Feedback-induced glutamate spillover enhances negative feedback from horizontal cells to cones

NARCIS (Netherlands)

Vroman, Rozan; Kamermans, M.

2015-01-01

KEY POINTS: In the retina, horizontal cells feed back negatively to cone photoreceptors. Glutamate released from cones can spill over to neighbouring cones. Here we show that cone glutamate release induced by negative feedback can also spill over to neighbouring cones. This glutamate activates the

Feedback-induced glutamate spillover enhances negative feedback from horizontal cells to cones

NARCIS (Netherlands)

Vroman, Rozan; Kamermans, Maarten

2015-01-01

In the retina, horizontal cells feed back negatively to cone photoreceptors. Glutamate released from cones can spill over to neighbouring cones. Here we show that cone glutamate release induced by negative feedback can also spill over to neighbouring cones. This glutamate activates the glutamate

Negative plant-phyllosphere feedbacks in native Asteraceae hosts - a novel extension of the plant-soil feedback framework.

Science.gov (United States)

Whitaker, Briana K; Bauer, Jonathan T; Bever, James D; Clay, Keith

2017-08-01

Over the past 25 years, the plant-soil feedback (PSF) framework has catalyzed our understanding of how belowground microbiota impact plant fitness and species coexistence. Here, we apply a novel extension of this framework to microbiota associated with aboveground tissues, termed 'plant-phyllosphere feedback (PPFs)'. In parallel greenhouse experiments, rhizosphere and phyllosphere microbiota of con- and heterospecific hosts from four species were independently manipulated. In a third experiment, we tested the combined effects of soil and phyllosphere feedback under field conditions. We found that three of four species experienced weak negative PSF whereas, in contrast, all four species experienced strong negative PPFs. Field-based feedback estimates were highly negative for all four species, though variable in magnitude. Our results suggest that phyllosphere microbiota, like rhizosphere microbiota, can potentially mediate plant species coexistence via negative feedbacks. Extension of the PSF framework to the phyllosphere is needed to more fully elucidate plant-microbiota interactions. © 2017 John Wiley & Sons Ltd/CNRS.

A multiple relevance feedback strategy with positive and negative models.

Directory of Open Access Journals (Sweden)

Yunlong Ma

Full Text Available A commonly used strategy to improve search accuracy is through feedback techniques. Most existing work on feedback relies on positive information, and has been extensively studied in information retrieval. However, when a query topic is difficult and the results from the first-pass retrieval are very poor, it is impossible to extract enough useful terms from a few positive documents. Therefore, the positive feedback strategy is incapable to improve retrieval in this situation. Contrarily, there is a relatively large number of negative documents in the top of the result list, and it has been confirmed that negative feedback strategy is an important and useful way for adapting this scenario by several recent studies. In this paper, we consider a scenario when the search results are so poor that there are at most three relevant documents in the top twenty documents. Then, we conduct a novel study of multiple strategies for relevance feedback using both positive and negative examples from the first-pass retrieval to improve retrieval accuracy for such difficult queries. Experimental results on these TREC collections show that the proposed language model based multiple model feedback method which is generally more effective than both the baseline method and the methods using only positive or negative model.

Transcriptional feedback regulation of YUCCA genes in response to auxin levels in Arabidopsis.

Science.gov (United States)

Suzuki, Masashi; Yamazaki, Chiaki; Mitsui, Marie; Kakei, Yusuke; Mitani, Yuka; Nakamura, Ayako; Ishii, Takahiro; Soeno, Kazuo; Shimada, Yukihisa

2015-08-01

The IPyA pathway, the major auxin biosynthesis pathway, is transcriptionally regulated through a negative feedback mechanism in response to active auxin levels. The phytohormone auxin plays an important role in plant growth and development, and levels of active free auxin are determined by biosynthesis, conjugation, and polar transport. Unlike conjugation and polar transport, little is known regarding the regulatory mechanism of auxin biosynthesis. We discovered that expression of genes encoding indole-3-pyruvic acid (IPyA) pathway enzymes is regulated by elevated or reduced active auxin levels. Expression levels of TAR2, YUC1, YUC2, YUC4, and YUC6 were downregulated in response to synthetic auxins [1-naphthaleneacetic acid (NAA) and 2,4-dichlorophenoxyacetic acid (2,4-D)] exogenously applied to Arabidopsis thaliana L. seedlings. Concomitantly, reduced levels of endogenous indole-3-acetic acid (IAA) were observed. Alternatively, expression of these YUCCA genes was upregulated by the auxin biosynthetic inhibitor kynurenine in Arabidopsis seedlings, accompanied by reduced IAA levels. These results indicate that expression of YUCCA genes is regulated by active auxin levels. Similar results were also observed in auxin-overproduction and auxin-deficient mutants. Exogenous application of IPyA to Arabidopsis seedlings preincubated with kynurenine increased endogenous IAA levels, while preincubation with 2,4-D reduced endogenous IAA levels compared to seedlings exposed only to IPyA. These results suggest that in vivo conversion of IPyA to IAA was enhanced under reduced auxin levels, while IPyA to IAA conversion was depressed in the presence of excess auxin. Based on these results, we propose that the IPyA pathway is transcriptionally regulated through a negative feedback mechanism in response to active auxin levels.

Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM

International Nuclear Information System (INIS)

Lee, Eun Jin; Kang, Young Cheol; Park, Wook-Ha; Jeong, Jae Hoon; Pak, Youngmi Kim

2014-01-01

Highlights: • TFAM localizes in nuclei and mitochondria of neuronal cells. • Nuclear TFAM does not bind the Tfam promoter. • Nuclear TFAM reduced the Tfam promoter activity via suppressing NRF-1 activity. • A novel self-negative feedback regulation of Tfam gene expression is explored. • FAM may play different roles depending on its subcellular localizations. - Abstract: The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated that TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations

Adaptive disengagement buffers self-esteem from negative social feedback.

Science.gov (United States)

Leitner, Jordan B; Hehman, Eric; Deegan, Matthew P; Jones, James M

2014-11-01

The degree to which self-esteem hinges on feedback in a domain is known as a contingency of self-worth, or engagement. Although previous research has conceptualized engagement as stable, it would be advantageous for individuals to dynamically regulate engagement. The current research examined whether the tendency to disengage from negative feedback accounts for variability in self-esteem. We created the Adaptive Disengagement Scale (ADS) to capture individual differences in the tendency to disengage self-esteem from negative outcomes. Results demonstrated that the ADS is reliable and valid (Studies 1 and 2). Furthermore, in response to negative social feedback, higher scores on the ADS predicted greater state self-esteem (Study 3), and this relationship was mediated by disengagement (Study 4). These findings demonstrate that adaptive disengagement protects self-esteem from negative outcomes and that the ADS is a valid measure of individual differences in the implementation of this process. © 2014 by the Society for Personality and Social Psychology, Inc.

Comparing the effects of positive and negative feedback in information-integration category learning.

Science.gov (United States)

Freedberg, Michael; Glass, Brian; Filoteo, J Vincent; Hazeltine, Eliot; Maddox, W Todd

2017-01-01

Categorical learning is dependent on feedback. Here, we compare how positive and negative feedback affect information-integration (II) category learning. Ashby and O'Brien (2007) demonstrated that both positive and negative feedback are required to solve II category problems when feedback was not guaranteed on each trial, and reported no differences between positive-only and negative-only feedback in terms of their effectiveness. We followed up on these findings and conducted 3 experiments in which participants completed 2,400 II categorization trials across three days under 1 of 3 conditions: positive feedback only (PFB), negative feedback only (NFB), or both types of feedback (CP; control partial). An adaptive algorithm controlled the amount of feedback given to each group so that feedback was nearly equated. Using different feedback control procedures, Experiments 1 and 2 demonstrated that participants in the NFB and CP group were able to engage II learning strategies, whereas the PFB group was not. Additionally, the NFB group was able to achieve significantly higher accuracy than the PFB group by Day 3. Experiment 3 revealed that these differences remained even when we equated the information received on feedback trials. Thus, negative feedback appears significantly more effective for learning II category structures. This suggests that the human implicit learning system may be capable of learning in the absence of positive feedback.

Dissociation between active and observational learning from positive and negative feedback in Parkinsonism.

Science.gov (United States)

Kobza, Stefan; Ferrea, Stefano; Schnitzler, Alfons; Pollok, Bettina; Südmeyer, Martin; Bellebaum, Christian

2012-01-01

Feedback to both actively performed and observed behaviour allows adaptation of future actions. Positive feedback leads to increased activity of dopamine neurons in the substantia nigra, whereas dopamine neuron activity is decreased following negative feedback. Dopamine level reduction in unmedicated Parkinson's Disease patients has been shown to lead to a negative learning bias, i.e. enhanced learning from negative feedback. Recent findings suggest that the neural mechanisms of active and observational learning from feedback might differ, with the striatum playing a less prominent role in observational learning. Therefore, it was hypothesized that unmedicated Parkinson's Disease patients would show a negative learning bias only in active but not in observational learning. In a between-group design, 19 Parkinson's Disease patients and 40 healthy controls engaged in either an active or an observational probabilistic feedback-learning task. For both tasks, transfer phases aimed to assess the bias to learn better from positive or negative feedback. As expected, actively learning patients showed a negative learning bias, whereas controls learned better from positive feedback. In contrast, no difference between patients and controls emerged for observational learning, with both groups showing better learning from positive feedback. These findings add to neural models of reinforcement-learning by suggesting that dopamine-modulated input to the striatum plays a minor role in observational learning from feedback. Future research will have to elucidate the specific neural underpinnings of observational learning.

Enhanced Feedback-Related Negativity in Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

Shuhei Yamaguchi

2017-04-01

Full Text Available Alzheimer’s disease (AD, the most common cause of dementia in the elderly, results in the impairment of executive function, including that of performance monitoring. Feedback-related negativity (FRN is an electrophysiological measure reflecting the activity of this monitoring system via feedback signals, and is generated from the anterior cingulate cortex. However, there have been no reports on FRN in AD. Based on prior aging studies, we hypothesized that FRN would decrease in AD patients. To assess this, FRN was measured in healthy individuals and those with AD during a simple gambling task involving positive and negative feedback stimuli. Contrary to our hypothesis, FRN amplitude increased in AD patients, compared with the healthy elderly. We speculate that this may reflect the existence of a compensatory mechanism against the decline in executive function. Also, there was a significant association between FRN amplitude and depression scores in AD, and the FRN amplitude tended to increase insomuch as the Self-rating Depression Scale (SDS was higher. This result suggests the existence of a negative bias in the affective state in AD. Thus, the impaired functioning monitoring system in AD is a more complex phenomenon than we thought.

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

Directory of Open Access Journals (Sweden)

Duchu Chen

2016-01-01

Full Text Available 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.

Stereotype threat engenders neural attentional bias toward negative feedback to undermine performance.

Science.gov (United States)

Forbes, Chad E; Leitner, Jordan B

2014-10-01

Stereotype threat, a situational pressure individuals experience when they fear confirming a negative group stereotype, engenders a cascade of physiological stress responses, negative appraisals, and performance monitoring processes that tax working memory resources necessary for optimal performance. Less is known, however, about how stereotype threat biases attentional processing in response to performance feedback, and how such attentional biases may undermine performance. Women received feedback on math problems in stereotype threatening compared to stereotype-neutral contexts while continuous EEG activity was recorded. Findings revealed that stereotype threatened women elicited larger midline P100 ERPs, increased phase locking between anterior cingulate cortex and dorsolateral prefrontal cortex (two regions integral for attentional processes), and increased power in left fusiform gyrus in response to negative feedback compared to positive feedback and women in stereotype-neutral contexts. Increased power in left fusiform gyrus in response to negative feedback predicted underperformance on the math task among stereotype threatened women only. Women in stereotype-neutral contexts exhibited the opposite trend. Findings suggest that in stereotype threatening contexts, neural networks integral for attention and working memory are biased toward negative, stereotype confirming feedback at very early speeds of information processing. This bias, in turn, plays a role in undermining performance. Copyright © 2014 Elsevier B.V. All rights reserved.

Negative feedback enables fast and flexible collective decision-making in ants.

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Christoph Grüter

Full Text Available Positive feedback plays a major role in the emergence of many collective animal behaviours. In many ants pheromone trails recruit and direct nestmate foragers to food sources. The strong positive feedback caused by trail pheromones allows fast collective responses but can compromise flexibility. Previous laboratory experiments have shown that when the environment changes, colonies are often unable to reallocate their foragers to a more rewarding food source. Here we show both experimentally, using colonies of Lasius niger, and with an agent-based simulation model, that negative feedback caused by crowding at feeding sites allows ant colonies to maintain foraging flexibility even with strong recruitment to food sources. In a constant environment, negative feedback prevents the frequently found bias towards one feeder (symmetry breaking and leads to equal distribution of foragers. In a changing environment, negative feedback allows a colony to quickly reallocate the majority of its foragers to a superior food patch that becomes available when foraging at an inferior patch is already well underway. The model confirms these experimental findings and shows that the ability of colonies to switch to a superior food source does not require the decay of trail pheromones. Our results help to resolve inconsistencies between collective foraging patterns seen in laboratory studies and observations in the wild, and show that the simultaneous action of negative and positive feedback is important for efficient foraging in mass-recruiting insect colonies.

The light cycle controls the hatching rhythm in Bombyx mori via negative feedback loop of the circadian oscillator.

Science.gov (United States)

Tao, Hui; Li, Xue; Qiu, Jian-Feng; Liu, Heng-Jiang; Zhang, Da-Yan; Chu, Feng; Sima, Yanghu; Xu, Shi-Qing

2017-10-01

Hatching behavior is a key target in silkworm (Bombyx mori) rearing, especially for the control of Lepidoptera pests. According to previous research, hatching rhythms appear to be controlled by a clock mechanism that restricts or "gates" hatching to a particular time. However, the underlying mechanism remains elusive. Under 12-h light:12-h dark photoperiod (LD) conditions, the transcriptional levels of the chitinase5 (Cht5) and hatching enzyme-like (Hel) genes, as well as the enzymatic activities of their gene products, oscillated in time with ambient light cycles, as did the transcriptional levels of the cryptochrome 1, cryptochrome 2, period (per), and timeless genes, which are key components of the negative feedback loop of the circadian rhythm. These changes were related to the expression profile of the ecdysteroid receptor gene and the hatching behavior of B. mori eggs. However, under continuous light or dark conditions, the hatching behavior, the expression levels of Cht5 and Hel, as well as the enzymatic activities of their gene products, were not synchronized unlike under LD conditions. In addition, immunohistochemistry experiments showed that light promoted the translocation of PER from the cytoplasm to the nucleus. In conclusion, LD cycles regulate the hatching rhythm of B. mori via negative feedback loop of the circadian oscillator. © 2017 Wiley Periodicals, Inc.

Interrogative pressure in simulated forensic interviews: the effects of negative feedback.

Science.gov (United States)

McGroarty, Allan; Baxter, James S

2007-08-01

Much experimental research on interrogative pressure has concentrated on the effects of leading questions, and the role of feedback in influencing responses in the absence of leading questions has been neglected by comparison. This study assessed the effect of negative feedback and the presence of a second interviewer on interviewee responding in simulated forensic interviews. Participants viewed a videotape of a crime, answered questions about the clip and were requestioned after receiving feedback. Compared with neutral feedback, negative feedback resulted in more response changes, higher reported state anxiety and higher ratings of interview difficulty. These results are consistent with Gudjonsson and Clark's (1986) model of interrogative suggestibility. The presence and involvement of a second interviewer did not significantly affect interviewee responding, although trait anxiety scores were elevated when a second interviewer was present. The theoretical and applied implications of these findings are considered.

Lyapunov-based Stability of Feedback Interconnections of Negative Imaginary Systems

KAUST Repository

Ghallab, Ahmed G.

2017-10-19

Feedback control systems using sensors and actuators such as piezoelectric sensors and actuators, micro-electro-mechanical systems (MEMS) sensors and opto-mechanical sensors, are allowing new advances in designing such high precision technologies. The negative imaginary control systems framework allows for robust control design for such high precision systems in the face of uncertainties due to unmodelled dynamics. The stability of the feedback interconnection of negative imaginary systems has been well established in the literature. However, the proofs of stability feedback interconnection which are used in some previous papers have a shortcoming due to a matrix inevitability issue. In this paper, we provide a new and correct Lyapunov-based proof of one such result and show that the result is still true.

Lyapunov-based Stability of Feedback Interconnections of Negative Imaginary Systems

KAUST Repository

Ghallab, Ahmed G.; Mabrok, Mohamed; Petersen, Ian R.

2017-01-01

Feedback control systems using sensors and actuators such as piezoelectric sensors and actuators, micro-electro-mechanical systems (MEMS) sensors and opto-mechanical sensors, are allowing new advances in designing such high precision technologies. The negative imaginary control systems framework allows for robust control design for such high precision systems in the face of uncertainties due to unmodelled dynamics. The stability of the feedback interconnection of negative imaginary systems has been well established in the literature. However, the proofs of stability feedback interconnection which are used in some previous papers have a shortcoming due to a matrix inevitability issue. In this paper, we provide a new and correct Lyapunov-based proof of one such result and show that the result is still true.

Anger and attitudinal reactions to negative feedback: The effects of emotional instability and power

NARCIS (Netherlands)

Niemann, Jana; Wisse, Barbara; Rus, Diana; Van Yperen, Nico W.; Sassenberg, Kai

2014-01-01

Feedback is a basic tool that is used to stimulate learning and performance at all organizational levels. However, negative feedback can sometimes evoke defensive responses such as feelings of anger or the repudiation of the feedback. In two experiments we explored whether people’s negating

A novel approach to negative feedback in RX front-ends

DEFF Research Database (Denmark)

Vandi, Luca; Andreani, Pietro; Tired, Tobias

2006-01-01

A new approach to negative feedback is proposed and applied to active mixer cells based on Gilbert multiplier. The feedback can be exploited in several ways, and different configurations are derived. A dual-loop topology provides a solution for inductor-less broad-band receiver stages. The nature...

Negative feedback and adaptive resistance to the targeted therapy of cancer

OpenAIRE

Chandarlapaty, Sarat

2012-01-01

Mutational activation of growth factor signaling pathways is commonly observed and often necessary for oncogenic transformation. Under physiologic conditions, these pathways are subject to tight regulation via negative feedback which limits the extent and duration of signaling events after physiologic stimulation. Until recently, the role of these negative feedback pathways in oncogene driven cancers has been poorly understood. In this review, I will discuss the evidence for the existence and...

Evaluating the negative or valuing the positive? Neural mechanisms supporting feedback-based learning across development.

Science.gov (United States)

van Duijvenvoorde, Anna C K; Zanolie, Kiki; Rombouts, Serge A R B; Raijmakers, Maartje E J; Crone, Eveline A

2008-09-17

How children learn from positive and negative performance feedback lies at the foundation of successful learning and is therefore of great importance for educational practice. In this study, we used functional magnetic resonance imaging (fMRI) to examine the neural developmental changes related to feedback-based learning when performing a rule search and application task. Behavioral results from three age groups (8-9, 11-13, and 18-25 years of age) demonstrated that, compared with adults, 8- to 9-year-old children performed disproportionally more inaccurately after receiving negative feedback relative to positive feedback. Additionally, imaging data pointed toward a qualitative difference in how children and adults use performance feedback. That is, dorsolateral prefrontal cortex and superior parietal cortex were more active after negative feedback for adults, but after positive feedback for children (8-9 years of age). For 11- to 13-year-olds, these regions did not show differential feedback sensitivity, suggesting that the transition occurs around this age. Pre-supplementary motor area/anterior cingulate cortex, in contrast, was more active after negative feedback in both 11- to 13-year-olds and adults, but not 8- to 9-year-olds. Together, the current data show that cognitive control areas are differentially engaged during feedback-based learning across development. Adults engage these regions after signals of response adjustment (i.e., negative feedback). Young children engage these regions after signals of response continuation (i.e., positive feedback). The neural activation patterns found in 11- to 13-year-olds indicate a transition around this age toward an increased influence of negative feedback on performance adjustment. This is the first developmental fMRI study to compare qualitative changes in brain activation during feedback learning across distinct stages of development.

Negative Feedback for Small Capacitive Touchscreen Interfaces: A Usability Study for Data Entry Tasks.

Science.gov (United States)

Parikh, S P; Esposito, J M

2012-01-01

Touchscreen technology has become pervasive in the consumer product arena over the last decade, offering some distinct advantages such as software reconfigurable interfaces and the removal of space consuming mice and keyboards. However, there are significant drawbacks to these devices that have limited their adoption by some users. Most notably, standard touchscreens demand the user's visual attention and require them to look at the input device to avoid pressing the wrong button. This issue is particularly important for mobile, capacitive sensing, nonstylus devices, such as the iPhone where small button sizes can generate high error rates. While previous work has shown the benefits of augmenting such interfaces with audio or vibrotactile feedback, only positive feedback (confirmation of button presses) has been considered. In this paper, we present a simple prototype interface that provides negative vibrotactile feedback. By negative, we mean feedback is generated when an inactive or ambiguous part of the screen, such as the area between two buttons, is touched. First, we present a usability study comparing positive and negative vibrotactile feedback for a benchmark numerical data entry task. The difference in performance is not statistically significant, implying negative feedback provides comparable benefits. Next, based on the experimenter's observations and the users comments, we introduce a multimodal feedback strategy-combining complementary positive audio and negative vibrotactile signals. User tests on a text entry experiment show that, with multimodal feedback, users exhibit a (statistically significant) 24 percent reduction in corrective key presses, as compared to positive audio feedback alone. Exit survey comments indicate that users favor multimodal feedback.

Learning from Negative Feedback in Patients with Major Depressive Disorder is Attenuated by SSRI Antidepressants

Directory of Open Access Journals (Sweden)

Mohammad M. Herzallah

2013-09-01

Full Text Available One barrier to interpreting past studies of cognition and Major Depressive Disorder (MDD has been the failure in many studies to adequately dissociate the effects of MDD from the potential cognitive side effects of Selective Serotonin Reuptake Inhibitors (SSRI use. To better understand how remediation of depressive symptoms affects cognitive function in MDD, we evaluated three groups of subjects: medication-naïve patients with MDD, medicated patients with MDD receiving the SSRI paroxetine and healthy control subjects. All were administered a category-learning task that allows for dissociation between learning from positive feedback (reward versus learning from negative feedback (punishment. Healthy subjects learned significantly better from positive feedback than medication-naïve and medicated MDD groups, whose learning accuracy did not differ significantly. In contrast, medicated patients with MDD learned significantly less from negative feedback than medication-naïve patients with MDD and healthy subjects, whose learning accuracy was comparable. A comparison of subject’s relative sensitivity to positive versus negative feedback showed that both the medicated MDD and healthy control groups conform to Kahneman and Tversky’s (1979 Prospect Theory, which expects losses (negative feedback to loom psychologically slightly larger than gains (positive feedback. However, medicated MDD and HC profiles are not similar, which indicates that the state of medicated MDD is not ‘normal’ when compared to HC, but rather balanced with less learning from both positive and negative feedback. On the other hand, medication-naïve patients with MDD violate Prospect Theory by having significantly exaggerated learning from negative feedback. This suggests that SSRI antidepressants impair learning from negative feedback, while having negligible effect on learning from positive feedback. Overall, these findings shed light on the importance of dissociating the

Negative Plant-Soil Feedback and Positive Species Interaction in a Herbaceous Plant Community

NARCIS (Netherlands)

Bonanomi, G.; Rietkerk, M.; Dekker, S.C.; Mazzoleni, S.

2005-01-01

Increasing evidence shows that facilitative interaction and negative plant¿soil feedback are driving factors of plant population dynamics and community processes. We studied the intensity and the relative impact of negative feedback on clonal growth and seed germination of Scirpus holoschoenus, a

Negative Plant–Soil Feedback and Positive Species Interaction in a Herbaceous Plant Community

NARCIS (Netherlands)

Bonanomi, G.; Rietkerk, M.G.; Dekker, S.C.; Mazzoleni, S.

2005-01-01

Increasing evidence shows that facilitative interaction and negative plant–soil feedback are driving factors of plant population dynamics and community processes. We studied the intensity and the relative impact of negative feedback on clonal growth and seed germination of Scirpus holoschoenus, a

Physical limits of feedback noise-suppression in biological networks

International Nuclear Information System (INIS)

Zhang, Jiajun; Yuan, Zhanjiang; Zhou, Tianshou

2009-01-01

Feedback is a ubiquitous control mechanism of biological networks, and has also been identified in a variety of regulatory systems and organisms. It has been shown that, for a given gain and with negligible intrinsic noise, negative feedback impairs noise buffering whereas positive feedback enhances noise buffering. We further investigate the influence of negative and positive feedback on noise in output signals by considering both intrinsic and extrinsic noise as well as operator noise. We find that, while maintaining the system sensitivity, either there exists a minimum of the output noise intensity corresponding to a biologically feasible feedback strength, or the output noise intensity is a monotonic function of feedback strength bounded by both biological and dynamical constraints. In both cases, feedback noise-suppression is physically limited. In other words, noise suppressed by negative or positive feedback cannot be reduced without limitation even in the case of slow transcription

Reciprocal, Longitudinal Associations among Adolescents' Negative Feedback-Seeking, Depressive Symptoms, and Peer Relations

Science.gov (United States)

Borelli, Jessica L.; Prinstein, Mitchell J.

2006-01-01

This study examined reciprocal associations among adolescents' negative feedback-seeking, depressive symptoms, perceptions of friendship quality, and peer-reported social preference over an 11-month period. A total of 478 adolescents in grades 6-8 completed measures of negative feedback-seeking, depressive symptoms, friendship quality,…

Relationship between Counseling Students' Childhood Memories and Current Negative Self-Evaluations When Receiving Corrective Feedback

Science.gov (United States)

Stroud, Daniel; Olguin, David; Marley, Scott

2016-01-01

This article entails a study focused on the relationship between counseling students' negative childhood memories of receiving corrective feedback and current negative self-evaluations when receiving similar feedback in counselor education programs. Participants (N = 186) completed the Corrective Feedback Instrument-Revised (CFI-R; Hulse-Killacky…

A Theory of Circular Organization and Negative Feedback: Defining Life in a Cybernetic Context

Science.gov (United States)

Tsokolov, Sergey

2010-12-01

All life today incorporates a variety of systems controlled by negative feedback loops and sometimes amplified by positive feedback loops. The first forms of life necessarily also required primitive versions of feedback, yet surprisingly little emphasis has been given to the question of how feedback emerged out of primarily chemical systems. One chemical system has been established that spontaneously develops autocatalytic feedback, the Belousov-Zhabotinsky (BZ) reaction. In this essay, I discuss the BZ reaction as a possible model for similar reactions that could have occurred under prebiotic Earth conditions. The main point is that the metabolism of contemporary life evolved from primitive homeostatic networks regulated by negative feedback. Because life could not exist in their absence, feedback loops should be included in definitions of life.

The power of negative feedback from an artificial agent to promote energy saving behavior

NARCIS (Netherlands)

Midden, Cees; Ham, Jaap; Marcus, A.

2014-01-01

In this paper we analyze the role of negative feedback as provided by artificial agents. We examine the hypothesis that negative feedback offers substantial potential to enhance persuasive interventions aimed to change behavior. This hypothesis is tested based on a review of several studies using

The combination of positive and negative feedback loops confers exquisite flexibility to biochemical switches

International Nuclear Information System (INIS)

Pfeuty, Benjamin; Kaneko, Kunihiko

2009-01-01

A wide range of cellular processes require molecular regulatory pathways to convert a graded signal into a discrete response. One prevalent switching mechanism relies on the coexistence of two stable states (bistability) caused by positive feedback regulations. Intriguingly, positive feedback is often supplemented with negative feedback, raising the question of whether and how these two types of feedback can cooperate to control discrete cellular responses. To address this issue, we formulate a canonical model of a protein–protein interaction network and analyze the dynamics of a prototypical two-component circuit. The appropriate combination of negative and positive feedback loops can bring a bistable circuit close to the oscillatory regime. Notably, sharply activated negative feedback can give rise to a bistable regime wherein two stable fixed points coexist and may collide pairwise with two saddle points. This specific type of bistability is found to allow for separate and flexible control of switch-on and switch-off events, for example (i) to combine fast and reversible transitions, (ii) to enable transient switching responses and (iii) to display tunable noise-induced transition rates. Finally, we discuss the relevance of such bistable switching behavior, and the circuit topologies considered, to specific biological processes such as adaptive metabolic responses, stochastic fate decisions and cell-cycle transitions. Taken together, our results suggest an efficient mechanism by which positive and negative feedback loops cooperate to drive the flexible and multifaceted switching behaviors arising in biological systems

A Novel TetR Family Transcriptional Regulator, CalR3, Negatively Controls Calcimycin Biosynthesis in Streptomyces chartreusis NRRL 3882

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Lixia Gou

2017-11-01

Full Text Available Calcimycin is a unique ionophoric antibiotic that is widely used in biochemical and pharmaceutical applications, but the genetic basis underlying the regulatory mechanisms of calcimycin biosynthesis are unclear. Here, we identified the calR3 gene, which encodes a novel TetR family transcriptional regulator and exerts a negative effect on calcimycin biosynthesis. Disruption of calR3 in Streptomyces chartreusis NRRL 3882 led to significantly increased calcimycin and its intermediate cezomycin. Gene expression analysis showed that the transcription of calR3 and its adjacent calT gene were dramatically enhanced (30- and 171-fold, respectively in GLX26 (ΔcalR3 mutants compared with the wild-type strains. Two CalR3-binding sites within the bidirectional calR3-calT promoter region were identified using a DNase I footprinting assay, indicating that CalR3 directly repressed the transcription of its own gene and the calT gene. In vitro electrophoretic mobility shift assays suggested that both calcimycin and cezomycin can act as CalR3 ligands to induce CalR3 to dissociate from its binding sites. These findings indicate negative feedback for the regulation of CalR3 in calcimycin biosynthesis and suggest that calcimycin production can be improved by manipulating its biosynthetic machinery.

Interrogation of inhibitor of nuclear factor κB α/nuclear factor κB (IκBα/NF-κB) negative feedback loop dynamics: from single cells to live animals in vivo.

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Moss, Britney L; Elhammali, Adnan; Fowlkes, Tiffanie; Gross, Shimon; Vinjamoori, Anant; Contag, Christopher H; Piwnica-Worms, David

2012-09-07

Full understanding of the biological significance of negative feedback processes requires interrogation at multiple scales as follows: in single cells, cell populations, and live animals in vivo. The transcriptionally coupled IκBα/NF-κB negative feedback loop, a pivotal regulatory node of innate immunity and inflammation, represents a model system for multiscalar reporters. Using a κB(5)→IκBα-FLuc bioluminescent reporter, we rigorously evaluated the dynamics of ΙκBα degradation and subsequent NF-κB transcriptional activity in response to diverse modes of TNFα stimulation. Modulating TNFα concentration or pulse duration yielded complex, reproducible, and differential ΙκBα dynamics in both cell populations and live single cells. Tremendous heterogeneity in the transcriptional amplitudes of individual responding cells was observed, which was greater than the heterogeneity in the transcriptional kinetics of responsive cells. Furthermore, administration of various TNFα doses in vivo generated ΙκBα dynamic profiles in the liver resembling those observed in single cells and populations of cells stimulated with TNFα pulses. This suggested that dose modulation of circulating TNFα was perceived by hepatocytes in vivo as pulses of increasing duration. Thus, a robust bioluminescent reporter strategy enabled rigorous quantitation of NF-κB/ΙκBα dynamics in both live single cells and cell populations and furthermore, revealed reproducible behaviors that informed interpretation of in vivo studies.

Feeling Better About Self After Receiving Negative Feedback: When the Sense That Ability Can Be Improved Is Activated.

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Hu, Xinyi; Chen, Yinghe; Tian, Baowei

2016-01-01

Past studies suggest that managers and educators often consider negative feedback as a motivator for individuals to think about their shortcomings and improve their work, but delivering negative feedback does not always achieve desired results. The present study, based on incremental theory, employed an intervention method to activate the belief that a particular ability could be improved after negative feedback. Three experiments tested the intervention effect on negative self-relevant emotion. Study 1 indicated conveying suggestions for improving ability reduced negative self-relevant emotion after negative feedback. Study 2 tested whether activating the sense of possible improvement in the ability could reduce negative self-relevant emotion. Results indicated activating the belief that ability could be improved reduced negative self-relevant emotion after failure, but delivering emotion management information alone did not yield the same effect. Study 3 extended the results by affirming the effort participants made in doing the test, and found the affirmation reduced negative self-relevant emotion. Collectively, the findings indicated focusing on the belief that the ability could be improved in the future can reduce negative self-relevant emotion after negative feedback.

Managing Written and Oral Negative Feedback in a Synchronous Online Teaching Situation

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Guichon, Nicolas; Betrancourt, Mireille; Prie, Yannick

2012-01-01

This case study focuses on the feedback that is provided by tutors to learners in the course of synchronous online teaching. More specifically, we study how trainee tutors used the affordances of Visu, an experimental web videoconferencing system, to provide negative feedback. Visu features classical functionalities such as video and chat, and it…

Negative plant-soil feedbacks increase with plant abundance, and are unchanged by competition.

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Maron, John L; Laney Smith, Alyssa; Ortega, Yvette K; Pearson, Dean E; Callaway, Ragan M

2016-08-01

Plant-soil feedbacks and interspecific competition are ubiquitous interactions that strongly influence the performance of plants. Yet few studies have examined whether the strength of these interactions corresponds with the abundance of plant species in the field, or whether feedbacks and competition interact in ways that either ameliorate or exacerbate their effects in isolation. We sampled soil from two intermountain grassland communities where we also measured the relative abundance of plant species. In greenhouse experiments, we quantified the direction and magnitude of plant-soil feedbacks for 10 target species that spanned a range of abundances in the field. In soil from both sites, plant-soil feedbacks were mostly negative, with more abundant species suffering greater negative feedbacks than rare species. In contrast, the average response to competition for each species was unrelated with its abundance in the field. We also determined how competitive response varied among our target species when plants competed in live vs. sterile soil. Interspecific competition reduced plant size, but the strength of this negative effect was unchanged by plant-soil feedbacks. Finally, when plants competed interspecifically, we asked how conspecific-trained, heterospecific-trained, and sterile soil influenced the competitive responses of our target species and how this varied depending on whether target species were abundant or rare in the field. Here, we found that both abundant and rare species were not as harmed by competition when they grew in heterospecific-trained soil compared to when they grew in conspecific-cultured soil. Abundant species were also not as harmed by competition when growing in sterile vs. conspecific-trained soil, but this was not the case for rare species. Our results suggest that abundant plants accrue species-specific soil pathogens to a greater extent than rare species. Thus, negative feedbacks may be critical for preventing abundant species from

Valproic acid disrupts the oscillatory expression of core circadian rhythm transcription factors.

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Griggs, Chanel A; Malm, Scott W; Jaime-Frias, Rosa; Smith, Catharine L

2018-01-15

Valproic acid (VPA) is a well-established therapeutic used in treatment of seizure and mood disorders as well as migraines and a known hepatotoxicant. About 50% of VPA users experience metabolic disruptions, including weight gain, hyperlipidemia, and hyperinsulinemia, among others. Several of these metabolic abnormalities are similar to the effects of circadian rhythm disruption. In the current study, we examine the effect of VPA exposure on the expression of core circadian transcription factors that drive the circadian clock via a transcription-translation feedback loop. In cells with an unsynchronized clock, VPA simultaneously upregulated the expression of genes encoding core circadian transcription factors that regulate the positive and negative limbs of the feedback loop. Using low dose glucocorticoid, we synchronized cultured fibroblast cells to a circadian oscillatory pattern. Whether VPA was added at the time of synchronization or 12h later at CT12, we found that VPA disrupted the oscillatory expression of multiple genes encoding essential transcription factors that regulate circadian rhythm. Therefore, we conclude that VPA has a potent effect on the circadian rhythm transcription-translation feedback loop that may be linked to negative VPA side effects in humans. Furthermore, our study suggests potential chronopharmacology implications of VPA usage. Copyright © 2017. Published by Elsevier Inc.

Fear of negative evaluation modulates electrocortical and behavioral responses when anticipating social evaluative feedback

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Melle J.W. Van Der Molen

2014-01-01

Full Text Available Cognitive models posit that the fear of negative evaluation (FNE is a hallmark feature of social anxiety. As such, individuals with high FNE may show biased information processing when faced with social evaluation. The aim of the current study was to examine the neural underpinnings of anticipating and processing of social-evaluative feedback, and its correlates with FNE. We used a social judgment paradigm in which female participants (N=31 were asked to indicate whether they believed to be socially accepted or rejected by their peers. Anticipatory attention was indexed by the stimulus preceding negativity (SPN, while the feedback-related negativity and P3 were used to index the processing of social-evaluative feedback. Results provided evidence of an optimism bias in social peer evaluation, as participants more often predicted to be socially accepted than rejected. Participants with high levels of FNE needed more time to provide their judgments about the social-evaluative outcome. While anticipating social-evaluative feedback, SPN amplitudes were larger for anticipated social acceptance than for social rejection feedback. Interestingly, the SPN during anticipated social acceptance was larger in participants with high levels of FNE. None of the feedback-related brain potentials correlated with the FNE. Together, the results provide evidence of biased information processing in individuals with high levels of FNE when anticipating (rather than processing social-evaluative feedback. The delayed response times in high FNE individuals were interpreted to reflect augmented vigilance imposed by the upcoming social evaluative threat. Allegedly, the SPN constitutes a neural marker of this vigilance in females with higher FNE levels, particularly when anticipating social acceptance feedback.

Fear of negative evaluation modulates electrocortical and behavioral responses when anticipating social evaluative feedback

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Van der Molen, Melle J. W.; Poppelaars, Eefje S.; Van Hartingsveldt, Caroline T. A.; Harrewijn, Anita; Gunther Moor, Bregtje; Westenberg, P. Michiel

2014-01-01

Cognitive models posit that the fear of negative evaluation (FNE) is a hallmark feature of social anxiety. As such, individuals with high FNE may show biased information processing when faced with social evaluation. The aim of the current study was to examine the neural underpinnings of anticipating and processing social-evaluative feedback, and its correlates with FNE. We used a social judgment paradigm in which female participants (N = 31) were asked to indicate whether they believed to be socially accepted or rejected by their peers. Anticipatory attention was indexed by the stimulus preceding negativity (SPN), while the feedback-related negativity and P3 were used to index the processing of social-evaluative feedback. Results provided evidence of an optimism bias in social peer evaluation, as participants more often predicted to be socially accepted than rejected. Participants with high levels of FNE needed more time to provide their judgments about the social-evaluative outcome. While anticipating social-evaluative feedback, SPN amplitudes were larger for anticipated social acceptance than for social rejection feedback. Interestingly, the SPN during anticipated social acceptance was larger in participants with high levels of FNE. None of the feedback-related brain potentials correlated with the FNE. Together, the results provided evidence of biased information processing in individuals with high levels of FNE when anticipating (rather than processing) social-evaluative feedback. The delayed response times in high FNE individuals were interpreted to reflect augmented vigilance imposed by the upcoming social-evaluative threat. Possibly, the SPN constitutes a neural marker of this vigilance in females with higher FNE levels, particularly when anticipating social acceptance feedback. PMID:24478667

Modulation of dynamic modes by interplay between positive and negative feedback loops in gene regulatory networks

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Wang, Liu-Suo; Li, Ning-Xi; Chen, Jing-Jia; Zhang, Xiao-Peng; Liu, Feng; Wang, Wei

2018-04-01

A positive and a negative feedback loop can induce bistability and oscillation, respectively, in biological networks. Nevertheless, they are frequently interlinked to perform more elaborate functions in many gene regulatory networks. Coupled positive and negative feedback loops may exhibit either oscillation or bistability depending on the intensity of the stimulus in some particular networks. It is less understood how the transition between the two dynamic modes is modulated by the positive and negative feedback loops. We developed an abstract model of such systems, largely based on the core p53 pathway, to explore the mechanism for the transformation of dynamic behaviors. Our results show that enhancing the positive feedback may promote or suppress oscillations depending on the strength of both feedback loops. We found that the system oscillates with low amplitudes in response to a moderate stimulus and switches to the on state upon a strong stimulus. When the positive feedback is activated much later than the negative one in response to a strong stimulus, the system exhibits long-term oscillations before switching to the on state. We explain this intriguing phenomenon using quasistatic approximation. Moreover, early switching to the on state may occur when the system starts from a steady state in the absence of stimuli. The interplay between the positive and negative feedback plays a key role in the transitions between oscillation and bistability. Of note, our conclusions should be applicable only to some specific gene regulatory networks, especially the p53 network, in which both oscillation and bistability exist in response to a certain type of stimulus. Our work also underscores the significance of transient dynamics in determining cellular outcome.

Prospect theory does not describe the feedback-related negativity value function.

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Sambrook, Thomas D; Roser, Matthew; Goslin, Jeremy

2012-12-01

Humans handle uncertainty poorly. Prospect theory accounts for this with a value function in which possible losses are overweighted compared to possible gains, and the marginal utility of rewards decreases with size. fMRI studies have explored the neural basis of this value function. A separate body of research claims that prediction errors are calculated by midbrain dopamine neurons. We investigated whether the prospect theoretic effects shown in behavioral and fMRI studies were present in midbrain prediction error coding by using the feedback-related negativity, an ERP component believed to reflect midbrain prediction errors. Participants' stated satisfaction with outcomes followed prospect theory but their feedback-related negativity did not, instead showing no effect of marginal utility and greater sensitivity to potential gains than losses. Copyright © 2012 Society for Psychophysiological Research.

Feedback-related negativity in children with two subtypes of attention deficit hyperactivity disorder.

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Jingbo Gong

Full Text Available The current model of ADHD suggests abnormal reward and punishment sensitivity, although differences in ADHD subgroups are unclear. This study aimed to investigate the effect of feedback valence (reward or punishment and punishment magnitude (small or large on Feedback-Related Negativity (FRN and Late Positive Potential (LPP in two subtypes of ADHD (ADHD-C and ADHD-I compared to typically developing children (TD during a children's gambling task.Children with ADHD-C (n = 16, children with ADHD-I (n = 15 and typically developing children (n = 15 performed a children's gambling task under three feedback conditions: large losses, small losses and gains. FRN and LPP components in brain potentials were recorded and analyzed.In TD children and children with ADHD-C, large loss feedback evoked more negative FRN amplitudes than small loss feedback, suggesting that brain sensitivity to the punishment and its magnitude is not impaired in children with ADHD-C. In contrast to these two groups, the FRN effect was absent in children with ADHD-I. The LPP amplitudes were larger in children with ADHD-C in comparison with those with ADHD-I, regardless of feedback valence and magnitude.Children with ADHD-C exhibit intact brain sensitivity to punishment similar to TD children. In contrast, children with ADHD-I are significantly impaired in neural sensitivity to the feedback stimuli and in particular, to punishment, compared to TD and ADHD-C children. Thus, FRN, rather than LPP, is a reliable index of the difference in reward and punishment sensitivity across different ADHD-subcategories.

Mode Selection Rules for a Two-Delay System with Positive and Negative Feedback Loops

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Takahashi, Kin'ya; Kobayashi, Taizo

2018-04-01

The mode selection rules for a two-delay system, which has negative feedback with a short delay time t1 and positive feedback with a long delay time t2, are studied numerically and theoretically. We find two types of mode selection rules depending on the strength of the negative feedback. When the strength of the negative feedback |α1| (α1 0), 2m + 1-th harmonic oscillation is well sustained in a neighborhood of t1/t2 = even/odd, i.e., relevant condition. In a neighborhood of the irrelevant condition given by t1/t2 = odd/even or t1/t2 = odd/odd, higher harmonic oscillations are observed. However, if |α1| is slightly less than α2, a different mode selection rule works, where the condition t1/t2 = odd/even is relevant and the conditions t1/t2 = odd/odd and t1/t2 = even/odd are irrelevant. These mode selection rules are different from the mode selection rule of the normal two-delay system with two positive feedback loops, where t1/t2 = odd/odd is relevant and the others are irrelevant. The two types of mode selection rules are induced by individually different mechanisms controlling the Hopf bifurcation, i.e., the Hopf bifurcation controlled by the "boosted bifurcation process" and by the "anomalous bifurcation process", which occur for |α1| below and above the threshold value αth, respectively.

The price of soliciting and receiving negative feedback: self-verification theory as a vulnerability to depression theory.

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Joiner, T E

1995-05-01

The hypothesis that people who seek and receive negative feedback are vulnerable to increases in depressed symptoms was tested among 100 undergraduates and their roommates. Students and roommates completed questionnaires on their views of each other and on their own levels of negative feedback seeking, depressed and anxious symptoms, negative and positive affect, and self-esteem. Three weeks later, students and roommates completed the same questionnaires. Results were, in general, consistent with prediction. Students who reported an interest in their roommates' negative feedback and who lived with a roommate who viewed them negatively were at heightened risk for increases in depressed symptoms. These results could not be explained in terms of the variables' relations to trait self-esteem. The symptom specificity of the effect was moderately supported. Implications for work on interpersonal vulnerability to depression are discussed.

Impaired coupling of local and global functional feedbacks underlies abnormal synchronization and negative symptoms of schizophrenia.

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Noh, Kyungchul; Shin, Kyung Soon; Shin, Dongkwan; Hwang, Jae Yeon; Kim, June Sic; Jang, Joon Hwan; Chung, Chun Kee; Kwon, Jun Soo; Cho, Kwang-Hyun

2013-04-10

Abnormal synchronization of brain oscillations is found to be associated with various core symptoms of schizophrenia. However, the underlying mechanism of this association remains yet to be elucidated. In this study, we found that coupled local and global feedback (CLGF) circuits in the cortical functional network are related to the abnormal synchronization and also correlated to the negative symptom of schizophrenia. Analysis of the magnetoencephalography data obtained from patients with chronic schizophrenia during rest revealed an increase in beta band synchronization and a reduction in gamma band power compared to healthy controls. Using a feedback identification method based on non-causal impulse responses, we constructed functional feedback networks and found that CLGF circuits were significantly reduced in schizophrenia. From computational analysis on the basis of the Wilson-Cowan model, we unraveled that the CLGF circuits are critically involved in the abnormal synchronization and the dynamical switching between beta and gamma bands power in schizophrenia. Moreover, we found that the abundance of CLGF circuits was negatively correlated with the development of negative symptoms of schizophrenia, suggesting that the negative symptom is closely related to the impairment of this circuit. Our study implicates that patients with schizophrenia might have the impaired coupling of inter- and intra-regional functional feedbacks and that the CLGF circuit might serve as a critical bridge between abnormal synchronization and the negative symptoms of schizophrenia.

Feedback Valence Affects Auditory Perceptual Learning Independently of Feedback Probability

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Amitay, Sygal; Moore, David R.; Molloy, Katharine; Halliday, Lorna F.

2015-01-01

Previous studies have suggested that negative feedback is more effective in driving learning than positive feedback. We investigated the effect on learning of providing varying amounts of negative and positive feedback while listeners attempted to discriminate between three identical tones; an impossible task that nevertheless produces robust learning. Four feedback conditions were compared during training: 90% positive feedback or 10% negative feedback informed the participants that they were doing equally well, while 10% positive or 90% negative feedback informed them they were doing equally badly. In all conditions the feedback was random in relation to the listeners’ responses (because the task was to discriminate three identical tones), yet both the valence (negative vs. positive) and the probability of feedback (10% vs. 90%) affected learning. Feedback that informed listeners they were doing badly resulted in better post-training performance than feedback that informed them they were doing well, independent of valence. In addition, positive feedback during training resulted in better post-training performance than negative feedback, but only positive feedback indicating listeners were doing badly on the task resulted in learning. As we have previously speculated, feedback that better reflected the difficulty of the task was more effective in driving learning than feedback that suggested performance was better than it should have been given perceived task difficulty. But contrary to expectations, positive feedback was more effective than negative feedback in driving learning. Feedback thus had two separable effects on learning: feedback valence affected motivation on a subjectively difficult task, and learning occurred only when feedback probability reflected the subjective difficulty. To optimize learning, training programs need to take into consideration both feedback valence and probability. PMID:25946173

Removal of Negative Feedback Enhances WCST Performance for Individuals with ASD

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Broadbent, Jaclyn; Stokes, Mark A.

2013-01-01

Negative feedback was explored as a potential mechanism that may exacerbate perseverative behaviours in individuals with Asperger's syndrome (AS). The current study compared 50 individuals with AS and 50 typically developing (TD) individuals for their abilities to successfully complete the Wisconsin Card Sorting Task (WCST) in the presence or…

ttm-1 encodes CDF transporters that excrete zinc from intestinal cells of C. elegans and act in a parallel negative feedback circuit that promotes homeostasis.

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Hyun Cheol Roh

2013-05-01

Full Text Available Zinc is an essential metal involved in a wide range of biological processes, and aberrant zinc metabolism is implicated in human diseases. The gastrointestinal tract of animals is a critical site of zinc metabolism that is responsible for dietary zinc uptake and distribution to the body. However, the role of the gastrointestinal tract in zinc excretion remains unclear. Zinc transporters are key regulators of zinc metabolism that mediate the movement of zinc ions across membranes. Here, we identified a comprehensive list of 14 predicted Cation Diffusion Facilitator (CDF family zinc transporters in Caenorhabditis elegans and demonstrated that zinc is excreted from intestinal cells by one of these CDF proteins, TTM-1B. The ttm-1 locus encodes two transcripts, ttm-1a and ttm-1b, that use different transcription start sites. ttm-1b expression was induced by high levels of zinc specifically in intestinal cells, whereas ttm-1a was not induced by zinc. TTM-1B was localized to the apical plasma membrane of intestinal cells, and analyses of loss-of-function mutant animals indicated that TTM-1B promotes zinc excretion into the intestinal lumen. Zinc excretion mediated by TTM-1B contributes to zinc detoxification. These observations indicate that ttm-1 is a component of a negative feedback circuit, since high levels of cytoplasmic zinc increase ttm-1b transcript levels and TTM-1B protein functions to reduce the level of cytoplasmic zinc. We showed that TTM-1 isoforms function in tandem with CDF-2, which is also induced by high levels of cytoplasmic zinc and reduces cytoplasmic zinc levels by sequestering zinc in lysosome-related organelles. These findings define a parallel negative feedback circuit that promotes zinc homeostasis and advance the understanding of the physiological roles of the gastrointestinal tract in zinc metabolism in animals.

Feedback enhances the positive effects and reduces the negative effects of multiple-choice testing.

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Butler, Andrew C; Roediger, Henry L

2008-04-01

Multiple-choice tests are used frequently in higher education without much consideration of the impact this form of assessment has on learning. Multiple-choice testing enhances retention of the material tested (the testing effect); however, unlike other tests, multiple-choice can also be detrimental because it exposes students to misinformation in the form of lures. The selection of lures can lead students to acquire false knowledge (Roediger & Marsh, 2005). The present research investigated whether feedback could be used to boost the positive effects and reduce the negative effects of multiple-choice testing. Subjects studied passages and then received a multiple-choice test with immediate feedback, delayed feedback, or no feedback. In comparison with the no-feedback condition, both immediate and delayed feedback increased the proportion of correct responses and reduced the proportion of intrusions (i.e., lure responses from the initial multiple-choice test) on a delayed cued recall test. Educators should provide feedback when using multiple-choice tests.

Brassinosteroid-Induced Transcriptional Repression and Dephosphorylation-Dependent Protein Degradation Negatively Regulate BIN2-Interacting AIF2 (a BR Signaling-Negative Regulator) bHLH Transcription Factor.

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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.

High mobility group protein DSP1 negatively regulates HSP70 transcription in Crassostrea hongkongensis

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Miao, Zongyu; Xu, Delin; Cui, Miao; Zhang, Qizhong, E-mail: zhangqzdr@126.com

2016-06-10

HSP70 acts mostly as a molecular chaperone and plays important roles in facilitating the folding of nascent peptides as well as the refolding or degradation of the denatured proteins. Under stressed conditions, the expression level of HSP70 is upregulated significantly and rapidly, as is known to be achieved by various regulatory factors controlling the transcriptional level. In this study, a high mobility group protein DSP1 was identified by DNA-affinity purification from the nuclear extracts of Crassostrea hongkongensis using the ChHSP70 promoter as a bait. The specific interaction between the prokaryotically expressed ChDSP1 and the FITC-labeled ChHSP70 promoter was confirmed by EMSA analysis. ChDSP1 was shown to negatively regulate ChHSP70 promoter expression by Luciferase Reporter Assay in the heterologous HEK293T cells. Both ChHSP70 and ChDSP1 transcriptions were induced by either thermal or CdCl{sub 2} stress, while the accumulated expression peaks of ChDSP1 were always slightly delayed when compared with that of ChHSP70. This indicates that ChDSP1 is involved, very likely to exert its suppressive role, in the recovery of the ChHSP70 expression from the induced level to its original state. This study is the first to report negative regulator of HSP70 gene transcription, and provides novel insights into the mechanisms controlling heat shock protein expression. -- Highlights: •HMG protein ChDSP1 shows affinity to ChHSP70 promoter in Crassostrea hongkongensis. •ChDSP1 negatively regulates ChHSP70 transcription. •ChHSP70 and ChDSP1 transcriptions were coordinately induced by thermal/Cd stress. •ChDSP1 may contribute to the recovery of the induced ChHSP70 to its original state. •This is the first report regarding negative regulator of HSP70 transcription.

Advanced CANDU Design With Negative Power Feedback

International Nuclear Information System (INIS)

Andang-Widi-Harto; Muslim

2004-01-01

The problem of positive power feedback in the recent PHWR-CANDU design, especially related to coolant void increase, will be overcame by the use of dual moderator concept, in which two moderator systems are used, i.e. a main moderator outside the calandria tube and an annular moderator inside the annular space. Annular moderator is allowed to boil in the case of overheating. The numerical calculations have been performed for two core design namely HWR-DM-ST and HWR-DM-XI which can reach burn up of 16,000 and 17,500 MWd/ ton U respectively. The results for the two designs is that the values of k at fully annular moderator filling condition are 1.0054 (HWR-DM-ST) and 1.0019 (HWR-DM-XI), while at completely empty annular moderator condition are 0.9634 (HWR-DM-ST) and 0.9143 (HWR-DM-XI). The decrease of coolant flow rate from 3,043 kg/s to 853 kg/s decrease k values of 0.0109 (HWR-DM-ST) and 0.0232 (HWR-DM-XI). While increasing inlet coolant enthalpy from 2,950 kJ/kg to 3,175 kJ/kg decreases of k values of 0.0074 (HWR-DM-ST) and 0.0239 (HWR-DM-XI). Thus, it can be summarized that the HWR-DM design has negative power reactivity feedback.(author)

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

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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.

Changes in Intrinsic Motivation as a Function of Negative Feedback and Threats.

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Deci, Edward L.; Cascio, Wayne F.

Recent studies have demonstrated that external rewards can affect intrinsic motivation to perform an activity. Money tends to decrease intrinsic motivation, whereas positive verbal reinforcements tend to increase intrinsic motivation. This paper presents evidence that negative feedback and threats of punishment also decrease intrinsic motivation.…

Acute Stress Modulates Feedback Processing in Men and Women: Differential Effects on the Feedback-Related Negativity and Theta and Beta Power

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Banis, Stella; Geerligs, Linda; Lorist, Monicque M.

2014-01-01

Sex-specific prevalence rates in mental and physical disorders may be partly explained by sex differences in physiological stress responses. Neural networks that might be involved are those underlying feedback processing. Aim of the present EEG study was to investigate whether acute stress alters feedback processing, and whether stress effects differ between men and women. Male and female participants performed a gambling task, in a control and a stress condition. Stress was induced by exposing participants to a noise stressor. Brain activity was analyzed using both event-related potential and time-frequency analyses, measuring the feedback-related negativity (FRN) and feedback-related changes in theta and beta oscillatory power, respectively. While the FRN and feedback-related theta power were similarly affected by stress induction in both sexes, feedback-related beta power depended on the combination of stress induction condition and sex. FRN amplitude and theta power increases were smaller in the stress relative to the control condition in both sexes, demonstrating that acute noise stress impairs performance monitoring irrespective of sex. However, in the stress but not in the control condition, early lower beta-band power increases were larger for men than women, indicating that stress effects on feedback processing are partly sex-dependent. Our findings suggest that sex-specific effects on feedback processing may comprise a factor underlying sex-specific stress responses. PMID:24755943

Acute stress modulates feedback processing in men and women: differential effects on the feedback-related negativity and theta and beta power.

Directory of Open Access Journals (Sweden)

Stella Banis

Full Text Available Sex-specific prevalence rates in mental and physical disorders may be partly explained by sex differences in physiological stress responses. Neural networks that might be involved are those underlying feedback processing. Aim of the present EEG study was to investigate whether acute stress alters feedback processing, and whether stress effects differ between men and women. Male and female participants performed a gambling task, in a control and a stress condition. Stress was induced by exposing participants to a noise stressor. Brain activity was analyzed using both event-related potential and time-frequency analyses, measuring the feedback-related negativity (FRN and feedback-related changes in theta and beta oscillatory power, respectively. While the FRN and feedback-related theta power were similarly affected by stress induction in both sexes, feedback-related beta power depended on the combination of stress induction condition and sex. FRN amplitude and theta power increases were smaller in the stress relative to the control condition in both sexes, demonstrating that acute noise stress impairs performance monitoring irrespective of sex. However, in the stress but not in the control condition, early lower beta-band power increases were larger for men than women, indicating that stress effects on feedback processing are partly sex-dependent. Our findings suggest that sex-specific effects on feedback processing may comprise a factor underlying sex-specific stress responses.

Feedback-related negativity codes outcome valence, but not outcome expectancy, during reversal learning.

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von Borries, A K L; Verkes, R J; Bulten, B H; Cools, R; de Bruijn, E R A

2013-12-01

Optimal behavior depends on the ability to assess the predictive value of events and to adjust behavior accordingly. Outcome processing can be studied by using its electrophysiological signatures--that is, the feedback-related negativity (FRN) and the P300. A prominent reinforcement-learning model predicts an FRN on negative prediction errors, as well as implying a role for the FRN in learning and the adaptation of behavior. However, these predictions have recently been challenged. Notably, studies so far have used tasks in which the outcomes have been contingent on the response. In these paradigms, the need to adapt behavioral responses is present only for negative, not for positive feedback. The goal of the present study was to investigate the effects of positive as well as negative violations of expectancy on FRN amplitudes, without the usual confound of behavioral adjustments. A reversal-learning task was employed in which outcome value and outcome expectancy were orthogonalized; that is, both positive and negative outcomes were equally unexpected. The results revealed a double dissociation, with effects of valence but not expectancy on the FRN and, conversely, effects of expectancy but not valence on the P300. While FRN amplitudes were largest for negative-outcome trials, irrespective of outcome expectancy, P300 amplitudes were largest for unexpected-outcome trials, irrespective of outcome valence. These FRN effects were interpreted to reflect an evaluation along a good-bad dimension, rather than reflecting a negative prediction error or a role in behavioral adaptation. By contrast, the P300 reflects the updating of information relevant for behavior in a changing context.

Depression and selection of positive and negative social feedback: motivated preference or cognitive balance?

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Alloy, L B; Lipman, A J

1992-05-01

In this commentary we examine Swann, Wenzlaff, Krull, and Pelham's (1992) findings with respect to each of 5 central propositions in self-verification theory. We conclude that although the data are consistent with self-verification theory, none of the 5 components of the theory have been demonstrated convincingly as yet. Specifically, we argue that depressed subjects' selection of social feedback appears to be balanced or evenhanded rather than biased toward negative feedback and that there is little evidence to indicate that depressives actively seek negative appraisals. Furthermore, we suggest that the studies are silent with respect to the motivational postulates of self-verification theory and that a variety of competing cognitive and motivational models can explain Swann et al.'s findings as well as self-verification theory.

Self-verification and social anxiety: preference for negative social feedback and low social self-esteem.

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Valentiner, David P; Skowronski, John J; McGrath, Patrick B; Smith, Sarah A; Renner, Kerry A

2011-10-01

A self-verification model of social anxiety views negative social self-esteem as a core feature of social anxiety. This core feature is proposed to be maintained through self-verification processes, such as by leading individuals with negative social self-esteem to prefer negative social feedback. This model is tested in two studies. In Study 1, questionnaires were administered to a college sample (N = 317). In Study 2, questionnaires were administered to anxiety disordered patients (N = 62) before and after treatment. Study 1 developed measures of preference for negative social feedback and social self-esteem, and provided evidence of their incremental validity in a college sample. Study 2 found that these two variables are not strongly related to fears of evaluation, are relatively unaffected by a treatment that targets such fears, and predict residual social anxiety following treatment. Overall, these studies provide preliminary evidence for a self-verification model of social anxiety.

Cobalt ions inhibit negative feedback in the outer retina by blocking hemichannels on horizontal cells

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Fahrenfort, I.; Sjoerdsma, T.; Ripps, H.; Kamermans, M.

2004-01-01

In goldfish, negative feedback from horizontal cells to cones shifts the activation function of the Ca2+ current of the cones to more negative potentials. This shift increases the amount of Ca2+ flowing into the cones, resulting in an increase in glutamate release. The increased glutamate release

Low-backgroud preamplifier with pulse drain negative feedback

International Nuclear Information System (INIS)

Tret'yakov, V.A.; Bakhlanov, S.V.

1978-01-01

A low-noise preamplifier with a pulsed sinking negative feedback, used in an X-ray spectrometer, is described. The structural diagram of the preamplifier is presented, and its operating principle is considered. The criteria for selecting the amplitude and duration of the discharge pulse are discussed. It was established that the Usub(d) amplitude of the discharge pulse should be chosen within Usub(s) < Usub(s) < Usub(l), where Usub(s) is the voltage on the sink of the field transistor at which the avalanche production of carriers takes place, and Usub(l) is the limiting voltage at the sink; when it is exceeded, the field transistor goes into the cutoff regime. The duration of the discharge pulse should be chosen as short as possible to reduce the deadtime of the spectrometric tract. The results of an investigation into the energy resolution and the loading capacity of the spectrometer for different tau time constants of the forming filter are presented. It is shown that the energy resolution fo the spectrometer improves with increasing tau and reduces with increasing load. The use of pulsed sinkina feedback in low-noise preamplifiers to stabilize the direct-current regime makes it possible to considerably extend the loading potentialities of X-ray spectrometers

Attention training through gaze-contingent feedback: Effects on reappraisal and negative emotions.

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Sanchez, Alvaro; Everaert, Jonas; Koster, Ernst H W

2016-10-01

Reappraisal is central to emotion regulation but its mechanisms are unclear. This study tested the theoretical prediction that emotional attention bias is linked to reappraisal of negative emotion-eliciting stimuli and subsequent emotional responding using a novel attentional control training. Thirty-six undergraduates were randomly assigned to either the control or the attention training condition and were provided with different task instructions while they performed an interpretation task. Whereas control participants freely created interpretations, participants in the training condition were instructed to allocate attention toward positive words to efficiently create positive interpretations (i.e., recruiting attentional control) while they were provided with gaze-contingent feedback on their viewing behavior. Transfer to attention bias and reappraisal success was evaluated using a dot-probe task and an emotion regulation task which were administered before and after the training. The training condition was effective at increasing attentional control and resulted in beneficial effects on the transfer tasks. Analyses supported a serial indirect effect with larger attentional control acquisition in the training condition leading to negative attention bias reduction, in turn predicting greater reappraisal success which reduced negative emotions. Our results indicate that attentional mechanisms influence the use of reappraisal strategies and its impact on negative emotions. The novel attention training highlights the importance of tailored feedback to train attentional control. The findings provide an important step toward personalized delivery of attention training. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Clustering and negative feedback by endocytosis in planar cell polarity signaling is modulated by ubiquitinylation of prickle.

Directory of Open Access Journals (Sweden)

Bomsoo Cho

2015-05-01

Full Text Available The core components of the planar cell polarity (PCP signaling system, including both transmembrane and peripheral membrane associated proteins, form asymmetric complexes that bridge apical intercellular junctions. While these can assemble in either orientation, coordinated cell polarization requires the enrichment of complexes of a given orientation at specific junctions. This might occur by both positive and negative feedback between oppositely oriented complexes, and requires the peripheral membrane associated PCP components. However, the molecular mechanisms underlying feedback are not understood. We find that the E3 ubiquitin ligase complex Cullin1(Cul1/SkpA/Supernumerary limbs(Slimb regulates the stability of one of the peripheral membrane components, Prickle (Pk. Excess Pk disrupts PCP feedback and prevents asymmetry. We show that Pk participates in negative feedback by mediating internalization of PCP complexes containing the transmembrane components Van Gogh (Vang and Flamingo (Fmi, and that internalization is activated by oppositely oriented complexes within clusters. Pk also participates in positive feedback through an unknown mechanism promoting clustering. Our results therefore identify a molecular mechanism underlying generation of asymmetry in PCP signaling.

Feedback-related negativity codes outcome valence, but not outcome expectancy, during reversal learning

NARCIS (Netherlands)

Borries, A.K.L. von; Verkes, R.J.; Bulten, B.H.; Cools, R.; Bruijn, E.R.A. de

2013-01-01

Optimal behavior depends on the ability to assess the predictive value of events and to adjust behavior accordingly. Outcome processing can be studied by using its electrophysiological signatures-that is, the feedback-related negativity (FRN) and the P300. A prominent reinforcement-learning model

Feedback-related negativity codes outcome valence, but not outcome expectancy, during reversal learning

NARCIS (Netherlands)

Borries, A.K.L. von; Verkes, R.J.; Bulten, B.H.; Cools, R.

2013-01-01

Optimal behavior depends on the ability to assess the predictive value of events and to adjust behavior accordingly. Outcome processing can be studied by using its electrophysiological signatures--that is, the feedback-related negativity (FRN) and the P300. A prominent reinforcement-learning model

Examination of a perceived cost model of employees' negative feedback-seeking behavior.

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Lu, Kuo-Ming; Pan, Su-Ying; Cheng, Jen-Wei

2011-01-01

The present study extends the feedback-seeking behavior literature by investigating how supervisor-related antecedents (i.e., supervisors' expert power, reflected appraisals of supervisors, and supervisors' emotional intelligence) influence subordinates' negative feedback-seeking behavior (NFSB) through different cost/value perceptions (i.e., expectancy value, self-presentation cost, and ego cost). Using data collected from 216 supervisor-subordinate dyads from various industries in Taiwan, we employ structural equation modeling analysis to test our hypotheses. The results show that expectancy value mediates the relationship between supervisor expert power and subordinates' NFSB. Moreover, self-presentation cost mediates the relationship between reflected appraisals of supervisors' and subordinates' NFSB. Theoretical and practical implications of this study are also discussed.

Adolescents’ comments in social media: why do adolescents receive negative feedback and who is most at risk?

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Koutamanis, M.; Vossen, H.G.M.; Valkenburg, P.M.

2015-01-01

Receiving negative peer feedback in social media may have negative consequences for adolescents’ psychosocial development and well-being. Therefore, the first aim of this study was to investigate online behavior (i.e., online social exploration, risky online self-presentation) that predicts

A novel SALL4/OCT4 transcriptional feedback network for pluripotency of embryonic stem cells.

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Jianchang Yang

Full Text Available BACKGROUND: SALL4 is a member of the SALL gene family that encodes a group of putative developmental transcription factors. Murine Sall4 plays a critical role in maintaining embryonic stem cell (ES cell pluripotency and self-renewal. We have shown that Sall4 activates Oct4 and is a master regulator in murine ES cells. Other SALL gene members, especially Sall1 and Sall3 are expressed in both murine and human ES cells, and deletions of these two genes in mice lead to perinatal death due to developmental defects. To date, little is known about the molecular mechanisms controlling the regulation of expressions of SALL4 or other SALL gene family members. METHODOLOGY/PRINCIPAL FINDINGS: This report describes a novel SALL4/OCT4 regulator feedback loop in ES cells in balancing the proper expression dosage of SALL4 and OCT4 for the maintenance of ESC stem cell properties. While we have observed that a positive feedback relationship is present between SALL4 and OCT4, the strong self-repression of SALL4 seems to be the "break" for this loop. In addition, we have shown that SALL4 can repress the promoters of other SALL family members, such as SALL1 and SALL3, which competes with the activation of these two genes by OCT4. CONCLUSIONS/SIGNIFICANCE: Our findings, when taken together, indicate that SALL4 is a master regulator that controls its own expression and the expression of OCT4. SALL4 and OCT4 work antagonistically to balance the expressions of other SALL gene family members. This novel SALL4/OCT4 transcription regulation feedback loop should provide more insight into the mechanism of governing the "stemness" of ES cells.

Negative Correlation between the Diffusion Coefficient and Transcriptional Activity of the Glucocorticoid Receptor.

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Mikuni, Shintaro; Yamamoto, Johtaro; Horio, Takashi; Kinjo, Masataka

2017-08-25

The glucocorticoid receptor (GR) is a transcription factor, which interacts with DNA and other cofactors to regulate gene transcription. Binding to other partners in the cell nucleus alters the diffusion properties of GR. Raster image correlation spectroscopy (RICS) was applied to quantitatively characterize the diffusion properties of EGFP labeled human GR (EGFP-hGR) and its mutants in the cell nucleus. RICS is an image correlation technique that evaluates the spatial distribution of the diffusion coefficient as a diffusion map. Interestingly, we observed that the averaged diffusion coefficient of EGFP-hGR strongly and negatively correlated with its transcriptional activities in comparison to that of EGFP-hGR wild type and mutants with various transcriptional activities. This result suggests that the decreasing of the diffusion coefficient of hGR was reflected in the high-affinity binding to DNA. Moreover, the hyper-phosphorylation of hGR can enhance the transcriptional activity by reduction of the interaction between the hGR and the nuclear corepressors.

Adolescents' comments in social media : Why do adolescents receive negative feedback and who is most at risk?

NARCIS (Netherlands)

Koutamanis, Maria; Vossen, Helen G M; Valkenburg, Patti M.

2015-01-01

Abstract Receiving negative peer feedback in social media may have negative consequences for adolescents' psychosocial development and well-being. Therefore, the first aim of this study was to investigate online behavior (i.e., online social exploration, risky online self-presentation) that predicts

Mental models of audit and feedback in primary care settings.

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Hysong, Sylvia J; Smitham, Kristen; SoRelle, Richard; Amspoker, Amber; Hughes, Ashley M; Haidet, Paul

2018-05-30

Audit and feedback has been shown to be instrumental in improving quality of care, particularly in outpatient settings. The mental model individuals and organizations hold regarding audit and feedback can moderate its effectiveness, yet this has received limited study in the quality improvement literature. In this study we sought to uncover patterns in mental models of current feedback practices within high- and low-performing healthcare facilities. We purposively sampled 16 geographically dispersed VA hospitals based on high and low performance on a set of chronic and preventive care measures. We interviewed up to 4 personnel from each location (n = 48) to determine the facility's receptivity to audit and feedback practices. Interview transcripts were analyzed via content and framework analysis to identify emergent themes. We found high variability in the mental models of audit and feedback, which we organized into positive and negative themes. We were unable to associate mental models of audit and feedback with clinical performance due to high variance in facility performance over time. Positive mental models exhibit perceived utility of audit and feedback practices in improving performance; whereas, negative mental models did not. Results speak to the variability of mental models of feedback, highlighting how facilities perceive current audit and feedback practices. Findings are consistent with prior research  in that variability in feedback mental models is associated with lower performance.; Future research should seek to empirically link mental models revealed in this paper to high and low levels of clinical performance.

Can we bet on negative emissions to achieve the 2°C target even under strong carbon cycle feedbacks?

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Tanaka, K.; Yamagata, Y.; Yokohata, T.; Emori, S.; Hanaoka, T.

2015-12-01

Negative emission technologies such as Bioenergy with Carbon dioxide Capture and Storage (BioCCS) play an ever more crucial role in meeting the 2°C stabilization target. However, such technologies are currently at their infancy and their future penetrations may fall short of the scale required to stabilize the warming. Furthermore, the overshoot in the mid-century prior to a full realization of negative emissions would give rise to a risk because such a temporal but excessive warming above 2°C might amplify itself by strengthening climate-carbon cycle feedbacks. It has not been extensively assessed yet how carbon cycle feedbacks might play out during the overshoot in the context of negative emissions. This study explores how 2°C stabilization pathways, in particular those which undergo overshoot, can be influenced by carbon cycle feedbacks and asks their climatic and economic consequences. We compute 2°C stabilization emissions scenarios under a cost-effectiveness principle, in which the total abatement costs are minimized such that the global warming is capped at 2°C. We employ a reduced-complexity model, the Aggregated Carbon Cycle, Atmospheric Chemistry, and Climate model (ACC2), which comprises a box model of the global carbon cycle, simple parameterizations of the atmospheric chemistry, and a land-ocean energy balance model. The total abatement costs are estimated from the marginal abatement cost functions for CO2, CH4, N2O, and BC.Our preliminary results show that, if carbon cycle feedbacks turn out to be stronger than what is known today, it would incur substantial abatement costs to keep up with the 2°C stabilization goal. Our results also suggest that it would be less expensive in the long run to plan for a 2°C stabilization pathway by considering strong carbon cycle feedbacks because it would cost more if we correct the emission pathway in the mid-century to adjust for unexpectedly large carbon cycle feedbacks during overshoot. Furthermore, our

Negative derivative feedback for vibration control of flexible structures

International Nuclear Information System (INIS)

Cazzulani, G; Resta, F; Ripamonti, F; Zanzi, R

2012-01-01

In this paper a resonant control technique, called negative derivative feedback (NDF), for structural vibration control is presented. Resonant control is a class of control logics, based on the modal approach, which calculates the control action through a dynamic compensator in order to achieve a damping increase on a certain number of system modes. The NDF compensator is designed to work as a band-pass filter, cutting off the control action far from the natural frequencies associated with the controlled modes and reducing the so-called spillover effect. In the paper the proposed control logic is compared both theoretically and experimentally with the most common state-of-the-art resonant control techniques. (paper)

Negative feedback, beliefs and personal goals in prediction of dysfunctional emotions

Directory of Open Access Journals (Sweden)

Popov Boris

2007-01-01

Full Text Available Rational emotive behavior therapy (REBT demonstrates good results in evaluation therapy researches. However, some of its basic concepts, as well as theory as a whole itself, did not receive satisfactory empirical support so far, in comparison to other cognitive models (Beck, Lazarus etc.. Quasiexperimental study was designed to test the role that (1 negative feedback (A and (2 irrational beliefs (B both play in formation of dysfunctional negative emotions, in the context of significant personal goals (in our case value of potential award - G. ABC theoretical model received limited support: statistically significant three-times interaction A x B x G was found in predicting general negative emotional state, as well as anger. In contrast with that, ANOVA showed only main effect of irrational beliefs (as continuous variable to be significant in predicting emotions of anxiety and depression. Findings are discussed in the context of REBT theory of emotions, as well as their possible practical applications. Limitations of the study were also mentioned. .

Benchmark on traveling wave fast reactor with negative reactivity feedback obtained with MCNPX code

International Nuclear Information System (INIS)

Gann, V.V.; Gann, A.V.

2012-01-01

This paper presents results of computer simulations of traveling wave fast reactor with negative reactivity feedback. The results were obtained using MCNPX code combined with CINDER90 subroutine for depletion calculations. We considered 1-D model of TWR containing 4 m long core made of mixture of 66 at. % 238 U and 34 at. % 10 B. Ignitor made of 235 U was located in the center of the core. Boron was included as imitator of structural in-core materials and coolant. Negative reactivity feedback was adjusted to reactor power of 500 MW. In this case two burning waves originated from the igniter and travel to the ends of the core during the following 40 years; coefficient of utilization of 238 U reached 80 %. Distribution of specific power in traveling wave, isotope concentration of fission products and actinides, neutron flux, fast neutron spectrum, specific activity were calculated. Data of the computer simulation is in qualitative agreement with theoretical results obtained in slow burning wave approximation

Negative feedback governs gonadotrope frequency-decoding of gonadotropin releasing hormone pulse-frequency.

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Stefan Lim

Full Text Available The synthesis of the gonadotropin subunits is directed by pulsatile gonadotropin-releasing hormone (GnRH from the hypothalamus, with the frequency of GnRH pulses governing the differential expression of the common alpha-subunit, luteinizing hormone beta-subunit (LHbeta and follicle-stimulating hormone beta-subunit (FSHbeta. Three mitogen-activated protein kinases, (MAPKs, ERK1/2, JNK and p38, contribute uniquely and combinatorially to the expression of each of these subunit genes. In this study, using both experimental and computational methods, we found that dual specificity phosphatase regulation of the activity of the three MAPKs through negative feedback is required, and forms the basis for decoding the frequency of pulsatile GnRH. A fourth MAPK, ERK5, was shown also to be activated by GnRH. ERK5 was found to stimulate FSHbeta promoter activity and to increase FSHbeta mRNA levels, as well as enhancing its preference for low GnRH pulse frequencies. The latter is achieved through boosting the ultrasensitive behavior of FSHbeta gene expression by increasing the number of MAPK dependencies, and through modulating the feedforward effects of JNK activation on the GnRH receptor (GnRH-R. Our findings contribute to understanding the role of changing GnRH pulse-frequency in controlling transcription of the pituitary gonadotropins, which comprises a crucial aspect in regulating reproduction. Pulsatile stimuli and oscillating signals are integral to many biological processes, and elucidation of the mechanisms through which the pulsatility is decoded explains how the same stimulant can lead to various outcomes in a single cell.

Risky decision making from childhood through adulthood: Contributions of learning and sensitivity to negative feedback.

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Humphreys, Kathryn L; Telzer, Eva H; Flannery, Jessica; Goff, Bonnie; Gabard-Durnam, Laurel; Gee, Dylan G; Lee, Steve S; Tottenham, Nim

2016-02-01

Decision making in the context of risk is a complex and dynamic process that changes across development. Here, we assessed the influence of sensitivity to negative feedback (e.g., loss) and learning on age-related changes in risky decision making, both of which show unique developmental trajectories. In the present study, we examined risky decision making in 216 individuals, ranging in age from 3-26 years, using the balloon emotional learning task (BELT), a computerized task in which participants pump up a series of virtual balloons to earn points, but risk balloon explosion on each trial, which results in no points. It is important to note that there were 3 balloon conditions, signified by different balloon colors, ranging from quick- to slow-to-explode, and participants could learn the color-condition pairings through task experience. Overall, we found age-related increases in pumps made and points earned. However, in the quick-to-explode condition, there was a nonlinear adolescent peak for points earned. Follow-up analyses indicated that this adolescent phenotype occurred at the developmental intersection of linear age-related increases in learning and decreases in sensitivity to negative feedback. Adolescence was marked by intermediate values on both these processes. These findings show that a combination of linearly changing processes can result in nonlinear changes in risky decision making, the adolescent-specific nature of which is associated with developmental improvements in learning and reduced sensitivity to negative feedback. (c) 2016 APA, all rights reserved).

Transcription Factor Foxo1 Is a Negative Regulator of NK Cell Maturation and Function

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Deng, Youcai; Kerdiles, Yann; Chu, Jianhong; Yuan, Shunzong; Wang, Youwei; Chen, Xilin; Mao, Hsiaoyin; Zhang, Lingling; Zhang, Jianying; Hughes, Tiffany; Deng, Yafei; Zhang, Qi; Wang, Fangjie; Zou, Xianghong; Liu, Chang-Gong; Freud, Aharon G.; Li, Xiaohui; Caligiuri, Michael A; Vivier, Eric; Yu, Jianhua

2015-01-01

SUMMARY Little is known about the role of negative regulators in controlling natural killer (NK) cell development and effector functions. Foxo1 is a multifunctional transcription factor of the forkhead family. Using a mouse model of conditional deletion in NK cells, we found that Foxo1 negatively controlled NK cell differentiation and function. Immature NK cells expressed abundant Foxo1 and little Tbx21 relative to mature NK cells, but these two transcription factors reversed their expression as NK cells proceeded through development. Foxo1 promoted NK cell homing to lymph nodes through upregulating CD62L expression, and impaired late-stage maturation and effector functions by repressing Tbx21 expression. Loss of Foxo1 rescued the defect in late-stage NK cell maturation in heterozygous Tbx21+/− mice. Collectively, our data reveal a regulatory pathway by which the negative regulator Foxo1 and the positive regulator Tbx21 play opposing roles in controlling NK cell development and effector functions. PMID:25769609

Adaptive learning by extremal dynamics and negative feedback

International Nuclear Information System (INIS)

Bak, Per; Chialvo, Dante R.

2001-01-01

We describe a mechanism for biological learning and adaptation based on two simple principles: (i) Neuronal activity propagates only through the network's strongest synaptic connections (extremal dynamics), and (ii) the strengths of active synapses are reduced if mistakes are made, otherwise no changes occur (negative feedback). The balancing of those two tendencies typically shapes a synaptic landscape with configurations which are barely stable, and therefore highly flexible. This allows for swift adaptation to new situations. Recollection of past successes is achieved by punishing synapses which have once participated in activity associated with successful outputs much less than neurons that have never been successful. Despite its simplicity, the model can readily learn to solve complicated nonlinear tasks, even in the presence of noise. In particular, the learning time for the benchmark parity problem scales algebraically with the problem size N, with an exponent k∼1.4

Coupling between feedback loops in autoregulatory networks affects bistability range, open-loop gain and switching times

International Nuclear Information System (INIS)

Tiwari, Abhinav; Igoshin, Oleg A

2012-01-01

Biochemical regulatory networks governing diverse cellular processes such as stress-response, differentiation and cell cycle often contain coupled feedback loops. We aim at understanding how features of feedback architecture, such as the number of loops, the sign of the loops and the type of their coupling, affect network dynamical performance. Specifically, we investigate how bistability range, maximum open-loop gain and switching times of a network with transcriptional positive feedback are affected by additive or multiplicative coupling with another positive- or negative-feedback loop. We show that a network's bistability range is positively correlated with its maximum open-loop gain and that both quantities depend on the sign of the feedback loops and the type of feedback coupling. Moreover, we find that the addition of positive feedback could decrease the bistability range if we control the basal level in the signal-response curves of the two systems. Furthermore, the addition of negative feedback has the capacity to increase the bistability range if its dissociation constant is much lower than that of the positive feedback. We also find that the addition of a positive feedback to a bistable network increases the robustness of its bistability range, whereas the addition of a negative feedback decreases it. Finally, we show that the switching time for a transition from a high to a low steady state increases with the effective fold change in gene regulation. In summary, we show that the effect of coupled feedback loops on the bistability range and switching times depends on the underlying mechanistic details. (paper)

The Effect of Positive and Negative Feedback on Risk-Taking across Different Contexts.

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Losecaat Vermeer, Annabel B; Sanfey, Alan G

2015-01-01

Preferences for risky choices have often been shown to be unstable and context-dependent. Though people generally avoid gambles with mixed outcomes, a phenomenon often attributed to loss aversion, contextual factors can impact this dramatically. For example, people typically prefer risky options after a financial loss, while generally choosing safer options after a monetary gain. However, it is unclear what exactly contributes to these preference shifts as a function of prior outcomes, as these gain/loss outcomes are usually confounded with participant performance, and therefore it is unclear whether these effects are driven purely by the monetary gains or losses, or rather by success or failure at the actual task. Here, we experimentally separated the effects of monetary gains/losses from performance success/failure prior to a standard risky choice. Participants performed a task in which they experienced contextual effects: 1) monetary gain or loss based directly on performance, 2) monetary gain or loss that was randomly awarded and was, crucially, independent from performance, and 3) success or failure feedback based on performance, but without any monetary incentive. Immediately following these positive/negative contexts, participants were presented with a gain-loss gamble that they had to decide to either play or pass. We found that risk preferences for identical sets of gambles were biased by positive and negative contexts containing monetary gains and losses, but not by contexts containing performance feedback. This data suggests that the observed framing effects are driven by aversion for monetary losses and not simply by the positive or negative valence of the context, or by potential moods resulting from positive or negative contexts. These results highlight the specific context dependence of risk preferences.

Genome-wide binding of transcription factor ZEB1 in triple-negative breast cancer cells.

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Maturi, Varun; Enroth, Stefan; Heldin, Carl-Henrik; Moustakas, Aristidis

2018-05-10

Zinc finger E-box binding homeobox 1 (ZEB1) is a transcriptional regulator involved in embryonic development and cancer progression. ZEB1 induces epithelial-mesenchymal transition (EMT). Triple-negative human breast cancers express high ZEB1 mRNA levels and exhibit features of EMT. In the human triple-negative breast cancer cell model Hs578T, ZEB1 associates with almost 2,000 genes, representing many cellular functions, including cell polarity regulation (DLG2 and FAT3). By introducing a CRISPR-Cas9-mediated 30 bp deletion into the ZEB1 second exon, we observed reduced migratory and anchorage-independent growth capacity of these tumor cells. Transcriptomic analysis of control and ZEB1 knockout cells, revealed 1,372 differentially expressed genes. The TIMP metallopeptidase inhibitor 3 and the teneurin transmembrane protein 2 genes showed increased expression upon loss of ZEB1, possibly mediating pro-tumorigenic actions of ZEB1. This work provides a resource for regulators of cancer progression that function under the transcriptional control of ZEB1. The data confirm that removing a single EMT transcription factor, such as ZEB1, is not sufficient for reverting the triple-negative mesenchymal breast cancer cells into more differentiated, epithelial-like clones, but can reduce tumorigenic potential, suggesting that not all pro-tumorigenic actions of ZEB1 are linked to the EMT. © 2018 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

Negative-feedback control system of the high voltage power supply for ECRH

International Nuclear Information System (INIS)

Ding Tonghai; Liu Baohua; Jiang Shufang

2001-01-01

A kind of high accuracy negative high voltage power supply (HVPS) was introduced. The serial feedback was regulated according to the character of the high power tetrode and a new kind of integrator with preset value, which solved the key technological problem of the HVPS that the ECRH system required a voltage of -80 kV, a pulse width of 10 - 100 ms and a precision of 99.7%. The result using a PSPICE code simulation has shown that the method is practical

The Effect of Positive and Negative Feedback on Risk-Taking across Different Contexts.

Directory of Open Access Journals (Sweden)

Annabel B Losecaat Vermeer

Full Text Available Preferences for risky choices have often been shown to be unstable and context-dependent. Though people generally avoid gambles with mixed outcomes, a phenomenon often attributed to loss aversion, contextual factors can impact this dramatically. For example, people typically prefer risky options after a financial loss, while generally choosing safer options after a monetary gain. However, it is unclear what exactly contributes to these preference shifts as a function of prior outcomes, as these gain/loss outcomes are usually confounded with participant performance, and therefore it is unclear whether these effects are driven purely by the monetary gains or losses, or rather by success or failure at the actual task. Here, we experimentally separated the effects of monetary gains/losses from performance success/failure prior to a standard risky choice. Participants performed a task in which they experienced contextual effects: 1 monetary gain or loss based directly on performance, 2 monetary gain or loss that was randomly awarded and was, crucially, independent from performance, and 3 success or failure feedback based on performance, but without any monetary incentive. Immediately following these positive/negative contexts, participants were presented with a gain-loss gamble that they had to decide to either play or pass. We found that risk preferences for identical sets of gambles were biased by positive and negative contexts containing monetary gains and losses, but not by contexts containing performance feedback. This data suggests that the observed framing effects are driven by aversion for monetary losses and not simply by the positive or negative valence of the context, or by potential moods resulting from positive or negative contexts. These results highlight the specific context dependence of risk preferences.

TRIM45 negatively regulates NF-κB-mediated transcription and suppresses cell proliferation

International Nuclear Information System (INIS)

Shibata, Mio; Sato, Tomonobu; Nukiwa, Ryota; Ariga, Tadashi; Hatakeyama, Shigetsugu

2012-01-01

Highlights: ► NF-κB plays an important role in cell survival and carcinogenesis. ► TRIM45 negatively regulates TNFα-induced NF-κB-mediated transcription. ► TRIM45 overexpression suppresses cell growth. ► TRIM45 acts as a repressor for the NF-κB signal and regulates cell growth. -- Abstract: The NF-κB signaling pathway plays an important role in cell survival, immunity, inflammation, carcinogenesis, and organogenesis. Activation of NF-κB is regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. The NF-κB signaling pathway is activated by two distinct signaling mechanisms and is strictly modulated by the ubiquitin–proteasome system. It has been reported that overexpression of TRIM45, one of the TRIM family ubiquitin ligases, suppresses transcriptional activities of Elk-1 and AP-1, which are targets of the MAPK signaling pathway. In this study, we showed that TRIM45 also negatively regulates TNFα-induced NF-κB-mediated transcription by a luciferase reporter assay and that TRIM45 lacking a RING domain also has an activity to inhibit the NF-κB signal. Moreover, we found that TRIM45 overexpression suppresses cell growth. These findings suggest that TRIM45 acts as a repressor for the NF-κB signal and regulates cell growth.

Stability and bifurcation of numerical discretization of a second-order delay differential equation with negative feedback

International Nuclear Information System (INIS)

Ding Xiaohua; Su Huan; Liu Mingzhu

2008-01-01

The paper analyzes a discrete second-order, nonlinear delay differential equation with negative feedback. The characteristic equation of linear stability is solved, as a function of two parameters describing the strength of the feedback and the damping in the autonomous system. The existence of local Hopf bifurcations is investigated, and the direction and stability of periodic solutions bifurcating from the Hopf bifurcation of the discrete model are determined by the Hopf bifurcation theory of discrete system. Finally, some numerical simulations are performed to illustrate the analytical results found

Be kind to your eating disorder patients: the impact of positive and negative feedback on the explicit and implicit self-esteem of female patients with eating disorders.

Science.gov (United States)

Vanderlinden, J; Kamphuis, J H; Slagmolen, C; Wigboldus, D; Pieters, G; Probst, M

2009-12-01

Lack of self-esteem may play an important role in the development of eating disorders (ED). This study investigated the differential impact of positive and negative feedback on implicit and explicit self-esteem in women with an ED (N=25) as compared to women without an ED (N=29). False feedback (positive or negative) was given on participant's performance on a specifically developed intellectual test. Before and after the performance, explicit and implicit self-esteem was measured. On the explicit measure ED patients reacted congruently with the nature of the feedback. On the implicit measure only ED patients responded to the positive feedback with an improvement of self-esteem, with no effect for negative feedback. The control group was unaffected by either feedback. Furthermore, no correlation was observed between the explicit and implicit measures, a finding suggesting that these measurements tap different constructs. Positive feedback affects implicit self-esteem of female patients with eating disorders. The results underline the importance of positively approaching women with ED.

Negative feedback mechanism for the long-term stabilization of earth's surface temperature

International Nuclear Information System (INIS)

Walker, J.C.G.; Hays, P.B.; Kasting, J.F.

1981-01-01

We suggest that the partial pressure of carbon dioxide in the atmosphere is buffered, over geological time scales, by a negative feedback mechanism in which the rate of weathering of silicate minerals (followed by deposition of carbonate minerals) depends on surface temperature, and surface temperature, in turn, depends on carbon dioxide partial pressure through the green effect. Although the quantitative details of this mechanism are speculative, it appears able partially to stabilize earth's surface temperature against the steady increase of solar luminosity believed to have occured since the origin of the solar system

Using Feedback to Promote Physical Activity: The Role of the Feedback Sign.

Science.gov (United States)

Kramer, Jan-Niklas; Kowatsch, Tobias

2017-06-02

Providing feedback is a technique to promote health behavior that is emphasized by behavior change theories. However, these theories make contradicting predictions regarding the effect of the feedback sign-that is, whether the feedback signals success or failure. Thus, it is unclear whether positive or negative feedback leads to more favorable behavior change in a health behavior intervention. The aim of this study was to examine the effect of the feedback sign in a health behavior change intervention. Data from participants (N=1623) of a 6-month physical activity intervention was used. Participants received a feedback email at the beginning of each month. Feedback was either positive or negative depending on the participants' physical activity in the previous month. In an exploratory analysis, change in monthly step count averages was used to evaluate the feedback effect. The feedback sign did not predict the change in monthly step count averages over the course of the intervention (b=-84.28, P=.28). Descriptive differences between positive and negative feedback can be explained by regression to the mean. The feedback sign might not influence the effect of monthly feedback emails sent out to participants of a large-scale physical activity intervention. However, randomized studies are needed to further support this conclusion. Limitations as well as opportunities for future research are discussed. ©Jan-Niklas Kramer, Tobias Kowatsch. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 02.06.2017.

How Attributes of the Feedback Message affect Subsequent Feedback Seeking: The interactive effects of feedback sign and type

OpenAIRE

Medvedeff, Megan; Gregory, Jane Brodie; Levy, Paul E

2008-01-01

In the current study, we examined the interactive effects of feedback type and sign on feedback-seeking behaviour, as well as the moderating role of regulatory focus. Using a behavioural measure of feedback seeking, we demonstrated a strong interaction between feedback type and sign, such that individuals subsequently sought the most feedback after they were provided with negative process feedback. Additionally, results suggested that an individual's chronic regulatory focus has implications ...

A transcriptionally active estrogen receptor mutant is a novel type of dominant negative inhibitor of estrogen action.

Science.gov (United States)

McInerney, E M; Ince, B A; Shapiro, D J; Katzenellenbogen, B S

1996-12-01

We have characterized a human estrogen receptor (ER) mutant, V364E, which has a single amino acid substitution in its hormone-binding domain. This ER mutant is fully active or even superactive at saturating levels of estradiol (10(-8) M E2) yet has the capacity to act as a strong dominant negative inhibitor of the wild type ER. In transient transfection assays using ER-negative Chinese hamster ovary (CHO) cells and two different estrogen response element (ERE)-containing promoter reporter genes, V364E treated with 10(-8) M E2 exhibited approximately 250% and 100% of the activity of the wild type ER with these two promoter contexts, respectively. Despite the high activity of V364E when present alone in cells, coexpression of both V364E and wild type ER causes a significant decrease in overall ER-mediated transcriptional activity. On the TATA promoter, where V364E was more inhibitory, estrogen-stimulated activity was reduced by approximately 50% at a 1:1 ratio of mutant to wild type ER expression vector, and at a 10:1 ratio, 75% of ER activity was inhibited. V364E was expressed at lower levels than wild type ER and has a approximately 40-fold lower affinity for E2 compared with wild type ER. In promoter interference assays, V364E exhibited a strict dependence upon E2 for binding to an ERE. Surprisingly, even when V364E was unable to bind to ERE DNA (i.e. either at low E2 concentration or by mutation of its DNA-binding domain), this mutant retained full dominant negative activity. This highly active ER mutant is, thus, able to repress ER-mediated transcription when the mutant and wild type ER are present together in cells, even without DNA binding. Since competition for ERE binding and the formation of inactive heterodimers cannot fully account for the dominant negative activity of V364E, it is probable that altered interactions with proteins important in ER-mediated transcription play a key role in the repression of transcription by V364E. The properties and probable

Glucocorticoid and cytokine crosstalk: Feedback, feedforward, and co-regulatory interactions determine repression or resistance.

Science.gov (United States)

Newton, Robert; Shah, Suharsh; Altonsy, Mohammed O; Gerber, Antony N

2017-04-28

Inflammatory signals induce feedback and feedforward systems that provide temporal control. Although glucocorticoids can repress inflammatory gene expression, glucocorticoid receptor recruitment increases expression of negative feedback and feedforward regulators, including the phosphatase, DUSP1, the ubiquitin-modifying enzyme, TNFAIP3, or the mRNA-destabilizing protein, ZFP36. Moreover, glucocorticoid receptor cooperativity with factors, including nuclear factor-κB (NF-κB), may enhance regulator expression to promote repression. Conversely, MAPKs, which are inhibited by glucocorticoids, provide feedforward control to limit expression of the transcription factor IRF1, and the chemokine, CXCL10. We propose that modulation of feedback and feedforward control can determine repression or resistance of inflammatory gene expression toglucocorticoid. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Feedback and Incentives

DEFF Research Database (Denmark)

Eriksson, Tor Viking; Poulsen, Anders; Villeval, Marie Claire

2009-01-01

This paper experimentally investigates the impact of different pay schemes and relative performance feedback policies on employee effort. We explore three feedback rules: no feedback on relative performance, feedback given halfway through the production period, and continuously updated feedback. ...... behind, and front runners do not slack off. But in both pay schemes relative performance feedback reduces the quality of the low performers' work; we refer to this as a "negative quality peer effect"....

Positive and negative feedback in the earthquake cycIe: the role of pore fluids on states of criticality in the crust

Directory of Open Access Journals (Sweden)

P. R. Sammonds

1994-06-01

Full Text Available Fluids exert a strong physical and chemical control on local processes of rock fracture and friction. For example they may accelerate fracture by stress corrosion reactions or the development of overpressure (a form of positive feedback, or retard fracture by time-dependent stress relaxation or dilatant hardening (negative feed-back, thereby introducing a variable degree of local force conservation into the process. In particular the valve action of dynamic faulting may be important in tuning the Earth to a metastable state of incipient failure on all scales over several cycles, similar to current models of Self-Organised Criticality (SOC as a paradigm for eartiquakes However laboratory results suggest that ordered fluctuations about this state may occur in a single cycle due to non conservative processes involving fluids which have the potential to be recognised, at least in the short term, in the scaling properties of earthquake statistics. Here we describe a 2-D cellular automaton which uses local rules of positive and negative feedback to model the effect of fluids on failure in a heterogeneous medium in a single earthquake cycle. The model successfully predicts the observed fractal distribution of fractures, with a negative correlation between the predicted seismic b-value and the local crack extension force G. Such a negative correlation is found in laboratory tests involving (a fluid-assisted crack growth in tension (b water-saturated compressional deformation, and (c in field results on an intermediate scale from hydraulic mining-induced seismicity all cases where G can be determined independently, and where the physical and chemical action of pore fluids is to varying degrees a controlled variable. For a finite local hardening mechanism (negative feedback, the model exhibits a systematic increase followed by a decrease in the seismic b-value as macroscopic failure is approached, similar to that found in water-saturated laboratory tests

Inhibitory and toxic effects of extracellular self-DNA in litter : A mechanism for negative plant-soil feedbacks?

NARCIS (Netherlands)

Mazzoleni, Stefano; Bonanomi, Giuliano; Incerti, Guido; Chiusano, Maria Luisa; Termolino, Pasquale; Mingo, Antonio; Senatore, Mauro; Giannino, Francesco; Cartenì, Fabrizio; Rietkerk, Max; Lanzotti, Virginia

2015-01-01

Plant-soil negative feedback (NF) is recognized as an important factor affecting plant communities. The objectives of this work were to assess the effects of litter phytotoxicity and autotoxicity on root proliferation, and to test the hypothesis that DNA is a driver of litter autotoxicity and

Sparse Non-negative Matrix Factor 2-D Deconvolution for Automatic Transcription of Polyphonic Music

DEFF Research Database (Denmark)

Schmidt, Mikkel N.; Mørup, Morten

2006-01-01

We present a novel method for automatic transcription of polyphonic music based on a recently published algorithm for non-negative matrix factor 2-D deconvolution. The method works by simultaneously estimating a time-frequency model for an instrument and a pattern corresponding to the notes which...... are played based on a log-frequency spectrogram of the music....

Fetal programming: excess prenatal testosterone reduces postnatal luteinizing hormone, but not follicle-stimulating hormone responsiveness, to estradiol negative feedback in the female.

Science.gov (United States)

Sarma, Hirendra N; Manikkam, Mohan; Herkimer, Carol; Dell'Orco, James; Welch, Kathleen B; Foster, Douglas L; Padmanabhan, Vasantha

2005-10-01

Exposure of female sheep fetuses to excess testosterone (T) during early to midgestation produces postnatal hypergonadotropism manifest as a selective increase in LH. This hypergonadotropism may result from reduced sensitivity to estradiol (E2) negative feedback and/or increased pituitary sensitivity to GnRH. We tested the hypothesis that excess T before birth reduces responsiveness of LH and FSH to E2 negative feedback after birth. Pregnant ewes were treated with T propionate (100 mg/kg in cotton seed oil) or vehicle twice weekly from d 30-90 gestation. Responsiveness to E2 negative feedback was assessed at 12 and 24 wk of age in the ovary-intact female offspring. Our experimental strategy was first to arrest follicular growth and reduce endogenous E2 by administering the GnRH antagonist (GnRH-A), Nal-Glu (50 microg/kg sc every 12 h for 72 h), and then provide a fixed amount of exogenous E2 via an implant. Blood samples were obtained every 20 min at 12 wk and every 10 min at 24 wk before treatment, during and after GnRH-A treatment both before and after E2 implant. GnRH-A ablated LH pulsatility, reduced FSH by approximately 25%, and E2 production diminished to near detection limit of assay at both ages in both groups. Prenatal T treatment produced a precocious and selective reduction in responsiveness of LH but not FSH to E2 negative feedback, which was manifest mainly at the level of LH/GnRH pulse frequency. Collectively, these findings support the hypothesis that prenatal exposure to excess T decreases postnatal responsiveness to E2 inhibitory feedback of LH/GnRH secretion to contribute to the development of hypergonadotropism.

Influences of State and Trait Affect on Behavior, Feedback-Related Negativity, and P3b in the Ultimatum Game.

Directory of Open Access Journals (Sweden)

Korbinian Riepl

Full Text Available The present study investigates how different emotions can alter social bargaining behavior. An important paradigm to study social bargaining is the Ultimatum Game. There, a proposer gets a pot of money and has to offer part of it to a responder. If the responder accepts, both players get the money as proposed by the proposer. If he rejects, none of the players gets anything. Rational choice models would predict that responders accept all offers above 0. However, evidence shows that responders typically reject a large proportion of all unfair offers. We analyzed participants' behavior when they played the Ultimatum Game as responders and simultaneously collected electroencephalogram data in order to quantify the feedback-related negativity and P3b components. We induced state affect (momentarily emotions unrelated to the task via short movie clips and measured trait affect (longer-lasting emotional dispositions via questionnaires. State happiness led to increased acceptance rates of very unfair offers. Regarding neurophysiology, we found that unfair offers elicited larger feedback-related negativity amplitudes than fair offers. Additionally, an interaction of state and trait affect occurred: high trait negative affect (subsuming a variety of aversive mood states led to increased feedback-related negativity amplitudes when participants were in an angry mood, but not if they currently experienced fear or happiness. We discuss that increased rumination might be responsible for this result, which might not occur, however, when people experience happiness or fear. Apart from that, we found that fair offers elicited larger P3b components than unfair offers, which might reflect increased pleasure in response to fair offers. Moreover, high trait negative affect was associated with decreased P3b amplitudes, potentially reflecting decreased motivation to engage in activities. We discuss implications of our results in the light of theories and research on

Influences of State and Trait Affect on Behavior, Feedback-Related Negativity, and P3b in the Ultimatum Game.

Science.gov (United States)

Riepl, Korbinian; Mussel, Patrick; Osinsky, Roman; Hewig, Johannes

2016-01-01

The present study investigates how different emotions can alter social bargaining behavior. An important paradigm to study social bargaining is the Ultimatum Game. There, a proposer gets a pot of money and has to offer part of it to a responder. If the responder accepts, both players get the money as proposed by the proposer. If he rejects, none of the players gets anything. Rational choice models would predict that responders accept all offers above 0. However, evidence shows that responders typically reject a large proportion of all unfair offers. We analyzed participants' behavior when they played the Ultimatum Game as responders and simultaneously collected electroencephalogram data in order to quantify the feedback-related negativity and P3b components. We induced state affect (momentarily emotions unrelated to the task) via short movie clips and measured trait affect (longer-lasting emotional dispositions) via questionnaires. State happiness led to increased acceptance rates of very unfair offers. Regarding neurophysiology, we found that unfair offers elicited larger feedback-related negativity amplitudes than fair offers. Additionally, an interaction of state and trait affect occurred: high trait negative affect (subsuming a variety of aversive mood states) led to increased feedback-related negativity amplitudes when participants were in an angry mood, but not if they currently experienced fear or happiness. We discuss that increased rumination might be responsible for this result, which might not occur, however, when people experience happiness or fear. Apart from that, we found that fair offers elicited larger P3b components than unfair offers, which might reflect increased pleasure in response to fair offers. Moreover, high trait negative affect was associated with decreased P3b amplitudes, potentially reflecting decreased motivation to engage in activities. We discuss implications of our results in the light of theories and research on depression and

Using high-level construal and perceptions of changeability to promote self-change over self-protection motives in response to negative feedback.

Science.gov (United States)

Belding, Jennifer N; Naufel, Karen Z; Fujita, Kentaro

2015-06-01

Diagnostic negative information presents people with a motivational dilemma. Although negative feedback can provide useful information with which to guide future self-improvement efforts, it also presents short-term affective costs. We propose that construal level, jointly with the perceived changeability of the feedback domain, determines whether people choose to accept or dismiss such information. Whereas low-level construal promotes short-term self-protection motivation (promoting dismissal), high-level construal promotes long-term self-change motivation (promoting acceptance)--to the extent that change is perceived as possible. Four studies support this hypothesis and examine underlying cognitive and motivational mechanisms. The present work may provide an integrative theoretical framework for understanding when people will be open to and accept negative diagnostic information, and has important practical implications for promoting self-change efforts. © 2015 by the Society for Personality and Social Psychology, Inc.

Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

Energy Technology Data Exchange (ETDEWEB)

Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea; Furlan, Sandra; Volpe, Pompeo, E-mail: pompeo.volpe@unipd.it

2013-07-15

Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α{sub 1}-adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy.

Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

International Nuclear Information System (INIS)

Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea; Furlan, Sandra; Volpe, Pompeo

2013-01-01

Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α 1 -adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy

Elevated atmospheric CO2 negatively impacts photosynthesis through radiative forcing and physiology-mediated climate feedback

Science.gov (United States)

Zhu, Peng; Zhuang, Qianlai; Ciais, Philippe; Welp, Lisa; Li, Wenyu; Xin, Qinchuan

2017-02-01

Increasing atmospheric CO2 affects photosynthesis involving directly increasing leaf carboxylation rates, stomatal closure, and climatic effects. The direct effects are generally thought to be positive leading to increased photosynthesis, while its climatic effects can be regionally positive or negative. These effects are usually considered to be independent from each other, but they are in fact coupled through interactions between land surface exchanges of gases and heat and the physical climate system. In particular, stomatal closure reduces evapotranspiration and increases sensible heat emissions from ecosystems, leading to decreased atmospheric moisture and precipitation and local warming. We use a coupled earth system model to attribute the influence of the increase in CO2 on gross primary productivity (GPP) during the period of 1930-2011. In our model, CO2 radiative effects cause climate change that has only a negligible effect on global GPP (a reduction of 0.9 ± 2% during the last 80 years) because of opposite responses between tropical and northern biomes. On the other hand, CO2 physiological effects on GPP are both positive, by increased carboxylation rates and water use efficiency (7.1 ± 0.48% increase), and negative, by vegetation-climate feedback reducing precipitation, as a consequence of decreased transpiration and increased sensible heat in areas without water limitation (2.7 ± 1.76% reduction).When considering the coupled atmosphere-vegetation system, negative climate feedback on photosynthesis and plant growth due to the current level of CO2 opposes 29-38% of the gains from direct fertilization effects.

Negative feedback loops leading to nitrate homeostasis and oscillatory nitrate assimilation in plants and fungi.

OpenAIRE

Huang, Yongshun

2011-01-01

Master's thesis in Biological Chemistry Nitrate is an important nutrient for plants and fungi. For plants it has been shown that cytosolic nitrate levels are under homeostatic control. Here we describe two networks that can obtain robust, i.e. perturbation independent, homeostatic behavior in cytosolic nitrate concentration. One of the networks, a member in the family of outflow controllers, is based on a negative feedback loop containing a nitrate-induced activation of a controller molecu...

Fat mass and obesity associated gene (FTO expression is regulated negatively by the transcription factor Foxa2.

Directory of Open Access Journals (Sweden)

Jianjin Guo

Full Text Available Fat mass and obesity associated gene (FTO is the first gene associated with body mass index (BMI and risk for diabetes. FTO is highly expressed in the brain and pancreas, and is involved in regulating dietary intake and energy expenditure. To investigate the transcriptional regulation of FTO expression, we created 5'-deletion constructs of the FTO promoter to determine which transcription factors are most relevant to FTO expression. The presence of an activation region at -201/+34 was confirmed by luciferase activity analysis. A potential Foxa2 (called HNF-3β binding site and an upstream stimulatory factor (USF-binding site was identified in the -100 bp fragment upstream of the transcription start site (TSS. Furthermore, using mutagenesis, we identified the Foxa2 binding sequence (-26/-14 as a negative regulatory element to the activity of the human FTO promoter. The USF binding site did not affect the FTO promoter activity. Chromatin immunoprecipitation (ChIP assays were performed to confirm Foxa2 binding to the FTO promoter. Overexpression of Foxa2 in HEK 293 cells significantly down-regulated FTO promoter activity and expression. Conversely, knockdown of Foxa2 by siRNA significantly up-regulated FTO expression. These findings suggest that Foxa2 negatively regulates the basal transcription and expression of the human FTO gene.

Transcriptional network systems in cartilage development and disease.

Science.gov (United States)

Nishimura, Riko; Hata, Kenji; Nakamura, Eriko; Murakami, Tomohiko; Takahata, Yoshifumi

2018-04-01

Transcription factors play important roles in the regulation of cartilage development by controlling the expression of chondrogenic genes. Genetic studies have revealed that Sox9/Sox5/Sox6, Runx2/Runx3 and Osterix in particular are essential for the sequential steps of cartilage development. Importantly, these transcription factors form network systems that are also required for appropriate cartilage development. Molecular cloning approaches have largely contributed to the identification of several transcriptional partners for Sox9 and Runx2 during cartilage development. Although the importance of a negative-feedback loop between Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP) in chondrocyte hypertrophy has been well established, recent studies indicate that several transcription factors interact with the Ihh-PTHrP loop and demonstrated that Ihh has multiple functions in the regulation of cartilage development. The most common cartilage disorder, osteoarthritis, has been reported to result from the pathological action of several transcription factors, including Runx2, C/EBPβ and HIF-2α. On the other hand, NFAT family members appear to play roles in the protection of cartilage from osteoarthritis. It is also becoming important to understand the homeostasis and regulation of articular chondrocytes, because they have different cellular and molecular features from chondrocytes of the growth plate. This review summarizes the regulation and roles of transcriptional network systems in cartilage development and their pathological roles in osteoarthritis.

Apple (Malus domestica) MdERF2 negatively affects ethylene biosynthesis during fruit ripening by suppressing MdACS1 transcription.

Science.gov (United States)

Li, Tong; Jiang, Zhongyu; Zhang, Lichao; Tan, Dongmei; Wei, Yun; Yuan, Hui; Li, Tianlai; Wang, Aide

2016-12-01

Ripening in climacteric fruit requires the gaseous phytohormone ethylene. Although ethylene signaling has been well studied, knowledge of the transcriptional regulation of ethylene biosynthesis is still limited. Here we show that an apple (Malus domestica) ethylene response factor, MdERF2, negatively affects ethylene biosynthesis and fruit ripening by suppressing the transcription of MdACS1, a gene that is critical for biosynthesis of ripening-related ethylene. Expression of MdERF2 was suppressed by ethylene during ripening of apple fruit, and we observed that MdERF2 bound to the promoter of MdACS1 and directly suppressed its transcription. Moreover, MdERF2 suppressed the activity of the promoter of MdERF3, a transcription factor that we found to bind to the MdACS1 promoter, thereby increasing MdACS1 transcription. We determined that the MdERF2 and MdERF3 proteins directly interact, and this interaction suppresses the binding of MdERF3 to the MdACS1 promoter. Moreover, apple fruit with transiently downregulated MdERF2 expression showed higher ethylene production and faster ripening. Our results indicate that MdERF2 negatively affects ethylene biosynthesis and fruit ripening in apple by suppressing the transcription of MdACS1 via multiple mechanisms, thereby acting as an antagonist of positive ripening regulators. Our findings offer a deep understanding of the transcriptional regulation of ethylene biosynthesis during climacteric fruit ripening. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Negative Feedback Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Metamorphosis in Xenopus laevis

Science.gov (United States)

A basic understanding of the endocrinology of the hypothalamic-pituitary-thyroid (HPT) axis of anuran larvae is necessary for predicting the consequences of HPT perturbation by thyroid-disrupting chemicals (TDCs) on the whole organism. This project examined negative feedback con...

An Ocean Biology-induced Negative Feedback on ENSO in the Tropical Pacific Climate System

Science.gov (United States)

Zhang, R. H.

2016-02-01

Biological conditions in the tropical Pacific Ocean (e.g., phytoplankton biomass) are strongly regulated by physical changes associated with the El Niño-Southern Oscillation (ENSO). The existence and variation of phytoplankton biomass, in turn, act to modulate the vertical penetration of the incoming sunlight in the upper ocean, presenting an ocean biology-induced heating (OBH) effect on the climate system. Previously, a penetration depth of solar radiation in the upper ocean (Hp) is defined to describe the related bio-climate connections. Parameterized in terms of its relationship with the sea surface temperature (SST) in the tropical Pacific, an empirical model for interannual Hp variability has been derived from remotely sensed ocean color data, which is incorporated into a hybrid coupled model (HCM) to represent OBH effects. In this paper, various HCM experiments are performed to demonstrate the bio-feedback onto ENSO, including a climatological Hp run (in which Hp is prescribed as seasonally varying only), interannual Hp runs (with different intensities of interannually varying OBH effects), and a run in which the sign of the OBH effect is artificially reversed. Significant modulating impacts on interannual variability are found in the HCM, characterized by a negative feedback between ocean biology and the climate system in the tropical Pacific: the stronger the OBH feedback, the weaker the interannual variability. Processes involved in the feedback are analyzed; it is illustrated that the SST is modulated indirectly by ocean dynamical processes induced by OBH. The significance and implication of the OBH effects are discussed for their roles in ENSO variability and model biases in the tropical Pacific.

IAEA Technical Meeting on Innovative Fast Reactor Designs with Enhanced Negative Reactivity Feedback Features. Presentations

International Nuclear Information System (INIS)

2012-01-01

The objective of the TM is to review and discuss the safety characteristics and the performances of the core of innovative fast reactor concepts, as well as to present the ongoing R&D activities in the area of core design and advanced simulation tools and methods for fast reactor core physics analysis. The focus is on fast spectrum cores optimized for actinide utilization and transmutation and, in particular, on core designs with enhanced negative reactivity feedback effects

Response and binding elements for ligand-dependent positive transcription factors integrate positive and negative regulation of gene expression

International Nuclear Information System (INIS)

Rosenfeld, M.G.; Glass, C.K.; Adler, S.; Crenshaw, E.B. III; He, X.; Lira, S.A.; Elsholtz, H.P.; Mangalam, H.J.; Holloway, J.M.; Nelson, C.; Albert, V.R.; Ingraham, H.A.

1988-01-01

Accurate, regulated initiation of mRNA transcription by RNA polymerase II is dependent on the actions of a variety of positive and negative trans-acting factors that bind cis-acting promoter and enhancer elements. These transcription factors may exert their actions in a tissue-specific manner or function under control of plasma membrane or intracellular ligand-dependent receptors. A major goal in the authors' laboratory has been to identify the molecular mechanisms responsible for the serial activation of hormone-encoding genes in the pituitary during development and the positive and negative regulation of their transcription. The anterior pituitary gland contains phenotypically distinct cell types, each of which expresses unique trophic hormones: adrenocorticotropic hormone, thyroid-stimulating hormone, prolactin, growth hormone, and follicle-stimulating hormone/luteinizing hormone. The structurally related prolactin and growth hormone genes are expressed in lactotrophs and somatotrophs, respectively, with their expression virtually limited to the pituitary gland. The reported transient coexpression of these two structurally related neuroendocrine genes raises the possibility that the prolactin and growth hormone genes are developmentally controlled by a common factor(s)

An HIV feedback resistor: auto-regulatory circuit deactivator and noise buffer.

Science.gov (United States)

Weinberger, Leor S; Shenk, Thomas

2007-01-01

Animal viruses (e.g., lentiviruses and herpesviruses) use transcriptional positive feedback (i.e., transactivation) to regulate their gene expression. But positive-feedback circuits are inherently unstable when turned off, which presents a particular dilemma for latent viruses that lack transcriptional repressor motifs. Here we show that a dissipative feedback resistor, composed of enzymatic interconversion of the transactivator, converts transactivation circuits into excitable systems that generate transient pulses of expression, which decay to zero. We use HIV-1 as a model system and analyze single-cell expression kinetics to explore whether the HIV-1 transactivator of transcription (Tat) uses a resistor to shut off transactivation. The Tat feedback circuit was found to lack bi-stability and Tat self-cooperativity but exhibited a pulse of activity upon transactivation, all in agreement with the feedback resistor model. Guided by a mathematical model, biochemical and genetic perturbation of the suspected Tat feedback resistor altered the circuit's stability and reduced susceptibility to molecular noise, in agreement with model predictions. We propose that the feedback resistor is a necessary, but possibly not sufficient, condition for turning off noisy transactivation circuits lacking a repressor motif (e.g., HIV-1 Tat). Feedback resistors may be a paradigm for examining other auto-regulatory circuits and may inform upon how viral latency is established, maintained, and broken.

IAEA Technical Meeting on Innovative Fast Reactor Designs with Enhanced Negative Reactivity Feedback Features. Working Material

International Nuclear Information System (INIS)

2012-01-01

The objective of the TM was to review and discuss the safety characteristics and the performances of the core of innovative fast reactor concepts, as well as to present the ongoing R&D activities in the area of core design and advanced simulation tools and methods for fast reactor core physics analysis. The focus was on fast spectrum cores optimized for actinide utilization and transmutation and, in particular, on core designs with enhanced negative reactivity feedback effects

Combined receptor antagonist stimulation of the hypothalamic-pituitary-adrenal axis test identifies impaired negative feedback sensitivity to cortisol in obese men.

Science.gov (United States)

Mattsson, Cecilia; Reynolds, Rebecca M; Simonyte, Kotryna; Olsson, Tommy; Walker, Brian R

2009-04-01

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may underlie disorders including obesity, depression, cognitive decline, and the metabolic syndrome. Conventional tests of HPA axis negative feedback rely on glucocorticoid receptor (GR) agonists such as dexamethasone but do not test feedback by endogenous cortisol, potentially mediated by both GR and mineralocorticoid receptors (MR). The objective of the study was to use a combination of GR (RU38486, mifepristone) and MR (spironolactone) antagonists to explore the poorly understood activation of the HPA axis that occurs in obesity. This was a double-blind, placebo-controlled, randomized, crossover study. The study was conducted at a clinical research facility. Participants included 15 lean (body mass index 22.0 +/- 1.6 kg/m(2)) and 16 overweight/obese (body mass index 30.1 +/- 3.5 kg/m(2)) men. Subjects attended on four occasions for blood and saliva sampling every 30 min between 1800 and 2200 h. At 1100 and 1600 h before visits, subjects took 200 mg spironolactone, 400 mg RU38486, 200 mg spironolactone + 400 mg RU38486, or placebo orally. Serum cortisol levels after drug or placebo were measured. Cortisol levels did not differ between lean and obese after placebo. Spironolactone and RU38486 alone had modest effects, increasing cortisol by less than 50% in both groups. However, combined spironolactone plus RU38486 elevated cortisol concentrations substantially, more so in lean than obese men [2.9- (0.3) vs. 2.2 (0.3)-fold elevation, P = 0.002]. Combined receptor antagonist stimulation of the HPA axis reveals redundancy of MR and GR in negative feedback in humans. Obese men have impaired responses to combined receptor antagonist stimulation, suggesting impaired negative feedback by endogenous cortisol. Such an approach may be useful to dissect abnormal HPA axis control in neuropsychiatric and other disorders.

[Leptin and the feedback regulation of body weight].

Science.gov (United States)

Wang, X; Ye, G; Sun, J

1999-09-30

Body weight may be controlled by a negative feedback loop. Recent studies have identified that the ob gene product, leptin, apparently and exclusively expressed in adipose tissue, is a part of the negative feedback loop. Leptin is proposed to act as an afferent signal in the negative feedback loop to hypothalamus that limiting food-intake, controlling energy homeostasis and regulating the mass of adipose tissue. The dificiency of or resistance to leptin causes severe obesity.

The bantam microRNA acts through Numb to exert cell growth control and feedback regulation of Notch in tumor-forming stem cells in the Drosophila brain.

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Wu, Yen-Chi; Lee, Kyu-Sun; Song, Yan; Gehrke, Stephan; Lu, Bingwei

2017-05-01

Notch (N) signaling is central to the self-renewal of neural stem cells (NSCs) and other tissue stem cells. Its deregulation compromises tissue homeostasis and contributes to tumorigenesis and other diseases. How N regulates stem cell behavior in health and disease is not well understood. Here we show that N regulates bantam (ban) microRNA to impact cell growth, a process key to NSC maintenance and particularly relied upon by tumor-forming cancer stem cells. Notch signaling directly regulates ban expression at the transcriptional level, and ban in turn feedback regulates N activity through negative regulation of the Notch inhibitor Numb. This feedback regulatory mechanism helps maintain the robustness of N signaling activity and NSC fate. Moreover, we show that a Numb-Myc axis mediates the effects of ban on nucleolar and cellular growth independently or downstream of N. Our results highlight intricate transcriptional as well as translational control mechanisms and feedback regulation in the N signaling network, with important implications for NSC biology and cancer biology.

False feedback and beliefs influence name recall in younger and older adults.

Science.gov (United States)

Strickland-Hughes, Carla M; West, Robin Lea; Smith, Kimberly A; Ebner, Natalie C

2017-09-01

Feedback is an important self-regulatory process that affects task effort and subsequent performance. Benefits of positive feedback for list recall have been explored in research on goals and feedback, but the effect of negative feedback on memory has rarely been studied. The current research extends knowledge of memory and feedback effects by investigating face-name association memory and by examining the potential mediation of feedback effects, in younger and older adults, through self-evaluative beliefs. Beliefs were assessed before and after name recognition and name recall testing. Repeated presentation of false positive feedback was compared to false negative feedback and a no feedback condition. Results showed that memory self-efficacy declined over time for participants in the negative and no feedback conditions but was sustained for those receiving positive feedback. Furthermore, participants who received negative feedback felt older after testing than before testing. For name recall, the positive feedback group outperformed the negative feedback and no feedback groups combined, with no age interactions. The observed feedback-related effects on memory were fully mediated by changes in memory self-efficacy. These findings advance our understanding of how beliefs are related to feedback in memory and inform future studies examining the importance of self-regulation in memory.

Identification of concomitant infection with Chlamydia trachomatis IncA-negative mutant and wild-type strains by genomic, transcriptional, and biological characterizations.

Science.gov (United States)

Suchland, Robert J; Jeffrey, Brendan M; Xia, Minsheng; Bhatia, Ajay; Chu, Hencelyn G; Rockey, Daniel D; Stamm, Walter E

2008-12-01

Clinical isolates of Chlamydia trachomatis that lack IncA on their inclusion membrane form nonfusogenic inclusions and have been associated with milder, subclinical infections in patients. The molecular events associated with the generation of IncA-negative strains and their roles in chlamydial sexually transmitted infections are not clear. We explored the biology of the IncA-negative strains by analyzing their genomic structure, transcription, and growth characteristics in vitro and in vivo in comparison with IncA-positive C. trachomatis strains. Three clinical samples were identified that contained a mixture of IncA-positive and -negative same-serovar C. trachomatis populations, and two more such pairs were found in serial isolates from persistently infected individuals. Genomic sequence analysis of individual strains from each of two serovar-matched pairs showed that these pairs were very similar genetically. In contrast, the genome sequence of an unmatched IncA-negative strain contained over 5,000 nucleotide polymorphisms relative to the genome sequence of a serovar-matched but otherwise unlinked strain. Transcriptional analysis, in vitro culture kinetics, and animal modeling demonstrated that IncA-negative strains isolated in the presence of a serovar-matched wild-type strain are phenotypically more similar to the wild-type strain than are IncA-negative strains isolated in the absence of a serovar-matched wild-type strain. These studies support a model suggesting that a change from an IncA-positive strain to the previously described IncA-negative phenotype may involve multiple steps, the first of which involves a translational inactivation of incA, associated with subsequent unidentified steps that lead to the observed decrease in transcript level, differences in growth rate, and differences in mouse infectivity.

Neural correlates of anticipation and processing of performance feedback in social anxiety.

Science.gov (United States)

Heitmann, Carina Y; Peterburs, Jutta; Mothes-Lasch, Martin; Hallfarth, Marlit C; Böhme, Stephanie; Miltner, Wolfgang H R; Straube, Thomas

2014-12-01

Fear of negative evaluation, such as negative social performance feedback, is the core symptom of social anxiety. The present study investigated the neural correlates of anticipation and perception of social performance feedback in social anxiety. High (HSA) and low (LSA) socially anxious individuals were asked to give a speech on a personally relevant topic and received standardized but appropriate expert performance feedback in a succeeding experimental session in which neural activity was measured during anticipation and presentation of negative and positive performance feedback concerning the speech performance, or a neutral feedback-unrelated control condition. HSA compared to LSA subjects reported greater anxiety during anticipation of negative feedback. Functional magnetic resonance imaging results showed deactivation of medial prefrontal brain areas during anticipation of negative feedback relative to the control and the positive condition, and medial prefrontal and insular hyperactivation during presentation of negative as well as positive feedback in HSA compared to LSA subjects. The results indicate distinct processes underlying feedback processing during anticipation and presentation of feedback in HSA as compared to LSA individuals. In line with the role of the medial prefrontal cortex in self-referential information processing and the insula in interoception, social anxiety seems to be associated with lower self-monitoring during feedback anticipation, and an increased self-focus and interoception during feedback presentation, regardless of feedback valence. © 2014 Wiley Periodicals, Inc.

Feedback loop compensates for rectifier nonlinearity

Science.gov (United States)

1966-01-01

Signal processing circuit with two negative feedback loops rectifies two sinusoidal signals which are 180 degrees out of phase and produces a single full-wave rectified output signal. Each feedback loop incorporates a feedback rectifier to compensate for the nonlinearity of the circuit.

Local and global stability for Lotka-Volterra systems with distributed delays and instantaneous negative feedbacks

Science.gov (United States)

Faria, Teresa; Oliveira, José J.

This paper addresses the local and global stability of n-dimensional Lotka-Volterra systems with distributed delays and instantaneous negative feedbacks. Necessary and sufficient conditions for local stability independent of the choice of the delay functions are given, by imposing a weak nondelayed diagonal dominance which cancels the delayed competition effect. The global asymptotic stability of positive equilibria is established under conditions slightly stronger than the ones required for the linear stability. For the case of monotone interactions, however, sharper conditions are presented. This paper generalizes known results for discrete delays to systems with distributed delays. Several applications illustrate the results.

The obesity-associated transcription factor ETV5 modulates circulating glucocorticoids

Science.gov (United States)

Gutierrez-Aguilar, Ruth; Thompson, Abigail; Marchand, Nathalie; Dumont, Patrick; Woods, Stephen C.; de Launoit, Yvan; Seeley, Randy J.; Ulrich-Lai, Yvonne M.

2015-01-01

The transcription factor E-twenty-six version 5 (ETV5) has been linked with obesity in genome-wide association studies. Moreover, ETV5-deficient mice (knockout; KO) have reduced body weight, lower fat mass, and are resistant to diet-induced obesity, directly linking ETV5 to the regulation of energy balance and metabolism. ETV5 is expressed in hypothalamic brain regions that regulate both metabolism and HPA axis activity, suggesting that ETV5 may also modulate HPA axis function. In order to test this possibility, plasma corticosterone levels were measured in ETV5 KO and wildtype (WT) mice before (pre-stress) and after (post-stress) a mild stressor (intraperitoneal injection). ETV5 deficiency increased both pre- and post-stress plasma corticosterone, suggesting that loss of ETV5 elevated glucocorticoid tone. Consistent with this idea, ETV5 KO mice have reduced thymus weight, suggestive of increased glucocorticoid-induced thymic involution. ETV5 deficiency also decreased the mRNA expression of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and vasopressin receptor 1A in the hypothalamus, without altering vasopressin, corticotropin-releasing hormone, or oxytocin mRNA expression. In order to test whether reduced MR and GR expression affected glucocorticoid negative feedback, a dexamethasone suppression test was performed. Dexamethasone reduced plasma corticosterone in both ETV5 KO and WT mice, suggesting that glucocorticoid negative feedback was unaltered by ETV5 deficiency. In summary, these data suggest that the obesity-associated transcription factor ETV5 normally acts to diminish circulating glucocorticoids. This might occur directly via ETV5 actions on HPA-regulatory brain circuitry, and/or indirectly via ETV5-induced alterations in metabolic factors that then influence the HPA axis. PMID:25813907

Hvad siger forskningen om feedback?

DEFF Research Database (Denmark)

Holdt Christensen, Peter

2016-01-01

”Feedback skal serveres ligesom en gammeldags sandwich. Først lidt brød, så det lidt sejere kød og til sidst igen til lidt brød”. Sådan nogenlunde lyder en pragmatisk løsning på udfordringerne ved at give feedback. Når medarbejdere skal have negativ feedback, skal denne altså pakkes ind, så...... feedbacken indledes med let fordøjeligt positiv feedback, derefter kommer den negative – og noget sværere fordøjelige – feedback, og til sidst afrundes feedbacken med en god udgangsreplik, nemlig den positive feedback....

Social anxiety and the ironic effects of positive interviewer feedback.

Science.gov (United States)

Budnick, Christopher J; Kowal, Marta; Santuzzi, Alecia M

2015-01-01

Positive interviewer feedback should encourage positive experiences and outcomes for interviewees. Yet, positive feedback is inconsistent with socially anxious interviewees' negative self-views. Socially anxious interviewees might experience increased self-focus while attempting to reconcile the inconsistency between their self-perceptions and that feedback. This could interfere with successful interview performance. This study used a 3 (feedback: positive, negative, no) × 2 (social anxiety: high, low) between-subjects design. Undergraduate students (N = 88) completed a measure of dispositional social anxiety. They then engaged in a simulated interview with a White confederate trained to adhere to a standardized script. Interviewees received positive, negative, or no interviewer feedback. Each interview was video recorded to code anxiety displays, impression management tactics, and interview success. Following positive feedback, socially anxious interviewees displayed more anxiety, less assertiveness, and received lower success ratings. Among anxious interviewees, increased self-focus provided an indirect path between positive feedback and lower success. Consistent with self-verification theory, anxious interviewees had poorer interview performance following positive feedback that contradicted their negative self-views. Thus, socially anxious interviewees might be at a disadvantage when interviewing, especially following positive feedback. Implications for interviewees and interviewers are discussed.

A conserved SREBP-1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans.

Science.gov (United States)

Walker, Amy K; Jacobs, René L; Watts, Jennifer L; Rottiers, Veerle; Jiang, Karen; Finnegan, Deirdre M; Shioda, Toshi; Hansen, Malene; Yang, Fajun; Niebergall, Lorissa J; Vance, Dennis E; Tzoneva, Monika; Hart, Anne C; Näär, Anders M

2011-11-11

Sterol regulatory element-binding proteins (SREBPs) activate genes involved in the synthesis and trafficking of cholesterol and other lipids and are critical for maintaining lipid homeostasis. Aberrant SREBP activity, however, can contribute to obesity, fatty liver disease, and insulin resistance, hallmarks of metabolic syndrome. Our studies identify a conserved regulatory circuit in which SREBP-1 controls genes in the one-carbon cycle, which produces the methyl donor S-adenosylmethionine (SAMe). Methylation is critical for the synthesis of phosphatidylcholine (PC), a major membrane component, and we find that blocking SAMe or PC synthesis in C. elegans, mouse liver, and human cells causes elevated SREBP-1-dependent transcription and lipid droplet accumulation. Distinct from negative regulation of SREBP-2 by cholesterol, our data suggest a feedback mechanism whereby maturation of nuclear, transcriptionally active SREBP-1 is controlled by levels of PC. Thus, nutritional or genetic conditions limiting SAMe or PC production may activate SREBP-1, contributing to human metabolic disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

Stress-specific response of the p53-Mdm2 feedback loop

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Jensen Mogens H

2010-07-01

Full Text Available Abstract Background The p53 signalling pathway has hundreds of inputs and outputs. It can trigger cellular senescence, cell-cycle arrest and apoptosis in response to diverse stress conditions, including DNA damage, hypoxia and nutrient deprivation. Signals from all these inputs are channeled through a single node, the transcription factor p53. Yet, the pathway is flexible enough to produce different downstream gene expression patterns in response to different stresses. Results We construct a mathematical model of the negative feedback loop involving p53 and its inhibitor, Mdm2, at the core of this pathway, and use it to examine the effect of different stresses that trigger p53. In response to DNA damage, hypoxia, etc., the model exhibits a wide variety of specific output behaviour - steady states with low or high levels of p53 and Mdm2, as well as spiky oscillations with low or high average p53 levels. Conclusions We show that even a simple negative feedback loop is capable of exhibiting the kind of flexible stress-specific response observed in the p53 system. Further, our model provides a framework for predicting the differences in p53 response to different stresses and single nucleotide polymorphisms.

Feedback Seeking in Early Adolescence: Self-Enhancement or Self-Verification?

OpenAIRE

Rosen, Lisa H.; Principe, Connor P.; Langlois, Judith H.

2012-01-01

The authors examined whether early adolescents (N = 90) solicit self-enhancing feedback (i.e., positive feedback) or self-verifying feedback (i.e., feedback congruent with self-views, even when these views are negative). Sixth, seventh, and eighth graders first completed a self-perception measure and then selected whether to receive positive or negative feedback from an unknown peer in different domains of self. Results were consistent with self-verification theory; adolescents who perceived ...

Providing Feedback: Practical Skills and Strategies.

Science.gov (United States)

Sarkany, David; Deitte, Lori

2017-06-01

Feedback is an essential component of education. It is designed to influence, reinforce, and change behaviors, concepts, and attitudes in learners. Although providing constructive feedback can be challenging, it is a learnable skill. The negative consequences of destructive feedback or lack of feedback all together are far-reaching. This article summarizes the components of constructive feedback and provides readers with tangible skills to enhance their ability to give effective feedback to learners and peers. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Positive and negative feedback loops in nutrient phytoplankton interactions related to climate dynamics factors in a shallow temperate estuary (Vistula Lagoon, southern Baltic)

Science.gov (United States)

Kruk, Marek; Kobos, Justyna; Nawrocka, Lidia; Parszuto, Katarzyna

2018-04-01

This study aims to demonstrate that factors associated with climate dynamics, such as temperature and wind, affect the ecosystem of the shallow Vistula Lagoon in the southern Baltic and cause nutrient forms phytoplankton interactions: the growth of biomass and constraints of it. This occurs through a network of direct and indirect relationships between environmental and phytoplankton factors, including interactions of positive and negative feedback loops. Path analysis supported by structural equation modeling (SEM) was used to test hypotheses regarding the impact of climate factors on algal assemblages. Increased phytoplankton biomass was affected directly by water temperature and salinity, while the wind speed effect was indirect as it resulted in increased concentrations of suspended solids (SS) in the water column. Simultaneously, the concentration of SS in the water was positively correlated with particulate organic carbon (POC), particulate nitrogen (PN), and particulate phosphorus (PP), and was negatively correlated with the total nitrogen to phosphorus (N:P) ratio. Particulate forms of C, N, and phosphorus (P), concentrations of soluble reactive phosphorus (SRP) and nitrate and nitrite nitrogen (NO3-N + NO2-N), and ratios of the total N:P and DIN:SRP, all indirectly effected Cyanobacteria C concentrations. These processes influence other phytoplankton groups (Chlorophyta, Bacillariophyceae and the picophytoplankton fraction). Increased levels of SRP associated with organic matter (POC), which stemmed from reduced DIN:SRP ratios, contributed to increased Cyanoprokaryota and picophytoplankton C concentrations, which created a positive feedback loop. However, a simultaneous reduction in the total N:P ratio could have inhibited increases in the biomass of these assemblages by limiting N, which likely formed a negative feedback loop. The study indicates that the nutrients-phytoplankton feedback loop phenomenon can intensify eutrophication in a temperate lagoon

An Optogenetic Platform for Real-Time, Single-Cell Interrogation of Stochastic Transcriptional Regulation.

Science.gov (United States)

Rullan, Marc; Benzinger, Dirk; Schmidt, Gregor W; Milias-Argeitis, Andreas; Khammash, Mustafa

2018-05-17

Transcription is a highly regulated and inherently stochastic process. The complexity of signal transduction and gene regulation makes it challenging to analyze how the dynamic activity of transcriptional regulators affects stochastic transcription. By combining a fast-acting, photo-regulatable transcription factor with nascent RNA quantification in live cells and an experimental setup for precise spatiotemporal delivery of light inputs, we constructed a platform for the real-time, single-cell interrogation of transcription in Saccharomyces cerevisiae. We show that transcriptional activation and deactivation are fast and memoryless. By analyzing the temporal activity of individual cells, we found that transcription occurs in bursts, whose duration and timing are modulated by transcription factor activity. Using our platform, we regulated transcription via light-driven feedback loops at the single-cell level. Feedback markedly reduced cell-to-cell variability and led to qualitative differences in cellular transcriptional dynamics. Our platform establishes a flexible method for studying transcriptional dynamics in single cells. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The C'-terminal interaction domain of the thyroid hormone receptor confers the ability of the DNA site to dictate positive or negative transcriptional activity

International Nuclear Information System (INIS)

Holloway, J.M.; Glass, C.K.; Adler, S.; Nelson, C.A.; Rosenfeld, M.G.

1990-01-01

To investigate mechanisms responsible for positive and negative transcriptional control, the authors have utilized two types of promoters that are diffferentially regulated by thyroid hormone (T 3 ) receptors. Promoters containing the palindromic T 3 response element TCAGGTCA TGACCTGA are positively regulated by the T 3 receptor after the administration of T 3 , whereas otherwise identical promoters containing the estrogen response element TCAGGTCA CTG TGACCTGA can be regulated negatively; converse effects are observed with the estrogen receptor. They describe evidence that the transcriptional inhibitory effects of the T 3 or estrogen receptors on the estrogen or T 3 response elements, respectively, are imposed by amino acid sequences in the C'-terminal region that colocalize with dimerization and hormone-binding domains and that these sequences can transfer inhibitory functions to other classes of transcription factors. Removal of the C'-terminal dimerization and hormone-binding domains of either the αT 3 or estrogen receptors permits each receptor to act constitutively to enhance transcription on both T 3 and estrogen response elements. It is, therefore, suggested that protein-protein interactions between receptor C' termini limit the subset of DNA binding sites on which transcriptional activation occurs

Snf1 Phosphorylates Adenylate Cyclase and Negatively Regulates Protein Kinase A-dependent Transcription in Saccharomyces cerevisiae.

Science.gov (United States)

Nicastro, Raffaele; Tripodi, Farida; Gaggini, Marco; Castoldi, Andrea; Reghellin, Veronica; Nonnis, Simona; Tedeschi, Gabriella; Coccetti, Paola

2015-10-09

In eukaryotes, nutrient availability and metabolism are coordinated by sensing mechanisms and signaling pathways, which influence a broad set of cellular functions such as transcription and metabolic pathways to match environmental conditions. In yeast, PKA is activated in the presence of high glucose concentrations, favoring fast nutrient utilization, shutting down stress responses, and boosting growth. On the contrary, Snf1/AMPK is activated in the presence of low glucose or alternative carbon sources, thus promoting an energy saving program through transcriptional activation and phosphorylation of metabolic enzymes. The PKA and Snf1/AMPK pathways share common downstream targets. Moreover, PKA has been reported to negatively influence the activation of Snf1/AMPK. We report a new cross-talk mechanism with a Snf1-dependent regulation of the PKA pathway. We show that Snf1 and adenylate cyclase (Cyr1) interact in a nutrient-independent manner. Moreover, we identify Cyr1 as a Snf1 substrate and show that Snf1 activation state influences Cyr1 phosphorylation pattern, cAMP intracellular levels, and PKA-dependent transcription. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

A large family of antivirulence regulators modulates the effects of transcriptional activators in Gram-negative pathogenic bacteria.

Directory of Open Access Journals (Sweden)

Araceli E Santiago

2014-05-01

Full Text Available We have reported that transcription of a hypothetical small open reading frame (orf60 in enteroaggregative E. coli (EAEC strain 042 is impaired after mutation of aggR, which encodes a global virulence activator. We have also reported that the cryptic orf60 locus was linked to protection against EAEC diarrhea in two epidemiologic studies. Here, we report that the orf60 product acts as a negative regulator of aggR itself. The orf60 protein product lacks homology to known repressors, but displays 44-100% similarity to at least fifty previously undescribed small (<10 kDa hypothetical proteins found in many gram negative pathogen genomes. Expression of orf60 homologs from enterotoxigenic E. coli (ETEC repressed the expression of the AraC-transcriptional ETEC regulator CfaD/Rns and its regulon in ETEC strain H10407. Complementation in trans of EAEC 042orf60 by orf60 homologs from ETEC and the mouse pathogen Citrobacter rodentium resulted in dramatic suppression of aggR. A C. rodentium orf60 homolog mutant showed increased levels of activator RegA and increased colonization of the adult mouse. We propose the name Aar (AggR-activated regulator for the clinically and epidemiologically important orf60 product in EAEC, and postulate the existence of a large family of homologs among pathogenic Enterobacteriaceae and Pasteurellaceae. We propose the name ANR (AraC Negative Regulators for this family.

Performance feedback, self-esteem, and cardiovascular adaptation to recurring stressors.

Science.gov (United States)

Brown, Eoin G; Creaven, Ann-Marie

2017-05-01

This study sought to examine the effects of performance feedback and individual differences in self-esteem on cardiovascular habituation to repeat stress exposure. Sixty-six university students (n = 39 female) completed a self-esteem measure and completed a cardiovascular stress-testing protocol involving repeated exposure to a mental arithmetic task. Cardiovascular functioning was sampled across four phases: resting baseline, initial stress exposure, a recovery period, and repeated stress exposure. Participants were randomly assigned to receive fictional positive feedback, negative feedback, or no feedback following the recovery period. Negative feedback was associated with a sensitized blood pressure response to a second exposure of the stress task. Positive feedback was associated with decreased cardiovascular and psychological responses to a second exposure. Self-esteem was also found to predict reactivity and this interacted with the type of feedback received. These findings suggest that negative performance feedback sensitizes cardiovascular reactivity to stress, whereas positive performance feedback increases both cardiovascular and psychological habituation to repeat exposure to stressors. Furthermore, an individual's self-esteem also appears to influence this process.

Fractional dynamics of globally slow transcription and its impact on deterministic genetic oscillation.

Directory of Open Access Journals (Sweden)

Kun Wei

Full Text Available In dynamical systems theory, a system which can be described by differential equations is called a continuous dynamical system. In studies on genetic oscillation, most deterministic models at early stage are usually built on ordinary differential equations (ODE. Therefore, gene transcription which is a vital part in genetic oscillation is presupposed to be a continuous dynamical system by default. However, recent studies argued that discontinuous transcription might be more common than continuous transcription. In this paper, by appending the inserted silent interval lying between two neighboring transcriptional events to the end of the preceding event, we established that the running time for an intact transcriptional event increases and gene transcription thus shows slow dynamics. By globally replacing the original time increment for each state increment by a larger one, we introduced fractional differential equations (FDE to describe such globally slow transcription. The impact of fractionization on genetic oscillation was then studied in two early stage models--the Goodwin oscillator and the Rössler oscillator. By constructing a "dual memory" oscillator--the fractional delay Goodwin oscillator, we suggested that four general requirements for generating genetic oscillation should be revised to be negative feedback, sufficient nonlinearity, sufficient memory and proper balancing of timescale. The numerical study of the fractional Rössler oscillator implied that the globally slow transcription tends to lower the chance of a coupled or more complex nonlinear genetic oscillatory system behaving chaotically.

Fractional dynamics of globally slow transcription and its impact on deterministic genetic oscillation.

Science.gov (United States)

Wei, Kun; Gao, Shilong; Zhong, Suchuan; Ma, Hong

2012-01-01

In dynamical systems theory, a system which can be described by differential equations is called a continuous dynamical system. In studies on genetic oscillation, most deterministic models at early stage are usually built on ordinary differential equations (ODE). Therefore, gene transcription which is a vital part in genetic oscillation is presupposed to be a continuous dynamical system by default. However, recent studies argued that discontinuous transcription might be more common than continuous transcription. In this paper, by appending the inserted silent interval lying between two neighboring transcriptional events to the end of the preceding event, we established that the running time for an intact transcriptional event increases and gene transcription thus shows slow dynamics. By globally replacing the original time increment for each state increment by a larger one, we introduced fractional differential equations (FDE) to describe such globally slow transcription. The impact of fractionization on genetic oscillation was then studied in two early stage models--the Goodwin oscillator and the Rössler oscillator. By constructing a "dual memory" oscillator--the fractional delay Goodwin oscillator, we suggested that four general requirements for generating genetic oscillation should be revised to be negative feedback, sufficient nonlinearity, sufficient memory and proper balancing of timescale. The numerical study of the fractional Rössler oscillator implied that the globally slow transcription tends to lower the chance of a coupled or more complex nonlinear genetic oscillatory system behaving chaotically.

SACE_3986, a TetR family transcriptional regulator, negatively controls erythromycin biosynthesis in Saccharopolyspora erythraea.

Science.gov (United States)

Wu, Panpan; Pan, Hui; Zhang, Congming; Wu, Hang; Yuan, Li; Huang, Xunduan; Zhou, Ying; Ye, Bang-ce; Weaver, David T; Zhang, Lixin; Zhang, Buchang

2014-07-01

Erythromycin, a medically important antibiotic, is produced by Saccharopolyspora erythraea. Unusually, the erythromycin biosynthetic gene cluster lacks a regulatory gene, and the regulation of its biosynthesis remains largely unknown. In this study, through gene deletion, complementation and overexpression experiments, we identified a novel TetR family transcriptional regulator SACE_3986 negatively regulating erythromycin biosynthesis in S. erythraea A226. When SACE_3986 was further inactivated in an industrial strain WB, erythromycin A yield of the mutant was increased by 54.2 % in average compared with that of its parent strain, displaying the universality of SACE_3986 as a repressor for erythromycin production in S. erythraea. qRT-PCR analysis indicated that SACE_3986 repressed the transcription of its adjacent gene SACE_3985 (which encodes a short-chain dehydrogenase/reductase), erythromycin biosynthetic gene eryAI and the resistance gene ermE. As determined by EMSA analysis, purified SACE_3986 protein specifically bound to the intergenic region between SACE_3985 and SACE_3986, whereas it did not bind to the promoter regions of eryAI and ermE. Furthermore, overexpression of SACE_3985 in A226 led to enhanced erythromycin A yield by at least 32.6 %. These findings indicate that SACE_3986 is a negative regulator of erythromycin biosynthesis, and the adjacent gene SACE_3985 is one of its target genes. The present study provides a basis to increase erythromycin production by engineering of SACE_3986 and SACE_3985 in S. erythraea.

The Interplay between Feedback and Buffering in Cellular Homeostasis.

Science.gov (United States)

Hancock, Edward J; Ang, Jordan; Papachristodoulou, Antonis; Stan, Guy-Bart

2017-11-22

Buffering, the use of reservoirs of molecules to maintain concentrations of key molecular species, and negative feedback are the primary known mechanisms for robust homeostatic regulation. To our knowledge, however, the fundamental principles behind their combined effect have not been elucidated. Here, we study the interplay between buffering and negative feedback in the context of cellular homeostasis. We show that negative feedback counteracts slow-changing disturbances, whereas buffering counteracts fast-changing disturbances. Furthermore, feedback and buffering have limitations that create trade-offs for regulation: instability in the case of feedback and molecular noise in the case of buffering. However, because buffering stabilizes feedback and feedback attenuates noise from slower-acting buffering, their combined effect on homeostasis can be synergistic. These effects can be explained within a traditional control theory framework and are consistent with experimental observations of both ATP homeostasis and pH regulation in vivo. These principles are critical for studying robustness and homeostasis in biology and biotechnology. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A steady state analysis indicates that negative feedback regulation of PTP1B by Akt elicits bistability in insulin-stimulated GLUT4 translocation

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Giri Lopamudra

2004-08-01

Full Text Available Abstract Background The phenomenon of switch-like response to graded input signal is the theme involved in various signaling pathways in living systems. Positive feedback loops or double negative feedback loops embedded with nonlinearity exhibit these switch-like bistable responses. Such feedback regulations exist in insulin signaling pathway as well. Methods In the current manuscript, a steady state analysis of the metabolic insulin-signaling pathway is presented. The threshold concentration of insulin required for glucose transporter GLUT4 translocation was studied with variation in system parameters and component concentrations. The dose response curves of GLUT4 translocation at various concentration of insulin obtained by steady state analysis were quantified in-terms of half saturation constant. Results We show that, insulin-stimulated GLUT4 translocation can operate as a bistable switch, which ensures that GLUT4 settles between two discrete, but mutually exclusive stable steady states. The threshold concentration of insulin required for GLUT4 translocation changes with variation in system parameters and component concentrations, thus providing insights into possible pathological conditions. Conclusion A steady state analysis indicates that negative feedback regulation of phosphatase PTP1B by Akt elicits bistability in insulin-stimulated GLUT4 translocation. The threshold concentration of insulin required for GLUT4 translocation and the corresponding bistable response at different system parameters and component concentrations was compared with reported experimental observations on specific defects in regulation of the system.

Fast negative feedback enables mammalian auditory nerve fibers to encode a wide dynamic range of sound intensities.

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Mark Ospeck

Full Text Available Mammalian auditory nerve fibers (ANF are remarkable for being able to encode a 40 dB, or hundred fold, range of sound pressure levels into their firing rate. Most of the fibers are very sensitive and raise their quiescent spike rate by a small amount for a faint sound at auditory threshold. Then as the sound intensity is increased, they slowly increase their spike rate, with some fibers going up as high as ∼300 Hz. In this way mammals are able to combine sensitivity and wide dynamic range. They are also able to discern sounds embedded within background noise. ANF receive efferent feedback, which suggests that the fibers are readjusted according to the background noise in order to maximize the information content of their auditory spike trains. Inner hair cells activate currents in the unmyelinated distal dendrites of ANF where sound intensity is rate-coded into action potentials. We model this spike generator compartment as an attenuator that employs fast negative feedback. Input current induces rapid and proportional leak currents. This way ANF are able to have a linear frequency to input current (f-I curve that has a wide dynamic range. The ANF spike generator remains very sensitive to threshold currents, but efferent feedback is able to lower its gain in response to noise.

Feedback Seeking in Early Adolescence: Self-Enhancement or Self-Verification?

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Rosen, Lisa H; Principe, Connor P; Langlois, Judith H

2013-02-13

The authors examined whether early adolescents ( N = 90) solicit self-enhancing feedback (i.e., positive feedback) or self-verifying feedback (i.e., feedback congruent with self-views, even when these views are negative). Sixth, seventh, and eighth graders first completed a self-perception measure and then selected whether to receive positive or negative feedback from an unknown peer in different domains of self. Results were consistent with self-verification theory; adolescents who perceived themselves as having both strengths and weaknesses were more likely to seek negative feedback regarding a self-perceived weakness compared to a self-perceived strength. The authors found similar support for self-verification processes when they considered the entire sample regardless of perceived strengths and weaknesses; hierarchical linear modeling (HLM) examined the predictive power of ratings of self-perceived ability, certainty, and importance on feedback seeking for all participants and provided additional evidence of self-verification strivings in adolescence.

Individual Differences in the Habitual Use of Cognitive Reappraisal Predict the Reward-related Feedback Negativity

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Liyang eSai

2015-09-01

Full Text Available Recent studies have shown that instructed cognitive reappraisal can regulate the neural processing of reward. However, it is still unclear whether the habitual use of cognitive reappraisal in everyday life can influence brain activity associated with reward processing. In the present study, participant’s neural responses to reward were measured using electroencephalography (EEG recorded during a gambling task, while their tendency to use cognitive reappraisal was assessed using the Emotion Regulation Questionnaire (ERQ. Event-related potential (ERP results indicated that losses on the gambling task elicited greater negative reward-related feedback negativity (FN than gains. The differential FN between losses and gains was significantly correlated with cognitive reappraisal scores across participants, such that individuals with a higher tendency to use cognitive reappraisal showed stronger reward processing (i.e. amplified FN difference between losses and gains. This correlation remained significant after controlling for expressive suppression scores. However, expressive suppression per se was not correlated with FN differences. Taken together, these results suggest that the habitual use of cognitive reappraisal influences the neural processing of reward.

Neural Correlates of Feedback Processing in Decision Making under Risk

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Beate eSchuermann

2012-07-01

Full Text Available Introduction. Event-related brain potentials (ERP provide important information about the sensitivity of the brain to process varying risks. The aim of the present study was to determine how different risk levels are reflected in decision-related ERPs, namely the feedback-related negativity (FRN and the P300. Material and Methods. 20 participants conducted a probabilistic two-choice gambling task while an electroencephalogram was recorded. Choices were provided between a low-risk option yielding low rewards and low losses and a high-risk option yielding high rewards and high losses. While options differed in expected risks, they were equal in expected values and in feedback probabilities. Results. At the behavioral level, participants were generally risk-averse but modulated their risk-taking behavior according to reward history. An early positivity (P200 was enhanced on negative feedbacks in high-risk compared to low-risk options. With regard to the FRN, there were significant amplitude differences between positive and negative feedbacks in high-risk options, but not in low-risk options. While the FRN on negative feedbacks did not vary with decision riskiness, reduced amplitudes were found for positive feedbacks in high-risk relative to low-risk choices. P300 amplitudes were larger in high-risk decisions, and in an additive way, after negative compared to positive feedback. Discussion. The present study revealed significant influences of risk and valence processing on ERPs. FRN findings suggest that the reward prediction error signal is increased after high-risk decisions. The increased P200 on negative feedback in risky decisions suggests that large negative prediction errors are processed as early as in the P200 time range. The later P300 amplitude is sensitive to feedback valence as well as to the risk of a decision. Thus, the P300 carries additional information for reward processing, mainly the enhanced motivational significance of risky

The maize WRKY transcription factor ZmWRKY17 negatively regulates salt stress tolerance in transgenic Arabidopsis plants.

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Cai, Ronghao; Dai, Wei; Zhang, Congsheng; Wang, Yan; Wu, Min; Zhao, Yang; Ma, Qing; Xiang, Yan; Cheng, Beijiu

2017-12-01

We cloned and characterized the ZmWRKY17 gene from maize. Overexpression of ZmWRKY17 in Arabidopsis led to increased sensitivity to salt stress and decreased ABA sensitivity through regulating the expression of some ABA- and stress-responsive genes. The WRKY transcription factors have been reported to function as positive or negative regulators in many different biological processes including plant development, defense regulation and stress response. This study isolated a maize WRKY gene, ZmWRKY17, and characterized its role in tolerance to salt stress by generating transgenic Arabidopsis plants. Expression of the ZmWRKY17 was up-regulated by drought, salt and abscisic acid (ABA) treatments. ZmWRKY17 was localized in the nucleus with no transcriptional activation in yeast. Yeast one-hybrid assay showed that ZmWRKY17 can specifically bind to W-box, and it can activate W-box-dependent transcription in planta. Heterologous overexpression of ZmWRKY17 in Arabidopsis remarkably reduced plant tolerance to salt stress, as determined through physiological analyses of the cotyledons greening rate, root growth, relative electrical leakage and malondialdehyde content. Additionally, ZmWRKY17 transgenic plants showed decreased sensitivity to ABA during seed germination and early seedling growth. Transgenic plants accumulated higher content of ABA than wild-type (WT) plants under NaCl condition. Transcriptome and quantitative real-time PCR analyses revealed that some stress-related genes in transgenic seedlings showed lower expression level than that in the WT when treated with NaCl. Taken together, these results suggest that ZmWRKY17 may act as a negative regulator involved in the salt stress responses through ABA signalling.

An Actomyosin-Arf-GEF Negative Feedback Loop for Tissue Elongation under Stress.

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West, Junior J; Zulueta-Coarasa, Teresa; Maier, Janna A; Lee, Donghoon M; Bruce, Ashley E E; Fernandez-Gonzalez, Rodrigo; Harris, Tony J C

2017-08-07

In response to a pulling force, a material can elongate, hold fast, or fracture. During animal development, multi-cellular contraction of one region often stretches neighboring tissue. Such local contraction occurs by induced actomyosin activity, but molecular mechanisms are unknown for regulating the physical properties of connected tissue for elongation under stress. We show that cytohesins, and their Arf small G protein guanine nucleotide exchange activity, are required for tissues to elongate under stress during both Drosophila dorsal closure (DC) and zebrafish epiboly. In Drosophila, protein localization, laser ablation, and genetic interaction studies indicate that the cytohesin Steppke reduces tissue tension by inhibiting actomyosin activity at adherens junctions. Without Steppke, embryogenesis fails, with epidermal distortions and tears resulting from myosin misregulation. Remarkably, actomyosin network assembly is necessary and sufficient for local Steppke accumulation, where live imaging shows Steppke recruitment within minutes. This rapid negative feedback loop provides a molecular mechanism for attenuating the main tension generator of animal tissues. Such attenuation relaxes tissues and allows orderly elongation under stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

A single-repeat R3-MYB transcription factor MYBC1 negatively regulates freezing tolerance in Arabidopsis

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Zhai, Hong; Bai, Xi; Zhu, Yanming; Li, Yong; Cai, Hua; Ji, Wei; Ji, Zuojun; Liu, Xiaofei; Liu, Xin; Li, Jing

2010-01-01

We had previously identified the MYBC1 gene, which encodes a single-repeat R3-MYB protein, as a putative osmotic responding gene; however, no R3-MYB transcription factor has been reported to regulate osmotic stress tolerance. Thus, we sought to elucidate the function of MYBC1 in response to osmotic stresses. Real-time RT-PCR analysis indicated that MYBC1 expression responded to cold, dehydration, salinity and exogenous ABA at the transcript level. mybc1 mutants exhibited an increased tolerance to freezing stress, whereas 35S::MYBC1 transgenic plants exhibited decreased cold tolerance. Transcript levels of some cold-responsive genes, including CBF/DREB genes, KIN1, ADC1, ADC2 and ZAT12, though, were not altered in the mybc1 mutants or the 35S::MYBC1 transgenic plants in response to cold stress, as compared to the wild type. Microarray analysis results that are publically available were investigated and found transcript level of MYBC1 was not altered by overexpression of CBF1, CBF2, and CBF3, suggesting that MYBC1 is not down regulated by these CBF family members. Together, these results suggested that MYBC1is capable of negatively regulating the freezing tolerance of Arabidopsis in the CBF-independent pathway. In transgenic Arabidopsis carrying an MYBC1 promoter driven β-glucuronidase (GUS) construct, GUS activity was observed in all tissues and was relatively stronger in the vascular tissues. Fused MYBC1 and GFP protein revealed that MYBC1 was localized exclusively in the nuclear compartment.

Informational feedback and self-esteem among male and female athletes.

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Kamal, A F; Blais, C; McCarrey, M; Laramee, D; Ekstrand, K

1992-06-01

The self-esteem of male and female competitive athletes was compared after each was provided either positive or negative (verbal) informational feedback on a nonathletic task, a series of single-solution anagrams. Subjects were 50 men and 50 women, aged 18 to 25 years, who were tested on the semantic differential to estimate athletes' self-esteem before and after receiving the informational feedback. Over-all, female athletes responded more strongly to both feedback conditions, with both groups being more influenced by negative rather than by positive feedback.

Nonclassical state generation for linear quantum systems via nonlinear feedback control

International Nuclear Information System (INIS)

Ohki, Kentaro; Tsumura, Koji; Takeuchi, Reiji

2017-01-01

In this paper, we propose a measurement nonlinear feedback control scheme to generate Wigner-function negativity in an optical cavity having dynamics described as a linear quantum system. In general, linear optical quantum systems can be easily constructed with reliable devices; therefore, the idea of constructing the entire system with such an optical system and nonlinear feedback is reasonable for generating Wigner-function negativity. However, existing studies have insufficiently examined the realizability or actual implementation of feedback control, which essentially requires fast responses from the sensors and actuators. In order to solve this problem, we consider the realizable feedback control of the optical phase of a pumping beam supplied to a cavity by using electro-optical modulation, which can be utilized as a fast control actuator. Then, we introduce mathematical models of the feedback-controlled system and evaluate its effect on the generation of the Wigner-function negativity by using numerical simulation. Through various numerical simulations, we show that the proposed feedback control can effectively generate the negativity of the Wigner function. (paper)

Regional feedbacks under changing climate and land-use conditions

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Batlle Bayer, L.; van den Hurk, B. J. J. M.; Strengers, B. J.; van Minnen, J. G.

2012-04-01

Ecosystem responses to a changing climate and human-induced climate forcings (e.g. deforestation) might amplify (positive feedback) or dampen (negative feedback) the initial climate response. Feedbacks may include the biogeochemical (e.g. carbon cycle) and biogeophysical feedbacks (e.g. albedo and hydrological cycle). Here, we first review the most important feedbacks and put them into the context of a conceptual framework, including the major processes and interactions between terrestrial ecosystems and climate. We explore potential regional feedbacks in four hot spots with pronounced potential changes in land-use/management and local climate: sub-Saharan Africa (SSA), Europe, the Amazon Basin and South and Southeast Asia. For each region, the relevant human-induced climate forcings and feedbacks were identified based on published literature. When evapotranspiration is limited by a soil water deficit, heat waves in Europe are amplified (positive soil moisture-temperature feedback). Drought events in the Amazon lead to further rainfall reduction when water recycling processes are affected (positive soil moisture-precipitation feedback). In SSA, the adoption of irrigation in the commonly rainfed systems can modulate the negative soil moisture-temperature feedback. In contrast, future water shortage in South and Southeast Asia can turn the negative soil moisture-temperature feedback into a positive one. Further research including advanced modeling strategies is needed to isolate the dominant processes affecting the strength and sign of the feedbacks. In addition, the socio-economic dimension needs to be considered in the ecosystems-climate system to include the essential role of human decisions on land-use and land-cover change (LULCC). In this context, enhanced integration between Earth System (ES) and Integrated Assessment (IA) modeling communities is strongly recommended.

Alcohol impairs brain reactivity to explicit loss feedback.

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Nelson, Lindsay D; Patrick, Christopher J; Collins, Paul; Lang, Alan R; Bernat, Edward M

2011-11-01

Alcohol impairs the brain's detection of performance errors as evidenced by attenuated error-related negativity (ERN), an event-related potential (ERP) thought to reflect a brain system that monitors one's behavior. However, it remains unclear whether alcohol impairs performance-monitoring capacity across a broader range of contexts, including those entailing external feedback. This study sought to determine whether alcohol-related monitoring deficits are specific to internal recognition of errors (reflected by the ERN) or occur also in external cuing contexts. We evaluated the impact of alcohol consumption on the feedback-related negativity (FRN), an ERP thought to engage a similar process as the ERN but elicited by negative performance feedback in the environment. In an undergraduate sample randomly assigned to drink alcohol (n = 37; average peak BAC = 0.087 g/100 ml, estimated from breath alcohol sampling) or placebo beverages (n = 42), ERP responses to gain and loss feedback were measured during a two-choice gambling task. Time-frequency analysis was used to parse the overlapping theta-FRN and delta-P3 and clarified the effects of alcohol on the measures. Alcohol intoxication attenuated both the theta-FRN and delta-P3 brain responses to feedback. The theta-FRN attenuation was stronger following loss than gain feedback. Attenuation of both theta-FRN and delta-P3 components indicates that alcohol pervasively attenuates the brain's response to feedback in this task. That theta-FRN attenuation was stronger following loss trials is consistent with prior ERN findings and suggests that alcohol broadly impairs the brain's recognition of negative performance outcomes across differing contexts.

Unexpected Acceptance? Patients with Social Anxiety Disorder Manifest their Social Expectancy in ERPs During Social Feedback Processing

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Cao, Jianqin; Gu, Ruolei; Bi, Xuejing; Zhu, Xiangru; Wu, Haiyan

2015-01-01

Previous studies on social anxiety have demonstrated negative-expectancy bias in social contexts. In this study, we used a paradigm that employed self-relevant positive or negative social feedback, in order to test whether this negative expectancy manifests in event-related potentials (ERPs) during social evaluation among socially anxious individuals. Behavioral data revealed that individuals with social anxiety disorder (SAD) showed more negative expectancy of peer acceptance both in the experiment and in daily life than did the healthy control participants. Regarding ERP results, we found a overally larger P2 for positive social feedback and also a group main effect, such that the P2 was smaller in SAD group. SAD participants demonstrated a larger feedback-related negativity (FRN) to positive feedback than to negative feedback. In addition, SAD participants showed a more positive ΔFRN (ΔFRN = negative – positive). Furthermore, acceptance expectancy in daily life correlated negatively with ΔFRN amplitude, while the Interaction Anxiousness Scale (IAS) score correlated positively with the ΔFRN amplitude. Finally, the acceptance expectancy in daily life fully mediated the relationship between the IAS and ΔFRN. These results indicated that both groups could differentiate between positive and negative social feedback in the early stage of social feedback processing (reflected on the P2). However, the SAD group exhibited a larger FRN to positive social feedback than to negative social feedback, demonstrating their dysfunction in the late stage of social feedback processing. In our opinion, such dysfunction is due to their greater negative social feedback expectancy. PMID:26635659

Unexpected Acceptance? Patients with Social Anxiety Disorder Manifest their Social Expectancy in ERPs During Social Feedback Processing.

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Cao, Jianqin; Gu, Ruolei; Bi, Xuejing; Zhu, Xiangru; Wu, Haiyan

2015-01-01

Previous studies on social anxiety have demonstrated negative-expectancy bias in social contexts. In this study, we used a paradigm that employed self-relevant positive or negative social feedback, in order to test whether this negative expectancy manifests in event-related potentials (ERPs) during social evaluation among socially anxious individuals. Behavioral data revealed that individuals with social anxiety disorder (SAD) showed more negative expectancy of peer acceptance both in the experiment and in daily life than did the healthy control participants. Regarding ERP results, we found a overally larger P2 for positive social feedback and also a group main effect, such that the P2 was smaller in SAD group. SAD participants demonstrated a larger feedback-related negativity (FRN) to positive feedback than to negative feedback. In addition, SAD participants showed a more positive ΔFRN (ΔFRN = negative - positive). Furthermore, acceptance expectancy in daily life correlated negatively with ΔFRN amplitude, while the Interaction Anxiousness Scale (IAS) score correlated positively with the ΔFRN amplitude. Finally, the acceptance expectancy in daily life fully mediated the relationship between the IAS and ΔFRN. These results indicated that both groups could differentiate between positive and negative social feedback in the early stage of social feedback processing (reflected on the P2). However, the SAD group exhibited a larger FRN to positive social feedback than to negative social feedback, demonstrating their dysfunction in the late stage of social feedback processing. In our opinion, such dysfunction is due to their greater negative social feedback expectancy.

The CWI Pathway: Regulation of the Transcriptional Adaptive Response to Cell Wall Stress in Yeast

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Ana Belén Sanz

2017-12-01

Full Text Available Fungi are surrounded by an essential structure, the cell wall, which not only confers cell shape but also protects cells from environmental stress. As a consequence, yeast cells growing under cell wall damage conditions elicit rescue mechanisms to provide maintenance of cellular integrity and fungal survival. Through transcriptional reprogramming, yeast modulate the expression of genes important for cell wall biogenesis and remodeling, metabolism and energy generation, morphogenesis, signal transduction and stress. The yeast cell wall integrity (CWI pathway, which is very well conserved in other fungi, is the key pathway for the regulation of this adaptive response. In this review, we summarize the current knowledge of the yeast transcriptional program elicited to counterbalance cell wall stress situations, the role of the CWI pathway in the regulation of this program and the importance of the transcriptional input received by other pathways. Modulation of this adaptive response through the CWI pathway by positive and negative transcriptional feedbacks is also discussed. Since all these regulatory mechanisms are well conserved in pathogenic fungi, improving our knowledge about them will have an impact in the developing of new antifungal therapies.

Interpretation of Melanoma Risk Feedback in First-Degree Relatives of Melanoma Patients

International Nuclear Information System (INIS)

Hay, J. L.; Baguer, C.; Li, Y.; Orlow, I.; Berwick, M.

2012-01-01

Little is known about how individuals might interpret brief genetic risk feedback. We examined interpretation and behavioral intentions (sun protection, skin screening) in melanoma first-degree relatives (FDRs) after exposure to brief prototypic melanoma risk feedback. Using a 3 by 2 experimental pre-post design where feedback type (high-risk mutation, gene environment, and nongenetic) and risk level (positive versus negative findings) were systematically varied, 139 melanoma FDRs were randomized to receive one of the six scenarios. All scenarios included an explicit reminder that melanoma family history increased their risk regardless of their feedback. The findings indicate main effects by risk level but not feedback type; positive findings led to heightened anticipated melanoma risk perceptions and anticipated behavioral intentions. Yet those who received negative findings often discounted their family melanoma history. As such, 25%, 30%, and 32% of those who received negative mutation, gene-environment, and nongenetic feedback, respectively, reported that their risk was similar to the general population. Given the frequency with which those who pursue genetic testing may receive negative feedback, attention is needed to identify ideal strategies to present negative genetic findings in contexts such as direct to consumer channels where extensive genetic counseling is not required.

The developmental origins of cognitive vulnerability to depression: temperament, parenting, and negative life events in childhood as contributors to negative cognitive style.

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Mezulis, Amy H; Hyde, Janet Shibley; Abramson, Lyn Y

2006-11-01

Cognitive models of depression have been well supported with adults, but the developmental origins of cognitive vulnerability are not well understood. The authors hypothesized that temperament, parenting, and negative life events in childhood would contribute to the development of cognitive style, with withdrawal negativity and negative parental feedback moderating the effects of negative life events to predict more depressogenic cognitive styles. These constructs were assessed in 289 children and their parents followed longitudinally from infancy to 5th grade; a subsample (n = 120) also participated in a behavioral task in which maternal feedback to child failure was observed. Results indicated that greater withdrawal negativity in interaction with negative life events was associated with more negative cognitive styles. Self-reported maternal anger expression and observed negative maternal feedback to child's failure significantly interacted with child's negative events to predict greater cognitive vulnerability. There was little evidence of paternal parenting predicting child negative cognitive style.

Feedback effect on flute dynamics in a mirror machine

International Nuclear Information System (INIS)

Be’ery, I; Seemann, O

2015-01-01

The effect of active feedback on flute instability is experimentally studied in a table-top mirror machine. Changing the plasma conditions from mirror-loss dominated to flute-loss dominated, it is demonstrated that while the feedback has no effect on plasma density in the first case, it increases the plasma density by up to 50% in the second case. Measurements of the dependence of instability amplitude on feedback gain show that large gain stimulates high frequency perturbations. The period of these perturbations corresponds to the inherent delay of immersed electrode feedback. Variation of the spatial phase between the input and output of the phase reveals a large asymmetry between positive and negative phase shifts. A simplified model is introduced to explain how a negative phase shift causes positive feedback between the external feedback and the centrifugally driven rotation. (paper)

The Mycobacterium tuberculosis transcriptional repressor EthR is negatively regulated by Serine/Threonine phosphorylation.

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Leiba, Jade; Carrère-Kremer, Séverine; Blondiaux, Nicolas; Dimala, Martin Moune; Wohlkönig, Alexandre; Baulard, Alain; Kremer, Laurent; Molle, Virginie

2014-04-18

Recent efforts have underlined the role of Serine/Threonine Protein Kinases (STPKs) in growth, pathogenesis and cell wall metabolism in mycobacteria. Herein, we demonstrated that the Mycobacterium tuberculosis EthR, a transcriptional repressor that regulates the activation process of the antitubercular drug ethionamide (ETH) is a specific substrate of the mycobacterial kinase PknF. ETH is a prodrug that must undergo bioactivation by the monooxygenease EthA to exert its antimycobacterial activity and previous studies reported that EthR represses transcription of ethA by binding to the ethA-ethR intergenic region. Mass spectrometry analyses and site-directed mutagenesis identified a set of four phosphoacceptors, namely Thr2, Thr3, Ser4 and Ser7. This was further supported by the complete loss of PknF-dependent phosphorylation of a phosphoablative EthR mutant protein. Importantly, a phosphomimetic version of EthR, in which all phosphosites were replaced by Asp residues, exhibited markedly decreased DNA-binding activity compared with the wild-type protein. Together, these findings are the first demonstration of EthR phosphorylation and indicate that phosphorylation negatively affects its DNA-binding activity, which may impact ETH resistance levels in M. tb. Copyright © 2014 Elsevier Inc. All rights reserved.

Self-esteem, performance feedback, and cardiovascular stress reactivity.

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Hughes, Brian M

2007-09-01

This study sought to establish the impact of performance-related feedback on cardiovascular responses to stressors, and whether this impact is influenced by individual differences in self-esteem. A total of 66 college women were categorized as either high or low in self-esteem on the basis of their scores in a standardized psychometric test. They then took part in a laboratory experiment, in which they were assigned to one of three performance-feedback manipulations. Following the provision of feedback on an initial laboratory task (picture-matching), they undertook a second task (mental arithmetic). Cardiovascular functioning was monitored throughout. Provision of negative feedback to the initial task exerted an adverse impact on cardiovascular responses, suggestive of unhappiness with performance. Provision of positive feedback to the initial task exerted an impact on cardiovascular functioning during the second task, suggestive of task engagement. Importantly, low self-esteem exacerbated the adverse impact of negative feedback. The impact of feedback and the buffering role of self-esteem may have important consequences for cardiovascular health. Further, discrepancies in the findings of previous feedback research may be accounted for by dispositional individual differences.

Smart conjugated polymer nanocarrier for healthy weight loss by negative feedback regulation of lipase activity

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Chen, Yu-Lei; Zhu, Sha; Zhang, Lei; Feng, Pei-Jian; Yao, Xi-Kuang; Qian, Cheng-Gen; Zhang, Can; Jiang, Xi-Qun; Shen, Qun-Dong

2016-02-01

Healthy weight loss represents a real challenge when obesity is increasing in prevalence. Herein, we report a conjugated polymer nanocarrier for smart deactivation of lipase and thus balancing calorie intake. After oral administration, the nanocarrier is sensitive to lipase in the digestive tract and releases orlistat, which deactivates the enzyme and inhibits fat digestion. It also creates negative feedback to control the release of itself. The nanocarrier smartly regulates activity of the lipase cyclically varied between high and low levels. In spite of high fat diet intervention, obese mice receiving a single dose of the nanocarrier lose weight over eight days, whereas a control group continues the tendency to gain weight. Daily intragastric administration of the nanocarrier leads to lower weight of livers or fat pads, smaller adipocyte size, and lower total cholesterol level than that of the control group. Near-infrared fluorescence of the nanocarrier reveals its biodistribution.Healthy weight loss represents a real challenge when obesity is increasing in prevalence. Herein, we report a conjugated polymer nanocarrier for smart deactivation of lipase and thus balancing calorie intake. After oral administration, the nanocarrier is sensitive to lipase in the digestive tract and releases orlistat, which deactivates the enzyme and inhibits fat digestion. It also creates negative feedback to control the release of itself. The nanocarrier smartly regulates activity of the lipase cyclically varied between high and low levels. In spite of high fat diet intervention, obese mice receiving a single dose of the nanocarrier lose weight over eight days, whereas a control group continues the tendency to gain weight. Daily intragastric administration of the nanocarrier leads to lower weight of livers or fat pads, smaller adipocyte size, and lower total cholesterol level than that of the control group. Near-infrared fluorescence of the nanocarrier reveals its biodistribution

Cardiac Concomitants of Feedback and Prediction Error Processing in Reinforcement Learning

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Kastner, Lucas; Kube, Jana; Villringer, Arno; Neumann, Jane

2017-01-01

Successful learning hinges on the evaluation of positive and negative feedback. We assessed differential learning from reward and punishment in a monetary reinforcement learning paradigm, together with cardiac concomitants of positive and negative feedback processing. On the behavioral level, learning from reward resulted in more advantageous behavior than learning from punishment, suggesting a differential impact of reward and punishment on successful feedback-based learning. On the autonomic level, learning and feedback processing were closely mirrored by phasic cardiac responses on a trial-by-trial basis: (1) Negative feedback was accompanied by faster and prolonged heart rate deceleration compared to positive feedback. (2) Cardiac responses shifted from feedback presentation at the beginning of learning to stimulus presentation later on. (3) Most importantly, the strength of phasic cardiac responses to the presentation of feedback correlated with the strength of prediction error signals that alert the learner to the necessity for behavioral adaptation. Considering participants' weight status and gender revealed obesity-related deficits in learning to avoid negative consequences and less consistent behavioral adaptation in women compared to men. In sum, our results provide strong new evidence for the notion that during learning phasic cardiac responses reflect an internal value and feedback monitoring system that is sensitive to the violation of performance-based expectations. Moreover, inter-individual differences in weight status and gender may affect both behavioral and autonomic responses in reinforcement-based learning. PMID:29163004

Cardiac Concomitants of Feedback and Prediction Error Processing in Reinforcement Learning

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Lucas Kastner

2017-10-01

Full Text Available Successful learning hinges on the evaluation of positive and negative feedback. We assessed differential learning from reward and punishment in a monetary reinforcement learning paradigm, together with cardiac concomitants of positive and negative feedback processing. On the behavioral level, learning from reward resulted in more advantageous behavior than learning from punishment, suggesting a differential impact of reward and punishment on successful feedback-based learning. On the autonomic level, learning and feedback processing were closely mirrored by phasic cardiac responses on a trial-by-trial basis: (1 Negative feedback was accompanied by faster and prolonged heart rate deceleration compared to positive feedback. (2 Cardiac responses shifted from feedback presentation at the beginning of learning to stimulus presentation later on. (3 Most importantly, the strength of phasic cardiac responses to the presentation of feedback correlated with the strength of prediction error signals that alert the learner to the necessity for behavioral adaptation. Considering participants' weight status and gender revealed obesity-related deficits in learning to avoid negative consequences and less consistent behavioral adaptation in women compared to men. In sum, our results provide strong new evidence for the notion that during learning phasic cardiac responses reflect an internal value and feedback monitoring system that is sensitive to the violation of performance-based expectations. Moreover, inter-individual differences in weight status and gender may affect both behavioral and autonomic responses in reinforcement-based learning.

A feedback regulatory model for RifQ-mediated repression of rifamycin export in Amycolatopsis mediterranei.

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Lei, Chao; Wang, Jingzhi; Liu, Yuanyuan; Liu, Xinqiang; Zhao, Guoping; Wang, Jin

2018-01-29

Due to the important role of rifamycin in curing tuberculosis infection, the study on rifamycin has never been stopped. Although RifZ, which locates within the rifamycin biosynthetic cluster, has recently been characterized as a pathway-specific regulator for rifamycin biosynthesis, little is known about the regulation of rifamycin export. In this work, we proved that the expression of the rifamycin efflux pump (RifP) was regulated by RifQ, a TetR-family transcriptional regulator. Deletion of rifQ had little impact on bacterial growth, but resulted in improved rifamycin production, which was consistent with the reverse transcription PCR results that RifQ negatively regulated rifP's transcription. With electrophoretic mobility shift assay and DNase I Footprinting assay, RifQ was found to directly bind to the promoter region of rifP, and a typical inverted repeat was identified within the RifQ-protected sequences. The transcription initiation site of rifP was further characterized and found to be upstream of the RifQ binding sites, well explaining the RifQ-mediated repression of rifP's transcription in vivo. Moreover, rifamycin B (the end product of rifamycin biosynthesis) remarkably decreased the DNA binding affinity of RifQ, which led to derepression of rifamycin export, reducing the intracellular concentration of rifamycin B as well as its toxicity against the host. Here, we proved that the export of rifamycin B was repressed by RifQ in Amycolatopsis mediterranei, and the RifQ-mediated repression could be specifically relieved by rifamycin B, the end product of rifamycin biosynthesis, based on which a feedback model was proposed for regulation of rifamycin export. With the findings here, one could improve the antibiotic yield by simply inactivating the negative regulator of the antibiotic transporter.

Cloud-radiation interactions - Effects of cirrus optical thickness feedbacks

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Somerville, Richard C. J.; Iacobellis, Sam

1987-01-01

The paper is concerned with a cloud-radiation feedback mechanism which may be an important component of the climate changes expected from increased atmospheric concentrations of carbon dioxide and other trace greenhouse gases. A major result of the study is that cirrus cloud optical thickness feedbacks may indeed tend to increase the surface warming due to trace gas increases. However, the positive feedback from cirrus appears to be generally weaker than the negative effects due to lower clouds. The results just confirm those of earlier research indicating that the net effect of cloud optical thickness feedbacks may be a negative feedback which may substantially (by a factor of about 2) reduce the surface warming due to the doubling of CO2, even in the presence of cirrus clouds.

Unexpected acceptance? Patients with social anxiety disorder manifest their social expectancy in ERPs during social feedback processing

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Jianqin eCao

2015-11-01

Full Text Available Previous studies on social anxiety have demonstrated negative-expectancy bias in social contexts. In this study, we used a paradigm that employed self-relevant positive or negative social feedback, in order to test whether this negative expectancy manifests in event-related potentials (ERPs during social evaluation among socially anxious individuals. Behavioral data revealed that individuals with social anxiety disorder (SAD showed more negative expectancy of peer acceptance both in the experiment and in daily life than did the healthy control (HC participants. Regarding ERP results, we found a overally larger P2 for positive social feedback and also a group main effect, such that the P2 was smaller in SAD group. SAD participants demonstrated a larger FRN to positive feedback than to negative feedback. In addition, SAD participants showed a more positive △FRN (△FRN = negative - positive. Furthermore, acceptance expectancy in daily life correlated negatively with △FRN amplitude, while the Interaction Anxiousness Scale (IAS score correlated positively with the △FRN amplitude. Finally, the acceptance expectancy in daily life fully mediated the relationship between the IAS and △FRN. These results indicated that both groups could differentiate between positive and negative social feedback in the early stage of social feedback processing (reflected on the P2. However, the SAD group exhibited a larger FRN to positive social feedback than to negative social feedback, demonstrating their dysfunction in the late stage of social feedback processing. In our opinion, such dysfunction is due to their greater negative social feedback expectancy.

Osteoclasts and CD8 T cells form a negative feedback loop that contributes to homeostasis of both the skeletal and immune systems.

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Buchwald, Zachary S; Aurora, Rajeev

2013-01-01

There are a number of dynamic regulatory loops that maintain homeostasis of the immune and skeletal systems. In this review, we highlight a number of these regulatory interactions that contribute to maintaining homeostasis. In addition, we review data on a negative regulatory feedback loop between osteoclasts and CD8 T cells that contributes to homeostasis of both the skeletal and immune systems.

A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity.

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Kateřina Cetkovská

Full Text Available Williams-Beuren syndrome-associated transcription factor TFII-I plays a critical regulatory role in bone and neural tissue development and in immunity, in part by regulating cell proliferation in response to mitogens. Mdm2, a cellular oncogene responsible for the loss of p53 tumor suppressor activity in a significant proportion of human cancers, was identified in this study as a new binding partner for TFII-I and a negative regulator of TFII-I-mediated transcription. These findings suggest a new p53-independent mechanism by which increased Mdm2 levels found in human tumors could influence cancer cells. In addition to that, we present data indicating that TFII-I is an important cellular regulator of transcription from the immediate-early promoter of human cytomegalovirus, a promoter sequence frequently used in mammalian expression vectors, including vectors for gene therapy. Our observation that Mdm2 over-expression can decrease the ability of TFII-I to activate the CMV promoter might have implications for the efficiency of experimental gene therapy based on CMV promoter-derived vectors in cancers with Mdm2 gene amplification.

Enhancing Feedback on Professionalism and Communication Skills in Anesthesia Residency Programs.

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Mitchell, John D; Ku, Cindy; Diachun, Carol Ann B; DiLorenzo, Amy; Lee, Daniel E; Karan, Suzanne; Wong, Vanessa; Schell, Randall M; Brzezinski, Marek; Jones, Stephanie B

2017-08-01

Despite its importance, training faculty to provide feedback to residents remains challenging. We hypothesized that, overall, at 4 institutions, a faculty development program on providing feedback on professionalism and communication skills would lead to (1) an improvement in the quantity, quality, and utility of feedback and (2) an increase in feedback containing negative/constructive feedback and pertaining to professionalism/communication. As secondary analyses, we explored these outcomes at the individual institutions. In this prospective cohort study (October 2013 to July 2014), we implemented a video-based educational program on feedback at 4 institutions. Feedback records from 3 months before to 3 months after the intervention were rated for quality (0-5), utility (0-5), and whether they had negative/constructive feedback and/or were related to professionalism/communication. Feedback records during the preintervention, intervention, and postintervention periods were compared using the Kruskal-Wallis and χ tests. Data are reported as median (interquartile range) or proportion/percentage. A total of 1926 feedback records were rated. The institutions overall did not have a significant difference in feedback quantity (preintervention: 855/3046 [28.1%]; postintervention: 896/3327 [26.9%]; odds ratio: 1.06; 95% confidence interval, 0.95-1.18; P = .31), feedback quality (preintervention: 2 [1-4]; intervention: 2 [1-4]; postintervention: 2 [1-4]; P = .90), feedback utility (preintervention: 1 [1-3]; intervention: 2 [1-3]; postintervention: 1 [1-2]; P = .61), or percentage of feedback records containing negative/constructive feedback (preintervention: 27%; intervention: 32%; postintervention: 25%; P = .12) or related to professionalism/communication (preintervention: 23%; intervention: 33%; postintervention: 24%; P = .03). Institution 1 had a significant difference in feedback quality (preintervention: 2 [1-3]; intervention: 3 [2-4]; postintervention: 3 [2-4]; P

Feedback Seeking in Early Adolescence: Self-Enhancement or Self-Verification?

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Rosen, Lisa H.; Principe, Connor P.; Langlois, Judith H.

2013-01-01

The authors examined whether early adolescents ("N" = 90) solicit self-enhancing feedback (i.e., positive feedback) or self-verifying feedback (i.e., feedback congruent with self-views, even when these views are negative). Sixth, seventh, and eighth graders first completed a self-perception measure and then selected whether to receive…

Performance Feedback Processing Is Positively Biased As Predicted by Attribution Theory.

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Christoph W Korn

Full Text Available A considerable literature on attribution theory has shown that healthy individuals exhibit a positivity bias when inferring the causes of evaluative feedback on their performance. They tend to attribute positive feedback internally (e.g., to their own abilities but negative feedback externally (e.g., to environmental factors. However, all empirical demonstrations of this bias suffer from at least one of the three following drawbacks: First, participants directly judge explicit causes for their performance. Second, participants have to imagine events instead of experiencing them. Third, participants assess their performance only after receiving feedback and thus differences in baseline assessments cannot be excluded. It is therefore unclear whether the classically reported positivity bias generalizes to setups without these drawbacks. Here, we aimed at establishing the relevance of attributions for decision-making by showing an attribution-related positivity bias in a decision-making task. We developed a novel task, which allowed us to test how participants changed their evaluations in response to positive and negative feedback about performance. Specifically, we used videos of actors expressing different facial emotional expressions. Participants were first asked to evaluate the actors' credibility in expressing a particular emotion. After this initial rating, participants performed an emotion recognition task and did--or did not--receive feedback on their veridical performance. Finally, participants re-rated the actors' credibility, which provided a measure of how they changed their evaluations after feedback. Attribution theory predicts that participants change their evaluations of the actors' credibility toward the positive after receiving positive performance feedback and toward the negative after negative performance feedback. Our results were in line with this prediction. A control condition without feedback showed that correct or

Performance Feedback Processing Is Positively Biased As Predicted by Attribution Theory.

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Korn, Christoph W; Rosenblau, Gabriela; Rodriguez Buritica, Julia M; Heekeren, Hauke R

2016-01-01

A considerable literature on attribution theory has shown that healthy individuals exhibit a positivity bias when inferring the causes of evaluative feedback on their performance. They tend to attribute positive feedback internally (e.g., to their own abilities) but negative feedback externally (e.g., to environmental factors). However, all empirical demonstrations of this bias suffer from at least one of the three following drawbacks: First, participants directly judge explicit causes for their performance. Second, participants have to imagine events instead of experiencing them. Third, participants assess their performance only after receiving feedback and thus differences in baseline assessments cannot be excluded. It is therefore unclear whether the classically reported positivity bias generalizes to setups without these drawbacks. Here, we aimed at establishing the relevance of attributions for decision-making by showing an attribution-related positivity bias in a decision-making task. We developed a novel task, which allowed us to test how participants changed their evaluations in response to positive and negative feedback about performance. Specifically, we used videos of actors expressing different facial emotional expressions. Participants were first asked to evaluate the actors' credibility in expressing a particular emotion. After this initial rating, participants performed an emotion recognition task and did--or did not--receive feedback on their veridical performance. Finally, participants re-rated the actors' credibility, which provided a measure of how they changed their evaluations after feedback. Attribution theory predicts that participants change their evaluations of the actors' credibility toward the positive after receiving positive performance feedback and toward the negative after negative performance feedback. Our results were in line with this prediction. A control condition without feedback showed that correct or incorrect performance

Burnout is associated with changes in error and feedback processing.

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Gajewski, Patrick D; Boden, Sylvia; Freude, Gabriele; Potter, Guy G; Falkenstein, Michael

2017-10-01

Burnout is a pattern of complaints in individuals with emotionally demanding jobs that is often seen as a precursor of depression. One often reported symptom of burnout is cognitive decline. To analyze cognitive control and to differentiate between subclinical burnout and mild to moderate depression a double-blinded study was conducted that investigates changes in the processing of performance errors and feedback in a task switching paradigm. Fifty-one of 76 employees from emotionally demanding jobs showed a sufficient number of errors to be included in the analysis. The sample was subdivided into groups with low (EE-) and high (EE+) emotional exhaustion and no (DE-) and mild to moderate depression (DE+). The behavioral data did not significantly differ between the groups. In contrast, in the EE+ group, the error negativity (Ne/ERN) was enhanced while the error positivity (Pe) did not differ between the EE+ and EE- groups. After negative feedback the feedback-related negativity (FRN) was enhanced, while the subsequent positivity (FRP) was reduced in EE+ relative to EE-. None of these effects were observed in the DE+ vs. DE-. These results suggest an upregulation of error and negative feedback processing, while the later processing of negative feedback was attenuated in employees with subclinical burnout but not in mild to moderate depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Negative plant-soil feedbacks increase with plant abundance, and are unchanged by competition

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John L. Maron; Alyssa Laney Smith; Yvette K. Ortega; Dean E. Pearson; Ragan M. Callaway

2016-01-01

Plant-soil feedbacks and interspecific competition are ubiquitous interactions that strongly influence the performance of plants. Yet few studies have examined whether the strength of these interactions corresponds with the abundance of plant species in the field, or whether feedbacks and competition interact in ways that either ameliorate or exacerbate their...

SRY-box-containing gene 2 regulation of nuclear receptor tailless (Tlx) transcription in adult neural stem cells.

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Shimozaki, Koji; Zhang, Chun-Li; Suh, Hoonkyo; Denli, Ahmet M; Evans, Ronald M; Gage, Fred H

2012-02-17

Adult neurogenesis is maintained by self-renewable neural stem cells (NSCs). Their activity is regulated by multiple signaling pathways and key transcription factors. However, it has been unclear whether these factors interplay with each other at the molecular level. Here we show that SRY-box-containing gene 2 (Sox2) and nuclear receptor tailless (TLX) form a molecular network in adult NSCs. We observed that both Sox2 and TLX proteins bind to the upstream region of Tlx gene. Sox2 positively regulates Tlx expression, whereas the binding of TLX to its own promoter suppresses its transcriptional activity in luciferase reporter assays. Such TLX-mediated suppression can be antagonized by overexpressing wild-type Sox2 but not a mutant lacking the transcriptional activation domain. Furthermore, through regions involved in DNA-binding activity, Sox2 and TLX physically interact to form a complex on DNAs that contain a consensus binding site for TLX. Finally, depletion of Sox2 revealed the potential negative feedback loop of TLX expression that is antagonized by Sox2 in adult NSCs. These data suggest that Sox2 plays an important role in Tlx transcription in cultured adult NSCs.

SRY-box-containing Gene 2 Regulation of Nuclear Receptor Tailless (Tlx) Transcription in Adult Neural Stem Cells*

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Shimozaki, Koji; Zhang, Chun-Li; Suh, Hoonkyo; Denli, Ahmet M.; Evans, Ronald M.; Gage, Fred H.

2012-01-01

Adult neurogenesis is maintained by self-renewable neural stem cells (NSCs). Their activity is regulated by multiple signaling pathways and key transcription factors. However, it has been unclear whether these factors interplay with each other at the molecular level. Here we show that SRY-box-containing gene 2 (Sox2) and nuclear receptor tailless (TLX) form a molecular network in adult NSCs. We observed that both Sox2 and TLX proteins bind to the upstream region of Tlx gene. Sox2 positively regulates Tlx expression, whereas the binding of TLX to its own promoter suppresses its transcriptional activity in luciferase reporter assays. Such TLX-mediated suppression can be antagonized by overexpressing wild-type Sox2 but not a mutant lacking the transcriptional activation domain. Furthermore, through regions involved in DNA-binding activity, Sox2 and TLX physically interact to form a complex on DNAs that contain a consensus binding site for TLX. Finally, depletion of Sox2 revealed the potential negative feedback loop of TLX expression that is antagonized by Sox2 in adult NSCs. These data suggest that Sox2 plays an important role in Tlx transcription in cultured adult NSCs. PMID:22194602

Effects of stochastic time-delayed feedback on a dynamical system modeling a chemical oscillator

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González Ochoa, Héctor O.; Perales, Gualberto Solís; Epstein, Irving R.; Femat, Ricardo

2018-05-01

We examine how stochastic time-delayed negative feedback affects the dynamical behavior of a model oscillatory reaction. We apply constant and stochastic time-delayed negative feedbacks to a point Field-Körös-Noyes photosensitive oscillator and compare their effects. Negative feedback is applied in the form of simulated inhibitory electromagnetic radiation with an intensity proportional to the concentration of oxidized light-sensitive catalyst in the oscillator. We first characterize the system under nondelayed inhibitory feedback; then we explore and compare the effects of constant (deterministic) versus stochastic time-delayed feedback. We find that the oscillatory amplitude, frequency, and waveform are essentially preserved when low-dispersion stochastic delayed feedback is used, whereas small but measurable changes appear when a large dispersion is applied.

The Facilitatory Effect of Negative Feedback on the Emergence of Analogical Reasoning Abilities

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Ball, Linden J.; Hoyle, Alison M.; Towse, Andrea S.

2010-01-01

This paper focuses on the development of analogical reasoning abilities in 5- and 6-year-old children. Our particular interest relates to the way in which analogizing is influenced by the provision of task-based feedback coupled with a self-explanation requirement. Both feedback and self-explanation provide children with opportunities to engage in…

A switch from a gradient to a threshold mode in the regulation of a transcriptional cascade promotes robust execution of meiosis in budding yeast.

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Vyacheslav Gurevich

Full Text Available Tight regulation of developmental pathways is of critical importance to all organisms, and is achieved by a transcriptional cascade ensuring the coordinated expression of sets of genes. We aimed to explore whether a strong signal is required to enter and complete a developmental pathway, by using meiosis in budding yeast as a model. We demonstrate that meiosis in budding yeast is insensitive to drastic changes in the levels of its consecutive positive regulators (Ime1, Ime2, and Ndt80. Entry into DNA replication is not correlated with the time of transcription of the early genes that regulate this event. Entry into nuclear division is directly regulated by the time of transcription of the middle genes, as premature transcription of their activator NDT80, leads to a premature entry into the first meiotic division, and loss of coordination between DNA replication and nuclear division. We demonstrate that Cdk1/Cln3 functions as a negative regulator of Ime2, and that ectopic expression of Cln3 delays entry into nuclear division as well as NDT80 transcription. Because Ime2 functions as a positive regulator for premeiotic DNA replication and NDT80 transcription, as well as a negative regulator of Cdk/Cln, we suggest that a double negative feedback loop between Ime2 and Cdk1/Cln3 promotes a bistable switch from the cell cycle to meiosis. Moreover, our results suggest a regulatory mode switch that ensures robust meiosis as the transcription of the early meiosis-specific genes responds in a graded mode to Ime1 levels, whereas that of the middle and late genes as well as initiation of DNA replication, are regulated in a threshold mode.

Positivity effect in healthy aging in observational but not active feedback-learning.

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Bellebaum, Christian; Rustemeier, Martina; Daum, Irene

2012-01-01

The present study investigated the impact of healthy aging on the bias to learn from positive or negative performance feedback in observational and active feedback learning. In active learning, a previous study had already shown a negative learning bias in healthy seniors older than 75 years, while no bias was found for younger seniors. However, healthy aging is accompanied by a 'positivity effect', a tendency to primarily attend to stimuli with positive valence. Based on recent findings of dissociable neural mechanisms in active and observational feedback learning, the positivity effect was hypothesized to influence older participants' observational feedback learning in particular. In two separate experiments, groups of young (mean age 27) and older participants (mean age 60 years) completed an observational or active learning task designed to differentially assess positive and negative learning. Older but not younger observational learners showed a significant bias to learn better from positive than negative feedback. In accordance with previous findings, no bias was found for active learning. This pattern of results is discussed in terms of differences in the neural underpinnings of active and observational learning from performance feedback.

Younger but not older adults benefit from salient feedback during learning

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Michael eHerbert

2011-08-01

Full Text Available Older adults are impaired in reinforcement learning (RL when feedback is partially ambiguous (e.g., Eppinger and Kray, 2011. In this study we examined whether older adults benefit from salient feedback information during learning. We used an electrophysiological approach and investigated 15 younger and 15 older adults with a RL task in which they had to learn stimulus-response associations under two learning conditions. In the positive learning conditions, participants could gain 50 Cents for a correct response but did not gain or lose money (*00 Cent for an incorrect response. In negative learning conditions, they could lose 50 Cents for an incorrect response but did not gain or lose money (*00 Cent for a correct response. As the identical outcome 00 Cent is either better or worse than the alternative outcome depending on the learning condition, this feedback type is ambiguous. To examine the influence of feedback salience we compared this condition with a condition in which positive and negative outcomes were color-coded and thereby clearly separable. The behavioral results indicated that younger adults reached higher accuracy levels under salient feedback conditions. Moreover, the error-related negativity (ERN and the feedback-related negativity (FRN for losses were larger if the good-bad dimension of feedback was salient. Hence, in younger adults salient feedback facilitates the rapid evaluation of outcomes on a good-bad dimension and by this supports learning. In contrast, for older adults we obtained neither behavioral nor electrophysiological effects of feedback salience. The older adults’ performance monitoring system therefore appears less flexible in integrating additional information in this evaluation process.

Decorrelation of Neural-Network Activity by Inhibitory Feedback

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Einevoll, Gaute T.; Diesmann, Markus

2012-01-01

Correlations in spike-train ensembles can seriously impair the encoding of information by their spatio-temporal structure. An inevitable source of correlation in finite neural networks is common presynaptic input to pairs of neurons. Recent studies demonstrate that spike correlations in recurrent neural networks are considerably smaller than expected based on the amount of shared presynaptic input. Here, we explain this observation by means of a linear network model and simulations of networks of leaky integrate-and-fire neurons. We show that inhibitory feedback efficiently suppresses pairwise correlations and, hence, population-rate fluctuations, thereby assigning inhibitory neurons the new role of active decorrelation. We quantify this decorrelation by comparing the responses of the intact recurrent network (feedback system) and systems where the statistics of the feedback channel is perturbed (feedforward system). Manipulations of the feedback statistics can lead to a significant increase in the power and coherence of the population response. In particular, neglecting correlations within the ensemble of feedback channels or between the external stimulus and the feedback amplifies population-rate fluctuations by orders of magnitude. The fluctuation suppression in homogeneous inhibitory networks is explained by a negative feedback loop in the one-dimensional dynamics of the compound activity. Similarly, a change of coordinates exposes an effective negative feedback loop in the compound dynamics of stable excitatory-inhibitory networks. The suppression of input correlations in finite networks is explained by the population averaged correlations in the linear network model: In purely inhibitory networks, shared-input correlations are canceled by negative spike-train correlations. In excitatory-inhibitory networks, spike-train correlations are typically positive. Here, the suppression of input correlations is not a result of the mere existence of correlations between

clockwork orange encodes a transcriptional repressor important for circadian clock amplitude in Drosophila

OpenAIRE

Lim, Chunghun; Chung, Brian Y.; Pitman, Jena L.; McGill, Jermaine J.; Pradhan, Suraj; Lee, Jongbin; Keegan, Kevin P.; Choe, Joonho; Allada, Ravi

2007-01-01

Gene transcription is a central timekeeping process in animal clocks. In Drosophila, the basic helix-loop helix (bHLH)-PAS transcription factor heterodimer, CLOCK (CLK)/CYCLE(CYC) transcriptionally activates the clock components period (per), timeless (tim), Par domain protein 1 (Pdp1), and vrille (vri) that feedback and regulate distinct features of CLK/CYC function [1]. Microarray studies have identified numerous rhythmically expressed transcripts [2-7], some of which are potential direct C...

MicroRNA-Mediated Positive Feedback Loop and Optimized Bistable Switch in a Cancer Network Involving miR-17-92

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Li, Yichen; Li, Yumin; Zhang, Hui; Chen, Yong

2011-01-01

MicroRNAs (miRNAs) are small, noncoding RNAs that play an important role in many key biological processes, including development, cell differentiation, the cell cycle and apoptosis, as central post-transcriptional regulators of gene expression. Recent studies have shown that miRNAs can act as oncogenes and tumor suppressors depending on the context. The present work focuses on the physiological significance of miRNAs and their role in regulating the switching behavior. We illustrate an abstract model of the Myc/E2F/miR-17-92 network presented by Aguda et al. (2008), which is composed of coupling between the E2F/Myc positive feedback loops and the E2F/Myc/miR-17-92 negative feedback loop. By systematically analyzing the network in close association with plausible experimental parameters, we show that, in the presence of miRNAs, the system bistability emerges from the system, with a bistable switch and a one-way switch presented by Aguda et al. instead of a single one-way switch. Moreover, the miRNAs can optimize the switching process. The model produces a diverse array of response-signal behaviors in response to various potential regulating scenarios. The model predicts that this transition exists, one from cell death or the cancerous phenotype directly to cell quiescence, due to the existence of miRNAs. It was also found that the network involving miR-17-92 exhibits high noise sensitivity due to a positive feedback loop and also maintains resistance to noise from a negative feedback loop. PMID:22022595

Task feedback effects on conflict monitoring and executive control: relationship to subclinical measures of depression.

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Holmes, Avram J; Pizzagalli, Diego A

2007-02-01

Emerging evidence suggests that depression is associated with executive dysfunction, particularly after committing errors or receiving negative performance feedback. To test this hypothesis, 57 participants performed two executive tasks known to elicit errors (the Simon and Stroop Tasks) during positive or negative performance feedback. Participants with elevated depressive symptoms (Beck Depression Inventory scores >or= 13) were characterized by impaired posterror and postconflict performance adjustments, especially during emotionally negative task-related feedback. Additionally, for both tasks, depressive symptoms were inversely related to postconflict reaction time adjustments following negative, but not positive, feedback. These findings suggest that subclinical depression is associated with impairments in behavioral adjustments after internal (perceived failure) and external feedback about deficient task performance. (c) 2007 APA, all rights reserved.

Oscillatory Dynamics of the Extracellular Signal-regulated Kinase Pathway

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Shankaran, Harish; Wiley, H. S.

2010-12-01

The extracellular signal-regulated kinase (ERK) pathway is a central signaling pathway in development and disease and is regulated by multiple negative and positive feedback loops. Recent studies have shown negative feedback from ERK to upstream regulators can give rise to biochemical oscillations with a periodicity of between 15-30 minutes. Feedback due to the stimulated transcription of negative regulators of the ERK pathway can also give rise to transcriptional oscillations with a periodicity of 1-2h. The biological significance of these oscillations is not clear, but recent evidence suggests that transcriptional oscillations participate in developmental processes, such as somite formation. Biochemical oscillations are more enigmatic, but could provide a mechanism for encoding different types of inputs into a common signaling pathway.

Promoter proximal polyadenylation sites reduce transcription activity

DEFF Research Database (Denmark)

Andersen, Pia Kjølhede; Lykke-Andersen, Søren; Jensen, Torben Heick

2012-01-01

Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site......, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites...... on transcription requires promoter proximity, as demonstrated using artificial constructs and supported by a genome-wide data set. Importantly, transcription down-regulation can be recapitulated in a gene context devoid of splice sites by placing a functional bona fide pA site/transcription terminator within ∼500...

Modelling reveals kinetic advantages of co-transcriptional splicing.

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Stuart Aitken

2011-10-01

Full Text Available Messenger RNA splicing is an essential and complex process for the removal of intron sequences. Whereas the composition of the splicing machinery is mostly known, the kinetics of splicing, the catalytic activity of splicing factors and the interdependency of transcription, splicing and mRNA 3' end formation are less well understood. We propose a stochastic model of splicing kinetics that explains data obtained from high-resolution kinetic analyses of transcription, splicing and 3' end formation during induction of an intron-containing reporter gene in budding yeast. Modelling reveals co-transcriptional splicing to be the most probable and most efficient splicing pathway for the reporter transcripts, due in part to a positive feedback mechanism for co-transcriptional second step splicing. Model comparison is used to assess the alternative representations of reactions. Modelling also indicates the functional coupling of transcription and splicing, because both the rate of initiation of transcription and the probability that step one of splicing occurs co-transcriptionally are reduced, when the second step of splicing is abolished in a mutant reporter.

Modelling reveals kinetic advantages of co-transcriptional splicing.

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Aitken, Stuart; Alexander, Ross D; Beggs, Jean D

2011-10-01

Messenger RNA splicing is an essential and complex process for the removal of intron sequences. Whereas the composition of the splicing machinery is mostly known, the kinetics of splicing, the catalytic activity of splicing factors and the interdependency of transcription, splicing and mRNA 3' end formation are less well understood. We propose a stochastic model of splicing kinetics that explains data obtained from high-resolution kinetic analyses of transcription, splicing and 3' end formation during induction of an intron-containing reporter gene in budding yeast. Modelling reveals co-transcriptional splicing to be the most probable and most efficient splicing pathway for the reporter transcripts, due in part to a positive feedback mechanism for co-transcriptional second step splicing. Model comparison is used to assess the alternative representations of reactions. Modelling also indicates the functional coupling of transcription and splicing, because both the rate of initiation of transcription and the probability that step one of splicing occurs co-transcriptionally are reduced, when the second step of splicing is abolished in a mutant reporter.

A Negative Feedback Loop Between Autophagy and Immune Responses in Mycobacterium leprae Infection.

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Ma, Yuelong; Zhang, Li; Lu, Jie; Shui, Tiejun; Chen, Jia; Yang, Jun; Yuan, Joanna; Liu, Yeqiang; Yang, Degang

2017-01-01

The obligate intracellular bacterium Mycobacterium leprae is the causative agent of leprosy and primarily infects macrophages, leading to irreversible nerve damage and deformities. So far, the underlying reasons allowing M. leprae to persist and propagate in macrophages, despite the presence of cellular immunity, are still a mystery. Here, we investigated the role of autophagy, a cellular process that degrades cytosolic materials and intracellular pathogens, in M. leprae infection. We found that live M. leprae infection of macrophages resulted in significantly elevated autophagy level. However, macrophages with high autophagy levels preferentially expressed lower levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-12, and tumor necrosis factor-α, and preferentially primed anti-inflammatory T cells responses, characterized by high IL-10 and low interferon-γ, granzyme B, and perforin responses. These anti-inflammatory T cells could suppress further induction of autophagy, leading to improved survival of intracellular M. leprae in infected macrophages. Therefore, these data demonstrated that although autophagy had a role in eliminating intracellular pathogens, the induction of autophagy resulted in anti-inflammatory immune responses, which suppressed autophagy in a negative feedback loop and allowed the persistence of M. leprae.

Timing matters: The impact of immediate and delayed feedback on artificial language learning

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Bertram Opitz

2011-02-01

Full Text Available In the present experiment, we used event-related potentials (ERP to investigate the role of immediate and delayed feedback in an artificial grammar learning task. Two groups of participants were engaged in classifying non-word strings according to an underlying rule system, not known to the participants. Visual feedback was provided after each classification either immediately or with a short delay of one second. Both groups were able to learn the artificial grammar system as indicated by an increase in classification performance. However, the gain in performance was significantly larger for the group receiving immediate feedback as compared to the group receiving delayed feedback. Learning was accompanied by an increase in P300 activity in the ERP for delayed as compared to immediate feedback. Irrespective of feedback delay, both groups exhibited learning related decreases in the feedback-related positivity (FRP elicited by positive feedback only. The feedback-related negativity (FRN, however, remained constant over the course of learning. These results suggest, first, that delayed feedback is less effective for artificial grammar learning as task requirements are very demanding, and second, that the FRP elicited by positive prediction errors decreases with learning while the FRN to negative prediction errors is elicited in an all-or-none fashion by negative feedback throughout the entire experiment.

Effects of achievement goals on challenge seeking and feedback processing: behavioral and FMRI evidence.

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Woogul Lee

Full Text Available We conducted behavioral and functional magnetic resonance imaging (fMRI research to investigate the effects of two types of achievement goals--mastery goals and performance-approach goals--on challenge seeking and feedback processing. The results of the behavioral experiment indicated that mastery goals were associated with a tendency to seek challenge, both before and after experiencing difficulty during task performance, whereas performance-approach goals were related to a tendency to avoid challenge after encountering difficulty during task performance. The fMRI experiment uncovered a significant decrease in ventral striatal activity when participants received negative feedback for any task type and both forms of achievement goals. During the processing of negative feedback for the rule-finding task, performance-approach-oriented participants showed a substantial reduction in activity in the dorsolateral prefrontal cortex (DLPFC and the frontopolar cortex, whereas mastery-oriented participants showed little change. These results suggest that performance-approach-oriented participants are less likely to either recruit control processes in response to negative feedback or focus on task-relevant information provided alongside the negative feedback. In contrast, mastery-oriented participants are more likely to modulate aversive valuations to negative feedback and focus on the constructive elements of feedback in order to attain their task goals. We conclude that performance-approach goals lead to a reluctant stance towards difficulty, while mastery goals encourage a proactive stance.

Nascent-Seq reveals novel features of mouse circadian transcriptional regulation

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Menet, Jerome S; Rodriguez, Joseph; Abruzzi, Katharine C; Rosbash, Michael

2012-01-01

A substantial fraction of the metazoan transcriptome undergoes circadian oscillations in many cells and tissues. Based on the transcription feedback loops important for circadian timekeeping, it is commonly assumed that this mRNA cycling reflects widespread transcriptional regulation. To address this issue, we directly measured the circadian dynamics of mouse liver transcription using Nascent-Seq (genome-wide sequencing of nascent RNA). Although many genes are rhythmically transcribed, many rhythmic mRNAs manifest poor transcriptional rhythms, indicating a prominent contribution of post-transcriptional regulation to circadian mRNA expression. This analysis of rhythmic transcription also showed that the rhythmic DNA binding profile of the transcription factors CLOCK and BMAL1 does not determine the transcriptional phase of most target genes. This likely reflects gene-specific collaborations of CLK:BMAL1 with other transcription factors. These insights from Nascent-Seq indicate that it should have broad applicability to many other gene expression regulatory issues. DOI: http://dx.doi.org/10.7554/eLife.00011.001 PMID:23150795

Social closeness and feedback modulate susceptibility to the framing effect

Science.gov (United States)

Sip, Kamila E.; Smith, David V.; Porcelli, Anthony J.; Kar, Kohitij; Delgado, Mauricio R.

2014-01-01

Although, we often seek social feedback from others to help us make decisions, little is known about how social feedback affects decisions under risk, particularly from a close peer. We conducted two experiments using an established framing task to probe how decision making is modulated by social feedback valence (positive, negative) and the level of closeness with feedback provider (friend, confederate). Participants faced mathematically equivalent decisions framed as either an opportunity to keep (gain frame) or lose (loss frame) part of an initial endowment. Periodically, participants were provided with positive (e.g., “Nice!”) or negative (e.g., “Lame!”) feedback about their choices. Such feedback was provided by either a confederate (Experiment 1), or a gender-matched close friend (Experiment 2). As expected, the framing effect was observed in both experiments. Critically, an individual’s susceptibility to the framing effect was modulated by the valence of the social feedback, but only when the feedback provider was a close friend. This effect was reflected in the activation patterns of ventromedial prefrontal cortex and posterior cingulate cortex, regions involved in complex decision making. Taken together, these results highlight social closeness as an important factor in understanding the impact of social feedback on neural mechanisms of decision making. PMID:25074501

Ring a bell? Adaptive Auditory Game Feedback to Sustain Performance in Stroke Rehabilitation

DEFF Research Database (Denmark)

Hald, Kasper; Knoche, Hendrik

2016-01-01

This paper investigates the effect of adaptive auditory feed- back on continued player performance for stroke patients in a Whack- a-Mole style tablet game. The feedback consisted of accumulatively in- creasing the pitch of positive feedback sounds on tasks with fast reaction time and resetting...... it after slow reaction times. The analysis was based on data was obtained in a field trial with lesion patients during their regular rehabilitation. The auditory feedback events were categorized by feedback type (positive/negative) and the associated pitch change of ei- ther high or low magnitude. Both...... feedback type and magnitude had a significant effect on players performance. Negative feedback improved re- action time on the subsequent hit by 0.42 second and positive feedback impaired performance by 0.15 seconds....

Feedback is good or bad? Medical residents’ points of view on feedback in clinical education

Directory of Open Access Journals (Sweden)

LEILA BAZRAFKAN

2013-04-01

Full Text Available Introduction: Feedback is very important in education and can help quality in the training process and orient the trainees in clinical contexts. This study aimed to assess the residents’ points of view about feedback in clinical education at Shiraz University of Medical Sciences. Methods: The sample of this study included 170 medical residents attending medical workshops in Shiraz University of Medical Sciences. The residents filled a valid and reliable questionnaire containing 21 items on their perceptions of the feedback they got throughout the workshops. The data were analyzed using SPSS version 14. Results: The study revealed that residents, generally, have a positive perception of feedback in their training. The highest score belonged to the items such as “feedback was applicable to future work”, “feedback corrected my behavior”, “feedback worked as a motivation for education” and “feedback was specific in one subject”. Residents who had a negative feedback experience also increased their efforts to learn. The Surgery residents acquired the highest scores while radiology residents got the lowest. The difference between these groups was statistically significant (P = 0.000. Conclusion: The highest mean score belonged to internal medicine residents. This shows that residents believe that obstetrics & gynecology ward is a ward in which the formative assessment is much more powerful in comparison to the other three major wards. The surgery ward received the lowest score for formative assessment and this shows that the feedback in surgery ward is very low.

HECT E3 Ubiquitin Ligase Itch Functions as a Novel Negative Regulator of Gli-Similar 3 (Glis3 Transcriptional Activity.

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Gary T ZeRuth

Full Text Available The transcription factor Gli-similar 3 (Glis3 plays a critical role in the generation of pancreatic ß cells and the regulation insulin gene transcription and has been implicated in the development of several pathologies, including type 1 and 2 diabetes and polycystic kidney disease. However, little is known about the proteins and posttranslational modifications that regulate or mediate Glis3 transcriptional activity. In this study, we identify by mass-spectrometry and yeast 2-hybrid analyses several proteins that interact with the N-terminal region of Glis3. These include the WW-domain-containing HECT E3 ubiquitin ligases, Itch, Smurf2, and Nedd4. The interaction between Glis3 and the HECT E3 ubiquitin ligases was verified by co-immunoprecipitation assays and mutation analysis. All three proteins interact through their WW-domains with a PPxY motif located in the Glis3 N-terminus. However, only Itch significantly contributed to Glis3 polyubiquitination and reduced Glis3 stability by enhancing its proteasomal degradation. Itch-mediated degradation of Glis3 required the PPxY motif-dependent interaction between Glis3 and the WW-domains of Itch as well as the presence of the Glis3 zinc finger domains. Transcription analyses demonstrated that Itch dramatically inhibited Glis3-mediated transactivation and endogenous Ins2 expression by increasing Glis3 protein turnover. Taken together, our study identifies Itch as a critical negative regulator of Glis3-mediated transcriptional activity. This regulation provides a novel mechanism to modulate Glis3-driven gene expression and suggests that it may play a role in a number of physiological processes controlled by Glis3, such as insulin transcription, as well as in Glis3-associated diseases.

A positive feedback loop links opposing functions of P-TEFb/Cdk9 and histone H2B ubiquitylation to regulate transcript elongation in fission yeast.

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Miriam Sansó

Full Text Available Transcript elongation by RNA polymerase II (RNAPII is accompanied by conserved patterns of histone modification. Whereas histone modifications have established roles in transcription initiation, their functions during elongation are not understood. Mono-ubiquitylation of histone H2B (H2Bub1 plays a key role in coordinating co-transcriptional histone modification by promoting site-specific methylation of histone H3. H2Bub1 also regulates gene expression through an unidentified, methylation-independent mechanism. Here we reveal bidirectional communication between H2Bub1 and Cdk9, the ortholog of metazoan positive transcription elongation factor b (P-TEFb, in the fission yeast Schizosaccharomyces pombe. Chemical and classical genetic analyses indicate that lowering Cdk9 activity or preventing phosphorylation of its substrate, the transcription processivity factor Spt5, reduces H2Bub1 in vivo. Conversely, mutations in the H2Bub1 pathway impair Cdk9 recruitment to chromatin and decrease Spt5 phosphorylation. Moreover, an Spt5 phosphorylation-site mutation, combined with deletion of the histone H3 Lys4 methyltransferase Set1, phenocopies morphologic and growth defects due to H2Bub1 loss, suggesting independent, partially redundant roles for Cdk9 and Set1 downstream of H2Bub1. Surprisingly, mutation of the histone H2B ubiquitin-acceptor residue relaxes the Cdk9 activity requirement in vivo, and cdk9 mutations suppress cell-morphology defects in H2Bub1-deficient strains. Genome-wide analyses by chromatin immunoprecipitation also demonstrate opposing effects of Cdk9 and H2Bub1 on distribution of transcribing RNAPII. Therefore, whereas mutual dependence of H2Bub1 and Spt5 phosphorylation indicates positive feedback, mutual suppression by cdk9 and H2Bub1-pathway mutations suggests antagonistic functions that must be kept in balance to regulate elongation. Loss of H2Bub1 disrupts that balance and leads to deranged gene expression and aberrant cell

Detecting vegetation-precipitation feedbacks in mid-Holocene North Africa from two climate models

Energy Technology Data Exchange (ETDEWEB)

Wang, Yi; Notaro, Michael; Liu, Zhengyu; Gallimore, Robert; Levis, Samuel; Kutzbach, John E.

2008-03-31

Using two climate-vegetation model simulations from the Fast Ocean Atmosphere Model (FOAM) and the Community Climate System Model (CCSM, version 2), we investigate vegetation-precipitation feedbacks across North Africa during the mid-Holocene. From mid-Holocene snapshot runs of FOAM and CCSM2, we detect a negative feedback at the annual timescale with our statistical analysis. Using the Monte- Carlo bootstrap method, the annual negative feedback is further confirmed to be significant in both simulations. Additional analysis shows that this negative interaction is partially caused by the competition between evaporation and transpiration in North African grasslands. Furthermore, we find the feedbacks decrease with increasing timescales, and change signs from positive to negative at increasing timescales in FOAM. The proposed mechanism for this sign switch is associated with the different persistent timescales of upper and lower soil water contents, and their interactions with vegetation and atmospheric precipitation.

Different Electrophysiological Responses to Informative Value of Feedback Between Children and Adults

Directory of Open Access Journals (Sweden)

Bin Du

2018-04-01

Full Text Available The ability to learn from feedback is important for children’s adaptive behavior and school learning. Feedback has two main components, informative value and valence. How to disentangle these two components and what is the developmental neural correlates of using the informative value of feedback is still an open question. In this study, 23 children (7–10 years old and 19 adults (19–22 years old were asked to perform a rule induction task, in which they were required to find a rule, based on the informative value of feedback. Behavioral results indicated that the likelihood of correct searching behavior under negative feedback was low for children. Event-related potentials showed that (1 the effect of valence was processed in a wide time window, particularly in the N2 component; (2 the encoding process of the informative value of negative feedback began later for children than for adults; (3 a clear P300 was observed for adults; for children, however, P300 was absent in the frontal region; and (4 children processed the informative value of feedback chiefly in the left sites during the P300 time window, whereas adults did not show this laterality. These results suggested that children were less sensitive to the informative value of negative feedback possibly because of the immature brain.

Using a Feedback Environment to Improve Creative Performance: A Dynamic Affect Perspective.

Science.gov (United States)

Gong, Zhenxing; Zhang, Na

2017-01-01

Prior research on feedback and creative performance has neglected the dynamic nature of affect and has focused only on the influence of positive affect. We argue that creative performance is the result of a dynamic process in which a person experiences a phase of negative affect and subsequently enters a state of high positive affect that is influenced by the feedback environment. Hierarchical regression was used to analyze a sample of 264 employees from seven industry firms. The results indicate that employees' perceptions of a supportive supervisor feedback environment indirectly influence their level of creative performance through positive affect (t2); the negative affect (t1) moderates the relationship between positive affect (t2) and creative performance (t2), rendering the relationship more positive if negative affect (t1) is high. The change in positive affect mediates the relationship between the supervisor feedback environment and creative performance; a decrease in negative affect moderates the relationship between increased positive affect and creative performance, rendering the relationship more positive if the decrease in negative affect is large. The implications for improving the creative performances of employees are further discussed.

Using a Feedback Environment to Improve Creative Performance: A Dynamic Affect Perspective

Directory of Open Access Journals (Sweden)

Zhenxing Gong

2017-08-01

Full Text Available Prior research on feedback and creative performance has neglected the dynamic nature of affect and has focused only on the influence of positive affect. We argue that creative performance is the result of a dynamic process in which a person experiences a phase of negative affect and subsequently enters a state of high positive affect that is influenced by the feedback environment. Hierarchical regression was used to analyze a sample of 264 employees from seven industry firms. The results indicate that employees’ perceptions of a supportive supervisor feedback environment indirectly influence their level of creative performance through positive affect (t2; the negative affect (t1 moderates the relationship between positive affect (t2 and creative performance (t2, rendering the relationship more positive if negative affect (t1 is high. The change in positive affect mediates the relationship between the supervisor feedback environment and creative performance; a decrease in negative affect moderates the relationship between increased positive affect and creative performance, rendering the relationship more positive if the decrease in negative affect is large. The implications for improving the creative performances of employees are further discussed.

Positive Feedback From Male Authority Figures Boosts Women's Math Outcomes.

Science.gov (United States)

Park, Lora E; Kondrak, Cheryl L; Ward, Deborah E; Streamer, Lindsey

2018-03-01

People often search for cues in the environment to determine whether or not they will be judged or treated negatively based on their social identities. Accordingly, feedback from gatekeepers-members of majority groups who hold authority and power in a field-may be an especially important cue for those at risk of experiencing social identity threat, such as women in math settings. Across a series of studies, women who received positive ("Good job!") versus objective (score only) feedback from a male (vs. female) authority figure in math reported greater confidence; belonging; self-efficacy; more favorable Science, Technology, Engineering, and Mathematics (STEM) attitudes/identification/interest; and greater implicit identification with math. Men were affected only by the type of math feedback they received, not by the source of feedback. A meta-analysis across studies confirmed results. Together, these findings suggest that positive feedback from gatekeepers is an important situational cue that can improve the outcomes of negatively stereotyped groups.

Feedback regulation of TGF-β signaling.

Science.gov (United States)

Yan, Xiaohua; Xiong, Xiangyang; Chen, Ye-Guang

2018-01-01

Transforming growth factor beta (TGF-β) is a multi-functional polypeptide that plays a critical role in regulating a broad range of cellular functions and physiological processes. Signaling is initiated when TGF-β ligands bind to two types of cell membrane receptors with intrinsic Ser/Thr kinase activity and transmitted by the intracellular Smad proteins, which act as transcription factors to regulate gene expression in the nucleus. Although it is relatively simple and straight-forward, this TGF-β/Smad pathway is regulated by various feedback loops at different levels, including the ligand, the receptor, Smads and transcription, and is thus fine-tuned in terms of signaling robustness, duration, specificity, and plasticity. The precise control gives rise to versatile and context-dependent pathophysiological functions. In this review, we firstly give an overview of TGF-β signaling, and then discuss how each step of TGF-β signaling is finely controlled by distinct modes of feedback mechanisms, involving both protein regulators and miRNAs. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Social closeness and feedback modulate susceptibility to the framing effect

OpenAIRE

Sip, Kamila E.; Smith, David V.; Porcelli, Anthony J.; Kar, Kohitij; Delgado, Mauricio R.

2014-01-01

Although, we often seek social feedback from others to help us make decisions, little is known about how social feedback affects decisions under risk, particularly from a close peer. We conducted two experiments using an established framing task to probe how decision making is modulated by social feedback valence (positive, negative) and the level of closeness with feedback provider (friend, confederate). Participants faced mathematically equivalent decisions framed as either an opportunity t...

Atmospheric radiative feedbacks associated with transient climate change and climate variability

Energy Technology Data Exchange (ETDEWEB)

Colman, Robert A.; Power, Scott B. [Bureau of Meteorology, Centre for Australian Weather and Climate Research, GPO Box 1289, Melbourne, VIC (Australia)

2010-06-15

This study examines in detail the 'atmospheric' radiative feedbacks operating in a coupled General Circulation Model (GCM). These feedbacks (defined as the change in top of atmosphere radiation per degree of global surface temperature change) are due to responses in water vapour, lapse rate, clouds and surface albedo. Two types of radiative feedback in particular are considered: those arising from century scale 'transient' warming (from a 1% per annum compounded CO{sub 2} increase), and those operating under the model's own unforced 'natural' variability. The time evolution of the transient (or 'secular') feedbacks is first examined. It is found that both the global strength and the latitudinal distributions of these feedbacks are established within the first two or three decades of warming, and thereafter change relatively little out to 100 years. They also closely approximate those found under equilibrium warming from a 'mixed layer' ocean version of the same model forced by a doubling of CO{sub 2}. These secular feedbacks are then compared with those operating under unforced (interannual) variability. For water vapour, the interannual feedback is only around two-thirds the strength of the secular feedback. The pattern reveals widespread regions of negative feedback in the interannual case, in turn resulting from patterns of circulation change and regions of decreasing as well as increasing surface temperature. Considering the vertical structure of the two, it is found that although positive net mid to upper tropospheric contributions dominate both, they are weaker (and occur lower) under interannual variability than under secular change and are more narrowly confined to the tropics. Lapse rate feedback from variability shows weak negative feedback over low latitudes combined with strong positive feedback in mid-to-high latitudes resulting in no net global feedback - in contrast to the dominant negative low

Overlooked runaway feedback in the marine nitrogen cycle: the vicious cycle

Directory of Open Access Journals (Sweden)

A. Landolfi

2013-03-01

Full Text Available The marine nitrogen (N inventory is thought to be stabilized by negative feedback mechanisms that reduce N inventory excursions relative to the more slowly overturning phosphorus inventory. Using a global biogeochemical ocean circulation model we show that negative feedbacks stabilizing the N inventory cannot persist if a close spatial association of N2 fixation and denitrification occurs. In our idealized model experiments, nitrogen deficient waters, generated by denitrification, stimulate local N2 fixation activity. But, because of stoichiometric constraints, the denitrification of newly fixed nitrogen leads to a net loss of N. This can enhance the N deficit, thereby triggering additional fixation in a vicious cycle, ultimately leading to a runaway N loss. To break this vicious cycle, and allow for stabilizing negative feedbacks to occur, inputs of new N need to be spatially decoupled from denitrification. Our idealized model experiments suggest that factors such as iron limitation or dissolved organic matter cycling can promote such decoupling and allow for negative feedbacks that stabilize the N inventory. Conversely, close spatial co-location of N2 fixation and denitrification could lead to net N loss.

Electrophysiological Correlates of Error Monitoring and Feedback Processing in Second Language Learning.

Science.gov (United States)

Bultena, Sybrine; Danielmeier, Claudia; Bekkering, Harold; Lemhöfer, Kristin

2017-01-01

Humans monitor their behavior to optimize performance, which presumably relies on stable representations of correct responses. During second language (L2) learning, however, stable representations have yet to be formed while knowledge of the first language (L1) can interfere with learning, which in some cases results in persistent errors. In order to examine how correct L2 representations are stabilized, this study examined performance monitoring in the learning process of second language learners for a feature that conflicts with their first language. Using EEG, we investigated if L2 learners in a feedback-guided word gender assignment task showed signs of error detection in the form of an error-related negativity (ERN) before and after receiving feedback, and how feedback is processed. The results indicated that initially, response-locked negativities for correct (CRN) and incorrect (ERN) responses were of similar size, showing a lack of internal error detection when L2 representations are unstable. As behavioral performance improved following feedback, the ERN became larger than the CRN, pointing to the first signs of successful error detection. Additionally, we observed a second negativity following the ERN/CRN components, the amplitude of which followed a similar pattern as the previous negativities. Feedback-locked data indicated robust FRN and P300 effects in response to negative feedback across different rounds, demonstrating that feedback remained important in order to update memory representations during learning. We thus show that initially, L2 representations may often not be stable enough to warrant successful error monitoring, but can be stabilized through repeated feedback, which means that the brain is able to overcome L1 interference, and can learn to detect errors internally after a short training session. The results contribute a different perspective to the discussion on changes in ERN and FRN components in relation to learning, by extending the

A novel network integrating a miRNA-203/SNAI1 feedback loop which regulates epithelial to mesenchymal transition.

Directory of Open Access Journals (Sweden)

Michèle Moes

Full Text Available BACKGROUND: The majority of human cancer deaths are caused by metastasis. The metastatic dissemination is initiated by the breakdown of epithelial cell homeostasis. During this phenomenon, referred to as epithelial to mesenchymal transition (EMT, cells change their genetic and trancriptomic program leading to phenotypic and functional alterations. The challenge of understanding this dynamic process resides in unraveling regulatory networks involving master transcription factors (e.g. SNAI1/2, ZEB1/2 and TWIST1 and microRNAs. Here we investigated microRNAs regulated by SNAI1 and their potential role in the regulatory networks underlying epithelial plasticity. RESULTS: By a large-scale analysis on epithelial plasticity, we highlighted miR-203 and its molecular link with SNAI1 and the miR-200 family, key regulators of epithelial homeostasis. During SNAI1-induced EMT in MCF7 breast cancer cells, miR-203 and miR-200 family members were repressed in a timely correlated manner. Importantly, miR-203 repressed endogenous SNAI1, forming a double negative miR203/SNAI1 feedback loop. We integrated this novel miR203/SNAI1 with the known miR200/ZEB feedback loops to construct an a priori EMT core network. Dynamic simulations revealed stable epithelial and mesenchymal states, and underscored the crucial role of the miR203/SNAI1 feedback loop in state transitions underlying epithelial plasticity. CONCLUSION: By combining computational biology and experimental approaches, we propose a novel EMT core network integrating two fundamental negative feedback loops, miR203/SNAI1 and miR200/ZEB. Altogether our analysis implies that this novel EMT core network could function as a switch controlling epithelial cell plasticity during differentiation and cancer progression.

The role of feedbacks in Antarctic sea ice change

Science.gov (United States)

Feltham, D. L.; Frew, R. C.; Holland, P.

2017-12-01

The changes in Antarctic sea ice over the last thirty years have a strong seasonal dependence, and the way these changes grow in spring and decay in autumn suggests that feedbacks are strongly involved. The changes may ultimately be caused by atmospheric warming, the winds, snowfall changes, etc., but we cannot understand these forcings without first untangling the feedbacks. A highly simplified coupled sea ice -mixed layer model has been developed to investigate the importance of feedbacks on the evolution of sea ice in two contrasting regions in the Southern Ocean; the Amundsen Sea where sea ice extent has been decreasing, and the Weddell Sea where it has been expanding. The change in mixed layer depth in response to changes in the atmosphere to ocean energy flux is implicit in a strong negative feedback on ice cover changes in the Amundsen Sea, with atmospheric cooling leading to a deeper mixed layer resulting in greater entrainment of warm Circumpolar Deep Water, causing increased basal melting of sea ice. This strong negative feedback produces counter intuitive responses to changes in forcings in the Amundsen Sea. This feedback is absent in the Weddell due to the complete destratification and strong water column cooling that occurs each winter in simulations. The impact of other feedbacks, including the albedo feedback, changes in insulation due to ice thickness and changes in the freezing temperature of the mixed layer, were found to be of secondary importance compared to changes in the mixed layer depth.

Consistency Over Flattery: Self-Verification Processes Revealed in Implicit and Behavioral Responses to Feedback

OpenAIRE

Ayduk, O; Gyurak, A; Akinola, M; Mendes, WB

2013-01-01

Negative social feedback is often a source of distress. However, self-verification theory provides the counterintuitive explanation that negative feedback leads to less distress when it is consistent with chronic self-views. Drawing from this work, the present study examined the impact of receiving self-verifying feedback on outcomes largely neglected in prior research: implicit responses (i.e., physiological reactivity, facial expressions) that are difficult to consciously regulate and downs...

TetR Family Transcriptional Regulator PccD Negatively Controls Propionyl Coenzyme A Assimilation in Saccharopolyspora erythraea.

Science.gov (United States)

Xu, Zhen; Wang, Miaomiao; Ye, Bang-Ce

2017-10-15

Propanol stimulates erythromycin biosynthesis by increasing the supply of propionyl coenzyme A (propionyl-CoA), a starter unit of erythromycin production in Saccharopolyspora erythraea Propionyl-CoA is assimilated via propionyl-CoA carboxylase to methylmalonyl-CoA, an extender unit of erythromycin. We found that the addition of n -propanol or propionate caused a 4- to 16-fold increase in the transcriptional levels of the SACE_3398-3400 locus encoding propionyl-CoA carboxylase, a key enzyme in propionate metabolism. The regulator PccD was proved to be directly involved in the transcription regulation of the SACE_3398-3400 locus by EMSA and DNase I footprint analysis. The transcriptional levels of SACE_3398-3400 were upregulated 15- to 37-fold in the pccD gene deletion strain (Δ pccD ) and downregulated 3-fold in the pccD overexpression strain (WT/pIB- pccD ), indicating that PccD was a negative transcriptional regulator of SACE_3398-3400. The Δ pccD strain has a higher growth rate than that of the wild-type strain (WT) on Evans medium with propionate as the sole carbon source, whereas the growth of the WT/pIB- pccD strain was repressed. As a possible metabolite of propionate metabolism, methylmalonic acid was identified as an effector molecule of PccD and repressed its regulatory activity. A higher level of erythromycin in the Δ pccD strain was observed compared with that in the wild-type strain. Our study reveals a regulatory mechanism in propionate metabolism and suggests new possibilities for designing metabolic engineering to increase erythromycin yield. IMPORTANCE Our work has identified the novel regulator PccD that controls the expression of the gene for propionyl-CoA carboxylase, a key enzyme in propionyl-CoA assimilation in S. erythraea PccD represses the generation of methylmalonyl-CoA through carboxylation of propionyl-CoA and reveals an effect on biosynthesis of erythromycin. This finding provides novel insight into propionyl-CoA assimilation, and

Be kind to your eating disorder patients: the impact of positive and negative feedback on the explicit and implicit self-esteem of female patients with eating disorders

NARCIS (Netherlands)

Vanderlinden, J.; Kamphuis, J.H.; Slagmolen, C.; Wigboldus, D.; Pieters, G.; Probst, M.

2009-01-01

OBJECTIVE: Lack of self-esteem may play an important role in the development of eating disorders (ED). This study investigated the differential impact of positive and negative feedback on implicit and explicit self-esteem in women with an ED (N=25) as compared to women without an ED (N=29). METHOD:

Be kind to your eating disorder patients: The impact of positive and negative feedback on the explicit and implicit self-esteem of female patients with eating disorders

NARCIS (Netherlands)

Vanderlinden, J.; Kamphuis, J.H.; Slagmolen, C.J.J.; Wigboldus, D.H.J.; Pieters, G.; Probst, M.

2009-01-01

OBJECTIVE: Lack of self-esteem may play an important role in the development of eating disorders (ED). This study investigated the differential impact of positive and negative feedback on implicit and explicit self-esteem in women with an ED (N=25) as compared to women without an ED (N=29). METHOD:

An intercomparison between the surface heat flux feedback in five coupled models, COADS and the NCEP reanalysis

Energy Technology Data Exchange (ETDEWEB)

Frankignoul, C.; Kestenare, E. [Universite Pierre et Marie Curie, Institute Pierre-Simon Laplace, Laboratoire d' Oceanographie Dynamique et de Climatologie, 4 place Jussieu, 75252 Paris Cedex 05 (France); Botzet, M. [Max-Planck-Institut fuer Meteorologie, Hamburg (Germany); Carril, A.F. [Istituto Nazionale di Geofisica e Vulcanologia, Bologna (Italy); Drange, H. [Nansen Environmental and Remote Sensing Center, Bergen (Norway); Pardaens, A. [Hadley Centre for Climate Prediction and Research, Met Office (United Kingdom); Terray, L.; Sutton, R. [Department of Meteorology, University of Reading (United Kingdom)

2004-04-01

The surface heat flux feedback is estimated in the Atlantic and the extra-tropical Indo-Pacific, using monthly heat flux and sea surface temperature anomaly data from control simulations with five global climate models, and it is compared to estimates derived from COADS and the NCEP reanalysis. In all data sets, the heat flux feedback is negative nearly everywhere and damps the sea surface temperature anomalies. At extra-tropical latitudes, it is strongly dominated by the turbulent fluxes. The radiative feedback can be positive or negative, depending on location and season, but it remains small, except in some models in the tropical Atlantic. The negative heat flux feedback is strong in the mid-latitude storm tracks, exceeding 40 W m{sup -2} K{sup -1} at place, but in the Northern Hemisphere it is substantially underestimated in several models. The negative feedback weakens at high latitudes, although the models do not reproduce the weak positive feedback found in NCEP in the northern North Atlantic. The main differences are found in the tropical Atlantic where the heat flux feedback is weakly negative in some models, as in the observations, and strongly negative in others where it can exceed 30 W m{sup -2} K{sup -1} at large scales, in part because of a strong contribution of the radiative fluxes, in particular during spring. A comparison between models with similar atmospheric or oceanic components suggests that the atmospheric model is primarily responsible for the heat flux feedback differences at extra-tropical latitudes. In the tropical Atlantic, the ocean behavior plays an equal role. The differences in heat flux feedback in the tropical Atlantic are reflected in the sea surface temperature anomaly persistence, which is too small in models where the heat flux damping is large. A good representation of the heat flux feedback is thus required to simulate climate variability realistically. (orig.)

Who Deserves My Trust? Cue-Elicited Feedback Negativity Tracks Reputation Learning in Repeated Social Interactions.

Science.gov (United States)

Li, Diandian; Meng, Liang; Ma, Qingguo

2017-01-01

Trust and trustworthiness contribute to reciprocal behavior and social relationship development. To make better decisions, people need to evaluate others' trustworthiness. They often assess this kind of reputation by learning through repeated social interactions. The present event-related potential (ERP) study explored the reputation learning process in a repeated trust game where subjects made multi-round decisions of investment to different partners. We found that subjects gradually learned to discriminate trustworthy partners from untrustworthy ones based on how often their partners reciprocated the investment, which was indicated by their own investment decisions. Besides, electrophysiological data showed that the faces of the untrustworthy partners induced larger feedback negativity (FN) amplitude than those of the trustworthy partners, but only in the late phase of the game. The ERP results corresponded with the behavioral pattern and revealed that the learned trustworthiness differentiation was coded by the cue-elicited FN component. Consistent with previous research, our findings suggest that the anterior cue-elicited FN reflects the reputation appraisal and tracks the reputation learning process in social interactions.

Who Deserves My Trust? Cue-Elicited Feedback Negativity Tracks Reputation Learning in Repeated Social Interactions

Directory of Open Access Journals (Sweden)

Diandian Li

2017-06-01

Full Text Available Trust and trustworthiness contribute to reciprocal behavior and social relationship development. To make better decisions, people need to evaluate others’ trustworthiness. They often assess this kind of reputation by learning through repeated social interactions. The present event-related potential (ERP study explored the reputation learning process in a repeated trust game where subjects made multi-round decisions of investment to different partners. We found that subjects gradually learned to discriminate trustworthy partners from untrustworthy ones based on how often their partners reciprocated the investment, which was indicated by their own investment decisions. Besides, electrophysiological data showed that the faces of the untrustworthy partners induced larger feedback negativity (FN amplitude than those of the trustworthy partners, but only in the late phase of the game. The ERP results corresponded with the behavioral pattern and revealed that the learned trustworthiness differentiation was coded by the cue-elicited FN component. Consistent with previous research, our findings suggest that the anterior cue-elicited FN reflects the reputation appraisal and tracks the reputation learning process in social interactions.

Functional analysis of rice HOMEOBOX4 (Oshox4) gene reveals a negative function in gibberellin responses.

Science.gov (United States)

Dai, Mingqiu; Hu, Yongfeng; Ma, Qian; Zhao, Yu; Zhou, Dao-Xiu

2008-02-01

The homeodomain-leucine zipper (HD-Zip) putative transcription factor genes are divided into 4 families. In this work, we studied the function of a rice HD-Zip I gene, H OME O BO X4 (Oshox4). Oshox4 transcripts were detected in leaf and floral organ primordia but excluded from the shoot apical meristem and the protein was nuclear localized. Over-expression of Oshox4 in rice induced a semi-dwarf phenotype that could not be complemented by applied GA3. The over-expression plants accumulated elevated levels of bioactive GA, while the GA catabolic gene GA2ox3 was upregulated in the transgenic plants. In addition, over-expression of Oshox4 blocked GA-dependent alpha-amylase production. However, down-regulation of Oshox4 in RNAi transgenic plants induced no phenotypic alteration. Interestingly, the expression of YAB1 that is involved in the negative feedback regulation of the GA biosynthesis was upregulated in the Oshox4 over-expressing plants. One-hybrid assays showed that Oshox4 could interact with YAB1 promoter in yeast. In addition, Oshox4 expression was upregulated by GA. These data together suggest that Oshox4 may be involved in the negative regulation of GA signalling and may play a role to fine tune GA responses in rice.

A modular positive feedback-based gene amplifier

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Bhalerao Kaustubh D

2010-02-01

Full Text Available Abstract Background Positive feedback is a common mechanism used in the regulation of many gene circuits as it can amplify the response to inducers and also generate binary outputs and hysteresis. In the context of electrical circuit design, positive feedback is often considered in the design of amplifiers. Similar approaches, therefore, may be used for the design of amplifiers in synthetic gene circuits with applications, for example, in cell-based sensors. Results We developed a modular positive feedback circuit that can function as a genetic signal amplifier, heightening the sensitivity to inducer signals as well as increasing maximum expression levels without the need for an external cofactor. The design utilizes a constitutively active, autoinducer-independent variant of the quorum-sensing regulator LuxR. We experimentally tested the ability of the positive feedback module to separately amplify the output of a one-component tetracycline sensor and a two-component aspartate sensor. In each case, the positive feedback module amplified the response to the respective inducers, both with regards to the dynamic range and sensitivity. Conclusions The advantage of our design is that the actual feedback mechanism depends only on a single gene and does not require any other modulation. Furthermore, this circuit can amplify any transcriptional signal, not just one encoded within the circuit or tuned by an external inducer. As our design is modular, it can potentially be used as a component in the design of more complex synthetic gene circuits.

Students’ expectations of feedback given on draft writing

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Zach Simpson

2011-09-01

Full Text Available Academic writing is the primary means of assessing university students and feedback (oral or written responses on writing can contribute significantly to student learning and success (Ferris, 2003; Hyland & Hyland, 2006. This study explores students’ expectations of feedback on draft writing. The research design was two-pronged. The initial quantitative aspect employed a questionnaire which students completed after receiving feedback from Writing Centre consultants who aim to give developmental feedback. A subsequent phase involved focus groups with volunteer students. This mixed methods design allowed for greater depth of understanding as the qualitative findings extended the quantitative results. The study concludes that students expect feedback to be understandable, encouraging and to focus on both positive and negative aspects of their writing. Importantly, students expect feedback to ‘unpack’ the conventions of academic literacy while still encouraging independence and originality.

The Feedback-Related Negativity and the P300 Brain Potential Are Sensitive to Price Expectation Violations in a Virtual Shopping Task

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Schaefer, Alexandre; Buratto, Luciano G.; Goto, Nobuhiko; Brotherhood, Emilie V.

2016-01-01

A large body of evidence shows that buying behaviour is strongly determined by consumers’ price expectations and the extent to which real prices violate these expectations. Despite the importance of this phenomenon, little is known regarding its neural mechanisms. Here we show that two patterns of electrical brain activity known to index prediction errors–the Feedback-Related Negativity (FRN) and the feedback-related P300 –were sensitive to price offers that were cheaper than participants’ expectations. In addition, we also found that FRN amplitude time-locked to price offers predicted whether a product would be subsequently purchased or not, and further analyses suggest that this result was driven by the sensitivity of the FRN to positive price expectation violations. This finding strongly suggests that ensembles of neurons coding positive prediction errors play a critical role in real-life consumer behaviour. Further, these findings indicate that theoretical models based on the notion of prediction error, such as the Reinforcement Learning Theory, can provide a neurobiologically grounded account of consumer behavior. PMID:27658301

The Feedback-Related Negativity and the P300 Brain Potential Are Sensitive to Price Expectation Violations in a Virtual Shopping Task.

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Schaefer, Alexandre; Buratto, Luciano G; Goto, Nobuhiko; Brotherhood, Emilie V

A large body of evidence shows that buying behaviour is strongly determined by consumers' price expectations and the extent to which real prices violate these expectations. Despite the importance of this phenomenon, little is known regarding its neural mechanisms. Here we show that two patterns of electrical brain activity known to index prediction errors-the Feedback-Related Negativity (FRN) and the feedback-related P300 -were sensitive to price offers that were cheaper than participants' expectations. In addition, we also found that FRN amplitude time-locked to price offers predicted whether a product would be subsequently purchased or not, and further analyses suggest that this result was driven by the sensitivity of the FRN to positive price expectation violations. This finding strongly suggests that ensembles of neurons coding positive prediction errors play a critical role in real-life consumer behaviour. Further, these findings indicate that theoretical models based on the notion of prediction error, such as the Reinforcement Learning Theory, can provide a neurobiologically grounded account of consumer behavior.

bHLH003, bHLH013 and bHLH017 are new targets of JAZ repressors negatively regulating JA responses.

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Sandra Fonseca

Full Text Available Cell reprogramming in response to jasmonates requires a tight control of transcription that is achieved by the activity of JA-related transcription factors (TFs. Among them, MYC2, MYC3 and MYC4 have been described as activators of JA responses. Here we characterized the function of bHLH003, bHLH013 and bHLH017 that conform a phylogenetic clade closely related to MYC2, MYC3 and MYC4. We found that these bHLHs form homo- and heterodimers and also interact with JAZ repressors in vitro and in vivo. Phenotypic analysis of JA-regulated processes, including root and rosette growth, anthocyanin accumulation, chlorophyll loss and resistance to Pseudomonas syringae, on mutants and overexpression lines, suggested that these bHLHs are repressors of JA responses. bHLH003, bHLH013 and bHLH017 are mainly nuclear proteins and bind DNA with similar specificity to that of MYC2, MYC3 and MYC4, but lack a conserved activation domain, suggesting that repression is achieved by competition for the same cis-regulatory elements. Moreover, expression of bHLH017 is induced by JA and depends on MYC2, suggesting a negative feed-back regulation of the activity of positive JA-related TFs. Our results suggest that the competition between positive and negative TFs determines the output of JA-dependent transcriptional activation.

The interplay between feedback-related negativity and individual differences in altruistic punishment: An EEG study.

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Mothes, Hendrik; Enge, Sören; Strobel, Alexander

2016-04-01

To date, the interplay betwexen neurophysiological and individual difference factors in altruistic punishment has been little understood. To examine this issue, 45 individuals participated in a Dictator Game with punishment option while the feedback-related negativity (FRN) was derived from the electroencephalogram (EEG). Unlike previous EEG studies on the Dictator Game, we introduced a third party condition to study the effect of fairness norm violations in addition to employing a first person perspective. For the first time, we also examined the role of individual differences, specifically fairness concerns, positive/negative affectivity, and altruism/empathy as well as recipients' financial situation during altruistic punishment. The main results show that FRN amplitudes were more pronounced for unfair than for fair assignments in both the first person and third party perspectives. These findings suggest that FRN amplitudes are sensitive to fairness norm violations and play a crucial role in the recipients' evaluation of dictator assignments. With respect to individual difference factors, recipients' current financial situation affected the FRN fairness effect in the first person perspective, indicating that when being directly affected by the assignments, more affluent participants experienced stronger violations of expectations in altruistic punishment decisions. Regarding individual differences in trait empathy, in the third party condition FRN amplitudes were more pronounced for those who scored lower in empathy. This may suggest empathy as another motive in third party punishment. Independent of the perspective taken, higher positive affect was associated with more punishment behavior, suggesting that positive emotions may play an important role in restoring violated fairness norms.

Positive Feedback of NDT80 Expression Ensures Irreversible Meiotic Commitment in Budding Yeast

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Tsuchiya, Dai; Yang, Yang; Lacefield, Soni

2014-01-01

In budding yeast, meiotic commitment is the irreversible continuation of the developmental path of meiosis. After reaching meiotic commitment, cells finish meiosis and gametogenesis, even in the absence of the meiosis-inducing signal. In contrast, if the meiosis-inducing signal is removed and the mitosis-inducing signal is provided prior to reaching meiotic commitment, cells exit meiosis and return to mitosis. Previous work has shown that cells commit to meiosis after prophase I but before entering the meiotic divisions. Since the Ndt80 transcription factor induces expression of middle meiosis genes necessary for the meiotic divisions, we examined the role of the NDT80 transcriptional network in meiotic commitment. Using a microfluidic approach to analyze single cells, we found that cells commit to meiosis in prometaphase I, after the induction of the Ndt80-dependent genes. Our results showed that high-level expression of NDT80 is important for the timing and irreversibility of meiotic commitment. A modest reduction in NDT80 levels delayed meiotic commitment based on meiotic stages, although the timing of each meiotic stage was similar to that of wildtype cells. A further reduction of NDT80 resulted in the surprising finding of inappropriately uncommitted cells: withdrawal of the meiosis-inducing signal and addition of the mitosis-inducing signal to cells at stages beyond metaphase I caused return to mitosis, leading to multi-nucleate cells. Since Ndt80 enhances its own transcription through positive feedback, we tested whether positive feedback ensured the irreversibility of meiotic commitment. Ablating positive feedback in NDT80 expression resulted in a complete loss of meiotic commitment. These findings suggest that irreversibility of meiotic commitment is a consequence of the NDT80 transcriptional positive feedback loop, which provides the high-level of Ndt80 required for the developmental switch of meiotic commitment. These results also illustrate the

Post-transcriptional control of the mammalian circadian clock: implications for health and disease.

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Preußner, Marco; Heyd, Florian

2016-06-01

Many aspects of human physiology and behavior display rhythmicity with a period of approximately 24 h. Rhythmic changes are controlled by an endogenous time keeper, the circadian clock, and include sleep-wake cycles, physical and mental performance capability, blood pressure, and body temperature. Consequently, many diseases, such as metabolic, sleep, autoimmune and mental disorders and cancer, are connected to the circadian rhythm. The development of therapies that take circadian biology into account is thus a promising strategy to improve treatments of diverse disorders, ranging from allergic syndromes to cancer. Circadian alteration of body functions and behavior are, at the molecular level, controlled and mediated by widespread changes in gene expression that happen in anticipation of predictably changing requirements during the day. At the core of the molecular clockwork is a well-studied transcription-translation negative feedback loop. However, evidence is emerging that additional post-transcriptional, RNA-based mechanisms are required to maintain proper clock function. Here, we will discuss recent work implicating regulated mRNA stability, translation and alternative splicing in the control of the mammalian circadian clock, and its role in health and disease.

Global Stability in Dynamical Systems with Multiple Feedback Mechanisms

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Andersen, Morten; Vinther, Frank; Ottesen, Johnny T.

2016-01-01

A class of n-dimensional ODEs with up to n feedbacks from the n’th variable is analysed. The feedbacks are represented by non-specific, bounded, non-negative C1 functions. The main result is the formulation and proof of an easily applicable criterion for existence of a globally stable fixed point...

An integrative model linking feedback environment and organizational citizenship behavior.

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Peng, Jei-Chen; Chiu, Su-Fen

2010-01-01

Past empirical evidence has suggested that a positive supervisor feedback environment may enhance employees' organizational citizenship behavior (OCB). In this study, we aim to extend previous research by proposing and testing an integrative model that examines the mediating processes underlying the relationship between supervisor feedback environment and employee OCB. Data were collected from 259 subordinate-supervisor dyads across a variety of organizations in Taiwan. We used structural equation modeling to test our hypotheses. The results demonstrated that supervisor feedback environment influenced employees' OCB indirectly through (1) both positive affective-cognition and positive attitude (i.e., person-organization fit and organizational commitment), and (2) both negative affective-cognition and negative attitude (i.e., role stressors and job burnout). Theoretical and practical implications are discussed.

Quantifying the relative contributions of divisive and subtractive feedback to rhythm generation.

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Joël Tabak

2011-04-01

Full Text Available Biological systems are characterized by a high number of interacting components. Determining the role of each component is difficult, addressed here in the context of biological oscillations. Rhythmic behavior can result from the interplay of positive feedback that promotes bistability between high and low activity, and slow negative feedback that switches the system between the high and low activity states. Many biological oscillators include two types of negative feedback processes: divisive (decreases the gain of the positive feedback loop and subtractive (increases the input threshold that both contribute to slowly move the system between the high- and low-activity states. Can we determine the relative contribution of each type of negative feedback process to the rhythmic activity? Does one dominate? Do they control the active and silent phase equally? To answer these questions we use a neural network model with excitatory coupling, regulated by synaptic depression (divisive and cellular adaptation (subtractive feedback. We first attempt to apply standard experimental methodologies: either passive observation to correlate the variations of a variable of interest to system behavior, or deletion of a component to establish whether a component is critical for the system. We find that these two strategies can lead to contradictory conclusions, and at best their interpretive power is limited. We instead develop a computational measure of the contribution of a process, by evaluating the sensitivity of the active (high activity and silent (low activity phase durations to the time constant of the process. The measure shows that both processes control the active phase, in proportion to their speed and relative weight. However, only the subtractive process plays a major role in setting the duration of the silent phase. This computational method can be used to analyze the role of negative feedback processes in a wide range of biological rhythms.

Neuroticism and responsiveness to error feedback: adaptive self-regulation versus affective reactivity.

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Robinson, Michael D; Moeller, Sara K; Fetterman, Adam K

2010-10-01

Responsiveness to negative feedback has been seen as functional by those who emphasize the value of reflecting on such feedback in self-regulating problematic behaviors. On the other hand, the very same responsiveness has been viewed as dysfunctional by its link to punishment sensitivity and reactivity. The present 4 studies, involving 203 undergraduate participants, sought to reconcile such discrepant views in the context of the trait of neuroticism. In cognitive tasks, individuals were given error feedback when they made mistakes. It was found that greater tendencies to slow down following error feedback were associated with higher levels of accuracy at low levels of neuroticism but lower levels of accuracy at high levels of neuroticism. Individual differences in neuroticism thus appear crucial in understanding whether behavioral alterations following negative feedback reflect proactive versus reactive mechanisms and processes. Implications for understanding the processing basis of neuroticism and adaptive self-regulation are discussed.

A RNA transcript (Heg) in mononuclear cells is negatively correlated with CD14 mRNA and TSH receptor autoantibodies

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Habekost, G.; Bratholm, P.; Christensen, Niels Juel

2008-01-01

of the poly A(-) transcript (designated Heg) in mononuclear cells was correlated with CD14 mRNA in normal subjects and with CD14 mRNA and TSH receptor autoantibodies in patients with acute and untreated Graves' disease. mRNA was expressed in amol/mu g DNA. The main study groups were: (i) normal subjects; (ii......) patients with early and untreated Graves' disease; and (iii) patients with Graves' disease studied after treatment. In 18 normal subjects and in 20 patients with treated Graves' disease CD14 mRNA was negatively correlated with Heg (P Graves' disease Heg and thyroid...

A Proposed Conceptual Framework and Investigation of Upward Feedback Receptivity in Medical Education.

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Kost, Amanda; Combs, Heidi; Smith, Sherilyn; Klein, Eileen; Kritek, Patricia; Robins, Lynne; Cianciolo, Anna T; Butani, Lavjay; Gigante, Joseph; Ramani, Subha

2015-01-01

WGEA 2015 CONFERENCE ABSTRACT (EDITED). Faculty Perceptions of Receiving Feedback From Third-Year Clerkship Students. Amanda Kost, Heidi Combs, Sherilyn Smith, Eileen Klein, Patricia Kritek, and Lynne Robins. PHENOMENON: In addition to giving feedback to 3rd-year clerkship students, some clerkship instructors receive feedback, requested or spontaneous, from students prior to the clerkship's end. The concept of bidirectional feedback is appealing as a means of fostering a culture of respectful communication and improvement. However, little is known about how teachers perceive this feedback in practice or how it impacts the learning environment. We performed 24 semistructured 30-minute interviews with 3 to 7 attending physician faculty members each in Pediatrics, Internal Medicine, Family Medicine, Surgery, Psychiatry, and Obstetrics and Gynecology who taught in 3rd-year required clerkships during the 2012-2013 academic year. Questions probed teachers' experience with and attitudes toward receiving student feedback. Prompts were used to elicit stories and obtain participant demographics. Interviews were audio-recorded, transcribed, and entered into Dedoose for qualitative analysis. Researchers read transcripts holistically for meaning, designed a coding template, and then independently coded each transcript. A constant comparative approach and regular meetings were used to ensure consistent coding between research team members. Participants ranged in age from 37 to 74, with 5 to 35 years of teaching experience. Seventy-one percent were male, and 83% identified as White. In our preliminary analysis, our informants reported a range of experience in receiving student feedback prior to the end of a clerkship, varying from no experience to having developed mechanisms to regularly request specific feedback about their programs. Most expressed openness to actively soliciting and receiving student feedback on their teaching during the clerkship although many questioned

How does feedback in mini-CEX affect students' learning response?

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Sudarso, Sulistiawati; Rahayu, Gandes Retno; Suhoyo, Yoyo

2016-12-19

This study was aimed to explore students' learning response toward feedback during mini-CEX encounter. This study used a phenomenological approach to identify the students' experiences toward feedback during mini-CEX encounter. Data was collected using Focus Group Discussion (FGD) for all students who were in their final week of clerkship in the internal medicine rotation. There were 4 FGD groups (6 students for each group). All FGD were audio-taped and transcribed verbatim. The FGD transcripts were analyzed thematically and managed using Atlas-ti (version 7.0). Feedback content and the way of providing feedback on mini-CEX stimulated students' internal process, including self-reflection, emotional response, and motivation. These internal processes encouraged the students to take action or do a follow-up on the feedback to improve their learning process. In addition, there was also an external factor, namely consequences, which also influenced the students' reaction to the follow-up on feedback. In the end, this action caused several learning effects that resulted in the students' increased self-efficacy, attitude, knowledge and clinical skill. Feedback content and the way of providing feedback on mini-CEX stimulates the students' internal processes to do a follow-up on feedback. However, another external factor also affects the students' decision on the follow-up actions. The follow-ups result in various learning effects on the students. Feedback given along with summative assessment enhances learning effects on students, as well. It is suggested that supervisors of clinical education are prepared to comprehend every factor influencing feedback on mini CEX to improve the students' learning response.

Gene Expression Profiling Reveals a Massive, Aneuploidy-Dependent Transcriptional Deregulation and Distinct Differences between Lymph Node–Negative and Lymph Node–Positive Colon Carcinomas

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Grade, Marian; Hörmann, Patrick; Becker, Sandra; Hummon, Amanda B.; Wangsa, Danny; Varma, Sudhir; Simon, Richard; Liersch, Torsten; Becker, Heinz; Difilippantonio, Michael J.; Ghadimi, B. Michael; Ried, Thomas

2016-01-01

To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P 5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node–negative and lymph node–positive tumors (P deregulated genes were validated using quantitative real-time reverse transcription-PCR in >40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/β-catenin signaling cascade, suggesting similar pathogenic pathways. PMID:17210682

Asymmetric positive feedback loops reliably control biological responses.

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Ratushny, Alexander V; Saleem, Ramsey A; Sitko, Katherine; Ramsey, Stephen A; Aitchison, John D

2012-04-24

Positive feedback is a common mechanism enabling biological systems to respond to stimuli in a switch-like manner. Such systems are often characterized by the requisite formation of a heterodimer where only one of the pair is subject to feedback. This ASymmetric Self-UpREgulation (ASSURE) motif is central to many biological systems, including cholesterol homeostasis (LXRα/RXRα), adipocyte differentiation (PPARγ/RXRα), development and differentiation (RAR/RXR), myogenesis (MyoD/E12) and cellular antiviral defense (IRF3/IRF7). To understand why this motif is so prevalent, we examined its properties in an evolutionarily conserved transcriptional regulatory network in yeast (Oaf1p/Pip2p). We demonstrate that the asymmetry in positive feedback confers a competitive advantage and allows the system to robustly increase its responsiveness while precisely tuning the response to a consistent level in the presence of varying stimuli. This study reveals evolutionary advantages for the ASSURE motif, and mechanisms for control, that are relevant to pharmacologic intervention and synthetic biology applications.

Negative feedback loop of bone resorption by NFATc1-dependent induction of Cadm1.

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Shinya Nakamura

Full Text Available Trimethylation of histone H3 lysine 4 and lysine 27 (H3K4me3 and H3K27me3 at gene promoter regions critically regulates gene expression. Key developmental genes tend to exhibit changes in histone modification patterns from the H3K4me3/H3K27me3 bivalent pattern to the H3K4me3 monovalent pattern. Using comprehensive chromatin immunoprecipitation followed by sequencing in bone marrow-derived macrophages (BMMs and mature osteoclasts, we found that cell surface adhesion molecule 1 (Cadm1 is a direct target of nuclear factor of activated T cells 1 (NFATc1 and exhibits a bivalent histone pattern in BMMs and a monovalent pattern in osteoclasts. Cadm1 expression was upregulated in BMMs by receptor activator of nuclear factor kappa B ligand (RANKL, and blocked by a calcineurin/NFATc1 inhibitor, FK506. Cadm1-deficient mice exhibited significantly reduced bone mass compared with wild-type mice, which was due to the increased osteoclast differentiation, survival and bone-resorbing activity in Cadm1-deficient osteoclasts. These results suggest that Cadm1 is a direct target of NFATc1, which is induced by RANKL through epigenetic modification, and regulates osteoclastic bone resorption in a negative feedback manner.

Inhibitory and toxic effects of extracellular self-DNA in litter: a mechanism for negative plant-soil feedbacks?

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Mazzoleni, Stefano; Bonanomi, Giuliano; Incerti, Guido; Chiusano, Maria Luisa; Termolino, Pasquale; Mingo, Antonio; Senatore, Mauro; Giannino, Francesco; Cartenì, Fabrizio; Rietkerk, Max; Lanzotti, Virginia

2015-02-01

Plant-soil negative feedback (NF) is recognized as an important factor affecting plant communities. The objectives of this work were to assess the effects of litter phytotoxicity and autotoxicity on root proliferation, and to test the hypothesis that DNA is a driver of litter autotoxicity and plant-soil NF. The inhibitory effect of decomposed litter was studied in different bioassays. Litter biochemical changes were evaluated with nuclear magnetic resonance (NMR) spectroscopy. DNA accumulation in litter and soil was measured and DNA toxicity was assessed in laboratory experiments. Undecomposed litter caused nonspecific inhibition of root growth, while autotoxicity was produced by aged litter. The addition of activated carbon (AC) removed phytotoxicity, but was ineffective against autotoxicity. Phytotoxicity was related to known labile allelopathic compounds. Restricted (13) C NMR signals related to nucleic acids were the only ones negatively correlated with root growth on conspecific substrates. DNA accumulation was observed in both litter decomposition and soil history experiments. Extracted total DNA showed evident species-specific toxicity. Results indicate a general occurrence of litter autotoxicity related to the exposure to fragmented self-DNA. The evidence also suggests the involvement of accumulated extracellular DNA in plant-soil NF. Further studies are needed to further investigate this unexpected function of extracellular DNA at the ecosystem level and related cellular and molecular mechanisms. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Post-translational regulation enables robust p53 regulation.

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Shin, Yong-Jun; Chen, Kai-Yuan; Sayed, Ali H; Hencey, Brandon; Shen, Xiling

2013-08-30

The tumor suppressor protein p53 plays important roles in DNA damage repair, cell cycle arrest and apoptosis. Due to its critical functions, the level of p53 is tightly regulated by a negative feedback mechanism to increase its tolerance towards fluctuations and disturbances. Interestingly, the p53 level is controlled by post-translational regulation rather than transcriptional regulation in this feedback mechanism. We analyzed the dynamics of this feedback to understand whether post-translational regulation provides any advantages over transcriptional regulation in regard to disturbance rejection. When a disturbance happens, even though negative feedback reduces the steady-state error, it can cause a system to become less stable and transiently overshoots, which may erroneously trigger downstream reactions. Therefore, the system needs to balance the trade-off between steady-state and transient errors. Feedback control and adaptive estimation theories revealed that post-translational regulation achieves a better trade-off than transcriptional regulation, contributing to a more steady level of p53 under the influence of noise and disturbances. Furthermore, post-translational regulation enables cells to respond more promptly to stress conditions with consistent amplitude. However, for better disturbance rejection, the p53- Mdm2 negative feedback has to pay a price of higher stochastic noise. Our analyses suggest that the p53-Mdm2 feedback favors regulatory mechanisms that provide the optimal trade-offs for dynamic control.

Transcription factor trapping by RNA in gene regulatory elements.

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Sigova, Alla A; Abraham, Brian J; Ji, Xiong; Molinie, Benoit; Hannett, Nancy M; Guo, Yang Eric; Jangi, Mohini; Giallourakis, Cosmas C; Sharp, Phillip A; Young, Richard A

2015-11-20

Transcription factors (TFs) bind specific sequences in promoter-proximal and -distal DNA elements to regulate gene transcription. RNA is transcribed from both of these DNA elements, and some DNA binding TFs bind RNA. Hence, RNA transcribed from regulatory elements may contribute to stable TF occupancy at these sites. We show that the ubiquitously expressed TF Yin-Yang 1 (YY1) binds to both gene regulatory elements and their associated RNA species across the entire genome. Reduced transcription of regulatory elements diminishes YY1 occupancy, whereas artificial tethering of RNA enhances YY1 occupancy at these elements. We propose that RNA makes a modest but important contribution to the maintenance of certain TFs at gene regulatory elements and suggest that transcription of regulatory elements produces a positive-feedback loop that contributes to the stability of gene expression programs. Copyright © 2015, American Association for the Advancement of Science.

The Greenhouse Effect and Climate Feedbacks

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Covey, C.; Haberle, R. M.; McKay, C. P.; Titov, D. V.

This chapter reviews the theory of the greenhouse effect and climate feedback. It also compares the theory with observations, using examples taken from all four known terrestrial worlds with substantial atmospheres: Venus, Earth, Mars, and Titan. The greenhouse effect traps infrared radiation in the atmosphere, thereby increasing surface temperature. It is one of many factors that affect a world's climate. (Others include solar luminosity and the atmospheric scattering and absorption of solar radiation.) A change in these factors — defined as climate forcing — may change the climate in a way that brings other processes — defined as feedbacks — into play. For example, when Earth's atmospheric carbon dioxide increases, warming the surface, the water vapor content of the atmosphere increases. This is a positive feedback on global warming because water vapor is itself a potent greenhouse gas. Many positive and negative feedback processes are significant in determining Earth's climate, and probably the climates of our terrestrial neighbors.

Perioperative feedback in surgical training: A systematic review.

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McKendy, Katherine M; Watanabe, Yusuke; Lee, Lawrence; Bilgic, Elif; Enani, Ghada; Feldman, Liane S; Fried, Gerald M; Vassiliou, Melina C

2017-07-01

Changes in surgical training have raised concerns about residents' operative exposure and preparedness for independent practice. One way of addressing this concern is by optimizing teaching and feedback in the operating room (OR). The objective of this study was to perform a systematic review on perioperative teaching and feedback. A systematic literature search identified articles from 1994 to 2014 that addressed teaching, feedback, guidance, or debriefing in the perioperative period. Data was extracted according to ENTREQ guidelines, and a qualitative analysis was performed. Thematic analysis of the 26 included studies identified four major topics. Observation of teaching behaviors in the OR described current teaching practices. Identification of effective teaching strategies analyzed teaching behaviors, differentiating positive and negative teaching strategies. Perceptions of teaching behaviors described resident and attending satisfaction with teaching in the OR. Finally models for delivering structured feedback cited examples of feedback strategies and measured their effectiveness. This study provides an overview of perioperative teaching and feedback for surgical trainees and identifies a need for improved quality and quantity of structured feedback. Copyright © 2016 Elsevier Inc. All rights reserved.

Contributions of Different Cloud Types to Feedbacks and Rapid Adjustments in CMIP5*

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Zelinka, Mark D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Program for Climate Model Diagnosis and Intercomparison; Klein, Stephen A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Program for Climate Model Diagnosis and Intercomparison; Taylor, Karl E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Program for Climate Model Diagnosis and Intercomparison; Andrews, Timothy [Met Office Hadley Center, Exeter (United Kingdom); Webb, Mark J. [Met Office Hadley Center, Exeter (United Kingdom); Gregory, Jonathan M. [Univ. of Reading, Exeter (United Kingdom). National Center for Atmospheric Science; Forster, Piers M. [Univ. of Leeds (United Kingdom)

2013-07-01

When using five climate model simulations of the response to an abrupt quadrupling of CO₂, the authors perform the first simultaneous model intercomparison of cloud feedbacks and rapid radiative adjustments with cloud masking effects removed, partitioned among changes in cloud types and gross cloud properties. After CO₂ quadrupling, clouds exhibit a rapid reduction in fractional coverage, cloud-top pressure, and optical depth, with each contributing equally to a 1.1 W m^-2 net cloud radiative adjustment, primarily from shortwave radiation. Rapid reductions in midlevel clouds and optically thick clouds are important in reducing planetary albedo in every model. As the planet warms, clouds become fewer, higher, and thicker, and global mean net cloud feedback is positive in all but one model and results primarily from increased trapping of longwave radiation. As was true for earlier models, high cloud changes are the largest contributor to intermodel spread in longwave and shortwave cloud feedbacks, but low cloud changes are the largest contributor to the mean and spread in net cloud feedback. The importance of the negative optical depth feedback relative to the amount feedback at high latitudes is even more marked than in earlier models. Furthermore, the authors show that the negative longwave cloud adjustment inferred in previous studies is primarily caused by a 1.3 W m^-2 cloud masking of CO₂ forcing. Properly accounting for cloud masking increases net cloud feedback by 0.3 W m^-2 K^-1, whereas accounting for rapid adjustments reduces by 0.14 W m^-2 K^-1 the ensemble mean net cloud feedback through a combination of smaller positive cloud amount and altitude feedbacks and larger negative optical depth feedbacks.

Effects of feedback reliability on feedback-related brain activity: A feedback valuation account.

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Ernst, Benjamin; Steinhauser, Marco

2018-04-06

Adaptive decision making relies on learning from feedback. Because feedback sometimes can be misleading, optimal learning requires that knowledge about the feedback's reliability be utilized to adjust feedback processing. Although previous research has shown that feedback reliability indeed influences feedback processing, the underlying mechanisms through which this is accomplished remain unclear. Here we propose that feedback processing is adjusted by the adaptive, top-down valuation of feedback. We assume that unreliable feedback is devalued relative to reliable feedback, thus reducing the reward prediction errors that underlie feedback-related brain activity and learning. A crucial prediction of this account is that the effects of feedback reliability are susceptible to contrast effects. That is, the effects of feedback reliability should be enhanced when both reliable and unreliable feedback are experienced within the same context, as compared to when only one level of feedback reliability is experienced. To evaluate this prediction, we measured the event-related potentials elicited by feedback in two experiments in which feedback reliability was varied either within or between blocks. We found that the fronto-central valence effect, a correlate of reward prediction errors during reinforcement learning, was reduced for unreliable feedback. But this result was obtained only when feedback reliability was varied within blocks, thus indicating a contrast effect. This suggests that the adaptive valuation of feedback is one mechanism underlying the effects of feedback reliability on feedback processing.

When compliments don't hit but critiques do: an fMRI study into self-esteem and self-knowledge in processing social feedback.

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van Schie, C C; Chiu, C D; Rombouts, S A R B; Heiser, W J; Elzinga, B M

2018-02-27

The way we view ourselves may play an important role in our responses to interpersonal interactions. In this study, we investigate how feedback valence, consistency of feedback with self-knowledge and global self-esteem influence affective and neural responses to social feedback. Participants (N = 46) with a high range of self-esteem levels performed the social feedback task in an MRI scanner. Negative, intermediate and positive feedback was provided, supposedly by another person based on a personal interview. Participants rated their mood and applicability of feedback to the self. Analyses on trial basis on neural and affective responses are used to incorporate applicability of individual feedback words. Lower self-esteem related to low mood especially after receiving non-applicable negative feedback. Higher self-esteem related to increased PCC and precuneus activation (i.e., self-referential processing) for applicable negative feedback. Lower self-esteem related to decreased mPFC, insula, ACC and PCC activation (i.e, self-referential processing) during positive feedback and decreased TPJ activation (i.e., other referential processing) for applicable positive feedback. Self-esteem and consistency of feedback with self-knowledge appear to guide our affective and neural responses to social feedback. This may be highly relevant for the interpersonal problems that individuals face with low self-esteem and negative self-views.

Self-Verification Strivings in Children Holding Negative Self-Views: The Mitigating Effects of a Preceding Success Experience.

Science.gov (United States)

Reijntjes, Albert; Thomaes, Sander; Kamphuis, Jan Henk; de Castro, Bram Orobio; Telch, Michael J

2010-12-01

Research among adults has consistently shown that people holding negative self-views prefer negative over positive feedback. The present study tested the hypothesis that this preference is less robust among pre-adolescents, such that it will be mitigated by a preceding positive event. Pre-adolescents (n = 75) holding positive or negative global self-esteem were randomized to a favorable or unfavorable peer evaluation outcome. Next, preferences for positive versus negative feedback were assessed using an unobtrusive behavioral viewing time measure. As expected, results showed that after being faced with the success outcome children holding negative self-views were as likely as their peers holding positive self-views to display a significant preference for positive feedback. In contrast, children holding negative self-views displayed a stronger preference for negative feedback after being faced with the unfavorable outcome that matched their pre-existing self-views.

Study on Air-cooled Self-humidifying PEMFC Control Method Based on Segmented Predict Negative Feedback Control

International Nuclear Information System (INIS)

Zhiyu, You; Tao, Xu; Zhixiang, Liu; Yun, Peng; Weirong, Cheng

2014-01-01

In order to obtain the optimal output performance of the air-cooled self-humidifying proton exchange membrane fuel cell (PEMFC), the operating temperature, the air flow, purge interval and some other parameters must be controlled strictly. As a key factor, the operating temperature mainly determines the optimal output performance of the fuel cell. However, some intrinsic issues such as long adjusting time, over-shoot still exist inevitably for the traditional PID temperature-controlled method in circumstances of the load variation. Consequently, output performance of PEMFC decreases because the operating temperature of the fuel cell fails to reach, and the corresponding lifetime of PEMFC is also reduced. In this study, a segmented predict negative feedback control method, based on the advance proportional control one, is proposed and verified by experiments to overcome the shortcomings of PID temperature control. The results demonstrate that the optimal output performance of PEMFC can be realized by utilizing the proposed method for temperature control due to its excellent properties, simple controlling and small over-shoot

How does feedback in mini-CEX affect students’ learning response?

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Rahayu, Gandes Retno; Suhoyo, Yoyo

2016-01-01

Objective This study was aimed to explore students’ learning response toward feedback during mini-CEX encounter. Methods This study used a phenomenological approach to identify the students’ experiences toward feedback during mini-CEX encounter. Data was collected using Focus Group Discussion (FGD) for all students who were in their final week of clerkship in the internal medicine rotation. There were 4 FGD groups (6 students for each group). All FGD were audio-taped and transcribed verbatim. The FGD transcripts were analyzed thematically and managed using Atlas-ti (version 7.0). Results Feedback content and the way of providing feedback on mini-CEX stimulated students’ internal process, including self-reflection, emotional response, and motivation. These internal processes encouraged the students to take action or do a follow-up on the feedback to improve their learning process. In addition, there was also an external factor, namely consequences, which also influenced the students’ reaction to the follow-up on feedback. In the end, this action caused several learning effects that resulted in the students’ increased self-efficacy, attitude, knowledge and clinical skill. Conclusions Feedback content and the way of providing feedback on mini-CEX stimulates the students’ internal processes to do a follow-up on feedback. However, another external factor also affects the students’ decision on the follow-up actions. The follow-ups result in various learning effects on the students. Feedback given along with summative assessment enhances learning effects on students, as well. It is suggested that supervisors of clinical education are prepared to comprehend every factor influencing feedback on mini CEX to improve the students’ learning response. PMID:28008136

Memory for performance feedback :a test of three self- motivation theories

OpenAIRE

Donlin, Joanne Mac

1990-01-01

The current study tests the adequacy of three self-motive theories to predict recall of performance feedback, memory sensitivity, and ratings of perceived accuracy. Self-enhancement (Jones, 1973) predicts individuals are motivated to maintain their self-esteem. Individuals will therefore recall positive relative to negative feedback and will rate positive feedback as more accurate. Self-consistency theory (Swann, 1985) predicts individuals are motivated to maintain their self-conceptions. The...

microProtein Prediction Program (miP3) : A Software for Predicting microProteins and Their Target Transcription Factors

NARCIS (Netherlands)

de Klein, Niek; Magnani, Enrico; Banf, Michael; Rhee, Seung Yon

2015-01-01

An emerging concept in transcriptional regulation is that a class of truncated transcription factors (TFs), called microProteins (miPs), engages in protein-protein interactions with TF complexes and provides feedback controls. A handful of miP examples have been described in the literature but the

When compliments do not hit but critiques do: an fMRI study into self-esteem and self-knowledge in processing social feedback

Science.gov (United States)

van Schie, Charlotte C; Chiu, Chui-De; Rombouts, Serge A R B; Heiser, Willem J; Elzinga, Bernet M

2018-01-01

Abstract The way we view ourselves may play an important role in our responses to interpersonal interactions. In this study, we investigate how feedback valence, consistency of feedback with self-knowledge and global self-esteem influence affective and neural responses to social feedback. Participants (N = 46) with a high range of self-esteem levels performed the social feedback task in an MRI scanner. Negative, intermediate and positive feedback was provided, supposedly by another person based on a personal interview. Participants rated their mood and applicability of feedback to the self. Analyses on trial basis on neural and affective responses are used to incorporate applicability of individual feedback words. Lower self-esteem related to low mood especially after receiving non-applicable negative feedback. Higher self-esteem related to increased posterior cingulate cortex and precuneus activation (i.e. self-referential processing) for applicable negative feedback. Lower self-esteem related to decreased medial prefrontal cortex, insula, anterior cingulate cortex and posterior cingulate cortex activation (i.e. self-referential processing) during positive feedback and decreased temporoparietal junction activation (i.e. other referential processing) for applicable positive feedback. Self-esteem and consistency of feedback with self-knowledge appear to guide our affective and neural responses to social feedback. This may be highly relevant for the interpersonal problems that individuals face with low self-esteem and negative self-views. PMID:29490088

Polarized Th1 and Th2 cells are less responsive to negative feedback by receptors coupled to the AC/cAMP system compared to freshly isolated T cells

NARCIS (Netherlands)

Heijink, Irene H; Vellenga, Edo; Borger, Peter; Postma, Dirkje S; Monchy, Jan G R de; Kauffman, Henk F

1 The adenylyl cyclase (AC)/cyclic adenosine monophosphate (cAMP) system is known to negatively regulate transcriptional activity of T cells, thereby possibly modulating T-cell-mediated responses at the sites of inflammation. Effects of cAMP have been widely studied in freshly isolated T cells and

Effects of Semantic Context and Feedback on Perceptual Learning of Speech Processed through an Acoustic Simulation of a Cochlear Implant

Science.gov (United States)

Loebach, Jeremy L.; Pisoni, David B.; Svirsky, Mario A.

2010-01-01

The effect of feedback and materials on perceptual learning was examined in listeners with normal hearing who were exposed to cochlear implant simulations. Generalization was most robust when feedback paired the spectrally degraded sentences with their written transcriptions, promoting mapping between the degraded signal and its acoustic-phonetic…

FOXP3 Transcription Factor: A Candidate Marker for Susceptibility and Prognosis in Triple Negative Breast Cancer

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Leandra Fiori Lopes

2014-01-01

Full Text Available Triple negative breast cancer (TNBC is a relevant subgroup of neoplasia which presents negative phenotype of estrogen and progesterone receptors and has no overexpression of the human epidermal growth factor 2 (HER2. FOXP3 (forkhead transcription factor 3 is a marker of regulatory T cells (Tregs, whose expression may be increased in tumor cells. This study aimed to investigate a polymorphism (rs3761548 and the protein expression of FOXP3 for a possible involvement in TNBC susceptibility and prognosis. Genetic polymorphism was evaluated in 50 patients and in 115 controls by allele-specific PCR (polymerase chain reaction. Protein expression was evaluated in 38 patients by immunohistochemistry. It was observed a positive association for homozygous AA (OR = 3.78; 95% CI = 1.02–14.06 in relation to TNBC susceptibility. Most of the patients (83% showed a strong staining for FOXP3 protein in the tumor cells. In relation to FOXP3-positive infiltrate, 47% and 58% of patients had a moderate or intense intratumoral and peritumoral mononuclear infiltrate cells, respectively. Tumor size was positively correlated to intratumoral FOXP3-positive infiltrate (P=0.026. In conclusion, since FOXP3 was positively associated with TNBC susceptibility and prognosis, it seems to be a promising candidate for further investigation in larger TNBC samples.

Feedback coupling in dynamical systems

Science.gov (United States)

Trimper, Steffen; Zabrocki, Knud

2003-05-01

Different evolution models are considered with feedback-couplings. In particular, we study the Lotka-Volterra system under the influence of a cumulative term, the Ginzburg-Landau model with a convolution memory term and chemical rate equations with time delay. The memory leads to a modified dynamical behavior. In case of a positive coupling the generalized Lotka-Volterra system exhibits a maximum gain achieved after a finite time, but the population will die out in the long time limit. In the opposite case, the time evolution is terminated in a crash. Due to the nonlinear feedback coupling the two branches of a bistable model are controlled by the the strength and the sign of the memory. For a negative coupling the system is able to switch over between both branches of the stationary solution. The dynamics of the system is further controlled by the initial condition. The diffusion-limited reaction is likewise studied in case the reacting entities are not available simultaneously. Whereas for an external feedback the dynamics is altered, but the stationary solution remain unchanged, a self-organized internal feedback leads to a time persistent solution.

The challenge of giving written thesis feedback to nursing students.

Science.gov (United States)

Tuvesson, Hanna; Borglin, Gunilla

2014-11-01

Providing effective written feedback on nursing student's assignments can be a challenging task for any assessor. Additionally, as the student groups tend to become larger, written feedback is likely to gain an overall more prominent position than verbal feedback. Lack of formal training or regular discussion in the teaching faculty about the skill set needed to provide written feedback could negatively affect the students' learning abilities. In this brief paper, we discuss written feedback practices, whilst using the Bachelor of Science in Nursing thesis as an example. Our aim is to highlight the importance of an informed understanding of the impact written feedback can have on students. Creating awareness about this can facilitate the development of more strategic and successful written feedback strategies. We end by offering examples of some relatively simple strategies for improving this practice. Copyright © 2014 Elsevier Ltd. All rights reserved.

Appearance feedback in intimate relationships: the role of self-verification and self-enhancement.

Science.gov (United States)

Brown, Jennifer N; Stukas, Arthur A; Evans, Lynette

2013-01-01

To better understand how body image operates within the context of intimate relationships, we investigated women's responses to appearance feedback from an intimate partner. Participants (N=192) imagined receiving feedback from their partner that was either consistent with their own appearance self-view (i.e., self-verifying), more positive (i.e., self-enhancing), or less positive (i.e., devaluing), and then provided their affective and cognitive reactions. As expected, women's perceptions of their own appearance moderated their reactions. Women with more negative self-views felt happier with enhancing feedback, but thought that it meant their partner understood them less well. They also felt less happy when they received verifying feedback, but felt more understood by their partners. Thus, women with body image dissatisfaction may find themselves stuck in the "cognitive-affective crossfire" reacting ambivalently whether their partner enhances their appearance or confirms their negative self-views. Further examination of partners' actual feedback is needed. Copyright © 2012 Elsevier Ltd. All rights reserved.

A conceptual framework for regional feedbacks in a changing climate

Science.gov (United States)

Batlle Bayer, L.; van den Hurk, B. J. J. M.; Strengers, B.

2012-04-01

Terrestrial ecosystems and climate influence each other through biogeochemical (e.g. carbon cycle) and biogeophysical (e.g. albedo, water fluxes) processes. These interactions might be disturbed when a climate human-induced forcing takes place (e.g. deforestation); and the ecosystem responses to the climate system might amplify (positive feedback) or dampen (negative feedback) the initial forcing. Research on feedbacks has been mainly based on the carbon cycle at the global scale. However, biogeophysical feedbacks might have a great impact at the local or regional scale, which is the main focus of this article. A conceptual framework, with the major interactions and processes between terrestrial ecosystems and climate, is presented to further explore feedbacks at the regional level. Four hot spots with potential changes in land use/management and climate are selected: sub-Saharan Africa (SSA), Europe, the Amazon Basin and South and Southeast Asia. For each region, diverse climate human-induced forcings and feedbacks were identified based on relevant published literature. For Europe, the positive soil moisture-evapotranspiration (ET) is important for natural vegetation during a heat wave event, while the positive soil moisture-precipitation feedback plays a more important role for droughts in the Amazon region. Agricultural expansion in SSA will depend on the impacts of the changing climate on crop yields and the adopted agro-technologies. The adoption of irrigation in the commonly rainfed systems might turn the positive soil moisture- ET feedback into a negative one. In contrast, South and Southeast Asia might face water shortage in the future, and thus turning the soil moisture-ET feedback into a positive one. Further research is needed for the major processes that affect the ultimate sign of the feedbacks, as well as for the interactions, which effect remains uncertain, such as ET-precipitation interaction. In addition, socio-economic feedbacks need to be added

Children’s Feedback Preferences in Response to an Experimentally Manipulated Peer Evaluation Outcome: The Role of Depressive Symptoms

Science.gov (United States)

Dekovic, Maja; Vermande, Marjolijn; Telch, Michael J.

2007-01-01

The present study examined the linkage between pre-adolescent children’s depressive symptoms and their preferences for receiving positive vs. negative feedback subsequent to being faced with an experimentally manipulated peer evaluation outcome in real time. Participants (n = 142) ages 10 to 13, played a computer contest based on the television show Survivor and were randomized to either a peer rejection (i.e., receiving the lowest total ‘likeability’ score from a group of peer-judges), a peer success (i.e., receiving the highest score), or a control peer evaluation condition. Children’s self-reported feedback preferences were then assessed. Results revealed that participants assigned to the negative evaluation outcome, relative to either the success or the control outcome, showed a significantly higher subsequent preference for negatively tuned feedback. Contrary to previous work and predictions derived from self-verification theory, children higher in depressive symptoms were only more likely to prefer negative feedback in response to the negative peer evaluation outcome. These effects for depression were not accounted for by either state mood at baseline or mood change in response to the feedback manipulation. PMID:17279340

Social closeness and feedback modulate susceptibility to the framing effect.

Science.gov (United States)

Sip, Kamila E; Smith, David V; Porcelli, Anthony J; Kar, Kohitij; Delgado, Mauricio R

2015-01-01

Although we often seek social feedback (SFB) from others to help us make decisions, little is known about how SFB affects decisions under risk, particularly from a close peer. We conducted two experiments using an established framing task to probe how decision-making is modulated by SFB valence (positive, negative) and the level of closeness with feedback provider (friend, confederate). Participants faced mathematically equivalent decisions framed as either an opportunity to keep (gain frame) or lose (loss frame) part of an initial endowment. Periodically, participants were provided with positive (e.g., "Nice!") or negative (e.g., "Lame!") feedback about their choices. Such feedback was provided by either a confederate (Experiment 1) or a gender-matched close friend (Experiment 2). As expected, the framing effect was observed in both experiments. Critically, an individual's susceptibility to the framing effect was modulated by the valence of the SFB, but only when the feedback provider was a close friend. This effect was reflected in the activation patterns of ventromedial prefrontal cortex and posterior cingulate cortex, regions involved in complex decision-making. Taken together, these results highlight social closeness as an important factor in understanding the impact of SFB on neural mechanisms of decision-making.

Negative transcriptional control of ERBB2 gene by MBP-1 and HDAC1: diagnostic implications in breast cancer

International Nuclear Information System (INIS)

Contino, Flavia; Mazzarella, Claudia; Ferro, Arianna; Lo Presti, Mariavera; Roz, Elena; Lupo, Carmelo; Perconti, Giovanni; Giallongo, Agata; Feo, Salvatore

2013-01-01

The human ERBB2 gene is frequently amplified in breast tumors, and its high expression is associated with poor prognosis. We previously reported a significant inverse correlation between Myc promoter-binding protein-1 (MBP-1) and ERBB2 expression in primary breast invasive ductal carcinoma (IDC). MBP-1 is a transcriptional repressor of the c-MYC gene that acts by binding to the P2 promoter; only one other direct target of MBP-1, the COX2 gene, has been identified so far. To gain new insights into the functional relationship linking MBP-1 and ERBB2 in breast cancer, we have investigated the effects of MBP-1 expression on endogenous ERBB2 transcript and protein levels, as well as on transcription promoter activity, by transient-transfection of SKBr3 cells. Reporter gene and chromatin immunoprecipitation assays were used to dissect the ERBB2 promoter and identify functional MBP-1 target sequences. We also investigated the relative expression of MBP-1 and HDAC1 in IDC and normal breast tissues by immunoblot analysis and immunohistochemistry. Transfection experiments and chromatin immunoprecipitation assays in SKBr3 cells indicated that MBP-1 negatively regulates the ERBB2 gene by binding to a genomic region between nucleotide −514 and −262 of the proximal promoter; consistent with this, a concomitant recruitment of HDAC1 and loss of acetylated histone H4 was observed. In addition, we found high expression of MBP-1 and HDAC1 in normal tissues and a statistically significant inverse correlation with ErbB2 expression in the paired tumor samples. Altogether, our in vitro and in vivo data indicate that the ERBB2 gene is a novel MBP-1 target, and immunohistochemistry analysis of primary tumors suggests that the concomitant high expression of MBP-1 and HDAC1 may be considered a diagnostic marker of cancer progression for breast IDC

Cardiac and electro-cortical concomitants of social feedback processing in women

Science.gov (United States)

van der Molen, Melle J. W.; Gunther Moor, Bregtje; van der Veen, Frederik M.; van der Molen, Maurits W.

2015-01-01

This study provides a joint analysis of the cardiac and electro-cortical—early and late P3 and feedback-related negativity (FRN)—responses to social acceptance and rejection feedback. Twenty-five female participants performed on a social- and age-judgment control task, in which they received feedback with respect to their liking and age judgments, respectively. Consistent with previous reports, results revealed transient cardiac slowing to be selectively prolonged to unexpected social rejection feedback. Late P3 amplitude was more pronounced to unexpected relative to expected feedback. Both early and late P3 amplitudes were shown to be context dependent, in that they were more pronounced to social as compared with non-social feedback. FRN amplitudes were more pronounced to unexpected relative to expected feedback, irrespective of context and feedback valence. This pattern of findings indicates that social acceptance and rejection feedback have widespread effects on bodily state and brain function, which are modulated by prior expectancies. PMID:25870439

Nonlatching positive feedback enables robust bimodality by decoupling expression noise from the mean

Energy Technology Data Exchange (ETDEWEB)

Razooky, Brandon S. [Rockefeller Univ., New York, NY (United States). Lab. of Virology and Infectious Disease; Gladstone Institutes (Virology and Immunology), San Francisco, CA (United States); Univ. of California, San Francisco, CA (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Nanophase Materials Science (CNMS); Univ. of Tennessee, Knoxville, TN (United States). Bredesen Center for Interdisciplinary; Cao, Youfang [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hansen, Maike M. K. [Gladstone Institutes (Virology and Immunology), San Francisco, CA (United States); Perelson, Alan S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Simpson, Michael L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Nanophase Materials Science (CNMS); Univ. of Tennessee, Knoxville, TN (United States). Bredesen Center for Interdisciplinary; Weinberger, Leor S. [Gladstone Institutes (Virology and Immunology), San Francisco, CA (United States); Univ. of California, San Francisco, CA (United States). Dept. of Biochemistry and Biophysics; Univ. of California, San Francisco, CA (United States). QB3: California Inst. of Quantitative Biosciences; Univ. of California, San Francisco, CA (United States). Dept. of Pharmaceutical Chemistry

2017-10-18

Fundamental to biological decision-making is the ability to generate bimodal expression patterns where two alternate expression states simultaneously exist. Here in this study, we use a combination of single-cell analysis and mathematical modeling to examine the sources of bimodality in the transcriptional program controlling HIV’s fate decision between active replication and viral latency. We find that the HIV Tat protein manipulates the intrinsic toggling of HIV’s promoter, the LTR, to generate bimodal ON-OFF expression, and that transcriptional positive feedback from Tat shifts and expands the regime of LTR bimodality. This result holds for both minimal synthetic viral circuits and full-length virus. Strikingly, computational analysis indicates that the Tat circuit’s non-cooperative ‘non-latching’ feedback architecture is optimized to slow the promoter’s toggling and generate bimodality by stochastic extinction of Tat. In contrast to the standard Poisson model, theory and experiment show that non-latching positive feedback substantially dampens the inverse noise-mean relationship to maintain stochastic bimodality despite increasing mean-expression levels. Given the rapid evolution of HIV, the presence of a circuit optimized to robustly generate bimodal expression appears consistent with the hypothesis that HIV’s decision between active replication and latency provides a viral fitness advantage. More broadly, the results suggest that positive-feedback circuits may have evolved not only for signal amplification but also for robustly generating bimodality by decoupling expression fluctuations (noise) from mean expression levels.

The Wheat Mediator Subunit TaMED25 Interacts with the Transcription Factor TaEIL1 to Negatively Regulate Disease Resistance against Powdery Mildew.

Science.gov (United States)

Liu, Jie; Zhang, Tianren; Jia, Jizeng; Sun, Jiaqiang

2016-03-01

Powdery mildew, caused by the biotrophic fungal pathogen Blumeria graminis f. sp. tritici, is a major limitation for the production of bread wheat (Triticum aestivum). However, to date, the transcriptional regulation of bread wheat defense against powdery mildew remains largely unknown. Here, we report the function and molecular mechanism of the bread wheat Mediator subunit 25 (TaMED25) in regulating the bread wheat immune response signaling pathway. Three homoalleles of TaMED25 from bread wheat were identified and mapped to chromosomes 5A, 5B, and 5D, respectively. We show that knockdown of TaMED25 by barley stripe mosaic virus-induced gene silencing reduced bread wheat susceptibility to the powdery mildew fungus during the compatible plant-pathogen interaction. Moreover, our results indicate that MED25 may play a conserved role in regulating bread wheat and barley (Hordeum vulgare) susceptibility to powdery mildew. Similarly, bread wheat ETHYLENE INSENSITIVE3-LIKE1 (TaEIL1), an ortholog of Arabidopsis (Arabidopsis thaliana) ETHYLENE INSENSITIVE3, negatively regulates bread wheat resistance against powdery mildew. Using various approaches, we demonstrate that the conserved activator-interacting domain of TaMED25 interacts physically with the separate amino- and carboxyl-terminal regions of TaEIL1, contributing to the transcriptional activation activity of TaEIL1. Furthermore, we show that TaMED25 and TaEIL1 synergistically activate ETHYLENE RESPONSE FACTOR1 (TaERF1) transcription to modulate bread wheat basal disease resistance to B. graminis f. sp. tritici by repressing the expression of pathogenesis-related genes and deterring the accumulation of reactive oxygen species. Collectively, we identify the TaMED25-TaEIL1-TaERF1 signaling module as a negative regulator of bread wheat resistance to powdery mildew. © 2016 American Society of Plant Biologists. All Rights Reserved.

CGILS: Results from the First Phase of an International Project to Understand the Physical Mechanisms of Low Cloud Feedbacks in Single Column Models

Science.gov (United States)

Zhang, Minghua; Bretherton, Christopher S.; Blossey, Peter N.; Austin, Phillip H.; Bacmeister, Julio T.; Bony, Sandrine; Brient, Florent; Cheedela, Suvarchal K.; Cheng, Anning; DelGenio, Anthony;

Transient feedback from fuel motion in metal IFR [Integral Fast Reactor] fuel

International Nuclear Information System (INIS)

Rhodes, E.A.; Stanford, G.S.; Regis, J.P.; Bauer, T.H.; Dickerman, C.E.

1990-01-01

Results from hodoscope data analyses are presented for TREAT transient-overpower tests M5 through M7 with emphasis on transient feedback mechanisms, including prefailure expansion at the tops of the fuel pins, subsequent dispersive axial fuel motion, and losses in relative worth of the fuel pins during the tests. Tests M5 and M6 were the first TOP tests of margin to cladding branch and prefailure elongation of D9-clad ternary (U-Pu-Zr) IFR-type fuel. Test M7 extended these results to high-burnup fuel and also initiated transient testing of HT9-clad binary (U-Zr) FFTF-driver fuel. Results show significant prefailure negative reactivity feedback and strongly negative feedback from fuel driven to failure. 4 refs., 6 figs

The PRR11-SKA2 Bidirectional Transcription Unit Is Negatively Regulated by p53 through NF-Y in Lung Cancer Cells

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Yitao Wang

2017-03-01

Full Text Available We previously identified proline-rich protein 11 (PRR11 as a novel cancer-related gene that is implicated in the regulation of cell cycle and tumorigenesis. Our recent study demonstrated that PRR11 and its adjacent gene, kinetochore associated 2 (SKA2, constitute a classic head-to-head gene pair that is coordinately regulated by nuclear factor Y (NF-Y. In the present study, we further show that the PRR11-SKA2 bidirectional transcription unit is an indirect target of the tumor suppressor p53. A luciferase reporter assay revealed that overexpression of wild type p53, but not mutant p53, significantly represses the basal activity and NF-Y mediated transactivation of the PRR11-SKA2 bidirectional promoter. Deletion and mutation analysis of the PRR11-SKA2 promoter revealed that p53-mediated PRR11-SKA2 repression is dependent on the presence of functional NF-Y binding sites. Furthermore, a co-immunoprecipitation assay revealed that p53 associates with NF-Y in lung cancer cells, and a chromatin immunoprecipitation assay showed that p53 represses PRR11-SKA2 transcription by reducing the binding amount of NF-Y in the PRR11-SKA2 promoter region. Consistently, the ability of p53 to downregulate PRR11-SKA2 transcription was significantly attenuated upon siRNA-mediated depletion of nuclear factor Y subunit beta (NF-YB. Notably, lung cancer patients with lower expression of either PRR11 or SKA2 along with wild type p53 exhibited the best overall survival compared with others with p53 mutation and/or higher expression of either PRR11 or SKA2. Taken together, our results demonstrate that p53 negatively regulates the expression of the PRR11-SKA2 bidirectional transcription unit through NF-Y, suggesting that the inability to repress the PRR11-SKA2 bidirectional transcription unit after loss of p53 might contribute to tumorigenesis.

Estimation of power feedback parameters of the IBR-2M reactor by square wave reactivity

International Nuclear Information System (INIS)

Pepelyshev, Yu.N.; Popov, A.K.; Sumkhuu, D.

2016-01-01

Parameters of the IBR-2M reactor power feedback (PFB) are estimated based on the analysis of power transients caused by deliberate square wave reactivity when the pulsed reactor operates in the self-regulation mode. The PFB of the IBR-2M is described by three linear first-order differential equations. Two components of the PFB are responsible for the negative feedback and one, for the positive. The overall feedback is negative, i.e., it has a stabilizing effect for the operation of the reactor. The slowest negative component of the PFB is probably caused by heating of the fuel. Periodically repeated in the process of exploitation, estimation of the PFB parameters is one of the methods to ensure safety operation of the reactor. [ru

Feedback regulation of bile acid synthesis in human liver: Importance of HNF-4α for regulation of CYP7A1

International Nuclear Information System (INIS)

Abrahamsson, Anna; Gustafsson, Ulf; Ellis, Ewa; Nilsson, Lisa-Mari; Sahlin, Staffan; Bjoerkhem, Ingemar; Einarsson, Curt

2005-01-01

A great number of nuclear factors are involved in the negative feedback mechanism regulating bile acid synthesis. There are two major ways for the negative feedback to effect the synthesis; the SHP-dependent, involving FXR, and the SHP-independent way, affecting HNF-4α. We studied 23 patients with gallstone disease. Eight patients were treated with chenodeoxycholic acid, 7 with cholestyramine prior to operation, and 8 served as controls. Liver biopsies were analyzed with Real-time-PCR. In the cholestyramine-treated group mRNA levels of CYP7A1 were increased about 10-fold. Treatment with CDCA decreased the mRNA levels of CYP7A1 by about 70%. The mRNA levels of CYP8B1, CYP27A1, and CYP7B1 were not significantly altered in the treated groups. The analysis of mRNA levels for HNF-4α showed 64% higher levels in the cholestyramine-treated group compared to the controls. These levels showed positive and highly significant correlation to the levels of mRNA of CYP7A1 when studied in all three groups together. FXR, SHP, and LRH-1/FTF were not significantly affected by the different treatments. Our results indicate that when bile acid synthesis is upregulated by cholestyramine treatment the SHP-independent pathway for controlling CYP7A1 transcription dominates over the SHP-dependent pathway

HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans.

Directory of Open Access Journals (Sweden)

Won Hee Jung

2010-11-01

Full Text Available The fungal pathogen Cryptococcus neoformans is a major cause of illness in immunocompromised individuals such as AIDS patients. The ability of the fungus to acquire nutrients during proliferation in host tissue and the ability to elaborate a polysaccharide capsule are critical determinants of disease outcome. We previously showed that the GATA factor, Cir1, is a major regulator both of the iron uptake functions needed for growth in host tissue and the key virulence factors such as capsule, melanin and growth at 37°C. We are interested in further defining the mechanisms of iron acquisition from inorganic and host-derived iron sources with the goal of understanding the nutritional adaptation of C. neoformans to the host environment. In this study, we investigated the roles of the HAP3 and HAPX genes in iron utilization and virulence. As in other fungi, the C. neoformans Hap proteins negatively influence the expression of genes encoding respiratory and TCA cycle functions under low-iron conditions. However, we also found that HapX plays both positive and negative roles in the regulation of gene expression, including a positive regulatory role in siderophore transporter expression. In addition, HapX also positively regulated the expression of the CIR1 transcript. This situation is in contrast to the negative regulation by HapX of genes encoding GATA iron regulatory factors in Aspergillus nidulans and Schizosaccharomyces pombe. Although both hapX and hap3 mutants were defective in heme utilization in culture, only HapX made a contribution to virulence, and loss of HapX in a strain lacking the high-affinity iron uptake system did not cause further attenuation of disease. Therefore, HapX appears to have a minimal role during infection of mammalian hosts and instead may be an important regulator of environmental iron uptake functions. Overall, these results indicated that C. neoformans employs multiple strategies for iron acquisition during infection.

Synergy of feedback mechanisms in gene regulation systems with promoter and repressor transcription factors

Czech Academy of Sciences Publication Activity Database

Šrobár, Fedor

2008-01-01

Roč. 6, č. 1 (2008), s. 38-44 ISSN 1895-1082 Institutional research plan: CEZ:AV0Z20670512 Keywords : biophysics * feedback * signal flow graphs Subject RIV: BO - Biophysics Impact factor: 0.448, year: 2008

Follower-Centered Perspective on Feedback: Effects of Feedback Seeking on Identification and Feedback Environment

OpenAIRE

Gong, Zhenxing; Li, Miaomiao; Qi, Yaoyuan; Zhang, Na

2017-01-01

In the formation mechanism of the feedback environment, the existing research pays attention to external feedback sources and regards individuals as objects passively accepting feedback. Thus, the external source fails to realize the individuals’ need for feedback, and the feedback environment cannot provide them with useful information, leading to a feedback vacuum. The aim of this study is to examine the effect of feedback-seeking by different strategies on the supervisor-feedback environme...

Sensitivity of reactivity feedback due to core bowing in a metallic-fueled core

International Nuclear Information System (INIS)

Nakagawa, Masatoshi; Kawashima, Masatoshi; Endo, Hiroshi; Nishimura, Tomohiro

1991-01-01

A sensitivity study has been carried out on negative reactivity feedback caused by core bowing to assess the potential effectiveness of FBR passive safety features in regard to withstanding an anticipated transient without scram (ATWS). In the present study, an analysis has been carried to obtain the best material and geometrical conditions concerning the core restraint system out for several power to flow rates (P/F), up to 2.0 for a 300 MWe metallic-fueled core. From this study, it was clarified that the pad stiffness at an above core loading pads (ACLP) needs to be large enough to ensure negative reactivity feedback against ATWS. It was also clarified that there is an upper limit for the clearances between ducts at ACLP. A new concept, in regard to increasing the absolute value for negative reactivity feedback due to core bowing at ATWS, is proposed and discussed. (author)

Bunch-motion feedback for B-factories

International Nuclear Information System (INIS)

Lambertson, G.R.

1992-09-01

The colliding electron and positron beams in a B-factory must have average current of one ampere or more to produce the required luminosity. The high current interacts with structures in the beam tube to drive strong coupled-bunch (c.b.) instabilities. To suppress these instabilities requires negative feedback of the bunch motions. Beam impedances arising from strong rf cavity modes should first be reduced to make the required feedback damping rate practical and the cost economical. In what follows, control of transverse motions will be discussed first, then longitudinal. We shall use the parameters of the 3.1 GeV ring of PEP-II to illustrate the general requirements

Large-scale transcriptome data reveals transcriptional activity of fission yeast LTR retrotransposons

DEFF Research Database (Denmark)

Mourier, Tobias; Willerslev, Eske

2010-01-01

of transcriptional activity are observed from both strands of solitary LTR sequences. Transcriptome data collected during meiosis suggests that transcription of solitary LTRs is correlated with the transcription of nearby protein-coding genes. CONCLUSIONS: Presumably, the host organism negatively regulates...

Feedback, Lineages and Self-Organizing Morphogenesis.

Directory of Open Access Journals (Sweden)

Sameeran Kunche

2016-03-01

Full Text Available Feedback regulation of cell lineage progression plays an important role in tissue size homeostasis, but whether such feedback also plays an important role in tissue morphogenesis has yet to be explored. Here we use mathematical modeling to show that a particular feedback architecture in which both positive and negative diffusible signals act on stem and/or progenitor cells leads to the appearance of bistable or bi-modal growth behaviors, ultrasensitivity to external growth cues, local growth-driven budding, self-sustaining elongation, and the triggering of self-organization in the form of lamellar fingers. Such behaviors arise not through regulation of cell cycle speeds, but through the control of stem or progenitor self-renewal. Even though the spatial patterns that arise in this setting are the result of interactions between diffusible factors with antagonistic effects, morphogenesis is not the consequence of Turing-type instabilities.

Feedback, Lineages and Self-Organizing Morphogenesis

Science.gov (United States)

Calof, Anne L.; Lowengrub, John S.; Lander, Arthur D.

2016-01-01

Feedback regulation of cell lineage progression plays an important role in tissue size homeostasis, but whether such feedback also plays an important role in tissue morphogenesis has yet to be explored. Here we use mathematical modeling to show that a particular feedback architecture in which both positive and negative diffusible signals act on stem and/or progenitor cells leads to the appearance of bistable or bi-modal growth behaviors, ultrasensitivity to external growth cues, local growth-driven budding, self-sustaining elongation, and the triggering of self-organization in the form of lamellar fingers. Such behaviors arise not through regulation of cell cycle speeds, but through the control of stem or progenitor self-renewal. Even though the spatial patterns that arise in this setting are the result of interactions between diffusible factors with antagonistic effects, morphogenesis is not the consequence of Turing-type instabilities. PMID:26989903

From feedback- to response-based performance monitoring in active and observational learning.

Science.gov (United States)

Bellebaum, Christian; Colosio, Marco

2014-09-01

Humans can adapt their behavior by learning from the consequences of their own actions or by observing others. Gradual active learning of action-outcome contingencies is accompanied by a shift from feedback- to response-based performance monitoring. This shift is reflected by complementary learning-related changes of two ACC-driven ERP components, the feedback-related negativity (FRN) and the error-related negativity (ERN), which have both been suggested to signal events "worse than expected," that is, a negative prediction error. Although recent research has identified comparable components for observed behavior and outcomes (observational ERN and FRN), it is as yet unknown, whether these components are similarly modulated by prediction errors and thus also reflect behavioral adaptation. In this study, two groups of 15 participants learned action-outcome contingencies either actively or by observation. In active learners, FRN amplitude for negative feedback decreased and ERN amplitude in response to erroneous actions increased with learning, whereas observational ERN and FRN in observational learners did not exhibit learning-related changes. Learning performance, assessed in test trials without feedback, was comparable between groups, as was the ERN following actively performed errors during test trials. In summary, the results show that action-outcome associations can be learned similarly well actively and by observation. The mechanisms involved appear to differ, with the FRN in active learning reflecting the integration of information about own actions and the accompanying outcomes.

Using negative and positive social feedback from a robotic agent to save energy

NARCIS (Netherlands)

Midden, C.J.H.; Ham, J.R.C.; Chatterjee, S.; Dev, P.

2009-01-01

In this paper we explore the persuasive effects of social feedback, as provided by an embodied agent, on behavioral change. In a lab setting, two experiments were conducted in which participants had the opportunity to conserve energy while carrying out washing tasks with a simulated washing machine.

Bullying and negative appearance feedback among adolescents: Is it objective or misperceived weight that matters?

Science.gov (United States)

Lee, Kirsty; Dale, Jeremy; Guy, Alexa; Wolke, Dieter

2018-02-01

This study investigated (1) whether involvement in bullying as a bully, victim or bully-victim was associated with objectively measured overweight or underweight, or whether it was related to weight misperception (i.e., inaccurate perceptions), and (2) whether appearance-specific feedback mediated the relationship between bullying and weight misperception. In Stage 1, 2782 adolescents aged 11-16 years from British secondary schools were screened for peer bullying and victimisation. In Stage 2, 411 adolescents with weight and height data (objective n = 319, self-report n = 92) also self-reported on their weight perception and appearance-specific feedback. Neither bullying nor victimisation were related to objective underweight or overweight. Victims were at increased odds of overweight misperception, while bully-victims were at increased odds of underweight misperception. Additionally, there was an indirect effect of appearance feedback on overweight misperception in bully-victims. Both victims and bully-victims are at increased risk of weight misperception, posing further detrimental effects to their health and wellbeing. Copyright © 2017. Published by Elsevier Ltd.

A positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells

Energy Technology Data Exchange (ETDEWEB)

Zhang, Qiao, E-mail: zhangqiao200824@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Yang, Zhe, E-mail: zheyang@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Wang, Weiping, E-mail: wwp@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Guo, Ting, E-mail: luckyguoting@bjmu.edu.cn [Department of Gastrointestinal Translation Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital, 52 Fucheng Road, 100142 Beijing (China); Jia, Zhuqing, E-mail: zhuqingjia@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Ma, Kangtao, E-mail: makangtao11@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Zhou, Chunyan, E-mail: chunyanzhou@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China)

2014-07-04

Highlights: • ISL-1 is highly expressed in human pancreatic β-cells and DLBCL. • ISL-1 accelerates the tumorigenesis of DLBCL in vivo. • c-Myc positively regulates ISL-1 expression in DLBCL but not in pancreatic β-cells. • ISL-1 and c-Myc forms an ISL-1/c-Myc transcriptional complex only in DLBCL. • Positive feedback regulation of ISL-1 does not exist in normal pancreatic β-cell. - Abstract: Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, has been reported to play essential roles in promoting adult pancreatic β-cells proliferation. Recent studies indicate that ISL-1 may also involve in the occurrence of a variety of tumors. However, whether ISL-1 has any functional effect on tumorigenesis, and what are the differences on ISL-1 function in distinct conditions, are completely unknown. In this study, we found that ISL-1 was highly expressed in human pancreatic β-cells, as well as in diffuse large B cell lymphoma (DLBCL), but to a much less extent in other normal tissues or tumor specimens. Further study revealed that ISL-1 promoted the proliferation of pancreatic β-cells and DLBCL cells, and also accelerated the tumorigenesis of DLBCL in vivo. We also found that ISL-1 could activate c-Myc transcription not only in pancreatic β-cells but also in DLBCL cells. However, a cell-specific feedback regulation was detectable only in DLBCL cells. This auto-regulatory loop was established by the interaction of ISL-1 and c-Myc to form an ISL-1/c-Myc transcriptional complex, and synergistically to promote ISL-1 transcription through binding on the ISL-1 promoter. Taken together, our results demonstrate a positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells, which might result in the functional diversities of ISL-1 in different physiological and pathological processes.

A positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells

International Nuclear Information System (INIS)

Zhang, Qiao; Yang, Zhe; Wang, Weiping; Guo, Ting; Jia, Zhuqing; Ma, Kangtao; Zhou, Chunyan

2014-01-01

Highlights: • ISL-1 is highly expressed in human pancreatic β-cells and DLBCL. • ISL-1 accelerates the tumorigenesis of DLBCL in vivo. • c-Myc positively regulates ISL-1 expression in DLBCL but not in pancreatic β-cells. • ISL-1 and c-Myc forms an ISL-1/c-Myc transcriptional complex only in DLBCL. • Positive feedback regulation of ISL-1 does not exist in normal pancreatic β-cell. - Abstract: Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, has been reported to play essential roles in promoting adult pancreatic β-cells proliferation. Recent studies indicate that ISL-1 may also involve in the occurrence of a variety of tumors. However, whether ISL-1 has any functional effect on tumorigenesis, and what are the differences on ISL-1 function in distinct conditions, are completely unknown. In this study, we found that ISL-1 was highly expressed in human pancreatic β-cells, as well as in diffuse large B cell lymphoma (DLBCL), but to a much less extent in other normal tissues or tumor specimens. Further study revealed that ISL-1 promoted the proliferation of pancreatic β-cells and DLBCL cells, and also accelerated the tumorigenesis of DLBCL in vivo. We also found that ISL-1 could activate c-Myc transcription not only in pancreatic β-cells but also in DLBCL cells. However, a cell-specific feedback regulation was detectable only in DLBCL cells. This auto-regulatory loop was established by the interaction of ISL-1 and c-Myc to form an ISL-1/c-Myc transcriptional complex, and synergistically to promote ISL-1 transcription through binding on the ISL-1 promoter. Taken together, our results demonstrate a positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells, which might result in the functional diversities of ISL-1 in different physiological and pathological processes

How Residents Learn From Patient Feedback: A Multi-Institutional Qualitative Study of Pediatrics Residents' Perspectives.

Science.gov (United States)

Bogetz, Alyssa L; Orlov, Nicola; Blankenburg, Rebecca; Bhavaraju, Vasudha; McQueen, Alisa; Rassbach, Caroline

2018-04-01

Residents may view feedback from patients and their families with greater skepticism than feedback from supervisors and peers. While discussing patient and family feedback with faculty may improve residents' acceptance of feedback and learning, specific strategies have not been identified. We explored pediatrics residents' perspectives of patient feedback and identified strategies that promote residents' reflection on and learning from feedback. In this multi-institutional, qualitative study conducted in June and July 2016, we conducted focus groups with a purposive sample of pediatrics residents after their participation in a randomized controlled trial in which they received written patient feedback and either discussed it with faculty or reviewed it independently. Focus group transcripts were audiorecorded, transcribed, and analyzed for themes using the constant comparative approach associated with grounded theory. Thirty-six of 92 (39%) residents participated in 7 focus groups. Four themes emerged: (1) residents valued patient feedback but felt it may lack the specificity they desire; (2) discussing feedback with a trusted faculty member was helpful for self-reflection; (3) residents identified 5 strategies faculty used to facilitate their openness to and acceptance of patient feedback (eg, help resident overcome emotional responses to feedback and situate feedback in the context of lifelong learning); and (4) residents' perceptions of feedback credibility improved when faculty observed patient encounters and solicited feedback on the resident's behalf prior to discussions. Discussing patient feedback with faculty provided important scaffolding to enhance residents' openness to and reflection on patient feedback.

Eukaryotic transcription factors

DEFF Research Database (Denmark)

Staby, Lasse; O'Shea, Charlotte; Willemoës, Martin

2017-01-01

Gene-specific transcription factors (TFs) are key regulatory components of signaling pathways, controlling, for example, cell growth, development, and stress responses. Their biological functions are determined by their molecular structures, as exemplified by their structured DNA-binding domains...... regions with function-related, short sequence motifs and molecular recognition features with structural propensities. This review focuses on molecular aspects of TFs, which represent paradigms of ID-related features. Through specific examples, we review how the ID-associated flexibility of TFs enables....... It is furthermore emphasized how classic biochemical concepts like allostery, conformational selection, induced fit, and feedback regulation are undergoing a revival with the appreciation of ID. The review also describes the most recent advances based on computational simulations of ID-based interaction mechanisms...

Acute Stress Modulates Feedback Processing in Men and Women : Differential Effects on the Feedback-Related Negativity and Theta and Beta Power

NARCIS (Netherlands)

Banis, Stella; Geerligs, Linda; Lorist, Monicque M.; Banis, Hendrika

2014-01-01

Sex-specific prevalence rates in mental and physical disorders may be partly explained by sex differences in physiological stress responses. Neural networks that might be involved are those underlying feedback processing. Aim of the present EEG study was to investigate whether acute stress alters

Electrocortical reactivity to social feedback in youth: A pilot study of the Island Getaway task

Directory of Open Access Journals (Sweden)

Autumn Kujawa

2014-10-01

Full Text Available Peer relationships become a major concern in adolescence, yet event-related potential (ERP measures of reactivity to social feedback in adolescence are limited. In this pilot study, we tested a novel task to elicit reactivity to social feedback in youth. Participants (10–15 years old; 57.9% male; N = 19 played a game that involved exchanging personal information with peers, voting to remove players from the game, and receiving rejection and acceptance feedback from peers. Results indicated that participants modified their voting behavior in response to peer feedback, and rejection feedback was associated with a negativity in the ERP wave compared to acceptance (i.e., the feedback negativity, FN. The FN predicted behavioral patterns, such that participants who showed greater neural reactivity to social feedback were less likely to reject co-players. Preliminary analyses suggest that the task may be a useful measure of individual differences: adolescents higher in social anxiety symptoms were less likely to reject peers and showed an enhanced FN to rejection vs. acceptance feedback, and higher depressive symptoms predicted an increased FN to rejection specifically. Results suggest that the FN elicited by social feedback may be a useful, economical neural measure of social processing across development and in clinical research.

Self-evaluation and peer-feedback of medical students' communication skills using a web-based video annotation system. Exploring content and specificity.

Science.gov (United States)

Hulsman, Robert L; van der Vloodt, Jane

2015-03-01

Self-evaluation and peer-feedback are important strategies within the reflective practice paradigm for the development and maintenance of professional competencies like medical communication. Characteristics of the self-evaluation and peer-feedback annotations of medical students' video recorded communication skills were analyzed. Twenty-five year 4 medical students recorded history-taking consultations with a simulated patient, uploaded the video to a web-based platform, marked and annotated positive and negative events. Peers reviewed the video and self-evaluations and provided feedback. Analyzed were the number of marked positive and negative annotations and the amount of text entered. Topics and specificity of the annotations were coded and analyzed qualitatively. Students annotated on average more negative than positive events. Additional peer-feedback was more often positive. Topics most often related to structuring the consultation. Students were most critical about their biomedical topics. Negative annotations were more specific than positive annotations. Self-evaluations were more specific than peer-feedback and both show a significant correlation. Four response patterns were detected that negatively bias specificity assessment ratings. Teaching students to be more specific in their self-evaluations may be effective for receiving more specific peer-feedback. Videofragmentrating is a convenient tool to implement reflective practice activities like self-evaluation and peer-feedback to the classroom in the teaching of clinical skills. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

An Industrial Model Based Disturbance Feedback Control Scheme

DEFF Research Database (Denmark)

Kawai, Fukiko; Nakazawa, Chikashi; Vinther, Kasper

2014-01-01

This paper presents a model based disturbance feedback control scheme. Industrial process systems have been traditionally controlled by using relay and PID controller. However these controllers are affected by disturbances and model errors and these effects degrade control performance. The authors...... propose a new control method that can decrease the negative impact of disturbance and model errors. The control method is motivated by industrial practice by Fuji Electric. Simulation tests are examined with a conventional PID controller and the disturbance feedback control. The simulation results...

Effects of intrinsic motivation on feedback processing during learning.

Science.gov (United States)

DePasque, Samantha; Tricomi, Elizabeth

2015-10-01

Learning commonly requires feedback about the consequences of one's actions, which can drive learners to modify their behavior. Motivation may determine how sensitive an individual might be to such feedback, particularly in educational contexts where some students value academic achievement more than others. Thus, motivation for a task might influence the value placed on performance feedback and how effectively it is used to improve learning. To investigate the interplay between intrinsic motivation and feedback processing, we used functional magnetic resonance imaging (fMRI) during feedback-based learning before and after a novel manipulation based on motivational interviewing, a technique for enhancing treatment motivation in mental health settings. Because of its role in the reinforcement learning system, the striatum is situated to play a significant role in the modulation of learning based on motivation. Consistent with this idea, motivation levels during the task were associated with sensitivity to positive versus negative feedback in the striatum. Additionally, heightened motivation following a brief motivational interview was associated with increases in feedback sensitivity in the left medial temporal lobe. Our results suggest that motivation modulates neural responses to performance-related feedback, and furthermore that changes in motivation facilitate processing in areas that support learning and memory. Copyright © 2015. Published by Elsevier Inc.

Effects of Intrinsic Motivation on Feedback Processing During Learning

Science.gov (United States)

DePasque, Samantha; Tricomi, Elizabeth

2015-01-01

Learning commonly requires feedback about the consequences of one’s actions, which can drive learners to modify their behavior. Motivation may determine how sensitive an individual might be to such feedback, particularly in educational contexts where some students value academic achievement more than others. Thus, motivation for a task might influence the value placed on performance feedback and how effectively it is used to improve learning. To investigate the interplay between intrinsic motivation and feedback processing, we used functional magnetic resonance imaging (fMRI) during feedback-based learning before and after a novel manipulation based on motivational interviewing, a technique for enhancing treatment motivation in mental health settings. Because of its role in the reinforcement learning system, the striatum is situated to play a significant role in the modulation of learning based on motivation. Consistent with this idea, motivation levels during the task were associated with sensitivity to positive versus negative feedback in the striatum. Additionally, heightened motivation following a brief motivational interview was associated with increases in feedback sensitivity in the left medial temporal lobe. Our results suggest that motivation modulates neural responses to performance-related feedback, and furthermore that changes in motivation facilitates processing in areas that support learning and memory. PMID:26112370

Self-verification in clinical depression: the desire for negative evaluation.

Science.gov (United States)

Giesler, R B; Josephs, R A; Swann, W B

1996-08-01

Do clinically depressed individuals seek favorable or unfavorable information about the self? Self-verification theory makes the counterintuitive prediction that depressed individuals solicit feedback that confirms their negative self-views. To test this prediction, participants were classified on the basis of a structured clinical interview and self-report measures into high-esteem, low self-esteem, and depressed groups. All participants were offered a choice between receiving favorable or unfavorable feedback; 82% of the depressed participants chose the unfavorable feedback, compared to 64% of the low self-esteem participants and 25% of the high self-esteem participants. Additional evidence indicated that depressed individuals also failed to exploit fully an opportunity to acquire favorable evaluations that were self-verifying. The authors discuss how seeking negative evaluations and failing to seek favorable evaluations may help maintain depression.

The Wheat Mediator Subunit TaMED25 Interacts with the Transcription Factor TaEIL1 to Negatively Regulate Disease Resistance against Powdery Mildew1

Science.gov (United States)

Zhang, Tianren; Jia, Jizeng; Sun, Jiaqiang

2016-01-01

Powdery mildew, caused by the biotrophic fungal pathogen Blumeria graminis f. sp. tritici, is a major limitation for the production of bread wheat (Triticum aestivum). However, to date, the transcriptional regulation of bread wheat defense against powdery mildew remains largely unknown. Here, we report the function and molecular mechanism of the bread wheat Mediator subunit 25 (TaMED25) in regulating the bread wheat immune response signaling pathway. Three homoalleles of TaMED25 from bread wheat were identified and mapped to chromosomes 5A, 5B, and 5D, respectively. We show that knockdown of TaMED25 by barley stripe mosaic virus-induced gene silencing reduced bread wheat susceptibility to the powdery mildew fungus during the compatible plant-pathogen interaction. Moreover, our results indicate that MED25 may play a conserved role in regulating bread wheat and barley (Hordeum vulgare) susceptibility to powdery mildew. Similarly, bread wheat ETHYLENE INSENSITIVE3-LIKE1 (TaEIL1), an ortholog of Arabidopsis (Arabidopsis thaliana) ETHYLENE INSENSITIVE3, negatively regulates bread wheat resistance against powdery mildew. Using various approaches, we demonstrate that the conserved activator-interacting domain of TaMED25 interacts physically with the separate amino- and carboxyl-terminal regions of TaEIL1, contributing to the transcriptional activation activity of TaEIL1. Furthermore, we show that TaMED25 and TaEIL1 synergistically activate ETHYLENE RESPONSE FACTOR1 (TaERF1) transcription to modulate bread wheat basal disease resistance to B. graminis f. sp. tritici by repressing the expression of pathogenesis-related genes and deterring the accumulation of reactive oxygen species. Collectively, we identify the TaMED25-TaEIL1-TaERF1 signaling module as a negative regulator of bread wheat resistance to powdery mildew. PMID:26813794

Reduced risk avoidance and altered neural correlates of feedback processing in patients with borderline personality disorder.

Science.gov (United States)

Endrass, Tanja; Schuermann, Beate; Roepke, Stefan; Kessler-Scheil, Sonia; Kathmann, Norbert

2016-09-30

Patients with borderline personality disorder (BPD) show deficits in reward-guided decision making and learning. The present study examined risk-taking behavior in combination with feedback processing. Eighteen BPD patients and 18 healthy controls performed a probabilistic two-choice gambling task, while an electroencephalogram was recorded. Options differed in risk, but were identical in expected value and outcome probability. The feedback-related negativity (FRN) and the feedback-related P300 were analyzed. Healthy controls preferred low-risk over high-risk options, whereas BPD patients chose both option with equal probability. FRN amplitudes were reduced in BPD, but effects of feedback valence and risk did not differ between groups. This suggests attenuated outcome processing in the anterior cingulate cortex, but intact reward prediction error signaling. Furthermore, the modulation of the feedback-related P300 with feedback valence and risk was smaller in BPD patients, and decreased P300 amplitudes were associated with increased behavioral risk-taking behavior. These findings could relate to the reduced ability of BPD patients to learn and adequately adjust their behavior based on feedback information, possibly due to reduced significance of negative feedback. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

On the evocability of a positive oestrogen feedback action on LH secretion in transsexual men and women.

Science.gov (United States)

Dörner, G; Rohde, W; Seidel, K; Haas, W; Schott, G S

1976-03-01

In transsexual men with homosexual behaviour and intact testicular function, as well as in homosexual men with normal gender identity, following a negative oestrogen feedback effect a delayed positive oestrogen feedback action on LH secretion was evoked. By contrast, in transsexual men with hypo- or asexuality and intact testes or hypergonadotrophic hypo- or agonadism, as well as in heterosexual men with normal gender identity, a negative oestrogen feedback effect was not followed by a positive feedback action on LH release. In transsexual women with homosexual behaviour and oligo- and/or hypomenorrhoea, only a weak or at best moderate positive oestrogen feedback action on LH release was evocable, similarly as in castrated and oestrogen-primed heterosexual men. By contrast, in a transsexual woman with bisexual behaviour and eumenorrhoea, a strong positive oestrogen feedback action on LH secretion was evocable, as well as in heterosexual women with normal gender identity.

Evaluating plant-soil feedback together with competition in a serpentine grassland.

Science.gov (United States)

Casper, Brenda B; Castelli, Jeffrey P

2007-05-01

Plants can alter biotic and abiotic soil characteristics in ways that feedback to change the performance of that same plant species relative to co-occurring plants. Most evidence for this plant-soil feedback comes from greenhouse studies of potted plants, and consequently, little is known about the importance of feedback in relation to other biological processes known to structure plant communities, such as plant-plant competition. In a field experiment with three C4 grasses, negative feedback was expressed through reduced survival and shoot biomass when seedlings were planted within existing clumps of conspecifics compared with clumps of heterospecifics. However, the combined effects of feedback and competition were species-specific. Only Andropogon gerardii exhibited feedback when competition with the clumps was allowed. For Sorghastrum nutans, strong interspecific competition eliminated the feedback expressed in the absence of competition, and Schizachyrium scoparium showed no feedback at all. That arbuscular mycorrhizal (AM) fungi may play a role in the feedback was indicated by higher AM root colonization with conspecific plant neighbours. We suggest that feedback and competition should not be viewed as entirely separate processes and that their importance in structuring plant communities cannot be judged in isolation from each other.

What's the FOX Got to Do with the KITten? Regulating the Lineage-Specific Transcriptional Landscape in GIST.

Science.gov (United States)

Lee, Donna M; Duensing, Anette

2018-02-01

Transcriptional regulation of the KIT receptor tyrosine kinase, a master regulator in gastrointestinal stromal tumors (GIST) and their precursors, the interstitial cells of Cajal (ICC), is part of a positive feedback loop involving the transcription factor ETV1. A new study now shows that the forkhead box (FOX) family transcription factor FOXF1 not only is an upstream regulator of ETV1 and hence ICC/GIST lineage-specific gene transcription, but also functions as lineage-specific pioneer factor with an active role in chromatin rearrangement to facilitate ETV1 binding and transcriptional activity. Cancer Discov; 8(2); 146-9. ©2018 AACR See related article by Ran et al., p. 234 . ©2018 American Association for Cancer Research.

Differential feedback regulation of ethylene biosynthesis in pulp and peel tissues of banana fruit.

Science.gov (United States)

Inaba, Akitsugu; Liu, Xuejun; Yokotani, Naoki; Yamane, Miki; Lu, Wang-Jin; Nakano, Ryohei; Kubo, Yasutaka

2007-01-01

The feedback regulation of ethylene biosynthesis in banana [Musa sp. (AAA group, Cavendish subgroup) cv. Grand Nain] fruit was investigated in an attempt to clarify the opposite effect of 1-methylcyclopropene (1-MCP), an ethylene action inhibitor, before and after the onset of ripening. 1-MCP pre-treatment completely prevented the ripening-induced effect of propylene in pre-climacteric banana fruit, whereas treatment after the onset of ripening stimulated ethylene production. In pre-climacteric fruit, higher concentrations of propylene suppressed ethylene production more strongly, despite their earlier ethylene-inducing effect. Exposure of the fruit ripened by propylene to 1-MCP increased ethylene production concomitantly with an increase in 1-aminocyclopropane-1-carboxylate (ACC) synthase activity and ACC content, and prevented a transient decrease in MA-ACS1 transcripts in the pulp tissues. In contrast, in the peel of ripening fruit, 1-MCP prevented the increase in ethylene production and subsequently the ripening process by reduction of the increase in MA-ACS1 and MA-ACO1 transcripts and of ACC synthase and ACC oxidase activities. These results suggest that ethylene biosynthesis in ripening banana fruit may be controlled negatively in the pulp tissue and positively in the peel tissue. This differential regulation by ethylene in pulp and peel tissues was also observed for MA-PL, MA-Exp, and MA-MADS genes.

Cultural shaping of neural responses: Feedback-related potentials vary with self-construal and face priming.

Science.gov (United States)

Hitokoto, Hidefumi; Glazer, James; Kitayama, Shinobu

2016-01-01

Previous work shows that when an image of a face is presented immediately prior to each trial of a speeded cognitive task (face-priming), the error-related negativity (ERN) is upregulated for Asians, but it is downregulated for Caucasians. These findings are consistent with the hypothesis that images of "generalized other" vary cross-culturally such that they evoke anxiety for Asians, whereas they serve as safety cues for Caucasians. Here, we tested whether the cross-cultural variation in the face-priming effect would be observed in a gambling paradigm. Caucasian Americans, Asian Americans, and Asian sojourners were exposed to a brief flash of a schematic face during a gamble. For Asian Americans, face-priming resulted in significant increases of both negative-going deflection of ERP upon negative feedback (feedback-related negativity [FRN]) and positive-going deflection of ERP upon positive feedback (feedback-related positivity [FRP]). For Caucasian Americans, face-priming showed a significant reversal, decreasing both FRN and FRP. The cultural difference in the face-priming effect in FRN and FRP was partially mediated by interdependent self-construal. Curiously, Asian sojourners showed a pattern similar to the one for Caucasian Americans. Our findings suggest that culture shapes neural pathways in both systematic and highly dynamic fashion. © 2015 Society for Psychophysiological Research.

Praise in Public, Criticize in Private? An Assessment of Performance Feedback Transparency in a Classroom Setting

Science.gov (United States)

Seevers, Matthew T.; Rowe, William J.; Skinner, Steven J.

2014-01-01

Conventional wisdom in sales management encourages public delivery of positive feedback, and private delivery of negative feedback. In stark contrast, U.S. educators typically provide all performance feedback in relative (if not strict) privacy to comply with the Family Educational Rights and Privacy Act (FERPA). To investigate this discrepancy,…

Construction and modelling of an inducible positive feedback loop stably integrated in a mammalian cell-line.

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Velia Siciliano

2011-06-01

Full Text Available Understanding the relationship between topology and dynamics of transcriptional regulatory networks in mammalian cells is essential to elucidate the biology of complex regulatory and signaling pathways. Here, we characterised, via a synthetic biology approach, a transcriptional positive feedback loop (PFL by generating a clonal population of mammalian cells (CHO carrying a stable integration of the construct. The PFL network consists of the Tetracycline-controlled transactivator (tTA, whose expression is regulated by a tTA responsive promoter (CMV-TET, thus giving rise to a positive feedback. The same CMV-TET promoter drives also the expression of a destabilised yellow fluorescent protein (d2EYFP, thus the dynamic behaviour can be followed by time-lapse microscopy. The PFL network was compared to an engineered version of the network lacking the positive feedback loop (NOPFL, by expressing the tTA mRNA from a constitutive promoter. Doxycycline was used to repress tTA activation (switch off, and the resulting changes in fluorescence intensity for both the PFL and NOPFL networks were followed for up to 43 h. We observed a striking difference in the dynamics of the PFL and NOPFL networks. Using non-linear dynamical models, able to recapitulate experimental observations, we demonstrated a link between network topology and network dynamics. Namely, transcriptional positive autoregulation can significantly slow down the "switch off" times, as compared to the non-autoregulated system. Doxycycline concentration can modulate the response times of the PFL, whereas the NOPFL always switches off with the same dynamics. Moreover, the PFL can exhibit bistability for a range of Doxycycline concentrations. Since the PFL motif is often found in naturally occurring transcriptional and signaling pathways, we believe our work can be instrumental to characterise their behaviour.

Construction and modelling of an inducible positive feedback loop stably integrated in a mammalian cell-line.

Science.gov (United States)

Siciliano, Velia; Menolascina, Filippo; Marucci, Lucia; Fracassi, Chiara; Garzilli, Immacolata; Moretti, Maria Nicoletta; di Bernardo, Diego

2011-06-01

Understanding the relationship between topology and dynamics of transcriptional regulatory networks in mammalian cells is essential to elucidate the biology of complex regulatory and signaling pathways. Here, we characterised, via a synthetic biology approach, a transcriptional positive feedback loop (PFL) by generating a clonal population of mammalian cells (CHO) carrying a stable integration of the construct. The PFL network consists of the Tetracycline-controlled transactivator (tTA), whose expression is regulated by a tTA responsive promoter (CMV-TET), thus giving rise to a positive feedback. The same CMV-TET promoter drives also the expression of a destabilised yellow fluorescent protein (d2EYFP), thus the dynamic behaviour can be followed by time-lapse microscopy. The PFL network was compared to an engineered version of the network lacking the positive feedback loop (NOPFL), by expressing the tTA mRNA from a constitutive promoter. Doxycycline was used to repress tTA activation (switch off), and the resulting changes in fluorescence intensity for both the PFL and NOPFL networks were followed for up to 43 h. We observed a striking difference in the dynamics of the PFL and NOPFL networks. Using non-linear dynamical models, able to recapitulate experimental observations, we demonstrated a link between network topology and network dynamics. Namely, transcriptional positive autoregulation can significantly slow down the "switch off" times, as compared to the non-autoregulated system. Doxycycline concentration can modulate the response times of the PFL, whereas the NOPFL always switches off with the same dynamics. Moreover, the PFL can exhibit bistability for a range of Doxycycline concentrations. Since the PFL motif is often found in naturally occurring transcriptional and signaling pathways, we believe our work can be instrumental to characterise their behaviour.

Acute effects of alcohol on feedback processing and outcome evaluation during risky decision-making: an ERP study.

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Euser, Anja S; van Meel, Catharina S; Snelleman, Michelle; Franken, Ingmar H A

2011-09-01

Although risky decision-making is one of the hallmarks of alcohol use disorders, relatively little is known about the acute psychopharmacological effects of alcohol on decision-making processes. The present study investigated the acute effects of alcohol on neural mechanisms underlying feedback processing and outcome evaluation during risky decision-making, using event-related brain potentials (ERPs). ERPs elicited by positive and negative feedback were recorded during performance of a modified version of the Balloon Analogue Risk Task in male participants receiving either a moderate dose of alcohol (0.65 g/kg alcohol; n = 32) or a non-alcoholic placebo beverage (n = 32). Overall, there was no significant difference in the mean number of pumps between the alcohol and the placebo condition. However, when analyzing over time, it was found that the alcohol group made more riskier choices at the beginning of the task than the placebo group. ERPs demonstrated that alcohol consumption did not affect early processing of negative feedback, indexed by the feedback-related negativity. By contrast, alcohol-intoxicated individuals showed significantly reduced P300 amplitudes in response to negative feedback as compared to sober controls, suggesting that more elaborate evaluation to losses was significantly diminished. These results suggest that alcohol consumption does not influence the ability to rapidly evaluate feedback valence, but rather the ability to assign sufficient attention to further process motivationally salient outcomes. Blunted P300 amplitudes may reflect poor integration of feedback across trials, particularly adverse ones. Consequently, alcohol may keep people from effectively predicting the probability of future gains and losses based on their reinforcement history.

Neurophysiological correlates of anhedonia in feedback processing

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Mies, Gabry W.; Van den Berg, Ivo; Franken, Ingmar H. A.; Smits, Marion; Van der Molen, Maurits W.; Van der Veen, Frederik M.

2013-01-01

Disturbances in feedback processing and a dysregulation of the neural circuit in which the cingulate cortex plays a key role have been frequently observed in depression. Since depression is a heterogeneous disease, instead of focusing on the depressive state in general, this study investigated the relations between the two core symptoms of depression, i.e., depressed mood and anhedonia, and the neural correlates of feedback processing using fMRI. The focus was on the different subdivisions of the anterior cingulate cortex (ACC). Undergraduates with varying levels of depressed mood and anhedonia performed a time-estimation task in which they received positive and negative feedback that was either valid or invalid (i.e., related vs. unrelated to actual performance). The rostral cingulate zone (RCZ), corresponding to the dorsal part of the ACC, was less active in response to feedback in more anhedonic individuals, after correcting for the influence of depressed mood, whereas the subgenual ACC was more active in these individuals. Task performance was not affected by anhedonia, however. No statistically significant effects were found for depressed mood above and beyond the effects of anhedonia. This study therefore implies that increasing levels of anhedonia involve changes in the neural circuitry underlying feedback processing. PMID:23532800

Ask and you shall receive: desire and receipt of feedback via Facebook predicts disordered eating concerns.

Science.gov (United States)

Hummel, Alexandra C; Smith, April R

2015-05-01

The current study examined whether certain types of Facebook content (i.e., status updates, comments) relate to eating concerns and attitudes. We examined the effects of seeking and receiving negative feedback via Facebook on disordered eating concerns in a sample of 185 undergraduate students followed for approximately 4 weeks. Results indicated that individuals with a negative feedback seeking style who received a high number of comments on Facebook were more likely to report disordered eating attitudes four weeks later. Additionally, individuals who received extremely negative comments in response to their personally revealing status updates were more likely to report disordered eating concerns four weeks later. Results of the current study provide preliminary evidence that seeking and receiving negative feedback via social networking sites can increase risk for disordered eating attitudes, and suggest that reducing maladaptive social networking usage may be an important target for prevention and intervention efforts aimed at reducing disordered eating attitudes. © 2014 Wiley Periodicals, Inc.

Targeting Prolyl Peptidases in Triple-Negative Breast Cancer

Science.gov (United States)

2017-02-01

ABSTRACT Triple negative breast cancer (TNBC) is an aggressive sub-type with limited treatment options and poor prognosis. The most life -threatening... negative feedback loops within the pathway limit their effectiveness . For example, AKT inhibitors cause increased expression of IGF1R/ErbB3 and, as a...AWARD NUMBER: W81XWH-16-1-0025 TITLE: Targeting Prolyl Peptidases in Triple- Negative Breast Cancer PRINCIPAL INVESTIGATOR: Carl G. Maki, PhD

Density-dependency and plant-soil feedback: former plant abundance influences competitive interactions between two grassland plant species through plant-soil feedbacks

NARCIS (Netherlands)

Xue, W.; Bezemer, T.M.; Berendse, Frank

2018-01-01

Backgrounds and aims Negative plant-soil feedbacks (PSFs) are thought to promote species coexistence, but most evidence is derived from theoretical models and data from plant monoculture experiments. Methods We grew Anthoxanthum odoratum and Centaurea jacea in field plots in monocultures and in

Does Constructive Performance Feedback Improve Citizenship Intentions and Job Satisfaction? The Roles of Perceived Opportunities for Advancement, Respect, and Mood

Science.gov (United States)

Sommer, Kristin L.; Kulkarni, Mukta

2012-01-01

Organizational experts have long touted the importance of delivering negative performance feedback in a manner that enhances employee receptivity to feedback, yet the broader impacts of constructive feedback have received relatively little attention. The present investigation explored the impact of constructive, critical feedback on organizational…

HER2 in Breast Cancer Stemness: A Negative Feedback Loop towards Trastuzumab Resistance

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Babak Nami

2017-04-01

Full Text Available HER2 receptor tyrosine kinase that is overexpressed in approximately 20% of all breast cancers (BCs is a poor prognosis factor and a precious target for BC therapy. Trastuzumab is approved by FDA to specifically target HER2 for treating HER2+ BC. However, about 60% of patients with HER2+ breast tumor develop de novo resistance to trastuzumab, partially due to the loss of expression of HER2 extracellular domain on their tumor cells. This is due to shedding/cleavage of HER2 by metalloproteinases (ADAMs and MMPs. HER2 shedding results in the accumulation of intracellular carboxyl-terminal HER2 (p95HER2, which is a common phenomenon in trastuzumab-resistant tumors and is suggested as a predictive marker for trastuzumab resistance. Up-regulation of the metalloproteinases is a poor prognosis factor and is commonly seen in mesenchymal-like cancer stem cells that are risen during epithelial to mesenchymal transition (EMT of tumor cells. HER2 cleavage during EMT can explain why secondary metastatic tumors with high percentage of mesenchymal-like cancer stem cells are mostly resistant to trastuzumab but still sensitive to lapatinib. Importantly, many studies report HER2 interaction with oncogenic/stemness signaling pathways including TGF-β/Smad, Wnt/β-catenin, Notch, JAK/STAT and Hedgehog. HER2 overexpression promotes EMT and the emergence of cancer stem cell properties in BC. Increased expression and activation of metalloproteinases during EMT leads to proteolytic cleavage and shedding of HER2 receptor, which downregulates HER2 extracellular domain and eventually increases trastuzumab resistance. Here, we review the hypothesis that a negative feedback loop between HER2 and stemness signaling drives resistance of BC to trastuzumab.

The stress-buffering effect of acute exercise: Evidence for HPA axis negative feedback.

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Zschucke, Elisabeth; Renneberg, Babette; Dimeo, Fernando; Wüstenberg, Torsten; Ströhle, Andreas

2015-01-01

According to the cross-stressor adaptation hypothesis, physically trained individuals show lower physiological and psychological responses to stressors other than exercise, e.g. psychosocial stress. Reduced stress reactivity may constitute a mechanism of action for the beneficial effects of exercise in maintaining mental health. With regard to neural and psychoneuroendocrine stress responses, the acute stress-buffering effects of exercise have not been investigated yet. A sample of highly trained (HT) and sedentary (SED) young men was randomized to either exercise on a treadmill at moderate intensity (60-70% VO2max; AER) for 30 min, or to perform 30 min of "placebo" exercise (PLAC). 90 min later, an fMRI experiment was conducted using an adapted version of the Montreal Imaging Stress Task (MIST). The subjective and psychoneuroendocrine (cortisol and α-amylase) changes induced by the exercise intervention and the MIST were assessed, as well as neural activations during the MIST. Finally, associations between the different stress responses were analysed. Participants of the AER group showed a significantly reduced cortisol response to the MIST, which was inversely related to the previous exercise-induced α-amylase and cortisol fluctuations. With regard to the sustained BOLD signal, we found higher bilateral hippocampus (Hipp) activity and lower prefrontal cortex (PFC) activity in the AER group. Participants with a higher aerobic fitness showed lower cortisol responses to the MIST. As the Hipp and PFC are brain structures prominently involved in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis, these findings indicate that the acute stress-buffering effect of exercise relies on negative feedback mechanisms. Positive affective changes after exercise appear as important moderators largely accounting for the effects related to physical fitness. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ultrafast Outflows: Galaxy-scale Active Galactic Nucleus Feedback

Science.gov (United States)

Wagner, A. Y.; Umemura, M.; Bicknell, G. V.

2013-01-01

We show, using global three-dimensional grid-based hydrodynamical simulations, that ultrafast outflows (UFOs) from active galactic nuclei (AGNs) result in considerable feedback of energy and momentum into the interstellar medium (ISM) of the host galaxy. The AGN wind interacts strongly with the inhomogeneous, two-phase ISM consisting of dense clouds embedded in a tenuous, hot, hydrostatic medium. The outflow floods through the intercloud channels, sweeps up the hot ISM, and ablates and disperses the dense clouds. The momentum of the UFO is primarily transferred to the dense clouds via the ram pressure in the channel flow, and the wind-blown bubble evolves in the energy-driven regime. Any dependence on UFO opening angle disappears after the first interaction with obstructing clouds. On kpc scales, therefore, feedback by UFOs operates similarly to feedback by relativistic AGN jets. Negative feedback is significantly stronger if clouds are distributed spherically rather than in a disk. In the latter case, the turbulent backflow of the wind drives mass inflow toward the central black hole. Considering the common occurrence of UFOs in AGNs, they are likely to be important in the cosmological feedback cycles of galaxy formation.

ULTRAFAST OUTFLOWS: GALAXY-SCALE ACTIVE GALACTIC NUCLEUS FEEDBACK

Energy Technology Data Exchange (ETDEWEB)

Wagner, A. Y.; Umemura, M. [Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577 (Japan); Bicknell, G. V., E-mail: ayw@ccs.tsukuba.ac.jp [Research School of Astronomy and Astrophysics, Australian National University, ACT 2611 (Australia)

2013-01-20

We show, using global three-dimensional grid-based hydrodynamical simulations, that ultrafast outflows (UFOs) from active galactic nuclei (AGNs) result in considerable feedback of energy and momentum into the interstellar medium (ISM) of the host galaxy. The AGN wind interacts strongly with the inhomogeneous, two-phase ISM consisting of dense clouds embedded in a tenuous, hot, hydrostatic medium. The outflow floods through the intercloud channels, sweeps up the hot ISM, and ablates and disperses the dense clouds. The momentum of the UFO is primarily transferred to the dense clouds via the ram pressure in the channel flow, and the wind-blown bubble evolves in the energy-driven regime. Any dependence on UFO opening angle disappears after the first interaction with obstructing clouds. On kpc scales, therefore, feedback by UFOs operates similarly to feedback by relativistic AGN jets. Negative feedback is significantly stronger if clouds are distributed spherically rather than in a disk. In the latter case, the turbulent backflow of the wind drives mass inflow toward the central black hole. Considering the common occurrence of UFOs in AGNs, they are likely to be important in the cosmological feedback cycles of galaxy formation.

ULTRAFAST OUTFLOWS: GALAXY-SCALE ACTIVE GALACTIC NUCLEUS FEEDBACK

International Nuclear Information System (INIS)

Wagner, A. Y.; Umemura, M.; Bicknell, G. V.

2013-01-01

We show, using global three-dimensional grid-based hydrodynamical simulations, that ultrafast outflows (UFOs) from active galactic nuclei (AGNs) result in considerable feedback of energy and momentum into the interstellar medium (ISM) of the host galaxy. The AGN wind interacts strongly with the inhomogeneous, two-phase ISM consisting of dense clouds embedded in a tenuous, hot, hydrostatic medium. The outflow floods through the intercloud channels, sweeps up the hot ISM, and ablates and disperses the dense clouds. The momentum of the UFO is primarily transferred to the dense clouds via the ram pressure in the channel flow, and the wind-blown bubble evolves in the energy-driven regime. Any dependence on UFO opening angle disappears after the first interaction with obstructing clouds. On kpc scales, therefore, feedback by UFOs operates similarly to feedback by relativistic AGN jets. Negative feedback is significantly stronger if clouds are distributed spherically rather than in a disk. In the latter case, the turbulent backflow of the wind drives mass inflow toward the central black hole. Considering the common occurrence of UFOs in AGNs, they are likely to be important in the cosmological feedback cycles of galaxy formation.

Iro/IRX transcription factors negatively regulate Dpp/TGF-β pathway activity during intestinal tumorigenesis.

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Martorell, Òscar; Barriga, Francisco M; Merlos-Suárez, Anna; Stephan-Otto Attolini, Camille; Casanova, Jordi; Batlle, Eduard; Sancho, Elena; Casali, Andreu

2014-11-01

Activating mutations in Wnt and EGFR/Ras signaling pathways are common in colorectal cancer (CRC). Remarkably, clonal co-activation of these pathways in the adult Drosophila midgut induces "tumor-like" overgrowths. Here, we show that, in these clones and in CRC cell lines, Dpp/TGF-β acts as a tumor suppressor. Moreover, we discover that the Iroquois/IRX-family-protein Mirror downregulates the transcription of core components of the Dpp pathway, reducing its tumor suppressor activity. We also show that this genetic interaction is conserved in human CRC cells, where the Iro/IRX proteins IRX3 and IRX5 diminish the response to TGF-β. IRX3 and IRX5 are upregulated in human adenomas, and their levels correlate inversely with the gene expression signature of response to TGF-β. In addition, Irx5 expression confers a growth advantage in the presence of TGF-β, but is selected against in its absence. Together, our results identify a set of Iro/IRX proteins as conserved negative regulators of Dpp/TGF-β activity. We propose that during the characteristic adenoma-to-carcinoma transition of human CRC, the activity of IRX proteins could reduce the sensitivity to the cytostatic effect of TGF-β, conferring a growth advantage to tumor cells prior to the acquisition of mutations in TGF-β pathway components. © 2014 The Authors.

Relational interaction in occupational therapy: Conversation analysis of positive feedback.

Science.gov (United States)

Weiste, Elina

2018-01-01

The therapeutic relationship is an important factor for good therapy outcomes. The primary mediator of a beneficial therapy relationship is clinician-client interaction. However, few studies identify the observable interactional attributes of good quality relational interactions, e.g. offering the client positive feedback. The present paper aims to expand current understanding of relational interaction by analyzing the real-time interactional practices therapists use for offering positive feedback, an important value in occupational therapy. The analysis is based on the conversation analysis of 15 video-recorded occupational therapy encounters in psychiatric outpatient clinics. Two types of positive feedback were identified. In aligning feedback, therapists encouraged and complimented clients' positive perspectives on their own achievements in adopting certain behaviour, encouraging and supporting their progress. In redirecting feedback, therapists shifted the perspective from clients' negative experiences to their positive experiences. This shift was interactionally successful if they laid the foundation for the shift in perspective and attuned their expressions to the clients' emotional states. Occupational therapists routinely provide their clients with positive feedback. Awareness of the interactional attributes related to positive feedback is critically important for successful relational interaction.

Ombud’s Corner: the gift of feedback (part 2)

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Sudeshna Datta-Cockerill

2016-01-01

“When feedback is specific and timely, and also accompanied by a genuinely positive intention, it may be considered to be a gift”. This was the concluding message of the article in the last Bulletin. But how can negative feedback be perceived as an appreciated and useful gift?   As discussed in the previous article, delivering meaningful and effective feedback is an art, and as such, it may also be considered a duty for supervisors, in particular, to invest in honing their skills in order to achieve this aim without triggering demotivation or frustration in their supervisees. But the feedback loop is a two-way process, and requires an open mind on the receiving end in order to be truly useful. If delivered in a constructive and respectful way, feedback can provide us with important clues as to our own possible weaknesses and point us towards ways in which to develop and grow professionally. However, for it to be truly effective, it is up to each of us to hold back our initial ...

Motivation and emotion predict medical students' attention to computer-based feedback.

Science.gov (United States)

Naismith, Laura M; Lajoie, Susanne P

2017-12-14

Students cannot learn from feedback unless they pay attention to it. This study investigated relationships between the personal factors of achievement goal orientations, achievement emotions, and attention to feedback in BioWorld, a computer environment for learning clinical reasoning. Novice medical students (N = 28) completed questionnaires to measure their achievement goal orientations and then thought aloud while solving three endocrinology patient cases and reviewing corresponding expert solutions. Questionnaires administered after each case measured participants' experiences of five feedback emotions: pride, relief, joy, shame, and anger. Attention to individual text segments of the expert solutions was modelled using logistic regression and the method of generalized estimating equations. Participants did not attend to all of the feedback that was available to them. Performance-avoidance goals and shame positively predicted attention to feedback, and performance-approach goals and relief negatively predicted attention to feedback. Aspects of how the feedback was displayed also influenced participants' attention. Findings are discussed in terms of their implications for educational theory as well as the design and use of computer learning environments in medical education.

The homeodomain-leucine zipper (HD-Zip) class I transcription factors ATHB7 and ATHB12 modulate abscisic acid signalling by regulating protein phosphatase 2C and abscisic acid receptor gene activities.

Science.gov (United States)

Valdés, Ana Elisa; Overnäs, Elin; Johansson, Henrik; Rada-Iglesias, Alvaro; Engström, Peter

2012-11-01

Plants perceiving drought activate multiple responses to improve survival, including large-scale alterations in gene expression. This article reports on the roles in the drought response of two Arabidopsis thaliana homeodomain-leucine zipper class I genes; ATHB7 and ATHB12, both strongly induced by water-deficit and abscisic acid (ABA). ABA-mediated transcriptional regulation of both genes is shown to depend on the activity of protein phosphatases type 2C (PP2C). ATHB7 and ATHB12 are, thus, targets of the ABA signalling mechanism defined by the PP2Cs and the PYR/PYL family of ABA receptors, with which the PP2C proteins interact. Our results from chromatin immunoprecipitation and gene expression analyses demonstrate that ATHB7 and ATHB12 act as positive transcriptional regulators of PP2C genes, and thereby as negative regulators of abscisic acid signalling. In support of this notion, our results also show that ATHB7 and ATHB12 act to repress the transcription of genes encoding the ABA receptors PYL5 and PYL8 in response to an ABA stimulus. In summary, we demonstrate that ATHB7 and ATHB12 have essential functions in the primary response to drought, as mediators of a negative feedback effect on ABA signalling in the plant response to water deficit.

Effects of a Video-Feedback Intervention on Teachers' Use of Praise

Science.gov (United States)

Pinter, Erika Blood; East, Allison; Thrush, Nicole

2015-01-01

The purpose of this study was to examine the effects of a video-feedback intervention on the frequency of teachers' use of (a) general group praise, (b) general individual praise, (c) specific group praise, (d) specific individual praise, (e) negative comments directed toward the entire class, and (f) negative comments directed toward an…

Reduction of the elevator illusion from continued hypergravity exposure and visual error-corrective feedback

Science.gov (United States)

Welch, R. B.; Cohen, M. M.; DeRoshia, C. W.

1996-01-01

Ten subjects served as their own controls in two conditions of continuous, centrifugally produced hypergravity (+2 Gz) and a 1-G control condition. Before and after exposure, open-loop measures were obtained of (1) motor control, (2) visual localization, and (3) hand-eye coordination. During exposure in the visual feedback/hypergravity condition, subjects received terminal visual error-corrective feedback from their target pointing, and in the no-visual feedback/hypergravity condition they pointed open loop. As expected, the motor control measures for both experimental conditions revealed very short lived underreaching (the muscle-loading effect) at the outset of hypergravity and an equally transient negative aftereffect on returning to 1 G. The substantial (approximately 17 degrees) initial elevator illusion experienced in both hypergravity conditions declined over the course of the exposure period, whether or not visual feedback was provided. This effect was tentatively attributed to habituation of the otoliths. Visual feedback produced a smaller additional decrement and a postexposure negative after-effect, possible evidence for visual recalibration. Surprisingly, the target-pointing error made during hypergravity in the no-visual-feedback condition was substantially less than that predicted by subjects' elevator illusion. This finding calls into question the neural outflow model as a complete explanation of this illusion.

Soil feedback and pathogen activity in Prunus serotina throughout its native range

NARCIS (Netherlands)

Reinhart, K.O.; Royo, A.A.; Putten, van der W.H.; Clay, K.

2005-01-01

1 Oomycete soil pathogens are known to have a negative effect on Prunus serotina seedling establishment and to promote tree diversity in a deciduous forest in Indiana, USA. Here, we investigate whether negative feedbacks operate widely in its native range in eastern USA. 2 In laboratory experiments,

Direct Transcriptional Consequences of Somatic Mutation in Breast Cancer

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Adam Shlien

2016-08-01

Full Text Available Disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription, coordinated secondary pathway alterations, and increased transcriptional noise. To catalog the rules governing how somatic mutation exerts direct transcriptional effects, we developed an exhaustive pipeline for analyzing RNA sequencing data, which we integrated with whole genomes from 23 breast cancers. Using X-inactivation analyses, we found that cancer cells are more transcriptionally active than intermixed stromal cells. This is especially true in estrogen receptor (ER-negative tumors. Overall, 59% of substitutions were expressed. Nonsense mutations showed lower expression levels than expected, with patterns characteristic of nonsense-mediated decay. 14% of 4,234 rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusions, and premature polyadenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data reveals the rules by which transcriptional machinery interprets somatic mutation.

Resolving Early Signaling Events in T-Cell Activation Leading to IL-2 and FOXP3 Transcription

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Jeffrey P. Perley

2014-11-01

Full Text Available Signal intensity and feedback regulation are known to be major factors in the signaling events stemming from the T-cell receptor (TCR and its various coreceptors, but the exact nature of these relationships remains in question. We present a mathematical model of the complex signaling network involved in T-cell activation with cross-talk between the Erk, calcium, PKC and mTOR signaling pathways. The model parameters are adjusted to fit new and published data on TCR trafficking, Zap70, calcium, Erk and Isignaling. The regulation of the early signaling events by phosphatases, CD45 and SHP1, and the TCR dynamics are critical to determining the behavior of the model. Additional model corroboration is provided through quantitative and qualitative agreement with experimental data collected under different stimulating and knockout conditions. The resulting model is analyzed to investigate how signal intensity and feedback regulation affect TCR- and coreceptor-mediated signal transduction and their downstream transcriptional profiles to predict the outcome for a variety of stimulatory and knockdown experiments. Analysis of the model shows that: (1 SHP1 negative feedback is necessary for preventing hyperactivity in TCR signaling; (2 CD45 is required for TCR signaling, but also partially suppresses it at high expression levels; and (3 elevated FOXP3 and reduced IL-2 signaling, an expression profile often associated with T regulatory cells (Tregs, is observed when the system is subjected to weak TCR and CD28 costimulation or a severe reduction in CD45 activity.

Dynamic Mesoscale Land-Atmosphere Feedbacks in Fragmented Forests in Amazonia

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Rastogi, D.; Baidya Roy, S.

2011-12-01

This paper investigates land-atmosphere feedbacks in disturbed rainforests of Amazonia. Deforestation along the rapidly expanding highways and road network has created the unique fishbone land cover pattern in Rondonia, a state in southwestern Amazonia. Numerical experiments and observations show that sharp gradients in land cover due to the fishbone heterogeneity triggers mesoscale circulations. These circulations significantly change the spatial pattern of local hydrometeorology, especially convection, clouds and precipitation. The primary research question now is can these changes in local hydrometeorology affect vegetation growth in the clearings. If so, that would be a clear indication that land-atmosphere feedbacks can affect vegetation recovery in fragmented forests. A computationally-efficient modeling tool consisting of a mesoscale atmospheric model dynamically coupled with a plant growth model has been specifically developed to identify the atmospheric feedback pathways. Preliminary experiments focus on the seasonal-scale feedbacks during the dry season. Results show that temperature, incoming shortwave and precipitation are the three primary drivers through which the feedbacks operate. Increasing temperature increases respiratory losses generating a positive feedback. Increased cloud cover reduces incoming PAR and photosynthesis, resulting in a positive feedback. Increased precipitation reduces water stress and promotes growth resulting in a negative feedback. The net effect is a combination of these 3 feedback loops. These findings can significantly improve our understanding of ecosystem resiliency in disturbed tropical forests.

Personalised feedback and eco-driving: An explorative study

NARCIS (Netherlands)

Brouwer, R.F.T.; Stuiver, A.; Hof, T.; Kroon, L.; Pauwelussen, J.; Holleman, B.

2015-01-01

Conventional road transport has negative impact on the environment. Stimulating eco-driving through feedback to the driver about his/her energy conservation performance has the potential to reduce CO2 emissions and promote fuel cost savings. Not all drivers respond well to the same type

Damping of resistive instability in UNK-1 with digital electronics in feedback

International Nuclear Information System (INIS)

Zhabitskij, V.M.; Ivanov, I.N.; Korenev, I.L.; Yudin, L.A.

1991-01-01

The basis of resistive instability damper system for the UNK-1 is obtained. The system for each of two directions of beam transverse oscillations includes two pairs of pick-up electrodes and damping kickers connected by delayed negative feedback with digital electronics. The requirements for digital electronics in feedback are discussed. The influence of a notch filter is under consideration. In turns out that a 0.8 MHz feedback system damps the resistive instability in the UNK-1 with increment of 0.7 revolution frequency (for low frequencies). 7 refs.; 8 figs

Effects of dopamine medication on sequence learning with stochastic feedback in Parkinson's disease

Directory of Open Access Journals (Sweden)

Moonsang Seo

2010-08-01

Full Text Available A growing body of evidence suggests that the midbrain dopamine system plays a key role in reinforcement learning and disruption of the midbrain dopamine system in Parkinson's disease (PD may lead to deficits on tasks that require learning from feedback. We examined how changes in dopamine levels (‘ON’ and ‘OFF’ their dopamine medication affect sequence learning from stochastic positive and negative feedback using Bayesian reinforcement learning models. We found deficits in sequence learning in patients with PD when they were ‘ON’ and ‘OFF’ medication relative to healthy controls, but smaller differences between patients ‘OFF’ and ‘ON’. The deficits were mainly due to decreased learning from positive feedback, although across all participant groups learning was more strongly associated with positive than negative feedback in our task. The learning in our task is likely mediated by the relatively depleted dorsal striatum and not the relatively intact ventral striatum. Therefore, the changes we see in our task may be due to a strong loss of phasic dopamine signals in the dorsal striatum in PD.

Effects of Dopamine Medication on Sequence Learning with Stochastic Feedback in Parkinson's Disease

Science.gov (United States)

Seo, Moonsang; Beigi, Mazda; Jahanshahi, Marjan; Averbeck, Bruno B.

2010-01-01

A growing body of evidence suggests that the midbrain dopamine system plays a key role in reinforcement learning and disruption of the midbrain dopamine system in Parkinson's disease (PD) may lead to deficits on tasks that require learning from feedback. We examined how changes in dopamine levels (“ON” and “OFF” their dopamine medication) affect sequence learning from stochastic positive and negative feedback using Bayesian reinforcement learning models. We found deficits in sequence learning in patients with PD when they were “ON” and “OFF” medication relative to healthy controls, but smaller differences between patients “OFF” and “ON”. The deficits were mainly due to decreased learning from positive feedback, although across all participant groups learning was more strongly associated with positive than negative feedback in our task. The learning in our task is likely mediated by the relatively depleted dorsal striatum and not the relatively intact ventral striatum. Therefore, the changes we see in our task may be due to a strong loss of phasic dopamine signals in the dorsal striatum in PD. PMID:20740077

Self-Affirmation Theory and Performance Feedback: When Scoring High Makes You Feel Low.

Science.gov (United States)

Velez, John A; Hanus, Michael D

2016-12-01

Video games have a wide variety of benefits for players. The current study examines how video games can also increase players' willingness to internalize important but threatening self-information. Research suggests that negative information regarding a valued self-image evokes defensive strategies aimed at dismissing or discrediting the source of information. Self-Affirmation Theory proposes that affirming or bolstering an important self-image unrelated to the previous threat can be an effective strategy for reducing defensiveness. Participants in the current study completed a fictitious intelligence test and received negative or no feedback, followed by 15 minutes of video game play that resulted in positive or no feedback. Results suggest that participants who valued video game success as part of their identity exhibited less defensive strategies in the form of increased test credibility ratings and lower self-perceptions of intelligence. This suggests that performing well on a video game is an affirmational resource for players whose identities are contingent upon such success. However, results also indicate that players who did not value video game success but received positive video game feedback exhibited more defensive reactions to the negative intelligence test feedback. This suggests that while players who value video game success as part of their identity may reap benefits from video game play after a self-threat, those who do not value such success may experience more harmful effects.

Grid-Current-Feedback Active Damping for LCL Resonance in Grid-Connected Voltage-Source Converters

DEFF Research Database (Denmark)

Wang, Xiongfei; Blaabjerg, Frede; Loh, Poh Chiang

2016-01-01

This paper investigates active damping of LCL-filter resonance in a grid-connected voltage-source converter with only grid-current feedback control. Basic analysis in the s-domain shows that the proposed damping technique with a negative high-pass filter along its damping path is equivalent...... of phase-lag, in turn, helps to shrink the region of nonminimum-phase behavior caused by negative virtual resistance inserted unintentionally by most digitally implemented active damping techniques. The presented high-pass-filtered active damping technique with a single grid-current feedback loop is thus...

Controlling a negative loaded hydraulic cylinder using pressure feedback

DEFF Research Database (Denmark)

Hansen, M.R.; Andersen, T.O.

2010-01-01

This paper is concerned with the inherent oscillatory nature of pressure compensated velocity control of a hydraulic cylinder subjected to a negative load and suspended by means of an over-center valve. Initially, a linearized stability analysis of such a hydraulic circuit is carried out clearly ...... in a nonlinear time domain simulation model validating the linear stability analysis....

C'est le Ton Qui Fait la Critique—for the powerful: the effects of feedback framing and power on affective reactions

NARCIS (Netherlands)

Niemann, Jana; Wisse, Barbara; Rus, Diana; Van Yperen, Nico W.; Sassenberg, Kai

2014-01-01

Although negative feedback is usually provided with the best of intentions, it often causes unfavorable affective reactions in the receiver such as anger and shame. The purpose of the present research is to identify factors that may attenuate or intensify these reactions to negative feedback. We

Strategies in probabilistic feedback learning in Parkinson patients OFF medication.

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Bellebaum, C; Kobza, S; Ferrea, S; Schnitzler, A; Pollok, B; Südmeyer, M

2016-04-21

Studies on classification learning suggested that altered dopamine function in Parkinson's Disease (PD) specifically affects learning from feedback. In patients OFF medication, enhanced learning from negative feedback has been described. This learning bias was not seen in observational learning from feedback, indicating different neural mechanisms for this type of learning. The present study aimed to compare the acquisition of stimulus-response-outcome associations in PD patients OFF medication and healthy control subjects in active and observational learning. 16 PD patients OFF medication and 16 controls were examined with three parallel learning tasks each, two feedback-based (active and observational) and one non-feedback-based paired associates task. No acquisition deficit was seen in the patients for any of the tasks. More detailed analyses on the learning strategies did, however, reveal that the patients showed more lose-shift responses during active feedback learning than controls, and that lose-shift and win-stay responses more strongly determined performance accuracy in patients than controls. For observational feedback learning, the performance of both groups correlated similarly with the performance in non-feedback-based paired associates learning and with the accuracy of observed performance. Also, patients and controls showed comparable evidence of feedback processing in observational learning. In active feedback learning, PD patients use alternative learning strategies than healthy controls. Analyses on observational learning did not yield differences between patients and controls, adding to recent evidence of a differential role of the human striatum in active and observational learning from feedback. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Reducing negative affect and increasing rapport improve interracial mentorship outcomes.

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Leitner, Jordan B; Ayduk, Özlem; Boykin, C Malik; Mendoza-Denton, Rodolfo

2018-01-01

Research suggests that interracial mentoring relationships are strained by negative affect and low rapport. As such, it stands to reason that strategies that decrease negative affect and increase rapport should improve these relationships. However, previous research has not tested this possibility. In video-chats (Studies 1 and 2) and face-to-face meetings (Study 3), we manipulated the degree of mutual self-disclosure between mentees and mentors, a strategy that has been shown to reduce negative affect and increase rapport. We then measured negative affect and rapport as mediators, and mentee performance (quality of speech delivered; Studies 1 and 3) and mentor performance (warmth and helpfulness; Studies 2 and 3) as key outcomes. Results revealed that increased self-disclosure decreased negative affect and increased rapport for both mentees and mentors. Among mentees, decreased negative affect predicted better performance (Studies 1 and 3). Among mentors, increased rapport predicted warmer feedback (Studies 2 and 3). These effects remained significant when we meta-analyzed data across studies (Study 4), and also revealed the relationship of rapport to more helpful feedback. Findings suggest that affect and rapport are key features in facilitating positive outcomes in interracial mentoring relationships.

A novel branched chain amino acids responsive transcriptional regulator, BCARR, negatively acts on the proteolytic system in Lactobacillus helveticus.

Directory of Open Access Journals (Sweden)

Taketo Wakai

Full Text Available Transcriptional negative regulation of the proteolytic system of Lactobacillus helveticus CM4 in response to amino acids seems to be very important for the control of antihypertensive peptide production; however, it remains poorly understood. A 26-kDa protein with N-terminal cystathionine β-synthase domains (CBS domain protein, which seems to be involved in the regulatory system, was purified by using a DNA-sepharose bound 300-bp DNA fragment corresponding to the upstream regions of the six proteolytic genes that are down-regulated by amino acids. The CBS domain protein bound to a DNA fragment corresponding to the region upstream of the pepV gene in response to branched chain amino acids (BCAAs. The expression of the pepV gene in Escherichia coli grown in BCAA-enriched medium was repressed when the CBS domain protein was co-expressed. These results reveal that the CBS domain protein acts as a novel type of BCAA-responsive transcriptional regulator (BCARR in L. helveticus. From comparative analysis of the promoter regions of the six proteolysis genes, a palindromic AT-rich motif, 5'-AAAAANNCTWTTATT-3', was predicted as the consensus DNA motif for the BCARR protein binding. Footprint analysis using the pepV promotor region and gel shift analyses with the corresponding short DNA fragments strongly suggested that the BCARR protein binds adjacent to the pepV promoter region and affects the transcription level of the pepV gene in the presence of BCAAs. Homology search analysis of the C-terminal region of the BCARR protein suggested the existence of a unique βαββαβ fold structure that has been reported in a variety of ACT (aspartate kinase-chorismate mutase-tyrA domain proteins for sensing amino acids. These results also suggest that the sensing of BCAAs by the ACT domain might promote the binding of the BCARR to DNA sequences upstream of proteolysis genes, which affects the gene expression of the proteolytic system in L. helveticus.

Selection Shapes Transcriptional Logic and Regulatory Specialization in Genetic Networks.

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Fogelmark, Karl; Peterson, Carsten; Troein, Carl

2016-01-01

Living organisms need to regulate their gene expression in response to environmental signals and internal cues. This is a computational task where genes act as logic gates that connect to form transcriptional networks, which are shaped at all scales by evolution. Large-scale mutations such as gene duplications and deletions add and remove network components, whereas smaller mutations alter the connections between them. Selection determines what mutations are accepted, but its importance for shaping the resulting networks has been debated. To investigate the effects of selection in the shaping of transcriptional networks, we derive transcriptional logic from a combinatorially powerful yet tractable model of the binding between DNA and transcription factors. By evolving the resulting networks based on their ability to function as either a simple decision system or a circadian clock, we obtain information on the regulation and logic rules encoded in functional transcriptional networks. Comparisons are made between networks evolved for different functions, as well as with structurally equivalent but non-functional (neutrally evolved) networks, and predictions are validated against the transcriptional network of E. coli. We find that the logic rules governing gene expression depend on the function performed by the network. Unlike the decision systems, the circadian clocks show strong cooperative binding and negative regulation, which achieves tight temporal control of gene expression. Furthermore, we find that transcription factors act preferentially as either activators or repressors, both when binding multiple sites for a single target gene and globally in the transcriptional networks. This separation into positive and negative regulators requires gene duplications, which highlights the interplay between mutation and selection in shaping the transcriptional networks.

What does patient feedback reveal about the NHS? A mixed methods study of comments posted to the NHS Choices online service

Science.gov (United States)

Brookes, Gavin; Baker, Paul

2017-01-01

Objective To examine the key themes of positive and negative feedback in patients’ online feedback on NHS (National Health Service) services in England and to understand the specific issues within these themes and how they drive positive and negative evaluation. Design Computer-assisted quantitative and qualitative studies of 228 113 comments (28 971 142 words) of online feedback posted to the NHS Choices website. Comments containing the most frequent positive and negative evaluative words are qualitatively examined to determine the key drivers of positive and negative feedback. Participants Contributors posting comments about the NHS between March 2013 and September 2015. Results Overall, NHS services were evaluated positively approximately three times more often than negatively. The four key areas of focus were: treatment, communication, interpersonal skills and system/organisation. Treatment exhibited the highest proportion of positive evaluative comments (87%), followed by communication (77%), interpersonal skills (44%) and, finally, system/organisation (41%). Qualitative analysis revealed that reference to staff interpersonal skills featured prominently, even in comments relating to treatment and system/organisational issues. Positive feedback was elicited in cases of staff being caring, compassionate and knowing patients’’ names, while rudeness, apathy and not listening were frequent drivers of negative feedback. Conclusions Although technical competence constitutes an undoubtedly fundamental aspect of healthcare provision, staff members were much more likely to be evaluated both positively and negatively according to their interpersonal skills. Therefore, the findings reported in this study highlight the salience of such ‘soft’ skills to patients and emphasise the need for these to be focused upon and developed in staff training programmes, as well as ensuring that decisions around NHS funding do not result in demotivated and rushed staff. The

Inter-annual variabilities in biogeophysical feedback of terrestrial ecosystem to atmosphere using a land surface model

Science.gov (United States)

Seo, C.; Hong, S.; Jeong, H. M.; Jeon, J.

2017-12-01

Biogeophysical processes of terrestrial ecosystem such as water vapor and energy flux are the key features to understand ecological feedback to atmospheric processes and thus role of terrestrial ecosystem in climate system. For example, it has been recently known that the ecological feedback through water vapor and energy flux results in regulating regional weathers and climates which is one of the fundamental functions of terrestrial ecosystem. In regional scale, water vapor flux has been known to give negative feedback to atmospheric warming, while energy flux from the surface has been known to positive feedback. In this study, we explored the inter-annual variabilities in these two biogeophysical features to see how the climate regulating functions of terrestrial ecosystem have been changed with climate change. We selected a land surface model involving vegetation dynamics that is forced by atmospheric data from NASA including precipitation, temperature, wind, surface pressure, humidity, and incoming radiations. From the land surface model, we simulated 60-year water vapor and energy fluxes from 1961 to 2010, and calculates feedbacks of terrestrial ecosystem as in radiation amount into atmosphere. Then, we analyzed the inter-annual variabilities in the feedbacks. The results showed that some mid-latitude areas showing very high variabilities in precipitation showed higher positive feedback and/or lower negative feedback. These results suggest deterioration of the biogeophyisical factor of climate regulating function over those regions.

Pubertal Escape From Estradiol Negative Feedback in Ewe Lambs Is Not Accounted for by Decreased ESR1 mRNA or Protein in Kisspeptin Neurons.

Science.gov (United States)

Bedenbaugh, Michelle N; D'Oliveira, Marcella; Cardoso, Rodolfo C; Hileman, Stanley M; Williams, Gary L; Amstalden, Marcel

2018-01-01

In this study, we investigated whether decreased sensitivity to estradiol negative feedback is associated with reduced estrogen receptor α (ESR1) expression in kisspeptin neurons as ewe lambs approach puberty. Lambs were ovariectomized and received no implant (OVX) or an implant containing estradiol (OVX+E). In the middle arcuate nucleus (mARC), ESR1 messenger RNA (mRNA) was greater in OVX than OVX+E lambs but did not differ elsewhere. Post hoc analysis of luteinizing hormone (LH) secretion from OVX+E lambs revealed three patterns of LH pulsatility: low [1 to 2 pulses per 12 hours; low frequency (LF), n = 3], moderate [6 to 7 pulses per 12 hours; moderate frequency (MF), n = 6], and high [>10 pulses per 12 hours; high frequency (HF), n = 5]. The percentage of kisspeptin neurons containing ESR1 mRNA in the preoptic area did not differ among HF, MF, or LF groups. However, the percentage of kisspeptin neurons containing ESR1 mRNA in the mARC was greater in HF (57%) than in MF (36%) or LF (27%) lambs and did not differ from OVX (50%) lambs. A higher percentage of kisspeptin neurons contained ESR1 protein in all regions of the arcuate nucleus (ARC) in OVX compared with OVX+E lambs. There were no differences in ESR1 protein among the HF, MF, or LF groups in the preoptic area or ARC. Contrary to our hypothesis, increases in LH pulsatility were associated with enhanced ESR1 mRNA abundance in kisspeptin neurons in the ARC, and absence of estradiol increased the percentage of kisspeptin neurons containing ESR1 protein in the ARC. Therefore, changes in the expression of ESR1, particularly in kisspeptin neurons in the ARC, do not explain the pubertal escape from estradiol negative feedback in ewe lambs. Copyright © 2018 Endocrine Society.

A simple reactivity feedback model accounting for radial core expansion effects in the liquid metal fast reactor

International Nuclear Information System (INIS)

Kwon, Young Min; Lee, Yong Bum; Chang, Won Pyo; Haha, Do Hee

2002-01-01

The radial core expansion due to the structure temperature rise is one of major negative reactivity insertion mechanisms in metallic fueled reactor. Thermal expansion is a result of both the laws of nature and the particular core design and it causes negative reactivity feedback by the combination of increased core volume captures and increased core surface leakage. The simple radial core expansion reactivity feedback model developed for the SSC-K code was evaluated by the code-to-code comparison analysis. From the comparison results, it can be stated that the radial core expansion reactivity feedback model employed into the SSC-K code may be reasonably accurate in the UTOP analysis

A simple reactivity feedback model accounting for radial core expansion effects in the liquid metal fast reactor

Energy Technology Data Exchange (ETDEWEB)

Kwon, Young Min; Lee, Yong Bum; Chang, Won Pyo; Haha, Do Hee [KAERI, Taejon (Korea, Republic of)

2002-10-01

The radial core expansion due to the structure temperature rise is one of major negative reactivity insertion mechanisms in metallic fueled reactor. Thermal expansion is a result of both the laws of nature and the particular core design and it causes negative reactivity feedback by the combination of increased core volume captures and increased core surface leakage. The simple radial core expansion reactivity feedback model developed for the SSC-K code was evaluated by the code-to-code comparison analysis. From the comparison results, it can be stated that the radial core expansion reactivity feedback model employed into the SSC-K code may be reasonably accurate in the UTOP analysis.

A conceptual framework for understanding leader selfschemas and the influence of those self-schemas on the integration of feedback

Directory of Open Access Journals (Sweden)

J.W. (Cobus Pienaar

2017-03-01

Full Text Available Orientation: Recently, the importance of blind spots, derailments and failures of leaders have been in the spotlight. Enhancing their levels of self-awareness is one of the steps leaders can take to avoid derailment. While it promotes self-awareness and decreases leadership blind spots, feedback is also considered one of the most effective tools available to modify behaviour. Researchers and practitioners are encouraged to explore the individual characteristics that will enhance or impede the feedback received from others so as to bring about behavioural change and increased levels of self-awareness. Motivation for the study: The aim of this theoretical article was to consider various conceptual frameworks and literature in an endeavour to illustrate how leaders’ self-schemas might explain the underlying reasons why some leaders are more likely to receive, integrate, assimilate and act on the feedback, while others are not, based on how they see themselves in relation to others. Research design, approach and method: A literature-based method was utilised for this study in order to provide a critical analysis of the available literature and illustrate the different theoretical perspectives and underpinnings. Practical/managerial implications: Leaders who are more likely to consider feedback and/or ask for feedback from others seem to be less prone to develop a blind spot and will therefore have a more accurate view of themselves. Those who have an over-rating of themselves are unlikely to have an accurate view of themselves. In an attempt to ‘protect’ this inflated view, such individuals will be less open to negative feedback, as it may challenge their own perspectives and opinions they hold of themselves. Individuals who hold an overly negative view of themselves are more likely to reject positive feedback and less likely to request or accept positive feedback as it may contradict the viewpoint they hold of themselves. They may however be

Audio Feedback -- Better Feedback?

Science.gov (United States)

Voelkel, Susanne; Mello, Luciane V.

2014-01-01

National Student Survey (NSS) results show that many students are dissatisfied with the amount and quality of feedback they get for their work. This study reports on two case studies in which we tried to address these issues by introducing audio feedback to one undergraduate (UG) and one postgraduate (PG) class, respectively. In case study one…

Consequences of changes in vegetation and snow cover for climate feedbacks in Alaska and northwest Canada

Science.gov (United States)

Euskirchen, Eugénie S.; Bennett, A. P.; Breen, Amy L.; Genet, Helene; Lindgren, Michael A.; Kurkowski, Tom; McGuire, A. David; Rupp, T. Scott

2016-01-01

Changes in vegetation and snow cover may lead to feedbacks to climate through changes in surface albedo and energy fluxes between the land and atmosphere. In addition to these biogeophysical feedbacks, biogeochemical feedbacks associated with changes in carbon (C) storage in the vegetation and soils may also influence climate. Here, using a transient biogeographic model (ALFRESCO) and an ecosystem model (DOS-TEM), we quantified the biogeophysical feedbacks due to changes in vegetation and snow cover across continuous permafrost to non-permafrost ecosystems in Alaska and northwest Canada. We also computed the changes in carbon storage in this region to provide a general assessment of the direction of the biogeochemical feedback. We considered four ecoregions, or Landscape Conservations Cooperatives (LCCs; including the Arctic, North Pacific, Western Alaska, and Northwest Boreal). We examined the 90 year period from 2010 to 2099 using one future emission scenario (A1B), under outputs from two general circulation models (MPI-ECHAM5 and CCCMA-CGCM3.1). We found that changes in snow cover duration, including both the timing of snowmelt in the spring and snow return in the fall, provided the dominant positive biogeophysical feedback to climate across all LCCs, and was greater for the ECHAM (+3.1 W m−2 decade−1regionally) compared to the CCCMA (+1.3 W m−2 decade−1 regionally) scenario due to an increase in loss of snow cover in the ECHAM scenario. The greatest overall negative feedback to climate from changes in vegetation cover was due to fire in spruce forests in the Northwest Boreal LCC and fire in shrub tundra in the Western LCC (−0.2 to −0.3 W m−2 decade−1). With the larger positive feedbacks associated with reductions in snow cover compared to the smaller negative feedbacks associated with shifts in vegetation, the feedback to climate warming was positive (total feedback of +2.7 W m−2decade regionally in the ECHAM scenario compared to +0.76 W

Downregulation of IL-12 and a novel negative feedback system mediated by CD25+CD4+ T cells

International Nuclear Information System (INIS)

Sato, Kojiro; Tateishi, Shoko; Kubo, Kanae; Mimura, Toshihide; Yamamoto, Kazuhiko; Kanda, Hiroko

2005-01-01

CD25 + CD4 + regulatory T cells suppress immune responses and are believed to play roles in preventing autoimmune diseases. However, the mechanism(s) underlying the suppression and the regulation of their homeostasis remain to be elucidated. Here we show that these regulatory T cells downregulated CD25 - CD4 + T-cell-mediated production of IL-12 from antigen-presenting cells, which can act as a growth factor for CD25 - CD4 + T cells. We further found that CD25 + CD4 + T cells, despite their well-documented 'anergic' nature, proliferate significantly in vitro only when CD25 - CD4 + T cells are present. Notably, this proliferation was strongly dependent on IL-2 and relatively independent of IL-12. Thus, CD25 + CD4 + T cells suppress CD25 - CD4 + T-cell responses, at least in part, by inhibiting IL-12 production while they themselves can undergo proliferation with the mediation of CD25 - CD4 + T cells in vitro. These results offer a novel negative feedback system involving a tripartite interaction among CD25 + CD4 + and CD25 - CD4 + T cells, and APCs that may contribute to the termination of immune responses

Peer-Assisted Analysis of Resident Feedback Improves Clinical Teaching: A Case Report.

Science.gov (United States)

Mai, Christine L; Baker, Keith

2017-07-01

Anesthesiologists play an important role in educating future clinicians. Yet few residency programs incorporate teaching skills into faculty development. Consequently, many anesthesiologists have limited training to supervise and educate residents. In turn, these attendings may receive negative feedback and poor evaluations from residents without a means to effectively improve. Peer-assisted teaching between faculty members may serve as a strategy to improve teaching skills. We report a case of peer-assisted analysis of resident feedback to identify specific areas of concern that were targeted for improvement. This approach resulted in improved teaching scores and feedback for the faculty member.

The Effects of a Local Negative Feedback Function between Choice and Relative Reinforcer Rate

Science.gov (United States)

Davison, Michael; Elliffe, Douglas; Marr, M. Jackson

2010-01-01

Four pigeons were trained on two-key concurrent variable-interval schedules with no changeover delay. In Phase 1, relative reinforcers on the two alternatives were varied over five conditions from 0.1 to 0.9. In Phases 2 and 3, we instituted a molar feedback function between relative choice in an interreinforcer interval and the probability of…

Imaging stability in force-feedback high-speed atomic force microscopy

International Nuclear Information System (INIS)

Kim, Byung I.; Boehm, Ryan D.

2013-01-01

We studied the stability of force-feedback high-speed atomic force microscopy (HSAFM) by imaging soft, hard, and biological sample surfaces at various applied forces. The HSAFM images showed sudden topographic variations of streaky fringes with a negative applied force when collected on a soft hydrocarbon film grown on a grating sample, whereas they showed stable topographic features with positive applied forces. The instability of HSAFM images with the negative applied force was explained by the transition between contact and noncontact regimes in the force–distance curve. When the grating surface was cleaned, and thus hydrophilic by removing the hydrocarbon film, enhanced imaging stability was observed at both positive and negative applied forces. The higher adhesive interaction between the tip and the surface explains the improved imaging stability. The effects of imaging rate on the imaging stability were tested on an even softer adhesive Escherichia coli biofilm deposited onto the grating structure. The biofilm and planktonic cell structures in HSAFM images were reproducible within the force deviation less than ∼0.5 nN at the imaging rate up to 0.2 s per frame, suggesting that the force-feedback HSAFM was stable for various imaging speeds in imaging softer adhesive biological samples. - Highlights: ► We investigated the imaging stability of force-feedback HSAFM. ► Stable–unstable imaging transitions rely on applied force and sample hydrophilicity. ► The stable–unstable transitions are found to be independent of imaging rate

Regulation of Arabidopsis Early Anther Development by Putative Cell-Cell Signaling Molecules and Transcriptional Regulators

Institute of Scientific and Technical Information of China (English)

Yu-Jin Sun; Carey LH Hord; Chang-Bin Chen; Hong Ma

2007-01-01

Anther development in flowering plants involves the formation of several cell types, including the tapetal and pollen mother cells. The use of genetic and molecular tools has led to the identification and characterization of genes that are critical for normal cell division and differentiation in Arabidopsis early anther development. We review here several recent studies on these genes, including the demonstration that the putative receptor protein kinases BAM1 and BAM2 together play essential roles in the control of early cell division and differentiation. In addition, we discuss the hypothesis that BAM1/2 may form a positive-negative feedback regulatory loop with a previously identified key regulator, SPOROCYTELESS (also called NOZZLE),to control the balance between sporogenous and somatic cell types in the anther. Furthermore, we summarize the isolation and functional analysis of the DYSFUNCTIONAL TAPETUM1 (DYT1) gene in promoting proper tapetal cell differentiation. Our finding that DYT1 encodes a putative transcription factor of the bHLH family, as well as relevant expression analyses, strongly supports a model that DYT1 serves as a critical link between upstream factors and downstream target genes that are critical for normal tapetum development and function. These studies, together with other recently published works, indicate that cell-cell communication and transcriptional control are key processes essential for cell fate specification in anther development.

Effects of Stratospheric Ozone Depletion, Solar UV Radiation, and Climate Change on Biogeochemical Cycling: Interactions and Feedbacks

Science.gov (United States)

Climate change modulates the effects of solar UV radiation on biogeochemical cycles in terrestrial and aquatic ecosystems, particularly for carbon cycling, resulting in UV-mediated positive or negative feedbacks on climate. Possible positive feedbacks discussed in this assessment...

Impaired glucocorticoid-mediated HPA axis negative feedback induced by juvenile social isolation in male rats.

Science.gov (United States)

Boero, Giorgia; Pisu, Maria Giuseppina; Biggio, Francesca; Muredda, Laura; Carta, Gianfranca; Banni, Sebastiano; Paci, Elena; Follesa, Paolo; Concas, Alessandra; Porcu, Patrizia; Serra, Mariangela

2018-05-01

We previously demonstrated that socially isolated rats at weaning showed a significant decrease in corticosterone and adrenocorticotropic hormone (ACTH) levels, associated with an enhanced response to acute stressful stimuli. Here we shown that social isolation decreased levels of total corticosterone and of its carrier corticosteroid-binding globulin, but did not influence the availability of the free active fraction of corticosterone, both under basal conditions and after acute stress exposure. Under basal conditions, social isolation increased the abundance of glucocorticoid receptors, while it decreased that of mineralocorticoid receptors. After acute stress exposure, socially isolated rats showed long-lasting corticosterone, ACTH and corticotrophin releasing hormone responses. Moreover, while in the hippocampus and hypothalamus of group-housed rats glucocorticoid receptors expression increased with time and reached a peak when corticosterone levels returned to basal values, in socially isolated rats expression of glucocorticoid receptors did not change. Finally, social isolation also affected the hypothalamic endocannabinoid system: compared to group-housed rats, basal levels of anandamide and cannabinoid receptor type 1 were increased, while basal levels of 2-arachidonoylglycerol were decreased in socially isolated rats and did not change after acute stress exposure. The present results show that social isolation in male rats alters basal HPA axis activity and impairs glucocorticoid-mediated negative feedback after acute stress. Given that social isolation is considered an animal model of several neuropsychiatric disorders, such as generalized anxiety disorder, depression, post-traumatic stress disorder and schizophrenia, these data could contribute to better understand the alterations in HPA axis activity observed in these disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Proprioceptive feedback and brain computer interface (BCI based neuroprostheses.

Directory of Open Access Journals (Sweden)

Ander Ramos-Murguialday

Full Text Available Brain computer interface (BCI technology has been proposed for motor neurorehabilitation, motor replacement and assistive technologies. It is an open question whether proprioceptive feedback affects the regulation of brain oscillations and therefore BCI control. We developed a BCI coupled on-line with a robotic hand exoskeleton for flexing and extending the fingers. 24 healthy participants performed five different tasks of closing and opening the hand: (1 motor imagery of the hand movement without any overt movement and without feedback, (2 motor imagery with movement as online feedback (participants see and feel their hand, with the exoskeleton moving according to their brain signals, (3 passive (the orthosis passively opens and closes the hand without imagery and (4 active (overt movement of the hand and rest. Performance was defined as the difference in power of the sensorimotor rhythm during motor task and rest and calculated offline for different tasks. Participants were divided in three groups depending on the feedback receiving during task 2 (the other tasks were the same for all participants. Group 1 (n = 9 received contingent positive feedback (participants' sensorimotor rhythm (SMR desynchronization was directly linked to hand orthosis movements, group 2 (n = 8 contingent "negative" feedback (participants' sensorimotor rhythm synchronization was directly linked to hand orthosis movements and group 3 (n = 7 sham feedback (no link between brain oscillations and orthosis movements. We observed that proprioceptive feedback (feeling and seeing hand movements improved BCI performance significantly. Furthermore, in the contingent positive group only a significant motor learning effect was observed enhancing SMR desynchronization during motor imagery without feedback in time. Furthermore, we observed a significantly stronger SMR desynchronization in the contingent positive group compared to the other groups during active and

Proprioceptive feedback and brain computer interface (BCI) based neuroprostheses.

Science.gov (United States)

Ramos-Murguialday, Ander; Schürholz, Markus; Caggiano, Vittorio; Wildgruber, Moritz; Caria, Andrea; Hammer, Eva Maria; Halder, Sebastian; Birbaumer, Niels

2012-01-01

Brain computer interface (BCI) technology has been proposed for motor neurorehabilitation, motor replacement and assistive technologies. It is an open question whether proprioceptive feedback affects the regulation of brain oscillations and therefore BCI control. We developed a BCI coupled on-line with a robotic hand exoskeleton for flexing and extending the fingers. 24 healthy participants performed five different tasks of closing and opening the hand: (1) motor imagery of the hand movement without any overt movement and without feedback, (2) motor imagery with movement as online feedback (participants see and feel their hand, with the exoskeleton moving according to their brain signals, (3) passive (the orthosis passively opens and closes the hand without imagery) and (4) active (overt) movement of the hand and rest. Performance was defined as the difference in power of the sensorimotor rhythm during motor task and rest and calculated offline for different tasks. Participants were divided in three groups depending on the feedback receiving during task 2 (the other tasks were the same for all participants). Group 1 (n = 9) received contingent positive feedback (participants' sensorimotor rhythm (SMR) desynchronization was directly linked to hand orthosis movements), group 2 (n = 8) contingent "negative" feedback (participants' sensorimotor rhythm synchronization was directly linked to hand orthosis movements) and group 3 (n = 7) sham feedback (no link between brain oscillations and orthosis movements). We observed that proprioceptive feedback (feeling and seeing hand movements) improved BCI performance significantly. Furthermore, in the contingent positive group only a significant motor learning effect was observed enhancing SMR desynchronization during motor imagery without feedback in time. Furthermore, we observed a significantly stronger SMR desynchronization in the contingent positive group compared to the other groups during active and passive

Feedback Conversations: Creating Feedback Dialogues with a New Textual Tool for Industrial Design Student Feedback

Science.gov (United States)

Funk, Mathias; van Diggelen, Migchiel

2017-01-01

In this paper, the authors describe how a study of a large database of written university teacher feedback in the department of Industrial Design led to the development of a new conceptual framework for feedback and the design of a new feedback tool. This paper focuses on the translation of related work in the area of feedback mechanisms for…

Feedback on Feedback: Eliciting Learners' Responses to Written Feedback through Student-Generated Screencasts

Science.gov (United States)

Fernández-Toro, María; Furnborough, Concha

2014-01-01

Despite the potential benefits of assignment feedback, learners often fail to use it effectively. This study examines the ways in which adult distance learners engage with written feedback on one of their assignments. Participants were 10 undergraduates studying Spanish at the Open University, UK. Their responses to feedback were elicited by means…

The neural representation of typical and atypical experiences of negative images: comparing fear, disgust and morbid fascination

Science.gov (United States)

Lindquist, Kristen A.; Adebayo, Morenikeji; Barrett, Lisa Feldman

2016-01-01

Negative stimuli do not only evoke fear or disgust, but can also evoke a state of ‘morbid fascination’ which is an urge to approach and explore a negative stimulus. In the present neuroimaging study, we applied an innovative method to investigate the neural systems involved in typical and atypical conceptualizations of negative images. Participants received false feedback labeling their mental experience as fear, disgust or morbid fascination. This manipulation was successful; participants judged the false feedback correct for 70% of the trials on average. The neuroimaging results demonstrated differential activity within regions in the ‘neural reference space for discrete emotion’ depending on the type of feedback. We found robust differences in the ventrolateral prefrontal cortex, the dorsomedial prefrontal cortex and the lateral orbitofrontal cortex comparing morbid fascination to control feedback. More subtle differences in the dorsomedial prefrontal cortex and the lateral orbitofrontal cortex were also found between morbid fascination feedback and the other emotion feedback conditions. This study is the first to forward evidence about the neural representation of the experimentally unexplored state of morbid fascination. In line with a constructionist framework, our findings suggest that neural resources associated with the process of conceptualization contribute to the neural representation of this state. PMID:26180088

Soil feedback and pathogen activity in Prunus serotina throughout its native range

Science.gov (United States)

Kurt O. Reinhart; Alejandro Royo; Wim H. Van der Putten; Keith Clay

2005-01-01

1 Oomycete soil pathogens are known to have a negative effect on Prunus serotina seedling establishment and to promote tree diversity in a deciduous forest in Indiana, USA. Here, we investigate whether negative feedbacks operate widely in its native range in eastern USA. 2 In laboratory experiments, soil sterilization was used to test the...

Overexpression of transcription factor Sp1 leads to gene expression perturbations and cell cycle inhibition.

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Emmanuelle Deniaud

Full Text Available BACKGROUND: The ubiquitous transcription factor Sp1 regulates the expression of a vast number of genes involved in many cellular functions ranging from differentiation to proliferation and apoptosis. Sp1 expression levels show a dramatic increase during transformation and this could play a critical role for tumour development or maintenance. Although Sp1 deregulation might be beneficial for tumour cells, its overexpression induces apoptosis of untransformed cells. Here we further characterised the functional and transcriptional responses of untransformed cells following Sp1 overexpression. METHODOLOGY AND PRINCIPAL FINDINGS: We made use of wild-type and DNA-binding-deficient Sp1 to demonstrate that the induction of apoptosis by Sp1 is dependent on its capacity to bind DNA. Genome-wide expression profiling identified genes involved in cancer, cell death and cell cycle as being enriched among differentially expressed genes following Sp1 overexpression. In silico search to determine the presence of Sp1 binding sites in the promoter region of modulated genes was conducted. Genes that contained Sp1 binding sites in their promoters were enriched among down-regulated genes. The endogenous sp1 gene is one of the most down-regulated suggesting a negative feedback loop induced by overexpressed Sp1. In contrast, genes containing Sp1 binding sites in their promoters were not enriched among up-regulated genes. These results suggest that the transcriptional response involves both direct Sp1-driven transcription and indirect mechanisms. Finally, we show that Sp1 overexpression led to a modified expression of G1/S transition regulatory genes such as the down-regulation of cyclin D2 and the up-regulation of cyclin G2 and cdkn2c/p18 expression. The biological significance of these modifications was confirmed by showing that the cells accumulated in the G1 phase of the cell cycle before the onset of apoptosis. CONCLUSION: This study shows that the binding to DNA

Deciphering Mineral Homeostasis in Barley Seed Transfer Cells at Transcriptional Level.

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Behrooz Darbani

the treatments, indicating metal-affinity shifts among isoforms of metal transporters. Most important, we found the zinc treatment to impair both photosynthesis and respiration. A wide range of transcriptional changes including stress-related genes and negative feedback loops emphasize the importance to withhold mineral contents below certain cellular levels which otherwise might lead to agronomical impeding side-effects. By illustrating new mechanisms, genes, and transcripts, this report provides a solid platform towards understanding the complex network of plant mineral homeostasis.

Deciphering Mineral Homeostasis in Barley Seed Transfer Cells at Transcriptional Level.

Science.gov (United States)

Darbani, Behrooz; Noeparvar, Shahin; Borg, Søren

2015-01-01

, indicating metal-affinity shifts among isoforms of metal transporters. Most important, we found the zinc treatment to impair both photosynthesis and respiration. A wide range of transcriptional changes including stress-related genes and negative feedback loops emphasize the importance to withhold mineral contents below certain cellular levels which otherwise might lead to agronomical impeding side-effects. By illustrating new mechanisms, genes, and transcripts, this report provides a solid platform towards understanding the complex network of plant mineral homeostasis.

Sensitivity analysis of primary resonances and bifurcations of a controlled piecewise-smooth system with negative stiffness

Science.gov (United States)

Huang, Dongmei; Xu, Wei

2017-11-01

In this paper, the combination of the cubic nonlinearity and time delay is proposed to improve the performance of a piecewise-smooth (PWS) system with negative stiffness. Dynamical properties, feedback control performance and symmetry-breaking bifurcation are mainly considered for a PWS system with negative stiffness under nonlinear position and velocity feedback control. For the free vibration system, the homoclinic-like orbits are firstly derived. Then, the amplitude-frequency response of the controlled system is obtained analytically in aspect of the Lindstedt-Poincaré method and the method of multiple scales, which is also verified through the numerical results. In this regard, a softening-type behavior, which directly leads to the multi-valued responses, is illustrated over the negative position feedback. Especially, the five-valued responses in which three branches of them are stable are found. And complex multi-valued characteristics are also observed in the force-amplitude responses. Furthermore, for explaining the effectiveness of feedback control, the equivalent damping and stiffness are also introduced. Sensitivity of the system response to the feedback gain and time delay is comprehensively considered and interesting dynamical properties are found. Relatively, from the perspective of suppressing the maximum amplitude and controlling the resonance stability, the selection of the feedback parameters is discussed. Finally, the symmetry-breaking bifurcation and chaotic motion are considered.

Assessing Whether Students Seek Constructive Criticism: The Design of an Automated Feedback System for a Graphic Design Task

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Cutumisu, Maria; Blair, Kristen P.; Chin, Doris B.; Schwartz, Daniel L.

2017-01-01

We introduce a choice-based assessment strategy that measures students' choices to seek constructive feedback and to revise their work. We present the feedback system of a game we designed to assess whether students choose positive or negative feedback and choose to revise their posters in the context of a poster design task, where they learn…

The Impact of Observed Vegetation Changes on Land–Atmosphere Feedbacks During Drought

KAUST Repository

Meng, X. H.; Evans, J. P.; McCabe, Matthew

2014-01-01

Simulated feedbacks between vegetation fraction, soil moisture, and drought over southeast Australia were also investigated. Results indicate that vegetation fraction changes lag precipitation reductions by 6–8 months in nonarid regions. With the onset of the 2002 drought, a potential fast physical mechanism was found to play a positive role in the soil moisture–precipitation feedback, while a slow biological mechanism provides a negative feedback in the soil moisture–precipitation interaction on a longer time scale. That is, in the short term, a reduction in soil moisture leads to a reduction in the convective potential and, hence, precipitation, further reducing the soil moisture. If low levels of soil moisture persist long enough, reductions in vegetation cover and vigor occur, reducing the evapotranspiration and thus reducing the soil moisture decreases and dampening the fast physical feedback. Importantly, it was observed that these feedbacks are both space and time dependent.

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

International Nuclear Information System (INIS)

Liu, Zi-Miao; Tseng, Hong-Yu; Cheng, Ya-Ling; Yeh, Bi-Wen; Wu, Wen-Jeng; Huang, Huei-Sheng

2015-01-01

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-dependent kinase inhibitor CDKN1A (p21 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

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

Energy Technology Data Exchange (ETDEWEB)

Liu, Zi-Miao; Tseng, Hong-Yu; Cheng, Ya-Ling [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Yeh, Bi-Wen [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Wu, Wen-Jeng [Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Huang, Huei-Sheng, E-mail: huanghs@mail.ncku.edu.tw [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China)

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-dependent 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

Integrated regional changes in arctic climate feedbacks: Implications for the global climate system

Science.gov (United States)

McGuire, A.D.; Chapin, F. S.; Walsh, J.E.; Wirth, C.; ,

2006-01-01

The Arctic is a key part of the global climate system because the net positive energy input to the tropics must ultimately be resolved through substantial energy losses in high-latitude regions. The Arctic influences the global climate system through both positive and negative feedbacks that involve physical, ecological, and human systems of the Arctic. The balance of evidence suggests that positive feedbacks to global warming will likely dominate in the Arctic during the next 50 to 100 years. However, the negative feedbacks associated with changing the freshwater balance of the Arctic Ocean might abruptly launch the planet into another glacial period on longer timescales. In light of uncertainties and the vulnerabilities of the climate system to responses in the Arctic, it is important that we improve our understanding of how integrated regional changes in the Arctic will likely influence the evolution of the global climate system. Copyright ?? 2006 by Annual Reviews. All rights reserved.

Relaxation rates of gene expression kinetics reveal the feedback signs of autoregulatory gene networks

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Jia, Chen; Qian, Hong; Chen, Min; Zhang, Michael Q.

2018-03-01

The transient response to a stimulus and subsequent recovery to a steady state are the fundamental characteristics of a living organism. Here we study the relaxation kinetics of autoregulatory gene networks based on the chemical master equation model of single-cell stochastic gene expression with nonlinear feedback regulation. We report a novel relation between the rate of relaxation, characterized by the spectral gap of the Markov model, and the feedback sign of the underlying gene circuit. When a network has no feedback, the relaxation rate is exactly the decaying rate of the protein. We further show that positive feedback always slows down the relaxation kinetics while negative feedback always speeds it up. Numerical simulations demonstrate that this relation provides a possible method to infer the feedback topology of autoregulatory gene networks by using time-series data of gene expression.

About Politeness, Face, and Feedback: Exploring Resident and Faculty Perceptions of How Institutional Feedback Culture Influences Feedback Practices.

Science.gov (United States)

Ramani, Subha; Könings, Karen D; Mann, Karen V; Pisarski, Emily E; van der Vleuten, Cees P M

2018-03-06

To explore resident and faculty perspectives on what constitutes feedback culture, their perceptions of how institutional feedback culture (including politeness concepts) might influence the quality and impact of feedback, feedback seeking, receptivity, and readiness to engage in bidirectional feedback. Using a constructivist grounded theory approach, five focus group discussions with internal medicine residents, three focus group discussions with general medicine faculty, and eight individual interviews with subspecialist faculty were conducted at Brigham and Women's Hospital between April and December 2016. Discussions and interviews were audiotaped and transcribed verbatim; concurrent data collection and analysis were performed using the constant comparative approach. Analysis was considered through the lens of politeness theory and organizational culture. Twenty-nine residents and twenty-two general medicine faculty participated in focus group discussions, and eight subspecialty faculty participated in interviews. The institutional feedback culture was described by participants as: (1) a culture of politeness, in which language potentially damaging to residents' self-esteem was discouraged, and (2) a culture of excellence, in which the institution's outstanding reputation and pedigree of trainees inhibited constructive feedback. Three key themes situated within this broader cultural context were discovered: normalizing constructive feedback to promote a culture of growth, overcoming the mental block to feedback seeking, and hierarchical culture impeding bidirectional feedback. An institutional feedback culture of excellence and politeness may impede honest, meaningful feedback and may impact feedback seeking, receptivity, and bidirectional feedback exchanges. It is essential to understand the institutional feedback culture before it can be successfully changed.

Youth fitness testing: the effect of percentile-based evaluative feedback on intrinsic motivation.

Science.gov (United States)

Whitehead, J R; Corbin, C B

1991-06-01

This study was a test of Deci and Ryan's (1985) cognitive evaluation theory in a fitness testing situation. More specifically, it was a test of Proposition 2 of that theory, which posits that external events that increase or decrease perceived competence will increase or decrease intrinsic motivation. Seventh and eighth grade schoolchildren (N = 105) volunteered for an experiment that was ostensibly to collect data on a new youth fitness test (the Illinois Agility Run). After two untimed practice runs, a specially adapted version of the Intrinsic Motivation Inventory (IMI) was administered as a pretest of intrinsic motivation. Two weeks later when subjects ran again, they were apparently electronically timed. In reality, the subjects were given bogus feedback. Subjects in a positive feedback condition were told their scores were above the 80th percentile, while those in a negative feedback condition were told their scores were below the 20th percentile. Those in a control condition received no feedback. The IMI was again administered to the subjects after their runs. Multivariate and subsequent univariate tests were significant for all four subscale dependent variables (perceived interest-enjoyment, competence, effort, and pressure-tension). Positive feedback enhanced all aspects of intrinsic motivation, whereas negative feedback decreased them. In a further test of cognitive evaluation theory, path analysis results supported the prediction that perceived competence would mediate changes in the other IMI subscales. Taken together, these results clearly support cognitive evaluation theory and also may have important implications regarding motivation for those who administer youth fitness tests.

Dynamics of gene expression with positive feedback to histone modifications at bivalent domains

Science.gov (United States)

Huang, Rongsheng; Lei, Jinzhi

2018-03-01

Experiments have shown that in embryonic stem cells, the promoters of many lineage-control genes contain “bivalent domains”, within which the nucleosomes possess both active (H3K4me3) and repressive (H3K27me3) marks. Such bivalent modifications play important roles in maintaining pluripotency in embryonic stem cells. Here, to investigate gene expression dynamics when there are regulations in bivalent histone modifications and random partition in cell divisions, we study how positive feedback to histone methylation/demethylation controls the transition dynamics of the histone modification patterns along with cell cycles. We constructed a computational model that includes dynamics of histone marks, three-stage chromatin state transitions, transcription and translation, feedbacks from protein product to enzymes to regulate the addition and removal of histone marks, and the inheritance of nucleosome state between cell cycles. The model reveals how dynamics of both nucleosome state transition and gene expression are dependent on the enzyme activities and feedback regulations. Results show that the combination of stochastic histone modification at each cell division and the deterministic feedback regulation work together to adjust the dynamics of chromatin state transition in stem cell regenerations.

Transcript-specific effects of adrenalectomy on seizure-induced BDNF expression in rat hippocampus

DEFF Research Database (Denmark)

Lauterborn, J C; Poulsen, F R; Stinis, C T

1998-01-01

Activity-induced brain-derived neurotrophic factor (BDNF) expression is negatively modulated by circulating adrenal steroids. The rat BDNF gene gives rise to four major transcript forms that each contain a unique 5' exon (I-IV) and a common 3' exon (V) that codes for BDNF protein. Exon-specific i......Activity-induced brain-derived neurotrophic factor (BDNF) expression is negatively modulated by circulating adrenal steroids. The rat BDNF gene gives rise to four major transcript forms that each contain a unique 5' exon (I-IV) and a common 3' exon (V) that codes for BDNF protein. Exon...... and in exon II-containing mRNA with 30-days survival. In the dentate gyrus granule cells, adrenalectomy markedly potentiated increases in exon I and II cRNA labeling, but not increases in exon III and IV cRNA labeling, elicited by one hippocampal afterdischarge. Similarly, for the granule cells and CA1...... no effect on exon IV-containing mRNA content. These results demonstrate that the negative effects of adrenal hormones on activity-induced BDNF expression are by far the greatest for transcripts containing exons I and II. Together with evidence for region-specific transcript expression, these results suggest...

Effects of cytosine methylation on transcription factor binding sites

KAUST Repository

Medvedeva, Yulia A

2014-03-26

Background: DNA methylation in promoters is closely linked to downstream gene repression. However, whether DNA methylation is a cause or a consequence of gene repression remains an open question. If it is a cause, then DNA methylation may affect the affinity of transcription factors (TFs) for their binding sites (TFBSs). If it is a consequence, then gene repression caused by chromatin modification may be stabilized by DNA methylation. Until now, these two possibilities have been supported only by non-systematic evidence and they have not been tested on a wide range of TFs. An average promoter methylation is usually used in studies, whereas recent results suggested that methylation of individual cytosines can also be important.Results: We found that the methylation profiles of 16.6% of cytosines and the expression profiles of neighboring transcriptional start sites (TSSs) were significantly negatively correlated. We called the CpGs corresponding to such cytosines " traffic lights" We observed a strong selection against CpG " traffic lights" within TFBSs. The negative selection was stronger for transcriptional repressors as compared with transcriptional activators or multifunctional TFs as well as for core TFBS positions as compared with flanking TFBS positions.Conclusions: Our results indicate that direct and selective methylation of certain TFBS that prevents TF binding is restricted to special cases and cannot be considered as a general regulatory mechanism of transcription. 2013 Medvedeva et al.; licensee BioMed Central Ltd.

Assessment of Habitat Suitability Is Affected by Plant-Soil Feedback: Comparison of Field and Garden Experiment.

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Lucie Hemrová

Full Text Available Field translocation experiments (i.e., the introduction of seeds or seedlings of different species into different localities are commonly used to study habitat associations of species, as well as factors limiting species distributions and local abundances. Species planted or sown in sites where they naturally occur are expected to perform better or equally well compared to sites at which they do not occur or are rare. This, however, contrasts with the predictions of the Janzen-Connell hypothesis and commonly reported intraspecific negative plant-soil feedback. The few previous studies indicating poorer performance of plants at sites where they naturally occur did not explore the mechanisms behind this pattern.In this study, we used field translocation experiments established using both seeds and seedlings to study the determinants of local abundance of four dominant species in grasslands. To explore the possible effects of intraspecific negative plant-soil feedback on our results, we tested the effect of local species abundance on the performance of the plants in the field experiment. In addition, we set up a garden experiment to explore the intensity of intraspecific as well as interspecific feedback between the dominants used in the experiment.In some cases, the distribution and local abundances of the species were partly driven by habitat conditions at the sites, and species performed better at their own sites. However, the prevailing pattern was that the local dominants performed worse at sites where they naturally occur than at any other sites. Moreover, the success of plants in the field experiment was lower in the case of higher intraspecific abundance prior to experimental setup. In the garden feedback experiment, two of the species performed significantly worse in soils conditioned by their species than in soils conditioned by the other species. In addition, the performance of the plants was significantly correlated between the two

All about the money – External performance monitoring is affected by monetary, but not by socially conveyed feedback cues in more antisocial individuals

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Daniela Melitta Pfabigan

2011-09-01

Full Text Available This study investigated the relationship between feedback processing and antisocial personality traits measured by the PSSI questionnaire (Kuhl & Kazén, 1997 in a healthy undergraduate sample. While event-related potentials (Feedback Related Negativity [FRN], P300 were recorded, participants encountered expected and unexpected feedback during a gambling task. As recent findings suggest learning problems and deficiencies during feedback processing in clinical populations of antisocial individuals, we performed two experiments with different healthy participants in which feedback about monetary gains or losses consisted either of social-emotional (facial emotion displays or non-social cues (numerical stimuli. Since the FRN and P300 are both sensitive to different aspects of feedback processing we hypothesized that they might help to differentiate between individuals scoring high and low on an antisocial trait measure.In line with previous evidence FRN amplitudes were enhanced after negative and after unexpected feedback stimuli. Crucially, participants scoring high on antisocial traits displayed larger FRN amplitudes than those scoring low only in response to expected and unexpected negative numerical feedback, but not in response to social-emotional feedback - irrespective of expectancy. P300 amplitudes were not modulated by antisocial traits at all, but by subjective reward probabilities. The present findings indicate that individuals scoring high on antisociality attribute higher motivational salience to monetary compared to emotional-social feedback which is reflected in FRN amplitude enhancement. Contrary to recent findings, however, no processing deficiencies concerning social-emotional feedback stimuli were apparent in those individuals. This indicates that stimulus salience is an important aspect in learning and feedback processes in individuals with antisocial traits which has potential implications for therapeutic interventions in

Combined Audience and Video Feedback With Cognitive Review Improves State Anxiety and Self-Perceptions During Speech Tasks in Socially Anxious Individuals.

Science.gov (United States)

Chen, Junwen; McLean, Jordan E; Kemps, Eva

2018-03-01

This study investigated the effects of combined audience feedback with video feedback plus cognitive preparation, and cognitive review (enabling deeper processing of feedback) on state anxiety and self-perceptions including perception of performance and perceived probability of negative evaluation in socially anxious individuals during a speech performance. One hundred and forty socially anxious students were randomly assigned to four conditions: Cognitive Preparation + Video Feedback + Audience Feedback + Cognitive Review (CP+VF+AF+CR), Cognitive Preparation + Video Feedback + Cognitive Review (CP+VF+CR), Cognitive Preparation + Video Feedback only (CP+VF), and Control. They were asked to deliver two impromptu speeches that were evaluated by confederates. Participants' levels of anxiety and self-perceptions pertaining to the speech task were assessed before and after feedback, and after the second speech. Compared to participants in the other conditions, participants in the CP+VF+AF+CR condition reported a significant decrease in their state anxiety and perceived probability of negative evaluation scores, and a significant increase in their positive perception of speech performance from before to after the feedback. These effects generalized to the second speech. Our results suggest that adding audience feedback to video feedback plus cognitive preparation and cognitive review may improve the effects of existing video feedback procedures in reducing anxiety symptoms and distorted self-representations in socially anxious individuals. Copyright © 2017. Published by Elsevier Ltd.

A Model Of Critical Peer Feedback To Facilitate Business English Writing Using Qzone Weblogs Among Chinese Undergraduates

Directory of Open Access Journals (Sweden)

Gao Xianwei

2016-10-01

Full Text Available The purpose of this study was to explore critical thinking skills in peer feedback for Business English writing in order to facilitate the quality of peer feedback and quality of Business English writing. “Critical peer feedback” was conceptualized with the integration of “critical thinking” and “peer feedback” in order to improve the quality of peer feedback. This study explored the process, content and factors of critical peer feedback through Qzone weblogs, and summarized the model of critical peer feedback. A qualitative case study was conducted with a group of six junior students majoring in Business English for one semester in a Chinese university. Three models of critical thinking including Revised Bloom’s Taxonomy, Paul-Elder Model and Reichenbach’s Six Steps Model, were transferred to the participants in the workshops. Three kinds of data including semi-structured interview transcripts, six writing assignments and artifacts of critical peer feedback, were analyzed by QSR NVivo 8. The findings revealed that the Revised Bloom’s Taxonomy is more acceptable for the beginners of critical peer feedback which provides a six-step model of critical thinking. The process of critical peer feedback in online context was summarized as four steps- “intake”, “critical thinking”, “output”, and “post-output”. Each of the four steps had several mental processes in critical peer feedback. This study may be significant for the knowledge of higher-order peer feedback to facilitate the quality of higher-level writing.

Hybrid modeling of the crosstalk between signaling and transcriptional networks using ordinary differential equations and multi-valued logic.

Science.gov (United States)

Khan, Faiz M; Schmitz, Ulf; Nikolov, Svetoslav; Engelmann, David; Pützer, Brigitte M; Wolkenhauer, Olaf; Vera, Julio

2014-01-01

A decade of successful results indicates that systems biology is the appropriate approach to investigate the regulation of complex biochemical networks involving transcriptional and post-transcriptional regulations. It becomes mandatory when dealing with highly interconnected biochemical networks, composed of hundreds of compounds, or when networks are enriched in non-linear motifs like feedback and feedforward loops. An emerging dilemma is to conciliate models of massive networks and the adequate description of non-linear dynamics in a suitable modeling framework. Boolean networks are an ideal representation of massive networks that are humble in terms of computational complexity and data demand. However, they are inappropriate when dealing with nested feedback/feedforward loops, structural motifs common in biochemical networks. On the other hand, models of ordinary differential equations (ODEs) cope well with these loops, but they require enormous amounts of quantitative data for a full characterization of the model. Here we propose hybrid models, composed of ODE and logical sub-modules, as a strategy to handle large scale, non-linear biochemical networks that include transcriptional and post-transcriptional regulations. We illustrate the construction of this kind of models using as example a regulatory network centered on E2F1, a transcription factor involved in cancer. The hybrid modeling approach proposed is a good compromise between quantitative/qualitative accuracy and scalability when considering large biochemical networks with a small highly interconnected core, and module of transcriptionally regulated genes that are not part of critical regulatory loops. This article is part of a Special Issue entitled: Computational Proteomics, Systems Biology & Clinical Implications. Guest Editor: Yudong Cai. Copyright © 2013 Elsevier B.V. All rights reserved.

Ventral tegmental area orexin 1 receptors promote palatable food intake and oppose postingestive negative feedback.

Science.gov (United States)

Terrill, Sarah J; Hyde, Kellie M; Kay, Kristen E; Greene, Hayden E; Maske, Calyn B; Knierim, Amanda E; Davis, Jon F; Williams, Diana L

2016-09-01

Hypothalamic orexin neurons project to numerous brain areas, including the ventral tegmental area (VTA), which is involved in motivation and food-seeking behavior. Here we address how exogenously administered orexin-A and endogenous orexin 1 receptor (OX1R) activation in the VTA affects feeding behavior. We hypothesized that orexin-A and OX1R antagonist SB334867 delivered to the VTA, at doses that were subthreshold for effect when injected into the ventricle, would affect intake of palatable foods in multiple test situations. We first used a hedonic feeding model in which satiated rats selectively consume a high-fat diet (HFD). Intra-VTA orexin-A stimulated additional consumption of chow and increased HFD intake in this model. In ad libitum-fed rats given daily 30-min test sessions, intra-VTA orexin-A also increased intake of HFD and 0.1 M sucrose. Further analysis of licking patterns revealed that that VTA orexin-A increased meal size and licking burst size only toward the end of the meal. Consistent with this finding, a subthreshold dose of VTA orexin-A prevented intake suppression induced by gastrointestinal nutrient infusion. Surprisingly, intra-VTA orexin-A had no effect on operant responding for sucrose pellets on a progressive ratio schedule of reinforcement. A role for endogenous VTA OX1R stimulation is supported by our finding that bilateral VTA injection of the selective OX1R antagonist SB334867 suppressed 0.1 M sucrose intake. Together, our data suggest that OX1R activity in the VTA facilitates food intake, potentially by counteracting postingestive negative feedback that would normally suppress feeding later in a meal. Copyright © 2016 the American Physiological Society.

Dynamical consequences of bandpass feedback loops in a bacterial phosphorelay.

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Shaunak Sen

Full Text Available Under conditions of nutrient limitation, Bacillus subtilis cells terminally differentiate into a dormant spore state. Progression to sporulation is controlled by a genetic circuit consisting of a phosphorelay embedded in multiple transcriptional feedback loops, which is used to activate the master regulator Spo0A by phosphorylation. These transcriptional regulatory interactions are "bandpass"-like, in the sense that activation occurs within a limited band of Spo0A∼P concentrations. Additionally, recent results show that the phosphorelay activation occurs in pulses, in a cell-cycle dependent fashion. However, the impact of these pulsed bandpass interactions on the circuit dynamics preceding sporulation remains unclear. In order to address this question, we measured key features of the bandpass interactions at the single-cell level and analyzed them in the context of a simple mathematical model. The model predicted the emergence of a delayed phase shift between the pulsing activity of the different sporulation genes, as well as the existence of a stable state, with elevated Spo0A activity but no sporulation, embedded within the dynamical structure of the system. To test the model, we used time-lapse fluorescence microscopy to measure dynamics of single cells initiating sporulation. We observed the delayed phase shift emerging during the progression to sporulation, while a re-engineering of the sporulation circuit revealed behavior resembling the predicted additional state. These results show that periodically-driven bandpass feedback loops can give rise to complex dynamics in the progression towards sporulation.

Replicative Stress Induces Intragenic Transcription of the ASE1 Gene that Negatively Regulates Ase1 Activity

OpenAIRE

McKnight, Kelly; Liu, Hong; Wang, Yanchang

2014-01-01

Intragenic transcripts initiate within the coding region of a gene, thereby producing shorter mRNAs and proteins. Although intragenic transcripts are widely expressed [1], their role in the functional regulation of genes remains largely unknown. In budding yeast, DNA replication stress activates the S-phase checkpoint that stabilizes replication forks and arrests cells in S-phase with a short spindle [2-4]. When yeast cells were treated with hydroxyurea (HU) to block DNA synthesis and induce ...

TRIM30α Is a Negative-Feedback Regulator of the Intracellular DNA and DNA Virus-Triggered Response by Targeting STING.

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Yanming Wang

2015-06-01

Full Text Available Uncontrolled immune responses to intracellular DNA have been shown to induce autoimmune diseases. Homeostasis regulation of immune responses to cytosolic DNA is critical for limiting the risk of autoimmunity and survival of the host. Here, we report that the E3 ubiquitin ligase tripartite motif protein 30α (TRIM30α was induced by herpes simplex virus type 1 (HSV-1 infection in dendritic cells (DCs. Knockdown or genetic ablation of TRIM30α augmented the type I IFNs and interleukin-6 response to intracellular DNA and DNA viruses. Trim30α-deficient mice were more resistant to infection by DNA viruses. Biochemical analyses showed that TRIM30α interacted with the stimulator of interferon genes (STING, which is a critical regulator of the DNA-sensing response. Overexpression of TRIM30α promoted the degradation of STING via K48-linked ubiquitination at Lys275 through a proteasome-dependent pathway. These findings indicate that E3 ligase TRIM30α is an important negative-feedback regulator of innate immune responses to DNA viruses by targeting STING.

Affective-motivational influences on feedback-related ERPs in a gambling task.

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Masaki, Hiroaki; Takeuchi, Shigeki; Gehring, William J; Takasawa, Noriyoshi; Yamazaki, Katuo

2006-08-11

Theories have proposed that both the stimulus-preceding negativity (SPN) and the medial frontal negativity (MFN) reflect affective/motivational processing. We examined the effect of the motivational impact of feedback stimuli on these ERPs using a simple gambling task, focusing on the influence of prior losses and gains on ERPs and choice behavior. Choices were riskier following large losses than following small losses or large gains. The MFN, however, was larger following larger gains. The SPN preceding the outcome was also larger after a greater gain. Thus, we confirmed that both the MFN and the SPN respond to the motivational properties of the feedback. A dissociation between risk-taking behavior and these ERPs suggests that there could be two monitoring systems: one that leads to riskier responses following losses and a second that leads to heightened expectancy.

Sensory Processing: Advances in Understanding Structure and Function of Pitch-Shifted Auditory Feedback in Voice Control

OpenAIRE

Charles R Larson; Donald A Robin

2016-01-01

The pitch-shift paradigm has become a widely used method for studying the role of voice pitch auditory feedback in voice control. This paradigm introduces small, brief pitch shifts in voice auditory feedback to vocalizing subjects. The perturbations trigger a reflexive mechanism that counteracts the change in pitch. The underlying mechanisms of the vocal responses are thought to reflect a negative feedback control system that is similar to constructs developed to explain other forms of motor ...

Processing of ambiguous and unambiguous feedback by depressed and nondepressed college students: schematic biases and their implications for depressive realism.

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Dykman, B M; Abramson, L Y; Alloy, L B; Hartlage, S

1989-03-01

Explored schematic processing as a mechanism for predicting (a) when depressed Ss would be negative relative to nondepressed Ss and (b) when depressed and nondepressed Ss would show biased or unbiased (i.e., "realistic") processing. Depressed and nondepressed Ss performed multiple trials of a task under conditions in which the two groups held either equivalent or different schemas regarding this task. Ss received either an unambiguous or objectively normed ambiguous feedback cue on each trial. In full support of schematic processing, depressed Ss showed negative encoding relative to nondepressed Ss only when their schemas were more negative, and both depressed and nondepressed Ss showed positively biased, negatively biased, and unbiased encoding depending on the relative feedback cue-to-schema match. Depressed and nondepressed Ss' response latencies to unambiguous feedback also supported the occurrence of schematic processing. We discuss the methodological, treatment, and "realism" implications of these findings and suggest a more precise formulation of Beck's schema theory of depression.

Effects of continuous feedback on households’ electricity consumption: Potentials and barriers

International Nuclear Information System (INIS)

Nilsson, Andreas; Bergstad, Cecilia Jakobsson; Thuvander, Liane; Andersson, David; Andersson, Kristin; Meiling, Pär

2014-01-01

Highlights: • Two studies on conservation behaviours using in home-displays are presented. • No significant effects on electricity consumption were found. • Display feedback does not necessarily contribute to lower electricity use. • Interviews conclude that different types of feedback techniques should be combined. • Two important barriers are difficulties to understand the display and a lack of interest. - Abstract: Two field experiments were carried out to study (a) the effects on energy savings of continuous visual feedback via in-home displays, and (b) the motives for responding or not. In study 1, 40 participants living in separate or semi-detached houses in two different towns participated. All participants received a questionnaire and a list of possible energy saving measures. Households were then randomly assigned to an experimental condition (display) or a control condition (no display). In study 2, 32 households in rented apartments participated. No significant differences between the conditions were found for either of the studies. In study 2, semi-structured interviews were conducted among nine of the households. Through an analysis of interview transcripts barriers were identified explaining why the feedback intervention was not sufficient to change behaviour and reduce consumption. The barriers experienced indicate that there is a risk of overconfidence in IHDs. For the development of energy policies and more wide-scale implementation, it is important to be aware of the potential obstacles to success

The Impact of Feedback on the Different Time Courses of Multisensory Temporal Recalibration

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Matthew A. De Niear

2017-01-01

Full Text Available The capacity to rapidly adjust perceptual representations confers a fundamental advantage when confronted with a constantly changing world. Unexplored is how feedback regarding sensory judgments (top-down factors interacts with sensory statistics (bottom-up factors to drive long- and short-term recalibration of multisensory perceptual representations. Here, we examined the time course of both cumulative and rapid temporal perceptual recalibration for individuals completing an audiovisual simultaneity judgment task in which they were provided with varying degrees of feedback. We find that in the presence of feedback (as opposed to simple sensory exposure temporal recalibration is more robust. Additionally, differential time courses are seen for cumulative and rapid recalibration dependent upon the nature of the feedback provided. Whereas cumulative recalibration effects relied more heavily on feedback that informs (i.e., negative feedback rather than confirms (i.e., positive feedback the judgment, rapid recalibration shows the opposite tendency. Furthermore, differential effects on rapid and cumulative recalibration were seen when the reliability of feedback was altered. Collectively, our findings illustrate that feedback signals promote and sustain audiovisual recalibration over the course of cumulative learning and enhance rapid trial-to-trial learning. Furthermore, given the differential effects seen for cumulative and rapid recalibration, these processes may function via distinct mechanisms.

O-GlcNAc inhibits interaction between Sp1 and Elf-1 transcription factors

International Nuclear Information System (INIS)

Lim, Kihong; Chang, Hyo-Ihl

2009-01-01

The novel protein modification, O-linked N-acetylglucosamine (O-GlcNAc), plays an important role in various aspects of cell regulation. Although most of nuclear transcription regulatory factors are modified by O-GlcNAc, O-GlcNAc effects on transcription remain largely undefined yet. In this study, we show that O-GlcNAc inhibits a physical interaction between Sp1 and Elf-1 transcription factors, and negatively regulates transcription of placenta and embryonic expression oncofetal protein gene (Pem). These findings suggest that O-GlcNAc inhibits Sp1-mediated gene transcription possibly by interrupting Sp1 interaction with its cooperative factor.

Observational Signatures Of Agn Feedback Across Cosmic Time