Science.gov

Sample records for enhanced attenuation categories

  1. When Does Fading Enhance Perceptual Category Learning?

    ERIC Educational Resources Information Center

    Pashler, Harold; Mozer, Michael C.

    2013-01-01

    Training that uses exaggerated versions of a stimulus discrimination (fading) has sometimes been found to enhance category learning, mostly in studies involving animals and impaired populations. However, little is known about whether and when fading facilitates learning for typical individuals. This issue was explored in 7 experiments. In…

  2. When Does Fading Enhance Perceptual Category Learning?

    ERIC Educational Resources Information Center

    Pashler, Harold; Mozer, Michael C.

    2013-01-01

    Training that uses exaggerated versions of a stimulus discrimination (fading) has sometimes been found to enhance category learning, mostly in studies involving animals and impaired populations. However, little is known about whether and when fading facilitates learning for typical individuals. This issue was explored in 7 experiments. In…

  3. ENHANCEMENTS TO NATURAL ATTENUATION: SELECTED CASE STUDIES

    SciTech Connect

    Vangelas, K; W. H. Albright, W; E. S. Becvar, E; C. H. Benson, C; T. O. Early, T; E. Hood, E; P. M. Jardine, P; M. Lorah, M; E. Majche, E; D. Major, D; W. J. Waugh, W; G. Wein, G; O. R. West, O

    2007-05-15

    In 2003 the US Department of Energy (DOE) embarked on a project to explore an innovative approach to remediation of subsurface contaminant plumes that focused on introducing mechanisms for augmenting natural attenuation to achieve site closure. Termed enhanced attenuation (EA), this approach has drawn its inspiration from the concept of monitored natural attenuation (MNA).

  4. Prior Knowledge Enhances the Category Dimensionality Effect

    PubMed Central

    Hoffman, Aaron B.; Harris, Harlan D.; Murphy, Gregory L.

    2008-01-01

    A study of the combined influence of prior knowledge and stimulus dimensionality on category learning was conducted. Subjects learned category structures with the same number of necessary dimensions but more or fewer additional redundant dimensions, and with either knowledge-related or knowledge-unrelated features. Minimal-learning models predict that all subjects, regardless of condition, should learn either the same number of dimensions, or else should respond more slowly to each dimension. Despite similar learning rates and response times, subjects learned more features in the high-dimensional than in the low-dimensional condition. Furthermore, prior knowledge interacted with dimensionality, increasing what was learned especially in the high-dimensional case. A second experiment confirmed that the participants did in fact learn more features during the training phase, rather than simply inferring them at test. These effects can be explained by direct associations among features (representing prior knowledge) combined with feedback between features and the category label, as shown by simulations of the knowledge-resonance, or KRES, model of category learning. PMID:18426059

  5. N1 response attenuation and the mismatch negativity (MMN) to within- and across-category phonetic contrasts.

    PubMed

    Silva, Daniel M R; Melges, Danilo B; Rothe-Neves, Rui

    2017-04-01

    According to the neural adaptation model of the mismatch negativity (MMN), the sensitivity of this event-related response to both acoustic and categorical information in speech sounds can be accounted for by assuming that (a) the degree of overlapping between neural representations of two sounds depends on both the acoustic difference between them and whether or not they belong to distinct phonetic categories, and (b) a release from stimulus-specific adaptation causes an enhanced N1 obligatory response to infrequent deviant stimuli. On the basis of this view, we tested in Experiment 1 whether the N1 response to the second sound of a pair (S2 ) would be more attenuated in pairs of identical vowels compared with pairs of different vowels, and in pairs of exemplars of the same vowel category compared with pairs of exemplars of different categories. The psychoacoustic distance between S1 and S2 was the same for all within-category and across-category pairs. While N1 amplitudes decreased markedly from S1 to S2 , responses to S2 were quite similar across pair types, indicating that the attenuation effect in such conditions is not stimulus specific. In Experiment 2, a pronounced MMN was elicited by a deviant vowel sound in an across-category oddball sequence, but not when the exact same deviant vowel was presented in a within-category oddball sequence. This adds evidence that MMN reflects categorical phonetic processing. Taken together, the results suggest that different neural processes underlie the attenuation of the N1 response to S2 and the MMN to vowels. © 2017 Society for Psychophysiological Research.

  6. Enhanced Attenuation Technologies: Passive Soil Vapor Extraction

    SciTech Connect

    Vangelas, K.; Looney, B.; Kamath, R.; Adamson, D.; Newell, C.

    2010-03-15

    Passive soil vapor extraction (PSVE) is an enhanced attenuation (EA) approach that removes volatile contaminants from soil. The extraction is driven by natural pressure gradients between the subsurface and atmosphere (Barometric Pumping), or by renewable sources of energy such as wind or solar power (Assisted PSVE). The technology is applicable for remediating sites with low levels of contamination and for transitioning sites from active source technologies such as active soil vapor extraction (ASVE) to natural attenuation. PSVE systems are simple to design and operate and are more cost effective than active systems in many scenarios. Thus, PSVE is often appropriate as an interim-remedial or polishing strategy. Over the past decade, PSVE has been demonstrated in the U.S. and in Europe. These demonstrations provide practical information to assist in selecting, designing and implementing the technology. These demonstrations indicate that the technology can be effective in achieving remedial objectives in a timely fashion. The keys to success include: (1) Application at sites where the residual source quantities, and associated fluxes to groundwater, are relatively low; (2) Selection of the appropriate passive energy source - barometric pumping in cases with a deep vadose zone and barrier (e.g., clay) layers that separate the subsurface from the atmosphere and renewable energy assisted PSVE in other settings and where higher flow rates are required. (3) Provision of sufficient access to the contaminated vadose zones through the spacing and number of extraction wells. This PSVE technology report provides a summary of the relevant technical background, real-world case study performance, key design and cost considerations, and a scenario-based cost evaluation. The key design and cost considerations are organized into a flowchart that dovetails with the Enhanced Attenuation: Chlorinated Organics Guidance of the Interstate Technology and Regulatory Council (ITRC). The PSVE

  7. GROUND WATER REMEDIATION RESEARCH: ENHANCED BIOREMEDIATION AND MONITORED NATURAL ATTENUATION

    EPA Science Inventory

    An overview of ground water remediation research conducted at the Subsurface Protection and Remediation Division is provided. The focus of the overview is on Enhanced Bioremediation and Monitored Natural Attenuation research for the remediation of organic and inorganic contamina...

  8. GROUND WATER REMEDIATION RESEARCH: ENHANCED BIOREMEDIATION AND MONITORED NATURAL ATTENUATION

    EPA Science Inventory

    An overview of ground water remediation research conducted at the Subsurface Protection and Remediation Division is provided. The focus of the overview is on Enhanced Bioremediation and Monitored Natural Attenuation research for the remediation of organic and inorganic contamina...

  9. Tick Passage Results in Enhanced Attenuation of Babesia bovis

    PubMed Central

    McElwain, Terry F.; Ueti, Massaro W.; Scoles, Glen A.; Reif, Kathryn E.; Lau, Audrey O. T.

    2014-01-01

    Serial blood passage of virulent Babesia bovis in splenectomized cattle results in attenuated derivatives that do not cause neurologic disease. Tick transmissibility can be lost with attenuation, but when retained, attenuated B. bovis can revert to virulence following tick passage. This study provides data showing that tick passage of the partially attenuated B. bovis T2Bo derivative strain further decreased virulence compared with intravenous inoculation of the same strain in infected animals. Ticks that acquired virulent or attenuated parasites by feeding on infected cattle were transmission fed on naive, splenectomized animals. While there was no significant difference between groups in the number of parasites in the midgut, hemolymph, or eggs of replete female ticks after acquisition feeding, animals infected with the attenuated parasites after tick transmission showed no clinical signs of babesiosis, unlike those receiving intravenous challenge with the same attenuated strain prior to tick passage. Additionally, there were significantly fewer parasites in blood and tissues of animals infected with tick-passaged attenuated parasites. Sequencing analysis of select B. bovis genes before and after tick passage showed significant differences in parasite genotypes in both peripheral blood and cerebral samples. These results provide evidence that not only is tick transmissibility retained by the attenuated T2Bo strain, but also it results in enhanced attenuation and is accompanied by expansion of parasite subpopulations during tick passage that may be associated with the change in disease phenotype. PMID:25114111

  10. Tick passage results in enhanced attenuation of Babesia bovis.

    PubMed

    Sondgeroth, Kerry S; McElwain, Terry F; Ueti, Massaro W; Scoles, Glen A; Reif, Kathryn E; Lau, Audrey O T

    2014-10-01

    Serial blood passage of virulent Babesia bovis in splenectomized cattle results in attenuated derivatives that do not cause neurologic disease. Tick transmissibility can be lost with attenuation, but when retained, attenuated B. bovis can revert to virulence following tick passage. This study provides data showing that tick passage of the partially attenuated B. bovis T2Bo derivative strain further decreased virulence compared with intravenous inoculation of the same strain in infected animals. Ticks that acquired virulent or attenuated parasites by feeding on infected cattle were transmission fed on naive, splenectomized animals. While there was no significant difference between groups in the number of parasites in the midgut, hemolymph, or eggs of replete female ticks after acquisition feeding, animals infected with the attenuated parasites after tick transmission showed no clinical signs of babesiosis, unlike those receiving intravenous challenge with the same attenuated strain prior to tick passage. Additionally, there were significantly fewer parasites in blood and tissues of animals infected with tick-passaged attenuated parasites. Sequencing analysis of select B. bovis genes before and after tick passage showed significant differences in parasite genotypes in both peripheral blood and cerebral samples. These results provide evidence that not only is tick transmissibility retained by the attenuated T2Bo strain, but also it results in enhanced attenuation and is accompanied by expansion of parasite subpopulations during tick passage that may be associated with the change in disease phenotype. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  11. Working Memory Load Attenuates Emotional Enhancement in Recognition Memory

    PubMed Central

    Miendlarzewska, Ewa A.; van Elswijk, Gijs; Cannistraci, Carlo V.; van Ee, Raymond

    2013-01-01

    Emotionally arousing stimuli are perceived and remembered better than neutral stimuli. Under threat, this negativity bias is further increased. We investigated whether working memory (WM) load can attenuate incidental memory for emotional images. Two groups of participants performed the N-back task with two WM load levels. In one group, we induced anxiety using a threat of shock paradigm to increase attentional processing of negative information. During task performance we incidentally and briefly flashed emotional distracter images which prolonged response times in both load conditions. A subsequent unannounced immediate recognition memory test revealed that when load at exposure had been low, recognition was better for negative items in both participant groups. This enhancement, however, was attenuated under high load, leaving performance on neutral items unchanged regardless of the threat of shock manipulation. We conclude that both in threat and in normal states WM load at exposure can attenuate immediate emotional memory enhancement. PMID:23515565

  12. Monitored natural attenuation and enhanced attenuation for chlorinated solvent plumes - It's all about balance

    USGS Publications Warehouse

    Adams, K.A.; Vangelas, K.M.; Looney, B.B.; Chapelle, F.; Early, T.; Gilmore, T.; Sink, C.H.

    2005-01-01

    Nature's inherent ability to cleanse itself is at the heart of Monitored Natural Attenuation (MNA). The complexity comes when one attempts to measure and calculate this inherent ability, called the Natural Attenuation Capacity (NAC), and determine if it is sufficient to cleanse the system to agreed upon criteria. An approach that is simple in concept for determining whether the NAC is sufficient for MNA to work is the concept of a mass balance. Mass balance is a robust framework upon which all decisions can be made. The inflows to and outflows from the system are balanced against the NAC of the subsurface system. For MNA to be acceptable, the NAC is balanced against the contaminant loading to the subsurface system with the resulting outflow from the system being in a range that is acceptable to the regulating and decision-making parties. When the system is such that the resulting outflow is not within an acceptable range, the idea of taking actions that are sustainable and that will bring the system within the acceptable range of outflows is evaluated. These sustainable enhancements are being developed under the Enhanced Attenuation (EA) concept. Copyright ASCE 2005.

  13. Music enhances category fluency in healthy older adults and Alzheimer's disease patients.

    PubMed

    Thompson, R G; Moulin, C J A; Hayre, S; Jones, R W

    2005-01-01

    Exposure to some music, in particular classical music, has been reported to produce transient increases in cognitive performance. The authors investigated the effect of listening to an excerpt of Vivaldi's Four Seasons on category fluency in healthy older adult controls and Alzheimer's disease patients. In a counterbalanced repeated-measure design, participants completed two, 1-min category fluency tasks whilst listening to an excerpt of Vivaldi and two, 1-min category fluency tasks without music. The authors report a positive effect of music on category fluency, with performance in the music condition exceeding performance without music in both the healthy older adult control participants and the Alzheimer's disease patients. In keeping with previous reports, the authors conclude that music enhances attentional processes, and that this can be demonstrated in Alzheimer's disease.

  14. Reproducibility and discriminability of brain patterns of semantic categories enhanced by congruent audiovisual stimuli.

    PubMed

    Li, Yuanqing; Wang, Guangyi; Long, Jinyi; Yu, Zhuliang; Huang, Biao; Li, Xiaojian; Yu, Tianyou; Liang, Changhong; Li, Zheng; Sun, Pei

    2011-01-01

    One of the central questions in cognitive neuroscience is the precise neural representation, or brain pattern, associated with a semantic category. In this study, we explored the influence of audiovisual stimuli on the brain patterns of concepts or semantic categories through a functional magnetic resonance imaging (fMRI) experiment. We used a pattern search method to extract brain patterns corresponding to two semantic categories: "old people" and "young people." These brain patterns were elicited by semantically congruent audiovisual, semantically incongruent audiovisual, unimodal visual, and unimodal auditory stimuli belonging to the two semantic categories. We calculated the reproducibility index, which measures the similarity of the patterns within the same category. We also decoded the semantic categories from these brain patterns. The decoding accuracy reflects the discriminability of the brain patterns between two categories. The results showed that both the reproducibility index of brain patterns and the decoding accuracy were significantly higher for semantically congruent audiovisual stimuli than for unimodal visual and unimodal auditory stimuli, while the semantically incongruent stimuli did not elicit brain patterns with significantly higher reproducibility index or decoding accuracy. Thus, the semantically congruent audiovisual stimuli enhanced the within-class reproducibility of brain patterns and the between-class discriminability of brain patterns, and facilitate neural representations of semantic categories or concepts. Furthermore, we analyzed the brain activity in superior temporal sulcus and middle temporal gyrus (STS/MTG). The strength of the fMRI signal and the reproducibility index were enhanced by the semantically congruent audiovisual stimuli. Our results support the use of the reproducibility index as a potential tool to supplement the fMRI signal amplitude for evaluating multimodal integration.

  15. Therapeutic enhancement: nursing intervention category for patients diagnosed with Readiness for Therapeutic Regimen Management.

    PubMed

    Kelly, Cynthia W

    2008-04-01

    To present a new nursing intervention category called therapeutic enhancement. Fewer than half of North Americans follow their physician's recommendations for diet and exercise, even when such are crucial to their health or recovery. It is imperative that nurses consider new ways to promote healthy behaviours. Therapeutic enhancement is intended to provide such a fresh approach. Traditional intervention techniques focusing on education, contracts, social support and more frequent interaction with physicians appear not to be effective when used alone. Successful strategies have been multidisciplinary; and have included interventions by professional nurses who assist patients to understand their disease and the disease process and that helps them to develop disease-management and self-management skills. Therapeutic enhancement incorporates The Stages of Change Theory, Commitment to Health Theory, Motivational Interviewing techniques and instrumentation specifically designed for process evaluation of health-promoting interventions. This is a critical review of approaches that, heretofore, have not been synthesised in a single published article. Based on the commonly used Stages of Change model, therapeutic enhancement is useful for patients who are at the action stage of change. Using therapeutic enhancement as well as therapeutic strategies identified in Stages of Change Theory, such as contingency management, helping relationships, counterconditioning, stimulus control and Motivational Interviewing techniques, nursing professionals can significantly increase the chances of patients moving from action to the maintenance stage of change for a specific health behaviour. Using the nursing intervention category, therapeutic enhancement can increase caregivers' success in helping patients maintain healthy behaviours.

  16. Is discrimination enhanced at the boundaries of perceptual categories? A negative case

    PubMed Central

    Danilova, M. V.; Mollon, J. D.

    2014-01-01

    The human visual system imposes discrete perceptual categories on the continuous input space that is represented by the ratios of excitations of the cones in the retina. Is discrimination enhanced at the boundaries between perceptual hues, in the way that discrimination may be enhanced at the boundaries between speech sounds in hearing? In the chromaticity diagram, the locus of unique green separates colours that appear yellowish from those that appear bluish. Using a two-alternative spatial forced choice and an adapting field equivalent to the Daylight Illuminant D65, we measured chromatic discrimination along lines orthogonal to the locus of unique green. In experimental runs interleaved with these performance measurements, we obtained estimates of the phenomenological boundary from the same observers. No enhancement of objectively measured discrimination was observed at the category boundary between yellowish and bluish hues. Instead, thresholds were minimal at chromaticities where the ratio of long-wave to middle-wave cone excitation was the same as that for the background adapting field. PMID:24807255

  17. Is discrimination enhanced at the boundaries of perceptual categories? A negative case.

    PubMed

    Danilova, M V; Mollon, J D

    2014-06-22

    The human visual system imposes discrete perceptual categories on the continuous input space that is represented by the ratios of excitations of the cones in the retina. Is discrimination enhanced at the boundaries between perceptual hues, in the way that discrimination may be enhanced at the boundaries between speech sounds in hearing? In the chromaticity diagram, the locus of unique green separates colours that appear yellowish from those that appear bluish. Using a two-alternative spatial forced choice and an adapting field equivalent to the Daylight Illuminant D65, we measured chromatic discrimination along lines orthogonal to the locus of unique green. In experimental runs interleaved with these performance measurements, we obtained estimates of the phenomenological boundary from the same observers. No enhancement of objectively measured discrimination was observed at the category boundary between yellowish and bluish hues. Instead, thresholds were minimal at chromaticities where the ratio of long-wave to middle-wave cone excitation was the same as that for the background adapting field.

  18. Vowel category boundaries enhance cortical and behavioral responses to speech feedback alterations.

    PubMed

    Niziolek, Caroline A; Guenther, Frank H

    2013-07-17

    Auditory feedback is instrumental in the online control of speech, allowing speakers to compare their self-produced speech signal with a desired auditory target and correct for errors. However, there is little account of the representation of "target" and "error": does error depend purely on acoustic distance from a target, or is error enhanced by phoneme category changes? Here, we show an effect of vowel boundaries on compensatory responses to a real-time auditory perturbation. While human subjects spoke monosyllabic words, event-triggered functional magnetic resonance imaging was used to characterize neural responses to unexpected changes in auditory feedback. Capitalizing on speakers' natural variability, we contrasted the responses to feedback perturbations applied to two classes of utterances: (1) those that fell nearer to the category boundary, for which perturbations were designed to change the phonemic identity of the heard speech; and (2) those that fell farther from the boundary, for which perturbations resulted in only sub-phonemic auditory differences. Subjects' behavioral compensation was more than three times greater when feedback shifts were applied nearer to a category boundary. Furthermore, a near-boundary shift resulted in stronger cortical responses, most notably in right posterior superior temporal gyrus, than an identical shift that occurred far from the boundary. Across participants, a correlation was found between the amount of compensation to the perturbation and the amount of activity in a network of superior temporal and inferior frontal brain regions. Together, these results demonstrate that auditory feedback control of speech is sensitive to linguistic categories learned through auditory experience.

  19. Monitored Natural Attenuation and Enhanced Attenuation for Chlorinated Solvent Plumes - It’s All About Balance

    SciTech Connect

    VANGELAS, KAREN

    2005-05-19

    Nature's inherent ability to cleanse itself is at the heart of Monitored Natural Attenuation (MNA). The complexity comes when one attempts to measure and calculate this inherent ability, called the Natural Attenuation Capacity (NAC), and determine if it is sufficient to cleanse the system to agreed upon criteria. An approach that is simple in concept for determining whether the NAC is sufficient for MNA to work is the concept of a mass balance. Mass balance is a robust framework upon which all decisions can be made. The inflows to and outflows from the system are balanced against the NAC of the subsurface system. For MNA to be acceptable, the NAC is balanced against the contaminant loading to the subsurface system with the resulting outflow from the system being in a range that is acceptable to the regulating and decision-making parties. When the system is such that the resulting outflow is not within an acceptable range, the idea of taking actions that are sustainable and that will bring the system within the acceptable range of outflows is evaluated. These sustainable enhancements are being developed under the Enhanced Attenuation (EA) concept.

  20. Characterization of Small Focal Renal Lesions: Diagnostic Accuracy with Single-Phase Contrast-enhanced Dual-Energy CT with Material Attenuation Analysis Compared with Conventional Attenuation Measurements.

    PubMed

    Marin, Daniele; Davis, Drew; Roy Choudhury, Kingshuk; Patel, Bhavik; Gupta, Rajan T; Mileto, Achille; Nelson, Rendon C

    2017-03-28

    Purpose To determine whether single-phase contrast material-enhanced dual-energy material attenuation analysis improves the characterization of small (1-4 cm) renal lesions compared with conventional attenuation measurements by using histopathologic analysis and follow-up imaging as the clinical reference standards. Materials and Methods In this retrospective, HIPAA-compliant, institutional review board-approved study, 136 consecutive patients (95 men and 41 women; mean age, 54 years) with 144 renal lesions (111 benign, 33 malignant) measuring 1-4 cm underwent single-energy unenhanced and contrast-enhanced dual-energy computed tomography (CT) of the abdomen. For each renal lesion, attenuation measurements were obtained; attenuation change of greater than or equal to 15 HU was considered evidence of enhancement. Dual-energy attenuation measurements were also obtained by using iodine-water, water-iodine, calcium-water, and water-calcium material basis pairs. Mean lesion attenuation values and material densities were compared between benign and malignant renal lesions by using the two-sample t test. Diagnostic accuracy of attenuation measurements and dual-energy material densities was assessed and validated by using 10-fold cross-validation to limit the effect of optimistic bias. Results By using cross-validated optimal thresholds at 100% sensitivity, iodine-water material attenuation images significantly improved specificity for differentiating between benign and malignant renal lesions compared with conventional enhancement measurements (93% [103 of 111]; 95% confidence interval: 86%, 97%; vs 81% [90 of 111]; 95% confidence interval: 73%, 88%) (P = .02). Sensitivity with iodine-water and calcium-water material attenuation images was also higher than that with conventional enhancement measurements, although the difference was not statistically significant. Conclusion Contrast-enhanced dual-energy CT with material attenuation analysis improves specificity for

  1. Attenuation Correction and Normalisation for Quantification of Contrast Enhancement in Ultrasound Images of Carotid Arteries.

    PubMed

    Cheung, Wing Keung; Gujral, Dorothy M; Shah, Benoy N; Chahal, Navtej S; Bhattacharyya, Sanjeev; Cosgrove, David O; Eckersley, Robert J; Harrington, Kevin J; Senior, Roxy; Nutting, Christopher M; Tang, Meng-Xing

    2015-07-01

    An automated attenuation correction and normalisation algorithm was developed to improve the quantification of contrast enhancement in ultrasound images of carotid arteries. The algorithm first corrects attenuation artefact and normalises intensity within the contrast agent-filled lumen and then extends the correction and normalisation to regions beyond the lumen. The algorithm was first validated on phantoms consisting of contrast agent-filled vessels embedded in tissue-mimicking materials of known attenuation. It was subsequently applied to in vivo contrast-enhanced ultrasound (CEUS) images of human carotid arteries. Both in vitro and in vivo results indicated significant reduction in the shadowing artefact and improved homogeneity within the carotid lumens after the correction. The error in quantification of microbubble contrast enhancement caused by attenuation on phantoms was reduced from 55% to 5% on average. In conclusion, the proposed method exhibited great potential in reducing attenuation artefact and improving quantification in contrast-enhanced ultrasound of carotid arteries. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  2. Elevated Depressive Symptoms Enhance Reflexive but not Reflective Auditory Category Learning

    PubMed Central

    Maddox, W. Todd; Chandrasekaran, Bharath; Smayda, Kirsten; Yi, Han-Gyol; Koslov, Seth; Beevers, Christopher G.

    2014-01-01

    In vision an extensive literature supports the existence of competitive dual-processing systems of category learning that are grounded in neuroscience and are partially-dissociable. The reflective system is prefrontally-mediated and uses working memory and executive attention to develop and test rules for classifying in an explicit fashion. The reflexive system is striatally-mediated and operates by implicitly associating perception with actions that lead to reinforcement. Although categorization is fundamental to auditory processing, little is known about the learning systems that mediate auditory categorization and even less is known about the effects of individual difference in the relative efficiency of the two learning systems. Previous studies have shown that individuals with elevated depressive symptoms show deficits in reflective processing. We exploit this finding to test critical predictions of the dual-learning systems model in audition. Specifically, we examine the extent to which the two systems are dissociable and competitive. We predicted that elevated depressive symptoms would lead to reflective-optimal learning deficits but reflexive-optimal learning advantages. Because natural speech category learning is reflexive in nature, we made the prediction that elevated depressive symptoms would lead to superior speech learning. In support of our predictions, individuals with elevated depressive symptoms showed a deficit in reflective-optimal auditory category learning, but an advantage in reflexive-optimal auditory category learning. In addition, individuals with elevated depressive symptoms showed an advantage in learning a non-native speech category structure. Computational modeling suggested that the elevated depressive symptom advantage was due to faster, more accurate, and more frequent use of reflexive category learning strategies in individuals with elevated depressive symptoms. The implications of this work for dual-process approach to auditory

  3. ADVANCING THE SCIENCE OF NATURAL AND ENHANCED ATTENUATION FOR CHLORINATED SOLVENTS

    SciTech Connect

    Looney, B; TOM O. EARLY, T; TYLER GILMORE, T; FRANCIS H. CHAPELLE, F; NORMAN H. CUTSHALL, N; JEFF ROSS, J; MARK ANKENY, M; Michael Heitkamp, M; DAVID MAJOR, D; CHARLES J. NEWELL, C; W. JODY WAUGH, W; GARY WEIN, G; Karen Vangelas, K; Karen-M Adams, K; CLAIRE H. SINK, C

    2006-12-27

    This report summarizes the results of a three-year program that addressed key scientific and technical aspects related to natural and enhanced attenuation of chlorinated organics. The results from this coordinated three-year program support a variety of technical and regulatory advancements. Scientists, regulators, engineers, end-users and stakeholders participated in the program, which was supported by the U.S. Department of Energy (DOE) and the Interstate Technology and Regulatory Council (ITRC). The overarching objective of the effort was to examine environmental remedies that are based on natural processes--remedies such as Monitored Natural Attenuation (MNA) or Enhanced Attenuation (EA). A key result of the recent effort was the general affirmation of the approaches and guidance in the original U.S. Environmental Protection Agency (EPA) chlorinated solvent MNA protocols and directives from 1998 and 1999, respectively. The research program did identify several specific opportunities for advances based on: (1) mass balance as the central framework for attenuation based remedies, (2) scientific advancements and achievements during the past ten years, (3) regulatory and policy development and real-world experience using MNA, and (4) exploration of various ideas for integrating attenuation remedies into a systematic set of ''combined remedies'' for contaminated sites. These opportunities are summarized herein and are addressed in more detail in referenced project documents and journal articles, as well as in the technical and regulatory documents being developed within the ITRC. Natural attenuation processes occur in all soil and groundwater systems and act, to varying degrees, on all contaminants. Thus, a decision to rely on natural attenuation processes as part of a site-remediation strategy does not depend on the occurrence of natural attenuation, but on its effectiveness in meeting site-specific remediation goals. Meeting these goals typically requires low risk

  4. POTENTIAL ENHANCEMENTS TO NATURAL ATTENUATION: LINES OF INQUIRY SUPPORTING ENHANCED PASSIVE REMEDIATION OF CHLORINATED SOLVENTS

    SciTech Connect

    Vangelas, K; Tom Early, T; Michael Heitkamp, M; Brian02 Looney, B; David Major, D; Brian Riha, B; Jody Waugh, J; Gary Wein, G

    2004-06-18

    The Department of Energy (DOE) is sponsoring an initiative to facilitate efficient, effective and responsible use of Monitored Natural Attenuation (MNA) and Enhanced Passive Remediation (EPR) for chlorinated solvents. This Office of Environmental Management (EM) ''Alternative Project,'' focuses on providing scientific and policy support for MNA/EPR. A broadly representative working group of scientists supports the project along with partnerships with regulatory organizations such as the Interstate Technology and Regulatory Council and the U.S. Environmental Protection Agency (EPA). The initial product of the technical working group was a summary report that articulated the conceptual approach and central scientific tenants of the project, and that identified a prioritized listing of technical targets for field research. This report documented the process in which: (1) scientific ground rules were developed, (2) lines of inquiry were identified and then critically evaluated, (3) promising applied research topics were highlighted in the various lines of inquiry, and (4) these were discussed and prioritized. The summary report will serve as a resource to guide management and decision-making throughout the period of the subject MNA/EPR Alternative Project. To support and more fully document the information presented in the summary report, we are publishing a series of supplemental documents that present the full texts from the technical analyses within the various lines of inquiry (see listing). The following report - documenting our evaluation of the state of the science of the characterization and monitoring process and tools-- is one of those supplemental documents.

  5. MASS BALANCE: A KEY TO ADVANCING MONITORED AND ENHANCED ATTENUATION FOR CHLORINATED SOLVENTS

    SciTech Connect

    Looney, B; Karen Vangelas, K; Karen-M Adams, K; Francis H. Chappelle; Tom O. Early; Claire H. Sink

    2006-06-30

    Monitored natural attenuation (MNA) and enhanced attenuation (EA) are two environmental management strategies that rely on a variety of attenuation processes to degrade or immobilize contaminants and are implemented at appropriate sites by demonstrating that contaminant plumes have low risk and are stable or shrinking. The concept of a mass balance between the loading and attenuation of contaminants in a groundwater system is a powerful framework for conceptualizing and documenting the relative stability of a contaminant plume. As a result, this concept has significant potential to support appropriate implementation of monitored natural attenuation (MNA) and enhanced attenuation (EA). For mass balance to be useful in engineering practice, however, it is necessary to quantify it in practical ways that facilitate overall site remediation and which are consistent with existing regulatory guidance. Two divergent philosophies exist for quantifying plume stability--empirical and deterministic. The first relies on historical contaminant concentration data and bulk geochemical information from a monitoring well network and documents plume stability using trend analysis and statistical tools. This empirical approach, when feasible, provides powerful and compelling documentation of plume behavior and mass balance. It provides an interpretation on a relevant scale under field conditions. It integrates the operative attenuation processes measured by observing their actual impact on the plume. The power of the empirical approach was recognized early in the development of MNA guidance and protocols and it is currently the basis of the three lines of evidence used in MNA studies. The empirical approach has some weaknesses, however. It requires a relatively long period of undisturbed historical data. Thus it cannot be effectively applied to sites where active remediation was initiated quickly and is currently operating. It cannot be used as a tool to determine how much source

  6. Multiple Lines Of Evidence Supporting Natural Attenuation: Lines Of Inquiry Supporting Monitored Natural Attenuation And Enhanced Attenuatin Of Chlorinated Solvents

    SciTech Connect

    Vangelas, Karen; Widemeirer, T. H.; Barden, M.J.; Dickson, W. Z.; Major, David

    2004-12-31

    The Department of Energy (DOE) is sponsoring an initiative to facilitate efficient, effective and responsible use of Monitored Natural Attenuation (MNA) and Enhanced Attenuation (EA) for chlorinated solvents. This Office of Environmental Management (EM) ''Alternative Project,'' focuses on providing scientific and policy support for MNA/EA. A broadly representative working group of scientists supports the project along with partnerships with regulatory organizations such as the Interstate Technology Regulatory Council (ITRC) and the United States Environmental Protection Agency (USEPA). The initial product of the technical working group was a summary report that articulated the conceptual approach and central scientific tenants of the project, and that identified a prioritized listing of technical targets for field research. This report documented the process in which: (1) scientific ground rules were developed, (2) lines of inquiry were identified and then critically evaluated, (3) promising applied research topics were highlighted in the various lines of inquiry, and (4) these were discussed and prioritized. The summary report will serve as a resource to guide management and decision making throughout the period of the subject MNA/EA Alternative Project. To support and more fully document the information presented in the summary report, the DOE is publishing a series of supplemental documents that present the full texts from the technical analyses within the various lines of inquiry (see listing). The following report--documenting our evaluation of the state of the science for the lines of evidence for supporting decision-making for MNA--is one of those supplemental documents.

  7. Vibration attenuations induced by periodic arrays of piezoelectric patches connected by enhanced resonant shunting circuits

    NASA Astrophysics Data System (ADS)

    Wang, Gang; Wang, Jianwei; Chen, Shengbing; Wen, Jihong

    2011-12-01

    Periodic arrays of piezoelectric patches connected by enhanced resonant shunting circuits are attached to a slender beam to control the propagation of vibration. Numerical models based on the transfer matrix methodology are constructed to predict the band structure, attenuation factors and the transmission of vibration in the proposed smart structure. The vibration attenuations of the proposed smart structure and that with the passive resonant shunting circuits are compared in order to verify the efficiency of the enhanced resonant shunting circuits. Vibration experiments are conducted in order to validate the theoretical predictions. The specimen with a combination of different types of resonant shunting circuits is also studied in order to gain wider attenuation frequency ranges.

  8. REDD1 attenuates cardiac hypertrophy via enhancing autophagy.

    PubMed

    Liu, Chen; Xue, Ruicong; Wu, Dexi; Wu, Lingling; Chen, Cong; Tan, Weiping; Chen, Yili; Dong, Yugang

    2014-11-07

    Cardiac hypertrophy is a major risk factor of cardiovascular morbidity and mortality. Autophagy is established to be involved in regulating cardiac hypertrophy. REDD1, a stress-responsive protein, is proved to contribute in autophagy induction. However, the role of REDD1 in cardiac hypertrophy remains unknown. Our study demonstrated that REDD1 knockdown by RNAi exacerbated phenylephrine (PE)-induced cardiac hypertrophy, manifested by increased hypertrophic markers such as ANP and cell surface area. In addition, we discovered that ERK1/2 signaling pathway was involved in the effect of REDD1 on hypertrophy. Moreover, our study showed that REDD1 knockdown impaired autophagy in hypertrophied cardiomyocytes. mTOR, a signaling molecule governing autophagy induction, was activated by the knockdown of REDD1 under PE stress. Importantly, the pro-hypertrophic effect of REDD1 knockdown was significantly reversed by the autophagy enhancer rapamycin. Taken together, we firstly prove that REDD1 is essential for inhibiting cardiac hypertrophy by enhancing autophagy. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Enhanced procedural learning of speech sound categories in a genetic variant of FOXP2.

    PubMed

    Chandrasekaran, Bharath; Yi, Han-Gyol; Blanco, Nathaniel J; McGeary, John E; Maddox, W Todd

    2015-05-20

    A mutation of the forkhead box protein P2 (FOXP2) gene is associated with severe deficits in human speech and language acquisition. In rodents, the humanized form of FOXP2 promotes faster switching from declarative to procedural learning strategies when the two learning systems compete. Here, we examined a polymorphism of FOXP2 (rs6980093) in humans (214 adults; 111 females) for associations with non-native speech category learning success. Neurocomputational modeling results showed that individuals with the GG genotype shifted faster to procedural learning strategies, which are optimal for the task. These findings support an adaptive role for the FOXP2 gene in modulating the function of neural learning systems that have a direct bearing on human speech category learning.

  10. ENHANCED ATTENUATION: A REFERENCE GUIDE ON APPROACHES TO INCREASE THE NATURAL TREATMENT CAPACITY OF A SYSTEM

    SciTech Connect

    Looney, B; Michael Heitkamp, M; Gary Wein , G; Karen Vangelas, K; Karen-M Adams, K; Tom Early; Bob Borden; David Major; W. Jody Waugh; Todd Wiedemeier; Claire H. Sink

    2006-08-10

    The objective of this document is to explore the realm of enhancements to natural attenuation processes for cVOCs and review examples that have been proposed, modeled, and implemented. We will identify lessons learned from these case studies to confirm that enhancements are technically feasible and have the potential to achieve a favorable, cost-effective contaminant mass balance. Furthermore, we hope to determine if opportunities for further improvement of the enhancements exist and suggest areas where new and innovative types of enhancements might be possible.

  11. Enhanced Attenuation: A Reference Guide On Approaches To Increase The Natural Treatment Capacity Of A System

    SciTech Connect

    Vangelas, K

    2006-01-30

    The objective of this document is to explore the realm of enhancements to natural attenuation processes for cVOCs and review examples that have been proposed, modeled, and implemented. We will identify lessons learned from these case studies to confirm that enhancements are technically feasible and have the potential to achieve a favorable, cost-effective contaminant mass balance. Furthermore, we hope to determine if opportunities for further improvement of the enhancements exist and suggest areas where new and innovative types of enhancements might be possible.

  12. Contrast enhanced CT attenuation correlates with the GAG content of bovine meniscus.

    PubMed

    Lakin, Bejamin A; Grasso, Daniel J; Stewart, Rachel C; Freedman, Jonathan D; Snyder, Brian D; Grinstaff, Mark W

    2013-11-01

    We determined whether contrast-enhanced computed tomography (CECT) attenuation obtained using a µCT scanner correlated with the glycosaminoglycan (GAG) content and distribution in ex vivo bovine menisci. Bovine samples were immersed in different concentrations of the contrast agents CA4+ and Ioxaglate, and the µCT images were compared to Safranin-O staining. CA4+ and Ioxaglate diffusion-in kinetics and the correlation between their CECT attenuations and GAG content were investigated. CA4+ and Ioxaglate both reached steady state in the meniscal regions within 95 h, with tau values of 20.6 ± 3.98 and 25.9 ± 3.71 h (mean ± SD), respectively. Both agents diffused preferentially through the proximal and secondarily through the distal surface. The CA4+ CECT attenuation was strongly and positively correlated with the GAG content of the meniscus regions (R(2)  = 0.89, p < 0.001) at low concentrations (12 mgI/ml), while the Ioxaglate CECT attenuation was moderately and negatively correlated with the GAG content (R(2)  = 0.51, p = 0.03) at 60 mgI/ml. CECT can image ex vivo menisci, and the CA4+, compared to Ioxaglate, enhanced attenuation strongly correlates with the GAG content and distribution in bovine meniscus.

  13. Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

    SciTech Connect

    Lee, Yoon Jae; Jang, Yo Han; Kim, Paul; Lee, Yun Ha; Lee, Young Jae; Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik; Seong, Baik Lin

    2016-04-15

    In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

  14. Proapoptotic protein Bim attenuates estrogen-enhanced survival in lymphangioleiomyomatosis

    PubMed Central

    Li, Chenggang; Li, Na; Liu, Xiaolei; Zhang, Erik Y.; Sun, Yang; Masuda, Kouhei; Li, Jing; Sun, Julia; Morrison, Tasha; Li, Xiangke; Chen, Yuanguang; Wang, Jiang; Karim, Nagla A.; Zhang, Yi; Blenis, John; Reginato, Mauricio J.; Henske, Elizabeth P.; Yu, Jane J.

    2016-01-01

    Lymphangioleiomyomatosis (LAM) is a progressive lung disease that primarily affects young women. Genetic evidence suggests that LAM cells bearing TSC2 mutations migrate to the lungs, proliferate, and cause cystic remodeling. The female predominance indicates that estrogen plays a critical role in LAM pathogenesis, and we have proposed that estrogen promotes LAM cell metastasis by inhibition of anoikis. We report here that estrogen increased LAM patient–derived cells’ resistance to anoikis in vitro, accompanied by decreased accumulation of the proapoptotic protein Bim, an activator of anoikis. The resistance to anoikis was reversed by the proteasome inhibitor, bortezomib. Treatment of LAM patient–derived cells with estrogen plus bortezomib promoted anoikis compared with estrogen alone. Depletion of Bim by siRNA in TSC2-deficient cells resulted in anoikis resistance. Treatment of mice with bortezomib reduced estrogen-promoted lung colonization of TSC2-deficient cells. Importantly, molecular depletion of Bim by siRNA in Tsc2-deficient cells increased lung colonization in a mouse model. Collectively, these data indicate that Bim plays a key role in estrogen-enhanced survival of LAM patient–derived cells under detached conditions that occur with dissemination. Thus, targeting Bim may be a plausible future treatment strategy in patients with LAM. PMID:27882343

  15. Proapoptotic protein Bim attenuates estrogen-enhanced survival in lymphangioleiomyomatosis.

    PubMed

    Li, Chenggang; Li, Na; Liu, Xiaolei; Zhang, Erik Y; Sun, Yang; Masuda, Kouhei; Li, Jing; Sun, Julia; Morrison, Tasha; Li, Xiangke; Chen, Yuanguang; Wang, Jiang; Karim, Nagla A; Zhang, Yi; Blenis, John; Reginato, Mauricio J; Henske, Elizabeth P; Yu, Jane J

    2016-11-17

    Lymphangioleiomyomatosis (LAM) is a progressive lung disease that primarily affects young women. Genetic evidence suggests that LAM cells bearing TSC2 mutations migrate to the lungs, proliferate, and cause cystic remodeling. The female predominance indicates that estrogen plays a critical role in LAM pathogenesis, and we have proposed that estrogen promotes LAM cell metastasis by inhibition of anoikis. We report here that estrogen increased LAM patient-derived cells' resistance to anoikis in vitro, accompanied by decreased accumulation of the proapoptotic protein Bim, an activator of anoikis. The resistance to anoikis was reversed by the proteasome inhibitor, bortezomib. Treatment of LAM patient-derived cells with estrogen plus bortezomib promoted anoikis compared with estrogen alone. Depletion of Bim by siRNA in TSC2-deficient cells resulted in anoikis resistance. Treatment of mice with bortezomib reduced estrogen-promoted lung colonization of TSC2-deficient cells. Importantly, molecular depletion of Bim by siRNA in Tsc2-deficient cells increased lung colonization in a mouse model. Collectively, these data indicate that Bim plays a key role in estrogen-enhanced survival of LAM patient-derived cells under detached conditions that occur with dissemination. Thus, targeting Bim may be a plausible future treatment strategy in patients with LAM.

  16. Multiband enhanced absorption of monolayer graphene with attenuated total reflectance configuration and sensing application

    NASA Astrophysics Data System (ADS)

    Wang, Nan; Bu, Lingbing; Chen, Yunyun; Zheng, Gaige; Zou, Xiujuan; Xu, Linhua; Wang, Jicheng

    2017-01-01

    An enhanced absorption of monolayer graphene is obtained in a multilayer film-based attenuated total reflectance configuration in the visible wavelength range. The enhanced absorption under transverse magnetic and electric conditions is associated with the excitation of the waveguide mode in the thin-film layer, which is verified by the numerical calculation of field profiles. The obtained results manifest that the model induces a high field enhancement at the graphene-dielectric interface with the resonant angle, which implies potential sensing applications. The magnitude of the figure of merit is found to be three times higher than that of a conventional surface plasmon sensor.

  17. The use of error-category mapping in pharmacokinetic model analysis of dynamic contrast-enhanced MRI data.

    PubMed

    Gill, Andrew B; Anandappa, Gayathri; Patterson, Andrew J; Priest, Andrew N; Graves, Martin J; Janowitz, Tobias; Jodrell, Duncan I; Eisen, Tim; Lomas, David J

    2015-02-01

    This study introduces the use of 'error-category mapping' in the interpretation of pharmacokinetic (PK) model parameter results derived from dynamic contrast-enhanced (DCE-) MRI data. Eleven patients with metastatic renal cell carcinoma were enrolled in a multiparametric study of the treatment effects of bevacizumab. For the purposes of the present analysis, DCE-MRI data from two identical pre-treatment examinations were analysed by application of the extended Tofts model (eTM), using in turn a model arterial input function (AIF), an individually-measured AIF and a sample-average AIF. PK model parameter maps were calculated. Errors in the signal-to-gadolinium concentration ([Gd]) conversion process and the model-fitting process itself were assigned to category codes on a voxel-by-voxel basis, thereby forming a colour-coded 'error-category map' for each imaged slice. These maps were found to be repeatable between patient visits and showed that the eTM converged adequately in the majority of voxels in all the tumours studied. However, the maps also clearly indicated sub-regions of low Gd uptake and of non-convergence of the model in nearly all tumours. The non-physical condition ve ≥ 1 was the most frequently indicated error category and appeared sensitive to the form of AIF used. This simple method for visualisation of errors in DCE-MRI could be used as a routine quality-control technique and also has the potential to reveal otherwise hidden patterns of failure in PK model applications.

  18. Magnetoencephalography Reveals Mismatch Field Enhancement from Unexpected Syntactic Category Errors in English Sentences.

    PubMed

    Kubota, Mikio; Ono, Yumie; Ishiyama, Atsushi; Zouridakis, George; Papanicolaou, Andrew C

    2017-08-25

    The type of syntactic operations that increase neuronal activation in humans as a result of syntactically erroneous, unexpected lexical items in hearing sentences has remained unclear. In the present study, we used recordings of magnetoencephalographic (MEG) activity to compare bare infinitive and full infinitive constructions in English. This research aims to identify the type of syntactic deviance that may trigger an early syntax-related mismatch field (MMF) component when unexpected words appear in sentences. Six speakers of English as a first language were presented with auditory stimuli of sentences or words in a passive odd-ball paradigm while watching a silent movie. The experimental protocol included four sessions, specifically investigating the sentential (structural) versions of full (with the 'to' infinitival particle) and bare infinitival structures (without the particle) and the lexical (non-structure) versions of the verb either with or without the particle to determine whether the structure processing of sentences was a more crucial factor in the detection of the MMF than the simple processing of lexical items in verb-only conditions. The amplitude analysis of the resulting evoked fields showed that the presence of the syntactic category error of bare infinitival structures against syntactic predictions evoked a significantly larger MMF activation with a peak latency of approximately 200ms in the anterior superior temporal sulci in the left hemisphere, compared with the lexical items that did not have any syntactic status. These results clearly demonstrate that syntactically unexpected, illegal input in the bare infinitival structure is likely to be noticed more robustly in the brain while processing the structural information of the entire sentence than the corresponding verb-only items. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Is discrimination enhanced at a category boundary? The case of unique red.

    PubMed

    Danilova, M V; Mollon, J D

    2016-03-01

    Is chromatic discrimination enhanced at the boundary between different hues? In previous studies, we gave a positive answer for the case of the locus of unique blues and yellows, the boundary that divides color space into reddish and greenish hues. But we did not find enhancement at the locus of unique green, the boundary between yellowish and bluish hues. In the present study, we examined discrimination near the locus of unique red. In interleaved experimental runs, we obtained (1) discrimination thresholds using a four-alternative spatial forced choice and (2) phenomenological judgments of the locus of unique red. When measurements were made along lines parallel to the locus of unique blues and yellows in a MacLeod-Boynton diagram, the locus of minimal thresholds coincided approximately with the locus of unique red; however, this was not the case when measurements were made along lines orthogonal to the locus of unique blues and yellows. To account for these and earlier results, we suppose that the neural channel that determines the discrimination threshold will sometimes coincide with the channel that determines the perceptual hue equilibrium and sometimes will not. If a given point in chromaticity space is a unique hue, then it is expected to remain a unique hue independently of the direction in which measurements are made; however, discrimination thresholds almost certainly will depend on different underlying channels when measurements are made in different directions through the same point in chromaticity space.

  20. The sigma receptor agonist SA4503 both attenuates and enhances the effects of methamphetamine

    PubMed Central

    Rodvelt, Kelli R.; Oelrichs, Clark E.; Blount, Lucas R.; Fan, Kuo-Hsien; Lever, Susan Z.; Lever, John R.; Miller, Dennis K.

    2011-01-01

    Background Methamphetamine’s behavioral effects have been attributed to its interaction with monoamine transporters; however, methamphetamine also has affinity for sigma receptors. Method The present study investigated the effect of the sigma receptor agonist SA 4503 and the sigma receptor antagonists BD-1047 and BD-1063 on methamphetamine-evoked [3H] dopamine release from preloaded rat striatal slices. The effect of SA 4503 on methamphetamine-induced hyperactivity and on the discriminative stimulus properties of methamphetamine also was determined. Results SA 4503 attenuated methamphetamine-evoked [3H]dopamine release in a concentration-dependent manner. BD-1047 and BD-1063 did not affect release. SA 4503 dose-dependently potentiated and attenuated methamphetamine-induced hyperactivity. SA 4503 pretreatment augmented the stimulus properties of methamphetamine. Conclusions Our findings indicate that SA 4503 both enhances and inhibits methamphetamine’s effects and that sigma receptors are involved in the neurochemical, locomotor stimulatory and discriminative stimulus properties of methamphetamine. PMID:21277708

  1. Enhanced natural attenuation of BTEX in the nitrate-reducing environment by different electron acceptors.

    PubMed

    Zhao, Yongsheng; Qu, Dan; Hou, Zhimin; Zhou, Rui

    2015-01-01

    Enhancing natural attenuation of benzene, toluene, ethylbenzene, and xylene (BTEX) in groundwater is a potential remediation technology. This study focused on selecting appropriate electron acceptors to promote BTEX degradation in a nitrate-reducing environment. Nitrate-reducing soil was obtained from simulated BTEX-contaminated column. Enhancing experiments were conducted in the microcosm with nitrate-reducing material and simulated BTEX-polluted groundwater to investigate the promoting feasibility of adding dissolved oxygen (DO), nitrate, chelated Fe(III), and sulphate as electron acceptors. The concentrations of BTEX, electron acceptors, and their reducing products were measured. The order of promoting BTEX degradation with four electron acceptors was nitrate>sulphate>chelated Fe(III)>DO, and the first-order decay coefficients were 0.0432, 0.0333, 0.0240, and 0.0155, respectively. Nitrate, sulphate, and chelated Fe(III) enhanced attenuation. Nitrate was the most effective electron acceptor under nitrate-reducing conditions. Selecting proper electron acceptor is significant in promoting BTEX degradation according to the biogeochemical characteristics of local underground environment.

  2. Underwater image enhancement based on the dark channel prior and attenuation compensation

    NASA Astrophysics Data System (ADS)

    Guo, Qingwen; Xue, Lulu; Tang, Ruichun; Guo, Lingrui

    2017-10-01

    Aimed at the two problems of underwater imaging, fog effect and color cast, an Improved Segmentation Dark Channel Prior (ISDCP) defogging method is proposed to solve the fog effects caused by physical properties of water. Due to mass refraction of light in the process of underwater imaging, fog effects would lead to image blurring. And color cast is closely related to different degree of attenuation while light with different wavelengths is traveling in water. The proposed method here integrates the ISDCP and quantitative histogram stretching techniques into the image enhancement procedure. Firstly, the threshold value is set during the refinement process of the transmission maps to identify the original mismatching, and to conduct the differentiated defogging process further. Secondly, a method of judging the propagating distance of light is adopted to get the attenuation degree of energy during the propagation underwater. Finally, the image histogram is stretched quantitatively in Red-Green-Blue channel respectively according to the degree of attenuation in each color channel. The proposed method ISDCP can reduce the computational complexity and improve the efficiency in terms of defogging effect to meet the real-time requirements. Qualitative and quantitative comparison for several different underwater scenes reveals that the proposed method can significantly improve the visibility compared with previous methods.

  3. Lab-based investigation of enhanced BTEX attenuation driven by groundwater table fluctuation.

    PubMed

    Yang, Y S; Li, Panpan; Zhang, Xi; Li, Mingjie; Lu, Ying; Xu, Bin; Yu, Tong

    2017-02-01

    Groundwater fluctuation is often overlooked and lack of study in the field contaminant hydrogeology. Hydraulic force from fluctuating groundwater tables leads to dissolution and subsequent enhanced advective transport of petroleum (e.g. BTEX) in contaminated subsurface system. A laboratory investigation of effect of the groundwater table fluctuation (GTF) on BTEX transport, taking toluene as a typical compound, in a typical representative model of aquifers subjected to a daily water-table fluctuation was undertaken in this work. Results showed that toluene in effluent degraded significantly with cycles of GTF, and the attenuation rates differed in porous media types with higher value for fine-coarse sand media (13.7 mg L(-1) d(-1)) and lower for fine sand-clay media (2.8 mg L d(-1)). Hydraulic and hydrochemical evidences inferred that toluene attenuation was controlled mainly by flushing effect in the initial GTF cycle stages, followed by dissolution and mixing action in the later stages. Meanwhile, adsorption was found to take effects in toluene behavior throughout the whole GTF process, particularly obvious in fine sand-clay media with its toluene attenuation rate of only 2.8 mg L d(-1).

  4. Differentiating Renal Neoplasms From Simple Cysts on Contrast-Enhanced CT on the Basis of Attenuation and Homogeneity.

    PubMed

    Agochukwu, Nnenaya; Huber, Steffen; Spektor, Michael; Goehler, Alexander; Israel, Gary M

    2017-04-01

    The purpose of this study is to compare the attenuation and homogeneity of renal neoplasms with those of cysts on contrast-enhanced CT. A total of 129 renal neoplasms and 24 simple cysts were evaluated. Two readers determined whether each mass was qualitatively heterogeneous or homogeneous. Mean, minimum, and maximum attenuation values were measured. Statistical analysis was performed. A total of 116 heterogeneous renal cell carcinomas (RCCs) (99 clear cell, four papillary, four oncocytic, seven chromophobe, and two unclassified RCCs), 13 homogeneous RCCs (10 papillary, two oncocytic, and one chromophobe RCC), and 24 cysts (all of which were homogeneous) were evaluated. All homogeneous RCCs had mean attenuation values of more than 42 HU, whereas renal cysts had mean attenuation values of up to 30 HU (p < 0.001). Two readers qualitatively and identically categorized all RCCs as homogeneous or heterogeneous (κ = 1.0; p < 0.001). Homogeneous simple renal cysts can have mean attenuation values of up to 30 HU, as determined by contrast-enhanced CT, whereas homogeneous RCCs have mean attenuation values as low as 42 HU, with no overlap occurring between the two groups. These data suggest that further evaluation of a homogeneous renal mass with a mean attenuation value of 30 HU or less on a contrast-enhanced CT scan likely is unwarranted.

  5. Transcription bypass of DNA lesions enhances cell survival but attenuates transcription coupled DNA repair.

    PubMed

    Li, Wentao; Selvam, Kathiresan; Ko, Tengyu; Li, Shisheng

    2014-12-01

    Transcription-coupled DNA repair (TCR) is a subpathway of nucleotide excision repair (NER) dedicated to rapid removal of DNA lesions in the transcribed strand of actively transcribed genes. The precise nature of the TCR signal and how the repair machinery gains access to lesions imbedded in stalled RNA polymerase II (RNAP II) complexes in eukaryotic cells are still enigmatic. RNAP II has an intrinsic capacity for transcription bypass of DNA lesions by incorporation or misincorporation of nucleotides across the lesions. It has been suggested that transcription bypass of lesions, which exposes the lesions, may be required for TCR. Here, we show that E1103G mutation of Rpb1, the largest subunit of RNAP II, which promotes transcription bypass of UV-induced cyclobutane pyrimidine dimers (CPDs), increases survival of UV irradiated yeast cells but attenuates TCR. The increased cell survival is independent of any NER subpathways. In contrast, G730D mutation of Rpb1, which impairs transcription bypass of CPDs, enhances TCR. Our results suggest that transcription bypass of lesions attenuates TCR but enhances cell tolerance to DNA lesions. Efficient stalling of RNAP II is essential for efficient TCR. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. SU-E-T-151: Enhanced Radiation Attenuation with Multi-Layer Foils

    SciTech Connect

    Warmington, L; Watanabe, Y

    2014-06-01

    Purpose: To evaluate the effect of increasing the number of thin high Z foils on the dose enhancement and the overall radiation attenuation with a 24MV photon beam. Methods: DOSXYZnrc was used to perform Monte Carlo simulations of multi-layer lead foil configurations. The foil size was 7cm x 7cm. and the foil thickness was adjusted to give a combined thickness of 1mm. The number of foils used was 4, 6, 8, and 10. The separation between foils was also varied from 3 to 9 mm. The Mohan 24MV energy spectrum was used as a photon source. The field size was 5cm x 5cm and SSD was 100 cm. The phantom size was 16cm × 16cm × 28cm. The number of histories ranged from 1 to 2 billion. The percentage difference of the dose between the medium with foils and the homogeneous water was computed along the beam axis. The minimum dose enhancement and the change of integrated dose between the foils were determined. Results: Increasing the number of foils resulted in a decrease in the minimum dose enhancement. The highest dose region occurred in the last section for the 4 and 6 foil cases, whereas the 8 and 10 foil configurations showed the maximum dose region towards the center of the foil group. Increasing the number of foils increased the total integrated dose between foils. For example, the total integrated dose increase between the first and the last foils with a 3mm foil separation were 34.2, 43.4, 57.4, and 64.7% for 4, 6, 8 and 10 foils, respectively. Conclusion: This work showed the degree of dose enhancement around multiple thin lead foils. The results suggest that the total attenuation of photon beam can be increased by increasing the number of foils with a fixed total foil thickness.

  7. Development of a Mouse-Adapted Live Attenuated Influenza Virus That Permits In Vivo Analysis of Enhancements to the Safety of Live Attenuated Influenza Virus Vaccine

    PubMed Central

    Cox, Andrew; Baker, Steven F.; Nogales, Aitor

    2014-01-01

    The live attenuated influenza virus vaccine (LAIV) is preferentially recommended for use in persons 2 through 49 years of age but has not been approved for children under 2 or asthmatics due to safety concerns. Therefore, increasing safety is desirable. Here we describe a murine LAIV with reduced pathogenicity that retains lethality at high doses and further demonstrate that we can enhance safety in vivo through mutations within NS1. This model may permit preliminary safety analysis of improved LAIVs. PMID:25552727

  8. Sildenafil does not enhance but rather attenuates vasorelaxant effects of antidiabetic agents

    PubMed Central

    Peuler, Jacob D.; Phelps, Laura E.

    2015-01-01

    Type 2 diabetic men commonly experience erectile dysfunction for which phosphodiesterase-5 (PDE5) inhibitors like sildenafil (Viagra) are often recommended. By preventing degradation of cyclic guanosine monophosphate (cGMP) in vascular smooth muscle, these inhibitors also enhance arterial vasorelaxant effects of nitric oxide donors (which stimulate cGMP synthesis). In the present work, we confirmed this enhancing effect after co-administration of sildenafil with nitroprusside to freshly-isolated rat tail arterial tissues. However, in the same tissues we also observed that sildenafil does not enhance but rather attenuates vasorelaxant effects of three commonly-used antidiabetic drugs, i.e. the biguanide metformin and the thiazolidinediones pioglitazone and rosiglitazone. Indeed, sildenafil completely blocked vasorelaxant effects of low concentrations of these drugs. In addition, we found that this same novel anti-vasorelaxant interaction of sildenafil with these agents was abolished by either 1) omitting extracellular glucose or 2) inhibiting specific smooth muscle glycolytic pathways; pathways known to preferentially utilize extracellular glucose to fuel certain adenosine triphosphate (ATP)-dependent ion transporters: e.g. ATP-sensitive K channels, sarcoplasmic reticulum Ca-ATPase, plasma membrane Ca-ATPase and Na/K-ATPase. Accordingly, we suspect that altered activity of one or more of these ion transporters mediates the observed attenuating (anti-vasorelaxant) interaction of sildenafil with the antidiabetic drugs. The present results are relevant because hypertension is so common and difficult to control in Type 2 diabetes. The present data suggest that sildenafil might interfere with the known antihypertensive potential of metformin and the thiazolidinediones. However, they do not suggest that it will interact with them to cause life-threatening episodes of severe hypotension, as can occur when it is co-administered with nitrates. PMID:26004378

  9. L-ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1.

    PubMed

    Huang, Ya-Ni; Wang, Jiz-Yuh; Lee, Ching-Tien; Lin, Chih-Hung; Lai, Chien-Cheng; Wang, Jia-Yi

    2012-12-01

    Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of l-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2',7'-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. The metabolic enhancer piracetam attenuates mitochondrion-specific endonuclease G translocation and oxidative DNA fragmentation.

    PubMed

    Gupta, Sonam; Verma, Dinesh Kumar; Biswas, Joyshree; Rama Raju, K Siva; Joshi, Neeraj; Wahajuddin; Singh, Sarika

    2014-08-01

    This study was performed to investigate the involvement of mitochondrion-specific endonuclease G in piracetam (P)-induced protective mechanisms. Studies have shown the antiapoptotic effects of piracetam but the mechanism of action of piracetam is still an enigma. To assess the involvement of endonuclease G in piracetam-induced protective effects, astrocyte glial cells were treated with lipopolysaccharide (LPS) and piracetam. LPS treatment caused significantly decreased viability, mitochondrial activity, oxidative stress, chromatin condensation, and DNA fragmentation, which were attenuated by piracetam cotreatment. Cotreatment of astrocytes with piracetam showed its significantly time-dependent absorption as observed with high-performance liquid chromatography. Astrocytes treated with piracetam alone showed enhanced mitochondrial membrane potential (MMP) in comparison to control astrocytes. However, in LPS-treated cells no significant alteration in MMP was observed in comparison to control cells. Protein and mRNA levels of the terminal executor of the caspase-mediated pathway, caspase-3, were not altered significantly in LPS or LPS + piracetam-treated astrocytes, whereas endonuclease G was significantly translocated to the nucleus in LPS-treated astrocytes. Piracetam cotreatment attenuated the LPS-induced endonuclease G translocation. In conclusion this study indicates that LPS treatment of astrocytes caused decreased viability, oxidative stress, mitochondrial dysfunction, chromatin condensation, DNA damage, and translocation of endonuclease G to the nucleus, which was inhibited by piracetam cotreatment, confirming that the mitochondrion-specific endonuclease G is one of the factors involved in piracetam-induced protective mechanisms. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Pulsed gas injection: a minimum effort approach for enhanced natural attenuation of chlorobenzene in contaminated groundwater.

    PubMed

    Balcke, Gerd Ulrich; Paschke, Heidrun; Vogt, Carsten; Schirmer, Mario

    2009-07-01

    Chlorobenzene-contaminated groundwater was used to assess pulsed gas sparging as a minimum effort aeration strategy to enhance intrinsic natural attenuation. In contrast to existing biosparging operations, oxygen was supplied at minimum rate by reducing the gas injection frequency to 0.33 day(-1). Field tests in a model aquifer were conducted in a 12 m long reactor, filled with indigenous aquifer material and continuously recharged with polluted groundwater over 3 years. The closed arrangement allowed yield balances, cost accounting as well as the investigation of spatial distributions of parameters which are sensitive to the biodegradation process. Depending on the injection frequency and on the gas chosen for injection (pure oxygen or air) oxygen-deficient conditions prevailed in the aquifer. Despite the limiting availability of dissolved oxygen in the groundwater, chlorobenzene degradation under oxygen-deficient conditions proved to be more effective than under conditions with dissolved oxygen being available in high concentrations.

  12. Categorial Grammars.

    ERIC Educational Resources Information Center

    Wood, Mary McGee; Hudson, Richard, Ed.

    Written as an objective critical assessment, this book is the first linguistic theory guide to categorial grammars. Categorial grammars offer a radical alternative to the phrase-structure paradigm, with roots in the philosophy of language, logic, and algebra. Their historical evolution is outlined and their formal basis is discussed, beginning…

  13. Defensins attenuate cytokine responses yet enhance antibody responses to Porphyromonas gingivalis adhesins in mice

    PubMed Central

    Kohlgraf, Karl G; Ackermann, Abbey; Lu, Xiaoying; Burnell, Kindra; Bélanger, Myriam; Cavanaugh, Joseph E; Xie, Hua; Progulske-Fox, Ann; Brogden, Kim A

    2010-01-01

    Aim Our aim is to assess the ability of human neutrophil peptide α-defensins (HNPs) and human β-defensins (HBDs) to attenuate proinflammatory cytokine responses and enhance antibody responses to recombinant hemagglutinin B (rHagB) or recombinant fimbrillin A (rFimA) from Porphyromonas gingivalis 381 in mice. Materials & methods In the first study, C57BL/6 mice were given 10 μg rHagB or rFimA without and with 1 μg HNP1, HNP2, HBD1, HBD2 or HBD3. At 24 h, mice were euthanized and cytokine concentrations were determined in nasal wash fluid (NWF), bronchoalveolar lavage fluids, saliva and serum. In the second study, C57BL/6 mice were given 10 μg rHagB or rFimA without and with 1 μg HNPs or HBDs similarly on days 0, 7 and 14. At 21 days, mice were euthanized and rHagB- and rFimA-specific antibody responses were determined in NWF, bronchoalveolar lavage fluids, saliva and serum. Results Mice given rHagB + HNP2, rHagB + HBD1 and rHagB + HBD3 produced significantly lower (p < 0.05) IL-6 responses than mice given rHagB alone. Mice given rHagB + HNP1, rHagB + HNP2, rHagB + HBD1 and rHagB + HBD3 produced significantly lower (p < 0.05) keratinocyte-derived chemokine responses than mice given rHagB alone. Mice given rFimA produced very low levels of IL-6 and only moderate levels of keratinocyte-derived chemokine in NWF that were not attenuated by prior incubation of rFimA with any defensin. Mice given rHagB + HNP1 produced a significantly higher (p < 0.05) serum IgG antibody response than mice given rHagB alone and mice given rFimA + HNP2 produced a higher, but not significant, antibody response. Conclusion The ability of HNPs and HBDs to attenuate proinflammatory cytokine responses in murine NWF and enhance IgG antibody responses in serum was dependent upon both the defensin and antigen of P. gingivalis. PMID:20020833

  14. The role of clay in enhancing attenuation of trace organic contaminants during managed aquifer recharge

    NASA Astrophysics Data System (ADS)

    Regnery, J.; Strasser, A.; Hake, E.; Wing, A.; Drewes, J. E.

    2013-12-01

    For more hydrophobic trace organic contaminants present in surface water or reclaimed water applied for managed aquifer recharge (MAR), sorption onto organic matter can play a major role in attenuation in subsurface systems as the retardation allows more time for biotransformation. In case of low organic matter, other sorptive processes such as interactions with mineral surfaces gain importance. Especially for positively charged molecules, sorption onto clay materials by cation exchange will play a significant role. However, if the cation exchange capacity is limited or sorption of trace organic contaminants to clay materials is reversible due to changes in geochemical conditions (i.e., pH, ion strength), this might not provide a sustainable removal pathway. The objective of this study is to investigate how sorption to clay can enhance the removal of trace organic contaminants during MAR with the goal of evaluating the feasibility (i.e., infiltration capacity) and benefit (i.e., retardation of recalcitrant compounds) of introducing clay materials as reactive barriers in MAR systems. Laboratory-scale soil column experiments and batch sorption experiments using well characterized soil mixtures with different clay percentages under abiotic conditions and spiked at environmentally relevant concentration levels were conducted to derive soil water distribution coefficients for a suite of 15 trace organic chemicals (i.e., pharmaceutical residues, personal care products, household chemicals) and to quantify their sorption/desorption potential. All clay materials used in this study were characterized by X-ray diffraction to obtain information regarding their sorption processes. Furthermore, results were compared with geochemical field data from a full-scale MAR site in Colorado where significant amounts of clay in the subsurface were present. Preliminary results indicated that certain clay materials bear a great potential to retain moderately hydrophobic compounds such as

  15. TH-C-204-02: Improving Manuscript Quality Via Structured Reviews, Enhanced Scientific Category Taxonomy, and Outreach.

    PubMed

    Das, S

    2016-06-01

    timely topics and solicit high profile authors to submit review manuscripts. To submit an article, authors will need to work with an assigned Co-Editor to develop a mutually acceptable outline and abstract. 5) A new and exciting class of articles: Medical Physics Dataset Articles (MPDAs) MPDAs describe scientifically or clinically valuable open-access datasets with high potential for contributing to the research of medical physicists working on related problems. In contrast to Research Articles, MPDAs should not include hypothesis testing; or data analyses supporting generalizable conclusions. The publically accessible dataset must be permanently archived before the MPDA can be published. This initiative is being led by Joe Deasy. Update on new publisher transition: The transition of AAPM scientific publishing operations to a major publishing house is a major opportunity to expand Medical Physics readership and its scholarly impact. The advantages include: (a) common manuscript management and web hosting platforms for Medical Physics and its sister journal, JACMP; (b) greater than 4-fold expansion of subscribing institutions; and (c) resources to mount data-driven, highly targeted marketing campaigns to enhance citation and download rates. A transition update of this epochal development, which has only begun as of this writing (3/31/16), will be given. Improving manuscript quality via structured reviews, enhanced scientific category taxonomy, and outreach: Shiva Das, Therapy Physics Editor Medical Physics is committed to continuous improvement with the ultimate goal of improving the potential impact of accepted manuscripts. In order to do so, Medical Physics must be able to tap into important/emerging areas and be able to select high quality contributions consistently via discerning reviews. Improving the quality of reviews is crucial to selecting high quality manuscripts and also to improving manuscript impact via feedback in the review process. With this in mind

  16. Ginsenoside Rg3 enhances islet cell function and attenuates apoptosis in mouse islets.

    PubMed

    Kim, S S; Jang, H J; Oh, M Y; Eom, D W; Kang, K S; Kim, Y J; Lee, J H; Ham, J Y; Choi, S Y; Wee, Y M; Kim, Y H; Han, D J

    2014-05-01

    The transplantation of isolated islets is thought to be an attractive approach for curative treatment of diabetes mellitus. Panax ginseng has been used in oriental countries for its pharmacologic effects, such as antidiabetic and antiinflammatory activities. 20(S)-ginsenoside Rg3 (Rg3), an active ingredient of ginseng saponins, has been reported to enhance insulin secretion-stimulating and antiapoptotic activities in pancreatic beta cells. We performed this study to examine the hypothesis that preoperative Rg3 administration can enhance islet cell function and antiapoptosis before islet transplantation. Balb/c mice were randomly divided into 2 groups according to the administration of Rg3 after islet isolation. Mouse islets were cultured in medium supplemented with or without Rg3. In vitro, islet viability and function were assessed. After treatment of islets with a cytokine cocktail (tumor necrosis factor α, interferon-γ, and interleukin-1β), cell viability, function, and apoptosis were assessed. Cell viability was similar between the 2 groups. Islets cultured in medium supplemented with Rg3 showed 2.3-fold higher glucose-induced insulin secretion than islets cultured in medium without Rg3. After treatment with a cytokine cocktail, glucose-induced insulin release, total insulin content of islets, and apoptosis were significantly improved in Rg3-treated islets compared with cytokine-treated islets. Cytokine-treated islets produced significantly higher levels of nitric oxide (NO) than islets treated with Rg3. These results suggest that preoperative Rg3 administration enhanced islet function before islet transplantation and attenuated both cytokine-induced damage associated with NO production and apoptosis. Rg3 administration might be a prospective management to enhanced islet function and ameliorate early inflammation after transplantation. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Enhancing astrocytic lysosome biogenesis facilitates Aβ clearance and attenuates amyloid plaque pathogenesis.

    PubMed

    Xiao, Qingli; Yan, Ping; Ma, Xiucui; Liu, Haiyan; Perez, Ronaldo; Zhu, Alec; Gonzales, Ernesto; Burchett, Jack M; Schuler, Dorothy R; Cirrito, John R; Diwan, Abhinav; Lee, Jin-Moo

    2014-07-16

    In sporadic Alzheimer's disease (AD), impaired Aβ removal contributes to elevated extracellular Aβ levels that drive amyloid plaque pathogenesis. Extracellular proteolysis, export across the blood-brain barrier, and cellular uptake facilitate physiologic Aβ clearance. Astrocytes can take up and degrade Aβ, but it remains unclear whether this function is insufficient in AD or can be enhanced to accelerate Aβ removal. Additionally, age-related dysfunction of lysosomes, the major degradative organelles wherein Aβ localizes after uptake, has been implicated in amyloid plaque pathogenesis. We tested the hypothesis that enhancing lysosomal function in astrocytes with transcription factor EB (TFEB), a master regulator of lysosome biogenesis, would promote Aβ uptake and catabolism and attenuate plaque pathogenesis. Exogenous TFEB localized to the nucleus with transcriptional induction of lysosomal biogenesis and function in vitro. This resulted in significantly accelerated uptake of exogenously applied Aβ42, with increased localization to and degradation within lysosomes in C17.2 cells and primary astrocytes, indicating that TFEB is sufficient to coordinately enhance uptake, trafficking, and degradation of Aβ. Stereotactic injection of adeno-associated viral particles carrying TFEB driven by a glial fibrillary acidic protein promoter was used to achieve astrocyte-specific expression in the hippocampus of APP/PS1 transgenic mice. Exogenous TFEB localized to astrocyte nuclei and enhanced lysosome function, resulting in reduced Aβ levels and shortened half-life in the brain interstitial fluid and reduced amyloid plaque load in the hippocampus compared with control virus-injected mice. Therefore, activation of TFEB in astrocytes is an effective strategy to restore adequate Aβ removal and counter amyloid plaque pathogenesis in AD. Copyright © 2014 the authors 0270-6474/14/349607-14$15.00/0.

  18. Enhancing Astrocytic Lysosome Biogenesis Facilitates Aβ Clearance and Attenuates Amyloid Plaque Pathogenesis

    PubMed Central

    Xiao, Qingli; Yan, Ping; Ma, Xiucui; Liu, Haiyan; Perez, Ronaldo; Zhu, Alec; Gonzales, Ernesto; Burchett, Jack M.; Schuler, Dorothy R.; Cirrito, John R.

    2014-01-01

    In sporadic Alzheimer's disease (AD), impaired Aβ removal contributes to elevated extracellular Aβ levels that drive amyloid plaque pathogenesis. Extracellular proteolysis, export across the blood–brain barrier, and cellular uptake facilitate physiologic Aβ clearance. Astrocytes can take up and degrade Aβ, but it remains unclear whether this function is insufficient in AD or can be enhanced to accelerate Aβ removal. Additionally, age-related dysfunction of lysosomes, the major degradative organelles wherein Aβ localizes after uptake, has been implicated in amyloid plaque pathogenesis. We tested the hypothesis that enhancing lysosomal function in astrocytes with transcription factor EB (TFEB), a master regulator of lysosome biogenesis, would promote Aβ uptake and catabolism and attenuate plaque pathogenesis. Exogenous TFEB localized to the nucleus with transcriptional induction of lysosomal biogenesis and function in vitro. This resulted in significantly accelerated uptake of exogenously applied Aβ42, with increased localization to and degradation within lysosomes in C17.2 cells and primary astrocytes, indicating that TFEB is sufficient to coordinately enhance uptake, trafficking, and degradation of Aβ. Stereotactic injection of adeno-associated viral particles carrying TFEB driven by a glial fibrillary acidic protein promoter was used to achieve astrocyte-specific expression in the hippocampus of APP/PS1 transgenic mice. Exogenous TFEB localized to astrocyte nuclei and enhanced lysosome function, resulting in reduced Aβ levels and shortened half-life in the brain interstitial fluid and reduced amyloid plaque load in the hippocampus compared with control virus-injected mice. Therefore, activation of TFEB in astrocytes is an effective strategy to restore adequate Aβ removal and counter amyloid plaque pathogenesis in AD. PMID:25031402

  19. Reinforcement enhancing effect of nicotine and its attenuation by nicotinic antagonists in rats

    PubMed Central

    Liu, Xiu; Palmatier, Matthew I.; Caggiula, Anthony R.; Donny, Eric C.; Sved, Alan F.

    2010-01-01

    Rationale Recent studies have demonstrated that nicotine can enhance operant responding for other nonpharmacological reinforcing stimuli. However, the nature of the reinforcement-enhancing effect of nicotine remains largely unknown. Objective The present study determined the dose dependency of the ability of nicotine to increase lever-pressing responses maintained by a compound visual stimulus (VS) in rats and examined its sensitivity to pharmacological antagonism of nicotinic acetylcholine receptors (nAChRs). Materials and methods Male Sprague–Dawley rats were trained in daily 1-h sessions to lever press for delivery of a VS (1 s lever light on and 60 s house light off) on a fixed ratio 5 schedule. During these sessions, eight scheduled response-independent intravenous infusions of nicotine (total amount: 0, 0.06, 0.12, 0.24, 0.48 mg kg−1 h−1) were delivered. In pharmacological tests, a nonselective nAChR antagonist mecamylamine, α4β2-selective antagonist dihydro-β-erythroidine (DHβE), and α7-selective antagonist methyllycaconitine (MLA) were administered in different groups of rats 30 min before the session. Results The VS maintained a moderate level of lever-pressing responses and nicotine dose-dependently increased responses for the VS presentations. Preteatment of mecamylamine and DHβE but not MLA significantly attenuated the nicotine-enhanced responding. However, mecamylamine had no effect on responding for the VS in rats that received scheduled saline infusions. Conclusions These results demonstrate dose dependency of the reinforcement-enhancing effect of nicotine and suggest that activation of the α4β2- but not α7-containing nAChRs may mediate this effect. PMID:17616849

  20. Development of a mouse-adapted live attenuated influenza virus that permits in vivo analysis of enhancements to the safety of live attenuated influenza virus vaccine.

    PubMed

    Cox, Andrew; Baker, Steven F; Nogales, Aitor; Martínez-Sobrido, Luis; Dewhurst, Stephen

    2015-03-01

    The live attenuated influenza virus vaccine (LAIV) is preferentially recommended for use in persons 2 through 49 years of age but has not been approved for children under 2 or asthmatics due to safety concerns. Therefore, increasing safety is desirable. Here we describe a murine LAIV with reduced pathogenicity that retains lethality at high doses and further demonstrate that we can enhance safety in vivo through mutations within NS1. This model may permit preliminary safety analysis of improved LAIVs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. L-Ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1

    SciTech Connect

    Huang, Ya-Ni; Wang, Jiz-Yuh; Lee, Ching-Tien; Lin, Chih-Hung; Lai, Chien-Cheng; Wang, Jia-Yi

    2012-12-01

    Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of L-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2′,7′-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. -- Highlights: ► Besides the anti-oxidant effect, Vit. C also induces HO-1 expression in brain cells. ► Vit. C reduces METH neurotoxicity and ROS production by

  2. Organic Carbon Amendments for Enhanced Biological Attenuation of Trace Organic Contaminants in Biochar-Amended Stormwater Biofilters.

    PubMed

    Ulrich, Bridget A; Vignola, Marta; Edgehouse, Katelynn; Werner, David; Higgins, Christopher P

    2017-08-15

    This study sought to evaluate how dissolved organic carbon (DOC) affects attenuation of trace organic contaminants (TOrCs) in biochar-amended stormwater biofilters. It was hypothesized that (1) DOC-augmented runoff would demonstrate enhanced TOrC biodegradation and (2) biochar-amended sand bearing DOC-cultivated biofilms would achieve enhanced TOrC attenuation due to sorptive retention and biodegradation. Microcosm and column experiments were conducted utilizing actual runoff, DOC from straw and compost, and a suite of TOrCs. Biodegradation of TOrCs in runoff was more enhanced by compost DOC than straw DOC (particularly for atrazine, prometon, benzotriazole, and fipronil). 16S rRNA gene quantification and sequencing revealed that growth-induced microbial community changes were, among replicates, most consistent for compost-augmented microcosms and least consistent for raw runoff microcosms. Compost DOC most robustly enhanced utilization of TOrCs as carbon substrates, possibly due to higher residual nutrient levels upon TOrC exposure. Sand columns containing just 0.5 wt % biochar maintained sorptive TOrC retention in the presence of compost-DOC-cultivated biofilms, and TOrC removal was further enhanced by biological activity. Overall, these results suggest that coamendment with biochar and compost may robustly enhance TOrC attenuation in stormwater biofilters, a finding of significance for efforts to mitigate the impacts of runoff on water quality.

  3. Iron and carbon monoxide attenuate Crotalus atrox venom-enhanced tissue-type plasminogen activator-initiated fibrinolysis.

    PubMed

    Nielsen, Vance G; Boyer, Leslie V; Matika, Ryan W; Amos, Quinlan; Redford, Daniel T

    2016-07-01

    In addition to degrading fibrinogen as a source of consumptive coagulopathy, rattlesnake venom has also been demonstrated to enhance fibrinolysis and degrade alpha-2-antiplasmin. The goals of this investigation was to characterize the kinetic fibrinolytic profile of Crotalus atrox venom in the absence and presence of tissue-type plasminogen activator (tPA), and to also ascertain if iron and carbon monoxide (CO, a positive modulator of alpha-2-antiplasmin) could attenuate venom-enhanced fibrinolysis. Utilizing thrombelastographic methods, the coagulation and fibrinolytic kinetic profiles of human plasma exposed to C. atrox venom (0-2 μg/ml) were determined in the absence or presence of tPA (0-100 IU/ml). Then, either separately or in combination, plasma was exposed to iron (ferric chloride, 10 μmol/l) or CO (carbon monoxide-releasing molecule-2, 100 μmol/l) prior to incubation with venom; the plasma sample was subsequently subjected to thrombelastographic analysis with addition of tPA. Venom exposure in the absence of tPA did not result in detectable fibrinolysis. In the presence of tPA, venom markedly enhanced fibrinolysis. Iron and CO, markedly attenuated venom enhancement of fibrinolysis. C. atrox venom enhances tPA-mediated fibrinolysis, and interventions that enhance/protect alpha-2-antiplasmin activity significantly attenuate venom-enhanced fibrinolysis. Future preclinical investigation is required to determine if iron and CO can attenuate venom-mediated degradation of alpha-2-antiplasmin-dependent fibrinolytic resistance.

  4. Enhanced ultrasonic attenuation of Tl-Ca-Ba-Cu-O at the superconducting transition

    NASA Technical Reports Server (NTRS)

    Sun, K. J.; Winfree, W. P.; Xu, M.-F.; Levy, M.; Sarma, Bimal K.

    1990-01-01

    Temperature-dependent ultrasonic attenuation measurements have been performed on polycrystalline samples of Tl-Ca-Ba-Cu-O at various frequencies. An attenuation anomaly was observed close to the superconducting transition temperature T(c) (103 K) whose temperature position was frequency-independent. The attenuation decreased exponentially with temperature in the superconducting state for both transverse and longitudinal waves. It was also found that the temperature-dependent sound velocity showed a slope change around T(c).

  5. Bioavailability of residual polycyclic aromatic hydrocarbons following enhanced natural attenuation of creosote-contaminated soil.

    PubMed

    Juhasz, Albert L; Smith, Euan; Waller, Natasha; Stewart, Richard; Weber, John

    2010-02-01

    The impact of residual PAHs (2250 +/- 71 microg total PAHs g(-1)) following enhanced natural attenuation (ENA) of creosote-contaminated soil (7767 +/- 1286 microg total PAHs g(-1)) was assessed using a variety of ecological assays. Microtox results for aqueous soil extracts indicated that there was no significant difference in EC(50) values for uncontaminated, pre- and post-remediated soil. However, in studies conducted with Eisenia fetida, PAH bioaccumulation was reduced by up to 6.5-fold as a result of ENA. Similarly, Beta vulgaris L. biomass yields were increased 2.1-fold following ENA of creosote-contaminated soil. While earthworm and plant assays indicated that PAH bioavailability was reduced following ENA, the residual PAH fraction still exerted toxicological impacts on both receptors. Results from this study highlight that residual PAHs following ENA (presumably non-bioavailable to bioremediation) may still be bioavailable to important receptor organisms such as earthworms and plants. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  6. IL-33 targeting attenuates intestinal mucositis and enhances effective tumor chemotherapy in mice.

    PubMed

    Guabiraba, R; Besnard, A G; Menezes, G B; Secher, T; Jabir, M S; Amaral, S S; Braun, H; Lima-Junior, R C P; Ribeiro, R A; Cunha, F Q; Teixeira, M M; Beyaert, R; Graham, G J; Liew, F Y

    2014-09-01

    Intestinal damage and severe diarrhea are serious side effects of cancer chemotherapy and constrain the usage of most such therapies. Here we show that interleukin-33 (IL-33) mediates the severe intestinal mucositis in mice treated with irinotecan (CPT-11), a commonly used cancer chemotherapeutic agent. Systemic CPT-11 administration led to severe mucosal damage, diarrhea, and body weight loss concomitant with the induction of IL-33 in the small intestine (SI). This mucositis was markedly reduced in mice deficient in the IL-33R (ST2(-/-)). Moreover, recombinant IL-33 exacerbated the CPT-11-induced mucositis, whereas IL-33 blockade with anti-IL-33 antibody or soluble ST2 markedly attenuated the disease. CPT-11 treatment increased neutrophil accumulation in the SI and adhesion to mesenteric veins. Supernatants from SI explants treated with CPT-11 enhanced transmigration of neutrophils in vitro in an IL-33-, CXCL1/2-, and CXCR2-dependent manner. Importantly, IL-33 blockade reduced mucositis and enabled prolonged CPT-11 treatment of ectopic CT26 colon carcinoma, leading to a beneficial outcome of the chemotherapy. These results suggest that inhibition of the IL-33/ST2 pathway may represent a novel approach to limit mucositis and thus improve the effectiveness of chemotherapy.

  7. Quercetin Attenuates Chronic Ethanol-Induced Hepatic Mitochondrial Damage through Enhanced Mitophagy.

    PubMed

    Yu, Xiao; Xu, Yanyan; Zhang, Shanshan; Sun, Jian; Liu, Peiyi; Xiao, Lin; Tang, Yuhan; Liu, Liegang; Yao, Ping

    2016-01-05

    Emerging evidence suggested mitophagy activation mitigates ethanol-induced liver injury. However, the effect of ethanol on mitophagy is inconsistent. Importantly, the understanding of mitophagy status after chronic ethanol consumption is limited. This study evaluated the effect of quercetin, a naturally-occurring flavonoid, on chronic ethanol-induced mitochondrial damage focused on mitophagy. An ethanol regime to mice for 15 weeks (accounting for 30% of total calories) led to significant mitochondrial damage as evidenced by changes of the mitochondrial ultrastructure, loss of mitochondrial membrane potential and remodeling of membrane lipid composition, which was greatly attenuated by quercetin (100 mg/kg.bw). Moreover, quercetin blocked chronic ethanol-induced mitophagy suppression as denoted by mitophagosomes-lysosome fusion and mitophagy-related regulator elements, including LC3II, Parkin, p62 and voltage-dependent anion channel 1 (VDAC1), paralleling with increased FoxO3a nuclear translocation. AMP-activated protein kinase (AMPK) and extracellular signal regulated kinase 2 (ERK2), instead of AKT and Sirtuin 1, were involved in quercetin-mediated mitophagy activation. Quercetin alleviated ethanol-elicited mitochondrial damage through enhancing mitophagy, highlighting a promising preventive strategy for alcoholic liver disease.

  8. Quercetin Attenuates Chronic Ethanol-Induced Hepatic Mitochondrial Damage through Enhanced Mitophagy

    PubMed Central

    Yu, Xiao; Xu, Yanyan; Zhang, Shanshan; Sun, Jian; Liu, Peiyi; Xiao, Lin; Tang, Yuhan; Liu, Liegang; Yao, Ping

    2016-01-01

    Emerging evidence suggested mitophagy activation mitigates ethanol-induced liver injury. However, the effect of ethanol on mitophagy is inconsistent. Importantly, the understanding of mitophagy status after chronic ethanol consumption is limited. This study evaluated the effect of quercetin, a naturally-occurring flavonoid, on chronic ethanol-induced mitochondrial damage focused on mitophagy. An ethanol regime to mice for 15 weeks (accounting for 30% of total calories) led to significant mitochondrial damage as evidenced by changes of the mitochondrial ultrastructure, loss of mitochondrial membrane potential and remodeling of membrane lipid composition, which was greatly attenuated by quercetin (100 mg/kg.bw). Moreover, quercetin blocked chronic ethanol-induced mitophagy suppression as denoted by mitophagosomes-lysosome fusion and mitophagy-related regulator elements, including LC3II, Parkin, p62 and voltage-dependent anion channel 1 (VDAC1), paralleling with increased FoxO3a nuclear translocation. AMP-activated protein kinase (AMPK) and extracellular signal regulated kinase 2 (ERK2), instead of AKT and Sirtuin 1, were involved in quercetin-mediated mitophagy activation. Quercetin alleviated ethanol-elicited mitochondrial damage through enhancing mitophagy, highlighting a promising preventive strategy for alcoholic liver disease. PMID:26742072

  9. Attenuated Tonic and Enhanced Phasic Release of Dopamine in Attention Deficit Hyperactivity Disorder.

    PubMed

    Badgaiyan, Rajendra D; Sinha, Sampada; Sajjad, Munawwar; Wack, David S

    2015-01-01

    It is unclear whether attention deficit hyperactive disorder (ADHD) is a hypodopaminergic or hyperdopaminergic condition. Different sets of data suggest either hyperactive or hypoactive dopamine system. Since indirect methods used in earlier studies have arrived at contradictory conclusions, we directly measured the tonic and phasic release of dopamine in ADHD volunteers. The tonic release in ADHD and healthy control volunteers was measured and compared using dynamic molecular imaging technique. The phasic release during performance of Eriksen's flanker task was measured in the two groups using single scan dynamic molecular imaging technique. In these experiments volunteers were positioned in a positron emission tomography (PET) camera and administered a dopamine receptor ligand (11)C-raclopride intravenously. After the injection PET data were acquired dynamically while volunteers either stayed still (tonic release experiments) or performed the flanker task (phasic release experiments). PET data were analyzed to measure dynamic changes in ligand binding potential (BP) and other receptor kinetic parameters. The analysis revealed that at rest the ligand BP was significantly higher in the right caudate of ADHD volunteers suggesting reduced tonic release. During task performance significantly lower ligand BP was observed in the same area, indicating increased phasic release. In ADHD tonic release of dopamine is attenuated and the phasic release is enhanced in the right caudate. By characterizing the nature of dysregulated dopamine neurotransmission in ADHD, the results explain earlier findings of reduced or increased dopaminergic activity.

  10. Implementation of Enhanced Attenuation at the DOE Mound Site OU-1 Landfill: Accelerating Progress and Reducing Costs

    SciTech Connect

    Hooten, Gwendolyn; Cato, Rebecca; Looney, Brian

    2016-03-06

    At the US Department of Energy (DOE), Office of Legacy Management, Mound, Ohio, Site, chlorinated organic contaminants (cVOCs) originating from the former solid-waste landfill have impacted groundwater in Operable Unit 1 (OU-1). The baseline groundwater remedy was groundwater pump and treat (P&T). Since the source materials have been removed from the landfill, the Mound core team, which consists of DOE, US Environmental Protection Agency (US EPA), Ohio EPA, and other stakeholders, is assessing the feasibility of switching from the active P&T remedy to a passive attenuation-based remedy. Toward this end, an enhanced attenuation (EA) strategy based on the creation of structured geochemical zones was developed. This EA strategy addresses the residual areas of elevated cVOCs in soil and groundwater while minimizing the rebound of groundwater concentrations above regulatory targets (e.g., maximum contaminant levels [MCLs]) and avoiding plume expansion while the P&T system is turned off. The EA strategy has improved confidence and reduced risk on the OU-1 groundwater transition path to monitored natural attenuation (MNA). To better evaluate the EA strategy, DOE is conducting a field demonstration to evaluate the use of edible oils to enhance the natural attenuation processes. The field demonstration is designed to determine whether structured geochemical zones can be established that expedite the attenuation of cVOCs in the OU-1 groundwater. The EA approach at OU-1 was designed based on “structured geochemical zones” and relies on groundwater flow through a succession of anaerobic and aerobic zones. The anaerobic zones stimulate relatively rapid degradation of the original solvent source compounds (e.g., cVOCs such as tetrachloroethene [PCE] and trichloroethene [TCE]). The surrounding aerobic areas encourage relatively rapid degradation of daughter products (such as dichloroethene [DCE] and vinyl chloride [VC]) as well as enhanced cometabolism of TCE resulting from

  11. Attenuated Total Reflection Surface-Enhanced Infrared Absorption (ATR SEIRA) Spectroscopy for the Analysis of Fatty Acids on Silver Nanoparticles.

    PubMed

    Kato, Yuichi; Kikugawa, Masashi; Sudo, Eiichi

    2017-09-01

    The application of attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR SEIRA) to the analysis of fatty acids on silver nanoparticles was investigated. Attenuated total reflection measurements using four types of internal reflection elements (IREs)-zinc selenide, diamond, silicon, and germanium-were performed for silver nanoparticles modified with fatty acids, and germanium IRE was shown to be suitable for the analysis of silver nanoparticles, even when the sample had a high refractive index. Fatty acids coating the silver nanoparticles could be directly identified by SEIRA enhancement, because both symmetric carboxylate stretching vibration and methylene wagging vibration were strongly detected. Furthermore, the peak positions for methylene wagging vibration differed depending on the carbon number of the fatty acid, so that information from the ATR SEIRA spectra makes it possible to identify substances coating silver nanoparticles. Therefore, ATR SEIRA would appear to have significant potential as a technique for the identification of substances coated on metal nanoparticle surfaces.

  12. MOVING BEYOND PUMP AND TREAT TOWARD ENHANCED ATTENUATION AND COMBINED REMEDIES T-AREA, SAVANNAH RIVER SITE

    SciTech Connect

    Looney, B; Brian Riha, B; Warren Hyde, W; Jay Noonkester, J; Gerald Blount, G

    2008-04-03

    Groundwater beneath T-Area, a former laboratory and semiworks operation at the Department of Energy (DOE) Savannah River Site, is contaminated by chlorinated solvents (cVOCs). Since the contamination was detected in the 1980s, the cVOCs at T-Area have been treated by a combination of soil vapor extraction and groundwater pump and treat. The site has received approval to discontinue the active treatments and implement a full scale test of enhanced attenuation--an engineering and regulatory strategy that has recently been developed by DOE and the Interstate Technology and Regulatory Council. Enhanced attenuation uses active engineering solutions to alter the target site in such a way that the contaminant plume will passively stabilize and shrink and to document that the action will be effective, timely, and sustainable. The paradigm recognizes that attenuation remedies are fundamentally based on a mass balance. Thus, long-term plume dynamics can be altered either by reducing the contaminant loading from the source or by increasing the rate of natural attenuation processes within all, or part of, the plume volume. The combination of technologies that emerged for T-Area included: (1) neat (pure) vegetable oil deployment in the deep vadose zone in the former source area, (2) emulsified vegetable oil deployment within the footprint of the groundwater plume, and (3) identification of attenuation mechanisms and rates for the distal portion of the plume. In the first part, neat oil spreads laterally forming a thin layer on the water table to intercept and reduce future cVOC loading (via partitioning) and reduce oxygen inputs (via biostimulation). In the second and third parts, emulsified oil forms active bioremediation reactor zones within the plume footprint to degrade existing groundwater contamination (via reductive dechlorination) and stimulates long-term attenuation capacity in the distal plume (via cometabolism). For T-Area, the enhanced attenuation development

  13. "Enhanced" Ray Tracing Study of the Attenuation Lanes in Jupiter's Hectometric Radio Emission By Using Cassini Jupiter Encounter Data

    NASA Astrophysics Data System (ADS)

    Imai, M.; Lecacheux, A.

    2014-12-01

    Cassini Jupiter encounter, in the late 2000 and the early 2001, revealed persistent properties of Jovian hectometric (HOM) radiation, which is produced along auroral magnetic field lines in the polar regions of Jupiter. One of the unique properties - known as attenuation lanes (or so-called attenuation bands) - appears as a recurrent, well defined intensity extinction/enhancement feature in the HOM dynamic spectrum. It is believed that this phenomenon is the consequence of ray refraction from high-density medium - either (1) the field-aligned enhanced density along Io plasma torus or (2) Io plasma torus itself or both - in the course of radio propagation from the radio source to the observer. Many studies, mainly on case (1), have used standard ray-tracing technique, which cannot provide reliable information on transmitted radiation intensity. In this study, we have investigated case (2) by using an "enhanced" ray-tracing technique, in which a family of neighboring rays is simultaneously traced, allowing the physical intensity to be estimated along the ray path. We show the results of our ray-tracing computations and then suggest the most plausible scenario for the attenuation lanes phenomenon. More generally and from this example, we conclude that existing refracting plasma structures, encountered by radiation along its ray path through the planetary magnetosphere, might strongly affect, while not taken into account, the overall properties of the radio emission measured by a distant observer.

  14. Varenicline attenuates nicotine-enhanced brain-stimulation reward by activation of α4β2 nicotinic receptors in rats

    PubMed Central

    Spiller, Krista; Xi, Zheng-Xiong; Li, Xia; Ashby, Charles R.; Callahan, Patrick M.; Tehim, Ashok; Gardner, Eliot L.

    2009-01-01

    Varenicline, a partial α4β2 and full α7 nicotinic receptor agonist, has been shown to inhibit nicotine self-administration and nicotine-induced increases in extracellular dopamine in the nucleus accumbens. In the present study, we investigated whether varenicline inhibits nicotine-enhanced electrical brain-stimulation reward (BSR), and if so, which receptor subtypes are involved. Systemic administration of nicotine (0.25–1.0 mg/kg, i.p.) or varenicline (0.03–3 mg/kg, i.p.) produced biphasic effects, with low doses producing enhancement (e.g., decreased BSR threshold), and high doses inhibiting BSR. Pretreatment with low dose (0.03–1.0 mg/kg) varenicline dose-dependently attenuated nicotine (0.25 or 0.5 mg/kg)-enhanced BSR. The BSR-enhancing effect produced by varenicline was blocked by mecamylamine (a high affinity nicotinic receptor antagonist) or dihydro-β-erythroidine (a relatively selective nicotinic α4-containing receptor antagonist), but not methyllycaconitine (a selective α7 receptor antagonist), suggesting an effect mediated by activation of α4β2 receptors. This suggestion is supported by findings that the α4β2 receptor agonist SIB-1765F produced a dose-dependent enhancement of BSR, while pretreatment with SIB-1765F attenuated nicotine (0.5 mg/kg)-enhanced BSR. In contrast, the selective α7 receptor agonist ARR-17779, altered neither BSR itself nor nicotine-enhanced BSR, at any dose tested. These findings suggest that: 1) varenicline inhibits nicotine-enhanced BSR, supporting its use as a smoking cessation aid; and 2) varenicline-enhanced BSR by itself and varenicline's anti-nicotine effects are mediated by activation of α4β2, but not α7, receptors. PMID:19393252

  15. Neonatal handling (resilience) attenuates water-avoidance stress induced enhancement of chronic mechanical hyperalgesia in the rat

    PubMed Central

    Alvarez, Pedro; Levine, Jon D.; Green, Paul G.

    2015-01-01

    Chronic stress is well known to exacerbate pain. We tested the hypothesis that neonatal handling, which induces resilience to the negative impact of stress by increasing the quality and quantity of maternal care, attenuates the mechanical hyperalgesia produced by water-avoidance stress in the adult rat. Neonatal male rats underwent the handling protocol on postnatal days 2–9, weaned at 21 days and tested for muscle mechanical nociceptive threshold at postnatal days 50–75. Decrease in mechanical nociceptive threshold in skeletal muscle in adult rats, produced by exposure to water-avoidance stress, was significantly attenuated by neonatal handling. Neonatal handling also attenuated the mechanical hyperalgesia produced by intramuscular administration of the pronociceptive inflammatory mediator, prostaglandin E2 in rats exposed as adults to water-avoidance stress. Neonatal handling, which induces a smaller corticosterone response in adult rats exposed to a stressor as well as changes in central nervous system neurotransmitter systems, attenuates mechanical hyperalgesia produced by water-avoidance stress and enhanced prostaglandin hyperalgesia in adult animals. PMID:25637700

  16. Neonatal handling (resilience) attenuates water-avoidance stress induced enhancement of chronic mechanical hyperalgesia in the rat.

    PubMed

    Alvarez, Pedro; Levine, Jon D; Green, Paul G

    2015-03-30

    Chronic stress is well known to exacerbate pain. We tested the hypothesis that neonatal handling, which induces resilience to the negative impact of stress by increasing the quality and quantity of maternal care, attenuates the mechanical hyperalgesia produced by water-avoidance stress in the adult rat. Neonatal male rats underwent the handling protocol on postnatal days 2-9, weaned at 21 days and tested for muscle mechanical nociceptive threshold at postnatal days 50-75. Decrease in mechanical nociceptive threshold in skeletal muscle in adult rats, produced by exposure to water-avoidance stress, was significantly attenuated by neonatal handling. Neonatal handling also attenuated the mechanical hyperalgesia produced by intramuscular administration of the pronociceptive inflammatory mediator, prostaglandin E2 in rats exposed as adults to water-avoidance stress. Neonatal handling, which induces a smaller corticosterone response in adult rats exposed to a stressor as well as changes in central nervous system neurotransmitter systems, attenuates mechanical hyperalgesia produced by water-avoidance stress and enhanced prostaglandin hyperalgesia in adult animals. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Neural Correlates of Acquired Color Category Effects

    ERIC Educational Resources Information Center

    Clifford, Alexandra; Franklin, Anna; Holmes, Amanda; Drivonikou, Vicky G.; Ozgen, Emre; Davies, Ian R. L.

    2012-01-01

    Category training can induce category effects, whereby color discrimination of stimuli spanning a newly learned category boundary is enhanced relative to equivalently spaced stimuli from within the newly learned category (e.g., categorical perception). However, the underlying mechanisms of these acquired category effects are not fully understood.…

  18. Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin.

    PubMed

    Lee, Yoon Jae; Jang, Yo Han; Kim, Paul; Lee, Yun Ha; Lee, Young Jae; Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik; Seong, Baik Lin

    2016-04-01

    In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Importance of Contrast-Enhanced Fluid-Attenuated Inversion Recovery Magnetic Resonance Imaging in Various Intracranial Pathologic Conditions

    PubMed Central

    Lee, Eun Kyoung; Kim, Sungwon; Lee, Yong Seok

    2016-01-01

    Intracranial lesions may show contrast enhancement through various mechanisms that are closely associated with the disease process. The preferred magnetic resonance sequence in contrast imaging is T1-weighted imaging (T1WI) at most institutions. However, lesion enhancement is occasionally inconspicuous on T1WI. Although fluid-attenuated inversion recovery (FLAIR) sequences are commonly considered as T2-weighted imaging with dark cerebrospinal fluid, they also show mild T1-weighted contrast, which is responsible for the contrast enhancement. For several years, FLAIR imaging has been successfully incorporated as a routine sequence at our institution for contrast-enhanced (CE) brain imaging in detecting various intracranial diseases. In this pictorial essay, we describe and illustrate the diagnostic importance of CE-FLAIR imaging in various intracranial pathologic conditions. PMID:26798225

  20. Experimental study of the enhanced Raman scattering in the Sarid-type 4-layered attenuated total reflection configurations

    NASA Astrophysics Data System (ADS)

    Lee, Moon-Gyu; Lee, Jai-Hyung; Chang, Joon-Sung

    We experimentally explored the enhanced Raman scattering in pyridine (C 5H 5N) due to the excitation of long range surface plasmons (LRSP's) guided by a symmetrically bounded silver slab in the Sarid-type ATR (attenuated total reflection) configuration. We have observed that, with decreasing the metallic thickness, the absolute enhancement of the Raman cross section increases while the width of the polar angular distribution of the signal decreases. This observed dependence of the enhanced Raman intensity on the thickness of the thin Ag slab and the collecting solid angle is well explained by assuming that the Raman scattering is mediated by LRSP's. The observed maximum enhancement factor is 4 × 10 6 for the 140 Å silver slab which agrees well with the theoretically predicted value of 6 × 10 6.

  1. Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

    PubMed

    Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

    2015-01-01

    Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

  2. Enhancement of extinction learning attenuates ethanol-seeking behavior and alters plasticity in the prefrontal cortex.

    PubMed

    Gass, Justin T; Trantham-Davidson, Heather; Kassab, Amanda S; Glen, William B; Olive, M Foster; Chandler, L Judson

    2014-05-28

    Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfL cortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfL NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL calcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfL cortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity.

  3. Enhancement of Extinction Learning Attenuates Ethanol-Seeking Behavior and Alters Plasticity in the Prefrontal Cortex

    PubMed Central

    Trantham-Davidson, Heather; Kassab, Amanda S.; Glen, William B.; Olive, M. Foster; Chandler, L. Judson

    2014-01-01

    Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfL cortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfL NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL calcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfL cortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity. PMID:24872560

  4. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    SciTech Connect

    Barkhouse, Darryll A.; Faber, Milosz; Hooper, D. Craig

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression.

  5. Plasmid containing CpG motifs enhances the efficacy of porcine reproductive and respiratory syndrome live attenuated vaccine.

    PubMed

    Guo, Xiaoyu; Zhang, Quan; Hou, Shaohua; Zhai, Guoqin; Zhu, Hongfei; Sánchez-Vizcaíno, J M

    2011-12-15

    Porcine reproductive and respiratory syndrome (PRRS) is now among the most important swine diseases that affect the Chinese swine industry. Both killed and live attenuated vaccines are currently used against the disease, but neither of them could provide full protection after vaccination. In the present study, the adjuvanticity of a plasmid containing CpG motifs (pUC18-CpG) was introduced to enhance the efficacy of a commercial PRRS live attenuated vaccine. After vaccination, PRRSV-specific antibodies, PRRSV-specific cytokines, and clinical parameters were studied and compared between different vaccinated groups. During a following challenge study, co-administration of pUC18-CpG with the vaccine could confer higher protection rate. Our results have shown that co-administration of pUC18-CpG with the vaccine could elicit more potent adaptive immune response and provide better protection. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Enhanced efficacy of an attenuated Flavobacterium psychrophilum strain cultured under iron-limited conditions

    USDA-ARS?s Scientific Manuscript database

    An attenuated strain of Flavobacterium psychrophilum (CSF259-93B.17) has shown potential as a vaccine for prevention of bacterial coldwater disease (BCWD) in rainbow trout, Oncorhynchus mykiss (Walbaum). Because BCWD outbreaks can result in high mortality in other salmonid species, specifically coho...

  7. NEUROTROPHIN RECEPTOR BLOCKADE ATTENUATES DIESEL EXHAUST PARTICULATE MATTER (DEP) ENHANCEMENT OF ALLERGIC RESPONSES

    EPA Science Inventory

    ABSTRACT BODY:
    Recent investigations have linked neurotrophins including NGF, NT-3, and BDNF to allergic airways diseases. Antibody blockade of NGF attenuates airway resistance associated with allergic airway responses in mice. Mice administered an antibody against the low aff...

  8. NEUROTROPHIN RECEPTOR BLOCKADE ATTENUATES DIESEL EXHAUST PARTICULATE MATTER (DEP) ENHANCEMENT OF ALLERGIC RESPONSES

    EPA Science Inventory

    ABSTRACT BODY:
    Recent investigations have linked neurotrophins including NGF, NT-3, and BDNF to allergic airways diseases. Antibody blockade of NGF attenuates airway resistance associated with allergic airway responses in mice. Mice administered an antibody against the low aff...

  9. Colourful categories

    NASA Astrophysics Data System (ADS)

    Gromov, M. L.

    2015-08-01

    This paper presents Ramsey theory in category-theoretic terms as a message from a non-expert author to a non-expert reader. Everything is explained starting from the level zero, and an attempt is made to be as self-explanatory in the terminology and notation as possible. For the sake of references, the paper also reproduces traditional terminology, with concepts and theorems often named after (presumed) discoverers who are largely unknown to outsiders to the field. The sources are referred to in a manner so as to make them easy to find on the web; only exceptionally are non-freely accessible items referred to. Certain questions are formulated as 'conjectures', not out of a deep belief in their validity but because they sound better stated explicitly. There are no new results in this article, no deepening of particular aspects of Ramsey theory, no attempts to be comprehensive. But, in the spirit of the ideas of Anatoly Vershik, an attempt is made to move transversally across common directions of research, to see interrelations between them and to formulate questions. In fact, the article reproduces a chapter from the author's as yet unfinished manuscript "A number of questions". Bibliography: 65 titles.

  10. Dislocation Enhancement of Seismic-Frequency Attenuation: Subgrain Boundary Diffusion and Triggered, Critical Emission of Dislocations

    NASA Astrophysics Data System (ADS)

    Cooper, R. F.; McCarthy, C.

    2012-12-01

    Combined compressional creep and (Young's-modulus) attenuation experiments on polycrystalline ice-I (200 ≤ T[K] ≤ 260; 3 ≤ d[μm] ≤ 500; σmean = 1MPa and Δσ = 0.16MPa applied in a frequency range 10-4 ≤ ν[Hz] ≤ 10-1) demonstrate the attenuation behavior associated with the seismic attenuation band and the "high-temperature background," i.e., a power-law response Q-1 ∝ ν-m with m ~ 0.33. This response has, in general, been associated with grain boundary sliding rate-limited by atomic diffusion [e.g., 1-3], a mechanism that is very sensitive to grain size. In our experiments, however, with a grain size variation ~102, the attenuation response is independent of grain size, to first order. Scrutiny of the physics suggests that the attenuation is effected primarily by diffusive relaxation of subgrain boundaries [4, 5], the size of which, in materials deforming by a dislocation mechanism (as is the ice in our experiments), is set by the deviatoric stress [6, 7]. Applying the diffusion-effected physics to the subgrain size matches the universal scaling [e.g., 3] for materials that are linear-viscoelastic. Our ice specimens, however, demonstrate modest non-linearity, resulting in greater attenuation than that associated with the diffusion process [cf. 8] and yet retain the power-law form for attenuation, including the same slope m. The result is consistent with "self-organized critical" behavior in dislocation emission [9, 10] and the physics overall can be understood via models of self-similar scaling of crystalline (effective) viscosity [e.g., 11]. The potential application to seismic studies is profound: for example, if the upper mantle of Earth is convecting via a dislocation-creep or dislocation-accommodated grain-boundary-sliding mechanism, then the attenuation response is related not to the grain size, but rather to the subgrain structure associated with the creep of the rock. Thus, seismic attenuation measurements may well be useful for

  11. TREATABILITY STUDY FOR EDIBLE OIL DEPLOYMENT FOR ENHANCED CVOC ATTENUATION FOR T-AREA, SAVANNAH RIVER SITE

    SciTech Connect

    Riha, B.; Looney, B.; Noonkester, J.; Hyde, W.; Walker, R.

    2012-05-15

    Groundwater beneath T-Area, a former laboratory and semiworks operation at the Department of Energy (DOE) Savannah River Site (SRS), is contaminated by chlorinated solvents (cVOCs). Since the contamination was detected in the 1980s, the cVOCs at T-Area have been treated by a combination of soil vapor extraction and groundwater pump and treat. The site received approval to temporarily discontinue the active groundwater treatment and implement a treatability study of enhanced attenuation - an engineering and regulatory strategy that has recently been developed by DOE and the Interstate Technology and Regulatory Council (ITRC 2007). Enhanced attenuation uses active engineering solutions to alter the target site in such a way that the contaminant plume will passively stabilize and shrink and to document that the action will be effective, timely, and sustainable. The paradigm recognizes that attenuation remedies are fundamentally based on a mass balance. Thus, long-term plume dynamics can be altered either by reducing the contaminant loading from the source or by increasing the rate of natural attenuation processes within all, or part of, the plume volume. The combination of technologies that emerged for T-Area included: (1) neat (pure) vegetable oil deployment in the deep vadose zone in the former source area, (2) emulsified vegetable oil deployment within the footprint of the groundwater plume, and (3) identification of attenuation mechanisms and rates for the distal portion of the plume. In the first part, neat oil spreads laterally forming a thin layer on the water table to intercept and reduce future cVOC loading (via partitioning) and reduce oxygen inputs (via biostimulation). In the second and third parts, emulsified oil forms active bioremediation reactor zones within the plume footprint to degrade existing groundwater contamination (via reductive dechlorination and/or cometabolism) and stimulates long-term attenuation capacity in the distal plume (via

  12. Gamma-Glutamyl Cysteine Attenuates Tissue Damage and Enhances Tissue Regeneration in a rat Model of Lead-Induced Nephrotoxicity.

    PubMed

    Salama, Samir A; Arab, Hany H; Maghrabi, Ibrahim A; Hassan, Memy H; AlSaeed, Mohammed S

    2016-09-01

    Lead is a biohazardous metal that is commonly involved in human illness including renal injury. Although it is a non-redox reactive metal, lead-induced renal injury is largely based on oxidative stress. The current work aimed at exploring the possible protective effect of γ-glutamyl cysteine (γGC) against lead-induced renal injury. Rats were allocated to normal and γGC control groups, lead-treated group, and lead and γGC-treated group. γGC alleviated lead-induced renal injury as evidenced by attenuation of histopathological aberration, amelioration of oxidative injury as demonstrated by significant reduction in lipid and protein oxidation, elevation of total antioxidant capacity, and glutathione level. The activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) was significantly elevated. γGC significantly decreased levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β and the activity of the apoptotic marker caspase-3. In addition, γGC reduced kidney lead content, enhanced weight gain, and improved renal function as demonstrated by reduced serum levels of urea and creatinine. Importantly, γGC upregulated proliferating cell nuclear antigen (PCNA) expression, denoting enhanced renal regenerative capacity. Together, our findings highlight evidence for alleviating effects of γGC against lead-induced renal injury that is potentially mediated through diminution of oxidative tissue injury, reduction of inflammatory response, attenuation of apoptosis, and enhancement of renal regenerative capacity.

  13. Enhanced astroglial GABA uptake attenuates tonic GABAA inhibition of the presympathetic hypothalamic paraventricular nucleus neurons in heart failure.

    PubMed

    Pandit, Sudip; Jo, Ji Yoon; Lee, Sang Ung; Lee, Young Jae; Lee, So Yeong; Ryu, Pan Dong; Lee, Jung Un; Kim, Hyun-Woo; Jeon, Byeong Hwa; Park, Jin Bong

    2015-08-01

    γ-Aminobutyric acid (GABA) generates persistent tonic inhibitory currents (Itonic) and conventional inhibitory postsynaptic currents in the hypothalamic paraventricular nucleus (PVN) via activation of GABAA receptors (GABAARs). We investigated the pathophysiological significance of astroglial GABA uptake in the regulation of Itonic in the PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM). The Itonic of PVN-RVLM neurons were significantly reduced in heart failure (HF) compared with sham-operated (SHAM) rats. Reduced Itonic sensitivity to THIP argued for the decreased function of GABAAR δ subunits in HF, whereas similar Itonic sensitivity to benzodiazepines argued against the difference of γ2 subunit-containing GABAARs in SHAM and HF rats. HF Itonic attenuation was reversed by a nonselective GABA transporter (GAT) blocker (nipecotic acid, NPA) and a GAT-3 selective blocker, but not by a GAT-1 blocker, suggesting that astroglial GABA clearance increased in HF. Similar and minimal Itonic responses to bestrophin-1 blockade in SHAM and HF neurons further argued against a role for astroglial GABA release in HF Itonic attenuation. Finally, the NPA-induced inhibition of spontaneous firing was greater in HF than in SHAM PVN-RVLM neurons, whereas diazepam induced less inhibition of spontaneous firing in HF than in SHAM neurons. Overall, our results showed that combined with reduced GABAARs function, the enhanced astroglial GABA uptake-induced attenuation of Itonic in HF PVN-RVLM neurons explains the deficit in tonic GABAergic inhibition and increased sympathetic outflow from the PVN during heart failure.

  14. Enhanced oil production in a mature field assisted by spectral attenuation analysis

    NASA Astrophysics Data System (ADS)

    Ramírez-Cruz, Luis C.; del Valle-García, Raúl; Urrutia Fucugauchi, Jaime

    2005-03-01

    Seismic attenuation analysis is used to distinguish changes in the spectral and amplitude characteristics of the seismic signal with the purpose of identifying the presence of fluids and fractures within the rock system. The analysis of such changes can be used as a tool for characterizing rock properties and for understanding the behaviour of wave propagation in a complex environment comprised by pores and cracks containing fluids. The study is carried out using high-resolution reflection data obtained from a mature fractured carbonate reservoir near the northeast coast of Mexico. Production from this reservoir is declining considerably. For this reason, a horizontal drilling programme is being considered. The results obtained from in situ measurements indicate that spectral changes and attenuation anomalies are related to the presence of hydrocarbons in the fractured reservoir rocks; however, such anomalies are also related to wave scattering in highly fractured areas. The seismic attenuation patterns associated with the productive zones have helped to identify new potential areas and horizontal drilling targets.

  15. Cavitation-enhanced back projection for acoustic detection of attenuating structures

    NASA Astrophysics Data System (ADS)

    Ramaekers, Pascal; de Greef, Martijn; Moonen, Chrit T. W.; Ries, Mario

    2017-03-01

    Current methodology for the detection of attenuating structures in abdominal HIFU interventions requires lengthy, elaborate image analysis, which is undesired in a clinical setting. In this work, a method for the acoustic detection of attenuating structures in the beam path of the therapeutic HIFU array is described. The proposed method is used to determine binary apodizations that can be applied to the HIFU transducer for intercostal shot positions. Such a binary apodization was determined in vivo on an anesthetized pig under controlled breathing. Validation of the proposed method was done by comparing the binary apodization based on the proposed method to a binary apodization obtained using methodology based on MR image analysis and a collision detection algorithm. The proposed acoustical method provided a binary apodization that was over 90% similar to the apodization obtained using the image analysis-based method. Additionally, the proposed method can provide a measure of the amount of attenuation that each respective transducer element encounters in its beam path towards the focus.

  16. Attenuation of experimental colitis in glutathione peroxidase 1 and catalase double knockout mice through enhancing regulatory T cell function.

    PubMed

    Kim, Hyung-Ran; Lee, Anbok; Choi, Eun-Jeong; Kie, Jeong-Hae; Lim, Woosung; Lee, Hyeon Kook; Moon, Byung-In; Seoh, Ju-Young

    2014-01-01

    Reactive oxygen species (ROS) have been implicated in the progression of inflammatory diseases including inflammatory bowel diseases (IBD). Meanwhile, several studies suggested the protective role of ROS in immune-mediated inflammatory diseases, and it was recently reported that dextran sodium sulfate (DSS)-induced colitis was attenuated in mice with an elevated level of ROS due to deficiency of peroxiredoxin II. Regulatory T cells (Tregs) are critical in the prevention of IBD and Treg function was reported to be closely associated with ROS level, but it has been investigated only in lowered levels of ROS so far. In the present study, in order to clarify the relationship between ROS level and Treg function, and their role in the pathogenesis of IBD, we investigated mice with an elevated level of ROS due to deficiency of both glutathione peroxidase (GPx)-1 and catalase (Cat) for the susceptibility of DSS-induced colitis in association with Treg function. The results showed that DSS-induced colitis was attenuated and Tregs were hyperfunctional in GPx1-/- × Cat-/- mice. In vivo administration of N-acetylcysteine (NAC) aggravated DSS-induced colitis and decreased Treg function to the level comparable to WT mice. Attenuated Th17 cell differentiation from naïve CD4+ cells as well as impaired production of IL-6 and IL-17A by splenocytes upon stimulation suggested anti-inflammatory tendency of GPx1-/- × Cat-/- mice. Suppression of Stat3 activation in association with enhancement of indoleamine 2,3-dioxygenase and FoxP3 expression might be involved in the immunosuppressive mechanism of GPx1-/- × Cat-/- mice. Taken together, it is implied that ROS level is critical in the regulation of Treg function, and IBD may be attenuated in appropriately elevated levels of ROS.

  17. Dioscorea bulbifera polysaccharide and cyclophosphamide combination enhances anti-cervical cancer effect and attenuates immunosuppression and oxidative stress in mice.

    PubMed

    Cui, Hongxia; Li, Ting; Wang, Liping; Su, Yan; Xian, Cory J

    2016-01-12

    Cyclophosphamide (CTX) is commonly used in cancer chemotherapy, which causes immunosuppression and tissue oxidative stress at high doses. As potential protective agents, some polysaccharides were shown to have anti-tumor, anti-inflammatory and/or anti-oxidant properties. This study explored potential effects of oral treatment of Dioscorea bulbifera polysaccharides (DBLP at 100 or 150 mg/kg) in U14 cervical tumor-bearing mice treated with CTX (25 mg/kg). While CTX suppressed tumor growth (65.4% inhibition) and DBLP alone also inhibited tumor (25.6% at 100 mg/kg or 37.6% at 150 mg/kg), CTX+DBLP combination produced tumor inhibition rates of 5.6 (for 100 mg/kg DBLP) or 9% (for 150 mg/kg) higher than CTX alone. While tumor itself and CTX treatment reduced thymus and/or spleen/body weight indices, DBLP alone or CTX + DBLP combination attenuated this reduction. DBLP lowered peripheral blood T-cell subpopulation CD(4+)/CD(8+) ratio, and DBLP+CTX combination attenuated CTX effect in lifting CD(4+)/CD(8+) ratio. Tumor itself and CTX treatment heightened oxidative stress (with decreased superoxide dismutase but increased lactate dehydrogenase and malondialdehyde levels in serum and tissues), which was attenuated by DBLP treatment, and DBLP+CTX combination suppressed CTX-induced oxidative stress. Combination use of DBLP with CTX can potentially enhance CTX anti-tumor effect and can attenuate CTX-induced immunosuppression and oxidative stress in U14 cervical tumor-bearing mice.

  18. Dioscorea bulbifera polysaccharide and cyclophosphamide combination enhances anti-cervical cancer effect and attenuates immunosuppression and oxidative stress in mice

    PubMed Central

    Cui, Hongxia; Li, Ting; Wang, Liping; Su, Yan; Xian, Cory J.

    2016-01-01

    Cyclophosphamide (CTX) is commonly used in cancer chemotherapy, which causes immunosuppression and tissue oxidative stress at high doses. As potential protective agents, some polysaccharides were shown to have anti-tumor, anti-inflammatory and/or anti-oxidant properties. This study explored potential effects of oral treatment of Dioscorea bulbifera polysaccharides (DBLP at 100 or 150 mg/kg) in U14 cervical tumor-bearing mice treated with CTX (25 mg/kg). While CTX suppressed tumor growth (65.4% inhibition) and DBLP alone also inhibited tumor (25.6% at 100 mg/kg or 37.6% at 150 mg/kg), CTX+DBLP combination produced tumor inhibition rates of 5.6 (for 100 mg/kg DBLP) or 9% (for 150 mg/kg) higher than CTX alone. While tumor itself and CTX treatment reduced thymus and/or spleen/body weight indices, DBLP alone or CTX + DBLP combination attenuated this reduction. DBLP lowered peripheral blood T-cell subpopulation CD4+/CD8+ ratio, and DBLP+CTX combination attenuated CTX effect in lifting CD4+/CD8+ ratio. Tumor itself and CTX treatment heightened oxidative stress (with decreased superoxide dismutase but increased lactate dehydrogenase and malondialdehyde levels in serum and tissues), which was attenuated by DBLP treatment, and DBLP+CTX combination suppressed CTX-induced oxidative stress. Combination use of DBLP with CTX can potentially enhance CTX anti-tumor effect and can attenuate CTX-induced immunosuppression and oxidative stress in U14 cervical tumor-bearing mice. PMID:26753518

  19. Assessment of the effectiveness of onsite exsitu remediation by enhanced natural attenuation in the Niger Delta region, Nigeria.

    PubMed

    Okparanma, Reuben N; Azuazu, Ikeabiama; Ayotamuno, Josiah M

    2017-09-09

    This study was conducted to quantify and rank the effectiveness of onsite exsitu remediation by enhanced natural attenuation using soil quality index. The investigation was conducted at three oil spill sites in the Niger Delta (5.317°N, 6.467°E), Nigeria with a predominance of Oxisols. Baseline assessment and a two-step post-remediation monitoring of the sites were conducted. Target contaminants including total petroleum hydrocarbon (TPH) and BTEX (benzene, toluene, ethylbenzene, and xylene) were analyzed by gas chromatography-mass spectrometry. Results of the baseline assessment showed that TPH concentrations across the study sites averaged between 5113 and 7640 mg/kg at 0- to 1-m depth, which was higher than the local regulatory value of 5000 mg/kg. The soil quality index across the sites ranged between 68 and 45, suggesting medium to high potential ecological health risks with medium to high priority for remediation. BTEX concentrations followed a similar trend. However, after remediation TPH degraded rapidly initially and then slowly but asymptotically during the post-remediation monitoring period. Then, soil quality index across the study sites ranged between 100 and 58, indicating very low to medium potential ecological health risks. This demonstrates the effectiveness of onsite exsitu remediation by enhanced natural attenuation as a remediation strategy for petroleum-contaminated soils, which holds great promise for the Niger Delta province. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Characteristic MRI findings in hyperglycaemia-induced seizures: diagnostic value of contrast-enhanced fluid-attenuated inversion recovery imaging.

    PubMed

    Lee, E J; Kim, K K; Lee, E K; Lee, J E

    2016-12-01

    To describe characteristic magnetic resonance imaging (MRI) abnormalities in hyperglycaemia-induced seizures, and evaluate the diagnostic value of contrast-enhanced fluid-attenuated inversion recovery (FLAIR) imaging. Possible underlying mechanisms of this condition are also discussed. Eleven patients with hyperglycaemia-induced seizures and MRI abnormalities were retrospectively studied. Clinical manifestations, laboratory findings, MRI findings, and clinical outcomes were analysed. All patients, except one, presented with focal seizures, simple or complex partial seizures, or negative motor seizures. All patients had long-standing uncontrolled diabetes mellitus. The MRI abnormalities observed acutely were focal subcortical hypointensities on T2-weighted imaging and FLAIR imaging in all patients with overlying cortical gyral T2 hyperintensities in five. Focal overlying cortical or leptomeningeal enhancement on contrast-enhanced T1-weighted imaging or contrast-enhanced FLAIR imaging was observed in all patients. Contrast-enhanced FLAIR imaging was superior to contrast-enhanced T1-weighted imaging for detecting characteristic cortical or leptomeningeal enhancement. Diffusion-weighted imaging showed mildly restricted diffusion in four of five patients with cortical gyral T2 hyperintensity. In nine patients, the lesions were localised in the parietal or parieto-occipital lobes. The other two patients showed localised precentral gyral lesions. After treatment, the neurological symptoms, including the seizures, improved in all patients. On clinical recovery, the subcortical T2 hypointensity, gyral or leptomeningeal enhancement, and overlying cortical T2 hyperintensities resolved. Recognition of these radiological abnormalities in patients with hyperglycaemia-induced seizures is important in restricting unwarranted investigations and initiating early therapy. These patients generally have a good prognosis. Copyright © 2016 The Royal College of Radiologists. Published by

  1. Natural and Enhanced Attenuation of Chlorinated Solvents Using RT3D

    SciTech Connect

    Johnson, Christian D.; Truex, Michael J.; Clement, T P.

    2006-07-25

    RT3D (Reactive Transport in 3-Dimensions) is a reactive transport code that can be applied to model solute fate and transport for many different purposes. This document specifically addresses application of RT3D for modeling related to evaluation and implementation of Monitored Natural Attenuation (MNA). Selection of MNA as a remedy requires an evaluation process to demonstrate that MNA will meet the remediation goals. The U.S. EPA, through the Office of Solid Waste and Emergency Response (OSWER) Directive 9200.4?17P, provides the regulatory context for the evaluation and implementation of MNA. In a complementary fashion, the context for using fate and transport modeling as part of MNA evaluation is described in the EPA?s technical protocol for chlorinated solvent MNA, the Scenarios Evaluation Tool for Chlorinated Solvent MNA, and in this document. The intent of this document is to describe (1) the context for applying RT3D for chlorinated solvent MNA and (2) the attenuation processes represented in RT3D, (3) dechlorination reactions that may occur, and (4) the general approach for using RT3D reaction modules (including a summary of the RT3D reaction modules that are available) to model fate and transport of chlorinated solvents as part of MNA or for combinations of MNA and selected types of active remediation.

  2. Intensity noise enhancement in the half-wave plate/polarizer attenuator.

    PubMed

    Kolner, B H

    1991-06-01

    The conventional optical attenuator for linearly polarized light is usually constructed with a half-wave retardation plate and a polarizer. With one axis of the polarizer aligned so as to transmit the incident beam fully, the addition of the half-wave plate causes the output power to follow a cos(2) 2theta dependence, where theta is the angle between the optic axis of the wave plate and the incident polarization. When the incident light has an additional orthogonal polarization component, the output power dependence becomes more complex and depends on the correlation between the two polarization fields ?E(x)E(y)?. More significantly, if amplitude noise in the polarization fields is correlated, the attenuator will couple the noise processes, which results in relative power fluctuations that increase as the optical power is reduced. The noise produced by this coupling may even exceed the noise of either polarization state alone. Measurements of the statistical behavior of the relative intensity noise of a cw modelocked Nd:YAG laser as a function of the wave-plate angle showed more than a tenfold increase when the output power was reduced to near minimum. In addition, the noise was found to be asymmetrical about the minimum power point, theta = 45 degrees . It is shown that the simple addition of a polarizer ahead of the wave plate strips off the unwanted polarization field and virtually eliminates this added noise effect.

  3. Fisetin enhances behavioral performances and attenuates reactive gliosis and inflammation during aluminum chloride-induced neurotoxicity.

    PubMed

    Prakash, Dharmalingam; Gopinath, Kulasekaran; Sudhandiran, Ganapasam

    2013-03-01

    Aluminum (Al) is an environmental neurotoxin that affects cerebral functions and causes health complications. However, the role of Al in arbitrating glia homeostasis and pathophysiology remains obscure. Astrocyte, microglia activation (reactive gliosis), and associated inflammatory events play a decisive role in neurodegeneration and may represent a target for treating neurodegenerative disorders. In this study, we have analyzed the role of aluminum chloride (AlCl3) in causing reactive gliosis in the brain of mice and the ability of fisetin, a flavonoid to attenuate reactive gliosis and neuronal inflammation. Reports suggest that fisetin exerts antioxidant and anti-inflammatory actions. Fisetin at a dose of 15 mg/kg body weight was orally administered, daily (pre-treated for 4 weeks before AlCl3 induction and co-treated until experimental period of 8 weeks) to mice induced with AlCl3 (200 mg/kg b.wt./day/8 weeks, orally). Administration of AlCl3 developed behavioral deficits, triggered lipid peroxidation (LPO), compromised acetylcholine esterase (AChE) activity, and reduced the levels of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and reduced glutathione (GSH), and caused histologic aberrations. These effects were accompanied by increased expressions of Glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1. Pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1β, inducible nitric oxide synthase, were increased upon AlCl3 administration. AlCl3-induced alterations in the activities of SOD, CAT, GST, AChE and levels of GSH, LPO, activity of AChE, behavioral deficits, histologic aberrations, reactive gliosis, and inflammatory niche were attenuated on treatment with fisetin. Collectively, our results indicate that fisetin exerts neuroprotection against AlCl3-induced brain pathology.

  4. Diminazene aceturate enhances ACE2 activity and attenuates ischemia-induced cardiac pathophysiology

    PubMed Central

    Qi, YanFei; Zhang, Juan; Cole-Jeffrey, Colleen T; Shenoy, Vinayak; Espejo, Andrew; Hanna, Mina; Song, Chunjuan; Pepine, Carl J; Katovich, Michael J; Raizada, Mohan K

    2013-01-01

    Angiotensin-converting enzyme 2 (ACE2) plays a critical role against myocardial infarction (MI). We hypothesized that activation of intrinsic ACE2 would be protective against ischemia-induced cardiac pathophysiology. Diminazine aceturate (DIZE), a small molecule ACE2 activator has been used to evaluate this hypothesis. DIZE (15 mg/kg/day, s.c.) was injected two days prior to MI surgery and continued throughout the study-period. MI rats showed a 62% decrease in fractional shortening (FS,%) [control (Con): 51.1 ± 3.2; DIZE alone (D) : 52.1 ± 3.2; MI (M): 19.1± 3.0], a 55% decrease in contractility (dP/dtmax mmHg/s) (Con: 9480 ± 425.3; D: 9585 ± 597.4; M: 4251 ± 657.7), and a 27% increase in ventricular hypertrophy [VH, mg/mm (Con: 26.5 ± 1.5; D: 26.9 ± 1.4; M: 33.4± 1.1)]. DIZE attenuated the MI-induced decrease in FS by 89%, improved dP/dtmax by 92%, and reversed VH by 18%. MI also significantly increased ACE and angiotensin type 1 receptor levels while decreased ACE2 activity by 40% (Con: 246.2 ± 25.1; D: 254.2 ± 20.6; M: 148.9 ± 29.2, RFU/min), which was reversed by DIZE treatment. Thus, DIZE treatment decreased the infarct area, attenuated LV remodeling post-MI and restored normal balance of the cardiac renin angiotensin system. Additionally, DIZE treatment increased circulating endothelial progenitor cells, increased engraftment of cardiac progenitor cells and decreased inflammatory cells in peri-infarct cardiac regions. All of the beneficial effects associated with DIZE treatment were abolished by C-16, an ACE2 inhibitor. Collectively, DIZE and DIZE-like small molecules may represent promising new therapeutic agents for MI. PMID:23959549

  5. Absence of Protoheme IX Farnesyltransferase CtaB Causes Virulence Attenuation but Enhances Pigment Production and Persister Survival in MRSA.

    PubMed

    Xu, Tao; Han, Jian; Zhang, Jia; Chen, Jiazhen; Wu, Nan; Zhang, Wenhong; Zhang, Ying

    2016-01-01

    The membrane protein CtaB in S. aureus is a protoheme IX farnesyltransferase involved in the synthesis of the heme containing terminal oxidases of bacterial respiratory chain. In this study, to assess the role of CtaB in S. aureus virulence, pigment production, and persister formation, we constructed a ctaB mutant in the methicillin-resistant Staphylococcus aureus (MRSA) strain USA500. We found that deletion of ctaB attenuated growth and virulence in mice but enhanced pigment production and formation of quinolone tolerant persister cells in stationary phase. RNA-seq analysis showed that deletion of ctaB caused decreased transcription of several virulence genes including RNAIII which is consistent with its virulence attenuation. In addition, transcription of 20 ribosomal genes and 24 genes involved in amino acid biosynthesis was significantly down-regulated in the ctaB knockout mutant compared with the parent strain. These findings suggest the importance of heme biosynthesis in virulence and persister formation of S. aureus.

  6. Absence of Protoheme IX Farnesyltransferase CtaB Causes Virulence Attenuation but Enhances Pigment Production and Persister Survival in MRSA

    PubMed Central

    Xu, Tao; Han, Jian; Zhang, Jia; Chen, Jiazhen; Wu, Nan; Zhang, Wenhong; Zhang, Ying

    2016-01-01

    The membrane protein CtaB in S. aureus is a protoheme IX farnesyltransferase involved in the synthesis of the heme containing terminal oxidases of bacterial respiratory chain. In this study, to assess the role of CtaB in S. aureus virulence, pigment production, and persister formation, we constructed a ctaB mutant in the methicillin-resistant Staphylococcus aureus (MRSA) strain USA500. We found that deletion of ctaB attenuated growth and virulence in mice but enhanced pigment production and formation of quinolone tolerant persister cells in stationary phase. RNA-seq analysis showed that deletion of ctaB caused decreased transcription of several virulence genes including RNAIII which is consistent with its virulence attenuation. In addition, transcription of 20 ribosomal genes and 24 genes involved in amino acid biosynthesis was significantly down-regulated in the ctaB knockout mutant compared with the parent strain. These findings suggest the importance of heme biosynthesis in virulence and persister formation of S. aureus. PMID:27822202

  7. β-Integrin de-phosphorylation by the Density-Enhanced Phosphatase DEP-1 attenuates EGFR signaling in C. elegans

    PubMed Central

    Umbricht, Christoph Alois; Fröhli, Erika

    2017-01-01

    Density-Enhanced Phosphatase-1 (DEP-1) de-phosphorylates various growth factor receptors and adhesion proteins to regulate cell proliferation, adhesion and migration. Moreover, dep-1/scc1 mutations have been detected in various types of human cancers, indicating a broad tumor suppressor activity. During C. elegans development, DEP-1 mediates binary cell fate decisions by negatively regulating EGFR signaling. Using a substrate-trapping DEP-1 mutant in a proteomics approach, we have identified the C. elegans β-integrin subunit PAT-3 as a specific DEP-1 substrate. DEP-1 selectively de-phosphorylates tyrosine 792 in the membrane-proximal NPXY motif to promote integrin activation via talin recruitment. The non-phosphorylatable β-integrin mutant pat-3(Y792F) partially suppresses the hyperactive EGFR signaling phenotype caused by loss of dep-1 function. Thus, DEP-1 attenuates EGFR signaling in part by de-phosphorylating Y792 in the β-integrin cytoplasmic tail, besides the direct de-phosphorylation of the EGFR. Furthermore, in vivo FRAP analysis indicates that the αβ-integrin/talin complex attenuates EGFR signaling by restricting receptor mobility on the basolateral plasma membrane. We propose that DEP-1 regulates EGFR signaling via two parallel mechanisms, by direct receptor de-phosphorylation and by restricting receptor mobility through αβ-integrin activation. PMID:28135265

  8. Infection-enhancing lipopeptides do not improve intranasal immunization of cotton rats with a delta-G candidate live-attenuated human respiratory syncytial virus vaccine.

    PubMed

    Tien Nguyen, D; Boes, Jolande; van Amerongen, Geert; van Remmerden, Yvonne; Yüksel, Selma; Guichelaar, Teun; Osterhaus, Albert D M E; de Swart, Rik L

    2013-12-01

    Development of live-attenuated human respiratory syncytial virus (HRSV) vaccines has proven to be difficult. Several vaccine candidates were found to be over-attenuated and displayed limited immunogenicity. Recently, we identified three synthetic cationic lipopeptides that enhanced paramyxovirus infections in vitro. The infection enhancement proved to be mediated by enhanced virus binding to target cells. We hypothesized that these lipopeptides can be used as adjuvants to promote immune responses induced by live-attenuated paramyxovirus vaccines. This hypothesis was tested in a vaccination and challenge model in cotton rats, using a previously described recombinant live-attenuated candidate HRSV vaccine lacking the gene encoding the G glycoprotein (rHRSVΔG). Surprisingly, intranasal vaccination of cotton rats with rHRSVΔG formulated in infection-enhancing lipopeptides resulted in reduced virus loads in nasopharyngeal lavages, reduced seroconversion levels and reduced protection from wild-type HRSV challenge. In conclusion, we were unable to demonstrate the feasibility of lipopeptides as adjuvants for a candidate live-attenuated HRSV vaccine in the cotton rat model.

  9. Does phosphate enhance the natural attenuation of crude oil in groundwater under defined redox conditions?

    PubMed

    Ponsin, Violaine; Mouloubou, Olsen Raïnness; Prudent, Pascale; Höhener, Patrick

    2014-11-15

    After a crude oil spill caused by a broken pipeline in 2009 to a gravel aquifer in southern France, degradation processes under various redox conditions progressively established, but at rates that predict a long life-time of the source under natural attenuation after partial source removal. In this study, we aimed at identifying the rate-limiting factors for each redox condition, with special emphasis on phosphate as limiting nutrient. The study was conducted in laboratory microcosms assembled with material collected on site: sediments, water from monitoring wells, oil and microbial sludge. Redox conditions were promoted by adding electron acceptors (either oxygen, nitrate, limonite (FeO(OH)), cryptomelane (K(Mn(4+),Mn(2+))8O16), or sulfate). For each condition, the role of phosphate was studied by repeated additions for up to 290days. The results showed a very strong stimulation of aerobic and denitrifying rates of oil degradation by phosphate, provided that oxygen and nitrate were repeatedly supplied. Phosphate caused also a marked stimulation of methanogenic degradation, and a relatively small stimulation of metal reduction. These anaerobic processes started only after marked lag phases, and phosphate shortened the lag phase for methanogenic degradation. Degradation of aromatic and aliphatic hydrocarbons with less than 8 carbons, including benzene, was confirmed even under unstimulated conditions. It is concluded that degradation rates at the site are limited by both, availability of electron acceptors and availability of phosphate needed for promoting microbial growth. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Dietary Supplementation of Blueberry Juice Enhances Hepatic Expression of Metallothionein and Attenuates Liver Fibrosis in Rats

    PubMed Central

    Wang, Yuping; Cheng, Mingliang; Zhang, Baofang; Nie, Fei; Jiang, Hongmei

    2013-01-01

    Aim To investigate the effect of blueberry juice intake on rat liver fibrosis and its influence on hepatic antioxidant defense. Methods Rabbiteye blueberry was used to prepare fresh juice to feed rats by daily gastric gavage. Dan-shao-hua-xian capsule (DSHX) was used as a positive control for liver fibrosis protection. Liver fibrosis was induced in male Sprague-Dawley rats by subcutaneous injection of CCl4 and feeding a high-lipid/low-protein diet for 8 weeks. Hepatic fibrosis was evaluated by Masson staining. The expression of α-smooth muscle actin (α-SMA) and collagen III (Col III) were determined by immunohistochemical techniques. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenates were determined. Metallothionein (MT) expression was detected by real-time RT-PCR and immunohistochemical techniques. Results Blueberry juice consumption significantly attenuates CCl4-induced rat hepatic fibrosis, which was associated with elevated expression of metallothionein (MT), increased SOD activity, reduced oxidative stress, and decreased levels of α-SMA and Col III in the liver. Conclusion Our study suggests that dietary supplementation of blueberry juice can augment antioxidative capability of the liver presumably via stimulating MT expression and SOD activity, which in turn promotes HSC inactivation and thus decreases extracellular matrix collagen accumulation in the liver, and thereby alleviating hepatic fibrosis. PMID:23554912

  11. Inhibition of N-terminal ATPase on HSP90 attenuates colitis through enhanced Treg function.

    PubMed

    Collins, C B; Aherne, C M; Yeckes, A; Pound, K; Eltzschig, H K; Jedlicka, P; de Zoeten, E F

    2013-09-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory condition thought to reflect a failure of the enteral immune system to adequately regulate itself. Inflammatory stress drives upregulation of heat-shock proteins (HSPs), including the pro-inflammatory chaperone, HSP90. This protein sequesters the transcription factor, heat-shock factor 1 (HSF1) in the cytoplasm preventing transcription of a number of anti-inflammatory proteins. We hypothesized that inhibition of HSP90 would exert an anti-inflammatory effect and thereby attenuate intestinal inflammation in murine models of IBD. Inhibition of HSP90 with 17-allylaminogeldanamycin (17-AAG) reduced inflammation in acute dextran sodium sulfate and chronic CD45RB(High) colitis models coinciding with increased interleukin (IL)-10 production in the colon. Regulatory T cells (Tregs) from mice treated with 17-AAG demonstrated significantly greater suppressive capacity in vitro abolished in HSF1-/- or IL-10-/- cells. Finally, Tregs treated with 17-AAG exhibited increased nuclear localization of HSF1 with resultant upregulation of HSF1 response genes, including HSP70, HSP90 and IL-10.

  12. SA 4503 attenuates cocaine-induced hyperactivity and enhances methamphetamine substitution for a cocaine discriminative stimulus.

    PubMed

    Rodvelt, Kelli R; Lever, Susan Z; Lever, John R; Blount, Lucas R; Fan, Kuo-Hsien; Miller, Dennis K

    2011-02-01

    Cocaine exhibits preferential (~15-fold) affinity for σ₁ over σ₂ sigma receptors, and previous research has shown an interaction of σ₁ receptor-selective ligands and cocaine's behavioral effects. The present study investigated the effect of the putative sigma receptor agonist SA 4503 (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride) on cocaine's locomotor stimulatory and discriminative stimulus properties. At doses without intrinsic activity, SA 4503 dose-dependently attenuated cocaine-induced hyperactivity in mice. This inhibition was overcome by increasing the cocaine dose. In rats trained to use cocaine as a discriminative stimulus in a drug discrimination task, doses of SA 4503 that did not substitute for the cocaine stimulus did not alter the cocaine substitution curve. However, SA 4503 potentiated the effect of methamphetamine to substitute for the cocaine stimulus. These data support a role for sigma receptors in the locomotor-activating properties of cocaine and, importantly, indicate a role for these receptors in the discriminative stimulus effects of methamphetamine. The data also suggest sigma receptors mediate the activity of different dopamine pathways responsible for the behavioral effects of psychostimulants.

  13. Does phosphate enhance the natural attenuation of crude oil in groundwater under defined redox conditions?

    NASA Astrophysics Data System (ADS)

    Ponsin, Violaine; Mouloubou, Olsen Raïnness; Prudent, Pascale; Höhener, Patrick

    2014-11-01

    After a crude oil spill caused by a broken pipeline in 2009 to a gravel aquifer in southern France, degradation processes under various redox conditions progressively established, but at rates that predict a long life-time of the source under natural attenuation after partial source removal. In this study, we aimed at identifying the rate-limiting factors for each redox condition, with special emphasis on phosphate as limiting nutrient. The study was conducted in laboratory microcosms assembled with material collected on site: sediments, water from monitoring wells, oil and microbial sludge. Redox conditions were promoted by adding electron acceptors (either oxygen, nitrate, limonite (FeO(OH)), cryptomelane (K(Mn4 +,Mn2 +)8O16), or sulfate). For each condition, the role of phosphate was studied by repeated additions for up to 290 days. The results showed a very strong stimulation of aerobic and denitrifying rates of oil degradation by phosphate, provided that oxygen and nitrate were repeatedly supplied. Phosphate caused also a marked stimulation of methanogenic degradation, and a relatively small stimulation of metal reduction. These anaerobic processes started only after marked lag phases, and phosphate shortened the lag phase for methanogenic degradation. Degradation of aromatic and aliphatic hydrocarbons with less than 8 carbons, including benzene, was confirmed even under unstimulated conditions. It is concluded that degradation rates at the site are limited by both, availability of electron acceptors and availability of phosphate needed for promoting microbial growth.

  14. Peripheral neuron plasticity is enhanced by brief electrical stimulation and overrides attenuated regrowth in experimental diabetes.

    PubMed

    Singh, B; Krishnan, A; Micu, I; Koshy, K; Singh, V; Martinez, J A; Koshy, D; Xu, F; Chandrasekhar, A; Dalton, C; Syed, N; Stys, P K; Zochodne, D W

    2015-11-01

    Peripheral nerve regrowth is less robust than commonly assumed, particularly when it accompanies common clinical scenarios such as diabetes mellitus. Brief extracellular electrical stimulation (ES) facilitates the regeneration of peripheral nerves in part through early activation of the conditioning injury response and BDNF. Here, we explored intrinsic neuronal responses to ES to identify whether ES might impact experimental diabetes, where regeneration is attenuated. ES altered several regeneration related molecules including rises in tubulin, Shh (Sonic hedgehog) and GAP43 mRNAs. ES was associated with rises in neuronal intracellular calcium but its strict linkage to regrowth was not confirmed. In contrast, we identified PI3K-PTEN involvement, an association previously linked to diabetic regenerative impairment. Following ES there were declines in PTEN protein and mRNA both in vitro and in vivo and a PI3K inhibitor blocked its action. In vitro, isolated diabetic neurons were capable of mounting robust responsiveness to ES. In vivo, ES improved electrophysiological and behavioral indices of nerve regrowth in a chronic diabetic model of mice with pre-existing neuropathy. Regrowth of myelinated axons and reinnervation of the epidermis were greater following ES than sham stimulation. Taken together, these findings identify a role for ES in supporting regeneration during the challenges of diabetes mellitus.

  15. Enhancing survival motor neuron expression extends lifespan and attenuates neurodegeneration in mutant TDP-43 mice.

    PubMed

    Perera, Nirma D; Sheean, Rebecca K; Crouch, Peter J; White, Anthony R; Horne, Malcolm K; Turner, Bradley J

    2016-09-15

    Defects in the RNA-binding proteins survival motor neuron (SMN) and TAR DNA-binding protein 43 (TDP-43) cause progressive motor neuron degeneration in spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), respectively. While low levels of SMN protein in motor neurons result in SMA, recent studies implicate abnormal SMN levels and function in ALS pathogenesis. Here, we determine that SMN protein is upregulated early and progressively in spinal and cortical motor neurons of male transgenic mutant TDP-43(A315T) mice. Cytoplasmic SMN aggregates that contain TDP-43 and HuR were identified in motor neurons of TDP-43(A315T) mice, consistent with the incorporation of SMN into stress granules. To test the impact of augmenting SMN levels in TDP-43 proteinopathy, we demonstrate that neuronal overexpression of human SMN in TDP-43(A315T) mice delayed symptom onset and prolonged survival. SMN upregulation also countered motor neuron degeneration, attenuated activation of astrocytes and microglia and restored AMP kinase activation in spinal cords of TDP-43(A315T) mice. We also reveal that expression of another factor conferring motor neuron vulnerability, androgen receptor (AR), is reduced in spinal cords of male TDP-43(A315T) mice. These results establish that SMN overexpression in motor neurons slows disease onset and outcome by ameliorating pathological signs in this model of mutant TDP-43-mediated ALS. Further approaches to augment SMN levels using pharmacological or gene therapy agents may therefore be warranted in ALS. Our data also reinforce a novel potential link between ALS and spinal bulbar muscular atrophy (SBMA), another motor neurodegenerative disease mediated by reduced AR function in motor neurons. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Enhanced Phosphatase Activity Attenuates α-Synucleinopathy in a Mouse Model

    PubMed Central

    Lee, Kang-Woo; Chen, Walter; Junn, Eunsung; Im, Joo-Young; Grosso, Hilary; Sonsalla, Patricia K.; Feng, Xuyan; Ray, Neelanjana; Fernandez, Jose R.; Chao, Yang; Masliah, Eliezer; Voronkov, Michael; Braithwaite, Steven P.; Stock, Jeffry B.; Mouradian, M. Maral

    2016-01-01

    α-Synuclein (α-Syn) is a key protein that accumulates as hyperphosphorylated aggregates in pathologic hallmark features of Parkinson’s disease (PD) and other neurodegenerative disorders. Phosphorylation of this protein at serine 129 is believed to promote its aggregation and neurotoxicity suggesting that this post-translational modification could be a therapeutic target. Here, we demonstrate that protein phosphatase 2A (PP2A) dephosphorylates α-Syn at serine 129, and that this activity is greatly enhanced by carboxyl methylation of the catalytic C subunit of PP2A. α-Syn transgenic mice raised on a diet supplemented with eicosinoyl-5-hydroxytryptamide (EHT), an agent that enhances PP2A methylation, dramatically reduced both α-Syn phosphorylation at Serine 129 and α-Syn aggregation in the brain. These biochemical changes were associated with enhanced neuronal activity, increased dendritic arborizations, reduced astroglial and microglial activation, as well as improved motor performance. These findings support the notion that serine 129 phosphorylation of α-Syn is of pathogenetic significance, and that promoting PP2A activity is a viable disease modifying therapeutic strategy for α-synucleinopathies such as PD. PMID:21562258

  17. L-serine supplementation attenuates alcoholic fatty liver by enhancing homocysteine metabolism in mice and rats.

    PubMed

    Sim, Woo-Cheol; Yin, Hu-Quan; Choi, Ho-Sung; Choi, You-Jin; Kwak, Hui Chan; Kim, Sang-Kyum; Lee, Byung-Hoon

    2015-02-01

    Hyperhomocysteinemia plays an important role in the development of hepatic steatosis, and studies indicate that homocysteine-lowering treatment inhibits the development of fatty liver. We evaluated the effects of L-serine on alcoholic fatty liver and homocysteine metabolism. In a binge ethanol study, male C57BL/6 mice were divided into 4 groups: control, ethanol + vehicle, and ethanol + 20 or 200 mg/kg L-serine. Mice were gavaged with ethanol (5 g/kg body weight) 3 times every 12 h with or without L-serine which was given twice 30 min before the last 2 ethanol doses. Control mice were fed isocaloric dextran-maltose. In a chronic ethanol study, male Wistar rats were divided into 3 groups: control, ethanol, and ethanol + L-serine. Rats were fed a standard Lieber-DeCarli ethanol diet (36% ethanol-derived calories) for 4 wk with or without dietary L-serine supplementation (1%; wt:vol) for the last 2 wk. In control rats, the ethanol-derived calories were replaced with dextran-maltose. The effects of L-serine were also tested in AML12 cells manipulated to have high homocysteine concentrations by silencing the genes involved in homocysteine metabolism. Binge ethanol treatment increased serum homocysteine and hepatic triglyceride (TG) concentrations by >5-fold vs. controls, which were attenuated in the 200-mg/kg L-serine treatment group by 60.0% and 47.5%, respectively, compared with the ethanol group. In the chronic ethanol study, L-serine also decreased hepatic neutral lipid accumulation by 63.3% compared with the ethanol group. L-serine increased glutathione and S-adenosylmethionine by 94.0% and 30.6%, respectively, compared with the ethanol group. Silencing betaine homocysteine methyltransferase, cystathionine β-synthase, or methionine increased intracellular homocysteine and TG concentrations by >2-fold, which was reversed by L-serine when L-serine-independent betaine homocysteine methyltransferase was knocked down. These results demonstrate that L-serine ameliorates

  18. Dichloroacetate blocks aerobic glycolytic adaptation to attenuated measles virus and promotes viral replication leading to enhanced oncolysis in glioblastoma

    PubMed Central

    Su, Lei; Chen, Aiping; Xia, Mao; Xu, Chun; Yu, Decai; Jiang, Aiqin; Wei, Jiwu

    2015-01-01

    Targeting reprogrammed energy metabolism such as aerobic glycolysis is a potential strategy for cancer treatment. However, tumors exhibiting low-rate glycolysis or metabolic heterogeneity might be resistant to such treatment. We hypothesized that a therapeutic modality that drove cancer cells to high-rate glycolysis might sensitize cancer cells to interference directed against metabolic flux. In this study, we found that attenuated oncolytic measles virus Edmonston strain (MV-Edm) caused glioblastoma cells to shift to high-rate aerobic glycolysis; this adaptation was blocked by dichloroacetate (DCA), an inhibitor of glycolysis, leading to profound cell death of cancer cells but not of normal cells. DCA enhanced viral replication by mitigating mitochondrial antiviral signaling protein (MAVS)-mediated innate immune responses. In a subcutaneous glioblastoma (GBM) xenograft mouse model, low-dose MV-Edm and DCA significantly inhibited tumor growth in vivo. We found that DCA impaired glycolysis (blocking bioenergetic generation) and enhanced viral replication (increasing bioenergetic consumption), which, in combination, accelerated bioenergetic exhaustion leading to necrotic cell death. Taken together, oncolytic MV-Edm sensitized cancer cells to DCA, and in parallel, DCA promoted viral replication, thus, improving oncolysis. This novel therapeutic approach should be readily incorporated into clinical trials. PMID:25575816

  19. Enhanced defense against mitochondrial hydrogen peroxide attenuates age-associated cognition decline.

    PubMed

    Chen, Liuji; Na, Ren; Ran, Qitao

    2014-11-01

    Increased mitochondrial hydrogen peroxide (H2O2) is associated with Alzheimer's disease and brain aging. Peroxiredoxin 3 (Prdx3) is the key mitochondrial antioxidant defense enzyme in detoxifying H2O2. To investigate the importance of mitochondrial H2O2 in age-associated cognitive decline, we compared cognition between aged (17-19 months) APP transgenic mice and APP/Prdx3 double transgenic mice (dTG) and between old (24 months) wild-type mice and Prdx3 transgenic mice (TG). Compared with aged APP mice, aged dTG mice showed improved cognition that was correlated with reduced brain amyloid beta levels and decreased amyloid beta production. Old TG mice also showed significantly increased cognitive ability compared with old wild-type mice. Both aged dTG mice and old TG mice had reduced mitochondrial oxidative stress and increased mitochondrial function. Moreover, CREB signaling, a signaling pathway important for cognition was enhanced in both aged dTG mice and old TG mice. Thus, our results indicate that mitochondrial H2O2 is a key culprit of age-associated cognitive impairment, and that a reduction of mitochondrial H2O2 could improve cognition by maintaining mitochondrial health and enhancing CREB signaling. Published by Elsevier Inc.

  20. Dichloroacetate Enhances Apoptotic Cell Death via Oxidative Damage and Attenuates Lactate Production in Metformin-Treated Breast Cancer Cells

    PubMed Central

    Haugrud, Allison B.; Zhuang, Yongxian; Coppock, Joseph D.; Miskimins, W. Keith

    2014-01-01

    Purpose The unique metabolism of breast cancer cells provides interest in exploiting this phenomenon therapeutically. Metformin, a promising breast cancer therapeutic, targets complex I of the electron transport chain leading to an accumulation of reactive oxygen species (ROS) that eventually lead to cell death. Inhibition of complex I leads to lactate production, a metabolic byproduct already highly produced by reprogrammed cancer cells and associated with a poor prognosis. While metformin remains a promising cancer therapeutic, we sought a complementary agent to increase apoptotic promoting effects of metformin while attenuating lactate production possibly leading to greatly improve efficacy. Dichloroacetate (DCA) is a well-established drug used in the treatment of lactic acidosis which functions through inhibition of pyruvate dehydrogenase kinase (PDK) promoting mitochondrial metabolism. Our purpose was to examine the synergy and mechanisms by which these two drugs kill breast cancer cells. Methods Cell lines were subjected to the indicated treatments and analyzed for cell death and various aspects of metabolism. Cell death and ROS production was analyzed using flow cytometry, Western blot analysis, and cell counting methods. Images of cells were taken with phase contrast microscopy or confocal microscopy. Metabolism of cells was analyzed using the Seahorse XF24 analyzer, lactate assays, and pH analysis. Results We show that when DCA and metformin are used in combination, synergistic induction of apoptosis of breast cancer cells occurs. Metformin-induced oxidative damage is enhanced by DCA through PDK1 inhibition which also diminishes metformin promoted lactate production. Conclusions We demonstrate that DCA and metformin combine to synergistically induce caspase-dependent apoptosis involving oxidative damage with simultaneous attenuation of metformin promoted lactate production. Innovative combinations such as metformin and DCA show promise in expanding breast

  1. Metformin exerts glucose-lowering action in high-fat fed mice via attenuating endotoxemia and enhancing insulin signaling.

    PubMed

    Zhou, Zi-Yu; Ren, Li-Wei; Zhan, Ping; Yang, Han-Yan; Chai, Dan-Dan; Yu, Zhi-Wen

    2016-08-01

    Accumulating evidence shows that lipopolysaccharides (LPS) derived from gut gram-negative bacteria can be absorbed, leading to endotoxemia that triggers systemic inflammation and insulin resistance. In this study we examined whether metformin attenuated endotoxemia, thus improving insulin signaling in high-fat diet fed mice. Mice were fed a high-fat diet for 18 weeks to induce insulin resistance. One group of the mice was treated with oral metformin (100 mg·kg(-1)·d(-1)) for 4 weeks. Another group was treated with LPS (50 μg·kg(-1)·d(-1), sc) for 5 days followed by the oral metformin for 10 d. Other two groups received a combination of antibiotics for 7 d or a combination of antibiotics for 7 d followed by the oral metformin for 4 weeks, respectively. Glucose metabolism and insulin signaling in liver and muscle were evaluated, the abundance of gut bacteria, gut permeability and serum LPS levels were measured. In high-fat fed mice, metformin restored the tight junction protein occludin-1 levels in gut, reversed the elevated gut permeability and serum LPS levels, and increased the abundance of beneficial bacteria Lactobacillus and Akkermansia muciniphila. Metformin also increased PKB Ser473 and AMPK T172 phosphorylation, decreased MDA contents and redox-sensitive PTEN protein levels, activated the anti-oxidative Nrf2 system, and increased IκBα in liver and muscle of the mice. Treatment with exogenous LPS abolished the beneficial effects of metformin on glucose metabolism, insulin signaling and oxidative stress in liver and muscle of the mice. Treatment with antibiotics alone produced similar effects as metformin did. Furthermore, the beneficial effects of antibiotics were addictive to those of metformin. Metformin administration attenuates endotoxemia and enhances insulin signaling in high-fat fed mice, which contributes to its anti-diabetic effects.

  2. Attenuation of the posttranslational oscillator via transcription-translation feedback enhances circadian-phase shifts in Synechococcus.

    PubMed

    Hosokawa, Norimune; Kushige, Hiroko; Iwasaki, Hideo

    2013-08-27

    Circadian rhythms are endogenous biological timing processes that are ubiquitous in organisms ranging from cyanobacteria to humans. In the photoautotrophic unicellular cyanobacterium Synechococcus elongatus PCC 7942, under continuous light (LL) conditions, the transcription-translation feedback loop (TTFL) of KaiC generates a rhythmic change in the accumulation of KaiC relative to KaiA clock proteins (KaiC/KaiA ratio), which peak and trough at subjective dawn and dusk, respectively. However, the role of TTFL in the cyanobacterial circadian system remains unclear because it is not an essential requirement for the basic oscillation driven by the Kai-based posttranslational oscillator (PTO) and the transcriptional output mechanisms. Here, we show that TTFL is important for the circadian photic resetting property in Synechococcus. The robustness of PTO, which is exemplified by the amplitude of the KaiC phosphorylation cycle, changed depending on the KaiC/KaiA ratio, which was cyclic under LL. After cells were transferred from LL to the dark, the clock protein levels remained constant in the dark. When cells were transferred from LL to continuous dark at subjective dawn, the KaiC phosphorylation cycle was attenuated with a lower KaiC/KaiA ratio, a higher KaiC phosphorylation level, and a lower amplitude than that in cells transferred at subjective dusk. We also found that the greater the degree to which PTO was attenuated in continuous dark, the greater the phase shifts upon the subsequent light exposure. Based on these results, we propose that TTFL enhances resetting of the Kai-based PTO in Synechococcus.

  3. Natural and Enhanced Attenuation of Soil and Groundwater at the Monument Valley, Arizona, DOE Legacy Waste Site—10281

    SciTech Connect

    Waugh, W.J.; Miller, D.E.; Morris, S.A.; Sheader, L.R.; Glenn, E.P.; Moore, D.; Carroll, K.C.; Benally, L.; Roanhorse, M.; Bush, R.P.; none,

    2010-03-07

    The U.S. Department of Energy (DOE), the Navajo Nation, and the University of Arizona are exploring natural and enhanced attenuation remedies for groundwater contamination at a former uranium-ore processing site near Monument Valley, Arizona. DOE removed radioactive tailings from the Monument Valley site in 1994. Nitrate and ammonium, waste products of the milling process, remain in an alluvial groundwater plume spreading from the soil source where tailings were removed. Planting and irrigating two native shrubs, fourwing saltbush and black greasewood, markedly reduced both nitrate and ammonium in the source area over an 8-year period. Total nitrogen dropped from 350 mg/kg in 2000 to less than 200 mg/kg in 2008. Most of the reduction is attributable to irrigation-enhanced microbial denitrification rather than plant uptake. However, soil moisture and percolation flux monitoring show that the plantings control the soil water balance in the source area, preventing additional leaching of nitrogen compounds. Enhanced denitrification and phytoremediation also look promising for plume remediation. Microcosm experiments, nitrogen isotopic fractionation analysis, and solute transport modeling results suggest that (1) up to 70 percent of nitrate in the plume has been lost through natural denitrification since the mill was closed in 1968, and (2) injection of ethanol may accelerate microbial denitrification in plume hot spots. A field-scale ethanol injection pilot study is underway. Landscape-scale remote sensing methods developed for the project suggest that transpiration from restored native phreatophyte populations rooted in the aquifer could limit further expansion of the plume. An evaluation of landfarm phytoremediation, the irrigation of native shrub plantings with high nitrate water pumped from the alluvial aquifer, is also underway.

  4. Cell-Associated Flagella Enhance the Protection Conferred by Mucosally-Administered Attenuated Salmonella Paratyphi A Vaccines

    PubMed Central

    Gat, Orit; Galen, James E.; Tennant, Sharon; Simon, Raphael; Blackwelder, William C.; Silverman, David J.; Pasetti, Marcela F.; Levine, Myron M.

    2011-01-01

    Background Antibiotic-resistant Salmonella enterica serovar Paratyphi A, the agent of paratyphoid A fever, poses an emerging public health dilemma in endemic areas of Asia and among travelers, as there is no licensed vaccine. Integral to our efforts to develop a S. Paratyphi A vaccine, we addressed the role of flagella as a potential protective antigen by comparing cell-associated flagella with exported flagellin subunits expressed by attenuated strains. Methodology S. Paratyphi A strain ATCC 9150 was first deleted for the chromosomal guaBA locus, creating CVD 1901. Further chromosomal deletions in fliD (CVD 1901D) or flgK (CVD 1901K) were then engineered, resulting in the export of unpolymerized FliC, without impairing its overall expression. The virulence of the resulting isogenic strains was examined using a novel mouse LD50 model to accommodate the human-host restricted S. Paratyphi A. The immunogenicity of the attenuated strains was then tested using a mouse intranasal model, followed by intraperitoneal challenge with wildtype ATCC 9150. Results Mucosal (intranasal) immunization of mice with strain CVD 1901 expressing cell-associated flagella conferred superior protection (vaccine efficacy [VE], 90%) against a lethal intraperitoneal challenge, compared with the flagellin monomer-exporting mutants CVD 1901K (30% VE) or CVD 1901D (47% VE). The superior protection induced by CVD 1901 with its cell-attached flagella was associated with an increased IgG2a∶IgG1 ratio of FliC-specific antibodies with enhanced opsonophagocytic capacity. Conclusions Our results clearly suggest that enhanced anti-FliC antibody-mediated clearance of S. Paratyphi A by phagocytic cells, induced by vaccines expressing cell-associated rather than exported FliC, might be contributing to the vaccine-induced protection from S. Paratyphi A challenge in vivo. We speculate that an excess of IgG1 anti-FliC antibodies induced by the exported FliC may compete with the IgG2a subtype and block

  5. Selective Homocysteine Lowering Gene Transfer Improves Infarct Healing, Attenuates Remodelling, and Enhances Diastolic Function after Myocardial Infarction in Mice

    PubMed Central

    Singh, Neha; Gordts, Stephanie C.; De Geest, Bart

    2013-01-01

    Background and aims Homocysteine levels predict heart failure incidence in prospective epidemiological studies and correlate with severity of heart failure in cross-sectional surveys. The objective of this study was to evaluate whether a selective homocysteine lowering intervention beneficially affects cardiac remodelling and cardiac function after myocardial infarction (MI) in a murine model of combined hypercholesterolemia and hyperhomocysteinemia. Methodology and principal findings A selective homocysteine lowering gene transfer strategy was evaluated in female C57BL/6 low density lipoprotein receptor (Ldlr)−/− cystathionine-ß-synthase (Cbs)+/− deficient mice fed a hyperhomocysteinemic and high saturated fat/high cholesterol diet using an E1E3E4-deleted hepatocyte-specific adenoviral vector expressing Cbs (AdCBS). MI was induced by permanent ligation of the left anterior descending coronary artery 14 days after saline injection or gene transfer. AdCBS gene transfer resulted in a persistent more than 5-fold (p<0.01) decrease of plasma homocysteine levels and significantly improved endothelial progenitor cell function. Selective homocysteine lowering enhanced infarct healing as indicated by a 21% (p<0.01) reduction of infarct length at day 28 after MI and by an increased number of capillaries and increased collagen content in the infarct zone. Adverse remodelling was attenuated in AdCBS MI mice as evidenced by a 29% (p<0.05) reduction of left ventricular cavity area at day 28, by an increased capillary density in the remote myocardium, and by reduced interstitial collagen. The peak rate of isovolumetric relaxation was increased by 19% (p<0.05) and the time constant of left ventricular relaxation was reduced by 21% (p<0.05) in AdCBS MI mice compared to control MI mice, indicating improved diastolic function. Conclusion/significance Selective homocysteine lowering gene transfer improves infarct healing, attenuates remodelling, and significantly enhances

  6. Iron-enhanced coagulation is attenuated by chelation: thrombelastographic and ultrastructural analysis.

    PubMed

    Nielsen, Vance G; Pretorius, Etheresia

    2014-12-01

    Increased circulating ferritin and free iron have been found in a variety of disease states associated with thrombophilia. When blood or plasma is exposed to iron addition, characteristic changes in thrombus formation are observed by scanning electron microscopy, which include fusion of fibrin polymers, matting, and even sheeting of fibrin. A primary mechanism posited to explain iron-mediated hypercoagulability is hydroxyl radical formation and modification of fibrinogen; however, iron has also been demonstrated to bind to fibrinogen. We have recently demonstrated that iron enhances coagulation, manifested as a decrease in the time of onset of coagulation. Using clinically encountered concentrations of iron created by addition of FeCl3 to human plasma, we demonstrated that iron-mediated changes in reaction time determined by thrombelastography or changes in thrombus ultrastructure were significantly, but not completely, reversed by iron chelation with deferoxamine. Thus, reversible iron binding to fibrinogen mechanistically explains a significant portion of coagulation kinetic and ultrastructural hypercoagulability. Further investigation is needed to determine whether residual iron binding or other iron-mediated effects is responsible for hypercoagulability observed after chelation.

  7. Berberine enhances antidiabetic effects and attenuates untoward effects of canagliflozin in streptozotocin-induced diabetic mice.

    PubMed

    Tian, Cai-Ming; Jiang, Xin; Ouyang, Xiao-Xi; Zhang, Ya-Ou; Xie, Wei-Dong

    2016-07-01

    The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduced, and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated. Our results showed that berberine combined with canagliflozin (BC) increased reduction of fasting and postprandial blood glucose, diet, and water intake compared with berberine or canagliflozin alone. Interestingly, BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone. In addition, BC showed increased phosphorylated 5' AMP-activated protein kinase (pAMPK) expression and decreased tumor necrosis factor alpha (TNFα) levels in kidneys, compared with berberine or canagliflozin alone. These results indicated that BC was a stronger antidiabetic than berberine or canagliflozin alone with less negative side effects on the kidneys in the diabetic mice. The antidiabetic effect was likely to be mediated by synergically promoting the expression of pAMPK and reducing the expression of TNFα in kidneys. The present study represented the first report that canagliflozin combined with berberine was a promising treatment for diabetes mellitus. The exact underlying mechanisms of action should be investigated in future studies.

  8. Interleukin 36α Attenuates Sepsis by Enhancing Antibacterial Functions of Macrophages.

    PubMed

    Tao, Xintong; Song, Zhixin; Wang, Chuanjiang; Luo, Hongchun; Luo, Qin; Lin, Xue; Zhang, Liping; Yin, Yibing; Cao, Ju

    2017-01-15

    Sepsis is newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality rate and limited effective treatments. The role of interleukin 36α (IL-36α) in host response during sepsis remains unknown. An experimental sepsis model of cecal ligation and puncture was established to investigate the effects of IL-36α on host response to sepsis. IL-36α production was significantly up-regulated during sepsis. IL-36α treatment reduced the mortality rate in mice with severe sepsis by cecal ligation and puncture. IL-36α-treated mice had more efficient bacterial clearance, inhibited tissue inflammation, improved organ injury, and reduced immune cell apoptosis. The therapeutic implication of these observations was also highlighted by the finding that specific blockade of IL-36α led to an increased mortality rate in mice with nonsevere sepsis. Furthermore, we found that IL-36α enhanced bacterial phagocytosis and killing by macrophages, thereby allowing local and systemic bacterial clearance. Importantly, macrophage depletion before the onset of sepsis eliminated IL-36α-mediated protection against sepsis. Our results demonstrate that IL-36α plays an important role in the host defense response to sepsis and suggest a potential therapeutic role for IL-36α in sepsis.

  9. Natural attenuation is enhanced in previously contaminated and coniferous forest soils.

    PubMed

    Kauppi, Sari; Romantschuk, Martin; Strömmer, Rauni; Sinkkonen, Aki

    2012-01-01

    Prevalence of organic pollutants or their natural analogs in soil is often assumed to lead to adaptation in the bacterial community, which results in enhanced bioremediation if the soil is later contaminated. In this study, the effects of soil type and contamination history on diesel oil degradation and bacterial adaptation were studied. Mesocosms of mineral and organic forest soil (humus) were artificially treated with diesel oil, and oil hydrocarbon concentrations (GC-FID), bacterial community composition (denaturing gradient gel electrophoresis, DGGE), and oil hydrocarbon degraders (DGGE + sequencing of 16S rRNA genes) were monitored for 20 weeks at 16°C. Degradation was advanced in previously contaminated soils as compared with pristine soils and in coniferous organic forest soil as compared with mineral soil. Contamination affected bacterial community composition especially in the pristine mineral soil, where diesel addition increased the number of strong bands in the DGGE gel. Sequencing of cloned 16S rRNA gene fragments and DGGE bands showed that potential oil-degrading bacteria were found in mineral and organic soils and in both pristine and previously contaminated mesocosms. Fast oil degradation was not associated with the presence of any particular bacterial strain in soil. We demonstrate at the mesocosm scale that previously contaminated and coniferous organic soils are superior environments for fast oil degradation as compared with pristine and mineral soil environments. These results may be utilized in preventing soil pollution and planning soil remediation.

  10. Exosomes derived from endothelial progenitor cells attenuate vascular repair and accelerate reendothelialization by enhancing endothelial function.

    PubMed

    Li, Xiaocong; Chen, Chunyuan; Wei, Liming; Li, Qing; Niu, Xin; Xu, Yanjun; Wang, Yang; Zhao, Jungong

    2016-02-01

    Exosomes, a key component of cell paracrine secretion, can exert protective effects in various disease models. However, application of exosomes in vascular repair and regeneration has rarely been reported. In this study, we tested whether endothelial progenitor cell (EPC)-derived exosomes possessed therapeutic effects in rat models of balloon-induced vascular injury by accelerating reendothelialization. Exosomes were obtained from the conditioned media of EPCs isolated from human umbilical cord blood. Induction of the endothelial injury was performed in the rats' carotid artery, and the pro-re-endothelialization capacity of EPC-derived exosomes was measured. The in vitro effects of exosomes on the proliferation and migration of endothelial cells were investigated. We found that the EPC-derived exosomes accelerated the re-endothelialization in the early phase after endothelial damage in the rat carotid artery. We also demonstrated that these exosomes enhanced the proliferation and migration of endothelial cells in vitro. Moreover, endothelial cells stimulated with these exosomes showed increased expression of angiogenesis-related molecules. Taken together, our results indicate that exosomes are an active component of the paracrine secretion of human EPCs and can promote vascular repair in rat models of balloon injury by up-regulating endothelial cells function. Copyright © 2015. Published by Elsevier Inc.

  11. Octreotide Attenuates Acute Kidney Injury after Hepatic Ischemia and Reperfusion by Enhancing Autophagy

    PubMed Central

    Sun, Huiping; Zou, Shuangfa; Candiotti, Keith A.; Peng, Yanhua; Zhang, Qinya; Xiao, Weiqiang; Wen, Yiyun; wu, Jiao; Yang, Jinfeng

    2017-01-01

    Octreotide exerts a protective effect in hepatic ischemia-reperfusion (HIR) injury. However, whether octreotide preconditioning could also reduce acute kidney injury (AKI) after HIR is unknown. This study was designed to investigate the role of octreotide in AKI after HIR. Male Sprague-Dawley rats were pretreated with octreotide or octreotide combined with 3-methyladenine (autophagy inhibitor, 3MA). Plasma creatinine, inflammation markers (e.g., TNF-α and IL-6 etc.), apoptosis, autophagy and phosphorylation of protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase (Akt/mTOR/p70S6K) in the kidney were measured after 60 minutes of liver ischemia and 24 hours of reperfusion for each rat. Octreotide pretreatment significantly preserved renal function and reduced the severity of renal injury. Moreover, octreotide alleviated inflammation and apoptosis in the kidney after HIR. Additionally, octreotide induced autophagy and autophagy inhibition with 3MA markedly reversed the renoprotective, anti-inflammatory and anti-apoptotic effects of octreotide after HIR. Finally, octreotide abrogated the activation of phosphorylation of Akt, mTOR and p70S6K in the kidney after HIR. Our results indicate that octreotide reduced renal injury after HIR due to its induction of autophagy. The enhancement of autophagy may be potentially linked to the octreotide mediated Akt/mTOR/p70S6K pathway deactivation and reduction of kidney inflammation and apoptosis after HIR. PMID:28205545

  12. Source treatment and barriers using ORC{reg_sign} to enhance natural attenuation

    SciTech Connect

    Koenigsberg, S.S.; Sandefur, C.A.

    1996-12-31

    ORC is a unique formulation of magnesium peroxide that releases oxygen slowly when hydrated. The compound is insoluble and releases oxygen while being converted to ordinary magnesium hydroxide which is also insoluble. ORC is packaged in exchangeable filter socks and is contacted with contaminated groundwater via an array of wells or trenches. ORC can also be made into a slurry to create permanent implants in the saturated zone, or dispersed as a free powder for the in-situ or ex-situ treatment of soil. These methods enhance the intrinsic bioremediation of aerobically degradable compounds and are summarized. ORC mediated oxygenated zones generally last four months to a year as a function of contaminant flux. The objective of the oxygen barrier is plume cut-off, however, any significant reduction of contaminant mass will reduce risk. A broad array of treatment points, in which ORC is backfilled or injected, can be effective for low-level source treatment. The points can be implemented with low-cost, small-bore technologies to achieve full remediation or risk reduction objectives. An overview of the history of the environmental applications of ORC, and the evolution of the strategies for site closure involving direct treatment of contaminants sources and control of plume migration, will be the emphasis of this presentation.

  13. [PPARα attenuates palmitate-induced endoplasmic reticulum stress in human cardiac cells by enhancing AMPK activity].

    PubMed

    Palomer, Xavier; Capdevila-Busquets, Eva; Garreta, Gerard; Davidson, Mercy M; Vázquez-Carrera, Manuel

    2014-01-01

    Endoplasmic reticulum (ER) stress has been linked to several cardiovascular diseases, such as atherosclerosis, heart failure and cardiac hypertrophy. ER stress impairs insulin signalling, thus contributing to the development of insulin resistance and diabetes. Since several studies have reported that PPARα may inhibit ER stress, the main aim of this study consisted in investigating whether activation of this nuclear receptor is able to prevent lipid-induced ER stress in cardiac cells, as well as studying the mechanisms involved. A cardiomyocyte cell line of human origin, AC16, was treated with palmitate in the presence or absence of several AMPK and PPARα pharmacological agonists and antagonists. For the in vivo studies, wild-type male mice were fed a standard diet, or a high-fat diet (HFD), for two months. At the end of the experiments, several ER stress markers were assessed in cardiac cells or in the mice hearts, using real-time RT-PCR and Western-blot analyses. The results demonstrate that both palmitate and the HFD induced ER stress in cardiac cells, since they upregulated the expression (ATF3, BiP/GRP78 and CHOP), splicing (sXBP1), and phosphorylation (IRE-1α and eIF2α) of several ER stress markers. Interestingly, treatment with the PPARα agonist Wy-14,643 prevented an increase in the majority of these ER stress markers in human cardiac cells by means of AMPK activation. These data indicate that PPARα activation by Wy-14,643 might be useful to prevent the harmful effects of ER stress and associated cardiovascular diseases in obese patients, and even during diabetic cardiomyopathy, by enhancing AMPK activity. Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  14. Ellagic acid enhances morphine analgesia and attenuates the development of morphine tolerance and dependence in mice.

    PubMed

    Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Ghorbanzadeh, Behnam

    2014-10-15

    According to our previous study, ellagic acid has both dose-related central and peripheral antinociceptive effect through the opioidergic and l-arginine-NO-cGMP-ATP sensitive K(+) channel pathways. In the present study, the systemic antinociceptive effects of ellagic acid in animal models of pain, and functional interactions between ellagic acid and morphine in terms of analgesia, tolerance and dependence were investigated. Ellagic acid (1-30mg/kg; i.p.) showed significant and dose-dependent antinociceptive effects in the acetic acid-induced writhing test. Intraperitoneal ellagic acid acutely interacted with morphine analgesia in a synergistic manner in this assay. Ellagic acid (1-10mg/kg; i.p.) also exerted analgesic activity in the hot-plate test. Pre-treatment with naloxone (1mg/kg; i.p.) significantly reversed ellagic acid, morphine as well as ellagic acid-morphine combination-induced antinociceptin in these two tests. More importantly, when co-administered with morphine, ellagic acid (1-10mg/kg) effectively blocked the development of tolerance to morphine analgesia in the hot-plate test. Likewise, ellagic acid dose-dependently prevented naloxone-precipitated withdrawal signs including jumping and weight loss. Ellagic acid treatment (1-30mg/kg; i.p.) had no significant effect on the locomotion activity of animals using open-field task. Therefore, these results showed that ellagic acid has notable systemic antinociceptive activity for both tonic and phasic pain models. Altogether, ellagic acid might be used in pain relief alone or in combination with opioid drugs because of enhancing morphine analgesia and preventing morphine-induced tolerance to analgesia and dependence. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Generation and preclinical evaluation of a DENV-1/2 prM+E chimeric live attenuated vaccine candidate with enhanced prM cleavage.

    PubMed

    Keelapang, Poonsook; Nitatpattana, Narong; Suphatrakul, Amporn; Punyahathaikul, Surat; Sriburi, Rungtawan; Pulmanausahakul, Rojjanaporn; Pichyangkul, Sathit; Malasit, Prida; Yoksan, Sutee; Sittisombut, Nopporn

    2013-10-17

    In the absence of a vaccine or sustainable vector control measures, illnesses caused by dengue virus infection remain an important public health problem in many tropical countries. During the export of dengue virus particles, furin-mediated cleavage of the prM envelope protein is usually incomplete, thus generating a mixture of immature, partially mature and mature extracellular particles. Variations in the arrangement and conformation of the envelope proteins among these particles may be associated with their different roles in shaping the antibody response. In an attempt to improve upon live, attenuated dengue vaccine approaches, a mutant chimeric virus, with enhanced prM cleavage, was generated by introducing a cleavage-enhancing substitution into a chimeric DENV-1/2 virus genome, encoding the prM+E sequence of a recent DENV-1 isolate under an attenuated DENV-2 genetic background. A modest increase in virus specific infectivity observed in the mutant chimeric virus affected neither the attenuation phenotype, when assessed in the suckling mouse neurovirulence model, nor multiplication in mosquitoes. The two chimeric viruses induced similar levels of anti-DENV-1 neutralizing antibody response in mice and rhesus macaques, but more efficient control of viremia during viral challenge was observed in macaques immunized with the mutant chimeric virus. These results indicate that the DENV-1/2 chimeric virus, with enhanced prM cleavage, could be useful as an alternative live, attenuated vaccine candidate for further tests in humans.

  16. Saikokeishito Extract Exerts a Therapeutic Effect on alpha-Naphthylisothiocyanate-Induced Liver Injury in Rats through Attenuation of Enhanced Neutrophil Infiltration and Oxidative Stress in the Liver Tissue.

    PubMed

    Ohta, Yoshiji; Kongo-Nishimura, Mutsumi; Hayashi, Takahiro; Kitagawa, Akira; Matsura, Tatsuya; Yamada, Kazuo

    2007-01-01

    We examined whether Saikokeishito extract (TJ-10), a traditional Japanese herbal medicine, exerts a therapeutic effect on alpha-naphthylisothiocyanate (ANIT)-induced liver injury in rats through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue. In rats treated once with ANIT (75 mg/kg, i.p.), liver injury with cholestasis occurred 24 h after treatment and progressed at 48 h. When ANIT-treated rats orally received TJ-10 (0.26, 1.3 or 2.6 g/kg) at 24 h after the treatment, progressive liver injury with cholestasis was significantly attenuated at 48 h after the treatment at the dose of 1.3 or 2.6 g/kg. At 24 h after ANIT treatment, increases in hepatic lipid peroxide and reduced glutathione contents and myeloperoxidase activity occurred with decreases in hepatic superoxide dismutase and glutathione reductase activities. At 48 h after ANIT treatment, these changes except for reduced glutathione were enhanced with decreases in catalase, Se-glutathione peroxidase, and glucose-6-phosphate dehydrogenase activities. TJ-10 (1.3 or 2.6 g/kg) post-administered to ANIT-treated rats attenuated these changes found at 48 h after the treatment significantly. These results indicate that TJ-10 exerts a therapeutic effect on ANIT-induced liver injury in rats possibly through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue.

  17. Microbial respiration and natural attenuation of benzene contaminated soils investigated by cavity enhanced Raman multi-gas spectroscopy.

    PubMed

    Jochum, Tobias; Michalzik, Beate; Bachmann, Anne; Popp, Jürgen; Frosch, Torsten

    2015-05-07

    Soil and groundwater contamination with benzene can cause serious environmental damage. However, many soil microorganisms are capable to adapt and are known to strongly control the fate of organic contamination. Innovative cavity enhanced Raman multi-gas spectroscopy (CERS) was applied to investigate the short-term response of the soil micro-flora to sudden surface contamination with benzene regarding the temporal variations of gas products and their exchange rates with the adjacent atmosphere. (13)C-labeled benzene was spiked on a silty-loamy soil column in order to track and separate the changes in heterotrophic soil respiration - involving (12)CO2 and O2- from the natural attenuation process of benzene degradation to ultimately form (13)CO2. The respiratory quotient (RQ) decreased from a value 0.98 to 0.46 directly after the spiking and increased again within 33 hours to a value of 0.72. This coincided with the maximum (13)CO2 concentration rate (0.63 μmol m(-2) s(-1)), indicating the highest benzene degradation at 33 hours after the spiking event. The diffusion of benzene in the headspace and the biodegradation into (13)CO2 were simultaneously monitored and 12 days after the benzene spiking no measurable degradation was detected anymore. The RQ finally returned to a value of 0.96 demonstrating the reestablished aerobic respiration.

  18. Taurine attenuates hippocampal and corpus callosum damage, and enhances neurological recovery after closed head injury in rats.

    PubMed

    Gu, Y; Zhao, Y; Qian, K; Sun, M

    2015-04-16

    The protective effects of taurine against closed head injury (CHI) have been reported. This study was designed to investigate whether taurine reduced white matter damage and hippocampal neuronal death through suppressing calpain activation after CHI in rats. Taurine (50 mg/kg) was administered intravenously 30 min and 4 h again after CHI. It was found that taurine lessened the corpus callosum damage, attenuated the neuronal cell death in hippocampal CA1 and CA3 subfields and improved the neurological functions 7 days after CHI. Moreover, it suppressed the over-activation of calpain, enhanced the levels of calpastatin, and reduced the degradation of neurofilament heavy protein, myelin basic protein and αII-spectrin in traumatic tissue 24 h after CHI. These data confirm the protective effects of taurine against gray and white matter damage due to CHI, and suggest that down-regulating calpain activation could be one of the protective mechanisms of taurine against CHI. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Enhancement of Gastric Ulcer Healing and Angiogenesis by Hepatocyte Growth Factor Gene Mediated by Attenuated Salmonella in Rats.

    PubMed

    Ha, Xiaoqin; Peng, Junhua; Zhao, Hongbin; Deng, Zhiyun; Dong, Juzi; Fan, Hongyan; Zhao, Yong; Li, Bing; Feng, Qiangsheng; Yang, Zhihua

    2017-02-01

    The present study developed an oral hepatocyte growth factor (HGF) gene therapy strategy for gastric ulcers treatment. An attenuated Salmonella typhimurium that stably expressed high HGF (named as TPH) was constructed, and the antiulcerogenic effect of TPH was evaluated in a rat model of gastric ulcers that created by acetic acid subserosal injection. From day 5 after injection, TPH (1 × 10⁹ cfu), vehicle (TP, 1 × 10⁹ cfu), or sodium bicarbonate (model control) was administered orally every alternate day for three times. Then ulcer size was measured at day 21 after ulcer induction. The ulcer area in TPH-treated group was 10.56 ± 3.30 mm², which was smaller when compared with those in the TP-treated and model control groups (43.47 ± 4.18 and 56.25 ± 6.38 mm², respectively). A higher level of reepithelialization was found in TPH-treated group and the crawling length of gastric epithelial cells was significantly longer than in the other two groups (P < 0.05). The microvessel density in the ulcer granulation tissues of the TPH-treated rats was 39.9 vessels/mm², which was greater than in the TP-treated and model control rats, with a significant statistical difference. These results suggest that TPH treatment significantly accelerates the healing of gastric ulcers via stimulating proliferation of gastric epithelial cells and enhancing angiogenesis on gastric ulcer site.

  20. AAV8-Mediated In Vivo Overexpression of miR-155 Enhances the Protective Capacity of Genetically Attenuated Malarial Parasites

    PubMed Central

    Hentzschel, Franziska; Hammerschmidt-Kamper, Christiane; Börner, Kathleen; Heiss, Kirsten; Knapp, Bettina; Sattler, Julia M; Kaderali, Lars; Castoldi, Mirco; Bindman, Julia G; Malato, Yann; Willenbring, Holger; Mueller, Ann-Kristin; Grimm, Dirk

    2014-01-01

    Malaria, caused by protozoan Plasmodium parasites, remains a prevalent infectious human disease due to the lack of an efficient and safe vaccine. This is directly related to the persisting gaps in our understanding of the parasite's interactions with the infected host, especially during the clinically silent yet essential liver stage of Plasmodium development. Previously, we and others showed that genetically attenuated parasites (GAP) that arrest in the liver induce sterile immunity, but only upon multiple administrations. Here, we comprehensively studied hepatic gene and miRNA expression in GAP-injected mice, and found both a broad activation of IFNγ-associated pathways and a significant increase of murine microRNA-155 (miR-155), that was especially pronounced in non-parenchymal cells including liver-resident macrophages (Kupffer cells). Remarkably, ectopic upregulation of this miRNA in the liver of mice using robust hepatotropic adeno-associated virus 8 (AAV8) vectors enhanced GAP's protective capacity substantially. In turn, this AAV8-mediated miR-155 expression permitted a reduction of GAP injections needed to achieve complete protection against infectious parasite challenge from previously three to only one. Our study highlights a crucial role of mammalian miRNAs in Plasmodium liver infection in vivo and concurrently implies their great potential as future immune-augmenting agents in improved vaccination regimes against malaria and other diseases. PMID:25189739

  1. Enhancement of Gastric Ulcer Healing and Angiogenesis by Hepatocyte Growth Factor Gene Mediated by Attenuated Salmonella in Rats

    PubMed Central

    2017-01-01

    The present study developed an oral hepatocyte growth factor (HGF) gene therapy strategy for gastric ulcers treatment. An attenuated Salmonella typhimurium that stably expressed high HGF (named as TPH) was constructed, and the antiulcerogenic effect of TPH was evaluated in a rat model of gastric ulcers that created by acetic acid subserosal injection. From day 5 after injection, TPH (1 × 109 cfu), vehicle (TP, 1 × 109 cfu), or sodium bicarbonate (model control) was administered orally every alternate day for three times. Then ulcer size was measured at day 21 after ulcer induction. The ulcer area in TPH-treated group was 10.56 ± 3.30 mm2, which was smaller when compared with those in the TP-treated and model control groups (43.47 ± 4.18 and 56.25 ± 6.38 mm2, respectively). A higher level of reepithelialization was found in TPH-treated group and the crawling length of gastric epithelial cells was significantly longer than in the other two groups (P < 0.05). The microvessel density in the ulcer granulation tissues of the TPH-treated rats was 39.9 vessels/mm2, which was greater than in the TP-treated and model control rats, with a significant statistical difference. These results suggest that TPH treatment significantly accelerates the healing of gastric ulcers via stimulating proliferation of gastric epithelial cells and enhancing angiogenesis on gastric ulcer site. PMID:28049228

  2. Attenuating GABA(A) receptor signaling in dopamine neurons selectively enhances reward learning and alters risk preference in mice.

    PubMed

    Parker, Jones G; Wanat, Matthew J; Soden, Marta E; Ahmad, Kinza; Zweifel, Larry S; Bamford, Nigel S; Palmiter, Richard D

    2011-11-23

    Phasic dopamine (DA) transmission encodes the value of reward-predictive stimuli and influences both learning and decision-making. Altered DA signaling is associated with psychiatric conditions characterized by risky choices such as pathological gambling. These observations highlight the importance of understanding how DA neuron activity is modulated. While excitatory drive onto DA neurons is critical for generating phasic DA responses, emerging evidence suggests that inhibitory signaling also modulates these responses. To address the functional importance of inhibitory signaling in DA neurons, we generated mice lacking the β3 subunit of the GABA(A) receptor specifically in DA neurons (β3-KO mice) and examined their behavior in tasks that assessed appetitive learning, aversive learning, and risk preference. DA neurons in midbrain slices from β3-KO mice exhibited attenuated GABA-evoked IPSCs. Furthermore, electrical stimulation of excitatory afferents to DA neurons elicited more DA release in the nucleus accumbens of β3-KO mice as measured by fast-scan cyclic voltammetry. β3-KO mice were more active than controls when given morphine, which correlated with potential compensatory upregulation of GABAergic tone onto DA neurons. β3-KO mice learned faster in two food-reinforced learning paradigms, but extinguished their learned behavior normally. Enhanced learning was specific for appetitive tasks, as aversive learning was unaffected in β3-KO mice. Finally, we found that β3-KO mice had enhanced risk preference in a probabilistic selection task that required mice to choose between a small certain reward and a larger uncertain reward. Collectively, these findings identify a selective role for GABA(A) signaling in DA neurons in appetitive learning and decision-making.

  3. CCAAT-Enhancer-Binding Protein Homologous Protein Deficiency Attenuates Oxidative Stress and Renal Ischemia-Reperfusion Injury.

    PubMed

    Chen, Bo Lin; Sheu, Meei Ling; Tsai, Keh Sung; Lan, Kuo Cheng; Guan, Siao Syun; Wu, Cheng Tien; Chen, Li Ping; Hung, Kuan Yu; Huang, Jenq Wen; Chiang, Chih Kang; Liu, Shing Hwa

    2015-11-20

    Renal ischemia-reperfusion (I/R) is a major cause of acute renal failure. The mechanisms of I/R injury include endoplasmic reticulum (ER) stress, inflammatory responses, hypoxia, and generation of reactive oxygen species (ROS). CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) is involved in the ER stress signaling pathways. CHOP is a transcription factor and a major mediator of ER stress-induced apoptosis. However, the role of CHOP in renal I/R injury is still undefined. Here, we investigated whether CHOP could regulate I/R-induced renal injury using CHOP-knockout mice and cultured renal tubular cells as models. In CHOP-knockout mice, loss of renal function induced by I/R was prevented. Renal proximal tubule damage was induced by I/R in wild-type mice; however, the degree of alteration was significantly less in CHOP-knockout mice. CHOP deficiency also decreased the I/R-induced activation of caspase-3 and -8, apoptosis, and lipid peroxidation, whereas the activity of endogenous antioxidants increased. In an in vitro I/R model, small interfering RNA targeting CHOP significantly reversed increases in H2O2 formation, inflammatory signals, and apoptotic signals, while enhancing the activity of endogenous antioxidants in renal tubular cells. To the best of our knowledge, this is the first study which demonstrates that CHOP deficiency attenuates oxidative stress and I/R-induced acute renal injury both in vitro and in vivo. These findings suggest that CHOP regulates not only apoptosis-related signaling but also ROS formation and inflammation in renal tubular cells during I/R. CHOP may play an important role in the pathophysiology of I/R-induced renal injury.

  4. The Feverfew plant-derived compound, parthenolide enhances platelet production and attenuates platelet activation through NF-κB inhibition.

    PubMed

    Sahler, Julie; Bernard, Jamie J; Spinelli, Sherry L; Blumberg, Neil; Phipps, Richard P

    2011-05-01

    Few treatments are available that can safely and effectively stimulate new platelet production for thrombocytopenic patients. Additionally, recipients of transfused platelets may experience an inflammatory response due to stored platelets becoming unnecessarily activated, thus creating the need for suitable agents that will dampen undesirable platelet activation. We investigated the effect of the feverfew plant-derived compound, parthenolide on platelet production and platelet activation because of its well-studied ability to induce apoptosis or differentiation in some types of cancer. Parthenolide was used to treat human megakaryoblastic cell lines, primary human and mouse megakaryocytes. Resulting platelet production and function was measured via flow cytometry. The two most common parthenolide signaling mechanisms, oxidative stress and nuclear factor-κB inhibition, were assessed within the megakaryocytes using reactive oxygen species, glutathione and luciferase reporter assays. The influence of parthenolide on ex vivo platelet activation was tested with parthenolide pretreatment followed by collagen or thrombin activation. The resulting P-selectin surface expression and released soluble CD40 ligand was measured. Parthenolide stimulates functional platelet production from human megakaryocyte cell lines, and from primary mouse and human megakaryocytes in vitro. Parthenolide enhances platelet production via inhibition of nuclear factor-κB signaling in megakaryocytes and is independent of the parthenolide-induced oxidative stress response. Additionally, parthenolide treatment of human peripheral blood platelets attenuated activation of stimulated platelets. Overall, these data reveal that parthenolide has strong potential as a candidate to enhance platelet production and to dampen undesirable platelet activation. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Ideals and Category Typicality

    ERIC Educational Resources Information Center

    Kim, ShinWoo; Murphy, Gregory L.

    2011-01-01

    Barsalou (1985) argued that exemplars that serve category goals become more typical category members. Although this claim has received support, we investigated (a) whether categories have a single ideal, as negatively valenced categories (e.g., cigarette) often have conflicting goals, and (b) whether ideal items are in fact typical, as they often…

  6. Ideals and Category Typicality

    ERIC Educational Resources Information Center

    Kim, ShinWoo; Murphy, Gregory L.

    2011-01-01

    Barsalou (1985) argued that exemplars that serve category goals become more typical category members. Although this claim has received support, we investigated (a) whether categories have a single ideal, as negatively valenced categories (e.g., cigarette) often have conflicting goals, and (b) whether ideal items are in fact typical, as they often…

  7. Rank 4 Premodular Categories

    SciTech Connect

    Bruillard, Paul J.; Galindo, Cesar; Ng, Siu Hung; Plavnik, Julia; Rowell, Eric; Wang, Zhenghan

    2016-09-01

    We consider the classification problem for rank 4 premodular categories. We uncover a formula for the 2nd Frobenius-Schur indicator of a premodular category is determined and the classification of rank 4 premodular categories (up to Grothendieck equivalence) is completed. In the appendix we show rank finiteness for premodular categories.

  8. Humic Acids Enhanced U(VI) Attenuation in Acidic Waste Plumes: An In-situ Remediation Approach

    NASA Astrophysics Data System (ADS)

    Wan, J.; Dong, W.; Tokunaga, T. K.

    2010-12-01

    and HA by groundwater leaching are non-detectable over a long period of time (200 days and > 100 PV without further addition of HA). As a natural reactive agent for in-situ remediation, HAs are cost-effective (enormous reservoir in nature), nontoxic, resistant to biodegradation, soluble, and easily introducible to the subsurface. This method has high potential to efficiently and sustainably enhance natural attenuation of U within acidic waste plumes.

  9. Effects of contrast medium injection technique on attenuation values of adrenal glands in healthy dogs during contrast-enhanced computed tomography.

    PubMed

    Blaser, Alexandra; Dennler, Matthias; Mosing, Martina; Gent, Thomas C; Santner, Guido; Imhasly, Sandro; Boretti, Felicitas S; Reusch, Claudia E; Kircher, Patrick; Sieber-Ruckstuhl, Nadja S

    2016-02-01

    To assess the effects of 3 contrast medium injection techniques on attenuation values for canine adrenal glands during contrast-enhanced CT. 9 healthy Beagles. 3 protocols were evaluated in a randomized cross-over design study: 700 mg of iodine/kg at a constant injection rate over 20 seconds (full-dose constant rate), the same dose at a rate following an exponential decay curve over 20 seconds (full-dose decelerated rate), and 350 mg of iodine/kg at a constant injection rate over 10 seconds (half-dose constant rate). Multislice CT images were obtained before and at predetermined time points after the start of contrast medium injection. Median peak attenuation values were 129, 133, and 87 Hounsfield units with the full-dose constant rate, full-dose decelerated rate, and half-dose constant rate injection protocols, respectively. Peak attenuation differed significantly between the full-dose constant rate and half-dose constant rate injection protocols and between the full-dose decelerated rate and half-dose constant rate injection protocols. Median time to peak attenuation did not differ significantly among injection methods and was 30, 23, and 15 seconds for the full-dose constant rate, full-dose decelerated rate, and half-dose constant rate injections, respectively. The dose of contrast medium and the timing of postinjection CT scanning were main determinants of peak attenuation for adrenal glands in healthy dogs; effects of the 3 injection protocols on attenuation were minor. The exponentially decelerated injection method was subjectively complex. A constant injection protocol delivering 700 mg of iodine/kg over 20 seconds, with scans obtained approximately 30 seconds after starting contrast medium injection, provided images with maximum adrenal gland attenuation values.

  10. Enhanced Attenuation: Chlorinated Organics

    DTIC Science & Technology

    2008-04-01

    cement, bentonite , clay -based materials (alone or in combination with reactive materials such as zero-valent iron), and edible oils. While most of the...groundwater flowing through the source. Barrier types span the range from slurry walls (cement/ bentonite ) and sheet piling to impermeable membranes and...sand with interbedded clays deposited in shallow marine, lagoonal, or fluvial environments. As the rate of solvent removal diminished, engineers

  11. High-fat Diet Enhances and Plasminogen Activator Inhibitor-1 Deficiency Attenuates Bone Loss in Mice with Lewis Lung Carcinoma.

    PubMed

    Yan, Lin; Nielsen, Forrest H; Sundaram, Sneha; Cao, Jay

    2015-07-01

    This study determined the effects of a high-fat diet and plasminogen activator inhibitor-1 deficiency (Pai1(-/-)) on the bone structure in male C57BL/6 mice bearing Lewis lung carcinoma (LLC) in lungs. Significant reduction in bone volume fraction (BV/TV), trabecular number (Tb.N) and bone mineral density (BMD) in femurs and vertebrae were found in LLC-bearing mice compared to non-tumor-bearing mice. In LLC-bearing mice, the high-fat diet compared to the AIN93G control diet significantly reduced BV/TV, Tb.N and BMD in femurs and BV/TV in vertebrae. The high-fat diet significantly reduced BMD in vertebrae in wild-type mice but not in Pai1(-/-) mice. Compared to wild-type mice, PAI1 deficiency significantly increased BV/TV and Tb.N in femurs. The plasma concentration of osteocalcin was significantly lower and that of tartrate-resistant acid phosphatase 5b (TRAP5b) was significantly higher in LLC-bearing mice. The high-fat diet significantly reduced plasma osteocalcin and increased TRAP5b. Deficiency in PAI1 prevented the high-fat diet-induced increases in plasma TRAP5b. These findings demonstrate that a high-fat diet enhances, whereas PAI1 deficiency, attenuates metastasis-associated bone loss, indicating that a high-fat diet and PAI1 contribute to metastasis-associated bone deterioration. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention.

    PubMed

    Danoviz, Maria E; Nakamuta, Juliana S; Marques, Fabio L N; dos Santos, Leonardo; Alvarenga, Erica C; dos Santos, Alexandra A; Antonio, Ednei L; Schettert, Isolmar T; Tucci, Paulo J; Krieger, Jose E

    2010-08-10

    Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). 99mTc-labeled ASCs (1x10(6) cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administering co-injection of ASCs with biopolymers.

  13. Rat Adipose Tissue-Derived Stem Cells Transplantation Attenuates Cardiac Dysfunction Post Infarction and Biopolymers Enhance Cell Retention

    PubMed Central

    Danoviz, Maria E.; Nakamuta, Juliana S.; Marques, Fabio L. N.; dos Santos, Leonardo; Alvarenga, Erica C.; dos Santos, Alexandra A.; Antonio, Ednei L.; Schettert, Isolmar T.; Tucci, Paulo J.; Krieger, Jose E.

    2010-01-01

    Background Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). Methodology/Principal Findings 99mTc-labeled ASCs (1×106 cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by γ-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8±2.0 and 26.8±2.4% vs. 4.8±0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. Conclusions We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administrating co-injection of ASCs with biopolymers. PMID:20711471

  14. Enhanced platelet reactivity and thrombosis in Apoe-/- mice exposed to cigarette smoke is attenuated by P2Y12 antagonism.

    PubMed

    Dong, Anping; Caicedo, Jessica; Han, Sung Gu; Mueller, Paul; Saha, Sibu; Smyth, Susan S; Gairola, C Gary

    2010-10-01

    Smoking increases the risk of acute arterial thrombosis, including myocardial infarction, likely due to multi-factorial effects on the vasculature. Heightened platelet reactivity may be among the adverse effects of smoke exposure. To examine the effects of smoke exposure on platelet function in an atherosclerotic environment, Apoe-deficient female mice, maintained on a Western diet, were exposed (4 hrs/d, 5 d/wk) to sidestream cigarette smoke in a whole-body exposure chamber for 12 weeks. A separate group of wild type C57BL/6J mice were also exposed to smoke in an identical fashion. In comparison to control Apoe-/- mice exposed to filtered ambient air, smoke-exposed Apoe-/- mice displayed a 1.8±0.3 fold enhanced ADP-induced fibrinogen binding ex vivo (P<0.001) and had a shorter time to thrombotic occlusion following ferric chloride injury of the carotid artery (median time to thrombosis of 8 vs. 13 min; P=0.015). Administration of the direct-acting P2Y12 antagonist cangrelor blunted ex vivo fibrinogen binding and attenuated thrombosis (median time 20 min) in Apoe-/- mice exposed to sidestream smoke. The effects of smoke exposure required a proatherosclerotic background, as wild-type C57Bl/6J mice exposed to smoke displayed similar fibrinogen binding and thrombotic occlusion times as did control mice. Our results demonstrate that exposure to smoke heightens platelet reactivity and thrombosis in Apoe-/- mice and implicate signaling through platelet P2Y12 receptor as a mediator of the adverse consequence of smoke exposure. These results may partially explain the recent observations that smokers derive greater clinical benefit from the P2Y12 antagonist clopidogrel than do non-smokers. Published by Elsevier Ltd.

  15. Helenalin attenuates alcohol-induced hepatic fibrosis by enhancing ethanol metabolism, inhibiting oxidative stress and suppressing HSC activation.

    PubMed

    Lin, Xing; Zhang, Shijun; Huang, Renbin; Wei, Ling; Tan, Shimei; Liang, Shuang; Tian, Yuanchun; Wu, Xiaoyan; Lu, Zhongpeng; Huang, Quanfang

    2014-06-01

    A compound was isolated from Centipeda minima using bioassay-guided screening. The structure of this compound was elucidated based on its spectral data, and it was identified as helenalin. The hepatoprotective effect of helenalin was evaluated using a liver fibrosis model induced by intragastric administration with alcohol within 24 weeks in rats. The results revealed that helenalin significantly prevented alcohol-induced hepatic injury and fibrogenesis, as evidenced by the decrease in serum aminotransferase, the attenuation of histopathological changes, and the inhibition of the hepatic fibrosis indicators, such as hyaluronic acid, type III precollagen, laminin, hydroxyproline and collagen α type I. Mechanistically, studies showed that helenalin expedited ethanol metabolism by enhancing the alcohol and aldehyde dehydrogenase activities. Furthermore, helenalin alleviated lipid peroxidation, recruited the antioxidative defense system, inhibited CYP2E1 activity, and reduced the inflammatory mediators, including TGF-β1, TNF-α, IL-6 and IL-1β and myeloperoxidase, via down-regulation of NF-κB. Helenalin significantly decreased collagen deposition by reducing the profibrotic cytokines like transforming growth factor-β, platelet-derived growth factor-β and connective tissue growth factor, and promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9. In addition, helenalin inhibited HSC activation as evidenced by the down-regulation of α-SMA and TGF-β levels. In conclusion, helenalin had a significant protective effect on chronic ethanol-induced hepatic fibrosis and may be a major bioactive ingredient of C. minima.

  16. Pglyrp-Regulated Gut Microflora Prevotella falsenii, Parabacteroides distasonis and Bacteroides eggerthii Enhance and Alistipes finegoldii Attenuates Colitis in Mice

    PubMed Central

    Dziarski, Roman; Dowd, Scot E.; Gupta, Dipika

    2016-01-01

    Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it is unclear which specific intestinal bacteria predispose to and which protect from IBD and how they are regulated. Peptidoglycan recognition proteins (Pglyrps) are antibacterial, participate in maintaining intestinal microflora, and modulate inflammatory responses. Mice deficient in any one of the four Pglyrp genes are more sensitive to dextran sulfate sodium (DSS)-induced colitis, and stools from Pglyrp-deficient mice transferred to wild type (WT) germ-free mice predispose them to much more severe colitis than stools from WT mice. However, the identities of these Pglyrp-regulated bacteria that predispose Pglyrp-deficient mice to colitis or protect WT mice from colitis are not known. Here we identified significant changes in β-diversity of stool bacteria in Pglyrp-deficient mice compared with WT mice. The most consistent changes in microbiome in all Pglyrp-deficient mice were in Bacteroidales, from which we selected four species, two with increased abundance (Prevotella falsenii and Parabacteroides distasonis) and two with decreased abundance (Bacteroides eggerthii and Alistipes finegoldii). We then gavaged WT mice with stock type strains of these species to test the hypothesis that they predispose to or protect from DSS-induced colitis. P. falsenii, P. distasonis, and B. eggerthii all enhanced DSS-induced colitis in both WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora. By contrast, A. finegoldii (which is the most abundant species in WT mice) attenuated DSS-induced colitis both in WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora, similar to the colitis protective effect of the entire normal microflora. These results identify P. falsenii, P. distasonis, and B. eggerthii as colitis-promoting species and A. finegoldii as colitis-protective species. PMID

  17. Pglyrp-Regulated Gut Microflora Prevotella falsenii, Parabacteroides distasonis and Bacteroides eggerthii Enhance and Alistipes finegoldii Attenuates Colitis in Mice.

    PubMed

    Dziarski, Roman; Park, Shin Yong; Kashyap, Des Raj; Dowd, Scot E; Gupta, Dipika

    2016-01-01

    Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it is unclear which specific intestinal bacteria predispose to and which protect from IBD and how they are regulated. Peptidoglycan recognition proteins (Pglyrps) are antibacterial, participate in maintaining intestinal microflora, and modulate inflammatory responses. Mice deficient in any one of the four Pglyrp genes are more sensitive to dextran sulfate sodium (DSS)-induced colitis, and stools from Pglyrp-deficient mice transferred to wild type (WT) germ-free mice predispose them to much more severe colitis than stools from WT mice. However, the identities of these Pglyrp-regulated bacteria that predispose Pglyrp-deficient mice to colitis or protect WT mice from colitis are not known. Here we identified significant changes in β-diversity of stool bacteria in Pglyrp-deficient mice compared with WT mice. The most consistent changes in microbiome in all Pglyrp-deficient mice were in Bacteroidales, from which we selected four species, two with increased abundance (Prevotella falsenii and Parabacteroides distasonis) and two with decreased abundance (Bacteroides eggerthii and Alistipes finegoldii). We then gavaged WT mice with stock type strains of these species to test the hypothesis that they predispose to or protect from DSS-induced colitis. P. falsenii, P. distasonis, and B. eggerthii all enhanced DSS-induced colitis in both WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora. By contrast, A. finegoldii (which is the most abundant species in WT mice) attenuated DSS-induced colitis both in WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora, similar to the colitis protective effect of the entire normal microflora. These results identify P. falsenii, P. distasonis, and B. eggerthii as colitis-promoting species and A. finegoldii as colitis-protective species.

  18. Evaluation of synthetic infection-enhancing lipopeptides as adjuvants for a live-attenuated canine distemper virus vaccine administered intra-nasally to ferrets.

    PubMed

    Nguyen, D Tien; Ludlow, Martin; van Amerongen, Geert; de Vries, Rory D; Yüksel, Selma; Verburgh, R Joyce; Osterhaus, Albert D M E; Duprex, W Paul; de Swart, Rik L

    2012-07-20

    Inactivated paramyxovirus vaccines have been associated with hypersensitivity responses upon challenge infection. For measles and canine distemper virus (CDV) safe and effective live-attenuated virus vaccines are available, but for human respiratory syncytial virus and human metapneumovirus development of such vaccines has proven difficult. We recently identified three synthetic bacterial lipopeptides that enhance paramyxovirus infections in vitro, and hypothesized these could be used as adjuvants to promote immune responses induced by live-attenuated paramyxovirus vaccines. Here, we tested this hypothesis using a CDV vaccination and challenge model in ferrets. Three groups of six animals were intra-nasally vaccinated with recombinant (r) CDV(5804P)L(CCEGFPC) in the presence or absence of the infection-enhancing lipopeptides Pam3CSK4 or PHCSK4. The recombinant CDV vaccine virus had previously been described to be over-attenuated in ferrets. A group of six animals was mock-vaccinated as control. Six weeks after vaccination all animals were challenged with a lethal dose of rCDV strain Snyder-Hill expressing the red fluorescent protein dTomato. Unexpectedly, intra-nasal vaccination of ferrets with rCDV(5804P)L(CCEGFPC) in the absence of lipopeptides resulted in good immune responses and protection against lethal challenge infection. However, in animals vaccinated with lipopeptide-adjuvanted virus significantly higher vaccine virus loads were detected in nasopharyngeal lavages and peripheral blood mononuclear cells. In addition, these animals developed significantly higher CDV neutralizing antibody titers compared to animals vaccinated with non-adjuvanted vaccine. This study demonstrates that the synthetic cationic lipopeptides Pam3CSK4 and PHCSK4 not only enhance paramyxovirus infection in vitro, but also in vivo. Given the observed enhancement of immunogenicity their potential as adjuvants for other live-attenuated paramyxovirus vaccines should be considered

  19. Categories of Arrhythmias

    MedlinePlus

    ... previous page En español Aneurysms and Dissections Angina Arrhythmia Bundle Branch Block Cardiomyopathy Carotid Artery Disease Chronic ... Cardiac Arrest Valve Disease Vulnerable Plaque Categories of Arrhythmias Arrhythmias are generally divided into two categories: ventricular ...

  20. cAMP attenuates the enhanced expression of Gi proteins and hyperproliferation of vascular smooth muscle cells from SHR: role of ROS and ROS-mediated signaling.

    PubMed

    Gusan, Svetlana; Anand-Srivastava, Madhu B

    2013-06-15

    We previously showed that angiotensin II (ANG II)-induced overexpression of inhibitory G proteins (Gi) was attenuated by dibutyryl-cAMP (db-cAMP) in A10 vascular smooth muscle cells (VSMC). Since enhanced levels of endogenous ANG II contributed to the overexpression of Gi protein and hyperproliferation of VSMC from spontaneously hypertensive rats (SHR), the present study was therefore undertaken to examine if cAMP could also attenuate the overexpression of Gi proteins and hyperproliferation of VSMC from SHR and to explore the underlying molecular mechanisms responsible for this response. The enhanced expression of Giα proteins in VSMC from SHR and Nω-nitro-L-arginine methyl ester hypertensive rats was decreased by db-cAMP. In addition, enhanced inhibition of adenylyl cyclase by inhibitory hormones and forskolin-stimulated adenylyl cyclase activity by low concentration of GTPγS in VSMC from SHR was also restored to Wistar-Kyoto (WKY) levels by db-cAMP. Furthermore, db-cAMP also attenuated the hyperproliferation and the increased production of superoxide anion, NAD(P)H oxidase activity, overexpression of Nox1/Nox2/Nox4 and p47phox proteins, increased phosphorylation of PDGF-receptor (R), EGF-R, c-Src, and ERK1/2 to control levels. In addition, the protein kinase A (PKA) inhibitor reversed the effects of db-cAMP on the expression of Nox4 and Giα proteins and hyperproliferation of VSMC from SHR to WKY levels, while stimulation of the exchange protein directly activated by cAMP did not have any effect on these parameters. These results suggest that cAMP via PKA pathway attenuates the overexpression of Gi proteins and hyperproliferation of VSMC from SHR through the inhibition of ROS and ROS-mediated transactivation of EGF-R/PDGF-R and MAPK signaling pathways.

  1. Saikokeishito Extract Exerts a Therapeutic Effect on α-Naphthylisothiocyanate-Induced Liver Injury in Rats through Attenuation of Enhanced Neutrophil Infiltration and Oxidative Stress in the Liver Tissue

    PubMed Central

    Ohta, Yoshiji; Kongo-Nishimura, Mutsumi; Hayashi, Takahiro; Kitagawa, Akira; Matsura, Tatsuya; Yamada, Kazuo

    2007-01-01

    We examined whether Saikokeishito extract (TJ-10), a traditional Japanese herbal medicine, exerts a therapeutic effect on α-naphthylisothiocyanate (ANIT)-induced liver injury in rats through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue. In rats treated once with ANIT (75 mg/kg, i.p.), liver injury with cholestasis occurred 24 h after treatment and progressed at 48 h. When ANIT-treated rats orally received TJ-10 (0.26, 1.3 or 2.6 g/kg) at 24 h after the treatment, progressive liver injury with cholestasis was significantly attenuated at 48 h after the treatment at the dose of 1.3 or 2.6 g/kg. At 24 h after ANIT treatment, increases in hepatic lipid peroxide and reduced glutathione contents and myeloperoxidase activity occurred with decreases in hepatic superoxide dismutase and glutathione reductase activities. At 48 h after ANIT treatment, these changes except for reduced glutathione were enhanced with decreases in catalase, Se-glutathione peroxidase, and glucose-6-phosphate dehydrogenase activities. TJ-10 (1.3 or 2.6 g/kg) post-administered to ANIT-treated rats attenuated these changes found at 48 h after the treatment significantly. These results indicate that TJ-10 exerts a therapeutic effect on ANIT-induced liver injury in rats possibly through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue. PMID:18437211

  2. Encoding tasks dissociate the effects of divided attention on category-cued recall and category-exemplar generation.

    PubMed

    Parker, Andrew; Dagnall, Neil; Munley, Gary

    2012-01-01

    The combined effects of encoding tasks and divided attention upon category-exemplar generation and category-cued recall were examined. Participants were presented with pairs of words each comprising a category name and potential example of that category. They were then asked to indicate either (i) their liking for both of the words or (ii) if the exemplar was a member of the category. It was found that divided attention reduced performance on the category-cued recall task under both encoding conditions. However, performance on the category-exemplar generation task remained invariant across the attention manipulation following the category judgment task. This provides further evidence that the processes underlying performance on conceptual explicit and implicit memory tasks can be dissociated, and that the intentional formation of category-exemplar associations attenuates the effects of divided attention on category-exemplar generation.

  3. Deletion of Major Nonessential Genomic Regions in the Vaccinia Virus Lister Strain Enhances Attenuation without Altering Vaccine Efficacy in Mice▿

    PubMed Central

    Dimier, Julie; Ferrier-Rembert, Audrey; Pradeau-Aubreton, Karine; Hebben, Matthias; Spehner, Danièle; Favier, Anne-Laure; Gratier, Danielle; Garin, Daniel; Crance, Jean-Marc; Drillien, Robert

    2011-01-01

    The vaccinia virus (VACV) Lister strain was one of the vaccine strains that enabled smallpox eradication. Although the strain is most often harmless, there have been numerous incidents of mild to life-threatening accidents with this strain and others. In an attempt to further attenuate the Lister strain, we investigated the role of 5 genomic regions known to be deleted in the modified VACV Ankara (MVA) genome in virulence in immunodeficient mice, immunogenicity in immunocompetent mice, and vaccine efficacy in a cowpox virus challenge model. Lister mutants were constructed so as to delete each of the 5 regions or various combinations of these regions. All of the mutants replicated efficiently in tissue culture except region I mutants, which multiplied more poorly in human cells than the parental strain. Mutants with single deletions were not attenuated or only moderately so in athymic nude mice. Mutants with multiple deletions were more highly attenuated than those with single deletions. Deleting regions II, III, and V together resulted in total attenuation for nude mice and partial attenuation for SCID mice. In immunocompetent mice, the Lister deletion mutants induced VACV specific humoral responses equivalent to those of the parental strain but in some cases lower cell-mediated immune responses. All of the highly attenuated mutants protected mice from a severe cowpox virus challenge at low vaccine doses. The data suggest that several of the Lister mutants combining multiple deletions could be used in smallpox vaccination or as live virus vectors at doses equivalent to those used for the traditional vaccine while displaying increased safety. PMID:21367889

  4. Incidental Auditory Category Learning

    PubMed Central

    Gabay, Yafit; Dick, Frederic K.; Zevin, Jason D.; Holt, Lori L.

    2015-01-01

    Very little is known about how auditory categories are learned incidentally, without instructions to search for category-diagnostic dimensions, overt category decisions, or experimenter-provided feedback. This is an important gap because learning in the natural environment does not arise from explicit feedback and there is evidence that the learning systems engaged by traditional tasks are distinct from those recruited by incidental category learning. We examined incidental auditory category learning with a novel paradigm, the Systematic Multimodal Associations Reaction Time (SMART) task, in which participants rapidly detect and report the appearance of a visual target in one of four possible screen locations. Although the overt task is rapid visual detection, a brief sequence of sounds precedes each visual target. These sounds are drawn from one of four distinct sound categories that predict the location of the upcoming visual target. These many-to-one auditory-to-visuomotor correspondences support incidental auditory category learning. Participants incidentally learn categories of complex acoustic exemplars and generalize this learning to novel exemplars and tasks. Further, learning is facilitated when category exemplar variability is more tightly coupled to the visuomotor associations than when the same stimulus variability is experienced across trials. We relate these findings to phonetic category learning. PMID:26010588

  5. Electroacupuncture attenuates visceral hyperalgesia and inhibits the enhanced excitability of colon specific sensory neurons in a rat model of irritable bowel syndrome.

    PubMed

    Xu, G-Y; Winston, J H; Chen, J D Z

    2009-12-01

    The causes of irritable bowel syndrome remain elusive and there are few effective treatments for pain in this syndrome. Electroacupunture (EA) is used extensively for treatment of various painful conditions including chronic visceral hyperalgesia (CVH). However, mechanism of its analgesic effect remains unknown. This study was designed to investigate effect of EA on colon specific dorsal root ganglion (DRG) neurons in rats with CVH. CVH was induced by intracolonic injection of acetic acid (AA) in 10-day-old rats. Electromyography and patch clamp recordings were performed at age of 8-10 weeks. Colon DRG neurons were labelled by injection of DiI into the colon wall. EA was given at ST36 in both hindlimbs. As adults, neonatal AA-injected rats displayed an increased sensitivity to colorectal distension (CRD) and an enhanced excitability of colon DRG neurons. EA treatment for 40 min significantly attenuated the nociceptive responses to CRD in these rats; this attenuation was reversed by pretreatment with naloxone. EA treatment for 40 min per day for 5 days produced a prolonged analgesic effect and normalized the enhanced excitability of colon DRG neurons. Furthermore, in vitro application of [D-Ala(2), N-MePhe(4), Gly(5)-Ol] enkephalin (DAMGO) suppressed the enhanced excitability of colon neurons from rats with CVH. These findings suggest that EA produced-visceral analgesia, which might be mediated in a large part by endogenous opioids pathways, is associated with reversal of the enhanced excitability of colon DRG neurons in rats with CVH.

  6. Valuation, Categories and Attributes

    PubMed Central

    Galperin, Inna; Sorenson, Olav

    2014-01-01

    Existing research on categories has only examined indirectly the value associated with being a member of a category relative to the value of the set of attributes that determine membership in that category. This study uses survey data to analyze consumers' preferences for the "organic” label versus for the attributes underlying that label. We found that consumers generally preferred products with the category label to those with the attributes required for the organic label but without the label. We also found that the value accorded to the organic label increased with the number of attributes that an individual associated with the category. Category membership nevertheless still had greater value than even that of the sum of the attributes associated with it. PMID:25111831

  7. Cerebrospinal Fluid Enhancement on Fluid Attenuated Inversion Recovery Images After Carotid Artery Stenting with Neuroprotective Balloon Occlusions: Hemodynamic Instability and Blood-Brain Barrier Disruption

    SciTech Connect

    Ogami, Ryo Nakahara, Toshinori; Hamasaki, Osamu; Araki, Hayato; Kurisu, Kaoru

    2011-10-15

    Purpose: A rare complication of carotid artery stenting (CAS), prolonged reversible neurological symptoms with delayed cerebrospinal fluid (CSF) space enhancement on fluid attenuated inversion recovery (FLAIR) images, is associated with blood-brain barrier (BBB) disruption. We prospectively identified patients who showed CSF space enhancement on FLAIR images. Methods: Nineteen patients-5 acute-phase and 14 scheduled-underwent 21 CAS procedures. Balloon catheters were navigated across stenoses, angioplasty was performed using a neuroprotective balloon, and stents were placed with after dilation under distal balloon protection. CSF space hyperintensity or obscuration on FLAIR after versus before CAS indicated CSF space enhancement. Correlations with clinical factors were examined. Results: CSF space was enhanced on FLAIR in 12 (57.1%) cases. Postprocedural CSF space enhancement was significantly related to age, stenosis rate, acute-stage procedure, and total occlusion time. All acute-stage CAS patients showed delayed enhancement. Only age was associated with delayed CSF space enhancement in scheduled CAS patients. Conclusions: Ischemic intolerance for severe carotid artery stenosis and temporary neuroprotective balloon occlusion, causing reperfusion injury, seem to be the main factors that underlie BBB disruption with delayed CSF space enhancement shortly after CAS, rather than sudden poststenting hemodynamic change. Our results suggest that factors related to hemodynamic instability or ischemic intolerance seem to be associated with post-CAS BBB vulnerability. Patients at risk for hemodynamic instability or with ischemic intolerance, which decrease BBB integrity, require careful management to prevent intracranial hemorrhagic and other post-CAS complications.

  8. Single well field injection test of humate to enhance attenuation of uranium and other radionuclides in an acidic plume

    SciTech Connect

    Denham, M.

    2014-09-30

    This report documents the impact of the injected humate on targeted contaminants over a period of 4 months and suggests it is a viable attenuation-based remedy for uranium, potentially for I-129, but not for Sr-90. Future activities will focus on issues pertinent to scaling the technology to full deployment.

  9. BLOCKADE OF NERVE GROWTH FACTOR (NGF) RECEPTOR TRKA ATTENUATES DIESEL EXHAUST PARTICULATE MATTER (DEP) ENHANCEMENT OF ALLERGIC INFLAMMATION

    EPA Science Inventory


    Recent studies have shown that asthmatics have increased levels of the neurotrophin, NGF, in their lungs. In addition, antibody blockade of NGF in mice attenuates airway resistance associated with allergic airway responses. DEP has been linked to asthma exacerbation in many c...

  10. BLOCKADE OF NERVE GROWTH FACTOR (NGF) RECEPTOR TRKA ATTENUATES DIESEL EXHAUST PARTICULATE MATTER (DEP) ENHANCEMENT OF ALLERGIC INFLAMMATION

    EPA Science Inventory


    Recent studies have shown that asthmatics have increased levels of the neurotrophin, NGF, in their lungs. In addition, antibody blockade of NGF in mice attenuates airway resistance associated with allergic airway responses. DEP has been linked to asthma exacerbation in many c...

  11. Asian women have attenuated sympathetic activation but enhanced renal–adrenal responses during pregnancy compared to Caucasian women

    PubMed Central

    Okada, Yoshiyuki; Best, Stuart A; Jarvis, Sara S; Shibata, Shigeki; Parker, Rosemary S; Casey, Brian M; Levine, Benjamin D; Fu, Qi

    2015-01-01

    women. This is the first longitudinal study to investigate neural and humoral responses during pregnancy in Asians and Caucasians. The key finding was that Asians had attenuated sympathetic activation but enhanced renal–adrenal responsiveness during pregnancy compared to Caucasians. These results may provide insights into the pathophysiological mechanisms for racial differences in the prevalence of hypertensive disorders during pregnancy. PMID:25545472

  12. Categories and Music Transmission

    ERIC Educational Resources Information Center

    Gatien, Greg

    2009-01-01

    Lucy Green's (2008) "Music, Informal Learning, and the School: A New Classroom Pedagogy" gives rise to an interesting corollary. Does the manner of music's transmission inform one's understanding of a musical category? While categories of music can be difficult to define according to strict musical characteristics, a better understanding of…

  13. Rethinking the Category 'Determiner'

    ERIC Educational Resources Information Center

    Spangler, Wayne E.

    1975-01-01

    The 'determiner' category was originally set up by structuralists for identifying nouns. The rewrite rule for 'determiners' in transformational generative grammar is inadequate for showing correspondences between type and token. An appraisal of quantity terms might eliminate the concept of the 'determiner,' and replace that category with one of…

  14. Categories and Music Transmission

    ERIC Educational Resources Information Center

    Gatien, Greg

    2009-01-01

    Lucy Green's (2008) "Music, Informal Learning, and the School: A New Classroom Pedagogy" gives rise to an interesting corollary. Does the manner of music's transmission inform one's understanding of a musical category? While categories of music can be difficult to define according to strict musical characteristics, a better understanding of…

  15. Categories of Parent Involvement.

    ERIC Educational Resources Information Center

    Bauch, Jerold P.

    1994-01-01

    The growing interest in effective parent involvement has produced several ways to classify or describe ways parents are or should be involved. This article reviews and evaluates Ira Gordon's systems approach, the California-based System Development Corporation's categories, Eugenia H. Berger's parental role categories, Chavkin and Williams' parent…

  16. Social stress-enhanced severity of Citrobacter rodentium-induced colitis is CCL2-dependent and attenuated by probiotic Lactobacillus reuteri.

    PubMed

    Mackos, A R; Galley, J D; Eubank, T D; Easterling, R S; Parry, N M; Fox, J G; Lyte, M; Bailey, M T

    2016-03-01

    Psychological stressors are known to affect colonic diseases but the mechanisms by which this occurs, and whether probiotics can prevent stressor effects, are not understood. Because inflammatory monocytes that traffic into the colon can exacerbate colitis, we tested whether CCL2, a chemokine involved in monocyte recruitment, was necessary for stressor-induced exacerbation of infectious colitis. Mice were exposed to a social disruption stressor that entails repeated social defeat. During stressor exposure, mice were orally challenged with Citrobacter rodentium to induce a colonic inflammatory response. Exposure to the stressor during challenge resulted in significantly higher colonic pathogen levels, translocation to the spleen, increases in colonic macrophages, and increases in inflammatory cytokines and chemokines. The stressor-enhanced severity of C. rodentium-induced colitis was not evident in CCL2(-/-) mice, indicating the effects of the stressor are CCL2-dependent. In addition, we tested whether probiotic intervention could attenuate stressor-enhanced infectious colitis by reducing monocyte/macrophage accumulation. Treating mice with probiotic Lactobacillus reuteri reduced CCL2 mRNA levels in the colon and attenuated stressor-enhanced infectious colitis. These data demonstrate that probiotic L. reuteri can prevent the exacerbating effects of stressor exposure on pathogen-induced colitis, and suggest that one mechanism by which this occurs is through downregulation of the chemokine CCL2.

  17. Selected prfA* mutations in recombinant attenuated Listeria monocytogenes strains augment expression of foreign immunogens and enhance vaccine-elicited humoral and cellular immune responses.

    PubMed

    Yan, Lin; Qiu, Jin; Chen, Jianbo; Ryan-Payseur, Bridgett; Huang, Dan; Wang, Yunqi; Rong, Lijun; Melton-Witt, Jody A; Freitag, Nancy E; Chen, Zheng W

    2008-08-01

    While recombinant Listeria monocytogenes strains can be explored as vaccine candidates, it is important to develop attenuated but highly immunogenic L. monocytogenes vaccine vectors. Here, prfA* mutations selected on the basis of upregulated expression of L. monocytogenes PrfA-dependent genes and proteins were assessed to determine their abilities to augment expression of foreign immunogens in recombinant L. monocytogenes vectors and therefore enhance vaccine-elicited immune responses (a prfA* mutation is a mutation that results in constitutive overexpression of PrfA and PrfA-dependent virulence genes; the asterisk distinguishes the mutation from inactivation or stop mutations). A total of 63 recombinant L. monocytogenes vaccine vectors expressing seven individual viral or bacterial immunogens each in nine different L. monocytogenes strains carrying wild-type prfA or having prfA* mutations were constructed and investigated. Mutations selected on the basis of increased PrfA activation in recombinant L. monocytogenes prfA* vaccine vectors augmented expression of seven individual protein immunogens remarkably. Consistently, prime and boost vaccination studies with mice indicated that the prfA(G155S) mutation in recombinant L. monocytogenes DeltaactA prfA* strains enhanced vaccine-elicited cellular immune responses. Surprisingly, the prfA(G155S) mutation was found to enhance vaccine-elicited humoral immune responses as well. The highly immunogenic recombinant L. monocytogenes DeltaactA prfA* vaccine strains were as attenuated as the recombinant parent L. monocytogenes DeltaactA vaccine vector. Thus, recombinant attenuated L. monocytogenes DeltaactA prfA* vaccine vectors potentially are better antimicrobial and anticancer vaccines.

  18. Multiple vaccinations with UV- attenuated cercariae in pig enhance protective immunity against Schistosoma japonicum infection as compared to single vaccination.

    PubMed

    Lin, Dandan; Tian, Fang; Wu, Haiwei; Gao, Yanan; Wu, Jingjiao; Zhang, Donghui; Ji, Minjun; McManus, Donald P; Driguez, Patrick; Wu, Guanling

    2011-06-10

    Schistosomiasis japonica is a major public health problem in the endemic areas of China, the Philippines, and Indonesia. To date, a vaccine has not been developed against this disease but immunization with UV-attenuated cercariae can induce a high level of protective immunity in Landrace/Yorkshire/Duroc crossbred pigs. To compare the efficacy of a single vaccination and multiple vaccinations with UV-attenuated Schistosoma japonicum cercariae, two groups of pigs received either one or three exposures to 10,000 cercariae attenuated with 400 μw UV. Pigs with a single immunization had a 59.33% reduction in adult worm burden, a 89.87% reduction in hepatic eggs and a 86.27% reduction in fecal eggs at eight weeks post-challenge (P < 0.01). After three immunizations, protection increased to 77.62%, 88.8% and 99.78% reduction in adult worms, hepatic eggs and fecal eggs, respectively (P < 0.01). Humoral and cellular immunological parameters measured indicated that schistosome-specific IgG1 and IgG2 levels in the vaccinated groups were higher than in the infection-control group. Triple vaccinations resulted in higher levels of antibodies, especially IgG2, compared with a single vaccination and IFN-γ levels increased with repeated immunization with UV-irradiated cercariae. The high levels of protection against S. japonicum infection can be achieved with a UV-attenuated vaccine in pigs, and that three vaccinations were possibly more effective than a single vaccination. Moreover, triple vaccinations evoked a more vigorous IFN-γ response and a stronger antibody-mediated response, especially an increase in the levels of IgG2 antibodies.

  19. Representation of categories.

    PubMed

    Boot, Inge; Pecher, Diane

    2011-01-01

    In the present study we investigated whether the mental representation of the concept categories is represented by the container image schema (Lakoff & Johnson, 1980). In two experiments participants decided whether two pictures were from the same category (animal or vehicle). Pictures were presented inside or outside a frame that should activate the container schema. We found that performance to pictures was influenced by the frame in congruence with the metaphorical mapping (same category—inside bounded region; different category—not in same bounded region). These results show that the concept categories is metaphorically represented by containers.

  20. Brain-selective overexpression of angiotensin-converting enzyme 2 attenuates sympathetic nerve activity and enhances baroreflex function in chronic heart failure.

    PubMed

    Xiao, Liang; Gao, Lie; Lazartigues, Eric; Zucker, Irving H

    2011-12-01

    Angiotensin-converting enzyme 2 (ACE2) has been suggested to be involved in the central regulation of autonomic function. During chronic heart failure (CHF), elevated central angiotensin II signaling contributes to the sustained increase of sympathetic outflow. This is accompanied by a downregulation of ACE2 in the brain. We hypothesized that central overexpression of ACE2 decreases sympathetic outflow and enhances baroreflex function in CHF. Transgenic mice overexpressing human ACE2 selectively in the brain (SYN-hACE2 [SA]) and wild-type littermates (WT) were used. CHF was induced by permanent coronary artery ligation. Four weeks after coronary artery ligation, both WT and SA mice exhibited a significant decrease in left ventricular ejection fraction (<40%). A slight decrease in mean arterial pressure was found only in SA mice. Compared with WT mice with CHF, brain-selective ACE2 overexpression attenuated left ventricular end-diastolic pressure; decreased urinary norepinephrine excretion; baseline renal sympathetic nerve activity (WT CHF: 71.6±7.6% max versus SA CHF: 49.3±6.1% max); and enhanced baroreflex sensitivity (maximum slope: WT sham: 1.61±0.16%/mm Hg versus SA CHF: 1.51±0.17%/mm Hg). Chronic subcutaneous blockade of mas receptor increased renal sympathetic nerve activity in SA mice with CHF (A779: 67.3±5.8% versus vehicle: 46.4±3.6% of max). An upregulation in angiotensin II type 1 receptor expression was detected in medullary nuclei in WT CHF mice, which was significantly attenuated in SA mice with CHF. These data suggest that central ACE2 overexpression exerts a potential protective effect in CHF through attenuating sympathetic outflow. The mechanism for this effect involves angiotensin (1-7) mas signaling, as well as a decrease in angiotensin II type 1 receptor signaling in the medulla.

  1. Attenuation by d-limonene of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

    PubMed

    Yano, H; Tatsuta, M; Iishi, H; Baba, M; Sakai, N; Uedo, N

    1999-08-27

    The effects of prolonged administration of d-limonene, a monocyclic monoterpene, on sodium chloride-enhanced induction of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine, the labeling and apoptotic indices, and ornithine decarboxylase (ODC) activity of gastric cancers were investigated in Wistar rats. After 25 weeks of carcinogen treatment, rats were given chow pellets containing 10% sodium chloride and 1% limonene ad libitum. In week 52, the incidence of gastric cancers, the labeling index and ODC activity were significantly higher and the apoptotic index was significantly lower in rats given sodium chlolide than in untreated control rats. However, in rats given both sodium chloride and d-limonene, the incidence of gastric cancers, the labeling index and ODC activity were significantly lower and the apoptotic index was significantly higher than in rats given sodium chloride alone. Our findings suggest that limonene attenuates the gastric carcinogenesis enhanced by sodium chloride via increased apoptosis and decreased ODC activity in gastric cancers.

  2. Knockdown of HIF-1α by siRNA-expressing plasmid delivered by attenuated Salmonella enhances the antitumor effects of cisplatin on prostate cancer.

    PubMed

    Gu, Junlian; Li, Yang; Zeng, Jun; Wang, Bo; Ji, Kun; Tang, Yufeng; Sun, Qing

    2017-08-08

    Resistance to cisplatin (DDP) and dose-related toxicity remain two important obstacles in the treatment of prostate cancer (PCa) patients with DDP-based chemotherapy. We have investigated whether the knockdown of hypoxia-inducible factor-1 alpha (HIF-1α) by siRNA could enhance the antitumor activity of DDP, and aimed to determine the underlying mechanisms. Intravenous injection of attenuated Salmonella carrying a HIF-1α siRNA-expressing plasmid was used to knockdown HIF-1α in a PC-3 xenograft model. The in vitro and in vivo effects of HIF-1α siRNA treatment and/or DPP on PCa cell proliferation, apoptosis, glycolysis, and production of reactive oxygen species (ROS) were assessed by examining molecular markers specific to each process. The results demonstrated that the treatment of tumor-bearing mice with attenuated Salmonella carrying the HIF-1α siRNA plasmid greatly enhanced the antitumor effects of low-dose DDP. Further mechanistic studies demonstrated that knockdown of HIF-1α improved the response of PCa cells to DDP by redirecting aerobic glycolysis toward mitochondrial oxidative phosphorylation, leading to cell death through overproduction of ROS. Our findings indicate that DDP-based chemotherapy combined with targeting the HIF-1α-regulated cancer metabolism pathway might be an ideal strategy to treat PCa.

  3. Elevation of CpG frequencies in influenza A genome attenuates pathogenicity but enhances host response to infection

    PubMed Central

    Gaunt, Eleanor; Wise, Helen M; Zhang, Huayu; Lee, Lian N; Atkinson, Nicky J; Nicol, Marlynne Quigg; Highton, Andrew J; Klenerman, Paul; Beard, Philippa M; Dutia, Bernadette M; Digard, Paul; Simmonds, Peter

    2016-01-01

    Previously, we demonstrated that frequencies of CpG and UpA dinucleotides profoundly influence the replication ability of echovirus 7 (Tulloch et al., 2014). Here, we show that that influenza A virus (IAV) with maximised frequencies of these dinucleotides in segment 5 showed comparable attenuation in cell culture compared to unmodified virus and a permuted control (CDLR). Attenuation was also manifested in vivo, with 10-100 fold reduced viral loads in lungs of mice infected with 200PFU of CpG-high and UpA-high mutants. However, both induced powerful inflammatory cytokine and adaptive (T cell and neutralising antibody) responses disproportionate to their replication. CpG-high infected mice also showed markedly reduced clinical severity, minimal weight loss and reduced immmunopathology in lung, yet sterilising immunity to lethal dose WT challenge was achieved after low dose (20PFU) pre-immunisation with this mutant. Increasing CpG dinucleotide frequencies represents a generic and potentially highly effective method for generating safe, highly immunoreactive vaccines. DOI: http://dx.doi.org/10.7554/eLife.12735.001 PMID:26878752

  4. Phloroglucinol Attenuates Motor Functional Deficits in an Animal Model of Parkinson's Disease by Enhancing Nrf2 Activity

    PubMed Central

    Hong, Bo-Hyun; Yang, Eun-Jung; Kang, Kyoung Ah; Choi, Moonseok; Kim, Ki Cheon; Noh, Su-Jin; Kim, Hee Soo; Lee, Nam-Ho; Hyun, Jin Won; Kim, Hye-Sun

    2013-01-01

    In this study, we investigated whether phloroglucinol (1, 3, 5 - trihydroxybenzene) has therapeutic effects in cellular and animal model of Parkinson's disease (PD). PD is the second most common, chronic and progressive neurodegenerative disease, and is clinically characterized with motor dysfunctions such as bradykinesia, rigidity, postural instability, gait impairment, and resting tremor. In the brains of PD patients, dopaminergic neuronal loss is observed in the Substantia nigra. Although the exact mechanisms underlying PD are largely unknown, mitochondrial dysfunction and oxidative stress are thought to be critical factors that induce the onset of the disease. Here, phloroglucinol administration was shown to attenuate motor functional deficits evaluated with rota-rod and apomorphine-induced rotation tests in 6-hydroxydopamine (6-OHDA)-induced PD animal models. Moreover, phloroglucinol ameliorated the loss of synapses as assessed with protein levels and immunoreactivity against synaptophysin in the midbrain region of the 6-OHDA-lesioned rats. In addition, in SH-SY5Y cultures, the cytotoxicity of 6-OHDA was reduced by pre-treatment with phloroglucinol. The increase in the reactive oxygen species, lipid peroxidation, protein carbonyl formation and 8-hydroxyguanine caused by treatment with 6-OHDA was attenuated by phloroglucinol in SH-SY5Y cells. Furthermore, phloroglucinol treatment rescued the reduced levels of nuclear Nrf2, antioxidant enzymes, i.e., catalase and glutathione peroxidase, in 6-OHDA-treated cells. Taken together, phloroglucinol has a therapeutic potential for treatment of PD. PMID:23976995

  5. Phloroglucinol attenuates motor functional deficits in an animal model of Parkinson's disease by enhancing Nrf2 activity.

    PubMed

    Ryu, Junghwa; Zhang, Rui; Hong, Bo-Hyun; Yang, Eun-Jung; Kang, Kyoung Ah; Choi, Moonseok; Kim, Ki Cheon; Noh, Su-Jin; Kim, Hee Soo; Lee, Nam-Ho; Hyun, Jin Won; Kim, Hye-Sun

    2013-01-01

    In this study, we investigated whether phloroglucinol (1,3,5-trihydroxybenzene) has therapeutic effects in cellular and animal model of Parkinson's disease (PD). PD is the second most common, chronic and progressive neurodegenerative disease, and is clinically characterized with motor dysfunctions such as bradykinesia, rigidity, postural instability, gait impairment, and resting tremor. In the brains of PD patients, dopaminergic neuronal loss is observed in the Substantia nigra. Although the exact mechanisms underlying PD are largely unknown, mitochondrial dysfunction and oxidative stress are thought to be critical factors that induce the onset of the disease. Here, phloroglucinol administration was shown to attenuate motor functional deficits evaluated with rota-rod and apomorphine-induced rotation tests in 6-hydroxydopamine (6-OHDA)-induced PD animal models. Moreover, phloroglucinol ameliorated the loss of synapses as assessed with protein levels and immunoreactivity against synaptophysin in the midbrain region of the 6-OHDA-lesioned rats. In addition, in SH-SY5Y cultures, the cytotoxicity of 6-OHDA was reduced by pre-treatment with phloroglucinol. The increase in the reactive oxygen species, lipid peroxidation, protein carbonyl formation and 8-hydroxyguanine caused by treatment with 6-OHDA was attenuated by phloroglucinol in SH-SY5Y cells. Furthermore, phloroglucinol treatment rescued the reduced levels of nuclear Nrf2, antioxidant enzymes, i.e., catalase and glutathione peroxidase, in 6-OHDA-treated cells. Taken together, phloroglucinol has a therapeutic potential for treatment of PD.

  6. Chlorogenic Acid Attenuates High Mobility Group Box 1 (HMGB1) and Enhances Host Defense Mechanisms in Murine Sepsis

    PubMed Central

    Lee, Chan-Ho; Yoon, Seong-Jin; Lee, Sun-Mee

    2012-01-01

    Sepsis is a complex, multifactorial, rapidly progressive disease characterized by an overwhelming activation of the immune system and the countervailing antiinflammatory response. In the current study in murine peritoneal macrophages, chlorogenic acid suppressed endotoxin-induced high mobility group box 1 (HMGB1) release in a concentration-dependent manner. Administration of chlorogenic acid also attenuated systemic HMGB1 accumulation in vivo and prevented mortality induced by endotoxemia and polymicrobial sepsis. The mechanisms of action of chlorogenic acid included attenuation of the increase in toll-like receptor (TLR)-4 expression and suppression of sepsis-induced signaling pathways, such as c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB, which are critical for cytokine release. The protection conferred by chlorogenic acid was achieved through modulation of cytokine and chemokine release, suppression of immune cell apoptosis and augmentation of bacterial elimination. Chlorogenic acid warrants further evaluation as a potential therapeutic agent for the treatment of sepsis and other potentially fatal systemic inflammatory disorders. PMID:23168580

  7. Winter Day Lengths Enhance T Lymphocyte Phenotypes, Inhibit Cytokine Responses, and Attenuate Behavioral Symptoms of Infection in Laboratory Rats

    PubMed Central

    Prendergast, Brian J.; Kampf-Lassin, August; Yee, Jason R.; Galang, Jerome; McMaster, Nicholas; Kay, Leslie M.

    2009-01-01

    Annual variations in day length (photoperiod) trigger changes in the immune and reproductive system of seasonally-breeding animals. The purpose of this study was to determine whether photoperiodic changes in immunity depend on concurrent photoperiodic responses in the reproductive system, or whether immunological responses to photoperiod occur independent of reproductive responses. Here we report photoperiodic changes in enumerative, functional, and behavioral aspects of the immune system, and in immunomodulatory glucocorticoid secretion, in reproductively non-photoperiodic Wistar rats. T-cell numbers (CD3+, CD8+, CD8+CD25+, CD4+CD25+) were higher in the blood of rats housed in short as opposed to long day lengths for 10 weeks. Following a simulated bacterial infection (E. coli LPS; 125 μg/kg) the severity of several acute-phase sickness behaviors (anorexia, cachexia, neophobia, and social withdrawal) were attenuated in short days. LPS-stimulated IL-1β and IL-6 production were comparable between photoperiods, but plasma TNFα was higher in long-day relative to short-day rats. In addition, corticosterone concentrations were higher in short-day relative to long-day rats. The data are consistent with the hypothesis that photoperiodic regulation of the immune system can occur entirely independently of photoperiodic regulation of the reproductive system. In the absence of concurrent reproductive responses, short days increase the numbers of leukocytes capable of immunosurveillance and inhibition of inflammatory responses, increase proinflammatory cytokine production, increase immunomodulatory glucocorticoid secretion, and ultimately attenuate behavioral responses to infection. Seasonal changes in the host immune system, endocrine system, and behavior may contribute to the seasonal variability in disease outcomes, even in reproductively non-photoperiodic mammals. PMID:17728099

  8. A Brucella melitensis M5-90 wboA deletion strain is attenuated and enhances vaccine efficacy.

    PubMed

    Li, Zhi-Qiang; Shi, Jing-Xue; Fu, Wen-Dong; Zhang, Yu; Zhang, Jing; Wang, Zhen; Li, Tian-Sen; Chen, Chuang-Fu; Guo, Fei; Zhang, Hui

    2015-08-01

    Brucella spp. are Gram-negative intracellular pathogens of both humans and animals that cause great economic burdens in developing countries. Live attenuated vaccines are the most efficient means for the prevention and control of animal Brucellosis. However, Brucella vaccines (strain M5-90 and others) have several drawbacks and do not allow serological differentiation between vaccinated and infected animals. A wboA mutant was derived from Brucella melitensis (B. melitensis) vaccine strain M5-90 and tested for virulence and protective efficiency. T-cell responses (CD4(+), CD8(+)), levels of immunoglobulin G (IgG), and cytokine production were observed. WboA was also assessed as a diagnostic marker for Brucellosis. B. melitensis strain M5-90ΔwboA exhibited reduced survival in murine macrophages (RAW 264.7) and BALB/c mice and induced protective immunity in mice comparable to that from the parental strain M5-90. In mice, the wboA mutant elicited an anti-Brucella-specific IgG response and induced the secretion of gamma interferon (IFN-γ) and interleukin-2 (IL-2). In sheep, M5-90ΔwboA immunization induced the secretion of IFN-γ, and serum samples from sheep inoculated with M5-90ΔwboA were negative by Bengal Plate Test (RBPT) and Standard Tube Agglutination Test (STAT). In mice, probes against WboA antigen allowed for serological differentiation between natural infection and vaccination. The M5-90ΔwboA mutant is a potential attenuated live vaccine candidate against virulent B. melitensis 16M infection. It will be further evaluated in livestock.

  9. Winter day lengths enhance T lymphocyte phenotypes, inhibit cytokine responses, and attenuate behavioral symptoms of infection in laboratory rats.

    PubMed

    Prendergast, Brian J; Kampf-Lassin, August; Yee, Jason R; Galang, Jerome; McMaster, Nicholas; Kay, Leslie M

    2007-11-01

    Annual variations in day length (photoperiod) trigger changes in the immune and reproductive system of seasonally-breeding animals. The purpose of this study was to determine whether photoperiodic changes in immunity depend on concurrent photoperiodic responses in the reproductive system, or whether immunological responses to photoperiod occur independent of reproductive responses. Here we report photoperiodic changes in enumerative, functional, and behavioral aspects of the immune system, and in immunomodulatory glucocorticoid secretion, in reproductively non-photoperiodic Wistar rats. T-cell numbers (CD3+, CD8+, CD8+CD25+, CD4+CD25+) were higher in the blood of rats housed in short as opposed to long-day lengths for 10 weeks. Following a simulated bacterial infection (Escherichia coli LPS; 125 microg/kg) the severity of several acute-phase sickness behaviors (anorexia, cachexia, neophobia, and social withdrawal) were attenuated in short days. LPS-stimulated IL-1beta and IL-6 production were comparable between photoperiods, but plasma TNFalpha was higher in long-day relative to short-day rats. In addition, corticosterone concentrations were higher in short-day relative to long-day rats. The data are consistent with the hypothesis that photoperiodic regulation of the immune system can occur entirely independently of photoperiodic regulation of the reproductive system. In the absence of concurrent reproductive responses, short days increase the numbers of leukocytes capable of immunosurveillance and inhibition of inflammatory responses, increase proinflammatory cytokine production, increase immunomodulatory glucocorticoid secretion, and ultimately attenuate behavioral responses to infection. Seasonal changes in the host immune system, endocrine system, and behavior may contribute to the seasonal variability in disease outcomes, even in reproductively non-photoperiodic mammals.

  10. Phonetic category recalibration: What are the categories?

    PubMed Central

    Reinisch, Eva; Wozny, David R.; Mitterer, Holger; Holt, Lori L.

    2014-01-01

    Listeners use lexical or visual context information to recalibrate auditory speech perception. After hearing an ambiguous auditory stimulus between /aba/ and /ada/ coupled with a clear visual stimulus (e.g., lip closure in /aba/), an ambiguous auditory-only stimulus is perceived in line with the previously seen visual stimulus. What remains unclear, however, is what exactly listeners are recalibrating: phonemes, phone sequences, or acoustic cues. To address this question we tested generalization of visually-guided auditory recalibration to 1) the same phoneme contrast cued differently (i.e., /aba/-/ada/ vs. /ibi/-/idi/ where the main cues are formant transitions in the vowels vs. burst and frication of the obstruent), 2) a different phoneme contrast cued identically (/aba/-/ada/ vs. /ama/-/ana/ both cued by formant transitions in the vowels), and 3) the same phoneme contrast with the same cues in a different acoustic context (/aba/-/ada/ vs. (/ubu/-/udu/). Whereas recalibration was robust for all recalibration control trials, no generalization was found in any of the experiments. This suggests that perceptual recalibration may be more specific than previously thought as it appears to be restricted to the phoneme category experienced during exposure as well as to the specific manipulated acoustic cues. We suggest that recalibration affects context-dependent sub-lexical units. PMID:24932053

  11. Pericortical Enhancement on Delayed Postgadolinium Fluid-Attenuated Inversion Recovery Images in Normal Aging, Mild Cognitive Impairment, and Alzheimer Disease.

    PubMed

    Freeze, W M; Schnerr, R S; Palm, W M; Jansen, J F; Jacobs, H I; Hoff, E I; Verhey, F R; Backes, W H

    2017-09-01

    Breakdown of BBB integrity occurs in dementia and may lead to neurodegeneration and cognitive decline. We assessed whether extravasation of gadolinium chelate could be visualized on delayed postcontrast FLAIR images in older individuals with and without cognitive impairment. Seventy-four individuals participated in this study (15 with Alzheimer disease, 33 with mild cognitive impairment, and 26 with normal cognition). We assessed the appearance of pericortical enhancement after contrast administration, MR imaging markers of cerebrovascular damage, and medial temporal lobe atrophy. Three participants who were positive for pericortical enhancement (1 with normal cognition and 2 with mild cognitive impairment) were followed up for approximately 2 years. In vitro experiments with a range of gadolinium concentrations served to elucidate the mechanisms underlying the postcontrast FLAIR signals. Postcontrast pericortical enhancement was observed in 21 participants (28%), including 6 individuals with Alzheimer disease (40%), 10 with mild cognitive impairment (30%), and 5 with normal cognition (19%). Pericortical enhancement was positively associated with age (P < .02) and ischemic stroke (P < .05), but not with cognitive status (P = .3). Foci with enhanced signal remained stable across time in all follow-up cases. The in vitro measurements confirmed that FLAIR imaging is highly sensitive for the detection of low gadolinium concentrations in CSF, but not in cerebral tissue. Postcontrast pericortical enhancement on FLAIR images occurs in older individuals with normal cognition, mild cognitive impairment, and dementia. It may represent chronic focal superficial BBB leakage. Future longitudinal studies are needed to determine its clinical significance. © 2017 by American Journal of Neuroradiology.

  12. Flurbiprofen Axetil Enhances Analgesic Effects of Sufentanil and Attenuates Postoperative Emergence Agitation and Systemic Proinflammation in Patients Undergoing Tangential Excision Surgery.

    PubMed

    Geng, Wujun; Hong, Wandong; Wang, Junlu; Dai, Qinxue; Mo, Yunchang; Shi, Kejian; Sun, Jiehao; Qin, Jinling; Li, Mei; Tang, Hongli

    2015-01-01

    Our present study tested whether flurbiprofen axetil could reduce perioperative sufentanil consumption and provide postoperative analgesia with decrease in emergency agitation and systemic proinflammatory cytokines release. Ninety patients undergoing tangential excision surgery were randomly assigned to three groups: (1) preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 μg/kg sufentanil and 10 mL placebo by patient-controlled analgesia (PCA) pump, (2) preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 μg/kg sufentanil and 100 mg flurbiprofen axetil by PCA pump, and (3) 10 mL placebo and a postoperative dose of 2 μg/kg sufentanil and 10 mL placebo by PCA pump. Preoperative administration of flurbiprofen axetil decreased postoperative tramadol consumption and the visual analog scale at 4, 6, 12, and 24 h after surgery, which were further decreased by postoperative administration of flurbiprofen axetil. Furthermore, flurbiprofen axetil attenuated emergency agitation score and Ramsay score at 0, 5, and 10 min after extubation and reduced the TNF-α and interleukin- (IL-) 6 levels at 24 and 48 h after the operation. Flurbiprofen axetil enhances analgesic effects of sufentanil and attenuates emergence agitation and systemic proinflammation in patients undergoing tangential excision surgery.

  13. Consumer Product Category Database

    EPA Pesticide Factsheets

    The Chemical and Product Categories database (CPCat) catalogs the use of over 40,000 chemicals and their presence in different consumer products. The chemical use information is compiled from multiple sources while product information is gathered from publicly available Material Safety Data Sheets (MSDS). EPA researchers are evaluating the possibility of expanding the database with additional product and use information.

  14. A tryptamine-derived catecholaminergic enhancer, (-)-1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP], attenuates reinstatement of methamphetamine-seeking behavior in rats.

    PubMed

    Hiranita, T; Yamamoto, T; Nawata, Y

    2010-01-20

    Relapse to drug craving is problematic in treatment for drug abuse. Evidence suggests inactivation of dopaminergic neurotransmission during drug withdrawal. Meanwhile, a tryptamine analogue, (-)-1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP], has been reported to enhance electrical stimulation of monoamine release. This study examined the effect of (-)-BPAP on reinstatement of methamphetamine-seeking behavior in an animal model of relapse to drug abuse. Rats were trained to i.v. self-administer methamphetamine paired with a light and tone (methamphetamine-associated cues) under a fixed-ratio 1 schedule of reinforcement for 10 days. After extinction session under saline infusions without cues, a reinstatement test under saline infusions was begun. Reinstatement induced by methamphetamine-associated cues or methamphetamine-priming injections was attenuated by repeated administration of (-)-BPAP during the extinction phase. Acute administration of (-)-BPAP on test day dose-dependently attenuated both reinstatements. Acute administration of (-)-BPAP neither reinstated methamphetamine-seeking behavior alone nor affected methamphetamine self-administration. Pretreatment with either R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH-23390), a dopamine D(1)-like receptor antagonist, or amisulpride, a dopamine D(2)-like receptor antagonist, did not appreciably affected the acute effect of (-)-BPAP on both reinstatements. Co-pretreatment with the dopamine receptor antagonists failed to alter the effects of (-)-BPAP. Meanwhile, pretreatment with a dopamine D(1)-like receptor agonist, (+/-)-6-chloro-7,8-dihydroxy-l-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF-81297), dose-dependently attenuated reinstatement induced by the cues or methamphetamine-priming injections. In contrast to (-)-BPAP, pretreatment with SCH-23390 reversed the effects of SKF-81297. Our findings suggest activation of dopamine D(1)-like receptors results

  15. LcrV delivered via type III secretion system of live attenuated Yersinia pseudotuberculosis enhances immunogenicity against pneumonic plague.

    PubMed

    Sun, Wei; Sanapala, Shilpa; Henderson, Jeremy C; Sam, Shandiin; Olinzock, Joseph; Trent, M Stephen; Curtiss, Roy

    2014-10-01

    Here, we constructed a Yersinia pseudotuberculosis mutant strain with arabinose-dependent regulated and delayed shutoff of crp expression (araC P(BAD) crp) and replacement of the msbB gene with the Escherichia coli msbB gene to attenuate it. Then, we inserted the asd mutation into this construction to form χ10057 [Δasd-206 ΔmsbB868::P(msbB) msbB(EC) ΔP(crp21)::TT araC P(BAD) crp] for use with a balanced-lethal Asd-positive (Asd(+)) plasmid to facilitate antigen synthesis. A hybrid protein composed of YopE (amino acids [aa]1 to 138) fused with full-length LcrV (YopE(Nt138)-LcrV) was synthesized in χ10057 harboring an Asd(+) plasmid (pYA5199, yopE(Nt138)-lcrV) and could be secreted through a type III secretion system (T3SS) in vitro and in vivo. Animal studies indicated that mice orally immunized with χ10057(pYA5199) developed titers of IgG response to whole-cell lysates of Y. pestis (YpL) and subunit LcrV similar to those seen with χ10057(pYA3332) (χ10057 plus an empty plasmid). However, only immunization of mice with χ10057(pYA5199) resulted in a significant secretory IgA response to LcrV. χ10057(pYA5199) induced a higher level of protection (80% survival) against intranasal (i.n.) challenge with ~240 median lethal doses (LD50) (2.4 × 10(4) CFU) of Y. pestis KIM6+(pCD1Ap) than χ10057(pYA3332) (40% survival). Splenocytes from mice vaccinated with χ10057(pYA5199) produced significant levels of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-17 (IL-17) after restimulation with LcrV and YpL antigens. Our results suggest that it is possible to use an attenuated Y. pseudotuberculosis strain delivering the LcrV antigen via the T3SS as a potential vaccine candidate against pneumonic plague. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  16. PRELIMINARY DATA REPORT: HUMATE INJECTION AS AN ENHANCED ATTENUATION METHOD AT THE F-AREA SEEPAGE BASINS, SAVANNAH RIVER SITE

    SciTech Connect

    Millings, M.

    2013-09-16

    A field test of a humate technology for uranium and I-129 remediation was conducted at the F-Area Field Research Site as part of the Attenuation-Based Remedies for the Subsurface Applied Field Research Initiative (ABRS AFRI) funded by the DOE Office of Soil and Groundwater Remediation. Previous studies have shown that humic acid sorbed to sediments strongly binds uranium at mildly acidic pH and potentially binds iodine-129 (I-129). Use of humate could be applicable for contaminant stabilization at a wide variety of DOE sites however pilot field-scale tests and optimization of this technology are required to move this technical approach from basic science to actual field deployment and regulatory acceptance. The groundwater plume at the F-Area Field Research Site contains a large number of contaminants, the most important from a risk perspective being strontium-90 (Sr-90), uranium isotopes, I-129, tritium, and nitrate. Groundwater remains acidic, with pH as low as 3.2 near the basins and increasing to the background pH of approximately 5at the plume fringes. The field test was conducted in monitoring well FOB 16D, which historically has shown low pH and elevated concentrations of Sr-90, uranium, I-129 and tritium. The field test included three months of baseline monitoring followed by injection of a potassium humate solution and approximately four and half months of post monitoring. Samples were collected and analyzed for numerous constituents but the focus was on attenuation of uranium, Sr-90, and I-129. This report provides background information, methodology, and preliminary field results for a humate field test. Results from the field monitoring show that most of the excess humate (i.e., humate that did not sorb to the sediments) has flushed through the surrounding formation. Furthermore, the data indicate that the test was successful in loading a band of sediment surrounding the injection point to a point where pH could return to near normal during the study

  17. Mycobacterium tuberculosis PE_PGRS18 enhances the intracellular survival of M. smegmatis via altering host macrophage cytokine profiling and attenuating the cell apoptosis.

    PubMed

    Yang, Wenmin; Deng, Wanyan; Zeng, Jie; Ren, Sai; Ali, Md Kaisar; Gu, Yinzhong; Li, Yangyuling; Xie, Jianping

    2017-04-01

    Mycobacterium tuberculosis PE/PPE family proteins, named after the presence of conserved PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains at N-terminal, are prevalent in M. tuberculosis genome. The function of most PE/PPE family proteins remains elusive. To characterize the function of PE_PGRS18, the encoding gene was heterologously expressed in M. smegmatis, a nonpathogenic mycobacterium. The recombinant PE_PGRS18 is cell wall associated. M. smegmatis PE_PGRS18 recombinant showed differential response to stresses and altered the production of host cytokines IL-6, IL-1β, IL-12p40 and IL-10, as well as enhanced survival within macrophages largely via attenuating the apoptosis of macrophages. In summary, the study firstly unveiled the role of PE_PGRS18 in physiology and pathogenesis of mycobacterium.

  18. Simplicial Descent Categories

    NASA Astrophysics Data System (ADS)

    Rodriguez Gonzalez, Beatriz

    2008-04-01

    Much of the homotopical and homological structure of the categories of chain complexes and topological spaces can be deduced from the existence and properties of the 'simple' functors Tot : {double chain complexes} -> {chain complexes} and geometric realization : {sSets} -> {Top}, or similarly, Tot : {simplicial chain complexes} -> {chain complexes} and | | : {sTop} -> {Top}. The purpose of this thesis is to abstract this situation, and to this end we introduce the notion of '(co)simplicial descent category'. It is inspired by Guillen-Navarros's '(cubical) descent categories'. The key ingredients in a (co)simplicial descent category D are a class E of morphisms in D, called equivalences, and a 'simple' functor s : {(co)simplicial objects in D} -> D. They must satisfy axioms like 'Eilenberg-Zilber', 'exactness' and 'acyclicity'. This notion covers a wide class of examples, as chain complexes, sSets, topological spaces, filtered cochain complexes (where E = filtered quasi-isomorphisms or E = E_2-isomorphisms), commutative differential graded algebras (with s = Navarro's Thom-Whitney simple), DG-modules over a DG-category and mixed Hodge complexes, where s = Deligne's simple. From the simplicial descent structure we obtain homotopical structure on D, as cone and cylinder objects. We use them to i) explicitly describe the morphisms of HoD=D[E^{-1}] similarly to the case of calculus of fractions; ii) endow HoD with a non-additive pre-triangulated structure, that becomes triangulated in the stable additive case. These results use the properties of a 'total functor', which associates to any biaugmented bisimplicial object a simplicial object. It is the simplicial analogue of the total chain complex of a double complex, and it is left adjoint to Illusie's 'decalage' functor.

  19. Epigenetic Upregulation of Metallothionein 2A by Diallyl Trisulfide Enhances Chemosensitivity of Human Gastric Cancer Cells to Docetaxel Through Attenuating NF-κB Activation

    PubMed Central

    Pan, Yuanming; Lin, Shuye; Xing, Rui; Zhu, Min; Lin, Bonan; Cui, Jiantao; Li, Wenmei; Gao, Jing; Shen, Lin; Zhao, Yuanyuan; Guo, Mingzhou; Wang, Ji Ming

    2016-01-01

    Abstract Aims: Metallothionein 2A (MT2A) and nuclear factor-kappaB (NF-κB) are both involved in carcinogenesis and cancer chemosensitivity. We previously showed decreased expression of MT2A and IκB-α in human gastric cancer (GC) associated with poor prognosis of GC patients. The present study investigated the effect of diallyl trisulfide (DATS), a garlic-derived compound, and docetaxel (DOC) on regulation of MT2A in relation to NF-κB in GC cells. Results: DATS attenuated NF-κB signaling in GC cells, resulting in G2/M cell cycle arrest and apoptosis, culminating in the inhibition of cell proliferation and tumorigenesis in nude mice. The anti-GC effect of DATS was attributable to its capacity to epigenetically upregulate MT2A, which in turn enhanced transcription of IκB-α to suppress NF-κB activation in GC cells. The combination of DATS with DOC exhibited a synergistic anti-GC activity accompanied by MT2A upregulation and NF-κB inactivation. Histopathologic analysis of GC specimens from patients showed a significant increase in MT2A expression following DOC treatment. GC patients with high MT2A expression in tumor specimens showed significantly improved response to chemotherapy and prolonged survival compared with those with low MT2A expression in tumors. Innovation and Conclusion: We conclude that DATS exerts its anti-GC activity and enhances chemosensitivity of GC to DOC by epigenetic upregulation of MT2A to attenuate NF-κB signaling. Our findings delineate a mechanistic basis of MT2A/NF-κB signaling for DATS- and DOC-mediated anti-GC effects, suggesting that MT2A may be a chemosensitivity indicator in GC patients receiving DOC-based treatment and a promising target for more effective treatment of GC by combination of DATS and DOC. Antioxid. Redox Signal. 24, 839–854. PMID:26801633

  20. Light attenuates lipid accumulation while enhancing cell proliferation and starch synthesis in the glucose-fed oleaginous microalga Chlorella zofingiensis.

    PubMed

    Chen, Tianpeng; Liu, Jin; Guo, Bingbing; Ma, Xiaonian; Sun, Peipei; Liu, Bin; Chen, Feng

    2015-10-07

    The objective of this study was to investigate the effect of light on lipid and starch accumulation in the oleaginous green algae Chlorella zofingiensis supplemented with glucose. C. zofingiensis, when fed with 30 g/L glucose, synthesized lipids up to 0.531 g/g dry weight; while in the presence of light, the lipid content dropped down to 0.352 g/g dry weight. Lipid yield on glucose was 0.184 g/g glucose, 14% higher than that cultured with light. The light-mediated lipid reduction was accompanied by the down-regulation of fatty acid biosynthetic genes at the transcriptional level. Furthermore, light promoted cell proliferation, starch accumulation, and the starch yield based on glucose. Taken together, light may attenuate lipid accumulation, possibly through the inhibition of lipid biosynthetic pathway, leading to more carbon flux from glucose to starch. This study reveals the dual effects of light on the sugar-fed C. zofingiensis and provides valuable insights into the possible optimization of algal biomass and lipid production by manipulation of culture conditions.

  1. A DJ-1 Based Peptide Attenuates Dopaminergic Degeneration in Mice Models of Parkinson's Disease via Enhancing Nrf2

    PubMed Central

    Lev, Nirit; Barhum, Yael; Ben-Zur, Tali; Aharony, Israel; Trifonov, Lena; Regev, Noa; Melamed, Eldad; Gruzman, Arie; Offen, Daniel

    2015-01-01

    Drugs currently used for treating Parkinson's disease patients provide symptomatic relief without altering the neurodegenerative process. Our aim was to examine the possibility of using DJ-1 (PARK7), as a novel therapeutic target for Parkinson's disease. We designed a short peptide, named ND-13. This peptide consists of a 13 amino acids segment of the DJ-1-protein attached to 7 amino acids derived from TAT, a cell penetrating protein. We examined the effects of ND-13 using in vitro and in vivo experimental models of Parkinson's disease. We demonstrated that ND-13 protects cultured cells against oxidative and neurotoxic insults, reduced reactive oxygen species accumulation, activated the protective erythroid-2 related factor 2 system and increased cell survival. ND-13 robustly attenuated dopaminergic system dysfunction and in improved the behavioral outcome in the 6-hydroxydopamine mouse model of Parkinson's disease, both in wild type and in DJ-1 knockout mice. Moreover, ND-13 restored dopamine content in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model. These findings validate DJ-1 as a promising therapeutic target in Parkinson's disease and identify a novel peptide with clinical potential, which may be significant for a broader range of neurological diseases, possibly with an important impact for the neurosciences. PMID:26024237

  2. Light attenuates lipid accumulation while enhancing cell proliferation and starch synthesis in the glucose-fed oleaginous microalga Chlorella zofingiensis

    PubMed Central

    Chen, Tianpeng; Liu, Jin; Guo, Bingbing; Ma, Xiaonian; Sun, Peipei; Liu, Bin; Chen, Feng

    2015-01-01

    The objective of this study was to investigate the effect of light on lipid and starch accumulation in the oleaginous green algae Chlorella zofingiensis supplemented with glucose. C. zofingiensis, when fed with 30 g/L glucose, synthesized lipids up to 0.531 g/g dry weight; while in the presence of light, the lipid content dropped down to 0.352 g/g dry weight. Lipid yield on glucose was 0.184 g/g glucose, 14% higher than that cultured with light. The light-mediated lipid reduction was accompanied by the down-regulation of fatty acid biosynthetic genes at the transcriptional level. Furthermore, light promoted cell proliferation, starch accumulation, and the starch yield based on glucose. Taken together, light may attenuate lipid accumulation, possibly through the inhibition of lipid biosynthetic pathway, leading to more carbon flux from glucose to starch. This study reveals the dual effects of light on the sugar-fed C. zofingiensis and provides valuable insights into the possible optimization of algal biomass and lipid production by manipulation of culture conditions. PMID:26442783

  3. RGD Peptide Cell-Surface Display Enhances the Targeting and Therapeutic Efficacy of Attenuated Salmonella-mediated Cancer Therapy

    PubMed Central

    Park, Seung-Hwan; Zheng, Jin Hai; Nguyen, Vu Hong; Jiang, Sheng-Nan; Kim, Dong-Yeon; Szardenings, Michael; Min, Jung Hyun; Hong, Yeongjin; Choy, Hyon E.; Min, Jung-Joon

    2016-01-01

    Bacteria-based anticancer therapies aim to overcome the limitations of current cancer therapy by actively targeting and efficiently removing cancer. To achieve this goal, new approaches that target and maintain bacterial drugs at sufficient concentrations during the therapeutic window are essential. Here, we examined the tumor tropism of attenuated Salmonella typhimurium displaying the RGD peptide sequence (ACDCRGDCFCG) on the external loop of outer membrane protein A (OmpA). RGD-displaying Salmonella strongly bound to cancer cells overexpressing αvβ3, but weakly bound to αvβ3-negative cancer cells, suggesting the feasibility of displaying a preferential homing peptide on the bacterial surface. In vivo studies revealed that RGD-displaying Salmonellae showed strong targeting efficiency, resulting in the regression in αvβ3-overexpressing cancer xenografts, and prolonged survival of mouse models of human breast cancer (MDA-MB-231) and human melanoma (MDA-MB-435). Thus, surface engineering of Salmonellae to display RGD peptides increases both their targeting efficiency and therapeutic effect. PMID:27446500

  4. RGD Peptide Cell-Surface Display Enhances the Targeting and Therapeutic Efficacy of Attenuated Salmonella-mediated Cancer Therapy.

    PubMed

    Park, Seung-Hwan; Zheng, Jin Hai; Nguyen, Vu Hong; Jiang, Sheng-Nan; Kim, Dong-Yeon; Szardenings, Michael; Min, Jung Hyun; Hong, Yeongjin; Choy, Hyon E; Min, Jung-Joon

    2016-01-01

    Bacteria-based anticancer therapies aim to overcome the limitations of current cancer therapy by actively targeting and efficiently removing cancer. To achieve this goal, new approaches that target and maintain bacterial drugs at sufficient concentrations during the therapeutic window are essential. Here, we examined the tumor tropism of attenuated Salmonella typhimurium displaying the RGD peptide sequence (ACDCRGDCFCG) on the external loop of outer membrane protein A (OmpA). RGD-displaying Salmonella strongly bound to cancer cells overexpressing αvβ3, but weakly bound to αvβ3-negative cancer cells, suggesting the feasibility of displaying a preferential homing peptide on the bacterial surface. In vivo studies revealed that RGD-displaying Salmonellae showed strong targeting efficiency, resulting in the regression in αvβ3-overexpressing cancer xenografts, and prolonged survival of mouse models of human breast cancer (MDA-MB-231) and human melanoma (MDA-MB-435). Thus, surface engineering of Salmonellae to display RGD peptides increases both their targeting efficiency and therapeutic effect.

  5. Troxerutin Attenuates Enhancement of Hepatic Gluconeogenesis by Inhibiting NOD Activation-Mediated Inflammation in High-Fat Diet-Treated Mice

    PubMed Central

    Zhang, Zifeng; Wang, Xin; Zheng, Guihong; Shan, Qun; Lu, Jun; Fan, Shaohua; Sun, Chunhui; Wu, Dongmei; Zhang, Cheng; Su, Weitong; Sui, Junwen; Zheng, Yuanlin

    2016-01-01

    Recent evidence suggests that troxerutin, a trihydroxyethylated derivative of natural bioflavonoid rutin, exhibits beneficial effects on diabetes-related symptoms. Here we investigated the effects of troxerutin on the enhancement of hepatic gluconeogenesis in high-fat diet (HFD)-treated mice and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + Troxerutin group, and Troxerutin group. Troxerutin was treated by daily oral administration at doses of 150 mg/kg/day for 20 weeks. Tauroursodeoxycholic acid (TUDCA) was used to inhibit endoplasmic reticulum stress (ER stress). Our results showed that troxerutin effectively improved obesity and related metabolic parameters, and liver injuries in HFD-treated mouse. Furthermore, troxerutin significantly attenuated enhancement of hepatic gluconeogenesis in HFD-fed mouse. Moreover, troxerutin notably suppressed nuclear factor-κB (NF-κB) p65 transcriptional activation and release of inflammatory cytokines in HFD-treated mouse livers. Mechanismly, troxerutin dramatically decreased Nucleotide oligomerization domain (NOD) expression, as well as interaction between NOD1/2 with interacting protein-2 (RIP2), by abating oxidative stress-induced ER stress in HFD-treated mouse livers, which was confirmed by TUDCA treatment. These improvement effects of troxerutin on hepatic glucose disorders might be mediated by its anti-obesity effect. In conclusion, troxerutin markedly diminished HFD-induced enhancement of hepatic gluconeogenesis via its inhibitory effects on ER stress-mediated NOD activation and consequent inflammation, which might be mediated by its anti-obesity effect. PMID:28029143

  6. Attenuation of polyglutamine-induced toxicity by enhancement of mitochondrial OXPHOS in yeast and fly models of aging

    PubMed Central

    Ruetenik, Andrea L.; Ocampo, Alejandro; Ruan, Kai; Zhu, Yi; Li, Chong; Zhai, R. Grace; Barrientos, Antoni

    2016-01-01

    Defects in mitochondrial biogenesis and function are common in many neurodegenerative disorders, including Huntington’s disease (HD). We have previously shown that in yeast models of HD, enhancement of mitochondrial biogenesis through overexpression of Hap4, the catalytic subunit of the transcriptional complex that regulates mitochondrial gene expression, alleviates the growth arrest induced by expanded polyglutamine (polyQ) tract peptides in rapidly dividing cells. However, the mechanism through which HAP4 overexpression exerts this protection remains unclear. Furthermore, it remains unexplored whether HAP4 overexpression and increased respiratory function during growth can also protect against polyQ-induced toxicity during yeast chronological lifespan. Here, we show that in yeast, mitochondrial respiration and oxidative phosphorylation (OXPHOS) are essential for protection against the polyQ-induced growth defect by HAP4 overexpression. In addition, we show that not only increased HAP4 levels, but also alternative interventions, including calorie restriction, that result in enhanced mitochondrial biogenesis confer protection against polyQ toxicity during stationary phase. The data obtained in yeast models guided experiments in a fly model of HD, where we show that enhancement of mitochondrial biogenesis can also protect against neurodegeneration and behavioral deficits. Our results suggest that therapeutic interventions aiming at the enhancement of mitochondrial respiration and OXPHOS could reduce polyQ toxicity and delay disease onset. PMID:28357370

  7. Ebselen attenuates oxidative DNA damage and enhances its repair activity in the thalamus after focal cortical infarction in hypertensive rats.

    PubMed

    He, Meixia; Xing, Shihui; Yang, Bo; Zhao, Liqun; Hua, Haiying; Liang, Zhijian; Zhou, Wenliang; Zeng, Jinsheng; Pei, Zhong

    2007-11-21

    Oxidative DNA damage has been proposed to be a major contributor to focal cerebral ischemic injury. However, little is known about the role of oxidative DNA damage in remote damage secondary to the primary infarction. In the present study, we investigated oxidative damage within the ventroposterior nucleus (VPN) after distal middle cerebral artery occlusion (MCAO) in hypertensive rats. We also examined the possible protective effect of ebselen, one glutathione peroxidase mimic, on delayed degeneration in the VPN after distal MCAO. Neuronal damage in the ipsilateral VPN was examined by Nissl staining. Oxidative DNA damage and base repair enzyme activity were assessed by analyzing immunoreactivity of 8-hydroxy-2'-deoxyguanosine (8-ohdG) and 8-oxoguanine DNA glycosylase (OGG1), respectively. The number of intact neurons in the ipsilateral VPN decreased by 52% compared to the contralateral side in ischemia group 2 weeks after distal cerebral cortical infarction. The immunoreactivity of 8-ohdG significantly increased while OGG1 immunoreactivity significantly decreased in the ipsilateral VPN 2 weeks after distal cortical infarction (all p<0.01). Compared with vehicle treatment, ebselen significantly attenuated the neuron loss, ameliorated ischemia-induced increase in 8-ohdG level as well as decrease in OGG1 level within the ipsilateral VPN (all p<0.01). OGG1 was further demonstrated to mainly express in neurons. These findings strongly suggest that oxidative DNA damage may be involved in the delayed neuronal death in the VPN region following distal MCAO. Furthermore, ebselen protects against the delayed damage in the VPN when given at 24 h following distal MCAO.

  8. Hyperbaric oxygen preconditioning attenuates hyperglycemia-enhanced hemorrhagic transformation by inhibiting matrix metalloproteinases in focal cerebral ischemia in rats.

    PubMed

    Soejima, Yoshiteru; Hu, Qin; Krafft, Paul R; Fujii, Mutsumi; Tang, Jiping; Zhang, John H

    2013-09-01

    Hyperglycemia dramatically aggravates brain infarct and hemorrhagic transformation (HT) after ischemic stroke. Oxidative stress and matrix metalloproteinases (MMPs) play an important role in the pathophysiology of HT. Hyperbaric oxygen preconditioning (HBO-PC) has been proved to decrease oxidative stress and has been demonstrated to be neuroprotective in experimental stroke models. The present study determined whether HBO-PC would ameliorate HT by a pre-ischemic increase of reactive oxygen species (ROS) generation, and a suppression of MMP-2 and MMP-9 in hyperglycemic middle cerebral artery occlusion (MCAO) rats. Rats were pretreated with HBO (100% O₂, 2.5 atmosphere absolutes) 1 h daily for 5 days before MCAO. Acute hyperglycemia was induced by an injection of 50% dextrose. Neurological deficits, infarction volume and hemorrhagic volume were assessed 24 h and 7 days after ischemia. ROS scavenger n-acetyl cysteine (NAC), hypoxia-inducible factor-1α (HIF-1α), inhibitor 2-methoxyestradiol (2ME2) and activator cobalt chloride (CoCl₂), and MMP inhibitor SB-3CT were administrated for mechanism study. The activity of MMP-2 and MMP-9, and the expression HIF-1α were measured. HBO-PC improved neurological deficits, and reduced hemorrhagic volume; the expression of HIF-1α was significantly decreased, and the activity of MMP-2 and MMP-9 was reduced by HBO-PC compared with vehicle group. Our results suggested that HBO-PC attenuated HT via decreasing HIF-1α and its downstream MMP-2 and MMP-9 in hyperglycemic MCAO rats.

  9. Restricted Inter-ocean Exchange and Attenuated Biological Export Caused Enhanced Carbonate Preservation in the PETM Ocean

    NASA Astrophysics Data System (ADS)

    Luo, Y.; Boudreau, B. P.; Dickens, G. R.; Sluijs, A.; Middelburg, J. J.

    2015-12-01

    Carbon dioxide (CO2) release during the Paleocene-Eocene Thermal Maximum (PETM, 55.8 Myr BP) acidified the oceans, causing a decrease in calcium carbonate (CaCO3) preservation. During the subsequent recovery from this acidification, the sediment CaCO3 content came to exceed pre-PETM values, known as over-deepening or over-shooting. Past studies claim to explain these trends, but have failed to reproduce quantitatively the time series of CaCO3 preservation. We employ a simple biogeochemical model to recreate the CaCO3 records preserved at Walvis Ridge of the Atlantic Ocean. Replication of the observed changes, both shallowing and the subsequent over-deepening, requires two conditions not previously considered: (1) limited deep-water exchange between the Indo-Atlantic and Pacific oceans and (2) a ~50% reduction in the export of CaCO3 to the deep sea during acidification. Contrary to past theories that attributed over-deepening to increased riverine alkalinity input, we find that over-deepening is an emergent property, generated at constant riverine input when attenuation of CaCO3 export causes an unbalanced alkalinity input to the deep oceans (alkalinization) and the development of deep super-saturation. Restoration of CaCO3 export, particularly in the super-saturated deep Indo-Atlantic ocean, later in the PETM leads to greater accumulation of carbonates, ergo over-shooting, which returns the ocean to pre-PETM conditions over a time scale greater than 200 kyr. While this feedback between carbonate export and the riverine input has not previously been considered, it appears to constitute an important modification of the classic carbonate compensation concept used to explain oceanic response to acidification.

  10. Category specific semantic impairments.

    PubMed

    Warrington, E K; Shallice, T

    1984-09-01

    We report a quantitative investigation of the visual identification and auditory comprehension deficits of 4 patients who had made a partial recovery from herpes simplex encephalitis. Clinical observations had suggested the selective impairment and selective preservation of certain categories of visual stimuli. In all 4 patients a significant discrepancy between their ability to identify inanimate objects and inability to identify living things and foods was demonstrated. In 2 patients it was possible to compare visual and verbal modalities and the same pattern of dissociation was observed in both. For 1 patient, comprehension of abstract words was significantly superior to comprehension of concrete words. Consistency of responses was recorded within a modality in contrast to a much lesser degree of consistency between modalities. We interpret our findings in terms of category specificity in the organization of meaning systems that are also modality specific semantic systems.

  11. Au@Pt nanoparticles as catalase mimics to attenuate tumor hypoxia and enhance immune cell-mediated cytotoxicity.

    PubMed

    Li, Juan; Liang, Hong; Wu, Ying; Ou, Xiang-Yu; Li, Jingying

    2017-09-19

    Hypoxic tumor microenvironment (TME) is closely linked to tumor progression, heterogeneity and immune suppression. Therefore, the development of effective methods to overcome hypoxia and substantially enhance the immunotherapy efficacy remains a desirable goal. Herein, we engineered a biocompatible Au core/Pt shell nanoparticles (Au@Pt NPs) to reoxygenate the TME by reacting with endogenous H2O2. Treatment with Au@Pt NPs appeared to improve oxygen in intracellular environments and decrease hypoxia-inducible factor (HIF)-1α expression. Furthermore, the integration of high catalytic efficiency of Au@Pt NPs with cytokine-induced killer (CIK) cell immunotherapy, could lead to significantly improve the effect of CIK cell-mediated cytotoxicity. These results suggest great potential of Au@Pt NPs for regulation of the hypoxic TME and enhance immune cell mediated anti-tumor immunity. © 2017 IOP Publishing Ltd.

  12. Sound categories or phonemes?

    PubMed

    Redford, Melissa A

    2017-02-01

    Vihman emphasizes the importance of early word production to the emergence of phonological knowledge. This emphasis, consistent with the generative function of phonology, provides insight into the concurrent representation of phonemes and words. At the same time, Vihman's focus on phonology leads her to possibly overstate the influence of early word acquisition on the emergence of sound categories that are probably purely phonetic in nature at the outset of learning.

  13. Quantification of traumatic meningeal injury using dynamic contrast enhanced (DCE) fluid-attenuated inversion recovery (FLAIR) imaging

    NASA Astrophysics Data System (ADS)

    Castro, Marcelo A.; Williford, Joshua P.; Cota, Martin R.; MacLaren, Judy M.; Dardzinski, Bernard J.; Latour, Lawrence L.; Pham, Dzung L.; Butman, John A.

    2016-03-01

    Traumatic meningeal injury is a novel imaging marker of traumatic brain injury, which appears as enhancement of the dura on post-contrast T2-weighted FLAIR images, and is likely associated with inflammation of the meninges. Dynamic Contrast Enhanced MRI provides a better discrimination of abnormally perfused regions. A method to properly identify those regions is presented. Images of seventeen patients scanned within 96 hours of head injury with positive traumatic meningeal injury were normalized and aligned. The difference between the pre- and last post-contrast acquisitions was segmented and voxels in the higher class were spatially clustered. Spatial and morphological descriptors were used to identify the regions of enhancement: a) centroid; b) distance to the brain mask from external voxels; c) distance from internal voxels; d) size; e) shape. The method properly identified thirteen regions among all patients. The method failed in one case due to the presence of a large brain lesion that altered the mask boundaries. Most false detections were correctly rejected resulting in a sensitivity and specificity of 92.9% and 93.6%, respectively.

  14. Conjugated linoleic acid enhances glutathione synthesis and attenuates pathological signs in MRL/MpJ-Fas(lpr) mice.

    PubMed

    Bergamo, Paolo; Luongo, Diomira; Maurano, Francesco; Mazzarella, Giuseppe; Stefanile, Rosita; Rossi, Mauro

    2006-11-01

    Conjugated linoleic acid (CLA), a naturally occurring peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand, exhibits proapoptotic, immunomodulatory, and anticancer properties. In this study, we examined the biological effects of CLA administration in the MRL/MpJ-Fas(lpr) mouse, an animal model of systemic lupus erythematosus (SLE). We found that CLA exerted apparently opposed activities in in vitro experiments, depending on its concentration: 100 microM CLA downregulated IFN gamma synthesis and cell proliferation of splenocytes, in association with apoptosis induction and a decrease of intracellular thiols (GSH + GSSG), whereas 25 microM CLA did not significantly influence cell proliferation but enhanced the expression of gamma-glutamylcysteine ligase catalytic subunit (GCLC) and intracellular GSH concentration. Interestingly, the antiproliferative effect at 100 microM was not inhibited by the PPAR gamma antagonist GW9662. In vivo, CLA administration drastically reduced SLE signs (splenomegaly, autoantibodies, and cytokine synthesis), a condition paralleled by the enhancement of GCLC expression and intracellular GSH content. Moreover, CLA administration significantly downregulated nuclear factor kappaB activity independent of PPAR gamma activation and apoptosis induction. In conclusion, enhanced GSH content and GCLC expression in CLA-treated mice suggest a novel biochemical mechanism underlying its immunomodulatory activity and the beneficial effects on murine SLE signs.

  15. Shift in microbial group during remediation by enhanced natural attenuation (RENA) of a crude oil-impacted soil: a case study of Ikarama Community, Bayelsa, Nigeria.

    PubMed

    Chikere, Chioma Blaise; Azubuike, Christopher Chibueze; Fubara, Evan Miebaka

    2017-06-01

    Acute and chronic pollution of environments with crude oil does not bode well for biota living within the vicinity of polluted environments. This is due to environmental and public health concerns on the negative impact of crude oil pollution on living organisms. Enhancing microbial activities by adding nutrients and other amendments had proved effective in pollutant removal during bioremediation. This study was carried out to determine how microbial group respond during remediation by enhanced natural attenuation (RENA) during a field-scale bioremediation. Crude oil-polluted soil samples were collected (before, during, and after remediation) from a site undergoing remediation by enhanced natural attenuation (RENA) at Ikarama Community, Bayelsa State, Nigeria, and were analyzed for total petroleum hydrocarbon (TPH), polyaromatic hydrocarbon (PAH), and a shift in microbial community. The gas chromatography-flame ionization detector (GC-FID) results showed that the pollutant concentrations (TPH and PAH) reduced by 98 and 85%, respectively, after the remediation. Culturable hydrocarbon utilizing bacteria (CHUB) was highest (8.3 × 10(4) cfu/g) for sample collected during the remediation studies, whilst sample collected after remediation had low CHUB (6.1 × 10(4) cfu/g) compared to that collected before remediation (7.7 × 10(4) cfu/g). Analysis of 16S rRNA of the isolated CHUB showed they belonged to eight bacterial genera namely: Achromobacter, Alcaligenes, Azospirillus, Bacillus, Lysinibacillus, Ochrobactrum, Proteus, and Pusillimonas, with Alcaligenes as the dominant genus. In this study, it was observed that the bacterial community shifted from mixed group (Gram-positive and -negative) before and during the remediation, to only the latter group after the remediation studies. The betaproteobacteria groups were the dominant isolated bacterial phylotype. This study showed that RENA is an effective method of reducing pollutant concentration in crude oil

  16. Nanotechnology enabled enhancement of enzyme activity and thermostability: study on impaired pectate lyase from attenuated Macrophomina phaseolina in presence of hydroxyapatite nanoparticle.

    PubMed

    Dutta, Nalok; Mukhopadhyay, Arka; Dasgupta, Anjan Kr; Chakrabarti, Krishanu

    2013-01-01

    In this paper we show that hydroxyapatite nanoparticles (NP) can not only act as a chaperon (by imparting thermostability) but can serve as a synthetic enhancer of activity of an isolated extracellular pectate lyase (APL) with low native state activity. The purified enzyme (an attenuated strain of Macrophomina phaseolina) showed feeble activity at 50°C and pH 5.6. However, on addition of 10.5 µg/ml of hydroxyapatite nanoparticles (NP), APL activity increased 27.7 fold with a 51 fold increase in half-life at a temperature of 90°C as compared to untreated APL. The chaperon like activity of NP was evident from entropy-enthalpy compensation profile of APL. The upper critical temperature for such compensation was elevated from 50°C to 90°C in presence of NP. This dual role of NP in enhancing activity and conferring thermostability to a functionally impaired enzyme is reported for the first time.

  17. Nanotechnology Enabled Enhancement of Enzyme Activity and Thermostability: Study on Impaired Pectate Lyase from Attenuated Macrophomina phaseolina in Presence of Hydroxyapatite Nanoparticle

    PubMed Central

    Dutta, Nalok; Mukhopadhyay, Arka; Dasgupta, Anjan Kr.; Chakrabarti, Krishanu

    2013-01-01

    In this paper we show that hydroxyapatite nanoparticles (NP) can not only act as a chaperon (by imparting thermostability) but can serve as a synthetic enhancer of activity of an isolated extracellular pectate lyase (APL) with low native state activity. The purified enzyme (an attenuated strain of Macrophomina phaseolina) showed feeble activity at 50°C and pH 5.6. However, on addition of 10.5 µg/ml of hydroxyapatite nanoparticles (NP), APL activity increased 27.7 fold with a 51 fold increase in half-life at a temperature of 90°C as compared to untreated APL. The chaperon like activity of NP was evident from entropy–enthalpy compensation profile of APL. The upper critical temperature for such compensation was elevated from 50°C to 90°C in presence of NP. This dual role of NP in enhancing activity and conferring thermostability to a functionally impaired enzyme is reported for the first time. PMID:23691068

  18. Potential of fluid-attenuated inversion recovery MRI as an alternative to contrast-enhanced MRI for oral and maxillofacial vascular malformations: experimental and clinical studies.

    PubMed

    Sasaki, Yoshinori; Sakamoto, Junichiro; Otonari-Yamamoto, Mika; Nishikawa, Keiichi; Sano, Tsukasa

    2013-10-01

    To determine the potential of fluid-attenuated inversion recovery (FLAIR) imaging of oral and maxillofacial vascular malformations as an alternative to contrast-enhanced magnetic resonance imaging (MRI), we investigated the influence of differences in T1 and T2 values on image contrast in FLAIR images and evaluated the diagnostic utility of such images. FLAIR imaging and heavily T2-weighted (hT2-weighted) imaging were performed using a phantom. FLAIR and hT2-weighted images of 32 lesions (11 mucous cysts, 12 vascular malformations, and 9 tumors) were also studied retrospectively. The contrast-to-noise ratios (CNRs) and CNR change ratios were compared. All aqueous solutions except those with a short T2 value were discriminated by CNR change ratio (P < .05). All 3 types of lesions were discriminated by CNR change ratio (P < .05). FLAIR imaging has potential as an alternative to contrast-enhanced MRI in differentiating vascular malformations from other types of lesions in the oral and maxillofacial region. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Repeated administration of almonds increases brain acetylcholine levels and enhances memory function in healthy rats while attenuates memory deficits in animal model of amnesia.

    PubMed

    Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Tabassum, Saiqa; Madiha, Syeda; Rafiq, Sahar; Tariq, Sumayya; Batool, Tuba Sharf; Saleem, Sadia; Naqvi, Fizza; Perveen, Tahira; Haider, Saida

    2016-01-01

    Dietary nutrients may play a vital role in protecting the brain from age-related memory dysfunction and neurodegenerative diseases. Tree nuts including almonds have shown potential to combat age-associated brain dysfunction. These nuts are an important source of essential nutrients, such as tocopherol, folate, mono- and poly-unsaturated fatty acids, and polyphenols. These components have shown promise as possible dietary supplements to prevent or delay the onset of age-associated cognitive dysfunction. This study investigated possible protective potential of almond against scopolamine induced amnesia in rats. The present study also investigated a role of acetylcholine in almond induced memory enhancement. Rats in test group were orally administrated with almond suspension (400 mg/kg/day) for four weeks. Both control and almond-treated rats were then divided into saline and scopolamine injected groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM) and novel object recognition (NOR) task. Cholinergic function was determined in terms of hippocampal and frontal cortical acetylcholine content and acetylcholinesterase activity. Results of the present study suggest that almond administration for 28 days significantly improved memory retention. This memory enhancing effect of almond was also observed in scopolamine induced amnesia model. Present study also suggests a role of acetylcholine in the attenuation of scopolamine induced amnesia by almond. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Attenuated allergic airway hyperresponsiveness in C57BL/6 mice is associated with enhanced surfactant protein (SP)-D production following allergic sensitization

    PubMed Central

    Atochina, Elena N; Beers, Michael F; Tomer, Yaniv; Scanlon, Seth T; Russo, Scott J; Panettieri, Reynold A; Haczku, Angela

    2003-01-01

    Background C57BL/6 mice have attenuated allergic airway hyperresponsiveness (AHR) when compared with Balb/c mice but the underlying mechanisms remain unclear. SP-D, an innate immune molecule with potent immunosuppressive activities may have an important modulatory role in the allergic airway response and the consequent physiological changes. We hypothesized that an elevated SP-D production is associated with the impaired ability of C57BL/6 mice to develop allergic AHR. Methods SP-D mRNA and protein expression was investigated during development of allergic airway changes in a model of Aspergillus fumigatus (Af)-induced allergic inflammation. To study whether strain dependency of allergic AHR is associated with different levels of SP-D in the lung, Balb/c and C57BL/6 mice were compared. Results Sensitization and exposure to Af induced significant airway inflammation in both mouse strains in comparison with naïve controls. AHR to acetylcholine however was significantly attenuated in C57BL/6 mice in spite of increased eosinophilia and serum IgE when compared with Balb/c mice (p < 0.05). Af challenge of sensitized C57BL/6 mice induced a markedly increased SP-D protein expression in the SA surfactant fraction (1,894 ± 170% of naïve controls) that was 1.5 fold greater than the increase in Balb/c mice (1,234 ± 121% p < 0.01). These changes were selective since levels of the hydrophobic SP-B and SP-C and the hydrophilic SP-A were significantly decreased following sensitization and challenge with Af in both strains. Further, sensitized and exposed C57BL/6 mice had significantly lower IL-4 and IL-5 in the BAL fluid than that of Balb/c mice (p < 0.05). Conclusions These results suggest that enhanced SP-D production in the lung of C57BL/6 mice may contribute to an attenuated AHR in response to allergic airway sensitization. SP-D may act by inhibiting synthesis of Th2 cytokines. PMID:14748931

  1. Dimethyl fumarate attenuates 6-OHDA-induced neurotoxicity in SH-SY5Y cells and in animal model of Parkinson's disease by enhancing Nrf2 activity.

    PubMed

    Jing, X; Shi, H; Zhang, C; Ren, M; Han, M; Wei, X; Zhang, X; Lou, H

    2015-02-12

    Oxidative stress is central to the pathology of several neurodegenerative diseases, including Parkinson's disease (PD), and therapeutics designed to enhance antioxidant potential could have clinical value. In this study, we investigated whether dimethyl fumarate (DMF) has therapeutic effects in cellular and animal model of PD, and explore the role of nuclear transcription factor related to NF-E2 (Nrf2) in this process. Treatment of animals and dopaminergic SH-SY5Y cells with DMF resulted in increased nuclear levels of active Nrf2, with subsequent upregulation of antioxidant target genes. The cytotoxicity of 6-hydroxydopamine (6-OHDA) was reduced by pre-treatment with DMF in SH-SY5Y cells. The increase in the reactive oxygen species caused by 6-OHDA treatment was also attenuated by DMF in SH-SY5Y cells. The neuroprotective effects of DMF against 6-OHDA neurotoxicity were dependent on Nrf2, since treatment with Nrf2 siRNA failed to block against 6-OHDA neurotoxicity and induce Nrf2-dependent cytoprotective genes in SH-SY5Y cells. In vivo, DMF oral administration was shown to upregulate mRNA and protein levels of Nrf2 and Nrf2-regulated cytoprotective genes, attenuate 6-OHDA induced striatal oxidative stress and inflammation in C57BL/6 mice. Moreover, DMF ameliorated dopaminergic neurotoxicity in 6-OHDA-induced PD animal models as evidenced by amelioration of locomotor dysfunction, loss in striatal dopamine, and reductions in dopaminergic neurons in the substantia nigra and striatum. Taken together, these data strongly suggest that DMF may be beneficial for the treatment of neurodegenerative diseases like PD. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Gene-Category Analysis.

    PubMed

    Bauer, Sebastian

    2017-01-01

    Gene-category analysis is one important knowledge integration approach in biomedical sciences that combines knowledge bases such as Gene Ontology with lists of genes or their products, which are often the result of high-throughput experiments, gained from either wet-lab or synthetic experiments. In this chapter, we will motivate this class of analyses and describe an often used variant that is based on Fisher's exact test. We show that this approach has some problems in the context of Gene Ontology of which users should be aware. We then describe some more recent algorithms that try to address some of the shortcomings of the standard approach.

  3. Cilostazol attenuates ischemic brain injury and enhances neurogenesis in the subventricular zone of adult mice after transient focal cerebral ischemia.

    PubMed

    Tanaka, Y; Tanaka, R; Liu, M; Hattori, N; Urabe, T

    2010-12-29

    Evidence suggests that neurogenesis occurs in the adult mammalian brain, and that various stimuli, for example, ischemia/hypoxia, enhance the generation of neural progenitor cells in the subventricular zone (SVZ) and their migration into the olfactory bulb. In a mouse stroke model, focal ischemia results in activation of neural progenitor cells followed by their migration into the ischemic lesion. The present study assessed the in vivo effects of cilostazol, a type 3 phosphodiesterase inhibitor known to activate the cAMP-responsive element binding protein (CREB) signaling, on neurogenesis in the ipsilateral SVZ and peri-infarct area in a mouse model of transient middle cerebral artery occlusion. Mice were divided into sham operated (n=12), vehicle- (n=18) and cilostazol-treated (n=18) groups. Sections stained for 5-bromodeoxyuridine (BrdU) and several neuronal and a glial markers were analyzed at post-ischemia days 1, 3 and 7. Cilostazol reduced brain ischemic volume (P<0.05) and induced earlier recovery of neurologic deficit (P<0.05). Cilostazol significantly increased the density of BrdU-positive newly-formed cells in the SVZ compared with the vehicle group without ischemia. Increased density of doublecortin (DCX)-positive and BrdU/DCX-double positive neural progenitor cells was noted in the ipsilateral SVZ and peri-infarct area at 3 and 7 days after focal ischemia compared with the vehicle group (P<0.05). Cilostazol increased DCX-positive phosphorylated CREB (pCREB)-expressing neural progenitor cells, and increased brain derived neurotrophic factor (BDNF)-expressing astrocytes in the ipsilateral SVZ and peri-infarct area. The results indicated that cilostazol enhanced neural progenitor cell generation in both ipsilateral SVZ and peri-infarct area through CREB-mediated signaling pathway after focal ischemia.

  4. Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice

    SciTech Connect

    Chan, Ming-Huan; Chung, Shiang-Sheng; Stoker, Astrid K.; Markou, Athina; Chen, Hwei-Hsien

    2012-12-01

    Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-D-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDA receptor co-agonist and by inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure. -- Highlights: ► Toluene induces impairments in Rotarod test and novel object recognition test. ► Toluene lowers rectal temperature and ICSS thresholds in mice. ► Sarcosine reverses toluene-induced changes in motor, memory and body temperature. ► Sarcosine pretreatment does not affect toluene

  5. Delayed administration of the nucleic acid analog 2Cl-C.OXT-A attenuates brain damage and enhances functional recovery after ischemic stroke.

    PubMed

    Okabe, Naohiko; Nakamura, Emi; Himi, Naoyuki; Narita, Kazuhiko; Tsukamoto, Ikuko; Maruyama, Tokumi; Sakakibara, Norikazu; Nakamura, Takehiro; Itano, Toshifumi; Miyamoto, Osamu

    2013-04-19

    2Cl-C.OXT-A (COA-Cl) is a novel nucleic acid analog that enhances angiogenesis through extracellular signal-regulated kinase 1 or 2 (ERK1/2) activation. ERK1/2 is a well-known kinase that regulates cell survival, proliferation and differentiation in the central nervous system. We performed in vitro and in vivo experiments to investigate whether COA-Cl can attenuate neuronal damage and enhance recovery after brain ischemia. In primary cortical neuron cultures, COA-Cl prevented neuronal injury after 2h of oxygen-glucose deprivation. COA-Cl increased phospho-ERK levels in a dose-dependent manner and COA-Cl-induced neuroprotection and ERK1/2 activation was inhibited by suramin or PD98059. The effect of COA-Cl was evaluated in vivo with 60min of middle cerebral artery occlusion combined with bilateral common carotid artery occlusion. COA-Cl or saline was injected intracerebroventricularly 5min after reperfusion. COA-Cl significantly reduced infarct volume and improved neurological deficits upon injection of 15 or 30μg/kg COA-Cl. Moreover, COA-Cl reduced the number of TUNEL positive cells in ischemic boundary, while rCBF was not significantly changed by COA-Cl administration. We also evaluated the effect of delayed COA-Cl administration on recovery from brain ischemia by continuous administration of COA-Cl from 1 to 8 days after reperfusion. Delayed continuous COA-Cl administration also reduced infarct volume. Furthermore, COA-Cl enhanced peri-infarct angiogenesis and synaptogenesis, resulting in improved motor function recovery. Our findings demonstrate that COA-Cl exerts both neuroprotective and neurorestorative effects over a broad therapeutic time window, suggesting COA-Cl might be a novel and potent therapeutic agent for ischemic stroke.

  6. PPARγ Activation Attenuates Glycated-Serum Induced Pancreatic Beta-Cell Dysfunction through Enhancing Pdx1 and Mafa Protein Stability

    PubMed Central

    Zhu, Yunxia; Ma, Ai; Zhang, Hongxiu; Li, Chaojun

    2013-01-01

    Pancreatic-duodenal homeobox-1 (Pdx1) and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) play important roles in sustaining the pancreatic beta-cell differentiation phenotype. Peroxisome proliferator-activated receptor-γ (PPARγ) is also a regulator of cell differentiation. Our previous study revealed that glycated serum (GS) causes beta-cell dedifferentiation by down-regulating beta-cell specific genes, such as insulin and Pdx1. Here, we show that GS enhanced the cellular accumulation of ubiquitin-conjugated proteins, including Pdx1 and Mafa, in pancreatic beta-cells. Pharmacologic inhibition of proteolytic activity restored the protein levels of Pdx1 and Mafa, whereas inhibition of de novo protein synthesis accelerated their degradation. These findings suggest that both Pdx1 and Mafa are regulated at the post-transcriptional level. We further show that activation of PPARγ could restore GS-induced reduction of Pdx1 and Mafa protein levels, leading to improved insulin secretion and synthesis. Moreover, ectopic expression of Bcl-xl, a mitochondrial regulator, also restored Pdx1 and Mafa protein levels, linking mitochondrial function to Pdx1 and Mafa stability. Taken together, our results identify a key role of PPARγ in regulating pancreatic beta-cell function by improving the stability of Pdx1 and Mafa proteins. PMID:23424659

  7. Enhanced excitation-coupled calcium entry in myotubes expressing malignant hyperthermia mutation R163C is attenuated by dantrolene.

    PubMed

    Cherednichenko, Gennady; Ward, Chris W; Feng, Wei; Cabrales, Elaine; Michaelson, Luke; Samso, Montserrat; López, José R; Allen, Paul D; Pessah, Isaac N

    2008-04-01

    Dantrolene is the drug of choice for the treatment of malignant hyperthermia (MH) and is also useful for treatment of spasticity or muscle spasms associated with several clinical conditions. The current study examines the mechanisms of dantrolene's action on skeletal muscle and shows that one of dantrolene's mechanisms of action is to block excitation-coupled calcium entry (ECCE) in both adult mouse flexor digitorum brevis fibers and primary myotubes. A second important new finding is that myotubes isolated from mice heterozygous and homozygous for the ryanodine receptor type 1 R163C MH susceptibility mutation show significantly enhanced ECCE rates that could be restored to those measured in wild-type cells after exposure to clinical concentrations of dantrolene. We propose that this gain of ECCE function is an important etiological component of MH susceptibility and possibly contributes to the fulminant MH episode. The inhibitory potency of dantrolene on ECCE found in wild-type and MH-susceptible muscle is consistent with the drug's clinical potency for reversing the MH syndrome and is incomplete as predicted by its efficacy as a muscle relaxant.

  8. Enhanced Excitation-Coupled Calcium Entry in Myotubes Expressing Malignant Hyperthermia Mutation R163C Is Attenuated by Dantrolene

    PubMed Central

    Cherednichenko, Gennady; Ward, Chris W.; Feng, Wei; Cabrales, Elaine; Michaelson, Luke; Samso, Montserrat; López, José R.; Allen, Paul D.; Pessah, Isaac N.

    2009-01-01

    Dantrolene is the drug of choice for the treatment of malignant hyperthermia (MH) and is also useful for treatment of spasticity or muscle spasms associated with several clinical conditions. The current study examines the mechanisms of dantrolene's action on skeletal muscle and shows that one of dantrolene's mechanisms of action is to block excitation-coupled calcium entry (ECCE) in both adult mouse flexor digitorum brevis fibers and primary myotubes. A second important new finding is that myotubes isolated from mice heterozygous and homozygous for the ryanodine receptor type 1 R163C MH susceptibility mutation show significantly enhanced ECCE rates that could be restored to those measured in wild-type cells after exposure to clinical concentrations of dantrolene. We propose that this gain of ECCE function is an important etiological component of MH susceptibility and possibly contributes to the fulminant MH episode. The inhibitory potency of dantrolene on ECCE found in wild-type and MH-susceptible muscle is consistent with the drug's clinical potency for reversing the MH syndrome and is incomplete as predicted by its efficacy as a muscle relaxant. PMID:18171728

  9. Modelling of an enhanced PAH attenuation experiment and associated biogeochemical changes at a former gasworks site in southern Germany

    NASA Astrophysics Data System (ADS)

    Herold, Maria; Greskowiak, Janek; Ptak, Thomas; Prommer, Henning

    2011-01-01

    Former manufactured gas plant sites often form a widespread contaminant source in the subsurface, leading to large plumes that contain a wide variety of tar-oil related compounds. Although most of these compounds eventually degrade naturally, the relevant processes tend to be slow and inefficient, often leaving active remediation as the only viable option to eliminate the risks of toxic substances to reach potential receptors such as surface waters or drinking water wells. In this study we use a reactive transport model to analyse the fate of a contaminant plume containing acenaphthene, methylbenzofurans and dimethylbenzofurans (i) prior to the installation of an active remediation scheme and (ii) for an enhanced remediation experiment during which O 2 and H 2O 2 were added to the contaminated groundwater through a recirculation well. The numerical model developed for this study considers the primary contaminant degradation reactions (i.e., microbially mediated redox reactions) as well as secondary and competing mineral precipitation/dissolution reactions that affect the site's hydrochemistry and/or contaminant fate. The model was calibrated using a variety of constraints to test the uncertainty on model predictions resulting from the undocumented presence of reductants such as pyrite. The results highlight the important role of reactive transport modelling for the development of a comprehensive process understanding.

  10. Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice

    PubMed Central

    Chan, Ming-Huan; Chung, Shiang-Sheng; Stoker, Astrid K; Markou, Athina; Chen, Hwei-Hsien

    2012-01-01

    Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-d-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDA receptor co-agonist and inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure. PMID:23067721

  11. Resveratrol Co-Treatment Attenuates the Effects of HIV Protease Inhibitors on Rat Body Weight and Enhances Cardiac Mitochondrial Respiration

    PubMed Central

    Symington, Burger; Mapanga, Rudo F.; Norton, Gavin R.

    2017-01-01

    Since the early 1990s human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) emerged as a global health pandemic, with sub-Saharan Africa the hardest hit. While the successful roll-out of antiretroviral (ARV) therapy provided significant relief to HIV-positive individuals, such treatment can also elicit damaging side-effects. Here especially HIV protease inhibitors (PIs) are implicated in the onset of cardio-metabolic complications such as type-2 diabetes and coronary heart disease. As there is a paucity of data regarding suitable co-treatments within this context, this preclinical study investigated whether resveratrol (RSV), aspirin (ASP) or vitamin C (VitC) co-treatment is able to blunt side-effects in a rat model of chronic PI exposure (Lopinavir/Ritonavir treatment for 4 months). Body weights and weight gain, blood metabolite levels (total cholesterol, HDL, LDL, triglycerides), echocardiography and cardiac mitochondrial respiration were assessed in PI-treated rats ± various co-treatments. Our data reveal that PI treatment significantly lowered body weight and cardiac respiratory function while no significant changes were found for heart function and blood metabolite levels. Moreover, all co-treatments ameliorated the PI-induced decrease in body weight after 4 months of PI treatment, while RSV co-treatment enhanced cardiac mitochondrial respiratory capacity in PI-treated rats. This pilot study therefore provides novel hypotheses regarding RSV co-treatment that should be further assessed in greater detail. PMID:28107484

  12. Radiofrequency attenuator and method

    DOEpatents

    Warner, Benjamin P.; McCleskey, T. Mark; Burrell, Anthony K.; Agrawal, Anoop; Hall, Simon B.

    2009-11-10

    Radiofrequency attenuator and method. The attenuator includes a pair of transparent windows. A chamber between the windows is filled with molten salt. Preferred molten salts include quarternary ammonium cations and fluorine-containing anions such as tetrafluoroborate (BF.sub.4.sup.-), hexafluorophosphate (PF.sub.6.sup.-), hexafluoroarsenate (AsF.sub.6.sup.-), trifluoromethylsulfonate (CF.sub.3SO.sub.3.sup.-), bis(trifluoromethylsulfonyl)imide ((CF.sub.3SO.sub.2).sub.2N.sup.-), bis(perfluoroethylsulfonyl)imide ((CF.sub.3CF.sub.2SO.sub.2).sub.2N.sup.-) and tris(trifluoromethylsulfonyl)methide ((CF.sub.3SO.sub.2).sub.3 C.sup.-). Radicals or radical cations may be added to or electrochemically generated in the molten salt to enhance the RF attenuation.

  13. Radiofrequency attenuator and method

    DOEpatents

    Warner, Benjamin P [Los Alamos, NM; McCleskey, T Mark [Los Alamos, NM; Burrell, Anthony K [Los Alamos, NM; Agrawal, Anoop [Tucson, AZ; Hall, Simon B [Palmerston North, NZ

    2009-01-20

    Radiofrequency attenuator and method. The attenuator includes a pair of transparent windows. A chamber between the windows is filled with molten salt. Preferred molten salts include quarternary ammonium cations and fluorine-containing anions such as tetrafluoroborate (BF.sub.4.sup.-), hexafluorophosphate (PF.sub.6.sup.-), hexafluoroarsenate (AsF.sub.6.sup.-), trifluoromethylsulfonate (CF.sub.3SO.sub.3.sup.-), bis(trifluoromethylsulfonyl)imide ((CF.sub.3SO.sub.2).sub.2N.sup.-), bis(perfluoroethylsulfonyl)imide ((CF.sub.3CF.sub.2SO.sub.2).sub.2N.sup.-) and tris(trifluoromethylsulfonyl)methide ((CF.sub.3SO.sub.2).sub.3C.sup.-). Radicals or radical cations may be added to or electrochemically generated in the molten salt to enhance the RF attenuation.

  14. Enhanced expression of Nrf2 in mice attenuates the fatty liver produced by a methionine- and choline-deficient diet

    SciTech Connect

    Zhang, Yu-Kun Jennifer; Yeager, Ronnie L.; Tanaka, Yuji; Klaassen, Curtis D.

    2010-06-15

    Oxidative stress has been proposed as an important promoter of the progression of fatty liver diseases. The current study investigates the potential functions of the Nrf2-Keap1 signaling pathway, an important hepatic oxidative stress sensor, in a rodent fatty liver model. Mice with no (Nrf2-null), normal (wild type, WT), and enhanced (Keap1 knockdown, K1-kd) expression of Nrf2 were fed a methionine- and choline-deficient (MCD) diet or a control diet for 5 days. Compared to WT mice, the MCD diet-caused hepatosteatosis was more severe in the Nrf2-null mice and less in the K1-kd mice. The Nrf2-null mice had lower hepatic glutathione and exhibited more lipid peroxidation, whereas the K1-kd mice had the highest amount of glutathione in the liver and developed the least lipid peroxidation among the three genotypes fed the MCD diet. The Nrf2 signaling pathway was activated by the MCD diet, and the Nrf2-targeted cytoprotective genes Nqo1 and Gst{alpha}1/2 were induced in WT and even more in K1-kd mice. In addition, Nrf2-null mice on both control and MCD diets exhibited altered expression profiles of fatty acid metabolism genes, indicating Nrf2 may influence lipid metabolism in liver. For example, mRNA levels of long chain fatty acid translocase CD36 and the endocrine hormone Fgf21 were higher in livers of Nrf2-null mice and lower in the K1-kd mice than WT mice fed the MCD diet. Taken together, these observations indicate that Nrf2 could decelerate the onset of fatty livers caused by the MCD diet by increasing hepatic antioxidant and detoxification capabilities.

  15. α-TLR2 antibody attenuates the Aβ-mediated inflammatory response in microglia through enhanced expression of SIGIRR.

    PubMed

    Costello, Derek A; Carney, Dónal G; Lynch, Marina A

    2015-05-01

    The immunoregulatory function of single-Ig-interleukin-1 related receptor (SIGIRR) is derived from its ability to constrain the inflammatory consequences of interleukin (IL)-1R and toll-like receptor (TLR)4 activation. This role extends to the brain, where SIGIRR deficiency increases the synaptic and cognitive dysfunction associated with IL-1R- and TLR4-mediated signalling. The current study set out to investigate the interaction between SIGIRR and TLR2 in brain tissue and the data demonstrate that the response to the TLR2 agonist, Pam3CysSK4 (Pam3Cys4), is enhanced in glial cells from SIGIRR(-/-) animals. Consistent with the view that β-amyloid peptide (Aβ) signals through activation of TLR2, the data also show that Aβ-induced changes are exaggerated in glia from SIGIRR(-/-) animals. We report that microglia, rather than astrocytes, are the primary glial cell expressing both TLR2 and SIGIRR. While Aβ increased TLR2 expression, it decreased SIGIRR expression in microglia. This was mimicked by direct activation of TLR2 with Pam3Cys4. We investigated the effect of an anti-TLR2 antibody (αTLR2) on the Aβ-induced inflammatory responses and demonstrate that it prevented the expression and release of the pro-inflammatory cytokines TNFα and IL-6 from microglia. In addition, application of αTLR2 alleviated the Aβ-mediated impairment in long-term potentiation (LTP) of hippocampal synaptic activity. The protective effects of αTLR2 were accompanied by an up-regulation in SIGIRR expression. We propose that a mechanism involving activation of PI3 kinase/Akt and the transcription factor peroxisome proliferator-activated receptor (PPAR)γ may facilitate this increase in SIGIRR. These findings highlight a novel role of SIGIRR as a negative regulator of TLR2-mediated inflammation in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Jordan Algebraic Quantum Categories

    NASA Astrophysics Data System (ADS)

    Graydon, Matthew; Barnum, Howard; Ududec, Cozmin; Wilce, Alexander

    2015-03-01

    State cones in orthodox quantum theory over finite dimensional complex Hilbert spaces enjoy two particularly essential features: homogeneity and self-duality. Orthodox quantum theory is not, however, unique in that regard. Indeed, all finite dimensional formally real Jordan algebras -- arenas for generalized quantum theories with close algebraic kinship to the orthodox theory -- admit homogeneous self-dual positive cones. We construct categories wherein these theories are unified. The structure of composite systems is cast from universal tensor products of the universal C*-algebras enveloping ambient spaces for the constituent state cones. We develop, in particular, a notion of composition that preserves the local distinction of constituent systems in quaternionic quantum theory. More generally, we explicitly derive the structure of hybrid quantum composites with subsystems of arbitrary Jordan algebraic type.

  17. Beyond the Categories.

    PubMed

    Weeks, Jeffrey

    2015-07-01

    Shushu is a Turkish Cypriot drag performance artist and the article begins with a discussion of a short film about him by a Greek Cypriot playwright, film maker, and gay activist. The film is interesting in its own right as a documentary about a complex personality, but it is also relevant to wider discussion of sexual and gender identity and categorization in a country divided by history, religion, politics, and military occupation. Shushu rejects easy identification as gay or transgender, or anything else. He is his own self. But refusing a recognized and recognizable identity brings problems, and I detected a pervasive mood of melancholy in his portrayal. The article builds from this starting point to explore the problematic nature of identities and categorizations in the contemporary world. The analysis opens with the power of words and language in defining and classifying sexuality. The early sexologists set in motion a whole catalogue of categories which continue to shape sexual thinking, believing that they were providing a scientific basis for a more humane treatment of sexual variations. This logic continues in DSM-5. The historical effect, however, has been more complex. Categorizations have often fixed individuals into a narrow band of definitions and identities that marginalize and pathologize. The emergence of radical sexual-social movements from the late 1960s offered new forms of grassroots knowledge in opposition to the sexological tradition, but at first these movements worked to affirm rather than challenge the significance of identity categories. Increasingly, however, identities have been problematized and challenged for limiting sexual and gender possibilities, leading to the apparently paradoxical situation where sexual identities are seen as both necessary and impossible. There are emotional costs both in affirming a fixed identity and in rejecting one. Shushu is caught in this dilemma, leading to the pervasive sense of loss that shapes the

  18. Mesenchymal stem cells attenuate hydrogen peroxide-induced oxidative stress and enhance neuroprotective effects in retinal ganglion cells.

    PubMed

    Cui, Yi; Xu, Nuo; Xu, Wei; Xu, Guoxing

    2017-04-01

    The apoptosis of retinal ganglion cells leads to visual impairment and blindness in ocular neurodegenerative diseases, especially in diabetic retinopathy (DR). Mounting evidence suggests that oxidative stress contributes to the pathogenesis of DR. In the present study, we investigated whether bone mesenchymal stem cells (BMSCs) have protective ability to relieve hydrogen peroxide (H2O2)-induced injury on retinal ganglion cells in vitro. An immortalized retinal ganglion cells, RGC-5 cells, were exposed to an indicated concentration of H2O2 for 24 h. Cell viability was analyzed by CCK-8 assay to find out a certain concentration to build H2O2 oxidative damage model. Morphological changes in RGC-5 cells were observed under optical microscope, and cell apoptosis was detected with Hoechst fluorescence staining. Then, BMSCs were co-cultured with RGC-5 cells in a transwell culture system for 24 h and 48 h. Flow cytometry was performed to qualify the apoptosis rate of RGC-5 cells. Conditioned medium was collected for evaluation the inflammatory cytokines by ELISA. The content of intracellular malondialdehyde (MDA) and superoxide dismutase (SOD) was assayed by thiobarbituric acid and xanthine oxidase method, respectively. qRT-PCR and ELISA were conducted for analysis of the expression changes in brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), respectively. After H2O2 exposure, the morphological varieties were observed as cytoplasm shrinking and paramorphia together with nuclear gathering. Meanwhile, the apoptotic cells had hyperfluorescence with Hoechst 33258 staining. Co-culture with BMSCs significantly inhibited retinal cell death. It was found that BMSCs reduced H2O2-induced inflammatory factors IL-1β and TNF-α, down-regulated intracellular oxidant factor MDA, up-regulated intracellular antioxidant factor SOD, and increased neurotrophins BDNF and CNTF expression. BMSCs may enhance protective effect of RGC-5 cells in H2O2-induced

  19. Category Coherence and Category-Based Property Induction

    ERIC Educational Resources Information Center

    Rehder, Bob; Hastie, Reid

    2004-01-01

    One important property of human object categories is that they define the sets of exemplars to which newly observed properties are generalized. We manipulated the causal knowledge associated with novel categories and assessed the resulting strength of property inductions. We found that the theoretical coherence afforded to a category by…

  20. Category Coherence and Category-Based Property Induction

    ERIC Educational Resources Information Center

    Rehder, Bob; Hastie, Reid

    2004-01-01

    One important property of human object categories is that they define the sets of exemplars to which newly observed properties are generalized. We manipulated the causal knowledge associated with novel categories and assessed the resulting strength of property inductions. We found that the theoretical coherence afforded to a category by…

  1. Tonicity-responsive enhancer binding protein haplodeficiency attenuates seizure severity and NF-κB-mediated neuroinflammation in kainic acid-induced seizures

    PubMed Central

    Shin, H J; Kim, H; Heo, R W; Kim, H J; Choi, W S; Kwon, H M; Roh, G S

    2014-01-01

    Kainic acid (KA)-induced seizures followed by neuronal death are associated with neuroinflammation and blood–brain barrier (BBB) leakage. Tonicity-responsive enhancer binding protein (TonEBP) is known as a transcriptional factor activating osmoprotective genes, and in brain, it is expressed in neuronal nuclei. Thus dysregulation of TonEBP may be involved in the pathology of KA-induced seizures. Here we used TonEBP heterozygote (+/−) mice to study the roles of TonEBP. Electroencephalographic study showed that TonEBP (+/−) mice reduced seizure frequency and severity compared with wild type during KA-induced status epilepticus. Immunohistochemistry and western blotting analysis showed that KA-induced neuroinflammation and BBB leakage were dramatically reduced in TonEBP (+/−) mice. Similarly, TonEBP-specific siRNA reduced glutamate-induced death in HT22 hippocampal neuronal cells. TonEBP haplodeficiency prevented KA-induced nuclear translocation of NF-κB p65 and attenuated inflammation. Our findings identify TonEBP as a critical regulator of neuroinflammation and BBB leakage in KA-induced seizures, which suggests TonEBP as a good therapeutic target. PMID:24608792

  2. Attenuation by genistein of sodium-chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

    PubMed

    Tatsuta, M; Iishi, H; Baba, M; Yano, H; Uehara, H; Nakaizumi, A

    1999-01-29

    The effects of prolonged administration of genistein, a tyrosine-kinase inhibitor, on sodium-chloride-enhanced induction of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, and the labeling and apoptotic indices and vessel counts in the gastric mucosa and gastric cancers, were investigated in Wistar rats. After 25 weeks of the carcinogen treatment, rats were fed chow pellets containing 10% sodium chloride and were given s.c. injections of genistein at dosages of 15 mg/kg or 30 mg/kg body weight every other day. In week 52, the incidence of gastric cancers was significantly greater in rats fed sodium chloride than in untreated control rats. Prolonged administration of genistein at a dosage of 30 mg/kg, but not 15 mg/kg, body weight significantly reduced the incidence of gastric cancers, which was increased by oral treatment with sodium chloride. Genistein at the higher dose significantly decreased the labeling index and vessel counts of the antral mucosa and the gastric cancers (which were increased by treatment with sodium chloride) and significantly increased the apoptotic index of the antral mucosa and the cancers (which was lowered by the treatment with sodium chloride). These findings suggest that genistein attenuates gastric carcinogenesis promoted by sodium chloride, by inducing increased apoptosis and lower cell proliferation and angiogenesis of antral mucosa and gastric cancers.

  3. Tonicity-responsive enhancer binding protein haplodeficiency attenuates seizure severity and NF-κB-mediated neuroinflammation in kainic acid-induced seizures.

    PubMed

    Shin, H J; Kim, H; Heo, R W; Kim, H J; Choi, W S; Kwon, H M; Roh, G S

    2014-07-01

    Kainic acid (KA)-induced seizures followed by neuronal death are associated with neuroinflammation and blood-brain barrier (BBB) leakage. Tonicity-responsive enhancer binding protein (TonEBP) is known as a transcriptional factor activating osmoprotective genes, and in brain, it is expressed in neuronal nuclei. Thus dysregulation of TonEBP may be involved in the pathology of KA-induced seizures. Here we used TonEBP heterozygote (+/-) mice to study the roles of TonEBP. Electroencephalographic study showed that TonEBP (+/-) mice reduced seizure frequency and severity compared with wild type during KA-induced status epilepticus. Immunohistochemistry and western blotting analysis showed that KA-induced neuroinflammation and BBB leakage were dramatically reduced in TonEBP (+/-) mice. Similarly, TonEBP-specific siRNA reduced glutamate-induced death in HT22 hippocampal neuronal cells. TonEBP haplodeficiency prevented KA-induced nuclear translocation of NF-κB p65 and attenuated inflammation. Our findings identify TonEBP as a critical regulator of neuroinflammation and BBB leakage in KA-induced seizures, which suggests TonEBP as a good therapeutic target.

  4. Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages.

    PubMed

    Ran, Lin; Yu, Qilin; Zhang, Shu; Xiong, Fei; Cheng, Jia; Yang, Ping; Xu, Jun-Fa; Nie, Hao; Zhong, Qin; Yang, Xueli; Yang, Fei; Gong, Quan; Kuczma, Michal; Kraj, Piotr; Gu, Weikuan; Ren, Bo-Xu; Wang, Cong-Yi

    2015-07-01

    Acute schistosomiasis is characterized by pro-inflammatory responses against tissue- or organ-trapped parasite eggs along with granuloma formation. Here, we describe studies in Cx3cr1(-/-) mice and demonstrate the role of Cx3cr1 in the pathoetiology of granuloma formation during acute schistosomiasis. Mice deficient in Cx3cr1 were protected from granuloma formation and hepatic injury induced by Schistosoma japonicum eggs, as manifested by reduced body weight loss and attenuated hepatomegaly along with preserved liver function. Notably, S. japonicum infection induced high levels of hepatic Cx3cr1 expression, which was predominantly expressed by infiltrating macrophages. Loss of Cx3cr1 rendered macrophages preferentially towards M2 polarization, which then led to a characteristic switch of the host immune defense from a conventional Th1 to a typical Th2 response during acute schistosomiasis. This immune switch caused by Cx3cr1 deficiency was probably associated with enhanced STAT6/PPAR-γ signaling and increased expression of indoleamine 2,3-dioxygenase (IDO), an enzyme that promotes M2 polarization of macrophages. Taken together, our data provide evidence suggesting that CX3CR1 could be a viable therapeutic target for treatment of acute schistosomiasis.

  5. Repeated dosing of ABT-102, a potent and selective TRPV1 antagonist, enhances TRPV1-mediated analgesic activity in rodents, but attenuates antagonist-induced hyperthermia.

    PubMed

    Honore, Prisca; Chandran, Prasant; Hernandez, Gricelda; Gauvin, Donna M; Mikusa, Joseph P; Zhong, Chengmin; Joshi, Shailen K; Ghilardi, Joseph R; Sevcik, Molly A; Fryer, Ryan M; Segreti, Jason A; Banfor, Patricia N; Marsh, Kennan; Neelands, Torben; Bayburt, Erol; Daanen, Jerome F; Gomtsyan, Arthur; Lee, Chih-Hung; Kort, Michael E; Reilly, Regina M; Surowy, Carol S; Kym, Philip R; Mantyh, Patrick W; Sullivan, James P; Jarvis, Michael F; Faltynek, Connie R

    2009-03-01

    Transient receptor potential vanilloid type 1 (TRPV1) is a ligand-gated ion channel that functions as an integrator of multiple pain stimuli including heat, acid, capsaicin and a variety of putative endogenous lipid ligands. TRPV1 antagonists have been shown to decrease inflammatory pain in animal models and to produce limited hyperthermia at analgesic doses. Here, we report that ABT-102, which is a potent and selective TRPV1 antagonist, is effective in blocking nociception in rodent models of inflammatory, post-operative, osteoarthritic, and bone cancer pain. ABT-102 decreased both spontaneous pain behaviors and those evoked by thermal and mechanical stimuli in these models. Moreover, we have found that repeated administration of ABT-102 for 5-12 days increased its analgesic activity in models of post-operative, osteoarthritic, and bone cancer pain without an associated accumulation of ABT-102 concentration in plasma or brain. Similar effects were also observed with a structurally distinct TRPV1 antagonist, A-993610. Although a single dose of ABT-102 produced a self-limiting increase in core body temperature that remained in the normal range, the hyperthermic effects of ABT-102 effectively tolerated following twice-daily dosing for 2 days. Therefore, the present data demonstrate that, following repeated administration, the analgesic activity of TRPV1 receptor antagonists is enhanced, while the associated hyperthermic effects are attenuated. The analgesic efficacy of ABT-102 supports its advancement into clinical studies.

  6. In Vitro Passage Selects for Chlamydia muridarum with Enhanced Infectivity in Cultured Cells but Attenuated Pathogenicity in Mouse Upper Genital Tract

    PubMed Central

    Chen, Chaoqun; Zhou, Zhou; Conrad, Turner; Yang, Zhangsheng; Dai, Jin; Li, Zhongyu

    2015-01-01

    Although modern Chlamydia muridarum has been passaged for decades, there are no reports on the consequences of serial passage with strong selection pressure on its fitness. In order to explore the potential for Pasteurian selection to induce genomic and phenotypic perturbations to C. muridarum, a starter population was passaged in cultured cells for 28 generations without standard infection assistance. The resultant population, designated CMG28, displays markedly reduced in vitro dependence on centrifugation for infection and low incidence and severity of upper genital tract pathology following intravaginal inoculation into mice compared to the parental C. muridarum population, CMG0. Deep sequencing of CMG0 and CMG28 revealed novel protein variants in the hypothetical genes TC0237 (Q117E) and TC0668 (G322R). In vitro attachment assays of isogenic plaque clone pairs with mutations in either TC0237 and TC0668 or only TC0237 reveal that TC0237(Q117E) is solely responsible for enhanced adherence to host cells. Paradoxically, double mutants, but not TC0237(Q117E) single mutants, display severely attenuated in vivo pathogenicity. These findings implicate TC0237 and TC0668 as novel genetic factors involved in chlamydial attachment and pathogenicity, respectively, and show that serial passage under selection pressure remains an effective tool for studying Chlamydia pathogenicity. PMID:25712926

  7. Four Weeks of Supplementation With Isolated Soy Protein Attenuates Exercise-Induced Muscle Damage and Enhances Muscle Recovery in Well Trained Athletes: A Randomized Trial

    PubMed Central

    Shenoy, Shweta; Dhawan, Mrinal; Singh Sandhu, Jaspal

    2016-01-01

    Background The effects of consumption of isolated soy protein (ISP) for a chronic period (4 weeks) on exercise induced muscle damage (EIMD) in athletic population have never been explored. Objectives To examine the effects of ISP on muscle damage indices elicited via a bout of damaging exercise. Patients and Methods Forty males (20 boxers, 20 cyclists) aged 18 - 28 years were randomly assigned to two groups (ISP and Placebo) (n = 20). All participants who engaged themselves in specific, regular training of 30 hours a week during the competitive season were included in the study. Participants consumed the supplement and the placebo for 4 weeks. The damaging exercise consisted of 100 consecutive drop-jumps. Pre and post supplementation readings of the criterion variables, highly sensitive C reactive protein (hs-cRP), creatine Kinase (CK), myeloperoxidase (MPO), isometric muscle strength, maximum aerobic capacity (VO2 max), heart rate (HR) and muscle soreness were obtained at baseline (Day 1), at 24 hours (Day 2) and at 48 hours (Day 3) following EIMD. Results Differences were observed in pre and post supplementation values (P < 0.05) indicating the effectiveness of soy protein in attenuating muscle damage and enhancing muscle recovery. Conclusions Our findings suggest that soy protein; a vegetable based supplement is effective, in ameliorating the negative effects of EIMD in trained athletic population. PMID:27826398

  8. Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages

    PubMed Central

    Ran, Lin; Yu, Qilin; Zhang, Shu; Xiong, Fei; Cheng, Jia; Yang, Ping; Xu, Jun-Fa; Nie, Hao; Zhong, Qin; Yang, Xueli; Yang, Fei; Gong, Quan; Kuczma, Michal; Kraj, Piotr; Gu, Weikuan; Ren, Bo-Xu; Wang, Cong-Yi

    2015-01-01

    ABSTRACT Acute schistosomiasis is characterized by pro-inflammatory responses against tissue- or organ-trapped parasite eggs along with granuloma formation. Here, we describe studies in Cx3cr1−/− mice and demonstrate the role of Cx3cr1 in the pathoetiology of granuloma formation during acute schistosomiasis. Mice deficient in Cx3cr1 were protected from granuloma formation and hepatic injury induced by Schistosoma japonicum eggs, as manifested by reduced body weight loss and attenuated hepatomegaly along with preserved liver function. Notably, S. japonicum infection induced high levels of hepatic Cx3cr1 expression, which was predominantly expressed by infiltrating macrophages. Loss of Cx3cr1 rendered macrophages preferentially towards M2 polarization, which then led to a characteristic switch of the host immune defense from a conventional Th1 to a typical Th2 response during acute schistosomiasis. This immune switch caused by Cx3cr1 deficiency was probably associated with enhanced STAT6/PPAR-γ signaling and increased expression of indoleamine 2,3-dioxygenase (IDO), an enzyme that promotes M2 polarization of macrophages. Taken together, our data provide evidence suggesting that CX3CR1 could be a viable therapeutic target for treatment of acute schistosomiasis. PMID:26035381

  9. Granulocyte-Colony Stimulating Factor (G-CSF) Accelerates Wound Healing in Hemorrhagic Shock Rats by Enhancing Angiogenesis and Attenuating Apoptosis

    PubMed Central

    Huang, Hong; Zhang, Qi; Liu, Jiejie; Hao, Haojie; Jiang, Chaoguang; Han, Weidong

    2017-01-01

    Background Following severe trauma, treatment of cutaneous injuries is often delayed by inadequate blood supply. The aim of the present study was to determine whether granulocyte-colony stimulating factor (G-CSF) protects endothelial cells (ECs) and enhances angiogenesis in a rat model of hemorrhagic shock (HS) combined with cutaneous injury after resuscitation. Material/Methods The HS rats with full-thickness defects were resuscitated and randomly divided into a G-CSF group (200 μg/kg body weight), a normal saline group, and a blank control group. Histological staining was to used estimate the recovery and apoptosis of skin. Apoptosis- and angiogenesis-related factors were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot (WB). Scratch assay, tube formation, and WB experiments were performed to verify the functional effects of G-CSF on HUVECs in vitro. Results H&E staining and Masson trichrome staining showed earlier inflammation resolution and collagen synthesis in the G-CSF-treated group. Angiogenesis-related factors were elevated at mRNA and protein levels. TUNEL staining suggested fewer apoptotic cells in the G-CSF group. The apoptotic-related factors were down-regulated and anti-apoptotic factors were up-regulated in the G-CSF-treated group. Scratch assay and tube formation experiments revealed that G-CSF facilitated migration ability and angiogenic potential of HUVECs. The angiogenic and anti-apoptotic effects were also enhanced in vitro. Conclusions Our results suggest that G-CSF after resuscitation attenuates local apoptosis and accelerates angiogenesis. These findings hold great promise for improving therapy for cutaneous injury in severe trauma and ischemia diseases. PMID:28559534

  10. Dietary Prebiotics and Bioactive Milk Fractions Improve NREM Sleep, Enhance REM Sleep Rebound and Attenuate the Stress-Induced Decrease in Diurnal Temperature and Gut Microbial Alpha Diversity

    PubMed Central

    Thompson, Robert S.; Roller, Rachel; Mika, Agnieszka; Greenwood, Benjamin N.; Knight, Rob; Chichlowski, Maciej; Berg, Brian M.; Fleshner, Monika

    2017-01-01

    Severe, repeated or chronic stress produces negative health outcomes including disruptions of the sleep/wake cycle and gut microbial dysbiosis. Diets rich in prebiotics and glycoproteins impact the gut microbiota and may increase gut microbial species that reduce the impact of stress. This experiment tested the hypothesis that consumption of dietary prebiotics, lactoferrin (Lf) and milk fat globule membrane (MFGM) will reduce the negative physiological impacts of stress. Male F344 rats, postnatal day (PND) 24, received a diet with prebiotics, Lf and MFGM (test) or a calorically matched control diet. Fecal samples were collected on PND 35/70/91 for 16S rRNA sequencing to examine microbial composition and, in a subset of rats; Lactobacillus rhamnosus was measured using selective culture. On PND 59, biotelemetry devices were implanted to record sleep/wake electroencephalographic (EEG). Rats were exposed to an acute stressor (100, 1.5 mA, tail shocks) on PND 87 and recordings continued until PND 94. Test diet, compared to control diet, increased fecal Lactobacillus rhamnosus colony forming units (CFU), facilitated non-rapid eye movement (NREM) sleep consolidation (PND 71/72) and enhanced rapid eye movement (REM) sleep rebound after stressor exposure (PND 87). Rats fed control diet had stress-induced reductions in alpha diversity and diurnal amplitude of temperature, which were attenuated by the test diet (PND 91). Stepwise multiple regression analysis revealed a significant linear relationship between early-life Deferribacteres (PND 35) and longer NREM sleep episodes (PND 71/72). A diet containing prebiotics, Lf and MFGM enhanced sleep quality, which was related to changes in gut bacteria and modulated the impact of stress on sleep, diurnal rhythms and the gut microbiota. PMID:28119579

  11. Conservation Level and Category Clustering

    ERIC Educational Resources Information Center

    Haynes, C. Rayfield; Kulhavy, Raymond W.

    1976-01-01

    Two experiments were conducted to test the hypothesis that category recall is related to the quantity conservation of mass, weight, and volume. The predicted association between conservation level and category recall was observed. (JMB)

  12. Conservation Level and Category Clustering

    ERIC Educational Resources Information Center

    Haynes, C. Rayfield; Kulhavy, Raymond W.

    1976-01-01

    Two experiments were conducted to test the hypothesis that category recall is related to the quantity conservation of mass, weight, and volume. The predicted association between conservation level and category recall was observed. (JMB)

  13. THE SCENARIOS APPROACH TO ATTENUATION-BASED REMEDIES FOR INORGANIC AND RADIONUCLIDE CONTAMINANTS

    SciTech Connect

    Vangelas, K.; Rysz, M.; Truex, M.; Brady, P.; Newell, C.; Denham, M.

    2011-08-04

    Guidance materials based on use of conceptual model scenarios were developed to assist evaluation and implementation of attenuation-based remedies for groundwater and vadose zones contaminated with inorganic and radionuclide contaminants. The Scenarios approach is intended to complement the comprehensive information provided in the US EPA's Technical Protocol for Monitored Natural Attenuation (MNA) of Inorganic Contaminants by providing additional information on site conceptual models and extending the evaluation to consideration of Enhanced Attenuation approaches. The conceptual models incorporate the notion of reactive facies, defined as units with hydrogeochemical properties that are different from surrounding units and that react with contaminants in distinct ways. The conceptual models also incorporate consideration of biogeochemical gradients, defined as boundaries between different geochemical conditions that have been induced by waste disposal or other natural phenomena. Gradients can change over time when geochemical conditions from one area migrate into another, potentially affecting contaminant mobility. A recognition of gradients allows the attenuation-affecting conditions of a site to be projected into the future. The Scenarios approach provides a stepwise process to identify an appropriate category of conceptual model and refine it for a specific site. Scenario materials provide links to pertinent sections in the EPA technical protocol and present information about contaminant mobility and important controlling mechanism for attenuation-based remedies based on the categories of conceptual models.

  14. Neuroprotective effect of novel cognitive enhancer noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation

    PubMed Central

    2014-01-01

    Background Noopept (N-phenyl-acetyl-L-prolylglycine ethyl ester) was constructed as a dipeptide analog of the standard cognition enhancer, piracetam. Our previous experiments have demonstrated the cognition restoring effect of noopept in several animal models of Alzheimer disease (AD). Noopept was also shown to prevent ionic disbalance, excitotoxicity, free radicals and pro-inflammatory cytokines accumulation, and neurotrophine deficit typical for different kinds of brain damages, including AD. In this study, we investigated the neuroprotective action of noopept on cellular model of AD, Aβ25–35-induced toxicity in PC12 cells and revealed the underlying mechanisms. Results The neuroprotective effect of noopept (added to the medium at 10 μM concentration, 72 hours before Аβ25–35) was studied on Аβ25–35-induced injury (5 μM for 24 h) in PC12 cells. The ability of drug to protect the impairments of cell viability, calcium homeostasis, ROS level, mitochondrial function, tau phosphorylation and neurite outgrowth caused by Аβ25–35 were evaluated. Following the exposure of PC12 cells to Аβ25–35 an increase of the level of ROS, intracellular calcium, and tau phosphorylation at Ser396 were observed; these changes were accompanied by a decrease in cell viability and an increase of apoptosis. Noopept treatment before the amyloid-beta exposure improved PC12 cells viability, reduced the number of early and late apoptotic cells, the levels of intracellular reactive oxygen species and calcium and enhanced the mitochondrial membrane potential. In addition, pretreatment of PC12 cell with noopept significantly attenuated tau hyperphosphorylation at Ser396 and ameliorated the alterations of neurite outgrowth evoked by Аβ25–35. Conclusions Taken together, these data provide evidence that novel cognitive enhancer noopept protects PC12 cell against deleterious actions of Aβ through inhibiting the oxidative damage and calcium overload as well as suppressing

  15. Neuroprotective effect of novel cognitive enhancer noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation.

    PubMed

    Ostrovskaya, Rita U; Vakhitova, Yulia V; Kuzmina, Uliyana Sh; Salimgareeva, Milyausha Kh; Zainullina, Liana F; Gudasheva, Tatiana A; Vakhitov, Vener A; Seredenin, Sergey B

    2014-08-06

    Noopept (N-phenyl-acetyl-L-prolylglycine ethyl ester) was constructed as a dipeptide analog of the standard cognition enhancer, piracetam. Our previous experiments have demonstrated the cognition restoring effect of noopept in several animal models of Alzheimer disease (AD). Noopept was also shown to prevent ionic disbalance, excitotoxicity, free radicals and pro-inflammatory cytokines accumulation, and neurotrophine deficit typical for different kinds of brain damages, including AD. In this study, we investigated the neuroprotective action of noopept on cellular model of AD, Aβ 25-35-induced toxicity in PC12 cells and revealed the underlying mechanisms. The neuroprotective effect of noopept (added to the medium at 10 μM concentration, 72 hours before Аβ 25-35) was studied on Аβ 25-35-induced injury (5 μM for 24 h) in PC12 cells. The ability of drug to protect the impairments of cell viability, calcium homeostasis, ROS level, mitochondrial function, tau phosphorylation and neurite outgrowth caused by Аβ 25-35 were evaluated. Following the exposure of PC12 cells to Аβ 25-35 an increase of the level of ROS, intracellular calcium, and tau phosphorylation at Ser396 were observed; these changes were accompanied by a decrease in cell viability and an increase of apoptosis. Noopept treatment before the amyloid-beta exposure improved PC12 cells viability, reduced the number of early and late apoptotic cells, the levels of intracellular reactive oxygen species and calcium and enhanced the mitochondrial membrane potential. In addition, pretreatment of PC12 cell with noopept significantly attenuated tau hyperphosphorylation at Ser396 and ameliorated the alterations of neurite outgrowth evoked by Аβ25-35. Taken together, these data provide evidence that novel cognitive enhancer noopept protects PC12 cell against deleterious actions of Aβ through inhibiting the oxidative damage and calcium overload as well as suppressing the mitochondrial apoptotic pathway

  16. Citation analysis of scientific categories.

    PubMed

    Patience, Gregory S; Patience, Christian A; Blais, Bruno; Bertrand, Francois

    2017-05-01

    Databases catalogue the corpus of research literature into scientific categories and report classes of bibliometric data such as the number of citations to articles, the number of authors, journals, funding agencies, institutes, references, etc. The number of articles and citations in a category are gauges of productivity and scientific impact but a quantitative basis to compare researchers between categories is limited. Here, we compile a list of bibliometric indicators for 236 science categories and citation rates of the 500 most cited articles of each category. The number of citations per paper vary by several orders of magnitude and are highest in multidisciplinary sciences, general internal medicine, and biochemistry and lowest in literature, poetry, and dance. A regression model demonstrates that citation rates to the top articles in each category increase with the square root of the number of articles in a category and decrease proportionately with the age of the references: articles in categories that cite recent research are also cited more frequently. The citation rate correlates positively with the number of funding agencies that finance the research. The category h-index correlates with the average number of cites to the top 500 ranked articles of each category ([Formula: see text]). Furthermore, only a few journals publish the top 500 cited articles in each category: four journals publish 60% ([Formula: see text]) of these and ten publish 81% ([Formula: see text]).

  17. An overview on therapeutics attenuating amyloid β level in Alzheimer’s disease: targeting neurotransmission, inflammation, oxidative stress and enhanced cholesterol levels

    PubMed Central

    Zhou, Xiaoling; Li, Yifei; Shi, Xiaozhe; Ma, Chun

    2016-01-01

    Alzheimer’s disease (AD) is the most common underlying cause of dementia, and novel drugs for its treatment are needed. Of the different theories explaining the development and progression of AD, “amyloid hypothesis” is the most supported by experimental data. This hypothesis states that the cleavage of amyloid precursor protein (APP) leads to the formation of amyloid beta (Aβ) peptides that congregate with formation and deposition of Aβ plaques in the frontal cortex and hippocampus. Risk factors including neurotransmitter modulation, chronic inflammation, metal-induced oxidative stress and elevated cholesterol levels are key contributors to the disease progress. Current therapeutic strategies abating AD progression are primarily based on anti-acetylcholinesterase (AChE) inhibitors as cognitive enhancers. The AChE inhibitor, donepezil, is proven to strengthen cognitive functions and appears effective in treating moderate to severe AD patients. N-Methyl-D-aspartate receptor antagonist, memantine, is also useful, and its combination with donepezil demonstrated a strong stabilizing effect in clinical studies on AD. Nonsteroidal anti-inflammatory drugs delayed the onset and progression of AD and attenuated cognitive dysfunction. Based upon epidemiological evidence and animal studies, antioxidants emerged as potential AD preventive agents; however, clinical trials revealed inconsistencies. Pharmacokinetic and pharmacodynamic profiling demonstrated pleiotropic functions of the hypolipidemic class of drugs, statins, potentially contributing towards the prevention of AD. In addition, targeting the APP processing pathways, stimulating neuroprotective signaling mechanisms, using the amyloid anti-aggregants and Aβ immunotherapy surfaced as well-tested strategies in reducing the AD-like pathology. Overall, this review covers mechanism of inducing the Aβ formation, key risk factors and major therapeutics prevalent in the AD treatment nowadays. It also delineates the

  18. Putative Dopamine Agonist (KB220Z) Attenuates Lucid Nightmares in PTSD Patients: Role of Enhanced Brain Reward Functional Connectivity and Homeostasis Redeeming Joy

    PubMed Central

    McLaughlin, Thomas; Blum, Kenneth; Oscar-Berman, Marlene; Febo, Marcelo; Agan, Gozde; Fratantonio, James L.; Simpatico, Thomas; Gold, Mark S.

    2015-01-01

    Background Lucid dreams are frequently pleasant and training techniques have been developed to teach dreamers to induce them. In addition, the induction of lucid dreams has also been used as a way to ameliorate nightmares. On the other hand, lucid dreams may be associated with psychiatric conditions, including Post-Traumatic Stress Disorder (PTSD) and Reward Deficiency Syndrome-associated diagnoses. In the latter conditions, lucid dreams can assume an unpleasant and frequently terrifying character. Case Presentations We present two cases of dramatic alleviation of terrifying lucid dreams in patients with PTSD. In the first case study, a 51-year-old, obese woman, diagnosed with PTSD and depression, had attempted suicide and experienced terrifying lucid nightmares linked to sexual/physical abuse from early childhood by family members including her alcoholic father. Her vivid “bad dreams” remained refractory in spite of 6 months of treatment with Dialectical Behavioral Therapy (DBT) and standard pharmaceutical agents which included prazosin, clonidie and Adderall. The second 39-year-old PTSD woman patient had also suffered from lucid nightmares. Results The medication visit notes reveal changes in the frequency, intensity and nature of these dreams after the complex putative dopamine agonist KB220Z was added to the first patient’s regimen. The patient reported her first experience of an extended period of happy dreams. The second PTSD patient, who had suffered from lucid nightmares, was administered KB220Z to attenuate methadone withdrawal symptoms and incidentally reported dreams full of happiness and laughter. Conclusions These cases are discussed with reference to the known effects of KB220Z including enhanced dopamine homeostasis and functional connectivity of brain reward circuitry in rodents and humans. Their understanding awaits intensive investigation involving large-population, double-blinded studies. PMID:26132915

  19. Attenuation of diabetic retinopathy by enhanced inhibition of MMP-2 and MMP-9 using aspirin and minocycline in streptozotocin-diabetic rats.

    PubMed

    Bhatt, Lokesh Kumar; Addepalli, Veeranjaneyulu

    2010-02-12

    Interruptions of Matrix Metalloproteinase-2 (MMP-2) and Matrix Metalloproteinase-9 (MMP-9) have been shown to reduce the ensuing threatening risk factors of vascular complications of diabetes by alteration in Extracellular Matrix (ECM). We hypothesized that minocycline induced MMP-2 and MMP-9 inhibition can be enhanced by aspirin, a non-selective COX and tPA inhibitor and this combination can reduce progression of diabetic retinopathy. Diabetes was induced in male Wistar rats by streptozotocin (55 mg/kg i.p.). Four weeks after diabetes induction rats were treated with minocycline (50 mg/kg, p.o.) per se, aspirin (50 mg/kg, p.o.) per se, or minocycline in combination with aspirin for a period of four weeks. At the end of eighth week rats were anesthetized and electroretinograms were recorded. B-wave latency, B-wave amplitude and retinal permeability were measured. Histology was done and retinal thickness was measured. Zymography was carried out for MMP-2 and MMP-9 level determinations. B-wave amplitude was significantly decreased while B- wave latency was significantly increased in diabetic group when compared with normo-glycemic rats. Treatment with combination of minocycline and aspirin significantly reversed B-wave amplitude and latency compared with vehicle-treated diabetic controls. Blood retinal permeability and retinal thickness were also significantly attenuated by the treatment of minocycline in combination with aspirin. Results of the present study suggest that MMP-2 and MMP-9 inhibition in presence of COX inhibitor prevents the development of experimental diabetic retinopathy in rats and can be a potential approach for the treatment.

  20. NT-PGC-1α activation attenuates high-fat diet-induced obesity by enhancing brown fat thermogenesis and adipose tissue oxidative metabolism.

    PubMed

    Jun, Hee-Jin; Joshi, Yagini; Patil, Yuvraj; Noland, Robert C; Chang, Ji Suk

    2014-11-01

    The transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and its splice variant N terminal (NT)-PGC-1α regulate adaptive thermogenesis by transcriptional induction of thermogenic and mitochondrial genes involved in energy metabolism. We previously reported that full-length PGC-1α (FL-PGC-1α) is dispensable for cold-induced nonshivering thermogenesis in FL-PGC-1α(-/-) mice, since a slightly shorter but functionally equivalent form of NT-PGC-1α (NT-PGC-1α(254)) fully compensates for the loss of FL-PGC-1α in brown and white adipose tissue. In the current study, we challenged FL-PGC-1α(-/-) mice with a high-fat diet (HFD) to investigate the effects of diet-induced thermogenesis on HFD-induced obesity. Despite a large decrease in locomotor activity, FL-PGC-1α(-/-) mice exhibited the surprising ability to attenuate HFD-induced obesity. Reduced fat mass in FL-PGC-1α(-/-) mice was closely associated with an increase in body temperature, energy expenditure, and whole-body fatty acid oxidation (FAO). Mechanistically, FL-PGC-1α(-/-) brown adipose tissue had an increased capacity to oxidize fatty acids and dissipate energy as heat, in accordance with upregulation of thermogenic genes UCP1 and DIO2. Furthermore, augmented expression of FAO and lipolytic genes in FL-PGC-1α(-/-) white adipose tissue was highly correlated with decreased fat storage in adipose tissue. Collectively, our data highlight a protective effect of NT-PGC-1α on diet-induced obesity by enhancing diet-induced thermogenesis and FAO.

  1. Ultrasound-enhanced attenuated total reflection mid-infrared spectroscopy in-line probe: acquisition of cell spectra in a bioreactor.

    PubMed

    Koch, Cosima; Brandstetter, Markus; Wechselberger, Patrick; Lorantfy, Bettina; Plata, Maria Reyes; Radel, Stefan; Herwig, Christoph; Lendl, Bernhard

    2015-02-17

    This article presents a novel method for selective acquisition of Fourier transform infrared (FT-IR) spectra of microorganisms in-line during fermentation, using Saccharomyces cerevisiae as an example. The position of the cells relative to the sensitive region of the attenuated total reflection (ATR) FT-IR probe was controlled by combing a commercially available ATR in-line probe with contact-free, gentle particle manipulation by ultrasonic standing waves. A prototype probe was successfully constructed, assembled, and tested in-line during fed-batch fermentations of S. cerevisiae. Control over the position of the cells was achieved by tuning the ultrasound frequency: 2.41 MHz was used for acquisition of spectra of the cells (pushing frequency f(p)) and 1.87 MHz, for retracting the cells from the ATR element, therefore allowing spectra of the medium to be acquired. Accumulation of storage carbohydrates (trehalose and glycogen) inside the cells was induced by a lack of a nitrogen source in the feed medium. These changes in biochemical composition were visible in the spectra of the cells recorded in-line during the application of f(p) and could be verified by reference spectra of dried cell samples recorded off-line with a FT-IR microscope. Comparison of the cell spectra with spectra of trehalose, glycogen, glucose, and mannan, i.e., the major carbohydrates present in S. cerevisiae, and principal components analysis revealed that the changes observed in the cell spectra correlated well with the bands specific for trehalose and glycogen. This proves the applicability and capability of ultrasound-enhanced in-line ATR mid-IR spectroscopy as a real-time PAT method for the in situ monitoring of cellular biochemistry during fermentation.

  2. Ultrasound-Enhanced Attenuated Total Reflection Mid-infrared Spectroscopy In-Line Probe: Acquisition of Cell Spectra in a Bioreactor

    PubMed Central

    2015-01-01

    This article presents a novel method for selective acquisition of Fourier transform infrared (FT-IR) spectra of microorganisms in-line during fermentation, using Saccharomyces cerevisiae as an example. The position of the cells relative to the sensitive region of the attenuated total reflection (ATR) FT-IR probe was controlled by combing a commercially available ATR in-line probe with contact-free, gentle particle manipulation by ultrasonic standing waves. A prototype probe was successfully constructed, assembled, and tested in-line during fed-batch fermentations of S. cerevisiae. Control over the position of the cells was achieved by tuning the ultrasound frequency: 2.41 MHz was used for acquisition of spectra of the cells (pushing frequency fp) and 1.87 MHz, for retracting the cells from the ATR element, therefore allowing spectra of the medium to be acquired. Accumulation of storage carbohydrates (trehalose and glycogen) inside the cells was induced by a lack of a nitrogen source in the feed medium. These changes in biochemical composition were visible in the spectra of the cells recorded in-line during the application of fp and could be verified by reference spectra of dried cell samples recorded off-line with a FT-IR microscope. Comparison of the cell spectra with spectra of trehalose, glycogen, glucose, and mannan, i.e., the major carbohydrates present in S. cerevisiae, and principal components analysis revealed that the changes observed in the cell spectra correlated well with the bands specific for trehalose and glycogen. This proves the applicability and capability of ultrasound-enhanced in-line ATR mid-IR spectroscopy as a real-time PAT method for the in situ monitoring of cellular biochemistry during fermentation. PMID:25582569

  3. Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients: role of enhanced brain reward functional connectivity and homeostasis redeeming joy.

    PubMed

    McLaughlin, Thomas; Blum, Kenneth; Oscar-Berman, Marlene; Febo, Marcelo; Agan, Gozde; Fratantonio, James L; Simpatico, Thomas; Gold, Mark S

    2015-06-01

    Lucid dreams are frequently pleasant and training techniques have been developed to teach dreamers to induce them. In addition, the induction of lucid dreams has also been used as a way to ameliorate nightmares. On the other hand, lucid dreams may be associated with psychiatric conditions, including Post-Traumatic Stress Disorder (PTSD) and Reward Deficiency Syndrome-associated diagnoses. In the latter conditions, lucid dreams can assume an unpleasant and frequently terrifying character. We present two cases of dramatic alleviation of terrifying lucid dreams in patients with PTSD. In the first case study, a 51-year-old, obese woman, diagnosed with PTSD and depression, had attempted suicide and experienced terrifying lucid nightmares linked to sexual/physical abuse from early childhood by family members including her alcoholic father. Her vivid "bad dreams" remained refractory in spite of 6 months of treatment with Dialectical Behavioral Therapy (DBT) and standard pharmaceutical agents which included prazosin, clonidie and Adderall. The second 39-year-old PTSD woman patient had also suffered from lucid nightmares. The medication visit notes reveal changes in the frequency, intensity and nature of these dreams after the complex putative dopamine agonist KB220Z was added to the first patient's regimen. The patient reported her first experience of an extended period of happy dreams. The second PTSD patient, who had suffered from lucid nightmares, was administered KB220Z to attenuate methadone withdrawal symptoms and incidentally reported dreams full of happiness and laughter. These cases are discussed with reference to the known effects of KB220Z including enhanced dopamine homeostasis and functional connectivity of brain reward circuitry in rodents and humans. Their understanding awaits intensive investigation involving large-population, double-blinded studies.

  4. INHIBITION OF PAN NEUROTROPHIN RECEPTOR P75 ATTENUATES DIESEL PARTICULATE-INDUCED ENHANCEMENT OF ALLERGIC AIRWAY RESPONSES IN C57/BL6J MICE

    EPA Science Inventory

    Recent investigations have linked neurotrophins including nerve growth factor (NGF), neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF) to allergic airways diseases. Antibody blockade of NGF attenuates airway resistance in allergic mice. Diesel exhaust particle...

  5. INHIBITION OF PAN NEUROTROPHIN RECEPTOR P75 ATTENUATES DIESEL PARTICULATE-INDUCED ENHANCEMENT OF ALLERGIC AIRWAY RESPONSES IN C57/BL6J MICE

    EPA Science Inventory

    Recent investigations have linked neurotrophins including nerve growth factor (NGF), neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF) to allergic airways diseases. Antibody blockade of NGF attenuates airway resistance in allergic mice. Diesel exhaust particle...

  6. Orienting attention to semantic categories

    PubMed Central

    Cristescu, Tamara C.; Devlin, Joseph T.; Nobre, Anna C.

    2006-01-01

    We investigated the ability to orient attention to a complex, non-perceptual attribute of stimuli—semantic category. Behavioral consequences and neural correlates of semantic orienting were revealed and compared with those of spatial orienting, using event-related functional magnetic-resonance imaging. Semantic orienting significantly shortened response times to identify word stimuli, showing that it is possible to focus attention on non-perceptual attributes of stimuli to enhance behavioral performance. Semantic-orienting cues engaged parietal and frontal areas that were also involved in spatial orienting, but in addition engaged brain areas associated with semantic analysis of words, such as the left anterior inferior frontal cortex. These findings show that attentional orienting selectively engages brain areas with functional specialization for the predicted attributes. They also support the existence of a core frontoparietal network, which controls attentional orienting in speeded response tasks independently of the type of expectations, interacting with task-relevant functionally specialized areas to optimize perception and action. PMID:17011212

  7. Category vs. Object Knowledge in Category-Based Induction

    ERIC Educational Resources Information Center

    Murphy, Gregory L.; Ross, Brian H.

    2010-01-01

    In one form of category-based induction, people make predictions about unknown properties of objects. There is a tension between predictions made based on the object's specific features (e.g., objects above a certain size tend not to fly) and those made by reference to category-level knowledge (e.g., birds fly). Seven experiments with artificial…

  8. Category vs. Object Knowledge in Category-Based Induction

    ERIC Educational Resources Information Center

    Murphy, Gregory L.; Ross, Brian H.

    2010-01-01

    In one form of category-based induction, people make predictions about unknown properties of objects. There is a tension between predictions made based on the object's specific features (e.g., objects above a certain size tend not to fly) and those made by reference to category-level knowledge (e.g., birds fly). Seven experiments with artificial…

  9. Category vs. Object Knowledge in Category-based Induction

    PubMed Central

    Murphy, Gregory L.; Ross, Brian H.

    2009-01-01

    In one form of category-based induction, people make predictions about unknown properties of objects. There is a tension between predictions made based on the object’s specific features (e.g., objects above a certain size tend not to fly) and those made by reference to category-level knowledge (e.g., birds fly). Seven experiments with artificial categories investigated these two sources of induction by looking at whether people used information about correlated features within categories, suggesting that they focused on feature-feature relations rather than summary categorical information. The results showed that people relied heavily on such correlations, even when there was no reason to think that the correlations exist in the population. The results suggested that people’s use of this strategy is largely unreflective, rather than strategically chosen. These findings have important implications for models of category-based induction, which generally ignore feature-feature relations. PMID:20526447

  10. The Coordination of Unlike Categories.

    ERIC Educational Resources Information Center

    Bayer, Samuel

    1996-01-01

    Argues that the account of coordination of unlike categories ought to be unified with the account of feature neutralization under phonological identity. Further argues that this unified account ought not be couched in terms of string of features, but rather in terms of the logic of categories. Study concludes with a discussion of the interactions…

  11. The Coordination of Unlike Categories.

    ERIC Educational Resources Information Center

    Bayer, Samuel

    1996-01-01

    Argues that the account of coordination of unlike categories ought to be unified with the account of feature neutralization under phonological identity. Further argues that this unified account ought not be couched in terms of string of features, but rather in terms of the logic of categories. Study concludes with a discussion of the interactions…

  12. Identification of Prelinguistic Phonological Categories

    ERIC Educational Resources Information Center

    Ramsdell, Heather L.; Oller, D. Kimbrough; Buder, Eugene H.; Ethington, Corinna A.; Chorna, Lesya

    2012-01-01

    Purpose: The prelinguistic infant's babbling repertoire of "syllables"--the phonological categories that form the basis for early word learning--is noticed by caregivers who interact with infants around them. Prior research on babbling has not explored the caregiver's role in recognition of early vocal categories as foundations for word learning.…

  13. Enhanced expression of HIV and SIV vaccine antigens in the structural gene region of live attenuated rubella viral vectors and their incorporation into virions.

    PubMed

    Virnik, Konstantin; Ni, Yisheng; Berkower, Ira

    2013-04-19

    Despite the urgent need for an HIV vaccine, its development has been hindered by virus variability, weak immunogenicity of conserved epitopes, and limited durability of the immune response. For other viruses, difficulties with immunogenicity were overcome by developing live attenuated vaccine strains. However, there is no reliable method of attenuation for HIV, and an attenuated strain would risk reversion to wild type. We have developed rubella viral vectors, based on the live attenuated vaccine strain RA27/3, which are capable of expressing important HIV and SIV vaccine antigens. The rubella vaccine strain has demonstrated safety, immunogenicity, and long lasting protection in millions of children. Rubella vectors combine the growth and immunogenicity of live rubella vaccine with the antigenicity of HIV or SIV inserts. This is the first report showing that live attenuated rubella vectors can stably express HIV and SIV vaccine antigens at an insertion site located within the structural gene region. Unlike the Not I site described previously, the new site accommodates a broader range of vaccine antigens without interfering with essential viral functions. In addition, antigens expressed at the structural site were controlled by the strong subgenomic promoter, resulting in higher levels and longer duration of antigen expression. The inserts were expressed as part of the structural polyprotein, processed to free antigen, and incorporated into rubella virions. The rubella vaccine strain readily infects rhesus macaques, and these animals will be the model of choice for testing vector growth in vivo and immunogenicity.

  14. Cholesterol reduction by methyl-β-cyclodextrin attenuates the delta opioid receptor-mediated signaling in neuronal cells but enhances it in non-neuronal cells

    PubMed Central

    Huang, Peng; Xu, Wei; Yoon, Su-In; Chen, Chongguang; Chong, Parkson Lee-Gau; Liu-Chen, Lee-Yuan

    2008-01-01

    Opioid receptors have been shown to be located in and regulated by lipid rafts/caveolae in caveolin-rich non-neuronal cells. Here, we found that caveolin-1 level was very low in rat brain and undetectable in NG108-15 cells, which endogenously express delta opioid receptors (DOR). Rat caudate putamen (CPu) membranes, NG108-15 cells and CHO cells stably transfected with FLAG-mouse-DOR (CHO-FLAG-mDOR) were homogenized, sonicated in a detergent-free 0.5 M Na2CO3 buffer and fractionated through discontinuous or continuous sucrose density gradients. About 70% of opioid receptors in CPu and DOR in both cell lines were present in low-density (5-20% sucrose) membrane-domains enriched in cholesterol and ganglioside M1 (GM1), characteristics of lipid rafts in plasma membranes. In both cells, stimulation with permeable or non-permeable full agonists, but not with partial or inverse agonists, for 30 min shifted ∼25% of DORs out of rafts, by a naloxone-reversible and pertussis toxin-insensitive mechanism, which may undergo internalization. Methyl-β-cyclodextrin (MCD) treatment greatly reduced cholesterol and shifted DOR to higher-density fractions and decreased DPDPE affinities. MCD treatment attenuated DPDPE-induced [35S]GTPγS binding in CPu and NG108-15 cells, but enhanced it in CHO-FLAG-mDOR cells. In CHO-FLAG-mDOR cells, Gαi co-immunoprecipitated with caveolin-1, which was shown to inhibit Gαi/o, and MCD treatment dramatically reduced the association leading to disinhibition. Thus, although localization in rafts and agonist-induced shift of DOR are independent of caveolin-1, lipid rafts sustain DOR-mediated signaling in caveolin-deficient neuronal cells, but appear to inhibit it in caveolin-enriched non-neuronal cells. Cholesterol-dependent association of caveolin-1 with and the resulting inhibition of G proteins may be a contributing factor. PMID:17141202

  15. Consumption of dairy yogurt with the polysaccharide rhamnogalacturonan from the peel of the Korean citrus hallabong enhances immune function and attenuates the inflammatory response.

    PubMed

    Lee, Mi-Hyang; Kim, Minjoo; Kim, Minkyung; Kwak, Jung Hyun; Chang, Dong Hoon; Yu, Won Kyu; Lee, Sang-Hyun; Lee, Jong Ho

    2016-06-15

    The aim of this study was to investigate the impact of consuming dairy yogurt supplemented with rhamnogalacturonan (RG), a polysaccharide from the peel of the Korean citrus hallabong, on natural killer (NK) cell activity and circulating cytokine levels. A randomized, double-blind, placebo-controlled study was conducted on 120 nondiabetic and nonobese subjects. Over an eight-week period, the test group consumed one pack (150 mL) of dairy yogurt containing 50 mg of probiotics and 100 mg of hallabong peel polysaccharide (60% RG) each day, whereas the placebo group consumed the same product without the hallabong peel supplement. NK cell activity (%) was measured based on the ratios of the effector cells (E; peripheral blood mononuclear cells, PBMCs) from each participant relative to the target cells (T; K562 cells) at E : T ratios of 10 : 1, 5 : 1, 2.5 : 1, or 1.25 : 1. NK cell activities under all assay conditions and interleukin (IL)-12 and interferon (IFN)-γ levels were significantly increased in the test group at eight weeks compared to the baseline values, whereas the placebo group showed a significant increase only in NK cell activity at E : T = 1.25 : 1. The test group had significantly greater increases in the changes in serum NK cell activity at the E : T ratios of 10 : 1, 5 : 1, and 2.5 : 1 and in the increases in IL-12 and IFN-γ levels than were observed in the placebo group, after adjusting for baseline values. After eight weeks of treatment, significant reductions were found in IL-6 and IL-1β levels in both the placebo and test groups. The daily consumption of dairy yogurt supplemented with RG, a polysaccharide from the peel of the Korean citrus hallabong, enhanced NK cell function and attenuated pro-inflammatory cytokine levels (ClinicalTrials.gov: NCT02535663).

  16. The way to a man's heart is through his stomach: much 'diaphragmatic' attenuation is likely gastric, and effervescent granules enhance cardiac imaging.

    PubMed

    Munn, Samson

    2004-12-01

    Avoidance of falsely positive results depends on distinguishing reality from artifact, in turn depending on images of highest quality. In radionuclide cardiac imaging, an inferior wall artifactual defect, so called "diaphragmatic attenuation", is particularly common and vexing. Despite the historically held view, analysis and review of the literature suggest the defect is likely not diaphragmatic but rather primarily due to attenuation by nearby stomach wall. The explanation is based on gravity and anatomy. With this improved understanding, effervescent granules were given as a clinical, nonresearch measure to nine patients during myocardial scanning. It was observed that two-thirds demonstrated moderate or marked lessening of attenuation. An additional benefit is lessening of artifact by extracardiac activity. These benefits may also apply to other sorts of cardiac radionuclide imaging. The significance of this new imaging method is discussed and various avenues of research are proposed.

  17. Category norms for 500 Spanish words in five semantic categories.

    PubMed

    Izura, Cristina; Hernández-Muñoz, Natividad; Ellis, Andrew W

    2005-08-01

    This study presents a database of 500 words from five semantic categories: animals, body parts, furniture, clothing, and intelligence. Each category contains 100 words, and data on lexical availability, age of acquisition, imageability, typicality, concept familiarity, written word frequency, and word length in number of syllables are provided with each word. The full set of norms may be downloaded from www.psychonomic.org/archive.

  18. Biased allocation of faces to social categories.

    PubMed

    Dotsch, Ron; Wigboldus, Daniël H J; van Knippenberg, Ad

    2011-06-01

    Three studies show that social categorization is biased at the level of category allocation. In all studies, participants categorized faces. In Studies 1 and 2, participants overallocated faces with criminal features--a stereotypical negative trait--to the stigmatized Moroccan category, especially if they were prejudiced. On the contrary, the stereotype-irrelevant negative trait stupid did not lead to overallocation to the Moroccan category. In Study 3, using the stigmatized category homosexual, the previously used negative trait criminal--irrelevant to the homosexual stereotype--did not lead to overallocation, but the stereotype-relevant positive trait femininity did. These results demonstrate that normative fit is higher for faces with stereotype-relevant features regardless of valence. Moreover, individual differences in implicit prejudice predicted the extent to which stereotype-relevant traits elicited overallocation: Whereas more negatively prejudiced people showed greater overallocation of faces associated with negative stereotype-relevant traits, they showed less overallocation of faces associated with positive stereotype-relevant traits. These results support our normative fit hypothesis: In general, normative fit is better for faces with stereotypical features. Moreover, normative fit is enhanced for prejudiced individuals when these features are evaluatively congruent. Social categorization thus may be biased in itself.

  19. Co-administration of attenuated Mycoplasma hyopneumoniae 168 strain with bacterial DNA enhances the local and systemic immune response after intranasal vaccination in pigs.

    PubMed

    Li, Yunfeng; Li, Pengcheng; Wang, Xueping; Yu, Qinghua; Yang, Qian

    2012-03-09

    Mycoplasma hyopneumoniae, the primary pathogen of enzootic pneumonia, occurs worldwide and causes major economic losses to the pig industry. M. hyopneumoniae infects pigs at mucosal surfaces of respiratory tract. The aim of the present study was to investigate if the protection rate against M. hyopneumoniae infection following intranasal immunization with attenuated M. hyopneumoniae 168 strain is improved by administration of bacterial DNA containing CpG motifs. Thirty pigs were immunized intranasally or intramuscularly and the levels of local respiratory tract and systemic immune responses were detected. The results showed that the number of intraepithelial lymphocytes in the tracheal fork, the levels of cytokine IL-6, and M. hyopneumoniae specific SIgA in local nasal cavity increased respectively after intranasal vaccination with the attenuated M. hyopneumoniae 168 strain alone. However, the levels of IL-10 and IFN-γ in local nasal cavity, the number of intraepithelial lymphocytes in trachea, CD4(+) and CD8(+) T lymphocytes in the lung and hilar lymph nodes, the specific IgG antibody level in serum on 35 day post immunization were all increased significantly after intranasal vaccination of the attenuated M. hyopneumoniae 168 strain adjuvanted with bacterial DNA. We concluded that intranasal administration of attenuated M. hyopneumoniae 168 strain adjuvanted with bacterial DNA may be effective in evoking the local cellular and humoral immune response in the respiratory tract and the systemic immune response. Intranasal vaccination will be effective in prevention of the transmission and prevalence of MPS.

  20. Dual-learning systems during speech category learning.

    PubMed

    Chandrasekaran, Bharath; Yi, Han-Gyol; Maddox, W Todd

    2014-04-01

    Dual-system models of visual category learning posit the existence of an explicit, hypothesis-testing reflective system, as well as an implicit, procedural-based reflexive system. The reflective and reflexive learning systems are competitive and neurally dissociable. Relatively little is known about the role of these domain-general learning systems in speech category learning. Given the multidimensional, redundant, and variable nature of acoustic cues in speech categories, our working hypothesis is that speech categories are learned reflexively. To this end, we examined the relative contribution of these learning systems to speech learning in adults. Native English speakers learned to categorize Mandarin tone categories over 480 trials. The training protocol involved trial-by-trial feedback and multiple talkers. Experiments 1 and 2 examined the effect of manipulating the timing (immediate vs. delayed) and information content (full vs. minimal) of feedback. Dual-system models of visual category learning predict that delayed feedback and providing rich, informational feedback enhance reflective learning, while immediate and minimally informative feedback enhance reflexive learning. Across the two experiments, our results show that feedback manipulations that targeted reflexive learning enhanced category learning success. In Experiment 3, we examined the role of trial-to-trial talker information (mixed vs. blocked presentation) on speech category learning success. We hypothesized that the mixed condition would enhance reflexive learning by not allowing an association between talker-related acoustic cues and speech categories. Our results show that the mixed talker condition led to relatively greater accuracies. Our experiments demonstrate that speech categories are optimally learned by training methods that target the reflexive learning system.

  1. Enhancing the quality of radiographic images acquired with point-like gamma-ray sources through correction of the beam divergence and attenuation

    NASA Astrophysics Data System (ADS)

    Silvani, M. I.; Almeida, G. L.; Lopes, R. T.

    2014-11-01

    Radiographic images acquired with point-like gamma-ray sources exhibit a desirable low penumbra effects specially when positioned far away from the set object-detector. Such an arrangement frequently is not affordable due to the limited flux provided by a distant source. A closer source, however, has two main drawbacks, namely the degradation of the spatial resolution - as actual sources are only approximately punctual - and the non-homogeneity of the beam hitting the detector, which creates a false attenuation map of the object being inspected. This non-homogeneity is caused by the beam divergence itself and by the different thicknesses traversed the beam even if the object were an homogeneous flat plate. In this work, radiographic images of objects with different geometries, such as flat plates and pipes have undergone a correction of beam divergence and attenuation addressing the experimental verification of the capability and soundness of an algorithm formerly developed to generate and process synthetic images. The impact of other parameters, including source-detector gap, attenuation coefficient, ratio defective-to-main hull thickness and counting statistics have been assessed for specifically tailored test-objects aiming at the evaluation of the ability of the proposed method to deal with different boundary conditions. All experiments have been carried out with an X-ray sensitive Imaging Plate and reactor-produced 198Au and 165Dy sources. The results have been compared with other technique showing a better capability to correct the attenuation map of inspected objects unveiling their inner structure otherwise concealed by the poor contrast caused by the beam divergence and attenuation, in particular for those regions far apart from the vertical of the source.

  2. Psychopathic disorder: a category mistake?

    PubMed Central

    Holmes, C A

    1991-01-01

    Although the concept of psychopathy retains its currency in British psychiatry, apparently being meaningful as well as useful to practitioners (1), it is often taken to refer to a purely legal category with social control functions rather than a medical diagnosis with treatment implications. I wish, in this brief article, to suggest that it is essentially, and most usefully, an ethical category which stands outside the diagnostic framework of present-day psychiatry. PMID:1870086

  3. Natural attenuation software (NAS): Assessing remedial strategies and estimating timeframes

    USGS Publications Warehouse

    Mendez, E.; Widdowson, M.; Chapelle, F.; Casey, C.

    2005-01-01

    Natural Attenuation Software (NAS) is a screening tool to estimate remediation timeframes for monitored natural attenuation (MNA) and to assist in decision-making on the level of source zone treatment in conjunction with MNA using site-specific remediation objectives. Natural attenuation processes that NAS models include are advection, dispersion, sorption, non-aqueous phase liquid (NAPL) dissolution, and biodegradation of either petroleum hydrocarbons or chlorinated ethylenes. Newly-implemented enhancements to NAS designed to maximize the utility of NAS for site managers were observed. NAS has expanded source contaminant specification options to include chlorinated ethanes and chlorinated methanes, and to allow for the analysis of any other user-defined contaminants that may be subject to microbially-mediated transformations (heavy metals, radioisotopes, etc.). Included is the capability to model co-mingled plumes, with constituents from multiple contaminant categories. To enable comparison of remediation timeframe estimates between MNA and specific engineered remedial actions , NAS was modified to incorporate an estimation technique for timeframes associated with pump-and-treat remediation technology for comparison to MNA. This is an abstract of a paper presented at the 8th International In Situ and On-Site Bioremediation Symposium (Baltimore, MD 6/6-9/2005).

  4. Data categories for marine planning

    USGS Publications Warehouse

    Lightsom, Frances L.; Cicchetti, Giancarlo; Wahle, Charles M.

    2015-01-01

    The U.S. National Ocean Policy calls for a science- and ecosystem-based approach to comprehensive planning and management of human activities and their impacts on America’s oceans. The Ocean Community in Data.gov is an outcome of 2010–2011 work by an interagency working group charged with designing a national information management system to support ocean planning. Within the working group, a smaller team developed a list of the data categories specifically relevant to marine planning. This set of categories is an important consensus statement of the breadth of information types required for ocean planning from a national, multidisciplinary perspective. Although the categories were described in a working document in 2011, they have not yet been fully implemented explicitly in online services or geospatial metadata, in part because authoritative definitions were not created formally. This document describes the purpose of the data categories, provides definitions, and identifies relations among the categories and between the categories and external standards. It is intended to be used by ocean data providers, managers, and users in order to provide a transparent and consistent framework for organizing and describing complex information about marine ecosystems and their connections to humans.

  5. Anyon condensation and tensor categories

    NASA Astrophysics Data System (ADS)

    Kong, Liang

    2014-09-01

    Instead of studying anyon condensation in various concrete models, we take a bootstrap approach by considering an abstract situation, in which an anyon condensation happens in a 2-d topological phase with anyonic excitations given by a modular tensor category C; and the anyons in the condensed phase are given by another modular tensor category D. By a bootstrap analysis, we derive a relation between anyons in D-phase and anyons in C-phase from natural physical requirements. It turns out that the vacuum (or the tensor unit) A in D-phase is necessary to be a connected commutative separable algebra in C, and the category D is equivalent to the category of local A-modules as modular tensor categories. This condensation also produces a gapped domain wall with wall excitations given by the category of A-modules in C. A more general situation is also studied in this paper. We will also show how to determine such algebra A from the initial and final data. Multi-condensations and 1-d condensations will also be briefly discussed. Examples will be given in the toric code model, Kitaev quantum double models, Levin-Wen types of lattice models and some chiral topological phases.

  6. Electrophysiological correlates of category goodness.

    PubMed

    Rivera-Gaxiola, M; Johnson, M H; Csibra, G; Karmiloff-Smith, A

    2000-07-01

    We report the results obtained from a behavioural and electrophysiological study. A synthesised continuum going from labial /ba/ to retroflex /da/ through dental /da/ was tested for category goodness. Native English speakers rated different tokens from each category as good, bad or ambiguous. The results showed that not all of the representatives of each category were ideal and that the categories tested have an internal structure. The electrophysiological study evaluated whether event related potentials (ERPs) mirrored the goodness judgements. During a passive oddball task, the same participants were exposed to native /ba/-/da/, Hindi dental /da/-retroflex /da/ and within-category /ba/-/ba/ contrasts. Results showed that participants pre-attentively perceive the differences in all cases, as shown by mis-match negativities (MMN), late positive deflections (LPD) or greater N1 and/or P2 components for deviant stimuli. Acoustic sensitivities, categorical perception and category goodness all contributed to the waveforms obtained. We attribute the ERP effects to a combination of (1) prototypes built from initial sensitivities, (2) reinforcement with exposure to one's native language and (3) no permanent loss of the initial boundaries explains the effects observed.

  7. Rotary antenna attenuator

    NASA Technical Reports Server (NTRS)

    Dickinson, R. M.; Hardy, J. C.

    1969-01-01

    Radio frequency attenuator, having negligible insertion loss at minimum attenuation, can be used for making precise antenna gain measurements. It is small in size compared to a rotary-vane attenuator.

  8. Aversive Learning Modulates Cortical Representations of Object Categories

    PubMed Central

    Dunsmoor, Joseph E.; Kragel, Philip A.; Martin, Alex; LaBar, Kevin S.

    2014-01-01

    Experimental studies of conditioned learning reveal activity changes in the amygdala and unimodal sensory cortex underlying fear acquisition to simple stimuli. However, real-world fears typically involve complex stimuli represented at the category level. A consequence of category-level representations of threat is that aversive experiences with particular category members may lead one to infer that related exemplars likewise pose a threat, despite variations in physical form. Here, we examined the effect of category-level representations of threat on human brain activation using 2 superordinate categories (animals and tools) as conditioned stimuli. Hemodynamic activity in the amygdala and category-selective cortex was modulated by the reinforcement contingency, leading to widespread fear of different exemplars from the reinforced category. Multivariate representational similarity analyses revealed that activity patterns in the amygdala and object-selective cortex were more similar among exemplars from the threat versus safe category. Learning to fear animate objects was additionally characterized by enhanced functional coupling between the amygdala and fusiform gyrus. Finally, hippocampal activity co-varied with object typicality and amygdala activation early during training. These findings provide novel evidence that aversive learning can modulate category-level representations of object concepts, thereby enabling individuals to express fear to a range of related stimuli. PMID:23709642

  9. Aversive learning modulates cortical representations of object categories.

    PubMed

    Dunsmoor, Joseph E; Kragel, Philip A; Martin, Alex; LaBar, Kevin S

    2014-11-01

    Experimental studies of conditioned learning reveal activity changes in the amygdala and unimodal sensory cortex underlying fear acquisition to simple stimuli. However, real-world fears typically involve complex stimuli represented at the category level. A consequence of category-level representations of threat is that aversive experiences with particular category members may lead one to infer that related exemplars likewise pose a threat, despite variations in physical form. Here, we examined the effect of category-level representations of threat on human brain activation using 2 superordinate categories (animals and tools) as conditioned stimuli. Hemodynamic activity in the amygdala and category-selective cortex was modulated by the reinforcement contingency, leading to widespread fear of different exemplars from the reinforced category. Multivariate representational similarity analyses revealed that activity patterns in the amygdala and object-selective cortex were more similar among exemplars from the threat versus safe category. Learning to fear animate objects was additionally characterized by enhanced functional coupling between the amygdala and fusiform gyrus. Finally, hippocampal activity co-varied with object typicality and amygdala activation early during training. These findings provide novel evidence that aversive learning can modulate category-level representations of object concepts, thereby enabling individuals to express fear to a range of related stimuli. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Prognosis of Hurricanes CATEGORIE-5

    NASA Astrophysics Data System (ADS)

    Perez-Peraza, Jorge; Velasco Herrera, Victor Manuel; Zapotitla Roman, Julian; Juarez Zuñiga, Alan

    Category-5 Hurricanes are the most devastating from the standpoint of human and economic losses. Approximately 80 cyclones per year occurring worldwide, from which 8.8 per year occur on average in different regions of the Atlantic. However, category-5 Hurricanes do not follow a cyclic pattern but ar rather of quasi-stochastic nature. To assist in the alert processes o of hurricanes, we propose here a method to predict those kinds of hurricanes based on the Wavelet Analysis and applying techniques of Fuzzy Logic. For our study we consider North Atlantic category-5 hurricanes since 1920. Data was transformed into a series of Pulses with unitary value at the dates of hurricanes occurrence and 0 for dates of no occurrence. By means of the Wavelet transform we determine dominant oscillation periods. Under the hypothesis that the occurrence of hurricanes of this category can be described by the certain periodicities, we can define the dominant periods of oscillation and establish correspondence rules using fuzzy logic. The fuzzy logic searches for associations between the hurricanes occurrence and the behavior of the harmonics, and then delimits the occurrence of the next hurricane. The Wavelet Power Spectrum yields the following periodicities 2, 9, 14 and 24 years. According to the behavior of the harmonics we found that their combination restricts regions of possible Hurricane occurrence. Interpolation of this sinusoidal behavior allows for a good reconstruction of past Hurricanes dates as well as extrapolation to the future. In this way we conclude that there is a good probability that the next category-5 Hurricane in the north Atlantic occur of 2014-2015. Regarding categorie-5 typhoons in the pacific we delimitate the genesis regions of western of these kind of typhoons.

  11. DC attenuation meter

    DOEpatents

    Hargrove, Douglas L.

    2004-09-14

    A portable, hand-held meter used to measure direct current (DC) attenuation in low impedance electrical signal cables and signal attenuators. A DC voltage is applied to the signal input of the cable and feedback to the control circuit through the signal cable and attenuators. The control circuit adjusts the applied voltage to the cable until the feedback voltage equals the reference voltage. The "units" of applied voltage required at the cable input is the system attenuation value of the cable and attenuators, which makes this meter unique. The meter may be used to calibrate data signal cables, attenuators, and cable-attenuator assemblies.

  12. Polyphenolic Extract of Euphorbia supina Attenuates Manganese-Induced Neurotoxicity by Enhancing Antioxidant Activity through Regulation of ER Stress and ER Stress-Mediated Apoptosis.

    PubMed

    Bahar, Entaz; Lee, Geum-Hwa; Bhattarai, Kashi Raj; Lee, Hwa-Young; Choi, Min-Kyung; Rashid, Harun-Or; Kim, Ji-Ye; Chae, Han-Jung; Yoon, Hyonok

    2017-01-30

    Manganese (Mn) is an important trace element present in human body, which acts as an enzyme co-factor or activator in various metabolic reactions. While essential in trace amounts, excess levels of Mn in human brain can produce neurotoxicity, including idiopathic Parkinson's disease (PD)-like extrapyramidal manganism symptoms. This study aimed to investigate the protective role of polyphenolic extract of Euphorbia supina (PPEES) on Mn-induced neurotoxicity and the underlying mechanism in human neuroblastoma SKNMC cells and Sprague-Dawley (SD) male rat brain. PPEES possessed significant amount of total phenolic and flavonoid contents. PPEES also showed significant antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and reducing power capacity (RPC) assays. Our results showed that Mn treatment significantly reduced cell viability and increased lactate dehydrogenase (LDH) level, which was attenuated by PPEES pretreatment at 100 and 200 µg/mL. Additionally, PPEES pretreatment markedly attenuated Mn-induced antioxidant status alteration by resolving the ROS, MDA and GSH levels and SOD and CAT activities. PPEES pretreatment also significantly attenuated Mn-induced mitochondrial membrane potential (ΔΨm) and apoptosis. Meanwhile, PPEES pretreatment significantly reversed the Mn-induced alteration in the GRP78, GADD34, XBP-1, CHOP, Bcl-2, Bax and caspase-3 activities. Furthermore, administration of PPEES (100 and 200 mg/kg) to Mn exposed rats showed improvement of histopathological alteration in comparison to Mn-treated rats. Moreover, administration of PPEES to Mn exposed rats showed significant reduction of 8-OHdG and Bax immunoreactivity. The results suggest that PPEES treatment reduces Mn-induced oxidative stress and neuronal cell loss in SKNMC cells and in the rat brain. Therefore, PPEES may be considered as potential treat-ment in Mn-intoxicated patients.

  13. Polyphenolic Extract of Euphorbia supina Attenuates Manganese-Induced Neurotoxicity by Enhancing Antioxidant Activity through Regulation of ER Stress and ER Stress-Mediated Apoptosis

    PubMed Central

    Bahar, Entaz; Lee, Geum-Hwa; Bhattarai, Kashi Raj; Lee, Hwa-Young; Choi, Min-Kyung; Rashid, Harun-Or; Kim, Ji-Ye; Chae, Han-Jung; Yoon, Hyonok

    2017-01-01

    Manganese (Mn) is an important trace element present in human body, which acts as an enzyme co-factor or activator in various metabolic reactions. While essential in trace amounts, excess levels of Mn in human brain can produce neurotoxicity, including idiopathic Parkinson’s disease (PD)-like extrapyramidal manganism symptoms. This study aimed to investigate the protective role of polyphenolic extract of Euphorbia supina (PPEES) on Mn-induced neurotoxicity and the underlying mechanism in human neuroblastoma SKNMC cells and Sprague-Dawley (SD) male rat brain. PPEES possessed significant amount of total phenolic and flavonoid contents. PPEES also showed significant antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and reducing power capacity (RPC) assays. Our results showed that Mn treatment significantly reduced cell viability and increased lactate dehydrogenase (LDH) level, which was attenuated by PPEES pretreatment at 100 and 200 µg/mL. Additionally, PPEES pretreatment markedly attenuated Mn-induced antioxidant status alteration by resolving the ROS, MDA and GSH levels and SOD and CAT activities. PPEES pretreatment also significantly attenuated Mn-induced mitochondrial membrane potential (ΔΨm) and apoptosis. Meanwhile, PPEES pretreatment significantly reversed the Mn-induced alteration in the GRP78, GADD34, XBP-1, CHOP, Bcl-2, Bax and caspase-3 activities. Furthermore, administration of PPEES (100 and 200 mg/kg) to Mn exposed rats showed improvement of histopathological alteration in comparison to Mn-treated rats. Moreover, administration of PPEES to Mn exposed rats showed significant reduction of 8-OHdG and Bax immunoreactivity. The results suggest that PPEES treatment reduces Mn-induced oxidative stress and neuronal cell loss in SKNMC cells and in the rat brain. Therefore, PPEES may be considered as potential treat-ment in Mn-intoxicated patients. PMID:28146110

  14. Causal Categories: Relativistically Interacting Processes

    NASA Astrophysics Data System (ADS)

    Coecke, Bob; Lal, Raymond

    2013-04-01

    A symmetric monoidal category naturally arises as the mathematical structure that organizes physical systems, processes, and composition thereof, both sequentially and in parallel. This structure admits a purely graphical calculus. This paper is concerned with the encoding of a fixed causal structure within a symmetric monoidal category: causal dependencies will correspond to topological connectedness in the graphical language. We show that correlations, either classical or quantum, force terminality of the tensor unit. We also show that well-definedness of the concept of a global state forces the monoidal product to be only partially defined, which in turn results in a relativistic covariance theorem. Except for these assumptions, at no stage do we assume anything more than purely compositional symmetric-monoidal categorical structure. We cast these two structural results in terms of a mathematical entity, which we call a causal category. We provide methods of constructing causal categories, and we study the consequences of these methods for the general framework of categorical quantum mechanics.

  15. Learnable Classes of Categorial Grammars.

    ERIC Educational Resources Information Center

    Kanazawa, Makoto

    Learnability theory is an attempt to illuminate the concept of learnability using a mathematical model of learning. Two models of learning of categorial grammars are examined here: the standard model, in which sentences presented to the learner are flat strings of words, and one in which sentences are presented in the form of functor-argument…

  16. Category Accessibility and Impression Formation

    ERIC Educational Resources Information Center

    Higgins, E. Tory; And Others

    1977-01-01

    The present study examined the immediate and delayed effects of unobtrusive exposure to personality trait terms (e.g., "reckless,""persistent") on subjects' subsequent judgments and recollection of information about another person. The implications of individual and situational variation in the accessibility of different categories for judgments…

  17. Sentence Processing with Empty Categories.

    ERIC Educational Resources Information Center

    Gibson, Edward; Hickok, Gregory

    1993-01-01

    Pickering and Barry's recent argument against the existence of empty categories (ECs) in human sentence processing is disputed. It is argued here that ECs may still play a linking role between thematic role assigners and wh-phrases. One possible parsing algorithm is given that accounts for Pickering and Barry's data. (28 references) (Author/LB)

  18. Hurricane Irene at Category 3

    NASA Image and Video Library

    Video sequence taken by the crew of the ISS on Aug. 23, 2011 at approximately 2:15PM EST. At that time, Hurricane Irene was a Category 3 storm with peak winds estimated at 115mph, moving west-north...

  19. Mosquito and Blackfly Category Manual.

    ERIC Educational Resources Information Center

    Bowman, James S.; And Others

    This manual provides information needed to meet the standards for pesticide applicator certification. Section one is concerned with the morphology, life cycle and breeding areas of mosquitoes and the diseases resulting from their presence. The second section covers similar categories in relation to the black fly population. Calculation methods and…

  20. Grassland Assessment Categories and Extent

    Treesearch

    Wayne A. Robbie

    2004-01-01

    This chapter establishes a general framework for describing the various kinds of grasslands outlined in subsequent chapters. This framework outlines the major categories or classes of grasslands that occur as part of Southwestern terrestrial ecosystems within National Forest System lands and provides an ecological and environmental context in regards to how they differ...

  1. Linguistic Markedness and Category Learning

    ERIC Educational Resources Information Center

    Haskell, Todd R.; Mansfield, Cade D.; Brewer, Katherine M.

    2011-01-01

    Several psycholinguistic theories have appealed to the linguistic notion of markedness to help explain asymmetrical patterns of behavioural data. We suggest that this sort of markedness is best thought of as a derived rather than a primitive notion, emerging when the distributional properties of linguistic categories interact with general-purpose…

  2. Learnable Classes of Categorial Grammars.

    ERIC Educational Resources Information Center

    Kanazawa, Makoto

    Learnability theory is an attempt to illuminate the concept of learnability using a mathematical model of learning. Two models of learning of categorial grammars are examined here: the standard model, in which sentences presented to the learner are flat strings of words, and one in which sentences are presented in the form of functor-argument…

  3. Linguistic Markedness and Category Learning

    ERIC Educational Resources Information Center

    Haskell, Todd R.; Mansfield, Cade D.; Brewer, Katherine M.

    2011-01-01

    Several psycholinguistic theories have appealed to the linguistic notion of markedness to help explain asymmetrical patterns of behavioural data. We suggest that this sort of markedness is best thought of as a derived rather than a primitive notion, emerging when the distributional properties of linguistic categories interact with general-purpose…

  4. Category Accessibility and Impression Formation

    ERIC Educational Resources Information Center

    Higgins, E. Tory; And Others

    1977-01-01

    The present study examined the immediate and delayed effects of unobtrusive exposure to personality trait terms (e.g., "reckless,""persistent") on subjects' subsequent judgments and recollection of information about another person. The implications of individual and situational variation in the accessibility of different categories for judgments…

  5. Identification of Prelinguistic Phonological Categories

    PubMed Central

    Ramsdell, Heather L.; Oller, D. Kimbrough; Buder, Eugene H.; Ethington, Corinna A.; Chorna, Lesya

    2014-01-01

    Purpose The prelinguistic infant’s babbling repertoire of syllables—the phonological categories that form the basis for early word learning—is noticed by caregivers who interact with infants around them. Prior research on babbling has not explored the caregiver’s role in recognition of early vocal categories as foundations for word learning. In the present work, the authors begin to address this gap. Method The authors explored vocalizations produced by 8 infants at 3 ages (8, 10, and 12 months) in studies illustrating identification of phonological categories through caregiver report, laboratory procedures simulating the caregiver’s natural mode of listening, and the more traditional laboratory approach (phonetic transcription). Results Caregivers reported small repertoires of syllables for their infants. Repertoires of similar size and phonetic content were discerned in the laboratory by judges who simulated the caregiver’s natural mode of listening. However, phonetic transcription with repeated listening to infant recordings yielded repertoire sizes that vastly exceeded those reported by caregivers and naturalistic listeners. Conclusions The results suggest that caregiver report and naturalistic listening by laboratory staff can provide a new way to explore key characteristics of early infant vocal categories, a way that may provide insight into later speech and language development. PMID:22490623

  6. Mosquito and Blackfly Category Manual.

    ERIC Educational Resources Information Center

    Bowman, James S.; And Others

    This manual provides information needed to meet the standards for pesticide applicator certification. Section one is concerned with the morphology, life cycle and breeding areas of mosquitoes and the diseases resulting from their presence. The second section covers similar categories in relation to the black fly population. Calculation methods and…

  7. Identification of prelinguistic phonological categories.

    PubMed

    Ramsdell, Heather L; Oller, D Kimbrough; Buder, Eugene H; Ethington, Corinna A; Chorna, Lesya

    2012-12-01

    The prelinguistic infant's babbling repertoire of syllables--the phonological categories that form the basis for early word learning--is noticed by caregivers who interact with infants around them. Prior research on babbling has not explored the caregiver's role in recognition of early vocal categories as foundations for word learning. In the present work, the authors begin to address this gap. The authors explored vocalizations produced by 8 infants at 3 ages (8, 10, and 12 months) in studies illustrating identification of phonological categories through caregiver report, laboratory procedures simulating the caregiver's natural mode of listening, and the more traditional laboratory approach (phonetic transcription). Caregivers reported small repertoires of syllables for their infants. Repertoires of similar size and phonetic content were discerned in the laboratory by judges who simulated the caregiver's natural mode of listening. However, phonetic transcription with repeated listening to infant recordings yielded repertoire sizes that vastly exceeded those reported by caregivers and naturalistic listeners. The results suggest that caregiver report and naturalistic listening by laboratory staff can provide a new way to explore key characteristics of early infant vocal categories, a way that may provide insight into later speech and language development.

  8. Regulated delayed expression of rfc enhances the immunogenicity and protective efficacy of a heterologous antigen delivered by live attenuated Salmonella enterica vaccines.

    PubMed

    Kong, Qingke; Liu, Qing; Jansen, Angela M; Curtiss, Roy

    2010-08-23

    The Salmonella rfc gene encodes the O-antigen polymerase. We constructed three strains in which we replaced the native rfc promoter with the arabinose-dependent araC P(BAD) promoter so that rfc expression was dependent on exogenously supplied arabinose provided during in vitro growth. The three mutant strains were designed to synthesize different amounts of Rfc by altering the ribosome-binding sequence and start codon. We examined these strains for a number of in vitro characteristics compared to an isogenic Deltarfc mutant and the wild-type parent strain. One promoter-replacement mutation, DeltaP(rfc174), yielded an optimal profile, exhibiting wild-type characteristics when grown with arabinose, and Deltarfc characteristics when grown without arabinose. In addition, when administered orally, the DeltaP(rfc174) strain was completely attenuated in for virulence in mice. The DeltaP(rfc174) mutation was introduced into attenuated Salmonella vaccine strain chi9241 (DeltapabA DeltapabB DeltaasdA) followed by introduction of an Asd(+) balanced-lethal plasmid to designed for expression of the pneumococcal surface protein PspA. Mice immunized with either chi9241 or its DeltaP(rfc174) derivative expressing pspA were protected against S. pneumoniae challenge.

  9. The Role of Corticostriatal Systems in Speech Category Learning

    PubMed Central

    Yi, Han-Gyol; Maddox, W. Todd; Mumford, Jeanette A.; Chandrasekaran, Bharath

    2016-01-01

    One of the most difficult category learning problems for humans is learning nonnative speech categories. While feedback-based category training can enhance speech learning, the mechanisms underlying these benefits are unclear. In this functional magnetic resonance imaging study, we investigated neural and computational mechanisms underlying feedback-dependent speech category learning in adults. Positive feedback activated a large corticostriatal network including the dorsolateral prefrontal cortex, inferior parietal lobule, middle temporal gyrus, caudate, putamen, and the ventral striatum. Successful learning was contingent upon the activity of domain-general category learning systems: the fast-learning reflective system, involving the dorsolateral prefrontal cortex that develops and tests explicit rules based on the feedback content, and the slow-learning reflexive system, involving the putamen in which the stimuli are implicitly associated with category responses based on the reward value in feedback. Computational modeling of response strategies revealed significant use of reflective strategies early in training and greater use of reflexive strategies later in training. Reflexive strategy use was associated with increased activation in the putamen. Our results demonstrate a critical role for the reflexive corticostriatal learning system as a function of response strategy and proficiency during speech category learning. Keywords: category learning, fMRI, corticostriatal systems, speech, putamen PMID:25331600

  10. Optimizing rating scale category effectiveness.

    PubMed

    Linacre, John M

    2002-01-01

    Rating scales are employed as a means of extracting more information out of an item than would be obtained from a mere "yes/no", "right/wrong" or other dichotomy. But does this additional information increase measurement accuracy and precision? Eight guidelines are suggested to aid the analyst in optimizing the manner in which rating scales categories cooperate in order to improve the utility of the resultant measures. Though these guidelines are presented within the context of Rasch analysis, they reflect aspects of rating scale functioning which impact all methods of analysis. The guidelines feature rating-scale-based data such as category frequency, ordering, rating-to-measure inferential coherence, and the quality of the scale from measurement and statistical perspectives. The manner in which the guidelines prompt recategorization or reconceptualization of the rating scale is indicated. Utilization of the guidelines is illustrated through their application to two published data sets.

  11. Category Learning in the Brain

    PubMed Central

    Seger, Carol A.; Miller, Earl K.

    2013-01-01

    The ability to group items and events into functional categories is a fundamental characteristic of sophisticated thought. It is subserved by plasticity in many neural systems, including neocortical regions (sensory, prefrontal, parietal, and motor cortex), the medial temporal lobe, the basal ganglia, and midbrain dopaminergic systems. These systems interact during category learning. Corticostriatal loops may mediate recursive, bootstrapping interactions between fast reward-gated plasticity in the basal ganglia and slow reward-shaded plasticity in the cortex. This can provide a balance between acquisition of details of experiences and generalization across them. Interactions between the corticostriatal loops can integrate perceptual, response, and feedback-related aspects of the task and mediate the shift from novice to skilled performance. The basal ganglia and medial temporal lobe interact competitively or cooperatively, depending on the demands of the learning task. PMID:20572771

  12. Color Vision: Representing Material Categories

    DTIC Science & Technology

    1984-05-01

    pigniv!i an(’I ermbte(Jlmq matterial . C 2 UPul’ .AND rUCIARDS COLOR AND MATERIAL CATEGORIES 3. The Opposite Slope Sign Inference 5i. 1 The Lawf ill Ff...Part II)," Proc. Natl. Acad. Sci. USA, 45, 636- 644, 1959b. Land, E.H., "Recent advances in retinex theory and some implications for cortical computa

  13. Melatonin treatment attenuates postharvest decay and maintains nutritional quality of strawberry fruits (Fragaria×anannasa cv. Selva) by enhancing GABA shunt activity.

    PubMed

    Aghdam, Morteza Soleimani; Fard, Javad Rezapour

    2017-04-15

    Fresh strawberry fruits as perishable commodities have a short postharvest life and are prone to postharvest fungal decay. In this study, the impact of 0, 1, 10, 100 and 1000μmol/L melatonin on attenuating fungal decay and maintaining nutritional quality of strawberry fruits was investigated during storage at 4°C for 12days. Melatonin treatment at 100μmol/L triggered H2O2 accumulation, which result from higher superoxide dismutase (SOD) activity, associated with lower catalase (CAT) and ascorbate peroxidase (APX) activities, leading to fruits with lower decay. Higher H2O2 accumulation was concurrent with higher phenylalanine ammonia lyase (PAL) enzyme activity leading to higher total phenols and anthocyanins accumulation along with higher DPPH scavenging capacity. Also, strawberry fruits treated with melatonin exhibited higher γ-aminobutyric acid transaminase (GABA-T) enzyme activity which ensured sufficient ATP supplying leading to higher unsaturated/saturated fatty acids (unSFA/SFA) ratio.

  14. Rosmarinic Acid Attenuates Cell Damage against UVB Radiation-Induced Oxidative Stress via Enhancing Antioxidant Effects in Human HaCaT Cells

    PubMed Central

    Fernando, Pattage Madushan Dilhara Jayatissa; Piao, Mei Jing; Kang, Kyoung Ah; Ryu, Yea Seong; Hewage, Susara Ruwan Kumara Madduma; Chae, Sung Wook; Hyun, Jin Won

    2016-01-01

    This study was designed to investigate the cytoprotective effect of rosmarinic acid (RA) on ultraviolet B (UVB)-induced oxidative stress in HaCaT keratinocytes. RA exerted a significant cytoprotective effect by scavenging intracellular ROS induced by UVB. RA also attenuated UVB-induced oxidative macromolecular damage, including protein carbonyl content, DNA strand breaks, and the level of 8-isoprostane. Furthermore, RA increased the expression and activity of superoxide dismutase, catalase, heme oxygenase-1, and their transcription factor Nrf2, which are decreased by UVB radiation. Collectively, these data indicate that RA can provide substantial cytoprotection against the adverse effects of UVB radiation by modulating cellular antioxidant systems, and has potential to be developed as a medical agent for ROS-induced skin diseases. PMID:26759705

  15. 75 FR 40756 - Implementation Guidance for Physical Protection of Byproduct Material; Category 1 and Category 2...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-14

    ... of Byproduct Material; Category 1 and Category 2 Quantities of Radioactive Material AGENCY: Nuclear... requirements for the use and transport of category 1 and category 2 quantities of radioactive material. The NRC... category 1 and category 2 quantities of radioactive material into a new part 37 of title 10 of the Code of...

  16. 14 CFR 91.191 - Category II and Category III manual.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Category II and Category III manual. 91.191... Instrument Flight Rules § 91.191 Category II and Category III manual. (a) Except as provided in paragraph (c... Category II or a Category III operation unless— (1) There is available in the aircraft a current and...

  17. 7 CFR 993.503 - Size category.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Size category. 993.503 Section 993.503 Agriculture... Pack Specification as to Size Definitions § 993.503 Size category. Size category means each of the size categories listed in § 993.515 and fixes the range or the limits of the various size counts. Effective Date...

  18. 14 CFR 23.3 - Airplane categories.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Airplane categories. 23.3 Section 23.3... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES General § 23.3 Airplane categories. (a) The normal category is limited to airplanes that have a seating configuration, excluding...

  19. 14 CFR 23.3 - Airplane categories.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Airplane categories. 23.3 Section 23.3... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES General § 23.3 Airplane categories. (a) The normal category is limited to airplanes that have a seating configuration, excluding...

  20. 14 CFR 23.3 - Airplane categories.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Airplane categories. 23.3 Section 23.3... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES General § 23.3 Airplane categories. (a) The normal category is limited to airplanes that have a seating configuration, excluding pilot...

  1. 14 CFR 23.3 - Airplane categories.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Airplane categories. 23.3 Section 23.3... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES General § 23.3 Airplane categories. (a) The normal category is limited to airplanes that have a seating configuration, excluding pilot...

  2. Relational categories are more mutable than entity categories.

    PubMed

    Asmuth, Jennifer; Gentner, Dedre

    2017-10-01

    Across three experiments, we explore differences between relational categories-whose members share common relational patterns-and entity categories, whose members share common intrinsic properties. Specifically, we test the claim that relational concepts are more semantically mutable in context, and therefore less stable in memory, than entity concepts. We compared memory for entity nouns and relational nouns, tested either in the same context as at encoding or in a different context. We found that (a) participants show better recognition accuracy for entity nouns than for relational nouns, and (b) recognition of relational nouns is more impaired by a change in context than is recognition of entity nouns. We replicated these findings even when controlling for factors highly correlated with relationality, such as abstractness-concreteness. This suggests that the contextual mutability of relational concepts is due to the core semantic property of conveying relational structure and not simply to accompanying characteristics such as abstractness. We note parallels with the distinction between nouns and verbs and suggest implications for lexical and conceptual structure. Finally, we relate these patterns to proposals that a deep distinction exists between words with an essentially referential function and those with a predicate function.

  3. Pressure surge attenuator

    DOEpatents

    Christie, Alan M.; Snyder, Kurt I.

    1985-01-01

    A pressure surge attenuation system for pipes having a fluted region opposite crushable metal foam. As adapted for nuclear reactor vessels and heads, crushable metal foam is disposed to attenuate pressure surges.

  4. Global Attenuation Model of the Upper Mantle

    NASA Astrophysics Data System (ADS)

    Adenis, A.; Debayle, E.; Ricard, Y. R.

    2015-12-01

    We present a three-dimensional shear attenuation model based on a massive surface wave data-set (372,629 Rayleigh waveforms analysed in the period range 50-300s by Debayle and Ricard, 2012). For each seismogram, this approach yields depth-dependent path average models of shear velocity and quality factor, and a set of fundamental and higher-mode dispersion and attenuation curves. We combine these attenuation measurements in a tomographic inversion after a careful rejection of the noisy data. We first remove data likely to be biased by a poor knowledge of the source. Then we assume that waves corresponding to events having close epicenters and recorded at the same station sample the same elastic and anelastic structure, we cluster the corresponding rays and average the attenuation measurements. Logarithms of the attenuations are regionalized using the non-linear east square formalism of Tarantola and Valette (1982), resulting in attenuation tomographic maps between 50s and 300s. After a first inversion, outlyers are rejected and a second inversion yields a moderate variance reduction of about 20%. We correct the attenuation curves for focusing effect using the linearized ray theory of Woodhouse and Wong (1986). Accounting for focussing effects allows building tomographic maps with variance reductions reaching 40%. In the period range 120-200s, the root mean square of the model perturbations increases from about 5% to 20%. Our 3-D attenuation models present strong agreement with surface tectonics at period lower than 200s. Areas of low attenuation are located under continents and areas of high attenuation are associated with oceans. Surprisingly, although mid oceanic ridges are located in attenuating regions, their signature, even if enhanced by focusing corrections, remains weaker than in the shear velocity models. Synthetic tests suggests that regularisation contributes to damp the attenuation signature of ridges, which could therefore be underestimated.

  5. The Role of Corticostriatal Systems in Speech Category Learning.

    PubMed

    Yi, Han-Gyol; Maddox, W Todd; Mumford, Jeanette A; Chandrasekaran, Bharath

    2016-04-01

    One of the most difficult category learning problems for humans is learning nonnative speech categories. While feedback-based category training can enhance speech learning, the mechanisms underlying these benefits are unclear. In this functional magnetic resonance imaging study, we investigated neural and computational mechanisms underlying feedback-dependent speech category learning in adults. Positive feedback activated a large corticostriatal network including the dorsolateral prefrontal cortex, inferior parietal lobule, middle temporal gyrus, caudate, putamen, and the ventral striatum. Successful learning was contingent upon the activity of domain-general category learning systems: the fast-learning reflective system, involving the dorsolateral prefrontal cortex that develops and tests explicit rules based on the feedback content, and the slow-learning reflexive system, involving the putamen in which the stimuli are implicitly associated with category responses based on the reward value in feedback. Computational modeling of response strategies revealed significant use of reflective strategies early in training and greater use of reflexive strategies later in training. Reflexive strategy use was associated with increased activation in the putamen. Our results demonstrate a critical role for the reflexive corticostriatal learning system as a function of response strategy and proficiency during speech category learning.

  6. Resveratrol Attenuates Subacute Systemic Inflammation-Induced Spatial Memory Impairment via Inhibition of Astrocyte Activation and Enhancement of Synaptophysin Expression in the Hippocampus.

    PubMed

    Chen, Ying-Ying; Zhang, Li; Shi, Dong-Ling; Song, Xing-Hui; Shen, Yue-Liang; Zheng, Ming-Zhi; Wang, Lin-Lin

    2017-01-01

    The aim of this study was to investigate the role of resveratrol on subacute systemic inflammation-induced dysfunction of cognitive memory in mice and its underlying mechanism. Male ICR mice were trained in a water maze for four days of acquisition training and one day of probe trial. Subacute treatment with lipopolysaccharide (LPS) (1 mg/kg) by intraperitoneal injection for 5 days was used to establish a systemic inflammatory model. All mice were sacrificed after probe testing, then the expression of glial fibrillary acidic protein (GFAP), synaptophysin, and sirtuin1 (SIRT1) in hippocampi were determined using immunohistochemistry or western blot analysis. Morris water maze tests indicated that hippocampus-dependent spatial learning and memory were impaired in LPS-treated group. Resveratrol attenuated LPS-induced memory deficit in dose-dependent manner. Immunohistochemistry and western blot analysis revealed that LPS increased hippocampal GFAP expression and inhibited synaptophysin expression, which were prevented by resveratrol treatment. Treatment with LPS declined the SIRT1 protein expression in the hippocampus, which could be prevented by resveratrol. The protective effect of resveratrol could be abolished by a specific SIRT1 inhibitor. Our findings add new experimental data for potential therapeutic effects of resveratrol in the brain in a model of subacute systemic inflammation-induced astrocyte activation, synaptic alteration and cognitive decline. © 2017 by the Association of Clinical Scientists, Inc.

  7. Blockage of Autophagy in C6 Glioma Cells Enhanced Radiosensitivity Possibly by Attenuating DNA-PK-Dependent DSB Due to Limited Ku Nuclear Translocation and DNA Binding.

    PubMed

    Liu, C; He, W; Jin, M; Li, H; Xu, H; Liu, H; Yang, K; Zhang, T; Wu, G; Ren, J

    2015-01-01

    Glioblastoma multiforme (GBM) is the most lethal brain tumor and notorious for its resistance to ionizing radiation (IR). Recent evidence suggests that one possible mechanism that enables resistance to IR and protects cells against therapeutic stress is cellular autophagy. The molecular basis for this pro-survival function, however, remains elusive. Herein, we report a molecular mechanism by which IR-induced autophagy accelerates the repair of DNA double-strand breaks (DSB). We demonstrate that IR induces the accumulation of autophagosomes, which is accompanied by elevated expression of autophagyrelated genes beclin-1, atg5, atg7, and atg12. Beclin-1 knockdown impaired the induction of IR-mediated autophagy and significantly sensitized glioma cells to radiation therapy in vitro and in vivo. Furthermore, our data is the first to demonstrate that the radiosensitizing effect of beclin-1 knockdown may result from the disruption of nuclear translocation and DNA binding activity of Ku proteins and consequent attenuation of DSB repair. Our findings help advance our understanding of the molecular mechanisms underlying IR-induced autophagy and provide a promising adjunctive therapeutic strategy for the radiosensitization of malignant glioma.

  8. De-phosphorylation of translation initiation factor 2α (eIF2α) enhances glucose tolerance and attenuates hepato-steatosis in mice

    PubMed Central

    Oyadomari, Seiichi; Harding, Heather P.; Zhang, Yuhong; Oyadomari, Miho; Ron, David

    2008-01-01

    Summary The molecular mechanisms linking the stress of unfolded proteins in the endoplasmic reticulum (ER stress) to glucose intolerance in obese animals are poorly understood. In this study enforced expression of a translation initiation 2α(eIF2α)-specific phosphatase, GADD34, was used to selectively compromise signaling in the eIF2(αP)-dependent arm of the ER unfolded protein response in liver of transgenic mice. The transgene resulted in lower liver glycogen levels and susceptibility to fasting hypoglycemia in lean mice and glucose tolerance and diminished hepato-steatosis in animals fed a high fat diet. Attenuated eIF2(αP) correlated with lower expression of the adipogenic nuclear receptor PPARγ and its upstream regulators, the transcription factors C/EBPα and C/EBPβ, in transgenic mouse liver, whereas eIF2α phosphorylation promoted C/EBP translation in cultured cells and primary hepatocytes. These observations suggest that eIF2(αP)-mediated translation of key hepatic transcriptional regulators of intermediary metabolism contributes to the detrimental consequences of nutrient excess. PMID:18522833

  9. Accelerated acute allograft rejection accompanied by enhanced T-cell proliferation and attenuated Treg function in RBP-J deficient mice.

    PubMed

    Fu, Tao; Zhang, Ping; Feng, Lei; Ji, Gang; Wang, Xiao-Hong; Zheng, Min-Hua; Qin, Hong-Yan; Chen, Dong-Li; Wang, Wei-Zhong; Han, Hua

    2011-02-01

    Acute allograft rejection (AAR) involves both the innate and the adaptive immune systems. As a critical pathway in peripheral T-cell differentiation and function, Notch signaling is potentially involved in the modulation of AAR, but its role in alloimmune responses has not been fully addressed. By using fully MHC-mismatched allograft transplantation model and T-cell specific RBP-J deficient mice, we examined the role of Notch/RBP-J pathway in alloimmune responses in vivo. AAR was significantly accelerated in RBP-J deficient mice compared with the wild-type controls, as demonstrated by the marked reduction in graft survival. The reduction in graft survival was associated with augmented alloantigen specific T-cell proliferation and increased number of Th1, Th2, and Th17 cells in the RBP-J deficient recipient mice. Furthermore, although the frequency of CD4(+)CD25(+)Foxp3(+) Tregs was intact in RBP-J knockout recipients, their ability to suppress Teff responses in vitro was significantly dampened. These findings suggest that Notch/RBP-J pathway may attenuate AAR by suppressing in vivo expansion of alloreactive T-cell proliferation and facilitating CD4(+)CD25(+) Treg suppression ability, indicating that Notch pathway could be exploited to limit T-cell-mediated AAR. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Enhanced motivation for food reward induced by stress and attenuation by corticotrophin-releasing factor receptor antagonism in rats: implications for overeating and obesity.

    PubMed

    Liu, Xiu

    2015-06-01

    Overeating beyond individuals' homeostatic needs critically contributes to obesity. The neurobehavioral mechanisms underlying the motivation to consume excessive foods with high calories are not fully understood. The present study examined whether a pharmacological stressor, yohimbine, enhances the motivation to procure food reward with an emphasis on comparisons between standard lab chow and high-fat foods. The effects of corticotropin-releasing factor (CRF) receptor blockade by a CRF1-selective antagonist NBI on the stress-enhanced motivation for food reward were also assessed. Male Sprague-Dawley rats with chow available ad libitum in their home cages were trained to press a lever under a progressive ratio schedule for deliveries of either standard or high-fat food pellets. For testing yohimbine stress effects, rats received an intraperitoneal administration of yohimbine 10 min before start of the test sessions. For testing effects of CRF1 receptor blockade on stress responses, NBI was administered 20 min prior to yohimbine challenge. The rats emitted higher levels of lever responses to procure the high-fat food pellets compared with their counterparts on standard food pellets. Yohimbine challenge facilitated lever responses for the reward in all of the rats, whereas the effect was more robust in the rats on high-fat food pellets compared with their counterparts on standard food pellets. An inhibitory effect of pretreatment with NBI was observed on the enhancing effect of yohimbine challenge but not on the responses under baseline condition without yohimbine administration. Stress challenge significantly enhanced the motivation of satiated rats to procure extra food reward, especially the high-fat food pellets. Activation of CRF1 receptors is required for the stress-enhanced motivation for food reward. These results may have implications for our better understanding of the biobehavioral mechanisms of overeating and obesity.

  11. Enhanced motivation for food reward induced by stress and attenuation by corticotrophin-releasing factor receptor antagonism in rats: implications for overeating and obesity

    PubMed Central

    Liu, Xiu

    2014-01-01

    Rationale Overeating beyond individuals’ homeostatic needs critically contributes to obesity. The neurobehavioral mechanisms underlying the motivation to consume excessive foods with high calories are not fully understood. Objective The present study examined whether a pharmacological stressor, yohimbine enhances the motivation to procure food reward with an emphasis on comparisons between standard lab chow and high-fat foods. The effects of corticotropin-releasing factor receptor (CRF1) blockade by a CFR1 selective antagonist NBI on the stress-enhanced motivation for food reward were also assessed. Methods Male Sprague-Dawley rats with chow available ad libitum in their home cages were trained to press a lever under a progressive-ratio schedule for deliveries of either standard or high-fat food pellets. For testing yohimbine stress effects, rats received an intraperitoneal administration of yohimbine 10 min before start of the test sessions. For testing effects of CRF1 receptor blockade on stress responses, NBI was administered 20 min prior to yohimbine challenge. Results The rats emitted higher levels of lever responses to procure the high-fat food pellets compared with their counterparts on standard food pellets. Yohimbine challenge facilitated lever responses for the reward in all of the rats, whereas the effect was more robust in the rats on high-fat food pellets compared with their counterparts on standard food pellets. An inhibitory effect of pretreatment with NBI was observed on the enhancing effect of yohimbine challenge but not on the responses under baseline condition without yohimbine administration. Conclusions Stress challenge significantly enhanced the motivation of satiated rats to procure extra food reward, especially the high-fat food pellets. Activation of CRF1 receptors is required for the stress-enhanced motivation for food reward. These results may have implications for our better understanding of the biobehavioral mechanisms of overeating

  12. Tracer attenuation in groundwater

    NASA Astrophysics Data System (ADS)

    Cvetkovic, Vladimir

    2011-12-01

    The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

  13. Feasibility of simultaneous whole-brain imaging on an integrated PET-MRI system using an enhanced 2-point Dixon attenuation correction method

    PubMed Central

    Anazodo, Udunna C.; Thiessen, Jonathan D.; Ssali, Tracy; Mandel, Jonathan; Günther, Matthias; Butler, John; Pavlosky, William; Prato, Frank S.; Thompson, R. Terry; St. Lawrence, Keith S.

    2015-01-01

    Purpose: To evaluate a potential approach for improved attenuation correction (AC) of PET in simultaneous PET and MRI brain imaging, a straightforward approach that adds bone information missing on Dixon AC was explored. Methods: Bone information derived from individual T1-weighted MRI data using segmentation tools in SPM8, were added to the standard Dixon AC map. Percent relative difference between PET reconstructed with Dixon+bone and with Dixon AC maps were compared across brain regions of 13 oncology patients. The clinical potential of the improved Dixon AC was investigated by comparing relative perfusion (rCBF) measured with arterial spin labeling to relative glucose uptake (rPETdxbone) measured simultaneously with 18F-flurodexoyglucose in several regions across the brain. Results: A gradual increase in PET signal from center to the edge of the brain was observed in PET reconstructed with Dixon+bone. A 5–20% reduction in regional PET signals were observed in data corrected with standard Dixon AC maps. These regional underestimations of PET were either reduced or removed when Dixon+bone AC was applied. The mean relative correlation coefficient between rCBF and rPETdxbone was r = 0.53 (p < 0.001). Marked regional variations in rCBF-to-rPET correlation were observed, with the highest associations in the caudate and cingulate and the lowest in limbic structures. All findings were well matched to observations from previous studies conducted with PET data reconstructed with computed tomography derived AC maps. Conclusion: Adding bone information derived from T1-weighted MRI to Dixon AC maps can improve underestimation of PET activity in hybrid PET-MRI neuroimaging. PMID:25601825

  14. CTLA-4 blockade enhances the therapeutic effect of an attenuated poxvirus vaccine targeting p53 in an established murine tumor model.

    PubMed

    Espenschied, Jonathan; Lamont, Jeffrey; Longmate, Jeff; Pendas, Solange; Wang, Zhongde; Diamond, Don J; Ellenhorn, Joshua D I

    2003-03-15

    p53 is overexpressed by half of all cancers, and is an attractive target for a vaccine approach to immunotherapy. p53 overexpression is frequently the result of point mutations, which leaves the majority of the protein in its wild-type form. Therefore, the majority of p53 sequence is wild type, making it a self-protein for which tolerance plays a role in limiting immune responses. To overcome tolerance to p53, we have expressed wild-type murine p53 in the nonpathogenic attenuated poxvirus, modified vaccinia virus Ankara (recombinant modified vaccinia virus Ankara expressing wild-type murine p53 (rMVAp53)). Mice immunized with rMVAp53 vaccine developed vigorous p53-specific CTL responses. rMVAp53 vaccine was evaluated for its ability to inhibit the outgrowth of the syngeneic murine sarcoma Meth A, which overexpresses mutant p53. Mice were inoculated with a lethal dose (5 x 10(5) cells injected s.c.) of Meth A tumor cells and vaccinated by i.p. injection 3 days later with 5 x 10(7) PFU of rMVAp53. The majority of mice remained tumor free and resistant to rechallenge with Meth A tumor cells. We wished to determine whether rMVAp53 immunization could effect the rejection of an established, palpable Meth A tumor. In subsequent experiments, mice were injected with 10(6) Meth A tumor cells, and treated 6 days later with anti-CTLA-4 Ab (9H10) and rMVAp53. The majority of treated mice had complete tumor regression along with lasting tumor immunity. In vivo Ab depletion confirmed that the antitumor effect was primarily CD8 and to a lesser extent CD4 dependent. These experiments demonstrate the potential of a novel cell-free vaccine targeting p53 in malignancy.

  15. Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis: attenuated by KYNA derivate (SZR72).

    PubMed

    Lukács, M; Warfvinge, K; Tajti, J; Fülöp, F; Toldi, J; Vécsei, L; Edvinsson, L

    2017-12-01

    Migraine is a debilitating neurological disorder where trigeminovascular activation plays a key role. We have previously reported that local application of Complete Freund's Adjuvant (CFA) onto the dura mater caused activation in rat trigeminal ganglion (TG) which was abolished by a systemic administration of kynurenic acid (KYNA) derivate (SZR72). Here, we hypothesize that this activation may extend to the trigeminal complex in the brainstem and is attenuated by treatment with SZR72. Activation in the trigeminal nucleus caudalis (TNC) and the trigeminal tract (Sp5) was achieved by application of CFA onto the dural parietal surface. SZR72 was given intraperitoneally (i.p.), one dose prior CFA deposition and repeatedly daily for 7 days. Immunohistochemical studies were performed for mapping glutamate, c-fos, PACAP, substance P, IL-6, IL-1β and TNFα in the TNC/Sp5 and other regions of the brainstem and at the C1-C2 regions of the spinal cord. We found that CFA increased c-fos and glutamate immunoreactivity in TNC and C1-C2 neurons. This effect was mitigated by SZR72. PACAP positive fibers were detected in the fasciculus cuneatus and gracilis. Substance P, TNFα, IL-6 and IL-1β immunopositivity were detected in fibers of Sp5 and neither of these molecules showed any change in immunoreactivity following CFA administration. This is the first study demonstrating that dural application of CFA increases the expression of c-fos and glutamate in TNC neurons. Treatment with the KYNA analogue prevented this expression.

  16. Nanowired Delivery of Growth Hormone Attenuates Pathophysiology of Spinal Cord Injury and Enhances Insulin-Like Growth Factor-1 Concentration in the Plasma and the Spinal Cord.

    PubMed

    Muresanu, Dafin F; Sharma, Aruna; Lafuente, José V; Patnaik, Ranjana; Tian, Z Ryan; Nyberg, Fred; Sharma, Hari S

    2015-10-01

    Previous studies from our laboratory showed that topical application of growth hormone (GH) induced neuroprotection 5 h after spinal cord injury (SCI) in a rat model. Since nanodelivery of drugs exerts superior neuroprotective effects, a possibility exists that nanodelivery of GH will induce long-term neuroprotection after a focal SCI. SCI induces GH deficiency that is coupled with insulin-like growth factor-1 (IGF-1) reduction in the plasma. Thus, an exogenous supplement of GH in SCI may enhance the IGF-1 levels in the cord and induce neuroprotection. In the present investigation, we delivered TiO2-nanowired growth hormone (NWGH) after a longitudinal incision of the right dorsal horn at the T10-11 segments in anesthetized rats and compared the results with normal GH therapy on IGF-1 and GH contents in the plasma and in the cord in relation to blood-spinal cord barrier (BSCB) disruption, edema formation, and neuronal injuries. Our results showed a progressive decline in IGF-1 and GH contents in the plasma and the T9 and T12 segments of the cord 12 and 24 h after SCI. Marked increase in the BSCB breakdown, as revealed by extravasation of Evans blue and radioiodine, was seen at these time points after SCI in association with edema and neuronal injuries. Administration of NWGH markedly enhanced the IGF-1 levels and GH contents in plasma and cord after SCI, whereas normal GH was unable to enhance IGF-1 or GH levels 12 or 24 h after SCI. Interestingly, NWGH was also able to reduce BSCB disruption, edema formation, and neuronal injuries after trauma. On the other hand, normal GH was ineffective on these parameters at all time points examined. Taken together, our results are the first to demonstrate that NWGH is quite effective in enhancing IGF-1 and GH levels in the cord and plasma that may be crucial in reducing pathophysiology of SCI.

  17. PPARγ-induced Upregulation of CD36 Enhances Hematoma Resolution and Attenuates Long-term Neurological Deficits after Germinal Matrix Hemorrhage in Neonatal Rats

    PubMed Central

    Flores, Jerry J.; Klebe, Damon; Rolland, William B.; Lekic, Tim; Krafft, Paul R.; Zhang, John H.

    2016-01-01

    Germinal matrix hemorrhage remains the leading cause of morbidity and mortality in preterm infants in the United States with little progress made in its clinical management. Survivors are often afflicted with long-term neurological sequelae, including cerebral palsy, mental retardation, hydrocephalus, and psychiatric disorders. Blood clots disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage are thought to be important contributors towards post-hemorrhagic hydrocephalus development. We evaluated if upregulating CD36 scavenger receptor expression in microglia and macrophages through PPARγ stimulation, which was effective in experimental adult cerebral hemorrhage models and is being evaluated clinically, will enhance hematoma resolution and ameliorate long-term brain sequelae using a neonatal rat germinal matrix hemorrhage model. PPARγ stimulation (15d-PGJ2) increased short-term PPARγ and CD36 expression levels as well as enhanced hematoma resolution, which was reversed by a PPARγ antagonist (GW9662) and CD36 siRNA. PPARγ stimulation (15d-PGJ2) also reduced long-term white matter loss and post-hemorrhagic ventricular dilation as well as improved neurofunctional outcomes, which were reversed by a PPARγ antagonist (GW9662). PPARγ-induced upregulation of CD36 in macrophages and microglia is, therefore, critical for enhancing hematoma resolution and ameliorating long-term brain sequelae. PMID:26739391

  18. PPARγ-induced upregulation of CD36 enhances hematoma resolution and attenuates long-term neurological deficits after germinal matrix hemorrhage in neonatal rats.

    PubMed

    Flores, Jerry J; Klebe, Damon; Rolland, William B; Lekic, Tim; Krafft, Paul R; Zhang, John H

    2016-03-01

    Germinal matrix hemorrhage remains the leading cause of morbidity and mortality in preterm infants in the United States with little progress made in its clinical management. Survivors are often afflicted with long-term neurological sequelae, including cerebral palsy, mental retardation, hydrocephalus, and psychiatric disorders. Blood clots disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage are thought to be important contributors towards post-hemorrhagic hydrocephalus development. We evaluated if upregulating CD36 scavenger receptor expression in microglia and macrophages through PPARγ stimulation, which was effective in experimental adult cerebral hemorrhage models and is being evaluated clinically, will enhance hematoma resolution and ameliorate long-term brain sequelae using a neonatal rat germinal matrix hemorrhage model. PPARγ stimulation (15d-PGJ2) increased short-term PPARγ and CD36 expression levels as well as enhanced hematoma resolution, which was reversed by a PPARγ antagonist (GW9662) and CD36 siRNA. PPARγ stimulation (15d-PGJ2) also reduced long-term white matter loss and post-hemorrhagic ventricular dilation as well as improved neurofunctional outcomes, which were reversed by a PPARγ antagonist (GW9662). PPARγ-induced upregulation of CD36 in macrophages and microglia is, therefore, critical for enhancing hematoma resolution and ameliorating long-term brain sequelae.

  19. The history of psychological categories.

    PubMed

    Smith, Roger

    2005-03-01

    Psychological terms, such as 'mind', 'memory', 'emotion' and indeed 'psychology' itself, have a history. This history, I argue, supports the view that basic psychological categories refer to historical and social entities, and not to 'natural kinds'. The case is argued through a wide ranging review of the historiography of western psychology, first, in connection with the field's extreme modern diversity; second, in relation to the possible antecedents of the field in the early modern period; and lastly, through a brief introduction to usage of the words 'soul', 'mind', 'memory' and 'emotion'. The discussion situates the history of psychology within a large historical context, questions assumptions about the continuity of meaning, and draws out implications for the philosophical and social constitution of 'psychology' and 'the psychological' from the existing literature. The historical evidence, this paper concludes, does not support the conventional presumption that modern psychological terms describe 'natural kinds'.

  20. Within-Category Discontinuity Interacts with Verbal Rule Complexity in Perceptual Category Learning

    ERIC Educational Resources Information Center

    Maddox, W. Todd; Filoteo, J. Vincent; Lauritzen, J. Scott

    2007-01-01

    A test of the predicted interaction between within-category discontinuity and verbal rule complexity on information-integration and rule-based category learning was conducted. Within-category discontinuity adversely affected information-integration category learning but not rule-based category learning. Model-based analyses suggested that some…

  1. 75 FR 47494 - Implementation Guidance for Physical Protection of Byproduct Material; Category 1 and Category 2...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ...; Category 1 and Category 2 Quantities of Radioactive Material; Meeting AGENCY: Nuclear Regulatory Commission... category 2 quantities of radioactive material. The NRC has prepared draft guidance to address..., specifically Category 1 and Category 2 quantities of radioactive material. It is intended for use by applicants...

  2. High glutamate attenuates S100B and LDH outputs from rat cortical slices enhanced by either oxygen-glucose deprivation or menadione.

    PubMed

    Demircan, Celaleddin; Gül, Zülfiye; Büyükuysal, R Levent

    2014-07-01

    One hour incubation of rat cortical slices in a medium without oxygen and glucose (oxygen-glucose deprivation, OGD) increased S100B release to 6.53 ± 0.3 ng/ml/mg protein from its control value of 3.61 ± 0.2 ng/ml/mg protein. When these slices were then transferred to a medium containing oxygen and glucose (reoxygenation, REO), S100B release rose to 344 % of its control value. REO also caused 192 % increase in lactate dehydrogenase (LDH) leakage. Glutamate added at millimolar concentration into the medium decreased OGD or REO-induced S100B release and REO-induced LDH leakage. Alpha-ketoglutarate, a metabolic product of glutamate, was found to be as effective as glutamate in decreasing the S100B and LDH outputs. Similarly lactate, 2-ketobutyrate and ethyl pyruvate, a lipophilic derivative of pyruvate, also exerted a glutamate-like effect on S100B and LDH outputs. Preincubation with menadione, which produces H2O2 intracellularly, significantly increased S100B and LDH levels in normoxic medium. All drugs tested in the present study, with the exception of pyruvate, showed a complete protection against menadione preincubation. Additionally, each OGD-REO, menadione or H2O2-induced mitochondrial energy impairments determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining and OGD-REO or menadione-induced increases in reactive oxygen substances (ROS) determined by 2,7-dichlorofluorescin diacetate (DCFH-DA) were also recovered by glutamate. Interestingly, H2O2-induced increase in fluorescence intensity derived from DCFH-DA in a slice-free physiological medium was attenuated significantly by glutamate and alpha-keto acids. All these drug actions support the conclusion that high glutamate, such as alpha-ketoglutarate and other keto acids, protects the slices against OGD- and REO-induced S100B and LDH outputs probably by scavenging ROS in addition to its energy substrate metabolite property.

  3. Activation of KCNN3/SK3/K(Ca)2.3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia.

    PubMed

    Dolga, Amalia M; Letsche, Till; Gold, Maike; Doti, Nunzianna; Bacher, Michael; Chiamvimonvat, Nipavan; Dodel, Richard; Culmsee, Carsten

    2012-12-01

    In neurons, small-conductance calcium-activated potassium (KCNN/SK/K(Ca)2) channels maintain calcium homeostasis after N-methyl-D-aspartate (NMDA) receptor activation, thereby preventing excitotoxic neuronal death. So far, little is known about the function of KCNN/SK/K(Ca)2 channels in non-neuronal cells, such as microglial cells. In this study, we addressed the question whether KCNN/SK/K(Ca)2 channels activation affected inflammatory responses of primary mouse microglial cells upon lipopolysaccharide (LPS) stimulation. We found that N-cyclohexyl-N-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4-pyrimidinamine (CyPPA), a positive pharmacological activator of KCNN/SK/K(Ca)2 channels, significantly reduced LPS-stimulated activation of microglia in a concentration-dependent manner. The general KCNN/SK/K(Ca)2 channel blocker apamin reverted these effects of CyPPA on microglial proliferation. Since calcium plays a central role in microglial activation, we further addressed whether KCNN/SK/K(Ca)2 channel activation affected the changes of intracellular calcium levels, [Ca(2+)](i), in microglial cells. Our data show that LPS-induced elevation of [Ca(2+)](i) was attenuated following activation of KCNN2/3/K(Ca)2.2/K(Ca)2.3 channels by CyPPA. Furthermore, CyPPA reduced downstream events including tumor necrosis factor alpha and interleukin 6 cytokine production and nitric oxide release in activated microglia. Further, we applied specific peptide inhibitors of the KCNN/SK/K(Ca)2 channel subtypes to identify which particular channel subtype mediated the observed anti-inflammatory effects. Only inhibitory peptides targeting KCNN3/SK3/K(Ca)2.3 channels, but not KCNN2/SK2/K(Ca)2.2 channel inhibition, reversed the CyPPA-effects on LPS-induced microglial proliferation. These findings revealed that KCNN3/SK3/K(Ca)2.3 channels can modulate the LPS-induced inflammatory responses in microglial cells. Thus, KCNN3/SK3/K(Ca)2.3 channels may serve as a therapeutic target for reducing microglial

  4. The let-7 microRNA enhances heme oxygenase-1 by suppressing Bach1 and attenuates oxidant injury in human hepatocytes.

    PubMed

    Hou, Weihong; Tian, Qing; Steuerwald, Nury M; Schrum, Laura W; Bonkovsky, Herbert L

    2012-01-01

    The let-7 microRNA (miRNA) plays important roles in human liver development and diseases such as hepatocellular carcinoma, liver fibrosis and hepatitis wherein oxidative stress accelerates the progression of these diseases. To date, the role of the let-7 miRNA family in modulation of heme oxygenase 1 (HMOX1), a key cytoprotective enzyme, remains unknown. Our aims were to determine whether let-7 miRNA directly regulates Bach1, a transcriptional repressor of the HMOX1 gene, and whether indirect up-regulation of HMOX1 by let-7 miRNA attenuates oxidant injury in human hepatocytes. The effects of let-7 miRNA on Bach1 and HMOX1 gene expression in Huh-7 and HepG2 cells were determined by real-time qRT-PCR, Western blot, and luciferase reporter assays. Dual luciferase reporter assays revealed that let-7b, let-7c, or miR-98 significantly decreased Bach1 3'-untranslated region (3'-UTR)-dependent luciferase activity but not mutant Bach1 3'-UTR-dependent luciferase activity, whereas mutant let-7 miRNA containing base complementarity with mutant Bach1 3'-UTR restored its effect on mutant reporter activity. let-7b, let-7c, or miR-98 down-regulated Bach1 protein levels by 50-70%, and subsequently up-regulated HMOX1 gene expression by 3-4 fold, compared with non-specific controls. Furthermore, Huh-7 cells transfected with let-7b, let-7c or miR-98 mimic showed increased resistance against oxidant injury induced by tert-butyl-hydroperoxide (tBuOOH), whereas the protection was abrogated by over-expression of Bach1. In conclusion, let-7 miRNA directly acts on the 3'-UTR of Bach1 and negatively regulates expression of this protein, and thereby up-regulates HMOX1 gene expression. Over-expression of the let-7 miRNA family members may represent a novel approach to protecting human hepatocytes from oxidant injury.

  5. CYP2J2 and its metabolites (epoxyeicosatrienoic acids) attenuate cardiac hypertrophy by activating AMPKα2 and enhancing nuclear translocation of Akt1.

    PubMed

    Wang, Bei; Zeng, Hesong; Wen, Zheng; Chen, Chen; Wang, Dao Wen

    2016-10-01

    Cytochrome P450 epoyxgenase 2J2 and epoxyeicosatrienoic acids (EETs) are known to protect against cardiac hypertrophy and heart failure, which involve the activation of 5'-AMP-activated protein kinase (AMPK) and Akt. Although the functional roles of AMPK and Akt are well established, the significance of cross talk between them in the development of cardiac hypertrophy and antihypertrophy of CYP2J2 and EETs remains unclear. We investigated whether CYP2J2 and its metabolites EETs protected against cardiac hypertrophy by activating AMPKα2 and Akt1. Moreover, we tested whether EETs enhanced cross talk between AMPKα2 and phosphorylated Akt1 (p-Akt1), and stimulated nuclear translocation of p-Akt1, to exert their antihypertrophic effects. AMPKα2(-/-) mice that overexpressed CYP2J2 in heart were treated with Ang II for 2 weeks. Interestingly, overexpression of CYP2J2 suppressed cardiac hypertrophy and increased levels of atrial natriuretic peptide (ANP) in the heart tissue and plasma of wild-type mice but not AMPKα2(-/-) mice. The CYP2J2 metabolites, 11,12-EET, activated AMPKα2 to induce nuclear translocation of p-Akt1 selectively, which increased the production of ANP and therefore inhibited the development of cardiac hypertrophy. Furthermore, by co-immunoprecipitation analysis, we found that AMPKα2β2γ1 and p-Akt1 interact through the direct binding of the AMPKγ1 subunit to the Akt1 protein kinase domain. This interaction was enhanced by 11,12-EET. Our studies reveal a novel mechanism in which CYP2J2 and EETs enhanced Akt1 nuclear translocation through interaction with AMPKα2β2γ1 and protect against cardiac hypertrophy and suggest that overexpression of CYP2J2 might have clinical potential to suppress cardiac hypertrophy and heart failure. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  6. Bioconjugated Manganese Dioxide Nanoparticles Enhance Chemotherapy Response by Priming Tumor-Associated Macrophages toward M1-like Phenotype and Attenuating Tumor Hypoxia

    PubMed Central

    Shi, Changrong; Zhang, Xiangzhong; Chen, Xiaoyuan

    2017-01-01

    Hypoxia promotes not only the invasiveness of tumor cells, but also chemoresistance in cancer. Tumor associated macrophages (TAMs) residing at the site of hypoxic region of tumors have been known to cooperate with tumor cells, and promote proliferation and chemoresistance. Therefore, there is an urgent need for new strategies to alleviate tumor hypoxia and enhance chemotherapy response in solid tumors. Herein, we have taken advantage of high accumulation of TAMs in hypoxic regions of tumor and high reactivity of manganese dioxide nanoparticles (MnO2 NPs) toward hydrogen peroxide (H2O2) for the simultaneous production of O2 and regulation of pH to effectively alleviate tumor hypoxia by targeted delivery of MnO2 NPs to the hypoxic area. Furthermore, we also utilized the ability of hyaluronic acid (HA) modification in reprogramming anti-inflammatory, pro-tumoral M2 TAMs to pro-inflammatory, antitumor M1 macrophages to further enhance the ability of MnO2 NPs to lessen tumor hypoxia and modulate chemoresistance. The HA-coated, mannanconjugated MnO2 particle (Man-HA-MnO2) treatment significantly increased tumor oxygenation and down-regulated hypoxia-inducible factor-1 α (HIF-1α) and vascular endothelial growth factor (VEGF) in the tumor. Combination treatment of the tumors with Man-HA-MnO2 NPs and doxorubicin significantly increased apparent diffusion coefficient (ADC) values of breast tumor, inhibited tumor growth and tumor cell proliferation as compared with chemotherapy alone. In addition, the reaction of Man-HA-MnO2 NPs toward endogenous H2O2 highly enhanced T1- and T2-MRI performance for tumor imaging and detection. PMID:26650065

  7. HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter

    PubMed Central

    Visser, Mijke; Kayser, Manfred; Palstra, Robert-Jan

    2012-01-01

    Pigmentation of skin, eye, and hair reflects some of the most evident common phenotypes in humans. Several candidate genes for human pigmentation are identified. The SNP rs12913832 has strong statistical association with human pigmentation. It is located within an intron of the nonpigment gene HERC2, 21 kb upstream of the pigment gene OCA2, and the region surrounding rs12913832 is highly conserved among animal species. However, the exact functional role of HERC2 rs12913832 in human pigmentation is unknown. Here we demonstrate that the HERC2 rs12913832 region functions as an enhancer regulating OCA2 transcription. In darkly pigmented human melanocytes carrying the rs12913832 T-allele, we detected binding of the transcription factors HLTF, LEF1, and MITF to the HERC2 rs12913832 enhancer, and a long-range chromatin loop between this enhancer and the OCA2 promoter that leads to elevated OCA2 expression. In contrast, in lightly pigmented melanocytes carrying the rs12913832 C-allele, chromatin-loop formation, transcription factor recruitment, and OCA2 expression are all reduced. Hence, we demonstrate that allelic variation of a common noncoding SNP located in a distal regulatory element not only disrupts the regulatory potential of this element but also affects its interaction with the relevant promoter. We provide the key mechanistic insight that allele-dependent differences in chromatin-loop formation (i.e., structural differences in the folding of gene loci) result in differences in allelic gene expression that affects common phenotypic traits. This concept is highly relevant for future studies aiming to unveil the functional basis of genetically determined phenotypes, including diseases. PMID:22234890

  8. HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter.

    PubMed

    Visser, Mijke; Kayser, Manfred; Palstra, Robert-Jan

    2012-03-01

    Pigmentation of skin, eye, and hair reflects some of the most evident common phenotypes in humans. Several candidate genes for human pigmentation are identified. The SNP rs12913832 has strong statistical association with human pigmentation. It is located within an intron of the nonpigment gene HERC2, 21 kb upstream of the pigment gene OCA2, and the region surrounding rs12913832 is highly conserved among animal species. However, the exact functional role of HERC2 rs12913832 in human pigmentation is unknown. Here we demonstrate that the HERC2 rs12913832 region functions as an enhancer regulating OCA2 transcription. In darkly pigmented human melanocytes carrying the rs12913832 T-allele, we detected binding of the transcription factors HLTF, LEF1, and MITF to the HERC2 rs12913832 enhancer, and a long-range chromatin loop between this enhancer and the OCA2 promoter that leads to elevated OCA2 expression. In contrast, in lightly pigmented melanocytes carrying the rs12913832 C-allele, chromatin-loop formation, transcription factor recruitment, and OCA2 expression are all reduced. Hence, we demonstrate that allelic variation of a common noncoding SNP located in a distal regulatory element not only disrupts the regulatory potential of this element but also affects its interaction with the relevant promoter. We provide the key mechanistic insight that allele-dependent differences in chromatin-loop formation (i.e., structural differences in the folding of gene loci) result in differences in allelic gene expression that affects common phenotypic traits. This concept is highly relevant for future studies aiming to unveil the functional basis of genetically determined phenotypes, including diseases.

  9. Oral administration of Lactobacillus paracasei L9 attenuates PM2.5-induced enhancement of airway hyperresponsiveness and allergic airway response in murine model of asthma.

    PubMed

    Wang, Xifan; Hui, Yan; Zhao, Liang; Hao, Yanling; Guo, Huiyuan; Ren, Fazheng

    2017-01-01

    This study investigated allergy immunotherapy potential of Lactobacillus paracasei L9 to prevent or mitigate the particulate matter 2.5 (PM2.5) enhanced pre-existing asthma in mice. Firstly, we used a mouse model of asthma (a 21-day ovalbumin (OVA) sensitization and challenge model) followed by PM2.5 exposure twice on the same day of the last challenge. PM2.5 was collected from the urban area of Beijing and underwent analysis for metals and polycyclic aromatic hydrocarbon contents. The results showed that PM2.5 exposure enhanced airway hyper-responsiveness (AHR) and lead to a mixed Th2/ IL-17 response in asthmatic mice. Secondly, the PM2.5 exposed asthmatic mice were orally administered with L9 (4×107, 4×109 CFU/mouse, day) from the day of first sensitization to the endpoint, for 20 days, to investigate the potential mitigative effect of L9 on asthma. The results showed that L9 ameliorated PM2.5 exposure enhanced AHR with an approximate 50% decrease in total airway resistance response to methacholine (48 mg/ml). L9 also prevented the exacerbated eosinophil and neutrophil infiltration in bronchoalveolar lavage fluid (BALF), and decreased the serum level of total IgE and OVA-specific IgG1 by 0.44-fold and 0.3-fold, respectively. Additionally, cytokine production showed that L9 significantly decreased T-helper cell type 2 (Th2)-related cytokines (IL-4, -5, -13) and elevated levels of Th1 related IFN-γ in BALF. L9 also reduced the level of IL-17A and increased the level of TGF-β. Taken together, these results indicate that L9 may exert the anti-allergic benefit, possibly through rebalancing Th1/Th2 immune response and modulating IL-17 pro-inflammatory immune response. Thus, L9 is a promising candidate for preventing PM exposure enhanced pre-existing asthma.

  10. Oral administration of Lactobacillus paracasei L9 attenuates PM2.5-induced enhancement of airway hyperresponsiveness and allergic airway response in murine model of asthma

    PubMed Central

    Zhao, Liang; Hao, Yanling; Guo, Huiyuan; Ren, Fazheng

    2017-01-01

    This study investigated allergy immunotherapy potential of Lactobacillus paracasei L9 to prevent or mitigate the particulate matter 2.5 (PM2.5) enhanced pre-existing asthma in mice. Firstly, we used a mouse model of asthma (a 21-day ovalbumin (OVA) sensitization and challenge model) followed by PM2.5 exposure twice on the same day of the last challenge. PM2.5 was collected from the urban area of Beijing and underwent analysis for metals and polycyclic aromatic hydrocarbon contents. The results showed that PM2.5 exposure enhanced airway hyper-responsiveness (AHR) and lead to a mixed Th2/ IL-17 response in asthmatic mice. Secondly, the PM2.5 exposed asthmatic mice were orally administered with L9 (4×107, 4×109 CFU/mouse, day) from the day of first sensitization to the endpoint, for 20 days, to investigate the potential mitigative effect of L9 on asthma. The results showed that L9 ameliorated PM2.5 exposure enhanced AHR with an approximate 50% decrease in total airway resistance response to methacholine (48 mg/ml). L9 also prevented the exacerbated eosinophil and neutrophil infiltration in bronchoalveolar lavage fluid (BALF), and decreased the serum level of total IgE and OVA-specific IgG1 by 0.44-fold and 0.3-fold, respectively. Additionally, cytokine production showed that L9 significantly decreased T-helper cell type 2 (Th2)–related cytokines (IL-4, -5, -13) and elevated levels of Th1 related IFN-γ in BALF. L9 also reduced the level of IL-17A and increased the level of TGF-β. Taken together, these results indicate that L9 may exert the anti-allergic benefit, possibly through rebalancing Th1/Th2 immune response and modulating IL-17 pro-inflammatory immune response. Thus, L9 is a promising candidate for preventing PM exposure enhanced pre-existing asthma. PMID:28199353

  11. Effect of explicit dimension instruction on speech category learning

    PubMed Central

    Chandrasekaran, Bharath; Yi, Han-Gyol; Smayda, Kirsten E.; Maddox, W. Todd

    2015-01-01

    Learning non-native speech categories is often considered a challenging task in adulthood. This difficulty is driven by cross-language differences in weighting critical auditory dimensions that differentiate speech categories. For example, previous studies have shown that differentiating Mandarin tonal categories requires attending to dimensions related to pitch height and direction. Relative to native speakers of Mandarin, the pitch direction dimension is under-weighted by native English speakers. In the current study, we examined the effect of explicit instructions (dimension instruction) on native English speakers' Mandarin tone category learning within the framework of a dual-learning systems (DLS) model. This model predicts that successful speech category learning is initially mediated by an explicit, reflective learning system that frequently utilizes unidimensional rules, with an eventual switch to a more implicit, reflexive learning system that utilizes multidimensional rules. Participants were explicitly instructed to focus and/or ignore the pitch height dimension, the pitch direction dimension, or were given no explicit prime. Our results show that instruction instructing participants to focus on pitch direction, and instruction diverting attention away from pitch height resulted in enhanced tone categorization. Computational modeling of participant responses suggested that instruction related to pitch direction led to faster and more frequent use of multidimensional reflexive strategies, and enhanced perceptual selectivity along the previously underweighted pitch direction dimension. PMID:26542400

  12. Effect of explicit dimensional instruction on speech category learning.

    PubMed

    Chandrasekaran, Bharath; Yi, Han-Gyol; Smayda, Kirsten E; Maddox, W Todd

    2016-02-01

    Learning nonnative speech categories is often considered a challenging task in adulthood. This difficulty is driven by cross-language differences in weighting critical auditory dimensions that differentiate speech categories. For example, previous studies have shown that differentiating Mandarin tonal categories requires attending to dimensions related to pitch height and direction. Relative to native speakers of Mandarin, the pitch direction dimension is underweighted by native English speakers. In the current study, we examined the effect of explicit instructions (dimension instruction) on native English speakers' Mandarin tone category learning within the framework of a dual-learning systems (DLS) model. This model predicts that successful speech category learning is initially mediated by an explicit, reflective learning system that frequently utilizes unidimensional rules, with an eventual switch to a more implicit, reflexive learning system that utilizes multidimensional rules. Participants were explicitly instructed to focus and/or ignore the pitch height dimension, the pitch direction dimension, or were given no explicit prime. Our results show that instruction instructing participants to focus on pitch direction, and instruction diverting attention away from pitch height, resulted in enhanced tone categorization. Computational modeling of participant responses suggested that instruction related to pitch direction led to faster and more frequent use of multidimensional reflexive strategies and enhanced perceptual selectivity along the previously underweighted pitch direction dimension.

  13. The Serotonin 2C Receptor Agonist Lorcaserin Attenuates Intracranial Self-Stimulation and Blocks the Reward-Enhancing Effects of Nicotine.

    PubMed

    Zeeb, Fiona D; Higgins, Guy A; Fletcher, Paul J

    2015-07-15

    Lorcaserin, a serotonin (5-hydroxytryptamine, 5-HT) 2C receptor agonist, was recently approved for the treatment of obesity. We previously suggested that 5-HT2C receptor agonists affect reward processes and reduce the rewarding effects of drugs of abuse. Here, we determined whether lorcaserin (1) decreases responding for brain stimulation reward (BSR) and (2) prevents nicotine from enhancing the efficacy of BSR. Rats were trained on the intracranial self-stimulation (ICSS) paradigm to nosepoke for BSR of either the dorsal raphé nucleus or left medial forebrain bundle. In Experiment 1, lorcaserin (0.3-1.0 mg/kg) dose-dependently reduced the efficacy of BSR. This effect was blocked by prior administration of the 5-HT2C receptor antagonist SB242084. In Experiment 2, separate groups of rats received saline or nicotine (0.4 mg/kg) for eight sessions prior to testing. Although thresholds were unaltered in saline-treated rats, nicotine reduced reward thresholds. An injection of lorcaserin (0.3 mg/kg) prior to nicotine prevented the reward-enhancing effect of nicotine across multiple test sessions. These results demonstrated that lorcaserin reduces the rewarding value of BSR and also prevents nicotine from facilitating ICSS. Hence, lorcaserin may be effective in treating psychiatric disorders, including obesity and nicotine addiction, by reducing the value of food or drug rewards.

  14. Superpulsed (Ga-As, 904 nm) low-level laser therapy (LLLT) attenuates inflammatory response and enhances healing of burn wounds.

    PubMed

    Gupta, Asheesh; Keshri, Gaurav K; Yadav, Anju; Gola, Shefali; Chauhan, Satish; Salhan, Ashok K; Bala Singh, Shashi

    2015-06-01

    Low-level laser therapy (LLLT) using superpulsed near-infrared light can penetrate deeper in the injured tissue and could allow non-pharmacological treatment for chronic wound healing. This study investigated the effects of superpulsed laser (Ga-As 904 nm, 200 ns pulse width; 100 Hz; 0.7 mW mean output power; 0.4 mW/cm(2) average irradiance; 0.2 J/cm(2) total fluence) on the healing of burn wounds in rats, and further explored the probable associated mechanisms of action. Irradiated group exhibited enhanced DNA, total protein, hydroxyproline and hexosamine contents compared to the control and silver sulfadiazine (reference care) treated groups. LLLT exhibited decreased TNF-α level and NF-kB, and up-regulated protein levels of VEGF, FGFR-1, HSP-60, HSP-90, HIF-1α and matrix metalloproteinases-2 and 9 compared to the controls. In conclusion, LLLT using superpulsed 904 nm laser reduced the inflammatory response and was able to enhance cellular proliferation, collagen deposition and wound contraction in the repair process of burn wounds. Photomicrographs showing no, absence inflammation and faster wound contraction in LLLT superpulsed (904 nm) laser treated burn wounds as compared to the non-irradiated control and silver sulfadiazine (SSD) ointment (reference care) treated wounds. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. What Children Infer from Social Categories

    ERIC Educational Resources Information Center

    Diesendruck, Gil; Eldror, Ehud

    2011-01-01

    Children hold the belief that social categories have essences. We investigated what kinds of properties children feel licensed to infer about a person based on social category membership. Seventy-two 4-6-year-olds were introduced to novel social categories defined as having one internal--psychological or biological--and one external--behavioral or…

  16. Incremental Bayesian Category Learning from Natural Language

    ERIC Educational Resources Information Center

    Frermann, Lea; Lapata, Mirella

    2016-01-01

    Models of category learning have been extensively studied in cognitive science and primarily tested on perceptual abstractions or artificial stimuli. In this paper, we focus on categories acquired from natural language stimuli, that is, words (e.g., "chair" is a member of the furniture category). We present a Bayesian model that, unlike…

  17. The Micro-Category Account of Analogy

    ERIC Educational Resources Information Center

    Green, Adam E.; Fugelsang, Jonathan A.; Kraemer, David J. M.; Dunbar, Kevin N.

    2008-01-01

    Here, we investigate how activation of mental representations of categories during analogical reasoning influences subsequent cognitive processing. Specifically, we present and test the central predictions of the "Micro-Category" account of analogy. This account emphasizes the role of categories in aligning terms for analogical mapping. In a…

  18. Incremental Bayesian Category Learning from Natural Language

    ERIC Educational Resources Information Center

    Frermann, Lea; Lapata, Mirella

    2016-01-01

    Models of category learning have been extensively studied in cognitive science and primarily tested on perceptual abstractions or artificial stimuli. In this paper, we focus on categories acquired from natural language stimuli, that is, words (e.g., "chair" is a member of the furniture category). We present a Bayesian model that, unlike…

  19. What Children Infer from Social Categories

    ERIC Educational Resources Information Center

    Diesendruck, Gil; Eldror, Ehud

    2011-01-01

    Children hold the belief that social categories have essences. We investigated what kinds of properties children feel licensed to infer about a person based on social category membership. Seventy-two 4-6-year-olds were introduced to novel social categories defined as having one internal--psychological or biological--and one external--behavioral or…

  20. Variable laser attenuator

    DOEpatents

    Foltyn, Stephen R.

    1988-01-01

    The disclosure relates to low loss, high power variable attenuators comprng one or more transmissive and/or reflective multilayer dielectric filters. The attenuator is particularly suitable to use with unpolarized lasers such as excimer lasers. Beam attenuation is a function of beam polarization and the angle of incidence between the beam and the filter and is controlled by adjusting the angle of incidence the beam makes to the filter or filters. Filters are selected in accordance with beam wavelength.

  1. Variable laser attenuator

    DOEpatents

    Foltyn, S.R.

    1987-05-29

    The disclosure relates to low loss, high power variable attenuators comprising one or more transmissive and/or reflective multilayer dielectric filters. The attenuator is particularly suitable to use with unpolarized lasers such as excimer lasers. Beam attenuation is a function of beam polarization and the angle of incidence between the beam and the filter and is controlled by adjusting the angle of incidence the beam makes to the filter or filters. Filters are selected in accordance with beam wavelength. 9 figs.

  2. Posterror slowing predicts rule-based but not information-integration category learning.

    PubMed

    Tam, Helen; Maddox, W Todd; Huang-Pollock, Cynthia L

    2013-12-01

    We examined whether error monitoring, operationalized as the degree to which individuals slow down after committing an error (i.e., posterror slowing), is differentially important in the learning of rule-based versus information-integration category structures. Rule-based categories are most efficiently solved through the application of an explicit verbal strategy (e.g., "sort by color"). In contrast, information-integration categories are believed to be learned in a trial-by-trial, associative manner. Our results indicated that posterror slowing predicts enhanced rule-based but not information-integration category learning. Implications for multiple category-learning systems are discussed.

  3. Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells.

    PubMed

    Shi, Yijie; Su, Chang; Cui, Wenyu; Li, Hongdan; Liu, Liwei; Feng, Bo; Liu, Ming; Su, Rongjian; Zhao, Liang

    2014-10-30

    Active targeting endocytosis mediated by the specific interaction between folic acid and its receptor has been a hotspot in biological therapy of many human cancers. Various studies have demonstrated that folate and its conjugates could facilitate the chemotherapeutic drug delivery into folate receptor (FR)-positive tumor cells in vitro and in vivo. In order to utilize FA-FR binding specificity to achieve targeted delivery of drugs into tumor cells, we prepared Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-β-cyclodextrin nanoparticles for enhancing drug delivery in cancer cells. On this context, the aim of our study was to develop a novel nano-delivery system for promoting tumor-targeting drug delivery in folate receptor-positive Hela cells. We prepared folic acid (FA)-decorated bovine serum albumin (BSA) conjugated carboxymethyl-β-cyclodextrin (CM-β-CD) nanoparticles (FA-BSA-CM-β-CD NPs) capable of entrapping a hydrophobic Gefitinib. It was observed that nanoparticles are monodisperse and spherical nanospheres with an average diameter of 90.2 nm and negative surface charge of -18.6 mV. FA-BSA-CM-β-CD NPs could greatly facilitate Gefitinib uptake and enhance the toxicity to folate receptor-positive Hela cells. Under the reaction between FA and FR, Gefitinib loaded FA-BSA-CM-β-CD NPs induced apoptosis of Hela cells through elevating the expression of caspase-3 and inhibited autophagy through decreasing the expressing of LC3. It also confirmed that clathrin-mediated endocytosis and macropinocytosis exerted great influence on the internalization of both NPs. These results demonstrated that FA may be an effective targeting molecule and FA-BSA-CM-β-CD NPs provided a new strategy for the treatment of human cancer cells which over-expressed folate receptors.

  4. Foxp3(+)-Treg cells enhanced by repeated low-dose gamma-irradiation attenuate ovalbumin-induced allergic asthma in mice.

    PubMed

    Park, Bum Soo; Hong, Gwan Ui; Ro, Jai Youl

    2013-05-01

    Gamma radiation is used for several therapeutic indications such as cancers and autoimmune diseases. Low-dose whole-body γ irradiation has been shown to activate immune responses in several ways, however, the effect and mechanism of irradiation on allergic asthma remains poorly understood. This study investigated whether or not irradiation exacerbates allergic asthma responses and its potential mechanism. C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) to induce asthma. The mice received whole-body irradiation once daily for 3 consecutive days with a dose of 0.667 Gy using (137)Cs γ rays 24 h before every OVA challenge. Repeated low-dose irradiation reduced OVA-specific IgE levels, the number of inflammatory cells including mast cells, goblet cell hyperplasia, collagen deposition, airway hyperresponsiveness, expression of inflammatory cytokines, CCL2/CCR2, as well as nuclear factor kappa B (NF-κB) and activator protein-1 activities. All of these factors were increased in BAL cells and lung tissue of OVA-challenged mice. Irradiation increased the number of Treg cells, expression of interleukin (IL)-10, IL-2 and IL-35 in BAL cells and lung tissue. Irradiation also increased Treg cell-expressed Foxp3 and IL-10 by NF-κB and RUNX1 in OVA-challenged mice. Furthermore, while Treg cell-expressing OX40 and IL-10 were enhanced in lung tissue or act-bone marrow-derived mast cells (BMMCs) with Treg cells, but BMMCs-expressing OX40L and TGF-β were decreased. The data suggest that irradiation enhances Foxp3(+)- and IL-10-producing Treg cells, which reduce OVA-induced allergic airway inflammation and tissue remodeling through the down-regulation of migration by the CCL2/CCR2 axis and activation of mast cells via OX40/OX40L in lung tissue of OVA-challenged mice.

  5. Development of essentialist thinking about religion categories in Northern Ireland (and the United States).

    PubMed

    Smyth, Kirsty; Feeney, Aidan; Eidson, R Cole; Coley, John D

    2017-03-01

    Social essentialism, the belief that members of certain social categories share unobservable properties, licenses expectations that those categories are natural and a good basis for inference. A challenge for cognitive developmental theory is to give an account of how children come to develop essentialist beliefs about socially important categories. Previous evidence from Israel suggests that kindergarteners selectively engage in essentialist reasoning about culturally salient (ethnicity) categories, and that this is attenuated among children in integrated schools. In 5 studies (N = 718) we used forced-choice (Study 1) and unconstrained (Studies 2-4) category-based inference tasks, and a questionnaire (Study 5) to study the development of essentialist reasoning about religion categories in Northern Ireland (Studies 1-3 & 5) and the U.S. (Study 4). Results show that, as in Israel, Northern Irish children selectively engage in essentialist reasoning about culturally salient (religion) categories, and that such reasoning is attenuated among children in integrated schools. However, the development trajectory of essentialist thinking and the patterns of attenuation among children attending integrated schools in Northern Ireland differ from the Israeli case. Meta-analysis confirmed this claim and ruled out an alternative explanation of the results based on community diversity. Although the Northern Irish and Israeli case studies illustrate that children develop selective essentialist beliefs about socially important categories, and that these beliefs are impacted by educational context, the differences between them emphasize the importance of historical, cultural, and political context in understanding conceptual development, and suggest that there may be more than one developmental route to social essentialism. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  6. Microwave variable waveguide attenuator.

    PubMed

    Fabeni, P; Mugnai, D; Pazzi, G P; Ranfagni, A

    2008-06-01

    A new type of cutoff attenuator is presented. The attenuator works in the X-band in conditions of almost perfect matching. This means that the phase of the wave, which propagates inside the guide, does not suffer sensible variation in the passage between X- and K(u)-bands. Moreover, the attenuator works directly in the X-band, avoiding the passage between waveguide and cable, thus eliminating spurious effects due to this (double) passage. Experimental results of attenuation and dephasing using a prototype are also presented.

  7. Color categories and color appearance

    PubMed Central

    Webster, Michael A.; Kay, Paul

    2011-01-01

    We examined categorical effects in color appearance in two tasks, which in part differed in the extent to which color naming was explicitly required for the response. In one, we measured the effects of color differences on perceptual grouping for hues that spanned the blue–green boundary, to test whether chromatic differences across the boundary were perceptually exaggerated. This task did not require overt judgments of the perceived colors, and the tendency to group showed only a weak and inconsistent categorical bias. In a second case, we analyzed results from two prior studies of hue scaling of chromatic stimuli (De Valois, De Valois, Switkes, & Mahon, 1997; Malkoc, Kay, & Webster, 2005), to test whether color appearance changed more rapidly around the blue–green boundary. In this task observers directly judge the perceived color of the stimuli and these judgments tended to show much stronger categorical effects. The differences between these tasks could arise either because different signals mediate color grouping and color appearance, or because linguistic categories might differentially intrude on the response to color and/or on the perception of color. Our results suggest that the interaction between language and color processing may be highly dependent on the specific task and cognitive demands and strategies of the observer, and also highlight pronounced individual differences in the tendency to exhibit categorical responses. PMID:22176751

  8. A history of chorological categories.

    PubMed

    Fattorini, S

    2016-09-01

    One of the purposes of the research program referred to as "systematic biogeography" is the use of species distributions to identify regions and reconstruct biotic area relationships. The reverse, i.e. to group species according to the areas that they live in, leads to the recognition of chorological categories. Biogeographers, working under these two different approaches, have proposed several terms to refer to groups of species that have similar distributions, such as "element", "chorotype" and "component". A historical reconstruction, including semantic observations and philosophical implications, shows that these terms have been used in a variety of senses. The word "component" should not be used in biogeography. The word "element" has been used to identify both a group of species defined according to the biogeographic areas they occupy and a group of species with an assumed shared biogeographic history. It is especially because of the influence of the dispersalist paradigm, which dominated evolutionary thought until the mid-twentieth century, that the second definition has been frequently adopted. The term "element" is therefore ambiguous and its use should always be associated with an explicit definition. The word "chorotype" should be used to define groups of species with similar ranges when no causal assumption is made. The concept of "chorotype," finally, should not be confounded with other concepts such as distributional pattern, cenocron, horofauna, biota, endemic area, area of endemism, biotic element, and generalized track, which are also discussed in this paper.

  9. Enhancement of Th1-biased protective immunity against avian influenza H9N2 virus via oral co-administration of attenuated Salmonella enterica serovar Typhimurium expressing chicken interferon-α and interleukin-18 along with an inactivated vaccine

    PubMed Central

    2012-01-01

    Background Control of currently circulating re-assorted low-pathogenicity avian influenza (LPAI) H9N2 is a major concern for both animal and human health. Thus, an improved LPAI H9N2 vaccination strategy is needed to induce complete immunity in chickens against LPAI H9N2 virus strains. Cytokines play a crucial role in mounting both the type and extent of an immune response generated following infection with a pathogen or after vaccination. To improve the efficacy of inactivated LPAI H9N2 vaccine, attenuated Salmonella enterica serovar Typhimurium was used for oral co-administration of chicken interferon-α (chIFN-α) and chicken interleukin-18 (chIL-18) as natural immunomodulators. Results Oral co-administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18, prior to vaccination with inactivated AI H9N2 vaccine, modulated the immune response of chickens against the vaccine antigen through enhanced humoral and Th1-biased cell-mediated immunity, compared to chickens that received single administration of S. enterica serovar Typhimurium expressing either chIFN-α or chIL-18. To further test the protective efficacy of this improved vaccination regimen, immunized chickens were intra-tracheally challenged with a high dose of LPAI H9N2 virus. Combined administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18 showed markedly enhanced protection compared to single administration of the construct, as determined by mortality, clinical severity, and feed and water intake. This enhancement of protective immunity was further confirmed by reduced rectal shedding and replication of AIV H9N2 in different tissues of challenged chickens. Conclusions Our results indicate the value of combined administration of chIFN-α and chIL-18 using a Salmonella vaccine strain to generate an effective immunization strategy in chickens against LPAI H9N2. PMID:22776696

  10. Categories of quantum and classical channels

    NASA Astrophysics Data System (ADS)

    Coecke, Bob; Heunen, Chris; Kissinger, Aleks

    2016-12-01

    We introduce a construction that turns a category of pure state spaces and operators into a category of observable algebras and superoperators. For example, it turns the category of finite-dimensional Hilbert spaces into the category of finite-dimensional C*-algebras and completely positive maps. In particular, the new category contains both quantum and classical channels, providing elegant abstract notions of preparation and measurement. We also consider nonstandard models that can be used to investigate which notions from algebraic quantum information theory are operationally justifiable.

  11. Baicalin inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances Pseudomonas aeruginosa clearance in a mouse peritoneal implant infection model.

    PubMed

    Luo, Jing; Dong, Biying; Wang, Ke; Cai, Shuangqi; Liu, Tangjuan; Cheng, Xiaojing; Lei, Danqing; Chen, Yanling; Li, Yanan; Kong, Jinliang; Chen, Yiqiang

    2017-01-01

    The quorum sensing (QS) circuit plays a role in the precise regulation of genes controlling virulence factors and biofilm formation in Pseudomonas aeruginosa. QS-controlled biofilm formation by Pseudomonas aeruginosa in clinical settings has remained controversial due to emerging drug resistance; therefore, screening diverse compounds for anti-biofilm or anti-QS activities is important. This study demonstrates the ability of sub-minimum inhibitory concentrations (sub-MICs) of baicalin, an active natural compound extracted from the traditional Chinese medicinal Scutellaria baicalensis, to inhibit the formation of Pseudomonas aeruginosa biofilms and enhance the bactericidal effects of various conventional antibiotics in vitro. In addition, baicalin exerted dose-dependent inhibitory effects on virulence phenotypes (LasA protease, LasB elastase, pyocyanin, rhamnolipid, motilities and exotoxin A) regulated by QS in Pseudomonas aeruginosa. Moreover, the expression levels of QS-regulatory genes, including lasI, lasR, rhlI, rhlR, pqsR and pqsA, were repressed after sub-MIC baicalin treatment, resulting in significant decreases in the QS signaling molecules 3-oxo-C12-HSL and C4-HSL, confirming the ability of baicalin-mediated QS inhibition to alter gene and protein expression. In vivo experiments indicated that baicalin treatment reduces Pseudomonas aeruginosa pathogenicity in Caenorhabditis elegans. Greater worm survival in the baicalin-treated group manifested as an increase in the LT50 from 24 to 96 h. In a mouse peritoneal implant infection model, baicalin treatment enhanced the clearance of Pseudomonas aeruginosa from the implants of mice infected with Pseudomonas aeruginosa compared with the control group. Moreover, the combination of baicalin and antibiotics significantly reduced the numbers of colony-forming units in the implants to a significantly greater degree than antibiotic treatment alone. Pathological and histological analyses revealed mitigation of the

  12. Baicalin inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances Pseudomonas aeruginosa clearance in a mouse peritoneal implant infection model

    PubMed Central

    Wang, Ke; Cai, Shuangqi; Liu, Tangjuan; Cheng, Xiaojing; Lei, Danqing; Chen, Yanling; Li, Yanan; Kong, Jinliang; Chen, Yiqiang

    2017-01-01

    The quorum sensing (QS) circuit plays a role in the precise regulation of genes controlling virulence factors and biofilm formation in Pseudomonas aeruginosa. QS-controlled biofilm formation by Pseudomonas aeruginosa in clinical settings has remained controversial due to emerging drug resistance; therefore, screening diverse compounds for anti-biofilm or anti-QS activities is important. This study demonstrates the ability of sub-minimum inhibitory concentrations (sub-MICs) of baicalin, an active natural compound extracted from the traditional Chinese medicinal Scutellaria baicalensis, to inhibit the formation of Pseudomonas aeruginosa biofilms and enhance the bactericidal effects of various conventional antibiotics in vitro. In addition, baicalin exerted dose-dependent inhibitory effects on virulence phenotypes (LasA protease, LasB elastase, pyocyanin, rhamnolipid, motilities and exotoxin A) regulated by QS in Pseudomonas aeruginosa. Moreover, the expression levels of QS-regulatory genes, including lasI, lasR, rhlI, rhlR, pqsR and pqsA, were repressed after sub-MIC baicalin treatment, resulting in significant decreases in the QS signaling molecules 3-oxo-C12-HSL and C4-HSL, confirming the ability of baicalin-mediated QS inhibition to alter gene and protein expression. In vivo experiments indicated that baicalin treatment reduces Pseudomonas aeruginosa pathogenicity in Caenorhabditis elegans. Greater worm survival in the baicalin-treated group manifested as an increase in the LT50 from 24 to 96 h. In a mouse peritoneal implant infection model, baicalin treatment enhanced the clearance of Pseudomonas aeruginosa from the implants of mice infected with Pseudomonas aeruginosa compared with the control group. Moreover, the combination of baicalin and antibiotics significantly reduced the numbers of colony-forming units in the implants to a significantly greater degree than antibiotic treatment alone. Pathological and histological analyses revealed mitigation of the

  13. Fucose-containing fraction of Ling-Zhi enhances lipid rafts-dependent ubiquitination of TGFβ receptor degradation and attenuates breast cancer tumorigenesis

    PubMed Central

    Tsao, Shu-Ming; Hsu, Hsien-Yeh

    2016-01-01

    Ganoderma lucidum exerts antitumor activity, but the mechanism of G. lucidum polysaccharides on cancer is unclear. Here, we demonstrated that a fucose-containing fraction of Ling-Zhi (FFLZ) reduced tumor size and suppressed metastasis in vivo. Furthermore, FFLZ inhibited breast cancer cell migration and altered the epithelial-to-mesenchymal transition (EMT) phenotype. Transforming growth factor-β receptor (TGFR) pathways act as key mediators to promote tumor progression and metastasis. We found that FFLZ down-regulated TGFR and downstream signaling pathways, including the phosphorylation of Smad2/3 and the expression of Smad4. In an investigation of the underlying mechanisms, we found that FFLZ enhanced the Smurf2-dependent ubiquitination of TGFR by disrupting the balance of the lipid rafts, promoted the “re-localization” of the TGFR to the caveolae, and facilitated the degradation of TGFR. Together, our data indicated that FFLZ is associated with the inhibition of EMT and the prevention of metastasis by promoting ubiquitination-dependent TGFR degradation and abolishing TGFR signaling pathways. Moreover, the combination of FFLZ and trastuzumab synergistically inhibited the viability of certain trastuzumab-resistant human breast cancer cells. In summary, our current findings indicate that FFLZ is a potential therapeutic or dietary supplemental agent for cancer patients and that it functions via the caveolin-1/Smad7/Smurf2-dependent ubiquitin-mediated degradation of TGFR. PMID:27830743

  14. The novel micro-opioid receptor antagonist, [N-allyl-Dmt(1)]endomorphin-2, attenuates the enhancement of GABAergic neurotransmission by ethanol.

    PubMed

    Li, Qiang; Okada, Yoshio; Marczak, Ewa; Wilson, Wilkie A; Lazarus, Lawrence H; Swartzwelder, H S

    2009-01-01

    We investigated the effects of [N-allyl-Dmt(1)]endomorphin-2 (TL-319), a novel and highly potent micro-opioid receptor antagonist, on ethanol (EtOH)-induced enhancement of GABA(A) receptor-mediated synaptic activity in the hippocampus. Evoked and spontaneous inhibitory postsynaptic currents (eIPSCs and sIPSCs) were isolated from CA1 pyramidal cells from brain slices of male rats using whole-cell patch-clamp techniques. TL-319 had no effect on the baseline amplitude of eIPSCs or the frequency of sIPSCs. However, it induced a dose-dependent suppression of an ethanol-induced increase of sIPSC frequency with full reversal at concentrations of 500 nM and higher. The non-specific competitive opioid receptor antagonist naltrexone also suppressed EtOH-induced increases in sIPSC frequency but only at a concentration of 60 microM. These data indicate that blockade of micro-opioid receptors by low concentrations of [N-allyl-Dmt(1)]endomorphin-2 can reverse ethanol-induced increases in GABAergic neurotransmission and possibly alter its anxiolytic or sedative effects. This suggests the possibility that high potency opioid antagonists may emerge as possible candidate compounds for the treatment of ethanol addiction.

  15. The human milk oligosaccharide 2'-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine.

    PubMed

    Good, Misty; Sodhi, Chhinder P; Yamaguchi, Yukihiro; Jia, Hongpeng; Lu, Peng; Fulton, William B; Martin, Laura Y; Prindle, Thomas; Nino, Diego F; Zhou, Qinjie; Ma, Congrong; Ozolek, John A; Buck, Rachael H; Goehring, Karen C; Hackam, David J

    2016-10-01

    Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2'-fucosyllactose (2'FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2'FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2'FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2'FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2'FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2'FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2'FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC.

  16. Hydrogen gas attenuates sevoflurane neurotoxicity through inhibiting nuclear factor κ-light-chain-enhancer of activated B cells signaling and proinflammatory cytokine release in neonatal rats.

    PubMed

    Shi, Yiwei; Wang, Gang; Li, Jinyuan; Yu, Wenli

    2017-09-18

    Anesthesia neurotoxicity in developing brain has gained increasing attention. However, knowledge regarding its mitigating strategies remains scant. Sevoflurane, a commonly used anesthetic, is responsible for learning and memory deficits in neonates. Molecular hydrogen is reported to be a potential neuroprotective agent because of its antioxidative and anti-inflammatory activities. This study aimed to investigate the effect of hydrogen gas on sevoflurane neurotoxicity. The newborn rats were treated with sevoflurane and/or hydrogen gas for 2 h. Spatial recognition memory and fear memory were determined by Y-maze and fear conditioning tests at 10 weeks of age. Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and proinflammatory cytokine levels were detected using western blot analysis. The data showed that the spatial recognition memory and fear memory of the rats treated with sevoflurane decreased compared with the control, and the cognitive function of the rats treated with sevoflurane and hydrogen gas significantly increased in comparison with treatment with sevoflurane alone. Moreover, hydrogen gas suppressed NF-κB phosphorylation and nuclear translocation and reduced the production of interleukin-1β, interleukin-6, and tumor necrosis factor-α following sevoflurane administration. Thus, the results proposed that hydrogen gas might protect against sevoflurane neurotoxicity by inhibiting NF-κB activation and proinflammatory cytokine release, providing a novel therapeutic strategy for anesthesia neurotoxicity.

  17. Optimal sequencing during category learning: Testing a dual-learning systems perspective.

    PubMed

    Noh, Sharon M; Yan, Veronica X; Bjork, Robert A; Maddox, W Todd

    2016-10-01

    Recent studies demonstrate that interleaving the exemplars of different categories, rather than blocking exemplars by category, can enhance inductive learning-the ability to categorize new exemplars-presumably because interleaving affords discriminative contrasts between exemplars from different categories. Consistent with this view, other studies have demonstrated that decreasing between-category similarity and increasing within-category variability can eliminate or even reverse the interleaving benefit. We tested another hypothesis, one based on the dual-learning systems framework-namely, that the optimal schedule for learning categories should depend on an interaction of the cognitive system that mediates learning and the structure of the particular category being learned. Blocking should enhance rule-based category learning, which is mediated by explicit, hypothesis-testing processes, whereas interleaving should enhance information-integration category learning, which is mediated by an implicit, procedural-based learning system. Consistent with this view, we found a crossover interaction between schedule (blocked vs. interleaved) and category structure (rule-based vs. information-integration). Copyright © 2016 Elsevier B.V. All rights reserved.

  18. The human milk oligosaccharide 2′-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine

    PubMed Central

    Good, Misty; Sodhi, Chhinder P.; Yamaguchi, Yukihiro; Jia, Hongpeng; Lu, Peng; Fulton, William B.; Martin, Laura Y.; Prindle, Thomas; Nino, Diego F.; Zhou, Qinjie; Ma, Congrong; Ozolek, John A.; Buck, Rachael H.; Goehring, Karen C.; Hackam, David J.

    2016-01-01

    Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2′-fucosyllactose (2′FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2′FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2′FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2′FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2′FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2′FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2′FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC. PMID:27609061

  19. Activation of SIRT1 Attenuates Klotho Deficiency-Induced Arterial Stiffness and Hypertension by Enhancing AMP-Activated Protein Kinase Activity.

    PubMed

    Gao, Diansa; Zuo, Zhong; Tian, Jing; Ali, Quaisar; Lin, Yi; Lei, Han; Sun, Zhongjie

    2016-11-01

    Arterial stiffness is an independent risk factor for stroke and myocardial infarction. This study was designed to investigate the role of SIRT1, an important deacetylase, and its relationship with Klotho, a kidney-derived aging-suppressor protein, in the pathogenesis of arterial stiffness and hypertension. We found that the serum level of Klotho was decreased by ≈45% in patients with arterial stiffness and hypertension. Interestingly, Klotho haplodeficiency caused arterial stiffening and hypertension, as evidenced by significant increases in pulse wave velocity and blood pressure in Klotho-haplodeficient (KL(+/-)) mice. Notably, the expression and activity of SIRT1 were decreased significantly in aortic endothelial and smooth muscle cells in KL(+/-) mice, suggesting that Klotho deficiency downregulates SIRT1. Treatment with SRT1720 (15 mg/kg/d, IP), a specific SIRT1 activator, abolished Klotho deficiency-induced arterial stiffness and hypertension in KL(+/-) mice. Klotho deficiency was associated with significant decreases in activities of AMP-activated protein kinase α (AMPKα) and endothelial NO synthase (eNOS) in aortas, which were abolished by SRT1720. Furthermore, Klotho deficiency upregulated NADPH oxidase activity and superoxide production, increased collagen expression, and enhanced elastin fragmentation in the media of aortas. These Klotho deficiency-associated changes were blocked by SRT1720. In conclusion, this study provides the first evidence that Klotho deficiency downregulates SIRT1 activity in arterial endothelial and smooth muscle cells. Pharmacological activation of SIRT1 may be an effective therapeutic strategy for arterial stiffness and hypertension. © 2016 American Heart Association, Inc.

  20. Melatonin attenuated adipogenesis through reduction of the CCAAT/enhancer binding protein beta by regulating the glycogen synthase 3 beta in human mesenchymal stem cells.

    PubMed

    Rhee, Yun-Hee; Ahn, Jin-Chul

    2016-06-01

    Adipogenic differentiation is characterized by an increase in two major transcription factors: peroxisome proliferator-activated receptor gamma (PPARγ) and the CCAAT/enhancer binding protein alpha (C/EBPα). These two signals are influenced by C/EBPβ and C/EBPδ and cross-regulate each other's expression during the initial stages of adipogenesis. Melatonin has been known to act as not only a direct scavenger of free radicals but also an inhibitor of glycogen synthase kinase 3β (GSK-3β). Here, we report that melatonin inhibits the adipogenic differentiation of human mesenchymal stem cells (hMSCs) which is due to the regulations of C/EBPβ in the early stage of adipogenic differentiation. Melatonin reduced the lipid accumulation, adiponectin, and lipoprotein lipase (LPL) during the adipogenic differentiation of hMSCs. Since C/EBPβ has been associated with the activation of PPARγ and the consensus site of ERK/GSK-3β, PPARγ and β-catenin were detected by immunofluorescence staining after pretreatment of melatonin. Melatonin blocked the activation of PPARγ which induced the degradation of β-catenin. Melatonin also decreased the levels of cyclic adenosine-3,5-monophosphate (cAMP) and reactive oxygen species (ROS). The cAMP triggered the activity of C/EBPβ which is a critical inducer of PPARγ and C/EBPα activation in the early stage of adipogenic differentiation, and this is further affected by ROS production. The adipogenic marker proteins such as PPARγ, C/EBPα, C/EBPβ, and pERK were also decreased by melatonin. In summary, melatonin inhibited the cAMP synthesis through ROS reduction and the phosphorylation of the ERK/GSK-3β site which is known to be responsible for C/EBPβ activation for adipogenic differentiation in hMSCs.

  1. Engineering an improved cell cycle-regulatable herpes simplex virus type 1 amplicon vector with enhanced transgene expression in proliferating cells yet attenuated activities in resting cells.

    PubMed

    Wang, Grace Y; Ho, Ivy A W; Sia, Kian C; Miao, L; Hui, Kam M; Lam, Paula Y P

    2007-03-01

    We previously generated a herpes simplex virus type 1 (HSV-1)-based amplicon vector (denoted pC8-36) in which gene expression from the minimal cyclin A promoter is repressed by preventing the binding of a trans-activating protein, Gal4-NF-YA, to it through selective interaction with the transcriptional repressor protein CDF-1. Because CDF-1 is absent in actively dividing cells, transgene expression conferred by the pC8-36 vector is therefore cell cycle dependent. As gene therapy evolves to become a promising therapeutic modality for many human diseases, there is an increasing need to further improve the kinetics of gene regulation. In the present study, we examined whether the availability of more binding sites for CDF-1 repressor proteins could enhance transgene expression. Using an overlap extension polymerase chain reaction (PCR) method, the CDE and CHR elements within the minimum cyclin A promoter were multimerized to contain two, three, and six copies of the designated CDE/CHR sequence. Interestingly, our results demonstrated that six-copy CDE/CHR sequence motifs (pC8-6CC-Luc) conferred an approximately 20-fold increase in the ratio of cell cycle regulation compared with the previous reported construct. Further, the overall transcriptional activities mediated by pC8-6CC-Luc were stronger compared with the native human survivin promoter, which consists of three copies of the CDE element and one copy of the CHR element. pC8-6CC-Luc contained, in essence, only the synthetic six-copy CDE/CHR sequence motif (about 262 bp). In comparison with other native endogenous promoters, which usually contain many other transcription binding sites, pC8-6CC-Luc amplicon vectors should confer better regulated and consistent transgene expression and may be considered a gene delivery vector of choice to target actively proliferating tumor cells.

  2. How language shapes the cultural inheritance of categories

    PubMed Central

    Gelman, Susan A.; Roberts, Steven O.

    2017-01-01

    It is widely recognized that language plays a key role in the transmission of human culture, but relatively little is known about the mechanisms by which language simultaneously encourages both cultural stability and cultural innovation. This paper examines this issue by focusing on the use of language to transmit categories, focusing on two universal devices: labels (e.g., shark, woman) and generics (e.g., “sharks attack swimmers”; “women are nurturing”). We propose that labels and generics each assume two key principles: norms and essentialism. The normative assumption permits transmission of category information with great fidelity, whereas essentialism invites innovation by means of an open-ended, placeholder structure. Additionally, we sketch out how labels and generics aid in conceptual alignment and the progressive “looping” between categories and cultural practices. In this way, human language is a technology that enhances and expands the categorization capacities that we share with other animals. PMID:28739931

  3. 75 FR 62694 - Implementation Guidance for Physical Protection of Byproduct Material Category 1 and Category 2...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-13

    ... and Category 2 Quantities of Radioactive Material; Draft Guidance Document for Comment; Extension of... Category 2 quantities of radioactive material. The public comment period for this guidance was to have... use of Category 1 and Category 2 quantities of radioactive material into a new Part 37 of Title 10 of...

  4. Feature-Based versus Category-Based Induction with Uncertain Categories

    ERIC Educational Resources Information Center

    Griffiths, Oren; Hayes, Brett K.; Newell, Ben R.

    2012-01-01

    Previous research has suggested that when feature inferences have to be made about an instance whose category membership is uncertain, feature-based inductive reasoning is used to the exclusion of category-based induction. These results contrast with the observation that people can and do use category-based induction when category membership is…

  5. Conceptual influences on category-based induction

    PubMed Central

    Gelman, Susan A.; Davidson, Natalie S.

    2013-01-01

    One important function of categories is to permit rich inductive inferences. Prior work shows that children use category labels to guide their inductive inferences. However, there are competing theories to explain this phenomenon, differing in the roles attributed to conceptual information versus perceptual similarity. Seven experiments with 4- to 5-year-old children and adults (N = 344) test these theories by teaching categories for which category membership and perceptual similarity are in conflict, and varying the conceptual basis of the novel categories. Results indicate that for non-natural kind categories that have little conceptual coherence, children make inferences based on perceptual similarity, whereas adults make inferences based on category membership. In contrast, for basic- and ontological-level categories that have a principled conceptual basis, children and adults alike make use of category membership more than perceptual similarity as the basis of their inferences. These findings provide evidence in favor of the role of conceptual information in preschoolers’ inferences, and further demonstrate that labeled categories are not all equivalent; they differ in their inductive potential. PMID:23517863

  6. Incremental Bayesian Category Learning From Natural Language.

    PubMed

    Frermann, Lea; Lapata, Mirella

    2016-08-01

    Models of category learning have been extensively studied in cognitive science and primarily tested on perceptual abstractions or artificial stimuli. In this paper, we focus on categories acquired from natural language stimuli, that is, words (e.g., chair is a member of the furniture category). We present a Bayesian model that, unlike previous work, learns both categories and their features in a single process. We model category induction as two interrelated subproblems: (a) the acquisition of features that discriminate among categories, and (b) the grouping of concepts into categories based on those features. Our model learns categories incrementally using particle filters, a sequential Monte Carlo method commonly used for approximate probabilistic inference that sequentially integrates newly observed data and can be viewed as a plausible mechanism for human learning. Experimental results show that our incremental learner obtains meaningful categories which yield a closer fit to behavioral data compared to related models while at the same time acquiring features which characterize the learned categories. (An earlier version of this work was published in Frermann and Lapata .). Copyright © 2015 Cognitive Science Society, Inc.

  7. Procedural-based category learning in patients with Parkinson's disease: impact of category number and category continuity

    PubMed Central

    Filoteo, J. Vincent; Maddox, W. Todd

    2014-01-01

    Previously we found that Parkinson's disease (PD) patients are impaired in procedural-based category learning when category membership is defined by a nonlinear relationship between stimulus dimensions, but these same patients are normal when the rule is defined by a linear relationship (Maddox and Filoteo, 2001; Filoteo et al., 2005a,b). We suggested that PD patients' impairment was due to a deficit in recruiting “striatal units” to represent complex nonlinear rules. In the present study, we further examined the nature of PD patients' procedural-based deficit in two experiments designed to examine the impact of (1) the number of categories, and (2) category discontinuity on learning. Results indicated that PD patients were impaired only under discontinuous category conditions but were normal when the number of categories was increased from two to four. The lack of impairment in the four-category condition suggests normal integrity of striatal medium spiny cells involved in procedural-based category learning. In contrast, and consistent with our previous observation of a nonlinear deficit, the finding that PD patients were impaired in the discontinuous condition suggests that these patients are impaired when they have to associate perceptually distinct exemplars with the same category. Theoretically, this deficit might be related to dysfunctional communication among medium spiny neurons within the striatum, particularly given that these are cholinergic neurons and a cholinergic deficiency could underlie some of PD patients' cognitive impairment. PMID:24600355

  8. Polyethylene glycol-coated graphene oxide attenuates antigen-specific IgE production and enhanced antigen-induced T-cell reactivity in ovalbumin-sensitized BALB/c mice

    PubMed Central

    Wu, Hsin-Ying; Lin, Kun-Ju; Wang, Ping-Yen; Lin, Chi-Wen; Yang, Hong-Wei; Ma, Chen-Chi M; Lu, Yu-Jen; Jan, Tong-Rong

    2014-01-01

    Background Graphene oxide (GO) is a promising nanomaterial for potential application in the versatile field of biomedicine. Graphene-based nanomaterials have been reported to modulate the functionality of immune cells in culture and to induce pulmonary inflammation in mice. Evidence pertaining to the interaction between graphene-based nanomaterials and the immune system in vivo remains scarce. The present study investigated the effect of polyethylene glycol-coated GO (PEG-GO) on antigen-specific immunity in vivo. Methods BALB/c mice were intravenously administered with a single dose of PEG-GO (0.5 or 1 mg/kg) 1 hour before ovalbumin (OVA) sensitization, and antigen-specific antibody production and splenocyte reactivity were measured 7 days later. Results Exposure to PEG-GO significantly attenuated the serum level of OVA-specific immunoglobulin E. The production of interferon-γ and interleukin-4 by splenocytes restimulated with OVA in culture was enhanced by treatment with PEG-GO. In addition, PEG-GO augmented the metabolic activity of splenocytes restimulated with OVA but not with the T-cell mitogen concanavalin A. Conclusion Collectively, these results demonstrate that systemic exposure to PEG-GO modulates several aspects of antigen-specific immune responses, including the serum production of immunoglobulin E and T-cell functionality. PMID:25228804

  9. Polyethylene glycol-coated graphene oxide attenuates antigen-specific IgE production and enhanced antigen-induced T-cell reactivity in ovalbumin-sensitized BALB/c mice.

    PubMed

    Wu, Hsin-Ying; Lin, Kun-Ju; Wang, Ping-Yen; Lin, Chi-Wen; Yang, Hong-Wei; Ma, Chen-Chi M; Lu, Yu-Jen; Jan, Tong-Rong

    2014-01-01

    Graphene oxide (GO) is a promising nanomaterial for potential application in the versatile field of biomedicine. Graphene-based nanomaterials have been reported to modulate the functionality of immune cells in culture and to induce pulmonary inflammation in mice. Evidence pertaining to the interaction between graphene-based nanomaterials and the immune system in vivo remains scarce. The present study investigated the effect of polyethylene glycol-coated GO (PEG-GO) on antigen-specific immunity in vivo. BALB/c mice were intravenously administered with a single dose of PEG-GO (0.5 or 1 mg/kg) 1 hour before ovalbumin (OVA) sensitization, and antigen-specific antibody production and splenocyte reactivity were measured 7 days later. Exposure to PEG-GO significantly attenuated the serum level of OVA-specific immunoglobulin E. The production of interferon-γ and interleukin-4 by splenocytes restimulated with OVA in culture was enhanced by treatment with PEG-GO. In addition, PEG-GO augmented the metabolic activity of splenocytes restimulated with OVA but not with the T-cell mitogen concanavalin A. Collectively, these results demonstrate that systemic exposure to PEG-GO modulates several aspects of antigen-specific immune responses, including the serum production of immunoglobulin E and T-cell functionality.

  10. Scene categorization with multiscale category-specific visual words

    NASA Astrophysics Data System (ADS)

    Qin, Jianzhao; Yung, Nelson H. C.

    2009-04-01

    We propose a novel scene categorization method based on multiscale category-specific visual words. The novelty of the proposed method lies in two aspects: (1) visual words are quantized in a multiscale manner that combines the global-feature-based and local-feature-based scene categorization approaches into a uniform framework; (2) unlike traditional visual word creation methods, which quantize visual words from the entire set of training, we form visual words from the training images grouped in different categories and then collate visual words from different categories to form the final codebook. This generation strategy is capable of enhancing the discriminative ability of the visual words, which is useful for achieving better classification performance. The proposed method is evaluated over two scene classification data sets with 8 and 13 scene categories, respectively. The experimental results show that the classification performance is significantly improved by using the multiscale category-specific visual words over that achieved by using the traditional visual words. Moreover, the proposed method is comparable with the best methods reported in previous literature in terms of classification accuracy rate (88.81% and 85.05% accuracy rates for data sets 1 and 2, respectively) and has the advantage in simplicity.

  11. Adaptation of the Endogenous Salmonella enterica Serovar Typhi clyA-Encoded Hemolysin for Antigen Export Enhances the Immunogenicity of Anthrax Protective Antigen Domain 4 Expressed by the Attenuated Live-Vector Vaccine Strain CVD 908-htrA

    PubMed Central

    Galen, James E.; Zhao, Licheng; Chinchilla, Magaly; Wang, Jin Yuan; Pasetti, Marcela F.; Green, Jeffrey; Levine, Myron M.

    2004-01-01

    Bacterial live-vector vaccines aim to deliver foreign antigens to the immune system and induce protective immune responses, and surface-expressed or secreted antigens are generally more immunogenic than cytoplasmic constructs. We hypothesize that an optimum expression system will use an endogenous export system to avoid the need for large amounts of heterologous DNA encoding additional proteins. Here we describe the cryptic chromosomally encoded 34-kDa cytolysin A hemolysin of Salmonella enterica serovar Typhi (ClyA) as a novel export system for the expression of heterologous antigens in the supernatant of attenuated Salmonella serovar Typhi live-vector vaccine strains. We constructed a genetic fusion of ClyA to the reporter green fluorescent protein and showed that in Salmonella serovar Typhi CVD 908-htrA, the fusion protein retains biological activity in both domains and is exported into the supernatant of an exponentially growing live vector in the absence of detectable bacterial lysis. The utility of ClyA for enhancing the immunogenicity of an otherwise problematic antigen was demonstrated by engineering ClyA fused to the domain 4 (D4) moiety of Bacillus anthracis protective antigen (PA). A total of 11 of 15 mice immunized intranasally with Salmonella serovar Typhi exporting the protein fusion manifested fourfold or greater rises in serum anti-PA immunoglobulin G, compared with only 1 of 16 mice immunized with the live vector expressing cytoplasmic D4 (P = 0.0002). In addition, the induction of PA-specific gamma interferon and interleukin 5 responses was observed in splenocytes. This technology offers exceptional versatility for enhancing the immunogenicity of bacterial live-vector vaccines. PMID:15557633

  12. Attenuation of pCREB and Egr1 expression in the insular and anterior cingulate cortices associated with enhancement of CFA-evoked mechanical hypersensitivity after repeated forced swim stress.

    PubMed

    Imbe, Hiroki; Kimura, Akihisa

    2017-09-01

    The perception and response to pain are severely impacted by exposure to stressors. In some animal models, stress increases pain sensitivity, which is termed stress-induced hyperalgesia (SIH). The insular cortex (IC) and anterior cingulate cortex (ACC), which are typically activated by noxious stimuli, affect pain perception through the descending pain modulatory system. In the present study, we examined the expression of phospho-cAMP response element-binding protein (pCREB) and early growth response 1 (Egr1) in the IC and ACC at 3h (the acute phase of peripheral tissue inflammation) after complete Freund's adjuvant (CFA) injection in naïve rats and rats preconditioned with forced swim stress (FS) to clarify the effect of FS, a stressor, on cortical cell activities in the rats showing SIH induced by FS. The CFA injection into the hindpaw induced mechanical hypersensitivity and increased the expression of the pCREB and Egr1 in the IC and ACC at 3h after the injection. FS (day 1, 10min; days 2-3, 20min) prior to the CFA injection enhanced the CFA-induced mechanical hypersensitivity and attenuated the increase in the expression of pCREB and Egr1 in the IC and ACC. These findings suggested that FS modulates the CFA injection-induced neuroplasticity in the IC and ACC to enhance the mechanical hypersensitivity. These findings are thought to signify stressor-induced dysfunction of the descending pain modulatory system. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Brazilian Green Propolis Extract Synergizes with Protoporphyrin IX-mediated Photodynamic Therapy via Enhancement of Intracellular Accumulation of Protoporphyrin IX and Attenuation of NF-κB and COX-2.

    PubMed

    Wang, Cheng-Cheng; Wang, Yu-Xuan; Yu, Nian-Qin; Hu, Die; Wang, Xiao-Yan; Chen, Xing-Guang; Liao, You-Wei; Yao, Jing; Wang, Hao; He, Ling; Wu, Liang

    2017-05-04

    Brazilian green propolis (BGP) is noted for its impressive antitumor effects and has been used as a folk medicine in various cultures for many years. It has been demonstrated that BGP could enhance the cytotoxic effect of cytostatic drugs on tumor cells. Photodynamic therapy (PDT) is a therapeutic approach used against malignant cells. To assess the synergistic effect of BGP extract on protoporphyrin IX (PpIX)-mediated photocytotoxicity, MTT assays were performed using A431 and HeLa cells. TUNEL assay and Annexin V-FITC/PI staining were performed to confirm the induction of apoptosis. Western blotting analysis was performed to examine the pro-apoptotic proteins, anti-apoptotic proteins and inflammation related proteins in A431 cells. Intracellular accumulation of PpIX was examined by flow cytometry. The synergistic effect of BGP extract in PpIX-PDT was also evaluated with a xenograft model. Our findings reveal that BGP extract increased PpIX-mediated photocytotoxicity in A431 and HeLa cells. PpIX-PDT with BGP extract treatment resulted in a decrease in Bcl-xL and an increase in NOXA, Bax and caspase-3 cleavage. The protein expression levels of p-IKKα/β, NF-κB and COX-2 were upregulated by PpIX-PDT but significantly attenuated when in combination with BGP extract. BGP extract was also found to significantly enhance the intracellular accumulation of PpIX in A431 cells. BGP extract increased PpIX-mediated photocytotoxicity in a xenograft model as well. Our findings provide evidence for a synergistic effect of BGP extract in PpIX-PDT both in vitro and in vivo.

  14. On Flat Objects of Finitely Accessible Categories

    PubMed Central

    2013-01-01

    Flat objects of a finitely accessible additive category 𝒞 are described in terms of some objects of the associated functor category of 𝒞, called strongly flat functors. We study closure properties of the class of strongly flat functors, and we use them to deduce the known result that every object of a finitely accessible abelian category has a flat cover. PMID:24292562

  15. RADIO FREQUENCY ATTENUATOR

    DOEpatents

    Giordano, S.

    1963-11-12

    A high peak power level r-f attenuator that is readily and easily insertable along a coaxial cable having an inner conductor and an outer annular conductor without breaking the ends thereof is presented. Spaced first and second flares in the outer conductor face each other with a slidable cylindrical outer conductor portion therebetween. Dielectric means, such as water, contact the cable between the flares to attenuate the radio-frequency energy received thereby. The cylindrical outer conductor portion is slidable to adjust the voltage standing wave ratio to a low level, and one of the flares is slidable to adjust the attenuation level. An integral dielectric container is also provided. (AFC)

  16. Landing gear noise attenuation

    NASA Technical Reports Server (NTRS)

    Moe, Jeffrey W. (Inventor); Whitmire, Julia (Inventor); Kwan, Hwa-Wan (Inventor); Abeysinghe, Amal (Inventor)

    2011-01-01

    A landing gear noise attenuator mitigates noise generated by airframe deployable landing gear. The noise attenuator can have a first position when the landing gear is in its deployed or down position, and a second position when the landing gear is in its up or stowed position. The noise attenuator may be an inflatable fairing that does not compromise limited space constraints associated with landing gear retraction and stowage. A truck fairing mounted under a truck beam can have a compliant edge to allow for non-destructive impingement of a deflected fire during certain conditions.

  17. Behavioral demand modulates object category representation in the inferior temporal cortex

    PubMed Central

    Emadi, Nazli

    2014-01-01

    Visual object categorization is a critical task in our daily life. Many studies have explored category representation in the inferior temporal (IT) cortex at the level of single neurons and population. However, it is not clear how behavioral demands modulate this category representation. Here, we recorded from the IT single neurons in monkeys performing two different tasks with identical visual stimuli: passive fixation and body/object categorization. We found that category selectivity of the IT neurons was improved in the categorization compared with the passive task where reward was not contingent on image category. The category improvement was the result of larger rate enhancement for the preferred category and smaller response variability for both preferred and nonpreferred categories. These specific modulations in the responses of IT category neurons enhanced signal-to-noise ratio of the neural responses to discriminate better between the preferred and nonpreferred categories. Our results provide new insight into the adaptable category representation in the IT cortex, which depends on behavioral demands. PMID:25080572

  18. Social learning in animals: categories and mechanisms.

    PubMed

    Heyes, C M

    1994-05-01

    There has been relatively little research on the psychological mechanisms of social learning. This may be due, in part, to the practice of distinguishing categories of social learning in relation to ill-defined mechanisms (Davis, 1973; Galef, 1988). This practice both makes it difficult to identify empirically examples of different types of social learning, and gives the false impression that the mechanisms responsible for social learning are clearly understood. It has been proposed that social learning phenomena be subsumed within the categorization scheme currently used by investigators of asocial learning. This scheme distinguishes categories of learning according to observable conditions, namely, the type of experience that gives rise to a change in an animal (single stimulus vs. stimulus-stimulus relationship vs. response-reinforcer relationship), and the type of behaviour in which this change is detected (response evocation vs. learnability) (Rescorla, 1988). Specifically, three alignments have been proposed: (i) stimulus enhancement with single stimulus learning, (ii) observational conditioning with stimulus-stimulus learning, or Pavlovian conditioning, and (iii) observational learning with response-reinforcer learning, or instrumental conditioning. If, as the proposed alignments suggest, the conditions of social and asocial learning are the same, there is some reason to believe that the mechanisms underlying the two sets of phenomena are also the same. This is so if one makes the relatively uncontroversial assumption that phenomena which occur under similar conditions tend to be controlled by similar mechanisms. However, the proposed alignments are intended to be a set of hypotheses, rather than conclusions, about the mechanisms of social learning; as a basis for further research in which animal learning theory is applied to social learning. A concerted attempt to apply animal learning theory to social learning, to find out whether the same mechanisms are

  19. Attenuator And Conditioner

    SciTech Connect

    Anderson, Gene R.; Armendariz, Marcelino G.; Carson, Richard F.; Bryan, Robert P.; Duckett, III, Edwin B.; Kemme, Shanalyn Adair; McCormick, Frederick B.; Peterson, David W.

    2006-04-04

    An apparatus and method of attenuating and/or conditioning optical energy for an optical transmitter, receiver or transceiver module is disclosed. An apparatus for attenuating the optical output of an optoelectronic connector including: a mounting surface; an array of optoelectronic devices having at least a first end; an array of optical elements having at least a first end; the first end of the array of optical elements optically aligned with the first end of the array of optoelectronic devices; an optical path extending from the first end of the array of optoelectronic devices and ending at a second end of the array of optical elements; and an attenuator in the optical path for attenuating the optical energy emitted from the array of optoelectronic devices. Alternatively, a conditioner may be adapted in the optical path for conditioning the optical energy emitted from the array of optoelectronic devices.

  20. SEISMIC ATTENUATION FOR RESERVOIR CHARACTERIZATION

    SciTech Connect

    Joel Walls; M.T. Taner; Naum Derzhi; Gary Mavko; Jack Dvorkin

    2003-12-01

    We have developed and tested technology for a new type of direct hydrocarbon detection. The method uses inelastic rock properties to greatly enhance the sensitivity of surface seismic methods to the presence of oil and gas saturation. These methods include use of energy absorption, dispersion, and attenuation (Q) along with traditional seismic attributes like velocity, impedance, and AVO. Our approach is to combine three elements: (1) a synthesis of the latest rock physics understanding of how rock inelasticity is related to rock type, pore fluid types, and pore microstructure, (2) synthetic seismic modeling that will help identify the relative contributions of scattering and intrinsic inelasticity to apparent Q attributes, and (3) robust algorithms that extract relative wave attenuation attributes from seismic data. This project provides: (1) Additional petrophysical insight from acquired data; (2) Increased understanding of rock and fluid properties; (3) New techniques to measure reservoir properties that are not currently available; and (4) Provide tools to more accurately describe the reservoir and predict oil location and volumes. These methodologies will improve the industry's ability to predict and quantify oil and gas saturation distribution, and to apply this information through geologic models to enhance reservoir simulation. We have applied for two separate patents relating to work that was completed as part of this project.

  1. Fiber Optic Attenuators

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Mike Buzzetti designed a fiber optic attenuator while working at Jet Propulsion Laboratory, intended for use in NASA's Deep Space Network. Buzzetti subsequently patented and received an exclusive license to commercialize the device, and founded Nanometer Technologies to produce it. The attenuator functions without introducing measurable back-reflection or insertion loss, and is relatively insensitive to vibration and changes in temperature. Applications include cable television, telephone networks, other signal distribution networks, and laboratory instrumentation.

  2. Conventional Wisdom: Negotiating Conventions of Reference Enhances Category Learning

    ERIC Educational Resources Information Center

    Voiklis, John; Corter, James E.

    2012-01-01

    Collaborators generally coordinate their activities through communication, during which they readily negotiate a shared lexicon for activity-related objects. This social-pragmatic activity both recruits and affects cognitive and social-cognitive processes ranging from selective attention to perspective taking. We ask whether negotiating reference…

  3. SUSTAIN: A Network Model of Category Learning

    ERIC Educational Resources Information Center

    Love, Bradley C.; Medin, Douglas L.; Gureckis, Todd M.

    2004-01-01

    SUSTAIN (Supervised and Unsupervised STratified Adaptive Incremental Network) is a model of how humans learn categories from examples. SUSTAIN initially assumes a simple category structure. If simple solutions prove inadequate and SUSTAIN is confronted with a surprising event (e.g., it is told that a bat is a mammal instead of a bird), SUSTAIN…

  4. Category-Specificity in Visual Object Recognition

    ERIC Educational Resources Information Center

    Gerlach, Christian

    2009-01-01

    Are all categories of objects recognized in the same manner visually? Evidence from neuropsychology suggests they are not: some brain damaged patients are more impaired in recognizing natural objects than artefacts whereas others show the opposite impairment. Category-effects have also been demonstrated in neurologically intact subjects, but the…

  5. Category-Specificity in Visual Object Recognition

    ERIC Educational Resources Information Center

    Gerlach, Christian

    2009-01-01

    Are all categories of objects recognized in the same manner visually? Evidence from neuropsychology suggests they are not: some brain damaged patients are more impaired in recognizing natural objects than artefacts whereas others show the opposite impairment. Category-effects have also been demonstrated in neurologically intact subjects, but the…

  6. Category Coherence in Cross-Cultural Perspective.

    ERIC Educational Resources Information Center

    Malt, Barbara C.

    1995-01-01

    Major proposals that psychologists have made about how humans segment their world into categories are reviewed. The anthropological literature that bears on the same issues is explored, noting its implications for psychological theory. Cross-cultural data provide substantial constraints for theories of category coherence. (SLD)

  7. Faculty Role Categories: A Dean's Management Challenge

    ERIC Educational Resources Information Center

    Harvey, Michael G.; Sigerstad, Thomas; Kuffel, Thomas S.; Novicevic, Milorad M.; Keaton, Paul N.

    2006-01-01

    In this article, the authors' goal was to examine faculty roles from a role-theoretic perspective based on a typology of faculty categories. Based on an assessment of specific faculty needs within each category, the authors proposed a differentiated management model for academic deans to address specific segments of the faculty work environment.…

  8. 7 CFR 993.515 - Size categories.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Size categories. 993.515 Section 993.515 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... respective size categories expressed as follows or in an applicable equivalent range expressed in the...

  9. Conceptual Influences on Category-Based Induction

    ERIC Educational Resources Information Center

    Gelman, Susan A.; Davidson, Natalie S.

    2013-01-01

    One important function of categories is to permit rich inductive inferences. Prior work shows that children use category labels to guide their inductive inferences. However, there are competing theories to explain this phenomenon, differing in the roles attributed to conceptual information vs. perceptual similarity. Seven experiments with 4- to…

  10. Generalized Categorial Grammar for Unbounded Dependencies Recovery

    ERIC Educational Resources Information Center

    Nguyen, Luan Viet

    2014-01-01

    Accurate recovery of predicate-argument dependencies is vital for interpretation tasks like information extraction and question answering, and unbounded dependencies may account for a significant portion of the dependencies in any given text. This thesis describes a Generalized Categorial Grammar (GCG) which, like other categorial grammars,…

  11. Geometric Representation of Association between Categories

    ERIC Educational Resources Information Center

    Heiser, Willem J.

    2004-01-01

    Categories can be counted, rated, or ranked, but they cannot be measured. Likewise, persons or individuals can be counted, rated, or ranked, but they cannot be measured either. Nevertheless, psychology has realized early on that it can take an indirect road to measurement: What can be measured is the strength of association between categories in…

  12. 46 CFR 120.352 - Battery categories.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Battery categories. 120.352 Section 120.352 Shipping... and Distribution Systems § 120.352 Battery categories. This section applies to batteries installed to... sources of power to final emergency loads. (a) Large. A large battery installation is one connected to...

  13. 46 CFR 183.352 - Battery categories.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Battery categories. 183.352 Section 183.352 Shipping...) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.352 Battery categories. This section applies to batteries installed to meet the requirements of § 183.310 for secondary sources of power...

  14. 46 CFR 120.352 - Battery categories.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Battery categories. 120.352 Section 120.352 Shipping... and Distribution Systems § 120.352 Battery categories. This section applies to batteries installed to... sources of power to final emergency loads. (a) Large. A large battery installation is one connected to...

  15. 46 CFR 129.353 - Battery categories.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Battery categories. 129.353 Section 129.353 Shipping... INSTALLATIONS Power Sources and Distribution Systems § 129.353 Battery categories. This section applies to batteries installed to meet the requirements of § 129.310(a) for secondary sources of power to vital...

  16. 46 CFR 120.352 - Battery categories.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Battery categories. 120.352 Section 120.352 Shipping... and Distribution Systems § 120.352 Battery categories. This section applies to batteries installed to... sources of power to final emergency loads. (a) Large. A large battery installation is one connected to...

  17. 46 CFR 183.352 - Battery categories.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Battery categories. 183.352 Section 183.352 Shipping...) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.352 Battery categories. This section applies to batteries installed to meet the requirements of § 183.310 for secondary sources of power...

  18. 46 CFR 183.352 - Battery categories.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Battery categories. 183.352 Section 183.352 Shipping...) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.352 Battery categories. This section applies to batteries installed to meet the requirements of § 183.310 for secondary sources of power...

  19. 46 CFR 129.353 - Battery categories.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Battery categories. 129.353 Section 129.353 Shipping... INSTALLATIONS Power Sources and Distribution Systems § 129.353 Battery categories. This section applies to batteries installed to meet the requirements of § 129.310(a) for secondary sources of power to vital...

  20. 46 CFR 129.353 - Battery categories.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Battery categories. 129.353 Section 129.353 Shipping... INSTALLATIONS Power Sources and Distribution Systems § 129.353 Battery categories. This section applies to batteries installed to meet the requirements of § 129.310(a) for secondary sources of power to vital...

  1. 46 CFR 129.353 - Battery categories.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Battery categories. 129.353 Section 129.353 Shipping... INSTALLATIONS Power Sources and Distribution Systems § 129.353 Battery categories. This section applies to batteries installed to meet the requirements of § 129.310(a) for secondary sources of power to vital...

  2. 46 CFR 129.353 - Battery categories.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Battery categories. 129.353 Section 129.353 Shipping... INSTALLATIONS Power Sources and Distribution Systems § 129.353 Battery categories. This section applies to batteries installed to meet the requirements of § 129.310(a) for secondary sources of power to vital...

  3. 46 CFR 120.352 - Battery categories.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Battery categories. 120.352 Section 120.352 Shipping... and Distribution Systems § 120.352 Battery categories. This section applies to batteries installed to... sources of power to final emergency loads. (a) Large. A large battery installation is one connected to...

  4. 46 CFR 183.352 - Battery categories.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Battery categories. 183.352 Section 183.352 Shipping...) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.352 Battery categories. This section applies to batteries installed to meet the requirements of § 183.310 for secondary sources of power...

  5. 46 CFR 183.352 - Battery categories.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Battery categories. 183.352 Section 183.352 Shipping...) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.352 Battery categories. This section applies to batteries installed to meet the requirements of § 183.310 for secondary sources of power...

  6. 46 CFR 120.352 - Battery categories.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Battery categories. 120.352 Section 120.352 Shipping... and Distribution Systems § 120.352 Battery categories. This section applies to batteries installed to... sources of power to final emergency loads. (a) Large. A large battery installation is one connected to...

  7. Generalized Categorial Grammar for Unbounded Dependencies Recovery

    ERIC Educational Resources Information Center

    Nguyen, Luan Viet

    2014-01-01

    Accurate recovery of predicate-argument dependencies is vital for interpretation tasks like information extraction and question answering, and unbounded dependencies may account for a significant portion of the dependencies in any given text. This thesis describes a Generalized Categorial Grammar (GCG) which, like other categorial grammars,…

  8. Geometric Representation of Association between Categories

    ERIC Educational Resources Information Center

    Heiser, Willem J.

    2004-01-01

    Categories can be counted, rated, or ranked, but they cannot be measured. Likewise, persons or individuals can be counted, rated, or ranked, but they cannot be measured either. Nevertheless, psychology has realized early on that it can take an indirect road to measurement: What can be measured is the strength of association between categories in…

  9. Induction with cross-classified categories.

    PubMed

    Murphy, G L; Ross, B H

    1999-11-01

    One of the main functions of categories is to allow inferences about new objects. However, most objects are cross-classified, and it is not known whether and how people combine information from these different categories in making inferences. In six experiments, food categories, which are strongly cross-classified (e.g., a bagel is both a bread and a breakfast food), were studied. For each food, the subjects were told fictitious facts (e.g., 75% of breads are subject to spoilage from Aspergillus molds) about two of the categories to which it belonged and then were asked to make an inference about the food (e.g., how likely is a bagel to be subject to spoilage from Aspergillus molds?). We found no more use of multiple categories in these cases of cross-classification than in ambiguous classification, in which it is uncertain to which category an item belongs. However, some procedural manipulations did markedly increase the use of both categories in inferences, primarily those that focused the subjects' attention on the critical feature in both categories.

  10. 40 CFR 156.62 - Toxicity Category.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... REQUIREMENTS FOR PESTICIDES AND DEVICES Human Hazard and Precautionary Statements § 156.62 Toxicity Category... being the highest toxicity category. Most human hazard, precautionary statements, and human personal... days No corneal opacity; irritation reversible within 7 days No irritation Skin irritation Corrosive...

  11. SUSTAIN: A Network Model of Category Learning

    ERIC Educational Resources Information Center

    Love, Bradley C.; Medin, Douglas L.; Gureckis, Todd M.

    2004-01-01

    SUSTAIN (Supervised and Unsupervised STratified Adaptive Incremental Network) is a model of how humans learn categories from examples. SUSTAIN initially assumes a simple category structure. If simple solutions prove inadequate and SUSTAIN is confronted with a surprising event (e.g., it is told that a bat is a mammal instead of a bird), SUSTAIN…

  12. SUSTAIN: a network model of category learning.

    PubMed

    Love, Bradley C; Medin, Douglas L; Gureckis, Todd M

    2004-04-01

    SUSTAIN (Supervised and Unsupervised STratified Adaptive Incremental Network) is a model of how humans learn categories from examples. SUSTAIN initially assumes a simple category structure. If simple solutions prove inadequate and SUSTAIN is confronted with a surprising event (e.g., it is told that a bat is a mammal instead of a bird), SUSTAIN recruits an additional cluster to represent the surprising event. Newly recruited clusters are available to explain future events and can themselves evolve into prototypes-attractors-rules. SUSTAIN's discovery of category substructure is affected not only by the structure of the world but by the nature of the learning task and the learner's goals. SUSTAIN successfully extends category learning models to studies of inference learning, unsupervised learning, category construction, and contexts in which identification learning is faster than classification learning.

  13. Diagnostic Categories in Autobiographical Accounts of Illness.

    PubMed

    Kelly, Michael P

    2015-01-01

    Working within frameworks drawn from the writings of Immanuel Kant, Alfred Schutz, and Kenneth Burke, this article examines the role that diagnostic categories play in autobiographical accounts of illness, with a special focus on chronic disease. Four lay diagnostic categories, each with different connections to formal medical diagnostic categories, serve as typifications to make sense of the way the lifeworld changes over the course of chronic illness. These diagnostic categories are used in conjunction with another set of typifications: lay epidemiologies, lay etiologies, lay prognostics, and lay therapeutics. Together these serve to construct and reconstruct the self at the center of the lifeworld. Embedded within the lay diagnostic categories are narratives of progression, regression, or stability, forms of typification derived from literary and storytelling genres. These narratives are developed by the self in autobiographical accounts of illness.

  14. Pattern-induced covert category learning in songbirds

    PubMed Central

    Comins, Jordan A.; Gentner, Timothy Q.

    2015-01-01

    Summary Language is uniquely human, but its acquisition may involve cognitive capacities shared with other species [1-5]. During development, language experience alters speech sound (phoneme) categorization [6-8]. Newborn infants distinguish the phonemes in all languages, but by 10 months show adult-like greater sensitivity to native language phonemic contrasts than non-native contrasts [8, 9]. Distributional theories account for phonetic learning by positing that infants infer category boundaries from modal distributions of speech sounds along acoustic continua [10, 11]. For example, tokens of the sounds /b/ and /p/ cluster around different mean voice onset times. To disambiguate overlapping distributions, contextual theories propose that phonetic category learning is informed by higher-level patterns (e.g. words) in which phonemes normally occur [12-15]. For example, the vowel sounds /I/ and /e/ can occupy similar perceptual spaces, but can be distinguished in the context of “with” and “well”. Both distributional and contextual cues appear to function in speech acquisition [10-12, 16-21]. Non-human species also benefit from distributional cues for category learning [22-24], but whether category learning benefits from contextual information in non-human animals is unknown. The use of higher-level patterns to guide lower-level category learning may reflect uniquely human capacities tied to language acquisition, or more general learning abilities reflecting shared neurobiological mechanisms. Using songbirds, European starlings, we show that higher-level pattern learning covertly enhances categorization of the natural communication sounds. This observation mirrors the support for contextual theories of phonemic category learning in humans, and demonstrates a general form of learning not unique to humans or language. PMID:26119748

  15. Can height categories replace weight categories in striking martial arts competitions? A pilot study.

    PubMed

    Dubnov-Raz, Gal; Mashiach-Arazi, Yael; Nouriel, Ariella; Raz, Raanan; Constantini, Naama W

    2015-09-29

    In most combat sports and martial arts, athletes compete within weight categories. Disordered eating behaviors and intentional pre-competition rapid weight loss are commonly seen in this population, attributed to weight categorization. We examined if height categories can be used as an alternative to weight categories for competition, in order to protect the health of athletes. Height and weight of 169 child and adolescent competitive karate athletes were measured. Participants were divided into eleven hypothetical weight categories of 5 kg increments, and eleven hypothetical height categories of 5 cm increments. We calculated the coefficient of variation of height and weight by each division method. We also calculated how many participants fit into corresponding categories of both height and weight, and how many would shift a category if divided by height. There was a high correlation between height and weight (r = 0.91, p<0.001). The mean range of heights seen within current weight categories was reduced by 83% when participants were divided by height. When allocating athletes by height categories, 74% of athletes would shift up or down one weight category at most, compared with the current categorization method. We conclude that dividing young karate athletes by height categories significantly reduced the range of heights of competitors within the category. Such categorization would not cause athletes to compete against much heavier opponents in most cases. Using height categories as a means to reduce eating disorders in combat sports should be further examined.

  16. Can height categories replace weight categories in striking martial arts competitions? A pilot study

    PubMed Central

    Dubnov-Raz, Gal; Mashiach-Arazi, Yael; Nouriel, Ariella; Raz, Raanan; Constantini, Naama W.

    2015-01-01

    In most combat sports and martial arts, athletes compete within weight categories. Disordered eating behaviors and intentional pre-competition rapid weight loss are commonly seen in this population, attributed to weight categorization. We examined if height categories can be used as an alternative to weight categories for competition, in order to protect the health of athletes. Height and weight of 169 child and adolescent competitive karate athletes were measured. Participants were divided into eleven hypothetical weight categories of 5 kg increments, and eleven hypothetical height categories of 5 cm increments. We calculated the coefficient of variation of height and weight by each division method. We also calculated how many participants fit into corresponding categories of both height and weight, and how many would shift a category if divided by height. There was a high correlation between height and weight (r = 0.91, p<0.001). The mean range of heights seen within current weight categories was reduced by 83% when participants were divided by height. When allocating athletes by height categories, 74% of athletes would shift up or down one weight category at most, compared with the current categorization method. We conclude that dividing young karate athletes by height categories significantly reduced the range of heights of competitors within the category. Such categorization would not cause athletes to compete against much heavier opponents in most cases. Using height categories as a means to reduce eating disorders in combat sports should be further examined. PMID:26557193

  17. Prolonged Attenuation of Amygdala-Kindled Seizure Measures in Rats by Convection-Enhanced Delivery of the N-Type Calcium Channel Antagonists ω-Conotoxin GVIA and ω-Conotoxin MVIIA

    PubMed Central

    Gasior, Maciej; White, Natalie A.; Rogawski, Michael A.

    2008-01-01

    Convection-enhanced delivery (CED) permits the homogeneous distribution of therapeutic agents throughout localized regions of the brain parenchyma without causing tissue damage as occurs with bolus injection. Here, we examined whether CED infusion of the N-type calcium channel antagonists ω-conotoxin GVIA (ω-CTX-G) and ω-conotoxin MVIIA (ω-CTX-M) can attenuate kindling measures in fully amygdala-kindled rats. Rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully kindled animals received infusions of vehicle, ω-CTX-G (0.005, 0.05, and 0.5 nmol), ω-CTX-M (0.05, 0.15, and 0.5 nmol), proteolytically inactivated ω-CTX-M (0.5 nmol), or carbamazepine (500 nmol) into the stimulation site. CED of ω-CTX-G and ω-CTX-M over a 20-min period resulted in a dose-dependent increase in the afterdischarge threshold and a decrease in the afterdischarge duration and behavioral seizure score and duration during a period of 20 min to 1 week after the infusion, indicating an inhibitory effect on the triggering and expression of kindled seizures. The protective effects of ω-conotoxins reached a maximum at 48 h postinfusion, and then they gradually resolved over the next 5 days. In contrast, carbamazepine was active at 20 min but not at 24 h after the infusion, whereas CED of vehicle or inactivated ω-CTX-M had no effect. Except for transient tremor in some rats receiving the highest toxin doses, no adverse effects were observed. These results indicate that local CED of high-molecular-weight presynaptic N-type calcium channel blockers can produce long-lasting inhibition of brain excitability and that they may provide prolonged seizure protection in focal seizure disorders. PMID:17717191

  18. Observation versus classification in supervised category learning.

    PubMed

    Levering, Kimery R; Kurtz, Kenneth J

    2015-02-01

    The traditional supervised classification paradigm encourages learners to acquire only the knowledge needed to predict category membership (a discriminative approach). An alternative that aligns with important aspects of real-world concept formation is learning with a broader focus to acquire knowledge of the internal structure of each category (a generative approach). Our work addresses the impact of a particular component of the traditional classification task: the guess-and-correct cycle. We compare classification learning to a supervised observational learning task in which learners are shown labeled examples but make no classification response. The goals of this work sit at two levels: (1) testing for differences in the nature of the category representations that arise from two basic learning modes; and (2) evaluating the generative/discriminative continuum as a theoretical tool for understand learning modes and their outcomes. Specifically, we view the guess-and-correct cycle as consistent with a more discriminative approach and therefore expected it to lead to narrower category knowledge. Across two experiments, the observational mode led to greater sensitivity to distributional properties of features and correlations between features. We conclude that a relatively subtle procedural difference in supervised category learning substantially impacts what learners come to know about the categories. The results demonstrate the value of the generative/discriminative continuum as a tool for advancing the psychology of category learning and also provide a valuable constraint for formal models and associated theories.

  19. Altered Implicit Category Learning in Anorexia Nervosa

    PubMed Central

    Shott, Megan E.; Filoteo, J. Vincent; Jappe, Leah M.; Pryor, Tamara; Maddox, W. Todd; Rollin, Michael D.H.; Hagman, Jennifer O.; Frank, Guido K.W.

    2012-01-01

    Objective Recent research has identified specific cognitive deficits in patients with anorexia nervosa (AN), including impairment in executive functioning and attention. Another such cognitive process, implicit category learning has been less studied in AN. This study examined whether implicit category learning is impaired in AN. Method Twenty-one women diagnosed with AN and 19 control women (CW) were administered an implicit category learning task in which they were asked to categorize simple perceptual stimuli (Gabor patches) into one of two categories. Category membership was based on a linear integration (i.e., an implicit task) of two stimulus dimensions (orientation and spatial frequency of the stimulus). Results AN individuals were less accurate on implicit category learning relative to age-matched CW. Model-based analyses indicated that, even when AN individuals used the appropriate (i.e., implicit) strategy they were still impaired relative to CW who also used the same strategy. In addition, task performance in AN patients was worse the higher they were in self-reported novelty seeking and the lower they were in sensitivity to punishment. Conclusions These results indicate that AN patients have implicit category learning deficits, and given this type of learning is thought to be mediated by striatal dopamine pathways, AN patients may have deficits in these neural systems. The finding of significant correlations with novelty seeking and sensitivity to punishment suggests that feedback sensitivity is related to implicit learning in AN. PMID:22201300

  20. Intra-Myocardial Injection of Both Growth Factors and Heart Derived Sca-1+/CD31− Cells Attenuates Post-MI LV Remodeling More Than Does Cell Transplantation Alone: Neither Intervention Enhances Functionally Significant Cardiomyocyte Regeneration

    PubMed Central

    Wang, Xiaohong; Li, Qinglu; Hu, Qingsong; Suntharalingam, Piradeep; From, Arthur H. L.; Zhang, Jianyi

    2014-01-01

    Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are two potent cell survival and regenerative factors in response to myocardial injury (MI). We hypothesized that simultaneous delivery of IGF+HGF combined with Sca-1+/CD31− cells would improve the outcome of transplantation therapy in response to the altered hostile microenvironment post MI. One million adenovirus nuclear LacZ-labeled Sca-1+/CD31− cells were injected into the peri-infarction area after left anterior descending coronary artery (LAD) ligation in mice. Recombinant mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left ventricular (LV) function was assessed by echocardiography 4 weeks after the transplantation. The cell engraftment, differentiation and cardiomyocyte regeneration were evaluated by histological analysis. Sca-1+/CD31− cells formed viable grafts and improved LV ejection fraction (EF) (Control, 54.5+/−2.4; MI, 17.6+/−3.1; Cell, 28.2+/−4.2, n = 9, P<0.01). IGF+HGF significantly enhanced the benefits of cell transplantation as evidenced by increased EF (38.8+/−2.2; n = 9, P<0.01) and attenuated adverse structural remodeling. Furthermore, IGF+HGF supplementation increased the cell engraftment rate, promoted the transplanted cell survival, enhanced angiogenesis, and minimally stimulated endogenous cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF treatment stimulated Sca-1+/CD31− cell proliferation and inhibited serum free medium induced apoptosis. Supperarray profiling of Sca-1+/CD31− cells revealed that Sca-1+/CD31− cells highly expressed various trophic factor mRNAs and IGF+HGF treatment altered the mRNAs expression patterns of these cells. These data indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial repair by stimulating donor cell and endogenous cardiac stem cell survival, regeneration and promoting angiogenesis. PMID:24919180

  1. The impact of category structure and training methodology on learning and generalizing within-category representations.

    PubMed

    Ell, Shawn W; Smith, David B; Peralta, Gabriela; Hélie, Sébastien

    2017-08-01

    When interacting with categories, representations focused on within-category relationships are often learned, but the conditions promoting within-category representations and their generalizability are unclear. We report the results of three experiments investigating the impact of category structure and training methodology on the learning and generalization of within-category representations (i.e., correlational structure). Participants were trained on either rule-based or information-integration structures using classification (Is the stimulus a member of Category A or Category B?), concept (e.g., Is the stimulus a member of Category A, Yes or No?), or inference (infer the missing component of the stimulus from a given category) and then tested on either an inference task (Experiments 1 and 2) or a classification task (Experiment 3). For the information-integration structure, within-category representations were consistently learned, could be generalized to novel stimuli, and could be generalized to support inference at test. For the rule-based structure, extended inference training resulted in generalization to novel stimuli (Experiment 2) and inference training resulted in generalization to classification (Experiment 3). These data help to clarify the conditions under which within-category representations can be learned. Moreover, these results make an important contribution in highlighting the impact of category structure and training methodology on the generalization of categorical knowledge.

  2. God's Categories: The Effect of Religiosity on Children's Teleological and Essentialist Beliefs about Categories

    ERIC Educational Resources Information Center

    Diesendruck, Gil; Haber, Lital

    2009-01-01

    Creationism implies that God imbued each category with a unique nature and purpose. These implications closely correspond to what some cognitive psychologists define as an essentialistic and teleological stance towards categories. This study assessed to what extent the belief in God as creator of categories is related to the mappings of these…

  3. God's Categories: The Effect of Religiosity on Children's Teleological and Essentialist Beliefs about Categories

    ERIC Educational Resources Information Center

    Diesendruck, Gil; Haber, Lital

    2009-01-01

    Creationism implies that God imbued each category with a unique nature and purpose. These implications closely correspond to what some cognitive psychologists define as an essentialistic and teleological stance towards categories. This study assessed to what extent the belief in God as creator of categories is related to the mappings of these…

  4. Study preferences for exemplar variability in self-regulated category learning.

    PubMed

    Wahlheim, Christopher N; DeSoto, K Andrew

    2017-02-01

    Increasing exemplar variability during category learning can enhance classification of novel exemplars from studied categories. Four experiments examined whether participants preferred variability when making study choices with the goal of later classifying novel exemplars. In Experiments 1-3, participants were familiarised with exemplars of birds from multiple categories prior to making category-level assessments of learning and subsequent choices about whether to receive more variability or repetitions of exemplars during study. After study, participants classified novel exemplars from studied categories. The majority of participants showed a consistent preference for variability in their study, but choices were not related to category-level assessments of learning. Experiment 4 provided evidence that study preferences were based primarily on theoretical beliefs in that most participants indicated a preference for variability on questionnaires that did not include prior experience with exemplars. Potential directions for theoretical development and applications to education are discussed.

  5. Vortex attenuation flight experiments

    NASA Technical Reports Server (NTRS)

    Barber, M. R.; Hastings, E. C., Jr.; Champine, R. A.; Tymczyszyn, J. J.

    1977-01-01

    Flight tests evaluating the effects of altered span loading, turbulence ingestion, combinations of mass and turbulence ingestion, and combinations of altered span loading turbulance ingestion on trailed wake vortex attenuation were conducted. Span loadings were altered in flight by varying the deflections of the inboard and outboard flaps on a B-747 aircraft. Turbulence ingestion was achieved in flight by mounting splines on a C-54G aircraft. Mass and turbulence ingestion was achieved in flight by varying the thrust on the B-747 aircraft. Combinations of altered span loading and turbulence ingestion were achieved in flight by installing a spoiler on a CV-990 aircraft and by deflecting the existing spoilers on a B-747 aircraft. The characteristics of the attenuated and unattenuated vortexes were determined by probing them with smaller aircraft. Acceptable separation distances for encounters with the attenuated and unattenuated vortexes are presented.

  6. NASA Scope and Subject Category Guide

    NASA Technical Reports Server (NTRS)

    2011-01-01

    This guide provides a simple, effective tool to assist aerospace information analysts and database builders in the high-level subject classification of technical materials. Each of the 76 subject categories comprising the classification scheme is presented with a description of category scope, a listing of subtopics, cross references, and an indication of particular areas of NASA interest. The guide also includes an index of nearly 3,000 specific research topics cross referenced to the subject categories. The portable document format (PDF) version of the guide contains links in the index from each input subject to its corresponding categories. In addition to subject classification, the guide can serve as an aid to searching databases that use the classification scheme, and is also an excellent selection guide for those involved in the acquisition of aerospace literature. The CD-ROM contains both HTML and PDF versions.

  7. On Gauging Symmetry of Modular Categories

    NASA Astrophysics Data System (ADS)

    Cui, Shawn X.; Galindo, César; Plavnik, Julia Yael; Wang, Zhenghan

    2016-12-01

    Topological order of a topological phase of matter in two spacial dimensions is encoded by a unitary modular (tensor) category (UMC). A group symmetry of the topological phase induces a group symmetry of its corresponding UMC. Gauging is a well-known theoretical tool to promote a global symmetry to a local gauge symmetry. We give a mathematical formulation of gauging in terms of higher category formalism. Roughly, given a UMC with a symmetry group G, gauging is a 2-step process: first extend the UMC to a G-crossed braided fusion category and then take the equivariantization of the resulting category. Gauging can tell whether or not two enriched topological phases of matter are different, and also provides a way to construct new UMCs out of old ones. We derive a formula for the {H^4}-obstruction, prove some properties of gauging, and carry out gauging for two concrete examples.

  8. Human category learning 2.0.

    PubMed

    Ashby, F Gregory; Maddox, W Todd

    2011-04-01

    During the 1990s and early 2000s, cognitive neuroscience investigations of human category learning focused on the primary goal of showing that humans have multiple category-learning systems and on the secondary goals of identifying key qualitative properties of each system and of roughly mapping out the neural networks that mediate each system. Many researchers now accept the strength of the evidence supporting multiple systems, and as a result, during the past few years, work has begun on the second generation of research questions-that is, on questions that begin with the assumption that humans have multiple category-learning systems. This article reviews much of this second generation of research. Topics covered include (1) How do the various systems interact? (2) Are there different neural systems for categorization and category representation? (3) How does automaticity develop in each system? and (4) Exactly how does each system learn?

  9. 40 CFR 156.62 - Toxicity Category.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... distributed. In addition, toxicity categories may be used for regulatory purposes other than labeling, such as... days No corneal opacity; irritation reversible within 7 days No irritation Skin irritation Corrosive...

  10. 40 CFR 156.62 - Toxicity Category.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... distributed. In addition, toxicity categories may be used for regulatory purposes other than labeling, such as... days No corneal opacity; irritation reversible within 7 days No irritation Skin irritation Corrosive...

  11. Words can slow down category learning.

    PubMed

    Brojde, Chandra L; Porter, Chelsea; Colunga, Eliana

    2011-08-01

    Words have been shown to influence many cognitive tasks, including category learning. Most demonstrations of these effects have focused on instances in which words facilitate performance. One possibility is that words augment representations, predicting an across the-board benefit of words during category learning. We propose that words shift attention to dimensions that have been historically predictive in similar contexts. Under this account, there should be cases in which words are detrimental to performance. The results from two experiments show that words impair learning of object categories under some conditions. Experiment 1 shows that words hurt performance when learning to categorize by texture. Experiment 2 shows that words also hurt when learning to categorize by brightness, leading to selectively attending to shape when both shape and hue could be used to correctly categorize stimuli. We suggest that both the positive and negative effects of words have developmental origins in the history of word usage while learning categories. [corrected

  12. Clinical expertise and reasoning with uncertain categories.

    PubMed

    Hayes, Brett K; Chen, Tsan-Hsiang Jessamine

    2008-10-01

    Expert clinical psychologists, clinical psychology graduates, and nonclinical graduate students were presented with clinical and nonclinical cases in which the diagnosis or category membership of a character was uncertain; they then made feature predictions about the character. For each case, there was a diagnosis or category that was highly probable and a less likely alternative that either did (relevant condition) or did not (neutral condition) alter predictions. For clinical cases, clinical experts and graduate clinicians gave different predictions for the relevant and neutral conditions, indicating that they had considered the uncertain nature of the diagnosis in their predictions. Although they acknowledged that the diagnosis was uncertain, nonclinical students ignored the less likely diagnostic alternatives when making predictions. For the nonclinical cases, all three groups made predictions based on only the most likely category alternative. The results showed that clinical training and/or experience promote multiple-category reasoning, but that this effect is domain specific.

  13. Searching for Category-Consistent Features: A Computational Approach to Understanding Visual Category Representation.

    PubMed

    Yu, Chen-Ping; Maxfield, Justin T; Zelinsky, Gregory J

    2016-06-01

    This article introduces a generative model of category representation that uses computer vision methods to extract category-consistent features (CCFs) directly from images of category exemplars. The model was trained on 4,800 images of common objects, and CCFs were obtained for 68 categories spanning subordinate, basic, and superordinate levels in a category hierarchy. When participants searched for these same categories, targets cued at the subordinate level were preferentially fixated, but fixated targets were verified faster when they followed a basic-level cue. The subordinate-level advantage in guidance is explained by the number of target-category CCFs, a measure of category specificity that decreases with movement up the category hierarchy. The basic-level advantage in verification is explained by multiplying the number of CCFs by sibling distance, a measure of category distinctiveness. With this model, the visual representations of real-world object categories, each learned from the vast numbers of image exemplars accumulated throughout everyday experience, can finally be studied.

  14. Feature-based versus category-based induction with uncertain categories.

    PubMed

    Griffiths, Oren; Hayes, Brett K; Newell, Ben R

    2012-05-01

    Previous research has suggested that when feature inferences have to be made about an instance whose category membership is uncertain, feature-based inductive reasoning is used to the exclusion of category-based induction. These results contrast with the observation that people can and do use category-based induction when category membership is known. The present experiments examined the conditions that drive feature-based and category-based strategies in induction under category uncertainty. Specifically, 2 experiments investigated whether reliance on feature-based inductive strategies is a product of the lack of coherence in the categories used in previous research or is due to the use of a decision-only induction procedure. Experiment 1 found that feature-based reasoning remained the preferred strategy even when categories with relatively high internal coherence were used. Experiment 2 found a shift toward category-based reasoning when participants were trained to classify category members prior to feature induction. Together, these results suggest that an appropriate conceptual representation must be formed through experience with a category before it is likely to be used as a basis for feature induction.

  15. Comparing two K-category assignments by a K-category correlation coefficient.

    PubMed

    Gorodkin, J

    2004-12-01

    Predicted assignments of biological sequences are often evaluated by Matthews correlation coefficient. However, Matthews correlation coefficient applies only to cases where the assignments belong to two categories, and cases with more than two categories are often artificially forced into two categories by considering what belongs and what does not belong to one of the categories, leading to the loss of information. Here, an extended correlation coefficient that applies to K-categories is proposed, and this measure is shown to be highly applicable for evaluating prediction of RNA secondary structure in cases where some predicted pairs go into the category "unknown" due to lack of reliability in predicted pairs or unpaired residues. Hence, predicting base pairs of RNA secondary structure can be a three-category problem. The measure is further shown to be well in agreement with existing performance measures used for ranking protein secondary structure predictions. Server and software is available at http://rk.kvl.dk/.

  16. Derivation of plutonium-239 materials disposition categories

    SciTech Connect

    Brough, W.G.

    1995-04-27

    At this time, the Office of Fissile Materials Disposition within the DOE, is assessing alternatives for the disposition of excess fissile materials. To facilitate the assessment, the Plutonium-Bearing Materials Feed Report for the DOE Fissile Materials Disposition Program Alternatives report was written. The development of the material categories and the derivation of the inventory quantities associated with those categories is documented in this report.

  17. Ultrasound attenuation in ferrofluids.

    PubMed

    Shliomis, Mark; Mond, Michael; Morozov, Konstantin

    2008-08-15

    The absorption of acoustic energy by internal degrees of freedom of short chains is proposed as a new viable mechanism of ultrasound attenuation in ferrofluids. It is demonstrated that even though the volume fraction of the chains may be quite small, such an effect may reach the order of magnitude of viscous damping. In addition, by investigating the statistical properties of dimers in ferrofluids, it is shown that an applied magnetic field modifies the sound attenuation in a highly anisotropic manner. The proposed mechanism provides new insight into the fundamental issue of colloidal response, and, in particular, may lead to its utilization in novel experimental concepts.

  18. On the flexibility of phonetic categories

    NASA Astrophysics Data System (ADS)

    Francis, Alexander L.; Nusbaum, Howard C.

    2002-05-01

    Research on phonetic category acquisition suggests that over the course of development children shift the relative weight given to various acoustic cues to particular phonetic categories [S. Nittrouer, J. Phon. 20, 1-32 (1992)]. Adults also show flexibility in acquiring second language categories and learning to recognize synthetic speech. In both cases listeners must shift attention among some acoustic cues and change the weighting and mapping of others. Recent research demonstrated that category-level feedback can induce adult listeners to shift attention between conflicting cues to native stop-consonant categories. Subsequent research showed that adult listeners also reorganize the distribution of their attention to acoustic cues in learning to better understand synthetic speech. Moreover, research on learning foreign phonetic contrasts suggests that listeners can learn to direct attention to unfamiliar acoustic cues. These results suggest that phonetic categories are flexible in terms of the nature and quality of the acoustic cues that define them. We argue that this flexibility is a consequence of the basic nature of the general mechanism that mediates speech perception: In order to resolve the problem of context-conditioned variability, listeners must dynamically modify attention to the acoustic signal in a context-dependent manner.

  19. Learning, retention, and generalization of haptic categories

    NASA Astrophysics Data System (ADS)

    Do, Phuong T.

    This dissertation explored how haptic concepts are learned, retained, and generalized to the same or different modality. Participants learned to classify objects into three categories either visually or haptically via different training procedures, followed by an immediate or delayed transfer test. Experiment I involved visual versus haptic learning and transfer. Intermodal matching between vision and haptics was investigated in Experiment II. Experiments III and IV examined intersensory conflict in within- and between-category bimodal situations to determine the degree of perceptual dominance between sight and touch. Experiment V explored the intramodal relationship between similarity and categorization in a psychological space, as revealed by MDS analysis of similarity judgments. Major findings were: (1) visual examination resulted in relatively higher performance accuracy than haptic learning; (2) systematic training produced better category learning of haptic concepts across all modality conditions; (3) the category prototypes were rated newer than any transfer stimulus followed learning both immediately and after a week delay; and, (4) although they converged at the apex of two transformational trajectories, the category prototypes became more central to their respective categories and increasingly structured as a function of learning. Implications for theories of multimodal similarity and categorization behavior are discussed in terms of discrimination learning, sensory integration, and dominance relation.

  20. N400 and category exemplar associative strength.

    PubMed

    Núñez-Peña, M Isabel; Honrubia-Serrano, M Luisa

    2005-04-01

    The main purpose of this study was to examine if the N400 amplitude can be considered an index of category exemplar strength of association in a semantic categorization task. Series of six words from a particular semantic category were used as context, and the strength of association between the seventh word and the category was manipulated. Moreover, subjects were asked to perform two different tasks: one consisting of reading the words for comprehension and the other of making a decision regarding the congruence of the ending word. Results showed that the N400 component was elicited by whichever word that was not the best exemplar for the category (atypical members and nonmember of the category). No interaction between type of ending word and type of task was found around 400 ms poststimuli although the P3b component was present for infrequent stimuli in the decision task. It is concluded that the N400 amplitude is sensitive to category membership although no specific attention to the semantic relationship between words was required.

  1. Uncertainty in Category-Based Induction: When Do People Integrate Across Categories?

    PubMed Central

    Murphy, Gregory L; Ross, Brian H

    2010-01-01

    Two experiments investigated how people perform category-based induction for items that have uncertain categorization. Whereas normative considerations suggest that people should consider multiple relevant categories, much past research has argued that people focus on only the most likely category. A new method is introduced in which individual trials can be classified as using single or multiple categories, improving on past methods that relied on null effects as evidence for single-category use. Experiment 1 found that people did use multiple categories when the most likely category gave an ambiguous induction but that few people did so when it gave an unambiguous induction. Experiment 2 suggested that the reluctance to use multiple categories arose from a cognitive short-cut, in which only one source of information is consulted. The experiments found significant individual differences, suggesting that use of multiple categories is one of a number of strategies that can be used, rather than being the basis for most category-based induction. PMID:20192530

  2. Typicality Mediates Performance during Category Verification in Both Ad-hoc and Well-defined Categories

    PubMed Central

    Sandberg, Chaleece; Sebastian, Rajani; Kiran, Swathi

    2012-01-01

    Background The typicality effect is present in neurologically intact populations for natural, ad-hoc, and well-defined categories. Although sparse, there is evidence of typicality effects in persons with chronic stroke aphasia for natural and ad-hoc categories. However, it is unknown exactly what influences the typicality effect in this population. Aims The present study explores the possible contributors to the typicality effect in persons with aphasia by analyzing and comparing data from both normal and language-disordered populations, from persons with aphasia with more semantic impairment versus those with less semantic impairment, and from two types of categories with very different boundary structure (ad-hoc vs. well-defined). Methods and procedures A total of 40 neurologically healthy adults (20 older, 20 younger) and 35 persons with aphasia (20 LSI (less-semantically impaired) patients, 15 MSI (more-semantically impaired) patients) participated in the study. Participants completed one of two tasks: either category verification for ad-hoc categories or category verification for well-defined categories. Outcomes and Results Neurologically healthy participants showed typicality effects for both ad-hoc and well-defined categories. MSI patients showed a typicality effect for well-defined categories, but not for ad-hoc categories, whereas LSI patients showed a typicality effect for ad-hoc categories, but not for well-defined categories. Conclusions These results suggest that the degree of semantic impairment mediates the typicality effect in persons with aphasia depending on the structure of the category. PMID:22261305

  3. Tritium Attenuation by Distillation

    SciTech Connect

    Wittman, N.E.

    2001-07-31

    The objective of this study was to determine how a 100 Area distillation system could be used to reduce to a satisfactory low value the tritium content of the dilute moderator produced in the 100 Area stills, and whether such a tritium attenuator would have sufficient capacity to process all this material before it is sent to the 400 Area for reprocessing.

  4. Brucellosis: the case for live, attenuated vaccines.

    PubMed

    Ficht, Thomas A; Kahl-McDonagh, Melissa M; Arenas-Gamboa, Angela M; Rice-Ficht, Allison C

    2009-11-05

    The successful control of animal brucellosis and associated reduction in human exposure has limited the development of human brucellosis vaccines. However, the potential use of Brucella in bioterrorism or biowarfare suggests that direct intervention strategies are warranted. Although the dominant approach has explored the use of live attenuated vaccines, side effects associated with their use has prevented widespread use in humans. Development of live, attenuated Brucella vaccines that are safe for use in humans has focused on the deletion of important genes required for survival. However, the enhanced safety of deletion mutants is most often associated with reduced efficacy. For this reason recent efforts have sought to combine the optimal features of a attenuated live vaccine that is safe, free of side effects and efficacious in humans with enhanced immune stimulation through microencapsulation. The competitive advantages and innovations of this approach are: (1) use of highly attenuated, safe, gene knockout, live Brucella mutants; (2) manufacturing with unique disposable closed system technologies, and (3) oral/intranasal delivery in a novel microencapsulation-mediated controlled release formula to optimally provide the long term mucosal immunostimulation required for protective immunity. Based upon preliminary data, it is postulated that such vaccine delivery systems can be storage stable, administered orally or intranasally, and generally applicable to a number of agents.

  5. Practitioner perceptions of attenuated psychosis syndrome.

    PubMed

    Jacobs, Elizabeth; Kline, Emily; Schiffman, Jason

    2011-09-01

    The "Attenuated Psychosis Syndrome" (APS, sometimes referred to as the "schizophrenia prodrome") is characterized by subthreshold psychotic-like symptoms and functional decline, and is often associated with significant disability. These symptoms may cause impairment and are of further interest due to their predictive relation to schizophrenia and other psychotic disorders. These symptoms currently are not represented in the diagnostic system for mental health, and it is unclear how they are conceptualized by relevant professionals. The current study surveyed a national sample (n=303) of clinical psychologists, psychiatrists, and general practitioners regarding their clinical appraisal of APS. Practitioners were asked to respond to vignettes representing three conditions: psychosis, subthreshold psychosis (indicating 'attenuated' psychosis symptoms), and no psychotic symptoms. Practitioners' responses suggested that APS is viewed consistently with a DSM-IV-TR defined mental disorder and that most clinicians may diagnose this condition as a full threshold psychotic disorder. Findings tentatively suggest that the inclusion of an attenuated psychosis symptoms category in the forthcoming DSM-5 may be helpful in improving diagnostic reliability and facilitating best practice among community practitioners.

  6. Error Discounting in Probabilistic Category Learning

    ERIC Educational Resources Information Center

    Craig, Stewart; Lewandowsky, Stephan; Little, Daniel R.

    2011-01-01

    The assumption in some current theories of probabilistic categorization is that people gradually attenuate their learning in response to unavoidable error. However, existing evidence for this error discounting is sparse and open to alternative interpretations. We report 2 probabilistic-categorization experiments in which we investigated error…

  7. From Perceptual Categories to Concepts: What Develops?

    PubMed Central

    Sloutsky, Vladimir M.

    2010-01-01

    People are remarkably smart: they use language, possess complex motor skills, make non-trivial inferences, develop and use scientific theories, make laws, and adapt to complex dynamic environments. Much of this knowledge requires concepts and this paper focuses on how people acquire concepts. It is argued that conceptual development progresses from simple perceptual grouping to highly abstract scientific concepts. This proposal of conceptual development has four parts. First, it is argued that categories in the world have different structure. Second, there might be different learning systems (sub-served by different brain mechanisms) that evolved to learn categories of differing structures. Third, these systems exhibit differential maturational course, which affects how categories of different structures are learned in the course of development. And finally, an interaction of these components may result in the developmental transition from perceptual groupings to more abstract concepts. This paper reviews a large body of empirical evidence supporting this proposal. PMID:21116483

  8. Differentiation in preschooler's categories of emotion.

    PubMed

    Widen, Sherri C; Russell, James A

    2010-10-01

    Two studies (N = 68, ages 2;0-3;11; N = 80, ages 2;6-4;11) explore the idea that, rather than starting with a separate mental category for each discrete emotion, children start with two broad categories (positive and negative) and then differentiate within each until adult-like categories form. Children generated emotion labels for (a) facial expressions or (b) stories about an emotion's cause and consequence. Emotions included were happiness, anger, fear, sadness, and disgust. Both conditions yielded the predicted pattern of differentiation. These studies of younger children found the face more powerful in eliciting correct emotion labels than had prior research, which typically relied on older preschoolers. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  9. Multimedia category preferences of working engineers

    NASA Astrophysics Data System (ADS)

    Baukal, Charles E.; Ausburn, Lynna J.

    2016-09-01

    Many have argued for the importance of continuing engineering education (CEE), but relatively few recommendations were found in the literature for how to use multimedia technologies to deliver it most effectively. The study reported here addressed this gap by investigating the multimedia category preferences of working engineers. Four categories of multimedia, with two types in each category, were studied: verbal (text and narration), static graphics (drawing and photograph), dynamic non-interactive graphics (animation and video), and dynamic interactive graphics (simulated virtual reality (VR) and photo-real VR). The results showed that working engineers strongly preferred text over narration and somewhat preferred drawing over photograph, animation over video, and simulated VR over photo-real VR. These results suggest that a variety of multimedia types should be used in the instructional design of CEE content.

  10. Concepts and categories: a cognitive neuropsychological perspective.

    PubMed

    Mahon, Bradford Z; Caramazza, Alfonso

    2009-01-01

    One of the most provocative and exciting issues in cognitive science is how neural specificity for semantic categories of common objects arises in the functional architecture of the brain. More than two decades of research on the neuropsychological phenomenon of category-specific semantic deficits has generated detailed claims about the organization and representation of conceptual knowledge. More recently, researchers have sought to test hypotheses developed on the basis of neuropsychological evidence with functional imaging. From those two fields, the empirical generalization emerges that object domain and sensory modality jointly constrain the organization of knowledge in the brain. At the same time, research within the embodied cognition framework has highlighted the need to articulate how information is communicated between the sensory and motor systems, and processes that represent and generalize abstract information. Those developments point toward a new approach for understanding category specificity in terms of the coordinated influences of diverse regions and cognitive systems.

  11. Children's internal organization of locative categories.

    PubMed

    Erreich, A; Valian, V

    1979-12-01

    4 locative categories were investigated to determine whether their examples were organized according to the prototype/nonprototype distinction. A ranking task was presented to 30 adult subjects to see whether they would judge those instances which had been designated as prototypes by the experimenter to be the best exemplars of each category. An elicited-drawing task was administered to see whether there was a preference for drawing adult-designated prototypical instances. A matching task was presented to determine whether fewer errors would occur in response to adult-designated prototypical instances. The latter 2 tasks were presented to 4-year-olds, 6-year-olds, and adults, with 17 subjects in each group. The results provide strong evidence of prototype/nonprototype organization in 3 of the locative categories and weak evidence in the fourth. Tentative conclusions regarding the development of such organization are drawn.

  12. Moduli of linear and abelian categories

    NASA Astrophysics Data System (ADS)

    Anel, Mathieu

    2006-07-01

    Linear categories naturally have several identification relations : isomorphisms, categorical equivalences and Morita equivalences. In this thesis, we construct the classifying stacks for these three relations (\\ukcatiso, \\ukcateq, \\ukcatmor) together with the classifying stack of abelian categories (\\ukab), the originality of the subject being that, apart from the first one, these are higher stacks. The principal result is that, under some finiteness assumptions, these stacks are geometric in the sense of C. Simpson. In particular, one recover the Hochschild cohomology of a category C as the tangent complex, i.e. the object classifying first order deformations of C, of these stacks at the point defined by C. Moreover, there exists a natural sequence of surjective morphisms of stacks : \\ukcatiso tto \\ukcateq tto \\ukcatmor tto \\ukab for which we prove that the middle one is etale, and the right one is an equivalence.

  13. A compact rotary vane attenuator

    NASA Technical Reports Server (NTRS)

    Nixon, D. L.; Otosh, T. Y.; Stelzried, C. T.

    1969-01-01

    Rotary vane attenuator, when used as a front end attenuator, introduces an insertion loss that is proportional to the angle of rotation. New technique allows the construction of a shortened compact unit suitable for most installations.

  14. Derived Categories and Zero-Brane Stability

    SciTech Connect

    Lawrence, Albion

    2001-07-25

    We define a particular class of topological field theories associated to open strings and prove the resulting D-branes and open strings form the bounded derived category of coherent sheaves. This derivation is a variant of some ideas proposed recently by Douglas. We then argue that any 0-brane on any Calabi-Yau threefold must become unstable along some path in the Kahler moduli space. As a byproduct of this analysis we see how the derived category can be invariant under a birational transformation.

  15. Occipitotemporal Category Representations Are Sensitive to Abstract Category Boundaries Defined by Generalization Demands.

    PubMed

    Braunlich, Kurt; Liu, Zhiya; Seger, Carol A

    2017-08-09

    Categorization involves organizing perceptual information so as to maximize differences along dimensions that predict class membership while minimizing differences along dimensions that do not. In the current experiment, we investigated how neural representations reflecting learned category structure vary according to generalization demands. We asked male and female human participants to switch between two rules when determining whether stimuli should be considered members of a single known category. When categorizing according to the "strict" rule, participants were required to limit generalization to make fine-grained distinctions between stimuli and the category prototype. When categorizing according to the "lax" rule, participants were required to generalize category knowledge to highly atypical category members. As expected, frontoparietal regions were primarily sensitive to decisional demands (i.e., the distance of each stimulus from the active category boundary), whereas occipitotemporal representations were primarily sensitive to stimulus typicality (i.e., the similarity between each exemplar and the category prototype). Interestingly, occipitotemporal representations of stimulus typicality differed between rules. While decoding models were able to predict unseen data when trained and tested on the same rule, they were unable to do so when trained and tested on different rules. We additionally found that the discriminability of the multivariate signal negatively covaried with distance from the active category boundary. Thus, whereas many accounts of occipitotemporal cortex emphasize its important role in transforming visual information to accentuate learned category structure, our results highlight the flexible nature of these representations with regards to transient decisional demands.SIGNIFICANCE STATEMENT Occipitotemporal representations are known to reflect category structure and are often assumed to be largely invariant with regards to transient

  16. Category number impacts rule-based and information-integration category learning: a reassessment of evidence for dissociable category-learning systems.

    PubMed

    Stanton, Roger D; Nosofsky, Robert M

    2013-07-01

    Researchers have proposed that an explicit reasoning system is responsible for learning rule-based category structures and that a separate implicit, procedural-learning system is responsible for learning information-integration category structures. As evidence for this multiple-system hypothesis, researchers report a dissociation based on category-number manipulations in which rule-based category learning is worse when the category is composed of 4, rather than 2, response categories; however, information-integration category learning is unaffected by category-number manipulations. We argue that within the reported category-number manipulations, there exists a critical confound: Perceptual clusters used to construct the categories are spread apart in the 4-category condition relative to the 2-category one. The present research shows that when this confound is eliminated, performance on information-integration category learning is worse for 4 categories than for 2 categories, and this finding is demonstrated across 2 different information-integration category structures. Furthermore, model-based analyses indicate that a single-system learning model accounts well for both the original findings and the updated experimental findings reported here.

  17. Uncovering Contrast Categories in Categorization with a Probabilistic Threshold Model

    ERIC Educational Resources Information Center

    Verheyen, Steven; De Deyne, Simon; Dry, Matthew J.; Storms, Gert

    2011-01-01

    A contrast category effect on categorization occurs when the decision to apply a category term to an entity not only involves a comparison between the entity and the target category but is also influenced by a comparison of the entity with 1 or more alternative categories from the same domain as the target. Establishing a contrast category effect…

  18. A Probabilistic Account of Exemplar and Category Generation

    ERIC Educational Resources Information Center

    Jern, Alan; Kemp, Charles

    2013-01-01

    People are capable of imagining and generating new category exemplars and categories. This ability has not been addressed by previous models of categorization, most of which focus on classifying category exemplars rather than generating them. We develop a formal account of exemplar and category generation which proposes that category knowledge is…

  19. Uncovering Contrast Categories in Categorization with a Probabilistic Threshold Model

    ERIC Educational Resources Information Center

    Verheyen, Steven; De Deyne, Simon; Dry, Matthew J.; Storms, Gert

    2011-01-01

    A contrast category effect on categorization occurs when the decision to apply a category term to an entity not only involves a comparison between the entity and the target category but is also influenced by a comparison of the entity with 1 or more alternative categories from the same domain as the target. Establishing a contrast category effect…

  20. A Probabilistic Account of Exemplar and Category Generation

    ERIC Educational Resources Information Center

    Jern, Alan; Kemp, Charles

    2013-01-01

    People are capable of imagining and generating new category exemplars and categories. This ability has not been addressed by previous models of categorization, most of which focus on classifying category exemplars rather than generating them. We develop a formal account of exemplar and category generation which proposes that category knowledge is…

  1. Neuronal integration in visual cortex elevates face category tuning to conscious face perception.

    PubMed

    Fahrenfort, Johannes J; Snijders, Tineke M; Heinen, Klaartje; van Gaal, Simon; Scholte, H Steven; Lamme, Victor A F

    2012-12-26

    The human brain has the extraordinary capability to transform cluttered sensory input into distinct object representations. For example, it is able to rapidly and seemingly without effort detect object categories in complex natural scenes. Surprisingly, category tuning is not sufficient to achieve conscious recognition of objects. What neural process beyond category extraction might elevate neural representations to the level where objects are consciously perceived? Here we show that visible and invisible faces produce similar category-selective responses in the ventral visual cortex. The pattern of neural activity evoked by visible faces could be used to decode the presence of invisible faces and vice versa. However, only visible faces caused extensive response enhancements and changes in neural oscillatory synchronization, as well as increased functional connectivity between higher and lower visual areas. We conclude that conscious face perception is more tightly linked to neural processes of sustained information integration and binding than to processes accommodating face category tuning.

  2. Nutrient attenuation in rivers and streams, Puget Sound Basin, Washington

    USGS Publications Warehouse

    Sheibley, Rich W.; Konrad, Christopher P.; Black, Robert W.

    2015-01-01

    From a management perspective, preservation and improvement of instream nutrient attenuation should focus on increasing the travel time through a reach and contact time of water sediment (reactive) surfaces and lowering nutrient concentrations (and loads) to avoid saturation of instream attenuation and increase attenuation efficiency. These goals can be reached by maintaining and restoring channel-flood plain connectivity, maintaining and restoring healthy riparian zones along streams, managing point and nonpoint nutrient loads to streams and rivers, and restoring channel features that promote attenuation such as the addition of woody debris and maintaining pool-riffle morphologies. Many of these management approaches are already being undertaken during projects aimed to restore quality salmon habitat. Therefore, there is a dual benefit to these projects that also may lead to enhanced potential for nitrogen and phosphorus attenuation.

  3. Event-related potential parameters of category and property violations during semantic category-based induction.

    PubMed

    Long, Changquan; Lei, Xu; Chen, Jie; Chang, Yun; Chen, Antao; Li, Hong

    2015-06-01

    Previous studies have failed to clarify the event-related potentials (ERPs) that occur in response to categorization and property inferences during category-based induction. The present study examined ERP differences among acceptable-induction conclusions, unrelated-category conclusions, and unrelated-property conclusions to dissociate categorization and property-inference processing during category-based induction. The results showed that: (a) conclusions with categories that were unrelated to the premise evoked greater frontal N2 amplitudes, smaller P3b amplitudes, and greater N400 amplitudes, compared to conclusions with categories that were logically related to the premise; and (b) conclusions with unrelated properties evoked larger late positive components (LPCs) during the 700-800ms time interval compared to conclusions with related properties. These results suggest that the N2-P3b-N400 effects reflect categorization violations, while the LPCs are related to property violations during category-based induction, therefore, the ERP responses to category-related and property-related processes are dissociated respectively during category-based induction. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Typicality Mediates Performance during Category Verification in Both Ad-Hoc and Well-Defined Categories

    ERIC Educational Resources Information Center

    Sandberg, Chaleece; Sebastian, Rajani; Kiran, Swathi

    2012-01-01

    Background: The typicality effect is present in neurologically intact populations for natural, ad-hoc, and well-defined categories. Although sparse, there is evidence of typicality effects in persons with chronic stroke aphasia for natural and ad-hoc categories. However, it is unknown exactly what influences the typicality effect in this…

  5. Category Label Effects on Chinese Children's Inductive Inferences: Modulation by Perceptual Detail and Category Specificity

    ERIC Educational Resources Information Center

    Long, Changquan; Lu, Xiaoying; Zhang, Li; Li, Hong; Deak, Gedeon O.

    2012-01-01

    Inductive generalization of novel properties to same-category or similar-looking objects was studied in Chinese preschool children. The effects of category labels on generalizations were investigated by comparing basic-level labels, superordinate-level labels, and a control phrase applied to three kinds of stimulus materials: colored photographs…

  6. Category Label Effects on Chinese Children's Inductive Inferences: Modulation by Perceptual Detail and Category Specificity

    ERIC Educational Resources Information Center

    Long, Changquan; Lu, Xiaoying; Zhang, Li; Li, Hong; Deak, Gedeon O.

    2012-01-01

    Inductive generalization of novel properties to same-category or similar-looking objects was studied in Chinese preschool children. The effects of category labels on generalizations were investigated by comparing basic-level labels, superordinate-level labels, and a control phrase applied to three kinds of stimulus materials: colored photographs…

  7. Typicality Mediates Performance during Category Verification in Both Ad-Hoc and Well-Defined Categories

    ERIC Educational Resources Information Center

    Sandberg, Chaleece; Sebastian, Rajani; Kiran, Swathi

    2012-01-01

    Background: The typicality effect is present in neurologically intact populations for natural, ad-hoc, and well-defined categories. Although sparse, there is evidence of typicality effects in persons with chronic stroke aphasia for natural and ad-hoc categories. However, it is unknown exactly what influences the typicality effect in this…

  8. 40 CFR 94.106 - Supplemental test procedures for Category 1 and Category 2 marine engines.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... heated by the engine); (ii) Without correction at any ambient water temperature (or equivalent) between 5... commercial Category 1 engines certified using the duty cycle specified in § 94.105(b), the Not to Exceed... Exceed zone which follows: ER29DE99.002 (2) For Category 2 engines certified using the duty...

  9. Development of Implicit and Explicit Category Learning

    ERIC Educational Resources Information Center

    Huang-Pollock, Cynthia L.; Maddox, W. Todd; Karalunas, Sarah L.

    2011-01-01

    We present two studies that examined developmental differences in the implicit and explicit acquisition of category knowledge. College-attending adults consistently outperformed school-age children on two separate information-integration paradigms due to children's more frequent use of an explicit rule-based strategy. Accuracy rates were also…

  10. 32 CFR 901.10 - Presidential category.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SCHOOLS APPOINTMENT TO THE UNITED STATES AIR FORCE ACADEMY Nomination Procedures and Requirements § 901.10... the year that the candidate would enter the U.S. Air Force Academy; or (2) The parent was retired with... the Presidential category.) (b) An eligible individual applies to USAFA/RRS, U.S. Air Force Academy...

  11. 32 CFR 901.16 - Superintendent category.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SCHOOLS APPOINTMENT TO THE UNITED STATES AIR FORCE ACADEMY Nomination Procedures and Requirements § 901.16 Superintendent category. Fifty eligible applicants who have not secured a nomination to the Academy from any... selected for nomination from the nationwide precandidate program by the Academy. Appointments from this...

  12. Multimedia Category Preferences of Working Engineers

    ERIC Educational Resources Information Center

    Baukal, Charles E., Jr.; Ausburn, Lynna J.

    2016-01-01

    Many have argued for the importance of continuing engineering education (CEE), but relatively few recommendations were found in the literature for how to use multimedia technologies to deliver it most effectively. The study reported here addressed this gap by investigating the multimedia category preferences of working engineers. Four categories…

  13. The Schetic Categories of the Tlingit Verb.

    ERIC Educational Resources Information Center

    Leer, Jeffry A.

    An analysis of verbs in Tlingit, a U.S. Northwest Coast Indian language, begins with an overview of its situation and usage and of previous research. The second chapter sketches its phonological and syntactic characteristics. Subsequent chapters deal specifically with the verb. An analysis of verb categories distinguishes two groups: argumental…

  14. Opposite RHOA functions within the ATLL category.

    PubMed

    Ishikawa, Shumpei

    2016-02-04

    In this issue of Blood, Nagata et al reported that different Ras homolog gene family, member A (RHOA) hotspot mutations among the adult T-cell leukemia/lymphoma (ATLL) category have opposite biochemical activities, which are linked to different T-cell phenotypes.

  15. Learning Phonetic Categories by Tracking Movements

    ERIC Educational Resources Information Center

    Gauthier, Bruno; Shi, Rushen; Xu, Yi

    2007-01-01

    We explore in this study how infants may derive phonetic categories from adult input that are highly variable. Neural networks in the form of self-organizing maps (SOMs; Kohonen, 1989, 1995) were used to simulate unsupervised learning of Mandarin tones. In Simulation 1, we trained the SOMs with syllable-sized continuous F[subscript 0] contours,…

  16. Young Children's Automatic Encoding of Social Categories

    ERIC Educational Resources Information Center

    Weisman, Kara; Johnson, Marissa V.; Shutts, Kristin

    2015-01-01

    The present research investigated young children's automatic encoding of two social categories that are highly relevant to adults: gender and race. Three- to 6-year-old participants learned facts about unfamiliar target children who varied in either gender or race and were asked to remember which facts went with which targets. When participants…

  17. Learning Phonetic Categories by Tracking Movements

    ERIC Educational Resources Information Center

    Gauthier, Bruno; Shi, Rushen; Xu, Yi

    2007-01-01

    We explore in this study how infants may derive phonetic categories from adult input that are highly variable. Neural networks in the form of self-organizing maps (SOMs; Kohonen, 1989, 1995) were used to simulate unsupervised learning of Mandarin tones. In Simulation 1, we trained the SOMs with syllable-sized continuous F[subscript 0] contours,…

  18. Listeners Retune Phoneme Categories across Languages

    ERIC Educational Resources Information Center

    Reinisch, Eva; Weber, Andrea; Mitterer, Holger

    2013-01-01

    Native listeners adapt to noncanonically produced speech by retuning phoneme boundaries by means of lexical knowledge. We asked whether a second language lexicon can also guide category retuning and whether perceptual learning transfers from a second language (L2) to the native language (L1). During a Dutch lexical-decision task, German and Dutch…

  19. Categories Influence Predictions about Individual Consistency

    ERIC Educational Resources Information Center

    Rhodes, Marjorie; Gelman, Susan A.

    2008-01-01

    Predicting how people will behave in the future is a critical social-cognitive task. In four studies (N = 150, ages preschool to adult), young children (ages 4-5) used category information to guide their expectations about individual consistency. They predicted that psychological properties (preferences and fears) would remain consistent over time…

  20. Right-of-Way Category Manual.

    ERIC Educational Resources Information Center

    Bowman, James S.; Turmel, Jon P.

    This manual provides information needed to meet the standards for pesticide applicator certification. The thrust of this document is vegetation management in public service rights-of-way such as along utility lines, railroads and highways. Different categories of herbicides are discussed with attention given to how they should be applied, the…