Braga, Patrícia Seixas da Costa

2016-11-03

The effective enforcement of the access to healthcare as fundamental right requires an important theoretical and political effort at linking the often contradictory economic and social dimensions of development. This study suggests the need for a systemic view of policies related to the industrial base and innovation in health and the construction of the Brazilian Unified National Health System (SUS). The authors investigate the relations between health, innovation, and development, seeking to show and update the political, economic, and social determinants of the recent Brazilian experience with the Health Economic-Industrial Complex (HEIC). They discuss how the agenda for innovation and domestic industrial production in health gained a central place in the project for construction of the SUS. The article thus seeks to link inherent issues from the agenda for development, production, and innovation to social policy in healthcare, as observed in recent years, and based on this analysis, points to political and conceptual challenges for implementing the SUS, especially as regards strengthening its technological and industrial base. As a byproduct, the article develops an analytical and factual focus on the consolidation of the HEIC in Brazil, both as a dynamic vector of industrial development, generating investment, income, employment, and innovations, and as a decisive element for reducing vulnerability and structural dependence in health. The authors aim to show that strengthening the SUS and orienting it to social needs is an essential part of building a social Welfare State in Brazil. Resumo: A efetivação da saúde como um direito fundamental exige importante esforço, teórico e político, de articulação das dimensões econômicas e sociais, por vezes contraditórias, do desenvolvimento. Este trabalho indica a necessidade de um olhar sistêmico das políticas relacionadas à base produtiva e de inovação em saúde e à construção do Sistema Único de Saúde (SUS). Investiga as relações entre saúde, inovação e desenvolvimento, buscando mostrar e atualizar os determinantes políticos, econômicos e sociais da experiência brasileira recente relacionada ao Complexo Econômico-Industrial da Saúde (CEIS). Mostra como a agenda da inovação e da produção nacional em saúde ganhou centralidade no projeto de construção do SUS. O artigo procura, assim, articular questões inerentes à agenda do desenvolvimento, da produção e da inovação com a política social em saúde, tal como observado nos últimos anos e, valendo-se de sua análise, aponta desafios políticos e conceituais para a efetivação do SUS, em especial no que se refere ao fortalecimento de sua base tecnológica e produtiva. Como desdobramento, desenvolve um enfoque analítico e factual que relaciona a consolidação do CEIS no Brasil tanto como um vetor dinâmico do desenvolvimento industrial, gerando investimento, renda, emprego e inovações, quanto como elemento decisivo para a redução da vulnerabilidade e da dependência estrutural em saúde. Procura mostrar que seu fortalecimento e direcionamento para as necessidades sociais é parte essencial da construção de um Estado de Bem-Estar Social no Brasi.

Metabolic regulation of lateral hypothalamic glucose-inhibited orexin neurons may influence midbrain reward neurocircuitry.

PubMed

Sheng, Zhenyu; Santiago, Ammy M; Thomas, Mark P; Routh, Vanessa H

2014-09-01

Lateral hypothalamic area (LHA) orexin neurons modulate reward-based feeding by activating ventral tegmental area (VTA) dopamine (DA) neurons. We hypothesize that signals of peripheral energy status influence reward-based feeding by modulating the glucose sensitivity of LHA orexin glucose-inhibited (GI) neurons. This hypothesis was tested using electrophysiological recordings of LHA orexin-GI neurons in brain slices from 4 to 6week old male mice whose orexin neurons express green fluorescent protein (GFP) or putative VTA-DA neurons from C57Bl/6 mice. Low glucose directly activated ~60% of LHA orexin-GFP neurons in both whole cell and cell attached recordings. Leptin indirectly reduced and ghrelin directly enhanced the activation of LHA orexin-GI neurons by glucose decreases from 2.5 to 0.1mM by 53±12% (n=16, P<0.001) and 41±24% (n=8, P<0.05), respectively. GABA or neurotensin receptor blockade prevented leptin's effect on glucose sensitivity. Fasting increased activation of LHA orexin-GI neurons by decreased glucose, as would be predicted by these hormonal effects. We also evaluated putative VTA-DA neurons in a novel horizontal slice preparation containing the LHA and VTA. Decreased glucose increased the frequency of spontaneous excitatory post-synaptic currents (sEPSCs; 125 ± 40%, n=9, P<0.05) and action potentials (n=9; P<0.05) in 45% (9/20) of VTA DA neurons. sEPSCs were completely blocked by AMPA and NMDA glutamate receptor antagonists (CNQX 20 μM, n=4; APV 20μM, n=4; respectively), demonstrating that these sEPSCs were mediated by glutamatergic transmission onto VTA DA neurons. Orexin-1 but not 2 receptor antagonism with SB334867 (10μM; n=9) and TCS-OX2-29 (2μM; n=5), respectively, blocks the effects of decreased glucose on VTA DA neurons. Thus, decreased glucose increases orexin-dependent excitatory glutamate neurotransmission onto VTA DA neurons. These data suggest that the glucose sensitivity of LHA orexin-GI neurons links metabolic state and reward-based feeding. Copyright © 2014 Elsevier Inc. All rights reserved.

Integrative literature review of the reported uses of serological tests in leprosy management.

PubMed

Fabri, Angélica da Conceição Oliveira Coelho; Carvalho, Ana Paula Mendes; Vieira, Nayara Figueiredo; Bueno, Isabela de Caux; Rodrigues, Rayssa Nogueira; Monteiro, Thayenne Barrozo Mota; Correa-Oliveira, Rodrigo; Duthie, Malcolm S; Lana, Francisco Carlos Félix

2016-04-01

An integrative literature review was conducted to synthesize available publications regarding the potential use of serological tests in leprosy programs. We searched the databases Literatura Latino-Americana e do Caribe em Ciências da Saúde, Índice Bibliográfico Espanhol em Ciências da Saúde, Acervo da Biblioteca da Organização Pan-Americana da Saúde, Medical Literature Analysis and Retrieval System Online, Hanseníase, National Library of Medicine, Scopus, Ovid, Cinahl, and Web of Science for articles investigating the use of serological tests for antibodies against phenolic glycolipid-I (PGL-I), ML0405, ML2331, leprosy IDRI diagnostic-1 (LID-1), and natural disaccharide octyl-leprosy IDRI diagnostic-1 (NDO-LID). From an initial pool of 3.514 articles, 40 full-length articles fulfilled our inclusion criteria. Based on these papers, we concluded that these antibodies can be used to assist in diagnosing leprosy, detecting neuritis, monitoring therapeutic efficacy, and monitoring household contacts or at-risk populations in leprosy-endemic areas. Thus, available data suggest that serological tests could contribute substantially to leprosy management.

Graphene-loaded nanofiber-modified electrodes for the ultrasensitive determination of dopamine.

PubMed

Rodthongkum, Nadnudda; Ruecha, Nipapan; Rangkupan, Ratthapol; Vachet, Richard W; Chailapakul, Orawon

2013-12-04

A novel and highly sensitive electrochemical system based on electrospun graphene/polyaniline/polystyrene (G/PANI/PS) nanofiber-modified screen-printed carbon electrodes has been developed for dopamine (DA) determination. A dramatic increase (9 times) in the current signal for the redox reaction of a standard, ferri/ferrocyanide [Fe(CN)6](3-/4-) couple was found when compared to an unmodified electrode. This modified electrode also exhibited favorable electron transfer kinetics and excellent electrocatalytic activity toward the oxidation of DA. When used together with square wave voltammetry (SWV), DA can be selectively determined in the presence of the common interferents (i.e. ascorbic acid and uric acid). Under optimal conditions, a very low limit of detection (0.05 nM) and limit of quantification (0.30 nM) were achieved for DA. In addition, a wide dynamic range of 0.1 nM to 100 μM was found for this electrode system. Finally, the system can be successfully applied to determine DA in complex biological environment (e.g. human serum, urine) with excellent reproducibility. Copyright © 2013 Elsevier B.V. All rights reserved.

Organic transistor memory with a charge storage molecular double-floating-gate monolayer.

PubMed

Tseng, Chiao-Wei; Huang, Ding-Chi; Tao, Yu-Tai

2015-05-13

A flexible, low-voltage, and nonvolatile memory device was fabricated by implanting a functional monolayer on an aluminum oxide dielectric surface in a pentacene-based organic transistor. The monolayer-forming molecule contains a phosphonic acid group as the anchoring moiety and a charge-trapping core group flanked between two alkyl chain spacers as the charge trapping site. The memory characteristics strongly depend on the monolayer used due to the localized charge-trapping capability for different core groups, including the diacetylenic (DA) unit as the hole carrier trap, the naphthalenetetracarboxyldiimide (ND) unit as the electron carrier trap, and the one with both DA and ND units present, respectively. The device with the monolayer carrying both DA and ND groups has a larger memory window than that for the one containing DA only and a longer retention time than that for the one containing DA or ND only, giving a memory window of 1.4 V and a retention time around 10(9) s. This device with hybrid organic monolayer/inorganic dielectrics also exhibited rather stable device characteristics upon bending of the polymeric substrate.

Direct electrochemistry of dopamine on gold-Agaricus bisporus laccase enzyme electrode: characterization and quantitative detection.

PubMed

Shervedani, Reza Karimi; Amini, Akbar

2012-04-01

Direct electrochemistry of a new laccase enzyme immobilized on gold and its application as a biosensor for dopamine (DA) are investigated by voltammetry and electrochemical impedance spectroscopy. The sensor demonstrated a redox adsorption behavior with E(0') = + 180 mV vs. Ag/AgCl for immobilized Agaricus bisporus laccase (LacAB) enzyme. The MPA platform was assembled on Au with and without utilization of ultrasounds. Excellent results were obtained by using the enzyme electrode fabricated based on MPA assembled with sonication. The LacAB immobilized in this condition showed a large electrocatalytic activity for oxidation of DA. Accordingly, a third-generation (mediator free) biosensor was constructed for DA. The DA concentration could be measured in the linear range of 0.5 to 13.0 and 47.0 to 430.0 μmol L(-1) with correlation coefficients of 0.999 and 0.989, respectively, and a detection limit of 29.0 nmol L(-1). The biosensor was successfully tested for determination of DA in human blood plasma and pharmaceutical samples. Copyright © 2011 Elsevier B.V. All rights reserved.

[Applicability of the da Vinci robotic system in the skull base surgical approach. Preclinical investigation].

PubMed

Fernandez-Nogueras Jimenez, Francisco J; Segura Fernandez-Nogueras, Miguel; Jouma Katati, Majed; Arraez Sanchez, Miguel Ángel; Roda Murillo, Olga; Sánchez Montesinos, Indalecio

2015-01-01

The role of robotic surgery is well established in various specialties such as urology and general surgery, but not in others such as neurosurgery and otolaryngology. In the case of surgery of the skull base, it has just emerged from an experimental phase. To investigate possible applications of the da Vinci surgical robot in transoral skull base surgery, comparing it with the authors' experience using conventional endoscopic transnasal surgery in the same region. A transoral transpalatal approach to the nasopharynx and medial skull base was performed on 4 cryopreserved cadaver heads. We used the da Vinci robot, a 30° standard endoscope 12mm thick, dual camera and dual illumination, Maryland forceps on the left terminal and curved scissors on the right, both 8mm thick. Bone drilling was performed manually. For the anatomical study of this region, we used 0.5cm axial slices from a plastinated cadaver head. Various skull base structures at different depths were reached with relative ease with the robot terminals Transoral robotic surgery with the da Vinci system provides potential advantages over conventional endoscopic transnasal surgery in the surgical approach to this region. Copyright © 2014 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Evaluation of the trade-offs encountered in planning and treating locally advanced head and neck cancer: intensity-modulated radiation therapy vs dual-arc volumetric-modulated arc therapy

PubMed Central

Oliver, M; McConnell, D; Romani, M; McAllister, A; Pearce, A; Andronowski, A; Wang, X; Leszczynski, K

2012-01-01

Objective The primary purpose of this study was to assess the practical trade-offs between intensity-modulated radiation therapy (IMRT) and dual-arc volumetric-modulated arc therapy (DA-VMAT) for locally advanced head and neck cancer (HNC). Methods For 15 locally advanced HNC data sets, nine-field step-and-shoot IMRT plans and two full-rotation DA-VMAT treatment plans were created in the Pinnacle3 v. 9.0 (Philips Medical Systems, Fitchburg, WI) treatment planning environment and then delivered on a Clinac iX (Varian Medical Systems, Palo Alto, CA) to a cylindrical detector array. The treatment planning goals were organised into four groups based on their importance: (1) spinal cord, brainstem, optical structures; (2) planning target volumes; (3) parotids, mandible, larynx and brachial plexus; and (4) normal tissues. Results Compared with IMRT, DA-VMAT plans were of equal plan quality (p>0.05 for each group), able to be delivered in a shorter time (3.1 min vs 8.3 min, p<0.0001), delivered fewer monitor units (on average 28% fewer, p<0.0001) and produced similar delivery accuracy (p>0.05 at γ2%/2mm and γ3%/3mm). However, the VMAT plans took more planning time (28.9 min vs 7.7 min per cycle, p<0.0001) and required more data for a three-dimensional dose (20 times more, p<0.0001). Conclusions Nine-field step-and-shoot IMRT and DA-VMAT are both capable of meeting the majority of planning goals for locally advanced HNC. The main trade-offs between the techniques are shorter treatment time for DA-VMAT but longer planning time and the additional resources required for implementation of a new technology. Based on this study, our clinic has incorporated DA-VMAT for locally advanced HNC. Advances in knowledge DA-VMAT is a suitable alternative to IMRT for locally advanced HNC. PMID:22806619

Jeopardizing quality at the frontline of healthcare: prevalence and risk factors for disrespect and abuse during facility-based childbirth in Ethiopia

PubMed Central

Karim, Ali M; Ratcliffe, Hannah L; Betemariam, Wuleta; Langer, Ana

2018-01-01

Abstract Disrespect and abuse (D&A) experienced by women during facility-based childbirth has gained global recognition as a threat to eliminating preventable maternal mortality and morbidity. This study explored the frequency and associated factors of D&A in four rural health centres in Ethiopia. Experiences of women who delivered in these facilities were captured by direct observation of client-provider interaction (N = 193) and exit interview at time of discharge (N = 204). Incidence of D&A was observed in each facility, with failure to ask woman for preferred birth position most commonly observed [n = 162, 83.9%, 95% confidence interval (95% CI) 78.0–88.5%]. During exit interviews, 21.1% (n = 43, 95% CI 15.4–26.7%) of respondents reported at least one occurrence of D&A. Bivariate models using client characteristics and index birth experience showed that women’s reporting of D&A was significantly associated with childbirth complications [odds ratio (OR) = 7.98, 95% CI 3.70, 17.22], weekend delivery (OR = 0.17, 95% CI 0.05, 0.63) and no previous delivery at the facility (OR = 3.20, 95% CI 1.27, 8.05). Facility-level fixed-effect models found that experience of complications (OR = 15.51, 95% CI 4.38, 54.94) and weekend delivery (OR = 0.05, 95% CI 0.01–0.32) remained significantly and most strongly associated with self-reported D&A. These data suggest that addressing D&A in health centres in Ethiopia will require a sustained effort to improve infrastructure, support the health workforce in rural settings, enforce professional standards and target interventions to improve women’s experiences as part of quality of care initiatives. PMID:29309598

Vietnamese children and language-based processing tasks.

PubMed

Hwa-Froelich, Deborah A; Matsuo, Hisako

2005-07-01

Vietnamese children's performance on language-based processing tasks of fast-mapping (FM) word-learning and dynamic assessment (DA) word- and rule-learning tasks were investigated. Twenty-one first- and second-generation Vietnamese preschool children participated in this study. All children were enrolled in 2 Head Start programs in a large city in the Midwest. All children had passed a developmental assessment and routine speech, language, and hearing screenings. All participants were taught 4 invented monosyllabic words in an FM word task, an invented monosyllabic suffix rule (-po) meaning "a part of" in a DA rule task, and 4 invented bisyllabic words in a DA word task. Potential relationships among task performances were investigated. Receptive task performances, expressive task performances, and task totals were added to create receptive total, expressive total, and accumulated performance total (APT) scores. Relationships among receptive total, expressive total, and APT scores were also investigated. Significant correlations were found between FM word, DA rule, and the receptive total. The expressive total correlated with all task total scores, APT, age, and modifiability scores. Modifiability scores correlated with the two DA tasks, expressive total, and the APT. Findings indicate that FM word and the expressive total were positively correlated with most of the other tasks, composite totals, and age. Performance on language-based processing tasks may provide valuable information for separating typically developing Vietnamese preschool children from their peers with language disorders. Practitioners should consider linguistic characteristics of target stimuli. Comparisons should include task, receptive, expressive, and APT.

Cloning and sequencing of a gene encoding a 21-kilodalton outer membrane protein from Bordetella avium and expression of the gene in Salmonella typhimurium.

PubMed Central

Gentry-Weeks, C R; Hultsch, A L; Kelly, S M; Keith, J M; Curtiss, R

1992-01-01

Three gene libraries of Bordetella avium 197 DNA were prepared in Escherichia coli LE392 by using the cosmid vectors pCP13 and pYA2329, a derivative of pCP13 specifying spectinomycin resistance. The cosmid libraries were screened with convalescent-phase anti-B. avium turkey sera and polyclonal rabbit antisera against B. avium 197 outer membrane proteins. One E. coli recombinant clone produced a 56-kDa protein which reacted with convalescent-phase serum from a turkey infected with B. avium 197. In addition, five E. coli recombinant clones were identified which produced B. avium outer membrane proteins with molecular masses of 21, 38, 40, 43, and 48 kDa. At least one of these E. coli clones, which encoded the 21-kDa protein, reacted with both convalescent-phase turkey sera and antibody against B. avium 197 outer membrane proteins. The gene for the 21-kDa outer membrane protein was localized by Tn5seq1 mutagenesis, and the nucleotide sequence was determined by dideoxy sequencing. DNA sequence analysis of the 21-kDa protein revealed an open reading frame of 582 bases that resulted in a predicted protein of 194 amino acids. Comparison of the predicted amino acid sequence of the gene encoding the 21-kDa outer membrane protein with protein sequences in the National Biomedical Research Foundation protein sequence data base indicated significant homology to the OmpA proteins of Shigella dysenteriae, Enterobacter aerogenes, E. coli, and Salmonella typhimurium and to Neisseria gonorrhoeae outer membrane protein III, Haemophilus influenzae protein P6, and Pseudomonas aeruginosa porin protein F. The gene (ompA) encoding the B. avium 21-kDa protein hybridized with 4.1-kb DNA fragments from EcoRI-digested, chromosomal DNA of Bordetella pertussis and Bordetella bronchiseptica and with 6.0- and 3.2-kb DNA fragments from EcoRI-digested, chromosomal DNA of B. avium and B. avium-like DNA, respectively. A 6.75-kb DNA fragment encoding the B. avium 21-kDa protein was subcloned into the Asd+ vector pYA292, and the construct was introduced into the avirulent delta cya delta crp delta asd S. typhimurium chi 3987 for oral immunization of birds. The gene encoding the 21-kDa protein was expressed equivalently in B. avium 197, delta asd E. coli chi 6097, and S. typhimurium chi 3987 and was localized primarily in the cytoplasmic membrane and outer membrane. In preliminary studies on oral inoculation of turkey poults with S. typhimurium chi 3987 expressing the gene encoding the B. avium 21-kDa protein, it was determined that a single dose of the recombinant Salmonella vaccine failed to elicit serum antibodies against the 21-kDa protein and challenge with wild-type B. avium 197 resulted in colonization of the trachea and thymus with B. avium 197. Images PMID:1447140

The Effect of Dynamic Assessment on Adult Learners of Arabic: A Mixed-Method Study at the Defense Language Institute Foreign Language Center

ERIC Educational Resources Information Center

Fahmy, Mohsen M.

2013-01-01

Dynamic assessment (DA) is based on Vygotsky's (1978) sociocultural theory and his Zone of Proximal Development (ZPD). ZPD is the range of abilities bordered by the learner's assisted and independent performances. Previous studies showed promising results for DA in tutoring settings. However, they did not use proficiency-based rubrics to measure…

Prognosis of carotid dissecting aneurysms

PubMed Central

Larsson, Susanna C.; King, Alice; Madigan, Jeremy; Levi, Christopher; Norris, John W.

2017-01-01

Objective: To determine the natural history of dissecting aneurysm (DA) and whether DA is associated with an increased recurrent stroke risk and whether type of antithrombotic drugs (antiplatelets vs anticoagulants) modifies the persistence or development of DA. Methods: We included 264 patients with extracranial cervical artery dissection (CAD) from the Cervical Artery Dissection in Stroke Study (CADISS), a multicenter prospective study that compared antiplatelet with anticoagulation therapy. Logistic regression was used to estimate age- and sex-adjusted odds ratios. We conducted a systematic review of published studies assessing the natural history of DA and stroke risk in patients with non-surgically-treated extracranial CAD with DA. Results: In CADISS, DA was present in 24 of 264 patients at baseline. In 36 of 248 patients with follow-up neuroimaging at 3 months, 12 of the 24 baseline DAs persisted, and 24 new DA had developed. There was no association between treatment allocation (antiplatelets vs anticoagulants) and whether DA at baseline persisted at follow-up or whether new DA developed. During 12 months of follow-up, stroke occurred in 1 of 48 patients with DA and in 7 of 216 patients without DA (age- and sex-adjusted odds ratio 0.84; 95% confidence interval 0.10–7.31; p = 0.88). Published studies, mainly retrospective, showed a similarly low risk of stroke and no evidence of an increased stroke rate in patients with DA. Conclusions: The results of CADISS provide evidence suggesting that DAs may have benign prognosis and therefore medical treatment should be considered. PMID:28087823

A Behavioral and Genetic Dissection of Two Forms of Olfactory Plasticity in Caenorhabditis elegans: Adaptation and Habituation

PubMed Central

Bernhard, Nirit; van der Kooy, Derek

2000-01-01

Continuous presentation of an olfactory stimulus causes a decrement of the chemotaxis response in the nematode Caenorhabditis elegans. However, the differences between the learning process of habituation (a readily reversible decrease in behavioral response) and other types of olfactory plasticity such as adaptation (a decrement in response due to sensory fatigue, which cannot be dishabituated) have not been addressed. The volatile odorant diacetyl (DA) was used within a single paradigm to assess the distinct processes of olfactory adaptation and habituation. Preexposing and testing worms to 100% DA vapors caused a chemotaxis decrement that was not reversible despite the presentation of potentially dishabituating stimuli. This DA adaptation was abolished in worms with an odr-10 mutation (encoding a high-affinity DA receptor on the AWA neuron), even though naive chemotaxis remained unaffected. Conversely, DA adaptation remained intact in odr-1 mutants (defective in AWC neuron-mediated olfactory behavior), even though naive chemotaxis to DA decreased. Surprisingly, exposure to vapors of intermediate concentrations of DA (0.01% and 25%) did not cause worms to exhibit any response decrement. In contrast to preexposure to high DA concentrations, preexposure to low DA concentrations (0.001%) produced habituation of the chemotaxis response (a dishabituating stimulus could reverse the response decrement back to baseline levels). The distinct behavioral effects produced by DA preexposure highlight a concentration-dependent dissociation between two decremental olfactory processes: adaptation at high DA concentrations versus habituation at low DA concentrations. PMID:10940320

Bolevenine, a toxic protein from the Japanese toadstool Boletus venenatus.

PubMed

Matsuura, Masanori; Yamada, Mina; Saikawa, Yoko; Miyairi, Kazuo; Okuno, Toshikatsu; Konno, Katsuhiro; Uenishi, Jun'ichi; Hashimoto, Kimiko; Nakata, Masaya

2007-03-01

A toxic protein, called bolevenine, was isolated from the toxic mushroom Boletus venenatus based on its lethal effects on mice. On SDS-PAGE, in either the presence or absence of 2-mercaptoethanol, this protein showed a single band of approximately 12 kDa. In contrast, based on gel filtration and MALDI-TOFMS, its relative molecular mass was estimated to be approximately 30 kDa and approximately 33 kDa, respectively, indicating that the protein consists of three identical subunits. This toxin exhibited its lethal activity following injection at 10mg/kg into mice. The N-terminal amino acid sequence was determined up to 18, and found to be similar to the previously reported bolesatine, a toxic compound isolated from Boletus satanas.

Identification of an abundant 56 kDa protein implicated in food allergy as granule-bound starch synthase

USDA-ARS?s Scientific Manuscript database

Rice, the staple food of South and East Asian counties, is considered to be hypoallergenic. However, several clinical studies have documented rice-induced allergy in sensitive patients. Rice proteins with molecular weights of 14-16 kDa, 26 kDa, 33 kDa and 56 kDa have been identified as allergens. Re...

DaRT: A CALL System to Help Students Practice and Develop Reasoning Skills in Choosing English Articles.

ERIC Educational Resources Information Center

Yoshii, Rika; Milne, Alastair

1998-01-01

Describes DaRT, a computer assisted language-learning system for helping English-as-a-Second-Language students master English articles. DaRT uses a diagrammatic reasoning tool to present communicative contexts for exercises in choosing appropriate articles. This paper describes the development of DaRT and DaRT's system components and concludes…

No Significant Increase in the Δ4- and Δ7-Dafachronic Acid Concentration in the Long-Lived glp-1 Mutant, nor in the Mutants Defective in Dauer Formation.

PubMed

Li, Tie-Mei; Liu, Weilong; Lu, Shan; Zhang, Yan-Ping; Jia, Le-Mei; Chen, Jie; Li, Xiangke; Lei, Xiaoguang; Dong, Meng-Qiu

2015-05-12

The steroid hormone dafachronic acid (DA) regulates dauer formation and lifespan in Caenorhabditis elegans by binding to the nuclear receptor DAF-12. However, little is known about how DA concentrations change under various physiologic conditions and about how DA/DAF-12 signaling interacts with other signaling pathways that also regulate dauer formation and lifespan. Using a sensitive bioanalytical method, we quantified the endogenous DA concentrations in a long-lived germline-less glp-1 mutant and in the Dauer formation-defective (Daf-d) mutants daf-12, daf-16, daf-5, and daf-3. We found that the DA concentration in the glp-1 mutant was similar to that in the wild type (WT). This result is contrary to the long-held belief that germline loss-induced longevity involves increased DA production and suggests instead that this type of longevity involves an enhanced response to DA. We also found evidence suggesting that increased DA sensitivity underlies lifespan extension triggered by exogenous DA. At the L2/L3 stage, the DA concentration in a daf-12 null mutant decreased to 22% of the WT level. This finding is consistent with the previously proposed positive feedback regulation between DAF-12 and DA production. Surprisingly, the DA concentrations in the daf-16, daf-5, and daf-3 mutants were only 19-34% of the WT level at the L2/L3 stage, slightly greater than those in the Dauer formation-constitutive (Daf-c) mutants at the pre-dauer stage (4-15% of the WT L2 control). Our experimental evidence suggested that the positive feedback between DA and DAF-12 was partially induced in the three Daf-d mutants. Copyright © 2015 Li et al.

Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons.

PubMed

Diaz-Ruiz, Oscar; Zhang, Yajun; Shan, Lufei; Malik, Nasir; Hoffman, Alexander F; Ladenheim, Bruce; Cadet, Jean Lud; Lupica, Carl R; Tagliaferro, Adriana; Brusco, Alicia; Bäckman, Cristina M

2012-07-20

In the present study, we analyzed mice with a targeted deletion of β-catenin in DA neurons (DA-βcat KO mice) to address the functional significance of this molecule in the shaping of synaptic responses associated with motor learning and following exposure to drugs of abuse. Relative to controls, DA-βcat KO mice showed significant deficits in their ability to form long-term memories and displayed reduced expression of methamphetamine-induced behavioral sensitization after subsequent challenge doses with this drug, suggesting that motor learning and drug-induced learning plasticity are altered in these mice. Morphological analyses showed no changes in the number or distribution of tyrosine hydroxylase-labeled neurons in the ventral midbrain. While electrochemical measurements in the striatum determined no changes in acute DA release and uptake, a small but significant decrease in DA release was detected in mutant animals after prolonged repetitive stimulation, suggesting a possible deficit in the DA neurotransmitter vesicle reserve pool. However, electron microscopy analyses did not reveal significant differences in the content of synaptic vesicles per terminal, and striatal DA levels were unchanged in DA-βcat KO animals. In contrast, striatal mRNA levels for several markers known to regulate synaptic plasticity and DA neurotransmission were altered in DA-βcat KO mice. This study demonstrates that ablation of β-catenin in DA neurons leads to alterations of motor and reward-associated memories and to adaptations of the DA neurotransmitter system and suggests that β-catenin signaling in DA neurons is required to facilitate the synaptic remodeling underlying the consolidation of long-term memories.

RISING FROM THE ASHES: MID-INFRARED RE-BRIGHTENING OF THE IMPOSTOR SN 2010da IN NGC 300

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

Lau, Ryan M.; Ressler, Michael E.; Kasliwal, Mansi M.

2016-10-20

We present multi-epoch mid-infrared (IR) photometry and the optical discovery observations of the “impostor” supernova (SN) 2010da in NGC 300 using new and archival Spitzer Space Telescope images and ground-based observatories. The mid-infrared counterpart of SN 2010da was detected as Spitzer Infrared Intensive Transient Survey (SPIRITS) 14bme in the SPIRITS, an ongoing systematic search for IR transients. Before erupting on 2010 May 24, the SN 2010da progenitor exhibited a constant mid-IR flux at 3.6 and only a slight ∼10% decrease at 4.5 μ m between 2003 November and 2007 December. A sharp increase in the 3.6 μ m flux followedmore » by a rapid decrease measured ∼150 days before and ∼80 days after the initial outburst, respectively, reveal a mid-IR counterpart to the coincident optical and high luminosity X-ray outbursts. At late times, after the outburst (∼2000 days), the 3.6 and 4.5 μ m emission increased to over a factor of two times the progenitor flux and is currently observed (as of 2016 Feb) to be fading, but still above the progenitor flux. We attribute the re-brightening mid-IR emission to continued dust production and increasing luminosity of the surviving system associated with SN 2010da. We analyze the evolution of the dust temperature ( T {sub d} ∼ 700–1000 K), mass ( M {sub d} ∼ 0.5–3.8 × 10{sup −7} M {sub ⊙}), luminosity ( L {sub IR} ∼ 1.3–3.5 × 10{sup 4} L {sub ⊙}), and the equilibrium temperature radius ( R {sub eq} ∼ 6.4–12.2 au) in order to resolve the nature of SN 2010da. We address the leading interpretation of SN 2010da as an eruption from a luminous blue variable high-mass X-ray binary (HMXB) system. We propose that SN 2010da is instead a supergiant (sg)B[e]-HMXB based on similar luminosities and dust masses exhibited by two other known sgB[e]-HMXB systems. Additionally, the SN 2010da progenitor occupies a similar region on a mid-IR color–magnitude diagram (CMD) with known sgB[e] stars in the Large Magellanic Cloud. The lower limit estimated for the orbital eccentricity of the sgB[e]-HMXB ( e > 0.82) from X-ray luminosity measurements is high compared to known sgHMXBs and supports the claim that SN 2010da may be associated with a newly formed HMXB system.« less

Simultaneous Electrochemical Detection of Dopamine and Ascorbic Acid Using an Iron Oxide/Reduced Graphene Oxide Modified Glassy Carbon Electrode

PubMed Central

Peik-See, Teo; Pandikumar, Alagarsamy; Nay-Ming, Huang; Hong-Ngee, Lim; Sulaiman, Yusran

2014-01-01

The fabrication of an electrochemical sensor based on an iron oxide/graphene modified glassy carbon electrode (Fe3O4/rGO/GCE) and its simultaneous detection of dopamine (DA) and ascorbic acid (AA) is described here. The Fe3O4/rGO nanocomposite was synthesized via a simple, one step in-situ wet chemical method and characterized by different techniques. The presence of Fe3O4 nanoparticles on the surface of rGO sheets was confirmed by FESEM and TEM images. The electrochemical behavior of Fe3O4/rGO/GCE towards electrocatalytic oxidation of DA was investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) analysis. The electrochemical studies revealed that the Fe3O4/rGO/GCE dramatically increased the current response against the DA, due to the synergistic effect emerged between Fe3O4 and rGO. This implies that Fe3O4/rGO/GCE could exhibit excellent electrocatalytic activity and remarkable electron transfer kinetics towards the oxidation of DA. Moreover, the modified sensor electrode portrayed sensitivity and selectivity for simultaneous determination of AA and DA. The observed DPVs response linearly depends on AA and DA concentration in the range of 1–9 mM and 0.5–100 μM, with correlation coefficients of 0.995 and 0.996, respectively. The detection limit of (S/N = 3) was found to be 0.42 and 0.12 μM for AA and DA, respectively. PMID:25195850

Simultaneous electrochemical detection of dopamine and ascorbic acid using an iron oxide/reduced graphene oxide modified glassy carbon electrode.

PubMed

Peik-See, Teo; Pandikumar, Alagarsamy; Nay-Ming, Huang; Hong-Ngee, Lim; Sulaiman, Yusran

2014-08-19

The fabrication of an electrochemical sensor based on an iron oxide/graphene modified glassy carbon electrode (Fe3O4/rGO/GCE) and its simultaneous detection of dopamine (DA) and ascorbic acid (AA) is described here. The Fe3O4/rGO nanocomposite was synthesized via a simple, one step in-situ wet chemical method and characterized by different techniques. The presence of Fe3O4 nanoparticles on the surface of rGO sheets was confirmed by FESEM and TEM images. The electrochemical behavior of Fe3O4/rGO/GCE towards electrocatalytic oxidation of DA was investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) analysis. The electrochemical studies revealed that the Fe3O4/rGO/GCE dramatically increased the current response against the DA, due to the synergistic effect emerged between Fe3O4 and rGO. This implies that Fe3O4/rGO/GCE could exhibit excellent electrocatalytic activity and remarkable electron transfer kinetics towards the oxidation of DA. Moreover, the modified sensor electrode portrayed sensitivity and selectivity for simultaneous determination of AA and DA. The observed DPVs response linearly depends on AA and DA concentration in the range of 1-9 mM and 0.5-100 µM, with correlation coefficients of 0.995 and 0.996, respectively. The detection limit of (S/N = 3) was found to be 0.42 and 0.12 µM for AA and DA, respectively.

Nonsynonymous substitution in abalone sperm fertilization genes exceeds substitution in introns and mitochondrial DNA

PubMed Central

Metz, Edward C.; Robles-Sikisaka, Refugio; Vacquier, Victor D.

1998-01-01

Strong positive Darwinian selection acts on two sperm fertilization proteins, lysin and 18-kDa protein, from abalone (Haliotis). To understand the phylogenetic context for this dramatic molecular evolution, we obtained sequences of mitochondrial cytochrome c oxidase subunit I (mtCOI), and genomic sequences of lysin, 18-kDa, and a G protein subunit. Based on mtDNA differentiation, four north Pacific abalone species diverged within the past 2 million years (Myr), and remaining north Pacific species diverged over a period of 4–20 Myr. Between-species nonsynonymous differences in lysin and 18-kDa exons exceed nucleotide differences in introns by 3.5- to 24-fold. Remarkably, in some comparisons nonsynonymous substitutions in lysin and 18-kDa genes exceed synonymous substitutions in mtCOI. Lysin and 18-kDa intron/exon segments were sequenced from multiple red abalone individuals collected over a 1,200-km range. Only two nucleotide changes and two sites of slippage variation were detected in a total of >29,000 nucleotides surveyed. However, polymorphism in mtCOI and a G protein intron was found in this species. This finding suggests that positive selection swept one lysin allele and one 18-kDa allele to fixation. Similarities between mtCOI and lysin gene trees indicate that rapid adaptive evolution of lysin has occurred consistently through the history of the group. Comparisons with mtCOI molecular clock calibrations suggest that nonsynonymous substitutions accumulate 2–50 times faster in lysin and 18-kDa genes than in rapidly evolving mammalian genes. PMID:9724763

A Subpopulation of Neurochemically-Identified Ventral Tegmental Area Dopamine Neurons Is Excited by Intravenous Cocaine

PubMed Central

Mejias-Aponte, Carlos A.; Ye, Changquan; Bonci, Antonello; Kiyatkin, Eugene A.

2015-01-01

Systemic administration of cocaine is thought to decrease the firing rates of ventral tegmental area (VTA) dopamine (DA) neurons. However, this view is based on categorizations of recorded neurons as DA neurons using preselected electrophysiological characteristics lacking neurochemical confirmation. Without applying cellular preselection, we recorded the impulse activity of VTA neurons in response to cocaine administration in anesthetized adult rats. The phenotype of recorded neurons was determined by their juxtacellular labeling and immunohistochemical detection of tyrosine hydroxylase (TH), a DA marker. We found that intravenous cocaine altered firing rates in the majority of recorded VTA neurons. Within the cocaine-responsive neurons, half of the population was excited and the other half was inhibited. Both populations had similar discharge rates and firing regularities, and most neurons did not exhibit changes in burst firing. Inhibited neurons were more abundant in the posterior VTA, whereas excited neurons were distributed evenly throughout the VTA. Cocaine-excited neurons were more likely to be excited by footshock. Within the subpopulation of TH-positive neurons, 36% were excited by cocaine and 64% were inhibited. Within the subpopulation of TH-negative neurons, 44% were excited and 28% were inhibited. Contrary to the prevailing view that all DA neurons are inhibited by cocaine, we found a subset of confirmed VTA DA neurons that is excited by systemic administration of cocaine. We provide evidence indicating that DA neurons are heterogeneous in their response to cocaine and that VTA non-DA neurons play an active role in processing systemic cocaine. PMID:25653355

The future of PanDA in ATLAS distributed computing

NASA Astrophysics Data System (ADS)

De, K.; Klimentov, A.; Maeno, T.; Nilsson, P.; Oleynik, D.; Panitkin, S.; Petrosyan, A.; Schovancova, J.; Vaniachine, A.; Wenaus, T.

2015-12-01

Experiments at the Large Hadron Collider (LHC) face unprecedented computing challenges. Heterogeneous resources are distributed worldwide at hundreds of sites, thousands of physicists analyse the data remotely, the volume of processed data is beyond the exabyte scale, while data processing requires more than a few billion hours of computing usage per year. The PanDA (Production and Distributed Analysis) system was developed to meet the scale and complexity of LHC distributed computing for the ATLAS experiment. In the process, the old batch job paradigm of locally managed computing in HEP was discarded in favour of a far more automated, flexible and scalable model. The success of PanDA in ATLAS is leading to widespread adoption and testing by other experiments. PanDA is the first exascale workload management system in HEP, already operating at more than a million computing jobs per day, and processing over an exabyte of data in 2013. There are many new challenges that PanDA will face in the near future, in addition to new challenges of scale, heterogeneity and increasing user base. PanDA will need to handle rapidly changing computing infrastructure, will require factorization of code for easier deployment, will need to incorporate additional information sources including network metrics in decision making, be able to control network circuits, handle dynamically sized workload processing, provide improved visualization, and face many other challenges. In this talk we will focus on the new features, planned or recently implemented, that are relevant to the next decade of distributed computing workload management using PanDA.

Feasibility and acceptability of a decision aid designed for people facing advanced or terminal illness: a pilot randomized trial.

PubMed

Matlock, Dan D; Keech, Tarah A E; McKenzie, Marlene B; Bronsert, Michael R; Nowels, Carolyn T; Kutner, Jean S

2014-02-01

Patients nearing the end of their lives face an array of difficult decisions. This study was designed to assess the feasibility and acceptability of a decision aid (DA) designed for patients facing advanced or terminal illness. We conducted a pilot randomized clinical trial of Health Dialog's Looking Ahead: choices for medical care when you're seriously ill DA (booklet and DVD) applied to patients on a hospital-based palliative care (PC) service. University of Colorado Hospital - December 2009 and May 2010. All adult, English-speaking patients or their decision makers were potentially eligible. Patients were not approached if they were in isolation, did not speak English or if any provider felt that they were not appropriate because of issues such as family conflict or actively dying. All participants received a standard PC consultation. Participants in the intervention arm also received a copy of the DA. Measurements Primary outcomes included decision conflict and knowledge. Participants in the intervention arm also completed an acceptability questionnaire and qualitative exit interviews. Of the 239 patients or decision makers, 51(21%) enrolled in the trial. The DA had no significant effect on decision conflict or knowledge. Exit interviews indicated it was acceptable and empowering, although they wished they had access to the DA earlier. While the DA was acceptable, feasibility was limited by late-life illness challenges. Future trials of this DA should be performed on patients earlier in their illness trajectory and should include additional outcome measures such as self-efficacy and confidence. © 2011 John Wiley & Sons Ltd.

Molecular composition and extinction coefficient of native botulinum neurotoxin complex produced by Clostridium botulinum hall A strain.

PubMed

Bryant, Anne-Marie; Davis, Jenny; Cai, Shuowei; Singh, Bal Ram

2013-02-01

Seven distinct strains of Clostridium botulinum (type A to G) each produce a stable complex of botulinum neurotoxin (BoNT) along with neurotoxin-associated proteins (NAPs). Type A botulinum neurotoxin (BoNT/A) is produced with a group of NAPs and is commercially available for the treatment of numerous neuromuscular disorders and cosmetic purposes. Previous studies have indicated that BoNT/A complex composition is specific to the strain, the method of growth and the method of purification; consequently, any variation in composition of NAPs could have significant implications to the effectiveness of BoNT based therapeutics. In this study, a standard analytical technique using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and densitometry analysis was developed to accurately analyze BoNT/A complex from C. botulinum type A Hall strain. Using 3 batches of BoNT/A complex the molar ratio was determined as neurotoxin binding protein (NBP, 124 kDa), heavy chain (HC, 90 kDa), light chain (LC, 53 kDa), NAP-53 (50 kDa), NAP-33 (36 kDa), NAP-22 (24 kDa), NAP-17 (17 kDa) 1:1:1:2:3:2:2. With Bradford, Lowry, bicinchoninic acid (BCA) and spectroscopic protein estimation methods, the extinction coefficient of BoNT/A complex was determined as 1.54 ± 0.26 (mg/mL)(-1)cm(-1). These findings of a reproducible BoNT/A complex composition will aid in understanding the molecular structure and function of BoNT/A and NAPs.

Anti-MRSA malleable liposomes carrying chloramphenicol for ameliorating hair follicle targeting

PubMed Central

Sung, Calvin T; Weng, Yi-Han; Fang, Jia-You

2017-01-01

Pathogens usually invade hair follicles when skin infection occurs. The accumulated bacteria in follicles are difficult to eradicate. The present study aimed to assess the cutaneous and follicular delivery of chloramphenicol (Cm)-loaded liposomes and the antibacterial activity of these liposomes against methicillin-resistant Staphylococcus aureus (MRSA). Skin permeation was conducted by in vitro Franz diffusion cell. The anti-MRSA potential was checked using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), a well diffusion test, and intracellular MRSA killing. The classic, dimyristoylphosphatidylcholine (DMPC), and deoxycholic acid (DA) liposomes had a vesicle size of 98, 132, and 239 nm, respectively. The incorporation of DMPC or DA into the liposomes increased the bilayer fluidity. The malleable vesicles containing DMPC and DA showed increased follicular Cm uptake over the control solution by 1.5- and 2-fold, respectively. The MIC and MBC of DA liposomes loaded with Cm were 62.5 and 62.5–125 μg/mL, comparable to free Cm. An inhibition zone about 2-fold higher was achieved by DA liposomes as compared to the free control at a Cm dose of 0.5 mg/mL. DA liposomes also augmented antibacterial activity on keratinocyte-infected MRSA. The deformable liposomes had good biocompatibility against keratinocytes and neutrophils (viability >80%). In vivo administration demonstrated that DA liposomes caused negligible toxicity on the skin, based on physiological examination and histology. These data suggest the potential application of malleable liposomes for follicular targeting and the treatment of MRSA-infected dermatologic conditions. PMID:29184410

Classification and quantitation of milk powder by near-infrared spectroscopy and mutual information-based variable selection and partial least squares

NASA Astrophysics Data System (ADS)

Chen, Hui; Tan, Chao; Lin, Zan; Wu, Tong

2018-01-01

Milk is among the most popular nutrient source worldwide, which is of great interest due to its beneficial medicinal properties. The feasibility of the classification of milk powder samples with respect to their brands and the determination of protein concentration is investigated by NIR spectroscopy along with chemometrics. Two datasets were prepared for experiment. One contains 179 samples of four brands for classification and the other contains 30 samples for quantitative analysis. Principal component analysis (PCA) was used for exploratory analysis. Based on an effective model-independent variable selection method, i.e., minimal-redundancy maximal-relevance (MRMR), only 18 variables were selected to construct a partial least-square discriminant analysis (PLS-DA) model. On the test set, the PLS-DA model based on the selected variable set was compared with the full-spectrum PLS-DA model, both of which achieved 100% accuracy. In quantitative analysis, the partial least-square regression (PLSR) model constructed by the selected subset of 260 variables outperforms significantly the full-spectrum model. It seems that the combination of NIR spectroscopy, MRMR and PLS-DA or PLSR is a powerful tool for classifying different brands of milk and determining the protein content.

Fully transparent, non-volatile bipolar resistive memory based on flexible copolyimide films

NASA Astrophysics Data System (ADS)

Yu, Hwan-Chul; Kim, Moon Young; Hong, Minki; Nam, Kiyong; Choi, Ju-Young; Lee, Kwang-Hun; Baeck, Kyoung Koo; Kim, Kyoung-Kook; Cho, Soohaeng; Chung, Chan-Moon

2017-01-01

Partially aliphatic homopolyimides and copolyimides were prepared from rel-(1'R,3S,5'S)-spiro[furan-3(2H),6'-[3]oxabicyclo[3.2.1]octane]-2,2',4',5(4H)-tetrone (DAn), 2,6-diaminoanthracene (AnDA), and 4,4'-oxydianiline (ODA) by varying the molar ratio of AnDA and ODA. We utilized these polyimide films as the resistive switching layer in transparent memory devices. While WORM memory behavior was obtained with the PI-A100-O0-based device (molar feed ratio of DAn : AnDA : ODA = 1 : 1 : 0), the PI-A70-O30-based device (molar feed ratio of DAn : AnDA : ODA = 1 : 0.7 : 0.3) exhibited bipolar resistive switching behavior with stable retention for 104 s. This result implies that the memory properties can be controlled by changing the polyimide composition. The two devices prepared from PI-A100-O0 and PI-A70-O30 showed over 90% transmittance in the visible wavelength range from 400 to 800 nm. The behavior of the memory devices is considered to be governed by trap-controlled, space-charge limited conduction (SCLC) and local filament formation. [Figure not available: see fulltext.

Genetic Dissection of Midbrain Dopamine Neuron Development in vivo

PubMed Central

Ellisor, Debra; Rieser, Caroline; Voelcker, Bettina; Machan, Jason T.; Zervas, Mark

2012-01-01

Midbrain dopamine (MbDA) neurons are partitioned into medial and lateral cohorts that control complex functions. However, the genetic underpinnings of MbDA neuron heterogeneity are unclear. While it is known that Wnt1-expressing progenitors contribute to MbDA neurons, the role of Wnt1 in MbDA neuron development in vivo is unresolved. We show that mice with a spontaneous point mutation in Wnt1 have a unique phenotype characterized by the loss of medial MbDA neurons concomitant with a severe depletion of Wnt1-expressing progenitors and diminished LMX1a-expressing progenitors. Wnt1 mutant embryos also have alterations in a hierarchical gene regulatory loop suggesting multiple gene involvement in the Wnt1 mutant MbDA neuron phenotype. To investigate this possibility, we conditionally deleted Gbx2, Fgf8, and En1/2 after their early role in patterning and asked whether these genetic manipulations phenocopied the depletion of MbDA neurons in Wnt1 mutants. The conditional deletion of Gbx2 did not result in re-positioning or distribution of MbDA neurons. The temporal deletion of Fgf8 did not result in the loss of either LMX1a-expressing progenitors nor the initial population of differentiated MbDA neurons, but did result in a complete loss of MbDA neurons at later stages. The temporal deletion and species specific manipulation of En1/2 demonstrated a continued and species specific role of Engrailed genes in MbDA neuron development. Notably, our conditional deletion experiments revealed phenotypes dissimilar to Wnt1 mutants indicating the unique role of Wnt1 in MbDA neuron development. By placing Wnt1, Fgf8, and En1/2 in the context of their temporal requirement for MbDA neuron development, we further deciphered the developmental program underpinning MbDA neuron progenitors. PMID:23041116

D-amphetamine (A)-induced dopamine (DA) release is not strictly dependent on newly-synthesized transmitter

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

Parker, E.; Cubeddu, L.

1986-03-05

A is thought to exert its stimulant effects by releasing DA from a newly synthesized transmitter pool. This hypothesis was evaluated directly by measuring the basal efflux and electrically-evoked release of endogenous DA and dihydroxyphenylacetic acid (DOPAC). In striatal slices from reserpine-treated rabbits A increased DA efflux, reduced DOPAC efflux, and inhibited electrically-evoked /sup 3/H-ACh release in a concentration-dependent manner. These effects could not be mimicked by inhibition of neuronal uptake or MAO, but were blocked by inhibition of DA synthesis or neuronal uptake, and were potentiated by inhibition of MAO. In slices with intact vesicular transmitter stores A inducedmore » DA efflux was 2-fold greater than that seen in slices having no vesicular stores. Inhibition of DA synthesis reduced A-induced DA efflux by 60%, but had little effect on the ability of A to inhibit /sup 3/H-ACh release. A also increased the electrical stimulation-evoked overflow of DA (an effect which was attenuated slightly by synthesis inhibition), and potently inhibited DOPAC overflow. These results suggest that: 1) A facilitates efflux of axoplasmic DA by an accelerated exchange diffusion mechanism. The releasable axoplasmic pool is derived from newly synthesized and vesicular transmitter pools; 2) postsynaptic indices of transmitter release may be misleading; and 3) A increases electrically-evoked DA release possibly by inhibiting neuronal uptake.« less

Dehydroandrographolide, an iNOS inhibitor, extracted from Andrographis paniculata (Burm.f.) Nees, induces autophagy in human oral cancer cells.

PubMed

Hsieh, Ming-Ju; Lin, Chiao-Wen; Chiou, Hui-Ling; Yang, Shun-Fa; Chen, Mu-Kuan

2015-10-13

Autophagy, which is constitutively executed at the basal level in all cells, promotes cellular homeostasis by regulating the turnover of organelles and proteins. Andrographolide and dehydroandrographolide (DA) are the two principle components of Andrographis paniculata (Burm.f.) Nees. and are the main contributors to its therapeutic properties. However, the pharmacological activities of dehydroandrographolide (DA) remain unclear. In this study, DA induces oral cancer cell death by activating autophagy. Treatment with autophagy inhibitors inhibited DA-induced human oral cancer cell death. In addition, DA increased LC3-II expression and reduced p53 expression in a time- and concentration-dependent manner. Furthermore, DA induced autophagy and decreased cell viability through modulation of p53 expression. DA-induced autophagy was triggered by an activation of JNK1/2 and an inhibition of Akt and p38. In conclusion, this study demonstrated that DA induced autophagy in human oral cancer cells by modulating p53 expression, activating JNK1/2, and inhibiting Akt and p38. Finally, an administration of DA effectively suppressed the tumor formation in the oral carcinoma xenograft model in vivo. This is the first study to reveal the novel function of DA in activating autophagy, suggesting that DA could serve as a new and potential chemopreventive agent for treating human oral cancer.

Dehydroandrographolide, an iNOS inhibitor, extracted from from Andrographis paniculata (Burm.f.) Nees, induces autophagy in human oral cancer cells

PubMed Central

Hsieh, Ming-Ju; Lin, Chiao-Wen; Chiou, Hui-Ling; Yang, Shun-Fa; Chen, Mu-Kuan

2015-01-01

Autophagy, which is constitutively executed at the basal level in all cells, promotes cellular homeostasis by regulating the turnover of organelles and proteins. Andrographolide and dehydroandrographolide (DA) are the two principle components of Andrographis paniculata (Burm.f.) Nees. and are the main contributors to its therapeutic properties. However, the pharmacological activities of dehydroandrographolide (DA) remain unclear. In this study, DA induces oral cancer cell death by activating autophagy. Treatment with autophagy inhibitors inhibited DA-induced human oral cancer cell death. In addition, DA increased LC3-II expression and reduced p53 expression in a time- and concentration-dependent manner. Furthermore, DA induced autophagy and decreased cell viability through modulation of p53 expression. DA-induced autophagy was triggered by an activation of JNK1/2 and an inhibition of Akt and p38. In conclusion, this study demonstrated that DA induced autophagy in human oral cancer cells by modulating p53 expression, activating JNK1/2, and inhibiting Akt and p38. Finally, an administration of DA effectively suppressed the tumor formation in the oral carcinoma xenograft model in vivo. This is the first study to reveal the novel function of DA in activating autophagy, suggesting that DA could serve as a new and potential chemopreventive agent for treating human oral cancer. PMID:26356821

Apoptosis of lactotrophs induced by D2 receptor activation is estrogen dependent.

PubMed

Radl, Daniela B; Zárate, Sandra; Jaita, Gabriela; Ferraris, Jimena; Zaldivar, Verónica; Eijo, Guadalupe; Seilicovich, Adriana; Pisera, Daniel

2008-01-01

Dopamine (DA) inhibits prolactin release and reduces lactotroph proliferation by activating D2 receptors. DA and its metabolite, 6-hydroxydopamine (6-OHDA), induce apoptosis in different cell types. DA receptors and DA transporter (DAT) were implicated in this action. Considering that estradiol sensitizes anterior pituitary cells to proapoptotic stimuli, we investigated the effect of estradiol on the apoptotic action of DA and 6-OHDA in anterior pituitary cells, and the involvement of the D2 receptor and DAT in the proapoptotic effect of DA. Viability of cultured anterior pituitary cells from ovariectomized rats was determined by MTS assay. Apoptosis was evaluated by Annexin-V/flow cytometry and TUNEL. Lactotrophs were identified by immunocytochemistry. DA induced apoptosis of lactotrophs in an estrogen-dependent manner. In contrast, estradiol was not required to trigger the apoptotic action of 6-OHDA. Cabergoline, a D2 receptor agonist, induced lactotroph apoptosis, while sulpiride, a D2 receptor antagonist, blocked DA-induced cell death. The blockade of DAT by GBR12909 did not affect the apoptotic action of DA, but inhibited 6-OHDA-induced apoptosis. These data show that DA, through D2 receptor activation, induces apoptosis of estrogen-sensitized anterior pituitary cells, and suggest that DA contributes to the control of lactotroph number not only by inhibiting proliferation but also by inducing apoptosis. 2008 S. Karger AG, Basel.

Enhanced dopamine detection sensitivity by PEDOT/graphene oxide coating on in vivo carbon fiber electrodes.

PubMed

Taylor, I Mitch; Robbins, Elaine M; Catt, Kasey A; Cody, Patrick A; Happe, Cassandra L; Cui, Xinyan Tracy

2017-03-15

Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA's oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Possibility of the transformation of eEF-2 (100 kDa) to eEF-2 (65 kDa) in the peptide elongation process in vitro.

PubMed

Gajko, A; Sredzińska, K; Galasiński, W; Gindzieński, A

1999-02-16

Two active eEF-2 polypeptides of approximately 100 and 65 kDa were copurified from rat liver cells and separated. The fate of eEF-2 (100 kDa) during its binding to ribosomes and in the translocation step of the peptide elongation process was investigated. It was shown that eEF-2 (100 kDa) did not change its form during the process of binding to the ribosomes. In the postribosomal supernatant, obtained from the postincubation mixture of the elongation process, only eEF-2 (65 kDa) was found. These results suggest that the form of eEF-2 (100 kDa), when bound to the ribosome during the elongation process, is transformed to eEF-2 (65 kDa). Copyright 1999 Academic Press.

Tryptic digestion of human GPIIIa. Isolation and biochemical characterization of the 23 kDa N-terminal glycopeptide carrying the antigenic determinant for a monoclonal antibody (P37) which inhibits platelet aggregation.

PubMed Central

Calvete, J J; Rivas, G; Maruri, M; Alvarez, M V; McGregor, J L; Hew, C L; Gonzalez-Rodriguez, J

1988-01-01

Early digestion of pure human platelet glycoprotein IIIa (GPIIIa) leads to a single cleavage of the molecule at 23 kDa far from one of the terminal amino acids. Automated Edman degradation demonstrates that GPIIIa and the smaller (23 kDa) tryptic fragment share the same N-terminal amino acid sequence. A further cleavage occurs in the larger fragment (80 kDa), reducing its apparent molecular mass by 10 kDa. The 23 kDa fragment remains attached to the larger ones in unreduced samples. Stepwise reduction of early digested GPIIIa with dithioerythritol selectively reduces the single disulphide bond joining the smaller (23 kDa) to the larger (80/70 kDa) fragments. Two fractions were obtained by size-exclusion chromatography of early digested GPIIIa after partial or full reduction and alkylation. The larger-size fraction contains the 80/70 kDa fragments, while the 23 kDa fragment is isolated in the smaller. The amino acid compositions of these fractions do not differ very significantly from the composition of GPIIIa; however the 23 kDa fragment contains only 10.2% by weight of sugars and is richer in neuraminic acid. Disulphide bonds are distributed four in the 23 kDa glycopeptide and 20-21 in the 80/70 kDa glycopeptide. The epitope for P37, a monoclonal antibody which inhibits platelet aggregation [Melero & González-Rodríguez (1984) Eur. J. Biochem. 141, 421-427] is situated within the first 17 kDa of the N-terminal region of GPIIIa, which gives a special functional interest to this extracellular region of GPIIIa. On the other hand, the epitopes for GPIIIa-specific monoclonal antibodies, P6, P35, P40 and P97, which do not interfere with platelet aggregation, are located within the larger tryptic fragment (80/70 kDa). Thus, the antigenic areas available in the extracellular surface of GPIIIa for these five monoclonal antibodies are now more precisely delineated. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2455507

Venom Proteomics of Indonesian King Cobra, Ophiophagus hannah: Integrating Top-Down and Bottom-Up Approaches.

PubMed

Petras, Daniel; Heiss, Paul; Süssmuth, Roderich D; Calvete, Juan J

2015-06-05

We report on the first application of top-down mass spectrometry in snake venomics. De novo sequence tags generated by, and ProSight Lite supported analysis of, combined collisional based dissotiations (CID and HCD) recorded in a hybrid LTQ Orbitrap instrument in data-dependent mode identified a number of proteins from different toxin families, namely, 11 three-finger toxins (7-7.9 kDa), a Kunitz-type inhibitor (6.3 kDa), ohanin (11.9 kDa), a novel phospholipase A2 molecule (13.8 kDa), and the cysteine-rich secretory protein (CRISP) ophanin (25 kDa) from Indonesian king cobra venom. Complementary bottom-up MS/MS analyses contributed to the completion of a locus-resolved venom phenotypic map for Ophiophagus hannah, the world's longest venomous snake and a species of medical concern across its wide distribution range in forests from India to Southeast Asia. Its venom composition, comprising 32-35 proteins/peptides from 10 protein families, is dominated by α-neurotoxins and convincingly explains the main neurotoxic effects of human envenoming caused by king cobra bite. The integration of efficient chromatographic separation of the venom's components and locus-resolved toxin identification through top-down and bottom-up MS/MS-based species-specific database searching and de novo sequencing holds promise that the future will be bright for the field of venom research.

Photoreceptive oscillators within neurons of the premammillary nucleus (PMM) and seasonal reproduction in temperate zone birds.

PubMed

Kosonsiriluk, Sunantha; Mauro, Laura J; Chaiworakul, Voravasa; Chaiseha, Yupaporn; El Halawani, Mohamed E

2013-09-01

The pathway for light transmission regulating the reproductive neuroendocrine system in temperate zone birds remains elusive. Based on the evidence provided from our studies with female turkeys, it is suggested that the circadian clock regulating reproductive seasonality is located in putatively photosensitive dopamine-melatonin (DA-MEL) neurons residing in the premammillary nucleus (PMM) of the caudal hypothalamus. Melanopsin is expressed by these neurons; a known photopigment which mediates light information pertaining to the entrainment of the clock. Exposure to a gonad stimulatory photoperiod enhances the activity of the DAergic system within DA-MEL neurons. DAergic activity encoding the light information is transmitted to the pars tuberalis, where thyroid-stimulating hormone, beta (TSHβ) cells reside, and induces the release of TSH. TSH stimulates tanycytes lining the base of the third ventricle and activates type 2 deiodinase in the ependymal which enhances triiodothyronine (T3) synthesis. T3 facilitates the release of gonadotropin-releasing hormone-I which stimulates luteinizing hormone/follicle stimulating hormone release and gonad recrudescence. These data taken together with the findings that clock genes are rhythmically expressed in the PMM where DA-MEL neurons are localized imply that endogenous oscillators containing photoreceptors within DA-MEL neurons are important in regulating the DA and MEL rhythms that drive the circadian cycle controlling seasonal reproduction. Published by Elsevier Inc.

Heterotetrameric composition of aquaporin-4 water channels.

PubMed

Neely, J D; Christensen, B M; Nielsen, S; Agre, P

1999-08-24

Aquaporin (AQP) water channel proteins are tetrameric assemblies of individually active approximately 30 kDa subunits. AQP4 is the predominant water channel protein in brain, but immunoblotting of native tissues has previously yielded multiple poorly resolved bands. AQP4 is known to encode two distinct mRNAs with different translation initiating methionines, M1 or M23. Using SDS-PAGE urea gels and immunoblotting with anti-peptide antibodies, four polypeptides were identified in brain and multiple other rat tissues with the following levels of expression: 32 kDa > 34 kDa > 36 kDa > 38 kDa. The 34 and 38 kDa polypeptides react with an antibody specific for the N-terminus of the M1 isoform, and 32 and 36 kDa correspond to the shorter M23 isoform. Immunogold electron microscopic studies with rat cerebellum cryosections demonstrated that the 34 kDa polypeptide colocalizes in perivascular astrocyte endfeet where the 32 kDa polypeptide is abundantly expressed. Velocity sedimentation, cross-linking, and immunoprecipitation analyses of detergent-solubilized rat brain revealed that the 32 and 34 kDa polypeptides reside within heterotetramers. Immunoprecipitation of AQP4 expressed in Xenopus laevis oocytes demonstrated that heterotetramer formation reflects the relative expression levels of the 32 and 34 kDa polypeptides; however, tetramers containing different compositions of the two polypeptides exhibit similar water permeabilities. These studies demonstrate that AQP4 heterotetramers are formed from two overlapping polypeptides and indicate that the 22-amino acid sequence at the N-terminus of the 34 kDa polypeptide does not influence water permeability but may contribute to membrane trafficking or assembly of arrays.

Oleic Acid in the Ventral Tegmental Area Inhibits Feeding, Food Reward, and Dopamine Tone.

PubMed

Hryhorczuk, Cecile; Sheng, Zhenyu; Décarie-Spain, Léa; Giguère, Nicolas; Ducrot, Charles; Trudeau, Louis-Éric; Routh, Vanessa H; Alquier, Thierry; Fulton, Stephanie

2018-02-01

Long-chain fatty acids (FAs) act centrally to decrease food intake and hepatic glucose production and alter hypothalamic neuronal activity in a manner that depends on FA type and cellular transport proteins. However, it is not known whether FAs are sensed by ventral tegmental area (VTA) dopamine (DA) neurons to control food-motivated behavior and DA neurotransmission. We investigated the impact of the monounsaturated FA oleate in the VTA on feeding, locomotion, food reward, and DA neuronal activity and DA neuron expression of FA-handling proteins and FA uptake. A single intra-VTA injection of oleate, but not of the saturated FA palmitate, decreased food intake and increased locomotor activity. Furthermore, intra-VTA oleate blunted the rewarding effects of high-fat/sugar food in an operant task and inhibited DA neuronal firing. Using sorted DA neuron preparations from TH-eGFP mice we found that DA neurons express FA transporter and binding proteins, and are capable of intracellular transport of long-chain FA. Finally, we demonstrate that a transporter blocker attenuates FA uptake into DA neurons and blocks the effects of intra-VTA oleate to decrease food-seeking and DA neuronal activity. Together, these results suggest that DA neurons detect FA and that oleate has actions in the VTA to suppress DA neuronal activity and food seeking following cellular incorporation. These findings highlight the capacity of DA neurons to act as metabolic sensors by responding not only to hormones but also to FA nutrient signals to modulate food-directed behavior.

Concentration-dependent activation of dopamine receptors differentially modulates GABA release onto orexin neurons

PubMed Central

Linehan, Victoria; Trask, Robert B.; Briggs, Chantalle; Rowe, Todd M.; Hirasawa, Michiru

2017-01-01

Dopamine (DA) and orexin neurons play important roles in reward and food intake. There are anatomical and functional connections between these two cell groups, where orexin peptides stimulate DA neurons in the ventral tegmental area and DA inhibits orexin neurons in the hypothalamus. However, the cellular mechanisms underlying DA action on orexin neurons remain incompletely understood. Therefore, the effect of DA on inhibitory transmission to orexin neurons was investigated in rat brain slices using whole cell patch clamp technique. We found that DA modulated the frequency of spontaneous and miniature IPSCs (mIPSCs) in a concentration dependent, bidirectional manner. Low (1 μM) and high concentrations (100 μM) of DA decreased and increased IPSC frequency, respectively. These effects did not accompany a change in mIPSC amplitude and persisted in the presence of G protein signaling inhibitor GDPβS in the pipette, suggesting that DA acts presynaptically. The decrease in mIPSC frequency was mediated by D2 receptors, whereas the increase required co-activation of D1 and D2 receptors and subsequent activation of phospholipase C. In summary, our results suggest that DA has complex effects on GABAergic transmission to orexin neurons, involving cooperation of multiple receptor subtypes. The direction of dopaminergic influence on orexin neurons is dependent on the level of DA in the hypothalamus. At low levels DA disinhibits orexin neurons whereas at high levels it facilitates GABA release, which may act as negative feedback to curb the excitatory orexinergic output to DA neurons. These mechanisms may have implications for consummatory and motivated behaviours. PMID:26036709

Age, period and cohort trends in drug abuse hospitalizations within the total Swedish population (1975-2010)*

PubMed Central

Giordano, Giuseppe N.; Ohlsson, Henrik; Kendler, Kenneth S.; Winkleby, Marilyn A.; Sundquist, Kristina; Sundquist, Jan

2014-01-01

Background: The societal consequences of drug abuse (DA) are severe and well documented, the World Health Organization recommending tracking of population trends for effective policy responses in treatment of DA and delivery of health care services. However, to correctly identify possible sources of DA change, one must first disentangle three different time-related influences on the need for treatment due to DA: age effects, period effects and cohort effects. Methods: We constructed our main Swedish national DA database (spanning four decades) by linking healthcare data from the Swedish Hospital Discharge Register to individuals, which included hospitalisations in Sweden for 1975-2010. All hospitalized DA cases were identified by ICD codes. Our Swedish national sample consisted of 3,078,129 men and 2,921,816 women. We employed a cross-classified multilevel logistic regression model to disentangle any net age, period and cohort effects on DA hospitalization rates. Results: We found distinct net age, period and cohort effects, each influencing the predicted probability ofhospitalisation for DA in men and women. Peak age for DA in both sexes was 33-35 years; net period effects showed an increase in hospitalisation for DA from 1996 to 2001; and in birth cohorts 1968-74, we saw a considerable reduction (around 75%) in predicted probability of hospitalisation for DA. Conclusions: The use of hospital admissions could be regarded as a proxy of the population's health service use for DA. Our results may thus constitute a basis for effective prevention planning, treatment and other appropriate policy responses. PMID:24300899

China’s Relations with Portuguese-speaking Countries: A Growing but Unnoticed Relation

DTIC Science & Technology

2012-09-01

Brazil and China Expand Satellite Program and African Countries Receive data from CBERS) Ministerio da Ciencia e Tecnologia do Brasil (Brazilian Ministry...Washington D.C. Ministerio da Ciencia e Tecnologia do Brasil (Brazilian Ministry of Science and Technology). “Brasil e China Ampliao Base do Programa CBERS

Dopamine modulation of emotional processing in cortical and subcortical neural circuits: evidence for a final common pathway in schizophrenia?

PubMed

Laviolette, Steven R

2007-07-01

The neural regulation of emotional perception, learning, and memory is essential for normal behavioral and cognitive functioning. Many of the symptoms displayed by individuals with schizophrenia may arise from fundamental disturbances in the ability to accurately process emotionally salient sensory information. The neurotransmitter dopamine (DA) and its ability to modulate neural regions involved in emotional learning, perception, and memory formation has received considerable research attention as a potential final common pathway to account for the aberrant emotional regulation and psychosis present in the schizophrenic syndrome. Evidence from both human neuroimaging studies and animal-based research using neurodevelopmental, behavioral, and electrophysiological techniques have implicated the mesocorticolimbic DA circuit as a crucial system for the encoding and expression of emotionally salient learning and memory formation. While many theories have examined the cortical-subcortical interactions between prefrontal cortical regions and subcortical DA substrates, many questions remain as to how DA may control emotional perception and learning and how disturbances linked to DA abnormalities may underlie the disturbed emotional processing in schizophrenia. Beyond the mesolimbic DA system, increasing evidence points to the amygdala-prefrontal cortical circuit as an important processor of emotionally salient information and how neurodevelopmental perturbances within this circuitry may lead to dysregulation of DAergic modulation of emotional processing and learning along this cortical-subcortical emotional processing circuit.

Fostering Informed Decisions: Impact of a Decision Aid Among Men Registered to Undergo Mass Screening for Prostate Cancer in a Randomized Controlled Trial

PubMed Central

Williams, Randi M.; Davis, Kimberly M.; Luta, George; Edmond, Sara N.; Dorfman, Caroline S.; Schwartz, Marc D.; Lynch, John; Ahaghotu, Chiledum; Taylor, Kathryn L.

2013-01-01

Objective Screening asymptomatic men for prostate cancer is controversial and informed decision making is recommended. Within two prostate cancer screening programs, we evaluated the impact of a print-based decision aid (DA) on decision-making outcomes. Methods Men (N=543) were 54.9 (SD=8.1) years old and 61% were African-American. The 2 (booklet type: DA vs. usual care (UC)) × 2 (delivery mode: Home vs. Clinic) randomized controlled trial assessed decisional and screening outcomes at baseline, two-months, and 13-months. Results Intention-to-treat linear regression analyses using generalized estimating equations revealed that DA participants reported improved knowledge relative to UC (B=.41, p<.05). For decisional conflict, per-protocol analyses revealed a group by time interaction (B = −.69, p<.05), indicating that DA participants were less likely to report decisional conflict at two-months compared to UC participants (OR=.49, 95% CI: .26–.91, p<.05). Conclusion This is the first randomized trial to evaluate a DA in the context of free mass screening, a challenging setting in which to make an informed decision. The DA was highly utilized by participants, improved knowledge and reduced decisional conflict. Practice implications These results are valuable in understanding ways to improve the decisions of men who seek screening and can be easily implemented within many settings. PMID:23357414

The Asymmetrical Effects of Divided Attention on Encoding and Retrieval Processes: A Different View Based on an Interference with the Episodic Register

PubMed Central

Guez, Jonathan; Naveh-Benjamin, Moshe

2013-01-01

In this study, we evaluate the conceptualization of encoding and retrieval processes established in previous studies that used a divided attention (DA) paradigm. These studies indicated that there were considerable detrimental effects of DA at encoding on later memory performance, but only minimal effects, if any, on divided attention at retrieval. We suggest that this asymmetry in the effects of DA on memory can be due, at least partially, to a confound between the memory phase (encoding and retrieval) and the memory requirements of the task (memory “for” encoded information versus memory “at” test). To control for this confound, we tested memory for encoded information and for retrieved information by introducing a second test that assessed memory for the retrieved information from the first test. We report the results of four experiments that use measures of memory performance, retrieval latency, and performance on the concurrent task, all of which consistently show that DA at retrieval strongly disrupts later memory for the retrieved episode, similarly to the effects of DA at encoding. We suggest that these symmetrical disruptive effects of DA at encoding and retrieval on later retrieval reflect a disruption of an episodic buffer (EB) or episodic register component (ER), rather than a failure of encoding or retrieval operations per se. PMID:24040249

Simultaneous determination of ascorbic acid, dopamine and uric acid based on tryptophan functionalized graphene.

PubMed

Lian, Qianwen; He, Zhifang; He, Qian; Luo, Ai; Yan, Kaiwang; Zhang, Dongxia; Lu, Xiaoquan; Zhou, Xibin

2014-05-01

A new type of tryptophan-functionalized graphene nanocomposite (Trp-GR) was synthesized by utilizing a facile ultrasonic method via π-π conjugate action between graphene (GR) and tryptophan (Trp) molecule. The material as prepared had well dispersivity in water and better conductivity than pure GR. The surface morphology of Trp-GR was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Raman spectroscopy. The electrochemical behaviors of ascorbic acid (AA), dopamine (DA), and uric acid (UA) were investigated by cyclic voltammetry (CV) on the surface of Trp-GR. The separation of the oxidation peak potentials for AA-DA, DA-UA and UA-AA was about 182 mV, 125 mV and 307 mV, which allowed simultaneously determining AA, DA, and UA. Differential pulse voltammetery (DPV) was used for the determination of AA, DA, and UA in their mixture. Under optimum conditions, the linear response ranges for the determination of AA, DA, and UA were 0.2-12.9 mM, 0.5-110 μM, and 10-1000 μM, with the detection limits (S/N=3) of 10.09 μM, 0.29 μM and 1.24 μM, respectively. Furthermore, the modified electrode was investigated for real sample analysis. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Dopaminergic Neurons Controlling Anterior Pituitary Functions: Anatomy and Ontogenesis in Zebrafish.

PubMed

Fontaine, Romain; Affaticati, Pierre; Bureau, Charlotte; Colin, Ingrid; Demarque, Michaël; Dufour, Sylvie; Vernier, Philippe; Yamamoto, Kei; Pasqualini, Catherine

2015-08-01

Dopaminergic (DA) neurons located in the preoptico-hypothalamic region of the brain exert a major neuroendocrine control on reproduction, growth, and homeostasis by regulating the secretion of anterior pituitary (or adenohypophysis) hormones. Here, using a retrograde tract tracing experiment, we identified the neurons playing this role in the zebrafish. The DA cells projecting directly to the anterior pituitary are localized in the most anteroventral part of the preoptic area, and we named them preoptico-hypophyseal DA (POHDA) neurons. During development, these neurons do not appear before 72 hours postfertilization (hpf) and are the last dopaminergic cell group to differentiate. We found that the number of neurons in this cell population continues to increase throughout life proportionally to the growth of the fish. 5-Bromo-2'-deoxyuridine incorporation analysis suggested that this increase is due to continuous neurogenesis and not due to a phenotypic change in already-existing neurons. Finally, expression profiles of several genes (foxg1a, dlx2a, and nr4a2a/b) were different in the POHDA compared with the adjacent suprachiasmatic DA neurons, suggesting that POHDA neurons develop as a distinct DA cell population in the preoptic area. This study offers some insights into the regional identity of the preoptic area and provides the first bases for future functional genetic studies on the development of DA neurons controlling anterior pituitary functions.

The asymmetrical effects of divided attention on encoding and retrieval processes: a different view based on an interference with the episodic register.

PubMed

Guez, Jonathan; Naveh-Benjamin, Moshe

2013-01-01

In this study, we evaluate the conceptualization of encoding and retrieval processes established in previous studies that used a divided attention (DA) paradigm. These studies indicated that there were considerable detrimental effects of DA at encoding on later memory performance, but only minimal effects, if any, on divided attention at retrieval. We suggest that this asymmetry in the effects of DA on memory can be due, at least partially, to a confound between the memory phase (encoding and retrieval) and the memory requirements of the task (memory "for" encoded information versus memory "at" test). To control for this confound, we tested memory for encoded information and for retrieved information by introducing a second test that assessed memory for the retrieved information from the first test. We report the results of four experiments that use measures of memory performance, retrieval latency, and performance on the concurrent task, all of which consistently show that DA at retrieval strongly disrupts later memory for the retrieved episode, similarly to the effects of DA at encoding. We suggest that these symmetrical disruptive effects of DA at encoding and retrieval on later retrieval reflect a disruption of an episodic buffer (EB) or episodic register component (ER), rather than a failure of encoding or retrieval operations per se.

Quantitative SERS Detection of Dopamine in Cerebrospinal Fluid by Dual-Recognition-Induced Hot Spot Generation.

PubMed

Zhang, Kun; Liu, Yu; Wang, Yuning; Zhang, Ren; Liu, Jiangang; Wei, Jia; Qian, Hufei; Qian, Kun; Chen, Ruoping; Liu, Baohong

2018-05-09

Reliable profiling of the extracellular dopamine (DA) concentration in the central nervous system is essential for a deep understanding of its biological and pathological functions. However, quantitative determination of this neurotransmitter remains a challenge because of the extremely low concentration of DA in the cerebrospinal fluid (CSF) of patients. Herein, on the basis of the specific recognition of boronate toward diol and N-hydroxysuccinimide ester toward the amine group, a simple and highly sensitive strategy was presented for DA detection by using surface-enhanced Raman scattering (SERS) spectroscopy as a signal readout. This was realized by first immobilizing 3,3'-dithiodipropionic acid di( N-hydroxysuccinimide ester) on gold thin film surfaces to capture DA, followed by introducing 3-mercaptophenylboronic acid (3-MPBA)-functionalized silver nanoparticles to generate numerous plasmonic "hot spots" with the nanoparticle-on-mirror geometry. Such a dual-recognition mechanism not only avoids complicated bioelement-based manipulations but also efficiently decreases the background signal. With the direct use of the recognition probe 3-MPBA as a Raman reporter, the "signal-on" SERS method was employed to quantify the concentration of DA from 1 pM to 1 μM with a detection limit of 0.3 pM. Moreover, our dual-recognition-directed SERS assay exhibited a high resistance to cerebral interference and was successfully applied to monitoring of DA in CSF samples of patients.

The Intermediate Luminosity Optical Transient SN 2010da: The Progenitor, Eruption, and Aftermath of a Peculiar Supergiant High-mass X-Ray Binary

NASA Astrophysics Data System (ADS)

Villar, V. A.; Berger, E.; Chornock, R.; Margutti, R.; Laskar, T.; Brown, P. J.; Blanchard, P. K.; Czekala, I.; Lunnan, R.; Reynolds, M. T.

2016-10-01

We present optical spectroscopy, ultraviolet-to-infrared imaging, and X-ray observations of the intermediate luminosity optical transient (ILOT) SN 2010da in NGC 300 (d = 1.86 Mpc) spanning from -6 to +6 years relative to the time of outburst in 2010. Based on the light-curve and multi-epoch spectral energy distributions of SN 2010da, we conclude that the progenitor of SN 2010da is a ≈10-12 M ⊙ yellow supergiant possibly transitioning into a blue-loop phase. During outburst, SN 2010da had a peak absolute magnitude of M bol ≲ -10.4 mag, dimmer than other ILOTs and supernova impostors. We detect multi-component hydrogen Balmer, Paschen, and Ca II emission lines in our high-resolution spectra, which indicate a dusty and complex circumstellar environment. Since the 2010 eruption, the star has brightened by a factor of ≈5 and remains highly variable in the optical. Furthermore, we detect SN 2010da in archival Swift and Chandra observations as an ultraluminous X-ray source (L X ≈ 6 × 1039 erg s-1). We additionally attribute He II 4686 Å and coronal Fe emission lines in addition to a steady X-ray luminosity of ≈1037 erg s-1 to the presence of a compact companion.

A facile approach to the isolation of proteins in Ferula asafoetida and their enzyme stabilizing, anti-microbial and anti-oxidant activity.

PubMed

Chandran, Sanjana; Sakthivel, Meenakumari; Thirumavalavan, Munusamy; Thota, Jagadeshwar Reddy; Mariappanadar, Vairamani; Raman, Pachaiappan

2017-09-01

The objective of the present study was to identify the proteome pattern, isolate and study the functions of selective proteins from Ferula asafoetida root exudate using chromatographic techniques. The root exudate proteins were fractionated using ion-exchange and gel filtration chromatography. A range of bioactive protein fractions were then separated in sufficient quantity which is the focus of this study. Based on studies, here we report three main proteins with molecular weights 14kDa, 27kDa, and 39kDa. The biological and pharmacological activities of both purified and unpurified proteins obtained were extensively studied to understand their significance. The study revelaed that 27kDa protein interestingly stabilized trypsin activity in 24h of time and retained about 64% of the enzyme activity. Analyses confirmed 40°C and pH 8.0 are the optimum temperature and pH respectively. The 39kDa protein remarkably increased the activity of chymotrypsin and the 14kDa protein showed anti-bacterial activity against Pseudomonas aeruginosa. Invariably all of the three purified proteins showed enhanced anti-oxidant activity. In conclusion, results here obtained suggested that the primary metabolites (proteins) in asafoetida are mainly responsible for its versatile biological and pharmacological activities. Copyright © 2017 Elsevier B.V. All rights reserved.

Agarose and Polyacrylamide Gel Electrophoresis Methods for Molecular Mass Analysis of 5–500 kDa Hyaluronan

PubMed Central

Bhilocha, Shardul; Amin, Ripal; Pandya, Monika; Yuan, Han; Tank, Mihir; LoBello, Jaclyn; Shytuhina, Anastasia; Wang, Wenlan; Wisniewski, Hans-Georg; de la Motte, Carol; Cowman, Mary K.

2011-01-01

Agarose and polyacrylamide gel electrophoresis systems for the molecular mass-dependent separation of hyaluronan (HA) in the size range of approximately 5–500 kDa have been investigated. For agarose-based systems, the suitability of different agarose types, agarose concentrations, and buffers systems were determined. Using chemoenzymatically synthesized HA standards of low polydispersity, the molecular mass range was determined for each gel composition, over which the relationship between HA mobility and logarithm of the molecular mass was linear. Excellent linear calibration was obtained for HA molecular mass as low as approximately 9 kDa in agarose gels. For higher resolution separation, and for extension to molecular masses as low as approximately 5 kDa, gradient polyacrylamide gels were superior. Densitometric scanning of stained gels allowed analysis of the range of molecular masses present in a sample, and calculation of weight-average and number-average values. The methods were validated for polydisperse HA samples with viscosity-average molecular masses of 112, 59, 37, and 22 kDa, at sample loads of 0.5 µg (for polyacrylamide) to 2.5 µg (for agarose). Use of the methods for electrophoretic mobility shift assays was demonstrated for binding of the HA-binding region of aggrecan (recombinant human aggrecan G1-IGD-G2 domains) to a 150 kDa HA standard. PMID:21684248

Persistent Adaptations in Afferents to Ventral Tegmental Dopamine Neurons after Opiate Withdrawal

PubMed Central

Kaufling, Jennifer

2015-01-01

Protracted opiate withdrawal is accompanied by altered responsiveness of midbrain dopaminergic (DA) neurons, including a loss of DA cell response to morphine, and by behavioral alterations, including affective disorders. GABAergic neurons in the tail of the ventral tegmental area (tVTA), also called the rostromedial tegmental nucleus, are important for behavioral responses to opiates. We investigated the tVTA–VTA circuit in rats after chronic morphine exposure to determine whether tVTA neurons participate in the loss of opiate-induced disinhibition of VTA DA neurons observed during protracted withdrawal. In vivo recording revealed that VTA DA neurons, but not tVTA GABAergic neurons, are tolerant to morphine after 2 weeks of withdrawal. Optogenetic stimulation of tVTA neurons inhibited VTA DA neurons similarly in opiate-naive and long-term withdrawn rats. However, tVTA inactivation increased VTA DA activity in opiate-naive rats, but not in withdrawn rats, resembling the opiate tolerance effect in DA cells. Thus, although inhibitory control of DA neurons by tVTA is maintained during protracted withdrawal, the capacity for disinhibitory control is impaired. In addition, morphine withdrawal reduced both tVTA neural activity and tonic glutamatergic input to VTA DA neurons. We propose that these changes in glutamate and GABA inputs underlie the apparent tolerance of VTA DA neurons to opiates after chronic exposure. These alterations in the tVTA–VTA DA circuit could be an important factor in opiate tolerance and addiction. Moreover, the capacity of the tVTA to inhibit, but not disinhibit, DA cells after chronic opiate exposure may contribute to long-term negative affective states during withdrawal. SIGNIFICANCE STATEMENT Dopaminergic (DA) cells of the ventral tegmental area (VTA) are the origin of a brain reward system and are critically involved in drug abuse. Morphine has long been known to affect VTA DA cells via GABAergic interneurons. Recently, GABAergic neurons caudal to the VTA were discovered and named the tail of VTA (tVTA). Here, we show that tVTA GABA neurons lose their capacity to disinhibit, but not to inhibit, VTA DA cells after chronic opiate exposure. The failure of disinhibition was associated with a loss of glutamatergic input to DA neurons after chronic morphine. These findings reveal mechanisms by which the tVTA may play a key role in long-term negative affective states during opiate withdrawal. PMID:26180204

Effect of gamma irradiation on the expressed proteins in the foodborne pathogen Staphylococcus aureus

NASA Astrophysics Data System (ADS)

Trudeau, Karine; Dang Vu, Khanh; Shareck, François; Lacroix, Monique

2012-08-01

A capillary electrophoresis method with UV detection was developed to analyze protein composition of the foodborne pathogen Staphylococcus aureus. Bacterial samples containing 109 CFU/ml, obtained after two cycles of incubations of 24 h, were gamma irradiated at different doses of 1.2, 3.5 and 2.9 kGy to respectively create damage cells, to kill cells and to provoke viable but non cultivable cells (VBNC). It was observed that an irradiation at a sensitive dose of 1.2 kGy caused a significantly increase in the protein with molecular weight (MW) of 17.7 kDa (from 0.61% to 1.2%). This treatment also caused decreases in the expressed proteins with the MWs of 16.3 kDa (from 6.2% to 5.3%) and of 23.4 kDa (from 4.0% to 2.30%). Irradiation at a VBCN dose of 2.9 kGy caused increases in expressed proteins with the MWs of 17.7 kDa (from 0.61% to 3.43%), 18.7 kDa (from 1.04% to 4.30%), 19.5 kDa (from 0.71% to 2.30%), 21.1 kDa (from 1.20% to 3.80%). Moreover, this treatment (2.9 kGy) also caused significantly decreases (P≤0.05) in the expressed proteins with the MW of 30.7 kDa (from 8.6% to 5.15%), 36.3 kDa (from 3.1% to 2.7%) and 40.5 kDa (from 11.3% to 8.5%). Finally, for the irradiation at a lethal dose of 3.5 kGy, it can be found that the expressed proteins with the MW of 17.7 kDa, 18.7 kDa and 19.5 kDa were increased less than that of expressed proteins at the VCNC dose (2.9 kGy) and these might be the very important proteins which are responsible for the survival of the S. aureus. Further, there were also the decreases in expressed proteins with the MW of 30.7 kDa, 36.3 kDa and 75.1 kDa at this dose of treatment (3.5 kGy) which can be expected that these proteins are seriously affected at high dose of γ-irradiation treatment.

TGF-β Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning.

PubMed

Luo, Sarah X; Timbang, Leah; Kim, Jae-Ick; Shang, Yulei; Sandoval, Kadellyn; Tang, Amy A; Whistler, Jennifer L; Ding, Jun B; Huang, Eric J

2016-12-20

Neural circuits involving midbrain dopaminergic (DA) neurons regulate reward and goal-directed behaviors. Although local GABAergic input is known to modulate DA circuits, the mechanism that controls excitatory/inhibitory synaptic balance in DA neurons remains unclear. Here, we show that DA neurons use autocrine transforming growth factor β (TGF-β) signaling to promote the growth of axons and dendrites. Surprisingly, removing TGF-β type II receptor in DA neurons also disrupts the balance in TGF-β1 expression in DA neurons and neighboring GABAergic neurons, which increases inhibitory input, reduces excitatory synaptic input, and alters phasic firing patterns in DA neurons. Mice lacking TGF-β signaling in DA neurons are hyperactive and exhibit inflexibility in relinquishing learned behaviors and re-establishing new stimulus-reward associations. These results support a role for TGF-β in regulating the delicate balance of excitatory/inhibitory synaptic input in local microcircuits involving DA and GABAergic neurons and its potential contributions to neuropsychiatric disorders. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Apomorphine and the dopamine hypothesis of schizophrenia: a dilemma?

PubMed Central

Dépatie, L; Lal, S

2001-01-01

The dopamine (DA) hypothesis of schizophrenia implicates an enhancement of DA function in the pathophysiology of the disorder, at least in the genesis of positive symptoms. Accordingly, apomorphine, a directly acting DA receptor agonist, should display psychotomimetic properties. A review of the literature shows little or no evidence that apomorphine, in doses that stimulate postsynaptic DA receptors, induces psychosis in non-schizophrenic subjects or a relapse or exacerbation of psychotic symptoms in patients with schizophrenia. After a detailed review of the literature reporting psychotogenic effects of apomorphine in patients with Parkinson's disease, an interpretation of these data is difficult, in part because of several confounding factors, such as the concomitant use of drugs known to induce psychosis and the advanced state of the progressive neurological disorder. In the context of the DA hypothesis of schizophrenia, the limited ability of apomorphine to induce psychosis, in contrast to indirectly acting DA agonists that increase synaptic DA, may be explained by the relatively weak affinity of apomorphine for the D3 receptor compared with DA. Alternatively, enhancement of DA function, though necessary, may be insufficient by itself to induce psychosis. PMID:11394190

Electrospray ionization mass analysis of normal and genetic variants of human serum albumin.

PubMed

Brennan, S O

1998-11-01

Both normal albumin (Al A) and genetically modified forms were isolated from six heterozygous subjects. Albumins from each individual were analyzed by electrospray ionization mass spectrometry (ESI MS), and the mass was compared with that predicted from the protein sequence. In all cases, the Al A was heterogeneous, with components of mass (+/- SE) 66463+/-4, 66586+/-3, and 66718+/-5 Da. Each genetic variant showed similar heterogeneity. The mass increase in Al Casebrook (2214 Da) was very close to that predicted (2205 Da) from protein and carbohydrate sequence analysis, whereas the increase in Al Redhill (2378 Da) was close to that expected (2392 Da) for an Arg-albumin with a disialylated N-linked biantennary oligosaccharide and an Ala-->Thr mutation. The circulating proalbumins, Christchurch and Blenheim, had mass increases of 748 and 756 Da, respectively, over Al A; in excellent agreement with theoretical values of 744 and 756. Clear shifts in mass were also detected for the point substitutions 177Cys-->Phe (44 Da), 1Asp-->Val (20 Da), and Arg-albumin (160 Da).

Development and validation of a Partial Least Squares-Discriminant Analysis (PLS-DA) model based on the determination of ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) in hair for the diagnosis of chronic alcohol abuse.

PubMed

Alladio, E; Giacomelli, L; Biosa, G; Corcia, D Di; Gerace, E; Salomone, A; Vincenti, M

2018-01-01

The chronic intake of an excessive amount of alcohol is currently ascertained by determining the concentration of direct alcohol metabolites in the hair samples of the alleged abusers, including ethyl glucuronide (EtG) and, less frequently, fatty acid ethyl esters (FAEEs). Indirect blood biomarkers of alcohol abuse are still determined to support hair EtG results and diagnose a consequent liver impairment. In the present study, the supporting role of hair FAEEs is compared with indirect blood biomarkers with respect to the contexts in which hair EtG interpretation is uncertain. Receiver Operating Characteristics (ROC) curves and multivariate Principal Component Analysis (PCA) demonstrated much stronger correlation of EtG results with FAEEs than with any single indirect biomarker or their combinations. Partial Least Squares Discriminant Analysis (PLS-DA) models based on hair EtG and FAEEs were developed to maximize the biomarkers information content on a multivariate background. The final PLS-DA model yielded 100% correct classification on a training/evaluation dataset of 155 subjects, including both chronic alcohol abusers and social drinkers. Then, the PLS-DA model was validated on an external dataset of 81 individual providing optimal discrimination ability between chronic alcohol abusers and social drinkers, in terms of specificity and sensitivity. The PLS-DA scores obtained for each subject, with respect to the PLS-DA model threshold that separates the probabilistic distributions for the two classes, furnished a likelihood ratio value, which in turn conveys the strength of the experimental data support to the classification decision, within a Bayesian logic. Typical boundary real cases from daily work are discussed, too. Copyright © 2017 Elsevier B.V. All rights reserved.

Involving women in personalised decision-making on mode of delivery after caesarean section: the development and pilot testing of a patient decision aid.

PubMed

Schoorel, E N C; Vankan, E; Scheepers, H C J; Augustijn, B C C; Dirksen, C D; de Koning, M; van Kuijk, S M J; Kwee, A; Melman, S; Nijhuis, J G; Aardenburg, R; de Boer, K; Hasaart, T H M; Mol, B W J; Nieuwenhuijze, M; van Pampus, M G; van Roosmalen, J; Roumen, F J M E; de Vries, R; Wouters, M G A J; van der Weijden, T; Hermens, R P M G

2014-01-01

To develop a patient decision aid (PtDA) for mode of delivery after caesarean section that integrates personalised prediction of vaginal birth after caesarean (VBAC) with the elicitation of patient preferences and evidence-based information. A PtDA was developed and pilot tested using the International Patients Decision Aid Standards (IPDAS) criteria. Obstetric health care in the Netherlands. A multidisciplinary steering group, an expert panel, and 25 future users of the PtDA, i.e. women with a previous caesarean section. The development consisted of a construction phase (definition of scope and purpose, and selection of content, framework, and format) and a pilot testing phase by interview. The process was supervised by a multidisciplinary steering group. Usability, clarity, and relevance. The construction phase resulted in a booklet including unbiased balanced information on mode of birth after caesarean section, a preference elicitation exercise, and tailored risk information, including a prediction model for successful VBAC. During pilot testing, visualisation of risks and clarity formed the main basis for revisions. Pilot testing showed the availability of tailored structured information to be the main factor involving women in decision-making. The PtDA meets 39 out of 50 IPDAS criteria (78%): 23 out of 23 criteria for content (100%) and 16 out of 20 criteria for the development process (80%). Criteria for effectiveness (n = 7) were not evaluated. An evidence-based PtDA was developed, with the probability of successful VBAC and the availability of structured information as key items. It is likely that the PtDA enhances the quality of decision-making on mode of birth after caesarean section. © 2013 Royal College of Obstetricians and Gynaecologists.

Dual-channel optical sensing platform for detection of diminazene aceturate based on thioglycolic acid-wrapped cadmium telluride/cadmium sulfide quantum dots.

PubMed

Hao, Chenxia; Zhou, Tao; Liu, Shaopu; Wang, Linlin; Huang, Bowen; Kuang, Nianxi; He, Youqiu

2016-06-15

A dual-channel optical sensing platform which combines the advantages of dual-wavelength overlapping resonance Rayleigh scattering (DWO-RRS) and fluorescence has been designed for the detection of diminazene aceturate (DA). It is based on the use of thioglycolic acid-wrapped CdTe/CdS quantum dots (Q-dots). In the absence of DA, the thioglycolic acid-wrapped CdTe/CdS Q-dots exhibit the high fluorescence spectrum and low RRS spectrum, so are selected to develop an easy-to-get system. In the presence of DA, the thioglycolic acid-wrapped CdTe/CdS Q-dots and DA form a complex through electrostatic interaction, which result in the RRS intensity getting enhanced significantly with new RRS peaks appearing at 317 and 397 nm; the fluorescence is powerfully quenched. Under optimum conditions, the scattering intensities of the two peaks are proportional to the concentration of DA in the range of 0.0061-3.0 μg mL(-1). The detection limits for the two single peaks are 4.1 ng mL(-1) and 3.3 ng mL(-1), while that of the DWO-RRS method is 1.8 ng mL(-1), indicating that the DWO-RRS method has high sensitivity. Besides, the fluorescence also exhibits good linear range from 0.0354 to 10.0 μg mL(-1) with a detection limit of 10.6 ng mL(-1). In addition, the system has been applied to the detection of DA in milk samples with satisfactory results. Copyright © 2016 Elsevier Inc. All rights reserved.

Self-assembled dopamine nanolayers wrapped carbon nanotubes as carbon-carbon bi-functional nanocatalyst for highly efficient oxygen reduction reaction and antiviral drug monitoring

NASA Astrophysics Data System (ADS)

Khalafallah, Diab; Akhtar, Naeem; Alothman, Othman Y.; Fouad, H.; Abdelrazek khalil, Khalil

2017-09-01

Oxygen reduction reaction (ORR) catalysts are the heart of eco-friendly energy resources particularly low temperature fuel cells. Although valuable efforts have been devoted to synthesize high performance catalysts for ORR, considerable challenges are extremely desirable in the development of energy technologies. Herein, we report a simple self-polymerization method to build a thin film of dopamine along the tubular nanostructures of multi-walled carbon nanotubes (CNT) in a weak alkaline solution. The dopamine@CNT hybrid (denoted as DA@CNT) reveals an enhanced electrocatalytic activity towards ORR with highly positive onset potential and cathodic current as a result of their outstanding features of longitudinal mesoporous structure, high surface area, and ornamentation of DA layers with nitrogen moieties, which enable fast electron transport and fully exposed electroactive sites. Impressively, the as-obtained hybrid afford remarkable electrochemical durability for prolonged test time of 60,000 s compared to benchmark Pt/C (20 wt%) catalyst. Furthermore, the developed DA@CNT electrode was successfully applied to access the quality of antiviral drug named Valacyclovir (VCR). The DA@CNT electrode shows enhanced sensing performance in terms of large linear range (3-75 nM), low limit of detection (2.55 nM) than CNT based electrode, indicating the effectiveness of the DA coating. Interestingly, the synergetic effect of nanostructured DA and CNT can significantly boost the electronic configuration and exposure level of active species for ORR and biomolecule recognition. Therefore, the existing carbon-based porous electrocatalyst may find numerous translational applications as attractive alternative to noble metals in polymer electrolyte membrane fuel cells and quality control assessment of pharmaceutical and therapeutic drugs.

Digital Architecture Planning Model

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

Oxstrand, Johanna Helene; Al Rashdan, Ahmad Yahya Mohammad; Bly, Aaron Douglas

As part of the U.S. Department of Energy’s Light Water Reactor Sustainability Program, the Digital Architecture (DA) Project focuses on providing a model that nuclear utilities can refer to when planning deployment of advanced technologies. The digital architecture planning model (DAPM) is the methodology for mapping power plant operational and support activities into a DA that unifies all data sources needed by the utilities to operate their plants. The DA is defined as a collection of information technology capabilities needed to support and integrate a wide spectrum of real-time digital capabilities for performance improvements of nuclear power plants. DA canmore » be thought of as integration of the separate instrumentation and control and information systems already in place in nuclear power plants, which are brought together for the purpose of creating new levels of automation in plant work activities. A major objective in DAPM development was to survey all key areas that needed to be reviewed in order for a utility to make knowledgeable decisions regarding needs and plans to implement a DA at the plant. The development was done in two steps. First, researchers surveyed the nuclear industry in order to learn their near-term plans for adopting new advanced capabilities and implementing a network (i.e., wireless and wire) infrastructure throughout the plant, including the power block. Secondly, a literature review covering regulatory documents, industry standards, and technical research reports and articles was conducted. The objective of the review was to identify key areas to be covered by the DAPM, which included the following: 1. The need for a DA and its benefits to the plant 2. Resources required to implement the DA 3. Challenges that need to be addressed and resolved to implement the DA 4. Roles and responsibilities of the DA implementation plan. The DAPM was developed based on results from the survey and the literature review. Model development, including the survey results and conclusions made about the key areas during the literature review, are described in this report.« less

Dynamic Assessment for 3- and 4-Year-Old Children Who Use Augmentative and Alternative Communication: Evaluating Expressive Syntax.

PubMed

Binger, Cathy; Kent-Walsh, Jennifer; King, Marika

2017-07-12

The developmental readiness to produce early sentences with an iPad communication application was assessed with ten 3- and 4-year-old children with severe speech disorders using graduated prompting dynamic assessment (DA) techniques. The participants' changes in performance within the DA sessions were evaluated, and DA performance was compared with performance during a subsequent intervention. Descriptive statistics were used to examine patterns of performance at various cueing levels and mean levels of cueing support. The Wilcoxon signed-ranks test was used to measure changes within the DA sessions. Correlational data were calculated to determine how well performance in DA predicted performance during a subsequent intervention. Participants produced targets successfully in DA at various cueing levels, with some targets requiring less cueing than others. Performance improved significantly within the DA sessions-that is, the level of cueing required for accurate productions of the targets decreased during DA sessions. Last, moderate correlations existed between DA scores and performance during the intervention for 3 out of 4 targets, with statistically significant findings for 2 of 4 targets. DA offers promise for examining the developmental readiness of young children who use augmentative and alternative communication to produce early expressive language structures.

Developmental analysis of the dopamine-containing neurons of the Drosophila brain

PubMed Central

Hartenstein, Volker; Cruz, Louie; Lovick, Jennifer K.; Guo, Ming

2016-01-01

The Drosophila dopaminergic (DA) system consists of a relatively small number of neurons clustered throughout the brain and ventral nerve cord. Previous work shows that clusters of DA neurons innervate different brain compartments, which in part accounts for functional diversity of the DA system. In this paper, we analyzed the association between DA neuron clusters and specific brain lineages, developmental and structural units of the Drosophila brain which provide a framework of connections that can be followed throughout development. The hatching larval brain contains six groups of primary DA neurons (born in the embryo), which we assign to six distinct lineages. We can show that all larval DA clusters persist into the adult brain. Some clusters increase in cell number during late larval stages while others do not become DA-positive until early pupa. Ablating neuroblasts with hydroxyurea (HU) prior to onset of larval proliferation (generates secondary neurons) confirms these added DA clusters are primary neurons born in the embryo, rather than secondary neurons. A single cluster that becomes DA-positive in the late pupa, PAM1/lineage DALcm1/2, forms part of a secondary lineage which can be ablated by larval HU application. By supplying lineage information for each DA cluster, our analysis promotes further developmental and functional analyses of this important system of neurons. PMID:27350102

Evolution of the ATLAS PanDA workload management system for exascale computational science

NASA Astrophysics Data System (ADS)

Maeno, T.; De, K.; Klimentov, A.; Nilsson, P.; Oleynik, D.; Panitkin, S.; Petrosyan, A.; Schovancova, J.; Vaniachine, A.; Wenaus, T.; Yu, D.; Atlas Collaboration

2014-06-01

An important foundation underlying the impressive success of data processing and analysis in the ATLAS experiment [1] at the LHC [2] is the Production and Distributed Analysis (PanDA) workload management system [3]. PanDA was designed specifically for ATLAS and proved to be highly successful in meeting all the distributed computing needs of the experiment. However, the core design of PanDA is not experiment specific. The PanDA workload management system is capable of meeting the needs of other data intensive scientific applications. Alpha-Magnetic Spectrometer [4], an astro-particle experiment on the International Space Station, and the Compact Muon Solenoid [5], an LHC experiment, have successfully evaluated PanDA and are pursuing its adoption. In this paper, a description of the new program of work to develop a generic version of PanDA will be given, as well as the progress in extending PanDA's capabilities to support supercomputers and clouds and to leverage intelligent networking. PanDA has demonstrated at a very large scale the value of automated dynamic brokering of diverse workloads across distributed computing resources. The next generation of PanDA will allow other data-intensive sciences and a wider exascale community employing a variety of computing platforms to benefit from ATLAS' experience and proven tools.

Retention behavior of isomeric polycyclic aromatic sulfur heterocycles in gas chromatography on stationary phases of different selectivity

PubMed Central

Wilson, Walter B.; Sander, Lane C.; Oña-Ruales, Jorge O.; Mössner, Stephanie G.; Sidisky, Leonard M.; Lee, Milton L.; Wise, Stephen A.

2017-01-01

Retention indices for 48 polycyclic aromatic sulfur heterocycles (PASHs) were determined using gas chromatography with three different stationary phases: a 50% phenyl phase, a 50% liquid crystalline dimethylpolysiloxane (LC-DMPS) phase, and an ionic liquid (IL) phase. Correlations between the retention behavior on the three stationary phases and PASH geometry (L/B and T, i.e., length-to-breadth ratio and thickness, respectively) were investigated for the following four isomer sets: (1) 4 three-ring molecular mass (MM) 184 Da PASHs, (2) 13 four-ring MM 234 Da PASHs, (3) 10 five-ring MM 258 Da PASHs, and (4) 20 five-ring MM 284 Da PASHs. Correlation coefficients for retention on the 50% LC-DMPS vs L/B ranged from r = 0.50 (MM 284 Da) to r = 0.77 (MM 234 Da). Correlation coefficients for retention on the IL phase vs L/B ranged from r = 0.31 (MM 234 Da) to r = 0.54 (MM 284 Da). Correlation coefficients for retention on the 50% phenyl vs L/B ranged from r = 0.14 (MM 258 Da) to r = 0.59 (MM 284 Da). Several correlation trends are discussed in detail for the retention behavior of PASH on the three stationary phases. PMID:28089272

Retention behavior of isomeric polycyclic aromatic sulfur heterocycles in gas chromatography on stationary phases of different selectivity.

PubMed

Wilson, Walter B; Sander, Lane C; Oña-Ruales, Jorge O; Mössner, Stephanie G; Sidisky, Leonard M; Lee, Milton L; Wise, Stephen A

2017-02-17

Retention indices for 48 polycyclic aromatic sulfur heterocycles (PASHs) were determined using gas chromatography with three different stationary phases: a 50% phenyl phase, a 50% liquid crystalline dimethylpolysiloxane (LC-DMPS) phase, and an ionic liquid (IL) phase. Correlations between the retention behavior on the three stationary phases and PASH geometry (L/B and T, i.e., length-to-breadth ratio and thickness, respectively) were investigated for the following four isomer sets: (1) 4 three-ring molecular mass (MM) 184Da PASHs, (2) 13 four-ring MM 234Da PASHs, (3) 10 five-ring MM 258Da PASHs, and (4) 20 five-ring MM 284Da PASHs. Correlation coefficients for retention on the 50% LC-DMPS vs L/B ranged from r=0.50 (MM 284Da) to r=0.77 (MM 234Da). Correlation coefficients for retention on the IL phase vs L/B ranged from r=0.31 (MM 234Da) to r=0.54 (MM 284Da). Correlation coefficients for retention on the 50% phenyl vs L/B ranged from r=0.14 (MM 258Da) to r=0.59 (MM 284Da). Several correlation trends are discussed in detail for the retention behavior of PASH on the three stationary phases. Published by Elsevier B.V.

Dynamic Assessment for 3- and 4-Year-Old Children Who Use Augmentative and Alternative Communication: Evaluating Expressive Syntax

PubMed Central

Kent-Walsh, Jennifer; King, Marika

2017-01-01

Purpose The developmental readiness to produce early sentences with an iPad communication application was assessed with ten 3- and 4-year-old children with severe speech disorders using graduated prompting dynamic assessment (DA) techniques. The participants' changes in performance within the DA sessions were evaluated, and DA performance was compared with performance during a subsequent intervention. Method Descriptive statistics were used to examine patterns of performance at various cueing levels and mean levels of cueing support. The Wilcoxon signed-ranks test was used to measure changes within the DA sessions. Correlational data were calculated to determine how well performance in DA predicted performance during a subsequent intervention. Results Participants produced targets successfully in DA at various cueing levels, with some targets requiring less cueing than others. Performance improved significantly within the DA sessions—that is, the level of cueing required for accurate productions of the targets decreased during DA sessions. Last, moderate correlations existed between DA scores and performance during the intervention for 3 out of 4 targets, with statistically significant findings for 2 of 4 targets. Conclusion DA offers promise for examining the developmental readiness of young children who use augmentative and alternative communication to produce early expressive language structures. PMID:28614580

Age moderates the effect of acute dopamine depletion on passive avoidance learning.

PubMed

Kelm, Mary Katherine; Boettiger, Charlotte Ann

2015-04-01

Despite extensive links between reinforcement-based learning and dopamine (DA), studies to date have not found consistent effects of acute DA reduction on reinforcement learning in both men and women. Here, we tested the effects of reducing DA on reward- and punishment-based learning using the deterministic passive avoidance learning (PAL) task. We tested 16 (5 female) adults (ages 22-40) in a randomized, cross-over design to determine whether reducing global DA by administering an amino acid beverage deficient in the DA precursors, phenylalanine and tyrosine (P/T[-]), would affect PAL task performance. We found that P/T[-] beverage effects on PAL performance were modulated by age. Specifically, we found that P/T depletion significantly improved learning from punishment with increasing participant age. Participants committed 1.49 fewer passive avoidance errors per additional year of age (95% CI, -0.71 - -2.27, r=-0.74, p=0.001). Moreover, P/T depletion improved learning from punishment in adults (ages 26-40) while it impaired learning from punishment in emerging adults (ages 22-25). We observed similar, but non-significant trends in learning from reward. While there was no overall effect of P/T-depletion on reaction time (RT), there was a relationship between the effect of P/T depletion on PAL performance and RT; those who responded more slowly on the P/T[-] beverage also made more errors on the P/T[-] beverage. When P/T-depletion slowed RT after a correct response, there was a worsening of PAL task performance; there was no similar relationship for the RT after an incorrect response and PAL task performance. Moreover, among emerging adults, changes in mood on the P/T[-] beverage negatively correlated with learning from reward on the P/T[-] beverage. Together, we found that both reward- and punishment-based learning are sensitive to central catecholamine levels, and that these effects of acute DA reduction vary with age. Copyright © 2015 Elsevier Inc. All rights reserved.

Complete genomic sequence of a Tobacco rattle virus isolate from Michigan-grown potatoes.

PubMed

Crosslin, James M; Hamm, Philip B; Kirk, William W; Hammond, Rosemarie W

2010-04-01

Tobacco rattle virus (TRV) causes stem mottle on potato leaves and necrotic arcs and rings in potato tubers, known as corky ringspot disease. Recently, TRV was reported in Michigan potato tubers cv. FL1879 exhibiting corky ringspot disease. Sequence analysis of the RNA-1-encoded 16-kDa gene of the Michigan isolate, designated MI-1, revealed homology to TRV isolates from Florida and Washington. Here, we report the complete genomic sequence of RNA-1 (6,791 nt) and RNA-2 (3,685 nt) of TRV MI-1. RNA-1 is predicted to contain four open reading frames, and the genome structure and phylogenetic analyses of the RNA-1 nucleotide sequence revealed significant homologies to the known sequences of other TRV-1 isolates. The relationships based on the full-length nucleotide sequence were different from than those based on the 16-kDa gene encoded on genomic RNA-1 and reflect sequence variation within a 20-25-aa residue region of the 16-kDa protein. MI-1 RNA-2 is predicted to contain three ORFs, encoding the coat protein (CP), a 37.6-kDa protein (ORF 2b), and a 33.6-kDa protein (ORF 2c). In addition, it contains a region of similarity to the 3' terminus of RNA-1, including a truncated portion of the 16-kDa cistron. Phylogenetic analysis of RNA-2, based on a comparison of nucleotide sequences with other members of the genus Tobravirus, indicates that TRV MI-1 and other North American isolates cluster as a distinct group. TRV M1-1 is only the second North American isolate for which there is a complete sequence of the genome, and it is distinct from the North American isolate TRV ORY. The relationship of the TRV MI-1 isolate to other tobravirus isolates is discussed.

Recruitments of trained citizen volunteering for conventional cardiopulmonary resuscitation are necessary to improve the outcome after out-of-hospital cardiac arrests in remote time-distance area: A nationwide population-based study.

PubMed

Takei, Yutaka; Kamikura, Takahisa; Nishi, Taiki; Maeda, Tetsuo; Sakagami, Satoru; Kubo, Minoru; Inaba, Hideo

2016-08-01

To compare the factors associated with survival after out-of-hospital cardiac arrests (OHCAs) among three time-distance areas (defined as interquartile range of time for emergency medical services response to patient's side). From a nationwide, prospectively collected data on 716,608 OHCAs between 2007 and 2012, this study analyzed 193,914 bystander-witnessed OHCAs without pre-hospital physician involvement. Overall neurologically favourable 1-month survival rates were 7.4%, 4.1% and 1.7% for close, intermediate and remote areas, respectively. We classified BCPR by type (compression-only vs. conventional) and by dispatcher-assisted CPR (DA-CPR) (with vs. without); the effects on time-distance area survival were analyzed by BCPR classification. Association of each BCPR classification with survival was affected by time-distance area and arrest aetiology (p<0.05). The survival rates in the remote area were much higher with conventional BCPR than with compression-only BCPR (odds ratio; 95% confidence interval, 1.26; 1.05-1.51) and with BCPR without DA-CPR than with BCPR with DA-CPR (1.54; 1.29-1.82). Accordingly, we classified BCPR into five groups (no BCPR, compression-only with DA-CPR, conventional with DA-CPR, compression-only without DA-CPR, and conventional without DA-CPR) and analyzed for associations with survival, both cardiac and non-cardiac related, in each time-distance area by multivariate logistic regression analysis. In the remote area, conventional BCPR without DA-CPR significantly improved survival after OHCAs of cardiac aetiology, compared with all the other BCPR groups. Other correctable factors associated with survival were short collapse-to-call and call-to-first CPR intervals. Every effort to recruit trained citizens initiating conventional BCPR should be made in remote time-distance areas. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Plasma proteins of rainbow trout (Oncorhynchus mykiss) isolated by binding to lipopolysaccharide from Aeromonas salmonicida.

PubMed

Hoover, G J; el-Mowafi, A; Simko, E; Kocal, T E; Ferguson, H W; Hayes, M A

1998-07-01

In an attempt to find plasma proteins that might be involved in the constitutive resistance of rainbow trout to furunculosis, a disease caused by Aeromonas salmonicida (AS), we purified serum and plasma proteins based on their calcium- and carbohydrate-dependent affinity for A. salmonicida lipopolysaccharide (LPS) coupled to an epoxy-activated synthetic matrix (Toyopearl AF Epoxy 650M). A multimeric family of high molecular weight (96 to 200-kDa) LPS-binding proteins exhibiting both calcium and mannose dependent binding was isolated. Upon reduction the multimers collapsed to subunits of approximately 16-kDa as estimated by 1D-PAGE and exhibited pI values of 5.30 and 5.75 as estimated from 2D-PAGE. Their N-terminal sequences were related to rainbow trout ladderlectin (RT-LL), a Sepharose-binding protein. Polyclonal antibodies to the LPS-purified 16-kDa subunits recognized both the reduced 16-kDa subunits and the non-reduced multimeric forms. A calcium- and N-acetylglucosamine (GlcNAc)-dependent LPS-binding multimeric protein (approximately 207-kDa) composed of 34.5-kDa subunits was purified and found to be identical to trout serum amyloid P (SAP) by N-terminal sequence (DLQDLSGKVFV). A protein of 24-kDa, in reduced and non-reduced conditions, was isolated and had N-terminal sequence identity with a known C-reactive protein (CRP) homologue, C-polysaccharide-binding protein 2 (TCBP2) of rainbow trout. A novel calcium-dependent LPS-binding protein was purified and termed rainbow trout lectin 37 (RT-L37). This protein, composed of dimers, tetramers and pentamers of 37 kDa subunits (pI 5.50-6.10) with N-terminal sequence (IQE(D/N)GHAEAPGATTVLNEILR) showed no close homology to proteins known or predicted from cDNA sequences. These findings demonstrate that rainbow trout have several blood proteins with lectin properties for the LPS of A. salmonicida; the biological functions of these proteins in resistance to furunculosis are still unknown.

Tunneling Kinetics and Nonadiabatic Proton-Coupled Electron Transfer in Proteins: The Effect of Electric Fields and Anharmonic Donor-Acceptor Interactions.

PubMed

Salna, Bridget; Benabbas, Abdelkrim; Russo, Douglas; Champion, Paul M

2017-07-20

A proper description of proton donor-acceptor (D-A) distance fluctuations is crucial for understanding tunneling in proton-coupled electron transport (PCET). The typical harmonic approximation for the D-A potential results in a Gaussian probability distribution, which does not appropriately reflect the electronic repulsion forces that increase the energetic cost of sampling shorter D-A distances. Because these shorter distances are the primary channel for thermally activated tunneling, the analysis of tunneling kinetics depends sensitively on the inherently anharmonic nature of the D-A interaction. Thus, we have used quantum chemical calculations to account for the D-A interaction and developed an improved model for the analysis of experimental tunneling kinetics. Strong internal electric fields are also considered and found to contribute significantly to the compressive forces when the D-A distance distribution is positioned below the van der Waals contact distance. This model is applied to recent experiments on the wild type (WT) and a double mutant (DM) of soybean lipoxygenase-1 (SLO). The compressive force necessary to prepare the tunneling-active distribution in WT SLO is found to fall in the ∼ nN range, which greatly exceeds the measured values of molecular motor and protein unfolding forces. This indicates that ∼60-100 MV/cm electric fields, aligned along the D-A bond axis, must be generated by an enzyme conformational interconversion that facilitates the PCET tunneling reaction. Based on the absolute value of the measured tunneling rate, and using previously calculated values of the electronic matrix element, the population of this tunneling-active conformation is found to lie in the range 10 -5 -10 -7 , indicating this is a rare structural fluctuation that falls well below the detection threshold of recent ENDOR experiments. Additional analysis of the DM tunneling kinetics leads to a proposal that a disordered (high entropy) conformation could be tunneling-active due to its broad range of sampled D-A distances.

Sequence and expression variations suggest an adaptive role for the DA1-like gene family in the evolution of soybeans.

PubMed

Zhao, Man; Gu, Yongzhe; He, Lingli; Chen, Qingshan; He, Chaoying

2015-05-15

The DA1 gene family is plant-specific and Arabidopsis DA1 regulates seed and organ size, but the functions in soybeans are unknown. The cultivated soybean (Glycine max) is believed to be domesticated from the annual wild soybeans (Glycine soja). To evaluate whether DA1-like genes were involved in the evolution of soybeans, we compared variation at both sequence and expression levels of DA1-like genes from G. max (GmaDA1) and G. soja (GsoDA1). Sequence identities were extremely high between the orthologous pairs between soybeans, while the paralogous copies in a soybean species showed a relatively high divergence. Moreover, the expression variation of DA1-like paralogous genes in soybean was much greater than the orthologous gene pairs between the wild and cultivated soybeans during development and challenging abiotic stresses such as salinity. We further found that overexpressing GsoDA1 genes did not affect seed size. Nevertheless, overexpressing them reduced transgenic Arabidopsis seed germination sensitivity to salt stress. Moreover, most of these genes could improve salt tolerance of the transgenic Arabidopsis plants, corroborated by a detection of expression variation of several key genes in the salt-tolerance pathways. Our work suggested that expression diversification of DA1-like genes is functionally associated with adaptive radiation of soybeans, reinforcing that the plant-specific DA1 gene family might have contributed to the successful adaption to complex environments and radiation of the plants.

Fibroblast growth factor receptor signaling affects development and function of dopamine neurons - inhibition results in a schizophrenia-like syndrome in transgenic mice.

PubMed

Klejbor, Ilona; Myers, Jason M; Hausknecht, Kathy; Corso, Thomas D; Gambino, Angelo S; Morys, Janusz; Maher, Pamela A; Hard, Robert; Richards, Jerry; Stachowiak, Ewa K; Stachowiak, Michal K

2006-06-01

Developing and mature midbrain dopamine (DA) neurons express fibroblast growth factor (FGF) receptor-1 (FGFR1). To determine the role of FGFR1 signaling in the development of DA neurons, we generated transgenic mice expressing a dominant negative mutant [FGFR1(TK-)] from the catecholaminergic, neuron-specific tyrosine hydroxylase (TH) gene promoter. In homozygous th(tk-)/th(tk-) mice, significant reductions in the size of TH-immunoreactive neurons were found in the substantia nigra compacta (SNc) and the ventral tegmental area (VTA) at postnatal days 0 and 360. Newborn th(tk-)/th(tk-) mice had a reduced density of DA neurons in both SNc and VTA, and the changes in SNc were maintained into adulthood. The reduced density of DA transporter in the striatum further demonstrated an impaired development of the nigro-striatal DA system. Paradoxically, the th(tk-)/th(tk-) mice had increased levels of DA, homovanilic acid and 3-methoxytyramine in the striatum, indicative of excessive DA transmission. These structural and biochemical changes in DA neurons are similar to those reported in human patients with schizophrenia and, furthermore, these th(tk-)/th(tk-) mice displayed an impaired prepulse inhibition that was reversed by a DA receptor antagonist. Thus, this study establishes a new developmental model for a schizophrenia-like disorder in which the inhibition of FGF signaling leads to alterations in DA neurons and DA-mediated behavior.

Effect of DA-8031, a novel oral compound for premature ejaculation, on male rat sexual behavior.

PubMed

Kang, Kyung Koo; Sung, Ji Hyun; Kim, Soon Hoe; Lee, Sukhyang

2014-03-01

DA-8031 is a potent and selective serotonin transporter inhibitor developed for the treatment of premature ejaculation. The aim of the present study was to investigate the effects of DA-8031 on male sexual behavior in a rat model. Sexual behavior was examined after an acute oral administration of 10, 30 or 100 mg/kg of DA-8031 in copulation studies with female rats. Pharmacokinetic parameters were calculated after oral administration of DA-8031 at a dose level of 30 mg/kg. DA-8031 treatment produced a dose-dependent increase in ejaculation latency time and showed statistical significance at 30 and 100 mg/kg dosage levels compared with the vehicle (P < 0.05). In addition, DA-8031 treatment reduced the mean number of ejaculations in a dose-dependent manner. No changes in post-ejaculatory interval, numbers of mounts, intromissions or ejaculations were observed at any dose. In pharmacokinetic study, the blood concentration of DA-8031 peaked at 0.38 ± 0.14 h after oral administration, and then rapidly declined with a half-life of 1.79 ± 0.32 h. Treatment with DA-8031 delays the ejaculation latency time without affecting the initiation of mounting behavior or post-ejaculatory interval in rats. Furthermore, DA-8031 is rapidly absorbed and eliminated after oral administration in rats. These preclinical findings provide a clue for the clinical testing of DA-8031 as an "on-demand" agent for premature ejaculation. © 2013 The Japanese Urological Association.

78 FR 46930 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... Counseling and Information Sheet; DA Form 5434; OMB Control Number 0702-TBD. Needs And Uses: The information.... Frequency: On Occasion. SUPPLEMENTARY INFORMATION: Summary of Information Collection Respondents are DA Civilian employees and Soldiers. Departing Soldiers or DA Civilian employees complete the DA Form 5434...

A Comparison of Forecast Error Generators for Modeling Wind and Load Uncertainty

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

Lu, Ning; Diao, Ruisheng; Hafen, Ryan P.

2013-12-18

This paper presents four algorithms to generate random forecast error time series, including a truncated-normal distribution model, a state-space based Markov model, a seasonal autoregressive moving average (ARMA) model, and a stochastic-optimization based model. The error time series are used to create real-time (RT), hour-ahead (HA), and day-ahead (DA) wind and load forecast time series that statistically match historically observed forecasting data sets, used for variable generation integration studies. A comparison is made using historical DA load forecast and actual load values to generate new sets of DA forecasts with similar stoical forecast error characteristics. This paper discusses and comparesmore » the capabilities of each algorithm to preserve the characteristics of the historical forecast data sets.« less

Extraction of Features from High-resolution 3D LiDaR Point-cloud Data

NASA Astrophysics Data System (ADS)

Keller, P.; Kreylos, O.; Hamann, B.; Kellogg, L. H.; Cowgill, E. S.; Yikilmaz, M. B.; Hering-Bertram, M.; Hagen, H.

2008-12-01

Airborne and tripod-based LiDaR scans are capable of producing new insight into geologic features by providing high-quality 3D measurements of the landscape. High-resolution LiDaR is a promising method for studying slip on faults, erosion, and other landscape-altering processes. LiDaR scans can produce up to several billion individual point returns associated with the reflection of a laser from natural and engineered surfaces; these point clouds are typically used to derive a high-resolution digital elevation model (DEM). Currently, there exist only few methods that can support the analysis of the data at full resolution and in the natural 3D perspective in which it was collected by working directly with the points. We are developing new algorithms for extracting features from LiDaR scans, and present method for determining the local curvature of a LiDaR data set, working directly with the individual point returns of a scan. Computing the curvature enables us to rapidly and automatically identify key features such as ridge-lines, stream beds, and edges of terraces. We fit polynomial surface patches via a moving least squares (MLS) approach to local point neighborhoods, determining curvature values for each point. The size of the local point neighborhood is defined by a user. Since both terrestrial and airborne LiDaR scans suffer from high noise, we apply additional pre- and post-processing smoothing steps to eliminate unwanted features. LiDaR data also captures objects like buildings and trees complicating greatly the task of extracting reliable curvature values. Hence, we use a stochastic approach to determine whether a point can be reliably used to estimate curvature or not. Additionally, we have developed a graph-based approach to establish connectivities among points that correspond to regions of high curvature. The result is an explicit description of ridge-lines, for example. We have applied our method to the raw point cloud data collected as part of the GeoEarthScope B-4 project on a section of the San Andreas Fault (Segment SA09). This section provides an excellent test site for our method as it exposes the fault clearly, contains few extraneous structures, and exhibits multiple dry stream-beds that have been off-set by motion on the fault.

Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

PubMed

Anselmi, L; Toti, L; Bove, C; Travagli, R A

2017-11-01

Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1 ) assess the gastric effects of brain stem DA application, 2 ) identify the DA receptor subtype, and, 3 ) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

Reciprocal responsiveness of nucleus accumbens shell and core dopamine to food- and drug-conditioned stimuli.

PubMed

Bassareo, Valentina; Musio, Paolo; Di Chiara, Gaetano

2011-04-01

Drugs of abuse and palatable food share the ability to stimulate dopamine (DA) transmission in the nucleus accumbens shell. However, while the stimulation of shell DA by food undergoes habituation, that by drugs of abuse does not. This study aims to directly compare the changes of extracellular DA, by microdialysis, in shell and core and prefrontal cortex (PFCX) in response to food- and drug-conditioned stimuli (CSs). Rats were trace-conditioned by Fonzies box (FB) or vanilla box (VB; CS), followed by food: Fonzies, intraoral chocolate solution (food-unconditioned stimulus (US)) and morphine (1.0 mg/Kg sc; drug US). Control (unconditioned) rats received standard food instead of Fonzies, tap water instead of chocolate, saline instead of morphine. Food-CSs increased core but not shell DA, while drug-CSs did the opposite. Food and drug-CSs both increased PFCX DA. Exposure to food-CSs potentiated core and PFCX DA response to food while shell responsiveness was dependent upon the relative CS and US nature. If the CS was intrinsic to the food US (CS = FB/US = Fonzies) the response of shell DA to the US was abolished. If the CS was extrinsic to the food US (CS = FB/US = chocolate; CS = VB/US = Fonzies), shell DA increased in response to the US. Exposure to the drug-CS potentiated the DA response to the drug-US in the shell and in the PFCX, but not in the core. Drug-CSs differentially activate DA as compared to food-CSs in shell and core and differentially affect DA response to the US in these areas. These differences might be relevant for the role of DA in the mechanism of drug addiction.

Two-step processing for activation of the cytolysin/hemolysin of Vibrio cholerae O1 biotype El Tor: nucleotide sequence of the structural gene (hlyA) and characterization of the processed products.

PubMed

Yamamoto, K; Ichinose, Y; Shinagawa, H; Makino, K; Nakata, A; Iwanaga, M; Honda, T; Miwatani, T

1990-12-01

Vibrio cholerae O1 biotype El Tor produces and secretes a 65-kDa cytolysin/hemolysin into the culture medium. We cloned the structural gene (hlyA) for the cytolysin from the total DNA of a V. cholerae O1 El Tor strain, N86. Nucleotide sequence analysis of hlyA revealed an open reading frame consisting of 2,223 bp which can code for a protein of 741 amino acids with a molecular weight of 81,961. Consistent with this, a 79-kDa protein was identified as the product of hlyA by maxicell analysis in Escherichia coli. N-terminal amino acids of this 79-kDa HlyA protein and those of a 65-kDa El Tor cytolysin purified from V. cholerae were Asn-26 and Asn-158, respectively. The 82- and 79-kDa precursors of the 65-kDa mature cytolysin were found in V. cholerae by pulse-chase labeling and Western blot (immunoblot) analysis of hlyA products. Hemolytic activity of the 79-kDa HlyA protein from E. coli was less than 5% that for the 65-kDa cytolysin from V. cholerae. Our results suggest that in V. cholerae, the 82-kDa preprotoxin synthesized in the cytoplasm is secreted through the membranes into the culture medium as the 79-kDa inactive protoxin after cleavage of the signal peptide and is then further processed into the 65-kDa active cytolysin by release of the N-terminal 15-kDa fragment.

Concentration-dependent activation of dopamine receptors differentially modulates GABA release onto orexin neurons.

PubMed

Linehan, Victoria; Trask, Robert B; Briggs, Chantalle; Rowe, Todd M; Hirasawa, Michiru

2015-08-01

Dopamine (DA) and orexin neurons play important roles in reward and food intake. There are anatomical and functional connections between these two cell groups: orexin peptides stimulate DA neurons in the ventral tegmental area and DA inhibits orexin neurons in the hypothalamus. However, the cellular mechanisms underlying the action of DA on orexin neurons remain incompletely understood. Therefore, the effect of DA on inhibitory transmission to orexin neurons was investigated in rat brain slices using the whole-cell patch-clamp technique. We found that DA modulated the frequency of spontaneous and miniature IPSCs (mIPSCs) in a concentration-dependent bidirectional manner. Low (1 μM) and high (100 μM) concentrations of DA decreased and increased IPSC frequency, respectively. These effects did not accompany a change in mIPSC amplitude and persisted in the presence of G-protein signaling inhibitor GDPβS in the pipette, suggesting that DA acts presynaptically. The decrease in mIPSC frequency was mediated by D2 receptors whereas the increase required co-activation of D1 and D2 receptors and subsequent activation of phospholipase C. In summary, our results suggest that DA has complex effects on GABAergic transmission to orexin neurons, involving cooperation of multiple receptor subtypes. The direction of dopaminergic influence on orexin neurons is dependent on the level of DA in the hypothalamus. At low levels DA disinhibits orexin neurons whereas at high levels it facilitates GABA release, which may act as negative feedback to curb the excitatory orexinergic output to DA neurons. These mechanisms may have implications for consummatory and motivated behaviours. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Increased dopamine transporter function as a mechanism for dopamine hypoactivity in the adult infralimbic medial prefrontal cortex following adolescent social stress.

PubMed

Novick, Andrew M; Forster, Gina L; Hassell, James E; Davies, Daniel R; Scholl, Jamie L; Renner, Kenneth J; Watt, Michael J

2015-10-01

Being bullied during adolescence is associated with later mental illnesses characterized by deficits in cognitive tasks mediated by prefrontal cortex (PFC) dopamine (DA). Social defeat of adolescent male rats, as a model of teenage bullying victimization, results in medial PFC (mPFC) dopamine (DA) hypofunction in adulthood that is associated with increased drug seeking and working memory deficits. Increased expression of the DA transporter (DAT) is also seen in the adult infralimbic mPFC following adolescent defeat. We propose the functional consequence of this increased DAT expression is enhanced DA clearance and subsequently decreased infralimbic mPFC DA availability. To test this, in vivo chronoamperometry was used to measure changes in accumulation of the DA signal following DAT blockade, with increased DAT-mediated clearance being reflected by lower DA signal accumulation. Previously defeated rats and controls were pre-treated with the norepinephrine transporter (NET) inhibitor desipramine (20 mg/kg, ip.) to isolate infralimbic mPFC DA clearance to DAT, then administered the selective DAT inhibitor GBR-12909 (20 or 40 mg/kg, sc.). Sole NET inhibition with desipramine produced no differences in DA signal accumulation between defeated rats and controls. However, rats exposed to adolescent social defeat demonstrated decreased DA signal accumulation compared to controls in response to both doses of GBR-12909, indicating greater DAT-mediated clearance of infralimbic mPFC DA. These results suggest that protracted increases in infralimbic mPFC DAT function represent a mechanism by which adolescent social defeat stress produces deficits in adult mPFC DA activity and corresponding behavioral and cognitive dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chronic lithium treatment rectifies maladaptive dopamine release in the nucleus accumbens.

PubMed

Can, Adem; Frost, Douglas O; Cachope, Roger; Cheer, Joseph F; Gould, Todd D

2016-11-01

Chronic lithium treatment effectively reduces behavioral phenotypes of mania in humans and rodents. The mechanisms by which lithium exerts these actions are poorly understood. Pre-clinical and clinical evidence have implicated increased mesolimbic dopamine (DA) neurotransmission with mania. We used fast-scan cyclic voltammetry to characterize changes in extracellular DA concentrations in the nucleus accumbens (NAc) core evoked by 20 and 60 Hz electrical stimulation of the ventral tegmental area (VTA) in C57BL6/J mice treated either acutely or chronically with lithium. The effects of chronic lithium treatment on the availability of DA for release were assessed by depleting readily releasable DA using short inter-train intervals, or administering d-amphetamine acutely to mobilize readily releasable DA. Chronic, but not acute, lithium treatment decreased the amplitude of DA responses in the NAc following 60 Hz pulse train stimulation. Neither lithium treatment altered the kinetics of DA release or reuptake. Chronic treatment did not impact the progressive reduction in the amplitude of DA responses when, using 20 or 60 Hz pulse trains, the VTA was stimulated every 6 s to deplete DA. Specifically, the amplitude of DA responses to 60 Hz pulse trains was initially reduced compared to control mice, but by the fifth pulse train, there was no longer a treatment effect. However, chronic lithium treatment attenuated d-amphetamine-induced increases in DA responses to 20 Hz pulse trains stimulation. Our data suggest that long-term administration of lithium may ameliorate mania phenotypes by normalizing the readily releasable DA pool in VTA axon terminals in the NAc. Read the Editorial Highlight for this article on Page 520. © 2016 International Society for Neurochemistry.

Insulin stimulates the tyrosine phosphorylation of a 61-kilodalton protein in rat adipocytes.

PubMed

Mooney, R A; Bordwell, K L

1992-03-01

Insulin stimulated the tyrosine phosphorylation of a 61-kilodalton (kDa) protein in rat adipocytes prelabeled for 2 h with [32P]orthophosphate. Tyrosine phosphorylation of this 61-kDa protein displayed very similar insulin concentration dependency to receptor autophosphorylation and tyrosine phosphorylation of a high molecular mass receptor substrate of 160 kDa. Phosphorylation of the 61-kDa protein was very rapid with maximum labeling attained at 30 sec, paralleling that of the other two proteins. Phosphoamino acid analysis revealed that each of the insulin-responsive phosphoproteins contained phosphoserine as well as phosphotyrosine, though the ratio of two phosphoamino acids recovered from each protein differed. The 61-kDa protein yielded relatively equal proportions of phosphoserine and phosphotyrosine. In contrast, the insulin receptor yielded relatively more label on phosphotyrosine than phosphoserine, whereas label incorporated into the 160-kDa protein was recovered primarily on phosphoserine. Cleveland peptide maps using either Staphylococcus aureus V8 proteinase or chymotrypsin revealed no similarities between the 61-kDa protein and the other tyrosine phosphorylated proteins. With subcellular fractionation, the 160-kDa protein was found in equal proportions in the high speed pellet (100,000 g) and supernatant. The 61-kDa protein had a similar distribution to that of the 160-kDa protein but was also detected in the low speed pellet (10,000 g). The insulin receptor was localized to the low speed pellet. In summary, rat adipocytes contain an insulin-dependent phosphotyrosyl protein of 61 kDa which is distinct from the more prominent high molecular mass receptor substrate. This 61-kDa protein has characteristics consistent with it being a substrate for the insulin receptor tyrosine kinase.

Depletion of nucleus accumbens dopamine leads to impaired reward and aversion processing in mice: Relevance to motivation pathologies.

PubMed

Bergamini, Giorgio; Sigrist, Hannes; Ferger, Boris; Singewald, Nicolas; Seifritz, Erich; Pryce, Christopher R

2016-10-01

Dopamine (DA) neurotransmission, particularly the ventral tegmental area-nucleus accumbens (VTA-NAcc) projection, underlies reward and aversion processing, and deficient DA function could underlie motivational impairments in psychiatric disorders. 6-hydroxydopamine (6-OHDA) injection is an established method for chronic DA depletion, principally applied in rat to study NAcc DA regulation of reward motivation. Given the increasing focus on studying environmental and genetic regulation of DA function in mouse models, it is important to establish the effects of 6-OHDA DA depletion in mice, in terms of reward and aversion processing. This mouse study investigated effects of 6-OHDA-induced NAcc DA depletion using the operant behavioural test battery of progressive ratio schedule (PRS), learned non-reward (LNR), learned helplessness (LH), treadmill, and in addition Pavlovian fear conditioning. 6-OHDA NAcc DA depletion, confirmed by ex vivo HPLC-ED, reduced operant responding: for gustatory reward under effortful conditions in the PRS test; to a stimulus recently associated with gustatory non-reward in the LNR test; to escape footshock recently experienced as uncontrollable in the LH test; and to avoid footshock by physical effort in the treadmill test. Evidence for specificity of effects to NAcc DA was provided by lack of effect of medial prefrontal cortex DA depletion in the LNR and LH tests. These findings add significantly to the evidence that NAcc DA is a major regulator of behavioural responding, particularly at the motivational level, to both reward and aversion. They demonstrate the suitability of mouse models for translational study of causation and reversal of pathophysiological DA function underlying motivation psychopathologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Independent mediation of unconditioned motor behavior by striatal D1 and D2 receptors in rats depleted of dopamine as neonates.

PubMed

Bruno, J P; Byrnes, E M; Johnson, B J

1995-11-01

The effects of systemic administration of DA receptor antagonists suggest that unconditioned motor behavior in rats depleted of DA as neonates continues to be dependent upon dopaminergic transmission, yet the specific contribution of D1 and D2 receptors to these behaviors has been altered. The purpose of the present study was to determine whether these depletion-induced receptor changes are occurring at the level of striatal DA terminals and their targets. The ability of bilateral intrastriatal injections (0.5 microliter) of DA receptor antagonists to induce motoric deficits was determined in adult rats treated with vehicle or 6-OHDA (100 micrograms, intraventricular) on postnatal day 3. Administration of the D1-like antagonist SCH 23390 (0.5-2.0 micrograms) or the D2-like antagonist clebopride (1.0-4.0 micrograms) induced dose-dependent akinesia, catalepsy, and somatosensory neglect in vehicle-treated controls. In contrast, neither antagonist produced deficits in rats depleted of forebrain DA as neonates. However, combined administration of SCH 23390 + clebopride induced similar akinesia, catalepsy, and somatosensory neglect in both controls and DA depleted animals. Animals depleted of DA were more sensitive than controls to the low doses of this combined D1 + D2 antagonism. These results demonstrate that activation of striatal DA receptors remains necessary for unconditioned motor behavior in rats depleted of DA as neonates. However, the specific contributions of D1- and D2-like receptors to these behaviors differ between intact animals and those depleted of DA as neonates. The ability of endogenous DA acting at either D1 or D2 receptors to support spontaneous motor behavior in rats depleted of DA as neonates may contribute to their relative sparing from parkinsonian deficits.

Effect of 14-kDa and 47-kDa protein molecules of age garlic extract on peritoneal macrophages.

PubMed

Daneshmandi, Saeed; Hajimoradi, Monire; Ahmadabad, Hasan Namdar; Hassan, Zuhair Mohammad; Roudbary, Maryam; Ghazanfari, Tooba

2011-03-01

Garlic (Allium sativum), traditionally being used as a spice worldwide, has different applications and is claimed to possess beneficial effects in several health ailments such as tumor and atherosclerosis. Garlic is also an immunomodulator and its different components are responsible for different properties. The present work aimed to assess the effect of protein fractions of garlic on peritoneal macrophages. 14-kDa and 47-kDa protein fractions of garlic were purified. Mice peritoneal macrophages were lavaged and cultured in a microtiter plate and exposed to different concentrations of garlic proteins. MTT assay was performed to evaluate the viability of macrophage. The amount of nitric oxide (NO) was detected in culture supernatants of macrophages by Griess reagent and furthermore, the cytotoxicity study of culture supernatants was carried out on WEHI-164 fibrosarcoma cell line as tumor necrosis factor-α bioassay. MTT assay results for both 14-kDa and 47-kDa protein fractions of stimulated macrophages were not significant (P > 0.05). Both 14-kDa and 47-kDa fractions significantly suppressed production of NO from macrophages (P = 0.007 and P = 0.003, respectively). Cytotoxicity of macrophages' supernatant on WEHI-164 fibrosarcoma cells was not affected by garlic protein fractions (P = 0.066 for 14-kDa and P = 0.085 for 47-kDa fractions). according to our finding, 14-kDa and 47-kDa fractions of aged garlic extract are able to suppress NO production from macrophages, which can be used as a biological advantage. These molecules had no cytotoxic effect on macrophages and do not increase tumoricidal property of macrophages.

Development and testing of a decision aid for women considering delayed breast reconstruction.

PubMed

Metcalfe, Kelly; Zhong, Toni; O'Neill, Anne C; McCready, David; Chan, Linda; Butler, Kate; Brennenstuhl, Sarah; Hofer, Stefan O P

2018-03-01

The decision to have post-mastectomy breast reconstruction (PMBR) is highly complex and many women feel ill equipped to make this decision. Decision aids have been advocated to promote patient involvement in decision-making by streamlining and standardizing communication between the patient and the health care professional. In this study, we report on the development and testing of a decision aid (DA) for breast cancer survivors considering delayed PMBR. The DA was developed and evaluated in three phases. The first phase included the development of the DA with input and review by practitioners and key stakeholders. The second phase involved pilot testing of the feasibility and acceptability of the DA with a convenience sample of women with delayed PMBR. The third phase involved a pretest/post-test evaluation of the DA for women who were making decisions about their PMBR options. The DA was developed using the Ottawa Decision Support Framework. In the second phase of the study, 21 women completed the acceptability survey, of whom 100% reported that they would recommend the DA to other women. In the third phase, decisional conflict decreased significantly (p < 0.001) and knowledge increased significantly (p < 0.001) from prior to using the DA to 1-2 weeks after using the DA. The DA is feasible and acceptable to women considering delayed PMBR. Furthermore, the DA is effective at reducing decisional conflict and increasing knowledge about delayed PMBR. The DA is an appropriate tool to be used in addition with standard care in women considering PMBR. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Informed decision making before prostate-specific antigen screening: Initial results using the American Cancer Society (ACS) Decision Aid (DA) among medically underserved men.

PubMed

Gökce, Mehmet I; Wang, Xuemei; Frost, Jacqueline; Roberson, Pamela; Volk, Robert J; Brooks, Durado; Canfield, Steven E; Pettaway, Curtis A

2017-02-15

The American Cancer Society (ACS) recommends men have the opportunity to make an informed decision about screening for prostate cancer (PCa). The ACS developed a unique decision aid (ACS-DA) for this purpose. However, to date, studies evaluating the efficacy of the ACS-DA are lacking. The authors evaluated the ACS-DA among a cohort of medically underserved men (MUM). A multiethnic cohort of MUM (n = 285) was prospectively included between June 2010 and December 2014. The ACS-DA was presented in a group format. Levels of knowledge on PCa were evaluated before and after the presentation. Participants' decisional conflict and thoughts about the presentation also were evaluated. Logistic regression analyses were performed to determine factors associated with having an adequate level of knowledge. Before receiving the ACS-DA, 33.1% of participants had adequate knowledge on PCa, and this increased to 77% after the DA (P < .0001). On multivariate analysis, higher education level (odds ratio, 11.19; P = .001) and history of another cancer (odds ratio, 7.45; P = .03) were associated with having adequate knowledge after receiving the DA. Levels of decisional conflict were low and were correlated with levels of knowledge after receiving the DA. The majority of men also rated the presentation as favorable and would recommend the ACS-DA to others. Use of the ACS-DA was feasible among MUM and led to increased PCa knowledge. This also correlated with low levels of decisional conflict. The ACS-DA presented to groups of men may serve as a feasible tool for informed decision making in a MUM population. Cancer 2017;123:583-591. © 2016 American Cancer Society. © 2016 American Cancer Society.

High Doses of Amphetamine Augment, Rather Than Disrupt, Exocytotic Dopamine Release in the Dorsal and Ventral Striatum of the Anesthetized Rat

PubMed Central

Ramsson, Eric S.; Howard, Christopher D.; Covey, Dan P.; Garris, Paul A.

2011-01-01

High doses of amphetamine (AMPH) are thought to disrupt normal patterns of action potential-dependent dopaminergic neurotransmission by depleting vesicular stores of dopamine (DA) and inducing robust non-exocytotic DA release or efflux via dopamine transporter (DAT) reversal. However, these cardinal AMPH actions have been difficult to establish definitively in vivo. Here, we use fast-scan cyclic voltammetry (FSCV) in the urethane-anesthetized rat to evaluate the effects of 10 and 20 mg/kg AMPH on vesicular DA release and DAT function in dorsal and ventral striata. An equivalent high dose of cocaine (40 mg/kg) was also examined for comparison to psychostimulants acting preferentially by DAT inhibition. Parameters describing exocytotic DA release and neuronal DA uptake were determined from dynamic DA signals evoked by mild electrical stimulation previously established to be reinforcing. High-sensitivity FSCV with nanomolar detection was used to monitor changes in the background voltammetric signal as an index of DA efflux. Both doses of AMPH and cocaine markedly elevated evoked DA levels over the entire 2-h time course in the dorsal and ventral striatum. These increases were mediated by augmented vesicular DA release and diminished DA uptake typically acting concurrently. AMPH, but not cocaine, induced a slow, DA-like rise in some baseline recordings. However, this effect was highly variable in amplitude and duration, modest, and generally not present at all. These data thus describe a mechanistically similar activation of action potential-dependent dopaminergic neurotransmission by AMPH and cocaine in vivo. Moreover, DA efflux appears to be a unique, but secondary, AMPH action. PMID:21806614

A comparison of ED and direct admission care of cancer patients with febrile neutropenia.

PubMed

Owolabi, Diwura K; Rowland, Richard; King, Lauren; Miller, Rick; Hegde, Gajanan G; Shang, Jennifer; Lister, John; Venkat, Arvind

2015-07-01

We compared the quality of care in admitted febrile neutropenic cancer patients presenting through the emergency department (ED) vs those directly admitted (DA) from the clinic or infusion center. We hypothesized that the quality of care would be comparable between these 2 pathways. We conducted a retrospective, observational cohort study of all adult cancer patients hospitalized with subjective or objective fever (≥100.4°F) and documented neutropenia (absolute neutrophil count ≤1000/mm(3)) from January 1, 2011 to June 30, 2013, at 2 hospitals. Two investigators retrieved data including patient age, sex, race, tumor type, blood culture growth, temperature (actual or reported), pathway to admission (ED or DA), time to antibiotic administration, length of stay, and the Multinational Association for Supportive Care in Cancer (MASCC) risk score. The primary outcome measures were time to antibiotic administration, appropriateness of antibiotic(s) administered based on published guidelines, length of stay, and MASCC score-based risk assessment. We used the t test for the difference between 2 means with unequal population variances to compare these outcome measures between ED and DA patients. One hundred twenty-seven visits met inclusion criteria (42 [33%] ED visits, 85 [67%] DA visits). Mean time to antibiotic administration, mean length of stay, appropriateness of antibiotics, and MASCC score-based risk assessment were comparable between ED and DA visits (P>.05 for all comparisons). The quality of care for febrile neutropenia in patients presenting through the ED was comparable to those directly admitted to the hospital in this 2-center study. Copyright © 2015 Elsevier Inc. All rights reserved.

Naval Supply Systems Command: Data Administration Planning and Implementation

DTIC Science & Technology

1989-03-01

determined that management’s lack of understanding is an inhibitor of successful DA. Equally important is the DA group’s comprehension of...is the actual staff responsible for DA. Kahn [Ref. 5] found that an insufficient DA staff was another inhibitor of successful DA implementation. Two...Logistic Network ( NLN ) architecture. 7 3. NAVSUP Strategic Directions Three of NAVSUP’s strategic directions pertain to this study. The first is the

Discriminant forest classification method and system

DOEpatents

Chen, Barry Y.; Hanley, William G.; Lemmond, Tracy D.; Hiller, Lawrence J.; Knapp, David A.; Mugge, Marshall J.

2012-11-06

A hybrid machine learning methodology and system for classification that combines classical random forest (RF) methodology with discriminant analysis (DA) techniques to provide enhanced classification capability. A DA technique which uses feature measurements of an object to predict its class membership, such as linear discriminant analysis (LDA) or Andersen-Bahadur linear discriminant technique (AB), is used to split the data at each node in each of its classification trees to train and grow the trees and the forest. When training is finished, a set of n DA-based decision trees of a discriminant forest is produced for use in predicting the classification of new samples of unknown class.

Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

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

Qin, Tian; Wang, Chenlong; Chen, Xuewei

Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing themore » coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in tumor microenvironment.« less

The Protective Effect of Pregnancy on Risk for Drug Abuse: A Population, Co-relative, Co-spouse, and Within-Individual Analysis

PubMed Central

Kendler, Kenneth S.; Ohlsson, Henrik; Svikis, Dace S.; Sundquist, Kristina; Sundquist, Jan

2017-01-01

Objective To determine whether pregnancy is an intrinsic motivator for drug abuse (DA) cessation. Method We conducted, in Swedish females born 1980–1990 who gave birth at ages 20–35 (N=149,512), prospective cohort, co-relative, co-spouse, and within-person analyses of registration for DA during pregnancy. DA was assessed from medical, criminal and pharmacy registries. Results In the population, rates of DA were lower during pregnancy (unadjusted OR=0.67, 95% CIs 0.60–0.74). Compared to population results, the negative association between pregnancy and DA was moderately stronger in cousins (OR=0.49, 0.39–0.62) and substantially stronger in siblings (OR=0.35, 0.24–0.51) discordant for pregnancy. The estimated OR for DA in pregnancy-discordant monozygotic twins was even stronger: 0.17 (0.10–0.31). Within-individuals, the OR for DA while pregnant compared to an equivalent pre-pregnancy interval was similar to that seen in pregnancy-discordant monozygotic twins: 0.22 (0.19–0.26). Compared to cohabiting fathers, mothers had a greater reduction in risk for DA during pregnancy (OR=0.40, 0.34–0.47). Pregnancy was more protective in those with low parental education and without a cohabiting actively drug abusing father. Compared to pre-pregnancy baseline, within-individual analyses indicate risk for DA is also substantially reduced post-partum e.g. day 0–242 OR=0.13 (0.11–0.16). Conclusions Risk for DA in women is substantially reduced during pregnancy. Multiple analyses suggest that this association is largely causal, suggesting that pregnancy is indeed a strong intrinsic motivator for DA cessation. Similar strong protective effects may be present immediately post-partum. Our results have implications for our etiologic models of DA and especially for contingency management programs seeking to reduce DA risk. PMID:28595490

Serotonin System Implication in l-DOPA-Induced Dyskinesia: From Animal Models to Clinical Investigations

PubMed Central

Carta, Manolo; Tronci, Elisabetta

2014-01-01

In the recent years, the serotonin system has emerged as a key player in the induction of l-DOPA-induced dyskinesia (LID) in animal models of Parkinson’s disease. In fact, serotonin neurons possess the enzymatic machinery able to convert exogenous l-DOPA to dopamine (DA), and mediate its vesicular storage and release. However, serotonin neurons lack a feedback control mechanism able to regulate synaptic DA levels. While in a situation of partial DA depletion spared DA terminals can buffer DA released from serotonin neurons, the progression of DA neuron degeneration impairs this protective mechanism, causing swings in synaptic DA levels and pulsatile stimulation of post-synaptic DA receptors. In line with this view, removal of serotonin neurons by selective toxin, or pharmacological silencing of their activity, produced complete suppression of LID in animal models of Parkinson’s disease. In this article, we will revise the experimental evidence pointing to the important role of serotonin neurons in dyskinesia, and we will discuss the clinical implications. PMID:24904522

N-Acetyltransferase 2 Genotypes Are Associated With Diisocyanate-Induced Asthma.

PubMed

Yucesoy, Berran; Kissling, Grace E; Johnson, Victor J; Lummus, Zana L; Gautrin, Denyse; Cartier, André; Boulet, Louis-Philippe; Sastre, Joaquin; Quirce, Santiago; Tarlo, Susan M; Cruz, Maria-Jesus; Munoz, Xavier; Luster, Michael I; Bernstein, David I

2015-12-01

To investigate whether genetic variants of N-acetyltransferase (NAT) genes are associated with diisocyanate asthma (DA). The study population consisted of 354 diisocyanate-exposed workers. Genotyping was performed using a 5'-nuclease polymerase chain reaction assay. The NAT2 rs2410556 and NAT2 rs4271002 variants were significantly associated with DA in the univariate analysis. In the first logistic regression model comparing DA+ and asymptomatic worker groups, the rs2410556 (P = 0.004) and rs4271002 (P < 0.001) single nucleotide polymorphisms and the genotype combination, NAT2 rs4271002*NAT1 rs11777998, showed associations with DA risk (P = 0.014). In the second model comparing DA+ and DA- groups, NAT2 rs4271002 variant and the combined genotype, NAT1 rs8190845*NAT2 rs13277605, were significantly associated with DA risk (P = 0.022, P = 0.036, respectively). These findings suggest that variations in the NAT2 gene and their interactions contribute to DA susceptibility.

( sup 3 H)Dopamine uptake by platelet storage granules in schizophrenia

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

Rabey, J.M.; Graff, E.; Oberman, Z.

1992-01-01

({sup 3}H)Dopamine (DA) uptake by platelet storage granules was determined in 26 schizophrenic male patients, paranoid type (14 acute stage; 12 in remission) and 20 age-matched, normal controls. maximum velocity (Vmax) of DA uptake was significantly higher in acute patients, than patients in remission or controls (p>0.05). The apparent Michaelis constant (kM) of DA uptake in acute patients was also significantly different from chronic patients a substantial diminution of DA uptake, while haloperidol produced a substantial diminution of DA uptake, while haloperidol (10{sup {minus}4}, 10{sup {minus}5} M) did not affect the assay. Considering that a DA disequilibrium in schizophrenia maymore » be expressed not only in the brain, but also in the periphery and that an increased amount of DA accumulated in the vesicles, implies that an increased quantity of catecholamine is available for release, our findings suggest additional evidence for the role of DA overactivity in the pathophysiology of this disorder.« less

Da Vinci robot-assisted system for thymectomy: experience of 55 patients in China.

PubMed

Jun, Yi; Hao, Li; Demin, Li; Guohua, Dong; Hua, Jing; Yi, Shen

2014-09-01

Da Vinci robot-assisted thymectomy has been used in the past several years in China, however, practical experience in performing this approach in China remains limited. Thus, the study aimed to evaluate the experience of da Vinci robot-assisted thymectomy in China. From June 2010 to December 2012, 55 patients with diseases of the thymus underwent thymectomy using the da Vinci surgical HD robotic system. The clinical data of the da Vinci robot-assisted thymectomies were compared with the data of video-assisted thoracoscopic thymectomies in the same period. All da Vinci robot operations were successful. This is a retrospective analysis which demonstrated that compared with video-assisted thoracoscopic thymectomy in the same period, the clinical outcomes of da Vinci robot-assisted thymectomy were not significantly different. The da Vinci robot-assisted thymectomy is a safe, minimally invasive, and convenient operation, and shows promise for general thoracic surgery in China. Copyright © 2014 John Wiley & Sons, Ltd.

Origin of the DA and non-DA white dwarf stars

NASA Technical Reports Server (NTRS)

Shipman, Harry L.

1989-01-01

Various proposals for the bifurcation of the white dwarf cooling sequence are reviewed. 'Primordial' theories, in which the basic bifurcation of the white dwarf sequence is rooted in events predating the white dwarf stage of stellar evolution, are discussed, along with the competing 'mixing' theories in which processes occurring during the white dwarf stage are responsible for the existence of DA or non-DA stars. A new proposal is suggested, representing a two-channel scenario. In the DA channel, some process reduces the hydrogen layer mass to the value of less than 10 to the -7th. The non-DA channel is similar to that in the primordial scenario. These considerations suggest that some mechanism operates in both channels to reduce the thickness of the outermost layer of the white dwarf. It is also noted that accretion from the interstellar medium has little to do with whether a particular white dwarf becomes a DA or a non-DA star.

Preformulation considerations for controlled release dosage forms. Part III. Candidate form selection using numerical weighting and scoring.

PubMed

Chrzanowski, Frank

2008-01-01

Two numerical methods, Decision Analysis (DA) and Potential Problem Analysis (PPA) are presented as alternative selection methods to the logical method presented in Part I. In DA properties are weighted and outcomes are scored. The weighted scores for each candidate are totaled and final selection is based on the totals. Higher scores indicate better candidates. In PPA potential problems are assigned a seriousness factor and test outcomes are used to define the probability of occurrence. The seriousness-probability products are totaled and forms with minimal scores are preferred. DA and PPA have never been compared to the logical-elimination method. Additional data were available for two forms of McN-5707 to provide complete preformulation data for five candidate forms. Weight and seriousness factors (independent variables) were obtained from a survey of experienced formulators. Scores and probabilities (dependent variables) were provided independently by Preformulation. The rankings of the five candidate forms, best to worst, were similar for all three methods. These results validate the applicability of DA and PPA for candidate form selection. DA and PPA are particularly applicable in cases where there are many candidate forms and where each form has some degree of unfavorable properties.

A neurocomputational account of cognitive deficits in Parkinson’s disease

PubMed Central

Hélie, Sébastien; Paul, Erick J.; Ashby, F. Gregory

2014-01-01

Parkinson’s disease (PD) is caused by the accelerated death of dopamine (DA) producing neurons. Numerous studies documenting cognitive deficits of PD patients have revealed impairments in a variety of tasks related to memory, learning, visuospatial skills, and attention. While there have been several studies documenting cognitive deficits of PD patients, very few computational models have been proposed. In this article, we use the COVIS model of category learning to simulate DA depletion and show that the model suffers from cognitive symptoms similar to those of human participants affected by PD. Specifically, DA depletion in COVIS produced deficits in rule-based categorization, non-linear information-integration categorization, probabilistic classification, rule maintenance, and rule switching. These were observed by simulating results from younger controls, older controls, PD patients, and severe PD patients in five well-known tasks. Differential performance among the different age groups and clinical populations was modeled simply by changing the amount of DA available in the model. This suggests that COVIS may not only be an adequate model of the simulated tasks and phenomena but also more generally of the role of DA in these tasks and phenomena. PMID:22683450

Morphofunctional alterations in ventral tegmental area dopamine neurons in acute and prolonged opiates withdrawal. A computational perspective.

PubMed

Enrico, P; Migliore, M; Spiga, S; Mulas, G; Caboni, F; Diana, M

2016-05-13

Dopamine (DA) neurons of the ventral tegmental area (VTA) play a key role in the neurobiological basis of goal-directed behaviors and addiction. Morphine (MOR) withdrawal induces acute and long-term changes in the morphology and physiology of VTA DA cells, but the mechanisms underlying these modifications are poorly understood. Because of their predictive value, computational models are a powerful tool in neurobiological research, and are often used to gain further insights and deeper understanding on the molecular and physiological mechanisms underlying the development of various psychiatric disorders. Here we present a biophysical model of a DA VTA neuron based on 3D morphological reconstruction and electrophysiological data, showing how opiates withdrawal-driven morphological and electrophysiological changes could affect the firing rate and discharge pattern. The model findings suggest how and to what extent a change in the balance of GABA/GLU inputs can take into account the experimentally observed hypofunction of VTA DA neurons during acute and prolonged withdrawal, whereas morphological changes may play a role in the increased excitability of VTA DA cell to opiate administration observed during opiate withdrawal. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Two Bioactive Molecular Weight Fractions of a Conditioned Medium Enhance RPE Cell Survival on Age-Related Macular Degeneration and Aged Bruch's Membrane

PubMed Central

Sugino, Ilene K.; Sun, Qian; Springer, Carola; Cheewatrakoolpong, Noounanong; Liu, Tong; Li, Hong; Zarbin, Marco A.

2016-01-01

Purpose To characterize molecular weight fractions of bovine corneal endothelial cell conditioned medium (CM) supporting retinal pigment epithelium (RPE) cell survival on aged and age-related macular degeneration (AMD) Bruch's membrane. Methods CM was subject to size separation using centrifugal filters. Retentate and filtrate fractions were tested for bioactivity by analyzing RPE survival on submacular Bruch's membrane of aged and AMD donor eyes and behavior on collagen I-coated tissue culture wells. Protein and peptide composition of active fractions was determined by mass spectrometry. Results Two bioactive fractions, 3-kDa filtrate and a 10-50–kDa fraction, were necessary for RPE survival on aged and AMD Bruch's membrane. The 3-kDa filtrate, but not the 10-50–kDa fraction, supported RPE growth on collagen 1‐coated tissue culture plates. Mass spectrometry of the 10-50–kDa fraction identified 175 extracellular proteins, including growth factors and extracellular matrix molecules. Transforming growth factor (TGF)β-2 was identified as unique to active CM. Peptides representing 29 unique proteins were identified in the 3-KDa filtrate. Conclusions These results indicate there is a minimum of two bioactive molecules in CM, one found in the 3-kDa filtrate and one in the 10-50–kDa fraction, and that bioactive molecules in both fractions must be present to ensure RPE survival on Bruch's membrane. Mass spectrometry analysis suggested proteins to test in future studies to identify proteins that may contribute to CM bioactivity. Translational Relevance Results of this study are the first steps in development of an adjunct to cell-based therapy to ensure cell transplant survival and functionality in AMD patients. PMID:26933521

Culture and Dehydration: A Comparative Study of Caída de la Mollera (Fallen Fontanel) in Three Latino Populations.

PubMed

Pachter, Lee M; Weller, Susan C; Baer, Roberta D; de Alba Garcia, Javier E Garcia; Glazer, Mark; Trotter, Robert; Klein, Robert E; Gonzalez, Eduardo

2016-10-01

A sunken soft-spot or fontanel is a sign for dehydration in infants. Around the world, folk illnesses, such as caída de la mollera in some Latin American cultures, often incorporate this sign as a hallmark of illness, but may or may not incorporate re-hydration therapies in treatment strategies. This report describes a study of lay descriptions of causes, symptoms, and treatments for caída de la mollera in three diverse Latin American populations. A mixed-methods approach was used. Representative community-based samples were interviewed in rural Guatemala, Guadalajara, Mexico, and Edinburgh, Texas, with a 132 item questionnaire on the causes, susceptibility, symptoms, and therapies for caída de la mollera. Cultural consensus analysis was used to estimate community beliefs about caída. Interviews conducted in rural Guatemala (n = 60), urban Mexico (n = 62), and rural Texas on the Mexican border (n = 61) indicated consistency in thematic elements within and among these three diverse communities. The high degree of consistency in the illness explanatory models indicated shared beliefs about caída de la mollera in each of the communities and a core model shared across communities. However, an important aspect of the community beliefs was that rehydration therapies were not widely endorsed. The consistency in explanatory models in such diverse communities, as well as the high degree of recognition and experience with this illness, may facilitate communication between community members, and health care providers/public health intervention planners to increase use of rehydration therapies for caída de la mollera. Recommendations for culturally informed and respectful approaches to clinical communication are provided.

The effects of nicotine exposure and PFC transection on the time-frequency distribution of VTA DA neurons' firing activities.

PubMed

Chen, Ting Y; Zhang, Die; Dragomir, Andrei; Akay, Yasemin; Akay, Metin

2011-05-01

We investigated the influence of nicotine exposure and prefrontal cortex (PFC) transections on ventral tegmental areas (VTA) dopamine (DA) neurons' firing activities using a time-frequency method based on the continuous wavelet transform (CWT). Extracellular single-unit neural activity was recorded from DA neurons in the VTA area of rats. One group had their PFC inputs to the VTA intact, while the other group had the inputs to VTA bilaterally transected immediate caudal to the PFC. We hypothesized that the systemic nicotine exposure will significantly change the energy distribution in the recorded neural activity. Additionally, we investigated whether the loss of inputs to the VTA caused by the PFC transection resulted in the cancellation of the nicotine' effect on the neurons' firing patterns. The time-frequency representations of VTA DA neurons firing activity were estimated from the reconstructed firing rate histogram. The energy contents were estimated from three frequency bands, which are known to encompass the significant modes of operation of DA neurons. Our results show that systemic nicotine exposure disrupts the energy distribution in PFC-intact rats. Particularly, there is a significant increase in energy contents of the 1-1.5 Hz frequency band. This corresponds to an observed increase in the firing rate of VTA DA neurons following nicotine exposure. Additionally, our results from PFC-transected rats show that there is no change in the energy distribution of the recordings after systemic nicotine exposure. These results indicate that the PFC plays an important role in affecting the activities of VTA DA neurons and that the CWT is a useful method for monitoring the changes in neural activity patterns in both time and frequency domains.

Selective inhibition of dopamine-beta-hydroxylase enhances dopamine release from noradrenergic terminals in the medial prefrontal cortex.

PubMed

Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Frau, Roberto; Gessa, Gian L

2015-10-01

Disulfiram has been claimed to be useful in cocaine addiction therapy, its efficacy being attributed to dopamine-beta-hydroxylase (DBH) inhibition. Our previous results indicate that disulfiram and the selective DBH inhibitor nepicastat increase extracellular dopamine (DA) in the rat medial prefrontal cortex (mPFC), and markedly potentiated cocaine-induced increase. Concomitantly, in rats with cocaine self-administration history, cocaine-seeking behavior induced by drug priming was prevented, probably through overstimulation of D1 receptors due to the DA increase. The present research was aimed at studying the neurochemical mechanisms originating the enhanced DA release. Noradrenergic system ablation was attained by intracerebroventricular (i.c.v.) administration of the neurotoxin anti-DBH-saporin (aDBH-sap). DA, noradrenaline (NA), and DOPAC were assessed by HPLC after ex vivo tissue extraction or in vivo microdialysis. Control and denervated rats were subjected to microdialysis in the mPFC and caudate nucleus to evaluate the effect of nepicastat-cocaine combination on extracellular DA levels and their regulation by α2-adrenoceptors. Fifteen days after neurotoxin or its vehicle administration, tissue and extracellular NA were reduced to less than 2% the control value, while extracellular DA was increased by approximately 100%. In control rats, nepicastat given alone and in combination with cocaine increased extracellular DA by about 250% and 1100%, respectively. In denervated rats, nepicastat slightly affected extracellular DA, while in combination with cocaine increased extracellular DA by 250%. No differences were found in the caudate nucleus. Clonidine almost totally reversed the extracellular DA elevation produced by nepicastat-cocaine combination, while it was ineffective in denervated rats. This research shows that the increase of extracellular DA produced by nepicastat alone or in combination with cocaine was prevented by noradrenergic denervation. The results indicate that nepicastat enhances DA release from noradrenergic terminals supposedly by removing NA from α2-autoreceptors. In addition to the inhibition of DA uptake, the latter mechanism may explain the synergistic effect of cocaine on nepicastat-induced DA release.

Cloning and functional characterization of the DA2 receptor gene in Chinese mitten crab (Eriocheir sinensis)

PubMed Central

Xu, Min-jie; Zhang, Cong; Yang, Zhigang

2018-01-01

Dopamine (DA) plays a modulatory role in numerous physiological processes such as light adaptation and food intake, and exerts these functions through DA receptors (DARs). This study presents, for the first time, isolation and characterization of the dopamine receptor 2(DA2 receptor) cDNA from the intestinal tissue of Eriocheir sinensis, an economically important freshwater aquaculture species in China. The DA2 receptor cDNA sequence, which was obtained by rapid amplification of cDNA ends, is 2369bp long, encode peptide of 589 amino acid, and is highly homologous to related sequences in crustaceans. Analysis of the deduced amino acid sequence and the structure of the DA2 indicated that this receptor is a member of the family of G protein-coupled receptors (GPCRs), as it contains seven transmembrane domains and other common signatures of GPCRs. RT-PCR showed that the expression of the DA2 receptor gene was distributed in various tissues, and high expression levels were observed in the cranial ganglia and the thoracic ganglia. Further study of the effect of photoperiod on DA2 expression showed that constant darkness induced a significant increase in DA2 expression in the cranial ganglia. Finally, analysis of DA2 receptor expression under different feeding statuses showed that there was significantly greater expression in the hepatopancreas and intestines after feeding than before feeding, but there were no differences in expression between the before feeding and during feeding periods in either tissue. Our results indicate that the DA2 receptor structurally belongs to the family of G protein-coupled receptors, and that the cranial ganglia are the main tissues in which the DA2 receptor participates in light adaptation during dark hours. In addition, the DA2 receptor in E. sinensis may be involved in the physiological regulation of the hepatopancreas and digestive tract after the ingestion of food. This study provides a foundation for further exploration of the light adaptation and digestive functions of the DA2 receptor in decapods. PMID:29554147

Antimonide-Based Compound Semiconductors for Low-Power Electronics

DTIC Science & Technology

2013-01-01

A, Madan HS, Kirk AP, Zhao DA, Mourey DA, Hudait MK, et al. Fermi level unpinning of GaSb (100) using plasma enhanced atomic layer deposition of...et al. Atomic layer deposition of Al2O3 on GaSb using in situ hydrogen plasma exposure. Appl Phys Lett. 2012;101: 231601. [18] Ali A, Madan H

The Impact of a Three-Year Teacher Professional Development Course on Quality of Teaching: Strengths and Limitations of the Dynamic Approach

ERIC Educational Resources Information Center

Kyriakides, L.; Christoforidou, M.; Panayiotou, A.; Creemers, B. P. M.

2017-01-01

The dynamic approach (DA) suggests that professional development should be differentiated to meet teachers' individual needs while engaging participants into systematic and guided critical reflection. Previous experimental studies demonstrated that one-year interventions based on the DA have a positive impact on teacher effectiveness. The study…

Biosynthesis and intracellular transport of the receptor for platelet-derived growth factor.

PubMed Central

Claesson-Welsh, L; Rönnstrand, L; Heldin, C H

1987-01-01

The biosynthesis of the receptor for platelet-derived growth factor (PDGF) was examined in metabolically labeled human foreskin fibroblasts. The receptor was synthesized as a 145-kDa precursor, which, when incubated with endo-beta-N-acetylglucosaminidase H (endo H), underwent a 15-kDa decrease in molecular mass. This indicates that the size of the core protein is about 130 kDa and that the 145-kDa form represents a receptor precursor carrying high-mannose N-linked oligosaccharide groups. Within 15 min after synthesis, the receptor was converted to a 165-kDa form. This form was entirely resistant to endo H treatment and probably represents a receptor molecule that has undergone further posttranslational modification, including O-linked glycosylation. Subsequently, within 30 min, a molecule of 170 kDa--i.e., the size of the mature receptor--appeared. A slightly larger molecule, of 175 kDa, which could be immunoprecipitated from PDGF-stimulated 32P-labeled cells, probably represents a receptor further modified by autophosphorylation. The 170-kDa molecule had an isoelectric point of about 4.5. Addition of PDGF increased the turnover rate of the 170-kDa PDGF receptor. Images PMID:2827155

Estudo em microondas do aprisionamento e precipitação de elétrons em explosões solares

NASA Astrophysics Data System (ADS)

Rosal, A. C.; Costa, J. E. R.

2003-08-01

Uma explosão solar é uma variação rápida e intensa do brilho que ocorre nas chamadas regiões ativas da atmosfera, constituídas por um plasma magnetizado com intensa indução magnética. Os modelos de explosões solares atuais, discutidos na literatura, apresentam características de aprisionamento e precipitação de elétrons em ambientes magnéticos simplificados. Neste trabalho, nos propusemos a separar a emissão dos elétrons aprisionados da emissão dos elétrons em precipitação apenas a partir da emissão em microondas, melhorando portanto o controle sobre o conjunto de parâmetros inferidos. A emissão em microondas da população em precipitação é bastante fraca e portanto da nossa base de dados de 130 explosões observadas pelo Rádio Polarímetro de Nobeyama, em sete freqüências, apenas para 32 foi possível separar as duas componentes de emissão com uma boa razão sinal/ruído. A partir de estudos das escalas de tempo das emissões devidas à variação gradual da emissão no aprisionamento e da variação rápida da emissão dos elétrons em precipitação foi possível obter a separação utilizando um filtro temporal nas emissões resultantes. Em nossa análise destas explosões estudamos os espectros girossincrotrônicos da emissão gradual, a qual associamos provir do topo dos arcos magnéticos e da emissão de variação rápida associada aos elétrons em precipitação. Estes espectros foram calculados e dos quais inferimos que a indução magnética efetiva do topo e dos pés foi em média, Btopo = 236 G e Bpés = 577 G, inferidas das freqüências de pico dos espectros em ntopo = 11,8 GHz e npés = 14,6 GHz com leve anisotropia (pequeno alargamento espectral). O índice espectral da distribuição não-térmica de elétrons d, inferido do índice espectral de fótons da emissão em regime opticamente fino, foi de dtopo = 3,3 e dpés = 3,9. Estes parâmetros são típicos da maioria das análises realizadas em ambiente único de emissão e a relação dos índices espectrais, dpés > dtopo prioriza as interpretações com difusão em ângulo de passo devida a colisões Coulombianas. Nesta difusão o déficit de elétrons energéticos na precipitação seria uma conseqüência natural da dependência em e-3/2 das colisões elétron-próton (onde e é a energia dos elétrons).

Persistent Adaptations in Afferents to Ventral Tegmental Dopamine Neurons after Opiate Withdrawal.

PubMed

Kaufling, Jennifer; Aston-Jones, Gary

2015-07-15

Protracted opiate withdrawal is accompanied by altered responsiveness of midbrain dopaminergic (DA) neurons, including a loss of DA cell response to morphine, and by behavioral alterations, including affective disorders. GABAergic neurons in the tail of the ventral tegmental area (tVTA), also called the rostromedial tegmental nucleus, are important for behavioral responses to opiates. We investigated the tVTA-VTA circuit in rats after chronic morphine exposure to determine whether tVTA neurons participate in the loss of opiate-induced disinhibition of VTA DA neurons observed during protracted withdrawal. In vivo recording revealed that VTA DA neurons, but not tVTA GABAergic neurons, are tolerant to morphine after 2 weeks of withdrawal. Optogenetic stimulation of tVTA neurons inhibited VTA DA neurons similarly in opiate-naive and long-term withdrawn rats. However, tVTA inactivation increased VTA DA activity in opiate-naive rats, but not in withdrawn rats, resembling the opiate tolerance effect in DA cells. Thus, although inhibitory control of DA neurons by tVTA is maintained during protracted withdrawal, the capacity for disinhibitory control is impaired. In addition, morphine withdrawal reduced both tVTA neural activity and tonic glutamatergic input to VTA DA neurons. We propose that these changes in glutamate and GABA inputs underlie the apparent tolerance of VTA DA neurons to opiates after chronic exposure. These alterations in the tVTA-VTA DA circuit could be an important factor in opiate tolerance and addiction. Moreover, the capacity of the tVTA to inhibit, but not disinhibit, DA cells after chronic opiate exposure may contribute to long-term negative affective states during withdrawal. Dopaminergic (DA) cells of the ventral tegmental area (VTA) are the origin of a brain reward system and are critically involved in drug abuse. Morphine has long been known to affect VTA DA cells via GABAergic interneurons. Recently, GABAergic neurons caudal to the VTA were discovered and named the tail of VTA (tVTA). Here, we show that tVTA GABA neurons lose their capacity to disinhibit, but not to inhibit, VTA DA cells after chronic opiate exposure. The failure of disinhibition was associated with a loss of glutamatergic input to DA neurons after chronic morphine. These findings reveal mechanisms by which the tVTA may play a key role in long-term negative affective states during opiate withdrawal. Copyright © 2015 the authors 0270-6474/15/3510290-14$15.00/0.

Enhanced Dopamine Detection Sensitivity by PEDOT/Graphene Oxide Coating on in vivo Carbon Fiber Electrodes

PubMed Central

Taylor, I. Mitch; Robbins, Elaine M.; Catt, Kasey A.; Cody, Patrick A.; Weaver, Cassandra L.; Cui, Xinyan Tracy

2016-01-01

Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA’s oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo. PMID:27268013

Evidence for a dopamine intrinsic direct role in the regulation of the ovary reproductive function: in vitro study on rabbit corpora lutea.

PubMed

Parillo, Francesco; Maranesi, Margherita; Mignini, Fiorenzo; Marinelli, Lisa; Di Stefano, Antonio; Boiti, Cristiano; Zerani, Massimo

2014-01-01

Dopamine (DA) receptor (DR) type 1 (D1R) has been found to be expressed in luteal cells of various species, but the intrinsic role of the DA/DRs system on corpora lutea (CL) function is still unclear. Experiments were devised to characterize the expression of DR types and the presence of DA, as well as the in vitro effects of DA on hormone productions by CL in pseudopregnant rabbits. Immunoreactivity and gene expression for D1R decreased while that for D3R increased in luteal and blood vessel cells from early to late pseudopregnant stages. DA immunopositivity was evidenced only in luteal cells. The DA and D1R agonist increased in vitro release of progesterone and prostaglandin E2 (PGE2) by early CL, whereas the DA and D3R agonist decreased progesterone and increased PGF2α in vitro release by mid- and late CL. These results provide evidence that the DA/DR system exerts a dual modulatory function in the lifespan of CL: the DA/D1R is luteotropic while the DA/D3R is luteolytic. The present data shed new light on the physiological mechanisms regulating luteal activity that might improve our ability to optimize reproductive efficiency in mammal species, including humans.

Effectivity of immunostimulant from Zoothamnium penaei protein membrane for decreasing the mortality rate of white shrimp (Litopenaeus vannamei) in traditional plus pond

NASA Astrophysics Data System (ADS)

Mahasri, G.; Kusdarwati, R.; Kismiyati; Rozi; Gustrifandi, H.

2018-04-01

The purpose of this research was to analys immunogenic membrane protein as immunostimulant development material to control the mortality of white shrimp in traditional plus pond. This research was designed to use explorative experiment and experimental laboratory methods which used completed random sampling design. Collected data was analyzed with analysis of variance for examination of survival rate (SR), total haemocyte count (THC) and differensial haemocyte Count (DHC). The research divided into 2 part of riset: (1) Identification, cultivation Zoothamnium penaei, analysed of membrane protein by SDS-PAGE, (2) Field test protein membran on Survival Rate level, immune response (THC and/or DHC level) and infestation of Zoothamnium penaei in traditional plus pond. The result showed that there were seven bands membrane protein of Zoothamnium penaei with molecular weight 38 kDa, 48 kDa, 67 kDa, 71 kDa, 77 kDa, 98 kDa dan 104 kDa by using SDS-PAGE. Immunogenicity tested decrease by using ELISA and western blotting there are only found three bands with molecular weight 38 kDa, 48 kDa dan 67 kDa. The membrane protein could increase the immun respons and decrease the mortality, by subsequenly, it could increase the survival rate from 17% until 68% and pressured the parasite infestation of white shrimp.

The 29-kDa proteins phosphorylated ion thrombin-activated human platelets are forms of the estrogen receptor-related 27-kDa heat shock protein

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

Mendelsohn, M.E.; Yan Zhu; O'Neill, S.

Thrombin plays a critical role in platelet activation, hemostasis, and thrombosis. Cellular activation by thrombin leads to the phosphorylation of multiple proteins, most of which are unidentified. The authors have characterized several 29-kDa proteins that are rapidly phosphorylated following exposure of intact human platelets to thrombin. A murine monoclonal antibody raised to an unidentified estrogen receptor-related 29-kDa protein selectively recognized these proteins as well as a more basic, unphosphorylated 27-kDa protein. Cellular activation by thrombin led to a marked shift in the proportion of protein from the 27-kDa unphosphorylated form to the 29-kDa phosphoprotein species. Using this antibody, they isolatedmore » and sequenced a human cDNA clone encoding a protein that was identical to the mammalian 27-kDa heat shock protein (HSP27), a protein of uncertain function that is known to be phosphorylated to several forms and to be transcriptionally induced by estrogen. The 29-kDa proteins were confirmed to be phosphorylated forms of HSP27 by immunoprecipitation studies. Thus, the estrogen receptor-related protein is HSP27, and the three major 20-kDa proteins phosphorylated in thrombin-activated platelets are forms of HSP27. These data suggest a role for HSP27 in the signal transduction events of platelet activation.« less

The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants.

PubMed

Mergy, Marc A; Gowrishankar, Raajaram; Gresch, Paul J; Gantz, Stephanie C; Williams, John; Davis, Gwynne L; Wheeler, C Austin; Stanwood, Gregg D; Hahn, Maureen K; Blakely, Randy D

2014-11-04

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness.

Preclinical and Clinical Studies Demonstrate That the Proprietary Herbal Extract DA-5512 Effectively Stimulates Hair Growth and Promotes Hair Health.

PubMed

Yu, Jae Young; Gupta, Biki; Park, Hyoung Geun; Son, Miwon; Jun, Joon-Ho; Yong, Chul Soon; Kim, Jeong Ah; Kim, Jong Oh

2017-01-01

The proprietary DA-5512 formulation comprises six herbal extracts from traditional oriental plants historically associated with therapeutic and other applications related to hair. Here, we investigated the effects of DA-5512 on the proliferation of human dermal papilla cells (hDPCs) in vitro and on hair growth in C57BL/6 mice and conducted a clinical study to evaluate the efficacy and safety of DA-5512. DA-5512 significantly enhanced the viability of hDPCs in a dose-dependent manner ( p < 0.05), and 100 ppm of DA-5512 and 1  μ M minoxidil (MXD) significantly increased the number of Ki-67-positive cells, compared with the control group ( p < 0.05). MXD (3%) and DA-5512 (1%, 5%) significantly stimulated hair growth and increased the number and length of hair follicles (HFs) versus the controls (each p < 0.05). The groups treated with DA-5512 exhibited hair growth comparable to that induced by MXD. In clinical study, we detected a statistically significant increase in the efficacy of DA-5512 after 16 weeks compared with the groups treated with placebo or 3% MXD ( p < 0.05). In conclusion, DA-5512 might promote hair growth and enhance hair health and can therefore be considered an effective option for treating hair loss.

The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants

PubMed Central

Mergy, Marc A.; Gowrishankar, Raajaram; Gresch, Paul J.; Gantz, Stephanie C.; Williams, John; Davis, Gwynne L.; Wheeler, C. Austin; Stanwood, Gregg D.; Hahn, Maureen K.; Blakely, Randy D.

2014-01-01

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness. PMID:25331903

Effects of DA-Phen, a dopamine-aminoacidic conjugate, on alcohol intake and forced abstinence.

PubMed

Sutera, Flavia Maria; De Caro, Viviana; Cannizzaro, Carla; Giannola, Libero Italo; Lavanco, Gianluca; Plescia, Fulvio

2016-09-01

The mesolimbic dopamine (DA) system plays a key role in drug reinforcement and is involved in the development of alcohol addiction. Manipulation of the DAergic system represents a promising strategy to control drug-seeking behavior. Previous studies on 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) showed in vivo effects as a DA-ergic modulator. This study was aimed at investigate DA-Phen effects on operant behavior for alcohol seeking behavior, during reinstatement following subsequent periods of alcohol deprivation. For this purpose, male Wistar rats were tested in an operant paradigm of self-administration; behavioral reactivity and anxiety like-behavior during acute abstinence were evaluated. A characterization of DA-Phen CNS targeting by its quantification in the brain was also carried out. Our findings showed that DA-Phen administration was able to reduce relapse in alcohol drinking by 50% and reversed the alterations in behavioral reactivity and emotionality observed during acute abstinence. In conclusion, DA-Phen can reduce reinstatement of alcohol drinking in an operant-drinking paradigm following deprivation periods and reverse abstinence-induced behavioral phenotype. DA-Phen activity seems to be mediated by the modulation of the DAergic transmission. However further studies are needed to characterize DA-Phen pharmacodynamic and pharmacokinetic properties, and its potential therapeutic profile in alcohol addiction. Copyright © 2016 Elsevier B.V. All rights reserved.

Vinpocetine and α-tocopherol prevent the increase in DA and oxidative stress induced by 3-NPA in striatum isolated nerve endings.

PubMed

Herrera-Mundo, Nieves; Sitges, María

2013-01-01

Vinpocetine is a neuroprotective drug that exerts beneficial effects on neurological symptoms and cerebrovascular disease. 3-nitropropionic acid (3-NPA) is a toxin that irreversibly inhibits succinate dehydrogenase, the mitochondrial enzyme that acts in the electron transport chain at complex II. In previous studies in striatum-isolated nerve endings (synaptosomes), we found that vinpocetine decreased dopamine (DA) at expense of its main metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), and that 3-NPA increased DA, reactive oxygen species (ROS), DA-quinone products formation, and decreased DOPAC. Therefore, in this study, the possible effect of vinpocetine on 3-NPA-induced increase in DA, ROS, lipid peroxidation, and DA-quinone products formation in striatum synaptosomes were investigated, and compared with the effects of the antioxidant α-tocopherol. Results show that the increase in DA induced by 3-NPA was inhibited by both 25 μM vinpocetine and 50 μM α-tocopherol. Vinpocetine, as α-tocopherol, also inhibited 3-NPA-induced increase in ROS (as judged by DCF fluorescence), lipid peroxidation (as judged by TBA-RS formation), and DA-quinone products formation (as judged by the nitroblue tetrazolium reduction method). As in addition to the inhibition of complex II exerted by 3-NPA, 3-NPA increases DA-oxidation products that in turn can inhibit other sites of the respiratory chain, the drop in DA produced by vinpocetine and α-tocopherol may importantly contribute to their protective action from oxidative damage, particularly in DA-rich structures. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.

An isoform of myosin XI is responsible for the translocation of endoplasmic reticulum in tobacco cultured BY-2 cells.

PubMed

Yokota, Etsuo; Ueda, Shunpei; Tamura, Kentaro; Orii, Hidefumi; Uchi, Satoko; Sonobe, Seiji; Hara-Nishimura, Ikuko; Shimmen, Teruo

2009-01-01

The involvement of myosin XI in generating the motive force for cytoplasmic streaming in plant cells is becoming evident. For a comprehensive understanding of the physiological roles of myosin XI isoforms, it is necessary to elucidate the properties and functions of each isoform individually. In tobacco cultured BY-2 cells, two types of myosins, one composed of 175 kDa heavy chain (175 kDa myosin) and the other of 170 kDa heavy chain (170 kDa myosin), have been identified biochemically and immunocytochemically. From sequence analyses of cDNA clones encoding heavy chains of 175 kDa and 170 kDa myosin, both myosins have been classified as myosin XI. Immunocytochemical studies using a polyclonal antibody against purified 175 kDa myosin heavy chain showed that the 175 kDa myosin is distributed throughout the cytoplasm as fine dots in interphase BY-2 cells. During mitosis, some parts of 175 kDa myosin were found to accumulate in the pre-prophase band (PPB), spindle, the equatorial plane of a phragmoplast and on the circumference of daughter nuclei. In transgenic BY-2 cells, in which an endoplasmic reticulum (ER)-specific retention signal, HDEL, tagged with green fluorescent protein (GFP) was stably expressed, ER showed a similar behaviour to that of 175 kDa myosin. Furthermore, this myosin was co-fractionated with GFP-ER by sucrose density gradient centrifugation. From these findings, it was suggested that the 175 kDa myosin is a molecular motor responsible for translocating ER in BY-2 cells.

Tonic dopamine induces persistent changes in the transient potassium current through translational regulation

PubMed Central

Rodgers, EW; Krenz, W-D; Baro, DJ

2012-01-01

Neuromodulatory effects can vary with their mode of transmission. Phasic release produces local and transient increases in dopamine (DA) up to micromolar concentrations. Additionally, since DA is released from open synapses and reuptake mechanisms are not nearby, tonic nanomolar DA exists in the extracellular space. Do phasic and tonic transmissions similarly regulate voltage dependent ionic conductances in a given neuron? It was previously shown that DA could immediately alter the transient potassium current (IA) of identified neurons in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus. Here we show that DA can also persistently alter IA, and that DA’s immediate and persistent effects oppose one another. The lateral pyloric neuron (LP) exclusively expresses type 1 DA receptors (D1Rs). Micromolar DA produces immediate depolarizing shifts in the voltage dependence of LP IA, whereas tonic nanomolar DA produces a persistent increase in LP IA maximal conductance (Gmax) through a translation dependent mechanism involving target of rapamycin (TOR). The pyloric dilator neuron (PD) exclusively expresses type 2 DA receptors (D2Rs). Micromolar DA produces an immediate hyperpolarizing shift in PD IA voltage dependence of activation, whereas tonic DA persistently decreases PD IA Gmax through a translation dependent mechanism not involving TOR. The persistent effects on IA Gmax do not depend on LP or PD activity. These data suggest a role for tonic modulators in the regulation of voltage gated ion channel number; and furthermore, that dopaminergic systems may be organized to limit the amount of change they can impose on a circuit. PMID:21917788

Increases in cytoplasmic dopamine compromise the normal resistance of the nucleus accumbens to methamphetamine neurotoxicity

PubMed Central

Thomas, David M.; Francescutti-Verbeem, Dina M.; Kuhnt, Donald M.

2016-01-01

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the caudate–putamen (CPu) where long-term DA depletion and microglial activation are most evident. Even damage within the CPu is remarkably heterogenous with lateral and ventral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared of the damage that accompanies binge METH intoxication. Increases in cytoplasmic DA produced by reserpine, L-DOPA or clorgyline prior to METH uncover damage in the NAc as evidenced by microglial activation and depletion of DA, tyrosine hydroxylase (TH), and the DA transporter. These effects do not occur in the NAc after treatment with METH alone. In contrast to the CPu where DA, TH, and DA transporter levels remain depleted chronically, DA nerve ending alterations in the NAc show a partial recovery over time. None of the treatments that enhance METH toxicity in the NAc and CPu lead to losses of TH protein or DA cell bodies in the substantia nigra or the ventral tegmentum. These data show that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of METH to include brain structures not normally targeted for damage by METH alone. The resistance of the NAc to METH-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of METH neurotoxicity by alterations in DA homeostasis is significant in light of the important roles played by this brain structure. PMID:19457119

Pharmacological action of DA-9701 on the motility of feline stomach circular smooth muscle.

PubMed

Nguyen, Thanh Thao; Song, Hyun Ju; Ko, Sung Kwon; Sohn, Uy Dong

2015-03-01

DA-9701, a new prokinetic agent for the treatment of functional dyspepsia, is formulated with Pharbitis semen and Corydalis tuber. This study wasconducted to determine the pharmacological action of DA-9701 and to identify the receptors involved in DA-9701 -induced contractile responsesin the feline gastric corporal, fundic and antral circular smooth muscle. Concentration-response curve to DA-9701 was established. The tissue trips were exposed to methylsergide, ketanserin, ondansetron, GR 113808, atropine and dopamine before administration of DA-9701. The contractile force was determined before and after administration of drugs by a polygraph.DA-9701 enhanced the spontaneous contractile amplitude of antrum, corpus and fundus. However, it did not change the spontaneous contractile frequency of antrum and corpus, but concentration-dependently reduced that of fundus. In the fundus, DA-9701 -induced tonic contractions were inhibited by dopamine, methylsergide, ketanserine, ondansetron or GR 113808 respectively, but not by atropine, indicating that the contractile responses are mediated by multiple receptors: 5-HT2, 5-HT3, 5-HT4, and dopamine receptors. In the corpus, DA-9701-induced contractions were blocked by atropine, dopamine or GR 113808, but not by methysergide, ketanserin or ondansetron, indicating that they are involved in receptors on both, smooth muscles and neurons: 5-HT4 and dopamine receptors. However, contractile responses to DA-9701 are mainly mediated by dopamine receptors in the antrum. These results suggest that DA-9701 has important roles in gastric accommodation by enhancing tonic activity of fundus, and in gastric emptying and gastrointestinal transit by phasic contractions of corpus and antrum mediated by multiple receptors.

Increases in cytoplasmic dopamine compromise the normal resistance of the nucleus accumbens to methamphetamine neurotoxicity.

PubMed

Thomas, David M; Francescutti-Verbeem, Dina M; Kuhn, Donald M

2009-06-01

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the caudate-putamen (CPu) where long-term DA depletion and microglial activation are most evident. Even damage within the CPu is remarkably heterogenous with lateral and ventral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared of the damage that accompanies binge METH intoxication. Increases in cytoplasmic DA produced by reserpine, L-DOPA or clorgyline prior to METH uncover damage in the NAc as evidenced by microglial activation and depletion of DA, tyrosine hydroxylase (TH), and the DA transporter. These effects do not occur in the NAc after treatment with METH alone. In contrast to the CPu where DA, TH, and DA transporter levels remain depleted chronically, DA nerve ending alterations in the NAc show a partial recovery over time. None of the treatments that enhance METH toxicity in the NAc and CPu lead to losses of TH protein or DA cell bodies in the substantia nigra or the ventral tegmentum. These data show that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of METH to include brain structures not normally targeted for damage by METH alone. The resistance of the NAc to METH-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of METH neurotoxicity by alterations in DA homeostasis is significant in light of the important roles played by this brain structure.

Methylphenidate and Cocaine Self-Administration Produce Distinct Dopamine Terminal Alterations

PubMed Central

Calipari, Erin S.; Ferris, Mark J.; Melchior, James R.; Bermejo, Kristel; Salahpour, Ali; Roberts, David C. S.; Jones, Sara R.

2012-01-01

Methylphenidate (MPH) is a commonly abused psychostimulant prescribed for the treatment of attention deficit hyperactivity disorder. MPH has a mechanism of action similar to cocaine (COC) and is commonly characterized as a dopamine transporter (DAT) blocker. While there has been extensive work aimed at understanding dopamine (DA) nerve terminal changes following COC self-administration, very little is known about the effects of MPH self-administration on the DA system. We used fast scan cyclic voltammetry in nucleus accumbens core slices from animals with a five-day self-administration history of 40 injections/day of either MPH (0.56 mg/kg) or COC (1.5 mg/kg) to explore alterations in baseline DA release and uptake kinetics as well as alterations in the interaction of each compound with the DAT. Although MPH and COC have similar behavioral effects, the consequences of self-administration on DA system parameters were found to be divergent. We show that COC self-administration reduced DAT levels and maximal rates of DA uptake, as well as reducing electrically stimulated release, suggesting decreased DA terminal function. In contrast, MPH self-administration increased DAT levels, DA uptake rates, and DA release, suggesting enhanced terminal function, which was supported by findings of increased metabolite/DA tissue content ratios. Tyrosine hydroxylase mRNA, protein and phosphorylation levels were also assessed in both groups. Additionally, COC self-administration reduced COC-induced DAT inhibition, while MPH self-administration increased MPH-induced DAT inhibition, suggesting opposite pharmacodynamic effects of these two drugs. These findings suggest that the factors governing DA system adaptations are more complicated than simple DA uptake blockade. PMID:22458761

A top-down perspective on dopamine, motivation and memory.

PubMed

Phillips, Anthony G; Vacca, Giada; Ahn, Soyon

2008-08-01

Dopamine (DA) activity, in the form of increased neural firing or enhanced release of transmitter from nerve terminals and varicosities, is linked to a number of important psychological processes including: movement; hedonic reactions to positive reward; provision of an error detection signal during the acquisition of new learning; response to novel stimuli; provision of reinforcement signals essential for acquisition of new action patterns; and incentive motivation. This review focuses primarily on our research linking dynamic changes in DA efflux on the timescale of minutes, with incentive motivation, as revealed by brain dialysis experiments in behaving animals. Recent experiments on sensory-specific satiety and successive positive and negative contrast are discussed along with the distinction between preparatory behaviors that precede contact with biologically significant stimuli and subsequent consummatory behaviors. The relationship between DA efflux in the medial prefrontal cortex (mPFC) and foraging for food based on working memory is also discussed in support of the conjecture that DA may serve as a link between motivation and memory functions. Evidence in support of 'top-down' regulation of dopaminergic activity in the mesocorticolimbic DA pathways is reviewed briefly to introduce a mechanism by which activation of ascending DA projections in this manner might optimize dopaminergic modulation of executive function within regions such as the mPFC. Collectively, these processes could ensure coordination between cognitive processes that assess current opportunities and the motivational systems that select and engage patterns of approach behavior that bring organisms into contact with the essentials for survival.

A plastic corticostriatal circuit model of adaptation in perceptual decision making

PubMed Central

Hsiao, Pao-Yueh; Lo, Chung-Chuan

2013-01-01

The ability to optimize decisions and adapt them to changing environments is a crucial brain function that increase survivability. Although much has been learned about the neuronal activity in various brain regions that are associated with decision making, and about how the nervous systems may learn to achieve optimization, the underlying neuronal mechanisms of how the nervous systems optimize decision strategies with preference given to speed or accuracy, and how the systems adapt to changes in the environment, remain unclear. Based on extensive empirical observations, we addressed the question by extending a previously described cortico-basal ganglia circuit model of perceptual decisions with the inclusion of a dynamic dopamine (DA) system that modulates spike-timing dependent plasticity (STDP). We found that, once an optimal model setting that maximized the reward rate was selected, the same setting automatically optimized decisions across different task environments through dynamic balancing between the facilitating and depressing components of the DA dynamics. Interestingly, other model parameters were also optimal if we considered the reward rate that was weighted by the subject's preferences for speed or accuracy. Specifically, the circuit model favored speed if we increased the phasic DA response to the reward prediction error, whereas the model favored accuracy if we reduced the tonic DA activity or the phasic DA responses to the estimated reward probability. The proposed model provides insight into the roles of different components of DA responses in decision adaptation and optimization in a changing environment. PMID:24339814

Resultados a longo prazo da angioplastia de artérias renais com stent na doença aterosclerótica: revisão sistemática

PubMed Central

Siqueira, Daniel Emilio Dalledone; Guillaumon, Ana Terezinha

2017-01-01

Resumo A doença renovascular aterosclerótica é a principal causa de hipertensão secundária. A história natural da doença demonstra taxas de progressão de 4 a 12% ao ano. Entre os métodos de tratamento existe a angioplastia com stent de artérias renais; porém, poucos estudos clínicos demonstraram seus resultados a longo prazo. Esta revisão sistemática da literatura se propõe a apresentar os resultados a longo prazo (acima de 24 meses) da angioplastia com stent de artérias renais na doença aterosclerótica em relação à função renal e aos níveis pressóricos no controle da hipertensão. Foi realizada uma ampla pesquisa, utilizando os termos apropriados, nas bases de dados LILACS, EMBASE, SCIELO, Cochrane Library e MEDLINE. De um total de 2.170 referências, apenas sete artigos contemplavam todos os critérios de inclusão. Conclui-se que, a longo prazo, há uma estabilização da função renal, redução dos níveis pressóricos e diminuição do número de classes de medicamentos anti-hipertensivos. PMID:29930639

THE INTERMEDIATE LUMINOSITY OPTICAL TRANSIENT SN 2010DA: THE PROGENITOR, ERUPTION, AND AFTERMATH OF A PECULIAR SUPERGIANT HIGH-MASS X-RAY BINARY

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

Villar, V. A.; Berger, E.; Blanchard, P. K.

We present optical spectroscopy, ultraviolet-to-infrared imaging, and X-ray observations of the intermediate luminosity optical transient (ILOT) SN 2010da in NGC 300 ( d = 1.86 Mpc) spanning from −6 to +6 years relative to the time of outburst in 2010. Based on the light-curve and multi-epoch spectral energy distributions of SN 2010da, we conclude that the progenitor of SN 2010da is a ≈10–12 M {sub ⊙} yellow supergiant possibly transitioning into a blue-loop phase. During outburst, SN 2010da had a peak absolute magnitude of M {sub bol} ≲ −10.4 mag, dimmer than other ILOTs and supernova impostors. We detect multi-componentmore » hydrogen Balmer, Paschen, and Ca ii emission lines in our high-resolution spectra, which indicate a dusty and complex circumstellar environment. Since the 2010 eruption, the star has brightened by a factor of ≈5 and remains highly variable in the optical. Furthermore, we detect SN 2010da in archival Swift and Chandra observations as an ultraluminous X-ray source ( L {sub X} ≈ 6 × 10{sup 39} erg s{sup −1}). We additionally attribute He ii 4686 Å and coronal Fe emission lines in addition to a steady X-ray luminosity of ≈10{sup 37} erg s{sup −1} to the presence of a compact companion.« less

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

Tremblay, P.-E.; Bergeron, P.; Gianninas, A., E-mail: tremblay@astro.umontreal.ca, E-mail: bergeron@astro.umontreal.ca, E-mail: gianninas@astro.umontreal.ca

We present an improved spectroscopic and photometric analysis of hydrogen-line DA white dwarfs from the Sloan Digital Sky Survey Data Release 4 (SDSS DR4) based on model atmospheres that include improved Stark broadening profiles with non-ideal gas effects. We also perform a careful visual inspection of all spectroscopic fits with high signal-to-noise ratios (S/Ns > 12) and present improved atmospheric parameters (T{sub eff} and log g) for each white dwarf. Through a comparison of spectroscopic and photometric temperatures, we report the discovery of 35 DA+DB/DC double degenerate candidates and two helium-rich DA stars. We also determine that a cutoff atmore » S/N = 15 optimizes the size and quality of the sample for computing the mean mass of DA white dwarfs, for which we report a value of 0.613 M{sub sun}. We compare our results to previous analyses of the SDSS DR4 and find a good agreement if we account for the shift produced by the improved Stark profiles. Finally, the properties of DA white dwarfs in the SDSS are weighed against those of the Villanova White Dwarf Catalog sample of Gianninas et al. We find systematically lower masses (by about 3% on average), a difference that we trace back to the data reduction procedure of the SDSS. We conclude that a better understanding of these differences will be important to determine the absolute temperature scale and mean mass of DA white dwarfs.« less

Robotic resections in hepatobiliary oncology - initial experience with Xi da Vinci system in India.

PubMed

Chandarana, M; Patkar, S; Tamhankar, A; Garg, S; Bhandare, M; Goel, M

2017-01-01

Minimal invasive surgery has proven its advantages over open surgeries in the perioperative period. Food and Drug Administration approved da Vinci robot in 2000. The latest version, da Vinci Xi system has a mobile tower-based robot with several modifications to improve the functionality, versatility, and operative ease. None of the centers have reported exclusively on hepatobiliary oncology using the da Vinci Xi system. We report our initial experience. To study the feasibility, advantages, and discuss the operative technique of da Vinci Xi system in hepatobiliary oncology. Data were analyzed retrospectively from a prospectively maintained database from June 2015 to October 2016. Twenty-five patients with suspected or proven hepatobiliary malignancies were operated. Total robotic technique using da Vinci Xi system was used. Demographic details and perioperative outcomes were noted. Of the 25 surgeries, 14 patients had a suspected gallbladder malignancy, 11 patients had primary or metastatic liver tumor. Median age was 53 years. The average duration of surgery was 225 min with a median blood loss 150 ml. The median postoperative stay was 4 days. The median nodal yield for radical cholecystectomy was seven. Five patients required conversion. Two of these developed postoperative morbidity. Robotic surgery for hepatobiliary oncology is feasible and can be performed safely in experienced hands. Increasing experience in this field may equal or even prove advantageous over conventional or laparoscopic approach in future. A cautious approach with judicious patient selection is the key to establishing robotic surgery as a standard surgical approach.

Piloted simulation of a ground-based time-control concept for air traffic control

NASA Technical Reports Server (NTRS)

Davis, Thomas J.; Green, Steven M.

1989-01-01

A concept for aiding air traffic controllers in efficiently spacing traffic and meeting scheduled arrival times at a metering fix was developed and tested in a real time simulation. The automation aid, referred to as the ground based 4-D descent advisor (DA), is based on accurate models of aircraft performance and weather conditions. The DA generates suggested clearances, including both top-of-descent-point and speed-profile data, for one or more aircraft in order to achieve specific time or distance separation objectives. The DA algorithm is used by the air traffic controller to resolve conflicts and issue advisories to arrival aircraft. A joint simulation was conducted using a piloted simulator and an advanced concept air traffic control simulation to study the acceptability and accuracy of the DA automation aid from both the pilot's and the air traffic controller's perspectives. The results of the piloted simulation are examined. In the piloted simulation, airline crews executed controller issued descent advisories along standard curved path arrival routes, and were able to achieve an arrival time precision of + or - 20 sec at the metering fix. An analysis of errors generated in turns resulted in further enhancements of the algorithm to improve the predictive accuracy. Evaluations by pilots indicate general support for the concept and provide specific recommendations for improvement.

Treatment with Trehalose Prevents Behavioral and Neurochemical Deficits Produced in an AAV α-Synuclein Rat Model of Parkinson's Disease.

PubMed

He, Qing; Koprich, James B; Wang, Ying; Yu, Wen-bo; Xiao, Bao-guo; Brotchie, Jonathan M; Wang, Jian

2016-05-01

The accumulation of misfolded α-synuclein in dopamine (DA) neurons is believed to be of major importance in the pathogenesis of Parkinson's disease (PD). Animal models of PD, based on viral-vector-mediated over-expression of α-synuclein, have been developed and show evidence of dopaminergic toxicity, providing us a good tool to investigate potential therapies to interfere with α-synuclein-mediated pathology. An efficient disease-modifying therapeutic molecule should be able to interfere with the neurotoxicity of α-synuclein aggregation. Our study highlighted the ability of an autophagy enhancer, trehalose (at concentrations of 5 and 2% in drinking water), to protect against A53T α-synuclein-mediated DA degeneration in an adeno-associated virus serotype 1/2 (AAV1/2)-based rat model of PD. Behavioral tests and neurochemical analysis demonstrated a significant attenuation in α-synuclein-mediated deficits in motor asymmetry and DA neurodegeneration including impaired DA neuronal survival and DA turnover, as well as α-synuclein accumulation and aggregation in the nigrostriatal system by commencing 5 and 2% trehalose at the same time as delivery of AAV. Trehalose (0.5%) was ineffective on the above behavioral and neurochemical deficits. Further investigation showed that trehalose enhanced autophagy in the striatum by increasing formation of LC3-II. This study supports the concept of using trehalose as a novel therapeutic strategy that might prevent/reverse α-synuclein aggregation for the treatment of PD.

Da Vinci-assisted abdominal cerclage.

PubMed

Barmat, Larry; Glaser, Gretchen; Davis, George; Craparo, Frank

2007-11-01

To report the first placement of an abdominal cervicoisthmic cerclage using the da Vinci robot. Case report. Tertiary-care hospital. A 39-year-old female with a history of cervical insufficiency who required a cerclage and was not a candidate for transvaginal cerclage placement. Abdominal cervicoisthmic cerclage placement using the da Vinci robot. Ability to safely and successfully place an abdominal cerclage using the da Vinci robot. Abdominal cerclage was successfully placed using the da Vinci robot. The patient had minimal blood loss and was discharged to home on the same day as surgery. Da Vinci robot-assisted abdominal cerclage placement is an innovative application of robotic surgery and may alter the standard of care for women who require this surgery.

Immunoblot patterns of Taenia asiatica taeniasis.

PubMed

Jeon, Hyeong-Kyu; Eom, Keeseon S

2009-03-01

Differential diagnosis of Taenia asiatica infection from other human taeniases by serology has been tested. An enzyme-linked immunoelectrotransfer blot (EITB) was applied to subjected human sera and tapeworm materials. Thirty-eight proteins reactive to serum IgG were observed between 121 and 10 kDa in adult worms, and more than 22 serum-reactive components between 97 kDa and 21.5 kDa were observed in eggs of T. asiatica. Antigens of adult T. asiatica revealed immunoblot bands between 120 and 21.5 kDa against T. asiatica infected sera. Antigens of adult Taenia saginata revealed 110-100, 66, 58-56, and 46 kDa immunoblot bands against T. asiatica infected sera. Antigens of adult Taenia solium also revealed 99-97, 68-66, and 46 kDa bands against T. asiatica infected sera. The immunoblot band of 21.5 kDa exhibited specificity to T. asiatica.

Specific and common antigens of Clonorchis sinensis and Opisthorchis viverrini (Opisthorchidae, Trematoda)

PubMed Central

Choi, Min-Ho; Ryu, Jin-Sook; Lee, Mejeong; Li, Shunyu; Chung, Byung-Suk; Chai, Jong-Yil; Sithithaworn, Paiboon; Tesana, Smarn

2003-01-01

The antigenic characterizations and serological reactions of human liver flukes, Clonorchis sinensis and Opisthorchis viverrini, were analyzed by immunoblot. The antigenic profiles of the crude extract of Clonorchis contained major proteins of 8, 26-28, 34-37, 43, and 70 kDa, and those of Opisthorchis 34-37, 43, 70, and 100 kDa. Of these, the 8, 26-28 and 34-37 kDa bands of Clonorchis and the 100 kDa of Opisthorchis were major components of each excretory-secretory antigen. The 8 and 26-28 kDa bands were specific to Clonorchis but the 100 kDa of Opisthorchis cross-reacted with the sera of clonorchiasis, and the 34-37, 70 and 100 kDa bands cross-reacted with sera of other helminthiases. The frequency and intensity of the immunoblot reactions were positively correlated with the intensity of the liver fluke infection. PMID:12972729

Immunoblot Patterns of Taenia asiatica Taeniasis

PubMed Central

Jeon, Hyeong-Kyu

2009-01-01

Differential diagnosis of Taenia asiatica infection from other human taeniases by serology has been tested. An enzyme-linked immunoelectrotransfer blot (EITB) was applied to subjected human sera and tapeworm materials. Thirty-eight proteins reactive to serum IgG were observed between 121 and 10 kDa in adult worms, and more than 22 serum-reactive components between 97 kDa and 21.5 kDa were observed in eggs of T. asiatica. Antigens of adult T. asiatica revealed immunoblot bands between 120 and 21.5 kDa against T. asiatica infected sera. Antigens of adult Taenia saginata revealed 110-100, 66, 58-56, and 46 kDa immunoblot bands against T. asiatica infected sera. Antigens of adult Taenia solium also revealed 99-97, 68-66, and 46 kDa bands against T. asiatica infected sera. The immunoblot band of 21.5 kDa exhibited specificity to T. asiatica. PMID:19290097

Dopamine in Drosophila: setting arousal thresholds in a miniature brain

PubMed Central

Van Swinderen, Bruno; Andretic, Rozi

2011-01-01

In mammals, the neurotransmitter dopamine (DA) modulates a variety of behaviours, although DA function is mostly associated with motor control and reward. In insects such as the fruitfly, Drosophila melanogaster, DA also modulates a wide array of behaviours, ranging from sleep and locomotion to courtship and learning. How can a single molecule play so many different roles? Adaptive changes within the DA system, anatomical specificity of action and effects on a variety of behaviours highlight the remarkable versatility of this neurotransmitter. Recent genetic and pharmacological manipulations of DA signalling in Drosophila have launched a surfeit of stories—each arguing for modulation of some aspect of the fly's waking (and sleeping) life. Although these stories often seem distinct and unrelated, there are some unifying themes underlying DA function and arousal states in this insect model. One of the central roles played by DA may involve perceptual suppression, a necessary component of both sleep and selective attention. PMID:21208962

Dopamine Receptors and Parkinson's Disease

PubMed Central

Hisahara, Shin; Shimohama, Shun

2011-01-01

Parkinson's disease (PD) is a progressive extrapyramidal motor disorder. Pathologically, this disease is characterized by the selective dopaminergic (DAergic) neuronal degeneration in the substantia nigra. Correcting the DA deficiency in PD with levodopa (L-dopa) significantly attenuates the motor symptoms; however, its effectiveness often declines, and L-dopa-related adverse effects emerge after long-term treatment. Nowadays, DA receptor agonists are useful medication even regarded as first choice to delay the starting of L-dopa therapy. In advanced stage of PD, they are also used as adjunct therapy together with L-dopa. DA receptor agonists act by stimulation of presynaptic and postsynaptic DA receptors. Despite the usefulness, they could be causative drugs for valvulopathy and nonmotor complication such as DA dysregulation syndrome (DDS). In this paper, physiological characteristics of DA receptor familyare discussed. We also discuss the validity, benefits, and specific adverse effects of pharmaceutical DA receptor agonist. PMID:25954517

Capstone: A Geometry-Centric Platform to Enable Physics-Based Simulation and Design of Systems

DTIC Science & Technology

2015-10-05

foundation for the air-vehicle early design tool DaVinci being developed by CREATETM-AV project to enable development of associative models of air...CREATETM-AV solvers Kestrel [11] and Helios [16,17]. Furthermore, it is the foundation for the CREATETM-AV’s DaVinci [9] tool that provides a... Tools and Environments (CREATETM) program [6] aimed at developing a suite of high- performance physics-based computational tools addressing the needs

Photoacoustic-based approach to surgical guidance performed with and without a da Vinci robot

NASA Astrophysics Data System (ADS)

Gandhi, Neeraj; Allard, Margaret; Kim, Sungmin; Kazanzides, Peter; Lediju Bell, Muyinatu A.

2017-12-01

Death and paralysis are significant risks of modern surgeries, caused by injury to blood vessels and nerves hidden by bone and other tissue. We propose an approach to surgical guidance that relies on photoacoustic (PA) imaging to determine the separation between these critical anatomical features and to assess the extent of safety zones during surgical procedures. Images were acquired as an optical fiber was swept across vessel-mimicking targets, in the absence and presence of teleoperation with a research da Vinci Surgical System. Vessel separation distances were measured directly from PA images. Vessel positions were additionally recorded based on the fiber position (calculated from the da Vinci robot kinematics) that corresponded to an observed PA signal, and these recordings were used to indirectly measure vessel separation distances. Amplitude- and coherence-based beamforming were used to estimate vessel separations, resulting in 0.52- to 0.56-mm mean absolute errors, 0.66- to 0.71-mm root-mean-square errors, and 65% to 68% more accuracy compared to fiber position measurements obtained through the da Vinci robot kinematics. Similar accuracy was achieved in the presence of up to 4.5-mm-thick ex vivo tissue. Results indicate that PA image-based measurements of the separation among anatomical landmarks could be a viable method for real-time path planning in multiple interventional PA applications.

Dopamine modulates hemocyte phagocytosis via a D1-like receptor in the rice stem borer, Chilo suppressalis

USDA-ARS?s Scientific Manuscript database

Dopamine (DA) is a signal moiety bridging the nervous and immune systems. DA dysregulation is linked to serious human diseases, including addiction, schizophrenia, and Parkinson's disease. However, DA actions in the immune system remain incompletely understood. In this study, we found that DA modula...

40 CFR 60.42Da - Standard for particulate matter (PM).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Standard for particulate matter (PM). 60.42Da Section 60.42Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR....42Da Standard for particulate matter (PM). (a) On and after the date on which the initial performance...

40 CFR 60.42Da - Standard for particulate matter (PM).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 6 2011-07-01 2011-07-01 false Standard for particulate matter (PM). 60.42Da Section 60.42Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR....42Da Standard for particulate matter (PM). (a) On and after the date on which the initial performance...

32 CFR 635.13 - Amendment of records.

Code of Federal Regulations, 2010 CFR

2010-07-01

... delegable. If the decision is made to amend an MPR, a supplemental DA Form 3975 will be prepared. The supplemental DA Form 3975 will change information on the original DA Form 3975 and will be mailed to the... file the supplemental DA Form 3975 with the original MPR and notify the requestor of the amendment of...

32 CFR 536.119 - Scope for maritime claims.

Code of Federal Regulations, 2010 CFR

2010-07-01

... vessel of, or in the service of, the Department of the Army (DA) or by other property under the jurisdiction of the DA. (b) Compensation for towage and salvage service, including contract salvage, rendered to a vessel of, or in the service of, the DA or other property under the jurisdiction of the DA. (c...

76 FR 31457 - Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes AGENCY: Federal Aviation... reportedly found on DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard maintenance... DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard maintenance. Depending on...

76 FR 14346 - Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

... Industries GmbH Model DA 42 Airplanes AGENCY: Federal Aviation Administration (FAA), Department of... been reportedly found on DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard... condition for the specified products. The MCAI states: Cracks have been reportedly found on DA 42 Main...

Endogenous dopamine (DA) modulates (3H)spiperone binding in vivo in rat brain

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

Bischoff, S.; Krauss, J.; Grunenwald, C.

1991-01-01

(3H)spiperone (SPI) binding in vivo, biochemical parameters and behavior were measured after modulating DA levels by various drug treatments. DA releasers and uptake inhibitors increased SPI binding in rat striatum. In other brain areas, the effects were variable, but only the pituitary remained unaffected. Surprisingly, nomifensine decreased SPI binding in frontal cortex. The effects of these drugs were monitored by measuring DA, serotonin (5-HT) and their metabolites in the same rats. The increased SPI binding in striatum was parallel to the locomotor stimulation with the following rank order: amfonelic acid greater than nomifensine greater than D-amphetamine greater than or equalmore » to methylphenidate greater than amineptine greater than bupropion. Decreasing DA levels with reserpine or alpha-methyl-para-tyrosine reduced SPI binding by 45% in striatum only when both drugs were combined. In contrast, reserpine enhanced SPI binding in pituitary. Thus, the amount of releasable DA seems to modulate SPI binding characteristics. It is suggested that in vivo, DA receptors are submitted to dynamic regulation in response to changes in intrasynaptic concentrations of DA.« less

Discourse analysis: A useful methodology for health-care system researches

PubMed Central

Yazdannik, Ahmadreza; Yousefy, Alireza; Mohammadi, Sepideh

2017-01-01

Discourse analysis (DA) is an interdisciplinary field of inquiry and becoming an increasingly popular research strategy for researchers in various disciplines which has been little employed by health-care researchers. The methodology involves a focus on the sociocultural and political context in which text and talk occur. DA adds a linguistic approach to an understanding of the relationship between language and ideology, exploring the way in which theories of reality and relations of power are encoded in such aspects as the syntax, style, and rhetorical devices used in texts. DA is a useful and productive qualitative methodology but has been underutilized within health-care system research. Without a clear understanding of discourse theory and DA it is difficult to comprehend important research findings and impossible to use DA as a research strategy. To redress this deficiency, in this article, represents an introduction to concepts of discourse and DA, DA history, Philosophical background, DA types and analysis strategy. Finally, we discuss how affect to the ideological dimension of such phenomena discourse in health-care system, health beliefs and intra-disciplinary relationship in health-care system. PMID:29296612

Discourse analysis: A useful methodology for health-care system researches.

PubMed

Yazdannik, Ahmadreza; Yousefy, Alireza; Mohammadi, Sepideh

2017-01-01

Discourse analysis (DA) is an interdisciplinary field of inquiry and becoming an increasingly popular research strategy for researchers in various disciplines which has been little employed by health-care researchers. The methodology involves a focus on the sociocultural and political context in which text and talk occur. DA adds a linguistic approach to an understanding of the relationship between language and ideology, exploring the way in which theories of reality and relations of power are encoded in such aspects as the syntax, style, and rhetorical devices used in texts. DA is a useful and productive qualitative methodology but has been underutilized within health-care system research. Without a clear understanding of discourse theory and DA it is difficult to comprehend important research findings and impossible to use DA as a research strategy. To redress this deficiency, in this article, represents an introduction to concepts of discourse and DA, DA history, Philosophical background, DA types and analysis strategy. Finally, we discuss how affect to the ideological dimension of such phenomena discourse in health-care system, health beliefs and intra-disciplinary relationship in health-care system.

Study of Hydroquinone Mediated Cytotoxicity and Hypopigmentation Effects from UVB-Irradiated Arbutin and DeoxyArbutin

PubMed Central

Chang, Nai-Fang; Chen, Yi-Shyan; Lin, Ying-Ju; Tai, Ting-Hsuan; Chen, An-Ni; Huang, Chen-Hsuan; Lin, Chih-Chien

2017-01-01

Arbutin (Arb) and deoxyArbutin (dA) are both effective hypopigmentation agents. However, they are glucoside derivatives of hydroquinone (HQ), which may be decayed into HQ under higher energy environments. Therefore, safety and toxicity are very important issues when considering the usage of these compounds. However, no study has verified the properties of Ultra-Violet B (UVB)-irradiated Arb and dA. In this work, we investigated the cytotoxicity and hypopigmentation effects of UVB-irradiated Arb and dA in Detroit 551 human fibroblast cells and B16-F10 mouse melanoma cells. The results showed that UVB-irradiated Arb and dA have strong cytotoxicity for the fibroblast cells, especially for dA, the caspase-3 is also activated by the treatment of UVB-irradiated dA in Detroit 551 cells. The results correlated with the produced HQ. In addition, UVB-irradiated Arb and dA suppressed the production of melanin in melanoma cells; this is due to the release of HQ that compensates for the UVB triggered Arb and dA decomposition. PMID:28467382

Study of Hydroquinone Mediated Cytotoxicity and Hypopigmentation Effects from UVB-Irradiated Arbutin and DeoxyArbutin.

PubMed

Chang, Nai-Fang; Chen, Yi-Shyan; Lin, Ying-Ju; Tai, Ting-Hsuan; Chen, An-Ni; Huang, Chen-Hsuan; Lin, Chih-Chien

2017-05-03

Arbutin (Arb) and deoxyArbutin (dA) are both effective hypopigmentation agents. However, they are glucoside derivatives of hydroquinone (HQ), which may be decayed into HQ under higher energy environments. Therefore, safety and toxicity are very important issues when considering the usage of these compounds. However, no study has verified the properties of Ultra-Violet B (UVB)-irradiated Arb and dA. In this work, we investigated the cytotoxicity and hypopigmentation effects of UVB-irradiated Arb and dA in Detroit 551 human fibroblast cells and B16-F10 mouse melanoma cells. The results showed that UVB-irradiated Arb and dA have strong cytotoxicity for the fibroblast cells, especially for dA, the caspase-3 is also activated by the treatment of UVB-irradiated dA in Detroit 551 cells. The results correlated with the produced HQ. In addition, UVB-irradiated Arb and dA suppressed the production of melanin in melanoma cells; this is due to the release of HQ that compensates for the UVB triggered Arb and dA decomposition.

Soybean P34 Probable Thiol Protease Probably Has Proteolytic Activity on Oleosins.

PubMed

Zhao, Luping; Kong, Xiangzhen; Zhang, Caimeng; Hua, Yufei; Chen, Yeming

2017-07-19

P34 probable thiol protease (P34) and Gly m Bd 30K (30K) show high relationship with the protease of 24 kDa oleosin of soybean oil bodies. In this study, 9 day germinated soybean was used to separate bioprocessed P34 (P32) from bioprocessed 30K (28K). Interestingly, P32 existed as dimer, whereas 28K existed as monomer; a P32-rich sample had proteolytic activity and high cleavage site specificity (Lys-Thr of 24 kDa oleosin), whereas a 28K-rich sample showed low proteolytic activity; the P32-rich sample contained one thiol protease. After mixing with purified oil bodies, all P32 dimers were dissociated and bound to 24 kDa oleosins to form P32-24 kDa oleosin complexes. By incubation, 24 kDa oleosin was preferentially hydrolyzed, and two hydrolyzed products (HPs; 17 and 7 kDa) were confirmed. After most of 24 kDa oleosin was hydrolyzed, some P32 existed as dimer, and the other as P32-17 kDa HP. It was suggested that P32 was the protease.

The butter flavorant, diacetyl, exacerbates β-amyloid cytotoxicity.

PubMed

More, Swati S; Vartak, Ashish P; Vince, Robert

2012-10-15

Diacetyl (DA), an ubiquitous butter-flavoring agent, was found to influence several aspects of amyloid-β (Aβ) aggregation--one of the two primary pathologies associated with Alzheimer's disease. Thioflavin T fluorescence and circular dichroism spectroscopic measurements revealed that DA accelerates Aβ¹⁻⁴² aggregation into soluble and ultimately insoluble β-pleated sheet structures. DA was found to covalently bind to Arg⁵ of Aβ¹⁻⁴² through proteolytic digestion-mass spectrometric experiments. These biophysical and chemical effects translated into the potentiation of Aβ¹⁻⁴² cytotoxicity by DA toward SH-SY5Y cells in culture. DA easily traversed through a MDR1-MDCK cell monolayer, an in vitro model of the blood-brain barrier. Additionally, DA was found not only to be resistant to but also inhibitory toward glyoxalase I, the primary initiator of detoxification of amyloid-promoting reactive dicarbonyl species that are generated naturally in large amounts by neuronal tissue. In light of the chronic exposure of industry workers to DA, this study raises the troubling possibility of long-term neurological toxicity mediated by DA.

Fluorescent light induces neurodegeneration in the rodent nigrostriatal system but near infrared LED light does not.

PubMed

Romeo, Stefania; Vitale, Flora; Viaggi, Cristina; di Marco, Stefano; Aloisi, Gabriella; Fasciani, Irene; Pardini, Carla; Pietrantoni, Ilaria; Di Paolo, Mattia; Riccitelli, Serena; Maccarone, Rita; Mattei, Claudia; Capannolo, Marta; Rossi, Mario; Capozzo, Annamaria; Corsini, Giovanni U; Scarnati, Eugenio; Lozzi, Luca; Vaglini, Francesca; Maggio, Roberto

2017-05-01

We investigated the effects of continuous artificial light exposure on the mouse substantia nigra (SN). A three month exposure of C57Bl/6J mice to white fluorescent light induced a 30% reduction in dopamine (DA) neurons in SN compared to controls, accompanied by a decrease of DA and its metabolites in the striatum. After six months of exposure, neurodegeneration progressed slightly, but the level of DA returned to the basal level, while the metabolites increased with respect to the control. Three month exposure to near infrared LED light (∼710nm) did not alter DA neurons in SN, nor did it decrease DA and its metabolites in the striatum. Furthermore mesencephalic cell viability, as tested by [ 3 H]DA uptake, did not change. Finally, we observed that 710nm LED light, locally conveyed in the rat SN, could modulate the firing activity of extracellular-recorded DA neurons. These data suggest that light can be detrimental or beneficial to DA neurons in SN, depending on the source and wavelength. Copyright © 2017 Elsevier B.V. All rights reserved.

PanDaTox: A tool for accelerated metabolic engineering

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

Amitai, Gil; Sorek, Rotem

2012-07-18

Metabolic engineering is often facilitated by cloning of genes encoding enzymes from various heterologous organisms into E. coli. Such engineering efforts are frequently hampered by foreign genes that are toxic to the E. coli host. We have developed PanDaTox (www.weizmann.ac.il/pandatox), a web-based resource that provides experimental toxicity information for more than 1.5 million genes from hundreds of different microbial genomes. The toxicity predictions, which were extensively experimentally verified, are based on serial cloning of genes into E. coli as part of the Sanger whole genome shotgun sequencing process. PanDaTox can accelerate metabolic engineering projects by allowing researchers to exclude toxicmore » genes from the engineering plan and verify the clonability of selected genes before the actual metabolic engineering experiments are conducted.« less

Different protein profile in amniotic fluid with nervous system malformations by surface-enhanced laser desorption-ionization/time-of-flight mass spectrometry (SELDI-TOF-MS) technology.

PubMed

Ma, Zhe; Liu, Cun; Deng, Biping; Dong, Shaogang; Tao, Guowei; Zhan, Xinfeng; Wang, Chuner; Liu, Shaoping; Qu, Xun

2010-12-01

To detect the distinct proteins in amniotic fluid (AF) between nervous system malformations fetuses and normal fetuses. Surface-enhanced laser desorption-ionization/time-of-flight mass spectrometry was used to characterize AF peptides in AF between nervous system malformations fetuses and normal fetuses. WCX2 protein chips were used to characterize AF peptides in AF. Protein chips were examined in a PBSIIC protein reader, the protein profiling was collected by ProteinChip software version 3.1 (Ciphergen Biosystems, Fremont, CA, USA) and analyzed by Biomarker Wizard software (Ciphergen Biosystems). Nine distinct proteins were identified in AF between nervous system malformations fetuses and normal fetuses. Compared with the control group, three proteins with m/z 4967.5 Da, 5258.0 Da, and 11,717.0 Da were down-regulated, and six proteins with m/z 2540.4 Da, 3107.1 Da, 3396.8 Da, 4590.965 Da, 5589.2 Da and 6429.4 Da up-regulated in nervous system malformations fetuses. The results suggest that there are distinct proteins in protein profiling of AF between nervous system malformations fetuses and normal fetuses. © 2010 The Authors. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology.

Dopamine Receptors and Neurodegeneration

PubMed Central

Rangel-Barajas, Claudia; Coronel, Israel; Florán, Benjamín

2015-01-01

Dopamine (DA) is one of the major neurotransmitters and participates in a number of functions such as motor coordination, emotions, memory, reward mechanism, neuroendocrine regulation etc. DA exerts its effects through five DA receptors that are subdivided in 2 families: D1-like DA receptors (D1 and D5) and the D2-like (D2, D3 and D4). All DA receptors are widely expressed in the central nervous system (CNS) and play an important role in not only in physiological conditions but also pathological scenarios. Abnormalities in the DAergic system and its receptors in the basal ganglia structures are the basis Parkinson’s disease (PD), however DA also participates in other neurodegenerative disorders such as Huntington disease (HD) and multiple sclerosis (MS). Under pathological conditions reorganization of DAergic system has been observed and most of the times, those changes occur as a mechanism of compensation, but in some cases contributes to worsening the alterations. Here we review the changes that occur on DA transmission and DA receptors (DARs) at both levels expression and signals transduction pathways as a result of neurotoxicity, inflammation and in neurodegenerative processes. The better understanding of the role of DA receptors in neuropathological conditions is crucial for development of novel therapeutic approaches to treat alterations related to neurodegenerative diseases. PMID:26425390

Amphetamine Augments Action Potential-Dependent Dopaminergic Signaling in the Striatum in Vivo

PubMed Central

Ramsson, Eric S.; Covey, Daniel P.; Daberkow, David P.; Litherland, Melissa T.; Juliano, Steven A.; Garris, Paul A.

2011-01-01

Amphetamine (AMPH) is thought to disrupt normal patterns of action potential-dependent dopaminergic signaling by depleting dopamine (DA) vesicular stores and promoting non-exocytotic DA efflux. Voltammetry in brain slices concurrently demonstrates these key drug effects, along with competitive inhibition of neuronal DA uptake. Here we perform comparable kinetic and voltammetric analyses in vivo to determine whether AMPH acts qualitatively and quantitatively similar in the intact brain. Fast-scan cyclic voltammetry measured extracellular DA in dorsal and ventral striata of urethane-anesthetized rats. Electrically evoked recordings were analyzed to determine Km and Vmax for DA uptake and vesicular DA release, while background voltammetric current indexed basal DA concentration. AMPH (0.5, 3, and 10 mg/kg i.p.) robustly increased evoked DA responses in both striatal subregions. The predominant contributor to these elevated levels was competitive uptake inhibition, as exocytotic release was unchanged in the ventral striatum and only modestly decreased in the dorsal striatum. Increases in basal DA levels were not detected. These results are consistent with AMPH augmenting action potential-dependent dopaminergic signaling in vivo across a wide, behaviorally relevant dose range. Future work should be directed at possible causes for the distinct in vitro and in vivo pharmacology of AMPH. PMID:21443523

Purification and sequence analysis of two rat tissue inhibitors of metalloproteinases

NASA Technical Reports Server (NTRS)

Roswit, W. T.; McCourt, D. W.; Partridge, N. C.; Jeffrey, J. J.

1992-01-01

Two protein inhibitors of metalloproteinases (TIMP) were isolated from medium conditioned by the clonal rat osteosarcoma line UMR 106-01. Initial purification of both a 30-kDa inhibitor and a 20-kDa inhibitor was accomplished using heparin-Sepharose chromatography with dextran sulfate elution followed by DEAE-Sepharose and CM-Sepharose chromatography. Purification of the 20-kDa inhibitor to homogeneity was completed with reverse-phase high-performance liquid chromatography. The 20-kDa inhibitor was identified as rat TIMP-2. The 30-kDa inhibitor, although not purified to homogeneity, was identified as rat TIMP-1. Amino terminal amino acid sequence analysis of the 30-kDa inhibitor demonstrated 86% identity to human TIMP-1 for the first 22 amino acids while the sequence of the 20-kDa inhibitor was identical to that of human TIMP-2 for the first 22 residues. Treatment with peptide:N-glycosidase F indicated that the 30-kDa rat inhibitor is glycosylated while the 20-kDa inhibitor is apparently unglycosylated. Inhibition of both rat and human interstitial collagenase by rat TIMP-2 was stoichiometric, with a 1:1 molar ratio required for complete inhibition. Exposure of UMR 106-01 cells to 10(-7) M parathyroid hormone resulted in approximately a 40% increase in total inhibitor production over basal levels.

ATLAS WORLD-cloud and networking in PanDA

NASA Astrophysics Data System (ADS)

Barreiro Megino, F.; De, K.; Di Girolamo, A.; Maeno, T.; Walker, R.; ATLAS Collaboration

2017-10-01

The ATLAS computing model was originally designed as static clouds (usually national or geographical groupings of sites) around the Tier 1 centres, which confined tasks and most of the data traffic. Since those early days, the sites’ network bandwidth has increased at 0(1000) and the difference in functionalities between Tier 1s and Tier 2s has reduced. After years of manual, intermediate solutions, we have now ramped up to full usage of World-cloud, the latest step in the PanDA Workload Management System to increase resource utilization on the ATLAS Grid, for all workflows (MC production, data (re)processing, etc.). We have based the development on two new site concepts. Nuclei sites are the Tier 1s and large Tier 2s, where tasks will be assigned and the output aggregated, and satellites are the sites that will execute the jobs and send the output to their nucleus. PanDA dynamically pairs nuclei and satellite sites for each task based on the input data availability, capability matching, site load and network connectivity. This contribution will introduce the conceptual changes for World-cloud, the development necessary in PanDA, an insight into the network model and the first half-year of operational experience.

Visible light photoelectrochemical sensor for ultrasensitive determination of dopamine based on synergistic effect of graphene quantum dots and TiO2 nanoparticles.

PubMed

Yan, Yuting; Liu, Qian; Du, Xiaojiao; Qian, Jing; Mao, Hanping; Wang, Kun

2015-01-01

We have demonstrated a facile approach for fabricating graphene quantum dots-TiO2 (GQDs-TiO2) nanocomposites by a simple physical adsorption method. Compared with pure GQDs and TiO2 nanoparticles (NPs), the as-prepared GQDs-TiO2 nanocomposites showed enhanced photoelectrochemical (PEC) signal under visible-light irradiation. The photocurrent of GQDs-TiO2/GCE was nearly 30-fold and 12-fold enhancement than that of GQDs/GCE and TiO2/GCE, respectively, which was attributed to the synergistic amplification between TiO2 NPs and GQDs. More interestingly, the photocurrent of GQDs-TiO2 nanocomposites was selectively sensitized by dopamine (DA), and enhanced with the increasing of DA concentration. Further, a new PEC methodology for ultrasensitive determination of DA was developed, which showed linearly enhanced photocurrent by increasing the DA concentration from 0.02 to 105 μM with a detection limit of 6.7 nM (S/N=3) under optimized conditions. This strategy opens up a new avenue for the application of GQDs-based nanocomposites in the field of PEC sensing and monitoring. Copyright © 2014 Elsevier B.V. All rights reserved.

The DaNa2.0 Knowledge Base Nanomaterials—An Important Measure Accompanying Nanomaterials Development

PubMed Central

Bohmer, Nils; Marquardt, Clarissa; Nau, Katja; Steinbach, Christoph

2018-01-01

Nanotechnology is closely related to the tailored manufacturing of nanomaterials for a huge variety of applications. However, such applications with newly developed materials are also a reason for concern. The DaNa2.0 project provides information and support for these issues on the web in condensed and easy-to-understand wording. Thus, a key challenge in the field of advanced materials safety research is access to correct and reliable studies and validated results. For nanomaterials, there is currently a continuously increasing amount of publications on toxicological issues, but criteria to evaluate the quality of these studies are necessary to use them e.g., for regulatory purposes. DaNa2.0 discusses scientific results regarding 26 nanomaterials based on actual literature that has been selected after careful evaluation following a literature criteria checklist. This checklist is publicly available, along with a selection of standardized operating protocols (SOPs) established by different projects. The spectrum of information is rounded off by further articles concerning basics or crosscutting topics in nanosafety research. This article is intended to give an overview on DaNa2.0 activities to support reliable toxicity testing and science communication alike. PMID:29596351

Magnetic field effect in organic light emitting diodes based on donor-acceptor exciplexes showing thermally activated delayed fluorescence

NASA Astrophysics Data System (ADS)

Baniya, S.; Pang, Z.; Sun, D.; Basel, T.; Zhai, Y.; Kwon, O.; Choi, H.; Vardeny, Z. V.

2016-09-01

A new type of organic light-emitting diode (OLED) has emerged that shows enhanced operational stability and large internal quantum efficiency approaching 100%, which is based on exciplexes in donor-acceptor (D-A) blends having thermally activated delayed fluorescence (TADF) when doped with fluorescent emitters. We have investigated magnetoelectroluminescence (MEL) and magneto-conductivity in such TADF-based OLEDs, as well as magnetophotoluminescence (MPL) in thin films based on the OLEDs active layers, with various fluorescence emitters. We found that both MEL and MPL responses are thermally activated with substantially lower activation energy compared to that in the pristine undoped D-A exciplex host blend. In addition, both MPL and MEL steeply decrease with the emitters' concentration. This indicates the existence of a loss mechanism, whereby the triplet charge-transfer state in the D-A exciplex host blend may directly decay to the lowest, non-emissive triplet state of the additive fluorescent emitter molecules.

Characteristics of Dynamic Magnetic Resonance Image Enhancement in Prolactinomas Resistant to Dopamine Agonist Therapy

PubMed Central

Guo, Qinghua; Erickson, Bradley J.; Chang, Alice Y.; Erickson, Dana

2015-01-01

Objective To determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. Methods We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, Minnesota). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naïve groups, and between the first and follow-up dMRIs. Results We identified 49 patients with prolactinomas, with 6 (12.2%) that showed DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group vs the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P=.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P=.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% CI, 1.07-3.27; P=.02). Conclusions dMRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas. PMID:25551412

Characteristics of dynamic magnetic resonance image enhancement in prolactinomas resistant to dopamine agonist therapy.

PubMed

Guo, Qinghua; Erickson, Bradley J; Chang, Alice Y; Erickson, Dana

2015-03-01

The objective of this study was to determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, MN). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naive groups, and between the first and follow-up dMRIs. We identified 49 patients with prolactinomas, with 6 (12.2%) showing DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group versus the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P = 0.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P = 0.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% confidence interval, 1.07-3.27; P = 0.02). Dynamic MRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas.

A monoclonal antibody that distinguishes latent and active forms of the proteasome (multicatalytic proteinase complex)

NASA Technical Reports Server (NTRS)

Weitman, D.; Etlinger, J. D.

1992-01-01

Monoclonal antibodies (mAbs) were generated to proteasome purified from human erythrocytes. Five of six proteasome-specific mAbs reacted with three subunits in the molecular mass range of 25-28 kDa, indicating a common epitope. The other mAb (AP5C10) exhibited a more restricted reactivity, recognizing a 32-kDa subunit of the proteasome purified in its latent state. However, when the proteasome is isolated in its active state, AP5C10 reacts with a 28-kDa subunit, evidence for processing of the proteasome subunits during purification. Purified proteasome preparations which exhibited partial latency have both AP5C10 reactive subunits. Although the 32-kDa subunit appears required for latency, loss of this component and generation of the 28-kDa component are not obligatory for activation. The 32- and 28-kDa subunits can each be further resolved into three components by isoelectric focusing. The apparent loss of 4 kDa during the conversion of the 32- to 28-kDa subunit is accompanied by a shift to a more basic pI for each polypeptide. Western blots of the early steps of proteasome purification reveal an AP5C10-reactive protein at 41 kDa. This protein was separated from proteasomes by sizing chromatography and may represent a pool of precursor subunits. Since the 32-kDa subunit appears necessary for latency, it is speculated to play a regulatory role in ATP-dependent proteolytic activity.

Electrochemical Detection of Dopamine via Assisted Ion Transfer at Nanopipet Electrode Using Cyclic Voltammetry.

PubMed

Colombo, Michelle L; McNeil, Swami; Iwai, Nicholas; Chang, Albert; Shen, Mei

2016-01-01

We present here the detection of dopamine (DA) at nanopipet electrodes with radii of hundreds of nanometers ranging from 160 nm to 480 nm. Dibenzo-18-crown-6 (DB18C6) was employed as an ionophore to facilitate DA transfer, resulting in a half-wave transfer potential, E 1/2, DA , of -0.322 (±0.020) V vs. E 1/2, TBA . Well-defined steady-state sigmoidal cyclic voltammograms were observed for the transfer of DA. High resolution scanning electron microscopy was used to measure the size and taper angle of the nanopipet electrodes. The detection is linear with concentration of DA ranging from 0.25 mM to 2 mM; calculated diffusion coefficient at nanopipet electrodes with above mentioned sizes is 4.87 (±0.28) × 10 -10 m 2 /s. The effect of the common interferent ascorbic acid on DA detection with nanopipet electrodes was evaluated, where DA detection still shows linear behavior with well-defined sigmoidal CVs with E 1/2, DA being -0.328 (±0.029) V vs. E 1/2, TBA . The diffusion coefficient for DA transfer in MgCl 2 with the presence of 2 mM AA was measured to be 1.93 (±0.59) × 10 -10 m 2 /s on nanoelectrodes with radii from 161 nm to 263 nm, but the physiological concentration of 0.1 mM AA had no effect on DA's diffusion coefficient.

Bursting as a source of non-linear determinism in the firing patterns of nigral dopamine neurons

PubMed Central

Jeong, Jaeseung; Shi, Wei-Xing; Hoffman, Ralph; Oh, Jihoon; Gore, John C.; Bunney, Benjamin S.; Peterson, Bradley S.

2012-01-01

Nigral dopamine (DA) neurons in vivo exhibit complex firing patterns consisting of tonic single-spikes and phasic bursts that encode information for certain types of reward-related learning and behavior. Non-linear dynamical analysis has previously demonstrated the presence of a non-linear deterministic structure in complex firing patterns of DA neurons, yet the origin of this non-linear determinism remains unknown. In this study, we hypothesized that bursting activity is the primary source of non-linear determinism in the firing patterns of DA neurons. To test this hypothesis, we investigated the dimension complexity of inter-spike interval data recorded in vivo from bursting and non-bursting DA neurons in the chloral hydrate-anesthetized rat substantia nigra. We found that bursting DA neurons exhibited non-linear determinism in their firing patterns, whereas non-bursting DA neurons showed truly stochastic firing patterns. Determinism was also detected in the isolated burst and inter-burst interval data extracted from firing patterns of bursting neurons. Moreover, less bursting DA neurons in halothane-anesthetized rats exhibited higher dimensional spiking dynamics than do more bursting DA neurons in chloral hydrate-anesthetized rats. These results strongly indicate that bursting activity is the main source of low-dimensional, non-linear determinism in the firing patterns of DA neurons. This finding furthermore suggests that bursts are the likely carriers of meaningful information in the firing activities of DA neurons. PMID:22831464

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica

PubMed Central

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 (DaCBF4), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4-overexpressing transgenic rice plant (Ubi:DaCBF4) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice. PMID:29774046

Influence of Culture Conditions on Expression of the 40-Kilodalton Porin Protein of Vibrio anguillarum Serotype O2

PubMed Central

Davey, Michelle L.; Hancock, Robert E. W.; Mutharia, Lucy M.

1998-01-01

Vibrio anguillarum serotype O2 strains express a 40-kDa outer membrane porin protein. Immunoblot analysis revealed that antigenic determinants of the V. anguillarum O2 40-kDa porin were conserved within bacterial species of the genus Vibrio. The relative amounts of the V. anguillarum O2 40-kDa porin were enhanced by growth of V. anguillarum O2 in CM9 medium containing 5 to 10% sucrose or 0.1 to 0.5 M NaCl. In contrast, the levels of the porin were significantly reduced when cells were grown at 37°C, and a novel 60-kDa protein was also observed. However, the osmolarity or ionic concentration of the growth medium did not influence expression of the 60-kDa protein. Growth in medium containing greater than 0.6 mM EDTA reduced production of the V. anguillarum O2 40-kDa porin and enhanced levels of a novel 19-kDa protein. Thus, expression of the V. anguillarum O2 40-kDa porin was osmoregulated and possibly coregulated by temperature. The N-terminal amino acid sequence of the V. anguillarum O2 40-kDa protein and the effect of environmental factors on the cellular levels of the porin suggested that the V. anguillarum O2 40-kDa porin was functionally similar to the OmpC porin of Escherichia coli. However, pore conductance assays revealed that the V. anguillarum O2 40-kDa porin was a general diffusion porin with a pore size in the range of that of the OmpF porin of E. coli. PMID:9435071

Norepinephrine Activates Dopamine D4 Receptors in the Rat Lateral Habenula

PubMed Central

Root, David H.; Hoffman, Alexander F.; Good, Cameron H.; Zhang, Shiliang; Gigante, Eduardo

2015-01-01

The lateral habenula (LHb) is involved in reward and aversion and is reciprocally connected with dopamine (DA)-containing brain regions, including the ventral tegmental area (VTA). We used a multidisciplinary approach to examine the properties of DA afferents to the LHb in the rat. We find that >90% of VTA tyrosine hydroxylase (TH) neurons projecting to the LHb lack vesicular monoamine transporter 2 (VMAT2) mRNA, and there is little coexpression of TH and VMAT2 protein in this mesohabenular pathway. Consistent with this, electrical stimulation of LHb did not evoke DA-like signals, assessed with fast-scan cyclic voltammetry. However, electrophysiological currents that were inhibited by L741,742, a DA-D4-receptor antagonist, were observed in LHb neurons when DA uptake or degradation was blocked. To prevent DA activation of D4 receptors, we repeated this experiment in LHb slices from DA-depleted rats. However, this did not disrupt D4 receptor activation initiated by the dopamine transporter inhibitor, GBR12935. As the LHb is also targeted by noradrenergic afferents, we examined whether GBR12935 activation of DA-D4 receptors occurred in slices depleted of norepinephrine (NE). Unlike DA, NE depletion prevented the activation of DA-D4 receptors. Moreover, direct application of NE elicited currents in LHb neurons that were blocked by L741,742, and GBR12935 was found to be a more effective blocker of NE uptake than the NE-selective transport inhibitor nisoxetine. These findings demonstrate that NE is released in the rat LHb under basal conditions and that it activates DA-D4 receptors. Therefore, NE may be an important regulator of LHb function. PMID:25716845

Redox changes accompanying storage protein mobilization in moist chilled and warm incubated walnut kernels prior to germination.

PubMed

Shahmoradi, Zeynab; Tamaskani, Fatemeh; Sadeghipour, Hamid Reza; Abdolzadeh, Ahmad

2013-01-01

Alterations in the redox state of storage proteins and the associated proteolytic processes were investigated in moist-chilled and warm-incubated walnut (Juglans regia L.) kernels prior to germination. The kernel total protein labeling with a thiol-specific fluorochrome i.e. monobromobimane (mBBr) revealed more reduction of 29-32 kDa putative glutelins, while in the soluble proteins, both putative glutelins and 41, 55 and 58 kDa globulins contained reduced disulfide bonds during mobilization. Thus, the in vivo more reduced disulfide bonds of storage proteins corresponds to greater solubility. After the in vitro reduction of walnut kernel proteins pre-treated by N-ethyl maleimide (NEM) with dithioerythrethiol (DTT) and bacterial thioredoxin, the 58 kDa putative globulin and a 6 kDa putative albumin were identified as disulfide proteins. Thioredoxin stimulated the reduction of the H(2)O(2)-oxidized 6 kDa polypeptide, but not the 58 kDa polypeptide by DTT. The solubility of 6 kDa putative albumin, 58 and 19-24 kDa putative globulins and glutelins, respectively, were increased by DTT. The in vitro specific mobilization of the 58 kDa polypeptide that occurred at pH 5.0 by the kernel endogenous protease was sensitive to the serine-protease inhibitor phenylmethylsulfonyl fluoride (PMSF) and stimulated by DTT. The specific degradation of the 58 kDa polypeptide might be achieved through thioredoxin-mediated activation of a serine protease and/or reductive unfolding of its 58 kDa polypeptide substrate. As redox changes in storage proteins occurred equally in both moist chilled and warm incubated walnut kernels, the regulatory functions of thioredoxins in promoting seed germination may be due to other germination related processes. Copyright © 2012 Elsevier GmbH. All rights reserved.

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate

PubMed Central

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-01-01

The central extended amygdala (CEA) has been conceptualized as a ‘macrosystem’ that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the ‘limbic-associative’ striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning. PMID:28220796

Chronic treatment of DA-8159, a new phosphodiesterase type V inhibitor, attenuates endothelial dysfunction in stroke-prone spontaneously hypertensive rat.

PubMed

Choi, Seul Min; Kim, Jee Eun; Kang, Kyung Koo

2006-02-09

This study examined the effects of chronic treatment of a new phosphodiesterase type 5 inhibitor, DA-8159, on endothelial dysfunction in stroke-prone spontaneously hypertensive rats (SHR-SP). Six-week-old male SHR-SP were divided into 4 groups; vehicle control, DA-8159 1, 3, and 10 mg/kg/day. During a 32-week experimental period, the animals were administered DA-8159 orally and fed a 4% NaCl-loaded diet. The systolic blood pressure was measured every two weeks throughout the experimental period using the tail-cuff method. At the end of experiments, the vascular function (acetylcholine-induced vasodilation) in the endothelium-intact aortic rings was investigated. In addition, the mortality, the left ventricular hypertrophy index, the plasma parameters and the incidence of a cerebral infarction were assessed. In the DA-8159 treated-rats, the vascular reactivity improved significantly in a dose-dependent manner. Although DA-8159 did not alter the elevation of the systolic blood pressure directly, the 3 and 10 mg/kg/day DA-8159 treatment delayed the early death caused by stroke. DA-8159 significantly reduced the left ventricular heart weight/body weight ratio compared with the vehicle control group. Furthermore, the DA-8159 treatment significantly increased the plasma nitric oxide, cGMP, and the total antioxidative status. The DA-8159 treatment also reduced the occurrence of stroke-associated cerebral damage. These results indicate that DA-8159 can ameliorate an endothelial dysfunction-related vascular injury. Therefore, pharmacological intervention aimed at attenuating an endothelial dysfunction is important and might be useful in both preventing and treating endothelial dysfunction-related complications.

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica.

PubMed

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 ( DaCBF4 ), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4 -overexpressing transgenic rice plant ( Ubi:DaCBF4 ) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice.

Chemopreventive effects of Korean Angelica vs. its major pyranocoumarins on two lineages of transgenic adenocarcinoma of mouse prostate carcinogenesis

PubMed Central

Tang, Su-Ni; Zhang, Jinhui; Wu, Wei; Jiang, Peixin; Puppala, Manohar; Zhang, Yong; Xing, Chengguo; Kim, Sung-Hoon; Jiang, Cheng; Lü, Junxuan

2015-01-01

We showed previously that daily gavage of Angelica gigas Nakai (AGN) root ethanolic extract starting 8 weeks of age inhibited growth of prostate epithelium and neuroendocrine carcinomas (NE-Ca) in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Since decursin (D) and its isomer decursinol angelate (DA) are major pyranocoumarins in AGN extract, we tested the hypothesis that D/DA represented active/prodrug compounds against TRAMP carcinogenesis. Three groups of male C57BL/6 TRAMP mice were gavage-treated daily with excipient vehicle, AGN (5 mg per mouse) or equimolar D/DA (3 mg per mouse) from 8 weeks to 16 or 28 weeks of age. Measurement of plasma and NE-Ca D, DA and their common metabolite decursinol indicated similar retention from AGN vs. D/DA dosing. The growth of TRAMP dorsolateral prostate (DLP) in AGN-and D/DA-treated mice was inhibited by 66% and 61% at 16 weeks and by 67% and 72% at 28 weeks, respectively. Survival of mice bearing NE-Ca to 28 weeks was improved by AGN, but not by D/DA. Nevertheless, AGN-and D/DA-treated mice had lower NE-Ca burden. Immunohistochemical and mRNA analyses of DLP showed AGN and D/DA exerted similar inhibition of TRAMP epithelial lesion progression and key cell cycle genes. Profiling of NE-Ca mRNA showed a greater scope of modulating angiogenesis, epithelial-mesenchymal-transition, invasion-metastasis and inflammation genes by AGN than D/DA. The data therefore support D/DA as probable active/prodrug compounds against TRAMP epithelial lesions, and they cooperate with non-pyranocoumarin compounds to fully express AGN efficacy against NE-Ca. PMID:26116406

Chemopreventive Effects of Korean Angelica versus Its Major Pyranocoumarins on Two Lineages of Transgenic Adenocarcinoma of Mouse Prostate Carcinogenesis.

PubMed

Tang, Su-Ni; Zhang, Jinhui; Wu, Wei; Jiang, Peixin; Puppala, Manohar; Zhang, Yong; Xing, Chengguo; Kim, Sung-Hoon; Jiang, Cheng; Lü, Junxuan

2015-09-01

We showed previously that daily gavage of Angelica gigas Nakai (AGN) root ethanolic extract starting 8 weeks of age inhibited growth of prostate epithelium and neuroendocrine carcinomas (NE-Ca) in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Because decursin (D) and its isomer decursinol angelate (DA) are major pyranocoumarins in AGN extract, we tested the hypothesis that D/DA represented active/prodrug compounds against TRAMP carcinogenesis. Three groups of male C57BL/6 TRAMP mice were gavage treated daily with excipient vehicle, AGN (5 mg per mouse), or equimolar D/DA (3 mg per mouse) from 8 weeks to 16 or 28 weeks of age. Measurement of plasma and NE-Ca D, DA, and their common metabolite decursinol indicated similar retention from AGN versus D/DA dosing. The growth of TRAMP dorsolateral prostate (DLP) in AGN- and D/DA-treated mice was inhibited by 66% and 61% at 16 weeks and by 67% and 72% at 28 weeks, respectively. Survival of mice bearing NE-Ca to 28 weeks was improved by AGN, but not by D/DA. Nevertheless, AGN- and D/DA-treated mice had lower NE-Ca burden. Immunohistochemical and mRNA analyses of DLP showed that AGN and D/DA exerted similar inhibition of TRAMP epithelial lesion progression and key cell-cycle genes. Profiling of NE-Ca mRNA showed a greater scope of modulating angiogenesis, epithelial-mesenchymal transition, invasion-metastasis, and inflammation genes by AGN than D/DA. The data therefore support D/DA as probable active/prodrug compounds against TRAMP epithelial lesions, and they cooperate with non-pyranocoumarin compounds to fully express AGN efficacy against NE-Ca. ©2015 American Association for Cancer Research.

Dopamine inhibits the function of Gr-1+CD115+ myeloid-derived suppressor cells through D1-like receptors and enhances anti-tumor immunity.

PubMed

Wu, Jin; Zhang, Ruihua; Tang, Ning; Gong, Zizhen; Zhou, Jiefei; Chen, Yingwei; Chen, Kang; Cai, Wei

2015-01-01

MDSCs accumulate in tumor-bearing animals and cancer patients and are a major factor responsible for cancer-induced immunosuppression that limits effective cancer immunotherapy. Strategies aimed at effectively inhibiting the function of MDSCs are expected to enhance host anti-tumor immunity and improve cancer immunotherapy significantly. The neurotransmitter DA has been found to have anti-cancer activity, but the underlying mechanism is poorly understood. In this study, we sought to investigate the therapeutic mechanism and efficacy of DA on the inhibition of cancer development via the regulation of MDSC functions. The regulation of the suppressive function of Gr-1(+)CD115(+) MDSCs by DA was determined by use of murine syngeneic LLC and B16 graft models treated with DA in vivo, as well as Gr-1(+)CD115(+) MDSCs isolated from these model treated with DA ex vivo. Here, we show that Gr-1(+)CD115(+) monocytic MDSCs express D1-like DA receptors. DA dramatically attenuated the inhibitory function of tumor-induced monocytic MDSCs on T cell proliferation and IFN-γ production via D1-like DA receptors and retarded tumor growth. DA and other D1 receptor agonists inhibited IFN-γ-induced NO production by MDSCs from tumor-bearing mice and cancer patients. Decreased NO production was, in part, mediated via the suppression of p-ERK and p-JNK. In conclusion, the neurotransmitter DA potently inhibits the suppressive function of MDSC and enhances anti-tumor immunity. Our finding provides a mechanistic basis for the use of DA or D1-like receptor agonists to overcome tumor-induced immunosuppression in cancer immunotherapy. © Society for Leukocyte Biology.

Reduced striatal dopamine DA D2 receptor function in dominant-negative GSK-3 transgenic mice.

PubMed

Gomez-Sintes, Raquel; Bortolozzi, Analia; Artigas, Francesc; Lucas, José J

2014-09-01

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with constitutive activity involved in cellular architecture, gene expression, cell proliferation, fate decision and apoptosis, among others. GSK-3 expression is particularly high in brain where it may be involved in neurological and psychiatric disorders such as Alzheimer׳s disease, bipolar disorder and major depression. A link with schizophrenia is suggested by the antipsychotic drug-induced GSK-3 regulation and by the involvement of the Akt/GSK-3 pathway in dopaminergic neurotransmission. Taking advantage of the previous development of dominant negative GSK-3 transgenic mice (Tg) showing a selective reduction of GSK-3 activity in forebrain neurons but not in dopaminergic neurons, we explored the relationship between GSK-3 and dopaminergic neurotransmission in vivo. In microdialysis experiments, local quinpirole (DA D2-R agonist) in dorsal striatum reduced dopamine (DA) release significantly less in Tg mice than in wild-type (WT) mice. However, local SKF-81297 (selective DA D1-R agonist) in dorsal striatum reduced DA release equally in both control and Tg mice indicating a comparable function of DA D1-R in the direct striato-nigral pathway. Likewise, systemic quinpirole administration - acting preferentially on presynaptic DA D2- autoreceptors to modulate DA release-reduced striatal DA release similarly in both control and Tg mice. Quinpirole reduced locomotor activity and induced c-fos expression in globus pallidus (both striatal DA D2-R-mediated effects) significantly more in WT than in Tg mice. Taking together, the present results show that dominant negative GSK-3 transgenic mice show reduced DA D2-R-mediated function in striatum and further support a link between dopaminergic neurotransmission and GSK-3 activity. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Effect of parasitic infection on dopamine biosynthesis in dopaminergic cells

PubMed Central

Martin, H.L.; Alsaady, I.; Howell, G.; Prandovszky, E.; Peers, C.; Robinson, P.; McConkey, G.A.

2015-01-01

Infection by the neurotropic agent Toxoplasma gondii alters rodent behavior and can result in neuropsychiatric symptoms in humans. Little is understood regarding the effects of infection on host neural processes but alterations to dopaminergic neurotransmission are implicated. We have previously reported elevated levels of dopamine (DA) in infected dopaminergic cells however the involvement of the host enzymes and fate of the produced DA were not defined. In order to clarify the effects of infection on host DA biosynthetic enzymes and DA packaging we examined enzyme levels and activity and DA accumulation and release in T. gondii-infected neurosecretory cells. Although the levels of the host tyrosine hydroxylase (TH) and DOPA decarboxylase and AADC (DDC) did not change significantly in infected cultures, DDC was found within the parasitophorous vacuole (PV), the vacuolar compartment where the parasites reside, as well as in the host cytosol in infected dopaminergic cells. Strikingly, DDC was found within the intracellular parasite cysts in infected brain tissue. This finding could provide some explanation for observations of DA within tissue cysts in infected brain as a parasite-encoded enzyme with TH activity was also localized within tissue cysts. In contrast, cellular DA packaging appeared unchanged in single-cell microamperometry experiments and only a fraction of the increased DA was accessible to high potassium-induced release. This study provides some understanding of how this parasite produces elevated DA within dopaminergic cells without the toxic ramifications of free cytosolic DA. The mechanism for synthesis and packaging of DA by T. gondii-infected dopaminergic cells may have important implications for the effects of chronic T. gondii infection on humans and animals. PMID:26297895

Cytochrome P450 isoforms in the Metabolism of Decursin and Decursinol Angelate from Korean Angelica

PubMed Central

ZHANG, Jinhui; LI, Li; TANG, Suni; HALE, Thomas W.; XING, Chengguo; JIANG, Cheng; LÜ, Junxuan

2016-01-01

We have shown that the in vitro hepatic microsomal metabolism of pyranocoumarin compound decursinol angelate (DA) to decursinol (DOH) exclusively requires cytochrome P450 enzymes (CYP) whereas the conversion of its isomer decursin (D) to DOH can be mediated by CYP and esterase(s). To provide insight into specific isoforms involved, here we show with recombinant human CYP that 2C19 was the most active at metabolizing D and DA in vitro followed by 3A4. With carboxylesterases (CES), D was hydrolyzed by CES2 but not CES1, and DA was resistant to both CES1 and CES2. In human liver microsomal preparation, general CYP inhibitor 1-aminobenzotriazole (ABT) and respective competitive inhibitors for 2C19 and 3A4, (+)-N-3-benzylnirvanol and ketoconazole, substantially retarded the metabolism of DA and, to a lesser extent, of D. In healthy human subjects from a single-dose pharmacokinetic study, 2C19 extensive metabolizer genotype (2C19*17 allele) tended to have less plasma DA AUC0–48h and poor metabolizer genotype (2C19*2 allele) tended to have greater DA AUC0–48h. In mice given a single dose of D/DA, pretreatment with ABT boosted the plasma and prostate levels of D and DA by more than an order of magnitude. Taken together, our findings suggest that CYP isoforms 2C19 and 3A4 may play a crucial role in the first pass liver metabolism of DA and, to a lesser extent, that of D in humans. Pharmacogenetics with respect to CYP genotypes and interactions among CYP inhibitor drugs and D/DA should therefore be considered in designing future translation studies of DA and/or D. PMID:26394652

Cytochrome P450 Isoforms in the Metabolism of Decursin and Decursinol Angelate from Korean Angelica.

PubMed

Zhang, Jinhui; Li, Li; Tang, Suni; Hale, Thomas W; Xing, Chengguo; Jiang, Cheng; Lü, Junxuan

2015-01-01

We have shown that the in vitro hepatic microsomal metabolism of pyranocoumarin compound decursinol angelate (DA) to decursinol (DOH) exclusively requires cytochrome P450 (CYP) enzymes, whereas the conversion of its isomer decursin (D) to DOH can be mediated by CYP and esterase(s). To provide insight into specific isoforms involved, here we show with recombinant human CYP that 2C19 was the most active at metabolizing D and DA in vitro followed by 3A4. With carboxylesterases (CES), D was hydrolyzed by CES2 but not CES1, and DA was resistant to both CES1 and CES2. In human liver microsomal (HLM) preparation, the general CYP inhibitor 1-aminobenzotriazole (ABT) and respective competitive inhibitors for 2C19 and 3A4, (+)-N-3-benzylnirvanol (NBN) and ketoconazole substantially retarded the metabolism of DA and, to a lesser extent, of D. In healthy human subjects from a single-dose pharmacokinetic (PK) study, 2C19 extensive metabolizer genotype (2C19*17 allele) tended to have less plasma DA AUC0-48h and poor metabolizer genotype (2C19*2 allele) tended to have greater DA AUC0-48h. In mice given a single dose of D/DA, pretreatment with ABT boosted the plasma and prostate levels of D and DA by more than an order of magnitude. Taken together, our findings suggest that CYP isoforms 2C19 and 3A4 may play a crucial role in the first pass liver metabolism of DA and, to a lesser extent, that of D in humans. Pharmacogenetics with respect to CYP genotypes and interactions among CYP inhibitor drugs and D/DA should therefore be considered in designing future translation studies of DA and/or D.

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

Barrett, Christopher A.; Martinez, Alonzo; McNamara, Bruce K.

International Atom Energy Agency (IAEA) safeguard verification measures in gaseous centrifuge enrichment plants (GCEPs) rely on environmental sampling, non-destructive assay (NDA), and destructive assay (DA) sampling and analysis to determine uranium enrichment. UF6 bias defect measurements are made by DA sampling and analysis to assure that enrichment is consistent with declarations. DA samples are collected from a limited number of cylinders for high precision, offsite mass spectrometer analysis. Samples are typically drawn from a sampling tap into a UF6 sample bottle, then packaged, sealed, and shipped under IAEA chain of custody to an offsite analytical laboratory. Future DA safeguard measuresmore » may require improvements in efficiency and effectiveness as GCEP capacities increase and UF6 shipping regulations become increasingly more restrictive. The Pacific Northwest National Laboratory (PNNL) DA sampler concept and Laser Ablation Absorption Ratio Spectrometry (LAARS) assay method are under development to potentially provide DA safeguard tools that increase inspection effectiveness and reduce sample shipping constraints. The PNNL DA sampler concept uses a handheld sampler to collect DA samples for either onsite LAARS assay or offsite laboratory analysis. The DA sampler design will use a small sampling planchet that is coated with an adsorptive film to collect controlled quantities of UF6 gas directly from a cylinder or process sampling tap. Development efforts are currently underway at PNNL to enhance LAARS assay performance to allow high-precision onsite bias defect measurements. In this paper, we report on the experimental investigation to develop adsorptive films for the PNNL DA sampler concept. These films are intended to efficiently capture UF6 and then stabilize the collected DA sample prior to onsite LAARS or offsite laboratory analysis. Several porous material composite films were investigated, including a film designed to maximize the chemical adsorption and binding of gaseous UF6 onto the sampling planchet.« less

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

Nunes, O. A. C., E-mail: oacn@unb.br

We study the interaction of Dirac Fermions in monolayer graphene on a GaAs substrate in an applied electric field by the combined action of the extrinsic potential of piezoelectric surface acoustical phonons of GaAs (piezoelectric acoustical (PA)) and of the intrinsic deformation potential of acoustical phonons in graphene (deformation acoustical (DA)). We find that provided the dc field exceeds a threshold value, emission of piezoelectric (PA) and deformation (DA) acoustical phonons can be obtained in a wide frequency range up to terahertz at low and high temperatures. We found that the phonon amplification rate R{sup PA,DA} scales with T{sub BG}{supmore » S−1} (S=PA,DA), T{sub BG}{sup S} being the Block−Gru{sup ¨}neisen temperature. In the high-T Block−Gru{sup ¨}neisen regime, extrinsic PA phonon scattering is suppressed by intrinsic DA phonon scattering, where the ratio R{sup PA}/R{sup DA} scales with ≈1/√(n), n being the carrier concentration. We found that only for carrier concentration n≤10{sup 10}cm{sup −2}, R{sup PA}/R{sup DA}>1. In the low-T Block−Gru{sup ¨}neisen regime, and for n=10{sup 10}cm{sup −2}, the ratio R{sup PA}/R{sup DA} scales with T{sub BG}{sup DA}/T{sub BG}{sup PA}≈7.5 and R{sup PA}/R{sup DA}>1. In this regime, PA phonon dominates the electron scattering and R{sup PA}/R{sup DA}<1 otherwise. This study is relevant to the exploration of the acoustic properties of graphene and to the application of graphene as an acoustical phonon amplifier and a frequency-tunable acoustical phonon device.« less

Effect of DA-9701 on the Normal Motility and Clonidine-induced Hypomotility of the Gastric Antrum in Rats

PubMed Central

Kang, Je Wook; Han, Dae Kyeong; Kim, Ock Nyun; Lee, Kwang Jae

2016-01-01

Background/Aims DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. Methods A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidine-pretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. Results Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. Conclusions DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition. PMID:26755679

Differential involvement of dopamine D-1 and D-2 receptors in the circling behaviour induced by apomorphine, SK & F 38393, pergolide and LY 171555 in 6-hydroxydopamine-lesioned rats.

PubMed

Arnt, J; Hyttel, J

1985-01-01

The antagonistic effect of dopamine (DA) D-1 and D-2 antagonists against circling behaviour induced by various DA agonists in 6-OHDA-lesioned rats has been investigated. DA D-1/D-2 selectivity of agonists in vitro was measured by the stimulatory effect on DA-sensitive adenylate cyclase in rat striatal homogenates (D-1), the inhibitory effect on electrically-induced release of 3H-DA in rabbit striatal slices (D-2) and the affinity to 3H-piflutixol (D-1) and 3H-spiroperidol (D-2) binding sites in rat striatal membranes. The contralateral circling behaviour induced by the DA D-1 agonist SK & F 38393 was blocked by the DA D-1 antagonist, SCH 23390, and by the mixed DA D-1/D-2 antagonist cis(Z)-flupentixol, but was not influenced by the DA D-2 antagonists spiroperidol and clebopride. In contrast, circling behaviour induced by the preferential DA D-2 agonists pergolide and LY 171555 was blocked by clebopride, spiroperidol, and cis(Z)-flupentixol, but weakly or not influenced by SCH 23390. Apomorphine-induced circling behaviour was blocked by cis(Z)-flupentixol, partially antagonized by SCH 23390 and clebopride but not inhibited by spiroperidol, although the time-course of circling was changed. Combinations of SCH 23390 with spiroperidol or clebopride in low doses completely blocked the effect of apomorphine. These results indicate that DA D-1 and D-2 receptors mediate circling behaviour through separate mechanisms which can be independently manipulated with respective agonists and antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain.

PubMed

Volkow, N D; Wang, G; Fowler, J S; Logan, J; Gerasimov, M; Maynard, L; Ding, Y; Gatley, S J; Gifford, A; Franceschi, D

2001-01-15

Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug in children for the treatment of attention deficit hyperactivity disorder (ADHD), yet the mechanisms responsible for its therapeutic effects are poorly understood. Whereas methylphenidate blocks the dopamine transporter (main mechanism for removal of extracellular dopamine), it is unclear whether at doses used therapeutically it significantly changes extracellular dopamine (DA) concentration. Here we used positron emission tomography and [(11)C]raclopride (D2 receptor radioligand that competes with endogenous DA for binding to the receptor) to evaluate whether oral methylphenidate changes extracellular DA in the human brain in 11 healthy controls. We showed that oral methylphenidate (average dose 0.8 +/- 0.11 mg/kg) significantly increased extracellular DA in brain, as evidenced by a significant reduction in B(max)/K(d) (measure of D2 receptor availability) in striatum (20 +/- 12%; p < 0.0005). These results provide direct evidence that oral methylphenidate at doses within the therapeutic range significantly increases extracellular DA in human brain. This result coupled with recent findings of increased dopamine transporters in ADHD patients (which is expected to result in reductions in extracellular DA) provides a mechanistic framework for the therapeutic efficacy of methylphenidate. The increase in DA caused by the blockade of dopamine transporters by methylphenidate predominantly reflects an amplification of spontaneously released DA, which in turn is responsive to environmental stimulation. Because DA decreases background firing rates and increases signal-to-noise in target neurons, we postulate that the amplification of weak DA signals in subjects with ADHD by methylphenidate would enhance task-specific signaling, improving attention and decreasing distractibility. Alternatively methylphenidate-induced increases in DA, a neurotransmitter involved with motivation and reward, could enhance the salience of the task facilitating the "interest that it elicits" and thus improving performance.

The Effect of DA-9701 in Opioid-induced Bowel Dysfunction of Guinea Pig.

PubMed

Hussain, Zahid; Rhee, Kwang Won; Lee, Young Ju; Park, Hyojin

2016-07-30

Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics. DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber has promising effects on GI motor function. Therefore, we aim to evaluate the prokinetic effects of DA-9701 in an OIBD model of guinea pig. The ileal and distal colon muscle contraction in presence of different doses of DA-9701, morphine, and combination (morphine + DA-9701) was measured by tissue bath study. The prokinetic effect of DA-9701 was assessed by charcoal transit and fecal pellet output assay in an OIBD model of guinea pig. DA-9701 significantly increased the amplitude and area under the curve of ileal muscle contraction, while there was insignificant effect on the distal colon compared to the control. The maximal amplitude of ileal muscle contraction was acquired at a concentration of 10 μg/mL of DA-9701. In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control. Morphine delayed both upper (P < 0.01) and lower (P < 0.05) GI transit, and delayed GI transit was restored by the administration of DA-9701. Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles. DA-9701 significantly increased the amplitude of contraction of the ileal muscle, however the distal colon muscle contraction was insignificant. Additionally, it restored delayed upper and lower GI transit in an OIBD model of guinea pig, and it might prove to be a useful candidate drug in a clinical trial for OIBD.

Gβγ subunit activation promotes dopamine efflux through the dopamine transporter

PubMed Central

Garcia-Olivares, J; Baust, T; Harris, S; Hamilton, P; Galli, A; Amara, SG; Torres, GE

2018-01-01

The dopamine transporter (DAT) is an important regulator of brain dopamine (DA) homeostasis, controlling the intensity and duration of DA signaling. DAT is the target for psychostimulants—like cocaine and amphetamine—and plays an important role in neuropsychiatric disorders, including attention-deficit hyperactivity disorder and drug addiction. Thus, a thorough understanding of the mechanisms that regulate DAT function is necessary for the development of clinical interventions to treat DA-related brain disorders. Previous studies have revealed a plethora of protein–protein interactions influencing DAT cellular localization and activity, suggesting that the fine-tuning of DA homeostasis involves multiple mechanisms. We recently reported that G-protein beta-gamma (Gβγ) subunits bind directly to DAT and decrease DA clearance. Here we show that Gβγ induces the release of DA through DAT. Specifically, a Gβγ-binding/activating peptide, mSIRK, increases DA efflux through DAT in heterologous cells and primary dopaminergic neurons in culture. Addition of the Gβγ inhibitor gallein or DAT inhibitors prevents this effect. Residues 582 to 596 in the DAT carboxy terminus were identified as the primary binding site of Gβγ. A TAT peptide containing the Gβγ-interacting domain of DAT blocked the ability of mSIRK to induce DA efflux, consistent with a direct interaction of Gβγ with the transporter. Finally, activation of a G-protein-coupled receptor, the muscarinic M5R, results in DAT-mediated DA efflux through a Gβγ-dependent mechanism. Collectively, our data show that Gβγ interacts with DAT to promote DA efflux. This novel mechanism may have important implications in the regulation of brain DA homeostasis. PMID:28894302

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

PubMed

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-07-01

The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

Effect of DA-9701 on the Normal Motility and Clonidine-induced Hypomotility of the Gastric Antrum in Rats.

PubMed

Kang, Je Wook; Han, Dae Kyeong; Kim, Ock Nyun; Lee, Kwang Jae

2016-04-30

DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidinepretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition.

Biochemical and mass spectrometric characterization of the human CB2 cannabinoid receptor expressed in Pichia pastoris--importance of correct processing of the N-terminus.

PubMed

Zhang, Rundong; Kim, Tae-Kang; Qiao, Zhaun-Hong; Cai, Jian; Pierce, William M; Song, Zhao-Hui

2007-10-01

This study was conducted to optimize the expression of human CB2 cannabinoid receptors in methylotrophic yeast Pichia pastoris (P. pastoris). Two major species of expressed CB2 proteins were seen on Western blot, i.e., a 42 kDa band which matches the calculated molecular weight for tagged CB2, and a 52/55 kDa doublet. Treatment of membranes with N-glycosidase F or inclusion of tunicamycin in the culture medium during induction resulted in the disappearance of the 55 kDa, but not the 52 kDa band, suggesting that the 3 kDa extra in the 55 kDa band is due to N-glycosylation, but the 10 kDa extra in the 52 kDa band is not due to N-glycosylation. Anti-FLAG M1 antibody had a much higher preference for the 42 kDa band over the 52/55 kDa doublet, and a 10 kDa fragment recognized by anti-FLAG M2 antibody was generated by CNBr digestion of the 52/55 doublet. These data strongly support the hypothesis that the 10 kDa increase in molecular weight was due to unprocessed alpha-factor sequence. This conclusion was further validated by finding several peptide sequences for alpha-factor fragments at the N-terminal of the CB2 receptor using pepsin/chymotrypsin digestion and LC/MS/MS approaches. Importantly, unprocessed alpha-factor was found to be associated with poor ligand binding. In addition, controlling the level of CB2 protein expression was found to be critical for minimizing the presence of unprocessed alpha-factor sequence. The information gained from this study should aid the proper expression of not only CB2 receptor but also other members of the GPCR family in P. pastoris.

Comprehensive enzymatic analysis of the amylolytic system in the digestive fluid of the sea hare, Aplysia kurodai: Unique properties of two α-amylases and two α-glucosidases.

PubMed

Tsuji, Akihiko; Nishiyama, Nami; Ohshima, Miki; Maniwa, Saori; Kuwamura, Shuji; Shiraishi, Masataka; Yuasa, Keizo

2014-01-01

Sea lettuce (Ulva pertusa) is a nuisance species of green algae that is found all over the world. East-Asian species of the marine gastropod, the sea hare Aplysia kurodai, shows a clear feeding preference for sea lettuce. Compared with cellulose, sea lettuce contains a higher amount of starch as a storage polysaccharide. However, the entire amylolytic system in the digestive fluid of A. kurodai has not been studied in detail. We purified α-amylases and α-glucosidases from the digestive fluid of A. kurodai and investigated the synergistic action of these enzymes on sea lettuce. A. kurodai contain two α-amylases (59 and 80 kDa) and two α-glucosidases (74 and 86 kDa). The 59-kDa α-amylase, but not the 80-kDa α-amylase, was markedly activated by Ca(2+) or Cl(-). Both α-amylases degraded starch and maltoheptaose, producing maltotriose, maltose, and glucose. Glucose production from starch was higher with 80-kDa α-amylase than with 59-kDa α-amylase. Kinetic analysis indicated that 74-kDa α-glucosidase prefers short α-1,4-linked oligosaccharide, whereas 86-kDa α-glucosidase prefers large α-1,6 and α-1,4-linked polysaccharides such as glycogen. When sea lettuce was used as a substrate, a 2-fold greater amount of glucose was released by treatment with 59-kDa α-amylase and 74-kDa α-glucosidase than by treatment with 45-kDa cellulase and 210-kDa β-glucosidase of A. kurodai. Unlike mammals, sea hares efficiently digest sea lettuce to glucose by a combination of two α-amylases and two α-glucosidases in the digestive fluids without membrane-bound maltase-glucoamylase and sucrase-isomaltase complexes.

Dopamine acting at D1-like, D2-like and α1-adrenergic receptors differentially modulates theta and gamma oscillatory activity in primary motor cortex.

PubMed

Özkan, Mazhar; Johnson, Nicholas W; Sehirli, Umit S; Woodhall, Gavin L; Stanford, Ian M

2017-01-01

The loss of dopamine (DA) in Parkinson's is accompanied by the emergence of exaggerated theta and beta frequency neuronal oscillatory activity in the primary motor cortex (M1) and basal ganglia. DA replacement therapy or deep brain stimulation reduces the power of these oscillations and this is coincident with an improvement in motor performance implying a causal relationship. Here we provide in vitro evidence for the differential modulation of theta and gamma activity in M1 by DA acting at receptors exhibiting conventional and non-conventional DA pharmacology. Recording local field potentials in deep layer V of rat M1, co-application of carbachol (CCh, 5 μM) and kainic acid (KA, 150 nM) elicited simultaneous oscillations at a frequency of 6.49 ± 0.18 Hz (theta, n = 84) and 34.97 ± 0.39 Hz (gamma, n = 84). Bath application of DA resulted in a decrease in gamma power with no change in theta power. However, application of either the D1-like receptor agonist SKF38393 or the D2-like agonist quinpirole increased the power of both theta and gamma suggesting that the DA-mediated inhibition of oscillatory power is by action at other sites other than classical DA receptors. Application of amphetamine, which promotes endogenous amine neurotransmitter release, or the adrenergic α1-selective agonist phenylephrine mimicked the action of DA and reduced gamma power, a result unaffected by prior co-application of D1 and D2 receptor antagonists SCH23390 and sulpiride. Finally, application of the α1-adrenergic receptor antagonist prazosin blocked the action of DA on gamma power suggestive of interaction between α1 and DA receptors. These results show that DA mediates complex actions acting at dopamine D1-like and D2-like receptors, α1 adrenergic receptors and possibly DA/α1 heteromultimeric receptors to differentially modulate theta and gamma activity in M1.

Comprehensive enzymatic analysis of the amylolytic system in the digestive fluid of the sea hare, Aplysia kurodai: Unique properties of two α-amylases and two α-glucosidases

PubMed Central

Tsuji, Akihiko; Nishiyama, Nami; Ohshima, Miki; Maniwa, Saori; Kuwamura, Shuji; Shiraishi, Masataka; Yuasa, Keizo

2014-01-01

Sea lettuce (Ulva pertusa) is a nuisance species of green algae that is found all over the world. East-Asian species of the marine gastropod, the sea hare Aplysia kurodai, shows a clear feeding preference for sea lettuce. Compared with cellulose, sea lettuce contains a higher amount of starch as a storage polysaccharide. However, the entire amylolytic system in the digestive fluid of A. kurodai has not been studied in detail. We purified α-amylases and α-glucosidases from the digestive fluid of A. kurodai and investigated the synergistic action of these enzymes on sea lettuce. A. kurodai contain two α-amylases (59 and 80 kDa) and two α-glucosidases (74 and 86 kDa). The 59-kDa α-amylase, but not the 80-kDa α-amylase, was markedly activated by Ca2+ or Cl−. Both α-amylases degraded starch and maltoheptaose, producing maltotriose, maltose, and glucose. Glucose production from starch was higher with 80-kDa α-amylase than with 59-kDa α-amylase. Kinetic analysis indicated that 74-kDa α-glucosidase prefers short α-1,4-linked oligosaccharide, whereas 86-kDa α-glucosidase prefers large α-1,6 and α-1,4-linked polysaccharides such as glycogen. When sea lettuce was used as a substrate, a 2-fold greater amount of glucose was released by treatment with 59-kDa α-amylase and 74-kDa α-glucosidase than by treatment with 45-kDa cellulase and 210-kDa β-glucosidase of A. kurodai. Unlike mammals, sea hares efficiently digest sea lettuce to glucose by a combination of two α-amylases and two α-glucosidases in the digestive fluids without membrane-bound maltase–glucoamylase and sucrase–isomaltase complexes. PMID:25161866

cis-4-Decenoic and decanoic acids impair mitochondrial energy, redox and Ca(2+) homeostasis and induce mitochondrial permeability transition pore opening in rat brain and liver: Possible implications for the pathogenesis of MCAD deficiency.

PubMed

Amaral, Alexandre Umpierrez; Cecatto, Cristiane; da Silva, Janaína Camacho; Wajner, Alessandro; Godoy, Kálita Dos Santos; Ribeiro, Rafael Teixeira; Wajner, Moacir

2016-09-01

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is biochemically characterized by tissue accumulation of octanoic (OA), decanoic (DA) and cis-4-decenoic (cDA) acids, as well as by their carnitine by-products. Untreated patients present episodic encephalopathic crises and biochemical liver alterations, whose pathophysiology is poorly known. We investigated the effects of OA, DA, cDA, octanoylcarnitine (OC) and decanoylcarnitine (DC) on critical mitochondrial functions in rat brain and liver. DA and cDA increased resting respiration and diminished ADP- and CCCP-stimulated respiration and complexes II-III and IV activities in both tissues. The data indicate that these compounds behave as uncouplers and metabolic inhibitors of oxidative phosphorylation. Noteworthy, metabolic inhibition was more evident in brain as compared to liver. DA and cDA also markedly decreased mitochondrial membrane potential, NAD(P)H content and Ca(2+) retention capacity in Ca(2+)-loaded brain and liver mitochondria. The reduction of Ca(2+) retention capacity was more pronounced in liver and totally prevented by cyclosporine A and ADP, as well as by ruthenium red, demonstrating the involvement of mitochondrial permeability transition (mPT) and Ca(2+). Furthermore, cDA induced lipid peroxidation in brain and liver mitochondria and increased hydrogen peroxide formation in brain, suggesting the participation of oxidative damage in cDA-induced alterations. Interestingly, OA, OC and DC did not alter the evaluated parameters, implying lower toxicity for these compounds. Our results suggest that DA and cDA, in contrast to OA and medium-chain acylcarnitines, disturb important mitochondrial functions in brain and liver by multiple mechanisms that are possibly involved in the neuropathology and liver alterations observed in MCAD deficiency. Copyright © 2016 Elsevier B.V. All rights reserved.

Counter-regulation by insulin and isoprenaline of a prominent fat-associated phosphoprotein doublet in rat adipocytes.

PubMed

Mooney, R A; Bordwell, K L

1991-03-01

1. In the adipocyte, phosphorylation/dephosphorylation of regulatory proteins is a common mechanism of metabolic regulation. We have observed a very prominent phosphoprotein doublet of 61 kDa and 63 kDa in rat adipocytes that is markedly responsive to hormones. The 63 kDa band was the predominant phosphoprotein in the cell in response to 0.1 microM-isoprenaline, whereas the 61 kDa band was nearly absent. Insulin alone did not alter 32P incorporation into the doublet, but partially counteracted the effects of isoprenaline, decreasing label in the 63 kDa band by as much as 50% and resulting in the reappearance of the 61 kDa band. 2. Subcellular fractionation demonstrated that both phosphoprotein bands were fat-associated. Neither insulin nor isoprenaline altered this localization. Peptide maps (one-dimensional) of the 61/63 kDa bands demonstrated close sequence similarity. Amino acid analysis revealed the presence of phosphoserine and phosphothreonine. The latter was more prominent in the 61 kDa band. Isoprenaline caused an absolute increase in both phosphoamino acids. 3. Permeabilization of 32P-labelled isoprenaline-treated cells with digitonin initiated rapid dephosphorylation of the 63 kDa band, with reappearance of the 61 kDa band. Insulin increased the rate of dephosphorylation by 2-3-fold when present with isoprenaline before permeabilization. 4. In permeabilized adipocytes, cyclic AMP (1 microM-1 mM) increased phosphorylation of the 61/63 kDa doublet by 4-10-fold in the presence of [gamma-32P]ATP, but insulin had no effect. 5. We conclude that this prominent phosphoprotein, migrating as a 61/63 kDa doublet, is coupled to the cyclic AMP-dependent protein kinase and is associated with an insulin-stimulated phosphoprotein phosphatase activity. This fat-associated phosphoprotein, which is under counter-regulatory hormonal control, may play a role in hormone-dependent lipid metabolism.

DA-6034-induced mucin secretion via Ca2+-dependent pathways through P2Y receptor stimulation.

PubMed

Lee, Hun; Kim, Eung Kweon; Kim, Ji Yeon; Yang, Yu-Mi; Shin, Dong Min; Kang, Kyung Koo; Kim, Tae-im

2014-09-11

We evaluated whether DA-6034 is involved in mucin secretion via P2Y receptor activation and/or intracellular Ca2+ concentration ([Ca2+]i) change. Also, we investigated the effect of P2Y receptor inhibitors or Ca2+ chelators on the DA-6034-induced mucin secretion and [Ca2+]i increases. Effects of DA-6034 on mucin expression in primary, cultured, conjunctival epithelial cells was studied using RT-PCR, Western blot analysis, and periodic acid-schiff (PAS) staining. To evaluate thin film layer thickness generated by mucin and fluid secretion, cells were incubated in DA-6034 with/without P2Y antagonists or extracellular/intracellular Ca2+ chelators, and were imaged with confocal microscope using Texas Red-dextran dye. In addition, DA-6034-induced Ca2+-dependent Cl- channels opening was evaluated using perforated patch clamp. Fluo-4/AM was used to measure changes in [Ca2+]i induced by DA-6034 in Ca2+-free or Ca2+-containing buffered condition, as well as P2Y antagonists. DA-6034 induced the expression of mucin genes, production of mucin protein, and increase of number of mucin-secreting cells. P2Y antagonists inhibited DA-6034-induced mucin and fluid secretion, which was also affected by extracellular/intracellular Ca2+ chelators. DA-6034 stimulated Cl- channel opening and [Ca2+]i elevation. Further, [Ca2+]i increases induced by DA-6034 were lacking in either P2Y antagonists or Ca2+-free buffered condition, and diminished when endoplasmic reticulum Ca2+ was depleted by cyclopiazonic acid in Ca2+-free buffered condition. This study demonstrated that DA-6034 has a potential to induce mucin secretion via Ca2+-dependent pathways through P2Y receptors in multilayer, cultured, human conjunctival epithelial cells. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Analysis of suffering at work in Family Health Support Centers.

PubMed

Nascimento, Débora Dupas Gonçalves do; Oliveira, Maria Amélia de Campos

2016-01-01

Analyzing the work process in the Family Health Support Center. An exploratory, descriptive case study using a qualitative approach. Focus groups were conducted with 20 workers of a Family Health Support Center, and the empirical material was subjected to content analysis technique and analyzed in light of Work Psychodynamics. The category of suffering is presented herein as arising from the dialectical contradiction between actual work and prescribed work, from resistance to the Family Health Support Center's proposal and a lack of understanding of their role; due to an immediatist and curative culture of the users and the Family Health Strategy; of the profile, overload and identification with work. The dialectical contradiction between expectations from Family Health Strategy teams and the work in the Family Health Support Center compromises its execution and creates suffering for workers. Analisar o processo de trabalho no Núcleo de Apoio à Saúde da Família. Estudo de caso exploratório, descritivo e de abordagem qualitativa. Grupos focais foram realizados com 20 trabalhadores do Núcleo de Apoio à Saúde da Família, o material empírico foi submetido à técnica de análise de conteúdo e analisado à luz da Psicodinâmica do Trabalho. Apresenta-se aqui a categoria sofrimento que neste estudo decorre da contradição dialética entre o trabalho real e o trabalho prescrito, da resistência à proposta do Núcleo de Apoio à Saúde da Família e da falta de compreensão de seu papel; da cultura imediatista e curativa do usuário e da Estratégia Saúde da Família; do perfil, sobrecarga e identificação com o trabalho. A contradição dialética entre expectativas das equipes da Estratégia Saúde da Família e o trabalho no Núcleo de Apoio à Saúde da Família compromete sua efetivação e gera sofrimento aos trabalhadores.

Identification of a novel 82 kDa proMMP-9 species associated with the surface of leukaemic cells: (auto-)catalytic activation and resistance to inhibition by TIMP-1

PubMed Central

Ries, Christian; Pitsch, Thomas; Mentele, Reinhard; Zahler, Stefan; Egea, Virginia; Nagase, Hideaki; Jochum, Marianne

2007-01-01

MMP-9 (matrix metalloproteinase 9) plays a critical role in tumour progression. Although the biochemical properties of the secreted form of proMMP-9 are well characterized, little is known about the function and activity of cell surface-associated proMMP-9. We purified a novel 82 kDa species of proMMP-9 from the plasma membrane of THP-1 leukaemic cells, which has substantial differences from the secreted 94 kDa proMMP-9. The 82 kDa form was not detected in the medium even upon stimulation with a phorbol ester. It is truncated by nine amino acid residues at its N-terminus, lacks O-linked oligosaccharides present in the 94 kDa proMMP-9, but retains N-linked carbohydrates. Incubation of 94 kDa proMMP-9 with MMP-3 generated the well-known 82 kDa active form, but the 82 kDa proMMP-9 was converted into an active species of 35 kDa, which was also produced by autocatalytic processing in the absence of activating enzymes. The activated 35 kDa MMP-9 efficiently degraded gelatins, native collagen type IV and fibronectin. The enzyme was less sensitive to TIMP-1 (tissue inhibitor of metalloproteinase 1) inhibition with IC50 values of 82 nM compared with 1 nM for the 82 kDa active MMP-9. The synthetic MMP inhibitor GM6001 blocked the activity of both enzymes, with similar IC50 values below 1 nM. The 82 kDa proMMP-9 is also produced in HL-60 and NB4 leukaemic cell lines as well as ex vivo leukaemic blast cells. It is, however, absent from neutrophils and mononuclear cells isolated from peripheral blood of healthy individuals. Thus, the 82 kDa proMMP-9 expressed on the surface of malignant cells may escape inhibition by natural TIMP-1, thereby facilitating cellular invasion in vivo. PMID:17489740

Biosynthesis, processing, and subcellular localization of rat spermbeta-D-galactosidase.

PubMed

Chayko, C A; Orgebin-Crist, M C; Skudlarek, M D; Tulsiani, D R

2000-09-01

During spermatogenesis, spermatids synthesize constituent proteins present in mature spermatozoa; however, little information exists on the molecular processes involved. In previous studies, this laboratory reported the characterization of rat sperm beta-D-galactosidase. In this paper, we report the localization of this enzyme along with its biosynthesis and processing. An antibody against rat luminal fluid beta-D-galactosidase was used to immunolocalize the enzyme in the testis and in epididymal spermatozoa. We found that beta-D-galactosidase is localized within the acrosomal cap of spermatids and in the acrosome and cytoplasmic droplet of epididymal spermatozoa. A combination of germ cell radiolabeling, immunoprecipitation, SDS-PAGE, and autoradiography revealed that spermatids produce two forms of beta-D-galactosidase, 90 and 88 kDa. During pulse-chase analysis, a 56-kDa form appeared. Treatment of beta-D-galactosidase immunoprecipitates from testicular spermatozoa with N-glycanase or Endo H revealed that both the 90- and 88-kDa forms become a 70-kDa polypeptide on SDS-PAGE. Since Endo H or N-glycanase treatment provided similar results, the presence of extensive N-linked high mannose/hybrid-type glycans on these proteins is indicated. Treatment of the 56-kDa form of beta-D-galactosidase with Endo H or N-glycanase resulted in the appearance of 52- and 50-kDa forms, respectively. This result suggests that the 56-kDa form contains N-linked high mannose/hybrid as well as complex oligosaccharides. During epididymal maturation, the 90-kDa form of beta-D-galactosidase persists in caput epididymal spermatozoa and is gradually converted to a major 74-kDa form in cauda spermatozoa. In addition to the 90- to 74-kDa forms, cauda spermatozoa show a 56- to 52-kDa form on Western immunoblots. Since only the high-molecular weight forms of beta-D-galactosidase are present on immunoblots of isolated sperm heads, we suggest that they are acrosomal in origin and that the 56-kDa form, which is processed to 52 kDa in cauda spermatozoa, is associated with the cytoplasmic droplet.

Peer Deviance, Parental Divorce, and Genetic Risk in the Prediction of Drug Abuse in a Nationwide Swedish Sample

PubMed Central

Kendler, Kenneth S.; Ohlsson, Henrik; Sundquist, Kristina; Sundquist, Jan

2014-01-01

IMPORTANCE Peer deviance (PD) strongly predicts externalizing psychopathologic conditions but has not been previously assessable in population cohorts. We sought to develop such an index of PD and to clarify its effects on risk of drug abuse (DA). OBJECTIVES To examine how strongly PD increases the risk of DA and whether this community-level liability indicator interacts with key DA risk factors at the individual and family levels. DESIGN, SETTING, AND PARTICIPANTS Studies of future DA registration in 1 401 698 Swedish probands born from January 1, 1970, through December 31, 1985, and their adolescent peers in approximately 9200 small community areas. Peer deviance was defined as the proportion of individuals born within 5 years of the proband living in the same small community when the proband was 15 years old who eventually were registered for DA. MAIN OUTCOMES AND MEASURES Drug abuse recorded in medical, legal, or pharmacy registry records. RESULTS Peer deviance was associated with future DA in the proband, with rates of DA in older and male peers more strongly predictive than in younger or female peers. The predictive power of PD was only slightly attenuated by adding measures of community deprivation, collective efficacy, or family socioeconomic status. Probands whose parents were divorced were more sensitive to the pathogenic effects of high PD environments. A robust positive interaction was also seen between genetic risk of DA (indexed by rates of DA in first-, second-, and third-degree relatives) and PD exposure. CONCLUSIONS AND RELEVANCE With sufficient data, PD can be measured in populations and strongly predicts DA. In a nationwide sample, risk factors at the level of the individual (genetic vulnerability), family (parental loss), and community (PD) contribute substantially to risk of DA. Individuals at elevated DA risk because of parental divorce or high genetic liability are more sensitive to the pathogenic effects of PD. Although the effect of our PD measure on DA liability cannot be explained by standard measures of community or family risk, we cannot, with available data, discriminate definitively between the effect of true peer effects and other unmeasured risk factors. PMID:24576925

Peer deviance, parental divorce, and genetic risk in the prediction of drug abuse in a nationwide Swedish sample: evidence of environment-environment and gene-environment interaction.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Sundquist, Kristina; Sundquist, Jan

2014-04-01

Peer deviance (PD) strongly predicts externalizing psychopathologic conditions but has not been previously assessable in population cohorts. We sought to develop such an index of PD and to clarify its effects on risk of drug abuse (DA). To examine how strongly PD increases the risk of DA and whether this community-level liability indicator interacts with key DA risk factors at the individual and family levels. Studies of future DA registration in 1,401,698 Swedish probands born from January 1, 1970, through December 31, 1985, and their adolescent peers in approximately 9200 small community areas. Peer deviance was defined as the proportion of individuals born within 5 years of the proband living in the same small community when the proband was 15 years old who eventually were registered for DA. Drug abuse recorded in medical, legal, or pharmacy registry records. Peer deviance was associated with future DA in the proband, with rates of DA in older and male peers more strongly predictive than in younger or female peers. The predictive power of PD was only slightly attenuated by adding measures of community deprivation, collective efficacy, or family socioeconomic status. Probands whose parents were divorced were more sensitive to the pathogenic effects of high PD environments. A robust positive interaction was also seen between genetic risk of DA (indexed by rates of DA in first-, second-, and third-degree relatives) and PD exposure. With sufficient data, PD can be measured in populations and strongly predicts DA. In a nationwide sample, risk factors at the level of the individual (genetic vulnerability), family (parental loss), and community (PD) contribute substantially to risk of DA. Individuals at elevated DA risk because of parental divorce or high genetic liability are more sensitive to the pathogenic effects of PD. Although the effect of our PD measure on DA liability cannot be explained by standard measures of community or family risk, we cannot, with available data, discriminate definitively between the effect of true peer effects and other unmeasured risk factors.

Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency: Twelve-Month Results of the DEFINITIVE AR Study.

PubMed

Zeller, Thomas; Langhoff, Ralf; Rocha-Singh, Krishna J; Jaff, Michael R; Blessing, Erwin; Amann-Vesti, Beatrice; Krzanowski, Marek; Peeters, Patrick; Scheinert, Dierk; Torsello, Giovanni; Sixt, Sebastian; Tepe, Gunnar

2017-09-01

Studies assessing drug-coated balloons (DCB) for the treatment of femoropopliteal artery disease are encouraging. However, challenging lesions, such as severely calcified, remain difficult to treat with DCB alone. Vessel preparation with directional atherectomy (DA) potentially improves outcomes of DCB. DEFINITIVE AR study (Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency-A Pilot Study of Anti-Restenosis Treatment) was a multicenter randomized trial designed to estimate the effect of DA before DCB to facilitate the development of future end point-driven randomized studies. One hundred two patients with claudication or rest pain were randomly assigned 1:1 to DA+DCB (n=48) or DCB alone (n=54), and 19 additional patients with severely calcified lesions were treated with DA+DCB. Mean lesion length was 11.2±4.0 cm for DA+DCB and 9.7±4.1 cm for DCB ( P =0.05). Predilation rate was 16.7% for DA+DCB versus 74.1% for DCB; postdilation rate was 6.3% for DA+DCB versus 33.3% for DCB. Technical success was superior for DA+DCB (89.6% versus 64.2%; P =0.004). Overall bail-out stenting rate was 3.7%, and rate of flow-limiting dissections was 19% for DCB and 2% for DA+DCB ( P =0.01). One-year primary outcome of angiographic percent diameter stenosis was 33.6±17.7% for DA+DCB versus 36.4±17.6% for DCB ( P =0.48), and clinically driven target lesion revascularization was 7.3% for DA+DCB and 8.0% for DCB ( P =0.90). Duplex ultrasound patency was 84.6% for DA+DCB, 81.3% for DCB ( P =0.78), and 68.8% for calcified lesions. Freedom from major adverse events at 1 year was 89.3% for DA+DCB and 90.0% for DCB ( P =0.86). DA+DCB treatment was effective and safe, but the study was not powered to show significant differences between the 2 methods of revascularization in 1-year follow-up. An adequately powered randomized trial is warranted. http://www.clinicaltrials.gov. Unique Identifier: NCT01366482. Copyright © 2017 The Author(s).

Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency

PubMed Central

Langhoff, Ralf; Rocha-Singh, Krishna J.; Jaff, Michael R.; Blessing, Erwin; Amann-Vesti, Beatrice; Krzanowski, Marek; Peeters, Patrick; Scheinert, Dierk; Torsello, Giovanni; Sixt, Sebastian; Tepe, Gunnar

2017-01-01

Background— Studies assessing drug-coated balloons (DCB) for the treatment of femoropopliteal artery disease are encouraging. However, challenging lesions, such as severely calcified, remain difficult to treat with DCB alone. Vessel preparation with directional atherectomy (DA) potentially improves outcomes of DCB. Methods and Results— DEFINITIVE AR study (Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency—A Pilot Study of Anti-Restenosis Treatment) was a multicenter randomized trial designed to estimate the effect of DA before DCB to facilitate the development of future end point-driven randomized studies. One hundred two patients with claudication or rest pain were randomly assigned 1:1 to DA+DCB (n=48) or DCB alone (n=54), and 19 additional patients with severely calcified lesions were treated with DA+DCB. Mean lesion length was 11.2±4.0 cm for DA+DCB and 9.7±4.1 cm for DCB (P=0.05). Predilation rate was 16.7% for DA+DCB versus 74.1% for DCB; postdilation rate was 6.3% for DA+DCB versus 33.3% for DCB. Technical success was superior for DA+DCB (89.6% versus 64.2%; P=0.004). Overall bail-out stenting rate was 3.7%, and rate of flow-limiting dissections was 19% for DCB and 2% for DA+DCB (P=0.01). One-year primary outcome of angiographic percent diameter stenosis was 33.6±17.7% for DA+DCB versus 36.4±17.6% for DCB (P=0.48), and clinically driven target lesion revascularization was 7.3% for DA+DCB and 8.0% for DCB (P=0.90). Duplex ultrasound patency was 84.6% for DA+DCB, 81.3% for DCB (P=0.78), and 68.8% for calcified lesions. Freedom from major adverse events at 1 year was 89.3% for DA+DCB and 90.0% for DCB (P=0.86). Conclusions— DA+DCB treatment was effective and safe, but the study was not powered to show significant differences between the 2 methods of revascularization in 1-year follow-up. An adequately powered randomized trial is warranted. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique Identifier: NCT01366482. PMID:28916599

Sensitive determination of dopamine levels via surface-enhanced Raman scattering of Ag nanoparticle dimers.

PubMed

Yu, Xiantong; He, XiaoXiao; Yang, Taiqun; Zhao, Litao; Chen, Qichen; Zhang, Sanjun; Chen, Jinquan; Xu, Jianhua

2018-01-01

Dopamine (DA) is an important neurotransmitter in the hypothalamus and pituitary gland, which can produce a direct influence on mammals' emotions in midbrain. Additionally, the level of DA is highly related with some important neurologic diseases such as schizophrenia, Parkinson, and Huntington's diseases, etc. In light of the important roles that DA plays in the disease modulation, it is of considerable significance to develop a sensitive and reproducible approach for monitoring DA. The objective of this study was to develop an efficient approach to quantitatively monitor the level of DA using Ag nanoparticle (NP) dimers and enhanced Raman spectroscopy. Ag NP dimers were synthesized for the sensitive detection of DA via surface-enhanced Raman scattering (SERS). Citrate was used as both the capping agent of NPs and sensing agent to DA, which is self-assembled on the surface of Ag NP dimers by reacting with the surface carboxyl group to form a stable amide bond. To improve accuracy and precision, the multiplicative effects model for surface-enhanced Raman spectroscopy was utilized to analyze the SERS assays. A low limits of detection (LOD) of 20 pM and a wide linear response range from 30 pM to 300 nM were obtained for DA quantitative detection. The SERS enhancement factor was theoretically valued at approximately 10 7 by discrete dipole approximation. DA was self-assembled on the citrate capped surface of Ag NPs dimers through the amide bond. The adsorption energy was estimated to be 256 KJ/mol using the Langmuir isotherm model. The density functional theory was used to simulate the spectral characteristics of SERS during the adsorption of DA on the surface of the Ag dimers. Furthermore, to improve the accuracy and precision of quantitative analysis of SERS assays with a multiplicative effects model for surface-enhanced Raman spectroscopy. A LOD of 20 pM DA-level was obtained, and the linear response ranged from 30 pM to 300 nM for quantitative DA detection. The absolute relative percentage error was 4.22% between the real and predicted DA concentrations. This detection scheme is expected to have good applications in the prevention and diagnosis of certain diseases caused by disorders in the DA level.

Sensitive determination of dopamine levels via surface-enhanced Raman scattering of Ag nanoparticle dimers

PubMed Central

Yu, Xiantong; He, XiaoXiao; Yang, Taiqun; Zhao, Litao; Chen, Qichen; Zhang, Sanjun; Chen, Jinquan; Xu, Jianhua

2018-01-01

Background Dopamine (DA) is an important neurotransmitter in the hypothalamus and pituitary gland, which can produce a direct influence on mammals’ emotions in midbrain. Additionally, the level of DA is highly related with some important neurologic diseases such as schizophrenia, Parkinson, and Huntington’s diseases, etc. In light of the important roles that DA plays in the disease modulation, it is of considerable significance to develop a sensitive and reproducible approach for monitoring DA. Purpose The objective of this study was to develop an efficient approach to quantitatively monitor the level of DA using Ag nanoparticle (NP) dimers and enhanced Raman spectroscopy. Methods Ag NP dimers were synthesized for the sensitive detection of DA via surface-enhanced Raman scattering (SERS). Citrate was used as both the capping agent of NPs and sensing agent to DA, which is self-assembled on the surface of Ag NP dimers by reacting with the surface carboxyl group to form a stable amide bond. To improve accuracy and precision, the multiplicative effects model for surface-enhanced Raman spectroscopy was utilized to analyze the SERS assays. Results A low limits of detection (LOD) of 20 pM and a wide linear response range from 30 pM to 300 nM were obtained for DA quantitative detection. The SERS enhancement factor was theoretically valued at approximately 107 by discrete dipole approximation. DA was self-assembled on the citrate capped surface of Ag NPs dimers through the amide bond. The adsorption energy was estimated to be 256 KJ/mol using the Langmuir isotherm model. The density functional theory was used to simulate the spectral characteristics of SERS during the adsorption of DA on the surface of the Ag dimers. Furthermore, to improve the accuracy and precision of quantitative analysis of SERS assays with a multiplicative effects model for surface-enhanced Raman spectroscopy. Conclusion A LOD of 20 pM DA-level was obtained, and the linear response ranged from 30 pM to 300 nM for quantitative DA detection. The absolute relative percentage error was 4.22% between the real and predicted DA concentrations. This detection scheme is expected to have good applications in the prevention and diagnosis of certain diseases caused by disorders in the DA level. PMID:29713165

Distinctive Modulation of Dopamine Release in the Nucleus Accumbens Shell Mediated by Dopamine and Acetylcholine Receptors.

PubMed

Shin, Jung Hoon; Adrover, Martin F; Alvarez, Veronica A

2017-11-15

Nucleus accumbens (NAc) shell shows unique dopamine (DA) signals in vivo and plays a unique role in DA-dependent behaviors such as reward-motivated learning and the response to drugs of abuse. A disynaptic mechanism for DA release was reported and shown to require synchronized firing of cholinergic interneurons (CINs) and activation of nicotinic acetylcholine (ACh) receptors (nAChRs) in DA neuron (DAN) axons. The properties of this disynaptic mechanism of DA transmission are not well understood in the NAc shell. In this study, in vitro fast-scan cyclic voltammetry was used to examine the modulation of DA transmission evoked by CINs firing in the shell of mice and compared with other striatal regions. We found that DA signals in the shell displayed significant degree of summation in response to train stimulation of CINs, contrary to core and dorsal striatum. The summation was amplified by a D2-like receptor antagonist and experiments with mice with targeted deletion of D2 receptors to DANs or CINs revealed that D2 receptors in CINs mediate a fast inhibition observed within 100 ms of the first pulse, whereas D2 autoreceptors in DAN terminals are engaged in a slower inhibition that peaks at ∼500 ms. ACh also contributes to the use-dependent inhibition of DA release through muscarinic receptors only in the shell, where higher activity of acetylcholinesterase minimizes nAChR desensitization and promotes summation. These findings show that DA signals are modulated differentially by endogenous DA and ACh in the shell, which may underlie the unique features of shell DA signals in vivo SIGNIFICANCE STATEMENT The present study reports that dopamine (DA) release evoked by activation of cholinergic interneurons displays a high degree of summation in the shell and shows unique modulation by endogenous DA and acetylcholine. Desensitization of nicotinic receptors, which is a prevailing mechanism for use-dependent inhibition in the nucleus accumbens core and dorsal striatum, is also minimal in the shell in part due to elevated acetylcholinesterase activity. This distinctive modulation of DA transmission in the shell may have functional implications in the acquisition of reward-motivated behaviors and reward seeking. Copyright © 2017 the authors 0270-6474/17/3711166-15$15.00/0.

Characterization of Optically and Electrically Evoked Dopamine Release in Striatal Slices from Digenic Knock-in Mice with DAT-Driven Expression of Channelrhodopsin

PubMed Central

2017-01-01

Fast-scan cyclic voltammetry (FCV) is an established method to monitor increases in extracellular dopamine (DA) concentration ([DA]o) in the striatum, which is densely innervated by DA axons. Ex vivo brain slice preparations provide an opportunity to identify endogenous modulators of DA release. For these experiments, local electrical stimulation is often used to elicit release of DA, as well as other transmitters, in the striatal microcircuitry; changes in evoked increases in [DA]o after application of a pharmacological agent (e.g., a receptor antagonist) indicate a regulatory role for the transmitter system interrogated. Optogenetic methods that allow specific stimulation of DA axons provide a complementary, bottom-up approach for elucidating factors that regulate DA release. To this end, we have characterized DA release evoked by local electrical and optical stimulation in striatal slices from mice that genetically express a variant of channelrhodopsin-2 (ChR2). Evoked increases in [DA]o in the dorsal and ventral striatum (dStr and vStr) were examined in a cross of a Cre-dependent ChR2 line (“Ai32” mice) with a DAT::Cre mouse line. In dStr, repeated optical pulse-train stimulation at the same recording site resulted in rundown of evoked [DA]o using heterozygous mice, which contrasted with the stability seen with electrical stimulation. Similar rundown was seen in the presence of a nicotinic acetylcholine receptor (nAChR) antagonist, implicating the absence of concurrent nAChR activation in DA release instability in slices. Rundown with optical stimulation in dStr could be circumvented by recording from a population of sites, each stimulated only once. Same-site rundown was less pronounced with single-pulse stimulation, and a stable baseline could be attained. In vStr, stable optically evoked increases in [DA]o at single sites could be achieved using heterozygous mice, although with relatively low peak [DA]o. Low release could be overcome by using mice with a second copy of the Ai32 allele, which doubled ChR2 expression. The characteristics reported here should help future practitioners decide which Ai32;DAT::Cre genotype and recording protocol is optimal for the striatal subregion to be examined. PMID:28177213

Differential effects of pyrethroid insecticides on extracellular dopamine in the striatum of freely moving rats

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

Mubarak Hossain, Muhammad; Suzuki, Tadahiko; United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193

2006-11-15

In order to obtain a more complete understanding of pyrethroid neurotoxicity, effects of the pyrethroid insecticides, allethrin (type I), cyhalothrin (type II) and deltamethrin (type II) on extracellular levels of dopamine (DA) and its metabolites in the striatum of conscious rats were studied by in vivo microdialysis. Rats were treated i.p. with pyrethroids or vehicle. Allethrin had a dual effect on DA release. The increase in the extracellular level of striatal DA by 10 mg/kg allethrin reached a maximum of 178% of baseline but 20 and 60 mg/kg inhibited DA release to 63% and 52% of baseline with a peakmore » effect at 60-80 min after injection. Cyhalothrin 10, 20 and 60 mg/kg inhibited DA release to 65%, 56% and 45% of basal release, respectively, with a peak time of inhibition 40-80 min past injection. Deltamethrin (10 and 20 mg/kg) increased DA release to maximum of 187% and 252% of basal release whereas 60 mg/kg first reduced the efflux for 40 min to 50% of basal release and then increased the efflux to a maximum of 344% of basal release with a peak time of 120 min. Local infusion of 1 {mu}M tetrodotoxin, a Na{sup +} blocker through the dialysis probe completely prevented the effect of allethrin (10 and 60 mg/kg), cyhalothrin (60 mg/kg) and deltamethrin (20 mg/kg) on DA release but only partially blocked the effects of 60 mg/kg deltamethrin. The effect of deltamethrin (60 mg/kg) on DA release was completely prevented by local infusion of 10 {mu}M nimodipine, an L-type Ca{sup ++} channel blocker. All three pyrethroids did not alter the extracellular levels of DOPAC, 3-MT and HVA except that 20 and 60 mg/kg of allethrin and cyhalothrin increased 3-MT levels. Effect of the pyrethroids on synaptosomal DA uptake was also examined. The DA uptake was decreased in rats exposed to 60 mg/kg of allethrin and cyhalothrin but was increased in rats exposed to 60 mg/kg of deltamethrin. Our results demonstrate that striatal DA release and DA uptake are differentially affected by type I and the two type II pyrethroids indicating that dopaminergic circuitry, striatal DA in particular, may be a pyrethroid target and that pyrethroids may be acting on striatal DA by multiple mechanisms.« less

Reproducibility of quantitative measures of binding potential in rat striatum: A test re-test study using DTBZ dynamic PET studies

NASA Astrophysics Data System (ADS)

Avendaño-Estrada, A.; Lara-Camacho, V. M.; Ávila-García, M. C.; Ávila-Rodríguez, M. A.

2014-11-01

There is great interest in the study of dopamine (DA) pathways due to the increasing number of patients with illnesses related to the dopaminergic system and molecular imaging based in Positron Emission Tomography (PET) has been proven helpful for this task. Among the different radiopharmaceuticals available to study DA interaction, [11C ]Dihydrotetrabenazine (DTBZ) has a high affinity for the vesicular monoamine transporter type 2 (VMAT2) and its binding potential (BP) is a marker of DA terminal integrity. This paper reports on the intersubject reproducibility of BP measurements in rat striatum with [11C]DTBZ using the Logańs method.

Reproducibility of quantitative measures of binding potential in rat striatum: A test re-test study using DTBZ dynamic PET studies

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

Avendaño-Estrada, A., E-mail: avilarod@uwalumni.com; Lara-Camacho, V. M., E-mail: avilarod@uwalumni.com; Ávila-García, M. C., E-mail: avilarod@uwalumni.com

2014-11-07

There is great interest in the study of dopamine (DA) pathways due to the increasing number of patients with illnesses related to the dopaminergic system and molecular imaging based in Positron Emission Tomography (PET) has been proven helpful for this task. Among the different radiopharmaceuticals available to study DA interaction, [{sup 11}C]Dihydrotetrabenazine (DTBZ) has a high affinity for the vesicular monoamine transporter type 2 (VMAT2) and its binding potential (BP) is a marker of DA terminal integrity. This paper reports on the intersubject reproducibility of BP measurements in rat striatum with [11C]DTBZ using the Logańs method.

Complete nucleotide sequence of clematis chlorotic mottle virus, a new member of the family Tombusviridae.

PubMed

McLaughlin, Margaret; Lockhart, Ben; Jordan, Ramon; Denton, Geoff; Mollov, Dimitre

2017-05-01

Clematis chlorotic mottle virus (ClCMV) is a previously undescribed virus associated with symptoms of yellow mottling and veining, chlorotic ring spots, line pattern mosaics, and flower distortion and discoloration on ornamental Clematis. The ClCMV genome is 3,880 nt in length with five open reading frames (ORFs) encoding a 27-kDa protein (ORF 1), an 87-kDa replicase protein (ORF 2), two centrally located movement proteins (ORF 3 and 4), and a 37-kDa capsid protein (ORF 5). Based on morphological, genomic, and phylogenetic analysis, ClCMV is predicted to be a member of the genus Pelarspovirus in the family Tombusviridae.

Phosphatidylcholine Coatings Deliver Local Antimicrobials and Reduce Infection in a Murine Model: A Preliminary Study.

PubMed

Harris, Michael A; Beenken, Karen E; Smeltzer, Mark S; Haggard, Warren O; Jennings, J Amber

2017-07-01

Phosphatidylcholine coatings have been shown to elute antibiotics for several days. A recently developed biofilm inhibitor, cis-2-decenoic acid (C2DA), has been shown to exhibit synergistic activity with several common antibiotics. This study aims to evaluate the effectiveness of C2DA and amikacin dual drug delivery from a phosphatidylcholine coating. (1) What are the in vitro elution profiles of amikacin and C2DA from phosphatidylcholine-coated coupons in incubated phosphate-buffered saline? (2) Does the presence of C2DA in eluate samples lower the amount of amikacin needed for bacterial inhibition in overnight bacterial turbidity assays? (3) Does addition of amikacin and C2DA result in decreased colony-forming units (CFUs) on wire implants and bone when compared with phosphatidylcholine coatings alone in a mouse model of periprosthetic joint infection? Effects of loading concentrations were assessed during 7-day in vitro elution studies for coatings containing all mixtures of 0%, 5%, 15%, and 25% wt of amikacin and C2DA (n = 4) through quantitative high-performance liquid chromatography concentration determination and plotting concentration eluted over time. Antimicrobial activity was assessed by overnight turbidity testing of elution study samples against Staphylococcus aureus or Pseudomonas aeruginosa. In vivo efficacy was assessed using phosphatidylcholine-coated wire implants in a murine (mouse) model of infection (n = 3). Wire implants were coated with phosphatidylcholine containing no antimicrobials, amikacin alone, C2DA alone, or amikacin and C2DA and then inserted into the intramedullary femur of each mouse and inoculated with S aureus. The number of viable bacterial colonies on the implant surface and in the surrounding bone was determined after 1 week with the goal of achieving complete bacterial clearance. Total viable CFU count and proportion of samples achieving complete clearance were compared between groups. Elution samples showed a burst response of amikacin and C2DA for 1 to 2 days with C2DA release continuing at low levels through Day 4. All tested eluate samples inhibited P aeruginosa. Samples from coatings containing 25% amikacin or 15% amikacin and any amount of C2DA were able to inhibit S aureus formation, but all coatings with 5% amikacin or 15% amikacin but no C2DA were not inhibitory. All in vivo treatment groups achieved complete bacterial clearance on the wire implant, and the C2DA alone and amikacin alone coatings cleared all CFUs in bone (pin: phosphatidylcholine only one of three; amikacin three of three, C2DA three of three, amikacin + C2DA three of three, p = 0.04 [Fisher's exact test]; bone: coating only: zero of three; amikacin: three of three; C2DA; three of three; C2DA + amikacin: one of three; p = 0.03 [Fisher's exact test]). Phosphatidylcholine coatings elute antimicrobials in vitro under infinite sink conditions for up to 4 days in phosphate-buffered saline and were able to reduce bacterial colonies in a preliminary in vivo model. Turbidity testing with eluate samples containing varying amounts of C2DA and amikacin agrees with previous studies showing synergy between them. Used as an adjunctive to systemic therapy, C2DA-loaded phosphatidylcholine coatings have potential value as a prophylactic infection prevention measure. Future studies may include different antibiotics, animal studies with larger sample sizes and more controls, and advanced coating delivery methods.

Domain organization of p130, PLC-related catalytically inactive protein, and structural basis for the lack of enzyme activity.

PubMed

Kanematsu, T; Yoshimura, K; Hidaka, K; Takeuchi, H; Katan, M; Hirata, M

2000-05-01

The 130-kDa protein (p130) was isolated as a novel inositol 1,4, 5-trisphosphate [Ins(1,4,5)P3]-binding protein similar to phospholipase C-delta1 (PLC-delta1), but lacking catalytic activity [Kanematsu, T., Takeya, H., Watanabe, Y., Ozaki, S., Yoshida, M., Koga, T., Iwanaga, S. & Hirata, M. (1992) J. Biol. Chem. 267, 6518-6525; Kanematsu, T., Misumi, Y., Watanabe, Y., Ozaki, S., Koga, T., Iwanaga, S., Ikehara, Y. & Hirata, M. (1996) Biochem. J. 313, 319-325]. To test experimentally the domain organization of p130 and structural basis for lack of PLC activity, we subjected p130 to limited proteolysis and also constructed a number of chimeras with PLC-delta1. Trypsin treatment of p130 produced four major polypeptides with molecular masses of 86 kDa, 55 kDa, 33 kDa and 25 kDa. Two polypeptides of 86 kDa and 55 kDa started at Lys93 and were calculated to end at Arg851 and Arg568, respectively. Using the same approach, it has been found that the polypeptides of 33 kDa and 25 kDa are likely to correspond to regions between Val569 and Arg851 and Lys869 and Leu1096, respectively. All the proteolytic sites were in interconnecting regions between the predicted domains, therefore supporting domain organization based on sequence similarity to PLC-delta1 and demonstrating that all domains of p130, including the unique region at the C-terminus, are stable, tightly folded structures. p130 truncated at either or both the N-terminus (94 amino acids) and C-terminus (851-1096 amino acids) expressed in COS-1 cells showed no catalytic activity, indicating that p130 has intrinsically no PLC activity. A number of chimeric molecules between p130 and PLC-delta1 were constructed and assayed for PLC activity. It was shown that structural differences in interdomain interactions exist between the two proteins, as only some domains of p130 could replace the corresponding structures in PLC-delta1 to form a functional enzyme. These results suggest that p130 and the related proteins could represent a new protein family that may play some distinct role in cells due to the capability of binding Ins(1,4,5)P3 but the lack of catalytic activity.

Detecção da fase impulsiva de uma explosão solar gigante até 405 GHz

NASA Astrophysics Data System (ADS)

Raulin, J.-P.; Makhmutov, V.; Kaufmann, P.; Pacini, A. A.; Luethi, T.; Hudson, H. S.; Gary, D. E.; Yoshimori, M.

2003-08-01

A explosão ocorrida no dia 25/08/2001 foi uma das mais intensas do presente ciclo solar em ondas de rádio de altas frequências. Foram medidas em ondas milimétricas e submilimétricas, aproximadamente, 105 e vários milhares de unidades de fluxo solar, respectivamente. Apresentamos um estudo deste evento em múltiplas frequências, desde microondas (1GHz), até ondas submilimétricas (405 GHz) detectadas pelo Telescópio Solar para ondas Submilimétricas (SST). Esta base de dados foi complementada utilizando-se o experimento Yohkoh, incluindo a emissão em raios-X duros e raios-g (até 100 MeV), e imagens em raios-X moles da região ativa envolvida. Enfocamos e discutimos principalmente os seguintes aspectos da fase impulsiva do evento: (i) as implicações deduzidas do espectro eletromagnético, obtido pela primeira vez até 405 GHz; (ii) a dinâmica da região ativa. Os resultados mostram que para explicar o espectro rádio observado, são necessários entre 3.5×1037 e 1.5×1039 elétrons acelerados acima de 20 keV em uma região de campo magnético entre 300 e 800 Gauss. A estimativa do fluxo de fótons que seria produzido por estes elétrons, mostra que grande parte deles não precipitou na baixa atmosfera. A evolução temporal da emissão em raios-X moles revela que a configuração magnética da região ativa foi muito dinâmica durante a fase impulsiva da explosão. Em particular, mostramos que a produção dos elétrons altamente energéticos foi iniciada junto com a aparição, na baixa coroa solar, de um novo sistema compacto de estruturas magnéticas. Este fato sugere que os locais de aceleração estão localizados na baixa atmosfera do Sol, como resultado da interação entre o novo sistema compacto e o campo magnético ambiente da região ativa.

Construção de um catálogo de aglomerados abertos para estudo da dinâmica da estrutura espiral da Galáxia

NASA Astrophysics Data System (ADS)

Carlos, I. M.; Lépine, J. R. D.

2003-08-01

Os aglomerados abertos são objetos de grande valor para o estudo da dinâmica da Galáxia devido esses objetos terem uma faixa de idade relativamente ampla. O trabalho visa estudar a dinâmica da estrutura espiral da Galáxia principalmente através do uso desses aglomerados, uma vez que o estudo da cinemática desses objetos é fundamental para esse objetivo. Nosso grupo trabalha no sentido de construir uma base de dados de aglomerados abertos contendo coordenadas, distância, idade, movimentos próprios e velocidades radiais e já disponibiliza uma nova versão do catálogo de aglomerados abertos o qual é uma compilação de edições anteriores, principalmente Lynga (1987), Mermilliod (1995) e ESO-B (Lauberts 1982). Nossa amostra possui cerca de 1630 aglomerados, mas nem todos os parâmetros acima citados foram determinados em sua totalidade. Para determinarmos esses parâmetros, derivamos as cores intrínsecas das estrelas membro de cada aglomerado a partir de seus tipos espectrais (busca feita no SIMBAD) obtendo assim o excesso de cor individual. A distribuição dos excessos de cor foi então utilizada para derivarmos o avermelhamento médio para cada aglomerado. De maneira similar, os tipos espectrais foram usados para estimar as magnitudes absolutas, e com as magnitudes absolutas e aparentes determinamos a respectiva distribuição do módulo de distância e finalmente a distância. Para determinar as idades foram confeccionados os diagramas cor-magnitude das estrelas de cada aglomerado onde foram superpostas a Seqüência Principal de Idade Zero (ZAMS). Superpomos a ZAMS de Schmidt-Kaler e isócronas de composição solar. Essas isócronas foram usadas para determinação das idades dos aglomerados. Uma vez que não temos ainda resultados finais, apresentamos então alguns diagramas cor-magnitude os quais foram usados para determinação, principalmente, da distância e idade dos aglomerados.

Health, development and innovation: a contribution of the critical theory of technology to the discussion.

PubMed

Souza, Luis Eugenio Portela Fernandes de

2016-11-03

The relationships between health and socioeconomic development are diverse. These relationships find in the health economic complex a privileged ground for expression. The importance of health technologies increased exponentially since the middle of the 20th century, affecting health systems in terms of both, quality of care and economic aspects. In fact, the predominant model of care is based on fragmented, symptomatic therapy practices that encourages the use of products and services and promotes a passive participation of users rather than humanization of care. Overcoming this model requires changes in the health technology standards which, in turn, require changes in the technology standard of society. The critical theory of technology helps to understand the evolution of the industrial civilization. It enriches the discussion by suggesting the health economic complex be more sensibly adjusted to the requirements of comprehensive health care, and to inclusive and sustainable development. Resumo: As relações entre a saúde e o desenvolvimento socioeconômico são múltiplas. Essas relações têm o complexo econômico da saúde como o espaço privilegiado de sua expressão. A importância das tecnologias de saúde aumentou exponencialmente desde meados do século XX, com efeitos sobre os sistemas de saúde, tanto em qualidade da atenção, quanto em aspectos econômicos. Na realidade, predomina um modelo de atenção caracterizado por práticas fragmentadas, que enfatizam tratamentos sintomáticos, estimulam o consumismo de produtos e serviços e promovem, ao invés da humanização, uma participação passiva dos usuários. A superação desse modelo passa pela mudança do padrão tecnológico da saúde, que, por sua vez, exige a transformação do padrão tecnológico da sociedade. A teoria crítica da tecnologia ajuda a compreender a evolução da civilização industrial. Enriquece o debate, sugerindo uma conformação do complexo econômico da saúde mais sensível às exigências da atenção integral à saúde e do desenvolvimento inclusivo e sustentável.

Involvement of Lipocalin-like CghA in Decalin-Forming Stereoselective Intramolecular [4+2] Cycloaddition

PubMed Central

Sato, Michio; Yagishita, Fumitoshi; Mino, Takashi; Uchiyama, Nahoko; Patel, Ashay; Chooi, Yit-Heng; Goda, Yukihiro; Xu, Wei; Noguchi, Hiroshi; Yamamoto, Tsuyoshi; Hotta, Kinya; Houk, Kendall N.; Tang, Yi

2016-01-01

Understanding enzymatic Diels—Alder (DA) reactions that can form complex natural product scaffold is of considerable interest. Sch 210972 1, a potential anti-HIV fungal natural product, contains a decalin core that is proposed to form via a DA reaction. We identified the gene cluster responsible for the biosynthesis of 1 and heterologously reconstituted the biosynthetic pathway in Aspergillus nidulans to characterize the enzymes involved. Most notably, deletion of cghA resulted in a loss of stereoselective decalin core formation, yielding both an endo 1 and a diastereomeric exo adducts of the proposed DA reaction. Complementation with cghA restored the sole formation of 1. Density functional theory computation of the proposed DA reaction provided a plausible explanation of the observed pattern of product formation. Based on our study, we propose that lipocalin-like CghA is responsible for the stereoselective intramolecular [4+2] cycloaddition that forms the decalin core of 1. PMID:26360642

The ATLAS PanDA Pilot in Operation

NASA Astrophysics Data System (ADS)

Nilsson, P.; Caballero, J.; De, K.; Maeno, T.; Stradling, A.; Wenaus, T.; ATLAS Collaboration

2011-12-01

The Production and Distributed Analysis system (PanDA) [1-2] was designed to meet ATLAS [3] requirements for a data-driven workload management system capable of operating at LHC data processing scale. Submitted jobs are executed on worker nodes by pilot jobs sent to the grid sites by pilot factories. This paper provides an overview of the PanDA pilot [4] system and presents major features added in light of recent operational experience, including multi-job processing, advanced job recovery for jobs with output storage failures, gLExec [5-6] based identity switching from the generic pilot to the actual user, and other security measures. The PanDA system serves all ATLAS distributed processing and is the primary system for distributed analysis; it is currently used at over 100 sites worldwide. We analyze the performance of the pilot system in processing real LHC data on the OSG [7], EGI [8] and Nordugrid [9-10] infrastructures used by ATLAS, and describe plans for its evolution.

Mevalocidin: a novel, phloem mobile phytotoxin from Fusarium DA056446 and Rosellinia DA092917.

PubMed

Gerwick, B Clifford; Brewster, William K; Deboer, Gerrit J; Fields, Steve C; Graupner, Paul R; Hahn, Donald R; Pearce, Cedric J; Schmitzer, Paul R; Webster, Jeffery D

2013-02-01

A multiyear effort to identify new natural products was built on a hypothesis that both phytotoxins from plant pathogens and antimicrobial compounds might demonstrate herbicidal activity. The discovery of one such compound, mevalocidin, is described in the current report. Mevalocidin was discovered from static cultures of two unrelated fungal isolates designated Rosellinia DA092917 and Fusarium DA056446. The chemical structure was confirmed by independent synthesis. Mevalocidin demonstrated broad spectrum post-emergence activity on grasses and broadleaves and produced a unique set of visual symptoms on treated plants suggesting a novel mode of action. Mevalocidin was rapidly absorbed in a representative grass and broadleaf plant. Translocation occurred from the treated leaf to other plant parts including roots confirming phloem as well as xylem mobility. By 24 hr after application, over 20 % had been redistributed through-out the plant. Mevalocidin is a unique phytotoxin based on its chemistry, with the uncommon attribute of demonstrating both xylem and phloem mobility in grass and broadleaf plants.

The Value of Information from a GRACE-Enhanced Drought Severity Index

NASA Astrophysics Data System (ADS)

Kuwayama, Y.; Bernknopf, R.; Brookshire, D.; Macauley, M.; Zaitchik, B. F.; Rodell, M.; Vail, P.; Thompson, A.

2015-12-01

In this project, we develop a framework to estimate the economic value of information from the Gravity and Climate Experiment (GRACE) for drought monitoring and to understand how the GRACE Data Assimilation (GRACE-DA) system can inform decision making to improve regional economic outcomes. Specifically, we consider the potential societal value of further incorporating GRACE-DA information into the U.S. Drought Monitor mapmaking process. Research activities include (a) a literature review, (b) a series of listening sessions with experts and stakeholders, (c) the development of a conceptual economic framework based on a Bayesian updating procedure, and (d) an econometric analysis and retrospective case study to understand the GRACE-DA contribution to agricultural policy and production decisions. Taken together, the results from these research activities support our conclusion that GRACE-DA has the potential to lower the variance associated with our understanding of drought and that this improved understanding has the potential to change policy decisions that lead to tangible societal benefits.

Inkjet-compatible single-component polydiacetylene precursors for thermochromic paper sensors.

PubMed

Yoon, Bora; Shin, Hyora; Kang, Eun-Mi; Cho, Dae Won; Shin, Kayeong; Chung, Hoeil; Lee, Chan Woo; Kim, Jong-Man

2013-06-12

Inkjet-printable diacetylene (DA) supramolecules, which can be dispersed in water without using additional surfactants, have been developed. The supramolecules are generated from DA monomers that contain bisurea groups, which are capable of forming hydrogen-bonding networks, and hydrophilic oligoethylene oxide moieties. Because of suitable size distribution and stability characteristics, the single DA component ink can be readily transferred to paper substrates by utilizing a common office inkjet printer. UV irradiation of the DA-printed paper results in generation of blue-colored polydiacetylene (PDA) images, which show reversible thermochromic transitions in specific temperature ranges. Inkjet-printed PDAs, in the format of a two-dimensional (2D) quick response (QR) code on a real parking ticket, serve as a dual anticounterfeiting system that combines easy decoding of the QR code and colorimetric PDA reversibility for validating the authenticity of the tickets. This single-component ink system has great potential for use in paper-based devices, temperature sensors, and anticounterfeiting barcodes.

THE SPECTRAL EVOLUTION OF CONVECTIVE MIXING WHITE DWARFS, THE NON-DA GAP, AND WHITE DWARF COSMOCHRONOLOGY

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

Chen, Eugene Y.; Hansen, Brad M. S., E-mail: eyc@mail.utexas.edu, E-mail: hansen@astro.ucla.edu

The spectral distribution of field white dwarfs shows a feature called the 'non-DA gap'. As defined by Bergeron et al., this is a temperature range (5100-6100 K) where relatively few non-DA stars are found, even though such stars are abundant on either side of the gap. It is usually viewed as an indication that a significant fraction of white dwarfs switch their atmospheric compositions back and forth between hydrogen-rich and helium-rich as they cool. In this Letter, we present a Monte Carlo model of the Galactic disk white dwarf population, based on the spectral evolution model of Chen and Hansen.more » We find that the non-DA gap emerges naturally, even though our model only allows white dwarf atmospheres to evolve monotonically from hydrogen-rich to helium-rich through convective mixing. We conclude by discussing the effects of convective mixing on the white dwarf luminosity function and the use thereof for Cosmochronology.« less

32 CFR 516.25 - DA Form 4.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true DA Form 4. 516.25 Section 516.25 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Reporting Legal Proceedings to HQDA § 516.25 DA Form 4. (a) General. The DA Form 4 (See figure C-2...

32 CFR 516.43 - Release of Army and other agency records.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Preservation of originals. To preserve the integrity of DA records, DA personnel will submit properly... otherwise by Litigation Division. (See 28 U.S.C. 1733.) (b) Authentication of copies. Copies of DA records approved for release can be authenticated for introduction in evidence by use of DA Form 4. (See § 516.25...

32 CFR 536.32 - Transfer of claims among armed services branches.

Code of Federal Regulations, 2010 CFR

2010-07-01

... take all actions on the claim. Where the DA is the lead agency, any final action will include other agencies. Similarly, where another agency is the lead agency, that agency will be requested to include DA... another agency has taken denial action on a claim that involves the DA, without informing the DA, and in...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2014 CFR

2014-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2010 CFR

2010-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2011 CFR

2011-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2013 CFR

2013-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2012 CFR

2012-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

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Specificity and impact of adrenergic projections to the midbrain dopamine system

PubMed Central

Mejias-Aponte, Carlos A.

2016-01-01

Dopamine (DA) is a neuromodulator that regulates different brain circuits involved in cognitive functions, motor coordination, and emotions. Dysregulation of DA is associated with many neurological and psychiatric disorders such as Parkinson’s disease and substance abuse. Several lines of research have shown that the midbrain DA system is regulated by the central adrenergic system. This review focuses on adrenergic interactions with midbrain DA neurons. It discusses the current neuroanatomy including source of adrenergic innervation, type of synapses, and adrenoceptors expression. It also discusses adrenergic regulation of DA cell activity and neurotransmitter release. Finally, it reviews several neurological and psychiatric disorders where changes in adrenergic system are associated with dysregulation of the midbrain DA system. PMID:26820641

Preparation and characterization of novel nanocomposites of inorganic/polysaccharide type =

NASA Astrophysics Data System (ADS)

Oliveira, Fabiane Costa

O uso de polimeros naturais no ambito da preparacao de nanocompositos nao tem sido tao amplamente estudado quando comparado com os polimeros sinteticos. Assim, esta tese tem como objectivo estudar metodologias para a preparacao de novos materiais nanocompositos sob a forma de dispersoes e filmes utilizando polissacarideos como matriz. A tese esta dividida em cinco capitulos sendo o ultimo capitulo dedicado as conclusoes gerais e a sugestoes para trabalhos futuros. Inicialmente e apresentada uma breve revisao bibliografica sobre os principais temas colocando esta tese em contexto. Consideracoes sobre o uso de polimeros naturais e a sua combinacao com a utilizacao de nanoparticulas inorganicas para a fabricacao de novos bionanocomposites sao descritas e os objectivos e outline da tese sao tambem apresentados. No segundo capitulo, a preparacao de particulas de silica puras ou modificadas bem como a sua caracterizacao por FTIR, SEM, TEM, TGA, DLS (tamanho e potencial zeta) e medicoes de angulo de contacto sao discutidas. De modo a melhorar a compatibilidade da silica com os polissacarideos, as particulas SiO2 foram modificados com dois compostos do tipo organosilano: 3- metacril-oxipropil-trimetoxissilano (MPS) e 3-aminopropil-trimetoxissilano (APS). As particulas SiO2 MPS foram posteriormente encapsuladas com de poli(metacrilato de glicidilo) utilizando a tecnica de polimerizacao em emulsao. A utilizacao dos nanocompositos resultantes na preparacao de dispersoes de bionanocompositos nao foi bem sucedida e por esse motivo nao os estudos nao foram prosseguidos. O uso de SiO2 APS na preparacao de dispersoes bionanocomposite foi eficiente. No terceiro capitulo e apresentada uma revisao sobre dispersoes bionanocompositas e respectiva caracterizacao destacando aspectos fundamentais sobre reologia e microestrutura. Em seguida, e discutido o estudo sistematico realizado sobre o comportamento reologico de dispersoes de SiO2 utilizando tres polissacarideos distintos no que concerne a carga e as caracteristicas gelificantes: a goma de alfarroba (nao ionica), o quitosano (cationico) e a goma xantana (anionica) cujas propriedades reologicas sao amplamente conhecidas. Os estudos reologicos realizados sob diferentes condicoes demonstraram que a formacao de geis frageis e/ou bem estruturados depende do tamanho SiO2, da concentracao, do pH e da forca ionica. Estes estudos foram confirmados por analises microestruturais usando a microscopia electronica a baixas temperaturas (Cryo-SEM). No quarto capitulo, sao apresentados os estudos relativos a preparacao e caracterizacao de filmes bionanocompositos utilizando quitosano como matriz. Primeiramente e apresentada uma revisao sobre filmes de bionanocompositos e os aspectos fundamentais das tecnicas de caracterizacao utilizadas. A escolha do plasticizante e da sua concentracao sao discutidas com base nas propriedades de filmes de quitosano preparados. Em seguida, o efeito da concentracao de silica e dos metodos utilizados para a dispersar na matriz de polissacarideo, bem como o efeito da modificacao da superficie da silica e avaliado. As caracteristicas da superficie e as propriedades de barreira, mecanicas e termicas sao discutidas para cada conjunto de filmes preparados antes e apos a sua neutralizacao. Os resultados obtidos mostraram que a dispersao das cargas no plasticizante e posterior adicao a matriz polissacaridica resultaram apenas em pequenas melhorias ja que o problema da agregacao de silica nao foi ultrapassado. Por esse motivo foram preparados filmes com SiO2 APS os quais apresentaram propriedades melhores apesar da agregacao das particulas nao ter sido completamente impedida. Tal pode estar relacionado com o processo de secagem dos filmes. Finalmente, no capitulo 5, sao apresentadas as principais conclusoes obtidas e algumas sugestoes para trabalho futuro.

DeoxyArbutin: a novel reversible tyrosinase inhibitor with effective in vivo skin lightening potency.

PubMed

Boissy, Raymond E; Visscher, Marty; DeLong, Mitchell A

2005-08-01

Modulation of melanogenesis in the melanocytes can be achieved using chemicals that share structural homologies with the substrate tyrosine and as thus competitively inhibit the catalytic function of tyrosinase. We have developed a new tyrosinase inhibitor, deoxyArbutin (dA), based on this premise. DeoxyArbutin demonstrates effective inhibition of mushroom tyrosinase in vitro with a Ki that is 10-fold lower that hydroquinone (HQ) and 350-fold lower than arbutin. In a hairless, pigmented guinea pig model, dA demonstrated rapid and sustained skin lightening that was completely reversible within 8 weeks after halt in topical application. In contrast, HQ induced a short but unsustained skin lightening effect whereas kojic acid and arbutin exhibit no skin lightening effect. Results from a panel of safety tests supported the overall establishment of dA as an actionable molecule. In a human clinical trial, topical treatment of dA for 12 weeks resulted in a significant or slight reduction in overall skin lightness and improvement of solar lentigines in a population of light skin or dark skin individuals, respectively. These data demonstrate that dA has potential tyrosinase inhibitory activity that can result in skin lightening and may be used to ameliorate hyperpigmentary lesions.

Sensitive electrochemical sensors for simultaneous determination of ascorbic acid, dopamine, and uric acid based on Au@Pd-reduced graphene oxide nanocomposites.

PubMed

Jiang, Jingjing; Du, Xuezhong

2014-10-07

Sensitive electrochemical sensors were fabricated with reduced graphene oxide-supported Au@Pd (Au@Pd-RGO) nanocomposites by one-step synthesis for individual and simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA) with low detection limits and wide concentration ranges. From the Au@Pd-RGO-modified electrodes, well-separated oxidation peaks and enhanced peak currents of AA, DA, and UA were observed owing to the superior conductivity of RGO and the excellent catalytic activity of Au@Pd nanoparticles. For individual detection, the linear responses of AA, DA, and UA were in the concentration ranges of 0.1-1000, 0.01-100, and 0.02-500 μM with detection limits of 0.02, 0.002, and 0.005 μM (S/N = 3), respectively. For simultaneous detection by synchronous change of the concentrations of AA, DA, and UA, the linear response ranges were 1-800, 0.1-100, and 0.1-350 μM with detection limits of 0.28, 0.024, and 0.02 μM (S/N = 3), respectively. The fabricated sensors were further applied to the detection of AA, DA, and UA in urine samples. The Au@Pd-RGO nanocomposites have promising applications in highly sensitive and selective electrochemical sensing.

Single nucleotide editing without DNA cleavage using CRISPR/Cas9-deaminase in the sea urchin embryo.

PubMed

Shevidi, Saba; Uchida, Alicia; Schudrowitz, Natalie; Wessel, Gary M; Yajima, Mamiko

2017-12-01

A single base pair mutation in the genome can result in many congenital disorders in humans. The recent gene editing approach using CRISPR/Cas9 has rapidly become a powerful tool to replicate or repair such mutations in the genome. These approaches rely on cleaving DNA, while presenting unexpected risks. In this study, we demonstrate a modified CRISPR/Cas9 system fused to cytosine deaminase (Cas9-DA), which induces a single nucleotide conversion in the genome. Cas9-DA was introduced into sea urchin eggs with sgRNAs targeted for SpAlx1, SpDsh, or SpPks, each of which is critical for skeletogenesis, embryonic axis formation, or pigment formation, respectively. We found that both Cas9 and Cas9-DA edit the genome, and cause predicted phenotypic changes at a similar efficiency. Cas9, however, resulted in significant deletions in the genome centered on the gRNA target sequence, whereas Cas9-DA resulted in single or double nucleotide editing of C to T conversions within the gRNA target sequence. These results suggest that the Cas9-DA approach may be useful for manipulating gene activity with decreased risks of genomic aberrations. Developmental Dynamics 246:1036-1046, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The Settings, Pros and Cons of the New Surgical Robot da Vinci Xi System for Transoral Robotic Surgery (TORS): A Comparison With the Popular da Vinci Si System.

PubMed

Kim, Da Hee; Kim, Hwan; Kwak, Sanghyun; Baek, Kwangha; Na, Gina; Kim, Ji Hoon; Kim, Se Heon

2016-10-01

The da Vinci system (da Vinci Surgical System; Intuitive Surgical Inc.) has rapidly developed in several years from the S system to the Si system and now the Xi System. To investigate the surgical feasibility and to provide workflow guidance for the newly released system, we used the new da Vinci Xi system for transoral robotic surgery (TORS) on a cadaveric specimen. Bilateral supraglottic partial laryngectomy, hypopharyngectomy, lateral oropharyngectomy, and base of the tongue resection were serially performed in search of the optimal procedures with the new system. The new surgical robotic system has been upgraded in all respects. The telescope and camera were incorporated into one system, with a digital end-mounted camera. Overhead boom rotation allows multiquadrant access without axis limitation, the arms are now thinner and longer with grabbing movements for easy adjustments. The patient clearance button dramatically reduces external collisions. The new surgical robotic system has been optimized for improved anatomic access, with better-equipped appurtenances. This cadaveric study of TORS offers guidance on the best protocol for surgical workflow with the new Xi system leading to improvements in the functional results of TORS.