Functional modeling of the human auditory brainstem response to broadband stimulationa)

PubMed Central

Verhulst, Sarah; Bharadwaj, Hari M.; Mehraei, Golbarg; Shera, Christopher A.; Shinn-Cunningham, Barbara G.

2015-01-01

Population responses such as the auditory brainstem response (ABR) are commonly used for hearing screening, but the relationship between single-unit physiology and scalp-recorded population responses are not well understood. Computational models that integrate physiologically realistic models of single-unit auditory-nerve (AN), cochlear nucleus (CN) and inferior colliculus (IC) cells with models of broadband peripheral excitation can be used to simulate ABRs and thereby link detailed knowledge of animal physiology to human applications. Existing functional ABR models fail to capture the empirically observed 1.2–2 ms ABR wave-V latency-vs-intensity decrease that is thought to arise from level-dependent changes in cochlear excitation and firing synchrony across different tonotopic sections. This paper proposes an approach where level-dependent cochlear excitation patterns, which reflect human cochlear filter tuning parameters, drive AN fibers to yield realistic level-dependent properties of the ABR wave-V. The number of free model parameters is minimal, producing a model in which various sources of hearing-impairment can easily be simulated on an individualized and frequency-dependent basis. The model fits latency-vs-intensity functions observed in human ABRs and otoacoustic emissions while maintaining rate-level and threshold characteristics of single-unit AN fibers. The simulations help to reveal which tonotopic regions dominate ABR waveform peaks at different stimulus intensities. PMID:26428802

Are there Race-Dependent Endothelial Cell Responses to Exercise?

PubMed Central

Brown, Michael D.; Feairheller, Deborah L.

2013-01-01

African Americans have endothelial dysfunction which likely contributes to their high prevalence of hypertension. Endothelial cell responses to stimuli could play a role in the development of endothelial dysfunction and hypertension. High physiological levels of vascular laminar shear stress can profoundly alter endothelial cell phenotype. It is not known whether there are race-dependent endothelial cell responses to laminar shear stress. PMID:23262464

An item response theory analysis of nicotine dependence symptoms in recent onset adolescent smokers.

PubMed

Rose, Jennifer S; Dierker, Lisa C

2010-07-01

Given absence of a "gold standard" for measuring self-reported nicotine dependence, particularly among less experienced smokers, there is a need to evaluate existing measures to determine how well symptoms measure the underlying nicotine dependence construct and whether symptoms function differently for less experienced smokers. Study aims were to determine (1) likelihood of endorsement of individual symptoms at different levels of a nicotine dependence construct and the ability of symptoms to discriminate between different levels of this construct and (2) whether these symptom properties varied between nondaily and daily smokers. We used multiple group item response theory analysis to evaluate nicotine dependence symptoms from the nicotine dependence syndrome scale based on a nationally representative sample of 8081 recent onset adolescent smokers from the national surveys on drug use and health. After controlling for age, gender, smoking quantity and length of smoking exposure, symptoms assessing tolerance were invariant across nondaily and daily smokers, and discriminated well between levels of the nicotine dependence construct. However, the majority of symptoms functioned differently for nondaily and daily smokers. These symptoms did not discriminate as well between levels of the nicotine dependence construct and were more likely to be endorsed at lower levels of this construct for daily smokers. A measure that encompasses a range of symptoms tapping different aspects of smoking may be ideally suited for nondaily adolescent smokers, while an ideal measure of nicotine dependence for daily smokers might also include more core diagnostic features of nicotine dependence such as withdrawal and tolerance. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Thought Suppression, Impaired Regulation of Urges, and Addiction-Stroop Predict Affect-Modulated Cue-Reactivity among Alcohol Dependent Adults

PubMed Central

Garland, Eric L.; Carter, Kristin; Ropes, Katie; Howard, Matthew O.

2011-01-01

Abstinent alcohol dependent individuals commonly employ thought suppression to cope with stress and intrusive cognitions about alcohol. This strategy may inadvertently bias attention toward alcohol-related stimuli while depleting neurocognitive resources needed to regulate urges, manifested as decreased heart rate variability (HRV) responsivity to alcohol cues. The present study tested the hypothesis that trait and state thought suppression, impaired regulation of urges, and alcohol attentional bias as measured by the Addiction-Stroop would have significant effects on the HRV responsivity of 58 adults in residential treatment for alcohol dependence (mean age = 39.6 ± 9.4, 81% female) who participated in an affect-modulated cue-reactivity protocol. Regression analyses controlling for age, level of pre-treatment alcohol consumption, and baseline HRV indicated that higher levels of trait thought suppression, impaired regulation of alcohol urges, and attentional fixation on alcohol cues were associated with lower HRV responsivity during stress-primed alcohol cue-exposure. Moreover, there was a significant state X trait suppression interaction on HRV cue-responsivity, such that alcohol dependent persons reporting high levels of state and trait suppression exhibited less HRV during cue-exposure than persons reporting low levels of state and trait suppression. Results suggest that chronic thought suppression taxes regulatory resources reflected in reduced HRV responsivity, an effect that is particularly evident when high trait suppressors engage in intensive suppression of drinking-related thoughts under conditions of stress. Treatment approaches that offer effective alternatives to the maladaptive strategy of suppressing alcohol urges may be crucial for relapse prevention. PMID:21967855

Thought suppression, impaired regulation of urges, and Addiction-Stroop predict affect-modulated cue-reactivity among alcohol dependent adults.

PubMed

Garland, Eric L; Carter, Kristin; Ropes, Katie; Howard, Matthew O

2012-01-01

Abstinent alcohol dependent individuals commonly employ thought suppression to cope with stress and intrusive cognitions about alcohol. This strategy may inadvertently bias attention towards alcohol-related stimuli while depleting neurocognitive resources needed to regulate urges, manifested as decreased heart rate variability (HRV) responsivity to alcohol cues. The present study tested the hypothesis that trait and state thought suppression, impaired regulation of urges, and alcohol attentional bias as measured by the Addiction-Stroop would have significant effects on the HRV responsivity of 58 adults in residential treatment for alcohol dependence (mean age=39.6 ± 9.4, 81% female) who participated in an affect-modulated cue-reactivity protocol. Regression analyses controlling for age, level of pre-treatment alcohol consumption, and baseline HRV indicated that higher levels of trait thought suppression, impaired regulation of alcohol urges, and attentional fixation on alcohol cues were associated with lower HRV responsivity during stress-primed alcohol cue-exposure. Moreover, there was a significant state × trait suppression interaction on HRV cue-responsivity, such that alcohol dependent persons reporting high levels of state and trait suppression exhibited less HRV during cue-exposure than persons reporting low levels of state and trait suppression. Results suggest that chronic thought suppression taxes regulatory resources reflected in reduced HRV responsivity, an effect that is particularly evident when high trait suppressors engage in intensive suppression of drinking-related thoughts under conditions of stress. Treatment approaches that offer effective alternatives to the maladaptive strategy of suppressing alcohol urges may be crucial for relapse prevention. Copyright © 2011 Elsevier B.V. All rights reserved.

An Item Response Theory Modeling of Alcohol and Marijuana Dependences: A National Drug Abuse Treatment Clinical Trials Network Study*

PubMed Central

Wu, Li-Tzy; Pan, Jeng-Jong; Blazer, Dan G.; Tai, Betty; Stitzer, Maxine L.; Brooner, Robert K.; Woody, George E.; Patkar, Ashwin A.; Blaine, Jack D.

2009-01-01

Objective: The aim of this study was to examine psychometric properties of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), diagnostics criteria for alcohol and marijuana dependences among 462 alcohol users and 311 marijuana users enrolled in two multisite trials of the National Drug Abuse Treatment Clinical Trials Network. Method: Diagnostic questions were assessed by the DSM-IV checklist. Data were analyzed by the item response theory and the multiple indicators–multiple causes method procedures. Results: Criterion symptoms of alcohol and marijuana dependences exhibited a high level of internal consistency. All individual symptoms showed good discrimination in distinguishing alcohol or marijuana users between high and low severity levels of the continuum. In both groups, “withdrawal” appeared to measure the most severe symptom of the dependence continuum. There was little evidence of measurement nonequivalence in assessing symptoms of dependence by gender, age, race/ethnicity, and educational level. Conclusions: These findings highlight the clinical utility of the DSM-IV checklist in assessing alcohol- and marijuana-dependence syndromes among treatment-seeking substance users. PMID:19371493

RMP Guidance for Chemical Distributors - Chapter 8: Emergency Response Program

EPA Pesticide Factsheets

Depending on the level of processes at your facility, part 68 may require an emergency response program: an emergency response plan, emergency response equipment procedures, employee training, and procedures to ensure the program is up-to-date.

Reinforcement and substitution in humans: a multiple-response analysis1

PubMed Central

Bernstein, Daniel J.; Ebbesen, Ebbe B.

1978-01-01

Three adult human subjects engaged in activities such as reading, sewing, artwork, and candlemaking while living alone in a laboratory apartment 24 hours per day for several weeks. After a baseline period in which the activities were fully available, access to a particular activity (contingent response) was made dependent on engaging in another less-preferred activity (instrumental response). The contingencies produced substantial increases in instrumental responding, and responding decreased toward baseline levels when the dependency was removed. Under the contingent conditions, time earned for the concurrent activity was always less than the baseline level. To determine the contribution of this reduction to the instrumental increase, access to the contingent activity was restricted in the absence of any dependency. The results indicated that increases among responses that filled the newly available time could be selective, e.g., artwork increased when reading was restricted but candlemaking did not. It was concluded that the reductions in the contingent response that accompany contingencies usually do not exclusively determine instrumental increases, but selective increases can contribute to the increase in time devoted to the instrumental response. PMID:16812105

The toxic effects of ammonia exposure on antioxidant and immune responses in Rockfish, Sebastes schlegelii during thermal stress.

PubMed

Kim, Shin-Hu; Kim, Jun-Hwan; Park, Myoung-Ae; Hwang, Seong Don; Kang, Ju-Chan

2015-11-01

Rockfish, Sebastes schlegelii (mean weight 14.53 ± 1.14 cm, and mean weight 38.36 ± 3.45 g) were exposed for 4 weeks (2 weeks and 4 weeks) with the different levels of ammonia in the concentrations of 0, 0.1, 0.5, 1.0mg/L at 19 and 24°C. The ammonia exposure induced significant alterations in antioxidant responses. The activities of SOD, CAT, and GST were considerably increased by the ammonia exposure depending on water temperature, whereas the GSH level was notably decreased after 2 and 4 weeks. In the stress indicators, the cortisol and HSP 70 were significantly elevated by the exposure to ammonia depending on water temperature. In innate immune responses, the phagocytosis and lysozyme activity were notably decreased by ammonia exposure depending on water temperature after 2 and 4 weeks. The results suggest that ammonia exposure depending on water temperature can induce the considerable alterations in antioxidant responses, stress, and immune inhibition. Copyright © 2015 Elsevier B.V. All rights reserved.

Dependency, self-criticism and negative affective responses following imaginary rejection and failure threats: meaning-making processes as moderators or mediators.

PubMed

Besser, Avi; Priel, Beatriz

2011-01-01

This study evaluated the intervening role of meaning-making processes in emotional responses to negative life events based on Blatt's (1974, 2004) formulations concerning the role of personality predispositions in depression. In a pre/post within-subject study design, a community sample of 233 participants reacted to imaginary scenarios of interpersonal rejection and achievement failure. Meaning-making processes relating to threats to self-definition and interpersonal relatedness were examined following the exposure to the scenarios. The results indicated that the personality predisposition of Dependency, but not Self-Criticism predicted higher levels of negative affect following the interpersonal rejection event, independent of baseline levels of negative affect. This effect was mediated by higher levels of negative meaning-making processes related to the effect of the interpersonal rejection scenario on Dependent individuals' senses of interpersonal relatedness and self-worth. In addition, both Self-Criticism and Dependency predicted higher levels of negative affect following the achievement failure event, independent of baseline levels of negative affect. Finally, the effect of Self-Criticism was mediated by higher levels of negative meaning-making processes related to the effect of the achievement failure scenario on self-critical individuals' senses of self-definition.

Sea Level Rise National Coastal Property Model

EPA Science Inventory

The impact of sea level rise on coastal properties depends critically on the human response to the threat, which in turn depends on several factors, including the immediacy of the risk, the magnitude of property value at risk, options for adapting to the threat and the cost of th...

A Pole-Zero Filter Cascade Provides Good Fits to Human Masking Data and to Basilar Membrane and Neural Data

NASA Astrophysics Data System (ADS)

Lyon, Richard F.

2011-11-01

A cascade of two-pole-two-zero filters with level-dependent pole and zero dampings, with few parameters, can provide a good match to human psychophysical and physiological data. The model has been fitted to data on detection threshold for tones in notched-noise masking, including bandwidth and filter shape changes over a wide range of levels, and has been shown to provide better fits with fewer parameters compared to other auditory filter models such as gammachirps. Originally motivated as an efficient machine implementation of auditory filtering related to the WKB analysis method of cochlear wave propagation, such filter cascades also provide good fits to mechanical basilar membrane data, and to auditory nerve data, including linear low-frequency tail response, level-dependent peak gain, sharp tuning curves, nonlinear compression curves, level-independent zero-crossing times in the impulse response, realistic instantaneous frequency glides, and appropriate level-dependent group delay even with minimum-phase response. As part of exploring different level-dependent parameterizations of such filter cascades, we have identified a simple sufficient condition for stable zero-crossing times, based on the shifting property of the Laplace transform: simply move all the s-domain poles and zeros by equal amounts in the real-s direction. Such pole-zero filter cascades are efficient front ends for machine hearing applications, such as music information retrieval, content identification, speech recognition, and sound indexing.

Upregulation of capacity for glutathione synthesis in response to amino acid deprivation: regulation of glutamate-cysteine ligase subunits

PubMed Central

Sikalidis, Angelos K.; Mazor, Kevin M.; Lee, Jeong-In; Roman, Heather B.; Hirschberger, Lawrence L.; Stipanuk, Martha H.

2014-01-01

Using HepG2/C3A cells and MEFs, we investigated whether induction of GSH synthesis in response to sulfur amino acid deficiency is mediated by the decrease in cysteine levels or whether it requires a decrease in GSH levels per se. Both the glutamate-cysteine ligase catalytic (GCLC) and modifier (GCLM) subunit mRNA levels were upregulated in response to a lack of cysteine or other essential amino acids, independent of GSH levels. This upregulation did not occur in MEFs lacking GCN2 (general control non-derepressible 2, also known as eIF2α kinase 4) or in cells expressing mutant eIF2α lacking the eIF2α kinase Ser51 phosphorylation site, indicating that expression of both GCLC and GCLM was mediated by the GCN2/ATF4 stress response pathway. Only the increase in GCLM mRNA level, however, was accompanied by a parallel increase in protein expression, suggesting that the enhanced capacity for GSH synthesis depended largely on increased association of GCLC with its regulatory subunit. Upregulation of both GCLC and GLCM mRNA levels in response to cysteine deprivation was dependent on new protein synthesis, which is consistent with expression of GCLC and GCLM being mediated by proteins whose synthesis depends on activation of the GCN2/ATF4 pathway. Our data suggest that the regulation of GCLC expression may be mediated by changes in the abundance of transcriptional regulators, whereas the regulation of GCLM expression may be mediated by changes in the abundance of mRNA stabilizing or destabilizing proteins. Upregulation of GCLM levels in response to low cysteine levels may serve to protect the cell in the face of a future stress requiring GSH as an antioxidant or conjugating/detoxifying agent. PMID:24557597

Dose-dependent effects of an immune challenge at both ultimate and proximate levels in Drosophila melanogaster.

PubMed

Nystrand, M; Dowling, D K

2014-05-01

Immune responses are highly dynamic. The magnitude and efficiency of an immune response to a pathogen can change markedly across individuals, and such changes may be influenced by variance in a range of intrinsic (e.g. age, genotype, sex) and external (e.g. abiotic stress, pathogen identity, strain) factors. Life history theory predicts that up-regulation of the immune system will come at a physiological cost, and studies have confirmed that increased investment in immunity can reduce reproductive output and survival. Furthermore, males and females often have divergent reproductive strategies, and this might drive the evolution of sex-specific life history trade-offs involving immunity, and sexual dimorphism in immune responses per se. Here, we employ an experiment design to elucidate dose-dependent and sex-specific responses to exposure to a nonpathogenic immune elicitor at two scales--the 'ultimate' life history and the underlying 'proximate' immune level in Drosophila melanogaster. We found dose-dependent effects of immune challenges on both male and female components of reproductive success, but not on survival, as well as a response in antimicrobial activity. These results indicate that even in the absence of the direct pathogenic effects that are associated with actual disease, individual life histories respond to a perceived immune challenge--but with the magnitude of this response being contingent on the initial dose of exposure. Furthermore, the results indicate that immune responses at the ultimate life history level may indeed reflect underlying processes that occur at the proximate level. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

The Calcium-Dependent Protein Kinase CPK28 Regulates Development by Inducing Growth Phase-Specific, Spatially Restricted Alterations in Jasmonic Acid Levels Independent of Defense Responses in Arabidopsis[OPEN

PubMed Central

Matschi, Susanne; Hake, Katharina; Herde, Marco; Hause, Bettina; Romeis, Tina

2015-01-01

Phytohormones play an important role in development and stress adaptations in plants, and several interacting hormonal pathways have been suggested to accomplish fine-tuning of stress responses at the expense of growth. This work describes the role played by the CALCIUM-DEPENDENT PROTEIN KINASE CPK28 in balancing phytohormone-mediated development in Arabidopsis thaliana, specifically during generative growth. cpk28 mutants exhibit growth reduction solely as adult plants, coinciding with altered balance of the phytohormones jasmonic acid (JA) and gibberellic acid (GA). JA-dependent gene expression and the levels of several JA metabolites were elevated in a growth phase-dependent manner in cpk28, and accumulation of JA metabolites was confined locally to the central rosette tissue. No elevated resistance toward herbivores or necrotrophic pathogens was detected for cpk28 plants, either on the whole-plant level or specifically within the tissue displaying elevated JA levels. Abolishment of JA biosynthesis or JA signaling led to a full reversion of the cpk28 growth phenotype, while modification of GA signaling did not. Our data identify CPK28 as a growth phase-dependent key negative regulator of distinct processes: While in seedlings, CPK28 regulates reactive oxygen species-mediated defense signaling; in adult plants, CPK28 confers developmental processes by the tissue-specific balance of JA and GA without affecting JA-mediated defense responses. PMID:25736059

A review of calibrated blood oxygenation level-dependent (BOLD) methods for the measurement of task-induced changes in brain oxygen metabolism

PubMed Central

Blockley, Nicholas P.; Griffeth, Valerie E. M.; Simon, Aaron B.; Buxton, Richard B.

2013-01-01

The dynamics of the blood oxygenation level-dependent (BOLD) response are dependent on changes in cerebral blood flow, cerebral blood volume and the cerebral metabolic rate of oxygen consumption. Furthermore, the amplitude of the response is dependent on the baseline physiological state, defined by the haematocrit, oxygen extraction fraction and cerebral blood volume. As a result of this complex dependence, the accurate interpretation of BOLD data and robust intersubject comparisons when the baseline physiology is varied are difficult. The calibrated BOLD technique was developed to address these issues. However, the methodology is complex and its full promise has not yet been realised. In this review, the theoretical underpinnings of calibrated BOLD, and issues regarding this theory that are still to be resolved, are discussed. Important aspects of practical implementation are reviewed and reported applications of this methodology are presented. PMID:22945365

Item Response Theory Analysis of DSM-IV Cannabis Abuse and Dependence Criteria in Adolescents

ERIC Educational Resources Information Center

Hartman, Christie A.; Gelhorn, Heather; Crowley, Thomas J.; Sakai, Joseph T.; Stallings, Michael; Young, Susan E.; Rhee, Soo Hyun; Corley, Robin; Hewitt, John K.; Hopfer, Christian J.

2008-01-01

A study to examine the DSM-IV criteria for cannabis abuse and dependence among adolescents is conducted. Results conclude that abuse and dependence criteria were not found to affect the different levels of severity in cannabis use.

Response of iron overload to deferasirox in rare transfusion-dependent anaemias: equivalent effects on serum ferritin and labile plasma iron for haemolytic or production anaemias

PubMed Central

Porter, John B; Lin, Kai-Hsin; Beris, Photis; Forni, Gian Luca; Taher, Ali; Habr, Dany; Domokos, Gabor; Roubert, Bernard; Thein, Swee Lay

2011-01-01

Objectives It is widely assumed that, at matched transfusional iron-loading rates, responses to chelation therapy are similar, irrespective of the underlying condition. However, data are limited for rare transfusion-dependent anaemias, and it remains to be elucidated if response differs, depending on whether the anaemia has a primary haemolytic or production mechanism. Methods The efficacy and safety of deferasirox (Exjade®) in rare transfusion-dependent anaemias were evaluated over 1 yr, with change in serum ferritin as the primary efficacy endpoint. Initial deferasirox doses were 10–30 mg/kg/d, depending on transfusion requirements; 34 patients had production anaemias, and 23 had haemolytic anaemias. Results Patients with production anaemias or haemolytic anaemias had comparable transfusional iron-loading rates (0.31 vs. 0.30 mL red blood cells/kg/d), mean deferasirox dosing (19.3 vs. 19.0 mg/kg/d) and baseline median serum ferritin (2926 vs. 2682 ng/mL). Baseline labile plasma iron (LPI) levels correlated significantly with the transfusional iron-loading rates and with serum ferritin levels in both cohorts. Reductions in median serum ferritin levels were initially faster in the production than the haemolytic anaemias, but at 1 yr, similar significant reductions of 940 and 617 ng/mL were attained, respectively (−26.0% overall). Mean LPI decreased significantly in patients with production (P < 0.0001) and haemolytic (P = 0.037) anaemias after the first dose and was maintained at normal mean levels (<0.4 μm) subsequently. The most common drug-related, investigator-assessed adverse events were diarrhoea (n = 16) and nausea (n = 12). Conclusions At matched transfusional iron-loading rates, the responses of rare transfusion-dependent anaemias to deferasirox are similar at 1 yr, irrespective of the underlying pathogenic mechanism. PMID:21649735

Response of iron overload to deferasirox in rare transfusion-dependent anaemias: equivalent effects on serum ferritin and labile plasma iron for haemolytic or production anaemias.

PubMed

Porter, John B; Lin, Kai-Hsin; Beris, Photis; Forni, Gian Luca; Taher, Ali; Habr, Dany; Domokos, Gabor; Roubert, Bernard; Thein, Swee Lay

2011-10-01

It is widely assumed that, at matched transfusional iron-loading rates, responses to chelation therapy are similar, irrespective of the underlying condition. However, data are limited for rare transfusion-dependent anaemias, and it remains to be elucidated if response differs, depending on whether the anaemia has a primary haemolytic or production mechanism. The efficacy and safety of deferasirox (Exjade®) in rare transfusion-dependent anaemias were evaluated over 1 yr, with change in serum ferritin as the primary efficacy endpoint. Initial deferasirox doses were 10-30 mg/kg/d, depending on transfusion requirements; 34 patients had production anaemias, and 23 had haemolytic anaemias. Patients with production anaemias or haemolytic anaemias had comparable transfusional iron-loading rates (0.31 vs. 0.30 mL red blood cells/kg/d), mean deferasirox dosing (19.3 vs. 19.0 mg/kg/d) and baseline median serum ferritin (2926 vs. 2682 ng/mL). Baseline labile plasma iron (LPI) levels correlated significantly with the transfusional iron-loading rates and with serum ferritin levels in both cohorts. Reductions in median serum ferritin levels were initially faster in the production than the haemolytic anaemias, but at 1 yr, similar significant reductions of 940 and 617 ng/mL were attained, respectively (-26.0% overall). Mean LPI decreased significantly in patients with production (P < 0.0001) and haemolytic (P = 0.037) anaemias after the first dose and was maintained at normal mean levels (< 0.4 μm) subsequently. The most common drug-related, investigator-assessed adverse events were diarrhoea (n = 16) and nausea (n = 12). At matched transfusional iron-loading rates, the responses of rare transfusion-dependent anaemias to deferasirox are similar at 1 yr, irrespective of the underlying pathogenic mechanism. © 2011 John Wiley & Sons A/S.

Influence of NaCl on Growth, Proline, and Phosphoenolpyruvate Carboxylase Levels in Mesembryanthemum crystallinum Suspension Cultures 1

PubMed Central

Thomas, John C.; De Armond, Richard L.; Bohnert, Hans J.

1992-01-01

The facultative halophyte Mesembryanthemum crystallinum responds to salt stress by increasing the levels of phosphoenolpyruvate carboxylase (PEPCase) and other enzymes associated with Crassulacean acid metabolism. A more common response to salt stress in sensitive and tolerant species, including M. crystallinum, is the accumulation of proline. We have established M. crystallinum suspension cultures to investigate whether both these salt-induced responses occur at the cellular level. Leaf-and root-derived cultures maintain 5% of the total soluble amino acids as proline. Cell culture growth slows upon addition of 400 millimolar NaCl, and proline levels increase to 40% of the total soluble amino acids. These results suggest a functional salt-stress and response program in Mesembryanthemum cells. Suspension cultures grown with or without 400 millimolar NaCl have PEPCase levels that compare with those from roots and unstressed leaves. The predominant protein cross-reacting with an anti-PEPCase antibody corresponds to 105 kilodaltons (apparent molecular mass), whereas a second species of approximately 110 kilodaltons is present at low levels. In salt-stressed leaves, the 110 kilodalton protein is more prevalent. Levels of mRNA for both ppc1 (salt stress induced in leaves) and ppc2 (constitutive) genes in salt-treated suspensions cultures are equal to unstressed leaves, and only twice the levels found in untreated suspension cultures. Whereas cells accumulate proline in response to NaCl, PEPCase protein amounts remain similar in salt-treated and untreated cultures. The induction upon salt stress of the 110 kilodalton PEPCase protein and other Crassulacean acid metabolism enzymes in organized tissues is not observed in cell culture and may depend on tissue-dependent or photoautotrophy-dependent programs. ImagesFigure 4Figure 5 PMID:16668687

Nonparametric Regression and the Parametric Bootstrap for Local Dependence Assessment.

ERIC Educational Resources Information Center

Habing, Brian

2001-01-01

Discusses ideas underlying nonparametric regression and the parametric bootstrap with an overview of their application to item response theory and the assessment of local dependence. Illustrates the use of the method in assessing local dependence that varies with examinee trait levels. (SLD)

Characterization of Changes in Gene Expression and Biochemical Pathways at Low Levels of Benzene Exposure

PubMed Central

Thomas, Reuben; Hubbard, Alan E.; McHale, Cliona M.; Zhang, Luoping; Rappaport, Stephen M.; Lan, Qing; Rothman, Nathaniel; Vermeulen, Roel; Guyton, Kathryn Z.; Jinot, Jennifer; Sonawane, Babasaheb R.; Smith, Martyn T.

2014-01-01

Benzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML). Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC), we reported dose-dependent effects of benzene exposure on gene expression and biochemical pathways in 83 workers exposed across four airborne concentration ranges (from <1 ppm to >10 ppm) compared with 42 subjects with non-workplace ambient exposure levels. Here, we further characterize these dose-dependent effects with continuous benzene exposure in all 125 study subjects. We estimated air benzene exposure levels in the 42 environmentally-exposed subjects from their unmetabolized urinary benzene levels. We used a novel non-parametric, data-adaptive model selection method to estimate the change with dose in the expression of each gene. We describe non-parametric approaches to model pathway responses and used these to estimate the dose responses of the AML pathway and 4 other pathways of interest. The response patterns of majority of genes as captured by mean estimates of the first and second principal components of the dose-response for the five pathways and the profiles of 6 AML pathway response-representative genes (identified by clustering) exhibited similar apparent supra-linear responses. Responses at or below 0.1 ppm benzene were observed for altered expression of AML pathway genes and CYP2E1. Together, these data show that benzene alters disease-relevant pathways and genes in a dose-dependent manner, with effects apparent at doses as low as 100 ppb in air. Studies with extensive exposure assessment of subjects exposed in the low-dose range between 10 ppb and 1 ppm are needed to confirm these findings. PMID:24786086

40 CFR 63.490 - Batch front-end process vents-performance test methods and procedures to determine compliance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... limitation is not dependent upon any past production or activity level. (1) If the expected mix of products... acceptable if the response from the high-level calibration gas is at least 20 times the standard deviation of..., appendix A is acceptable if the response from the high-level calibration gas is at least 20 times the...

Interactive effects of nitrogen addition, warming and invasion across organizational levels in an old-field plant community.

PubMed

Gornish, Elise S

2014-10-08

Response to global change is dependent on the level of biological organization (e.g. the ecologically relevant spatial scale) in which species are embedded. For example, individual responses can affect population-level responses, which, in turn, can affect community-level responses. Although relationships are known to exist among responses to global change across levels of biological organization, formal investigations of these relationships are still uncommon. I conducted an exploratory analysis to identify how nitrogen addition and warming by open top chambers might affect plants across spatial scales by estimating treatment effect size at the leaf level, the plant level and the community level. Moreover, I investigated if the presence of Pityopsis aspera, an experimentally introduced plant species, modified the relationship between spatial scale and effect size across treatments. I found that, overall, the spatial scale significantly contributes to differences in effect size, supporting previous work which suggests that mechanisms driving biotic response to global change are scale dependent. Interestingly, the relationship between spatial scale and effect size in both the absence and presence of experimental invasion is very similar for nitrogen addition and warming treatments. The presence of invasion, however, did not affect the relationship between spatial scale and effect size, suggesting that in this system, invasion may not exacerbate or attenuate climate change effects. This exercise highlights the value of moving beyond integration and scaling to the practice of directly testing for scale effects within single experiments. Published by Oxford University Press on behalf of the Annals of Botany Company.

Low-level laser effects on bacterial cultures submitted to heat stress

NASA Astrophysics Data System (ADS)

Gonçalves, E. M.; Guimarães, O. R.; Geller, M.; Paoli, F.; Fonseca, A. S.

2016-06-01

Low-level lasers have been used worldwide to treat a number of diseases, pain relief, and wound healing. Some studies demonstrated that low-level laser radiations induce effects depending on the physiological state and DNA repair mechanisms of cells. In this work we evaluated the effects of low-level red and infrared lasers on Escherichia coli cells deficient in SOS responses submitted to heat stress. Exponential and stationary E. coli cultures of wild type (AB1157), RecA deficient (AB2463) and LexA deficient (AB2494), both SOS response deficient, were exposed to low-level red and infrared lasers at different fluences and submitted to heat stress (42 °C, 20 min). After that, cell survival and morphology were evaluated. Previous exposure to red, but not infrared lasers, increases survival fractions and decreases the area ratios of E. coli AB1157 cells submitted to heat stress. Our research suggests that a low-level red laser increases cell viability and protects cells from morphological alteration in E. coli cultures submitted to heat stress depending on laser wavelength and SOS response.

DELLA proteins modulate Arabidopsis defences induced in response to caterpillar herbivory

PubMed Central

Bede, Jacqueline C.

2014-01-01

Upon insect herbivory, many plant species change the direction of metabolic flux from growth into defence. Two key pathways modulating these processes are the gibberellin (GA)/DELLA pathway and the jasmonate pathway. In this study, the effect of caterpillar herbivory on plant-induced responses was compared between wild-type Arabidopsis thaliana (L.) Heynh. and quad-della mutants that have constitutively elevated GA responses. The labial saliva (LS) of caterpillars of the beet armyworm, Spodoptera exigua, is known to influence induced plant defence responses. To determine the role of this herbivore cue in determining metabolic shifts, plants were subject to herbivory by caterpillars with intact or impaired LS secretions. In both wild-type and quad-della plants, a jasmonate burst is an early response to caterpillar herbivory. Negative growth regulator DELLA proteins are required for the LS-mediated suppression of hormone levels. Jasmonate-dependent marker genes are induced in response to herbivory independently of LS, with the exception of AtPDF1.2 that showed LS-dependent expression in the quad-della mutant. Early expression of the salicylic acid (SA)-marker gene, AtPR1, was not affected by herbivory which also reflected SA hormone levels; however, this gene showed LS-dependent expression in the quad-della mutant. DELLA proteins may positively regulate glucosinolate levels and suppress laccase-like multicopper oxidase activity in response to herbivory. The present results show a link between DELLA proteins and early, induced plant defences in response to insect herbivory; in particular, these proteins are necessary for caterpillar LS-associated attenuation of defence hormones. PMID:24399173

Phosphorus, zinc, and boron influence yield components in Earliglow strawberry

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

May, G.M.; Pritts, M.P.

1993-01-01

The main effects and interactions of soil-applied P, B, and Zn on yield and its components were examined in the field at two pH levels with Earliglow' strawberries (Fragaria ananassa Duch.). Applied nutrients had significant effects on several yield components, but responses depended on the levels of other nutrients or the soil pH. At a soil pH of 5.5, yield responded linearly to B and quadratically to P. At pH 6.5, P interacted with B and Zn. Fruit count per inflorescence was the yield component most strongly associated with yield, followed by individual fruit weight. However, these two yield componentsmore » responded differently to soil-applied nutrients. Foliar nutrient levels generally did not increase with the amount of applied nutrient, but often an applied nutrient had a strong effect on the level of another nutrient. Leaf nutrient levels were often correlated with fruit levels, but foliar and fruit levels at harvest were not related to reproductive performance. The study identifies some of the problems inherent in using foliar nutrient levels to predict a yield response and demonstrates how plant responses to single nutrients depend on soil chemistry and the presence of other nutrients.« less

Wavelength dependence of intracellular nitric oxide levels in hTERT-RPE cells in vitro

NASA Astrophysics Data System (ADS)

Pope, Nathaniel J.; Powell, Samantha M.; Wigle, Jeffrey C.

2018-02-01

Photobiomodulation (PBM) refers to the beneficial effects of low doses of light whether mediating therapeutic effects for pathophysiological processes, or stimulating resistance to physiological challenges. While much is known about beneficial outcomes, our understanding of the molecular mechanisms underlying these observed effects is still limited. It has been hypothesized that increases in ATP stimulate downstream signaling through transcription factors. However, it is also known that PBM can induce elevated levels of nitric oxide (NO) in cells, which is thought to occur by release of NO bound to cytochrome-c oxidase (COX). NO is a powerful signaling molecule involved in a host of biological responses; however, the mechanisms of NO production and the role of NO in the PBM response have received little attention. Utilizing human retinal pigmented epithelium cells (RPE) in vitro, coupled with a multi-laser exposure set-up, we have begun to systematically investigate the mechanism of NO production and function in the PBM response. Our data indicates that while NO levels are elevated following single exposures to 447, 532, 635 or 808 nm, the strength of the response is wavelength-dependent, and the response can be modulated by sequential exposures to two different wavelengths. Additionally, this wavelength-dependent rise in NO is independent of the function of nitric oxide synthase, and highly dependent on the source of electrons feeding the electron transport chain of the light-exposed cells. In sum, these results provide a roadmap for interrogating the molecular mechanisms of PBM, and provide novel tools and methods for dissecting NO signaling networks.

A Modal Model to Simulate Typical Structural Dynamic Nonlinearity [PowerPoint

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

Mayes, Randall L.; Pacini, Benjamin Robert; Roettgen, Dan

2016-01-01

Some initial investigations have been published which simulate nonlinear response with almost traditional modal models: instead of connecting the modal mass to ground through the traditional spring and damper, a nonlinear Iwan element was added. This assumes that the mode shapes do not change with amplitude and there are no interactions between modal degrees of freedom. This work expands on these previous studies. An impact experiment is performed on a structure which exhibits typical structural dynamic nonlinear response, i.e. weak frequency dependence and strong damping dependence on the amplitude of vibration. Use of low level modal test results in combinationmore » with high level impacts are processed using various combinations of modal filtering, the Hilbert Transform and band-pass filtering to develop response data that are then fit with various nonlinear elements to create a nonlinear pseudo-modal model. Simulations of forced response are compared with high level experimental data for various nonlinear element assumptions.« less

A Modal Model to Simulate Typical Structural Dynamic Nonlinearity

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

Pacini, Benjamin Robert; Mayes, Randall L.; Roettgen, Daniel R

2015-10-01

Some initial investigations have been published which simulate nonlinear response with almost traditional modal models: instead of connecting the modal mass to ground through the traditional spring and damper, a nonlinear Iwan element was added. This assumes that the mode shapes do not change with amplitude and there are no interactions between modal degrees of freedom. This work expands on these previous studies. An impact experiment is performed on a structure which exhibits typical structural dynamic nonlinear response, i.e. weak frequency dependence and strong damping dependence on the amplitude of vibration. Use of low level modal test results in combinationmore » with high level impacts are processed using various combinations of modal filtering, the Hilbert Transform and band-pass filtering to develop response data that are then fit with various nonlinear elements to create a nonlinear pseudo-modal model. Simulations of forced response are compared with high level experimental data for various nonlinear element assumptions.« less

Response of single bacterial cells to stress gives rise to complex history dependence at the population level

PubMed Central

Mathis, Roland; Ackermann, Martin

2016-01-01

Most bacteria live in ever-changing environments where periods of stress are common. One fundamental question is whether individual bacterial cells have an increased tolerance to stress if they recently have been exposed to lower levels of the same stressor. To address this question, we worked with the bacterium Caulobacter crescentus and asked whether exposure to a moderate concentration of sodium chloride would affect survival during later exposure to a higher concentration. We found that the effects measured at the population level depended in a surprising and complex way on the time interval between the two exposure events: The effect of the first exposure on survival of the second exposure was positive for some time intervals but negative for others. We hypothesized that the complex pattern of history dependence at the population level was a consequence of the responses of individual cells to sodium chloride that we observed: (i) exposure to moderate concentrations of sodium chloride caused delays in cell division and led to cell-cycle synchronization, and (ii) whether a bacterium would survive subsequent exposure to higher concentrations was dependent on the cell-cycle state. Using computational modeling, we demonstrated that indeed the combination of these two effects could explain the complex patterns of history dependence observed at the population level. Our insight into how the behavior of single cells scales up to processes at the population level provides a perspective on how organisms operate in dynamic environments with fluctuating stress exposure. PMID:26960998

Predicting the practice effects on the blood oxygenation level-dependent (BOLD) function of fMRI in a symbolic manipulation task

NASA Astrophysics Data System (ADS)

Qin, Yulin; Sohn, Myeong-Ho; Anderson, John R.; Stenger, V. Andrew; Fissell, Kate; Goode, Adam; Carter, Cameron S.

2003-04-01

Based on adaptive control of thought-rational (ACT-R), a cognitive architecture for cognitive modeling, researchers have developed an information-processing model to predict the blood oxygenation level-dependent (BOLD) response of functional MRI in symbol manipulation tasks. As an extension of this research, the current event-related functional MRI study investigates the effect of relatively extensive practice on the activation patterns of related brain regions. The task involved performing transformations on equations in an artificial algebra system. This paper shows that the base-level activation learning in the ACT-R theory can predict the change of the BOLD response in practice in a left prefrontal region reflecting retrieval of information. In contrast, practice has relatively little effect on the form of BOLD response in the parietal region reflecting imagined transformations to the equation or the motor region reflecting manual programming.

Down-regulation of respiration in pear fruit depends on temperature.

PubMed

Ho, Quang Tri; Hertog, Maarten L A T M; Verboven, Pieter; Ambaw, Alemayehu; Rogge, Seppe; Verlinden, Bert E; Nicolaï, Bart M

2018-04-09

The respiration rate of plant tissues decreases when the amount of available O2 is reduced. There is, however, a debate on whether the respiration rate is controlled either by diffusion limitation of oxygen or through regulatory processes at the level of the transcriptome. We used experimental and modelling approaches to demonstrate that both diffusion limitation and metabolic regulation affect the response of respiration of bulky plant organs such as fruit to reduced O2 levels in the surrounding atmosphere. Diffusion limitation greatly affects fruit respiration at high temperature, but at low temperature respiration is reduced through a regulatory process, presumably a response to a signal generated by a plant oxygen sensor. The response of respiration to O2 is time dependent and is highly sensitive, particularly at low O2 levels in the surrounding atmosphere. Down-regulation of the respiration at low temperatures may save internal O2 and relieve hypoxic conditions in the fruit.

Inter-individual variability in cortical excitability and motor network connectivity following multiple blocks of rTMS

PubMed Central

Nettekoven, Charlotte; Volz, Lukas J.; Leimbach, Martha; Pool, Eva-Maria; Rehme, Anne K.; Eickhoff, Simon B.; Fink, Gereon R.; Grefkes, Christian

2016-01-01

The responsiveness to non-invasive neuromodulation protocols shows high inter-individual variability, the reasons of which remain poorly understood. We here tested whether the response to intermittent theta-burst stimulation (iTBS) – an effective repetitive transcranial magnetic stimulation (rTMS) protocol for increasing cortical excitability – depends on network properties of the cortical motor system. We furthermore investigated whether the responsiveness to iTBS is dose-dependent. To this end, we used a sham-stimulation controlled, single-blinded within-subject design testing for the relationship between iTBS aftereffects and (i) motor-evoked potentials (MEPs) as well as (ii) resting-state functional connectivity (rsFC) in 16 healthy subjects. In each session, three blocks of iTBS were applied, separated by 15 min. We found that non-responders (subjects not showing an MEP increase of ≥10% after one iTBS block) featured stronger rsFC between the stimulated primary motor cortex (M1) and premotor areas before stimulation compared to responders. However, only the group of responders showed increases in rsFC and MEPs, while most non-responders remained close to baseline levels after all three blocks of iTBS. Importantly, there was still a large amount of variability in both groups. Our data suggest that responsiveness to iTBS at the local level (i.e., M1 excitability) depends upon the pre-interventional network connectivity of the stimulated region. Of note, increasing iTBS dose did not turn non-responders into responders. The finding that higher levels of pre-interventional connectivity precluded a response to iTBS could reflect a ceiling effect underlying non-responsiveness to iTBS at the systems level. PMID:26052083

Inter-individual variability in cortical excitability and motor network connectivity following multiple blocks of rTMS.

PubMed

Nettekoven, Charlotte; Volz, Lukas J; Leimbach, Martha; Pool, Eva-Maria; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

2015-09-01

The responsiveness to non-invasive neuromodulation protocols shows high inter-individual variability, the reasons of which remain poorly understood. We here tested whether the response to intermittent theta-burst stimulation (iTBS) - an effective repetitive transcranial magnetic stimulation (rTMS) protocol for increasing cortical excitability - depends on network properties of the cortical motor system. We furthermore investigated whether the responsiveness to iTBS is dose-dependent. To this end, we used a sham-stimulation controlled, single-blinded within-subject design testing for the relationship between iTBS aftereffects and (i) motor-evoked potentials (MEPs) as well as (ii) resting-state functional connectivity (rsFC) in 16 healthy subjects. In each session, three blocks of iTBS were applied, separated by 15min. We found that non-responders (subjects not showing an MEP increase of ≥10% after one iTBS block) featured stronger rsFC between the stimulated primary motor cortex (M1) and premotor areas before stimulation compared to responders. However, only the group of responders showed increases in rsFC and MEPs, while most non-responders remained close to baseline levels after all three blocks of iTBS. Importantly, there was still a large amount of variability in both groups. Our data suggest that responsiveness to iTBS at the local level (i.e., M1 excitability) depends upon the pre-interventional network connectivity of the stimulated region. Of note, increasing iTBS dose did not turn non-responders into responders. The finding that higher levels of pre-interventional connectivity precluded a response to iTBS could reflect a ceiling effect underlying non-responsiveness to iTBS at the systems level. Copyright © 2015 Elsevier Inc. All rights reserved.

Size-mediated response to public cues of predation risk in a tropical stream fish.

PubMed

Elvidge, C K; Ramnarine, I W; Godin, J-G J; Brown, G E

2010-11-01

In order to investigate any size-dependent differences between behavioural patterns, wild-caught Hart's rivulus Rivulus hartii of varying sizes were exposed to chemical alarm cues extracted from the skin of conspecifics or heterospecific Poecilia reticulata, or a tank water control, in a series of laboratory trials. In response to conspecific alarm cues, R. hartii subjects of the range of body sizes tested exhibited consistent, size-independent antipredator behaviours that were characterized by decreased locomotory activity and foraging levels and increased refuging behaviour. Conversely, focal R. hartii demonstrated significant size-dependent trends in response to heterospecific alarm cues, with smaller individuals exhibiting antipredator responses and larger individuals shifting their behaviour to increased levels of activity consistent with a foraging, or predatory, response. These results show that the behavioural responses of individual R. hartii to publicly available chemical alarm cues from heterospecifics are mediated by the size of the receiver. © 2010 The Authors. Journal of Fish Biology © 2010 The Fisheries Society of the British Isles.

Exercise, oxidants, and antioxidants change the shape of the bell-shaped hormesis curve.

PubMed

Radak, Zsolt; Ishihara, Kazunari; Tekus, Eva; Varga, Csaba; Posa, Aniko; Balogh, Laszlo; Boldogh, Istvan; Koltai, Erika

2017-08-01

It is debated whether exercise-induced ROS production is obligatory to cause adaptive response. It is also claimed that antioxidant treatment could eliminate the adaptive response, which appears to be systemic and reportedly reduces the incidence of a wide range of diseases. Here we suggest that if the antioxidant treatment occurs before the physiological function-ROS dose-response curve reaches peak level, the antioxidants can attenuate function. On the other hand, if the antioxidant treatment takes place after the summit of the bell-shaped dose response curve, antioxidant treatment would have beneficial effects on function. We suggest that the effects of antioxidant treatment are dependent on the intensity of exercise, since the adaptive response, which is multi pathway dependent, is strongly influenced by exercise intensity. It is further suggested that levels of ROS concentration are associated with peak physiological function and can be extended by physical fitness level and this could be the basis for exercise pre-conditioning. Physical inactivity, aging or pathological disorders increase the sensitivity to oxidative stress by altering the bell-shaped dose response curve. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Block-Dependent Sedation during Epidural Anaesthesia is Associated with Delayed Brainstem Conduction

PubMed Central

Wadhwa, Anupama; Shah, Yunus M.; Lin, Chum-Ming; Haugh, Gilbert S.; Sessler, Daniel I.

2005-01-01

Neuraxial anaesthesia produces a sedative and anesthetic-sparing effect. Recent evidence suggests that spinal cord anaesthesia modifies reticulo-thalamo-cortical arousal by decreasing afferent sensory transmission. We hypothesized that epidural anaesthesia produces sensory deafferentation-dependent sedation that is associated with impairment of brainstem transmission. We used brainstem auditory evoked potentials (BAEP) to evaluate reticular function in 11 volunteers. Epidural anaesthesia was induced with 2% 2-chloroprocaine. Hemodynamic and respiratory responses, sensory block level, sedation depth and BAEP were assessed throughout induction and resolution of epidural anaesthesia. Sedation was evaluated using verbal rating score (VRS), observer's assessment alertness/sedation (OAA/S) score, and bispectral index (BIS). Prediction probability (PK) was used to associate sensory block with sedation, as well as BIS with other sedation measures. Spearman rank order correlation was used to associate block level and sedation with the absolute and interpeak BAEP latencies. Sensory block level significantly predicted VRS (PK = 0.747), OAA/S score (PK = 0.748) and BIS. Bispectral index predicted VRS and OAA/S score (PK = 0.728). The latency of wave III of BAEP significantly correlated with sedation level (rho = 0.335, P < 0.01) and sensory block (rho = 0.394, P < 0.01). The other BAEP parameters did not change during epidural anaesthesia. Hemodynamic and respiratory responses remained stable throughout the study. Sedation during epidural anaesthesia depends on sensory block level and is associated with detectable block-dependent alterations in the brainstem auditory evoked responses. Sensory deafferentation may reduce CNS alertness through mechanisms related to brainstem neural activity. PMID:15220178

Contrasting neural effects of aging on proactive and reactive response inhibition.

PubMed

Bloemendaal, Mirjam; Zandbelt, Bram; Wegman, Joost; van de Rest, Ondine; Cools, Roshan; Aarts, Esther

2016-10-01

Two distinct forms of response inhibition may underlie observed deficits in response inhibition in aging. We assessed whether age-related neurocognitive impairments in response inhibition reflect deficient reactive inhibition (outright stopping) or also deficient proactive inhibition (anticipatory response slowing), which might be particularly evident with high information load. We used functional magnetic resonance imaging in young (n = 25, age range 18-32) and older adults (n = 23, 61-74) with a stop-signal task. Relative to young adults, older adults exhibited impaired reactive inhibition (i.e., longer stop-signal reaction time) and increased blood oxygen level-dependent (BOLD) signal for successful versus unsuccessful inhibition in the left frontal cortex and cerebellum. Furthermore, older adults also exhibited impaired proactive slowing, but only as a function of information load. This load-dependent behavioral deficit was accompanied by a failure to increase blood oxygen level-dependent (BOLD) signal under high information load in lateral frontal cortex, presupplementary motor area and striatum. Our findings suggest that inhibitory deficits in older adults are caused both by reduced stopping abilities and by diminished preparation capacity during information overload. Copyright © 2016 Elsevier Inc. All rights reserved.

Item Response Theory analysis of Fagerström Test for Cigarette Dependence.

PubMed

Svicher, Andrea; Cosci, Fiammetta; Giannini, Marco; Pistelli, Francesco; Fagerström, Karl

2018-02-01

The Fagerström Test for Cigarette Dependence (FTCD) and the Heaviness of Smoking Index (HSI) are the gold standard measures to assess cigarette dependence. However, FTCD reliability and factor structure have been questioned and HSI psychometric properties are in need of further investigations. The present study examined the psychometrics properties of the FTCD and the HSI via the Item Response Theory. The study was a secondary analysis of data collected in 862 Italian daily smokers. Confirmatory factor analysis was run to evaluate the dimensionality of FTCD. A Grade Response Model was applied to FTCD and HSI to verify the fit to the data. Both item and test functioning were analyzed and item statistics, Test Information Function, and scale reliabilities were calculated. Mokken Scale Analysis was applied to estimate homogeneity and Loevinger's coefficients were calculated. The FTCD showed unidimensionality and homogeneity for most of the items and for the total score. It also showed high sensitivity and good reliability from medium to high levels of cigarette dependence, although problems related to some items (i.e., items 3 and 5) were evident. HSI had good homogeneity, adequate item functioning, and high reliability from medium to high levels of cigarette dependence. Significant Differential Item Functioning was found for items 1, 4, 5 of the FTCD and for both items of HSI. HSI seems highly recommended in clinical settings addressed to heavy smokers while FTCD would be better used in smokers with a level of cigarette dependence ranging between low and high. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oxidative stress mediated toxicity of TiO2 nanoparticles after a concentration and time dependent exposure of the aquatic macrophyte Hydrilla verticillata.

PubMed

Spengler, Annette; Wanninger, Lena; Pflugmacher, Stephan

2017-09-01

The present study focused on oxidative stress effects in the aquatic macrophyte Hydrilla verticillata after exposure to titanium dioxide nanoparticles (TiO 2 -NPs). Experiments were conducted with different TiO 2 -NPs and concentrations (0.1 mg/L and 10 mg/L) in a time-dependent manner (0 h, 24 h, 48 h, 96 h, 168 h). To assess various levels of the oxidative stress response in H. verticillata, the level of hydrogen peroxide (H 2 O 2 ), the ratio of reduced to oxidized glutathione (GSH/GSSG), and activities of the antioxidative enzymes catalase (CAT) and glutathione reductase (GR) were evaluated. Study results imply oxidative stress effects after TiO 2 -NP exposure as adaptations in plant metabolism became apparent to counteract increased ROS formation. All TiO 2 -NPs caused elevated activities of the enzymes CAT and GR. Moreover, decreased ratios of GSH/GSSG indicated an activation of GSH-dependent pathways counteracting ROS formation. Plants exposed to a bulk-sized control revealed a size-dependent influence on the antioxidative stress response. As H 2 O 2 level increases were solely detected after exposure to 10 mg/L TiO 2 -NPs and nano-exposed plants showed normalization in its antioxidative stress response after 168h of exposure, it can be suggested that macrophytes are able to cope with currently predicted low-level exposures to TiO 2 -NPs. Copyright © 2017 Elsevier B.V. All rights reserved.

Evoked-potential recovery during double click stimulation in a whale: a possibility of biosonar automatic gain control.

PubMed

Supin, Alexander Ya; Nachtigall, Paul E; Breese, Marlee

2007-01-01

False killer whale Pseudorca crassidens auditory brainstem responses (ABR) were recorded using a double-click stimulation paradigm specifically measuring the recovery of the second response (to the test click) as a function of the inter-click interval (ICI) at various levels of the conditioning and test click. At all click intensities, the slopes of recovery functions were almost constant: 0.6-0.8 microV per ICI decade. Therefore, even when the conditioning-to-test-click level ratio was kept constant, the duration of recovery was intensity-dependent: The higher intensity the longer the recovery. The conditioning-to-test-click level ratio strongly influenced the recovery time: The higher the ratio, the longer the recovery. The dependence was almost linear using a logarithmic ICI scale with a rate of 25-30 dB per ICI decade. These data were used for modeling the interaction between the emitted click and the echo during echolocation, assuming that the two clicks simulated the transmitted and echo clicks. This simulation showed that partial masking of the echo by the preceding emitted click may explain the independence of echo-response amplitude of target distance. However, the distance range where this mechanism is effective depends on the emitted click level: The higher the level, the greater the range. @ 2007 Acoustical Society of America.

Dopamine D1 receptor-dependent regulation of extracellular citrulline level in the rat nucleus accumbens during conditioned fear response.

PubMed

Saulskaya, Natalia B; Fofonova, Nellia V; Sudorghina, Polina V; Saveliev, Sergey A

2008-08-01

Nucleus accumbens (N.Acc) contains a subclass of nitric oxide (NO)-generating interneurons that are presumably regulated by the dopamine input. Receptor mechanisms underlying dopamine-NO interaction in the N.Acc are poorly understood. In the current study, we used in vivo microdialysis combined with high-performance liquid chromatography to examine participation of dopamine D1 receptors in regulation of extracellular levels of citrulline (an NO co-product) in the medial N.Acc of Sprague-Dawley rats during both pharmacological challenge and a conditioned fear response. The intraaccumbal infusion of the D1 receptor agonist SKF-38393 (100-500 microM) increased dose-dependently the local dialysate citrulline levels. The SKF-38393-induced increase in extracellular citrulline was prevented by intraaccumbal infusions of 500 microM 7-nitroindazole, a neuronal NO synthase inhibitor. In behavioral microdialysis experiment, the accumbal levels of extracellular citrulline markedly increased in rats given a mild footshock paired with tone. The presentation of the tone previously paired with footshock (the conditioned fear response) produced a "conditioned" rise of extracellular citrulline levels in the N.Acc which was attenuated by intraaccumbal infusion of 100 microM SCH-23390, a dopamine D1 receptor antagonist, and prevented by intraaccumbal infusion of 500 microM 7-nitroindazole. The results suggest that in the N.Acc, the dopamine D1 receptors might regulate the neuronal NO synthase activity; this dopamine-dependent mechanism seems to participate in activation of the neuronal NO synthase and probably NO formation in this brain area during the conditioned fear response.

Dissociations between behavioural and functional magnetic resonance imaging-based evaluations of cognitive function after brain injury

PubMed Central

Bardin, Jonathan C.; Fins, Joseph J.; Katz, Douglas I.; Hersh, Jennifer; Heier, Linda A.; Tabelow, Karsten; Dyke, Jonathan P.; Ballon, Douglas J.; Schiff, Nicholas D.

2011-01-01

Functional neuroimaging methods hold promise for the identification of cognitive function and communication capacity in some severely brain-injured patients who may not retain sufficient motor function to demonstrate their abilities. We studied seven severely brain-injured patients and a control group of 14 subjects using a novel hierarchical functional magnetic resonance imaging assessment utilizing mental imagery responses. Whereas the control group showed consistent and accurate (for communication) blood-oxygen-level-dependent responses without exception, the brain-injured subjects showed a wide variation in the correlation of blood-oxygen-level-dependent responses and overt behavioural responses. Specifically, the brain-injured subjects dissociated bedside and functional magnetic resonance imaging-based command following and communication capabilities. These observations reveal significant challenges in developing validated functional magnetic resonance imaging-based methods for clinical use and raise interesting questions about underlying brain function assayed using these methods in brain-injured subjects. PMID:21354974

Equilibrium finite-frequency noise of an interacting mesoscopic capacitor studied in time-dependent density functional theory

NASA Astrophysics Data System (ADS)

Dittmann, Niklas; Splettstoesser, Janine; Helbig, Nicole

2018-03-01

We calculate the frequency-dependent equilibrium noise of a mesoscopic capacitor in time-dependent density functional theory (TDDFT). The capacitor is modeled as a single-level quantum dot with on-site Coulomb interaction and tunnel coupling to a nearby reservoir. The noise spectra are derived from linear-response conductances via the fluctuation-dissipation theorem. Thereby, we analyze the performance of a recently derived exchange-correlation potential with time-nonlocal density dependence in the finite-frequency linear-response regime. We compare our TDDFT noise spectra with real-time perturbation theory and find excellent agreement for noise frequencies below the reservoir temperature.

Encoding of sound envelope transients in the auditory cortex of juvenile rats and adult rats.

PubMed

Lu, Qi; Jiang, Cuiping; Zhang, Jiping

2016-02-01

Accurate neural processing of time-varying sound amplitude and spectral information is vital for species-specific communication. During postnatal development, cortical processing of sound frequency undergoes progressive refinement; however, it is not clear whether cortical processing of sound envelope transients also undergoes age-related changes. We determined the dependence of neural response strength and first-spike latency on sound rise-fall time across sound levels in the primary auditory cortex (A1) of juvenile (P20-P30) rats and adult (8-10 weeks) rats. A1 neurons were categorized as "all-pass", "short-pass", or "mixed" ("all-pass" at high sound levels to "short-pass" at lower sound levels) based on the normalized response strength vs. rise-fall time functions across sound levels. The proportions of A1 neurons within each of the three categories in juvenile rats were similar to that in adult rats. In general, with increasing rise-fall time, the average response strength decreased and the average first-spike latency increased in A1 neurons of both groups. At a given sound level and rise-fall time, the average normalized neural response strength did not differ significantly between the two age groups. However, the A1 neurons in juvenile rats showed greater absolute response strength, longer first-spike latency compared to those in adult rats. In addition, at a constant sound level, the average first-spike latency of juvenile A1 neurons was more sensitive to changes in rise-fall time. Our results demonstrate the dependence of the responses of rat A1 neurons on sound rise-fall time, and suggest that the response latency exhibit some age-related changes in cortical representation of sound envelope rise time. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Strategics of medical centers and regional hospitals in response to new labour insurance fee schedule].

PubMed

Wang, S C; Sheen, P C; Ko, Y C

1993-02-01

The purpose of this paper is to evaluate the medical centers and regional hospitals, strategic response to the implementation of new labour insurance fee schedule. This survey selects fifty-one medical centers and regional hospitals, with the response rate of 92.73%. This questionnaire was developed and evaluated by the authors and mailed to the questionnaire response by hospital's director or relative department director. We have selected Shortell et al. (1985) theory as the framework for evaluating and explaining hospital response to regulation environment (ex: change in the reimbursement system) at institutional-level response (ex: hospital association activity aimed at influencing regulation), managerial-level response (ex: increased physician participation in hospital-wide decision making; starting or expanding a planning department) and technical-level response (ex: shared clinical services such as lab., X-ray, pharmacy). The result found that hospitals with the characteristics as non-public ownership, medical centers, bigger size, and more administrative staff are more inclined to adopt institutional-level response. And a technical-level response occurs to hospital when market competibility becomes more intense which leads to higher reimbursement resource dependency.

Racial bias in neural response to others' pain is reduced with other-race contact.

PubMed

Cao, Yuan; Contreras-Huerta, Luis Sebastian; McFadyen, Jessica; Cunnington, Ross

2015-09-01

Observing the pain of others has been shown to elicit greater activation in sensory and emotional areas of the brain suggested to represent a neural marker of empathy. This modulation of brain responses to others' pain is dependent on the race of the observed person, such that observing own-race people in pain is associated with greater activity in the anterior cingulate and bilateral insula cortices compared to other-race people. Importantly, it is not known how this racial bias to pain in other-race individuals might change over time in new immigrants or might depend on the level and quality of contact with people of the other-race. We investigated these issues by recruiting Chinese students who had first arrived in Australia within the past 6 months to 5 years and assessing their level of contact with other races across different social contexts using comprehensive rating scales. During fMRI, participants observed videos of own-race/other-race individuals, as well as own-group/other-group individuals, receiving painful or non-painful touch. The typical racial bias in neural responses to observed pain was evident, whereby activation in the anterior cingulate cortex (ACC) was greater for pain in own-race compared to other-race people. Crucially, activation in the anterior cingulate to pain in other races increased significantly with the level of contact participants reported with people of the other race. Importantly, this correlation did not depend on the closeness of contact or personal relationships, but simply on the overall level of experience with people of the other race in their every-day environment. Racial bias in neural responses to others' pain, as a neural marker of empathy, therefore changes with experience in new immigrants at least within 5 years of arrival in the new society and, crucially, depends on the level of contact with people of the other race in every-day life contexts. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Threshold and Beyond: Modeling The Intensity Dependence of Auditory Responses

PubMed Central

2007-01-01

In many studies of auditory-evoked responses to low-intensity sounds, the response amplitude appears to increase roughly linearly with the sound level in decibels (dB), corresponding to a logarithmic intensity dependence. But the auditory system is assumed to be linear in the low-intensity limit. The goal of this study was to resolve the seeming contradiction. Based on assumptions about the rate-intensity functions of single auditory-nerve fibers and the pattern of cochlear excitation caused by a tone, a model for the gross response of the population of auditory nerve fibers was developed. In accordance with signal detection theory, the model denies the existence of a threshold. This implies that regarding the detection of a significant stimulus-related effect, a reduction in sound intensity can always be compensated for by increasing the measurement time, at least in theory. The model suggests that the gross response is proportional to intensity when the latter is low (range I), and a linear function of sound level at higher intensities (range III). For intensities in between, it is concluded that noisy experimental data may provide seemingly irrefutable evidence of a linear dependence on sound pressure (range II). In view of the small response amplitudes that are to be expected for intensity range I, direct observation of the predicted proportionality with intensity will generally be a challenging task for an experimenter. Although the model was developed for the auditory nerve, the basic conclusions are probably valid for higher levels of the auditory system, too, and might help to improve models for loudness at threshold. PMID:18008105

Community-Dwelling Cocaine-Dependent Men and Women Respond Differently to Social Stressors versus Cocaine Cues

PubMed Central

Waldrop, Angela E.; Price, Kimber L.; DeSantis, Stacia M.; Simpson, Annie N.; Back, Sudie E.; McRae, Aimee L.; Spratt, Eve G.; Kreek, Mary Jeanne; Brady, Kathleen T.

2009-01-01

Summary There are likely to be gender differences in determinants of relapse to drug use following abstinence in cocaine-dependent individuals. Cocaine-dependent women are more likely to attribute relapse to negative emotional states and interpersonal conflict. Cocaine dependence has also been linked to dysregulation of stress response and the hypothalamic pituitary adrenal (HPA) axis which may differ between genders. Subjective and HPA axis responses to a social evaluative stressor, the Trier Social Stress Test (TRIER), and in vivo cocaine-related cues were examined in the present study. Results There were no gender differences in magnitude of craving responses to the TRIER or the CUE. Both genders had a greater craving response to the CUE than to the TRIER, but the magnitude of the difference was greater for men than women (p=0.04). Cocaine-dependent subjects, compared to the control group, had significantly higher response throughout the TRIER (p<0.0001) and CUE (p<0.0001) testing sessions. There were no gender differences and no gender by cocaine interaction for ACTH responses to the TRIER, although women had lower baseline ACTH (p=0.049). On the CUE task, in contrast, female cocaine-dependent subjects had a more blunted ACTH response than did the other three groups (p=0.02). Female cocaine-dependent subjects also had a lower odds of a positive cortisol response to the TRIER as compared to the other three groups (OR=0.84, 95% CI=[0.02, 1.01]). During the CUE task, cocaine-dependent subjects had overall higher mean cortisol levels (p=0.0001), and higher odds of demonstrating a positive cortisol response to the CUE (OR=2.61, 95% CI=[1.11, 6.11]). No gender differences were found in ACTH responses to the CUE. The results are reviewed in the context of the existing literature on gender differences in cocaine dependence and potential implications for treatment are discussed. PMID:20004523

Glutathione maintenance is crucial for survival of melanocytes after exposure to rhododendrol.

PubMed

Kondo, Masatoshi; Kawabata, Keigo; Sato, Kohji; Yamaguchi, Sayuri; Hachiya, Akira; Takahashi, Yoshito; Inoue, Shintaro

2016-09-01

Rhododendrol is a phenolic compound that shows a tyrosinase-dependent toxicity for melanocytes and occasionally induces a vitiligo-like skin depigmentation. The post-tyrosinase mechanisms determining melanocyte death or survival, however, are far from clear. Here, we find that rhododendrol treatment leads to a reduction in the levels of cellular glutathione but also induces a cellular antioxidant response that eventually increases glutathione levels. We further find that rhododendrol toxicity is enhanced when glutathione levels are experimentally reduced and alleviated when glutathione levels are increased. Hence, it appears that the size of the preexisting glutathione pool along with the capacity to supply glutathione via the antioxidant response determines whether melanocytes survive or die after rhododendrol exposure. It is conceivable, therefore, that rhododendrol-induced leukoderma depends on the capacity to maintain appropriate glutathione levels and that enhancement of glutathione levels may preserve a patient's melanocytes and potentially help in repigmentation. © 2016 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.

Pretreatment Differences in BOLD Response to Emotional Faces Correlate with Antidepressant Response to Scopolamine.

PubMed

Furey, Maura L; Drevets, Wayne C; Szczepanik, Joanna; Khanna, Ashish; Nugent, Allison; Zarate, Carlos A

2015-03-28

Faster acting antidepressants and biomarkers that predict treatment response are needed to facilitate the development of more effective treatments for patients with major depressive disorders. Here, we evaluate implicitly and explicitly processed emotional faces using neuroimaging to identify potential biomarkers of treatment response to the antimuscarinic, scopolamine. Healthy participants (n=15) and unmedicated-depressed major depressive disorder patients (n=16) participated in a double-blind, placebo-controlled crossover infusion study using scopolamine (4 μg/kg). Before and following scopolamine, blood oxygen-level dependent signal was measured using functional MRI during a selective attention task. Two stimuli comprised of superimposed pictures of faces and houses were presented. Participants attended to one stimulus component and performed a matching task. Face emotion was modulated (happy/sad) creating implicit (attend-houses) and explicit (attend-faces) emotion processing conditions. The pretreatment difference in blood oxygen-level dependent response to happy and sad faces under implicit and explicit conditions (emotion processing biases) within a-priori regions of interest was correlated with subsequent treatment response in major depressive disorder. Correlations were observed exclusively during implicit emotion processing in the regions of interest, which included the subgenual anterior cingulate (P<.02) and middle occipital cortices (P<.02). The magnitude and direction of differential blood oxygen-level- dependent response to implicitly processed emotional faces prior to treatment reflect the potential to respond to scopolamine. These findings replicate earlier results, highlighting the potential for pretreatment neural activity in the middle occipital cortices and subgenual anterior cingulate to inform us about the potential to respond clinically to scopolamine. Published by Oxford University Press on behalf of CINP 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Acute effects of heroin on negative emotional processing: relation of amygdala activity and stress-related responses.

PubMed

Schmidt, André; Borgwardt, Stefan; Gerber, Hana; Wiesbeck, Gerhard A; Schmid, Otto; Riecher-Rössler, Anita; Smieskova, Renata; Lang, Undine E; Walter, Marc

2014-08-15

Negative emotional states and abnormal stress reactivity are central components in drug addiction. The brain stress system in the amygdala is thought to play a key role in the maintenance of drug dependence through negative reinforcement. Although acute heroin administration was found to reduce anxiety, craving, and stress hormone release, whether these effects are reflected in amygdala activity has not yet been investigated. With a randomized, crossover, double-blind design, saline and heroin were administered to 22 heroin-dependent patients, whereas 17 healthy control subjects were included for the placebo administration only. We used functional magnetic resonance imaging to investigate blood oxygen level-dependent responses during fearful faces processing. Stress reactivity was measured by adrenocorticotropic hormone levels and by cortisol concentrations in serum and saliva 60 min after substance administration. Anxiety and craving levels were assessed with self-report ratings. Heroin administration acutely reduced the left amygdala response to fearful faces relative to the saline injection. Patients receiving saline showed a significantly higher left amygdala response to fearful faces than healthy control subjects, whose activity did not differ from patients receiving heroin. The left amygdala activity correlated significantly with scores on state-anxiety and levels of adrenocorticotropic hormone, serum cortisol, and saliva cortisol among all patients and control subjects. Our results show a direct relation between the acute heroin effects on stress-related emotions, stress reactivity, and left amygdala response to negative facial expressions. These findings provide new insights into the mechanisms underlying negative reinforcement in heroin addiction and the effects of regular heroin substitution. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

Poly(ADP-ribose) polymerase-1 (Parp-1)-deficient mice demonstrate abnormal antibody responses

PubMed Central

Ambrose, Helen E; Willimott, Shaun; Beswick, Richard W; Dantzer, Françoise; de Murcia, Josiane Ménissier; Yelamos, José; Wagner, Simon D

2009-01-01

Poly(ADP-ribosylation) of acceptor proteins is an epigenetic modification involved in DNA strand break repair, recombination and transcription. Here we provide evidence for the involvement of poly(ADP-ribose) polymerase-1 (Parp-1) in antibody responses. Parp-1−/− mice had increased numbers of T cells and normal numbers of total B cells. Marginal zone B cells were mildly reduced in number, and numbers of follicular B cells were preserved. There were abnormal levels of basal immunoglobulins, with reduced levels of immunoglobulin G2a (IgG2a) and increased levels of IgA and IgG2b. Analysis of specific antibody responses showed that T cell-independent responses were normal but T cell-dependent responses were markedly reduced. Germinal centres were normal in size and number. In vitro purified B cells from Parp-1−/− mice proliferated normally and showed normal IgM secretion, decreased switching to IgG2a but increased IgA secretion. Collectively our results demonstrate that Parp-1 has essential roles in normal T cell-dependent antibody responses and the regulation of isotype expression. We speculate that Parp-1 forms a component of the protein complex involved in resolving the DNA double-strand breaks that occur during class switch recombination. PMID:18778284

Endothelial dysfunction and metabolic control in streptozotocin-induced diabetic rats

PubMed Central

Rodríguez-Mañas, Leocadio; Angulo, Javier; Peiró, Concepción; Llergo, José L; Sánchez-Ferrer, Alberto; López-Dóriga, Pedro; Sánchez-Ferrer, Carlos F

1998-01-01

The aim of this work was to study the influence of the metabolic control, estimated by the levels of glycosylated haemoglobin in total blood samples (HbA1c), in developing vascular endothelial dysfunction in streptozotocin-induced diabetic rats. Four groups of animals with different levels of insulin treatment were established, by determining HbA1c values in 5.5 to 7.4%, 7.5 to 9.4%, 9.5 to 12% and >12%, respectively.The parameters analysed were: (1) the endothelium-dependent relaxations to acetylcholine (ACh) in isolated aorta and mesenteric microvessels; (2) the vasodilator responses to exogenous nitric oxide (NO) in aorta; and (3) the existence of oxidative stress by studying the influence of the free radical scavenger superoxide dismutase (SOD) on the vasodilator responses to both ACh and NO.In both isolated aortic segments and mesenteric microvessels, the endothelium-mediated concentration-dependent relaxant responses elicited by ACh were significantly decreased when the vessels were obtained from diabetic animals but only with HbA1c values higher than 7.5%. There was a high correlation between HbA1c levels and the impairment of ACh-induced relaxations, measured by pD2 values.The concentration-dependent vasorelaxant responses to NO in endothelium-denuded aortic segments were significantly reduced only in vessels from diabetic animals with HbA1c values higher than 7.5%. Again, a very high correlation was found between the HbA1c values and pD2 for NO-evoked responses.In the presence of SOD, the responses to ACh or NO were only increased in the segments from diabetic rats with HbA1c levels higher than 7.5%, but not in those from non-diabetic or diabetic rats with a good metabolic control (HbA1c levels <7.5%).These results suggest the existence of: (1) a close relation between the degree of endothelial dysfunction and the metabolic control of diabetes, estimated by the levels of HbA1c; and (2) an increased production of superoxide anions in the vascular wall of the diabetic rats, which is also related to the metabolic control of the disease. PMID:9605553

Thin-Film Magnetic-Field-Response Fluid-Level Sensor for Non-Viscous Fluids

NASA Technical Reports Server (NTRS)

Woodard, Stanley E.; Shams, Qamar A.; Fox, Robert L.; Taylor, Bryant D.

2008-01-01

An innovative method has been developed for acquiring fluid-level measurements. This method eliminates the need for the fluid-level sensor to have a physical connection to a power source or to data acquisition equipment. The complete system consists of a lightweight, thin-film magnetic-field-response fluid-level sensor (see Figure 1) and a magnetic field response recorder that was described in Magnetic-Field-Response Measurement-Acquisition System (LAR-16908-1), NASA Tech Briefs, Vol. 30, No. 6 (June 2006), page 28. The sensor circuit is a capacitor connected to an inductor. The response recorder powers the sensor using a series of oscillating magnetic fields. Once electrically active, the sensor responds with its own harmonic magnetic field. The sensor will oscillate at its resonant electrical frequency, which is dependent upon the capacitance and inductance values of the circuit.

Dendritic cells' death induced by contact sensitizers is controlled by Nrf2 and depends on glutathione levels

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

El Ali, Zeina

Dendritic cells (DC) are known to play a major role during contact allergy induced by contact sensitizers (CS). Our previous studies showed that Nrf2 was induced in DC and controlled allergic skin inflammation in mice in response to chemicals. In this work, we raised the question of the role of Nrf2 in response to a stress provoked by chemical sensitizers in DC. We used two well-described chemical sensitizers, dinitrochlorobenzene (DNCB) and cinnamaldehyde (CinA), known to have different chemical reactivity and mechanism of action. First, we performed a RT-qPCR array showing that CinA was a higher inducer of immune and detoxificationmore » genes compared to DNCB. Interestingly, in the absence of Nrf2, gene expression was dramatically affected in response to DNCB but was slightly affected in response to CinA. These observations prompted us to study DC's cell death in response to both chemicals. DNCB and CinA increased apoptotic cells and decreased living cells in the absence of Nrf2. The characterization of DC apoptosis induced by both CS involved the mitochondrial-dependent caspase pathway and was regulated via Nrf2 in response to both chemicals. Oxidative stress induced by DNCB, and leading to cell death, was regulated by Nrf2. Unlike CinA, DNCB treatment provoked a significant reduction of intracellular GSH levels and up-regulated bcl-2 gene expression, under the control of Nrf2. This work underlies that chemical reactivity may control Nrf2-dependent gene expression leading to different cytoprotective mechanisms in DC. - Highlights: • Nrf2 controls cell death induced by contact sensitizers in dendritic cells. • DNCB reduced GSH levels and up-regulated bcl-2 gene expression unlike CinA. • Chemical reactivity controls Nrf2-dependent genes having protective effect in DC.« less

The cortisol level and its relationship with depression, stress and anxiety indices in chronic methamphetamine-dependent patients and normal individuals undergoing inguinal hernia surgery.

PubMed

Pirnia, Bijan; Givi, Fatemeh; Roshan, Rasool; Pirnia, Kambiz; Soleimani, Ali Akbar

2016-01-01

Stimulants addition and abuse can cause some functional and morphological changes in the normal function of glands and hormones. Methamphetamine as an addictive stimulant drug affects the Hypothalamic- pituitary-adrenal (HPA) axis and consequently makes some changes in the psychological state of the drug users. The present study aims to examine the relationship between plasma levels of cortisol with depression, stress and anxiety symptoms in chronic methamphetamine-dependent patients and normal individuals who have undergone the inguinal hernia surgery. To meet the purpose of the study, 35 chronic methamphetamine-dependent patients in the active phase of drug abuse and 35 non-users (N=70) who were homogenized regarding the demographic features were purposefully selected from among the patients referred to undergo inguinal hernia surgery since March 15 to June 9, 2015. The participants were then divided into the control and experiment group. The changes in cortisol levels in plasma were measured using Radioimmunoassay (RIA) in three-time series including 0 (upon the induction of anesthesia), 12 and 24 hours after the surgery. Further, three behavioral indices of depression, anxiety and stress were measured using the Depression Anxiety Stress Scale 21 (DASS-21) and then the data were analyzed using t-test and Pearson Correlation coefficient. The plasma level of cortisol in the chronic methamphetamine-dependent patients (experiment group) had a significant increase in 24 hours after surgery (p<0.05). This study showed that cortisol levels in chronic methamphetamine-dependent patients were significantly higher than non-dependent patients in response to alarming events such as inguinal surgery. Changes in cortisol levels were intensified due to a confrontation with the phenomenon of pain and anxiety. In addition, depression index was higher in the chronic methamphetaminedependent patients than that in the non-dependent patients. However, there was no significant relationship between the cortisol level and depression index (p=0.001). The Hypothalamic-pituitary-adrenal (HPA) axis is considered as a key structure in the addiction to simulants, the reason which can explain the faster response of the chronic methamphetamine-dependent patients to the stressors such as surgery.

Response sensitivity of barrel neuron subpopulations to simulated thalamic input.

PubMed

Pesavento, Michael J; Rittenhouse, Cynthia D; Pinto, David J

2010-06-01

Our goal is to examine the relationship between neuron- and network-level processing in the context of a well-studied cortical function, the processing of thalamic input by whisker-barrel circuits in rodent neocortex. Here we focus on neuron-level processing and investigate the responses of excitatory and inhibitory barrel neurons to simulated thalamic inputs applied using the dynamic clamp method in brain slices. Simulated inputs are modeled after real thalamic inputs recorded in vivo in response to brief whisker deflections. Our results suggest that inhibitory neurons require more input to reach firing threshold, but then fire earlier, with less variability, and respond to a broader range of inputs than do excitatory neurons. Differences in the responses of barrel neuron subtypes depend on their intrinsic membrane properties. Neurons with a low input resistance require more input to reach threshold but then fire earlier than neurons with a higher input resistance, regardless of the neuron's classification. Our results also suggest that the response properties of excitatory versus inhibitory barrel neurons are consistent with the response sensitivities of the ensemble barrel network. The short response latency of inhibitory neurons may serve to suppress ensemble barrel responses to asynchronous thalamic input. Correspondingly, whereas neurons acting as part of the barrel circuit in vivo are highly selective for temporally correlated thalamic input, excitatory barrel neurons acting alone in vitro are less so. These data suggest that network-level processing of thalamic input in barrel cortex depends on neuron-level processing of the same input by excitatory and inhibitory barrel neurons.

Response of tobacco to the Pseudomonas syringae pv. Tomato DC3000 is mainly dependent on salicylic acid signaling pathway.

PubMed

Liu, Yang; Wang, Li; Cai, Guohua; Jiang, Shanshan; Sun, Liping; Li, Dequan

2013-07-01

Pseudomonas syringae pv. Tomato DC3000 (Pst DC3000) was the first pathogen to be demonstrated to infect Arabidopsis and to cause disease symptoms in the laboratory setting. However, the defense response to Pst DC3000 was unclear in tobacco. In this report, the expression profiles of twelve defense response-related genes were analyzed after treatment with salicylic acid (SA), jasmonic acid (JA), and pathogen Pst DC3000 by qRT-PCR. According to our results, it could be presented that the genes primarily induced by SA were also induced to higher levels after Pst DC3000 infection. SA accumulation could be induced to a higher level than that of JA after Pst DC3000 infection. In addition, SA could result in hypersensitive response (HR), which did not completely depend on accumulation of reactive oxygen species. These results indicated that tobacco mainly depended on SA signaling pathway rather than on JA signaling pathway in response to Pst DC3000. Further study demonstrated that JA could significantly inhibit the accumulation of SA and the generation of the HR induced by Pst DC3000. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Dengue-Immune Humans Have Higher Levels of Complement-Independent Enhancing Antibody than Complement-Dependent Neutralizing Antibody.

PubMed

Yamanaka, Atsushi; Konishi, Eiji

2017-09-25

Dengue is the most important arboviral disease worldwide. We previously reported that most inhabitants of dengue-endemic countries who are naturally immune to the disease have infection-enhancing antibodies whose in vitro activity does not decrease in the presence of complement (complement-independent enhancing antibodies, or CiEAb). Here, we compared levels of CiEAb and complement-dependent neutralizing antibodies (CdNAb) in dengue-immune humans. A typical antibody dose-response pattern obtained in our assay system to measure the balance between neutralizing and enhancing antibodies showed both neutralizing and enhancing activities depending on serum dilution factor. The addition of complement to the assay system increased the activity of neutralizing antibodies at lower dilutions, indicating the presence of CdNAb. In contrast, similar dose-response curves were obtained with and without complement at higher dilutions, indicating higher levels of CiEAb than CdNAb. For experimental support for the higher CiEAb levels, a cocktail of mouse monoclonal antibodies against dengue virus type 1 was prepared. The antibody dose-response curves obtained in this assay, with or without complement, were similar to those obtained with human serum samples when a high proportion of D1-V-3H12 (an antibody exhibiting only enhancing activity and thus a model for CiEAb) was used in the cocktail. This study revealed higher-level induction of CiEAb than CdNAb in humans naturally infected with dengue viruses.

Interaural Level Difference Dependent Gain Control and Synaptic Scaling Underlying Binaural Computation

PubMed Central

Xiong, Xiaorui R.; Liang, Feixue; Li, Haifu; Mesik, Lukas; Zhang, Ke K.; Polley, Daniel B.; Tao, Huizhong W.; Xiao, Zhongju; Zhang, Li I.

2013-01-01

Binaural integration in the central nucleus of inferior colliculus (ICC) plays a critical role in sound localization. However, its arithmetic nature and underlying synaptic mechanisms remain unclear. Here, we showed in mouse ICC neurons that the contralateral dominance is created by a “push-pull”-like mechanism, with contralaterally dominant excitation and more bilaterally balanced inhibition. Importantly, binaural spiking response is generated apparently from an ipsilaterally-mediated scaling of contralateral response, leaving frequency tuning unchanged. This scaling effect is attributed to a divisive attenuation of contralaterally-evoked synaptic excitation onto ICC neurons with their inhibition largely unaffected. Thus, a gain control mediates the linear transformation from monaural to binaural spike responses. The gain value is modulated by interaural level difference (ILD) primarily through scaling excitation to different levels. The ILD-dependent synaptic scaling and gain adjustment allow ICC neurons to dynamically encode interaural sound localization cues while maintaining an invariant representation of other independent sound attributes. PMID:23972599

Multiscale Evaluation of Thermal Dependence in the Glucocorticoid Response of Vertebrates.

PubMed

Jessop, Tim S; Lane, Meagan L; Teasdale, Luisa; Stuart-Fox, Devi; Wilson, Robbie S; Careau, Vincent; Moore, Ignacio T

2016-09-01

Environmental temperature has profound effects on animal physiology, ecology, and evolution. Glucocorticoid (GC) hormones, through effects on phenotypic performance and life history, provide fundamental vertebrate physiological adaptations to environmental variation, yet we lack a comprehensive understanding of how temperature influences GC regulation in vertebrates. Using field studies and meta- and comparative phylogenetic analyses, we investigated how acute change and broadscale variation in temperature correlated with baseline and stress-induced GC levels. Glucocorticoid levels were found to be temperature and taxon dependent, but generally, vertebrates exhibited strong positive correlations with acute changes in temperature. Furthermore, reptile baseline, bird baseline, and capture stress-induced GC levels to some extent covaried with broadscale environmental temperature. Thus, vertebrate GC function appears clearly thermally influenced. However, we caution that lack of detailed knowledge of thermal plasticity, heritability, and the basis for strong phylogenetic signal in GC responses limits our current understanding of the role of GC hormones in species' responses to current and future climate variation.

Comparative Evaluation of the Auditory Responsiveness of Normal Infants and Profoundly Multihandicapped Children.

ERIC Educational Resources Information Center

Flexer, Carol; Gans, Donald P.

1985-01-01

Responses to sound were observed in two groups of children (one developmentally normal, the other older but profoundly multihandicapped). Results showed no significant differences between groups. In both groups, however, responsiveness was dependent on hearing level and bandwidth but not on meaningfulness. Results support the practice of…

Unruh effect for general trajectories

NASA Astrophysics Data System (ADS)

Obadia, N.; Milgrom, M.

2007-03-01

We consider two-level detectors coupled to a scalar field and moving on arbitrary trajectories in Minkowski space-time. We first derive a generic expression for the response function using a (novel) regularization procedure based on the Feynman prescription that is explicitly causal, and we compare it to other expressions used in the literature. We then use this expression to study, analytically and numerically, the time dependence of the response function in various nonstationarity situations. We show that, generically, the response function decreases like a power in the detector’s level spacing, E, for high E. It is only for stationary worldlines that the response function decays faster than any power law, in keeping with the known exponential behavior for some stationary cases. Under some conditions the (time-dependent) response function for a nonstationary worldline is well approximated by the value of the response function for a stationary worldline having the same instantaneous acceleration, torsion, and hypertorsion. While we cannot offer general conditions for this to apply, we discuss special cases; in particular, the low-energy limit for linear space trajectories.

Stress response of brown pelican nestlings to ectoparasite infestation

USGS Publications Warehouse

Eggert, L.M.F.; Jodice, P.G.R.; O'Reilly, K. M.

2010-01-01

Measurement of corticosterone has become a useful tool for assessing the response of individuals to ecological stressors of interest. Enhanced corticosterone levels can promote survival of stressful events; however, in situations where a stressor persists and corticosterone levels remain elevated, the adrenocortical response can be detrimental. A potential ecological stressor for wild birds is parasitism by ectoparasites. We studied the stress response of 11-23-day-old brown pelican (Pelecanus occidentalis) nestlings by measuring plasma corticosterone levels in relation to the presence of the soft tick Carios capensis at two colonies in South Carolina in 2005. We expected to see higher baseline and stress-induced levels of corticosterone for parasitized chicks compared to those nestlings with no ticks. Although nestlings mounted a response to capture stress, tick category was not associated with corticosterone levels at either colony. Our results appear to contrast those of previous studies and indicate that the adrenocortical response of the host is likely dependent on the type of ectoparasite and the degree of infestation. ?? 2009 Elsevier Inc.

The Role of Grain Size on Neutron Irradiation Response of Nanocrystalline Copper

PubMed Central

Mohamed, Walid; Miller, Brandon; Porter, Douglas; Murty, Korukonda

2016-01-01

The role of grain size on the developed microstructure and mechanical properties of neutron irradiated nanocrystalline copper was investigated by comparing the radiation response of material to the conventional micrograined counterpart. Nanocrystalline (nc) and micrograined (MG) copper samples were subjected to a range of neutron exposure levels from 0.0034 to 2 dpa. At all damage levels, the response of MG-copper was governed by radiation hardening manifested by an increase in strength with accompanying ductility loss. Conversely, the response of nc-copper to neutron irradiation exhibited a dependence on the damage level. At low damage levels, grain growth was the primary response, with radiation hardening and embrittlement becoming the dominant responses with increasing damage levels. Annealing experiments revealed that grain growth in nc-copper is composed of both thermally-activated and irradiation-induced components. Tensile tests revealed minimal change in the source hardening component of the yield stress in MG-copper, while the source hardening component was found to decrease with increasing radiation exposure in nc-copper. PMID:28773270

Subpopulations of M-MDSCs from mice infected by an immunodeficiency-causing retrovirus and their differential suppression of T- vs B-cell responses.

PubMed

O'Connor, Megan A; Fu, Whitney W; Green, Kathy A; Green, William R

2015-11-01

Monocytic (CD11b(+)Ly6G(±/Lo)Ly6C(+)) myeloid derived suppressor cells (M-MDSCs) expand following murine retroviral LP-BM5 infection and suppress ex vivo polyclonal T-cell and B-cell responses. M-MDSCs 3 weeks post LP-BM5 infection have decreased suppression of T-cell, but not B-cell, responses and alterations in the degree of iNOS/NO dependence of suppression. M-MDSCs from LP-BM5 infected mice were sorted into four quadrant populations (Ly6C/CD11b density): all quadrants suppressed B-cell responses, but only M-MDSCs expressing the highest levels of Ly6C and CD11b (Q2) significantly suppressed T-cell responses. Further subdivision of this Q2 population revealed the Ly6C(+/Hi) M-MDSC subpopulation as the most suppressive, inhibiting T- and B-cell responses in a full, or partially, iNOS/NO-dependent manner, respectively. In contrast, the lower/moderate levels of suppression by the Ly6C(+/Lo) and Ly6C(+/Mid) M-MDSC Q2 subpopulations, whether versus T- and/or B-cells, displayed little/no iNOS dependency for suppression. These results highlight differential phenotypic and functional immunosuppressive M-MDSC subsets in a retroviral immunodeficiency model. Published by Elsevier Inc.

Rapid effects of aldosterone in primary cultures of cardiomyocytes - do they suggest the existence of a membrane-bound receptor?

PubMed

Araujo, Carolina Morais; Hermidorff, Milla Marques; Amancio, Gabriela de Cassia Sousa; Lemos, Denise da Silveira; Silva, Marcelo Estáquio; de Assis, Leonardo Vinícius Monteiro; Isoldi, Mauro César

2016-10-01

Aldosterone acts on its target tissue through a classical mechanism or through the rapid pathway through a putative membrane-bound receptor. Our goal here was to better understand the molecular and biochemical rapid mechanisms responsible for aldosterone-induced cardiomyocyte hypertrophy. We have evaluated the hypertrophic process through the levels of ANP, which was confirmed by the analysis of the superficial area of cardiomyocytes. Aldosterone increased the levels of ANP and the cellular area of the cardiomyocytes; spironolactone reduced the aldosterone-increased ANP level and cellular area of cardiomyocytes. Aldosterone or spironolactone alone did not increase the level of cyclic 3',5'-adenosine monophosphate (cAMP), but aldosterone plus spironolactone led to increased cAMP level; the treatment with aldosterone + spironolactone + BAPTA-AM reduced the levels of cAMP. These data suggest that aldosterone-induced cAMP increase is independent of mineralocorticoid receptor (MR) and dependent on Ca(2+). Next, we have evaluated the role of A-kinase anchor proteins (AKAP) in the aldosterone-induced hypertrophic response. We have found that St-Ht31 (AKAP inhibitor) reduced the increased level of ANP which was induced by aldosterone; in addition, we have found an increase on protein kinase C (PKC) and extracellular signal-regulated kinase 5 (ERK5) activity when cells were treated with aldosterone alone, spironolactone alone and with a combination of both. Our data suggest that PKC could be responsible for ERK5 aldosterone-induced phosphorylation. Our study suggests that the aldosterone through its rapid effects promotes a hypertrophic response in cardiomyocytes that is controlled by an AKAP, being dependent on ERK5 and PKC, but not on cAMP/cAMP-dependent protein kinase signaling pathways. Lastly, we provide evidence that the targeting of AKAPs could be relevant in patients with aldosterone-induced cardiac hypertrophy and heart failure.

Influence of music training on academic examination-induced stress in Thai adolescents.

PubMed

Laohawattanakun, Janejira; Chearskul, Supornpim; Dumrongphol, Hattaya; Jutapakdeegul, Nuanchan; Yensukjai, Juntima; Khumphan, Nipaporn; Niltiean, Songwit; Thangnipon, Wipawan

2011-01-10

Several pieces of evidence suggest that academic examinations fulfill the classical requirement of a psychological stressor. Academic examinations represent a stressful challenge to many students, but studies on examination-dependent corticosteroid response, a sensitive physiological indicator of a stress response, are inconsistent. In addition, several studies showed that music can decrease cortisol and adrenocorticotropic hormone (ACTH) levels, and other studies have found that music also may enhance a variety of cognitive functions, such as attention, learning, communication and memory. The present study investigated cortisol response in saliva of Thai adolescents taking academic examinations and analyzed the differences of the stress response between musician and control subjects. Also, we observed whether the academic examination-dependent corticosteroid response affected learning and memory in the test subjects, which comprised 30 musician and 30 control students, age ranging from 15 to 17 years. Mathematical examinations were used as the stressor. Pre- and post-academic examination saliva cortisol levels were measured including self-estimated stress levels. Results showed that the pre-academic examination saliva cortisol concentrations of the musician group are significantly lower than those of the control group, whereas there is no difference in the stress inventory scores. Interestingly, among students with grade point average (GPA) of >3.50, pre-academic examination cortisol levels are significantly lower in the musician compared with control group. This study suggests that under academic examination-induced stress condition, music training can reduce saliva cortisol level in Thai adolescents. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

THE EFFECTS OF RESPONSE EFFORT ON SAFE PERFORMANCE BY THERAPISTS AT AN AUTISM TREATMENT FACILITY

PubMed Central

Casella, Sarah E; Wilder, David A; Neidert, Pamela; Rey, Catalina; Compton, Megan; Chong, Ivy

2010-01-01

The effects of response effort on safe behaviors (i.e., glove wearing, hand sanitizing, and electrical outlet replacement) exhibited by therapists at an autism treatment center were examined. Participants were exposed to 2 or 3 levels of effort (i.e., high, medium, low) for each dependent variable. Results showed increased safe performance during the low-effort conditions relative to other conditions across all dependent variables for all participants. PMID:21541157

Dose-response relationships for the onset of avoidance of sonar by free-ranging killer whales.

PubMed

Miller, Patrick J O; Antunes, Ricardo N; Wensveen, Paul J; Samarra, Filipa I P; Alves, Ana Catarina; Tyack, Peter L; Kvadsheim, Petter H; Kleivane, Lars; Lam, Frans-Peter A; Ainslie, Michael A; Thomas, Len

2014-02-01

Eight experimentally controlled exposures to 1-2 kHz or 6-7 kHz sonar signals were conducted with four killer whale groups. The source level and proximity of the source were increased during each exposure in order to reveal response thresholds. Detailed inspection of movements during each exposure session revealed sustained changes in speed and travel direction judged to be avoidance responses during six of eight sessions. Following methods developed for Phase-I clinical trials in human medicine, response thresholds ranging from 94 to 164 dB re 1 μPa received sound pressure level (SPL) were fitted to Bayesian dose-response functions. Thresholds did not consistently differ by sonar frequency or whether a group had previously been exposed, with a mean SPL response threshold of 142 ± 15 dB (mean ± s.d.). High levels of between- and within-individual variability were identified, indicating that thresholds depended upon other undefined contextual variables. The dose-response functions indicate that some killer whales started to avoid sonar at received SPL below thresholds assumed by the U.S. Navy. The predicted extent of habitat over which avoidance reactions occur depends upon whether whales responded to proximity or received SPL of the sonar or both, but was large enough to raise concerns about biological consequences to the whales.

Drivers for the Value of Demand Response under Increased Levels of Wind and Solar Power; NREL (National Renewable Energy Laboratory)

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

Hale, Elaine

Demand response may be a valuable flexible resource for low-carbon electric power grids. However, there are as many types of possible demand response as there are ways to use electricity, making demand response difficult to study at scale in realistic settings. This talk reviews our state of knowledge regarding the potential value of demand response in several example systems as a function of increasing levels of wind and solar power, sometimes drawing on the analogy between demand response and storage. Overall, we find demand response to be promising, but its potential value is very system dependent. Furthermore, demand response, likemore » storage, can easily saturate ancillary service markets.« less

Monaural and binaural contributions to interaural-level-difference sensitivity in human auditory cortex.

PubMed

Stecker, G Christopher; McLaughlin, Susan A; Higgins, Nathan C

2015-10-15

Whole-brain functional magnetic resonance imaging was used to measure blood-oxygenation-level-dependent (BOLD) responses in human auditory cortex (AC) to sounds with intensity varying independently in the left and right ears. Echoplanar images were acquired at 3 Tesla with sparse image acquisition once per 12-second block of sound stimulation. Combinations of binaural intensity and stimulus presentation rate were varied between blocks, and selected to allow measurement of response-intensity functions in three configurations: monaural 55-85 dB SPL, binaural 55-85 dB SPL with intensity equal in both ears, and binaural with average binaural level of 70 dB SPL and interaural level differences (ILD) ranging ±30 dB (i.e., favoring the left or right ear). Comparison of response functions equated for contralateral intensity revealed that BOLD-response magnitudes (1) generally increased with contralateral intensity, consistent with positive drive of the BOLD response by the contralateral ear, (2) were larger for contralateral monaural stimulation than for binaural stimulation, consistent with negative effects (e.g., inhibition) of ipsilateral input, which were strongest in the left hemisphere, and (3) also increased with ipsilateral intensity when contralateral input was weak, consistent with additional, positive, effects of ipsilateral stimulation. Hemispheric asymmetries in the spatial extent and overall magnitude of BOLD responses were generally consistent with previous studies demonstrating greater bilaterality of responses in the right hemisphere and stricter contralaterality in the left hemisphere. Finally, comparison of responses to fast (40/s) and slow (5/s) stimulus presentation rates revealed significant rate-dependent adaptation of the BOLD response that varied across ILD values. Copyright © 2015. Published by Elsevier Inc.

Cortistatin Is a Key Factor Regulating the Sex-Dependent Response of the GH and Stress Axes to Fasting in Mice.

PubMed

Cordoba-Chacón, José; Gahete, Manuel D; Pozo-Salas, Ana I; de Lecea, Luis; Castaño, Justo P; Luque, Raúl M

2016-07-01

Cortistatin (CORT) shares high structural and functional similarities with somatostatin (SST) but displays unique sex-dependent pituitary actions. Indeed, although female CORT-knockout (CORT-KO) mice exhibit enhanced GH expression/secretion, Proopiomelanocortin expression, and circulating ACTH/corticosterone/ghrelin levels, male CORT-KO mice only display increased plasma GH/corticosterone levels. Changes in peripheral ghrelin and SST (rather than hypothalamic levels) seem to regulate GH/ACTH axes in CORT-KOs under fed conditions. Because changes in GH/ACTH axes during fasting provide important adaptive mechanisms, we sought to determine whether CORT absence influences GH/ACTH axes during fasting. Accordingly, fed and fasted male/female CORT-KO were compared with littermate controls. Fasting increased circulating GH levels in male/female controls but not in CORT-KO, suggesting that CORT can be a relevant regulator of GH secretion during fasting. However, GH levels were already higher in CORT-KO than in controls in fed state, which might preclude a further elevation in GH levels. Interestingly, although fasting-induced pituitary GH expression was elevated in both male/female controls, GH expression only increased in fasted female CORT-KOs, likely owing to specific changes observed in key factors controlling somatotrope responsiveness (ie, circulating ghrelin and IGF-1, and pituitary GHRH and ghrelin receptor expression). Fasting increased corticosterone levels in control and, most prominently, in CORT-KO mice, which might be associated with a desensitization to SST signaling and to an augmentation in CRH and ghrelin-signaling regulating corticotrope function. Altogether, these results provide compelling evidence that CORT plays a key, sex-dependent role in the regulation of the GH/ACTH axes in response to fasting.

Combinations of physiologic estrogens with xenoestrogens alter calcium and kinase responses, prolactin release, and membrane estrogen receptor trafficking in rat pituitary cells

PubMed Central

2010-01-01

Background Xenoestrogens such as alkylphenols and the structurally related plastic byproduct bisphenol A have recently been shown to act potently via nongenomic signaling pathways and the membrane version of estrogen receptor-α. Though the responses to these compounds are typically measured individually, they usually contaminate organisms that already have endogenous estrogens present. Therefore, we used quantitative medium-throughput screening assays to measure the effects of physiologic estrogens in combination with these xenoestrogens. Methods We studied the effects of low concentrations of endogenous estrogens (estradiol, estriol, and estrone) at 10 pM (representing pre-development levels), and 1 nM (representing higher cycle-dependent and pregnancy levels) in combinations with the same levels of xenoestrogens in GH3/B6/F10 pituitary cells. These levels of xenoestrogens represent extremely low contamination levels. We monitored calcium entry into cells using Fura-2 fluorescence imaging of single cells. Prolactin release was measured by radio-immunoassay. Extracellular-regulated kinase (1 and 2) phospho-activations and the levels of three estrogen receptors in the cell membrane (ERα, ERβ, and GPER) were measured using a quantitative plate immunoassay of fixed cells either permeabilized or nonpermeabilized (respectively). Results All xenoestrogens caused responses at these concentrations, and had disruptive effects on the actions of physiologic estrogens. Xenoestrogens reduced the % of cells that responded to estradiol via calcium channel opening. They also inhibited the activation (phosphorylation) of extracellular-regulated kinases at some concentrations. They either inhibited or enhanced rapid prolactin release, depending upon concentration. These latter two dose-responses were nonmonotonic, a characteristic of nongenomic estrogenic responses. Conclusions Responses mediated by endogenous estrogens representing different life stages are vulnerable to very low concentrations of these structurally related xenoestrogens. Because of their non-classical dose-responses, they must be studied in detail to pinpoint effective concentrations and the directions of response changes. PMID:20950447

Complicated Grief & Depression in Young Adults: Personality & Relationship Quality

PubMed Central

Herberman Mash, Holly B.; Fullerton, Carol S.; Shear, M. Katherine; Ursano, Robert J.

2014-01-01

Young adults experience problematic responses to loss more often than is commonly recognized. Few empirical studies have examined the contribution of intra- and interpersonal characteristics to grief and depression in bereaved young adults. This study investigated the association of dependency and quality of the relationship with the deceased (i.e., depth and conflict) with complicated grief (CG) and depression. Participants were 157 young adults aged 17–29 who experienced loss of a family member or close friend within the past three years (M = 1.74 years). Participants completed the Inventory of Complicated Grief, Beck Depression Inventory, Depth and Conflict subscales of the Quality of Relationships Inventory, and the Dependency subscale of the Depressive Experiences Questionnaire. Relationships among dependency and interpersonal depth and conflict and CG and depression were examined through analyses of covariance. Sixteen percent of participants met criteria for CG and 34% had mild to severe depression. Dependency and depth were independently related to CG and dependency was related to depression, but the pattern of associations was somewhat different for each outcome. Greater depth was associated with CG, at both high and low levels of dependency. High levels of dependency were related to more depressive symptoms. Interpretation of the findings is limited by the relatively small sample size and cross-sectional design. CG and depression are related but distinct responses to loss. Although dependency is associated with both CG and depression following loss, relationships between the bereaved and deceased that are characterized by high levels of depth are particularly related to the development of CG symptoms. PMID:24921421

Chronic alteration in phosphatidylinositol 4,5-bisphosphate levels regulates capsaicin and mustard oil responses

PubMed Central

Patil, Mayur J.; Belugin, Sergei; Akopian, Armen N.

2011-01-01

There is an agreement that acute (in minutes) hydrolysis and accumulation of phosphatidylinositol 4,5-bisphosphate (PIP2) modulate TRPV1 and TRPA1 activities. Since inflammation results in PIP2 depletion, persisting for long periods (hours-to-days) in pain models and in clinic, we examined whether chronic depletion and accumulation of PIP2 affects capsaicin and mustard oil responses. In addition we also wanted to evaluate whether the effects of PIP2 depend on TRPV1 and TRPA1 co-expression, and whether the PIP2 actions vary in expression cells versus sensory neurons. Chronic PIP2 production was stimulated by over-expression of phosphatidylinositol-4-phosphate-5-kinase, while PIP2-specific phospholipid 5′-phosphatase was selected to reduce plasma membrane levels of PIP2. Our results demonstrate that capsaicin (100 nM; CAP) responses and receptor tachyphylaxis are not significantly influenced by chronic changes in PIP2 levels in wild-type (WT) or TRPA1 null-mutant sensory neurons, as well as CHO cells expressing TRPV1 alone or with TRPA1. However, low concentrations of CAP (20 nM) produced a higher response after PIP2 depletion in cells containing TRPV1 alone, but not TRPV1 together with TRPA1. Mustard oil (25 μM; MO) responses were also not affected by PIP2 in WT sensory neurons and cells co-expressing TRPA1 and TRPV1. In contrast, PIP2 reduction leads to pronounced tachyphylaxis to MO in cells with both channels. Chronic effect of PIP2 on TRPA1 activity depends on presence of the TRPV1 channel and cell type (CHO vs. sensory neurons). In summary, chronic alterations in PIP2 levels regulate magnitude of CAP and MO responses, as well as MO-tachyphylaxis. This regulation depends on co-expression profile of TRPA1 and TRPV1 and cell type. PMID:21337373

Chronic alteration in phosphatidylinositol 4,5-biphosphate levels regulates capsaicin and mustard oil responses.

PubMed

Patil, Mayur J; Belugin, Sergei; Akopian, Armen N

2011-06-01

There is an agreement that acute (in minutes) hydrolysis and accumulation of phosphatidylinositol 4,5-bisphosphate (PIP(2) ) modulate TRPV1 and TRPA1 activities. Because inflammation results in PIP(2) depletion, persisting for long periods (hours to days) in pain models and in the clinic, we examined whether chronic depletion and accumulation of PIP(2) affect capsaicin (CAP) and mustard oil (MO) responses. In addition, we wanted to evaluate whether the effects of PIP(2) depend on TRPV1 and TRPA1 coexpression and whether the PIP(2) actions vary in expression cells vs. sensory neurons. Chronic PIP(2) production was stimulated by overexpression of phosphatidylinositol-4-phosphate-5-kinase, and PIP(2) -specific phospholipid 5'-phosphatase was selected to reduce plasma membrane levels of PIP(2) . Our results demonstrate that CAP (100 nM) responses and receptor tachyphylaxis are not significantly influenced by chronic changes in PIP(2) levels in wild-type (WT) or TRPA1 null-mutant sensory neurons as well as CHO cells expressing TRPV1 alone or with TRPA1. However, low concentrations of CAP (20 nM) produced a higher response after PIP(2) depletion in cells containing TRPV1 alone but not TRPV1 together with TRPA1. MO (25 μM) responses were also not affected by PIP(2) in WT sensory neurons and cells coexpressing TRPA1 and TRPV1. In contrast, PIP(2) reduction leads to pronounced tachyphylaxis to MO in cells with both channels. Chronic effect of PIP(2) on TRPA1 activity depends on presence of the TRPV1 channel and cell type (CHO vs. sensory neurons). In summary, chronic alterations in PIP(2) levels regulate magnitude of CAP and MO responses as well as MO tachyphylaxis. This regulation depends on coexpression profile of TRPA1 and TRPV1 and cell type. Copyright © 2011 Wiley-Liss, Inc.

2',5'-Dihydroxychalcone-induced glutathione is mediated by oxidative stress and kinase signaling pathways.

PubMed

Kachadourian, Remy; Pugazhenthi, Subbiah; Velmurugan, Kalpana; Backos, Donald S; Franklin, Christopher C; McCord, Joe M; Day, Brian J

2011-09-15

Hydroxychalcones are naturally occurring compounds that continue to attract considerable interest because of their anti-inflammatory and antiangiogenic properties. They have been reported to inhibit the synthesis of the inducible nitric oxide synthase and to induce the expression of heme oxygenase-1. This study examines the mechanisms by which 2',5'-dihydroxychalcone (2',5'-DHC) induces an increase in cellular glutathione (GSH) levels using a cell line stably expressing a luciferase reporter gene driven by antioxidant-response elements (MCF-7/AREc32). The 2',5'-DHC-induced increase in cellular GSH levels was partially inhibited by the catalytic antioxidant MnTDE-1,3-IP(5+), suggesting that reactive oxygen species (ROS) mediate the antioxidant adaptive response. 2',5'-DHC treatment induced phosphorylation of the c-Jun N-terminal kinase (JNK) pathway, which was also inhibited by MnTDE-1,3-IP(5+). These findings suggest a ROS-dependent activation of the AP-1 transcriptional response. However, whereas 2',5'-DHC triggered the NF-E2-related factor 2 (Nrf2) transcriptional response, cotreatment with MnTDE-1,3-IP(5+) did not decrease 2',5'-DHC-induced Nrf2/ARE activity, showing that this pathway is not dependent on ROS. Moreover, pharmacological inhibitors of mitogen-activated protein kinase (MAPK) pathways showed a role for JNK and p38MAPK in mediating the 2',5'-DHC-induced Nrf2 response. These findings suggest that the 2',5'-DHC-induced increase in GSH levels results from a combination of ROS-dependent and ROS-independent pathways. Copyright © 2011 Elsevier Inc. All rights reserved.

Student understanding of time dependence in quantum mechanics

NASA Astrophysics Data System (ADS)

Emigh, Paul J.; Passante, Gina; Shaffer, Peter S.

2015-12-01

[This paper is part of the Focused Collection on Upper Division Physics Courses.] The time evolution of quantum states is arguably one of the more difficult ideas in quantum mechanics. In this article, we report on results from an investigation of student understanding of this topic after lecture instruction. We demonstrate specific problems that students have in applying time dependence to quantum systems and in recognizing the key role of the energy eigenbasis in determining the time dependence of wave functions. Through analysis of student responses to a set of four interrelated tasks, we categorize some of the difficulties that underlie common errors. The conceptual and reasoning difficulties that have been identified are illustrated through student responses to four sets of questions administered at different points in a junior-level course on quantum mechanics. Evidence is also given that the problems persist throughout undergraduate instruction and into the graduate level.

ERK Oscillation-Dependent Gene Expression Patterns and Deregulation by Stress-Response

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

Waters, Katrina M.; Cummings, Brian S.; Shankaran, Harish

2014-09-15

Studies were undertaken to determine whether ERK oscillations regulate a unique subset of genes in human keratinocytes and subsequently, whether the p38 stress response inhibits ERK oscillations. A DNA microarray identified many genes that were unique to ERK oscillations, and network reconstruction predicted an important role for the mediator complex subunit 1 (MED1) node in mediating ERK oscillation-dependent gene expression. Increased ERK-dependent phosphorylation of MED1 was observed in oscillating cells compared to non-oscillating counterparts as validation. Treatment of keratinocytes with a p38 inhibitor (SB203580) increased ERK oscillation amplitudes and MED1 and phospho-MED1 protein levels. Bromate is a probable human carcinogenmore » that activates p38. Bromate inhibited ERK oscillations in human keratinocytes and JB6 cells and induced an increase in phospho-p38 and decrease in phospho-MED1 protein levels. Treatment of normal rat kidney cells and primary salivary gland epithelial cells with bromate decreased phospho-MED1 levels in a reversible fashion upon treatment with p38 inhibitors (SB202190; SB203580). Our results indicate that oscillatory behavior in the ERK pathway alters homeostatic gene regulation patterns and that the cellular response to perturbation may manifest differently in oscillating vs non-oscillating cells.« less

Predicting Long-term Temperature Increase for Time-Dependent SAR Levels with a Single Short-term Temperature Response

PubMed Central

Carluccio, Giuseppe; Bruno, Mary; Collins, Christopher M.

2015-01-01

Purpose Present a novel method for rapid prediction of temperature in vivo for a series of pulse sequences with differing levels and distributions of specific energy absorption rate (SAR). Methods After the temperature response to a brief period of heating is characterized, a rapid estimate of temperature during a series of periods at different heating levels is made using a linear heat equation and Impulse-Response (IR) concepts. Here the initial characterization and long-term prediction for a complete spine exam are made with the Pennes’ bioheat equation where, at first, core body temperature is allowed to increase and local perfusion is not. Then corrections through time allowing variation in local perfusion are introduced. Results The fast IR-based method predicted maximum temperature increase within 1% of that with a full finite difference simulation, but required less than 3.5% of the computation time. Even higher accelerations are possible depending on the time step size chosen, with loss in temporal resolution. Correction for temperature-dependent perfusion requires negligible additional time, and can be adjusted to be more or less conservative than the corresponding finite difference simulation. Conclusion With appropriate methods, it is possible to rapidly predict temperature increase throughout the body for actual MR examinations. (200/200 words) PMID:26096947

Predicting long-term temperature increase for time-dependent SAR levels with a single short-term temperature response.

PubMed

Carluccio, Giuseppe; Bruno, Mary; Collins, Christopher M

2016-05-01

Present a novel method for rapid prediction of temperature in vivo for a series of pulse sequences with differing levels and distributions of specific energy absorption rate (SAR). After the temperature response to a brief period of heating is characterized, a rapid estimate of temperature during a series of periods at different heating levels is made using a linear heat equation and impulse-response (IR) concepts. Here the initial characterization and long-term prediction for a complete spine exam are made with the Pennes' bioheat equation where, at first, core body temperature is allowed to increase and local perfusion is not. Then corrections through time allowing variation in local perfusion are introduced. The fast IR-based method predicted maximum temperature increase within 1% of that with a full finite difference simulation, but required less than 3.5% of the computation time. Even higher accelerations are possible depending on the time step size chosen, with loss in temporal resolution. Correction for temperature-dependent perfusion requires negligible additional time and can be adjusted to be more or less conservative than the corresponding finite difference simulation. With appropriate methods, it is possible to rapidly predict temperature increase throughout the body for actual MR examinations. © 2015 Wiley Periodicals, Inc.

Modeling Nonignorable Missing Data in Speeded Tests

ERIC Educational Resources Information Center

Glas, Cees A. W.; Pimentel, Jonald L.

2008-01-01

In tests with time limits, items at the end are often not reached. Usually, the pattern of missing responses depends on the ability level of the respondents; therefore, missing data are not ignorable in statistical inference. This study models data using a combination of two item response theory (IRT) models: one for the observed response data and…

Distinct effects of thrombopoietin depending on a threshold level of activated Mpl in BaF-3 cells.

PubMed

Millot, Gaël A; Vainchenker, William; Duménil, Dominique; Svinarchuk, Fédor

2002-06-01

Thrombopoietin (TPO) plays a critical role in megakaryopoiesis through binding to its receptor Mpl. This involves activation of various intracellular signaling pathways, including phosphoinositide 3-kinase (PI3K) and the mitogen-activated protein kinase (MAPK) pathways. Their precise role in TPO-mediated proliferation, survival and differentiation is not fully understood. In the present study, we show that TPO induces different biological responses in Mpl-transduced BaF-3 cells, depending on the cell surface density of Mpl and the resulting activation level of signaling pathways. TPO mediates cell proliferation in cells expressing high levels of Mpl but only mediates survival without proliferation in cells expressing low levels of the receptor. By using the kinase inhibitors PD98059 and LY294002, we further showed that the activation level of the PI3K and MAPK p42/44 pathways is a determining factor for the proliferative effect. In cells expressing low levels of Mpl, the survival effect was strongly dependent on the activation level of the PI3K/AKT, but not the MAPK p42/44 pathway. Moreover, this effect was correlated with the phosphorylation level of BAD but not with the expression level of Bcl-X(L). However, PI3K pathway inhibition did not increase apoptosis when BaF-3 cells proliferated in response to TPO, indicating a compensating mechanism from other Mpl signaling pathways in this case.

Second-line tests in the differential diagnosis of ACTH-dependent Cushing's syndrome.

PubMed

Barbot, Mattia; Trementino, Laura; Zilio, Marialuisa; Ceccato, Filippo; Albiger, Nora; Daniele, Andrea; Frigo, Anna Chiara; Mardari, Rodica; Rolma, Giuseppe; Boscaro, Marco; Arnaldi, Giorgio; Scaroni, Carla

2016-10-01

Diagnosing Cushing's syndrome (CS) can be a challenge, especially in ACTH-dependent CS, when it comes to detecting the origin of ACTH secretion. Retrospective data were collected on 170 patients with ACTH-dependent CS (149 CD, 21 EAS) referring to two endocrinology units, focusing on three non-invasive tests: dexamethasone 8 mg overnight challenge (HDDST); corticotrophin-releasing hormone (CRH) assay and the desmopressin (DDAVP) test. Patients with EAS were slightly older and had higher ACTH, serum and urinary cortisol levels than patients with CD (p < 0.01). CD patients had a stronger ACTH and cortisol response after CRH injection (p < 0.0001), and a more pronounced reduction in cortisol levels after HDDST (p < 0.0001). A threshold percentage ACTH increase after CRH stimulation of 72.4 % was able to identify CD with a sensitivity (SE) of 76 % (95 % CI 68-83) and a specificity (SP) of 100 % (95 % CI 83-100). As for HDDST, a cortisol suppression >52.7 % below the basal level suggested a pituitary origin with a SE of 88 % (95 % CI 81-93) and a SP of 90 % (95 % CI 68-99). There were no cases of EAS with positive responses to both these tests. Increases in ACTH and cortisol levels after the DDAVP test were also higher in CD than in EAS (p < 0.01), though the SE and SP were lower. Patients with CD showed a stronger response to HDDST and CRH, and the adopted cut-offs showed a good SE and SP in discriminating them from patients with EAS. Concordant tests indicated CD when positive, whereas no response to either test was highly suggestive of EAS. The DDAVP test was of limited utility in the diagnostic phase. In conclusion, the choice of tests may play an important part in the differential diagnosis of ACTH-dependent CS.

Integration of Density Dependence and Concentration Response Models Provides an Ecologically Relevant Assessment of Populations Exposed to Toxicants

EPA Science Inventory

The assessment of toxic exposure on wildlife populations involves the integration of organism level effects measured in toxicity tests (e.g., chronic life cycle) and population models. These modeling exercises typically ignore density dependence, primarily because information on ...

Leptin, immune responses and autoimmune disease. Perspectives on the use of leptin antagonists.

PubMed

Peelman, F; Iserentant, H; Eyckerman, S; Zabeau, L; Tavernier, J

2005-01-01

The pivotal role of leptin in regulating body weight and energy homeostasis is very well established. More recently, leptin also emerged as an important regulator of T-cell-dependent immunity. Reduced leptin levels, as observed during periods of starvation, correlate with an impaired cellular immune response, whereby especially the T(H)1 pro-inflammatory immune response appears to be affected. Physiologically, this could reflect the high energy demand of such processes, which are suppressed in animals or people with nutrient shortage. Several autoimmune diseases are T(H)1 T-cell dependent. In line with a pro-inflammatory role for leptin, animal models of leptin deficiency are markedly resistant to a variety of T-cell dependent autoimmune diseases. Here, we review the role of leptin in immune responses, with emphasis on autoimmune diseases. The design and potential use of leptin antagonists is also discussed.

Integration of supercapacitive storage in renewable energy system to compare the response of two level and five level inverter with RL type load

NASA Astrophysics Data System (ADS)

Jana, Suman; Biswas, Pabitra Kumar; Das, Upama

2018-04-01

The analytical and simulation-based study in this presented paper shows a comparative report between two level inverter and five-level inverter with the integration of Supercapacitive storage in Renewable Energy system. Sometime dependent numerical models are used to measure the voltage and current response of two level and five level inverter in MATLAB Simulink based environment. In this study supercapacitive sources, which are fed by solar cells are used as input sources to experiment the response of multilevel inverter with integration of su-percapacitor as a storage device of Renewable Energy System. The RL load is used to compute the time response in MATLABSimulink based environment. With the simulation results a comparative study has been made of two different level types of inverters. Two basic types of inverter are discussed in the study with reference to their electrical behavior. It is also simulated that multilevel inverter can convert stored energy within supercapacitor which is extracted from Renewable Energy System.

Level-dependent coronal and axial moment-rotation corridors of degeneration-free cervical spines in lateral flexion.

PubMed

Yoganandan, Narayan; Pintar, Frank A; Stemper, Brian D; Wolfla, Christopher E; Shender, Barry S; Paskoff, Glenn

2007-05-01

Aging, trauma, or degeneration can affect intervertebral kinematics. While in vivo studies can determine motions, moments are not easily quantified. Previous in vitro studies on the cervical spine have largely used specimens from older individuals with varying levels of degeneration and have shown that moment-rotation responses under lateral bending do not vary significantly by spinal level. The objective of the present in vitro biomechanical study was, therefore, to determine the coronal and axial moment-rotation responses of degeneration-free, normal, intact human cadaveric cervicothoracic spinal columns under the lateral bending mode. Nine human cadaveric cervical columns from C2 to T1 were fixed at both ends. The donors had ranged from twenty-three to forty-four years old (mean, thirty-four years) at the time of death. Retroreflective targets were inserted into each vertebra to obtain rotational kinematics in the coronal and axial planes. The specimens were subjected to pure lateral bending moment with use of established techniques. The range-of-motion and neutral zone metrics for the coronal and axial rotation components were determined at each level of the spinal column and were evaluated statistically. Statistical analysis indicated that the two metrics were level-dependent (p < 0.05). Coronal motions were significantly greater (p < 0.05) than axial motions. Moment-rotation responses were nonlinear for both coronal and axial rotation components under lateral bending moments. Each segmental curve for both rotation components was well represented by a logarithmic function (R(2) > 0.95). Range-of-motion metrics compared favorably with those of in vivo investigations. Coronal and axial motions of degeneration-free cervical spinal columns under lateral bending showed substantially different level-dependent responses. The presentation of moment-rotation corridors for both metrics forms a normative dataset for the degeneration-free cervical spines.

Appetite, Glycemia, and Entero-Insular Hormone Responses Differ Between Oral, Gastric-Remnant, and Duodenal Administration of a Mixed-Meal Test After Roux-en-Y Gastric Bypass.

PubMed

Gero, Daniel; Steinert, Robert E; Hosa, Hanna; Cummings, David E; Bueter, Marco

2018-06-01

To examine the effect of different feeding routes on appetite and metabolic responses after Roux-en-Y gastric bypass (RYGB). A standard liquid meal was administered either orally, into the gastric remnant, or intraduodenally 6 months after RYGB. Changes in plasma glucose, insulin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY), and appetite were measured pre- and postprandially. Postprandial GLP-1 and PYY responses were similar, whereas glucose, insulin, and GIP levels differed markedly after oral versus intraduodenal feeding. Intraduodenal feeding prompted an intermediate appetite response (i.e., between oral and intragastric). For postprandial glucose, insulin, and GIP levels, the intraduodenal route was more similar to the intragastric than the oral route. Intragastric administration did not evoke changes in appetite, glucose, or insulin; however, it slightly increased GLP-1 and PYY and moderately increased GIP. Appetite and metabolic responses after RYGB depend on the route by which nutrients enter the gastrointestinal tract. © 2018 by the American Diabetes Association.

Defects in codoped NiO with gigantic dielectric response

NASA Astrophysics Data System (ADS)

Wu, Ping; Ligatchev, Valeri; Yu, Zhi Gen; Zheng, Jianwei; Sullivan, Michael B.; Zeng, Yingzhi

2009-06-01

We combine first-principles, statistical, and phenomenological methods to investigate the electronic and dielectric properties of NiO and clarify the nature of the gigantic dielectric response in codoped NiO. Unlike previous models which are dependent on grain-boundary effects, our model based on small polaron hopping in homogeneous material predicts the dielectric permittivity (104-5) for heavily Li- and MD -codoped NiO (MD=Ti,Al,Si) . Furthermore, we reproduce the experimental trends in dielectric properties as a function of the dopants nature and their concentrations, as well as the reported activation energies for the relaxation in Li- and Ti-codoped NiO (0.308 eV or 0.153 eV depending on the Fermi-level position). In this study, we demonstrate that small polaron hopping on dopant levels is the dominant mechanism for the gigantic dielectric response in these codoped NiO.

Combined effects of physiological condition and environmental attributes in determining call plasticity.

PubMed

Ziegler, Lucia; Arim, Matias; Bozinovic, Francisco

2018-05-07

Evidence is growing on the ability of anurans to make immediate call adjustments in response to the propagation properties of the environment. However, our understanding of such flexibility is typically based on dichotomous stimuli (i.e. presence/absence), while its condition-dependence has been little explored. We experimentally studied the ability of adjustment and its condition dependence of advertisement calls of Hypsiboas pulchellus in response to different levels of attenuation. Individuals modified most call parameters analyzed, although the direction of adjustments was contingent on individual identity, level of attenuation and trait category (i.e. spectral or temporal). Under low attenuation conditions males lengthened some call elements, partially supporting the hypothesis of plasticity oriented towards maintaining signal transmission, but this trend was not present in the high attenuation treatment. Also, under both attenuation treatments males gave higher frequency notes, as expected from an energy-saving response to changes in social environment or reducing attractiveness due to risk perception. Across treatments individuals in better condition tended to exhibit higher plasticity. These results indicate that call structure could depend on the integration of different cues such as habitat propagation characteristics, acoustic competition for females, and predation risk, while the ability to behave flexibly depends on current body reserves. Copyright © 2018 Elsevier B.V. All rights reserved.

Association between insulin and executive functioning in alcohol dependence: a pilot study.

PubMed

Han, Changwoo; Bae, Hwallip; Won, Sung-Doo; Lim, Jaeyoung; Kim, Dai-Jin

2015-01-01

Alcohol dependence is a disorder ascribable to multiple factors and leads to cognitive impairment. Given that insulin dysregulation can cause cognitive impairment, patients with alcohol dependence are likely to develop insulin dysregulation such as that in diabetes. The purposes of this study are to identify an association between cognitive functioning and insulin and to investigate insulin as the biomarker of cognitive functioning in alcohol-dependent patients. Serum insulin levels were measured and cognitive functions were assessed in 45 patients with chronic alcoholism. The Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K), a battery of cognitive function tests, was used to assess cognitive functioning. Serum insulin levels were not significantly correlated with most CERAD-K scores, but there was a significant negative correlation with scores on the Trail Making Test B, which is designed to measure executive functioning. Lower serum insulin levels were associated with slower executive functioning responses on the Trail Making Test B, suggesting that executive functioning may be in proportion to serum insulin levels. Thus, in patients with alcohol dependence, insulin level is associated with cognitive functioning. In addition, the present findings suggest that insulin level is a potential biomarker for determining cognitive functioning.

Differential involvement of 3', 5'-cyclic adenosine monophosphate-dependent protein kinase in regulation of Fos and tyrosine hydroxylase expression in the heart after naloxone induced morphine withdrawal.

PubMed

Almela, Pilar; Cerezo, Manuela; González-Cuello, A; Milanés, M Victoria; Laorden, M Luisa

2007-01-01

We previously demonstrated that morphine withdrawal induced hyperactivity of the heart by the activation of noradrenergic pathways innervating the left and right ventricle, as evaluated by noradrenaline (NA) turnover and Fos expression. We investigated whether cAMP-dependent protein kinase (PKA) plays a role in this process by estimating changes in PKA immunoreactivity and the influence of inhibitor of PKA on Fos protein expression, tyrosine hydroxylase (TH) immunoreactivity levels and NA turnover in the left and right ventricle. Dependence on morphine was induced by a 7-day s.c. implantation of morphine pellets. Morphine withdrawal was precipitated on day 8 by an injection of naloxone (5 mg/kg). When opioid withdrawal was precipitated, an increase in PKA immunoreactivity and phospho-CREB (cyclic AMP response element protein) levels were observed in the heart. Moreover, morphine withdrawal induces Fos expression, an enhancement of NA turnover and an increase in the total TH levels. When the selective PKA inhibitor HA-1004 was infused, concomitantly with morphine pellets, it diminished the increase in NA turnover and the total TH levels observed in morphine-withdrawn rats. However, this inhibitor neither modifies the morphine withdrawal induced Fos expression nor the increase of nonphosphorylated TH levels. The present findings indicate that an up-regulated PKA-dependent transduction pathway might contribute to the activation of the cardiac catecholaminergic neurons in response to morphine withdrawal and suggest that Fos is not a target of PKA at heart levels.

Transcriptional dynamics with time-dependent reaction rates

NASA Astrophysics Data System (ADS)

Nandi, Shubhendu; Ghosh, Anandamohan

2015-02-01

Transcription is the first step in the process of gene regulation that controls cell response to varying environmental conditions. Transcription is a stochastic process, involving synthesis and degradation of mRNAs, that can be modeled as a birth-death process. We consider a generic stochastic model, where the fluctuating environment is encoded in the time-dependent reaction rates. We obtain an exact analytical expression for the mRNA probability distribution and are able to analyze the response for arbitrary time-dependent protocols. Our analytical results and stochastic simulations confirm that the transcriptional machinery primarily act as a low-pass filter. We also show that depending on the system parameters, the mRNA levels in a cell population can show synchronous/asynchronous fluctuations and can deviate from Poisson statistics.

Responsiveness of the Care Dependency Scale for Rehabilitation (CDS-R).

PubMed

Eichhorn-Kissel, Juliane; Dassen, Theo; Lohrmann, Christa

2012-03-01

Around 10% of Western Europe's population suffer from a disability which can entail a decrease of independency and quality of life. However, the lives of these people can be improved by rehabilitative treatment and care. Changing the degree of dependency from dependent to independent is essential in rehabilitation, as is the assessment of these changes. To perform such kind of measurements, assessment instruments have to be responsive. In spite of this concern, responsiveness of assessment instruments is studied to a small extent only. This also applies to the Care Dependency Scale for Rehabilitation (CDS-R), a short assessment instrument measuring the care dependency of patients regarding physical and psychosocial aspects. In this longitudinal-study, the responsiveness of the CDS-R, in general and related to different disease-groups, should be determined. Therefore, a convenience sample of 1564 patients was assessed in an Austrian rehabilitation centre with the scale after admission and before discharge. Responsiveness was determined by descriptive analysis, calculation of effect-sizes and significance tests. Differences between admission and discharge occurred on a statistically significant level for patients who changed. Kazis' effect-sizes can be considered as of small/medium effect for patients who changed (0.24/0.49), and as of large effect according to Liang (0.86/1.46). Eta squared was 0.10/0.19 which can be interpreted as of moderate/large effect for patients who changed. Responsiveness-analyses related to different disease-groups showed constantly large effect-sizes for patients with musculoskeletal-disorders. These results indicate that the CDS-R can detect patient-changes over time and discriminate between patients who change under rehabilitation or not. These aspects argue for the responsiveness of the scale, wherefore the CDS-R seems to be appropriate for the assessment of treatment/health-care effectiveness and the evaluation of individual patient-changes. Nevertheless further research is recommended to confirm the level of responsiveness of the scale in general and for different disease-groups. © 2011 The Authors. Scandinavian Journal of Caring Sciences © 2011 Nordic College of Caring Science.

An Item Response Theory Analysis of DSM-IV Cannabis Abuse and Dependence Criteria in Adolescents

PubMed Central

Hartman, Christie A.; Gelhorn, Heather; Crowley, Thomas J.; Sakai, Joseph T.; Stallings, Michael; Young, Susan E.; Rhee, Soo Hyun; Corley, Robin; Hewitt, John K.; Hopfer, Christian J.

2008-01-01

Objective To examine three aspects of adolescent cannabis problems: 1) do DSM-IV cannabis abuse and dependence criteria represent two different levels of severity of substance involvement, 2) to what degree do each of the 11 abuse and dependence criteria assess adolescent cannabis problems, and 3) do the DSM-IV items function similarly across different adolescent populations? Method We examined 5587 adolescents aged 11–19, including 615 youth in treatment for substance use disorders, 179 adjudicated youth, and 4793 youth from the community. All subjects were assessed with a structured diagnostic interview. Item response theory was utilized to analyze symptom endorsement patterns. Results Abuse and dependence criteria were not found to represent different levels of severity of problem cannabis use in any of the samples. Among the 11 abuse and dependence criteria, Problems cutting down and Legal problems were the least informative for distinguishing problem users. Two dependence criteria and three of the four abuse criteria indicated different severities of cannabis problems across samples. Conclusions We found little evidence to support the idea that abuse and dependence are separate constructs for adolescent cannabis problems. Furthermore, certain abuse criteria may indicate severe substance problems while specific dependence items may indicate less severe problems. The abuse items in particular need further study. These results have implications for the refinement of the current substance use disorder criteria for DSM-V. PMID:18176333

SHP-2 expression negatively regulates NK cell function1,2

PubMed Central

Purdy, Amanda K.; Campbell, Kerry S.

2009-01-01

Src homology region 2-containing protein tyrosine phosphatase-2 (SHP-2)4 is required for full activation of Ras/ERK in many cytokine and growth factor receptor signaling pathways. In contrast, SHP-2 inhibits activation of human natural killer (NK) cells upon recruitment to killer cell Ig-like receptors (KIR)4. To determine how SHP-2 impacts NK cell activation in KIR-dependent or KIR-independent signaling pathways, we employed knockdown and overexpression strategies in NK-like cell lines and analyzed the consequences on functional responses. In response to stimulation with susceptible target cells, SHP-2-silenced NK cells had elevated cytolytic activity and IFN-γ production, whereas cells overexpressing wild type or gain-of-function mutants of SHP-2 exhibited dampened activities. Increased levels of SHP-2 expression over this range significantly suppressed microtubule organizing center (MTOC)4 polarization and granzyme B release in response to target cells. Interestingly, NK-target cell conjugation was only reduced by overexpressing SHP-2, but not potentiated in SHP-2-silenced cells, indicating that conjugation is not influenced by physiological levels of SHP-2 expression. KIR-dependent inhibition of cytotoxicity was unaffected by significant reductions in SHP-2 levels, presumably because KIR were still capable of recruiting the phosphatase under these limiting conditions. In contrast, the general suppressive effect of SHP-2 on cytotoxicity and cytokine release was much more sensitive to changes in cellular SHP-2 levels. In summary, our studies have identified a new, KIR-independent role for SHP-2 in dampening NK cell activation in response to tumor target cells in a concentration-dependent manner. This suppression of activation impacts MTOC-based cytoskeletal rearrangement and granule release. PMID:19915046

Neuronal effects of nicotine during auditory selective attention.

PubMed

Smucny, Jason; Olincy, Ann; Eichman, Lindsay S; Tregellas, Jason R

2015-06-01

Although the attention-enhancing effects of nicotine have been behaviorally and neurophysiologically well-documented, its localized functional effects during selective attention are poorly understood. In this study, we examined the neuronal effects of nicotine during auditory selective attention in healthy human nonsmokers. We hypothesized to observe significant effects of nicotine in attention-associated brain areas, driven by nicotine-induced increases in activity as a function of increasing task demands. A single-blind, prospective, randomized crossover design was used to examine neuronal response associated with a go/no-go task after 7 mg nicotine or placebo patch administration in 20 individuals who underwent functional magnetic resonance imaging at 3T. The task design included two levels of difficulty (ordered vs. random stimuli) and two levels of auditory distraction (silence vs. noise). Significant treatment × difficulty × distraction interaction effects on neuronal response were observed in the hippocampus, ventral parietal cortex, and anterior cingulate. In contrast to our hypothesis, U and inverted U-shaped dependencies were observed between the effects of nicotine on response and task demands, depending on the brain area. These results suggest that nicotine may differentially affect neuronal response depending on task conditions. These results have important theoretical implications for understanding how cholinergic tone may influence the neurobiology of selective attention.

Barley (Hordeum vulgare) circadian clock genes can respond rapidly to temperature in an EARLY FLOWERING 3-dependent manner

PubMed Central

Ford, Brett; Deng, Weiwei; Clausen, Jenni; Oliver, Sandra; Boden, Scott; Hemming, Megan; Trevaskis, Ben

2016-01-01

An increase in global temperatures will impact future crop yields. In the cereal crops wheat and barley, high temperatures accelerate reproductive development, reducing the number of grains per plant and final grain yield. Despite this relationship between temperature and cereal yield, it is not clear what genes and molecular pathways mediate the developmental response to increased temperatures. The plant circadian clock can respond to changes in temperature and is important for photoperiod-dependent flowering, and so is a potential mechanism controlling temperature responses in cereal crops. This study examines the relationship between temperature, the circadian clock, and the expression of flowering-time genes in barley (Hordeum vulgare), a crop model for temperate cereals. Transcript levels of barley core circadian clock genes were assayed over a range of temperatures. Transcript levels of core clock genes CCA1, GI, PRR59, PRR73, PRR95, and LUX are increased at higher temperatures. CCA1 and PRR73 respond rapidly to a decrease in temperature whereas GI and PRR59 respond rapidly to an increase in temperature. The response of GI and the PRR genes to changes in temperature is lost in the elf3 mutant indicating that their response to temperature may be dependent on a functional ELF3 gene. PMID:27580625

Opiate-induced Changes in Brain Adenosine Levels and Narcotic Drug Responses

PubMed Central

Wu, Manhong; Sahbaie, Peyman; Zheng, Ming; Lobato, Robert; Boison, Detlev; Clark, J. David; Peltz, Gary

2012-01-01

We have very little information about the metabolomic changes that mediate neurobehavioral responses, including addiction. It was possible that opioid-induced metabolomic changes in brain could mediate some of the pharmacodynamic effects of opioids. To investigate this, opiate-induced brain metabolomic responses were profiled using a semi-targeted method in C57BL/6 and 129Sv1 mice, which exhibit extreme differences in their tendency to become opiate dependent. Escalating morphine doses (10–40 mg/kg) administered over a 4-day period selectively induced a two-fold decrease (p<0.00005) in adenosine abundance in the brainstem of C57BL/6 mice, which exhibited symptoms of narcotic drug dependence; but did not decrease adenosine abundance in 129Sv1 mice, which do not exhibit symptoms of dependence. Based on this finding, the effect of adenosine on dependence was investigated in genetically engineered mice with alterations in adenosine tone in the brain and in pharmacologic experiments. Morphine withdrawal behaviors were significantly diminished (P<0.0004) in genetically engineered mice with reduced adenosine tone in the brainstem, and by treatment with an adenosine receptor1 (A1) agonist (2-chloro-N6-cyclopentyladenosine, 0.5 mg/kg) or an A2a receptor (A2a) antagonist (SCH 58261 1 mg/kg). These results indicate that adenosine homeostasis plays a crucial role in narcotic drug responses. Opiate-induced changes in brain adenosine levels may explain many important neurobehavioral features associated with opiate addiction and withdrawal. PMID:23098802

The influence of gravitoinertial force level on oculomotor and perceptual responses to Coriolis, cross-coupling stimulation

NASA Technical Reports Server (NTRS)

Dizio, Paul; Lackner, James R.; Evanoff, John N.

1987-01-01

The goal of the present experiment was to determine whether gravitoinertial force magnitude influences oculomotor and perceptual responses to Coriolis cross-coupling stimulation. Blindfolded subjects who were rotating at constant velocity were asked to make standardized head movements during the free-fall and high-force phases of parabolic flight, and the characteristics of their horizontal nystagmus and the magnitude of their experienced self-motion were measured. Both responses were less intense in the free-fall periods than in the high-force periods. These findings suggest that the response to semicircular canal stimulation depends on the background level of gravitoinertial force.

Cutting edge: double-stranded DNA breaks in the IgV region gene were detected at lower frequency in affinity-maturation impeded GANP-/- mice.

PubMed

Kawatani, Yousuke; Igarashi, Hideya; Matsui, Takeshi; Kuwahara, Kazuhiko; Fujimura, Satoru; Okamoto, Nobukazu; Takagi, Katsumasa; Sakaguchi, Nobuo

2005-11-01

Double-stranded DNA breaks (DSBs) at the IgV region (IgV) genes might be involved in somatic hypermutation and affinity-maturation of the B cell receptor in response to T cell-dependent Ag. By ligation-mediated PCR, we studied IgV DSBs that occurred in mature germinal center B cells in response to nitrophenyl-chicken gamma-globulin in a RAG1-independent, Ag-dependent, and IgV-selective manner. We quantified their levels in GANP-deficient B cells that have impaired generation of high-affinity Ab. GANP-/- B cells showed a decreased level of DSBs with blunt ends than control B cells and, on the contrary, the ganp gene transgenic (GANPTg) B cells showed an increased level. These results suggested that the level of IgV DSBs in germinal center B cells is associated with GANP expression, which is presumably required for B cell receptor affinity maturation.

Modeling the Effect of Olivocochlear Efferents on the Subcortical Envelope Following Response in Humans

DTIC Science & Technology

2016-11-28

olivocochlear reflex (MOCR), a feedback mechanism that controls gain of the outer hair cells, is thought to provide protection and enhancement for a listener in...effectively reduce the outer hair cell gain, depending on the stimulus frequency, level, and timing. Human Envelope Following Responses (EFRs

Hormesis and Paradoxical Effects of Drooping Birch (Betula pendula Roth) Parameters Under Motor Traffic Pollution

PubMed Central

2015-01-01

Various plant indexes are used or recommended for bioindication. However, the nonmonotonic dose–response dependences (hormesis and paradoxical effects) of these indexes are insufficiently explored upon exposure to pollution. We studied the dependences of these Betula pendula indexes on the intensity of motor traffic pollution. Regression analysis did not reveal any dependence of chlorophyll and carotenoid content on traffic intensity (in 2008 and 2010-2013). Lipid peroxidation rate had different versions of paradoxical effects in 2008 and 2010 to 2012 and increased in comparison with control under an increase in pollution level in 2013. In 2010 to 2012, all dose–response dependences for total protein and thiol group content were biphasic and multiphasic paradoxical effects. In 2013, an increase in traffic intensity induced a linear reduction in protein content and an increase in thiol group level in comparison with the control. In most cases, the studied phenological indexes and seed production decreased monotonically in comparison with the control following an increase in traffic intensity. Only in 2010 and 2013, share of fallen leaves had hormesis and paradoxical effect accordingly. Fluctuating asymmetry had a paradoxical effect and hormesis in 2008 and 2012, accordingly, and increased in comparison with the control under an increase in the level of pollution in 2010 to 2011. PMID:26676071

Learning Sustainability by Developing a Solar Dryer for Microalgae Retrieval

ERIC Educational Resources Information Center

Malheiro, Benedita; Ribeiro, Cristina; Silva, Manuel F.; Caetano, Nídia; Paulo Ferreira,; Guedes, Pedro

2015-01-01

The development of nations depends on energy consumption, which is generally based on fossil fuels. This dependency produces irreversible and dramatic effects on the environment, e.g. large greenhouse gas emissions, which in turn cause global warming and climate changes, responsible for the rise of the sea level, floods, and other extreme weather…

A Value-Added Study of a Federal Grant Program in Mathematics for Military Dependent Students

ERIC Educational Resources Information Center

Marquand, Jay C.

2013-01-01

Closing the achievement gap in public education means all students are expected to be learning at grade level. In response to federal mandates requiring schools to attain specific student achievement benchmarks, many schools are placing greater resources into support programs designed to increase student achievement. Military dependent students…

2′,5′-Dihydroxychalcone-induced glutathione is mediated by oxidative stress and kinase signaling pathways

PubMed Central

Kachadourian, Remy; Pugazhenthi, Subbiah; Velmurugan, Kalpana; Backos, Donald S.; Franklin, Christopher C.; McCord, Joe M.; Day, Brian J.

2011-01-01

Hydroxychalcones are naturally occurring compounds that continue to attract considerable interest due to their anti-inflammatory and anti-angiogenic properties. They have been reported to inhibit the synthesis of the inducible nitric oxide (NO) synthase and to induce the expression of heme oxygenase-1 (HO-1). This study examines the mechanisms by which 2′,5′-dihydroxychalcone (2′,5′-DHC) induces an increase in cellular glutathione (GSH) levels using a cell line stably expressing a luciferase reporter gene driven by antioxidant response elements (MCF-7/AREc32). 2′,5′-DHC-induced increase in cellular GSH levels was partially inhibited by the catalytic antioxidant MnTDE-1,3-IP5+, suggesting that reactive oxygen species (ROS) mediate the antioxidant adaptive response. 2′,5′-DHC treatment induced the phosphorylation of c-Jun N-terminal kinase (JNK) pathway that was also inhibited by MnTDE-1,3-IP5+. These findings suggest a ROS-dependent activation of the AP-1 transcriptional response. However, while 2′,5′-DHC triggered the NF-E2-related factor 2 (Nrf2) transcriptional response, co-treatment with MnTDE-1,3-IP5+ did not decrease 2′,5′-DHC-induced Nrf2/ARE activity, showing that this pathway is not dependent on ROS. Moreover, pharmacological inhibitors of mitogen-activated protein (MAP) kinase pathways showed a role for JNK and p38MAPK in mediating the 2′,5′-DHC-induced Nrf2 response. These findings suggest that the 2′,5′-DHC-induced increase in GSH levels results from a combination of ROS-dependent and ROS-independent pathways. PMID:21712085

Cellular Notch responsiveness is defined by phosphoinositide 3-kinase-dependent signals

PubMed Central

Mckenzie, Grahame; Ward, George; Stallwood, Yvette; Briend, Emmanuel; Papadia, Sofia; Lennard, Andrew; Turner, Martin; Champion, Brian; Hardingham, Giles E

2006-01-01

Background Notch plays a wide-ranging role in controlling cell fate, differentiation and development. The PI3K-Akt pathway is a similarly conserved signalling pathway which regulates processes such as differentiation, proliferation and survival. Mice with disrupted Notch and PI3K signalling show phenotypic similarities during haematopoietic cell development, suggesting functional interaction between these pathways. Results We show that cellular responsiveness to Notch signals depends on the activity of the PI3K-Akt pathway in cells as diverse as CHO cells, primary T-cells and hippocampal neurons. Induction of the endogenous PI3K-Akt pathway in CHO cells (by the insulin pathway), in T-cells (via TCR activation) or in neurons (via TrKB activation) potentiates Notch-dependent responses. We propose that the PI3K-Akt pathway exerts its influence on Notch primarily via inhibition of GSK3-beta, a kinase known to phosphorylate and regulate Notch signals. Conclusion The PI3K-Akt pathway acts as a "gain control" for Notch signal responses. Since physiological levels of intracellular Notch are often low, coincidence with PI3K-activation may be crucial for induction of Notch-dependent responses. PMID:16507111

An extract of Agaricus blazei Murill administered orally promotes immune responses in murine leukemia BALB/c mice in vivo.

PubMed

Lin, Jaung-Geng; Fan, Ming-Jen; Tang, Nou-Ying; Yang, Jai-Sing; Hsia, Te-Chun; Lin, Jen-Jyh; Lai, Kuang-Chi; Wu, Rick Sai-Chuen; Ma, Chia-Yu; Wood, W Gibson; Chung, Jing-Gung

2012-03-01

The edible mushroom (fungus) Agaricus blazei Murill (ABM) is a health food in many countries. Importantly, it has been shown to have antitumor and immune effects. There is no available information on ABM-affected immune responses in leukemia mice in vivo. Experimental Design. In this study, the authors investigated the immunopotentiating activities of boiled water-soluble extracts from desiccated ABM in WEHI-3 leukemia mice. The major characteristic of WEHI-3 leukemia mice are enlarged spleens and livers after intraperitoneal injection with murine leukemia WEHI-3 cells. Isolated T cells from spleens of ABM-treated mice resulted in increased T-cell proliferation compared with the untreated control with concanavalin A stimulation. ABM decreased the spleen and liver weights when compared with WEHI-3 leukemia mice and this effect was a dose-dependent response. ABM promoted natural killer cell activity and phagocytosis by macrophage/monocytes in leukemia mice in a dose-dependent manner. ABM also enhanced cytokines such as interleukin (IL)-1β, IL-6, and interferon-γ levels but reduced the level of IL-4 in WEHI-3 leukemia mice. Moreover, ABM increased the levels of CD3 and CD19 but decreased the levels of Mac-3 and CD11b in leukemia mice. The ABM extract is likely to stimulate immunocytes and regulate immune response in leukemia mice in vivo.

A dimensional approach to understanding severity estimates and risk correlates of marijuana abuse and dependence in adults

PubMed Central

WU, LI-TZY; WOODY, GEORGE E.; YANG, CHONGMING; PAN, JENG-JONG; REEVE, BRYCE B.; BLAZER, DAN G.

2012-01-01

While item response theory (IRT) research shows a latent severity trait underlying response patterns of substance abuse and dependence symptoms, little is known about IRT-based severity estimates in relation to clinically relevant measures. In response to increased prevalences of marijuana-related treatment admissions, an elevated level of marijuana potency, and the debate on medical marijuana use, we applied dimensional approaches to understand IRT-based severity estimates for marijuana use disorders (MUDs) and their correlates while simultaneously considering gender- and race/ethnicity-related differential item functioning (DIF). Using adult data from the 2008 National Survey on Drug Use and Health (N=37,897), DSM-IV criteria for MUDs among past-year marijuana users were examined by IRT, logistic regression, and multiple indicators–multiple causes (MIMIC) approaches. Among 6,917 marijuana users, 15% met criteria for a MUD; another 24% exhibited subthreshold dependence. Abuse criteria were highly correlated with dependence criteria (correlation=0.90), indicating unidimensionality; item information curves revealed redundancy in multiple criteria. MIMIC analyses showed that MUD criteria were positively associated with weekly marijuana use, early marijuana use, other substance use disorders, substance abuse treatment, and serious psychological distress. African Americans and Hispanics showed higher levels of MUDs than whites, even after adjusting for race/ethnicity-related DIF. The redundancy in multiple criteria suggests an opportunity to improve efficiency in measuring symptom-level manifestations by removing low-informative criteria. Elevated rates of MUDs among African Americans and Hispanics require research to elucidate risk factors and improve assessments of MUDs for different racial/ethnic groups. PMID:22351489

Stimulatory effect of insulin on 5alpha-reductase type 1 (SRD5A1) expression through an Akt-dependent pathway in ovarian granulosa cells.

PubMed

Kayampilly, Pradeep P; Wanamaker, Brett L; Stewart, James A; Wagner, Carrie L; Menon, K M J

2010-10-01

Elevated levels of 5α-reduced androgens have been shown to be associated with hyperandrogenism and hyperinsulinemia, the leading causes of ovulatory dysfunction in women. 5α-Dihydrotestosterone reduces ovarian granulosa cell proliferation by inhibiting FSH-mediated mitogenic signaling pathways. The present study examined the effect of insulin on 5α-reductase, the enzyme that catalyses the conversion of androgens to their 5α-derivatives. Granulosa cells isolated from immature rat ovaries were cultured in serum-free, phenol red-free DMEM-F12 media and treated with different doses of insulin (0, 0.1, 1.0, and 10.0 μg/ml) for different time intervals up to 12 h. The expression of 5α-reductase type 1 mRNA, the predominant isoform found in granulosa cells, showed a significant (P<0.05) increase in response to the insulin treatment up to 12 h compared with control. The catalytic activity of 5α-reductase enzyme was also stimulated in a dose-depended manner (P<0.05). Inhibiting the Akt-dependent signaling pathway abolished the insulin-mediated increase in 5α-reductase mRNA expression, whereas inhibition of the ERK-dependent pathway had no effect. The dose-dependent increase in 5α-reductase mRNA expression as well as catalytic activity seen in response to insulin treatment was also demonstrated in the human granulosa cell line (KGN). In addition to increased mRNA expression, a dose-dependent increase in 5α-reductase protein expression in response to insulin was also seen in KGN cells, which corroborated well with that of mRNA expression. These results suggest that elevated levels of 5α-reduced androgens seen in hyperinsulinemic conditions might be explained on the basis of a stimulatory effect of insulin on 5α-reductase in granulosa cells. The elevated levels of these metabolites, in turn, might adversely affect growth and proliferation of granulosa cells, thereby impairing follicle growth and ovulation.

Evidence of a Lombard response in migrating humpback whales (Megaptera novaeangliae).

PubMed

Dunlop, Rebecca A; Cato, Douglas H; Noad, Michael J

2014-07-01

The Lombard reflex is an increase in the subject's vocal levels in response to increased noise levels. This functions to maintain an adequate signal-to-noise ratio at the position of the receiver when noise levels vary. While it has been demonstrated in a small number of mammals and birds including some whales, it has not yet been shown to occur in one of the most vocal species of baleen whale, the humpback whale (Megaptera novaeangliae). Humpback whales were simultaneously visually and acoustically tracked (using an array of calibrated hydrophone buoys) as they migrated southward. Source levels of social vocalizations were estimated from measured received levels and a site-specific empirical sound propagation model developed. In total, 226 social vocalizations from 16 passing groups of whales were selected for final analysis. Noise levels were predominantly wind-dependent (from sea surface motion) and ranged from 81 to 108 dB re 1 μPa in the 36 Hz-2.8 kHz band. Vocalization source levels increased by 0.9 dB for every 1 dB increase in wind-dependent background noise levels, with source levels (at 1 m) being maintained ∼60 dB above the noise level.

Signaling of Pigment-Dispersing Factor (PDF) in the Madeira Cockroach Rhyparobia maderae

PubMed Central

Funk, Nico W.; Giese, Maria; Baz, El-Sayed; Stengl, Monika

2014-01-01

The insect neuropeptide pigment-dispersing factor (PDF) is a functional ortholog of vasoactive intestinal polypeptide, the coupling factor of the mammalian circadian pacemaker. Despite of PDF's importance for synchronized circadian locomotor activity rhythms its signaling is not well understood. We studied PDF signaling in primary cell cultures of the accessory medulla, the circadian pacemaker of the Madeira cockroach. In Ca2+ imaging studies four types of PDF-responses were distinguished. In regularly bursting type 1 pacemakers PDF application resulted in dose-dependent long-lasting increases in Ca2+ baseline concentration and frequency of oscillating Ca2+ transients. Adenylyl cyclase antagonists prevented PDF-responses in type 1 cells, indicating that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 pacemakers PDF transiently raised intracellular Ca2+ levels even after blocking adenylyl cyclase activity. In patch clamp experiments the previously characterized types 1–4 could not be identified. Instead, PDF-responses were categorized according to ion channels affected. Application of PDF inhibited outward potassium or inward sodium currents, sometimes in the same neuron. In a comparison of Ca2+ imaging and patch clamp experiments we hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K+ currents. Possibly, this PDF-dependent depolarization underlies PDF-dependent phase advances of pacemakers. Finally, we propose that PDF-dependent concomitant modulation of K+ and Na+ channels in coupled pacemakers causes ultradian membrane potential oscillations as prerequisite to efficient synchronization via resonance. PMID:25269074

High Antibody Responses against Plasmodium falciparum in Immigrants after Extended Periods of Interrupted Exposure to Malaria

PubMed Central

Jiménez, Alfons; Nhabomba, Augusto; Casas-Vila, Núria; Puyol, Laura; Campo, Joseph J.; Manaca, Maria Nelia; Aguilar, Ruth; Pinazo, María-Jesús; Almirall, Mercè; Soler, Cristina; Muñoz, José; Bardají, Azucena; Angov, Evelina; Dutta, Sheetij; Chitnis, Chetan E.; Alonso, Pedro L.; Gascón, Joaquim; Dobaño, Carlota

2013-01-01

Background Malaria immunity is commonly believed to wane in the absence of Plasmodium falciparum exposure, based on limited epidemiological data and short-lived antibody responses in some longitudinal studies in endemic areas. Methods A cross-sectional study was conducted among sub-Saharan African adults residing in Spain for 1 up to 38 years (immigrants) with clinical malaria (n=55) or without malaria (n=37), naïve adults (travelers) with a first clinical malaria episode (n=20) and life-long malaria exposed adults from Mozambique (semi-immune adults) without malaria (n=27) or with clinical malaria (n=50). Blood samples were collected and IgG levels against the erythrocytic antigens AMA-1 and MSP-142 (3D7 and FVO strains), EBA-175 and DBL-α were determined by Luminex. IgG levels against antigens on the surface of infected erythrocytes (IEs) were measured by flow cytometry. Results Immigrants without malaria had lower IgG levels than healthy semi-immune adults regardless of the antigen tested (P≤0.026), but no correlation was found between IgG levels and time since migration. Upon reinfection, immigrants with malaria had higher levels of IgG against all antigens than immigrants without malaria. However, the magnitude of the response compared to semi-immune adults with malaria depended on the antigen tested. Thus, immigrants had higher IgG levels against AMA-1 and MSP-142 (P≤0.015), similar levels against EBA-175 and DBL-α, and lower levels against IEs (P≤0.016). Immigrants had higher IgG levels against all antigens tested compared to travelers (P≤0.001), both with malaria. Conclusions Upon cessation of malaria exposure, IgG responses to malaria-specific antigens were maintained to a large extent, although the conservation and the magnitude of the recall response depended on the nature of the antigen. Studies on immigrant populations can shed light on the factors that determine the duration of malaria specific antibody responses and its effect on protection, with important implications for future vaccine design and public health control measures. PMID:23967347

Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells.

PubMed

Foxman, Ellen F; Storer, James A; Fitzgerald, Megan E; Wasik, Bethany R; Hou, Lin; Zhao, Hongyu; Turner, Paul E; Pyle, Anna Marie; Iwasaki, Akiko

2015-01-20

Most isolates of human rhinovirus, the common cold virus, replicate more robustly at the cool temperatures found in the nasal cavity (33-35 °C) than at core body temperature (37 °C). To gain insight into the mechanism of temperature-dependent growth, we compared the transcriptional response of primary mouse airway epithelial cells infected with rhinovirus at 33 °C vs. 37 °C. Mouse airway cells infected with mouse-adapted rhinovirus 1B exhibited a striking enrichment in expression of antiviral defense response genes at 37 °C relative to 33 °C, which correlated with significantly higher expression levels of type I and type III IFN genes and IFN-stimulated genes (ISGs) at 37 °C. Temperature-dependent IFN induction in response to rhinovirus was dependent on the MAVS protein, a key signaling adaptor of the RIG-I-like receptors (RLRs). Stimulation of primary airway cells with the synthetic RLR ligand poly I:C led to greater IFN induction at 37 °C relative to 33 °C at early time points poststimulation and to a sustained increase in the induction of ISGs at 37 °C relative to 33 °C. Recombinant type I IFN also stimulated more robust induction of ISGs at 37 °C than at 33 °C. Genetic deficiency of MAVS or the type I IFN receptor in infected airway cells permitted higher levels of viral replication, particularly at 37 °C, and partially rescued the temperature-dependent growth phenotype. These findings demonstrate that in mouse airway cells, rhinovirus replicates preferentially at nasal cavity temperature due, in part, to a less efficient antiviral defense response of infected cells at cool temperature.

Possible evidence for re-regulation of HPA axis and brain reward systems over time in treatment in prescription opioid-dependent patients.

PubMed

Bunce, Scott C; Harris, Jonathan D; Bixler, Edward O; Taylor, Megan; Muelly, Emilie; Deneke, Erin; Thompson, Kenneth W; Meyer, Roger E

2015-01-01

There is growing evidence for a neuroadaptive model underlying vulnerability to relapse in opioid dependence. The purpose of this study was to evaluate clinical measures hypothesized to mirror elements of allostatic dysregulation in patients dependent on prescription opioids at 2 time points after withdrawal, compared with healthy control participants. Recently withdrawn (n = 7) prescription opioid-dependent patients were compared with the patients in supervised residential care for 2 to 3 months (extended care; n = 7) and healthy controls (n = 7) using drug cue reactivity, affect-modulated startle response tasks, salivary cortisol, and 8 days of sleep actigraphy. Prefrontal cortex was monitored with functional near-infrared spectroscopy during the cue reactivity task. Startle response results indicated reduced hedonic response to natural rewards among patients recently withdrawn from opioids relative to extended care patients. The recently withdrawn patients showed increased activation to pill stimuli in right dorsolateral prefrontal cortex relative to extended care patients. Cortisol levels were elevated among recently withdrawn patients and intermediate for extended care relative to healthy controls. Actigraphy indicated disturbed sleep between recently withdrawn patients and extended care patients; extended care patients were similar to controls. Dorsolateral prefrontal cortex activation to drug and natural reward cues, startle responses to natural reward cues, day-time cortisol levels, time in bed, and total time spent sleeping were all correlated with the number of days since last drug use (ie, time in supervised residential treatment). These results suggest possible re-regulation of dysregulated hypothalamic-pituitary-adrenal axis and brain reward systems in prescription opioid-dependent patients over the drug-free period in residential treatment.

A stochastic chemical dynamic approach to correlate autoimmunity and optimal vitamin-D range.

PubMed

Roy, Susmita; Shrinivas, Krishna; Bagchi, Biman

2014-01-01

Motivated by several recent experimental observations that vitamin-D could interact with antigen presenting cells (APCs) and T-lymphocyte cells (T-cells) to promote and to regulate different stages of immune response, we developed a coarse grained but general kinetic model in an attempt to capture the role of vitamin-D in immunomodulatory responses. Our kinetic model, developed using the ideas of chemical network theory, leads to a system of nine coupled equations that we solve both by direct and by stochastic (Gillespie) methods. Both the analyses consistently provide detail information on the dependence of immune response to the variation of critical rate parameters. We find that although vitamin-D plays a negligible role in the initial immune response, it exerts a profound influence in the long term, especially in helping the system to achieve a new, stable steady state. The study explores the role of vitamin-D in preserving an observed bistability in the phase diagram (spanned by system parameters) of immune regulation, thus allowing the response to tolerate a wide range of pathogenic stimulation which could help in resisting autoimmune diseases. We also study how vitamin-D affects the time dependent population of dendritic cells that connect between innate and adaptive immune responses. Variations in dose dependent response of anti-inflammatory and pro-inflammatory T-cell populations to vitamin-D correlate well with recent experimental results. Our kinetic model allows for an estimation of the range of optimum level of vitamin-D required for smooth functioning of the immune system and for control of both hyper-regulation and inflammation. Most importantly, the present study reveals that an overdose or toxic level of vitamin-D or any steroid analogue could give rise to too large a tolerant response, leading to an inefficacy in adaptive immune function.

Felix Hoppe-Seyler Lecture 1997. Protective antibody responses against viruses.

PubMed

Zinkernagel, R M

1997-08-01

Neutralizing antibody responses against the acute cytopathic vesicular stomatitis virus (VSV) have been studied in mice to evaluate their general characteristics including specificity, self-/non-self discrimination and memory. IgM responses are generated very early, by day 3 to 4, in a T helper cell-independent fashion and without VSV having polyclonal activating capacities. The order of the glycoprotein tips on the virus envelope (multiple, 8-10 nm distance, paracrystalline) exhibiting the neutralizing determinants are key to this prompt response. These paracrystalline identical multimeric antigens are characteristic of infectious agents and are always reacted against by B cells. Self-antigens that are accessible to B cells in the intact host are either monomeric in serum or mobile multimers on cell surfaces; these configurations need contact dependent or contact independent T help, respectively. Because T help is tolerant against self-antigens, no anti-self B cell responses are usually induced against monomeric self-antigens. If collagen or DNA (rigid multimeric self-antigens) become accessible, however, they may become targets of auto-antibody responses. The antibody repertoire against VSV is partially contained in the germline and partially is generated by somatic mutation; they seem not to undergo affinity-maturation. In any case protection against lethal infection is dependent upon strictly T helper cell dependent IgG generated by day 6 to 7 and reaches a protective level of about 1-10 micrograms/ml. Interesting affinity/avidity and onrate above a minimal threshold are of no apparent advantage for protection in vivo. Maintenance of these antibody levels by antigen depots, and not the presence of memory B cells alone, is key to providing protective immunological memory. Collectively these data suggest that studying biologically important protective antibody responses may modify some of the parameters that have been defined by studying hapten specific antibody responses.

Blood oxygenation level-dependent (BOLD) contrast magnetic resonance imaging (MRI) for prediction of breast cancer chemotherapy response: a pilot study.

PubMed

Jiang, Lan; Weatherall, Paul T; McColl, Roderick W; Tripathy, Debu; Mason, Ralph P

2013-05-01

To determine whether a simple noninvasive method of assessing tumor oxygenation is feasible in the clinical setting and can provide useful, potentially predictive information. Tumor microcirculation and oxygenation play critical roles in tumor growth and responsiveness to cytotoxic treatment and may provide prognostic indicators for cancer therapy. Deoxyhemoglobin is paramagnetic and can serve as an endogenous contrast agent causing signal loss in echo planar magnetic resonance imaging (MRI) (blood oxygenation level-dependent [BOLD]-MRI). We used BOLD-MRI to provide early evaluation of response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MRI was performed on 11 patients with biopsy-proven malignancy. MRI exams were scheduled before, during, and after chemotherapy. The BOLD study applied a 6-minute oxygen breathing challenge. Seven patients successfully completed the exams. Before chemotherapy, BOLD contrast enhancement was observed in all tumors, but the patients, who ultimately had complete pathological response, exhibited a significantly higher BOLD response to oxygen breathing. We have successfully implemented an oxygen-breathing challenge BOLD contrast technique as part of the standard breast MRI exam in patients with locally advanced breast cancer. The preliminary observation that a large BOLD response correlated with better treatment response suggests a predictive capability for BOLD MRI. Copyright © 2012 Wiley Periodicals, Inc.

The immunomodulatory effect of vitamin D in chickens is dose-dependent and influenced by calcium and phosphorus levels.

PubMed

Rodriguez-Lecompte, J C; Yitbarek, A; Cuperus, T; Echeverry, H; van Dijk, A

2016-11-01

Vitamin D requirement is estimated to be higher than recommended values for the first two weeks of a broiler chicken's life, and is heavily dependent on the concentrations of Ca and P in the diet. There are data indicating the beneficial effect of higher vitamin D levels on performance and overall health of the chickens. However, data on the role of higher vitamin D levels on the innate immune response of chickens are limited. Therefore, in the current study, we examined the effect of higher doses of vitamin D supplementation on the innate immune response in broiler chickens receiving optimal or calcium (Ca) and phosphorus (P) deficient diets. Three hundred Ross-308 male broiler chicks were randomly allocated into 60 cages with 5 birds per cage in a 3 × 2 factorial design with three levels of vitamin D and two levels of Ca/P with each experimental diet fed to 10 cages (10 replicates). Quantitative reverse transcription PCR (n = 5) was used to assess Toll-like receptor (TLR2b and 4), cytokine/chemokine (IL-12, IFN-γ, IL-10, IL-4, IL-13, IL-18, CxCLi2) and cathelicidin (CATH1, CATHB1, CATH3) transcription levels in peripheral blood mononuclear cells (PBMCs), spleen, and bursa of Fabricius. Vitamin D supplementation of the Ca and P deficient diet considerably augmented transcription of TLR2b, TLR4, CATH1, and CATHB1 and predominantly Th2 cytokines in spleen. Supplementation of the control diet with vitamin D downregulated TLR4 transcription, and dose-dependently increased CATH1, CATHB1, Th1, and Th2 cytokine transcription (Th2>Th1). All diets downregulated CATH3 transcription. In conclusion, vitamin D or its derivative 25-OH-D 3 both have a robust immunomodulatory property with a more favorable Th2 response, while at the same time enhancing observed Th2 cytokine responses under both optimal and lower Ca and P inclusion levels in the diets of broiler chickens. © 2016 Poultry Science Association Inc.

Density-dependent adjustment of inducible defenses.

PubMed

Tollrian, Ralph; Duggen, Sonja; Weiss, Linda C; Laforsch, Christian; Kopp, Michael

2015-08-03

Predation is a major factor driving evolution, and organisms have evolved adaptations increasing their survival chances. However, most defenses incur trade-offs between benefits and costs. Many organisms save costs by employing inducible defenses as responses to fluctuating predation risk. The level of defense often increases with predator densities. However, individual predation risk should not only depend on predator density but also on the density of conspecifics. If the predator has a saturating functional response one would predict a negative correlation between prey density and individual predation risk and hence defense expression. Here, we tested this hypothesis using six model systems, covering a taxonomic range from protozoa to rotifers and crustaceans. In all six systems, we found that the level of defense expression increased with predator density but decreased with prey density. In one of our systems, i.e. in Daphnia, we further show that the response to prey density is triggered by a chemical cue released by conspecifics and congeners. Our results indicate that organisms adjust the degree of defense to the acute predation risk, rather than merely to predators' densities. Our study suggests that density-dependent defense expression reflects accurate predation-risk assessment and is a general principle in many inducible-defense systems.

Density-dependent adjustment of inducible defenses

PubMed Central

Tollrian, Ralph; Duggen, Sonja; Weiss, Linda C.; Laforsch, Christian; Kopp, Michael

2015-01-01

Predation is a major factor driving evolution, and organisms have evolved adaptations increasing their survival chances. However, most defenses incur trade-offs between benefits and costs. Many organisms save costs by employing inducible defenses as responses to fluctuating predation risk. The level of defense often increases with predator densities. However, individual predation risk should not only depend on predator density but also on the density of conspecifics. If the predator has a saturating functional response one would predict a negative correlation between prey density and individual predation risk and hence defense expression. Here, we tested this hypothesis using six model systems, covering a taxonomic range from protozoa to rotifers and crustaceans. In all six systems, we found that the level of defense expression increased with predator density but decreased with prey density. In one of our systems, i.e. in Daphnia, we further show that the response to prey density is triggered by a chemical cue released by conspecifics and congeners. Our results indicate that organisms adjust the degree of defense to the acute predation risk, rather than merely to predators’ densities. Our study suggests that density-dependent defense expression reflects accurate predation-risk assessment and is a general principle in many inducible-defense systems. PMID:26235428

Stress indicator gene expression profiles, colony dynamics and tissue development of honey bees exposed to sub-lethal doses of imidacloprid in laboratory and field experiments.

PubMed

De Smet, Lina; Hatjina, Fani; Ioannidis, Pavlos; Hamamtzoglou, Anna; Schoonvaere, Karel; Francis, Frédéric; Meeus, Ivan; Smagghe, Guy; de Graaf, Dirk C

2017-01-01

In this study, different context-dependent effects of imidacloprid exposure on the honey bee response were studied. Honey bees were exposed to different concentrations of imidacloprid during a time period of 40 days. Next to these variables, a laboratory-field comparison was conducted. The influence of the chronic exposure on gene expression levels was determined using an in-house developed microarray targeting different immunity-related and detoxification genes to determine stress-related gene expression changes. Increased levels of the detoxification genes encoding, CYP9Q3 and CYT P450, were detected in imidacloprid-exposed honey bees. The different context-dependent effects of imidacloprid exposure on honey bees were confirmed physiologically by decreased hypopharyngeal gland sizes. Honey bees exposed to imidacloprid in laboratory cages showed a general immunosuppression and no detoxification mechanisms were triggered significantly, while honey bees in-field showed a resilient response with an immune stimulation at later time points. However, the treated colonies had a brood and population decline tendency after the first brood cycle in the field. In conclusion, this study highlighted the different context-dependent effects of imidacloprid exposure on the honey bee response. These findings warn for possible pitfalls concerning the generalization of results based on specific experiments with short exposure times. The increased levels of CYT P450 and CYP9Q3 combined with an immune response reaction can be used as markers for bees which are exposed to pesticides in the field.

Stress indicator gene expression profiles, colony dynamics and tissue development of honey bees exposed to sub-lethal doses of imidacloprid in laboratory and field experiments

PubMed Central

Ioannidis, Pavlos; Hamamtzoglou, Anna; Schoonvaere, Karel; Francis, Frédéric; Meeus, Ivan; Smagghe, Guy; de Graaf, Dirk C.

2017-01-01

In this study, different context-dependent effects of imidacloprid exposure on the honey bee response were studied. Honey bees were exposed to different concentrations of imidacloprid during a time period of 40 days. Next to these variables, a laboratory-field comparison was conducted. The influence of the chronic exposure on gene expression levels was determined using an in-house developed microarray targeting different immunity-related and detoxification genes to determine stress-related gene expression changes. Increased levels of the detoxification genes encoding, CYP9Q3 and CYT P450, were detected in imidacloprid-exposed honey bees. The different context-dependent effects of imidacloprid exposure on honey bees were confirmed physiologically by decreased hypopharyngeal gland sizes. Honey bees exposed to imidacloprid in laboratory cages showed a general immunosuppression and no detoxification mechanisms were triggered significantly, while honey bees in-field showed a resilient response with an immune stimulation at later time points. However, the treated colonies had a brood and population decline tendency after the first brood cycle in the field. In conclusion, this study highlighted the different context-dependent effects of imidacloprid exposure on the honey bee response. These findings warn for possible pitfalls concerning the generalization of results based on specific experiments with short exposure times. The increased levels of CYT P450 and CYP9Q3 combined with an immune response reaction can be used as markers for bees which are exposed to pesticides in the field. PMID:28182641

Altered reward expectancy in individuals with recent methamphetamine dependence.

PubMed

Bischoff-Grethe, Amanda; Connolly, Colm G; Jordan, Stephan J; Brown, Gregory G; Paulus, Martin P; Tapert, Susan F; Heaton, Robert K; Woods, Steven P; Grant, Igor

2017-01-01

Chronic methamphetamine use may lead to changes in reward-related function of the ventral striatum and caudate nucleus. Whether methamphetamine-dependent individuals show heightened reactivity to positively valenced stimuli (i.e. positive reinforcement mechanisms), or an exaggerated response to negatively valenced stimuli (i.e. driven by negative reinforcement mechanisms) remains unclear. This study investigated neural functioning of expectancy and receipt for gains and losses in adults with (METH+) and without (METH-) histories of methamphetamine dependence. Participants (17 METH+; 23 METH-) performed a probabilistic feedback expectancy task during blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Participants were given visual cues probabilistically associated with monetary gain, loss, or neutral outcomes. General linear models examined the BOLD response to: (1) anticipation of gains and losses, and (2) gain and loss monetary outcomes. METH+ had less BOLD response to loss anticipation than METH- in the ventral striatum and posterior caudate. METH+ also showed more BOLD response to loss outcomes than to gain outcomes in the anterior and posterior caudate, whereas METH- did not show differential responses to the valence of outcomes. METH+ individuals showed attenuated neural response to anticipated gains and losses, but their response to loss outcomes was greater than to gain outcomes. A decreased response to loss anticipation, along with a greater response to loss outcomes, suggests an altered ability to evaluate future risks and benefits based upon prior experience, which may underlie suboptimal decision-making in METH+ individuals that increases the likelihood of risky behavior.

Altered reward expectancy in individuals with recent methamphetamine dependence

PubMed Central

Bischoff-Grethe, Amanda; Connolly, Colm G; Jordan, Stephan J; Brown, Gregory G; Paulus, Martin P; Tapert, Susan F; Heaton, Robert K; Woods, Steven P; Grant, Igor

2016-01-01

Background Chronic methamphetamine use may lead to changes in reward-related function of the ventral striatum and caudate nucleus. Whether methamphetamine dependent individuals show heightened reactivity to positively valenced stimuli (i.e., positive reinforcement mechanisms), or an exaggerated response to negatively valenced stimuli (i.e., driven by negative reinforcement mechanisms) remains unclear. This study investigated neural functioning of expectancy and receipt for gains and losses in adults with (METH+) and without (METH−) histories of methamphetamine dependence. Methods Participants (17 METH+; 23 METH−) performed a probabilistic feedback expectancy task during blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Participants were given visual cues probabilistically associated with monetary gain, loss, or neutral outcomes. General linear models examined the BOLD response to: (1) anticipation of gains and losses, and (2) gain and loss monetary outcomes. Results METH+ had less BOLD response to loss anticipation than METH− in the ventral striatum and posterior caudate. METH+ also showed more BOLD response to loss outcomes than to gain outcomes in the anterior and posterior caudate, whereas METH− did not show differential responses to the valence of outcomes. Discussion METH+ individuals showed attenuated neural response to anticipated gains and losses, but their response to loss outcomes was greater than to gain outcomes. A decreased response to loss anticipation, along with a greater response to loss outcomes, suggests an altered ability to evaluate future risks and benefits based upon prior experience, which may underlie suboptimal decision-making in METH+ individuals that increases the likelihood of risky behavior. PMID:27649775

Motor function in microgravity: movement in weightlessness

NASA Technical Reports Server (NTRS)

Lackner, J. R.; DiZio, P.

1996-01-01

Microgravity provides unique, though experimentally challenging, opportunities to study motor control. A traditional research focus has been the effects of linear acceleration on vestibular responses to angular acceleration. Evidence is accumulating that the high-frequency vestibulo-ocular reflex (VOR) is not affected by transitions from a 1 g linear force field to microgravity (<1 g); however, it appears that the three-dimensional organization of the VOR is dependent on gravitoinertial force levels. Some of the observed effects of microgravity on head and arm movement control appear to depend on the previously undetected inputs of cervical and brachial proprioception, which change almost immediately in response to alterations in background force levels. Recent studies of post-flight disturbances of posture and locomotion are revealing sensorimotor mechanisms that adjust over periods ranging from hours to weeks.

The long-term consequences of the exposure to increasing gravity levels on the muscular, vestibular and cognitive functions in adult mice.

PubMed

Bojados, Mickael; Jamon, Marc

2014-05-01

Adult male mice C57Bl6/J were exposed to gravity levels between 1G and 4G during three weeks, and the long-term consequences on muscular, vestibular, emotional, and cognitive abilities were evaluated at the functional level to test the hypothesis of a continuum in the response to the increasing gravitational force. In agreement with the hypothesis, the growth of body mass slowed down in relation with the gravity level during the centrifugation, and weight recovery was inversely proportional. On the other hand, the long-term consequences on muscular, vestibular, emotional, and cognitive abilities did not fit the hypothesis of a continuum in the response to the gravity level. The hypergravity acted as endurance training on muscle force until 3G, then became deleterious at 4G. The vestibular reactions were not affected until 4G. Persistent emotional reactions appeared at 3G, and particularly 4G. The mice centrifuged at 3G and 4G showed an impaired spatial learning, probably in relation with the increased level of anxiety, but a greater difficulty was also observed in mice exposed at 2G, suggesting another cause for the impairment of spatial memory. The long-term response to the hypergravity was shown to depend on both the level of gravity and the duration of exposition, with different importance depending on the function considered. Copyright © 2014 Elsevier B.V. All rights reserved.

Contrasting Regulation of NO and ROS in Potato Defense-Associated Metabolism in Response to Pathogens of Different Lifestyles

PubMed Central

Floryszak-Wieczorek, Jolanta; Arasimowicz-Jelonek, Magdalena

2016-01-01

Our research provides new insights into how the low and steady-state levels of nitric oxide (NO) and reactive oxygen species (ROS) in potato leaves are altered after the challenge with the hemibiotroph Phytophthora infestans or the necrotroph Botrytis cinerea, with the subsequent rapid and invader-dependent modification of defense responses with opposite effects. Mainly in the avirulent (avr) P. infestans–potato system, NO well balanced with the superoxide level was tuned with a battery of SA-dependent defense genes, leading to the establishment of the hypersensitive response (HR) successfully arresting the pathogen. Relatively high levels of S-nitrosoglutathione and S-nitrosothiols concentrated in the main vein of potato leaves indicated the mobile function of these compounds as a reservoir of NO bioactivity. In contrast, low-level production of NO and ROS during virulent (vr) P. infestans-potato interactions might be crucial in the delayed up-regulation of PR-1 and PR-3 genes and compromised resistance to the hemibiotrophic pathogen. In turn, B. cinerea triggered huge NO overproduction and governed inhibition of superoxide production by blunting NADPH oxidase. Nevertheless, a relatively high level of H2O2 was found owing to the germin-like activity in cooperation with NO-mediated HR-like cell death in potato genotypes favorable to the necrotrophic pathogen. Moreover, B. cinerea not only provoked cell death, but also modulated the host redox milieu by boosting protein nitration, which attenuated SA production but not SA-dependent defense gene expression. Finally, based on obtained data the organismal cost of having machinery for HR in plant resistance to biotrophs is also discussed, while emphasizing new efforts to identify other components of the NO/ROS cell death pathway and improve plant protection against pathogens of different lifestyles. PMID:27695047

Reward Responsiveness Varies by Smoking Status in Women with a History of Major Depressive Disorder

PubMed Central

Janes, Amy C; Pedrelli, Paola; Whitton, Alexis E; Pechtel, Pia; Douglas, Samuel; Martinson, Max A; Huz, Ilana; Fava, Maurizio; Pizzagalli, Diego A; Evins, A Eden

2015-01-01

Major depressive disorder (MDD) and nicotine dependence are highly comorbid, with studies showing that ~50% of individuals with MDD smoke. The link between these disorders persists even after the clinical symptoms of depression subside, as indicated by high levels of nicotine dependence among individuals with remitted depression (rMDD). Recent evidence indicates that individuals with rMDD show blunted responses to reward as measured by a probabilistic reward task (PRT), which assesses the ability to modify behavior as a function of reward history. Given nicotine's ability to enhance reward responsiveness, individuals with rMDD might smoke to address this persistent reward deficit. However, it is unclear whether smokers with rMDD show enhanced reward responsiveness relative to rMDD individuals who do not smoke. To test this hypothesis, we evaluated reward responsiveness on the PRT in four groups (N=198): individuals with and without rMDD who were or were not nicotine dependent. As hypothesized, rMDD nonsmokers had lower reward responsiveness relative to both control nonsmokers and rMDD smokers; conversely, smokers with rMDD showed behavioral patterns comparable to those without a history of depression. Given nicotine's ability to enhance reward sensitivity, it is possible that nicotine normalizes the otherwise blunted reward responsiveness in individuals with rMDD. Therapies aimed at enhancing this reward-based deficit may be beneficial in the treatment of both nicotine dependence and MDD. PMID:25662839

Hypo-osmotic shock induces nuclear export and proteasome-dependent decrease of UBL5

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

Hatanaka, Ken; Precursory Research for Embryonic Science and Technology; Laboratory of Neurobiophysics, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033

2006-11-24

The osmolarity of body fluid is strictly controlled through the action of diuretic hormones, which are secreted in the hypothalamus. In the mammalian brain, ubiquitin-like 5 (UBL5) is expressed in oxytocin- and vasopressin-positive neurons in the hypothalamus, and these neurons play a role in regulating osmolarity. We examined the dynamics of UBL5 levels in response to hyper- or hypo-osmotic conditions. Hypo-osmotic conditions led to significantly reduced levels of UBL5 both in brain slices from the hypothalamus and in NIH-3T3 cells. This decrease in UBL5 was transcription-independent and proteasome-dependent. Time-course immunocytochemical studies using exogenous UBL5 revealed that the protein was exportedmore » from the nucleus under hypo-osmotic conditions and decreased in a proteasome-dependent manner. This report is the first to describe changes in the intracellular and subcellular localization of UBL5 in response to hypo-osmotic conditions. Our results imply osmoregulation of UBL5.« less

Involvement of Phosphorylated "Apis Mellifera" CREB in Gating a Honeybee's Behavioral Response to an External Stimulus

ERIC Educational Resources Information Center

Gehring, Katrin B.; Heufelder, Karin; Feige, Janina; Bauer, Paul; Dyck, Yan; Ehrhardt, Lea; Kühnemund, Johannes; Bergmann, Anja; Göbel, Josefine; Isecke, Marlene; Eisenhardt, Dorothea

2016-01-01

The transcription factor cAMP-response element-binding protein (CREB) is involved in neuronal plasticity. Phosphorylation activates CREB and an increased level of phosphorylated CREB is regarded as an indicator of CREB-dependent transcriptional activation. In honeybees ("Apis mellifera") we recently demonstrated a particular high…

Neuronal synchrony and the relation between the blood-oxygen-level dependent response and the local field potential

PubMed Central

Nguyen, Mai; Winawer, Jonathan

2017-01-01

The most widespread measures of human brain activity are the blood-oxygen-level dependent (BOLD) signal and surface field potential. Prior studies report a variety of relationships between these signals. To develop an understanding of how to interpret these signals and the relationship between them, we developed a model of (a) neuronal population responses and (b) transformations from neuronal responses into the functional magnetic resonance imaging (fMRI) BOLD signal and electrocorticographic (ECoG) field potential. Rather than seeking a transformation between the two measures directly, this approach interprets each measure with respect to the underlying neuronal population responses. This model accounts for the relationship between BOLD and ECoG data from human visual cortex in V1, V2, and V3, with the model predictions and data matching in three ways: across stimuli, the BOLD amplitude and ECoG broadband power were positively correlated, the BOLD amplitude and alpha power (8–13 Hz) were negatively correlated, and the BOLD amplitude and narrowband gamma power (30–80 Hz) were uncorrelated. The two measures provide complementary information about human brain activity, and we infer that features of the field potential that are uncorrelated with BOLD arise largely from changes in synchrony, rather than level, of neuronal activity. PMID:28742093

Quantitative simulation of intracellular signaling cascades in a Virtual Liver: estimating dose dependent changes in hepatocellular proliferation and apoptosis

EPA Science Inventory

The US EPA Virtual Liver (v-Liver™) is developing an approach to predict dose-dependent hepatotoxicity as an in vivo tissue level response using in vitro data. The v-Liver accomplishes this using an in silico agent-based systems model that dynamically integrates environmental exp...

Determining the right level for your IT security investment.

PubMed

Claunch, Don; McMillan, Mac

2013-05-01

Investing sufficiently in IT security not only is essential for a healthcare organization's protection, but also is a responsibility to patients, and its success depends on its being addressed at all levels of management. Hospital data security breaches have the potential to cost as much as $7 million, including fines, litigation, and damaged reputation. Response and cleanup alone can cost hundreds of thousands of dollars. Developing and following an annual action plan for IT security can lower hospitals' IT security costs in the long run.

An Age-Dependent Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for the Organophosphorus Insecticide Chlorpyrifos in the Preweanling Rat

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

Timchalk, Chuck; Kousba, Ahmed A.; Poet, Torka S.

2007-08-01

Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. In the current study, a modified physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue ChE levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometricallymore » scale both metabolism and tissue ChE levels. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent non-linear increase in CPF-oxon concentration may potentially result from the depletion of non-target B-esterases, and a lower PON-1 metabolic capacity in younger animals. These results indicate that the PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.« less

Limitations of serum ferritin to predict liver iron concentration responses to deferasirox therapy in patients with transfusion-dependent thalassaemia.

PubMed

Porter, John B; Elalfy, Mohsen; Taher, Ali; Aydinok, Yesim; Lee, Szu-Hee; Sutcharitchan, Pranee; El-Ali, Ali; Han, Jackie; El-Beshlawy, Amal

2017-03-01

In transfusion-dependent anaemias, while absolute serum ferritin levels broadly correlate with liver iron concentration (LIC), relationships between trends in these variables are unclear. These relationships are important because serum ferritin changes are often used to adjust or switch chelation regimens when liver magnetic resonance imaging (MRI) is unavailable. This post hoc analysis of the EPIC study compared serum ferritin and LIC in 317 patients with transfusion-dependent thalassaemia before and after 1 yr of deferasirox. Serum ferritin responses (decreases) occurred in 73% of patients, 80% of whom also have decreased LIC. However, 52% of patients without a serum ferritin response did decrease LIC and by >1 mg Fe/g dw (median 3.9) in 77% of cases. Absolute serum ferritin and LIC values correlated significantly only when serum ferritin was <4000 ng/mL (r = 0.59; P < 0.0001) and not at higher levels (≥4000 ng/mL; r = 0.19). Serum ferritin response was accompanied by decreased LIC in 89% and 70% of cases when serum ferritin was <4000 or ≥4000 ng/mL, respectively. As serum ferritin non-response was associated with LIC decrease in over half of patients, use of liver MRI may be particularly useful for differentiating true from apparent non-responders to deferasirox based on serum ferritin trends alone. © 2016 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.

Multiple bottlenecks in hierarchical control of action sequences: what does "response selection" select in skilled typewriting?

PubMed

Yamaguchi, Motonori; Logan, Gordon D; Li, Vanessa

2013-08-01

Does response selection select words or letters in skilled typewriting? Typing performance involves hierarchically organized control processes: an outer loop that controls word level processing, and an inner loop that controls letter (or keystroke) level processing. The present study addressed whether response selection occurs in the outer loop or the inner loop by using the psychological refractory period (PRP) paradigm in which Task1 required typing single words and Task2 required vocal responses to tones. The number of letters (string length) in the words was manipulated to discriminate selection of words from selection of keystrokes. In Experiment 1, the PRP effect depended on string length of words in Task1, suggesting that response selection occurs in the inner loop. To assess contributions of the outer loop, the influence of string length was examined in a lexical-decision task that also involves word encoding and lexical access (Experiment 2), or to-be-typed words were preexposed so outer-loop processing could finish before typing started (Experiment 3). Response time for Task2 (RT2) did not depend on string length with lexical decision, and RT2 still depended on string length with typing preexposed strings. These results support the inner-loop locus of the PRP effect. In Experiment 4, typing was performed as Task2, and the effect of string length on typing RT interacted with stimulus onset asynchrony superadditively, implying that another bottleneck also exists in the outer loop. We conclude that there are at least two bottleneck processes in skilled typewriting. 2013 APA, all rights reserved

Antibodies enhance CXCL10 production during RSV infection of infant and adult immune cells.

PubMed

Vissers, Marloes; Schreurs, Inge; Jans, Jop; Heldens, Jacco; de Groot, Ronald; de Jonge, Marien I; Ferwerda, Gerben

2015-12-01

Respiratory syncytial virus (RSV) bronchiolitis is a major burden in infants below three months of age, when the primary immune response is mainly dependent on innate immunity and maternal antibodies. We investigated the influence of antibodies on innate immunity during RSV infection. PBMCs from infants and adults were stimulated with live RSV and inactivated RSV in combination with antibody-containing and antibody-depleted serum. The immune response was determined by transcriptome analysis and chemokine levels were measured using ELISA and flow cytometry. Microarray data showed that CXCL10 gene transcription was RSV dependent, whereas CXCL11 and IFNα were upregulated in an antibody-dependent manner. Although the presence of antibodies reduces RSV infection rate, it enhances the innate immune response. In adult immune cells, antibodies enhance CXCL10, CXCL11, IFNα and IFNγ production in response to RSV infection. Contrary, in infant immune cells only CXCL10 was enhanced in an antibody-dependent manner. Monocytes are the main source of CXCL10 and they produce CXCL10 in both an antibody- and virus-dependent manner. This study shows that antibodies enhance CXCL10 production in infant immune cells. CXCL10 has been implicated in exuberating the inflammatory response during viral infections and antibodies could therefore play a role in the pathogenesis of RSV infections. Copyright © 2015 Elsevier Ltd. All rights reserved.

Heart rate stress response dampening: the impact of alcohol, family history, and gender on at risk children and siblings.

PubMed

Croissant, Bernhard; Demmel, Ralf; Rist, Fred; Olbrich, Robert

2011-04-01

In the following study we tested the stress response dampening (SRD) model which postulates that stress responses are more likely to be attenuated by alcohol in individuals at risk for alcohol dependence than in persons without that risk. In a laboratory experiment we examined a) if SRD effects exist for both sons and healthy daughters of alcohol dependent fathers, and b) if SRD effects exist for siblings of alcohol dependent males. We recruited 104 subjects at risk and 51 matched control subjects. In a laboratory experiment, study subjects received alcohol in one of two laboratory sessions and a stress paradigm served to elicit heart rate stress responses. Heart rate stress responses were attenuated by alcohol in female family history positive (FHP) and female family history negative (FHN) subjects, however not in males. A multiple regression analysis revealed "Heart Rate Stress Response in the Non-Alcohol Condition" and "Blood Alcohol Level" as significant predictors of SRD. According to our findings, females carry a distinct risk for developing alcohol dependence, regardless of their family history and regardless of their degree of familial relationship. This is an important issue for devising models concerning the development and maintenance of alcohol dependence in females. The study extends the current research literature, which mainly focuses on male subjects at risk, by including female subjects at risk, as well as siblings at risk of both genders. Copyright © 2011 Elsevier B.V. All rights reserved.

Enzymatic glucose sensor compensation for variations in ambient oxygen concentration

NASA Astrophysics Data System (ADS)

Collier, Bradley B.; McShane, Michael J.

2013-02-01

Due to the increasing prevalence of diabetes, research toward painless glucose sensing continues. Oxygen sensitive phosphors with glucose oxidase (GOx) can be used to determine glucose levels indirectly by monitoring oxygen consumption. This is an attractive combination because of its speed and specificity. Packaging these molecules together in "smart materials" for implantation will enable non-invasive glucose monitoring. As glucose levels increase, oxygen levels decrease; consequently, the luminescence intensity and lifetime of the phosphor increase. Although the response of the sensor is dependent on glucose concentration, the ambient oxygen concentration also plays a key role. This could lead to inaccurate glucose readings and increase the risk of hyper- or hypoglycemia. To mitigate this risk, the dependence of hydrogel glucose sensor response on oxygen levels was investigated and compensation methods explored. Sensors were calibrated at different oxygen concentrations using a single generic logistic equation, such that trends in oxygen-dependence were determined as varying parameters in the equation. Each parameter was found to be a function of oxygen concentration, such that the correct glucose calibration equation can be calculated if the oxygen level is known. Accuracy of compensation will be determined by developing an overall calibration, using both glucose and oxygen sensors in parallel, correcting for oxygen fluctuations in real time by intentionally varying oxygen, and calculating the error in actual and predicted glucose levels. While this method was developed for compensation of enzymatic glucose sensors, in principle it can also be implemented with other kinds of sensors utilizing oxidases.

A Neurocomputational model of tonic and phasic dopamine in action selection: A comparison with cognitive deficits in Parkinson’s disease

PubMed Central

Guthrie, M.; Myers, C.E.; Gluck, M.A.

2015-01-01

The striatal dopamine signal has multiple facets; tonic level, phasic rise and fall, and variation of the phasic rise/fall depending on the expectation of reward/punishment. We have developed a network model of the striatal direct pathway using an ionic current level model of the medium spiny neuron that incorporates currents sensitive to changes in the tonic level of dopamine. The model neurons in the network learn action selection based on a novel set of mathematical rules that incorporate the phasic change in the dopamine signal. This network model is capable of learning to perform a sequence learning task that in humans is thought to be dependent on the basal ganglia. When both tonic and phasic levels of dopamine are decreased, as would be expected in unmedicated Parkinson’s disease (PD), the model reproduces the deficits seen in a human PD group off medication. When the tonic level is increased to normal, but with reduced phasic increases and decreases in response to reward and punishment respectively, as would be expected in PD medicated with L-Dopa, the model again reproduces the human data. These findings support the view that the cognitive dysfunctions seen in Parkinson’s disease are not solely due to either the decreased tonic level of dopamine or to the decreased responsiveness of the phasic dopamine signal to reward and punishment, but to a combination of the two factors that varies dependent on disease stage and medication status. PMID:19162084

Community-level consequences of cannibalism.

PubMed

Ohlberger, Jan; Langangen, Oystein; Stenseth, Nils C; Vøllestad, L Asbjørn

2012-12-01

Ecological interactions determine the structure and dynamics of communities and their responses to the environment. Understanding the community-level effects of ecological interactions, such as intra- and interspecifc competition, predation, and cannibalism, is therefore central to ecological theory and ecosystem management. Here, we investigate the community-level consequences of cannibalism in populations with density-dependent maturation and reproduction. We model a stage-structured consumer population with an ontogenetic diet shift to analyze how cannibalism alters the conditions for the invasion and persistence of stage-specific predators and competitors. Our results demonstrate that cannibalistic interactions can facilitate coexistence with other species at both trophic levels. This effect of cannibalism critically depends on the food dependence of the demographic processes. The underlying mechanism is a cannibalism-induced shift in the biomass distribution between the consumer life stages. These findings suggest that cannibalism may alter the structure of ecological communities through its effects on species coexistence.

An investigation of the open-loop amplification of Reynolds number dependent processes by wave distortion

NASA Technical Reports Server (NTRS)

Purdy, K. R.; Ventrice, M. B.; Fang, J.

1972-01-01

Analytical and experimental studies were initiated to determine if the response of a constant temperature hot wire anemometer to acoustic oscillations could serve as an analog to the response of the drop vaporization burning rate process to acoustic oscillations, and, perhaps, also as an analog to any Reynolds number dependent process. The motivation behind this study was a recent analytical study which showed that distorted acoustic oscillations could amplify the open-loop response of vaporization limited combustion. This type of amplification may be the cause of unstable combustion in liquid propellant rocket engines. The analytical results obtained for the constant temperature anemometer are similar in nature to those previously obtained for vaporization limited combustion and indicate that the response is dependent on the amount and type of distortion as well as other factors, such as sound pressure level, Mach number and hot wire temperature. Preliminary results indicate qualitative agreement between theory and experiment.

[The changes in renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome].

PubMed

Cui, Jia; Dou, Jingtao; Yang, Guoqing; Zang, Li; Jin, Nan; Chen, Kang; Du, Jin; Gu, Weijun; Wang, Xianling; Yang, Lijuan; Lyu, Zhaohui; Ba, Jianming; Mu, Yiming; Lu, Juming; Li, Jiangyuan; Pan, Changyu

2015-07-01

Cushing's syndrome is a clinical condition resulting from chronic exposure to excess glucocorticoid. As a consequence, long-term hypercortisolism contributes significantly to the development of systemic disorders by direct and/or indirect effects. The present study was to analyze the changes of renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome on the standard posture test. We retrospectively reviewed 150 patients with histologically confirmed Cushing's syndrome treated at the PLA General Hospital between 2002 and 2014. Among them, 128 patients were diagnosed as adreno-cortico-tropic-hormone (ACTH)-independent Cushing's syndrome, and 22 were ACTH-dependent Cushing's syndrome. All patients were undertaken the posture test. Plasma renin activity (PRA), angiotensin II, plasma aldosterone concertration (PAC) levels were measured before and after the test. Basal plasma PRA [0.5 (0.2,1.3)µg·L(-1)·h(-1), angiotensin II [(48.9±20.1) ng/L] and PAC [(285.0±128.1) pmol/L] levels were within the normal range in supine position. Compared with the subjects with ACTH-independent Cushing's syndrome, the basal PAC levels were higher in subjects with ACTH-dependent Cushing's syndrome [(348.0±130.4) pmol/L vs (274.2±125.0) pmol/L, P<0.05]. However, the PAC response in subjects with ACTH-dependent Cushing's syndrome [(49.7±26.4)%] was significantly lower than that in those with ACTH-independent Cushing's syndrome [(81.2±69.3)%] upon upright posture stimulation (P<0.05). There were no statistical significances in PRA and angiotensin II levels between the two groups. The basal PAC and PRA levels were positively correlated with ACTH, whereas PAC response was negatively correlated with ACTH. The renin-angiotensin-aldosterone-system activity in subjects with Cushing's syndrome was similar to that in normal control. The basal PAC level and its response to upright posture are differently associated with ACTH level in Cushing's syndrome.

Opposite Roles for p38MAPK-Driven Responses and Reactive Oxygen Species in the Persistence and Resolution of Radiation-Induced Genomic Instability

PubMed Central

Werner, Erica; Wang, Huichen; Doetsch, Paul W.

2014-01-01

We report the functional and temporal relationship between cellular phenotypes such as oxidative stress, p38MAPK-dependent responses and genomic instability persisting in the progeny of cells exposed to sparsely ionizing low-Linear Energy Transfer (LET) radiation such as X-rays or high-charge and high-energy (HZE) particle high-LET radiation such as 56Fe ions. We found that exposure to low and high-LET radiation increased reactive oxygen species (ROS) levels as a threshold-like response induced independently of radiation quality and dose. This response was sustained for two weeks, which is the period of time when genomic instability is evidenced by increased micronucleus formation frequency and DNA damage associated foci. Indicators for another persisting response sharing phenotypes with stress-induced senescence, including beta galactosidase induction, increased nuclear size, p38MAPK activation and IL-8 production, were induced in the absence of cell proliferation arrest during the first, but not the second week following exposure to high-LET radiation. This response was driven by a p38MAPK-dependent mechanism and was affected by radiation quality and dose. This stress response and elevation of ROS affected genomic instability by distinct pathways. Through interference with p38MAPK activity, we show that radiation-induced stress phenotypes promote genomic instability. In contrast, exposure to physiologically relevant doses of hydrogen peroxide or increasing endogenous ROS levels with a catalase inhibitor reduced the level of genomic instability. Our results implicate persistently elevated ROS following exposure to radiation as a factor contributing to genome stabilization. PMID:25271419

Copeptin in the diagnosis of vasopressin-dependent disorders of fluid homeostasis.

PubMed

Christ-Crain, Mirjam; Fenske, Wiebke

2016-03-01

Copeptin and arginine vasopressin (AVP) are derived from a common precursor molecule and have equimolar secretion and response to osmotic, haemodynamic and stress-related stimuli. Plasma concentrations of copeptin and AVP in relation to serum osmolality are highly correlated. The physiological functions of AVP with respect to homeostasis of fluid balance, vascular tonus and regulation of the endocrine stress response are well known, but the exact function of copeptin is undetermined. Quantification of AVP can be difficult, but copeptin is stable in plasma and can be easily measured with a sandwich immunoassay. For this reason, copeptin has emerged as a promising marker for the diagnosis of AVP-dependent fluid disorders. Copeptin measurements can enable differentiation between various conditions within the polyuria-polydipsia syndrome. In the absence of prior fluid deprivation, baseline copeptin levels >20 pmol/l identify patients with nephrogenic diabetes insipidus. Conversely, copeptin levels measured upon osmotic stimulation differentiate primary polydipsia from partial central diabetes insipidus. In patients with hyponatraemia, low levels of copeptin together with low urine osmolality identify patients with primary polydipsia, and the ratio of copeptin to urinary sodium can distinguish the syndrome of inappropriate antidiuretic hormone secretion from other AVP-dependent forms of hyponatraemia.

Effects of exercise training and detraining on cutaneous microvascular function in man: the regulatory role of endothelium-dependent dilation in skin vasculature.

PubMed

Wang, Jong-Shyan

2005-01-01

This study investigated how exercise training and detraining affect the cutaneous microvascular function and the regulatory role of endothelium-dependent dilation in skin vasculature. Ten healthy sedentary subjects cycled on an ergometer at 50% of maximal oxygen uptake (VO(2max)) for 30 min daily, 5 days a week, for 8 weeks, and then detrained for 8 weeks. Plasma nitric oxide (NO) metabolites (nitrite plus nitrate) were measured by a microplate fluorometer. The cutaneous microvascular perfusion responses to six graded levels of iontophoretically applied 1% acetylcholine (ACh) and 1% sodium nitroprusside (SNP) in the forearm skin were determined by laser Doppler. After training, (1) resting heart rate and blood pressure were reduced, whereas VO(2max), skin blood flow and cutaneous vascular conductance to acute exercise were enhanced; (2) plasma NO metabolite levels and ACh-induced cutaneous perfusion were increased; (3) skin vascular responses to SNP did not change significantly. However, detraining reversed these effects on cutaneous microvascular function and plasma NO metabolite levels. The results suggest that endothelium-dependent dilation in skin vasculature is enhanced by moderate exercise training and reversed to the pretraining state with detraining.

Human Hippocampal Dynamics during Response Conflict.

PubMed

Oehrn, Carina R; Baumann, Conrad; Fell, Juergen; Lee, Hweeling; Kessler, Henrik; Habel, Ute; Hanslmayr, Simon; Axmacher, Nikolai

2015-08-31

Besides its relevance for declarative memory functions, hippocampal activation has been observed during disambiguation of uncertainty and conflict. Uncertainty and conflict may arise on various levels. On the perceptual level, the hippocampus has been associated with signaling of contextual deviance and disambiguation of similar items (i.e., pattern separation). Furthermore, conflicts can occur on the response level. Animal experiments showed a role of the hippocampus for inhibition of prevailing response tendencies and suppression of automatic stimulus-response mappings, potentially related to increased theta oscillations (3-8 Hz). In humans, a recent fMRI study demonstrated hippocampal involvement in approach-avoidance conflicts. However, the more general significance of hippocampal activity for dealing with response conflicts also on a cognitive level is still unknown. Here, we investigated the role of the hippocampus for response conflict in the Stroop task by combining intracranial electroencephalography (iEEG) recordings from the hippocampus of epilepsy patients with region of interest-based fMRI in healthy participants. Both methods revealed converging evidence that the hippocampus is recruited in a regionally specific manner during response conflict. Moreover, our iEEG data show that this activation depends on theta oscillations and is relevant for successful response conflict resolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

Myostatin induces insulin resistance via Casitas B-lineage lymphoma b (Cblb)-mediated degradation of insulin receptor substrate 1 (IRS1) protein in response to high calorie diet intake.

PubMed

Bonala, Sabeera; Lokireddy, Sudarsanareddy; McFarlane, Craig; Patnam, Sreekanth; Sharma, Mridula; Kambadur, Ravi

2014-03-14

To date a plethora of evidence has clearly demonstrated that continued high calorie intake leads to insulin resistance and type-2 diabetes with or without obesity. However, the necessary signals that initiate insulin resistance during high calorie intake remain largely unknown. Our results here show that in response to a regimen of high fat or high glucose diets, Mstn levels were induced in muscle and liver of mice. High glucose- or fat-mediated induction of Mstn was controlled at the level of transcription, as highly conserved carbohydrate response and sterol-responsive (E-box) elements were present in the Mstn promoter and were revealed to be critical for ChREBP (carbohydrate-responsive element-binding protein) or SREBP1c (sterol regulatory element-binding protein 1c) regulation of Mstn expression. Further molecular analysis suggested that the increased Mstn levels (due to high glucose or fatty acid loading) resulted in increased expression of Cblb in a Smad3-dependent manner. Casitas B-lineage lymphoma b (Cblb) is an ubiquitin E3 ligase that has been shown to specifically degrade insulin receptor substrate 1 (IRS1) protein. Consistent with this, our results revealed that elevated Mstn levels specifically up-regulated Cblb, resulting in enhanced ubiquitin proteasome-mediated degradation of IRS1. In addition, over expression or knock down of Cblb had a major impact on IRS1 and pAkt levels in the presence or absence of insulin. Collectively, these observations strongly suggest that increased glucose levels and high fat diet, both, result in increased circulatory Mstn levels. The increased Mstn in turn is a potent inducer of insulin resistance by degrading IRS1 protein via the E3 ligase, Cblb, in a Smad3-dependent manner.

Season-dependent and independent responses of Mediterranean scrub to light conditions.

PubMed

Zunzunegui, María; Díaz-Barradas, Mari Cruz; Jáuregui, Juan; Rodríguez, Herminia; Álvarez-Cansino, Leonor

2016-05-01

Semi-arid plant species cope with excess of solar radiation with morphological and physiological adaptations that assure their survival when other abiotic stressors interact. At the leaf level, sun and shade plants may differ in the set of traits that regulate environmental stressors. Here, we evaluated if leaf-level physiological seasonal response of Mediterranean scrub species (Myrtus communis, Halimium halimifolium, Rosmarinus officinalis, and Cistus salvifolius) depended on light availability conditions. We aimed to determine which of these responses prevailed independently of the marked seasonality of Mediterranean climate, to define a leaf-level strategy in the scrub community. Thirty six leaf response variables - involving gas exchange, water status, photosystem II photochemical efficiency, photosynthetic pigments and leaf structure - were seasonally measured in sun exposed and shaded plants under field conditions. Physiological responses showed a common pattern throughout the year, in spite of the marked seasonality of the Mediterranean climate and of species-specific differences in the response to light intensity. Variables related to light use, CO2 assimilation, leaf pigment content, and LMA (leaf mass area) presented differences that were consistent throughout the year, although autumn was the season with greater contrast between sun and shade plants. Our data suggest that in Mediterranean scrub shade plants the lutein pool could have an important role in the photoprotection of the photosynthetic tissues. There was a negative linear correlation between the ratio lutein/total chlorophylls and the majority of leaf level variables. The combined effect of abiotic stress factors (light and drought or light and cold) was variable-specific, in some cases enhancing differences between sun and shade plants, while in others leading to unified strategies in all scrub species. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Testosterone influences spatial strategy preferences among adult male rats

PubMed Central

Spritzer, Mark D.; Fox, Elliott C.; Larsen, Gregory D.; Batson, Christopher G.; Wagner, Benjamin A.; Maher, Jack

2013-01-01

Males outperform females on some spatial tasks, and this may be partially due to the effects of sex steroids on spatial strategy preferences. Previous work with rodents indicates that low estradiol levels bias females toward a striatum-dependent response strategy, whereas high estradiol levels bias them toward a hippocampus-dependent place strategy. We tested whether testosterone influenced the strategy preferences in male rats. All subjects were castrated and assigned to one of three daily injection doses of testosterone (0.125, 0.250, or 0.500 mg/rat) or a control group that received daily injections of the drug vehicle. Three different maze protocols were used to determine rats’ strategy preferences. A low dose of testosterone (0.125 mg) biased males toward a motor-response strategy on a T-maze task. In a water maze task in which the platform itself could be used intermittently as a visual cue, a low testosterone dose (0.125 mg) caused a significant increase in the use of a cued-response strategy relative to control males. Results from this second experiment also indicated that males receiving a high dose of testosterone (0.500 mg) were biased toward a place strategy. A third experiment indicated that testosterone dose did not have a strong influence on the ability of rats to use a nearby visual cue (floating ball) in the water maze. For this experiment, all groups seemed to use a combination of place and cued-response strategies. Overall, the results indicate that the effects of testosterone on spatial strategy preference are dose dependent and task dependent. PMID:23597827

Testosterone influences spatial strategy preferences among adult male rats.

PubMed

Spritzer, Mark D; Fox, Elliott C; Larsen, Gregory D; Batson, Christopher G; Wagner, Benjamin A; Maher, Jack

2013-05-01

Males outperform females on some spatial tasks, and this may be partially due to the effects of sex steroids on spatial strategy preferences. Previous work with rodents indicates that low estradiol levels bias females toward a striatum-dependent response strategy, whereas high estradiol levels bias them toward a hippocampus-dependent place strategy. We tested whether testosterone influenced the strategy preferences in male rats. All subjects were castrated and assigned to one of three daily injection doses of testosterone (0.125, 0.250, or 0.500 mg/rat) or a control group that received daily injections of the drug vehicle. Three different maze protocols were used to determine rats' strategy preferences. A low dose of testosterone (0.125 mg) biased males toward a motor-response strategy on a T-maze task. In a water maze task in which the platform itself could be used intermittently as a visual cue, a low testosterone dose (0.125 mg) caused a significant increase in the use of a cued-response strategy relative to control males. Results from this second experiment also indicated that males receiving a high dose of testosterone (0.500 mg) were biased toward a place strategy. A third experiment indicated that testosterone dose did not have a strong influence on the ability of rats to use a nearby visual cue (floating ball) in the water maze. For this experiment, all groups seemed to use a combination of place and cued-response strategies. Overall, the results indicate that the effects of testosterone on spatial strategy preference are dose dependent and task dependent. Copyright © 2013 Elsevier Inc. All rights reserved.

Ocean-state dependency of the equatorial Pacific response to Westerly Wind Events

NASA Astrophysics Data System (ADS)

Puy, martin; Lengaigne, matthieu; Madec, gurvan; Vialard, jerome; Guilyardi, eric

2015-04-01

Short-lived wind events in the equatorial Pacific strongly influence the El Niño/Southern Oscillation (ENSO) evolution. In the first part of this study, we found in observations that both westerly wind events (WWEs) and their easterly wind events (EWEs) counterpart are unambiguously associated with increased Madden Julian oscillation and atmospheric equatorial Rossby waves activity, i.e. that the atmospheric state influences the occurrence probability of WWEs. In the second part, we investigate how the oceanic state modulates the response to these WWEs by applying the same WWE forcing over a interannually-varying ocean state in an OGCM simulation. We find that the amplitude of the SST response, both at the warm pool eastern edge and in the eastern Pacific, can vary by a factor of up to two depending on the ocean state. The sea level and current response are also clearly modulated, with varying contributions of the second and third baroclinic modes depending on the oceanic stratification. We will discuss the mechanisms by which the oceanic state modulates the response to the WWE, and how this could contribute to their impact on ENSO

The role of calcium in the desensitization of capsaicin responses in rat dorsal root ganglion neurons.

PubMed

Koplas, P A; Rosenberg, R L; Oxford, G S

1997-05-15

Capsaicin (Cap) is a pungent extract of the Capsicum pepper family, which activates nociceptive primary sensory neurons. Inward current and membrane potential responses of cultured neonatal rat dorsal root ganglion neurons to capsaicin were examined using whole-cell and perforated patch recording methods. The responses exhibited strong desensitization operationally classified as acute (diminished response during constant Cap exposure) and tachyphylaxis (diminished response to successive applications of Cap). Both acute desensitization and tachyphylaxis were greatly diminished by reductions in external Ca2+ concentration. Furthermore, chelation of intracellular Ca2+ by addition of either EGTA or bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid to the patch pipette attenuated both forms of desensitization even in normal Ca2+. Release of intracellular Ca2+ by caffeine triggered acute desensitization in the absence of extracellular Ca2+, and barium was found to effectively substitute for calcium in supporting desensitization. Cap activated inward current at an ED50 of 728 nM, exhibiting cooperativity (Hill coefficient, 2.2); however, both forms of desensitization were only weakly dependent on [Cap], suggesting a dissociation between activation of Cap-sensitive channels and desensitization. Removal of ATP and GTP from the intracellular solutions resulted in nearly complete tachyphylaxis even with intracellular Ca2+ buffered to low levels, whereas changes in nucleotide levels did not significantly alter the acute form of desensitization. These data suggest a key role for intracellular Ca2+ in desensitization of Cap responses, perhaps through Ca2+-dependent dephosphorylation at a locus that normally sustains Cap responsiveness via ATP-dependent phosphorylation. It also seems that the signaling mechanisms underlying the two forms of desensitization are not identical in detail.

Dose- and time-dependence of the host-mediated response to paclitaxel therapy: a mathematical modeling approach.

PubMed

Benguigui, Madeleine; Alishekevitz, Dror; Timaner, Michael; Shechter, Dvir; Raviv, Ziv; Benzekry, Sebastien; Shaked, Yuval

2018-01-05

It has recently been suggested that pro-tumorigenic host-mediated processes induced in response to chemotherapy counteract the anti-tumor activity of therapy, and thereby decrease net therapeutic outcome. Here we use experimental data to formulate a mathematical model describing the host response to different doses of paclitaxel (PTX) chemotherapy as well as the duration of the response. Three previously described host-mediated effects are used as readouts for the host response to therapy. These include the levels of circulating endothelial progenitor cells in peripheral blood and the effect of plasma derived from PTX-treated mice on migratory and invasive properties of tumor cells in vitro . A first set of mathematical models, based on basic principles of pharmacokinetics/pharmacodynamics, did not appropriately describe the dose-dependence and duration of the host response regarding the effects on invasion. We therefore provide an alternative mathematical model with a dose-dependent threshold, instead of a concentration-dependent one, that describes better the data. This model is integrated into a global model defining all three host-mediated effects. It not only precisely describes the data, but also correctly predicts host-mediated effects at different doses as well as the duration of the host response. This mathematical model may serve as a tool to predict the host response to chemotherapy in cancer patients, and therefore may be used to design chemotherapy regimens with improved therapeutic outcome by minimizing host mediated effects.

Age and meloxicam modify the response of the glutamate vesicular transporters (VGLUTs) after transient global cerebral ischemia in the rat brain.

PubMed

Llorente, Irene L; Pérez-Rodríguez, Diego; Burgin, Taiana C; Gonzalo-Orden, José M; Martínez-Villayandre, Beatriz; Fernández-López, Arsenio

2013-05-01

This study analyzes how age and inflammation modify the response of the vesicular glutamate transporters (VGLUTs), VGLUT1-3 to global brain ischemia/reperfusion (I/R) in brain areas with different I/R vulnerabilities. Global ischemia was induced in 3- and 18-month-old male Sprague-Dawley rats and CA1 and CA3 hippocampal areas, dentate gyrus and cerebral cortex of sham-operated and I/R animals were removed 48 h after insult. Real-time PCR analysis revealed that I/R challenge resulted in a significant decrease of the VGLUT mRNA levels in young animals. Western blot assays showed a lessened age-dependent response to the ischemic damage in VGLUT1 and VGLUT3, while VGLUT2 presented an age and structure-dependent response to challenge. The use of the anti-inflammatory agent meloxicam following challenge showed that COX2 inhibition promotes the expression of VGLUTs in both sham and injured animals, which results in a lessened response to I/R injury. VGLUT1 and VGLUT3 presented an age-dependent response to ischemic damage, while this VGLUT response was age both and structure-dependent. In addition, COX-2 inhibition resulted in an increase of VGLUT1 and VGLUT2 protein amounts both in sham and injured animals together with a lessening of the transporters' response to ischemia. Copyright © 2013 Elsevier Inc. All rights reserved.

The way to her heart? Response to romantic cues is dependent on hunger state and dieting history: An fMRI pilot study.

PubMed

Ely, Alice V; Childress, Anna Rose; Jagannathan, Kanchana; Lowe, Michael R

2015-12-01

Normal weight historical dieters (HDs) are prone to future weight gain, and show higher levels of brain activation in reward-related regions after having eaten than nondieters (NDs) in response to food stimuli (Ely, Childress, Jagannathan, & Lowe, 2014), a similar pattern to that seen in obesity. We hypothesized that HDs are differentially sensitive after eating to rewards in general, and thus extended prior findings by comparing the same groups' brain activation when viewing romantic pictures compared to neutral stimuli while being scanned in a blood oxygenation level-dependent (BOLD) fMRI paradigm in a fasted and fed state. Results show that 1) in fed relative to fasted conditions, both HDs and NDs were more responsive in areas related to reward and 2) in HDs, greater fed versus fasted activation extended to areas linked to perception and goal-directed behavior. HDs relative to NDs were more responsive to romantic cues in the superior frontal gyrus when fasted and the middle temporal gyrus when fed. This pattern of response is similar to HDs' activation when viewing highly palatable food cues, and is consistent with research showing overlapping brain-based responses to sex, drugs and food. Copyright © 2015 Elsevier Ltd. All rights reserved.

Concurrent information affects response inhibition processes via the modulation of theta oscillations in cognitive control networks.

PubMed

Chmielewski, Witold X; Mückschel, Moritz; Dippel, Gabriel; Beste, Christian

2016-11-01

Inhibiting responses is a challenge, where the outcome (partly) depends on the situational context. In everyday situations, response inhibition performance might be altered when irrelevant input is presented simultaneously with the information relevant for response inhibition. More specifically, irrelevant concurrent information may either brace or interfere with response-relevant information, depending on whether these inputs are redundant or conflicting. The aim of this study is to investigate neurophysiological mechanisms and the network underlying such modulations using EEG beamforming as method. The results show that in comparison to a baseline condition without concurrent information, response inhibition performance can be aggravated or facilitated by manipulating the extent of conflict via concurrent input. This depends on whether the requirement for cognitive control is high, as in conflicting trials, or whether it is low, as in redundant trials. In line with this, the total theta frequency power decreases in a right hemispheric orbitofrontal response inhibition network including the SFG, MFG, and SMA, when concurrent redundant information facilitates response inhibition processes. Vice versa, theta activity in a left-hemispheric response inhibition network (i.e., SFG, MFG, and IFG) increases, when conflicting concurrent information compromises response inhibition processes. We conclude that concurrent information bi-directionally shifts response inhibition performance and modulates the network architecture underlying theta oscillations which are signaling different levels of the need for cognitive control.

T-cell-independent and T-cell-dependent antibody responses in patients with chronic renal failure.

PubMed

Beaman, M; Michael, J; MacLennan, I C; Adu, D

1989-01-01

Antibody responses against pneumococcal capsular antigens and tetanus toxoid were measured in 14 patients with chronic renal failure who were managed by continuous ambulatory peritoneal dialysis (CAPD) or haemodialysis (HD) and in eight healthy controls. IgG antipneumococcal responses were predominantly of the IgG2 and to a lesser extent IgG1 subclasses, while the IgG response against tetanus toxoid was largely IgG1 with smaller amounts of IgG4 and IgG3. The post-immunisation serum levels of IgG1 and IgM antibody against both antigens were significantly reduced in the uraemic patients compared with controls (P less than 0.05). All the uraemic patients had normal levels of IgG, IgA and IgM in the serum, but elevated levels of IgG3 prior to immunisation. The mechanisms responsible for the asymmetric depression of antibody responses in uraemia are unclear and may account in part for the increased susceptibility to infection in these patients.

Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder.

PubMed

Szczepanik, Joanna; Nugent, Allison C; Drevets, Wayne C; Khanna, Ashish; Zarate, Carlos A; Furey, Maura L

2016-08-30

The muscarinic antagonist scopolamine produces rapid antidepressant effects in individuals with major depressive disorder (MDD). In healthy subjects, manipulation of acetyl-cholinergic transmission modulates attention in a stimulus-dependent manner. This study tested the hypothesis that baseline amygdalar activity in response to emotional stimuli correlates with antidepressant treatment response to scopolamine and could thus potentially predict treatment outcome. MDD patients and healthy controls performed an attention shifting task involving emotional faces while undergoing functional magnetic resonance imaging (fMRI). We found that blood oxygenation level dependent (BOLD) signal in the amygdala acquired while MDD patients processed sad face stimuli correlated positively with antidepressant response to scopolamine. Amygdalar response to sad faces in MDD patients who did not respond to scopolamine did not differ from that of healthy controls. This suggests that the pre-treatment task elicited amygdalar activity that may constitute a biomarker of antidepressant treatment response to scopolamine. Furthermore, in MDD patients who responded to scopolamine, we observed a post-scopolamine stimulus processing shift towards a pattern demonstrated by healthy controls, indicating a change in stimulus-dependent neural response potentially driven by attenuated cholinergic activity in the amygdala. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Differential responsiveness to a parenting intervention for mothers in substance abuse treatment.

PubMed

Paris, Ruth; Herriott, Anna; Holt, Melissa; Gould, Karen

2015-12-01

This study examines the relationship between levels of psychological distress in substance-dependent mothers and their differential response to a dyadic parent-child intervention. A sample of 66 mothers who were receiving treatment for substance abuse, as well as a simultaneous parenting intervention, were interviewed pre and post-treatment on measures of psychological distress, adult and child trauma history, parental reflective functioning, and child social-emotional development. Additionally, clinicians provided assessments of the parent-child relationships. As anticipated, trauma histories for mothers and children, children's social emotional development, and parental reflective functioning were associated with aspects of maternal psychological distress. Kruskal-Wallis and subsequent Wilcoxson signed rank tests revealed that women with highest levels of baseline psychological distress showed significant improvements in psychological functioning post-treatment while women with moderately elevated levels of psychological distress did not. Women who were most distressed at baseline showed increased levels of parental reflective functioning post-treatment while women with moderate and lower levels of baseline psychological distress showed improvements on clinician-rated assessments of parent-child relationships. Chi Square analyses showed that parents who endorsed the highest levels of distress at baseline reported that their children's risk status regarding social-emotional development decreased post-treatment. Despite similarities in substance dependence, mothers in this sample had different needs and outcomes in the context of this parenting intervention due to variation in mental health. Given this variation, parenting interventions for substance-dependent mothers need to account for the individual differences in levels of psychological distress. Copyright © 2015 Elsevier Ltd. All rights reserved.

Attempting tobacco cessation--an oral physician's perspective.

PubMed

Pai, Anuradha; Prasad, Shesha

2012-01-01

Tobacco use is a global health care problem. Repetitive exposure to nicotine produces neuroadaptation resulting in nicotine dependence. Smoking is associated with a range of diseases, causing high levels of morbidity and mortality and is one of the leading causes of preventable deaths, with more than 4.6 million smokers worldwide dying each year from smoking related illnesses. Stopping smoking has major health benefits. Quitting at any age provides both short and long term benefits. 45 patients attending the outpatient department at the Oxford Dental College, Bangalore, were randomly allocated to three groups of interventions namely placebo, counseling and nicotine replacement therapy (NRT). Initially each one was assessed for carbon monoxide levels using a breath analyser (pico smokerlyser bedfont UK). They were followed up for six months and the carbon monoxide levels were again assessed using the same instrument. The paired t test was used to compare the results before and after the intervention. The scores before the initiation of intervention and after treatment were compared and all three interventions were found to be statistically significant after six months. It was noticed that patients with very low or low dependence followed by high dependence had good response in the placebo group (68% and 47.6% respectively), in the counseling group maximum response was seen in the medium followed by the very low group (61% and 59% respectively), and maximum response was seen in very high followed by the very low group with NRT (78.7% and 60.5% respectively). The inference that can be drawn from the present study is that non-invasive, non pharmacological methods like placebo and counseling are effective in low to medium groups, and NRT is effective with higher nicotine dependence.

Parametric fMRI of paced motor responses uncovers novel whole-brain imaging biomarkers in spinocerebellar ataxia type 3.

PubMed

Duarte, João Valente; Faustino, Ricardo; Lobo, Mercês; Cunha, Gil; Nunes, César; Ferreira, Carlos; Januário, Cristina; Castelo-Branco, Miguel

2016-10-01

Machado-Joseph Disease, inherited type 3 spinocerebellar ataxia (SCA3), is the most common form worldwide. Neuroimaging and neuropathology have consistently demonstrated cerebellar alterations. Here we aimed to discover whole-brain functional biomarkers, based on parametric performance-level-dependent signals. We assessed 13 patients with early SCA3 and 14 healthy participants. We used a combined parametric behavioral/functional neuroimaging design to investigate disease fingerprints, as a function of performance levels, coupled with structural MRI and voxel-based morphometry. Functional magnetic resonance imaging (fMRI) was designed to parametrically analyze behavior and neural responses to audio-paced bilateral thumb movements at temporal frequencies of 1, 3, and 5 Hz. Our performance-level-based design probing neuronal correlates of motor coordination enabled the discovery that neural activation and behavior show critical loss of parametric modulation specifically in SCA3, associated with frequency-dependent cortico/subcortical activation/deactivation patterns. Cerebellar/cortical rate-dependent dissociation patterns could clearly differentiate between groups irrespective of grey matter loss. Our findings suggest functional reorganization of the motor network and indicate a possible role of fMRI as a tool to monitor disease progression in SCA3. Accordingly, fMRI patterns proved to be potential biomarkers in early SCA3, as tested by receiver operating characteristic analysis of both behavior and neural activation at different frequencies. Discrimination analysis based on BOLD signal in response to the applied parametric finger-tapping task significantly often reached >80% sensitivity and specificity in single regions-of-interest.Functional fingerprints based on cerebellar and cortical BOLD performance dependent signal modulation can thus be combined as diagnostic and/or therapeutic targets in hereditary ataxia. Hum Brain Mapp 37:3656-3668, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Dose-response of women's health-related quality of life (HRQoL) and life satisfaction to physical activity.

PubMed

Eime, Rochelle; Harvey, Jack; Payne, Warren

2014-02-01

To examine the dose-response relationship between health related quality of life (HRQoL) and life satisfaction (outcomes) and duration of recreational physical activity (exposure). Further, to explore whether these relationships depend on type of physical activity (PA). 793 Australian rural-living women self-reported on duration of recreational PA; HRQoL via SF-36 Mental Component Summary (MCS) and Physical Component Summary (PCS); and a life satisfaction scale. ANOVAs and ANCOVAs investigated differences in outcomes (MCS, PCS, and life satisfaction) between tertiles of exposure to recreational PA, and types of PA (club sport, gymnasium, walking), with adjustment for potential confounders. A significant positive dose-response relationship was found between PCS and level of PA. Furthermore, this relationship depended on type of PA, with club-sport participants recording higher PCS than non-club-sport participants in all but the highest tertile of exposure. Life satisfaction and MCS were not significantly related to level of PA. Physical health was positively associated with level of recreational PA, with club sport participation contributing greater benefits at low to moderate exposures than participation in gymnasium or walking activities.

Four Transgenerational Demographic Performance of Moina macrocopa Exposed to Chronic Levels of Cadmium.

PubMed

Gama-Flores, José Luis; Huidobro-Salas, María Elena; Sarma, S S S; Nandini, S

2017-01-01

In this study, we quantified intergenerational, demographic variability of Moina macrocopa subjected to cadmium stress. Exposure of M macrocopa to cadmium (0.2, 0.3, and 0.4 mg/L as CdCl 2 ) through 4 consecutive generations revealed changes in demographic responses not only in survivorship variables but also in reproductive parameters. Long-term demographic responses varied differently, depending on the demographic trait and the concentration of heavy metal in the medium. With the exception of generation time, all life history traits were significantly and adversely influenced due to increase in Cd concentrations. The average life span of M macrocopa varied up to 40% depending on Cd level and the generation of exposure. The highest gross reproductive rates were recorded in controls, while the lowest (∼30% less) were recorded at the highest Cd level. Survival-weighted net reproductive rates were reduced by nearly 50% due to Cd toxicity. The rate of population increase per day of M macrocopa was also significantly affected (∼25%) by Cd as compared to controls. This cladoceran showed a dose-response to Cd toxicity with a significance in both magnitude and frequency of offspring production.

Four Transgenerational Demographic Performance of Moina macrocopa Exposed to Chronic Levels of Cadmium

PubMed Central

Gama-Flores, José Luis; Huidobro-Salas, María Elena; Sarma, S.S.S.; Nandini, S.

2017-01-01

In this study, we quantified intergenerational, demographic variability of Moina macrocopa subjected to cadmium stress. Exposure of M macrocopa to cadmium (0.2, 0.3, and 0.4 mg/L as CdCl2) through 4 consecutive generations revealed changes in demographic responses not only in survivorship variables but also in reproductive parameters. Long-term demographic responses varied differently, depending on the demographic trait and the concentration of heavy metal in the medium. With the exception of generation time, all life history traits were significantly and adversely influenced due to increase in Cd concentrations. The average life span of M macrocopa varied up to 40% depending on Cd level and the generation of exposure. The highest gross reproductive rates were recorded in controls, while the lowest (∼30% less) were recorded at the highest Cd level. Survival-weighted net reproductive rates were reduced by nearly 50% due to Cd toxicity. The rate of population increase per day of M macrocopa was also significantly affected (∼25%) by Cd as compared to controls. This cladoceran showed a dose–response to Cd toxicity with a significance in both magnitude and frequency of offspring production. PMID:28835748

Comparative Analytical Study of Evoked and Event Related Potentials as Correlates of Cognitive Processes

DTIC Science & Technology

1990-07-16

lower brain levels, probably precognitive , suggesting the need to distinguish the components in humans that depend on cognition from those that do...definition of the stimulus regime and that much of this response occurs at lower brain levels, probably precognitive , suggesting the need to distinguish the

Brief Report: Anomalous Neural Deactivations and Functional Connectivity during Receptive Language in Autism Spectrum Disorder--A Functional MRI Study

ERIC Educational Resources Information Center

Karten, Ariel; Hirsch, Joy

2015-01-01

Neural mechanisms that underlie language disability in autism spectrum disorder (ASD) have been associated with reduced excitatory processes observed as positive blood oxygen level dependent (BOLD) responses. However, negative BOLD responses (NBR) associated with language and inhibitory processes have been less studied in ASD. In this study,…

A spatial panel ordered-response model with application to the analysis of urban land-use development intensity patterns

NASA Astrophysics Data System (ADS)

Ferdous, Nazneen; Bhat, Chandra R.

2013-01-01

This paper proposes and estimates a spatial panel ordered-response probit model with temporal autoregressive error terms to analyze changes in urban land development intensity levels over time. Such a model structure maintains a close linkage between the land owner's decision (unobserved to the analyst) and the land development intensity level (observed by the analyst) and accommodates spatial interactions between land owners that lead to spatial spillover effects. In addition, the model structure incorporates spatial heterogeneity as well as spatial heteroscedasticity. The resulting model is estimated using a composite marginal likelihood (CML) approach that does not require any simulation machinery and that can be applied to data sets of any size. A simulation exercise indicates that the CML approach recovers the model parameters very well, even in the presence of high spatial and temporal dependence. In addition, the simulation results demonstrate that ignoring spatial dependency and spatial heterogeneity when both are actually present will lead to bias in parameter estimation. A demonstration exercise applies the proposed model to examine urban land development intensity levels using parcel-level data from Austin, Texas.

Signaling of pigment-dispersing factor (PDF) in the Madeira cockroach Rhyparobia maderae.

PubMed

Wei, Hongying; Yasar, Hanzey; Funk, Nico W; Giese, Maria; Baz, El-Sayed; Stengl, Monika

2014-01-01

The insect neuropeptide pigment-dispersing factor (PDF) is a functional ortholog of vasoactive intestinal polypeptide, the coupling factor of the mammalian circadian pacemaker. Despite of PDF's importance for synchronized circadian locomotor activity rhythms its signaling is not well understood. We studied PDF signaling in primary cell cultures of the accessory medulla, the circadian pacemaker of the Madeira cockroach. In Ca²⁺ imaging studies four types of PDF-responses were distinguished. In regularly bursting type 1 pacemakers PDF application resulted in dose-dependent long-lasting increases in Ca²⁺ baseline concentration and frequency of oscillating Ca²⁺ transients. Adenylyl cyclase antagonists prevented PDF-responses in type 1 cells, indicating that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 pacemakers PDF transiently raised intracellular Ca²⁺ levels even after blocking adenylyl cyclase activity. In patch clamp experiments the previously characterized types 1-4 could not be identified. Instead, PDF-responses were categorized according to ion channels affected. Application of PDF inhibited outward potassium or inward sodium currents, sometimes in the same neuron. In a comparison of Ca²⁺ imaging and patch clamp experiments we hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K⁺ currents. Possibly, this PDF-dependent depolarization underlies PDF-dependent phase advances of pacemakers. Finally, we propose that PDF-dependent concomitant modulation of K⁺ and Na⁺ channels in coupled pacemakers causes ultradian membrane potential oscillations as prerequisite to efficient synchronization via resonance.

Time-dependent climate sensitivity and the legacy of anthropogenic greenhouse gas emissions

PubMed Central

Zeebe, Richard E.

2013-01-01

Climate sensitivity measures the response of Earth’s surface temperature to changes in forcing. The response depends on various climate processes that feed back on the initial forcing on different timescales. Understanding climate sensitivity is fundamental to reconstructing Earth’s climatic history as well as predicting future climate change. On timescales shorter than centuries, only fast climate feedbacks including water vapor, lapse rate, clouds, and snow/sea ice albedo are usually considered. However, on timescales longer than millennia, the generally higher Earth system sensitivity becomes relevant, including changes in ice sheets, vegetation, ocean circulation, biogeochemical cycling, etc. Here, I introduce the time-dependent climate sensitivity, which unifies fast-feedback and Earth system sensitivity. I show that warming projections, which include a time-dependent climate sensitivity, exhibit an enhanced feedback between surface warming and ocean CO2 solubility, which in turn leads to higher atmospheric CO2 levels and further warming. Compared with earlier studies, my results predict a much longer lifetime of human-induced future warming (23,000–165,000 y), which increases the likelihood of large ice sheet melting and major sea level rise. The main point regarding the legacy of anthropogenic greenhouse gas emissions is that, even if the fast-feedback sensitivity is no more than 3 K per CO2 doubling, there will likely be additional long-term warming from slow climate feedbacks. Time-dependent climate sensitivity also helps explaining intense and prolonged warming in response to massive carbon release as documented for past events such as the Paleocene–Eocene Thermal Maximum. PMID:23918402

Time-dependent climate sensitivity and the legacy of anthropogenic greenhouse gas emissions.

PubMed

Zeebe, Richard E

2013-08-20

Climate sensitivity measures the response of Earth's surface temperature to changes in forcing. The response depends on various climate processes that feed back on the initial forcing on different timescales. Understanding climate sensitivity is fundamental to reconstructing Earth's climatic history as well as predicting future climate change. On timescales shorter than centuries, only fast climate feedbacks including water vapor, lapse rate, clouds, and snow/sea ice albedo are usually considered. However, on timescales longer than millennia, the generally higher Earth system sensitivity becomes relevant, including changes in ice sheets, vegetation, ocean circulation, biogeochemical cycling, etc. Here, I introduce the time-dependent climate sensitivity, which unifies fast-feedback and Earth system sensitivity. I show that warming projections, which include a time-dependent climate sensitivity, exhibit an enhanced feedback between surface warming and ocean CO2 solubility, which in turn leads to higher atmospheric CO2 levels and further warming. Compared with earlier studies, my results predict a much longer lifetime of human-induced future warming (23,000-165,000 y), which increases the likelihood of large ice sheet melting and major sea level rise. The main point regarding the legacy of anthropogenic greenhouse gas emissions is that, even if the fast-feedback sensitivity is no more than 3 K per CO2 doubling, there will likely be additional long-term warming from slow climate feedbacks. Time-dependent climate sensitivity also helps explaining intense and prolonged warming in response to massive carbon release as documented for past events such as the Paleocene-Eocene Thermal Maximum.

Neural population encoding and decoding of sound source location across sound level in the rabbit inferior colliculus

PubMed Central

Delgutte, Bertrand

2015-01-01

At lower levels of sensory processing, the representation of a stimulus feature in the response of a neural population can vary in complex ways across different stimulus intensities, potentially changing the amount of feature-relevant information in the response. How higher-level neural circuits could implement feature decoding computations that compensate for these intensity-dependent variations remains unclear. Here we focused on neurons in the inferior colliculus (IC) of unanesthetized rabbits, whose firing rates are sensitive to both the azimuthal position of a sound source and its sound level. We found that the azimuth tuning curves of an IC neuron at different sound levels tend to be linear transformations of each other. These transformations could either increase or decrease the mutual information between source azimuth and spike count with increasing level for individual neurons, yet population azimuthal information remained constant across the absolute sound levels tested (35, 50, and 65 dB SPL), as inferred from the performance of a maximum-likelihood neural population decoder. We harnessed evidence of level-dependent linear transformations to reduce the number of free parameters in the creation of an accurate cross-level population decoder of azimuth. Interestingly, this decoder predicts monotonic azimuth tuning curves, broadly sensitive to contralateral azimuths, in neurons at higher levels in the auditory pathway. PMID:26490292

CO2 and nutrient-driven changes across multiple levels of organization in Zostera noltii ecosystems

NASA Astrophysics Data System (ADS)

Martínez-Crego, B.; Olivé, I.; Santos, R.

2014-12-01

Increasing evidence emphasizes that the effects of human impacts on ecosystems must be investigated using designs that incorporate the responses across levels of biological organization as well as the effects of multiple stressors. Here we implemented a mesocosm experiment to investigate how the individual and interactive effects of CO2 enrichment and eutrophication scale-up from changes in primary producers at the individual (biochemistry) or population level (production, reproduction, and/or abundance) to higher levels of community (macroalgae abundance, herbivory, and global metabolism), and ecosystem organization (detritus release and carbon sink capacity). The responses of Zostera noltii seagrass meadows growing in low- and high-nutrient field conditions were compared. In both meadows, the expected CO2 benefits on Z. noltii leaf production were suppressed by epiphyte overgrowth, with no direct CO2 effect on plant biochemistry or population-level traits. Multi-level meadow response to nutrients was faster and stronger than to CO2. Nutrient enrichment promoted the nutritional quality of Z. noltii (high N, low C : N and phenolics), the growth of epiphytic pennate diatoms and purple bacteria, and shoot mortality. In the low-nutrient meadow, individual effects of CO2 and nutrients separately resulted in reduced carbon storage in the sediment, probably due to enhanced microbial degradation of more labile organic matter. These changes, however, had no effect on herbivory or on community metabolism. Interestingly, individual effects of CO2 or nutrient addition on epiphytes, shoot mortality, and carbon storage were attenuated when nutrients and CO2 acted simultaneously. This suggests CO2-induced benefits on eutrophic meadows. In the high-nutrient meadow, a striking shoot decline caused by amphipod overgrazing masked the response to CO2 and nutrient additions. Our results reveal that under future scenarios of CO2, the responses of seagrass ecosystems will be complex and context-dependent, being mediated by epiphyte overgrowth rather than by direct effects on plant biochemistry. Overall, we found that the responses of seagrass meadows to individual and interactive effects of CO2 and nutrient enrichment varied depending on interactions among species and connections between organization levels.

Phylogenetic responses of forest trees to global change.

PubMed

Senior, John K; Schweitzer, Jennifer A; O'Reilly-Wapstra, Julianne; Chapman, Samantha K; Steane, Dorothy; Langley, Adam; Bailey, Joseph K

2013-01-01

In a rapidly changing biosphere, approaches to understanding the ecology and evolution of forest species will be critical to predict and mitigate the effects of anthropogenic global change on forest ecosystems. Utilizing 26 forest species in a factorial experiment with two levels each of atmospheric CO2 and soil nitrogen, we examined the hypothesis that phylogeny would influence plant performance in response to elevated CO2 and nitrogen fertilization. We found highly idiosyncratic responses at the species level. However, significant, among-genetic lineage responses were present across a molecularly determined phylogeny, indicating that past evolutionary history may have an important role in the response of whole genetic lineages to future global change. These data imply that some genetic lineages will perform well and that others will not, depending upon the environmental context.

T-dependent activation of resting B cells mediated by concanavalin A.

PubMed

Ratcliffe, M J; Julius, M H

1984-03-01

In cultures containing long-term cultured lines of antigen-specific helper T (Th) cells, normal unprimed B cells and concanavalin A (Con A), induction of B cells to immunoglobulin secretion and DNA synthesis was observed. The plaque-forming cell (PFC) response was large (frequently greater than 75 000 PFC/10(6) input B cells) demonstrating the polyspecific nature of the response. Con A-mediated maturation and induction to DNA synthesis of responding B cells was completely Th cell dependent and inhibited with methyl-alpha-D-mannoside. Both resting and blasted B cells, separated by Percoll density centrifugation, were induced to DNA synthesis and immunoglobulin secretion. Responses were completely unrestricted by the B cell major histocompatibility complex, even at the level of the resting B cell. The polyclonal nature of the response taken together with the Con A-mediated bypassing of T cell specificity and restricting haplotype indicates that this response is analogous to lectin-mediated cytotoxicity.

[Responsibility for damage and anger].

PubMed

Schmitt, M; Hoser, K; Schwenkmezger, P

1991-01-01

Anger about frustration or damage was assumed to depend on how much responsibility can be attributed to the perpetrator. This hypothesis was tested experimentally (N = 120). Drawing upon constituents of the action concept (e.g. free will), three everyday situations (e.g. being obstructed while driving) were varied with regard to responsibility. Twenty subjects each were asked to imagine the three situations from one of the six levels of responsibility and to indicate how angry they would feel. In addition to state anger, anger in, anger out, and anger control were assessed. When trait anger was controlled for, state anger as well as anger out increased as a function of the perpetrator's responsibility, whereas anger control decreased. These results were in line with theoretical expectations. They demonstrate that the expression of anger is subject to social norms and depends largely on the situation. This finding complements original assumptions on the trait-like nature of anger in, anger out, and anger control.

Arsenic induced progesterone production in a caspase-3-dependent manner and changed redox status in preovulatory granulosa cells.

PubMed

Yuan, Xiao-Hua; Lu, Cai-Ling; Yao, Nan; An, Li-Sha; Yang, Bai-Qing; Zhang, Chuan-Ling; Ma, Xu

2012-01-01

Arsenic contamination is a principal environmental health threat throughout the world. However, little is known about the effect of arsenic on steroidogenesis in granulosa cells (GCs). We found that the treatment of preovulatory GCs with arsenite stimulated progesterone production. A significant increase in serum level of progesterone was observed in female Sprague-Dawley rats following arsenite treatment at a dose of 10 mg/L/rat/day for 7 days. Further experiments demonstrated that arsenite treatment did not change the level of intracellular cyclic AMP (cAMP) or phosphorylated ERK1/2 in preovulatory GCs; however, progesterone production was significantly decreased when cAMP-dependent protein kinase (PKA) or ERK1/2 pathway was inhibited. This implied that the effect of arsenite on progesterone production may require cAMP/PKA and ERK1/2 signaling but not depend on them. Furthermore, we found that arsenite decreased intracellular reactive oxygen species (ROS) but increased the antioxidant glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm) in parallel to the changes in progesterone production. Progesterone antagonist blocked the arsenic-stimulated increase of GSH levels. Arsenite treatment induced caspase-3 activation, although no apoptosis was observed. Inhibition of caspase-3 activity significantly decreased progesterone production stimulated by arsenite or follicle-stimulating hormone (FSH). GSH depletion with buthionine sulfoximine led to cell apoptosis in response to arsenite treatment. Collectively, this study demonstrated for the first time that arsenite stimulates progesterone production through cleaved/active caspase-3-dependent pathway, and the increase of GSH level promoted by progesterone production may protect GCs against apoptosis and maintain the steroidogenesis of GCs in response to arsenite treatment. Copyright © 2011 Wiley Periodicals, Inc.

c-Myc and AMPK Control Cellular Energy Levels by Cooperatively Regulating Mitochondrial Structure and Function

PubMed Central

Edmunds, Lia R.; Sharma, Lokendra; Wang, Huabo; Kang, Audry; d’Souza, Sonia; Lu, Jie; McLaughlin, Michael; Dolezal, James M.; Gao, Xiaoli; Weintraub, Susan T.; Ding, Ying; Zeng, Xuemei; Yates, Nathan; Prochownik, Edward V.

2015-01-01

The c-Myc (Myc) oncoprotein and AMP-activated protein kinase (AMPK) regulate glycolysis and oxidative phosphorylation (Oxphos) although often for different purposes. Because Myc over-expression depletes ATP with the resultant activation of AMPK, we explored the potential co-dependency of and cross-talk between these proteins by comparing the consequences of acute Myc induction in ampk+/+ (WT) and ampk-/- (KO) murine embryo fibroblasts (MEFs). KO MEFs showed a higher basal rate of glycolysis than WT MEFs and an appropriate increase in response to activation of a Myc-estrogen receptor (MycER) fusion protein. However, KO MEFs had a diminished ability to increase Oxphos, mitochondrial mass and reactive oxygen species in response to MycER activation. Other differences between WT and KO MEFs, either in the basal state or following MycER induction, included abnormalities in electron transport chain function, levels of TCA cycle-related oxidoreductases and cytoplasmic and mitochondrial redox states. Transcriptional profiling of pathways pertinent to glycolysis, Oxphos and mitochondrial structure and function also uncovered significant differences between WT and KO MEFs and their response to MycER activation. Finally, an unbiased mass-spectrometry (MS)-based survey capable of quantifying ~40% of all mitochondrial proteins, showed about 15% of them to be AMPK- and/or Myc-dependent in their steady state. Significant differences in the activities of the rate-limiting enzymes pyruvate kinase and pyruvate dehydrogenase, which dictate pyruvate and acetyl coenzyme A abundance, were also differentially responsive to Myc and AMPK and could account for some of the differences in basal metabolite levels that were also detected by MS. Thus, Myc and AMPK are highly co-dependent and appear to engage in significant cross-talk across numerous pathways which support metabolic and ATP-generating functions. PMID:26230505

Acoustical evaluation of preschool classrooms

NASA Astrophysics Data System (ADS)

Yang, Wonyoung; Hodgson, Murray

2003-10-01

An investigation was made of the acoustical environments in the Berwick Preschool, Vancouver, in response to complaints by the teachers. Reverberation times (RT), background noise levels (BNL), and in-class sound levels (Leq) were measured for acoustical evaluation in the classrooms. With respect to the measured RT and BNL, none of the classrooms in the preschool were acceptable according to the criteria relevant to this study. A questionnaire was administered to the teachers to assess their subjective responses to the acoustical and nonacoustical environments of the classrooms. Teachers agreed that the nonacoustical environments in the classrooms were fair, but that the acoustical environments had problems. Eight different classroom configurations were simulated to improve the acoustical environments, using the CATT room acoustical simulation program. When the surface absorption was increased, both the RT and speech levels decreased. RASTI was dependent on the volumes of the classrooms when the background noise levels were high; however, it depended on the total absorption of the classrooms when the background noise levels were low. Ceiling heights are critical as well. It is recommended that decreasing the volume of the classrooms is effective. Sound absorptive materials should be added to the walls or ceiling.

Movement ecology: size-specific behavioral response of an invasive snail to food availability.

PubMed

Snider, Sunny B; Gilliam, James F

2008-07-01

Immigration, emigration, migration, and redistribution describe processes that involve movement of individuals. These movements are an essential part of contemporary ecological models, and understanding how movement is affected by biotic and abiotic factors is important for effectively modeling ecological processes that depend on movement. We asked how phenotypic heterogeneity (body size) and environmental heterogeneity (food resource level) affect the movement behavior of an aquatic snail (Tarebia granifera), and whether including these phenotypic and environmental effects improves advection-diffusion models of movement. We postulated various elaborations of the basic advection diffusion model as a priori working hypotheses. To test our hypotheses we measured individual snail movements in experimental streams at high- and low-food resource treatments. Using these experimental movement data, we examined the dependency of model selection on resource level and body size using Akaike's Information Criterion (AIC). At low resources, large individuals moved faster than small individuals, producing a platykurtic movement distribution; including size dependency in the model improved model performance. In stark contrast, at high resources, individuals moved upstream together as a wave, and body size differences largely disappeared. The model selection exercise indicated that population heterogeneity is best described by the advection component of movement for this species, because the top-ranked model included size dependency in advection, but not diffusion. Also, all probable models included resource dependency. Thus population and environmental heterogeneities both influence individual movement behaviors and the population-level distribution kernels, and their interaction may drive variation in movement behaviors in terms of both advection rates and diffusion rates. A behaviorally informed modeling framework will integrate the sentient response of individuals in terms of movement and enhance our ability to accurately model ecological processes that depend on animal movement.

Cellular density-dependent down-regulation of EP4 prostanoid receptors via the up-regulation of hypoxia-inducible factor-1α in HCA-7 human colon cancer cells.

PubMed

Otake, Sho; Yoshida, Kenji; Seira, Naofumi; Sanchez, Christopher M; Regan, John W; Fujino, Hiromichi; Murayama, Toshihiko

2015-02-01

Increases in prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) levels are features of colon cancer. Among the different E-type prostanoid receptor subtypes, EP4 receptors are considered to play a crucial role in carcinogenesis by, for example, inducing COX-2 when stimulated with PGE2. However, EP4 receptor levels and PGE2-induced cellular responses are inconsistent among the cellular conditions. Therefore, the connections responsible for the expression of EP4 receptors were investigated in the present study by focusing on cell density-induced hypoxia-inducible factor-1α (HIF-1α). The expression of EP4 receptors was examined using immunoblot analysis, quantitative polymerase chain reaction, and reporter gene assays in HCA-7 human colon cancer cells with different cellular densities. The involvement of HIF-1α and its signaling pathways were also examined by immunoblot analysis, reporter gene assays, and with siRNA. We here demonstrated that EP4 receptors as well as EP4 receptor-mediated COX-2 expression levels decreased with an increase in cellular density. In contrast, HIF-1α levels increased in a cellular density-dependent manner. The knockdown of HIF-1α by siRNA restored the expression of EP4 receptors and EP4 receptor-mediated COX-2 in cells at a high density. Thus, the cellular density-dependent increase observed in HIF-1α expression levels reduced the expression of COX-2 by decreasing EP4 receptor levels. This novel regulation mechanism for the expression of EP4 receptors by HIF-1α may provide an explanation for the inconsistent actions of PGE2. The expression levels of EP4 receptors may vary depending on cellular density, which may lead to the differential activation of their signaling pathways by PGE2. Thus, cellular density-dependent PGE2-mediated signaling may determine the fate/stage of cancer cells, i.e., the surrounding environments could define the fate/stage of malignancies associated with colon cancer.

Cellular density-dependent down-regulation of EP4 prostanoid receptors via the up-regulation of hypoxia-inducible factor-1α in HCA-7 human colon cancer cells

PubMed Central

Otake, Sho; Yoshida, Kenji; Seira, Naofumi; Sanchez, Christopher M; Regan, John W; Fujino, Hiromichi; Murayama, Toshihiko

2015-01-01

Increases in prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) levels are features of colon cancer. Among the different E-type prostanoid receptor subtypes, EP4 receptors are considered to play a crucial role in carcinogenesis by, for example, inducing COX-2 when stimulated with PGE2. However, EP4 receptor levels and PGE2-induced cellular responses are inconsistent among the cellular conditions. Therefore, the connections responsible for the expression of EP4 receptors were investigated in the present study by focusing on cell density-induced hypoxia-inducible factor-1α (HIF-1α). The expression of EP4 receptors was examined using immunoblot analysis, quantitative polymerase chain reaction, and reporter gene assays in HCA-7 human colon cancer cells with different cellular densities. The involvement of HIF-1α and its signaling pathways were also examined by immunoblot analysis, reporter gene assays, and with siRNA. We here demonstrated that EP4 receptors as well as EP4 receptor-mediated COX-2 expression levels decreased with an increase in cellular density. In contrast, HIF-1α levels increased in a cellular density-dependent manner. The knockdown of HIF-1α by siRNA restored the expression of EP4 receptors and EP4 receptor-mediated COX-2 in cells at a high density. Thus, the cellular density-dependent increase observed in HIF-1α expression levels reduced the expression of COX-2 by decreasing EP4 receptor levels. This novel regulation mechanism for the expression of EP4 receptors by HIF-1α may provide an explanation for the inconsistent actions of PGE2. The expression levels of EP4 receptors may vary depending on cellular density, which may lead to the differential activation of their signaling pathways by PGE2. Thus, cellular density-dependent PGE2-mediated signaling may determine the fate/stage of cancer cells, i.e., the surrounding environments could define the fate/stage of malignancies associated with colon cancer. PMID:25692008

The effects of administration of monoamine oxidase-B inhibitors on rat striatal neurone responses to dopamine.

PubMed Central

Berry, M D; Scarr, E; Zhu, M Y; Paterson, I A; Juorio, A V

1994-01-01

1. (-)-Deprenyl has been shown to potentiate rat striatal neurone responses to dopamine agonists at doses not altering dopamine metabolism. Since there are a number of effects of (-)-deprenyl which could result in this phenomenon, we have investigated the effects of MDL 72,145 and Ro 19-6327, whose only common effect with (-)-deprenyl is an inhibition of monoamine oxidase-B (MAO-B), on rat striatal neurone responses to dopamine and on striatal dopamine metabolism. 2. Using in vivo electrophysiology, i.p. injection of either MDL 72,145 or Ro 19-6327 was found to produce a dose-dependent potentiation of striatal neurone responses to dopamine but not gamma-aminobutyric acid. 3. Neurochemical investigations revealed that this occurred at doses (0.25-1 mg kg-1) which, while not affecting levels of dopamine or its metabolites, 3,4-dihydroxyphenylacetic acid or homovanillic acid, did cause a significant, dose-dependent, elevation in striatal levels of the putative neuromodulator, 2-phenylethylamine (PE). 4. Inhibition of PE synthesis by i.p. injection of the aromatic L-amino acid decarboxylase inhibitor, NSD 1015, produced a reversal of the effects of MDL 72,145 and Ro 19-6327. 5. Neurochemical analysis revealed this to occur at a dose of NSD 1015 (10 mg kg-1) selective for reduction of elevated PE levels. 6. These results suggest that PE can act as a neuromodulator of dopaminergic responses and that MAO-B inhibitors may potentiate neuronal responses to dopamine via the indirect mechanism of elevation of PE following MAO-B inhibition. PMID:7889269

Normalization of neuronal responses in cortical area MT across signal strengths and motion directions

PubMed Central

Xiao, Jianbo; Niu, Yu-Qiong; Wiesner, Steven

2014-01-01

Multiple visual stimuli are common in natural scenes, yet it remains unclear how multiple stimuli interact to influence neuronal responses. We investigated this question by manipulating relative signal strengths of two stimuli moving simultaneously within the receptive fields (RFs) of neurons in the extrastriate middle temporal (MT) cortex. Visual stimuli were overlapping random-dot patterns moving in two directions separated by 90°. We first varied the motion coherence of each random-dot pattern and characterized, across the direction tuning curve, the relationship between neuronal responses elicited by bidirectional stimuli and by the constituent motion components. The tuning curve for bidirectional stimuli showed response normalization and can be accounted for by a weighted sum of the responses to the motion components. Allowing nonlinear, multiplicative interaction between the two component responses significantly improved the data fit for some neurons, and the interaction mainly had a suppressive effect on the neuronal response. The weighting of the component responses was not fixed but dependent on relative signal strengths. When two stimulus components moved at different coherence levels, the response weight for the higher-coherence component was significantly greater than that for the lower-coherence component. We also varied relative luminance levels of two coherently moving stimuli and found that MT response weight for the higher-luminance component was also greater. These results suggest that competition between multiple stimuli within a neuron's RF depends on relative signal strengths of the stimuli and that multiplicative nonlinearity may play an important role in shaping the response tuning for multiple stimuli. PMID:24899674

The Small RNA GcvB Promotes Mutagenic Break Repair by Opposing the Membrane Stress Response

PubMed Central

Barreto, Brittany; Rogers, Elizabeth; Xia, Jun; Frisch, Ryan L.; Richters, Megan; Fitzgerald, Devon M.

2016-01-01

ABSTRACT Microbes and human cells possess mechanisms of mutagenesis activated by stress responses. Stress-inducible mutagenesis mechanisms may provide important models for mutagenesis that drives host-pathogen interactions, antibiotic resistance, and possibly much of evolution generally. In Escherichia coli, repair of DNA double-strand breaks is switched to a mutagenic mode, using error-prone DNA polymerases, via the SOS DNA damage and general (σS) stress responses. We investigated small RNA (sRNA) clients of Hfq, an RNA chaperone that promotes mutagenic break repair (MBR), and found that GcvB promotes MBR by allowing a robust σS response, achieved via opposing the membrane stress (σE) response. Cells that lack gcvB were MBR deficient and displayed reduced σS-dependent transcription but not reduced σS protein levels. The defects in MBR and σS-dependent transcription in ΔgcvB cells were alleviated by artificially increasing σS levels, implying that GcvB promotes mutagenesis by allowing a normal σS response. ΔgcvB cells were highly induced for the σE response, and blocking σE response induction restored both mutagenesis and σS-promoted transcription. We suggest that GcvB may promote the σS response and mutagenesis indirectly, by promoting membrane integrity, which keeps σE levels lower. At high levels, σE might outcompete σS for binding RNA polymerase and so reduce the σS response and mutagenesis. The data show the delicate balance of stress response modulation of mutagenesis. IMPORTANCE Mutagenesis mechanisms upregulated by stress responses promote de novo antibiotic resistance and cross-resistance in bacteria, antifungal drug resistance in yeasts, and genome instability in cancer cells under hypoxic stress. This paper describes the role of a small RNA (sRNA) in promoting a stress-inducible-mutagenesis mechanism, mutagenic DNA break repair in Escherichia coli. The roles of many sRNAs in E. coli remain unknown. This study shows that ΔgcvB cells, which lack the GcvB sRNA, display a hyperactivated membrane stress response and reduced general stress response, possibly because of sigma factor competition for RNA polymerase. This results in a mutagenic break repair defect. The data illuminate a function of GcvB sRNA in opposing the membrane stress response, and thus indirectly upregulating mutagenesis. PMID:27698081

The Small RNA GcvB Promotes Mutagenic Break Repair by Opposing the Membrane Stress Response.

PubMed

Barreto, Brittany; Rogers, Elizabeth; Xia, Jun; Frisch, Ryan L; Richters, Megan; Fitzgerald, Devon M; Rosenberg, Susan M

2016-12-15

Microbes and human cells possess mechanisms of mutagenesis activated by stress responses. Stress-inducible mutagenesis mechanisms may provide important models for mutagenesis that drives host-pathogen interactions, antibiotic resistance, and possibly much of evolution generally. In Escherichia coli, repair of DNA double-strand breaks is switched to a mutagenic mode, using error-prone DNA polymerases, via the SOS DNA damage and general (σ S ) stress responses. We investigated small RNA (sRNA) clients of Hfq, an RNA chaperone that promotes mutagenic break repair (MBR), and found that GcvB promotes MBR by allowing a robust σ S response, achieved via opposing the membrane stress (σ E ) response. Cells that lack gcvB were MBR deficient and displayed reduced σ S -dependent transcription but not reduced σ S protein levels. The defects in MBR and σ S -dependent transcription in ΔgcvB cells were alleviated by artificially increasing σ S levels, implying that GcvB promotes mutagenesis by allowing a normal σ S response. ΔgcvB cells were highly induced for the σ E response, and blocking σ E response induction restored both mutagenesis and σ S -promoted transcription. We suggest that GcvB may promote the σ S response and mutagenesis indirectly, by promoting membrane integrity, which keeps σ E levels lower. At high levels, σ E might outcompete σ S for binding RNA polymerase and so reduce the σ S response and mutagenesis. The data show the delicate balance of stress response modulation of mutagenesis. Mutagenesis mechanisms upregulated by stress responses promote de novo antibiotic resistance and cross-resistance in bacteria, antifungal drug resistance in yeasts, and genome instability in cancer cells under hypoxic stress. This paper describes the role of a small RNA (sRNA) in promoting a stress-inducible-mutagenesis mechanism, mutagenic DNA break repair in Escherichia coli The roles of many sRNAs in E. coli remain unknown. This study shows that ΔgcvB cells, which lack the GcvB sRNA, display a hyperactivated membrane stress response and reduced general stress response, possibly because of sigma factor competition for RNA polymerase. This results in a mutagenic break repair defect. The data illuminate a function of GcvB sRNA in opposing the membrane stress response, and thus indirectly upregulating mutagenesis. Copyright © 2016 Barreto et al.

Cryptochrome, Phytochrome, and Anthocyanin Production

PubMed Central

Mancinelli, Alberto L.; Rossi, Federica; Moroni, Anna

1991-01-01

Anthocyanin production in cabbage (Brassica oleracea L.) and tomato (Lycopersicon esculentum Mill.) seedlings exposed to prolonged irradiations was studied under conditions that allowed discrimination, within certain limits, between the contribution of cryptochrome and phytochrome in the photoregulation of the response. The results of the study provide confirming evidence for the involvement of cryptochrome and direct evidence for a significant contribution of cryptochrome to the fluence rate dependence of the response to blue. The results provide some preliminary, direct indication for an interaction between cryptochrome and phytochrome in the photoregulation of anthocyanin production in seedlings exposed to the prolonged irradiations required for a high level of expression of the response. The type and degree of interaction between the two photoreceptors vary significantly, depending on the species and experimental conditions. PMID:16668301

The impact of dependent-care responsibility and gender on work attitudes.

PubMed

Buffardi, L C; Smith, J L; O'Brien, A S; Erdwins, C J

1999-10-01

On the basis of a survey of 18,120 federal employees in dual-income households, six 5-stage hierarchical multiple regression analyses, controlling for 10 demographic variables, assessed the impact of child care, elder care, and gender on work-family balance and various facets of job satisfaction. Elder-care responsibility was associated with lower levels of satisfaction with perceived organizational support, pay, leave benefits, and work-family balance, whereas the negative main effects of child care were limited to leave benefits and work-family balance. However, child-care responsibility also interacted with gender: Its negative influence was greater on women's work-family balance and leave satisfaction. Decrements in satisfaction associated with dependent care on the "sandwich generation" were additive, not interactive.

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

Akhrymuk, Ivan; Frolov, Ilya; Frolova, Elena I., E-mail: evfrolova@UAB.edu

Alphaviruses are a family of positive-strand RNA viruses that circulate on all continents between mosquito vectors and vertebrate hosts. Despite a significant public health threat, their biology is not sufficiently investigated, and the mechanisms of alphavirus replication and virus–host interaction are insufficiently understood. In this study, we have applied a variety of experimental systems to further understand the mechanism by which infected cells detect replicating alphaviruses. Our new data strongly suggest that activation of the antiviral response by alphavirus-infected cells is determined by the integrity of viral genes encoding proteins with nuclear functions, and by the presence of two cellularmore » pattern recognition receptors (PRRs), RIG-I and MDA5. No type I IFN response is induced in their absence. The presence of either of these PRRs is sufficient for detecting virus replication. However, type I IFN activation in response to pathogenic alphaviruses depends on the basal levels of RIG-I or MDA5. - Highlights: • Both RIG-I and MDA5 detect alphavirus replication. • Alphavirus-induced transcriptional shutoff affects type I IFN induction. • Sensing of alphavirus replication by RIG-I and MDA5 depends on their concentrations. • High basal level of RIG-I and MDA5 allows IFN induction by pathogenic alphaviruses. • This dependence determines the discrepancy between the in vivo and in vitro data.« less

Tetrodotoxin-dependent glutamate release in the rat nucleus accumbens during concurrent presentation of appetitive and conditioned aversive stimuli.

PubMed

Saulskaya, Natalia B; Soloviova, Nina A

2004-12-30

In vivo microdialysis combined with a high-performance liquid chromatography was used to monitor extracellular glutamate (GLU) levels in the nucleus accumbens (N.Acc) of Sprague-Dawley rats during their behavioral responses to the concurrent presentation of appetitive and conditioned aversive stimuli. The presentation of a highly palatable diet followed by a tone previously paired with footshock to rats trained to take a pellet of the diet under these experimental conditions resulted in a marked and short lasting increase in extracellular glutamate, whereas the tone alone had no effect. A similar increase of the glutamate release was observed during the presentation of a piece of rubber instead of the diet. In both cases, the increase in extracellular glutamate was completely prevented by intra-accumbal infusions through the dialysis probe of 1 microM tetrodotoxin (a voltage-dependent Na(+) channel blocker), whereas (S)-4-carboxyphenylglycine (a cystine/glutamate exchange blocker, 5 microM) had no effect. The data obtained suggest that behavioral responses to unpredicted change in motivational value of expected reward appear to be associated with an increase of the extracellular glutamate level in the nucleus accumbens, and impulse-dependent synaptic release, rather than non-vesicular glutamate release via cystine/glutamate exchange, is responsible for this phenomenon.

The effects of the activation of the inner-hair-cell basolateral K+ channels on auditory nerve responses.

PubMed

Altoè, Alessandro; Pulkki, Ville; Verhulst, Sarah

2018-07-01

The basolateral membrane of the mammalian inner hair cell (IHC) expresses large voltage and Ca 2+ gated outward K + currents. To quantify how the voltage-dependent activation of the K + channels affects the functionality of the auditory nerve innervating the IHC, this study adopts a model of mechanical-to-neural transduction in which the basolateral K + conductances of the IHC can be made voltage-dependent or not. The model shows that the voltage-dependent activation of the K + channels (i) enhances the phase-locking properties of the auditory fiber (AF) responses; (ii) enables the auditory nerve to encode a large dynamic range of sound levels; (iii) enables the AF responses to synchronize precisely with the envelope of amplitude modulated stimuli; and (iv), is responsible for the steep offset responses of the AFs. These results suggest that the basolateral K + channels play a major role in determining the well-known response properties of the AFs and challenge the classical view that describes the IHC membrane as an electrical low-pass filter. In contrast to previous models of the IHC-AF complex, this study ascribes many of the AF response properties to fairly basic mechanisms in the IHC membrane rather than to complex mechanisms in the synapse. Copyright © 2018 Elsevier B.V. All rights reserved.

Independent predictors of reliability between full time employee-dependent acquisition of functional outcomes compared to non-full time employee-dependent methodologies: a prospective single institutional study.

PubMed

Adogwa, Owoicho; Elsamadicy, Aladine A; Cheng, Joseph; Bagley, Carlos

2016-03-01

The prospective acquisition of reliable patient-reported outcomes (PROs) measures demonstrating the effectiveness of spine surgery, or lack thereof, remains a challenge. The aims of this study are to compare the reliability of functional outcomes metrics obtained using full time employee (FTE) vs. non-FTE-dependent methodologies and to determine the independent predictors of response reliability using non FTE-dependent methodologies. One hundred and nineteen adult patients (male: 65, female: 54) undergoing one- and two-level lumbar fusions at Duke University Medical Center were enrolled in this prospective study. Enrollment criteria included available demographic, clinical and baseline functional outcomes data. All patients were administered two similar sets of baseline questionnaires-(I) phone interviews (FTE-dependent) and (II) hardcopy in clinic (patient self-survey, non-FTE-dependent). All patients had at least a two-week washout period between phone interviews and in-clinic self-surveys to minimize effect of recall. Questionnaires included Oswestry disability index (ODI) and Visual Analog Back and Leg Pain Scale (VAS-BP/LP). Reliability was assessed by the degree to which patient responses to baseline questionnaires differed between both time points. About 26.89% had a history an anxiety disorder and 28.57% reported a history of depression. At least 97.47% of patients had a High School Diploma or GED, with 49.57% attaining a 4-year college degree or post-graduate degree. 29.94% reported full-time employment and 14.28% were on disability. There was a very high correlation between baseline PRO's data captured between FTE-dependent compared to non-FTE-dependent methodologies (r=0.89). In a multivariate logistic regression model, the absence of anxiety and depression, higher levels of education (college or greater) and full-time employment, were independently associated with high response reliability using non-FTE-dependent methodologies. Our study suggests that capturing health-related quality of life data using non-FTE-dependent methodologies is highly reliable and maybe a more cost-effective alternative. Well-educated patients who are employed full-time appear to be the most reliable.

Strong negative terahertz photoconductivity in photoexcited graphene

NASA Astrophysics Data System (ADS)

Fu, Maixia; Wang, Xinke; Ye, Jiasheng; Feng, Shengfei; Sun, Wenfeng; Han, Peng; Zhang, Yan

2018-01-01

Terahertz (THz) response of a chemical vapor deposited graphene on a quartz substrate has been investigated by using an ultrafast optical-pump THz-probe spectroscopy. Without photoexcitation, the frequency-dependence optical conductivity shows a strong carrier response owing to the intrinsically doped graphene. Upon photoexcitation, an enhancement in THz transmission is observed and the transmission increases nonlinearly with the increase of pump power, which is rooted in a reduction of intrinsic conductivity arising from the strong enhancement of carrier scattering rather than THz emission occurrence. The modulation depth of 18.8% was experimentally achieved, which is more than four times greater than that of the previous reported. The photoinduced response here highlights the variety of response possible in graphene depending on the sample quality, carrier mobility and doping level. The graphene provides promising applications in high-performance THz modulators and THz photoelectric devices.

Implementation of Improved Transverse Shear Calculations and Higher Order Laminate Theory Into Strain Rate Dependent Analyses of Polymer Matrix Composites

NASA Technical Reports Server (NTRS)

Zhu, Lin-Fa; Kim, Soo; Chattopadhyay, Aditi; Goldberg, Robert K.

2004-01-01

A numerical procedure has been developed to investigate the nonlinear and strain rate dependent deformation response of polymer matrix composite laminated plates under high strain rate impact loadings. A recently developed strength of materials based micromechanics model, incorporating a set of nonlinear, strain rate dependent constitutive equations for the polymer matrix, is extended to account for the transverse shear effects during impact. Four different assumptions of transverse shear deformation are investigated in order to improve the developed strain rate dependent micromechanics model. The validities of these assumptions are investigated using numerical and theoretical approaches. A method to determine through the thickness strain and transverse Poisson's ratio of the composite is developed. The revised micromechanics model is then implemented into a higher order laminated plate theory which is modified to include the effects of inelastic strains. Parametric studies are conducted to investigate the mechanical response of composite plates under high strain rate loadings. Results show the transverse shear stresses cannot be neglected in the impact problem. A significant level of strain rate dependency and material nonlinearity is found in the deformation response of representative composite specimens.

Stress and the Development of Cognitive Vulnerabilities to Depression Explain Sex Differences in Depressive Symptoms during Adolescence

PubMed Central

Hamilton, Jessica L.; Stange, Jonathan P.; Abramson, Lyn Y.; Alloy, Lauren B.

2014-01-01

Although cognitive vulnerabilities to depression have received considerable empirical support, little research has evaluated the differential development of cognitive vulnerabilities in adolescent girls and boys. The current study examined the role of stressful life events, as well as sex differences in reactivity and exposure to stress, in the development of negative cognitive style and rumination in a multi-wave study of 382 adolescents. Path analyses indicated that interpersonal dependent stress predicted higher prospective levels of negative cognitive styles and rumination. Additionally, girls’ greater exposure to interpersonal dependent stress explained their higher levels of rumination, which accounted for girls’ higher levels of depressive symptoms than boys. These findings suggest that interpersonal dependent stress is a significant risk factor for the formation of cognitive vulnerabilities to depression during adolescence, and that the sex difference in depressive symptoms may result from girls’ greater exposure to interpersonal dependent stress and ruminative response style than boys. PMID:26509106

The Yeast Copper Response Is Regulated by DNA Damage

PubMed Central

Dong, Kangzhen; Addinall, Stephen G.; Lydall, David

2013-01-01

Copper is an essential but potentially toxic redox-active metal, so the levels and distribution of this metal are carefully regulated to ensure that it binds to the correct proteins. Previous studies of copper-dependent transcription in the yeast Saccharomyces cerevisiae have focused on the response of genes to changes in the exogenous levels of copper. We now report that yeast copper genes are regulated in response to the DNA-damaging agents methyl methanesulfonate (MMS) and hydroxyurea by a mechanism(s) that requires the copper-responsive transcription factors Mac1 and AceI, copper superoxide dismutase (Sod1) activity, and the Rad53 checkpoint kinase. Furthermore, in copper-starved yeast, the response of the Rad53 pathway to MMS is compromised due to a loss of Sod1 activity, consistent with the model that yeast imports copper to ensure Sod1 activity and Rad53 signaling. Crucially, the Mac1 transcription factor undergoes changes in its redox state in response to changing levels of copper or MMS. This study has therefore identified a novel regulatory relationship between cellular redox, copper homeostasis, and the DNA damage response in yeast. PMID:23959798

Nalmefene Reduces Reward Anticipation in Alcohol Dependence: An Experimental Functional Magnetic Resonance Imaging Study.

PubMed

Quelch, Darren R; Mick, Inge; McGonigle, John; Ramos, Anna C; Flechais, Remy S A; Bolstridge, Mark; Rabiner, Eugenii; Wall, Matthew B; Newbould, Rexford D; Steiniger-Brach, Björn; van den Berg, Franz; Boyce, Malcolm; Østergaard Nilausen, Dorrit; Breuning Sluth, Lasse; Meulien, Didier; von der Goltz, Christoph; Nutt, David; Lingford-Hughes, Anne

2017-06-01

Nalmefene is a µ and δ opioid receptor antagonist, κ opioid receptor partial agonist that has recently been approved in Europe for treating alcohol dependence. It offers a treatment approach for alcohol-dependent individuals with "high-risk drinking levels" to reduce their alcohol consumption. However, the neurobiological mechanism underpinning its effects on alcohol consumption remains to be determined. Using a randomized, double-blind, placebo-controlled, within-subject crossover design we aimed to determine the effect of a single dose of nalmefene on striatal blood oxygen level-dependent (BOLD) signal change during anticipation of monetary reward using the monetary incentive delay task following alcohol challenge. Twenty-two currently heavy-drinking, non-treatment-seeking alcohol-dependent males were recruited. The effect of single dose nalmefene (18 mg) on changes in a priori defined striatal region of interest BOLD signal change during reward anticipation compared with placebo was investigated using functional magnetic resonance imaging. Both conditions were performed under intravenous alcohol administration (6% vol/vol infusion to achieve a target level of 80 mg/dL). Datasets from 18 participants were available and showed that in the presence of the alcohol infusion, nalmefene significantly reduced the BOLD response in the striatal region of interest compared with placebo. Nalmefene did not alter brain perfusion. Nalmefene blunts BOLD response in the mesolimbic system during anticipation of monetary reward and an alcohol infusion. This is consistent with nalmefene's actions on opioid receptors, which modulate the mesolimbic dopaminergic system, and provides a neurobiological basis for its efficacy. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Evaluation of Selected Immunomodulatory Glycoproteins as an Adjunct to Cancer Immunotherapy

PubMed Central

Sekhon, Bhagwant Kaur; Li, Yiming; Devi, Parimala B.; Nammi, Srinivas; Fan, Kei

2016-01-01

Polysaccharopeptide (PSP), from Coriolus versicolor, has been used widely as an adjuvant to chemotherapy with demonstrated anti-tumor and broad immunomodulating effects. While PSP’s mechanism of action still remains unknown, its enhanced immunomodulatory potential with acacia gum is of great interest. Acacia gum, which also contains polysaccharides and glycoproteins, has been demonstrated to be immunopotentiating. To elucidate whether PSP directly activates T-cell-dependent B-cell responses in vivo, we used a well-established hapten carrier system (Nitrophenyl-chicken gamma globulin (NP-CGG)). 6-week C57BL/6 male mice were immunised with 50 μg of NP25-CGG alum precipitate intraperitoneally. Mice were gavaged daily with 50mg/kg PSP in a vehicle containing acacia gum and sacrificed at days 0, 4, 7, 10, 14 and 21. ELISA was used to measure the total and relative hapten-specific anti-NP IgA, IgM and IgG titre levels compared to the controls. It was found that PSP, combined with acacia gum, significantly increased total IgG titre levels at day 4 (P< 0.05), decreased IgM titre levels at days 4 and 21 (P< 0.05) with no alterations observed in the IgA or IgE titre levels at any of the time points measured. Our results suggest that while PSP combined with acacia gum appears to exert weak immunological effects through specific T-cell dependent B-cell responses, they are likely to be broad and non-specific which supports the current literature on PSP. We report for the first time the application of a well-established hapten-carrier system that can be used to characterise and delineate specific T-cell dependent B-cell responses of potential immunomodulatory glycoprotein-based herbal medicines combinations in vivo. PMID:26799072

The current state of GMO governance: are we ready for GM animals?

PubMed

Vàzquez-Salat, Núria; Salter, Brian; Smets, Greet; Houdebine, Louis-Marie

2012-01-01

Given the history of GMO conflict and debate, the GM animal future is dependent on the response of the regulatory landscape and its associated range of interest groups at national, regional and international levels. Focusing on the EU and the USA, this article examines the likely form of that multi-level response, the increased role of cultural values, the contribution of new and existing interest groups and the consequent implications for the commercialization of both green and red GM animal biotechnology. Copyright © 2012. Published by Elsevier Inc.

Alternative Splicing of Barley Clock Genes in Response to Low Temperature

PubMed Central

Calixto, Cristiane P. G.; Simpson, Craig G.; Waugh, Robbie; Brown, John W. S.

2016-01-01

Alternative splicing (AS) is a regulated mechanism that generates multiple transcripts from individual genes. It is widespread in eukaryotic genomes and provides an effective way to control gene expression. At low temperatures, AS regulates Arabidopsis clock genes through dynamic changes in the levels of productive mRNAs. We examined AS in barley clock genes to assess whether temperature-dependent AS responses also occur in a monocotyledonous crop species. We identify changes in AS of various barley core clock genes including the barley orthologues of Arabidopsis AtLHY and AtPRR7 which showed the most pronounced AS changes in response to low temperature. The AS events modulate the levels of functional and translatable mRNAs, and potentially protein levels, upon transition to cold. There is some conservation of AS events and/or splicing behaviour of clock genes between Arabidopsis and barley. In addition, novel temperature-dependent AS of the core clock gene HvPPD-H1 (a major determinant of photoperiod response and AtPRR7 orthologue) is conserved in monocots. HvPPD-H1 showed a rapid, temperature-sensitive isoform switch which resulted in changes in abundance of AS variants encoding different protein isoforms. This novel layer of low temperature control of clock gene expression, observed in two very different species, will help our understanding of plant adaptation to different environments and ultimately offer a new range of targets for plant improvement. PMID:27959947

Ozone sensitivity in hybrid poplar correlates with insensitivity to both salicylic acid and jasmonic acid. The role of programmed cell death in lesion formation.

PubMed

Koch, J R; Creelman, R A; Eshita, S M; Seskar, M; Mullet, J E; Davis, K R

2000-06-01

Our earlier studies demonstrated that the ozone-sensitive hybrid poplar clone NE-388 displays an attenuated level of ozone-, wound-, and phytopathogen-induced defense gene expression. To determine if this reduced gene activation involves signal transduction pathways dependent on salicylic acid (SA) and/or jasmonic acid (JA), we compared the responses of NE-388 and an ozone-tolerant clone, NE-245, to these signal molecules. JA levels increased in both clones in response to ozone, but only minimal increases in SA levels were measured for either clone. Treatment with SA and methyl jasmonate induced defense gene expression only in NE-245, indicating that NE-388 is insensitive to these signal molecules. DNA fragmentation, an indicator of programmed cell death (PCD), was detected in NE-245 treated with either ozone or an avirulent phytopathogen, but was not detected in NE-388. We conclude that these clones undergo two distinct mechanisms of ozone-induced lesion formation. In NE-388, lesions appear to be due to toxic cell death resulting from a limited ability to perceive and subsequently activate SA- and/or JA-mediated antioxidant defense responses. In NE-245, SA-dependent PCD precedes lesion formation via a process related to the PCD pathway activated by phytopathogenic bacteria. These results support the hypothesis that ozone triggers a hypersensitive response.

Ozone Sensitivity in Hybrid Poplar Correlates with Insensitivity to Both Salicylic Acid and Jasmonic Acid. The Role of Programmed Cell Death in Lesion Formation1

PubMed Central

Koch, Jennifer Riehl; Creelman, Robert A.; Eshita, Steven M.; Seskar, Mirjana; Mullet, John E.; Davis, Keith R.

2000-01-01

Our earlier studies demonstrated that the ozone-sensitive hybrid poplar clone NE-388 displays an attenuated level of ozone-, wound-, and phytopathogen-induced defense gene expression. To determine if this reduced gene activation involves signal transduction pathways dependent on salicylic acid (SA) and/or jasmonic acid (JA), we compared the responses of NE-388 and an ozone-tolerant clone, NE-245, to these signal molecules. JA levels increased in both clones in response to ozone, but only minimal increases in SA levels were measured for either clone. Treatment with SA and methyl jasmonate induced defense gene expression only in NE-245, indicating that NE-388 is insensitive to these signal molecules. DNA fragmentation, an indicator of programmed cell death (PCD), was detected in NE-245 treated with either ozone or an avirulent phytopathogen, but was not detected in NE-388. We conclude that these clones undergo two distinct mechanisms of ozone-induced lesion formation. In NE-388, lesions appear to be due to toxic cell death resulting from a limited ability to perceive and subsequently activate SA- and/or JA-mediated antioxidant defense responses. In NE-245, SA-dependent PCD precedes lesion formation via a process related to the PCD pathway activated by phytopathogenic bacteria. These results support the hypothesis that ozone triggers a hypersensitive response. PMID:10859179

Mapping glucose-mediated gut-to-brain signalling pathways in humans.

PubMed

Little, Tanya J; McKie, Shane; Jones, Richard B; D'Amato, Massimo; Smith, Craig; Kiss, Orsolya; Thompson, David G; McLaughlin, John T

2014-08-01

Previous fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. Changes in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250ml) of: 1M glucose+predosing with dexloxiglumide (CCK1 receptor antagonist), 1M glucose+placebo, or 0.9% saline (control)+placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose+dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. Glucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway. Copyright © 2014. Published by Elsevier Inc.

SIZ1-Dependent Post-Translational Modification by SUMO Modulates Sugar Signaling and Metabolism in Arabidopsis thaliana.

PubMed

Castro, Pedro Humberto; Verde, Nuno; Lourenço, Tiago; Magalhães, Alexandre Papadopoulos; Tavares, Rui Manuel; Bejarano, Eduardo Rodríguez; Azevedo, Herlânder

2015-12-01

Post-translational modification mechanisms function as switches that mediate the balance between optimum growth and the response to environmental stimuli, by regulating the activity of key proteins. SUMO (small ubiquitin-like modifier) attachment, or sumoylation, is a post-translational modification that is essential for the plant stress response, also modulating hormonal circuits to co-ordinate developmental processes. The Arabidopsis SUMO E3 ligase SAP and Miz 1 (SIZ1) is the major SUMO conjugation enhancer in response to stress, and is implicated in several aspects of plant development. Here we report that known SUMO targets are over-represented in multiple carbohydrate-related proteins, suggesting a functional link between sumoylation and sugar metabolism and signaling in plants. We subsequently observed that SUMO-conjugated proteins accumulate in response to high doses of sugar in a SIZ1-dependent manner, and that the null siz1 mutant displays increased expression of sucrose and starch catabolic genes and shows reduced starch levels. We demonstrated that SIZ1 controls germination time and post-germination growth via osmotic and sugar-dependent signaling, respectively. Glucose was specifically linked to SUMO-sugar interplay, with high levels inducing root growth inhibition and aberrant root hair morphology in siz1. The use of sugar analogs and sugar marker gene expression analysis allowed us to implicate SIZ1 in a signaling pathway dependent on glucose metabolism, probably involving modulation of SNF1-related kinase 1 (SnRK1) activity. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Adaptive gain and filtering circuit for a sound reproduction system

NASA Technical Reports Server (NTRS)

Engebretson, A. Maynard (Inventor); O'Connell, Michael P. (Inventor)

1998-01-01

Adaptive compressive gain and level dependent spectral shaping circuitry for a hearing aid include a microphone to produce an input signal and a plurality of channels connected to a common circuit output. Each channel has a preset frequency response. Each channel includes a filter with a preset frequency response to receive the input signal and to produce a filtered signal, a channel amplifier to amplify the filtered signal to produce a channel output signal, a threshold register to establish a channel threshold level, and a gain circuit. The gain circuit increases the gain of the channel amplifier when the channel output signal falls below the channel threshold level and decreases the gain of the channel amplifier when the channel output signal rises above the channel threshold level. A transducer produces sound in response to the signal passed by the common circuit output.

Effect of hypothyroidism on the purinergic responses of corpus cavernosal smooth muscle in rabbits.

PubMed

Yildirim, M K; Bagcivan, I; Sarac, B; Kilicarslan, H; Yildirim, S; Kaya, T

2008-01-01

Several studies have reported evidence of hormonal abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. In the present study, we examined purinergic relaxation responses in hypothyroidism in an experimental rabbit model and compared them with controls to evaluate the possible involvement of the purinergic pathway. The study comprised 20 male New Zealand white rabbits. The rabbits were divided into two equal groups. We tested the effects of ATP, alpha beta ATP, and adenosine precontracted with phenylephrine on the isolated corpus cavernosum preparations from control and hypothyroid rabbits. We also evaluated the effects of ATP, alpha beta ATP, and adenosine on the cGMP levels in the isolated corpus cavernosum preparations from control and hypothyroid rabbits. T3, T4, and testosterone levels were significantly lower in hypothyroid rabbits. ATP, alpha beta ATP, carbachol, and electrical field stimulation (EFS)-induced frequency-dependent relaxation responses in the isolated rabbit corpus cavernosum strips precontracted with phenylephrine reduced significantly (P<0.05). Adenosine-induced relaxation responses did not change significantly in hypothyroid rabbits. Reduction of relaxation response in hypothyroid rabbits corpus cavernosum can depend on a decreased release of nitric oxide (NO) from nitrergic nerves and endothelium.

Dietary cod-liver oil improves endothelium-dependent responses in hypercholesterolemic and atherosclerotic porcine coronary arteries.

PubMed

Shimokawa, H; Vanhoutte, P M

1988-12-01

This study examined the effects of dietary supplementation with cod-liver oil on impaired endothelium-dependent relaxations in hypercholesterolemia and in atherosclerosis in porcine coronary arteries. Sixteen male Yorkshire pigs underwent balloon endothelium removal of the left coronary arteries and were fed a 2% high-cholesterol diet for 10 weeks, with or without dietary supplementation of cod-liver oil (30 ml/day) (oil-fed and cholesterol-fed groups, respectively). This model allowed the simultaneous examination of the effects of dietary cod-liver oil on vascular reactivity in hypercholesterolemia alone (right coronary artery) and in atherosclerosis (left coronary artery). After 10 weeks of feeding, the dietary treatment with cod-liver oil caused an increase in plasma levels of eicosapentaenoic acid and a decrease in the plasma levels of arachidonic acid, whereas the treatment had no significant effect on the increases in plasma lipid levels induced by the high-cholesterol feeding. Morphometric analysis showed significant inhibition of coronary atherosclerosis by the treatment. Endothelium-dependent responses were examined in vitro in ring preparations and in bioassay experiments. Endothelium-dependent relaxations to bradykinin, serotonin, and adenosine 5'-diphosphate were larger in both right and left coronary arteries from oil-fed than from cholesterol-fed animals. Aggregating platelets from cholesterol-fed and oil-fed pigs induced comparable, larger endothelium-dependent relaxations in rings from oil-fed than from cholesterol-fed pigs. The contractions induced by serotonin or aggregating platelets were significantly inhibited in rings with endothelium from oil-fed pigs, whereas they were comparable in rings without endothelium in both groups. Relaxations to sodium nitroprusside and contractions to potassium chloride or serotonin were comparable in rings without endothelium in both groups. The bioassay experiments revealed that the release of endothelium-derived relaxing factor in response to bradykinin and the relaxations of vascular smooth muscle to the endothelial factor were greater after the fish-oil diet. These results indicate that dietary supplementation of cod-liver oil delays the impairment of endothelium-dependent relaxations in hypercholesterolemia and in atherosclerosis, partly because of an improved release of endothelium-derived relaxing factor and partly because of an improved relaxation of coronary smooth muscle to the factor.

Stimulatory Effect of Insulin on 5α-Reductase Type 1 (SRD5A1) Expression through an Akt-Dependent Pathway in Ovarian Granulosa Cells

PubMed Central

Kayampilly, Pradeep P.; Wanamaker, Brett L.; Stewart, James A.; Wagner, Carrie L.; Menon, K. M. J.

2010-01-01

Elevated levels of 5α-reduced androgens have been shown to be associated with hyperandrogenism and hyperinsulinemia, the leading causes of ovulatory dysfunction in women. 5α-Dihydrotestosterone reduces ovarian granulosa cell proliferation by inhibiting FSH-mediated mitogenic signaling pathways. The present study examined the effect of insulin on 5α-reductase, the enzyme that catalyses the conversion of androgens to their 5α-derivatives. Granulosa cells isolated from immature rat ovaries were cultured in serum-free, phenol red-free DMEM-F12 media and treated with different doses of insulin (0, 0.1, 1.0, and 10.0 μg/ml) for different time intervals up to 12 h. The expression of 5α-reductase type 1 mRNA, the predominant isoform found in granulosa cells, showed a significant (P < 0.05) increase in response to the insulin treatment up to 12 h compared with control. The catalytic activity of 5α-reductase enzyme was also stimulated in a dose-depended manner (P < 0.05). Inhibiting the Akt-dependent signaling pathway abolished the insulin-mediated increase in 5α-reductase mRNA expression, whereas inhibition of the ERK-dependent pathway had no effect. The dose-dependent increase in 5α-reductase mRNA expression as well as catalytic activity seen in response to insulin treatment was also demonstrated in the human granulosa cell line (KGN). In addition to increased mRNA expression, a dose-dependent increase in 5α-reductase protein expression in response to insulin was also seen in KGN cells, which corroborated well with that of mRNA expression. These results suggest that elevated levels of 5α-reduced androgens seen in hyperinsulinemic conditions might be explained on the basis of a stimulatory effect of insulin on 5α-reductase in granulosa cells. The elevated levels of these metabolites, in turn, might adversely affect growth and proliferation of granulosa cells, thereby impairing follicle growth and ovulation. PMID:20810561

Polarization Sensitive QWIP Thermal Imager

DTIC Science & Technology

2000-03-01

array (FPA) with peak responsivity in the long-wave infrared ( LWIR ) spectral band near 9 µm. Polarization-dependent responsivity is achieved by...demonstrated in various combinations: MWIR/ LWIR (using rectangular grid gratings), MWIR/MWIR, and LWIR / LWIR . The FPA described here was fabricated with a...CCA supports the nonuniformity correction, global gain and level control, failed pixel substitution, dynamic range reduction, BIT status and serial

Roles, Responsibilities, and Relationships among Older Husbands Caring for Wives with Progressive Dementia and Other Chronic Conditions

ERIC Educational Resources Information Center

Sanders, Sara; Power, James

2009-01-01

Men are playing greater roles in the provision of care for older adults with chronic health conditions. Husbands, in particular, encounter many role transformations as they witness their wives grow in levels of dependence as a result of their illnesses. This qualitative study examines the changes that occurred in the roles, responsibilities, and…

Bimodal regulation of p21waf1 protein as function of DNA damage levels

PubMed Central

Buscemi, G; Ricci, C; Zannini, L; Fontanella, E; Plevani, P; Delia, D

2014-01-01

Human p21Waf1 protein is well known for being transcriptionally induced by p53 and activating the cell cycle checkpoint arrest in response to DNA breaks. Here we report that p21Waf1 protein undergoes a bimodal regulation, being upregulated in response to low doses of DNA damage but rapidly and transiently degraded in response to high doses of DNA lesions. Responsible for this degradation is the checkpoint kinase Chk1, which phosphorylates p21Waf1 on T145 and S146 residues and induces its proteasome-dependent proteolysis. The initial p21Waf1 degradation is then counteracted by the ATM-Chk2 pathway, which promotes the p53-dependent accumulation of p21Waf1 at any dose of damage. We also found that p21Waf1 ablation favors the activation of an apoptotic program to eliminate otherwise irreparable cells. These findings support a model in which in human cells a balance between ATM-Chk2-p53 and the ATR-Chk1 pathways modulates p21Waf1 protein levels in relation to cytostatic and cytotoxic doses of DNA damage. PMID:25486478

Brief Report: CD14brightCD16- monocytes and sCD14 level negatively associate with CD4-memory T-cell frequency and predict HCV-decline on therapy.

PubMed

Judge, Chelsey J; Sandberg, Johan K; Funderburg, Nicholas T; Sherman, Kenneth E; Butt, Adeel A; Kang, Minhee; Landay, Alan L; Lederman, Michael M; Anthony, Donald D

2016-11-01

During HIV+ hepatitis C virus (HCV)+ coinfection CD14CD16 monocytes produce soluble immune-activation markers that predict disease progression and poor response to interferon (IFN)-α treatment. We evaluated relationships among immune activation, monocyte phenotype, CD4-memory T cells, and HCV-, cytomegalovirus-, and cytomegalovirus/Epstein-Barr virus/influenza-specific IFN-γ-response before and during IFN-α treatment. Effector-memory and central-memory CD4 T-cell frequencies were lower in HCV+ HIV+ donors than in uninfected donors and correlated negatively with HCV level, CD14CD16 monocytes, and plasma sCD14. sCD14 and CD14CD16 monocytes negatively correlated with IFN-α-dependent HCV decline. CD4 effector-memory T cells positively associated with cytomegalovirus/Epstein-Barr virus/influenza(CEF)-specific IFN-γ response, while sCD14 negatively associated with both CD4 effector-memory T cells and CEF-specific IFN-γ response. These data support a role for memory-CD4 T cells in HCV containment and link immune activation and CD14CD16-monocyte frequency to the failure of IFN-dependent HCV clearance.

Systems analysis of the single photon response in invertebrate photoreceptors.

PubMed

Pumir, Alain; Graves, Jennifer; Ranganathan, Rama; Shraiman, Boris I

2008-07-29

Photoreceptors of Drosophila compound eye employ a G protein-mediated signaling pathway that transduces single photons into transient electrical responses called "quantum bumps" (QB). Although most of the molecular components of this pathway are already known, the system-level understanding of the mechanism of QB generation has remained elusive. Here, we present a quantitative model explaining how QBs emerge from stochastic nonlinear dynamics of the signaling cascade. The model shows that the cascade acts as an "integrate and fire" device and explains how photoreceptors achieve reliable responses to light although keeping low background in the dark. The model predicts the nontrivial behavior of mutants that enhance or suppress signaling and explains the dependence on external calcium, which controls feedback regulation. The results provide insight into physiological questions such as single-photon response efficiency and the adaptation of response to high incident-light level. The system-level analysis enabled by modeling phototransduction provides a foundation for understanding G protein signaling pathways less amenable to quantitative approaches.

Quantitative analysis reveals crosstalk mechanisms of heat shock-induced attenuation of NF-κB signaling at the single cell level.

PubMed

Kardyńska, Małgorzata; Paszek, Anna; Śmieja, Jarosław; Spiller, David; Widłak, Wiesława; White, Michael R H; Paszek, Pawel; Kimmel, Marek

2018-04-01

Elevated temperature induces the heat shock (HS) response, which modulates cell proliferation, apoptosis, the immune and inflammatory responses. However, specific mechanisms linking the HS response pathways to major cellular signaling systems are not fully understood. Here we used integrated computational and experimental approaches to quantitatively analyze the crosstalk mechanisms between the HS-response and a master regulator of inflammation, cell proliferation, and apoptosis the Nuclear Factor κB (NF-κB) system. We found that populations of human osteosarcoma cells, exposed to a clinically relevant 43°C HS had an attenuated NF-κB p65 response to Tumor Necrosis Factor α (TNFα) treatment. The degree of inhibition of the NF-κB response depended on the HS exposure time. Mathematical modeling of single cells indicated that individual crosstalk mechanisms differentially encode HS-mediated NF-κB responses while being consistent with the observed population-level responses. In particular "all-or-nothing" encoding mechanisms were involved in the HS-dependent regulation of the IKK activity and IκBα phosphorylation, while others involving transport were "analogue". In order to discriminate between these mechanisms, we used live-cell imaging of nuclear translocations of the NF-κB p65 subunit. The single cell responses exhibited "all-or-nothing" encoding. While most cells did not respond to TNFα stimulation after a 60 min HS, 27% showed responses similar to those not receiving HS. We further demonstrated experimentally and theoretically that the predicted inhibition of IKK activity was consistent with the observed HS-dependent depletion of the IKKα and IKKβ subunits in whole cell lysates. However, a combination of "all-or-nothing" crosstalk mechanisms was required to completely recapitulate the single cell data. We postulate therefore that the heterogeneity of the single cell responses might be explained by the cell-intrinsic variability of HS-modulated IKK signaling. In summary, we show that high temperature modulates NF-κB responses in single cells in a complex and unintuitive manner, which needs to be considered in hyperthermia-based treatment strategies.

Ethylene Plays Multiple Nonprimary Roles in Modulating the Gravitropic Response in Tomato1

PubMed Central

Madlung, Andreas; Behringer, Friedrich J.; Lomax, Terri L.

1999-01-01

Ethylene is known to interact with auxin in regulating stem growth, and yet evidence for the role of ethylene in tropic responses is contradictory. Our analysis of four mutants of tomato (Lycopersicon esculentum) altered in their response to gravity, auxin, and/or ethylene revealed concentration-dependent modulation of shoot gravitropism by ethylene. Ethylene inhibitors reduce wild-type gravicurvature, and extremely low (0.0005–0.001 μL L−1) ethylene concentrations can restore the reduced gravitropic response of the auxin-resistant dgt (diageotropica) mutant to wild-type levels. Slightly higher concentrations of ethylene inhibit the gravitropic response of all but the ethylene-insensitive nr (never-ripe) mutant. The gravitropic responses of nr and the constitutive-response mutant epi (epinastic) are slightly and significantly delayed, respectively, but otherwise normal. The reversal of shoot gravicurvature by red light in the lz-2(lazy-2) mutant is not affected by ethylene. Taken together, these data indicate that, although ethylene does not play a primary role in the gravitropic response of tomato, low levels of ethylene are necessary for a full gravitropic response, and moderate levels of the hormone specifically inhibit gravicurvature in a manner different from ethylene inhibition of overall growth. PMID:10398726

Ethylene plays multiple nonprimary roles in modulating the gravitropic response in tomato

NASA Technical Reports Server (NTRS)

Madlung, A.; Behringer, F. J.; Lomax, T. L.; Davies, E. (Principal Investigator)

1999-01-01

Ethylene is known to interact with auxin in regulating stem growth, and yet evidence for the role of ethylene in tropic responses is contradictory. Our analysis of four mutants of tomato (Lycopersicon esculentum) altered in their response to gravity, auxin, and/or ethylene revealed concentration-dependent modulation of shoot gravitropism by ethylene. Ethylene inhibitors reduce wild-type gravicurvature, and extremely low (0.0005-0.001 microliter L-1) ethylene concentrations can restore the reduced gravitropic response of the auxin-resistant dgt (diageotropica) mutant to wild-type levels. Slightly higher concentrations of ethylene inhibit the gravitropic response of all but the ethylene-insensitive nr (never-ripe) mutant. The gravitropic responses of nr and the constitutive-response mutant epi (epinastic) are slightly and significantly delayed, respectively, but otherwise normal. The reversal of shoot gravicurvature by red light in the lz-2 (lazy-2) mutant is not affected by ethylene. Taken together, these data indicate that, although ethylene does not play a primary role in the gravitropic response of tomato, low levels of ethylene are necessary for a full gravitropic response, and moderate levels of the hormone specifically inhibit gravicurvature in a manner different from ethylene inhibition of overall growth.

Light-mediated control of DNA transcription in yeast

PubMed Central

Hughes, Robert M.; Bolger, Steven; Tapadia, Hersh; Tucker, Chandra L.

2012-01-01

A variety of methods exist for inducible control of DNA transcription in yeast. These include the use of native yeast promoters or regulatory elements that are responsive to small molecules such as galactose, methionine, and copper, or engineered systems that allow regulation by orthogonal small molecules such as estrogen. While chemically regulated systems are easy to use and can yield high levels of protein expression, they often provide imprecise control over protein levels. Moreover, chemically regulated systems can affect many other proteins and pathways in yeast, activating signaling pathways or physiological responses. Here, we describe several methods for light mediated control of DNA transcription in vivo in yeast. We describe methodology for using a red light and phytochrome dependent system to induce transcription of genes under GAL1 promoter control, as well as blue light / cryptochrome dependent systems to control transcription of genes under GAL1 promoter or LexA operator control. Light is dose dependent, inexpensive to apply, easily delivered, and does not interfere with cellular pathways, and thus has significant advantages over chemical systems. PMID:22922268

Notch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6

PubMed Central

Mouillesseaux, Kevin P.; Wiley, David S.; Saunders, Lauren M.; Wylie, Lyndsay A.; Kushner, Erich J.; Chong, Diana C.; Citrin, Kathryn M.; Barber, Andrew T.; Park, Youngsook; Kim, Jun-Dae; Samsa, Leigh Ann; Kim, Jongmin; Liu, Jiandong; Jin, Suk-Won; Bautch, Victoria L.

2016-01-01

Functional blood vessel growth depends on generation of distinct but coordinated responses from endothelial cells. Bone morphogenetic proteins (BMP), part of the TGFβ superfamily, bind receptors to induce phosphorylation and nuclear translocation of SMAD transcription factors (R-SMAD1/5/8) and regulate vessel growth. However, SMAD1/5/8 signalling results in both pro- and anti-angiogenic outputs, highlighting a poor understanding of the complexities of BMP signalling in the vasculature. Here we show that BMP6 and BMP2 ligands are pro-angiogenic in vitro and in vivo, and that lateral vessel branching requires threshold levels of R-SMAD phosphorylation. Endothelial cell responsiveness to these pro-angiogenic BMP ligands is regulated by Notch status and Notch sets responsiveness by regulating a cell-intrinsic BMP inhibitor, SMAD6, which affects BMP responses upstream of target gene expression. Thus, we reveal a paradigm for Notch-dependent regulation of angiogenesis: Notch regulates SMAD6 expression to affect BMP responsiveness of endothelial cells and new vessel branch formation. PMID:27834400

Esculin improves dyslipidemia, inflammation and renal damage in streptozotocin-induced diabetic rats.

PubMed

Wang, Yue-Hua; Liu, Yan-Hong; He, Guo-Rong; Lv, Yang; Du, Guan-Hua

2015-11-09

Increasing studies have shown that dyslipidemia and inflammatory responses play important roles in the progression of microvascular diabetic complications. Esculin (ES), a coumarin derivative, was extracted from Fraxinus rhynchophylla. The present study was to evaluate the potential effects of ES on lipid metabolism, inflammation responses and renal damage in streptozotocin (STZ)-induced experimental diabetic rats and explore the possible mechanism. Diabetic rat model was established by administration high-glucose-fat diet and intraperitoneal injection of STZ 45 mg/kg. ES was administrated to diabetic rats intragastrically at 10, 30 and 90 mg/kg for 10 weeks respectively. The levels of triglycerides (TG), total cholesterol (T-CHO), low density lipoproteins (LDL), and high-density-cholesterol (HDL-C) in serum were measured. IL-1, IL-6, ICAM-1, NO, NAGL, and AGEs level in serum were detected by ELISA assay. The accumulation of AGEs in kidney tissue was examined by immunohistochemistry assay. The results showed that ES could decrease TG, T-CHO, LDL levels in serum of diabetic rats in a dose dependent manner. ES also decreased IL-1, IL-6, ICAM-1, NO and NGAL levels in serum of diabetic rats in a dose dependent manner. Furthermore, ES at 30 and 90 mg/kg significantly decreased AGEs level in serum and alleviated AGEs accumulation in renal in diabetic rats. Our findings indicate that ES could improve dyslipidemia, inflammation responses, renal damage in STZ-induced diabetic rats and the possible mechanism might be associated with the inhibition of AGEs formation.

Effect of Human Auditory Efferent Feedback on Cochlear Gain and Compression

PubMed Central

Drga, Vit; Plack, Christopher J.

2014-01-01

The mammalian auditory system includes a brainstem-mediated efferent pathway from the superior olivary complex by way of the medial olivocochlear system, which reduces the cochlear response to sound (Warr and Guinan, 1979; Liberman et al., 1996). The human medial olivocochlear response has an onset delay of between 25 and 40 ms and rise and decay constants in the region of 280 and 160 ms, respectively (Backus and Guinan, 2006). Physiological studies with nonhuman mammals indicate that onset and decay characteristics of efferent activation are dependent on the temporal and level characteristics of the auditory stimulus (Bacon and Smith, 1991; Guinan and Stankovic, 1996). This study uses a novel psychoacoustical masking technique using a precursor sound to obtain a measure of the efferent effect in humans. This technique avoids confounds currently associated with other psychoacoustical measures. Both temporal and level dependency of the efferent effect was measured, providing a comprehensive measure of the effect of human auditory efferents on cochlear gain and compression. Results indicate that a precursor (>20 dB SPL) induced efferent activation, resulting in a decrease in both maximum gain and maximum compression, with linearization of the compressive function for input sound levels between 50 and 70 dB SPL. Estimated gain decreased as precursor level increased, and increased as the silent interval between the precursor and combined masker-signal stimulus increased, consistent with a decay of the efferent effect. Human auditory efferent activation linearizes the cochlear response for mid-level sounds while reducing maximum gain. PMID:25392499

Density dependence governs when population responses to multiple stressors are magnified or mitigated.

PubMed

Hodgson, Emma E; Essington, Timothy E; Halpern, Benjamin S

2017-10-01

Population endangerment typically arises from multiple, potentially interacting anthropogenic stressors. Extensive research has investigated the consequences of multiple stressors on organisms, frequently focusing on individual life stages. Less is known about population-level consequences of exposure to multiple stressors, especially when exposure varies through life. We provide the first theoretical basis for identifying species at risk of magnified effects from multiple stressors across life history. By applying a population modeling framework, we reveal conditions under which population responses from stressors applied to distinct life stages are either magnified (synergistic) or mitigated. We find that magnification or mitigation critically depends on the shape of density dependence, but not the life stage in which it occurs. Stressors are always magnified when density dependence is linear or concave, and magnified or mitigated when it is convex. Using Bayesian numerical methods, we estimated the shape of density dependence for eight species across diverse taxa, finding support for all three shapes. © 2017 by the Ecological Society of America.

Lucigenin-dependent chemiluminescence in articular chondrocytes.

PubMed

Rathakrishnan, C; Tiku, M L

1993-08-01

We were recently able to measure intracellular levels of hydrogen peroxide within normal articular chondrocytes using the trapped indicator 2',7'-dichlorofluorescein diacetate. Further studies have shown that stimulated chondrocytes produce luminol-dependent chemiluminescence, suggesting that these cells produce hydrogen peroxide and singlet oxygen. In the present study, we have investigated the lucigenin-dependent chemiluminescence response in normal articular chondrocytes. Chondrocytes either in suspension or adhered to cover slips showed lucigenin-dependent chemiluminescence. There was a dose-dependent increase in chemiluminescence response when chondrocytes were incubated with soluble stimuli like phorbol-myristate-acetate, concanavalin A, and f-met-leu-phe. Catalase and the metabolic inhibitor, sodium azide, which inhibits the enzyme myeloperoxidase, had no inhibitory effect on lucigenin-dependent chemiluminescence production. Only the antioxidant, superoxide dismutase, prevented lucigenin-dependent chemiluminescence, indicating that this assay measures the production of superoxide anions by chondrocytes. We confirmed that chondrocytes release superoxide radicals using the biochemical assay of ferricytochrome c reduction. Since cartilage tissue is semi-transparent, we were able to measure chemiluminescence response in live cartilage tissue, showing that chondrocytes which are embedded within the matrix can also generate superoxide anion radicals. Reactive oxygen intermediates have been shown to play a significant role in the degradation of matrix in arthritis. Our previous and present studies suggest that oxygen radicals produced by chondrocytes may be an important mechanism by which chondrocytes induce cartilage matrix degradation.

Climatic Stress during Stand Development Alters the Sign and Magnitude of Age-Related Growth Responses in a Subtropical Mountain Pine.

PubMed

Ruiz-Benito, Paloma; Madrigal-González, Jaime; Young, Sarah; Mercatoris, Pierre; Cavin, Liam; Huang, Tsurng-Juhn; Chen, Jan-Chang; Jump, Alistair S

2015-01-01

The modification of typical age-related growth by environmental changes is poorly understood, In part because there is a lack of consensus at individual tree level regarding age-dependent growth responses to climate warming as stands develop. To increase our current understanding about how multiple drivers of environmental change can modify growth responses as trees age we used tree ring data of a mountain subtropical pine species along an altitudinal gradient covering more than 2,200 m of altitude. We applied mixed-linear models to determine how absolute and relative age-dependent growth varies depending on stand development; and to quantify the relative importance of tree age and climate on individual tree growth responses. Tree age was the most important factor for tree growth in models parameterised using data from all forest developmental stages. Contrastingly, the relationship found between tree age and growth became non-significant in models parameterised using data corresponding to mature stages. These results suggest that although absolute tree growth can continuously increase along tree size when trees reach maturity age had no effect on growth. Tree growth was strongly reduced under increased annual temperature, leading to more constant age-related growth responses. Furthermore, young trees were the most sensitive to reductions in relative growth rates, but absolute growth was strongly reduced under increased temperature in old trees. Our results help to reconcile previous contrasting findings of age-related growth responses at the individual tree level, suggesting that the sign and magnitude of age-related growth responses vary with stand development. The different responses found to climate for absolute and relative growth rates suggest that young trees are particularly vulnerable under warming climate, but reduced absolute growth in old trees could alter the species' potential as a carbon sink in the future.

TLR8-driven IL-12-dependent reciprocal and synergistic activation of NK cells and monocytes by immunostimulatory RNA.

PubMed

Berger, Michael; Ablasser, Andrea; Kim, Sarah; Bekeredjian-Ding, Isabelle; Giese, Thomas; Endres, Stefan; Hornung, Veit; Hartmann, Gunther

2009-04-01

Immunostimulatory RNA (isRNA) depending on sequence and structure can function as a ligand for Toll-like receptor (TLR) 7 and TLR8. Here we show that isRNA induces high levels of bioactive interleukin-12 in purified human monocytes, whereas purified natural killer (NK) cells did not respond. However, in a coculture of monocytes and NK cells, isRNA dramatically increased NK cell function. Activation of monocytes and NK cells was bidirectional, as monocytes in the presence of NK cells produced higher levels of bioactive interleukin-12. As a result of the monocyte-NK cell interaction in peripheral blood mononuclear cells isRNA induced high levels of interferon (IFN)-gamma in NK cells and strong NK cell-mediated cytotoxic activity. Induction of simultaneous IFN-gamma production and lytic activity by isRNA in NK cells was higher as compared with other established nucleic acid or small molecule TLR ligands. Our studies demonstrate that monocytes play a pivotal role in the orchestration of a strong NK cell response. With early NK cell-dependent IFN-gamma production being critical for the development of antigen-specific cytotoxic T lymphocyte responses, newly developed isRNA-based TLR8 ligands join the list of promising oligonucleotides for immunotherapy of viral infection and cancer.

Potentiation of lymphocyte proliferative responses by nickel sulfide

NASA Technical Reports Server (NTRS)

Jaramillo, A.; Sonnenfeld, G.

1992-01-01

Crystalline nickel sulfide (NiS) induced a spleen cell proliferation that resembles a mixed lymphocyte reaction (MLR). It depended on cell-cell interaction, induced high levels of interleukin-1 (IL-1) and interleukin-2 (IL-2) and the responding cell subpopulation was composed of CD4+ T lymphocytes. Furthermore, the proliferation was inhibited in a dose-dependent manner by magnesium. Crystalline NiS also increased significantly the spleen cell proliferative response to concanavalin A (Con A) and lipopolysaccharide (LPS) with magnesium potentiating the combined effects of crystalline NiS and mitogens. Interestingly, crystalline NiS did not show any effect on the induction of IL-2 by Con A. The results described herein suggest that crystalline NiS can potentiate both antigenic (MLR) and mitogenic (Con A and LPS) proliferative responses in vitro. Crystalline NiS appears to potentiate these responses by acting in the form of ionic nickel on several intracellular targets for which magnesium ions have different noncompetitive interactions. The effects of magnesium on the potentiating action of crystalline NiS are different depending upon the type of primary stimulatory signal for proliferation (mitogenic or antigenic).

The influence of SV40 immortalization of human fibroblasts on p53-dependent radiation responses

NASA Technical Reports Server (NTRS)

Kohli, M.; Jorgensen, T. J.

1999-01-01

The simian virus 40 large tumor antigen (SV40 Tag) has been ascribed many functions critical to viral propagation, including binding to the mammalian tumor suppressor p53. Recent studies have demonstrated that SV40-transformed murine cells have functional p53. The status of p53 in SV40-immortalized human cells, however, has not been characterized. We have found that in response to ionizing radiation, p53-dependent p21 transactivation activity is present, albeit reduced, in SV40-immortalized cells and that this activity can be further reduced with either dominant negative p53 expression or higher SV40 Tag expression. Furthermore, overexpression of p53 in SV40-immortalized ataxia-telangiectasia (A-T) cells restores p53-dependent p21 induction to typical A-T levels. All SV40-immortalized cell lines exhibited an absence of G1 arrest. Moreover, all SV40-immortalized cell lines exhibited increased apoptosis relative to primary cells in response to ionizing radiation, suggesting that SV40 immortalization results in a unique phenotype with regard to DNA damage responses. Copyright 1999 Academic Press.

Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity

PubMed Central

Walter, Marc; Gerber, Hana; Seifritz, Erich; Brenneisen, Rudolf; Wiesbeck, Gerhard A.; Riecher-Rössler, Anita; Lang, Undine E.; Borgwardt, Stefan

2015-01-01

Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of amygdala-related connectivity during fear processing may provide a prognostic tool to assess stress levels in heroin-dependent patients and to quantify the efficacy of maintenance treatments in drug addiction. PMID:25414039

A cell impedance measurement device for the cytotoxicity assay dependent on the velocity of supplied toxic fluid

NASA Astrophysics Data System (ADS)

Kang, Yoon-Tae; Kim, Min-Ji; Cho, Young-Ho

2018-04-01

We present a cell impedance measurement chip capable of characterizing the toxic response of cells depending on the velocity of the supplied toxic fluid. Previous impedance-based devices using a single open-top chamber have been limited to maintaining a constant supply velocity, and devices with a single closed-top chamber present difficulties in simultaneous cytotoxicity assay for varying levels of supply velocities. The present device, capable of generating constant and multiple levels of toxic fluid velocity simultaneously within a single stepwise microchannel, performs a cytotoxicity assay dependent on toxic fluid velocity, in order to find the effective velocity of toxic fluid to cells for maximizing the cytotoxic effect. We analyze the cellular toxic response of 5% ethanol media supplied to cancer cells within a toxic fluid velocity range of 0-8.3 mm s-1. We observe the velocity-dependent cell detachment rate, impedance, and death rate. We find that the cell detachment rate decreased suddenly to 2.4% at a velocity of 4.4 mm s-1, and that the change rates of cell resistance and cell capacitance showed steep decreases to 8% and 41%, respectively, at a velocity of 5.7 mm s-1. The cell death rate and impedance fell steeply to 32% at a velocity of 5.7 mm s-1. We conclude that: (1) the present device is useful in deciding on the toxic fluid velocity effective to cytotoxicity assay, since the cellular toxic response is dependent on the velocity of toxic fluid, and; (2) the cell impedance analysis facilitates a finer cellular response analysis, showing better correlation with the cell death rate, compared to conventional visual observation. The present device, capable of performing the combinational analysis of toxic fluid velocity and cell impedance, has potential for application to the fine cellular toxicity assay of drugs with proper toxic fluid velocity.

Extinction of avoidance behavior by safety learning depends on endocannabinoid signaling in the hippocampus.

PubMed

Micale, Vincenzo; Stepan, Jens; Jurik, Angela; Pamplona, Fabricio A; Marsch, Rudolph; Drago, Filippo; Eder, Matthias; Wotjak, Carsten T

2017-07-01

The development of exaggerated avoidance behavior is largely responsible for the decreased quality of life in patients suffering from anxiety disorders. Studies using animal models have contributed to the understanding of the neural mechanisms underlying the acquisition of avoidance responses. However, much less is known about its extinction. Here we provide evidence in mice that learning about the safety of an environment (i.e., safety learning) rather than repeated execution of the avoided response in absence of negative consequences (i.e., response extinction) allowed the animals to overcome their avoidance behavior in a step-down avoidance task. This process was context-dependent and could be blocked by pharmacological (3 mg/kg, s.c.; SR141716) or genetic (lack of cannabinoid CB1 receptors in neurons expressing dopamine D1 receptors) inactivation of CB1 receptors. In turn, the endocannabinoid reuptake inhibitor AM404 (3 mg/kg, i.p.) facilitated safety learning in a CB1-dependent manner and attenuated the relapse of avoidance behavior 28 days after conditioning. Safety learning crucially depended on endocannabinoid signaling at level of the hippocampus, since intrahippocampal SR141716 treatment impaired, whereas AM404 facilitated safety learning. Other than AM404, treatment with diazepam (1 mg/kg, i.p.) impaired safety learning. Drug effects on behavior were directly mirrored by drug effects on evoked activity propagation through the hippocampal trisynaptic circuit in brain slices: As revealed by voltage-sensitive dye imaging, diazepam impaired whereas AM404 facilitated activity propagation to CA1 in a CB1-dependent manner. In line with this, systemic AM404 enhanced safety learning-induced expression of Egr1 at level of CA1. Together, our data render it likely that AM404 promotes safety learning by enhancing information flow through the trisynaptic circuit to CA1. Copyright © 2017 Elsevier Ltd. All rights reserved.

Concorde noise-induced building vibrations, Sully Plantation - Report no. 2, Chantilly, Virginia

NASA Technical Reports Server (NTRS)

1976-01-01

Noise-induced building vibrations associated with Concorde operations were studied. The approach is to record the levels of induced vibrations and associated indoor/outdoor noise levels in selected homes, historic and other buildings near Dulles International Airport. Representative data are presented which were recorded at Sully Plantation, Chantilly, Virginia during the periods of May 20 through May 28, 1976, and June 14 through June 17, 1976. Recorded data provide relationships between the vibration levels of windows, walls, floors, and the noise associated with Concorde operations, other aircraft, and nonaircraft events. The results presented are drawn from the combined May-June data base which is considerably larger than the May data base covered. The levels of window, wall and floor vibratory response resulting from Concorde operations are higher than the vibratory levels associated with conventional aircraft. Furthermore, the vibratory responses of the windows are considerably higher than those of the walls and floors. The window response is higher for aircraft than recorded nonaircraft events and exhibits a linear response relationship with the overall sound pressure level. For a given sound pressure level, the Concorde may cause more vibration than a conventional aircraft due to spectral or other differences. However, the responses associated with Concorde appear to be much more dependent upon sound pressure level than spectral or other characteristics of the noise.

Intercellular salicylic acid accumulation during compatible and incompatible Arabidopsis-Pseudomonas syringae interactions

PubMed Central

Wilson, Daniel C; Carella, Philip; Cameron, Robin K

2014-01-01

The phytohormone salicylic acid (SA) plays an important role in several disease resistance responses. During the Age-Related Resistance (ARR) response that occurs in mature Arabidopsis responding to Pseudomonas syringae pv tomato (Pst), SA accumulates in the intercellular space where it may act as an antimicrobial agent. Recently we measured intracellular and intercellular SA levels in young, ARR-incompetent plants responding to virulent and avirulent strains of Pst to determine if intercellular SA accumulation is a component of additional defense responses to Pst. In young plants virulent Pst suppressed both intra- and intercellular SA accumulation in a coronatine-dependent manner. In contrast, high levels of intra- and intercellular SA accumulated in response to avirulent Pst. Our results support the idea that SA accumulation in the intercellular space is an important component of multiple defense responses. Future research will include understanding how mature plants counteract the effects of coronatine during the ARR response. PMID:25763618

A new era for functional labeling of neurons: activity-dependent promoters have come of age

PubMed Central

Kawashima, Takashi; Okuno, Hiroyuki; Bito, Haruhiko

2014-01-01

Genetic labeling of neurons with a specific response feature is an emerging technology for precise dissection of brain circuits that are functionally heterogeneous at the single-cell level. While immediate early gene mapping has been widely used for decades to identify brain regions which are activated by external stimuli, recent characterization of the promoter and enhancer elements responsible for neuronal activity-dependent transcription have opened new avenues for live imaging of active neurons. Indeed, these advancements provided the basis for a growing repertoire of novel experiments to address the role of active neuronal networks in cognitive behaviors. In this review, we summarize the current literature on the usage and development of activity-dependent promoters and discuss the future directions of this expanding new field. PMID:24795570

Carrageenan-induced mouse paw oedema is biphasic, age-weight dependent and displays differential nitric oxide cyclooxygenase-2 expression

PubMed Central

Posadas, Inmaculada; Bucci, Mariarosaria; Roviezzo, Fiorentina; Rossi, Antonietta; Parente, Luca; Sautebin, Lidia; Cirino, Giuseppe

2004-01-01

Injection of carrageenan 1% (50 μl) in the mouse paw causes a biphasic response: an early inflammatory response that lasts 6 h and a second late response that peaks at 72 h, declining at 96 h. Only mice 7- or 8-week old, weighing 32–34 g, displayed a consistent response in both phases. In 8-week-old mice, myeloperoxidase (MPO) levels are significantly elevated in the early phase at 6 h and reach their maximum at 24 h to decline to basal value at 48 h. Nitrate+nitrite (NOx) levels in the paw are maximal after 2 h and slowly decline thereafter in contrast to prostaglandin E2 levels that peak in the second phase at the 72 h point. Western blot analysis showed that inducible nitric oxide synthase (iNOS) is detectable at 6 h and cyclooxygenase 2 (COX-2) at 24 h point, respectively. Analysis of endothelial nitric oxide synthase (eNOS), iNOS and COX-2 expression at 6 and 24 h in 3–8-week-old mice demonstrated that both eNOS and iNOS expressions are dependent upon the age–weight of mice, as opposite to COX-2 that is present only in the second phase of the oedema and is not linked to mouse age–weight. Subplantar injection of carrageenan to C57BL/6J causes a biphasic oedema that is significantly reduced by about 20% when compared to CD1 mice. Interestingly, in these mice, iNOS expression is absent up to 6 h, as opposite to CD1, and becomes detectable at the 24 h point. Cyclooxygenase (COX-1) expression is upregulated between 4 and 24 h after carrageenan injection, whereas in CD1 mice COX-1 remains unchanged after irritant agent injection. MPO levels are maximal at the 24 h point and they are significantly lower, at 6 h point, than MPO levels detected in CD1 mice. In conclusion, mouse paw oedema is biphasic and age-weight dependent. The present results are the first report on the differential expressions of eNOS, iNOS, COX-1 and COX-2 in response to carrageenan injection in the two phases of the mouse paw oedema. PMID:15155540

[Urban noise pollution].

PubMed

Chouard, C H

2001-07-01

Noise is responsible for cochlear and general damages. Hearing loss and tinnitus greatly depend on sound intensity and duration. Short-duration sound of sufficient intensity (gunshot or explosion) will not be described because they are not currently encountered in our normal urban environment. Sound levels of less than 75 d (A) are unlikely to cause permanent hearing loss, while sound levels of about 85 d (A) with exposures of 8 h per day will produce permanent hearing loss after many years. Popular and largely amplified music is today one of the most dangerous causes of noise induced hearing loss. The intensity of noises (airport, highway) responsible for stress and general consequences (cardiovascular) is generally lower. Individual noise sensibility depends on several factors. Strategies to prevent damage from sound exposure should include the use of individual hearing protection devices, education programs beginning with school-age children, consumer guidance, increased product noise labelling, and hearing conservation programs for occupational settings.

Effect of combined platinum and electron on the temperature dependence of forward voltage in fast recovery diode

NASA Astrophysics Data System (ADS)

Jia, Yun-Peng; Zhao, Bao; Yang, Fei; Wu, Yu; Zhou, Xuan; Li, Zhe; Tan, Jian

2015-12-01

The temperature dependences of forward voltage drop (VF) of the fast recovery diodes (FRDs) are remarkably influenced by different lifetime controlled treatments. In this paper the results of an experimental study are presented, which are the lifetime controls of platinum treatment, electron irradiation treatment, and the combined treatment of the above ones. Based on deep level transient spectroscopy (DLTS) measurements, a new level E6 (EC-0.376 eV) is found in the combined lifetime treated (CLT) sample, which is different from the levels of the individual platinum and electron irradiation ones. Comparing the tested VF results of CLT samples with the others, the level E6 is responsible for the degradation of temperature dependence of the forward voltage drop in the FRD. Project supported by the Doctoral Fund of Ministry of Education of China (Grant No. 20111103120016) and the State Grid Corporation of China Program of Science and Technology, China (Grant No. 5455DW140003).

Mast cell-dependent IL-33/ST2 signaling is protective against the development of airway hyperresponsiveness in a house dust mite mouse model of asthma.

PubMed

Zoltowska Nilsson, A M; Lei, Y; Adner, M; Nilsson, G P

2018-03-01

Interleukin-33 (IL-33) and its receptor ST2 have been influentially associated with the pathophysiology of asthma. Due to the divergent roles of IL-33 in regulating mast cell functions, there is a need to further characterize IL-33/ST2-dependent mast cell responses and their significance in the context of asthma. This study aimed to investigate how IL-33/ST2-dependent mast cell responses contribute to the development of airway hyperresponsiveness (AHR) and airway inflammation in a mouse model of house dust mite (HDM)-induced asthma. Mast cell-deficient C57BL/6-Kit W-sh (Wsh) mice engrafted with either wild-type (Wsh + MC-WT) or ST2-deficient bone marrow-derived mast cells (Wsh + MC-ST2KO) were exposed to HDM delivered intranasally. An exacerbated development of AHR in response to HDM was seen in Wsh + MC-ST2KO compared with Wsh + MC-WT mice. The contribution of this IL-33/ST2-dependent mast cell response to AHR seems to reside within the smaller airways in the peripheral parts of the lung, as suggested by the isolated yet marked effect on tissue resistance. Considering the absence of a parallel increase in cellular inflammation in bronchoalveolar lavage fluid (BALF) and lung, the aggravated AHR in Wsh + MC-ST2KO mice seems to be independent of cellular inflammation. We observed an association between the elevated AHR and reduced PGE 2 levels in BALF . Due to the protective properties of PGE 2 in airway responses, it is conceivable that IL-33/ST2-dependent mast cell induction of PGE 2 could be responsible for the dampening effect on AHR. In conclusion, we reveal that IL-33/ST2-dependent mast cell responses can have a protective, rather than causative role, in the development of AHR.

The effects of age and drug dependency on the emotional exhaustion and job satisfaction of adult streetworkers in australia.

PubMed

Cregan, Christina; Kulik, Carol T; Salinger, Dani

2013-07-01

This multi-method study investigated a sample of adult streetworkers (n = 107) in Melbourne, Australia in 2008. We contacted outdoor prostitutes through four "drop-in" centers run by not-for-profit organizations. Drug use was the over-riding common characteristic of most of these streetworkers. Using emotional labor theory as a theoretical framework, we hypothesized that individuals who worked on the streets solely to earn money to buy drugs would experience the highest levels of emotional exhaustion and the lowest levels of job satisfaction. We predicted these effects would be most evident for older drug dependent streetworkers. Content analysis of open-ended interview responses identified acting, age, and drug dependency as key themes. Moderator hierarchical regression analysis of responses to closed-ended questions with tests for mediation supported the hypotheses. It also demonstrated that older drug dependent streetworkers felt most trapped in their occupation and this sense of being locked-in was associated with emotional exhaustion but not with job satisfaction. The evidence that age and drug dependency affects the psychological outcomes associated with streetwork suggests that the efforts of police and the courts will be ineffective in dealing with people whose addiction traps them in an occupation that offers few intrinsic rewards. Decriminalization would encourage police to protect streetworkers from violence. Agencies could seek financial support to provide welfare and exit strategies.

ORA59 and EIN3 interaction couples jasmonate-ethylene synergistic action to antagonistic salicylic acid regulation of PDF expression.

PubMed

He, Xiang; Jiang, Jishan; Wang, Chang-Quan; Dehesh, Katayoon

2017-04-01

Hormonal crosstalk is central for tailoring plant responses to the nature of challenges encountered. The role of antagonism between the two major defense hormones, salicylic acid (SA) and jasmonic acid (JA), and modulation of this interplay by ethylene (ET) in favor of JA signaling pathway in plant stress responses is well recognized, but the underlying mechanism is not fully understood. Here, we show the opposing function of two transcription factors, ethylene insensitive3 (EIN3) and EIN3-Like1 (EIL1), in SA-mediated suppression and JA-mediated activation of PLANT DEFENSIN1.2 (PDF1.2). This functional duality is mediated via their effect on protein, not transcript levels of the PDF1.2 transcriptional activator octadecanoid-responsive Arabidopsis59 (ORA59). Specifically, JA induces ORA59 protein levels independently of EIN3/EIL1, whereas SA reduces the protein levels dependently of EIN3/EIL1. Co-infiltration assays revealed nuclear co-localization of ORA59 and EIN3, and split-luciferase together with yeast-two-hybrid assays established their physical interaction. The functional ramification of the physical interaction is EIN3-dependent degradation of ORA59 by the 26S proteasome. These findings allude to SA-responsive reduction of ORA59 levels mediated by EIN3 binding to and targeting of ORA59 for degradation, thus nominating ORA59 pool as a coordination node for the antagonistic function of ET/JA and SA. © 2017 Institute of Botany, Chinese Academy of Sciences.

Wide-dynamic-range forward suppression in marmoset inferior colliculus neurons is generated centrally and accounts for perceptual masking.

PubMed

Nelson, Paul C; Smith, Zachary M; Young, Eric D

2009-02-25

An organism's ability to detect and discriminate sensory inputs depends on the recent stimulus history. For example, perceptual detection thresholds for a brief tone can be elevated by as much as 50 dB when following a masking stimulus. Previous work suggests that such forward masking is not a direct result of peripheral neural adaptation; the central pathway apparently modifies the representation in a way that further attenuates the input's response to short probe signals. Here, we show that much of this transformation is complete by the level of the inferior colliculus (IC). Single-neuron extracellular responses were recorded in the central nucleus of the awake marmoset IC. The threshold for a 20 ms probe tone presented at best frequency was determined for various masker-probe delays, over a range of masker sound pressure levels (SPLs) and frequencies. The most striking aspect of the data was the increased potency of forward maskers as their SPL was increased, despite the fact that the excitatory response to the masker was often saturating or nonmonotonic over the same range of levels. This led to probe thresholds at high masker levels that were almost always higher than those observed in the auditory nerve. Probe threshold shifts were not usually caused by a persistent excitatory response to the masker; instead we propose a wide-dynamic-range inhibitory mechanism locked to sound offset as an explanation for several key aspects of the data. These findings further delineate the role of subcortical auditory processing in the generation of a context-dependent representation of ongoing acoustic scenes.

Cytokinin stabilizes WUSCHEL by acting on the protein domains required for nuclear enrichment and transcription.

PubMed

Snipes, Stephen A; Rodriguez, Kevin; DeVries, Aaron E; Miyawaki, Kaori N; Perales, Mariano; Xie, Mingtang; Reddy, G Venugopala

2018-04-01

Concentration-dependent transcriptional regulation and the spatial regulation of transcription factor levels are poorly studied in plant development. WUSCHEL, a stem cell-promoting homeodomain transcription factor, accumulates at a higher level in the rib meristem than in the overlying central zone, which harbors stem cells in the shoot apical meristems of Arabidopsis thaliana. The differential accumulation of WUSCHEL in adjacent cells is critical for the spatial regulation and levels of CLAVATA3, a negative regulator of WUSCHEL transcription. Earlier studies have revealed that DNA-dependent dimerization, subcellular partitioning and protein destabilization control WUSCHEL protein levels and spatial accumulation. Moreover, the destabilization of WUSCHEL may also depend on the protein concentration. However, the roles of extrinsic spatial cues in maintaining differential accumulation of WUS are not understood. Through transient manipulation of hormone levels, hormone response patterns and analysis of the receptor mutants, we show that cytokinin signaling in the rib meristem acts through the transcriptional regulatory domains, the acidic domain and the WUSCHEL-box, to stabilize the WUS protein. Furthermore, we show that the same WUSCHEL-box functions as a degron sequence in cytokinin deficient regions in the central zone, leading to the destabilization of WUSCHEL. The coupled functions of the WUSCHEL-box in nuclear retention as described earlier, together with cytokinin sensing, reinforce higher nuclear accumulation of WUSCHEL in the rib meristem. In contrast a sub-threshold level may expose the WUSCHEL-box to destabilizing signals in the central zone. Thus, the cytokinin signaling acts as an asymmetric spatial cue in stabilizing the WUSCHEL protein to lead to its differential accumulation in neighboring cells, which is critical for concentration-dependent spatial regulation of CLAVATA3 transcription and meristem maintenance. Furthermore, our work shows that cytokinin response is regulated independently of the WUSCHEL function which may provide robustness to the regulation of WUSCHEL concentration.

Quantification of airport community noise impact in terms of noise levels, population density, and human subjective response

NASA Technical Reports Server (NTRS)

Deloach, R.

1981-01-01

The Fraction Impact Method (FIM), developed by the National Research Council (NRC) for assessing the amount and physiological effect of noise, is described. Here, the number of people exposed to a given level of noise is multiplied by a weighting factor that depends on noise level. It is pointed out that the Aircraft-noise Levels and Annoyance MOdel (ALAMO), recently developed at NASA Langley Research Center, can perform the NRC fractional impact calculations for given modes of operation at any U.S. airport. The sensitivity of these calculations to errors in estimates of population, noise level, and human subjective response is discussed. It is found that a change in source noise causes a substantially smaller change in contour area than would be predicted simply on the basis of inverse square law considerations. Another finding is that the impact calculations are generally less sensitive to source noise errors than to systematic errors in population or subjective response.

Heuristics and biases: interactions among numeracy, ability, and reflectiveness predict normative responding

PubMed Central

Klaczynski, Paul A.

2014-01-01

In Stanovich's (2009a, 2011) dual-process theory, analytic processing occurs in the algorithmic and reflective minds. Thinking dispositions, indexes of reflective mind functioning, are believed to regulate operations at the algorithmic level, indexed by general cognitive ability. General limitations at the algorithmic level impose constraints on, and affect the adequacy of, specific strategies and abilities (e.g., numeracy). In a study of 216 undergraduates, the hypothesis that thinking dispositions and general ability moderate the relationship between numeracy (understanding of mathematical concepts and attention to numerical information) and normative responses on probabilistic heuristics and biases (HB) problems was tested. Although all three individual difference measures predicted normative responses, the numeracy-normative response association depended on thinking dispositions and general ability. Specifically, numeracy directly affected normative responding only at relatively high levels of thinking dispositions and general ability. At low levels of thinking dispositions, neither general ability nor numeric skills related to normative responses. Discussion focuses on the consistency of these findings with the hypothesis that the implementation of specific skills is constrained by limitations at both the reflective level and the algorithmic level, methodological limitations that prohibit definitive conclusions, and alternative explanations. PMID:25071639

Heuristics and biases: interactions among numeracy, ability, and reflectiveness predict normative responding.

PubMed

Klaczynski, Paul A

2014-01-01

In Stanovich's (2009a, 2011) dual-process theory, analytic processing occurs in the algorithmic and reflective minds. Thinking dispositions, indexes of reflective mind functioning, are believed to regulate operations at the algorithmic level, indexed by general cognitive ability. General limitations at the algorithmic level impose constraints on, and affect the adequacy of, specific strategies and abilities (e.g., numeracy). In a study of 216 undergraduates, the hypothesis that thinking dispositions and general ability moderate the relationship between numeracy (understanding of mathematical concepts and attention to numerical information) and normative responses on probabilistic heuristics and biases (HB) problems was tested. Although all three individual difference measures predicted normative responses, the numeracy-normative response association depended on thinking dispositions and general ability. Specifically, numeracy directly affected normative responding only at relatively high levels of thinking dispositions and general ability. At low levels of thinking dispositions, neither general ability nor numeric skills related to normative responses. Discussion focuses on the consistency of these findings with the hypothesis that the implementation of specific skills is constrained by limitations at both the reflective level and the algorithmic level, methodological limitations that prohibit definitive conclusions, and alternative explanations.

Ott1 (Rbm15) regulates thrombopoietin response in hematopoietic stem cells through alternative splicing of c-Mpl

PubMed Central

Xiao, Nan; Laha, Suparna; Das, Shankar P.; Morlock, Kayla; Jesneck, Jonathan L.

2015-01-01

Thrombopoietin (Thpo) signaling through the c-Mpl receptor promotes either quiescence or proliferation of hematopoietic stem cells (HSCs) in a concentration-dependent manner; however, in vivo Thpo serum levels are responsive to platelet mass rather than HSC demands, suggesting additional regulation exists. Ott1 (Rbm15), a spliceosomal component originally identified as a fusion partner in t(1;22)-associated acute megakaryocytic leukemia, is also essential for maintaining HSC quiescence under stress. Ott1 controls the alternative splicing of a dominant negative isoform, Mpl-TR, capable of inhibiting HSC engraftment and attenuating Thpo signaling. Ott1, which associates with Hdac3 and the histone methyltransferase, Setd1b, binds to both c-Mpl RNA and chromatin and regulates H4 acetylation and H3K4me3 marks. Histone deacetylase or histone methyltransferase inhibition also increases Mpl-TR levels, suggesting that Ott1 uses an underlying epigenetic mechanism to control alternative splicing of c-Mpl. Manipulation of Ott1-dependent alternative splicing may therefore provide a novel pharmacologic avenue for regulating HSC quiescence and proliferation in response to Thpo. PMID:25468569

Adjuvant dependence of APS pathology-related low-affinity antibodies during secondary immune response to tetanus toxoid in BALB/c mice.

PubMed

Zivković, Irena; Petrušić, Vladimir; Dimitrijević, Rajna; Stojanović, Marijana; Dimitrijević, Ljiljana

2013-05-01

One of the established animal models for autoimmune disease antiphospholipid syndrome (APS) is TTd hyperimmunization of mice. Tetanus toxoid (TTd) and plasma protein β2GPI share structural homology so that immunization with TTd induces appearance of cross-reactive antibodies. In this paper, we have investigated the presence and dynamic of fluctuation of specific (anti-TTd) and auto (anti-β2GPI) antibodies induced in BALB/c mice during secondary immune response after TTd immunization with alhydrogel or glycerol as adjuvants. In addition, we followed the induced reproductive pathology as a sign of autoimmune outcome. We show undoubtedly adjuvant dependance of (1) level of induced anti-TTd IgG antibodies, (2) changes in levels of low-affinity anti-β2GPI IgG antibodies, and (3) change in fecundity and fertility during secondary immune response. These findings once more indicate the importance of chosen adjuvants used for successful immunization and eventual autoantibody outcome, this time associated with the processes involving low affinity, natural antibodies.

A dual role for the RhoGEF Ephexin5 in regulation of dendritic spine outgrowth

PubMed Central

Hamilton, AM; Lambert, JT; Parajuli, LK; Vivas, O; Park, DK; Stein, IS; Jahncke, JN; Greenberg, ME; Margolis, SS; Zito, K

2017-01-01

The outgrowth of new dendritic spines is closely linked to the formation of new synapses, and is thought to be a vital component of the experience-dependent circuit plasticity that supports learning. Here, we examined the role of the RhoGEF Ephexin5 in driving activity-dependent spine outgrowth. We found that reducing Ephexin5 levels increased spine outgrowth, and increasing Ephexin5 levels decreased spine outgrowth in a GEF-dependent manner, suggesting that Ephexin5 acts as an inhibitor of spine outgrowth. Notably, we found that increased neural activity led to a proteasome-dependent reduction in the levels of Ephexin5 in neuronal dendrites, which could facilitate the enhanced spine outgrowth observed following increased neural activity. Surprisingly, we also found that Ephexin5-GFP levels were elevated on the dendrite at sites of future new spines, prior to new spine outgrowth. Moreover, lowering neuronal Ephexin5 levels inhibited new spine outgrowth in response to both global increases in neural activity and local glutamatergic stimulation of the dendrite, suggesting that Ephexin5 is necessary for activity-dependent spine outgrowth. Our data support a model in which Ephexin5 serves a dual role in spinogenesis, acting both as a brake on overall spine outgrowth and as a necessary component in the site-specific formation of new spines. PMID:28185854

A dual role for the RhoGEF Ephexin5 in regulation of dendritic spine outgrowth.

PubMed

Hamilton, A M; Lambert, J T; Parajuli, L K; Vivas, O; Park, D K; Stein, I S; Jahncke, J N; Greenberg, M E; Margolis, S S; Zito, K

2017-04-01

The outgrowth of new dendritic spines is closely linked to the formation of new synapses, and is thought to be a vital component of the experience-dependent circuit plasticity that supports learning. Here, we examined the role of the RhoGEF Ephexin5 in driving activity-dependent spine outgrowth. We found that reducing Ephexin5 levels increased spine outgrowth, and increasing Ephexin5 levels decreased spine outgrowth in a GEF-dependent manner, suggesting that Ephexin5 acts as an inhibitor of spine outgrowth. Notably, we found that increased neural activity led to a proteasome-dependent reduction in the levels of Ephexin5 in neuronal dendrites, which could facilitate the enhanced spine outgrowth observed following increased neural activity. Surprisingly, we also found that Ephexin5-GFP levels were elevated on the dendrite at sites of future new spines, prior to new spine outgrowth. Moreover, lowering neuronal Ephexin5 levels inhibited new spine outgrowth in response to both global increases in neural activity and local glutamatergic stimulation of the dendrite, suggesting that Ephexin5 is necessary for activity-dependent spine outgrowth. Our data support a model in which Ephexin5 serves a dual role in spinogenesis, acting both as a brake on overall spine outgrowth and as a necessary component in the site-specific formation of new spines. Copyright © 2017 Elsevier Inc. All rights reserved.

Oxygen Level and LFP in Task-Positive and Task-Negative Areas: Bridging BOLD fMRI and Electrophysiology

PubMed Central

Bentley, William J.; Li, Jingfeng M.; Snyder, Abraham Z.; Raichle, Marcus E.; Snyder, Lawrence H.

2016-01-01

The human default mode network (DMN) shows decreased blood oxygen level dependent (BOLD) signals in response to a wide range of attention-demanding tasks. Our understanding of the specifics regarding the neural activity underlying these “task-negative” BOLD responses remains incomplete. We paired oxygen polarography, an electrode-based oxygen measurement technique, with standard electrophysiological recording to assess the relationship of oxygen and neural activity in task-negative posterior cingulate cortex (PCC), a hub of the DMN, and visually responsive task-positive area V3 in the awake macaque. In response to engaging visual stimulation, oxygen, LFP power, and multi-unit activity in PCC showed transient activation followed by sustained suppression. In V3, oxygen, LFP power, and multi-unit activity showed an initial phasic response to the stimulus followed by sustained activation. Oxygen responses were correlated with LFP power in both areas, although the apparent hemodynamic coupling between oxygen level and electrophysiology differed across areas. Our results suggest that oxygen responses reflect changes in LFP power and multi-unit activity and that either the coupling of neural activity to blood flow and metabolism differs between PCC and V3 or computing a linear transformation from a single LFP band to oxygen level does not capture the true physiological process. PMID:25385710

Mast Cell Dependent Vascular Changes Associated with an Acute Response to Cold Immersion in Primary Contact Urticaria

PubMed Central

Meyer, Joseph; Gorbach, Alexander M.; Liu, Wei-Min; Medic, Nevenka; Young, Michael; Nelson, Celeste; Arceo, Sarah; Desai, Avanti; Metcalfe, Dean D.; Komarow, Hirsh D.

2013-01-01

Background While a number of the consequences of mast cell degranulation within tissues have been documented including tissue-specific changes such as bronchospasm and the subsequent cellular infiltrate, there is little known about the immediate effects of mast cell degranulation on the associated vasculature, critical to understanding the evolution of mast cell dependent inflammation. Objective To characterize the microcirculatory events that follow mast cell degranulation. Methodology/Principal Findings Perturbations in dermal blood flow, temperature and skin color were analyzed using laser-speckle contrast imaging, infrared and polarized-light colorimetry following cold-hand immersion (CHI) challenge in patients with cold-induced urticaria compared to the response in healthy controls. Evidence for mast cell degranulation was established by documentation of serum histamine levels and the localized release of tryptase in post-challenge urticarial biopsies. Laser-speckle contrast imaging quantified the attenuated response to cold challenge in patients on cetirizine. We found that the histamine-associated vascular response accompanying mast cell degranulation is rapid and extensive. At the tissue level, it is characterized by a uniform pattern of increased blood flow, thermal warming, vasodilation, and recruitment of collateral circulation. These vascular responses are modified by the administration of an antihistamine. Conclusions/Significance Monitoring the hemodynamic responses within tissues that are associated with mast cell degranulation provides additional insight into the evolution of the acute inflammatory response and offers a unique approach to assess the effectiveness of treatment intervention. PMID:23451084

Hunger-Dependent Enhancement of Food Cue Responses in Mouse Postrhinal Cortex and Lateral Amygdala.

PubMed

Burgess, Christian R; Ramesh, Rohan N; Sugden, Arthur U; Levandowski, Kirsten M; Minnig, Margaret A; Fenselau, Henning; Lowell, Bradford B; Andermann, Mark L

2016-09-07

The needs of the body can direct behavioral and neural processing toward motivationally relevant sensory cues. For example, human imaging studies have consistently found specific cortical areas with biased responses to food-associated visual cues in hungry subjects, but not in sated subjects. To obtain a cellular-level understanding of these hunger-dependent cortical response biases, we performed chronic two-photon calcium imaging in postrhinal association cortex (POR) and primary visual cortex (V1) of behaving mice. As in humans, neurons in mouse POR, but not V1, exhibited biases toward food-associated cues that were abolished by satiety. This emergent bias was mirrored by the innervation pattern of amygdalo-cortical feedback axons. Strikingly, these axons exhibited even stronger food cue biases and sensitivity to hunger state and trial history. These findings highlight a direct pathway by which the lateral amygdala may contribute to state-dependent cortical processing of motivationally relevant sensory cues. Published by Elsevier Inc.

Activation of cGAS-dependent antiviral responses by DNA intercalating agents

PubMed Central

Pépin, Geneviève; Nejad, Charlotte; Thomas, Belinda J.; Ferrand, Jonathan; McArthur, Kate; Bardin, Philip G.; Williams, Bryan R.G.; Gantier, Michael P.

2017-01-01

Acridine dyes, including proflavine and acriflavine, were commonly used as antiseptics before the advent of penicillins in the mid-1940s. While their mode of action on pathogens was originally attributed to their DNA intercalating activity, work in the early 1970s suggested involvement of the host immune responses, characterized by induction of interferon (IFN)-like activities through an unknown mechanism. We demonstrate here that sub-toxic concentrations of a mixture of acriflavine and proflavine instigate a cyclic-GMP-AMP (cGAMP) synthase (cGAS)-dependent type-I IFN antiviral response. This pertains to the capacity of these compounds to induce low level DNA damage and cytoplasmic DNA leakage, resulting in cGAS-dependent cGAMP-like activity. Critically, acriflavine:proflavine pre-treatment of human primary bronchial epithelial cells significantly reduced rhinovirus infection. Collectively, our findings constitute the first evidence that non-toxic DNA binding agents have the capacity to act as indirect agonists of cGAS, to exert potent antiviral effects in mammalian cells. PMID:27694309

Does Employer-Provided Health Insurance Constrain Labor Supply Adjustments to Health Shocks? New Evidence on Women Diagnosed with Breast Cancer

PubMed Central

Neumark, David; Barkowski, Scott

2013-01-01

Employment-contingent health insurance may create incentives for ill workers to remain employed at a sufficient level (usually full-time) to maintain access to health insurance coverage. We study employed married women, comparing the labor supply responses to new breast cancer diagnoses of women dependent on their own employment for health insurance with the responses of women who are less dependent on their own employment for health insurance, because of actual or potential access to health insurance through their spouse’s employer. We find evidence that women who depend on their own job for health insurance reduce their labor supply by less after a diagnosis of breast cancer. In the estimates that best control for unobservables associated with health insurance status, the hours reduction for women who continue to work is 8 to 11 percent smaller. Women’s subjective responses to questions about working more to maintain health insurance are consistent with the conclusions from observed behavior. PMID:23891911

Plug-and-Play Multicellular Circuits with Time-Dependent Dynamic Responses.

PubMed

Urrios, Arturo; Gonzalez-Flo, Eva; Canadell, David; de Nadal, Eulàlia; Macia, Javier; Posas, Francesc

2018-04-20

Synthetic biology studies aim to develop cellular devices for biomedical applications. These devices, based on living instead of electronic or electromechanic technology, might provide alternative treatments for a wide range of diseases. However, the feasibility of these devices depends, in many cases, on complex genetic circuits that must fulfill physiological requirements. In this work, we explored the potential of multicellular architectures to act as an alternative to complex circuits for implementation of new devices. As a proof of concept, we developed specific circuits for insulin or glucagon production in response to different glucose levels. Here, we show that fundamental features, such as circuit's affinity or sensitivity, are dependent on the specific configuration of the multicellular consortia, providing a method for tuning these properties without genetic engineering. As an example, we have designed and built circuits with an incoherent feed-forward loop architecture (FFL) that can be easily adjusted to generate single pulse responses. Our results might serve as a blueprint for future development of cellular devices for glycemia regulation in diabetic patients.

Judgment of line orientation depends on gender, education, and type of error.

PubMed

Caparelli-Dáquer, Egas M; Oliveira-Souza, Ricardo; Moreira Filho, Pedro F

2009-02-01

Visuospatial tasks are particularly proficient at eliciting gender differences during neuropsychological performance. Here we tested the hypothesis that gender and education are related to different types of visuospatial errors on a task of line orientation that allowed the independent scoring of correct responses ("hits", or H) and one type of incorrect responses ("commission errors", or CE). We studied 343 volunteers of roughly comparable ages and with different levels of education. Education and gender were significantly associated with H scores, which were higher in men and in the groups with higher education. In contrast, the differences between men and women on CE depended on education. We concluded that (I) the ability to find the correct responses differs from the ability to avoid the wrong responses amidst an array of possible alternatives, and that (II) education interacts with gender to promote a stable performance on CE earlier in men than in women.

Relationship between median nerve somatosensory evoked potentials and spinal cord injury levels in patients with quadriplegia.

PubMed

de Arruda Serra Gaspar, M I F; Cliquet, A; Fernandes Lima, V M; de Abreu, D C C

2009-05-01

Cross-sectional study. To observe if there is a relationship between the level of injury by the American Spinal Cord Injury Association (ASIA) and cortical somatosensory evoked potential (SSEP) recordings of the median nerve in patients with quadriplegia. Rehabilitation Outpatient Clinic at the university hospital in Brazil. Fourteen individuals with quadriplegia and 8 healthy individuals were evaluated. Electrophysiological assessment of the median nerve was performed by evoked potential equipment. The injury level was obtained by ASIA. N(9), N(13) and N(20) were analyzed based on the presence or absence of responses. The parameters used for analyzing these responses were the latency and the amplitude. Data were analyzed using mixed-effect models. N(9) responses were found in all patients with quadriplegia with a similar latency and amplitude observed in healthy individuals; N(13) responses were not found in any patients with quadriplegia. N(20) responses were not found in C5 patients with quadriplegia but it was present in C6 and C7 patients. Their latencies were similar to healthy individuals (P>0.05) but the amplitudes were decreased (P<0.05). This study suggests that the SSEP responses depend on the injury level, considering that the individuals with C6 and C7 injury levels, both complete and incomplete, presented SSEP recordings in the cortical area. It also showed a relationship between the level of spinal cord injury assessed by ASIA and the median nerve SSEP responses, through the latency and amplitude recordings.

Inhibiting Mitochondrial DNA Ligase IIIα Activates Caspase 1-Dependent Apoptosis in Cancer Cells.

PubMed

Sallmyr, Annahita; Matsumoto, Yoshihiro; Roginskaya, Vera; Van Houten, Bennett; Tomkinson, Alan E

2016-09-15

Elevated levels of DNA ligase IIIα (LigIIIα) have been identified as a biomarker of an alteration in DNA repair in cancer cells that confers hypersensitivity to a LigIIIα inhibitor, L67, in combination with a poly (ADP-ribose) polymerase inhibitor. Because LigIIIα functions in the nucleus and mitochondria, we examined the effect of L67 on these organelles. Here, we show that, although the DNA ligase inhibitor selectively targets mitochondria, cancer and nonmalignant cells respond differently to disruption of mitochondrial DNA metabolism. Inhibition of mitochondrial LigIIIα in cancer cells resulted in abnormal mitochondrial morphology, reduced levels of mitochondrial DNA, and increased levels of mitochondrially generated reactive oxygen species that caused nuclear DNA damage. In contrast, these effects did not occur in nonmalignant cells. Furthermore, inhibition of mitochondrial LigIIIα activated a caspase 1-dependent apoptotic pathway, which is known to be part of inflammatory responses induced by pathogenic microorganisms in cancer, but not nonmalignant cells. These results demonstrate that the disruption of mitochondrial DNA metabolism elicits different responses in nonmalignant and cancer cells and suggests that the abnormal response in cancer cells may be exploited in the development of novel therapeutic strategies that selectively target cancer cells. Cancer Res; 76(18); 5431-41. ©2016 AACR. ©2016 American Association for Cancer Research.

Epiphytic lichenosynusia under conditions of chemical pollution: Dose-effect dependencies

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

Mikhailova, I.N.; Vorobeichik, E.L.

1995-11-01

The dose-effect dependencies, which characterize response of the epiphytic lichenosynusia of southern taiga in the Middle Urals to pollution by discharges of a copper-smelting plant, are substantially non-linear and, in most cases, have an S-shaped form. A transition from background to impact state is very sharp and begins when the background level of pollution is exceeded by 1.5 - 2.3 times.

Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals.

PubMed

Kim, Seong-Gi; Ogawa, Seiji

2012-07-01

After its discovery in 1990, blood oxygenation level-dependent (BOLD) contrast in functional magnetic resonance imaging (fMRI) has been widely used to map brain activation in humans and animals. Since fMRI relies on signal changes induced by neural activity, its signal source can be complex and is also dependent on imaging parameters and techniques. In this review, we identify and describe the origins of BOLD fMRI signals, including the topics of (1) effects of spin density, volume fraction, inflow, perfusion, and susceptibility as potential contributors to BOLD fMRI, (2) intravascular and extravascular contributions to conventional gradient-echo and spin-echo BOLD fMRI, (3) spatial specificity of hemodynamic-based fMRI related to vascular architecture and intrinsic hemodynamic responses, (4) BOLD signal contributions from functional changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of O(2) utilization (CMRO(2)), (5) dynamic responses of BOLD, CBF, CMRO(2), and arterial and venous CBV, (6) potential sources of initial BOLD dips, poststimulus BOLD undershoots, and prolonged negative BOLD fMRI signals, (7) dependence of stimulus-evoked BOLD signals on baseline physiology, and (8) basis of resting-state BOLD fluctuations. These discussions are highly relevant to interpreting BOLD fMRI signals as physiological means.

Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals

PubMed Central

Kim, Seong-Gi; Ogawa, Seiji

2012-01-01

After its discovery in 1990, blood oxygenation level-dependent (BOLD) contrast in functional magnetic resonance imaging (fMRI) has been widely used to map brain activation in humans and animals. Since fMRI relies on signal changes induced by neural activity, its signal source can be complex and is also dependent on imaging parameters and techniques. In this review, we identify and describe the origins of BOLD fMRI signals, including the topics of (1) effects of spin density, volume fraction, inflow, perfusion, and susceptibility as potential contributors to BOLD fMRI, (2) intravascular and extravascular contributions to conventional gradient-echo and spin-echo BOLD fMRI, (3) spatial specificity of hemodynamic-based fMRI related to vascular architecture and intrinsic hemodynamic responses, (4) BOLD signal contributions from functional changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of O2 utilization (CMRO2), (5) dynamic responses of BOLD, CBF, CMRO2, and arterial and venous CBV, (6) potential sources of initial BOLD dips, poststimulus BOLD undershoots, and prolonged negative BOLD fMRI signals, (7) dependence of stimulus-evoked BOLD signals on baseline physiology, and (8) basis of resting-state BOLD fluctuations. These discussions are highly relevant to interpreting BOLD fMRI signals as physiological means. PMID:22395207

PDK1-dependent activation of atypical PKC leads to degradation of the p21 tumour modifier protein

PubMed Central

Scott, Mary T.; Ingram, Angela; Ball, Kathryn L.

2002-01-01

p21WAF1/CIP1 contributes to positive and negative growth control on multiple levels. We previously mapped phosphorylation sites within the C-terminal domain of p21 that regulate proliferating cell nucear antigen binding. In the current study, a kinase has been fractionated from mammalian cells that stoichiometrically phosphorylates p21 at the Ser146 site, and the enzyme has been identified as an insulin-responsive atypical protein kinase C (aPKC). Expression of PKCζ or activation of the endogenous kinase by 3-phosphoinositide dependent protein kinase-1 (PDK1) decreased the half-life of p21. Conversely, dnPKCζ or dnPDK1 increased p21 protein half-life, and a PDK1-dependent increase in the rate of p21 degradation was mediated by aPKC. Insulin stimulation gave a biphasic response with a rapid transient decrease in p21 protein levels during the initial signalling phase that was dependent on phosphatidylinositol 3- kinase, PKC and proteasome activity. Thus, aPKC provides a physiological signal for the degradation of p21. The rapid degradation of p21 protein during the signalling phase of insulin stimulation identifies a novel link between energy metabolism and a key modulator of cell cycle progression. PMID:12485998

Coherence-enhanced phase-dependent dissipation in long SNS Josephson junctions: Revealing Andreev bound state dynamics

NASA Astrophysics Data System (ADS)

Dassonneville, B.; Murani, A.; Ferrier, M.; Guéron, S.; Bouchiat, H.

2018-05-01

One of the best known causes of dissipation in ac-driven quantum systems stems from photon absorption causing transitions between levels. Dissipation can also be caused by the retarded response to the time-dependent excitation, and in general gives insight into the system's relaxation times and mechanisms. Here we address the dissipation in a mesoscopic normal wire with superconducting contacts, that sustains a dissipationless supercurrent at zero frequency and that may therefore naively be expected to remain dissipationless at a frequency lower than the superconducting gap. We probe the high-frequency linear response of such a normal metal/superconductor (NS) ring to a time-dependent flux by coupling it to a highly sensitive multimode microwave resonator. Far from being the simple, dissipationless derivative of the supercurrent-versus-phase relation, the ring's ac susceptibility also displays a dissipative component whose phase dependence is a signature of the dynamical processes occurring within the Andreev spectrum. We show how dissipation is driven by the competition between two mechanisms. The first is the relaxation of the Andreev level distribution function, while the second corresponds to microwave-induced transitions within the spectrum. Depending on the relative strength of those contributions, dissipation can be maximal at π , a phase at which the proximity-induced minigap closes, or can be maximal near π /2 , a phase at which the dc supercurrent is maximal. We also find that the dissipative response paradoxically increases at low temperature and can even exceed the normal-state conductance. The results are successfully confronted with theoretical predictions of the Kubo linear response and time-dependent Usadel equations, derived from the Bogoliubov-de Gennes Hamiltonian describing the SNS junction. These experiments thus demonstrate the power of the ac susceptibility measurement of individual hybrid mesoscopic systems in probing in a controlled way the quantum dynamics of Andreev bound states. By spanning different physical regimes, our experiments provide unique access to inelastic scattering and spectroscopy of an isolated quantum coherent system, and reveal the associated relaxation times. This technique should be a tool of choice to investigate topological superconductivity and detect the topological protection of edge states.

Forecasts of county-level land uses under three future scenarios: a technical document supporting the Forest Service 2010 RPA Assessment

Treesearch

David N. Wear

2011-01-01

Accurately forecasting future forest conditions and the implications for ecosystem services depends on understanding land use dynamics. In support of the 2010 Renewable Resources Planning Act (RPA) Assessment, we forecast changes in land uses for the coterminous United States in response to three scenarios. Our land use models forecast urbanization in response to the...

Biomass-C specific temperature responses of microbial C transformations reveal consistency regardless of microbial community structure across diverse timescales of inquiry

NASA Astrophysics Data System (ADS)

Min, K.; Buckeridge, K. M.; Ziegler, S. E.; Edwards, K. A.; Bagchi, S.; Billings, S. A.

2016-12-01

The responses of heterotrophic microbial process rates to temperature in soils are often investigated in the short-term (hours to months), making it difficult to predict longer-term temperature responses. Here, we integrate the temperature sensitivity obtained from the Arrhenius model with the concepts of microbial resistance, resilience, and susceptibility to assess temporal dynamics of microbial temperature responses. We collected soils along a boreal forest climate gradient (long-term effect), and quantified exo-enzyme activities and CO2 respiration at 5, 15, and 25°C for 84 days (relatively short-term effect). Microbial process rates were examined at two levels (per g microbial biomass-C; and per g dry soil) along with community structure, to characterize driving mechanisms for temporal patterns (e.g., size of biomass, physiological plasticity, community composition). Although temperature sensitivity of exo-enzyme activities on a per g dry soil basis showed both resistance and resilience depending on the types of exo-enzyme, biomass -C-specific responses always exhibited resistance regardless of distinct community composition. Temperature sensitivity of CO2 respiration was constant across time and different communities at both units. This study advances our knowledge in two ways. First, resistant temperature sensitivity of exo-enzymes and respiration at biomass-C specific level across distinct communities and diverse timescales indicates a common relationship between microbial physiology and temperature at a fundamental level, a useful feature allowing microbial process models to be reasonably simplified. Second, different temporal responses of exo-enzymes depending on the unit selected provide a cautionary tale for those projecting future microbial behaviors, because interpretation of ecosystem process rates may vary with the unit of observation.

Stress response in rat brain after different durations of noise exposure.

PubMed

Samson, James; Sheeladevi, Rathinasamy; Ravindran, Rajan; Senthilvelan, Manohar

2007-01-01

The alteration in the levels of plasma corticosterone, brain norepinephrine (NE), and expression of brain heat shock proteins (Hsp70) after different durations of noise exposure (acute, 1 day; sub-acute, 15 days; chronic, 30 days) has been studied to analyze their role in combating time-dependent stress effects of noise. Broadband white noise (100dB) exposure to male Wistar albino rats significantly increased the levels of plasma corticosterone and NE in all three durations of noise exposure. The sustained increase observed in their levels in the chronic group suggests that animals are not getting adapted to noise even after 30 days of exposure. The important role of Hsp70 in combating noise induced stress is evident from the significant increase in its expression after chronic exposure, while there was a reciprocal decrease in the NE and corticosterone when compared with their levels after acute and sub-acute noise exposure. This clearly indicates that the time-dependent stress response to noise exposure is a complex mechanism involving highly interconnected systems such as hypothalamo-pituitary-adrenal (HPA) axis, heat shock proteins and may have serious implications in vital organs, particularly in the brain when there is a prolonged noise exposure.

Zinc chelation decreases IFN-β-induced STAT1 upregulation and iNOS expression in RAW 264.7 macrophages.

PubMed

Reiber, Cathleen; Brieger, Anne; Engelhardt, Gabriela; Hebel, Silke; Rink, Lothar; Haase, Hajo

2017-12-01

One consequence of lipopolysaccharide (LPS)-induced stimulation of macrophages is the release of Interferon (IFN)-β, and subsequently the activation of the JAK-STAT1 pathway, resulting in the expression of inducible nitric oxide synthase (iNOS). Free intracellular zinc ions (Zn 2+ ) have a profound impact as a second messenger in LPS-dependent gene expression. Previous work had indicated a Zn 2+ -dependent upregulation of STAT1 mRNA in response to LPS and IFN-β, potentially affecting STAT1-dependent downstream signaling upon pre-incubation with these agents. The aim of the present study was to investigate the long-term influence of Zn 2+ chelation on cellular STAT1 levels and their effect on protein levels and activity of iNOS. The LPS- and IFN-β-mediated increase of STAT1 mRNA and protein levels was abrogated by chelation of Zn 2+ with the membrane permeable chelator N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) in RAW 264.7 macrophages. After 48h pre-incubation together with IFN-β, TPEN also led to reduced nitric monoxide formation in response to a second stimulation with LPS. Nonetheless, the latter was observed regardless of any pre-incubation with IFN-β, suggesting that the effect of treatment with TPEN negatively affects iNOS induction independently from cellular STAT1 levels. In conclusion, long term Zn 2+ chelation does affect STAT1 protein expression, but interferes with NO production by a different, yet unknown pathway not involving STAT1. However, as there are many additional STAT1-dependent genes, there might still be effects on targets other than iNOS. Copyright © 2017 Elsevier GmbH. All rights reserved.

The tricks of the trait: neural implementation of personality varies with genotype-dependent serotonin levels.

PubMed

Hahn, Tim; Heinzel, Sebastian; Notebaert, Karolien; Dresler, Thomas; Reif, Andreas; Lesch, Klaus-Peter; Jakob, Peter M; Windmann, Sabine; Fallgatter, Andreas J

2013-11-01

Gray's Reinforcement Sensitivity Theory (RST) has developed into one of the most prominent personality theories of the last decades. The RST postulates a Behavioral Inhibition System (BIS) modulating the reaction to stimuli indicating aversive events. A number of psychiatric disorders including depression, anxiety disorders, and psychosomatic illnesses have been associated with extreme BIS responsiveness. In recent years, neuroimaging studies have implicated the amygdala-septo-hippocampal circuit as an important neural substrate of the BIS. However, the neurogenetic basis of the regulation of this behaviorally and clinically essential system remains unclear. Investigating the effects of two functional genetic polymorphisms (tryptophan hydroxylase-2, G-703T, and serotonin transporter, serotonin transporter gene-linked polymorphic region) in 89 human participants, we find significantly different patterns of associations between BIS scores and amygdala-hippocampus connectivity during loss anticipation for genotype groups regarding both polymorphisms. Specifically, the correlation between amygdala-hippocampus connectivity and Gray's trait anxiety scores is positive in individuals homozygous for the TPH2 G-allele, while carriers of at least one T-allele show a negative association. Likewise, individuals homozygous for the 5-HTTLPR L(A) variant display a positive association while carriers of the S/L(G) allele show a trend towards a negative association. Thus, we show converging evidence of different neural implementation of the BIS depending on genotype-dependent levels of serotonin. We provide evidence suggesting that genotype-dependent serotonin levels and thus putative changes in the efficiency of serotonergic neurotransmission might not only alter brain activation levels directly, but also more fundamentally impact the neural implementation of personality traits. We outline the direct clinical implications arising from this finding and discuss the complex interplay of neural responses, genes and personality traits in this context. Copyright © 2013 Elsevier Inc. All rights reserved.

Light-dependent activation of phosphoenolpyruvate carboxylase by reversible phosphorylation in cluster roots of white lupin plants: diurnal control in response to photosynthate supply

PubMed Central

Feil, Regina; Lunn, John E.; Plaxton, William C.

2016-01-01

Background and Aims Phosphoenolpyruvate carboxylase (PEPC) is a tightly regulated enzyme that controls carbohydrate partitioning to organic acid anions (malate, citrate) excreted in copious amounts by cluster roots of inorganic phosphate (Pi)-deprived white lupin plants. Excreted malate and citrate solubilize otherwise inaccessible sources of mineralized soil Pi for plant uptake. The aim of this study was to test the hypotheses that (1) PEPC is post-translationally activated by reversible phosphorylation in cluster roots of illuminated white lupin plants, and (2) light-dependent phosphorylation of cluster root PEPC is associated with elevated intracellular levels of sucrose and its signalling metabolite, trehalose-6-phosphate. Methods White lupin plants were cultivated hydroponically at low Pi levels (≤1 µm) and subjected to various light/dark pretreatments. Cluster root PEPC activity and in vivo phosphorylation status were analysed to assess the enzyme’s diurnal, post-translational control in response to light and dark. Levels of various metabolites, including sucrose and trehalose-6-phosphate, were also quantified in cluster root extracts using enzymatic and spectrometric methods. Key Results During the daytime the cluster root PEPC was activated by phosphorylation at its conserved N-terminal seryl residue. Darkness triggered a progressive reduction in PEPC phosphorylation to undetectable levels, and this was correlated with 75–80 % decreases in concentrations of sucrose and trehalose-6- phosphate. Conclusions Reversible, light-dependent regulatory PEPC phosphorylation occurs in cluster roots of Pi-deprived white lupin plants. This likely facilitates the well-documented light- and sucrose-dependent exudation of Pi-solubilizing organic acid anions by the cluster roots. PEPC’s in vivo phosphorylation status appears to be modulated by sucrose translocated from CO2-fixing leaves into the non-photosynthetic cluster roots. PMID:27063365

Radiation response and electrical properties of polymer energy storage capacitors: PVF2, Polysulfone, and Mylar

NASA Technical Reports Server (NTRS)

Edwards, L. R.

1981-01-01

Efforts were made to develop a polymer film capacitor that is tolerant to radiation. The capacitors are to be utilized in a high voltage pulse discharge application. Radiation response data at high dose/dose rate levels are presented for polyvinylidene fluoride (PVF2), polysulfone, and Mylar. The results show that PVF2 is the most radiation tolerant while Mylar is the least tolerant. The data also show that the radiation response is quite dependent on operating electric stress.

The effect of decentralized behavioral decision making on system-level risk.

PubMed

Kaivanto, Kim

2014-12-01

Certain classes of system-level risk depend partly on decentralized lay decision making. For instance, an organization's network security risk depends partly on its employees' responses to phishing attacks. On a larger scale, the risk within a financial system depends partly on households' responses to mortgage sales pitches. Behavioral economics shows that lay decisionmakers typically depart in systematic ways from the normative rationality of expected utility (EU), and instead display heuristics and biases as captured in the more descriptively accurate prospect theory (PT). In turn, psychological studies show that successful deception ploys eschew direct logical argumentation and instead employ peripheral-route persuasion, manipulation of visceral emotions, urgency, and familiar contextual cues. The detection of phishing emails and inappropriate mortgage contracts may be framed as a binary classification task. Signal detection theory (SDT) offers the standard normative solution, formulated as an optimal cutoff threshold, for distinguishing between good/bad emails or mortgages. In this article, we extend SDT behaviorally by rederiving the optimal cutoff threshold under PT. Furthermore, we incorporate the psychology of deception into determination of SDT's discriminability parameter. With the neo-additive probability weighting function, the optimal cutoff threshold under PT is rendered unique under well-behaved sampling distributions, tractable in computation, and transparent in interpretation. The PT-based cutoff threshold is (i) independent of loss aversion and (ii) more conservative than the classical SDT cutoff threshold. Independently of any possible misalignment between individual-level and system-level misclassification costs, decentralized behavioral decisionmakers are biased toward underdetection, and system-level risk is consequently greater than in analyses predicated upon normative rationality. © 2014 Society for Risk Analysis.

Dose-dependent effects of higher methionine levels on the transcriptome and metabolome of transgenic Arabidopsis seeds.

PubMed

Cohen, Hagai; Amir, Rachel

2017-05-01

Higher methionine levels in transgenic Arabidopsis seeds trigger the accumulation of stress-related transcripts and primary metabolites. These responses depend on the levels of methionine within seeds. Methionine, a sulfur-containing amino acid, is a key metabolite in plant cells. To reveal the regulatory role of the Arabidopsis thaliana CYSTATHIONINE γ-SYNTHASE (AtCGS), methionine main regulatory enzyme, in the synthesis of methionine in seeds, we generated transgenic RNAi seeds with targeted repression of AtCGS during late developmental stages of seeds. Unexpectedly, these seeds accumulated 2.5-fold more methionine than wild-type seeds. To study the nature of these seeds, transcriptomic and primary metabolite profiling were employed using Affymetrix ATH1 microarray and gas chromatography-mass spectrometry analyses, respectively. The results were compared to transgenic Arabidopsis seeds expressing a feedback-insensitive form of AtCGS (named SSE-AtD-CGS) that were previously showed to accumulate up to sixfold more soluble methionine than wild-type seeds. Statistical assessments showed that the nature of transcriptomic and metabolic changes that occurred in RNAi::AtCGS seeds were relatively similar, but to lesser extents, to those previously reported for SSE-AtD-CGS seeds, and linked to the induction of global transcriptomic and metabolic responses associated with stronger desiccation stress. As transgenic seeds obtained by both manipulations exhibited higher, but different methionine levels, the data strongly suggest that these changes depend on the absolute amounts of methionine within seeds and much less to the expression level of AtCGS.

Preservation of nitric oxide-induced relaxation of porcine coronary artery: roles of the dimers of soluble guanylyl cyclase, phosphodiesterase type 5, and cGMP-dependent protein kinase.

PubMed

Liu, Juan; Chen, Zhengju; Ye, Liping; Liu, Huixia; Dou, Dou; Liu, Limei; Yu, Xiaoxing; Gao, Yuansheng

2014-10-01

Soluble guanylyl cyclase (sGC), phosphodiesterase type 5 (PDE5), and guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase (PKG) are all dimeric. The present study was to determine the role of their dimeric status in nitric oxide-induced vasodilatation. In isolated porcine coronary arteries, after 20 h incubation with serum-free medium, serum-containing medium, or phosphate-buffered saline solution, the protein levels of the dimers of sGC, PDE5, and PKG were diminished while the monomer levels remained unchanged, associated with reduced cGMP elevation in response to DETA NONOate and decreased PDE5 activity; the activity of PKG was not significantly altered. DETA NONOate caused a greater relaxation in arteries incubated for 20 vs. 2 h. The relaxant response was largely abolished by 1H-[1, 2, 4]oxadiazolo[4,3-a]quinoxalin-1-one, an sGC inhibitor. Zaprinast, a PDE5 inhibitor, had no effect on relaxation caused by DETA NONOate of arteries incubated for 20 h but augmented the response incubated for 2 h. A greater relaxation to 8-bromo-guanosine 3'5'-cyclic monophosphate occurred in arteries incubated for 20 than for 2 h. The protein level of the dimers but not monomers of PDE5 was reduced by dithiothreitol and unaffected by hydrogen peroxide, accompanied with decreased PDE5 activity and reduced response to DETA NONOate. These results demonstrate that the dimeric but not monomeric status of sGC and PDE5 of coronary arteries are closely related to their activities. The preserved vasodilator response after 20 h incubation may result in part from a synchronous reduction of the dimer levels of sGC and PDE5 as well as an augmented response to cGMP.

Bacterial DNA-induced NK cell IFN-gamma production is dependent on macrophage secretion of IL-12.

PubMed

Chace, J H; Hooker, N A; Mildenstein, K L; Krieg, A M; Cowdery, J S

1997-08-01

Bacterial DNA (bDNA) activates B cells and macrophages and can augment inflammatory responses by inducing release of proinflammatory cytokines. We found that bDNA stimulation of mouse spleen cells induced NK cell IFN-gamma production that was dependent upon the presence of unmethylated CpG motifs, and oligonucleotides with internal CpG motifs could also induce splenocytes to secrete IFN-gamma. The bDNA-induced IFN-gamma response was strictly macrophages dependent. While splenocytes from SCID mice secreted IFN-gamma in response to bDNA, depletion of macrophages eliminated this response. Additionally, purified NK cells did not respond to bDNA; however, addition of macrophages restored the NK cell IFN-gamma response. Coculture of NK cells with preactivated macrophages further increased bDNA-induced NK cell IFN-gamma production. Anti-IL-12 or IL-10 inhibited bDNA-induced IFN-gamma response. Treatment of purified macrophages with bDNA resulted in IL-12 secretion accompanied by an increase in IL-12 p40 mRNA level. Although isolated NK cells did not make IFN-gamma in response to bDNA, NK cells costimulated with IL-12 gained the ability to respond to bDNA. These experiments show that bDNA induces macrophage IL-12 production which, in turn, stimulates NK cell IFN-gamma production. Macrophage-derived IL-12 renders NK cells responsive to bDNA permitting an even greater IFN-gamma response to bDNA.

Cold acclimation increases levels of some heat shock protein and sirtuin isoforms in threespine stickleback.

PubMed

Teigen, Laura E; Orczewska, Julieanna I; McLaughlin, Jessica; O'Brien, Kristin M

2015-10-01

Molecular chaperones [heat shock proteins (HSPs)] increase in response to rapid changes in temperatures, but long-term acclimation to cold temperature may also warrant elevations in HSPs. In fishes, cold acclimation increases mitochondrial density and oxidative stress in some tissues, which may increase demand for HSPs. We hypothesized that levels of HSPs, as well as sirtuins (SIRTs), NAD-dependent deacetylases that mediate changes in metabolism and responses to oxidative stress (including increases in HSPs), would increase during cold acclimation of threespine stickleback (Gasterosteus aculeatus). Transcript levels of hsp70, hsc70, hsp60 and hsp90-α, sirts1-4, as well as protein levels of HSP60, HSP90 and HSC70 were quantified in liver and pectoral adductor muscle of stickleback during cold acclimation from 20 °C to 8 °C. In liver, cold acclimation stimulated a transient increase in mRNA levels of hsp60 and hsc70. Transcript levels of sirt1 and sirt2 also increased in response to cold acclimation and remained elevated. In pectoral muscle, mRNA levels of hsp60, hsp90-α, hsc70 and sirt1 all transiently increased in response to cold acclimation, while levels of sirts2-4 remained constant or declined. Similar to transcript levels, protein levels of HSC70 increased in both liver and pectoral muscle. Levels of HSP90 also increased in liver after 4 weeks at 8 °C. HSP60 remained unchanged in both tissues, as did HSP90 in pectoral muscle. Our results indicate that while both HSPs and SIRTs increase in response to cold acclimation in stickleback, the response is tissue and isoform specific, likely reflecting differences in metabolism and oxidative stress. Copyright © 2015 Elsevier Inc. All rights reserved.

A locally initiated and executed measles outbreak response immunization campaign in the nylon health district, Douala Cameroon 2011.

PubMed

Sume, Gerald Etapelong; Fouda, André Arsène Bita; Kobela, Marie; Nguelé, Salomé; Emah, Irène; Atem, Peter

2013-03-16

The Cameroon health system is divided into central, intermediate and peripheral levels. Of the 43 health districts with a measles outbreak in Cameroon in 2011, only the Nylon Health District organized a documented outbreak response immunization. We present the methods and results of the response campaign solely shouldered by the district and intermediate level. The risk group, targets and neighborhoods to be vaccinated were identified after a detailed analysis of initial cases. The intermediate level defined strategies, provided logistics, capacity building and 41% of the operational budget while 59% was completed by the peripheral level. Microsoft Office Excel 2007 was used to estimate coverage rates and to draw an epidemic curve. The response immunization campaign was organized on the 14th epidemiological week, 10 weeks after the onset of the outbreak which ended 11 weeks thereafter. A total of 15867(108.5%) children aged 9-59 months were vaccinated in five health areas at a direct cost (vaccines excluded) of 71.34FCFA ($0.143) per vaccinated child. An additional 824 children aged 9-59 months were vaccinated around the residence of notified cases in neighborhoods which were not involved in the response campaign. The number of cases after the response campaign was lower than before. Once vaccines are available, prompt outbreak response campaigns can be organized at operational level to obtain commendable results instead of depending solely on international organizations or central levels. Decision makers at the intermediate and operational levels should redeploy available funds during emergencies to prevent the development of extreme public health conditions.

Level-dependent changes in detection of temporal gaps in noise markers by adults with normal and impaired hearing

PubMed Central

Horwitz, Amy R.; Ahlstrom, Jayne B.; Dubno, Judy R.

2011-01-01

Compression in the basilar-membrane input–output response flattens the temporal envelope of a fluctuating signal when more gain is applied to lower level than higher level temporal components. As a result, level-dependent changes in gap detection for signals with different depths of envelope fluctuation and for subjects with normal and impaired hearing may reveal effects of compression. To test these assumptions, gap detection with and without a broadband noise was measured with 1 000-Hz-wide (flatter) and 50-Hz-wide (fluctuating) noise markers as a function of marker level. As marker level increased, background level also increased, maintaining a fixed acoustic signal-to-noise ratio (SNR) to minimize sensation-level effects on gap detection. Significant level-dependent changes in gap detection were observed, consistent with effects of cochlear compression. For the flatter marker, gap detection that declines with increases in level up to mid levels and improves with further increases in level may be explained by an effective flattening of the temporal envelope at mid levels, where compression effects are expected to be strongest. A flatter effective temporal envelope corresponds to a reduced effective SNR. The effects of a reduction in compression (resulting in larger effective SNRs) may contribute to better-than-normal gap detection observed for some hearing-impaired listeners. PMID:22087921

Hedonic sensitivity to low-dose ketamine is modulated by gonadal hormones in a sex-dependent manner

PubMed Central

Saland, Samantha K.; Schoepfer, Kristin J.; Kabbaj, Mohamed

2016-01-01

We recently reported a greater sensitivity of female rats to rapid antidepressant-like effects of ketamine compared to male rats, and that ovarian-derived estradiol (E2) and progesterone (P4) are essential for this response. However, to what extent testosterone may also contribute, and whether duration of response to ketamine is modulated in a sex- and hormone-dependent manner remains unclear. To explore this, we systematically investigated the influence of testosterone, estradiol and progesterone on initiation and maintenance of hedonic response to low-dose ketamine (2.5 mg/kg) in intact and gonadectomized male and female rats. Ketamine induced a sustained increase in sucrose preference of female, but not male, rats in an E2P4-dependent manner. Whereas testosterone failed to alter male treatment response, concurrent administration of P4 alone in intact males enhanced hedonic response low-dose ketamine. Treatment responsiveness in female rats only was associated with greater hippocampal BDNF levels, but not activation of key downstream signaling effectors. We provide novel evidence supporting activational roles for ovarian-, but not testicular-, derived hormones in mediating hedonic sensitivity to low-dose ketamine in female and male rats, respectively. Organizational differences may, in part, account for the persistence of sex differences following gonadectomy and selective involvement of BDNF in treatment response. PMID:26888470

Cadmium (Cd(2+)) exposure differentially elicits both cell proliferation and cell death related responses in SK-RC-45.

PubMed

Sinha, Krishnendu; Pal, Pabitra Bikash; Sil, Parames C

2014-03-01

Cadmium (Cd(2+)) is a major nephrotoxic environmental pollutant, affecting mostly proximal convoluted tubule (PCT) cells of the mammalian kidney, while conditionally Cd(2+) could also elicit protective responses with great variety and variability in different systems. The present study was designed to evaluate the molecular mechanism of Cd(2+) toxicity on human PCT derived Renal Cell Carcinoma (RCC), SK-RC-45 and compare its responses with normal human PCT derived cell line, NKE. Exposure of SK-RC-45 cells with different concentrations of CdCl2 (e.g. 0, 10 and 20μM) in serum free medium for 24h generate considerable amount of ROS, accompanied with decreased cell viability and alternations in the cellular and nuclear morphologies, heat shock responses and GCLC mediated protective responses. Also phosphatidylserine externalization, augmentation in the level of caspase-3, PARP, BAD, Apaf1 and cleaved caspase-9 along with decreased expression of Bcl2 and release of cytochrome c confirmed that, Cd(2+) dose dependently induces solely intrinsic pathway of apoptosis in SK-RC-45, independent of JNK. Furthermore, the non-toxic concentration (10μM) of Cd(2+) induced nuclear translocation of Nrf2 and increased expression in the level of HO-1 enzyme suggesting that at the milder concentration, Cd(2+) induces protective signaling pathways. On the other hand, exposure of NKE to different concentrations of CdCl2 (e.g. 0, 10, 20, 30 and 50μM) under the same conditions elevate stronger heat shock and SOD2 mediated protective responses. In contrary to the RCC PCT, the normal PCT derived cell follows JNK dependent and extrinsic pathways of apoptosis. Cumulatively, these results suggest that Cd(2+) exposure dose dependently elicit both cell proliferative and cell death related responses in SK-RC-45 cells and is differentially regulated with respect to normal kidney epithelia derived NKE cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

Intratracheal instillation of single-wall carbon nanotubes in the rat lung induces time-dependent changes in gene expression

PubMed Central

Fujita, Katsuhide; Fukuda, Makiko; Fukui, Hiroko; Horie, Masanori; Endoh, Shigehisa; Uchida, Kunio; Shichiri, Mototada; Morimoto, Yasuo; Ogami, Akira; Iwahashi, Hitoshi

2015-01-01

Abstract The use of carbon nanotubes in the industry has grown; however, little is known about their toxicological mechanism of action. Single-wall carbon nanotube (SWCNT) suspensions were administered by single intratracheal instillation in rats. Persistence of alveolar macrophage-containing granuloma was observed around the sites of SWCNT aggregation at 90 days post-instillation in 0.2-mg- or 0.4-mg-injected doses per rat. Meanwhile, gene expression profiling revealed that a large number of genes involved in the inflammatory response were markedly upregulated until 90 days or 180 days post-instillation. Subsequently, gene expression patterns were dramatically altered at 365 days post-instillation, and the number of upregulated genes involved in the inflammatory response was reduced. These results suggested that alveolar macrophage-containing granuloma reflected a characteristic of the histopathological transition period from the acute-phase to the subchronic-phase of inflammation, as well as pulmonary acute phase response persistence up to 90 or 180 days after intratracheal instillation in this experimental setting. The expression levels of the genes Ctsk, Gcgr, Gpnmb, Lilrb4, Marco, Mreg, Mt3, Padi1, Slc26a4, Spp1, Tnfsf4 and Trem2 were persistently upregulated in a dose-dependent manner until 365 days post-instillation. In addition, the expression levels of Atp6v0d2, Lpo, Mmp7, Mmp12 and Rnase9 were significantly upregulated until 754 days post-instillation. We propose that these persistently upregulated genes in the chronic-phase response following the acute-phase response act as potential biomarkers in lung tissue after SWCNT instillation. This study provides further insight into the time-dependent changes in genomic expression associated with the pulmonary toxicity of SWCNTs. PMID:24911292

Genetic ablation or pharmacological blockade of dipeptidyl peptidase IV does not impact T cell-dependent immune responses

PubMed Central

Vora, Kalpit A; Porter, Gene; Peng, Roche; Cui, Yan; Pryor, Kellyann; Eiermann, George; Zaller, Dennis M

2009-01-01

Background Current literature suggests that dipeptidyl peptidase IV (DPP-IV; CD26) plays an essential role in T-dependent immune responses, a role that could have important clinical consequences. To rigorously define the role of DPP-IV in the immune system, we evaluated genetic and pharmacological inhibition of the enzyme on T-dependent immune responses in vivo. Results The DPP-IV null animals mounted robust primary and secondary antibody responses to the T dependent antigens, 4-hydroxy-3-nitrophenylacetyl-ovalbumin (NP-Ova) and 4-hydroxy-3-nitrophenylacetyl-chicken gamma globulin (NP-CGG), which were comparable to wild type mice. Serum levels of antigen specific IgM, IgG1, IgG2a, IgG2b and IgG3 were similar between the two groups of animals. DPP-IV null animals mounted an efficient germinal center reaction by day 10 after antigen stimulation that was comparable to wild type mice. Moreover, the antibodies produced by DPP-IV null animals after repeated antigenic challenge were affinity matured. Similar observations were made using wild type animals treated with a highly selective DPP-IV inhibitor during the entire course of the experiments. T cell recall responses to ovalbumin and MOG peptide, evaluated by measuring proliferation and IL-2 release from cells isolated from draining lymph nodes, were equivalent in DPP-IV null and wild type animals. Furthermore, mice treated with DPP-IV inhibitor had intact T-cell recall responses to MOG peptide. In addition, female DPP-IV null and wild type mice treated with DPP-IV inhibitor exhibited normal and robust in vivo cytotoxic T cell responses after challenge with cells expressing the male H-Y minor histocompatibility antigen. Conclusion These data indicate Selective inhibition of DPP-IV does not impair T dependent immune responses to antigenic challenge. PMID:19358731

The reduction in small ribosomal subunit abundance in ethanol-stressed cells of Bacillus subtilis is mediated by a SigB-dependent antisense RNA.

PubMed

Mars, Ruben A T; Mendonça, Karoline; Denham, Emma L; van Dijl, Jan Maarten

2015-10-01

One of the best-characterized general stress responses in bacteria is the σB-mediated stress response of the Gram-positive soil bacterium Bacillus subtilis. The σB regulon contains approximately 200 protein-encoding genes and 136 putative regulatory RNAs. One of these σB-dependent RNAs, named S1136-S1134, was recently mapped as being transcribed from the S1136 promoter on the opposite strand of the essential rpsD gene, which encodes the ribosomal primary-binding protein S4. Accordingly, S1136-S1134 transcription results in an rpsD-overlapping antisense RNA (asRNA). Upon exposure of B. subtilis to ethanol, the S1136 promoter was found to be induced, while rpsD transcription was downregulated. By quantitative PCR, we show that the activation of transcription from the S1136 promoter is directly responsible for the downregulation of rpsD upon ethanol exposure. We also show that this downregulation of rpsD leads to a reduced level of the small (30S) ribosomal subunit upon ethanol stress. The activation of the S1136 promoter thus represents the first example of antisense transcription-mediated regulation in the general stress response of B. subtilis and implicates the reduction of ribosomal protein abundance as a new aspect in the σB-dependent stress response. We propose that the observed reduction in the level of the small ribosomal subunit, which contains the ribosome-decoding center, may protect B. subtilis cells against misreading and spurious translation of possibly toxic aberrant peptides under conditions of ethanol stress. Copyright © 2015 Elsevier B.V. All rights reserved.

Understanding heterogeneity in social anxiety disorder: dependency and self-criticism moderate fear responses to interpersonal cues.

PubMed

Kopala-Sibley, Daniel C; Zuroff, David C; Russell, Jennifer J; Moskowitz, D S

2014-06-01

This study examined how the personality traits of self-criticism and dependency moderated the effects of situational interpersonal cues on fear during interpersonal interactions among individuals with social anxiety disorder (SAD). We hypothesized that self-criticism would moderate the fear-inducing effects of situational self-consciousness and that dependency would moderate the fear-inducing effects of situational emotional insecurity. Forty SAD patients (Mage = 29.23) and matched community controls (Mage = 28.93) completed event-contingent record forms after each significant social interaction of over 5 min for a 20-day period. There were 20 female patients and 20 male patients in each group. Event-level self-consciousness was more strongly associated with elevations in fear among socially anxious patients who reported higher levels of self-criticism, while event-level emotional security was more strongly associated with decreases in fear among SAD patients who reported higher levels of dependency. These interactions were not found in the community sample. Findings support the application of personality-vulnerability models to understanding fear during social interactions in patients with SAD. Results also have implications for psychotherapeutic treatments of SAD. © 2013 The British Psychological Society.

Response to the high-dose corticotrophin stimulation test depends on plasma adrenocotropin hormone levels in septic shock.

PubMed

Llompart-Pou, Juan Antonio; Raurich, Joan Maria; Ayestarán, Ignacio; Fernández-de-Castillo, Ana G; Pérez-Bárcena, Jon; Ibáñez, Jordi

2012-06-01

The use of the high-dose corticotrophin stimulation test (HDCST) as a guide to use low-dose steroid therapy in septic shock is controversial. The adrenocotropin hormone (ACTH) constitutes the immediate stimuli to produce cortisol. We evaluated the correlation of the response to the HDCST with plasma ACTH levels in patients with septic shock. This is a retrospective review of 102 patients with septic shock in which adrenal function was evaluated using the HDCST and plasma ACTH levels were measured. Patients with a δ cortisol of 9 μg/dL or less were considered as nonresponders or with subnormal response. The association between plasma ACTH levels and the response to the HDCST was investigated. Sixty-four patients (62.7%) had a subnormal response. Plasma ACTH levels were higher in patients with subnormal response (19.8 [11.7-31.4] vs 10.0 [7.0-21.2] pg/mL; P = .002). Patients in the highest quartile of plasma ACTH had lower δ cortisol (P = .014) and higher percentage of subnormal response (P = .005). The optimal cutoff point of plasma ACTH level with fewest false classifications was 10 pg/mL (sensitivity, 0.83 [95% confidence interval, 074-0.90] and specificity, 0.50 [95% confidence interval, 0.74-0.90]). Patients with septic shock with higher plasma ACTH values presented a subnormal response to the HDCST. The number of patients who failed to the HDCST was higher as plasma ACTH increased. Copyright © 2012 Elsevier Inc. All rights reserved.

Use of total lymphoid irradiation (TLI) in studies of the T cell dependence of autoantibody production in rheumatoid arthritis

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

Tanay, A.; Strober, S.; Logue, G.L.

1984-02-01

The effect of total lymphoid irradiation (TLI) on T cell-dependent and -independent humoral immune responses was studied in patients with intractable rheumatoid arthritis (RA). The serum levels of several autoantibodies and of antibodies to diphtheria (DT) and tetanus (TT) toxoids and to pneumococcal polysaccharide (PPS; 12 antigenic types) were studied before and after TLI. In addition, the patients were given a booster injection of DT and TT and a single injection of pneumococcal vaccine after radiotherapy. Antibody levels to DT and TT decreased about twofold after TLI and did not rise significantly after a booster injection. However, there was nomore » reduction in antibody levels to PPS after TLI, and a significant rise in titers was observed after a single vaccination. The serum levels of rheumatoid factor (RF), anti-nuclear antibody (ANA), and granulocyte associated IgG rose slightly after TLI. Thus, the autoantibodies and antibodies to polysaccharides appear to be relatively independent of helper T cell function, which is markedly reduced after TLI. On the other hand, antibodies to protein antigens such as DT and TT appear to be more closely dependent upon T helper function in man, as has been reported in rodents. The findings suggest that T cell-independent autoantibody responses alone do not maintain the joint disease activity in RA, because improvement in joint disease after TLI has been reported.« less

Low-level lasers affect uncoupling protein gene expression in skin and skeletal muscle tissues

NASA Astrophysics Data System (ADS)

Canuto, K. S.; Sergio, L. P. S.; Paoli, F.; Mencalha, A. L.; Fonseca, A. S.

2016-03-01

Wavelength, frequency, power, fluence, and emission mode determine the photophysical, photochemical, and photobiological responses of biological tissues to low-level lasers. Free radicals are involved in these responses acting as second messengers in intracellular signaling processes. Irradiated cells present defenses against these chemical species to avoid unwanted effects, such as uncoupling proteins (UCPs), which are part of protective mechanisms and minimize the effects of free radical generation in mitochondria. In this work UCP2 and UCP3 mRNA gene relative expression in the skin and skeletal muscle tissues of Wistar rats exposed to low-level red and infrared lasers was evaluated. Samples of the skin and skeletal muscle tissue of Wistar rats exposed to low-level red and infrared lasers were withdrawn for total RNA extraction, cDNA synthesis, and the evaluation of gene expression by quantitative polymerase chain reaction. UCP2 and UCP3 mRNA expression was differently altered in skin and skeletal muscle tissues exposed to lasers in a wavelength-dependent effect, with the UCP3 mRNA expression dose-dependent. Alteration on UCP gene expression could be part of the biostimulation effect and is necessary to make cells exposed to red and infrared low-level lasers more resistant or capable of adapting in damaged tissues or diseases.

Estrogen-related receptor {alpha} is essential for the expression of antioxidant protection genes and mitochondrial function

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

Rangwala, Shamina M.; Li, Xiaoyan; Lindsley, Loren

2007-05-25

Estrogen-related receptor {alpha} (ERR{alpha}) is an important mediator of mitochondrial biogenesis and function. To investigate the transcriptional network controlling these phenomena, we investigated mitochondrial gene expression in embryonic fibroblasts isolated from ERR{alpha} null mice. Peroxisome proliferator-activated receptor {gamma} coactivator-1{alpha} (PGC-1{alpha}) stimulated mitochondrial gene expression program in control cells, but not in the ERR{alpha} null cells. Interestingly, the induction of levels of mitochondrial oxidative stress protection genes in response to increased PGC-1{alpha} levels was dependent on ERR{alpha}. Furthermore, we found that the PGC-1{alpha}-mediated induction of estrogen-related receptor {gamma} and nuclear respiratory factor 2 (NRF-2), was dependent on the presence of ERR{alpha}.more » Basal levels of NRF-2 were decreased in the absence of ERR{alpha}. The absence of ERR{alpha} resulted in a decrease in citrate synthase enzyme activity in response to PGC-1{alpha} overexpression. Our results indicate an essential role for ERR{alpha} as a key regulator of oxidative metabolism.« less

S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate.

PubMed

Tyrakis, Petros A; Palazon, Asis; Macias, David; Lee, Kian L; Phan, Anthony T; Veliça, Pedro; You, Jia; Chia, Grace S; Sim, Jingwei; Doedens, Andrew; Abelanet, Alice; Evans, Colin E; Griffiths, John R; Poellinger, Lorenz; Goldrath, Ananda W; Johnson, Randall S

2016-12-08

R-2-hydroxyglutarate accumulates to millimolar levels in cancer cells with gain-of-function isocitrate dehydrogenase 1/2 mutations. These levels of R-2-hydroxyglutarate affect 2-oxoglutarate-dependent dioxygenases. Both metabolite enantiomers, R- and S-2-hydroxyglutarate, are detectible in healthy individuals, yet their physiological function remains elusive. Here we show that 2-hydroxyglutarate accumulates in mouse CD8 + T cells in response to T-cell receptor triggering, and accumulates to millimolar levels in physiological oxygen conditions through a hypoxia-inducible factor 1-alpha (HIF-1α)-dependent mechanism. S-2-hydroxyglutarate predominates over R-2-hydroxyglutarate in activated T cells, and we demonstrate alterations in markers of CD8 + T-cell differentiation in response to this metabolite. Modulation of histone and DNA demethylation, as well as HIF-1α stability, mediate these effects. S-2-hydroxyglutarate treatment greatly enhances the in vivo proliferation, persistence and anti-tumour capacity of adoptively transferred CD8 + T cells. Thus, S-2-hydroxyglutarate acts as an immunometabolite that links environmental context, through a metabolic-epigenetic axis, to immune fate and function.

The immunometabolite S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate

PubMed Central

Tyrakis, Petros A.; Palazon, Asis; Macias, David; Lee, Kian. L.; Phan, Anthony. T.; Veliça, Pedro; You, Jia; Chia, Grace S.; Sim, Jingwei; Doedens, Andrew; Abelanet, Alice; Evans, Colin E.; Griffiths, John R.; Poellinger, Lorenz; Goldrath, Ananda. W.; Johnson, Randall S.

2016-01-01

R-2-hydroxyglutarate accumulates to millimolar levels in cancers with gain-of-function isocitrate dehydrogenase 1/2 mutations. These levels of R-2-hydroxyglutarate affect 2-oxoglutarate-dependent dioxygenases. Both R- and S-2-hydroxyglutarate, the other enantiomer of this metabolite, are detectible in healthy individuals, yet their physiological function remains elusive. Here we show that CD8+ T-lymphocytes accumulate 2-hydroxyglutarate in response to T-cell receptor triggering. This increases to millimolar levels in physiological oxygen conditions, via a hypoxia inducible factor 1 alpha-dependent mechanism. S-2-hydroxyglutarate predominates over R-2-hydroxyglutarate in activated T cells, and we demonstrate alterations in markers of CD8+ T-lymphocyte differentiation in response to this metabolite. Modulation of histone and DNA demethylation as well as hypoxia inducible factor 1 alpha stability mediate these effects. S-2-hydroxyglutarate treatment greatly enhances the in vivo proliferation, persistence and anti-tumour capacity of adoptively transferred CD8+ T-lymphocytes. Thus S-2-hydroxyglutarate acts as an immunometabolite that links environmental context, via a metabolic-epigenetic axis, to immune fate and function. PMID:27798602

Dietary regulation of hypodermal polyploidization in C. elegans

PubMed Central

Tain, Luke S; Lozano, Encarnación; Sáez, Alberto G; Leroi, Armand M

2008-01-01

Background Dietary restriction (DR) results in increased longevity, reduced fecundity and reduced growth in many organisms. Though many studies have examined the effects of DR on longevity and fecundity, few have investigated the effects on growth. Results Here we use Caenorhabditis elegans to determine the mechanisms that regulate growth under DR. We show that rather than a reduction in cell number, decreased growth in wild type C. elegans under DR is correlated with lower levels of hypodermal polyploidization. We also show that mutants lacking wild type sensory ciliated neurons are small, exhibit hypo-polyploidization and more importantly, when grown under DR, reduce their levels of endoreduplication to a lesser extent than wild type, suggesting that these neurons are required for the regulation of hypodermal polyploidization in response to DR. Similarly, we also show that the cGMP-dependent protein kinase EGL-4 and the SMA/MAB signalling pathway regulate polyploidization under DR. Conclusion We show C. elegans is capable of actively responding to food levels to regulate adult ploidy. We suggest this response is dependent on the SMA/MAB signalling pathway. PMID:18366811

Dietary regulation of hypodermal polyploidization in C. elegans.

PubMed

Tain, Luke S; Lozano, Encarnación; Sáez, Alberto G; Leroi, Armand M

2008-03-12

Dietary restriction (DR) results in increased longevity, reduced fecundity and reduced growth in many organisms. Though many studies have examined the effects of DR on longevity and fecundity, few have investigated the effects on growth. Here we use Caenorhabditis elegans to determine the mechanisms that regulate growth under DR. We show that rather than a reduction in cell number, decreased growth in wild type C. elegans under DR is correlated with lower levels of hypodermal polyploidization. We also show that mutants lacking wild type sensory ciliated neurons are small, exhibit hypo-polyploidization and more importantly, when grown under DR, reduce their levels of endoreduplication to a lesser extent than wild type, suggesting that these neurons are required for the regulation of hypodermal polyploidization in response to DR. Similarly, we also show that the cGMP-dependent protein kinase EGL-4 and the SMA/MAB signalling pathway regulate polyploidization under DR. We show C. elegans is capable of actively responding to food levels to regulate adult ploidy. We suggest this response is dependent on the SMA/MAB signalling pathway.

Analysis of the effect of numbers of aircraft operations on community annoyance

NASA Technical Reports Server (NTRS)

Connor, W. K.; Patterson, H. P.

1976-01-01

The general validity of the equivalent-energy concept as applied to community annoyance to aircraft noise has been recently questioned by investigators using a peak-dBA concept. Using data previously gathered around nine U.S. airports, empirical tests of both concepts are presented. Results show that annoyance response follows neither concept, that annoyance increases steadily with energy-mean level for constant daily operations and with numbers of operations up to 100-199 per day (then decreases for higher numbers), and that the behavior of certain response descriptors is dependent upon the statistical distributions of numbers and levels.

myo-Inositol 1,4,5-trisphosphate and Ca(2+)/calmodulin-dependent factors mediate transduction of compression-induced signals in bovine articular chondrocytes.

PubMed Central

Valhmu, Wilmot B; Raia, Frank J

2002-01-01

Although the effects of mechanical loading on chondrocyte metabolic activities have been extensively characterized, the sequence of events through which extracellular mechanical signals are transduced into chondrocytes and ultimately modulate cell activities is not well understood. Here, studies were performed to map out the sequential intracellular signalling pathways through which compression-induced signals modulate aggrecan mRNA levels in bovine articular chondrocytes. Bovine articular cartilage explants were subjected to a compressive stress of 0.1 MPa for 1 h in the presence or absence of inhibitors or antagonists of the phosphoinositol and Ca(2+)/calmodulin signalling pathways in order to determine the roles of second messengers and effector molecules of these pathways in transducing the compression-induced signals. In the absence of the inhibitors, aggrecan mRNA levels were stimulated by compression 2-4-fold relative to levels in tare-loaded (see below) explants. Treatment of the explants with graded levels of the protein kinase C inhibitor chelerythrine or bisindolylmaleimide I, followed by 1 h compressive loading, did not significantly alter the load-induced elevation of aggrecan mRNA levels. In contrast, thapsigargin, which depletes the Ins(1,4,5)P3-sensitive intracellular Ca(2+) stores, completely blocked the load response without significantly altering aggrecan mRNA levels in tare-loaded explants. Similarly, antagonists of the Ca(2+)/calmodulin signalling pathway dose-dependently or completely blocked the load-response. The results obtained demonstrate that transduction of the compression-induced aggrecan mRNA-regulating signals requires Ins(1,4,5)P3- and Ca(2+)/calmodulin-dependent signalling processes in bovine articular chondrocytes. PMID:11802800

Sensing the heat stress by Mammalian cells.

PubMed

Cates, Jordan; Graham, Garrett C; Omattage, Natalie; Pavesich, Elizabeth; Setliff, Ian; Shaw, Jack; Smith, Caitlin Lee; Lipan, Ovidiu

2011-08-11

The heat-shock response network controls the adaptation and survival of the cell against environmental stress. This network is highly conserved and is connected with many other signaling pathways. A key element of the heat-shock network is the heat-shock transcription factor-1 (HSF), which is transiently activated by elevated temperatures. HSF translocates to the nucleus upon elevated temperatures, forming homotrimeric complexes. The HSF homotrimers bind to the heat shock element on the DNA and control the expression of the hsp70 gene. The Hsp70 proteins protect cells from thermal stress. Thermal stress causes the unfolding of proteins, perturbing thus the pathways under their control. By binding to these proteins, Hsp70 allows them to refold and prevents their aggregation. The modulation of the activity of the hsp70-promoter by the intensity of the input stress is thus critical for cell's survival. The promoter activity starts from a basal level and rapidly increases once the stress is applied, reaches a maximum level and attenuates slowely back to the basal level. This phenomenon is the hallmark of many experimental studies and of all computational network analysis. The molecular construct used as a measure of the response to thermal stress is a Hsp70-GFP fusion gene transfected in Chinese hamster ovary (CHO) cells. The time profile of the GFP protein depends on the transient activity, Transient(t), of the heat shock system. The function Transient(t) depends on hsp70 promoter activity, transcriptional regulation and the translation initiation effects elicited by the heat stress. The GFP time profile is recorded using flow cytometry measurements, a technique that allows a quantitative measurement of the fluorescence of a large number of cells (104). The GFP responses to one and two heat shocks were measured for 261 conditions of different temperatures and durations. We found that: (i) the response of the cell to two consecutive shocks (i.e., no recovery time in between shocks) depends on the order of the input shocks, that is the shocks do not commute; (ii) the responses may be classified as mild or severe, depending on the temperature level and the duration of the heat shock and (iii) the response is highly sensitive to small variations in temperature. We propose a mathematical model that maps temperature into the transient activity using experimental data that describes the time course of the response to input thermal stress. The model is built on thermotolerance without recovery time, sharp sensitivity to small variations in temperature and the existence of mild and severe classes of stress responses. The theoretical predictions are tested against experimental data using a series of double-shock inputs. The theoretical structure is represented by a sequence of three cascade processes that transform the input stress into the transient activity. The structure of the cascade is nonlinear-linear-nonlinear (NLN). The first nonlinear system (N) from the NLN structure represents the amplification of small changes in the environmental temperature; the linear system (L) represents the thermotolerance without recovery time, whereas the last system (N) represents the transition of the cell's response from a mild to a severe shock.

Behavioural fever is a synergic signal amplifying the innate immune response.

PubMed

Boltaña, Sebastian; Rey, Sonia; Roher, Nerea; Vargas, Reynaldo; Huerta, Mario; Huntingford, Felicity Anne; Goetz, Frederick William; Moore, Janice; Garcia-Valtanen, Pablo; Estepa, Amparo; Mackenzie, S

2013-09-07

Behavioural fever, defined as an acute change in thermal preference driven by pathogen recognition, has been reported in a variety of invertebrates and ectothermic vertebrates. It has been suggested, but so far not confirmed, that such changes in thermal regime favour the immune response and thus promote survival. Here, we show that zebrafish display behavioural fever that acts to promote extensive and highly specific temperature-dependent changes in the brain transcriptome. The observed coupling of the immune response to fever acts at the gene-environment level to promote a robust, highly specific time-dependent anti-viral response that, under viral infection, increases survival. Fish that are not offered a choice of temperatures and that therefore cannot express behavioural fever show decreased survival under viral challenge. This phenomenon provides an underlying explanation for the varied functional responses observed during systemic fever. Given the effects of behavioural fever on survival and the fact that it exists across considerable phylogenetic space, such immunity-environment interactions are likely to be under strong positive selection.

The role of accessory cells in polyclonal T cell activation. I. Both induction of interleukin 2 production and of interleukin 2 responsiveness by concanavalin A are accessory cell dependent.

PubMed

Hünig, T; Loos, M; Schimpl, A

1983-01-01

Recent studies from other laboratories have shown that concanavalin A (Con A) acts at two separate steps in polyclonal T cell activation: interleukin 2 (IL2) production, and induction of responsiveness to IL2. Using a combination of techniques for the depletion of accessory cells from lymph node T cells, we have investigated which of these steps, if not both, is responsible for the known requirement for accessory cells in the Con A response. It was found that with increasing T cell purification, first the ability is lost to produce sufficient levels of endogenous IL2, whereas induction of IL2 responsiveness can still take place. Further removal of accessory cells however yields a population of resting T cells that cannot be induced by Con A to become IL2-reactive. It was concluded that both IL2 production and induction of reactivity to IL2 are accessory cell-dependent events.

Decreased Arteriolar Tetrahydrobiopterin is Linked to Superoxide Generation from Nitric Oxide Synthase in Mice Fed High Salt

PubMed Central

Nurkiewicz, Timothy R.; Wu, Guoyao; Li, Peng; Boegehold, Matthew A.

2012-01-01

Objective Impaired endothelium-dependent arteriolar dilation in mice fed high salt is due to local oxidation of nitric oxide (NO) by superoxide anion (O2-). We explored the possibility that “uncoupled” endothelial nitric oxide synthase (eNOS) is the source of this O2-. Methods Levels of L-arginine (L-Arg), tetrahydrobiopterin (BH4) and O2- (hydroethidine oxidation) were measured in spinotrapezius muscle arterioles of mice fed normal salt (0.45%, NS) or high salt (4%, HS) diets for 4 weeks, with or without dietary L-Arg supplementation. The contribution of NO to endothelium-dependent dilation was determined from the effect of Nω-nitro-L-arginine methyl ester (L-NAME) on responses to acetylcholine (ACh). Results Arterioles in HS mice had lower [BH4] and higher O2- levels than those in NS mice. ACh further increased arteriolar O2- in HS mice only. L-Arg supplementation prevented the reduction in [BH4] in arterioles of HS mice, and O2- was not elevated in these vessels. Compared to NS mice, arteriolar ACh responses were diminished and insensitive to L-NAME in HS mice, but not in HS mice supplemented with L-Arg. Conclusions These findings suggest that eNOS uncoupling due to low [BH4] is responsible for O2- generation and reduced NO-dependent dilation in arterioles of mice fed a high salt diet. PMID:20163541

Learning-Dependent Plasticity of the Barrel Cortex Is Impaired by Restricting GABA-Ergic Transmission.

PubMed

Posluszny, Anna; Liguz-Lecznar, Monika; Turzynska, Danuta; Zakrzewska, Renata; Bielecki, Maksymilian; Kossut, Malgorzata

2015-01-01

Experience-induced plastic changes in the cerebral cortex are accompanied by alterations in excitatory and inhibitory transmission. Increased excitatory drive, necessary for plasticity, precedes the occurrence of plastic change, while decreased inhibitory signaling often facilitates plasticity. However, an increase of inhibitory interactions was noted in some instances of experience-dependent changes. We previously reported an increase in the number of inhibitory markers in the barrel cortex of mice after fear conditioning engaging vibrissae, observed concurrently with enlargement of the cortical representational area of the row of vibrissae receiving conditioned stimulus (CS). We also observed that an increase of GABA level accompanied the conditioning. Here, to find whether unaltered GABAergic signaling is necessary for learning-dependent rewiring in the murine barrel cortex, we locally decreased GABA production in the barrel cortex or reduced transmission through GABAA receptors (GABAARs) at the time of the conditioning. Injections of 3-mercaptopropionic acid (3-MPA), an inhibitor of glutamic acid decarboxylase (GAD), into the barrel cortex prevented learning-induced enlargement of the conditioned vibrissae representation. A similar effect was observed after injection of gabazine, an antagonist of GABAARs. At the behavioral level, consistent conditioned response (cessation of head movements in response to CS) was impaired. These results show that appropriate functioning of the GABAergic system is required for both manifestation of functional cortical representation plasticity and for the development of a conditioned response.

Hepcidin Response to Iron Therapy in Patients with Non-Dialysis Dependent CKD: An Analysis of the FIND-CKD Trial.

PubMed

Gaillard, Carlo A; Bock, Andreas H; Carrera, Fernando; Eckardt, Kai-Uwe; Van Wyck, David B; Bansal, Sukhvinder S; Cronin, Maureen; Meier, Yvonne; Larroque, Sylvain; Roger, Simon D; Macdougall, Iain C

2016-01-01

Hepcidin is the key regulator of iron homeostasis but data are limited regarding its temporal response to iron therapy, and response to intravenous versus oral iron. In the 56-week, open-label, multicenter, prospective, randomized FIND-CKD study, 626 anemic patients with non-dialysis dependent chronic kidney disease (ND-CKD) and iron deficiency not receiving an erythropoiesis stimulating agent were randomized (1:1:2) to intravenous ferric carboxymaltose (FCM), targeting higher (400-600μg/L) or lower (100-200μg/L) ferritin, or to oral iron. Serum hepcidin levels were measured centrally in a subset of 61 patients. Mean (SD) baseline hepcidin level was 4.0(3.5), 7.3(6.4) and 6.5(5.6) ng/mL in the high ferritin FCM (n = 17), low ferritin FCM (n = 16) and oral iron group (n = 28). The mean (SD) endpoint value (i.e. the last post-baseline value) was 26.0(9.1),15.7(7.7) and 16.3(11.0) ng/mL, respectively. The increase in hepcidin from baseline was significantly smaller with low ferritin FCM or oral iron vs high ferritin FCM at all time points up to week 52. Significant correlations were found between absolute hepcidin and ferritin values (r = 0.65, p<0.001) and between final post-baseline increases in both parameters (r = 0.70, p<0.001). The increase in hepcidin levels over the 12-month study generally mirrored the cumulative iron dose in each group. Hepcidin and transferrin saturation (TSAT) absolute values showed no correlation, although there was an association between final post-baseline increases (r = 0.42, p<0.001). Absolute values (r = 0.36, p = 0.004) and final post-baseline increases of hepcidin and hemoglobin (p = 0.30, p = 0.030) correlated weakly. Baseline hepcidin levels were not predictive of a hematopoietic response to iron therapy. In conclusion, hepcidin levels rose in response to either intravenous or oral iron therapy, but the speed and extent of the rise was greatest with intravenous iron targeting a higher ferritin level. However neither the baseline level nor the change in hepcidin was able to predict response to therapy in this cohort.

Analysis of plant hormone profiles in response to moderate dehydration stress.

PubMed

Urano, Kaoru; Maruyama, Kyonoshin; Jikumaru, Yusuke; Kamiya, Yuji; Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

2017-04-01

Plant responses to dehydration stress are mediated by highly complex molecular systems involving hormone signaling and metabolism, particularly the major stress hormone abscisic acid (ABA) and ABA-dependent gene expression. To understand the roles of plant hormones and their interactions during dehydration, we analyzed the plant hormone profiles with respect to dehydration responses in Arabidopsis thaliana wild-type (WT) plants and ABA biosynthesis mutants (nced3-2). We developed a procedure for moderate dehydration stress, and then investigated temporal changes in the profiles of ABA, jasmonic acid isoleucine (JA-Ile), salicylic acid (SA), cytokinin (trans-zeatin, tZ), auxin (indole-acetic acid, IAA), and gibberellin (GA 4 ), along with temporal changes in the expression of key genes involved in hormone biosynthesis. ABA levels increased in a bi-phasic pattern (at the early and late phases) in response to moderate dehydration stress. JA-Ile levels increased slightly in WT plants and strongly increased in nced3-2 mutant plants at 72 h after the onset of dehydration. The expression profiles of dehydration-inducible genes displayed temporal responses in an ABA-dependent manner. The early phase of ABA accumulation correlated with the expression of touch-inducible genes and was independent of factors involved in the major ABA regulatory pathway, including the ABA-responsive element-binding (AREB/ABF) transcription factor. JA-Ile, SA, and tZ were negatively regulated during the late dehydration response phase. Transcriptome analysis revealed important roles for hormone-related genes in metabolism and signaling during dehydration-induced plant responses. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Paradox effects of binge drinking on response inhibition processes depending on mental workload.

PubMed

Stock, Ann-Kathrin; Riegler, Lea; Chmielewski, Witold X; Beste, Christian

2016-06-01

Binge drinking is an increasing problem in Western societies, but we are still only beginning to unravel the effects of binge drinking on a cognitive level. While common sense suggests that all cognitive functions are compromised during high-dose ethanol intoxication, several studies suggest that the effects might instead be rather specific. Moreover, some results suggest that the degrees of automaticity and complexity of cognitive operations during response control modulate effects of binge drinking. However, this has not been tested in detail. In the current study, we therefore parametrically modulate cognitive/"mental" workload during response inhibition and examine the effects of high-dose ethanol intoxication (~1.1 ‰) in n = 18 male participants. The results suggest that detrimental effects of high-dose ethanol intoxication strongly depend on the complexity of processes involved in response inhibition. The results revealed strong effects (η (2) = .495) and are in line with findings showing that even high doses of ethanol have very specific effects on a cognitive level. Opposed to common sense, more complex cognitive operations seem to be less affected by a high-dose ethanol intoxication. Complementing this, high-dose ethanol intoxication is increasingly detrimental for action control, as stronger automated response tendencies are in charge and need to be controlled. Binge-like ethanol intoxication may take a heavier toll on cognitive control processes than on automated responses/response tendencies. Therefore, ethanol effects are more pronounced in supposedly "easier" control conditions because those facilitate the formation of automated response tendencies.

Response to novelty as a predictor of cocaine sensitization and conditioning in rats: a correlational analysis.

PubMed

Carey, Robert J; DePalma, Gail; Damianopoulos, Ernest

2003-07-01

An animal's response to novelty has been suggested to be a predictor of its response to drugs of abuse. The possible relationship between an individual's behavioral response to novelty and its subsequent behavioral response to cocaine has not been subjected to a detailed correlational analysis. To use a repeated cocaine treatment protocol to induce cocaine sensitization and conditioned cocaine locomotor stimulant effects and to assess the relationship of these effects to pre-cocaine locomotor behavior in a novel environment. In two separate experiments, rats were given a 20-min test in a novel open-field environment. Subsequently, the rats were given a series of additional tests in conjunction with either saline or cocaine (10 mg/kg) treatments to induce cocaine sensitization and conditioned effects. The repeated cocaine treatments induced cocaine behavioral sensitization and conditioned effects. Correlational analyses showed that the initial 20-min novel environment test proved to be a strong predictor of an animal's subsequent saline activity level but did not predict the rats' behavioral acute and sensitized response to cocaine. When change in activity was used as the dependent variable, initial activity level was reliably negatively correlated with activity changes on cocaine tests as well as cocaine conditioning tests. The negative correlation between initial activity in a novel environment and the change in activity induced by cocaine indicates that low responders to environmental novelty tend to have the strongest response to cocaine. These results appear consistent with the classic initial value and response rate dependent analyses of stimulant drug effects.

The Endoplasmic Reticulum-Mitochondrion Tether ERMES Orchestrates Fungal Immune Evasion, Illuminating Inflammasome Responses to Hyphal Signals

PubMed Central

Tucey, Timothy M.; Verma-Gaur, Jiyoti; Nguyen, Julie; Hewitt, Victoria L.; Lo, Tricia L.; Shingu-Vazquez, Miguel; Robertson, Avril A. B.; Hill, James R.; Pettolino, Filomena A.; Beddoe, Travis; Cooper, Matthew A.; Naderer, Thomas

2016-01-01

ABSTRACT The pathogenic yeast Candida albicans escapes macrophages by triggering NLRP3 inflammasome-dependent host cell death (pyroptosis). Pyroptosis is inflammatory and must be tightly regulated by host and microbe, but the mechanism is incompletely defined. We characterized the C. albicans endoplasmic reticulum (ER)-mitochondrion tether ERMES and show that the ERMES mmm1 mutant is severely crippled in killing macrophages despite hyphal formation and normal phagocytosis and survival. To understand dynamic inflammasome responses to Candida with high spatiotemporal resolution, we established live-cell imaging for parallel detection of inflammasome activation and pyroptosis at the single-cell level. This showed that the inflammasome response to mmm1 mutant hyphae is delayed by 10 h, after which an exacerbated activation occurs. The NLRP3 inhibitor MCC950 inhibited inflammasome activation and pyroptosis by C. albicans, including exacerbated inflammasome activation by the mmm1 mutant. At the cell biology level, inactivation of ERMES led to a rapid collapse of mitochondrial tubular morphology, slow growth and hyphal elongation at host temperature, and reduced exposed 1,3-β-glucan in hyphal populations. Our data suggest that inflammasome activation by C. albicans requires a signal threshold dependent on hyphal elongation and cell wall remodeling, which could fine-tune the response relative to the level of danger posed by C. albicans. The phenotypes of the ERMES mutant and the lack of conservation in animals suggest that ERMES is a promising antifungal drug target. Our data further indicate that NLRP3 inhibition by MCC950 could modulate C. albicans-induced inflammation. IMPORTANCE The yeast Candida albicans causes human infections that have mortality rates approaching 50%. The key to developing improved therapeutics is to understand the host-pathogen interface. A critical interaction is that with macrophages: intracellular Candida triggers the NLRP3/caspase-1 inflammasome for escape through lytic host cell death, but this also activates antifungal responses. To better understand how the inflammasome response to Candida is fine-tuned, we established live-cell imaging of inflammasome activation at single-cell resolution, coupled with analysis of the fungal ERMES complex, a mitochondrial regulator that lacks human homologs. We show that ERMES mediates Candida escape via inflammasome-dependent processes, and our data suggest that inflammasome activation is controlled by the level of hyphal growth and exposure of cell wall components as a proxy for severity of danger. Our study provides the most detailed dynamic analysis of inflammasome responses to a fungal pathogen so far and establishes promising pathogen- and host-derived therapeutic strategies. PMID:27303738

The Endoplasmic Reticulum-Mitochondrion Tether ERMES Orchestrates Fungal Immune Evasion, Illuminating Inflammasome Responses to Hyphal Signals.

PubMed

Tucey, Timothy M; Verma-Gaur, Jiyoti; Nguyen, Julie; Hewitt, Victoria L; Lo, Tricia L; Shingu-Vazquez, Miguel; Robertson, Avril A B; Hill, James R; Pettolino, Filomena A; Beddoe, Travis; Cooper, Matthew A; Naderer, Thomas; Traven, Ana

2016-01-01

The pathogenic yeast Candida albicans escapes macrophages by triggering NLRP3 inflammasome-dependent host cell death (pyroptosis). Pyroptosis is inflammatory and must be tightly regulated by host and microbe, but the mechanism is incompletely defined. We characterized the C. albicans endoplasmic reticulum (ER)-mitochondrion tether ERMES and show that the ERMES mmm1 mutant is severely crippled in killing macrophages despite hyphal formation and normal phagocytosis and survival. To understand dynamic inflammasome responses to Candida with high spatiotemporal resolution, we established live-cell imaging for parallel detection of inflammasome activation and pyroptosis at the single-cell level. This showed that the inflammasome response to mmm1 mutant hyphae is delayed by 10 h, after which an exacerbated activation occurs. The NLRP3 inhibitor MCC950 inhibited inflammasome activation and pyroptosis by C. albicans, including exacerbated inflammasome activation by the mmm1 mutant. At the cell biology level, inactivation of ERMES led to a rapid collapse of mitochondrial tubular morphology, slow growth and hyphal elongation at host temperature, and reduced exposed 1,3-β-glucan in hyphal populations. Our data suggest that inflammasome activation by C. albicans requires a signal threshold dependent on hyphal elongation and cell wall remodeling, which could fine-tune the response relative to the level of danger posed by C. albicans. The phenotypes of the ERMES mutant and the lack of conservation in animals suggest that ERMES is a promising antifungal drug target. Our data further indicate that NLRP3 inhibition by MCC950 could modulate C. albicans-induced inflammation. IMPORTANCE The yeast Candida albicans causes human infections that have mortality rates approaching 50%. The key to developing improved therapeutics is to understand the host-pathogen interface. A critical interaction is that with macrophages: intracellular Candida triggers the NLRP3/caspase-1 inflammasome for escape through lytic host cell death, but this also activates antifungal responses. To better understand how the inflammasome response to Candida is fine-tuned, we established live-cell imaging of inflammasome activation at single-cell resolution, coupled with analysis of the fungal ERMES complex, a mitochondrial regulator that lacks human homologs. We show that ERMES mediates Candida escape via inflammasome-dependent processes, and our data suggest that inflammasome activation is controlled by the level of hyphal growth and exposure of cell wall components as a proxy for severity of danger. Our study provides the most detailed dynamic analysis of inflammasome responses to a fungal pathogen so far and establishes promising pathogen- and host-derived therapeutic strategies.

Comparison of estrogenic responses in bone and uterus depending on the parity status in Lewis rats.

PubMed

Keiler, Annekathrin Martina; Bernhardt, Ricardo; Scharnweber, Dieter; Jarry, Hubertus; Vollmer, Günter; Zierau, Oliver

2013-01-01

The reproductive transition of women through peri- to postmenopause is characterized by changes in steroid hormone levels due to the cessation of the ovarian function. Beside several complaints associated with these hormonal changes, the deterioration of the trabecular bone micro-architecture and the loss of skeletal mass can cause osteoporosis. At this life stage, women often have a reproductive history of one to several pregnancies. The ovariectomized skeletally mature rat (>10 months old) is one of the most commonly used animal models for postmenopausal osteoporosis research. Despite the fact that mammals can undergo up to several reproductive cycles (primi-/pluriparous), nulliparous animals are often used and the question whether changes in the hormonal milieu subsequently affect the skeleton and influence the outcome of intervention studies is often neglected in study designs. Therefore, the aim of the present study was to compare the estrogen responsiveness of nulliparous and pluriparous rats. For this purpose, one year old virgin or retired breeder Lewis rats were either sham operated or ovariectomized, whereas half of the ovariectomized animals received subcutaneous 17β-estradiol pellets eight weeks after surgery. After another four weeks, the effects on the uterus were determined by expression analysis of estrogen-dependently regulated steroid receptor genes and well-established marker genes. Moreover, trabecular bone parameters in the tibia were analyzed by micro-computed tomography (μCT). Parity-dependency in estrogen responsiveness was observed with respect to the achieved serum E2 levels in response to similar E2 treatment. This led to differences both on the uterus wet weight and on the expression level of uterine target genes. In addition, a reversal of the ovariectomy-induced changes of the bone architecture after 17β-estradiol substitution was only observed among the nulliparous. In conclusion, the observations of this study support parity-dependent differences in the responses to estrogenic compounds in the uterus and the bone of rats. These results indicate that the parity-status has an impact on the outcome of studies aiming at the investigation of estrogenic effects of compounds potentially used in hormone replacement and thus, this should be taken into consideration for further studies and particularly for the discussion of data obtained with the preclinical ovariectomized rat animal model. Copyright © 2012 Elsevier Ltd. All rights reserved.

Phytoplankton responses to temperature increases are constrained by abiotic conditions and community composition.

PubMed

Striebel, Maren; Schabhüttl, Stefanie; Hodapp, Dorothee; Hingsamer, Peter; Hillebrand, Helmut

2016-11-01

Effects of temperature changes on phytoplankton communities seem to be highly context-specific, but few studies have analyzed whether this context specificity depends on differences in the abiotic conditions or in species composition between studies. We present an experiment that allows disentangling the contribution of abiotic and biotic differences in shaping the response to two aspects of temperature change: permanent increase of mean temperature versus pulse disturbance in form of a heat wave. We used natural communities from six different sites of a floodplain system as well as artificially mixed communities from laboratory cultures and grew both, artificial and natural communities, in water from the six different floodplain lakes (sites). All 12 contexts (2 communities × 6 sites) were first exposed to three different temperature levels (12, 18, 24 °C, respectively) and afterward to temperature pulses (4 °C increase for 7 h day(-1)). Temperature-dependent changes in biomass and community composition depended on the initial composition of phytoplankton communities. Abiotic conditions had a major effect on biomass of phytoplankton communities exposed to different temperature conditions, however, the effect of biotic and abiotic conditions together was even more pronounced. Additionally, phytoplankton community responses to pulse temperature effects depended on the warming history. By disentangling abiotic and biotic effects, our study shows that temperature-dependent effects on phytoplankton communities depend on both, biotic and abiotic constraints.

Impulsivity Moderates Subjective Responses to Alcohol in Alcohol-Dependent Individuals.

PubMed

Westman, Jonathan G; Bujarski, Spencer; Ray, Lara A

2017-03-09

Studies of social drinkers indicate that subjective response (SR) to alcohol and impulsivity are risk factors for the development of alcohol use disorder which may be related. It is unclear, however, whether there are significant relationships between SR and impulsivity among individuals with alcohol dependence. Using data from an intravenous (IV) alcohol challenge study, the present study is the first to explore the relationship between impulsivity and SR during alcohol administration among alcohol-dependent individuals. Non-treatment-seeking, alcohol-dependent individuals (N = 42) completed the Delay Discounting Task to measure impulsivity and then completed two counterbalanced, placebo-controlled IV alcohol administration sessions, which included assessments of SR at breath alcohol concentration (BrAC) levels of 0.00, 0.02, 0.04 and 0.06 g/dl. Analyses revealed that more impulsive participants experienced higher subjective stimulation and positive mood in response to rising BrACs as compared to less impulsive individuals. More impulsive participants also experienced increased sedation over time regardless of condition (i.e. alcohol vs. saline). These findings suggest that among alcohol-dependent individuals, impulsivity is positively associated with the hedonic effects of alcohol as compared to placebo. High impulsivity may characterize a subset of alcohol-dependent individuals who drink to experience the rewarding effects of alcohol. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Nebivolol dilates human penile arteries and reverses erectile dysfunction in diabetic rats through enhancement of nitric oxide signaling.

PubMed

Angulo, Javier; Wright, Harold M; Cuevas, Pedro; González-Corrochano, Rocío; Fernández, Argentina; Cuevas, Begoña; La Fuente, José M; Gupta, Sandeep; Sáenz de Tejada, Iñigo

2010-08-01

Traditional beta-blockers have sometimes been associated with erectile dysfunction (ED). Nebivolol is a cardioselective β(1)-adrenoceptor antagonist that promotes vasodilation through a nitric oxide (NO)-dependent mechanism. We evaluated the effects of nebivolol on the NO/cyclic guanosine monophosphate (cGMP) signaling pathway, on erectile function and dysfunction, and in human penile vascular tissues. Erectile response to cavernosal nerve electrical stimulation in control and diabetes-induced ED rats were evaluated, along with serum nitrite/nitrate (NOx) concentration and plasma/tissue cGMP levels. Endothelium-dependent and sildenafil-induced relaxation of isolated human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) were also determined. The effects of nebivolol on erectile function and dysfunction and on NO/cGMP-mediated responses. Treatment with nebivolol significantly potentiated erectile response in control rats, regardless of its effects on blood pressure. Nebivolol increased NOx and plasma cGMP by 3-fold and 2.75-fold, respectively, and significantly augmented the elevation of plasma cGMP produced by sildenafil. Nebivolol enhanced endothelium-dependent and sildenafil-induced relaxations of HCC tissue, and produced endothelium-dependent vasodilation of HPRA. Nebivolol, but not atenolol, significantly improved erectile response in diabetic rats (51.6%, 53.2%, and 87.1% of response at 3 Hz in nondiabetic rats, for vehicle-treated, atenolol-treated, and nebivolol-treated diabetic rats, respectively); after sildenafil administration, ED was completely reversed in nebivolol-treated diabetic rats (69.6% and 112% for diabetic rats treated with sildenafil and nebivolol plus sildenafil, respectively). Accordingly, nebivolol restored systemic NOx levels and cGMP content in penile tissue from these animals. Nebivolol in vivo activated the NO/cGMP pathway, enhanced erectile response and reversed ED in diabetic rats. Moreover, nebivolol in vitro potentiated NO/cGMP-mediated relaxation of human erectile tissues. These effects may account for the low incidence of ED in nebivolol-treated hypertensive patients. Nebivolol therefore may have utility in the treatment of ED, particularly ED associated with diabetes. © 2010 International Society for Sexual Medicine.

Differential Interaction of Synthetic Glycolipids with Biomimetic Plasma Membrane Lipids Correlates with the Plant Biological Response.

PubMed

Nasir, Mehmet Nail; Lins, Laurence; Crowet, Jean-Marc; Ongena, Marc; Dorey, Stephan; Dhondt-Cordelier, Sandrine; Clément, Christophe; Bouquillon, Sandrine; Haudrechy, Arnaud; Sarazin, Catherine; Fauconnier, Marie-Laure; Nott, Katherine; Deleu, Magali

2017-09-26

Natural and synthetic amphiphilic molecules including lipopeptides, lipopolysaccharides, and glycolipids are able to induce defense mechanisms in plants. In the present work, the perception of two synthetic C14 rhamnolipids, namely, Alk-RL and Ac-RL, differing only at the level of the lipid tail terminal group have been investigated using biological and biophysical approaches. We showed that Alk-RL induces a stronger early signaling response in tobacco cell suspensions than does Ac-RL. The interactions of both synthetic RLs with simplified biomimetic membranes were further analyzed using experimental and in silico approaches. Our results indicate that the interactions of Alk-RL and Ac-RL with lipids were different in terms of insertion and molecular responses and were dependent on the lipid composition of model membranes. A more favorable insertion of Alk-RL than Ac-RL into lipid membranes is observed. Alk-RL forms more stable molecular assemblies than Ac-RL with phospholipids and sterols. At the molecular level, the presence of sterols tends to increase the RLs' interaction with lipid bilayers, with a fluidizing effect on the alkyl chains. Taken together, our findings suggest that the perception of these synthetic RLs at the membrane level could be related to a lipid-driven process depending on the organization of the membrane and the orientation of the RLs within the membrane and is correlated with the induction of early signaling responses in tobacco cells.

Estradiol selectively enhances auditory function in avian forebrain neurons

PubMed Central

Caras, Melissa L.; O’Brien, Matthew; Brenowitz, Eliot A.; Rubel, Edwin W

2012-01-01

Sex steroids modulate vertebrate sensory processing, but the impact of circulating hormone levels on forebrain function remains unclear. We tested the hypothesis that circulating sex steroids modulate single-unit responses in the avian telencephalic auditory nucleus, field L. We mimicked breeding or non-breeding conditions by manipulating plasma 17β-estradiol levels in wild-caught female Gambel’s white-crowned sparrows (Zonotrichia leucophrys gambelii). Extracellular responses of single neurons to tones and conspecific songs presented over a range of intensities revealed that estradiol selectively enhanced auditory function in cells that exhibited monotonic rate-level functions to pure tones. In these cells, estradiol treatment increased spontaneous and maximum evoked firing rates, increased pure tone response strengths and sensitivity, and expanded the range of intensities over which conspecific song stimuli elicited significant responses. Estradiol did not significantly alter the sensitivity or dynamic ranges of cells that exhibited non-monotonic rate-level functions. Notably, there was a robust correlation between plasma estradiol concentrations in individual birds and physiological response properties in monotonic, but not non-monotonic neurons. These findings demonstrate that functionally distinct classes of anatomically overlapping forebrain neurons are differentially regulated by sex steroid hormones in a dose-dependent manner. PMID:23223283

Region specific changes in nonapeptide levels during client fish interactions with allopatric and sympatric cleaner fish

PubMed Central

Soares, Marta C.; Cardoso, Sónia C.; Mazzei, Renata; André, Gonçalo I.; Morais, Marta; Gozdowska, Magdalena; Kalamarz-Kubiak, Hanna; Kulczykowska, Ewa

2017-01-01

Social relationships are crucially dependent on individual ability to learn and remember ecologically relevant cues. However, the way animals recognize cues before engaging in any social interaction and how their response is regulated by brain neuromodulators remains unclear. We examined the putative involvement of arginine vasotocin (AVT) and isotocin (IT), acting at different brain regions, during fish decision-making in the context of cooperation, by trying to identify how fish distinguish and recognize the value of other social partners or species. We hypothesized that the behavioural responses of cleaner fish clients to different social contexts would be underlain by changes in brain AVT and IT levels. We have found that changes in AVT at the level of forebrain and optic tectum are linked with a response to allopatric cleaners (novel or unfamiliar stimuli) while those at cerebellum are associated with the willingness to be cleaned (in response to sympatric cleaners). On the other hand, higher brain IT levels that were solely found in the diencephalon, also in response to allopatric cleaners. Our results are the first to implicate these nonapeptides, AVT in particular, in the assessment of social cues which enable fish to engage in mutualistic activities. PMID:28683143

Fibroblast growth factor and cyclic AMP (cAMP) synergistically activate gene expression at a cAMP response element.

PubMed Central

Tan, Y; Low, K G; Boccia, C; Grossman, J; Comb, M J

1994-01-01

Growth factors and cyclic AMP (cAMP) are known to activate distinct intracellular signaling pathways. Fibroblast growth factor (FGF) activates ras-dependent kinase cascades, resulting in the activation of MAP kinases, whereas cAMP activates protein kinase A. In this study, we report that growth factors and cAMP act synergistically to stimulate proenkephalin gene expression. Positive synergy between growth factor- and cAMP-activated signaling pathways on gene expression has not been previously reported, and we suggest that these synergistic interactions represent a useful model for analyzing interactions between these pathways. Transfection and mutational studies indicate that both FGF-dependent gene activation and cAMP-dependent gene activation require cAMP response element 2 (CRE-2), a previously characterized cAMP-dependent regulatory element. Furthermore, multiple copies of this element are sufficient to confer FGF regulation upon a minimal promoter, indicating that FGF and cAMP signaling converge upon transcription factors acting at CRE-2. Among many different ATF/AP-1 factors tested, two factors, ATF-3 and c-Jun, stimulate proenkephalin transcription in an FGF- or Ras-dependent fashion. Finally, we show that ATF-3 and c-Jun form heterodimeric complexes in SK-N-MC cells and that the levels of both proteins are increased in response to FGF but not cAMP. Together, these results indicate that growth factor- and cAMP-dependent signaling pathways converge at CRE-2 to synergistically stimulate gene expression and that ATF-3 and c-Jun regulate proenkephalin transcription in response to both growth factor- and cAMP-dependent intracellular signaling pathways. Images PMID:7935470

SYNTHETIC COPPER-CONTAINING PARTICLES ENHANCE ALLERGIC AIRWAY RESPONSES IN MICE

EPA Science Inventory

Respiratory morbidity and mortality associated with increases in ambient levels of particulate matter (PM) may be dependent on particle elemental composition. Particle-associated metals such as copper may catalyze formation of reactive oxygen species leading to inflammation and l...

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

Audigier, S.M.P.; Wang, J.K.T.; Greengard, P.

Synaptosomes, purified from rat cerebral cortex, were prelabeled with (/sup 3/H)inositol to study phosphatidylinositol turnover in nerve terminals. Labeled synaptosomes were either depolarized with 40 mM K/sup +/ or exposed to carbamoylcholine (carbachol). K/sup +/ depolarization increased the level of inositol phosphates in a time-dependent manner. The inositol bisphosphate level also increased rapidly, but its elevated level was sustained during continued depolarization. The elevated level of inositol bisphosphate was reversed upon repolarization of the synaptosomes. The level of inositol monophosphate increased slowly to 120-130% of control. These effects of K/sup +/ depolarization depended on the presence of Ca/sup 2 +/more » in the incubation medium. Carbachol stimulated the turnover of phosphatidylinositol in a dose- and time-dependent manner. The level of inositol bisphosphate increased to 210% of control, and this maximal response was seen from 15 to 60 min. Accumulation of inositol monophosphate was larger than that of inositol bisphosphate, but its time course was slower. Atropine and pirenzepine inhibited the carbachol effect with high affinities. These data show that both Ca/sup 2 +/ influx and M/sub 1/ muscarinic receptor activation stimulate phospholipase C activity in synaptosomes, suggesting that phosphatidylinositol turnover may be involved in regulating neurotransmitter release from nerve terminals.« less

Top-level dynamics and the regulated gene response of feed-forward loop transcriptional motifs.

PubMed

Mayo, Michael; Abdelzaher, Ahmed; Perkins, Edward J; Ghosh, Preetam

2014-09-01

Feed-forward loops are hierarchical three-node transcriptional subnetworks, wherein a top-level protein regulates the activity of a target gene via two paths: a direct-regulatory path, and an indirect route, whereby the top-level proteins act implicitly through an intermediate transcription factor. Using a transcriptional network of the model bacterium Escherichia coli, we confirmed that nearly all types of feed-forward loop were significantly overrepresented in the bacterial network. We then used mathematical modeling to study their dynamics by manipulating the rise times of the top-level protein concentration, termed the induction time, through alteration of the protein destruction rates. Rise times of the regulated proteins exhibited two qualitatively different regimes, depending on whether top-level inductions were "fast" or "slow." In the fast regime, rise times were nearly independent of rapid top-level inductions, indicative of biological robustness, and occurred when RNA production rate-limits the protein yield. Alternatively, the protein rise times were dependent upon slower top-level inductions, greater than approximately one bacterial cell cycle. An equation is given for this crossover, which depends upon three parameters of the direct-regulatory path: transcriptional cooperation at the DNA-binding site, a protein-DNA dissociation constant, and the relative magnitude of the top-level protien concentration.

Unraveling the concentration-dependent metabolic response of Pseudomonas sp. HF-1 to nicotine stress by ¹H NMR-based metabolomics.

PubMed

Ye, Yangfang; Wang, Xin; Zhang, Limin; Lu, Zhenmei; Yan, Xiaojun

2012-07-01

Nicotine can cause oxidative damage to organisms; however, some bacteria, for example Pseudomonas sp. HF-1, are resistant to such oxidative stress. In the present study, we analyzed the concentration-dependent metabolic response of Pseudomonas sp. HF-1 to nicotine stress using ¹H NMR spectroscopy coupled with multivariate data analysis. We found that the dominant metabolites in Pseudomonas sp. HF-1 were eight aliphatic organic acids, six amino acids, three sugars and 11 nucleotides. After 18 h of cultivation, 1 g/L nicotine caused significant elevation of sugar (glucose, trehalose and maltose), succinate and nucleic acid metabolites (cytidine, 5'-CMP, guanine 2',3'-cyclic phosphate and adenosine 2',3'-cyclic phosphate), but decrease of glutamate, putrescine, pyrimidine, 2-propanol, diethyl ether and acetamide levels. Similar metabolomic changes were induced by 2 g/L nicotine, except that no significant change in trehalose, 5'-UMP levels and diethyl ether were found. However, 3 g/L nicotine led to a significant elevation in the two sugars (trehalose and maltose) levels and decrease in the levels of glutamate, putrescine, pyrimidine and 2-propanol. Our findings indicated that nicotine resulted in the enhanced nucleotide biosynthesis, decreased glucose catabolism, elevated succinate accumulation, severe disturbance in osmoregulation and complex antioxidant strategy. And a further increase of nicotine level was a critical threshold value that triggered the change of metabolic flow in Pseudomonas sp. HF-1. These findings revealed the comprehensive insights into the metabolic response of nicotine-degrading bacteria to nicotine-induced oxidative toxicity.

Economic weights for genetic improvement of lactation persistency and milk yield.

PubMed

Togashi, K; Lin, C Y

2009-06-01

This study aimed to establish a criterion for measuring the relative weight of lactation persistency (the ratio of yield at 280 d in milk to peak yield) in restricted selection index for the improvement of net merit comprising 3-parity total yield and total lactation persistency. The restricted selection index was compared with selection based on first-lactation total milk yield (I(1)), the first-two-lactation total yield (I(2)), and first-three-lactation total yield (I(3)). Results show that genetic response in net merit due to selection on restricted selection index could be greater than, equal to, or less than that due to the unrestricted index depending upon the relative weight of lactation persistency and the restriction level imposed. When the relative weight of total lactation persistency is equal to the criterion, the restricted selection index is equal to the selection method compared (I(1), I(2), or I(3)). The restricted selection index yielded a greater response when the relative weight of total lactation persistency was above the criterion, but a lower response when it was below the criterion. The criterion varied depending upon the restriction level (c) imposed and the selection criteria compared. A curvilinear relationship (concave curve) exists between the criterion and the restricted level. The criterion increases as the restriction level deviates in either direction from 1.5. Without prior information of the economic weight of lactation persistency, the imposition of the restriction level of 1.5 on lactation persistency would maximize change in net merit. The procedure presented allows for simultaneous modification of multi-parity lactation curves.

Kinetics of ROS generation induced by polycyclic aromatic hydrocarbons and organic extracts from ambient air particulate matter in model human lung cell lines.

PubMed

Libalova, Helena; Milcova, Alena; Cervena, Tereza; Vrbova, Kristyna; Rossnerova, Andrea; Novakova, Zuzana; Topinka, Jan; Rossner, Pavel

2018-03-01

Polycyclic aromatic hydrocarbons (PAHs) associated with particulate matter (PM) may induce oxidative damage via reactive oxygen species (ROS) generation. However, the kinetics of ROS production and the link with antioxidant response induction has not been well studied. To elucidate the differences in oxidative potential of individual PAH compounds and extractable organic matter (EOM) from PM containing various PAH mixtures, we studied ROS formation and antioxidant response [total antioxidant capacity (TAC) and expression of HMOX1 and TXNRD1] in human alveolar basal epithelial cells (A549 cells) and human embryonic lung fibroblasts (HEL12469 cells). We treated the cells with three concentrations of model PAHs (benzo[a]pyrene, B[a]P; 3-nitrobenzanthrone, 3-NBA) and EOM from PM <2.5 μm (PM2.5). ROS levels were evaluated at 8 time intervals (30 min-24 h). In both cell lines, B[a]P treatment was associated with a time-dependent decrease of ROS levels. This trend was more pronounced in HEL12469 cells and was accompanied by increased TAC. A similar response was observed upon 3-NBA treatment in HEL12469 cells. In A549 cells, however, this compound significantly increased superoxide levels. This response was accompanied by the decrease of TAC as well as HMOX1 and TXNRD1 expression. In both cell lines, a short-time exposure to EOMs tended to increase ROS levels, while a marked decrease was observed after longer treatment periods. This was accompanied by the induction of HMOX1 and TXNRD1 expression in HEL12469 cells and increased TAC in A549 cells. In summary, our data indicate that in the studied cell lines B[a]P and EOMs caused a time-dependent decrease of intracellular ROS levels, probably due to the activation of the antioxidant response. This response was not detected in A549 cells following 3-NBA treatment, which acted as a strong superoxide inducer. Pro-oxidant properties of EOMs are limited to short-time exposure periods. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of a beta-adrenergic blocking agent timolol on intra ocular pressure responses induced by stimulation of cervical sympathetic nerve in the cat.

PubMed

Naito, A; Izumi, H; Karita, K; Tamai, M

2001-12-01

We clarified whether the intraocular pressure (IOP) response elicited by stimulation of the cervical sympathetic nerve (CSN) is influenced by changes in the baseline of IOP level and by beta-adrenergic blockade. The CSN was stimulated electrically for 30 seconds (10 V, 0.1-100 Hz, 2 milliseconds pulse duration) in urethane (100 mg/kg i.v.)-chloralose (50 mg/kg i.v.)-anesthetized, paralyzed cats. The IOP was monitored manometrically, and a controlled saline infusion was delivered into the anterior chamber to gradually increase IOP. CSN stimulation was delivered at the various baseline IOP levels so obtained. When required, a beta-adrenergic blocker timolol (2%) was delivered into the conjunctival cul-de-sac. The normal IOP in our cats was 25+/-3 mmHg. This value decreased transiently on CSN stimulation. The amplitude of this IOP response depended on stimulus frequency and the pre-stimulus baseline IOP level. Topical administration of timolol increased the IOP response to CSN stimulation at a given baseline level. These results suggest that beta-adrenergic blockade increases the alpha-adrenergic mediated-IOP reduction elicited by CSN stimulation at given baseline IOP level.

Stress and cortisol responses in men: differences according to facial symmetry.

PubMed

Borráz-León, Javier I; Cerda-Molina, Ana Lilia; Mayagoitia-Novales, Lilian

2017-11-01

Stress response is associated with increased activity in the hypothalamic-pituitary-adrenocortical axis. Chronic stress-induced elevation in cortisol may alter its own negative regulation with multiple long-term consequences for physical and psychological health. One of the most reliable physical traits associated with mental, apparent physical health, and competitiveness is the degree of facial fluctuating asymmetry. However, to our knowledge there are no studies regarding the relationship between cortisol levels, facial symmetry and male competitiveness, and how cortisol changes after a stressful test depending on these traits. Here, a group of 100 college men were photographed to obtain their facial asymmetry levels. They then, answered the perceived stress scale and the intrasexual competition test and donated two saliva samples (pre-and post-test sample) to measure the change in their cortisol levels after a stressful test. We found that basal cortisol levels were positively correlated with both perceived stress and competitiveness, but not with facial fluctuating asymmetry. Cortisol levels increased in most symmetrical men after a short stressful test, but it decreased in most asymmetrical men. The results suggest differences in endocrine responses according to facial fluctuating asymmetry in men and how these responses could be related to the maintenance of social status.

Temporal variations in Global Seismic Stations ambient noise power levels

USGS Publications Warehouse

Ringler, A.T.; Gee, L.S.; Hutt, C.R.; McNamara, D.E.

2010-01-01

Recent concerns about time-dependent response changes in broadband seismometers have motivated the need for methods to monitor sensor health at Global Seismographic Network (GSN) stations. We present two new methods for monitoring temporal changes in data quality and instrument response transfer functions that are independent of Earth seismic velocity and attenuation models by comparing power levels against different baseline values. Our methods can resolve changes in both horizontal and vertical components in a broad range of periods (∼0.05 to 1,000 seconds) in near real time. In this report, we compare our methods with existing techniques and demonstrate how to resolve instrument response changes in long-period data (>100 seconds) as well as in the microseism bands (5 to 20 seconds).

Functional Macroautophagy Induction by Influenza A Virus without a Contribution to Major Histocompatibility Complex Class II-Restricted Presentation▿†

PubMed Central

Comber, Joseph D.; Robinson, Tara M.; Siciliano, Nicholas A.; Snook, Adam E.; Eisenlohr, Laurence C.

2011-01-01

Major histocompatibility complex (MHC) class II-presented peptides can be derived from both exogenous (extracellular) and endogenous (biosynthesized) sources of antigen. Although several endogenous antigen-processing pathways have been reported, little is known about their relative contributions to global CD4+ T cell responses against complex antigens. Using influenza virus for this purpose, we assessed the role of macroautophagy, a process in which cytosolic proteins are delivered to the lysosome by de novo vesicle formation and membrane fusion. Influenza infection triggered productive macroautophagy, and autophagy-dependent presentation was readily observed with model antigens that naturally traffic to the autophagosome. Furthermore, treatments that enhance or inhibit macroautophagy modulated the level of presentation from these model antigens. However, validated enzyme-linked immunospot (ELISpot) assays of influenza-specific CD4+ T cells from infected mice using a variety of antigen-presenting cells, including primary dendritic cells, revealed no detectable macroautophagy-dependent component. In contrast, the contribution of proteasome-dependent endogenous antigen processing to the global influenza CD4+ response was readily appreciated. The contribution of macroautophagy to the MHC class II-restricted response may vary depending upon the pathogen. PMID:21525345

The Simon effect in action: planning and/or on-line control effects?

PubMed

Scorolli, Claudia; Pellicano, Antonello; Nicoletti, Roberto; Rubichi, Sandro; Castiello, Umberto

2015-07-01

Choice reaction tasks are performed faster when stimulus location corresponds to response location (Simon effect). This spatial stimulus-response compatibility effect affects performance at the level of action planning and execution. However, when response selection is completed before movement initiation, the Simon effect arises only at the planning level. The aim of this study was to ascertain whether when a precocious response selection is requested, the Simon effect can be detected on the kinematics characterizing the online control phase of a non-ballistic movement. Participants were presented with red or green colored squares, which could appear on the right, left, above, or below a central cross. Depending on the square's color, participants had to release one of two buttons (right/left), then reach toward and press a corresponding lateral pad. We found evidence of the Simon effect on both action planning and on-line control. Moreover, the investigation of response conflict at the level of previous trials (i.e., n-1), a factor that might determine interference at the level of the current response, revealed a conflict adaptation process across trials. Results are discussed in terms of current theories concerned with the Simon effect and the distinction between action planning and control. Copyright © 2014 Cognitive Science Society, Inc.

Subgap time of flight: A spectroscopic study of deep levels in semi-insulating CdTe:Cl

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

Pousset, J.; Farella, I.; Cola, A., E-mail: adriano.cola@le.imm.cnr.it

2016-03-14

We report on a study of deep levels in semi-insulating CdTe:Cl by means of a time-of-flight spectral approach. By varying the wavelength of a pulsed optical source within the CdTe energy gap, transitions to/from localized levels generate free carriers which are analysed through the induced photocurrent transients. Both acceptor-like centers, related to the A-center, and a midgap level, 0.725 eV from the valence band, have been detected. The midgap level is close to the Fermi level and is possibly a recombination center responsible for the compensation mechanism. When the irradiance is varied, either linear or quadratic dependence of the electron andmore » hole collected charge are observed, depending on the dominant optical transitions. The analysis discloses the potentiality of such a novel approach exploitable in the field of photorefractive materials as well as for deep levels spectroscopy.« less

Sex differences in associations between cannabis craving and neural responses to cannabis cues: Implications for treatment.

PubMed

Wetherill, Reagan R; Jagannathan, Kanchana; Hager, Nathan; Childress, Anna Rose; Franklin, Teresa R

2015-08-01

Preclinical and clinical research indicates that there are sex differences in how men and women initiate, progress, respond to, and withdraw from cannabis use; however, neurophysiological differences, such as neural responses to cannabis cues, are not well understood. Using functional MRI and an event-related blood oxygen level-dependent backward-masking task, we compared neural responses to backward-masked cannabis cues to neutral cues in treatment-seeking, cannabis-dependent adults (N = 44; 27 males) and examined whether sex differences exist. In addition, functional MRI findings were correlated with cannabis craving. Backward-masked cannabis cues elicited greater neural responses than neutral cues in reward-related brain regions, including the striatum, hippocampus/amygdala, insula, anterior cingulate cortex, and lateral orbitofrontal cortex, p < .01, k > 121 voxels. Although no significant sex differences in neural responses to cannabis cues emerged, women showed a positive correlation between neural responses to cannabis cues in the bilateral insula and cannabis craving and an inverse correlation between neural responses to cannabis cues in the left lateral orbitofrontal cortex and cannabis craving. Men, however, showed a positive correlation between neural responses to cannabis cues in the striatum and cannabis craving. Given that cues and craving are important triggers and the focus on many behavioral treatment approaches, these findings suggest that treatment-seeking, cannabis-dependent men and women may benefit from sex-specific and tailored cannabis use disorder treatments. (c) 2015 APA, all rights reserved).

Amino Acid Change in the Carbohydrate Response Element Binding Protein is associated with lower triglycerides and myocardial infarction incidence depending on level of adherence to the Mediterranean diet in the PREDIMED trial

USDA-ARS?s Scientific Manuscript database

A variant (rs3812316, C771G, and Gln241His) in the MLXIPL (Max-like protein X interacting protein-like) gene encoding the carbohydrate response element binding protein has been associated with lower triglycerides. However, its association with cardiovascular diseases and gene-diet interactions modul...

Abscisic acid regulates root growth under osmotic stress conditions via an interacting hormonal network with cytokinin, ethylene and auxin.

PubMed

Rowe, James H; Topping, Jennifer F; Liu, Junli; Lindsey, Keith

2016-07-01

Understanding the mechanisms regulating root development under drought conditions is an important question for plant biology and world agriculture. We examine the effect of osmotic stress on abscisic acid (ABA), cytokinin and ethylene responses and how they mediate auxin transport, distribution and root growth through effects on PIN proteins. We integrate experimental data to construct hormonal crosstalk networks to formulate a systems view of root growth regulation by multiple hormones. Experimental analysis shows: that ABA-dependent and ABA-independent stress responses increase under osmotic stress, but cytokinin responses are only slightly reduced; inhibition of root growth under osmotic stress does not require ethylene signalling, but auxin can rescue root growth and meristem size; osmotic stress modulates auxin transporter levels and localization, reducing root auxin concentrations; PIN1 levels are reduced under stress in an ABA-dependent manner, overriding ethylene effects; and the interplay among ABA, ethylene, cytokinin and auxin is tissue-specific, as evidenced by differential responses of PIN1 and PIN2 to osmotic stress. Combining experimental analysis with network construction reveals that ABA regulates root growth under osmotic stress conditions via an interacting hormonal network with cytokinin, ethylene and auxin. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

The regulation of TNFα production after heat and endotoxin stimulation is dependent on Annexin-A1 and HSP70.

PubMed

Nair, Sunitha; Arora, Suruchi; Lim, Jyue Yuan; Lee, Lay Hoon; Lim, Lina H K

2015-07-01

Febrile temperatures can induce stress responses which protect cells from damage and can reduce inflammation during infections and sepsis. However, the mechanisms behind the protective functions of heat in response to the bacterial endotoxin LPS are unclear. We have recently shown that Annexin-1 (ANXA1)-deficient macrophages exhibited higher TNFα levels after LPS stimulation. Moreover, we have previously reported that ANXA1 can function as a stress protein. Therefore in this study, we determined if ANXA1 is involved in the protective effects of heat on cytokine levels in macrophages after heat and LPS. Exposure of macrophages to 42 °C for 1 h prior to LPS results in an inhibition of TNFα production, which was not evident in ANXA1(-/-) macrophages. We show that this regulation involves primarily MYD88-independent pathways. ANXA1 regulates TNFα mRNA stability after heat and LPS, and this is dependent on endogenous ANXA1 expression and not exogenously secreted factors. Further mechanistic studies revealed the possible involvement of the heat shock protein HSP70 and JNK in the heat and inflammatory stress response regulated by ANXA1. This study shows that ANXA1, an immunomodulatory protein, is critical in the heat stress response induced after heat and endotoxin stimulation.

Estimating of aquifer parameters from the single-well water-level measurements in response to advancing longwall mine by using particle swarm optimization

NASA Astrophysics Data System (ADS)

Buyuk, Ersin; Karaman, Abdullah

2017-04-01

We estimated transmissivity and storage coefficient values from the single well water-level measurements positioned ahead of the mining face by using particle swarm optimization (PSO) technique. The water-level response to the advancing mining face contains an semi-analytical function that is not suitable for conventional inversion shemes because the partial derivative is difficult to calculate . Morever, the logaritmic behaviour of the model create difficulty for obtaining an initial model that may lead to a stable convergence. The PSO appears to obtain a reliable solution that produce a reasonable fit between water-level data and model function response. Optimization methods have been used to find optimum conditions consisting either minimum or maximum of a given objective function with regard to some criteria. Unlike PSO, traditional non-linear optimization methods have been used for many hydrogeologic and geophysical engineering problems. These methods indicate some difficulties such as dependencies to initial model, evolution of the partial derivatives that is required while linearizing the model and trapping at local optimum. Recently, Particle swarm optimization (PSO) became the focus of modern global optimization method that is inspired from the social behaviour of birds of swarms, and appears to be a reliable and powerful algorithms for complex engineering applications. PSO that is not dependent on an initial model, and non-derivative stochastic process appears to be capable of searching all possible solutions in the model space either around local or global optimum points.

Two Prospective Studies of Changes in Stress Generation across Depressive Episodes in Adolescents and Emerging Adults

PubMed Central

Morris, Matthew C.; Kouros, Chrystyna D.; Hellman, Natalie; Rao, Uma; Garber, Judy

2014-01-01

The stress generation hypothesis was tested in two different longitudinal studies examining relations between weekly depression symptom ratings and stress levels in adolescents and emerging adults at varied risk for depression. Participants in Study 1 included 240 adolescents who differed with regard to their mother’s history of depressive disorders. Youth were assessed annually across 6 years (Grades 6 through 12). Consistent with the depression autonomy model, higher numbers of prior major depressive episodes (MDEs) were associated with weaker stress generation effects, such that higher levels of depressive symptoms predicted increases in levels of dependent stressors for adolescents with ≤ 2 prior MDEs, but depressive symptoms were not significantly related to dependent stress levels for youth with ≥ 3 prior MDEs. In Study 2, participants were 32 remitted-depressed and 36 never-depressed young adults who completed a psychosocial stress task to determine cortisol reactivity and were re-assessed for depression and stress approximately eight months later. Stress generation effects were moderated by cortisol responses to a laboratory psychosocial stressor, such that individuals with higher cortisol responses exhibited a pattern consistent with the depression autonomy model, whereas individuals with lower cortisol responses showed a pattern more consistent with the depression sensitization model. Finally, comparing across the two samples, stress generation effects were weaker for older participants and for those with more prior MDEs. The complex, multi-factorial relation between stress and depression is discussed. PMID:25422968

Interactions of cortisol, testosterone, and resistance training: influence of circadian rhythms.

PubMed

Hayes, Lawrence D; Bickerstaff, Gordon F; Baker, Julien S

2010-06-01

Diurnal variation of sports performance usually peaks in the late afternoon, coinciding with increased body temperature. This circadian pattern of performance may be explained by the effect of increased core temperature on peripheral mechanisms, as neural drive does not appear to exhibit nycthemeral variation. This typical diurnal regularity has been reported in a variety of physical activities spanning the energy systems, from Adenosine triphosphate-phosphocreatine (ATP-PC) to anaerobic and aerobic metabolism, and is evident across all muscle contractions (eccentric, isometric, concentric) in a large number of muscle groups. Increased nerve conduction velocity, joint suppleness, increased muscular blood flow, improvements of glycogenolysis and glycolysis, increased environmental temperature, and preferential meteorological conditions may all contribute to diurnal variation in physical performance. However, the diurnal variation in strength performance can be blunted by a repeated-morning resistance training protocol. Optimal adaptations to resistance training (muscle hypertrophy and strength increases) also seem to occur in the late afternoon, which is interesting, since cortisol and, particularly, testosterone (T) concentrations are higher in the morning. T has repeatedly been linked with resistance training adaptation, and higher concentrations appear preferential. This has been determined by suppression of endogenous production and exogenous supplementation. However, the cortisol (C)/T ratio may indicate the catabolic/anabolic environment of an organism due to their roles in protein degradation and protein synthesis, respectively. The morning elevated T level (seen as beneficial to achieve muscle hypertrophy) may be counteracted by the morning elevated C level and, therefore, protein degradation. Although T levels are higher in the morning, an increased resistance exercise-induced T response has been found in the late afternoon, suggesting greater responsiveness of the hypothalamo-pituitary-testicular axis then. Individual responsiveness has also been observed, with some participants experiencing greater hypertrophy and strength increases in response to strength protocols, whereas others respond preferentially to power, hypertrophy, or strength endurance protocols dependent on which protocol elicited the greatest T response. It appears that physical performance is dependent on a number of endogenous time-dependent factors, which may be masked or confounded by exogenous circadian factors. Strength performance without time-of-day-specific training seems to elicit the typical diurnal pattern, as does resistance training adaptations. The implications for this are (a) athletes are advised to coincide training times with performance times, and (b) individuals may experience greater hypertrophy and strength gains when resistance training protocols are designed dependent on individual T response.

Self-Management as a Class-Wide Intervention: An Evaluation of the "Self & Match" System Embedded within a Dependent Group Contingency

ERIC Educational Resources Information Center

Bulla, Andrew J.; Frieder, Jessica E.

2018-01-01

Teachers are responsible for providing an education to students of all ability levels. Recent data suggest that roughly 95% of students with a disability are receiving some form of education in their general education setting. Individuals with disabilities tend to engage in higher levels of disruptive behaviors (e.g., talking out in class,…

Multivariate pattern dependence

PubMed Central

Saxe, Rebecca

2017-01-01

When we perform a cognitive task, multiple brain regions are engaged. Understanding how these regions interact is a fundamental step to uncover the neural bases of behavior. Most research on the interactions between brain regions has focused on the univariate responses in the regions. However, fine grained patterns of response encode important information, as shown by multivariate pattern analysis. In the present article, we introduce and apply multivariate pattern dependence (MVPD): a technique to study the statistical dependence between brain regions in humans in terms of the multivariate relations between their patterns of responses. MVPD characterizes the responses in each brain region as trajectories in region-specific multidimensional spaces, and models the multivariate relationship between these trajectories. We applied MVPD to the posterior superior temporal sulcus (pSTS) and to the fusiform face area (FFA), using a searchlight approach to reveal interactions between these seed regions and the rest of the brain. Across two different experiments, MVPD identified significant statistical dependence not detected by standard functional connectivity. Additionally, MVPD outperformed univariate connectivity in its ability to explain independent variance in the responses of individual voxels. In the end, MVPD uncovered different connectivity profiles associated with different representational subspaces of FFA: the first principal component of FFA shows differential connectivity with occipital and parietal regions implicated in the processing of low-level properties of faces, while the second and third components show differential connectivity with anterior temporal regions implicated in the processing of invariant representations of face identity. PMID:29155809

Periodic and chaotic psychological stress variations as predicted by a social support buffered response model

NASA Astrophysics Data System (ADS)

Field, Richard J.; Gallas, Jason A. C.; Schuldberg, David

2017-08-01

Recent work has introduced social dynamic models of people's stress-related processes, some including amelioration of stress symptoms by support from others. The effects of support may be ;direct;, depending only on the level of support, or ;buffering;, depending on the product of the level of support and level of stress. We focus here on the nonlinear buffering term and use a model involving three variables (and 12 control parameters), including stress as perceived by the individual, physical and psychological symptoms, and currently active social support. This model is quantified by a set of three nonlinear differential equations governing its stationary-state stability, temporal evolution (sometimes oscillatory), and how each variable affects the others. Chaos may appear with periodic forcing of an environmental stress parameter. Here we explore this model carefully as the strength and amplitude of this forcing, and an important psychological parameter relating to self-kindling in the stress response, are varied. Three significant observations are made: 1. There exist many complex but orderly regions of periodicity and chaos, 2. there are nested regions of increasing number of peaks per cycle that may cascade to chaos, and 3. there are areas where more than one state, e.g., a period-2 oscillation and chaos, coexist for the same parameters; which one is reached depends on initial conditions.

Redox system and phospholipid metabolism in the kidney of hypertensive rats after FAAH inhibitor URB597 administration.

PubMed

Biernacki, Michał; Ambrożewicz, Ewa; Gęgotek, Agnieszka; Toczek, Marek; Bielawska, Katarzyna; Skrzydlewska, Elżbieta

2018-05-01

Primary and secondary hypertension is associated with kidney redox imbalance resulting in enhanced reactive oxygen species (ROS) and enzymes dependent phospholipid metabolism. The fatty acid amide hydrolase inhibitor, URB597, modulates the levels of endocannabinoids, particularly of anandamide, which is responsible for controlling blood pressure and regulating redox balance. Therefore, this study aimed to compare the effects of chronic URB597 administration to spontaneously hypertensive rats (SHR) and rats with secondary hypertension (DOCA-salt rats) on the kidney metabolism associated with the redox and endocannabinoid systems. It was shown fatty acid amide hydrolase (FAAH) inhibitor decreased the activity of ROS-generated enzymes what resulted in a reduction of ROS level. Moreover varied changes in antioxidant parameters were observed with tendency to improve antioxidant defense in SHR kidney. Moreover, URB597 administration to hypertensive rats decreased pro-inflammatory response, particularly in the kidneys of DOCA-salt hypertensive rats. URB597 had tendency to enhance ROS-dependent phospholipid oxidation, estimated by changes in neuroprostanes in the kidney of SHR and reactive aldehydes (4-hydroxynonenal and malondialdehyde) in DOCA-salt rats, in particular. The administration of FAAH inhibitor resulted in increased level of endocannabinoids in kidney of both groups of hypertensive rats led to enhanced expression of the cannabinoid receptors type 1 and 2 in SHR as well as vanilloid receptor 1 receptors in DOCA-salt rats. URB597 given to normotensive rats also affected kidney oxidative metabolism, resulting in enhanced level of neuroprostanes in Wistar Kyoto rats and reactive aldehydes in Wistar rats. Moreover, the level of endocannabinoids and cannabinoid receptors were significantly higher in both control groups of rats after URB597 administration. In conclusion, because URB597 disturbed the kidney redox system and phospholipid ROS-dependent and enzymatic-dependent metabolism, the administration of this inhibitor may enhance kidney disorders depending on model of hypertension, but may also cause kidney disturbances in control rats. Therefore, further studies are warranted. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Social interaction with a tutor modulates responsiveness of specific auditory neurons in juvenile zebra finches.

PubMed

Yanagihara, Shin; Yazaki-Sugiyama, Yoko

2018-04-12

Behavioral states of animals, such as observing the behavior of a conspecific, modify signal perception and/or sensations that influence state-dependent higher cognitive behavior, such as learning. Recent studies have shown that neuronal responsiveness to sensory signals is modified when animals are engaged in social interactions with others or in locomotor activities. However, how these changes produce state-dependent differences in higher cognitive function is still largely unknown. Zebra finches, which have served as the premier songbird model, learn to sing from early auditory experiences with tutors. They also learn from playback of recorded songs however, learning can be greatly improved when song models are provided through social communication with tutors (Eales, 1989; Chen et al., 2016). Recently we found a subset of neurons in the higher-level auditory cortex of juvenile zebra finches that exhibit highly selective auditory responses to the tutor song after song learning, suggesting an auditory memory trace of the tutor song (Yanagihara and Yazaki-Sugiyama, 2016). Here we show that auditory responses of these selective neurons became greater when juveniles were paired with their tutors, while responses of non-selective neurons did not change. These results suggest that social interaction modulates cortical activity and might function in state-dependent song learning. Copyright © 2018 Elsevier B.V. All rights reserved.

A Full Dynamic Compound Inverse Method for output-only element-level system identification and input estimation from earthquake response signals

NASA Astrophysics Data System (ADS)

Pioldi, Fabio; Rizzi, Egidio

2016-08-01

This paper proposes a new output-only element-level system identification and input estimation technique, towards the simultaneous identification of modal parameters, input excitation time history and structural features at the element-level by adopting earthquake-induced structural response signals. The method, named Full Dynamic Compound Inverse Method (FDCIM), releases strong assumptions of earlier element-level techniques, by working with a two-stage iterative algorithm. Jointly, a Statistical Average technique, a modification process and a parameter projection strategy are adopted at each stage to achieve stronger convergence for the identified estimates. The proposed method works in a deterministic way and is completely developed in State-Space form. Further, it does not require continuous- to discrete-time transformations and does not depend on initialization conditions. Synthetic earthquake-induced response signals from different shear-type buildings are generated to validate the implemented procedure, also with noise-corrupted cases. The achieved results provide a necessary condition to demonstrate the effectiveness of the proposed identification method.

Evaluation of Effective Sources in Uncertainty Measurements of Personal Dosimetry by a Harshaw TLD System

PubMed Central

Hosseini Pooya, SM; Orouji, T

2014-01-01

Background: The accurate results of the individual doses in personal dosimety which are reported by the service providers in personal dosimetry are very important. There are national / international criteria for acceptable dosimetry system performance. Objective: In this research, the sources of uncertainties are identified, measured and calculated in a personal dosimetry system by TLD. Method: These sources are included; inhomogeneity of TLDs sensitivity, variability of TLD readings due to limited sensitivity and background, energy dependence, directional dependence, non-linearity of the response, fading, dependent on ambient temperature / humidity and calibration errors, which may affect on the dose responses. Some parameters which influence on the above sources of uncertainty are studied for Harshaw TLD-100 cards dosimeters as well as the hot gas Harshaw 6600 TLD reader system. Results: The individual uncertainties of each sources was measured less than 6.7% in 68% confidence level. The total uncertainty was calculated 17.5% with 95% confidence level. Conclusion: The TLD-100 personal dosimeters as well as the Harshaw TLD-100 reader 6600 system show the total uncertainty value which is less than that of admissible value of 42% for personal dosimetry services. PMID:25505769

Feedbacks between inundation, root production, and shoot growth in a rapidly submerging brackish marsh

USGS Publications Warehouse

Kirwan, Matthew L.; Guntenspergen, Glenn R.

2012-01-01

6.Synthesis. Below-ground responses of marshes to sea level rise are more broadly applicable than above-ground feedbacks because they are consistent among different species and do not depend on the availability of mineral sediment.

Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies

PubMed Central

Lee, Wei-Hua; Higuchi, Hitoshi; Ikeda, Sakae; Macke, Erica L; Takimoto, Tetsuya; Pattnaik, Bikash R; Liu, Che; Chu, Li-Fang; Siepka, Sandra M; Krentz, Kathleen J; Rubinstein, C Dustin; Kalejta, Robert F; Thomson, James A; Mullins, Robert F; Takahashi, Joseph S; Pinto, Lawrence H; Ikeda, Akihiro

2016-01-01

While the aging process is central to the pathogenesis of age-dependent diseases, it is poorly understood at the molecular level. We identified a mouse mutant with accelerated aging in the retina as well as pathologies observed in age-dependent retinal diseases, suggesting that the responsible gene regulates retinal aging, and its impairment results in age-dependent disease. We determined that a mutation in the transmembrane 135 (Tmem135) is responsible for these phenotypes. We observed localization of TMEM135 on mitochondria, and imbalance of mitochondrial fission and fusion in mutant Tmem135 as well as Tmem135 overexpressing cells, indicating that TMEM135 is involved in the regulation of mitochondrial dynamics. Additionally, mutant retina showed higher sensitivity to oxidative stress. These results suggest that the regulation of mitochondrial dynamics through TMEM135 is critical for protection from environmental stress and controlling the progression of retinal aging. Our study identified TMEM135 as a critical link between aging and age-dependent diseases. DOI: http://dx.doi.org/10.7554/eLife.19264.001 PMID:27863209

Progress in implementation of WHO FCTC Article 14 and its guidelines: a survey of tobacco dependence treatment provision in 142 countries.

PubMed

Nilan, Kapka; Raw, Martin; McKeever, Tricia M; Murray, Rachael L; McNeill, Ann

2017-11-01

To (1) estimate the number of Parties to the Framework Convention on Tobacco Control (FCTC) providing tobacco dependence treatment in accordance with the recommendations of Article 14 and its guidelines; (2) assess association between provision and countries' income level; and (3) assess progress over time. Cross-sectional study. Online survey from December 2014 to July 2015. Contacts in 172 countries were surveyed, representing 169 of the 180 FCTC Parties at the time of the survey. A 26-item questionnaire based on the Article 14 recommendations including tobacco treatment infrastructure and cessation support systems. Progress over time was assessed for those countries that also participated in our 2012 survey and did not change country income level classification. We received responses from contacts in 142 countries, an 83% response rate. Overall, 54% of respondents reported that their country had an officially identified person responsible for tobacco dependence treatment, 32% an official national treatment strategy, 40% official national treatment guidelines, 25% a clearly identified budget for treatment, 17% text messaging, 23% free national quitlines and 26% specialized treatment services. Most measures were associated positively and significantly with countries' income level (P < 0.001). Measures not associated significantly with income level included mandatory recording of tobacco use (30% of countries), offering help to health-care workers (HCW) to stop using tobacco (44%), brief advice integrated into existing services (44%), and training HCW to give brief advice (81%). Reporting having an officially identified person responsible for tobacco cessation was the only measure with a statistically significant improvement over time (P = 0.0351). Fewer than half of countries that are Parties to the Framework Convention on Tobacco Control have implemented the recommendations of Article 14 and its guidelines, and for most measures, provision was greater the higher the country's income. There was little improvement in treatment provision between 2012 and 2015 in all countries. © 2017 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Sound-level-dependent representation of frequency modulations in human auditory cortex: a low-noise fMRI study.

PubMed

Brechmann, André; Baumgart, Frank; Scheich, Henning

2002-01-01

Recognition of sound patterns must be largely independent of level and of masking or jamming background sounds. Auditory patterns of relevance in numerous environmental sounds, species-specific vocalizations and speech are frequency modulations (FM). Level-dependent activation of the human auditory cortex (AC) in response to a large set of upward and downward FM tones was studied with low-noise (48 dB) functional magnetic resonance imaging at 3 Tesla. Separate analysis in four territories of AC was performed in each individual brain using a combination of anatomical landmarks and spatial activation criteria for their distinction. Activation of territory T1b (including primary AC) showed the most robust level dependence over the large range of 48-102 dB in terms of activated volume and blood oxygen level dependent contrast (BOLD) signal intensity. The left nonprimary territory T2 also showed a good correlation of level with activated volume but, in contrast to T1b, not with BOLD signal intensity. These findings are compatible with level coding mechanisms observed in animal AC. A systematic increase of activation with level was not observed for T1a (anterior of Heschl's gyrus) and T3 (on the planum temporale). Thus these areas might not be specifically involved in processing of the overall intensity of FM. The rostral territory T1a of the left hemisphere exhibited highest activation when the FM sound level fell 12 dB below scanner noise. This supports the previously suggested special involvement of this territory in foreground-background decomposition tasks. Overall, AC of the left hemisphere showed a stronger level-dependence of signal intensity and activated volume than the right hemisphere. But any side differences of signal intensity at given levels were lateralized to right AC. This might point to an involvement of the right hemisphere in more specific aspects of FM processing than level coding.

Changes in pitch height elicit both language universal and language dependent changes in neural representation of pitch in the brainstem and auditory cortex

PubMed Central

Krishnan, Ananthanarayan; Suresh, Chandan H.; Gandour, Jackson T.

2017-01-01

Language experience shapes encoding of pitch-relevant information at both brainstem and cortical levels of processing. Pitch height is a salient dimension that orders pitch from low to high. Herein we investigate the effects of language experience (Chinese, English) in the brainstem and cortex on i) neural responses to variations in pitch height, ii) presence of asymmetry in cortical pitch representation, and iii) patterns of relative changes in magnitude of pitch height between these two levels of brain structure. Stimuli were three nonspeech homologs of Mandarin Tone 2 varying in pitch height only. The frequency-following response (FFR) and the cortical pitch-specific response (CPR) were recorded concurrently. At the Fz-linked T7/T8 site, peak latency of Na, Pb, and Nb decreased with increasing pitch height for both groups. Peak-to-peak amplitude of Na–Pb and Pb–Nb increased with increasing pitch height across groups. A language-dependent effect was restricted to Na-Pb; the Chinese had larger amplitude than the English group. At temporal sites (T7/T8), the Chinese group had larger amplitude, as compared to English, across stimuli, but also limited to the Na-Pb component and right temporal site. In the brainstem, F0 magnitude decreased with increasing pitch height; Chinese had larger magnitude across stimuli. A comparison of CPR and FFR responses revealed distinct patterns of relative changes in magnitude common to both groups. CPR amplitude increased and FFR amplitude decreased with increasing pitch height. Experience-dependent effects on CPR components vary as a function of neural sensitivity to pitch height within a particular temporal window (Na–Pb). Differences between the auditory brainstem and cortex imply distinct neural mechanisms for pitch extraction at both levels of brain structure. PMID:28108254

Changes in pitch height elicit both language-universal and language-dependent changes in neural representation of pitch in the brainstem and auditory cortex.

PubMed

Krishnan, Ananthanarayan; Suresh, Chandan H; Gandour, Jackson T

2017-03-27

Language experience shapes encoding of pitch-relevant information at both brainstem and cortical levels of processing. Pitch height is a salient dimension that orders pitch from low to high. Herein we investigate the effects of language experience (Chinese, English) in the brainstem and cortex on (i) neural responses to variations in pitch height, (ii) presence of asymmetry in cortical pitch representation, and (iii) patterns of relative changes in magnitude of pitch height between these two levels of brain structure. Stimuli were three nonspeech homologs of Mandarin Tone 2 varying in pitch height only. The frequency-following response (FFR) and the cortical pitch-specific response (CPR) were recorded concurrently. At the Fz-linked T7/T8 site, peak latency of Na, Pb, and Nb decreased with increasing pitch height for both groups. Peak-to-peak amplitude of Na-Pb and Pb-Nb increased with increasing pitch height across groups. A language-dependent effect was restricted to Na-Pb; the Chinese had larger amplitude than the English group. At temporal sites (T7/T8), the Chinese group had larger amplitude, as compared to English, across stimuli, but also limited to the Na-Pb component and right temporal site. In the brainstem, F0 magnitude decreased with increasing pitch height; Chinese had larger magnitude across stimuli. A comparison of CPR and FFR responses revealed distinct patterns of relative changes in magnitude common to both groups. CPR amplitude increased and FFR amplitude decreased with increasing pitch height. Experience-dependent effects on CPR components vary as a function of neural sensitivity to pitch height within a particular temporal window (Na-Pb). Differences between the auditory brainstem and cortex imply distinct neural mechanisms for pitch extraction at both levels of brain structure. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Temporal response of hydraulic head, temperature, and chloride concentrations to sea-level changes, Floridan aquifer system, USA

NASA Astrophysics Data System (ADS)

Hughes, J. D.; Vacher, H. L.; Sanford, Ward E.

2009-06-01

Three-dimensional density-dependent flow and transport modeling of the Floridan aquifer system, USA shows that current chloride concentrations are not in equilibrium with current sea level and, second, that the geometric configuration of the aquifer has a significant effect on system responses. The modeling shows that hydraulic head equilibrates first, followed by temperatures, and then by chloride concentrations. The model was constructed using a modified version of SUTRA capable of simulating multi-species heat and solute transport, and was compared to pre-development conditions using hydraulic heads, chloride concentrations, and temperatures from 315 observation wells. Three hypothetical, sinusoidal sea-level changes occurring over 100,000 years were used to evaluate how the simulated aquifer responds to sea-level changes. Model results show that hydraulic head responses lag behind sea-level changes only where the Miocene Hawthorn confining unit is thick and represents a significant restriction to flow. Temperatures equilibrate quickly except where the Hawthorn confining unit is thick and the duration of the sea-level event is long (exceeding 30,000 years). Response times for chloride concentrations to equilibrate are shortest near the coastline and where the aquifer is unconfined; in contrast, chloride concentrations do not change significantly over the 100,000-year simulation period where the Hawthorn confining unit is thick.

Oxygen Level and LFP in Task-Positive and Task-Negative Areas: Bridging BOLD fMRI and Electrophysiology.

PubMed

Bentley, William J; Li, Jingfeng M; Snyder, Abraham Z; Raichle, Marcus E; Snyder, Lawrence H

2016-01-01

The human default mode network (DMN) shows decreased blood oxygen level dependent (BOLD) signals in response to a wide range of attention-demanding tasks. Our understanding of the specifics regarding the neural activity underlying these "task-negative" BOLD responses remains incomplete. We paired oxygen polarography, an electrode-based oxygen measurement technique, with standard electrophysiological recording to assess the relationship of oxygen and neural activity in task-negative posterior cingulate cortex (PCC), a hub of the DMN, and visually responsive task-positive area V3 in the awake macaque. In response to engaging visual stimulation, oxygen, LFP power, and multi-unit activity in PCC showed transient activation followed by sustained suppression. In V3, oxygen, LFP power, and multi-unit activity showed an initial phasic response to the stimulus followed by sustained activation. Oxygen responses were correlated with LFP power in both areas, although the apparent hemodynamic coupling between oxygen level and electrophysiology differed across areas. Our results suggest that oxygen responses reflect changes in LFP power and multi-unit activity and that either the coupling of neural activity to blood flow and metabolism differs between PCC and V3 or computing a linear transformation from a single LFP band to oxygen level does not capture the true physiological process. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Perceptual conflict during sensorimotor integration processes - a neurophysiological study in response inhibition.

PubMed

Chmielewski, Witold X; Beste, Christian

2016-05-25

A multitude of sensory inputs needs to be processed during sensorimotor integration. A crucial factor for detecting relevant information is its complexity, since information content can be conflicting at a perceptual level. This may be central to executive control processes, such as response inhibition. This EEG study aims to investigate the system neurophysiological mechanisms behind effects of perceptual conflict on response inhibition. We systematically modulated perceptual conflict by integrating a Global-local task with a Go/Nogo paradigm. The results show that conflicting perceptual information, in comparison to non-conflicting perceptual information, impairs response inhibition performance. This effect was evident regardless of whether the relevant information for response inhibition is displayed on the global, or local perceptual level. The neurophysiological data suggests that early perceptual/ attentional processing stages do not underlie these modulations. Rather, processes at the response selection level (P3), play a role in changed response inhibition performance. This conflict-related impairment of inhibitory processes is associated with activation differences in (inferior) parietal areas (BA7 and BA40) and not as commonly found in the medial prefrontal areas. This suggests that various functional neuroanatomical structures may mediate response inhibition and that the functional neuroanatomical structures involved depend on the complexity of sensory integration processes.

Does Swimming at a Moderate Altitude Favor a Lower Oxidative Stress in an Intensity-Dependent Manner? Role of Nonenzymatic Antioxidants.

PubMed

Casuso, Rafael A; Aragón-Vela, Jerónimo; López-Contreras, Gracia; Gomes, Silvana N; Casals, Cristina; Barranco-Ruiz, Yaira; Mercadé, Jordi J; Huertas, Jesus R

2017-03-01

Casuso, Rafael A., Jerónimo Aragón-Vela, Gracia López-Contreras, Silvana N. Gomes, Cristina Casals, Yaira Barranco-Ruiz, Jordi J. Mercadé, and Jesus R. Huertas. Does swimming at a moderate altitude favor a lower oxidative stress in an intensity-dependent manner? Role of nonenzymatic antioxidants. High-Alt Med Biol. 18:46-55, 2017.-we aimed to describe oxidative damage and enzymatic and nonenzymatic antioxidant responses to swimming at different intensities in hypoxia. We recruited 12 highly experienced swimmers who have been involved in competitive swimming for at least 9 years. They performed a total of six swimming sessions carried out at low (LOW), moderate (MOD), or high (HIGH) intensity at low altitude (630 m) and at 2320 m above sea level. Blood samples were collected before the session (Pre), after the cool down (Post), and after 15 minutes of recovery (Rec). Blood lactate (BL) and heart rate were recorded throughout the main part of the session. Average velocities did not change between hypoxia and normoxia. We found a higher BL in response to MOD intensity in hypoxia. Plasmatic hydroperoxide level decreased at all intensities when swimming in hypoxia. This effect coincided with a lower glutation peroxidase activity and a marked mobilization of the circulating levels of α-tocopherol and coenzyme Q10 in an intensity-dependent manner. Our results suggest that, regardless of the intensity, no oxidative damage is found in response to hypoxic swimming in well-trained swimmers. Indeed, swimmers show a highly efficient antioxidant system by stimulating the mobilization of nonenzymatic antioxidants.

Contact-dependent growth inhibition induces high levels of antibiotic-tolerant persister cells in clonal bacterial populations.

PubMed

Ghosh, Anirban; Baltekin, Özden; Wäneskog, Marcus; Elkhalifa, Dina; Hammarlöf, Disa L; Elf, Johan; Koskiniemi, Sanna

2018-05-02

Bacterial populations can use bet-hedging strategies to cope with rapidly changing environments. One example is non-growing cells in clonal bacterial populations that are able to persist antibiotic treatment. Previous studies suggest that persisters arise in bacterial populations either stochastically through variation in levels of global signalling molecules between individual cells, or in response to various stresses. Here, we show that toxins used in contact-dependent growth inhibition (CDI) create persisters upon direct contact with cells lacking sufficient levels of CdiI immunity protein, which would otherwise bind to and neutralize toxin activity. CDI-mediated persisters form through a feedforward cycle where the toxic activity of the CdiA toxin increases cellular (p)ppGpp levels, which results in Lon-mediated degradation of the immunity protein and more free toxin. Thus, CDI systems mediate a population density-dependent bet-hedging strategy, where the fraction of non-growing cells is increased only when there are many cells of the same genotype. This may be one of the mechanisms of how CDI systems increase the fitness of their hosts. © 2018 The Authors.

Learning at different satiation levels reveals parallel functions for the cAMP-protein kinase A cascade in formation of long-term memory.

PubMed

Friedrich, Anke; Thomas, Ulf; Müller, Uli

2004-05-05

Learning and memory formation in intact animals is generally studied under defined parameters, including the control of feeding. We used associative olfactory conditioning of the proboscis extension response in honeybees to address effects of feeding status on processes of learning and memory formation. Comparing groups of animals with different but defined feeding status at the time of conditioning reveals new and characteristic features in memory formation. In animals fed 18 hr earlier, three-trial conditioning induces a stable memory that consists of different phases: a mid-term memory (MTM), translation-dependent early long-term memory (eLTM; 1-2 d), and a transcription-dependent late LTM (lLTM; > or =3 d). Additional feeding of a small amount of sucrose 4 hr before conditioning leads to a loss of all of these memory phases. Interestingly, the basal activity of the cAMP-dependent protein kinase A (PKA), a key player in LTM formation, differs in animals with different satiation levels. Pharmacological rescue of the low basal PKA activity in animals fed 4 hr before conditioning points to a specific function of cAMP-PKA cascade in mediating satiation-dependent memory formation. An increase in PKA activity during conditioning rescues only transcription-dependent lLTM; acquisition, MTM, and eLTM are still impaired. Thus, during conditioning, the cAMP-PKA cascade mediates the induction of the transcription-dependent lLTM, depending on the satiation level. This result provides the first evidence for a central and distinct function of the cAMP-PKA cascade connecting satiation level with learning.

Impairment of Coronary Arteriolar Endothelium-Dependent Dilation after Multi-Walled Carbon Nanotube Inhalation: A Time-Course Study

PubMed Central

Stapleton, Phoebe A.; Minarchick, Valerie C.; Cumpston, Amy M.; McKinney, Walter; Chen, Bean T.; Sager, Tina M.; Frazer, David G.; Mercer, Robert R.; Scabilloni, James; Andrew, Michael E.; Castranova, Vincent; Nurkiewicz, Timothy R.

2012-01-01

Engineered nanomaterials have been developed for widespread applications due to many highly unique and desirable characteristics. The purpose of this study was to assess pulmonary inflammation and subepicardial arteriolar reactivity in response to multi-walled carbon nanotube (MWCNT) inhalation and evaluate the time course of vascular alterations. Rats were exposed to MWCNT aerosols producing pulmonary deposition. Pulmonary inflammation via bronchoalveolar lavage and MWCNT translocation from the lungs to systemic organs was evident 24 h post-inhalation. Coronary arterioles were evaluated 24–168 h post-exposure to determine microvascular response to changes in transmural pressure, endothelium-dependent and -independent reactivity. Myogenic responsiveness, vascular smooth muscle reactivity to nitric oxide, and α-adrenergic responses all remained intact. However, a severe impact on endothelium-dependent dilation was observed within 24 h after MWCNT inhalation, a condition which improved, but did not fully return to control after 168 h. In conclusion, results indicate that MWCNT inhalation not only leads to pulmonary inflammation and cytotoxicity at low lung burdens, but also a low level of particle translocation to systemic organs. MWCNT inhalation also leads to impairments of endothelium-dependent dilation in the coronary microcirculation within 24 h, a condition which does not fully dissipate within 168 h. The innovations within the field of nanotechnology, while exciting and novel, can only reach their full potential if toxicity is first properly assessed. PMID:23203034

A locally initiated and executed measles outbreak response immunization campaign in the nylon health district, Douala Cameroon 2011

PubMed Central

2013-01-01

The Cameroon health system is divided into central, intermediate and peripheral levels. Of the 43 health districts with a measles outbreak in Cameroon in 2011, only the Nylon Health District organized a documented outbreak response immunization. We present the methods and results of the response campaign solely shouldered by the district and intermediate level. The risk group, targets and neighborhoods to be vaccinated were identified after a detailed analysis of initial cases. The intermediate level defined strategies, provided logistics, capacity building and 41% of the operational budget while 59% was completed by the peripheral level. Microsoft Office Excel 2007 was used to estimate coverage rates and to draw an epidemic curve. The response immunization campaign was organized on the 14th epidemiological week, 10 weeks after the onset of the outbreak which ended 11 weeks thereafter. A total of 15867(108.5%) children aged 9-59 months were vaccinated in five health areas at a direct cost (vaccines excluded) of 71.34FCFA ($0.143) per vaccinated child. An additional 824 children aged 9-59 months were vaccinated around the residence of notified cases in neighborhoods which were not involved in the response campaign. The number of cases after the response campaign was lower than before. Once vaccines are available, prompt outbreak response campaigns can be organized at operational level to obtain commendable results instead of depending solely on international organizations or central levels. Decision makers at the intermediate and operational levels should redeploy available funds during emergencies to prevent the development of extreme public health conditions. PMID:23497712

Dose-dependent immunogenicity of a soluble Neospora caninum tachyzoite-extract vaccine formulated with a soy lecithin/β-glucan adjuvant in cattle.

PubMed

Mansilla, F C; Czepluch, W; Malacari, D A; Hecker, Y P; Bucafusco, D; Franco-Mahecha, O L; Moore, D P; Capozzo, A V

2013-10-18

Mice immunized with a soluble extract of Neospora caninum tachyzoites (sNcAg) formulated with Providean-AVEC, an aqueous soy-based adjuvant, are fully protected from N. caninum multiplication. Here we evaluated the dose-dependent immunogenicity of this vaccine formulation in cattle. Cattle (N=3 per group) were immunized with two applications (30 days apart) of formulations containing Providean-AVEC and different payloads of sNcAg (100, 50 and 10 μg), that were five to fifty times lower than the only reported study using this same antigen in cattle. Kinetics and magnitude of the vaccine-induced immune responses were dose-dependent. Cattle immunized with 100 μg-sNcAg elicited high-avidity specific antibodies 3 weeks after the primary vaccination while those that received 50 μg of antigen had maximum levels of specific high-avidity antibodies 5 days after the day 30 boost. Vaccination with 10 μg of sNcAg induced comparable antibody responses after 2 weeks post re-vaccination. IgG1 was the predominant isotype in all vaccinated animals. Maximum systemic IFN-γ levels were measured in cattle immunized with 50 and 100 μg-sNcAg (14 ± 2.8 ng/ml). CD4(+)-T cells from vaccinated animals proliferated after sNcAg stimulation in vitro, producing IFN-γ. Recall IFN-γ responses mediated by CD4(+)-T cells were detected up to 140 days post vaccination. Formulations containing Providean-AVEC and 50 μg of sNcAg stimulated broad cellular and humoral immune responses against N. caninum in cattle. The profile and magnitude of the immune response elicited by this vaccine can be modified by the antigen-dose and vaccination schedule. This is the first dose-response study performed in cattle using sNcAg as antigen. Copyright © 2013 Elsevier B.V. All rights reserved.

Interclonal proteomic responses to predator exposure in Daphnia magna may depend on predator composition of habitats.

PubMed

Otte, Kathrin A; Schrank, Isabella; Fröhlich, Thomas; Arnold, Georg J; Laforsch, Christian

2015-08-01

Phenotypic plasticity, the ability of one genotype to express different phenotypes in response to changing environmental conditions, is one of the most common phenomena characterizing the living world and is not only relevant for the ecology but also for the evolution of species. Daphnia, the water flea, is a textbook example for predator-induced phenotypic plastic defences; however, the analysis of molecular mechanisms underlying these inducible defences is still in its early stages. We exposed Daphnia magna to chemical cues of the predator Triops cancriformis to identify key processes underlying plastic defensive trait formation. To get a more comprehensive idea of this phenomenon, we studied four genotypes with five biological replicates each, originating from habitats characterized by different predator composition, ranging from predator-free habitats to habitats containing T. cancriformis. We analysed the morphologies as well as proteomes of predator-exposed and control animals. Three genotypes showed morphological changes when the predator was present. Using a high-throughput proteomics approach, we found 294 proteins which were significantly altered in their abundance after predator exposure in a general or genotype-dependent manner. Proteins connected to genotype-dependent responses were related to the cuticle, protein synthesis and calcium binding, whereas the yolk protein vitellogenin increased in abundance in all genotypes, indicating their involvement in a more general response. Furthermore, genotype-dependent responses at the proteome level were most distinct for the only genotype that shares its habitat with Triops. Altogether, our study provides new insights concerning genotype-dependent and general molecular processes involved in predator-induced phenotypic plasticity in D. magna. © 2015 John Wiley & Sons Ltd.

Impacts and responses to environmental change in coastal livelihoods of south-west Bangladesh.

PubMed

Hossain, Mostafa A R; Ahmed, Munir; Ojea, Elena; Fernandes, Jose A

2018-05-12

Aquatic ecosystems are of global importance for maintaining high levels of biodiversity and ecosystem services, and for the number of livelihoods dependent on them. In Bangladesh, coastal and delta communities rely on these systems for a livelihood, and the sustainability of the productivity is seriously threatened by both climate change and unsustainable management. These multiple drivers of change shape the livelihood dependence and adaptation responses, where a better understanding is needed to achieve sustainable management in these systems, while maintaining and improving dependent livelihoods. This need has been addressed in this study in the region of Satkhira, in the southwest coast of Bangladesh, where livelihoods are highly dependent on aquatic systems for food supply and income. Traditional wild fish harvest in the rivers and aquaculture systems, including ghers, ponds, and crab points have been changing in terms of the uses and intensity of management, and suffering from climate change impacts as well. By means of six focus groups with 50 participants total, and validated by expert consultations, we conduct an analysis to understand the main perceived impacts from climate and human activities; and the adaptation responses from the aquatic system livelihoods. We find that biodiversity has decreased drastically, while farmed species have increased and shrimp gher farming turned more intensive becoming the main source of income. All these changes have important implications for food supply in the region and environmental sustainability. Dramatic responses taken in the communities include exit the fisheries and migration, and more adaptive responses include species diversification, crab fattening and working more on the pond and gher infrastructure. This study evidences the results of the combination of multiple stressors in productive systems and the barriers to adaptation in aquatic ecosystem dependent communities. Copyright © 2017 Elsevier B.V. All rights reserved.

Reward-related brain response and craving correlates of marijuana cue exposure: a preliminary study in treatment-seeking marijuana-dependent subjects.

PubMed

Goldman, Marina; Szucs-Reed, Regina P; Jagannathan, Kanchana; Ehrman, Ronald N; Wang, Ze; Li, Yin; Suh, Jesse J; Kampman, Kyle; O'Brien, Charles P; Childress, Anna Rose; Franklin, Teresa R

2013-01-01

: Determining the brain substrates underlying the motivation to abuse addictive drugs is critical for understanding and treating addictive disorders. Laboratory neuroimaging studies have demonstrated differential activation of limbic and motivational circuitry (eg, amygdala, hippocampus, ventral striatum, insula, and orbitofrontal cortex) triggered by cocaine, heroin, nicotine, and alcohol cues. The literature on neural responses to marijuana cues is sparse. Thus, the goals of this study were to characterize the brain's response to marijuana cues, a major motivator underlying drug use and relapse, and determine whether these responses are linked to self-reported craving in a clinically relevant population of treatment-seeking marijuana-dependent subjects. : Marijuana craving was assessed in 12 marijuana-dependent subjects using the Marijuana Craving Questionnaire-Short Form. Subsequently, blood oxygen level dependent functional magnetic resonance imaging data were acquired during exposure to alternating 20-second blocks of marijuana-related versus matched nondrug visual cues. : Brain activation during marijuana cue exposure was significantly greater in the bilateral amygdala and the hippocampus. Significant positive correlations between craving scores and brain activation were found in the ventral striatum and the medial and lateral orbitofrontal cortex (P < 0.0001). : This study presents direct evidence for a link between reward-relevant brain responses to marijuana cues and craving and extends the current literature on marijuana cue reactivity. Furthermore, the correlative relationship between craving and brain activity in reward-related regions was observed in a clinically relevant sample (treatment-seeking marijuana-dependent subjects). Results are consistent with prior findings in cocaine, heroin, nicotine, and alcohol cue studies, indicating that the brain substrates of cue-triggered drug motivation are shared across abused substances.

Immunotoxicity and biodistribution analysis of arsenic trioxide in C57Bl/6 mice following a 2-week inhalation exposure

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

Burchiel, Scott W., E-mail: Sburchiel@salud.unm.ed; Mitchell, Leah A.; Lauer, Fredine T.

2009-12-15

In these studies the immunotoxicity of arsenic trioxide (ATO, As{sub 2}O{sub 3}) was evaluated in mice following 14 days of inhalation exposures (nose only, 3 h per day) at concentrations of 50 mug/m{sup 3} and 1 mg/m{sup 3}. A biodistribution analysis performed immediately after inhalation exposures revealed highest levels of arsenic in the kidneys, bladder, liver, and lung. Spleen cell levels were comparable to those found in the blood, with the highest concentration of arsenic detected in the spleen being 150 mug/g tissue following the 1 mg/m{sup 3} exposures. No spleen cell cytotoxicity was observed at either of the twomore » exposure levels. There were no changes in spleen cell surface marker expression for B cells, T cells, macrophages, and natural killer (NK) cells. There were also no changes detected in the B cell (LPS-stimulated) and T cell (Con A-stimulated) proliferative responses of spleen cells, and no changes were found in the NK-mediated lysis of Yac-1 target cells. The primary T-dependent antibody response was, however, found to be highly susceptible to ATO suppression. Both the 50 mug/m{sup 3} and 1 mg/m{sup 3} exposures produced greater than 70% suppression of the humoral immune response to sheep red blood cells. Thus, the primary finding of this study is that the T-dependent humoral immune response is extremely sensitive to suppression by ATO and assessment of humoral immune responses should be considered in evaluating the health effects of arsenic containing agents.« less

Bacterial and Phytoplankton Responses to Nutrient Amendments in a Boreal Lake Differ According to Season and to Taxonomic Resolution

PubMed Central

Peura, Sari; Eiler, Alexander; Hiltunen, Minna; Nykänen, Hannu; Tiirola, Marja; Jones, Roger I.

2012-01-01

Nutrient limitation and resource competition in bacterial and phytoplankton communities may appear different when considering different levels of taxonomic resolution. Nutrient amendment experiments conducted in a boreal lake on three occasions during one open water season revealed complex responses in overall bacterioplankton and phytoplankton abundance and biovolume. In general, bacteria were dominant in spring, while phytoplankton was clearly the predominant group in autumn. Seasonal differences in the community composition of bacteria and phytoplankton were mainly related to changes in observed taxa, while the differences across nutrient treatments within an experiment were due to changes in relative contributions of certain higher- and lower-level phylogenetic groups. Of the main bacterioplankton phyla, only Actinobacteria had a treatment response that was visible even at the phylum level throughout the season. With increasing resolution (from 75 to 99% sequence similarity) major responses to nutrient amendments appeared using 454 pyrosequencing data of 16S rRNA amplicons. This further revealed that OTUs (defined by 97% sequence similarity) annotated to the same highly resolved freshwater groups appeared to occur during different seasons and were showing treatment-dependent differentiation, indicating that OTUs within these groups were not ecologically coherent. Similarly, phytoplankton species from the same genera responded differently to nutrient amendments even though biovolumes of the majority of taxa increased when both nitrogen and phosphorus were added simultaneously. The bacterioplankton and phytoplankton community compositions showed concurrent trajectories that could be seen in synchronous succession patterns over the season. Overall, our data revealed that the response of both communities to nutrient changes was highly dependent on season and that contradictory results may be obtained when using different taxonomic resolutions. PMID:22715392

Enhanced decomposition offsets enhanced productivity and soil carbon accumulation in coastal wetlands responding to climate change

USGS Publications Warehouse

Kirwan, M.L.; Blum, L.K.

2011-01-01

Coastal wetlands are responsible for about half of all carbon burial in oceans, and their persistence as a valuable ecosystem depends largely on the ability to accumulate organic material at rates equivalent to relative sea level rise. Recent work suggests that elevated CO2 and temperature warming will increase organic matter productivity and the ability of marshes to survive sea level rise. However, we find that organic decomposition rates increase by about 12% per degree of warming. Our measured temperature sensitivity is similar to studies from terrestrial systems, twice as high as the response of salt marsh productivity to temperature warming, and roughly equivalent to the productivity response associated with elevated CO2 in C3 marsh plants. Therefore, enhanced CO2 and warmer temperatures may actually make marshes less resilient to sea level rise, and tend to promote a release of soil carbon. Simple projections indicate that elevated temperatures will increase rates of sea level rise more than any acceleration in organic matter accumulation, suggesting the possibility of a positive feedback between climate, sea level rise, and carbon emissions in coastal environments.

Ethylene regulates Apple (Malus x domestica) fruit softening through a dose x time-dependent mechanism and through differential sensitivities and dependencies of cell wall-modifying genes.

PubMed

Ireland, Hilary S; Gunaseelan, Kularajathevan; Muddumage, Ratnasiri; Tacken, Emma J; Putterill, Jo; Johnston, Jason W; Schaffer, Robert J

2014-05-01

In fleshy fruit species that have a strong requirement for ethylene to ripen, ethylene is synthesized autocatalytically, producing increasing concentrations as the fruits ripen. Apple fruit with the ACC OXIDASE 1 (ACO1) gene suppressed cannot produce ethylene autocatalytically at ripening. Using these apple lines, an ethylene sensitivity dependency model was previously proposed, with traits such as softening showing a high dependency for ethylene as well as low sensitivity. In this study, it is shown that the molecular control of fruit softening is a complex process, with different cell wall-related genes being independently regulated and exhibiting differential sensitivities to and dependencies on ethylene at the transcriptional level. This regulation is controlled through a dose × time mechanism, which results in a temporal transcriptional response that would allow for progressive cell wall disassembly and thus softening. This research builds on the sensitivity dependency model and shows that ethylene-dependent traits can progress over time to the same degree with lower levels of ethylene. This suggests that a developmental clock measuring cumulative ethylene controls the fruit ripening process.

Sea level driven marsh expansion in a coupled model of marsh erosion and migration

USGS Publications Warehouse

Kirwan, Matthew L.; Walters, David C.; Reay, William G.; Carr, Joel

2016-01-01

Coastal wetlands are among the most valuable ecosystems on Earth, where ecosystem services such as flood protection depend nonlinearly on wetland size and are threatened by sea level rise and coastal development. Here we propose a simple model of marsh migration into adjacent uplands and couple it with existing models of seaward edge erosion and vertical soil accretion to explore how ecosystem connectivity influences marsh size and response to sea level rise. We find that marsh loss is nearly inevitable where topographic and anthropogenic barriers limit migration. Where unconstrained by barriers, however, rates of marsh migration are much more sensitive to accelerated sea level rise than rates of edge erosion. This behavior suggests a counterintuitive, natural tendency for marsh expansion with sea level rise and emphasizes the disparity between coastal response to climate change with and without human intervention.

Autoimmunity to Tropomyosin-Specific Peptides Induced by Mycobacterium leprae in Leprosy Patients: Identification of Mimicking Proteins.

PubMed

Singh, Itu; Yadav, Asha Ram; Mohanty, Keshar Kunja; Katoch, Kiran; Sharma, Prashant; Pathak, Vinay Kumar; Bisht, Deepa; Gupta, Umesh D; Sengupta, Utpal

2018-01-01

It has been shown earlier that there is a rise in the levels of autoantibodies and T cell response to cytoskeletal proteins in leprosy. Our group recently demonstrated a rise in both T and B cell responses to keratin and myelin basic protein in all types of leprosy patients and their associations in type 1 reaction (T1R) group of leprosy. In this study, we investigated the association of levels of autoantibodies and lymphoproliferation against myosin in leprosy patients across the spectrum and tried to find out the mimicking proteins or epitopes between host protein and protein/s of Mycobacterium leprae . One hundred and sixty-nine leprosy patients and 55 healthy controls (HC) were enrolled in the present study. Levels of anti-myosin antibodies and T-cell responses against myosin were measured by ELISA and lymphoproliferation assay, respectively. Using 2-D gel electrophoresis, western blot and MALDI-TOF/TOF antibody-reactive spots were identified. Three-dimensional structure of mimicking proteins was modeled by online server. B cell epitopes of the proteins were predicted by BCPREDS server 1.0 followed by identification of mimicking epitopes. Mice of inbred BALB/c strain were hyperimmunized with M. leprae soluble antigen (MLSA) and splenocytes and lymph node cells of these animals were adoptively transferred to naïve mice. Highest level of anti-myosin antibodies was noted in sera of T1R leprosy patients. We observed significantly higher levels of lymphoproliferative response ( p  < 0.05) with myosin in all types of leprosy patients compared to HC. Further, hyperimmunization of inbred BALB/c strain of female mice and rabbit with MLSA revealed that both hyperimmunized rabbit and mice evoked heightened levels of antibodies against myosin and this autoimmune response could be adoptively transferred from hyperimmunized to naïve mice. Tropomyosin was found to be mimicking with ATP-dependent Clp protease ATP-binding subunit of M. leprae . We found four mimicking epitopes between these sequences. These data suggest that these mimicking proteins tropomyosin and ATP-dependent Clp protease ATP-binding subunit of M. leprae or more precisely mimicking epitopes (four B cell epitopes) might be responsible for extensive tissue damage during type1 reaction in leprosy.

Cyclic AMP differentiates two separate but interacting pathways of phosphoinositide hydrolysis in the DDT1-MF2 smooth muscle cell line.

PubMed

Schachter, J B; Wolfe, B B

1992-03-01

The activation of adenosine A1 receptors in DDT1-MF2 smooth muscle cells resulted in both the inhibition of agonist-stimulated cAMP accumulation and the potentiation of norepinephrine-stimulated phosphoinositide hydrolysis. Pharmacological analysis indicated the involvement of an A1 adenosine receptor subtype in both of these responses. In the absence of norepinephrine, the activation of the adenosine receptor did not directly stimulate phosphoinositide hydrolysis. The adenosine receptor-mediated augmentation of norepinephrine-stimulated phosphoinositide hydrolysis was pertussis toxin sensitive and was selectively antagonized by agents that mimicked cAMP (8-bromo-cAMP) or raised cellular cAMP levels (forskolin). This initially suggested that cAMP might partially regulate the magnitude of the phospholipase C response to norepinephrine and that adenosine agonists might enhance the phospholipase C response by reducing cAMP levels. However, neither the reduction of cellular cAMP levels by other agents nor the inhibition of cAMP-dependent protein kinase was sufficient to replicate the action of adenosine receptor activation on phosphoinositide hydrolysis. Thus, in the presence of norepinephrine, adenosine receptor agonists appear to stimulate phosphoinositide hydrolysis via a pathway that is separate from, but dependent upon, that of norepinephrine. This second pathway can be distinguished from that which is stimulated by norepinephrine on the basis of its sensitivity to inhibition by both cAMP and pertussis toxin.

Atg7- and Keap1-dependent autophagy protects breast cancer cell lines against mitoquinone-induced oxidative stress

PubMed Central

Gonzalez, Yanira; Aryal, Baikuntha; Chehab, Leena; Rao, V. Ashutosh

2014-01-01

The interplay between oxidative stress and autophagy is critical for determining the fate of cancer cells exposed to redox-active and cytotoxic chemotherapeutic agents. Mitoquinone (MitoQ), a mitochondrially-targeted redox-active ubiquinone conjugate, selectively kills breast cancer cells over healthy mammary epithelial cells. We reported previously that MitoQ, although a derivative of the antioxidant ubiquinone, can generate excess ROS and trigger the Keap1-Nrf2 antioxidant response in the MDA-MB-231 cell line. Following MitoQ treatment, a greater number of cells underwent autophagy than apoptosis. However, the relationship between MitoQ-induced oxidative stress and autophagy as a primary cellular response was unclear. In this report, we demonstrate that MitoQ induces autophagy related gene 7 (Atg7)-dependent, yet Beclin-1-independent, autophagy marked by an increase in LC3-II. Both the ATG7-deficient human MDA-MB-231 cells and Atg7-knockout mouse embryonic fibroblasts exhibited lower levels of autophagy following MitoQ treatment than their respective wild-type counterparts. Increased apoptosis was confirmed in these autophagy-deficient isogenic cell line pairs, indicating that autophagy was attempted for survival in wild type cell lines. Furthermore, we observed higher levels of ROS in Atg7-deficient cells, as measured by hydroethidine oxidation. In Atg7-deficient cells, redox-sensitive Keap1 degradation was decreased, suggesting autophagy- and Atg7-dependent degradation of Keap1. Conversely, downregulation of Keap1 decreased autophagy levels, increased Nrf2 activation, upregulated cytoprotective antioxidant gene expression, and caused accumulation of p62, suggesting a feedback loop between ROS-regulated Keap1-Nrf2 and Atg7-regulated autophagy. Our data indicate that excessive ROS causes the upregulation of autophagy, and autophagy acts as an antioxidant feedback response triggered by cytotoxic levels of MitoQ. PMID:24681637

Atg7- and Keap1-dependent autophagy protects breast cancer cell lines against mitoquinone-induced oxidative stress.

PubMed

Gonzalez, Yanira; Aryal, Baikuntha; Chehab, Leena; Rao, V Ashutosh

2014-03-30

The interplay between oxidative stress and autophagy is critical for determining the fate of cancer cells exposed to redox-active and cytotoxic chemotherapeutic agents. Mitoquinone (MitoQ), a mitochondrially-targeted redox-active ubiquinone conjugate, selectively kills breast cancer cells over healthy mammary epithelial cells. We reported previously that MitoQ, although a derivative of the antioxidant ubiquinone, can generate excess ROS and trigger the Keap1-Nrf2 antioxidant response in the MDA-MB-231 cell line. Following MitoQ treatment, a greater number of cells underwent autophagy than apoptosis. However, the relationship between MitoQ-induced oxidative stress and autophagy as a primary cellular response was unclear. In this report, we demonstrate that MitoQ induces autophagy related gene 7 (Atg7)-dependent, yet Beclin-1-independent, autophagy marked by an increase in LC3-II. Both the ATG7-deficient human MDA-MB-231 cells and Atg7-knockout mouse embryonic fibroblasts exhibited lower levels of autophagy following MitoQ treatment than their respective wild-type counterparts. Increased apoptosis was confirmed in these autophagy-deficient isogenic cell line pairs, indicating that autophagy was attempted for survival in wild type cell lines. Furthermore, we observed higher levels of ROS in Atg7-deficient cells, as measured by hydroethidine oxidation. In Atg7-deficient cells, redox-sensitive Keap1 degradation was decreased, suggesting autophagy- and Atg7-dependent degradation of Keap1. Conversely, downregulation of Keap1 decreased autophagy levels, increased Nrf2 activation, upregulated cytoprotective antioxidant gene expression, and caused accumulation of p62, suggesting a feedback loop between ROS-regulated Keap1-Nrf2 and Atg7-regulated autophagy. Our data indicate that excessive ROS causes the upregulation of autophagy, and autophagy acts as an antioxidant feedback response triggered by cytotoxic levels of MitoQ.

Injury Prevention in Aircraft Crashes: Investigative Techniques and Applications (la Prevention des lesions lors des accidents d’ avions: les techniques d’investigation et leurs applications)

DTIC Science & Technology

1998-02-01

provide the aircrew and passengers with a level of protection commensurate with the risk of operating aircraft in the military and civilian...the time taken to reach peak acceleration and upon the peak acceleration level attained. Long duration acceleration, which can be experienced in...acceleration depends principally on the plateau level of the acceleration imposed on the body, as the response to long duration acceleration is due

Neuron-derived orphan receptor 1 transduces survival signals in neuronal cells in response to hypoxia-induced apoptotic insults.

PubMed

Chio, Chung-Ching; Wei, Li; Chen, Tyng Guey; Lin, Chien-Min; Shieh, Ja-Ping; Yeh, Poh-Shiow; Chen, Ruei-Ming

2016-06-01

OBJECT Hypoxia can induce cell death or trigger adaptive mechanisms to guarantee cell survival. Neuron-derived orphan receptor 1 (NOR-1) works as an early-response protein in response to a variety of environmental stresses. In this study, the authors evaluated the roles of NOR-1 in hypoxia-induced neuronal insults. METHODS Neuro-2a cells were exposed to oxygen/glucose deprivation (OGD). Cell viability, cell morphology, cas-pase-3 activity, DNA fragmentation, and cell apoptosis were assayed to determine the mechanisms of OGD-induced neuronal insults. RNA and protein analyses were carried out to evaluate the effects of OGD on expressions of NOR-1, cAMP response element-binding (CREB), and cellular inhibitor of apoptosis protein 2 (cIAP2) genes. Translations of these gene expressions were knocked down using RNA interference. Mice subjected to traumatic brain injury (TBI) and NOR-1 was immunodetected. RESULTS Exposure of neuro-2a cells to OGD decreased cell viability in a time-dependent manner. Additionally, OGD led to cell shrinkage, DNA fragmentation, and cell apoptosis. In parallel, treatment of neuro-2a cells with OGD time dependently increased cellular NOR-1 mRNA and protein expressions. Interestingly, administration of TBI also augmented NOR-1 levels in the impacted regions of mice. As to the mechanism, exposure to OGD increased nuclear levels of the transcription factor CREB protein. Downregulating CREB expression using RNA interference simultaneously inhibited OGD-induced NOR-1 mRNA expression. Also, levels of cIAP2 mRNA and protein in neuro-2a cells were augmented by OGD. After reducing cIAP2 translation, OGD-induced cell death was reduced. Sequentially, application of NOR-1 small interfering RNA to neuro-2a cells significantly inhibited OGD-induced cIAP2 mRNA expression and concurrently alleviated hypoxia-induced alterations in cell viability, caspase-3 activation, DNA damage, and cell apoptosis. CONCLUSIONS This study shows that NOR-1 can transduce survival signals in neuronal cells responsible for hypoxiainduced apoptotic insults through activation of a CREB/cIAP2-dependent mechanism.

An item response theory analysis of DSM-IV criteria for hallucinogen abuse and dependence in adolescents

PubMed Central

Wu, Li-Tzy; Pan, Jeng-Jong; Yang, Chongming; Reeve, Bryce B.; Blazer, Dan G.

2009-01-01

Aim This study applied both item response theory (IRT) and multiple indicators–multiple causes (MIMIC) methods to evaluate item-level psychometric properties of diagnostic questions for hallucinogen use disorders (HUDs), differential item functioning (DIF), and predictors of latent HUD. Methods Data were drawn from 2004–2006 National Surveys on Drug Use and Health. Analyses were based on 1548 past-year hallucinogen users aged 12–17 years. Substance use and symptoms were assessed by audio computer-assisted self-interviewing methods. Results Abuse and dependence criteria empirically were arrayed along a single continuum of severity. All abuse criteria indicated middle-to-high severity on the IRT-defined HUD continuum, while dependence criteria captured a wider range from the lowest (tolerance and time spent) to the highest (taking larger amounts and inability to cut down) severity levels. There was indication of DIF by hallucinogen users’ age, gender, race/ethnicity, and ecstasy use status. Adjusting for DIF, ecstasy users (vs. non-ecstasy hallucinogen users), females (vs. males), and whites (vs. Hispanics) exhibited increased odds of HUD. Conclusions Symptoms of hallucinogen abuse and dependence empirically do not reflect two discrete conditions in adolescents. Trends and problems related to hallucinogen use among girls and whites should be examined further to inform the designs of effective gender-appropriate and culturally sensitive prevention programs. PMID:19896773

Triclosan exposure modulates estrogen-dependent responses in the rat uterotrophic assay.

EPA Science Inventory

Our previous studies in the juvenile rat indicated that the biocide triclosan may alter steroid hormone levels. Here, we hypothesize that triclosan possesses estrogenic activity. In the first study, we evaluated the potential estrogenicity of triclosan using the immature rat uter...

Examining Effects of Technology Level and Reinforcer Arrangements on Preference and Efficacy

ERIC Educational Resources Information Center

Hoffmann, Audrey N.

2017-01-01

Understanding dimensions that influence reinforcement is important for applied behavior analysts. Preference, and reinforcer effectiveness, may change depending upon several dimensions of reinforcement. Two influential dimensions that may influence preference and reinforcer efficacy are response-reinforcer arrangements and stimulus type. Many…

Sex-dependent effects of restraint on nociception and pituitary-adrenal hormones in the rat.

PubMed

Aloisi, A M; Steenbergen, H L; van de Poll, N E; Farabollini, F

1994-05-01

The sex-dependent effects of acute restraint (RT) on nociceptive and pituitary-adrenal responses were investigated in the rat. In a first experiment, the effect of 30 min RT on pain sensitivity was evaluated through repeated use of the tail withdrawal test during and after treatment. RT induced an increase in the nociceptive threshold, i.e., analgesia, in males and females, but the duration and time-course of this effect varied between sexes. The latencies returned to approximately control values in females in the second half of RT, but in males they remained higher for the whole period of RT and immediately afterwards. Twenty-four hours later, males displayed longer latencies than controls in response to simple reexposure to the environment. In a second experiment, ACTH and corticosterone plasma levels were measured immediately after 15 or 30 min of RT. ACTH and corticosterone were higher in restrained animals than in controls after both periods of treatment, and in both sexes; however, females showed higher basal and stress corticosterone levels than males. The role played by corticosteroids in the nociceptive responses of the two sexes is discussed.

Ott1 (Rbm15) regulates thrombopoietin response in hematopoietic stem cells through alternative splicing of c-Mpl.

PubMed

Xiao, Nan; Laha, Suparna; Das, Shankar P; Morlock, Kayla; Jesneck, Jonathan L; Raffel, Glen D

2015-02-05

Thrombopoietin (Thpo) signaling through the c-Mpl receptor promotes either quiescence or proliferation of hematopoietic stem cells (HSCs) in a concentration-dependent manner; however, in vivo Thpo serum levels are responsive to platelet mass rather than HSC demands, suggesting additional regulation exists. Ott1 (Rbm15), a spliceosomal component originally identified as a fusion partner in t(1;22)-associated acute megakaryocytic leukemia, is also essential for maintaining HSC quiescence under stress. Ott1 controls the alternative splicing of a dominant negative isoform, Mpl-TR, capable of inhibiting HSC engraftment and attenuating Thpo signaling. Ott1, which associates with Hdac3 and the histone methyltransferase, Setd1b, binds to both c-Mpl RNA and chromatin and regulates H4 acetylation and H3K4me3 marks. Histone deacetylase or histone methyltransferase inhibition also increases Mpl-TR levels, suggesting that Ott1 uses an underlying epigenetic mechanism to control alternative splicing of c-Mpl. Manipulation of Ott1-dependent alternative splicing may therefore provide a novel pharmacologic avenue for regulating HSC quiescence and proliferation in response to Thpo. © 2015 by The American Society of Hematology.

In C. elegans, high levels of dsRNA allow RNAi in the absence of RDE-4.

PubMed

Habig, Jeffrey W; Aruscavage, P Joseph; Bass, Brenda L

2008-01-01

C. elegans Dicer requires an accessory double-stranded RNA binding protein, RDE-4, to enact the first step of RNA interference, the cleavage of dsRNA to produce siRNA. While RDE-4 is typically essential for RNAi, we report that in the presence of high concentrations of trigger dsRNA, rde-4 deficient animals are capable of silencing a transgene. By multiple criteria the silencing occurs by the canonical RNAi pathway. For example, silencing is RDE-1 dependent and exhibits a decrease in the targeted mRNA in response to an increase in siRNA. We also find that high concentrations of dsRNA trigger lead to increased accumulation of primary siRNAs, consistent with the existence of a rate-limiting step during the conversion of primary to secondary siRNAs. Our studies also revealed that transgene silencing occurs at low levels in the soma, even in the presence of ADARs, and that at least some siRNAs accumulate in a temperature-dependent manner. We conclude that an RNAi response varies with different conditions, and this may allow an organism to tailor a response to specific environmental signals.

In C. elegans, High Levels of dsRNA Allow RNAi in the Absence of RDE-4

PubMed Central

Habig, Jeffrey W.; Aruscavage, P. Joseph; Bass, Brenda L.

2008-01-01

C. elegans Dicer requires an accessory double-stranded RNA binding protein, RDE-4, to enact the first step of RNA interference, the cleavage of dsRNA to produce siRNA. While RDE-4 is typically essential for RNAi, we report that in the presence of high concentrations of trigger dsRNA, rde-4 deficient animals are capable of silencing a transgene. By multiple criteria the silencing occurs by the canonical RNAi pathway. For example, silencing is RDE-1 dependent and exhibits a decrease in the targeted mRNA in response to an increase in siRNA. We also find that high concentrations of dsRNA trigger lead to increased accumulation of primary siRNAs, consistent with the existence of a rate-limiting step during the conversion of primary to secondary siRNAs. Our studies also revealed that transgene silencing occurs at low levels in the soma, even in the presence of ADARs, and that at least some siRNAs accumulate in a temperature-dependent manner. We conclude that an RNAi response varies with different conditions, and this may allow an organism to tailor a response to specific environmental signals. PMID:19112503

Luminescence properties and scintillation response in Ce3+-doped Y2Gd1Al5-xGaxO12 (x = 2, 3, 4) single crystals

NASA Astrophysics Data System (ADS)

Chewpraditkul, Warut; Pánek, Dalibor; Brůža, Petr; Chewpraditkul, Weerapong; Wanarak, Chalerm; Pattanaboonmee, Nakarin; Babin, Vladimir; Bartosiewicz, Karol; Kamada, Kei; Yoshikawa, Akira; Nikl, Martin

2014-08-01

The compositional dependence of luminescence properties and scintillation response were investigated in Ce3+-doped Y2Gd1Al5-xGaxO12 (x = 2, 3, 4) single crystals. The Gd3+ → Ce3+ energy transfer was evidenced by photoluminescence excitation spectra of Ce3+ emission. With increasing Ga content in the garnet host, the Ce3+ luminescence from the lowest 5d level (5d1) is shifted toward higher energy due to the decrease in the crystal field splitting of the 5d levels. Light yield (LY) and its dependence on the amplifier shaping time were measured under excitation with γ-rays. High LY value of ˜38 000 ph/MeV was obtained for a Y2Gd1Al3Ga2O12:Ce sample. Scintillation decay was measured with an extended dynamical and temporal scale under the nanosecond pulse soft X-ray excitation. The decrease of both LY value and relative contribution of slower decay component in the scintillation response was observed with increasing Ga content in the garnet host.

The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults

PubMed Central

Cortese, Bernadette M.; Uhde, Thomas W.; Brady, Kathleen T.; McClernon, F. Joseph; Yang, Qing X.; Collins, Heather R.; LeMatty, Todd; Hartwell, Karen J.

2015-01-01

Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor + picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multi-sensory, but not unisensory cues, was significantly related to participants’ level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving. PMID:26475784

The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults.

PubMed

Cortese, Bernadette M; Uhde, Thomas W; Brady, Kathleen T; McClernon, F Joseph; Yang, Qing X; Collins, Heather R; LeMatty, Todd; Hartwell, Karen J

2015-12-30

Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor+picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multisensory, but not unisensory cues, was significantly related to participants' level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Light-regulated leaf expansion in two Populus species: dependence on developmentally controlled ion transport.

PubMed

Stiles, Kari A; Van Volkenburgh, Elizabeth

2002-07-01

Leaf growth responses to light have been compared in two species of Populus, P. deltoides and P. trichocarpa. These species differ markedly in morphology, anatomy, and dependence on light during leaf expansion. Light stimulates the growth rate and acidification of cell walls in P. trichocarpa but not in P. deltoides, whereas leaves of P. deltoides maintain growth in the dark. Light-induced growth is promoted in P. deltoides when cells are provided 50-100 mM KCl. In both species, light initially depolarizes, then hyperpolarizes mesophyll plasma membranes. However, in the dark, the resting E(m) of mesophyll cells in P. deltoides, but not in P. trichocarpa, is relatively insensitive to decade changes in external [K+]. Results suggest that light-stimulated leaf growth depends on developmentally regulated cellular mechanisms controlling ion fluxes across the plasma membrane. These developmental differences underlie species-level differences in growth and physiological responses to the photoenvironment.

Open-ended recursive calculation of single residues of response functions for perturbation-dependent basis sets.

PubMed

Friese, Daniel H; Ringholm, Magnus; Gao, Bin; Ruud, Kenneth

2015-10-13

We present theory, implementation, and applications of a recursive scheme for the calculation of single residues of response functions that can treat perturbations that affect the basis set. This scheme enables the calculation of nonlinear light absorption properties to arbitrary order for other perturbations than an electric field. We apply this scheme for the first treatment of two-photon circular dichroism (TPCD) using London orbitals at the Hartree-Fock level of theory. In general, TPCD calculations suffer from the problem of origin dependence, which has so far been solved by using the velocity gauge for the electric dipole operator. This work now enables comparison of results from London orbital and velocity gauge based TPCD calculations. We find that the results from the two approaches both exhibit strong basis set dependence but that they are very similar with respect to their basis set convergence.

Spatiotemporal characteristics and vascular sources of neural-specific and -nonspecific fMRI signals at submillimeter columnar resolution

PubMed Central

Moon, Chan Hong; Fukuda, Mitsuhiro; Kim, Seong-Gi

2012-01-01

The neural specificity of hemodynamic-based functional magnetic resonance imaging (fMRI) signals are dependent on both the vascular regulation and the sensitivity of the applied fMRI technique to different types and sizes of blood vessels. In order to examine the specificity of MRI-detectable hemodynamic responses, submillimeter blood oxygenation-level dependent (BOLD) and cerebral blood volume (CBV) fMRI studies were performed in a well-established cat orientation column model at 9.4 Tesla. Neural-nonspecific and -specific signals were separated by comparing the fMRI responses of orthogonal orientation stimuli. The BOLD response was dominantly neural-nonspecific, mostly originating from pial and intracortical emerging veins, and thus was highly correlated with baseline blood volume. Uneven baseline CBV may displace or distort small functional domains in high-resolution BOLD maps. The CBV response in the parenchyma exhibited dual spatiotemporal characteristics, a fast and early neural-nonspecific response (with 4.3-s time constant) and a slightly slower and delayed neural-specific response (with 9.4-s time constant). The nonspecific CBV signal originates from early-responding arteries and arterioles, while the specific CBV response, which is not correlated with baseline blood volume, arises from late-responding microvessels including small pre-capillary arterioles and capillaries. Our data indicate that although the neural specificity of CBV fMRI signals is dependent on stimulation duration, high-resolution functional maps can be obtained from steady-state CBV studies. PMID:22960251

Mapping glucose-mediated gut-to-brain signalling pathways in humans☆

PubMed Central

Little, Tanya J.; McKie, Shane; Jones, Richard B.; D'Amato, Massimo; Smith, Craig; Kiss, Orsolya; Thompson, David G.; McLaughlin, John T.

2014-01-01

Objectives Previous fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. Experimental design Changes in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250 ml) of: 1 M glucose + predosing with dexloxiglumide (CCK1 receptor antagonist), 1 M glucose + placebo, or 0.9% saline (control) + placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. Principal observations Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose + dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. Conclusions Glucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway. PMID:24685436

Emotional maltreatment is associated with atypical responding to stimulation of endogenous oxytocin release through mechanically-delivered massage in males.

PubMed

Riem, Madelon M E; De Carli, Pietro; van IJzendoorn, Marinus H; Linting, Marielle; Grewen, Karen M; Bakermans-Kranenburg, Marian J

2017-11-01

The neuropeptide oxytocin plays an important role in social behavior, parenting, and affectionate touch and there is some evidence that oxytocin release can be stimulated by massage or affectionate touch. We examined the effects of massage applied by a massage seat cover on salivary oxytocin levels in two exploratory studies using within-subject designs. In Study 1 massage effects on oxytocin levels were examined in a sample of N=20 healthy female participants. Effects of a 15-min massage session were compared to a control condition during which participants sat on a comfortable chair without a massage seat cover. Salivary oxytocin levels were measured at baseline and up to three hours after the session. We found that massage attenuated oxytocin decreases over time, indicating that massage stimulates oxytocin release. In Study 2, we examined whether effects of massage in N=46 healthy male participants depend on experiences of emotional maltreatment. In addition, we examined whether enhanced oxytocin levels after massage affect the use of excessive handgrip force in response to infant crying and laughter as measured with a handgrip dynamometer. Our findings show that massage results in elevated oxytocin levels compared to a control condition, but that the effects of massage are dependent on experiences of emotional maltreatment. Men with experiences of emotional maltreatment showed lower oxytocin levels, which did not increase after massage. Furthermore, we found that high oxytocin levels after massage were related to reduced handgrip force during exposure to infant crying and laughter, indicating that massage stimulates a sensitive response to infant signals by stimulating oxytocin release. Although massage did not affect oxytocin levels in individuals with experiences of maltreatment, it reduced the use of handgrip force in response to infant crying and laughter in these individuals. Our findings indicate that emotional maltreatment is associated with atypical responding to stimulation of endogenous oxytocin release. Copyright © 2017 Elsevier Ltd. All rights reserved.

Roles for ROS and hydrogen sulfide in the longevity response to germline loss in Caenorhabditis elegans.

PubMed

Wei, Yuehua; Kenyon, Cynthia

2016-05-17

In Caenorhabditis elegans, removing germ cells slows aging and extends life. Here we show that transcription factors that extend life and confer protection to age-related protein-aggregation toxicity are activated early in adulthood in response to a burst of reactive oxygen species (ROS) and a shift in sulfur metabolism. Germline loss triggers H2S production, mitochondrial biogenesis, and a dynamic pattern of ROS in specific somatic tissues. A cytoskeletal protein, KRI-1, plays a key role in the generation of H2S and ROS. These kri-1-dependent redox species, in turn, promote life extension by activating SKN-1/Nrf2 and the mitochondrial unfolded-protein response, respectively. Both H2S and, remarkably, kri-1-dependent ROS are required for the life extension produced by low levels of the superoxide-generator paraquat and by a mutation that inhibits respiration. Together our findings link reproductive signaling to mitochondria and define an inducible, kri-1-dependent redox-signaling module that can be invoked in different contexts to extend life and counteract proteotoxicity.

Selective Enhancement of Systemic Th1 Immunity in Immunologically Immature Rats with an Orally Administered Bacterial Extract

PubMed Central

Bowman, L. M.; Holt, P. G.

2001-01-01

Infant rats primed during the first week of life with soluble antigen displayed adult-equivalent levels of T-helper 2 (Th2)-dependent immunological memory development as revealed by production of secondary immunoglobulin G1 (IgG1) antibody responses to subsequent challenge, but in contrast to adults failed to prime for Th1-dependent IgG2b responses. We demonstrate that this Th2 bias in immune function can be redressed by oral administration to neonates of a bacterial extract (Broncho-Vaxom OM-85) comprising lyophilized fractions of several common respiratory tract bacterial pathogens. Animals given OM-85 displayed a selective upregulation in primary and secondary IgG2b responses, accompanied by increased gamma interferon and decreased interleukin-4 production (both antigen specific and polyclonal), and increased capacity for development of Th1-dependent delayed hypersensitivity to the challenge antigen. We hypothesize that the bacterial extract functions via enhancement of the process of postnatal maturation of Th1 function, which is normally driven by stimuli from the gastrointestinal commensal microflora. PMID:11349036

cGMP in ozone and NO dependent responses

PubMed Central

Ederli, Luisa; Meier, Stuart; Borgogni, Andrea; Reale, Lara; Ferranti, Francesco; Gehring, Chris

2008-01-01

We have recently reported that ozone (O3) can inhibit mitochondrial respiration and induce activation of the alternative oxidase (AOX) pathway and in particular AOX1a in tobacco. While O3 causes mitochondrial H2O2, early leaf nitric oxide (NO) as well as transient ethylene (ET) accumulation, the levels of jasmonic acid and 12-oxo-phytodienoic acid remained unchanged. It was shown that both, NO and ET dependent pathways can induce AOX1a transcription by O3. AOX plays a role in reducing reactive oxygen species (ROS) which in turn are linked to biotic and abiotic plant stresses, much like the second messengers guanosine 3′, 5′-cyclic monophosphate (cGMP). The goal is to unravel specific cGMP signatures and induction pathways downstream from O3 and NO, including transcription of AOX1a. Here we propose that some late (>3 h) responses to NO, e.g., the accumulation of phenylalanine lyase (PAL) transcripts, are critically cGMP dependent, while the early (<2 h) responses, including AOX1a induction are not. PMID:19704720

Activation of cGAS-dependent antiviral responses by DNA intercalating agents.

PubMed

Pépin, Geneviève; Nejad, Charlotte; Thomas, Belinda J; Ferrand, Jonathan; McArthur, Kate; Bardin, Philip G; Williams, Bryan R G; Gantier, Michael P

2017-01-09

Acridine dyes, including proflavine and acriflavine, were commonly used as antiseptics before the advent of penicillins in the mid-1940s. While their mode of action on pathogens was originally attributed to their DNA intercalating activity, work in the early 1970s suggested involvement of the host immune responses, characterized by induction of interferon (IFN)-like activities through an unknown mechanism. We demonstrate here that sub-toxic concentrations of a mixture of acriflavine and proflavine instigate a cyclic-GMP-AMP (cGAMP) synthase (cGAS)-dependent type-I IFN antiviral response. This pertains to the capacity of these compounds to induce low level DNA damage and cytoplasmic DNA leakage, resulting in cGAS-dependent cGAMP-like activity. Critically, acriflavine:proflavine pre-treatment of human primary bronchial epithelial cells significantly reduced rhinovirus infection. Collectively, our findings constitute the first evidence that non-toxic DNA binding agents have the capacity to act as indirect agonists of cGAS, to exert potent antiviral effects in mammalian cells. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

NOTE: Investigating the potential of polymer gel dosimetry for interventional radiology: first results

NASA Astrophysics Data System (ADS)

Antoniou, P. E.; Bousbouras, P.; Sandaltzopoulos, R.; Kaldoudi, E.

2008-04-01

Complex interventional radiology (IR) procedures contribute an increasing percentage of the overall medical radiation exposure of the population making accurate dosimetry a challenge. Magnetic resonance (MR) based polymer gel dosimetry has been widely employed in complex dosimetric problems in radiotherapy. The aim of this note is to investigate the feasibility of normoxic gel dosimetry in IR. Dose response, energy dependence and dose rate dependence were investigated in irradiation set-ups relevant to IR for a particular normoxic gel, based on methacrylic acid (MAA) as the monomer and including tetrakis-hydroxy-methyl-phosphonium chloride (THPC) as antioxidant. The gel presents a linear dose response beyond a 25 cGy threshold. No significant energy dependence was observed in the useful range of interventional radiology (80-110 kVp). A linear correlation between the gel response and dose rate was observed in the range of dose rates relevant to IR (5-8 cGy min-1). These results demonstrate a reduction of gel sensitivity at very low dose rate levels. A possible explanation of this effect is suggested.

Acid Ceramidase Expression Modulates the Sensitivity of A375 Melanoma Cells to Dacarbazine*

PubMed Central

Bedia, Carmen; Casas, Josefina; Andrieu-Abadie, Nathalie; Fabriàs, Gemma; Levade, Thierry

2011-01-01

Dacarbazine (DTIC) is the treatment of choice for metastatic melanoma, but its response in patients remains very poor. Ceramide has been shown to be a death effector and to play an important role in regulating cancer cell growth upon chemotherapy. Among ceramidases, the enzymes that catabolize ceramide, acid ceramidase (aCDase) has been implicated in cancer progression. Here we show that DTIC elicits a time- and dose-dependent decrease of aCDase activity and an increase of intracellular ceramide levels in human A375 melanoma cells. The loss of enzyme activity occurred as a consequence of reactive oxygen species-dependent activation of cathepsin B-mediated degradation of aCDase. These events preceded autophagic features and loss of cell viability. Down-regulation of acid but not neutral or alkaline ceramidase 2 resulted in elevated levels of ceramide and sensitization to the toxic effects of DTIC. Conversely, inducible overexpression of acid but not neutral ceramidase reduced ceramide levels and conferred resistance to DTIC. In conclusion, we report that increased levels of ceramide, due to enhanced degradation of aCDase, are in part responsible for the cell death effects of DTIC. These results suggest that down-regulation of aCDase alone or in combination with DTIC may represent a useful tool in the treatment of metastatic melanoma. PMID:21700700

Acid ceramidase expression modulates the sensitivity of A375 melanoma cells to dacarbazine.

PubMed

Bedia, Carmen; Casas, Josefina; Andrieu-Abadie, Nathalie; Fabriàs, Gemma; Levade, Thierry

2011-08-12

Dacarbazine (DTIC) is the treatment of choice for metastatic melanoma, but its response in patients remains very poor. Ceramide has been shown to be a death effector and to play an important role in regulating cancer cell growth upon chemotherapy. Among ceramidases, the enzymes that catabolize ceramide, acid ceramidase (aCDase) has been implicated in cancer progression. Here we show that DTIC elicits a time- and dose-dependent decrease of aCDase activity and an increase of intracellular ceramide levels in human A375 melanoma cells. The loss of enzyme activity occurred as a consequence of reactive oxygen species-dependent activation of cathepsin B-mediated degradation of aCDase. These events preceded autophagic features and loss of cell viability. Down-regulation of acid but not neutral or alkaline ceramidase 2 resulted in elevated levels of ceramide and sensitization to the toxic effects of DTIC. Conversely, inducible overexpression of acid but not neutral ceramidase reduced ceramide levels and conferred resistance to DTIC. In conclusion, we report that increased levels of ceramide, due to enhanced degradation of aCDase, are in part responsible for the cell death effects of DTIC. These results suggest that down-regulation of aCDase alone or in combination with DTIC may represent a useful tool in the treatment of metastatic melanoma.

The histone H3 variant H3.3 regulates gene body DNA methylation in Arabidopsis thaliana.

PubMed

Wollmann, Heike; Stroud, Hume; Yelagandula, Ramesh; Tarutani, Yoshiaki; Jiang, Danhua; Jing, Li; Jamge, Bhagyshree; Takeuchi, Hidenori; Holec, Sarah; Nie, Xin; Kakutani, Tetsuji; Jacobsen, Steven E; Berger, Frédéric

2017-05-18

Gene bodies of vertebrates and flowering plants are occupied by the histone variant H3.3 and DNA methylation. The origin and significance of these profiles remain largely unknown. DNA methylation and H3.3 enrichment profiles over gene bodies are correlated and both have a similar dependence on gene transcription levels. This suggests a mechanistic link between H3.3 and gene body methylation. We engineered an H3.3 knockdown in Arabidopsis thaliana and observed transcription reduction that predominantly affects genes responsive to environmental cues. When H3.3 levels are reduced, gene bodies show a loss of DNA methylation correlated with transcription levels. To study the origin of changes in DNA methylation profiles when H3.3 levels are reduced, we examined genome-wide distributions of several histone H3 marks, H2A.Z, and linker histone H1. We report that in the absence of H3.3, H1 distribution increases in gene bodies in a transcription-dependent manner. We propose that H3.3 prevents recruitment of H1, inhibiting H1's promotion of chromatin folding that restricts access to DNA methyltransferases responsible for gene body methylation. Thus, gene body methylation is likely shaped by H3.3 dynamics in conjunction with transcriptional activity.

LANGUAGE EXPERIENCE SHAPES PROCESSING OF PITCH RELEVANT INFORMATION IN THE HUMAN BRAINSTEM AND AUDITORY CORTEX: ELECTROPHYSIOLOGICAL EVIDENCE.

PubMed

Krishnan, Ananthanarayan; Gandour, Jackson T

2014-12-01

Pitch is a robust perceptual attribute that plays an important role in speech, language, and music. As such, it provides an analytic window to evaluate how neural activity relevant to pitch undergo transformation from early sensory to later cognitive stages of processing in a well coordinated hierarchical network that is subject to experience-dependent plasticity. We review recent evidence of language experience-dependent effects in pitch processing based on comparisons of native vs. nonnative speakers of a tonal language from electrophysiological recordings in the auditory brainstem and auditory cortex. We present evidence that shows enhanced representation of linguistically-relevant pitch dimensions or features at both the brainstem and cortical levels with a stimulus-dependent preferential activation of the right hemisphere in native speakers of a tone language. We argue that neural representation of pitch-relevant information in the brainstem and early sensory level processing in the auditory cortex is shaped by the perceptual salience of domain-specific features. While both stages of processing are shaped by language experience, neural representations are transformed and fundamentally different at each biological level of abstraction. The representation of pitch relevant information in the brainstem is more fine-grained spectrotemporally as it reflects sustained neural phase-locking to pitch relevant periodicities contained in the stimulus. In contrast, the cortical pitch relevant neural activity reflects primarily a series of transient temporal neural events synchronized to certain temporal attributes of the pitch contour. We argue that experience-dependent enhancement of pitch representation for Chinese listeners most likely reflects an interaction between higher-level cognitive processes and early sensory-level processing to improve representations of behaviorally-relevant features that contribute optimally to perception. It is our view that long-term experience shapes this adaptive process wherein the top-down connections provide selective gating of inputs to both cortical and subcortical structures to enhance neural responses to specific behaviorally-relevant attributes of the stimulus. A theoretical framework for a neural network is proposed involving coordination between local, feedforward, and feedback components that can account for experience-dependent enhancement of pitch representations at multiple levels of the auditory pathway. The ability to record brainstem and cortical pitch relevant responses concurrently may provide a new window to evaluate the online interplay between feedback, feedforward, and local intrinsic components in the hierarchical processing of pitch relevant information.

LANGUAGE EXPERIENCE SHAPES PROCESSING OF PITCH RELEVANT INFORMATION IN THE HUMAN BRAINSTEM AND AUDITORY CORTEX: ELECTROPHYSIOLOGICAL EVIDENCE

PubMed Central

Krishnan, Ananthanarayan; Gandour, Jackson T.

2015-01-01

Pitch is a robust perceptual attribute that plays an important role in speech, language, and music. As such, it provides an analytic window to evaluate how neural activity relevant to pitch undergo transformation from early sensory to later cognitive stages of processing in a well coordinated hierarchical network that is subject to experience-dependent plasticity. We review recent evidence of language experience-dependent effects in pitch processing based on comparisons of native vs. nonnative speakers of a tonal language from electrophysiological recordings in the auditory brainstem and auditory cortex. We present evidence that shows enhanced representation of linguistically-relevant pitch dimensions or features at both the brainstem and cortical levels with a stimulus-dependent preferential activation of the right hemisphere in native speakers of a tone language. We argue that neural representation of pitch-relevant information in the brainstem and early sensory level processing in the auditory cortex is shaped by the perceptual salience of domain-specific features. While both stages of processing are shaped by language experience, neural representations are transformed and fundamentally different at each biological level of abstraction. The representation of pitch relevant information in the brainstem is more fine-grained spectrotemporally as it reflects sustained neural phase-locking to pitch relevant periodicities contained in the stimulus. In contrast, the cortical pitch relevant neural activity reflects primarily a series of transient temporal neural events synchronized to certain temporal attributes of the pitch contour. We argue that experience-dependent enhancement of pitch representation for Chinese listeners most likely reflects an interaction between higher-level cognitive processes and early sensory-level processing to improve representations of behaviorally-relevant features that contribute optimally to perception. It is our view that long-term experience shapes this adaptive process wherein the top-down connections provide selective gating of inputs to both cortical and subcortical structures to enhance neural responses to specific behaviorally-relevant attributes of the stimulus. A theoretical framework for a neural network is proposed involving coordination between local, feedforward, and feedback components that can account for experience-dependent enhancement of pitch representations at multiple levels of the auditory pathway. The ability to record brainstem and cortical pitch relevant responses concurrently may provide a new window to evaluate the online interplay between feedback, feedforward, and local intrinsic components in the hierarchical processing of pitch relevant information. PMID:25838636

Repression of branched-chain amino acid synthesis in Staphylococcus aureus is mediated by isoleucine via CodY, and by a leucine-rich attenuator peptide.

PubMed

Kaiser, Julienne C; King, Alyssa N; Grigg, Jason C; Sheldon, Jessica R; Edgell, David R; Murphy, Michael E P; Brinsmade, Shaun R; Heinrichs, David E

2018-01-01

Staphylococcus aureus requires branched-chain amino acids (BCAAs; isoleucine, leucine, valine) for protein synthesis, branched-chain fatty acid synthesis, and environmental adaptation by responding to their availability via the global transcriptional regulator CodY. The importance of BCAAs for S. aureus physiology necessitates that it either synthesize them or scavenge them from the environment. Indeed S. aureus uses specialized transporters to scavenge BCAAs, however, its ability to synthesize them has remained conflicted by reports that it is auxotrophic for leucine and valine despite carrying an intact BCAA biosynthetic operon. In revisiting these findings, we have observed that S. aureus can engage in leucine and valine synthesis, but the level of BCAA synthesis is dependent on the BCAA it is deprived of, leading us to hypothesize that each BCAA differentially regulates the biosynthetic operon. Here we show that two mechanisms of transcriptional repression regulate the level of endogenous BCAA biosynthesis in response to specific BCAA availability. We identify a trans-acting mechanism involving isoleucine-dependent repression by the global transcriptional regulator CodY and a cis-acting leucine-responsive attenuator, uncovering how S. aureus regulates endogenous biosynthesis in response to exogenous BCAA availability. Moreover, given that isoleucine can dominate CodY-dependent regulation of BCAA biosynthesis, and that CodY is a global regulator of metabolism and virulence in S. aureus, we extend the importance of isoleucine availability for CodY-dependent regulation of other metabolic and virulence genes. These data resolve the previous conflicting observations regarding BCAA biosynthesis, and reveal the environmental signals that not only induce BCAA biosynthesis, but that could also have broader consequences on S. aureus environmental adaptation and virulence via CodY.

How to personalize ovarian stimulation in clinical practice.

PubMed

Sighinolfi, Giovanna; Grisendi, Valentina; La Marca, Antonio

2017-09-01

Controlled ovarian stimulation (COS) in in vitro fertilization (IVF) cycles is the starting point from which couple's prognosis depends. Individualization in follicle-stimulating hormone (FSH) starting dose and protocol used is based on ovarian response prediction, which depends on ovarian reserve. Anti-Müllerian hormone levels and the antral follicle count are considered the most accurate and reliable markers of ovarian reserve. A literature search was performed for studies that addressed the ability of ovarian reserve markers to predict poor and high ovarian response in assisted reproductive technology cycles. According to the predicted response to ovarian stimulation (poor- normal- or high- response), it is possible to counsel couples before treatment about the prognosis, and also to individualize ovarian stimulation protocols, choosing among GnRH-agonists or antagonists for endogenous FSH suppression, and the FSH starting dose in order to decrease the risk of cycle cancellation and ovarian hyperstimulation syndrome. In this review we discuss how to choose the best COS therapy, based on ovarian reserve markers, in order to enhance chances in IVF.

Fetal-sex dependent genomic responses in the circulating lymphocytes of arsenic-exposed pregnant women in New Hampshire.

PubMed

Bommarito, Paige A; Martin, Elizabeth; Smeester, Lisa; Palys, Thomas; Baker, Emily R; Karagas, Margaret R; Fry, Rebecca C

2017-10-01

Exposure to inorganic arsenic (iAs) during pregnancy is associated with adverse health outcomes present both at birth and later in life. A biological mechanism may include epigenetic and genomic alterations in fetal genes involved in immune functioning. To investigate the role of the maternal immune response to in utero iAs exposure, we conducted an analysis of the expression of immune-related genes in pregnant women from the New Hampshire Birth Cohort Study. A set of 31 genes was identified with altered expression in association with levels of urinary total arsenic, urinary iAs, urinary monomethylated arsenic and urinary dimethylated arsenic. Notably, maternal gene expression signatures differed when stratified on fetal sex, with a more robust inflammatory response observed in male pregnancies. Moreover, the differentially expressed genes were also related to birth outcomes. These findings highlight the sex-dependent nature of the maternal iAs-induced inflammatory response in relationship to fetal outcomes. Copyright © 2017. Published by Elsevier Inc.

Piracetam and fish orientation during parabolic aircraft flight

NASA Technical Reports Server (NTRS)

Hoffman, R. B.; Salinas, G. A.; Homick, J. L.

1980-01-01

Goldfish were flown in parabolic Keplerian trajectories in a KC-135 aircraft to assay both the effectiveness of piracetam as an antimotion sickness drug and the effectiveness of state-dependent training during periods of oscillating gravity levels. Single-frame analyses of infrared films were performed for two classes of responses - role rates in hypogravity or hypogravity orienting responses (LGR) and climbing responses in hypergravity or hypergravity orienting responses (HGR). In Experiment I, preflight training with the vestibular stressor facilitated suppression of LGR by the 10th parabola. An inverse correlation was found between the magnitudes of LGR and HGR. Piracetam was not effective in a state-dependent design, but the drug did significantly increase HGR when injected into trained fish shortly before flight. In Experiment II, injections of saline, piracetam, and modifiers of gamma-aminobutyric acid - aminooxyacetic acid (AOAA) and isonicotinic acid did not modify LGR. AOAA did significantly increase HGR. Thus, the preflight training has a beneficial effect in reducing disorientation in the fish in weightlessness, but the drugs employed were ineffective.

Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects

PubMed Central

Nam, H W; Karpyak, V M; Hinton, D J; Geske, J R; Ho, A M C; Prieto, M L; Biernacka, J M; Frye, M A; Weinshilboum, R M; Choi, D-S

2015-01-01

Acamprosate has been widely used since the Food and Drug Administration approved the medication for treatment of alcohol use disorders (AUDs) in 2004. Although the detailed molecular mechanism of acamprosate remains unclear, it has been largely known that acamprosate inhibits glutamate action in the brain. However, AUD is a complex and heterogeneous disorder. Thus, biomarkers are required to prescribe this medication to patients who will have the highest likelihood of responding positively. To identify pharmacometabolomic biomarkers of acamprosate response, we utilized serum samples from 120 alcohol-dependent subjects, including 71 responders (maintained continuous abstinence) and 49 non-responders (any alcohol use) during 12 weeks of acamprosate treatment. Notably, baseline serum glutamate levels were significantly higher in responders compared with non-responders. Importantly, serum glutamate levels of responders are normalized after acamprosate treatment, whereas there was no significant glutamate change in non-responders. Subsequent functional studies in animal models revealed that, in the absence of alcohol, acamprosate activates glutamine synthetase, which synthesizes glutamine from glutamate and ammonia. These results suggest that acamprosate reduces serum glutamate levels for those who have elevated baseline serum glutamate levels among responders. Taken together, our findings demonstrate that elevated baseline serum glutamate levels are a potential biomarker associated with positive acamprosate response, which is an important step towards development of a personalized approach to treatment for AUD. PMID:26285131

Demand Response Compensation Methodologies: Case Studies for Mexico

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

Gagne, Douglas A; Settle, Donald E; Aznar, Alexandra Y

This report examines various compensation methodologies for demand response programs in Mexico. This report presents three case studies, including New England, California, and Hawaii. Demand response (DR) can refer to a variety of approaches to changing the amount and timing of customers' electricity use, allowing the electricity supplier to more easily balance electricity supply and demand. The level of compensation for a DR program will depend greatly upon both the regulatory context of the electricity supplier, as well as the economic circumstances of the DR providers. For a regulated utility, a proposed compensation level may need to pass regulatory approval.more » To determine the value of DR resources, a regulatory body typically seeks to determine the costs that the utility would avoid if demand-side resources 'produce' energy.« less

Adaptation or Resistance: a classification of responses to sea-level rise

NASA Astrophysics Data System (ADS)

Cooper, J. A.

2016-02-01

Societal responses to sea level rise and associated coastal change are apparently diverse in nature and motivation. Most are commonly referred to as 'adaptation'. Based on a review of current practice, however, it is argued that many of these responses do not involve adaptation, but are rather resisting change. There are several instances where formerly adaptive initiatives involving human adaptability are being replaced by initiatives that resist change. A classification is presented that recognises a continuum of responses ranging from adaptation to resistance, depending upon the willingness to change human activities to accommodate environmental change. In many cases climate change adaptation resources are being used for projects that are purely resistant and which foreclose future adaptation options. It is argued that a more concise definition of adaptation is needed if coastal management is to move beyond the current position of holding the shoreline, other tah n in a few showcase examples.

Elevated-CO2 Response of Stomata and Its Dependence on Environmental Factors

PubMed Central

Xu, Zhenzhu; Jiang, Yanling; Jia, Bingrui; Zhou, Guangsheng

2016-01-01

Stomata control the flow of gases between plants and the atmosphere. This review is centered on stomatal responses to elevated CO2 concentration and considers other key environmental factors and underlying mechanisms at multiple levels. First, an outline of general responses in stomatal conductance under elevated CO2 is presented. Second, stomatal density response, its development, and the trade-off with leaf growth under elevated CO2 conditions are depicted. Third, the molecular mechanism regulating guard cell movement at elevated CO2 is suggested. Finally, the interactive effects of elevated CO2 with other factors critical to stomatal behavior are reviewed. It may be useful to better understand how stomata respond to elevated CO2 levels while considering other key environmental factors and mechanisms, including molecular mechanism, biochemical processes, and ecophysiological regulation. This understanding may provide profound new insights into how plants cope with climate change. PMID:27242858

CalQuo: automated, simultaneous single-cell and population-level quantification of global intracellular Ca2+ responses.

PubMed

Fritzsche, Marco; Fernandes, Ricardo A; Colin-York, Huw; Santos, Ana M; Lee, Steven F; Lagerholm, B Christoffer; Davis, Simon J; Eggeling, Christian

2015-11-13

Detecting intracellular calcium signaling with fluorescent calcium indicator dyes is often coupled with microscopy techniques to follow the activation state of non-excitable cells, including lymphocytes. However, the analysis of global intracellular calcium responses both at the single-cell level and in large ensembles simultaneously has yet to be automated. Here, we present a new software package, CalQuo (Calcium Quantification), which allows the automated analysis and simultaneous monitoring of global fluorescent calcium reporter-based signaling responses in up to 1000 single cells per experiment, at temporal resolutions of sub-seconds to seconds. CalQuo quantifies the number and fraction of responding cells, the temporal dependence of calcium signaling and provides global and individual calcium-reporter fluorescence intensity profiles. We demonstrate the utility of the new method by comparing the calcium-based signaling responses of genetically manipulated human lymphocytic cell lines.

Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

PubMed

Alimoradi, Houman; Matikonda, Siddharth S; Gamble, Allan B; Giles, Gregory I; Greish, Khaled

2016-01-01

Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic treatment and reduce associated side effects, several prodrug strategies have been introduced to achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia responsive drug delivery systems (which only depend on low oxygen levels) is currently naïve. This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems, oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery of genes to express anticancer proteins such as tumor necrosis alpha (TNF-α) and hypoxia-inducible transcription factors 1 alpha (HIF1α) responsive gene delivery systems.

Reversible and Irreversible Time-Dependent Behavior of GRCop-84

NASA Technical Reports Server (NTRS)

Lerch, Bradley A.; Arnold, Steven M.; Ellis, David L.

2017-01-01

A series of mechanical tests were conducted on a high-conductivity copper alloy, GRCop-84, in order to understand the time dependent response of this material. Tensile, creep, and stress relaxation tests were performed over a wide range of temperatures, strain rates, and stress levels to excite various amounts of time-dependent behavior. At low applied stresses the deformation behavior was found to be fully reversible. Above a certain stress, termed the viscoelastic threshold, irreversible deformation was observed. At these higher stresses the deformation was observed to be viscoplastic. Both reversible and irreversible regions contained time dependent deformation. These experimental data are documented to enable characterization of constitutive models to aid in design of high temperature components.

Acute starvation alters lipopolysaccharide-induced fever in leptin-dependent and -independent mechanisms in rats.

PubMed

Inoue, Wataru; Luheshi, Giamal N

2010-12-01

A decrease in leptin levels with the onset of starvation triggers a myriad of physiological responses including immunosuppression and hypometabolism/hypothermia, both of which can counteract the fever response to pathogens. Here we examined the role of leptin in LPS-induced fever in rats that were fasted for 48 h prior to inflammation with or without leptin replacement (12 μg/day). The preinflammation fasting alone caused a progressive hypothermia that was almost completely reversed by leptin replacement. The LPS (100 μg/kg)-induced elevation in core body temperature (T(core)) was attenuated in the fasted animals at 2-6 h after the injection, an effect that was not reversed by leptin replacement. Increasing the LPS dose to 1,000 μg/kg caused a long-lasting fever that remained unabated for up to 36 h after the injection in the fed rats. This sustained response was strongly attenuated in the fasted rats whose T(core) started to decrease by 18 h after the injection. Leptin replacement almost completely restored the prolonged fever. The attenuation of the prolonged fever in the fasted animals was accompanied by the diminution of proinflammatory PGE(2) in the cerebrospinal fluid and mRNA of proopiomelanocortin (POMC) in the hypothalamus. Leptin replacement prevented the fasting-induced reduction of POMC but not PGE(2). Moreover, the leptin-dependent fever maintenance correlated closely with hypothalamic POMC levels (r = 0.77, P < 0.001). These results suggest that reduced leptin levels during starvation attenuate the sustained fever response by lowering hypothalamic POMC tone but not PGE(2) synthesis.

Wide dynamic range forward suppression in marmoset inferior colliculus neurons is generated centrally and accounts for perceptual masking

PubMed Central

Nelson, Paul C.; Smith, Zachary M.; Young, Eric D.

2009-01-01

An organism’s ability to detect and discriminate sensory inputs depends on the recent stimulus history. For example, perceptual detection thresholds for a brief tone can be elevated by as much as 50 dB when following a masking stimulus. Previous work suggests that such forward masking is not a direct result of peripheral neural adaptation; the central pathway apparently modifies the representation in a way that further attenuates the input’s response to short probe signals. Here, we show that much of this transformation is complete by the level of the inferior colliculus (IC). Single-neuron extracellular responses were recorded in the central nucleus of the awake marmoset IC. The threshold for a 20-ms probe tone presented at best frequency was determined for various masker-probe delays, over a range of masker SPLs and frequencies. The most striking aspect of the data was the increased potency of forward maskers as their SPL was increased, despite the fact that the excitatory response to the masker was often saturating or non-monotonic over the same range of levels. This led to probe thresholds at high masker levels that were almost always higher than those observed in the auditory nerve. Probe threshold shifts were not usually caused by a persistent excitatory response to the masker; instead we propose a wide dynamic-range inhibitory mechanism locked to sound offset as an explanation for several key aspects of the data. These findings further delineate the role of subcortical auditory processing in the generation of a context-dependent representation of ongoing acoustic scenes. PMID:19244530

Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase.

PubMed

Latagliata, Roberto; Montagna, Chiara; Porrini, Raffaele; Di Veroli, Ambra; Leonetti, Sabrina Crescenzi; Niscola, Pasquale; Ciccone, Fabrizio; Spadea, Antonio; Breccia, Massimo; Maurillo, Luca; Rago, Angela; Spirito, Francesca; Cedrone, Michele; De Muro, Marianna; Montanaro, Marco; Andriani, Alessandro; Bagnato, Antonino; Montefusco, Enrico; Alimena, Giuliana

2016-06-01

At present, very few data are available on deferasirox (DFX) in the treatment of patients with Philadelphia-negative myeloproliferative neoplasms in fibrotic phase (FP-MPN) and transfusion dependence. To address this issue, a retrospective analysis of 28 patients (22 male and 6 female) with FP-MPN and iron overload secondary to transfusion dependence was performed, based on patients enrolled in the database of our regional cooperative group who received treatment with DFX. DFX was started after a median interval from diagnosis of 12.8 months (IR 7.1-43.1) with median ferritin values of 1415 ng/mL (IR 1168-1768). Extra-hematological toxicity was reported in 16 of 28 patients (57.1%), but only two patients discontinued treatment due to toxicity. Among 26 patients evaluable for response (≥6 months of treatment), after a median treatment period of 15.4 months (IR 8.1-22.3), 11 patients (42.3%) achieved a stable and consistent reduction in ferritin levels <1000 ng/mL. As for hematological improvement, 6 of 26 patients (23%) showed a persistent (>3 months) rise of Hb levels >1.5 g/dL, with disappearance of transfusion dependence in four cases. Treatment with DFX is feasible and effective in FP-MPN with iron overload. Moreover, in this setting, an erythroid response can occur in a significant proportion of patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The role of COX-2 and Nrf2/ARE in anti-inflammation and antioxidative stress: Aging and anti-aging.

PubMed

Luo, Cheng; Urgard, Egon; Vooder, Tõnu; Metspalu, Andres

2011-08-01

Oxidative stress and inflammation are constant features of many chronic diseases and complications, and have been linked to carcinogenesis. Cyclooxygenase 2 (COX-2), a rate-limiting enzyme for the synthesis of prostaglandins, plays important roles in physiology and pathology, but has been a source of controversy within the scientific and clinical community. However, recent work has shown that nuclear factor erythroid-2-related factor-2 (Nrf2) confers protection against oxidative stress. Furthermore, COX-2-dependent electrophile oxo-derivative (EFOX) molecules have been shown to act as anti-inflammatory mediators via activation of the Nrf2-dependent antioxidant response element (ARE). These studies have provided more insight into COX-2-mediated events. The function of all tissues, especially epithelial and endothelial tissues, declines with age, leading to the production of reactive oxygen species (ROS). COX-2 expression increases with aging in most tissues, due in part to ROS, chemical reactions, physical shearing, and dietary molecules. Here we discuss new findings related to COX-2 inflammatory and anti-inflammatory responses. Taken together, we hypothesize that COX-2 levels increase during the aging process because increasing levels of ROSs necessitate the involvement of COX-2-dependent EFOXs for anti-inflammation and Nrf2/ARE signaling for antioxidation. We also propose that COX-2 may act as an intrinsic biological aging clock due to its role in balancing inflammatory and anti-inflammatory responses. Copyright © 2011 Elsevier Ltd. All rights reserved.

Activation of aryl hydrocarbon receptor regulates the LPS/IFNγ-induced inflammatory response by inducing ubiquitin-proteosomal and lysosomal degradation of RelA/p65.

PubMed

Domínguez-Acosta, O; Vega, L; Estrada-Muñiz, E; Rodríguez, M S; Gonzalez, F J; Elizondo, G

2018-06-21

Several studies have identified the aryl hydrocarbon receptor (AhR) as a negative regulator of the innate and adaptive immune responses. However, the molecular mechanisms by which this transcription factor exerts such modulatory effects are not well understood. Interaction between AhR and RelA/p65 has previously been reported. RelA/p65 is the major NFκB subunit that plays a critical role in immune responses to infection. The aim of the present study was to determine whether the activation of AhR disrupted RelA/p65 signaling in mouse peritoneal macrophages by decreasing its half-life. The data demonstrate that the activation of AhR by TCDD and β-naphthoflavone (β-NF) decreased protein levels of the pro-inflammatory cytokines TFN-α, IL-6 and IL-12 after macrophage activation with LPS/IFNγ. In an AhR-dependent manner, TCDD treatment induces RelA/p65 ubiquitination and proteosomal degradation, an effect dependent on AhR transcriptional activity. Activation of AhR also induced lysosome-like membrane structure formation in mouse peritoneal macrophages and RelA/p65 lysosome-dependent degradation. In conclusion, these results demonstrate that AhR activation promotes RelA/p65 protein degradation through the ubiquitin proteasome system, as well as through the lysosomes, resulting in decreased pro-inflammatory cytokine levels in mouse peritoneal macrophages. Copyright © 2018. Published by Elsevier Inc.

Effects of two dominance manipulations on the stress response: Cognitive and embodied influences.

PubMed

Deuter, Christian Eric; Schächinger, Hartmut; Best, Daniel; Neumann, Roland

2016-09-01

In response to stress, physiological and mental resources are allocated towards those systems that are needed for rapid responding in terms of fight or flight. On the other hand, long term regenerative processes such as growth, digestion and reproduction are attenuated. Levels of the sex steroid testosterone are reduced in participants that suffer from chronic stress. However, beyond its role for reproductive functions, testosterone plays an important role in the regulation of social status and dominance, testosterone levels increase during competition or when the social status is challenged. The Trier Social Stress Test (TSST), a laboratory stressor with a substantial social-evaluative component, can provoke an increase in salivary testosterone levels. Still, so far the reported findings regarding acute stress effects on testosterone are equivocal, possibly due to moderating effects. In this study we experimentally manipulated social dominance in 56 healthy participants (28m) by two independent manipulations (body posture and cognitive role taking) and subjected them to the TSST. We analyzed salivary testosterone and cortisol levels as dependent measures for the endocrine stress response. The role taking manipulation interacted with the testosterone response: we found the strongest increase when participants had to put themselves in a dominant (vs. submissive) role. Our results suggest that transient changes in testosterone levels during stress reflect a response to status threat that is affected by social dominance. Copyright © 2016 Elsevier B.V. All rights reserved.

Defensive responses of Brandt's voles (Lasiopodomys brandtii) to stored cat feces.

PubMed

Hegab, Ibrahim M; Jin, Yajuan; Ye, Manhong; Wang, Aiqin; Yin, Baofa; Yang, Shengmei; Wei, Wanhong

2014-01-17

Predator odors are non-intrusive natural stressors of high ethological relevance. Animals are daily challenged with stressors of varying intensity and it is essential for their survival to respond to a wide range of threats. Behavioral and hormonal responses and changes in the level of medial hypothalamic c-fos mRNA were examined in Brandt's voles (Lasiopodomys brandtii) exposed to the feces of a domestic cat (Felis catus) stored for different periods. One hundred voles were tested in the defensive withdrawal apparatus. The voles showed an aversion to freshly collected cat feces, indicated by high levels of flight-related behaviors, increased freezing behavior, and more vigilant rearing compared to old feces. The serum levels of adrenocorticotropic hormone and corticosterone significantly increased when the voles were exposed to fresh cat feces. The level of c-fos mRNA in the medial hypothalamic region was highest in the individuals exposed to fresh cat feces. All of these behavioral, endocrine and c-fos-mRNA responses were lower when voles were subjected to older cat feces. We conclude that these responses depend on volatile chemical constituents of cat feces rather than their physical characteristics and that this accounts for the lower responses to feces stored for longer periods. © 2013. Published by Elsevier Inc. All rights reserved.

Task-dependent response conflict monitoring and cognitive control in anterior cingulate and dorsolateral prefrontal cortices.

PubMed

Kim, Chobok; Chung, Chongwook; Kim, Jeounghoon

2013-11-06

Previous experience affects our behavior in terms of adjustments. It has been suggested that the conflict monitor-controller system implemented in the prefrontal cortex plays a critical role in such adjustments. Previous studies suggested that there exists multiple conflict monitor-controller systems associated with the level of information (i.e., stimulus and response levels). In this study, we sought to test whether different types of conflicts occur at the same information processing level (i.e., response level) are independently processed. For this purpose, we designed a task paradigm to measure two different types of response conflicts using color-based and location-based conflict stimuli and measured the conflict adaptation effects associated with the two types of conflicts either independently (i.e., single conflict conditions) or simultaneously (i.e., a double-conflict condition). The behavioral results demonstrated that performance on current incongruent trials was faster only when the preceding trial was the same type of response conflict regardless of whether they included a single- or double-conflict. Imaging data also showed that anterior cingulate and dorsolateral prefrontal cortices operate in a task-specific manner. These findings suggest that there may be multiple monitor-controller loops for color-based and location-based conflicts even at the same response level. Importantly, our results suggest that double-conflict processing is qualitatively different from single-conflict processing although double-conflict shares the same sources of conflict with two single-conflict conditions. © 2013 Published by Elsevier B.V.

Neuroendocrine responses to fenfluramine and its relationship to personality in alcoholism.

PubMed

Weijers, H G; Wiesbeck, G A; Jakob, F; Böning, J

2001-01-01

This study investigates the relationship between personality and serotonergic reactivity in alcohol dependence. Personality characteristics were assessed according to the Temperament and Character model of Cloninger, the five-factor model of McCrae and Costa, Zuckerman's Sensation Seeking as well as Eysenck's impulsiveness/venturesomeness. Placebo-controlled prolactin response to the serotonin (5-HT) reuptake inhibitor/releaser fenfluramine served as an indicator for the reactivity of serotonergic neurotransmission. Forty abstinent alcohol-dependent men were subdivided into high and low prolactin responders according to their level of neuroendocrine response. High responders were characterized by decreased harm avoidance while their extraversion and venturesomeness scores were increased in comparison to low responders. The data demonstrates that harm avoidance on the one hand and extraversion/venturesomeness on the other are inversely correlated to serotonergic neurotransmission. These results support a specific relationship between personality traits and the serotonergic system.

Loss of the Sexually Dimorphic Neuro-Inflammatory Response in a Transgenic Mouse Model of Huntington's Disease.

PubMed

Renoir, Thibault; Pang, Terence Y; Shikano, Yoshiko; Li, Shanshan; Hannan, Anthony J

2015-01-01

We previously reported sex differences in depression-like behaviours in a mouse model of Huntington's disease (HD). We hypothesized that immune response could also be altered in HD mice in a sex-dependent manner. Here, we assessed the molecular effects of an acute challenge with lipopolysaccharides (LPS) in female versus male R6/1 transgenic HD mice. We found an enhancement of LPS-induced TNF-α gene expression in the hypothalamus of female HD mice. TNF-α serum levels following LPS administration were also higher in female HD mice compared to WT animals. In contrast, male HD mice exhibited reduced LPS-induced TNF-α gene expression compared to WT animals. Our findings suggest that immune response to LPS is altered in HD mice in a sex-dependent manner. These pro-inflammatory abnormalities may contribute to the sexually dimorphic depression-like behaviours displayed by this mouse model of HD.

Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer.

PubMed

Sturgeon, Kathleen; Digiovanni, Laura; Good, Jerene; Salvatore, Domenick; Fenderson, Desiré; Domchek, Susan; Stopfer, Jill; Galantino, Mary Lou; Bryan, Cathy; Hwang, Wei-Ting; Schmitz, Kathryn

2016-08-01

Dysregulation of adipokines, such as adiponectin and leptin, is associated with a variety of chronic diseases, including cancer. Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels. The WISER Sister Trial was a three-armed randomized controlled trial in premenopausal women (n = 137) with an elevated risk for breast cancer. A 5-menstrual-cycle-long dosed aerobic exercise intervention compared low-dose exercise (150 min/wk; n = 44) or high-dose exercise (300 min/wk; n = 48) with a control group asked to maintain usual activity levels (n = 45). Exercise intensity progressed to and was maintained at 70% to 80% of age predicted heart rate max. Body composition and adipokine levels were measured at baseline and follow-up. We observed significant linear trends for increased fitness capacity (Δ%: -2.0% control, 10.1% low dose, 13.1% high dose), decreased fat tissue-to-total tissue mass (Δ%: 0.7% control, -2.9% low dose, -3.7% high dose), increased body fat adjusted adiponectin (Δ%: -0.6% control, 0.6% low dose, 0.9% high dose), and decreased body fat adjusted leptin (Δ%: 0.7% control, -8.2% low dose, -10.2% high dose). In this randomized clinical trial of premenopausal women at risk for breast cancer, we demonstrate a dose-response effect of exercise on adiponectin and leptin and that dose response is dependent on changes in body fat. Improved adipokine levels, achieved by aerobic exercise training-induced decreases in body fat, may decrease breast cancer risk for high-risk premenopausal women. Cancer Epidemiol Biomarkers Prev; 25(8); 1195-200. ©2016 AACR. ©2016 American Association for Cancer Research.

Stimulus-Dependent Dopamine Release in Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Sikstrom, Sverker; Soderlund, Goran

2007-01-01

Attention-deficit/hyperactivity disorder (ADHD) is related to an attenuated and dysfunctional dopamine system. Normally, a high extracellular dopamine level yields a tonic dopaminergic input that down-regulates stimuli-evoked phasic dopamine responses through autoreceptors. Abnormally low tonic extracellular dopamine in ADHD up-regulates the…

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

Heart, Emma; Palo, Meridith; Womack, Trayce

Pancreatic β-cells release insulin in response to elevation of glucose from basal (4–7 mM) to stimulatory (8–16 mM) levels. Metabolism of glucose by the β-cell results in the production of low levels of reactive oxygen intermediates (ROI), such as hydrogen peroxide (H{sub 2}O{sub 2}), a newly recognized coupling factor linking glucose metabolism to insulin secretion. However, high and toxic levels of H{sub 2}O{sub 2} inhibit insulin secretion. Menadione, which produces H{sub 2}O{sub 2} via redox cycling mechanism in a dose-dependent manner, was investigated for its effect on β-cell metabolism and insulin secretion in INS-1 832/13, a rat β-cell insulinoma cellmore » line, and primary rodent islets. Menadione-dependent redox cycling and resulting H{sub 2}O{sub 2} production under stimulatory glucose exceeded several-fold those reached at basal glucose. This was paralleled by a differential effect of menadione (0.1–10 μM) on insulin secretion, which was enhanced at basal, but inhibited at stimulatory glucose. Redox cycling of menadione and H{sub 2}O{sub 2} formation was dependent on glycolytically-derived NADH, as inhibition of glycolysis and application of non-glycogenic insulin secretagogues did not support redox cycling. In addition, activity of plasma membrane electron transport, a system dependent in part on glycolytically-derived NADH, was also inhibited by menadione. Menadione-dependent redox cycling was sensitive to the NQO1 inhibitor dicoumarol and the flavoprotein inhibitor diphenylene iodonium, suggesting a role for NQO1 and other oxidoreductases in this process. These data may explain the apparent dichotomy between the stimulatory and inhibitory effects of H{sub 2}O{sub 2} and menadione on insulin secretion. -- Highlights: ► Menadione stimulation or inhibition of insulin secretion is dependent upon applied glucose levels. ► Menadione-dependent H{sub 2}O{sub 2} production is proportional to applied glucose levels. ► Quinone-mediated redox cycling is dependent on glycolysis.« less

Effect of atmospheric carbon dioxide levels and nitrate fertilization on glucosinolate biosynthesis in mechanically damaged Arabidopsis plants.

PubMed

Paudel, Jamuna Risal; Amirizian, Alexandre; Krosse, Sebastian; Giddings, Jessica; Ismail, Shoieb Akaram Arief; Xia, Jianguo; Gloer, James B; van Dam, Nicole M; Bede, Jacqueline C

2016-03-22

Increased atmospheric carbon dioxide (CO2) levels predicted to occur before the end of the century will impact plant metabolism. In addition, nitrate availability will affect metabolism and levels of nitrogen-containing defense compounds, such as glucosinolates (GSLs). We compared Arabidopsis foliar metabolic profile in plants grown under two CO2 regimes (440 vs 880 ppm), nitrate fertilization (1 mM vs 10 mM) and in response to mechanical damage of rosette leaves. Constitutive foliar metabolites in nitrate-limited plants show distinct global patterns depending on atmospheric CO2 levels; in contrast, plants grown under higher nitrate fertilization under elevated atmospheric CO2 conditions have a unique metabolite signature. Nitrate fertilization dampens the jasmonate burst in response to wounding in plants grown at elevated CO2 levels. Leaf GSL profile mirrors the jasmonate burst; in particular, indole GSLs increase in response to damage in plants grown at ambient CO2 but only in nitrate-limited plants grown under elevated CO2 conditions. This may reflect a reduced capacity of C3 plants grown under enriched CO2 and nitrate levels to signal changes in oxidative stress and has implications for future agricultural management practices.

The flip side of immune surveillance: immune dependency.

PubMed

Prehn, Richmond T; Prehn, Liisa M

2008-04-01

The growths of many and perhaps all tumors may be stimulated rather than inhibited by a quantitatively low level of immunity. The reason tumors have antigens may be that tumors do not develop in vivo in the absence of at least a minimal immune reaction; in this sense, cancer may be considered an autoimmune disease. This review, based largely on the work of our own laboratory, outlines the data showing that the titration of anti-tumor immunity exhibits the phenomenon of hormesis, i.e. the dose-response curve is non-linear such that low levels of immunity are generally stimulatory but larger quantities of the same immune reactants may inhibit tumor growth. Evidence is also reviewed that suggests that the immune response may vary qualitatively and quantitatively during progression, such that there seems to be, during oncogenesis, a very low level of immune reaction that aids initial tumor growth, followed by a larger reaction that may cause remission of early neoplasms, followed, if the neoplasm survives, by a relative immunologic tolerance to the tumor that may be dependent, at least in part, on suppressor cells. This knowledge may help to explain some clinical observations concerning the relationships among tumor types and the organ distribution of metastases.

Experience-Dependent Effects of Cocaine Self-Administration/Conditioning on Prefrontal and Accumbens Dopamine Responses

PubMed Central

Ikegami, Aiko; Olsen, Christopher M.; D’Souza, Manoranjan S.; Duvauchelle, Christine L.

2008-01-01

Experiments were performed to examine the effects of cocaine self-administration and conditioning experience on operant behavior, locomotor activity, and nucleus accumbens (NAcc) and prefrontal cortex (PFC) dopamine (DA) responses. Sensory cues were paired with alternating cocaine and nonreinforcement during 12 (limited training) or 40 (long-term training) daily operant sessions. After limited training, NAcc DA responses to cocaine were significantly enhanced in the presence of cocaine-associated cues compared with nonreward cues and significantly depressed after cocaine-paired cues accompanied a nonreinforced lever response. PFC DA levels were generally nonresponsive to cues after the same training duration. However, after long-term training, cocaine-associated cues increased the magnitude of cocaine-stimulated PFC DA levels significantly over levels observed with nonreinforcement cues. Conversely, conditioned cues no longer influenced NAcc DA levels after long-term training. In addition, cocaine-stimulated locomotor activity was enhanced by cocaine-paired cues after long-term, but not after limited, training. Findings demonstrate that cue-induced cocaine expectation exerts a significant impact on dopaminergic and behavioral systems, progressing from mesolimbic to mesocortical regions and from latent to patent behaviors as cocaine and associative experiences escalate. PMID:17469929

Metabolomic Responses of Arabidopsis Suspension Cells to Bicarbonate under Light and Dark Conditions

PubMed Central

Misra, Biswapriya B.; Yin, Zepeng; Geng, Sisi; de Armas, Evaldo; Chen, Sixue

2016-01-01

Global CO2 level presently recorded at 400 ppm is expected to reach 550 ppm in 2050, an increment likely to impact plant growth and productivity. Using targeted LC-MS and GC-MS platforms we quantified 229 and 29 metabolites, respectively in a time-course study to reveal short-term responses to different concentrations (1, 3, and 10 mM) of bicarbonate (HCO3−) under light and dark conditions. Results indicate that HCO3− treatment responsive metabolomic changes depend on the HCO3− concentration, time of treatment, and light/dark. Interestingly, 3 mM HCO3− concentration treatment induced more significantly changed metabolites than either lower or higher concentrations used. Flavonoid biosynthesis and glutathione metabolism were common to both light and dark-mediated responses in addition to showing concentration-dependent changes. Our metabolomics results provide insights into short-term plant cellular responses to elevated HCO3− concentrations as a result of ambient increases in CO2 under light and dark. PMID:27762345

Effects of elevated dissolved carbon dioxide and perfluorooctane sulfonic acid, given singly and in combination, on steroidogenic and biotransformation pathways of Atlantic cod.

PubMed

Preus-Olsen, Gunnhild; Olufsen, Marianne O; Pedersen, Sindre Andre; Letcher, Robert J; Arukwe, Augustine

2014-10-01

In the aquatic environments, the predicted changes in water temperature, pO2 and pCO2 could result in hypercapnic and hypoxic conditions for aquatic animals. These conditions are thought to affect several basic cellular and physiological mechanisms. Yet, possible adverse effects of elevated CO2 (hypercapnia) on teleost fish, as well as combined effects with emerging and legacy environmental contaminants are poorly investigated. In this study, juvenile Atlantic cod (Gadus morhua) were divided into groups and exposed to three different water bath PFOS exposure regimes (0 (control), 100 and 200 μg L(-1)) for 5 days at 1h/day, followed by three different CO2-levels (normocapnia, moderate (0.3%) and high (0.9%)). The moderate CO2 level is the predicted near future (within year 2300) level, while 0.9% represent severe hypercapnia. Tissue samples were collected at 3, 6 and 9 days after initiated CO2 exposure. Effects on the endocrine and biotransformation systems were examined by analyzing levels of sex steroid hormones (E2, T, 11-KT) and transcript expression of estrogen responsive genes (ERα, Vtg-α, Vtg-β, ZP2 and ZP3). In addition, transcripts for genes encoding xenobiotic metabolizing enzymes (cyp1a and cyp3a) and hypoxia-inducible factor (HIF-1α) were analyzed. Hypercapnia alone produced increased levels of sex steroid hormones (E2, T, 11-KT) with concomitant mRNA level increase of estrogen responsive genes, while PFOS produced weak and time-dependent effects on E2-inducible gene transcription. Combined PFOS and hypercapnia exposure produced increased effects on sex steroid levels as compared to hypercapnia alone, with transcript expression patterns that are indicative of time-dependent interactive effects. Exposure to hypercapnia singly or in combination with PFOS produced modulations of the biotransformation and hypoxic responses that were apparently concentration- and time-dependent. Loading plots of principal component analysis (PCA) produced a significant grouping of individual scores according to the exposure scenarios at day 6 and 9. Overall, the PCA analysis produced a unique clustering of variables that signifies a positive correlation between exposure to high PFOS concentration and mRNA expression of E2 responsive genes. Notably, this pattern was not evident for individuals exposed to PFOS concentrations in combination with elevated CO2 scenarios. To our knowledge, the present study is the first of its kind, to evaluate such effects using combined exposure to a perfluoroalkyl sulfonate and elevated levels of CO2 saturation, representative of future oceanic climate change, in any fish species or lower vertebrate. Copyright © 2014 Elsevier B.V. All rights reserved.

Hes1 promotes the IL-22-mediated antimicrobial response by enhancing STAT3-dependent transcription in human intestinal epithelial cells

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

Murano, Tatsuro; Okamoto, Ryuichi, E-mail: rokamoto.gast@tmd.ac.jp; Department of Advanced GI Therapeutics, Graduate School, Tokyo Medical and Dental University, Tokyo

Highlights: •Hes1 enhances IL-22-STAT3 signaling in human intestinal epithelial cells. •Hes1 enhances REG family gene induction by IL-22-STAT3 signaling. •Protein level of Hes1 restricts the response to IL-22. •Present regulation of a cytokine signal represents a new mode of Hes1 function. -- Abstract: Notch signaling plays an essential role in the proliferation and differentiation of intestinal epithelial cells (IECs). We have previously shown that Notch signaling is up-regulated in the inflamed mucosa of ulcerative colitis (UC) and thereby plays an indispensable role in tissue regeneration. Here we show that in addition to Notch signaling, STAT3 signaling is highly activated inmore » the inflamed mucosa of UC. Forced expression of the Notch target gene Hes1 dramatically enhanced the IL-22-mediated STAT3-dependent transcription in human IECs. This enhancement of STAT3-dependent transcription was achieved by the extended phosphorylation of STAT3 by Hes1. Microarray analysis revealed that Hes1-mediated enhancement of IL-22-STAT3 signaling significantly increased the induction of genes encoding antimicrobial peptides, such as REG1A, REG3A and REG3G, in human IECs. Conversely, the reduction of Hes1 protein levels with a γ-secretase inhibitor significantly down-regulated the induction of those genes in IECs, resulting in a markedly poor response to IL-22. Our present findings identify a new role for the molecular function of Hes1 in which the protein can interact with cytokine signals and regulate the immune response of IECs.« less

Regional entropy of functional imaging signals varies differently in sensory and cognitive systems during propofol-modulated loss and return of behavioral responsiveness.

PubMed

Liu, Xiaolin; Lauer, Kathryn K; Ward, B Douglas; Roberts, Christopher J; Liu, Suyan; Gollapudy, Suneeta; Rohloff, Robert; Gross, William; Xu, Zhan; Chen, Shanshan; Wang, Lubin; Yang, Zheng; Li, Shi-Jiang; Binder, Jeffrey R; Hudetz, Anthony G

2018-05-08

The level and richness of consciousness depend on information integration in the brain. Altered interregional functional interactions may indicate disrupted information integration during anesthetic-induced unconsciousness. How anesthetics modulate the amount of information in various brain regions has received less attention. Here, we propose a novel approach to quantify regional information content in the brain by the entropy of the principal components of regional blood oxygen-dependent imaging signals during graded propofol sedation. Fifteen healthy individuals underwent resting-state scans in wakeful baseline, light sedation (conscious), deep sedation (unconscious), and recovery (conscious). Light sedation characterized by lethargic behavioral responses was associated with global reduction of entropy in the brain. Deep sedation with completely suppressed overt responsiveness was associated with further reductions of entropy in sensory (primary and higher sensory plus orbital prefrontal cortices) but not high-order cognitive (dorsal and medial prefrontal, cingulate, parietotemporal cortices and hippocampal areas) systems. Upon recovery of responsiveness, entropy was restored in the sensory but not in high-order cognitive systems. These findings provide novel evidence for a reduction of information content of the brain as a potential systems-level mechanism of reduced consciousness during propofol anesthesia. The differential changes of entropy in the sensory and high-order cognitive systems associated with losing and regaining overt responsiveness are consistent with the notion of "disconnected consciousness", in which a complete sensory-motor disconnection from the environment occurs with preserved internal mentation.

Possible relationship between the stress-induced synaptic response and metaplasticity in the hippocampal CA1 field of freely moving rats.

PubMed

Hirata, Riki; Matsumoto, Machiko; Judo, Chika; Yamaguchi, Taku; Izumi, Takeshi; Yoshioka, Mitsuhiro; Togashi, Hiroko

2009-07-01

Hippocampal long-term potentiation (LTP) is suppressed not only by stress paradigms but also by low frequency stimulation (LFS) prior to LTP-inducing high frequency stimulation (HFS; tetanus), termed metaplasticity. These synaptic responses are dependent on N-methyl-D-aspartate receptors, leading to speculations about the possible relationship between metaplasticity and stress-induced LTP impairment. However, the functional significance of metaplasticity has been unclear. The present study elucidated the electrophysiological and neurochemical profiles of metaplasticity in the hippocampal CA1 field, with a focus on the synaptic response induced by the emotional stress, contextual fear conditioning (CFC). The population spike amplitude in the CA1 field was decreased during exposure to CFC, and LTP induction was suppressed after CFC in conscious rats. The synaptic response induced by CFC was mimicked by LFS, i.e., LFS impaired the synaptic transmission and subsequent LTP. Plasma corticosterone levels were increased by both CFC and LFS. Extracellular levels of gamma-aminobutyric acid (GABA), but not glutamate, in the hippocampus increased during exposure to CFC or LFS. Furthermore, electrical stimulation of the medial prefrontal cortex (mPFC), which caused decreases in freezing behavior during exposure to CFC, counteracted the LTP impairment induced by LFS. These findings suggest that metaplasticity in the rat hippocampal CA1 field is related to the neural basis of stress experience-dependent fear memory, and that hippocampal synaptic response associated stress-related processes is under mPFC regulation.

Iron and oxygen sensing: a tale of 2 interacting elements?

PubMed

Simpson, Robert J; McKie, Andrew T

2015-02-01

Iron and oxygen metabolism are intimately linked with one another. A change in the level of either metabolite results in activation of common pathways. At the heart of these responses lies a group of iron and oxygen dependent enzymes called prolyl hydroxylases. Prolyl hydroxylases (PHDs) require both iron and oxygen for optimal activity and their biological activity is to carry out the critical post-translational modification of the addition of a hydroxyl group to specific proline residues within Hypoxia Inducible Factor (HIFs)-well known transcription factors originally thought to regulate responses to hypoxia but which are now known to regulate key iron metabolism proteins too. The addition of the hydroxyl group ultimately leads to the unbiquitylation and destruction of HIFs, thus PHDs control appropriate HIF transcriptional responses depending on cellular oxygen or iron levels. There are two major HIFs; HIF1α and HIF2α. In terms of responses to iron HIF2α is of major importance in key tissues such as the intestine where several iron transporters (Ferroportin, Dcytb) contain HREs within their promoters which bind HIF2α. Furthermore the recent discovery that HIF2α contains a 5' iron responsive element (IRE) has underlined the importance of HIF2α as a major player in iron metabolism. This review brings together recent findings with regard to the HIF2α/IRP network as well as other aspects of iron sensing in cells and tissues.

Chloral hydrate-dependent reduction in the peptidoglycan-induced inflammatory macrophage response is associated with lower expression levels of toll-like receptor 2.

PubMed

Pan, Qingjun; Liu, Yuan; Zhu, Xuezhi; Liu, Huafeng

2014-05-01

The aim of this study was to investigate the effect and mechanism of action of chloral hydrate on the peptidoglycan (PGN)-induced inflammatory macrophage response. The effect of chloral hydrate on the production of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) by murine peritoneal macrophages with PGN-stimulation was investigated. In addition, RAW264.7 cells transfected with a nuclear factor-κB (NF-κB) luciferase reporter plasmid stimulated by PGN were used to study the effect of chloral hydrate on the levels NF-κB activity. Flow cytometry and western blotting were performed to investigate the expression levels of toll-like receptor 2 (TLR2) in the treated RAW264.7 cells. It was identified that chloral hydrate reduced the levels of IL-6 and TNF-α produced by the peritoneal macrophages stimulated with PGN. The levels of NF-κB activity of the RAW264.7 cells stimulated by PGN decreased following treatment with chloral hydrate, which was associated with a reduction in the expression levels of TLR2 and reduced levels of TLR2 signal transduction. These data demonstrate that chloral hydrate reduced the magnitude of the PGN-induced inflammatory macrophage response associated with lower expression levels of TLR2.

Non-tip auditory-nerve responses that are suppressed by low-frequency bias tones originate from reticular lamina motion.

PubMed

Nam, Hui; Guinan, John J

2017-12-14

Recent cochlear mechanical measurements show that active processes increase the motion response of the reticular lamina (RL) at frequencies more than an octave below the local characteristic frequency (CF) for CFs above 5 kHz. A possible correlate is that in high-CF (>5 kHz) auditory-nerve (AN) fibers, responses to frequencies 1-3 octaves below CF ("tail" frequencies) can be inhibited by medial olivocochlear (MOC) efferents. These results indicate that active processes enhance the sensitivity of tail-frequency RL and AN responses. Perhaps related is that some apical low-CF AN fibers have tuning-curve (TC) "side-lobe" response areas at frequencies above and below the TC-tip that are MOC inhibited. We hypothesized that the tail and side-lobe responses are enhanced by the same active mechanisms as CF cochlear amplification. If responses to CF, tail-frequency, and TC-side-lobe tones are all enhanced by prestin motility controlled by outer-hair-cell (OHC) transmembrane voltage, then they should depend on OHC stereocilia position in the same way. To test this, we cyclically changed the OHC-stereocilia mechano-electric-transduction (MET) operating point with low-frequency "bias" tones (BTs) and increased the BT level until the BT caused quasi-static OHC MET saturation that reduced or "suppressed" the gain of OHC active processes. While measuring cat AN-fiber responses, 50 Hz BT level series, 70-120 dB SPL, were run alone and with CF tones, or 2.5 kHz tail-frequency tones, or side-lobe tones. BT-tone-alone responses were used to exclude BT sound levels that produced AN responses that might obscure BT suppression. Data were analyzed to show the BT phase that suppressed the tone responses at the lowest sound level. We found that AN responses to CF, tail-frequency, and side-lobe tones were suppressed at the same BT phase in almost all cases. The data are consistent with the enhancement of responses to CF, tail-frequency, and side-lobe tones all being due to the same OHC-stereocilia MET-dependent active process. Thus, OHC active processes enhance AN responses at frequencies outside of the cochlear-amplified TC-tip region in both high- and low-frequency cochlear regions. The data are consistent with the AN response enhancements being due to enhanced RL motion that drives IHC-stereocilia deflection by traditional RL-TM shear and/or by changing the RL-TM gap. Since tail-frequency basilar membrane (BM) motion is not actively enhanced, the tail-frequency IHC drive is from a vibrational mode little present on the BM, not a "second filter" of BM motion. Copyright © 2017 Elsevier B.V. All rights reserved.

Beta-endorphin-induced inhibition and stimulation of insulin secretion in normal humans is glucose dependent.

PubMed

Giugliano, D; Cozzolino, D; Salvatore, T; Torella, R; D'Onofrio, F

1988-09-01

This study evaluated the effect of human beta-endorphin on pancreatic hormone levels and their responses to nutrient challenges in normal subjects. Infusion of 0.5 mg/h beta-endorphin caused a significant rise in plasma glucose concentrations preceded by a significant increase in peripheral glucagon levels. No changes occurred in the plasma concentrations of insulin and C-peptide. Acute insulin and C-peptide responses to intravenous pulses of different glucose amounts (0.33 g/kg and 5 g) and arginine (3 g) were significantly reduced by beta-endorphin infusion (P less than .01). This effect was associated with a significant reduction of the glucose disappearance rates, suggesting that the inhibition of insulin was of biological relevance. beta-Endorphin also inhibited glucose suppression of glucagon levels and augmented the glucagon response to arginine. To verify whether the modification of prestimulus glucose level could be important in these hormonal responses to beta-endorphin, basal plasma glucose concentrations were raised by a primed (0.5 g/kg) continuous (20 mg kg-1.min-1) glucose infusion. After stabilization of plasma glucose levels (350 +/- 34 mg/dl, t = 120 min), beta-endorphin infusion caused an immediate and marked increase in plasma insulin level (peak response 61 +/- 9 microU/ml, P less than .01), which remained elevated even after the discontinuation of opioid infusion. Moreover, the acute insulin response to a glucose pulse (0.33 g/kg i.v.) given during beta-endorphin infusion during hyperglycemia was significantly higher than the response obtained during euglycemia (171 +/- 32 vs. 41 +/- 7 microU/ml, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of phosphorylated Apis mellifera CREB in gating a honeybee's behavioral response to an external stimulus

PubMed Central

Gehring, Katrin B.; Heufelder, Karin; Feige, Janina; Bauer, Paul; Dyck, Yan; Ehrhardt, Lea; Kühnemund, Johannes; Bergmann, Anja; Göbel, Josefine; Isecke, Marlene

2016-01-01

The transcription factor cAMP-response element-binding protein (CREB) is involved in neuronal plasticity. Phosphorylation activates CREB and an increased level of phosphorylated CREB is regarded as an indicator of CREB-dependent transcriptional activation. In honeybees (Apis mellifera) we recently demonstrated a particular high abundance of the phosphorylated honeybee CREB homolog (pAmCREB) in the central brain and in a subpopulation of mushroom body neurons. We hypothesize that these high pAmCREB levels are related to learning and memory formation. Here, we tested this hypothesis by analyzing brain pAmCREB levels in classically conditioned bees and bees experiencing unpaired presentations of conditioned stimulus (CS) and unconditioned stimulus (US). We demonstrate that both behavioral protocols display differences in memory formation but do not alter the level of pAmCREB in bee brains directly after training. Nevertheless, we report that bees responding to the CS during unpaired stimulus presentations exhibit higher levels of pAmCREB than nonresponding bees. In addition, Trichostatin A, a histone deacetylase inhibitor that is thought to enhance histone acetylation by CREB-binding protein, increases the bees’ CS responsiveness. We conclude that pAmCREB is involved in gating a bee's behavioral response driven by an external stimulus. PMID:27084927

TAS2R bitter taste receptors regulate thyroid function

PubMed Central

Clark, Adam A.; Dotson, Cedrick D.; Elson, Amanda E. T.; Voigt, Anja; Boehm, Ulrich; Meyerhof, Wolfgang; Steinle, Nanette I.; Munger, Steven D.

2015-01-01

Dysregulation of thyroid hormones triiodothyronine and thyroxine (T3/T4) can impact metabolism, body composition, and development. Thus, it is critical to identify novel mechanisms that impact T3/T4 production. We found that type 2 taste receptors (TAS2Rs), which are activated by bitter-tasting compounds such as those found in many foods and pharmaceuticals, negatively regulate thyroid-stimulating hormone (TSH)-dependent Ca2+ increases and TSH-dependent iodide efflux in thyrocytes. Immunohistochemical Tas2r-dependent reporter expression and real-time PCR analyses reveal that human and mouse thyrocytes and the Nthy-Ori 3-1 human thyrocyte line express several TAS2Rs. Five different agonists for thyrocyte-expressed TAS2Rs reduced TSH-dependent Ca2+ release in Nthy-Ori 3-1 cells, but not basal Ca2+ levels, in a dose-dependent manner. Ca2+ responses were unaffected by 6-n-propylthiouracil, consistent with the expression of an unresponsive variant of its cognate receptor, TAS2R38, in these cells. TAS2R agonists also inhibited basal and TSH-dependent iodide efflux. Furthermore, a common TAS2R42 polymorphism is associated with increased serum T4 levels in a human cohort. Our findings indicate that TAS2Rs couple the detection of bitter-tasting compounds to changes in thyrocyte function and T3/T4 production. Thus, TAS2Rs may mediate a protective response to overingestion of toxic materials and could serve as new druggable targets for therapeutic treatment of hypo- or hyperthyroidism.—Clark, A. A., Dotson, C. D., Elson, A. E. T., Voigt, A., Boehm, U., Meyerhof, W., Steinle, N. I., Munger, S. D. TAS2R bitter taste receptors regulate thyroid function. PMID:25342133

GPR55 agonist lysophosphatidylinositol and lysophosphatidylcholine inhibit endothelial cell hyperpolarization via GPR-independent suppression of Na+-Ca2+ exchanger and endoplasmic reticulum Ca2+ refilling.

PubMed

Bondarenko, Alexander I; Montecucco, Fabrizio; Panasiuk, Olga; Sagach, Vadim; Sidoryak, Nataliya; Brandt, Karim J; Mach, François

2017-02-01

Lysophosphatidylinositol (LPI) and lysophosphatidylcholine (LPC) are lipid signaling molecules that induce endothelium-dependent vasodilation. In addition, LPC suppresses acetylcholine (Ach)-induced responses. We aimed to determine the influence of LPC and LPI on hyperpolarizing responses in vitro and in situ endothelial cells (EC) and identify the underlying mechanisms. Using patch-clamp method, we show that LPI and LPC inhibit EC hyperpolarization to histamine and suppress Na + /Ca 2+ exchanged (NCX) currents in a concentration-dependent manner. The inhibition is non-mode-specific and unaffected by intracellular GDPβS infusion and tempol, a superoxide dismutase mimetic. In excised mouse aorta, LPI strongly inhibits the sustained and the peak endothelial hyperpolarization induced by Ach, but not by SKA-31, an opener of Ca 2+ -dependent K + channels of intermediate and small conductance. The hyperpolarizing responses to consecutive histamine applications are strongly reduced by NCX inhibition. In a Ca 2+ -re-addition protocol, bepridil, a NCX inhibitor, and KB-R7943, a blocker of reversed NCX, inhibit the hyperpolarizing responses to Ca 2+ -re-addition following Ca 2+ stores depletion. These finding indicate that LPC and LPI inhibit endothelial hyperpolarization to Ach and histamine independently of G-protein coupled receptors and superoxide anions. Reversed NCX is critical for ER Ca 2+ refilling in EC. The inhibition of NCX by LPI and LPC underlies diminished endothelium-dependent responses and endothelial dysfunction accompanied by increased levels of these lipids in the blood. Copyright © 2017 Elsevier Inc. All rights reserved.

Fast fMRI can detect oscillatory neural activity in humans.

PubMed

Lewis, Laura D; Setsompop, Kawin; Rosen, Bruce R; Polimeni, Jonathan R

2016-10-25

Oscillatory neural dynamics play an important role in the coordination of large-scale brain networks. High-level cognitive processes depend on dynamics evolving over hundreds of milliseconds, so measuring neural activity in this frequency range is important for cognitive neuroscience. However, current noninvasive neuroimaging methods are not able to precisely localize oscillatory neural activity above 0.2 Hz. Electroencephalography and magnetoencephalography have limited spatial resolution, whereas fMRI has limited temporal resolution because it measures vascular responses rather than directly recording neural activity. We hypothesized that the recent development of fast fMRI techniques, combined with the extra sensitivity afforded by ultra-high-field systems, could enable precise localization of neural oscillations. We tested whether fMRI can detect neural oscillations using human visual cortex as a model system. We detected small oscillatory fMRI signals in response to stimuli oscillating at up to 0.75 Hz within single scan sessions, and these responses were an order of magnitude larger than predicted by canonical linear models. Simultaneous EEG-fMRI and simulations based on a biophysical model of the hemodynamic response to neuronal activity suggested that the blood oxygen level-dependent response becomes faster for rapidly varying stimuli, enabling the detection of higher frequencies than expected. Accounting for phase delays across voxels further improved detection, demonstrating that identifying vascular delays will be of increasing importance with higher-frequency activity. These results challenge the assumption that the hemodynamic response is slow, and demonstrate that fMRI has the potential to map neural oscillations directly throughout the brain.

Light Levels Affect Carbon Utilisation in Tropical Seagrass under Ocean Acidification.

PubMed

Ow, Yan X; Uthicke, Sven; Collier, Catherine J

2016-01-01

Under future ocean acidification (OA), increased availability of dissolved inorganic carbon (DIC) in seawater may enhance seagrass productivity. However, the ability to utilise additional DIC could be regulated by light availability, often reduced through land runoff. To test this, two tropical seagrass species, Cymodocea serrulata and Halodule uninervis were exposed to two DIC concentrations (447 μatm and 1077 μatm pCO2), and three light treatments (35, 100, 380 μmol m(-2) s(-1)) for two weeks. DIC uptake mechanisms were separately examined by measuring net photosynthetic rates while subjecting C. serrulata and H. uninervis to changes in light and addition of bicarbonate (HCO3-) use inhibitors (carbonic anhydrase inhibitor, acetazolamide) and TRIS buffer (pH 8.0). We observed a strong dependence on energy driven H+-HCO3- co-transport (TRIS, which disrupts H+ extrusion) in C. serrulata under all light levels, indicating greater CO2 dependence in low light. This was confirmed when, after two weeks exposure, DIC enrichment stimulated maximum photosynthetic rates (Pmax) and efficiency (α) more in C. serrulata grown under lower light levels (36-60% increase) than for those in high light (4% increase). However, C. serrulata growth increased with both DIC enrichment and light levels. Growth, NPP and photosynthetic responses in H. uninervis increased with higher light treatments and were independent of DIC availability. Furthermore, H. uninervis was found to be more flexible in HCO3- uptake pathways. Here, light availability influenced productivity responses to DIC enrichment, via both carbon fixation and acquisition processes, highlighting the role of water quality in future responses to OA.

Light Levels Affect Carbon Utilisation in Tropical Seagrass under Ocean Acidification

PubMed Central

2016-01-01

Under future ocean acidification (OA), increased availability of dissolved inorganic carbon (DIC) in seawater may enhance seagrass productivity. However, the ability to utilise additional DIC could be regulated by light availability, often reduced through land runoff. To test this, two tropical seagrass species, Cymodocea serrulata and Halodule uninervis were exposed to two DIC concentrations (447 μatm and 1077 μatm pCO2), and three light treatments (35, 100, 380 μmol m-2 s-1) for two weeks. DIC uptake mechanisms were separately examined by measuring net photosynthetic rates while subjecting C. serrulata and H. uninervis to changes in light and addition of bicarbonate (HCO3-) use inhibitors (carbonic anhydrase inhibitor, acetazolamide) and TRIS buffer (pH 8.0). We observed a strong dependence on energy driven H+-HCO3- co-transport (TRIS, which disrupts H+ extrusion) in C. serrulata under all light levels, indicating greater CO2 dependence in low light. This was confirmed when, after two weeks exposure, DIC enrichment stimulated maximum photosynthetic rates (Pmax) and efficiency (α) more in C. serrulata grown under lower light levels (36–60% increase) than for those in high light (4% increase). However, C. serrulata growth increased with both DIC enrichment and light levels. Growth, NPP and photosynthetic responses in H. uninervis increased with higher light treatments and were independent of DIC availability. Furthermore, H. uninervis was found to be more flexible in HCO3- uptake pathways. Here, light availability influenced productivity responses to DIC enrichment, via both carbon fixation and acquisition processes, highlighting the role of water quality in future responses to OA. PMID:26938454

Plasma growth hormone (GH), insulin and amino acid responses to arginine with or without aspartic acid in pigs. Effect of the dose.

PubMed

Cochard, A; Guilhermet, R; Bonneau, M

1998-01-01

The aim of the present study was to examine, for the first time in pigs, the dose-dependent effect of arginine (ARG) on growth hormone (GH) and insulin release and the effect of the combined ARG and aspartic acid (ASP) treatment on GH and insulin release. ARG (0.5 or 1 g/kg body weight) with or without an equimolar supplement of ASP (0.38 or 0.76 g/kg, respectively) was administered in piglets via the duodenum. ARG increased plasma arginine, ornithine, urea, proline and branched chain amino acid concentrations. ASP increased specifically plasma aspartic acid, glutamic acid, alanine and citrulline concentrations. Plasma insulin increased with no apparent difference between treatments. Maximum GH level and the area under the GH curve (AUC) were increased in a dose-dependent manner in response to ARG treatment. GH response to the combined ARG and ASP treatment (ARGASP) was delayed compared to ARG alone and was not dose-dependent. AUC for GH after ARGASP treatments were intermediate between those observed after the two ARG doses. Our data suggest that high ASP doses transiently inhibit and delay ARG-induced GH release in pigs and that an equimolar supplement of ASP stimulates or inhibits ARG-induced GH release depending on the dose used.

fMRI BOLD response to the eyes task in offspring from multiplex alcohol dependence families.

PubMed

Hill, Shirley Y; Kostelnik, Bryan; Holmes, Brian; Goradia, Dhruman; McDermott, Michael; Diwadkar, Vaibhav; Keshavan, Matcheri

2007-12-01

Increased susceptibility for developing alcohol dependence (AD) may be related to structural and functional differences in brain circuits that influence social cognition and more specifically, theory of mind (ToM). Alcohol dependent individuals have a greater likelihood of having deficits in social skills and greater social alienation. These characteristics may be related to inherited differences in the neuroanatomical network that comprises the social brain. Adolescent/young adult participants from multiplex AD families and controls (n = 16) were matched for gender, age, IQ, education, and handedness and administered the Eyes Task of Baron-Cohen during functional magnetic resonance imaging (fMRI). High-risk (HR) subjects showed significantly diminished blood oxygen level dependent (BOLD) response in comparison with low-risk control young adults in the right middle temporal gyrus (RMTG) and the left inferior frontal gyrus (LIFG), areas that have previously been implicated in ToM tasks. Offspring from multiplex families for AD may manifest one aspect of their genetic susceptibility by having a diminished BOLD response in brain regions associated with performance of ToM tasks. These results suggest that those at risk for developing AD may have reduced ability to empathize with others' state of mind, possibly resulting in diminished social skill.

PITX1, a specificity determinant in the HIF-1α-mediated transcriptional response to hypoxia

PubMed Central

Mudie, Sharon; Bandarra, Daniel; Batie, Michael; Biddlestone, John; Moniz, Sonia; Ortmann, Brian; Shmakova, Alena; Rocha, Sonia

2014-01-01

Hypoxia is an important developmental cue for multicellular organisms but it is also a contributing factor for several human pathologies, such as stroke, cardiovascular diseases and cancer. In cells, hypoxia activates a major transcriptional program coordinated by the Hypoxia Inducible Factor (HIF) family. HIF can activate more than one hundred targets but not all of them are activated at the same time, and there is considerable cell type variability. In this report we identified the paired-like homeodomain pituitary transcription factor (PITX1), as a transcription factor that helps promote specificity in HIF-1α dependent target gene activation. Mechanistically, PITX1 associates with HIF-1β and it is important for the induction of certain HIF-1 dependent genes but not all. In particular, PITX1 controls the HIF-1α-dependent expression of the histone demethylases; JMJD2B, JMJD2A, JMJD2C and JMJD1B. Functionally, PITX1 is required for the survival and proliferation responses in hypoxia, as PITX1 depleted cells have higher levels of apoptotic markers and reduced proliferation. Overall, our study identified PITX1 as a key specificity factor in HIF-1α dependent responses, suggesting PITX1 as a protein to target in hypoxic cancers. PMID:25558831

Response to phytohaemagglutinin of lymphocytes from mice treated with anti-lymphocyte globulin

PubMed Central

Tursi, A.; Greaves, M. F.; Torrigiani, G.; Playfair, J. H. L.; Roitt, I. M.

1969-01-01

Thymus, spleen, lymph node and peripheral blood lymphocytes taken from mice treated with anti-lymphocyte globulin (ALG) showed a greatly diminished response to PHA in vitro. Recovery of circulating lymphocyte levels preceded recovery of responsiveness to PHA. The latter could be prevented by reinjection of ALG or by thymectomy. Grafts were rejected within a period equal to the normal rejection time after PHA responsiveness had recovered to a value of approximately 20 per cent of the normal. Thus the effect of ALG on thymus dependent lymphocytes in mice can be monitored by assessing the PHA sensitivity of peripheral white blood cells. ImagesFIG. 1 PMID:4900922

A comparison of community response to aircraft noise at Toronto International and Oshawa Municipal airports†

NASA Astrophysics Data System (ADS)

Taylor, S. M.; Hall, F. L.; Birnie, S. E.

1981-07-01

Debate continues over the validity of a single dose-response relationship to describe annoyance due to transportation noise. Doubts about the appropriateness of a single relationship have centred primarily on the issue of differential response to the same noise level for different sources (e.g., aircraft, road traffic and trains). However, recent work suggests that response may vary for different types of the same source, namely aircraft, dependent upon the character, and specifically the number, of operations. Recent data collected around Toronto International and Oshawa Municipal airports permit a test of differences in four aggregate response variables. For the same NEF level, the percent at all annoyed at the two airports is not statistically different. The percent highly annoyed and the percent reporting speech interference are both significantly greater at Toronto but the percent reporting sleep interruption is greater at Oshawa. These differences can be explained in terms of the operational characteristics of the two airports.

Inhibition of Microprocessor Function during the Activation of the Type I Interferon Response.

PubMed

Witteveldt, Jeroen; Ivens, Alasdair; Macias, Sara

2018-06-12

Type I interferons (IFNs) are central components of the antiviral response. Most cell types respond to viral infections by secreting IFNs, but the mechanisms that regulate correct expression of these cytokines are not completely understood. Here, we show that activation of the type I IFN response regulates the expression of miRNAs in a post-transcriptional manner. Activation of IFN expression alters the binding of the Microprocessor complex to pri-miRNAs, reducing its processing rate and thus leading to decreased levels of a subset of mature miRNAs in an IRF3-dependent manner. The rescue of Microprocessor function during the antiviral response downregulates the levels of IFN-β and IFN-stimulated genes. All these findings support a model by which the inhibition of Microprocessor activity is an essential step to induce a robust type I IFN response in mammalian cells. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Molecular mode of action of NKP-1339 - a clinically investigated ruthenium-based drug - involves ER- and ROS-related effects in colon carcinoma cell lines.

PubMed

Flocke, Lea S; Trondl, Robert; Jakupec, Michael A; Keppler, Bernhard K

2016-06-01

Sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (NKP-1339) is a clinically investigated ruthenium-based metal complex, which shows promising results in solid tumors, such as non-small cell lung cancer, colorectal carcinoma, and most distinctively in gastrointestinal neuroendocrine tumors. In previous studies, fast binding to albumin as well as transferrin could be shown. The enhanced permeability and retention (EPR) effect, which is diversely being exploited for tumor targeting, could therefore be applicable for NKP-1339. Here we studied the serum dependence of its biological activity in various methods, influencing its cellular accumulation, cytotoxicity as well as the generation of reactive oxygen species (ROS). ROS lead to Nrf2 activation, which is known to activate antioxidant response gene transcription. GRP78 down-regulation on the protein level suggests ER associated protein degradation (ERAD) as a mode of action, as RNA levels are only mildly affected. Another important part for the mode of action is endoplasmic reticulum (ER) stress, as different factors are highly upregulated on the protein level. For example PERK, a transmembrane receptor which is released by GRP78 when the ER is disturbed, is upregulated and phosphorylated. EIF2α is phosphorylated, which leads to an inhibition of CAP-dependent translation and other stress responses. The transcription factor CHOP (DDIT3), which promotes ER stress dependent apoptosis, is time and concentration dependently upregulated. Finally cytotoxicity tests could prove that inhibition of ER stress and ER stress-mediated apoptosis leads to decreased cytotoxic effects of NKP-1339, which highlights the involvement of this mechanism in the mode of action.

Emotional arousal state influences the ability of amygdalar endocannabinoid signaling to modulate anxiety.

PubMed

Morena, Maria; Leitl, Kira D; Vecchiarelli, Haley A; Gray, J Megan; Campolongo, Patrizia; Hill, Matthew N

2016-12-01

Systemic activation of cannabinoid receptors often induces biphasic effects on emotional memory and anxiety depending on the levels of emotional arousal associated to the experimental context. The basolateral nucleus of the amygdala (BLA) represents a crucial structure for the ability of endocannabinoid (eCB) signaling to modulate emotional behaviour, and receives dense projections from brainstem arousal system nuclei. We examined whether changes in emotional arousal state would influence the ability of acute eCB manipulations within the BLA to modulate anxiety. Rats were tested in an elevated plus maze (EPM) under low or high arousal conditions. The low emotional arousal group was extensively handled and habituated to the experimental room and tested under red light condition, the high emotional arousal group was not handled or habituated and tested under high light condition. We examined amygdalar eCB anandamide (AEA) and 2-arachidonoylglycerol (2-AG) levels immediately after the EPM and the effects of intra-BLA administration of the AEA hydrolysis inhibitor URB597 or the 2-AG hydrolysis inhibitor KML29 on anxiety behaviour. The modulation of anxiety-like behaviour by eCBs in the BLA was strictly dependent on the environmental-associated emotional arousal. Pharmacologically-induced elevations of AEA or 2-AG in the BLA decreased anxiety under conditions of low emotional arousal. Conversely, when the level of emotional arousal increased, local eCB manipulation was ineffective in the modulation of the emotional arousal-induced anxiety response. These findings suggest that, depending on the emotional arousal state, eCB system is differentially activated to regulate the anxiety response in the amygdala and help to understand the state-dependency of many interventions on anxiety. Copyright © 2016. Published by Elsevier Ltd.

A Simple Model Framework to Explore the Deeply Uncertain, Local Sea Level Response to Climate Change. A Case Study on New Orleans, Louisiana

NASA Astrophysics Data System (ADS)

Bakker, Alexander; Louchard, Domitille; Keller, Klaus

2016-04-01

Sea-level rise threatens many coastal areas around the world. The integrated assessment of potential adaptation and mitigation strategies requires a sound understanding of the upper tails and the major drivers of the uncertainties. Global warming causes sea-level to rise, primarily due to thermal expansion of the oceans and mass loss of the major ice sheets, smaller ice caps and glaciers. These components show distinctly different responses to temperature changes with respect to response time, threshold behavior, and local fingerprints. Projections of these different components are deeply uncertain. Projected uncertainty ranges strongly depend on (necessary) pragmatic choices and assumptions; e.g. on the applied climate scenarios, which processes to include and how to parameterize them, and on error structure of the observations. Competing assumptions are very hard to objectively weigh. Hence, uncertainties of sea-level response are hard to grasp in a single distribution function. The deep uncertainty can be better understood by making clear the key assumptions. Here we demonstrate this approach using a relatively simple model framework. We present a mechanistically motivated, but simple model framework that is intended to efficiently explore the deeply uncertain sea-level response to anthropogenic climate change. The model consists of 'building blocks' that represent the major components of sea-level response and its uncertainties, including threshold behavior. The framework's simplicity enables the simulation of large ensembles allowing for an efficient exploration of parameter uncertainty and for the simulation of multiple combined adaptation and mitigation strategies. The model framework can skilfully reproduce earlier major sea level assessments, but due to the modular setup it can also be easily utilized to explore high-end scenarios and the effect of competing assumptions and parameterizations.

Dynamic interpretation of slug tests in highly permeable aquifers

USGS Publications Warehouse

Zurbuchen, Brian R.; Zlotnik, Vitaly A.; Butler, James J.

2002-01-01

Considerable progress has been made in developing a theoretical framework for modeling slug test responses in formations with high hydraulic conductivity K. However, several questions of practical significance remain unresolved. Given the rapid and often oscillatory nature of test responses, the traditional hydrostatic relationship between the water level and the transducer‐measured head in the water column may not be appropriate. A general dynamic interpretation is proposed that describes the relationship between water level response and transducer‐measured head. This theory is utilized to develop a procedure for transforming model‐generated water level responses to transducer readings. The magnitude of the difference between the actual water level position and the apparent position based on the transducer measurement is a function of the acceleration and velocity of the water column, test geometry, and depth of the transducer. The dynamic approach explains the entire slug test response, including the often‐noted discrepancy between the actual initial water level displacement and that measured by a transducer in the water column. Failure to use this approach can lead to a significant underestimation of K when the transducer is a considerable distance below the static water level. Previous investigators have noted a dependence of test responses on the magnitude of the initial water level displacement and have developed various approximate methods for analyzing such data. These methods are re‐examined and their limitations clarified. Practical field guidelines are proposed on the basis of findings of this work. The soundness of the dynamic approach is demonstrated through a comparison of K profiles from a series of multilevel slug tests with those from dipole‐flow tests performed in the same wells.

Synergistic airway gland mucus secretion in response to vasoactive intestinal peptide and carbachol is lost in cystic fibrosis

PubMed Central

Choi, Jae Young; Joo, Nam Soo; Krouse, Mauri E.; Wu, Jin V.; Robbins, Robert C.; Ianowski, Juan P.; Hanrahan, John W.; Wine, Jeffrey J.

2007-01-01

Cystic fibrosis (CF) is caused by dysfunction of the CF transmembrane conductance regulator (CFTR), an anion channel whose dysfunction leads to chronic bacterial and fungal airway infections via a pathophysiological cascade that is incompletely understood. Airway glands, which produce most airway mucus, do so in response to both acetylcholine (ACh) and vasoactive intestinal peptide (VIP). CF glands fail to secrete mucus in response to VIP, but do so in response to ACh. Because vagal cholinergic pathways still elicit strong gland mucus secretion in CF subjects, it is unclear whether VIP-stimulated, CFTR-dependent gland secretion participates in innate defense. It was recently hypothesized that airway intrinsic neurons, which express abundant VIP and ACh, are normally active and stimulate low-level gland mucus secretion that is a component of innate mucosal defenses. Here we show that low levels of VIP and ACh produced significant mucus secretion in human glands via strong synergistic interactions; synergy was lost in glands of CF patients. VIP/ACh synergy also existed in pig glands, where it was CFTR dependent, mediated by both Cl– and HCO3–, and clotrimazole sensitive. Loss of “housekeeping” gland mucus secretion in CF, in combination with demonstrated defects in surface epithelia, may play a role in the vulnerability of CF airways to bacterial infections. PMID:17853942

Starvation, Together with the SOS Response, Mediates High Biofilm-Specific Tolerance to the Fluoroquinolone Ofloxacin

PubMed Central

Bernier, Steve P.; Lebeaux, David; DeFrancesco, Alicia S.; Valomon, Amandine; Soubigou, Guillaume; Coppée, Jean-Yves; Ghigo, Jean-Marc; Beloin, Christophe

2013-01-01

High levels of antibiotic tolerance are a hallmark of bacterial biofilms. In contrast to well-characterized inherited antibiotic resistance, molecular mechanisms leading to reversible and transient antibiotic tolerance displayed by biofilm bacteria are still poorly understood. The physiological heterogeneity of biofilms influences the formation of transient specialized subpopulations that may be more tolerant to antibiotics. In this study, we used random transposon mutagenesis to identify biofilm-specific tolerant mutants normally exhibited by subpopulations located in specialized niches of heterogeneous biofilms. Using Escherichia coli as a model organism, we demonstrated, through identification of amino acid auxotroph mutants, that starved biofilms exhibited significantly greater tolerance towards fluoroquinolone ofloxacin than their planktonic counterparts. We demonstrated that the biofilm-associated tolerance to ofloxacin was fully dependent on a functional SOS response upon starvation to both amino acids and carbon source and partially dependent on the stringent response upon leucine starvation. However, the biofilm-specific ofloxacin increased tolerance did not involve any of the SOS-induced toxin–antitoxin systems previously associated with formation of highly tolerant persisters. We further demonstrated that ofloxacin tolerance was induced as a function of biofilm age, which was dependent on the SOS response. Our results therefore show that the SOS stress response induced in heterogeneous and nutrient-deprived biofilm microenvironments is a molecular mechanism leading to biofilm-specific high tolerance to the fluoroquinolone ofloxacin. PMID:23300476

Protein Kinase A Regulates Constitutive Expression of Small Heat-Shock Genes in an Msn2/4p-Independent and Hsf1p-Dependent Manner in Saccharomyces cerevisiae

PubMed Central

Ferguson, Scott B.; Anderson, Erik S.; Harshaw, Robyn B.; Thate, Tim; Craig, Nancy L.; Nelson, Hillary C. M.

2005-01-01

Hsf1p, the heat-shock transcription factor from Saccharomyces cerevisiae, has a low level of constitutive transcriptional activity and is kept in this state through negative regulation. In an effort to understand this negative regulation, we developed a novel genetic selection that detects altered expression from the HSP26 promoter. Using this reporter strain, we identified mutations and dosage compensators in the Ras/cAMP signaling pathway that decrease cAMP levels and increase expression from the HSP26 promoter. In yeast, low cAMP levels reduce the catalytic activity of the cAMP-dependent kinase PKA. Previous studies had proposed that the stress response transcription factors Msn2p/4p, but not Hsf1p, are repressed by PKA. However, we found that reduction or elimination of PKA activity strongly derepresses transcription of the small heat-shock genes HSP26 and HSP12, even in the absence of MSN2/4. In a strain deleted for MSN2/4 and the PKA catalytic subunits, expression of HSP12 and HSP26 depends on HSF1 expression. Our findings indicate that Hsf1p functions downstream of PKA and suggest that PKA might be involved in negative regulation of Hsf1p activity. These results represent a major change in our understanding of how PKA signaling influences the heat-shock response and heat-shock protein expression. PMID:15545649

Climate Sensitivity, Sea Level, and Atmospheric Carbon Dioxide

NASA Technical Reports Server (NTRS)

Hansen, James; Sato, Makiko; Russell, Gary; Kharecha, Pushker

2013-01-01

Cenozoic temperature, sea level and CO2 covariations provide insights into climate sensitivity to external forcings and sea-level sensitivity to climate change. Climate sensitivity depends on the initial climate state, but potentially can be accurately inferred from precise palaeoclimate data. Pleistocene climate oscillations yield a fast-feedback climate sensitivity of 3+/-1deg C for a 4 W/sq m CO2 forcing if Holocene warming relative to the Last Glacial Maximum (LGM) is used as calibration, but the error (uncertainty) is substantial and partly subjective because of poorly defined LGM global temperature and possible human influences in the Holocene. Glacial-to-interglacial climate change leading to the prior (Eemian) interglacial is less ambiguous and implies a sensitivity in the upper part of the above range, i.e. 3-4deg C for a 4 W/sq m CO2 forcing. Slow feedbacks, especially change of ice sheet size and atmospheric CO2, amplify the total Earth system sensitivity by an amount that depends on the time scale considered. Ice sheet response time is poorly defined, but we show that the slow response and hysteresis in prevailing ice sheet models are exaggerated. We use a global model, simplified to essential processes, to investigate state dependence of climate sensitivity, finding an increased sensitivity towards warmer climates, as low cloud cover is diminished and increased water vapour elevates the tropopause. Burning all fossil fuels, we conclude, would make most of the planet uninhabitable by humans, thus calling into question strategies that emphasize adaptation to climate change.

Detuning dependence of Rabi oscillations in an InAs self-assembled quantum dot ensemble

NASA Astrophysics Data System (ADS)

Suzuki, Takeshi; Singh, Rohan; Bayer, Manfred; Ludzwig, Arne; Wieck, Andreas D.; Cundiff, Steven T.

2018-04-01

We study the coherent evolution of an InAs self-assembled quantum dot (QD) ensemble in the ultrafast regime. The evolution of the entire frequency distribution is revealed by performing prepulse two-dimensional (2D) coherent spectroscopy. Charged and neutral QDs display distinct nonlinear responses arising from two-level trion and four-level exciton-biexciton systems, respectively, and each signal is clearly separated in 2D spectra. Whereas the signals for charged QDs are symmetric with respect to the detuning, those for neutral QDs are asymmetric due to the asymmetric four-level energy structure. Experimental results for charged and neutral QDs are well reproduced by solving the optical Bloch equations, including detuning and excitation-induced dephasing (EID) effects. The temperature dependence suggests that wetting-layer carriers play an important role in EID.

Level of dependency: a simple marker associated with mortality during the 2003 heatwave among French dependent elderly people living in the community or in institutions.

PubMed

Belmin, Joël; Auffray, Jean-Christian; Berbezier, Christine; Boirin, Pascal; Mercier, Sophie; de Reviers, Béatrice; Golmard, Jean-Louis

2007-05-01

In France, the August 2003 heat wave was responsible for considerable excess mortality among the elderly. We wonder whether the dependency level could be a marker of the risk for mortality during this heat wave. Retrospective cohort study of deaths that occurred between 1 and 20 August 2003, conducted in five departments in the Paris area (Ile-de-France) among the beneficiaries of the Allocation personnalisée d'autonomie (APA), a stipend specifically allocated to dependent subjects > or =60 years of age. Their dependency level was determined by the GIR group (defined by the French law) used to fix the APA amount. Subjects' GIR group classification and demographic variables were obtained from departmental administrative files. Among the 31,603 APA beneficiaries alive on 31 July 2003, 16,779 were community dwellers and 14,824 lived in institutions. Between 1 and 20 August 2003, 858 subjects died: 300 community dwellers and 558 institutionalised (mortality rates of 2.7, 1.8 and 3.8 per cent, respectively). Independent risk factors for mortality were: age, sex and GIR group in community dwellers; age, GIR group and living in a region highly exposed to heatwave mortality for institutionalised elderly; independent factors for mortality were age, sex, GIR group, type of residence (institution/community), living in a region highly exposed to heatwave mortality and income for the overall population. The dependency level was associated with mortality during the 2003 heatwave in France, especially for elderly community dwellers. Dependency might help identify high-risk subjects and guide targeted prevention measures against heatwave-associated mortality.

Activation Dependence of Stretch Activation in Mouse Skinned Myocardium: Implications for Ventricular Function

PubMed Central

Stelzer, Julian E.; Larsson, Lars; Fitzsimons, Daniel P.; Moss, Richard L.

2006-01-01

Recent evidence suggests that ventricular ejection is partly powered by a delayed development of force, i.e., stretch activation, in regions of the ventricular wall due to stretch resulting from torsional twist of the ventricle around the apex-to-base axis. Given the potential importance of stretch activation in cardiac function, we characterized the stretch activation response and its Ca2+ dependence in murine skinned myocardium at 22°C in solutions of varying Ca2+ concentrations. Stretch activation was induced by suddenly imposing a stretch of 0.5–2.5% of initial length to the isometrically contracting muscle and then holding the muscle at the new length. The force response to stretch was multiphasic: force initially increased in proportion to the amount of stretch, reached a peak, and then declined to a minimum before redeveloping to a new steady level. This last phase of the response is the delayed force characteristic of myocardial stretch activation and is presumably due to increased attachment of cross-bridges as a consequence of stretch. The amplitude and rate of stretch activation varied with Ca2+ concentration and more specifically with the level of isometric force prior to the stretch. Since myocardial force is regulated both by Ca2+ binding to troponin-C and cross-bridge binding to thin filaments, we explored the role of cross-bridge binding in the stretch activation response using NEM-S1, a strong-binding, non-force–generating derivative of myosin subfragment 1. NEM-S1 treatment at submaximal Ca2+-activated isometric forces significantly accelerated the rate of the stretch activation response and reduced its amplitude. These data show that the rate and amplitude of myocardial stretch activation vary with the level of activation and that stretch activation involves cooperative binding of cross-bridges to the thin filament. Such a mechanism would contribute to increased systolic ejection in response to increased delivery of activator Ca2+ during excitation–contraction coupling. PMID:16446502

Marketing: A Definition for Community Colleges.

ERIC Educational Resources Information Center

Kotler, Philip; Goldgehn, Leslie A.

1981-01-01

Defines marketing and discusses the eight steps of the marketing process. Emphasizes the necessity of having one individual or committee responsible for coordinating marketing functions. Notes that marketing's success depends on its acceptance by all levels of the institution. Lists the benefits of implementing marketing in a community college.…

Two-Component Elements Mediate Interactions between Cytokinin and Salicylic Acid in Plant Immunity

PubMed Central

Argueso, Cristiana T.; Ferreira, Fernando J.; Epple, Petra; To, Jennifer P. C.; Hutchison, Claire E.; Schaller, G. Eric; Dangl, Jeffery L.; Kieber, Joseph J.

2012-01-01

Recent studies have revealed an important role for hormones in plant immunity. We are now beginning to understand the contribution of crosstalk among different hormone signaling networks to the outcome of plant–pathogen interactions. Cytokinins are plant hormones that regulate development and responses to the environment. Cytokinin signaling involves a phosphorelay circuitry similar to two-component systems used by bacteria and fungi to perceive and react to various environmental stimuli. In this study, we asked whether cytokinin and components of cytokinin signaling contribute to plant immunity. We demonstrate that cytokinin levels in Arabidopsis are important in determining the amplitude of immune responses, ultimately influencing the outcome of plant–pathogen interactions. We show that high concentrations of cytokinin lead to increased defense responses to a virulent oomycete pathogen, through a process that is dependent on salicylic acid (SA) accumulation and activation of defense gene expression. Surprisingly, treatment with lower concentrations of cytokinin results in increased susceptibility. These functions for cytokinin in plant immunity require a host phosphorelay system and are mediated in part by type-A response regulators, which act as negative regulators of basal and pathogen-induced SA–dependent gene expression. Our results support a model in which cytokinin up-regulates plant immunity via an elevation of SA–dependent defense responses and in which SA in turn feedback-inhibits cytokinin signaling. The crosstalk between cytokinin and SA signaling networks may help plants fine-tune defense responses against pathogens. PMID:22291601

Dynamics of the Murine Humoral Immune Response to Neisseria meningitidis Group B Capsular Polysaccharide

PubMed Central

Colino, Jesús; Outschoorn, Ingrid

1998-01-01

Immunization with Neisseria meningitidis group B capsular polysaccharide (CpsB) elicited responses in adult mice that showed the typical dynamic characteristics of the response to a thymus-independent antigen, in contrast to the thymus-dependent behavior of antibody responses to CpsC. The former had a short latent period and showed a rapid increase in serum antibodies that peaked at day 5, and immunoglobulin M (IgM) was the major isotype even though IgG (mainly IgG2a and IgG2b) was also detectable. This response was of short duration, and the specific antibodies were rapidly cleared from the circulation. The secondary responses were similar in magnitude, kinetics, IgM predominance, and IgG distribution. Nevertheless, a threefold IgG increase, a correlation between IgM and IgG levels, and dose-dependent secondary responses were observed. Hyperimmunization considerably reinforced these responses: 10-fold for IgM and 300-fold for IgG. This favored isotype switch was accompanied by a progressive change in the subclass distribution to IgG3 (62%) and IgG1 (28%), along with the possible generation of B-cell memory. The results indicate that CpsB is being strictly thymus independent and suggest that unresponsiveness to purified CpsB is due to tolerance. PMID:9453603

Dynamics of the murine humoral immune response to Neisseria meningitis group B capsular polysaccharide.

PubMed

Colino, J; Outschoorn, I

1998-02-01

Immunization with Neisseria meningitidis group B capsular polysaccharide (CpsB) elicited responses in adult mice that showed the typical dynamic characteristics of the response to a thymus-independent antigen, in contrast to the thymus-dependent behavior of antibody responses to CpsC. The former had a short latent period and showed a rapid increase in serum antibodies that peaked at day 5, and immunoglobulin M (IgM) was the major isotype even though IgG (mainly IgG2a and IgG2b) was also detectable. This response was of short duration, and the specific antibodies were rapidly cleared from the circulation. The secondary responses were similar in magnitude, kinetics, IgM predominance, and IgG distribution. Nevertheless, a threefold IgG increase, a correlation between IgM and IgG levels, and dose-dependent secondary responses were observed. Hyperimmunization considerably reinforced these responses: 10-fold for IgM and 300-fold for IgG. This favored isotype switch was accompanied by a progressive change in the subclass distribution to IgG3 (62%) and IgG1 (28%), along with the possible generation of B-cell memory. The results indicate that CpsB is being strictly thymus independent and suggest that unresponsiveness to purified CpsB is due to tolerance.

Tunnel magnetoresistance and linear conductance of double quantum dots strongly coupled to ferromagnetic leads

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

Weymann, Ireneusz, E-mail: weymann@amu.edu.pl

2015-05-07

We analyze the spin-dependent linear-response transport properties of double quantum dots strongly coupled to external ferromagnetic leads. By using the numerical renormalization group method, we determine the dependence of the linear conductance and tunnel magnetoresistance on the degree of spin polarization of the leads and the position of the double dot levels. We focus on the transport regime where the system exhibits the SU(4) Kondo effect. It is shown that the presence of ferromagnets generally leads the suppression of the linear conductance due to the presence of an exchange field. Moreover, the exchange field gives rise to a transition frommore » the SU(4) to the orbital SU(2) Kondo effect. We also analyze the dependence of the tunnel magnetoresistance on the double dot levels' positions and show that it exhibits a very nontrivial behavior.« less

Morris Water Maze Training in Mice Elevates Hippocampal Levels of Transcription Factors Nuclear Factor (Erythroid-derived 2)-like 2 and Nuclear Factor Kappa B p65

PubMed Central

Snow, Wanda M.; Pahlavan, Payam S.; Djordjevic, Jelena; McAllister, Danielle; Platt, Eric E.; Alashmali, Shoug; Bernstein, Michael J.; Suh, Miyoung; Albensi, Benedict C.

2015-01-01

Research has identified several transcription factors that regulate activity-dependent plasticity and memory, with cAMP-response element binding protein (CREB) being the most well-studied. In neurons, CREB activation is influenced by the transcription factor nuclear factor kappa B (NF-κB), considered central to immunity but more recently implicated in memory. The transcription factor early growth response-2 (Egr-2), an NF-κB gene target, is also associated with learning and memory. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an antioxidant transcription factor linked to NF-κB in pathological conditions, has not been studied in normal memory. Given that numerous transcription factors implicated in activity-dependent plasticity demonstrate connections to NF-κB, this study simultaneously evaluated protein levels of NF-κB, CREB, Egr-2, Nrf2, and actin in hippocampi from young (1 month-old) weanling CD1 mice after training in the Morris water maze, a hippocampal-dependent spatial memory task. After a 6-day acquisition period, time to locate the hidden platform decreased in the Morris water maze. Mice spent more time in the target vs. non-target quadrants of the maze, suggestive of recall of the platform location. Western blot data revealed a decrease in NF-κB p50 protein after training relative to controls, whereas NF-κB p65, Nrf2 and actin increased. Nrf2 levels were correlated with platform crosses in nearly all tested animals. These data demonstrate that training in a spatial memory task results in alterations in and associations with particular transcription factors in the hippocampus, including upregulation of NF-κB p65 and Nrf2. Training-induced increases in actin protein levels caution against its use as a loading control in immunoblot studies examining activity-dependent plasticity, learning, and memory. PMID:26635523

Temporal response of hydraulic head, temperature, and chloride concentrations to sea-level changes, Floridan aquifer system, USA

USGS Publications Warehouse

Hughes, J.D.; Vacher, H. Leonard; Sanford, W.E.

2009-01-01

Three-dimensional density-dependent flow and transport modeling of the Floridan aquifer system, USA shows that current chloride concentrations are not in equilibrium with current sea level and, second, that the geometric configuration of the aquifer has a significant effect on system responses. The modeling shows that hydraulic head equilibrates first, followed by temperatures, and then by chloride concentrations. The model was constructed using a modified version of SUTRA capable of simulating multi-species heat and solute transport, and was compared to pre-development conditions using hydraulic heads, chloride concentrations, and temperatures from 315 observation wells. Three hypothetical, sinusoidal sea-level changes occurring over 100,000 years were used to evaluate how the simulated aquifer responds to sea-level changes. Model results show that hydraulic head responses lag behind sea-level changes only where the Miocene Hawthorn confining unit is thick and represents a significant restriction to flow. Temperatures equilibrate quickly except where the Hawthorn confining unit is thick and the duration of the sea-level event is long (exceeding 30,000 years). Response times for chloride concentrations to equilibrate are shortest near the coastline and where the aquifer is unconfined; in contrast, chloride concentrations do not change significantly over the 100,000-year simulation period where the Hawthorn confining unit is thick. ?? US Government 2008.

Dynamic endocrine responses to stress: evidence for energetic constraints and status dependence in breeding male green turtles.

PubMed

Jessop, Tim S; Knapp, Rosemary; Whittier, Joan M; Limpus, Col J

2002-03-01

During reproduction, male vertebrates may exhibit a continuum of interactions between sex and adrenal steroids during stressful events, the outcome of which may be important in either reducing or promoting male reproductive success. We studied adult male green turtles (Chelonia mydas) to examine if they altered plasma corticosterone (CORT) and androgen levels in response to a standardized capture/restraint stressor as potential mechanisms to maintain reproductive activity during stressful events. At the population level, we found that migrant breeding males had a significantly smaller CORT response to the capture/restraint stressor compared to nonbreeding males and that this decreased response coincided with the generally poorer body condition of migrant breeders. In contrast, plasma androgen levels decreased significantly in response to the capture/restraint stressor in migrant breeding males, but not in nonbreeding and pre-migrant breeding males. For individual migrant breeding males, the magnitude of their CORT and androgen responses to the capture/restraint stressor was highly correlated with their body condition and body length, respectively. Our results demonstrate that male green turtles exhibit complex interactions in their endocrine responses to a capture/restraint stressor and that variation in these interactions is associated with differences in males' reproductive, energetic, and physical state. We hypothesize that interplay between physical status and plasma hormone responses to stressors could have important consequences for male green turtle reproduction.

Pheromone responsiveness threshold depends on temporal integration by antennal lobe projection neurons

PubMed Central

Tabuchi, Masashi; Sakurai, Takeshi; Mitsuno, Hidefumi; Namiki, Shigehiro; Minegishi, Ryo; Shiotsuki, Takahiro; Uchino, Keiro; Sezutsu, Hideki; Tamura, Toshiki; Haupt, Stephan Shuichi; Nakatani, Kei; Kanzaki, Ryohei

2013-01-01

The olfactory system of male moths has an extreme sensitivity with the capability to detect and recognize conspecific pheromones dispersed and greatly diluted in the air. Just 170 molecules of the silkmoth (Bombyx mori) sex pheromone bombykol are sufficient to induce sexual behavior in the male. However, it is still unclear how the sensitivity of olfactory receptor neurons (ORNs) is relayed through the brain to generate high behavioral responsiveness. Here, we show that ORN activity that is subthreshold in terms of behavior can be amplified to suprathreshold levels by temporal integration in antennal lobe projection neurons (PNs) if occurring within a specific time window. To control ORN inputs with high temporal resolution, channelrhodopsin-2 was genetically introduced into bombykol-responsive ORNs. Temporal integration in PNs was only observed for weak inputs, but not for strong inputs. Pharmacological dissection revealed that GABAergic mechanisms inhibit temporal integration of strong inputs, showing that GABA signaling regulates PN responses in a stimulus-dependent fashion. Our results show that boosting of the PNs’ responses by temporal integration of olfactory information occurs specifically near the behavioral threshold, effectively defining the lower bound for behavioral responsiveness. PMID:24006366

Benzo(a)pyrene-induced cytochrome p4501A expression of four freshwater fishes (Oryzias latipes, Danio rerio, Cyprinus carpio, and Zacco platypus).

PubMed

Lee, Jin Wuk; Yoon, Hong-Gil; Lee, Sung Kyu

2015-05-01

Oryzias latipes, Danio rerio, Cyprinus carpio, and Zacco platypus are useful indicator species for CYP1A biomarker studies; however, comparative studies have not been performed. To compare susceptibility, dose- and time-dependent CYP1A induction at the mRNA and protein levels in response to benzo(a)pyrene (BaP) exposure was analyzed. At the mRNA level, a statistically significant difference was found among the four species; however, such was not observed at the protein level. C. carpio showed the highest CYP1A induction level and the steepest slope in the dose-response curve. To assess susceptibility, the difference in CYP1A mRNA induction among species must be considered, and C. carpio was the most sensitive species of the four evaluated in terms of CYP1A expression. Copyright © 2015 Elsevier B.V. All rights reserved.

Chromosome 15q25.1 genetic markers associated with level of response to alcohol in humans.

PubMed

Joslyn, Geoff; Brush, Gerry; Robertson, Margaret; Smith, Tom L; Kalmijn, Jelger; Schuckit, Marc; White, Raymond L

2008-12-23

As with other genetically complex common psychiatric and medical conditions, multiple genetic and environmental components contribute to alcohol use disorders (AUDs), which can confound attempts to identify genetic components. Intermediate phenotypes are often more closely correlated with underlying biology and have often proven invaluable in genetic studies. Level of response (LR) to alcohol is an intermediate phenotype for AUDs, and individuals with a low LR are at increased risk. A high rate of concurrent alcohol and nicotine use and dependence suggests that these conditions may share biochemical and genetic mechanisms. Genetic association studies indicate that a genetic locus, which includes the CHRNA5-CHRNA3-CHRNB4 gene cluster, plays a role in nicotine consumption and dependence. Genetic association with alcohol dependence was also recently shown. We show here that two of the markers from the nicotine studies also show an association (multiple testing corrected P < 0.025) with several LR phenotypes in a sample of 367 siblings. Additional markers in the region were analyzed and shown to be located in a 250-kb expanse of high linkage disequilibrium containing three additional genes. These findings indicate that LR intermediate phenotypes have utility in genetic approaches to AUDs and will prove valuable in the identification of other genetic loci conferring susceptibility to AUDs.

RU486 did not exacerbate cytokine release in mice challenged with LPS nor in db/db mice

PubMed Central

Yang, Baichun; Trump, Ryan P; Shen, Ying; McNulty, Judi A; Clifton, Lisa G; Stimpson, Stephen A; Lin, Peiyuan; Pahel, Greg L

2008-01-01

Background Glucocorticoids down-regulate cytokine synthesis and suppress inflammatory responses. The glucocorticoid receptor (GR) antagonist RU486 may exacerbate the inflammatory response, and concerns over this exacerbation have limited the development and clinical use of GR antagonists in the treatment of diabetes and depression. We investigated the effects of RU486 on serum cytokines in db/db mice and on lipopolysaccharide (LPS)-induced circulating TNFα levels in both normal AKR mice and diet-induced obese (DIO) C57BL/6 mice. Results Chronic treatment of db/db mice with RU486 dose-dependently decreased blood glucose, increased serum corticosterone and ACTH, but did not affect serum MCP-1 and IL-6 levels. LPS dose-dependently increased serum TNFα in both AKR and C57BL/6 DIO mice, along with increased circulating corticosterone and ACTH. Pretreatment of the mice with RU486 dose-dependently suppressed the LPS induced increases in serum TNFα and further increased serum corticosterone. Conclusion RU486 at doses that were efficacious in lowering blood glucose did not exacerbate cytokine release in these three mouse models. RU486 actually suppressed the lower dose LPS-mediated TNFα release, possibly due to the increased release of glucocorticoids. PMID:18474108

Cellular cholesterol regulates ubiquitination and degradation of the cholesterol export proteins ABCA1 and ABCG1.

PubMed

Hsieh, Victar; Kim, Mi-Jurng; Gelissen, Ingrid C; Brown, Andrew J; Sandoval, Cecilia; Hallab, Jeannette C; Kockx, Maaike; Traini, Mathew; Jessup, Wendy; Kritharides, Leonard

2014-03-14

The objective of this study was to examine the influence of cholesterol in post-translational control of ABCA1 and ABCG1 protein expression. Using CHO cell lines stably expressing human ABCA1 or ABCG1, we observed that the abundance of these proteins is increased by cell cholesterol loading. The response to increased cholesterol is rapid, is independent of transcription, and appears to be specific for these membrane proteins. The effect is mediated through cholesterol-dependent inhibition of transporter protein degradation. Cell cholesterol loading similarly regulates degradation of endogenously expressed ABCA1 and ABCG1 in human THP-1 macrophages. Turnover of ABCA1 and ABCG1 is strongly inhibited by proteasomal inhibitors and is unresponsive to inhibitors of lysosomal proteolysis. Furthermore, cell cholesterol loading inhibits ubiquitination of ABCA1 and ABCG1. Our findings provide evidence for a rapid, cholesterol-dependent, post-translational control of ABCA1 and ABCG1 protein levels, mediated through a specific and sterol-sensitive mechanism for suppression of transporter protein ubiquitination, which in turn decreases proteasomal degradation. This provides a mechanism for acute fine-tuning of cholesterol transporter activity in response to fluctuations in cell cholesterol levels, in addition to the longer term cholesterol-dependent transcriptional regulation of these genes.

Cellular Cholesterol Regulates Ubiquitination and Degradation of the Cholesterol Export Proteins ABCA1 and ABCG1*

PubMed Central

Hsieh, Victar; Kim, Mi-Jurng; Gelissen, Ingrid C.; Brown, Andrew J.; Sandoval, Cecilia; Hallab, Jeannette C.; Kockx, Maaike; Traini, Mathew; Jessup, Wendy; Kritharides, Leonard

2014-01-01

The objective of this study was to examine the influence of cholesterol in post-translational control of ABCA1 and ABCG1 protein expression. Using CHO cell lines stably expressing human ABCA1 or ABCG1, we observed that the abundance of these proteins is increased by cell cholesterol loading. The response to increased cholesterol is rapid, is independent of transcription, and appears to be specific for these membrane proteins. The effect is mediated through cholesterol-dependent inhibition of transporter protein degradation. Cell cholesterol loading similarly regulates degradation of endogenously expressed ABCA1 and ABCG1 in human THP-1 macrophages. Turnover of ABCA1 and ABCG1 is strongly inhibited by proteasomal inhibitors and is unresponsive to inhibitors of lysosomal proteolysis. Furthermore, cell cholesterol loading inhibits ubiquitination of ABCA1 and ABCG1. Our findings provide evidence for a rapid, cholesterol-dependent, post-translational control of ABCA1 and ABCG1 protein levels, mediated through a specific and sterol-sensitive mechanism for suppression of transporter protein ubiquitination, which in turn decreases proteasomal degradation. This provides a mechanism for acute fine-tuning of cholesterol transporter activity in response to fluctuations in cell cholesterol levels, in addition to the longer term cholesterol-dependent transcriptional regulation of these genes. PMID:24500716

The c-Abl signaling network in the radioadaptive response

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

Chi-Min, Yuan

2014-01-28

The radioadaptive response, or radiation hormesis, i.e. a low dose of radiation can protect cells and organisms from the effects of a subsequent higher dose, is a widely recognized phenomenon. Mechanisms underlying such radiation hormesis, however, remain largely unclear. Preliminary studies indicate an important role of c-Abl signaling in mediating the radioadaptive response. We propose to investigate how c-Abl regulates the crosstalk between p53 and NFκB in response to low doses irradiation. We found in our recent study that low dose IR induces a reciprocal p53 suppression and NFκB activation, which induces HIF-a and subsequently a metabolic reprogramming resulting inmore » a transition from oxidative phosphorylation to glycolysis. Of importance is that this glycolytic switch is essential for the radioadaptive response. This low-dose radiationinduced HIF1α activation was in sharp contrast with the high-dose IR-induced p53 activation and HIF1α inhibition. HIF1α and p53 seem to play distinct roles in mediating the radiation dose-dependent metabolic response. The induction of HIF1α-mediated glycolysis is restricted to a low dose range of radiation, which may have important implications in assessing the level of radiation exposure and its potential health risk. Our results support a dose-dependent metabolic response to IR. When IR doses are below the threshold of causing detectable DNA damage (<0.2Gy) and thus little p53 activation, HIF1α is induced resulting in induction of glycolysis and increased radiation resistance. When the radiation dose reaches levels eliciting DNA damage, p53 is activated and diminishes the activity of HIF1α and glycolysis, leading to the induction of cell death. Our work challenges the LNT model of radiation exposure risk and provides a metabolic mechanism of radioadaptive response. The study supports a need for determining the p53 and HIF1α activity as a potential reliable biological readout of radiation exposure in humans. The exquisite sensitivity of cellular metabolism to low doses of radiation could also serve as a valuable biomarker for estimating the health effects of low-level radiation exposure.« less

Progesterone modulation of alpha5 nAChR subunits influences anxiety-related behavior during estrus cycle.

PubMed

Gangitano, D; Salas, R; Teng, Y; Perez, E; De Biasi, M

2009-06-01

Smokers often report an anxiolytic effect of cigarettes. In addition, stress-related disorders such as anxiety, post-traumatic stress syndrome and depression are often associated with chronic nicotine use. To study the role of the alpha5 nicotinic acetylcholine receptor subunit in anxiety-related responses, control and alpha5 subunit null mice (alpha5(-/-)) were subjected to the open field activity (OFA), light-dark box (LDB) and elevated plus maze (EPM) tests. In the OFA and LDB, alpha5(-/-) behaved like wild-type controls. In the EPM, female alpha5(-/-) mice displayed an anxiolytic-like phenotype, while male alpha5(-/-) mice were undistinguishable from littermate controls. We studied the hypothalamus-pituitary-adrenal axis by measuring plasma corticosterone and hypothalamic corticotropin-releasing factor. Consistent with an anxiolytic-like phenotype, female alpha5(-/-) mice displayed lower basal corticosterone levels. To test whether gonadal steroids regulate the expression of alpha5, we treated cultured NTera 2 cells with progesterone and found that alpha5 protein levels were upregulated. In addition, brain levels of alpha5 mRNA increased upon progesterone injection into ovariectomized wild-type females. Finally, we tested anxiety levels in the EPM during the estrous cycle. The estrus phase (when progesterone levels are low) is anxiolytic-like in wild-type mice, but no cycle-dependent fluctuations in anxiety levels were found in alpha5(-/-) females. Thus, alpha5-containing neuronal nicotinic acetylcholine receptors may be mediators of anxiogenic responses, and progesterone-dependent modulation of alpha5 expression may contribute to fluctuations in anxiety levels during the ovarian cycle.

Responses of woody species to spatial and temporal ground water changes in coastal sand dune systems

NASA Astrophysics Data System (ADS)

Máguas, C.; Rascher, K. G.; Martins-Loução, A.; Carvalho, P.; Pinho, P.; Ramos, M.; Correia, O.; Werner, C.

2011-12-01

In spite of the relative importance of groundwater in costal dune systems, studies concerning the responses of vegetation to ground water (GW) availability variations, particularly in Mediterranean regions, are scarce. Thus, the main purpose of this study is to compare the responses of co-occurring species possessing different functional traits, to changes in GW levels (i.e. the lowering of GW levels) in a sand dune ecosystem. For that, five sites were established within a 1 km2 area in a meso-mediterranean sand dune ecosystem dominated by a Pinus pinaster forest. Due to natural topographic variability and anthropogenic GW exploitation, substantial variability in depth to GW between sites was found. Under these conditions it was possible to identify the degree of usage and dependence on GW of different plant species (two deep-rooted trees, a drought adapted shrub, a phreatophyte and a non-native woody invader) and how GW dependence varied seasonally and between the heterogeneous sites. Results indicated that the plant species had differential responses to changes in GW depth according to specific functional traits (i.e. rooting depth, leaf morphology, and water use strategy). Species comparison revealed that variability in pre-dawn water potential (Ψpre) and bulk leaf δ13C was related to site differences in GW use in the deep-rooted (Pinus pinaster, Myrica faya) and phreatophyte (Salix repens) species. However, such variation was more evident during spring than during summer drought. The exotic invader, Acacia longifolia, which does not possess a very deep root system, presented the largest seasonal variability in Ψpre and bulk leaf δ13C. In contrast, the response of Corema album, an endemic understory drought-adapted shrub, seemed to be independent of water availability across seasons and sites. Thus, the susceptibility to lowering of GW due to anthropogenic exploitation, in plant species from sand dunes, is variable, being particularly relevant for deep rooted species and phreatophytes, which seem to depend heavily on access to GW.

Identification of conserved cis-elements and transcription factors required for sterol-regulated transcription of stearoyl-CoA desaturase 1 and 2.

PubMed

Tabor, D E; Kim, J B; Spiegelman, B M; Edwards, P A

1999-07-16

We previously identified stearoyl-CoA desaturase 2 (SCD2) as a new member of the family of genes that are transcriptionally regulated in response to changing levels of nuclear sterol regulatory element binding proteins (SREBPs) or adipocyte determination and differentiation factor 1 (ADD1). A novel sterol regulatory element (SRE) (5'-AGCAGATTGTG-3') identified in the proximal promoter of the mouse SCD2 gene is required for induction of SCD2 promoter-reporter genes in response to cellular sterol depletion (Tabor, D. E., Kim, J. B., Spiegelman, B. M., and Edwards, P. A. (1998) J. Biol. Chem. 273, 22052-22058). In this report, we demonstrate that this novel SRE is both present in the promoter of the SCD1 gene and is critical for the sterol-dependent transcription of SCD1 promoter-reporter genes. Two conserved cis elements (5'-CCAAT-3') lie 5 and 48 base pairs 3' of the novel SREs in the promoters of both the SCD1 and SCD2 murine genes. Mutation of either of these putative NF-Y binding sites attenuates the transcriptional activation of SCD1 or SCD2 promoter-reporter genes in response to cellular sterol deprivation. Induction of both reporter genes is also attenuated when cells are cotransfected with dominant-negative forms of either NF-Y or SREBP. In addition, we demonstrate that the induction of SCD1 and SCD2 mRNAs that occurs during the differentiation of 3T3-L1 preadipocytes to adipocytes is paralleled by an increase in the levels of ADD1/SREBP-1c and that the SCD1 and SCD2 mRNAs are induced to even higher levels in response to ectopic expression of ADD1/SREBP-1c. We conclude that transcription of both SCD1 and SCD2 genes is responsive to cellular sterol levels and to the levels of nuclear SREBP/ADD1 and that transcriptional induction requires three spatially conserved cis elements, that bind SREBP and NF-Y. Additional studies demonstrate that maximal transcriptional repression of SCD2 reporter genes in response to an exogenous polyunsaturated fatty acid is dependent upon the SRE and the adjacent CCAAT motif.

Helminth Infections Coincident with Active Pulmonary Tuberculosis Inhibit Mono- and Multifunctional CD4+ and CD8+ T Cell Responses in a Process Dependent on IL-10

PubMed Central

George, Parakkal Jovvian; Anuradha, Rajamanickam; Kumar, Nathella Pavan; Sridhar, Rathinam; Banurekha, Vaithilingam V.; Nutman, Thomas B.; Babu, Subash

2014-01-01

Tissue invasive helminth infections and tuberculosis (TB) are co-endemic in many parts of the world and can trigger immune responses that might antagonize each other. We have previously shown that helminth infections modulate the Th1 and Th17 responses to mycobacterial-antigens in latent TB. To determine whether helminth infections modulate antigen-specific and non-specific immune responses in active pulmonary TB, we examined CD4+ and CD8+ T cell responses as well as the systemic (plasma) cytokine levels in individuals with pulmonary TB with or without two distinct helminth infections—Wuchereria bancrofti and Strongyloides stercoralis infection. By analyzing the frequencies of Th1 and Th17 CD4+ and CD8+ T cells and their component subsets (including multifunctional cells), we report a significant diminution in the mycobacterial–specific frequencies of mono- and multi–functional CD4+ Th1 and (to a lesser extent) Th17 cells when concomitant filarial or Strongyloides infection occurs. The impairment in CD4+ and CD8+ T cell cytokine responses was antigen-specific as polyclonal activated T cell frequencies were equivalent irrespective of helminth infection status. This diminution in T cell responses was also reflected in diminished circulating levels of Th1 (IFN-γ, TNF-α and IL-2)- and Th17 (IL-17A and IL-17F)-associated cytokines. Finally, we demonstrate that for the filarial co-infections at least, this diminished frequency of multifunctional CD4+ T cell responses was partially dependent on IL-10 as IL-10 blockade significantly increased the frequencies of CD4+ Th1 cells. Thus, co-existent helminth infection is associated with an IL-10 mediated (for filarial infection) profound inhibition of antigen-specific CD4+ T cell responses as well as protective systemic cytokine responses in active pulmonary TB. PMID:25211342

Robust Measurement via A Fused Latent and Graphical Item Response Theory Model.

PubMed

Chen, Yunxiao; Li, Xiaoou; Liu, Jingchen; Ying, Zhiliang

2018-03-12

Item response theory (IRT) plays an important role in psychological and educational measurement. Unlike the classical testing theory, IRT models aggregate the item level information, yielding more accurate measurements. Most IRT models assume local independence, an assumption not likely to be satisfied in practice, especially when the number of items is large. Results in the literature and simulation studies in this paper reveal that misspecifying the local independence assumption may result in inaccurate measurements and differential item functioning. To provide more robust measurements, we propose an integrated approach by adding a graphical component to a multidimensional IRT model that can offset the effect of unknown local dependence. The new model contains a confirmatory latent variable component, which measures the targeted latent traits, and a graphical component, which captures the local dependence. An efficient proximal algorithm is proposed for the parameter estimation and structure learning of the local dependence. This approach can substantially improve the measurement, given no prior information on the local dependence structure. The model can be applied to measure both a unidimensional latent trait and multidimensional latent traits.

Electric Field-Dependent Photoluminescence in Multilayer Transition Metal Dichalcogenides

NASA Astrophysics Data System (ADS)

Stanev, T. K.; Henning, A.; Sangwan, V. K.; Speiser, N.; Stern, N. P.; Lauhon, L. J.; Hersam, M. C.; Wang, K.; Valencia, D.; Charles, J.; Kubis, T. C.

Owing to interlayer coupling, transition metal dichalcogenides (TMDCs) such as MoS2 exhibit strong layer dependence of optical and electronic phenomena such as the band gap and trion and neutral exciton population dynamics. Here, we systematically measure the effect of layer number on the optical response of multilayer MoS2 in an external electric field, observing field and layer number dependent emission energy and photoluminescence intensity. These effects are studied in few (2-6) and bulk (11 +) layered structures at low temperatures. In MoS2\\ the observed layer dependence arises from several mechanisms, including interlayer charge transfer, band structure, Stark Effect, Fermi level changes, screening, and surface effects, so it can be challenging to isolate how these mechanisms impact the observables. Because it behaves like a stack of weakly interacting monolayers rather than multilayer or bulk, ReS2 provides a comparison to traditional TMDCs to help isolate the underlying physical mechanisms dictating the response of multilayers. This work is supported by the National Science Foundation MRSEC program (DMR-1121262), and the 2-DARE Grant (EFRI-1433510). N.P.S. is an Alfred P. Sloan Research Fellow.

The Effect of Temperature Dependent Material Nonlinearities on the Response of Piezoelectric Composite Plates

NASA Technical Reports Server (NTRS)

Lee, Ho-Jun; Saravanos, Dimitris A.

1997-01-01

Previously developed analytical formulations for piezoelectric composite plates are extended to account for the nonlinear effects of temperature on material properties. The temperature dependence of the composite and piezoelectric properties are represented at the material level through the thermopiezoelectric constitutive equations. In addition to capturing thermal effects from temperature dependent material properties, this formulation also accounts for thermal effects arising from: (1) coefficient of thermal expansion mismatch between the various composite and piezoelectric plies and (2) pyroelectric effects on the piezoelectric material. The constitutive equations are incorporated into a layerwise laminate theory to provide a unified representation of the coupled mechanical, electrical, and thermal behavior of smart structures. Corresponding finite element equations are derived and implemented for a bilinear plate element with the inherent capability to model both the active and sensory response of piezoelectric composite laminates. Numerical studies are conducted on a simply supported composite plate with attached piezoceramic patches under thermal gradients to investigate the nonlinear effects of material property temperature dependence on the displacements, sensory voltages, active voltages required to minimize thermal deflections, and the resultant stress states.

Parathyroid hormone modulates the response of osteoblast-like cells to mechanical stimulation

NASA Technical Reports Server (NTRS)

Ryder, K. D.; Duncan, R. L.

2000-01-01

Mechanical loading stimulates many responses in bone and osteoblasts associated with osteogenesis. Since loading and parathyroid hormone (PTH) activate similar signaling pathways in osteoblasts, we postulate that PTH can potentiate the effects of mechanical stimulation. Using an in vitro four-point bending device, we found that expression of COX-2, the inducible isoform of cyclooxygenase, was dependent on fluid forces generated across the culture plate, but not physiologic levels of strain in MC3T3-E1 osteoblast-like cells. Addition of 50 nM PTH during loading increased COX-2 expression at both subthreshold and threshold levels of fluid forces compared with either stimuli alone. We also demonstrated that application of fluid shear to MC3T3-E1 cells induced a rapid increase in [Ca(2+)](i). Although PTH did not significantly change [Ca(2+)](i) levels, flow and PTH did produce a significantly greater [Ca(2+)](i) response and increased the number of responding cells than is found in fluid shear alone. The [Ca(2+)](i) response to these stimuli was significantly decreased when the mechanosensitive channel inhibitor, gadolinium, was present. These studies indicate that PTH increases the cellular responses of osteoblasts to mechanical loading. Furthermore, this response may be mediated by alterations in [Ca(2+)](i) by modulating the mechanosensitive channel.

Examining the Predictive Validity of a Dynamic Assessment of Decoding to Forecast Response Tier 2 to Intervention

PubMed Central

Cho, Eunsoo; Compton, Donald L.; Fuchs, Doug; Fuchs, Lynn S.; Bouton, Bobette

2013-01-01

The purpose of this study was to examine the role of a dynamic assessment (DA) of decoding in predicting responsiveness to Tier 2 small group tutoring in a response-to-intervention model. First-grade students (n=134) who did not show adequate progress in Tier 1 based on 6 weeks of progress monitoring received Tier 2 small-group tutoring in reading for 14 weeks. Student responsiveness to Tier 2 was assessed weekly with word identification fluency (WIF). A series of conditional individual growth curve analyses were completed that modeled the correlates of WIF growth (final level of performance and growth). Its purpose was to examine the predictive validity of DA in the presence of 3 sets of variables: static decoding measures, Tier 1 responsiveness indicators, and pre-reading variables (phonemic awareness, rapid letter naming, oral vocabulary, and IQ). DA was a significant predictor of final level and growth, uniquely explaining 3% – 13% of the variance in Tier 2 responsiveness depending on the competing predictors in the model and WIF outcome (final level of performance or growth). Although the additional variances explained uniquely by DA were relatively small, results indicate the potential of DA in identifying Tier 2 nonresponders. PMID:23213050

Examining the predictive validity of a dynamic assessment of decoding to forecast response to tier 2 intervention.

PubMed

Cho, Eunsoo; Compton, Donald L; Fuchs, Douglas; Fuchs, Lynn S; Bouton, Bobette

2014-01-01

The purpose of this study was to examine the role of a dynamic assessment (DA) of decoding in predicting responsiveness to Tier 2 small-group tutoring in a response-to-intervention model. First grade students (n = 134) who did not show adequate progress in Tier 1 based on 6 weeks of progress monitoring received Tier 2 small-group tutoring in reading for 14 weeks. Student responsiveness to Tier 2 was assessed weekly with word identification fluency (WIF). A series of conditional individual growth curve analyses were completed that modeled the correlates of WIF growth (final level of performance and growth). Its purpose was to examine the predictive validity of DA in the presence of three sets of variables: static decoding measures, Tier 1 responsiveness indicators, and prereading variables (phonemic awareness, rapid letter naming, oral vocabulary, and IQ). DA was a significant predictor of final level and growth, uniquely explaining 3% to 13% of the variance in Tier 2 responsiveness depending on the competing predictors in the model and WIF outcome (final level of performance or growth). Although the additional variances explained uniquely by DA were relatively small, results indicate the potential of DA in identifying Tier 2 nonresponders. © Hammill Institute on Disabilities 2012.

Defective B cell response to T-dependent immunization in lupus-prone mice

PubMed Central

Niu, Haitao; Sobel, Eric S.; Morel, Laurence

2009-01-01

Lupus anti-nuclear Abs show the characteristics of Ag-driven T cell-dependent (TD) humoral responses. If autoAgs elicit the same response as exogenous Ags, lupus should enhance humoral responses to immunization. Blunted responses to various immunizations have, however, been reported in a significant portion of lupus patients. In this study, we show that lupus-prone B6.Sle1.Sle2.Sle3 (B6.TC) mice produce significantly less Ab in response to TD immunization than congenic controls, while producing significantly more total Ig. This blunted Ab response to TD Ag could be reconstituted with B6.TC B and CD4+ T cells. Multiple defects were found in the B6.TC response to NP-KLH as compared to total Ig, including a smaller percentage of B cells participating to the NP-response, a reduced entry into germinal centers, and highly defective production of NP-specific long-lived plasma cells in the bone marrow. B6.TC plasma cells expressed reduced levels of FcγRIIb, which suggests that reduced apoptosis in resident plasma cells prevents the establishment of newly-formed NP-specific plasma cells in bone marrow niches. Overall, these results show that lupus-prone mice responded differently to auto- and exogenous antigens and suggest that low FcγRIIb, hypergammaglobulinemia and high autoantibody production would be predictive of a poor response to immunization in lupus patients. PMID:18924209