The effect of music-induced mood on attentional networks.

PubMed

Jiang, Jun; Scolaro, Ashley J; Bailey, Kira; Chen, Antao

2011-06-01

Attention network theory suggests that there are three separate neural networks that execute the discrete functions of alerting, orienting, and executive attention. Previous research on the influence of mood on attention has shown subtle and inconsistent results. The attention network theory may aid in clarifying the influence of mood on attention. The present study investigated the influence of mood on attentional networks in a normal population. Participants performed the Attention Network Test (ANT), which provides functional measures of alerting, orienting, and executive attention. Positive or negative mood was induced by listening to music with a positive or negative valence, respectively; neutral mood was induced by reading a collection of basic facts about China. The results revealed that negative mood led to a significantly higher alerting efficiency relative to other moods, while there were no significant mood effects on orienting or executive attention efficiency. According to the algorithm underlying the ANT, the higher alerting efficiency in the negative mood condition can be attributed to relatively greater benefits of cueing effects. The findings are discussed in the context of the noradrenergic system and of evolutionary significance. Specifically, the increase in the alerting function during negative mood states may be due to the modulation effect of negative mood on the noradrenergic system, and/or to the survival benefit resulting from an increase in automatic vigilance towards negative information. The current results suggest that as the influence of negative mood on attention appears to specifically consist in an enhanced alerting function, it may not be found in studies where the three attentional networks are not dissociated.

Mood and audience effects on video lottery terminal gambling.

PubMed

Mishra, Sandeep; Morgan, Michael; Lalumière, Martin L; Williams, Robert J

2010-09-01

Little is known about the situational factors associated with gambling behavior. We induced 180 male participants (mean age: 21.6) into a positive, negative, or neutral mood prior to gambling on a video lottery terminal (VLT). While gambling, participants were observed by either a male peer, female peer, or no one. Induced mood had no effect on gambling behavior. Participants induced into a negative mood prior to gambling, however, reported more positive moods after gambling, whereas those with positive and neutral moods reported more negative moods after gambling. Participants observed by either a male or female peer spent less time gambling on the VLT compared to those not observed. Participants observed by a female peer lost less money relative to the other observer conditions. Degree of problem gambling in the last year had little influence on these effects. Some practical implications of these findings are discussed.

The Effect of Drawing Exercises on Mood When Negative Affect Is Not Induced

ERIC Educational Resources Information Center

Northcott, Jessica L.; Frein, Scott T.

2017-01-01

In this study we examined the effects of drawing on positive and negative affect, when negative mood induction is not used as has been done in prior research. There were 64 participants ranging in age from 18 to 24 who completed 1 of the following activities: drawing, writing, or sitting quietly for 10 min. Positive and negative affects were…

Effects of induced and naturalistic mood on the temporal allocation of attention to emotional information.

PubMed

Farach, Frank J; Treat, Teresa A; Jungé, Justin A

2014-01-01

Building upon recent findings that affective states can influence the allocation of spatial attention, we investigate how state, trait and induced mood are related to the temporal allocation of attention to emotional information. In the present study, 125 unscreened undergraduates completed a modified rapid serial visual presentation task designed to assess the time course of attention to positive and negative information, comparing a neutral baseline mood induction to either a positive or negative mood induction. Induced negative mood facilitated attentional engagement to positive information while decreasing attentional engagement to negative information. Greater naturally occurring negative state mood was associated with faster or more efficient disengagement of attention from negative information in the presence of manipulated negative mood, relative to baseline. The engagement findings were inconsistent with our mood-congruence hypotheses and may be better explained by mood repair or affective counter-regulation theories. In contrast, the disengagement findings for state mood were somewhat consistent with our mood-congruence hypotheses. The relationship between mood and attention to emotional information may differ depending on the combination of attentional mechanism (engagement versus disengagement), aspect of mood (state, trait or induced), stimulus valence (positive versus negative) and timescale (early versus late) under investigation.

Nocebo phenomena in medicine: their relevance in everyday clinical practice.

PubMed

Häuser, Winfried; Hansen, Ernil; Enck, Paul

2012-06-01

Nocebo phenomena are common in clinical practice and have recently become a popular topic of research and discussion among basic scientists, clinicians, and ethicists. We selectively searched the PubMed database for articles published up to December 2011 that contained the key words "nocebo" or "nocebo effect." By definition, a nocebo effect is the induction of a symptom perceived as negative by sham treatment and/or by the suggestion of negative expectations. A nocebo response is a negative symptom induced by the patient's own negative expectations and/or by negative suggestions from clinical staff in the absence of any treatment. The underlying mechanisms include learning by Pavlovian conditioning and reaction to expectations induced by verbal information or suggestion. Nocebo responses may come about through unintentional negative suggestion on the part of physicians and nurses. Information about possible complications and negative expectations on the patient's part increases the likelihood of adverse effects. Adverse events under treatment with medications sometimes come about by a nocebo effect. Physicians face an ethical dilemma, as they are required not just to inform patients of the potential complications of treatment, but also to minimize the likelihood of these complications, i.e., to avoid inducing them through the potential nocebo effect of thorough patient information. Possible ways out of the dilemma include emphasizing the fact that the proposed treatment is usually well tolerated, or else getting the patient's permission to inform less than fully about its possible side effects. Communication training in medical school, residency training, and continuing medical education would be desirable so that physicians can better exploit the power of words to patients' benefit, rather than their detriment.

Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.

PubMed

Kanae, Haruna; Hamaguchi, Shogo; Wakasugi, Yumi; Kusakabe, Taichi; Kato, Keisuke; Namekata, Iyuki; Tanaka, Hikaru

2017-11-01

Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

mGlu₅-GABAB interplay in animal models of positive, negative and cognitive symptoms of schizophrenia.

PubMed

Wierońska, Joanna M; Kłeczek, Natalia; Woźniak, Monika; Gruca, Piotr; Łasoń-Tyburkiewicz, Magdalena; Papp, Mariusz; Brański, Piotr; Burnat, Grzegorz; Pilc, Andrzej

2015-09-01

Diverse preclinical studies exploiting the modulation of the GABAergic and/or glutamatergic system in brain via metabotropic receptors suggest their potential therapeutic utility. GS39783 and CDPPB, positive allosteric modulators of GABAB and mGlu5 receptors, were previously shown to reverse behavioral phenotypes in animal models to mimic selected (predominantly positive) symptoms of schizophrenia. In the present study we investigated the activity of selected GABAB (GS39783 and CGP7930) and mGlu5 (CDPPB) positive allosteric modulators. We focused mainly on the aspects of their efficacy in the models of negative and cognitive symptoms of schizophrenia. We used modified swim test, social interactions (models of negative symptoms) and novel object recognition (model of cognitive disturbances). The activity of the compounds was also tested in haloperidol-induced catalepsy test. The mutual interaction between GABAB/mGlu5 ligands was investigated as well. In the second part of the study, DHPG-induced PI hydrolysis in the presence of GABAB receptor antagonist (SKF97541), and SKF97541-induced inhibition of cAMP formation in the presence of DHPG, was performed. Both mGlu5 and GABAB receptor modulators effectively reversed MK-801-induced deficits in behavioral models of schizophrenia. Moreover, the concomitant administration of sub-effective doses of CDPPB and GS39783 induced a clear antipsychotic-like effect in all the procedures used, except DOI-induced head twitches. The concomitant administration of group I mGlu and GABAB agonists did not displayed any synergistic effects in vitro. Summing up, an activation of both types of receptor may be a promising mechanism for the development of novel antipsychotic drugs, efficacious toward positive, negative and cognitive symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mood effects on attitude judgments: independent effects of mood before and after message elaboration.

PubMed

Bless, H; Mackie, D M; Schwarz, N

1992-10-01

This study investigated the independent effects of induced mood on the encoding of persuasive messages and on the assessment of attitude judgments. In Experiment 1, positive or negative mood was induced either before the encoding of a counterattitudinal message or before the assessment of attitude judgments. When mood was induced before message presentation, Ss in a bad mood were more persuaded by strong than by weak arguments, whereas Ss in a good mood were equally persuaded by strong and by weak arguments. When Ss encoded the message in a neutral mood, however, the advantage of strong over weak arguments was more pronounced when Ss were in a good rather than in a bad mood at the time of attitude assessment. In Experiment 2, Ss exposed to a counterattitudinal message composed of either strong or weak arguments formed either a global evaluation or a detailed representation of the message. Positive, negative, or neutral mood was then induced. Ss in a good mood were most likely and Ss in a negative mood least likely to base their reported attitudes on global evaluations.

The triterpenoids of Hibiscus syriacus induce apoptosis and inhibit cell migration in breast cancer cells.

PubMed

Hsu, Ren-Jun; Hsu, Yao-Chin; Chen, Shu-Pin; Fu, Chia-Lynn; Yu, Jyh-Cherng; Chang, Fung-Wei; Chen, Ying-Hsin; Liu, Jui-Ming; Ho, Jar-Yi; Yu, Cheng-Ping

2015-03-14

Breast cancer-related mortality increases annually. The efficacy of current breast cancer treatments is limited, and they have numerous side effects and permit high recurrence. Patients with estrogen receptor (ER)-negative or triple-negative breast cancer are particularly difficult to treat. Treatment for this type of cancer is lacking, and its prognosis is poor, necessitating the search for alternative treatments. This study screened Chinese herb Hibiscus syriacus extracts and identified a novel anti-cancer drug for patients with ER-negative breast cancer. The inhibitory effects on cell viability and migration were evaluated for each compound, and the molecular regulatory effects were evaluated on both mRNA and protein levels. We found several triterpenoids including betulin (K02) and its derivatives (K03, K04, and K06) from H. syriacus inhibited human triple-negative breast cancer cell viability and migration but revealed smaller cytotoxic effects on normal mammalian epithelial cells. Betulin and its derivatives induced apoptosis by activating apoptosis-related genes. In addition, they activated p21 expression, which induced cell cycle arrest in breast cancer cells. Betulin (K02) and betulinic acid (K06) had stronger inhibitory effects on cell viability and migration than K03 and K04. H. syriacus extracts might inhibit breast cancer cell viability and induce apoptosis by activating p53 family regulated pathways and inhibiting AKT activation. H. syriacus extracts may provide important insight into the development of novel alternative therapies for breast cancer.

The influence of negative emotion on brand extension as reflected by the change of N2: a preliminary study.

PubMed

Ma, Qingguo; Wang, Kai; Wang, Xiaoyi; Wang, Cuicui; Wang, Lei

2010-11-26

The aim of the present study is to find the neural features of the impact of induced negative emotion on brand extension. Facing three sequential stimuli in triples consisted of negative emotion pictures (stimulus 1), beverage brand names (stimulus 2), and product names (stimulus 3) in other categories, 20 participants were asked to indicate the suitability of extending the brand in stimulus 2 to the product category in stimulus 3. The stimulus triples were divided into six conditions depending on the emotion (neutral and negative) and the extension product category in stimulus 3: beverage, clothing, and the household appliance. A negative component reflecting conflict, N2, was recorded for each condition on the subjects' scalp. The induced negative emotion elicited significantly larger amplitude of N2 than did the induced neutral emotion in the moderate extension type (extending to the clothing product), whereas no significant difference was observed in any of the other two extension types. The findings indicate that the induced negative emotion has a specific negative impact on moderate brand extension, and the amplitude of N2 can be viewed as a reference measure reflecting such effect. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

SR Ca2+-leak and disordered excitation-contraction coupling as the basis for arrhythmogenic and negative inotropic effects of acute ethanol exposure.

PubMed

Mustroph, Julian; Wagemann, Olivia; Lebek, Simon; Tarnowski, Daniel; Ackermann, Jasmin; Drzymalski, Marzena; Pabel, Steffen; Schmid, Christof; Wagner, Stefan; Sossalla, Samuel; Maier, Lars S; Neef, Stefan

2018-03-01

Ethanol has acute negative inotropic and arrhythmogenic effects. The underlying mechanisms, however, are largely unknown. Sarcoplasmic reticulum Ca 2+ -leak is an important mechanism for reduced contractility and arrhythmias. Ca 2+ -leak can be induced by oxidative stress and Ca 2+ /Calmodulin-dependent protein kinase II (CaMKII). Therefore, we investigated the influence of acute ethanol exposure on excitation-contraction coupling in atrial and ventricular cardiomyocytes. Isolated human atrial and murine atrial or ventricular cardiomyocytes were preincubated for 30 min and then superfused with control solution or solution containing ethanol. Ethanol had acute negative inotropic and positive lusitropic effects in human atrial muscle strips and murine ventricular cardiomyocytes. Accordingly, Ca 2+ -imaging indicated lower Ca 2+ -transient amplitudes and increased SERCA2a activity, while myofilament Ca 2+ -sensitivity was reduced. SR Ca 2+ -leak was assessed by measuring Ca 2+ -sparks. Ethanol induced severe SR Ca 2+ -leak in human atrial cardiomyocytes (calculated leak: 4.60 ± 0.45 mF/F 0 vs 1.86 ± 0.26 in control, n ≥ 80). This effect was dose-dependent, while spontaneous arrhythmogenic Ca 2+ -waves increased ~5-fold, as investigated in murine cardiomyocytes. Delayed afterdepolarizations, which can result from increased SR Ca 2+ -leak, were significantly increased by ethanol. Measurements using the reactive oxygen species (ROS) sensor CM-H 2 DCFDA showed increased ROS-stress in ethanol treated cells. ROS-scavenging with N-acetylcysteine prevented negative inotropic and positive lusitropic effects in human muscle strips. Ethanol-induced Ca 2+ -leak was abolished in mice with knockout of NOX2 (the main source for ROS in cardiomyocytes). Importantly, mice with oxidation-resistant CaMKII (Met281/282Val mutation) were protected from ethanol-induced Ca 2+ -leak. We show for the first time that ethanol acutely induces strong SR Ca 2+ -leak, also altering excitation-contraction coupling. Acute negative inotropic effects of ethanol can be explained by reduced systolic Ca 2+ -release. Mechanistically, ROS-production via NOX2 and oxidative activation of CaMKII appear to play central roles. This provides a mechanism for the arrhythmogenic and negative inotropic effects of ethanol and suggests a druggable target (CaMKII). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Calcitriol restores antiestrogen responsiveness in estrogen receptor negative breast cancer cells: a potential new therapeutic approach.

PubMed

Santos-Martínez, Nancy; Díaz, Lorenza; Ordaz-Rosado, David; García-Quiroz, Janice; Barrera, David; Avila, Euclides; Halhali, Ali; Medina-Franco, Heriberto; Ibarra-Sánchez, María J; Esparza-López, José; Camacho, Javier; Larrea, Fernando; García-Becerra, Rocío

2014-03-29

Approximately 30% of breast tumors do not express the estrogen receptor (ER) α, which is necessary for endocrine therapy approaches. Studies are ongoing in order to restore ERα expression in ERα-negative breast cancer. The aim of the present study was to determine if calcitriol induces ERα expression in ER-negative breast cancer cells, thus restoring antiestrogen responses. Cultured cells derived from ERα-negative breast tumors and an ERα-negative breast cancer cell line (SUM-229PE) were treated with calcitriol and ERα expression was assessed by real time PCR and western blots. The ERα functionality was evaluated by prolactin gene expression analysis. In addition, the effects of antiestrogens were assessed by growth assay using the XTT method. Gene expression of cyclin D1 (CCND1), and Ether-à-go-go 1 (EAG1) was also evaluated in cells treated with calcitriol alone or in combination with estradiol or ICI-182,780. Statistical analyses were determined by one-way ANOVA. Calcitriol was able to induce the expression of a functional ERα in ER-negative breast cancer cells. This effect was mediated through the vitamin D receptor (VDR), since it was abrogated by a VDR antagonist. Interestingly, the calcitriol-induced ERα restored the response to antiestrogens by inhibiting cell proliferation. In addition, calcitriol-treated cells in the presence of ICI-182,780 resulted in a significant reduction of two important cell proliferation regulators CCND1 and EAG1. Calcitriol induced the expression of ERα and restored the response to antiestrogens in ERα-negative breast cancer cells. The combined treatment with calcitriol and antiestrogens could represent a new therapeutic strategy in ERα-negative breast cancer patients.

Negative affect improves the quality of memories: trading capacity for precision in sensory and working memory.

PubMed

Spachtholz, Philipp; Kuhbandner, Christof; Pekrun, Reinhard

2014-08-01

Research has shown that negative affect reduces working memory capacity. Commonly, this effect has been attributed to an allocation of resources to task-irrelevant thoughts, suggesting that negative affect has detrimental consequences for working memory performance. However, rather than simply being a detrimental effect, the affect-induced capacity reduction may reflect a trading of capacity for precision of stored representations. To test this hypothesis, we induced neutral or negative affect and concurrently measured the number and precision of representations stored in sensory and working memory. Compared with neutral affect, negative affect reduced the capacity of both sensory and working memory. However, in both memory systems, this decrease in capacity was accompanied by an increase in precision. These findings demonstrate that observers unintentionally trade capacity for precision as a function of affective state and indicate that negative affect can be beneficial for the quality of memories. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Low dose or low dose rate ionizing radiation-induced health effect in the human.

PubMed

Tang, Feng Ru; Loganovsky, Konstantin

2018-06-05

The extensive literature review on human epidemiological studies suggests that low dose ionizing radiation (LDIR) (≤100 mSv) or low dose rate ionizing radiation (LDRIR) (<6mSv/H) exposure could induce either negative or positive health effects. These changes may depend on genetic background, age (prenatal day for embryo), sex, nature of radiation exposure, i.e., acute or chronic irradiation, radiation sources (such as atomic bomb attack, fallout from nuclear weapon test, nuclear power plant accidents, 60 Co-contaminated building, space radiation, high background radiation, medical examinations or procedures) and radionuclide components and human epidemiological experimental designs. Epidemiological and clinical studies show that LDIR or LDRIR exposure may induce cancer, congenital abnormalities, cardiovascular and cerebrovascular diseases, cognitive and other neuropsychiatric disorders, cataracts and other eye and somatic pathology (endocrine, bronchopulmonary, digestive, etc). LDIR or LDRIR exposure may also reduce mutation and cancer mortality rates. So far, the mechanisms of LDIR- or LDRIR -induced health effect are poorly understood. Further extensive studies are still needed to clarify under what circumstances, LDIR or LDRIR exposure may induce positive or negative effects, which may facilitate development of new therapeutic approaches to prevent or treat the radiation-induced human diseases or enhance radiation-induced positive health effect. Copyright © 2018 Elsevier Ltd. All rights reserved.

Does mood influence text processing and comprehension? Evidence from an eye-movement study.

PubMed

Scrimin, Sara; Mason, Lucia

2015-09-01

Previous research has indicated that mood influences cognitive processes. However, there is scarce data regarding the link between everyday emotional states and readers' text processing and comprehension. We aim to extend current research on the effects of mood induction on science text processing and comprehension, using eye-tracking methodology. We investigated whether a positive-, negative-, and neutral-induced mood influences online processing, as revealed by indices of visual behaviour during reading, and offline text comprehension, as revealed by post-test questions. We were also interested in the link between text processing and comprehension. Seventy-eight undergraduate students randomly assigned to three mood-induction conditions. Students were mood-induced by watching a video clip. They were then asked to read a scientific text while eye movements were registered. Pre- and post-reading knowledge was assessed through open-ended questions. Experimentally induced moods lead readers to process an expository text differently. Overall, students in a positive mood spent significantly longer on the text processing than students in the negative and neutral moods. Eye-movement patterns indicated more effective processing related to longer proportion of look-back fixation times in positive-induced compared with negative-induced readers. Students in a positive mood also comprehended the text better, learning more factual knowledge, compared with students in the negative group. Only for the positive-induced readers did the more purposeful second-pass reading positively predict text comprehension. New insights are given on the effects of normal mood variations and students' text processing and comprehension by the use of eye-tracking methodology. Important implications for the role of emotional states in educational settings are highlighted. © 2015 The British Psychological Society.

[Children with hyperthyroidism due to elevated hCG levels].

PubMed

Jöbsis, Jasper J; van Trotsenburg, A S Paul; Merks, Johannes H M; Kamp, Gerdine A

2014-01-01

We describe two children with hyperthyroidism secondary to elevated hCG levels: one patient with gestational trophoblastic disease and one patient with choriocarcinoma. hCG resembles other glycoproteins that can lead to hyperthyroidism through TSH receptor activation. Also, through its LH-mimicking effect, hCG can induce high oestradiol levels, resulting in stormy pubertal development. False negative hCG tests due to the high-dose hook effect may complicate the diagnostic process. In patients with antibody-negative thyrotoxicosis, the diagnosis of hCG-induced hyperthyroidism must be considered.

Stereotype threat and performance: how self-stereotypes influence processing by inducing regulatory foci.

PubMed

Seibt, Beate; Förster, Jens

2004-07-01

The authors hypothesized that activated self-stereotypes can influence the strategies of task solution by inducing regulatory foci. More specifically, positive self-stereotypes should induce a promotion focus state of eagerness, whereas negative stereotypes should induce a prevention focus state of vigilance. Study 1 showed that a negative ascribed stereotype with regard to task performance leads to better recall for avoidance-related statements whereas a positive stereotype leads to better recall for approach-related statements. In Studies 2 and 3, both an experimental manipulation of group performance expectation and the preexisting stereotype of better verbal skills in women than in men led to faster and less accurate performance in the positive as compared with the negative stereotype group. Studies 4 and 5 showed that positive in-group stereotypes led to more creative performance whereas negative stereotypes led to better analytical performance. These results point to a possible mechanism for stereotype-threat effects. Copyright 2004 American Psychological Association

Placebo and Nocebo Effects in Sexual Medicine: An Experimental Approach.

PubMed

Kruger, Tillmann H C; Grob, Carolin; de Boer, Claas; Peschel, Thomas; Hartmann, Uwe; Tenbergen, Gilian; Schedlowski, Manfred

2016-11-16

Few studies have investigated placebo and nocebo effects in a human sexuality context. Studying placebo and nocebo responses in this context may provide insight into their potential to modulate sexual drive and function. To examine such effects in sexual medicine, 48 healthy, male heterosexual participants were divided into four groups. Each group received instruction to expect stimulating effects, no effect, or an inhibitory effect on sexual functions. Only one group received the dopamine agonist cabergoline; all other groups received placebo or nocebo. Modulations in sexual experience were examined through an established experimental paradigm of sexual arousal and masturbation-induced orgasm during erotic film sequences with instruction to induce placebo or nocebo effects. Endocrine data, appetitive, consummatory, and refractory sexual behavior parameters were assessed using the Arizona Sexual Experience Scale (ASEX) and the Acute Sexual Experience Scale (ASES). Results showed increased levels of sexual function after administration of cabergoline with significant effects for several parameters. Placebo effects were induced only to a small degree. No negative effects on sexual parameters in the nocebo condition were noted. This paradigm could induce only small placebo and nocebo effects. This supports the view that healthy male sexual function seems relatively resistant to negative external influences.

PKC{eta} is a negative regulator of AKT inhibiting the IGF-I induced proliferation

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

Shahaf, Galit; Rotem-Dai, Noa; Koifman, Gabriela

2012-04-15

The PI3K-AKT pathway is frequently activated in human cancers, including breast cancer, and its activation appears to be critical for tumor maintenance. Some malignant cells are dependent on activated AKT for their survival; tumors exhibiting elevated AKT activity show sensitivity to its inhibition, providing an Achilles heel for their treatment. Here we show that the PKC{eta} isoform is a negative regulator of the AKT signaling pathway. The IGF-I induced phosphorylation on Ser473 of AKT was inhibited by the PKC{eta}-induced expression in MCF-7 breast adenocarcinoma cancer cells. This was further confirmed in shRNA PKC{eta}-knocked-down MCF-7 cells, demonstrating elevated phosphorylation on AKTmore » Ser473. While PKC{eta} exhibited negative regulation on AKT phosphorylation it did not alter the IGF-I induced ERK phosphorylation. However, it enhanced ERK phosphorylation when stimulated by PDGF. Moreover, its effects on IGF-I/AKT and PDGF/ERK pathways were in correlation with cell proliferation. We further show that both PKC{eta} and IGF-I confer protection against UV-induced apoptosis and cell death having additive effects. Although the protective effect of IGF-I involved activation of AKT, it was not affected by PKC{eta} expression, suggesting that PKC{eta} acts through a different route to increase cell survival. Hence, our studies show that PKC{eta} provides negative control on AKT pathway leading to reduced cell proliferation, and further suggest that its presence/absence in breast cancer cells will affect cell death, which could be of therapeutic value.« less

The effects of negative and positive mood induction on eating behaviour: A meta-analysis of laboratory studies in the healthy population and eating and weight disorders.

PubMed

Cardi, Valentina; Leppanen, Jenni; Treasure, Janet

2015-10-01

The aim of this study was to conduct a meta-analysis to quantify the effect of induced negative and positive mood on meal consumption in healthy participants and patients with eating and weight disorders. The search term "MOOD" was combined with the following keywords: "TEST MEAL" or "LABORATORY FEEDING" or "LABORATORY MEAL" or "TASTE TEST" or "TASTE TASK" to identify the relevant studies. Thirty-three studies were selected, including 2491 participants. Two meta-analyses compared negative mood or positive mood with neutral mood. Induced negative mood was significantly associated with greater food intake, especially in restrained eaters and binge eaters. Positive mood was also associated with greater caloric intake across groups. These findings support the causal relationship between negative mood and greater food intake, especially in restrained eaters and binge eaters. Preliminary evidence indicates that strategies to improve positive mood might be of benefit for people with anorexia nervosa and bulimia nervosa, although the size of the effect across a single meal is small. Copyright © 2015 Elsevier Ltd. All rights reserved.

Surgical treatment is effective in severe cases of exercise-induced laryngeal obstruction: A follow-up study.

PubMed

Norlander, Katarina; Johansson, Henrik; Jansson, Christer; Nordvall, Lennart; Nordang, Leif

2015-01-01

Surgery is an effective treatment in severe cases of supraglottic exercise-induced laryngeal obstruction (E-ILO). Conservatively treated subjects and subjects tested negative for E-ILO, who still experience breathing problems 1-3 years after diagnosis, tend to adjust their physical activity to a greater extent than surgically treated subjects. To investigate how symptoms and level of physical activity change over time in patients with E-ILO who have undergone surgery, patients with E-ILO treated conservatively and patients who tested negative for laryngeal obstruction at continuous laryngoscopy exercise-test (CLE-test). Patients referred for exercise-induced breathing difficulties answered questionnaires at diagnostic CLE-test and at follow-up. Questions regarded exercise-induced breathing problems, current physical activity level, and medical history of asthma and perennial allergy. Out of 84 invited subjects, 59 (70%) answered both questionnaires. Surgically treated subjects had less breathing problems at follow-up compared with conservatively treated subjects and subjects who tested negative (p < 0.001). None of the surgically treated subjects were less physically active or had changed sport due to exercise-induced dyspnoea, whereas 41.7% of the conservatively treated subjects had made such adjustments (p < 0.001).

Metformin sensitizes triple-negative breast cancer to proapoptotic TRAIL receptor agonists by suppressing XIAP expression.

PubMed

Strekalova, Elena; Malin, Dmitry; Rajanala, Harisha; Cryns, Vincent L

2017-06-01

Despite robust antitumor activity in diverse preclinical models, TNF-related apoptosis-inducing ligand (TRAIL) receptor agonists have not demonstrated efficacy in clinical trials, underscoring the need to identify agents that enhance their activity. We postulated that the metabolic stress induced by the diabetes drug metformin would sensitize breast cancer cells to TRAIL receptor agonists. Human triple (estrogen receptor, progesterone receptor, and HER2)-negative breast cancer (TNBC) cell lines were treated with TRAIL receptor agonists (monoclonal antibodies or TRAIL peptide), metformin, or the combination. The effects on cell survival, caspase activation, and expression of TRAIL receptors and the antiapoptotic protein XIAP were determined. In addition, XIAP was silenced by RNAi in TNBC cells and the effects on sensitivity to TRAIL were determined. The antitumor effects of metformin, TRAIL, or the combination were evaluated in an orthotopic model of metastatic TNBC. Metformin sensitized diverse TNBC cells to TRAIL receptor agonists. Metformin selectively enhanced the sensitivity of transformed breast epithelial cells to TRAIL receptor agonist-induced caspase activation and apoptosis with little effect on untransformed breast epithelial cells. These effects of metformin were accompanied by robust reductions in the protein levels of XIAP, a negative regulator of TRAIL-induced apoptosis. Silencing XIAP in TNBC cells mimicked the TRAIL-sensitizing effects of metformin. Metformin also enhanced the antitumor effects of TRAIL in a metastatic murine TNBC model. Our findings indicate that metformin enhances the activity of TRAIL receptor agonists, thereby supporting the rationale for additional translational studies combining these agents.

The effect of evaluation on co-occurrence memory judgement.

PubMed

Bar-Anan, Yoav; Amzaleg-David, Efrat

2014-01-01

Three experiments tested the effect of an attitude towards an object on the memory judgement of whether this object co-occurred with positive versus negative stimuli. We induced positive or negative attitudes towards novel male stimuli, and paired each man with an equal number of positive and negative animals. In a memory test, participants reported more co-occurrences of same-valence man/animal pairs than opposite-valence pairs. This valence-compatibility effect occurred even when attitudes were induced after the pairing (Experiment 1), when participants knew that each man occurred with an equal number of positive and negative animals (Experiment 2), and in reports of clear memory of pairs that did not co-occur (Experiment 3). The present findings suggest that evaluation causes illusory correlation even when the co-occurring stimuli are not traits or behaviours attributed to the attitude object. The results question the validity of co-occurrence memory judgements as measures of co-occurrence awareness in evaluative conditioning (EC) research.

Temperature induced phase transformations and negative electrocaloric effect in (Pb,La)(Zr,Sn,Ti)O3 antiferroelectric single crystal

NASA Astrophysics Data System (ADS)

Zhuo, Fangping; Li, Qiang; Yan, Qingfeng; Zhang, Yiling; Wu, Hong-Hui; Xi, Xiaoqing; Chu, Xiangcheng; Cao, Wenwu

2017-10-01

Temperature induced phase transitions and electrocaloric effect (ECE) of (Pb,La)(Zr,Sn,Ti)O3 (PLZST) single crystals have been comprehensively studied. Based on the in situ evolution of domain structures and dielectric properties of the PLZST crystals, the phase transitions during heating are in the sequence of orthorhombic antiferroelectric → rhombohedral ferroelectric → cubic paraelectric. Coexistence of the negative and positive ECEs has been achieved in the PLZST single crystals. A negative ECE value of -1.26 °C and enhanced electrocaloric strength of -0.21 K mm/kV near the Curie temperature have been obtained. A modified Landau model gives a satisfactory description of the experimentally observed unusual ECE. Moreover, a temperature-electric field phase diagram is also established based on theoretical analysis. Our results will help people understand better the electrocaloric family, particularly on the negative and/or positive effect in antiferroelectrics and ferroelectrics.

Predictors of urge to smoke under stressful conditions: An experimental investigation utilizing the PASAT-C task to induce negative affect in smokers.

PubMed

Karekla, Maria; Panayiotou, Georgia; Collins, Bradley N

2017-11-01

Experimental evidence has demonstrated that the presence of cues previously associated with smoking behavior can increase urges to smoke in abstinent smokers. This study examined the effect of a laboratory-induced negative affective task (paced auditory serial addition task) on smoking urges among a sample of 35 abstinent college smokers (Mage = 20.83 years, SD = 1.71). Emotional states and physiological reactions experienced during the experiment, as well as individual differences in stress intolerance (anxiety sensitivity and experiential avoidance) were examined as predictors of the association between stressful states and smoking cravings. Smoking urges (smoking desire and negative affect relief) and negative emotions (frustration, irritability, stress) significantly increased, whereas positive emotions decreased from pre- to posttask. No significant interactions between individual differences and changes in urge were found. Results suggest that changes in negative affect may in part explain the association between induced stress and smoking cravings. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Tragedy or tragicomedy: Mixed feelings induced by positive and negative emotional events.

PubMed

Xia, Mu; Chen, Jie; Li, Hong

2016-08-01

Based on the theory of appraisal, we predicted that positive and negative events happening to the same people or things in a specific chronological order (i.e., a negative event following a positive event) would induce different mixed feelings than the same events happening to different people or things. Pairs of emotional pictures with different captions were used to create two event groups. In the "tragic event" group, the positive and negative events happened to the same person or things, and in the "tragicomic event" group, the positive and negative events happened to different people or things. We designed two experiments to explore and compare the generation of mixed feelings in those two groups. In Experiment 1, the negative event was shown first, and in Experiment 2, the negative event was shown second (although the chronological order of the depicted events was the same). The participants were 381 undergraduates: 195 in Experiment 1 and 186 in Experiment 2. In both experiments, we found that tragic events introduced less intense mixed feelings than did tragicomic events due to fewer pleasurable feelings induced by the tragic events. There was no significant difference in the report of negative emotions between the groups. Appraisal theory and negative bias effects may explain these results.

Light-induced negative differential resistance in gate-controlled graphene-silicon photodiode

NASA Astrophysics Data System (ADS)

Liu, Wei; Guo, Hongwei; Li, Wei; Wan, Xia; Bodepudi, Srikrishna Chanakya; Shehzad, Khurram; Xu, Yang

2018-05-01

In this letter, we investigated light-induced negative differential resistance (L-NDR) effects in a hybrid photodiode formed by a graphene-silicon (GS) junction and a neighboring graphene-oxide-Si (GOS) capacitor. We observed two distinct L-NDR effects originating from the gate-dependent surface recombination and the potential-well-induced confinement of photo-carriers in the GOS region. We verified this by studying the gate-controlled GS diode, which can distinguish the photocurrent from the GS region with that from the GOS region (gate). A large peak-to-valley ratio of up to 12.1 has been obtained for the L-NDR due to gate-dependent surface recombination. Such strong L-NDR effect provides an opportunity to further engineer the optoelectronic properties of GS junctions along with exploring its potential applications in photodetectors, photo-memories, and position sensitive devices.

Unhappiness Intensifies the Avoidance of Frequent Losses While Happiness Overcomes It.

PubMed

Yechiam, Eldad; Telpaz, Ariel; Krupenia, Stas; Rafaeli, Anat

2016-01-01

The implication of spontaneous and induced unhappiness to people's decision style is examined. It is postulated that unhappy individuals have a greater tendency to avoid frequent losses because these can have depleting effects, and unhappy individuals are more sensitive to such effects. This is evaluated in Study 1 by using an annoying customer call manipulation to induce negative affect; and by examining the effect of this manipulation on choices in an experiential decision task (the Iowa Gambling task). In Study 2 we examined the association between self-reported (un)happiness and choices on the same decision task. In Study 1 the induction of negative affect led to avoidance of choice alternatives with frequent losses, compared to those yielding rarer but larger losses. Specifically, this pertained to the advantageous alternatives with frequent vs. non-frequent losses. In Study 2 unhappiness was similarly associated with less exposure to frequent losses; while extreme high happiness was associated with no tendency to avoid frequent losses when these were part of an advantageous alternative. The findings clarify the role of happiness in decision making processes by indicating that unhappiness induces sensitivity to the frequency rather than to the total effect of negative events.

Unhappiness Intensifies the Avoidance of Frequent Losses While Happiness Overcomes It

PubMed Central

Yechiam, Eldad; Telpaz, Ariel; Krupenia, Stas; Rafaeli, Anat

2016-01-01

The implication of spontaneous and induced unhappiness to people's decision style is examined. It is postulated that unhappy individuals have a greater tendency to avoid frequent losses because these can have depleting effects, and unhappy individuals are more sensitive to such effects. This is evaluated in Study 1 by using an annoying customer call manipulation to induce negative affect; and by examining the effect of this manipulation on choices in an experiential decision task (the Iowa Gambling task). In Study 2 we examined the association between self-reported (un)happiness and choices on the same decision task. In Study 1 the induction of negative affect led to avoidance of choice alternatives with frequent losses, compared to those yielding rarer but larger losses. Specifically, this pertained to the advantageous alternatives with frequent vs. non-frequent losses. In Study 2 unhappiness was similarly associated with less exposure to frequent losses; while extreme high happiness was associated with no tendency to avoid frequent losses when these were part of an advantageous alternative. The findings clarify the role of happiness in decision making processes by indicating that unhappiness induces sensitivity to the frequency rather than to the total effect of negative events. PMID:27853443

Mitragyna speciosa Leaf Extract Exhibits Antipsychotic-Like Effect with the Potential to Alleviate Positive and Negative Symptoms of Psychosis in Mice

PubMed Central

Vijeepallam, Kamini; Pandy, Vijayapandi; Kunasegaran, Thubasni; Murugan, Dharmani D.; Naidu, Murali

2016-01-01

In this study, we investigated the antipsychotic-like effect of methanolic extract of Mitragyna speciosa leaf (MMS) using in vivo and ex vivo studies. In vivo studies comprised of apomorphine-induced climbing behavior, haloperidol-induced catalepsy, and ketamine-induced social withdrawal tests in mice whereas the ex vivo study was conducted utilizing isolated rat vas deferens preparation. Acute oral administration of MMS (50–500 mg/kg) showed an inverted bell-shaped dose-response in apomorphine-induced cage climbing behavior in mice. The effective inhibitory doses of MMS (75 and 100 mg/kg, p.o.) obtained from the apomorphine study was further tested on haloperidol (subcataleptic dose; 0.1 mg/kg, i.p.)-induced catalepsy in the mouse bar test. MMS (75 and 100 mg/kg, p.o.) significantly potentiated the haloperidol-induced catalepsy in mice. Interestingly, MMS at the same effective doses (75 and 100 mg/kg, p.o.) significantly facilitated the social interaction in ketamine-induced social withdrawal mice. Furthermore, MMS inhibited the dopamine-induced contractile response dose-dependently in the isolated rat vas deferens preparations. In conclusion, this investigation provides first evidence that MMS exhibits antipsychotic-like activity with potential to alleviate positive as well as negative symptoms of psychosis in mice. This study also suggests the antidopaminergic activity of MMS that could be responsible for alleviating positive symptoms of psychosis. PMID:27999544

Peripheral Pain Enhances the Effects of Incentive Downshifts

ERIC Educational Resources Information Center

Ortega, Leonardo A.; Daniel, Alan M.; Davis, Jessica B.; Fuchs, Perry N.; Papini, Mauricio R.

2011-01-01

Physical pain (induced by tissue damage) and psychological pain (induced by surprising incentive loss) share a set of common neural substrates, but little is known about their interactions. The present research studied such interactions using the formalin test to induce physical pain and consummatory successive negative contrast (cSNC) to induce…

Direct Manipulation of Physiological Arousal in Induced Anxiety Therapy-Biofeedback Approach

ERIC Educational Resources Information Center

Sappington, A. A.

1977-01-01

Induced Anxiety is a brief psychotherapy procedure that teaches individuals to cope with negative effect by using relaxation techniques. This research investigated the role of physiological arousal in the affect induction phase of Induced Anxiety therapy by using biofeedback to facilitate arousal. Twenty-one college students suffering from…

rTMS stimulation on left DLPFC affects emotional cue retrieval as a function of anxiety level and gender.

PubMed

Balconi, Michela; Ferrari, Chiara

2012-11-01

Anxiety behaviour showed a consistent attentional bias toward negative and aversive memories, induced by a right dorsolateral prefrontal cortex (DLPFC) hyperactivation. In the present research, we explored the possible effect of rTMS (repeated transcranial magnetic stimulation) on the left DLPFC in memory retrieval of positive versus negative emotional words, to induce a balanced response between the two hemispheres. Moreover, the gender effect in emotional memory processing was verified as a function of the stimulus valence. Thirty subjects, who were divided in two different groups depending on their anxiety level (high/low anxiety, State-Trait-Anxiety Inventory (STAI)), were required to perform a task consisting of two experimental phases: an encoding phase (lists composed by positive and negative emotional words); and a retrieval phase (old stimuli and new stimuli to be recognized). We found that the rTMS stimulation over left DLPFC affects the memory retrieval. Specifically, high-anxiety subjects benefitted in greater measure to the frontal left stimulation with a reduced negative bias (increased accuracy and reduced response time (RT) for the positive stimuli). Whereas females showed a significant bias toward the negative memories, they did not benefit in greater measure to the TMS stimulation on the left hemisphere. These results suggested that left DLPFC activation favors the memory retrieval of positive emotional information and may limit the "unbalance effect" induced by a right frontal hemispheric superiority in high levels of anxiety. © 2012 Wiley Periodicals, Inc.

The Effects of Transient Emotional State and Workload on Size Scaling in Perspective Displays

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

Tuan Q. Tran; Kimberly R. Raddatz

2006-10-01

Previous research has been devoted to the study of perceptual (e.g., number of depth cues) and cognitive (e.g., instructional set) factors that influence veridical size perception in perspective displays. However, considering that perspective displays have utility in high workload environments that often induce high arousal (e.g., aircraft cockpits), the present study sought to examine the effect of observers’ emotional state on the ability to perceive and judge veridical size. Within a dual-task paradigm, observers’ ability to make accurate size judgments was examined under conditions of induced emotional state (positive, negative, neutral) and high and low workload. Results showed that participantsmore » in both positive and negative induced emotional states were slower to make accurate size judgments than those not under induced emotional arousal. Results suggest that emotional state is an important factor that influences visual performance on perspective displays and is worthy of further study.« less

How the Emotional Content of Discourse Affects Language Comprehension

PubMed Central

Jiménez-Ortega, Laura; Martín-Loeches, Manuel; Casado, Pilar; Sel, Alejandra; Fondevila, Sabela; de Tejada, Pilar Herreros; Schacht, Annekathrin; Sommer, Werner

2012-01-01

Emotion effects on cognition have often been reported. However, only few studies investigated emotional effects on subsequent language processing, and in most cases these effects were induced by non-linguistic stimuli such as films, faces, or pictures. Here, we investigated how a paragraph of positive, negative, or neutral emotional valence affects the processing of a subsequent emotionally neutral sentence, which contained either semantic, syntactic, or no violation, respectively, by means of event-related brain potentials (ERPs). Behavioral data revealed strong effects of emotion; error rates and reaction times increased significantly in sentences preceded by a positive paragraph relative to negative and neutral ones. In ERPs, the N400 to semantic violations was not affected by emotion. In the syntactic experiment, however, clear emotion effects were observed on ERPs. The left anterior negativity (LAN) to syntactic violations, which was not visible in the neutral condition, was present in the negative and positive conditions. This is interpreted as reflecting modulatory effects of prior emotions on syntactic processing, which is discussed in the light of three alternative or complementary explanations based on emotion-induced cognitive styles, working memory, and arousal models. The present effects of emotion on the LAN are especially remarkable considering that syntactic processing has often been regarded as encapsulated and autonomous. PMID:22479432

The Context Matters: Outcome Probability and Expectation Mismatch Modulate the Feedback Negativity When Self-Evaluation of Response Correctness Is Possible

PubMed Central

Leue, Anja; Cano Rodilla, Carmen; Beauducel, André

2015-01-01

Individuals typically evaluate whether their performance and the obtained feedback match. Previous research has shown that feedback negativity (FN) depends on outcome probability and feedback valence. It is, however, less clear to what extent previous effects of outcome probability on FN depend on self-evaluations of response correctness. Therefore, we investigated the effects of outcome probability on FN amplitude in a simple go/no-go task that allowed for the self-evaluation of response correctness. We also investigated effects of performance incompatibility and feedback valence. In a sample of N = 22 participants, outcome probability was manipulated by means of precues, feedback valence by means of monetary feedback, and performance incompatibility by means of feedback that induced a match versus mismatch with individuals' performance. We found that the 100% outcome probability condition induced a more negative FN following no-loss than the 50% outcome probability condition. The FN following loss was more negative in the 50% compared to the 100% outcome probability condition. Performance-incompatible loss resulted in a more negative FN than performance-compatible loss. Our results indicate that the self-evaluation of the correctness of responses should be taken into account when the effects of outcome probability and expectation mismatch on FN are investigated. PMID:26783525

The Context Matters: Outcome Probability and Expectation Mismatch Modulate the Feedback Negativity When Self-Evaluation of Response Correctness Is Possible.

PubMed

Leue, Anja; Cano Rodilla, Carmen; Beauducel, André

2015-01-01

Individuals typically evaluate whether their performance and the obtained feedback match. Previous research has shown that feedback negativity (FN) depends on outcome probability and feedback valence. It is, however, less clear to what extent previous effects of outcome probability on FN depend on self-evaluations of response correctness. Therefore, we investigated the effects of outcome probability on FN amplitude in a simple go/no-go task that allowed for the self-evaluation of response correctness. We also investigated effects of performance incompatibility and feedback valence. In a sample of N = 22 participants, outcome probability was manipulated by means of precues, feedback valence by means of monetary feedback, and performance incompatibility by means of feedback that induced a match versus mismatch with individuals' performance. We found that the 100% outcome probability condition induced a more negative FN following no-loss than the 50% outcome probability condition. The FN following loss was more negative in the 50% compared to the 100% outcome probability condition. Performance-incompatible loss resulted in a more negative FN than performance-compatible loss. Our results indicate that the self-evaluation of the correctness of responses should be taken into account when the effects of outcome probability and expectation mismatch on FN are investigated.

Estrogen stimulated migration and invasion of estrogen receptor-negative breast cancer cells involves an ezrin-dependent crosstalk between G protein-coupled receptor 30 and estrogen receptor beta signaling.

PubMed

Zhou, Kewen; Sun, Peng; Zhang, Yaxing; You, Xinchao; Li, Ping; Wang, Tinghuai

2016-07-01

Estrogen mediates important cellular activities in estrogen receptor negative (ER-) breast cancer cells via membrane associated G protein-coupled receptor 30 (GPR30). However, the biological role and mechanism of estrogen action on cell motility and invasion in this aggressive kind of tumors remains poorly understood. We showed here that treatment with 17β-estradiol (E2) in ER-negative cancer cells resulted in ezrin-dependent cytoskeleton rearrangement and elicited a stimulatory effect on cell migration and invasion. Mechanistically, E2 induced ezrin activation was mediated by distinct mechanisms in different cell contexts. In SK-BR-3 cells with a high GPR30/ERβ ratio, silencing of GPR30 was able to abolish E2 induced ERK1/2, AKT phosphorylation and ezrin activation, whereas in MDA-MB-231 cells with low GPR30/ERβ ratio, E2 stimulated ezrin activation was mediated by the ERβ/PI3K/AKT signaling pathway. Importantly, we showed that activation of GPR30 signaling significantly prevents ERβ activation induced ezrin phosphorylation, cell migration and invasion, indicating an antagonist effect between GPR30 and ERβ signaling in MDA-MB-231 cells. These findings highlight the important interplay between different estrogen receptors in estrogen induced cell motility and invasiveness in ER-negative breast cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

The influence of presentation format on the "bigger is better" (BIB) effect.

PubMed

Bromgard, Gregg D; Trafimow, David; Silvera, David H

2013-04-01

Two experiments tested the "bigger is better" (BIB) effect, whereby bigger objects are perceived more favorably than smaller ones. In Experiment 1, participants directly compared pairs of objects and a strong BIB effect was obtained for both positively and negatively valenced stimuli. In Experiment 2, comparative and absolute evaluations were combined in a single experiment and the BIB effect was mediated for positively and negatively valenced stimuli. Taken in combination, the data support a complex hypothesis that pair-wise presentations induce a comparative process that causes a BIB effect. But when objects are evaluated separately, size and valence interact such that increased size evokes more positive ratings of positive objects and more negative ratings for negative objects.

Hyperglycaemia-induced chemoresistance in breast cancer cells: role of the estrogen receptor.

PubMed

Zeng, L; Zielinska, H A; Arshad, A; Shield, J P; Bahl, A; Holly, J M P; Perks, C M

2016-02-01

Breast cancer patients with diabetes respond less well to chemotherapy; in keeping with this we determined previously that hyperglycaemia-induced chemoresistance in estrogen receptor (ERα) positive breast cancer cells and showed that this was mediated by fatty acid synthase (FASN). More recent evidence suggests that the effect of metabolic syndrome and diabetes is not the same for all subtypes of breast cancer with inferior disease-free survival and worse overall survival only found in women with ERα positive breast cancer and not for other subtypes. Here we examined the impact of hyperglycaemia on ERα negative breast cancer cells and further investigated the mechanism underlying chemoresistance in ERα with a view to identifying strategies to alleviate hyperglycaemia-induced chemoresistance. We found that hyperglycaemia-induced chemoresistance was only observed in ERα breast cancer cells and was dependent upon the expression of ERα as chemoresistance was negated when the ERα was silenced. Hyperglycaemia-induced an increase in activation and nuclear localisation of the ERα that was downstream of FASN and dependent on the activation of MAPK. We found that fulvestrant successfully negated the hyperglycaemia-induced chemoresistance, whereas tamoxifen had no effect. In summary our data suggests that the ERα may be a predictive marker of poor response to chemotherapy in breast cancer patients with diabetes. It further indicates that anti-estrogens could be an effective adjuvant to chemotherapy in such patients and indicates the importance for the personalised management of breast cancer patients with diabetes highlighting the need for clinical trials of tailored chemotherapy for diabetic patients diagnosed with ERα positive breast cancers. © 2016 Society for Endocrinology.

Changing the conversation: the influence of emotions on conversational valence and alcohol consumption.

PubMed

Hendriks, Hanneke; van den Putte, Bas; de Bruijn, Gert-Jan

2014-10-01

Health campaign effects may be improved by taking interpersonal communication processes into account. The current study, which employed an experimental, pretest-posttest, randomized exposure design (N = 208), investigated whether the emotions induced by anti-alcohol messages influence conversational valence about alcohol and subsequent persuasion outcomes. The study produced three main findings. First, an increase in the emotion fear induced a negative conversational valence about alcohol. Second, fear was most strongly induced by a disgusting message, whereas a humorous appeal induced the least fear. Third, a negative conversational valence elicited healthier binge drinking attitudes, subjective norms, perceived behavioral control, intentions, and behaviors. Thus, health campaign planners and health researchers should pay special attention to the emotional characteristics of health messages and should focus on inducing a healthy conversational valence.

Half-metallic properties, single-spin negative differential resistance, and large single-spin Seebeck effects induced by chemical doping in zigzag-edged graphene nanoribbons

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

Yang, Xi-Feng; Zhou, Wen-Qian; Hong, Xue-Kun

2015-01-14

Ab initio calculations combining density-functional theory and nonequilibrium Green’s function are performed to investigate the effects of either single B atom or single N atom dopant in zigzag-edged graphene nanoribbons (ZGNRs) with the ferromagnetic state on the spin-dependent transport properties and thermospin performances. A spin-up (spin-down) localized state near the Fermi level can be induced by these dopants, resulting in a half-metallic property with 100% negative (positive) spin polarization at the Fermi level due to the destructive quantum interference effects. In addition, the highly spin-polarized electric current in the low bias-voltage regime and single-spin negative differential resistance in the highmore » bias-voltage regime are also observed in these doped ZGNRs. Moreover, the large spin-up (spin-down) Seebeck coefficient and the very weak spin-down (spin-up) Seebeck effect of the B(N)-doped ZGNRs near the Fermi level are simultaneously achieved, indicating that the spin Seebeck effect is comparable to the corresponding charge Seebeck effect.« less

Negative induced mood influences word production: An event-related potentials study with a covert picture naming task.

PubMed

Hinojosa, J A; Fernández-Folgueiras, U; Albert, J; Santaniello, G; Pozo, M A; Capilla, A

2017-01-27

The present event-related potentials (ERPs) study investigated the effects of mood on phonological encoding processes involved in word generation. For this purpose, negative, positive and neutral affective states were induced in participants during three different recording sessions using short film clips. After the mood induction procedure, participants performed a covert picture naming task in which they searched letters. The negative compared to the neutral mood condition elicited more negative amplitudes in a component peaking around 290ms. Furthermore, results from source localization analyses suggested that this activity was potentially generated in the left prefrontal cortex. In contrast, no differences were found in the comparison between positive and neutral moods. Overall, current data suggest that processes involved in the retrieval of phonological information during speech generation are impaired when participants are in a negative mood. The mechanisms underlying these effects were discussed in relation to linguistic and attentional processes, as well as in terms of the use of heuristics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Negative mood-induced alcohol-seeking is greater in young adults who report depression symptoms, drinking to cope, and subjective reactivity.

PubMed

Hogarth, Lee; Hardy, Lorna; Mathew, Amanda R; Hitsman, Brian

2018-04-01

Acute negative mood powerfully motivates alcohol-seeking behavior, but it remains unclear whether sensitivity to this effect is greater in drinkers who report depression symptoms, drinking to cope, and subjective reactivity. To examine these questions, 128 young adult alcohol drinkers (ages 18-25) completed questionnaires of alcohol use disorder symptoms, depression symptoms, and drinking to cope with negative affect. Baseline alcohol choice was measured by preference to enlarge alcohol versus food thumbnail images in two-alternative forced-choice trials. Negative mood was then induced by depressive statements and music, before alcohol choice was tested. Subjective reactivity was indexed by increased sadness pre- to post-mood induction. Baseline alcohol choice correlated with alcohol dependence symptoms (p = .001), and drinking coping motives (ps ≤ .01). Mood induction increased alcohol choice and subjective sadness overall (ps < .001). The mood-induced increase in alcohol choice was associated with depression symptoms (p = .007), drinking to cope (ps ≤ .03), and subjective reactivity (p = .007). The relationship between mood-induced alcohol choice and drinking to cope remained significant after covarying for other drinking motives. Furthermore, the three predictors (depression, drinking to cope, and subjective reactivity) accounted for unique variance in mood-induced alcohol choice (ps ≥ .03), and collectively accounted for 18% of the variance (p < .001). These findings validate the pictorial alcohol choice task as sensitive to the relative value of alcohol and acute negative mood. The findings also accord with the core prediction of negative reinforcement theory that sensitivity to the motivational impact of negative mood on alcohol-seeking behavior may be an important mechanism that links depression and alcohol dependence. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Negative Mood-Induced Alcohol-Seeking Is Greater in Young Adults Who Report Depression Symptoms, Drinking to Cope, and Subjective Reactivity

PubMed Central

2018-01-01

Acute negative mood powerfully motivates alcohol-seeking behavior, but it remains unclear whether sensitivity to this effect is greater in drinkers who report depression symptoms, drinking to cope, and subjective reactivity. To examine these questions, 128 young adult alcohol drinkers (ages 18–25) completed questionnaires of alcohol use disorder symptoms, depression symptoms, and drinking to cope with negative affect. Baseline alcohol choice was measured by preference to enlarge alcohol versus food thumbnail images in two-alternative forced-choice trials. Negative mood was then induced by depressive statements and music, before alcohol choice was tested. Subjective reactivity was indexed by increased sadness pre- to post-mood induction. Baseline alcohol choice correlated with alcohol dependence symptoms (p = .001), and drinking coping motives (ps ≤ .01). Mood induction increased alcohol choice and subjective sadness overall (ps < .001). The mood-induced increase in alcohol choice was associated with depression symptoms (p = .007), drinking to cope (ps ≤ .03), and subjective reactivity (p = .007). The relationship between mood-induced alcohol choice and drinking to cope remained significant after covarying for other drinking motives. Furthermore, the three predictors (depression, drinking to cope, and subjective reactivity) accounted for unique variance in mood-induced alcohol choice (ps ≥ .03), and collectively accounted for 18% of the variance (p < .001). These findings validate the pictorial alcohol choice task as sensitive to the relative value of alcohol and acute negative mood. The findings also accord with the core prediction of negative reinforcement theory that sensitivity to the motivational impact of negative mood on alcohol-seeking behavior may be an important mechanism that links depression and alcohol dependence. PMID:29389212

Dispersion relations for electromagnetic wave propagation in chiral plasmas

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

Gao, M. X.; Guo, B., E-mail: binguo@whut.edu.cn; Peng, L.

2014-11-15

The dispersion relations for electromagnetic wave propagation in chiral plasmas are derived using a simplified method and investigated in detail. With the help of the dispersion relations for each eignwave, we explore how the chiral plasmas exhibit negative refraction and investigate the frequency region for negative refraction. The results show that chirality can induce negative refraction in plasmas. Moreover, both the degree of chirality and the external magnetic field have a significant effect on the critical frequency and the bandwidth of the frequency for negative refraction in chiral plasmas. The parameter dependence of the effects is calculated and discussed.

Light tunneling effect tuned by a meta-interface with electromagnetically-induced-transparency-like properties

NASA Astrophysics Data System (ADS)

Feng, Tuanhui; Yang, Fei; Li, Yunhui; Sun, Yong; Lu, Hai; Jiang, Haitao; Zhang, Yewen; Chen, Hong

2013-06-01

In this letter, light tunneling effect tuned by a meta-interface with electromagnetically-induced-transparency-like (EIT-like) properties is investigated. Both numerical and experimental results show that the Q-factor of tunneling mode can be well enhanced when an atomic-like three-level system with EIT-like properties is introduced at the interface of a pair structure constructed by epsilon-negative and mu-negative metamaterials. Further study reveals that the Q-factor can be tuned conveniently by altering the EIT-like meta-interface. Moreover, these advantages are not at costs of increase of volume and drastic reduction of transmittance.

Amphetamine increases schedule-induced drinking reduced by negative punishment procedures.

PubMed

Pérez-Padilla, Angeles; Pellón, Ricardo

2003-05-01

d-Amphetamine has been reported to increase schedule-induced drinking punished by lick-dependent signalled delays in food delivery. This might reflect a drug-behaviour interaction dependent on the type of punisher, because no such effect has been found when drinking was reduced by lick-contingent electric shocks. However, the anti-punishment effect of amphetamine could be mediated by other behavioural processes, such as a loss of discriminative control or an increase in the value of delayed reinforcers. To test the effects of d-amphetamine on the acquisition and maintenance of schedule-induced drinking reduced by unsignalled delays in food delivery. Rats received 10-s unsignalled delays initiated by each lick after polydipsia was induced by a fixed-time 30-s food reinforcement schedule or from the outset of the experiment. Yoked-control rats received these same delays but independently of their own behaviour. d-Amphetamine (0.1-3.0 mg/kg) was then tested IP. d-Amphetamine dose-dependently increased and then decreased punished schedule-induced drinking. The drug led to dose-dependent reductions when the delays were not contingent or when they were applied from the outset of training. These results support the contention that d-amphetamine has an increasing effect on schedule-induced drinking that has been previously reduced by a negative punishment procedure. This effect cannot be attributed to other potentially involved processes, and therefore support the idea that drug effects on punished behaviour depend on punishment being delays in food or shock deliveries.

Strain-induced negative differential resistance in ultrasmall carbon nanotube

NASA Astrophysics Data System (ADS)

Fang, Hui; Zhang, Fei-Peng; Ruan, Xing-Xiang; Huang, Can-Sheng; Jiang, Zhi-Nian; Peng, Jin-Yun; Wang, Ru-Zhi

2017-08-01

The transport properties in ultrasmall single-wall carbon nanotubes (SWCNTs) under tensile strain have been theoretically investigated. The regular negative differential resistance (NDR) induced by the strain undergoes a process from enhancement to weakening in the zigzag (3,0) SWCNT. The NDR achieves maximum with applying 4% tensile strain. Compared to the case of (3,0) SWCNT, that NDR cannot be manipulated by applying strain clearly in (4,0) and (5,0) ultrasmall SWCNTs with tensile strain lower than 10%. It proposes this strain-induced NDR effect to demonstrate the possibility of finding potential applications in SWCNT-based NDR nanodevices such as in memory devices, oscillators and fast switching devices.

Gram-negative, but not Gram-positive, bacteria elicit strong PGE2 production in human monocytes.

PubMed

Hessle, Christina C; Andersson, Bengt; Wold, Agnes E

2003-12-01

Gram-positive and Gram-negative bacteria induce different cytokine patterns in human mononuclear cells. We have seen that Gram-positives preferentially induce IL-12 and TNF-alpha, whereas Gram-negatives induce more IL-10, IL-6, and IL-8. In this study, we compared the capacity of these two groups of bacteria to induce PGE2. Monocytes stimulated with Gram-negative bacterial species induced much more PGE2 than did Gram-positive bacteria (5600 +/- 330 vs. 1700 +/- 670 pg/mL, p < 0.001). Blocking of COX-2 by NS398 abolished PGE2 production, but did not alter the cytokine patterns induced by Gram-positive and Gram-negative bacteria. We suggest that Gram-positive and Gram-negative bacteria may stimulate different innate effector functions; Gram-positive bacteria promoting cell-mediated effector functions whereas Gram-negative bacteria inducing mediators inhibiting the same.

FRNK negatively regulates IL-4-mediated inflammation.

PubMed

Sharma, Ritu; Colarusso, Pina; Zhang, Hong; Stevens, Katarzyna M; Patel, Kamala D

2015-02-15

Focal adhesion kinase (FAK)-related nonkinase (PTK2 isoform 6 in humans, hereafter referred to as FRNK) is a cytoskeletal regulatory protein that has recently been shown to dampen lung fibrosis, yet its role in inflammation is unknown. Here, we show for the first time that expression of FRNK negatively regulates IL-4-mediated inflammation in a human model of eosinophil recruitment. Mechanistically, FRNK blocks eosinophil accumulation, firm adhesion and transmigration by preventing transcription and protein expression of VCAM-1 and CCL26. IL-4 activates STAT6 to induce VCAM-1 and CCL26 transcription. We now show that IL-4 also increases GATA6 to induce VCAM-1 expression. FRNK blocks IL-4-induced GATA6 transcription but has little effect on GATA6 protein expression and no effect on STAT6 activation. FRNK can block FAK or Pyk2 signaling and we, thus, downregulated these proteins using siRNA to determine whether signaling from either protein is involved in the regulation of VCAM-1 and CCL26. Knockdown of FAK, Pyk2 or both had no effect on VCAM-1 or CCL26 expression, which suggests that FRNK acts independently of FAK and Pyk2 signaling. Finally, we found that IL-4 induces the late expression of endogenous FRNK. In summary, FRNK represents a novel mechanism to negatively regulate IL-4-mediated inflammation. © 2015. Published by The Company of Biologists Ltd.

The influence of negative emotion on the Simon effect as reflected by p300.

PubMed

Ma, Qingguo; Shang, Qian

2013-01-01

The Simon effect refers to the phenomenon that reaction time (RT) is faster when stimulus and response location are congruent than when they are not. This study used the priming-target paradigm to explore the influence of induced negative emotion on the Simon effect with event-related potential techniques (ERPs). The priming stimuli were composed of two kinds of pictures, the negative and neutral pictures, selected from the International Affective Picture System (IAPS). The target stimuli included chessboards of two color types. One was red and black the other one was green and black. Each chessboard was presented on the left or the right of the screen. The participants were asked to press the response keys according to the colors of the chessboards. It was called the congruent condition if the chessboard and the response key were on the same side, otherwise incongruent condition. In this study, the emotion-priming Simon effect was found in terms of RT and P300. Negative emotion compared with neutral emotion significantly enhanced the Simon effect in the cognitive process, reflected by a larger difference of P300 latency between the incongruent and congruent trials. The results suggest that the induced negative emotion influenced the Simon effect at the late stage of the cognitive process, and the P300 latency could be considered as the reference measure. These findings may be beneficial to researches in psychology and industrial engineering in the future.

Phase-locked scroll waves defy turbulence induced by negative filament tension.

PubMed

Li, Teng-Chao; Gao, Xiang; Zheng, Fei-Fei; Cai, Mei-Chun; Li, Bing-Wei; Zhang, Hong; Dierckx, Hans

2016-01-01

Scroll waves in a three-dimensional media may develop into turbulence due to negative tension of the filament. Such negative tension-induced instability of scroll waves has been observed in the Belousov-Zhabotinsky reaction systems. Here we propose a method to restabilize scroll wave turbulence caused by negative tension in three-dimensional chemical excitable media using a circularly polarized (rotating) external field. The stabilization mechanism is analyzed in terms of phase-locking caused by the external field, which makes the effective filament tension positive. The phase-locked scroll waves that have positive tension and higher frequency defy the turbulence and finally restore order. A linear theory for the change of filament tension caused by a generic rotating external field is presented and its predictions closely agree with numerical simulations.

ONC201 Demonstrates Antitumor Effects in Both Triple-Negative and Non-Triple-Negative Breast Cancers through TRAIL-Dependent and TRAIL-Independent Mechanisms.

PubMed

Ralff, Marie D; Kline, Christina L B; Küçükkase, Ozan C; Wagner, Jessica; Lim, Bora; Dicker, David T; Prabhu, Varun V; Oster, Wolfgang; El-Deiry, Wafik S

2017-07-01

Breast cancer is a major cause of cancer-related death. TNF-related apoptosis-inducing ligand (TRAIL) has been of interest as a cancer therapeutic, but only a subset of triple-negative breast cancers (TNBC) is sensitive to TRAIL. The small-molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has entered clinical trials in advanced cancers. Here, we show that ONC201 is efficacious against both TNBC and non-TNBC cells ( n = 13). A subset of TNBC and non-TNBC cells succumbs to ONC201-induced cell death. In 2 of 8 TNBC cell lines, ONC201 treatment induces caspase-8 cleavage and cell death that is blocked by TRAIL-neutralizing antibody RIK2. The proapoptotic effect of ONC201 translates to in vivo efficacy in the MDA-MB-468 xenograft model. In most TNBC lines tested (6/8), ONC201 has an antiproliferative effect but does not induce apoptosis. ONC201 decreases cyclin D1 expression and causes an accumulation of cells in the G 1 phase of the cell cycle. pRb expression is associated with sensitivity to the antiproliferative effects of ONC201, and the compound synergizes with taxanes in less sensitive cells. All non-TNBC cells ( n = 5) are growth inhibited following ONC201 treatment, and unlike what has been observed with TRAIL, a subset ( n = 2) shows PARP cleavage. In these cells, cell death induced by ONC201 is TRAIL independent. Our data demonstrate that ONC201 has potent antiproliferative and proapoptotic effects in a broad range of breast cancer subtypes, through TRAIL-dependent and TRAIL-independent mechanisms. These findings develop a preclinical rationale for developing ONC201 as a single agent and/or in combination with approved therapies in breast cancer. Mol Cancer Ther; 16(7); 1290-8. ©2017 AACR . ©2017 American Association for Cancer Research.

Function of the centromedial amygdala in reward devaluation and open-field activity.

PubMed

Kawasaki, K; Glueck, A C; Annicchiarico, I; Papini, M R

2015-09-10

The present research aimed at determining the role played by the amygdala in reward devaluation using transient inactivation induced by lidocaine microinfusions into the centromedial region. Two situations involving reward devaluation were tested in rats: consummatory successive negative contrast (cSNC) and anticipatory negative contrast (ANC). In cSNC, rats exposed to a downshift from 32% to 4% sucrose consume less 4% sucrose than rats always exposed to 4% sucrose. Extensive evidence suggests that reward devaluation in the cSNC situation is accompanied by negative emotion. In ANC, rats consume less 4% sucrose when each session is closely followed by access to 32% sucrose rather than by 4% sucrose. Evidence suggests that reward devaluation in the ANC situation does not involve negative emotions; rather, ANC appears to involve Pavlovian anticipation of the higher value solution. To test the effects of lidocaine microinfusions in a situation known to induce negative emotion, but unrelated to reward devaluation, animals were also exposed to a lighted open field. Centromedial amygdala inactivation reduced the cSNC effect and increased exploratory behavior in the open field, both effects consistent with a reduction in negative emotional state. However, no detectable effects of amygdala inactivation were observed in the ANC situation. These results suggest that, first, the function of the amygdala is not unique to reward devaluation and, second, it is concerned with tagging the devaluation experience with aversive valence. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Negative effect of nanoconfinement on water transport across nanotube membranes

NASA Astrophysics Data System (ADS)

Zhao, Kuiwen; Wu, Huiying; Han, Baosan

2017-10-01

Nanoconfinement environments are commonly considered advantageous for ultrafast water flow across nanotube membranes. This study illustrates that nanoconfinement has a negative effect on water transport across nanotube membranes based on molecular dynamics simulations. Although water viscosity and the friction coefficient evidently decrease because of nanoconfinement, water molecular flux and flow velocity across carbon nanotubes decrease sharply with the pore size of nanotubes. The enhancement of water flow across nanotubes induced by the decreased friction coefficient and water viscosity is markedly less prominent than the negative effect induced by the increased flow barrier as the nanotube size decreases. The decrease in water flow velocity with the pore size of nanotubes indicates that nanoconfinement is not essential for the ultrafast flow phenomenon. In addition, the relationship between flow velocity and water viscosity at different temperatures is investigated at different temperatures. The results indicate that flow velocity is inversely proportional to viscosity for nanotubes with a pore diameter above 1 nm, thereby indicating that viscosity is still an effective parameter for describing the effect of temperature on the fluid transport at the nanoscale.

CSC-3436 switched tamoxifen-induced autophagy to apoptosis through the inhibition of AMPK/mTOR pathway.

PubMed

Wu, Sheng-Tang; Sun, Guang-Huan; Cha, Tai-Lung; Kao, Chien-Chang; Chang, Sun-Yran; Kuo, Sheng-Chu; Way, Tzong-Der

2016-08-15

Triple-negative breast cancer (TNBC) lacks specific therapeutic target and limits to chemotherapy and is essential to develop novel therapeutic regimens. Increasing studies indicated that tamoxifen, a selective estrogen receptor modulators (SERMs), has anti-tumor therapeutic effect in estrogen receptor α (ERα)-negative tumor. Here, we determined whether autophagy was activated by tamoxifen in TNBC cells. Moreover, CSC-3436 displayed strong and selective growth inhibition on cancer cells. Next, we investigated the anti-proliferation effect of combination of CSC-3436 plus tamoxifen on cell death in TNBC cells. Our study found that tamoxifen induces autophagy in TNBC cells. Endoplasmic reticulum stress and AMPK/mTOR contributed tamoxifen-induced autophagy. Interestingly, in combination treatment with CSC-3436 enhanced the anti-proliferative effect of tamoxifen. We found that CSC-3436 switched tamoxifen-induced autophagy to apoptosis via cleavage of ATG-5. Moreover, AMPK/mTOR pathway may involve in CSC-3436 switched tamoxifen-induced autophagy to apoptosis. The combination of tamoxifen and CSC-3436 produced stronger tumor growth inhibition compared with CSC-3436 or tamoxifen alone treatments in vivo. These data indicated that CSC-3436 combined with tamoxifen may be a potential approach for treatment TNBC.

Reactive oxygen species mediate N-(4-hydroxyphenyl)retinamide-induced cell death in malignant T cells and are inhibited by the HTLV-I oncoprotein Tax.

PubMed

Darwiche, N; Abou-Lteif, G; Bazarbachi, A

2007-02-01

N-(4-hydroxyphenyl)retinamide (HPR) is a synthetic retinoid that inhibits growth of many human tumor cells, including those resistant to natural retinoids. HPR is an effective chemopreventive agent for prostate, cervix, breast, bladder, skin and lung cancers, and has shown promise for the treatment of neuroblastomas. We have previously shown that HPR inhibits proliferation and induces apoptosis of human T-cell lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia (ATL) and HTLV-I-negative malignant T cells, whereas no effect is observed on normal lymphocytes. In this report, we identified HPR-induced reactive oxygen species (ROS) generation as the key mediator of cell cycle arrest and apoptosis of malignant T cells. HPR treatment of HTLV-I-negative malignant T cells was associated with a rapid and progressive ROS accumulation. Pre-treatment with the antioxidants vitamin C and dithiothreitol inhibited ROS generation, prevented HPR-induced ceramide accumulation, cell cycle arrest, cytochrome c release, caspase-activation and apoptosis. Therefore, anti-oxidants protected malignant T cells from HPR-induced growth inhibition. The expression of the HTLV-I oncoprotein Tax abrogated HPR-induced ROS accumulation in HTLV-I-infected cells, which explains their lower sensitivity to HPR. Defining the mechanism of free radical induction by HPR may support a potential therapeutic role for this synthetic retinoid in ATL and HTLV-I-negative T-cell lymphomas.

HMBA Enhances Prostratin-Induced Activation of Latent HIV-1 via Suppressing the Expression of Negative Feedback Regulator A20/TNFAIP3 in NF-κB Signaling.

PubMed

Chen, Duchu; Wang, Huiping; Aweya, Jude Juventus; Chen, Yanheng; Chen, Meihua; Wu, Xiaomeng; Chen, Xiaonan; Lu, Jing; Chen, Ruichuan; Liu, Min

2016-01-01

In the past decade, much emphasis has been put on the transcriptional activation of HIV-1, which is proposed as a promised strategy for eradicating latent HIV-1 provirus. Two drugs, prostratin and hexamethylene bisacetamide (HMBA), have shown potent effects as inducers for releasing HIV-1 latency when used alone or in combination, although their cellular target(s) are currently not well understood, especially under drug combination. Here, we have shown that HMBA and prostratin synergistically release HIV-1 latency via different mechanisms. While prostratin strongly stimulates HMBA-induced HIV-1 transcription via improved P-TEFb activation, HMBA is capable of boosting NF-κB-dependent transcription initiation by suppressing prostratin-induced expression of the deubiquitinase A20, a negative feedback regulator in the NF-κB signaling pathway. In addition, HMBA was able to increase prostratin-induced phosphorylation and degradation of NF-κB inhibitor IκBα, thereby enhancing and prolonging prostratin-induced nuclear translocation of NF-κB, a prerequisite for stimulation of transcription initiation. Thus, by blocking the negative feedback circuit, HMBA functions as a signaling enhancer of the NF-κB signaling pathway.

The Prospective Function of Curcumin Against the Negative Effects of Microgravity

NASA Astrophysics Data System (ADS)

Lewis, A.; Johnson, P.; Jejelowo, O. A.; Sodipe, A.; Shishodia, S.

2010-04-01

Microgravity has several deleterious effects on cells. These cells may exhibit an up-regulation or down-regulation of their gene expression. We are investigating the effects of the phytochemical curcumin on microgravity-induced deleterious effects.

Emotion word processing: does mood make a difference?

PubMed

Sereno, Sara C; Scott, Graham G; Yao, Bo; Thaden, Elske J; O'Donnell, Patrick J

2015-01-01

Visual emotion word processing has been in the focus of recent psycholinguistic research. In general, emotion words provoke differential responses in comparison to neutral words. However, words are typically processed within a context rather than in isolation. For instance, how does one's inner emotional state influence the comprehension of emotion words? To address this question, the current study examined lexical decision responses to emotionally positive, negative, and neutral words as a function of induced mood as well as their word frequency. Mood was manipulated by exposing participants to different types of music. Participants were randomly assigned to one of three conditions-no music, positive music, and negative music. Participants' moods were assessed during the experiment to confirm the mood induction manipulation. Reaction time results confirmed prior demonstrations of an interaction between a word's emotionality and its frequency. Results also showed a significant interaction between participant mood and word emotionality. However, the pattern of results was not consistent with mood-congruency effects. Although positive and negative mood facilitated responses overall in comparison to the control group, neither positive nor negative mood appeared to additionally facilitate responses to mood-congruent words. Instead, the pattern of findings seemed to be the consequence of attentional effects arising from induced mood. Positive mood broadens attention to a global level, eliminating the category distinction of positive-negative valence but leaving the high-low arousal dimension intact. In contrast, negative mood narrows attention to a local level, enhancing within-category distinctions, in particular, for negative words, resulting in less effective facilitation.

PHYTOCHROME KINASE SUBSTRATE1 Regulates Root Phototropism and Gravitropism1[C][W][OA

PubMed Central

Boccalandro, Hernán E.; De Simone, Silvia N.; Bergmann-Honsberger, Ariane; Schepens, Isabelle; Fankhauser, Christian; Casal, Jorge J.

2008-01-01

Light promotes the expression of PHYTOCHROME KINASE SUBSTRATE1 (PKS1) in the root of Arabidopsis thaliana, but the function of PKS1 in this organ is unknown. Unilateral blue light induced a negative root phototropic response mediated by phototropin 1 in wild-type seedlings. This response was absent in pks1 mutants. In the wild type, unilateral blue light enhanced PKS1 expression in the subapical region of the root several hours before bending was detectable. The negative phototropism and the enhanced PKS1 expression in response to blue light required phytochrome A (phyA). In addition, the pks1 mutation enhanced the root gravitropic response when vertically oriented seedlings were placed horizontally. The negative regulation of gravitropism by PKS1 occurred even in dark-grown seedlings and did not require phyA. Blue light also failed to induce negative phototropism in pks1 under reduced gravitational stimulation, indicating that the effect of pks1 on phototropism is not simply the consequence of the counteracting effect of enhanced gravitropism. We propose a model where the background level of PKS1 reduces gravitropism. After a phyA-dependent increase in its expression, PKS1 positively affects root phototropism and both effects contribute to negative curvature in response to unilateral blue light. PMID:18024556

PHYTOCHROME KINASE SUBSTRATE1 regulates root phototropism and gravitropism.

PubMed

Boccalandro, Hernán E; De Simone, Silvia N; Bergmann-Honsberger, Ariane; Schepens, Isabelle; Fankhauser, Christian; Casal, Jorge J

2008-01-01

Light promotes the expression of PHYTOCHROME KINASE SUBSTRATE1 (PKS1) in the root of Arabidopsis thaliana, but the function of PKS1 in this organ is unknown. Unilateral blue light induced a negative root phototropic response mediated by phototropin 1 in wild-type seedlings. This response was absent in pks1 mutants. In the wild type, unilateral blue light enhanced PKS1 expression in the subapical region of the root several hours before bending was detectable. The negative phototropism and the enhanced PKS1 expression in response to blue light required phytochrome A (phyA). In addition, the pks1 mutation enhanced the root gravitropic response when vertically oriented seedlings were placed horizontally. The negative regulation of gravitropism by PKS1 occurred even in dark-grown seedlings and did not require phyA. Blue light also failed to induce negative phototropism in pks1 under reduced gravitational stimulation, indicating that the effect of pks1 on phototropism is not simply the consequence of the counteracting effect of enhanced gravitropism. We propose a model where the background level of PKS1 reduces gravitropism. After a phyA-dependent increase in its expression, PKS1 positively affects root phototropism and both effects contribute to negative curvature in response to unilateral blue light.

Positive and negative affect produce opposing task-irrelevant stimulus preexposure effects.

PubMed

Lazar, Josef; Kaplan, Oren; Sternberg, Terri; Lubow, R E

2012-06-01

In three experiments, groups were exposed to either positive or negative affect video clips, after which they were presented with a series of task-irrelevant stimuli. In the subsequent test task, subjects were required to learn an association between the previously irrelevant stimulus and a consequence, and between a new stimulus and a consequence. Induced positive affect produced a latent inhibition effect (poorer evidence of learning with the previously irrelevant stimulus than with the novel stimulus). In opposition to this, induced negative affect resulted in better evidence of learning with a previously irrelevant stimulus than with a novel stimulus. In general, the opposing effects also were present in participants scoring high on self-report questionnaires of depression (Experiments 2 and 3). These unique findings were predicted and accounted for on the basis of two principles: (a) positive affect broadens the attentional field and negative affect contracts it; and (b) task-irrelevant stimuli are processed in two successive stages, the first encodes stimulus properties, and the second encodes stimulus relationships. The opposing influences of negative and positive mood on the processing of irrelevant stimuli have implications for the role of emotion in general theories of cognition, and possibly for resolving some of the inconsistent findings in research with schizophrenia patients.

Gender‐specific effects of comorbid depression and anxiety on the propensity to drink in negative emotional states

PubMed Central

Biernacka, Joanna M.; Geske, Jennifer R.; Abulseoud, Osama A.; Brunner, Michael D.; Chauhan, Mohit; Hall‐Flavin, Daniel K.; Lewis, Kriste A.; Loukianova, Larissa L.; Melnyk, George J.; Onsrud, David A.; Proctor, Brian D.; Schneekloth, Terry D.; Skime, Michelle K.; Wittkopp, John E.; Frye, Mark A.; Mrazek, David A.

2016-01-01

Abstract Background and Aims Depression and anxiety are often comorbid with alcoholism and contribute to craving and relapse. We aimed to estimate the prevalence of life‐time diagnoses of major depressive disorder (MDD), substance‐induced depression (SID), anxiety disorder (AnxD) and substance‐induced anxiety (SIA), the effects of these comorbidities on the propensity to drink in negative emotional states (negative craving), and test whether these effects differ by sex. Design Secondary analyses of baseline data collected in a single‐arm study of pharmacogenetic predictors of acamprosate response. Setting Academic medical center and affiliated community‐based treatment programs in the American upper mid‐west. Participants A total of 287 males and 156 females aged 18–80 years, meeting DSM‐IV criteria for alcohol dependence. Measurements The primary outcome measure was ‘propensity to drink in negative emotional situations’ (determined by the Inventory of Drug Taking Situations) and the key predictors/covariates were sex and psychiatric comorbidities, including MDD, SID, AnxD and SIA (determined by Psychiatric Research Interview of Substance and Mood Disorders). Findings The prevalence of the MDD, SID and AnxD was higher in females compared with males (33.1 versus 18.4%, 44.8 versus 26.4% and 42.2 versus 27.4%, respectively; P < 0.01, each), while SIA was rare (3.3%) and did not differ by sex. Increased propensity to drink in negative emotional situations was associated with comorbid MDD (β = 6.6, P = 0.013) and AnxD (β = 4.8, P = 0.042) as well as a SID × sex interaction effect (P = 0.003), indicating that the association of SID with propensity to drink in negative emotional situations differs by sex and is stronger in males (β = 7.9, P = 0.009) compared with females (β = −6.6, P = 0.091). Conclusions There appears to be a higher prevalence of comorbid depression and anxiety disorders as well as propensity to drink in negative emotional situations in female compared with male alcoholics. Substance‐induced depression appears to have a sex‐specific effect on the increased risk for drinking in negative emotional situations in males. PMID:27009547

Gender-specific effects of comorbid depression and anxiety on the propensity to drink in negative emotional states.

PubMed

Karpyak, Victor M; Biernacka, Joanna M; Geske, Jennifer R; Abulseoud, Osama A; Brunner, Michael D; Chauhan, Mohit; Hall-Flavin, Daniel K; Lewis, Kriste A; Loukianova, Larissa L; Melnyk, George J; Onsrud, David A; Proctor, Brian D; Schneekloth, Terry D; Skime, Michelle K; Wittkopp, John E; Frye, Mark A; Mrazek, David A

2016-08-01

Depression and anxiety are often comorbid with alcoholism and contribute to craving and relapse. We aimed to estimate the prevalence of life-time diagnoses of major depressive disorder (MDD), substance-induced depression (SID), anxiety disorder (AnxD) and substance-induced anxiety (SIA), the effects of these comorbidities on the propensity to drink in negative emotional states (negative craving), and test whether these effects differ by sex. Secondary analyses of baseline data collected in a single-arm study of pharmacogenetic predictors of acamprosate response. Academic medical center and affiliated community-based treatment programs in the American upper mid-west. A total of 287 males and 156 females aged 18-80 years, meeting DSM-IV criteria for alcohol dependence. The primary outcome measure was 'propensity to drink in negative emotional situations' (determined by the Inventory of Drug Taking Situations) and the key predictors/covariates were sex and psychiatric comorbidities, including MDD, SID, AnxD and SIA (determined by Psychiatric Research Interview of Substance and Mood Disorders). The prevalence of the MDD, SID and AnxD was higher in females compared with males (33.1 versus 18.4%, 44.8 versus 26.4% and 42.2 versus 27.4%, respectively; P < 0.01, each), while SIA was rare (3.3%) and did not differ by sex. Increased propensity to drink in negative emotional situations was associated with comorbid MDD (β = 6.6, P = 0.013) and AnxD (β = 4.8, P = 0.042) as well as a SID × sex interaction effect (P = 0.003), indicating that the association of SID with propensity to drink in negative emotional situations differs by sex and is stronger in males (β = 7.9, P = 0.009) compared with females (β = -6.6, P = 0.091). There appears to be a higher prevalence of comorbid depression and anxiety disorders as well as propensity to drink in negative emotional situations in female compared with male alcoholics. Substance-induced depression appears to have a sex-specific effect on the increased risk for drinking in negative emotional situations in males. © 2016 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

[Protective effect of Helianthus annuus (sunflower) on myocardial infarction in New Zealand rabbit].

PubMed

Guardia-Espinoza, Edith; Herrera-Hurtado, Gianina Liseth del Carmen; Garrido-Jacobi, Saúl; Cárdenas-Peralta, Danitza; Martínez-Romero, Christian; Hernández-Figueroa, Pedro; Condori-Calizaya, Mary; La Barrera-Llacchua, Juan; Flores-Ángeles, Miguel

2015-01-01

Determine the protective effect of oil Helianthus annuus (Sunflower) on myocardial infarction induced by epinephrine in New Zealand rabbits. The rabbits were randomized into five groups (8 per group): blank, negative control, experimental 1 (10 mg / kg), experimental 2 (20 mg / kg) and three experimental (40 mg/ kg). Experimental groups 1, 2 and 3 received Helianthus annuus oil for two weeks. Epinephrine (2 mg/Kg) to the negative, Experimental Control 1, 2 and 3 groups was given over two consecutive days with an interval of 24 h after pretreatment with oil. Twenty four hours after the last administration, the rabbits were anesthetized and sacrificed. Serum troponin I and polymorphonuclear evaluated by .mu.m.sup.2. Significant difference between the negative control group and the experimental groups 1, 2 and 3 was found in the serum variables troponin I and polymorphonuclear by .mu.m.sup.2. Helianthus annuus oil at doses of 20 mg/kg has protective effect on myocardial infarction induced by epinephrine in New Zealand rabbits.

Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers.

PubMed

Kraehenmann, Rainer; Preller, Katrin H; Scheidegger, Milan; Pokorny, Thomas; Bosch, Oliver G; Seifritz, Erich; Vollenweider, Franz X

2015-10-15

The amygdala is a key structure in serotonergic emotion-processing circuits. In healthy volunteers, acute administration of the serotonin 1A/2A/2C receptor agonist psilocybin reduces neural responses to negative stimuli and induces mood changes toward positive states. However, it is little-known whether psilocybin reduces amygdala reactivity to negative stimuli and whether any change in amygdala reactivity is related to mood change. This study assessed the effects of acute administration of the hallucinogen psilocybin (.16 mg/kg) versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers using blood oxygen level-dependent functional magnetic resonance imaging. Mood changes were assessed using the Positive and Negative Affect Schedule and the state portion of the State-Trait Anxiety Inventory. A double-blind, randomized, cross-over design was used with volunteers counterbalanced to receive psilocybin and placebo in two separate sessions at least 14 days apart. Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration. The psilocybin-induced attenuation of right amygdala reactivity in response to negative stimuli was related to the psilocybin-induced increase in positive mood state. These results demonstrate that acute treatment with psilocybin decreased amygdala reactivity during emotion processing and that this was associated with an increase of positive mood in healthy volunteers. These findings may be relevant to the normalization of amygdala hyperactivity and negative mood states in patients with major depression. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

On the search for the chiral anomaly in Weyl semimetals: the negative longitudinal magnetoresistance

NASA Astrophysics Data System (ADS)

dos Reis, R. D.; Ajeesh, M. O.; Kumar, N.; Arnold, F.; Shekhar, C.; Naumann, M.; Schmidt, M.; Nicklas, M.; Hassinger, E.

2016-08-01

Recently, the existence of massless chiral (Weyl) fermions has been postulated in a class of semi-metals with a non-trivial energy dispersion. These materials are now commonly dubbed Weyl semi-metals (WSM). One predicted property of Weyl fermions is the chiral or Adler-Bell-Jackiw anomaly, a chirality imbalance in the presence of parallel magnetic and electric fields. In WSM, it is expected to induce a negative longitudinal magnetoresistance (MR). Here, we present experimental evidence that the observation of the chiral anomaly can be hindered by an effect called ‘current jetting’. This effect also leads to a strong apparent negative longitudinal MR, but it is characterized by a highly non-uniform current distribution inside the sample. It appears in materials possessing a large field-induced anisotropy of the resistivity tensor, such as almost compensated high-mobility semimetals due to the orbital effect. In case of a non-homogeneous current injection, the potential distribution is strongly distorted in the sample. As a consequence, an experimentally measured potential difference is not proportional to the intrinsic resistance. Our results on the MR of the Weyl semimetal candidate materials NbP, NbAs, TaAs, and TaP exhibit distinct signatures of an inhomogeneous current distribution, such as a field-induced ‘zero resistance’ and a strong dependence of the ‘measured resistance’ on the position, shape, and type of the voltage and current contacts on the sample. A misalignment between the current and the magnetic-field directions can even induce a ‘negative resistance’. Finite-element simulations of the potential distribution inside the sample, using typical resistance anisotropies, are in good agreement with the experimental findings. Our study demonstrates that great care must be taken before interpreting measurements of a negative longitudinal MR as evidence for the chiral anomaly in putative Weyl semimetals.

Cognitive Bias Modification Training in Adolescents: Effects on Interpretation Biases and Mood

ERIC Educational Resources Information Center

Lothmann, Claudia; Holmes, Emily A.; Chan, Stella W. Y.; Lau, Jennifer Y. F.

2011-01-01

Background: Negative biases in the interpretation of ambiguous material have been linked to anxiety and mood problems. Accumulating data from adults show that positive and negative interpretation styles can be induced through cognitive bias modification (CBM) paradigms with accompanying changes in mood. Despite the therapeutic potential of…

Alcohol-induced physiological displacements and their effects on flight-related functions.

DOT National Transportation Integrated Search

1982-03-01

Tolerances of human subjects for orthostasis and physical work were determined at a simulated altitude of 3,048 m. Orthostasis was induced with a lower body negative pressure (LBNP) device and physical work was done on a pedal ergometer. Altitude was...

The Effect of Metal-Semiconductor Contact on the Transient Photovoltaic Characteristic of HgCdTe PV Detector

PubMed Central

Cui, Haoyang; Xu, Yongpeng; Yang, Junjie; Tang, Naiyun; Tang, Zhong

2013-01-01

The transient photovoltaic (PV) characteristic of HgCdTe PV array is studied using an ultrafast laser. The photoresponse shows an apparent negative valley first, then it evolves into a positive peak. By employing a combined theoretical model of pn junction and Schottky potential, this photo-response polarity changing curves can be interpreted well. An obvious decreasing of ratio of negative valley to positive peak can be realized by limiting the illumination area of the array electrode. This shows that the photoelectric effect of Schottky barrier at metal-semiconductor (M/S) interface is suppressed, which will verify the correctness of the model. The characteristic parameters of transient photo-response induced from p-n junction and Schottky potential are extracted by fitting the response curve utilizing this model. It shows that the negative PV response induced by the Schottky barrier decreases the positive photovoltage generated by the pn junction. PMID:24194676

Effects of Cable News Watching on Older Adults' Physiological and Self-Reported Stress and Cognitive Function.

PubMed

Deal, Caroline; Bogdan, Ryan; Miller, J Phil; Rodebaugh, Tom; Caburnay, Charlene; Yingling, Mike; Hershey, Tammy; Schweiger, Julia; Lenze, Eric J

2017-01-01

Older adults are the largest consumer of cable news, which includes negative and politicized content and may constitute a daily stressor. As older adults are also vulnerable to the negative consequences of stress, we hypothesized that cable news watching could induce a stress reaction and impair cognitive function. We tested exposures to cable news (i.e., Fox News and MSNBC) in a within-subject randomized controlled design in 34 healthy older adults. We also included negative (Public Broadcasting Station) and positive (trier social stress test) controls. Cable news watching had no effect on psychological stress, physiological stress, or cognitive function. This remained true even if the news exposures were discordant with participants' political affiliation. We conclude that brief cable news watching does not induce a physiological or subjective stress response or cognitive impairment among healthy older adults.

The effect of metal-semiconductor contact on the transient photovoltaic characteristic of HgCdTe PV detector.

PubMed

Cui, Haoyang; Xu, Yongpeng; Yang, Junjie; Tang, Naiyun; Tang, Zhong

2013-01-01

The transient photovoltaic (PV) characteristic of HgCdTe PV array is studied using an ultrafast laser. The photoresponse shows an apparent negative valley first, then it evolves into a positive peak. By employing a combined theoretical model of pn junction and Schottky potential, this photo-response polarity changing curves can be interpreted well. An obvious decreasing of ratio of negative valley to positive peak can be realized by limiting the illumination area of the array electrode. This shows that the photoelectric effect of Schottky barrier at metal-semiconductor (M/S) interface is suppressed, which will verify the correctness of the model. The characteristic parameters of transient photo-response induced from p-n junction and Schottky potential are extracted by fitting the response curve utilizing this model. It shows that the negative PV response induced by the Schottky barrier decreases the positive photovoltage generated by the pn junction.

PCP-induced deficits in murine nest building activity: employment of an ethological rodent behavior to mimic negative-like symptoms of schizophrenia.

PubMed

Pedersen, Christian Spang; Sørensen, Dorte Bratbo; Parachikova, Anna I; Plath, Niels

2014-10-15

Schizophrenia is a severe psychiatric disorder characterized by three symptom domains, positive (hallucinations, obsession), negative (social withdrawal, apathy, self-neglect) and cognitive (impairment in attention, memory and executive function). Whereas current medication ameliorates positive symptomatology, negative symptoms as well as cognitive dysfunctions remain untreated. The development of improved therapies for negative symptoms has proven particularly difficult, in part due to the inability of mimicking these in rodents. Here, we address the predictive validity of combining an ethologically well preserved behavior in rodents, namely nest building activity, with an established animal model of schizophrenia, the sub-chronic PCP model, for negative symptoms. Decline in rodent nesting activity has been suggested to mirror domains of negative symptoms of schizophrenia, including social withdrawal, anhedonia and self-neglect, whereas repeated treatment with the NMDAR antagonist PCP induces and exacerbates schizophrenia-like symptoms in rodents and human subjects. Using a back-translational approach of pharmacological validation, we tested the effects of two agents targeting the nicotinic α7 receptor (EVP-6124 and TC-5619) that were reported to exert some beneficial effect on negative symptoms in schizophrenic patients. Sub-chronic PCP treatment resulted in a significant nest building deficit in mice and treatment with EVP-6124 and TC-5619 reversed this PCP-induced deficit. In contrast, the atypical antipsychotic drug risperidone remained ineffective in this assay. In addition, EVP-6124, TC-5619 and risperidone were tested in the Social Interaction Test (SIT), an assay suggested to address negative-like symptoms. Results obtained in SIT were comparable to results in the nest building test (NEST). Based on these findings, we propose nest building in combination with the sub-chronic PCP model as a novel approach to assess negative-like symptoms of schizophrenia in rodents. Copyright © 2014 Elsevier B.V. All rights reserved.

Calcium ion involvement in growth inhibition of mechanically stressed soybean (Glycine max) seedlings

NASA Technical Reports Server (NTRS)

Jones, R. S.; Mitchell, C. A.

1989-01-01

A 40-50% reduction in soybean [Glycine max (L.) Merr. cv. Century 84] hypocotyl elongation occurred 24 h after application of mechanical stress. Exogenous Ca2+ at 10 mM inhibited growth by 28% if applied with the Ca2+ ionophore A23187 to the zone of maximum hypocotyl elongation. La3+ was even more inhibitory than Ca2+, especially above 5 mM. Treatment with ethyleneglycol-bis-(beta-aminoethylether)-N, N, N', N'-tetraacetic acid (EGTA) alone had no effect on growth of non-stressed seedlings at the concentrations used but negated stress-induced growth reduction by 36% at 4 mM when compared to non-treated, stressed controls. Treatment with EDTA was ineffective in negating stress-induced growth inhibition. Calmodulin antagonists calmidazolium, chlorpromazine, and 48/80 also negated stress-induced growth reduction by 23, 50, and 35%, respectively.

Investigations on caesium-free alternatives for H{sup −} formation at ion source relevant parameters

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

Kurutz, U.; Fantz, U.; AG Experimentelle Plasmaphysik, Institut für Physik, Universität Augsburg, 86135 Augsburg

2015-04-08

Negative hydrogen ions are efficiently produced in ion sources by the application of caesium. Due to a thereby induced lowering of the work function of a converter surface a direct conversion of impinging hydrogen atoms and positive ions into negative ions is maintained. However, due to the complex caesium chemistry and dynamics a long-term behaviour is inherent for the application of caesium that affects the stability and reliability of negative ion sources. To overcome these drawbacks caesium-free alternatives for efficient negative ion formation are investigated at the flexible laboratory setup HOMER (HOMogenous Electron cyclotron Resonance plasma). By the usage ofmore » a meshed grid the tandem principle is applied allowing for investigations on material induced negative ion formation under plasma parameters relevant for ion source operation. The effect of different sample materials on the ratio of the negative ion density to the electron density n{sub H{sup −}} /n{sub e} is compared to the effect of a stainless steel reference sample and investigated by means of laser photodetachment in a pressure range from 0.3 to 3 Pa. For the stainless steel sample no surface induced effect on the negative ion density is present and the measured negative ion densities are resulting from pure volume formation and destruction processes. In a first step the dependency of n{sub H{sup −}} /n{sub e} on the sample distance has been investigated for a caesiated stainless steel sample. At a distance of 0.5 cm at 0.3 Pa the density ratio is 3 times enhanced compared to the reference sample confirming the surface production of negative ions. In contrast for the caesium-free material samples, tantalum and tungsten, the same dependency on pressure and distance n{sub H{sup −}} /n{sub e} like for the stainless steel reference sample were obtained within the error margins: A density ratio of around 14.5% is measured at 4.5 cm sample distance and 0.3 Pa, linearly decreasing with decreasing distance to 7% at 1.5 cm. Thus, tantalum and tungsten do not significantly affect the negative ion density. First measurements conducted with LaB{sub 6} as well as with two types of diamond like carbon (DLC) n{sub H{sup −}} /n{sub e} of about 15% at 1 Pa were measured, which is comparable to the density ratio obtained for the stainless steel reference sample. At HOMER a surface induced enhancement of n{sub H{sup −}} is only observed when it exceeds the volume formation of H{sup −} which is also realistic for negative hydrogen ion sources.« less

Stimulation of the metabotropic glutamate (mGlu) 2 receptor attenuates the MK-801-induced increase in the immobility time in the forced swimming test in rats.

PubMed

Kawaura, Kazuaki; Karasawa, Jun-Ichi; Hikichi, Hirohiko

2016-02-01

Negative symptoms of schizophrenia are poorly managed using the currently available antipsychotics. Previous studies indicate that agonists of the metabotropic glutamate (mGlu) 2/3 receptors may provide a novel approach for the treatment of schizophrenia. However, the effects of mGlu2/3 receptor agonists or mGlu2 receptor positive allosteric modulators have not yet been clearly elucidated in animal models of the negative symptoms of schizophrenia. Recently, we reported that the forced swimming test in rats treated with subchronic MK-801, an NMDA receptor antagonist, may be regarded as a useful test to evaluate the activities of drugs against the negative symptoms of schizophrenia. We evaluated the effects of LY379268, an mGlu2/3 receptor agonist, and BINA, an mGlu2 receptor positive allosteric modulator, on the hyperlocomotion induced by acute administration of MK-801 (0.15mg/kg, sc) and on the increase in the immobility time in the forced swimming test induced by subchronic treatment with MK-801 (0.5mg/kg, sc, twice a day for 7 days) in rats. Both LY379268 (3mg/kg, sc) and BINA (100mg/kg, ip) attenuated the increase in the immobility time induced by subchronic treatment with MK-801 at the same doses at which they attenuated the MK-801-induced increase in locomotor activity, but had no effect on the immobility time in saline-treated rats. The present results suggest that stimulation of the mGlu2 receptor attenuates the increase in the immobility time in the forced swimming test elicited by subchronic administration of MK-801, and may be potentially useful for treatment of the negative symptoms of schizophrenia. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Effectiveness of internet-based affect induction procedures: A systematic review and meta-analysis.

PubMed

Ferrer, Rebecca A; Grenen, Emily G; Taber, Jennifer M

2015-12-01

Procedures used to induce affect in a laboratory are effective and well-validated. Given recent methodological and technological advances in Internet research, it is important to determine whether affect can be effectively induced using Internet methodology. We conducted a meta-analysis and systematic review of prior research that has used Internet-based affect induction procedures, and examined potential moderators of the effectiveness of affect induction procedures. Twenty-six studies were included in final analyses, with 89 independent effect sizes. Affect induction procedures effectively induced general positive affect, general negative affect, fear, disgust, anger, sadness, and guilt, but did not significantly induce happiness. Contamination of other nontarget affect did not appear to be a major concern. Video inductions resulted in greater effect sizes. Overall, results indicate that affect can be effectively induced in Internet studies, suggesting an important venue for the acceleration of affective science. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Preliminary Support for a Generalized Arousal Model of Political Conservatism

PubMed Central

Tritt, Shona M.; Inzlicht, Michael; Peterson, Jordan B.

2013-01-01

It is widely held that negative emotions such as threat, anxiety, and disgust represent the core psychological factors that enhance conservative political beliefs. We put forward an alternative hypothesis: that conservatism is fundamentally motivated by arousal, and that, in this context, the effect of negative emotion is due to engaging intensely arousing states. Here we show that study participants agreed more with right but not left-wing political speeches after being exposed to positive as well as negative emotion-inducing film-clips. No such effect emerged for neutral-content videos. A follow-up study replicated and extended this effect. These results are consistent with the idea that emotional arousal, in general, and not negative valence, specifically, may underlie political conservatism. PMID:24376687

Superlensing effect for surface acoustic waves in a pillar-based phononic crystal with negative refractive index

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

Addouche, Mahmoud, E-mail: mamoud.addouche@femto-st.fr; Al-Lethawe, Mohammed A., E-mail: mohammed.abdulridha@femto-st.fr; Choujaa, Abdelkrim, E-mail: achoujaa@femto-st.fr

2014-07-14

We demonstrate super resolution imaging for surface acoustic waves using a phononic structure displaying negative refractive index. This phononic structure is made of a monolithic square lattice of cylindrical pillars standing on a semi-infinite medium. The pillars act as acoustic resonator and induce a surface propagating wave with unusual dispersion. We found, under specific geometrical parameters, one propagating mode that exhibits negative refraction effect with negative effective index close to −1. Furthermore, a flat lens with finite number of pillars is designed to allow the focusing of an acoustic point source into an image with a resolution of (λ)/3 ,more » overcoming the Rayleigh diffraction limit.« less

Preliminary support for a generalized arousal model of political conservatism.

PubMed

Tritt, Shona M; Inzlicht, Michael; Peterson, Jordan B

2013-01-01

It is widely held that negative emotions such as threat, anxiety, and disgust represent the core psychological factors that enhance conservative political beliefs. We put forward an alternative hypothesis: that conservatism is fundamentally motivated by arousal, and that, in this context, the effect of negative emotion is due to engaging intensely arousing states. Here we show that study participants agreed more with right but not left-wing political speeches after being exposed to positive as well as negative emotion-inducing film-clips. No such effect emerged for neutral-content videos. A follow-up study replicated and extended this effect. These results are consistent with the idea that emotional arousal, in general, and not negative valence, specifically, may underlie political conservatism.

Joint effects of emotion and color on memory.

PubMed

Kuhbandner, Christof; Pekrun, Reinhard

2013-06-01

Numerous studies have shown that memory is enhanced for emotionally negative and positive information relative to neutral information. We examined whether emotion-induced memory enhancement is influenced by low-level perceptual attributes such as color. Because in everyday life red is often used as a warning signal, whereas green signals security, we hypothesized that red might enhance memory for negative information and green memory for positive information. To capture the signaling function of colors, we measured memory for words standing out from the context by color, and manipulated the color and emotional significance of the outstanding words. Making words outstanding by color strongly enhanced memory, replicating the well-known von Restorff effect. Furthermore, memory for colored words was further increased by emotional significance, replicating the memory-enhancing effect of emotion. Most intriguingly, the effects of emotion on memory additionally depended on color type. Red strongly increased memory for negative words, whereas green strongly increased memory for positive words. These findings provide the first evidence that emotion-induced memory enhancement is influenced by color and demonstrate that different colors can have different functions in human memory.

Steroid-induced hypocalcaemia with tetany in a patient with hypoparathyroidism.

PubMed

Oikonomou, Dimitrios; Laina, Ageliki; Xydaki, Aikaterini; Christopoulos, Constantinos

2014-11-18

Although glucocorticoids have a known negative effect on calcium balance, they do not normally cause clinically significant hypocalcaemia. A young woman with post-surgical hypoparathyroidism developed symptomatic hypocalcaemia on two occasions following treatment with intravenous hydrocortisone for allergic reactions. Oral calcium and vitamin D supplementation could not prevent the development of hypocalcaemia. She was treated successfully with intravenous calcium gluconate infusions and discontinuation of glucocorticoids. In patients with hypoparathyroidism, impaired parathyroid hormone response to steroid-induced negative calcium balance may result in severe symptomatic hypocalcaemia requiring hospitalisation. 2014 BMJ Publishing Group Ltd.

Steroid-induced hypocalcaemia with tetany in a patient with hypoparathyroidism

PubMed Central

Oikonomou, Dimitrios; Laina, Ageliki; Xydaki, Aikaterini; Christopoulos, Constantinos

2014-01-01

Although glucocorticoids have a known negative effect on calcium balance, they do not normally cause clinically significant hypocalcaemia. A young woman with post-surgical hypoparathyroidism developed symptomatic hypocalcaemia on two occasions following treatment with intravenous hydrocortisone for allergic reactions. Oral calcium and vitamin D supplementation could not prevent the development of hypocalcaemia. She was treated successfully with intravenous calcium gluconate infusions and discontinuation of glucocorticoids. In patients with hypoparathyroidism, impaired parathyroid hormone response to steroid-induced negative calcium balance may result in severe symptomatic hypocalcaemia requiring hospitalisation. PMID:25406219

Drama-induced affect and pain sensitivity.

PubMed

Zillmann, D; de Wied, M; King-Jablonski, C; Jenzowsky, S

1996-01-01

This study was conducted to examine the pain-ameliorating and pain-sensitizing effects of exposure to emotionally engaging drama. Specifically, the consequences for pain sensitivity of exposure to dramatic expositions differing in both excitatory and hedonic qualities were determined. Hedonically negative, neutral, and positive affective states were induced in male respondents by exposure to excerpts from cinematic drama. Pain sensitivity was assessed by the cuff-pressure procedure before and after exposure and by the cold pressor test after exposure only. When compared against the control condition, pain sensitivity diminished under conditions of hedonically positive affect. An inverse effect was suggested for hedonically negative conditions, but proved tentative and statistically unreliable. The findings are consistent with earlier demonstrations of mood effects on pain sensitivity. Unlike inconclusive earlier findings concerning the magnitude of directional effects, however, they suggest an asymmetry that emphasizes the pain-ameliorating effect of positive affects while lending little, if any, support to the proposal of a pain-sensitizing effect of negative affects. The investigation did not accomplish the intended creation of conditions necessary to test the proposal that heightened sympathetic activity diminishes pain sensitivity. The utility of a rigorous determination of this hypothesized relationship is emphasized, and procedures for a viable test of the proposal are suggested.

Steep-slope hysteresis-free negative capacitance MoS2 transistors

NASA Astrophysics Data System (ADS)

Si, Mengwei; Su, Chun-Jung; Jiang, Chunsheng; Conrad, Nathan J.; Zhou, Hong; Maize, Kerry D.; Qiu, Gang; Wu, Chien-Ting; Shakouri, Ali; Alam, Muhammad A.; Ye, Peide D.

2018-01-01

The so-called Boltzmann tyranny defines the fundamental thermionic limit of the subthreshold slope of a metal-oxide-semiconductor field-effect transistor (MOSFET) at 60 mV dec-1 at room temperature and therefore precludes lowering of the supply voltage and overall power consumption1,2. Adding a ferroelectric negative capacitor to the gate stack of a MOSFET may offer a promising solution to bypassing this fundamental barrier3. Meanwhile, two-dimensional semiconductors such as atomically thin transition-metal dichalcogenides, due to their low dielectric constant and ease of integration into a junctionless transistor topology, offer enhanced electrostatic control of the channel4-12. Here, we combine these two advantages and demonstrate a molybdenum disulfide (MoS2) two-dimensional steep-slope transistor with a ferroelectric hafnium zirconium oxide layer in the gate dielectric stack. This device exhibits excellent performance in both on and off states, with a maximum drain current of 510 μA μm-1 and a sub-thermionic subthreshold slope, and is essentially hysteresis-free. Negative differential resistance was observed at room temperature in the MoS2 negative-capacitance FETs as the result of negative capacitance due to the negative drain-induced barrier lowering. A high on-current-induced self-heating effect was also observed and studied.

Five-year lidar observational results and effects of El Chichon particles on Umkehr ozone data

NASA Astrophysics Data System (ADS)

Uchino, Osamu; Tabata, Isao; Kai, Kenji; Akita, Iwao

1988-08-01

Based on the values of integrated backscattering coefficient B, obtained from the ruby lidar measurements at the Meteorological Research Institude (MRI, at Tsukuba, Japan), the effect of dust particles due to two volcanic eruptions of Mt. El Chichon in 1982 on the Umkehr ozone data at the Tateno Aerological Observatory was determined. In addition, the effects of the aerosols on the Umkehr ozone data at Arosa, Switzerland were investigated using lidar data collected at Garmisch-Partenkirchen, Germany. It was found that both stratospheric and tropospheric aerosols induced a significant negative ozone error in the uppermost layers (33-47 km), caused a small and usually negative ozone error in layers between 16 and 33 km, and induced a significant positive ozone error in layers between 6 and 16 km.

Mechanism of protection of transepithelial barrier function by Lactobacillus salivarius: strain dependence and attenuation by bacteriocin production.

PubMed

Miyauchi, Eiji; O'Callaghan, John; Buttó, Ludovica F; Hurley, Gráinne; Melgar, Silvia; Tanabe, Soichi; Shanahan, Fergus; Nally, Kenneth; O'Toole, Paul W

2012-11-01

Enhanced barrier function is one mechanism whereby commensals and probiotic bacteria limit translocation of foreign antigens or pathogens in the gut. However, barrier protection is not exhibited by all probiotic or commensals and the strain-specific molecules involved remain to be clarified. We evaluated the effects of 33 individual Lactobacillus salivarius strains on the hydrogen peroxide (H(2)O(2))-induced barrier impairment in human epithelial Caco-2 cells. These strains showed markedly different effects on H(2)O(2)-induced reduction in transepithelial resistance (TER). The effective strains such as UCC118 and CCUG38008 attenuated H(2)O(2)-induced disassembly and relocalization of tight junction proteins, but the ineffective strain AH43324 did not. Strains UCC118 and CCUG38008 induced phosphorylation of extracellular signal-regulated kinase (ERK) in Caco-2 cells, and the ERK inhibitor U0126 attenuated the barrier-protecting effect of these strains. In contrast, the AH43324 strain induced phosphorylation of Akt and p38, which was associated with an absence of a protective effect. Global transcriptome analysis of UCC118 and AH43324 revealed that some genes in a bacteriocin gene cluster were upregulated in AH43324 under TER assay conditions. A bacteriocin-negative UCC118 mutant displayed significantly greater suppressive effect on H(2)O(2)-induced reduction in TER compared with wild-type UCC118. The wild-type strain augmented H(2)O(2)-induced phosphorylation of Akt and p38, whereas a bacteriocin-negative UCC118 mutant did not. These observations indicate that L. salivarius strains are widely divergent in their capacity for barrier protection, and this is underpinned by differences in the activation of intracellular signaling pathways. Furthermore, bacteriocin production appears to have an attenuating influence on lactobacillus-mediated barrier protection.

Disentangling opposing effects of motivational states on pain perception

PubMed Central

Geuter, Stephan; Cunningham, Jonathan T.; Wager, Tor D.

2016-01-01

Abstract Introduction: Although the motivation to avoid injury and pain is central to human and animal behavior, this goal compete priority with other homeostatic goals. Animal studies have shown that competing motivational states, such as thirst, reduce pain. However, such states may also induce negative mood, which in humans has been found to increase pain. These opposing effects complicate study of the effects of motivational states in humans. Objectives: To evaluate concurrent effects of motivational state competition and mood on pain ratings. Methods: We compared a thirst challenge against a control group and measured thirst and mood as potential mediators. Pain induced through contact heat stimulation on the left forearm and was tested at 3 time points: before group randomization, after thirst induction, and after rehydration. Results: Overall, the thirst group reported more pain when thirsty compared with baseline and controls. Mediation analyses showed evidence for two opposing effects. First, the thirst challenge increased negative mood and thirstiness, which was related to increased pain. Second, the thirst challenge produced a direct, pain-reducing effect. Conclusion: Competing motivational states reduce pain but also induce concurrent mood changes that can mask motivational state-related effects. PMID:27747310

Negative Self-Focused Cognitions Mediate the Effect of Trait Social Anxiety on State Anxiety

PubMed Central

Schulz, Stefan M.; Alpers, Georg W.; Hofmann, Stefan G.

2008-01-01

The cognitive model of social anxiety predicts that negative self-focused cognitions increase anxiety when anticipating social threat. To test this prediction, 36 individuals were asked to anticipate and perform a public speaking task. During anticipation, negative self-focused cognitions or relaxation were experimentally induced while self-reported anxiety, autonomic arousal (heart rate, heart rate variability, skin conductance level), and acoustic eye-blink startle response were assessed. As predicted, negative self-focused cognitions mediated the effects of trait social anxiety on self-reported anxiety and heart rate variability during negative anticipation. Furthermore, trait social anxiety predicted increased startle amplitudes. These findings support a central assumption of the cognitive model of social anxiety. PMID:18321469

Inverse Doppler Effects in Broadband Acoustic Metamaterials

PubMed Central

Zhai, S. L.; Zhao, X. P.; Liu, S.; Shen, F. L.; Li, L. L.; Luo, C. R.

2016-01-01

The Doppler effect refers to the change in frequency of a wave source as a consequence of the relative motion between the source and an observer. Veselago theoretically predicted that materials with negative refractions can induce inverse Doppler effects. With the development of metamaterials, inverse Doppler effects have been extensively investigated. However, the ideal material parameters prescribed by these metamaterial design approaches are complex and also challenging to obtain experimentally. Here, we demonstrated a method of designing and experimentally characterising arbitrary broadband acoustic metamaterials. These omni-directional, double-negative, acoustic metamaterials are constructed with ‘flute-like’ acoustic meta-cluster sets with seven double meta-molecules; these metamaterials also overcome the limitations of broadband negative bulk modulus and mass density to provide a region of negative refraction and inverse Doppler effects. It was also shown that inverse Doppler effects can be detected in a flute, which has been popular for thousands of years in Asia and Europe. PMID:27578317

Inverse Doppler Effects in Broadband Acoustic Metamaterials

NASA Astrophysics Data System (ADS)

Zhai, S. L.; Zhao, X. P.; Liu, S.; Shen, F. L.; Li, L. L.; Luo, C. R.

2016-08-01

The Doppler effect refers to the change in frequency of a wave source as a consequence of the relative motion between the source and an observer. Veselago theoretically predicted that materials with negative refractions can induce inverse Doppler effects. With the development of metamaterials, inverse Doppler effects have been extensively investigated. However, the ideal material parameters prescribed by these metamaterial design approaches are complex and also challenging to obtain experimentally. Here, we demonstrated a method of designing and experimentally characterising arbitrary broadband acoustic metamaterials. These omni-directional, double-negative, acoustic metamaterials are constructed with ‘flute-like’ acoustic meta-cluster sets with seven double meta-molecules; these metamaterials also overcome the limitations of broadband negative bulk modulus and mass density to provide a region of negative refraction and inverse Doppler effects. It was also shown that inverse Doppler effects can be detected in a flute, which has been popular for thousands of years in Asia and Europe.

Association of Lyn kinase with membrane rafts determines its negative influence on LPS-induced signaling

PubMed Central

Borzęcka-Solarz, Kinga; Dembińska, Justyna; Hromada-Judycka, Aneta; Traczyk, Gabriela; Ciesielska, Anna; Ziemlińska, Ewelina; Świątkowska, Anna; Kwiatkowska, Katarzyna

2017-01-01

Lipopolysaccharide (LPS) is the component of Gram-negative bacteria that activates Toll-like receptor 4 (TLR4) to trigger proinflammatory responses. We examined the involvement of Lyn tyrosine kinase in TLR4 signaling of macrophages, distinguishing its catalytic activity and intermolecular interactions. For this, a series of Lyn-GFP constructs bearing point mutations in particular domains of Lyn were overexpressed in RAW264 macrophage-like cells or murine peritoneal macrophages, and their influence on LPS-induced responses was analyzed. Overproduction of wild-type or constitutively active Lyn inhibited production of TNF-α and CCL5/RANTES cytokines and down-regulated the activity of NFκB and IRF3 transcription factors in RAW264 cells. The negative influence of Lyn was nullified by point mutations of Lyn catalytic domain or Src homology 2 (SH2) or SH3 domains or of the cysteine residue that undergoes LPS-induced palmitoylation. Depending on the cell type, overproduction of those mutant forms of Lyn could even up-regulate LPS-induced responses, and this effect was reproduced by silencing of endogenous Lyn expression. Simultaneously, the Lyn mutations blocked its LPS-induced accumulation in the raft fraction of RAW264 cells. These data indicate that palmitoylation, SH2- and SH3-mediated intermolecular interactions, and the catalytic activity of Lyn are required for its accumulation in rafts, thereby determining the negative regulation of TLR4 signaling. PMID:28228554

Ultra-thin passivating film induced by vinylene carbonate on highly oriented pyrolytic graphite negative electrode in lithium-ion cell

NASA Astrophysics Data System (ADS)

Matsuoka, O.; Hiwara, A.; Omi, T.; Toriida, M.; Hayashi, T.; Tanaka, C.; Saito, Y.; Ishida, T.; Tan, H.; Ono, S. S.; Yamamoto, S.

We investigated the influence of vinylene carbonate, as an additive molecule, on the decomposition phenomena of electrolyte solution [ethylene carbonate (EC)—ethyl methyl carbonate (EMC) (1:2 by volume) containing 1 M LiPF 6] on a highly oriented pyrolytic graphite (HOPG) negative electrode by using cyclic voltammetry (CV) and atomic force microscopy (AFM). Vinylene carbonate deactivated reactive sites (e.g. radicals and oxides at the defects and the edge of carbon layer) on the cleaved surface of the HOPG negative electrode, and prevented further decomposition of the other solvents there. Further, vinylene carbonate induced an ultra-thin film (less than 1.0 nm in thickness) on the terrace of the basal plane of the HOPG negative electrode, and this film suppressed the decomposition of electrolyte solution on the terraces of the basal plane. We consider that this ultra-thin passivating film is composed of a reduction product of vinylene carbonate (VC), and might have a polymer structure. These induced effects might explain how VC improves the life performance of lithium-ion cells.

Evaluating Expectations about Negative Emotional States of Aggressive Boys Using Bayesian Model Selection

ERIC Educational Resources Information Center

van de Schoot, Rens; Hoijtink, Herbert; Mulder, Joris; Van Aken, Marcel A. G.; Orobio de Castro, Bram; Meeus, Wim; Romeijn, Jan-Willem

2011-01-01

Researchers often have expectations about the research outcomes in regard to inequality constraints between, e.g., group means. Consider the example of researchers who investigated the effects of inducing a negative emotional state in aggressive boys. It was expected that highly aggressive boys would, on average, score higher on aggressive…

Stereotype Threat Reinterpreted as a Regulatory Mismatch

PubMed Central

Grimm, Lisa R.; Markman, Arthur B.; Maddox, W. Todd; Baldwin, Grant C.

2008-01-01

Research documents performance decrements resulting from the activation of a negative task-relevant stereotype. We combine a number of strands of work to identify causes of stereotype threat in a way that allows us to reverse the effects and improve the performance of individuals with negative task-relevant stereotypes. We draw on prior work suggesting that negative stereotypes induce a prevention focus, and other research suggesting that people exhibit greater flexibility when their regulatory focus matches the reward structure of the task. This work suggests that stereotype threat effects emerge from a prevention focus combined with tasks that have an explicit or implicit gains reward structure. We find flexible performance can be induced in individuals who have a negative task-relevant stereotype by using a losses reward structure. We demonstrate the interaction of stereotypes and the reward structure of the task using chronic stereotypes and GRE math problems (Experiment 1), and primed stereotypes and a category learning task (Experiments 2a and 2b). We discuss implications of this research for other work on stereotype threat. PMID:19159133

Emotion word processing: does mood make a difference?

PubMed Central

Sereno, Sara C.; Scott, Graham G.; Yao, Bo; Thaden, Elske J.; O'Donnell, Patrick J.

2015-01-01

Visual emotion word processing has been in the focus of recent psycholinguistic research. In general, emotion words provoke differential responses in comparison to neutral words. However, words are typically processed within a context rather than in isolation. For instance, how does one's inner emotional state influence the comprehension of emotion words? To address this question, the current study examined lexical decision responses to emotionally positive, negative, and neutral words as a function of induced mood as well as their word frequency. Mood was manipulated by exposing participants to different types of music. Participants were randomly assigned to one of three conditions—no music, positive music, and negative music. Participants' moods were assessed during the experiment to confirm the mood induction manipulation. Reaction time results confirmed prior demonstrations of an interaction between a word's emotionality and its frequency. Results also showed a significant interaction between participant mood and word emotionality. However, the pattern of results was not consistent with mood-congruency effects. Although positive and negative mood facilitated responses overall in comparison to the control group, neither positive nor negative mood appeared to additionally facilitate responses to mood-congruent words. Instead, the pattern of findings seemed to be the consequence of attentional effects arising from induced mood. Positive mood broadens attention to a global level, eliminating the category distinction of positive-negative valence but leaving the high-low arousal dimension intact. In contrast, negative mood narrows attention to a local level, enhancing within-category distinctions, in particular, for negative words, resulting in less effective facilitation. PMID:26379570

The influence of positive and negative emotional associations on semantic processing in depression: an fMRI study.

PubMed

Sass, Katharina; Habel, Ute; Kellermann, Thilo; Mathiak, Klaus; Gauggel, Siegfried; Kircher, Tilo

2014-02-01

In depression, patients suffer from emotional and cognitive deficits, among others in semantic processing. If these semantic deficits are cognitive or interact with emotional dysfunctions, is still an open question. The aim of the current study was to investigate the influence of emotional valence on the neural correlates of semantic priming in major depression. In a lexical decision task, positive, negative, and neutral word pairs were presented during fMRI measurement. Nineteen inpatients and 19 demographically matched controls were recruited. Behaviorally, positive and neutral valence induced a priming effect whereas negative valence induced no effect (controls) or even inhibition (slower RT for related stimuli) in patients. At the neural level, the semantic relation effect revealed similar neural activation in right middle frontal regions for patients and controls. Group differences emerged in the right fusiform gyrus and the ACC. Activity associated with positive valence differed at the DLPFC and amygdala and for negative valence at putamen and cerebellum. The activation of amygdala and DLPFC correlated negatively with the severity of depression. To conclude, semantic processing deficits in depression are modulated by emotional valence of the stimulus on the behavioral as well as on neural level in right-lateralized prefrontal areas and the amygdala. The results highlighted an influence of depression severity on emotion information processing as the severity of symptoms correlated negatively with neural responses to positively and negatively valenced information. Hence, the dysfunctional emotion processing may further enhance the cognitive deficits in depression. Copyright © 2012 Wiley Periodicals, Inc.

Oxygen-induced frequency shifts in hyperoxia: a significant component of BOLD signal.

PubMed

Song, Youngkyu; Cho, Gyunggoo; Chun, Song-I; Baek, Jin Hee; Cho, HyungJoon; Kim, Young Ro; Park, Sung Bin; Kim, Jeong Kon

2014-07-01

In comparison to the well-documented significance of intravascular deoxyhemoglobin (deoxyHgb), the effects of dissolved oxygen on the blood-oxygen-level-dependent (BOLD) signal have not been widely reported. Based on the fact that the prolonged inspiration of high oxygen fraction gas can result in up to a sixfold increase of the baseline tissue oxygenation, the current study focused on the influence of dissolved oxygen on the BOLD signal during hyperoxia. As results, our in vitro study revealed that the r1 and r2 (relaxivities) of the oxygen-treated serum were 0.22 mM(-1) · s(-1) and 0.19 mM(-1) · s(-1) , respectively. In an in vivo experiment, hyperoxic respiration induced negative BOLD contrast (i.e. signal decrease) in 18-42% of measured brain regions, voxels with accompanying significant decreases in both the T(*)2 (-12.1% to -19.4%) and T1 (-5.8% to -3.3%) relaxation times. In contrast, the T(*)2 relaxation time significantly increased (11.2% to 14.0%) for the voxels displaying positive BOLD contrast (in 41-50% of the measured brain), which reflected a hyperoxygenation-induced reduction in tissue deoxyHgb concentration. These data imply that hyperoxia-driven BOLD signal changes are primarily determined by the counteracting effects of extravascular oxygen and intravascular deoxyHgb. Oxygen-induced magnetic susceptibility was further demonstrated by the study of 1 min hypoxia, which induced BOLD signal changes opposite to those under hyperoxia. Vasoconstriction was more common in voxels with negative BOLD contrast than in voxels with positive contrast (% change of blood volume, -9.8% to -12.8% versus 2.0% to 2.2%), which further suggests that negative BOLD contrast is mainly evoked by an increase in extravascular oxygen concentration. Conclusively, frequency shifts, which are induced by the accumulation of oxygen molecules and associated magnetic field inhomogeneity, are a significant source of the negative BOLD contrast during hyperoxia. Copyright © 2014 John Wiley & Sons, Ltd.

Plastic and evolutionary responses to heat stress in a temperate dung fly: negative correlation between basal and induced heat tolerance?

PubMed

Esperk, T; Kjaersgaard, A; Walters, R J; Berger, D; Blanckenhorn, W U

2016-05-01

Extreme weather events such as heat waves are becoming more frequent and intense. Populations can cope with elevated heat stress by evolving higher basal heat tolerance (evolutionary response) and/or stronger induced heat tolerance (plastic response). However, there is ongoing debate about whether basal and induced heat tolerance are negatively correlated and whether adaptive potential in heat tolerance is sufficient under ongoing climate warming. To evaluate the evolutionary potential of basal and induced heat tolerance, we performed experimental evolution on a temperate source population of the dung fly Sepsis punctum. Offspring of flies adapted to three thermal selection regimes (Hot, Cold and Reference) were subjected to acute heat stress after having been exposed to either a hot-acclimation or non-acclimation pretreatment. As different traits may respond differently to temperature stress, several physiological and life history traits were assessed. Condition dependence of the response was evaluated by exposing juveniles to different levels of developmental (food restriction/rearing density) stress. Heat knockdown times were highest, whereas acclimation effects were lowest in the Hot selection regime, indicating a negative association between basal and induced heat tolerance. However, survival, adult longevity, fecundity and fertility did not show such a pattern. Acclimation had positive effects in heat-shocked flies, but in the absence of heat stress hot-acclimated flies had reduced life spans relative to non-acclimated ones, thereby revealing a potential cost of acclimation. Moreover, body size positively affected heat tolerance and unstressed individuals were less prone to heat stress than stressed flies, offering support for energetic costs associated with heat tolerance. Overall, our results indicate that heat tolerance of temperate insects can evolve under rising temperatures, but this response could be limited by a negative relationship between basal and induced thermotolerance, and may involve some but not other fitness-related traits. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

ONC201 demonstrates anti-tumor effects in both triple negative and non-triple negative breast cancers through TRAIL-dependent and TRAIL-independent mechanisms

PubMed Central

Ralff, Marie D.; Kline, Christina L.B.; Küçükkase, Ozan C; Wagner, Jessica; Lim, Bora; Dicker, David T.; Prabhu, Varun V.; Oster, Wolfgang; El-Deiry, Wafik S.

2017-01-01

Breast cancer is a major cause of cancer-related death. TRAIL has been of interest as a cancer therapeutic, but only a subset of triple negative breast cancers (TNBC) is sensitive to TRAIL. The small molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has entered clinical trials in advanced cancers. Here we show that ONC201 is efficacious against both TNBC and non-TNBC cells (n=13). A subset of TNBC and non-TNBC cells succumb to ONC201-induced cell death. In 2/8 TNBC cell lines, ONC201 treatment induces caspase-8 cleavage and cell death that is blocked by TRAIL-neutralizing antibody RIK2. The pro-apoptotic effect of ONC201 translates to in vivo efficacy in the MDA-MB-468 xenograft model. In most TNBC lines tested (6/8) ONC201 has an anti-proliferative effect but does not induce apoptosis. ONC201 decreases cyclin D1 expression and causes an accumulation of cells in the G1 phase of the cell cycle. pRb expression is associated with sensitivity to the anti-proliferative effects of ONC201, and the compound synergizes with taxanes in less sensitive cells. All non-TNBC cells (n=5) are growth inhibited following ONC201 treatment, and unlike what has been observed with TRAIL, a subset (n=2) show PARP cleavage. In these cells, cell death induced by ONC201 is TRAIL-independent. Our data demonstrate that ONC201 has potent anti-proliferative and pro-apoptotic effects in a broad range of breast cancer subtypes, through TRAIL-dependent and TRAIL-independent mechanisms. These findings develop a pre-clinical rationale for developing ONC201 as a single agent and/or in combination with approved therapies in breast cancer. PMID:28424227

Effects of retinoic acids on the dendritic morphology of cultured hippocampal neurons.

PubMed

Liu, Ying; Kagechika, Hiroyuki; Ishikawa, Junko; Hirano, Hitoshi; Matsukuma, Satoshi; Tanaka, Kazuko; Nakamura, Shoji

2008-08-01

Vitamin A-derived retinoic acids (RAs) are known to exert a variety of biological actions, including modulatory effects on cell differentiation and apoptosis. A recent study has demonstrated that 13-cis-RA and all-trans-RA suppressed neurogenesis in the dentate gyrus of the hippocampus in adult mice. The present experiments were performed to see whether 13-cis-RA and all-trans-RA could alter the dendritic morphology of cultured hippocampal neurons via RA receptors: retinoic acid receptor (RAR) and retinoid X receptor (RXR). High doses of 13-cis-RA and all-trans-RA exerted a negative effect on the cultured hippocampal neurons, while a low dose of 13-cis-RA but not all-trans-RA caused a positive effect. The negative changes induced by 13-cis-RA and all-trans-RA were antagonized by RXR antagonists and RAR antagonists, respectively. The positive changes induced by a low dose of 13-cis-RA were blocked by both RXR antagonists and RAR antagonists. These results suggest that RAs at high concentrations cause a negative effect on the dendritic morphology of cultured hippocampal neurons through RA receptors, while RAs at low concentrations exert a positive influence on cultured hippocampal neurons.

INTERNALIZATION AND DEGRADATION OF THE GLUTAMATE TRANSPORTER GLT-1 IN RESPONSE TO PHORBOL ESTER

PubMed Central

Susarla, Bala T.S.; Robinson, Michael B.

2008-01-01

Activation of protein kinase C (PKC) decreases the activity and cell surface expression of the predominant forebrain glutamate transporter, GLT-1. In the present study, C6 glioma were used as a model system to define the mechanisms that contribute to this decrease in cell surface expression and to determine the fate of internalized transporter. As was previously observed, phorbol 12-myristate 13-acetate (PMA) caused a decrease in biotinylated GLT-1. This effect was blocked by sucrose or by co-expression with a dominant-negative variant of dynamin 1, and it was attenuated by co-expression with a dominant-negative variant of the clathrin heavy chain. Depletion of cholesterol with methyl-β-cyclodextrin, co-expression with a dominant-negative caveolin-1 mutant (Cav1/S80E), co-expression with dominant-negative variants of Eps15 (epidermal-growth-factor receptor pathway substrate clone 15), or co-expression with dominant-negative Arf6 (T27N) had no effect on the PMA-induced loss of biotinylated GLT-1. Long-term treatment with PMA caused a time-dependent loss of biotinylated GLT-1 and decreased the levels of GLT-1 protein. Inhibitors of lysosomal degradation (chloroquine or ammonium chloride) or co-expression with a dominant-negative variant of a small GTPase implicated in trafficking to lysosomes (Rab7) prevented the PMA-induced decrease in protein and caused an intracellular accumulation of GLT-1. These results suggest that the PKC-induced redistribution of GLT-1 is dependent upon clathrin-mediated endocytosis. These studies identify a novel mechanism by which the levels of GLT-1 could be rapidly down-regulated via lysosomal degradation. The possibility that this mechanism may contribute to the loss of GLT-1 observed after acute insults to the CNS is discussed. PMID:17919781

Dissociable neural systems underwrite logical reasoning in the context of induced emotions with positive and negative valence.

PubMed

Smith, Kathleen W; Vartanian, Oshin; Goel, Vinod

2014-01-01

How emotions influence syllogistic reasoning is not well understood. fMRI was employed to investigate the effects of induced positive or negative emotion on syllogistic reasoning. Specifically, on a trial-by-trial basis participants were exposed to a positive, negative, or neutral picture, immediately prior to engagement in a reasoning task. After viewing and rating the valence and intensity of each picture, participants indicated by keypress whether or not the conclusion of the syllogism followed logically from the premises. The content of all syllogisms was neutral, and the influence of belief-bias was controlled for in the study design. Emotion did not affect reasoning performance, although there was a trend in the expected direction based on accuracy rates for the positive (63%) and negative (64%) versus neutral (70%) condition. Nevertheless, exposure to positive and negative pictures led to dissociable patterns of neural activation during reasoning. Therefore, the neural basis of deductive reasoning differs as a function of the valence of the context.

Dissociable Neural Systems Underwrite Logical Reasoning in the Context of Induced Emotions with Positive and Negative Valence

PubMed Central

Smith, Kathleen W.; Vartanian, Oshin; Goel, Vinod

2014-01-01

How emotions influence syllogistic reasoning is not well understood. fMRI was employed to investigate the effects of induced positive or negative emotion on syllogistic reasoning. Specifically, on a trial-by-trial basis participants were exposed to a positive, negative, or neutral picture, immediately prior to engagement in a reasoning task. After viewing and rating the valence and intensity of each picture, participants indicated by keypress whether or not the conclusion of the syllogism followed logically from the premises. The content of all syllogisms was neutral, and the influence of belief-bias was controlled for in the study design. Emotion did not affect reasoning performance, although there was a trend in the expected direction based on accuracy rates for the positive (63%) and negative (64%) versus neutral (70%) condition. Nevertheless, exposure to positive and negative pictures led to dissociable patterns of neural activation during reasoning. Therefore, the neural basis of deductive reasoning differs as a function of the valence of the context. PMID:25294997

Implantation reduces the negative effects of bio-logging devices on birds.

PubMed

White, Craig R; Cassey, Phillip; Schimpf, Natalie G; Halsey, Lewis G; Green, Jonathan A; Portugal, Steven J

2013-02-15

Animal-borne logging or telemetry devices are widely used for measurements of physiological and movement data from free-living animals. For such measurements to be relevant, however, it is essential that the devices themselves do not affect the data of interest. A recent meta-analysis reported an overall negative effect of these devices on the birds that bear them, i.e. on nesting productivity, clutch size, nest initiation date, offspring quality, body condition, flying ability, foraging behaviours, energy expenditure and survival rate. Method of attachment (harness, collar, glue, anchor, implant, breast-mounted or tailmount) had no influence on the strength of these effects but anchored and implanted transmitters had the highest reported rates of device-induced mortality. Furthermore, external devices, but not internal devices, caused an increase in 'device-induced behaviour' (comfort behaviours such as preening, fluffing and stretching, and unrest activities including unquantifiable 'active' behaviours). These findings suggest that, with the exception of device-induced behaviour, external attachment is preferable to implantation. In the present study we undertake a meta-analysis of 183 estimates of device impact from 39 studies of 36 species of bird designed to explicitly compare the effects of externally attached and surgically implanted devices on a range of traits, including condition, energy expenditure and reproduction. In contrast to a previous study, we demonstrate that externally attached devices have a consistent detrimental effect (i.e. negative influences on body condition, reproduction, metabolism and survival), whereas implanted devices have no consistent effect. We also show that the magnitude of the negative effect of externally attached devices decreases with time. We therefore conclude that device implantation is preferable to external attachment, providing that the risk of mortality associated with the anaesthesia and surgery required for implantation can be mitigated. We recommend that studies employing external devices use devices that can be borne for long periods, and, wherever possible, deploy devices in advance of the time period of interest.

The negative effect of hypokinesia involving injury and preventive measures

NASA Technical Reports Server (NTRS)

Izakson, K. A.

1981-01-01

The optimum length of bed rest for athletes suffering from broken bones is considered. Negative effects of hypokinesia induced by bed rest include general weakness and deconditioning of the muscles as well as sleeplessness, headaches, muscle pain, constipation, unstable pulse and arterial pressure, and changes in reflexes. This is considered to be the result of a vegetative dysfunction induced by the decreased flow of nerve impulses and a decrease in interoceptive and exteroceptive signals. The briefest possible period of bed rest, followed by an increase in motor activity, the prescription of a large quantity of LFK, and an active program of physical therapy are recommended. The symptomology associated with hypokinesia disappears after one month of free motor activity.

Good things don't come easy (to mind): explaining framing effects in judgments of truth.

PubMed

Hilbig, Benjamin E

2012-01-01

Recently, the general phenomenon of a positive-negative-asymmetry was extended to judgments of truth. That is, negatively framed statements were shown to receive substantially higher truth ratings than formally equivalent statements framed positively. However, the cognitive mechanisms underlying this effect are unknown, so far. In the current work, two potential accounts are introduced and tested against each other in three experiments: On the one hand, negative framing may induce increased elaboration and thereby persuasion. Alternatively, negative framing could yield faster retrieval or generation of evidence and thus influence subjective veracity via experiential fluency. Two experiments drawing on response latencies and one manipulating the delay between information acquisition and judgment provide support for the fluency-based account. Overall, results replicate and extend the negatively-biased framing effect in truth judgments and show that processing fluency may account for it. © 2011 Hogrefe Publishing

Triorganotin Derivatives Induce Cell Death Effects on L1210 Leukemia Cells at Submicromolar Concentrations Independently of P-glycoprotein Expression.

PubMed

Bohacova, Viera; Seres, Mario; Pavlikova, Lucia; Kontar, Szilvia; Cagala, Martin; Bobal, Pavel; Otevrel, Jan; Brtko, Julius; Sulova, Zdena; Breier, Albert

2018-05-01

The acceleration of drug efflux activity realized by plasma membrane transporters in neoplastic cells, particularly by P-glycoprotein (P-gp, ABCB1 member of the ABC transporter family), represents a frequently observed molecular cause of multidrug resistance (MDR). This multiple resistance represents a real obstacle in the effective chemotherapy of neoplastic diseases. Therefore, identifying cytotoxic substances that are also effective in P-gp overexpressing cells may be useful for the rational design of substances for the treatment of malignancies with developed MDR. Here, we showed that triorganotin derivatives—tributyltin-chloride (TBT-Cl), tributyltin-bromide (TBT-Br), tributyltin-iodide (TBT-I) and tributyltin-isothiocyanate (TBT-NCS) or triphenyltin-chloride (TPT-Cl) and triphenyltin-isothiocyanate (TPT-NCS)—could induce the death of L1210 mice leukemia cells at a submicromolar concentration independently of P-gp overexpression. The median lethal concentration obtained for triorganotin derivatives did not exceed 0.5 µM in the induction of cell death of either P-gp negative or P-gp positive L1210 cells. Apoptosis related to regulatory pathway of Bcl-2 family proteins seems to be the predominant mode of cell death in either P-gp negative or P-gp positive L1210 cells. TBT-Cl and TBT-Br were more efficient with L1210 cells overexpressing P-gp than with their counterpart P-gp negative cells. In contrast, TBT-I and TPT-NCS induced a more pronounced cell death effect on P-gp negative cells than on P-gp positive cells. Triorganotin derivatives did not affect P-gp efflux in native cells measured by calcein retention within the cells. Taken together, we assumed that triorganotin derivatives represent substances suitable for suppressing the viability of P-gp positive malignant cells.

A novel concurrent pictorial choice model of mood-induced relapse in hazardous drinkers.

PubMed

Hardy, Lorna; Hogarth, Lee

2017-12-01

This study tested whether a novel concurrent pictorial choice procedure, inspired by animal self-administration models, is sensitive to the motivational effect of negative mood induction on alcohol-seeking in hazardous drinkers. Forty-eight hazardous drinkers (scoring ≥7 on the Alcohol Use Disorders Inventory) recruited from the community completed measures of alcohol dependence, depression, and drinking coping motives. Baseline alcohol-seeking was measured by percent choice to enlarge alcohol- versus food-related thumbnail images in two alternative forced-choice trials. Negative and positive mood was then induced in succession by means of self-referential affective statements and music, and percent alcohol choice was measured after each induction in the same way as baseline. Baseline alcohol choice correlated with alcohol dependence severity, r = .42, p = .003, drinking coping motives (in two questionnaires, r = .33, p = .02 and r = .46, p = .001), and depression symptoms, r = .31, p = .03. Alcohol choice was increased by negative mood over baseline (p < .001, ηp2 = .280), and matched baseline following positive mood (p = .54, ηp2 = .008). The negative mood-induced increase in alcohol choice was not related to gender, alcohol dependence, drinking to cope, or depression symptoms (ps ≥ .37). The concurrent pictorial choice measure is a sensitive index of the relative value of alcohol, and provides an accessible experimental model to study negative mood-induced relapse mechanisms in hazardous drinkers. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Acute stress negatively affects object recognition early memory consolidation and memory retrieval unrelated to state-dependency.

PubMed

Nelissen, Ellis; Prickaerts, Jos; Blokland, Arjan

2018-06-01

It is well known that stress affects memory performance. However, there still appears to be inconstancy in literature about how acute stress affects the different stages of memory: acquisition, consolidation and retrieval. In this study, we exposed rats to acute stress and measured the effect on memory performance in the object recognition task as a measure for episodic memory. Stress was induced 30 min prior to the learning phase to affect acquisition, directly after the learning phase to affect consolidation, or 30 min before the retrieval phase to affect retrieval. Additionally, we induced stress both 30 min prior to the learning phase and 30 min prior to the retrieval phase to test whether the effects were related to state-dependency. As expected, we found that acute stress did not affect acquisition but had a negative impact on retrieval. To our knowledge, we are the first to show that early consolidation was negatively affected by acute stress. We also show that stress does not have a state-dependent effect on memory. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of extracts and isolated compounds from safflower on some index of promoting blood circulation and regulating menstruation.

PubMed

Yao, Dong; Wang, Zheng; Miao, Li; Wang, Linyan

2016-09-15

Carthamus tinctorius is used as one of the Traditional Chinese Medicine (TCM) materials in prescriptions and composite to promote blood circulation to remove blood stasis, regulate menstruation and alleviate pain for over 2500 years. Modern pharmacological experiments have demonstrated that safflower has wide-reaching biological activities, including dilating coronary artery, modulating immune system, improving myocardial ischemia, anticoagulation and thromboprophylaxis, antioxidation, antihypoxic, antiaging, antifatigue, antiinflammation, anti-hepatic fibrosis, antitumor, analgesia, etc. Platelet aggregation of safflower extract and main constituents in safflower were determined by PAF-induced or ADP-induced platelet aggregation in vitro. Anticoagulation activity was measured by clotting assay of thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT) according to the methods provided by the biological reagents provider (Sun Biochemical). Antioxidant effects of safflower were assessed using DPPH radical-scavenging activity test, ABTS radical-scavenging activity test and ferric reducing antioxidant power test. In addition, rats ovary granulosa cell proliferation activity was used for the bio-activity index on regulate menstruation of safflower. Safflower extract at the concentration of 0.7g/mL (P<0.001) and 0.5g/mL (P<0.01) had significantly antagonistic effect on PAF-induced platelet aggregation, compared with negative control. And the anti-platelet aggregation of 0.7g/mL safflower extract was significantly stronger than that of positive control (P<0.001). 0.7g/mL of hydroxysafflor yellow A (P<0.01), anhydrosafflor yellow B (P<0.05), 6-hydroxykaempferol-3-O-rutinoside (P<0.05), keampferol-3-O-β-rutinoside (P<0.01) had significant effect on platelet aggregation compared with negative control. Safflower extract at the concentration of 0.5g/mL (P<0.001) and 0.125g/mL (P<0.01) could significantly inhibit ADP-induced platelet aggregation, compared with negative control. And antagonistic effect of safflower extract was significantly stronger than the effect of positive control (P<0.001). Adenosine (P<0.001), anhydrosafflor yellow B (P<0.01) and 6-hydroxykaempferol-3-O-rutinoside (P<0.01) at the concentration of 0.5g/mL had significant effect on ADP-induced platelet aggregation compared with negative control. 0.125g/mL of adenosine (P<0.05) had significant effect on ADP-induced platelet aggregation compared with negative control. The effect of 0.5g/mL adenosine (P<0.01) and 6-hydroxykaempferol-3-O-rutinoside (P<0.05) was significantly stronger than that of positive control. Safflower extract at the concentration of 0.7mg/mL (P<0.001) and 0.5mg/mL (P<0.001) had significantly anticoagulation activity in PT, TT and APTT, compared with negative control. However, the respective compound didn't have significant effect on PT and TT at experiment concentration. At the concentration of 0.7mg/mL, hydroxysafflor yellow A (P<0.01), 6-hydroxykaempferol-3,6,7-tri-O-β-d-glucoside (P<0.05), 6-hydroxyapigenin-6-O-glucoside-7-O-glucuronide (P<0.01), anhydrosafflor yellow B (P<0.001), 6-hydroxykaempferol-3-O-rutinoside (P<0.05) and keampferol-3-O-β-rutinoside (P<0.05) significantly prolonged APTT, compared with negative control. At the concentration of 0.5mg/mL, hydroxysafflor yellow A (P<0.05), 6-hydroxyapigenin-6-O-glucoside-7-O-glucuronide (P<0.05), anhydrosafflor yellow B (P<0.001), 6-hydroxykaempferol-3-O-rutinoside (P<0.05) and keampferol-3-O-β-rutinoside (P<0.05) could significantly prolong APTT, compared with negative control. From the results of DPPH, ABTS radical scavenging activity test and Fe(3+) reduction power test, 5mg/mL, 2.5mg/mL and 1.25mg/mL safflower extract had antioxidant effects. Every compound with each concentration (5mg/mL, 2.5mg/mL and 1.25mg/mL) had significant effect on Fe(3+) reduction power (P<0.001 vs. negative control). Safflower extract, cytidine, 6-hydroxy-kaempferol-3,6-di-O-β-d-glucoside-7-O-β-d-glucuronide, 6-hydroxykaemp-ferol-3,6,7-tri-O-β-D-glucoside and keampferol-3-O-β-rutinoside significantly promoted ovarian granulosa cell proliferation. Based on previous researches, the activities of safflower extract and pure compounds isolated from safflower were studied in this paper. This study found some compounds with the effects of anti-platelet aggregation, anticoagulation, antioxidation and ovarian granulosa cell proliferation, and further revealed the possible pharmacological mechanism of safflower. Copyright © 2016. Published by Elsevier Ireland Ltd.

Development of Preparatory Activity Indexed by the Contingent Negative Variation in Children

ERIC Educational Resources Information Center

Flores, Angelica B.; Digiacomo, Marcia R.; Meneres, Susana; Trigo, Eva; Gomez, Carlos M.

2009-01-01

Objectives: The present study investigated the effect of age on task-specific preparatory activation induced by a spatial cue using the central cue Posner's paradigm. The behavioral responses and the contingent negative variation (CNV) generated between S1 (the warning stimulus) and S2 (the imperative stimulus) were compared between 16 healthy…

Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice

PubMed Central

Reber, Stefan O.; Siebler, Philip H.; Donner, Nina C.; Morton, James T.; Smith, David G.; Kopelman, Jared M.; Lowe, Kenneth R.; Wheeler, Kristen J.; Fox, James H.; Hassell, James E.; Greenwood, Benjamin N.; Jansch, Charline; Lechner, Anja; Schmidt, Dominic; Uschold-Schmidt, Nicole; Füchsl, Andrea M.; Langgartner, Dominik; Walker, Frederick R.; Hale, Matthew W.; Lopez Perez, Gerardo; Van Treuren, Will; González, Antonio; Halweg-Edwards, Andrea L.; Fleshner, Monika; Raison, Charles L.; Rook, Graham A.; Peddada, Shyamal D.; Knight, Rob

2016-01-01

The prevalence of inflammatory diseases is increasing in modern urban societies. Inflammation increases risk of stress-related pathology; consequently, immunoregulatory or antiinflammatory approaches may protect against negative stress-related outcomes. We show that stress disrupts the homeostatic relationship between the microbiota and the host, resulting in exaggerated inflammation. Repeated immunization with a heat-killed preparation of Mycobacterium vaccae, an immunoregulatory environmental microorganism, reduced subordinate, flight, and avoiding behavioral responses to a dominant aggressor in a murine model of chronic psychosocial stress when tested 1–2 wk following the final immunization. Furthermore, immunization with M. vaccae prevented stress-induced spontaneous colitis and, in stressed mice, induced anxiolytic or fear-reducing effects as measured on the elevated plus-maze, despite stress-induced gut microbiota changes characteristic of gut infection and colitis. Immunization with M. vaccae also prevented stress-induced aggravation of colitis in a model of inflammatory bowel disease. Depletion of regulatory T cells negated protective effects of immunization with M. vaccae on stress-induced colitis and anxiety-like or fear behaviors. These data provide a framework for developing microbiome- and immunoregulation-based strategies for prevention of stress-related pathologies. PMID:27185913

TG-interacting factor transcriptionally induced by AKT/FOXO3A is a negative regulator that antagonizes arsenic trioxide-induced cancer cell apoptosis

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

Liu, Zi-Miao; Tseng, Hong-Yu; Cheng, Ya-Ling

2015-05-15

Arsenic trioxide (ATO) is a multi-target drug approved by the Food and Drug Administration as the first-line chemotherapeutic agent for the treatment of acute promyelocytic leukemia. In addition, several clinical trials are being conducted with arsenic-based drugs for the treatment of other hematological malignancies and solid tumors. However, ATO's modest clinical efficacy on some cancers, and potential toxic effects on humans have been reported. Determining how best to reduce these adverse effects while increasing its therapeutic efficacy is obviously a critical issue. Previously, we demonstrated that the JNK-induced complex formation of phosphorylated c-Jun and TG-interacting factor (TGIF) antagonizes ERK-induced cyclin-dependentmore » kinase inhibitor CDKN1A (p21{sup WAF1/CIP1}) expression and resultant apoptosis in response to ATO in A431 cells. Surprisingly, at low-concentrations (0.1–0.2 μM), ATO increased cellular proliferation, migration and invasion, involving TGIF expression, however, at high-concentrations (5–20 μM), ATO induced cell apoptosis. Using a promoter analysis, TGIF was transcriptionally regulated by ATO at the FOXO3A binding site (− 1486 to − 1479 bp) via the c-Src/EGFR/AKT pathway. Stable overexpression of TGIF promoted advancing the cell cycle into the S phase, and attenuated 20 μM ATO-induced apoptosis. Furthermore, blockage of the AKT pathway enhanced ATO-induced CDKN1A expression and resultant apoptosis in cancer cells, but overexpression of AKT1 inhibited CDKN1A expression. Therefore, we suggest that TGIF is transcriptionally regulated by the c-Src/EGFR/AKT pathway, which plays a role as a negative regulator in antagonizing ATO-induced CDKN1A expression and resultant apoptosis. Suppression of these antagonistic effects might be a promising therapeutic strategy toward improving clinical efficacy of ATO. - Highlights: • ATO-induced biphasic survival responses of cancer cells depend on low- or high-concentrations. • TGIF mediates low-concentration ATO-induced cancer cell proliferation, migration, and invasion. • ATO transcriptionally regulates TGIF expression via c-Src/EGFR/AKT/FOXO3A signalings. • Increased TGIF or AKT activation attenuates high-concentration ATO-induced CDKN1A expression and cellular apoptosis. • Suppression of these negative regulators might be a promising therapeutic strategy to improve therapeutic efficacy of ATO.« less

Effect of sample preparation on the discrimination of bacterial isolates cultured in liquid nutrient media using laser induced breakdown spectroscopy

USDA-ARS?s Scientific Manuscript database

Laser induced breakdown spectroscopy (LIBS) is used as the basis for discrimination between 2 genera of gram-negative bacteria and 2 genera of gram-positive bacteria representing pathogenic threats commonly found in poultry processing rinse waters. Because LIBS-based discrimination relies primarily ...

Meditation-induced neuroplastic changes in amygdala activity during negative affective processing.

PubMed

Leung, Mei-Kei; Lau, Way K W; Chan, Chetwyn C H; Wong, Samuel S Y; Fung, Annis L C; Lee, Tatia M C

2018-06-01

Recent evidence suggests that the effects of meditation practice on affective processing and resilience have the potential to induce neuroplastic changes within the amygdala. Notably, literature speculates that meditation training may reduce amygdala activity during negative affective processing. Nonetheless, studies have thus far not verified this speculation. In this longitudinal study, participants (N = 21, 9 men) were trained in awareness-based compassion meditation (ABCM) or matched relaxation training. The effects of meditation training on amygdala activity were examined during passive viewing of affective and neutral stimuli in a non-meditative state. We found that the ABCM group exhibited significantly reduced anxiety and right amygdala activity during negative emotion processing than the relaxation group. Furthermore, ABCM participants who performed more compassion practice had stronger right amygdala activity reduction during negative emotion processing. The lower right amygdala activity after ABCM training may be associated with a general reduction in reactivity and distress. As all participants performed the emotion processing task in a non-meditative state, it appears likely that the changes in right amygdala activity are carried over from the meditation practice into the non-meditative state. These findings suggest that the distress-reducing effects of meditation practice on affective processing may transfer to ordinary states, which have important implications on stress management.

miR-429 mediates δ-tocotrienol-induced apoptosis in triple-negative breast cancer cells by targeting XIAP

PubMed Central

Wang, Chen; Ju, Hong; Shen, Chunyan; Tong, Zhongsheng

2015-01-01

Vitamin E δ-tocotrienol has been reported to possess anticancer activity both in vitro and in vivo. However, the underlying molecular mechanisms of δ-tocotrienol induced apoptosis in triple-negative breast cancer are not fully understood. Here, we reported that microRNA-429 (miR-429) is up-regulated in two TNBC cell lines (MDA-MB-231 and MDA-MB-468), treated with δ-tocotrienol. Inhibition of miR-429 may partially rescue the apoptosis induced by δ-tocotrienol in MDA-MB-231 cells. We also showed that the forced expression of miR-429 was sufficient to lead to apoptosis in MDA-MB-231 cells. Furthermore, we identified X-linked inhibitor of apoptosis protein (XIAP) as one of miR-429’s target genes. These results suggest that the activation of miR-429 by δ-tocotrienol may be an effective approach for the prevention and treatment of triple-negative breast cancer. PMID:26629059

Diadenosine tetraphosphate stimulates atrial ANP release via A(1) receptor: involvement of K(ATP) channel and PKC.

PubMed

Yuan, Kuichang; Cao, Chunhua; Bai, Guang Yi; Kim, Sung Zoo; Kim, Suhn Hee

2007-07-01

Diadenosine polyphosphates (APnAs) are endogenous compounds and exert diverse cardiovascular functions. However, the effects of APnAs on atrial ANP release and contractility have not been studied. In this study, the effects of diadenosine tetraphosphate (AP4A) on atrial ANP release and contractility, and their mechanisms were studied using isolated perfused rat atria. Treatment of atria with AP4A resulted in decreases in atrial contractility and extracellular fluid (ECF) translocation whereas ANP secretion and cAMP levels in perfusate were increased in a dose-dependent manner. These effects of AP4A were attenuated by A(1) receptor antagonist but not by A(2A) or A(3) receptor antagonist. Other purinoceptor antagonists also did not show any effects on AP4A-induced ANF release and contractility. The increment of ANP release and negative inotropy induced by AP4A was similar to those induced by AP3A, AP5A, and AP6A. Protein kinase A inhibitors accentuated AP4A-induced ANP secretion. In contrast, an inhibitor of phospholipase C, protein kinase C or sarcolemma K(ATP) channel completely blocked AP4A-induced ANP secretion. However, an inhibitor of adenylyl cyclase or mitochondria K(ATP) channel had no significant modification of AP4A effects. These results suggest that AP4A regulates atrial inotropy and ANP release mainly through A(1) receptor signaling involving phospholipase C-protein kinase C and sarcolemmal K(ATP) channel and that protein kinase A negatively modulates the effects of AP4A.

The association between attention control, anxiety, and depression: the indirect effects of repetitive negative thinking and mood recovery.

PubMed

Kertz, Sarah J; Stevens, Kimberly T; Klein, Keith P

2017-07-01

Attention control deficits and repetitive negative thinking (RNT; i.e., rumination) may be key factors in the development and persistence of depression and anxiety, although their role in symptom development remains poorly understood. This represents a gap in the literature, as interventions targeting attention control and associated RNT may enhance interventions and prevent costly relapse. The current study was designed to examine the serial indirect effects of transdiagnostic RNT and negative affect recovery following a lab-induced stressor on the association between attention control deficits and trait anxiety and depression. Participants were N = 583 university students who completed validated measures of RNT, anxiety, depression, and mood ratings pre- and post-stressor. Stress was induced using a modified version of the Trier Social Stress Test. Results of cross-sectional indirect effects models indicated that RNT and mood recovery explained the association between attention control deficits and trait anxiety and depression. Results from reversed models indicated that only the indirect effect of RNT was significant. Findings suggest that RNT and mood recovery processes play an important role in explaining anxiety and depression symptoms. Additional work is needed to examine their role in symptom development and maintenance over time.

Remembering episodic memories is not necessary for forgetting of negative words: Semantic retrieval can cause forgetting of negative words.

PubMed

Kobayashi, Masanori; Tanno, Yoshihiko

2015-06-01

Retrieval of a memory can induce forgetting of other related memories, which is known as retrieval-induced forgetting. Although most studies have investigated retrieval-induced forgetting by remembering episodic memories, this also can occur by remembering semantic memories. The present study shows that retrieval of semantic memories can lead to forgetting of negative words. In two experiments, participants learned words and then engaged in retrieval practice where they were asked to recall words related to the learned words from semantic memory. Finally, participants completed a stem-cued recall test for the learned words. The results showed forgetting of neutral and negative words, which was characteristic of semantic retrieval-induced forgetting. A certain degree of overlapping features, except same learning episode, is sufficient to cause retrieval-induced forgetting of negative words. Given the present results, we conclude that retrieval-induced forgetting of negative words does not require recollection of episodic memories.

Selective mood-induced body image disparagement and enhancement effects: are they due to cognitive priming or subjective mood?

PubMed

Rotenberg, Ken J; Taylor, Daniel; Davis, Ron

2004-04-01

The study evaluated the effects of mood induction procedures on body image. Eighty female undergraduates participated in combinations of two valences (negative vs. positive) and two types (self-referent vs. other-referent) of mood induction procedures (MIPs). A measure of subjective mood and seven measures of body image were administered before and after the MIPs. Individuals in the self-referent MIP who had high negative body image at the pretest demonstrated increases in negative body image after exposure to the negative valence MIP (a disparagement effect) and decreases in negative body image after exposure to the positive valence MIP (an enhancement effect). This pattern was not evident in the other-referent MIP. Also, changes in negative body image were not appreciably associated with changes in subjective mood. The findings yielded support for the cognitive priming hypothesis but not for the subjective mood hypothesis. Further means of examining the cognitive priming hypothesis were outlined. Copyright 2004 by Wiley Periodicals, Inc. Int J Eat Disord 35: 317-332, 2004.

Refractive Changes Induced by Spherical Aberration in Laser Correction Procedures: An Adaptive Optics Study.

PubMed

Amigó, Alfredo; Martinez-Sorribes, Paula; Recuerda, Margarita

2017-07-01

To study the effect on vision of induced negative and positive spherical aberration within the range of laser vision correction procedures. In 10 eyes (mean age: 35.8 years) under cyclopegic conditions, spherical aberration values from -0.75 to +0.75 µm in 0.25-µm steps were induced by an adaptive optics system. Astigmatism and spherical refraction were corrected, whereas the other natural aberrations remained untouched. Visual acuity, depth of focus defined as the interval of vision for which the target was still perceived acceptable, contrast sensitivity, and change in spherical refraction associated with the variation in pupil diameter from 6 to 2.5 mm were measured. A refractive change of 1.60 D/µm of induced spherical aberration was obtained. Emmetropic eyes became myopic when positive spherical aberration was induced and hyperopic when negative spherical aberration was induced (R 2 = 81%). There were weak correlations between spherical aberration and visual acuity or depth of focus (R 2 = 2% and 3%, respectively). Contrast sensitivity worsened with the increment of spherical aberration (R 2 = 59%). When pupil size decreased, emmetropic eyes became hyperopic when preexisting spherical aberration was positive and myopic when spherical aberration was negative, with an average refractive change of 0.60 D/µm of spherical aberration (R 2 = 54%). An inverse linear correlation exists between the refractive state of the eye and spherical aberration induced within the range of laser vision correction. Small values of spherical aberration do not worsen visual acuity or depth of focus, but positive spherical aberration may induce night myopia. In addition, the changes in spherical refraction when the pupil constricts may worsen near vision when positive spherical aberration is induced or improve it when spherical aberration is negative. [J Refract Surg. 2017;33(7):470-474.]. Copyright 2017, SLACK Incorporated.

Investigation on financial crises with the negative-information-propagation-induced model

NASA Astrophysics Data System (ADS)

Fan, Feng-Hua; Deng, Yanbin; Huang, Yong-Chang

2017-03-01

We first argue about the similarity between the propagation phenomenon of negative information about potential deterioration of economic situation in group of investors and the propagation phenomenon of infectious disease in crowd Applying the negative-information-propagation-induced model built based on above argument, we investigate the relationship between the generation of financial crises and propagation effects of negative information We introduce the discrimination parameter to distinguish whether or not negative information will be propagated extensively in group of investors. We also introduce the target critical value of financial crises. By comparing the theoretically predicted ratio of the long term projected number of total investors to the total number of investors at some time as initial time with target critical value of financial crises, the model can provide real-time monitoring of whether the curve of total number of investors is progressing toward the direction of generating financial crises or running on track of financial markets safety. If at some time this ratio is computed to be less than the target critical value of financial crises, governments can take relevant measures to prevent the generation of financial crises in advance Governments' interference helps to recover the confidence of investors so that they never will again believe in negative information to continue their investment. Results from theoretical and numerical analysis show that the number of investors who hold the belief of potential deterioration of economic situation, and the number of investors who withdraw capital and depart from financial markets for avoiding business loss when governments make appropriate interference are lowered compared to that without appropriate governments' interference. The results show the effectiveness of governments in preventing financial crises from the viewpoint of the negative information-propagation-induced model, namely governments' prevention against financial crises can reduce the possibility of the generation of financial crises.

Quantum transport in topological semimetals under magnetic fields

NASA Astrophysics Data System (ADS)

Lu, Hai-Zhou; Shen, Shun-Qing

2017-06-01

Topological semimetals are three-dimensional topological states of matter, in which the conduction and valence bands touch at a finite number of points, i.e., the Weyl nodes. Topological semimetals host paired monopoles and antimonopoles of Berry curvature at the Weyl nodes and topologically protected Fermi arcs at certain surfaces. We review our recent works on quantum transport in topological semimetals, according to the strength of the magnetic field. At weak magnetic fields, there are competitions between the positive magnetoresistivity induced by the weak anti-localization effect and negative magnetoresistivity related to the nontrivial Berry curvature. We propose a fitting formula for the magnetoconductivity of the weak anti-localization. We expect that the weak localization may be induced by inter-valley effects and interaction effect, and occur in double-Weyl semimetals. For the negative magnetoresistance induced by the nontrivial Berry curvature in topological semimetals, we show the dependence of the negative magnetoresistance on the carrier density. At strong magnetic fields, specifically, in the quantum limit, the magnetoconductivity depends on the type and range of the scattering potential of disorder. The high-field positive magnetoconductivity may not be a compelling signature of the chiral anomaly. For long-range Gaussian scattering potential and half filling, the magnetoconductivity can be linear in the quantum limit. A minimal conductivity is found at the Weyl nodes although the density of states vanishes there.

Oncolytic adenovirus encoding tumor necrosis factor-related apoptosis inducing ligand (TRAIL) inhibits the growth and metastasis of triple-negative breast cancer

PubMed Central

Zhu, Wei; Zhang, Hongwei; Shi, Yi; Song, Mangen; Zhu, Bijun; Wei, Lai

2013-01-01

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising cancer therapeutic target due to its selective apoptosis-inducing effect in cancer cells. To efficiently deliver TRAIL to the tumor cells, an oncolytic adenovirus (p55-hTERT-HRE-TRAIL) carrying the TRAIL coding sequence was constructed. In the present study, we aimed to investigate the effect of p55-hTERT-HRE-TRAIL on the growth and metastasis of triple-negative breast cancer (TNBC). We observed that infection of the recombinant adenovirus resulted in expression of TRAIL and massive cell death in a TNBC cell line MDA-MB-231. This effect is much weaker in MCF-10A, which is a normal breast cell line. Administration of P55-HTERT-HRE-TRAIL significantly reduced orthotopic breast tumor growth and extended survival in a metastatic model. Our results suggest the oncolytic adenovirus armed with P55-HTERT-HRE-TRAIL, which exhibited enhanced anti-tumor activity and improved survival, is a promising candidate for virotherapy of TNBC. PMID:24025362

Platelet-derived-growth-factor-induced signalling in human platelets: phosphoinositide-3-kinase-dependent inhibition of platelet activation.

PubMed Central

Selheim, F; Fukami, M H; Holmsen, H; Vassbotn, F S

2000-01-01

Human platelets release platelet-derived growth factor (PDGF) from alpha-granules during platelet activation. We have previously shown that platelets have PDGF alpha-receptors, a transmembrane tyrosine kinase that takes part in negative feedback regulation during platelet activation. Here we have described a study of PDGF-induced tyrosine phosphorylation of platelet substrates and phosphoinositide 3-kinase (PI-3K) activity in collagen-stimulated platelets. By immunoblotting with phosphotyrosine antibodies of collagen-activated platelets we found that PDGF increased the phosphorylation of several platelet substrates, e.g. pp140, pp120 and pp85. PDGF inhibited collagen-induced platelet activation in the presence of inhibitors of autocrine stimulation, thus blocking the pure collagen-induced signal transduction. PDGF enhanced the collagen-induced formation of PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3) as measured by HPLC. Wortmannin and LY294002, two unrelated inhibitors of PI-3K, were used to investigate the role of PI-3K in PDGF-induced platelet signalling. Incubation of platelets with wortmannin and LY294002 blocked the formation of three phosphorylated inositides as well as the inhibitory effect of PDGF on collagen-induced platelet activation. We conclude that the inhibitory effect of PDGF on platelet activation is PI-3K dependent. This is the first demonstration of a negative regulatory function of 3-phosphorylated inositides in platelets. PMID:10947961

Platelet-derived-growth-factor-induced signalling in human platelets: phosphoinositide-3-kinase-dependent inhibition of platelet activation.

PubMed

Selheim, F; Fukami, M H; Holmsen, H; Vassbotn, F S

2000-09-01

Human platelets release platelet-derived growth factor (PDGF) from alpha-granules during platelet activation. We have previously shown that platelets have PDGF alpha-receptors, a transmembrane tyrosine kinase that takes part in negative feedback regulation during platelet activation. Here we have described a study of PDGF-induced tyrosine phosphorylation of platelet substrates and phosphoinositide 3-kinase (PI-3K) activity in collagen-stimulated platelets. By immunoblotting with phosphotyrosine antibodies of collagen-activated platelets we found that PDGF increased the phosphorylation of several platelet substrates, e.g. pp140, pp120 and pp85. PDGF inhibited collagen-induced platelet activation in the presence of inhibitors of autocrine stimulation, thus blocking the pure collagen-induced signal transduction. PDGF enhanced the collagen-induced formation of PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3) as measured by HPLC. Wortmannin and LY294002, two unrelated inhibitors of PI-3K, were used to investigate the role of PI-3K in PDGF-induced platelet signalling. Incubation of platelets with wortmannin and LY294002 blocked the formation of three phosphorylated inositides as well as the inhibitory effect of PDGF on collagen-induced platelet activation. We conclude that the inhibitory effect of PDGF on platelet activation is PI-3K dependent. This is the first demonstration of a negative regulatory function of 3-phosphorylated inositides in platelets.

Degrading emotional memories induced by a virtual reality paradigm.

PubMed

Cuperus, Anne A; Laken, Maarten; van den Hout, Marcel A; Engelhard, Iris M

2016-09-01

In Eye Movement and Desensitization and Reprocessing (EMDR) therapy, a dual-task approach is used: patients make horizontal eye movements while they recall aversive memories. Studies showed that this reduces memory vividness and/or emotionality. A strong explanation is provided by working memory theory, which suggests that other taxing dual-tasks are also effective. Experiment 1 tested whether a visuospatial task which was carried out while participants were blindfolded taxes working memory. Experiment 2 tested whether this task degrades negative memories induced by a virtual reality (VR) paradigm. In experiment 1, participants responded to auditory cues with or without simultaneously carrying out the visuospatial task. In experiment 2, participants recalled negative memories induced by a VR paradigm. The experimental group simultaneously carried out the visuospatial task, and a control group merely recalled the memories. Changes in self-rated memory vividness and emotionality were measured. The slowing down of reaction times due to the visuospatial task indicated that its cognitive load was greater than the load of the eye movements task in previous studies. The task also led to reductions in emotionality (but not vividness) of memories induced by the VR paradigm. Weaknesses are that only males were tested in experiment 1, and the effectiveness of the VR fear/trauma induction was not assessed with ratings of mood or intrusions in experiment 2. The results suggest that the visuospatial task may be applicable in clinical settings, and the VR paradigm may provide a useful method of inducing negative memories. Copyright © 2016 Elsevier Ltd. All rights reserved.

Radotinib induces high cytotoxicity in c-KIT positive acute myeloid leukemia cells.

PubMed

Heo, Sook-Kyoung; Noh, Eui-Kyu; Kim, Jeong Yi; Jo, Jae-Cheol; Choi, Yunsuk; Koh, SuJin; Baek, Jin Ho; Min, Young Joo; Kim, Hawk

2017-06-05

Previously, we reported that radotinib, a BCR-ABL1 tyrosine kinase inhibitor, induced cytotoxicity in acute myeloid leukemia (AML) cells. However, the effects of radotinib in the subpopulation of c-KIT-positive AML cells were unclear. We observed that low-concentration radotinib had more potent cytotoxicity in c-KIT-positive cells than c-KIT-negative cells from AML patients. To address this issue, cell lines with high c-KIT expression, HEL92.1.7, and moderate c-KIT expression, H209, were selected. HEL92.1.7 cells were grouped into intermediate and high c-KIT expression populations. The cytotoxicity of radotinib against the HEL92.1.7 cell population with intermediate c-KIT expression was not different from that of the population with high c-KIT expression. When H209 cells were grouped into c-KIT expression-negative and c-KIT expression-positive populations, radotinib induced cytotoxicity in the c-KIT-positive population, but not the c-KIT-negative population. Thus, radotinib induces cytotoxicity in c-KIT-positive cells, regardless of the c-KIT expression intensity. Therefore, radotinib induces significant cytotoxicity in c-KIT-positive AML cells, suggesting that radotinib is a potential target agent for the treatment of c-KIT-positive malignancies including AML. Copyright © 2017 Elsevier B.V. All rights reserved.

[Exploration on Electroencephalogram Mechanism Differences of Negative Emotions Induced by Disgusted and Sad Situation Images].

PubMed

Wang, Xin; Jin, Jingna; Li, Song; Liu, Zhipeng; Yin, Tao

2015-12-01

Evolutionary psychology holds such an opinion that negative situation may threaten survival, trigger avoidance motive and have poor effects on the human-body function and the psychological quality. Both disgusted and sad situations can induce negative emotions. However, differences between the two situations on attention capture and emotion cognition during the emotion induction are still not well known. Typical disgusted and sad situation images were used in the present study to induce two negative emotions, and 15 young students (7 males and 8 females, aged 27 ± 3) were recruited in the experiments. Electroencephalogram of 32 leads was recorded when the subjects were viewing situation images, and event-related potentials (ERP) of all leads were obtained for future analysis. Paired sample t tests were carried out on two ERP signals separately induced by disgusted and sad situation images to get time quantum with significant statistical differences between the two ERP signals. Root-mean-square deviations of two ERP signals during each time quantum were calculated and the brain topographic map based on root-mean-square deviations was drawn to display differences of two ERP signals in spatial. Results showed that differences of ERP signals induced by disgusted and sad situation images were mainly manifested in T1 (120-450 ms) early and T2 (800-1,000 ms) later. During the period of T1, the occipital lobe reflecting attention capture was activated by both disgusted and sad situation images, but the prefrontal cortex reflecting emotion sense was activated only by disgusted situation images. During the period of T2, the prefrontal cortex was activated by both disgusted and sad situation images. However, the parietal lobe was activated only by disgusted situation images, which showed stronger emotional perception. The research results would have enlightenment to deepen understanding of negative emotion and to exploredeep cognitive neuroscience mechanisms of negative emotion induction.

Multisensory integration of speech sounds with letters vs. visual speech: only visual speech induces the mismatch negativity.

PubMed

Stekelenburg, Jeroen J; Keetels, Mirjam; Vroomen, Jean

2018-05-01

Numerous studies have demonstrated that the vision of lip movements can alter the perception of auditory speech syllables (McGurk effect). While there is ample evidence for integration of text and auditory speech, there are only a few studies on the orthographic equivalent of the McGurk effect. Here, we examined whether written text, like visual speech, can induce an illusory change in the perception of speech sounds on both the behavioural and neural levels. In a sound categorization task, we found that both text and visual speech changed the identity of speech sounds from an /aba/-/ada/ continuum, but the size of this audiovisual effect was considerably smaller for text than visual speech. To examine at which level in the information processing hierarchy these multisensory interactions occur, we recorded electroencephalography in an audiovisual mismatch negativity (MMN, a component of the event-related potential reflecting preattentive auditory change detection) paradigm in which deviant text or visual speech was used to induce an illusory change in a sequence of ambiguous sounds halfway between /aba/ and /ada/. We found that only deviant visual speech induced an MMN, but not deviant text, which induced a late P3-like positive potential. These results demonstrate that text has much weaker effects on sound processing than visual speech does, possibly because text has different biological roots than visual speech. © 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Blue light- and genetically-reversed gravitropic response in protonemata of the moss Ceratodon purpureus.

PubMed

Lamparter, T; Hughes, J; Hartmann, E

1998-09-01

In darkness, protonemal filaments of Ceratodon purpureus (Brid.) grow negatively gravitropically (upwards). Red light induces a positive phototropic response mediated by the photoreceptor phytochrome. A red light treatment also has an inhibitory effect on the gravitropic response, an effect also mediated by phytochrome. In this study the effects of blue light on phototropism and on gravitropism were analysed. Unilateral blue light resulted in only a weak phototropic response, but markedly randomised growth direction. Blue light given together with a gravitropic stimulus reversed the gravitropism, changing it from negative to positive (filaments grow downward). The effect of blue light was also analysed with the mutant ptr116, which is defective in the biosynthesis of the phytochrome chromophore, and in a newly isolated mutant wwr2, which is positively gravitropic in darkness. Blue light induced the same reversal of gravitropism in ptrll6 as in the wild type, indicating that phytochrome is not involved in this process. In wwr2 the direction of gravitropism was unaltered by the blue light treatment. Light also affects chlorophyll content and the size of plastids, potential statoliths for gravitropism. Red light induced an increase in plastid size and chlorophyll content in the wild type but not in ptr116. Blue light induced a similar change in wild type plastids. It seems as though light-induced alterations of gravitropism are not simply mediated by alterations in plastid properties, and that red light and blue light evoke fundamentally different responses.

Impact of oxidative stress on exercising skeletal muscle.

PubMed

Steinbacher, Peter; Eckl, Peter

2015-04-10

It is well established that muscle contractions during exercise lead to elevated levels of reactive oxygen species (ROS) in skeletal muscle. These highly reactive molecules have many deleterious effects, such as a reduction of force generation and increased muscle atrophy. Since the discovery of exercise-induced oxidative stress several decades ago, evidence has accumulated that ROS produced during exercise also have positive effects by influencing cellular processes that lead to increased expression of antioxidants. These molecules are particularly elevated in regularly exercising muscle to prevent the negative effects of ROS by neutralizing the free radicals. In addition, ROS also seem to be involved in the exercise-induced adaptation of the muscle phenotype. This review provides an overview of the evidences to date on the effects of ROS in exercising muscle. These aspects include the sources of ROS, their positive and negative cellular effects, the role of antioxidants, and the present evidence on ROS-dependent adaptations of muscle cells in response to physical exercise.

Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum.

PubMed

Lupia, Enrico; Spatola, Tiziana; Cuccurullo, Alessandra; Bosco, Ornella; Mariano, Filippo; Pucci, Angela; Ramella, Roberta; Alloatti, Giuseppe; Montrucchio, Giuseppe

2010-09-01

Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis. We showed the expression of the TPO receptor c-Mpl on myocardial cells and tissue by RT-PCR, immunofluorescence and western blotting. We then evaluated the effect of TPO on the contractile function of rat papillary muscle and isolated heart. TPO did not change myocardial contractility in basal conditions, but, when followed by epinephrine (EPI) stimulation, it blunted the enhancement of contractile force induced by EPI both in papillary muscle and isolated heart. An inhibitor of TPO prevented TPO effect on cardiac inotropy. Treatment of papillary muscle with pharmacological inhibitors of phosphatidylinositol 3-kinase, NO synthase, and guanilyl cyclase abolished TPO effect, indicating NO as the final mediator. We finally studied the role of TPO in the negative inotropic effect exerted by human septic shock (HSS) serum and TPO cooperation with TNF-alpha and IL-1beta. Pre-treatment with the TPO inhibitor prevented the decrease in contractile force induced by HSS serum. Moreover, TPO significantly amplified the negative inotropic effect induced by TNF-alpha and IL-1beta in papillary muscle. In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum.

Histone deacetylase inhibitor treatment induces ‘BRCAness’ and synergistic lethality with PARP inhibitor and cisplatin against human triple negative breast cancer cells

PubMed Central

Ha, Kyungsoo; Bhaskara, Srividya; Cerchietti, Leandro; Devaraj, Santhana G. T.; Shah, Bhavin; Sharma, Sunil; Chang, Jenny C.; Melnick, Ari M.; Hiebert, Scott; Bhalla, Kapil N.

2014-01-01

There is an unmet need to develop new, more effective and safe therapies for the aggressive forms of triple negative breast cancers (TNBCs). While up to 20% of women under 50 years of age with TNBC harbor germline mutations in BRCA1, and these tumors are sensitive to treatment with poly(ADP) ribose polymerase inhibitors, a majority of TNBCs lack BRCA1 mutations or loss of expression. Findings presented here demonstrate that by attenuating the levels of DNA damage response and homologous recombination proteins, pan-histone deacetylase inhibitor (HDI) treatment induces ‘BRCAness’ and sensitizes TNBC cells lacking BRCA1 to lethal effects of PARP inhibitor or cisplatin. Treatment with HDI also induced hyperacetylation of nuclear hsp90. Similar effects were observed following shRNA-mediated depletion of HDAC3, confirming its role as the deacetylase for nuclear HSP90. Furthermore, cotreatment with HDI and ABT-888 induced significantly more DNA strand breaks than either agent alone, and synergistically induced apoptosis of TNBC cells. Notably, co-treatment with HDI and ABT-888 significantly reduced in vivo tumor growth and markedly improved the survival of mice bearing TNBC cell xenografts. These findings support the rationale to interrogate the clinical activity of this novel combination against human TNBC, irrespective of its expression of mutant BRCA1. PMID:25026298

Negative differential resistance effect induced by metal ion implantation in SiO2 film for multilevel RRAM application

NASA Astrophysics Data System (ADS)

Wu, Facai; Si, Shuyao; Shi, Tuo; Zhao, Xiaolong; Liu, Qi; Liao, Lei; Lv, Hangbing; Long, Shibing; Liu, Ming

2018-02-01

Pt/SiO2:metal nanoparticles/Pt sandwich structure is fabricated with the method of metal ion (Ag) implantation. The device exhibits multilevel storage with appropriate R off/R on ratio, good endurance and retention properties. Based on transmission electron microscopy and energy dispersive spectrometer analysis, we confirm that Pt nanoparticles are spurted into SiO2 film from Pt bottom electrode by Ag implantation; during electroforming, the local electric field can be enhanced by these Pt nanoparticles, meanwhile the Ag nanoparticles constantly migrate toward the Pt nanoparticles. The implantation induced nanoparticles act as trap sites in the resistive switching layer and play critical roles in the multilevel storage, which is evidenced by the negative differential resistance effect in the current-voltage (I-V) measurements.

Profertility and antidiabetic properties of Gynura procumbens on streptozotocin induced male rats

NASA Astrophysics Data System (ADS)

Khaidatul Akmar, K.; Mahanem, M. N.

2016-11-01

Gynura procumbens (GP) is an herbal plant that is used for treating diseases such as diabetes mellitus, cardiovascular and also fertility. The objective of this study was to determine the anti-diabetic and pro-fertility effect of GP on streptozotocin induced male rats within 14 days. A total of 42 male rats were randomly assigned into six groups; normal, negative, and positive control, and three treated groups of different dosages of GP; 150 mg/kg, 300 mg/kg and 450 mg/kg. The treated groups were given aqueous extract GP via oral gavage for 14 consecutive days. The fasting blood glucose (FBG) level in all treated groups showed significant decreased compared to negative and positive group after 14 days treatment. Sperm quality parameters in GP treated group (450 mg/kg) showed significant increase when compared to negative and positive group. It was observed that the histology of testes in the treated group (450 mg/kg) produced a significant result whereby the germinal cell layer shown an arranged order of cells compared to the negative and positive control groups. It appeared that aqueous extract of GP have a pro-fertility effect and possess anti-hyperglycemic activity within 14 days of treatment.

The asymmetrical force of persuasive knowledge across the positive-negative divide.

PubMed

Nordmo, Mads; Selart, Marcus

2015-01-01

In two experimental studies we explore to what extent the general effects of positive and negative framing also apply to positive and negative persuasion. Our results reveal that negative persuasion induces substantially higher levels of skepticism and awareness of being subjected to a persuasion attempt. Furthermore, we demonstrate that in positive persuasion, more claims lead to stronger persuasion, while in negative persuasion, the numerosity of claims carries no significant effect. We interpret this finding along the lines of a satiety-model of persuasion. Finally, using diluted, or low strength claims in a persuasion attempt, we reveal a significant interaction between dispositional reactance and dilution of claims on persuasion knowledge. The interaction states that diluted claims increase the awareness of being subjected to a persuasion attempt, but only for those with a high dispositional level of reactance.

The asymmetrical force of persuasive knowledge across the positive–negative divide

PubMed Central

Nordmo, Mads; Selart, Marcus

2015-01-01

In two experimental studies we explore to what extent the general effects of positive and negative framing also apply to positive and negative persuasion. Our results reveal that negative persuasion induces substantially higher levels of skepticism and awareness of being subjected to a persuasion attempt. Furthermore, we demonstrate that in positive persuasion, more claims lead to stronger persuasion, while in negative persuasion, the numerosity of claims carries no significant effect. We interpret this finding along the lines of a satiety-model of persuasion. Finally, using diluted, or low strength claims in a persuasion attempt, we reveal a significant interaction between dispositional reactance and dilution of claims on persuasion knowledge. The interaction states that diluted claims increase the awareness of being subjected to a persuasion attempt, but only for those with a high dispositional level of reactance. PMID:26388821

Nonlinear Magnus-induced dynamics and Shapiro spikes for ac and dc driven skyrmions on periodic quasi-one-dimensional substrates

NASA Astrophysics Data System (ADS)

Reichhardt, Charles; Reichhardt, Cynthia J. Olson

We numerically examine skyrmions interacting with a periodic quasi-one-dimensional substrate. When we drive the skyrmions perpendicular to the substrate periodicity direction, a rich variety of nonlinear Magnus-induced effects arise, in contrast to an overdamped system that shows only a linear velocity-force curve for this geometry. The skyrmion velocity-force curve is strongly nonlinear and we observe a Magnus-induced speed-up effect when the pinning causes the Magnus velocity response to align with the dissipative response. At higher applied drives these components decouple, resulting in strong negative differential conductivity. For skyrmions under combined ac and dc driving, we find a new class of phase locking phenomena in which the velocity-force curves contain a series of what we call Shapiro spikes, distinct from the Shapiro steps observed in overdamped systems. There are also regimes in which the skyrmion moves in the direction opposite to the applied dc drive to give negative mobility.

Hypoxia Worsens Affective Responses and Feeling of Fatigue During Prolonged Bed Rest

PubMed Central

Stavrou, Nektarios A. M.; Debevec, Tadej; Eiken, Ola; Mekjavic, Igor B.

2018-01-01

Previous research, although limited, suggests that both hypoxia and bed rest influence psychological responses by exaggerating negative psychological responses and attenuating positive emotions. The present study investigated the effect of a 21-day prolonged exposure to normobaric hypoxia and bed rest on affective responses and fatigue. Eleven healthy participants underwent three 21-day interventions using a cross-over design: (1) normobaric hypoxic ambulatory confinement (HAMB), (2) normobaric hypoxic bed rest (HBR) and (3) normoxic bed rest (NBR). Affective and fatigue responses were investigated using the Activation Deactivation Adjective Check List, and the Multidimensional Fatigue Inventory, which were completed before (Pre), during (Day 7, Day 14, and Day 21) and after (Post) the interventions. The most negative psychological profile appeared during the HBR intervention. Specifically, tiredness, tension, general and physical fatigue significantly increased on days 7, 14, and 21, as well as at Post. After the HBR intervention, general and physical fatigue remained higher compared to Pre values. Additionally, a deterioration of psychological responses was also noted following HAMB and NBR. In particular, both hypoxia and BR per se induced subjective fatigue and negative affective responses. BR seems to exert a moderate negative effect on the sensation of fatigue, whereas exercise attenuates the negative effects of hypoxia as noted during the HAMB condition. In conclusion, our data suggest that the addition of hypoxia to bed rest-induced inactivity significantly worsens affective responses and feeling of fatigue. PMID:29628903

OP16, a novel ent-kaurene diterpenoid, potentiates the antitumor effect of rapamycin by inhibiting rapamycin-induced feedback activation of Akt signaling in esophageal squamous cell carcinoma.

PubMed

Peng, Ke-Zheng; Ke, Yu; Zhao, Qi; Tian, Fei; Liu, Hong-Min; Hou, Guiqin; Lu, Zhaoming

2017-09-15

Hyperactivation of mTOR signaling pathway has been viewed as a significant molecular pathogenesis of cancer. However, inhibition of mTOR by rapamycin and its analogs could induce numerous negative feedback loops to attenuate their therapeutic efficacy. As a traditional Chinese herbal medicine, Rabdosia rubescens has been used to treat esophageal squamous cell carcinoma (ESCC) for hundreds of years, and its major effective component is oridonin. Here we reported that OP16, a novel analog of oridonin, showed potent inhibition of cell proliferation and Akt phosphorylation in ESCC cells. The combination of OP16 and rapamycin possesses synergistic anti-proliferative and pro-apoptotic effects both in ESCC cells and ESCC xenografts, and no obvious adverse effect was observed in vivo. Mechanistic analysis revealed that OP16 could inhibit rapamycin-induced Akt activation through the p70S6K-mediated negative feedback loops, and the combination of OP16 and rapamycin was more effective in activating caspase-dependent apoptotic signaling cascade. This study supports the combined use of OP16 with rapamycin as a feasible and effective therapeutic approach for future treatment of ESCC. Copyright © 2017 Elsevier Inc. All rights reserved.

UVB Induces a Genome-Wide Acting Negative Regulatory Mechanism That Operates at the Level of Transcription Initiation in Human Cells

PubMed Central

Gyenis, Ákos; Umlauf, David; Újfaludi, Zsuzsanna; Boros, Imre; Ye, Tao; Tora, Làszlò

2014-01-01

Faithful transcription of DNA is constantly threatened by different endogenous and environmental genotoxic effects. Transcription coupled repair (TCR) has been described to stop transcription and quickly remove DNA lesions from the transcribed strand of active genes, permitting rapid resumption of blocked transcription. This repair mechanism has been well characterized in the past using individual target genes. Moreover, numerous efforts investigated the fate of blocked RNA polymerase II (Pol II) during DNA repair mechanisms and suggested that stopped Pol II complexes can either backtrack, be removed and degraded or bypass the lesions to allow TCR. We investigated the effect of a non-lethal dose of UVB on global DNA-bound Pol II distribution in human cells. We found that the used UVB dose did not induce Pol II degradation however surprisingly at about 93% of the promoters of all expressed genes Pol II occupancy was seriously reduced 2–4 hours following UVB irradiation. The presence of Pol II at these cleared promoters was restored 5–6 hours after irradiation, indicating that the negative regulation is very dynamic. We also identified a small set of genes (including several p53 regulated genes), where the UVB-induced Pol II clearing did not operate. Interestingly, at promoters, where Pol II promoter clearance occurs, TFIIH, but not TBP, follows the behavior of Pol II, suggesting that at these genes upon UVB treatment TFIIH is sequestered for DNA repair by the TCR machinery. In agreement, in cells where the TCR factor, the Cockayne Syndrome B protein, was depleted UVB did not induce Pol II and TFIIH clearance at promoters. Thus, our study reveals a UVB induced negative regulatory mechanism that targets Pol II transcription initiation on the large majority of transcribed gene promoters, and a small subset of genes, where Pol II escapes this negative regulation. PMID:25058334

Cr doping induced negative transverse magnetoresistance in C d3A s2 thin films

NASA Astrophysics Data System (ADS)

Liu, Yanwen; Tiwari, Rajarshi; Narayan, Awadhesh; Jin, Zhao; Yuan, Xiang; Zhang, Cheng; Chen, Feng; Li, Liang; Xia, Zhengcai; Sanvito, Stefano; Zhou, Peng; Xiu, Faxian

2018-02-01

The magnetoresistance of a material conveys various dynamic information about charge and spin carriers, inspiring both fundamental studies in physics and practical applications such as magnetic sensors, data storage, and spintronic devices. Magnetic impurities play a crucial role in the magnetoresistance as they induce exotic states of matter such as the quantum anomalous Hall effect in topological insulators and tunable ferromagnetic phases in dilute magnetic semiconductors. However, magnetically doped topological Dirac semimetals are hitherto lacking. Here, we report a systematic study of Cr-doped C d3A s2 thin films grown by molecular-beam epitaxy. With the Cr doping, C d3A s2 thin films exhibit unexpected negative transverse magnetoresistance and strong quantum oscillations, bearing a trivial Berry's phase and an enhanced effective mass. More importantly, with ionic gating the magnetoresistance of Cr-doped C d3A s2 thin films can be drastically tuned from negative to positive, demonstrating the strong correlation between electrons and the localized spins of the Cr impurities, which we interpret through the formation of magnetic polarons. Such a negative magnetoresistance under perpendicular magnetic field and its gate tunability have not been observed previously in the Dirac semimetal C d3A s2 . The Cr-induced topological phase transition and the formation of magnetic polarons in C d3A s2 provide insights into the magnetic interaction in Dirac semimetals as well as their potential applications in spintronics.

The effects of aging on emotion-induced modulations of source retrieval ERPs: evidence for valence biases.

PubMed

Newsome, Rachel N; Dulas, Michael R; Duarte, Audrey

2012-12-01

Many behavioral studies have shown that memory is enhanced for emotionally salient events across the lifespan. It has been suggested that this mnemonic boost may be observed for both age groups, particularly the old, in part because emotional information is retrieved with less effort than neutral information. Neuroimaging evidence suggests that inefficient retrieval processing (temporally delayed and attenuated) may contribute to age-related impairments in episodic memory for neutral events. It is not entirely clear whether emotional salience may reduce these age-related changes in neural activity associated with episodic retrieval for neutral events. Here, we investigated these ideas using event-related potentials (ERPs) to assess the neural correlates of successful source memory retrieval ("old-new effects") for neutral and emotional (negative and positive) images. Behavioral results showed that older adults demonstrated source memory impairments compared to the young but that both groups showed reduced source memory accuracy for negative compared to positive and neutral images; most likely due to an arousal-induced memory tradeoff for the negative images, which were subjectively more arousing than both positive and neutral images. ERP results showed that early onsetting old-new effects, between 100 and 300 ms, were observed for emotional but not neutral images in both age groups. Interestingly, these early effects were observed for negative items in the young and for positive items in the old. These ERP findings offer support for the idea that emotional events may be retrieved more automatically than neutral events across the lifespan. Furthermore, we suggest that very early retrieval mechanisms, possibly perceptual priming or familiarity, may underlie the negativity and positivity effects sometimes observed in the young and old, respectively, for various behavioral measures of attention and memory. Copyright © 2012 Elsevier Ltd. All rights reserved.

Magnetic field effect on pentacene-doped sexithiophene diodes

NASA Astrophysics Data System (ADS)

Pham, Song-Toan; Fayolle, Marine; Ohto, Tatsuhiko; Tada, Hirokazu

2017-11-01

We studied the effect of impurities on the magnetoresistance of sexithiophene-based diodes using impedance spectroscopy. The impurities were introduced by doping pentacene molecules into a sexithiophene film through a co-evaporation process. The pentacene molecules act as charge-scattering centers, which trigger the negative magnetoresistance of the device. This makes it possible to tune the value of magnetoresistance from positive to negative by increasing the applied voltage. The beneficial properties induced by impurities suggest a potential route to integrate additional functions into organic devices.

Acute Effects of Capsaicin on Energy Expenditure and Fat Oxidation in Negative Energy Balance

PubMed Central

Janssens, Pilou L. H. R.; Hursel, Rick; Martens, Eveline A. P.; Westerterp-Plantenga, Margriet S.

2013-01-01

Background Addition of capsaicin (CAPS) to the diet has been shown to increase energy expenditure; therefore capsaicin is an interesting target for anti-obesity therapy. Aim We investigated the 24 h effects of CAPS on energy expenditure, substrate oxidation and blood pressure during 25% negative energy balance. Methods Subjects underwent four 36 h sessions in a respiration chamber for measurements of energy expenditure, substrate oxidation and blood pressure. They received 100% or 75% of their daily energy requirements in the conditions ‘100%CAPS’, ‘100%Control’, ‘75%CAPS’ and ‘75%Control’. CAPS was given at a dose of 2.56 mg (1.03 g of red chili pepper, 39,050 Scoville heat units (SHU)) with every meal. Results An induced negative energy balance of 25% was effectively a 20.5% negative energy balance due to adapting mechanisms. Diet-induced thermogenesis (DIT) and resting energy expenditure (REE) at 75%CAPS did not differ from DIT and REE at 100%Control, while at 75%Control these tended to be or were lower than at 100%Control (p = 0.05 and p = 0.02 respectively). Sleeping metabolic rate (SMR) at 75%CAPS did not differ from SMR at 100%CAPS, while SMR at 75%Control was lower than at 100%CAPS (p = 0.04). Fat oxidation at 75%CAPS was higher than at 100%Control (p = 0.03), while with 75%Control it did not differ from 100%Control. Respiratory quotient (RQ) was more decreased at 75%CAPS (p = 0.04) than at 75%Control (p = 0.05) when compared with 100%Control. Blood pressure did not differ between the four conditions. Conclusion In an effectively 20.5% negative energy balance, consumption of 2.56 mg capsaicin per meal supports negative energy balance by counteracting the unfavorable negative energy balance effect of decrease in components of energy expenditure. Moreover, consumption of 2.56 mg capsaicin per meal promotes fat oxidation in negative energy balance and does not increase blood pressure significantly. Trial Registration Nederlands Trial Register; registration number NTR2944 PMID:23844093

Anti-apoptotic effect of phloretin on cisplatin-induced apoptosis in HEI-OC1 auditory cells.

PubMed

Choi, Byung-Min; Chen, Xiao Yan; Gao, Shang Shang; Zhu, Rizhe; Kim, Bok-Ryang

2011-01-01

Cisplatin is a highly effective chemotherapeutic agent, but it has significant ototoxic side effects. Apoptosis is an important mechanism of cochlear hair cell loss following exposure to cisplatin. The present study examined the effects of phloretin, a natural polyphenolic compound found in apples and pears, on cisplatin-induced apoptosis. We found that phloretin induced the expression of heme oxygenase-1 (HO-1) protein in a concentration- and time-dependent manner. Phloretin induced nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation, and dominant-negative Nrf2 attenuated phloretin-induced expression of HO-1. Phloretin activated the JNK, ERK and p38 mitogen-activated protein kinase (MAPK) pathways, and the JNK pathway played an important role in phloretin-induced HO-1 expression. Phloretin protected the cells against cisplatin-induced apoptosis. The protective effect of phloretin was abrogated by zinc protoporphyrin IX (ZnPP IX), a HO inhibitor. Furthermore, phloretin pretreatment inhibited mitochondrial dysfunction and the activation of caspases. These results demonstrate that the expression of HO-1 induced by phloretin is mediated by both the JNK pathway and Nrf2; the expression inhibits cisplatin-induced apoptosis in HEI-OC1 cells.

Mindfulness and emotion regulation—an fMRI study

PubMed Central

Lutz, Jacqueline; Herwig, Uwe; Opialla, Sarah; Hittmeyer, Anna; Jäncke, Lutz; Rufer, Michael; Grosse Holtforth, Martin

2014-01-01

Mindfulness—an attentive non-judgmental focus on present experiences—is increasingly incorporated in psychotherapeutic treatments as a skill fostering emotion regulation. Neurobiological mechanisms of actively induced emotion regulation are associated with prefrontally mediated down-regulation of, for instance, the amygdala. We were interested in neurobiological correlates of a short mindfulness instruction during emotional arousal. Using functional magnetic resonance imaging, we investigated effects of a short mindfulness intervention during the cued expectation and perception of negative and potentially negative pictures (50% probability) in 24 healthy individuals compared to 22 controls. The mindfulness intervention was associated with increased activations in prefrontal regions during the expectation of negative and potentially negative pictures compared to controls. During the perception of negative stimuli, reduced activation was identified in regions involved in emotion processing (amygdala, parahippocampal gyrus). Prefrontal and right insular activations when expecting negative pictures correlated negatively with trait mindfulness, suggesting that more mindful individuals required less regulatory resources to attenuate emotional arousal. Our findings suggest emotion regulatory effects of a short mindfulness intervention on a neurobiological level. PMID:23563850

Lycopene Protects Keratinocytes Against UVB Radiation-Induced Carcinogenesis via Negative Regulation of FOXO3a Through the mTORC2/AKT Signaling Pathway.

PubMed

Chen, Ping; Xu, Shina; Qu, Jinlong

2018-01-01

Lycopene, one of the most potent anti-oxidants, has been reported to exhibit potent anti-proliferative properties in a wide range of cancer cells through modulation of the cell cycle and apoptosis. Forkhead box O3 (FOXO3a) plays a pivotal role in modulating the expression of genes involved in cell death. Herein, we investigated the role of FOXO3a signaling in the anti-cancer effects of lycopene. Results showed that lycopene pretreatment attenuated UVB-induced cell hyper-proliferation and promoted apoptosis, accompanied by decreased cyclin-dependent kinase 2 (CDK2) and CDK4 complex in both human keratinocytes and SKH-1 hairless mice. FOXO3a is phosphorylated in response to UVB irradiation and sequestered in the cytoplasm, while lycopene pretreatment rescued this sensitization. Gene ablation of FOXO3a attenuated lycopene-induced decrease in cell hyper-proliferation, CDK2, and CDK4 complex, indicating a critical role of FOXO3a in the lycopene-induced anti-proliferative effect of keratinocytes during UVB irradiation. Transfection with FOXO3a siRNA inhibited the lycopene-induced increase in cell apoptosis, BAX and cleaved PARP expression. Moreover, loss of AKT induced further accelerated lycopene-induced FOXO3a dephosphorylation, while loss of mechanistic target of rapamycin complex 2 (mTORC2) by transfection with RICTOR siRNA induced levels of AKT phosphorylation comparable to those obtained with lycopene. In contrast, overexpression of AKT or mTORC2 decreased the effects of lycopene on the expression of FOXO3a as well as AKT phosphorylation, suggesting that lycopene depends on the negative modulation of mTORC2/AKT signaling. Taken together, our findings demonstrate that the mTORC2/AKT/FOXO3a axis plays a critical role in the anti-proliferative and pro-apoptotic effects of lycopene in UVB-induced photocarcinogenesis. J. Cell. Biochem. 119: 366-377, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

AID downregulation is a novel function of the DNMT inhibitor 5-aza-deoxycytidine

PubMed Central

Tsai, Chiou-Tsun; Yang, Pei-Ming; Chern, Ting-Rong; Chuang, Shu-Hui; Lin, Jung-Hsin; Klemm, Lars; Müschen, Markus; Chen, Ching-Chow

2014-01-01

Activation-induced cytidine deaminase (AID) was originally identified as an inducer of somatic hypermutation (SHM) and class switch recombination (CSR) in immunoglobulin genes. However, AID can also cause mutations in host genes and contribute to cancer progression and drug resistance. In this study, molecular docking showed the interaction of free 5-aza-CdR and Zebularine (Zeb) with AID. However, only 5-aza-CdR-incorporated ssDNA bound to the active site of AID and inhibited AID expression through proteasomal degradation. 5-aza-CdR demonstrated cytotoxicity against AID-positive and -negative hematopoietic cancer cells. In contrast, Zeb exhibited a cytotoxic effect only in AID-negative cells due to its inability to inhibit AID expression. This differential effect might be due to the DNMT1 stabilization induced by AID, thus restricting the ability of Zeb to deplete DNMT1 and induce tumor suppressor genes (TSGs), such as p21, in AID-positive cells. Moreover, the in vivo anticancer effect of 5-aza-CdR but not Zeb in AID-positive hematopoietic cancer cells was demonstrated. The study not only displays the association of AID and DNMT1 and identifies a novel biological function of AID, but also provides novel information regarding the use of DNMT inhibitors to treat AID-positive hematopoietic cancers. PMID:24457556

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

You, Guoxiang

The extended DLVO (XDLVO) theory was applied to elucidate the potential effects of CeO{sub 2} nanoparticles (CeO{sub 2} NPs) on sludge aggregation and the role of extracellular polymeric substances (EPS). In this study, seven different concentrations of CeO{sub 2} NPs were added to activated sludge cultured in sequencing batch reactors (SBRs) and compared with a control test that received no CeO{sub 2} NPs. After exposure to 50 mg/L CeO{sub 2} NPs, a negligible change (p>0.1) occurred in the sludge volume index (SVI), whereas the flocculability and aggregation of the sludge decreased by 18.8% and 11.2%, respectively, resulting in a highmore » effluent turbidity. The XDLVO theory demonstrated that the adverse effects of the CeO{sub 2} NPs on sludge aggregation were due to an enhanced barrier energy. Compared to the van der Waals energies (W{sub A}) and the electric double layer (W{sub R}), the acid-base interaction (W{sub AB}) markedly changed for the various concentrations of CeO{sub 2} NPs. The EPS played a decisive role in the sludge surface characteristics, as the removal of EPS equals to the negative effects induced by 5–10 mg/L CeO{sub 2} NPs on the sludge flocculability and aggregation. The presence of CeO{sub 2} NPs induced negative contributions to the tight boundary EPS (TB-EPS) and core bacteria while positive contributions to the total interaction energy of the loose boundary EPS (LB-EPS). - Highlights: • CeO{sub 2} NPs adversely affected the flocculability and aggregation of the sludge. • The presence of CeO{sub 2} NPs increased the energy barrier and led to a stable suspension. • The removal of EPS equals to the negative effects induced by 5–10 mg/L CeO{sub 2} NPs. • The acid-base interaction was dominate and markedly changed for the CeO{sub 2} NPs. • CeO{sub 2} NPs induced negative contributions to the TB-EPS while positive to the LB-EPS.« less

Negative and positive magnetoresistance in GaInNAs/GaAs modulation-doped quantum well structures

NASA Astrophysics Data System (ADS)

Nutku, Ferhat; Donmez, Omer; Sarcan, Fahrettin; Erol, Ayşe; Puustinen, Janne; Arıkan, Mehmet Çetin; Guina, Mircea

2015-03-01

In this work, magnetoresistance of as-grown and annealed n- and p-type modulation-doped Ga0.68In0.32NyAs1-y/GaAs single quantum well structures with various nitrogen concentrations has been studied. At low temperatures and low magnetic fields, in n-type samples negative and in p-type samples positive, magnetoresistance has been observed. The observed negative magnetoresistance in n-type samples is an indication of enhanced backscattering of electrons due to the weak localization of the electrons as an effect of the N-induced defects. Nitrogen concentration and thermal annealing dependence of the magnetoresistance have been studied for both n- and p-type samples. The observed decrease in the negative magnetoresistance in n-type and enhanced positive magnetoresistance in p-type samples following thermal annealing have been explained by considering thermal annealing-induced improvement of mobility and the crystal quality in N-containing samples. After thermal annealing, the magnitude of negative magnetoresistance decreases and the breaking of the weak localization is achieved at lower magnetic fields in n-type samples. It is observed that as the mobility of the sample increases, critical magnetic field of negative to positive magnetoresistance transition becomes lower.

Cyproterone acetate enhances TRAIL-induced androgen-independent prostate cancer cell apoptosis via up-regulation of death receptor 5.

PubMed

Chen, Linjie; Wolff, Dennis W; Xie, Yan; Lin, Ming-Fong; Tu, Yaping

2017-03-07

Virtually all prostate cancer deaths occur due to obtaining the castration-resistant phenotype after prostate cancer cells escaped from apoptosis and/or growth suppression initially induced by androgen receptor blockade. TNF-related apoptosis-inducing ligand (TRAIL) was an attractive cancer therapeutic agent due to its minimal toxicity to normal cells and remarkable apoptotic activity in tumor cells. However, most localized cancers including prostate cancer are resistant to TRAIL-induced apoptosis, thereby creating a therapeutic challenge of inducing TRAIL sensitivity in cancer cells. Herein the effects of cyproterone acetate, an antiandrogen steroid, on the TRAIL-induced apoptosis of androgen receptor-negative prostate cancer cells are reported. Cell apoptosis was assessed by both annexin V/propidium iodide labeling and poly (ADP-ribose) polymerase cleavage assays. Gene and protein expression changes were determined by quantitative real-time PCR and western blot assays. The effect of cyproterone acetate on gene promoter activity was determined by luciferase reporter assay. Cyproterone acetate but not AR antagonist bicalutamide dramatically increased the susceptibility of androgen receptor-negative human prostate cancer PC-3 and DU145 cells to TRAIL-induced apoptosis but no effects on immortalized human prostate stromal PS30 cells and human embryonic kidney HEK293 cells. Further investigation of the TRAIL-induced apoptosis pathway revealed that cyproterone acetate exerted its effect by selectively increasing death receptor 5 (DR5) mRNA and protein expression. Cyproterone acetate treatment also increased DR5 gene promoter activity, which could be abolished by mutation of a consensus binding domain of transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP) in the DR5 gene promoter. Cyproterone acetate increases CHOP expression in a concentration and time-dependent manner and endoplasmic reticulum stress reducer 4-phenylbutyrate could block cyproterone acetate-induced CHOP and DR5 up-regulation. More importantly, siRNA silencing of CHOP significantly reduced cyproterone acetate-induced DR5 up-regulation and TRAIL sensitivity in prostate cancer cells. Our study shows a novel effect of cyproterone acetate on apoptosis pathways in prostate cancer cells and raises the possibility that a combination of TRAIL with cyproterone acetate could be a promising strategy for treating castration-resistant prostate cancer.

Nicotine withdrawal modulates frontal brain function during an affective Stroop task

PubMed Central

Modlin, Leslie; Wang, Lihong; Kozink, Rachel V.; McClernon, F. Joseph

2013-01-01

Background Among nicotine-dependent smokers, smoking abstinence disrupts multiple cognitive and affective processes including conflict resolution and emotional information processing (EIP). However, the neurobiological basis of abstinence effects on resolving emotional interference on cognition remains largely uncharacterized. In this study, functional magnetic resonance imaging (fMRI) was used to investigate smoking abstinence effects on emotion–cognition interactions. Methods Smokers (n=17) underwent fMRI while performing an affective Stroop task (aST) over two sessions: once following 24-h abstinence and once following smoking as usual. The aST includes trials that serially present incongruent or congruent numerical grids bracketed by neutral or negative emotional distractors and view-only emotional image trials. Statistical analyses were conducted using a statistical threshold of p<0.05 cluster corrected. Results Smoking abstinence increased Stroop blood-oxygenation-level-dependent response in the right middle frontal and rostral anterior cingulate gyri. Moreover, withdrawal-induced negative affect was associated with less activation in frontoparietal regions during negative emotional information processing; whereas, during Stroop trials, negative affect predicted greater activation in frontal regions during negative, but not neutral emotional distractor trials. Conclusion Hyperactivation in the frontal executive control network during smoking abstinence may represent a need to recruit additional executive resources to meet task demands. Moreover, abstinence-induced negative affect may disrupt cognitive control neural circuitry during EIP and place additional demands on frontal executive neural resources during cognitive demands when presented with emotionally distracting stimuli. PMID:21989805

Rapid negative inotropic effect induced by TNF-α in rat heart perfused related to PKC activation.

PubMed

Jude, B; Vetel, S; Giroux-Metges, M A; Pennec, J P

2018-07-01

Myocardial depression, frequently observed in septic shock, is mediated by circulating molecules such as cytokines. TNF-α appears to be the most important pro-inflammatory cytokine released during the early phase of a septic shock. It was previously shown that TNF-α had a negative inotropic effect on myocardium. Now, the aim of this study was to investigate the effects of the activation of PKC by TNF-α on heart function, and to determine if this cytokine could induce a decrease of membrane excitability. Isolated rat hearts (n = 6) were perfused with Tyrode solution containing TNF-α at 20 ng/ml during 30 min by using a Langendorff technique. Expressions of PKC-α and PKC-ε were analysed by western blot on membrane and cytosol proteins extracted from ventricular myocardium. Patch clamp was performed on freshly isolated cardiomyocytes (n = 8). Compared to control situation, 30 min of TNF-α perfusion led to cardiac dysfunction with a decrease of the heart rate (-83%), the force (-20%) and speed of relaxation (-18%) and the coronary flow (-25%). This is associated with an activation and a membrane targeting of both PKC-α and PKC-ε isoforms in ventricle with respectively +123% and +54% compared to control hearts. Nevertheless, TNF-α had no significant effect on voltage-gated sodium current (109.0%+/- 12.5) after addition of the cytokine when compared to control. These results showed that TNF-α had a negative inotropic effect on the isolated rat heart and can induce PKC activation leading to an impaired contractility of the heart. However the early heart dysfunction induced by the cytokine was not associated to a decrease of cardiomyocytes membrane excitability as it has been evidenced in skeletal muscle fibres. Copyright © 2017 Elsevier Ltd. All rights reserved.

Combinatorial Effects of Lapatinib and Rapamycin in Triple-Negative Breast Cancer Cells

PubMed Central

Liu, Tongrui; Yacoub, Rami; Taliaferro-Smith, LaTonia D.; Sun, Shi-Yong; Graham, Tisheeka R.; Dolan, Ryan; Lobo, Christine; Tighiouart, Mourad; Yang, Lily; Adams, Amy; O'Regan, Ruth M.

2016-01-01

Triple-negative breast cancers, which lack estrogen receptor, progesterone receptor, and HER2/neu overexpression, account for approximately 15% of breast cancers, but occur more commonly in African Americans. The poor survival outcomes seen with triple-negative breast cancers patients are, in part, due to a lack of therapeutic targets. Epidermal growth factor receptor (EGFR) is overexpressed in 50% of triple-negative breast cancers, but EGFR inhibitors have not been effective in patients with metastatic breast cancers. However, mTOR inhibition has been shown to reverse resistance to EGFR inhibitors. We examined the combination effects of mTOR inhibition with EGFR inhibition in triple-negative breast cancer in vitro and in vivo. The combination of EGFR inhibition by using lapatinib and mTOR inhibition with rapamycin resulted in significantly greater cytotoxicity than the single agents alone and these effects were synergistic in vitro. The combination of rapamycin and lapatinib significantly decreased growth of triple-negative breast cancers in vivo compared with either agent alone. EGFR inhibition abrogated the expression of rapamycin-induced activated Akt in triple-negative breast cancer cells in vitro. The combination of EGFR and mTOR inhibition resulted in increased apoptosis in some, but not all, triple-negative cell lines, and these apoptotic effects correlated with a decrease in activated eukaryotic translation initiation factor (eIF4E). These results suggest that mTOR inhibitors could sensitize a subset of triple-negative breast cancers to EGFR inhibitors. Given the paucity of effective targeted agents in triple-negative breast cancers, these results warrant further evaluation. PMID:21690228

The affective regulation of cognitive priming.

PubMed

Storbeck, Justin; Clore, Gerald L

2008-04-01

Semantic and affective priming are classic effects observed in cognitive and social psychology, respectively. The authors discovered that affect regulates such priming effects. In Experiment 1, positive and negative moods were induced before one of three priming tasks; evaluation, categorization, or lexical decision. As predicted, positive affect led to both affective priming (evaluation task) and semantic priming (category and lexical decision tasks). However, negative affect inhibited such effects. In Experiment 2, participants in their natural affective state completed the same priming tasks as in Experiment 1. As expected, affective priming (evaluation task) and category priming (categorization and lexical decision tasks) were observed in such resting affective states. Hence, the authors conclude that negative affect inhibits semantic and affective priming. These results support recent theoretical models, which suggest that positive affect promotes associations among strong and weak concepts, and that negative affect impairs such associations (Clore & Storbeck, 2006; Kuhl, 2000). (Copyright) 2008 APA.

Bardoxolone methyl prevents obesity and hypothalamic dysfunction.

PubMed

Camer, Danielle; Yu, Yinghua; Szabo, Alexander; Wang, Hongqin; Dinh, Chi H L; Huang, Xu-Feng

2016-08-25

High-fat (HF) diet-induced obesity is associated with hypothalamic leptin resistance and low grade chronic inflammation, which largely impairs the neuroregulation of negative energy balance. Neuroregulation of negative energy balance is largely controlled by the mediobasal and paraventricular nuclei regions of the hypothalamus via leptin signal transduction. Recently, a derivative of oleanolic acid, bardoxolone methyl (BM), has been shown to have anti-inflammatory effects. We tested the hypothesis that BM would prevent HF diet-induced obesity, hypothalamic leptin resistance, and inflammation in mice fed a HF diet. Oral administration of BM via drinking water (10 mg/kg daily) for 21 weeks significantly prevented an increase in body weight, energy intake, hyperleptinemia, and peripheral fat accumulation in mice fed a HF diet. Furthermore, BM treatment prevented HF diet-induced decreases in the anorexigenic effects of peripheral leptin administration. In the mediobasal and paraventricular nuclei regions of the hypothalamus, BM administration prevented HF diet-induced impairments of the downstream protein kinase b (Akt) pathway of hypothalamic leptin signalling. BM treatment also prevented an increase in inflammatory cytokines, tumour necrosis factor alpha (TNFα) and interleukin 6 (IL-6) in these two hypothalamic regions. These results identify a potential novel neuropharmacological application for BM in preventing HF diet-induced obesity, hypothalamic leptin resistance, and inflammation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Assessment of Risk Factors of Intrauterine Adhesions in Patients With Induced Abortion and the Curative Effect of Hysteroscopic Surgery.

PubMed

Mo, Xiaoliang; Qin, Guirong; Zhou, Zhoulin; Jiang, Xiaoli

2017-10-03

To explore the risk factors for intrauterine adhesions in patients with artificial abortion and clinical efficacy of hysteroscopic dissection. 1500 patients undergoing artificial abortion between January 2014 and June 2015 were enrolled into this study. The patients were divided into two groups with or without intrauterine adhesions. Univariate and Multiple logistic regression were conducted to assess the effects of multiple factors on the development of intrauterine adhesions following induced abortion. The incidence rate for intrauterine adhesions following induced abortion is 17.0%. Univariate showed that preoperative inflammation, multiple pregnancies and suction evacuation time are the influence risk factors of intrauterine adhesions. Multiple logistic regression demonstrates that multiple pregnancies, high intrauterine negative pressure, and long suction evacuation time are independent risk factors for the development of intrauterine adhesions following induced abortion. Additionally, intrauterine adhesions were observed in 105 mild, 80 moderate, and 70 severe cases. The cure rates for these three categories of intrauterine adhesions by hysteroscopic surgery were 100.0%, 93.8%, and 85.7%, respectively. Multiple pregnancies, high negative pressure suction evacuation and long suction evacuation time are independent risk factors for the development of intrauterine adhesions following induced abortions. Hysteroscopic surgery substantially improves the clinical outcomes of intrauterine adhesions.

Myeloid-cell protein tyrosine phosphatase-1B deficiency in mice protects against high-fat diet and lipopolysaccharide-induced inflammation, hyperinsulinemia, and endotoxemia through an IL-10 STAT3-dependent mechanism.

PubMed

Grant, Louise; Shearer, Kirsty D; Czopek, Alicja; Lees, Emma K; Owen, Carl; Agouni, Abdelali; Workman, James; Martin-Granados, Cristina; Forrester, John V; Wilson, Heather M; Mody, Nimesh; Delibegovic, Mirela

2014-02-01

Protein tyrosine phosphatase-1B (PTP1B) negatively regulates insulin and leptin signaling, rendering it an attractive drug target for treatment of obesity-induced insulin resistance. However, some studies suggest caution when targeting macrophage PTP1B, due to its potential anti-inflammatory role. We assessed the role of macrophage PTP1B in inflammation and whole-body metabolism using myeloid-cell (LysM) PTP1B knockout mice (LysM PTP1B). LysM PTP1B mice were protected against lipopolysaccharide (LPS)-induced endotoxemia and hepatic damage associated with decreased proinflammatory cytokine secretion in vivo. In vitro, LPS-treated LysM PTP1B bone marrow-derived macrophages (BMDMs) displayed increased interleukin (IL)-10 mRNA expression, with a concomitant decrease in TNF-α mRNA levels. These anti-inflammatory effects were associated with increased LPS- and IL-10-induced STAT3 phosphorylation in LysM PTP1B BMDMs. Chronic inflammation induced by high-fat (HF) feeding led to equally beneficial effects of macrophage PTP1B deficiency; LysM PTP1B mice exhibited improved glucose and insulin tolerance, protection against LPS-induced hyperinsulinemia, decreased macrophage infiltration into adipose tissue, and decreased liver damage. HF-fed LysM PTP1B mice had increased basal and LPS-induced IL-10 levels, associated with elevated STAT3 phosphorylation in splenic cells, IL-10 mRNA expression, and expansion of cells expressing myeloid markers. These increased IL-10 levels negatively correlated with circulating insulin and alanine transferase levels. Our studies implicate myeloid PTP1B in negative regulation of STAT3/IL-10-mediated signaling, highlighting its inhibition as a potential anti-inflammatory and antidiabetic target in obesity.

Conflict adaptation in positive and negative mood: Applying a success-failure manipulation.

PubMed

Schuch, Stefanie; Zweerings, Jana; Hirsch, Patricia; Koch, Iring

2017-05-01

Conflict adaptation is a cognitive mechanism denoting increased cognitive control upon detection of conflict. This mechanism can be measured by the congruency sequence effect, indicating the reduction of congruency effects after incongruent trials (where response conflict occurs) relative to congruent trials (without response conflict). Several studies have reported increased conflict adaptation under negative, as compared to positive, mood. In these studies, sustained mood states were induced by film clips or music combined with imagination techniques; these kinds of mood manipulations are highly obvious, possibly distorting the actual mood states experienced by the participants. Here, we report two experiments where mood states were induced in a less obvious way, and with higher ecological validity. Participants received success or failure feedback on their performance in a bogus intelligence test, and this mood manipulation proved highly effective. We largely replicated previous findings of larger conflict adaptation under negative mood than under positive mood, both with a Flanker interference paradigm (Experiment 1) and a Stroop-like interference paradigm (Experiment 2). Results are discussed with respect to current theories on affective influences on cognitive control. Copyright © 2017 Elsevier B.V. All rights reserved.

Defence response of tomato seedlings to oxidative stress induced by phenolic compounds from dry olive mill residue.

PubMed

García-Sánchez, Mercedes; Garrido, Inmaculada; Casimiro, Ilda de Jesús; Casero, Pedro Joaquín; Espinosa, Francisco; García-Romera, Inmaculada; Aranda, Elisabet

2012-10-01

ADOR is an aqueous extract obtained from the dry olive mill residue (DOR) which contains the majority of its soluble phenolic compounds, which are responsible for its phytotoxic properties. Some studies have shown that ADOR negatively affects seed germination. However, to date, few studies have been carried out on the effect of ADOR on the oxidative stress of the plant. It is well known that saprobe fungi can detoxify these phenolic compounds and reduce the potential negative effects of ADOR on plants. To gain a better understanding of the phytotoxic effects and oxidative stress caused by this residue, tomato seeds were germinated in the presence of ADOR, treated and untreated with Coriolopsis rigida, Trametes versicolor, Pycnoporus cinnabarinus and Penicillium chrysogenum-10 saprobe fungi. ADOR sharply reduced tomato seed germination and also generated high levels of malondialdehyde (MDA), O(2)(-) and H(2)O(2). However, bioremediated ADOR did not negatively affect germination and reduced MDA, O(2)(-) and H(2)O(2) content in different ways depending on the fungus used. In addition, the induced defense response was studied by analyzing the activity of both antioxidant enzymes (superoxide dismutase (SOD), catalase, ascorbate peroxidasa, glutathione reductase (GR), peroxidases and coniferil alcohol peroxidasa) and detoxification enzymes (glutathione-S-transferase (GST)). Our findings suggest that, because ADOR is capable of inducing oxidative stress, tomato seedlings trigger a defense response through SOD, GR, and GST activity and through antioxidant and lignification processes. On the other hand, the bioremediation of ADOR plays an important role in counteracting the oxidative stress induced by the untreated residue. Copyright © 2012 Elsevier Ltd. All rights reserved.

Negative Inotropic Effects of High Mobility Box Group 1 Protein in Isolated Contracting Cardiac Myocytes

PubMed Central

Tzeng, Huei-Ping; Fan, Jinping; Vallejo, Jesus G.; Dong, Jian Wen; Chen, Xiongwen; Houser, Steven R.; Mann, Douglas L.

2013-01-01

HMGB1 released from necrotic cells or macrophages functions as a late inflammatory mediator, and has been shown to induce cardiovascular collapse during sepsis. Thus far, however, the effect(s) of HMGB1 in the heart are not known. We determined the effects of HMGB1 on isolated feline cardiac myocytes by measuring sarcomere shortening in contracting cardiac myocytes, intracellular Ca2+ transients using fluo-3, and L-type calcium currents using whole cell perforate configuration of the patch clamp technique. Treatment of isolated myocytes with HMGB1 (100 ng/ml) resulted in a 70% decrease in sarcomere shortening and a 50% decrease in the height of the peak Ca++ transient within 5 min (p <0.01). The immediate negative inotropic effects HMGB1 on cell contractility and calcium homeostasis were partially reversible upon washout of HMGB1. A significant inhibition of the inward L-type calcium currents also was documented by the patch clamp technique. HMGB1 induced the PKCε translocation and a PKC inhibitor significantly attenuated the negative inotropic effects of HMGB1. These studies show for the first time that HMGB1 impairs sarcomere shortening by decreasing calcium availability in cardiac myocytes through modulating membrane calcium influx, and suggest that HMGB1 maybe act as a novel myocardial depressant factor during cardiac injury. PMID:18223193

Predator-induced phenotypic plasticity within- and across-generations: a challenge for theory?

PubMed Central

Walsh, Matthew R.; Cooley, Frank; Biles, Kelsey; Munch, Stephan B.

2015-01-01

Much work has shown that the environment can induce non-genetic changes in phenotype that span multiple generations. Theory predicts that predictable environmental variation selects for both increased within- and across-generation responses. Yet, to the best of our knowledge, there are no empirical tests of this prediction. We explored the relationship between within- versus across-generation plasticity by evaluating the influence of predator cues on the life-history traits of Daphnia ambigua. We measured the duration of predator-induced transgenerational effects, determined when transgenerational responses are induced, and quantified the cues that activate transgenerational plasticity. We show that predator exposure during embryonic development causes earlier maturation and increased reproductive output. Such effects are detectable two generations removed from predator exposure and are similar in magnitude in response to exposure to cues emitted by injured conspecifics. Moreover, all experimental contexts and traits yielded a negative correlation between within- versus across-generation responses. That is, responses to predator cues within- and across-generations were opposite in sign and magnitude. Although many models address transgenerational plasticity, none of them explain this apparent negative relationship between within- and across-generation plasticities. Our results highlight the need to refine the theory of transgenerational plasticity. PMID:25392477

Protective effect of ascorbic acid on netilmicin-induced lipid profile and peroxidation parameters in rabbit blood plasma.

PubMed

Devbhuti, Pritesh; Sikdar, Debasis; Saha, Achintya; Sengupta, Chandana

2011-01-01

A drug may cause alteration in blood-lipid profile and induce lipid peroxidation phenomena on administration in the body. Antioxidant may play beneficial role to control the negative alteration in lipid profile and lipid peroxidation. In view of this context, the present in vivo study was carried out to evaluate the role of ascorbic acid as antioxidant on netilmicin-induced alteration of blood lipid profile and peroxidation parameters. Rabbits were used as experimental animals and blood was collected to estimate blood-lipid profiles, such as total cholesterol (TCh), high density lipoprotein cholesterol (HDL-Ch), low density lipoprotein cholesterol (LDL-Ch), very low density lipoprotein cholesterol (VLDL-Ch), triglycerides (Tg), phospholipids (PL), and total lipids (TL), as well as peroxidation parameters, such as malondialdehyde (MDA), 4-hydroxy-2-nonenal (HNE), reduced glutathione (GSH) and nitric oxide (NO). The results revealed that netilmicin caused significant enhancement of MDA, HNE, TCh, LDL-Ch, VLDL-Ch, Tg levels and reduction in GSH, NO, HDL-Ch, PL, TL levels. On co-administration, ascorbic acid was found to be effective in reducing netilmicin-induced negative alterations of the above parameters.

Exercise prevents high fat diet-induced bone loss, marrow adiposity and dysbiosis in male mice.

PubMed

McCabe, Laura R; Irwin, Regina; Tekalur, Arjun; Evans, Christian; Schepper, Jonathan D; Parameswaran, Narayanan; Ciancio, Mae

2018-03-29

High fat diets can have detrimental effects on the skeleton as well as cause intestinal dysbiosis. Exercise prevents high fat (HF) diet-induced obesity and also improves bone density and prevents the intestinal dysbiosis that promotes energy storage. Previous studies indicate a link between intestinal microbial balance and bone health. Therefore, we examined whether exercise could prevent HF-induced bone pathology in male mice and determined whether benefits correlate to changes in host intestinal microbiota. Male C57Bl/6 mice were fed either a low fat diet (LF; 10 kcal% fat) or a HF diet (60 kcal% fat) and put under sedentary or voluntary exercise conditions for 14 weeks. Our results indicated that HF diet reduced trabecular bone volume, when corrected for differences in body weight, of both the tibia (40% reduction) and vertebrae (25% reduction) as well and increased marrow adiposity (44% increase). More importantly, these effects were prevented by exercise. Exercise also had a significant effect on several cortical bone parameters and enhanced bone mechanical properties in LF but not HF fed mice. Microbiome analyses indicated that exercise altered the HF induced changes in microbial composition by reducing the Firmicutes/Bacteriodetes ratio. This ratio negatively correlated with bone volume as did levels of Clostridia and Lachnospiraceae. In contrast, the abundance of several Actinobacteria phylum members (i.e., Bifidobacteriaceae) were positively correlated with bone volume. Taken together, exercise can prevent many of the negative effects of a high fat diet on male skeletal health. Exercise induced changes in microbiota composition could represent a novel mechanism that contributes to exercise induced benefits to bone health. Copyright © 2018 Elsevier Inc. All rights reserved.

Kinetochore identification in micronuclei in mouse bone-marrow erythrocytes: an assay for the detection of aneuploidy-inducing agents.

PubMed

Gudi, R; Sandhu, S S; Athwal, R S

1990-10-01

An in vivo micronucleus assay using mouse bone marrow for identifying the ability of chemicals to induce aneuploidy and/or chromosome breaks is described. Micronucleus formation in bone-marrow erythrocytes of mice is commonly used as an index for evaluating the clastogenicity of environmental agents. However, micronuclei may also originate from intact lagging chromosomes resulting from the effect of aneuploidy-inducing agents. We have used immunofluorescent staining using anti-kinetochore antibodies to classify micronuclei for the presence or absence of kinetochores. Micronuclei positive for kinetochores are assumed to contain intact chromosomes and result from induced aneuploidy; while those negative for kinetochores contain acentric chromosomal fragments and originate from clastogenic events. The assay was evaluated using X-irradiation (a known clastogen) and vincristine sulfate (an aneuploidy-inducing agent). A dose-related response for the induction of micronuclei was observed for both agents. Micronuclei induced by X-irradiation were negative for kinetochores while the majority of the micronuclei resulting from vincristine treatment contained kinetochores. Thus, the micronucleus assay in combination with immunofluorescent staining for kinetochores may provide a useful method to simultaneously assess the ability of chemicals to induce aneuploidy and/or chromosome breaks.

Involvement of Phosphatidylinositol 3-Kinase-Mediated Up-Regulation of IκBα in Anti-Inflammatory Effect of Gemfibrozil in Microglia1

PubMed Central

Jana, Malabendu; Jana, Arundhati; Liu, Xiaojuan; Ghosh, Sankar; Pahan, Kalipada

2008-01-01

The present study underlines the importance of PI3K in mediating the anti-inflammatory effect of gemfibrozil, a prescribed lipid-lowering drug for humans, in mouse microglia. Gemfibrozil inhibited LPS-induced expression of inducible NO synthase (iNOS) and proinflammatory cytokines in mouse BV-2 microglial cells and primary microglia. By overexpressing wild-type and dominant-negative constructs of peroxisome proliferator-activated receptor-α (PPAR-α) in microglial cells and isolating primary microglia from PPAR-α−/− mice, we have demonstrated that gemfibrozil inhibits the activation of microglia independent of PPAR-α. Interestingly, gemfibrozil induced the activation of p85α-associated PI3K (p110β but not p110α) and inhibition of that PI3K by either chemical inhibitors or dominant-negative mutants abrogated the inhibitory effect of gemfibrozil. Conversely, overexpression of the constitutively active mutant of p110 enhanced the inhibitory effect of gemfibrozil on LPS-induced expression of proinflammatory molecules. Similarly, gemfibrozil also inhibited fibrillar amyloid β (Aβ)-, prion peptide (PrP)-, dsRNA (poly IC)-, HIV-1 Tat-, and 1-methyl-4-phenylpyridinium (MPP+)-, but not IFN-γ-, induced microglial expression of iNOS. Inhibition of PI3K also abolished the inhibitory effect of gemfibrozil on Aβ-, PrP-, poly IC-, Tat-, and MPP+-induced microglial expression of iNOS. Involvement of NF-κB activation in LPS-, Aβ-, PrP-, poly IC-, Tat-, and MPP+-, but not IFN-γ-, induced microglial expression of iNOS and stimulation of IκBα expression and inhibition of NF-κB activation by gemfibrozil via the PI3K pathway suggests that gemfibrozil inhibits the activation of NF-κB and the expression of proinflammatory molecules in microglia via PI3K-mediated up-regulation of IκBα. PMID:17785853

Tissue engineering bioreactor systems for applying physical and electrical stimulations to cells.

PubMed

Jin, GyuHyun; Yang, Gi-Hoon; Kim, GeunHyung

2015-05-01

Bioreactor systems in tissue engineering applications provide various types of stimulation to mimic the tissues in vitro and in vivo. Various bioreactors have been designed to induce high cellular activities, including initial cell attachment, cell growth, and differentiation. Although cell-stimulation processes exert mostly positive effects on cellular responses, in some cases such stimulation can also have a negative effect on cultured cells. In this review, we discuss various types of bioreactor and the positive and negative effects of stimulation (physical, chemical, and electrical) on various cultured cell types. © 2014 Wiley Periodicals, Inc.

Is it beneficial to use Internet-communication for escaping from boredom? Boredom proneness interacts with cue-induced craving and avoidance expectancies in explaining symptoms of Internet-communication disorder

PubMed Central

Ostendorf, Sina

2018-01-01

The use of online-communication applications including messengers (e.g. WhatsApp) or social networking services (e.g. Facebook) on the smartphone has turned into daily practice for billions of people, for example during waiting times. An increasing number of individuals show diminished control over their usage of these applications despite negative consequences in everyday life. This can be referred to as Internet-communication disorder (ICD). The current study investigated the effect of boredom proneness on symptoms of an ICD. It further examined the mediating role of cognitive and affective mechanisms, namely expectancies to avoid negative feelings online and cue-induced craving. The results of a structural equation model (N = 148) illustrate that boredom proneness is a risk factor for the development and maintenance of an ICD as it had a significant direct effect on ICD symptoms. Furthermore, boredom proneness predicted avoidance expectancies as well as cue-induced craving. Both in turn enhanced the risk of developing ICD tendencies. Moreover, both variables mediated the effect of boredom proneness on ICD and interacted among each other. In summary, the results demonstrate that people who have a higher susceptibility to experience boredom show higher expectancies to avoid negative emotions online, which promotes higher craving reactions when being confronted with specific cues (e.g. an incoming message), and could result in ICD tendencies. PMID:29672574

Is it beneficial to use Internet-communication for escaping from boredom? Boredom proneness interacts with cue-induced craving and avoidance expectancies in explaining symptoms of Internet-communication disorder.

PubMed

Wegmann, Elisa; Ostendorf, Sina; Brand, Matthias

2018-01-01

The use of online-communication applications including messengers (e.g. WhatsApp) or social networking services (e.g. Facebook) on the smartphone has turned into daily practice for billions of people, for example during waiting times. An increasing number of individuals show diminished control over their usage of these applications despite negative consequences in everyday life. This can be referred to as Internet-communication disorder (ICD). The current study investigated the effect of boredom proneness on symptoms of an ICD. It further examined the mediating role of cognitive and affective mechanisms, namely expectancies to avoid negative feelings online and cue-induced craving. The results of a structural equation model (N = 148) illustrate that boredom proneness is a risk factor for the development and maintenance of an ICD as it had a significant direct effect on ICD symptoms. Furthermore, boredom proneness predicted avoidance expectancies as well as cue-induced craving. Both in turn enhanced the risk of developing ICD tendencies. Moreover, both variables mediated the effect of boredom proneness on ICD and interacted among each other. In summary, the results demonstrate that people who have a higher susceptibility to experience boredom show higher expectancies to avoid negative emotions online, which promotes higher craving reactions when being confronted with specific cues (e.g. an incoming message), and could result in ICD tendencies.

The antecedents and belief-polarized effects of thought confidence.

PubMed

Chou, Hsuan-Yi; Lien, Nai-Hwa; Liang, Kuan-Yu

2011-01-01

This article investigates 2 possible antecedents of thought confidence and explores the effects of confidence induced before or during ad exposure. The results of the experiments indicate that both consumers' dispositional optimism and spokesperson attractiveness have significant effects on consumers' confidence in thoughts that are generated after viewing the advertisement. Higher levels of thought confidence will influence the quality of the thoughts that people generate, lead to either positively or negatively polarized message processing, and therefore induce better or worse advertising effectiveness, depending on the valence of thoughts. The authors posit the belief-polarization hypothesis to explain these findings.

High-frequency rTMS on DLPFC increases prosocial attitude in case of decision to support people.

PubMed

Balconi, Michela; Canavesio, Ylenia

2014-02-01

Engaging in prosocial behavior was explored in the present research, by investigating the role of dorsolateral prefrontal cortex (DLPFC) in modulation of intention to support other people and of emotional attuning as it was expressed by facial feedback (electromiography, EMG). High-frequency rTMS was applied on DLPFC to 25 subjects when they were required to choose to directly intervene or not to support other people in emotionally valenced social situations (cooperative, noncooperative, conflictual, neutral contexts). Two control conditions were included in the experimental design to control the simple stimulation effect (sham condition with absence of TMS stimulation) and the location effect (control site condition with Pz stimulation). In comparison with sham and control condition, rTMS stimulation induced increased prosocial behavior in all the emotional situations. Moreover, as a function of valence, zygomatic (for positive situations) and corrugators (for negative situations) muscle activity was increased, with significant effect by DLPFC stimulation which induced a "facilitation effect". In addition, negative situations showed a higher rTMS impact for both behavioral and EMG responsiveness. Finally, prosocial behavior was found to be predicted (regression analysis) by EMG variations, as a function of the negative versus positive valence. The prefrontal circuit was suggested to support emotional responsiveness and facial feedback in order to facilitate the prosocial behavior.

Did I Do That? Expectancy Effects of Brain Stimulation on Error-related Negativity and Sense of Agency.

PubMed

Hoogeveen, Suzanne; Schjoedt, Uffe; van Elk, Michiel

2018-06-19

This study examines the effects of expected transcranial stimulation on the error(-related) negativity (Ne or ERN) and the sense of agency in participants who perform a cognitive control task. Placebo transcranial direct current stimulation was used to elicit expectations of transcranially induced cognitive improvement or impairment. The improvement/impairment manipulation affected both the Ne/ERN and the sense of agency (i.e., whether participants attributed errors to oneself or the brain stimulation device): Expected improvement increased the ERN in response to errors compared with both impairment and control conditions. Expected impairment made participants falsely attribute errors to the transcranial stimulation. This decrease in sense of agency was correlated with a reduced ERN amplitude. These results show that expectations about transcranial stimulation impact users' neural response to self-generated errors and the attribution of responsibility-especially when actions lead to negative outcomes. We discuss our findings in relation to predictive processing theory according to which the effect of prior expectations on the ERN reflects the brain's attempt to generate predictive models of incoming information. By demonstrating that induced expectations about transcranial stimulation can have effects at a neural level, that is, beyond mere demand characteristics, our findings highlight the potential for placebo brain stimulation as a promising tool for research.

Cooperative effect of random and time-periodic coupling strength on synchronization transitions in one-way coupled neural system: mean field approach.

PubMed

Jiancheng, Shi; Min, Luo; Chusheng, Huang

2017-08-01

The cooperative effect of random coupling strength and time-periodic coupling strengh on synchronization transitions in one-way coupled neural system has been investigated by mean field approach. Results show that cooperative coupling strength (CCS) plays an active role for the enhancement of synchronization transitions. There exist an optimal frequency of CCS which makes the system display the best CCS-induced synchronization transitions, a critical frequency of CCS which can not further affect the CCS-induced synchronization transitions, and a critical amplitude of CCS which can not occur the CCS-induced synchronization transitions. Meanwhile, noise intensity plays a negative role for the CCS-induced synchronization transitions. Furthermore, it is found that the novel CCS amplitude-induced synchronization transitions and CCS frequency-induced synchronization transitions are found.

Attention during adaptation weakens negative afterimages of perceptually colour-spread surfaces.

PubMed

Lak, Armin

2008-06-01

The visual system can complete coloured surfaces from stimulus fragments, inducing the subjective perception of a colour-spread figure. Negative afterimages of these induced colours were first reported by S. Shimojo, Y. Kamitani, and S. Nishida (2001). Two experiments were conducted to examine the effect of attention on the duration of these afterimages. The results showed that shifting attention to the colour-spread figure during the adaptation phase weakened the subsequent afterimage. On the basis of previous findings that the duration of these afterimages is correlated with the strength of perceptual filling-in (grouping) among local inducers during the adaptation phase, it is proposed that attention weakens perceptual filling-in during the adaptation phase and thereby prevents the stimulus from being segmented into an illusory figure. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

More physicians: improved availability or induced demand?

PubMed

Carlsen, F; Grytten, J

1998-09-01

A number of empirical studies have shown that there is a negative association between population:physician ratio and utilization of medical services. However, it is not clear whether this relationship reflects supplier-inducement, the effect of lower prices on patient demand, a supply response to variation in health status, or improved availability. In Norway, patient fees and state reimbursement fees are set centrally. Therefore, the correlation between utilization and population:physician ratio either reflects supplier-inducement, a supply response or an availability effect. We applied a theoretical model which distinguished between an inducement and an availability effect. The model was implemented on a cross-sectional data set which contained information about patient visits and laboratory tests for all fee-for-service primary care physicians in Norway. Since population:physician ratio is potentially endogenous, an instrumental variable approach is used. We found no evidence for inducement either for number of visits or for provision of laboratory services.

Selective cytoprotective effect of histamine on doxorubicin-induced hepatic and cardiac toxicity in animal models

PubMed Central

Lamas, DJMartinel; Nicoud, MB; Sterle, HA; Carabajal, E; Tesan, F; Perazzo, JC; Cremaschi, GA; Rivera, ES; Medina, VA

2015-01-01

The aim of the present work was to evaluate the potential protective effect of histamine on Doxorubicin (Dox)-induced hepatic and cardiac toxicity in different rodent species and in a triple-negative breast tumor-bearing mice model. Male Sprague Dawley rats and Balb/c mice were divided into four groups: control (received saline), histamine (5 mg/kg for rats and 1 mg/kg for mice, daily subcutaneous injection starting 24 h before treatment with Dox), Dox (2 mg/kg, intraperitoneally injected three times a week for 2 weeks) and Dox+histamine (received both treatments). Tissue toxicity was evaluated by histopathological studies and oxidative stress and biochemical parameters. The combined effect of histamine and Dox was also investigated in vitro and in vivo in human MDA-MB-231 triple-negative breast cancer model. Heart and liver of Dox-treated animals displayed severe histological damage, loss of tissue weight, increased TBARS levels and DNA damage along with an augment in serum creatine kinase-myocardial band. Pretreatment with histamine prevented Dox-induced tissue events producing a significant preservation of the integrity of both rat and mouse myocardium and liver, through the reduction of Dox-induced oxidative stress and apoptosis. Histamine treatment preserved anti-tumor activity of Dox, exhibiting differential cytotoxicity and increasing the Dox-induced inhibition of breast tumor growth. Findings provide preclinical evidence indicating that histamine could be a promising candidate as a selective cytoprotective agent for the treatment of Dox-induced cardiac and hepatic toxicity, and encourage the translation to clinical practice. PMID:27551485

Inhibition of alpha interferon (IFN-α)-induced microRNA-122 negatively affects the anti-hepatitis B virus efficiency of IFN-α.

PubMed

Hao, Junli; Jin, Wensong; Li, Xinghui; Wang, Saifeng; Zhang, Xiaojun; Fan, Hongxia; Li, Changfei; Chen, Lizhao; Gao, Bin; Liu, Guangze; Meng, Songdong

2013-01-01

Alpha interferon (IFN-α)-based therapy can effectively treat chronic hepatitis B virus (HBV) infection, which causes life-threatening complications. Responses to IFN-α therapy vary greatly in chronic hepatitis B (CHB) patients, but underlying mechanisms are almost unknown. In this study, we found that IFN-α treatment induced a marked decrease of microRNA-122 (miR-122) expression in hepatocytes. We next showed that IFN-α-induced miR-122 downregulation was only partly due to transcriptional suppression. One IFN-stimulated gene (ISG), NT5C3, which was identified as a miR-122 target, efficiently inhibited miR-122 by binding and sequestering miR-122 with its mRNA 3'-untranslated region (3'-UTR), indicating that this ISG is involved in IFN-α-mediated miR-122 suppression. Notably, the inhibitory effect of IFN-α on miR-122 was completely abolished by blocking IFN-α-induced upregulation of NT5C3 mRNA expression by RNA interference (RNAi). Meanwhile, we observed that miR-122 dramatically inhibited HBV expression and replication. Finally, we showed that IFN-α-mediated HBV-inhibitory effects could be enhanced significantly by blocking IFN-α-induced downregulation of miR-122. We therefore concluded that IFN-α-induced inhibition of miR-122 may negatively affect the anti-HBV function of IFN-α. These data provide valuable insights for a better understanding of the antiviral mechanism of IFN-α and raise further potential interest in enhancing its anti-HBV efficacy.

Inhibition of Alpha Interferon (IFN-α)-Induced MicroRNA-122 Negatively Affects the Anti-Hepatitis B Virus Efficiency of IFN-α

PubMed Central

Hao, Junli; Jin, Wensong; Li, Xinghui; Wang, Saifeng; Zhang, Xiaojun; Fan, Hongxia; Li, Changfei; Chen, Lizhao; Gao, Bin

2013-01-01

Alpha interferon (IFN-α)-based therapy can effectively treat chronic hepatitis B virus (HBV) infection, which causes life-threatening complications. Responses to IFN-α therapy vary greatly in chronic hepatitis B (CHB) patients, but underlying mechanisms are almost unknown. In this study, we found that IFN-α treatment induced a marked decrease of microRNA-122 (miR-122) expression in hepatocytes. We next showed that IFN-α-induced miR-122 downregulation was only partly due to transcriptional suppression. One IFN-stimulated gene (ISG), NT5C3, which was identified as a miR-122 target, efficiently inhibited miR-122 by binding and sequestering miR-122 with its mRNA 3′-untranslated region (3′-UTR), indicating that this ISG is involved in IFN-α-mediated miR-122 suppression. Notably, the inhibitory effect of IFN-α on miR-122 was completely abolished by blocking IFN-α-induced upregulation of NT5C3 mRNA expression by RNA interference (RNAi). Meanwhile, we observed that miR-122 dramatically inhibited HBV expression and replication. Finally, we showed that IFN-α-mediated HBV-inhibitory effects could be enhanced significantly by blocking IFN-α-induced downregulation of miR-122. We therefore concluded that IFN-α-induced inhibition of miR-122 may negatively affect the anti-HBV function of IFN-α. These data provide valuable insights for a better understanding of the antiviral mechanism of IFN-α and raise further potential interest in enhancing its anti-HBV efficacy. PMID:23055569

Conflict-driven adaptive control is enhanced by integral negative emotion on a short time scale.

PubMed

Yang, Qian; Pourtois, Gilles

2018-02-05

Negative emotion influences cognitive control, and more specifically conflict adaptation. However, discrepant results have often been reported in the literature. In this study, we broke down negative emotion into integral and incidental components using a modern motivation-based framework, and assessed whether the former could change conflict adaptation. In the first experiment, we manipulated the duration of the inter-trial-interval (ITI) to assess the actual time-scale of this effect. Integral negative emotion was induced by using loss-related feedback contingent on task performance, and measured at the subjective and physiological levels. Results showed that conflict-driven adaptive control was enhanced when integral negative emotion was elicited, compared to a control condition without changes in defensive motivation. Importantly, this effect was only found when a short, as opposed to long ITI was used, suggesting that it had a short time scale. In the second experiment, we controlled for effects of feature repetition and contingency learning, and replicated an enhanced conflict adaptation effect when integral negative emotion was elicited and a short ITI was used. We interpret these new results against a standard cognitive control framework assuming that integral negative emotion amplifies specific control signals transiently, and in turn enhances conflict adaptation.

Radiosensitivity and effect of hypoxia in HPV positive head and neck cancer cells.

PubMed

Sørensen, Brita Singers; Busk, Morten; Olthof, Nadine; Speel, Ernst-Jan; Horsman, Michael R; Alsner, Jan; Overgaard, Jens

2013-09-01

HPV associated Head and Neck Squamous Cell Carcinoma (HNSCC) represents a distinct subgroup of HNSCC characterized by a favorable prognosis and a distinct molecular biology. Previous data from the randomized DAHANCA 5 trial indicated that HPV positive tumors did not benefit from hypoxic modifications by Nimorazole during radiotherapy, whereas a significant benefit was observed in the HPV negative tumors. However, more studies have demonstrated equal frequencies of hypoxic tumors among HPV-positive and HPV-negative tumors. The aim of the present study was to determine radiosensitivity, the impact of hypoxia and the effect of Nimorazole in HPV positive and HPV negative cell lines. The used cell lines were: UDSCC2, UMSCC47 and UPCISCC90 (HPV positive) and FaDuDD, UTSCC33 and UTSCC5 (HPV negative). Cells were cultured under normoxic or hypoxic conditions, and gene expression levels of previously established hypoxia induced genes were assessed by qPCR. Cells were irradiated with various doses under normoxia, hypoxia or hypoxia +1mM Nimorazole, and the clonogenic survival was determined. The HPV positive and HPV negative cell lines exhibited similar patterns of upregulation of hypoxia induced genes in response to hypoxia. The HPV positive cell lines were up to 2.4 times more radiation sensitive than HPV negative cell lines. However, all HPV positive cells displayed the same response to hypoxia in radiosensitivity, with an OER in the range 2.3-2.9, and a sensitizer effect of Nimorazole of 1.13-1.29, similar to HPV negative cells. Although HPV positive cells had a markedly higher radiosensitivity compared to HPV negative cells, they displayed the same relative radioresistance under hypoxia and the same relative sensitizer effect of Nimorazole. The clinical observation that HPV positive patients do not seem to benefit from Nimorazole treatment is not due to inherent differences in hypoxia sensitivity or response to Nimorazole, but can be accounted for by the overall higher radiosensitivity of HPV positive cells. Copyright © 2013. Published by Elsevier Ireland Ltd.

Maslinic acid ameliorates NMDA receptor blockade-induced schizophrenia-like behaviors in mice.

PubMed

Jeon, Se Jin; Kim, Eunji; Lee, Jin Su; Oh, Hee Kyong; Zhang, Jiabao; Kwon, Yubeen; Jang, Dae Sik; Ryu, Jong Hoon

2017-11-01

Schizophrenia is a chronic psychotic disorder characterized by positive, negative, and cognitive symptoms. Primary treatments for schizophrenia relieve the positive symptoms but are less effective against the negative and cognitive symptoms. In the present study, we investigated whether maslinic acid, isolated from Syzygium aromaticum (clove), can ameliorate schizophrenia-like behaviors in mice induced by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. After maslinic acid treatment in the MK-801 model, we examined the behavioral alteration and signaling pathways in the prefrontal cortex. Mice were treated with maslinic acid (30 mg/kg), and their behaviors were evaluated through an array of behavioral tests. The effects of maslinic acid were also examined in the signaling pathways in the prefrontal cortex. A single administration of maslinic acid blocked the MK-801-induced hyperlocomotion and reversed the MK-801-induced sensorimotor gating deficit in the acoustic startle response test. In the social novelty preference test, maslinic acid ameliorated the social behavior deficits induced by MK-801. The MK-801-induced attention and recognition memory impairments were also alleviated by a single administration of maslinic acid. Furthermore, maslinic acid normalized the phosphorylation levels of Akt-GSK-3β and ERK-CREB in the prefrontal cortex. Overall, maslinic acid ameliorated the schizophrenia-like symptoms induced by MK-801, and these effects may be partly mediated through Akt-GSK-3β and ERK-CREB activation. These findings suggest that maslinic acid could be a candidate for the treatment of several symptoms of schizophrenia, including positive symptoms, sensorimotor gating disruption, social interaction deficits, and cognitive impairments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heat shock protein 70 negatively regulates the heat-shock-induced suppression of the I{kappa}B/NF-{kappa}B cascade by facilitating I{kappa}B kinase renaturation and blocking its further denaturation

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

Lee, Kyoung-Hee; Lee, Choon-Taek; Kim, Young Whan

2005-07-01

Heat shock (HS) treatment has been previously shown to suppress the I{kappa}B/nuclear factor-{kappa}B (NF-{kappa}B) cascade by denaturing, and thus inactivating I{kappa}B kinase (IKK). HS is characterized by the induction of a group of heat shock proteins (HSPs). However, their role in the HS-induced suppression of the I{kappa}B/NF-{kappa}B cascade is unclear. Adenovirus-mediated HSP70 overexpression was found not to suppress the TNF-{alpha}-induced activation of the I{kappa}B/NF-{kappa}B pathway, thus suggesting that HSP70 is unlikely to suppress this pathway. When TNF-{alpha}-induced activation of the I{kappa}B/NF-{kappa}B pathway was regained 24 h after HS, HSP70 was found to be highly up-regulated. Moreover, blocking HSP70 induction delayedmore » TNF-{alpha}-induced I{kappa}B{alpha} degradation and the resolubilization of IKK. In addition, HSP70 associated physically with IKK, suggesting that HSP70 is involved in the recovery process via molecular chaperone effect. Adenovirus-mediated HSP70 overexpression prior to HS blocked the I{kappa}B{alpha} stabilizing effect of HS by suppressing IKK insolubilization. Moreover, the up-regulation of endogenous HSP70 by preheating, suppressed this subsequent HS-induced IKK insolubilization, and this effect was abrogated by blocking HSP70 induction. These findings indicate that HSP70 accumulates during HS and negatively regulates the HS-induced suppression of the I{kappa}B/NF-{kappa}B cascade by facilitating the renaturation of IKK and blocking its further denaturation.« less

Negative Urgency Is Associated With Heightened Negative Affect and Urge During Tobacco Abstinence in Regular Smokers

PubMed Central

Park, Annie D.; Farrahi, Layla N.; Pang, Raina D.; Guillot, Casey R.; Aguirre, Claudia G.; Leventhal, Adam M.

2016-01-01

Objective: Negative urgency—the tendency to act rashly during negative affective states—is a risk factor for regular cigarette smoking. This human laboratory study tested a novel theoretical model of the underlying mechanisms linking negative urgency and smoking motivation, which purports that smokers with high negative urgency are at increased susceptibility to abstinence-induced increases in negative affect, which, in turn, provokes the urge to smoke to suppress negative affect. Method: Smokers (N = 180, >10 cigarettes/day) attended a baseline session at which they completed self-report measures of negative urgency and other co-factors and subsequently attended two counterbalanced within-subject experimental sessions (i.e., 16 hours of smoking abstinence or smoking as usual). At both experimental sessions, self-reported tobacco withdrawal symptoms, affect, and smoking urge were assessed. Results: Negative urgency was associated with larger abstinence-induced increases in tobacco withdrawal symptoms, negative affect, and urge to smoke to alleviate negative affect, both with and without controlling for anxiety, depression, tobacco dependence, and sensation seeking (βs > .18, ps < .05). The association between negative urgency and abstinence-induced increases in urge to smoke to alleviate negative affect was mediated by greater abstinence-induced increases in negative affect (βs > .062, ps = .01). Conclusions: These results provide initial support of this model by providing evidence that smokers with higher (vs. lower) negative urgency may be more prone to greater negative affect during withdrawal, which in turn may promote urge to smoke to suppress negative emotion. Research extending this model to other settings, measures, and methodological approaches may be fruitful. PMID:27588535

Negative Urgency Is Associated With Heightened Negative Affect and Urge During Tobacco Abstinence in Regular Smokers.

PubMed

Park, Annie D; Farrahi, Layla N; Pang, Raina D; Guillot, Casey R; Aguirre, Claudia G; Leventhal, Adam M

2016-09-01

Negative urgency-the tendency to act rashly during negative affective states-is a risk factor for regular cigarette smoking. This human laboratory study tested a novel theoretical model of the underlying mechanisms linking negative urgency and smoking motivation, which purports that smokers with high negative urgency are at increased susceptibility to abstinence-induced increases in negative affect, which, in turn, provokes the urge to smoke to suppress negative affect. Smokers (N = 180, >10 cigarettes/day) attended a baseline session at which they completed self-report measures of negative urgency and other co-factors and subsequently attended two counterbalanced within-subject experimental sessions (i.e., 16 hours of smoking abstinence or smoking as usual). At both experimental sessions, self-reported tobacco withdrawal symptoms, affect, and smoking urge were assessed. Negative urgency was associated with larger abstinence-induced increases in tobacco withdrawal symptoms, negative affect, and urge to smoke to alleviate negative affect, both with and without controlling for anxiety, depression, tobacco dependence, and sensation seeking (βs > .18, ps < .05). The association between negative urgency and abstinence-induced increases in urge to smoke to alleviate negative affect was mediated by greater abstinence-induced increases in negative affect (βs > .062, ps = .01). These results provide initial support of this model by providing evidence that smokers with higher (vs. lower) negative urgency may be more prone to greater negative affect during withdrawal, which in turn may promote urge to smoke to suppress negative emotion. Research extending this model to other settings, measures, and methodological approaches may be fruitful.

Laxatives Do Not Improve Symptoms of Opioid-Induced Constipation: Results of a Patient Survey

PubMed Central

Emmanuel, Anton; Johnson, Martin; McSkimming, Paula; Dickerson, Sara

2017-01-01

Abstract Introduction Laxatives are commonly used to treat opioid-induced constipation, the commonest and most bothersome complication of opioids. However, laxatives have a nonspecific action and do not target underlying mechanisms of opioid-induced constipation; their use is associated with abdominal symptoms that negatively impact quality of life. Objective To assess the effects of laxatives in patients taking opioids for chronic pain. Methods One hundred ninety-eight UK patients who had taken opioid analgesics for at least one month completed a cross-sectional online or telephone survey. Questions addressed their pain condition, medication, and laxative use (including efficacy and side effects). The survey also assessed bowel function using the Bowel Function Index. Results Since starting their current opioid, 134 of 184 patients (73%) had used laxatives at some point and 122 (91%) of these were currently taking them. The most common laxatives were osmotics and stimulants. Laxative side effects were reported in 75%, most commonly gas, bloating/fullness, and a sudden urge to defecate. Side effects were more common in patients less than 40 years of age. Approximately half of patients said laxatives interfered with work and social activities, and one-fifth needed an overnight hospital stay because of their pain condition and/or constipation. Laxatives did not improve the symptoms of constipation, as assessed by the Bowel Function Index. Constipation was not related to opioid strength, dose of opioid, or number of laxatives taken. Conclusions Use of laxatives to treat opioid-induced constipation is often ineffective and associated with side effects. Instead of relieving the burden of opioid-induced constipation, laxative use is associated with a negative impact. PMID:28339544

The Lévy noise-induced current reversal phenomenon for self-propelled particles in a two-dimensional potential

NASA Astrophysics Data System (ADS)

Wang, Bing; Qu, Zhongwei; Li, Xuechao; Ma, Jianli

2017-08-01

Effects of Lévy noise on self-propelled particles in a two-dimensional potential is investigated. The current reversal phenomenon appears in the system. V (x-direction average velocity) changes from negative to positive with increasing asymmetry parameter β, and changes from positive to negative with increasing self-propelled velocity v0. V has a maximum with increasing modulation constant λ.

Blocking negative effects of senescence in human skin fibroblasts with a plant extract.

PubMed

Lämmermann, Ingo; Terlecki-Zaniewicz, Lucia; Weinmüllner, Regina; Schosserer, Markus; Dellago, Hanna; de Matos Branco, André Dargen; Autheried, Dominik; Sevcnikar, Benjamin; Kleissl, Lisa; Berlin, Irina; Morizot, Frédérique; Lejeune, Francois; Fuzzati, Nicola; Forestier, Sandra; Toribio, Alix; Tromeur, Anaïs; Weinberg, Lionel; Higareda Almaraz, Juan Carlos; Scheideler, Marcel; Rietveld, Marion; El Ghalbzouri, Abdoel; Tschachler, Erwin; Gruber, Florian; Grillari, Johannes

2018-01-01

There is increasing evidence that senescent cells are a driving force behind many age-related pathologies and that their selective elimination increases the life- and healthspan of mice. Senescent cells negatively affect their surrounding tissue by losing their cell specific functionality and by secreting a pro-tumorigenic and pro-inflammatory mixture of growth hormones, chemokines, cytokines and proteases, termed the senescence-associated secretory phenotype (SASP). Here we identified an extract from the plant Solidago virgaurea subsp. alpestris , which exhibited weak senolytic activity, delayed the acquisition of a senescent phenotype and induced a papillary phenotype with improved functionality in human dermal fibroblasts. When administered to stress-induced premature senescent fibroblasts, this extract changed their global mRNA expression profile and particularly reduced the expression of various SASP components, thereby ameliorating the negative influence on nearby cells. Thus, the investigated plant extract represents a promising possibility to block age-related loss of tissue functionality.

[Identification and evaluation of the neuroleptic activity of phenotropil].

PubMed

Akhapkina, V I; Akhapkin, R V

2013-01-01

The neuroleptic (antipsychotic) activity of phenotropil was studied in an experimental animal model. Phenotropil had a marked neuroleptic activity in models of positive (apomorphine-induced verticalization test) and negative (5-HTP-induced hyperkinesis test) symptoms of psychoses as well as in the m-cholinergic pathway hyperactivation (arecoline-induced tremor test). The compound markedly antagonized haloperidol catalepsy. Used in a single dose or as a course treatment, phenotropil did not provoke aggression nor intensify it. In contrast to typical and atypical antipsychotics, phenotropil had no sedative action and other adverse effects. It exhibited a positive effect on exploratory behavior and motor activity, had anxiolytic and antidepressant action.

Relative Effectiveness of Reappraisal and Distraction in Regulating Emotion in Late-Life Depression

PubMed Central

Smoski, Moria J.; LaBar, Kevin S.; Steffens, David C.

2013-01-01

Objectives The present study compares the effectiveness of two strategies, reappraisal and distraction, in reducing negative affect in older adults induced by focusing on personally relevant negative events and stressors. Participants included 30 adults with MDD and 40 never-depressed (ND) comparison participants ages 60 and over (mean age = 69.7 years). Design and Measurements Participants underwent three affect induction trials, each followed by a different emotion regulation strategy: distraction, reappraisal, and a no-instruction control condition. Self-reported affect was recorded pre- and post-affect induction, and at one-minute intervals during regulation. Results Across groups, participants reported greater reductions in negative affect with distraction than reappraisal or the no-instruction control condition. An interaction between group and regulation condition indicated that distraction was more effective in reducing negative affect in the MDD group than the ND group. Conclusions These results suggest that distraction is an especially effective strategy for reducing negative affect in older adults with MDD. Finding ways to incorporate distraction skills into psychotherapeutic interventions for late-life MDD may improve their effectiveness, especially for short-term improvement of affect following rumination. PMID:24021222

Copper Contamination Impairs Herbivore Initiation of Seaweed Inducible Defenses and Decreases Their Effectiveness

PubMed Central

2015-01-01

Seaweed-herbivore interactions are often mediated by environmental conditions, yet the roles of emerging anthropogenic stressors on these interactions are poorly understood. For example, chemical contaminants have unknown consequences on seaweed inducible resistance and herbivore response to these defenses despite known deleterious effects of contaminants on animal inducible defenses. Here, we investigated the effect of copper contamination on the interactions between a snail herbivore and a brown seaweed that displays inducible resistance to grazing. We examined seaweed inducible resistance and its effectiveness for organisms exposed to copper at two time points, either during induction or after herbivores had already induced seaweed defenses. Under ambient conditions, non-grazed tissues were more palatable than grazed tissues. However, copper additions negated the preference for non-grazed tissues regardless of the timing of copper exposure, suggesting that copper decreased both how herbivores initiated these inducible defenses and their subsequent effectiveness. Copper decreased stimulation of defenses, at least in part, by suppressing snail grazing pressure—the cue that turns inducible defenses on. Copper decreased effectiveness of defenses by preventing snails from preferentially consuming non-grazed seaweed. Thus, contaminants can potentially stress communities by changing seaweed-herbivore interactions mediated via inducible defenses. Given the ubiquity of seaweed inducible resistance and their potential influence on herbivores, we hypothesize that copper contamination may change the impact of these resistant traits on herbivores. PMID:26274491

Repression of osteoblast maturation by ERRα accounts for bone loss induced by estrogen deficiency.

PubMed

Gallet, Marlène; Saïdi, Soraya; Haÿ, Eric; Photsavang, Johann; Marty, Caroline; Sailland, Juliette; Carnesecchi, Julie; Tribollet, Violaine; Barenton, Bruno; Forcet, Christelle; Birling, Marie-Christine; Sorg, Tania; Chassande, Olivier; Cohen-Solal, Martine; Vanacker, Jean-Marc

2013-01-01

ERRα is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRα negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRα on osteoblast maturation are responsible for one or both types of in vivo induced bone loss. To this end we have generated conditional knock out mice in which the receptor is normally present during early osteoblast differentiation but inactivated upon osteoblast maturation. Bone ageing in these animals was similar to that observed for control animals. In contrast conditional ERRαKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation), but not early (commitment), negative effects of ERRα on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency.

Hydroquinone, a benzene metabolite, induces Hog1-dependent stress response signaling and causes aneuploidy in Saccharomyces cerevisiae.

PubMed

Shiga, Takeki; Suzuki, Hiroyuki; Yamamoto, Ayumi; Yamamoto, Hiroaki; Yamamoto, Kazuo

2010-01-01

Previously, we have shown that phenyl hydroquinone, a hepatic metabolite of the Ames test-negative carcinogen o-phenylphenol, efficiently induced aneuploidy in Saccharomyces cerevisiae by arresting the cell cycle at the G2/M transition as a result of the activation of the Hog1 (p38 MAPK homolog)-Swe1 (Wee1 homolog) pathway. In this experiment, we examined the aneuploidy forming effects of hydroquinone, a benzene metabolite, since both phenyl hydroquinone and hydroquinone are Ames-test negative carcinogens and share similar molecular structures. As was seen in phenyl hydroquinone, hydroquinone induced aneuploidy in yeast by delaying the cell cycle at the G2/M transition. Deficiencies in SWE1 and HOG1 abolished the hydroquinone-induced delay at the G2/M transition and aneuploidy formation. Furthermore, Hog1 was phosphorylated by hydroquinone, which may stabilize Swe1. These data indicate that the hydroquinone-induced G2/M transition checkpoint, which is activated by the Hog1-Swe1 pathway, plays a role in the formation of aneuploidy.

Dispositional and Situational Autonomy as Moderators of Mood and Creativity

ERIC Educational Resources Information Center

Xiao, Fengqiu; Wang, Ling; Chen, Yinghe; Zheng, Zhiwei; Chen, Wenjun

2015-01-01

Although previous research suggests that mood can influence creativity, the controversy about the effects of positive and negative moods has raged for years. This study investigated how the relationship between induced mood and creativity is moderated by dispositional and situational autonomy. It contrasted the different moderating effects of the…

Hearing: An Overlooked Fact in Relationship to Dyslexia.

ERIC Educational Resources Information Center

Johansen, Kjeld

Sophisticated neurological research shows that early problems with auditory perception can result in long-range negative effects for the linguistic processes in general, and such long-range effects must be assumed to be correlated with induced degenerative changes in the auditory system and perhaps in the brain's linguistic sector. This research…

Self-Discrepancies, Negative Mood States, and Compliance.

ERIC Educational Resources Information Center

Thein, Roman D.

This study examined effects of accessible self-discrepancies on subjects' mood states and the effects of these mood states on compliance. Two affective states, agitation and dejection, were induced in 115 college students by priming their available self-discrepancies. After the subjects had received specific primes and their mood states had been…

Effect of radioactive iodine-induced hypothyroidism on longitudinal bone growth during puberty in immature female rats.

PubMed

Choi, Hyeonhae; Ryu, Ki-Young; Roh, Jaesook; Bae, Jaeman

2018-05-22

Thyroid cancer in children, the most common endocrine malignancy, shows aggressive behavior and has a high recurrence rate after surgical ablation. Radioactive iodine (RAI) treatment is the most effective primary modality for medical ablation of juvenile thyroid cancer, and leads to intentional hypothyroidism. Although several negative impacts of hypothyroidism have been reported in children in response to other antithyroid agents, the combined effects of RAI exposure and hypothyroidism, on growing bones specifically, are unknown. In this study, we investigated the effect of RAI-induced hypothyroidism on the long bones during the pubertal growth spurt using immature female rats. Female Sprague-Dawley rats were randomly divided into a control group, and an RAI-treated group fed with RAI (0.37 MBq/g body weight) twice via gavage. After 4 weeks, we observed a significantly-reduced serum free thyroxine level in the RAI group. The latter group also displayed decreased body weight gain compared to the control. In addition, the lengths of long bones, such as the leg bones and vertebral column, as well as bone mineral content, were reduced in the RAI-treated animals. Our results confirm the negative impacts of RAI-induced thyroid deficiency during puberty on longitudinal bone growth and bone mineralization.

An investigation of the effect of body dissatisfaction on selective attention toward negative shape and weight-related information.

PubMed

Smith, Evelyn; Rieger, Elizabeth

2010-05-01

The aim of the present study was to investigate the effect of inducing body dissatisfaction on selective attention toward negative shape and weight-related information. A total of 54 female undergraduate university students were randomly allocated to one of three induction conditions: body dissatisfaction, negative mood, and neutral. Subsequently, participants' attentional bias toward negative shape/weight words was measured using a dot probe task. Contrary to the hypotheses, participants in the body dissatisfaction condition did not demonstrate an increase in attention toward negative shape/weight words compared with the negative mood and neutral conditions. Indeed, it was the negative mood induction that resulted in significantly increased attention toward negative shape/weight words relative to the body dissatisfaction condition. The finding that the negative mood (rather than the body dissatisfaction) induction triggered an attentional bias toward shape- and weight-related information is discussed in terms of the anxiety literature given the nature of the mood induction utilized. This finding might help to account for the high comorbidity between eating disorders and anxiety disorders and suggests the possible relevance of attentional training interventions designed for anxiety disorders in the treatment of eating disorders. 2009 by Wiley Periodicals, Inc.

BDNF-induced nitric oxide signals in cultured rat hippocampal neurons: time course, mechanism of generation, and effect on neurotrophin secretion.

PubMed

Kolarow, Richard; Kuhlmann, Christoph R W; Munsch, Thomas; Zehendner, Christoph; Brigadski, Tanja; Luhmann, Heiko J; Lessmann, Volkmar

2014-01-01

BDNF and nitric oxide signaling both contribute to plasticity at glutamatergic synapses. However, the role of combined signaling of both pathways at the same synapse is largely unknown. Using NO imaging with diaminofluoresceine in cultured hippocampal neurons we analyzed the time course of neurotrophin-induced NO signals. Application of exogenous BDNF, NT-4, and NT-3 (but not NGF) induced NO signals in the soma and in proximal dendrites of hippocampal neurons that were sensitive to NO synthase activity, TrkB signaling, and intracellular calcium elevation. The effect of NO signaling on neurotrophin secretion was analyzed in BDNF-GFP, and NT-3-GFP transfected hippocampal neurons. Exogenous application of the NO donor sodium-nitroprusside markedly inhibited neurotrophin secretion. However, endogenously generated NO in response to depolarization and neurotrophin stimulation, both did not result in a negative feedback on neurotrophin secretion. These results suggest that a negative feedback of NO signaling on synaptic secretion of neurotrophins operates only at high intracellular levels of nitric oxide that are under physiological conditions not reached by depolarization or BDNF signaling.

BDNF-induced nitric oxide signals in cultured rat hippocampal neurons: time course, mechanism of generation, and effect on neurotrophin secretion

PubMed Central

Kolarow, Richard; Kuhlmann, Christoph R. W.; Munsch, Thomas; Zehendner, Christoph; Brigadski, Tanja; Luhmann, Heiko J.; Lessmann, Volkmar

2014-01-01

BDNF and nitric oxide signaling both contribute to plasticity at glutamatergic synapses. However, the role of combined signaling of both pathways at the same synapse is largely unknown. Using NO imaging with diaminofluoresceine in cultured hippocampal neurons we analyzed the time course of neurotrophin-induced NO signals. Application of exogenous BDNF, NT-4, and NT-3 (but not NGF) induced NO signals in the soma and in proximal dendrites of hippocampal neurons that were sensitive to NO synthase activity, TrkB signaling, and intracellular calcium elevation. The effect of NO signaling on neurotrophin secretion was analyzed in BDNF-GFP, and NT-3-GFP transfected hippocampal neurons. Exogenous application of the NO donor sodium-nitroprusside markedly inhibited neurotrophin secretion. However, endogenously generated NO in response to depolarization and neurotrophin stimulation, both did not result in a negative feedback on neurotrophin secretion. These results suggest that a negative feedback of NO signaling on synaptic secretion of neurotrophins operates only at high intracellular levels of nitric oxide that are under physiological conditions not reached by depolarization or BDNF signaling. PMID:25426021

Non-thermal plasma instabilities induced by deformation of the electron energy distribution function

NASA Astrophysics Data System (ADS)

Dyatko, N. A.; Kochetov, I. V.; Napartovich, A. P.

2014-08-01

Non-thermal plasma is a key component in gas lasers, microelectronics, medical applications, waste gas cleaners, ozone generators, plasma igniters, flame holders, flow control in high-speed aerodynamics and others. A specific feature of non-thermal plasma is its high sensitivity to variations in governing parameters (gas composition, pressure, pulse duration, E/N parameter). This sensitivity is due to complex deformations of the electron energy distribution function (EEDF) shape induced by variations in electric field strength, electron and ion number densities and gas excitation degree. Particular attention in this article is paid to mechanisms of instabilities based on non-linearity of plasma properties for specific conditions: gas composition, steady-state and decaying plasma produced by the electron beam, or by an electric current pulse. The following effects are analyzed: the negative differential electron conductivity; the absolute negative electron mobility; the stepwise changes of plasma properties induced by the EEDF bi-stability; thermo-current instability and the constriction of the glow discharge column in rare gases. Some of these effects were observed experimentally and some of them were theoretically predicted and still wait for experimental confirmation.

Protective effects of piperine on lead acetate induced-nephrotoxicity in rats.

PubMed

Sudjarwo, Sri Agus; Eraiko, Koerniasari; Sudjarwo, Giftania Wardani; Koerniasari

2017-11-01

In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue. Forty male rats were divided into 5 groups: negative control (rats were given aquadest daily), positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days), and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5 th day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days). On day 65 levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) were measured. Also, kidney samples were collected for histopathological studies. The results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules) compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats. From the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats.

Inhibition of glycogen synthase kinase 3beta during heart failure is protective.

PubMed

Hirotani, Shinichi; Zhai, Peiyong; Tomita, Hideharu; Galeotti, Jonathan; Marquez, Juan Pablo; Gao, Shumin; Hong, Chull; Yatani, Atsuko; Avila, Jesús; Sadoshima, Junichi

2007-11-26

Glycogen synthase kinase (GSK)-3, a negative regulator of cardiac hypertrophy, is inactivated in failing hearts. To examine the histopathological and functional consequence of the persistent inhibition of GSK-3beta in the heart in vivo, we generated transgenic mice with cardiac-specific overexpression of dominant negative GSK-3beta (Tg-GSK-3beta-DN) and tetracycline-regulatable wild-type GSK-3beta. GSK-3beta-DN significantly reduced the kinase activity of endogenous GSK-3beta, inhibited phosphorylation of eukaryotic translation initiation factor 2B epsilon, and induced accumulation of beta-catenin and myeloid cell leukemia-1, confirming that GSK-3beta-DN acts as a dominant negative in vivo. Tg-GSK-3beta-DN exhibited concentric hypertrophy at baseline, accompanied by upregulation of the alpha-myosin heavy chain gene and increases in cardiac function, as evidenced by a significantly greater Emax after dobutamine infusion and percentage of contraction in isolated cardiac myocytes, indicating that inhibition of GSK-3beta induces well-compensated hypertrophy. Although transverse aortic constriction induced a similar increase in hypertrophy in both Tg-GSK-3beta-DN and nontransgenic mice, Tg-GSK-3beta-DN exhibited better left ventricular function and less fibrosis and apoptosis than nontransgenic mice. Induction of the GSK-3beta transgene in tetracycline-regulatable wild-type GSK-3beta mice induced left ventricular dysfunction and premature death, accompanied by increases in apoptosis and fibrosis. Overexpression of GSK-3beta-DN in cardiac myocytes inhibited tumor necrosis factor-alpha-induced apoptosis, and the antiapoptotic effect of GSK-3beta-DN was abrogated in the absence of myeloid cell leukemia-1. These results suggest that persistent inhibition of GSK-3beta induces compensatory hypertrophy, inhibits apoptosis and fibrosis, and increases cardiac contractility and that the antiapoptotic effect of GSK-3beta inhibition is mediated by myeloid cell leukemia-1. Thus, downregulation of GSK-3beta during heart failure could be compensatory.

UV-B Induced Generation of Reactive Oxygen Species Promotes Formation of BFA-Induced Compartments in Cells of Arabidopsis Root Apices

PubMed Central

Yokawa, Ken; Kagenishi, Tomoko; Baluška, František

2016-01-01

UV-B radiation is an important part of the electromagnetic spectrum emitted by the sun. For much of the period of biological evolution organisms have been exposed to UV radiation, and have developed diverse mechanisms to cope with this potential stress factor. Roots are usually shielded from exposure to UV by the surrounding soil, but may nevertheless be exposed to high energy radiation on the soil surface. Due to their high sensitivity to UV-B radiation, plant roots need to respond rapidly in order to minimize exposure on the surface. In addition to root gravitropism, effective light perception by roots has recently been discovered to be essential for triggering negative root phototropism in Arabidopsis. However, it is not fully understood how UV-B affects root growth and phototropism. Here, we report that UV-B induces rapid generation of reactive oxygen species which in turn promotes the formation of BFA-induced compartments in the Arabidopsis root apex. During unilateral UV-B irradiation of roots changes in auxin concentration on the illuminated side have been recorded. In conclusion, UV-B-induced and ROS-mediated stimulation of vesicle recycling promotes root growth and induces negative phototropism. PMID:26793199

Identification of a Raloxifene Analog That Promotes AhR-Mediated Apoptosis in Cancer Cells.

PubMed

Jang, Hyo Sang; Pearce, Martin; O'Donnell, Edmond F; Nguyen, Bach Duc; Truong, Lisa; Mueller, Monica J; Bisson, William H; Kerkvliet, Nancy I; Tanguay, Robert L; Kolluri, Siva Kumar

2017-12-01

We previously reported that raloxifene, an estrogen receptor modulator, is also a ligand for the aryl hydrocarbon receptor (AhR). Raloxifene induces apoptosis in estrogen receptor-negative human cancer cells through the AhR. We performed structure-activity studies with seven raloxifene analogs to better understand the structural requirements of raloxifene for induction of AhR-mediated transcriptional activity and apoptosis. We identified Y134 as a raloxifene analog that activates AhR-mediated transcriptional activity and induces apoptosis in MDA-MB-231 human triple negative breast cancer cells. Suppression of AhR expression strongly reduced apoptosis induced by Y134, indicating the requirement of AhR for Y134-induced apoptosis. Y134 also induced apoptosis in hepatoma cells without having an effect on cell cycle regulation. Toxicity testing on zebrafish embryos revealed that Y134 has a significantly better safety profile than raloxifene. Our studies also identified an analog of raloxifene that acts as a partial antagonist of the AhR, and is capable of inhibiting AhR agonist-induced transcriptional activity. We conclude that Y134 is a promising raloxifene analog for further optimization as an anti-cancer agent targeting the AhR.

Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy

PubMed Central

Shen, Wanxiang; Zhang, Liang; Gu, Xinsheng; Guo, Yang; Tsai, Hsiang-i; Liu, Xuewen; Li, Jian; Zhang, Jingxuan; Li, Shan; Wu, Fuyun; Liu, Ying

2017-01-01

Triple-negative breast cancers (TNBCs) are the most aggressive and hard-to-treat breast tumors with poor prognosis, and exploration for novel therapeutic drugs is impending. Arctigenin (Atn), a bioactive lignan isolated from seeds of Arctium lappa L, has been reported to inhibit many cancer types; however, the effect of Atn on TNBC remains unclear. In this study, we demonstrated that Atn decreased proliferation, and induced apoptosis in TNBC cells. Furthermore, we explored the underlying mechanism of Atn inhibition on TNBC cells. Computational docking and affinity assay showed that Atn bound to the SH2 domain of STAT3. Atn inhibited STAT3 binding to genomic DNA by disrupting hydrogen bond linking between DNA and STAT3. In addition, Atn augmented Taxotere®-induced TNBC cell cytotoxicity. TNBC xenograft tests also confirmed the antitumor effect of Atn in vivo. These characteristics render Atn as a promising candidate drug for further development and for designing new effective STAT3 inhibitors. PMID:27861147

Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy.

PubMed

Feng, Tingting; Cao, Wei; Shen, Wanxiang; Zhang, Liang; Gu, Xinsheng; Guo, Yang; Tsai, Hsiang-I; Liu, Xuewen; Li, Jian; Zhang, Jingxuan; Li, Shan; Wu, Fuyun; Liu, Ying

2017-01-03

Triple-negative breast cancers (TNBCs) are the most aggressive and hard-to-treat breast tumors with poor prognosis, and exploration for novel therapeutic drugs is impending. Arctigenin (Atn), a bioactive lignan isolated from seeds of Arctium lappa L, has been reported to inhibit many cancer types; however, the effect of Atn on TNBC remains unclear. In this study, we demonstrated that Atn decreased proliferation, and induced apoptosis in TNBC cells. Furthermore, we explored the underlying mechanism of Atn inhibition on TNBC cells. Computational docking and affinity assay showed that Atn bound to the SH2 domain of STAT3. Atn inhibited STAT3 binding to genomic DNA by disrupting hydrogen bond linking between DNA and STAT3. In addition, Atn augmented Taxotere®-induced TNBC cell cytotoxicity. TNBC xenograft tests also confirmed the antitumor effect of Atn in vivo. These characteristics render Atn as a promising candidate drug for further development and for designing new effective STAT3 inhibitors.

Current major depression is associated with greater sensitivity to the motivational effect of both negative mood induction and abstinence on tobacco-seeking behavior.

PubMed

Hogarth, Lee; Mathew, Amanda R; Hitsman, Brian

2017-07-01

Although depression and smoking commonly co-occur, the mechanisms underpinning this association are poorly understood. One hypothesis is that depression promotes tobacco dependence, persistence and relapse by increasing sensitivity to acute negative mood and abstinence induced tobacco-seeking behavior. Twenty nine daily smokers of >10 cigarettes per day, nine with major depression and 20 without, completed two laboratory sessions one week apart, smoking as normal prior to session 1 (sated session), and 6h abstinent prior to session 2 (abstinent session). In both sessions, tobacco-seeking was measured at baseline by preference to view smoking versus food images. Negative mood was then induced by negative ruminative statements and sad music, before tobacco-seeking was measured again at test. In the sated session, negative mood induction produced a greater increase in tobacco choice from baseline to test in depressed (p<0.001, η p 2 =0.782) compared to non-depressed smokers (p=0.045, η p 2 =0.216, interaction: p=0.046, η p 2 =0.150). Abstinence also produced a greater increase in baseline tobacco choice between the sated and abstinent sessions in depressed (p=0.002, η p 2 =0.771) compared to non-depressed smokers (p=0.22, η p 2 =0.089, interaction: p=0.023, η p 2 =0.189). These mood and abstinence induced increases in tobacco choice were positively associated with depression symptoms across the sample as a whole (ps≤0.04, η p 2 ≥0.159), and correlated with each other (r=0.67, p<0.001). Current major depression or depression symptoms may promote tobacco dependence, persistence and relapse by increasing sensitivity to both acute negative mood and abstinence induced tobacco-seeking behavior. Treatments should seek to break the association between adverse states and smoking to cope. Copyright © 2017 Elsevier B.V. All rights reserved.

How Psychological Stress Affects Emotional Prosody.

PubMed

Paulmann, Silke; Furnes, Desire; Bøkenes, Anne Ming; Cozzolino, Philip J

2016-01-01

We explored how experimentally induced psychological stress affects the production and recognition of vocal emotions. In Study 1a, we demonstrate that sentences spoken by stressed speakers are judged by naïve listeners as sounding more stressed than sentences uttered by non-stressed speakers. In Study 1b, negative emotions produced by stressed speakers are generally less well recognized than the same emotions produced by non-stressed speakers. Multiple mediation analyses suggest this poorer recognition of negative stimuli was due to a mismatch between the variation of volume voiced by speakers and the range of volume expected by listeners. Together, this suggests that the stress level of the speaker affects judgments made by the receiver. In Study 2, we demonstrate that participants who were induced with a feeling of stress before carrying out an emotional prosody recognition task performed worse than non-stressed participants. Overall, findings suggest detrimental effects of induced stress on interpersonal sensitivity.

How Psychological Stress Affects Emotional Prosody

PubMed Central

Paulmann, Silke; Furnes, Desire; Bøkenes, Anne Ming; Cozzolino, Philip J.

2016-01-01

We explored how experimentally induced psychological stress affects the production and recognition of vocal emotions. In Study 1a, we demonstrate that sentences spoken by stressed speakers are judged by naïve listeners as sounding more stressed than sentences uttered by non-stressed speakers. In Study 1b, negative emotions produced by stressed speakers are generally less well recognized than the same emotions produced by non-stressed speakers. Multiple mediation analyses suggest this poorer recognition of negative stimuli was due to a mismatch between the variation of volume voiced by speakers and the range of volume expected by listeners. Together, this suggests that the stress level of the speaker affects judgments made by the receiver. In Study 2, we demonstrate that participants who were induced with a feeling of stress before carrying out an emotional prosody recognition task performed worse than non-stressed participants. Overall, findings suggest detrimental effects of induced stress on interpersonal sensitivity. PMID:27802287

Enhanced emotion-induced amnesia in borderline personality disorder

PubMed Central

HURLEMANN, RENÉ; HAWELLEK, BARBARA; MAIER, WOLFGANG; DOLAN, RAYMOND J.

2009-01-01

Background Current biological concepts of borderline personality disorder (BPD) emphasize the interference of emotional hyperarousal and cognitive functions. A prototypical example is episodic memory. Pre-clinical investigations of emotion–episodic memory interactions have shown specific retrograde and anterograde episodic memory changes in response to emotional stimuli. These changes are amygdala dependent and vary as a function of emotional arousal and valence. Method To determine whether there is amygdala hyper-responsiveness to emotional stimuli as the underlying pathological substrate of cognitive dysfunction in BPD, 16 unmedicated female patients with BPD were tested on the behavioural indices of emotion-induced amnesia and hypermnesia established in 16 healthy controls. Results BPD patients displayed enhanced retrograde and anterograde amnesia in response to presentation of negative stimuli, while positive stimuli elicited no episodic memory-modulating effects. Conclusion These findings suggest that an amygdala hyper-responsiveness to negative stimuli may serve as a crucial aetiological contributor to emotion-induced cognitive dysfunction in BPD. PMID:17224096

Silicon and Rhizophagus irregularis: potential candidates for ameliorating negative impacts of arsenate and arsenite stress on growth, nutrient acquisition and productivity in Cajanus cajan (L.) Millsp. genotypes.

PubMed

Garg, Neera; Kashyap, Lakita

2017-08-01

Arsenic (As) gets accumulated in plants via phosphorous transporters and water channels and interferes with nutrient and water uptake, adversely affecting growth and productivity. Although, Si and AM have been reported to combat arsenic stress, their comparative and interactive roles in ameliorating As V and As III toxicities have not been reported. Study evaluated effects of Si and Rhizophagus irregularis on growth, As uptake and yield under arsenate and arsenite stress in two pigeonpea genotypes (metal tolerant-Pusa 2002 and metal sensitive-Pusa 991). Higher As accumulation and translocation was observed in As III treated roots of Pusa 991 than those of Pusa 2002 when compared with As V. Roots were more negatively affected than shoots which led to a significant decline in nutrient uptake, leaf chlorophylls, and yield, with As III inducing more negative effects. Pusa 2002 established more effective mycorrhizal symbiosis and had higher biomass than Pusa 991. Si was more effective in inducing shoot biomass while AM inoculation significantly improved root biomass. AM enhanced Si uptake in roots and leaves in a genotype dependent manner. Combined application of Si and AM were highly beneficial in improving leaf water status, chlorophyll pigments, biomass, and productivity. Complete amelioration of negative impacts of both concentrations of As V and lower concentration of As III were recorded under +Si +AM in Pusa 2002. Results highlighted great potential of Si in improving growth and productivity of pigeonpea through R. irregularis under As V and As III stresses.

Anti-proliferation of triple-negative breast cancer cells with physagulide P: ROS/JNK signaling pathway induces apoptosis and autophagic cell death

PubMed Central

Gao, Cai-Yun; Ma, Ting; Zhang, Hao; Zhou, Miao-Miao; Yang, Yan-Wei; Yang, Lei; Kong, Ling-Yi

2017-01-01

Physagulide P (PP), a new natural compound, was isolated from Physalis angulate L. in our laboratory. In this study, we demonstrated that PP potently suppressed cell proliferation by inducing G2/M phase arrest in MDA-MB-231 and MDA-MB-468 cells. Moreover, PP provoked apoptosis by decreasing the mitochondrial membrane potential and elevating the Bax/Bcl-2 protein expression ratio. The caspase inhibitor Z-VAD-FMK partly restore cell viability, suggesting that apoptosis plays as an important role in the anti-proliferative effect of PP. PP-treated cells also underwent autophagy, as evidenced by the formation of autophagosomes and the accumulation of LC3BII. Furthermore, the knockdown of LC3B reduced PP-induced cytotoxicity, indicating that autophagy played an anticancer effect. PP also induced the generation of reactive oxygen species (ROS) and resulted in c-Jun N-terminal kinases (JNK) activation. Accordingly, JNK siRNA significantly attenuated PP-triggered apoptosis and autophagy, and ROS scavengers almost completely reverse this apoptosis and autophagy. The ROS scavenger also blocked PP-induced G2/M phase arrest and the phosphorylation of JNK. Our results revealed that PP induced G2/M phase arrest, apoptosis and autophagy via the ROS/JNK signaling pathway in MDA-MB-231 and MDA-MB-468 cells. Therefore, PP is a promising candidate for the development of antitumor drugs for the treatment of triple-negative breast cancer. PMID:28969050

Tumor dormancy and cell signaling. II. Antibody as an agonist in inducing dormancy of a B cell lymphoma in SCID mice.

PubMed

Racila, E; Scheuermann, R H; Picker, L J; Yefenof, E; Tucker, T; Chang, W; Marches, R; Street, N E; Vitetta, E S; Uhr, J W

1995-04-01

Tumor dormancy can be induced in a murine B cell lymphoma (BCL1) by immunizing BALB/c mice with the tumor immunoglobulin (Ig) before tumor cell challenge. In this report, we have investigated the immunological and cellular mechanisms underlying the induction of dormancy. BCL1 tumor cells were injected into SCID mice passively immunized with antibody against different epitopes on IgM or IgD with or without idiotype (Id)-immune T lymphocytes. Results indicate that antibody to IgM is sufficient to induce a state of dormancy. Antibodies against other cell surface molecules including IgD and CD44 (Pgp1) had no effect on tumor growth. Id-immune T cells by themselves also had no effect on tumor growth in SCID mice. However, simultaneous transfer of anti-Id and Id-immune T cells enhanced both the induction and duration of the dormant state. In vitro studies indicated that antibody to IgM induced apoptosis within several hours and cell cycle arrest by 24 h. Hyper cross-linking increased apoptosis. The Fc gamma RII receptor played little or no role in the negative signaling. Antibodies that did not negatively signal in vitro did not induce dormancy in vivo. The results suggest that anti-IgM plays a decisive role in inducing tumor dormancy to BCL1 by acting as an agonist of IgM-mediated signal transduction pathways.

GPER negatively regulates TNFα-induced IL-6 production in human breast cancer cells via NF-κB pathway.

PubMed

Okamoto, Mariko; Mizukami, Yoichi

2016-05-31

Estrogen is known to have anti-inflammatory effects, that are thought to be mediated by the classical estrogen receptors (ERs), ERα and ERβ. G protein coupled estrogen receptor1 (GPER) is a novel membrane-type estrogen receptor that can mediate non-genomic estrogenic responses. Although there have been several reports asserting that the participation of GPER in anti-inflammatory effects is induced by estrogen, the role of GPER remains poorly understood. In this study, we investigated the involvement of GPER in the regulation of a representative inflammatory cytokine, IL-6. We first examined the expression of IL-6 mRNA by TNFα stimulation in the transfection of GPER-expression plasmid into HeLa cells. Exogenous GPER significantly inhibited TNFα-induced IL-6 expression, and blocked NF-κB promoter activity inducing the expression of IL-6 in a dose-dependent manner. The promoter activity was restored almost to control level by transfection with the C-terminal deletion mutant of GPER. Similar results have been observed in endogenous GPER using SKBR3 cells which do not express the classical ERs. The data have been validated by treatment of GPER with siRNA. These findings indicate that GPER negatively regulates TNFα-induced IL-6 expression, probably through inhibition of NF-κB promoter activity by a signal(s) derived from the C-terminal region of GPER.

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.

Ocean acidification ameliorates harmful effects of warming in primary consumer.

PubMed

Pedersen, Sindre Andre; Hanssen, Anja Elise

2018-01-01

Climate change-induced warming and ocean acidification are considered two imminent threats to marine biodiversity and current ecosystem structures. Here, we have for the first time examined an animal's response to a complete life cycle of exposure to co-occurring warming (+3°C) and ocean acidification (+1,600 μatm CO 2 ), using the key subarctic planktonic copepod, Calanus finmarchicus , as a model species. The animals were generally negatively affected by warming, which significantly reduced the females' energy status and reproductive parameters (respectively, 95% and 69%-87% vs. control). Unexpectedly, simultaneous acidification partially offset the negative effect of warming in an antagonistic manner, significantly improving reproductive parameters and hatching success (233%-340% improvement vs. single warming exposure). The results provide proof of concept that ocean acidification may partially offset negative effects caused by warming in some species. Possible explanations and ecological implications for the observed antagonistic effect are discussed.

Negative Mood State Enhances the Susceptibility to Unpleasant Events: Neural Correlates from a Music-Primed Emotion Classification Task

PubMed Central

Yuan, Jiajin; Chen, Jie; Yang, Jiemin; Ju, Enxia; Norman, Greg J.; Ding, Nanxiang

2014-01-01

Background Various affective disorders are linked with enhanced processing of unpleasant stimuli. However, this link is likely a result of the dominant negative mood derived from the disorder, rather than a result of the disorder itself. Additionally, little is currently known about the influence of mood on the susceptibility to emotional events in healthy populations. Method Event-Related Potentials (ERP) were recorded for pleasant, neutral and unpleasant pictures while subjects performed an emotional/neutral picture classification task during positive, neutral, or negative mood induced by instrumental Chinese music. Results Late Positive Potential (LPP) amplitudes were positively related to the affective arousal of pictures. The emotional responding to unpleasant pictures, indicated by the unpleasant-neutral differences in LPPs, was enhanced during negative compared to neutral and positive moods in the entire LPP time window (600–1000 ms). The magnitude of this enhancement was larger with increasing self-reported negative mood. In contrast, this responding was reduced during positive compared to neutral mood in the 800–1000 ms interval. Additionally, LPP reactions to pleasant stimuli were similar across positive, neutral and negative moods except those in the 800–900 ms interval. Implications Negative mood intensifies the humans' susceptibility to unpleasant events in healthy individuals. In contrast, music-induced happy mood is effective in reducing the susceptibility to these events. Practical implications of these findings were discussed. PMID:24587070

The effect of mild acute stress during memory consolidation on emotional recognition memory.

PubMed

Corbett, Brittany; Weinberg, Lisa; Duarte, Audrey

2017-11-01

Stress during consolidation improves recognition memory performance. Generally, this memory benefit is greater for emotionally arousing stimuli than neutral stimuli. The strength of the stressor also plays a role in memory performance, with memory performance improving up to a moderate level of stress and thereafter worsening. As our daily stressors are generally minimal in strength, we chose to induce mild acute stress to determine its effect on memory performance. In the current study, we investigated if mild acute stress during consolidation improves memory performance for emotionally arousing images. To investigate this, we had participants encode highly arousing negative, minimally arousing negative, and neutral images. We induced stress using the Montreal Imaging Stress Task (MIST) in half of the participants and a control task to the other half of the participants directly after encoding (i.e. during consolidation) and tested recognition 48h later. We found no difference in memory performance between the stress and control group. We found a graded pattern among confidence, with responders in the stress group having the least amount of confidence in their hits and controls having the most. Across groups, we found highly arousing negative images were better remembered than minimally arousing negative or neutral images. Although stress did not affect memory accuracy, responders, as defined by cortisol reactivity, were less confident in their decisions. Our results suggest that the daily stressors humans experience, regardless of their emotional affect, do not have adverse effects on memory. Copyright © 2017 Elsevier Inc. All rights reserved.

Old and in pain: Enduring and situational effects of cultural aging stereotypes on older people's pain experiences.

PubMed

Bernardes, S F; Marques, S; Matos, M

2015-08-01

This study aimed to investigate the interplay between enduring and situational aging stereotype (AS) effects in older adults' self-reports of clinical and experimentally induced pain. We expected that, as compared with the situational activation of positive AS or a neutral condition, the activation of negative AS would lead to more severe self-reports of clinical pain (H1, hypothesis 1), higher cold pressor task (CPT) pain threshold (H2) and lower CPT pain tolerance (H3), especially among older adults who more strongly endorsed AS. This was a prospective study across two moments in time. At time 1 (T1), 52 older adults (Mage  = 74.7; 51.9% women) filled out measures of cultural AS endorsement, clinical pain severity and interference. Three months afterwards (T2), some of these participants collaborated in an experimental study on the effects of AS activation on reported clinical pain (n = 40) and experimentally induced (using CPT) pain threshold and tolerance (n = 35). Our results supported H2, i.e., as compared with the activation of positive AS or a neutral condition, when negative AS were activated older adults showed higher CPT pain thresholds, but this effect was more salient among those who more strongly endorsed AS at T1. This study stresses the influence of cultural AS in older adults' pain experiences showing that the situational activation of negative AS greatly increases experimentally induced pain thresholds of elders who more strongly endorse those stereotypes. It also highlights the relevance of interventions at the level of the physical and/or social environments surrounding elders in pain. © 2014 European Pain Federation - EFIC®

Soyabean glycinin depresses intestinal growth and function in juvenile Jian carp (Cyprinus carpio var Jian): protective effects of glutamine.

PubMed

Jiang, Wei-Dan; Hu, Kai; Zhang, Jin-Xiu; Liu, Yang; Jiang, Jun; Wu, Pei; Zhao, Juan; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Feng, Lin

2015-11-28

This study investigated the effects of glycinin on the growth, intestinal oxidative status, tight junction components, cytokines and apoptosis signalling factors of fish. The results showed that an 80 g/kg diet of glycinin exposure for 42 d caused poor growth performance and depressed intestinal growth and function of juvenile Jian carp (Cyprinus carpio var. Jian). Meanwhile, dietary glycinin exposure induced increases in lipid peroxidation and protein oxidation; it caused reductions in superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities; and it increased MnSOD, CuZnSOD, GPx1b and GPx4a mRNA levels, suggesting an adaptive mechanism against stress in the intestines of fish. However, dietary glycinin exposure decreased both the activity and mRNA levels of nine isoforms of glutathione-S-transferase (GST) (α, μ, π, ρ, θ, κ, mGST1, mGST2 and mGST3), indicating toxicity to this enzyme activity and corresponding isoform gene expressions. In addition, glycinin exposure caused partial disruption of intestinal cell-cell tight junction components, disturbances of cytokines and induced apoptosis signalling in the distal intestines>mid intestines>proximal intestines of fish. Glycinin exposure also disturbed the mRNA levels of intestinal-related signalling factors Nrf2, Keap1a, Keap1b, eleven isoforms of protein kinase C and target of rapamycin/4E-BP. Interestingly, glutamine was observed to partially block those negative influences. In conclusion, this study indicates that dietary glycinin exposure causes intestinal oxidative damage and disruption of intestinal physical barriers and functions and reduces fish growth, but glutamine can reverse those negative effects in fish. This study provides some information on the mechanism of glycinin-induced negative effects.

Effects of zolpidem and zopiclone on cognitive and attentional function in young healthy volunteers: an event-related potential study.

PubMed

Nakajima, T; Takazawa, S; Hayashida, S; Nakagome, K; Sasaki, T; Kanno, O

2000-02-01

The effects of zolpidem and zopiclone, non-benzodiazepine ultra-short-acting hypnotics, on cognitive function and vigilance level were investigated in the morning following nocturnal administration using event-related potentials (ERP) and a sleep latency test (SLT). Zopiclone significantly shortened the sleep latency the following morning, whereas zolpidem did not, perhaps due to the difference in the elimination half-lives between the compounds. No significant effect was observed for either drug on the ERP indices, including the P3, mismatch negativity and negative difference components. At a clinically prescribed dosage these sleep inducers have no remarkable effect on cognitive or attentional functions but increase sleepiness of the subjects.

CREB activity in dopamine D1 receptor expressing neurons regulates cocaine-induced behavioral effects

PubMed Central

Bilbao, Ainhoa; Rieker, Claus; Cannella, Nazzareno; Parlato, Rosanna; Golda, Slawomir; Piechota, Marcin; Korostynski, Michal; Engblom, David; Przewlocki, Ryszard; Schütz, Günther; Spanagel, Rainer; Parkitna, Jan R.

2014-01-01

It is suggested that striatal cAMP responsive element binding protein (CREB) regulates sensitivity to psychostimulants. To test the cell-specificity of this hypothesis we examined the effects of a dominant-negative CREB protein variant expressed in dopamine receptor D1 (D1R) neurons on cocaine-induced behaviors. A transgenic mouse strain was generated by pronuclear injection of a BAC-derived transgene harboring the A-CREB sequence under the control of the D1R gene promoter. Compared to wild-type, drug-naïve mutants showed moderate alterations in gene expression, especially a reduction in basal levels of activity-regulated transcripts such as Arc and Egr2. The behavioral responses to cocaine were elevated in mutant mice. Locomotor activity after acute treatment, psychomotor sensitization after intermittent drug injections and the conditioned locomotion after saline treatment were increased compared to wild-type littermates. Transgenic mice had significantly higher cocaine conditioned place preference, displayed normal extinction of the conditioned preference, but showed an augmented cocaine-seeking response following priming-induced reinstatement. This enhanced cocaine-seeking response was associated with increased levels of activity-regulated transcripts and prodynorphin. The primary reinforcing effects of cocaine were not altered in the mutant mice as they did not differ from wild-type in cocaine self-administration under a fixed ratio schedule at the training dose. Collectively, our data indicate that expression of a dominant-negative CREB variant exclusively in neurons expressing D1R is sufficient to recapitulate the previously reported behavioral phenotypes associated with virally expressed dominant-negative CREB. PMID:24966820

HIV envelope-mediated, CCR5/α4β7-dependent killing of CD4-negative γδ T cells which are lost during progression to AIDS.

PubMed

Li, Haishan; Pauza, C David

2011-11-24

HIV infects and replicates in CD4+ T cells but effects on host immunity and disease also involve depletion, hyper-activation, and modification of CD4-negative cell populations. In particular, the depletion of CD4-negative γδ T cells is common to all HIV+ individuals. We found that soluble or cell-associated envelope glycoproteins from CCR5-tropic strains of HIV could bind, activates the p38-caspase pathway, and induce the death of γδ cells. Envelope binding requires integrin α4β7 and chemokine receptor CCR5 which are at high levels and form a complex on the γδ T cell membrane. This receptor complex facilitated V3 loop binding to CCR5 in the absence of CD4-induced conformational changes. Cell death was increased by antigen stimulation after exposure to envelope glycoprotein. Direct signaling by envelope glycoprotein killed CD4-negative γδ T cells and reproduced a defect observed in all patients with HIV disease.

Effects of appraisal training on responses to a distressing autobiographical event.

PubMed

Woud, Marcella L; Zlomuzica, Armin; Cwik, Jan C; Margraf, Jürgen; Shkreli, Lorika; Blackwell, Simon E; Gladwin, Thomas E; Ehring, Thomas

2018-04-14

Dysfunctional appraisals are a key factor suggested to be involved in the development and maintenance of PTSD. Research has shown that experimental induction of a positive or negative appraisal style following a laboratory stressor affects analogue posttraumatic stress symptoms. This supports a causal role of appraisal in the development of traumatic stress symptoms and the therapeutic promise of modifying appraisals to reduce PTSD symptoms. The present study aimed to extend previous findings by investigating the effects of experimentally induced appraisals on reactions to a naturally occurring analogue trauma and by examining effects on both explicit and implicit appraisals. Participants who had experienced a distressing life event were asked to imagine themselves in the most distressing moment of that event and then received either a positive or negative Cognitive Bias Modification training targeting appraisals (CBM-App). The CBM-App training induced training-congruent appraisals, but group differences in changes in appraisal over training were only seen for explicit and not implicit appraisals. However, participants trained positively reported less intrusion distress over the subsequent week than those trained negatively, and lower levels of overall posttraumatic stress symptoms. These data support the causal relationship between appraisals and trauma distress, and further illuminate the mechanisms linking the two. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of Self-Image on Anxiety, Judgement Bias and Emotion Regulation in Social Anxiety Disorder.

PubMed

Lee, Hannah; Ahn, Jung-Kwang; Kwon, Jung-Hye

2018-04-25

Research to date has focused on the detrimental effects of negative self-images for individuals with social anxiety disorder (SAD), but the benefits of positive self-images have been neglected. The present study examined the effect of holding a positive versus negative self-image in mind on anxiety, judgement bias and emotion regulation (ER) in individuals with SAD. Forty-two individuals who met the diagnostic criteria for SAD were randomly assigned to either a positive or a negative self-image group. Participants were assessed twice with a week's interval in between using the Reactivity and Regulation Situation Task, which measures social anxiety, discomfort, judgement bias and ER, prior to and after the inducement of a positive or negative self-image. Individuals in the positive self-image group reported less social anxiety, discomfort and distress from social cost when compared with their pre-induction state. They also used more adaptive ER strategies and experienced less anxiety and discomfort after using ER. In contrast, individuals in the negative self-image group showed no significant differences in anxiety, judgement bias or ER strategies before and after the induction. This study highlights the beneficial effects of positive self-images on social anxiety and ER.

Effect of X-ray irradiation on the optical absorption of СdSe1-xTex nanocrystals embedded in borosilicate glass

NASA Astrophysics Data System (ADS)

Prymak, M. V.; Azhniuk, Yu. M.; Solomon, A. M.; Krasilinets, V. M.; Lopushansky, V. V.; Bodnar, I. V.; Gomonnai, A. V.; Zahn, D. R. T.

2012-07-01

The effect of X-ray irradiation on the optical absorption spectra of CdSe1-xTex nanocrystals embedded in a borosilicate matrix is studied. The observed blue shift of the absorption edge and bleaching of the confinement-related features in the spectra are related to X-ray induced negative ionization of the nanocrystals with charge transfer across the nanocrystal/matrix interface. The radiation-induced changes are observed to recover after longer post-irradiation storage at room temperature.

Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to reactivate protein phosphatase 2A.

PubMed

Huang, Qiuyue; Qin, Shanshan; Yuan, Xiaoning; Zhang, Liang; Ji, Juanli; Liu, Xuewen; Ma, Wenjing; Zhang, Yunfei; Liu, Pengfei; Sun, Zhiting; Zhang, Jingxuan; Liu, Ying

2017-07-01

We have shown that a novel STAT3 inhibitor arctigenin (Atn) induces significant cytotoxicity in triple-negative breast cancer (TNBC) cells. This study further delineated molecular mechanisms where by Atn triggered cytotoxicity in TNBC cells. We found Atn can also inhibit metastasis in TNBC cells through cancerous inhibitor of protein phosphatase 2A (CIP2A) pathway. CIP2A is an endogenous inhibitor of protein phosphatase 2A (PP2A), which can increase the migration and invasion of various cancer cells. PP2A is a tumor suppressor, which is functionally defective in various cancers. Atn-induced metastasis inhibition was associated with reactivation of PP2A, downregulation of CIP2A and Akt phosphorylation. Silencing CIP2A enhanced Atn-induced metastasis inhibition and apoptosis in TNBCs. Furthermore, ectopic expression of CIP2A or inhibition of PP2A in TNBC cells abolished the effects of Atn. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A, at least in part, promotes the anti-metastasis effect induced by Atn. Our findings disclose the novel therapeutic mechanism of this targeted agent, and suggest the therapeutic potential and feasibility of developing PP2A enhancers as a novel anticancer strategy.

Specifying the effects of physician's communication on patients' outcomes: A randomised controlled trial.

PubMed

van Osch, Mara; van Dulmen, Sandra; van Vliet, Liesbeth; Bensing, Jozien

2017-08-01

To experimentally test the effects of physician's affect-oriented communication and inducing expectations on outcomes in patients with menstrual pain. Using a 2×2 RCT design, four videotaped simulated medical consultations were used, depicting a physician and a patient with menstrual pain. In the videos, two elements of physician's communication were manipulated: (1) affect-oriented communication (positive: warm, emphatic; versus negative: cold, formal), and (2) outcome expectation induction (positive versus uncertain). Participants (293 women with menstrual pain), acting as analogue patients, viewed one of the four videos. Pre- and post video participants' outcomes (anxiety, mood, self-efficacy, outcome expectations, and satisfaction) were assessed. Positive affect-oriented communication reduced anxiety (p<0.001), negative mood (p=0.001), and increased satisfaction (p<0.001) compared to negative affect-oriented communication. Positive expectations increased feelings of self-efficacy (p<0.001) and outcome expectancies (p<0.001), compared to uncertain expectations, but did not reduce anxiety. The combination of positive affect-oriented communication and a positive expectation reduced anxiety (p=0.02), increased outcome expectancies (p=0.01) and satisfaction (p=0.001). Being empathic and inducing positive expectations have distinct and combined effects, demonstrating that both are needed to influence patients' outcomes for the best. Continued medical training is needed to harness placebo-effects of medical communication into practice. Copyright © 2017 Elsevier B.V. All rights reserved.

On the persistence of cocaine-induced place preferences and aversions in rats

PubMed Central

Su, Zu-In; Santoostaroam, Ashley; Wenzel, Jennifer; Ettenberg, Aaron

2013-01-01

Rationale Rats develop preferences for places associated with the immediate rewarding effects of cocaine and aversions for places paired with the drug’s delayed negative effects. The motivation to seek cocaine should therefore depend upon the relative magnitude of these two opposing effects of the drug. Objective The current study tested this notion by assessing the relative persistence of the positive and negative associations formed between environmental cues and the immediate or delayed effects of cocaine. Methods Rats were administered 1.0 mg/kg intravenous cocaine and placed into a distinctive environment either immediately or 15-min after injection, alternating daily with pairings of a second environment with saline. After 4 drug- and 4 saline-place pairings, rats were returned to their home cages for 1, 7 or 21 days after which a 15-min place preference test was conducted. In a second experiment, the effectiveness of a single reconditioning session (one drug-place and one saline-place pairing) to reactivate learned cocaine-place associations was assessed after 1- or 3-weeks of drug abstinence. Results Places associated with the immediate effects of cocaine were preferred (CPP), while places associated with the delayed effects of cocaine were avoided (CPA). The persistence of these effects differed with CPP remaining viable at 3-weeks of withdrawal while CPA was no longer present after 1-week. Reconditioning with an additional cocaine-place pairing failed to reinstate the CPA. Conclusions Cue-induced “relapse” of cocaine-seeking behavior may be fueled in part by an increased persistence of positive relative to negative associations with drug-paired stimuli. PMID:23568579

Antimicrobial effects of lysophosphatidylcholine on methicillin-resistant Staphylococcus aureus.

PubMed

Miyazaki, Haruko; Midorikawa, Naoko; Fujimoto, Saki; Miyoshi, Natsumi; Yoshida, Hideto; Matsumoto, Tetsuya

2017-07-01

Methicillin-resistant Staphylococcus aureus (MRSA) is an important health care-associated and community-associated pathogen and causes a large number of infections worldwide. For the purpose of application to topical treatment of MRSA infection, we examined the antimicrobial effects of lysophosphatidylcholine (LPC) on MRSA strains. We also investigated the combination effect of LPC and gentamicin on MRSA growth. The LPC minimum inhibitory concentrations (MIC) for Gram-positive ( S. aureus, Staphylococcus epidermidis , and Streptococcus pneumoniae ) and Gram-negative ( Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae , and Pseudomonas aeruginosa ) bacteria were measured by the broth microdilution method. The mechanism of LPC-mediated MRSA killing was investigated by membrane permeability analysis with DiSC3(5) fluorescence and growth curve analysis. Lastly, the effects of LPC on gentamicin-induced bactericidal activity were determined in combination treatment studies with 15 gentamicin-resistant MRSA isolates from the skin, nose, or ears. The LPC MIC for Gram-positive bacteria varied between 32 µg/ml and >2048 µg/ml, whereas that for all Gram-negative bacteria was >2048 µg/ml. Consistently, membrane permeability analysis showed that LPC was substantially more effective in inducing membrane permeability in Gram-positive bacteria than in Gram-negative counterparts. Growth curve analysis in cotreatment studies demonstrated that LPC has intrinsic bactericidal effects and can also potentiate gentamicin sensitivity in resistant MRSA strains. Our study demonstrates that LPC exhibits intrinsic antimicrobial effects and can enhance the antimicrobial effects of gentamicin for resistant MRSA strains, suggesting that LPC may be a beneficial additive in topical antibiotics for superficial skin infections.

Antimicrobial effects of lysophosphatidylcholine on methicillin-resistant Staphylococcus aureus

PubMed Central

Miyazaki, Haruko; Midorikawa, Naoko; Fujimoto, Saki; Miyoshi, Natsumi; Yoshida, Hideto; Matsumoto, Tetsuya

2017-01-01

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is an important health care-associated and community-associated pathogen and causes a large number of infections worldwide. For the purpose of application to topical treatment of MRSA infection, we examined the antimicrobial effects of lysophosphatidylcholine (LPC) on MRSA strains. We also investigated the combination effect of LPC and gentamicin on MRSA growth. Methods: The LPC minimum inhibitory concentrations (MIC) for Gram-positive (S. aureus, Staphylococcus epidermidis, and Streptococcus pneumoniae) and Gram-negative (Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa) bacteria were measured by the broth microdilution method. The mechanism of LPC-mediated MRSA killing was investigated by membrane permeability analysis with DiSC3(5) fluorescence and growth curve analysis. Lastly, the effects of LPC on gentamicin-induced bactericidal activity were determined in combination treatment studies with 15 gentamicin-resistant MRSA isolates from the skin, nose, or ears. Results: The LPC MIC for Gram-positive bacteria varied between 32 µg/ml and >2048 µg/ml, whereas that for all Gram-negative bacteria was >2048 µg/ml. Consistently, membrane permeability analysis showed that LPC was substantially more effective in inducing membrane permeability in Gram-positive bacteria than in Gram-negative counterparts. Growth curve analysis in cotreatment studies demonstrated that LPC has intrinsic bactericidal effects and can also potentiate gentamicin sensitivity in resistant MRSA strains. Conclusions: Our study demonstrates that LPC exhibits intrinsic antimicrobial effects and can enhance the antimicrobial effects of gentamicin for resistant MRSA strains, suggesting that LPC may be a beneficial additive in topical antibiotics for superficial skin infections. PMID:28748087

Negative quantum capacitance induced by midgap states in single-layer graphene.

PubMed

Wang, Lin; Wang, Yang; Chen, Xiaolong; Zhu, Wei; Zhu, Chao; Wu, Zefei; Han, Yu; Zhang, Mingwei; Li, Wei; He, Yuheng; Xiong, Wei; Law, Kam Tuen; Su, Dangsheng; Wang, Ning

2013-01-01

We demonstrate that single-layer graphene (SLG) decorated with a high density of Ag adatoms displays the unconventional phenomenon of negative quantum capacitance. The Ag adatoms act as resonant impurities and form nearly dispersionless resonant impurity bands near the charge neutrality point (CNP). Resonant impurities quench the kinetic energy and drive the electrons to the Coulomb energy dominated regime with negative compressibility. In the absence of a magnetic field, negative quantum capacitance is observed near the CNP. In the quantum Hall regime, negative quantum capacitance behavior at several Landau level positions is displayed, which is associated with the quenching of kinetic energy by the formation of Landau levels. The negative quantum capacitance effect near the CNP is further enhanced in the presence of Landau levels due to the magnetic-field-enhanced Coulomb interactions.

Negative Quantum Capacitance Induced by Midgap States in Single-layer Graphene

PubMed Central

Wang, Lin; Wang, Yang; Chen, Xiaolong; Zhu, Wei; Zhu, Chao; Wu, Zefei; Han, Yu; Zhang, Mingwei; Li, Wei; He, Yuheng; Xiong, Wei; Law, Kam Tuen; Su, Dangsheng; Wang, Ning

2013-01-01

We demonstrate that single-layer graphene (SLG) decorated with a high density of Ag adatoms displays the unconventional phenomenon of negative quantum capacitance. The Ag adatoms act as resonant impurities and form nearly dispersionless resonant impurity bands near the charge neutrality point (CNP). Resonant impurities quench the kinetic energy and drive the electrons to the Coulomb energy dominated regime with negative compressibility. In the absence of a magnetic field, negative quantum capacitance is observed near the CNP. In the quantum Hall regime, negative quantum capacitance behavior at several Landau level positions is displayed, which is associated with the quenching of kinetic energy by the formation of Landau levels. The negative quantum capacitance effect near the CNP is further enhanced in the presence of Landau levels due to the magnetic-field-enhanced Coulomb interactions. PMID:23784258

Asymmetric effects of positive and negative affect on decision making.

PubMed

Cahir, Caitriona; Thomas, Kevin

2010-02-01

Although affect is a fundamental element of decision making, there are different theoretical accounts and conflicting empirical evidence of its influence. This experiment was done to begin a more coherent account of the influence of affect by using standardised images to induce affect and a betting task to measure decision making. Eighty-five participants were assigned to a positive, a negative, or a neutral affect condition before making decisions on two hypothetical horse races. Analysis indicated that those in the positive and negative conditions made lower-risk decisions than those in the neutral condition; however, this did not differ between the races, suggesting that task familiarity did not moderate the influence of affect. Contrary to previous research, these results indicate that positive and negative affect do not necessarily exert symmetrical effects on decision making. Implications for the major accounts of the influence of affect on decision making are discussed in relation to the findings.

Inhibition of forkhead boxO-specific transcription prevents mechanical ventilation-induced diaphragm dysfunction.

PubMed

Smuder, Ashley J; Sollanek, Kurt J; Min, Kisuk; Nelson, W Bradley; Powers, Scott K

2015-05-01

Mechanical ventilation is a lifesaving measure for patients with respiratory failure. However, prolonged mechanical ventilation results in diaphragm weakness, which contributes to problems in weaning from the ventilator. Therefore, identifying the signaling pathways responsible for mechanical ventilation-induced diaphragm weakness is essential to developing effective countermeasures to combat this important problem. In this regard, the forkhead boxO family of transcription factors is activated in the diaphragm during mechanical ventilation, and forkhead boxO-specific transcription can lead to enhanced proteolysis and muscle protein breakdown. Currently, the role that forkhead boxO activation plays in the development of mechanical ventilation-induced diaphragm weakness remains unknown. This study tested the hypothesis that mechanical ventilation-induced increases in forkhead boxO signaling contribute to ventilator-induced diaphragm weakness. University research laboratory. Young adult female Sprague-Dawley rats. Cause and effect was determined by inhibiting the activation of forkhead boxO in the rat diaphragm through the use of a dominant-negative forkhead boxO adeno-associated virus vector delivered directly to the diaphragm. Our results demonstrate that prolonged (12 hr) mechanical ventilation results in a significant decrease in both diaphragm muscle fiber size and diaphragm-specific force production. However, mechanically ventilated animals treated with dominant-negative forkhead boxO showed a significant attenuation of both diaphragm atrophy and contractile dysfunction. In addition, inhibiting forkhead boxO transcription attenuated the mechanical ventilation-induced activation of the ubiquitin-proteasome system, the autophagy/lysosomal system, and caspase-3. Forkhead boxO is necessary for the activation of key proteolytic systems essential for mechanical ventilation-induced diaphragm atrophy and contractile dysfunction. Collectively, these results suggest that targeting forkhead boxO transcription could be a key therapeutic target to combat ventilator-induced diaphragm dysfunction.

Dendritic cells with increased expression of suppressor of cytokine signaling 1(SOCS1) gene ameliorate lipopolysaccharide/d-galactosamine-induced acute liver failure.

PubMed

Li, Shan-Shan; Yang, Min; Chen, Yong-Ping; Tang, Xin-Yue; Zhang, Sheng-Guo; Ni, Shun-Lan; Yang, Nai-Bin; Lu, Ming-Qin

2018-05-28

Acute liver failure is a devastating clinical syndrome with extremely terrible inflammation reaction, which is still lack of effective treatment in clinic. Suppressor of Cytokine Signaling 1 protein is inducible intracellular negative regulator of Janus kinases (JAK)/signal transducers and activators of transcription (STAT) pathway that plays essential role in inhibiting excessive intracellular signaling cascade and preventing autoimmune reaction. In this paper, we want to explore whether dendritic cells (DCs) with overexpression of SOCS1 have a therapeutic effect on experimental acute liver failure. Bone marrow derived dendritic cells were transfected with lentivirus encoding SOCS1 and negative control lentivirus, thereafter collected for costimulatory molecules analysis, allogeneic Mixed Lymphocyte Reaction and Western blot test of JAK/STAT pathway. C57BL/6 mice were randomly separated into normal control and treatment groups which respectively received tail vein injection of modified DCs, negative control DCs and normal saline 12 h earlier than acute liver failure induction. Our results indicated that DCs with overexpression of SOCS1 exhibited like regulatory DCs (DCregs) with low level of costimulatory molecules and poor allostimulatory ability in vitro, which was supposed to correlate with block of JAK2/STAT1 signaling. In vivo tests, we found that infusion of modified DCs increased survival rate of acute liver failure mice and alleviate liver injury via inhibition of TLR4/HMGB1 pathway. We concluded that DCs transduced with SOCS1 gene exhibit as DCregs through negative regulation of JAK2/STAT1 pathway and ameliorated lipopolysaccharide/d-galactosamine induced acute liver failure via inhibition of TLR4 pathway. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of a glycine transporter-1 inhibitor and D-serine on MK-801-induced immobility in the forced swimming test in rats.

PubMed

Kawaura, Kazuaki; Koike, Hiroyuki; Kinoshita, Kohnosuke; Kambe, Daiji; Kaku, Ayaka; Karasawa, Jun-ichi; Chaki, Shigeyuki; Hikichi, Hirohiko

2015-02-01

Glutamatergic dysfunction, particularly the hypofunction of N-methyl-D-aspartate (NMDA) receptors, is involved in the pathophysiology of schizophrenia. The positive modulation of the glycine site on the NMDA receptor has been proposed as a novel therapeutic approach for schizophrenia. However, its efficacy against negative symptoms, which are poorly managed by current medications, has not been fully addressed. In the present study, the effects of the positive modulation of the glycine site on the NMDA receptor were investigated in an animal model of negative symptoms of schizophrenia. The subchronic administration of MK-801 increased immobility in the forced swimming test in rats without affecting spontaneous locomotor activity. The increased immobility induced by MK-801 was attenuated by the atypical antipsychotic clozapine but not by either the typical antipsychotic haloperidol or the antidepressant imipramine, indicating that the increased immobility induced by subchronic treatment with MK-801 in the forced swimming test may represent a negative symptom of schizophrenia. Likewise, positive modulation of the glycine sites on the NMDA receptor using an agonist for the glycine site, D-serine, and a glycine transporter-1 inhibitor, N-[(3R)-3-([1,1'-biphenyl]-4-yloxy)-3-(4-fluorophenyl)propyl]-N-methylglycine hydrochloride (NFPS), significantly reversed the increase in immobility in MK-801-treated rats without reducing the immobility time in vehicle-treated rats. The present results show that the stimulation of the NMDA receptor through the glycine site on the receptor either directly with D-serine or by blocking glycine transporter-1 attenuates the immobility elicited by the subchronic administration of MK-801 and may be potentially useful for the treatment of negative symptoms of schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Sphingosine mediates the immediate negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian cardiac myocyte.

PubMed

Oral, H; Dorn, G W; Mann, D L

1997-02-21

To determine whether activation of the neutral sphingomyelinase pathway was responsible for the immediate (<30 min) negative inotropic effects of tumor necrosis factor-alpha (TNF-alpha), we examined sphingosine levels in diluent and TNF-alpha-stimulated cardiac myocytes. TNF-alpha stimulation of adult feline cardiac myocytes provoked a rapid (<15 min) increase in the hydrolysis of [14C]sphingomyelin in cell-free extracts, as well as an increase in ceramide mass, consistent with cytokine-induced activation of the neutral sphingomyelinase pathway. High performance liquid chromatographic analysis of lipid extracts from TNF-alpha-stimulated cardiac myocytes showed that TNF-alpha stimulation produced a rapid (<30 min) increase in free sphingosine levels. Moreover, exogenous D-sphingosine mimicked the effects of TNF-alpha on intracellular calcium homeostasis, as well as the negative inotropic effects of TNF-alpha in isolated contracting myocytes; time course studies showed that exogenous D-sphingosine produced abnormalities in cell shortening that were maximal at 5 min. Finally, blocking sphingosine production using an inhibitor of ceramidase, n-oleoylethanolamine, completely abrogated the negative inotropic effects of TNF-alpha in isolated contracting cardiac myocytes. Additional studies employing biologically active ceramide analogs and sphingosine 1-phosphate suggested that neither the immediate precursor of sphingosine nor the immediate metabolite of sphingosine, respectively, were likely to be responsible for the immediate negative inotropic effects of TNF-alpha. Thus, these studies suggest that sphingosine mediates the immediate negative inotropic effects of TNF-alpha in isolated cardiac myocytes.

Phosphorylation of Trihelix Transcriptional Repressor ASR3 by MAP KINASE4 Negatively Regulates Arabidopsis Immunity

PubMed Central

Li, Bo; Jiang, Shan; Yu, Xiao; Cheng, Cheng; Chen, Sixue; Cheng, Yanbing; Yuan, Joshua S.; Jiang, Daohong; He, Ping; Shan, Libo

2015-01-01

Proper control of immune-related gene expression is crucial for the host to launch an effective defense response. Perception of microbe-associated molecular patterns (MAMPs) induces rapid and profound transcriptional reprogramming via unclear mechanisms. Here, we show that ASR3 (ARABIDOPSIS SH4-RELATED3) functions as a transcriptional repressor and plays a negative role in regulating pattern-triggered immunity (PTI) in Arabidopsis thaliana. ASR3 belongs to a plant-specific trihelix transcription factor family for which functional studies are lacking. MAMP treatments induce rapid phosphorylation of ASR3 at threonine 189 via MPK4, a mitogen-activated protein kinase that negatively regulates PTI responses downstream of multiple MAMP receptors. ASR3 possesses transcriptional repressor activity via its ERF-associated amphiphilic repression motifs and negatively regulates a large subset of flg22-induced genes. Phosphorylation of ASR3 by MPK4 enhances its DNA binding activity to suppress gene expression. Importantly, the asr3 mutant shows enhanced disease resistance to virulent bacterial pathogen infection, whereas transgenic plants overexpressing the wild-type or phospho-mimetic form of ASR3 exhibit compromised PTI responses. Our studies reveal a function of the trihelix transcription factors in plant innate immunity and provide evidence that ASR3 functions as a transcriptional repressor regulated by MAMP-activated MPK4 to fine-tune plant immune gene expression. PMID:25770109

The effects of antiepileptic inducers in neuropsychopharmacology, a neglected issue. Part I: A summary of the current state for clinicians.

PubMed

de Leon, Jose

2015-01-01

The literature on inducers in epilepsy and bipolar disorder is seriously contaminated by false negative findings. This is part i of a comprehensive review on antiepileptic drug (AED) inducers using both mechanistic pharmacological and evidence-based medicine to provide practical recommendations to neurologists and psychiatrists concerning how to control for them. Carbamazepine, phenobarbital and phenytoin, are clinically relevant AED inducers; correction factors were calculated for studied induced drugs. These correction factors are rough simplifications for orienting clinicians, since there is great variability in the population regarding inductive effects. As new information is published, the correction factors may need to be modified. Some of the correction factors are so high that the drugs (e.g., bupropion, quetiapine or lurasidone) should not co-prescribed with potent inducers. Clobazam, eslicarbazepine, felbamate, lamotrigine, oxcarbazepine, rufinamide, topiramate, vigabatrin and valproic acid are grouped as mild inducers which may (i)be inducers only in high doses; (ii)frequently combine with inhibitory properties; and (iii)take months to reach maximum effects or de-induction, definitively longer than the potent inducers. Potent inducers, definitively, and mild inducers, possibly, have relevant effects in the endogenous metabolism of (i)sexual hormones, (ii) vitamin D, (iii)thyroid hormones, (iv)lipid metabolism, and (v)folic acid. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer.

PubMed

King, Suzanne N; Dunlap, Neal E; Tennant, Paul A; Pitts, Teresa

2016-06-01

Oncologic treatments, such as curative radiotherapy and chemoradiation, for head and neck cancer can cause long-term swallowing impairments (dysphagia) that negatively impact quality of life. Radiation-induced dysphagia comprised a broad spectrum of structural, mechanical, and neurologic deficits. An understanding of the biomolecular effects of radiation on the time course of wound healing and underlying morphological tissue responses that precede radiation damage will improve options available for dysphagia treatment. The goal of this review is to discuss the pathophysiology of radiation-induced injury and elucidate areas that need further exploration.

An Anionic Phospholipid Enables the Hydrophobic Surfactant Proteins to Alter Spontaneous Curvature

PubMed Central

Chavarha, Mariya; Loney, Ryan W.; Rananavare, Shankar B.; Hall, Stephen B.

2013-01-01

The hydrophobic surfactant proteins, SP-B and SP-C, greatly accelerate the adsorption of the surfactant lipids to an air/water interface. Previous studies of factors that affect curvature suggest that vesicles may adsorb via a rate-limiting structure with prominent negative curvature, in which the hydrophilic face of the lipid leaflets is concave. To determine if SP-B and SP-C might promote adsorption by inducing negative curvature, we used small-angle x-ray scattering to test whether the physiological mixture of the two proteins affects the radius of cylindrical monolayers in the inverse hexagonal phase. With dioleoyl phosphatidylethanolamine alone, the proteins had no effect on the hexagonal lattice constant, suggesting that the proteins fail to insert into the cylindrical monolayers. The surfactant lipids also contain ∼10% anionic phospholipids, which might allow incorporation of the cationic proteins. With 10% of the anionic dioleoyl phosphatidylglycerol added to dioleoyl phosphatidylethanolamine, the proteins induced a dose-related decrease in the hexagonal lattice constant. At 30°C, the reduction reached a maximum of 8% relative to the lipids alone at ∼1% (w/w) protein. Variation of NaCl concentration tested whether the effect of the protein represented a strictly electrostatic effect that screening by electrolyte would eliminate. With concentrations up to 3 M NaCl, the dose-related change in the hexagonal lattice constant decreased but persisted. Measurements at different hydrations determined the location of the pivotal plane and proved that the change in the lattice constant produced by the proteins resulted from a shift in spontaneous curvature. These results provide the most direct evidence yet that the surfactant proteins can induce negative curvature in lipid leaflets. This finding supports the model in which the proteins promote adsorption by facilitating the formation of a negatively curved, rate-limiting structure. PMID:23442910

Local versus systemic effect of ovulation-inducing factor in the seminal plasma of alpacas

PubMed Central

Ratto, Marcelo H; Huanca, Wilfredo; Singh, Jaswant; Adams, Gregg P

2005-01-01

Background Camelids are induced (reflex) ovulators. We have recently documented the presence of an ovulation-inducing factor (OIF) in the seminal plasma of alpacas and llamas. The objective was to test the hypothesis that OIF exerts its effect via a systemic rather than a local route and that endometrial curettage will enhance the ovulatory response to intrauterine deposition of seminal plasma in alpacas. Methods Female alpacas were assigned randomly to 6 groups (n = 15 to 17 per group) in a 2 × 3 factorial design to test the effect of seminal plasma versus phosphate-buffered saline (PBS) given by intramuscular injection, by intrauterine infusion, or by intrauterine infusion after endometrial curettage. Specifically, alpacas in the respective groups were given 1) 2 ml of alpaca seminal plasma intramuscularly, 2) 2 ml of PBS intramuscularly (negative control group), 3) 2 ml of alpaca seminal plasma by intrauterine infusion, 4) 2 ml of PBS by intrauterine infusion (negative control group), 5) 2 ml of alpaca seminal plasma by intrauterine infusion after endometrial curettage, or 6) 2 ml of PBS by intrauterine infusion after endometrial curettage (negative control group). The alpacas were examined by transrectal ultrasonography to detect ovulation and measure follicular and luteal diameters. Results Intramuscular administration of seminal plasma resulted in a higher ovulation rate than intrauterine administration of seminal plasma (93% versus 41%; P < 0.01), while intrauterine seminal plasma after endometrial curettage was intermediate (67%). None of the saline-treated controls ovulated. The diameter of the CL after treatment-induced ovulation was not affected by the route of administration of seminal plasma. Conclusion We conclude that 1) OIF in seminal plasma effects ovulation via a systemic rather than a local route, 2) disruption of the endometrial mucosa by curettage facilitated the absorption of OIF and increased the ovulatory effect of seminal plasma, and 3) ovulation in alpacas is not associated with a physical stimulation of the genital tract, and 4) the alpaca represents an excellent biological model to evaluate the bioactivity of OIF. PMID:16018817

How does social support relieve depression among flood victims? The contribution of feelings of safety, self-disclosure, and negative cognition.

PubMed

Zhen, Rui; Quan, Lijuan; Zhou, Xiao

2018-03-15

Depression is one of the most common post-trauma symptoms that can be alleivated by social support. The purpose of this study was to examine the multiple mediating effects of social support on depression via feelings of safety, disclosure, and negative cognition. One hundred and eighty-seven flood victims in Wuhu City, an area affected most severely by a flood during July 2016, were selected to complete a self-report questionnaire package. Social support has four indirect negative effects on depression, including a one-step indirect path to self-disclosure, 2 two-step paths from feelings of safety to self-disclosure, and from self-disclosure to negative cognition about self, and a three-step indirect path from feelings of life safety via self-disclosure to negative self-cognition. All variables were measured using self-report scales. Social support may relieve depression in flood victims by inducing feelings of safety and self-disclosure, and by relieving negative cognition. Copyright © 2018 Elsevier B.V. All rights reserved.

False-negative dipyridamole-thallium-201 myocardial imaging after caffeine infusion

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

Smits, P.; Corstens, F.H.; Aengevaeren, W.R.

1991-08-01

The vasodilator effect of intravenously administered dipyridamole may be caused by an increase in endogenous plasma adenosine levels. The authors evaluated the effect of caffeine, an adenosine receptor antagonist, on the diagnostic results of dipyridamole-201Tl myocardial imaging in eight patients with coronary artery disease. Caffeine infusion significantly attenuated the dipyridamole-induced fall in blood pressure and the accompanied increase in heart rate. The infusion of dipyridamole alone resulted in chest pain and ST-segment depressions on the electrocardiogram in four patients, whereas none of these problems occurred when the tests were repeated after caffeine. In six of eight patients, caffeine was responsiblemore » for false-negative dipyridamole-201Tl tests. Semiquantitive scores of the dipyridamole-induced 201Tl perfusion defects were decreased by caffeine from 9.0 {plus minus} 0.9 to 2.0 {plus minus} 1.1 points (p less than 0.05). Computerized analysis revealed a caffeine-mediated reduction in the percent reversibility of the images from 46% {plus minus} 16% to 6% {plus minus} 10% (p less than 0.05). They conclude that the use of caffeinated products prior to dipyridamole-201Tl testing may be responsible for false-negative findings.« less

Exercise program-induced mood improvement and improved eating in severely obese adults.

PubMed

Annesi, James J; Tennant, Gisèle A

Using a practical setting, this study aimed to test exercise and nutrition interventions' effects on negative mood, self-regulation, and self-efficacy to control eating; and to assess the ability of mood change to predict changes in eating behavior, while accounting for changes in self-regulation and self-efficacy. Severely obese adults participated in a cognitive-behavioral exercise support treatment paired with either nutrition education (n = 140) or cognitive-behavioral methods applied to improved eating (n = 146). They were assessed on measures of overall negative mood, self-regulatory skill usage, self-efficacy to control eating when negative moods are present, and fruit and vegetable consumption at baseline and Week 26. Significant improvements in each psychosocial variable and fruit and vegetable intake were found. Improved mood significantly predicted fruit and vegetable consumption change, R2 = 0.12, P < 0.001. Entry of changes in self-regulation and self-efficacy into the multiple regression equation significantly strengthened the variance explained, R2 = 0.18, P < 0.001. Findings suggest that exercise-induced improvements in mood improve eating behaviors, with increases in self-regulation and self-efficacy adding to this effect.

Identification of Breast Cancer Inhibitors Specific for G Protein-Coupled Estrogen Receptor (GPER)-Expressing Cells.

PubMed

Aiello, Francesca; Carullo, Gabriele; Giordano, Francesca; Spina, Elena; Nigro, Alessandra; Garofalo, Antonio; Tassini, Sabrina; Costantino, Gabriele; Vincetti, Paolo; Bruno, Agostino; Radi, Marco

2017-08-22

Together with estrogen receptors ERα and ERβ, the G protein-coupled estrogen receptor (GPER) mediates important pathophysiological signaling pathways induced by estrogens and is currently regarded as a promising target for ER-negative (ER-) and triple-negative (TN) breast cancer. Only a few selective GPER modulators have been reported to date, and their use in cancer cell lines has often led to contradictory results. Herein we report the application of virtual screening and cell-based studies for the identification of new chemical scaffolds with a specific antiproliferative effect against GPER-expressing breast cancer cell lines. Out of the four different scaffolds identified, 8-chloro-4-(4-chlorophenyl)pyrrolo[1,2-a]quinoxaline 14 c was found to be the most promising compound able to induce: 1) antiproliferative activity in GPER-expressing cell lines (MCF7 and SKBR3), similarly to G15; 2) no effect on cells that do not express GPER (HEK293); 3) a decrease in cyclin D1 expression; and 4) a sustained induction of cell-cycle negative regulators p53 and p21. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Positive and negative modulation of circadian activity rhythms by mGluR5 and mGluR2/3 metabotropic glutamate receptors.

PubMed

Gannon, Robert L; Millan, Mark J

2011-01-01

Glutamate released from retinal ganglion cells conveys information about the daily light:dark cycle to master circadian pacemaker neurons within the suprachiasmatic nucleus that then synchronize internal circadian rhythms with the external day-length. Glutamate activation of ionotropic glutamate receptors in the suprachiasmatic nucleus is well established, but the function of the metabotropic glutamate receptors that are also located in this nucleus is not known. Therefore, in this study we evaluated agonists and antagonists acting at orthosteric or allosteric sites for mGluR5 and mGluR2/3 metabotropic glutamate receptors for their ability to modulate light-induced phase advances and delays of hamster circadian activity rhythms. mGluR5 allosteric antagonists fenobam, MPEP and MTEP, each 10 mg/kg, potentiated light-induced phase advances of hamster circadian activity rhythms, while the mGluR5 agonists CHPG, (S)-3,5-DHPG or positive allosteric modulator CDPPB had no effect. Neither mGluR5 agonists nor antagonists had any effect on light-induced phase delays of activity rhythms. The competitive mGluR2/3 antagonist LY341495, 10 mg/kg, also potentiated light-induced phase advances, but inhibited light-induced phase delays. The mGluR2/3 agonists LY354740 and LY404039 were without effect on phase advances while a third agonist LY379268, 10 mg/kg, inhibited both light-induced advances and delays. Finally, mGluR2/3 agonists LY379268 and LY404039 also inhibited light-induced phase delays of activity rhythms. These results suggest that during light-induced phase advances, mGluR2/3 and mGluR5 receptors act to negatively modulate the effects of light on the circadian pacemaker or its output(s). mGluR5 receptors do not appear to be involved during light-induced phase delays. In contrast, the role for mGluR2/3 receptors during phase delays is more complicated as both agonists and antagonists inhibit light-induced phase delays. Dysfunctions in human circadian rhythms have been implicated in some forms of depression, and metabotropic glutamate receptor ligands, which are also being evaluated for antidepressant activity, are shown here to be capable of modifying light-induced phase shifts of circadian activity rhythms. Copyright © 2010 Elsevier Ltd. All rights reserved.

Prevention of chemotherapy-induced alopecia in rodent models

PubMed Central

Jimenez, Joaquin J.; Roberts, Stephen M.; Mejia, Jessica; Mauro, Lucia M.; Munson, John W.; Elgart, George W.; Connelly, Elizabeth Alvarez; Chen, Qingbin; Zou, Jiangying; Goldenberg, Carlos

2008-01-01

Alopecia (hair loss) is experienced by thousands of cancer patients every year. Substantial-to-severe alopecia is induced by anthracyclines (e.g., adriamycin), taxanes (e.g., taxol), alkylating compounds (e.g., cyclophosphamide), and the topisomerase inhibitor etoposide, agents that are widely used in the treatment of leukemias and breast, lung, ovarian, and bladder cancers. Currently, no treatment appears to be generally effective in reliably preventing this secondary effect of chemotherapy. We observed in experiments using different rodent models that localized administration of heat or subcutaneous/intradermal injection of geldanamycin or 17-(allylamino)-17-demethoxygeldanamycin induced a stress protein response in hair follicles and effectively prevented alopecia from adriamycin, cyclophosphamide, taxol, and etoposide. Model tumor therapy experiments support the presumption that such localized hair-saving treatment does not negatively affect chemotherapy efficacy. PMID:18347939

Measurements of the Time-Averaged and Instantaneous Induced Velocities in the Wake of a Helicopter Rotor Hovering at High Tip Speeds

NASA Technical Reports Server (NTRS)

Heyson, Harry H.

1960-01-01

Measurements of the time-averaged induced velocities were obtained for rotor tip speeds as great as 1,100 feet per second (tip Mach number of 0.98) and measurements of the instantaneous induced velocities were obtained for rotor tip speeds as great as 900 feet per second. The results indicate that the small effects on the wake with increasing Mach number are primarily due to the changes in rotor-load distribution resulting from changes in Mach number rather than to compressibility effects on the wake itself. No effect of tip Mach number on the instantaneous velocities was observed. Under conditions for which the blade tip was operated at negative pitch angles, an erratic circulatory flow was observed.

Add-on effects of a low-dose aripiprazole in resolving hyperprolactinemia induced by risperidone or paliperidone.

PubMed

Qiao, Ying; Yang, Fuzhong; Li, Chunbo; Guo, Qian; Wen, Hui; Zhu, Suoyu; Ouyang, Qiong; Shen, Weidi; Sheng, Jianhua

2016-03-30

This study investigated the effects of a low-dose aripiprazole adjunctive treatment for risperidone- or paliperidone-induced hyperprolactinemia in Han Chinese women with schizophrenia. After 4 weeks of risperidone or paliperidone treatment, 60 out of 66 patients improved significantly and experienced hyperprolactinemia. They were randomly assigned to the treatment group (aripiprazole adjunctive treatment) (n=30) or control group (non-adjunctive treatment) (n=30). The dosage of risperidone and paliperidone were maintained; and aripiprazole was maintained at 5mg/day during the 8-week study period. The prolactin levels at the end of the 8th week were significantly lower in the treatment group than in the control group. The estradiol level correlated negatively with serum prolactin level both in the treatment group and the control group at the end of the 8th week and the 4th week respectively. The Positive and Negative Syndrome Scale score improved significantly during the 8-week study period in both groups. The incidence of treatment-emergent adverse event was similar in two groups. Low-dose aripiprazole adjunctive treatment is effective in relieving risperidone- and paliperidone-induced hyperprolactinemia in female schizophrenic patients without increasing adverse event. Copyright © 2016. Published by Elsevier Ireland Ltd.

Membrane Permeabilization Induced by Sphingosine: Effect of Negatively Charged Lipids

PubMed Central

Jiménez-Rojo, Noemi; Sot, Jesús; Viguera, Ana R.; Collado, M. Isabel; Torrecillas, Alejandro; Gómez-Fernández, J.C.; Goñi, Félix M.; Alonso, Alicia

2014-01-01

Sphingosine [(2S, 3R, 4E)-2-amino-4-octadecen-1, 3-diol] is the most common sphingoid long chain base in sphingolipids. It is the precursor of important cell signaling molecules, such as ceramides. In the last decade it has been shown to act itself as a potent metabolic signaling molecule, by activating a number of protein kinases. Moreover, sphingosine has been found to permeabilize phospholipid bilayers, giving rise to vesicle leakage. The present contribution intends to analyze the mechanism by which this bioactive lipid induces vesicle contents release, and the effect of negatively charged bilayers in the release process. Fluorescence lifetime measurements and confocal fluorescence microscopy have been applied to observe the mechanism of sphingosine efflux from large and giant unilamellar vesicles; a graded-release efflux has been detected. Additionally, stopped-flow measurements have shown that the rate of vesicle permeabilization increases with sphingosine concentration. Because at the physiological pH sphingosine has a net positive charge, its interaction with negatively charged phospholipids (e.g., bilayers containing phosphatidic acid together with sphingomyelins, phosphatidylethanolamine, and cholesterol) gives rise to a release of vesicular contents, faster than with electrically neutral bilayers. Furthermore, phosphorous 31-NMR and x-ray data show the capacity of sphingosine to facilitate the formation of nonbilayer (cubic phase) intermediates in negatively charged membranes. The data might explain the pathogenesis of Niemann-Pick type C1 disease. PMID:24940775

Sweet Chestnut (Castanea sativa Mill.) Bark Extract: Cardiovascular Activity and Myocyte Protection against Oxidative Damage

PubMed Central

Chiarini, Alberto; Micucci, Matteo; Ioan, Pierfranco; Fimognari, Carmela; Gallina Toschi, Tullia; Comandini, Patrizia; Hrelia, Silvana

2013-01-01

This work was aimed at evaluating the cardioprotective effects of Castanea sativa Mill. (CSM) bark extract characterized in its phenolic composition by HPLC-DAD-MS analysis. The study was performed using primary cultures of neonatal rat cardiomyocytes to investigate the antioxidant and cytoprotective effects of CSM bark extract and isolated guinea pig left and right atria, left papillary muscle, and aorta to evaluate its direct effect on cholinergic and adrenergic response. In cultured cardiomyocytes the CSM bark extract reduced intracellular reactive oxygen species formation and improved cell viability following oxidative stress in dose-dependent manner. Moreover, the extract decreased the contraction induced by noradrenaline (1 μM) in guinea pig aortic strips and induced transient negative chronotropic and positive inotropic effects without involvement of cholinergic or adrenergic receptors in the guinea pig atria. Our results indicate that CSM bark extract exhibits antioxidant activity and might induce cardioprotective effect. PMID:23533692

Discrepancy and Disliking Do Not Induce Negative Opinion Shifts

PubMed Central

Flache, Andreas; Mäs, Michael

2016-01-01

Both classical social psychological theories and recent formal models of opinion differentiation and bi-polarization assign a prominent role to negative social influence. Negative influence is defined as shifts away from the opinion of others and hypothesized to be induced by discrepancy with or disliking of the source of influence. There is strong empirical support for the presence of positive social influence (a shift towards the opinion of others), but evidence that large opinion differences or disliking could trigger negative shifts is mixed. We examine positive and negative influence with controlled exposure to opinions of other individuals in one experiment and with opinion exchange in another study. Results confirm that similarities induce attraction, but results do not support that discrepancy or disliking entails negative influence. Instead, our findings suggest a robust positive linear relationship between opinion distance and opinion shifts. PMID:27333160

Diabetes-induced hepatic pathogenic damage, inflammation, oxidative stress, and insulin resistance was exacerbated in zinc deficient mouse model.

PubMed

Zhang, Chi; Lu, Xuemian; Tan, Yi; Li, Bing; Miao, Xiao; Jin, Litai; Shi, Xue; Zhang, Xiang; Miao, Lining; Li, Xiaokun; Cai, Lu

2012-01-01

Zinc (Zn) deficiency often occurs in the patients with diabetes. Effects of Zn deficiency on diabetes-induced hepatic injury were investigated. Type 1 diabetes was induced in FVB mice with multiple low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with and without Zn chelator, N,N,N',N'-tetrakis (2-pyridylemethyl) ethylenediamine (TPEN), at 5 mg/kg body-weight daily for 4 months. Hepatic injury was examined by serum alanine aminotransferase (ALT) level and liver histopathological and biochemical changes. Hepatic Zn deficiency (lower than control level, p<0.05) was seen in the mice with either diabetes or TPEN treatment and more evident in the mice with both diabetes and TPEN. Zn deficiency exacerbated hepatic injuries, shown by further increased serum ALT, hepatic lipid accumulation, inflammation, oxidative damage, and endoplasmic reticulum stress-related cell death in Diabetes/TPEN group compared to Diabetes alone. Diabetes/TPEN group also showed a significant decrease in nuclear factor-erythroid 2-related factor 2 (Nrf2) expression and transcription action along with significant increases in Akt negative regulators, decrease in Akt and GSK-3β phosphorylation, and increase in nuclear accumulation of Fyn (a Nrf2 negative regulator). In vitro study with HepG2 cells showed that apoptotic effect of TPEN at 0.5-1.0 µM could be completely prevented by simultaneous Zn supplementation at the dose range of 30-50 µM. Zn is required for maintaining Akt activation by inhibiting the expression of Akt negative regulators; Akt activation can inhibit Fyn nuclear translocation to export nuclear Nrf2 to cytoplasm for degradation. Zn deficiency significantly enhanced diabetes-induced hepatic injury likely through down-regulation of Nrf2 function.

Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism.

PubMed

Wolfson, Manuel Luis; Schander, Julieta Aylen; Bariani, María Victoria; Correa, Fernando; Franchi, Ana María

2015-12-15

Genital tract infections caused by Gram-negative bacteria induce miscarriage and are one of the most common complications of human pregnancy. LPS administration to 7-day pregnant mice induces embryo resorption after 24h, with nitric oxide playing a fundamental role in this process. We have previously shown that progesterone exerts protective effects on the embryo by modulating the inflammatory reaction triggered by LPS. Here we sought to investigate whether the in vivo administration of progesterone modulated the LPS-induced nitric oxide production from peripheral blood mononuclear cells from pregnant and non-pregnant mice. We found that progesterone downregulated LPS-induced nitric oxide production by a progesterone receptor-independent mechanism. Moreover, our results suggest a possible participation of glucocorticoid receptors in at least some of the anti-inflammatory effects of progesterone. Copyright © 2015 Elsevier B.V. All rights reserved.

Depressive mood ratings are reduced by MDMA in female polydrug ecstasy users homozygous for the l-allele of the serotonin transporter.

PubMed

Kuypers, K P C; de la Torre, R; Farre, M; Xicota, L; de Sousa Fernandes Perna, E B; Theunissen, E L; Ramaekers, J G

2018-01-18

MDMA exerts its main effects via the serotonergic system and the serotonin transporter. The gene coding for this transporter determines the expression rate of the transporter. Previously it was shown that healthy individuals with the short allelic variant ('s-group') of the 5-HTTLPR-polymorphism displayed more anxiety and negative mood, and had a lower transcriptional efficiency compared to individuals who are homozygous for the l-allele ('l-group'). The present study aimed to investigate the role of the 5-HTTLPR polymorphism in MDMA-induced mood effects. Four placebo-controlled, within-subject studies were pooled, including in total 63 polydrug ecstasy users (N s-group  = 48; N l-group  = 15) receiving MDMA 75 mg and placebo on two test days, separated by minimally 7 days. Mood was assessed by means of the Profile of Mood States. Findings showed that MDMA induced -independent of sex- a positive mood state, and as a side effect also increased two negative affect states, anxiety and confusion. Anxiety ratings were higher in the l-group and independent of treatment or sex. Depression ratings were lowered by MDMA in the female l-group. Findings indicate that the MDMA-induced reduction in self-rated depressive feelings is sex- and genotype-dependent, with females homozygous for the l-allele showing this beneficial effect.

Effects of CO2-induced pH reduction on the exoskeleton structure and biophotonic properties of the shrimp Lysmata californica

PubMed Central

Taylor, Jennifer R. A.; Gilleard, Jasmine M.; Allen, Michael C.; Deheyn, Dimitri D.

2015-01-01

The anticipated effects of CO2-induced ocean acidification on marine calcifiers are generally negative, and include dissolution of calcified elements and reduced calcification rates. Such negative effects are not typical of crustaceans for which comparatively little ocean acidification research has been conducted. Crustaceans, however, depend on their calcified exoskeleton for many critical functions. Here, we conducted a short-term study on a common caridean shrimp, Lysmata californica, to determine the effect of CO2-driven reduction in seawater pH on exoskeleton growth, structure, and mineralization and animal cryptic coloration. Shrimp exposed to ambient (7.99 ± 0.04) and reduced pH (7.53 ± 0.06) for 21 days showed no differences in exoskeleton growth (percent increase in carapace length), but the calcium weight percent of their cuticle increased significantly in reduced pH conditions, resulting in a greater Ca:Mg ratio. Cuticle thickness did not change, indicating an increase in the mineral to matrix ratio, which may have mechanical consequences for exoskeleton function. Furthermore, there was a 5-fold decrease in animal transparency, but no change in overall shrimp coloration (red). These results suggest that even short-term exposure to CO2-induced pH reduction can significantly affect exoskeleton mineralization and shrimp biophotonics, with potential impacts on crypsis, physical defense, and predator avoidance. PMID:26030212

Elevated [CO2] does not ameliorate the negative effects of elevated temperature on drought-induced mortality in Eucalyptus radiata seedlings.

PubMed

Duan, Honglang; Duursma, Remko A; Huang, Guomin; Smith, Renee A; Choat, Brendan; O'Grady, Anthony P; Tissue, David T

2014-07-01

It has been reported that elevated temperature accelerates the time-to-mortality in plants exposed to prolonged drought, while elevated [CO(2)] acts as a mitigating factor because it can reduce stomatal conductance and thereby reduce water loss. We examined the interactive effects of elevated [CO(2)] and temperature on the inter-dependent carbon and hydraulic characteristics associated with drought-induced mortality in Eucalyptus radiata seedlings grown in two [CO(2)] (400 and 640 μL L(-1)) and two temperature (ambient and ambient +4 °C) treatments. Seedlings were exposed to two controlled drying and rewatering cycles, and then water was withheld until plants died. The extent of xylem cavitation was assessed as loss of stem hydraulic conductivity. Elevated temperature triggered more rapid mortality than ambient temperature through hydraulic failure, and was associated with larger water use, increased drought sensitivities of gas exchange traits and earlier occurrence of xylem cavitation. Elevated [CO(2)] had a negligible effect on seedling response to drought, and did not ameliorate the negative effects of elevated temperature on drought. Our findings suggest that elevated temperature and consequent higher vapour pressure deficit, but not elevated [CO(2)], may be the primary contributors to drought-induced seedling mortality under future climates. © 2013 John Wiley & Sons Ltd.

Effects of CO2-induced pH reduction on the exoskeleton structure and biophotonic properties of the shrimp Lysmata californica.

PubMed

Taylor, Jennifer R A; Gilleard, Jasmine M; Allen, Michael C; Deheyn, Dimitri D

2015-06-01

The anticipated effects of CO2-induced ocean acidification on marine calcifiers are generally negative, and include dissolution of calcified elements and reduced calcification rates. Such negative effects are not typical of crustaceans for which comparatively little ocean acidification research has been conducted. Crustaceans, however, depend on their calcified exoskeleton for many critical functions. Here, we conducted a short-term study on a common caridean shrimp, Lysmata californica, to determine the effect of CO2-driven reduction in seawater pH on exoskeleton growth, structure, and mineralization and animal cryptic coloration. Shrimp exposed to ambient (7.99 ± 0.04) and reduced pH (7.53 ± 0.06) for 21 days showed no differences in exoskeleton growth (percent increase in carapace length), but the calcium weight percent of their cuticle increased significantly in reduced pH conditions, resulting in a greater Ca:Mg ratio. Cuticle thickness did not change, indicating an increase in the mineral to matrix ratio, which may have mechanical consequences for exoskeleton function. Furthermore, there was a 5-fold decrease in animal transparency, but no change in overall shrimp coloration (red). These results suggest that even short-term exposure to CO2-induced pH reduction can significantly affect exoskeleton mineralization and shrimp biophotonics, with potential impacts on crypsis, physical defense, and predator avoidance.

Beneficial effects of paeoniflorin on osteoporosis induced by high-carbohydrate, high-fat diet-associated hyperlipidemia in vivo.

PubMed

Wang, Yanmao; Zhu, Yu; Lu, Shengdi; Hu, Chengfang; Zhong, Wanrun; Chai, Yimin

2018-04-15

Osteoporosis is linked to reduced bone mineral density (BMD) as a major risk factor for fragility fractures. Recent studies indicated an association between BMD and abnormally elevated lipid levels in blood as common indicators for hyperlipidemia. In this study, we assessed the protective effect of paeoniflorin, a phytochemical compound with multiple pharmacological activities, against hyperlipidemia-induced osteoporosis in rats fed a high-carbohydrate, high-fat diet (HCHF). The special diet-fed rats were subjected to an 8-week treatment with either paeoniflorin (20 mg/kg, daily) or vehicle. The control group received a normal diet during the entire study. At study conclusion, serum markers of lipid metabolism and bone turnover were measured. Bone strength was assessed by biomechanical testing, and femurs were scanned using micro-computed tomography to analyze trabecular and cortical bone structure. Interestingly, paeoniflorin controlled the serum lipid profile by significantly decreasing HCHF-induced high levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol. Paeoniflorin significantly improved trabecular and cortical parameters as well as femur length and width that were negatively affected by HCHF diet. Biomechanical strength testing showed that femurs of HCHF diet-fed rats endured significantly lower force but higher displacement and strain than those of control rats, whereas paeoniflorin reversed the negative effects. Moreover, paeoniflorin rescued osteoblast differentiation and cell spreading activities along with bone turnover markers. In conclusion, HCHF-induced hyperlipidemia caused adverse effects on the bone that were rescued by paeoniflorin treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

The effect of mood on false memory for emotional DRM word lists.

PubMed

Zhang, Weiwei; Gross, Julien; Hayne, Harlene

2017-04-01

In the present study, we investigated the effect of participants' mood on true and false memories of emotional word lists in the Deese-Roediger-McDermott (DRM) paradigm. In Experiment 1, we constructed DRM word lists in which all the studied words and corresponding critical lures reflected a specified emotional valence. In Experiment 2, we used these lists to assess mood-congruent true and false memory. Participants were randomly assigned to one of three induced-mood conditions (positive, negative, or neutral) and were presented with word lists comprised of positive, negative, or neutral words. For both true and false memory, there was a mood-congruent effect in the negative mood condition; this effect was due to a decrease in true and false recognition of the positive and neutral words. These findings are consistent with both spreading-activation and fuzzy-trace theories of DRM performance and have practical implications for our understanding of the effect of mood on memory.

ONC201 activates ER stress to inhibit the growth of triple-negative breast cancer cells

PubMed Central

Yuan, Xun; Kho, Dhonghyo; Xu, Jing; Gajan, Ambikai; Wu, Kongming; Wu, Gen Sheng

2017-01-01

ONC201 was previously identified as a first-in-class antitumor agent and small-molecule inducer of the TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) gene that induces apoptosis in cancer cells. ONC201 has a safety profile and is currently in phase II clinical trials for the treatment of various malignancies. In the current study, we examine the effect of ONC201 on triple-negative breast cancer cells (TNBC), a subtype of breast cancer that is sensitive to TRAIL. We find that ONC201 inhibits the growth of TNBC cells including TNBC cells that have developed acquired TRAIL resistance. However, TNBC cells that have developed acquired ONC201 resistance are cross-resistant to TRAIL. Mechanistically, ONC201 triggers an integrated stress response (ISR) involving the activation of the transcription factor ATF4. Knockdown of ATF4 impairs ONC201-induced apoptosis of TNBC cells. Importantly, the activation of ATF4 is compromised in ONC201-resistant TNBC cells. Thus, our results indicate that ONC201 induces an ISR to cause TNBC cell death and suggest that TNBC patients may benefit from ONC201-based therapies. PMID:28423492

ONC201 activates ER stress to inhibit the growth of triple-negative breast cancer cells.

PubMed

Yuan, Xun; Kho, Dhonghyo; Xu, Jing; Gajan, Ambikai; Wu, Kongming; Wu, Gen Sheng

2017-03-28

ONC201 was previously identified as a first-in-class antitumor agent and small-molecule inducer of the TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) gene that induces apoptosis in cancer cells. ONC201 has a safety profile and is currently in phase II clinical trials for the treatment of various malignancies. In the current study, we examine the effect of ONC201 on triple-negative breast cancer cells (TNBC), a subtype of breast cancer that is sensitive to TRAIL. We find that ONC201 inhibits the growth of TNBC cells including TNBC cells that have developed acquired TRAIL resistance. However, TNBC cells that have developed acquired ONC201 resistance are cross-resistant to TRAIL. Mechanistically, ONC201 triggers an integrated stress response (ISR) involving the activation of the transcription factor ATF4. Knockdown of ATF4 impairs ONC201-induced apoptosis of TNBC cells. Importantly, the activation of ATF4 is compromised in ONC201-resistant TNBC cells. Thus, our results indicate that ONC201 induces an ISR to cause TNBC cell death and suggest that TNBC patients may benefit from ONC201-based therapies.

Brain signaling and behavioral responses induced by exposure to (56)Fe-particle radiation

NASA Technical Reports Server (NTRS)

Denisova, N. A.; Shukitt-Hale, B.; Rabin, B. M.; Joseph, J. A.

2002-01-01

Previous experiments have demonstrated that exposure to 56Fe-particle irradiation (1.5 Gy, 1 GeV) produced aging-like accelerations in neuronal and behavioral deficits. Astronauts on long-term space flights will be exposed to similar heavy-particle radiations that might have similar deleterious effects on neuronal signaling and cognitive behavior. Therefore, the present study evaluated whether radiation-induced spatial learning and memory behavioral deficits are associated with region-specific brain signaling deficits by measuring signaling molecules previously found to be essential for behavior [pre-synaptic vesicle proteins, synaptobrevin and synaptophysin, and protein kinases, calcium-dependent PRKCs (also known as PKCs) and PRKA (PRKA RIIbeta)]. The results demonstrated a significant radiation-induced increase in reference memory errors. The increases in reference memory errors were significantly negatively correlated with striatal synaptobrevin and frontal cortical synaptophysin expression. Both synaptophysin and synaptobrevin are synaptic vesicle proteins that are important in cognition. Striatal PRKA, a memory signaling molecule, was also significantly negatively correlated with reference memory errors. Overall, our findings suggest that radiation-induced pre-synaptic facilitation may contribute to some previously reported radiation-induced decrease in striatal dopamine release and for the disruption of the central dopaminergic system integrity and dopamine-mediated behavior.

Brain signaling and behavioral responses induced by exposure to (56)Fe-particle radiation.

PubMed

Denisova, N A; Shukitt-Hale, B; Rabin, B M; Joseph, J A

2002-12-01

Previous experiments have demonstrated that exposure to 56Fe-particle irradiation (1.5 Gy, 1 GeV) produced aging-like accelerations in neuronal and behavioral deficits. Astronauts on long-term space flights will be exposed to similar heavy-particle radiations that might have similar deleterious effects on neuronal signaling and cognitive behavior. Therefore, the present study evaluated whether radiation-induced spatial learning and memory behavioral deficits are associated with region-specific brain signaling deficits by measuring signaling molecules previously found to be essential for behavior [pre-synaptic vesicle proteins, synaptobrevin and synaptophysin, and protein kinases, calcium-dependent PRKCs (also known as PKCs) and PRKA (PRKA RIIbeta)]. The results demonstrated a significant radiation-induced increase in reference memory errors. The increases in reference memory errors were significantly negatively correlated with striatal synaptobrevin and frontal cortical synaptophysin expression. Both synaptophysin and synaptobrevin are synaptic vesicle proteins that are important in cognition. Striatal PRKA, a memory signaling molecule, was also significantly negatively correlated with reference memory errors. Overall, our findings suggest that radiation-induced pre-synaptic facilitation may contribute to some previously reported radiation-induced decrease in striatal dopamine release and for the disruption of the central dopaminergic system integrity and dopamine-mediated behavior.

Protective effects of piperine on lead acetate induced-nephrotoxicity in rats

PubMed Central

Sudjarwo, Sri Agus; Eraiko, Koerniasari; Sudjarwo, Giftania Wardani; Koerniasari

2017-01-01

Objective(s): In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue. Materials and Methods: Forty male rats were divided into 5 groups: negative control (rats were given aquadest daily), positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days), and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5th day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days). On day 65 levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) were measured. Also, kidney samples were collected for histopathological studies. Results: The results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules) compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats. Conclusion: From the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats. PMID:29299200

Homemade-device-induced negative pressure promotes wound healing more efficiently than VSD-induced positive pressure by regulating inflammation, proliferation and remodeling

PubMed Central

Liu, Jinyan; Hu, Feng; Tang, Jintian; Tang, Shijie; Xia, Kun; Wu, Song; Yin, Chaoqi; Wang, Shaohua; He, Quanyong; Xie, Huiqing; Zhou, Jianda

2017-01-01

Vacuum sealing drainage (VSD) is an effective technique used to promote wound healing. However, recent studies have shown that it exerts positive pressure (PP) rather than negative pressure (NP) on skin. In this study, we created a homemade device that could maintain NP on the wound, and compared the therapeutic effects of VSD-induced PP to those of our home-made device which induced NP on wound healing. The NP induced by our device required less time for wound healing and decreased the wound area more efficiently than the PP induced by VSD. NP and PP both promoted the inflammatory response by upregulating neutrophil infiltration and interleukin (IL)-1β expression, and downregulating IL-10 expression. Higher levels of epidermal growth factor (EGF), transforming growth factor (TGF)-β and platelet-derived growth factor (PDGF), and lower levels of basic fibroblast growth factor (bFGF) were observed in the wound tissue treated with NP compared to the wound tissue exposed to PP. Proliferation in the wound tissue exposed to NP on day 10 was significantly higher than that in wound tissue exposed to PP. NP generated more fibroblasts, keratinized stratified epithelium, and less epithelia with stemness than PP. The levels of ccollagen I and III were both decreased in both the NP and PP groups. NP induced a statistically significant increase in the expression of fibronectin (FN) on days 3 and 10 compared to PP. Furthermore, the level of matrix metalloproteinase (MMP)-13 increased in the NP group, but decreased in the PP group on day 3. NP also induced a decrease in the levels of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 during the early stages of wound healing, which was significantly different from the increasing effect of PP on TIMP-1 and TIMP-2 levels at the corresponding time points. On the whole, our data indicate that our homemade device which induced NP, was more efficient than VSD-induced PP on wound healing by regulating inflammation, secretion, proliferation and the distribution of different cells in wound tissue. PMID:28290607

Plasma action on helium flow in cold atmospheric pressure plasma jet experiments

NASA Astrophysics Data System (ADS)

Darny, T.; Pouvesle, J.-M.; Fontane, J.; Joly, L.; Dozias, S.; Robert, E.

2017-10-01

In this work, helium flow modifications, visualized by schlieren imaging, induced by the plasma generated in a plasma jet have been studied in conditions used for biomedical treatments (jet being directed downwards with a low helium flow rate). It has been shown that the plasma action can shift up to few centimeters downstream the effects of buoyancy, which allows to the helium flow to reach a target below in conditions for which it is not the case when the plasma is off. This study reveals the critical role of large and long lifetime negative ions during repetitive operations in the kHz regime, inducing strong modifications in the gas propagation. The cumulative added streamwise momentum transferred to ambient air surrounding molecules resulting from a series of applied voltage pulses induces a gradual built up of a helium channel on tens of millisecond timescale. In some conditions, a remarkable stable cylindrical helium channel can be generated to the target with plasma supplied by negative polarity voltage pulses whereas a disturbed flow results from positive polarity operation. This has a direct effect on air penetration in the helium channel and then on the reactive species production over the target which is of great importance for biomedical applications. It has also been shown that with an appropriate combination of negative and positive polarity pulses, it is possible to benefit from both polarity features in order to optimize the plasma plume propagation and plasma delivery to a target.

A Review on the Effect of Traditional Chinese Medicine Against Anthracycline-Induced Cardiac Toxicity

PubMed Central

Yang, Xinyu; Liu, Nian; Li, Xinye; Yang, Yihan; Wang, Xiaofeng; Li, Linling; Jiang, Le; Gao, Yonghong; Tang, Hebin; Tang, Yong; Xing, Yanwei; Shang, Hongcai

2018-01-01

Anthracyclines are effective agents generally used to treat solid-tumor and hematologic malignancies. The use of anthracyclines for over 40 years has improved cancer survival statistics. Nevertheless, the clinical utility of anthracyclines is limited by its dose-dependent cardiotoxicity that adversely affects 10–30% of patients. Anthracycline-induced cardiotoxicity may be classified as acute/subacute or chronic/late toxicity and leads to devastating adverse effects resulting in poor quality of life, morbidity, and premature mortality. Traditional Chinese medicine has a history of over 2,000 years, involving both unique theories and substantial experience. Several studies have investigated the potential of natural products to decrease the cardiotoxic effects of chemotherapeutic agents on healthy cells, without negatively affecting their antineoplastic activity. This article discusses the mechanism of anthracycline-induced cardiotoxicity, and summarizes traditional Chinese medicine treatment for anthracycline-induced heart failure (HF), cardiac arrhythmia, cardiomyopathy, and myocardial ischemia in recent years, in order to provide a reference for the clinical prevention and treatment of cardiac toxicity. PMID:29867456

[Effects of long time different negative pressures on osteogenic differentiation of rabbit bone mesenchymal stem cells].

PubMed

Zhao, Bowen; Zhang, Hongwei; Xu, Qiang; Ge, Quanhu; Li, Bolong; Peng, Xinyu; Wu, Xiangwei

2017-05-01

To investigate the effects of long time different negative pressures on osteogenic diffe-rentiation of rabbit bone mesenchymal stem cells (BMSCs). The rabbit BMSCs were isolated and cultured by density gradient centrifugation. Flow cytometry was used to analyze expression of surface markers. The third passage cells cultured under condition of osteogenic induction and under different negative pressure of 0 mm Hg (control group), 75 mm Hg (low negative pressure group), and 150 mm Hg (high negative pressure group) (1 mm Hg=0.133 kPa), and the negative pressure time was 30 min/h. Cell growth was observed under phase contrast microscopy, and the growth curve was drawn; alkaline phosphatase (ALP) activity was detected by ELISA after induced for 3, 7, and 14 days. The mRNA and protein expressions of collagen type I (COL-I) and osteocalcin (OC) in BMSCs were analyzed by real-time fluorescence quantitative PCR and Western blot. The cultured cells were identified as BMSCs by flow cytometry. The third passage BMSCs exhibited typical long shuttle and irregular shape. Cell proliferation was inhibited with the increase of negative pressure. After induced for 4 days, the cell number of high negative pressure group was significantly less than that in control group and low negative pressure group ( P <0.05), but there was no significant difference between the low negative pressure group and the control group ( P >0.05); at 5-7 days, the cell number showed significant difference between 3 groups ( P <0.05). The greater the negative pressure was, the greater the inhibition of cell proliferation was. There was no significant difference in ALP activity between groups at 3 days after induction ( P >0.05); the ALP activity showed significant difference ( P <0.05) between the high negative pressure group and the control group at 7 days after induction; and significant difference was found in the ALP activity between 3 groups at 14 days after induction ( P <0.05). The greater the negative pressure was, the higher the ALP activity was. Real-time fluorescence quantitative PCR and Western blot detection showed that the mRNA and protein expressions of COL-I and OC protein were significantly higher in low negative pressure group and high negative pressure group than control group ( P <0.05), and in the high negative pressure group than the low negative pressure group ( P <0.05). With the increase of the negative pressure, the osteogenic differentiation ability of BMSCs increases gradually, but the cell proliferation is inhibited.

Deletion of protein tyrosine phosphatase 1B obliterates endoplasmic reticulum stress-induced myocardial dysfunction through regulation of autophagy.

PubMed

Wang, Shuyi; Chen, Xiyao; Nair, Sreejayan; Sun, Dongdong; Wang, Xiaoming; Ren, Jun

2017-12-01

Endoplasmic reticulum (ER) stress has been demonstrated to prompt various cardiovascular risks although the underlying mechanism remains elusive. Protein tyrosine phosphatase-1B (PTP1B) serves as an essential negative regulator for insulin signaling. This study examined the role of PTP1B in ER stress-induced myocardial anomalies and underlying mechanism involved with a focus on autophagy. WT and PTP1B knockout mice were subjected to the ER stress inducer tunicamycin (1mg/kg). Cardiac function was evaluated with echocardiography and an Ion-Optix MyoCam system. Western blot analysis was used to monitor the levels of ER stress, autophagy and insulin signaling including insulin receptor substrate (IRS), tribbles homolog 3 (TRIB3), Atg5/7, p62 and LC3-II. Our results showed that ER stress resulted in compromised echocardiographic and cardiomyocyte contractile function, intracellular Ca 2+ mishandling, ER stress, O 2 - production, apoptosis, the effects of which (with the exception of ER stress) were significantly attenuated or negated by PTP1B ablation. Levels of serine phosphorylation of IRS-1, TRIB3, Atg5/7, LC3B and the autophagy adaptor p62 were significantly upregulated while IRS-1 tyrosine phosphorylation was reduced by tunicamycin, the effect of which were obliterated by PTP1B ablation. In vitro study revealed that the autophagy inducer rapamycin and TRIB3 overexpression cancelled PTP1B ablation-offered beneficial effects on cardiomyocyte function or O 2 - production in murine cardiomyocytes or H9C2 myoblasts. Antioxidant or gene silencing of TRIB3 mimicked PTP1B ablation-induced protective effects. These findings collectively suggested that PTP1B ablation protects against ER stress-induced cardiac anomalies through regulation of autophagy. Copyright © 2017 Elsevier B.V. All rights reserved.

Procyanidin dimer B2-mediated IRAK-M induction negatively regulates TLR4 signaling in macrophages

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

Sung, Nak-Yun; Yang, Mi-So; Song, Du-Sub

Highlights: •Pro B2 elevated the expression of IRAK-M, a negative regulator of TLR signaling. •LPS-induced expression of cell surface molecules was inhibited by Pro B2. •LPS-induced production of pro-inflammatory cytokines was inhibited by Pro B2. •Pro B2 inhibited LPS-induced activation of MAPKs and NF-κB through IRAK-M. •Pro B2 inactivated naïve T cells by inhibiting LPS-induced cytokines via IRAK-M. -- Abstract: Polyphenolic compounds have been found to possess a wide range of physiological activities that may contribute to their beneficial effects against inflammation-related diseases; however, the molecular mechanisms underlying this anti-inflammatory activity are not completely characterized, and many features remain tomore » be elucidated. In this study, we investigated the molecular basis for the down-regulation of toll-like receptor 4 (TLR4) signal transduction by procyanidin dimer B2 (Pro B2) in macrophages. Pro B2 markedly elevated the expression of the interleukin (IL)-1 receptor-associated kinase (IRAK)-M protein, a negative regulator of TLR signaling. Lipopolysaccharide (LPS)-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II) and production of pro-inflammatory cytokines (tumor necrosis factor-α, IL-1β, IL-6, and IL-12p70) were inhibited by Pro B2, and this action was prevented by IRAK-M silencing. In addition, Pro B2-treated macrophages inhibited LPS-induced activation of mitogen-activated protein kinases such as extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase and the translocation of nuclear factor κB and p65 through IRAK-M. We also found that Pro B2-treated macrophages inactivated naïve T cells by inhibiting LPS-induced interferon-γ and IL-2 secretion through IRAK-M. These novel findings provide new insights into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and the immune-pharmacological role of Pro B2 in the immune response against the development and progression of many chronic diseases.« less

The Herbivore-Induced Plant Volatile Methyl Salicylate Negatively Affects Attraction of the Parasitoid Diadegma semiclausum

PubMed Central

Mumm, Roland; Poelman, Erik H.; Yang, Yue; Pichersky, Eran; Dicke, Marcel

2010-01-01

The indirect defense mechanisms of plants comprise the production of herbivore-induced plant volatiles that can attract natural enemies of plant attackers. One of the often emitted compounds after herbivory is methyl salicylate (MeSA). Here, we studied the importance of this caterpillar-induced compound in the attraction of the parasitoid wasp Diadegma semiclausum by using a mutant Arabidopsis line. Pieris rapae infested AtBSMT1-KO mutant Arabidopsis plants, compromised in the biosynthesis of MeSA, were more attractive to parasitoids than infested wild-type plants. This suggests that the presence of MeSA has negative effects on parasitoid host-finding behavior when exposed to wild-type production of herbivore-induced Arabidopsis volatiles. Furthermore, in line with this, we recorded a positive correlation between MeSA dose and repellence of D. semiclausum when supplementing the headspace of caterpillar-infested AtBSMT1-KO plants with synthetic MeSA. Electronic supplementary material The online version of this article (doi:10.1007/s10886-010-9787-1) contains supplementary material, which is available to authorized users. PMID:20407809

Repression of Osteoblast Maturation by ERRα Accounts for Bone Loss Induced by Estrogen Deficiency

PubMed Central

Gallet, Marlène; Saïdi, Soraya; Haÿ, Eric; Photsavang, Johann; Marty, Caroline; Sailland, Juliette; Carnesecchi, Julie; Tribollet, Violaine; Barenton, Bruno; Forcet, Christelle; Birling, Marie-Christine; Sorg, Tania; Chassande, Olivier; Cohen-Solal, Martine; Vanacker, Jean-Marc

2013-01-01

ERRα is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRα negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRα on osteoblast maturation are responsible for one or both types of in vivo induced bone loss. To this end we have generated conditional knock out mice in which the receptor is normally present during early osteoblast differentiation but inactivated upon osteoblast maturation. Bone ageing in these animals was similar to that observed for control animals. In contrast conditional ERRαKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation), but not early (commitment), negative effects of ERRα on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency. PMID:23359549

Functional characterization of bovine TIRAP and MyD88 in mediating bacterial lipopolysaccharide-induced endothelial NF-kappaB activation and apoptosis.

PubMed

Cates, Elizabeth A; Connor, Erin E; Mosser, David M; Bannerman, Douglas D

2009-11-01

Mastitis is a prevalent disease in dairy cows. Gram-negative bacteria, which express the pro-inflammatory molecule lipopolysaccharide (LPS), are responsible for the majority of acute clinical cases of mastitis. Previous studies have identified differential susceptibility of human and bovine endothelial cells (EC) to the pro-inflammatory and injury-inducing effects of LPS. The Toll-like receptor (TLR)-4 signaling pathway, which is activated by LPS, has been well studied in humans, but not in ruminants. Human myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-kappaB and apoptotic signaling pathways. To assess the role of the bovine orthologs of these proteins in bovine TLR-4 signaling, dominant-negative constructs were expressed in bovine EC, and LPS-induced NF-kappaB activation and apoptosis evaluated. The results from this study indicate that bovine MyD88 and TIRAP play functional roles in transducing LPS signaling from TLR-4 to downstream effector molecules involved in NF-kappaB activation, and that TIRAP promotes apoptotic signaling.

Experimental modification of interpretation bias about animal fear in young children: effects on cognition, avoidance behavior, anxiety vulnerability, and physiological responding.

PubMed

Lester, Kathryn J; Field, Andy P; Muris, Peter

2011-01-01

This study investigated the effects of experimentally modifying interpretation biases for children's cognitions, avoidance behavior, anxiety vulnerability, and physiological responding. Sixty-seven children (6-11 years) were randomly assigned to receive a positive or negative interpretation bias modification procedure to induce interpretation biases toward or away from threat about ambiguous situations involving Australian marsupials. Children rapidly learned to select outcomes of ambiguous situations, which were congruent with their assigned condition. Furthermore, following positive modification, children's threat biases about novel ambiguous situations significantly decreased, whereas threat biases significantly increased after negative modification. In response to a stress-evoking behavioral avoidance test, positive modification attenuated behavioral avoidance compared to negative modification. However, no significant effects of bias modification on anxiety vulnerability or physiological responses to this stress-evoking Behavioral Avoidance Task were observed.

The effect of a major cigarette price change on smoking behavior in california: a zero-inflated negative binomial model.

PubMed

Sheu, Mei-Ling; Hu, Teh-Wei; Keeler, Theodore E; Ong, Michael; Sung, Hai-Yen

2004-08-01

The objective of this paper is to determine the price sensitivity of smokers in their consumption of cigarettes, using evidence from a major increase in California cigarette prices due to Proposition 10 and the Tobacco Settlement. The study sample consists of individual survey data from Behavioral Risk Factor Survey (BRFS) and price data from the Bureau of Labor Statistics between 1996 and 1999. A zero-inflated negative binomial (ZINB) regression model was applied for the statistical analysis. The statistical model showed that price did not have an effect on reducing the estimated prevalence of smoking. However, it indicated that among smokers the price elasticity was at the level of -0.46 and statistically significant. Since smoking prevalence is significantly lower than it was a decade ago, price increases are becoming less effective as an inducement for hard-core smokers to quit, although they may respond by decreasing consumption. For those who only smoke occasionally (many of them being young adults) price increases alone may not be an effective inducement to quit smoking. Additional underlying behavioral factors need to be identified so that more effective anti-smoking strategies can be developed.

Resting Sympathetic Baroreflex Sensitivity in Subjects with Low and High Tolerance to Central Hypovolemia Induced by Lower Body Negative Pressure

DTIC Science & Technology

2014-06-01

high tolerance to central hypovolemia induced by lower body negative pressure Carmen Hinojosa-Laborde1*, Kathy L. Ryan1, Caroline A. Rickards2 and...patients with high tolerance. Using lower body negative pressure (LBNP) as an experimental model to induce central hypovolemia, we have shown that...hypovolemia is associated with mainte- nance of adequate perfusion pressure (i.e., arterial blood pres- sure) to vital organs. Therefore, we hypothesize that

Cognitive Facilitation Following Intentional Odor Exposure

PubMed Central

Johnson, Andrew J.

2011-01-01

This paper reviews evidence that, in addition to incidental olfactory pollutants, intentional odor delivery can impact cognitive operations both positively and negatively. Evidence for cognitive facilitation/interference is reviewed alongside four potential explanations for odor-induced effects. It is concluded that the pharmacological properties of odors can induce changes in cognition. However, these effects can be accentuated/attenuated by the shift in mood following odor exposure, expectancy of cognitive effects, and cues to behavior via the contextual association with the odor. It is proposed that greater consideration is required in the intentional utilization of odors within both industrial and private locations, since differential effects are observed for odors with positive hedonic qualities. PMID:22163909

Behavior and nutritional condition buffer a large-bodied endotherm against direct and indirect effects of climate

Treesearch

Ryan A. Long; R. Terry Bowyer; Warren P. Porter; Paul Mathewson; Kevin L. Monteith; John G. Kie

2014-01-01

Temporal changes in net energy balance of animals strongly influence fitness; consequently, natural selection should favor behaviors that increase net energy balance by buffering individuals against negative effects of environmental variation. The relative importance of behavioral responses to climate-induced variation in costs vs. supplies of energy, however, is...

Effects of cortisol and lipopolysaccharide on expression of select growth-, stress- and immune-related genes in rainbow trout liver

USDA-ARS?s Scientific Manuscript database

Many studies have shown that stress-induced cortisol levels negatively influence growth and immunity in finfish. Despite this knowledge, few studies have assessed the direct effects of cortisol on liver immune function in finfish. Using real-time PCR, the expression of three cortisol-responsive ge...

Lactoferricin B causes depolarization of the cytoplasmic membrane of Escherichia coli ATCC 25922 and fusion of negatively charged liposomes.

PubMed

Ulvatne, H; Haukland, H H; Olsvik, O; Vorland, L H

2001-03-09

Antimicrobial peptides have been extensively studied in order to elucidate their mode of action. Most of these peptides have been shown to exert a bactericidal effect on the cytoplasmic membrane of bacteria. Lactoferricin is an antimicrobial peptide with a net positive charge and an amphipatic structure. In this study we examine the effect of bovine lactoferricin (lactoferricin B; Lfcin B) on bacterial membranes. We show that Lfcin B neither lyses bacteria, nor causes a major leakage from liposomes. Lfcin B depolarizes the membrane of susceptible bacteria, and induces fusion of negatively charged liposomes. Hence, Lfcin B may have additional targets responsible for the antibacterial effect.

Effects of gramicidin-A on the adsorption of phospholipids to the air–water interface

PubMed Central

Biswas, Samares C.; Rananavare, Shankar B.; Hall, Stephen B.

2012-01-01

Prior studies suggest that the hydrophobic surfactant proteins, SP-B and SP-C, promote adsorption of the lipids in pulmonary surfactant to an air–water interface by stabilizing a negatively curved rate-limiting structure that is intermediate between bilayer vesicles and the surface film. This model predicts that other peptides capable of stabilizing negative curvature should also promote lipid adsorption. Previous reports have shown that under appropriate conditions, gramicidin-A (GrA) induces dioleoyl phosphatidylcholine (DOPC), but not dimyristoyl phosphatidylcholine (DMPC), to form the negatively curved hexagonal-II (HII) phase. The studies reported here determined if GrA would produce the same effects on adsorption of DMPC and DOPC that the hydrophobic surfactant proteins have on the surfactant lipids. Small angle X-ray scattering and 31P-nuclear magnetic resonance confirmed that at the particular conditions used to study adsorption, GrA induced DOPC to form the HII phase, but DMPC remained lamellar. Measurements of surface tension showed that GrA in vesicles produced a general increase in the rate of adsorption for both phospholipids. When restricted to the interface, however, in preexisting films, GrA with DOPC, but not with DMPC, replicated the ability of the surfactant proteins to promote adsorption of vesicles containing only the lipids. The correlation between the structural and functional effects of GrA with the two phospholipids, and the similar effects on adsorption of GrA with DOPC and the hydrophobic surfactant proteins with the surfactant lipids fit with the model in which SP-B and SP-C facilitate adsorption by stabilizing a rate-limiting intermediate with negative curvature. PMID:16242116

Substance P Receptor Signaling Mediates Doxorubicin-Induced Cardiomyocyte Apoptosis and Triple-Negative Breast Cancer Chemoresistance

PubMed Central

Robinson, Prema; Kasembeli, Moses; Bharadwaj, Uddalak; Engineer, Nikita; Eckols, Kris T.; Tweardy, David J.

2016-01-01

Doxorubicin (DOX), an anthracycline, is broadly considered the most active single agent available for treating breast cancer but has been known to induce cardiotoxicity. Although DOX is highly effective in treating triple-negative breast cancer (TNBC), DOX can have poor outcomes owing to induction of chemoresistance. There is an urgent need to develop new therapies for TNBC aimed at improving DOX outcome and DOX-induced cardiotoxicity. Substance P (SP), a neuropeptide involved in pain transmission is known to stimulate production of reactive oxygen species (ROS). Elevated cardiac ROS is linked with heart injury and failure. We investigated the role of SP in chemotherapy-associated death of cardiomyocytes and chemoresistance. We showed that pretreating a cardiomyocyte cell line (H9C2) and a TNBC cell line (MDA-MB 231) with aprepitant, a SP receptor antagonist that is routinely used to treat chemotherapy-associated associated nausea, decreased DOX-induced reduction of cell viability, apoptotic cell death, and ROS production in cardiomyocytes and increased DOX-induced reduction of cell viability, apoptotic cell death, and ROS production in TNBC cells compared with cells treated with DOX alone. Our findings demonstrate the ability of aprepitant to decrease DOX-induced killing of cardiomyocytes and to increase cancer cell sensitivity to DOX, which has tremendous clinical significance. PMID:26981525

Heat shock protein 90 (HSP90) is overexpressed in p16-negative oropharyngeal squamous cell carcinoma, and its inhibition in vitro potentiates the effects of chemoradiation.

PubMed

Patel, Kirtesh; Wen, Jing; Magliocca, Kelly; Muller, Susan; Liu, Yuan; Chen, Zhuo Georgia; Saba, Nabil; Diaz, Roberto

2014-11-01

Cisplatin and radiation therapy remain the current standard for treating locally advanced SCCHN. Novel treatment approaches are needed, especially in patients with human papilloma virus (HPV)-negative disease who have worse outcomes despite multimodality therapy. Using our institutional review board approved database, we obtained twenty oropharyngeal squamous cell carcinoma (SCC) tissue samples: ten p16 positive, ten p16-negative. Because p16 expression is strongly associated with HPV positivity in oropharyngeal SCC, p16 status was used as a marker of HPV. We subsequently analyzed, via immunohistochemistry, heat shock protein 90 (HSP90) protein levels. Using HPV-positive and HPV-negative SCC cell lines, we compared baseline HSP90 expression levels and the effect of the HSP90 inhibitor ganetespib on viability and apoptosis. Clonogenic survival of HPV-negative cells treated with ganetespib, radiation therapy, and/or cisplatin was then investigated. We characterize the effects of ganetespib on proteins that are thought to drive DNA damage resistance in HPV-negative cells. HSP90 expression was significantly higher in p16-negative compared with p16-positive samples (p = 0.016) and in HPV-negative cell lines compared with positive cells. Ganetespib increased cytotoxicity and induced apoptosis in HPV-negative more than positive cells. Adding ganetespib to cisplatin and/or radiation therapy in HPV-negative cells further decreased clonogenic survival. Finally, ganetespib downregulated expressions of EGFR, ERK, AKT, p53, and HIF-1α. Ganetespib inhibited HPV-negative SCCHN viability and potentiated cell kill when combined with cisplatin or radiation therapy in vitro. With HSP90 expression higher in HPV-negative cells and in p16-negative patients, further exploration of the clinical activity of HSP90 inhibitors in SCCHN is warranted.

A dexamethasone-regulated gene signature is prognostic for poor survival in glioblastoma patients

PubMed Central

Luedi, Markus M.; Singh, Sanjay K.; Mosley, Jennifer C.; Hatami, Masumeh; Gumin, Joy; Sulman, Erik P.; Lang, Frederick F.; Stueber, Frank; Zinn, Pascal O.; Colen, Rivka R.

2016-01-01

Background Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. Methods We utilized three independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in TCGA and REMBRANDT databases. In silico connectivity Map analysis identified camptothecin as antagonist to dexamethasone induced negative effects. Results Pathway analyses predicted an activation of dexamethasone network (z-score:2.908). Top activated canonical pathways included ‘role of BRCA1 in DNA damage response’ (p=1.07E-04). GSCs were protected against temozolomide-induced apoptosis when co-incubated with dexamethasone. Altered cellular functions included cell-movement, cell-survival, and apoptosis with z-scores of 2.815, 5.137, and −3.122 respectively. CEBPB was activated in a dose dependent manner specifically in slow-dividing ‘stem-like’ cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk score had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone effects. Conclusions Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects. PMID:27653222

Prevention of TGF-beta-induced apoptosis by interlukin-4 through Akt activation and p70S6K survival signaling pathways.

PubMed

Lin, Sue-Jane; Chang, Chungming; Ng, Ah-Kau; Wang, Shu-Han; Li, Jia-Je; Hu, Cheng-po

2007-09-01

In this study, we demonstrate that interleukin-4 (IL-4) protects human hepatocellular carcinoma (HCC) cell line Hep3B from apoptosis induced by transforming growth factor-beta (TGF-beta). Further investigation of IL-4-transduced signaling pathways revealed that both insulin response substrate 1 and 2 (IRS-1/-2) and extracellular signal-regulated kinase (ERK) pathways were activated after IL-4 stimulation. The IRS-1/-2 activation was accompanied by the activation of phosphotidylinositol-3-kinase (PI3K), leading to Akt and p70 ribosomal protein S6 kinase (p70S6K). Interestingly, a protein kinase C (PKC) inhibitor, Gö6976, inhibited the phosphorylation of Akt, suggesting that the Akt activation was PKC-dependent. Using specific inhibitors for PI3K or ERK, we demonstrated that the PI3K pathway, but not the ERK pathway, was required for protection. The constitutively active form of PI3K almost completely rescued TGF-beta-induced apoptosis, further supporting the importance of the PI3K pathway in the protective effect of IL-4. Furthermore, a dominant negative Akt and/or Gö6976 only partially blocked the anti-apoptotic effect of IL-4. Similarly, rapamycin, which interrupted the activation of p70S6K, also only partially blocked the protective effect of IL-4. However, in the presence of both rapamycin and dominant negative Akt with or without Gö6976, IL-4 almost completely lost the anti-apoptotic effect, suggesting that both Akt and p70S6K pathways were required for the protective effect of IL-4 against TGF-beta-induced apoptosis.

Effect of direct current sputtering power on the behavior of amorphous indium-gallium-zinc-oxide thin-film transistors under negative bias illumination stress: A combination of experimental analyses and device simulation

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

Jang, Jun Tae; Kim, Dong Myong; Choi, Sung-Jin

The effect of direct current sputtering power of indium-gallium-zinc-oxide (IGZO) on the performance and stability of the corresponding thin-film transistor devices was studied. The field effect mobility increases as the IGZO sputter power increases, at the expense of device reliability under negative bias illumination stress (NBIS). Device simulation based on the extracted sub-gap density of states indicates that the field effect mobility is improved as a result of the number of acceptor-like states decreasing. The degradation by NBIS is suggested to be induced by the formation of peroxides in IGZO rather than charge trapping.

Usefulness of cardiotoxicity assessment using calcium transient in human induced pluripotent stem cell-derived cardiomyocytes.

PubMed

Watanabe, Hitoshi; Honda, Yayoi; Deguchi, Jiro; Yamada, Toru; Bando, Kiyoko

2017-01-01

Monitoring dramatic changes in intracellular calcium ion levels during cardiac contraction and relaxation, known as calcium transient, in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) would be an attractive strategy for assessing compounds on cardiac contractility. In addition, as arrhythmogenic compounds are known to induce characteristic waveform changes in hiPSC-CMs, it is expected that calcium transient would allow evaluation of not only compound-induced effects on cardiac contractility, but also compound arrhythmogenic potential. Using a combination of calcium transient in hiPSC-CMs and a fast kinetic fluorescence imaging detection system, we examined in this study changes in calcium transient waveforms induced by a series of 17 compounds that include positive/negative inotropic agents as well as cardiac ion channel activators/inhibitors. We found that all positive inotropic compounds induced an increase in peak frequency and/or peak amplitude. The effects of a negative inotropic compound could clearly be detected in the presence of a β-adrenergic receptor agonist. Furthermore, most arrhythmogenic compounds raised the ratio of peak decay time to peak rise time (D/R ratio) in calcium transient waveforms. Compound concentrations at which these parameters exceeded cutoff values correlated well with systemic exposure levels at which arrhythmias were reported to be evoked. In conclusion, we believe that peak analysis of calcium transient and determination of D/R ratio are reliable methods for assessing compounds' cardiac contractility and arrhythmogenic potential, respectively. Using these approaches would allow selection of compounds with low cardiotoxic potential at the early stage of drug discovery.

Fetal DNA does not induce preeclampsia-like symptoms when delivered in late pregnancy in the mouse.

PubMed

Čonka, Jozef; Konečná, Barbora; Lauková, Lucia; Vlková, Barbora; Celec, Peter

2017-04-01

The etiology of preeclampsia is unclear. Fetal DNA is present in higher concentrations in the plasma of pregnant women suffering from preeclampsia than in the plasma of healthy pregnant women. A previously published study has shown that human fetal DNA injected into pregnant mice induces preeclampsia-like symptoms when administered between gestation days 10-14. The aim of our experiment was to determine whether or not similar effects would be induced by administration of human and mouse fetal DNA, as well as mouse adult DNA and lipopolysaccharide during late pregnancy in the mouse. Experimental animals were injected daily intraperitoneally during gestation days 14-18 with either saline - negative control, lipopolysaccharide - positive control, or various types of DNA. On gestation day 19, blood pressure and proteinuria were measured, and placental and fetal weights were recorded. Fetal and placental hypotrophy were induced only by lipopolysaccharide (p < 0.001). Neither fetal nor adult DNA induced changes in fetal/placental weight. None of the experimental groups had higher blood pressure or urinary protein in comparison to saline treated animals. In our experiment, we found that there was no effect from intraperitoneally injected human fetal DNA, mouse fetal DNA, or mouse adult DNA on pregnant mice. Additionally, relatively high doses of various types of DNA did not induce preeclampsia-like symptoms in mice when administered in late pregnancy. Our negative results support the hypothesis that the increase of fetal DNA circulating in maternal circulation during the third trimester is rather a consequence than a cause of preeclampsia. Copyright © 2017 Elsevier Ltd. All rights reserved.

"Disorganized in time": impact of bottom-up and top-down negative emotion generation on memory formation among healthy and traumatized adolescents.

PubMed

Guillery-Girard, Bérengère; Clochon, Patrice; Giffard, Bénédicte; Viard, Armelle; Egler, Pierre-Jean; Baleyte, Jean-Marc; Eustache, Francis; Dayan, Jacques

2013-09-01

"Travelling in time," a central feature of episodic memory is severely affected among individuals with Post Traumatic Stress Disorder (PTSD) with two opposite effects: vivid traumatic memories are unorganized in temporality (bottom-up processes), non-traumatic personal memories tend to lack spatio-temporal details and false recognitions occur more frequently that in the general population (top-down processes). To test the effect of these two types of processes (i.e. bottom-up and top-down) on emotional memory, we conducted two studies in healthy and traumatized adolescents, a period of life in which vulnerability to emotion is particularly high. Using negative and neutral images selected from the international affective picture system (IAPS), stimuli were divided into perceptual images (emotion generated by perceptual details) and conceptual images (emotion generated by the general meaning of the material). Both categories of stimuli were then used, along with neutral pictures, in a memory task with two phases (encoding and recognition). In both populations, we reported a differential effect of the emotional material on encoding and recognition. Negative perceptual scenes induced an attentional capture effect during encoding and enhanced the recollective distinctiveness. Conversely, the encoding of conceptual scenes was similar to neutral ones, but the conceptual relatedness induced false memories at retrieval. However, among individuals with PTSD, two subgroups of patients were identified. The first subgroup processed the scenes faster than controls, except for the perceptual scenes, and obtained similar performances to controls in the recognition task. The second subgroup group desmonstrated an attentional deficit in the encoding task with no benefit from the distinctiveness associated with negative perceptual scenes on memory performances. These findings provide a new perspective on how negative emotional information may have opposite influences on memory in normal and traumatized individuals. It also gives clues to understand how intrusive memories and overgeneralization takes place in PTSD. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bortezomib sensitises TRAIL-resistant HPV-positive head and neck cancer cells to TRAIL through a caspase-dependent, E6-independent mechanism.

PubMed

Bullenkamp, J; Raulf, N; Ayaz, B; Walczak, H; Kulms, D; Odell, E; Thavaraj, S; Tavassoli, M

2014-10-23

Human papillomavirus (HPV) is causative for a new and increasing form of head and neck squamous cell carcinomas (HNSCCs). Although localised HPV-positive cancers have a favourable response to radio-chemotherapy (RT/CT), the impact of HPV in advanced or metastatic HNSCC remains to be defined and targeted therapeutics need to be tested for cancers resistant to RT/CT. To this end, we investigated the sensitivity of HPV-positive and -negative HNSCC cell lines to TRAIL (tumour necrosis factor-related apoptosis-inducing ligand), which induces tumour cell-specific apoptosis in various cancer types. A clear correlation was observed between HPV positivity and resistance to TRAIL compared with HPV-negative head and neck cancer cell lines. All TRAIL-resistant HPV-positive cell lines tested were sensitised to TRAIL-induced cell death by treatment with bortezomib, a clinically approved proteasome inhibitor. Bortezomib-mediated sensitisation to TRAIL was associated with enhanced activation of caspase-8, -9 and -3, elevated membrane expression levels of TRAIL-R2, cytochrome c release and G2/M arrest. Knockdown of caspase-8 significantly blocked cell death induced by the combination therapy, whereas the BH3-only protein Bid was not required for induction of apoptosis. XIAP depletion increased the sensitivity of both HPV-positive and -negative cells to TRAIL alone or in combination with bortezomib. In contrast, restoration of p53 following E6 knockdown in HPV-positive cells had no effect on their sensitivity to either single or combination therapy, suggesting a p53-independent pathway for the observed response. In summary, bortezomib-mediated proteasome inhibition sensitises previously resistant HPV-positive HNSCC cells to TRAIL-induced cell death through a mechanism involving both the extrinsic and intrinsic pathways of apoptosis. The cooperative effect of these two targeted anticancer agents therefore represents a promising treatment strategy for RT/CT-resistant HPV-associated head and neck cancers.

Negative expectations interfere with the analgesic effect of safety cues on pain perception by priming the cortical representation of pain in the midcingulate cortex

PubMed Central

Almarzouki, Abeer F.; Brown, Christopher A.; Brown, Richard J.; Leung, Matthew H. K.; Jones, Anthony K. P.

2017-01-01

It is well known that the efficacy of treatment effects, including those of placebos, is heavily dependent on positive expectations regarding treatment outcomes. For example, positive expectations about pain treatments are essential for pain reduction. Such positive expectations not only depend on the properties of the treatment itself, but also on the context in which the treatment is presented. However, it is not clear how the preceding threat of pain will bias positive expectancy effects. One hypothesis is that threatening contexts trigger fearful and catastrophic thinking, reducing the pain-relieving effects of positive expectancy. In this study, we investigated the disruptive influence of threatening contexts on positive expectancy effects while 41 healthy volunteers experienced laser-induced heat pain. A threatening context was induced using pain-threatening cues that preceded the induction of positive expectancies via subsequent pain-safety cues. We also utilised electroencephalography (EEG) to investigate potential neural mechanisms underlying these effects. Lastly, we used the Fear of Pain Questionnaire to address whether the disruptive effect of negative contexts on cued pain relief was related to the degree of fear of pain. As predicted, participants responded less to pain-safety cues (i.e., experienced more pain) when these were preceded by pain-threatening cues. In this threatening context, an enhancement of the N2 component of the laser-evoked potential was detected, which was more pronounced in fearful individuals. This effect was localised to the midcingulate cortex, an area thought to integrate negative affect with pain experience to enable adaptive behaviour in aversive situations. These results suggest that threatening contexts disrupt the effect of pain relief cues via an aversive priming mechanism that enhances neural responses in the early stages of sensory processing. PMID:28665973

Variable directionality of gene expression changes across generations does not constitute negative evidence of epigenetic inheritance.

PubMed

Sharma, Abhay

2015-01-01

Transgenerational epigenetic inheritance in mammals has been controversial due to inherent difficulties in its experimental demonstration. A recent report has, however, opened a new front in the ongoing debate by claiming that endocrine disrupting chemicals, contrary to previous findings, do not cause effects across generations. This claim is based on the observation that gene expression changes induced by these chemicals in the exposed and unexposed generations are mainly in the opposite direction. This analysis shows that the pattern of gene expression reported in the two generations is not expected by chance and is suggestive of transmission across generations. A meta-analysis of diverse data sets related to endocrine disruptor-induced transgenerational gene expression alterations, including the data provided in the said report, further suggests that effects of endocrine disrupting chemicals persist in unexposed generations. Based on the prior evidence of phenotypic variability and gene expression alterations in opposite direction between generations, it is argued here that calling evidence of mismatched directionality in gene expression in experiments testing potential of environmental agents in inducing epigenetic inheritance of phenotypic traits as negative is untenable. This is expected to settle the newly raised doubts over epigenetic inheritance in mammals.

One patient with schizophrenia showed reduced drug-induced extrapyramidal symptoms as a result of an alternative regimen of treatment with paliperidone 3 and 6 mg every other day.

PubMed

Suzuki, Hidenobu; Hibino, Hiroyuki; Inoue, Yuichi; Matsumoto, Hideo; Mikami, Katsunaka

2017-01-01

Schizophrenia is a chronic disease that requires long-term management with antipsychotics. Antipsychotic drugs are given by tapering their dose, extending the dosing interval, and so on, as part of a treatment strategy to minimize the adverse effects while at the same time maintaining efficacy. We report the case of one patient with schizophrenia in whom the clinical symptoms were alleviated after treatment with 6 mg paliperidone. However, the patient developed extrapyramidal syndrome, for which 3 and 6 mg paliperidone were administered alternately every other day. Extrapyramidal syndrome was assessed using the Drug-Induced Extrapyramidal Symptoms Scale, Abnormal Involuntary Movement Scale, or Barnes Akathisia Scale. There was improvement in Drug-Induced Extrapyramidal Symptoms Scale score and Abnormal Involuntary Movement Scale score. However, there was almost no change in the Positive and Negative Syndrome Scale total score, positive score, negative score, or general score. The results indicate the possibility of lessened adverse effects as a result of an alternative regimen of treatment with paliperidone 3 and 6 mg every other day in the maintenance phase.

Synergistic effects of direct and indirect defences on herbivore egg survival in a wild crucifer

PubMed Central

Fatouros, Nina E.; Pineda, Ana; Huigens, Martinus E.; Broekgaarden, Colette; Shimwela, Methew M.; Figueroa Candia, Ilich A.; Verbaarschot, Patrick; Bukovinszky, Tibor

2014-01-01

Evolutionary theory of plant defences against herbivores predicts a trade-off between direct (anti-herbivore traits) and indirect defences (attraction of carnivores) when carnivore fitness is reduced. Such a trade-off is expected in plant species that kill herbivore eggs by exhibiting a hypersensitive response (HR)-like necrosis, which should then negatively affect carnivores. We used the black mustard (Brassica nigra) to investigate how this potentially lethal direct trait affects preferences and/or performances of specialist cabbage white butterflies (Pieris spp.), and their natural enemies, tiny egg parasitoid wasps (Trichogramma spp.). Both within and between black mustard populations, we observed variation in the expression of Pieris egg-induced HR. Butterfly eggs on plants with HR-like necrosis suffered lower hatching rates and higher parasitism than eggs that did not induce the trait. In addition, Trichogramma wasps were attracted to volatiles of egg-induced plants that also expressed HR, and this attraction depended on the Trichogramma strain used. Consequently, HR did not have a negative effect on egg parasitoid survival. We conclude that even within a system where plants deploy lethal direct defences, such defences may still act with indirect defences in a synergistic manner to reduce herbivore pressure. PMID:25009068

Lack of nephroprotective efficacy of althaea officinalis flower extract against gentamicin renal toxicity in male rats.

PubMed

Talebi, Ardeshir; Karimi, Amirhossein; Ouguerram, Khadija; Vahidi-Ataabadi, Nasrin; Eshraghi-Jazi, Fatemeh; Mansouri, Azam; Nematbakhsh, Mehdi

2014-11-01

Gentamicin (GM) is used as antibiotic for Gram-negative infections, but its administration is limited due to a side-effect of nephrotoxicity. It was attempted to investigate the effect of Althaea officinalis flower extract (AOFE) against nephrotoxicity induced by GM in male rats. 30-year-old male Wistar rats were divided into five groups. Group 1 as a negative control group received AOFE 250 mg/kg/day. Groups 2-5 received saline, AOFE 50 mg/kg/day, AOFE 250 mg/kg/day, and AOFE 500 mg/kg/day for 9 days, respectively, and GM (100 mg/kg/day) was added from the 3(rd) day on. At the end of the experiment, blood samples were obtained, animals were sacrificed, and the kidneys were removed immediately. Gentamicin (in group 2) significantly increased serum levels of blood urea nitrogen and creatinine as well as the pathological damage score (P < 0.05) when compared with group 1. Low dose of AOFE did not decrease the nephrotoxicity induced by GM while the high dose of AOFE aggravated renal toxicity (P < 0.05). Although AOFE acts as an antioxidant, at the doses used in the current study did not ameliorate nephrotoxicity induced by GM.

Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect

PubMed Central

Gonano, Luis Alberto; Morell, Malena; Burgos, Juan Ignacio; Dulce, Raul Ariel; De Giusti, Verónica Celeste; Aiello, Ernesto Alejandro; Hare, Joshua Michael; Vila Petroff, Martin

2014-01-01

Aims Cardiomyocyte swelling occurs in multiple pathological situations and has been associated with contractile dysfunction, cell death, and enhanced propensity to arrhythmias. We investigate whether hypotonic swelling promotes nitric oxide (NO) release in cardiomyocytes, and whether it impacts on swelling-induced contractile dysfunction. Methods and results Superfusing rat cardiomyocytes with a hypotonic solution (HS; 217 mOsm), increased cell volume, reduced myocyte contraction and Ca2+ transient, and increased NO-sensitive 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate (DAF-FM) fluorescence. When cells were exposed to HS + 2.5 mM of the NO synthase inhibitor l-NAME, cell swelling occurred in the absence of NO release. Swelling-induced NO release was also prevented by the nitric oxide synthase 1 (NOS1) inhibitor, nitroguanidine, and significantly reduced in NOS1 knockout mice. Additionally, colchicine (inhibitor of microtubule polymerization) prevented the increase in DAF-FM fluorescence induced by HS, indicating that microtubule integrity is necessary for swelling-induced NO release. The swelling-induced negative inotropic effect was exacerbated in the presence of either l-NAME, nitroguandine, the guanylate cyclase inhibitor, ODQ, or the PKG inhibitor, KT5823, suggesting that NOS1-derived NO provides contractile support via a cGMP/PKG-dependent mechanism. Indeed, ODQ reduced Ca2+ wave velocity and both ODQ and KT5823 reduced the HS-induced increment in ryanodine receptor (RyR2, Ser2808) phosphorylation, suggesting that in this context, cGMP/PKG may contribute to preserve contractile function by enhancing sarcoplasmic reticulum Ca2+ release. Conclusions Our findings suggest a novel mechanism for NO release in cardiomyocytes with putative pathophysiological relevance determined, at least in part, by its capability to reduce the extent of contractile dysfunction associated with hypotonic swelling. PMID:25344365

The antipsychotic-like effects of positive allosteric modulators of metabotropic glutamate mGlu4 receptors in rodents

PubMed Central

Sławińska, Anna; Wierońska, Joanna M; Stachowicz, Katarzyna; Marciniak, Marcin; Łasoń-Tyburkiewicz, Magdalena; Gruca, Piotr; Papp, Mariusz; Kusek, Magdalena; Tokarski, Krzysztof; Doller, Darío; Pilc, Andrzej

2013-01-01

Background and Purpose Because agonists at metabotropic glutamate receptors exert beneficial effects in schizophrenia, we have assessed the actions of Lu AF21934 and Lu AF32615, two chemically distinct, selective and brain-penetrant positive allosteric modulators (PAMs) of the mGlu4 receptor, in several tests reflecting positive, negative and cognitive symptoms of schizophrenia in rodents. Experimental Approach Hyperactivity induced by MK-801 or amphetamine and head twitches induced by 2,5-dimethoxy-4-iodoamphetamine (DOI) in mice were used as models for positive symptoms. Disruption of social interaction and spatial delayed alternation tests induced by MK-801 in rats were used as models for negative and cognitive symptoms of schizophrenia, respectively. Key Results Lu AF21934 (0.1–5 mg·kg−1) and Lu AF32615 (2–10 mg·kg−1) dose-dependently inhibited hyperactivity induced by MK-801 or amphetamine. They also antagonized head twitches and increased frequency of spontaneous excitatory postsynaptic currents (EPSCs) in brain slices, induced by DOI. In mice lacking the mGlu4 receptor (mGlu4−/−) mice, Lu AF21934 did not antagonize DOI-induced head twitches. MK-801-induced disruption in the social interaction test was decreased by Lu AF21934 at 0.5 mg·kg−1 and by Lu AF32615 at 10 mg·kg−1. In the delayed spatial alternation test, Lu AF21934 was active at 1 and 2 mg·kg−1, while Lu AF32615 was active at 10 mg·kg−1. Conclusions and Implications We propose that activation by PAMs of the mGlu4 receptor is a promising approach to the discovery of novel antipsychotic drugs. PMID:23714045

Effect of infection with bovine leukosis virus on lymphocyte proliferation and apoptosis in dairy cattle.

PubMed

Erskine, Ronald J; Corl, Christine M; Gandy, Jeffery C; Sordillo, Lorraine M

2011-08-01

To determine effects of infection with bovine leukosis virus (BLV) on lymphocyte proliferation and apoptosis in dairy cattle. 27 adult Holstein cows. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood from lactating Holstein cows seronegative for BLV (n = 9 cows), seropositive for BLV and aleukemic (aleukemic; 9), and seropositive for BLV and persistently lymphocytotic (PL; 9). Isolated PBMCs were assayed for mitogen-induced proliferation and were analyzed by means of flow cytometry. The PBMCs from a subset of each group were assayed for apoptosis, caspase-9 activity, and expression of selected genes related to apoptosis. PL cows had significantly higher total lymphocyte counts and significantly lower proportions of T-lymphocyte populations than did BLV-negative and aleukemic cows. Both groups of BLV-infected cows had significantly higher proportions of B cells and major histocompatibility complex II-expressing cells than did BLV-negative cows. Proliferation with concanavalin A was significantly lower for PL cows, compared with proliferation for BLV-negative cows. Pokeweed mitogen-induced proliferation was significantly higher for aleukemic and PL cows than for BLV-negative cows. Gene expression of apoptosis-inhibitory proteins BCL2 and BCL2L1 was significantly higher for aleukemic cows and expression of BCL2 was significantly higher for PL cows than for BLV-negative cows. Cattle infected with BLV had marked changes in PBMC populations accompanied by alterations in proliferation and apoptosis mechanisms. Because the relative distribution and function of lymphocyte populations are critical for immune competence, additional studies are needed to investigate the ability of BLV-infected cattle to respond to infectious challenge.

Effects of experimentally induced low back pain on the sit-to-stand movement and electroencephalographic contingent negative variation

PubMed Central

Jacobs, Jesse V.; Yaguchi, Chie; Kaida, Chizuru; Irei, Mariko; Naka, Masami; Henry, Sharon M.; Fujiwara, Katsuo

2011-01-01

It is becoming increasingly evident that people with chronic, recurrent low back pain (LBP) exhibit changes in cerebrocortical activity that associate with altered postural coordination, suggesting a need for a better understanding of how the experience of LBP alters postural coordination and cerebrocortical activity. To characterize changes in postural coordination and pre-movement cerebrocortical activity related to the experience of acutely induced LBP, 14 healthy participants with no history of LBP performed sit-to-stand movements in 3 sequential conditions: (1) without experimentally induced LBP; NoPain1, (2) with movement-associated LBP induced by electrocutaneous stimulation; Pain, and (3) again without induced LBP; NoPain2. The Pain condition elicited altered muscle activation and redistributed forces under the seat and feet prior to movement, decreased peak vertical force exerted under the feet during weight transfer, longer movement times, as well as decreased and earlier peak hip extension. Stepwise regression models demonstrated that electroencephalographic amplitudes of contingent negative variation during the Pain condition significantly correlated with the participants’ change in sit-to-stand measures between the NoPain1 and Pain conditions, as well as with the subsequent difference in sit-to-stand measures between the NoPain1 and NoPain2 conditions. The results, therefore, identify the contingent negative variation as a correlate for the extent of an individual’s LBP-related movement modifications and to the subsequent change in movement patterns from before to after the experience of acutely induced LBP, thereby providing a direction for future studies aimed to understand the neural mechanisms underlying the development of altered movement patterns with LBP. PMID:21952791

Proper PIN1 Distribution Is Needed for Root Negative Phototropism in Arabidopsis

PubMed Central

Zhang, Kun-Xiao; Xu, Heng-Hao; Gong, Wen; Jin, Yan; Shi, Ya-Ya; Yuan, Ting-Ting; Li, Juan; Lu, Ying-Tang

2014-01-01

Plants can be adapted to the changing environments through tropic responses, such as light and gravity. One of them is root negative phototropism, which is needed for root growth and nutrient absorption. Here, we show that the auxin efflux carrier PIN-FORMED (PIN) 1 is involved in asymmetric auxin distribution and root negative phototropism. In darkness, PIN1 is internalized and localized to intracellular compartments; upon blue light illumination, PIN1 relocalize to basal plasma membrane in root stele cells. The shift of PIN1 localization induced by blue light is involved in asymmetric auxin distribution and root negative phototropic response. Both blue-light-induced PIN1 redistribution and root negative phototropism is mediated by a BFA-sensitive trafficking pathway and the activity of PID/PP2A. Our results demonstrate that blue-light-induced PIN1 redistribution participate in asymmetric auxin distribution and root negative phototropism. PMID:24465665

Proper PIN1 distribution is needed for root negative phototropism in Arabidopsis.

PubMed

Zhang, Kun-Xiao; Xu, Heng-Hao; Gong, Wen; Jin, Yan; Shi, Ya-Ya; Yuan, Ting-Ting; Li, Juan; Lu, Ying-Tang

2014-01-01

Plants can be adapted to the changing environments through tropic responses, such as light and gravity. One of them is root negative phototropism, which is needed for root growth and nutrient absorption. Here, we show that the auxin efflux carrier PIN-FORMED (PIN) 1 is involved in asymmetric auxin distribution and root negative phototropism. In darkness, PIN1 is internalized and localized to intracellular compartments; upon blue light illumination, PIN1 relocalize to basal plasma membrane in root stele cells. The shift of PIN1 localization induced by blue light is involved in asymmetric auxin distribution and root negative phototropic response. Both blue-light-induced PIN1 redistribution and root negative phototropism is mediated by a BFA-sensitive trafficking pathway and the activity of PID/PP2A. Our results demonstrate that blue-light-induced PIN1 redistribution participate in asymmetric auxin distribution and root negative phototropism.

Opioid-Induced Bowel Dysfunction

PubMed Central

Cheng, Vivian; Lembo, Anthony

2013-01-01

Opioid-induced bowel dysfunction (OIBD) is a potentially debilitating side effect of chronic opioid use. It refers to a collection of primarily gastrointestinal motility disorders induced by opioids, of which opioid-induced constipation (OIC) is the most common. Management of OIBD is difficult, and affected patients will often limit their opioid intake at the expense of experiencing more pain, to reduce the negative impact of OIBD on their quality of life. Effective pharmacologic therapy for OIC is considered an unmet need and several agents have recently been given priority review and approval for OIC. Furthermore, multiple agents currently in development show promise in treating OIC without significant impact on analgesia or precipitation of withdrawal symptoms. The approval and availability of such medications would represent a significant improvement in the management of OIC and OIBD in patients with chronic pain. PMID:23900996

Posttraumatic stress symptoms and tobacco abstinence effects in a non-clinical sample: evaluating the mediating role of negative affect reduction smoking expectancies.

PubMed

Langdon, Kirsten J; Leventhal, Adam M

2014-11-01

The relation between posttraumatic stress symptoms and smoking is well documented but poorly understood. The present investigation sought to evaluate the impact of posttraumatic stress symptoms on subjective and behavioral tobacco abstinence effects both directly and indirectly through negative affect reduction smoking outcome expectancies. Participants included 275 (68.7% male; Mage =43.9, 10+ cig/day) adult non-treatment seeking smokers, who attended two counterbalanced laboratory sessions (16 h of smoking deprivation vs ad libitum smoking), during which they completed self-report measures of withdrawal symptoms and mood followed by a smoking lapse task in which they could earn money for delaying smoking and purchase cigarettes to smoke. Results supported a mediational pathway whereby higher baseline symptoms of posttraumatic stress predicted greater endorsement of expectancies that smoking will effectively reduce negative affect, which in turn predicted greater abstinence-provoked exacerbations in nicotine withdrawal symptoms and negative affect. Posttraumatic stress symptoms also predicted number of cigarettes purchased independent of negative affect reduction expectancies, but did not predict delaying smoking for money. Findings highlight tobacco abstinence effects as a putative mechanism underlying posttraumatic stress disorder (PTSD)-smoking comorbidity, indicate an important mediating role of beliefs for smoking-induced negative affect reduction, and shed light on integrated treatment approaches for these two conditions. © The Author(s) 2014.

Transient emotional events and individual affective traits affect emotion recognition in a perceptual decision-making task.

PubMed

Qiao-Tasserit, Emilie; Garcia Quesada, Maria; Antico, Lia; Bavelier, Daphne; Vuilleumier, Patrik; Pichon, Swann

2017-01-01

Both affective states and personality traits shape how we perceive the social world and interpret emotions. The literature on affective priming has mostly focused on brief influences of emotional stimuli and emotional states on perceptual and cognitive processes. Yet this approach does not fully capture more dynamic processes at the root of emotional states, with such states lingering beyond the duration of the inducing external stimuli. Our goal was to put in perspective three different types of affective states (induced affective states, more sustained mood states and affective traits such as depression and anxiety) and investigate how they may interact and influence emotion perception. Here, we hypothesized that absorption into positive and negative emotional episodes generate sustained affective states that outlast the episode period and bias the interpretation of facial expressions in a perceptual decision-making task. We also investigated how such effects are influenced by more sustained mood states and by individual affect traits (depression and anxiety) and whether they interact. Transient emotional states were induced using movie-clips, after which participants performed a forced-choice emotion classification task with morphed facial expressions ranging from fear to happiness. Using a psychometric approach, we show that negative (vs. neutral) clips increased participants' propensity to classify ambiguous faces as fearful during several minutes. In contrast, positive movies biased classification toward happiness only for those clips perceived as most absorbing. Negative mood, anxiety and depression had a stronger effect than transient states and increased the propensity to classify ambiguous faces as fearful. These results provide the first evidence that absorption and different temporal dimensions of emotions have a significant effect on how we perceive facial expressions.

Interferon Regulatory Factor 7 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy

PubMed Central

Jiang, Ding-Sheng; Liu, Yu; Zhou, Heng; Zhang, Yan; Zhang, Xiao-Dong; Zhang, Xiao-Fei; Chen, Ke; Gao, Lu; Peng, Juan; Gong, Hui; Chen, Yingjie; Yang, Qinglin; Liu, Peter P.; Fan, Guo-Chang; Zou, Yunzeng; Li, Hongliang

2017-01-01

Cardiac hypertrophy is a complex pathological process that involves multiple factors including inflammation and apoptosis. Interferon regulatory factor 7 (IRF7) is a multifunctional regulator that participates in immune regulation, cell differentiation, apoptosis, and oncogenesis. However, the role of IRF7 in cardiac hypertrophy remains unclear. We performed aortic banding in cardiac-specific IRF7 transgenic mice, IRF7 knockout mice, and the wild-type littermates of these mice. Our results demonstrated that IRF7 was downregulated in aortic banding–induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 48 hours. Accordingly, heart-specific overexpression of IRF7 significantly attenuated pressure overload–induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of IRF7 led to opposite effects. Moreover, IRF7 protected against angiotensin II–induced cardiomyocyte hypertrophy in vitro. Mechanistically, we identified that IRF7-dependent cardioprotection was mediated through IRF7 binding to inhibitor of κB kinase-β, and subsequent nuclear factor-κB inactivation. In fact, blocking nuclear factor-κB signaling with cardiac-specific inhibitors of κBαS32A/S36A super-repressor transgene counteracted the adverse effect of IRF7 deficiency. Conversely, activation of nuclear factor-κB signaling via a cardiac-specific conditional inhibitor of κB kinase-βS177E/S181E (constitutively active) transgene negated the antihypertrophic effect of IRF7 overexpression. Our data demonstrate that IRF7 acts as a novel negative regulator of pathological cardiac hypertrophy by inhibiting nuclear factor-κB signaling and may constitute a potential therapeutic target for pathological cardiac hypertrophy. PMID:24396025

Negative Regulation of Leptin-induced Reactive Oxygen Species (ROS) Formation by Cannabinoid CB1 Receptor Activation in Hypothalamic Neurons.

PubMed

Palomba, Letizia; Silvestri, Cristoforo; Imperatore, Roberta; Morello, Giovanna; Piscitelli, Fabiana; Martella, Andrea; Cristino, Luigia; Di Marzo, Vincenzo

2015-05-29

The adipocyte-derived, anorectic hormone leptin was recently shown to owe part of its regulatory effects on appetite-regulating hypothalamic neuropeptides to the elevation of reactive oxygen species (ROS) levels in arcuate nucleus (ARC) neurons. Leptin is also known to exert a negative regulation on hypothalamic endocannabinoid levels and hence on cannabinoid CB1 receptor activity. Here we investigated the possibility of a negative regulation by CB1 receptors of leptin-mediated ROS formation in the ARC. Through pharmacological and molecular biology experiments we report data showing that leptin-induced ROS accumulation is 1) blunted by arachidonyl-2'-chloroethylamide (ACEA) in a CB1-dependent manner in both the mouse hypothalamic cell line mHypoE-N41 and ARC neuron primary cultures, 2) likewise blocked by a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, troglitazone, in a manner inhibited by T0070907, a PPAR-γ antagonist that also inhibited the ACEA effect on leptin, 3) blunted under conditions of increased endocannabinoid tone due to either pharmacological or genetic inhibition of endocannabinoid degradation in mHypoE-N41 and primary ARC neuronal cultures from MAGL(-/-) mice, respectively, and 4) associated with reduction of both PPAR-γ and catalase activity, which are reversed by both ACEA and troglitazone. We conclude that CB1 activation reverses leptin-induced ROS formation and hence possibly some of the ROS-mediated effects of the hormone by preventing PPAR-γ inhibition by leptin, with subsequent increase of catalase activity. This mechanism might underlie in part CB1 orexigenic actions under physiopathological conditions accompanied by elevated hypothalamic endocannabinoid levels. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Transient emotional events and individual affective traits affect emotion recognition in a perceptual decision-making task

PubMed Central

Garcia Quesada, Maria; Antico, Lia; Bavelier, Daphne; Vuilleumier, Patrik; Pichon, Swann

2017-01-01

Both affective states and personality traits shape how we perceive the social world and interpret emotions. The literature on affective priming has mostly focused on brief influences of emotional stimuli and emotional states on perceptual and cognitive processes. Yet this approach does not fully capture more dynamic processes at the root of emotional states, with such states lingering beyond the duration of the inducing external stimuli. Our goal was to put in perspective three different types of affective states (induced affective states, more sustained mood states and affective traits such as depression and anxiety) and investigate how they may interact and influence emotion perception. Here, we hypothesized that absorption into positive and negative emotional episodes generate sustained affective states that outlast the episode period and bias the interpretation of facial expressions in a perceptual decision-making task. We also investigated how such effects are influenced by more sustained mood states and by individual affect traits (depression and anxiety) and whether they interact. Transient emotional states were induced using movie-clips, after which participants performed a forced-choice emotion classification task with morphed facial expressions ranging from fear to happiness. Using a psychometric approach, we show that negative (vs. neutral) clips increased participants’ propensity to classify ambiguous faces as fearful during several minutes. In contrast, positive movies biased classification toward happiness only for those clips perceived as most absorbing. Negative mood, anxiety and depression had a stronger effect than transient states and increased the propensity to classify ambiguous faces as fearful. These results provide the first evidence that absorption and different temporal dimensions of emotions have a significant effect on how we perceive facial expressions. PMID:28151976

Negative mood disrupts self- and reward-biases in perceptual matching.

PubMed

Sui, Jie; Ohrling, Erik; Humphreys, Glyn W

2016-01-01

There are established effects of self- and reward-biases even on simple perceptual matching tasks [Sui, J., He, X., & Humphreys, G. W. (2012). Perceptual effects of social salience: Evidence from self-prioritization effects on perceptual matching. Journal of Experimental Psychology, Human Perception and Performance, 38, 1105-1117]; however we know little about whether these biases can be modulated by particular interventions, and whether the biases then change in the same way. Here we assessed how the biases alter under conditions designed to induce negative mood. We had participants read a list of self-related negative or neutral mood statements [Velten, E. (1968). A laboratory task for induction of mood states. Behavior Research and Therapy, 6, 473-482] and also listen for 10 min to a passage of negative or neutral music, prior to carrying out perceptual matching with shapes associated to personal labels (self or stranger) or reward (£12 or £1). Responses to the self- and high-reward-associated shapes were selectively slower and less sensitive (d') following the negative mood induction procedures, and the decrease in mood correlated with decreases in the reaction time bias across "high saliency" (self and high-reward) stimuli. We suggest that negative mood may decrease self- and reward-biases through reducing attention to salient external stimuli.

Daidzein suppresses tumor necrosis factor-α induced migration and invasion by inhibiting hedgehog/Gli1 signaling in human breast cancer cells.

PubMed

Bao, Cheng; Namgung, Hyeju; Lee, Jaehoo; Park, Hyun-Chang; Ko, Jiwon; Moon, Heejung; Ko, Hyuk Wan; Lee, Hong Jin

2014-04-30

In breast cancer, the cytokine tumor necrosis factor-α (TNF-α) induces cell invasion, although the molecular basis of it has not been clearly elucidated. In this study, we investigated the role of daidzein in regulating TNF-α induced cell invasion and the underlying molecular mechanisms. Daidzein inhibited TNF-α induced cellular migration and invasion in estrogen receptor (ER) negative MCF10DCIS.com human breast cancer cells. TNF-α activated Hedgehog (Hh) signaling by enhancing Gli1 nuclear translocation and transcriptional activity, which resulted in increased invasiveness; these effects were blocked by daidzein and the Hh signaling inhibitors, cyclopamine and vismodegib. Moreover, these compounds suppressed TNF-α induced matrix metalloproteinase (MMP)-9 mRNA expression and activity. Taken together, mammary tumor cell invasiveness was stimulated by TNF-α induced activation of Hh signaling; these effects were abrogated by daidzein, which suppressed Gli1 activation, thereby inhibiting migration and invasion.

Absolute Negative Resistance Induced by Directional Electron-Electron Scattering in a Two-Dimensional Electron Gas

NASA Astrophysics Data System (ADS)

Kaya, Ismet I.; Eberl, Karl

2007-05-01

A three-terminal device formed by two electrostatic barriers crossing an asymmetrically patterned two-dimensional electron gas displays an unusual potential depression at the middle contact, yielding absolute negative resistance. The device displays momentum and current transfer ratios that far exceed unity. The observed reversal of the current or potential in the middle terminal can be interpreted as the analog of Bernoulli’s effect in a Fermi liquid. The results are explained by directional scattering of electrons in two dimensions.

A novel DNA vaccine for reduction of PRRSV-induced negative immunomodulatory effects: A proof of concept.

PubMed

Suradhat, Sanipa; Wongyanin, Piya; Kesdangsakonwut, Sawang; Teankum, Komkrich; Lumyai, Mongkol; Triyarach, Sittikorn; Thanawongnuwech, Roongroje

2015-07-31

Viral-induced interleukin (IL)-10 and regulatory T lymphocytes (Tregs) are believed to play a major role in shaping the immunological and clinical outcomes following Porcine Reproductive and Respiratory Syndrome virus (PRRSV) infection. Recently, it has been shown that PRRSV nucleocapsid (N) protein can induce IL-10 production which is essential for induction of PRRSV-specific Tregs. We hypothesized that immunity to N protein should reduce PRRSV-induced negative immunomodulatory effects which will be essential for establishing proper anti-PRRSV immunity in infected pigs. To investigate the immunomodulatory effects of DNA vaccine encoding a linearized, truncated form of PRRSV-N protein (pORF7t) which was designed to preferentially induce cell-mediated immunity against PRRSV N protein. Immunomodulatory effects of the novel DNA vaccine were investigated in an experimental vaccinated-challenged model. In addition, long-term immunomodulatory effects of the DNA vaccine were investigated in vaccinated pigs kept at the PRRSV-positive environment until the end of the fattening period. Pigs were vaccinated either prior to or following natural PRRSV infection. The results indicated that pORF7t could modulate the anti-PRRSV immune responses and promote the control of viral replication in the vaccinated-challenged pigs. Immunized pigs exhibited increased numbers of PRRSV-specific activated CD4(+)CD25(+) lymphocytes, reduced numbers of PRRSV-specific Tregs, and rapid viral clearance following infection. In a long-term study, regardless of the time of vaccination, DNA vaccine could modulate the host immune responses, resulted in enhanced PRRSV-specific IFN-γ producing cells, and reduced numbers of PRRSV-specific Tregs, without evidence of enhanced antibody responses. No vaccine adverse reaction was observed throughout the study. This study revealed the novel concept that PRRSV-specific immunity can be modulated by induction of cell-mediated immunity against the nucleocapsid protein. This concept could potentially benefit the development of PRRSV management and control strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Carbonation-induced weathering effect on cesium retention of cement paste

NASA Astrophysics Data System (ADS)

Park, S. M.; Jang, J. G.

2018-07-01

Carbonation is inevitable for cement and concrete in repositories over an extended period of time. This study investigated the carbonation-induced weathering effect on cesium retention of cement. Cement paste samples were exposed to accelerated carbonation for different durations to simulate the extent of weathering among samples. The extent of carbonation in cement was characterized by XRD, TG and NMR spectroscopy, while the retention capacity for cesium was investigated by zeta potential measurement and batch adsorption tests. Though carbonation led to decalcification from the binder gel, it negatively charged the surface of cement hydrates and enhanced their cesium adsorption capacity.

Effect of perzinfotel and a proprietary phospholipase A(2) inhibitor on kinetic gait and subjective lameness scores in dogs with sodium urate-induced synovitis.

PubMed

Budsberg, Steven C; Torres, Bryan T; Zwijnenberg, Raphael J; Eppler, C Mark; Clark, James D; Cathcart, Curtis J; Reynolds, Lisa R; Al-Nadaf, Sami

2011-06-01

To investigate the ability of perzinfotel (an N-methyl-d-aspartate receptor antagonist) and a proprietary phospholipase A(2) (PLA(2)) inhibitor to attenuate lameness in dogs with sodium urate (SU)-induced synovitis. 8 adult dogs. A blinded 4-way crossover study was performed. Dogs received perzinfotel (10 mg/kg), a proprietary PLA(2) inhibitor (10 mg/kg), carprofen (4.4 mg/kg; positive control treatment), or no treatment (negative control treatment). On the fourth day after initiation of treatment, synovitis was induced via intra-articular injection of SU 1 hour before administration of the last treatment dose. Ground reaction forces were measured and clinical lameness evaluations were performed before (baseline [time 0]) and 2, 4, 6, 8, 12, and 25 hours after SU injection. There was a 21-day washout period between subsequent treatments. Data were analyzed via repeated-measures ANOVAs. Peak vertical force (PVF) and vertical impulse (VI) values for negative control and perzinfotel treatments were significantly lower at 2 and 4 hours, compared with baseline values. Values for PVF and VI for the PLA(2) inhibitor and positive control treatments did not differ from baseline values at any time points. Between-treatment comparisons revealed significantly higher PVF and VI values for the positive control treatment than for the negative control and perzinfotel treatments at 2 and 4 hours. Values for VI were higher for PLA(2) inhibitor treatment than for negative control treatment at 2 hours. Perzinfotel did not significantly alter SU-induced lameness. The proprietary PLA(2) inhibitor attenuated lameness but not as completely as did carprofen.

The nocebo effect of drugs.

PubMed

Planès, Sara; Villier, Céline; Mallaret, Michel

2016-04-01

While the placebo effect has been studied for a long time, much less is known about its negative counterpart, named the nocebo effect. However, it may be of particular importance because of its impact on the treatment outcomes and public health. We conducted a review on the nocebo effect using PubMed and other databases up to July 2014. The nocebo effect refers by definition to the induction or the worsening of symptoms induced by sham or active therapies. Examples are numerous and concerns both clinical trials and daily practice. The underlying mechanisms are, on one hand, psychological (conditioning and negative expectations) and, on the other hand, neurobiological (role of cholecystokinin, endogenous opioids and dopamine). Nocebo effects can modulate the outcome of a given therapy in a negative way, as do placebo effects in a positive way. The verbal and nonverbal communications of physicians contain numerous unintentional negative suggestions that may trigger a nocebo response. This raises the important issue of how physicians can at the same time obtain informed consent and minimize nocebo-related risks. Every physician has to deal with this apparent contradiction between primum non nocere and to deliver truthful information about risks. Meticulous identification of patients at risk, information techniques such as positive framing, contextualized informed consent, and even noninformation, is valuable.

Multiple scattering induced negative refraction of matter waves

PubMed Central

Pinsker, Florian

2016-01-01

Starting from fundamental multiple scattering theory it is shown that negative refraction indices are feasible for matter waves passing a well-defined ensemble of scatterers. A simple approach to this topic is presented and explicit examples for systems of scatterers in 1D and 3D are stated that imply negative refraction for a generic incoming quantum wave packet. Essential features of the effective scattering field, densities and frequency spectrum of scatterers are considered. Additionally it is shown that negative refraction indices allow perfect transmission of the wave passing the ensemble of scatterers. Finally the concept of the superlens is discussed, since it is based on negative refraction and can be extended to matter waves utilizing the observations presented in this paper which thus paves the way to ‘untouchable’ quantum systems in analogy to cloaking devices for electromagnetic waves. PMID:26857266

Impact of hormonal crosstalk on plant resistance and fitness under multi-attacker conditions

PubMed Central

Vos, Irene A.; Moritz, Liselotte; Pieterse, Corné M. J.; Van Wees, Saskia C. M.

2015-01-01

The hormone salicylic acid (SA) generally induces plant defenses against biotrophic pathogens. Jasmonic acid (JA) and its oxylipin derivatives together with ethylene (ET) are generally important hormonal regulators of induced plant defenses against necrotrophic pathogens, whereas JAs together with abscisic acid (ABA) are implicated in induced plant defenses against herbivorous insects. Hormonal crosstalk between the different plant defense pathways has often been hypothesized to be a cost-saving strategy that has evolved as a means of the plant to reduce allocation costs by repression of unnecessary defenses, thereby minimizing trade-offs between plant defense and growth. However, proof for this hypothesis has not been demonstrated yet. In this study the impact of hormonal crosstalk on disease resistance and fitness of Arabidopsis thaliana when under multi-species attack was investigated. Induction of SA- or JA/ABA-dependent defense responses by the biotrophic pathogen Hyaloperonospora arabidopsidis or the herbivorous insect Pieris rapae, respectively, was shown to reduce the level of induced JA/ET-dependent defense against subsequent infection with the necrotrophic pathogen Botrytis cinerea. However, despite the enhanced susceptibility to this second attacker, no additional long-term negative effects were observed on plant fitness when plants had been challenged by multiple attackers. Similarly, when plants were grown in dense competition stands to enlarge fitness effects of induced defenses, treatment with a combination of SA and MeJA did not cause additional negative effects on plant fitness in comparison to the single MeJA treatment. Together, these data support the notion that hormonal crosstalk in plants during multi-attacker interactions allows plants to prioritize their defenses, while limiting the fitness costs associated with induction of defenses. PMID:26347758

Arctigenin protects against ultraviolet-A-induced damage to stemness through inhibition of the NF-κB/MAPK pathway.

PubMed

Park, See-Hyoung; Cho, Jae Youl; Oh, Sae Woong; Kang, Mingyeong; Lee, Seung Eun; Yoo, Ju Ah; Jung, Kwangseon; Lee, Jienny; Lee, Sang Yeol; Lee, Jongsung

2018-02-25

The stemness of stem cells is negatively affected by ultraviolet A (UVA) irradiation. This study was performed to examine the effects of arctigenin on UVA-irradiation-induced damage to the stemness of human mesenchymal stem cells (hMSCs) derived from adipose tissue. The mechanisms of action of arctigenin were also investigated. A BrdU-incorporation assay demonstrated that arctigenin attenuated the UVA-induced reduction of the cellular proliferative potential. Arctigenin also increased the UVA-induced reduction in stemness of hMSCs by upregulating stemness-related genes such as SOX2, OCT4, and NANOG. In addition, the UVA-induced reduction in the mRNA expression level of hypoxia-inducible factor (HIF)-1α was significantly recovered by arctigenin. The antagonizing effect of arctigenin on UVA irradiation was mediated by reduced PGE 2 production through the inhibition of MAPKs (p42/44 MAPK, p38 MAPK, and JNK) and NF-κB. Overall, these findings suggest that arctigenin can ameliorate the reduced stemness of hMSCs induced by UVA irradiation. The effects of arctigenin are mediated by PGE 2 -cAMP signaling-dependent upregulation of HIF-1α. Therefore, arctigenin could be used as an antagonist to attenuate the effects of UVA irradiation. Copyright © 2018 Elsevier B.V. All rights reserved.

Glutamatergic Deficits in Schizophrenia - Biomarkers and Pharmacological Interventions within the Ketamine Model.

PubMed

Haaf, Moritz; Leicht, Gregor; Curic, Stjepan; Mulert, Christoph

2018-06-19

The basic mechanism of pharmacotherapy in schizophrenia has barely changed in the last 60 years. Currently used medications allow the effective treatment of positive symptoms via antagonistic effects at dopamine receptors whereas the effect on negative and cognitive symptoms is most often negligible. The observation that N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists such as ketamine transiently induce schizophrenia-like positive, negative and cognitive symptoms has led to a paradigm shift from dopaminergic to glutamatergic dysfunction in pharmacological models of schizophrenia. The NMDAR hypofunction can explain not only the whole range of schizophrenia symptoms but also the dopaminergic dysfunction itself, and it emphasizes the need for pharmacologicallytargeted glutamatergic neurotransmission. Moreover, ketamine-induced psychopathological changes in healthy participants were accompanied by altered electro-(EEG), magnetoencephalographic (MEG) (e.g. Mismatch Negativity (MMN), N100), and functional magnetic resonance imaging (fMRI) signals, reminiscent of findings observed in patients with schizophrenia. Hence, the ketamine model offers the possibility to assess the effect of novel pharmacological agents on schizophrenia-like symptoms and neurophysiology, thereby potentially facilitating drug research and development by providing a way to ascertain functional target engagement and the ability to prioritize candidate drugs. Therefore, this review summarizes the recent evidence from EEG, MEG and fMRI studies on potential biomarkers found in healthy subjects treated with ketamine and pharmacological interventions within the ketamine model. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mood States Associated with Induced Defensiveness.

ERIC Educational Resources Information Center

Jaderlund, Natasha Slesnick; Waldron, Holly Barrett

1994-01-01

Compared effects of neutral and defensive mood induction in 70 students reporting conflicted versus nonconflicted families for presence of hostility, aggression, fear, anxiety, and sadness. Found that defensive students from high-conflict families reported stronger negative emotions than did neutral high-conflict and defensive low-conflict…

Effects of heat stress and insulin sensitizers on pig adipose tissue

USDA-ARS?s Scientific Manuscript database

Heat stress (HS) negatively impacts several swine production variables, including carcass fat quality. Pigs reared in HS have more adipose tissue than energetically predicted, explainable by HS-induced hyperinsulinemia. Study objectives were to evaluate insulin’s role in altering fat characteristics...

Taboo words: the effect of emotion on memory for peripheral information.

PubMed

Guillet, Rebecca; Arndt, Jason

2009-09-01

In three experiments, we examined memory for peripheral information that occurred in the same context as emotion-inducing information. In the first two experiments, participants studied either a sentence (Experiment 1) or a pair of words (Experiments 2A-2C) containing a neutral peripheral word, as well as a neutral, negative-valence, or taboo word, to induce an emotional response. At retrieval, the participants were asked to recall the neutral peripheral word from a sentence fragment or emotion-inducing word cue. In Experiment 3, we presented word pairs at encoding and tested memory with associative recognition. In all three experiments, memory for peripheral words was enhanced when it was encoded in the presence of emotionally arousing taboo words but not when it was encoded in the presence of words that were only negative in valence. These data are consistent with priority-binding theory (MacKay et al., 2004) and inconsistent with the attention-narrowing hypothesis (Easterbrook, 1959), as well as with object-based binding theory (Mather, 2007).

Peroxisome proliferator-activated receptor {alpha} agonist-induced down-regulation of hepatic glucocorticoid receptor expression in SD rats

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

Chen Xiang; Li Ming; Sun Weiping

2008-04-18

It was reported that glucocorticoid production was inhibited by fenofibrate through suppression of type-1 11{beta}-hydroxysteroid dehydrogenase gene expression in liver. The inhibition might be a negative-feedback regulation of glucocorticoid receptor (GR) activity by peroxisome proliferator-activated receptor alpha (PPAR{alpha}), which is quickly induced by glucocorticoid in the liver. However, it is not clear if GR expression is changed by fenofibrate-induced PPAR{alpha} activation. In this study, we tested this possibility in the liver of Sprague-Dawley rats. GR expression was reduced by fenofibrate in a time- and does-dependent manner. The inhibition was observed in liver, but not in fat and muscle. The corticosteronemore » level in the blood was increased significantly by fenofibrate. These effects of fenofibrate were abolished by PPAR{alpha} inhibitor MK886, suggesting that fenofibrate activated through PPAR{alpha}. In conclusion, inhibition of GR expression may represent a new molecular mechanism for the negative feedback regulation of GR activity by PPAR{alpha}.« less

Early effects of Lansoprazole orally disintegrating tablets on intragastric pH in CYP2C19 extensive metabolizers

PubMed Central

Yamagishi, Hatsushi; Koike, Tomoyuki; Ohara, Shuichi; Horii, Toru; Kikuchi, Ryousuke; Kobayashi, Shigeyuki; Abe, Yasuhiko; Iijima, Katsunori; Imatani, Akira; Suzuki, Kaori; Hishinuma, Takanori; Goto, Junichi; Shimosegawa, Tooru

2008-01-01

AIM: To compare rabeprazole (RPZ; 10 mg) with Lansoprazole orally disintegrating tablets (LPZ; 30 mg OD) in terms of antisecretory activity and blood drug concentration after a single dose. METHODS: Eight H pylori-negative cytochrome P450 (CYP) 2C19 extensive metabolizers were assigned to receive a single oral dose of RPZ 10 mg or LPZ 30 mg OD. Twelve hour intragastric pH monitoring was performed on the day of treatment. Blood samples were also collected after the administration of each drug. RESULTS: LPZ 30 mg OD induced a significantly earlier rise in blood drug concentration than RPZ 10 mg; consequently, LPZ 30 mg OD induced a significantly earlier rise in median pH in the third and fourth hours of the study. CONCLUSION: In H pylori-negative CYP2C19 extensive metabolizers, LPZ 30 mg OD induced a significantly faster inhibition of gastric acid secretion than RPZ 10 mg. PMID:18395905

Positive exchange-bias and giant vertical hysteretic shift in La0.3Sr0.7FeO3/SrRuO3 bilayers

PubMed Central

Rana, Rakesh; Pandey, Parul; Singh, R. P.; Rana, D. S.

2014-01-01

The exchange-bias effects in the mosaic epitaxial bilayers of the itinerant ferromagnet (FM) SrRuO3 and the antiferromagnetic (AFM) charge-ordered La0.3Sr0.7FeO3 were investigated. An uncharacteristic low-field positive exchange bias, a cooling-field driven reversal of positive to negative exchange-bias and a layer thickness optimised unusual vertical magnetization shift were all novel facets of exchange bias realized for the first time in magnetic oxides. The successive magnetic training induces a transition from positive to negative exchange bias regime with changes in domain configurations. These observations are well corroborated by the hysteretic loop asymmetries which display the modifications in the AFM spin correlations. These exotic features emphasize the key role of i) mosaic disorder induced subtle interplay of competing AFM-superexchange and FM double exchange at the exchange biased interface and, ii) training induced irrecoverable alterations in the AFM spin structure. PMID:24569516

How children use drawing to regulate their emotions.

PubMed

Drake, Jennifer E; Winner, Ellen

2013-01-01

We examined two ways in which drawing may function to elevate mood in children-venting (expressing negative feelings) and distraction (expressing something unrelated to the negative feelings). We examined the effectiveness of drawing as an emotion regulator when drawing is used to vent versus distract (Study 1) and tested whether the effects found are specific to the activity of creating one's own drawing or generalisable to a drawing activity in which children had to copy another's drawing (Study 2). To induce a negative mood, we asked children to think of a disappointing event. Mood was assessed before and after the assigned activity. In both studies, mood improved significantly more in the distract than in the vent or copy condition. Study 1 demonstrates that drawing improves mood in children via distraction and not via venting. Study 2 demonstrates that this effect is specific to a drawing task in which an image is freely constructed. When a copying task is used, the effect disappears.

Seeing the big picture: Broadening attention relieves sadness and depressed mood.

PubMed

Gu, Li; Yang, Xueling; Li, Liman Man Wai; Zhou, Xinyue; Gao, Ding-Guo

2017-08-01

We examined whether the broadened attentional scope would affect people's sad or depressed mood with two experiments, enlightened by the meaning of "seeing the big picture" and the broaden-and-build model. Experiment 1 (n = 164) is a laboratory-based experiment, in which we manipulated the attentional scope by showing participants zoomed-out or zoomed-in scenes. In Experiment 2 (n = 44), we studied how depressed mood and positive and negative emotions were affected when participants watched distant versus proximal scenes for eight weeks in real life. Healthy participants in Experiment 1, who were induced to feel sad, could return to the baseline mood after having the broadened attention task but not after having the narrowed attention task, which indicated that immediate attention broadening manipulation could function as antidotes for the lingering effects of induced negative emotions. Participants with depressed mood in Experiment 2 showed reduced depressed mood, increased positive affect, and decreased negative affect after receiving attention broadening training compared to those receiving attention narrowing training. Our findings suggest a robust role of broadened attentional scope in relieving negative emotions and even mildly depressed mood in the long run. © 2017 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Dominant Negative Pleiotrophin Induces Tetraploidy and Aneuploidy in U87MG Human Glioblastoma Cells

PubMed Central

Chang, Yunchao; Berenson, James R.; Wang, Zhaoyi; Deuel, Thomas F.

2007-01-01

Summary Pleiotrophin (PTN, Ptn) is an 18 kD secretory cytokine that is expressed in many human cancers, including glioblastoma. In previous experiments, interruption of the constitutive PTN signaling in human U87MG glioblastoma cells that inappropriately express endogenous Ptn reversed their rapid growth in vitro and their malignant phenotype in vivo. To seek a mechanism for the effect of the dominant negative PTN, flow cytometry was used to compare the profiles of U87MG cells and four clones of U87MG cells that express the dominant negative PTN (U87MG/PTN 1–40 cells); here, we report that the dominant negative PTN in U87MG cells induces tetraploidy and aneuploidy and arrests the tetraploid and aneuploid cells in the G1 phase of the cell cycle. The data suggest that PTN signaling may have a critical role in chromosomal segregation and cell cycle progression; the data suggest induction of tetraploidy and aneuploidy in U87MG glioblastoma cells may be an important mechanism that contributes to the loss of the malignant phenotype of U87MG cells. PMID:17067552

Exploring the impact of positive and negative emotions on cooperative behaviour in a Prisoner’s Dilemma Game

PubMed Central

Thompson, Sam

2013-01-01

Objective. To explore the influences of discrete positive and negative emotions on cooperation in the context of a social dilemma game. Design. Two controlled studies were undertaken. In Study 1, 69 participants were randomly assigned to an essay emotion manipulation task designed to induce either guilt, joy or no strong emotion. In Study 2, 95 participants were randomly assigned to one of the same three tasks, and the impact of emotional condition on cooperation was explored using a repeated Prisoner’s Dilemma Game. Results. Study 1 established that the manipulation task was successful in inducing the specified emotions. The analysis from Study 2 revealed no significant main effects for emotions, in contrast to previous research. However, there was a significant effect for participants’ pre-existing tendency to cooperate (social value orientation; SVO). Conclusion. Methodological explanations for the result are explored, including the possible impact of trial-and-error strategies, different cooperation games and endogenous vs exogenous emotions. PMID:24432196

Exploring the impact of positive and negative emotions on cooperative behaviour in a Prisoner's Dilemma Game.

PubMed

Kjell, Oscar N E; Thompson, Sam

2013-12-19

Objective. To explore the influences of discrete positive and negative emotions on cooperation in the context of a social dilemma game. Design. Two controlled studies were undertaken. In Study 1, 69 participants were randomly assigned to an essay emotion manipulation task designed to induce either guilt, joy or no strong emotion. In Study 2, 95 participants were randomly assigned to one of the same three tasks, and the impact of emotional condition on cooperation was explored using a repeated Prisoner's Dilemma Game. Results. Study 1 established that the manipulation task was successful in inducing the specified emotions. The analysis from Study 2 revealed no significant main effects for emotions, in contrast to previous research. However, there was a significant effect for participants' pre-existing tendency to cooperate (social value orientation; SVO). Conclusion. Methodological explanations for the result are explored, including the possible impact of trial-and-error strategies, different cooperation games and endogenous vs exogenous emotions.

The Implicit Positive and Negative Affect Test: Validity and Relationship with Cardiovascular Stress-Responses

PubMed Central

van der Ploeg, Melanie M.; Brosschot, Jos F.; Thayer, Julian F.; Verkuil, Bart

2016-01-01

Self-report, i.e., explicit, measures of affect cannot fully explain the cardiovascular (CV) responses to stressors. Measuring affect beyond self-report, i.e., using implicit measures, could add to our understanding of stress-related CV activity. The Implicit Positive and Negative Affect Test (IPANAT) was administered in two studies to test its ecological validity and relation with CV responses and self-report measures of affect. In Study 1 students (N = 34) viewed four film clips inducing anger, happiness, fear, or no emotion, and completed the IPANAT and the Positive And Negative Affect Scale at baseline and after each clip. Implicit negative affect (INA) was higher and implicit positive affect (IPA) was lower after the anger inducing clip and vice versa after the happiness inducing clip. In Study 2 students performed a stressful math task with (n = 14) or without anger harassment (n = 15) and completed the IPANAT and a Visual Analog Scale as an explicit measure afterwards. Systolic (SBP), diastolic (DBP) blood pressure, heart rate (HR), heart rate variability (HRV), and total peripheral resistance (TPR) were recorded throughout. SBP and DBP were higher and TPR was lower in the harassment condition during the task with a prolonged effect on SBP and DBP during recovery. As expected, explicit negative affect (ENA) was higher and explicit positive affect (EPA) lower after harassment, but ENA and EPA were not related to CV activity. Although neither INA nor IPA differed between the tasks, during both tasks higher INA was related to higher SBP, lower HRV and lower TPR and to slower recovery of DBP after both tasks. Low IPA was related to slower recovery of SBP and DBP after the tasks. Implicit affect was not related to recovery of HR, HRV, and TPR. In conclusion, the IPANAT seems to respond to film clip-induced negative and positive affect and was related to CV activity during and after stressful tasks. These findings support the theory that implicitly measured affect can add to the explanation of prolonged stress-related CV responses that influence CV health. PMID:27065908

The Implicit Positive and Negative Affect Test: Validity and Relationship with Cardiovascular Stress-Responses.

PubMed

van der Ploeg, Melanie M; Brosschot, Jos F; Thayer, Julian F; Verkuil, Bart

2016-01-01

Self-report, i.e., explicit, measures of affect cannot fully explain the cardiovascular (CV) responses to stressors. Measuring affect beyond self-report, i.e., using implicit measures, could add to our understanding of stress-related CV activity. The Implicit Positive and Negative Affect Test (IPANAT) was administered in two studies to test its ecological validity and relation with CV responses and self-report measures of affect. In Study 1 students (N = 34) viewed four film clips inducing anger, happiness, fear, or no emotion, and completed the IPANAT and the Positive And Negative Affect Scale at baseline and after each clip. Implicit negative affect (INA) was higher and implicit positive affect (IPA) was lower after the anger inducing clip and vice versa after the happiness inducing clip. In Study 2 students performed a stressful math task with (n = 14) or without anger harassment (n = 15) and completed the IPANAT and a Visual Analog Scale as an explicit measure afterwards. Systolic (SBP), diastolic (DBP) blood pressure, heart rate (HR), heart rate variability (HRV), and total peripheral resistance (TPR) were recorded throughout. SBP and DBP were higher and TPR was lower in the harassment condition during the task with a prolonged effect on SBP and DBP during recovery. As expected, explicit negative affect (ENA) was higher and explicit positive affect (EPA) lower after harassment, but ENA and EPA were not related to CV activity. Although neither INA nor IPA differed between the tasks, during both tasks higher INA was related to higher SBP, lower HRV and lower TPR and to slower recovery of DBP after both tasks. Low IPA was related to slower recovery of SBP and DBP after the tasks. Implicit affect was not related to recovery of HR, HRV, and TPR. In conclusion, the IPANAT seems to respond to film clip-induced negative and positive affect and was related to CV activity during and after stressful tasks. These findings support the theory that implicitly measured affect can add to the explanation of prolonged stress-related CV responses that influence CV health.

Role of negative emotion in communication about CO2 risks.

PubMed

Meijnders, A L; Midden, C J; Wilke, H A

2001-10-01

This article describes how the effectiveness of risk communication is determined by the interaction between emotional and informative elements. An experiment is described that examined the role of negative emotion in communication about CO2 risks. This experiment was based on the elaboration likelihood model and the related heuristic systematic model of attitude formation. The results indicated that inducing fear of CO2 risks leads to systematic processing of information about energy conservation as a risk-reducing strategy. In turn, this results in more favorable attitudes toward energy conservation if strong arguments are provided. Individual differences in concern seem to have similar effects.

Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer

PubMed Central

King, Suzanne N.; Dunlap, Neal E.; Tennant, Paul A.; Pitts, Teresa

2017-01-01

Oncologic treatments, such as curative radiotherapy and chemoradiation, for head and neck cancer can cause long-term swallowing impairments (dysphagia) that negatively impact quality of life. Radiation-induced dysphagia is comprised of a broad spectrum of structural, mechanical, and neurologic deficits. An understanding of the biomolecular effects of radiation on the time course of wound healing and underlying morphological tissue responses that precede radiation damage will improve options available for dysphagia treatment. The goal of this review is to discuss the pathophysiology of radiation-induced injury and elucidate areas that need further exploration. PMID:27098922

Stress-evoked opioid release inhibits pain in major depressive disorder.

PubMed

Frew, Ashley K; Drummond, Peter D

2008-10-15

To determine whether stress-evoked release of endogenous opioids might account for hypoalgesia in major depressive disorder (MDD), the mu-opioid antagonist naltrexone (50mg) or placebo was administered double-blind to 24 participants with MDD and to 31 non-depressed controls. Eighty minutes later participants completed a painful foot cold pressor test and, after a 5-min interval, began a 25-min arithmetic task interspersed with painful electric shocks. Ten minutes later participants completed a second cold pressor test. Negative affect was greater in participants with MDD than in non-depressed controls throughout the experiment, and increased significantly in both groups during mental arithmetic. Before the math task, naltrexone unmasked direct linear relationships between severity of depression, negative affect while resting quietly, and cold-induced pain in participants with MDD. In contrast, facilitatory effects of naltrexone on cold- and shock-induced pain were greatest in controls with the lowest depression scores. Naltrexone strengthened the relationship between negative affect and shock-induced pain during the math task, particularly in the depressed group, and heightened anxiety in both groups toward the end of the task. Thus, mu-opioid activity apparently masked a positive association between negative affect and pain in the most distressed participants. These findings suggest that psychological distress inhibits pain via stress-evoked release of opioid peptides in severe cases of MDD. In addition, tonic endogenous opioid neurotransmission could inhibit depressive symptoms and pain in people with low depression scores.

Protocol of a randomized controlled trial of hearing protection interventions for farm operators.

PubMed

McCullagh, Marjorie C; Ronis, David L

2015-04-18

Hearing loss and tinnitus are prevalent in America, and noise-induced hearing loss is a leading cause of hearing loss. Noise-induced hearing loss has negative impact on quality of life, physical and emotional functioning, social life, and employment. In addition, noise-induced hearing loss results in heavy social and economic burdens on families and communities from all ethnic and socioeconomic groups. Farmers are a group that is particularly high risk for noise-induced hearing loss, and is underserved by programs designed to limit that risk. They are among the most noise-exposed group of workers, and experience the second highest prevalence of noise-induced hearing loss among all occupational categories. In agriculture, 1.5 million workers (43.3%) report exposure to hazardous noise. Although use of hearing protection devices (HPDs) would protect them from noise-induced hearing loss, use among farmers is low. The purpose of this project is to compare the effectiveness of several approaches to influencing hearing protector use. Approaches include: a) an interactive, predictors-based intervention delivered via the Internet; b) a static informational web site; and c) a mailed sampler of hearing protectors. The goals are to further develop an intervention to promote farmers' use of HPDs, and compare the effectiveness of the interventions delivered in various combinations. Participants will include 701 farmers. Sites will be affiliates of a major farmer organization. Data will be collected at baseline, 6, and 12 months. A random intercept mixed model will be used to explore the fixed effects of the three NIHL prevention interventions over time while adjusting for age and gender. This project will involve a partnership between the University of Michigan and a major farmer organization to accomplish project aims. Results of this study will be used to inform future research-to-practice studies to increase hearing protector use. Increased use of hearing protectors is expected to reduce rates of noise-induced hearing loss and other negative effects of high noise exposure, and improve quality of life in this high-risk and underserved group. Clinicaltrials.gov NCT01454895 Registered 14 October, 2011.

Effect of Mood States on the Breadth of Spatial Attentional Focus: An Event-Related Potential Study

ERIC Educational Resources Information Center

Moriya, Hiroki; Nittono, Hiroshi

2011-01-01

In order to determine the processing stage that is responsible for the effect of mood states on the breadth of attentional focus, we recorded event-related potentials from 18 students who performed a flanker task involving adjacent letters. To induce a specific mood state, positive, neutral, or negative affective pictures were presented repeatedly…

Interactive Effects of Jasmonic Acid, Salicylic Acid, and Gibberellin on Induction of Trichomes in Arabidopsis1

PubMed Central

Traw, M. Brian; Bergelson, Joy

2003-01-01

Leaf trichomes protect plants from attack by insect herbivores and are often induced following damage. Hormonal regulation of this plant induction response has not been previously studied. In a series of experiments, we addressed the effects of artificial damage, jasmonic acid, salicylic acid, and gibberellin on induction of trichomes in Arabidopsis. Artificial damage and jasmonic acid caused significant increases in trichome production of leaves. The jar1-1 mutant exhibited normal trichome induction following treatment with jasmonic acid, suggesting that adenylation of jasmonic acid is not necessary. Salicylic acid had a negative effect on trichome production and consistently reduced the effect of jasmonic acid, suggesting negative cross-talk between the jasmonate and salicylate-dependent defense pathways. Interestingly, the effect of salicylic acid persisted in the nim1-1 mutant, suggesting that the Npr1/Nim1 gene is not downstream of salicylic acid in the negative regulation of trichome production. Last, we found that gibberellin and jasmonic acid had a synergistic effect on the induction of trichomes, suggesting important interactions between these two compounds. PMID:14551332

A comparative study on the effect of Curcumin and Chlorin-p6 on the diffusion of two organic cations across a negatively charged lipid bilayer probed by second harmonic spectroscopy

NASA Astrophysics Data System (ADS)

Saini, R. K.; Varshney, G. K.; Dube, A.; Gupta, P. K.; Das, K.

2014-09-01

The influence of Curcumin and Chlorin-p6 (Cp6) on the real time diffusion kinetics of two organic cations, LDS (LDS-698) and Malachite Green (MG) across a negatively charged phospholipid bilayer is investigated by Second Harmonic (SH) spectroscopy. The diffusion time constant of LDS at neutral pH in liposomes containing either Curcumin or Cp6 is significantly reduced, the effect being more pronounced with Curcumin. At acidic pH, the quantum of reduction in the diffusion time constant of MG by both the drugs was observed to be similar. The relative changes in the average diffusion time constants of the cations with increasing drug concentration at pH 5.0 and 7.4 shows a substantial pH effect for Curcumin induced membrane permeability, while a modest pH effect was observed for Cp6 induced membrane permeability. Based on available evidence this can be attributed to the increased interaction between the drug and the polar head groups of the lipid at pH 7.4 where the drug resides closer to the lipid-water interface.

How the Brain Converts Negative Evaluation into Performance Facilitation.

PubMed

Prévost, Charlotte; Lau, Hakwan; Mobbs, Dean

2018-02-01

Surpassing negative evaluation is a recurrent theme of success stories. Yet, there is little evidence supporting the counterintuitive idea that negative evaluation might not only motivate people, but also enhance performance. To address this question, we designed a task that required participants to decide whether taking up a risky challenge after receiving positive or negative evaluations from independent judges. Participants believed that these evaluations were based on their prior performance on a related task. Results showed that negative evaluation caused a facilitation in performance. Concurrent functional magnetic resonance imaging revealed that the motivating effect of negative evaluation was represented in the insula and striatum, while the performance boost was associated with functional positive connectivity between the insula and a set of brain regions involved in goal-directed behavior and the orienting of attention. These findings provide new insight into the neural representation of negative evaluation-induced facilitation. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Impact of Positive and Negative Affect and Issue Framing on Issue Interpretation and Risk Taking.

PubMed

Mittal; Ross

1998-12-01

Two studies examined the influence of transient affective states and issue framing on issue interpretation and risk taking within the context of strategic decision making. In Study 1, participants in whom transient positive or negative affective states were induced by reading a short story showed systematic differences in issue interpretation and risk taking in a strategic decision making context. Compared to negative mood participants, those in a positive mood were more likely to interpret the strategic issue as an opportunity and displayed lower levels of risk taking. Study 2 replicated and extended these results by crossing affective states with threat and opportunity frames. Results showed that framing an issue (as a threat or an opportunity) had a stronger impact on issue interpretation among negative affect participants than among positive affect participants. Affective states also moderated the impact of issue framing on risk taking: the effect of framing on risk-taking was stronger under negative rather than positive affect. These results are interpreted via information-processing and motivational effects of affect on a decision maker. Copyright 1998 Academic Press.

Priming effects under correct change detection and change blindness.

PubMed

Caudek, Corrado; Domini, Fulvio

2013-03-01

In three experiments, we investigated the priming effects induced by an image change on a successive animate/inanimate decision task. We studied both perceptual (Experiments 1 and 2) and conceptual (Experiment 3) priming effects, under correct change detection and change blindness (CB). Under correct change detection, we found larger positive priming effects on congruent trials for probes representing animate entities than for probes representing artifactual objects. Under CB, we found performance impairment relative to a "no-change" baseline condition. This inhibition effect induced by CB was modulated by the semantic congruency between the changed item and the probe in the case of probe images, but not for probe words. We discuss our results in the context of the literature on the negative priming effect. Copyright © 2012 Elsevier Inc. All rights reserved.

Tetraspanin 6 (TSPAN6) Negatively Regulates Retinoic Acid-inducible Gene I-like Receptor-mediated Immune Signaling in a Ubiquitination-dependent Manner*

PubMed Central

Wang, Yetao; Tong, Xiaomei; Omoregie, Ehimwenma Sheena; Liu, Wenjun; Meng, Songdong; Ye, Xin

2012-01-01

The recognition between retinoic acid-inducible gene I-like receptors (RLRs) and viral RNA triggers an intracellular cascade of signaling to induce the expression of type I IFNs. Both positive and negative regulation of the RLR signaling pathway are important for the host antiviral immune response. Here, we demonstrate that the tetraspanin protein TSPAN6 inhibits RLR signaling by affecting the formation of the adaptor MAVS (mitochondrial antiviral signaling)-centered signalosome. We found that overexpression of TSPAN6 impaired RLR-mediated activation of IFN-stimulated response element, NF-κB, and IFN-β promoters, whereas knockdown of TSPAN6 enhanced the RLR-mediated signaling pathway. Interestingly, as the RLR pathway was activated, TSPAN6 underwent Lys-63-linked ubiquitination, which promoted its association with MAVS. The interaction of TSPAN6 and MAVS interfered with the recruitment of RLR downstream molecules TRAF3, MITA, and IRF3 to MAVS. Further study revealed that the first transmembrane domain of TSPAN6 is critical for its ubiquitination and association with MAVS as well as its inhibitory effect on RLR signaling. We concluded that TSPAN6 functions as a negative regulator of the RLR pathway by interacting with MAVS in a ubiquitination-dependent manner. PMID:22908223

Effects of worry on physiological and subjective reactivity to emotional stimuli in generalized anxiety disorder and nonanxious control participants.

PubMed

Llera, Sandra J; Newman, Michelle G

2010-10-01

The present study examined the effect of worry versus relaxation and neutral thought activity on both physiological and subjective responding to positive and negative emotional stimuli. Thirty-eight participants with generalized anxiety disorder (GAD) and 35 nonanxious control participants were randomly assigned to engage in worry, relaxation, or neutral inductions prior to sequential exposure to each of four emotion-inducing film clips. The clips were designed to elicit fear, sadness, happiness, and calm emotions. Self reported negative and positive affect was assessed following each induction and exposure, and vagal activity was measured throughout. Results indicate that worry (vs. relaxation) led to reduced vagal tone for the GAD group, as well as higher negative affect levels for both groups. Additionally, prior worry resulted in less physiological and subjective responding to the fearful film clip, and reduced negative affect in response to the sad clip. This suggests that worry may facilitate avoidance of processing negative emotions by way of preventing a negative emotional contrast. Implications for the role of worry in emotion avoidance are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

An Investigation on the Effects of Different Stratifications on Negatively Buoyant Jets

NASA Astrophysics Data System (ADS)

Ferrari, Simone; Badas, Maria Grazia; Querzoli, Giorgio

2018-06-01

Negatively buoyant jets develop when fluids are released upwards into a lighter fluid or, vice versa, downwards into a heavier fluid. There are many engineering applications, such as the discharge, via submerged outfalls, of brine from desalination plants into the sea. Some concerns are raised about the potential negative environmental impacts of this discharge. The increase in salinity is the major cause for environmental impact, as it is very harmful to many marine species. The diffusers for brine discharge are typically inclined upwards, to increase the path before the brine reaches the sea bottom, as it tends to fall downwards driven by negative buoyancy. The negatively buoyant jet that develops conserves axisymmetry only when released vertically, so that it is not possible to use the well-known equations for axisymmetric jets. The main target of this paper is to investigate on a laboratory model the effects of different stratifications on the features of negatively buoyant jets. This has been done via a LIF (Light Induced Fluorescence) technique, testing various release angles on the horizontal and densimetric Froude numbers. Except for the initial stage, a different widening rate for the upper boundary and the lower boundary has been highlighted.

Protective effect of D-002, a mixture of beeswax alcohols, against indomethacin-induced gastric ulcers and mechanism of action.

PubMed

Pérez, Yohani; Oyárzabal, Ambar; Mas, Rosa; Molina, Vivian; Jiménez, Sonia

2013-01-01

D-002, a mixture of higher aliphatic beeswax alcohols, produces gastroprotective and antioxidant effects. To investigate the gastroprotective effect of D-002 against indomethacin-induced ulcers, oxidative variables and myeloperoxidase (MPO) activity in the rat gastric mucosa were examined. Rats were randomized into six groups: a negative vehicle control and five indomethacin (50 mg/kg) treated groups, comprising a positive control, three groups treated orally with D-002 (5, 25 and 100 mg/kg) and one group with omeprazole 20 mg/kg intraperitoneally (ip). The contents of malondialdehyde (MDA), protein carbonyl groups (PCG), hydroxyl radical generation and catalase (CAT), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and MPO enzyme activities in the rat gastric mucosa were assessed. Indomethacin increased the content of MDA and PCG, the generation of *OH radical and MPO enzyme activity, while it decreased the CAT, GSH-PX and SOD activities as compared to the negative controls. D-002 (5-100 mg/kg) significantly and dose-dependently reduced indomethacin-induced ulceration to 75 %. Also, D-002 decreased the content of MDA and PCG, the generation of hydroxyl radicals and MPO activity as compared to the positive controls. The highest dose of D-002 (100 mg/kg) increased significantly GSH-PX and SOD activities, while all doses used increased CAT activities. Omeprazole 20 mg/kg, the reference drug, reduced significantly the ulcers (93 %), MDA and PCG, the generation of hydroxyl radicals and MPO activity, and increased the CAT, GSH-PX and SOD activities. D-002 treatment produced gastroprotective effects against indomethacin-induced gastric ulceration, which can be related to the reduction of hydroxyl radical generation, lipid peroxidation, protein oxidation and MPO activity, and to the increase of the antioxidant enzymes activities in the rat gastric mucosa.

Resveratrol reverses the adverse effects of a diet-induced obese murine model on oocyte quality and zona pellucida softening.

PubMed

Jia, Zhenzhen; Feng, Zeyang; Wang, Lining; Li, Hao; Wang, Hongyu; Xu, Dingqi; Zhao, Xin; Feng, Daofu; Feng, Xizeng

2018-05-23

Reproductive dysfunction associated with obesity is increasing among women of reproductive age, including infertility and increasing risk of miscarriage. In females, reproductive disorders are linked to declining quality of oocytes. Using a model of diet-induced obesity, we have investigated the possible effects of obesity on oocyte quality, including metabolism, lipid accumulation, ROS levels, meiosis and changes in spindle structure in Metaphase II. Our study showed that obesity induced by a high fat diet can impair oocyte meiosis, destroy spindle assembly, and promote oxidative stress and abnormal mitochondrial distribution. With the addition of resveratrol, the negative impact of diet-induced obesity on the quality of oocytes was alleviated to some extent. In addition, we found that obesity causes mouse oocytes to soften, and resveratrol can restore the zona pellucida of oocytes to the same state as the control group. In conclusion, resveratrol can reverse the adverse effects of obesity on oocytes, which is beneficial for subsequent embryonic development.

Sex differences in the acute locomotor response to methamphetamine in BALB/c mice.

PubMed

Ohia-Nwoko, Odochi; Haile, Colin N; Kosten, Therese A

2017-06-01

Women use methamphetamine more frequently than men and are more vulnerable to its negative psychological effects. Rodent models have been an essential tool for evaluating the sex-dependent effects of psychostimulants; however, evidence of sex differences in the behavioral responses to methamphetamine in mice is lacking. In the present study, we investigated acute methamphetamine-induced (1mg/kg and 4mg/kg) locomotor activation in female and male BALB/c mice. We also evaluated whether basal locomotor activity was associated with the methamphetamine-induced locomotor response. The results indicated that female BALB/c mice displayed enhanced methamphetamine-induced locomotor activity compared to males, while basal locomotor activity was positively correlated with methamphetamine-induced activity in males, but not females. This study is the first to show sex-dependent locomotor effects of methamphetamine in BALB/c mice. Our observations emphasize the importance of considering sex when assessing behavioral responses to methamphetamine. Copyright © 2017 Elsevier B.V. All rights reserved.

Sex differences in negative affect and lapse behavior during acute tobacco abstinence: a laboratory study.

PubMed

Pang, Raina D; Leventhal, Adam M

2013-08-01

Heightened negative affect during acute tobacco abstinence in women relative to men could be an important factor underlying sex differences in smoking motivation. However, little controlled experimental work addresses this hypothesis. The current study investigated sex differences in withdrawal-related negative affect, time to start smoking on a lab analogue smoking lapse task, and the interrelation between sex, withdrawal-related negative affect, and smoking lapse behavior. Following a baseline session, current smokers (women: n = 68, men: n = 131) attended two counterbalanced lab sessions (16 hours smoking abstinence and ad libitum smoking) during which they completed self-report measures of mood and withdrawal symptoms followed by a laboratory analogue smoking lapse task. In this task participants are monetarily rewarded for delaying smoking. Performance on this task serves as an analogue model of smoking lapse behavior by measuring smoker's capability to resist temptation to smoke under conditions where abstinence is advantageous. Females showed greater abstinence induced increases in composite negative affect as well as several particular negative affect states (i.e., POMS Anger, Anxiety, Depression, and Confusion, ps < .05) but no differences in abstinence induced changes in other forms of affect or craving. Females also exhibited marginally greater abstinence induced decreases in their willingness to delay smoking for money (p = .10), which was mediated by abstinence induced increases in anger (p < .05). These results suggest that differential sensitivity to abstinence induced negative affect, particularly anger, could underlie sex specific smoking patterns. Negative affect during tobacco abstinence may be an important factor for understanding and treating nicotine addiction in women. PsycINFO Database Record (c) 2013 APA, all rights reserved

Negative modulation of α5 GABAA receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion

PubMed Central

Stamenić, Tamara Timić; Joksimović, Srdjan; Biawat, Poonam; Stanković, Tamara; Marković, Bojan; Cook, James M; Savić, Miroslav M

2016-01-01

Reportedly, negative modulation of α5 GABAA receptors may improve cognition in normal and pharmacologically-impaired animals, and such modulation has been proposed as an avenue for treatment of cognitive symptoms in schizophrenia. This study assessed the actions of PWZ-029, administered at doses (2, 5 and 10 mg/kg) at which it reached micromolar concentrations in brain tissue with estimated free concentrations adequate for selective modulation of α5 GABAA receptors, in three cognitive tasks in male Wistar rats acutely treated with the noncompetitive N-methyl-D-aspartate – receptor antagonist, MK-801 (0.1 mg/kg), as well in tests of locomotor activity potentiated by MK-801 (0.2 mg/kg) or amphetamine (0.5 mg/kg). In a hormetic-like manner, only 5 mg/kg PWZ-029 reversed MK-801-induced deficits in novel object recognition test (visual recognition memory), whereas in the Morris water maze, the 2 mg/kg dose of PWZ-029 exerted partial beneficial effects on spatial learning impairment. PWZ-029 did not affect recognition memory deficits in social novelty discrimination procedure. Motor hyperactivity induced with MK-801 or amphetamine was not preventable by PWZ-029. Our results show that certain MK-801-induced memory deficits can be ameliorated by negative modulation of α5 GABAA receptors, and point to the need for further elucidation of their translational relevance to cognitive deterioration in schizophrenia. PMID:26105958

Negative modulation of α₅ GABAA receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion.

PubMed

Timić Stamenić, Tamara; Joksimović, Srdjan; Biawat, Poonam; Stanković, Tamara; Marković, Bojan; Cook, James M; Savić, Miroslav M

2015-09-01

Reportedly, negative modulation of α5 GABAA receptors may improve cognition in normal and pharmacologically-impaired animals, and such modulation has been proposed as an avenue for treatment of cognitive symptoms in schizophrenia. This study assessed the actions of PWZ-029, administered at doses (2, 5, and 10 mg/kg) at which it reached micromolar concentrations in brain tissue with estimated free concentrations adequate for selective modulation of α5 GABAA receptors, in three cognitive tasks in male Wistar rats acutely treated with the noncompetitive N-methyl-d-aspartate receptor antagonist, MK-801 (0.1 mg/kg), as well in tests of locomotor activity potentiated by MK-801 (0.2 mg/kg) or amphetamine (0.5 mg/kg). In a hormetic-like manner, only 5 mg/kg PWZ-029 reversed MK-801-induced deficits in novel object recognition test (visual recognition memory), whereas in the Morris water maze, the 2 mg/kg dose of PWZ-029 exerted partial beneficial effects on spatial learning impairment. PWZ-029 did not affect recognition memory deficits in social novelty discrimination procedure. Motor hyperactivity induced with MK-801 or amphetamine was not preventable by PWZ-029. Our results show that certain MK-801-induced memory deficits can be ameliorated by negative modulation of α5 GABAA receptors, and point to the need for further elucidation of their translational relevance to cognitive deterioration in schizophrenia. © The Author(s) 2015.

Thermally-Induced Structural Disturbances of Rigid Panel Solar Arrays

NASA Technical Reports Server (NTRS)

Johnston, John D.; Thornton, Earl A.

1997-01-01

The performance of a significant number of spacecraft has been impacted negatively by attitude disturbances resulting from thermally-induced motions of flexible structures. Recent examples of spacecraft affected by these disturbances include the Hubble Space Telescope (HST) and the Upper Atmosphere Research Satellite (UARS). Thermally-induced structural disturbances occur as the result of rapid changes in thermal loading typically initiated as a satellite exits or enters the Earth's shadow. Temperature differences in flexible appendages give rise to structural deformations, which in turn result in disturbance torques reacting back on the spacecraft. Structures which have proven susceptible to these disturbances include deployable booms and solar arrays. This paper investigates disturbances resulting from thermally-induced deformations of rigid panel solar arrays. An analytical model for the thermal-structural response of the solar array and the corresponding disturbance torque are presented. The effect of these disturbances on the attitude dynamics of a simple spacecraft is then investigated using a coupled system of governing equations which includes the effects of thermally-induced deformations. Numerical results demonstrate the effect of varying solar array geometry on the dynamic response of the system.

Sea-ice induced growth decline in Arctic shrubs.

PubMed

Forchhammer, Mads

2017-08-01

Measures of increased tundra plant productivity have been associated with the accelerating retreat of the Arctic sea-ice. Emerging studies document opposite effects, advocating for a more complex relationship between the shrinking sea-ice and terrestrial plant productivity. I introduce an autoregressive plant growth model integrating effects of biological and climatic conditions for analysing individual ring-width growth time series. Using 128 specimens of Salix arctica , S. glauca and Betula nana sampled across Greenland to Svalbard, an overall negative effect of the retreating June sea-ice extent was found on the annual growth. The negative effect of the retreating June sea-ice was observed for younger individuals with large annual growth allocations and with little or no trade-off between previous and current year's growth. © 2017 The Author(s).

Cluster synchronization induced by one-node clusters in networks with asymmetric negative couplings

NASA Astrophysics Data System (ADS)

Zhang, Jianbao; Ma, Zhongjun; Zhang, Gang

2013-12-01

This paper deals with the problem of cluster synchronization in networks with asymmetric negative couplings. By decomposing the coupling matrix into three matrices, and employing Lyapunov function method, sufficient conditions are derived for cluster synchronization. The conditions show that the couplings of multi-node clusters from one-node clusters have beneficial effects on cluster synchronization. Based on the effects of the one-node clusters, an effective and universal control scheme is put forward for the first time. The obtained results may help us better understand the relation between cluster synchronization and cluster structures of the networks. The validity of the control scheme is confirmed through two numerical simulations, in a network with no cluster structure and in a scale-free network.

The effect of combined treatment with risperidone and antidepressants on the MK-801-induced deficits in the social interaction test in rats.

PubMed

Kamińska, Katarzyna; Rogóż, Zofia

2015-12-01

Several clinical reports have suggested that augmentation of atypical antipsychotics' activity by antidepressants may efficiently improve the treatment of negative and some cognitive symptoms of schizophrenia. The aim of the present study was to investigate the effect of antidepressant mirtazapine or escitalopram and risperidone (an atypical antipsychotic), given separately or jointly, on the MK-801-induced deficits in the social interaction test in rats. Antidepressants and risperidone were given 60 and 30 min before the test, respectively. The social interaction of male Wistar rats was measured for 10 min, starting 4 h after MK-801 (0.1 mg/kg) administration. In the social interaction test, MK-801-induced deficits in the parameters studied, i.e. the number of episodes and the time of interactions. Risperidone at a higher dose (0.1 mg/kg) reversed that effect. Co-treatment with an ineffective dose of risperidone (0.01 mg/kg) and mirtazapine (2.5 or 5 mg/kg) or escitalopram only at a dose of 5 mg/kg (but not 2.5 and 10 mg/kg) abolished the deficits evoked by MK-801. The obtained results suggest that especially mirtazapine, and to a smaller degree escitalopram may enhance the antipsychotic-like effect of risperidone in the animal test modeling some negative symptoms of schizophrenia. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The efficacy and safety of irsogladine maleate in nonsteroidal anti-inflammatory drug or aspirin-induced peptic ulcer and gastritis.

PubMed

Shim, Ki-Nam; Kim, Jin Il; Kim, Nayoung; Kim, Sang Gyun; Jo, Yun Ju; Hong, Su Jin; Shin, Jeong Eun; Kim, Gwang Ha; Park, Kyung Sik; Choi, Suck Chei; Kwon, Joong Goo; Kim, Jie-Hyun; Kim, Hyun Jin; Kim, Ji Won

2018-06-01

Irsogladine maleate, an enhancer of gastric mucosal protective factors, has demonstrated its efficacy for various gastric mucosal injuries. The aim of this study was to evaluate the efficacy and safety of irsogladine for prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin-induced peptic ulcer and gastritis. In this multicenter, randomized, double-blind, exploratory clinical trial, 100 patients over 50 years of age who needed continuous NSAIDs or aspirin for more than 8 weeks were randomly assigned to either test group (irsogladine maleate 2 mg, twice daily, 39 patients for full analysis) or placebo group (37 patients for full analysis). Primary outcomes were incidence of peptic ulcer and ratio of modified Lanza score (MLS) 2 to 4. Secondary outcome was the number of acute erosions confirmed by endoscopy at 8 weeks. Adverse effects were also compared. There were no significant differences in gastric protective effects between test and placebo groups. However, two cases of peptic ulcer in the placebo group but none in the test group were observed. These two cases of peptic ulcer were Helicobacter pylori-negative. In addition, H. pylori-negative group showed significant changes in MLS score (p = 0.0247) and edema score (p = 0.0154) after the treatment compared to those before treatment in the test group. There was no significant difference in adverse events between the two groups. The efficacy of irsogladine maleate was found in H. pylori-negative group, suggesting its potential as a protective agent against NSAIDs or aspirin-induced peptic ulcer and gastritis.

Can repetitive mental simulation of smoking engender habituation?

PubMed Central

Audrain-McGovern, Janet; Strasser, Andrew A.; Wileyto, E. Paul

2016-01-01

Smoking cue exposure sensitizes smokers to cigarettes (i.e., increases cravings). Research examining the overlap between perception and mental imagery suggests that mentally simulating smoking a cigarette in a manner analogous to actually smoking should lead to habituation or a decrease in a smoker’s motivation to smoke. We sought to determine whether repetitive mental simulation of smoking can engender habituation thereby reducing smoking cue-induced craving and shifts in mood, latency to smoke, and the hedonic response to smoking. These hypotheses were tested in non-treatment seeking smokers (n=61; 24 female/ 37male) ages 18–55 years old, who were not incentivized to quit. We used a 2 (In Vivo Cue: Smoking, Neutral) x 2 (Imagery: Repetitive, Limited) within-subjects design. Results revealed that repetitive imagery altered the effect of cue type for negative mood and subjective cigarette reward as evidenced by significant imagery x cue interactions. Repetitive imagery after a smoking cue reduced negative mood more than limited imagery (β = −1.19, p = .004). Repetitive imagery also reduced the reward derived from smoking a cigarette more than limited imagery (β = −.41, p < .0001). Only main effects of cue type on craving (β = 3.39, p = .01) and positive mood (β = −1.18, p = .03) were found. Greater imagery strength predicted a longer latency to smoke (β = .76, p = .001). Cognitive strategies that directly engage cue-induced craving through repetitive smoking imagery may reduce smoking cue-induced increases in negative mood and reward from a cigarette lapse potentially preventing smoking relapse. PMID:27929344

Melatonin protects chondrocytes from impairment induced by glucocorticoids via NAD+-dependent SIRT1.

PubMed

Yang, Wei; Kang, Xiaomin; Qin, Na; Li, Feng; Jin, Xinxin; Ma, Zhengmin; Qian, Zhuang; Wu, Shufang

2017-10-01

Intra-articular injection of glucocorticoids is used to relieve pain and inflammation in osteoarthritis patients, which is occasionally accompanied with the serious side effects of glucocorticoids in collagen-producing tissue. Melatonin is the major hormone released from the pineal gland and its beneficial effects on cartilage has been suggested. In the present study, we investigated the protective role of melatonin on matrix degeneration in chondrocytes induced by dexamethasone (Dex). The chondrocytes isolated from mice knee joint were treated with Dex, melatonin, EX527 and siRNA targeted for SIRT6, respectively. Dex treatment induced the loss of the extracellular matrix, NAD + /NADH ratio and NADPH concentration in chondrocytes. Melatonin alone have no effect on the quantity of proteoglycans and collagen type IIa1, however, the pretreatment of melatonin reversed the negative effects induced by Dex. Meanwhile, the significant decrease in NAD + /NADH ratio and NADPH concentration in Dex group were up-regulated by pretreatment of melatonin. Furthermore, it was revealed that inhibition of SIRT1 blocked the protective effects of melatonin. The enhancement of NAD + -dependent SIRT1 activity contributes to the chondroprotecfive effects of melatonin, which has a great benefit to prevent dexamethasone-induced chondrocytes impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of pyrogenic organic matter decomposition and induced priming effect on soil C budget.

NASA Astrophysics Data System (ADS)

Maestrini, Bernardo; Abiven, Samuel

2014-05-01

Pyrogenic organic matter (PyOM) results from the incomplete combustion of biomass and may contribute to constitute an important fraction of soil C in forest and agricultural soils, in the form of charcoal (produced by wildfires) or biochar (anthropogenic). Although many evidences exist on the long mean residence time of PyOM there is still a large uncertainty on PyOM loss processes and rate and on possible induced priming effect on non-PyOM. Therefore determining PyOM mineralization rate, loss processes and possible induced priming effect on soil organic matter decomposition are key issues to understand the impact of PyOM on the carbon (C) cycle. We investigated the impact of PyOM on soil C budget by combining results from three independent studies: (i) a field study to investigate PyOM mineralization rate and the relative importance of PyOM loss processes, (ii) a PyOM and soil incubation experiment to correlate C and N mineralization rates, (iii) a review of the priming effect induced by PyOM on soil organic C. We employed 13C labelled pinewood-derived PyOM for the field experiment and 13C labelled ryegrass-derived PyOM in the incubation experiment to trace PyOM losses. In the field experiment it was observed that: (i) Pyrolysis process reduced pinewood decomposition by a factor of 60, (ii) leaching and translocation of fresh PyOM along the soil profile were negligible compared to losses as CO2. In the incubation experiment we found that ryegrass induced a two phase priming effect on native soil organic matter, with a positive priming effect followed by a negative priming effect phase, we also found that ryegrass-derived PyOM decomposition was much slower than pinewood one. The different decomposition rate results probably from the different aromaticity of the two PyOM together with the different set-up of the two experiments. Both the incubation experiment and the meta-analysis revealed that PyOM may induce a two-phase priming effect on native soil organic matter decomposition: positive on the short term and negative on the long term. The meta-analysis showed that that positive priming effect is induced mostly on the native soil organic matter on the short term and by PyOM characterised by a low C content. This result was not confirmed on the freshly added organic matter. We believe that the presence of a labile fraction in PyOM may induce positive priming effect on the short term by mean of co-metabolism. We conclude that PyOM chemical composition and feedstock play an important role in predicting PyOM mineralization rate, and that on the short term PyOM may induce a positive priming effect therefore decreasing the abatement potential of PyOM as a C-sink.

Genotoxicity induced by monomethylarsonous acid (MMA+3) in mouse thymic developing T cells.

PubMed

Xu, Huan; Medina, Sebastian; Lauer, Fredine T; Douillet, Christelle; Liu, Ke Jian; Stýblo, Miroslav; Burchiel, Scott W

2017-09-05

Drinking water exposure to arsenic is known to cause immunotoxicity. Our previous studies demonstrated that monomethylarsonous acid (MMA +3 ) was the major arsenical species presented in mouse thymus cells after a 30 d drinking water exposure to arsenite (As +3 ). MMA +3 was also showed to be ten times more toxic than As +3 on the suppression of IL-7/STAT5 signaling in the double negative (DN) thymic T cells. In order to examine the genotoxicity induced by low to moderate doses of MMA +3 , isolated mouse thymus cells were treated with 5, 50 and 500nMMMA +3 for 18h in vitro. MMA +3 suppressed the proliferation of thymus cells in a dose dependent manner. MMA +3 at 5nM induced DNA damage in DN not double positive (DP) cells. Differential sensitivity to double strand breaks and reactive oxygen species generation was noticed between DN and DP cells at 50nM, but the effects were not seen at the high dose (500nM). A stronger apoptotic effect induced by MMA +3 was noticed in DN cells than DP cells at low doses (5 and 50nM), which was negated by the strong apoptosis induction at the high dose (500nM). Analysis of intracellular MMA +3 concentrations in DN and DP cells, revealed that more MMA +3 accumulated in the DN cells after the in vitro treatment. Collectively, these results suggested that MMA +3 could directly induce strong genotoxicity in the early developing T cells in the thymus. The DN cells were much more sensitive to MMA +3 induced genotoxicity and apoptosis than DP cells, probably due to the higher intracellular levels of MMA +3 . Copyright © 2017 Elsevier B.V. All rights reserved.

Epidermal Phytochrome B Inhibits Hypocotyl Negative Gravitropism Non-Cell-Autonomously.

PubMed

Kim, Jaewook; Song, Kijong; Park, Eunae; Kim, Keunhwa; Bae, Gabyong; Choi, Giltsu

2016-11-01

Seedling hypocotyls display negative gravitropism in the dark but agravitropism in the light. The Arabidopsis thaliana pif quadruple mutant (pifQ), which lacks four PHYTOCHROME-INTERACTING FACTORS (PIFs), is agravitropic in the dark. Endodermis-specific expression of PIF1 rescues gravitropism in pifQ mutant seedlings. Since phytochromes induce light responses by inhibiting PIFs and the COP1-SPA ubiquitin E3 ligase complex in the nucleus, we asked whether phyB can cell autonomously inhibit hypocotyl negative gravitropism in the endodermis. We found that while epidermis-specific expression of PHYB rescues hypocotyl negative gravitropism and all other phyB mutant phenotypes, endodermis-specific expression of PHYB does not. Epidermal phyB induces the phosphorylation and degradation of endodermal PIFs in response to red light. This induces a global gene expression pattern similar to that induced by red light treatment of seedlings expressing PHYB under the control of its own endogenous promoter. Our results imply that epidermal phyB generates an unidentified mobile signal that travels to the endodermis where it promotes PIF degradation and inhibits hypocotyl negative gravitropism. © 2016 American Society of Plant Biologists. All rights reserved.

Epidermal Phytochrome B Inhibits Hypocotyl Negative Gravitropism Non-Cell-Autonomously

PubMed Central

Kim, Jaewook; Song, Kijong; Park, Eunae; Kim, Keunhwa; Choi, Giltsu

2016-01-01

Seedling hypocotyls display negative gravitropism in the dark but agravitropism in the light. The Arabidopsis thaliana pif quadruple mutant (pifQ), which lacks four PHYTOCHROME-INTERACTING FACTORS (PIFs), is agravitropic in the dark. Endodermis-specific expression of PIF1 rescues gravitropism in pifQ mutant seedlings. Since phytochromes induce light responses by inhibiting PIFs and the COP1-SPA ubiquitin E3 ligase complex in the nucleus, we asked whether phyB can cell autonomously inhibit hypocotyl negative gravitropism in the endodermis. We found that while epidermis-specific expression of PHYB rescues hypocotyl negative gravitropism and all other phyB mutant phenotypes, endodermis-specific expression of PHYB does not. Epidermal phyB induces the phosphorylation and degradation of endodermal PIFs in response to red light. This induces a global gene expression pattern similar to that induced by red light treatment of seedlings expressing PHYB under the control of its own endogenous promoter. Our results imply that epidermal phyB generates an unidentified mobile signal that travels to the endodermis where it promotes PIF degradation and inhibits hypocotyl negative gravitropism. PMID:27758895

Electronic Two-Transition-Induced Enhancement of Emission Efficiency in Polymer Light-Emitting Diodes

PubMed Central

Chen, Ren-Ai; Wang, Cong; Li, Sheng; George, Thomas F.

2013-01-01

With the development of experimental techniques, effective injection and transportation of electrons is proven as a way to obtain polymer light-emitting diodes (PLEDs) with high quantum efficiency. This paper reveals a valid mechanism for the enhancement of quantum efficiency in PLEDs. When an external electric field is applied, the interaction between a negative polaron and triplet exciton leads to an electronic two-transition process, which induces the exciton to emit light and thus improve the emission efficiency of PLEDs. PMID:28809346

Negative phototropism is seen in Arabidopsis inflorescences when auxin signaling is reduced to a minimal level by an Aux/IAA dominant mutation, axr2.

PubMed

Sato, Atsuko; Sasaki, Shu; Matsuzaki, Jun; Yamamoto, Kotaro T

2015-01-01

Inflorescences of a dominant mutant of Arabidopsis Aux/IAA7, axr2, showed negative phototropism with a similar fluence response curve to the positive phototropism of wild-type stems. Application of a synthetic auxin, NAA, and an inhibitor of polar auxin transport, NPA, increased and decreased respectively the magnitude of the phototropic response in the wild type, while in axr2 application of NAA reduced the negative phototropic response and NPA had no effect. Decapitation of the apex induced a small negative phototropism in wild-type stems, and had no effect in axr2 plants. Inflorescences of the double mutants of auxin transporters, pgp1 pgp19, showed no phototropic response, while decapitation resulted in a negative phototropic response. These results suggest that negative phototropism can occur when the level of auxin or of auxin signaling is reduced to a minimal level, and that in plant axial organs the default phototropic response to unilateral blue light may be negative. Expression of axr2 protein by an endodermis-specific promoter resulted in agravitropism of inflorescences in a similar way to that of axr2, but phototropism was normal, confirming that the endodermis does not play a critical role in phototropism.

Negative phototropism is seen in Arabidopsis inflorescences when auxin signaling is reduced to a minimal level by an Aux/IAA dominant mutation, axr2

PubMed Central

Sato, Atsuko; Sasaki, Shu; Matsuzaki, Jun; Yamamoto, Kotaro T.

2015-01-01

Inflorescences of a dominant mutant of Arabidopsis Aux/IAA7, axr2, showed negative phototropism with a similar fluence response curve to the positive phototropism of wild-type stems. Application of a synthetic auxin, NAA, and an inhibitor of polar auxin transport, NPA, increased and decreased respectively the magnitude of the phototropic response in the wild type, while in axr2 application of NAA reduced the negative phototropic response and NPA had no effect. Decapitation of the apex induced a small negative phototropism in wild-type stems, and had no effect in axr2 plants. Inflorescences of the double mutants of auxin transporters, pgp1 pgp19, showed no phototropic response, while decapitation resulted in a negative phototropic response. These results suggest that negative phototropism can occur when the level of auxin or of auxin signaling is reduced to a minimal level, and that in plant axial organs the default phototropic response to unilateral blue light may be negative. Expression of axr2 protein by an endodermis-specific promoter resulted in agravitropism of inflorescences in a similar way to that of axr2, but phototropism was normal, confirming that the endodermis does not play a critical role in phototropism. PMID:25738325

Blue-light-induced PIN3 polarization for root negative phototropic response in Arabidopsis.

PubMed

Zhang, Kun-Xiao; Xu, Heng-Hao; Yuan, Ting-Ting; Zhang, Liang; Lu, Ying-Tang

2013-10-01

Root negative phototropism is an important response in plants. Although blue light is known to mediate this response, the cellular and molecular mechanisms underlying root negative phototropism remain unclear. Here, we report that the auxin efflux carrier PIN-FORMED (PIN) 3 is involved in asymmetric auxin distribution and root negative phototropism. Unilateral blue-light illumination polarized PIN3 to the outer lateral membrane of columella cells at the illuminated root side, and increased auxin activity at the illuminated side of roots, where auxin promotes growth and causes roots bending away from the light source. Furthermore, root negative phototropic response and blue-light-induced PIN3 polarization were modulated by a brefeldin A-sensitive, GNOM-dependent, trafficking pathway and by phot1-regulated PINOID (PID)/PROTEIN PHOSPHATASE 2A (PP2A) activity. Our results indicate that blue-light-induced PIN3 polarization is needed for asymmetric auxin distribution during root negative phototropic response. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Glycogen synthase kinase-3 negatively regulates anti-inflammatory interleukin-10 for lipopolysaccharide-induced iNOS/NO biosynthesis and RANTES production in microglial cells

PubMed Central

Huang, Wei-Ching; Lin, Yee-Shin; Wang, Chi-Yun; Tsai, Cheng-Chieh; Tseng, Hsiang-Chi; Chen, Chia-Ling; Lu, Pei-Jung; Chen, Po-See; Qian, Li; Hong, Jau-Shyong; Lin, Chiou-Feng

2009-01-01

The inflammatory effects of glycogen synthase kinase-3 (GSK-3) have been identified; however, the potential mechanism is still controversial. In this study, we investigated the effects of GSK-3-mediated interleukin-10 (IL-10) inhibition on lipopolysaccharide (LPS)-induced inflammation. Treatment with GSK-3 inhibitor significantly blocked LPS-induced nitric oxide (NO) production as well as inducible NO synthase (iNOS) expression in BV2 murine microglial cells and primary rat microglia-enriched cultures. Using an antibody array and enzyme-linked immunosorbent assay, we found that GSK-3-inhibitor treatment blocked LPS-induced upregulation of regulated on activation normal T-cell expressed and secreted (RANTES) and increased IL-10 expression. The time kinetics and dose–response relations were confirmed. Reverse transcription–polymerase chain reaction showed changes on the messenger RNA level as well. Inhibiting GSK-3 using short-interference RNA, and transfecting cells with dominant-negative GSK-3β, blocked LPS-elicited NO and RANTES expression but increased IL-10 expression. In contrast, GSK-3β overexpression upregulated NO and RANTES but downregulated IL-10 in LPS-stimulated cells. Treating cells with anti-IL-10 neutralizing antibodies to prevent GSK-3 from downregulating NO and RANTES showed that the anti-inflammatory effects are, at least in part, IL-10-dependent. The involvement of Akt, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase and nuclear factor-κB that positively regulated IL-10 was demonstrated. Furthermore, inhibiting GSK-3 increased the nuclear translocation of transcription factors, that all important for IL-10 expression, including CCAAT/enhancer-binding protein beat (C/EBPβ), C/EBPδ, cAMP response binding element protein and NF-κB. Taken together, these findings reveal that LPS induces iNOS/NO biosynthesis and RANTES production through a mechanism involving GSK-3-mediated IL-10 downregulation. PMID:19175796

Glycogen synthase kinase-3 negatively regulates anti-inflammatory interleukin-10 for lipopolysaccharide-induced iNOS/NO biosynthesis and RANTES production in microglial cells.

PubMed

Huang, Wei-Ching; Lin, Yee-Shin; Wang, Chi-Yun; Tsai, Cheng-Chieh; Tseng, Hsiang-Chi; Chen, Chia-Ling; Lu, Pei-Jung; Chen, Po-See; Qian, Li; Hong, Jau-Shyong; Lin, Chiou-Feng

2009-09-01

The inflammatory effects of glycogen synthase kinase-3 (GSK-3) have been identified; however, the potential mechanism is still controversial. In this study, we investigated the effects of GSK-3-mediated interleukin-10 (IL-10) inhibition on lipopolysaccharide (LPS)-induced inflammation. Treatment with GSK-3 inhibitor significantly blocked LPS-induced nitric oxide (NO) production as well as inducible NO synthase (iNOS) expression in BV2 murine microglial cells and primary rat microglia-enriched cultures. Using an antibody array and enzyme-linked immunosorbent assay, we found that GSK-3-inhibitor treatment blocked LPS-induced upregulation of regulated on activation normal T-cell expressed and secreted (RANTES) and increased IL-10 expression. The time kinetics and dose-response relations were confirmed. Reverse transcription-polymerase chain reaction showed changes on the messenger RNA level as well. Inhibiting GSK-3 using short-interference RNA, and transfecting cells with dominant-negative GSK-3beta, blocked LPS-elicited NO and RANTES expression but increased IL-10 expression. In contrast, GSK-3beta overexpression upregulated NO and RANTES but downregulated IL-10 in LPS-stimulated cells. Treating cells with anti-IL-10 neutralizing antibodies to prevent GSK-3 from downregulating NO and RANTES showed that the anti-inflammatory effects are, at least in part, IL-10-dependent. The involvement of Akt, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase and nuclear factor-kappaB that positively regulated IL-10 was demonstrated. Furthermore, inhibiting GSK-3 increased the nuclear translocation of transcription factors, that all important for IL-10 expression, including CCAAT/enhancer-binding protein beat (C/EBPbeta), C/EBPdelta, cAMP response binding element protein and NF-kappaB. Taken together, these findings reveal that LPS induces iNOS/NO biosynthesis and RANTES production through a mechanism involving GSK-3-mediated IL-10 downregulation.

Radiation effects in concrete for nuclear power plants, Part II: Perspective from micromechanical modeling

DOE PAGES

Le Pape, Yann; Field, Kevin G.; Remec, Igor

2014-11-15

The need to understand and characterize the effects of neutron irradiation on concrete has become urgent because of the possible extension of service life of many nuclear power generating stations. Current knowledge is primarily based on a collection of data obtained in test reactors. These results are inherently difficult to interpret because materials and testing conditions are inconsistent. A micromechanical approach based on the Hashin composite sphere model is presented to derive a first-order separation of the effects of radiation on cement paste and aggregate, and, also, on their interaction. Although the scarcity of available data limits the validation ofmore » the model, it appears that, without negating a possible gamma-ray induced effect, the neutron-induced damage and swelling of aggregate plays a predominant role on the overall concrete expansion and the damage of the cement paste. Finally, the radiation-induced volumetric expansion (RIVE) effects can also be aided by temperature elevation and shrinkage in the cement paste.« less

Weakening of negative relative to positive associations with cocaine-paired cues contributes to cue-induced responding after drug removal.

PubMed

Su, Zu-In; Kichaev, Gleb; Wenzel, Jennifer; Ben-Shahar, Osnat; Ettenberg, Aaron

2012-01-01

Cocaine has been shown to have initial positive (euphoric) and delayed negative (anxiogenic) effects in both humans and animals. Cocaine-paired cues are consequently imbued with mixed positive and negative associations. The current study examines the relative roles of these dual associations in the enhanced drug-seeking observed upon presentation of cocaine-paired cues. Rats ran a straight alley once/day for a single i.v. injection of cocaine (1.0 mg/kg/inj) in the presence of a distinctive olfactory cue (scented cotton swabs placed under the apparatus). An alternate scent was presented in a separate cage 2-h prior to runway testing. After 15 trials/days, the scents and cocaine reinforcer were removed and a series of extinction trials (lasting for 1 or 3 weeks) was initiated. Immediately following extinction, runway responding was tested during a single trial in the presence of the cocaine-paired or non-paired cue. As previously reported, while subjects initiated responding faster over trials (reduced latencies to leave the start box), they exhibited a progressive increase in approach-avoidance conflict behavior ("retreats") regarding goal-box entry, reflecting cocaine's dual positive+negative effects. Once established, retreat behaviors persisted over the course of 1 or 3 weeks days of extinction. However, both run times and retreats decreased in response to presentation of the cocaine-paired but not the non-paired scent. These data suggest that, after reinforcer removal, cue-induced cocaine-seeking stems in part from a reduction in approach-avoidance conflict; i.e., a greater weakening of the negative relative to the positive associations that animals form with cocaine-paired stimuli. Copyright © 2011 Elsevier Inc. All rights reserved.

Phase time delay and Hartman effect in a one-dimensional photonic crystal with four-level atomic defect layer

NASA Astrophysics Data System (ADS)

Jamil, Rabia; Ali, Abu Bakar; Abbas, Muqaddar; Badshah, Fazal; Qamar, Sajid

2017-08-01

The Hartman effect is revisited using a Gaussian beam incident on a one-dimensional photonic crystal (1DPC) having a defect layer doped with four-level atoms. It is considered that each atom of the defect layer interacts with three driving fields, whereas a Gaussian beam of width w is used as a probe light to study Hartman effect. The atom-field interaction inside the defect layer exhibits electromagnetically induced transparency (EIT). The 1DPC acts as positive index material (PIM) and negative index material (NIM) corresponding to the normal and anomalous dispersion of the defect layer, respectively, via control of the phase associated with the driving fields and probe detuning. The positive and negative Hartman effects are noticed for PIM and NIM, respectively, via control of the relative phase corresponding to the driving fields and probe detuning. The advantage of using four-level EIT system is that a much smaller absorption of the transmitted beam occurs as compared to three-level EIT system corresponding to the anomalous dispersion, leading to negative Hartman effect.

Effects of cariprazine, a novel antipsychotic, on cognitive deficit and negative symptoms in a rodent model of schizophrenia symptomatology.

PubMed

Neill, Jo C; Grayson, Ben; Kiss, Béla; Gyertyán, István; Ferguson, Paul; Adham, Nika

2016-01-01

Negative symptoms and cognitive impairment associated with schizophrenia are strongly associated with poor functional outcome and reduced quality of life and remain an unmet clinical need. Cariprazine is a dopamine D3/D2 receptor partial agonist with preferential binding to D3 receptors, recently approved by the FDA for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder. The aim of this study is to evaluate effects of cariprazine in an animal model of cognitive deficit and negative symptoms of schizophrenia. Following sub-chronic PCP administration (2mg/kg, IP for 7 days followed by 7 days drug-free), female Lister Hooded rats were administered cariprazine (0.05, 0.1, or 0.25mg/kg, PO) or risperidone (0.16 or 0.1mg/kg, IP) before testing in novel object recognition (NOR), reversal learning (RL), and social interaction (SI) paradigms. As we have consistently demonstrated, sub-chronic PCP significantly impaired behavior in these tests. Deficits were significantly improved by cariprazine, in a dose dependent manner in the operant RL test with efficacy at lower doses in the NOR and SI tests. Locomotor activity was reduced at the highest doses of 0.1mg/kg and 0.25mg/kg in NOR and SI. Risperidone also reversed the PCP-induced deficit in all tests. In conclusion, cariprazine was effective to overcome PCP-induced deficits in cognition and social behavior in a thoroughly validated rat model in tests representing specific symptom domains in schizophrenia patients. These findings support very recent results showing efficacy of cariprazine in the treatment of negative symptoms in schizophrenia patients. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Adaptability and specificity of inhibition processes in distractor-induced blindness.

PubMed

Winther, Gesche N; Niedeggen, Michael

2017-12-01

In a rapid serial visual presentation task, inhibition processes cumulatively impair processing of a target possessing distractor properties. This phenomenon-known as distractor-induced blindness-has thus far only been elicited using dynamic visual features, such as motion and orientation changes. In three ERP experiments, we used a visual object feature-color-to test for the adaptability and specificity of the effect. In Experiment I, participants responded to a color change (target) in the periphery whose onset was signaled by a central cue. Presentation of irrelevant color changes prior to the cue (distractors) led to reduced target detection, accompanied by a frontal ERP negativity that increased with increasing number of distractors, similar to the effects previously found for dynamic targets. This suggests that distractor-induced blindness is adaptable to color features. In Experiment II, the target consisted of coherent motion contrasting the color distractors. Correlates of distractor-induced blindness were found neither in the behavioral nor in the ERP data, indicating a feature specificity of the process. Experiment III confirmed the strict distinction between congruent and incongruent distractors: A single color distractor was embedded in a stream of motion distractors with the target consisting of a coherent motion. While behavioral performance was affected by the distractors, the color distractor did not elicit a frontal negativity. The experiments show that distractor-induced blindness is also triggered by visual stimuli predominantly processed in the ventral stream. The strict specificity of the central inhibition process also applies to these stimulus features. © 2017 Society for Psychophysiological Research.

Improved pertussis vaccines based on adjuvants that induce cell-mediated immunity.

PubMed

Allen, Aideen C; Mills, Kingston H G

2014-10-01

Bordetella pertussis is a Gram-negative bacterium that causes the severe and sometimes lethal respiratory disease whooping cough in infants and children. There has been a recent resurgence in the number of cases of pertussis in several countries with high vaccine coverage. This has been linked with waning or ineffective immunity induced by current acellular pertussis vaccines. These acellular pertussis vaccines are formulated with alum as the adjuvant, which promotes strong antibody responses but is less effective at inducing Th1-type responses crucial for effective bacterial clearance. Studies in animal models have demonstrated that replacing alum with alternative adjuvants, such as toll-like receptor agonists, can promote more robust cell-mediated immunity and confer a high level of protection against infection following respiratory challenge.

Misfortune may be a blessing in disguise: Fairness perception and emotion modulate decision making.

PubMed

Liu, Hong-Hsiang; Hwang, Yin-Dir; Hsieh, Ming H; Hsu, Yung-Fong; Lai, Wen-Sung

2017-08-01

Fairness perception and equality during social interactions frequently elicit affective arousal and affect decision making. By integrating the dictator game and a probabilistic gambling task, this study aimed to investigate the effects of a negative experience induced by perceived unfairness on decision making using behavioral, model fitting, and electrophysiological approaches. Participants were randomly assigned to the neutral, harsh, or kind groups, which consisted of various asset allocation scenarios to induce different levels of perceived unfairness. The monetary gain was subsequently considered the initial asset in a negatively rewarded, probabilistic gambling task in which the participants were instructed to maintain as much asset as possible. Our behavioral results indicated that the participants in the harsh group exhibited increased levels of negative emotions but retained greater total game scores than the participants in the other two groups. Parameter estimation of a reinforcement learning model using a Bayesian approach indicated that these participants were more loss aversive and consistent in decision making. Data from simultaneous ERP recordings further demonstrated that these participants exhibited larger feedback-related negativity to unexpected outcomes in the gambling task, which suggests enhanced reward sensitivity and signaling of reward prediction error. Collectively, our study suggests that a negative experience may be an advantage in the modulation of reward-based decision making. © 2017 Society for Psychophysiological Research.

Conceptualizing withdrawal-induced escalation of alcohol self-administration as a learned, plasticity-dependent process

PubMed Central

Walker, Brendan M.

2013-01-01

This article represents one of five contributions focusing on the topic “Plasticity and neuroadaptive responses within the extended amygdala in response to chronic or excessive alcohol exposure” that were developed by awardees participating in the Young Investigator Award Symposium at the “Alcoholism and Stress: A Framework for Future Treatment Strategies” conference in Volterra, Italy on May 3–6, 2011 that was organized/chaired by Drs. Antonio Noronha and Fulton Crews and sponsored by the National Institute on Alcohol Abuse and Alcoholism. This review discusses the dependence-induced neuroadaptations in affective systems that provide a basis for negative reinforcement learning and presents evidence demonstrating that escalated alcohol consumption during withdrawal is a learned, plasticity-dependent process. The review concludes by identifying changes within extended amygdala dynorphin/kappa-opioid receptor systems that could serve as the foundation for the occurrence of negative reinforcement processes. While some evidence contained herein may be specific to alcohol dependence-related learning and plasticity, much of the information will be of relevance to any addictive disorder involving negative reinforcement mechanisms. Collectively, the information presented within this review provides a framework to assess the negative reinforcing effects of alcohol in a manner that distinguishes neuroadaptations produced by chronic alcohol exposure from the actual plasticity that is associated with negative reinforcement learning in dependent organisms. PMID:22459874

[Secondary osteoporosis induced by anticoagulants?].

PubMed

Riess, H; Loew, A; Himmelreich, G

2001-07-01

Generalized osteoporosis is a result of different causes and pathogenic mechanisms, which often combine forces to become clinically relevant. Among the different exogenic factors, drugs play an important role, frequently in connection with other factors such as immobilization or pregnancy. It has been suggested that anticoagulation therapy with heparins or coumarins may induce osteoporotic changes or enhance the development of osteoporosis for other reasons. According to in vitro experiments, preclinical trials, and clinical investigations, it seems reasonable to assume that heparins induce increased bone loss in a time- and dose-related manner. Low-molecular-weight heparins most likely have less effect on bone turnover when compared to unfractionated heparin. Oral anticoagulation therapy with vitamin K-antagonists is believed to have a weak effect on induction of osteoporosis, but clinical studies are contradictory. In spite of the fact that a relevant effect of these drugs on the induction of osteoporosis is questionable, it must be taken into consideration that anticoagulant drugs may enhance the negative effects on bone density of other risk factors capable of inducing osteoporosis such as immobilization, pregnancy, or endocrinological disorders.

Effect of Mood on Children's Giving.

ERIC Educational Resources Information Center

Underwood, Bill; And Others

1972-01-01

An experiment was conducted to clarify the relations between affect and altruism by inducing affect directly. It was hypothesized that children who experienced positive affect would share more than controls, while those experiencing negative affect would share significantly less than controls. Ss were 25 girls and 18 boys from the second and third…

Information and Attitudes toward Disability.

ERIC Educational Resources Information Center

Hafer, Marilyn; Narcus, Margery

1979-01-01

Examined effects of two movies, Like Other People and The Music Box, on attitudes as measured by the Attitudes toward Disabled Persons scale. Results indicated more negative attitudes were induced in pretested participants by Like Other People at initial post-test; however, more favorable attitudes were exhibited by participants six weeks later.…

The effect of nutrient media water purity on LIBS based identification of bacteria

USDA-ARS?s Scientific Manuscript database

Single pulse laser induced breakdown spectroscopy (LIBS) is used as the basis for discrimination between 3 genera of Gram-negative bacteria and 2 genera of gram-positive bacteria representing pathogenic threats commonly found in poultry processing rinse waters. Because LIBS-based discrimination reli...

Effects of delay and noise in a negative feedback regulatory motif

NASA Astrophysics Data System (ADS)

Palassini, Matteo; Dies, Marta

2009-03-01

The small copy number of the molecules involved in gene regulation can induce nontrivial stochastic phenomena such as noise-induced oscillations. An often neglected aspect of regulation dynamics are the delays involved in transcription and translation. Delays introduce analytical and computational complications because the dynamics is non-Markovian. We study the interplay of noise and delays in a negative feedback model of the p53 core regulatory network. Recent experiments have found pronounced oscillations in the concentrations of proteins p53 and Mdm2 in individual cells subjected to DNA damage. Similar oscillations occur in the Hes-1 and NK-kB systems, and in circadian rhythms. Several mechanisms have been proposed to explain this oscillatory behaviour, such as deterministic limit cycles, with and without delay, or noise-induced excursions in excitable models. We consider a generic delayed Master Equation incorporating the activation of Mdm2 by p53 and the Mdm2-promoted degradation of p53. In the deterministic limit and for large delays, the model shows a Hopf bifurcation. Via exact stochastic simulations, we find strong noise-induced oscillations well outside the limit-cycle region. We propose that this may be a generic mechanism for oscillations in gene regulatory systems.

Sensing and Responding to UV-A in Cyanobacteria

PubMed Central

Moon, Yoon-Jung; Kim, Seung Il; Chung, Young-Ho

2012-01-01

Ultraviolet (UV) radiation can cause stresses or act as a photoregulatory signal depending on its wavelengths and fluence rates. Although the most harmful effects of UV on living cells are generally attributed to UV-B radiation, UV-A radiation can also affect many aspects of cellular processes. In cyanobacteria, most studies have concentrated on the damaging effect of UV and defense mechanisms to withstand UV stress. However, little is known about the activation mechanism of signaling components or their pathways which are implicated in the process following UV irradiation. Motile cyanobacteria use a very precise negative phototaxis signaling system to move away from high levels of solar radiation, which is an effective escape mechanism to avoid the detrimental effects of UV radiation. Recently, two different UV-A-induced signaling systems for regulating cyanobacterial phototaxis were characterized at the photophysiological and molecular levels. Here, we review the current understanding of the UV-A mediated signaling pathways in the context of the UV-A perception mechanism, early signaling components, and negative phototactic responses. In addition, increasing evidences supporting a role of pterins in response to UV radiation are discussed. We outline the effect of UV-induced cell damage, associated signaling molecules, and programmed cell death under UV-mediated oxidative stress. PMID:23208372

Framing effects: the influence of handedness and access to right hemisphere processing.

PubMed

Stein, Jeannette M

2012-01-01

Changing how information is framed, such that the same critical information is cast in a positive or negative light, has a powerful impact on judgements and decision making. Research indicates that the influence of frames may be driven by participants' initial affective response and that the right hemisphere is sensitive to the emotional connotation of stimuli. While previous research tested the effects of hemispheric differences on framing effects by inducing asymmetrical activation, the current study explored how stable brain differences may account for differences in susceptibility to framing effects. Because mixed degree of handedness is associated with increased access to right hemisphere processes, mixed-handed participants were expected to be more susceptible to the effects of framing than strong-handed participants. Participants responded to the Asian disease problem and completed as assessment of handedness. Although mixed- and strong-handed participants were affected differently, the results were not consistent with the hypothesis. Mixed-handed participants conformed to risky choice framing effects when options were framed negatively and showed no effect of the positive frame. Strong-handed participants conformed to positively framed options and showed no effect of the negative frame. Possible explanations are discussed.

SPATHOLOBUS SUBERECTUS STEM EXTRACT IMPROVES THE PROTECTIVE EFFECT OF HEPARIN ON CERULEIN-INDUCED PANCREATITIS.

PubMed

Shao, Zhengyi

2017-01-01

The present study evaluates the effect of Spatholobus suberectus stem extract (SS) in the management of pancreatitis alone and in combination with heparin. Pancreatitis was induced pancreatitis by cerulean (50μg/kg, i.p.) five times at an interval of 1 h without any pretreatment of drug. Rats were treated with SS (100 and 200 mg/kg, p. o.) and heparin (150 U/kg, i.p.) alone and in combination for the duration of a week. Later pancreatic weight and blood flow was estimated and different biochemical parameters like concentration of D-dimer and Interleukin 1β (IL-Ιβ) and activity of amylase and lipase were determined in blood of pancreatitis rats. Moreover effect of drug treatment on DNA synthesis and histopathology was also estimated on cerulean induced pancreatitis rats. Results of this study suggest that treatment with SS alone and in combination with heparin significantly increase in prothrombin time and pancreatic blood flow than negative control group. There was significant decrease in concentration of IL-Ιβ and D-dimer and activity of amylase and lipase in SS and heparin treated group than negative control group. Pancreatic DNA synthesis was also found to be reduced in SS and heparin alone and in combination treated group. Histopathology study also reveals that treatment with SS and heparin alone and in combination reduces edema, hemorrhages, leukocyte infiltration in the TS of pancreatic tissues. Present study concludes that treatment with SS alone effectively manages the pancreatitis by ceasing the inflammatory pathway and potentiates the effect of heparin in the management of pancreatitis.

Niclosamide inhibits leaf blight caused by Xanthomonas oryzae in rice

PubMed Central

Kim, Sung-Il; Song, Jong Tae; Jeong, Jin-Yong; Seo, Hak Soo

2016-01-01

Rice leaf blight, which is caused by the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo), results in huge losses in grain yield. Here, we show that Xoo-induced rice leaf blight is effectively controlled by niclosamide, an oral antihelminthic drug and molluscicide, which also functions as an anti-tumor agent. Niclosamide directly inhibited the growth of the three Xoo strains PXO99, 10208 and K3a. Niclosamide moved long distances from the site of local application to distant rice tissues. Niclosamide also increased the levels of salicylate and induced the expression of defense-related genes such as OsPR1 and OsWRKY45, which suppressed Xoo-induced leaf wilting. Niclosamide had no detrimental effects on vegetative/reproductive growth and yield. These combined results indicate that niclosamide can be used to block bacterial leaf blight in rice with no negative side effects. PMID:26879887

BISPHENOL A INTERFERES WITH SYNAPTIC REMODELING

PubMed Central

Hajszan, Tibor; Leranth, Csaba

2010-01-01

The potential adverse effects of Bisphenol A (BPA), a synthetic xenoestrogen, have long been debated. Although standard toxicology tests have revealed no harmful effects, recent research highlighted what was missed so far: BPA-induced alterations in the nervous system. Since 2004, our laboratory has been investigating one of the central effects of BPA, which is interference with gonadal steroid-induced synaptogenesis and the resulting loss of spine synapses. We have shown in both rats and nonhuman primates that BPA completely negates the ~70–100% increase in the number of hippocampal and prefrontal spine synapses induced by both estrogens and androgens. Synaptic loss of this magnitude may have significant consequences, potentially causing cognitive decline, depression, and schizophrenia, to mention those that our laboratory has shown to be associated with synaptic loss. Finally, we discuss why children may particularly be vulnerable to BPA, which represents future direction of research in our laboratory. PMID:20609373

Ice nucleation triggered by negative pressure.

PubMed

Marcolli, Claudia

2017-11-30

Homogeneous ice nucleation needs supercooling of more than 35 K to become effective. When pressure is applied to water, the melting and the freezing points both decrease. Conversely, melting and freezing temperatures increase under negative pressure, i.e. when water is stretched. This study presents an extrapolation of homogeneous ice nucleation temperatures from positive to negative pressures as a basis for further exploration of ice nucleation under negative pressure. It predicts that increasing negative pressure at temperatures below about 262 K eventually results in homogeneous ice nucleation while at warmer temperature homogeneous cavitation, i. e. bubble nucleation, dominates. Negative pressure occurs locally and briefly when water is stretched due to mechanical shock, sonic waves, or fragmentation. The occurrence of such transient negative pressure should suffice to trigger homogeneous ice nucleation at large supercooling in the absence of ice-nucleating surfaces. In addition, negative pressure can act together with ice-inducing surfaces to enhance their intrinsic ice nucleation efficiency. Dynamic ice nucleation can be used to improve properties and uniformity of frozen products by applying ultrasonic fields and might also be relevant for the freezing of large drops in rainclouds.

Negative emotion boosts quality of visual working memory representation.

PubMed

Xie, Weizhen; Zhang, Weiwei

2016-08-01

Negative emotion impacts a variety of cognitive processes, including working memory (WM). The present study investigated whether negative emotion modulated WM capacity (quantity) or resolution (quality), 2 independent limits on WM storage. In Experiment 1, observers tried to remember several colors over 1-s delay and then recalled the color of a randomly picked memory item by clicking a best-matching color on a continuous color wheel. On each trial, before the visual WM task, 1 of 3 emotion conditions (negative, neutral, or positive) was induced by having observers to rate the valence of an International Affective Picture System image. Visual WM under negative emotion showed enhanced resolution compared with neutral and positive conditions, whereas the number of retained representations was comparable across the 3 emotion conditions. These effects were generalized to closed-contour shapes in Experiment 2. To isolate the locus of these effects, Experiment 3 adopted an iconic memory version of the color recall task by eliminating the 1-s retention interval. No significant change in the quantity or quality of iconic memory was observed, suggesting that the resolution effects in the first 2 experiments were critically dependent on the need to retain memory representations over a short period of time. Taken together, these results suggest that negative emotion selectively boosts visual WM quality, supporting the dissociable nature quantitative and qualitative aspects of visual WM representation. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Ground-Based High-Power Microwave Decoy Discrimination System.

DTIC Science & Technology

1987-12-23

understanding of plasma instabilities, self-induced magnetic effects , space - charge considerations, production of ion currents, etc. 3.3.4 Cross-Field...breakdown, due to small potential differences. Interaction volumes can therefore be large, avoiding breakdown and space - charge effects (at the price...the interference of the incident and reflected wave, and by the electrostatic forces of the surface (positive) and space charge (negative) trapped in

Interferon-gamma exerts its negative regulatory effect primarily on the earliest stages of murine erythroid progenitor cell development.

PubMed

Wang, C Q; Udupa, K B; Lipschitz, D A

1995-01-01

Interferon-gamma (INF-gamma) has been shown to suppress erythropoiesis and perhaps to contribute to the anemia of chronic disease. In this study we demonstrated that the concentration of INF gamma required to suppress murine burst forming unit-erythroid (BFU-E) growth was significantly less than that required to suppress colony forming unit-erythroid (CFU-E) growth. INF gamma acted at the most primitive step in erythroid progenitor cell differentiation and proliferation, as inhibition was maximal when added at the time of BFU-E culture initiation. Inhibition was progressively less if INF gamma addition was delayed after culture initiation. The effects of INF gamma on BFU-E did not require the presence of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF alpha), or granulocyte macrophage colony stimulating factor (GM-CSF), as its effects were not neutralized by monoclonal antibodies against IL-1 alpha, TNF alpha, or GM-CSF. This applied whether INF gamma was added to culture with individual antibodies or with a combination of all three antibodies. INF gamma was not required for IL-1 alpha- or TNF alpha-induced suppression of BFU-E, as their effects were not neutralized by a monoclonal anti-INF gamma antibody. In contrast, GM-CSF-induced suppression of BFU-E was negated by the simultaneous addition of anti-INF gamma. We have previously shown that the addition of TNF alpha does not suppress BFU-E growth in cultures from marrow depleted of macrophages. Suppression did occur, however, if a small concentration of INF gamma that does not inhibit and increasing concentration of TNF alpha were added to culture, suggesting a synergistic effect between INF-gamma and TNF alpha. These observations suggest that INF gamma is a potent direct inhibitor of erythroid colony growth in vitro. It exerts its negative regulatory effect primarily on the earliest stages of erythroid progenitor cell differentiation and proliferation, as much higher doses are required to suppress late erythroid cell development. INF gamma is also involved in GM-CSF-induced inhibition of BFU-E colony growth.

Entanglement between two Rydberg atoms induced by a thermal field

NASA Astrophysics Data System (ADS)

Mastyugina, T. S.; Bashkirov, E. K.

2017-11-01

We investigated two Rydberg atoms successively passing a vacuum or a thermal cavity taking into account the detuning. The atoms was assumed to be initially prepared in the Bell types entangled atomic states. Calculating the negativity we investigated the dynamics of atom-atom entanglement both for the vacuum and the thermal field. The special features of negativity behavior have been studied comprehensively foe small and large values of detunings. For thermal field and small detunings we established the effect of sudden death and birth of entanglement.

Total Ionizing Dose Effects on Ge Channel $p$FETs with Raised $${\\rm Si}_{0.55}{\\rm Ge}_{0.45}$$ Source/Drain

DOE PAGES

Wang, Liang; Zhang, En Xia; Schrimpf, Ronald D.; ...

2015-12-17

Here, the total ionizing dose response of Ge channel pFETs with raised Si 0.55Ge 0.45 source/drain is investigated under different radiation bias conditions. Threshold-voltage shifts and transconductance degradation are noticeable only for negative-bias (on state) irradiation, and are mainly due to negative bias-temperature instability (NBTI). Nonmonotonic leakage changes during irradiation are observed, which are attributed to the competition of radiation-induced field transistor leakage and S/D junction leakage.

Electrical control of optical orientation of neutral and negatively charged excitons in an n -type semiconductor quantum well

NASA Astrophysics Data System (ADS)

Dzhioev, R. I.; Korenev, V. L.; Lazarev, M. V.; Sapega, V. F.; Gammon, D.; Bracker, A. S.

2007-01-01

We report electric field induced increase of spin orientation of negatively charged excitons (trions) localized in n -type GaAs/AlGaAs quantum well. Under resonant excitation of free neutral heavy-hole excitons, the polarization of trions increases dramatically with electrical injection of electrons. The polarization enhancement correlates strongly with trion/exciton luminescence intensity ratio. This effect results from a very efficient trapping of free neutral excitons by the quantum well interfacial fluctuations (“natural” quantum dots) containing resident electrons.

Homemade-device-induced negative pressure promotes wound healing more efficiently than VSD-induced positive pressure by regulating inflammation, proliferation and remodeling.

PubMed

Liu, Jinyan; Hu, Feng; Tang, Jintian; Tang, Shijie; Xia, Kun; Wu, Song; Yin, Chaoqi; Wang, Shaohua; He, Quanyong; Xie, Huiqing; Zhou, Jianda

2017-04-01

Vacuum sealing drainage (VSD) is an effective technique used to promote wound healing. However, recent studies have shown that it exerts positive pressure (PP) rather than negative pressure (NP) on skin. In this study, we created a homemade device that could maintain NP on the wound, and compared the therapeutic effects of VSD-induced PP to those of our homemade device which induced NP on wound healing. The NP induced by our device required less time for wound healing and decreased the wound area more efficiently than the PP induced by VSD. NP and PP both promoted the inflammatory response by upregulating neutrophil infiltration and interleukin (IL)‑1β expression, and downregulating IL‑10 expression. Higher levels of epidermal growth factor (EGF), transforming growth factor (TGF)‑β and platelet-derived growth factor (PDGF), and lower levels of basic fibroblast growth factor (bFGF) were observed in the wound tissue treated with NP compared to the wound tissue exposed to PP. Proliferation in the wound tissue exposed to NP on day 10 was significantly higher than that in wound tissue exposed to PP. NP generated more fibroblasts, keratinized stratified epithelium, and less epithelia with stemness than PP. The levels of ccollagen Ⅰ and Ⅲ were both decreased in both the NP and PP groups. NP induced a statistically significant increase in the expression of fibronectin (FN) on days 3 and 10 compared to PP. Furthermore, the level of matrix metalloproteinase (MMP)‑13 increased in the NP group, but decreased in the PP group on day 3. NP also induced a decrease in the levels of tissue inhibitor of metalloproteinase (TIMP)‑1 and TIMP‑2 during the early stages of wound healing, which was significantly different from the increasing effect of PP on TIMP‑1 and TIMP‑2 levels at the corresponding time points. On the whole, our data indicate that our homemade device which induced NP, was more efficient than VSD‑induced PP on wound healing by regulating inflammation, secretion, proliferation and the distribution of different cells in wound tissue.

Doxycycline inhibits proliferation and induces apoptosis of both human papillomavirus positive and negative cervical cancer cell lines.

PubMed

Zhao, Yan; Wang, Xinyu; Li, Lei; Li, Changzhong

2016-05-01

The clinical management of cervical cancer remains a challenge and the development of new treatment strategies merits attention. However, the discovery and development of novel compounds can be a long and labourious process. Drug repositioning may circumvent this process and facilitate the rapid translation of hypothesis-driven science into the clinics. In this work, we show that a FDA-approved antibiotic, doxycycline, effectively targets human papillomavirus (HPV) positive and negative cervical cancer cells in vitro and in vivo. Doxycycline significantly inhibits proliferation of a panel of cervical cancer cell lines. It also induces apoptosis of cervical cancer cells in a time- and dose-dependent manner. In addition, the apoptosis induced by doxycycline is through caspase-dependent pathway. Mechanism studies demonstrate that doxycycline affects oxygen consumption rate, glycolysis, and reduces ATP levels in cervical cancer cells. In HeLa xenograft mouse model, doxycycline significantly inhibits growth of tumour. Our in vitro and in vivo data clearly demonstrate the inhibitory effects of doxycycline on the growth and survival of cervical cancer cells. Our work provides the evidence that doxycycline can be repurposed for the treatment of cervical cancer and targeting energy metabolism may represent a potential therapeutic strategy for cervical cancer.

Gender, Ethnicity, and their Intersectionality in the Prediction of Smoking Outcome Expectancies in Regular Cigarette Smokers

PubMed Central

Aguirre, Claudia G.; Bello, Mariel S.; Pang, Raina D.; Andrabi, Nafeesa; Hendricks, Peter S.; Bluthenthal, Ricky N.; Leventhal, Adam M.

2016-01-01

The current study utilized the intersectionality framework to explore whether smoking outcome expectancies (i.e., cognitions about the anticipated effects of smoking) were predicted by gender and ethnicity, and the gender-by-ethnicity interaction. In a cross-sectional design, daily smokers from the general community [32.2% women; Non-Hispanic African American (N=175), Non-Hispanic White (N=109), or Hispanic (N=26)] completed self-report measures on smoking expectancies and other co-factors. Results showed that women reported greater negative reinforcement (i.e., anticipated smoking-induced negative affect reduction) and weight control (i.e., anticipated smoking-induced appetite/weight suppression) expectancies than men. Hispanic (vs. African American or White) smokers endorsed greater negative reinforcement expectancies. A gender by ethnicity interaction was found for weight control expectancies, such that White women reported greater weight control expectancies than White men, but no gender differences among African American and Hispanic smokers were found. Ethnicity, gender, and their intersectionality should be considered in smoking cessation programs to target smoking-related cognitions. PMID:26438665

Gender, Ethnicity, and Their Intersectionality in the Prediction of Smoking Outcome Expectancies in Regular Cigarette Smokers.

PubMed

Aguirre, Claudia G; Bello, Mariel S; Andrabi, Nafeesa; Pang, Raina D; Hendricks, Peter S; Bluthenthal, Ricky N; Leventhal, Adam M

2016-01-01

The current study utilized the intersectionality framework to explore whether smoking outcome expectancies (i.e., cognitions about the anticipated effects of smoking) were predicted by gender and ethnicity, and the gender-by-ethnicity interaction. In a cross-sectional design, daily smokers from the general community (32.2% women; non-Hispanic African American [n = 175], non-Hispanic White [n = 109], or Hispanic [n = 26]) completed self-report measures on smoking expectancies and other co-factors. Results showed that women reported greater negative reinforcement (i.e., anticipated smoking-induced negative affect reduction) and weight control (i.e., anticipated smoking-induced appetite/weight suppression) expectancies than men. Hispanic (vs. African American or White) smokers endorsed greater negative reinforcement expectancies. A gender-by-ethnicity interaction was found for weight control expectancies, such that White women reported greater weight control expectancies than White men, but no gender differences among African American and Hispanic smokers were found. These findings suggest that gender, ethnicity, and their intersectionality should be considered in research on cognitive mechanisms that may contribute to tobacco-related health disparities. © The Author(s) 2015.

Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator.

PubMed

Font, Joan; López-Cano, Marc; Notartomaso, Serena; Scarselli, Pamela; Di Pietro, Paola; Bresolí-Obach, Roger; Battaglia, Giuseppe; Malhaire, Fanny; Rovira, Xavier; Catena, Juanlo; Giraldo, Jesús; Pin, Jean-Philippe; Fernández-Dueñas, Víctor; Goudet, Cyril; Nonell, Santi; Nicoletti, Ferdinando; Llebaria, Amadeu; Ciruela, Francisco

2017-04-11

Light-operated drugs constitute a major target in drug discovery, since they may provide spatiotemporal resolution for the treatment of complex diseases (i.e. chronic pain). JF-NP-26 is an inactive photocaged derivative of the metabotropic glutamate type 5 (mGlu 5 ) receptor negative allosteric modulator raseglurant. Violet light illumination of JF-NP-26 induces a photochemical reaction prompting the active-drug's release, which effectively controls mGlu 5 receptor activity both in ectopic expressing systems and in striatal primary neurons. Systemic administration in mice followed by local light-emitting diode (LED)-based illumination, either of the thalamus or the peripheral tissues, induced JF-NP-26-mediated light-dependent analgesia both in neuropathic and in acute/tonic inflammatory pain models. These data offer the first example of optical control of analgesia in vivo using a photocaged mGlu 5 receptor negative allosteric modulator. This approach shows potential for precisely targeting, in time and space, endogenous receptors, which may allow a better management of difficult-to-treat disorders.

Precursor of superfluidity in a strongly interacting Fermi gas with negative effective range

NASA Astrophysics Data System (ADS)

Tajima, Hiroyuki

2018-04-01

We investigate theoretically the effects of pairing fluctuations in an ultracold Fermi gas near a Feshbach resonance with a negative effective range. By employing a many-body T -matrix theory with a coupled fermion-boson model, we show that the single-particle density of states exhibits the so-called pseudogap phenomenon, which is a precursor of superfluidity induced by strong pairing fluctuations. We clarify the region where strong pairing fluctuations play a crucial role in single-particle properties, from the broad-resonance region to the narrow-resonance limit at the divergent two-body scattering length. We also extrapolate the effects of pairing fluctuations to the positive-effective-range region from our results near the narrow Feshbach resonance. Results shown in this paper are relevant to the connection between ultracold Fermi gases and low-density neutron matter from the viewpoint of finite-effective-range corrections.

N-terminal tyrosine phosphorylation of caveolin-2 negates anti-proliferative effect of transforming growth factor beta in endothelial cells

PubMed Central

Abel, Britain; Willoughby, Cara; Jang, Sungchan; Cooper, Laura; Xie, Leike; Vo-Ransdell, Chi; Sowa, Grzegorz

2012-01-01

Here we show that tyrosine phosphorylation of caveolin-2 (Cav-2) negatively regulates the anti-proliferative function of transforming growth factor beta (TGF-beta) in endothelial cells. In contrast to wild-type-Cav-2, retroviral re-expression of Y19/27F-Cav-2 in Cav-2 knockout endothelial cells did not affect anti-proliferative effect of TGF-beta compared to empty vector. Conversely, although less effective than wild-type, re-expression of S23/36A-Cav-2 reduced the effect of TGF-beta compared to empty vector. This differential effect of tyrosine and serine phosphorylation mutants of Cav-2 correlated with TGF-beta-induced Smad3 phosphorylation and transcriptional activation of plasminogen activator inhibitor-1. Thus tyrosine-phosphorylated Cav-2 counteracts anti-proliferative effect of TGF-beta in endothelial cells. PMID:22819829

The Quantity-Quality Trade-Off of Children in a Developing Country: Identification Using Chinese Twins

PubMed Central

LI, HONGBIN; ZHANG, JUNSEN; ZHU, YI

2008-01-01

Testing the trade-off between child quantity and quality within a family is complicated by the endogeneity of family size. Using data from the Chinese Population Census, we examine the effect of family size on child educational attainment in China. We find a negative correlation between family size and child outcome, even after we control for the birth order effect. We then instrument family size by the exogenous variation that is induced by a twin birth and find a negative effect of family size on children’s education. We also find that the effect of family size is more evident in rural China, where the public education system is poor. Given that our estimates of the effect of having twins on nontwins at least provide the lower bound of the true effect of family size, these findings suggest a quantity-quality trade-off for children in developing countries. PMID:18390301

The quantity-quality trade-off of children in a developing country: identification using Chinese twins.

PubMed

Li, Hongbin; Zhang, Junsen; Zhu, Yi

2008-02-01

Testing the trade-off between child quantity and quality within a family is complicated by the endogeneity of family size. Using data from the Chinese Population Census, we examine the effect of family size on child educational attainment in China. We find a negative correlation between family size and child outcome, even after we control for the birth order effect. We then instrument family size by the exogenous variation that is induced by a twin birth and find a negative effect offamily size on children's education. We also find that the effect of family size is more evident in rural China, where the public education system is poor. Given that our estimates of the effect of having twins on nontwins at least provide the lower bound of the true effect of family size, these findings suggest a quantity-quality trade-off for children in developing countries.

Gunn-Hilsum Effect in Mechanically Strained Silicon Nanowires: Tunable Negative Differential Resistance.

PubMed

Shiri, Daryoush; Verma, Amit; Nekovei, Reza; Isacsson, Andreas; Selvakumar, C R; Anantram, M P

2018-04-19

Gunn (or Gunn-Hilsum) Effect and its associated negative differential resistivity (NDR) emanates from transfer of electrons between two different energy subbands. This effect was observed in semiconductors like GaAs which has a direct bandgap of very low effective mass and an indirect subband of high effective mass which lies ~300 meV above the former. In contrast to GaAs, bulk silicon has a very high energy spacing (~1 eV) which renders the initiation of transfer-induced NDR unobservable. Using Density Functional Theory (DFT), semi-empirical 10 orbital (sp 3 d 5 s * ) Tight Binding and Ensemble Monte Carlo (EMC) methods we show for the first time that (a) Gunn Effect can be induced in silicon nanowires (SiNW) with diameters of 3.1 nm under +3% strain and an electric field of 5000 V/cm, (b) the onset of NDR in the I-V characteristics is reversibly adjustable by strain and (c) strain modulates the resistivity by a factor 2.3 for SiNWs of normal I-V characteristics i.e. those without NDR. These observations are promising for applications of SiNWs in electromechanical sensors and adjustable microwave oscillators. It is noteworthy that the observed NDC is different in principle from Esaki-Diode and Resonant Tunneling Diodes (RTD) in which NDR originates from tunneling effect.

Hole-exciton interaction induced high field decay of magneto-electroluminescence in Alq3-based organic light-emitting diodes at room temperature

NASA Astrophysics Data System (ADS)

Zhang, Tingting; Holford, D. F.; Gu, Hang; Kreouzis, T.; Zhang, Sijie; Gillin, W. P.

2016-01-01

The magnetic field effects on the electroluminescence of aluminium tris-(8-hydroxyqinoline) (Alq3) based organic light emitting diodes have been investigated by varying the electron/hole ratio in the emissive layer. Experimental results reveal that a negative high field effect in the magneto-electroluminescence (MEL) can be found in devices with very low triplet exciton concentration at room temperature. This suggests triplet-triplet annihilation cannot be used to explain the negative high field MEL in the Alq3 system. Our results suggest that hole-exciton interaction may be the origin of the negative high field MEL and also, in parallel with this interaction, there is also the more common positive high field process occurring which has been tentatively attributed to electron-exciton interactions. The competition between these different processes decides the final shape of the MEL at high fields.

Triptolide inhibits TGF-β1-induced cell proliferation in rat airway smooth muscle cells by suppressing Smad signaling

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

Chen, Ming; Lv, Zhiqiang; Huang, Linjie

Background: We have reported that triptolide can inhibit airway remodeling in a murine model of asthma via TGF-β1/Smad signaling. In the present study, we aimed to investigate the effect of triptolide on airway smooth muscle cells (ASMCs) proliferation and the possible mechanism. Methods: Rat airway smooth muscle cells were cultured and made synchronized, then pretreated with different concentration of triptolide before stimulated by TGF-β1. Cell proliferation was evaluated by MTT assay. Flow cytometry was used to study the influence of triptolide on cell cycle and apoptosis. Signal proteins (Smad2, Smad3 and Smad7) were detected by western blotting analysis. Results: Triptolidemore » significantly inhibited TGF-β1-induced ASMC proliferation (P<0.05). The cell cycle was blocked at G1/S-interphase by triptolide dose dependently. No pro-apoptotic effects were detected under the concentration of triptolide we used. Western blotting analysis showed TGF-β1 induced Smad2 and Smad3 phosphorylation was inhibited by triptolide pretreatment, and the level of Smad7 was increased by triptolide pretreatment. Conclusions: Triptolide may function as an inhibitor of asthma airway remodeling by suppressing ASMCs proliferation via negative regulation of Smad signaling pathway. - Highlights: • In this study, rat airway smooth muscle cells were cultured and made synchronized. • Triptolide inhibited TGF-β1-induced airway smooth muscle cells proliferation. • Triptolide inhibited ASMCs proliferation via negative regulation of Smad signaling pathway.« less

Solidification structures grown under induced flow and continuous casting of steel

NASA Technical Reports Server (NTRS)

Tsavaras, A. A.

1984-01-01

The use of induced flow as a means to control solidification structures in strand cast steel is investigated. The quality problems in strand cast steel stemming from columnar growth can be partially controlled, by Electro Magnetic Stirring (EMS). Induced flow changes the normal morphology of dendrites. Solids grown under intense stirring conditions show both negative and positive segregation which is considered unacceptable by some steel producers. The inclusion size and population is strongly affected by induced flow (EMS). Laboratory and industrial data show substantial reduction in inclusion size and content, but the overall effect of flow on inclusions is affected by the particular type of flow patterns utilized in each case. Productivity and quality are raised substantially in steel strand casting by utilizing EMS.

A Synthetic Triterpenoid CDDO-Im Inhibits Tumorsphere Formation by Regulating Stem Cell Signaling Pathways in Triple-Negative Breast Cancer

PubMed Central

Wahler, Joseph; Liby, Karen T.; Sporn, Michael B.; Suh, Nanjoo

2014-01-01

Triple-negative breast cancer is associated with poor prognosis because of a high rate of tumor recurrence and metastasis. Previous studies demonstrated that the synthetic triterpenoid, CDDO-Imidazolide (CDDO-Im) induced cell cycle arrest and apoptosis in triple-negative breast cancer. Since a small subpopulation of cancer stem cells has been suggested to be responsible for drug resistance and metastasis of tumors, our present study determined whether the effects of CDDO-Im in triple-negative breast cancer are due to the inhibition of a cancer stem cell subpopulation. CDDO-Im treatment markedly induced cell cycle arrest at G2/M-phase and apoptosis in the triple-negative breast cancer cell lines, SUM159 and MDA-MB-231. Because SUM159 cells were more sensitive to CDDO-Im than MDA-MB-231 cells, the effects of CDDO-Im on the cancer stem cell subpopulation were further investigated in SUM159 cells. SUM159 cells formed tumorspheres in culture, and the cancer stem cell subpopulation, CD24−/EpCAM+ cells, was markedly enriched in SUM159 tumorspheres. The CD24−/EpCAM+ cells in SUM159 tumorspheres were significantly inhibited by CDDO-Im treatment. CDDO-Im also significantly decreased sphere forming efficiency and tumorsphere size in both primary and secondary sphere cultures. PCR array of stem cell signaling genes showed that expression levels of many key molecules in the stem cell signaling pathways, such as Notch, TGF-β/Smad, Hedgehog and Wnt, were significantly down-regulated by CDDO-Im in SUM159 tumorspheres. Protein levels of Notch receptors (c-Notch1, Notch1 and Notch3), TGF-β/Smad (pSmad2/3) and Hedgehog downstream effectors (GLI1) also were markedly reduced by CDDO-Im. In conclusion, the present study demonstrates that the synthetic triterpenoid, CDDO-Im, is a potent anti-cancer agent against triple-negative breast cancer cells by targeting the cancer stem cell subpopulation. PMID:25229616

β-arrestins negatively control human adrenomedullin type 1-receptor internalization.

PubMed

Kuwasako, Kenji; Kitamura, Kazuo; Nagata, Sayaka; Sekiguchi, Toshio; Danfeng, Jiang; Murakami, Manabu; Hattori, Yuichi; Kato, Johji

2017-05-27

Adrenomedullin (AM) is a potent hypotensive peptide that exerts a powerful variety of protective effects against multiorgan damage through the AM type 1 receptor (AM 1 receptor), which consists of the calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 2 (RAMP2). Two β-arrestin (β-arr) isoforms, β-arr-1 and β-arr-2, play a central role in the agonist-induced internalization of many receptors for receptor resensitization. Notably, β-arr-biased agonists are now being tested in phase II clinical trials, targeting acute pain and acute heart failure. Here, we examined the effects of β-arr-1 and β-arr-2 on human AM 1 receptor internalization. We constructed a V5-tagged chimera in which the cytoplasmic C-terminal tail (C-tail) of CLR was replaced with that of the β 2 -adrenergic receptor (β 2 -AR), and it was transiently transfected into HEK-293 cells that stably expressed RAMP2. The cell-surface expression and internalization of the wild-type or chimeric receptor were quantified by flow cytometric analysis. The [ 125 I]AM binding and the AM-induced cAMP production of these receptors were also determined. Surprisingly, the coexpression of β-arr-1 or -2 resulted in significant decreases in AM 1 receptor internalization without affecting AM binding and signaling prior to receptor internalization. Dominant-negative (DN) β-arr-1 or -2 also significantly decreased AM-induced AM 1 receptor internalization. In contrast, the AM-induced internalization of the chimeric AM 1 receptor was markedly augmented by the cotransfection of β-arr-1 or -2 and significantly reduced by the coexpression of DN-β-arr-1 or -2. These results were consistent with those seen for β 2 -AR. Thus, both β-arrs negatively control AM 1 receptor internalization, which depends on the C-tail of CLR. Copyright © 2017 Elsevier Inc. All rights reserved.

Negative affect impairs associative memory but not item memory.

PubMed

Bisby, James A; Burgess, Neil

2013-12-17

The formation of associations between items and their context has been proposed to rely on mechanisms distinct from those supporting memory for a single item. Although emotional experiences can profoundly affect memory, our understanding of how it interacts with different aspects of memory remains unclear. We performed three experiments to examine the effects of emotion on memory for items and their associations. By presenting neutral and negative items with background contexts, Experiment 1 demonstrated that item memory was facilitated by emotional affect, whereas memory for an associated context was reduced. In Experiment 2, arousal was manipulated independently of the memoranda, by a threat of shock, whereby encoding trials occurred under conditions of threat or safety. Memory for context was equally impaired by the presence of negative affect, whether induced by threat of shock or a negative item, relative to retrieval of the context of a neutral item in safety. In Experiment 3, participants were presented with neutral and negative items as paired associates, including all combinations of neutral and negative items. The results showed both above effects: compared to a neutral item, memory for the associate of a negative item (a second item here, context in Experiments 1 and 2) is impaired, whereas retrieval of the item itself is enhanced. Our findings suggest that negative affect impairs associative memory while recognition of a negative item is enhanced. They support dual-processing models in which negative affect or stress impairs hippocampal-dependent associative memory while the storage of negative sensory/perceptual representations is spared or even strengthened.

Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis.

PubMed

Weichhaus, Michael; Segaran, Prabu; Renaud, Ashleigh; Geerts, Dirk; Connelly, Linda

2014-10-01

Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor (TNF) receptor superfamily that has been well characterized as a negative regulator of bone remodeling. OPG is also expressed in human breast cancer tissues and cell lines. In vitro studies suggest that OPG exerts tumor-promoting effects by binding to TNF-related apoptosis inducing ligand (TRAIL), thereby preventing induction of apoptosis. However, the in vivo effect of OPG expression by primary breast tumors has not been characterized. We knocked down OPG expression in MDA-MB-231 and MDA-MB-436 human breast cancer cells using shRNA and siRNA to investigate impact on metastasis in the chick embryo model. We observed a reduction in metastasis with OPG knockdown cells. We found that lowering OPG expression did not alter sensitivity to TRAIL-induced apoptosis; however, the OPG knockdown cells had a reduced level of invasion. In association with this we observed reduced expression of the proteases Cathepsin D and Matrix Metalloproteinase-2 upon OPG knockdown, indicating that OPG may promote metastasis via modulation of protease expression and invasion. We conclude that OPG has a metastasis-promoting effect in breast cancer cells. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Declining fertility and economic well-being: do education and health ride to the rescue?

PubMed Central

Prettner, Klaus; Bloom, David E.; Strulik, Holger

2015-01-01

It is widely argued that declining fertility slows the pace of economic growth in industrialized countries through its negative effect on labor supply. There are, however, theoretical arguments suggesting that the effect of falling fertility on effective labor supply can be offset by associated behavioral changes. We formalize these arguments by setting forth a dynamic consumer optimization model that incorporates endogenous fertility as well as endogenous education and health investments. The model shows that a fertility decline induces higher education and health investments that are able to compensate for declining fertility under certain circumstances. We assess the theoretical implications by investigating panel data for 118 countries over the period 1980 to 2005 and show that behavioral changes partly mitigate the negative impact of declining fertility on effective labor supply. PMID:26388677

Gender differences in negative affect during acute tobacco abstinence differ between African American and White adult cigarette smokers.

PubMed

Pang, Raina D; Bello, Mariel S; Liautaud, Madalyn M; Weinberger, Andrea H; Leventhal, Adam M

2018-06-15

Prior studies have found heightened negative affect following tobacco abstinence in women compared to men. However, experimental work addressing whether these findings generalize across racial groups is scarce. The current study investigated whether race (Non-Hispanic White vs. Non-Hispanic African American) moderated gender differences in abstinence-induced negative affect and smoking behavior. Data were collected from 2010 to 2017 from two separate laboratory studies investigating experimentally manipulated tobacco abstinence. Following a baseline session, adult daily smokers (10 cigarettes per day; women: n=297, 83.8% Non-Hispanic African American; men: n=492, 86.2% Non-Hispanic African American) attended two counterbalanced lab sessions (16 hours abstinent vs. non-abstinent) and completed self-report measures of negative affect followed by a laboratory analogue smoking reinstatement task. We found a gender race interaction for several negative affect states and composite negative affect (ßs=-.12 to -.16, ps<.05). Analyses stratified by race showed that Non-Hispanic White women compared to Non-Hispanic White men exhibited greater abstinence-induced increases in anger, anxiety, and composite negative affect (ßs=-.20 to -.29, ps<.05). No significant gender differences in abstinence-induced negative affect were found for Non-Hispanic African American smokers (ßs=.00 to -.04, ps>.05). These findings suggest that negative affect during acute tobacco abstinence may be a clinically important and intervenable factor that can inform cessation interventions specifically for Non-Hispanic White women smokers. Further empirical exploration of mechanisms underlying interactions of gender and race in tobacco addiction may benefit smoking cessation efforts in Non-Hispanic African American women smokers. The current study contributes to a scant body of research examining the intersectional influence of race and gender on abstinence-induced negative affect-a central, motivationally prepotent feature of tobacco withdrawal. Using a laboratory-based design to experimentally manipulate abstinence, we provide evidence of a gender race interaction on negative affect-related withdrawal. Our findings suggest that gender differences in abstinence-induced negative affect observed among Non-Hispanic White smokers may not generalize to Non-Hispanic African American smokers, highlighting the need for future work to address potential mechanisms underlying the racially discrepant impact of gender on affective tobacco withdrawal.

Subliminal presentation of emotionally negative vs positive primes increases the perceived beauty of target stimuli.

PubMed

Era, Vanessa; Candidi, Matteo; Aglioti, Salvatore Maria

2015-11-01

Emotions have a profound influence on aesthetic experiences. Studies using affective priming procedures demonstrate, for example, that inducing a conscious negative emotional state biases the perception of abstract stimuli towards the sublime (Eskine et al. Emotion 12:1071-1074, 2012. doi: 10.1037/a0027200). Moreover, subliminal happy facial expressions have a positive impact on the aesthetic evaluation of abstract art (Flexas et al. PLoS ONE 8:e80154, 2013). Little is known about how emotion influences aesthetic perception of non-abstract, representational stimuli, especially those that are particularly relevant for social behaviour, like human bodies. Here, we explore whether the subliminal presentation of emotionally charged visual primes modulates the explicit subjective aesthetic judgment of body images. Using a forward/backward masking procedure, we presented subliminally positive and negative, arousal-matched, emotional or neutral primes and measured their effect on the explicit evaluation of perceived beauty (high vs low) and emotion (positive vs negative) evoked by abstract and body images. We found that negative primes increased subjective aesthetic evaluations of target bodies or abstract images in comparison with positive primes. No influence of primes on the emotional dimension of the targets was found, thus ruling out an unspecific arousal effect and strengthening the link between emotional valence and aesthetic appreciation. More specifically, that subliminal negative primes increase beauty ratings compared to subliminal positive primes indicates a clear link between negative emotions and positive aesthetic evaluations and vice versa, suggesting a possible link between negative emotion and the experience of sublime in art. The study expands previous research by showing the effect of subliminal negative emotions on the subjective aesthetic evaluation not only of abstract but also of body images.

Overexpression of SKP2 Inhibits the Radiation-Induced Bystander Effects of Esophageal Carcinoma.

PubMed

Wang, Xiao-Chun; Zhang, Tie-Jun; Guo, Zi-Jian; Xiao, Chang-Yan; Ding, Xiao-Wen; Fang, Fang; Sheng, Wen-Tao; Shu, Xu; Li, Jue

2017-02-06

To investigate the effects of S-phase kinase protein 2 (SKP2) expression on the radiation induced bystander effect (RIBE) in esophageal cancer (EC) cells. Western blot was used to detect the levels of SKP2, Rad51, and Ku70 in EC cells. Positive transfection, RNAi, micronucleus (MN), and γ-H2AX focus formation assay were used to investigate the effects of SKP2 on RIBE induced by irradiated cells. We found a significant negative correlation between SKP2 expression and MN frequency ( p < 0.05) induced by RIBE. The results were further confirmed by positive transfection, RNAi, and rescue experiments.γ-H2AX focus formation assay results indicated that overexpression of SKP2 in the irradiated cells inhibited the DNA damage of RIBE cells. However, when SKP2 expression decreased in irradiated cells, the DNA damage of RIBE cells increased. Increased or decreased expression levels of SKP2 had effects on Rad51 expression under the conditions of RIBE. These results showed, for the first time, that SKP2 expression can inhibit RIBE of EC cells. The mechanism may function, at least partly, through the regulation of Rad51 in the ability to repair DNA damage.

Cluster synchronization induced by one-node clusters in networks with asymmetric negative couplings

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

Zhang, Jianbao; Ma, Zhongjun, E-mail: mzj1234402@163.com; Zhang, Gang

2013-12-15

This paper deals with the problem of cluster synchronization in networks with asymmetric negative couplings. By decomposing the coupling matrix into three matrices, and employing Lyapunov function method, sufficient conditions are derived for cluster synchronization. The conditions show that the couplings of multi-node clusters from one-node clusters have beneficial effects on cluster synchronization. Based on the effects of the one-node clusters, an effective and universal control scheme is put forward for the first time. The obtained results may help us better understand the relation between cluster synchronization and cluster structures of the networks. The validity of the control scheme ismore » confirmed through two numerical simulations, in a network with no cluster structure and in a scale-free network.« less

Induced attitude change on online gaming among adolescents: an application of the less-leads-to-more effect.

PubMed

Chiou, Wen-Bin

2008-04-01

The negative impact of Internet use on adolescents has received much popular attention and has also become a popular research topic. How to induce adolescent players to change their attitudes toward online gaming is one of the most important issues in online gaming addiction. The present study is based on the less-leads-to-more effect of dissonance theory. Experimental research was conducted to examine the effects of rewards and decision freedom on attitude change toward online gaming among adolescents considered at risk for addiction. The results supported predictions based on external justification in dissonance theory. Specifically, fewer rewards produced greater attitude change toward online gaming in the condition of personal freedom of choice after participants exhibited attitude-discrepant behavior. However, the less-leads-to-more effect was not prominent in the condition without personal freedom of choice. Adopting a reward strategy to induce game players to disengage online gaming is discussed.

Prolyl Hydroxylase EGLN3 Regulates Skeletal Myoblast Differentiation through an NF-κB-dependent Pathway

PubMed Central

Fu, Jian; Taubman, Mark B.

2010-01-01

The egg-laying abnormal-9 (EGLN) prolyl hydroxylases have been shown to regulate the stability and thereby the activity of the α subunits of hypoxia-inducible factor (HIF) through its ability to catalyze their hydroxylation. We have previously shown that EGLN3 promotes differentiation of C2C12 skeletal myoblasts. However, the mechanism underlying this effect remains to be fully elucidated. Here, we report that exposure of C2C12 cells to dimethyl oxalylglycine (DMOG), desferrioxamine, and hypoxia, all inhibitors of prolyl hydroxylase activity, led to repression of C2C12 myogenic differentiation. Inactivation of HIF by expression of a HIF dominant-negative mutant or deletion of HIF-1α by RNA interference did not affect the inhibitory effect of DMOG, suggesting that the effect of DMOG is HIF-independent. Pharmacologic inactivation of EGLN3 hydroxylase resulted in activation of the canonical NF-κB pathway. The inhibitory effect of DMOG on myogenic differentiation was markedly impaired in C2C12 cells expressing a dominant-negative mutant of IκBα. Exogenous expression of wild-type EGLN3, but not its catalytically inactive mutant, significantly inhibited NF-κB activation induced by overexpressed TRAF2 or IκB kinase 2. In contrast, deletion of EGLN3 by small interfering RNAs led to activation of NF-κB. These data suggest that EGLN3 is a negative regulator of NF-κB, and its prolyl hydroxylase activity is required for this effect. Furthermore, wild-type EGLN3, but not its catalytically inactive mutant, potentiated myogenic differentiation. This study demonstrates a novel role for EGLN3 in the regulation of NF-κB and suggests that it is involved in mediating myogenic differentiation, which is HIF-independent. PMID:20089853

The effects of trait impulsivity on proactive and reactive interference control.

PubMed

Xiang, Ling; Chen, Yan; Chen, Antao; Zhang, Fenghua; Xu, Fuming; Wang, Baoxi

2018-02-01

The current study used event-related brain potentials (ERPs) to explore whether self-reported trait impulsivity in healthy individuals might be differentially related to proactive and reactive interference control. Participants with high and low impulsivity (HI and LI, respectively) performed a modified version of the prime-target interference task. Proactive interference control was induced in the mostly incongruent (MI) context and reactive interference control was induced in the mostly congruent (MC) context. Although the behavioral data revealed no difference between HI and LI individuals in terms of the interference effects (incongruent - congruent) under both contexts, the ERP results showed that impulsivity has a different influence on the interference effects under different task contexts. In the MC context, the interference effects on the medial frontal negativity (MFN) and the negative sustained potential (N-SP) were greater, while that on the positive sustained potential (P-SP) were smaller in the HI compared to those in the LI group. This suggests that high levels of impulsivity might be associated with a reduced efficiency of the processes supporting reactive control to resolve interference when interference is not expected. In contrast, the three ERP indices (MFN, P-SP, and N-SP) of interference processing in the MI context were insensitive to variations in impulsivity. This suggests that HI individuals might be as effective as LI individuals in recruiting proactive control for sustained active maintenance of task goals to anticipate and prevent interference throughout the experimental blocks where interference occurs frequently. In conclusion, these results indicate that impulsivity has a more negative influence on reactive interference control than on proactive interference control. Copyright © 2017. Published by Elsevier B.V.

Effects of acute MDMA intoxication on mood and impulsivity: role of the 5-HT2 and 5-HT1 receptors.

PubMed

van Wel, Janelle H P; Kuypers, Kim P C; Theunissen, Eef L; Bosker, Wendy M; Bakker, Katja; Ramaekers, Johannes G

2012-01-01

MDMA induces positive mood and increases impulse control during intoxication, but only a few studies on the neuropharmacological mechanisms underlying these processes have been conducted. It was hypothesized that pretreatment with 5-HT(1) and 5-HT(2) receptor blockers would prevent MDMA effects on mood and impulsivity. Subjects (N = 17) participated in a double-blind, placebo controlled, within-subject design involving 6 experimental conditions consisting of pretreatment (T1) and treatment (T2). T1 preceded T2 by 30 minutes. T1-T2 combinations were: placebo-placebo, 20 mg pindolol-placebo, 50 mg ketanserin-placebo, placebo-75 mg MDMA, 20 mg pindolol-75 mg MDMA and 50 mg ketanserin-75 g MDMA. Subjects completed a Profile of Mood States (POMS) questionnaire and several impulsivity tasks (Stop signal task, Matching familiar figures task, Cue dependent reversal learning task) at 1.5 hrs post-treatment. MDMA alone increased both positive (vigor, arousal, friendliness, elation, positive mood) and negative affect (anxiety, confusion) as assessed by the POMS questionnaire. MDMA also increased stop reaction time in the Stop signal task and reaction time in the Matching familiar figures task. Pretreatment with ketanserin blocked MDMA effects on positive affect, but not negative affect. Ketanserin did not influence the effects of MDMA on impulsivity. Pindolol did not interact with MDMA on any of the measures. In conclusion, 5-HT(2) receptors mediate positive moods induced by MDMA but not negative moods or impulsivity. 5-HT(1) receptors do not appear to be involved in MDMA effects on mood and impulse control. Nederlands Trial Register NTR2352.

Effects of Acute MDMA Intoxication on Mood and Impulsivity: Role of the 5-HT2 and 5-HT1 Receptors

PubMed Central

van Wel, Janelle H. P.; Kuypers, Kim P. C.; Theunissen, Eef L.; Bosker, Wendy M.; Bakker, Katja; Ramaekers, Johannes G.

2012-01-01

MDMA induces positive mood and increases impulse control during intoxication, but only a few studies on the neuropharmacological mechanisms underlying these processes have been conducted. It was hypothesized that pretreatment with 5-HT1 and 5-HT2 receptor blockers would prevent MDMA effects on mood and impulsivity. Subjects (N = 17) participated in a double-blind, placebo controlled, within-subject design involving 6 experimental conditions consisting of pretreatment (T1) and treatment (T2). T1 preceded T2 by 30 minutes. T1–T2 combinations were: placebo-placebo, 20 mg pindolol-placebo, 50 mg ketanserin-placebo, placebo-75 mg MDMA, 20 mg pindolol-75 mg MDMA and 50 mg ketanserin-75 g MDMA. Subjects completed a Profile of Mood States (POMS) questionnaire and several impulsivity tasks (Stop signal task, Matching familiar figures task, Cue dependent reversal learning task) at 1.5 hrs post-treatment. MDMA alone increased both positive (vigor, arousal, friendliness, elation, positive mood) and negative affect (anxiety, confusion) as assessed by the POMS questionnaire. MDMA also increased stop reaction time in the Stop signal task and reaction time in the Matching familiar figures task. Pretreatment with ketanserin blocked MDMA effects on positive affect, but not negative affect. Ketanserin did not influence the effects of MDMA on impulsivity. Pindolol did not interact with MDMA on any of the measures. In conclusion, 5-HT2 receptors mediate positive moods induced by MDMA but not negative moods or impulsivity. 5-HT1 receptors do not appear to be involved in MDMA effects on mood and impulse control. Trial Registration Nederlands Trial Register NTR2352 PMID:22808116

Arbuscular mycorrhizae alleviate negative effects of zinc oxide nanoparticle and zinc accumulation in maize plants--A soil microcosm experiment.

PubMed

Wang, Fayuan; Liu, Xueqin; Shi, Zhaoyong; Tong, Ruijian; Adams, Catharine A; Shi, Xiaojun

2016-03-01

ZnO nanoparticles (NPs) are considered an emerging contaminant when in high concentration, and their effects on crops and soil microorganisms pose new concerns and challenges. Arbuscular mycorrhizal (AM) fungi (AMF) form mutualistic symbioses with most vascular plants, and putatively contribute to reducing nanotoxicity in plants. Here, we studied the interactions between ZnO NPs and maize plants inoculated with or without AMF in ZnO NPs-spiked soil. ZnO NPs had no significant adverse effects at 400 mg/kg, but inhibited both maize growth and AM colonization at concentrations at and above 800 mg/kg. Sufficient addition of ZnO NPs decreased plant mineral nutrient acquisition, photosynthetic pigment concentrations, and root activity. Furthermore, ZnO NPs caused Zn concentrations in plants to increase in a dose-dependent pattern. As the ZnO NPs dose increased, we also found a positive correlation with soil diethylenetriaminepentaacetic acid (DTPA)-extractable Zn. However, AM inoculation significantly alleviated the negative effects induced by ZnO NPs: inoculated-plants experienced increased growth, nutrient uptake, photosynthetic pigment content, and SOD activity in leaves. Mycorrhizal plants also exhibited decreased ROS accumulation, Zn concentrations and bioconcentration factor (BCF), and lower soil DTPA-extractable Zn concentrations at high ZnO NPs doses. Our results demonstrate that, at high contamination levels, ZnO NPs cause toxicity to AM symbiosis, but AMF help alleviate ZnO NPs-induced phytotoxicity by decreasing Zn bioavailability and accumulation, Zn partitioning to shoots, and ROS production, and by increasing mineral nutrients and antioxidant capacity. AMF may play beneficial roles in alleviating the negative effects and environmental risks posed by ZnO NPs in agroecosystems. Copyright © 2015 Elsevier Ltd. All rights reserved.

ONO-8590580, a Novel GABAAα5 Negative Allosteric Modulator Enhances Long-Term Potentiation and Improves Cognitive Deficits in Preclinical Models.

PubMed

Kawaharada, Soichi; Nakanishi, Miki; Nakanishi, Nobuto; Hazama, Keisuke; Higashino, Masato; Yasuhiro, Tetsuya; Lewis, Arwel; Clark, Gary S; Chambers, Mark S; Maidment, Scott A; Katsumata, Seishi; Kaneko, Shuji

2018-07-01

GABA A receptors containing α 5 subunits (GABA A α 5) are highly expressed in the hippocampus and negatively involved in memory processing, as shown by the fact that GABA A α 5-deficient mice show higher hippocampus-dependent performance than wild-type mice. Accordingly, small-molecule GABA A α 5 negative allosteric modulators (NAMs) are known to enhance spatial learning and memory in rodents. Here we introduce a new, orally available GABA A α 5 NAM that improves hippocampal functions. ONO-8590580 [1-(cyclopropylmethyl)-5-fluoro-4-methyl- N -[5-(1-methyl-1H-imidazol-4-yl)-2-pyridinyl]-1H-benzimidazol-6-amine] binds to the benzodiazepine binding sites on recombinant human α 5-containing GABA A receptors with a K i of 7.9 nM, and showed functionally selective GABA A α 5 NAM activity for GABA-induced Cl - channel activity with a maximum 44.4% inhibition and an EC 50 of 1.1 nM. In rat hippocampal slices, tetanus-induced long-term potentiation of CA1 synapse response was significantly augmented in the presence of 300 nM ONO-8590580. Orally administered ONO-8590580 (1-20 mg/kg) dose-dependently occupied hippocampal GABA A α 5 in a range of 40%-90% at 1 hour after intake. In the rat passive avoidance test, ONO-8590580 (3-20 mg/kg, by mouth) significantly prevented (+)-MK-801 hydrogen maleate (MK-801)-induced memory deficit. In addition, ONO-8590580 (20 mg/kg, p.o.) was also effective in improving the cognitive deficit induced by scopolamine and MK-801 in the rat eight-arm radial maze test with equal or greater activity than 0.5 mg/kg donepezil. No anxiogenic-like or proconvulsant effect was associated with ONO-8590580 at 20 mg/kg p.o. in the elevated plus maze test or pentylenetetrazole-induced seizure test, respectively. In sum, ONO-8590580 is a novel GABA A α 5 NAM that enhances hippocampal memory function without an anxiogenic or proconvulsant risk. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Repetitive transcranial magnetic stimulation modulates the impact of a negative mood induction

PubMed Central

Lacomblé, Lylis; Meyer, Thomas; Schutter, Dennis J.L.G.; Gielkens, Tom; Becker, Eni S.; Tendolkar, Indira; van Eijndhoven, Philip

2017-01-01

Abstract High frequency repetitive Transcranial Magnetic Stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been found to alleviate depressive symptoms. However, the mechanisms driving these effects are still poorly understood. In the current study, we tested the idea that this intervention protects against negative mood shifts following emotional provocation. We furthermore explored changes in EEG activity (frontal alpha asymmetry) and effects on attentional processing (emotional Stroop). To this end, 23 healthy individuals participated in two sessions separated by one week, whereby they once received 15 min of 10Hz rTMS stimulation (1500 pulses) at 110% of the individual motor threshold, and once sham stimulation. Then, negative mood was induced using sad movie clips. The results revealed a significantly stronger mood decline following rTMS compared to sham stimulation. No changes were observed in frontal alpha asymmetry and attentional processing. Our findings are at odds with the view that high frequency rTMS over the left DLPFC directly protects against the induction of negative mood, but rather suggest that it enhances the effects of emotional provocation. Possibly, in healthy young individuals, this stimulation protocol heightens susceptibility to mood induction procedures in general. PMID:28008080

Origin of negative resistance in anion migration controlled resistive memory

NASA Astrophysics Data System (ADS)

Banerjee, Writam; Wu, Facai; Hu, Yuan; Wu, Quantan; Wu, Zuheng; Liu, Qi; Liu, Ming

2018-03-01

Resistive random access memory (RRAM) is one of the most promising emerging nonvolatile technologies for the futuristic memory devices. Resistive switching behavior often shows negative resistance (NR), either voltage controlled or current controlled. In this work, the origin of a current compliance dependent voltage controlled NR effect during the resetting of anion migration based RRAM devices is discussed. The N-type voltage controlled NR is a high field driven phenomena. The current conduction within the range of a certain negative voltage is mostly dominated by space charge limited current. But with the higher negative voltage, a field induced tunneling effect is generated in the NR region. The voltage controlled NR is strongly dependent on the compliance current. The area independent behavior indicates the filamentary switching. The peak to valley ratio (PVR) is > 5. The variation of PVR as a function of the conduction band offset is achieved. Compared to other reported works, based on the PVR, it is possible to distinguish the RRAM types. Generally, due to the higher electric field effect on the metallic bridge during RESET, the electrochemical metallization type RRAM shows much higher PVR than the valance change type RRAM.

Visible-light-induced instability in amorphous metal-oxide based TFTs for transparent electronics

NASA Astrophysics Data System (ADS)

Ha, Tae-Jun

2014-10-01

We investigate the origin of visible-light-induced instability in amorphous metal-oxide based thin film transistors (oxide-TFTs) for transparent electronics by exploring the shift in threshold voltage (Vth). A large hysteresis window in amorphous indium-gallium-zinc-oxide (a-IGZO) TFTs possessing large optical band-gap (≈3 eV) was observed in a visible-light illuminated condition whereas no hysteresis window was shown in a dark measuring condition. We also report the instability caused by photo irradiation and prolonged gate bias stress in oxide-TFTs. Larger Vth shift was observed after photo-induced stress combined with a negative gate bias than the sum of that after only illumination stress and only negative gate bias stress. Such results can be explained by trapped charges at the interface of semiconductor/dielectric and/or in the gate dielectric which play a role in a screen effect on the electric field applied by gate voltage, for which we propose that the localized-states-assisted transitions by visible-light absorption can be responsible.

Saturated fatty acid palmitate negatively regulates autophagy by promoting ATG5 protein degradation in meniscus cells.

PubMed

Mallik, Aritra; Yammani, Raghunatha R

2018-07-20

Obesity and associated metabolic factors are major risk factors for the development of osteoarthritis. Previously, we have shown that the free fatty acid palmitate induces endoplasmic reticulum (ER) stress and induces apoptosis in meniscus cells. However, the molecular mechanisms involved in these effects are not clearly understood. In our current study, we found that palmitate inhibits autophagy by modulating the protein levels of autophagy-related genes-5 (ATG5) that is associated with decreased lipidation of LC3 and increased activation of cleaved caspase 3. Pretreatment of meniscus cells with 4-phenyl butyric acid, a small molecule chemical chaperone that alleviates ER stress, or with MG-132, a proteasome inhibitor, restored normal levels of ATG5 and autophagosome formation, and decreased expression of cleaved caspase 3. Thus, our data suggest that palmitate downregulates autophagy in meniscus cells by degrading ATG5 protein via ER-associated protein degradation, and thus promotes apoptosis. This is the first study to demonstrate that palmitate-induced endoplasmic reticulum stress negatively regulates autophagy. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Light-induced defects in hybrid lead halide perovskite

NASA Astrophysics Data System (ADS)

Sharia, Onise; Schneider, William

One of the main challenges facing organohalide perovskites for solar application is stability. Solar cells must last decades to be economically viable alternatives to traditional energy sources. While some causes of instability can be avoided through engineering, light-induced defects can be fundamentally limiting factor for practical application of the material. Light creates large numbers of electron and hole pairs that can contribute to degradation processes. Using ab initio theoretical methods, we systematically explore first steps of light induced defect formation in methyl ammonium lead iodide, MAPbI3. In particular, we study charged and neutral Frenkel pair formation involving Pb and I atoms. We find that most of the defects, except negatively charged Pb Frenkel pairs, are reversible, and thus most do not lead to degradation. Negative Pb defects create a mid-gap state and localize the conduction band electron. A minimum energy path study shows that, once the first defect is created, Pb atoms migrate relatively fast. The defects have two detrimental effects on the material. First, they create charge traps below the conduction band. Second, they can lead to degradation of the material by forming Pb clusters.

Heijiangdan ointment relieves oxidative stress from radiation dermatitis induced by (60)Co γ-ray in mice.

PubMed

Yang, Lin; Yu, Ming-wei; Wang, Xiao-min; Zhang, Yi; Yang, Guo-wang; Luo, Xiao-qin; Peng, Rui-yun; Gao, Ya-bing; Zhao, Li; Wang, Li-feng

2016-02-01

To investigate the effects of Heijiangdan Ointment ( HJD) on oxidative stress in (60)Co γ-ray radiation-induced dermatitis in mice. Female Wistar mice with grade 4 radiation dermatitis induced by (60)Co γ-rays were randomly divided into four groups (n=12 per group); the HJD-treated, recombinant human epidermal growth factor (rhEGF)-treated, Trolox-treated, and untreated groups, along with a negative control group. On the 11th and 21st days after treatment, 6 mice in each group were chosen for evaluation. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and lactate dehydrogenase (LDH) were detected using spectrophotometric methods. The fibroblast mitochondria were observed by transmission electron microscopy (TEM). The expressions of fibroblast growth factor 2 (FGF-2) and transforming growth factor β1 (TGF-β1) were analyzed by western blot. Compared with the untreated group, the levels of SOD, MDA and LDH, on the 11th and 21st days after treatment showed significant difference (P<0.05). TEM analysis indicated that fibroblast mitochondria in the untreated group exhibited swelling and the cristae appeared fractured, while in the HJD group, the swelling of mitochondria was limited and the rough endoplasmic reticulum appeared more relaxed. The expressions of FGF-2 and TGF-β1 increased in the untreated group compared with the negative control group (P<0.05). After treatment, the expression of FGF-2, rhEGF and Trolox in the HJD group were significantly increased compared with the untreated group (P<0.05), or compared with the negative control group (P<0.05). The expression of TGF-β1 showed significant difference between untreated and negative control groups (P<0.05). HJD and Trolox increased the level of TGF-β1 and the difference was marked as compared with the untreated and negative control groups (P<0.05). HJD relieves oxidative stress-induced injury, increases the antioxidant activity, mitigates the fibroblast mitochondrial damage, up-regulates the expression of growth factor, and promotes mitochondrial repair in mice.

Inducing Negative Affect Increases the Reward Value of Appetizing Foods in Dieters

PubMed Central

Wagner, Dylan D.; Boswell, Rebecca G.; Kelley, William M.; Heatherton, Todd F.

2013-01-01

Experiencing negative affect frequently precedes lapses in self-control for dieters, smokers, and drug addicts. Laboratory research has similarly shown that inducing negative emotional distress increases the consumption of food or drugs. One hypothesis for this finding is that emotional distress sensitizes the brain’s reward system to appetitive stimuli. Using functional neuroimaging, we demonstrate that inducing negative affect in chronic dieters increases activity in brain regions representing the reward value of appetitive stimuli when viewing appetizing food cues. Thirty female chronic dieters were randomly assigned to receive either a negative (n = 15) or neutral mood induction (n = 15) immediately followed by exposure to images of appetizing foods and natural scenes during functional magnetic resonance imaging (fMRI). Compared to chronic dieters in a neutral mood, those receiving a negative mood induction showed increased activity in the orbitofrontal cortex to appetizing food images. In addition, activity to food images in the orbitofrontal cortex and ventral striatum was correlated with individual differences in the degree to which the negative mood induction decreased participants’ self-esteem. These findings suggest that distress sensitizes the brain’s reward system to appetitive cues thereby offering a mechanism for the oft-observed relationship between negative affect and disinhibited eating. PMID:22524295

Photodetachment process for beam neutralization

DOEpatents

Fink, Joel H. [Livermore, CA; Frank, Alan M. [Livermore, CA

1979-02-20

A process for neutralization of accelerated ions employing photo-induced charge detachment. The process involves directing a laser beam across the path of a negative ion beam such as to effect photodetachment of electrons from the beam ions. The frequency of the laser beam employed is selected to provide the maximum cross-section for the photodetachment process.

Thyroid Hormone Changes during Military Field Operations: Effects of Cold Exposure in the Arctic.

DTIC Science & Technology

1991-12-20

reasons; however, they primarily appear related to the hypocaloric states induced by a negative energy balance, stress reactivity of the endocrine...physical strain and sleep deprivation, and the influence of a high calorie diet . Eur J Appl Physiol 49:343-348. 17. Opstad PK, Aakvaag A (1983). The

Integrated communication and control systems. II - Design considerations

NASA Technical Reports Server (NTRS)

Ray, Asok; Halevi, Yoram

1988-01-01

The ICCS design issues for nonperiodic and stochastic delays are addressed and the framework for alternative design procedures is outlined. The impact of network-induced delays on system stability is investigated and their physical significance is demonstrated using a simulation. The negative effects of vacant sampling and message rejection at the controller are demonstrated.

Novel Strategies for the Treatment of Estrogen Receptor-Negative Breast Cancer

DTIC Science & Technology

2007-10-01

quercetin on benzo[a]pyrene induced DNA damage in HepG2 cells as measured by the comet assay” at the Annual Intermountain Meeting of the American Society...Anti-genotoxic effects of Garlic extract and Quercetin as Measured by the Comet Assay, The Journal of the Intermountain Branch of the American

Parvalbumin Interneurons of Central Amygdala Regulate the Negative Affective States and the Expression of Corticotrophin-Releasing Hormone During Morphine Withdrawal

PubMed Central

Wang, Li; Shen, Minjie; Jiang, Changyou

2016-01-01

Background: The central nucleus of the amygdala (CeA) is a crucial component of the neuronal circuitry mediating aversive emotion. Its role in the negative affective states during drug withdrawal includes changes in opioidergic, GABAergic, and corticotropin-releasing factor neurotransmission. However, the modulation of the neurobiological interconnectivity in the CeA and its effects in the negative reinforcement of drug dependents are poorly understood. Method: We performed electrophysiological recordings to assess the membrane excitability of parvalbumin (PV)+ interneurons in the CeA during chronic morphine withdrawal. We tested the morphine withdrawal–induced negative affective states, such as the aversive (assessed by conditioned place aversion), anxiety (assessed by elevated plus maze), and anhedonic-like (assessed by saccharin preference test) behaviors, as well as the mRNA level of corticotropin-releasing hormone (CRH) via optogenetic inhibition or activation of PV+ interneurons in the CeA. Result: Chronic morphine withdrawal increased the firing rate of CeA PV+ interneurons. Optogenetic inhibition of the activity of CeA PV+ interneurons attenuated the morphine withdrawal–induced negative affective states, such as the aversive, anxiety, and anhedonic-like behaviors, while direct activation of CeA PV+ interneurons could trigger those negative affective-like behaviors. Optogenetic inhibition of the CeA PV+ interneurons during the morphine withdrawal significantly attenuated the elevated CRH mRNA level in the CeA. Conclusion: The activity of PV+ interneurons in the CeA was up-regulated during chronic morphine withdrawal. The activation of PV+ interneurons during morphine withdrawal was crucial for the induction of the negative emotion and the up-regulation of CRH mRNA levels in the CeA. PMID:27385383

Relations between conspecific density and effects of ultraviolet-b radiation on tadpole size in the striped marsh frog.

PubMed

Mitchell, Toby; Alton, Lesley A; White, Craig R; Franklin, Craig E

2012-12-01

Global increases in ultraviolet-B radiation (UVBR) associated with stratospheric ozone depletion are potentially contributing to the decline of numerous amphibian species around the world. Exposure to UVBR alone reduces survival and induces a range of sublethal effects in embryonic and larval amphibians. When additional environmental stressors are present, UVBR can have compounding negative effects. Thus, examination of the effects of UVBR in the absence of other stressors may substantially underestimate its potential to affect amphibians in natural habitats. We examined the independent and interactive effects of increased UVBR and high conspecific density would have embryonic and larval striped marsh frogs (Limnodynastes peronii). We exposed individuals to a factorial combination of low and high UVBR levels and low, medium, and high densities of striped marsh frog tadpoles. The response variables were time to hatching, hatching success, posthatch survival, burst-swimming performance of tadpoles (maximum instantaneous swim speed following an escape response), and size and morphology of tadpoles. Consistent with results of previous studies, we found that exposure to UVBR alone increased the time to hatching of embryos and reduced the burst-swimming performance and size of tadpoles. Similarly, increasing conspecific density increased the time to hatching of embryos and reduced the size of tadpoles, but had no effect on burst-swimming performance. The negative effect of UVBR on tadpole size was not apparent at high densities of tadpoles. This result suggests that tadpoles living at higher densities may invest relatively less energy in growth and thus have more energy to repair UVBR-induced damage. Lower densities of conspecifics increased the negative effects of UVBR on developing amphibians. Thus, low-density populations, which may include declining populations, may be particularly susceptible to the detrimental effects of increased UVBR and thus may be driven toward extinction faster than might be expected on the basis of results from single-factor studies. ©2012 Society for Conservation Biology.

Exercise and Prebiotics Produce Stress Resistance: Converging Impacts on Stress-Protective and Butyrate-Producing Gut Bacteria.

PubMed

Mika, A; Rumian, N; Loughridge, A B; Fleshner, M

2016-01-01

The gut microbial ecosystem can mediate the negative health impacts of stress on the host. Stressor-induced disruptions in microbial ecology (dysbiosis) can lead to maladaptive health effects, while certain probiotic organisms and their metabolites can protect against these negative impacts. Prebiotic diets and exercise are feasible and cost-effective strategies that can increase stress-protective bacteria and produce resistance against the detrimental behavioral and neurobiological impacts of stress. The goal of this review is to describe research demonstrating that both prebiotic diets and exercise produce adaptations in gut ecology and the brain that arm the organism against inescapable stress-induced learned helplessness. The results of this research support the novel hypothesis that some of the stress-protective effects of prebiotics and exercise are due to increases in stress-protective gut microbial species and their metabolites. In addition, new evidence also suggests that prebiotic diet or exercise interventions are most effective if given early in life (juvenile-adolescence) when both the gut microbial ecosystem and the brain are plastic. Based on our new understanding of the mechanistic convergence of these interventions, it is feasible to propose that in adults, both interventions delivered in combination may elevate their efficacy to promote a stress-resistant phenotype. © 2016 Elsevier Inc. All rights reserved.

Drought stress, plant water status, and floral trait expression in fireweed, Epilobium angustifolium (Onagraceae).

PubMed

Carroll, A B; Pallardy, S G; Galen, C

2001-03-01

In a controlled environment, we artificially induced drought during flowering of Epilobium angustifolium, an animal-pollinated plant. Leaf water potential (ψ(l)) and floral traits were monitored over a 12-d period of soil moisture depletion. Soil moisture depletion induced drought stress over time, as revealed by significant treatment × day interactions for predawn and midday ψ(l). Nectar volume and flower size showed significant negative responses to drought stress, but nectar sugar concentration did not vary between treatments. Floral traits were more buffered from drought than leaf water potentials. We used path analysis to examine direct and indirect effects of ψ(l) on floral traits for plants in well-watered (control) vs. drought treatments. According to the best-fit path models, midday ψ(l) has significant positive effects on flower size and nectar volume in both environments. However, for controls midday ψ(l) also had a significant negative effect on nectar sugar concentration. Results indicate that traits influencing floral attractiveness to pollinators in E. angustifolium vary with plant water status, such that pollinator-mediated selection could indirectly target physiological or biochemical controls on ψ(l). Moreover, under mesic conditions selection for greater nectar sugar reward may be constrained by the antagonistic effects of plant water status on nectar volume and sugar concentration.

Optimization of culturing condition and medium composition for the production of alginate lyase by a marine Vibrio sp. YKW-34

NASA Astrophysics Data System (ADS)

Fu, Xiaoting; Lin, Hong; Kim, Sang Moo

2008-02-01

Carbohydrases secreted by marine Vibrio sp. YKW-34 with strong Laminaria cell wall degrading ability were screened, and among them alginate lyase was found to be dominant. The effects of medium composition and culturing condition on the production of alginate lyase by marine Vibrio sp. YKW-34 in flask were investigated in this study. In the culture medium of marine broth, no alginate lyase was produced. The activity of the alginate lyase, after being induced, reached 5 UmL-1. The best inoculum volume and inoculum age were 10% and 12 h, respectively. The optimal temperature for alginate lyase production was 25°C. The fermentation medium was composed of 0.5% of Laminaria powder and 0.2% of KNO3 with an initial acidity of pH 8.0. Alginate could induce alginate lyase production but not as efficiently as Laminaria powder did. The addition of fucoidan, cellulose and glucose had negative effect on the alginate lyase production. Other kinds of nitrogen sources, such as yeast extract, beef extract and peptone, had positive effect on the growth of the microorganism and negative effect on alginate lyase production. In addition, the time course of alginate lyase production under the optimized condition was described. The optimal harvest time was 48 h.

Ratchet Effects, Negative Mobility, and Phase Locking for Skyrmions on Periodic Substrates

NASA Astrophysics Data System (ADS)

Reichhardt, Charles; Ray, Dipanjan; Olson Reichhardt, Cynthia

We examine the dynamics of skyrmions interacting with 1D and 2D periodic substrates in the presence of dc and ac drives. We find that the Magnus term strongly affects the skyrmion dynamics and that new kinds of phenomena can occur which are absent for overdamped ac and dc driven particles interacting with similar substrates. We show that it is possible to realize a Magnus induced ratchet for skyrmions interacting with an asymmetric potential, where the application of an ac drive can produce quantized dc motion of the skyrmions even when the ac force is perpendicular to the substrate asymmetry direction. For symmetric substrates it is also possible to achieve a negative mobility effect where the net skyrmion motion runs counter to an applied dc drive. Here, as a function of increasing dc drive, the velocity-force curves show a series of locking phases that have different features from the classic Shapiro steps found in overdamped systems. In the phase locking and ratcheting states, the skyrmions undergo intricate 2D orbits induced by the Magnus term.

DELLA proteins negatively regulate dark-induced senescence and chlorophyll degradation in Arabidopsis through interaction with the transcription factor WRKY6.

PubMed

Zhang, Yongqiang; Liu, Zhongjuan; Wang, Xiaoyun; Wang, Jianfeng; Fan, Kai; Li, Zhaowei; Lin, Wenxiong

2018-03-24

DELLA proteins' negative regulation of dark-induced senescence and chlorophyll degradation in Arabidopsis is through interaction with WRKY6 and thus repression of its transcriptional activities on senescence-related genes. Senescence is an intricate and highly orchestrated process regulated by numerous endogenous and environmental signals. Gibberellins (GAs) and their signaling components DELLA proteins have been known to participate in the regulation of senescence. However, the mechanism of the GA-DELLA system involved in the senescence process remains largely unclear. Darkness is a known environmental factor that induces plant senescence. In this study, exogenous GA 3 (an active form of GA) accelerated but paclobutrazol (a specific GA biosynthesis inhibitor) retarded dark-induced leaf yellowing in Arabidopsis. Moreover, the dark-triggered decrease in chlorophyll content, increase in cell membrane leakage, and upregulation of senescence-associated genes were notably impaired in both endogenous GA-decreased mutants ga3ox1/ga3ox2 and ga20ox1/ga20ox2 compared with those in wild-type Col-0. These effects of darkness were enhanced in the quintuple mutant of DELLA genes gai-t6/rga-t2/rgl1-1/rgl2-1/rgl3-1 and conversely attenuated in the gain-of-function mutant gai and transgenic plant 35S::TAP-RGAd17 compared with wild-type Ler. Subsequently, RGA interacted with the transcription factor WRKY6 in a yeast two-hybrid assay, as confirmed by bimolecular fluorescence complementation and pull-down analyses. In addition, mutation and overexpression of WRKY6 retarded and accelerated dark-induced senescence, respectively. Furthermore, transient expression assays in Arabidopsis protoplasts indicated that RGA and GAI weakened the transcriptional activities of WRKY6 on its downstream senescence-related genes, including SAG13 and SGR. Taken together, these results suggest that GAs positively and DELLAs negatively regulate dark-induced senescence and chlorophyll degradation in Arabidopsis. DELLAs function in this process, at least in part, by interacting with WRKY6.

Impact of psychological problems in chemical warfare survivors with severe ophthalmologic complication, a cross sectional study.

PubMed

Ghaedi, Gholamhosein; Ghasemi, Hassan; Mousavi, Batool; Soroush, Mohammad Reza; Rahnama, Parvin; Jafari, Farhad; Afshin-Majd, Siamak; Sadeghi Naeeni, Maryam; Naghizadeh, Mohammad Mehdi

2012-04-12

Sulfur mustard (SM) has been used as a chemical warfare agent since the early twentieth century. Despite the large number of studies that have investigated SM induced ocular injuries, few of those studies have also focused on the psychological health status of victims. This study has evaluated the most prominent influences on the psychological health status of patients with severe SM induced ocular injuries. This descriptive study was conducted on 149 Iranian war veterans with severe SM induced eye injuries. The psychological health status of all patients was assessed using the Iranian standardized Symptom Check List 90-Revised (SCL90-R) questionnaire. The results of patients' Global Severity Index (GSI) were compared with the optimal cut-off point of 0.4 that has previously been calculated for GSI in Iranian community. The Mann-Whitney U test, T tests and effect sizes (using Cohen's d) were employed as statistical methods. Data were analyzed using SPSS software. The mean age of patients was 44.86 (SD=8.7) and mean duration of disease was 21.58 (SD=1.20) years. Rate of exposure was once in 99 (66.4%) cases. The mean GSI (1.46) of the study group was higher compared to standardized cut off point (0.4) of the Iranian community. The results of this study showed that the mean of total GSI score was higher in participants with lower educational levels (effect size=0.507), unemployment (effect size=0.464) and having more than 3 children (effect size=0.62). Among the participants, 87 (58.4%) cases had a positive psychological history for hospitalization or receiving outpatient cares previously and 62 (41.6%) cases had a negative psychological history. In addition, the mean of GSI in participants with negative psychological history was lower than those with positive psychological history (Mean Change Difference=-0.621 with SD=0.120). There was a significant difference between positive and negative psychological history with respect to GSI (P<0.001). The study showed that severe ophthalmologic complications in chemical survivors are accompanied with destructive effects on psychological health status. Appropriate management may improve psychological health status in these patients.

Selective decontamination of the digestive tract ameliorates severe burn-induced insulin resistance in rats.

PubMed

Li, Jun; Zhu, Liang; Xu, Ming; Han, Juntao; Bai, Xiaozhi; Yang, Xuekang; Zhu, Huayu; Xu, Jie; Zhang, Xing; Gong, Yangfan; Hu, Dahai; Gao, Feng

2015-08-01

Severe burns often initiate the prevalence of hyperglycemia and insulin resistance, significantly contributing to adverse clinical outcomes. However, there are limited treatment options. This study was designed to investigate the role and the underlying mechanisms of oral antibiotics to selectively decontaminate the digestive tract (SDD) on burn-induced insulin resistance. Rats were subjected to 40% of total body surface area full-thickness burn or sham operation with or without SDD treatment. Translocation of FITC-labeled LPS was measured at 4h after burn. Furthermore, the effect of SDD on post-burn quantity of gram-negative bacteria in gut was investigated. Serum or muscle LPS and proinflammatory cytokines were measured. Intraperitoneal glucose tolerance test and insulin tolerance test were used to determine the status of systemic insulin resistance. Furthermore, intracellular insulin signaling (IRS-1 and Akt) and proinflammatory related kinases (JNK and IKKβ) were assessed by western blot. Burn increased the translocation of LPS from gut 4h after injury. SDD treatment effectively inhibited post-burn overgrowth of gram-negative enteric bacilli in gut. In addition, severe burns caused significant increases in the LPS and proinflammatory cytokines levels, activation of proinflammatory related kinases, and systemic insulin resistance as well. But SDD treatment could significantly attenuate burn-induced insulin resistance and improve the whole-body responsiveness to insulin, which was associated with the inhibition of gut-derived LPS, cytokines, proinflammatory related kinases JNK and IKKβ, as well as activation of IRS-1 and Akt. SDD appeared to have an effect on proinflammatory signaling cascades and further reduced severe burn-induced insulin resistance. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Ethanol-induced locomotor activity in adolescent rats and the relationship with ethanol-induced conditioned place preference and conditioned taste aversion.

PubMed

Acevedo, María Belén; Nizhnikov, Michael E; Spear, Norman E; Molina, Juan C; Pautassi, Ricardo M

2013-05-01

Adolescent rats exhibit ethanol-induced locomotor activity (LMA), which is considered an index of ethanol's motivational properties likely to predict ethanol self-administration, but few studies have reported or correlated ethanol-induced LMA with conditioned place preference (CPP) by ethanol at this age. The present study assessed age-related differences in ethanol's motor stimulating effects and analyzed the association between ethanol-induced LMA and conventional measures of ethanol-induced reinforcement. Experiment 1 compared ethanol-induced LMA in adolescent and adult rats. Subsequent experiments analyzed ethanol-induced CPP and conditioned taste aversion (CTA) in adolescent rats evaluated for ethanol-induced LMA. Adolescent rats exhibit a robust LMA after high-dose ethanol. Ethanol-induced LMA was fairly similar across adolescents and adults. As expected, adolescents were sensitive to ethanol's aversive reinforcement, but they also exhibited CPP. These measures of ethanol reinforcement, however, were not related to ethanol-induced LMA. Spontaneous LMA in an open field was, however, negatively associated with ethanol-induced CTA. Copyright © 2012 Wiley Periodicals, Inc.

ETHANOL-INDUCED LOCOMOTOR ACTIVITY IN ADOLESCENT RATS AND THE RELATIONSHIP WITH ETHANOL-INDUCED CONDITIONED PLACE PREFERENCE AND CONDITIONED TASTE AVERSION

PubMed Central

Acevedo, María Belén; Nizhnikov, Michael E.; Spear, Norman E.; Molina, Juan C.; Pautassi, Ricardo Marcos

2012-01-01

Adolescent rats exhibit ethanol-induced locomotor activity (LMA), which is considered an index of ethanol’s motivational properties likely to predict ethanol self-administration, but few studies have reported or correlated ethanol-induced LMA with conditioned place preference by ethanol at this age. The present study assessed age-related differences in ethanol’s motor stimulating effects and analysed the association between ethanol-induced LMA and conventional measures of ethanol-induced reinforcement. Experiment 1 compared ethanol-induced LMA in adolescent and adult rats. Subsequent experiments analyzed ethanol-induced conditioned place preference and conditioned taste aversion in adolescent rats evaluated for ethanol-induced LMA. Adolescent rats exhibit a robust LMA after high-dose ethanol. Ethanol-induced LMA was fairly similar across adolescents and adults. As expected, adolescents were sensitive to ethanol’s aversive reinforcement, but they also exhibited conditioned place preference. These measures of ethanol reinforcement, however, were not related to ethanol-induced LMA. Spontaneous LMA in an open field was, however, negatively associated with ethanol-induced CTA. PMID:22592597

Field-effect Flow Control in Polymer Microchannel Networks

NASA Technical Reports Server (NTRS)

Sniadecki, Nathan; Lee, Cheng S.; Beamesderfer, Mike; DeVoe, Don L.

2003-01-01

A new Bio-MEMS electroosmotic flow (EOF) modulator for plastic microchannel networks has been developed. The EOF modulator uses field-effect flow control (FEFC) to adjust the zeta potential at the Parylene C microchannel wall. By setting a differential EOF pumping rate in two of the three microchannels at a T-intersection with EOF modulators, the induced pressure at the intersection generated pumping in the third, field-free microchannel. The EOF modulators are able to change the magnitude and direction of the pressure pumping by inducing either a negative or positive pressure at the intersection. The flow velocity is tracked by neutralized fluorescent microbeads in the microchannels. The proof-of-concept of the EOF modulator described here may be applied to complex plastic ,microchannel networks where individual microchannel flow rates are addressable by localized induced-pressure pumping.

Effects of natural and chemically synthesized furanones on quorum sensing in Chromobacterium violaceum

PubMed Central

Martinelli, Daniel; Grossmann, Gilles; Séquin, Urs; Brandl, Helmut; Bachofen, Reinhard

2004-01-01

Background Cell to cell signaling systems in Gram-negative bacteria rely on small diffusible molecules such as the N-acylhomoserine lactones (AHL). These compounds are involved in the production of antibiotics, exoenzymes, virulence factors and biofilm formation. They belong to the class of furanone derivatives which are frequently found in nature as pheromones, flavor compounds or secondary metabolites. To obtain more information on the relation between molecular structure and quorum sensing, we tested a variety of natural and chemically synthesized furanones for their ability to interfere with the quorum sensing mechanism using a quantitative bioassay with Chromobacterium violaceum CV026 for antagonistic and agonistic action. We were looking at the following questions: 1. Do these compounds affect growth? 2) Do these compounds activate the quorum sensing system of C. violaceum CV026? 3) Do these compounds inhibit violacein formation induced by the addition of the natural inducer N-hexanoylhomoserine lactone (HHL)? 4) Do these compounds enhance violacein formation in presence of HHL? Results The naturally produced N-acylhomoserine lactones showed a strong non-linear concentration dependent influence on violacein production in C. violaceum with a maximum at 3.7*10-8 M with HHL. Apart from the N-acylhomoserine lactones only one furanone (emoxyfurane) was found to simulate N-acylhomoserine lactone activity and induce violacein formation. The most effective substances acting negatively both on growth and quorum sensing were analogs and intermediates in synthesis of the butenolides from Streptomyces antibioticus. Conclusion As the regulation of many bacterial processes is governed by quorum sensing systems, the finding of natural and synthetic furanones acting as agonists or antagonists suggests an interesting tool to control and handle detrimental AHL induced effects. Some effects are due to general toxicity; others are explained by a competitive interaction for LuxR proteins. For further experiments it is important to be aware of the fact that quorum sensing active compounds have non-linear effects. Inducers can act as inhibitors and inhibitors might be able to activate or enhance the quorum sensing system depending on chemical structure and concentration levels. PMID:15233843

Soliton-induced relativistic-scattering and amplification.

PubMed

Rubino, E; Lotti, A; Belgiorno, F; Cacciatori, S L; Couairon, A; Leonhardt, U; Faccio, D

2012-01-01

Solitons are of fundamental importance in photonics due to applications in optical data transmission and also as a tool for investigating novel phenomena ranging from light generation at new frequencies and wave-trapping to rogue waves. Solitons are also moving scatterers: they generate refractive index perturbations moving at the speed of light. Here we found that such perturbations scatter light in an unusual way: they amplify light by the mixing of positive and negative frequencies, as we describe using a first Born approximation and numerical simulations. The simplest scenario in which these effects may be observed is within the initial stages of optical soliton propagation: a steep shock front develops that may efficiently scatter a second, weaker probe pulse into relatively intense positive and negative frequency modes with amplification at the expense of the soliton. Our results show a novel all-optical amplification scheme that relies on soliton induced scattering.

Negative inotropic effect of carbachol and interaction between acetylcholine receptor-operated potassium channel (K.ACh channel) and GTP binding protein in mouse isolated atrium--a novel methodological trial.

PubMed

Okada, Muneyoshi; Noma, Chihiro; Yamawaki, Hideyuki; Hara, Yukio

2013-01-01

Interaction between acetylcholine receptor-operated potassium channel (K.ACh channel) and GTP binding protein was examined by an immunoprecipitation-Western blotting system in mouse isolated atrium. The carbachol-induced negative inotropic action in indomethacin-pretreated mouse atrium was significantly inhibited by a K.ACh channel blocker, tertiapin or atropine. Kir3.1 K.ACh channel (Kir3.1) was immunoprecipitated with a mouse anti-Kir3.1 antibody. Coprecipitating Gβ with Kir3.1, detected by Western blotting, was significantly augmented by carbachol. Atropine, but not tertiapin, significantly inhibited the carbachol-induced coprecipitating Gβ with Kir3.1. The data indicate that immunoprecipitation with Kir3.1 and Western blotting of Gβ system is a useful method for assessing interaction between K.ACh channel and GTP binding protein in mouse atrium.

Galactose-1-phosphate uridyltransferase (GalT), an in vivo-induced antigen of Actinobacillus pleuropneumoniae serovar 5b strain L20, provided immunoprotection against serovar 1 strain MS71.

PubMed

Zhang, Fei; Zhao, Qin; Quan, Keji; Zhu, Zhuang; Yang, Yusheng; Wen, Xintian; Chang, Yung-Fu; Huang, Xiaobo; Wu, Rui; Wen, Yiping; Yan, Qigui; Huang, Yong; Ma, Xiaoping; Han, Xinfeng; Cao, Sanjie

2018-01-01

GALT is an important antigen of Actinobacillus pleuropneumoniae (APP), which was shown to provide partial protection against APP infection in a previous study in our lab. The main purpose of the present study is to investigate GALT induced cross-protection between different APP serotypes and elucidate key mechanisms of the immune response to GALT antigenic stimulation. Bioinformatic analysis demonstrated that galT is a highly conserved gene in APP, widely distributed across multiple pathogenic strains. Homologies between any two strains ranges from 78.9% to 100% regarding the galT locus. Indirect enzyme-linked immunosorbent assay (ELISA) confirmed that GALT specific antibodies could not be induced by inactivated APP L20 or MS71 whole cell bacterin preparations. A recombinant fusion GALT protein derived from APP L20, however has proven to be an effective cross-protective antigen against APP sevorar 1 MS71 (50%, 4/8) and APP sevorar 5b L20 (75%, 6/8). Histopathological examinations have confirmed that recombinant GALT vaccinated animals showed less severe pathological signs in lung tissues than negative controls after APP challenge. Immunohistochemical (IHC) analysis indicated that the infiltration of neutrophils in the negative group is significantly increased compared with that in the normal control (P<0.001) and that in surviving animals is decreased compared to the negative group. Anti-GALT antibodies were shown to mediate phagocytosis of neutrophils. After interaction with anti-GALT antibodies, survival rate of APP challenged vaccinated animals was significantly reduced (P<0.001). This study demonstrated that GALT is an effective cross-protective antigen, which could be used as a potential vaccine candidate against multiple APP serotypes.

Curcumin Induces Apoptosis of Upper Aerodigestive Tract Cancer Cells by Targeting Multiple Pathways

PubMed Central

Amin, A. R. M. Ruhul; Haque, Abedul; Rahman, Mohammad Aminur; Chen, Zhuo Georgia; Khuri, Fadlo Raja; Shin, Dong Moon

2015-01-01

Curcumin, a natural compound isolated from the Indian spice "Haldi" or "curry powder", has been used for centuries as a traditional remedy for many ailments. Recently, the potential use of curcumin in cancer prevention and therapy urges studies to uncover the molecular mechanisms associated with its anti-tumor effects. In the current manuscript, we investigated the mechanism of curcumin-induced apoptosis in upper aerodigestive tract cancer cell lines and showed that curcumin-induced apoptosis is mediated by the modulation of multiple pathways such as induction of p73, and inhibition of p-AKT and Bcl-2. Treatment of cells with curcumin induced both p53 and the related protein p73 in head and neck and lung cancer cell lines. Inactivation of p73 by dominant negative p73 significantly protected cells from curcumin-induced apoptosis, whereas ablation of p53 by shRNA had no effect. Curcumin treatment also strongly inhibited p-AKT and Bcl-2 and overexpression of constitutively active AKT or Bcl-2 significantly inhibited curcumin-induced apoptosis. Taken together, our findings suggest that curcumin-induced apoptosis is mediated via activating tumor suppressor p73 and inhibiting p-AKT and Bcl-2. PMID:25910231

Myricetin-induced apoptosis of triple-negative breast cancer cells is mediated by the iron-dependent generation of reactive oxygen species from hydrogen peroxide.

PubMed

Knickle, Allison; Fernando, Wasundara; Greenshields, Anna L; Rupasinghe, H P Vasantha; Hoskin, David W

2018-05-06

Myricetin is a dietary phytochemical with anticancer activity; however, the effect of myricetin on breast cancer cells remains unclear. Here, we show that myricetin inhibited the growth of triple-negative breast cancer (TNBC) cells but was less inhibitory for normal cells. The effect of myricetin was comparable to epigallocatechin gallate and doxorubicin, and greater than resveratrol and cisplatin. Myricetin-treated TNBC cells showed evidence of early and late apoptosis/necrosis, which was associated with intracellular reactive oxygen species (ROS) accumulation, extracellular regulated kinase 1/2 and p38 mitogen-activated protein kinase activation, mitochondrial membrane destabilization and cytochrome c release, and double-strand DNA breaks. The antioxidant N-acetyl-cysteine protected myricetin-treated TNBC cells from cytotoxicity due to DNA damage. Myricetin also induced hydrogen peroxide (H 2 O 2 ) production in cell-free culture medium, as well as in the presence of TNBC cells and normal cells. In addition, deferriprone-mediated inhibition of intracellular ROS generation via the iron-dependent Fenton reaction and inhibition of extracellular ROS accumulation with superoxide dismutase plus catalase prevented myricetin-induced cytotoxicity in TNBC cell cultures. We conclude that the cytotoxic effect of myricetin on TNBC cells was due to oxidative stress initiated by extracellular H 2 O 2 formed by autoxidation of myricetin, leading to intracellular ROS production via the Fenton reaction. Copyright © 2018. Published by Elsevier Ltd.

Fluctuations, ghosts, and the cosmological constant

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

Hirayama, T.; Holdom, B.

2004-12-15

For a large region of parameter space involving the cosmological constant and mass parameters, we discuss fluctuating spacetime solutions that are effectively Minkowskian on large time and distance scales. Rapid, small amplitude oscillations in the scale factor have a frequency determined by the size of a negative cosmological constant. A field with modes of negative energy is required. If it is gravity that induces a coupling between the ghostlike and normal fields, we find that this results in stochastic rather than unstable behavior. The negative energy modes may also permit the existence of Lorentz invariant fluctuating solutions of finite energymore » density. Finally we consider higher derivative gravity theories and find oscillating metric solutions in these theories without the addition of other fields.« less

Impact of present and past antipsychotic side effects on attitude toward typical antipsychotic treatment and adherence.

PubMed

Lambert, M; Conus, P; Eide, P; Mass, R; Karow, A; Moritz, S; Golks, D; Naber, D

2004-11-01

(1) determine which antipsychotic side effects (SE) schizophrenic patients consider the most distressing during treatment with typical antipsychotics, (2) measure the impact of actual and past SE on patients' attitude toward antipsychotics and (3) assess the influence of both on adherence. The 213 schizophrenics, treated with conventional antipsychotics, were recruited in two psychiatric hospitals in Hamburg. Subjects were assessed about type and severity of present and past side effects and their attitude and adherence to antipsychotic treatment. The 82 (39%) patients presented present SE while 131 (61%) did not. Sexual dysfunctions (P < 0.001), extrapyramidal (P < 0.05) and psychic side effects (P < 0.05) were rated as significantly subjectively more distressing than sedation or vegetative side effects. Patients presenting with present SE compared with patients without present SE had a significantly more negative general attitude toward antipsychotics (P < 0.05), were more doubtful about their efficacy (P < 0.01) and were less likely to encourage a relative to take such a medication in case of need (P < 0.001). A regression analysis indicated that nonadherence was mainly influenced by negative general and efficacy attitudes toward antipsychotics and the experience of past or present antipsychotic side effects. All antipsychotic side effects, present or past, can have a durable negative impact on patient's attitude toward antipsychotic treatment and adherence. Non-adherence is mainly determined, among other factors, by these negative attitudes, which are partly influenced by the experience of past or present antipsychotic-induced side effects.

Effect of Negative Pressure on Proliferation, Virulence Factor Secretion, Biofilm Formation, and Virulence-Regulated Gene Expression of Pseudomonas aeruginosa In Vitro

PubMed Central

Wang, Guo-Qi; Li, Tong-Tong; Li, Zhi-Rui; Zhang, Li-Cheng

2016-01-01

Objective. To investigate the effect of negative pressure conditions induced by NPWT on P. aeruginosa. Methods. P. aeruginosa was cultured in a Luria–Bertani medium at negative pressure of −125 mmHg for 24 h in the experimental group and at atmospheric pressure in the control group. The diameters of the colonies of P. aeruginosa were measured after 24 h. ELISA kit, orcinol method, and elastin-Congo red assay were used to quantify the virulence factors. Biofilm formation was observed by staining with Alexa Fluor® 647 conjugate of concanavalin A (Con A). Virulence-regulated genes were determined by quantitative RT-PCR. Results. As compared with the control group, growth of P. aeruginosa was inhibited by negative pressure. The colony size under negative pressure was significantly smaller in the experimental group than that in the controls (p < 0.01). Besides, reductions in the total amount of virulence factors were observed in the negative pressure group, including exotoxin A, rhamnolipid, and elastase. RT-PCR results revealed a significant inhibition in the expression level of virulence-regulated genes. Conclusion. Negative pressure could significantly inhibit the growth of P. aeruginosa. It led to a decrease in the virulence factor secretion, biofilm formation, and a reduction in the expression level of virulence-regulated genes. PMID:28074188

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

PubMed

Köhr, G; Heinemann, U

1988-01-01

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

F15063, a compound with D2/D3 antagonist, 5-HT1A agonist and D4 partial agonist properties: (III) Activity in models of cognition and negative symptoms

PubMed Central

Depoortère, R; Auclair, A L; Bardin, L; Slot, L Bruins; Kleven, M S; Colpaert, F; Vacher, B; Newman-Tancredi, A

2007-01-01

Background and purpose: The D2/D3 receptor antagonist, D4 receptor partial agonist, and high efficacy 5-HT1A receptor agonist F15063 was shown to be highly efficacious and potent in rodent models of activity against positive symptoms of schizophrenia. However F15063 induced neither catalepsy nor the ‘serotonin syndrome'. Here, we evaluated its profile in rat models predictive of efficacy against negative symptoms/cognitive deficits of schizophrenia. Experimental approach: F15063, given i.p., was assessed in models of behavioural deficits induced by interference with the NMDA/glutamatergic (phencyclidine: PCP) or cholinergic (scopolamine) systems. Key results: Through 5-HT1A activation, F15063 partially alleviated (MED: 0.04 mg kg−1) PCP-induced social interaction deficit between two adult rats, without effect by itself, underlining its potential to combat negative symptoms. At doses above 0.16 mg kg−1, F15063 reduced interaction by itself. F15063 (0.16 mg kg−1) selectively re-established PCP-impaired ‘cognitive flexibility' in a reversal learning task, suggesting potential against adaptability deficits. F15063 (0.04–0.63 mg kg−1) also reversed scopolamine-induced amnesia in a juvenile-adult rat social recognition test, indicative of a pro-cholinergic influence. Activity in this latter test is consistent with its D4 partial agonism, as it was blocked by the D4 antagonist L745,870. Finally, F15063 up to 40 mg kg−1 did not disrupt basal prepulse inhibition of startle reflex in rats, a marker of sensorimotor gating. Conclusions and implications: The balance of D2/D3, D4 and 5-HT1A receptor interactions of F15063 yields a promising profile of activity in models of cognitive deficits and negative symptoms of schizophrenia. PMID:17375085

Brassinosteroid-Induced Transcriptional Repression and Dephosphorylation-Dependent Protein Degradation Negatively Regulate BIN2-Interacting AIF2 (a BR Signaling-Negative Regulator) bHLH Transcription Factor.

PubMed

Kim, Yoon; Song, Ji-Hye; Park, Seon-U; Jeong, You-Seung; Kim, Soo-Hwan

2017-02-01

Brassinosteroids (BRs) are plant polyhydroxy-steroids that play important roles in plant growth and development via extensive signal integration through direct interactions between regulatory components of different signaling pathways. Recent studies have shown that diverse helix-loop-helix/basic helix-loop-helix (HLH/bHLH) family proteins are actively involved in control of BR signaling pathways and interact with other signaling pathways. In this study, we show that ATBS1-INTERACTING FACTOR 2 (AIF2), a nuclear-localized atypical bHLH transcription factor, specifically interacts with BRASSINOSTEROID-INSENSITIVE 2 (BIN2) among other BR signaling molecules. Overexpression of AIF2 down-regulated transcript expression of growth-promoting genes, thus resulting in retardation of growth. AIF2 renders plants hyposensitive to BR-induced root growth inhibition, but shows little effects on BR-promoted hypocotyl elongation. Notably, AIF2 was dephosphorylated by BR, and the dephosphorylated AIF2 was subject to proteasome-mediated degradation. AIF2 degradation was greatly induced by BR and ABA, but relatively slightly by other hormones such as auxin, gibberellin, cytokinin and ethylene. Moreover, AIF2 transcription was significantly suppressed by a BRI1/BZR1-mediated BR signaling pathway through a direct binding of BRASSINAZOLE RESISTANT 1 (BZR1) to the BR response element (BRRE) region of the AIF2 promoter. In conclusion, our study suggests that BIN2-driven AIF2 phosphorylation could augment the BIN2/AIF2-mediated negative circuit of BR signaling pathways, and the BR-induced transcriptional repression and protein degradation negatively regulate AIF2 transcription factor, reinforcing the BZR1/BES1-mediated positive BR signaling pathway. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Lapatinib increases motility of triple-negative breast cancer cells by decreasing miRNA-7 and inducing Raf-1/MAPK-dependent interleukin-6.

PubMed

Hsiao, Yu-Chun; Yeh, Ming-Hsin; Chen, Yun-Ju; Liu, Ju-Fang; Tang, Chih-Hsin; Huang, Wei-Chien

2015-11-10

Lapatinib, a dual epidermal growth factor receptor (EGFR) and HER2 tyrosine kinase inhibitor (TKI), has been approved for HER2-positive breast cancer patients. Nevertheless, its inhibitory effect on EGFR did not deliver clinical benefits for triple-negative breast cancer (TNBC) patients even EGFR overexpression was frequently found in this disease. Moreover, lapatinib was unexpectedly found to enhance metastasis of TNBC cells, but the underlying mechanisms are not fully understood. In this study, we explored that the level of interleukin-6 (IL-6) was elevated in lapatinib-treated TNBC cells. Treatment with IL-6 antibody abolished the lapatinib-induced migration. Mechanistically, the signaling axis of Raf-1/mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinases (JNKs), p38 MAPK, and activator protein 1 (AP-1) was activated in response to lapatinib treatment to induce IL-6 expression. Furthermore, our data showed that microRNA-7 directly binds and inhibits Raf-1 3'UTR activity, and that down-regulation of miR-7 by lapatinib contributes to the activation of Raf-1 signaling pathway and the induction of IL-6 expression. Our results not only revealed IL-6 as a key regulator of lapatinib-induced metastasis, but also explored the requirement of miR7/Raf-1/MAPK/AP-1 axis in lapatinib-induced IL-6 expression.

Lapatinib increases motility of triple-negative breast cancer cells by decreasing miRNA-7 and inducing Raf-1/MAPK-dependent interleukin-6

PubMed Central

Chen, Yun-Ju; Liu, Ju-Fang; Tang, Chih-Hsin; Huang, Wei-Chien

2015-01-01

Lapatinib, a dual epidermal growth factor receptor (EGFR) and HER2 tyrosine kinase inhibitor (TKI), has been approved for HER2-positive breast cancer patients. Nevertheless, its inhibitory effect on EGFR did not deliver clinical benefits for triple-negative breast cancer (TNBC) patients even EGFR overexpression was frequently found in this disease. Moreover, lapatinib was unexpectedly found to enhance metastasis of TNBC cells, but the underlying mechanisms are not fully understood. In this study, we explored that the level of interleukin-6 (IL-6) was elevated in lapatinib-treated TNBC cells. Treatment with IL-6 antibody abolished the lapatinib-induced migration. Mechanistically, the signaling axis of Raf-1/mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinases (JNKs), p38 MAPK, and activator protein 1 (AP-1) was activated in response to lapatinib treatment to induce IL-6 expression. Furthermore, our data showed that microRNA-7 directly binds and inhibits Raf-1 3′UTR activity, and that down-regulation of miR-7 by lapatinib contributes to the activation of Raf-1 signaling pathway and the induction of IL-6 expression. Our results not only revealed IL-6 as a key regulator of lapatinib-induced metastasis, but also explored the requirement of miR7/Raf-1/MAPK/AP-1 axis in lapatinib-induced IL-6 expression. PMID:26513016

Electroencephalography Based Analysis of Working Memory Load and Affective Valence in an N-back Task with Emotional Stimuli

PubMed Central

Grissmann, Sebastian; Faller, Josef; Scharinger, Christian; Spüler, Martin; Gerjets, Peter

2017-01-01

Most brain-based measures of the electroencephalogram (EEG) are used in highly controlled lab environments and only focus on narrow mental states (e.g., working memory load). However, we assume that outside the lab complex multidimensional mental states are evoked. This could potentially create interference between EEG signatures used for identification of specific mental states. In this study, we aimed to investigate more realistic conditions and therefore induced a combination of working memory load and affective valence to reveal potential interferences in EEG measures. To induce changes in working memory load and affective valence, we used a paradigm which combines an N-back task (for working memory load manipulation) with a standard method to induce affect (affective pictures taken from the International Affective Picture System (IAPS) database). Subjective ratings showed that the experimental task was successful in inducing working memory load as well as affective valence. Additionally, performance measures were analyzed and it was found that behavioral performance decreased with increasing workload as well as negative valence, showing that affective valence can have an effect on cognitive processing. These findings are supported by changes in frontal theta and parietal alpha power, parameters used for measuring of working memory load in the EEG. However, these EEG measures are influenced by the negative valence condition as well and thereby show that detection of working memory load is sensitive to affective contexts. Unexpectedly, we did not find any effects for EEG measures typically used for affective valence detection (Frontal Alpha Asymmetry (FAA)). Therefore we assume that the FAA measure might not be usable if cognitive workload is induced simultaneously. We conclude that future studies should account for potential context-specifity of EEG measures. PMID:29311875

Fight or flight? - Flight increases immune gene expression but does not help to fight an infection.

PubMed

Woestmann, L; Kvist, J; Saastamoinen, M

2017-03-01

Flight represents a key trait in most insects, being energetically extremely demanding, yet often necessary for foraging and reproduction. Additionally, dispersal via flight is especially important for species living in fragmented landscapes. Even though, based on life-history theory, a negative relationship may be expected between flight and immunity, a number of previous studies have indicated flight to induce an increased immune response. In this study, we assessed whether induced immunity (i.e. immune gene expression) in response to 15-min forced flight treatment impacts individual survival of bacterial infection in the Glanville fritillary butterfly (Melitaea cinxia). We were able to confirm previous findings of flight-induced immune gene expression, but still observed substantially stronger effects on both gene expression levels and life span due to bacterial infection compared to flight treatment. Even though gene expression levels of some immunity-related genes were elevated due to flight, these individuals did not show increased survival of bacterial infection, indicating that flight-induced immune activation does not completely protect them from the negative effects of bacterial infection. Finally, an interaction between flight and immune treatment indicated a potential trade-off: flight treatment increased immune gene expression in naïve individuals only, whereas in infected individuals no increase in immune gene expression was induced by flight. Our results suggest that the up-regulation of immune genes upon flight is based on a general stress response rather than reflecting an adaptive response to cope with potential infections during flight or in new habitats. © 2016 The Authors. Journal of Evolutionary Biology Published by John Wiley & Sons ltd on behalf of European Society for Evolutionary Biology.

Ellagic and ferulic acids alleviate gamma radiation and aluminium chloride-induced oxidative damage.

PubMed

Salem, Ahmed M; Mohammaden, Tarek F; Ali, Mohamed A M; Mohamed, Enas A; Hasan, Hesham F

2016-09-01

Ionizing radiation interacts with biological systems through the generation of free radicals, which induce oxidative stress. Aluminium (Al) can negatively impact human health by direct interaction with antioxidant enzymes. Ellagic acid (EA) and Ferulic acid (FA) are plant polyphenolic compounds, have gained attention due to their multiple biological activities. To date, no studies investigating the antioxidant effect of EA/FA in a model involving both γ radiation and aluminium chloride (AlCl3) have been reported. Herein, we investigated the protective effect of EA and FA against oxidative stress induced by γ radiation and AlCl3 in rats. Rats were divided into thirteen groups: a negative control group, 3 positive control groups (γ-irradiated, AlCl3-treated and γ-irradiated+AlCl3-treated) and 9 groups (3 γ-irradiated, 3 AlCl3-treated and 3 γ-irradiated+AlCl3-treated) treated with EA and/or FA. Liver function and lipid profile were assessed. Levels of lipid peroxidation, protein oxidation and endogenous antioxidants as well as the concentrations of copper, iron and zinc were estimated in liver tissue homogenate. Furthermore, liver tissue sections were histologically examined. Oral administration of EA and/or FA resulted in 1) amelioration of AlCl3 and/or γ-radiation-induced hepatic function impairment, dyslipidemia and hepatic histological alterations; 2) reduction in liver MDA and PCC levels; 3) elevation of liver CAT, GPx and SOD activity as well as GSH level; 4) elevation in liver Cu concentrations which was accompanied by a reduction in Fe and Zn concentrations. Oral administration of EA and/or FA may be useful for ameliorating γ radiation and/or AlCl3-induced oxidative damage. Copyright © 2016 Elsevier Inc. All rights reserved.

Electroencephalography Based Analysis of Working Memory Load and Affective Valence in an N-back Task with Emotional Stimuli.

PubMed

Grissmann, Sebastian; Faller, Josef; Scharinger, Christian; Spüler, Martin; Gerjets, Peter

2017-01-01

Most brain-based measures of the electroencephalogram (EEG) are used in highly controlled lab environments and only focus on narrow mental states (e.g., working memory load). However, we assume that outside the lab complex multidimensional mental states are evoked. This could potentially create interference between EEG signatures used for identification of specific mental states. In this study, we aimed to investigate more realistic conditions and therefore induced a combination of working memory load and affective valence to reveal potential interferences in EEG measures. To induce changes in working memory load and affective valence, we used a paradigm which combines an N-back task (for working memory load manipulation) with a standard method to induce affect (affective pictures taken from the International Affective Picture System (IAPS) database). Subjective ratings showed that the experimental task was successful in inducing working memory load as well as affective valence. Additionally, performance measures were analyzed and it was found that behavioral performance decreased with increasing workload as well as negative valence, showing that affective valence can have an effect on cognitive processing. These findings are supported by changes in frontal theta and parietal alpha power, parameters used for measuring of working memory load in the EEG. However, these EEG measures are influenced by the negative valence condition as well and thereby show that detection of working memory load is sensitive to affective contexts. Unexpectedly, we did not find any effects for EEG measures typically used for affective valence detection (Frontal Alpha Asymmetry (FAA)). Therefore we assume that the FAA measure might not be usable if cognitive workload is induced simultaneously. We conclude that future studies should account for potential context-specifity of EEG measures.

The dopamine antagonist cis-flupenthixol blocks the expression of the conditioned positive but not the negative effects of cocaine in rats

PubMed Central

Wenzel, Jennifer M.; Su, Zu-In; Shelton, Kerisa; Dominguez, Hiram M.; von Furstenberg, Victoria A.; Ettenberg, Aaron

2013-01-01

Human cocaine users report that the initial “high” produced by cocaine administration is followed by an anxiogenic “crash”. Given that cocaine has such robust and opposing properties, it is likely that both the positive and negative effects of cocaine contribute to an individual’s motivation to administer the drug. Despite this likelihood, the neurobiology underlying cocaine’s dual processes remains unclear. While much literature supports a role for dopamine (DA) in cocaine reward, it is uncertain if DA also contributes to the drug’s negative effects. Our laboratory has extensively utilized a modified conditioned place test to explore cocaine’s opponent processes. In this paradigm rats develop conditioned place preferences (CPPs) for an environment paired with the immediate/positive effects of cocaine, and conditioned place aversions (CPAs) for an environment paired with the delayed/negative effects present 15-min after i.v. injection. In the current study rats were conditioned to associate an environment with either the immediate or delayed effects of i.v. cocaine (1 mg/kg/0.1 ml) three hours after i.p. pre-treatment with either the DA D1/D2 receptor antagonist cis-flupenthixol (0.5 mg/kg/ml) or saline vehicle. As expected, vehicle-treated control animals developed the normal pattern of CPPs for cocaine’s immediate effects or CPAs for the delayed effects of cocaine. However, while DA receptor antagonism prevented the expression of cocaine CPPs it did not alter the expression of cocaine-induced CPAs. These data confirm a role for DA transmission in cocaine reward but suggest that different neural pathways mediate the drug’s negative/anxiogenic properties. PMID:24012795

Protective effect of grape seed and skin extract against diabetes-induced oxidative stress and renal dysfunction in virgin and pregnant rat.

PubMed

Oueslati, Nourhene; Charradi, Kamel; Bedhiafi, Takwa; Limam, Ferid; Aouani, Ezzedine

2016-10-01

The present work deal with the effect of alloxan-induced diabetes on kidney oxidative stress and dysfunction of virgin and pregnant rat as well as the protection that may be afforded by high dosage GSSE (4g/kg) treatment. Diabetes affected negatively several kidney function parameters as creatinemia, uremia, uricemia and proteinuria without affecting kidney index. Diabetes also induced an oxidative stress characterized by increased lipid and protein oxidation, a drop in antioxidant enzyme defenses as catalase, superoxide-dismutase, glutathione-peroxidase, an alteration in transition metals as free iron, copper, selenium and associated enzymes and an increase in calpain and acetyl-cholinesterase activities. Tremendously, GSSE treatment protected efficiently against all the deleterious effects of diabetes-induced kidney dysfunction in both virgin and pregnant animals. High dosage GSSE is a safe and potent anti-oxidant that may be further tested in clinical trials for the long-term preservation of kidney function especially in multiple pregnancies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Serotonergic psychedelics and personality: A systematic review of contemporary research.

PubMed

Bouso, José Carlos; Dos Santos, Rafael G; Alcázar-Córcoles, Miguel Ángel; Hallak, Jaime E C

2018-04-01

Serotonergic psychedelics act as agonists at cortical 5-HT 2A receptors and seem to induce personality changes. We conducted a systematic review of studies assessing the effects of these drugs on personality. Papers published from 1985-2016 were included from PubMed, LILACS, and SciELO databases. Three hundred and sixty-nine studies were identified, and 18 were included. Specific personality traits, such as Absorption and Self-Transcendence, seem to influence the effects of psychedelics, and psychedelic drug users and nonusers appear to differ in some personality traits. Psychedelics administered in controlled settings may induce personality changes, such as increased Openness and Self-Transcendence. Increases in global brain entropy induced by acute psychedelic administration predicted changes in Openness, and Self-Transcendence was negatively correlated with cortical thinning of the posterior cingulate cortex in long-term religious ayahuasca users. Acute and long-term use of psychedelics is associated with personality changes that appear to be modulated by 5-HT 2A receptors. These changes seem to induce therapeutic effects that should be further explored in randomized controlled studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adverse Health Effects of Thirdhand Smoke: From Cell to Animal Models.

PubMed

Hang, Bo; Wang, Pin; Zhao, Yue; Sarker, Altaf; Chenna, Ahmed; Xia, Yankai; Snijders, Antoine M; Mao, Jian-Hua

2017-04-28

The newly identified smoke hazard, thirdhand smoke (THS), has gained public attention in recent years but its health impact and biological effects are largely unknown. THS may be defined by "the four Rs": tobacco chemicals that remain, react, re-emit, and/or are resuspended long after active smoking has ceased. This review summarizes recent research progress in the effects of THS on genotoxicity, metabolism and early life development using cellular and animal models. We first reported that THS generated in laboratory systems caused significant DNA damage in human cell lines. Our finding that THS significantly induces oxidative base lesions has been confirmed in skin wounds of mice models exposed to THS. THS also induced metabolomic changes in human reproductive cell lines. Furthermore, we demonstrated that early exposure to THS not only negatively impacts body weight in both male and female mice, but also induces persistent changes to immunological parameters in peripheral blood in these mice. These results indicate that THS is genotoxic at realistic experimental doses and that there may be a window of susceptibility for some forms of cellular damage induced by THS.

Genomic damage induced by 1-MHz ultrasound in vitro.

PubMed

Udroiu, Ion; Marinaccio, Jessica; Bedini, Angelico; Giliberti, Claudia; Palomba, Raffaele; Sgura, Antonella

2018-01-01

Genotoxic effects of therapeutic ultrasound are poorly documented, when compared with the wide use of this physical agent. The aim of this work was to investigate the clastogenic and aneugenic potential of 1 MHz ultrasound, employing intensities (200 and 300 mW/cm 2 ) above the cavitational threshold, but in the range of those normally used in therapeutics. Both normal fibroblasts (AG01522) and tumoral cells (MCF-7) were sonicated. While no effects on viability were noted, significant increases of CREST-negative micronuclei (indicative of clastogenesis) and CREST-positive micronuclei (indicative of aneuploidy) were detected. Clastogenesis was confirmed by increases of γ-H2AX foci, while increases of spindle anomalies confirmed the induction of aneuploidy. Our results confirm previous works that showed ultrasound-induced DNA breakage. Moreover, our experiments show that the known effect of ultrasound-induced damage to microtubules is also able to damage the mitotic spindle and induce aneuploidy. On the overall, this work highlights the importance to further investigate the potential risks related to therapeutics US. Environ. Mol. Mutagen. 59:60-68, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Antineoplastic Effects of α-Santalol on Estrogen Receptor-Positive and Estrogen Receptor-Negative Breast Cancer Cells through Cell Cycle Arrest at G2/M Phase and Induction of Apoptosis

PubMed Central

Santha, Sreevidya; Bommareddy, Ajay; Rule, Brittny; Guillermo, Ruth; Kaushik, Radhey S.; Young, Alan; Dwivedi, Chandradhar

2013-01-01

Anticancer efficacy and the mechanism of action of α-santalol, a terpenoid isolated from sandalwood oil, were investigated in human breast cancer cells by using p53 wild-type MCF-7 cells as a model for estrogen receptor(ER)-positive and p53 mutated MDA-MB-231 cells as a model for ER-negative breast cancer. α-Santalol inhibited cell viability and proliferation in a concentration and time-dependent manner in both cells regardless of their ER and/or p53 status. However, α-santalol produced relatively less toxic effect on normal breast epithelial cell line, MCF-10A. It induced G2/M cell cycle arrest and apoptosis in both MCF-7 and MDA-MB-231 cells. Cell cycle arrest induced by α-santalol was associated with changes in the protein levels of BRCA1, Chk1, G2/M regulatory cyclins, Cyclin dependent kinases (CDKs), Cell division cycle 25B (Cdc25B), Cdc25C and Ser-216 phosphorylation of Cdc25C. An up-regulated expression of CDK inhibitor p21 along with suppressed expression of mutated p53 was observed in MDA-MB-231 cells treated with α-santalol. On the contrary, α-santalol did not increase the expression of wild-type p53 and p21 in MCF-7 cells. In addition, α-santalol induced extrinsic and intrinsic pathways of apoptosis in both cells with activation of caspase-8 and caspase-9. It led to the activation of the executioner caspase-6 and caspase-7 in α-santalol-treated MCF-7 cells and caspase-3 and caspase-6 in MDA-MB-231 cells along with strong cleavage of poly(ADP-ribose) polymerase (PARP) in both cells. Taken together, this study for the first time identified strong anti-neoplastic effects of α-santalol against both ER-positive and ER-negative breast cancer cells. PMID:23451128

Happiness increases verbal and spatial working memory capacity where sadness does not: Emotion, working memory and executive control.

PubMed

Storbeck, Justin; Maswood, Raeya

2016-08-01

The effects of emotion on working memory and executive control are often studied in isolation. Positive mood enhances verbal and impairs spatial working memory, whereas negative mood enhances spatial and impairs verbal working memory. Moreover, positive mood enhances executive control, whereas negative mood has little influence. We examined how emotion influences verbal and spatial working memory capacity, which requires executive control to coordinate between holding information in working memory and completing a secondary task. We predicted that positive mood would improve both verbal and spatial working memory capacity because of its influence on executive control. Positive, negative and neutral moods were induced followed by completing a verbal (Experiment 1) or spatial (Experiment 2) working memory operation span task to assess working memory capacity. Positive mood enhanced working memory capacity irrespective of the working memory domain, whereas negative mood had no influence on performance. Thus, positive mood was more successful holding information in working memory while processing task-irrelevant information, suggesting that the influence mood has on executive control supersedes the independent effects mood has on domain-specific working memory.

n-Butanol extract from Folium isatidis inhibits lipopolysaccharide-induced inflammatory cytokine production in macrophages and protects mice against lipopolysaccharide-induced endotoxic shock

PubMed Central

Jiang, Lili; Lu, Yili; Jin, Jiahui; Dong, Lili; Xu, Fengli; Chen, Shuangshuang; Wang, Zhanyue; Liang, Guang; Shan, Xiaoou

2015-01-01

Sepsis, which is caused by severe infection, is an important cause of mortality, but effective clinical treatment against sepsis is extremely limited. As the main component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) plays a major role in inflammatory responses. Studies have shown beneficial pharmacological effects for Folium isatidis. The present study further illuminated the effects of n-butanol extract from Folium isatidis in LPS-induced septic shock and identified the main active chemical components. Our study showed that pretreatment with n-butanol extract from Folium isatidis not only significantly inhibited LPS-induced tumor necrosis factor-α and interleukin-6 production but also markedly and dose dependently enhanced the recruitment of MyD88, the phosphorylation of extracellular signal-regulated kinase, and the degradation of IκB-α. Additionally, the extract exhibited dramatic protective effects against lung injury and death in mice with septic shock. Eight main active compounds were identified, including organic acids, glycoside, indolinones, and flavonoids. These findings provide a perspective on the respiratory protection offered by n-butanol extract from Folium isatidis in LPS-induced sepsis and outline a novel therapeutic strategy for the treatment of sepsis. PMID:26491261

Regulation of hypoxia-induced autophagy in glioblastoma involves ATG9A.

PubMed

Abdul Rahim, Siti Aminah; Dirkse, Anne; Oudin, Anais; Schuster, Anne; Bohler, Jill; Barthelemy, Vanessa; Muller, Arnaud; Vallar, Laurent; Janji, Bassam; Golebiewska, Anna; Niclou, Simone P

2017-09-05

Hypoxia is negatively associated with glioblastoma (GBM) patient survival and contributes to tumour resistance. Anti-angiogenic therapy in GBM further increases hypoxia and activates survival pathways. The aim of this study was to determine the role of hypoxia-induced autophagy in GBM. Pharmacological inhibition of autophagy was applied in combination with bevacizumab in GBM patient-derived xenografts (PDXs). Sensitivity towards inhibitors was further tested in vitro under normoxia and hypoxia, followed by transcriptomic analysis. Genetic interference was done using ATG9A-depleted cells. We find that GBM cells activate autophagy as a survival mechanism to hypoxia, although basic autophagy appears active under normoxic conditions. Although single agent chloroquine treatment in vivo significantly increased survival of PDXs, the combination with bevacizumab resulted in a synergistic effect at low non-effective chloroquine dose. ATG9A was consistently induced by hypoxia, and silencing of ATG9A led to decreased proliferation in vitro and delayed tumour growth in vivo. Hypoxia-induced activation of autophagy was compromised upon ATG9A depletion. This work shows that inhibition of autophagy is a promising strategy against GBM and identifies ATG9 as a novel target in hypoxia-induced autophagy. Combination with hypoxia-inducing agents may provide benefit by allowing to decrease the effective dose of autophagy inhibitors.

Dominant negative mutant of ionotropic glutamate receptor subunit GluR3: implications for the role of a cysteine residue for its channel activity and pharmacological properties.

PubMed Central

Watase, K; Sekiguchi, M; Matsui, T A; Tagawa, Y; Wada, K

1997-01-01

We reported that a 33-amino-acid deletion (from tyrosine-715 to glycine-747) in a putative extracellular loop of GluR3 produced a mutant that exhibited dominant negative effects upon the functional expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors [Sekiguchi et al. (1994) J. Biol. Chem. 269, 14559-14565]. In this study, we searched for a key residue in the dominant negative effects to explore the mechanism and examined the role of the residue in the function of the AMPA receptor. We prepared 20 GluR3 mutants with amino acid substitutions within the 33-amino-acid-region, and dominant negative effects were tested electrophysiologically in Xenopus oocytes co-expressing the mutant and normal subunits. Among the mutants, only a GluR3 mutant in which an original cysteine (Cys)-722 was replaced by alanine exhibited a dominant negative effect comparable with that of the original mutant in which the entire 33-amino-acid segment is deleted. The co-expression of the Cys-722 mutant did not inhibit the translation of normal subunits in oocytes. The Cys-722 mutant formed a functional homomeric receptor with significantly higher affinity for glutamate or kainate than a homomeric GluR3 receptor. The Cys-722 mutation greatly enhanced the sensitivity of GluR3 for aniracetam, which alters kinetic properties of AMPA receptors. The kainate-induced currents in oocytes expressing the Cys-722 mutant alone showed strong inward rectification. These results suggest that the Cys-722 in GluR3 is important for dominant negative effects and plays a crucial role in the determination of pharmacological properties in AMPA receptor function. PMID:9065754