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Sample records for affect regulation model

  1. Interactions of Metacognition with Motivation and Affect in Self-Regulated Learning: The MASRL Model

    ERIC Educational Resources Information Center

    Efklides, Anastasia

    2011-01-01

    Metacognition, motivation, and affect are components of self-regulated learning (SRL) that interact. The "metacognitive and affective model of self-regulated learning" (the MASRL model) distinguishes two levels of functioning in SRL, namely, the Person level and the Task x Person level. At the Person level interactions between trait-like…

  2. Integrating Negative Affect Measures in a Measurement Model: Assessing the Function of Negative Affect as Interference to Self-Regulation

    ERIC Educational Resources Information Center

    Magno, Carlo

    2010-01-01

    The present study investigated the composition of negative affect and its function as inhibitory to thought processes such as self-regulation. Negative affect in the present study were composed of anxiety, worry, thought suppression, and fear of negative evaluation. These four factors were selected based on the criteria of negative affect by…

  3. Revisiting the Affect Regulation Model of Binge Eating: A Meta-Analysis of Studies Using Ecological Momentary Assessment

    ERIC Educational Resources Information Center

    Haedt-Matt, Alissa A.; Keel, Pamela K.

    2011-01-01

    The affect regulation model of binge eating, which posits that patients binge eat to reduce negative affect (NA), has received support from cross-sectional and laboratory-based studies. Ecological momentary assessment (EMA) involves momentary ratings and repeated assessments over time and is ideally suited to identify temporal antecedents and…

  4. An integrative affect regulation process model of internalized weight bias and intuitive eating in college women.

    PubMed

    Webb, Jennifer B; Hardin, Abigail S

    2016-07-01

    The present study extended the weight stigma and well-being process model (Tylka et al., 2014) by examining three affect regulation pathways that may help simultaneously explain the predicted inverse association between internalized weight bias and intuitive eating. A weight-diverse sample of 333 college women completed an online survey assessing internalized weight stigma, intuitive eating, body shame, body image flexibility, and self-compassion. Self-reported height and weight were used to calculate body mass index (BMI). Non-parametric bootstrap resampling procedures were computed to ascertain the presence of the indirect effects of internalized weight bias on intuitive eating via the three hypothesized mediators controlling for BMI in a combined model. Results demonstrated that body image flexibility significantly and self-compassion marginally contributed unique variance in accounting for this relationship. Our preliminary cross-sectional findings contribute to a nascent body of scholarship seeking to provide a theoretically-driven understanding of how negative and positive forms of experiencing and relating to the body may co-occur within individuals. Results also point to potential target variables to consider incorporating in later-stage efforts to promote more adaptive ways of eating amidst internalized weight stigma. PMID:26893074

  5. Affect and Self-Regulation

    ERIC Educational Resources Information Center

    Malmivuori, Marja-Liisa

    2006-01-01

    This paper presents affect as an essential aspect of students' self-reflection and self-regulation. The introduced concepts of self-system and self-system process stress the importance of self-appraisals of personal competence and agency in affective responses and self-regulation in problem solving. Students are viewed as agents who constantly…

  6. Loving-kindness in the treatment of traumatized refugees and minority groups: a typology of mindfulness and the nodal network model of affect and affect regulation.

    PubMed

    Hinton, Devon E; Ojserkis, Rebecca A; Jalal, Baland; Peou, Sonith; Hofmann, Stefan G

    2013-08-01

    This article discusses how loving-kindness can be used to treat traumatized refugees and minority groups, focusing on examples from our treatment, culturally adapted cognitive-behavioral therapy (CA-CBT). To show how we integrate loving-kindness with other mindfulness interventions and why loving-kindness should be an effective therapeutic technique, we present a typology of mindfulness states and the Nodal Network Model (NNM) of Affect and Affect Regulation. We argue that mindfulness techniques such as loving-kindness are therapeutic for refugees and minority populations because of their potential for increasing emotional flexibility, decreasing rumination, serving as emotional regulation techniques, and forming part of a new adaptive processing mode centered on psychological flexibility. We present a case to illustrate the clinical use of loving-kindness within the context of CA-CBT. PMID:23784718

  7. The Affective Regulation of Cognitive Priming

    PubMed Central

    Storbeck, Justin; Clore, Gerald L.

    2008-01-01

    Semantic and affective priming are classic effects observed in cognitive and social psychology, respectively. We discovered that affect regulates such priming effects. In Experiment 1, positive and negative moods were induced prior to one of three priming tasks; evaluation, categorization, or lexical decision. As predicted, positive affect led to both affective priming (evaluation task) and semantic priming (category and lexical decision tasks). However, negative affect inhibited such effects. In Experiment 2, participants in their natural affective state completed the same priming tasks as in Experiment 1. As expected, affective priming (evaluation task) and category priming (categorization and lexical decision tasks) were observed in such resting affective states. Hence, we conclude that negative affect inhibits semantic and affective priming. These results support recent theoretical models, which suggest that positive affect promotes associations among strong and weak concepts, and that negative affect impairs such associations (Kuhl, 2000; Clore & Storbeck, 2006). PMID:18410195

  8. Musical affect regulation in infancy.

    PubMed

    Trehub, Sandra E; Ghazban, Niusha; Corbeil, Mariève

    2015-03-01

    Adolescents and adults commonly use music for various forms of affect regulation, including relaxation, revitalization, distraction, and elicitation of pleasant memories. Mothers throughout the world also sing to their infants, with affect regulation as the principal goal. To date, the study of maternal singing has focused largely on its acoustic features and its consequences for infant attention. We describe recent laboratory research that explores the consequences of singing for infant affect regulation. Such work reveals that listening to recordings of play songs can maintain 6- to 9-month-old infants in a relatively contented or neutral state considerably longer than recordings of infant-directed or adult-directed speech. When 10-month-old infants fuss or cry and are highly aroused, mothers' multimodal singing is more effective than maternal speech at inducing recovery from such distress. Moreover, play songs are more effective than lullabies at reducing arousal in Western infants. We explore the implications of these findings along with possible practical applications. PMID:25773634

  9. Understanding regulations affecting pet foods.

    PubMed

    Dzanis, David A

    2008-08-01

    In the United States, pet foods are subject to regulation at both the federal and the state levels. The US Food and Drug Administration has jurisdiction over all animal feeds (including pet foods, treats, chews, supplements, and ingredients) in interstate commerce, which includes imported products. Many states adopt and enforce at least in part the Association of American Feed Control Officials Model Bill and Model Regulations for Pet Food and Specialty Pet Food. Thus, all pet foods in multi-state distribution are subject to a host of labeling requirements covering aspects such as product names, ingredient lists, nutrient content guarantees, and nutritional adequacy statements. Ingredients must be GRAS (generally recognized as safe) substances, approved food additives, or defined by Association of American Feed Control Officials for their intended use. Pet food labels may not bear claims that are false or misleading or that state or imply use for the treatment or prevention of disease. Pet foods that are found to be adulterated or misbranded may be subject to seizure or other enforcement actions. PMID:18656837

  10. Do Emotional Eating Urges Regulate Affect? Concurrent and Prospective Associations and Implications for Risk Models of Binge Eating

    PubMed Central

    Haedt-Matt, Alissa A.; Keel, Pamela K.; Racine, Sarah E.; Burt, S. Alexandra; Hu, Jean Yueqin; Boker, Steven; Neale, Michael; Klump, Kelly L.

    2014-01-01

    Objective Emotional eating (EE) reflects an urge to eat in response to emotional rather than physical cues and is a risk factor for the development of binge eating. EE has been conceptualized as an attempt to regulate negative affect (NA), a posited maintenance factor for binge eating. However, no study has examined whether EE urges regulate affect. Further, no studies have examined longitudinal associations between EE urges and positive affect (PA). Method We examined within-subject longitudinal associations between affect and EE urges in a community-based sample of female twins (mean age=17.8 years). Participants (N=239) completed ratings of affect and EE urges for 45 consecutive days. Results Greater NA was concurrently associated with greater EE urges. Additionally, greater EE urges predicted worse NA for both concurrent and prospective (next-day) analyses. Finally, lower PA was associated with greater EE urges in concurrent analyses, but there were no prospective associations between changes in PA and EE urges. Discussion EE urges do not appear to effectively regulate affect. EE urges in a community-based sample appears to have the same functional relationship with affect as binge eating in clinical samples, further supporting EE as a useful dimensional construct for examining processes related to binge eating. PMID:24431328

  11. Affect regulation: holding, containing and mirroring.

    PubMed

    Pedersen, Signe Holm; Poulsen, Stig; Lunn, Susanne

    2014-10-01

    Gergely and colleagues' state that their "Social Biofeedback Theory of Parental Affect Mirroring" can be seen as a kind of operationalization of the classical psychoanalytic concepts of holding, containing and mirroring. This article examines to what extent the social biofeedback theory of parental affect mirroring may be understood as a specification of these concepts. It is argued that despite similarities at a descriptive level the concepts are embedded in theories with different ideas of subjectivity. Hence an understanding of the concept of affect regulation as a concretization and specification of the classical concepts dilutes the complexity of both the concept of affect regulation and of the classical concepts. PMID:25351730

  12. The affective shift model of work engagement.

    PubMed

    Bledow, Ronald; Schmitt, Antje; Frese, Michael; Kühnel, Jana

    2011-11-01

    On the basis of self-regulation theories, the authors develop an affective shift model of work engagement according to which work engagement emerges from the dynamic interplay of positive and negative affect. The affective shift model posits that negative affect is positively related to work engagement if negative affect is followed by positive affect. The authors applied experience sampling methodology to test the model. Data on affective events, mood, and work engagement was collected twice a day over 9 working days among 55 software developers. In support of the affective shift model, negative mood and negative events experienced in the morning of a working day were positively related to work engagement in the afternoon if positive mood in the time interval between morning and afternoon was high. Individual differences in positive affectivity moderated within-person relationships. The authors discuss how work engagement can be fostered through affect regulation. PMID:21766997

  13. Exporting licensing regulations affecting US geothermal firms

    SciTech Connect

    Not Available

    1988-08-01

    This document presents a brief introduction and overview of the Department of Commerce's Export Administration Regulations which might affect potential US geothermal goods exporters. It is intended to make US geothermal firms officials aware of the existence of such regulations and to provide them with references, contacts and phone numbers where they can obtain specific and detailed information and assistance. It must be stressed however, that the ultimate responsibility for complying with the above mentioned regulations lies with the exporter who must consult the complete version of the regulations.

  14. The Affective Regulation of Social Interaction*

    PubMed Central

    Clore, Gerald L.; Pappas, Jesse

    2008-01-01

    The recent publication of David Heise’s Expressive Order (2007) provides an occasion for discussing some of the key ideas in Affect Control Theory. The theory proposes that a few dimensions of affective meaning provide a common basis for interrelating personal identities and social actions. It holds that during interpersonal interactions, social behavior is continually regulated to maintain an affective tone compatible with whatever social roles or identities define the situation. We outline the intellectual history of the proposed dimensions and of the idea that each social action invites an action from the other that has a particular location along these dimensions. We also relate these ideas to the Affect-as-Information hypothesis, an approach that often guides research in psychology on the role of affect in regulating judgment and thought. PMID:18461152

  15. ONO-2506 inhibits spike–wave discharges in a genetic animal model without affecting traditional convulsive tests via gliotransmission regulation

    PubMed Central

    Yamamura, Satoshi; Hoshikawa, Masamitsu; Dai, Kato; Saito, Hiromitsu; Suzuki, Noboru; Niwa, Osamu; Okada, Motohiro

    2013-01-01

    Background and Purpose Anticonvulsants have been developed according to the traditional neurotransmission imbalance hypothesis. However, the anticonvulsive pharmacotherapy currently available remains unsatisfactory. To develop new antiepileptic drugs with novel antiepileptic mechanisms, we have tested the antiepileptic actions of ONO-2506, a glial modulating agent, and its effects on tripartite synaptic transmission. Experimental Approach Dose-dependent effects of ONO-2506 on maximal-electroshock seizure (MES), pentylenetetrazol-induced seizure (PTZ) and epileptic discharge were determined in a genetic model of absence epilepsy in mice (Cacna1atm2Nobs/tm2Nobs strain). Antiepileptic mechanisms of ONO-2506 were analysed by examining the interaction between ONO-2506 and transmission-modulating toxins (tetanus toxin, fluorocitrate, tetrodotoxin) on release of l-glutamate, d-serine, GABA and kynurenic acid in the medial-prefrontal cortex (mPFC) of freely moving rats using microdialysis and primary cultured rat astrocytes. Key Results ONO-2506 inhibited spontaneous epileptic discharges in Cacna1atm2Nobs/tm2Nobs mice without affecting MES or PTZ. Given systemically, ONO-2506 increased basal release of GABA and kynurenic acid in the mPFC through activation of both neuronal and glial exocytosis, but inhibited depolarization-induced releases of all transmitters. ONO-2506 increased basal glial release of kynurenic acid without affecting those of l-glutamate, d-serine or GABA. However, ONO-2506 inhibited AMPA-induced releases of l-glutamate, d-serine, GABA and kynurenic acid. Conclusions and Implications ONO-2506 did not affect traditional convulsive tests but markedly inhibited epileptic phenomena in the genetic epilepsy mouse model. ONO-2506 enhanced release of inhibitory neuro- and gliotransmitters during the resting stage and inhibited tripartite transmission during the hyperactive stage. The results suggest that ONO-2506 is a novel potential glial-targeting antiepileptic

  16. New Regulations Affect School Debt Financing.

    ERIC Educational Resources Information Center

    Olson, Carol Duane

    1993-01-01

    Provides an overview of changes in Treasury Regulations as they affect school debt financing, including bond and note construction and acquisition issues, other types of equipment and property financing, as well as tax and revenue anticipation notes for working capital needs. (MLF)

  17. Legislation: Legislation and Regulations Affecting Libraries in 2002; Legislation and Regulations Affecting Publishing in 2002.

    ERIC Educational Resources Information Center

    Sheketoff, Emily; Costabile, Mary R.; Adler, Allan

    2003-01-01

    Reviews legislation and regulations affecting libraries and the publishing industry, including the Museum and Library Services Act; Office of Educational Research and Improvement (OERI); copyright; access to electronic government information; telecommunications and technology; electronic surveillance and privacy, including the USA Patriot Act;…

  18. The Affective Regulation of Social Interaction

    ERIC Educational Resources Information Center

    Clore, Gerald L.; Pappas, Jesse

    2007-01-01

    The recent publication of David Heise's "Expressive Order" (2007) provides an occasion for discussing some of the key ideas in Affect Control Theory. The theory proposes that a few dimensions of affective meaning provide a common basis for interrelating personal identities and social actions. It holds that during interpersonal interactions, social…

  19. Implicit emotion regulation affects outcome evaluation.

    PubMed

    Yang, Qiwei; Tang, Ping; Gu, Ruolei; Luo, Wenbo; Luo, Yue-jia

    2015-06-01

    Efficient implicit emotion regulation processes, which run without awareness, are important for human well-being. In this study, to investigate the influence of implicit emotion regulation on psychological and electrophysiological responses to gains and losses, participants were required to select between two Chinese four-character idioms to match the meaning of the third one before they performed a monetary gambling task. According to whether their meanings were related to emotion regulation, the idioms fell into two categories. Event-related potentials and self-rating emotional experiences to outcome feedback were recorded during the task. Priming emotion regulation reduced subjective emotional experience to both gains and losses and the amplitudes of the feedback-related negativity, while the P3 component was not influenced. According to these results, we suggest that the application of implicit emotion regulation effectively modulated the subjective emotional experience and the motivational salience of current outcomes without the cost of cognitive resources. This study implicates the potential significance of implicit emotion regulation in decision-making processes. PMID:25332404

  20. Gasoline Composition Regulations Affecting LUST Sites

    EPA Science Inventory

    Passage of the Clean Air Act Amendments in 1990 imposed requirements on gasoline composition in the United States. Impacts to ground water are affected by the provisions that required oxygenated additives and limited benzene concentration. Reformulated and oxygenated gasoline w...

  1. Self-regulation and Beyond: Affect Regulation and the Infant–Caregiver Dyad

    PubMed Central

    Taipale, Joona

    2016-01-01

    In the available psychological literature, affect regulation is fundamentally considered in terms of self-regulation, and according to this standard picture, the contribution of other people in our affect regulation has been viewed in terms of socially assisted self-regulation. The present article challenges this standard picture. By focusing on affect regulation as it unfolds in early infancy, it will be argued that instead of being something original and fundamental, self-regulation developmentally emerges from the basis of a further type of affect regulation. While infants’ capacities in recognizing, understanding, and modifying their own affective states are initially immature and undeveloped, affect regulation is initially managed by the other: it is initially the self, and not the other, that plays the role of an assistant in affect regulation. To capture this phenomenon, the concepts of “auto-matic,” “hetero-matic,” and “altero-matic” affect regulation will be introduced and their interrelations elaborated. By showing how the capacity of affective self-regulation, which is characteristic to maturity, is developmentally achieved by internalizing regulative functions that, at the outset of development, are managed by the caregiver, it will be argued that altero-matic affect regulation is an autonomous type of affect regulation and the developmental basis for self-regulation. PMID:27378984

  2. Early environment affects neuroendocrine regulation in adulthood

    PubMed Central

    Karlamangla, Arun S.; Friedman, Esther M.; Seeman, Teresa E.

    2011-01-01

    Animal and human research indicates that the early environment can exert effects on hypothalamic pituitary adrenal (HPA) axis functioning across the lifespan. Using data from the National Study of Midlife Development in the United States and the National Study of Daily Experience substudy, we identified curvilinear relations between adult reports of parental affection in childhood and adult diurnal cortisol rhythms. Reports of both very affectionate and very unaffectionate parental relations in childhood were associated with flatter diurnal rhythms, suggesting potential dysregulation of the HPA axis at both extremes of family environment. Participants in the bottom tertile showed more signs of HPA axis dysregulation than those in the top tertile. We discuss processes that may underlie these effects, with reference to the theory of allostatic load. PMID:20400490

  3. The role of personal self-regulation and regulatory teaching to predict motivational-affective variables, achievement, and satisfaction: a structural model.

    PubMed

    De la Fuente, Jesus; Zapata, Lucía; Martínez-Vicente, Jose M; Sander, Paul; Cardelle-Elawar, María

    2015-01-01

    The present investigation examines how personal self-regulation (presage variable) and regulatory teaching (process variable of teaching) relate to learning approaches, strategies for coping with stress, and self-regulated learning (process variables of learning) and, finally, how they relate to performance and satisfaction with the learning process (product variables). The objective was to clarify the associative and predictive relations between these variables, as contextualized in two different models that use the presage-process-product paradigm (the Biggs and DEDEPRO models). A total of 1101 university students participated in the study. The design was cross-sectional and retrospective with attributional (or selection) variables, using correlations and structural analysis. The results provide consistent and significant empirical evidence for the relationships hypothesized, incorporating variables that are part of and influence the teaching-learning process in Higher Education. Findings confirm the importance of interactive relationships within the teaching-learning process, where personal self-regulation is assumed to take place in connection with regulatory teaching. Variables that are involved in the relationships validated here reinforce the idea that both personal factors and teaching and learning factors should be taken into consideration when dealing with a formal teaching-learning context at university. PMID:25964764

  4. The role of personal self-regulation and regulatory teaching to predict motivational-affective variables, achievement, and satisfaction: a structural model

    PubMed Central

    De la Fuente, Jesus; Zapata, Lucía; Martínez-Vicente, Jose M.; Sander, Paul; Cardelle-Elawar, María

    2014-01-01

    The present investigation examines how personal self-regulation (presage variable) and regulatory teaching (process variable of teaching) relate to learning approaches, strategies for coping with stress, and self-regulated learning (process variables of learning) and, finally, how they relate to performance and satisfaction with the learning process (product variables). The objective was to clarify the associative and predictive relations between these variables, as contextualized in two different models that use the presage-process-product paradigm (the Biggs and DEDEPRO models). A total of 1101 university students participated in the study. The design was cross-sectional and retrospective with attributional (or selection) variables, using correlations and structural analysis. The results provide consistent and significant empirical evidence for the relationships hypothesized, incorporating variables that are part of and influence the teaching–learning process in Higher Education. Findings confirm the importance of interactive relationships within the teaching–learning process, where personal self-regulation is assumed to take place in connection with regulatory teaching. Variables that are involved in the relationships validated here reinforce the idea that both personal factors and teaching and learning factors should be taken into consideration when dealing with a formal teaching–learning context at university. PMID:25964764

  5. Affect Regulation as a Mediator of Attachment and Deliberate Self-Harm

    ERIC Educational Resources Information Center

    Kimball, Joan S.; Diddams, Margaret

    2007-01-01

    The authors used structural equation modeling to test the mediational role of affect regulation on attachment and deliberate self-harm in 216 undergraduates. Results suggest that affect regulation mediates the relationship between attachment and deliberate self-harm, providing support for the theoretical importance of attachment and affect…

  6. Extending Extant Models of the Pathogenesis of Borderline Personality Disorder to Childhood Borderline Personality Symptoms: The Roles of Affective Dysfunction, Disinhibition, and Self-and Emotion-Regulation Deficits

    PubMed Central

    Gratz, Kim L.; Tull, Matthew T.; Reynolds, Elizabeth K.; Bagge, Courtney L.; Latzman, Robert D.; Daughters, Stacey B.; Lejuez, C. W.

    2010-01-01

    Although research has been conducted on the course, consequences, and correlates of borderline personality disorder (BPD), little is known about its emergence in childhood, and no studies have examined the extent to which theoretical models of the pathogenesis of BPD in adults are applicable to the correlates of borderline personality symptoms in children. The goal of this study was to examine the interrelationships between two BPD-relevant personality traits (affective dysfunction and disinhibition), self- and emotion regulation deficits, and childhood borderline personality symptoms among 263 children aged 9 to 13. We predicted that affective dysfunction, disinhibition, and their interaction would be associated with childhood borderline personality symptoms, and that self- and emotion-regulation deficits would mediate these relationships. Results provided support for the roles of both affective dysfunction and disinhibition (in the form of sensation seeking) in childhood borderline personality symptoms, as well as their hypothesized interaction. Further, both self- and emotion-regulation deficits partially mediated the relationship between affective dysfunction and childhood borderline personality symptoms. Finally, results provided evidence of different gender-based pathways to childhood borderline personality symptoms, suggesting that models of BPD among adults are more relevant to understanding the factors associated with borderline personality symptoms among girls than boys. PMID:19825268

  7. Notch signaling affects biliary fibrosis via transcriptional regulation of RBP-jκ in an animal model of chronic liver disease

    PubMed Central

    Lee, Sun-Jae; Kim, Kyung-Hyun; Pak, Sok Cheon; Kang, Yu-Na; Yoon, Ghil-Suk; Park, Kwan-Kyu

    2015-01-01

    Liver repair in patients with a chronic liver disease requires the orchestrated action of epithelial, mesenchymal, and inflammatory cells. Notch components are expressed in both the epithelial and mesenchymal compartments of the adult liver and are differentially regulated after injury. However, the functional role of Notch signaling in regulating epithelial/mesenchymal cross-talk during fibrogenic pathologic repair remains unknown. The aim of this study was to investigate how proliferation of the bile duct influences biliary fibrosis and to recognize the effect of inhibiting Notch signaling in biliary fibrotic tissue of the injured liver. We designed a synthetic decoy oligodeoxynucleotide (ODN) for recombination signal binding protein immunoglobulin kappa J (RBP-jκ), which is a common DNA-binding partner of Notch receptors. The effect of blocking RBP-jκ on fibrogenesis was assessed in the 3,5-Diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet mouse model. We observed the reduced fibrosis and decreased expression of associated signaling molecules after the RBP-jκ decoy ODN treatment. These data demonstrate that Notch signaling may play an important role in progression of ductular reaction and fibrosis. Further studies are required to unveil how ductular cells interact with other liver cell types, such as hepatic stellate cells or Kupffer cells,in patients with cholestatic liver diseases based on Notch signaling. These results suggest that controlling the ductular reaction using a synthetic ring type decoy RBP-jκ ODN will help develop a novel therapeutic approach targeting biliary fibrosis in patients with chronic liver diseases. PMID:26722458

  8. [The Affect Experience and Affect Regulation Q-Sort Test (AREQ): validation and short version].

    PubMed

    Löffler-Stastka, Henriette; Stigler, Katharina

    2011-05-01

    Affect experience and affect regulation are based on varying concepts and the integration of this constructs is discussed controversy. The AREQ - Affect Experience and Affect Regulation Q-sort Test, an expert rating, covers the need of an integrated method to explore the emotional functioning of patients. This is the validation of the german version of the AREQ. Based on statistical considerations and in order to create a practicable and time efficient instrument, which is necessary to display the course and process of a therapy, we created a short version of the AREQ. In this short version only significant items are included, and therefore the time for the implementation is much shorter. The results of the statistical calculations show better psychometric properties for the short version. Especially the scales, which are defined by the original version, show better reliability and account in different samples for 60-73% of the variance. PMID:20845255

  9. Compassion-based emotion regulation up-regulates experienced positive affect and associated neural networks.

    PubMed

    Engen, Haakon G; Singer, Tania

    2015-09-01

    Emotion regulation research has primarily focused on techniques that attenuate or modulate the impact of emotional stimuli. Recent evidence suggests that this mode regulation can be problematic in the context of regulation of emotion elicited by the suffering of others, resulting in reduced emotional connectedness. Here, we investigated the effects of an alternative emotion regulation technique based on the up-regulation of positive affect via Compassion-meditation on experiential and neural affective responses to depictions of individuals in distress, and compared these with the established emotion regulation strategy of Reappraisal. Using fMRI, we scanned 15 expert practitioners of Compassion-meditation either passively viewing, or using Compassion-meditation or Reappraisal to modulate their emotional reactions to film clips depicting people in distress. Both strategies effectively, but differentially regulated experienced affect, with Compassion primarily increasing positive and Reappraisal primarily decreasing negative affect. Imaging results showed that Compassion, relative to both passive-viewing and Reappraisal increased activation in regions involved in affiliation, positive affect and reward processing including ventral striatum and medial orbitfrontal cortex. This network was shown to be active prior to stimulus presentation, suggesting that the regulatory mechanism of Compassion is the stimulus-independent endogenous generation of positive affect. PMID:25698699

  10. A Randomized Clinical Trial Comparing Affect Regulation and Social Problem-Solving Psychotherapies for Mothers with Victimization-Related PTSD

    ERIC Educational Resources Information Center

    Ford, Julian D.; Steinberg, Karen L.; Zhang, Wanli

    2011-01-01

    Addressing affect dysregulation may provide a complementary alternative or adjunctive approach to the empirically supported trauma memory processing models of cognitive behavior therapy (CBT) for posttraumatic stress disorder (PTSD). A CBT designed to enhance affect regulation without trauma memory processing--trauma affect regulation: guide for…

  11. Mountaineering as affect regulation: the moderating role of self-regulation strategies.

    PubMed

    Castanier, Carole; Le Scanff, Christine; Woodman, Tim

    2011-01-01

    We investigated the change in mountaineers' affect from pre- to post-mountain route and the moderating role of self-regulation strategies in this process. First, we hypothesized that engagement in a high-risk sport such as mountaineering would lead to a decrease in negative affect and an increase in positive affect and that this affect regulation would be moderated by self-regulation strategies (escape from self-awareness and compensation). Second, we predicted that the self-regulation affect process would be specifically associated with high-risk sport rather than sport generally. One hundred and five mountaineers and 73 judokas completed the Risk and Excitement Inventory and the Positive and Negative Emotions Scale before and after completing their activity (mountain route or judo fight). Regression analyses revealed that anxiety significantly decreased from pre- to post-mountain route and that the self-regulation of escape from awareness yielded a significantly greater anxiety decrease. No such interaction emerged for the compensation strategy and no effects were revealed for judokas. Results are discussed in terms of the specificity of the high-risk sport domain in its ability to serve an affect regulation function for those individuals who seek to escape from self-awareness. PMID:20397078

  12. Goal regulation across time: the effects of feedback and affect.

    PubMed

    Ilies, Remus; Judge, Timothy A

    2005-05-01

    This research focused on the processes individuals use to regulate their goals across time. Two studies examined goal regulation following task performance with 6 samples of participants in a series of 8-trial task performance experiments. The experiments involved: (a) 3 task types, (b) 2 goal types, and (c) actual or manipulated performance feedback referring to the focal participant's own performance or to the participant's performance compared with others' performance. Applying multilevel methods, the authors examined (a) how performance feedback influences subsequent goals within individuals across both negative and positive performance feedback ranges, and (b) the mediating role of affect in explaining the relationship between feedback and subsequent goal setting. Results showed that participants adjusted their goals downwardly following negative feedback and created positive goal-performance discrepancies by raising their goals following positive feedback. In each sample, affect mediated substantial proportions of the feedback-goals relationship within individuals. PMID:15910142

  13. Models of Affective Decision Making

    PubMed Central

    Charpentier, Caroline J.; De Neve, Jan-Emmanuel; Li, Xinyi; Roiser, Jonathan P.; Sharot, Tali

    2016-01-01

    Intuitively, how you feel about potential outcomes will determine your decisions. Indeed, an implicit assumption in one of the most influential theories in psychology, prospect theory, is that feelings govern choice. Surprisingly, however, very little is known about the rules by which feelings are transformed into decisions. Here, we specified a computational model that used feelings to predict choices. We found that this model predicted choice better than existing value-based models, showing a unique contribution of feelings to decisions, over and above value. Similar to the value function in prospect theory, our feeling function showed diminished sensitivity to outcomes as value increased. However, loss aversion in choice was explained by an asymmetry in how feelings about losses and gains were weighted when making a decision, not by an asymmetry in the feelings themselves. The results provide new insights into how feelings are utilized to reach a decision. PMID:27071751

  14. Affect Regulation in Families: A Link between Marital Conflict and Child Behavior.

    ERIC Educational Resources Information Center

    Guttentag, Cathy; Alex, Stefany

    This study examined parents' and children's affect regulation skills and constructive behavior to test whether a modeling mechanism or a parent-child interaction mechanism best accounted for children's behavior. Thirty-six married couples and their 4- to 7-year-old children participated in the study. The families were asked to play a board game…

  15. European Regulation Affecting Nanomaterials - Review of Limitations and Future Recommendations

    PubMed Central

    Hansen, Steffen Foss; Baun, Anders

    2012-01-01

    After learning about the potential risks associated with various specific nanomaterials, concerns have been raised about adequacy of existing regulation in Europe and what should be done to address any potential regulatory gaps related to nanomaterials. Understanding the limitations of the current regulation in regard to nanomaterials is a starting point in a democratic and transparent process towards adapting existing laws and facilitating an informed discussion about which kind of regulatory options best address the identified limitations. In the following we will introduce key pieces of European legislation affecting nanomaterials, analyze their limitations, and provide a number of recommendations on how these can be overcome. We find that, although nanomaterials are in principle covered by the scope of many of the existing legislative frameworks, it is often unclear, if current regulations are actually applicable when it comes to specific nanomaterials and their diverse applications. Main limitations seem to be: that requirements to do safety evaluations are triggered by production volumes by tonnage not tailored to the nanoscale, the profound lack of (eco)toxicological data, and that thresholds values and occupational exposure limits cannot be established with existing methodologies. PMID:22942870

  16. Using interpersonal affect regulation in simulated healthcare consultations: an experimental investigation of self-control resource depletion

    PubMed Central

    Martínez-Íñigo, David; Mercado, Francisco; Totterdell, Peter

    2015-01-01

    Controlled Interpersonal Affect Regulation –the process of deliberately influencing the internal feeling states of others– occurs in a variety of interpersonal relationships and contexts. An incipient corpus of research shows that interpersonal affect regulation can be characterized as a goal-directed behavior that uses self-control processes which, according to the strength model of self-regulation, consumes a limited resource that is also used by other self-control processes. Using interpersonal affect-improving and affect-worsening regulation strategies can increase agent’s resource depletion but there is reason to think that effects will partially rely on target’s feedback in response to the regulation. Using a healthcare paradigm, an experiment was conducted to test the combined effects of interpersonal affect regulation use and patient feedback on healthcare workers’ resource depletion, measured as self-reported experienced and expected emotional exhaustion, and persistence on a self-regulation task. Medical students (N = 78) were randomly assigned to a 2(interpersonal affect regulation: affect-worsening vs. affect-improving) × 2(patients’ feedback: positive vs. negative) factorial between-subjects design and given instructions to play the role of doctors in interactions with two professional actors trained to act as patients. Analysis of covariance showed that affect-worsening was more depleting than affect-improving for all measures, whereas the recovery effects of positive feedback varied depending on strategy type and measure. The findings confirm the characterization of interpersonal affect regulation as potentially depleting, but suggest that the correspondence between the agent’s strategy and the target’s response needs to be taken into consideration. Use of affect-improving and positive feedback showed positive effects on self-rated performance, indicating that interpersonal affect regulation is relevant for organizational as well as

  17. Affect Regulation and Purging: An Ecological Momentary Assessment Study in Purging Disorder

    PubMed Central

    Haedt-Matt, Alissa A.; Keel, Pamela K.

    2015-01-01

    Research suggests that affect may play an important role in the propensity to purge among women with Purging Disorder (PD). However, prior work has been constrained to cross-sectional or laboratory designs which impact temporal interpretations and ecological validity. This study examined the role of negative affect (NA) and positive affect (PA) in triggering and maintaining purging in PD using ecological momentary assessment. Women with PD (N=24) made multiple daily ratings of affect and behavior for two weeks. Multilevel models examined associations between affect and purging at different levels of analysis, including a novel analytic approach to address the specificity of changes in affect relative to purging behavior by comparing trajectories of change on purge versus non-purge days. For trajectories of affect over time, NA increased before purging and decreased following purging on purge days; however, only the decrease in NA following purging was significantly different from the trajectory of NA on non-purge days. Conversely, PA failed to increase before purging on purge days compared to a matched time-point on non-purge days. These findings suggest unique roles of PA in triggering and NA in maintaining purging in PD and support models in which purging functions to regulate affect. For comparisons of ratings before and after purging, NA increased and PA decreased after purging, highlighting how different analytic strategies produce different findings requiring integration into affect regulation models. These data provide insight into why women with PD purge after consuming normal amounts of food, a crucial first step for developing effective interventions. PMID:25688426

  18. Adult Antisocial Behavior and Affect Regulation among Primary Crack/Cocaine-Using Women

    ERIC Educational Resources Information Center

    Litt, Lisa Caren; Hien, Denise A.; Levin, Deborah

    2003-01-01

    The relationship between deficits in affect regulation and Adult Antisocial Behavior (ASB) in primary crack/cocaine-using women was explored in a sample of 80 inner-city women. Narrative early memories were coded for two components of affect regulation, Affect Tolerance and Affect Expression, using the Epigenetic Assessment Rating Scale (EARS;…

  19. Mathematical Models of Gene Regulation

    NASA Astrophysics Data System (ADS)

    Mackey, Michael C.

    2004-03-01

    This talk will focus on examples of mathematical models for the regulation of repressible operons (e.g. the tryptophan operon), inducible operons (e.g. the lactose operon), and the lysis/lysogeny switch in phage λ. These ``simple" gene regulatory elements can display characteristics experimentally of rapid response to perturbations and bistability, and biologically accurate mathematical models capture these aspects of the dynamics. The models, if realistic, are always nonlinear and contain significant time delays due to transcriptional and translational delays that pose substantial problems for the analysis of the possible ranges of dynamics.

  20. Regulation of Expressive Behavior as Reflecting Affect Socialization.

    ERIC Educational Resources Information Center

    Saarni, Carolyn

    Regulated expressiveness (the modification of expressive behavior) is a complex phenomenon. Accomplished basically in four ways, regulated expressiveness has developmental dimensions, motivational precursors, and cognitive antecedents, including perspective-taking ability and the growth of self-awareness. Ability to regulate expressiveness appears…

  1. Manipulation of adenosine kinase affects sleep regulation in mice

    PubMed Central

    Palchykova, Svitlana; Winsky-Sommerer, Raphaelle; Shen, Hai-Ying; Boison, Detlev; Gerling, Andrea; Tobler, Irene

    2010-01-01

    Sleep and sleep intensity are enhanced by adenosine and its receptor agonists, while adenosine receptor antagonists induce wakefulness. Adenosine kinase (ADK) is the primary enzyme metabolizing adenosine in adult brain. To investigate whether adenosine metabolism or clearance affects sleep we recorded sleep in mice with engineered mutations in Adk. Adk-tg mice over-express a transgene encoding the cytoplasmic isoform of ADK in the brain, but lack the nuclear isoform of the enzyme. Wild-type mice and Adk+/− mice that have a 50% reduction of the cytoplasmic and the nuclear isoforms of ADK served as controls. Adk-tg mice showed a remarkable reduction of EEG power in low frequencies in all vigilance states and in theta activity (6.25–11 Hz) in REM sleep and waking. Adk-tg mice were awake 58 min more per day than wild-type mice and spent significantly less time in REM sleep (102±3 vs 128±3 min in wild-type). After sleep deprivation slow-wave activity (0.75–4 Hz), the intensity component of NREM sleep, increased significantly less in Adk-tg mice and their slow-wave energy was reduced. In contrast, the vigilance states and EEG spectra of Adk+/− and wild-type mice did not differ. Our data suggest that over-expression of the cytoplasmic isoform of ADK is sufficient to alter sleep physiology. ADK might orchestrate neurotransmitter pathways involved in the generation of EEG oscillations and regulation of sleep. PMID:20881134

  2. Does regulating others' feelings influence people's own affective well-being?

    PubMed

    Niven, Karen; Totterdell, Peter; Holman, David; Headley, Tara

    2012-01-01

    Individuals in a variety of social contexts try to regulate other people's feelings, but how does this process affect the regulators themselves? This research aimed to establish a relationship between people's use of interpersonal affect regulation and their own affective well-being. In a field study, self- and other-reported data were collected from prisoners and staff members in a therapeutic prison using two surveys separated in time. In a laboratory study, a student sample reported their affect before and after attempting to influence the feelings of talent show contestants in a role-play task. The results of both studies indicated congruent associations between the use of affect-improving and affect-worsening interpersonal affect regulation and strategy agents' affective well-being. Our findings highlight that, when performing interpersonal affect regulation, people may not be immune from the effects of their own actions. PMID:22468424

  3. The roles of the amygdala in the affective regulation of body, brain, and behaviour

    NASA Astrophysics Data System (ADS)

    Mirolli, Marco; Mannella, Francesco; Baldassarre, Gianluca

    2010-09-01

    Despite the great amount of knowledge produced by the neuroscientific literature on affective phenomena, current models tackling non-cognitive aspects of behaviour are often bio-inspired but rarely bio-constrained. This paper presents a theoretical account of affective systems centred on the amygdala (Amg). This account aims to furnish a general framework and specific pathways to implement models that are more closely related to biological evidence. The Amg, which receives input from brain areas encoding internal states, innately relevant stimuli, and innately neutral stimuli, plays a fundamental role in the motivational and emotional processes of organisms. This role is based on the fact that Amg implements the two associative processes at the core of Pavlovian learning (conditioned stimulus (CS)-unconditioned stimulus (US) and CS-unconditioned response (UR) associations), and that it has the capacity of modulating these associations on the basis of internal states. These functionalities allow the Amg to play an important role in the regulation of the three fundamental classes of affective responses (namely, the regulation of body states, the regulation of brain states via neuromodulators, and the triggering of a number of basic behaviours fundamental for adaptation) and in the regulation of three high-level cognitive processes (namely, the affective labelling of memories, the production of goal-directed behaviours, and the performance of planning and complex decision-making). Our analysis is conducted within a methodological approach that stresses the importance of understanding the brain within an evolutionary/adaptive framework and with the aim of isolating general principles that can potentially account for the wider possible empirical evidence in a coherent fashion.

  4. Interpersonal dysfunction and affect-regulation difficulties in disordered eating among men and women.

    PubMed

    Ambwani, Suman; Slane, Jennifer D; Thomas, Katherine M; Hopwood, Christopher J; Grilo, Carlos M

    2014-12-01

    Although several studies suggest that negative affect and interpersonal problems serve as important contributors for eating-related problems, much of this research has been conducted among women and less is known about their roles in precipitating and maintaining eating problems among men. Previous studies with undergraduate men suggest that difficulties in emotion regulation are associated with disordered eating even after controlling for differences in body mass index (BMI) and negative affect. The present study sought to replicate these findings and extend them to assess any unique variance explained by problems in interpersonal functioning among both men and women. Participants were men (n=213) and women (n=521) undergraduates at a large Midwestern university who completed a demographic information form, the Eating Disorder Examination-Questionnaire (EDE-Q), the Difficulties in Emotion Regulation Scale (DERS), the Positive and Negative Affect Schedule, and the Inventory of Interpersonal Problems-Short Circumplex Form (IIP-SC). A series of hierarchical regression analyses indicated that DERS and IIP-SC significantly predicted EDE-Q global scores after controlling for variability in BMI and negative affect and that the results were similar for men and women. Our findings offer preliminary support for models that highlight emotional vulnerability and interpersonal problems for disordered eating for young adult men. Future research extending these findings among treatment-seeking samples and employing multi-method assessment would serve to further clarify the tenability of these theoretical models for both men and women. PMID:25194562

  5. Affect Regulation Training (ART) for Alcohol Use Disorders: Development of a Novel Intervention for Negative Affect Drinkers

    PubMed Central

    Stasiewicz, Paul R.; Bradizza, Clara M.; Schlauch, Robert C.; Coffey, Scott F.; Gulliver, Suzy B.; Gudleski, Gregory; Bole, Christopher W.

    2013-01-01

    Although negative affect is a common precipitant of alcohol relapse, there are few interventions for alcohol dependence that specifically target negative affect. In this Stage 1a/1b treatment development study, several affect regulation strategies (e.g., mindfulness, prolonged exposure, distress tolerance) were combined to create a new treatment supplement called Affect Regulation Training (ART), which could be added to enhance Cognitive-Behavioral Therapy (CBT) for alcohol dependence. A draft therapy manual was given to therapists and treatment experts before being administered to several patients who also provided input. After two rounds of manual development (Stage 1a), a pilot randomized clinical trial (N = 77) of alcohol-dependent outpatients who reported drinking often in negative affect situations was conducted (Stage 1b). Participants received 12-weekly, 90-minute sessions of either CBT for alcohol dependence plus ART (CBT + ART) or CBT plus a healthy lifestyles control condition (CBT + HLS). Baseline, end-of-treatment, and 3- and 6-month posttreatment interviews were conducted. For both treatment conditions, participant ratings of treatment satisfaction were high, with CBT + ART rated significantly higher. Drinking outcome results indicated greater reductions in alcohol use for CBT + ART when compared to CBT + HLS, with moderate effect sizes for percent days abstinent, drinks per day, drinks per drinking day, and percent heavy drinking days. Overall, findings support further research on affect regulation interventions for negative affect drinkers. PMID:23876455

  6. Economic Approaches to Estimating Benefits of Regulations Affecting Addictive Goods.

    PubMed

    Cutler, David M; Jessup, Amber I; Kenkel, Donald S; Starr, Martha A

    2016-05-01

    The question of how to evaluate lost consumer surplus in benefit-cost analyses has been contentious. There are clear health benefits of regulations that curb consumption of goods with health risks, such as tobacco products and foods high in fats, calories, sugar, and sodium. Yet, if regulations cause consumers to give up goods they like, the health benefits they experience may be offset by some utility loss, which benefit-cost analyses of regulations need to take into account. This paper lays out the complications of measuring benefits of regulations aiming to curb consumption of addictive and habitual goods, rooted in the fact that consumers' observed demand for such goods may not be in line with their true preferences. Focusing on the important case of tobacco products, the paper describes four possible approaches for estimating benefits when consumers' preferences may not be aligned with their behavior, and identifies one as having the best feasibility for use in applied benefit-cost analyses in the near term. PMID:27102854

  7. Attachment and Affect Regulation in Depressed Mothers and Their Adolescent Daughters.

    ERIC Educational Resources Information Center

    Homann, Erika

    This study assessed the associations of maternal attachment classification with mother and daughter depression and affect regulation, with the hypothesis that affect regulation might mediate between attachment and depression both within and between generations. Twenty-five dysthymic mothers, 25 non-depressed mothers, and their adolescent…

  8. Developmental regulation with progressive vision loss: Use of control strategies and affective well-being.

    PubMed

    Schilling, Oliver K; Wahl, Hans-Werner; Boerner, Kathrin; Horowitz, Amy; Reinhardt, Joann P; Cimarolli, Verena R; Brennan-Ing, Mark; Heckhausen, Jutta

    2016-04-01

    The present study addresses older adults' developmental regulation when faced with progressive and irreversible vision loss. We used the motivational theory of life span development as a conceptual framework and examined changes in older adults' striving for control over everyday goal achievement, and their association with affective well-being, in a sample of 364 older adults diagnosed with age-related macular degeneration. Using longitudinal data from 5 occasions at 6-month intervals, we examined intraindividual change in control strategies, and how it was related to change in affective well-being, in terms of self-rated happiness and depressive symptoms. Mixed model analyses confirmed our hypotheses that (a) intraindividual change, particularly in selective primary control and in compensatory secondary control (CSC), predict change toward higher happiness ratings and lower depression; and (b) as functional abilities (instrumental activities of daily living) declined, CSC became increasingly predictive of better affective well-being. Overall, the findings suggest that CSC strategies are essential for maintaining affective well-being when physical functioning declines. Intensified selective primary control striving may be effective to achieve goals that have become difficult to reach but are not associated with affective well-being, possibly because struggling with difficulties undermines the experience of enjoyable mastery. In contrast, goal adjustments and self-protective thinking may help to find pleasure even from restricted daily activities. (PsycINFO Database Record PMID:26845507

  9. Multifaceted emotion regulation, stress and affect in mothers of young children.

    PubMed

    Deater-Deckard, Kirby; Li, Mengjiao; Bell, Martha Ann

    2016-01-01

    We tested a novel multi-component emotion self-regulation construct that captured physiological (vagal tone), cognitive (reappraisal) and temperament (effortful control) aspects of emotion regulation (ER) as a moderator of the link between more stressors and greater negative/less positive affectivity (NA and PA). A socio-economically diverse sample of 151 women with young children completed questionnaires and a laboratory visit (including cognitive and parent-child interaction tasks and vagal tone measurement). Women with more stressors had more NA and less PA. Furthermore, for NA only, having more stressors was substantially associated with NA but only among women with the lowest ER. This pattern was evident for the composite as well as individual indicators of ER. Results were not attributable to individual differences in executive function. Findings are discussed in light of the diathesis-stress model of stress and coping. PMID:25759238

  10. Interactive regulation of affect in postpartum depressed mothers and their infants: an overview.

    PubMed

    Reck, Corinna; Hunt, Aoife; Fuchs, Thomas; Weiss, Robert; Noon, Andrea; Moehler, Eva; Downing, George; Tronick, Edward Z; Mundt, Christoph

    2004-01-01

    Specific patterns of interaction emerging in the first months of life are related to processes regulating mutual affects in the mother-child dyad. Particularly important for the dyad are the matching and interactive repair processes. The interaction between postpartum depressed mothers and their children is characterized by a lack of responsiveness, by passivity or intrusiveness, withdrawal and avoidance, as well as a low level of positive expression of affect. Thus, an impaired capability to regulate the child's affect has been demonstrated in depressed mothers. Maternal aggression, neglect toward infants, infanticidal thoughts, as well as infanticidal behavior are mainly linked to severe postpartum depression, especially with psychotic symptoms. The findings on mother-child interaction reported in this paper are based on mothers with mild to moderate depressive disorders without psychotic symptoms. Considering the stability of interaction patterns in the course of depressive illness as well as the long-term consequences of these interactions, it seems surprising that there are still few systematic studies of depressed mothers interacting with their infants. In connection with an overview on these issues, treatment models for parent-infant psychotherapy are discussed. PMID:15539778

  11. Factors affecting the regulation of pacing: current perspectives

    PubMed Central

    Mauger, Alexis R

    2014-01-01

    During prolonged dynamic and rhythmic exercise, muscular pain and discomfort arises as a result of an increased concentration of deleterious metabolites. Sensed by peripheral nociceptors and transmitted via afferent feedback to the brain, this provides important information regarding the physiological state of the muscle. These sensations ultimately contribute to what is termed “exercise-induced pain”. Despite being well recognized by athletes and coaches, and suggested to be integral to exercise performance, this construct has largely escaped attention in experimental work. This perspective article highlights the current understanding of pacing in endurance performance, and the causes of exercise-induced pain. A new perspective is described, which proposes how exercise-induced pain may be a contributing factor in helping individuals to regulate their work rate during exercise and thus provides an important construct in pacing. PMID:25228823

  12. Post-Traumatic Stress Disorder Symptoms, Underlying Affective Vulnerabilities, and Smoking for Affect Regulation

    PubMed Central

    Mathew, Amanda R.; Cook, Jessica W.; Japuntich, Sandra J.; Leventhal, Adam M.

    2015-01-01

    Background and Objectives Post-traumatic stress disorder (PTSD) is overrepresented among cigarette smokers. It has been hypothesized that those with PTSD smoke to alleviate negative affect and counteract deficient positive affect commonly associated with the disorder; however, limited research has examined associations between PTSD symptoms, smoking motives, and affective vulnerability factors. In the current study, we examined (1) whether PTSD symptoms were associated with positive reinforcement and negative reinforcement smoking motives; and (2) whether two affective vulnerability factors implicated in PTSD—anxiety sensitivity and anhedonia—mediated relationships between PTSD symptoms and smoking motives. Methods Data were drawn from a community sample of non-treatment-seeking smokers recruited without regard for trauma history (N = 342; 10+cig/day). We used the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C) to assess overall PTSD symptom severity as well as individual PTSD subfactors. Results Overall, PTSD symptom severity was significantly associated with negative reinforcement, but not positive reinforcement, smoking motives. Variation in anxiety sensitivity significantly mediated the relation between PTSD symptom severity and negative reinforcement smoking motives, whereas anhedonia did not. Regarding PTSD subfactors, emotional numbing was the only PTSD subfactor associated with smoking rate, while re-experiencing symptoms were uniquely associated with both positive reinforcement and negative reinforcement smoking motives. Conclusions and Scientific Significance Findings suggest that anxiety sensitivity may be an important feature associated with PTSD that enhances motivation to smoke for negative reinforcement purposes. Smoking cessation interventions that alleviate anxiety sensitivity and enhance coping with negative affect may be useful for smokers with elevated PTSD symptoms. PMID:25823634

  13. Affect in the "Communicative" Classroom: A Model.

    ERIC Educational Resources Information Center

    Acton, William

    Recent research on affective variables and classroom second language learning suggests that: (1) affective variables are context-sensitive in at least two ways; (2) attitudes are contagious, and the general attitude of students can be influenced from various directions; (3) research in pragmatics, discourse analysis, and communicative functions…

  14. A Hierarchical Latent Stochastic Differential Equation Model for Affective Dynamics

    ERIC Educational Resources Information Center

    Oravecz, Zita; Tuerlinckx, Francis; Vandekerckhove, Joachim

    2011-01-01

    In this article a continuous-time stochastic model (the Ornstein-Uhlenbeck process) is presented to model the perpetually altering states of the core affect, which is a 2-dimensional concept underlying all our affective experiences. The process model that we propose can account for the temporal changes in core affect on the latent level. The key…

  15. 77 FR 467 - Notice of Tribal Consultation Meetings Regarding How the Current SACWIS Regulations Affect Tribes...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-05

    ... Meetings Regarding How the Current SACWIS Regulations Affect Tribes Administering a Title IV-E Program... CONTACT: If you have questions about this process, or want further information about current...

  16. Latent Differential Equation Modeling of Self-Regulatory and Coregulatory Affective Processes

    ERIC Educational Resources Information Center

    Steele, Joel S.; Ferrer, Emilio

    2011-01-01

    We examine emotion self-regulation and coregulation in romantic couples using daily self-reports of positive and negative affect. We fit these data using a damped linear oscillator model specified as a latent differential equation to investigate affect dynamics at the individual level and coupled influences for the 2 partners in each couple.…

  17. Affect as Information in Persuasion: A Model of Affect Identification and Discounting

    PubMed Central

    Albarracín, Dolores; Kumkale, G. Tarcan

    2016-01-01

    Three studies examined the implications of a model of affect as information in persuasion. According to this model, extraneous affect may have an influence when message recipients exert moderate amounts of thought, because they identify their affective reactions as potential criteria but fail to discount them as irrelevant. However, message recipients may not use affect as information when they deem affect irrelevant or when they do not identify their affective reactions at all. Consistent with this curvilinear prediction, recipients of a message that either favored or opposed comprehensive exams used affect as a basis for attitudes in situations that elicited moderate thought. Affect, however, had no influence on attitudes in conditions that elicited either large or small amounts of thought. PMID:12635909

  18. Control, Motivation, Affect, and Strategic Self-Regulation in the College Classroom: A Multidimensional Phenomenon

    ERIC Educational Resources Information Center

    Shell, Duane F.; Husman, Jenefer

    2008-01-01

    This study of 397 undergraduate students examined relations between self-reported control, goal orientation, future time perspective, affect, and strategic self-regulation. Five patterns were found in three canonical dimensions. The high end of bipolar Dimension 1 linked high self-regulated strategy use and study effort to high self-efficacy,…

  19. Drawing versus Writing: The Role of Preference in Regulating Short-Term Affect

    ERIC Educational Resources Information Center

    Drake, Jennifer E.; Hodge, Adeline

    2015-01-01

    In a pilot study we investigated whether the most effective medium for regulating short-term affect depends on one's preference for drawing or writing, and also investigated the emotion regulation strategy (distraction versus expression) spontaneously chosen when drawing and writing. Eighty undergraduates indicated their preference for drawing or…

  20. Toddler Emotion Regulation with Mothers and Fathers: Temporal Associations between Negative Affect and Behavioral Strategies

    ERIC Educational Resources Information Center

    Ekas, Naomi V.; Braungart-Rieker, Julia M.; Lickenbrock, Diane M.; Zentall, Shannon R.; Maxwell, Scott M.

    2011-01-01

    The present study investigated temporal associations between putative emotion regulation strategies and negative affect in 20-month-old toddlers. Toddlers' parent-focused, self-distraction, and toy-focused strategies, as well as negative affect, were rated on a second-by-second basis during laboratory parent-toddler interactions. Longitudinal…

  1. Safe Thinking and Affect Regulation (STAR): Human Immunodeficiency Virus Prevention in Alternative/Therapeutic Schools

    ERIC Educational Resources Information Center

    Brown, Larry K.; Nugent, Nicole R.; Houck, Christopher D.; Lescano, Celia M.; Whiteley, Laura B.; Barker, David; Viau, Lisa; Zlotnick, Caron

    2011-01-01

    Objective: To evaluate the effectiveness of Safe Thinking and Affect Regulation (STAR), a 14-session HIV-prevention program for adolescents at alternative/therapeutic schools. Because these youth frequently have difficulties with emotions and cognitions, it was designed to improve sexuality-specific affect management and cognitive monitoring, as…

  2. Individual differences in vagal regulation moderate associations between daily affect and daily couple interactions.

    PubMed

    Diamond, Lisa M; Hicks, Angela M; Otter-Henderson, Kimberly D

    2011-06-01

    Previous research suggests that cardiac vagal regulation (indexed by respiratory sinus arrhythmia, or RSA) provides a physiological substrate for affect regulation, which presumably underlies adaptive interpersonal functioning.The authors tested these associations in the context of daily interactions between 68 cohabiting couples. Participants underwent a laboratory assessment of RSA during rest and also during a series of psychological stressors. Subsequently, they kept daily measures of affect and interaction quality for 21 days. Individual differences in baseline and stress levels of RSA moderated within-person associations between daily affect and the quality of couple interactions. The pattern of results differed for women versus men. Men with lower vagal tone or higher vagal reactivity had stronger associations between daily negative affect and daily negative interactions, and men with higher vagal tone had more positive daily interactions overall. Women with higher vagal tone had stronger associations between daily positive affect and daily positive interactions. PMID:21393615

  3. The Influence of a Model's Reinforcement Contingency and Affective Response on Children's Perceptions of the Model

    ERIC Educational Resources Information Center

    Thelen, Mark H.; And Others

    1977-01-01

    Assesses the influence of model consequences on perceived model affect and, conversely, assesses the influence of model affect on perceived model consequences. Also appraises the influence of model consequences and model affect on perceived model attractiveness, perceived model competence, and perceived task attractiveness. (Author/RK)

  4. Gene Regulation Networks for Modeling Drosophila Development

    NASA Technical Reports Server (NTRS)

    Mjolsness, E.

    1999-01-01

    This chapter will very briefly introduce and review some computational experiments in using trainable gene regulation network models to simulate and understand selected episodes in the development of the fruit fly, Drosophila Melanogaster.

  5. DEPTOR in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance

    PubMed Central

    Caron, Alexandre; Labbé, Sébastien M.; Mouchiroud, Mathilde; Huard, Renaud; Richard, Denis

    2016-01-01

    We have recently demonstrated that specific overexpression of DEP-domain containing mTOR-interacting protein (DEPTOR) in the mediobasal hypothalamus (MBH) protects mice against high-fat diet-induced obesity, revealing DEPTOR as a significant contributor to energy balance regulation. On the basis of evidence that DEPTOR is expressed in the proopiomelanocortin (POMC) neurons of the MBH, the present study aimed to investigate whether these neurons mediate the metabolic effects of DEPTOR. Here, we report that specific DEPTOR overexpression in POMC neurons does not recapitulate any of the phenotypes observed when the protein was overexpressed in the MBH. Unlike the previous model, mice overexpressing DEPTOR only in POMC neurons 1) did not show differences in feeding behavior, 2) did not exhibit changes in locomotion activity and oxygen consumption, 3) did not show an improvement in systemic glucose metabolism, and 4) were not resistant to high-fat diet-induced obesity. These results support the idea that other neuronal populations are responsible for these phenotypes. Nonetheless, we observed a mild elevation in fasting blood glucose, insulin resistance, and alterations in liver glucose and lipid homeostasis in mice overexpressing DEPTOR in POMC neurons. Taken together, these results show that DEPTOR overexpression in POMC neurons does not affect energy balance regulation but could modulate metabolism through a brain-liver connection. PMID:27097662

  6. DEPTOR in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance.

    PubMed

    Caron, Alexandre; Labbé, Sébastien M; Mouchiroud, Mathilde; Huard, Renaud; Richard, Denis; Laplante, Mathieu

    2016-06-01

    We have recently demonstrated that specific overexpression of DEP-domain containing mTOR-interacting protein (DEPTOR) in the mediobasal hypothalamus (MBH) protects mice against high-fat diet-induced obesity, revealing DEPTOR as a significant contributor to energy balance regulation. On the basis of evidence that DEPTOR is expressed in the proopiomelanocortin (POMC) neurons of the MBH, the present study aimed to investigate whether these neurons mediate the metabolic effects of DEPTOR. Here, we report that specific DEPTOR overexpression in POMC neurons does not recapitulate any of the phenotypes observed when the protein was overexpressed in the MBH. Unlike the previous model, mice overexpressing DEPTOR only in POMC neurons 1) did not show differences in feeding behavior, 2) did not exhibit changes in locomotion activity and oxygen consumption, 3) did not show an improvement in systemic glucose metabolism, and 4) were not resistant to high-fat diet-induced obesity. These results support the idea that other neuronal populations are responsible for these phenotypes. Nonetheless, we observed a mild elevation in fasting blood glucose, insulin resistance, and alterations in liver glucose and lipid homeostasis in mice overexpressing DEPTOR in POMC neurons. Taken together, these results show that DEPTOR overexpression in POMC neurons does not affect energy balance regulation but could modulate metabolism through a brain-liver connection. PMID:27097662

  7. FMRP regulates multipolar to bipolar transition affecting neuronal migration and cortical circuitry.

    PubMed

    La Fata, Giorgio; Gärtner, Annette; Domínguez-Iturza, Nuria; Dresselaers, Tom; Dawitz, Julia; Poorthuis, Rogier B; Averna, Michele; Himmelreich, Uwe; Meredith, Rhiannon M; Achsel, Tilmann; Dotti, Carlos G; Bagni, Claudia

    2014-12-01

    Deficiencies in fragile X mental retardation protein (FMRP) are the most common cause of inherited intellectual disability, fragile X syndrome (FXS), with symptoms manifesting during infancy and early childhood. Using a mouse model for FXS, we found that Fmrp regulates the positioning of neurons in the cortical plate during embryonic development, affecting their multipolar-to-bipolar transition (MBT). We identified N-cadherin, which is crucial for MBT, as an Fmrp-regulated target in embryonic brain. Furthermore, spontaneous network activity and high-resolution brain imaging revealed defects in the establishment of neuronal networks at very early developmental stages, further confirmed by an unbalanced excitatory and inhibitory network. Finally, reintroduction of Fmrp or N-cadherin in the embryo normalized early postnatal neuron activity. Our findings highlight the critical role of Fmrp in the developing cerebral cortex and might explain some of the clinical features observed in patients with FXS, such as alterations in synaptic communication and neuronal network connectivity. PMID:25402856

  8. Count ratio model reveals bias affecting NGS fold changes

    PubMed Central

    Erhard, Florian; Zimmer, Ralf

    2015-01-01

    Various biases affect high-throughput sequencing read counts. Contrary to the general assumption, we show that bias does not always cancel out when fold changes are computed and that bias affects more than 20% of genes that are called differentially regulated in RNA-seq experiments with drastic effects on subsequent biological interpretation. Here, we propose a novel approach to estimate fold changes. Our method is based on a probabilistic model that directly incorporates count ratios instead of read counts. It provides a theoretical foundation for pseudo-counts and can be used to estimate fold change credible intervals as well as normalization factors that outperform currently used normalization methods. We show that fold change estimates are significantly improved by our method by comparing RNA-seq derived fold changes to qPCR data from the MAQC/SEQC project as a reference and analyzing random barcoded sequencing data. Our software implementation is freely available from the project website http://www.bio.ifi.lmu.de/software/lfc. PMID:26160885

  9. Count ratio model reveals bias affecting NGS fold changes.

    PubMed

    Erhard, Florian; Zimmer, Ralf

    2015-11-16

    Various biases affect high-throughput sequencing read counts. Contrary to the general assumption, we show that bias does not always cancel out when fold changes are computed and that bias affects more than 20% of genes that are called differentially regulated in RNA-seq experiments with drastic effects on subsequent biological interpretation. Here, we propose a novel approach to estimate fold changes. Our method is based on a probabilistic model that directly incorporates count ratios instead of read counts. It provides a theoretical foundation for pseudo-counts and can be used to estimate fold change credible intervals as well as normalization factors that outperform currently used normalization methods. We show that fold change estimates are significantly improved by our method by comparing RNA-seq derived fold changes to qPCR data from the MAQC/SEQC project as a reference and analyzing random barcoded sequencing data. Our software implementation is freely available from the project website http://www.bio.ifi.lmu.de/software/lfc. PMID:26160885

  10. Controlling illegal stimulants: a regulated market model

    PubMed Central

    Haden, Mark

    2008-01-01

    Prohibition of illegal drugs is a failed social policy and new models of regulation of these substances are needed. This paper explores a proposal for a post-prohibition, public health based model for the regulation of the most problematic drugs, the smokable and injectable stimulants. The literature on stimulant maintenance is explored. Seven foundational principles are suggested that could support this regulatory model of drug control that would reduce both health and social problems related to illegal stimulants. Some details of this model are examined and the paper concludes that drug policies need to be subject to research and based on evidence. PMID:18215317

  11. Factors affecting self-regulated learning in medical students: a qualitative study

    PubMed Central

    Jouhari, Zahra; Haghani, Fariba; Changiz, Tahereh

    2015-01-01

    Introduction Clinical courses are required of all medical students and means that they must develop the key skill of self-regulation during learning. The ability to self-regulate learning strategies is affected by different factors. This study determined the views of medical students on the factors affecting self-regulated learning (SRL). Method This study uses a qualitative approach and the content analysis method. Nineteen medical students in their fourth, fifth, and sixth years of study at Isfahan University of Medical Science participated in semi-structured, in-depth interviews. The students were selected using purposive sampling based on their overall grade point average (GPA). Results Five main themes were found to affect SRL. These themes included family with the two subthemes of family supervisory and supportive roles; peers with the two subthemes of facilitating and inhibiting roles; instructors with the two subthemes of personal and educational instructor's characteristics; educational environment with the two subthemes of facilitator and inhibitor roles; and student with the two subthemes of facilitating and inhibiting personal factors. Conclusion The outcomes of student understanding of the factors affecting self-regulation indicate that facilitating factors should be used on an individual basis to reduce the effect of inhibiting factors to improve self-regulation in students. PMID:26549046

  12. Everyday music listening and affect regulation: The role of MP3 players

    PubMed Central

    2013-01-01

    The use of digital portable music devices such as MP3 players has rapidly increased during the last decade, and the sheer availability of music offered by such players raises questions about their impact on listeners’ mental and physical health and well-being. This article explores MP3 player use as an everyday tactic for affect regulation, here understood as an individual's efforts to maintain or change the intensity or duration of a given affect. The ability to understand and regulate affects has significant health implications, and among the tactics relevant to such regulation, engagement with music has proven to be particularly successful. The material presented in this article is based on a qualitative interview study focused on MP3 player use as a medium for musical self-care. Because MP3 users can listen to whatever they want, whenever they want, and target their music in the interests of managing and regulating moods and emotions, the MP3 player represents a valuable and convenient technology of affect regulation. PMID:23930987

  13. Affective Robotics: Modelling and Testing Cultural Prototypes.

    PubMed

    A Wilson, Paul; Lewandowska-Tomaszczyk, Barbara

    2014-01-01

    If robots are to successfully interact with humans, they need to measure, quantify and respond to the emotions we produce. Similar to humans, the perceptual cue inputs to any modelling that allows this will be based on behavioural expression and body activity features that are prototypical of each emotion. However, the likely employment of such robots in different cultures necessitates the tuning of the emotion feature recognition system to the specific feature profiles present in these cultures. The amount of tuning depends on the relative convergence of the cross-cultural mappings between the emotion feature profiles of the cultures where the robots will be used. The GRID instrument and the cognitive corpus linguistics methodology were used in a contrastive study analysing a selection of behavioural expression and body activity features to compare the feature profiles of joy, sadness, fear and anger within and between Polish and British English. The intra-linguistic differences that were found in the profile of emotion features suggest that weightings based on this profile can be used in robotic modelling to create emotion-sensitive socially interacting robots. Our cross-cultural results further indicate that this profile of features needs to be tuned in robots to make them emotionally competent in different cultures. PMID:25484993

  14. The relationships between HIV stigma, emotional status, and emotional regulation among HIV-affected children in rural China

    PubMed Central

    Wei, Wei; Li, Xiaoming; Harrison, Sayward; Zhao, Junfeng; Zhao, Guoxiang

    2016-01-01

    ABSTRACT Children affected by HIV/AIDS have unique psychosocial needs that often go unaddressed in traditional treatment approaches. They are more likely than unaffected peers to encounter stigma, including overt discriminatory behaviors, as well as stereotyped attitudes. In addition, HIV-affected children are at risk for experiencing negative affect, including sadness and depression. Previous studies have identified a link between HIV stigma and the subsequent emotional status of children affected by HIV/AIDS. However, limited data are available regarding protective psychological factors that can mitigate the effects of HIV stigma and thus promote resiliency for this vulnerable population. Utilizing data from 790 children aged 6–17 years affected by parental HIV in rural central China this study aims to examine the association between HIV stigma, including both enacted and perceived stigma, and emotional status among HIV-affected children, as well as to evaluate the mediating effects of emotional regulation on the relationship between HIV stigma and emotional status. In addition, the moderating role of age is tested. Multiple regression was conducted to test the mediation model. We found that the experience of HIV stigma had a direct positive effect on negative emotions among children affected by HIV. Emotional regulation offers a level of protection, as it mediated the impact of HIV stigma on negative emotions. Moreover, age was found to moderate the relationship between perceived stigma and negative emotions. A significant interaction between perceived stigma and age suggested that negative emotions increase with age among those who perceived a higher level of stigmatization. Results suggest that children affected by HIV may benefit from interventions designed to enhance their capacity to regulate emotions and that health professionals should be aware of the link between stigma and negative emotion in childhood and adolescence and use the knowledge to inform

  15. Neurofeedback, Affect Regulation and Attachment: A Case Study and Analysis of Anti-Social Personality

    ERIC Educational Resources Information Center

    Fisher, Sebern F.

    2007-01-01

    This case study examines the effects of neurofeedback (EEG biofeedback) training on affect regulation in a fifty-five year-old man with a history marked by fear, rage, alcoholism, chronic unemployment and multiple failed treatments. He had been diagnosed with ADHD and attachment disorder and met criteria for anti-social personality disorder. The…

  16. The Changing Climate Toward Occupational Regulation: How Does It Affect Cosmetology Board Members?

    ERIC Educational Resources Information Center

    Shimberg, Benjamin

    This document contains two letters. The first letter, which might have been written by a cosmetology licensing board member to his mother, illustrates the changing climate toward occupational regulations and how it might affect the attitudes of a board member. The second letter, the mother's reply, attempts to put some of the changes into a…

  17. Maternal Socialization of Positive Affect: The Impact of Invalidation on Adolescent Emotion Regulation and Depressive Symptomatology

    ERIC Educational Resources Information Center

    Yap, Marie B. H.; Allen, Nicholas B.; Ladouceur, Cecile D.

    2008-01-01

    This study examined the relations among maternal socialization of positive affect (PA), adolescent emotion regulation (ER), and adolescent depressive symptoms. Two hundred early adolescents, 11-13 years old, provided self-reports of ER strategies and depressive symptomatology; their mothers provided self-reports of socialization responses to…

  18. Affective Self-Regulation Trajectories during Secondary School Predict Substance Use among Urban Minority Young Adults

    ERIC Educational Resources Information Center

    Griffin, Kenneth W.; Lowe, Sarah R.; Acevedo, Bianca P.; Botvin, Gilbert J.

    2015-01-01

    This study explored the relationship between trajectories of affective self-regulation skills during secondary school and young adult substance use in a large multiethnic, urban sample (N = 995). During secondary school, participants completed a measure of cognitive and behavioral skills used to control negative, unpleasant emotions or perceived…

  19. The Role of Depression and Negative Affect Regulation Expectancies in Tobacco Smoking among College Students

    ERIC Educational Resources Information Center

    Schleicher, Holly E.; Harris, Kari Jo; Catley, Delwyn; Nazir, Niaman

    2009-01-01

    Objective: Expectancies about nicotine's ability to alleviate negative mood states may play a role in the relationship between smoking and depression. The authors examined the role of negative affect regulation expectancies as a potential mediator of depression (history of depression and depressive symptoms) and smoking among college students.…

  20. Developing Connections for Affective Regulation: Age-Related Changes in Emotional Brain Connectivity

    ERIC Educational Resources Information Center

    Perlman, Susan B.; Pelphrey, Kevin A.

    2011-01-01

    The regulation of affective arousal is a critical aspect of children's social and cognitive development. However, few studies have examined the brain mechanisms involved in the development of this aspect of "hot" executive functioning. This process has been conceptualized as involving prefrontal control of the amygdala. Here, using functional…

  1. 25 CFR 547.2 - How do these regulations affect state jurisdiction?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false How do these regulations affect state jurisdiction? 547.2 Section 547.2 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR HUMAN SERVICES MINIMUM TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY OF CLASS II GAMES § 547.2 How do...

  2. 25 CFR 547.2 - How do these regulations affect state jurisdiction?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false How do these regulations affect state jurisdiction? 547.2 Section 547.2 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR HUMAN SERVICES MINIMUM TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY OF CLASS II GAMES § 547.2 How do...

  3. 25 CFR 547.2 - How do these regulations affect state jurisdiction?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false How do these regulations affect state jurisdiction? 547.2 Section 547.2 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR HUMAN SERVICES MINIMUM TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY OF CLASS II GAMES § 547.2 How do...

  4. 75 FR 33501 - Definitions for Regulations Affecting All Savings Associations; Money Market Deposit Accounts

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-14

    ... deposit accounts, including Money Market Deposit Accounts. \\1\\ 74 FR 25629. Prior to the FRB amendments... such an amendment ] they would be at a competitive disadvantage. \\3\\ 74 FR 47050 (September 15, 2009... Office of Thrift Supervision 12 CFR Part 561 RIN 1550-AC40 Definitions for Regulations Affecting...

  5. Developmental Regulation with Progressive Vision Loss: Use of Control Strategies and Affective Well-Being

    ERIC Educational Resources Information Center

    Schilling, Oliver K.; Wahl, Hans-Werner; Boerner, Kathrin; Horowitz, Amy; Reinhardt, Joann P.; Cimarolli, Verena R.; Brennan-Ing, Mark; Heckhausen, Jutta

    2016-01-01

    The present study addresses older adults' developmental regulation when faced with progressive and irreversible vision loss. We used the motivational theory of life span development as a conceptual framework and examined changes in older adults' striving for control over everyday goal achievement, and their association with affective well-being,…

  6. When death is not a problem: Regulating implicit negative affect under mortality salience.

    PubMed

    Lüdecke, Christina; Baumann, Nicola

    2015-12-01

    Terror management theory assumes that death arouses existential anxiety in humans which is suppressed in focal attention. Whereas most studies provide indirect evidence for negative affect under mortality salience by showing cultural worldview defenses and self-esteem strivings, there is only little direct evidence for implicit negative affect under mortality salience. In the present study, we assume that this implicit affective reaction towards death depends on people's ability to self-regulate negative affect as assessed by the personality dimension of action versus state orientation. Consistent with our expectations, action-oriented participants judged artificial words to express less negative affect under mortality salience compared to control conditions whereas state-oriented participants showed the reversed pattern. PMID:26335149

  7. Better, Stronger, Faster Self-Serving Judgment, Affect Regulation, and the Optimal Vigilance Hypothesis

    PubMed Central

    Roese, Neal J.; Olson, James M.

    2008-01-01

    Self-serving judgments, in which the self is viewed more favorably than other people, are ubiquitous. Their dynamic variation within individuals may be explained in terms of the regulation of affect. Self-serving judgments produce positive emotions, and threat increases self-serving judgments (a compensatory pattern that restores affect to a set point or baseline). Perceived mutability is a key moderator of these judgments; low mutability (i.e., the circumstance is closed to modification) triggers a cognitive response aimed at affect regulation, whereas high mutability (i.e., the circumstance is open to further modification) activates direct behavioral remediation. Threats often require immediate response, whereas positive events do not. Because of this brief temporal window, an active mechanism is needed to restore negative (but not positive) affective shifts back to a set point. Without this active reset, an earlier threat would make the individual less vigilant toward a new threat. Thus, when people are sad, they aim to return their mood to baseline, often via self-serving judgments. We argue that asymmetric homeostasis enables optimal vigilance, which establishes a coherent theoretical account of the role of self-serving judgments in affect regulation. PMID:18552989

  8. The 'too muchness' of excitement: sexuality in light of excess, attachment and affect regulation.

    PubMed

    Benjamin, Jessica; Atlas, Galit

    2015-02-01

    This paper brings together contemporary thinking about early attachment and affect regulation with our clinical and theoretical understanding of the problems of adult sexuality. In addition to recent theories of affect regulation and attachment, we incorporate Laplanche's idea of 'excess', which was an important transitional concept integrating real experience with fantasy in sexuality. We elaborate the idea of excess-- 'too-muchness' --to illuminate the early overwhelming of the psyche that affects the formation of sexuality. Linked to recent theoretical developments, this idea helps to grasp the relationship between sexual excitement and early affect regulation, showing how excitement becomes dangerous, thus impeding or distorting desire. The 'too-muchness' of excitement recalls the experience of being a stimulated, overwhelmed, unsoothed child and influences later inability to tolerate sexual arousal and the excitement affect. A clinical case illustrates this connection between attachment trauma, anxiety about sexuality, as well as shameful experiences of gender identity as an area of trauma. We emphasize the importance of working through the terrors and desires of the mother-baby relationship as they emerge in the transference-countertransference in order to develop the ability to hold excitement and stimulation without experiencing the too-much as the intolerable. This includes the working-through of ruptures related to overstimulation as well as the delicate balance of attention to fantasy and intersubjective work in the transference. PMID:25704459

  9. Leucine metabolism regulates TRI6 expression and affects deoxynivalenol production and virulence in Fusarium graminearum.

    PubMed

    Subramaniam, Rajagopal; Narayanan, Swara; Walkowiak, Sean; Wang, Li; Joshi, Manisha; Rocheleau, Hélène; Ouellet, Thérèse; Harris, Linda J

    2015-11-01

    TRI6 is a positive regulator of the trichothecene gene cluster and the production of trichothecene mycotoxins [deoxynivalenol (DON)] and acetylated forms such as 15-Acetyl-DON) in the cereal pathogen Fusarium graminearum. As a global transcriptional regulator, TRI6 expression is modulated by nitrogen-limiting conditions, sources of nitrogen and carbon, pH and light. However, the mechanism by which these diverse environmental factors affect TRI6 expression remains underexplored. In our effort to understand how nutrients affect TRI6 regulation, comparative digital expression profiling was performed with a wild-type F. graminearum and a Δtri6 mutant strain, grown in nutrient-rich conditions. Analysis showed that TRI6 negatively regulates genes of the branched-chain amino acid (BCAA) metabolic pathway. Feeding studies with deletion mutants of MCC, encoding methylcrotonyl-CoA-carboxylase, one of the key enzymes of leucine metabolism, showed that addition of leucine specifically down-regulated TRI6 expression and reduced 15-ADON accumulation. Constitutive expression of TRI6 in the Δmcc mutant strain restored 15-ADON production. A combination of cellophane breach assays and pathogenicity experiments on wheat demonstrated that disrupting the leucine metabolic pathway significantly reduced disease. These findings suggest a complex interaction between one of the primary metabolic pathways with a global regulator of mycotoxin biosynthesis and virulence in F. graminearum. PMID:26248604

  10. Emotion Regulation and Excess Weight: Impaired Affective Processing Characterized by Dysfunctional Insula Activation and Connectivity

    PubMed Central

    Mata, Fernanda; Martínez-Zalacaín, Ignacio; Cano, Marta; Contreras-Rodríguez, Oren; Fernández-Aranda, Fernando; Yucel, Murat; Soriano-Mas, Carles; Verdejo-García, Antonio

    2016-01-01

    Emotion-regulation strategies are understood to influence food intake. This study examined the neurophysiological underpinnings of negative emotion processing and emotion regulation in individuals with excess weight compared to normal-weight controls. Fifteen participants with excess-weight (body mass index >25) and sixteen normal-weight controls (body mass index 18–25) performed an emotion-regulation task during functional magnetic resonance imaging. Participants were exposed to 24 negative affective or neutral pictures that they were instructed to Observe (neutral pictures), Maintain (sustain the emotion elicited by negative pictures) or Regulate (down-regulate the emotion provoked by negative pictures through previously trained reappraisal techniques). When instructed to regulate negative emotions by means of cognitive reappraisal, participants with excess weight displayed persistently heightened activation in the right anterior insula. Decreased responsivity was also found in right anterior insula, the orbitofrontal cortex and cerebellum during negative emotion experience in participants with excess weight. Psycho-physiological interaction analyses showed that excess-weight participants had decreased negative functional coupling between the right anterior insula and the right dlPFC, and the bilateral dmPFC during cognitive reappraisal. Our findings support contentions that excess weight is linked to an abnormal pattern of neural activation and connectivity during the experience and regulation of negative emotions, with the insula playing a key role in these alterations. We posit that ineffective regulation of emotional states contributes to the acquisition and preservation of excess weight. PMID:27003840

  11. Thoracic Aortic Aneurysm (TAAD)-causing Mutation in Actin Affects Formin Regulation of Polymerization*

    PubMed Central

    Malloy, Lindsey E.; Wen, Kuo-Kuang; Pierick, Alyson R.; Wedemeyer, Elesa W.; Bergeron, Sarah E.; Vanderpool, Nicole D.; McKane, Melissa; Rubenstein, Peter A.; Bartlett, Heather L.

    2012-01-01

    More than 30 mutations in ACTA2, which encodes α-smooth muscle actin, have been identified to cause autosomal dominant thoracic aortic aneurysm and dissection. The mutation R256H is of particular interest because it also causes patent ductus arteriosus and moyamoya disease. R256H is one of the more prevalent mutations and, based on its molecular location near the strand-strand interface in the actin filament, may affect F-actin stability. To understand the molecular ramifications of the R256H mutation, we generated Saccharomyces cerevisiae yeast cells expressing only R256H yeast actin as a model system. These cells displayed abnormal cytoskeletal morphology and increased sensitivity to latrunculin A. After cable disassembly induced by transient exposure to latrunculin A, mutant cells were delayed in reestablishing the actin cytoskeleton. In vitro, mutant actin exhibited a higher than normal critical concentration and a delayed nucleation. Consequently, we investigated regulation of mutant actin by formin, a potent facilitator of nucleation and a protein needed for normal vascular smooth muscle cell development. Mutant actin polymerization was inhibited by the FH1-FH2 fragment of the yeast formin, Bni1. This fragment strongly capped the filament rather than facilitating polymerization. Interestingly, phalloidin or the presence of wild type actin reversed the strong capping behavior of Bni1. Together, the data suggest that the R256H actin mutation alters filament conformation resulting in filament instability and misregulation by formin. These biochemical effects may contribute to abnormal histology identified in diseased arterial samples from affected patients. PMID:22753406

  12. Thoracic aortic aneurysm (TAAD)-causing mutation in actin affects formin regulation of polymerization.

    PubMed

    Malloy, Lindsey E; Wen, Kuo-Kuang; Pierick, Alyson R; Wedemeyer, Elesa W; Bergeron, Sarah E; Vanderpool, Nicole D; McKane, Melissa; Rubenstein, Peter A; Bartlett, Heather L

    2012-08-17

    More than 30 mutations in ACTA2, which encodes α-smooth muscle actin, have been identified to cause autosomal dominant thoracic aortic aneurysm and dissection. The mutation R256H is of particular interest because it also causes patent ductus arteriosus and moyamoya disease. R256H is one of the more prevalent mutations and, based on its molecular location near the strand-strand interface in the actin filament, may affect F-actin stability. To understand the molecular ramifications of the R256H mutation, we generated Saccharomyces cerevisiae yeast cells expressing only R256H yeast actin as a model system. These cells displayed abnormal cytoskeletal morphology and increased sensitivity to latrunculin A. After cable disassembly induced by transient exposure to latrunculin A, mutant cells were delayed in reestablishing the actin cytoskeleton. In vitro, mutant actin exhibited a higher than normal critical concentration and a delayed nucleation. Consequently, we investigated regulation of mutant actin by formin, a potent facilitator of nucleation and a protein needed for normal vascular smooth muscle cell development. Mutant actin polymerization was inhibited by the FH1-FH2 fragment of the yeast formin, Bni1. This fragment strongly capped the filament rather than facilitating polymerization. Interestingly, phalloidin or the presence of wild type actin reversed the strong capping behavior of Bni1. Together, the data suggest that the R256H actin mutation alters filament conformation resulting in filament instability and misregulation by formin. These biochemical effects may contribute to abnormal histology identified in diseased arterial samples from affected patients. PMID:22753406

  13. Addiction Motivation Reformulated: An Affective Processing Model of Negative Reinforcement

    ERIC Educational Resources Information Center

    Baker, Timothy B.; Piper, Megan E.; McCarthy, Danielle E.; Majeskie, Matthew R.; Fiore, Michael C.

    2004-01-01

    This article offers a reformulation of the negative reinforcement model of drug addiction and proposes that the escape and avoidance of negative affect is the prepotent motive for addictive drug use. The authors posit that negative affect is the motivational core of the withdrawal syndrome and argue that, through repeated cycles of drug use and…

  14. A STRIPAK component Strip regulates neuronal morphogenesis by affecting microtubule stability

    PubMed Central

    Sakuma, Chisako; Okumura, Misako; Umehara, Tomoki; Miura, Masayuki; Chihara, Takahiro

    2015-01-01

    During neural development, regulation of microtubule stability is essential for proper morphogenesis of neurons. Recently, the striatin-interacting phosphatase and kinase (STRIPAK) complex was revealed to be involved in diverse cellular processes. However, there is little evidence that STRIPAK components regulate microtubule dynamics, especially in vivo. Here, we show that one of the core STRIPAK components, Strip, is required for microtubule organization during neuronal morphogenesis. Knockdown of Strip causes a decrease in the level of acetylated α-tubulin in Drosophila S2 cells, suggesting that Strip influences the stability of microtubules. We also found that Strip physically and genetically interacts with tubulin folding cofactor D (TBCD), an essential regulator of α- and β-tubulin heterodimers. Furthermore, we demonstrate the genetic interaction between strip and Down syndrome cell adhesion molecule (Dscam), a cell surface molecule that is known to work with TBCD. Thus, we propose that Strip regulates neuronal morphogenesis by affecting microtubule stability. PMID:26644129

  15. Dysfunctional affect regulation in borderline personality disorder and in somatoform disorder

    PubMed Central

    van Dijke, Annemiek

    2012-01-01

    Background Although affect dysregulation is considered a core component of borderline personality disorder (BPD) and somatoform disorders (SoD), remarkably little research has focused on the prevalence and nature of affect dysregulation in these disorders. Also, despite apparent similarities, little is known about how dysfunctional under- and overregulation of affect and positive and negative somatoform and psychoform dissociative experiences inter-relate. Prior studies suggest a clear relationship between early childhood psychological trauma and affect dysregulation, especially when the caretaker is emotionally, sexually, or physically abusing the child, but how these relate to under- and overregulation while differentiating for developmental epochs is not clear. Although an elevated risk of childhood trauma exposure or complex posttraumatic stress disorder (CPTSD) symptoms has been reported in BPD and SoD, trauma histories, dysfunctional affect regulation, dissociation, PTSD, and CPTSD were never assessed in unison in BPD and/or SoD. Method BPD and/or SoD diagnoses were confirmed or ruled out in 472 psychiatric inpatients using clinical interviews. Dysfunctional under- and overregulation of affect and somatoform and psychoform dissociation, childhood trauma-by-primary-caretaker (TPC), PTSD, and CPTSD were all measured using self reports. Results No disorder-specific form of dysfunctional affect regulation was found. Although both BPD and SoD can involve affect dysregulation and dissociation, there is a wide range of intensity of dysfunctional regulation phenomena in patients with these diagnoses. Evidence was found for the existence of three qualitatively different forms of experiencing states: inhibitory experiencing states (overregulation of affect and negative psychoform dissociation) most commonly found in SoD, excitatory experiencing states (underregulation of affect and positive psychoform dissociation) most commonly found in BPD, and combination of

  16. Escaping affect: how motivated emotion regulation creates insensitivity to mass suffering.

    PubMed

    Cameron, C Daryl; Payne, B Keith

    2011-01-01

    As the number of people in need of help increases, the degree of compassion people feel for them ironically tends to decrease. This phenomenon is termed the collapse of compassion. Some researchers have suggested that this effect happens because emotions are not triggered by aggregates. We provide evidence for an alternative account. People expect the needs of large groups to be potentially overwhelming, and, as a result, they engage in emotion regulation to prevent themselves from experiencing overwhelming levels of emotion. Because groups are more likely than individuals to elicit emotion regulation, people feel less for groups than for individuals. In Experiment 1, participants displayed the collapse of compassion only when they expected to be asked to donate money to the victims. This suggests that the effect is motivated by self-interest. Experiment 2 showed that the collapse of compassion emerged only for people who were skilled at emotion regulation. In Experiment 3, we manipulated emotion regulation. Participants who were told to down-regulate their emotions showed the collapse of compassion, but participants who were told to experience their emotions did not. We examined the time course of these effects using a dynamic rating to measure affective responses in real time. The time course data suggested that participants regulate emotion toward groups proactively, by preventing themselves from ever experiencing as much emotion toward groups as toward individuals. These findings provide initial evidence that motivated emotion regulation drives insensitivity to mass suffering. PMID:21219076

  17. Fronto-temporal alterations and affect regulation in methamphetamine dependence with and without a history of psychosis.

    PubMed

    Uhlmann, Anne; Fouche, Jean-Paul; Koen, Nastassja; Meintjes, Ernesta M; Wilson, Don; Stein, Dan J

    2016-02-28

    Methamphetamine (MA) has been shown to have neurotoxic effects associated with brain structure changes and schizophrenia-like psychotic symptoms. Although these abnormalities may in turn be related to cognitive impairment and increased aggression, their association with affect dysregulation is less well studied. We investigated cortical thickness and subcortical volumes in 21 participants with MA dependence, 19 patients with MA-associated psychosis (MAP), and 19 healthy controls. Participants' affect regulation abilities were assessed through self-report scales on emotion reactivity (ERS) and difficulties in emotion regulation (DERS) and correlated with differences in cortical thickness. MAP patients showed thinner cortices in the fusiform and inferior temporal gyrus (ITG), orbitofrontal (OFC) and inferior frontal gyrus (IFG), and insula, compared to the MA group. MAP also showed significantly lower hippocampal volumes relative to MA and CTRL. Both clinical groups showed impairment in affect regulation, but only in MAP was this dysfunction associated with thinner cortices in ITG, OFC and IFG. Our findings suggest significant differences in cortical thickness in MA dependence with and without psychosis. Lower fronto-temporal cortical thickness and smaller hippocampal volumes in MAP are consistent with neuroimaging findings in other psychotic disorders, supporting the notion of MAP being a useful model of psychosis. PMID:26792587

  18. Self-Regulation Programs for At-Risk Youth: Are Teachers Affected Too?

    ERIC Educational Resources Information Center

    Lichtinger, Einat; Leichtentritt, Judith

    2016-01-01

    This study examines changes experienced by teachers of youth at socioeconomic risk during and after conducting self-regulation programs with their students. Participants' self-reports were classified into 3 change models. Teachers in the 1st model reported changes in their interaction with the school, their role with the students, and their own…

  19. Regulating and facilitating: the role of emotional intelligence in maintaining and using positive affect for creativity.

    PubMed

    Parke, Michael R; Seo, Myeong-Gu; Sherf, Elad N

    2015-05-01

    Although past research has identified the effects of emotional intelligence on numerous employee outcomes, the relationship between emotional intelligence and creativity has not been well established. We draw upon affective information processing theory to explain how two facets of emotional intelligence-emotion regulation and emotion facilitation-shape employee creativity. Specifically, we propose that emotion regulation ability enables employees to maintain higher positive affect (PA) when faced with unique knowledge processing requirements, while emotion facilitation ability enables employees to use their PA to enhance their creativity. We find support for our hypotheses using a multimethod (ability test, experience sampling, survey) and multisource (archival, self-reported, supervisor-reported) research design of early career managers across a wide range of jobs. PMID:25528247

  20. Global Regulator MorA Affects Virulence-Associated Protease Secretion in Pseudomonas aeruginosa PAO1

    PubMed Central

    Ravichandran, Ayshwarya; Wong, Chui Ching; Swarup, Sanjay

    2015-01-01

    Bacterial invasion plays a critical role in the establishment of Pseudomonas aeruginosa infection and is aided by two major virulence factors – surface appendages and secreted proteases. The second messenger cyclic diguanylate (c-di-GMP) is known to affect bacterial attachment to surfaces, biofilm formation and related virulence phenomena. Here we report that MorA, a global regulator with GGDEF and EAL domains that was previously reported to affect virulence factors, negatively regulates protease secretion via the type II secretion system (T2SS) in P. aeruginosa PAO1. Infection assays with mutant strains carrying gene deletion and domain mutants show that host cell invasion is dependent on the active domain function of MorA. Further investigations suggest that the MorA-mediated c-di-GMP signaling affects protease secretion largely at a post-translational level. We thus report c-di-GMP second messenger system as a novel regulator of T2SS function in P. aeruginosa. Given that T2SS is a central and constitutive pump, and the secreted proteases are involved in interactions with the microbial surroundings, our data broadens the significance of c-di-GMP signaling in P. aeruginosa pathogenesis and ecological fitness. PMID:25894344

  1. Regulating telomere length from the inside out: the replication fork model

    PubMed Central

    2016-01-01

    Telomere length is regulated around an equilibrium set point. Telomeres shorten during replication and are lengthened by telomerase. Disruption of the length equilibrium leads to disease; thus, it is important to understand the mechanisms that regulate length at the molecular level. The prevailing protein-counting model for regulating telomerase access to elongate the telomere does not explain accumulating evidence of a role of DNA replication in telomere length regulation. Here I present an alternative model: the replication fork model that can explain how passage of a replication fork and regulation of origin firing affect telomere length. PMID:27401551

  2. Functional Connectivity of Pain-Mediated Affect Regulation in Borderline Personality Disorder

    PubMed Central

    Niedtfeld, Inga; Kirsch, Peter; Schulze, Lars; Herpertz, Sabine C.; Bohus, Martin; Schmahl, Christian

    2012-01-01

    Affective instability and self-injurious behavior are important features of Borderline Personality Disorder. Whereas affective instability may be caused by a pattern of limbic hyperreactivity paired with dysfunctional prefrontal regulation mechanisms, painful stimulation was found to reduce affective arousal at the neural level, possibly underlying the soothing effect of pain in BPD. We used psychophysiological interactions to analyze functional connectivity of (para-) limbic brain structures (i.e. amygdala, insula, anterior cingulate cortex) in Borderline Personality Disorder in response to painful stimulation. Therefore, we re-analyzed a dataset from 20 patients with Borderline Personality Disorder and 23 healthy controls who took part in an fMRI-task inducing negative (versus neutral) affect and subsequently applying heat pain (versus warmth perception). Results suggest an enhanced negative coupling between limbic as well as paralimbic regions and prefrontal regions, specifically with the medial and dorsolateral prefrontal cortex, when patients experienced pain in addition to emotional arousing pictures. When neutral pictures were combined with painful heat sensation, we found positive connectivity in Borderline Personality Disorder between (para-)limbic brain areas and parts of the basal ganglia (lentiform nucleus, putamen), as well areas involved in self-referential processing (precuneus and posterior cingulate). We found further evidence for alterations in the emotion regulation process in Borderline Personality Disorder, in the way that pain improves the inhibition of limbic activity by prefrontal areas. This study provides new insights in pain processing in BPD, including enhanced coupling of limbic structures and basal ganglia. PMID:22428013

  3. 45 CFR Appendix I to Part 617 - List of Age Distinctions Provided in Federal Statutes or Regulations Affecting Federal Financial...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Statutes or Regulations Affecting Federal Financial Assistance Administered by NSF I Appendix I to Part 617... NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM NSF Pt... Regulations Affecting Federal Financial Assistance Administered by NSF I. Section 6 of Pub. L. 94-86, 42...

  4. 45 CFR Appendix I to Part 617 - List of Age Distinctions Provided in Federal Statutes or Regulations Affecting Federal Financial...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Statutes or Regulations Affecting Federal Financial Assistance Administered by NSF I Appendix I to Part 617... NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM NSF Pt... Regulations Affecting Federal Financial Assistance Administered by NSF I. Section 6 of Pub. L. 94-86, 42...

  5. 45 CFR Appendix I to Part 617 - List of Age Distinctions Provided in Federal Statutes or Regulations Affecting Federal Financial...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Statutes or Regulations Affecting Federal Financial Assistance Administered by NSF I Appendix I to Part 617... NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM NSF Pt... Regulations Affecting Federal Financial Assistance Administered by NSF I. Section 6 of Pub. L. 94-86, 42...

  6. 45 CFR Appendix I to Part 617 - List of Age Distinctions Provided in Federal Statutes or Regulations Affecting Federal Financial...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Statutes or Regulations Affecting Federal Financial Assistance Administered by NSF I Appendix I to Part 617... NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM NSF Pt... Regulations Affecting Federal Financial Assistance Administered by NSF I. Section 6 of Pub. L. 94-86, 42...

  7. 25 CFR 542.4 - How do these regulations affect minimum internal control standards established in a Tribal-State...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false How do these regulations affect minimum internal control... COMMISSION, DEPARTMENT OF THE INTERIOR HUMAN SERVICES MINIMUM INTERNAL CONTROL STANDARDS § 542.4 How do these regulations affect minimum internal control standards established in a Tribal-State compact? (a) If there is...

  8. 45 CFR Appendix I to Part 617 - List of Age Distinctions Provided in Federal Statutes or Regulations Affecting Federal Financial...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Statutes or Regulations Affecting Federal Financial Assistance Administered by NSF I Appendix I to Part 617.... 617, App. I Appendix I to Part 617—List of Age Distinctions Provided in Federal Statutes or Regulations Affecting Federal Financial Assistance Administered by NSF I. Section 6 of Pub. L. 94-86, 42...

  9. Eccentric Exercise Activates Novel Transcriptional Regulation of Hypertrophic Signaling Pathways Not Affected by Hormone Changes

    PubMed Central

    MacNeil, Lauren G.; Melov, Simon; Hubbard, Alan E.; Baker, Steven K.; Tarnopolsky, Mark A.

    2010-01-01

    Unaccustomed eccentric exercise damages skeletal muscle tissue, activating mechanisms of recovery and remodeling that may be influenced by the female sex hormone 17β-estradiol (E2). Using high density oligonucleotide based microarrays, we screened for differences in mRNA expression caused by E2 and eccentric exercise. After random assignment to 8 days of either placebo (CON) or E2 (EXP), eighteen men performed 150 single-leg eccentric contractions. Muscle biopsies were collected at baseline (BL), following supplementation (PS), +3 hours (3H) and +48 hours (48H) after exercise. Serum E2 concentrations increased significantly with supplementation (P<0.001) but did not affect microarray results. Exercise led to early transcriptional changes in striated muscle activator of Rho signaling (STARS), Rho family GTPase 3 (RND3), mitogen activated protein kinase (MAPK) regulation and the downstream transcription factor FOS. Targeted RT-PCR analysis identified concurrent induction of negative regulators of calcineurin signaling RCAN (P<0.001) and HMOX1 (P = 0.009). Protein contents were elevated for RND3 at 3H (P = 0.02) and FOS at 48H (P<0.05). These findings indicate that early RhoA and NFAT signaling and regulation are altered following exercise for muscle remodeling and repair, but are not affected by E2. PMID:20502695

  10. [Containing, right hemisphere: projective identification as an interpersonal mechanism, the ability for affect regulation].

    PubMed

    Becker, Tobias; Streeck-Fischer, Annette

    2012-01-01

    The capacity of affect regulation develops with priority in reciprocal, non-verbal communication processes between the early caregiver and the baby. In this process, the projective identification plays the role of crucial means of communication. Processes of projective identification which emerge in therapeutic and educational interactions can be understood as such an early form of communication which contributes to the afterward-ripening of the capacity of affect regulation. Before the background of recent neuro-psychological findings it becomes clear, why the reciprocal and non-verbal communication between the early caregiver and infant as well as between the therapist and the patient is of such fundamental importance for the structural (re-) maturation of the right cerebral hemisphere, as well as for the connections between the left and right hemisphere. In case the projective identification persists as a defensive strategy in dealing with other people, pathological interaction circles can develop which can be overcome only when, for example, the other person assumes the role of the "regulating other". PMID:22957395

  11. Mathematical Modelling of Metabolic Regulation in Aging

    PubMed Central

    Mc Auley, Mark T.; Mooney, Kathleen M.; Angell, Peter J.; Wilkinson, Stephen J.

    2015-01-01

    The underlying cellular mechanisms that characterize aging are complex and multifaceted. However, it is emerging that aging could be regulated by two distinct metabolic hubs. These hubs are the pathway defined by the mammalian target of rapamycin (mTOR) and that defined by the NAD+-dependent deacetylase enzyme, SIRT1. Recent experimental evidence suggests that there is crosstalk between these two important pathways; however, the mechanisms underpinning their interaction(s) remains poorly understood. In this review, we propose using computational modelling in tandem with experimentation to delineate the mechanism(s). We briefly discuss the main modelling frameworks that could be used to disentangle this relationship and present a reduced reaction pathway that could be modelled. We conclude by outlining the limitations of computational modelling and by discussing opportunities for future progress in this area. PMID:25923415

  12. Mathematical modelling of metabolic regulation in aging.

    PubMed

    Auley, Mark T Mc; Mooney, Kathleen M; Angell, Peter J; Wilkinson, Stephen J

    2015-01-01

    The underlying cellular mechanisms that characterize aging are complex and multifaceted. However, it is emerging that aging could be regulated by two distinct metabolic hubs. These hubs are the pathway defined by the mammalian target of rapamycin (mTOR) and that defined by the NAD+-dependent deacetylase enzyme, SIRT1. Recent experimental evidence suggests that there is crosstalk between these two important pathways; however, the mechanisms underpinning their interaction(s) remains poorly understood. In this review, we propose using computational modelling in tandem with experimentation to delineate the mechanism(s). We briefly discuss the main modelling frameworks that could be used to disentangle this relationship and present a reduced reaction pathway that could be modelled. We conclude by outlining the limitations of computational modelling and by discussing opportunities for future progress in this area. PMID:25923415

  13. Incorporating affective bias in models of human decision making

    NASA Technical Reports Server (NTRS)

    Nygren, Thomas E.

    1991-01-01

    Research on human decision making has traditionally focused on how people actually make decisions, how good their decisions are, and how their decisions can be improved. Recent research suggests that this model is inadequate. Affective as well as cognitive components drive the way information about relevant outcomes and events is perceived, integrated, and used in the decision making process. The affective components include how the individual frames outcomes as good or bad, whether the individual anticipates regret in a decision situation, the affective mood state of the individual, and the psychological stress level anticipated or experienced in the decision situation. A focus of the current work has been to propose empirical studies that will attempt to examine in more detail the relationships between the latter two critical affective influences (mood state and stress) on decision making behavior.

  14. Affective regulation of stereotype activation: it's the (accessible) thought that counts.

    PubMed

    Huntsinger, Jeffrey R; Sinclair, Stacey; Dunn, Elizabeth; Clore, Gerald L

    2010-04-01

    Prior research has found that positive affect, compared to negative affect, increases stereotype activation. In four experiments the authors explore whether the link between affect and stereotype activation depends on the relative accessibility of stereotype-relevant thoughts and response tendencies. As well as manipulating mood, the authors measured or manipulated the accessibility of egalitarian response tendencies (Experiments 1 and 2) and counterstereotypic thoughts (Experiments 2 through 4). In the absence of such response tendencies and thoughts, people in positive moods displayed greater stereotype activation-consistent with past research. By contrast, in the presence of accessible egalitarian response tendencies or counterstereotypic thoughts, people in positive moods exhibited less stereotype activation than those in negative moods. Implications of these results for existing affect-cognition models are discussed. PMID:20363909

  15. Khat use and trait anger: effects on affect regulation during an acute stressful challenge.

    PubMed

    Bongard, Stephan; al'Absi, Mustafa; Khalil, Najat Sayem; Al Habori, Molham

    2011-01-01

    Khat (Catha edulis) is a widely used stimulating drug often consumed in daily routine in Yemen and East African countries. Chewing khat acutely elicits states of euphoria and feelings of well-being which later shift into emotional instability and low mood. Little is known about emotional regulation in habitual khat chewers. In this study, we compared self-reports on trait anger as well as positive and negative affect responses to a mental arithmetic challenge. Participants included 135 men and women from Yemen who chew khat regularly, occasionally or not at all. Participants attended a laboratory session that involved resting periods and performing a math challenge. Analyses of variance and regression show that regular khat chewing is associated with higher trait anger, more pronounced negative responses during stress and less pronounced positive emotional states. These results suggest that regular khat chewing is associated with disturbances in emotion regulation processes. PMID:21860244

  16. Studying Links between Hormones and Negative Affect: Models and Measures.

    ERIC Educational Resources Information Center

    Brooks-Gunn, Jeanne; And Others

    1994-01-01

    Considers eight models for the study of pubertal change that explore possible links between hormones and negative affective experiences, such as depression and aggression. Notes that hormonal effects, though small, have demonstrated stability and have interacted with psychological and social factors, implicating hormonal changes in the development…

  17. Cognitive, Affective, and Behavioral Determinants of Performance: A Process Model.

    ERIC Educational Resources Information Center

    Dorfman, Peter W.; Stephan, Walter G.

    Literature from organizational and social psychology has suggested that three types of factors influence performance, i.e., cognitive, affective and behavioral. A model was developed to test a set of propositions concerning the relationship between the three kinds of factors, and included attributions, expectancies, general emotional responses to…

  18. Epigenetic mechanisms affecting regulation of energy balance: many questions, few answers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Extensive human and animal model data show that nutrition and other environmental influences during critical periods of embryonic, fetal, and early postnatal life can affect the development of body weight regulatory pathways, with permanent consequences for risk of obesity. Epigenetic processes are ...

  19. Impact of physical maltreatment on the regulation of negative affect and aggression.

    PubMed

    Shackman, Jessica E; Pollak, Seth D

    2014-11-01

    Physically maltreated children are at risk for developing externalizing behavioral problems characterized by reactive aggression. The current experiment tested the relationships between individual differences in a neural index of social information processing, histories of child maltreatment, child negative affect, and aggressive behavior. Fifty boys (17 maltreated) performed an emotion recognition task while the P3b component of the event-related potential was recorded to index attention allocation to angry faces. Children then participated in a peer-directed aggression task. Negative affect was measured by recording facial electromyography, and aggression was indexed by the feedback that children provided to a putative peer. Physically maltreated children exhibited greater negative affect and more aggressive behavior, compared to nonmaltreated children, and this relationship was mediated by children's allocation of attention to angry faces. These data suggest that physical maltreatment leads to inappropriate regulation of both negative affect and aggression, which likely place maltreated children at increased risk for the development and maintenance of externalizing behavior disorders. PMID:24914736

  20. Impact of physical maltreatment on the regulation of negative affect and aggression

    PubMed Central

    SHACKMAN, JESSICA E.; POLLAK, SETH D.

    2015-01-01

    Physically maltreated children are at risk for developing externalizing behavioral problems characterized by reactive aggression. The current experiment tested the relationships between individual differences in a neural index of social information processing, histories of child maltreatment, child negative affect, and aggressive behavior. Fifty boys (17 maltreated) performed an emotion recognition task while the P3b component of the event-related potential was recorded to index attention allocation to angry faces. Children then participated in a peer-directed aggression task. Negative affect was measured by recording facial electromyography, and aggression was indexed by the feedback that children provided to a putative peer. Physically maltreated children exhibited greater negative affect and more aggressive behavior, compared to nonmaltreated children, and this relationship was mediated by children’s allocation of attention to angry faces. These data suggest that physical maltreatment leads to inappropriate regulation of both negative affect and aggression, which likely place maltreated children at increased risk for the development and maintenance of externalizing behavior disorders. PMID:24914736

  1. Variation in orbitofrontal cortex volume: relation to sex, emotion regulation and affect

    PubMed Central

    Welborn, B. Locke; Papademetris, Xenophon; Reis, Deidre L.; Rajeevan, Nallakkandi; Bloise, Suzanne M.

    2009-01-01

    Sex differences in brain structure have been examined extensively but are not completely understood, especially in relation to possible functional correlates. Our two aims in this study were to investigate sex differences in brain structure, and to investigate a possible relation between orbitofrontal cortex subregions and affective individual differences. We used tensor-based morphometry to estimate local brain volume from MPRAGE images in 117 healthy right-handed adults (58 female), age 18–40 years. We entered estimates of local brain volume as the dependent variable in a GLM, controlling for age, intelligence and whole-brain volume. Men had larger left planum temporale. Women had larger ventromedial prefrontal cortex (vmPFC), right lateral orbitofrontal (rlOFC), cerebellum, and bilateral basal ganglia and nearby white matter. vmPFC but not rlOFC volume covaried with self-reported emotion regulation strategies (reappraisal, suppression), expressivity of positive emotions (but not of negative), strength of emotional impulses, and cognitive but not somatic anxiety. vmPFC volume statistically mediated sex differences in emotion suppression. The results confirm prior reports of sex differences in orbitofrontal cortex structure, and are the first to show that normal variation in vmPFC volume is systematically related to emotion regulation and affective individual differences. PMID:20019072

  2. Emotion categorization using affective-pLSA model

    NASA Astrophysics Data System (ADS)

    Liu, Shuoyan; Xu, De; Feng, Songhe

    2010-12-01

    Emotion categorization of natural scene images represents a very useful task for automatic image analysis systems. Psychological experiments have shown that visual information at the emotion level is aggregated according to a set of rules. Hence, we attempt to discover the emotion descriptors based on the composition of visual word representation. First, the composition of visual word representation models each image as a matrix, where elements record the correlations of pairwise visual words. In this way, an image collection is modeled as a third-order tensor. Then we discover the emotion descriptors using a novel affective-probabilistic latent semantic analysis (affective-pLSA) model, which is an extension of the pLSA model, on this tensor representation. Considering that the natural scene image may evoke multiple emotional feelings, emotion categorization is carried out using the multilabel k-nearest-neighbor approach based on emotion descriptors. The proposed approach has been tested on the International Affective Picture System and a collection of social images from the Flickr website. The experimental results have demonstrated the effectiveness of the proposed method for eliciting image emotions.

  3. Emotion Risk-Factor in Patients With Cardiac Diseases: The Role of Cognitive Emotion Regulation Strategies, Positive Affect and Negative Affect (A Case-Control Study)

    PubMed Central

    Bahremand, Mostafa; Alikhani, Mostafa; Zakiei, Ali; Janjani, Parisa; Aghaei, Abbas

    2016-01-01

    Application of psychological interventions is essential in classic treatments for patient with cardiac diseases. The present study compared cognitive emotion regulation strategies, positive affect, and negative affect for cardiac patients with healthy subjects. This study was a case-control study. Fifty subjects were selected using convenient sampling method from cardiac (coronary artery disease) patients presenting in Imam Ali medical center of Kermanshah, Iran in the spring 2013. Fifty subjects accompanied the patients to the medical center, selected as control group, did not have any history of cardiac diseases. For collecting data, the cognitive emotion regulation questionnaire and positive and negative affect scales were used. For data analysis, multivariate analysis of variance (MANOVA) was applied using the SPSS statistical software (ver. 19.0). In all cognitive emotion regulation strategies, there was a significant difference between the two groups. A significant difference was also detected regarding positive affect between the two groups, but no significant difference was found regarding negative affect. We found as a result that, having poor emotion regulation strategies is a risk factor for developing heart diseases. PMID:26234976

  4. Emotion malleability beliefs, emotion regulation, and psychopathology: Integrating affective and clinical science.

    PubMed

    Kneeland, Elizabeth T; Dovidio, John F; Joormann, Jutta; Clark, Margaret S

    2016-04-01

    Beliefs that individuals hold about whether emotions are malleable or fixed, also referred to as emotion malleability beliefs, may play a crucial role in individuals' emotional experiences and their engagement in changing their emotions. The current review integrates affective science and clinical science perspectives to provide a comprehensive review of how emotion malleability beliefs relate to emotionality, emotion regulation, and specific clinical disorders and treatment. Specifically, we discuss how holding more malleable views of emotion could be associated with more active emotion regulation efforts, greater motivation to engage in active regulatory efforts, more effort expended regulating emotions, and lower levels of pathological distress. In addition, we explain how extending emotion malleability beliefs into the clinical domain can complement and extend current conceptualizations of major depressive disorder, social anxiety disorder, and generalized anxiety disorder. This may prove important given the increasingly central role emotion dysregulation has been given in conceptualization and intervention for these psychiatric conditions. Additionally, discussion focuses on how emotion beliefs could be more explicitly addressed in existing cognitive therapies. Promising future directions for research are identified throughout the review. PMID:27086086

  5. 7SK small nuclear RNA directly affects HMGA1 function in transcription regulation

    PubMed Central

    Eilebrecht, Sebastian; Brysbaert, Guillaume; Wegert, Thomas; Urlaub, Henning; Benecke, Bernd-Joachim; Benecke, Arndt

    2011-01-01

    Non-coding (nc) RNAs are increasingly recognized to play important regulatory roles in eukaryotic gene expression. The highly abundant and essential 7SK ncRNA has been shown to negatively regulate RNA Polymerase II transcription by inactivating the positive transcription elongation factor b (P-TEFb) in cellular and Tat-dependent HIV transcription. Here, we identify a more general, P-TEFb-independent role of 7SK RNA in directly affecting the function of the architectural transcription factor and chromatin regulator HMGA1. An important regulatory role of 7SK RNA in HMGA1-dependent cell differentiation and proliferation regulation is uncovered with the identification of over 1500 7SK-responsive HMGA1 target genes. Elevated HMGA1 expression is observed in nearly every type of cancer making the use of a 7SK substructure in the inhibition of HMGA1 activity, as pioneered here, potentially useful in therapy. The 7SK-HMGA1 interaction not only adds an essential facet to the comprehension of transcriptional plasticity at the coupling of initiation and elongation, but also might provide a molecular link between HIV reprogramming of cellular gene expression-associated oncogenesis. PMID:21087998

  6. Modeling regulated water utility investment incentives

    NASA Astrophysics Data System (ADS)

    Padula, S.; Harou, J. J.

    2014-12-01

    This work attempts to model the infrastructure investment choices of privatized water utilities subject to rate of return and price cap regulation. The goal is to understand how regulation influences water companies' investment decisions such as their desire to engage in transfers with neighbouring companies. We formulate a profit maximization capacity expansion model that finds the schedule of new supply, demand management and transfer schemes that maintain the annual supply-demand balance and maximize a companies' profit under the 2010-15 price control process in England. Regulatory incentives for costs savings are also represented in the model. These include: the CIS scheme for the capital expenditure (capex) and incentive allowance schemes for the operating expenditure (opex) . The profit-maximizing investment program (what to build, when and what size) is compared with the least cost program (social optimum). We apply this formulation to several water companies in South East England to model performance and sensitivity to water network particulars. Results show that if companies' are able to outperform the regulatory assumption on the cost of capital, a capital bias can be generated, due to the fact that the capital expenditure, contrarily to opex, can be remunerated through the companies' regulatory capital value (RCV). The occurrence of the 'capital bias' or its entity depends on the extent to which a company can finance its investments at a rate below the allowed cost of capital. The bias can be reduced by the regulatory penalties for underperformances on the capital expenditure (CIS scheme); Sensitivity analysis can be applied by varying the CIS penalty to see how and to which extent this impacts the capital bias effect. We show how regulatory changes could potentially be devised to partially remove the 'capital bias' effect. Solutions potentially include allowing for incentives on total expenditure rather than separately for capex and opex and allowing

  7. Modelling cognitive affective biases in major depressive disorder using rodents.

    PubMed

    Hales, Claire A; Stuart, Sarah A; Anderson, Michael H; Robinson, Emma S J

    2014-10-01

    Major depressive disorder (MDD) affects more than 10% of the population, although our understanding of the underlying aetiology of the disease and how antidepressant drugs act to remediate symptoms is limited. Major obstacles include the lack of availability of good animal models that replicate aspects of the phenotype and tests to assay depression-like behaviour in non-human species. To date, research in rodents has been dominated by two types of assays designed to test for depression-like behaviour: behavioural despair tests, such as the forced swim test, and measures of anhedonia, such as the sucrose preference test. These tests have shown relatively good predictive validity in terms of antidepressant efficacy, but have limited translational validity. Recent developments in clinical research have revealed that cognitive affective biases (CABs) are a key feature of MDD. Through the development of neuropsychological tests to provide objective measures of CAB in humans, we have the opportunity to use 'reverse translation' to develop and evaluate whether similar methods are suitable for research into MDD using animals. The first example of this approach was reported in 2004 where rodents in a putative negative affective state were shown to exhibit pessimistic choices in a judgement bias task. Subsequent work in both judgement bias tests and a novel affective bias task suggest that these types of assay may provide translational methods for studying MDD using animals. This review considers recent work in this area and the pharmacological and translational validity of these new animal models of CABs. PMID:24467454

  8. Cannabinoid Modulation of Frontolimbic Activation and Connectivity During Volitional Regulation of Negative Affect.

    PubMed

    Gorka, Stephanie M; Phan, K Luan; Lyons, Maryssa; Mori, Shoko; Angstadt, Mike; Rabinak, Christine A

    2016-06-01

    Behavioral and brain research indicates that administration of Δ(9)-tetrahydrocannabinol (THC) alters threat perception and enhances the suppression of conditioned fear responses via modulation of the frontolimbic circuit. No prior studies, however, have examined whether THC also affects volitional forms of emotion processing such as cognitive reappraisal. The aim of the current study was therefore to examine the effects of THC on frontolimbic activation and functional connectivity during cognitive reappraisal in a sample of healthy adults. The study was a randomized, double-blind, placebo-controlled, between-subject design and all participants ingested either an oral dose of synthetic THC (n=41) or placebo (n=37) before completion of an emotion regulation task during functional magnetic resonance imaging (fMRI). Functional connectivity was assessed using generalized psychophysiological interaction (gPPI) analyses. Results indicated that although there were no group differences in self-reported attenuation of negative affect during cognitive reappraisal, relative to placebo, THC increased amygdala activation and reduced amygdala and dorsolateral prefrontal cortex (dlPFC) functional coupling during cognitive reappraisal of emotionally negative pictures. This suggests that in addition to automatic emotional processes, THC affects frontolimbic functioning during cognitive reappraisal. PMID:26647971

  9. Integrating the Regulation of Affect, Behavior, and Cognition into Self-Regulated Learning Paradigms among Secondary and Post-Secondary Students

    ERIC Educational Resources Information Center

    Ben-Eliyahu, Adar; Linnenbrink-Garcia, Lisa

    2015-01-01

    An integrative framework for investigating self-regulated learning situated in students' favorite and least favorite courses was empirically tested in a sample of 178 high school and 280 college students. Building on cognitive, clinical, social, and educational conceptions of self-regulation, the current paper integrated affective (e.g.,…

  10. JMJD2A attenuation affects cell cycle and tumourigenic inflammatory gene regulation in lipopolysaccharide stimulated neuroectodermal stem cells.

    PubMed

    Das, Amitabh; Chai, Jin Choul; Jung, Kyoung Hwa; Das, Nando Dulal; Kang, Sung Chul; Lee, Young Seek; Seo, Hyemyung; Chai, Young Gyu

    2014-11-01

    JMJD2A is a lysine trimethyl-specific histone demethylase that is highly expressed in a variety of tumours. The role of JMJD2A in tumour progression remains unclear. The objectives of this study were to identify JMJD2A-regulated genes and understand the function of JMJD2A in p53-null neuroectodermal stem cells (p53(-/-) NE-4Cs). We determined the effect of LPS as a model of inflammation in p53(-/-) NE-4Cs and investigated whether the epigenetic modifier JMJD2A alter the expression of tumourigenic inflammatory genes. Global gene expression was measured in JMJD2A knockdown (kd) p53(-/-) NE-4Cs and in LPS-stimulated JMJD2A-kd p53(-/-) NE-4C cells. JMJD2A attenuation significantly down-regulated genes were Cdca2, Ccnd2, Ccnd1, Crebbp, IL6rα, and Stat3 related with cell cycle, proliferation, and inflammatory-disease responses. Importantly, some tumour-suppressor genes including Dapk3, Timp2 and TFPI were significantly up-regulated but were not affected by silencing of the JMJD2B. Furthermore, we confirmed the attenuation of JMJD2A also down-regulated Cdca2, Ccnd2, Crebbp, and Rest in primary NSCs isolated from the forebrains of E15 embryos of C57/BL6J mice with effective p53 inhibitor pifithrin-α (PFT-α). Transcription factor (TF) motif analysis revealed known binding patterns for CDC5, MYC, and CREB, as well as three novel motifs in JMJD2A-regulated genes. IPA established molecular networks. The molecular network signatures and functional gene-expression profiling data from this study warrants further investigation as an effective therapeutic target, and studies to elucidate the molecular mechanism of JMJD2A-kd-dependent effects in neuroectodermal stem cells should be performed. PMID:25193078

  11. Modeling Climate Change Effects on Stream Temperatures in Regulated Rivers

    NASA Astrophysics Data System (ADS)

    Null, S. E.; Akhbari, M.; Ligare, S. T.; Rheinheimer, D. E.; Peek, R.; Yarnell, S. M.; Viers, J. H.

    2013-12-01

    We provide a method for examining mesoscale stream temperature objectives downstream of dams with anticipated climate change using an integrated multi-model approach. Changing hydroclimatic conditions will likely impact stream temperatures within reservoirs and below dams, and affect downstream ecology. We model hydrology and water temperature using a series of linked models that includes a hydrology model to predict natural unimpaired flows in upstream reaches, a reservoir temperature simulation model , an operations model to simulate reservoir releases, and a stream temperature simulation model to simulate downstream conditions . All models are 1-dimensional and operate on either a weekly or daily timestep. First, we model reservoir thermal dynamics and release operations of hypothetical reservoirs of different sizes, elevations, and latitudes with climate-forced inflow hydrologies to examine the potential to manage stream temperatures for coldwater habitat. Results are presented as stream temperature change from the historical time period and indicate that reservoir releases are cooler than upstream conditions, although the absolute temperatures of reaches below dams warm with climate change. We also apply our method to a case study in California's Yuba River watershed to evaluate water regulation and hydropower operation effects on stream temperatures with climate change. Catchments of the upper Yuba River are highly-engineered, with multiple, interconnected infrastructure to provide hydropower, water supply, flood control, environmental flows, and recreation. Results illustrate climate-driven versus operations-driven changes to stream temperatures. This work highlights the need for methods to consider reservoir regulation effects on stream temperatures with climate change, particularly for hydropower relicensing (which currently ignores climate change) such that impacts to other beneficial uses like coldwater habitat and instream ecosystems can be

  12. Affective lability and difficulties with regulation are differentially associated with amygdala and prefrontal response in women with Borderline Personality Disorder.

    PubMed

    Silvers, Jennifer A; Hubbard, Alexa D; Biggs, Emily; Shu, Jocelyn; Fertuck, Eric; Chaudhury, Sadia; Grunebaum, Michael F; Weber, Jochen; Kober, Hedy; Chesin, Megan; Brodsky, Beth S; Koenigsberg, Harold; Ochsner, Kevin N; Stanley, Barbara

    2016-08-30

    The present neuroimaging study investigated two aspects of difficulties with emotion associated with Borderline Personality Disorder (BPD): affective lability and difficulty regulating emotion. While these two characteristics have been previously linked to BPD symptomology, it remains unknown whether individual differences in affective lability and emotion regulation difficulties are subserved by distinct neural substrates within a BPD sample. To address this issue, sixty women diagnosed with BPD were scanned while completing a task that assessed baseline emotional reactivity as well as top-down emotion regulation. More affective instability, as measured by the Affective Lability Scale (ALS), positively correlated with greater amygdala responses on trials assessing emotional reactivity. Greater difficulties with regulating emotion, as measured by the Difficulties with Emotion Regulation Scale (DERS), was negatively correlated with left Inferior Frontal Gyrus (IFG) recruitment on trials assessing regulatory ability. These findings suggest that, within a sample of individuals with BPD, greater bottom-up amygdala activity is associated with heightened affective lability. By contrast, difficulties with emotion regulation are related to reduced IFG recruitment during emotion regulation. These results point to distinct neural mechanisms for different aspects of BPD symptomology. PMID:27379614

  13. P. brasiliensis Virulence Is Affected by SconC, the Negative Regulator of Inorganic Sulfur Assimilation

    PubMed Central

    Menino, João Filipe; Saraiva, Margarida; Gomes-Rezende, Jéssica; Sturme, Mark; Pedrosa, Jorge; Castro, António Gil; Ludovico, Paula; Goldman, Gustavo H.; Rodrigues, Fernando

    2013-01-01

    Conidia/mycelium-to-yeast transition of Paracoccidioidesbrasiliensis is a critical step for the establishment of paracoccidioidomycosis, a systemic mycosis endemic in Latin America. Thus, knowledge of the factors that mediate this transition is of major importance for the design of intervention strategies. So far, the only known pre-requisites for the accomplishment of the morphological transition are the temperature shift to 37°C and the availability of organic sulfur compounds. In this study, we investigated the auxotrophic nature to organic sulfur of the yeast phase of Paracoccidioides, with special attention to P. brasiliensis species. For this, we addressed the role of SconCp, the negative regulator of the inorganic sulfur assimilation pathway, in the dimorphism and virulence of this pathogen. We show that down-regulation of SCONC allows initial steps of mycelium-to-yeast transition in the absence of organic sulfur compounds, contrarily to the wild-type fungus that cannot undergo mycelium-to-yeast transition under such conditions. However, SCONC down-regulated transformants were unable to sustain yeast growth using inorganic sulfur compounds only. Moreover, pulses with inorganic sulfur in SCONC down-regulated transformants triggered an increase of the inorganic sulfur metabolism, which culminated in a drastic reduction of the ATP and NADPH cellular levels and in higher oxidative stress. Importantly, the down-regulation of SCONC resulted in a decreased virulence of P. brasiliensis, as validated in an in vivo model of infection. Overall, our findings shed light on the inability of P. brasiliensis yeast to rely on inorganic sulfur compounds, correlating its metabolism with cellular energy and redox imbalances. Furthermore, the data herein presented reveal SconCp as a novel virulence determinant of P. brasiliensis. PMID:24066151

  14. Catching transcriptional regulation by thermostatistical modeling

    NASA Astrophysics Data System (ADS)

    Frank, Till D.; Cheong, Alex; Okada-Hatakeyama, Mariko; Kholodenko, Boris N.

    2012-08-01

    Gene expression is frequently regulated by multiple transcription factors (TFs). Thermostatistical methods allow for a quantitative description of interactions between TFs, RNA polymerase and DNA, and their impact on the transcription rates. We illustrate three different scales of the thermostatistical approach: the microscale of TF molecules, the mesoscale of promoter energy levels and the macroscale of transcriptionally active and inactive cells in a cell population. We demonstrate versatility of combinatorial transcriptional activation by exemplifying logic functions, such as AND and OR gates. We discuss a metric for cell-to-cell transcriptional activation variability known as Fermi entropy. Suitability of thermostatistical modeling is illustrated by describing the experimental data on transcriptional induction of NFκB and the c-Fos protein.

  15. Building Emotion and Affect Regulation (BEAR): Preliminary Evidence from an Open Trial in Children's Residential Group Homes in Singapore

    ERIC Educational Resources Information Center

    Pat-Horenczyk, R.; Shi, C. Sim Wei; Schramm-Yavin, S.; Bar-Halpern, M.; Tan, L. J.

    2015-01-01

    Background: The Building Emotion and Affect Regulation (BEAR) program is a theory-based group intervention for enhancing resilience in children, with a focus on strengthening emotion regulation. The BEAR is a 6-session protocol for children aged 7-12 who have been subject to traumatic life events. Objective: This paper presents the guiding…

  16. Does Training in How to Regulate One's Learning Affect How Students Report Self-Regulated Learning in Diary Tasks?

    ERIC Educational Resources Information Center

    Costa Ferreira, P.; Veiga Simão, A. M.; Lopes da Silva, A.

    2015-01-01

    The processes and perceptions of students' self-regulated learning are not easily measured. Thus, research has presented and suggested numerous ways in which these processes and perceptions of self-regulated learning can be investigated and assessed. Accordingly, this study aims to assess whether training in how to regulate one's learning is…

  17. Genetic diversity affects the strength of population regulation in a marine fish.

    PubMed

    Johnson, D W; Freiwald, J; Bernardi, G

    2016-03-01

    Variation is an essential feature of biological populations, yet much of ecological theory treats individuals as though they are identical. This simplifying assumption is often justified by the perception that variation among individuals does not have significant effects on the dynamics of whole populations. However, this perception may be skewed by a historic focus on studying single populations. A true evaluation of the extent to which among-individual variation affects the dynamics of populations requires the study of multiple populations. In this study, we examined variation in the dynamics of populations of a live-bearing, marine fish (black surfperch; Embiotoca jacksoni). In collaboration with an organization of citizen scientists (Reef Check California), we were able to examine the dynamics of eight populations that were distributed throughout approximately 700 km of coastline, a distance that encompasses much of this species' range. We hypothesized that genetic variation within a local population would be related to the intensity of competition and to the strength of population regulation. To test this hypothesis, we examined whether genetic diversity (measured by the diversity of mitochondrial DNA haplotypes) was related to the strength of population regulation. Low-diversity populations experienced strong density dependence in population growth rates and population sizes were regulated much more tightly than they were in high-diversity populations. Mechanisms that contributed to this pattern include links between genetic diversity, habitat use, and spatial crowding. On average, low-diversity populations used less of the available habitat and exhibited greater spatial clustering (and more intense competition) for a given level of density (measured at the scale of the reef). Although the populations we studied also varied with respect to exogenous characteristics (habitat complexity, densities of predators, and interspecific competitors), none of these

  18. Leading trends in environmental regulation that affect energy development. Final report

    SciTech Connect

    Steele, R V; Attaway, L D; Christerson, J A; Kikel, D A; Kuebler, J D; Lupatkin, B M; Liu, C S; Meyer, R; Peyton, T O; Sussin, M H

    1980-01-01

    Major environmental issues that are likely to affect the implementation of energy technologies between now and the year 2000 are identified and assessed. The energy technologies specifically addressed are: oil recovery and processing; gas recovery and processing; coal liquefaction; coal gasification (surface); in situ coal gasification; direct coal combustion; advanced power systems; magnetohydrodynamics; surface oil shale retorting; true and modified in situ oil shale retorting; geothermal energy; biomass energy conversion; and nuclear power (fission). Environmental analyses of these technologies included, in addition to the main processing steps, the complete fuel cycle from resource extraction to end use. A comprehensive survey of the environmental community (including environmental groups, researchers, and regulatory agencies) was carried out in parallel with an analysis of the technologies to identify important future environmental issues. Each of the final 20 issues selected by the project staff has the following common attributes: consensus of the environmental community that the issue is important; it is a likely candidate for future regulatory action; it deals with a major environmental aspect of energy development. The analyses of the 20 major issues address their environmental problem areas, current regulatory status, and the impact of future regulations. These analyses are followed by a quantitative assessment of the impact on energy costs and nationwide pollutant emissions of possible future regulations. This is accomplished by employing the Strategic Environmental Assessment System (SEAS) for a subset of the 20 major issues. The report concludes with a more general discussion of the impact of environmental regulatory action on energy development.

  19. Enhancer of Rudimentary Homolog Affects the Replication Stress Response through Regulation of RNA Processing

    PubMed Central

    Kavanaugh, Gina; Zhao, Runxiang; Guo, Yan; Mohni, Kareem N.; Glick, Gloria; Lacy, Monica E.; Hutson, M. Shane; Ascano, Manuel

    2015-01-01

    Accurate replication of DNA is imperative for the maintenance of genomic integrity. We identified Enhancer of Rudimentary Homolog (ERH) using a whole-genome RNA interference (RNAi) screen to discover novel proteins that function in the replication stress response. Here we report that ERH is important for DNA replication and recovery from replication stress. ATR pathway activity is diminished in ERH-deficient cells. The reduction in ATR signaling corresponds to a decrease in the expression of multiple ATR pathway genes, including ATR itself. ERH interacts with multiple RNA processing complexes, including splicing regulators. Furthermore, splicing of ATR transcripts is deficient in ERH-depleted cells. Transcriptome-wide analysis indicates that ERH depletion affects the levels of ∼1,500 transcripts, with DNA replication and repair genes being highly enriched among those with reduced expression. Splicing defects were evident in ∼750 protein-coding genes, which again were enriched for DNA metabolism genes. Thus, ERH regulation of RNA processing is needed to ensure faithful DNA replication and repair. PMID:26100022

  20. Isolation and characterization of an Escherichia coli mutant affected in the regulation of adenylate cyclase.

    PubMed Central

    Guidi-Rontani, C; Danchin, A; Ullmann, A

    1981-01-01

    A mutant, cyaR1, affecting regulation of adenylate cyclase expression or activity is described. It was obtained as a thermoresistant revertant of a strain harboring a thermosensitive transcription termination factor, rho (rho-15). This mutant failed to synthesize adenosine 3',5'-phosphate and exhibited a carbohydrate-negative phenotype. A secondary mutation at the crp locus (crpC) restored the ability of the mutant to synthesize adenosine 3',5'-phosphate, enabled the expression of catabolite-sensitive operons, and conferred on the strain an extreme sensitivity to catabolite repression. In addition, we showed that the crpC mutation restored the pleiotropic carbohydrate-positive phenotype even in a delta cya background. We interpret this to mean that the adenosine 3',5'-phosphate receptor protein regulates negatively either the activity or synthesis of adenylate cyclase and that the cyaR1 mutation is either in a regulatory protein or a regulatory site of adenylate cyclase. Images PMID:6273380

  1. [Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain].

    PubMed

    Respondek, Michalina; Buszman, Ewa

    2015-01-01

    Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC), which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells. PMID:27259217

  2. Advanced Glycation End-Products affect transcription factors regulating insulin gene expression

    SciTech Connect

    Puddu, A.; Storace, D.; Odetti, P.; Viviani, G.L.

    2010-04-23

    Advanced Glycation End-Products (AGEs) are generated by the covalent interaction of reducing sugars with proteins, lipids or nucleic acids. AGEs are implicated in diabetic complications and pancreatic {beta}-cell dysfunction. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T15 to high concentrations of AGEs leads to a significant decrease of insulin secretion and content. Insulin gene transcription is positively regulated by the beta cell specific transcription factor PDX-1 (Pancreatic and Duodenal Homeobox-1). On the contrary, the forkhead transcription factor FoxO1 inhibits PDX-1 gene transcription. Activity of FoxO1 is regulated by post-translational modifications: phosphorylation deactivates FoxO1, and acetylation prevents FoxO1 ubiquitination. In this work we investigated whether AGEs affect expression and subcellular localization of PDX-1 and FoxO1. HIT-T15 cells were cultured for 5 days in presence of AGEs. Cells were then lysed and processed for subcellular fractionation. We determined intracellular insulin content, then we assessed the expression and subcellular localization of PDX-1, FoxO1, phosphoFoxO1 and acetylFoxO1. As expected intracellular insulin content was lower in HIT-T15 cells cultured with AGEs. The results showed that AGEs decreased expression and nuclear localization of PDX-1, reduced phosphorylation of FoxO1, and increased expression and acetylation of FoxO1. These results suggest that AGEs decrease insulin content unbalancing transcription factors regulating insulin gene expression.

  3. Secretagogin affects insulin secretion in pancreatic β-cells by regulating actin dynamics and focal adhesion

    PubMed Central

    Yang, Seo-Yun; Lee, Jae-Jin; Lee, Jin-Hee; Lee, Kyungeun; Oh, Seung Hoon; Lim, Yu-Mi; Lee, Myung-Shik; Lee, Kong-Joo

    2016-01-01

    Secretagogin (SCGN), a Ca2+-binding protein having six EF-hands, is selectively expressed in pancreatic β-cells and neuroendocrine cells. Previous studies suggested that SCGN enhances insulin secretion by functioning as a Ca2+-sensor protein, but the underlying mechanism has not been elucidated. The present study explored the mechanism by which SCGN enhances glucose-induced insulin secretion in NIT-1 insulinoma cells. To determine whether SCGN influences the first or second phase of insulin secretion, we examined how SCGN affects the kinetics of insulin secretion in NIT-1 cells. We found that silencing SCGN suppressed the second phase of insulin secretion induced by glucose and H2O2, but not the first phase induced by KCl stimulation. Recruitment of insulin granules in the second phase of insulin secretion was significantly impaired by knocking down SCGN in NIT-1 cells. In addition, we found that SCGN interacts with the actin cytoskeleton in the plasma membrane and regulates actin remodelling in a glucose-dependent manner. Since actin dynamics are known to regulate focal adhesion, a critical step in the second phase of insulin secretion, we examined the effect of silencing SCGN on focal adhesion molecules, including FAK (focal adhesion kinase) and paxillin, and the cell survival molecules ERK1/2 (extracellular-signal-regulated kinase 1/2) and Akt. We found that glucose- and H2O2-induced activation of FAK, paxillin, ERK1/2 and Akt was significantly blocked by silencing SCGN. We conclude that SCGN controls glucose-stimulated insulin secretion and thus may be useful in the therapy of Type 2 diabetes. PMID:27095850

  4. Secretagogin affects insulin secretion in pancreatic β-cells by regulating actin dynamics and focal adhesion.

    PubMed

    Yang, Seo-Yun; Lee, Jae-Jin; Lee, Jin-Hee; Lee, Kyungeun; Oh, Seung Hoon; Lim, Yu-Mi; Lee, Myung-Shik; Lee, Kong-Joo

    2016-06-15

    Secretagogin (SCGN), a Ca(2+)-binding protein having six EF-hands, is selectively expressed in pancreatic β-cells and neuroendocrine cells. Previous studies suggested that SCGN enhances insulin secretion by functioning as a Ca(2+)-sensor protein, but the underlying mechanism has not been elucidated. The present study explored the mechanism by which SCGN enhances glucose-induced insulin secretion in NIT-1 insulinoma cells. To determine whether SCGN influences the first or second phase of insulin secretion, we examined how SCGN affects the kinetics of insulin secretion in NIT-1 cells. We found that silencing SCGN suppressed the second phase of insulin secretion induced by glucose and H2O2, but not the first phase induced by KCl stimulation. Recruitment of insulin granules in the second phase of insulin secretion was significantly impaired by knocking down SCGN in NIT-1 cells. In addition, we found that SCGN interacts with the actin cytoskeleton in the plasma membrane and regulates actin remodelling in a glucose-dependent manner. Since actin dynamics are known to regulate focal adhesion, a critical step in the second phase of insulin secretion, we examined the effect of silencing SCGN on focal adhesion molecules, including FAK (focal adhesion kinase) and paxillin, and the cell survival molecules ERK1/2 (extracellular-signal-regulated kinase 1/2) and Akt. We found that glucose- and H2O2-induced activation of FAK, paxillin, ERK1/2 and Akt was significantly blocked by silencing SCGN. We conclude that SCGN controls glucose-stimulated insulin secretion and thus may be useful in the therapy of Type 2 diabetes. PMID:27095850

  5. How does bias correction of RCM precipitation affect modelled runoff?

    NASA Astrophysics Data System (ADS)

    Teng, J.; Potter, N. J.; Chiew, F. H. S.; Zhang, L.; Vaze, J.; Evans, J. P.

    2014-09-01

    Many studies bias correct daily precipitation from climate models to match the observed precipitation statistics, and the bias corrected data are then used for various modelling applications. This paper presents a review of recent methods used to bias correct precipitation from regional climate models (RCMs). The paper then assesses four bias correction methods applied to the weather research and forecasting (WRF) model simulated precipitation, and the follow-on impact on modelled runoff for eight catchments in southeast Australia. Overall, the best results are produced by either quantile mapping or a newly proposed two-state gamma distribution mapping method. However, the difference between the tested methods is small in the modelling experiments here (and as reported in the literature), mainly because of the substantial corrections required and inconsistent errors over time (non-stationarity). The errors remaining in bias corrected precipitation are typically amplified in modelled runoff. The tested methods cannot overcome limitation of RCM in simulating precipitation sequence, which affects runoff generation. Results further show that whereas bias correction does not seem to alter change signals in precipitation means, it can introduce additional uncertainty to change signals in high precipitation amounts and, consequently, in runoff. Future climate change impact studies need to take this into account when deciding whether to use raw or bias corrected RCM results. Nevertheless, RCMs will continue to improve and will become increasingly useful for hydrological applications as the bias in RCM simulations reduces.

  6. Morphogenic regulator EFG1 affects the drug susceptibilities of pathogenic Candida albicans.

    PubMed

    Prasad, Tulika; Hameed, Saif; Manoharlal, Raman; Biswas, Sudipta; Mukhopadhyay, Chinmay K; Goswami, Shyamal K; Prasad, Rajendra

    2010-08-01

    This study shows that the morphogenic regulator EFG1 level affects the drug susceptibilities of Candida albicans when grown on solid growth media. The Deltaefg1 mutant showed sensitivity particularly to those drugs that target ergosterol or its metabolism. Efg1p disruption showed a gene-dosage effect on drug susceptibilities and resulted in enhanced susceptibility to drugs in the homozygous mutant as compared with the wild type, heterozygous and revertant strains. The enhanced sensitivity to drugs was independent of the status of ATP-binding cassette and MFS multidrug efflux pumps of C. albicans. The Deltaefg1 mutant displayed increased membrane fluidity that coincided with the downregulation of ERG11 and upregulation of OLE1 and ERG3, leading to enhanced passive diffusion of drugs. Interestingly, Deltaefg1 mutant cells displayed enhanced levels of endogenous ROS levels. Notably, the higher levels of ROS in the Deltaefg1 mutant could be reversed by the addition of antioxidants. However, the restoration of ROS levels did not reverse the drug sensitivities of the Deltaefg1 mutant. Taken together, we, for the first time, establish a new role to EFG1 in affecting the drug susceptibilities of C. albicans cells, independent of ROS and known drug efflux mechanisms. PMID:20491944

  7. Regulating Availability: How Access to Alcohol Affects Drinking and Problems in Youth and Adults

    PubMed Central

    Gruenewald, Paul J.

    2011-01-01

    Regulations on the availability of alcohol have been used to moderate alcohol problems in communities throughout the world for thousands of years. In the latter half of the 20th century, quantitative studies of the effects of these regulations on drinking and related problems began in earnest as public health practitioners began to recognize the full extent of the harmful consequences related to drinking. This article briefly outlines the history of this work over four areas, focusing on the minimum legal drinking age, the privatization of alcohol control systems, outlet densities, and hours and days of sale. Some historical background is provided to emphasize the theoretical and empirical roots of this work and to highlight the substantial progress that has been made in each area. In general, this assessment suggests that higher minimum legal drinking ages, greater monopoly controls over alcohol sales, lower outlet numbers and reduced outlet densities, and limited hours and days of sale can effectively reduce alcohol sales, use, and problems. There are, however, substantial gaps in the research literature and a near absence of the quantitative theoretical work needed to direct alcohol-control efforts. Local community responses to alcohol policies are complex and heterogeneous, sometimes reinforcing and sometimes mitigating the effects of availability regulations. Quantitative models of policy effects are essential to accelerate progress toward the formulation and testing of optimal control strategies for the reduction of alcohol problems. PMID:22330225

  8. The reservoir model: a differential equation model of psychological regulation.

    PubMed

    Deboeck, Pascal R; Bergeman, C S

    2013-06-01

    Differential equation models can be used to describe the relationships between the current state of a system of constructs (e.g., stress) and how those constructs are changing (e.g., based on variable-like experiences). The following article describes a differential equation model based on the concept of a reservoir. With a physical reservoir, such as one for water, the level of the liquid in the reservoir at any time depends on the contributions to the reservoir (inputs) and the amount of liquid removed from the reservoir (outputs). This reservoir model might be useful for constructs such as stress, where events might "add up" over time (e.g., life stressors, inputs), but individuals simultaneously take action to "blow off steam" (e.g., engage coping resources, outputs). The reservoir model can provide descriptive statistics of the inputs that contribute to the "height" (level) of a construct and a parameter that describes a person's ability to dissipate the construct. After discussing the model, we describe a method of fitting the model as a structural equation model using latent differential equation modeling and latent distribution modeling. A simulation study is presented to examine recovery of the input distribution and output parameter. The model is then applied to the daily self-reports of negative affect and stress from a sample of older adults from the Notre Dame Longitudinal Study on Aging. PMID:23527605

  9. Stability Affects of Artificial Viscosity in Detonation Modeling

    SciTech Connect

    Vitello, P; Souers, P C

    2002-06-03

    Accurate multi-dimensional modeling of detonation waves in solid HE materials is a difficult task. To treat applied problems which contain detonation waves one must consider reacting flow with a wide range of length-scales, non-linear equations of state (EOS), and material interfaces at which the detonation wave interacts with other materials. To be useful numerical models of detonation waves must be accurate, stable, and insensitive to details of the modeling such as the mesh spacing, and mesh aspect ratio for multi-dimensional simulations. Studies we have performed show that numerical simulations of detonation waves can be very sensitive to the form of the artificial viscosity term used. The artificial viscosity term is included in our ALE hydrocode to treat shock discontinuities. We show that a monotonic, second order artificial viscosity model derived from an approximate Riemann solver scheme can strongly damp unphysical oscillations in the detonation wave reaction zone, improving the detonation wave boundary wall interaction. These issues are demonstrated in 2D model simulations presented of the 'Bigplate' test. Results using LX-I 7 explosives are compared with numerical simulation results to demonstrate the affects of the artificial viscosity model.

  10. Regulation of Sulphur Assimilation Is Essential for Virulence and Affects Iron Homeostasis of the Human-Pathogenic Mould Aspergillus fumigatus

    PubMed Central

    Amich, Jorge; Schafferer, Lukas; Haas, Hubertus; Krappmann, Sven

    2013-01-01

    Sulphur is an essential element that all pathogens have to absorb from their surroundings in order to grow inside their infected host. Despite its importance, the relevance of sulphur assimilation in fungal virulence is largely unexplored. Here we report a role of the bZIP transcription factor MetR in sulphur assimilation and virulence of the human pathogen Aspergillus fumigatus. The MetR regulator is essential for growth on a variety of sulphur sources; remarkably, it is fundamental for assimilation of inorganic S-sources but dispensable for utilization of methionine. Accordingly, it strongly supports expression of genes directly related to inorganic sulphur assimilation but not of genes connected to methionine metabolism. On a broader scale, MetR orchestrates the comprehensive transcriptional adaptation to sulphur-starving conditions as demonstrated by digital gene expression analysis. Surprisingly, A. fumigatus is able to utilize volatile sulphur compounds produced by its methionine catabolism, a process that has not been described before and that is MetR-dependent. The A. fumigatus MetR transcriptional activator is important for virulence in both leukopenic mice and an alternative mini-host model of aspergillosis, as it was essential for the development of pulmonary aspergillosis and supported the systemic dissemination of the fungus. MetR action under sulphur-starving conditions is further required for proper iron regulation, which links regulation of sulphur metabolism to iron homeostasis and demonstrates an unprecedented regulatory crosstalk. Taken together, this study provides evidence that regulation of sulphur assimilation is not only crucial for A. fumigatus virulence but also affects the balance of iron in this prime opportunistic pathogen. PMID:24009505

  11. Global parameter estimation for thermodynamic models of transcriptional regulation.

    PubMed

    Suleimenov, Yerzhan; Ay, Ahmet; Samee, Md Abul Hassan; Dresch, Jacqueline M; Sinha, Saurabh; Arnosti, David N

    2013-07-15

    Deciphering the mechanisms involved in gene regulation holds the key to understanding the control of central biological processes, including human disease, population variation, and the evolution of morphological innovations. New experimental techniques including whole genome sequencing and transcriptome analysis have enabled comprehensive modeling approaches to study gene regulation. In many cases, it is useful to be able to assign biological significance to the inferred model parameters, but such interpretation should take into account features that affect these parameters, including model construction and sensitivity, the type of fitness calculation, and the effectiveness of parameter estimation. This last point is often neglected, as estimation methods are often selected for historical reasons or for computational ease. Here, we compare the performance of two parameter estimation techniques broadly representative of local and global approaches, namely, a quasi-Newton/Nelder-Mead simplex (QN/NMS) method and a covariance matrix adaptation-evolutionary strategy (CMA-ES) method. The estimation methods were applied to a set of thermodynamic models of gene transcription applied to regulatory elements active in the Drosophila embryo. Measuring overall fit, the global CMA-ES method performed significantly better than the local QN/NMS method on high quality data sets, but this difference was negligible on lower quality data sets with increased noise or on data sets simplified by stringent thresholding. Our results suggest that the choice of parameter estimation technique for evaluation of gene expression models depends both on quality of data, the nature of the models [again, remains to be established] and the aims of the modeling effort. PMID:23726942

  12. How processing digital elevation models can affect simulated water budgets

    USGS Publications Warehouse

    Kuniansky, E.L.; Lowery, M.A.; Campbell, B.G.

    2009-01-01

    For regional models, the shallow water table surface is often used as a source/sink boundary condition, as model grid scale precludes simulation of the water table aquifer. This approach is appropriate when the water table surface is relatively stationary. Since water table surface maps are not readily available, the elevation of the water table used in model cells is estimated via a two-step process. First, a regression equation is developed using existing land and water table elevations from wells in the area. This equation is then used to predict the water table surface for each model cell using land surface elevation available from digital elevation models (DEM). Two methods of processing DEM for estimating the land surface for each cell are commonly used (value nearest the cell centroid or mean value in the cell). This article demonstrates how these two methods of DEM processing can affect the simulated water budget. For the example presented, approximately 20% more total flow through the aquifer system is simulated if the centroid value rather than the mean value is used. This is due to the one-third greater average ground water gradients associated with the centroid value than the mean value. The results will vary depending on the particular model area topography and cell size. The use of the mean DEM value in each model cell will result in a more conservative water budget and is more appropriate because the model cell water table value should be representative of the entire cell area, not the centroid of the model cell.

  13. Influencing Children's Self-Efficacy and Self-Regulation of Reading and Writing through Modeling

    ERIC Educational Resources Information Center

    Schunk, Dale H.; Zimmerman, Barry J.

    2007-01-01

    According to Bandura's social cognitive theory, self-efficacy and self-regulation are key processes that affect students' learning and achievement. This article discusses students' reading and writing performances using Zimmerman's four-phase social cognitive model of the development of self-regulatory competence. Modeling is an effective means of…

  14. Neutral models as a way to evaluate the Sea Level Affecting Marshes Model (SLAMM)

    EPA Science Inventory

    A commonly used landscape model to simulate wetland change – the Sea Level Affecting Marshes Model(SLAMM) – has rarely been explicitly assessed for its prediction accuracy. Here, we evaluated this model using recently proposed neutral models – including the random constraint matc...

  15. Curcumin affects cell survival and cell volume regulation in human renal and intestinal cells

    PubMed Central

    Kössler, Sonja; Nofziger, Charity; Jakab, Martin; Dossena, Silvia; Paulmichl, Markus

    2012-01-01

    Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1E,6E-heptadiene-3,5-dione or diferuloyl methane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. This substance has been used extensively in Ayurvedic medicine for centuries for its anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer properties linked to its pro-apoptotic and anti-proliferative actions. The underlying mechanisms of these diverse effects are complex, not fully elucidated and subject of intense scientific debate. Despite increasing evidence indicating that different cation channels can be a molecular target for curcumin, very little is known about the effect of curcumin on chloride channels. Since, (i) the molecular structure of curcumin indicates that the substance could potentially interact with chloride channels, (ii) chloride channels play a role during the apoptotic process and regulation of the cell volume, and (iii) apoptosis is a well known effect of curcumin, we set out to investigate whether or not curcumin could (i) exert a modulatory effect (direct or indirect) on the swelling activated chloride current IClswell in a human cell system, therefore (ii) affect cell volume regulation and (iii) ultimately modulate cell survival. The IClswell channels, which are essential for regulating the cell volume after swelling, are also known to be activated under isotonic conditions as an early event in the apoptotic process. Here we show that long-term exposure of a human kidney cell line to extracellular 0.1–10 μM curcumin modulates IClswell in a dose-dependent manner (0.1 μM curcumin is ineffective, 0.5–5.0 μM curcumin increase, while 10 μM curcumin decrease the current), and short-term exposure to micromolar concentrations of curcumin does not affect IClswell neither if applied from the extracellular nor from the intracellular side – therefore, a direct effect of curcumin on

  16. JMJD2A attenuation affects cell cycle and tumourigenic inflammatory gene regulation in lipopolysaccharide stimulated neuroectodermal stem cells

    SciTech Connect

    Das, Amitabh; Chai, Jin Choul; Jung, Kyoung Hwa; Das, Nando Dulal; Kang, Sung Chul; Lee, Young Seek; Seo, Hyemyung; Chai, Young Gyu

    2014-11-01

    JMJD2A is a lysine trimethyl-specific histone demethylase that is highly expressed in a variety of tumours. The role of JMJD2A in tumour progression remains unclear. The objectives of this study were to identify JMJD2A-regulated genes and understand the function of JMJD2A in p53-null neuroectodermal stem cells (p53{sup −/−} NE-4Cs). We determined the effect of LPS as a model of inflammation in p53{sup −/−} NE-4Cs and investigated whether the epigenetic modifier JMJD2A alter the expression of tumourigenic inflammatory genes. Global gene expression was measured in JMJD2A knockdown (kd) p53{sup −/−} NE-4Cs and in LPS-stimulated JMJD2A-kd p53{sup −/−} NE-4C cells. JMJD2A attenuation significantly down-regulated genes were Cdca2, Ccnd2, Ccnd1, Crebbp, IL6rα, and Stat3 related with cell cycle, proliferation, and inflammatory-disease responses. Importantly, some tumour-suppressor genes including Dapk3, Timp2 and TFPI were significantly up-regulated but were not affected by silencing of the JMJD2B. Furthermore, we confirmed the attenuation of JMJD2A also down-regulated Cdca2, Ccnd2, Crebbp, and Rest in primary NSCs isolated from the forebrains of E15 embryos of C57/BL6J mice with effective p53 inhibitor pifithrin-α (PFT-α). Transcription factor (TF) motif analysis revealed known binding patterns for CDC5, MYC, and CREB, as well as three novel motifs in JMJD2A-regulated genes. IPA established molecular networks. The molecular network signatures and functional gene-expression profiling data from this study warrants further investigation as an effective therapeutic target, and studies to elucidate the molecular mechanism of JMJD2A-kd-dependent effects in neuroectodermal stem cells should be performed. - Highlights: • Significant up-regulation of epigenetic modifier JMJD2A mRNA upon LPS treatment. • Inhibition of JMJD2A attenuated key inflammatory and tumourigenic genes. • Establishing IPA based functional genomics in JMJD2A-attenuated p53{sup

  17. A Pleiotropic Regulator, Frp, Affects Exopolysaccharide Synthesis, Biofilm Formation, and Competence Development in Streptococcus mutans

    PubMed Central

    Wang, Bing; Kuramitsu, Howard K.

    2006-01-01

    Exopolysaccharide synthesis, biofilm formation, and competence are important physiologic functions and virulence factors for Streptococcus mutans. In this study, we report the role of Frp, a transcriptional regulator, on the regulation of these traits crucial to pathogenesis. An Frp-deficient mutant showed decreased transcription of several genes important in virulence, including those encoding fructosyltransferase (Ftf), glucosyltransferase B (GtfB), and GtfC, by reverse transcription and quantitative real-time PCR. Expression of Ftf was decreased in the frp mutant, as assessed by Western blotting as well as by the activity assays. Frp deficiency also inhibited the production of GtfB in the presence of glucose and sucrose as well as the production of GtfC in the presence of glucose. As a consequence of the effects on GtfB and -C, sucrose-induced biofilm formation was decreased in the frp mutant. The expression of competence mediated by the competence-signaling peptide (CSP) system, as assessed by comC gene transcription, was attenuated in the frp mutant. As a result, the transformation efficiency was decreased in the frp mutant but was partially restored by adding synthetic CSP. Transcription of the frp gene was significantly increased in the frp mutant under all conditions tested, indicating that frp transcription is autoregulated. Furthermore, complementation of the frp gene in the frp mutant restored transcription of the affected genes to levels similar to those in the wild-type strain. These results suggest that Frp is a novel pleiotropic effector of multiple cellular functions and is involved in the modulation of exopolysaccharide synthesis, sucrose-dependent biofilm formation, and competence development. PMID:16861645

  18. A silent exonic SNP in kdm3a affects nucleic acids structure but does not regulate experimental autoimmune encephalomyelitis.

    PubMed

    Gillett, Alan; Bergman, Petra; Parsa, Roham; Bremges, Andreas; Giegerich, Robert; Jagodic, Maja

    2013-01-01

    Defining genetic variants that predispose for diseases is an important initiative that can improve biological understanding and focus therapeutic development. Genetic mapping in humans and animal models has defined genomic regions controlling a variety of phenotypes known as quantitative trait loci (QTL). Causative disease determinants, including single nucleotide polymorphisms (SNPs), lie within these regions and can often be identified through effects on gene expression. We previously identified a QTL on rat chromosome 4 regulating macrophage phenotypes and immune-mediated diseases including experimental autoimmune encephalomyelitis (EAE). Gene analysis and a literature search identified lysine-specific demethylase 3A (Kdm3a) as a potential regulator of these phenotypes. Genomic sequencing determined only two synonymous SNPs in Kdm3a. The silent synonymous SNP in exon 15 of Kdm3a caused problems with quantitative PCR detection in the susceptible strain through reduced amplification efficiency due to altered secondary cDNA structure. Shape Probability Shift analysis predicted that the SNP often affects RNA folding; thus, it may impact protein translation. Despite these differences in rats, genetic knockout of Kdm3a in mice resulted in no dramatic effect on immune system development and activation or EAE susceptibility and severity. These results provide support for tools that analyze causative SNPs that impact nucleic acid structures. PMID:24312603

  19. Pharmacologic regulation of AMPK in breast cancer affects cytoskeletal properties involved with microtentacle formation and re-attachment

    PubMed Central

    Chakrabarti, Kristi R.; Whipple, Rebecca A.; Boggs, Amanda E.; Hessler, Lindsay K.; Bhandary, Lekhana; Vitolo, Michele I.; Thompson, Keyata; Martin, Stuart S.

    2015-01-01

    The presence of tumor cells in the circulation is associated with a higher risk of metastasis in patients with breast cancer. Circulating breast tumor cells use tubulin-based structures known as microtentacles (McTNs) to re-attach to endothelial cells and arrest in distant organs. McTN formation is dependent on the opposing cytoskeletal forces of stable microtubules and the actin network. AMP-activated protein kinase (AMPK) is a cellular metabolic regulator that can alter actin and microtubule organization in epithelial cells. We report that AMPK can regulate the cytoskeleton of breast cancer cells in both attached and suspended conditions. We tested the effects of AMPK on microtubule stability and the actin-severing protein, cofilin. AMPK inhibition with compound c increased both microtubule stability and cofilin activation, which also resulted in higher McTN formation and re-attachment. Conversely, AMPK activation with A-769662 decreased microtubule stability and cofilin activation with concurrent decreases in McTN formation and cell re-attachment. This data shows for the first time that AMPK shifts the balance of cytoskeletal forces in suspended breast cancer cells, which affect their ability to form McTNs and re-attach. These results support a model where AMPK activators may be used therapeutically to reduce the metastatic efficiency of breast tumor cells. PMID:26431377

  20. Copy number variants in patients with intellectual disability affect the regulation of ARX transcription factor gene.

    PubMed

    Ishibashi, Minaka; Manning, Elizabeth; Shoubridge, Cheryl; Krecsmarik, Monika; Hawkins, Thomas A; Giacomotto, Jean; Zhao, Ting; Mueller, Thomas; Bader, Patricia I; Cheung, Sau W; Stankiewicz, Pawel; Bain, Nicole L; Hackett, Anna; Reddy, Chilamakuri C S; Mechaly, Alejandro S; Peers, Bernard; Wilson, Stephen W; Lenhard, Boris; Bally-Cuif, Laure; Gecz, Jozef; Becker, Thomas S; Rinkwitz, Silke

    2015-11-01

    Protein-coding mutations in the transcription factor-encoding gene ARX cause various forms of intellectual disability (ID) and epilepsy. In contrast, variations in surrounding non-coding sequences are correlated with milder forms of non-syndromic ID and autism and had suggested the importance of ARX gene regulation in the etiology of these disorders. We compile data on several novel and some already identified patients with or without ID that carry duplications of ARX genomic region and consider likely genetic mechanisms underlying the neurodevelopmental defects. We establish the long-range regulatory domain of ARX and identify its brain region-specific autoregulation. We conclude that neurodevelopmental disturbances in the patients may not simply arise from increased dosage due to ARX duplication. This is further exemplified by a small duplication involving a non-functional ARX copy, but with duplicated enhancers. ARX enhancers are located within a 504-kb region and regulate expression specifically in the forebrain in developing and adult zebrafish. Transgenic enhancer-reporter lines were used as in vivo tools to delineate a brain region-specific negative and positive autoregulation of ARX. We find autorepression of ARX in the telencephalon and autoactivation in the ventral thalamus. Fluorescently labeled brain regions in the transgenic lines facilitated the identification of neuronal outgrowth and pathfinding disturbances in the ventral thalamus and telencephalon that occur when arxa dosage is diminished. In summary, we have established a model for how breakpoints in long-range gene regulation alter the expression levels of a target gene brain region-specifically, and how this can cause subtle neuronal phenotypes relating to the etiology of associated neuropsychiatric disease. PMID:26337422

  1. Glucocorticoids increase adipocytes in muscle by affecting IL-4 regulated FAP activity

    PubMed Central

    Dong, Yanjun; Silva, Kleiton Augusto Santos; Dong, Yanlan; Zhang, Liping

    2014-01-01

    An increase in intramuscular adipocyte tissue (IMAT) is associated with glucose dysregulation, decreased muscle strength, and increased risk of disability. Unfortunately, the mechanisms stimulating intramuscular adipogenesis remain unclear. We found that dexamethasone (Dex) administration to mice with injured muscles stimulates the accumulation of IMAT. To identify precursors of these adipocytes, we isolated satellite cells and fibro/adipogenic progenitors (FAPs) from muscle; satellite cells did not differentiate into adipocytes even following Dex treatment. In contrast, Dex stimulated FAP differentiation into adipocytes. In vivo, we transplanted purified FAPs from transgenic, EGFP mice into the injured muscles of C57/BL6 mice and found that Dex administration stimulated adipogenesis from FAP-EGFP. The increase in adipogenesis depended on Dex-induced inhibition of interleukin-4 (IL-4). In the injured muscle of IL-4-knockout mice, the levels of adipocytes were increased, while in the injured muscles of Dex-treated mice with IL-4 injections, adipogenesis was suppressed. In cultured FAPs, IL-4 inhibited Dex-induced conversion of FAPs into adipocytes; this did not occur in FAPs expressing knockdown of the IL-4 receptor. Thus, we concluded that glucocorticoids stimulate FAPs to differentiate into adipocytes in injured muscles. This process is blocked by IL-4, suggesting that interfering with IL-4 signaling could prevent adipogenesis in muscle.—Dong, Y., Silva, K. A. S., Dong, Y., Zhang, L. Glucocorticoids increase adipocytes in muscle by affecting IL-4 regulated FAP activity. PMID:24948596

  2. Zinc oxide nanoparticles cause inhibition of microbial denitrification by affecting transcriptional regulation and enzyme activity.

    PubMed

    Zheng, Xiong; Su, Yinglong; Chen, Yinguang; Wan, Rui; Liu, Kun; Li, Mu; Yin, Daqiang

    2014-12-01

    Over the past few decades, human activities have accelerated the rates and extents of water eutrophication and global warming through increasing delivery of biologically available nitrogen such as nitrate and large emissions of anthropogenic greenhouse gases. In particular, nitrous oxide (N2O) is one of the most important greenhouse gases, because it has a 300-fold higher global warming potential than carbon dioxide. Microbial denitrification is a major pathway responsible for nitrate removal, and also a dominant source of N2O emissions from terrestrial or aquatic environments. However, whether the release of zinc oxide nanoparticles (ZnO NPs) into the environment affects microbial denitrification is largely unknown. Here we show that the presence of ZnO NPs lead to great increases in nitrate delivery (9.8-fold higher) and N2O emissions (350- and 174-fold higher in the gas and liquid phases, respectively). Our data further reveal that ZnO NPs significantly change the transcriptional regulations of glycolysis and polyhydroxybutyrate synthesis, which causes the decrease in reducing powers available for the reduction of nitrate and N2O. Moreover, ZnO NPs substantially inhibit the gene expressions and catalytic activities of key denitrifying enzymes. These negative effects of ZnO NPs on microbial denitrification finally cause lower nitrate removal and higher N2O emissions, which is likely to exacerbate water eutrophication and global warming. PMID:25384038

  3. Global proteomic analysis of protein acetylation affecting metabolic regulation in Daphnia pulex.

    PubMed

    Kwon, Oh Kwang; Sim, Juhee; Kim, Sun Ju; Oh, Hye Ryeung; Nam, Doo Hyun; Lee, Sangkyu

    2016-02-01

    Daphnia (Daphnia pulex) is a small planktonic crustacean and a key constituent of aquatic ecosystems. It is generally used as a model organism to study environmental toxic problems. In the past decade, genomic and proteomic datasets of Daphnia have been developed. The proteomic dataset allows for the investigation of toxicological effects in the context of "Daphnia proteomics," resulting in greater insights for toxicological research. To exploit Daphnia for ecotoxicological research, information on the post-translational modification (PTM) of proteins is necessary, as this is a critical regulator of biological processes. Acetylation of lysine (Kac) is a reversible and highly regulated PTM that is associated with diverse biological functions. However, a comprehensive description of Kac in Daphnia is not yet available. To understand the cellular distribution of lysine acetylation in Daphnia, we identified 98 acetylation sites in 65 proteins by immunoprecipitation using an anti-acetyllysine antibody and a liquid chromatography system supported by mass spectroscopy. We identified 28 acetylated sites related to metabolic proteins and six acetylated enzymes associated with the TCA cycle in Daphnia. From GO and KEGG enrichment analyses, we showed that Kac in D. pulex is highly enriched in proteins associated with metabolic processes. Our data provide the first global analysis of Kac in D. pulex and is an important resource for the functional analysis of Kac in this organism. PMID:26700148

  4. Xrn1/Pacman affects apoptosis and regulates expression of hid and reaper

    PubMed Central

    Waldron, Joseph A.; Jones, Christopher I.; Towler, Benjamin P.; Pashler, Amy L.; Grima, Dominic P.; Hebbes, Stephen; Crossman, Samuel H.; Zabolotskaya, Maria V.; Newbury, Sarah F.

    2015-01-01

    Programmed cell death, or apoptosis, is a highly conserved cellular process that is crucial for tissue homeostasis under normal development as well as environmental stress. Misregulation of apoptosis is linked to many developmental defects and diseases such as tumour formation, autoimmune diseases and neurological disorders. In this paper, we show a novel role for the exoribonuclease Pacman/Xrn1 in regulating apoptosis. Using Drosophila wing imaginal discs as a model system, we demonstrate that a null mutation in pacman results in small imaginal discs as well as lethality during pupation. Mutant wing discs show an increase in the number of cells undergoing apoptosis, especially in the wing pouch area. Compensatory proliferation also occurs in these mutant discs, but this is insufficient to compensate for the concurrent increase in apoptosis. The phenotypic effects of the pacman null mutation are rescued by a deletion that removes one copy of each of the pro-apoptotic genes reaper, hid and grim, demonstrating that pacman acts through this pathway. The null pacman mutation also results in a significant increase in the expression of the pro-apoptotic mRNAs, hid and reaper, with this increase mostly occurring at the post-transcriptional level, suggesting that Pacman normally targets these mRNAs for degradation. Our results uncover a novel function for the conserved exoribonuclease Pacman and suggest that this exoribonuclease is important in the regulation of apoptosis in other organisms. PMID:25836675

  5. Is attention to feelings beneficial or detrimental to affective well-being? Mood regulation as a moderator variable.

    PubMed

    Lischetzke, Tanja; Eid, Michael

    2003-12-01

    This research examined the functionality of attention to feelings for affective well-being. The authors found that mood regulation, but not clarity of feelings, moderated the attention-well-being relationship. For individuals with high mood regulation scores, attention was beneficial to affective well-being, whereas for individuals with low mood regulation scores, attention was detrimental to affective well-being. This finding was corroborated by self- and peer reports in Study 1 and replicated in Study 2. The validity of the scales was established by the convergence of self- and peer ratings. Moreover, Study 2 showed that dysfunctional and functional and self consciousness scales suppressed variance in attention to feelings, thereby revealing that attention incorporates both adaptive and maladaptive aspects. PMID:14674829

  6. The model of fungal population dynamics affected by nystatin

    NASA Astrophysics Data System (ADS)

    Voychuk, Sergei I.; Gromozova, Elena N.; Sadovskiy, Mikhail G.

    Fungal diseases are acute problems of the up-to-day medicine. Significant increase of resistance of microorganisms to the medically used antibiotics and a lack of new effective drugs follows in a growth of dosage of existing chemicals to solve the problem. Quite often such approach results in side effects on humans. Detailed study of fungi-antibiotic dynamics can identify new mechanisms and bring new ideas to overcome the microbial resistance with a lower dosage of antibiotics. In this study, the dynamics of the microbial population under antibiotic treatment was investigated. The effects of nystatin on the population of Saccharomyces cerevisiae yeasts were used as a model system. Nystatin effects were investigated both in liquid and solid media by viability tests. Dependence of nystatin action on osmotic gradient was evaluated in NaCl solutions. Influences of glucose and yeast extract were additionally analyzed. A "stepwise" pattern of the cell death caused by nystatin was the most intriguing. This pattern manifested in periodical changes of the stages of cell death against stages of resistance to the antibiotic. The mathematical model was proposed to describe cell-antibiotic interactions and nystatin viability effects in the liquid medium. The model implies that antibiotic ability to cause a cells death is significantly affected by the intracellular compounds, which came out of cells after their osmotic barriers were damaged

  7. How Does Self-Regulation Affect Computer-Programming Achievement in a Blended Context?

    ERIC Educational Resources Information Center

    Cigdem, Harun

    2015-01-01

    This study focuses on learners' self-regulation which is one of the essential skills for student achievement in blended courses. Research on learners' self-regulation skills in blended learning environments has gained popularity in recent years however only a few studies investigating the correlation between self-regulation skills and student…

  8. Linking Emotion Regulation Strategies to Affective Events and Negative Emotions at Work

    ERIC Educational Resources Information Center

    Diefendorff, James M.; Richard, Erin M.; Yang, Jixia

    2008-01-01

    This study examined the use of specific forms of emotion regulation at work, utilizing Gross's [Gross, J. J. (1998). "The emerging field of emotion regulation: An integrative review." "Review of General Psychology" 2, 271-299] process-based framework of emotion regulation as a guiding structure. In addition to examining employee self-reported…

  9. Does Leisure Time as a Stress Coping Resource Increase Affective Complexity? Applying the Dynamic Model of Affect (DMA).

    PubMed

    Qian, Xinyi Lisa; Yarnal, Careen M; Almeida, David M

    2013-01-01

    Affective complexity, a manifestation of psychological well-being, refers to the relative independence between positive and negative affect (PA, NA). According to the Dynamic Model of Affect (DMA), stressful situations lead to highly inverse PA-NA relationship, reducing affective complexity. Meanwhile, positive events can sustain affective complexity by restoring PA-NA independence. Leisure, a type of positive events, has been identified as a coping resource. This study used the DMA to assess whether leisure time helps restore affective complexity on stressful days. We found that on days with more leisure time than usual, an individual experienced less negative PA-NA relationship after daily stressful events. The finding demonstrates the value of leisure time as a coping resource and the DMA's contribution to coping research. PMID:24659826

  10. TACC3 protein regulates microtubule nucleation by affecting γ-tubulin ring complexes.

    PubMed

    Singh, Puja; Thomas, Geethu Emily; Gireesh, Koyikulangara K; Manna, Tapas K

    2014-11-14

    Centrosome-mediated microtubule nucleation is essential for spindle assembly during mitosis. Although γ-tubulin complexes have primarily been implicated in the nucleation process, details of the underlying mechanisms remain poorly understood. Here, we demonstrated that a member of the human transforming acidic coiled-coil (TACC) protein family, TACC3, plays a critical role in microtubule nucleation at the centrosome. In mitotic cells, TACC3 knockdown substantially affected the assembly of microtubules in the astral region and impaired microtubule nucleation at the centrosomes. The TACC3 depletion-induced mitotic phenotype was rescued by expression of the TACC3 C terminus predominantly consisting of the TACC domain, suggesting that the TACC domain plays an important role in microtubule assembly. Consistently, experiments with the recombinant TACC domain of TACC3 demonstrated that this domain possesses intrinsic microtubule nucleating activity. Co-immunoprecipitation and sedimentation experiments revealed that TACC3 mediates interactions with proteins of both the γ-tubulin ring complex (γ-TuRC) and the γ-tubulin small complex (γ-TuSC). Interestingly, TACC3 depletion resulted in reduced levels of γ-TuRC and increased levels of γ-TuSC, indicating that the assembly of γ-TuRC from γ-TuSC requires TACC3. Detailed analyses suggested that TACC3 facilitates the association of γ-TuSC-specific proteins with the proteins known to be involved in the assembly of γ-TuRC. Consistent with such a role for TACC3, the suppression of TACC3 disrupted localization of γ-TuRC proteins to the centrosome. Our findings reveal that TACC3 is involved in the regulation of microtubule nucleation at the centrosome and functions in the stabilization of the γ-tubulin ring complex assembly. PMID:25246530

  11. AUTOUBIQUITINATION OF BCA2 RING E3 LIGASE REGULATES ITS OWN STABILITY AND AFFECTS CELL MIGRATION

    PubMed Central

    Amemiya, Yutaka; Azmi, Peter; Seth, Arun

    2009-01-01

    Accumulating evidence suggests that ubiquitination plays a role in cancer by changing the function of key cellular proteins. Previously, we isolated BCA2 gene from a library enriched for breast tumor mRNAs. The BCA2 protein is a RING type E3 ubiquitin ligase and is overexpressed in human breast tumors. In order to deduce the biochemical and biological function of BCA2, we searched for BCA2 binding partners using human breast and fetal brain cDNA libraries and BacterioMatch two-hybrid system. We identified 62 interacting partners, majority of those were found to encode ubiquitin precursor proteins including ubiquitin C and ubiquitinA-52. Using several deletion and point mutants, we found that the BCA2 zinc finger (BZF) domain at the N-terminus specifically binds ubiquitin and ubiquitinated proteins. The autoubiquitination activity of BCA2, RING-H2 mutant, BZF mutant, and various lysine mutants of BCA2 were investigated. Our results indicate that the BCA2 protein is strongly ubiquitinated and no ubiquitination is detected with the BCA2 RING-H2 mutant, indicating that the RING domain is essential for autoubiquitination. Mutation of the K26 and K32 lysines in the BZF domain also abrogated autoubiquitination activity. Interestingly, mutation of the K232 and K260 lysines in and near the RING domain resulted in an increase in autoubiquitination activity. Additionally, in cellular migration assays, BCA2 mutants showed altered cell motility compared to wild-type BCA2. On the basis of these findings, we propose that BCA2 maybe an important factor regulating breast cancer cell migration/metastasis. We put-forward a novel model for BCA2 E3 ligase mediated cell regulation. PMID:18819927

  12. Emotion regulation of the affect-modulated startle reflex during different picture categories.

    PubMed

    Conzelmann, Annette; McGregor, Victoria; Pauli, Paul

    2015-09-01

    Previous studies on emotion regulation of the startle reflex found an increase in startle amplitude from down-, to non-, to up-regulation for pleasant and unpleasant stimuli. We wanted to clarify whether this regulation effect remains stable for different picture categories within pleasant and unpleasant picture sets. We assessed startle amplitude of 31 participants during down-, non-, or up-regulation of feelings elicited by pleasant erotic and adventure and unpleasant victim and threat pictures. Startle amplitude was smaller during adventure and erotic compared to victim and threat pictures and increased from down-, to non-, to up-regulation independently of the picture category. Results indicate that the motivational priming effect on startle modulation elicited by different picture categories is independent of emotion regulation instructions. In addition, the emotion regulation effect is independent of motivational priming effects. PMID:26061976

  13. Event-Related Potentials Reveal Preserved Attention Allocation but Impaired Emotion Regulation in Patients with Epilepsy and Comorbid Negative Affect

    PubMed Central

    De Taeye, Leen; Pourtois, Gilles; Meurs, Alfred; Boon, Paul; Vonck, Kristl; Carrette, Evelien; Raedt, Robrecht

    2015-01-01

    Patients with epilepsy have a high prevalence of comorbid mood disorders. This study aims to evaluate whether negative affect in epilepsy is associated with dysfunction of emotion regulation. Event-related potentials (ERPs) are used in order to unravel the exact electrophysiological time course and investigate whether a possible dysfunction arises during early (attention) and/or late (regulation) stages of emotion control. Fifty epileptic patients with (n = 25) versus without (n = 25) comorbid negative affect plus twenty-five matched controls were recruited. ERPs were recorded while subjects performed a face- or house-matching task in which fearful, sad or neutral faces were presented either at attended or unattended spatial locations. Two ERP components were analyzed: the early vertex positive potential (VPP) which is normally enhanced for faces, and the late positive potential (LPP) that is typically larger for emotional stimuli. All participants had larger amplitude of the early face-sensitive VPP for attended faces compared to houses, regardless of their emotional content. By contrast, in patients with negative affect only, the amplitude of the LPP was significantly increased for unattended negative emotional expressions. These VPP results indicate that epilepsy with or without negative affect does not interfere with the early structural encoding and attention selection of faces. However, the LPP results suggest abnormal regulation processes during the processing of unattended emotional faces in patients with epilepsy and comorbid negative affect. In conclusion, this ERP study reveals that early object-based attention processes are not compromised by epilepsy, but instead, when combined with negative affect, this neurological disease is associated with dysfunction during the later stages of emotion regulation. As such, these new neurophysiological findings shed light on the complex interplay of epilepsy with negative affect during the processing of emotional

  14. Supporting Affect Regulation in Children with Multiple Disabilities during Psychotherapy: A Multiple Case Design Study of Therapeutic Attachment

    ERIC Educational Resources Information Center

    Schuengel, C.; Sterkenburg, P. S.; Jeczynski, P.; Janssen, C. G. C.; Jongbloed, G.

    2009-01-01

    In a controlled multiple case design study, the development of a therapeutic relationship and its role in affect regulation were studied in 6 children with visual disabilities, severe intellectual disabilities, severe challenging behavior, and prolonged social deprivation. In the 1st phase, children had sessions with an experimental therapist…

  15. Individual differences in effects of child care quality: The role of child affective self-regulation and gender.

    PubMed

    Broekhuizen, Martine L; Aken, Marcel A G van; Dubas, Judith S; Mulder, Hanna; Leseman, Paul P M

    2015-08-01

    The current study investigated whether the relation between child care quality and children's socio-emotional behavior depended on children's affective self-regulation skills and gender. Participants were 545 children (Mage=27 months) from 60 center-based child care centers in the Netherlands. Multi-level analyses showed that children with low affective self-regulation skills or who were male demonstrated less teacher-rated social competence when exposed to relatively low quality child care. In addition, children with low affective self-regulation skills also showed more social competence in the case of relatively high quality child care, suggesting mechanisms of differential susceptibility. No main effects of child care quality or interactions were found for teacher- and parent-rated externalizing behavior. These findings emphasize the importance of considering children's affective self-regulation skills and gender in understanding the effects of child care quality. High quality child care can be a means to strengthen children's social development. PMID:26210737

  16. Procrastination, Self-Regulation Failure, Academic Life Satisfaction, and Affective Well-Being: Underregulation or Misregulation Form

    ERIC Educational Resources Information Center

    Balkis, Murat; Duru, Erdinç

    2016-01-01

    The aim of this study was to examine the role of self-regulation failure in procrastination. In addition, it also aimed to investigate the effects of procrastination on affective well-being and academic life satisfaction. Three hundred and twenty-eight undergraduate students participated in the study. The most obvious finding emerging from this…

  17. Age Differences in Affective and Cardiovascular Responses to a Negative Social Interaction: The Role of Goals, Appraisals, and Emotion Regulation

    ERIC Educational Resources Information Center

    Luong, Gloria; Charles, Susan T.

    2014-01-01

    Older adults often report less affective reactivity to interpersonal tensions than younger individuals, but few studies have directly investigated mechanisms explaining this effect. The current study examined whether older adults' differential endorsement of goals, appraisals, and emotion regulation strategies (i.e., conflict…

  18. Infant Affect and Affect Regulation during the Still-Face Paradigm with Mothers and Fathers: The Role of Infant Characteristics and Parental Sensitivity.

    ERIC Educational Resources Information Center

    Braungart-Rieker, Julia; Garwood, Molly Murphy; Powers, Bruce P.; Notaro, Paul C.

    1998-01-01

    Examined parents' and 4-month-old infants' behavior during face-to-face interactions. Results indicated that mothers and fathers were equally sensitive to their infants, and that infants' affect and regulatory behaviors were stable across mother-infant and father-infant situations in the still-face model. (BC)

  19. Glycerol Affects Root Development through Regulation of Multiple Pathways in Arabidopsis

    PubMed Central

    Hu, Jun; Zhang, Yonghong; Wang, Jinfang; Zhou, Yongming

    2014-01-01

    Glycerol metabolism has been well studied biochemically. However, the means by which glycerol functions in plant development is not well understood. This study aimed to investigate the mechanism underlying the effects of glycerol on root development in Arabidopsis thaliana. Exogenous glycerol inhibited primary root growth and altered lateral root development in wild-type plants. These phenotypes appeared concurrently with increased endogenous glycerol-3-phosphate (G3P) and H2O2 contents in seedlings, and decreased phosphate levels in roots. Upon glycerol treatment, G3P level and root development did not change in glycerol kinase mutant gli1, but G3P level increased in gpdhc1 and fad-gpdh mutants, which resulted in more severely impaired root development. Overexpression of the FAD-GPDH gene attenuated the alterations in G3P, phosphate and H2O2 levels, leading to increased tolerance to exogenous glycerol, which suggested that FAD-GPDH plays an important role in modulating this response. Free indole-3-acetic acid (IAA) content increased by 46%, and DR5pro::GUS staining increased in the stele cells of the root meristem under glycerol treatment, suggesting that glycerol likely alters normal auxin distribution. Decreases in PIN1 and PIN7 expression, β-glucuronidase (GUS) staining in plants expressing PIN7pro::GUS and green fluorescent protein (GFP) fluorescence in plants expressing PIN7pro::PIN7-GFP were observed, indicating that polar auxin transport in the root was downregulated under glycerol treatment. Analyses with auxin-related mutants showed that TIR1 and ARF7 were involved in regulating root growth under glycerol treatment. Glycerol-treated plants showed significant reductions in root meristem size and cell number as revealed by CYCB1;1pro::GUS staining. Furthermore, the expression of CDKA and CYCB1 decreased significantly in treated plants compared with control plants, implying possible alterations in cell cycle progression. Our data demonstrated that glycerol

  20. Glycerol affects root development through regulation of multiple pathways in Arabidopsis.

    PubMed

    Hu, Jun; Zhang, Yonghong; Wang, Jinfang; Zhou, Yongming

    2014-01-01

    Glycerol metabolism has been well studied biochemically. However, the means by which glycerol functions in plant development is not well understood. This study aimed to investigate the mechanism underlying the effects of glycerol on root development in Arabidopsis thaliana. Exogenous glycerol inhibited primary root growth and altered lateral root development in wild-type plants. These phenotypes appeared concurrently with increased endogenous glycerol-3-phosphate (G3P) and H2O2 contents in seedlings, and decreased phosphate levels in roots. Upon glycerol treatment, G3P level and root development did not change in glycerol kinase mutant gli1, but G3P level increased in gpdhc1 and fad-gpdh mutants, which resulted in more severely impaired root development. Overexpression of the FAD-GPDH gene attenuated the alterations in G3P, phosphate and H2O2 levels, leading to increased tolerance to exogenous glycerol, which suggested that FAD-GPDH plays an important role in modulating this response. Free indole-3-acetic acid (IAA) content increased by 46%, and DR5pro::GUS staining increased in the stele cells of the root meristem under glycerol treatment, suggesting that glycerol likely alters normal auxin distribution. Decreases in PIN1 and PIN7 expression, β-glucuronidase (GUS) staining in plants expressing PIN7pro::GUS and green fluorescent protein (GFP) fluorescence in plants expressing PIN7pro::PIN7-GFP were observed, indicating that polar auxin transport in the root was downregulated under glycerol treatment. Analyses with auxin-related mutants showed that TIR1 and ARF7 were involved in regulating root growth under glycerol treatment. Glycerol-treated plants showed significant reductions in root meristem size and cell number as revealed by CYCB1;1pro::GUS staining. Furthermore, the expression of CDKA and CYCB1 decreased significantly in treated plants compared with control plants, implying possible alterations in cell cycle progression. Our data demonstrated that glycerol

  1. The Magea gene cluster regulates male germ cell apoptosis without affecting the fertility in mice

    PubMed Central

    Hou, Siyuan; Xian, Li; Shi, Peiliang; Li, Chaojun; Lin, Zhaoyu; Gao, Xiang

    2016-01-01

    While apoptosis is essential for male germ cell development, improper activation of apoptosis in the testis can affect spermatogenesis and cause reproduction defects. Members of the MAGE-A (melanoma antigen family A) gene family are frequently clustered in mammalian genomes and are exclusively expressed in the testes of normal animals but abnormally activated in a wide variety of cancers. We investigated the potential roles of these genes in spermatogenesis by generating a mouse model with a 210-kb genomic deletion encompassing six members of the Magea gene cluster (Magea1, Magea2, Magea3, Magea5, Magea6 and Magea8). Male mice carrying the deletion displayed smaller testes from 2 months old with a marked increase in apoptotic germ cells in the first wave of spermatogenesis. Furthermore, we found that Magea genes prevented stress-induced spermatogenic apoptosis after N-ethyl-N-nitrosourea (ENU) treatment during the adult stage. Mechanistically, deletion of the Magea gene cluster resulted in a dramatic increase in apoptotic germ cells, predominantly spermatocytes, with activation of p53 and induction of Bax in the testes. These observations demonstrate that the Magea genes are crucial in maintaining normal testicular size and protecting germ cells from excessive apoptosis under genotoxic stress. PMID:27226137

  2. The Magea gene cluster regulates male germ cell apoptosis without affecting the fertility in mice.

    PubMed

    Hou, Siyuan; Xian, Li; Shi, Peiliang; Li, Chaojun; Lin, Zhaoyu; Gao, Xiang

    2016-01-01

    While apoptosis is essential for male germ cell development, improper activation of apoptosis in the testis can affect spermatogenesis and cause reproduction defects. Members of the MAGE-A (melanoma antigen family A) gene family are frequently clustered in mammalian genomes and are exclusively expressed in the testes of normal animals but abnormally activated in a wide variety of cancers. We investigated the potential roles of these genes in spermatogenesis by generating a mouse model with a 210-kb genomic deletion encompassing six members of the Magea gene cluster (Magea1, Magea2, Magea3, Magea5, Magea6 and Magea8). Male mice carrying the deletion displayed smaller testes from 2 months old with a marked increase in apoptotic germ cells in the first wave of spermatogenesis. Furthermore, we found that Magea genes prevented stress-induced spermatogenic apoptosis after N-ethyl-N-nitrosourea (ENU) treatment during the adult stage. Mechanistically, deletion of the Magea gene cluster resulted in a dramatic increase in apoptotic germ cells, predominantly spermatocytes, with activation of p53 and induction of Bax in the testes. These observations demonstrate that the Magea genes are crucial in maintaining normal testicular size and protecting germ cells from excessive apoptosis under genotoxic stress. PMID:27226137

  3. How Is Emotional Awareness Related to Emotion Regulation Strategies and Self-Reported Negative Affect in the General Population?

    PubMed Central

    Subic-Wrana, Claudia; Beutel, Manfred E.; Brähler, Elmar; Stöbel-Richter, Yve; Knebel, Achim; Lane, Richard D.; Wiltink, Jörg

    2014-01-01

    Objective The Levels of Emotional Awareness Scale (LEAS) as a performance task discriminates between implicit or subconscious and explicit or conscious levels of emotional awareness. An impaired awareness of one's feeling states may influence emotion regulation strategies and self-reports of negative emotions. To determine this influence, we applied the LEAS and self-report measures for emotion regulation strategies and negative affect in a representative sample of the German general population. Sample and Methods A short version of the LEAS, the Hospital Anxiety and Depression Scale (HADS) and the Emotion Regulation Questionnaire (ERQ), assessing reappraisal and suppression as emotion regulation strategies, were presented to N = 2524 participants of a representative German community study. The questionnaire data were analyzed with regard to the level of emotional awareness. Results LEAS scores were independent from depression, but related to self-reported anxiety. Although of small or medium effect size, different correlational patters between emotion regulation strategies and negative affectivity were related to implict and explict levels of emotional awareness. In participants with implicit emotional awareness, suppression was related to higher anxiety and depression, whereas in participants with explicit emotional awareness, in addition to a positive relationship of suppression and depression, we found a negative relationship of reappraisal to depression. These findings were independent of age. In women high use of suppression and little use of reappraisal were more strongly related to negative affect than in men. Discussion Our first findings suggest that conscious awareness of emotions may be a precondition for the use of reappraisal as an adaptive emotion regulation strategy. They encourage further research in the relation between subconsious and conscious emotional awareness and the prefarance of adaptive or maladaptive emotion regulation strategies The

  4. Modelling and Analysis of a New Piezoelectric Dynamic Balance Regulator

    PubMed Central

    Du, Zhe; Mei, Xue-Song; Xu, Mu-Xun

    2012-01-01

    In this paper, a new piezoelectric dynamic balance regulator, which can be used in motorised spindle systems, is presented. The dynamic balancing adjustment mechanism is driven by an in-plane bending vibration from an annular piezoelectric stator excited by a high-frequency sinusoidal input voltage. This device has different construction, characteristics and operating principles than a conventional balance regulator. In this work, a dynamic model of the regulator is first developed using a detailed analytical method. Thereafter, MATLAB is employed to numerically simulate the relations between the dominant parameters and the characteristics of the regulator based on thedynamic model. Finally, experimental measurements are used to certify the validity of the dynamic model. Consequently, the mathematical model presented and analysed in this paper can be used as a tool for optimising the design of a piezoelectric dynamic balance regulator during steady state operation. PMID:23202182

  5. Differential regulation of Gli proteins by Sufu in the lung affects PDGF signaling and myofibroblast development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammalian Hedgehog (Hh) signaling relies on three Gli transcription factors to mediate Hh responses. This process is controlled in part by a major negative regulator, Sufu, through its effects on Gli protein level, distribution and activity. In this report, we showed that Sufu regulates Gli1 protein...

  6. Do Child Care Regulations Affect the Child Care and Labor Markets?

    ERIC Educational Resources Information Center

    Blau, David M.

    2003-01-01

    The effect of child care regulations on outcomes in the child care market and the labor market for mothers of young children is examined. The analysis uses a time series of cross sections and examines the robustness of previous cross-section findings to controls for state-level heterogeneity. Child care regulations as a group have statistically…

  7. How Do Motivational Regulation Strategies Affect Achievement: Mediated by Effort Management and Moderated by Intelligence

    ERIC Educational Resources Information Center

    Schwinger, Malte; Steinmayr, Ricarda; Spinath, Birgit

    2009-01-01

    It was assumed that the effect of motivational regulation strategies on achievement is mediated by effort management and moderated by intelligence. A sample of 231 11th and 12th grade German high-school students provided self-reports on their use of motivational regulation strategies and effort management and completed an intelligence test.…

  8. Children's Negative Emotionality Combined with Poor Self-Regulation Affects Allostatic Load in Adolescence

    ERIC Educational Resources Information Center

    Dich, Nadya; Doan, Stacey; Evans, Gary

    2015-01-01

    The present study examined the concurrent and prospective, longitudinal effects of childhood negative emotionality and self-regulation on allostatic load (AL), a physiological indicator of chronic stress. We hypothesized that negative emotionality in combination with poor self-regulation would predict elevated AL. Mothers reported on children's…

  9. The ASYMMETRIC LEAVES Complex Employs Multiple Modes of Regulation to Affect Adaxial-Abaxial Patterning and Leaf Complexity[OPEN

    PubMed Central

    Husbands, Aman Y.; Benkovics, Anna H.; Nogueira, Fabio T.S.; Lodha, Mukesh; Timmermans, Marja C.P.

    2015-01-01

    Flattened leaf architecture is not a default state but depends on positional information to precisely coordinate patterns of cell division in the growing primordium. This information is provided, in part, by the boundary between the adaxial (top) and abaxial (bottom) domains of the leaf, which are specified via an intricate gene regulatory network whose precise circuitry remains poorly defined. Here, we examined the contribution of the ASYMMETRIC LEAVES (AS) pathway to adaxial-abaxial patterning in Arabidopsis thaliana and demonstrate that AS1-AS2 affects this process via multiple, distinct regulatory mechanisms. AS1-AS2 uses Polycomb-dependent and -independent mechanisms to directly repress the abaxial determinants MIR166A, YABBY5, and AUXIN RESPONSE FACTOR3 (ARF3), as well as a nonrepressive mechanism in the regulation of the adaxial determinant TAS3A. These regulatory interactions, together with data from prior studies, lead to a model in which the sequential polarization of determinants, including AS1-AS2, explains the establishment and maintenance of adaxial-abaxial leaf polarity. Moreover, our analyses show that the shared repression of ARF3 by the AS and trans-acting small interfering RNA (ta-siRNA) pathways intersects with additional AS1-AS2 targets to affect multiple nodes in leaf development, impacting polarity as well as leaf complexity. These data illustrate the surprisingly multifaceted contribution of AS1-AS2 to leaf development showing that, in conjunction with the ta-siRNA pathway, AS1-AS2 keeps the Arabidopsis leaf both flat and simple. PMID:26589551

  10. Dynamical Analysis of bantam-Regulated Drosophila Circadian Rhythm Model

    NASA Astrophysics Data System (ADS)

    Li, Ying; Liu, Zengrong

    MicroRNAs (miRNAs) interact with 3‧untranslated region (UTR) elements of target genes to regulate mRNA stability or translation, and play a crucial role in regulating many different biological processes. bantam, a conserved miRNA, is involved in several functions, such as regulating Drosophila growth and circadian rhythm. Recently, it has been discovered that bantam plays a crucial role in the core circadian pacemaker. In this paper, based on experimental observations, a detailed dynamical model of bantam-regulated circadian clock system is developed to show the post-transcriptional behaviors in the modulation of Drosophila circadian rhythm, in which the regulation of bantam is incorporated into a classical model. The dynamical behaviors of the model are consistent with the experimental observations, which shows that bantam is an important regulator of Drosophila circadian rhythm. The sensitivity analysis of parameters demonstrates that with the regulation of bantam the system is more sensitive to perturbations, indicating that bantam regulation makes it easier for the organism to modulate its period against the environmental perturbations. The effectiveness in rescuing locomotor activity rhythms of mutated flies shows that bantam is necessary for strong and sustained rhythms. In addition, the biological mechanisms of bantam regulation are analyzed, which may help us more clearly understand Drosophila circadian rhythm regulated by other miRNAs.

  11. Psychometric properties of the Greek TCI-R and its clinical correlates: schizotypy and the self-regulation of affective and cognitive functioning.

    PubMed

    Giakoumaki, Stella G; Karagiannopoulou, Leda; Rózsa, Sándor; Zouraraki, Chrysoula; Karamaouna, Penny; Cloninger, C Robert

    2016-01-01

    Background. The revised Temperament and Character Inventory (TCI-R) measures Cloninger's psychobiological model of personality. The average effects of individual temperament and character traits have been associated with schizotypy and with impaired regulation of affect and cognition. We extended prior research by testing predictions about the association of specific multidimensional configurations of temperament and character traits on schizotypy, affect balance, and self-perceived cognitive functioning. Method. A well-educated sample of native Greeks (N = 483), completed a new Greek translation of the TCI-R, as well as the Schizotypal Personality Questionnaire (SPQ), the Positive/Negative Affect Schedule (PANAS) and the Cognitive Failures Questionnaire (CFQ). The factor structure of the TCI-R was examined with exploratory and confirmatory tests. Associations between reported measures were examined with correlational and regression analyses. Results. The TCI-R had good psychometric properties as expected from studies in other countries. As predicted, specific configurations of temperament and character were associated with schizotypy, negative affect balance, and cognitive lapses. The "Borderline/Explosive temperament" (high Novelty Seeking, high Harm Avoidance, low Reward Dependence), "Schizotypal/Disorganized character" (low Self-directedness, low Cooperativeness, high Self-transcendence), and "Low Ego Strength/Fragile" profile (high Harm Avoidance, low Persistence, low Self-Directedness) were each strongly associated with higher stereotypy, negative affect balance (low positive affect and high negative affect), and subjective cognitive lapses compared to their contrast groups. Discussion. Multidimensional TCI profiles are strongly related to individual differences in schizotypy and self-reported regulation of affect and cognition. The Greek translation of the TCI-R is psychometrically sound and useful for clinical assessment and research. PMID:27019787

  12. Psychometric properties of the Greek TCI-R and its clinical correlates: schizotypy and the self-regulation of affective and cognitive functioning

    PubMed Central

    Karagiannopoulou, Leda; Rózsa, Sándor; Zouraraki, Chrysoula; Karamaouna, Penny; Cloninger, C. Robert

    2016-01-01

    Background. The revised Temperament and Character Inventory (TCI-R) measures Cloninger’s psychobiological model of personality. The average effects of individual temperament and character traits have been associated with schizotypy and with impaired regulation of affect and cognition. We extended prior research by testing predictions about the association of specific multidimensional configurations of temperament and character traits on schizotypy, affect balance, and self-perceived cognitive functioning. Method. A well-educated sample of native Greeks (N = 483), completed a new Greek translation of the TCI-R, as well as the Schizotypal Personality Questionnaire (SPQ), the Positive/Negative Affect Schedule (PANAS) and the Cognitive Failures Questionnaire (CFQ). The factor structure of the TCI-R was examined with exploratory and confirmatory tests. Associations between reported measures were examined with correlational and regression analyses. Results. The TCI-R had good psychometric properties as expected from studies in other countries. As predicted, specific configurations of temperament and character were associated with schizotypy, negative affect balance, and cognitive lapses. The “Borderline/Explosive temperament” (high Novelty Seeking, high Harm Avoidance, low Reward Dependence), “Schizotypal/Disorganized character” (low Self-directedness, low Cooperativeness, high Self-transcendence), and “Low Ego Strength/Fragile” profile (high Harm Avoidance, low Persistence, low Self-Directedness) were each strongly associated with higher stereotypy, negative affect balance (low positive affect and high negative affect), and subjective cognitive lapses compared to their contrast groups. Discussion. Multidimensional TCI profiles are strongly related to individual differences in schizotypy and self-reported regulation of affect and cognition. The Greek translation of the TCI-R is psychometrically sound and useful for clinical assessment and research. PMID

  13. Thermodynamic model of heterochromatin formation through epigenetic regulation

    NASA Astrophysics Data System (ADS)

    Mulligan, Peter J.; Koslover, Elena F.; Spakowitz, Andrew J.

    2015-02-01

    Gene regulation in eukaryotes requires the segregation of silenced genomic regions into densely packed heterochromatin, leaving the active genes in euchromatin regions more accessible. We introduce a model that connects the presence of epigenetically inherited histone marks, methylation at histone 3 lysine-9, to the physical compaction of chromatin fibers via the binding of heterochromatin protein 1 (HP1). Our model demonstrates some of the key physical features that are necessary to explain experimental observations. In particular, we demonstrate that strong cooperative interactions among the HP1 proteins are necessary to see the phase segregation of heterochromatin and euchromatin regions. We also explore how the cell can use the concentration of HP1 to control condensation and under what circumstances there is a threshold of methylation over which the fibers will compact. Finally, we consider how different potential in vivo fiber structures as well as the flexibility of the histone 3 tail can affect the bridging of HP1. Many of the observations that we make about the HP1 system are guided by general thermodynamics principles and thus could play a role in other DNA organizational processes such as the binding of linker histones.

  14. Thermodynamic model of heterochromatin formation through epigenetic regulation.

    PubMed

    Mulligan, Peter J; Koslover, Elena F; Spakowitz, Andrew J

    2015-02-18

    Gene regulation in eukaryotes requires the segregation of silenced genomic regions into densely packed heterochromatin, leaving the active genes in euchromatin regions more accessible. We introduce a model that connects the presence of epigenetically inherited histone marks, methylation at histone 3 lysine-9, to the physical compaction of chromatin fibers via the binding of heterochromatin protein 1 (HP1). Our model demonstrates some of the key physical features that are necessary to explain experimental observations. In particular, we demonstrate that strong cooperative interactions among the HP1 proteins are necessary to see the phase segregation of heterochromatin and euchromatin regions. We also explore how the cell can use the concentration of HP1 to control condensation and under what circumstances there is a threshold of methylation over which the fibers will compact. Finally, we consider how different potential in vivo fiber structures as well as the flexibility of the histone 3 tail can affect the bridging of HP1. Many of the observations that we make about the HP1 system are guided by general thermodynamics principles and thus could play a role in other DNA organizational processes such as the binding of linker histones. PMID:25563699

  15. Positioning of extracellular loop 1 affects pore gating of the cystic fibrosis transmembrane conductance regulator.

    PubMed

    Infield, Daniel T; Cui, Guiying; Kuang, Christopher; McCarty, Nael A

    2016-03-01

    The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is a chloride ion channel, the dysfunction of which directly leads to the life-shortening disease CF. Extracellular loop 1 (ECL1) of CFTR contains several residues involved in stabilizing the open state of the channel; some, including D110, are sites of disease-associated gating mutations. Structures from related proteins suggest that the position of CFTR's extracellular loops may change considerably during gating. To better understand the roles of ECL1 in CFTR function, we utilized functional cysteine cross-linking to determine the effects of modulation of D110C-CFTR and of a double mutant of D110C with K892C in extracellular loop 4 (ECL4). The reducing agent DTT elicited a large potentiation of the macroscopic conductance of D110C/K892C-CFTR, likely due to breakage of a spontaneous disulfide bond between C110 and C892. DTT-reduced D110C/K892C-CFTR was rapidly inhibited by binding cadmium ions with high affinity, suggesting that these residues frequently come in close proximity in actively gating channels. Effects of DTT and cadmium on modulation of pore gating were demonstrated at the single-channel level. Finally, disulfided D110C/K892C-CFTR channels were found to be less sensitive than wild-type or DTT-treated D110C/K892C-CFTR channels to stimulation by IBMX, suggesting an impact of this conformational restriction on channel activation by phosphorylation. The results are best explained in the context of a model of CFTR gating wherein stable channel opening requires correct positioning of functional elements structurally influenced by ECL1. PMID:26684250

  16. Identification of Common Regulators of Genes in Co-Expression Networks Affecting Muscle and Meat Properties

    PubMed Central

    Ponsuksili, Siriluck; Siengdee, Puntita; Du, Yang; Trakooljul, Nares; Murani, Eduard; Schwerin, Manfred; Wimmers, Klaus

    2015-01-01

    Understanding the genetic contributions behind skeletal muscle composition and metabolism is of great interest in medicine and agriculture. Attempts to dissect these complex traits combine genome-wide genotyping, expression data analyses and network analyses. Weighted gene co-expression network analysis (WGCNA) groups genes into modules based on patterns of co-expression, which can be linked to phenotypes by correlation analysis of trait values and the module eigengenes, i.e. the first principal component of a given module. Network hub genes and regulators of the genes in the modules are likely to play an important role in the emergence of respective traits. In order to detect common regulators of genes in modules showing association with meat quality traits, we identified eQTL for each of these genes, including the highly connected hub genes. Additionally, the module eigengene values were used for association analyses in order to derive a joint eQTL for the respective module. Thereby major sites of orchestrated regulation of genes within trait-associated modules were detected as hotspots of eQTL of many genes of a module and of its eigengene. These sites harbor likely common regulators of genes in the modules. We exemplarily showed the consistent impact of candidate common regulators on the expression of members of respective modules by RNAi knockdown experiments. In fact, Cxcr7 was identified and validated as a regulator of genes in a module, which is involved in the function of defense response in muscle cells. Zfp36l2 was confirmed as a regulator of genes of a module related to cell death or apoptosis pathways. The integration of eQTL in module networks enabled to interpret the differentially-regulated genes from a systems perspective. By integrating genome-wide genomic and transcriptomic data, employing co-expression and eQTL analyses, the study revealed likely regulators that are involved in the fine-tuning and synchronization of genes with trait

  17. Identification of common regulators of genes in co-expression networks affecting muscle and meat properties.

    PubMed

    Ponsuksili, Siriluck; Siengdee, Puntita; Du, Yang; Trakooljul, Nares; Murani, Eduard; Schwerin, Manfred; Wimmers, Klaus

    2015-01-01

    Understanding the genetic contributions behind skeletal muscle composition and metabolism is of great interest in medicine and agriculture. Attempts to dissect these complex traits combine genome-wide genotyping, expression data analyses and network analyses. Weighted gene co-expression network analysis (WGCNA) groups genes into modules based on patterns of co-expression, which can be linked to phenotypes by correlation analysis of trait values and the module eigengenes, i.e. the first principal component of a given module. Network hub genes and regulators of the genes in the modules are likely to play an important role in the emergence of respective traits. In order to detect common regulators of genes in modules showing association with meat quality traits, we identified eQTL for each of these genes, including the highly connected hub genes. Additionally, the module eigengene values were used for association analyses in order to derive a joint eQTL for the respective module. Thereby major sites of orchestrated regulation of genes within trait-associated modules were detected as hotspots of eQTL of many genes of a module and of its eigengene. These sites harbor likely common regulators of genes in the modules. We exemplarily showed the consistent impact of candidate common regulators on the expression of members of respective modules by RNAi knockdown experiments. In fact, Cxcr7 was identified and validated as a regulator of genes in a module, which is involved in the function of defense response in muscle cells. Zfp36l2 was confirmed as a regulator of genes of a module related to cell death or apoptosis pathways. The integration of eQTL in module networks enabled to interpret the differentially-regulated genes from a systems perspective. By integrating genome-wide genomic and transcriptomic data, employing co-expression and eQTL analyses, the study revealed likely regulators that are involved in the fine-tuning and synchronization of genes with trait

  18. Models of Self-regulated Learning: A Review.

    ERIC Educational Resources Information Center

    Puustinen, Minna; Pulkkinen, Lea

    2001-01-01

    Describes and compares the latest models of self-regulated learning, including those developed by M. Boekaerts, J. Borkowski, P. Pintrich, P. Winne, and B. Zimmerman. The comparison shows that theoretical background is an important differentiating feature. (SLD)

  19. Down-regulation of Wnt10a affects odontogenesis and proliferation in mesenchymal cells

    SciTech Connect

    Liu, Yang Han, Dong Wang, Lei Feng, Hailan

    2013-05-17

    Highlights: •Down-regulation of Wnt10a in dental mesenchymal cells impairs odontogenesis of reassociated tooth germs. •Dspp is down- and up-regulated after Wnt10a-knockdown and overexpression in dental mesenchymal cells. •Down-regulation of Wnt10a inhibits proliferation of dental mesenchymal cells. -- Abstract: The WNT10a mutation has been found in patients with abnormal odontogenesis. In mice, Wnt10a expression is found in the tooth germ, but its role has not yet been elucidated. We aimed to investigate the role of Wnt10a in odontogenesis. Mesenchymal cells of the first mandibular molar germ at the bell stage were isolated, transfected with Wnt10a SiRNA or plasmid, and reassociated with epithelial part of the molar germ. Scrambled SiRNA or empty vector was used in the control group. The reassociated tooth germs were transplanted into mice subrenal capsules. After gene modification, dental mesenchymal cells cultured in vitro were checked for cell proliferation and the expression of Dspp was examined. All 12 reassociated tooth germs in the control group resumed odontogenesis, while only 5 of 12 in the Wnt10a knockdown group developed into teeth. After Wnt10a knockdown, the mesenchymal cells cultured in vitro presented repressed proliferation. Wnt10a knockdown and overexpression led to both down- and up-regulation of Dspp. We conclude that the down-regulation of Wnt10a impairs odontogensis and cell proliferation, and that Wnt10a regulates Dspp expression in mesenchymal cells. These findings help to elucidate the mechanism of abnormal tooth development in patients with the WNT10A mutation.

  20. A cAMP-Regulated Chloride Channel in Lymphocytes that is Affected in Cystic Fibrosis

    NASA Astrophysics Data System (ADS)

    Chen, Jennifer H.; Schulman, Howard; Gardner, Phyllis

    1989-02-01

    A defect in regulation of a chloride channel appears to be the molecular basis for cystic fibrosis (CF), a common lethal genetic disease. It is shown here that a chloride channel with kinetic and regulatory properties similar to those described for secretory epithelial cells is present in both T and B lymphocyte cell lines. The regulation of the channels by adenosine 3',5'-monophosphate (cAMP)--dependent protein kinase in transformed B cells from CF patients is defective. Thus, lymphocytes may be an accessible source of CF tissue for study of this defect, for cloning of the chloride channel complex, and for diagnosis of the disease.

  1. Integrating affective and cognitive correlates of heart rate variability: A structural equation modeling approach.

    PubMed

    Mann, Sarah L; Selby, Edward A; Bates, Marsha E; Contrada, Richard J

    2015-10-01

    High frequency heart rate variability (HRV) is a measure of neurocardiac communication thought to reflect predominantly parasympathetic cardiac regulation. Low HRV has been associated empirically with clinical and subclinical levels of anxiety and depression and, more recently, high levels of HRV have been associated with better performance on some measures of executive functioning (EF). These findings have offered support for theories proposing HRV as an index measure of a broad, self-regulatory capacity underlying aspects of emotion regulation and executive control. This study sought to test that proposition by using a structural equation modeling approach to examine the relationships of HRV to negative affect (NA) and EF in a large sample of U.S. adults ages 30s-80s. HRV was modeled as a predictor of an NA factor (self-reported trait anxiety and depression symptoms) and an EF factor (performance on three neuropsychological tests tapping facets of executive abilities). Alternative models also were tested to determine the utility of HRV for predicting NA and EF, with and without statistical control of demographic and health-related covariates. In the initial structural model, HRV showed a significant positive relationship to EF and a nonsignificant relationship to NA. In a covariate-adjusted model, HRV's associations with both constructs were nonsignificant. Age emerged as the only significant predictor of NA and EF in the final model, showing inverse relationships to both. Findings may reflect population and methodological differences from prior research; they also suggest refinements to the interpretations of earlier findings and theoretical claims regarding HRV. PMID:26168884

  2. Transcriptional regulation differs in affected facioscapulohumeral muscular dystrophy patients compared to asymptomatic related carriers

    PubMed Central

    Arashiro, Patricia; Eisenberg, Iris; Kho, Alvin T.; Cerqueira, Antonia M. P.; Canovas, Marta; Silva, Helga C. A.; Pavanello, Rita C. M.; Verjovski-Almeida, Sergio; Kunkel, Louis M.; Zatz, Mayana

    2009-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disorder that has been associated with a contraction of 3.3-kb repeats on chromosome 4q35. FSHD is characterized by a wide clinical inter- and intrafamilial variability, ranging from wheelchair-bound patients to asymptomatic carriers. Our study is unique in comparing the gene expression profiles from related affected, asymptomatic carrier, and control individuals. Our results suggest that the expression of genes on chromosome 4q is altered in affected and asymptomatic individuals. Remarkably, the changes seen in asymptomatic samples are largely in products of genes encoding several chemokines, whereas the changes seen in affected samples are largely in genes governing the synthesis of GPI-linked proteins and histone acetylation. Besides this, the affected patient and related asymptomatic carrier share the 4qA161 haplotype. Thus, these polymorphisms by themselves do not explain the pathogenicity of the contracted allele. Interestingly, our results also suggest that the miRNAs might mediate the regulatory network in FSHD. Together, our results support the previous evidence that FSHD may be caused by transcriptional dysregulation of multiple genes, in cis and in trans, and suggest some factors potentially important for FSHD pathogenesis. The study of the gene expression profiles from asymptomatic carriers and related affected patients is a unique approach to try to enhance our understanding of the missing link between the contraction in D4Z4 repeats and muscle disease, while minimizing the effects of differences resulting from genetic background. PMID:19339494

  3. Determinants affecting physical activity levels in animal models

    NASA Technical Reports Server (NTRS)

    Tou, Janet C L.; Wade, Charles E.

    2002-01-01

    Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play an underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multifactorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked, making it difficult to determine whether a single, combination, or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to the ventral medial hypothalamus, and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.

  4. Determinants Affecting Physical Activity Levels In Animal Models

    NASA Technical Reports Server (NTRS)

    Tou, Janet C. L.; Wade, Charles E.; Dalton, Bonnie P. (Technical Monitor)

    2001-01-01

    Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play all underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multi-factorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked making it difficult to determine whether a single, combination or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to tile ventral medial hypothalamus and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.

  5. Affective regulation of stereotype activation: It’s the (accessible) thought that counts

    PubMed Central

    Huntsinger, Jeffrey R.; Sinclair, Stacey; Dunn, Elizabeth; Clore, Gerald L.

    2010-01-01

    Extant research demonstrates that positive affect, compared to negative affect, increases stereotyping. In four experiments we explore whether the link between affect and stereotyping depends, critically, on the relative accessibility of stereotype-relevant thoughts and response tendencies. As well as manipulating mood, we measured or manipulated the accessibility of egalitarian response tendencies (Experiments 1-2) and counter-stereotypic thoughts (Experiments 3-4). In the absence of such response tendencies and thoughts, people in positive moods displayed greater stereotype activation —consistent with past research. By contrast, in the presence of accessible egalitarian response tendencies or counter-stereotypic thoughts, people in positive moods exhibited less stereotype activation than those in negative moods. PMID:20363909

  6. Mutations in the bvgA gene of Bordetella pertussis that differentially affect regulation of virulence determinants.

    PubMed Central

    Stibitz, S

    1994-01-01

    By using chemical mutagenesis and genetic mapping, a search was undertaken for previously undescribed genes which may be involved in different regulatory mechanisms governing different virulence factors of Bordetella pertussis. Previous studies have shown that the fha locus encoding filamentous hemagglutinin is regulated directly by the bvgAS two component system, while regulation of ptx encoding pertussis toxin is less direct or occurs by a different mechanism. With a strain containing gene fusions to each of these regulated loci, screening was done for mutations which were defective for ptx expression but maintained normal or nearly normal levels of fha expression. Two mutations which had such a phenotype and were also deficient in adenylate cyclase toxin/hemolysin expression were found and characterized more fully. Both were found to affect residues in the C-terminal portion of the BvgA response regulator protein, a domain which shares sequence similarity with a family of regulatory proteins including FixJ, UhpA, MalT, RcsA, RcsB, and LuxR. The residues affected are within a region which, by extension from studies on the LuxR protein, may be involved in transcriptional activation. Images PMID:8083156

  7. Mother-infant dyadic reparation and individual differences in vagal tone affect 4-month-old infants' social stress regulation.

    PubMed

    Provenzi, Livio; Casini, Erica; de Simone, Paola; Reni, Gianluigi; Borgatti, Renato; Montirosso, Rosario

    2015-12-01

    Infants' social stress regulation (i.e., reactivity and recovery) might be affected by mother-infant dyadic functioning and infants' vagal tone (i.e., respiratory sinus arrhythmia, RSA). This study investigated the role of a specific dyadic functioning feature (i.e., dyadic reparation) and individual differences in vagal tone regulation (i.e., RSA suppression vs. non-suppression) in relation to social stress regulation in 4-month-old infants. A total of 65 mother-infant dyads participated in the face-to-face still-face paradigm. Social stress reactivity and recovery were measured as negative emotionality during Still-Face and Reunion episodes, respectively. RSA was measured during Play, Still-Face, and Reunion episodes. Suppressors had higher dyadic reparation during Play and higher recovery from social stress compared with non-suppressors. Higher reparation during Play was associated with lower reactivity and higher recovery only for suppressors. Findings suggest a joint role of infants' RSA individual differences and dyadic reparation in affecting infants' social stress regulation at 4 months of age. PMID:26247809

  8. Hypothalamic Dopaminergic Neurons in an Animal Model of Seasonal Affective Disorder

    PubMed Central

    Deats, Sean P.; Adidharma, Widya; Yan, Lily

    2015-01-01

    Light has profound effects on mood regulation as exemplified in Seasonal Affective Disorder (SAD) and the therapeutic benefits of light therapy. However, the underlying neural pathways through which light regulates mood are not well understood. Our previous work has developed the diurnal grass rat, Arvicanthis niloticus, as an animal model of SAD. Following housing conditions of either 12:12hr Dim Light:Dark (DLD) or 8:16hr Short Photoperiod (SP), which mimic the lower light intensity or short day-length of winter, respectively, grass rats exhibit an increase in depression-like behavior compared to those housed in a 12:12hr Bright Light:Dark (BLD) condition. Furthermore, we revealed that the orexinergic system is involved in mediating the effects of light on mood and anxiety. To explore other potential neural substrates involved in the depressive phenotype, the present study examined hypothalamic dopaminergic (DA) and somatostatin (SST) neurons in the brains of grass rats housed in DLD, SP and BLD. Using immunostaining for tyrosine hydroxylase (TH) and SST, we found that the number of TH- and SST-ir cells in the hypothalamus was significantly lower in the DLD and SP groups compared to the BLD group. We also found that treating BLD animals with a selective orexin receptor 1 (OX1R) antagonist SB-334867 significantly reduced the number of hypothalamic TH-ir cells. The present study suggests that the hypothalamic DA neurons are sensitive to daytime light deficiency and are regulated by an orexinergic pathway. The results support the hypothesis that the orexinergic pathways mediate the effects of light on other neuronal systems that collectively contribute to light-dependent changes in the affective state. PMID:26116821

  9. Emotion Regulation in Preschoolers: The Roles of Behavioral Inhibition, Maternal Affective Behavior, and Maternal Depression

    ERIC Educational Resources Information Center

    Feng, Xin; Shaw, Daniel S.; Kovacs, Maria; Lane, Tonya; O'Rourke, Flannery E.; Alarcon, Joseph H.

    2008-01-01

    Background: This study examined preschoolers' emotion regulation (ER) strategies and the association with temperament, maternal interactive style, and maternal history of childhood-onset depression (COD). Methods: Participants were 62 children and their mothers, 37 of whom had mothers with COD. Children's ER was assessed using a disappointment…

  10. Schizophrenia-Associated MIR204 Regulates Noncoding RNAs and Affects Neurotransmitter and Ion Channel Gene Sets

    PubMed Central

    Cammaerts, Sophia; Strazisar, Mojca; Smets, Bart; Weckhuysen, Sarah; Nordin, Annelie; De Jonghe, Peter; Adolfsson, Rolf; De Rijk, Peter; Del Favero, Jurgen

    2015-01-01

    As regulators of gene expression, microRNAs (miRNAs) are likely to play an important role in the development of disease. In this study we present a large-scale strategy to identify miRNAs with a role in the regulation of neuronal processes. Thereby we found variant rs7861254 located near the MIR204 gene to be significantly associated with schizophrenia. This variant resulted in reduced expression of miR-204 in neuronal-like SH-SY5Y cells. Analysis of the consequences of the altered miR-204 expression on the transcriptome of these cells uncovered a new mode of action for miR-204, being the regulation of noncoding RNAs (ncRNAs), including several miRNAs, such as MIR296. Furthermore, pathway analysis showed downstream effects of miR-204 on neurotransmitter and ion channel related gene sets, potentially mediated by miRNAs regulated through miR-204. PMID:26714269

  11. Computer-Based Science Inquiry: How Components of Metacognitive Self-Regulation Affect Problem-Solving.

    ERIC Educational Resources Information Center

    Howard, Bruce C.; McGee, Steven; Shia, Regina; Hong, Namsoo Shin

    This study sought to examine the effects of meta cognitive self-regulation on problem solving across three conditions: (1) an interactive, computer-based treatment condition; (2) a noninteractive computer-based alternative treatment condition; and (3) a control condition. Also investigated was which of five components of metacognitive…

  12. Methodological Implications of the Affect Revolution: A 35-Year Review of Emotion Regulation Assessment in Children

    ERIC Educational Resources Information Center

    Adrian, Molly; Zeman, Janice; Veits, Gina

    2011-01-01

    This investigation analyzed the methods used over the past 35 years to study emotion regulation (ER) in children. Articles published from 1975 through 2010 were identified in 42 child clinical, developmental, and emotion psychology journals. Overall, 61.1% of published ER articles relied on one method and 23.6% used two methods. Analyses revealed…

  13. Thapsigargin affects presenilin-2 but not presenilin-1 regulation in SK-N-BE cells.

    PubMed

    Rivabene, Roberto; Visentin, Sergio; Piscopo, Paola; De Nuccio, Chiara; Crestini, Alessio; Svetoni, Francesca; Rosa, Paolo; Confaloni, Annamaria

    2014-02-01

    Presenilin-1 (PS1) and presenilin-2 (PS2) are transmembrane proteins widely expressed in the central nervous system, which function as the catalytic subunits of γ-secretase, the enzyme that releases amyloid-β protein (Aβ) from ectodomain cleaved amyloid precursor protein (APP) by intramembrane proteolysis. Mutations in PS1, PS2, and Aβ protein precursor are involved in the etiology of familial Alzheimer's disease (FAD), while the cause of the sporadic form of AD (SAD) is still not known. However, since similar neuropathological changes have been observed in both FAD and SAD, a common pathway in the etiology of the disease has been suggested. Given that age-related deranged Ca(2+) regulation has been hypothesized to play a role in SAD pathogenesis via PS gene regulation and γ-secretase activity, we studied the in vitro regulation of PS1 and PS2 in the human neuron-like SK-N-BE cell line treated with the specific endoplasmic reticulum (ER) calcium ATPase inhibitor Thapsigargin (THG), to introduce intracellular Ca(2+) perturbations and mimic the altered Ca(2+) homeostasis observed in AD. Our results showed a consistent and significant down-regulation of PS2, while PS1 appeared to be unmodulated. These events were accompanied by oxidative stress and a number of morphological alterations suggestive of the induction of apoptotic machinery. The administration of the antioxidant N-acetylcysteine (NAC) did not revert the THG-induced effects reported, while treatment with the Ca(2+)-independent ER stressor Brefeldin A did not modulate basal PS1 and PS2 expression. Collectively, these results suggest that Ca(2+) fluctuation rather than ER stress and/or oxidative imbalance seems to play an essential role in PS2 regulation and confirm that, despite their strong homology, PS1 and PS2 could play different roles in AD. PMID:24363250

  14. Comparing Multiple Discrepancies Theory to Affective Models of Subjective Wellbeing

    ERIC Educational Resources Information Center

    Blore, Jed D.; Stokes, Mark A.; Mellor, David; Firth, Lucy; Cummins, Robert A.

    2011-01-01

    The Subjective Wellbeing (SWB) literature is replete with competing theories detailing the mechanisms underlying the construction and maintenance of SWB. The current study aimed to compare and contrast two of these approaches: multiple discrepancies theory (MDT) and an affective-cognitive theory of SWB. MDT posits SWB to be the result of perceived…

  15. Clinical models of cardiovascular regulation after weightlessness

    NASA Technical Reports Server (NTRS)

    Robertson, D.; Jacob, G.; Ertl, A.; Shannon, J.; Mosqueda-Garcia, R.; Robertson, R. M.; Biaggioni, I.

    1996-01-01

    After several days in microgravity, return to earth is attended by alterations in cardiovascular function. The mechanisms underlying these effects are inadequately understood. Three clinical disorders of autonomic function represent possible models of this abnormal cardiovascular function after spaceflight. They are pure autonomic failure, baroreflex failure, and orthostatic intolerance. In pure autonomic failure, virtually complete loss of sympathetic and parasympathetic function occurs along with profound and immediate orthostatic hypotension. In baroreflex failure, various degrees of debuffering of blood pressure occur. In acute and complete baroreflex failure, there is usually severe hypertension and tachycardia, while with less complete and more chronic baroreflex impairment, orthostatic abnormalities may be more apparent. In orthostatic intolerance, blood pressure fall is minor, but orthostatic symptoms are prominent and tachycardia frequently occurs. Only careful autonomic studies of human subjects in the microgravity environment will permit us to determine which of these models most closely reflects the pathophysiology brought on by a period of time in the microgravity environment.

  16. Overview of U.S. Legislation and Regulations Affecting Offshore Natural Gas and Oil Activity

    EIA Publications

    2005-01-01

    This article presents a summary of the legislative and regulatory regime that affects natural gas and oil exploration and production in offshore regions of the United States. It discusses the role and importance of these areas as well as the competing interests surrounding ownership, production, exploration and conservation.

  17. Pluralistic and stochastic gene regulation: examples, models and consistent theory

    PubMed Central

    Salas, Elisa N.; Shu, Jiang; Cserhati, Matyas F.; Weeks, Donald P.; Ladunga, Istvan

    2016-01-01

    We present a theory of pluralistic and stochastic gene regulation. To bridge the gap between empirical studies and mathematical models, we integrate pre-existing observations with our meta-analyses of the ENCODE ChIP-Seq experiments. Earlier evidence includes fluctuations in levels, location, activity, and binding of transcription factors, variable DNA motifs, and bursts in gene expression. Stochastic regulation is also indicated by frequently subdued effects of knockout mutants of regulators, their evolutionary losses/gains and massive rewiring of regulatory sites. We report wide-spread pluralistic regulation in ≈800 000 tightly co-expressed pairs of diverse human genes. Typically, half of ≈50 observed regulators bind to both genes reproducibly, twice more than in independently expressed gene pairs. We also examine the largest set of co-expressed genes, which code for cytoplasmic ribosomal proteins. Numerous regulatory complexes are highly significant enriched in ribosomal genes compared to highly expressed non-ribosomal genes. We could not find any DNA-associated, strict sense master regulator. Despite major fluctuations in transcription factor binding, our machine learning model accurately predicted transcript levels using binding sites of 20+ regulators. Our pluralistic and stochastic theory is consistent with partially random binding patterns, redundancy, stochastic regulator binding, burst-like expression, degeneracy of binding motifs and massive regulatory rewiring during evolution. PMID:26823500

  18. Pluralistic and stochastic gene regulation: examples, models and consistent theory.

    PubMed

    Salas, Elisa N; Shu, Jiang; Cserhati, Matyas F; Weeks, Donald P; Ladunga, Istvan

    2016-06-01

    We present a theory of pluralistic and stochastic gene regulation. To bridge the gap between empirical studies and mathematical models, we integrate pre-existing observations with our meta-analyses of the ENCODE ChIP-Seq experiments. Earlier evidence includes fluctuations in levels, location, activity, and binding of transcription factors, variable DNA motifs, and bursts in gene expression. Stochastic regulation is also indicated by frequently subdued effects of knockout mutants of regulators, their evolutionary losses/gains and massive rewiring of regulatory sites. We report wide-spread pluralistic regulation in ≈800 000 tightly co-expressed pairs of diverse human genes. Typically, half of ≈50 observed regulators bind to both genes reproducibly, twice more than in independently expressed gene pairs. We also examine the largest set of co-expressed genes, which code for cytoplasmic ribosomal proteins. Numerous regulatory complexes are highly significant enriched in ribosomal genes compared to highly expressed non-ribosomal genes. We could not find any DNA-associated, strict sense master regulator. Despite major fluctuations in transcription factor binding, our machine learning model accurately predicted transcript levels using binding sites of 20+ regulators. Our pluralistic and stochastic theory is consistent with partially random binding patterns, redundancy, stochastic regulator binding, burst-like expression, degeneracy of binding motifs and massive regulatory rewiring during evolution. PMID:26823500

  19. Age Differences in Affective and Cardiovascular Responses to a Negative Social Interaction: The Role of Goals, Appraisals, and Emotion Regulation

    PubMed Central

    Luong, Gloria; Charles, Susan T.

    2014-01-01

    Older adults often report less affective reactivity to interpersonal tensions than younger individuals, but few studies have directly investigated mechanisms explaining this effect. The current study examined whether older adults’ differential endorsement of goals, appraisals, and emotion regulation strategies (i.e., conflict avoidance/de-escalation, self-distraction) during a controlled negative social interaction may explain age differences in affective and cardiovascular responses to the conflict discussion. Participants (N=159; 80 younger adults, 79 older adults) discussed hypothetical dilemmas with disagreeable confederates. Throughout the laboratory session, participants’ subjective emotional experience, blood pressure, and pulse rate were assessed. Older adults generally exhibited less reactivity (negative affect reactivity, diastolic blood pressure reactivity, and pulse rate reactivity) to the task, and more pronounced positive and negative affect recovery following the task, than did younger adults. Older adults appraised the task as more enjoyable and the confederate as more likeable, and more strongly endorsed goals to perform well on the task, which mediated age differences in negative affect reactivity, pulse rate reactivity, and positive affect recovery (i.e., increases in post-task positive affect), respectively. In addition, younger adults showed increased negative affect reactivity with greater use of self-distraction, whereas older adults did not. Together, findings suggest that older adults respond less negatively to unpleasant social interactions than younger adults, and these responses are explained in part by older adults’ pursuit of different motivational goals, less threatening appraisals of the social interaction, and more effective use of self-distraction, compared to younger adults. PMID:24773101

  20. Stress and affective disorders: animal models elucidating the molecular basis of neuroendocrine-behavior interactions.

    PubMed

    Touma, C

    2011-05-01

    Profound dysfunctions in several neuroendocrine systems have been described in patients suffering from affective disorders such as major depression. In order to elucidate the mechanisms underlying these functional alterations, animal models including mice genetically modified by either direct gene-targeting or by selective breeding approaches have been used exceedingly, revealing valuable insights into neuroendocrine pathways conserved between rodents and men. This review focuses on altered function and regulation of the hypothalamic-pituitary-adrenocortical axis, including its involvement in emotionality and stress responsiveness. In this context, the corticotropin-releasing hormone system and disturbances in glucocorticoid receptor signaling seem to be of central importance. However, changes in the expression and release patterns of vasopressin, dopamine and serotonin have also been shown to contribute to variation in emotionality, stress coping, cognitive functions and social behaviors. Affective disorders show a high degree of complexity, involving a multitude of molecular, neuroendocrine, and behavioral alterations as well as an intense gene-environment interaction, making it difficult to dissociate the primary causes from secondary consequences of the disease. Thus, interdisciplinary research, as applied in the emerging field of systems biology, involving adequate animal models and combined methodologies can significantly contribute to our understanding regarding the transmission of genetic predispositions into clinically relevant endophenotypes. It is only with deep insight into the mechanisms by which the stress hormone systems are regulated that novel treatment strategies and promising targets for therapeutic interventions can be developed in the future. Such in-depth understanding is ultimately essential to realizing our goal of predictive, preventive, and personalized medicine. PMID:21544741

  1. From analog to digital models of gene regulation

    NASA Astrophysics Data System (ADS)

    Munsky, Brian; Neuert, Gregor

    2015-07-01

    Recently, major progress has been made to develop computational models to predict and explain the mechanisms and behaviors of gene regulation. Here, we review progress on how these mechanisms and behaviors have been interpreted with analog models, where cell properties continuously modulate transcription, and digital models, where gene modulation involves discrete activation and inactivation events. We introduce recent experimental approaches, which measure these gene regulatory behaviors at single-cell and single-molecule resolution, and we discuss the integration of these approaches with computational models to reveal biophysical insight. By analyzing simple toy models in the context of existing experimental capabilities, we discuss the interplay between different experiments and different models to measure and interpret gene regulatory behaviors. Finally, we review recent successes in the development of predictive computational models for the control of gene regulation behaviors.

  2. From Analog to Digital Models of Gene Regulation

    PubMed Central

    Munsky, Brian; Neuert, Gregor

    2015-01-01

    Recently, major progress has been made to develop computational models to predict and explain the mechanisms and behaviors of gene regulation. Here, we review progress on how these mechanisms and behaviors have been interpreted with analog models, where cell properties continuously modulate transcription, and digital models, where gene modulation involves discrete activation and inactivation events. We introduce recent experimental approaches, which measure these gene regulatory behaviors at single-cell and single-molecule resolution, and we discuss the integration of these approaches with computational models to reveal biophysical insight. By analyzing simple toy models in the context of existing experimental capabilities, we discuss the interplay between different experiments and different models to measure and interpret gene regulatory behaviors. Finally, we review recent successes in the development of predictive computational models for the control of gene regulation behaviors. PMID:26086470

  3. In Ovo injection of betaine affects hepatic cholesterol metabolism through epigenetic gene regulation in newly hatched chicks.

    PubMed

    Hu, Yun; Sun, Qinwei; Li, Xiaoliang; Wang, Min; Cai, Demin; Li, Xi; Zhao, Ruqian

    2015-01-01

    Betaine is reported to regulate hepatic cholesterol metabolism in mammals. Chicken eggs contain considerable amount of betaine, yet it remains unknown whether and how betaine in the egg affects hepatic cholesterol metabolism in chicks. In this study, eggs were injected with betaine at 2.5 mg/egg and the hepatic cholesterol metabolism was investigated in newly hatched chicks. Betaine did not affect body weight or liver weight, but significantly increased the serum concentration (P < 0.05) and the hepatic content (P < 0.01) of cholesterol. Accordingly, the cholesterol biosynthetic enzyme HMGCR was up-regulated (P < 0.05 for both mRNA and protein), while CYP7A1 which converts cholesterol to bile acids was down-regulated (P < 0.05 for mRNA and P = 0.07 for protein). Moreover, hepatic protein content of the sterol-regulatory element binding protein 1 which regulates cholesterol and lipid biosynthesis, and the mRNA abundance of ATP binding cassette sub-family A member 1 (ABCA1) which mediates cholesterol counter transport were significantly (P < 0.05) increased in betaine-treated chicks. Meanwhile, hepatic protein contents of DNA methyltransferases 1 and adenosylhomocysteinase-like 1 were increased (P < 0.05), which was associated with global genomic DNA hypermethylation (P < 0.05) and diminished gene repression mark histone H3 lysine 27 trimethylation (P < 0.05). Furthermore, CpG methylation level on gene promoters was found to be increased (P < 0.05) for CYP7A1 yet decreased (P < 0.05) for ABCA1. These results indicate that in ovo betaine injection regulates hepatic cholesterol metabolism in chicks through epigenetic mechanisms including DNA and histone methylations. PMID:25860502

  4. In Ovo Injection of Betaine Affects Hepatic Cholesterol Metabolism through Epigenetic Gene Regulation in Newly Hatched Chicks

    PubMed Central

    Hu, Yun; Sun, Qinwei; Li, Xiaoliang; Wang, Min; Cai, Demin; Li, Xi; Zhao, Ruqian

    2015-01-01

    Betaine is reported to regulate hepatic cholesterol metabolism in mammals. Chicken eggs contain considerable amount of betaine, yet it remains unknown whether and how betaine in the egg affects hepatic cholesterol metabolism in chicks. In this study, eggs were injected with betaine at 2.5 mg/egg and the hepatic cholesterol metabolism was investigated in newly hatched chicks. Betaine did not affect body weight or liver weight, but significantly increased the serum concentration (P < 0.05) and the hepatic content (P < 0.01) of cholesterol. Accordingly, the cholesterol biosynthetic enzyme HMGCR was up-regulated (P < 0.05 for both mRNA and protein), while CYP7A1 which converts cholesterol to bile acids was down-regulated (P < 0.05 for mRNA and P = 0.07 for protein). Moreover, hepatic protein content of the sterol-regulatory element binding protein 1 which regulates cholesterol and lipid biosynthesis, and the mRNA abundance of ATP binding cassette sub-family A member 1 (ABCA1) which mediates cholesterol counter transport were significantly (P < 0.05) increased in betaine-treated chicks. Meanwhile, hepatic protein contents of DNA methyltransferases 1 and adenosylhomocysteinase-like 1 were increased (P < 0.05), which was associated with global genomic DNA hypermethylation (P < 0.05) and diminished gene repression mark histone H3 lysine 27 trimethylation (P < 0.05). Furthermore, CpG methylation level on gene promoters was found to be increased (P < 0.05) for CYP7A1 yet decreased (P < 0.05) for ABCA1. These results indicate that in ovo betaine injection regulates hepatic cholesterol metabolism in chicks through epigenetic mechanisms including DNA and histone methylations. PMID:25860502

  5. [Mathematical model of baroreflex regulation of hemodynamics in the dog].

    PubMed

    Palets, B L

    1983-11-01

    A non-linear mathematical model of dog hemodynamics regulation was developed including descriptions of the cardiovascular system, the arterial baroreflex and the Beinbridge reflex. Model calculated arterial and venous pressure, blood flow, and heart rate are in good agreement with experimental data. PMID:6653829

  6. The Conceptual Framework of Factors Affecting Shared Mental Model

    ERIC Educational Resources Information Center

    Lee, Miyoung; Johnson, Tristan; Lee, Youngmin; O'Connor, Debra; Khalil, Mohammed

    2004-01-01

    Many researchers have paid attention to the potentiality and possibility of the shared mental model because it enables teammates to perform their job better by sharing team knowledge, skills, attitudes, dynamics and environments. Even though theoretical and experimental evidences provide a close relationship between the shared mental model and…

  7. Modifications to the translational apparatus which affect the regulation of protein synthesis in sea urchin embryos

    SciTech Connect

    Scalise, F.W.

    1988-01-01

    Protein synthesis can be regulated at a number of cellular levels. I have examined how modifications to specific components of the protein synthetic machinery are involved in regulating the efficiency of initiation of translation during early sea urchin embryogenesis. It is demonstrated that Ca{sup 2+} concentrations exceeding 500 uM cause the inhibition of protein synthesis in cell-free translation lysates prepared from sea urchin embryos. Specific changes in the state of phosphorylation of at least 8 proteins occur during this Ca{sup 2+}-mediated repression of translation. Analysis of these proteins has indicated that, unlike mammalian systems, there is no detectable level of Ca{sup 2+}-dependent phosphorylation of the {alpha}subunit eIF-2. Two of the proteins which do become phosphorylated in response to Ca{sup 2+} are calmodulin and an isoelectric form of sea urchin eIF-4D. In addition, 2 proteins which share similarities with kinases involved in the regulation of protein synthesis in mammalian cells, also become phosphorylated. I have investigated the consequences of changes in eIF-4D during sea urchin embryogenesis because it has been proposed that a polyamine-mediated conversion of lysine to hypusine in this factor may enhance translational activity. It is demonstrated that ({sup 3}H) spermidine-derived radioactivity is incorporated into a number of proteins when sea urchin embryos are labeled in vivo, and that the pattern of individual proteins that become labeled changes over the course of the first 30 hr of development.

  8. Perfectionism, Emotion Regulation and Their Relationship to Negative Affect in Patients with Social Phobia

    PubMed Central

    Rukmini, Systla; Sudhir, Paulomi M.; Math, Suresh Bada

    2014-01-01

    Context: Research on the perfectionism and emotion regulation strategies in anxiety disorders has gained increased attention. These have an important implication for formulation of therapies. Aims: We examined perfectionism, emotion regulation were examined in 30 patients with social phobia (SP) and 30 community participants. Settings and Design: A cross-sectional design using a clinical and a community control sample was adopted in this exploratory study. Materials and Methods: Participants were assessed on The Mini-International Neuropsychiatric Interview, Frost's-Multidimensional Perfectionism Scale, Ruminative Response Scale of the response style questionnaire, cognitive emotion regulation questionnaire, Social Interaction Anxiety Scale and the Beck's Depression Inventory. Statistical Analysis: Data was analyzed using independents samples t-test and Pearson's Product moment correlations and step-wise linear regression. Results: Individuals with SP had higher perfectionism (mean = 100.30, SD = ±17.73, t = 7.29, P < 0.001), rumination (mean = 61.47, SD = ±11.96, t = 6.71, P < 0.001) and lower levels of positive reappraisal (mean = 11.53, SD = ±3.85, t = 4.90, P < 0.001). Perfectionism was correlated with social anxiety (r = 0.44, P < 0.05) and rumination (r = 0.43, P < 0.05), but not with depression. Rumination was positively correlated with both social anxiety (r = 0.513, P < 0.01) and depression (r = 0.485, P < 0.01). Positive reappraisal was negatively correlated with depression (r = -0.396, P < 0.05) and anxiety (r = -0.335, P < 0.05). Acceptance was found to be significantly correlated only to the reflective pondering subscale of rumination. Parental criticism was a significant predictor of social anxiety (F = 11.11, P < 0.01) and brooding predicted depression (F = 10.49, P < 0.01). Conclusions: This study highlights the role of perfectionism as a maintaining factor in SP and the importance of adaptive forms of emotion regulation that need to be addressed

  9. GOLDEN 2-LIKE transcription factors for chloroplast development affect ozone tolerance through the regulation of stomatal movement.

    PubMed

    Nagatoshi, Yukari; Mitsuda, Nobutaka; Hayashi, Maki; Inoue, Shin-Ichiro; Okuma, Eiji; Kubo, Akihiro; Murata, Yoshiyuki; Seo, Mitsunori; Saji, Hikaru; Kinoshita, Toshinori; Ohme-Takagi, Masaru

    2016-04-12

    Stomatal movements regulate gas exchange, thus directly affecting the efficiency of photosynthesis and the sensitivity of plants to air pollutants such as ozone. The GARP family transcription factors GOLDEN 2-LIKE1 (GLK1) and GLK2 have known functions in chloroplast development. Here, we show that Arabidopsis thaliana (A. thaliana) plants expressing the chimeric repressors for GLK1 and -2 (GLK1/2-SRDX) exhibited a closed-stomata phenotype and strong tolerance to ozone. By contrast, plants that overexpress GLK1/2 exhibited an open-stomata phenotype and higher sensitivity to ozone. The plants expressing GLK1-SRDX had reduced expression of the genes for inwardly rectifying K(+) (K(+) in) channels and reduced K(+) in channel activity. Abscisic acid treatment did not affect the stomatal phenotype of 35S:GLK1/2-SRDX plants or the transcriptional activity for K(+) in channel gene, indicating that GLK1/2 act independently of abscisic acid signaling. Our results indicate that GLK1/2 positively regulate the expression of genes for K(+) in channels and promote stomatal opening. Because the chimeric GLK1-SRDX repressor driven by a guard cell-specific promoter induced a closed-stomata phenotype without affecting chloroplast development in mesophyll cells, modulating GLK1/2 activity may provide an effective tool to control stomatal movements and thus to confer resistance to air pollutants. PMID:27035938

  10. Mutant cohesin affects RNA polymerase II regulation in Cornelia de Lange syndrome

    PubMed Central

    Mannini, Linda; C. Lamaze, Fabien; Cucco, Francesco; Amato, Clelia; Quarantotti, Valentina; Rizzo, Ilaria M; Krantz, Ian D; Bilodeau, Steve; Musio, Antonio

    2015-01-01

    In addition to its role in sister chromatid cohesion, genome stability and integrity, the cohesin complex is involved in gene transcription. Mutations in core cohesin subunits SMC1A, SMC3 and RAD21, or their regulators NIPBL and HDAC8, cause Cornelia de Lange syndrome (CdLS). Recent evidence reveals that gene expression dysregulation could be the underlying mechanism for CdLS. These findings raise intriguing questions regarding the potential role of cohesin-mediated transcriptional control and pathogenesis. Here, we identified numerous dysregulated genes occupied by cohesin by combining the transcriptome of CdLS cell lines carrying mutations in SMC1A gene and ChIP-Seq data. Genome-wide analyses show that genes changing in expression are enriched for cohesin-binding. In addition, our results indicate that mutant cohesin impairs both RNA polymerase II (Pol II) transcription initiation at promoters and elongation in the gene body. These findings highlight the pivotal role of cohesin in transcriptional regulation and provide an explanation for the typical gene dysregulation observed in CdLS patients. PMID:26581180

  11. A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity

    PubMed Central

    Hammer, Christian; Wanitchakool, Podchanart; Sirianant, Lalida; Papiol, Sergi; Monnheimer, Mathieu; Faria, Diana; Ousingsawat, Jiraporn; Schramek, Natalie; Schmitt, Corinna; Margos, Gabriele; Michel, Angelika; Kraiczy, Peter; Pawlita, Michael; Schreiber, Rainer; Schulz, Thomas F; Fingerle, Volker; Tumani, Hayrettin; Ehrenreich, Hannelore; Kunzelmann, Karl

    2015-01-01

    In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin 10 (ANO10), a member of a protein family encoding Cl− channels and phospholipid scram-blases. ANO10 augments volume-regulated Cl− currents (IHypo) in Xenopus oocytes, HEK293 cells, lymphocytes and macrophages and controls volume regulation by enhancing regulatory volume decrease (RVD). ANO10 supports migration of macrophages and phagocytosis of spirochetes. The R263H variant is inhibitory on IHypo, RVD and intracellular Ca2+ signals, which may delay spirochete clearance, thereby sensitizing adaptive immunity. Our data demonstrate for the first time that ANO10 has a central role in innate immune defense against Borrelia infection. PMID:25730773

  12. Identification of a New Class of Negative Regulators Affecting Sporulation-Specific Gene Expression in Yeast

    PubMed Central

    Benni, M. L.; Neigeborn, L.

    1997-01-01

    We characterized two yeast loci, MDS3 and PMD1, that negatively regulate sporulation. Initiation of sporulation is mediated by the meiotic activator IME1, which relies on MCK1 for maximal expression. We isolated the MDS3-1 allele (encoding a truncated form of Mds3p) as a suppressor that restores IME1 expression in mck1 mutants. mds3 null mutations confer similar suppression phenotypes as MDS3-1, indicating that Mds3p is a negative regulator of sporulation and the MDS3-1 allele confers a dominant-negative phenotype. PMD1 is predicted to encode a protein sharing significant similarity with Mds3p. mds3 pmd1 double mutants are better suppressors of mck1 than is either single mutant, indicating that Mds3p and Pmd1p function synergistically. Northern blot analysis revealed that suppression is due to increased IME1 transcript accumulation. The roles of Mds3p and Pmd1p are not restricted to the MCK1 pathway because mds3 pmd1 mutations also suppress IME1 expression defects associated with MCK1-independent sporulation mutants. Furthermore, mds3 pmd1 mutants express significant levels of IME1 even in vegetative cells and this unscheduled expression results in premature sporulation. These phenotypes and interactions with RAS2-Val19 suggest that unscheduled derepression of IME1 is probably due to a defect in recognition of nutritional status. PMID:9383076

  13. Nitric oxide-mediated blood flow regulation as affected by smoking and nicotine.

    PubMed

    Toda, Noboru; Toda, Hiroshi

    2010-12-15

    Cigarette smoking is a major risk factor for atherosclerosis, cerebral and coronary vascular diseases, hypertension, and diabetes mellitus. Chronic smoking impairs endothelial function by decreasing the formation of nitric oxide and increasing the degradation of nitric oxide via generation of oxygen free radicals. Nitric oxide liberated from efferent nitrergic nerves is also involved in vasodilatation, increased regional blood flow, and hypotension that are impaired through nitric oxide sequestering by smoking-induced factors. Influence of smoking on nitric oxide-induced blood flow regulation is not necessarily the same in all organs and tissues. However, human studies are limited mainly to the forearm blood flow measurement that assesses endothelial function under basal and stimulated conditions and also determination of penile tumescence and erection in response to endothelial and neuronal nitric oxide. Therefore, information about blood flow regulation in other organs, such as the brain and placenta, has been provided mainly from studies on experimental animals. Nicotine, a major constituent of cigarette smoke, acutely dilates cerebral arteries and arterioles through nitric oxide liberated from nitrergic neurons, but chronically interferes with endothelial function in various vasculatures, both being noted in studies on experimental animals. Cigarette smoke constituents other than nicotine also have some vascular actions. Not only active but also passive smoking is undoubtedly harmful for both the smokers themselves and their neighbors, who should bear in mind that they can face serious diseases in the future, which may result in lengthy hospitalization, and a shortened lifespan. PMID:20868673

  14. A modeling approach for compounds affecting body composition.

    PubMed

    Gennemark, Peter; Jansson-Löfmark, Rasmus; Hyberg, Gina; Wigstrand, Maria; Kakol-Palm, Dorota; Håkansson, Pernilla; Hovdal, Daniel; Brodin, Peter; Fritsch-Fredin, Maria; Antonsson, Madeleine; Ploj, Karolina; Gabrielsson, Johan

    2013-12-01

    Body composition and body mass are pivotal clinical endpoints in studies of welfare diseases. We present a combined effort of established and new mathematical models based on rigorous monitoring of energy intake (EI) and body mass in mice. Specifically, we parameterize a mechanistic turnover model based on the law of energy conservation coupled to a drug mechanism model. Key model variables are fat-free mass (FFM) and fat mass (FM), governed by EI and energy expenditure (EE). An empirical Forbes curve relating FFM to FM was derived experimentally for female C57BL/6 mice. The Forbes curve differs from a previously reported curve for male C57BL/6 mice, and we thoroughly analyse how the choice of Forbes curve impacts model predictions. The drug mechanism function acts on EI or EE, or both. Drug mechanism parameters (two to three parameters) and system parameters (up to six free parameters) could be estimated with good precision (coefficients of variation typically <20 % and not greater than 40 % in our analyses). Model simulations were done to predict the EE and FM change at different drug provocations in mice. In addition, we simulated body mass and FM changes at different drug provocations using a similar model for man. Surprisingly, model simulations indicate that an increase in EI (e.g. 10 %) was more efficient than an equal lowering of EI. Also, the relative change in body mass and FM is greater in man than in mouse at the same relative change in either EI or EE. We acknowledge that this assumes the same drug mechanism impact across the two species. A set of recommendations regarding the Forbes curve, vehicle control groups, dual action on EI and loss, and translational aspects are discussed. This quantitative approach significantly improves data interpretation, disease system understanding, safety assessment and translation across species. PMID:24158456

  15. Inhibition of the mevalonate pathway affects epigenetic regulation in cancer cells

    PubMed Central

    Karlic, Heidrun; Thaler, Roman; Gerner, Christopher; Grunt, Thomas; Proestling, Katharina; Haider, Florian; Varga, Franz

    2015-01-01

    The mevalonate pathway provides metabolites for post-translational modifications such as farnesylation, which are critical for the activity of RAS downstream signaling. Subsequently occurring regulatory processes can induce an aberrant stimulation of DNA methyltransferase (DNMT1) as well as changes in histone deacetylases (HDACs) and microRNAs in many cancer cell lines. Inhibitors of the mevalonate pathway are increasingly recognized as anticancer drugs. Extensive evidence indicates an intense cross-talk between signaling pathways, which affect growth, differentiation, and apoptosis either directly or indirectly via epigenetic mechanisms. Herein, we show data obtained by novel transcriptomic and corresponding methylomic or proteomic analyses from cell lines treated with pharmacologic doses of respective inhibitors (i.e., simvastatin, ibandronate). Metabolic pathways and their epigenetic consequences appear to be affected by a changed concentration of NADPH. Moreover, since the mevalonate metabolism is part of a signaling network, including vitamin D metabolism or fatty acid synthesis, the epigenetic activity of associated pathways is also presented. This emphasizes the far-reaching epigenetic impact of metabolic therapies on cancer cells and provides some explanation for clinical observations, which indicate the anticancer activity of statins and bisphosphonates. PMID:25978957

  16. Sodium houttuyfonate affects production of N-acyl homoserine lactone and quorum sensing-regulated genes expression in Pseudomonas aeruginosa

    PubMed Central

    Wu, Daqiang; Huang, Weifeng; Duan, Qiangjun; Li, Fang; Cheng, Huijuan

    2014-01-01

    Quorum sensing (QS) is a means of cell-to-cell communication that uses diffusible signaling molecules that are sensed by the population to determine population density, thus allowing co-ordinate gene regulation in response to population density. In Pseudomonas aeruginosa, production of the QS signaling molecule, N-acyl homoserine lactone (AHL), co-ordinates expression of key factors of pathogenesis, including biofilm formation and toxin secretion. It is predicted that the inhibition of AHL sensing would provide an effective clinical treatment to reduce the expression of virulence factors and increase the effectiveness of antimicrobial agents. We previously demonstrated that sodium houttuyfonate (SH), commonly used in traditional Chinese medicine to treat infectious diseases, can effectively inhibit QS-regulated processes, including biofilm formation. Here, using a model system, we demonstrate that SH causes the dose-dependent inhibition of AHL production, through down-regulation of the AHL biosynthesis gene, lasI. Addition of SH also resulted in down-regulation of expression of the AHL sensor and transcriptional regulator, LasR, and inhibited the production of the QS-regulated virulence factors, pyocyanin and LasA. These results suggest that the antimicrobial activity of SH may be due to its ability to disrupt QS in P. aeruginosa. PMID:25505457

  17. Ctr2 Regulates Mast Cell Maturation by Affecting the Storage and Expression of Tryptase and Proteoglycans.

    PubMed

    Öhrvik, Helena; Logeman, Brandon; Noguchi, Glyn; Eriksson, Inger; Kjellén, Lena; Thiele, Dennis J; Pejler, Gunnar

    2015-10-15

    Copper (Cu) is essential for multiple cellular functions. Cellular uptake of Cu(+) is carried out by the Ctr1 high-affinity Cu transporter. The mobilization of endosomal Cu pools is regulated by a protein structurally similar to Ctr1, called Ctr2. It was recently shown that ablation of Ctr2 caused an increase in the concentration of Cu localized to endolysosomes. However, the biological significance of excess endolysosomal Cu accumulation has not been assessed. In this study, we addressed this issue by investigating the impact of Ctr2 deficiency on mast cells, a cell type unusually rich in endolysosomal organelles (secretory granules). We show that Ctr2(-/-) mast cells have increased intracellular Cu concentrations and that the absence of Ctr2 results in increased metachromatic staining, the latter indicating an impact of Ctr2 on the storage of proteoglycans in the secretory granules. In agreement with this, the absence of Ctr2 caused a skewed ratio between proteoglycans of heparin and chondroitin sulfate type, with increased amounts of heparin accompanied by a reduction of chondroitin sulfate. Moreover, transmission electron microscopy analysis revealed a higher number of electron-dense granules in Ctr2(-/-) mast cells than in wild-type cells. The increase in granular staining and heparin content is compatible with an impact of Ctr2 on mast cell maturation and, in support of this, the absence of Ctr2 resulted in markedly increased mRNA expression, storage, and enzymatic activity of tryptase. Taken together, the present study introduces Ctr2 and Cu as novel actors in the regulation of mast cell maturation and granule homeostasis. PMID:26342034

  18. Models for financing the regulation of pharmaceutical promotion.

    PubMed

    Lexchin, Joel

    2012-01-01

    Pharmaceutical companies spend huge sums promoting their products whereas regulation of promotional activities is typically underfinanced. Any option for financing the monitoring and regulation of promotion should adhere to three basic principles: stability, predictability and lack of (perverse) ties between the level of financing and performance. This paper explores the strengths and weaknesses of six different models. All these six models considered here have positive and negative features and none may necessarily be ideal in any particular country. Different countries may choose to utilize a combination of two or more of these models in order to raise sufficient revenue. Financing of regulation of drug promotion should more than pay for itself through the prevention of unnecessary drug costs and the avoidance of adverse health effects due to inappropriate prescribing. However, it involves an initial outlay of money that is currently not being spent and many national governments, in both rich and poor countries, are unwilling to incur extra costs. PMID:22784944

  19. Models of Affective Decision Making: How Do Feelings Predict Choice?

    PubMed

    Charpentier, Caroline J; De Neve, Jan-Emmanuel; Li, Xinyi; Roiser, Jonathan P; Sharot, Tali

    2016-06-01

    Intuitively, how you feel about potential outcomes will determine your decisions. Indeed, an implicit assumption in one of the most influential theories in psychology, prospect theory, is that feelings govern choice. Surprisingly, however, very little is known about the rules by which feelings are transformed into decisions. Here, we specified a computational model that used feelings to predict choices. We found that this model predicted choice better than existing value-based models, showing a unique contribution of feelings to decisions, over and above value. Similar to the value function in prospect theory, our feeling function showed diminished sensitivity to outcomes as value increased. However, loss aversion in choice was explained by an asymmetry in how feelings about losses and gains were weighted when making a decision, not by an asymmetry in the feelings themselves. The results provide new insights into how feelings are utilized to reach a decision. PMID:27071751

  20. [The Influence of Puberty on Neural Systems Subserving Emotion Regulation: Implications for Understanding Risk for Affective Disorders].

    PubMed

    Ladouceur, Cecile D

    2016-01-01

    Adolescence, with the onset of puberty, represents a developmental period that, in the context of adverse events, renders youth vulnerable to the onset of psychopathology such as affective disorders. It is also a time when fronto-striatal-limbic systems supporting the processing and regulation of emotion and reward undergo important neuromaturational changes. Despite evidence from epidemiological research suggesting that, particularly in girls, the increase in the rate of depression is more strongly associated with pubertal development than maturational age, researchers are just beginning to scratch the surface regarding the specific influence of puberty on the development of fronto-striatal-limbic systems implicated in the pathophysiology of affective disorders. The goal of this review is to a) summarize findings from human neuroimaging studies focusing on the specific influence of puberty or sex hormones on the neurodevelopment of emotional processes, b) highlight the need for a better understanding of neurodevelopmental changes during puberty and how such changes could contribute to developmental trajectories toward the onset of an affective disorder and, c) discuss the potential value of investigating how these changes may contribute to unique opportunities for developing intervention strategies for affective disorders in adolescence. PMID:27570951

  1. Undulation frequency affects burial performance in living and model flatfishes.

    PubMed

    McKee, Amberle; MacDonald, Ian; Farina, Stacy C; Summers, Adam P

    2016-04-01

    Flatfishes bury themselves under a thin layer of sand to hide from predators or to ambush prey. We investigated the role of undulation frequency of the body in burial in five species of flatfishes (Isopsetta isolepis, Lepidopsetta bilineata, Hippoglossoides elassodon, Parophrys vetulus, and Psettichthys melanostictus). High-speed videos show that undulations begin cranially and pass caudally while burying, as in forward swimming in many other fishes. The flatfishes also flick the posterior edge of their dorsal and anal fins during burial, which may increase the total surface area covered by substrate. We built a simple physical model - a flexible, oval silicone plate with a motorized, variable-speed actuator - to isolate the effect of undulation frequency on burial. In both the model and actuated dead flatfish, increased undulation frequency resulted in an increase in the area of sand coverage. Complete coverage required an undulation frequency of no more than 10Hz for our models, and that was also sufficient for live flatfishes. The model shows that undulation is sufficient to bury the animal, but live flatfishes showed a superior ability to bury, which we attribute to the action of the median fins. PMID:26763759

  2. Coupled model of physical and biological processes affecting maize pollination

    NASA Astrophysics Data System (ADS)

    Arritt, R.; Westgate, M.; Riese, J.; Falk, M.; Takle, E.

    2003-04-01

    Controversy over the use of genetically modified (GM) crops has led to increased interest in evaluating and controlling the potential for inadvertent outcrossing in open-pollinated crops such as maize. In response to this problem we have developed a Lagrangian model of pollen dispersion as a component of a coupled end-to-end (anther to ear) physical-biological model of maize pollination. The Lagrangian method is adopted because of its generality and flexibility: first, the method readily accommodates flow fields of arbitrary complexity; second, each element of the material being transported can be identified by its source, time of release, or other properties of interest. The latter allows pollen viability to be estimated as a function of such factors as travel time, temperature, and relative humidity, so that the physical effects of airflow and turbulence on pollen dispersion can be considered together with the biological aspects of pollen release and viability. Predicted dispersion of pollen compares well both to observations and to results from a simpler Gaussian plume model. Ability of the Lagrangian model to handle complex air flows is demonstrated by application to pollen dispersion in the vicinity of an agricultural shelter belt. We also show results indicating that pollen viability can be quantified by an "aging function" that accounts for temperature, humidity, and time of exposure.

  3. In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation

    PubMed Central

    Palmieri, Dario; De Luca, Luciana; Consiglio, Jessica; You, Jia; Rocci, Alberto; Talabere, Tiffany; Piovan, Claudia; Lagana, Alessandro; Cascione, Luciano; Guan, Jingwen; Gasparini, Pierluigi; Balatti, Veronica; Nuovo, Gerard; Coppola, Vincenzo; Hofmeister, Craig C.; Marcucci, Guido; Byrd, John C.; Volinia, Stefano; Shapiro, Charles L.; Freitas, Michael A.

    2013-01-01

    Numerous studies have described the altered expression and the causal role of microRNAs (miRNAs) in human cancer. However, to date, efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here we find that nucleolin (NCL), a major nucleolar protein, posttranscriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, that are causally involved in breast cancer initiation, progression, and drug resistance. We also show that NCL is commonly overexpressed in human breast tumors and that its expression correlates with that of NCL-dependent miRNAs. Finally, inhibition of NCL using guanosine-rich aptamers reduces the levels of NCL-dependent miRNAs and their target genes, thus reducing breast cancer cell aggressiveness both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer. PMID:23610125

  4. In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation.

    PubMed

    Pichiorri, Flavia; Palmieri, Dario; De Luca, Luciana; Consiglio, Jessica; You, Jia; Rocci, Alberto; Talabere, Tiffany; Piovan, Claudia; Lagana, Alessandro; Cascione, Luciano; Guan, Jingwen; Gasparini, Pierluigi; Balatti, Veronica; Nuovo, Gerard; Coppola, Vincenzo; Hofmeister, Craig C; Marcucci, Guido; Byrd, John C; Volinia, Stefano; Shapiro, Charles L; Freitas, Michael A; Croce, Carlo M

    2013-05-01

    Numerous studies have described the altered expression and the causal role of microRNAs (miRNAs) in human cancer. However, to date, efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here we find that nucleolin (NCL), a major nucleolar protein, posttranscriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, that are causally involved in breast cancer initiation, progression, and drug resistance. We also show that NCL is commonly overexpressed in human breast tumors and that its expression correlates with that of NCL-dependent miRNAs. Finally, inhibition of NCL using guanosine-rich aptamers reduces the levels of NCL-dependent miRNAs and their target genes, thus reducing breast cancer cell aggressiveness both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer. PMID:23610125

  5. Study of the impacts of regulations affecting the acceptance of integrated community energy systems. Final report

    SciTech Connect

    Feurer, Duane A.; Weaver, Clifford L.; Rielley, Kevin J.; Gallagher, Kevin C.; Harmon, Susan B.; Hejna, David T.; Kitch, Edmund W.

    1981-01-01

    A detailed description is presented of the laws and programs of the State of North Carolina governing the regulation of public energy utilities, the siting of energy generating and transmission facilities, the municipal franchising of public energy utilities, and the prescription of rates to be charged by utilities including attendant problems of cost allocations, rate base and operating expense determinations, and rate of return allowances. These laws and programs are analyzed to identify impediments which they may present to the implementation of Integrated Community Energy Systems (ICES). This report is one of fifty-one separate volumes which describe such regulatory programs at the Federal level and in each state as background to the report entitled Community Energy Systems and the Law of Public Utilities - Volume One: An Overview. This report also contains a summary of a strategy described in Volume One - An Overview for overcoming these impediments by working within the existing regulatory framework and by making changes in the regulatory programs to enhance the likelihood of ICES implementation.

  6. Transcription of Interleukin-8: How Altered Regulation Can Affect Cystic Fibrosis Lung Disease.

    PubMed

    Jundi, Karim; Greene, Catherine M

    2015-01-01

    Interleukin-8 (IL-8) is a neutrophil chemokine that is encoded on the CXCL8 gene. Normally CXCL8 expression is repressed due to histone deacetylation, octamer-1 binding to the promoter and the inhibitory effect of nuclear factor-κB repressing factor (NRF). However, in response to a suitable stimulus, the human CXCL8 gene undergoes transcription due to its inducible promoter that is regulated by the transcription factors nuclear factor-κB (NF-κB), activating protein (AP-1), CAAT/enhancer-binding protein β (C/EBPβ, also known as NF-IL-6), C/EBP homologous protein (CHOP) and cAMP response element binding protein (CREB). CXCL8 mRNA is then stabilised by the activity of p38 mitogen-activated protein kinase (p38 MAPK). Cystic fibrosis (CF) lung disease is characterised by a neutrophil-dominated airway inflammatory response. A major factor contributing to the large number of neutrophils is the higher than normal levels of IL-8 that are present within the CF lung. Infection and inflammation, together with intrinsic alterations in CF airway cells are responsible for the abnormally high intrapulmonary levels of IL-8. Strategies to inhibit aberrantly high CXCL8 expression hold therapeutic potential for CF lung disease. PMID:26140537

  7. Insulin-regulated aminopeptidase in adipocyte is Cys-specific and affected by obesity.

    PubMed

    Alponti, Rafaela Fadoni; Viana, Luciana Godoy; Yamanouye, Norma; Silveira, Paulo Flavio

    2015-08-01

    Insulin-regulated aminopeptidase (IRAP, EC 3.4.11.3) in adipocytes is well known to traffic between high (HDM) and low (LDM) density microsomal fractions toward the plasma membrane (MF) under stimulation by insulin. However, its catalytic preference for aminoacyl substrates with N-terminal Leu or Cys is controversial. Furthermore, possible changes in its traffic under metabolic challenges are unknown. The present study investigated the catalytic activity attributable to EC 3.4.11.3 in HDM, LDM and MF from isolated adipocytes of healthy (C), food deprived (FD) and monosodium glutamate (MSG) obese rats on aminoacyl substrates with N-terminal Cys or Leu, in absence or presence of insulin. Efficacy and reproducibility of subcellular adipocyte fractionation procedure were demonstrated. Comparison among HDM vs LDM vs MF intragroup revealed that hydrolytic activity trafficking from LDM to MF under influence of insulin in C, MSG and FD is only on N-terminal Cys. In MSG the same pattern of anterograde traffic and aminoacyl preference occurred independently of insulin stimulation. The pathophysiological significance of IRAP in adipocytes seems to be linked to comprehensive energy metabolism related roles of endogenous substrates with N-terminal cysteine pair such as vasopressin and oxytocin. PMID:25999180

  8. Models, Regulations, and Functions of Microtubule Severing by Katanin

    PubMed Central

    Ghosh, Debasish Kumar; Dasgupta, Debdeep; Guha, Abhishek

    2012-01-01

    Regulation of microtubule dynamics depends on stochastic balance between polymerization and severing process which lead to differential spatiotemporal abundance and distribution of microtubules during cell development, differentiation, and morphogenesis. Microtubule severing by a conserved AAA family protein Katanin has emerged as an important microtubule architecture modulating process in cellular functions like division, migration, shaping and so on. Regulated by several factors, Katanin manifests connective crosstalks in network motifs in regulation of anisotropic severing pattern of microtubule protofilaments in cell type and stage dependent way. Mechanisms of structural disintegration of microtubules by Katanin involve heterogeneous mechanochemical processes and sensitivity of microtubules to Katanin plays significant roles in mitosis/meiosis, neurogenesis, cilia/flagella formation, cell wall development and so on. Deregulated and uncoordinated expression of Katanin has been shown to have implications in pathophysiological conditions. In this paper, we highlight mechanistic models and regulations of microtubule severing by Katanin in context of structure and various functions of Katanin in different organisms.

  9. How does bias correction of regional climate model precipitation affect modelled runoff?

    NASA Astrophysics Data System (ADS)

    Teng, J.; Potter, N. J.; Chiew, F. H. S.; Zhang, L.; Wang, B.; Vaze, J.; Evans, J. P.

    2015-02-01

    Many studies bias correct daily precipitation from climate models to match the observed precipitation statistics, and the bias corrected data are then used for various modelling applications. This paper presents a review of recent methods used to bias correct precipitation from regional climate models (RCMs). The paper then assesses four bias correction methods applied to the weather research and forecasting (WRF) model simulated precipitation, and the follow-on impact on modelled runoff for eight catchments in southeast Australia. Overall, the best results are produced by either quantile mapping or a newly proposed two-state gamma distribution mapping method. However, the differences between the methods are small in the modelling experiments here (and as reported in the literature), mainly due to the substantial corrections required and inconsistent errors over time (non-stationarity). The errors in bias corrected precipitation are typically amplified in modelled runoff. The tested methods cannot overcome limitations of the RCM in simulating precipitation sequence, which affects runoff generation. Results further show that whereas bias correction does not seem to alter change signals in precipitation means, it can introduce additional uncertainty to change signals in high precipitation amounts and, consequently, in runoff. Future climate change impact studies need to take this into account when deciding whether to use raw or bias corrected RCM results. Nevertheless, RCMs will continue to improve and will become increasingly useful for hydrological applications as the bias in RCM simulations reduces.

  10. Modeling the effect of sleep regulation on a neural mass model.

    PubMed

    Costa, Michael Schellenberger; Born, Jan; Claussen, Jens Christian; Martinetz, Thomas

    2016-08-01

    In mammals, sleep is categorized by two main sleep stages, rapid eye movement (REM) and non-REM (NREM) sleep that are known to fulfill different functional roles, the most notable being the consolidation of memory. While REM sleep is characterized by brain activity similar to wakefulness, the EEG activity changes drastically with the emergence of K-complexes, sleep spindles and slow oscillations during NREM sleep. These changes are regulated by circadian and ultradian rhythms, which emerge from an intricate interplay between multiple neuronal populations in the brainstem, forebrain and hypothalamus and the resulting varying levels of neuromodulators. Recently, there has been progress in the understanding of those rhythms both from a physiological as well as theoretical perspective. However, how these neuromodulators affect the generation of the different EEG patterns and their temporal dynamics is poorly understood. Here, we build upon previous work on a neural mass model of the sleeping cortex and investigate the effect of those neuromodulators on the dynamics of the cortex and the corresponding transition between wakefulness and the different sleep stages. We show that our simplified model is sufficient to generate the essential features of human EEG over a full day. This approach builds a bridge between sleep regulatory networks and EEG generating neural mass models and provides a valuable tool for model validation. PMID:27066796

  11. Intentional social distance regulation alters affective responses towards victims of violence: an FMRI study.

    PubMed

    Leiberg, Susanne; Eippert, Falk; Veit, Ralf; Anders, Silke

    2012-10-01

    We used functional magnetic resonance imaging (fMRI) to investigate brain processes underlying control of emotional responses towards a person in distress by cognitive social distance modulation. fMRI and peripheral physiological responses (startle response and electrodermal activity) were recorded from 24 women while they watched victim-offender scenes and modulated their social distance to the victim by cognitive reappraisal. We found that emotional responses, including startle eyeblink and amygdala responses, can effectively be modulated by social distance modulation. Furthermore, our data provide evidence that activity in the dorsomedial prefrontal cortex (dmPFC) and the anterior paracingulate cortex (aPCC), two brain regions that have previously been associated with brain processes related to distant and close others, is differentially modulated by intentional social distance modulation: activity in the dmPFC increased with increasing disengagement from the victim and activity in the aPCC increased with increasing engagement with the victim. We suggest that these two regions play opposing roles in cognitive modulation of social distance and affective responses towards persons in distress that enable the adaptive and flexible social behavior observed in humans. PMID:21998031

  12. Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines

    SciTech Connect

    Maneckjee, R.; Minna, J.D. Uniformed Services Univ. of the Health Sciences, Bethesda, MD )

    1990-05-01

    Using specific radioactively-labeled ligands, the authors find that lung cancer cell lines of diverse histologic types express multiple, high-affinity membrane receptors for {mu}, {delta}, and {kappa} opioid agonists and for nicotine and {alpha}-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas {mu}, {delta}, and {kappa} opioid agonists at low concentrations inhibited lung cancer growth in vitro. They also found that lung cancer cells expressed various combinations of immunoreactive opioid peptides ({beta}-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, they tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a tumor suppressor system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer.

  13. Regulation of electron transfer processes affects phototrophic mat structure and activity.

    PubMed

    Ha, Phuc T; Renslow, Ryan S; Atci, Erhan; Reardon, Patrick N; Lindemann, Stephen R; Fredrickson, James K; Call, Douglas R; Beyenal, Haluk

    2015-01-01

    Phototrophic microbial mats are among the most diverse ecosystems in nature. These systems undergo daily cycles in redox potential caused by variations in light energy input and metabolic interactions among the microbial species. In this work, solid electrodes with controlled potentials were placed under mats to study the electron transfer processes between the electrode and the microbial mat. The phototrophic microbial mat was harvested from Hot Lake, a hypersaline, epsomitic lake located near Oroville (Washington, USA). We operated two reactors: graphite electrodes were polarized at potentials of -700 mVAg/AgCl [cathodic (CAT) mat system] and +300 mVAg/AgCl [anodic (AN) mat system] and the electron transfer rates between the electrode and mat were monitored. We observed a diel cycle of electron transfer rates for both AN and CAT mat systems. Interestingly, the CAT mats generated the highest reducing current at the same time points that the AN mats showed the highest oxidizing current. To characterize the physicochemical factors influencing electron transfer processes, we measured depth profiles of dissolved oxygen (DO) and sulfide in the mats using microelectrodes. We further demonstrated that the mat-to-electrode and electrode-to-mat electron transfer rates were light- and temperature-dependent. Using nuclear magnetic resonance (NMR) imaging, we determined that the electrode potential regulated the diffusivity and porosity of the microbial mats. Both porosity and diffusivity were higher in the CAT mats than in the AN mats. We also used NMR spectroscopy for high-resolution quantitative metabolite analysis and found that the CAT mats had significantly higher concentrations of osmoprotectants such as betaine and trehalose. Subsequently, we performed amplicon sequencing across the V4 region of the 16S rRNA gene of incubated mats to understand the impact of electrode potential on microbial community structure. These data suggested that variation in the

  14. Regulation of electron transfer processes affects phototrophic mat structure and activity

    PubMed Central

    Ha, Phuc T.; Renslow, Ryan S.; Atci, Erhan; Reardon, Patrick N.; Lindemann, Stephen R.; Fredrickson, James K.; Call, Douglas R.; Beyenal, Haluk

    2015-01-01

    Phototrophic microbial mats are among the most diverse ecosystems in nature. These systems undergo daily cycles in redox potential caused by variations in light energy input and metabolic interactions among the microbial species. In this work, solid electrodes with controlled potentials were placed under mats to study the electron transfer processes between the electrode and the microbial mat. The phototrophic microbial mat was harvested from Hot Lake, a hypersaline, epsomitic lake located near Oroville (Washington, USA). We operated two reactors: graphite electrodes were polarized at potentials of -700 mVAg/AgCl [cathodic (CAT) mat system] and +300 mVAg/AgCl [anodic (AN) mat system] and the electron transfer rates between the electrode and mat were monitored. We observed a diel cycle of electron transfer rates for both AN and CAT mat systems. Interestingly, the CAT mats generated the highest reducing current at the same time points that the AN mats showed the highest oxidizing current. To characterize the physicochemical factors influencing electron transfer processes, we measured depth profiles of dissolved oxygen (DO) and sulfide in the mats using microelectrodes. We further demonstrated that the mat-to-electrode and electrode-to-mat electron transfer rates were light- and temperature-dependent. Using nuclear magnetic resonance (NMR) imaging, we determined that the electrode potential regulated the diffusivity and porosity of the microbial mats. Both porosity and diffusivity were higher in the CAT mats than in the AN mats. We also used NMR spectroscopy for high-resolution quantitative metabolite analysis and found that the CAT mats had significantly higher concentrations of osmoprotectants such as betaine and trehalose. Subsequently, we performed amplicon sequencing across the V4 region of the 16S rRNA gene of incubated mats to understand the impact of electrode potential on microbial community structure. These data suggested that variation in the

  15. BAFF regulates T follicular helper cells and affects accumulation and IFNγ production in autoimmunity

    PubMed Central

    Coquery, Christine M.; Loo, William M.; Wade, Nekeithia S.; Bederman, Annelise G.; Tung, Kenneth S.; Lewis, Janet E.; Hess, Henry; Erickson, Loren D.

    2014-01-01

    Objective T follicular helper (TFH) cells are critical for the development of protective antibodies via germinal center (GC) B-cell responses; however, uncontrolled TFH cell expansion activates autoreactive B-cells to produce antibodies that cause autoimmunity. The mechanisms that control TFH cell homeostasis remains largely unknown. The aim of this study was to determine the contribution of BAFF to TFH cell responses in autoimmunity. Methods We analyzed the properties of TFH cells in lupus-prone mice, sufficient or deficient in B-cell maturation antigen (BCMA). Adoptive transfer studies and mixed bone marrow chimeras were used to test BCMA signaling in T cells. We assessed BAFF stimulation of TFH cells through in vitro cell cocultures and in vivo depletion studies using flow cytometry. Results In Nba2 mice, TFH cells expressed the BAFF receptors BCMA and BR3, and accumulated in the spleen when BCMA was absent. BCMA deficiency in T cells promoted the expansion of TFH cells, GC formation, autoantibody production, and IFNγ production by TFH cells through BR3. IFNγ-producing TFH cells increased BAFF expression in dendritic cells. Blocking BAFF or IFNγ in vivo reduced TFH cell accumulation and improved autoimmunity in BCMA-deficient animals. Moreover, circulating TFH-like cells that expressed BR3 (but not BCMA) were elevated in SLE patients, which correlated with serum BAFF and IFNγ titers. Conclusion In Nba2 mice, BCMA negatively regulates TFH cell expansion whereas BAFF signaling through BR3 promotes TFH cell accumulation. Our work suggests the balance between BCMA and BR3 signaling in TFH cells serves as a checkpoint of immune tolerance. PMID:25385309

  16. Hawaii Integrated Energy Assessment. Volume V. Rules, regulations, permits and policies affecting the development of alternate energy sources in Hawaii

    SciTech Connect

    Not Available

    1980-01-01

    A comprehensive presentaton of the major permits, regulations, rules, and controls which are likely to affect the development of alternate energy sources in Hawaii is presented. An overview of the permit process, showing the major categories and types of permits and controls for energy alternatives is presented. This is followed by a brief resume of current and projected changes designed to streamline the permit process. The permits, laws, regulations, and controls that are applicable to the development of energy alternatives in Hawaii are described. The alternate energy technologies affected, a description of the permit or control, and the requirements for conformance are presented for each applicable permit. Federal, state, and county permits and controls are covered. The individual energy technologies being considered as alternatives to the State's present dependence on imported fossil fuels are emphasized. The alternate energy sources covered are bioconversion, geothermal, ocean thermal, wind, solar (direct), and solid waste. For each energy alternative, the significant permits are summarized with a brief explanation of why they may be necessary. The framework of policy development at each of the levels of government with respect to the alternate energy sources is covered.

  17. Complexity Theory: Inclusion of the Affective Domain in an Interactive Learning Model for Instructional Design.

    ERIC Educational Resources Information Center

    Tennyson, Robert D.; Nielsen, Milt

    1998-01-01

    Proposes an interactive learning model to serve as a psychological foundation for the field of instructional design theory. Topics include complexity theory, cognitive models of learning, cognitive and affective domains, sensory receptors component (memory) and the effects of external stimuli, affects component, cognitive strategies, and knowledge…

  18. Introducing an Intervention Model for Fostering Affective Involvement with Persons Who Are Congenitally Deafblind

    ERIC Educational Resources Information Center

    Martens, Marga A. W.; Janssen, Marleen J.; Ruijssenaars, Wied A. J. J. M.; Riksen-Walraven, J. Marianne

    2014-01-01

    The article presented here introduces the Intervention Model for Affective Involvement (IMAI), which was designed to train staff members (for example, teachers, caregivers, support workers) to foster affective involvement during interaction and communication with persons who have congenital deaf-blindness. The model is theoretically underpinned,…

  19. Plasmon-pole models affect band gaps in GW calculations

    NASA Astrophysics Data System (ADS)

    Larson, Paul; Wu, Zhigang

    2013-03-01

    Density functional theory calculations have long been known to underestimate the band gaps in semiconductors. Significant improvements have been made by using GW calculations that uses the self energy, defined as the product of the Green function (G) and screened Coulomb exchange (W). However, many approximations are made in the GW method, specifically the plasmon-pole approximation. This approximation replaces the integration necessary to produce W with a simple approximation to the inverse dielectric function. Four different plasmon-pole approximations have been tested using the tight-binding program ABINIT: Godby-Needs, Hybertsen-Louie, von der Linden-Horsch, and Engel-Farid. For many materials, the differences in the GW band gaps for the different plasmon-pole models are negligible, but for systems with localized electrons, the difference can be larger than 1 eV. The plasmon-pole approximation is generally chosen to best agree with experimental data, but this is misleading in that this ignores all of the other approximations used in the GW method. Improvements in plasmon-pole models in GW can only come about by trying to reproduce the results of the numerical integration rather than trying to reproduce experimental results.

  20. Regulation of electron transfer processes affects phototrophic mat structure and activity

    SciTech Connect

    Ha, Phuc T.; Renslow, Ryan S.; Atci, Erhan; Reardon, Patrick N.; Lindemann, Stephen R.; Fredrickson, James K.; Call, Douglas R.; Beyenal, Haluk

    2015-09-03

    Phototrophic microbial mats are among the most diverse ecosystems in nature. These systems undergo daily cycles in redox potential caused by variations in light energy input and metabolic interactions among the microbial species. In this work, solid electrodes with controlled potentials were placed under mats to study the electron transfer processes between the electrode and the microbial mat. The phototrophic microbial mat was harvested from Hot Lake, a hypersaline, epsomitic lake located near Oroville (Washington, USA). We operated two reactors: graphite electrodes were polarized at potentials of -700 mVAg/AgCl [cathodic (CAT) mat system] and +300 mVAg/AgCl [anodic (AN) mat system] and the electron transfer rates between the electrode and mat were monitored. We observed a diel cycle of electron transfer rates for both AN and CAT mat systems. Interestingly, the CAT mats generated the highest reducing current at the same time points that the AN mats showed the highest oxidizing current. To characterize the physicochemical factors influencing electron transfer processes, we measured depth profiles of dissolved oxygen (DO) and sulfide in the mats using microelectrodes. We further demonstrated that the mat-to-electrode and electrode-to-mat electron transfer rates were light- and temperature-dependent. Using nuclear magnetic resonance (NMR) imaging, we determined that the electrode potential regulated the diffusivity and porosity of the microbial mats. Both porosity and diffusivity were higher in the CAT mats than in the AN mats. We also used NMR spectroscopy for high-resolution quantitative metabolite analysis and found that the CAT mats had significantly higher concentrations of osmoprotectants such as betaine and trehalose. Subsequently, we performed amplicon sequencing across the V4 region of the 16S rRNA gene of incubated mats to understand the impact of electrode potential on microbial community structure. In conclusion, these data suggested

  1. Regulation of electron transfer processes affects phototrophic mat structure and activity

    DOE PAGESBeta

    Ha, Phuc T.; Renslow, Ryan S.; Atci, Erhan; Reardon, Patrick N.; Lindemann, Stephen R.; Fredrickson, James K.; Call, Douglas R.; Beyenal, Haluk

    2015-09-03

    Phototrophic microbial mats are among the most diverse ecosystems in nature. These systems undergo daily cycles in redox potential caused by variations in light energy input and metabolic interactions among the microbial species. In this work, solid electrodes with controlled potentials were placed under mats to study the electron transfer processes between the electrode and the microbial mat. The phototrophic microbial mat was harvested from Hot Lake, a hypersaline, epsomitic lake located near Oroville (Washington, USA). We operated two reactors: graphite electrodes were polarized at potentials of -700 mVAg/AgCl [cathodic (CAT) mat system] and +300 mVAg/AgCl [anodic (AN) mat system]more » and the electron transfer rates between the electrode and mat were monitored. We observed a diel cycle of electron transfer rates for both AN and CAT mat systems. Interestingly, the CAT mats generated the highest reducing current at the same time points that the AN mats showed the highest oxidizing current. To characterize the physicochemical factors influencing electron transfer processes, we measured depth profiles of dissolved oxygen (DO) and sulfide in the mats using microelectrodes. We further demonstrated that the mat-to-electrode and electrode-to-mat electron transfer rates were light- and temperature-dependent. Using nuclear magnetic resonance (NMR) imaging, we determined that the electrode potential regulated the diffusivity and porosity of the microbial mats. Both porosity and diffusivity were higher in the CAT mats than in the AN mats. We also used NMR spectroscopy for high-resolution quantitative metabolite analysis and found that the CAT mats had significantly higher concentrations of osmoprotectants such as betaine and trehalose. Subsequently, we performed amplicon sequencing across the V4 region of the 16S rRNA gene of incubated mats to understand the impact of electrode potential on microbial community structure. In conclusion, these data suggested that

  2. Self-Regulated Learning (SRL): Emergence of the RSRLM Model

    ERIC Educational Resources Information Center

    Nodoushan, Mohammad Ali Salmani

    2012-01-01

    This paper claims that the current theories of Self-regulated learning (SRL) are short-sighted. The author provides a comprehensive, but brief, overview of SRL which addresses such issues as (a) SRL processes, (b) SRL strategies, (c) compartments of SRL, (d) theories of SRL, (e) agency in SRL, and (f) models of SRL. He then presents a new model…

  3. Acute Lipotoxicity Regulates Severity of Biliary Acute Pancreatitis without Affecting Its Initiation

    PubMed Central

    Durgampudi, Chandra; Noel, Pawan; Patel, Krutika; Cline, Rachel; Trivedi, Ram N.; DeLany, James P.; Yadav, Dhiraj; Papachristou, Georgios I.; Lee, Kenneth; Acharya, Chathur; Jaligama, Deepthi; Navina, Sarah; Murad, Faris; Singh, Vijay P.

    2015-01-01

    Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O–positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate–induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction. PMID:24854864

  4. Considering an Affect Regulation Framework for Examining the Association Between Body Dissatisfaction and Positive Body Image in Black Older Adolescent Females: Does Body Mass Index Matter?

    PubMed Central

    Butler-Ajibade, Phoebe; Robinson, Seronda A.

    2014-01-01

    The present study provided an initial evaluation of an affect regulation model describing the association between body dissatisfaction and two contemporary measures of positive body image among 247 Black college-bound older adolescent females. We further tested whether possessing a higher body mass index (BMI) would strengthen these associations. Self-reported height and weight were used to calculate BMI. Respondents also completed a culturally-sensitive figure rating scale along with assessments of body appreciation and body image flexibility. Results indicated a robust positive association between the two measures of positive body image; BMI was the strongest predictor of both body appreciation and body image flexibility with body size discrepancy (current minus ideal) contributing incremental variance to both models tested. Implications for improving our understanding of the association between positive and negative body image and bolstering positive body image to promote health-protective behaviors among Black young women at this developmental juncture are discussed. PMID:25079011

  5. Up-regulation of LSB1/GDU3 affects geminivirus infection by activating the salicylic acid pathway.

    PubMed

    Chen, Hao; Zhang, Zhonghui; Teng, Kunling; Lai, Jianbin; Zhang, Yiyue; Huang, Yiliang; Li, Yin; Liang, Liming; Wang, Yiqin; Chu, Chengcai; Guo, Huishan; Xie, Qi

    2010-04-01

    Geminiviruses include a large number of single-stranded DNA viruses that are emerging as useful tools to dissect many fundamental processes in plant hosts. However, there have been no reports yet regarding the genetic dissection of the geminivirus-plant interaction. Here, a high-throughput approach was developed to screen Arabidopsis activation-tagged mutants which are resistant to geminivirus Beet severe curly top virus (BSCTV) infection. A mutant, lsb1 (less susceptible to BSCTV 1), was identified, in which BSCTV replication was impaired and BSCTV infectivity was reduced. We found that the three genes closest to the T-DNA were up-regulated in lsb1, and the phenotypes of lsb1 could only be recapitulated by the overexpression of GDU3 (GLUTAMINE DUMPER 3), a gene implicated in amino acid transport. We further demonstrated that activation of LSB1/GDU3 increased the expression of components in the salicylic acid (SA) pathway, which is known to counter geminivirus infection, including the upstream regulator ACD6. These data indicate that up-regulation of LSB1/GDU3 affects BSCTV infection by activating the SA pathway. This study thus provides a new approach to study of the geminivirus-host interaction. PMID:20042021

  6. Re-Evaluating Neonatal-Age Models for Ungulates: Does Model Choice Affect Survival Estimates?

    PubMed Central

    Grovenburg, Troy W.; Monteith, Kevin L.; Jacques, Christopher N.; Klaver, Robert W.; DePerno, Christopher S.; Brinkman, Todd J.; Monteith, Kyle B.; Gilbert, Sophie L.; Smith, Joshua B.; Bleich, Vernon C.; Swanson, Christopher C.; Jenks, Jonathan A.

    2014-01-01

    New-hoof growth is regarded as the most reliable metric for predicting age of newborn ungulates, but variation in estimated age among hoof-growth equations that have been developed may affect estimates of survival in staggered-entry models. We used known-age newborns to evaluate variation in age estimates among existing hoof-growth equations and to determine the consequences of that variation on survival estimates. During 2001–2009, we captured and radiocollared 174 newborn (≤24-hrs old) ungulates: 76 white-tailed deer (Odocoileus virginianus) in Minnesota and South Dakota, 61 mule deer (O. hemionus) in California, and 37 pronghorn (Antilocapra americana) in South Dakota. Estimated age of known-age newborns differed among hoof-growth models and varied by >15 days for white-tailed deer, >20 days for mule deer, and >10 days for pronghorn. Accuracy (i.e., the proportion of neonates assigned to the correct age) in aging newborns using published equations ranged from 0.0% to 39.4% in white-tailed deer, 0.0% to 3.3% in mule deer, and was 0.0% for pronghorns. Results of survival modeling indicated that variability in estimates of age-at-capture affected short-term estimates of survival (i.e., 30 days) for white-tailed deer and mule deer, and survival estimates over a longer time frame (i.e., 120 days) for mule deer. Conversely, survival estimates for pronghorn were not affected by estimates of age. Our analyses indicate that modeling survival in daily intervals is too fine a temporal scale when age-at-capture is unknown given the potential inaccuracies among equations used to estimate age of neonates. Instead, weekly survival intervals are more appropriate because most models accurately predicted ages within 1 week of the known age. Variation among results of neonatal-age models on short- and long-term estimates of survival for known-age young emphasizes the importance of selecting an appropriate hoof-growth equation and appropriately defining intervals (i.e., weekly

  7. Re-evaluating neonatal-age models for ungulates: Does model choice affect survival estimates?

    USGS Publications Warehouse

    Grovenburg, Troy W.; Monteith, Kevin L.; Jacques, Christopher N.; Klaver, Robert W.; DePerno, Christopher S.; Brinkman, Todd J.; Monteith, Kyle B.; Gilbert, Sophie L.; Smith, Joshua B.; Bleich, Vernon C.; Swanson, Christopher C.; Jenks, Jonathan A.

    2014-01-01

    New-hoof growth is regarded as the most reliable metric for predicting age of newborn ungulates, but variation in estimated age among hoof-growth equations that have been developed may affect estimates of survival in staggered-entry models. We used known-age newborns to evaluate variation in age estimates among existing hoof-growth equations and to determine the consequences of that variation on survival estimates. During 2001–2009, we captured and radiocollared 174 newborn (≤24-hrs old) ungulates: 76 white-tailed deer (Odocoileus virginianus) in Minnesota and South Dakota, 61 mule deer (O. hemionus) in California, and 37 pronghorn (Antilocapra americana) in South Dakota. Estimated age of known-age newborns differed among hoof-growth models and varied by >15 days for white-tailed deer, >20 days for mule deer, and >10 days for pronghorn. Accuracy (i.e., the proportion of neonates assigned to the correct age) in aging newborns using published equations ranged from 0.0% to 39.4% in white-tailed deer, 0.0% to 3.3% in mule deer, and was 0.0% for pronghorns. Results of survival modeling indicated that variability in estimates of age-at-capture affected short-term estimates of survival (i.e., 30 days) for white-tailed deer and mule deer, and survival estimates over a longer time frame (i.e., 120 days) for mule deer. Conversely, survival estimates for pronghorn were not affected by estimates of age. Our analyses indicate that modeling survival in daily intervals is too fine a temporal scale when age-at-capture is unknown given the potential inaccuracies among equations used to estimate age of neonates. Instead, weekly survival intervals are more appropriate because most models accurately predicted ages within 1 week of the known age. Variation among results of neonatal-age models on short- and long-term estimates of survival for known-age young emphasizes the importance of selecting an appropriate hoof-growth equation and appropriately defining intervals (i.e., weekly

  8. Does Changing Atmospheric Model Resolution Affect Atmospheric Feedbacks?

    NASA Astrophysics Data System (ADS)

    Tett, S. F.; Wehner, M. F.; Stone, D. A.

    2014-12-01

    Simulations of the Community Atmosphere Model version 5.1 (CAM5.1) at horizontal resolutions of approximately 2, 1 and 0.25 degrees driven with climatological sea surface temperatures (SST) and 1990 forcings were carried out. The 1 and 2 degree CAM5.1 configurations used the default parameter values with the 0.25 degree CAM5.1 using the 1 degree configuration except the physics timestep being halved. Perturbed experiments, using CAM5.1, in which either SST is uniformly increased by 2K or CO2 doubled werealso carried out using the same configurations. A ``Cess'' type feedback analysis (twice change in 2xCO2/change in 2K simulations) was used to diagnose a ``Cess'' sensitivity. This sensitivity increased slightly with resolution due to changes in both the response to the uniform SST increase and to doubling CO2. This appears to arise from differing changes in tropical cloudsas resolution increases. Our results suggest that uncertainty in climate sensitivity is not strongly impacted by changing horizontal resolution up to 25 km. Thus, uncertainty in parameterisation likely remain the leading source of uncertainty in climate sensitivity.

  9. Commentary: issues and perspectives affecting CRNA practice. Regulation of health professionals, Part 1: Telepractice.

    PubMed

    Gunn, I P

    1999-05-01

    Although the requirement to protect the public welfare and safety is a right guaranteed to the states by the US Constitution's 10th amendment, which grants states the "police powers" of government, it is not an absolute power. The Commerce clause of the Constitution limits the power of states in creating barriers to intrastate commerce. Changes in the health care delivery system of the US, such as the use of corporate models such as managed care entities and health maintenance organizations, as well as health insurers' development of utilization reviews before approval of reimbursable procedures in individual cases, has prompted concerns with regard to the care of patients occurring outside the state in which the patient resides, by health care professionals not licensed in that state. Many states have considered such decision making an "unauthorized practice of medicine, or other practice" creating the necessity for some providers to obtain an many as 20 licenses to cover their practice. The practice of telemedicine (or telenursing or telehealth) falls into this quagmire, and thus efforts are ongoing to try to find ways to permit such practices while maintaining quality control, with or without additional state licenses. PMID:10504915

  10. Integrating Learning Styles and Personality Traits into an Affective Model to Support Learner's Learning

    NASA Astrophysics Data System (ADS)

    Leontidis, Makis; Halatsis, Constantin

    The aim of this paper is to present a model in order to integrate the learning style and the personality traits of a learner into an enhanced Affective Style which is stored in the learner’s model. This model which can deal with the cognitive abilities as well as the affective preferences of the learner is called Learner Affective Model (LAM). The LAM is used to retain learner’s knowledge and activities during his interaction with a Web-based learning environment and also to provide him with the appropriate pedagogical guidance. The proposed model makes use of an ontological approach in combination with the Bayesian Network model and contributes to the efficient management of the LAM in an Affective Module.

  11. Modelling, property verification and behavioural equivalence of lactose operon regulation.

    PubMed

    Pinto, Marcelo Cezar; Foss, Luciana; Mombach, José Carlos Merino; Ribeiro, Leila

    2007-02-01

    Understanding biochemical pathways is one of the biggest challenges in the field of molecular biology nowadays. Computer science can contribute in this area by providing formalisms and tools to simulate and analyse pathways. One formalism that is suited for modelling concurrent systems is Milner's Calculus of Communicating Systems (CCS). This paper shows the viability of using CCS to model and reason about biochemical networks. As a case study, we describe the regulation of lactose operon. After describing this operon formally using CCS, we validate our model by automatically checking some known properties for lactose regulation. Moreover, since biological systems tend to be very complex, we propose to use multiple descriptions of the same system at different levels of abstraction. The compatibility of these multiple views can be assured via mathematical proofs of observational equivalence. PMID:16620804

  12. Bang-bang Model for Regulation of Local Blood Flow

    PubMed Central

    Golub, Aleksander S.; Pittman, Roland N.

    2013-01-01

    The classical model of metabolic regulation of blood flow in muscle tissue implies the maintenance of basal tone in arterioles of resting muscle and their dilation in response to exercise and/or tissue hypoxia via the evoked production of vasodilator metabolites by myocytes. A century-long effort to identify specific metabolites responsible for explaining active and reactive hyperemia has not been successful. Furthermore, the metabolic theory is not compatible with new knowledge on the role of physiological radicals (e.g., nitric oxide, NO, and superoxide anion, O2−) in the regulation of microvascular tone. We propose a model of regulation in which muscle contraction and active hyperemia are considered the physiologically normal state. We employ the “bang-bang” or “on/off” regulatory model which makes use of a threshold and hysteresis; a float valve to control the water level in a tank is a common example of this type of regulation. Active bang-bang regulation comes into effect when the supply of oxygen and glucose exceeds the demand, leading to activation of membrane NADPH oxidase, release of O2− into the interstitial space and subsequent neutralization of the interstitial NO. Switching arterioles on/off when local blood flow crosses the threshold is realized by a local cell circuit with the properties of a bang-bang controller, determined by its threshold, hysteresis and dead-band. This model provides a clear and unambiguous interpretation of the mechanism to balance tissue demand with a sufficient supply of nutrients and oxygen. PMID:23441827

  13. Identification and synthetic modeling of factors affecting American black duck populations

    USGS Publications Warehouse

    Conroy, Michael J.; Miller, Mark W.; Hines, James E.

    2002-01-01

    We reviewed the literature on factors potentially affecting the population status of American black ducks (Anas rupribes). Our review suggests that there is some support for the influence of 4 major, continental-scope factors in limiting or regulating black duck populations: 1) loss in the quantity or quality of breeding habitats; 2) loss in the quantity or quality of wintering habitats; 3) harvest, and 4) interactions (competition, hybridization) with mallards (Anas platyrhychos) during the breeding and/or wintering periods. These factors were used as the basis of an annual life cycle model in which reproduction rates and survival rates were modeled as functions of the above factors, with parameters of the model describing the strength of these relationships. Variation in the model parameter values allows for consideration of scientific uncertainty as to the degree each of these factors may be contributing to declines in black duck populations, and thus allows for the investigation of the possible effects of management (e.g., habitat improvement, harvest reductions) under different assumptions. We then used available, historical data on black duck populations (abundance, annual reproduction rates, and survival rates) and possible driving factors (trends in breeding and wintering habitats, harvest rates, and abundance of mallards) to estimate model parameters. Our estimated reproduction submodel included parameters describing negative density feedback of black ducks, positive influence of breeding habitat, and negative influence of mallard densities; our survival submodel included terms for positive influence of winter habitat on reproduction rates, and negative influences of black duck density (i.e., compensation to harvest mortality). Individual models within each group (reproduction, survival) involved various combinations of these factors, and each was given an information theoretic weight for use in subsequent prediction. The reproduction model with highest

  14. Implementation of a model of bodily fluids regulation.

    PubMed

    Fontecave-Jallon, Julie; Thomas, S Randall

    2015-09-01

    The classic model of blood pressure regulation by Guyton et al. (Annu Rev Physiol 34:13-46, 1972a; Ann Biomed Eng 1:254-281, 1972b) set a new standard for quantitative exploration of physiological function and led to important new insights, some of which still remain the focus of debate, such as whether the kidney plays the primary role in the genesis of hypertension (Montani et al. in Exp Physiol 24:41-54, 2009a; Exp Physiol 94:382-388, 2009b; Osborn et al. in Exp Physiol 94:389-396, 2009a; Exp Physiol 94:388-389, 2009b). Key to the success of this model was the fact that the authors made the computer code (in FORTRAN) freely available and eventually provided a convivial user interface for exploration of model behavior on early microcomputers (Montani et al. in Int J Bio-med Comput 24:41-54, 1989). Ikeda et al. (Ann Biomed Eng 7:135-166, 1979) developed an offshoot of the Guyton model targeting especially the regulation of body fluids and acid-base balance; their model provides extended renal and respiratory functions and would be a good basis for further extensions. In the interest of providing a simple, useable version of Ikeda et al.'s model and to facilitate further such extensions, we present a practical implementation of the model of Ikeda et al. (Ann Biomed Eng 7:135-166, 1979), using the ODE solver Berkeley Madonna. PMID:25935135

  15. Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism.

    PubMed

    Andreoli, María Florencia; Stoker, Cora; Rossetti, María Florencia; Alzamendi, Ana; Castrogiovanni, Daniel; Luque, Enrique H; Ramos, Jorge Guillermo

    2015-02-01

    The absence of phytoestrogens in the diet during pregnancy has been reported to result in obesity later in adulthood. We investigated whether phytoestrogen withdrawal in adult life could alter the hypothalamic signals that regulate food intake and affect body weight and glucose homeostasis. Male Wistar rats fed from conception to adulthood with a high phytoestrogen diet were submitted to phytoestrogen withdrawal by feeding a low phytoestrogen diet, or a high phytoestrogen-high fat diet. Withdrawal of dietary phytoestrogens increased body weight, adiposity and energy intake through an orexigenic hypothalamic response characterized by upregulation of AGRP and downregulation of POMC. This was associated with elevated leptin and T4, reduced TSH, testosterone and estradiol, and diminished hypothalamic ERα expression, concomitant with alterations in glucose tolerance. Removing dietary phytoestrogens caused manifestations of obesity and diabetes that were more pronounced than those induced by the high phytoestrogen-high fat diet intake. PMID:25486512

  16. Power training and postmenopausal hormone therapy affect transcriptional control of specific co-regulated gene clusters in skeletal muscle

    PubMed Central

    Fey, Vidal; Törmäkangas, Timo; Ronkainen, Paula H. A.; Taaffe, Dennis R.; Takala, Timo; Koskinen, Satu; Cheng, Sulin; Puolakka, Jukka; Kujala, Urho M.; Suominen, Harri; Sipilä, Sarianna; Kovanen, Vuokko

    2010-01-01

    At the moment, there is no clear molecular explanation for the steeper decline in muscle performance after menopause or the mechanisms of counteractive treatments. The goal of this genome-wide study was to identify the genes and gene clusters through which power training (PT) comprising jumping activities or estrogen containing hormone replacement therapy (HRT) may affect skeletal muscle properties after menopause. We used musculus vastus lateralis samples from early stage postmenopausal (50–57 years old) women participating in a yearlong randomized double-blind placebo-controlled trial with PT and HRT interventions. Using microarray platform with over 24,000 probes, we identified 665 differentially expressed genes. The hierarchical clustering method was used to assort the genes. Additionally, enrichment analysis of gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was carried out to clarify whether assorted gene clusters are enriched with particular functional categories. The analysis revealed transcriptional regulation of 49 GO/KEGG categories. PT upregulated transcription in “response to contraction”—category revealing novel candidate genes for contraction-related regulation of muscle function while HRT upregulated gene expression related to functionality of mitochondria. Moreover, several functional categories tightly related to muscle energy metabolism, development, and function were affected regardless of the treatment. Our results emphasize that during the early stages of the postmenopause, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle power and potentially reducing the risk for aging-related muscle weakness. More specifically, PT and HRT may function through improving energy metabolism, response to contraction as well as by preserving functionality of the mitochondria. Electronic supplementary material The online version of this

  17. Seasonal Dynamics of Trace Elements in Tidal Salt Marsh Soils as Affected by the Flow-Sediment Regulation Regime

    PubMed Central

    Bai, Junhong; Xiao, Rong; Zhao, Qingqing; Lu, Qiongqiong; Wang, Junjing; Reddy, K. Ramesh

    2014-01-01

    Soil profiles were collected in three salt marshes with different plant species (i.e. Phragmites australis, Tamarix chinensis and Suaeda salsa) in the Yellow River Delta (YRD) of China during three seasons (summer and fall of 2007 and the following spring of 2008) after the flow-sediment regulation regime. Total elemental contents of As, Cd, Cu, Pb and Zn were determined using inductively coupled plasma atomic absorption spectrometry to investigate temporal variations in trace elements in soil profiles of the three salt marshes, assess the enrichment levels and ecological risks of these trace elements in three sampling seasons and identify their influencing factors. Trace elements did not change significantly along soil profiles at each site in each sampling season. The highest value for each sampling site was observed in summer and the lowest one in fall. Soils in both P. australis and S. salsa wetlands tended to have higher trace element levels than those in T. chinensis wetland. Compared to other elements, both Cd and As had higher enrichment factors exceeding moderate enrichment levels. However, the toxic unit (TU) values of these trace elements did not exceed probable effect levels. Correlation analysis showed that these trace elements were closely linked to soil properties such as moisture, sulfur, salinity, soil organic matter, soil texture and pH values. Principal component analysis showed that the sampling season affected by the flow-sediment regulation regime was the dominant factor influencing the distribution patterns of these trace elements in soils, and plant community type was another important factor. The findings of this study could contribute to wetland conservation and management in coastal regions affected by the hydrological engineering. PMID:25216278

  18. Heat Shock Protein 70.1 (Hsp70.1) Affects Neuronal Cell Fate by Regulating Lysosomal Acid Sphingomyelinase*

    PubMed Central

    Zhu, Hong; Yoshimoto, Tanihiro; Yamashima, Tetsumori

    2014-01-01

    The inducible expression of heat shock protein 70.1 (Hsp70.1) plays cytoprotective roles in its molecular chaperone function. Binding of Hsp70 to an endolysosomal phospholipid, bis(monoacylglycero)phosphate (BMP), has been recently shown to stabilize lysosomal membranes by enhancing acid sphingomyelinase (ASM) activity in cancer cells. Using the monkey experimental paradigm, we have reported that calpain-mediated cleavage of oxidized Hsp70.1 causes neurodegeneration in the hippocampal cornu ammonis 1 (CA1), whereas expression of Hsp70.1 in the motor cortex without calpain activation contributes to neuroprotection. However, the molecular mechanisms of the lysosomal destabilization/stabilization determining neuronal cell fate have not been elucidated. To elucidate whether regulation of lysosomal ASM could affect the neuronal fate, we analyzed Hsp70.1-BMP binding and ASM activity by comparing the motor cortex and the CA1. We show that Hsp70.1 being localized at the lysosomal membrane, lysosomal lipid BMP levels, and the lipid binding domain of Hsp70.1 are crucial for Hsp70.1-BMP binding. In the postischemic motor cortex, Hsp70.1 being localized at the lysosomal membrane could bind to BMP without calpain activation and decreased BMP levels, resulting in increasing ASM activity and lysosomal stability. However, in the postischemic CA1, calpain activation and a concomitant decrease in the lysosomal membrane localization of Hsp70.1 and BMP levels may diminish Hsp70.1-BMP binding, resulting in decreased ASM activity and lysosomal rupture with leakage of cathepsin B into the cytosol. A TUNEL assay revealed the differential neuronal vulnerability between the CA1 and the motor cortex. These results suggest that regulation of ASM activation in vivo by Hsp70.1-BMP affects lysosomal stability and neuronal survival or death after ischemia/reperfusion. PMID:25074941

  19. One-Class FMRI-Inspired EEG Model for Self-Regulation Training.

    PubMed

    Meir-Hasson, Yehudit; Keynan, Jackob N; Kinreich, Sivan; Jackont, Gilan; Cohen, Avihay; Podlipsky-Klovatch, Ilana; Hendler, Talma; Intrator, Nathan

    2016-01-01

    Recent evidence suggests that learned self-regulation of localized brain activity in deep limbic areas such as the amygdala, may alleviate symptoms of affective disturbances. Thus far self-regulation of amygdala activity could be obtained only via fMRI guided neurofeedback, an expensive and immobile procedure. EEG on the other hand is relatively inexpensive and can be easily implemented in any location. However the clinical utility of EEG neurofeedback for affective disturbances remains limited due to low spatial resolution, which hampers the targeting of deep limbic areas such as the amygdala. We introduce an EEG prediction model of amygdala activity from a single electrode. The gold standard used for training is the fMRI-BOLD signal in the amygdala during simultaneous EEG/fMRI recording. The suggested model is based on a time/frequency representation of the EEG data with varying time-delay. Previous work has shown a strong inhomogeneity among subjects as is reflected by the models created to predict the amygdala BOLD response from EEG data. In that work, different models were constructed for different subjects. In this work, we carefully analyzed the inhomogeneity among subjects and were able to construct a single model for the majority of the subjects. We introduce a method for inhomogeneity assessment. This enables us to demonstrate a choice of subjects for which a single model could be derived. We further demonstrate the ability to modulate brain-activity in a neurofeedback setting using feedback generated by the model. We tested the effect of the neurofeedback training by showing that new subjects can learn to down-regulate the signal amplitude compared to a sham group, which received a feedback obtained by a different participant. This EEG based model can overcome substantial limitations of fMRI-NF. It can enable investigation of NF training using multiple sessions and large samples in various locations. PMID:27163677

  20. One-Class FMRI-Inspired EEG Model for Self-Regulation Training

    PubMed Central

    Kinreich, Sivan; Jackont, Gilan; Cohen, Avihay; Podlipsky-Klovatch, Ilana; Hendler, Talma; Intrator, Nathan

    2016-01-01

    Recent evidence suggests that learned self-regulation of localized brain activity in deep limbic areas such as the amygdala, may alleviate symptoms of affective disturbances. Thus far self-regulation of amygdala activity could be obtained only via fMRI guided neurofeedback, an expensive and immobile procedure. EEG on the other hand is relatively inexpensive and can be easily implemented in any location. However the clinical utility of EEG neurofeedback for affective disturbances remains limited due to low spatial resolution, which hampers the targeting of deep limbic areas such as the amygdala. We introduce an EEG prediction model of amygdala activity from a single electrode. The gold standard used for training is the fMRI-BOLD signal in the amygdala during simultaneous EEG/fMRI recording. The suggested model is based on a time/frequency representation of the EEG data with varying time-delay. Previous work has shown a strong inhomogeneity among subjects as is reflected by the models created to predict the amygdala BOLD response from EEG data. In that work, different models were constructed for different subjects. In this work, we carefully analyzed the inhomogeneity among subjects and were able to construct a single model for the majority of the subjects. We introduce a method for inhomogeneity assessment. This enables us to demonstrate a choice of subjects for which a single model could be derived. We further demonstrate the ability to modulate brain-activity in a neurofeedback setting using feedback generated by the model. We tested the effect of the neurofeedback training by showing that new subjects can learn to down-regulate the signal amplitude compared to a sham group, which received a feedback obtained by a different participant. This EEG based model can overcome substantial limitations of fMRI-NF. It can enable investigation of NF training using multiple sessions and large samples in various locations. PMID:27163677

  1. Sleep and affect in older adults: using multilevel modeling to examine daily associations

    PubMed Central

    McCRAE, CHRISTINA S.; McNAMARA, JOSEPH P. H.; ROWE, MEREDETH A.; DZIERZEWSKI, JOSEPH M.; DIRK, JUDITH; MARSISKE, MICHAEL; CRAGGS, JASON G.

    2010-01-01

    SUMMARY The main objective of the present study was to examine daily associations (intraindividual variability or IIV) between sleep and affect in older adults. Greater understanding of these associations is important, because both sleep and affect represent modifiable behaviors that can have a major influence on older adults’ health and well-being. We collected sleep diaries, actigraphy, and affect data concurrently for 14 days in 103 community-dwelling older adults. Multilevel modeling was used to assess the sleep–affect relationship at both the group (between-persons) and individual (within-person or IIV) levels. We hypothesized that nights characterized by better sleep would be associated with days characterized by higher positive affect and lower negative affect, and that the inverse would be true for poor sleep. Daily associations were found between affect and subjective sleep, only and were in the hypothesized direction. Specifically, nights with greater reported awake time or lower sleep quality ratings were associated with days characterized by less positive affect and more negative affect. Gender was not a significant main effect in the present study, despite previous research suggesting gender differences in the sleep–affect relationship. The fact that self-ratings of sleep emerged as the best predictors of affect may suggest that perceived sleep is a particularly important predictor. Finally, our results suggest exploration of affect as a potential intervention target in late-life insomnia is warranted. PMID:18275554

  2. Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules.

    PubMed

    Tikka, Saara; Monogioudi, Evanthia; Gotsopoulos, Athanasios; Soliymani, Rabah; Pezzini, Francesco; Scifo, Enzo; Uusi-Rauva, Kristiina; Tyynelä, Jaana; Baumann, Marc; Jalanko, Anu; Simonati, Alessandro; Lalowski, Maciej

    2016-03-01

    Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced. For this purpose, we utilized a combination of laser capture microdissection-based quantitative liquid chromatography tandem mass spectrometry (MS) and matrix-assisted laser desorption/ionization time-of-flight MS imaging to quantify/visualize the changes in protein expression in disease-affected brain thalamus and cerebral cortex tissue slices, respectively. Proteomic profiling of the pre-symptomatic stage thalamus revealed alterations mostly in metabolic processes and inhibition of various neuronal functions, i.e., neuritogenesis. Down-regulation in dynamics associated with growth of plasma projections and cellular protrusions was further corroborated by findings from RNA sequencing of CLN1 patients' fibroblasts. Changes detected at the symptomatic stage included: mitochondrial functions, synaptic vesicle transport, myelin proteome and signaling cascades, such as RhoA signaling. Considerable dysregulation of processes related to mitochondrial cell death, RhoA/Huntington's disease signaling and myelin sheath breakdown were observed at the advanced stage of the disease. The identified changes in protein levels were further substantiated by bioinformatics and network approaches, immunohistochemistry on brain tissues and literature knowledge, thus identifying various functional modules affected in the CLN1 childhood

  3. Interactions Between the Prefrontal Cortex and Attentional Systems During Volitional Affective Regulation: An Effective Connectivity Reappraisal Study.

    PubMed

    Ligeza, Tomasz S; Wyczesany, Miroslaw; Tymorek, Agnieszka D; Kamiński, Maciej

    2016-03-01

    Reappraisal is an emotion regulation strategy used to change reactions to emotion-related stimuli by reinterpreting their meaning. During down-regulation of negative emotions, wide areas of the prefrontal cortex (PFC) inhibit emotion-related brain areas such as the amygdala. Little is known, however, about how this control activity influences the earliest stages of affective responses by modulating perceptual and attentional areas. The aim of this study is to identify the connectivity patterns between the PFC and the core regions of two well-known attentional networks: the dorsal attentional network (which controls attention volitionally) and the ventral attentional network (which controls attention spontaneously) during reappraisal. We used a novel method to study emotional control processes: the directed transfer function, an autoregressive effective connectivity method based on Granger causality. It was applied to EEG recordings to quantify the direction and intensity of information flow during passively watching (control condition) or reappraising (experimental condition) negative film clips. Reappraisal was mostly associated with increased top-down influences from the right dorsolateral PFC over attentional and perceptual areas, reaching areas including dorsal attentional regions. The left dorsolateral PFC was associated with the activation of the ventral attentional network. Passively watching clips (control condition) resulted in increased flow from attentional areas to the left dorsolateral PFC, what is interpreted as a monitoring process. Thus, reappraisal seems to be related to both volitional and automatic control of attention, triggered by the right and left dorsolateral PFC respectively. PMID:26440605

  4. Mothers' attachment styles and their children's self-reported security, as related to maternal socialization of children's positive affect regulation.

    PubMed

    Gentzler, Amy L; Ramsey, Meagan A; Black, Katelyn R

    2015-01-01

    This study investigated how mothers' attachment was related to their responses to their own and their children's positive events and positive affect (PA). Ninety-seven mothers reported on their attachment and their responses to their own and their 7-12-year-old children's positive events and emotions. Children reported on their mothers' responses to the children's positive events and their attachment security with their mothers. The results indicated that more avoidant mothers reported less intense PA in response to their own and their children's positive events. More avoidant mothers also were less likely to encourage their children to savor positive events (through expressing PA, reflecting on PA or themselves, giving rewards, and affectionate responses). Mothers higher on anxiety reported greater likelihood of dampening (e.g., minimizing the event's importance) their own positive events and reported being more likely to feel discomfort and to reprimand their children for expressing PA. Children's security was predicted by mothers' lower likelihood of encouraging children's dampening and of reprimanding children for PA displays. This study advances the literature on how mothers' attachment is related to the ways in which they regulate their own and their children's PA, which may have implications for children's attachment and developing PA regulation. PMID:26095911

  5. A new locus (leuK) affecting the regulation of branched-chain amino acid, histidine, and tryptophan biosynthetic enzymes.

    PubMed Central

    Brown, C S; West, R; Hilderman, R H; Bayliss, F T; Klines, E L

    1978-01-01

    A locus (leuK) affecting regulation of the leucine operon was selected by isolating a spontaneous Ara+ derivative of an Escherichia coli B/r strain carrying an ara-leu fusion in which the arabinose operon is under leucine control. Genetic analyses by P1 transduction demonstrated that the lesion is located to the right of the galactose operon. Regulation of the biosynthetic enzymes for leucine, isoleucine-valine, histidine, and tryptophan was altered in a strain carrying leuK16. High-level gene expression in the heterozygous merodiploid strain F' leuK+/leuK16) demonstrated the dominance of the mutant allele to the wild-type allele. No apparent effect was observed in the mutant on N-acetylornithinase, a biosynthetic enzyme in the arginine pathway, nor on any of the 18 aminoacyl-tRNA synthetases examined. However, compared with that of the parent strain, the extent of the charging of leucyl-, isoleucyl-, valyl-, histidyl-, and arginyl-tRNA was decreased in the mutant. PMID:355232

  6. SERBP1 affects homologous recombination-mediated DNA repair by regulation of CtIP translation during S phase

    PubMed Central

    Ahn, Jang-Won; Kim, Sunjik; Na, Wooju; Baek, Su-Jin; Kim, Jeong-Hwan; Min, Keehong; Yeom, Jeonghun; Kwak, Hoyun; Jeong, Sunjoo; Lee, Cheolju; Kim, Seon-Young; Choi, Cheol Yong

    2015-01-01

    DNA double-strand breaks (DSBs) are the most severe type of DNA damage and are primarily repaired by non-homologous end joining (NHEJ) and homologous recombination (HR) in the G1 and S/G2 phase, respectively. Although CtBP-interacting protein (CtIP) is crucial in DNA end resection during HR following DSBs, little is known about how CtIP levels increase in an S phase-specific manner. Here, we show that Serpine mRNA binding protein 1 (SERBP1) regulates CtIP expression at the translational level in S phase. In response to camptothecin-mediated DNA DSBs, CHK1 and RPA2 phosphorylation, which are hallmarks of HR activation, was abrogated in SERBP1-depleted cells. We identified CtIP mRNA as a binding target of SERBP1 using RNA immunoprecipitation-coupled RNA sequencing, and confirmed SERBP1 binding to CtIP mRNA in S phase. SERBP1 depletion resulted in reduction of polysome-associated CtIP mRNA and concomitant loss of CtIP expression in S phase. These effects were reversed by reconstituting cells with wild-type SERBP1, but not by SERBP1 ΔRGG, an RNA binding defective mutant, suggesting regulation of CtIP translation by SERBP1 association with CtIP mRNA. These results indicate that SERBP1 affects HR-mediated DNA repair in response to DNA DSBs by regulation of CtIP translation in S phase. PMID:26068472

  7. Complotype affects the extent of down-regulation by Factor I of the C3b feedback cycle in vitro.

    PubMed

    Lay, E; Nutland, S; Smith, J E; Hiles, I; Smith, R A G; Seilly, D J; Buchberger, A; Schwaeble, W; Lachmann, P J

    2015-08-01

    Sera from a large panel of normal subjects were typed for three common polymorphisms, one in C3 (R102G) and two in Factor H (V62I and Y402H), that influence predisposition to age-related macular degeneration and to some forms of kidney disease. Three groups of sera were tested; those that were homozygous for the three risk alleles; those that were heterozygous for all three; and those homozygous for the low-risk alleles. These groups vary in their response to the addition of exogenous Factor I when the alternative complement pathway is activated by zymosan. Both the reduction in the maximum amount of iC3b formed and the rate at which the iC3b is converted to C3dg are affected. For both reactions the at-risk complotype requires higher doses of Factor I to produce similar down-regulation. Because iC3b reacting with the complement receptor CR3 is a major mechanism by which complement activation gives rise to inflammation, the breakdown of iC3b to C3dg can be seen to have major significance for reducing complement-induced inflammation. These findings demonstrate for the first time that sera from subjects with different complement alleles behave as predicted in an in-vitro assay of the down-regulation of the alternative complement pathway by increasing the concentration of Factor I. These results support the hypothesis that exogenous Factor I may be a valuable therapeutic aid for down-regulating hyperactivity of the C3b feedback cycle, thereby providing a treatment for age-related macular degeneration and other inflammatory diseases of later life. PMID:25124117

  8. AMS-dependent and independent regulation of anther transcriptome and comparison with those affected by other Arabidopsis anther genes

    PubMed Central

    2012-01-01

    Background In flowering plants, the development of male reproductive organs is controlled precisely to achieve successful fertilization and reproduction. Despite the increasing knowledge of genes that contribute to anther development, the regulatory mechanisms controlling this process are still unclear. Results In this study, we analyzed the transcriptome profiles of early anthers of sterile mutants aborted microspores (ams) and found that 1,368 genes were differentially expressed in ams compared to wild type anthers, affecting metabolism, transportation, ubiquitination and stress response. Moreover, the lack of significant enrichment of potential AMS binding sites (E-box) in the promoters of differentially expressed genes suggests both direct and indirect regulation for AMS-dependent regulation of anther transcriptome involving other transcription factors. Combining ams transcriptome profiles with those of two other sterile mutants, spl/nzz and ems1/exs, expression of 3,058 genes were altered in at least one mutant. Our investigation of expression patterns of major transcription factor families, such as bHLH, MYB and MADS, suggested that some closely related homologs of known anther developmental genes might also have similar functions. Additionally, comparison of expression levels of genes in different organs suggested that anther-preferential genes could play important roles in anther development. Conclusion Analysis of ams anther transcriptome and its comparison with those of spl/nzz and ems1/exs anthers uncovered overlapping and distinct sets of regulated genes, including those encoding transcription factors and other proteins. These results support an expanded regulatory network for early anther development, providing a series of hypotheses for future experimentation. PMID:22336428

  9. Plant phenolic acids affect the virulence of Pectobacterium aroidearum and P. carotovorum ssp. brasiliense via quorum sensing regulation.

    PubMed

    Joshi, Janak Raj; Burdman, Saul; Lipsky, Alexander; Yariv, Shaked; Yedidia, Iris

    2016-05-01

    Several studies have reported effects of the plant phenolic acids cinnamic acid (CA) and salicylic acid (SA) on the virulence of soft rot enterobacteria. However, the mechanisms involved in these processes are not yet fully understood. Here, we investigated whether CA and SA interfere with the quorum sensing (QS) system of two Pectobacterium species, P. aroidearum and P. carotovorum ssp. brasiliense, which are known to produce N-acyl-homoserine lactone (AHL) QS signals. Our results clearly indicate that both phenolic compounds affect the QS machinery of the two species, consequently altering the expression of bacterial virulence factors. Although, in control treatments, the expression of QS-related genes increased over time, the exposure of bacteria to non-lethal concentrations of CA or SA inhibited the expression of QS genes, including expI, expR, PC1_1442 (luxR transcriptional regulator) and luxS (a component of the AI-2 system). Other virulence genes known to be regulated by the QS system, such as pecS, pel, peh and yheO, were also down-regulated relative to the control. In agreement with the low levels of expression of expI and expR, CA and SA also reduced the level of the AHL signal. The effects of CA and SA on AHL signalling were confirmed in compensation assays, in which exogenous application of N-(β-ketocaproyl)-l-homoserine lactone (eAHL) led to the recovery of the reduction in virulence caused by the two phenolic acids. Collectively, the results of gene expression studies, bioluminescence assays, virulence assays and compensation assays with eAHL clearly support a mechanism by which CA and SA interfere with Pectobacterium virulence via the QS machinery. PMID:26177258

  10. The luxS Gene of Streptococcus pyogenes Regulates Expression of Genes That Affect Internalization by Epithelial Cells

    PubMed Central

    Marouni, Mehran J.; Sela, Shlomo

    2003-01-01

    The gram-positive pathogen Streptococcus pyogenes was recently reported to possess a homologue of the luxS gene that is responsible for the production of autoinducer 2, which participates in quorum sensing of both gram-positive and gram-negative bacteria. To test the effect of LuxS on streptococcal internalization, a LuxS mutant was constructed in strain SP268, an invasive M3 serotype. Functional analysis of the mutant revealed that it was internalized by HEp-2 cells with higher efficiency than the wild type (wt). Several genes, including hasA (hyaluronic acid synthesis), speB (streptococcal pyrogenic exotoxin B), and csrR (capsule synthesis regulator), a part of a two-component regulatory system, are known to affect the internalization of strain SP268 (J. Jadoun, O. Eyal, and S. Sela, Infect. Immun. 70:462-469, 2002). Therefore, the expression of these genes in the mutant and in the wt was examined. LuxS mutation significantly reduced the mRNA level of speB and increased the mRNA level of emm3. No substantial effect was observed on transcription of hasA and csrR. Yet less hyaluronic acid capsule was expressed in the mutant. Further analysis revealed that luxS is under the regulation of the two-component global regulator CsrR. Our results indicate that LuxS activity in strain SP268 plays an important role in the expression of virulence factors associated with epithelial cell internalization. PMID:14500483

  11. The luxS gene of Streptococcus pyogenes regulates expression of genes that affect internalization by epithelial cells.

    PubMed

    Marouni, Mehran J; Sela, Shlomo

    2003-10-01

    The gram-positive pathogen Streptococcus pyogenes was recently reported to possess a homologue of the luxS gene that is responsible for the production of autoinducer 2, which participates in quorum sensing of both gram-positive and gram-negative bacteria. To test the effect of LuxS on streptococcal internalization, a LuxS mutant was constructed in strain SP268, an invasive M3 serotype. Functional analysis of the mutant revealed that it was internalized by HEp-2 cells with higher efficiency than the wild type (wt). Several genes, including hasA (hyaluronic acid synthesis), speB (streptococcal pyrogenic exotoxin B), and csrR (capsule synthesis regulator), a part of a two-component regulatory system, are known to affect the internalization of strain SP268 (J. Jadoun, O. Eyal, and S. Sela, Infect. Immun. 70:462-469, 2002). Therefore, the expression of these genes in the mutant and in the wt was examined. LuxS mutation significantly reduced the mRNA level of speB and increased the mRNA level of emm3. No substantial effect was observed on transcription of hasA and csrR. Yet less hyaluronic acid capsule was expressed in the mutant. Further analysis revealed that luxS is under the regulation of the two-component global regulator CsrR. Our results indicate that LuxS activity in strain SP268 plays an important role in the expression of virulence factors associated with epithelial cell internalization. PMID:14500483

  12. Mathematical modeling of the cells repair regulations in Nasopharyngeal carcinoma.

    PubMed

    Adi-Kusumo, Fajar; Wiraya, Ario

    2016-07-01

    Nasopharyngeal Carcinoma (NPC) is a malignant cancer which is caused by the activation of Epstein-Barr Virus (EBV) via some external factors. In the cells repair regulations, the p53 gene mutation can be used as the early indication of the NPC growth. The NPC growth is due to the DNA damage accumulation caused by the EBV infection. In this paper we construct the cells repair regulations model to characterize the NPC growth. The model is a 15 dimensional of first order ODE system and consists the proteins and enzymes reactions. We do some numerical simulations to show the inactivation of the phosphorylated and acetylated p53, and the chromosomal instability of p53 gene, which can be used as the earlier stage detection of NPC. PMID:27140528

  13. Computational Modeling of Morphogenesis Regulated by Mechanical Feedback

    PubMed Central

    Ramasubramanian, Ashok; Taber, Larry A.

    2008-01-01

    Mechanical forces cause changes in form during embryogenesis and likely play a role in regulating these changes. This paper explores the idea that changes in homeostatic tissue stress (target stress), possibly modulated by genes, drive some morphogenetic processes. Computational models are presented to illustrate how regional variations in target stress can cause a range of complex behaviors involving the bending of epithelia. These models include growth and cytoskeletal contraction regulated by stress-based mechanical feedback. All simulations were carried out using the commercial finite element code ABAQUS, with growth and contraction included by modifying the zero-stress state in the material constitutive relations. Results presented for bending of bilayered beams and invagination of cylindrical and spherical shells provide insight into some of the mechanical aspects that must be considered in studying morphogenetic mechanisms. PMID:17318485

  14. The regulation of cognitive enhancement devices: extending the medical model

    PubMed Central

    Maslen, Hannah; Douglas, Thomas; Cohen Kadosh, Roi; Levy, Neil; Savulescu, Julian

    2014-01-01

    This article presents a model for regulating cognitive enhancement devices (CEDs). Recently, it has become very easy for individuals to purchase devices which directly modulate brain function. For example, transcranial direct current stimulators are increasingly being produced and marketed online as devices for cognitive enhancement. Despite posing risks in a similar way to medical devices, devices that do not make any therapeutic claims do not have to meet anything more than basic product safety standards. We present the case for extending existing medical device legislation to cover CEDs. Medical devices and CEDs operate by the same or similar mechanisms and pose the same or similar risks. This fact coupled with the arbitrariness of the line between treatment and enhancement count in favour of regulating these devices in the same way. In arguing for this regulatory model, the paper highlights potential challenges to its implementation, and suggests solutions. PMID:25243073

  15. Modeling cutinase enzyme regulation in polyethylene terepthalate plastic biodegradation

    NASA Astrophysics Data System (ADS)

    Apri, M.; Silmi, M.; Heryanto, T. E.; Moeis, M. R.

    2016-04-01

    PET (Polyethylene terephthalate) is a plastic material that is commonly used in our daily life. The high production of PET and others plastics that can be up to three hundred million tons per year, is not matched by its degradation rate and hence leads to environmental pollution. To overcome this problem, we develop a biodegradation system. This system utilizes LC Cutinase enzyme produced by engineered escherichia coli bacteria to degrade PET. To make the system works efficaciously, it is important to understand the mechanism underlying its enzyme regulation. Therefore, we construct a mathematical model to describe the regulation of LC Cutinase production. The stability of the model is analyzed. We show that the designated biodegradation system can give an oscillatory behavior that is very important to control the amount of inclusion body (the miss-folded proteins that reduce the efficiency of the biodegradation system).

  16. Stochastic models of gene expression and post-transcriptional regulation

    NASA Astrophysics Data System (ADS)

    Pendar, Hodjat; Kulkarni, Rahul; Jia, Tao

    2011-10-01

    The intrinsic stochasticity of gene expression can give rise to phenotypic heterogeneity in a population of genetically identical cells. Correspondingly, there is considerable interest in understanding how different molecular mechanisms impact the 'noise' in gene expression. Of particular interest are post-transcriptional regulatory mechanisms involving genes called small RNAs, which control important processes such as development and cancer. We propose and analyze general stochastic models of gene expression and derive exact analytical expressions quantifying the noise in protein distributions [1]. Focusing on specific regulatory mechanisms, we analyze a general model for post-transcriptional regulation of stochastic gene expression [2]. The results obtained provide new insights into the role of post-transcriptional regulation in controlling the noise in gene expression. [4pt] [1] T. Jia and R. V. Kulkarni, Phys. Rev. Lett.,106, 058102 (2011) [0pt] [2] T. Jia and R. V. Kulkarni, Phys. Rev. Lett., 105, 018101 (2010)

  17. Model rocket engine burn injuries: the need for stricter regulation.

    PubMed

    Lynch, M T; Bellian, K T; Edlich, R F; Himel, H N

    1994-01-01

    During the 18-year period from 1975 to 1992, the Consumer Product Safety Commission's National Electronic Injury Surveillance System database received reports of 18 burn injuries caused by model rocketry sets and their engines. Children in the age range of 11 to 15 years, who frequently use the products inappropriately, are the pediatric population most at risk. Unfortunately, current regulations do not impose age restrictions on the purchase or use of these products; consequently, the industry sets its own age limits. The current regulations appear to be inadequate and need to be altered to cover the population at risk. Specific recommendations include imposing an adequate age limit and improving the labelling of these products. Two case reports are presented that exemplify the typical burn injuries sustained from model rocket engine accidents. PMID:8040589

  18. Grain setting defect1, Encoding a Remorin Protein, Affects the Grain Setting in Rice through Regulating Plasmodesmatal Conductance1[W

    PubMed Central

    Gui, Jinshan; Liu, Chang; Shen, Junhui; Li, Laigeng

    2014-01-01

    Effective grain filling is one of the key determinants of grain setting in rice (Oryza sativa). Grain setting defect1 (GSD1), which encodes a putative remorin protein, was found to affect grain setting in rice. Investigation of the phenotype of a transfer DNA insertion mutant (gsd1-Dominant) with enhanced GSD1 expression revealed abnormalities including a reduced grain setting rate, accumulation of carbohydrates in leaves, and lower soluble sugar content in the phloem exudates. GSD1 was found to be specifically expressed in the plasma membrane and plasmodesmata (PD) of phloem companion cells. Experimental evidence suggests that the phenotype of the gsd1-Dominant mutant is caused by defects in the grain-filling process as a result of the impaired transport of carbohydrates from the photosynthetic site to the phloem. GSD1 functioned in affecting PD conductance by interacting with rice ACTIN1 in association with the PD callose binding protein1. Together, our results suggest that GSD1 may play a role in regulating photoassimilate translocation through the symplastic pathway to impact grain setting in rice. PMID:25253885

  19. Once More with Feeling: Affect and Playing with the TGfU Model

    ERIC Educational Resources Information Center

    Pope, Clive C.

    2005-01-01

    Certainly, the process of decision-making and problem-solving in a shifting playing environment lies at the core of the Teaching Games for Understanding (TGfU) model. What is not clear is how, at the time of decision-making, players' feelings or affective factors and their subsequent influence on thinking, influence these processes. Affect has a…

  20. Predicting wetland plant community responses to proposed water-level-regulation plans for Lake Ontario: GIS-based modeling

    USGS Publications Warehouse

    Wilcox, D.A.; Xie, Y.

    2007-01-01

    Integrated, GIS-based, wetland predictive models were constructed to assist in predicting the responses of wetland plant communities to proposed new water-level regulation plans for Lake Ontario. The modeling exercise consisted of four major components: 1) building individual site wetland geometric models; 2) constructing generalized wetland geometric models representing specific types of wetlands (rectangle model for drowned river mouth wetlands, half ring model for open embayment wetlands, half ellipse model for protected embayment wetlands, and ellipse model for barrier beach wetlands); 3) assigning wetland plant profiles to the generalized wetland geometric models that identify associations between past flooding / dewatering events and the regulated water-level changes of a proposed water-level-regulation plan; and 4) predicting relevant proportions of wetland plant communities and the time durations during which they would be affected under proposed regulation plans. Based on this conceptual foundation, the predictive models were constructed using bathymetric and topographic wetland models and technical procedures operating on the platform of ArcGIS. An example of the model processes and outputs for the drowned river mouth wetland model using a test regulation plan illustrates the four components and, when compared against other test regulation plans, provided results that met ecological expectations. The model results were also compared to independent data collected by photointerpretation. Although data collections were not directly comparable, the predicted extent of meadow marsh in years in which photographs were taken was significantly correlated with extent of mapped meadow marsh in all but barrier beach wetlands. The predictive model for wetland plant communities provided valuable input into International Joint Commission deliberations on new regulation plans and was also incorporated into faunal predictive models used for that purpose.

  1. Mentoring Resulting in a New Model: Affect-Centered Transformational Leadership

    ERIC Educational Resources Information Center

    Moffett, David W.; Tejeda, Armando R.

    2014-01-01

    The authors were professor and student, in a doctoral leadership course, during fall semester of 2013-2014. Across the term the professor mentored the mentee, guiding him to the creation of the next, needed model for leadership. The new model, known as The Affect-Centered Transformational Leadership Model, came about as the result. Becoming an…

  2. Dynamic model of gene regulation for the lac operon

    NASA Astrophysics Data System (ADS)

    Angelova, Maia; Ben-Halim, Asma

    2011-03-01

    Gene regulatory network is a collection of DNA which interact with each other and with other matter in the cell. The lac operon is an example of a relatively simple genetic network and is one of the best-studied structures in the Escherichia coli bacteria. In this work we consider a deterministic model of the lac operon with a noise term, representing the stochastic nature of the regulation. The model is written in terms of a system of simultaneous first order differential equations with delays. We investigate an analytical and numerical solution and analyse the range of values for the parameters corresponding to a stable solution.

  3. The Transcript and Metabolite Networks Affected by the Two Clades of Arabidopsis Glucosinolate Biosynthesis Regulators1[W

    PubMed Central

    Malitsky, Sergey; Blum, Eyal; Less, Hadar; Venger, Ilya; Elbaz, Moshe; Morin, Shai; Eshed, Yuval; Aharoni, Asaph

    2008-01-01

    In this study, transcriptomics and metabolomics data were integrated in order to examine the regulation of glucosinolate (GS) biosynthesis in Arabidopsis (Arabidopsis thaliana) and its interface with pathways of primary metabolism. Our genetic material for analyses were transgenic plants overexpressing members of two clades of genes (ALTERED TRYPTOPHAN REGULATION1 [ATR1]-like and MYB28-like) that regulate the aliphatic and indole GS biosynthetic pathways (AGs and IGs, respectively). We show that activity of these regulators is not restricted to the metabolic space surrounding GS biosynthesis but is tightly linked to more distal metabolic networks of primary metabolism. This suggests that with similarity to the regulators we have investigated here, other factors controlling pathways of secondary metabolism might also control core pathways of central metabolism. The relatively broad view of transcripts and metabolites altered in transgenic plants overexpressing the different factors underlined novel links of GS metabolism to additional metabolic pathways, including those of jasmonic acid, folate, benzoic acid, and various phenylpropanoids. It also revealed transcriptional and metabolic hubs in the “distal” network of metabolic pathways supplying precursors to GS biosynthesis and that overexpression of the ATR1-like clade genes has a much broader effect on the metabolism of indolic compounds than described previously. While the reciprocal, negative cross talk between the methionine and tryptophan pathways that generate GSs in Arabidopsis has been suggested previously, we now show that it is not restricted to AGs and IGs but includes additional metabolites, such as the phytoalexin camalexin. Combining the profiling data of transgenic lines with gene expression correlation analysis allowed us to propose a model of how the balance in the metabolic network is maintained by the GS biosynthesis regulators. It appears that ATR1/MYB34 is an important mediator between the

  4. Psychodynamic Emotional Regulation in View of Wolpe's Desensitization Model.

    PubMed

    Rabinovich, Merav

    2016-01-01

    The current research belongs to the stream of theoretical integration and establishes a theoretical platform for integrative psychotherapy in anxiety disorders. Qualitative metasynthesis procedures were applied to 40 peer-reviewed psychoanalytic articles involving emotional regulation. The concept of psychodynamic emotional regulation was found to be connected with the categories of desensitization, gradual exposure, containment, and transference. This article presents a model according to which psychoanalytic psychotherapy allows anxiety to be tolerated while following the core principles of systematic desensitization. It is shown that despite the antiresearch image of psychoanalytic psychotherapy, its foundations obey evidence-based principles. The findings imply that anxiety tolerance might be a key goal in which the cumulative wisdom of the different therapies can be used to optimize psychotherapy outcomes. PMID:27029107

  5. Using item response theory to investigate the structure of anticipated affect: do self-reports about future affective reactions conform to typical or maximal models?

    PubMed Central

    Zampetakis, Leonidas A.; Lerakis, Manolis; Kafetsios, Konstantinos; Moustakis, Vassilis

    2015-01-01

    In the present research, we used item response theory (IRT) to examine whether effective predictions (anticipated affect) conforms to a typical (i.e., what people usually do) or a maximal behavior process (i.e., what people can do). The former, correspond to non-monotonic ideal point IRT models, whereas the latter correspond to monotonic dominance IRT models. A convenience, cross-sectional student sample (N = 1624) was used. Participants were asked to report on anticipated positive and negative affect around a hypothetical event (emotions surrounding the start of a new business). We carried out analysis comparing graded response model (GRM), a dominance IRT model, against generalized graded unfolding model, an unfolding IRT model. We found that the GRM provided a better fit to the data. Findings suggest that the self-report responses to anticipated affect conform to dominance response process (i.e., maximal behavior). The paper also discusses implications for a growing literature on anticipated affect. PMID:26441806

  6. Modeling endocrine regulation of the menstrual cycle using delay differential equations.

    PubMed

    Harris, Leona A; Selgrade, James F

    2014-11-01

    This article reviews an effective mathematical procedure for modeling hormonal regulation of the menstrual cycle of adult women. The procedure captures the effects of hormones secreted by several glands over multiple time scales. The specific model described here consists of 13 nonlinear, delay, differential equations with 44 parameters and correctly predicts blood levels of ovarian and pituitary hormones found in the biological literature for normally cycling women. In addition to this normal cycle, the model exhibits another stable cycle which may describe a biologically feasible "abnormal" condition such as polycystic ovarian syndrome. Model simulations illustrate how one cycle can be perturbed to the other cycle. Perturbations due to the exogenous administration of each ovarian hormone are examined. This model may be used to test the effects of hormone therapies on abnormally cycling women as well as the effects of exogenous compounds on normally cycling women. Sensitive parameters are identified and bifurcations in model behavior with respect to parameter changes are discussed. Modeling various aspects of menstrual cycle regulation should be helpful in predicting successful hormone therapies, in studying the phenomenon of cycle synchronization and in understanding many factors affecting the aging of the female reproductive endocrine system. PMID:25180928

  7. Psychological Mechanisms Mediating Effects Between Trauma and Psychotic Symptoms: The Role of Affect Regulation, Intrusive Trauma Memory, Beliefs, and Depression.

    PubMed

    Hardy, Amy; Emsley, Richard; Freeman, Daniel; Bebbington, Paul; Garety, Philippa A; Kuipers, Elizabeth E; Dunn, Graham; Fowler, David

    2016-07-01

    Evidence suggests a causal role for trauma in psychosis, particularly for childhood victimization. However, the establishment of underlying trauma-related mechanisms would strengthen the causal argument. In a sample of people with relapsing psychosis (n = 228), we tested hypothesized mechanisms specifically related to impaired affect regulation, intrusive trauma memory, beliefs, and depression. The majority of participants (74.1%) reported victimization trauma, and a fifth (21.5%) met symptomatic criteria for Posttraumatic Stress Disorder. We found a specific link between childhood sexual abuse and auditory hallucinations (adjusted OR = 2.21, SE = 0.74, P = .018). This relationship was mediated by posttraumatic avoidance and numbing (OR = 1.48, SE = 0.19, P = .038) and hyperarousal (OR = 1.44, SE = 0.18, P = .045), but not intrusive trauma memory, negative beliefs or depression. In contrast, childhood emotional abuse was specifically associated with delusions, both persecutory (adjusted OR = 2.21, SE = 0.68, P = .009) and referential (adjusted OR = 2.43, SE = 0.74, P = .004). The link with persecutory delusions was mediated by negative-other beliefs (OR = 1.36, SE = 0.14, P = .024), but not posttraumatic stress symptoms, negative-self beliefs, or depression. There was no evidence of mediation for referential delusions. No relationships were identified between childhood physical abuse and psychosis. The findings underline the role of cognitive-affective processes in the relationship between trauma and symptoms, and the importance of assessing and treating victimization and its psychological consequences in people with psychosis. PMID:27460616

  8. Psychological Mechanisms Mediating Effects Between Trauma and Psychotic Symptoms: The Role of Affect Regulation, Intrusive Trauma Memory, Beliefs, and Depression

    PubMed Central

    Hardy, Amy; Emsley, Richard; Freeman, Daniel; Bebbington, Paul; Garety, Philippa A.; Kuipers, Elizabeth E.; Dunn, Graham; Fowler, David

    2016-01-01

    Evidence suggests a causal role for trauma in psychosis, particularly for childhood victimization. However, the establishment of underlying trauma-related mechanisms would strengthen the causal argument. In a sample of people with relapsing psychosis (n = 228), we tested hypothesized mechanisms specifically related to impaired affect regulation, intrusive trauma memory, beliefs, and depression. The majority of participants (74.1%) reported victimization trauma, and a fifth (21.5%) met symptomatic criteria for Posttraumatic Stress Disorder. We found a specific link between childhood sexual abuse and auditory hallucinations (adjusted OR = 2.21, SE = 0.74, P = .018). This relationship was mediated by posttraumatic avoidance and numbing (OR = 1.48, SE = 0.19, P = .038) and hyperarousal (OR = 1.44, SE = 0.18, P = .045), but not intrusive trauma memory, negative beliefs or depression. In contrast, childhood emotional abuse was specifically associated with delusions, both persecutory (adjusted OR = 2.21, SE = 0.68, P = .009) and referential (adjusted OR = 2.43, SE = 0.74, P = .004). The link with persecutory delusions was mediated by negative-other beliefs (OR = 1.36, SE = 0.14, P = .024), but not posttraumatic stress symptoms, negative-self beliefs, or depression. There was no evidence of mediation for referential delusions. No relationships were identified between childhood physical abuse and psychosis. The findings underline the role of cognitive-affective processes in the relationship between trauma and symptoms, and the importance of assessing and treating victimization and its psychological consequences in people with psychosis. PMID:27460616

  9. Tamm-Horsfall Protein Regulates Circulating and Renal Cytokines by Affecting Glomerular Filtration Rate and Acting as a Urinary Cytokine Trap*

    PubMed Central

    Liu, Yan; El-Achkar, Tarek M.; Wu, Xue-Ru

    2012-01-01

    Although few organ systems play a more important role than the kidneys in cytokine catabolism, the mechanism(s) regulating this pivotal physiological function and how its deficiency affects systemic cytokine homeostasis remain unclear. Here we show that elimination of Tamm-Horsfall protein (THP) expression from mouse kidneys caused a marked elevation of circulating IFN-γ, IL1α, TNF-α, IL6, CXCL1, and IL13. Accompanying this were enlarged spleens with prominent white-pulp macrophage infiltration. Lipopolysaccharide (LPS) exacerbated the increase of serum cytokines without a corresponding increase in their urinary excretion in THP knock-out (KO) mice. This, along with the rise of serum cystatin C and the reduced inulin and creatinine clearance from the circulation, suggested that diminished glomerular filtration may contribute to reduced cytokine clearance in THP KO mice both at the baseline and under stress. Unlike wild-type mice where renal and urinary cytokines formed specific in vivo complexes with THP, this “trapping” effect was absent in THP KO mice, thus explaining why cytokine signaling pathways were activated in renal epithelial cells in such mice. Our study provides new evidence implicating an important role of THP in influencing cytokine clearance and acting as a decoy receptor for urinary cytokines. Based on these and other data, we present a unifying model that underscores the role of THP as a major regulator of renal and systemic immunity. PMID:22451664

  10. Fear is only as deep as the mind allows: a coordinate-based meta-analysis of neuroimaging studies on the regulation of negative affect.

    PubMed

    Diekhof, Esther Kristina; Geier, Katharina; Falkai, Peter; Gruber, Oliver

    2011-09-01

    Humans have the ability to control negative affect and perceived fear. Nevertheless, it is still unclear whether this affect regulation capacity relies on a common neural mechanism in different experimental domains. Here, we sought to identify commonalities in regulatory brain activation in the domains of fear extinction, placebo, and cognitive emotion regulation. Using coordinate-based activation-likelihood estimation meta-analysis we intended to elucidate concordant hyperactivations and the associated deactivations in the three experimental domains, when human subjects successfully diminished negative affect. Our data show that only one region in the ventromedial prefrontal cortex (VMPFC) controlled negative affective responses and reduced the degree of subjectively perceived unpleasantness independent of the experimental domain. This down-regulation of negative affect was further accompanied by a concordant reduction of activation in the left amygdala. Finally, the soothing effect of placebo treatments and cognitive reappraisal strategies, but not extinction retrieval, was specifically accompanied by a coherent hyperactivation in the anterior cingulate and the insular cortex. Collectively, our data strongly imply that the human VMPFC may represent a domain-general controller of perceived fear and aversiveness that modulates negative affective responses in phylogenetically older structures of the emotion processing system. In addition, higher-level regulation strategies may further engage complementary neural resources to effectively deal with the emotion-eliciting events. PMID:21669291

  11. GlmS and NagB Regulate Amino Sugar Metabolism in Opposing Directions and Affect Streptococcus mutans Virulence

    PubMed Central

    Kawada-Matsuo, Miki; Mazda, Yusuke; Oogai, Yuichi; Kajiya, Mikihito; Kawai, Toshihisa; Yamada, Sakuo; Miyawaki, Shouichi; Oho, Takahiko; Komatsuzawa, Hitoshi

    2012-01-01

    Streptococcus mutans is a cariogenic pathogen that produces an extracellular polysaccharide (glucan) from dietary sugars, which allows it to establish a reproductive niche and secrete acids that degrade tooth enamel. While two enzymes (GlmS and NagB) are known to be key factors affecting the entrance of amino sugars into glycolysis and cell wall synthesis in several other bacteria, their roles in S. mutans remain unclear. Therefore, we investigated the roles of GlmS and NagB in S. mutans sugar metabolism and determined whether they have an effect on virulence. NagB expression increased in the presence of GlcNAc while GlmS expression decreased, suggesting that the regulation of these enzymes, which functionally oppose one another, is dependent on the concentration of environmental GlcNAc. A glmS-inactivated mutant could not grow in the absence of GlcNAc, while nagB-inactivated mutant growth was decreased in the presence of GlcNAc. Also, nagB inactivation was found to decrease the expression of virulence factors, including cell-surface protein antigen and glucosyltransferase, and to decrease biofilm formation and saliva-induced S. mutans aggregation, while glmS inactivation had the opposite effects on virulence factor expression and bacterial aggregation. Our results suggest that GlmS and NagB function in sugar metabolism in opposing directions, increasing and decreasing S. mutans virulence, respectively. PMID:22438919

  12. FBXW7 and USP7 regulate CCDC6 turnover during the cell cycle and affect cancer drugs susceptibility in NSCLC

    PubMed Central

    Merolla, Francesco; Poser, Ina; Visconti, Roberta; Ilardi, Gennaro; Paladino, Simona; Inuzuka, Hiroyuki; Guggino, Gianluca; Monaco, Roberto; Colecchia, David; Monaco, Guglielmo; Cerrato, Aniello; Chiariello, Mario; Denning, Krista; Claudio, Pier Paolo; Staibano, Stefania; Celetti, Angela

    2015-01-01

    CCDC6 gene product is a pro-apoptotic protein substrate of ATM, whose loss or inactivation enhances tumour progression. In primary tumours, the impaired function of CCDC6 protein has been ascribed to CCDC6 rearrangements and to somatic mutations in several neoplasia. Recently, low levels of CCDC6 protein, in NSCLC, have been correlated with tumor prognosis. However, the mechanisms responsible for the variable levels of CCDC6 in primary tumors have not been described yet. We show that CCDC6 turnover is regulated in a cell cycle dependent manner. CCDC6 undergoes a cyclic variation in the phosphorylated status and in protein levels that peak at G2 and decrease in mitosis. The reduced stability of CCDC6 in the M phase is dependent on mitotic kinases and on degron motifs that are present in CCDC6 and direct the recruitment of CCDC6 to the FBXW7 E3 Ubl. The de-ubiquitinase enzyme USP7 appears responsible of the fine tuning of the CCDC6 stability, affecting cells behaviour and drug response. Thus, we propose that the amount of CCDC6 protein in primary tumors, as reported in lung, may depend on the impairment of the CCDC6 turnover due to altered protein-protein interaction and post-translational modifications and may be critical in optimizing personalized therapy. PMID:25885523

  13. Arousal regulation and affective adaptation to human responsiveness by a robot that explores and learns a novel environment.

    PubMed

    Hiolle, Antoine; Lewis, Matthew; Cañamero, Lola

    2014-01-01

    In the context of our work in developmental robotics regarding robot-human caregiver interactions, in this paper we investigate how a "baby" robot that explores and learns novel environments can adapt its affective regulatory behavior of soliciting help from a "caregiver" to the preferences shown by the caregiver in terms of varying responsiveness. We build on two strands of previous work that assessed independently (a) the differences between two "idealized" robot profiles-a "needy" and an "independent" robot-in terms of their use of a caregiver as a means to regulate the "stress" (arousal) produced by the exploration and learning of a novel environment, and (b) the effects on the robot behaviors of two caregiving profiles varying in their responsiveness-"responsive" and "non-responsive"-to the regulatory requests of the robot. Going beyond previous work, in this paper we (a) assess the effects that the varying regulatory behavior of the two robot profiles has on the exploratory and learning patterns of the robots; (b) bring together the two strands previously investigated in isolation and take a step further by endowing the robot with the capability to adapt its regulatory behavior along the "needy" and "independent" axis as a function of the varying responsiveness of the caregiver; and (c) analyze the effects that the varying regulatory behavior has on the exploratory and learning patterns of the adaptive robot. PMID:24860492

  14. Arousal regulation and affective adaptation to human responsiveness by a robot that explores and learns a novel environment

    PubMed Central

    Hiolle, Antoine; Lewis, Matthew; Cañamero, Lola

    2014-01-01

    In the context of our work in developmental robotics regarding robot–human caregiver interactions, in this paper we investigate how a “baby” robot that explores and learns novel environments can adapt its affective regulatory behavior of soliciting help from a “caregiver” to the preferences shown by the caregiver in terms of varying responsiveness. We build on two strands of previous work that assessed independently (a) the differences between two “idealized” robot profiles—a “needy” and an “independent” robot—in terms of their use of a caregiver as a means to regulate the “stress” (arousal) produced by the exploration and learning of a novel environment, and (b) the effects on the robot behaviors of two caregiving profiles varying in their responsiveness—“responsive” and “non-responsive”—to the regulatory requests of the robot. Going beyond previous work, in this paper we (a) assess the effects that the varying regulatory behavior of the two robot profiles has on the exploratory and learning patterns of the robots; (b) bring together the two strands previously investigated in isolation and take a step further by endowing the robot with the capability to adapt its regulatory behavior along the “needy” and “independent” axis as a function of the varying responsiveness of the caregiver; and (c) analyze the effects that the varying regulatory behavior has on the exploratory and learning patterns of the adaptive robot. PMID:24860492

  15. Euthanasia: how proponents justify it and provide models for regulation.

    PubMed

    Daruwala, Anhaita

    2002-01-01

    Life prolonging advances in medicine have raised debate about the concept and clinical practice of euthanasia for terminally ill patients. This debate involves the need for protection of patients' rights in their delicate condition, while providing them with the right to end their own life, if they choose to do so. This paper addresses how proponents justify euthanasia in societies that have legalized it, while ensuring that patients asking for a merciful death do not get exploited by the system. Regulation models are thus adapted from the Dutch and Oregon medical systems. PMID:12755102

  16. Modelling impacts of regulation on flows to the Lowbidgee floodplain of the Murrumbidgee River, Australia

    NASA Astrophysics Data System (ADS)

    Ren, Shiquan; Kingsford, Richard T.

    2014-11-01

    Major wetland systems have been significantly affected by alteration of flows by dams and subsequent abstraction upstream around the world. Estimating the level of this impact is particularly difficult where there is high flow variability, such as dryland rivers in Australia. Such information remains critical for assessing ecological impacts to ecosystems (e.g. long-lived flood-dependent trees). To determine effects of flow reduction to a large floodplain wetland, we built statistical flow models, integrated flow and flood modelling (IFFM), for the extensive and ecologically important Lowbidgee wetland, supplied by the Murrumbidgee River, based on local annual rainfall and upstream flow data (1880-2010). Large volumes of water are diverted upstream primarily for irrigation and to Australia's capital city, Canberra, achieved with 26 large dams: Burrinjuck Dam, Snowy Mountains Scheme dams and other upper catchment dams. We identified two periods using structural change analysis, low (before 1957) and high (after 1958) regulated periods; the year marked significant alteration in monthly flow at Redbank gauge, within the Lowbidgee wetland, after which most major dams were built. To determine differences in flow between these periods, we developed two models for three flow gauges on the lower Murrumbidgee River: Hay, Maude and Redbank. The latter two were within the floodplain wetland. The models were based on annual rainfall from stations in the upper catchment and flow, using LOESS and leave-one-out samples without overfitting. This flexible local polynomial regression method was a useful approach to modelling complex processes without theoretical models. The proposed low and high regulated models performed well using the goodness of fit (Nash-Sutcliffe coefficient of efficiency ⩾91.5%) and Kolmogorov-Smirnov test (p > 0.9999), i.e., there was no significant difference between the observed and fitted distributions of flow data at the Hay, Maude and Redbank flow

  17. Modeling Systems-Level Regulation of Host Immune Responses

    PubMed Central

    Thakar, Juilee; Pilione, Mylisa; Kirimanjeswara, Girish; Harvill, Eric T; Albert, Réka

    2007-01-01

    Many pathogens are able to manipulate the signaling pathways responsible for the generation of host immune responses. Here we examine and model a respiratory infection system in which disruption of host immune functions or of bacterial factors changes the dynamics of the infection. We synthesize the network of interactions between host immune components and two closely related bacteria in the genus Bordetellae. We incorporate existing experimental information on the timing of immune regulatory events into a discrete dynamic model, and verify the model by comparing the effects of simulated disruptions to the experimental outcome of knockout mutations. Our model indicates that the infection time course of both Bordetellae can be separated into three distinct phases based on the most active immune processes. We compare and discuss the effect of the species-specific virulence factors on disrupting the immune response during their infection of naive, antibody-treated, diseased, or convalescent hosts. Our model offers predictions regarding cytokine regulation, key immune components, and clearance of secondary infections; we experimentally validate two of these predictions. This type of modeling provides new insights into the virulence, pathogenesis, and host adaptation of disease-causing microorganisms and allows systems-level analysis that is not always possible using traditional methods. PMID:17559300

  18. The two-process model of sleep regulation: a reappraisal.

    PubMed

    Borbély, Alexander A; Daan, Serge; Wirz-Justice, Anna; Deboer, Tom

    2016-04-01

    In the last three decades the two-process model of sleep regulation has served as a major conceptual framework in sleep research. It has been applied widely in studies on fatigue and performance and to dissect individual differences in sleep regulation. The model posits that a homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C), with time-courses derived from physiological and behavioural variables. The model simulates successfully the timing and intensity of sleep in diverse experimental protocols. Electrophysiological recordings from the suprachiasmatic nuclei (SCN) suggest that S and C interact continuously. Oscillators outside the SCN that are linked to energy metabolism are evident in SCN-lesioned arrhythmic animals subjected to restricted feeding or methamphetamine administration, as well as in human subjects during internal desynchronization. In intact animals these peripheral oscillators may dissociate from the central pacemaker rhythm. A sleep/fast and wake/feed phase segregate antagonistic anabolic and catabolic metabolic processes in peripheral tissues. A deficiency of Process S was proposed to account for both depressive sleep disturbances and the antidepressant effect of sleep deprivation. The model supported the development of novel non-pharmacological treatment paradigms in psychiatry, based on manipulating circadian phase, sleep and light exposure. In conclusion, the model remains conceptually useful for promoting the integration of sleep and circadian rhythm research. Sleep appears to have not only a short-term, use-dependent function; it also serves to enforce rest and fasting, thereby supporting the optimization of metabolic processes at the appropriate phase of the 24-h cycle. PMID:26762182

  19. Insulin regulates primordial-follicle assembly in vitro by affecting germ-cell apoptosis and elevating oestrogen.

    PubMed

    Feng, Xin-Lei; Sun, Yuan-Chao; Zhang, Min; Cheng, Shun-Feng; Feng, Yan-Ni; Liu, Jing-Cai; Wang, Hong-Hui; Li, Lan; Qin, Guo-Qing; Shen, Wei

    2015-11-01

    Insulin is a protein secreted by pancreatic β-cells, which plays an important role in the regulation of ovarian function. However, the specific molecular mechanism of its function remains largely unknown. This study aimed to assess the effect of insulin on mouse folliculogenesis using an in vitro ovary-culture model. The results demonstrated that insulin promoted the proliferation of ovarian granulosa cells in vitro, and thereby accelerated the progress of folliculogenesis (the percentage of oocytes in cysts declined from 42.6% to 29.3%); however, the percentage of apoptotic oocytes increased after insulin treatment. Further investigation indicated that apoptosis occurred mainly in germ-cell cysts. After 3 days of insulin treatment, oestrogen in the culture medium of mouse ovaries significantly increased (P<0.01), while the lower dose of oestrogen promoted primordial-follicle assembly in vitro. In conclusion, insulin promoted folliculogenesis by facilitating germ-cell apoptosis within the cysts and upregulating oestrogen levels. PMID:24931389

  20. Thermodynamic State Ensemble Models of cis-Regulation

    PubMed Central

    Sherman, Marc S.; Cohen, Barak A.

    2012-01-01

    A major goal in computational biology is to develop models that accurately predict a gene's expression from its surrounding regulatory DNA. Here we present one class of such models, thermodynamic state ensemble models. We describe the biochemical derivation of the thermodynamic framework in simple terms, and lay out the mathematical components that comprise each model. These components include (1) the possible states of a promoter, where a state is defined as a particular arrangement of transcription factors bound to a DNA promoter, (2) the binding constants that describe the affinity of the protein–protein and protein–DNA interactions that occur in each state, and (3) whether each state is capable of transcribing. Using these components, we demonstrate how to compute a cis-regulatory function that encodes the probability of a promoter being active. Our intention is to provide enough detail so that readers with little background in thermodynamics can compose their own cis-regulatory functions. To facilitate this goal, we also describe a matrix form of the model that can be easily coded in any programming language. This formalism has great flexibility, which we show by illustrating how phenomena such as competition between transcription factors and cooperativity are readily incorporated into these models. Using this framework, we also demonstrate that Michaelis-like functions, another class of cis-regulatory models, are a subset of the thermodynamic framework with specific assumptions. By recasting Michaelis-like functions as thermodynamic functions, we emphasize the relationship between these models and delineate the specific circumstances representable by each approach. Application of thermodynamic state ensemble models is likely to be an important tool in unraveling the physical basis of combinatorial cis-regulation and in generating formalisms that accurately predict gene expression from DNA sequence. PMID:22479169

  1. Ptr-miR397a is a negative regulator of laccase genes affecting lignin content in Populus trichocarpa

    PubMed Central

    Lu, Shanfa; Li, Quanzi; Wei, Hairong; Chang, Mao-Ju; Tunlaya-Anukit, Sermsawat; Kim, Hoon; Liu, Jie; Song, Jingyuan; Sun, Ying-Hsuan; Yuan, Lichai; Yeh, Ting-Feng; Peszlen, Ilona; Ralph, John; Sederoff, Ronald R.; Chiang, Vincent L.

    2013-01-01

    Laccases, as early as 1959, were proposed to catalyze the oxidative polymerization of monolignols. Genetic evidence in support of this hypothesis has been elusive due to functional redundancy of laccase genes. An Arabidopsis double mutant demonstrated the involvement of laccases in lignin biosynthesis. We previously identified a subset of laccase genes to be targets of a microRNA (miRNA) ptr-miR397a in Populus trichocarpa. To elucidate the roles of ptr-miR397a and its targets, we characterized the laccase gene family and identified 49 laccase gene models, of which 29 were predicted to be targets of ptr-miR397a. We overexpressed Ptr-MIR397a in transgenic P. trichocarpa. In each of all nine transgenic lines tested, 17 PtrLACs were down-regulated as analyzed by RNA-seq. Transgenic lines with severe reduction in the expression of these laccase genes resulted in an ∼40% decrease in the total laccase activity. Overexpression of Ptr-MIR397a in these transgenic lines also reduced lignin content, whereas levels of all monolignol biosynthetic gene transcripts remained unchanged. A hierarchical genetic regulatory network (GRN) built by a bottom-up graphic Gaussian model algorithm provides additional support for a role of ptr-miR397a as a negative regulator of laccases for lignin biosynthesis. Full transcriptome–based differential gene expression in the overexpressed transgenics and protein domain analyses implicate previously unidentified transcription factors and their targets in an extended hierarchical GRN including ptr-miR397a and laccases that coregulate lignin biosynthesis in wood formation. Ptr-miR397a, laccases, and other regulatory components of this network may provide additional strategies for genetic manipulation of lignin content. PMID:23754401

  2. Regulation of Nitrite Stress Response in Desulfovibrio vulgaris Hildenborough, a Model Sulfate-Reducing Bacterium

    PubMed Central

    Rajeev, Lara; Chen, Amy; Kazakov, Alexey E.; Luning, Eric G.; Zane, Grant M.; Novichkov, Pavel S.; Wall, Judy D.

    2015-01-01

    ABSTRACT Sulfate-reducing bacteria (SRB) are sensitive to low concentrations of nitrite, and nitrite has been used to control SRB-related biofouling in oil fields. Desulfovibrio vulgaris Hildenborough, a model SRB, carries a cytochrome c-type nitrite reductase (nrfHA) that confers resistance to low concentrations of nitrite. The regulation of this nitrite reductase has not been directly examined to date. In this study, we show that DVU0621 (NrfR), a sigma54-dependent two-component system response regulator, is the positive regulator for this operon. NrfR activates the expression of the nrfHA operon in response to nitrite stress. We also show that nrfR is needed for fitness at low cell densities in the presence of nitrite because inactivation of nrfR affects the rate of nitrite reduction. We also predict and validate the binding sites for NrfR upstream of the nrfHA operon using purified NrfR in gel shift assays. We discuss possible roles for NrfR in regulating nitrate reductase genes in nitrate-utilizing Desulfovibrio spp. IMPORTANCE The NrfA nitrite reductase is prevalent across several bacterial phyla and required for dissimilatory nitrite reduction. However, regulation of the nrfA gene has been studied in only a few nitrate-utilizing bacteria. Here, we show that in D. vulgaris, a bacterium that does not respire nitrate, the expression of nrfHA is induced by NrfR upon nitrite stress. This is the first report of regulation of nrfA by a sigma54-dependent two-component system. Our study increases our knowledge of nitrite stress responses and possibly of the regulation of nitrate reduction in SRB. PMID:26283774

  3. Daily diaries and minority adolescents: random coefficient regression modeling of attributional style, coping, and affect.

    PubMed

    Roesch, Scott C; Vaughn, Allison A; Aldridge, Arianna A; Villodas, Feion

    2009-10-01

    Many researchers underscore the importance of coping in the daily lives of adolescents, yet very few studies measure this and related constructs at this level. Using a daily diary approach to stress and coping, the current study evaluated a series of mediational coping models in a sample of low-income minority adolescents (N = 89). Specifically, coping was hypothesized to mediate the relationship between attributional style (and dimensions) and daily affect. Using random coefficient regression modeling, the relationship between (a) the locus of causality dimension and positive affect was completely mediated by the use of acceptance and humor as coping strategies; (b) the stability dimension and positive affect was completely mediated by the use of both problem-solving and positive thinking; and (c) the stability dimension and negative affect was partially mediated by the use of religious coping. In addition, the locus of causality and stability (but not globality) dimensions were also directly related to affect. However, the relationship between pessimistic explanatory style and affect was not mediated by coping. Consistent with previous research, these findings suggest that attributions are both directly and indirectly related to indices of affect or adjustment. Thus, attributions may not only influence the type of coping strategy employed, but may also serve as coping strategies themselves. PMID:22029618

  4. A hybrid model of molecular regulation and population dynamics for yeast autophagy.

    PubMed

    Jin, Huiqin; Lei, Jinzhi

    2016-08-01

    Autophagy is an evolutionarily conserved lysosome-based degradation process that is involved in maintaining cellular homeostasis and stress responses. Dysregulation of autophagy is known to associate with many diseases. In this paper, we establish a Hybrid model of Molecular regulation and Population dynamics (HMP model) for yeast autophagy to study how autophagy regulation at molecular level affects the cell population dynamics under the stress of starvation. The model includes interactions between amino acids, TORC1, Atg1 complex, and Atg8 lipidation at the molecular level, and cell death and division at the cell behavior level. Two feedback loops are involved in autophagy induction, in which the negative feedback of TORC1 activation has been known previously, and the positive feedback between TORC1 and Atg1 complex formation is introduced according to the similarity of Drosophila and mammalian cells. We demonstrate that the two feedback loops play distinct roles in autophagy regulation. The positive feedback is pro-survival, whereas the negative feedback has little effect on the survival of population during starvation. In addition, autophagy deficient cells can be rescued from starvation by amino acid exchanges from their neighboring wild type cells. PMID:27103581

  5. Dynamic regulation of erythropoiesis: A computer model of general applicability

    NASA Technical Reports Server (NTRS)

    Leonard, J. I.

    1979-01-01

    A mathematical model for the control of erythropoiesis was developed based on the balance between oxygen supply and demand at a renal oxygen detector which controls erythropoietin release and red cell production. Feedback regulation of tissue oxygen tension is accomplished by adjustments of hemoglobin levels resulting from the output of a renal-bone marrow controller. Special consideration was given to the determinants of tissue oxygenation including evaluation of the influence of blood flow, capillary diffusivity, oxygen uptake and oxygen-hemoglobin affinity. A theoretical analysis of the overall control system is presented. Computer simulations of altitude hypoxia, red cell infusion hyperoxia, and homolytic anemia demonstrate validity of the model for general human application in health and disease.

  6. A Hybrid Model for Research on Subjective Well-Being: Examining Common- and Component-Specific Sources of Variance in Life Satisfaction, Positive Affect, and Negative Affect

    ERIC Educational Resources Information Center

    Busseri, Michael; Sadava, Stanley; DeCourville, Nancy

    2007-01-01

    The primary components of subjective well-being (SWB) include life satisfaction (LS), positive affect (PA), and negative affect (NA). There is little consensus, however, concerning how these components form a model of SWB. In this paper, six longitudinal studies varying in demographic characteristics, length of time between assessment periods,…

  7. Modelling transcriptional interference and DNA looping in gene regulation.

    PubMed

    Dodd, Ian B; Shearwin, Keith E; Sneppen, Kim

    2007-06-22

    We describe a hybrid statistical mechanical and dynamical approach for modelling the formation of closed, open and elongating complexes of RNA polymerase, the interactions of these polymerases to produce transcriptional interference, and the regulation of these processes by a DNA-binding and DNA-looping regulatory protein. As a model system, we have used bacteriophage 186, for which genetic, biochemical and structural studies have suggested that the CI repressor binds as a 14-mer to form alternative DNA-looped complexes, and activates lysogenic transcription indirectly by relieving transcriptional interference caused by the convergent lytic promoter. The modelling showed that the original mechanisms proposed to explain this relief of transcriptional interference are not consistent with the available in vivo reporter data. However, a good fit to the reporter data was given by a revised model that incorporates a novel predicted regulatory mechanism: that RNA polymerase bound at the lysogenic promoter protects itself from transcriptional interference by recruiting CI to the lytic promoter. This mechanism and various estimates of in vivo biochemical parameters for the 186 CI system should be testable. Our results demonstrate the power of mathematical modelling for the extraction of detailed biochemical information from in vivo data. PMID:17498740

  8. A modified dynamic evolving neural-fuzzy approach to modeling customer satisfaction for affective design.

    PubMed

    Kwong, C K; Fung, K Y; Jiang, Huimin; Chan, K Y; Siu, Kin Wai Michael

    2013-01-01

    Affective design is an important aspect of product development to achieve a competitive edge in the marketplace. A neural-fuzzy network approach has been attempted recently to model customer satisfaction for affective design and it has been proved to be an effective one to deal with the fuzziness and non-linearity of the modeling as well as generate explicit customer satisfaction models. However, such an approach to modeling customer satisfaction has two limitations. First, it is not suitable for the modeling problems which involve a large number of inputs. Second, it cannot adapt to new data sets, given that its structure is fixed once it has been developed. In this paper, a modified dynamic evolving neural-fuzzy approach is proposed to address the above mentioned limitations. A case study on the affective design of mobile phones was conducted to illustrate the effectiveness of the proposed methodology. Validation tests were conducted and the test results indicated that: (1) the conventional Adaptive Neuro-Fuzzy Inference System (ANFIS) failed to run due to a large number of inputs; (2) the proposed dynamic neural-fuzzy model outperforms the subtractive clustering-based ANFIS model and fuzzy c-means clustering-based ANFIS model in terms of their modeling accuracy and computational effort. PMID:24385884

  9. A Modified Dynamic Evolving Neural-Fuzzy Approach to Modeling Customer Satisfaction for Affective Design

    PubMed Central

    Kwong, C. K.; Fung, K. Y.; Jiang, Huimin; Chan, K. Y.

    2013-01-01

    Affective design is an important aspect of product development to achieve a competitive edge in the marketplace. A neural-fuzzy network approach has been attempted recently to model customer satisfaction for affective design and it has been proved to be an effective one to deal with the fuzziness and non-linearity of the modeling as well as generate explicit customer satisfaction models. However, such an approach to modeling customer satisfaction has two limitations. First, it is not suitable for the modeling problems which involve a large number of inputs. Second, it cannot adapt to new data sets, given that its structure is fixed once it has been developed. In this paper, a modified dynamic evolving neural-fuzzy approach is proposed to address the above mentioned limitations. A case study on the affective design of mobile phones was conducted to illustrate the effectiveness of the proposed methodology. Validation tests were conducted and the test results indicated that: (1) the conventional Adaptive Neuro-Fuzzy Inference System (ANFIS) failed to run due to a large number of inputs; (2) the proposed dynamic neural-fuzzy model outperforms the subtractive clustering-based ANFIS model and fuzzy c-means clustering-based ANFIS model in terms of their modeling accuracy and computational effort. PMID:24385884

  10. Affective dysfunction in a mouse model of Rett syndrome: Therapeutic effects of environmental stimulation and physical activity.

    PubMed

    Kondo, Mari A; Gray, Laura J; Pelka, Gregory J; Leang, Sook-Kwan; Christodoulou, John; Tam, Patrick P L; Hannan, Anthony J

    2016-02-01

    Rett syndrome (RTT) is a neurodevelopmental disorder associated with mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2) and consequent dysregulation of brain maturation. Patients suffer from a range of debilitating physical symptoms, however, behavioral and emotional symptoms also severely affect their quality of life. Here, we present previously unreported and clinically relevant affective dysfunction in the female heterozygous Mecp2(tm1Tam) mouse model of RTT (129sv and C57BL6 mixed background). The affective dysfunction and aberrant anxiety-related behavior of the Mecp2(+/-) mice were found to be reversible with environmental enrichment (EE) from 4 weeks of age. The effect of exercise alone (via wheel running) was also explored, providing the first evidence that increased voluntary physical activity in an animal model of RTT is beneficial for some phenotypes. Mecp2(+/-) mutants displayed elevated corticosterone despite decreased Crh expression, demonstrating hypothalamic-pituitary-adrenal axis dysregulation. EE of Mecp2(+/-) mice normalized basal serum corticosterone and hippocampal BDNF protein levels. The enrichment-induced rescue appears independent of the transcriptional regulation of the MeCP2 targets Bdnf exon 4 and Crh. These findings provide new insight into the neurodevelopmental role of MeCP2 and pathogenesis of RTT, in particular the affective dysfunction. The positive outcomes of environmental stimulation and physical exercise have implications for the development of therapies targeting the affective symptoms, as well as behavioral and cognitive dimensions, of this devastating neurodevelopmental disorder. PMID:26019053

  11. Three Independent Forms of Regulation Affect Expression of Ho, Cln1 and Cln2 during the Cell Cycle of Saccharomyces Cerevisiae

    PubMed Central

    Breeden, L.; Mikesell, G.

    1994-01-01

    The G(1) cyclins (CLNs) bind to and activate the CDC28 kinase during the G(1) to S transition in Saccharomyces cerevisiae. Two G(1) cyclins are regulated at the RNA level so that their RNAs peak at the G(1)/S boundary. In this report we show that the cell cycle regulation of CLN1 and CLN2 is partially determined by the restricted expression of SWI4, a known trans-activator of SCB elements. When SWI4 is constitutively expressed or deleted, cell cycle regulation of CLN1/2 is reduced but not eliminated. In the absence of Swi6, another known regulator of both SCB and MCB elements, cell cycle regulation of the CLNs is also reduced, and the Start-dependence of HO transcription is eliminated. This indicates that Swi6 also plays an important role in the normal cell cycle regulation of all three promoters. When both Swi6 activity and the transcriptional regulation of SWI4 are eliminated, cell cycle regulation is further reduced, indicating that these are two independent pathways of regulation. However, a twofold fluctuation in transcript levels still persists under these conditions. This reveals a third source of cell cycle control, which could affect Swi4 activity post-transcriptionally, or reflect the existence of another unidentified regulator of these promoters. PMID:7896087

  12. Modeling the Causal Regulation of Transversely Accelerated Ion (TAI) Outflows

    NASA Astrophysics Data System (ADS)

    Varney, R. H.; Wiltberger, M. J.; Zhang, B.; Schmitt, P.; Lotko, W.

    2013-12-01

    TAIs are generated by wave particle interactions driven by waves at temporal and spatial scales which are inaccessible in global coupled geospace models. So far attempts to include TAI outflows in global models have focused on the use of empirical correlations between observed outflow fluxes and various inputs such as DC Poynting flux, Alfvénic Poynting flux, and electron precipitation fluxes. These treatments ignore feedbacks between the outflow and the state of the ionosphere and assume the spatial and temporal distributions of the outflows are identical to those of their drivers. This work presents an alternative approach which can overcome these deficiencies while still being sufficiently computationally efficient to couple into a global modeling framework. TAIs are incorporated into a 3-D fluid model of the ionosphere and polar wind by modeling them as a separate fluid which obeys transport equations appropriate for monoenergetic conic distributions. The characteristics of the TAI outflow produced depend on the assumed transverse heating rates and the 'promotion rate' which connects the TAI fluid to the thermal O+ fluid. Using drivers extracted from runs of the Coupled Magnetosphere Ionosphere Thermosphere (CMIT) model, different strategies for causally regulating these free parameters are explored. The model can reproduce many of the observed features of TAI outflows but also exhibits physical attributes that empirical relationships alone miss. These characteristics include flux limiting of the outflow from below when intense outflow creates high-altitude cavities, time delays between the onset of transverse heating and the appearance of outflow, and spatial distributions of outflow which are different from the spatial distributions of the applied transverse heating and which depend on the ionospheric convection pattern.

  13. The Symbiosis Regulator CbrA Modulates a Complex Regulatory Network Affecting the Flagellar Apparatus and Cell Envelope Proteins▿ †

    PubMed Central

    Gibson, Katherine E.; Barnett, Melanie J.; Toman, Carol J.; Long, Sharon R.; Walker, Graham C.

    2007-01-01

    Sinorhizobium meliloti participates in a nitrogen-fixing symbiosis with legume plant host species of the genera Medicago, Melilotus, and Trigonella. We recently identified an S. meliloti two-component sensory histidine kinase, CbrA, which is absolutely required to establish a successful symbiosis with Medicago sativa (K. E. Gibson, G. R. Campbell, J. Lloret, and G. C. Walker, J. Bacteriol. 188:4508-4521, 2006). In addition to having a symbiotic defect, the cbrA::Tn5 mutant also has free-living phenotypes that suggest a cell envelope perturbation. Because the bases for these phenotypes are not well understood, we undertook an identification of CbrA-regulated genes. We performed a microarray analysis and compared the transcriptome of the cbrA::Tn5 mutant to that of the wild type. Our global analysis of gene expression identified 162 genes that are differentially expressed in the cbrA::Tn5 mutant, including those encoding proteins involved in motility and chemotaxis, metabolism, and cell envelope function. With regard to those genes with a known role in symbiosis, we observed increased expression of nine genes with overlapping functions in bacterial invasion of its host, which suggests that the mutant could be competent for invasion. Since these CbrA-repressed genes are vital to the invasion process, it appears that down-regulation of CbrA activity is important at this stage of nodule development. In contrast, our previous work showed that CbrA is required for bacteria to establish themselves within the host as nitrogen-fixing symbionts. Therefore, we propose a model in which CbrA functions as a developmental switch during symbiosis. PMID:17237174

  14. Regulation of mucin secretion from in vitro cellular models.

    PubMed

    Davis, C William

    2002-01-01

    Conceptually, in vitro models for airway mucin secretion may provide useful information pertinent to many aspects of goblet cell biology/physiology. Such models may be especially useful in identifying potential secretagogues, probing the distribution of receptors between goblet cell apical and basolateral membrane domains, and revealing intracellular messenger pathways underlying receptor activation. We have focused most recently on human bronchial epithelial cell cultures grown as tracheal xenografts and SPOC1 cell cultures. These two models are remarkably similar with respect to the regulation of mucin secretion: luminal challenges with the P2Y2 purinoceptor agonists ATP or UTP elicit mucin secretion with EC50s of about 3 microM and archetypal agonists to other purinoceptors test negative. P2Y2 purinoceptors typically couple via Gq to phospholipase C, suggesting that intracellular Ca2+ and protein kinase C (PKC) are important in activating intracellular pathways leading to goblet cell mucin release. Consistent with this notion, phorbol myristate acetate and ionomycin elicit mucin secretion from SPOC1 cells and HBE xenografts, whereas cyclic nucleotides do not. Delineation of the molecules comprising these receptor/messenger interactions and their supporting pathways remains an important challenge for the development of drugs effective in therapeutic interventions in mucin hypersecretory airway diseases; with these models we have initiated the process. PMID:12568491

  15. Self-perceived successful weight regulators are less affected by self-regulatory depletion in the domain of eating behavior.

    PubMed

    Friese, Malte; Engeler, Michèle; Florack, Arnd

    2015-01-01

    Weight loss and maintenance goals are highly prevalent in many affluent societies, but many weight regulators are not successful in the long term. Research started to reveal psychological mechanisms that help successful weight regulators in being successful. In the present study, we tested the assumption that these mechanisms facilitate successful self-regulation particularly under conditions of self-regulatory depletion. Participants exerted or did not exert self-control in a first task before engaging in a taste test of a tempting but unhealthy food. Participants who had initially exerted self-control ate more than participants in the control condition. This effect was reduced in self-perceived successful weight regulators as compared to perceived unsuccessful self-regulators. A reduced susceptibility to self-regulatory depletion may be an important contributor to long-term weight regulation success in successful weight regulators. PMID:25464058

  16. Confronting the outflow-regulated cluster formation model with observations

    SciTech Connect

    Nakamura, Fumitaka; Li, Zhi-Yun E-mail: zl4h@virginia.edu

    2014-03-10

    Protostellar outflows have been shown theoretically to be capable of maintaining supersonic turbulence in cluster-forming clumps and keeping the star formation rate per free-fall time as low as a few percent. We aim to test two basic predictions of this outflow-regulated cluster formation model, namely, (1) the clump should be close to virial equilibrium and (2) the turbulence dissipation rate should be balanced by the outflow momentum injection rate, using recent outflow surveys toward eight nearby cluster-forming clumps (B59, L1551, L1641N, Serpens Main Cloud, Serpens South, ρ Oph, IC 348, and NGC 1333). We find, for almost all sources, that the clumps are close to virial equilibrium and the outflow momentum injection rate exceeds the turbulence momentum dissipation rate. In addition, the outflow kinetic energy is significantly smaller than the clump gravitational energy for intermediate and massive clumps with M {sub cl} ≳ a few × 10{sup 2} M {sub ☉}, suggesting that the outflow feedback is not enough to disperse the clump as a whole. The number of observed protostars also indicates that the star formation rate per free-fall time is as small as a few percent for all clumps. These observationally based results strengthen the case for outflow-regulated cluster formation.

  17. Understanding carbon regulation in aquatic systems - Bacteriophages as a model.

    PubMed

    Sanmukh, Swapnil; Khairnar, Krishna; Paunikar, Waman; Lokhande, Satish

    2015-01-01

    The bacteria and their phages are the most abundant constituents of the aquatic environment, and so represent an ideal model for studying carbon regulation in an aquatic system. The microbe-mediated interconversion of bioavailable organic carbon (OC) into dissolved organic carbon (DOC) by the microbial carbon pump (MCP) has been suggested to have the potential to revolutionize our view of carbon sequestration. It is estimated that DOC is the largest pool of organic matter in the ocean and, though a major component of the global carbon cycle, its source is not yet well understood. A key element of the carbon cycle is the microbial conversion of DOC into inedible forms. The primary aim of this study is to understand the phage conversion from organic to inorganic carbon during phage-host interactions. Time studies of phage-host interactions under controlled conditions reveal their impact on the total carbon content of the samples and their interconversion of organic and inorganic carbon compared to control samples. A total organic carbon (TOC) analysis showed an increase in inorganic carbon content by 15-25 percent in samples with bacteria and phage compared to samples with bacteria alone. Compared to control samples, the increase in inorganic carbon content was 60-70-fold in samples with bacteria and phage, and 50-55-fold for samples with bacteria alone. This study indicates the potential impact of phages in regulating the carbon cycle of aquatic systems. PMID:26213615

  18. Understanding carbon regulation in aquatic systems - Bacteriophages as a model

    PubMed Central

    Sanmukh, Swapnil; Khairnar, Krishna; Paunikar, Waman; Lokhande, Satish

    2015-01-01

    The bacteria and their phages are the most abundant constituents of the aquatic environment, and so represent an ideal model for studying carbon regulation in an aquatic system. The microbe-mediated interconversion of bioavailable organic carbon (OC) into dissolved organic carbon (DOC) by the microbial carbon pump (MCP) has been suggested to have the potential to revolutionize our view of carbon sequestration. It is estimated that DOC is the largest pool of organic matter in the ocean and, though a major component of the global carbon cycle, its source is not yet well understood. A key element of the carbon cycle is the microbial conversion of DOC into inedible forms. The primary aim of this study is to understand the phage conversion from organic to inorganic carbon during phage-host interactions. Time studies of phage-host interactions under controlled conditions reveal their impact on the total carbon content of the samples and their interconversion of organic and inorganic carbon compared to control samples. A total organic carbon (TOC) analysis showed an increase in inorganic carbon content by 15-25 percent in samples with bacteria and phage compared to samples with bacteria alone. Compared to control samples, the increase in inorganic carbon content was 60-70-fold in samples with bacteria and phage, and 50-55-fold for samples with bacteria alone. This study indicates the potential impact of phages in regulating the carbon cycle of aquatic systems. PMID:26213615

  19. Risk analysis of nuclear safeguards regulations. [Aggregated Systems Model (ASM)

    SciTech Connect

    Al-Ayat, R.A.; Altman, W.D.; Judd, B.R.

    1982-06-01

    The Aggregated Systems Model (ASM), a probabilisitic risk analysis tool for nuclear safeguards, was applied to determine benefits and costs of proposed amendments to NRC regulations governing nuclear material control and accounting systems. The objective of the amendments was to improve the ability to detect insiders attempting to steal large quantities of special nuclear material (SNM). Insider threats range from likely events with minor consequences to unlikely events with catastrophic consequences. Moreover, establishing safeguards regulations is complicated by uncertainties in threats, safeguards performance, and consequences, and by the subjective judgments and difficult trade-offs between risks and safeguards costs. The ASM systematically incorporates these factors in a comprehensive, analytical framework. The ASM was used to evaluate the effectiveness of current safeguards and to quantify the risk of SNM theft. Various modifications designed to meet the objectives of the proposed amendments to reduce that risk were analyzed. Safeguards effectiveness was judged in terms of the probability of detecting and preventing theft, the expected time to detection, and the expected quantity of SNM diverted in a year. Data were gathered in tours and interviews at NRC-licensed facilities. The assessment at each facility was begun by carefully selecting scenarios representing the range of potential insider threats. A team of analysts and facility managers assigned probabilities for detection and prevention events in each scenario. Using the ASM we computed the measures of system effectiveness and identified cost-effective safeguards modifications that met the objectives of the proposed amendments.

  20. The Use of Gestural Modes to Enhance Expressive Conducting at All Levels of Entering Behavior through the Use of Illustrators, Affect Displays and Regulators

    ERIC Educational Resources Information Center

    Mathers, Andrew

    2009-01-01

    In this article, I discuss the use of illustrators, affect displays and regulators, which I consider to be non-verbal communication categories through which conductors can employ a more varied approach to body use, gesture and non-verbal communication. These categories employ the use of a conductor's hands and arms, face, eyes and body in a way…

  1. Computational model for the regulation of extracellular ATP and adenosine in airway epithelia.

    PubMed

    Garcia, Guilherme J M; Picher, Maryse; Zuo, Peiying; Okada, Seiko F; Lazarowski, Eduardo R; Button, Brian; Boucher, Richard C; Elston, Tim C

    2011-01-01

    Extracellular nucleotides are key components of the signaling network regulating airway clearance. They are released by the epithelium into the airway surface liquid (ASL) to stimulate cilia beating activity, mucus secretion and airway hydration. Understanding the factors affecting their availability for purinoceptor activation is an important step toward the development of new therapies for obstructive lung diseases. This chapter presents a mathematical model developed to gain predictive insights into the regulation of ASL nucleotide concentrations on human airway epithelia. The parameters were estimated from experimental data collected on polarized primary cultures of human nasal and bronchial epithelial cells. This model reproduces major experimental observations: (1) the independence of steady-state nucleotide concentrations on ASL height, (2) the impact of selective ectonucleotidase inhibitors on their steady-state ASL concentrations, (3) the changes in ASL composition caused by mechanical stress mimicking normal breathing, (4) and the differences in steady-state concentrations existing between nasal and bronchial epithelia. In addition, this model launched the study of nucleotide release into uncharted territories, which led to the discovery that airway epithelia release, not only ATP, but also ADP and AMP. This study shows that computational modeling, coupled to experimental validation, provides a powerful approach for the identification of key therapeutic targets for the improvement of airway clearance in obstructive respiratory diseases. PMID:21560044

  2. Model for how retrograde actin flow regulates adhesion traction stresses.

    PubMed

    Li, Ying; Bhimalapuram, Prabhakar; Dinner, Aaron R

    2010-05-19

    Cells from animals adhere to and exert mechanical forces on their surroundings. Cells must control these forces for many biological processes, and dysfunction can lead to pathologies. How the actions of molecules within a cell are coordinated to regulate the adhesive interaction with the extracellular matrix remains poorly understood. It has been observed that cytoplasmic proteins that link integrin cell-surface receptors with the actin cytoskeleton flow with varying rates from the leading edge toward the center of a cell. Here, we explore theoretically how measurable subcellular traction stresses depend on the local speed of retrograde actin flow. In the model, forces result from the stretching of molecular complexes in response to the drag from the flow; because these complexes break with extension-dependent kinetics, the flow results in a decrease in their number when sufficiently large. Competition between these two effects naturally gives rise to a clutch-like behavior and a nonmonotonic trend in the measured stresses, consistent with recent data for epithelial cells. We use this basic framework to evaluate slip and catch bond mechanisms for integrins; better fits of experimental data are obtained with a catch bond representation. Extension of the model to one comprising multiple molecular interfaces shifts the peak stress to higher speeds. Connections to other models and cell movement are discussed. PMID:21386439

  3. Perceived social support, hopefulness, and emotional regulations as mediators of the relationship between enacted stigma and post-traumatic growth among children affected by parental HIV/AIDS in rural China

    PubMed Central

    Wei, Wei; Li, Xiaoming; Tu, Xiaoming; Zhao, Junfeng; Zhao, Guoxiang

    2016-01-01

    ABSTRACT Some previous studies have revealed a negative impact of enacted stigma on post-traumatic growth (PTG) of children affected by HIV/AIDS, but little is known about protective psychological factors that can mitigate the effect of enacted stigma on children's PTG. This study aims to examine the mediating effects of perceived social support, hopefulness, and emotional regulation on the relationship between enacted stigma and PTG among HIV-affected children. Cross-sectional data were collected from 790 children affected by parental HIV (382 girls, 408 boys) aged 6–17 years in 2012 in rural central China. Multiple regression was conducted to test the mediation model. The study found that the experience of enacted stigma had a negative effect on PTG among children affected by HIV/AIDS. Emotional regulation together with hopefulness and perceived social support mediated the impact of enacted stigma on PTG. Perceived social support, hopefulness, and emotional regulation offer multiple levels of protection that can mitigate the impact of enacted stigma on PTG. Results suggest that future psychological intervention programs should seek strategies to reduce the stigmatizing experience of these children and promote children's level of PTG, and health professionals should also emphasize the development of these protective psychological factors. PMID:26899475

  4. School Factors Explaining Achievement on Cognitive and Affective Outcomes: Establishing a Dynamic Model of Educational Effectiveness

    ERIC Educational Resources Information Center

    Creemers, Bert; Kyriakides, Leonidas

    2010-01-01

    The dynamic model of educational effectiveness defines school level factors associated with student outcomes. Emphasis is given to the two main aspects of policy, evaluation, and improvement in schools which affect quality of teaching and learning at both the level of teachers and students: a) teaching and b) school learning environment. Five…

  5. Reactions to Stigmas among Canadian Students: Testing an Attribution-Affect-Help Judgment Model.

    ERIC Educational Resources Information Center

    Menec, Verena H.; Perry, Raymond P.

    1998-01-01

    Tests Weiner's (Bernard) attribution-affect-help judgment model in the context of nine stigmas and ascribed each to either a controllable or uncontrollable factor. Finds that higher controllability was linked to greater anger and less pity, greater pity was predictive of a greater willingness to help, and anger did not predict help judgments. (CMK)

  6. Population Validity for Educational Data Mining Models: A Case Study in Affect Detection

    ERIC Educational Resources Information Center

    Ocumpaugh, Jaclyn; Baker, Ryan; Gowda, Sujith; Heffernan, Neil; Heffernan, Cristina

    2014-01-01

    Information and communication technology (ICT)-enhanced research methods such as educational data mining (EDM) have allowed researchers to effectively model a broad range of constructs pertaining to the student, moving from traditional assessments of knowledge to assessment of engagement, meta-cognition, strategy and affect. The automated…

  7. Change in Affect and Needs Satisfaction for Amotivated Students within the Sport Education Model

    ERIC Educational Resources Information Center

    Perlman, Dana

    2010-01-01

    The purpose of this study is to examine the influence of the Sport Education Model ("SEM") on amotivated students affect and needs satisfaction. 78 amotivated students from an original pool of 1,176 students enrolled in one of 32 physical education classes. Classes were randomly assigned to either the "SEM" (N = 16)or traditional class (N = 16).…

  8. Factors Affecting Higher Order Thinking Skills of Students: A Meta-Analytic Structural Equation Modeling Study

    ERIC Educational Resources Information Center

    Budsankom, Prayoonsri; Sawangboon, Tatsirin; Damrongpanit, Suntorapot; Chuensirimongkol, Jariya

    2015-01-01

    The purpose of the research is to develop and identify the validity of factors affecting higher order thinking skills (HOTS) of students. The thinking skills can be divided into three types: analytical, critical, and creative thinking. This analysis is done by applying the meta-analytic structural equation modeling (MASEM) based on a database of…

  9. Approaching the Affective Factors of Information Seeking: The Viewpoint of the Information Search Process Model

    ERIC Educational Resources Information Center

    Savolainen, Reijo

    2015-01-01

    Introduction: The article contributes to the conceptual studies of affective factors in information seeking by examining Kuhlthau's information search process model. Method: This random-digit dial telephone survey of 253 people (75% female) living in a rural, medically under-serviced area of Ontario, Canada, follows-up a previous interview study…

  10. Parents as Role Models: Parental Behavior Affects Adolescents' Plans for Work Involvement

    ERIC Educational Resources Information Center

    Wiese, Bettina S.; Freund, Alexandra M.

    2011-01-01

    This study (N = 520 high-school students) investigates the influence of parental work involvement on adolescents' own plans regarding their future work involvement. As expected, adolescents' perceptions of parental work behavior affected their plans for own work involvement. Same-sex parents served as main role models for the adolescents' own…

  11. ERK2 protein regulates the proliferation of human mesenchymal stem cells without affecting their mobilization and differentiation potential

    SciTech Connect

    Carcamo-Orive, Ivan; Tejados, Naiara; Delgado, Jesus; Gaztelumendi, Ainhoa; Otaegui, David; Lang, Valerie; Trigueros, Cesar

    2008-05-01

    Human Mesenchymal Stem Cells (hMSC), derived mainly from adult bone marrow, are valuable models for the study of processes involved in stem cell self-renewal and differentiation. As the Extracellular signal-Regulated Kinase (ERK) signalling pathway is a major contributor to cellular growth, differentiation and survival, we have studied the functions of this kinase in hMSC activity. Ablation of ERK2 gene expression (but not ERK1) by RNA interference significantly reduced proliferation of hMSC. This reduction was due to a defect in Cyclin D1 expression and subsequent arrest in the G0/G1 phase of the cell cycle. hMSC growth is enhanced through culture medium supplementation with growth factors (GFs) such as Platelet-Derived Growth Factor (PDGF), basic Fibroblast Growth Factor (bFGF) or Epidermal Growth Factor (EGF). However, these supplements could not rescue the defect observed after ERK2 knockdown, suggesting a common signalling pathway used by these GFs for proliferation. In contrast, ERK1/2 may be dissociated from chemotactic signalling induced by the same GFs. Additionally, hMSCs were capable of differentiating into adipocytes even in the absence of either ERK1 or ERK2 proteins. Our data show that hMSCs do not require cell division to enter the adipogenic differentiation process, indicating that clonal amplification of these cells is not a critical step. However, cell-cell contact seems to be an essential requirement to be able to differentiate into mature adipocytes.

  12. Phosphorylation Affects DNA-Binding of the Senescence-Regulating bZIP Transcription Factor GBF1

    PubMed Central

    Smykowski, Anja; Fischer, Stefan M.; Zentgraf, Ulrike

    2015-01-01

    Massive changes in the transcriptome of Arabidopsis thaliana during onset and progression of leaf senescence imply a central role for transcription factors. While many transcription factors are themselves up- or down-regulated during senescence, the bZIP transcription factor G-box-binding factor 1 (GBF1/bZIP41) is constitutively expressed in Arabidopsis leaf tissue but at the same time triggers the onset of leaf senescence, suggesting posttranscriptional mechanisms for senescence-specific GBF1 activation. Here we show that GBF1 is phosphorylated by the threonine/serine CASEIN KINASE II (CKII) in vitro and that CKII phosphorylation had a negative effect on GBF1 DNA-binding to G-boxes of two direct target genes, CATALASE2 and RBSCS1a. Phosphorylation mimicry at three serine positions in the basic region of GBF1 also had a negative effect on DNA-binding. Kinase assays revealed that CKII phosphorylates at least one serine in the basic domain but has additional phosphorylation sites outside this domain. Two different ckII α subunit1 and one α subunit2 T-DNA insertion lines showed no visible senescence phenotype, but in all lines the expression of the senescence marker gene SAG12 was remarkably diminished. A model is presented suggesting that senescence-specific GBF1 activation might be achieved by lowering the phosphorylation of GBF1 by CKII. PMID:27135347

  13. p38 MAP kinase regulates the expression of XMyf5 and affects distinct myogenic programs during Xenopus development.

    PubMed

    Keren, Aviad; Bengal, Eyal; Frank, Dale

    2005-12-01

    The p38 MAPK signaling pathway is essential for skeletal muscle differentiation in tissue culture models. We demonstrate a novel role for p38 MAPK in myogenesis during early Xenopus laevis development. Interfering with p38 MAPK causes distinct defects in myogenesis. The initial expression of Myf5 is selectively blocked, while expression of MyoD is unaffected. Expression of a subset of muscle structural genes is reduced. Convergent extension movements are prevented and segmentation of the paraxial mesoderm is delayed, probably due to the failure of cells to withdraw from the cell cycle. Myotubes are properly formed; however, at later stages, they begin to degenerate, and the boundaries between somites disappear. Significant apoptotic cell death occurs in most parts of the somites. The ventral body wall muscle derived from migratory progenitor cells of the ventral somite region is poorly formed. Our data indicate that the developmental defects caused by p38alpha-knockdown were mediated by the loss of XMyf5 expression. Thus, this study identifies a specific intracellular pathway in which p38 MAPK and Myf5 proteins regulate a distinct myogenic program. PMID:16248994

  14. Mathematical analysis of a model for glucose regulation.

    PubMed

    Fessel, Kimberly; Gaither, Jeffrey B; Bower, Julie K; Gaillard, Trudy; Osei, Kwame; Rempala, Grzegorz A

    2016-02-01

    Diabetes affects millions of Americans, and the correct identification of individuals afflicted with this disease, especially of those in early stages or in progression towards diabetes, remains an active area of research. The minimal model is a simplified mathematical construct for understanding glucose-insulin interactions. Developed by Bergman, Cobelli, and colleagues over three decades ago, this system of coupled ordinary differential equations prevails as an important tool for interpreting data collected during an intravenous glucose tolerance test (IVGTT). In this study we present an explicit solution to the minimal model which allows for separating the glucose and insulin dynamics of the minimal model and for identifying patient-specific parameters of glucose trajectories from IVGTT. As illustrated with patient data, our approach seems to have an edge over more complicated methods currently used. Additionally, we also present an application of our method to prediction of the time to baseline recovery and calculation of insulin sensitivity and glucose effectiveness, two quantities regarded as significant in diabetes diagnostics. PMID:26776262

  15. miR-342-3p affects hepatocellular carcinoma cell proliferation via regulating NF-κB pathway

    SciTech Connect

    Zhao, Liang; Zhang, Yubao

    2015-02-13

    Recent research indicates that non-coding microRNAs (miRNAs) help regulate basic cellular processes in many types of cancer cells. We hypothesized that overexpression of miR-342-3p might affect proliferation of hepatocellular carcinoma (HCC) cells. After confirming overexpression of miR-342-3p with qRT-PCR, MTT assay showed that HCC cell proliferation was significantly inhibited by miR-342-3p, and that it significantly decreased BrdU-positive cell proliferation by nearly sixfold. Searching for targets using three algorithms we found that miR-342-3p is related to the NF-κB pathway and luciferase assay found that IKK-γ, TAB2 and TAB3 are miR-342-3p target genes. Results of western blot on extracted nuclear proteins of HepG2 and HCT-116 cells showed that miR-342-3p reduced and miR-342-3p-in increased p65 nuclear levels and qRT-PCR found that NF-κB pathway downstream genes were downregulated by miR-342-3p and upregulated by miR-342-3p-in, confirming that miR-342 targets NF-κB pathway. Overexpression of Ikk-γ, TAB2 and TAB3 partially rescued HCC cells proliferation inhibited by miR-342-3p. Using the GSE54751 database we evaluated expression from 10 HCC samples, which strongly suggested downregulation of miR-342-3p and we also found inverse expression between miR-342-3p and its targets IKK-γ, TAB2 and TAB3 from 71 HCC samples. Our results show that miR-342-3p has a significant role in HCC cell proliferation and is suitable for investigation of therapeutic targets. - Highlights: • MiR-342-3p suppresses hepatocellular carcinoma cell proliferation. • MiR-342-3p targets IKK-γ, TAB2 and TAB3 genes. • MiR-342-3p downregulates NF-kB signaling pathway. • MiR-342-3p is downregulated in clinical hepatocellular carcinoma samples. • The expression of miR-342-3p and its target gene is inversely related.

  16. A self-regulation resource model of self-compassion and health behavior intentions in emerging adults

    PubMed Central

    Sirois, Fuschia M.

    2015-01-01

    Objective This study tested a self-regulation resource model (SRRM) of self-compassion and health-promoting behavior intentions in emerging adults. The SRRM posits that positive and negative affect in conjunction with health self-efficacy serve as valuable self-regulation resources to promote health behaviors. Methods An online survey was completed by 403 emerging adults recruited from the community and a Canadian University in late 2008. Multiple meditation analyses with bootstrapping controlling for demographics and current health behaviors tested the proposed explanatory role of the self-regulation resource variables (affect and self-efficacy) in linking self-compassion to health behavior intentions. Results Self-compassion was positively associated with intentions to engage in health-promoting behaviors. The multiple mediation model explained 23% of the variance in health behavior intentions, with significant indirect effects through health self-efficacy and low negative affect. Conclusion Interventions aimed at increasing self-compassion in emerging adults may help promote positive health behaviors, perhaps through increasing self-regulation resources. PMID:26844074

  17. 28 CFR Appendix B to Subpart I of... - Age Distinctions in Federal Statutes or Regulations Affecting Financial Assistance Administered...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Administered by the Department of Justice Section 90.31(f) of HHS' the general regulations (45 CFR part 90... current regulations pertaining to formula grants under this statute are set forth at 28 CFR part 31 (CFDA... concerning block grants authorized under this statute are set forth at 28 CFR part 33. These...

  18. 28 CFR Appendix B to Subpart I of... - Age Distinctions in Federal Statutes or Regulations Affecting Financial Assistance Administered...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Administered by the Department of Justice Section 90.31(f) of HHS' the general regulations (45 CFR part 90... current regulations pertaining to formula grants under this statute are set forth at 28 CFR part 31 (CFDA... concerning block grants authorized under this statute are set forth at 28 CFR part 33. These...

  19. 28 CFR Appendix B to Subpart I of... - Age Distinctions in Federal Statutes or Regulations Affecting Financial Assistance Administered...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Administered by the Department of Justice Section 90.31(f) of HHS' the general regulations (45 CFR part 90... current regulations pertaining to formula grants under this statute are set forth at 28 CFR part 31 (CFDA... concerning block grants authorized under this statute are set forth at 28 CFR part 33. These...

  20. 28 CFR Appendix B to Subpart I of... - Age Distinctions in Federal Statutes or Regulations Affecting Financial Assistance Administered...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Administered by the Department of Justice Section 90.31(f) of HHS' the general regulations (45 CFR part 90... current regulations pertaining to formula grants under this statute are set forth at 28 CFR part 31 (CFDA... concerning block grants authorized under this statute are set forth at 28 CFR part 33. These...

  1. 28 CFR Appendix B to Subpart I of... - Age Distinctions in Federal Statutes or Regulations Affecting Financial Assistance Administered...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Administered by the Department of Justice Section 90.31(f) of HHS' the general regulations (45 CFR part 90... current regulations pertaining to formula grants under this statute are set forth at 28 CFR part 31 (CFDA... concerning block grants authorized under this statute are set forth at 28 CFR part 33. These...

  2. Measures of GCM Performance as Functions of Model Parameters Affecting Clouds and Radiation

    NASA Astrophysics Data System (ADS)

    Jackson, C.; Mu, Q.; Sen, M.; Stoffa, P.

    2002-05-01

    This abstract is one of three related presentations at this meeting dealing with several issues surrounding optimal parameter and uncertainty estimation of model predictions of climate. Uncertainty in model predictions of climate depends in part on the uncertainty produced by model approximations or parameterizations of unresolved physics. Evaluating these uncertainties is computationally expensive because one needs to evaluate how arbitrary choices for any given combination of model parameters affects model performance. Because the computational effort grows exponentially with the number of parameters being investigated, it is important to choose parameters carefully. Evaluating whether a parameter is worth investigating depends on two considerations: 1) does reasonable choices of parameter values produce a large range in model response relative to observational uncertainty? and 2) does the model response depend non-linearly on various combinations of model parameters? We have decided to narrow our attention to selecting parameters that affect clouds and radiation, as it is likely that these parameters will dominate uncertainties in model predictions of future climate. We present preliminary results of ~20 to 30 AMIPII style climate model integrations using NCAR's CCM3.10 that show model performance as functions of individual parameters controlling 1) critical relative humidity for cloud formation (RHMIN), and 2) boundary layer critical Richardson number (RICR). We also explore various definitions of model performance that include some or all observational data sources (surface air temperature and pressure, meridional and zonal winds, clouds, long and short-wave cloud forcings, etc...) and evaluate in a few select cases whether the model's response depends non-linearly on the parameter values we have selected.

  3. An investigation of a quantum probability model for the constructive effect of affective evaluation.

    PubMed

    White, Lee C; Barqué-Duran, Albert; Pothos, Emmanuel M

    2016-01-13

    The idea that choices can have a constructive effect has received a great deal of empirical support. The act of choosing appears to influence subsequent preferences for the options available. Recent research has proposed a cognitive model based on quantum probability (QP), which suggests that whether or not a participant provides an affective evaluation for a positively or negatively valenced stimulus can also be constructive and so, for example, influence the affective evaluation of a second oppositely valenced stimulus. However, there are some outstanding methodological questions in relation to this previous research. This paper reports the results of three experiments designed to resolve these questions. Experiment 1, using a binary response format, provides partial support for the interaction predicted by the QP model; and Experiment 2, which controls for the length of time participants have to respond, fully supports the QP model. Finally, Experiment 3 sought to determine whether the key effect can generalize beyond affective judgements about visual stimuli. Using judgements about the trustworthiness of well-known people, the predictions of the QP model were confirmed. Together, these three experiments provide further support for the QP model of the constructive effect of simple evaluations. PMID:26621993

  4. Mathematical modeling of microstructure evolution in the heat affected zone of electroslag cladding

    SciTech Connect

    Li, M.V.; Atteridge, D.G.; Meekisho, L.

    1996-12-31

    An algorithm is presented for computing microstructure evolution in weld heat affected zone of low alloy steels. It contains computational models for multicomponent Fe-C-M system equilibria, austenite grain growth kinetics, and austenite decomposition kinetics. A new kinetics model for austenite decomposition has been developed based on first principles of phase transformations expressed with Zener-Hillert type formulas. Coefficients in this model were calibrated with CCT diagrams of low alloy steels. This algorithm has the capability of computing TTT diagrams, CCT diagrams Jominy hardness curves, and phase transformations in the weld heat affected zone of low alloy steels. Excellent agreement was observed between the experimentally observed and the predicted microstructure and hardness.

  5. Accuracy of travel time distribution (TTD) models as affected by TTD complexity, observation errors, and model and tracer selection

    USGS Publications Warehouse

    Green, Christopher T.; Zhang, Yong; Jurgens, Bryant C.; Starn, J. Jeffrey; Landon, Matthew K.

    2014-01-01

    Analytical models of the travel time distribution (TTD) from a source area to a sample location are often used to estimate groundwater ages and solute concentration trends. The accuracies of these models are not well known for geologically complex aquifers. In this study, synthetic datasets were used to quantify the accuracy of four analytical TTD models as affected by TTD complexity, observation errors, model selection, and tracer selection. Synthetic TTDs and tracer data were generated from existing numerical models with complex hydrofacies distributions for one public-supply well and 14 monitoring wells in the Central Valley, California. Analytical TTD models were calibrated to synthetic tracer data, and prediction errors were determined for estimates of TTDs and conservative tracer (NO3−) concentrations. Analytical models included a new, scale-dependent dispersivity model (SDM) for two-dimensional transport from the watertable to a well, and three other established analytical models. The relative influence of the error sources (TTD complexity, observation error, model selection, and tracer selection) depended on the type of prediction. Geological complexity gave rise to complex TTDs in monitoring wells that strongly affected errors of the estimated TTDs. However, prediction errors for NO3− and median age depended more on tracer concentration errors. The SDM tended to give the most accurate estimates of the vertical velocity and other predictions, although TTD model selection had minor effects overall. Adding tracers improved predictions if the new tracers had different input histories. Studies using TTD models should focus on the factors that most strongly affect the desired predictions.

  6. Models of professional regulation: institutionalizing an agency relationship

    PubMed Central

    2013-01-01

    The regulation of medical practice can historically be understood as a second-level agency relationship whereby the state delegated authority to professional bodies to police the primary agency relationship between the individual physician and the patient. Borow, Levi and Glekin show how different national systems vary in the degree to which they insist on institutionally insulating the agency function from the promotion of private professional interests, and relate these variations to different models of the health care state. In fact these differences have even deeper roots in different “liberal” or “coordinated” varieties of capitalist political economies. Neither model is inherently more efficient than the other: what matters is the internal coherence or logic of these systems that conditions the expectations of actors in responding to particular challenges. The territory that Borow, Levi and Glekin have usefully mapped invites further exploration in this regard. This is a commentary on http://www.ijhpr.org/content/2/1/8. PMID:23537144

  7. Functional imaging studies of emotion regulation: A synthetic review and evolving model of the cognitive control of emotion

    PubMed Central

    Ochsner, Kevin N.; Silvers, Jennifer A.; Buhle, Jason T.

    2014-01-01

    This paper reviews and synthesizes functional imaging research that over the past decade has begun to offer new insights into the brain mechanisms underlying emotion regulation. Towards that end, the first section of the paper outlines a model of the processes and neural systems involved in emotion generation and regulation. The second section surveys recent research supporting and elaborating the model, focusing primarily on studies of the most commonly investigated strategy, which is known as reappraisal. At its core, the model specifies how prefrontal and cingulate control systems modulate activity in perceptual, semantic and affect systems as a function of one's regulatory goals, tactics, and the nature of the stimuli and emotions being regulated. This section also shows how the model can be generalized to understand the brain mechanisms underlying other emotion regulation strategies as well as a range of other allied phenomena. The third and last section considers directions for future research, including how basic models of emotion regulation can be translated to understand changes in emotion across the lifespan and in clinical disorders. PMID:23025352

  8. Modeling of Large Methane Releases and their affect on the Chemistry of the Atmosphere

    NASA Astrophysics Data System (ADS)

    Bergmann, D. J.; Cameron-Smith, P. J.; Elliot, S.; Reagan, M. T.; Maltrud, M. E.

    2009-12-01

    A vast quantity of methane is locked in solid phase as methane clathrates in ocean sediments (as much carbon as all other fossil fuels combined). Rapid destabilization of the clathrates due to climate warming would significantly increase methane emissions from the ocean. This would result in a number of affects including strong greenhouse heating, increased surface ozone, reduced stratospheric ozone, and intensification of the ozone hole. Many of the affects in the chemistry of the atmosphere are non-linear and difficult to estimate without a detailed model. As part of the DOE IMPACTS project on abrupt climate change we have used our 3D global atmospheric chemistry model (IMPACT) to take a first look at some of these affects. This model includes detailed chemistry of the troposphere (including isoprene and other hydrocarbons) and the stratosphere (including the important chlorine and bromine compounds). We ran the model at 4x5 degree resolution with methane simply scaled to present day emissions. We show results for 1x, 2x, 10x, 100x, and 1000x emission scenarios. We analyzed the results after the simulations have reached steady state (many years of simulation) and show the affect of these large releases on tropospheric air quality, the “health” of the stratosphere, and greenhouse heating. Substantial increases were seen in atmospheric methane lifetime, a positive feedback, due to the increased methane reducing the OH concentration. In the future we will couple our atmospheric chemistry to a complete Earth system model (based on CCSM) for methane including ocean ecosystem, ocean sediment and boreal land models to give more accurate estimates of the emission term and to look at the full system response.

  9. Sensitivity analysis of a global aerosol model to understand how parametric uncertainties affect model predictions

    NASA Astrophysics Data System (ADS)

    Lee, L. A.; Carslaw, K. S.; Pringle, K. J.

    2012-04-01

    Global aerosol contributions to radiative forcing (and hence climate change) are persistently subject to large uncertainty in successive Intergovernmental Panel on Climate Change (IPCC) reports (Schimel et al., 1996; Penner et al., 2001; Forster et al., 2007). As such more complex global aerosol models are being developed to simulate aerosol microphysics in the atmosphere. The uncertainty in global aerosol model estimates is currently estimated by measuring the diversity amongst different models (Textor et al., 2006, 2007; Meehl et al., 2007). The uncertainty at the process level due to the need to parameterise in such models is not yet understood and it is difficult to know whether the added model complexity comes at a cost of high model uncertainty. In this work the model uncertainty and its sources due to the uncertain parameters is quantified using variance-based sensitivity analysis. Due to the complexity of a global aerosol model we use Gaussian process emulation with a sufficient experimental design to make such as a sensitivity analysis possible. The global aerosol model used here is GLOMAP (Mann et al., 2010) and we quantify the sensitivity of numerous model outputs to 27 expertly elicited uncertain model parameters describing emissions and processes such as growth and removal of aerosol. Using the R package DiceKriging (Roustant et al., 2010) along with the package sensitivity (Pujol, 2008) it has been possible to produce monthly global maps of model sensitivity to the uncertain parameters over the year 2008. Global model outputs estimated by the emulator are shown to be consistent with previously published estimates (Spracklen et al. 2010, Mann et al. 2010) but now we have an associated measure of parameter uncertainty and its sources. It can be seen that globally some parameters have no effect on the model predictions and any further effort in their development may be unnecessary, although a structural error in the model might also be identified. The

  10. A kinetic model of TBP auto-regulation exhibits bistability

    PubMed Central

    2010-01-01

    Background TATA Binding Protein (TBP) is required for transcription initiation by all three eukaryotic RNA polymerases. It participates in transcriptional initiation at the majority of eukaryotic gene promoters, either by direct association to the TATA box upstream of the transcription start site or by indirectly localizing to the promoter through other proteins. TBP exists in solution in a dimeric form but binds to DNA as a monomer. Here, we present the first mathematical model for auto-catalytic TBP expression and use it to study the role of dimerization in maintaining the steady state TBP level. Results We show that the autogenous regulation of TBP results in a system that is capable of exhibiting three steady states: an unstable low TBP state, one stable state corresponding to a physiological TBP concentration, and another stable steady state corresponding to unviable cells where no TBP is expressed. Our model predicts that a basal level of TBP is required to establish the transcription of the TBP gene, and hence for cell viability. It also predicts that, for the condition corresponding to a typical mammalian cell, the high-TBP state and cell viability is sensitive to variation in DNA binding strength. We use the model to explore the effect of the dimer in buffering the response to changes in TBP levels, and show that for some physiological conditions the dimer is not important in buffering against perturbations. Conclusions Results on the necessity of a minimum basal TBP level support the in vivo observations that TBP is maternally inherited, providing the small amount of TBP required to establish its ubiquitous expression. The model shows that the system is sensitive to variations in parameters indicating that it is vulnerable to mutations in TBP. A reduction in TBP-DNA binding constant can lead the system to a regime where the unviable state is the only steady state. Contrary to the current hypotheses, we show that under some physiological conditions the

  11. The beta-ketoadipate pathway of Acinetobacter baylyi undergoes carbon catabolite repression, cross-regulation and vertical regulation, and is affected by Crc.

    PubMed

    Bleichrodt, Fenja S; Fischer, Rita; Gerischer, Ulrike C

    2010-05-01

    The degradation of many structurally diverse aromatic compounds in Acinetobacter baylyi is accomplished by the beta-ketoadipate pathway. In addition to specific induction of expression by certain aromatic compounds, this pathway is regulated by complex mechanisms at multiple levels, which are the topic of this study. Multiple operons feeding into the beta-ketoadipate pathway are controlled by carbon catabolite repression (CCR) caused by succinate plus acetate. The pathways under study enable the catabolism of benzoate (ben), catechol (catA), cis,cis-muconate (catB,C,I,J,F,D), vanillate (van), hydroxycinnamates (hca), dicarboxylates (dca), salicylate (sal), anthranilate (ant) and benzyl esters (are). For analysis of CCR at the transcriptional level a luciferase reporter gene cassette was introduced into the operons. The Crc (catabolite repression control) protein is involved in repression of all operons (except for catA), as demonstrated by the analysis of respective crc strains. In addition, cross-regulation was demonstrated for the vanA,B, hca and dca operons. The presence of protocatechuate caused transcriptional repression of the vanA,B- and hca-encoded funnelling pathways (vertical regulation). Thus the results presented extend the understanding both of CCR and of the effects of Crc for all aromatic degradative pathways of A. baylyi and increase the number of operons known to be controlled by two additional mechanisms, cross-regulation and vertical regulation. PMID:20110298

  12. CRNDE affects the malignant biological characteristics of human glioma stem cells by negatively regulating miR-186

    PubMed Central

    Zheng, Jian; Li, Xiao-dong; Wang, Ping; Liu, Xiao-bai; Xue, Yi-xue; Hu, Yi; Li, Zhen; Li, Zhi-qing; Wang, Zhen-hua; Liu, Yun-hui

    2015-01-01

    The long non-coding RNA Colorectal neoplasia differentially expressed (CRNDE) is a novel gene that activated early in colorectal neoplasia, but it is also up-regulated in many other solid tumors. Herein, the function and underlying mechanism of CRNDE in regulating glioma stem cells (GSCs) were investigated. We found that CRNDE expression was up-regulated while miR-186 expression was down-regulated in GSCs. Overexpression of CRNDE could promote the cellular proliferation, migration, invasion and inhibit the apoptosis in GSCs. Overexpression of miR-186 exerted functions of inhibiting the proliferation, migration and invasion of GSCs and promoting apoptosis. And CRNDE decreased the expression levels of XIAP and PAK7 by binding to miR-186 and negatively regulating it. In addition, miR-186 binded to XIAP and PAK7 3′UTR region, and decrease the expression of them, thus regulating the expression levels of downstream target proteins such as caspase 3, BAD, cyclin D1 and MARK2. The in vivo effect of CRNDE and miR-186 showed that the tumor formation rate was minimum in tumor-bearing nude mice with the knockdown of CRNDE and the overexpression of miR-186. In conclusion, CRNDE played an oncogenic role of GSCs through the negative regulation of miR-186. Both CRNDE and miR-186 could be regarded as potential targets in the glioma therapy. PMID:26231038

  13. Soil microbes and plant invasions—how soil-borne pathogens regulate plant populations and affect plant invasions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exotic plant invaders are a major global threat to biodiversity and ecosystem function. Here I present multiple lines of evidence suggesting that soil microbial communities affect the population growth rates of Prunus serotina in its native range and affect its invasiveness abroad. Research often ...

  14. Novel TetR family transcriptional factor regulates expression of multiple transport-related genes and affects rifampicin resistance in Mycobacterium smegmatis

    PubMed Central

    Liu, Huicong; Yang, Min; He, Zheng-Guo

    2016-01-01

    Transport-related genes significantly affect bacterial antibiotic resistance. However, the effects of these genes and their regulation of bacterial drug resistance in several mycobacterial species, including the fast-growing Mycobacterium smegmatis, the pathogen M. tuberculosis and M. avium have not been clearly characterized. We identified Ms4022 (MSMEG_4022) as a novel TetR family regulator that activates the expression of seven transport-related genes and affects drug resistance in M. smegmatis. Overexpression of Ms4022 inhibited M. smegmatis growth and enhanced mycobacterial resistance to the anti-tuberculosis drug rifampicin (RIF). By contrast, the Ms4022-deleted mycobacterial strain has shown sensitive to RIF. Ms4022 recognized three 19 bp non-palindromic motifs containing a 9 bp conserved region at their 5′ end and it directly regulated seven transport-related genes, which affects mycobacterial resistance to RIF. Overexpression of three of seven transport-related genes (Ms1448, Ms1613, and Ms5278) inhibited the growth of M. smegmatis. This study improves our understanding of the function of mycobacterial transport-related genes and their regulation of bacterial drug resistance. PMID:27271013

  15. Novel TetR family transcriptional factor regulates expression of multiple transport-related genes and affects rifampicin resistance in Mycobacterium smegmatis.

    PubMed

    Liu, Huicong; Yang, Min; He, Zheng-Guo

    2016-01-01

    Transport-related genes significantly affect bacterial antibiotic resistance. However, the effects of these genes and their regulation of bacterial drug resistance in several mycobacterial species, including the fast-growing Mycobacterium smegmatis, the pathogen M. tuberculosis and M. avium have not been clearly characterized. We identified Ms4022 (MSMEG_4022) as a novel TetR family regulator that activates the expression of seven transport-related genes and affects drug resistance in M. smegmatis. Overexpression of Ms4022 inhibited M. smegmatis growth and enhanced mycobacterial resistance to the anti-tuberculosis drug rifampicin (RIF). By contrast, the Ms4022-deleted mycobacterial strain has shown sensitive to RIF. Ms4022 recognized three 19 bp non-palindromic motifs containing a 9 bp conserved region at their 5' end and it directly regulated seven transport-related genes, which affects mycobacterial resistance to RIF. Overexpression of three of seven transport-related genes (Ms1448, Ms1613, and Ms5278) inhibited the growth of M. smegmatis. This study improves our understanding of the function of mycobacterial transport-related genes and their regulation of bacterial drug resistance. PMID:27271013

  16. A mediational model of trait negative affectivity, dispositional thought suppression, and intrusive thoughts following laboratory stressors.

    PubMed

    Lynch, Thomas R; Schneider, Kristin G; Rosenthal, M Zachary; Cheavens, Jennifer S

    2007-04-01

    Two studies examined the relationships among trait negative affectivity, dispositional thought suppression, and intrusions in non-clinical samples. In Study 1 (N=87), participants were presented with a series of emotionally evocative images and intrusions were examined 48 h after presentation via self-report. In Study 2 (N=118), intrusions were examined using a behavioral Key-press and self-report at two time points (5 and 20 min) following exposure to a series of emotionally evocative images. In each study, participants were assessed for trait negative affectivity and the tendency to engage in thought suppression in response to unpleasant cognitions. Results from both studies support a model in which chronic thought suppression fully mediates the relationship between negative affectivity and the frequency of intrusions. PMID:16934744

  17. Global self-esteem in relation to structural models of personality and affectivity.

    PubMed

    Watson, David; Suls, Jerry; Haig, Jeffrey

    2002-07-01

    Three studies examined global self-esteem in relation to structural models of personality and affectivity. In every study, self-esteem was strongly negatively correlated with Neuroticism/Negative Affectivity and moderately to strongly related to Extraversion/Positive Affectivity. Additional findings, however, revealed that self-esteem is better viewed at the lower order level. For instance, global self-esteem correlated -.79 with the Depression facet of the Revised NEO Personality Inventory (P. T. Costa, Jr., & R. R. McCrae, 1992) in Study 3. Moreover, confirmatory factor analyses produced very strong correlations between self-esteem and depression in both Study 2 (r = -.82) and Study 3 (r = -.86). Taken together, the data suggest that global self-esteem measures define one end of a bipolar continuum, with trait indicators of depression defining the other. PMID:12088125

  18. Mathematical model with spatially uniform regulation explains long-range bidirectional transport of early endosomes in fungal hyphae.

    PubMed

    Gou, Jia; Edelstein-Keshet, Leah; Allard, Jun

    2014-08-15

    In many cellular contexts, cargo is transported bidirectionally along microtubule bundles by dynein and kinesin-family motors. Upstream factors influence how individual cargoes are locally regulated, as well as how long-range transport is regulated at the whole-cell scale. Although the details of local, single-cargo bidirectional switching have been extensively studied, it remains to be elucidated how this results in cell-scale spatial organization. Here we develop a mathematical model of early endosome transport in Ustilago maydis. We demonstrate that spatiotemporally uniform regulation, with constant transition rates, results in cargo dynamics that is consistent with experimental data, including data from motor mutants. We find that microtubule arrays can be symmetric in plus-end distribution but asymmetric in binding-site distribution in a manner that affects cargo dynamics and that cargo can travel past microtubule ends in microtubule bundles. Our model makes several testable predictions, including secondary features of dynein and cargo distributions. PMID:24943842

  19. The EMO-Model: An Agent-Based Model of Primate Social Behavior Regulated by Two Emotional Dimensions, Anxiety-FEAR and Satisfaction-LIKE

    PubMed Central

    Evers, Ellen; de Vries, Han; Spruijt, Berry M.; Sterck, Elisabeth H. M.

    2014-01-01

    Agent-based models provide a promising tool to investigate the relationship between individuals’ behavior and emerging group-level patterns. An individual’s behavior may be regulated by its emotional state and its interaction history with specific individuals. Emotional bookkeeping is a candidate mechanism to keep track of received benefits from specific individuals without requiring high cognitive abilities. However, how this mechanism may work is difficult to study in real animals, due to the complexity of primate social life. To explore this theoretically, we introduce an agent-based model, dubbed EMO-model, in which we implemented emotional bookkeeping. In this model the social behaviors of primate-like individuals are regulated by emotional processes along two dimensions. An individual’s emotional state is described by an aversive and a pleasant dimension (anxiety and satisfaction) and by its activating quality (arousal). Social behaviors affect the individuals’ emotional state. To implement emotional bookkeeping, the receiver of grooming assigns an accumulated affiliative attitude (LIKE) to the groomer. Fixed partner-specific agonistic attitudes (FEAR) reflect the stable dominance relations between group members. While the emotional state affects an individual’s general probability of executing certain behaviors, LIKE and FEAR affect the individual’s partner-specific behavioral probabilities. In this way, emotional processes regulate both spontaneous behaviors and appropriate responses to received behaviors, while emotional bookkeeping via LIKE attitudes regulates the development and maintenance of affiliative relations. Using an array of empirical data, the model processes were substantiated and the emerging model patterns were partially validated. The EMO-model offers a framework to investigate the emotional bookkeeping hypothesis theoretically and pinpoints gaps that need to be investigated empirically. PMID:24504194

  20. Using representations in geometry: a model of students' cognitive and affective performance

    NASA Astrophysics Data System (ADS)

    Panaoura, Areti

    2014-05-01

    Self-efficacy beliefs in mathematics, as a dimension of the affective domain, are related with students' performance on solving tasks and mainly on overcoming cognitive obstacles. The present study investigated the interrelations of cognitive performance on geometry and young students' self-efficacy beliefs about using representations for solving geometrical tasks. The emphasis was on confirming a theoretical model for the primary-school and secondary-school students and identifying the differences and similarities for the two ages. A quantitative study was developed and data were collected from 1086 students in Grades 5-8. Confirmatory factor analysis affirmed the existence of a coherent model of affective dimensions about the use of representations for understanding the geometrical concepts, which becomes more stable across the educational levels.

  1. Children affected by HIV/AIDS: SAFE, a model for promoting their security, health, and development.

    PubMed

    Betancourt, Theresa S; Fawzi, Mary K S; Bruderlein, Claude; Desmond, Chris; Kim, Jim Y

    2010-05-01

    A human security framework posits that individuals are the focus of strategies that protect the safety and integrity of people by proactively promoting children's well being, placing particular emphasis on prevention efforts and health promotion. This article applies this framework to a rights-based approach in order to examine the health and human rights of children affected by HIV/AIDS. The SAFE model describes sources of insecurity faced by children across four fundamental dimensions of child well-being and the survival strategies that children and families may employ in response. The SAFE model includes: Safety/protection; Access to health care and basic physiological needs; Family/connection to others; and Education/livelihoods. We argue that it is critical to examine the situation of children through an integrated lens that effectively looks at human security and children's rights through a holistic approach to treatment and care rather than artificially limiting our scope of work to survival-oriented interventions for children affected by HIV/AIDS. Interventions targeted narrowly at children, in isolation of their social and communal environment as outlined in the SAFE model, may in fact undermine protective resources in operation in families and communities and present additional threats to children's basic security. An integrated approach to the basic security and care of children has implications for the prospects of millions of children directly infected or indirectly affected by HIV/AIDS around the world. The survival strategies that young people and their families engage in must be recognized as a roadmap for improving their protection and promoting healthy development. Although applied to children affected by HIV/AIDS in the present analysis, the SAFE model has implications for guiding the care and protection of children and families facing adversity due to an array of circumstances from armed conflict and displacement to situations of extreme poverty

  2. Bioelectrical regulation of cell cycle and the planarian model system.

    PubMed

    Barghouth, Paul G; Thiruvalluvan, Manish; Oviedo, Néstor J

    2015-10-01

    Cell cycle regulation through the manipulation of endogenous membrane potentials offers tremendous opportunities to control cellular processes during tissue repair and cancer formation. However, the molecular mechanisms by which biophysical signals modulate the cell cycle remain underappreciated and poorly understood. Cells in complex organisms generate and maintain a constant voltage gradient across the plasma membrane known as the transmembrane potential. This potential, generated through the combined efforts of various ion transporters, pumps and channels, is known to drive a wide range of cellular processes such as cellular proliferation, migration and tissue regeneration while its deregulation can lead to tumorigenesis. These cellular regulatory events, coordinated by ionic flow, correspond to a new and exciting field termed molecular bioelectricity. We aim to present a brief discussion on the biophysical machinery involving membrane potential and the mechanisms mediating cell cycle progression and cancer transformation. Furthermore, we present the planarian Schmidtea mediterranea as a tractable model system for understanding principles behind molecular bioelectricity at both the cellular and organismal level. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. PMID:25749155

  3. Have changes to meat and poultry food safety regulation in Australia affected the prevalence of Salmonella or of salmonellosis?

    PubMed

    Sumner, John; Raven, Geoff; Givney, Rod

    2004-04-15

    During the 1990s, there was radical change in regulation of meat and poultry hygiene in Australia, and Australian Standards were developed for each sector of the meat industry. Systems for industry/government co-regulation and company-employed meat inspection were introduced based on company HACCP programs approved and audited by the Controlling Authority. However, in the 5 years since regulatory changes took full effect, rates of salmonellosis have not decreased (surveillance and reporting systems have remained unchanged). Using statistics gathered by the National Enteric Pathogens Surveillance Scheme, an attempt was made to link Salmonella serovars isolated from meat and poultry with those causing salmonellosis. Two periods were studied, 1993/1994, before regulations were introduced, and 2000/2001, when regulations should be having an effect. For red meat, the same serovars were prominent among the top 10 isolates both before and after regulation, and there was little linkage with salmonelloses. For poultry, frequently isolated serovars differed pre- and post-regulation, however, in both periods there was some linkage between serovars isolated from poultry and those causing salmonelloses. Using published and unpublished survey data, it was concluded that there had been improvements in microbiological quality of red meat and poultry over the same timeframe as regulatory changes. That these improvements apparently have not carried through to reduced case-rates for salmonellosis may be due to numerous causes, including lack of control in the food processing, food service and home sectors. The present paper illustrates difficulties faced by governments in measuring public health outcomes of changes to food hygiene regulation. PMID:15109797

  4. Using Bayesian Nonparametric Hidden Semi-Markov Models to Disentangle Affect Processes during Marital Interaction

    PubMed Central

    Griffin, William A.; Li, Xun

    2016-01-01

    Sequential affect dynamics generated during the interaction of intimate dyads, such as married couples, are associated with a cascade of effects—some good and some bad—on each partner, close family members, and other social contacts. Although the effects are well documented, the probabilistic structures associated with micro-social processes connected to the varied outcomes remain enigmatic. Using extant data we developed a method of classifying and subsequently generating couple dynamics using a Hierarchical Dirichlet Process Hidden semi-Markov Model (HDP-HSMM). Our findings indicate that several key aspects of existing models of marital interaction are inadequate: affect state emissions and their durations, along with the expected variability differences between distressed and nondistressed couples are present but highly nuanced; and most surprisingly, heterogeneity among highly satisfied couples necessitate that they be divided into subgroups. We review how this unsupervised learning technique generates plausible dyadic sequences that are sensitive to relationship quality and provide a natural mechanism for computational models of behavioral and affective micro-social processes. PMID:27187319

  5. Using Bayesian Nonparametric Hidden Semi-Markov Models to Disentangle Affect Processes during Marital Interaction.

    PubMed

    Griffin, William A; Li, Xun

    2016-01-01

    Sequential affect dynamics generated during the interaction of intimate dyads, such as married couples, are associated with a cascade of effects-some good and some bad-on each partner, close family members, and other social contacts. Although the effects are well documented, the probabilistic structures associated with micro-social processes connected to the varied outcomes remain enigmatic. Using extant data we developed a method of classifying and subsequently generating couple dynamics using a Hierarchical Dirichlet Process Hidden semi-Markov Model (HDP-HSMM). Our findings indicate that several key aspects of existing models of marital interaction are inadequate: affect state emissions and their durations, along with the expected variability differences between distressed and nondistressed couples are present but highly nuanced; and most surprisingly, heterogeneity among highly satisfied couples necessitate that they be divided into subgroups. We review how this unsupervised learning technique generates plausible dyadic sequences that are sensitive to relationship quality and provide a natural mechanism for computational models of behavioral and affective micro-social processes. PMID:27187319

  6. Comparing Models for Generating a System of Activation and Inhibition of Self-Regulated Learning

    ERIC Educational Resources Information Center

    Magno, Carlo

    2008-01-01

    The study investigated the effect of activation and negative affect on self-regulation. The activation factors are self-determination, disengagement, initiative, and persistence while negative affect is composed of worry, anxiety, thought suppression, and fear of negative evaluation. Separate measures were used for each factor and administered to…

  7. Inactivation of the LysR regulator Cj1000 of Campylobacter jejuni affects host colonization and respiration.

    PubMed

    Dufour, Virginie; Li, Jennifer; Flint, Annika; Rosenfeld, Eric; Rivoal, Katell; Georgeault, Sylvie; Alazzam, Bachar; Ermel, Gwennola; Stintzi, Alain; Bonnaure-Mallet, Martine; Baysse, Christine

    2013-06-01

    Transcriptional regulation mediates adaptation of pathogens to environmental stimuli and is important for host colonization. The Campylobacter jejuni genome sequence reveals a surprisingly small set of regulators, mostly of unknown function, suggesting an intricate regulatory network. Interestingly, C. jejuni lacks the homologues of ubiquitous regulators involved in stress response found in many other Gram-negative bacteria. Nonetheless, cj1000 is predicted to encode the sole LysR-type regulator in the C. jejuni genome, and thus may be involved in major adaptation pathways. A cj1000 mutant strain was constructed and found to be attenuated in its ability to colonize 1-day-old chicks. Complementation of the cj1000 mutation restored the colonization ability to wild-type levels. The mutant strain was also outcompeted in a competitive colonization assay of the piglet intestine. Oxygraphy was carried out for what is believed to be the first time with the Oroboros Oxygraph-2k on C. jejuni and revealed a role for Cj1000 in controlling O2 consumption. Furthermore, microarray analysis of the cj1000 mutant revealed both direct and indirect regulatory targets, including genes involved in energy metabolism and oxidative stress defences. These results highlight the importance of Cj1000 regulation in host colonization and in major physiological pathways. PMID:23558264

  8. Inferring transcriptional gene regulation network of starch metabolism in Arabidopsis thaliana leaves using graphical Gaussian model

    PubMed Central

    2012-01-01

    Background Starch serves as a temporal storage of carbohydrates in plant leaves during day/night cycles. To study transcriptional regulatory modules of this dynamic metabolic process, we conducted gene regulation network analysis based on small-sample inference of graphical Gaussian model (GGM). Results Time-series significant analysis was applied for Arabidopsis leaf transcriptome data to obtain a set of genes that are highly regulated under a diurnal cycle. A total of 1,480 diurnally regulated genes included 21 starch metabolic enzymes, 6 clock-associated genes, and 106 transcription factors (TF). A starch-clock-TF gene regulation network comprising 117 nodes and 266 edges was constructed by GGM from these 133 significant genes that are potentially related to the diurnal control of starch metabolism. From this network, we found that β-amylase 3 (b-amy3: At4g17090), which participates in starch degradation in chloroplast, is the most frequently connected gene (a hub gene). The robustness of gene-to-gene regulatory network was further analyzed by TF binding site prediction and by evaluating global co-expression of TFs and target starch metabolic enzymes. As a result, two TFs, indeterminate domain 5 (AtIDD5: At2g02070) and constans-like (COL: At2g21320), were identified as positive regulators of starch synthase 4 (SS4: At4g18240). The inference model of AtIDD5-dependent positive regulation of SS4 gene expression was experimentally supported by decreased SS4 mRNA accumulation in Atidd5 mutant plants during the light period of both short and long day conditions. COL was also shown to positively control SS4 mRNA accumulation. Furthermore, the knockout of AtIDD5 and COL led to deformation of chloroplast and its contained starch granules. This deformity also affected the number of starch granules per chloroplast, which increased significantly in both knockout mutant lines. Conclusions In this study, we utilized a systematic approach of microarray analysis to discover

  9. P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression

    PubMed Central

    Zhang, E-b; Yin, D-d; Sun, M; Kong, R; Liu, X-h; You, L-h; Han, L; Xia, R; Wang, K-m; Yang, J-s; De, W; Shu, Y-q; Wang, Z-x

    2014-01-01

    Recently, a novel class of transcripts, long non-coding RNAs (lncRNAs), is being identified at a rapid pace. These RNAs have critical roles in diverse biological processes, including tumorigenesis. Here we report that taurine-upregulated gene 1 (TUG1), a 7.1-kb lncRNA, recruiting and binding to polycomb repressive complex 2 (PRC2), is generally downregulated in non-small cell lung carcinoma (NSCLC) tissues. In a cohort of 192 NSCLC patients, the lower expression of TUG1 was associated with a higher TNM stage and tumor size, as well as poorer overall survival (P<0.001). Univariate and multivariate analyses revealed that TUG1 expression serves as an independent predictor for overall survival (P<0.001). Further experiments revealed that TUG1 expression was induced by p53, and luciferase and chromatin immunoprecipitation (ChIP) assays confirmed that TUG1 was a direct transcriptional target of p53. TUG1 knockdown significantly promoted the proliferation in vitro and in vivo. Moreover, the lncRNA-mediated regulation of the expression of HOX genes in tumorigenesis and development has been recently receiving increased attention. Interestingly, inhibition of TUG1 could upregulate homeobox B7 (HOXB7) expression; ChIP assays demonstrated that the promoter of HOXB7 locus was bound by EZH2 (enhancer of zeste homolog 2), a key component of PRC2, and was H3K27 trimethylated. This TUG1-mediated growth regulation is in part due to specific modulation of HOXB7, thus participating in AKT and MAPK pathways. Together, these results suggest that p53-regulated TUG1 is a growth regulator, which acts in part through control of HOXB7. The p53/TUG1/PRC2/HOXB7 interaction might serve as targets for NSCLC diagnosis and therapy. PMID:24853421

  10. Loss of the Response Regulator CtrA Causes Pleiotropic Effects on Gene Expression but Does Not Affect Growth Phase Regulation in Rhodobacter capsulatus

    SciTech Connect

    Mercer, Ryan; Callister, Stephen J.; Lipton, Mary S.; Pasa-Tolic, Ljiljana; Strnad, Hynek; Paces, Vaclav; Beatty, J. T.; Lang, Andrew S.

    2010-06-01

    The purple non-sulfur bacterium Rhodobacter capsulatus has been extensively studied for its diverse metabolic capabilities, as well as for its production of a Gene Transfer Agent (RcGTA). Production of RcGTA requires the response regulator protein CtrA. We have used whole genome transcript and whole cell proteome analyses of wild type and ctrA mutant cultures to completely characterize the regulatory role of CtrA in R. capsulatus.

  11. SAD-B kinase regulates pre-synaptic vesicular dynamics at hippocampal Schaffer collateral synapses and affects contextual fear memory.

    PubMed

    Watabe, Ayako M; Nagase, Masashi; Hagiwara, Akari; Hida, Yamato; Tsuji, Megumi; Ochiai, Toshitaka; Kato, Fusao; Ohtsuka, Toshihisa

    2016-01-01

    Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, such as axon specifications and maturation in central and peripheral nervous systems. At mature pre-synaptic terminals, SAD-B is associated with synaptic vesicles and the active zone cytomatrix; however, how SAD-B regulates neurotransmission and synaptic plasticity in vivo remains unclear. Thus, we used SAD-B knockout (KO) mice to study the function of this pre-synaptic kinase in the brain. We found that the paired-pulse ratio was significantly enhanced at Shaffer collateral synapses in the hippocampal CA1 region in SAD-B KO mice compared with wild-type littermates. We also found that the frequency of the miniature excitatory post-synaptic current was decreased in SAD-B KO mice. Moreover, synaptic depression following prolonged low-frequency synaptic stimulation was significantly enhanced in SAD-B KO mice. These results suggest that SAD-B kinase regulates vesicular release probability at pre-synaptic terminals and is involved in vesicular trafficking and/or regulation of the readily releasable pool size. Finally, we found that hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice. These observations suggest that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, but their roles in mature brains were only partially known. Here, we demonstrated, at mature pre-synaptic terminals, that SAD-B regulates vesicular release probability and synaptic plasticity. Moreover, hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice, suggesting that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. PMID:26444684

  12. Modelling hyporheic processes for regulated rivers under transient hydrological and hydrogeological conditions

    NASA Astrophysics Data System (ADS)

    Siergieiev, D.; Ehlert, L.; Reimann, T.; Lundberg, A.; Liedl, R.

    2015-01-01

    Understanding the effects of major hydrogeological controls on hyporheic exchange and bank storage is essential for river water management, groundwater abstraction, restoration and ecosystem sustainability. Analytical models cannot adequately represent complex settings with, for example, transient boundary conditions, varying geometry of surface water-groundwater interface, unsaturated and overland flow, etc. To understand the influence of parameters such as (1) sloping river banks, (2) varying hydraulic conductivity of the riverbed and (3) different river discharge wave scenarios on hyporheic exchange characteristics such as (a) bank storage, (b) return flows and (c) residence time, a 2-D hydrogeological conceptual model and, subsequently, an adequate numerical model were developed. The numerical model was calibrated against observations in the aquifer adjacent to the hydropower-regulated Lule River, northern Sweden, which has predominantly diurnal discharge fluctuations during summer and long-lasting discharge peaks during autumn and winter. Modelling results revealed that bank storage increased with river wave amplitude, wave duration and smaller slope of the river bank, while maximum exchange flux decreased with wave duration. When a homogeneous clogging layer covered the entire river-aquifer interface, hydraulic conductivity positively affected bank storage. The presence of a clogging layer with hydraulic conductivity < 0.001 m d-1 significantly reduced the exchange flows and virtually eliminated bank storage. The bank storage return/fill time ratio was positively related to wave amplitude and the hydraulic conductivity of the interface and negatively to wave duration and bank slope. Discharge oscillations with short duration and small amplitude decreased bank storage and, therefore, the hyporheic exchange, which has implications for solute fluxes, redox conditions and the potential of riverbeds as fish-spawning locations. Based on these results, river

  13. An evaluation of the stress-negative affect model in explaining alcohol use: the role of components of negative affect and coping style.

    PubMed

    Dermody, Sarah Siodmok; Cheong, JeeWon; Manuck, Stephen

    2013-03-01

    The stress-negative affect model for alcohol use was examined. The mediating roles of different components of negative affect were tested in the context of coping style. Data from 1,057 drinking adults (Mage = 44.45) and 352 drinking college students (Mage = 19.07) collected during 2001-2005 and in 2010, respectively, were examined separately. Participants completed self-administered measures of alcohol use, coping strategies, negative life events, and negative affect. A structural equation modeling framework detected stress-related drinking only in the adult sample. Sadness, anger, and guilt were significant mediators and the significant pathways differed based on coping style. The implications and limitations of the study are discussed. PMID:23368670

  14. Schema-Triggered Cognitive and Affective Response to Music: Applying an Information-Processing Model to Rock 'N' Roll.

    ERIC Educational Resources Information Center

    Voelker, David H.; Pettey, Gary R.

    To account for cognitive and affective responses to popular music, a pilot study used an information processing model to show that affect results largely from the activation of affect-laden schemas by the music stimulus. Subjects, 196 students from an introductory course in interpersonal communication at a medium-sized university, listened to a…

  15. Nitric Oxide Affects ERK Signaling through Down-Regulation of MAP Kinase Phosphatase Levels during Larval Development of the Ascidian Ciona intestinalis

    PubMed Central

    Palumbo, Anna

    2014-01-01

    In the ascidian Ciona intestinalis larval development and metamorphosis require a complex interplay of events, including nitric oxide (NO) production, MAP kinases (ERK, JNK) and caspase-3 activation. We have previously shown that NO levels affect the rate of metamorphosis, regulate caspase activity and promote an oxidative stress pathway, resulting in protein nitration. Here, we report that NO down-regulates MAP kinase phosphatases (mkps) expression affecting positively ERK signaling. By pharmacological approach, we observed that the reduction of endogenous NO levels caused a decrease of ERK phosphorylation, whereas increasing levels of NO induced ERK activation. We have also identified the ERK gene network affected by NO, including mpk1, mpk3 and some key developmental genes by quantitative gene expression analysis. We demonstrate that NO induces an ERK-independent down-regulation of mkp1 and mkp3, responsible for maintaining the ERK phosphorylation levels necessary for transcription of key metamorphic genes, such as the hormone receptor rev-erb and the van willebrand protein vwa1c. These results add new insights into the role played by NO during larval development and metamorphosis in Ciona, highlighting the cross-talk between different signaling pathways. PMID:25058405

  16. Mutation in cysteine bridge domain of the gamma-subunit affects light regulation of the ATP synthase in Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The chloroplast ATP synthase functions to synthesize ATP from ADP and free phosphate coupled by the electrochemical potential across the thylakoid membrane in the light. The light-dependent regulation of ATP synthase activity is carried out in part through redox modulation of a cysteine bridge in CF...

  17. Mental Imagery, Impact, and Affect: A Mediation Model for Charitable Giving.

    PubMed

    Dickert, Stephan; Kleber, Janet; Västfjäll, Daniel; Slovic, Paul

    2016-01-01

    One of the puzzling phenomena in philanthropy is that people can show strong compassion for identified individual victims but remain unmoved by catastrophes that affect large numbers of victims. Two prominent findings in research on charitable giving reflect this idiosyncrasy: The (1) identified victim and (2) victim number effects. The first of these suggests that identifying victims increases donations and the second refers to the finding that people's willingness to donate often decreases as the number of victims increases. While these effects have been documented in the literature, their underlying psychological processes need further study. We propose a model in which identified victim and victim number effects operate through different cognitive and affective mechanisms. In two experiments we present empirical evidence for such a model and show that different affective motivations (donor-focused vs. victim-focused feelings) are related to the cognitive processes of impact judgments and mental imagery. Moreover, we argue that different mediation pathways exist for identifiability and victim number effects. PMID:26859848

  18. Modeling the Ferrite-Austenite Transformation in the Heat-Affected Zone of Stainless Steel Welds

    SciTech Connect

    Vitek, J.M.; David, S.A.

    1997-12-01

    The diffusion-controlled ferrite-austenite transformation in stainless steel welds was modeled. An implicit finite-difference analysis that considers multi-component diffusion was used. The model was applied to the Fe-Cr-Ni system to investigate the ferrite- austenite transformation in the heat-affected zone of stainless steel weld metal. The transformation was followed as a function of time as the heat-affected zone was subjected to thermal cycles comparable to those experienced during gas-tungsten arc welding. The results showed that the transformation behavior and the final microstructural state are very sensitive to the maximum temperature that is experienced by the heat-affected zone. For high maximum exposure temperatures ({approximately} 1300{degree} C), the ferrite formation that occurs at the highest temperatures is not completely offset by the reverse ferrite dissolution at lower temperatures. As a result, for high temperature exposures there is a net increase in the amount of ferrite in the microstructure. It was also found that if compositional gradients are present in the initial ferrite and austenite phases, the extent of the transformation is impacted.

  19. Mental Imagery, Impact, and Affect: A Mediation Model for Charitable Giving

    PubMed Central

    Dickert, Stephan; Kleber, Janet; Västfjäll, Daniel; Slovic, Paul

    2016-01-01

    One of the puzzling phenomena in philanthropy is that people can show strong compassion for identified individual victims but remain unmoved by catastrophes that affect large numbers of victims. Two prominent findings in research on charitable giving reflect this idiosyncrasy: The (1) identified victim and (2) victim number effects. The first of these suggests that identifying victims increases donations and the second refers to the finding that people’s willingness to donate often decreases as the number of victims increases. While these effects have been documented in the literature, their underlying psychological processes need further study. We propose a model in which identified victim and victim number effects operate through different cognitive and affective mechanisms. In two experiments we present empirical evidence for such a model and show that different affective motivations (donor-focused vs. victim-focused feelings) are related to the cognitive processes of impact judgments and mental imagery. Moreover, we argue that different mediation pathways exist for identifiability and victim number effects. PMID:26859848

  20. Team Regulation in a Simulated Medical Emergency: An In-Depth Analysis of Cognitive, Metacognitive, and Affective Processes

    ERIC Educational Resources Information Center

    Duffy, Melissa C.; Azevedo, Roger; Sun, Ning-Zi; Griscom, Sophia E.; Stead, Victoria; Crelinsten, Linda; Wiseman, Jeffrey; Maniatis, Thomas; Lachapelle, Kevin

    2015-01-01

    This study examined the nature of cognitive, metacognitive, and affective processes among a medical team experiencing difficulty managing a challenging simulated medical emergency case by conducting in-depth analysis of process data. Medical residents participated in a simulation exercise designed to help trainees to develop medical expertise,…

  1. Volunteer Client Adult Attachment, Memory for In-Session Emotion, and Mood Awareness: An Affect Regulation Perspective

    ERIC Educational Resources Information Center

    Woodhouse, Susan S.; Gelso, Charles J.

    2008-01-01

    In this study, the authors examined relations between volunteer client adult attachment and both (a) memory for negative affect occurring within the first session of therapy and (b) mood awareness (mood labeling and mood monitoring). Participants were 80 volunteer clients (students with a personal issue who volunteered to participate in the…

  2. Using the WTO/TBT enquiry point to monitor tendencies in the regulation of environment, health, and safety issues affecting the chemical industry.

    PubMed

    Pio Borges Menezes, Rodrigo; Maria de Souza Antunes, Adelaide

    2005-04-01

    The growing importance of technical regulation affecting the use and sale of chemical products is a topic of interest not only for the chemical industry, but also for governments, nongovernmental organizations, consumers, and interested communities. The results of such regulation on behalf of the environment, health and safety of individuals, as well as its economic effects on industrial activity, are well understood in the United States and recently in the European Union. In less developed countries, however, the general level of public understanding of these issues is still minimal. It is common knowledge that the so-called "regulatory asymmetry" between countries at different levels of development contributes to the establishment of technical barriers to trade. Such asymmetries, however, also have other impacts: the displacement of polluting industrial sectors to countries which have less demanding regulations, the concentration of unsafe and harmful environmental conditions in certain parts of the globe, and the competitive disadvantage for industries located in countries where control is more rigid. This study analyses information on a wide range of technical regulations issued by World Trade Organization (WTO) members, and focuses on those regulations that affect the chemical industry. This information is available through the WTO Enquiry Points, organizations created in each country to administrate the Technical Barriers to Trade Agreement (TBT). This article consists of an analysis of 4,301 notifications of technical regulations by WTO member states in the 7-year period following the establishment of the WTO in 1995. Starting from this mass of information, 585 notifications that affect the circulation or use of chemical products were isolated. Of this group, 71% refer to only 15 countries. This group of notifications was further classified according to their motivation (the environment, health, safety), by the type of product affected (medications, fuels

  3. The Many Faces of Affect: A Multilevel Model of Drinking Frequency/Quantity and Alcohol Dependence Symptoms Among Young Adults

    PubMed Central

    Simons, Jeffrey S.; Wills, Thomas A.; Neal, Dan J.

    2016-01-01

    This research tested a multilevel structural equation model of associations between 3 aspects of affective functioning (state affect, trait affect, and affective lability) and 3 alcohol outcomes (likelihood of drinking, quantity on drinking days, and dependence symptoms) in a sample of 263 college students. Participants provided 49 days of experience sampling data over 1.3 years in a longitudinal burst design. Within-person results: At the daily level, positive affect was directly associated with greater likelihood and quantity of alcohol consumption. Daily negative affect was directly associated with higher consumption on drinking days and with higher dependence symptoms. Between-person direct effects: Affect lability was associated with higher trait negative, but not positive, affect. Trait positive affect was inversely associated with the proportion of drinking days, whereas negative affectivity predicted a greater proportion of drinking days. Affect lability exhibited a direct association with dependence symptoms. Between-person indirect effects: Trait positive affect was associated with fewer dependence symptoms via proportion of drinking days. Trait negative affect was associated with greater dependence symptoms via proportion of drinking days. The results distinguish relations of positive and negative affect to likelihood versus amount of drinking and state versus trait drinking outcomes, and highlight the importance of affect variability for predicting alcohol dependence symptoms. PMID:24933278

  4. An investigation of factors affecting elementary school students' BMI values based on the system dynamics modeling.

    PubMed

    Lan, Tian-Syung; Chen, Kai-Ling; Chen, Pin-Chang; Ku, Chao-Tai; Chiu, Pei-Hsuan; Wang, Meng-Hsiang

    2014-01-01

    This study used system dynamics method to investigate the factors affecting elementary school students' BMI values. The construction of the dynamic model is divided into the qualitative causal loop and the quantitative system dynamics modeling. According to the system dynamics modeling, this study consisted of research on the four dimensions: student's personal life style, diet-relevant parenting behaviors, advocacy and implementation of school nutrition education, and students' peer interaction. The results of this study showed that students with more adequate health concepts usually have better eating behaviors and consequently have less chance of becoming obese. In addition, this study also verified that educational attainment and socioeconomic status of parents have a positive correlation with students' amounts of physical activity, and nutrition education has a prominent influence on changing students' high-calorie diets. PMID:24701250

  5. Runx1 Regulates Myeloid Precursor Differentiation Into Osteoclasts Without Affecting Differentiation Into Antigen Presenting or Phagocytic Cells in Both Males and Females.

    PubMed

    Paglia, David N; Yang, Xiaochuan; Kalinowski, Judith; Jastrzebski, Sandra; Drissi, Hicham; Lorenzo, Joseph

    2016-08-01

    Runt-related transcription factor 1 (Runx1), a master regulator of hematopoiesis, is expressed in preosteoclasts. Previously we evaluated the bone phenotype of CD11b-Cre Runx1(fl/fl) mice and demonstrated enhanced osteoclasts and decreased bone mass in males. However, an assessment of the effects of Runx1 deletion in female osteoclast precursors was impossible with this model. Moreover, the role of Runx1 in myeloid cell differentiation into other lineages is unknown. Therefore, we generated LysM-Cre Runx1(fl/fl) mice, which delete Runx1 equally (∼80% deletion) in myeloid precursor cells from both sexes and examined the capacity of these cells to differentiate into osteoclasts and phagocytic and antigen-presenting cells. Both female and male LysM-Cre Runx1(fl/fl) mice had decreased trabecular bone mass (72% decrease in bone volume fraction) and increased osteoclast number (2-3 times) (P < .05) without alteration of osteoblast histomorphometric indices. We also demonstrated that loss of Runx1 in pluripotential myeloid precursors with LysM-Cre did not alter the number of myeloid precursor cells in bone marrow or their ability to differentiate into phagocytizing or antigen-presenting cells. This study demonstrates that abrogation of Runx1 in multipotential myeloid precursor cells significantly and specifically enhanced the ability of receptor activator of nuclear factor-κB ligand to stimulate osteoclast formation and fusion in female and male mice without affecting other myeloid cell fates. In turn, increased osteoclast activity in LysM-Cre Runx1(fl/fl) mice likely contributed to a decrease in bone mass. These dramatic effects were not due to increased osteoclast precursors in the deleted mutants and argue that inhibition of Runx1 in multipotential myeloid precursor cells is important for osteoclast formation and function. PMID:27267711

  6. Cellular Intrinsic Mechanism Affecting the Outcome of AML Treated with Ara-C in a Syngeneic Mouse Model

    PubMed Central

    Tan, Dongming; Su, Guangsong; Zheng, Yanwen; He, Chao; Mao, Zhengwei J.; Singleton, Timothy P.; Yin, Bin

    2014-01-01

    The mechanisms underlying acute myeloid leukemia (AML) treatment failure are not clear. Here, we established a mouse model of AML by syngeneic transplantation of BXH-2 derived myeloid leukemic cells and developed an efficacious Ara-C-based regimen for treatment of these mice. We proved that leukemic cell load was correlated with survival. We also demonstrated that the susceptibility of leukemia cells to Ara-C could significantly affect the survival. To examine the molecular alterations in cells with different sensitivity, genome-wide expression of the leukemic cells was profiled, revealing that overall 366 and 212 genes became upregulated or downregulated, respectively, in the resistant cells. Many of these genes are involved in the regulation of cell cycle, cellular proliferation, and apoptosis. Some of them were further validated by quantitative PCR. Interestingly, the Ara-C resistant cells retained the sensitivity to ABT-737, an inhibitor of anti-apoptosis proteins, and treatment with ABT-737 prolonged the life span of mice engrafted with resistant cells. These results suggest that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C. Incorporation of apoptosis inhibitors, such as ABT-737, into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. This work provided direct in vivo evidence that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C, suggesting that incorporation of apoptosis inhibitors into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. PMID:25314317

  7. 75 FR 41084 - Amendments to Regulations Regarding Major Life-Changing Events Affecting Income-Related Monthly...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-15

    ...We are modifying our regulations to clarify and revise what we consider major life-changing events for the Medicare Part B income- related monthly adjustment amount (IRMAA) and what evidence we require to support a claim of a major life-changing event. Recent changes in the economy and other unforeseen events have had a significant effect on many Medicare Part B beneficiaries. The changes we......

  8. Overview of Development and Deployment of Codes, Standards and Regulations Affecting Energy Storage System Safety in the United States

    SciTech Connect

    Conover, David R.

    2014-08-22

    This report acquaints stakeholders and interested parties involved in the development and/or deployment of energy storage systems (ESS) with the subject of safety-related codes, standards and regulations (CSRs). It is hoped that users of this document gain a more in depth and uniform understanding of safety-related CSR development and deployment that can foster improved communications among all ESS stakeholders and the collaboration needed to realize more timely acceptance and approval of safe ESS technology through appropriate CSR.

  9. DNA topology affects transcriptional regulation of the pertussis toxin gene of Bordetella pertussis in Escherichia coli and in vitro.

    PubMed Central

    Scarlato, V; Aricò, B; Rappuoli, R

    1993-01-01

    The bvg locus of Bordetella pertussis encodes an environmentally inducible operon essential for the expression of virulence genes. We show that in Escherichia coli, the PTOX promoter cloned in cis of the bvg locus is activated and environmentally regulated. Cotransformation of E. coli with the bvg locus cloned in a low-copy-number plasmid and with the PTOX promoter cloned in a high-copy-number plasmid can give rise to two different results. If the PTOX promoter is cloned in the pGem-3 vector, transcription is absent. If the PTOX promoter is cloned in the plasmid pKK232, containing the PTOX promoter between two ribosomal gene terminators of transcription, transcription occurs, although regulation of transcription is abolished. Under these conditions, the intracellular amount of RNA transcripts is increased by adding to the culture medium novobiocin, an inhibitor of bacterial gyrases. In vitro, the transcription of the PTOX promoter is activated on E. coli RNA polymerase supplemented with cell extracts from wild-type B. pertussis. Addition of DNA gyrase to the mixture dramatically reduces the amount of RNA synthesized. Our data show that the products of the bvg locus, BvgA and BvgS, are directly involved in the regulation of the PTOX promoter in E. coli and that DNA topology may play a role in the induction of transcription. Images PMID:8393006

  10. VLN2 Regulates Plant Architecture by Affecting Microfilament Dynamics and Polar Auxin Transport in Rice[OPEN

    PubMed Central

    Wu, Shengyang; Xie, Yurong; Guo, Xiuping; Sheng, Peike; Wang, Juan; Wu, Chuanyin; Wang, Haiyang; Wan, Jianmin

    2015-01-01

    As a fundamental and dynamic cytoskeleton network, microfilaments (MFs) are regulated by diverse actin binding proteins (ABPs). Villins are one type of ABPs belonging to the villin/gelsolin superfamily, and their function is poorly understood in monocotyledonous plants. Here, we report the isolation and characterization of a rice (Oryza sativa) mutant defective in VILLIN2 (VLN2), which exhibits malformed organs, including twisted roots and shoots at the seedling stage. Cellular examination revealed that the twisted phenotype of the vln2 mutant is mainly caused by asymmetrical expansion of cells on the opposite sides of an organ. VLN2 is preferentially expressed in growing tissues, consistent with a role in regulating cell expansion in developing organs. Biochemically, VLN2 exhibits conserved actin filament bundling, severing and capping activities in vitro, with bundling and stabilizing activity being confirmed in vivo. In line with these findings, the vln2 mutant plants exhibit a more dynamic actin cytoskeleton network than the wild type. We show that vln2 mutant plants exhibit a hypersensitive gravitropic response, faster recycling of PIN2 (an auxin efflux carrier), and altered auxin distribution. Together, our results demonstrate that VLN2 plays an important role in regulating plant architecture by modulating MF dynamics, recycling of PIN2, and polar auxin transport. PMID:26486445

  11. MicroRNA-155 may affect allograft survival by regulating the expression of suppressor of cytokine signaling 1.

    PubMed

    Zhang, Maomao; Zhang, Qi; Liu, Fang; Yin, Li; Yu, Bo; Wu, Jian

    2011-10-01

    Immune rejection of organ transplants has life-threatening implications. It is believed that allograft rejection is initiated by the activation of lymphocytes following recognition of donor antigens, leading to generation of effector T lymphocytes, alloantibody production, and graft infiltration by alloreactive cells. There is solid evidence that miRNAs are integral for maintaining immune homeostasis and self-tolerance. A deeper understanding of the regulation of the immune response by miRNAs could define new mechanisms for manipulating graft immunity and preventing rejection. The miRNA miR-155 is of particular interest due to its known roles in regulating the expression of genes relevant to allograft rejection and the induction of immune tolerance. Indeed, miR-155 has been shown to dramatically impact both innate and adaptive immune processes, including inflammation, antigen presentation, T-cell differentiation, cytokine production, and T regulatory cell (Treg) functions. The suppressor of cytokine signaling 1 (SOCS1) is a critical regulator of immune cell function and an evolutionarily conserved target of miR-155 in breast cancer cells. We propose that suppression of miR-155 could enhance SOCS1 expression in immune cells and suppress allograft rejection. Further studies on the specific role of miR-155 in allograft rejection may lead to the identification of new targets for therapeutic intervention. PMID:21802214

  12. Modeling physicochemical interactions affecting in vitro cellular dosimetry of engineered nanomaterials: application to nanosilver

    PubMed Central

    Mukherjee, Dwaipayan; Leo, Bey Fen; Royce, Steven G.; Porter, Alexandra E.; Ryan, Mary P.; Schwander, Stephan; Chung, Kian Fan; Tetley, Teresa D.; Zhang, Junfeng; Georgopoulos, Panos G.

    2014-01-01

    Engineered nanomaterials (ENMs) possess unique characteristics affecting their interactions in biological media and biological tissues. Systematic investigation of the effects of particle properties on biological toxicity requires a comprehensive modeling framework which can be used to predict ENM particokinetics in a variety of media. The Agglomeration-diffusion-sedimentation-reaction model (ADSRM) described here is stochastic, using a direct simulation Monte Carlo method to study the evolution of nanoparticles in biological media, as they interact with each other and with the media over time. Nanoparticle diffusion, gravitational settling, agglomeration, and dissolution are treated in a mechanistic manner with focus on silver ENMs (AgNPs). The ADSRM model utilizes particle properties such as size, density, zeta potential, and coating material, along with medium properties like density, viscosity, ionic strength, and pH, to model evolving patterns in a population of ENMs along with their interaction with associated ions and molecules. The model predictions for agglomeration and dissolution are compared with in vitro measurements for various types of ENMs, coating materials, and incubation media, and are found to be overall consistent with measurements. The model has been implemented for an in vitro case in cell culture systems to inform in vitro dosimetry for toxicology studies, and can be directly extended to other biological systems, including in vivo tissue subsystems by suitably modifying system geometry. PMID:25598696

  13. Statistical model selection for better prediction and discovering science mechanisms that affect reliability

    DOE PAGESBeta

    Anderson-Cook, Christine M.; Morzinski, Jerome; Blecker, Kenneth D.

    2015-08-19

    Understanding the impact of production, environmental exposure and age characteristics on the reliability of a population is frequently based on underlying science and empirical assessment. When there is incomplete science to prescribe which inputs should be included in a model of reliability to predict future trends, statistical model/variable selection techniques can be leveraged on a stockpile or population of units to improve reliability predictions as well as suggest new mechanisms affecting reliability to explore. We describe a five-step process for exploring relationships between available summaries of age, usage and environmental exposure and reliability. The process involves first identifying potential candidatemore » inputs, then second organizing data for the analysis. Third, a variety of models with different combinations of the inputs are estimated, and fourth, flexible metrics are used to compare them. As a result, plots of the predicted relationships are examined to distill leading model contenders into a prioritized list for subject matter experts to understand and compare. The complexity of the model, quality of prediction and cost of future data collection are all factors to be considered by the subject matter experts when selecting a final model.« less

  14. Statistical model selection for better prediction and discovering science mechanisms that affect reliability

    SciTech Connect

    Anderson-Cook, Christine M.; Morzinski, Jerome; Blecker, Kenneth D.

    2015-08-19

    Understanding the impact of production, environmental exposure and age characteristics on the reliability of a population is frequently based on underlying science and empirical assessment. When there is incomplete science to prescribe which inputs should be included in a model of reliability to predict future trends, statistical model/variable selection techniques can be leveraged on a stockpile or population of units to improve reliability predictions as well as suggest new mechanisms affecting reliability to explore. We describe a five-step process for exploring relationships between available summaries of age, usage and environmental exposure and reliability. The process involves first identifying potential candidate inputs, then second organizing data for the analysis. Third, a variety of models with different combinations of the inputs are estimated, and fourth, flexible metrics are used to compare them. As a result, plots of the predicted relationships are examined to distill leading model contenders into a prioritized list for subject matter experts to understand and compare. The complexity of the model, quality of prediction and cost of future data collection are all factors to be considered by the subject matter experts when selecting a final model.

  15. Regulation of the proliferation of colon cancer cells by compounds that affect glycolysis, including 3-bromopyruvate, 2-deoxyglucose and biguanides.

    PubMed

    Lea, Michael A; Qureshi, Mehreen S; Buxhoeveden, Michael; Gengel, Nicolette; Kleinschmit, Jessica; Desbordes, Charles

    2013-02-01

    In previous studies performed by our group, we observed that 2-deoxyglucose blocked the acidification of the medium used for culture of colon cancer cells caused by incubation with biguanides and it had an additive inhibitory effect on growth. In the present work, we found that 3-bromopyruvate can also prevent the lowering of pH caused by biguanide treatment. 3-Bromopyruvate inhibited colonic cancer cell proliferation, but the effect was not always additive to that of biguanides and an additive effect was more notable in combined treatment with 3-bromopyruvate and 2-deoxyglucose. The induction of alkaline phosphatase activity by butyrate was not consistently affected by combination with other agents that modified glucose metabolism. The drug combinations that were examined inhibited proliferation of wild-type and p53-null cells and affected colonic cancer lines with different growth rates. PMID:23393330

  16. Analysis of factors affecting satisfaction level on problem based learning approach using structural equation modeling

    NASA Astrophysics Data System (ADS)

    Hussain, Nur Farahin Mee; Zahid, Zalina

    2014-12-01

    Nowadays, in the job market demand, graduates are expected not only to have higher performance in academic but they must also be excellent in soft skill. Problem-Based Learning (PBL) has a number of distinct advantages as a learning method as it can deliver graduates that will be highly prized by industry. This study attempts to determine the satisfaction level of engineering students on the PBL Approach and to evaluate their determinant factors. The Structural Equation Modeling (SEM) was used to investigate how the factors of Good Teaching Scale, Clear Goals, Student Assessment and Levels of Workload affected the student satisfaction towards PBL approach.

  17. High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model

    PubMed Central

    Larmonier, C. B.; McFadden, R.-M. T.; Hill, F. M.; Schreiner, R.; Ramalingam, R.; Besselsen, D. G.; Ghishan, F. K.

    2013-01-01

    Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D3 has been considered a viable adjunctive therapy in IBD. However, vitamin D3 plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D3 supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10−/− CD4+ T cell transfer model of chronic colitis. High-dose vitamin D3 supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D3 metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D3 supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D3 diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D3 group. Our data suggest that vitamin D3, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D3 supplementation in patients with active IBD. PMID:23639807

  18. When to throw the switch: The adaptiveness of modifying emotion regulation strategies based on affective and physiological feedback.

    PubMed

    Birk, Jeffrey L; Bonanno, George A

    2016-08-01

    Particular emotion regulation (ER) strategies are beneficial in certain contexts, but little is known about the adaptiveness of switching strategies after implementing an initial strategy. Research and theory on regulatory flexibility suggest that people switch strategies dynamically and that internal states provide feedback indicating when switches are appropriate. Frequent switching may predict positive outcomes among people who respond to this feedback. We investigated whether internal feedback (particularly corrugator activity, heart rate, or subjective negative intensity) guides people to switch to an optimal (i.e., distraction) but not nonoptimal (i.e., reappraisal) strategy for regulating strong emotion. We also tested whether switching frequency and responsiveness to internal feedback (RIF) together predict well-being. While attempting to regulate emotion elicited by unpleasant pictures, participants could switch to an optimal (Study 1; reappraisal-to-distraction order; N = 90) or nonoptimal (Study 2; distraction-to-reappraisal order; N = 95) strategy for high-arousal emotion. A RIF score for each emotion measure indexed the relative strength of emotion during the initial phase for trials on which participants later switched strategies. As hypothesized, negative intensity, corrugator activity, and the magnitude of heart rate deceleration during this early phase were higher on switch than maintain trials in Study 1 only. Critically, in Study 1 only, greater switching frequency predicted higher and lower life satisfaction for participants with high and low corrugator RIF, respectively, even after controlling for reappraisal success. Individual differences in RIF may contribute to subjective well-being provided that the direction of strategy switching aligns well with regulatory preferences for high emotion. (PsycINFO Database Record PMID:26900993

  19. STAT3 regulated ATR via microRNA-383 to control DNA damage to affect apoptosis in A431 cells.

    PubMed

    Liao, Xing-Hua; Zheng, Li; He, Hong-Peng; Zheng, De-Liang; Wei, Zhao-Qiang; Wang, Nan; Dong, Jian; Ma, Wen-Jian; Zhang, Tong-Cun

    2015-11-01

    Skin cancer is a major cause of morbidity and mortality worldwide. Mounting evidence shows that exposure of the skin to solar UV radiation results in inflammation, oxidative stress, DNA damage, dysregulation of cellular signaling pathways and immunosuppression thereby resulting in skin cancer. Signal transducer and activator of transcription 3 (STAT3) is well known to function as an anti-apoptotic factor, especially in numerous malignancies, but the relationship between STAT3 activation and DNA damage response in skin cancer is still not fully understood. We now report that STAT3 inhibited DNA damage induced by UV and STAT3 mediated upregulation of GADD45γ and MDC-1 and the phosphorylation of H2AX in UV induced DNA damage. Notably, STAT3 can increase the expression of ATR in A431 cells. Luciferase assay shows that STAT3 activates the transcription of ATR promoter. More importantly, microRNA-383 suppressed ATR expression by targeting 3' (untranslated regions)UTR of ATR in A431 cells, and STAT3 down-regulates the transcription of miR-383 promoter. Thus, these results reveal the new insight that ATR is down-regulated by STAT3-regulated microRNA-383 in A431 cells. Moreover, overexpression of STAT3 enhanced expression of antiapoptosis genes BCL-1 and MCL-1, and depletion of STAT3 sensitized A431 cells to apoptotic cell death following UV. Collectively, these studies suggest that STAT3 may be a potential target for both the prevention and treatment of human skin cancer. PMID:26261078

  20. Pyrabactin regulates root hydraulic properties in maize seedlings by affecting PIP aquaporins in a phosphorylation-dependent manner.

    PubMed

    Fan, Wenqiang; Li, Jia; Jia, Jia; Wang, Fei; Cao, Cuiling; Hu, Jingjiang; Mu, Zixin

    2015-09-01

    Pyrabactin, an agonist of abscisic acid (ABA), has led to the isolation and characterization of pyrabactin resistance 1/pyrabactin resistance 1-like (PYR1/PYLs) ABA receptors in Arabidopsis, which has well explained ABA-mediated stomatal movement and stress-related gene expression. In addition to inducing stomatal closure and inhibiting transpiration, ABA can also enhance root hydraulic conductivity (Lpr), thus maintaining water balance under water deficiency-related stress, but its molecular mechanism remains unclear. In the present study, the root hydraulic properties of maize seedlings in response to pyrabactin were compared to those caused by ABA. Similar to ABA, lower concentration of pyrabactin induced a remarkable increase in Lpr as well as in the gene expression of the plasma membrane intrinsic protein (ZmPIP) aquaporin and in the ZmPIP2; 1/2; 2 protein abundance. The pyrabactin-induced enhancement of Lpr was abolished by H2O2 application, indicating that pyrabactin regulates Lpr by modulating ZmPIP at transcriptional, translational and post-translational (activity) level. Pyrabactin-mediated water transport and ZmPIP gene expression were phosphorylation-dependent, suggesting that ABA-PYR1-(PP2C)-protein kinase-AQP signaling pathway may be involved in this process. As we know this is the first established ABA signaling transduction pathway that mediated water transport in roots. This observation further addressed the importance of PYR1/PYLs ABA receptor in regulating plant water use efficiency from the under ground level. Except inhibiting transpiration in leaves, our result introduces the exciting possibility of application ABA agonists for regulating roots water uptake in field, with a species- and dose dependent manner. PMID:26000467

  1. Phase and frequency locking in the model of cardiovascular system baroreflectory regulation

    NASA Astrophysics Data System (ADS)

    Ishbulatov, Yurii M.; Karavaev, Anatoly S.; Kiselev, Anton R.; Ponomarenko, Vladimir I.; Prokhorov, Mikhail D.

    2016-04-01

    We proposed the model of cardiovascular system which describes the sinus rhythm, autonomic regulation of heart and arterial vessels, baroreflex, arterial pressure and respiration process. The model included a self-oscillating loop of regulation of mean arterial pressure. It was shown that suggested model more accurately simulated the spectral and statistical characteristics of heart rate variability signal in comparison with the model proposed earlier by Seidel and Herzel.

  2. Economic impact of proposed site-specific changes to water-pollution regulation affecting Joliet, Illinois. Final report

    SciTech Connect

    Pershall, R.B.

    1988-05-01

    This report provides an analysis of the economic and environmental impacts of a petition filed by the City of Joliet requesting site-specific relief from Illinois state water-quality regulations for biological oxygen demands (BOD) and suspended solids. Joliet proposes that its Eastside Wastewater Treatment plant be allowed to meet effluent limitations established for the Des Plains River rather than the effluent limitations for Hickory Creek. The study examines two general strategies for complying with the existing standards. One possibility is to upgrade the current treatment system. The other option analyzes relocating the outfall to the Des Plaines River.

  3. The kinesin-13 KLP10A motor regulates oocyte spindle length and affects EB1 binding without altering microtubule growth rates.

    PubMed

    Do, Kevin K; Hoàng, Kim Liên; Endow, Sharyn A

    2014-01-01

    Kinesin-13 motors are unusual in that they do not walk along microtubules, but instead diffuse to the ends, where they remove tubulin dimers, regulating microtubule dynamics. Here we show that Drosophila kinesin-13 klp10A regulates oocyte meiosis I spindle length and is haplo-insufficient - KLP10A, reduced by RNAi or a loss-of-function P element insertion mutant, results in elongated and mispositioned oocyte spindles, and abnormal cortical microtubule asters and aggregates. KLP10A knockdown by RNAi does not significantly affect microtubule growth rates in oocyte spindles, but, unexpectedly, EB1 binding and unbinding are slowed, suggesting a previously unobserved role for kinesin-13 in mediating EB1 binding interactions with microtubules. Kinesin-13 may regulate spindle length both by disassembling subunits from microtubule ends and facilitating EB1 binding to plus ends. We also observe an increased number of paused microtubules in klp10A RNAi knockdown spindles, consistent with a reduced frequency of microtubule catastrophes. Overall, our findings indicate that reduced kinesin-13 decreases microtubule disassembly rates and affects EB1 interactions with microtubules, rather than altering microtubule growth rates, causing spindles to elongate and abnormal cortical microtubule asters and aggregates to form. PMID:24907370

  4. Do regulated resident working hours affect medical graduate education? Trends in the American psychiatry board pass rates pre- and post-2003 duty hours regulations.

    PubMed

    Jain, Gaurav; Dzara, Kristina; Mazhar, Mir Nadeem; Punwani, Manisha

    2014-12-01

    Aims and method To assess trends of the American Board of Psychiatry and Neurology examination pass rates before and after the 2003 duty hours regulations (DHR). We obtained the pass rates for part I and II for years 2000-2010. Data were divided pre-DHR (2000-2003) and post-DHR (2007-2010). Results During the pre-DHR period, first- and multiple-attempt group pass rates were 80.7% and 39.0% which changed in the post-DHR period to 89.7% and 39.1% respectively. Similarly for the part II exam, the pre-DHR first- and multiple-attempt group pass rates were 60.2% and 43.5% respectively, which increased to 78.7% and 53.8%, among the post-DHR group. Overall, there was a significant increase in the first-attempt candidates pass rates for parts I and II, whereas multiple-attempt candidates did not benefit as strongly. Clinical implications The results suggest that the 2003 DHR may have had a positive impact on examination-based medical knowledge in psychiatry. PMID:25505632

  5. Outcome assessment of a computer-animated model for learning about the regulation of glomerular filtration rate.

    PubMed

    Gookin, Jody L; McWhorter, Dan; Vaden, Shelly; Posner, Lysa

    2010-06-01

    The regulation of the glomerular filtration rate (GFR) is a particularly important and challenging concept for students to integrate into a memorable framework for building further knowledge and solving clinical problems. In this study, 76 first-year veterinary students and 19 veterinarians in clinical specialty training (house officers) participated in separate online exercises to evaluate the use of a computer-animated model of GFR regulation (www.aamc.org/mededportal) on learning outcome. Students were randomly allocated to study either the animated model or written materials before completion of a 10-question multiple-choice quiz. House officers completed a 35-question test before and after study of the animated model. Both groups completed a survey about the learning exercise. The ability of the model to enhance learning was demonstrated by a significant improvement (P < 0.001) in the test performance of house officers after studying the model. The model performed similarly to written materials alone in affecting the subsequent quiz performance of the students. The majority of students and house officers agreed or strongly agreed that the animated model was easy to understand, improved their knowledge and appreciation of the importance of GFR regulation, and that they would recommend the model to peers. Most students [63 of 76 students (83%)] responded that they would prefer the use of the animated model alone over the study of written materials but acknowledged that a combination of hardcopy written notes and the animated model would be ideal. A greater applicability of the model to more advanced students and an introduction in a didactic setting before individual study were suggested by the house officers. The results of this study suggest that the animated model is a useful, effective, and well-received tool for learning and creating a visual memory of the regulatory mechanisms of GFR. PMID:20522905

  6. Stanniocalcin-1 Protects a Mouse Model from Renal Ischemia-Reperfusion Injury by Affecting ROS-Mediated Multiple Signaling Pathways

    PubMed Central

    Liu, Dajun; Shang, Huiping; Liu, Ying

    2016-01-01

    Stanniocalcin-1 (STC-1) protects against renal ischemia-reperfusion injury (RIRI). However, the molecular mechanisms remain widely unknown. STC-1 inhibits reactive oxygen species (ROS), whereas most ROS-mediated pathways are associated with ischemic injury. Therefore, to explore the mechanism, the effects of STC-1 on ROS-medicated pathways were studied. Non-traumatic vascular clamps were used to establish RIRI mouse models. The serum levels of STC-1, interleukin-6 (IL-6), interferon (IFN) γ, P53, and capase-3 were measured by ELISA kits. Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by fluorescence spectrofluorometer. All these molecules changed significantly in a RIRI model mouse when compared with those in a sham control. Kidney cells were isolated from sham and model mice. STC-1 was overexpressed or knockout in these kidney cells. The molecules in ROS-medicated pathways were measured by real-time quantitative PCR and Western blot. The results showed that STC-1 is an effective ROS scavenger. The serum levels of STC-1, MDA and SOD activity were increased while the serum levels of IL-6, iIFN-γ, P53, and capase-3 were decreased in a model group when compared with a sham control (p < 0.05). Furthermore, the levels of STC-1,p53, phosphorylated mitogen-activated protein kinase kinase (p-MEKK-1), c-Jun N-terminal kinase (p-JNK), extracellular signal-regulated kinase (p-ERK), IkB kinase (p-IKK), nuclear factor (NF) κB, apoptosis signal-regulating kinase 1 (ASK-1) and caspase-3 changed significantly in kidney cells isolated from a RIRI model when compared to those isolated from a sham control (p < 0.05). Meanwhile, STC-1 overexpression or silence caused significant changes of the levels of these ROS-mediated molecules. Therefore, STC-1 maybe improve anti-inflammation, anti-oxidant and anti-apoptosis activities by affecting ROS-mediated pathways, especially the phospho-modifications of the respective proteins, resulting in the increase of SOD and

  7. Understanding coupled factors that affect the modelling accuracy of typical planar compliant mechanisms

    NASA Astrophysics Data System (ADS)

    Hao, Guangbo; Li, Haiyang; Kemalcan, Suzen; Chen, Guimin; Yu, Jingjun

    2016-05-01

    In order to accurately model compliant mechanism utilizing plate flexures, qualitative planar stress (Young's modulus) and planar strain (plate modulus) assumptions are not feasible. This paper investigates a quantitative equivalent modulus using nonlinear finite element analysis (FEA) to reflect coupled factors in affecting the modelling accuracy of two typical distributed- compliance mechanisms. It has been shown that all parameters have influences on the equivalent modulus with different degrees; that the presence of large load-stiffening effect makes the equivalent modulus significantly deviate from the planar assumptions in two ideal scenarios; and that a plate modulus assumption is more reasonable for a very large out-of-plane thickness if the beam length is large.

  8. Understanding coupled factors that affect the modelling accuracy of typical planar compliant mechanisms

    NASA Astrophysics Data System (ADS)

    Hao, Guangbo; Li, Haiyang; Kemalcan, Suzen; Chen, Guimin; Yu, Jingjun

    2016-06-01

    In order to accurately model compliant mechanism utilizing plate flexures, qualitative planar stress (Young's modulus) and planar strain (plate modulus) assumptions are not feasible. This paper investigates a quantitative equivalent modulus using nonlinear finite element analysis (FEA) to reflect coupled factors in affecting the modelling accuracy of two typical distributed- compliance mechanisms. It has been shown that all parameters have influences on the equivalent modulus with different degrees; that the presence of large load-stiffening effect makes the equivalent modulus significantly deviate from the planar assumptions in two ideal scenarios; and that a plate modulus assumption is more reasonable for a very large out-of-plane thickness if the beam length is large.

  9. Interplay of model ingredients affecting aggregate shape plasticity in diffusion-limited aggregation.

    PubMed

    Duarte-Neto, P; Stošić, T; Stošić, B; Lessa, R; Milošević, M V

    2014-07-01

    We analyze the combined effect of three ingredients of an aggregation model--surface tension, particle flow and particle source--representing typical characteristics of many aggregation growth processes in nature. Through extensive numerical experiments and for different underlying lattice structures we demonstrate that the location of incoming particles and their preferential direction of flow can significantly affect the resulting general shape of the aggregate, while the surface tension controls the surface roughness. Combining all three ingredients increases the aggregate shape plasticity, yielding a wider spectrum of shapes as compared to earlier works that analyzed these ingredients separately. Our results indicate that the considered combination of effects is fundamental for modeling the polymorphic growth of a wide variety of structures in confined geometries and/or in the presence of external fields, such as rocks, crystals, corals, and biominerals. PMID:25122308

  10. Regulation of PMP22 mRNA by G3BP1 affects cell proliferation in breast cancer cells

    PubMed Central

    2013-01-01

    Background Regulation of mRNAs is one way to control protein levels and thereby important cellular processes such as growth, invasion and apoptosis. G3BPs constitute a family of mRNA-binding proteins, shown to be overexpressed in several cancer types, including breast, colon and pancreas cancer. G3BP has been reported to both stabilize and induce degradation of specific mRNAs. Results Here, we show that G3BP1, but not G3BP2, supports proliferation of several breast cancer cell lines. Global gene expression analyses of G3BP1- and G3BP2-depleted cells indicate that primarily G3BP1, and much less G3BP2, influences mRNA expression levels. Peripheral myelin protein 22 (PMP22) was one gene that was significantly influenced by G3BP1 depletion which led to a 2–3 fold increased expression. Depletion of PMP22 resulted in increased proliferation and the G3BP1-mediated effect on proliferation was not seen upon PMP22-depletion. Conclusions This indicates a novel role for G3BP1 in the regulation of cell proliferation in breast cancer cells, perhaps via a regulatory effect on PMP22 expression. PMID:24321297

  11. Biochemical analysis of the recombinant Fur (ferric uptake regulator) protein from Anabaena PCC 7119: factors affecting its oligomerization state.

    PubMed Central

    Hernández, José A; Bes, M Teresa; Fillat, María F; Neira, José L; Peleato, M Luisa

    2002-01-01

    Fur (ferric uptake regulator) protein is a DNA-binding protein which regulates iron-responsive genes. Recombinant Fur from the nitrogen-fixing cyanobacterium Anabaena PCC 7119 has been purified and characterized, and polyclonal antibodies obtained. The experimental data show that Fur from Anabaena dimerizes in solution with the involvement of disulphide bridges. Cross-linking experiments and MALDI-TOF (matrix-assisted laser desorption/ionization time of flight) MS also show several oligomerization states of Fur, and the equilibrium of these forms depends on protein concentration and ionic strength. In intact recombinant Fur, four cysteine residues out of five were inert towards DTNB [5,5'-dithiobis-(2-nitrobenzoic acid)], and their modification required sodium borohydride. Metal analysis and electrospray ionization MS revealed that neither zinc nor other metals are present in this Fur protein. Purified recombinant Fur bound to its own promoter in gel-shift assays. Fur was shown to be a constitutive protein in Anabaena cells, with no significant difference in its expression in cells grown under iron-sufficient compared with iron-deficient conditions. PMID:12015814

  12. The role of ovarian hormone-derived neurosteroids on the regulation of GABAA receptors in affective disorders

    PubMed Central

    MacKenzie, Georgina; Maguire, Jamie

    2014-01-01

    Rationale Neuroactive derivatives of steroid hormones, neurosteroids, can act on GABAA receptors (GABAARs) to potentiate the effects of GABA on these receptors. Neurosteroids become elevated to physiologically relevant levels under conditions characterized by increased steroid hormones. There is considerable evidence for plasticity of GABAARs associated with altered levels of neurosteroids which may counteract the fluctuations in the levels of these allosteric modulators. Objectives The objective of this review is to summarize the current literature on GABAAR plasticity under conditions characterized by alterations in neurosteroid levels, such as over the estrous cycle, during puberty, and throughout pregnancy and the postpartum period. Results The expression of specific GABAAR subunits are altered over the estrous cycle, at puberty, and throughout pregnancy and the postpartum period. Inability to regulate δ subunit-containing GABAARs throughout pregnancy and the postpartum period is associated with depression-like behavior restricted to the postpartum period. Conclusions GABAAR plasticity associated with alterations in neurosteroid levels represents a homeostatic compensatory mechanism to maintain an ideal level of inhibition to offset the potentiating effects of neurosteroids on GABAergic inhibition. Failure to properly regulate GABAARs under conditions of altered neurosteroid levels may increase vulnerability to mood disorders, such as premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), and postpartum depression. PMID:24402140

  13. The Cystic Fibrosis-causing Mutation ΔF508 Affects Multiple Steps in Cystic Fibrosis Transmembrane Conductance Regulator Biogenesis*

    PubMed Central

    Thibodeau, Patrick H.; Richardson, John M.; Wang, Wei; Millen, Linda; Watson, Jarod; Mendoza, Juan L.; Du, Kai; Fischman, Sharon; Senderowitz, Hanoch; Lukacs, Gergely L.; Kirk, Kevin; Thomas, Philip J.

    2010-01-01

    The deletion of phenylalanine 508 in the first nucleotide binding domain of the cystic fibrosis transmembrane conductance regulator is directly associated with >90% of cystic fibrosis cases. This mutant protein fails to traffic out of the endoplasmic reticulum and is subsequently degraded by the proteasome. The effects of this mutation may be partially reversed by the application of exogenous osmolytes, expression at low temperature, and the introduction of second site suppressor mutations. However, the specific steps of folding and assembly of full-length cystic fibrosis transmembrane conductance regulator (CFTR) directly altered by the disease-causing mutation are unclear. To elucidate the effects of the ΔF508 mutation, on various steps in CFTR folding, a series of misfolding and suppressor mutations in the nucleotide binding and transmembrane domains were evaluated for effects on the folding and maturation of the protein. The results indicate that the isolated NBD1 responds to both the ΔF508 mutation and intradomain suppressors of this mutation. In addition, identification of a novel second site suppressor of the defect within the second transmembrane domain suggests that ΔF508 also effects interdomain interactions critical for later steps in the biosynthesis of CFTR. PMID:20667826

  14. Phosphorylation of Ser-180 of rat aquaporin-4 shows marginal affect on regulation of water permeability: molecular dynamics study.

    PubMed

    Sachdeva, Ruchi; Singh, Balvinder

    2014-04-01

    Water permeation through rat aquaporin-4 (rAQP4), predominantly found in mammalian brain is regulated by phosphorylation of Ser-180. The present study has been carried out to understand the structural mechanism of regulation of water permeability across the channel. Molecular dynamics (MD) simulations have been carried out to investigate the structural changes caused due to phosphorylation of Ser-180 in the tetrameric assembly of rAQP4 along with predicted C-terminal region (255-323). The interactions involving opposite charges are observed between cytoplasmic loops and the C-terminal region during MD simulations. This results in movement of C-terminal region of rAQP4 towards the cytoplasmic mouth of water channel. Despite this movement, there was a gap between C-terminal region and cytoplasmic mouth of the channel through which water molecules were able to gain entry into the channel. The interactions between C-terminus and loop D of neighboring monomers in a tetrameric assembly appear to prevent the complete closure of cytoplasmic mouth of the water channel. Further, the rates of water permeation through phosphorylated and unphosphorylated rAQP4 have also been compared. The simulation studies showed a continuous movement of water in a single file across pore of unphosphorylated as well as phosphorylated rAQP4. PMID:23651078

  15. Post-translational regulation and nuclear entry of TIMELESS and PERIOD are affected in new timeless mutant

    PubMed Central

    Hara, Taichi; Koh, Kyunghee; Combs, David J.; Sehgal, Amita

    2011-01-01

    The molecular circadian clock consists of a feedback loop in which canonical clock proteins negatively regulate transcription of their own genes. Timed nuclear entry of these proteins is critical, but regulation of this event is poorly understood. In Drosophila melanogaster, the idea that nuclear entry of PERIOD (PER) is controlled by its partner protein, TIMELESS (TIM), has been challenged by several studies. We identify here a novel mutation in the tim gene that eliminates behavioral rhythms while allowing robust expression of TIM and PER. Mutant TIM can bind to and stabilize PER. However, neither protein is expressed cyclically, and phosphorylation of both is reduced. In addition, TIM and PER are localized in the cytoplasm at all times of day and mutant TIM attenuates transcriptional feedback by PER in cultured cells, suggesting that it holds PER in the cytoplasm. In fact, much of the reduced phosphorylation of PER in the new tim mutant appears to result from the cytoplasmic localization of PER. Interestingly, mutating a threonine near the original mutation produces similar phenotypes, raising the possibility that defective phosphorylation is the basis of TIM dysfunction in the novel tim mutant. We also show that a stable form of PER is cytoplasmic in tim-null flies. These studies establish an essential role of TIM in the timed nuclear entry of PER. PMID:21734289

  16. PU.1 affects proliferation of the human acute myeloid leukemia U937 cell line by directly regulating MEIS1

    PubMed Central

    ZHOU, JING; ZHANG, XIAOFENG; WANG, YUHUA; GUAN, YINGHUI

    2015-01-01

    The transcription factor PU.1 is a member of the ETS family, which is expressed in a wide variety of hematopoietic lineages. Accumulating evidence has indicated that PU.1 plays a key role in hematopoiesis, and reduced expression of PU.1 leads to the pathogenesis of human myeloid leukemia. As a multi-functional factor, PU.1 is also required for mixed lineage leukemia (MLL) stem cell potential and the development of MLL. However, the function of PU.1 in human non-MLL leukemia and its molecular mechanism remains poorly understood. In the present study, PU.1 siRNA was demonstrated to efficiently inhibit the transcription level of oncogene MEIS1 in the human acute myeloid non-MLL leukemia U937 cell line. In addition, PU.1, as a positive regulator of MEIS1, performed a crucial role in maintaining cell proliferation. Using electrophoretic mobility shift assay, chromatin immunoprecipitation analysis and luciferase reporter assay, previously unexplored evidence that PU.1 activated the MEIS1 promoter through a conserved binding motif in vitro and in vivo was further defined. Overall, the present study provides insight into the molecular mechanism of the contribution of PU.1 to the pathogenesis of non-MLL U937 cells, which is mediated by direct regulation of MEIS1 transcription. The present data reveal the possibility of developing an alternative therapy for non-MLL leukemia by targeting PU.1-mediated MEIS1 gene activation. PMID:26622774

  17. Down-regulated FSTL5 promotes cell proliferation and survival by affecting Wnt/β-catenin signaling in hepatocellular carcinoma

    PubMed Central

    Zhang, Dengyong; Ma, Xiang; Sun, Wanliang; Cui, Peiyuan; Lu, Zheng

    2015-01-01

    Follistatin-like 5 (FSTL5), a member of the follistatin family of genes, encodes a secretory glycoprotein. Previous study revealed that it might play a suppressive role in hepatocellular carcinoma (HCC). However, its clinical significances, biological functions and molecular mechanisms in HCC development are poorly understood. To gain insight to the functions of FSTL5 in HCC, We examined FSTL5 expression pattern in 117 HCC tissue samples. The results of immunohistochemical staining analysis showed that FSTL5 is more commonly down-regulated in HCC compared to adjacent tissues and further clinicopathological analysis showed that its expression level is closely correlated with tumor size, TNM stage, local infiltration and patient prognosis. Both gain function assays and recombinant human FSTL5 protein treatment assays in vitro revealed that over-expressing FSTL5 could inhibit the abilities of cancer cell proliferation and survival. Further, we found that those effects on HCC growth and survival are associated with Wnt/β-catenin signaling. Taken together, all of our results validate that FSTL5 plays a suppressive role in HCC and suggest that down-regulated FSTL5 could elevate abilities of growth and survival of HCC cells by activation of Wnt/β-catenin signaling. PMID:26045876

  18. Review of uncertainty sources affecting the long-term predictions of space debris evolutionary models

    NASA Astrophysics Data System (ADS)

    Dolado-Perez, J. C.; Pardini, Carmen; Anselmo, Luciano

    2015-08-01

    Since the launch of Sputnik-I in 1957, the amount of space debris in Earth's orbit has increased continuously. Historically, besides abandoned intact objects (spacecraft and orbital stages), the primary sources of space debris in Earth's orbit were (i) accidental and intentional break-ups which produced long-lasting debris and (ii) debris released intentionally during the operation of launch vehicle orbital stages and spacecraft. In the future, fragments generated by collisions are expected to become a significant source as well. In this context, and from a purely mathematical point of view, the orbital debris population in Low Earth Orbit (LEO) should be intrinsically unstable, due to the physics of mutual collisions and the relative ineffectiveness of natural sink mechanisms above~700 km. Therefore, the real question should not be "if", but "when" the exponential growth of the space debris population is supposed to start. From a practical point of view, and in order to answer the previous question, since the end of the 1980's several sophisticated long-term debris evolutionary models have been developed. Unfortunately, the predictions performed with such models, in particular beyond a few decades, are affected by considerable uncertainty. Such uncertainty comes from a relative important number of variables that being either under the partial control or completely out of the control of modellers, introduce a variability on the long-term simulation of the space debris population which cannot be captured with standard Monte Carlo statistics. The objective of this paper is to present and discuss many of the uncertainty sources affecting the long-term predictions done with evolutionary models, in order to serve as a roadmap for the uncertainty and the statistical robustness analysis of the long-term evolution of the space debris population.

  19. Seemingly irrational driving behavior model: The effect of habit strength and anticipated affective reactions.

    PubMed

    Chung, Yi-Shih

    2015-09-01

    An increasing amount of evidence suggests that aberrant driving behaviors are not entirely rational. On the basis of the dual-process theory, this study postulates that drivers may learn to perform irrational aberrant driving behaviors, and these behaviors could be derived either from a deliberate or an intuitive decision-making approach. Accordingly, a seemingly irrational driving behavior model is proposed; in this model, the theory of planned behavior (TPB) was adopted to represent the deliberate decision-making mechanism, and habit strength was incorporated to reflect the intuitive decision process. A multiple trivariate mediation structure was designed to reflect the process through which driving behaviors are learned. Anticipated affective reactions (AARs) were further included to examine the effect of affect on aberrant driving behaviors. Considering the example of speeding behaviors, this study developed scales and conducted a two-wave survey of students in two departments at a university in Northern Taiwan. The analysis results show that habit strength consists of multiple aspects, and frequency of past behavior cannot be a complete repository for accumulating habit strength. Habit strength appeared to be a crucial mediator between intention antecedents (e.g., attitude) and the intention itself. Including habit strength in the TPB model enhanced the explained variance of speeding intention by 26.7%. In addition, AARs were different from attitudes; particularly, young drivers tended to perform speeding behaviors to reduce negative feelings such as regret. The proposed model provides an effective alternative approach for investigating aberrant driving behaviors; corresponding countermeasures are discussed. PMID:26056969

  20. How absent negativity relates to affect and motivation: an integrative relief model

    PubMed Central

    Deutsch, Roland; Smith, Kevin J. M.; Kordts-Freudinger, Robert; Reichardt, Regina

    2015-01-01

    The present paper concerns the motivational underpinnings and behavioral correlates of the prevention or stopping of negative stimulation – a situation referred to as relief. Relief is of great theoretical and applied interest. Theoretically, it is tied to theories linking affect, emotion, and motivational systems. Importantly, these theories make different predictions regarding the association between relief and motivational systems. Moreover, relief is a prototypical antecedent of counterfactual emotions, which involve specific cognitive processes compared to factual or mere anticipatory emotions. Practically, relief may be an important motivator of addictive and phobic behaviors, self destructive behaviors, and social influence. In the present paper, we will first provide a review of conflicting conceptualizations of relief. We will then present an integrative relief model (IRMO) that aims at resolving existing theoretical conflicts. We then review evidence relevant to distinctive predictions regarding the moderating role of various procedural features of relief situations. We conclude that our integrated model results in a better understanding of existing evidence on the affective and motivational underpinnings of relief, but that further evidence is needed to come to a more comprehensive evaluation of the viability of IRMO. PMID:25806008

  1. Seasonal habitat suitability modeling and factors affecting the distribution of Asian Houbara in East Iran.

    PubMed

    Haghania, Ali; Aliabadian, Mansour; Sarhangzadeh, Jalil; Setoodehc, Ahad

    2016-08-01

    In this study, maximum entropy models were developed in four seasons to evaluate habitat suitability and factors affecting Asian Houbara in Iran. Environmental variables used in modeling consisted of 42 environmental and climate variables for Nayband wildlife refuge and 36 environmental and climate variables for Petregan protected area. Also, seasonal overlap area were obtained using the ENM TOOLS software. The results showed that the most important factors affecting habitat suitability of the Asian Houbara in all seasons included the ratio of distance to hill, the type of Artemisia-Gymnocarpus, distance to the slope (8-12%) in the Nayband wildlife refuge, distance to the type of Artemisia aucheri, distance to the Land Passion, and distance to the dry land farming in the Petregan region. In summer, the most suitable habitat is Nayband but is Petergan during fall-winter. there is maximum overlap in summer, and the least overlap in the spring these areas. The results of this study can be used as a valuable tool in implementing conservation and management strategies, in order to increase desirable habitats in the eastern part of Iran. PMID:27570839

  2. Improved Dynamic Modeling of the Cascade Distillation Subsystem and Analysis of Factors Affecting Its Performance

    NASA Technical Reports Server (NTRS)

    Perry, Bruce A.; Anderson, Molly S.

    2015-01-01

    The Cascade Distillation Subsystem (CDS) is a rotary multistage distiller being developed to serve as the primary processor for wastewater recovery during long-duration space missions. The CDS could be integrated with a system similar to the International Space Station Water Processor Assembly to form a complete water recovery system for future missions. A preliminary chemical process simulation was previously developed using Aspen Custom Modeler® (ACM), but it could not simulate thermal startup and lacked detailed analysis of several key internal processes, including heat transfer between stages. This paper describes modifications to the ACM simulation of the CDS that improve its capabilities and the accuracy of its predictions. Notably, the modified version can be used to model thermal startup and predicts the total energy consumption of the CDS. The simulation has been validated for both NaC1 solution and pretreated urine feeds and no longer requires retuning when operating parameters change. The simulation was also used to predict how internal processes and operating conditions of the CDS affect its performance. In particular, it is shown that the coefficient of performance of the thermoelectric heat pump used to provide heating and cooling for the CDS is the largest factor in determining CDS efficiency. Intrastage heat transfer affects CDS performance indirectly through effects on the coefficient of performance.

  3. How absent negativity relates to affect and motivation: an integrative relief model.

    PubMed

    Deutsch, Roland; Smith, Kevin J M; Kordts-Freudinger, Robert; Reichardt, Regina

    2015-01-01

    The present paper concerns the motivational underpinnings and behavioral correlates of the prevention or stopping of negative stimulation - a situation referred to as relief. Relief is of great theoretical and applied interest. Theoretically, it is tied to theories linking affect, emotion, and motivational systems. Importantly, these theories make different predictions regarding the association between relief and motivational systems. Moreover, relief is a prototypical antecedent of counterfactual emotions, which involve specific cognitive processes compared to factual or mere anticipatory emotions. Practically, relief may be an important motivator of addictive and phobic behaviors, self destructive behaviors, and social influence. In the present paper, we will first provide a review of conflicting conceptualizations of relief. We will then present an integrative relief model (IRMO) that aims at resolving existing theoretical conflicts. We then review evidence relevant to distinctive predictions regarding the moderating role of various procedural features of relief situations. We conclude that our integrated model results in a better understanding of existing evidence on the affective and motivational underpinnings of relief, but that further evidence is needed to come to a more comprehensive evaluation of the viability of IRMO. PMID:25806008

  4. Principles of microRNA Regulation Revealed Through Modeling microRNA Expression Quantitative Trait Loci

    PubMed Central

    Budach, Stefan; Heinig, Matthias; Marsico, Annalisa

    2016-01-01

    Extensive work has been dedicated to study mechanisms of microRNA-mediated gene regulation. However, the transcriptional regulation of microRNAs themselves is far less well understood, due to difficulties determining the transcription start sites of transient primary transcripts. This challenge can be addressed using expression quantitative trait loci (eQTLs) whose regulatory effects represent a natural source of perturbation of cis-regulatory elements. Here we used previously published cis-microRNA-eQTL data for the human GM12878 cell line, promoter predictions, and other functional annotations to determine the relationship between functional elements and microRNA regulation. We built a logistic regression model that classifies microRNA/SNP pairs into eQTLs or non-eQTLs with 85% accuracy; shows microRNA-eQTL enrichment for microRNA precursors, promoters, enhancers, and transcription factor binding sites; and depletion for repressed chromatin. Interestingly, although there is a large overlap between microRNA eQTLs and messenger RNA eQTLs of host genes, 74% of these shared eQTLs affect microRNA and host expression independently. Considering microRNA-only eQTLs we find a significant enrichment for intronic promoters, validating the existence of alternative promoters for intragenic microRNAs. Finally, in line with the GM12878 cell line derived from B cells, we find genome-wide association (GWA) variants associated to blood-related traits more likely to be microRNA eQTLs than random GWA and non-GWA variants, aiding the interpretation of GWA results. PMID:27260304

  5. A Model for Self-Regulated Distance Language Learning

    ERIC Educational Resources Information Center

    Andrade, Maureen S.; Bunker, Ellen L.

    2009-01-01

    The role of learner autonomy and self-regulated learning in distance education has received much attention. The application of these concepts impacts course design and, potentially, learner achievement. In the case of distance language learning, course designers must consider not only how to help learners gain communicative competence but also…

  6. Ecosystem carbon storage capacity as affected by disturbance regimes: A general theoretical model

    NASA Astrophysics Data System (ADS)

    Weng, Ensheng; Luo, Yiqi; Wang, Weile; Wang, Han; Hayes, Daniel J.; McGuire, A. David; Hastings, Alan; Schimel, David S.

    2012-09-01

    Disturbances have been recognized as a key factor shaping terrestrial ecosystem states and dynamics. A general model that quantitatively describes the relationship between carbon storage and disturbance regime is critical for better understanding large scale terrestrial ecosystem carbon dynamics. We developed a model (REGIME) to quantify ecosystem carbon storage capacities (E[x]) under varying disturbance regimes with an analytical solution E[x] = U · τE · ?, where U is ecosystem carbon influx, τE is ecosystem carbon residence time, and τ1 is the residence time of the carbon pool affected by disturbances (biomass pool in this study). The disturbance regime is characterized by the mean disturbance interval (λ) and the mean disturbance severity (s). It is a Michaelis-Menten-type equation illustrating the saturation of carbon content with mean disturbance interval. This model analytically integrates the deterministic ecosystem carbon processes with stochastic disturbance events to reveal a general pattern of terrestrial carbon dynamics at large scales. The model allows us to get a sense of the sensitivity of ecosystems to future environmental changes just by a few calculations. According to the REGIME model, for example, approximately 1.8 Pg C will be lost in the high-latitude regions of North America (>45°N) if fire disturbance intensity increases around 5.7 time the current intensity to the end of the twenty-first century, which will require around 12% increases in net primary productivity (NPP) to maintain stable carbon stocks. If the residence time decreased 10% at the same time additional 12.5% increases in NPP are required to keep current C stocks. The REGIME model also lays the foundation for analytically modeling the interactions between deterministic biogeochemical processes and stochastic disturbance events.

  7. Ecosystem carbon storage capacity as affected by disturbance regimes: a general theoretical model

    NASA Astrophysics Data System (ADS)

    Weng, E.; Luo, Y.; Wang, W.; Wang, H.; Hayes, D. J.; McGuire, A. D.; Hastings, A.; Schimel, D.

    2012-12-01

    Disturbances have been recognized as a key factor shaping terrestrial ecosystem states and dynamics. A general model that quantitatively describes the relationship between carbon storage and disturbance regime is critical for better understanding large scale terrestrial ecosystem carbon dynamics. We developed a model (REGIME) to quantify ecosystem carbon storage capacities (E[x]) under varying disturbance regimes with an analytical solution E[x]=UτE λ/(λ+sτ1) , where U is ecosystem carbon influx, τE is ecosystem carbon residence time, and τ1 is the residence time of the carbon pool affected by disturbances (biomass pool in this study). The disturbance regime is characterized by the mean disturbance interval (λ) and the mean disturbance severity (s). It is a Michaelis-Menten type equation illustrating the saturation of carbon content with mean disturbance interval. This model analytically integrates the deterministic ecosystem carbon processes with stochastic disturbance events to reveal a general pattern of terrestrial carbon dynamics at large scales. The model allows us to get a sense of the sensitivity of ecosystems to future environmental changes just by a few calculations. According to the REGIME model , for example, approximately 1.8 Pg C will be lost in the high latitude regions of North America (>45°N) if fire disturbance intensity increases around 5.7 time the current intensity to the end of 21st century, which will require around 12% increases in NPP to maintain stable carbon stocks. If the residence time decreased 10% at the same time additional 12.5% increases in NPP are required to keep current C stocks. The REGIME model also lays the foundation for analytically modeling the interactions between deterministic biogeochemical processes and stochastic disturbance events.

  8. A coupled mechanical and chemical damage model for concrete affected by alkali–silica reaction

    SciTech Connect

    Pignatelli, Rossella; Comi, Claudia; Monteiro, Paulo J.M.

    2013-11-15

    To model the complex degradation phenomena occurring in concrete affected by alkali–silica reaction (ASR), we formulate a poro-mechanical model with two isotropic internal variables: the chemical and the mechanical damage. The chemical damage, related to the evolution of the reaction, is caused by the pressure generated by the expanding ASR gel on the solid concrete skeleton. The mechanical damage describes the strength and stiffness degradation induced by the external loads. As suggested by experimental results, degradation due to ASR is considered to be localized around reactive sites. The effect of the degree of saturation and of the temperature on the reaction development is also modeled. The chemical damage evolution is calibrated using the value of the gel pressure estimated by applying the electrical diffuse double-layer theory to experimental values of the surface charge density in ASR gel specimens reported in the literature. The chemo-damage model is first validated by simulating expansion tests on reactive specimens and beams; the coupled chemo-mechanical damage model is then employed to simulate compression and flexure tests results also taken from the literature. -- Highlights: •Concrete degradation due to ASR in variable environmental conditions is modeled. •Two isotropic internal variables – chemical and mechanical damage – are introduced. •The value of the swelling pressure is estimated by the diffuse double layer theory. •A simplified scheme is proposed to relate macro- and microscopic properties. •The chemo-mechanical damage model is validated by simulating tests in literature.

  9. Ecosystem carbon storage capacity as affected by disturbance regimes: A general theoretical model

    SciTech Connect

    Weng, Ensheng; Luo, Yiqi; Wang, Weile; Wang, Han; Hayes, Daniel J; McGuire, A. David; Hastings, Alan; Schimel, David

    2012-01-01

    Disturbances have been recognized as a key factor shaping terrestrial ecosystem states and dynamics. A general model that quantitatively describes the relationship between carbon storage and disturbance regime is critical for better understanding large scale terrestrial ecosystem carbon dynamics. We developed a model (REGIME) to quantify ecosystem carbon storage capacities (E[x]) under varying disturbance regimes with an analytical solution E[x] = U {center_dot} {tau}{sub E} {center_dot} {lambda}{lambda} + s {tau} 1, where U is ecosystem carbon influx, {tau}{sub E} is ecosystem carbon residence time, and {tau}{sub 1} is the residence time of the carbon pool affected by disturbances (biomass pool in this study). The disturbance regime is characterized by the mean disturbance interval ({lambda}) and the mean disturbance severity (s). It is a Michaelis-Menten-type equation illustrating the saturation of carbon content with mean disturbance interval. This model analytically integrates the deterministic ecosystem carbon processes with stochastic disturbance events to reveal a general pattern of terrestrial carbon dynamics at large scales. The model allows us to get a sense of the sensitivity of ecosystems to future environmental changes just by a few calculations. According to the REGIME model, for example, approximately 1.8 Pg C will be lost in the high-latitude regions of North America (>45{sup o} N) if fire disturbance intensity increases around 5.7 time the current intensity to the end of the twenty-first century, which will require around 12% increases in net primary productivity (NPP) to maintain stable carbon stocks. If the residence time decreased 10% at the same time additional 12.5% increases in NPP are required to keep current C stocks. The REGIME model also lays the foundation for analytically modeling the interactions between deterministic biogeochemical processes and stochastic disturbance events.

  10. Multistate modeling of habitat dynamics: Factors affecting Florida scrub transition probabilities

    USGS Publications Warehouse

    Breininger, D.R.; Nichols, J.D.; Duncan, B.W.; Stolen, Eric D.; Carter, G.M.; Hunt, D.K.; Drese, J.H.

    2010-01-01

    Many ecosystems are influenced by disturbances that create specific successional states and habitat structures that species need to persist. Estimating transition probabilities between habitat states and modeling the factors that influence such transitions have many applications for investigating and managing disturbance-prone ecosystems. We identify the correspondence between multistate capture-recapture models and Markov models of habitat dynamics. We exploit this correspondence by fitting and comparing competing models of different ecological covariates affecting habitat transition probabilities in Florida scrub and flatwoods, a habitat important to many unique plants and animals. We subdivided a large scrub and flatwoods ecosystem along central Florida's Atlantic coast into 10-ha grid cells, which approximated average territory size of the threatened Florida Scrub-Jay (Aphelocoma coerulescens), a management indicator species. We used 1.0-m resolution aerial imagery for 1994, 1999, and 2004 to classify grid cells into four habitat quality states that were directly related to Florida Scrub-Jay source-sink dynamics and management decision making. Results showed that static site features related to fire propagation (vegetation type, edges) and temporally varying disturbances (fires, mechanical cutting) best explained transition probabilities. Results indicated that much of the scrub and flatwoods ecosystem was resistant to moving from a degraded state to a desired state without mechanical cutting, an expensive restoration tool. We used habitat models parameterized with the estimated transition probabilities to investigate the consequences of alternative management scenarios on future habitat dynamics. We recommend this multistate modeling approach as being broadly applicable for studying ecosystem, land cover, or habitat dynamics. The approach provides maximum-likelihood estimates of transition parameters, including precision measures, and can be used to assess

  11. EphrinB2 affects apical constriction in Xenopus embryos and is regulated by ADAM10 and flotillin-1

    NASA Astrophysics Data System (ADS)

    Ji, Yon Ju; Hwang, Yoo-Seok; Mood, Kathleen; Cho, Hee-Jun; Lee, Hyun-Shik; Winterbottom, Emily; Cousin, Hélène; Daar, Ira O.

    2014-03-01

    The Eph/ephrin signalling pathways have a critical function in cell adhesion and repulsion, and thus play key roles in various morphogenetic events during development. Here we show that a decrease in ephrinB2 protein causes neural tube closure defects during Xenopus laevis embryogenesis. Such a decrease in ephrinB2 protein levels is observed on the loss of flotillin-1 scaffold protein, a newly identified ephrinB2-binding partner. This dramatic decline in ephrinB2 protein levels on the absence of flotillin-1 expression is specific, and is partly the result of an increased susceptibility to cleavage by the metalloprotease ADAM10. These findings indicate that flotillin-1 regulates ephrinB2 protein levels through ADAM10, and is required for appropriate neural tube morphogenesis in the Xenopus embryo.

  12. De-regulation of gene expression and alternative splicing affects distinct cellular pathways in the aging hippocampus

    PubMed Central

    Stilling, Roman M.; Benito, Eva; Gertig, Michael; Barth, Jonas; Capece, Vincenzo; Burkhardt, Susanne; Bonn, Stefan; Fischer, Andre

    2014-01-01

    Aging is accompanied by gradually increasing impairment of cognitive abilities and constitutes the main risk factor of neurodegenerative conditions like Alzheimer's disease (AD). The underlying mechanisms are however not well understood. Here we analyze the hippocampal transcriptome of young adult mice and two groups of mice at advanced age using RNA sequencing. This approach enabled us to test differential expression of coding and non-coding transcripts, as well as differential splicing and RNA editing. We report a specific age-associated gene expression signature that is associated with major genetic risk factors for late-onset AD (LOAD). This signature is dominated by neuroinflammatory processes, specifically activation of the complement system at the level of increased gene expression, while de-regulation of neuronal plasticity appears to be mediated by compromised RNA splicing. PMID:25431548

  13. Ego depletion--is it all in your head? implicit theories about willpower affect self-regulation.

    PubMed

    Job, Veronika; Dweck, Carol S; Walton, Gregory M

    2010-11-01

    Much recent research suggests that willpower--the capacity to exert self-control--is a limited resource that is depleted after exertion. We propose that whether depletion takes place or not depends on a person's belief about whether willpower is a limited resource. Study 1 found that individual differences in lay theories about willpower moderate ego-depletion effects: People who viewed the capacity for self-control as not limited did not show diminished self-control after a depleting experience. Study 2 replicated the effect, manipulating lay theories about willpower. Study 3 addressed questions about the mechanism underlying the effect. Study 4, a longitudinal field study, found that theories about willpower predict change in eating behavior, procrastination, and self-regulated goal striving in depleting circumstances. Taken together, the findings suggest that reduced self-control after a depleting task or during demanding periods may reflect people's beliefs about the availability of willpower rather than true resource depletion. PMID:20876879

  14. POD-1/TCF21 Reduces SHP Expression, Affecting LRH-1 Regulation and Cell Cycle Balance in Adrenocortical and Hepatocarcinoma Tumor Cells

    PubMed Central

    França, Monica Malheiros; Ferraz-de-Souza, Bruno; Lerario, Antonio Marcondes; Fragoso, Maria Candida Barisson Villares; Lotfi, Claudimara Ferini Pacicco

    2015-01-01

    POD-1/TCF21 may play a crucial role in adrenal and gonadal homeostasis and represses Sf-1/SF-1 expression in adrenocortical tumor cells. SF-1 and LRH-1 are members of the Fzt-F1 subfamily of nuclear receptors. LRH-1 is involved in several biological processes, and both LRH-1 and its repressor SHP are involved in many types of cancer. In order to assess whether POD-1 can regulate LRH-1 via the same mechanism that regulates SF-1, we analyzed the endogenous mRNA levels of POD-1, SHP, and LRH-1 in hepatocarcinoma and adrenocortical tumor cells using qRT-PCR. Hereafter, these tumor cells were transiently transfected with pCMVMycPod-1, and the effect of POD-1 overexpression on E-box elements in the LRH-1 and SHP promoter region were analyzed by ChIP assay. Also, Cyclin E1 protein expression was analyzed to detect cell cycle progression. We found that POD-1 overexpression significantly decreased SHP/SHP mRNA and protein levels through POD-1 binding to the E-box sequence in the SHP promoter. Decreased SHP expression affected LRH-1 regulation and increased Cyclin E1. These findings show that POD-1/TCF21 regulates SF-1 and LRH-1 by distinct mechanisms, contributing to the understanding of POD-1 involvement and its mechanisms of action in adrenal and liver tumorigenesis, which could lead to the discovery of relevant biomarkers. PMID:26421305

  15. CebR as a master regulator for cellulose/cellooligosaccharide catabolism affects morphological development in Streptomyces griseus.

    PubMed

    Marushima, Kazuya; Ohnishi, Yasuo; Horinouchi, Sueharu

    2009-10-01

    Streptomyces griseus mutants exhibiting deficient glucose repression of beta-galactosidase activity on lactose-containing minimal medium supplemented with a high concentration of glucose were isolated. One of these mutants had a 12-bp deletion in cebR, which encodes a LacI/GalR family regulator. Disruption of cebR in the wild-type strain caused the same phenotype as the mutant, indicating that CebR is required for glucose repression of beta-galactosidase activity. Recombinant CebR protein bound to a 14-bp inverted-repeat sequence (designated the CebR box) present in the promoter regions of cebR and the putative cellobiose utilization operon, cebEFG-bglC. The DNA-binding activity of CebR was impaired by cellooligosaccharides, including cellobiose, cellotriose, cellotetraose, cellopentaose, and cellohexaose. In agreement with this observation, transcription from the cebE and cebR promoters was greatly enhanced by the addition of cellobiose to the medium. Seven other genes containing one or two CebR boxes in their upstream regions were found in the S. griseus genome. Five of these genes encode putative secreted proteins: two cellulases, a cellulose-binding protein, a pectate lyase, and a protein of unknown function. These five genes and cebEFG-bglC were transcribed at levels 4 to 130 times higher in the DeltacebR mutant than in the wild-type strain, as determined by quantitative reverse transcription-PCR. These findings indicate that CebR is a master regulator of cellulose/cellooligosaccharide catabolism. Unexpectedly, the DeltacebR mutant formed very few aerial hyphae on lactose-containing medium, demonstrating a link between carbon source utilization and morphological development. PMID:19648249

  16. Mutations That Affect Transcription and Cyclic Amp-Crp Regulation of the Adenylate Cyclase Gene (Cya) of Salmonella Typhimurium

    PubMed Central

    Fandl, J. P.; Thorner, L. K.; Artz, S. W.

    1990-01-01

    We studied the expression of the cya promoter(s) in cya-lac fusion strains of Salmonella typhimurium and demonstrated cAMP receptor protein (CRP)-dependent repression by cAMP. Expression of cya was reduced about fourfold in cultures grown in acetate minimal medium as compared to cultures grown in glucose-6-phosphate minimal medium. Expression of cya was also reduced about fourfold by addition of 5 mM cAMP to cultures grown in glucose minimal medium. We constructed in vitro deletion and insertion mutations altering a major cya promoter (P2) and a putative CRP binding site overlapping P2. These mutations were recombined into the chromosome by allele replacement with M13mp::cya recombinant phages and the regulation of the mutant promoters was analyzed. A 4-bp deletion of the CRP binding site and a 4-bp insertion in this site nearly eliminated repression by cAMP. A mutant with the P2 promoter and the CRP binding site both deleted exhibited an 80% reduction in cya expression; the 20% residual expression was insensitive to cAMP repression. This mutant retained a Cya(+) phenotype. Taken together, the results establish that the cya gene is transcribed from multiple promoters one of which, P2, is negatively regulated by the cAMP-CRP complex. Correction for the contribution to transcription by the cAMP-CRP nonregulated cya promoters indicates that the P2 promoter is repressed at least eightfold by cAMP-CRP. PMID:2168849

  17. Decision analysis and risk models for land development affecting infrastructure systems.

    PubMed

    Thekdi, Shital A; Lambert, James H

    2012-07-01

    Coordination and layering of models to identify risks in complex systems such as large-scale infrastructure of energy, water, and transportation is of current interest across application domains. Such infrastructures are increasingly vulnerable to adjacent commercial and residential land development. Land development can compromise the performance of essential infrastructure systems and increase the costs of maintaining or increasing performance. A risk-informed approach to this topic would be useful to avoid surprise, regret, and the need for costly remedies. This article develops a layering and coordination of models for risk management of land development affecting infrastructure systems. The layers are: system identification, expert elicitation, predictive modeling, comparison of investment alternatives, and implications of current decisions for future options. The modeling layers share a focus on observable factors that most contribute to volatility of land development and land use. The relevant data and expert evidence include current and forecasted growth in population and employment, conservation and preservation rules, land topography and geometries, real estate assessments, market and economic conditions, and other factors. The approach integrates to a decision framework of strategic considerations based on assessing risk, cost, and opportunity in order to prioritize needs and potential remedies that mitigate impacts of land development to the infrastructure systems. The approach is demonstrated for a 5,700-mile multimodal transportation system adjacent to 60,000 tracts of potential land development. PMID:22050390

  18. Does Mutual Interference Affect the Feeding Rate of Aphidophagous Coccinellids? A Modeling Perspective.

    PubMed

    Papanikolaou, Nikos E; Demiris, Nikos; Milonas, Panagiotis G; Preston, Simon; Kypraios, Theodore

    2016-01-01

    Mutual interference involves direct interactions between individuals of the same species that may alter their foraging success. Larvae of aphidophagous coccinellids typically stay within a patch during their lifetime, displaying remarkable aggregation to their prey. Thus, as larvae are exposed to each other, frequent encounters may affect their foraging success. A study was initiated in order to determine the effect of mutual interference in the coccinellids' feeding rate. One to four 4th larval instars of the fourteen-spotted ladybird beetle Propylea quatuordecimpunctata were exposed for 6 hours into plastic containers with different densities of the black bean aphid, Aphis fabae, on potted Vicia faba plants. The data were used to fit a purely prey-dependent Holling type II model and its alternatives which account for interference competition and have thus far been underutilized, i.e. the Beddington-DeAngelis, the Crowley-Martin and a modified Hassell-Varley model. The Crowley-Martin mechanistic model appeared to be slightly better among the competing models. The results showed that although the feeding rate became approximately independent of predator density at high prey density, some predator dependence in the coccinellid's functional response was observed at the low prey-high predator density combination. It appears that at low prey densities, digestion breaks are negligible so that the predators do waste time interfering with each other, whereas at high prey densities time loss during digestion breaks may fully accommodate the cost of interference, so that the time cost may be negligible. PMID:26756980

  19. Increasing attendance for psychotherapy: implementation intentions and the self-regulation of attendance-related negative affect.

    PubMed

    Sheeran, Paschal; Aubrey, Richard; Kellett, Stephen

    2007-12-01

    The present study evaluated an implementation intention intervention that aimed to increase attendance at scheduled, initial appointments for psychotherapy by helping clients to manage negative feelings about attendance. Participants received a postal questionnaire that measured their views about attending psychotherapy. One half of the sample was randomly assigned to an implementation intention induction that was embedded in the questionnaire. Intention-to-treat analysis (N=390) indicated that participants who formed implementation intentions were more likely to attend compared to controls (75% vs. 63%), and this effect was even stronger among participants who returned the questionnaire (83% vs. 57%). Whereas anticipated affective costs (e.g., shame) had a negative impact on attendance for most participants, this effect was attenuated when participants formed implementation intentions and perceived that attendance would be beneficial. Thus, implementation intention formation can help clients to deal effectively with negative feelings that might otherwise prevent them attending their first psychotherapy appointment. PMID:18085903

  20. A Mixed Model to Disentangle Variance and Serial Autocorrelation in Affective Instability Using Ecological Momentary Assessment Data.

    PubMed

    Vansteelandt, Kristof; Verbeke, Geert

    2016-01-01

    Affective instability, the tendency to experience emotions that fluctuate frequently and intensively over time, is a core feature of several mental disorders including borderline personality disorder. Currently, affect is often measured with Ecological Momentary Assessment protocols, which yield the possibility to quantify the instability of affect over time. A number of linear mixed models are proposed to examine (diagnostic) group differences in affective instability. The models contribute to the existing literature by estimating simultaneously both the variance and serial dependency component of affective instability when observations are unequally spaced in time with the serial autocorrelation (or emotional inertia) declining as a function of the time interval between observations. In addition, the models can eliminate systematic trends, take between subject differences into account and test for (diagnostic) group differences in serial autocorrelation, short-term as well as long-term affective variability. The usefulness of the models is illustrated in a study on diagnostic group differences in affective instability in the domain of eating disorders. Limitations of the model are that they pertain to group (and not individual) differences and do not focus explicitly on circadian rhythms or cycles in affect. PMID:27191204

  1. The Chromatin-binding Protein HMGN1 Regulates the Expression of Methyl CpG-binding Protein 2 (MECP2) and Affects the Behavior of Mice*

    PubMed Central

    Abuhatzira, Liron; Shamir, Alon; Schones, Dustin E.; Schäffer, Alejandro A.; Bustin, Michael

    2011-01-01

    High mobility group N1 protein (HMGN1), a nucleosomal-binding protein that affects the structure and function of chromatin, is encoded by a gene located on chromosome 21 and is overexpressed in Down syndrome, one of the most prevalent genomic disorders. Misexpression of HMGN1 affects the cellular transcription profile; however, the biological function of this protein is still not fully understood. We report that HMGN1 modulates the expression of methyl CpG-binding protein 2 (MeCP2), a DNA-binding protein known to affect neurological functions including autism spectrum disorders, and whose alterations in HMGN1 levels affect the behavior of mice. Quantitative PCR and Western analyses of cell lines and brain tissues from mice that either overexpress or lack HMGN1 indicate that HMGN1 is a negative regulator of MeCP2 expression. Alterations in HMGN1 levels lead to changes in chromatin structure and histone modifications in the MeCP2 promoter. Behavior analyses by open field test, elevated plus maze, Reciprocal Social Interaction, and automated sociability test link changes in HMGN1 levels to abnormalities in activity and anxiety and to social deficits in mice. Targeted analysis of the Autism Genetic Resource Exchange genotype collection reveals a non-random distribution of genotypes within 500 kbp of HMGN1 in a region affecting its expression in families predisposed to autism spectrum disorders. Our results reveal that HMGN1 affects the behavior of mice and suggest that epigenetic changes resulting from altered HMGN1 levels could play a role in the etiology of neurodevelopmental disorders. PMID:22009741

  2. How historic simulation-observation discrepancy affects future warming projections in a very large model ensemble

    NASA Astrophysics Data System (ADS)

    Goodwin, Philip

    2016-01-01

    Projections of future climate made by model-ensembles have credibility because the historic simulations by these models are consistent with, or near-consistent with, historic observations. However, it is not known how small inconsistencies between the ranges of observed and simulated historic climate change affects the future projections made by a model ensemble. Here, the impact of historical simulation-observation inconsistencies on future warming projections is quantified in a 4-million member Monte Carlo ensemble from a new efficient Earth System Model (ESM). Of the 4-million ensemble members, a subset of 182,500 are consistent with historic ranges of warming, heat uptake and carbon uptake simulated by the Climate Model Intercomparison Project 5 (CMIP5) ensemble. This simulation-consistent subset projects similar future warming ranges to the CMIP5 ensemble for all four RCP scenarios, indicating the new ESM represents an efficient tool to explore parameter space for future warming projections based on historic performance. A second subset of 14,500 ensemble members are consistent with historic observations for warming, heat uptake and carbon uptake. This observation-consistent subset projects a narrower range for future warming, with the lower bounds of projected warming still similar to CMIP5, but the upper warming bounds reduced by 20-35 %. These findings suggest that part of the upper range of twenty-first century CMIP5 warming projections may reflect historical simulation-observation inconsistencies. However, the agreement of lower bounds for projected warming implies that the likelihood of warming exceeding dangerous levels over the twenty-first century is unaffected by small discrepancies between CMIP5 models and observations.

  3. Neuromusculoskeletal Model Calibration Significantly Affects Predicted Knee Contact Forces for Walking.

    PubMed

    Serrancolí, Gil; Kinney, Allison L; Fregly, Benjamin J; Font-Llagunes, Josep M

    2016-08-01

    Though walking impairments are prevalent in society, clinical treatments are often ineffective at restoring lost function. For this reason, researchers have begun to explore the use of patient-specific computational walking models to develop more effective treatments. However, the accuracy with which models can predict internal body forces in muscles and across joints depends on how well relevant model parameter values can be calibrated for the patient. This study investigated how knowledge of internal knee contact forces affects calibration of neuromusculoskeletal model parameter values and subsequent prediction of internal knee contact and leg muscle forces during walking. Model calibration was performed using a novel two-level optimization procedure applied to six normal walking trials from the Fourth Grand Challenge Competition to Predict In Vivo Knee Loads. The outer-level optimization adjusted time-invariant model parameter values to minimize passive muscle forces, reserve actuator moments, and model parameter value changes with (Approach A) and without (Approach B) tracking of experimental knee contact forces. Using the current guess for model parameter values but no knee contact force information, the inner-level optimization predicted time-varying muscle activations that were close to experimental muscle synergy patterns and consistent with the experimental inverse dynamic loads (both approaches). For all the six gait trials, Approach A predicted knee contact forces with high accuracy for both compartments (average correlation coefficient r = 0.99 and root mean square error (RMSE) = 52.6 N medial; average r = 0.95 and RMSE = 56.6 N lateral). In contrast, Approach B overpredicted contact force magnitude for both compartments (average RMSE = 323 N medial and 348 N lateral) and poorly matched contact force shape for the lateral compartment (average r = 0.90 medial and -0.10 lateral). Approach B had statistically higher lateral

  4. The pan-deacetylase inhibitor panobinostat affects angiogenesis in hepatocellular carcinoma models via modulation of CTGF expression.

    PubMed

    Gahr, Susanne; Mayr, Christian; Kiesslich, Tobias; Illig, Romana; Neureiter, Daniel; Alinger, Beate; Ganslmayer, Marion; Wissniowski, Till; Fazio, Pietro Di; Montalbano, Roberta; Ficker, Joachim H; Ocker, Matthias; Quint, Karl

    2015-09-01

    Post-translational modifications of chromatin components are significantly involved in the regulation of tumor suppressor gene and oncogene expression. Connective tissue growth factor (CTGF) is an epigenetically regulated growth factor with functions in angiogenesis and cell-matrix interactions and plays a pivotal role in hepatocellular carcinoma (HCC). The pharmacologic inhibition of histone and protein deacetylases represents a new approach to interfere with pathways of apoptosis and angiogenesis. We investigated the effect of the pan-deacetylase inhibitor panobinostat (LBH589) on human HCC cell lines HepG2 (p53wt) and Hep3B (p53null) and in a subcutaneous xenograft model and explored the influence on angiogenesis. Specimens were characterized by quantitative real-time PCR. Protein was separated for western blotting against CTGF, VEGF, VEGF receptor-1 (VEGFR-1/FLT-1), VEGF receptor-2 (VEGFR-2/KDR), MAPK and phospho-MAPK. In vivo, HepG2 cells were xenografted to NMRI mice and treated with daily i.p. injections of 10 mg/kg panobinostat. After 1, 7 and 28 days, real-time PCR was performed. Immunohistochemistry and western blotting were examined after 28 days. An increased significant expression of CTGF was only seen after 24 h treatment with 0.1 µM panobinostat in HepG2 cells and Hep3B cells, whereas after 72 h treatment CTGF expression clearly decreased. In the xenografts, treatment with panobinostat showed a minimal CTGF expression after 1 day and 4 weeks, respectively. In vitro as well as in vivo, VEGF was not affected by panobinostat treatment at any time. In conclusion, panobinostat influences extracellular signaling cascades via CTGF-dependent pathways. PMID:26202945

  5. Mechanical regulation of cardiac muscle by coupling calcium kinetics with cross-bridge cycling: a dynamic model.

    PubMed

    Landesberg, A; Sideman, S

    1994-08-01

    This study describes the regulation of mechanical activity in the intact cardiac muscle, the effects of the free calcium transients and the mechanical constraints, and emphasizes the central role of the troponin complex in regulating muscle activity. A "loose coupling" between calcium binding to troponin and cross-bridge cycling is stipulated, allowing the existence of cross bridges in the strong conformation without having bound calcium on the neighboring troponin. The model includes two feedback mechanisms: 1) a positive feedback, or cooperativity, in which the cycling cross bridges affect the affinity of troponin for calcium, and 2) a negative mechanical feedback, where the filament-sliding velocity affects cross-bridge cycling. The model simulates the reported experimental force-length and force-velocity relationships at different levels of activation. The dependence of the shortening velocity on calcium concentration, sarcomere length, internal load, and rate of cross-bridge cycling is described analytically in agreement with reported data. Furthermore, the model provides an analytic solution for Hill's equation of the force-velocity relationship and for the phenomena of unloaded shortening velocity and force deficit. The model-calculated changes in free calcium in various mechanical conditions are in good agreement with the available experimental results. PMID:8067434

  6. Assessment of Intraindividual Variability in Positive and Negative Affect Using Latent State-Trait Model Analyses

    ERIC Educational Resources Information Center

    Yasuda, Tomoyuki; Lawrenz, Cathy; Whitlock, Rod Van; Lubin, Bernard; Lei, Pui-Wa

    2004-01-01

    Intraindividual variability in positive and negative affect was assessed by the positive affect (Contentment, Joy, Vigor, Love, and Excitement) and negative affect (Depression, Hostility, Anxiety, Agitation, and Social Anxiety) subscales of the state version of the Comprehensive Personality and Affect Scales (COPAS) during a 3-week period. Using…

  7. Melanoma Expressed-CD70 Is Regulated by RhoA and MAPK Pathways without Affecting Vemurafenib Treatment Activity

    PubMed Central

    Sarrabayrouse, Guillaume; Gallardo, Franck; Gence, Rémi; Tilkin-Mariamé, Anne-Françoise

    2016-01-01

    CD70 is a costimulatory molecule member of the Tumor Necrosis Factor family that is expressed on activated immune cells. Its ectopic expression has been described in several types of cancer cells including lymphomas, renal cell carcinomas and glioblastomas. We have recently described its expression in a part of tumor cells from the vast majority of melanoma biopsies and human melanoma cell lines, and found that CD70 expression decreased over time as the disease progressed. Here, we show that RhoA, BRAF and Mitogen Activating Protein Kinase pathways are involved in the positive transcriptional regulation of CD70 expression in melanomas. Interestingly, the clinical inhibitor of the common BRAF V600E/D variants, Vemurafenib (PLX-4032), which is currently used to treat melanoma patients with BRAF V600E/D-mutated metastatic melanomas, decreased CD70 expression in human CD70+ melanoma cell lines. This decrease was seen in melanoma cells both with and without the BRAFV600E/D mutation, although was less efficient in those lacking the mutation. But interestingly, by silencing CD70 in CD70+ melanoma cell lines we show that PLX-4032-induced melanoma cell killing and its inhibitory effect on MAPK pathway activation are unaffected by CD70 expression. Consequently, our work demonstrates that CD70 ectopic expression in melanomas is not a valuable biomarker to predict tumor cells sensitivity to BRAF V600 inhibitors. PMID:26828592

  8. Melanoma Expressed-CD70 Is Regulated by RhoA and MAPK Pathways without Affecting Vemurafenib Treatment Activity.

    PubMed

    Pich, Christine; Teiti, Iotefa; Sarrabayrouse, Guillaume; Gallardo, Franck; Gence, Rémi; Tilkin-Mariamé, Anne-Françoise

    2016-01-01

    CD70 is a costimulatory molecule member of the Tumor Necrosis Factor family that is expressed on activated immune cells. Its ectopic expression has been described in several types of cancer cells including lymphomas, renal cell carcinomas and glioblastomas. We have recently described its expression in a part of tumor cells from the vast majority of melanoma biopsies and human melanoma cell lines, and found that CD70 expression decreased over time as the disease progressed. Here, we show that RhoA, BRAF and Mitogen Activating Protein Kinase pathways are involved in the positive transcriptional regulation of CD70 expression in melanomas. Interestingly, the clinical inhibitor of the common BRAF V600E/D variants, Vemurafenib (PLX-4032), which is currently used to treat melanoma patients with BRAF V600E/D-mutated metastatic melanomas, decreased CD70 expression in human CD70+ melanoma cell lines. This decrease was seen in melanoma cells both with and without the BRAFV600E/D mutation, although was less efficient in those lacking the mutation. But interestingly, by silencing CD70 in CD70+ melanoma cell lines we show that PLX-4032-induced melanoma cell killing and its inhibitory effect on MAPK pathway activation are unaffected by CD70 expression. Consequently, our work demonstrates that CD70 ectopic expression in melanomas is not a valuable biomarker to predict tumor cells sensitivity to BRAF V600 inhibitors. PMID:26828592

  9. KCNQ1, KCNE2, and Na+-Coupled Solute Transporters Form Reciprocally Regulating Complexes that Affect Neuronal Excitability

    PubMed Central

    Abbott, Geoffrey W.; Tai, Kwok-Keung; Neverisky, Daniel; Hansler, Alex; Hu, Zhaoyang; Roepke, Torsten K.; Lerner, Daniel J.; Chen, Qiuying; Liu, Li; Zupan, Bojana; Toth, Miklos; Haynes, Robin; Huang, Xiaoping; Demirbas, Didem; Buccafusca, Roberto; Gross, Steven S.; Kanda, Vikram A.; Berry, Gerard T.

    2014-01-01

    Na+-coupled solute transport is crucial for the uptake of nutrients and metabolic precursors, such as myo-inositol, an important osmolyte and precursor for various cell signaling molecules. Here, we found that various solute transporters and potassium channel subunits formed complexes and reciprocally regulated each other in vitro and in vivo. Global metabolite profiling revealed that mice lacking KCNE2, a K+ channel β subunit, showed a reduction in the myo-inositol concentration in cerebrospinal fluid (CSF) but not in serum. Increased behavorial responsiveness to stress and seizure susceptibility in Kcne2−/− mice were alleviated by injections of myo-inositol. Suspecting a defect in myo-inositol transport, we found that KCNE2 and KCNQ1, a voltage-gated potassium channel α subunit, colocalized and coimmunoprecipitated with SMIT1, a Na+-coupled myo-inositol transporter, in the choroid plexus epithelium. Heterologous coexpression demonstrated that myo-inositol transport by SMIT1 was augmented by coexpression of KCNQ1 but inhibited by coexpression of both KCNQ1 and KCNE2, which form a constitutively active, heteromeric K+ channel. SMIT1 and the related transporter SMIT2 were also inhibited by a constitutively active mutant form of KCNQ1. The activity of KCNQ1 and KCNQ1-KCNE2 were augmented by SMIT1 and the glucose transporter SGLT1, but suppressed by SMIT2. Channel-transporter signaling complexes may be a widespread mechanism to facilitate solute transport and electrochemical crosstalk. PMID:24595108

  10. Down-regulation of UDP-glucose dehydrogenase affects glycosaminoglycans synthesis and motility in HCT-8 colorectal carcinoma cells

    SciTech Connect

    Wang, Tsung-Pao; Pan, Yun-Ru; Fu, Chien-Yu; Chang, Hwan-You

    2010-10-15

    UDP-glucose dehydrogenase (UGDH) catalyzes oxidation of UDP-glucose to yield UDP-glucuronic acid, a precursor of hyaluronic acid (HA) and other glycosaminoglycans (GAGs) in extracellular matrix. Although association of extracellular matrix with cell proliferation and migration has been well documented, the importance of UGDH in these behaviors is not clear. Using UGDH-specific small interference RNA to treat HCT-8 colorectal carcinoma cells, a decrease in both mRNA and protein levels of UGDH, as well as the cellular UDP-glucuronic acid and GAG production was observed. Treatment of HCT-8 cells with either UGDH-specific siRNA or HA synthesis inhibitor 4-methylumbelliferone effectively delayed cell aggregation into multicellular spheroids and impaired cell motility in both three-dimensional collagen gel and transwell migration assays. The reduction in cell aggregation and migration rates could be restored by addition of exogenous HA. These results indicate that UGDH can regulate cell motility through the production of GAG. The enzyme may be a potential target for therapeutic intervention of colorectal cancers.

  11. NG2 expression in microglial cells affects the expression of neurotrophic and proinflammatory factors by regulating FAK phosphorylation

    PubMed Central

    Zhu, Lie; Su, Qing; Jie, Xiang; Liu, Antang; Wang, Hui; He, Beiping; Jiang, Hua

    2016-01-01

    Neural/glial antigen 2 (NG2), a chondroitin sulfate proteoglycan, is significantly upregulated in a subset of glial cells in the facial motor nucleus (FMN) following CNS injury. NG2 is reported to promote the resulting inflammatory reaction, however, the mechanism by which NG2 mediates these effects is yet to be determined. In this study, we examined the changes in NG2 expressing microglial cells in the FMN in response to facial nerve axotomy (FNA) in mice. Our findings indicated that NG2 expression was progressively induced and upregulated specifically in the ipsilateral facial nucleus following FNA. To further investigate the effects of NG2 expression, in vivo studies in NG2-knockout mice and in vitro studies in rat microglial cells transfected with NG2 shRNAs were performed. Abolition of NG2 expression both in vitro and in vivo resulted in increased expression of neurotrophic factors (nerve growth factor and glial derived neurotrophic factor), decreased expression of inflammatory mediators (tumor necrosis factor-α and interleukin-1β) and decreased apoptosis in the ipsilateral facial nucleus in response to FNA. Furthermore, we demonstrated the role of FAK in these NG2-induced effects. Taken together, our findings suggest that NG2 expression mediates inflammatory reactions and neurodegeneration in microglial cells in response to CNS injury, potentially by regulating FAK phosphorylation. PMID:27306838

  12. Soil Tillage Management Affects Maize Grain Yield by Regulating Spatial Distribution Coordination of Roots, Soil Moisture and Nitrogen Status.

    PubMed

    Wang, Xinbing; Zhou, Baoyuan; Sun, Xuefang; Yue, Yang; Ma, Wei; Zhao, Ming

    2015-01-01

    The spatial distribution of the root system through the soil profile has an impact on moisture and nutrient uptake by plants, affecting growth and productivity. The spatial distribution of the roots, soil moisture, and fertility are affected by tillage practices. The combination of high soil density and the presence of a soil plow pan typically impede the growth of maize (Zea mays L.).We investigated the spatial distribution coordination of the root system, soil moisture, and N status in response to different soil tillage treatments (NT: no-tillage, RT: rotary-tillage, SS: subsoiling) and the subsequent impact on maize yield, and identify yield-increasing mechanisms and optimal soil tillage management practices. Field experiments were conducted on the Huang-Huai-Hai plain in China during 2011 and 2012. The SS and RT treatments significantly reduced soil bulk density in the top 0-20 cm layer of the soil profile, while SS significantly decreased soil bulk density in the 20-30 cm layer. Soil moisture in the 20-50 cm profile layer was significantly higher for the SS treatment compared to the RT and NT treatment. In the 0-20 cm topsoil layer, the NT treatment had higher soil moisture than the SS and RT treatments. Root length density of the SS treatment was significantly greater than density of the RT and NT treatments, as soil depth increased. Soil moisture was reduced in the soil profile where root concentration was high. SS had greater soil moisture depletion and a more concentration root system than RT and NT in deep soil. Our results suggest that the SS treatment improved the spatial distribution of root density, soil moisture and N states, thereby promoting the absorption of soil moisture and reducing N leaching via the root system in the 20-50 cm layer of the profile. Within the context of the SS treatment, a root architecture densely distributed deep into the soil profile, played a pivotal role in plants' ability to access nutrients and water. An optimal

  13. Soil Tillage Management Affects Maize Grain Yield by Regulating Spatial Distribution Coordination of Roots, Soil Moisture and Nitrogen Status

    PubMed Central

    Wang, Xinbing; Zhou, Baoyuan; Sun, Xuefang; Yue, Yang; Ma, Wei; Zhao, Ming

    2015-01-01

    The spatial distribution of the root system through the soil profile has an impact on moisture and nutrient uptake by plants, affecting growth and productivity. The spatial distribution of the roots, soil moisture, and fertility are affected by tillage practices. The combination of high soil density and the presence of a soil plow pan typically impede the growth of maize (Zea mays L.).We investigated the spatial distribution coordination of the root system, soil moisture, and N status in response to different soil tillage treatments (NT: no-tillage, RT: rotary-tillage, SS: subsoiling) and the subsequent impact on maize yield, and identify yield-increasing mechanisms and optimal soil tillage management practices. Field experiments were conducted on the Huang-Huai-Hai plain in China during 2011 and 2012. The SS and RT treatments significantly reduced soil bulk density in the top 0–20 cm layer of the soil profile, while SS significantly decreased soil bulk density in the 20–30 cm layer. Soil moisture in the 20–50 cm profile layer was significantly higher for the SS treatment compared to the RT and NT treatment. In the 0-20 cm topsoil layer, the NT treatment had higher soil moisture than the SS and RT treatments. Root length density of the SS treatment was significantly greater than density of the RT and NT treatments, as soil depth increased. Soil moisture was reduced in the soil profile where root concentration was high. SS had greater soil moisture depletion and a more concentration root system than RT and NT in deep soil. Our results suggest that the SS treatment improved the spatial distribution of root density, soil moisture and N states, thereby promoting the absorption of soil moisture and reducing N leaching via the root system in the 20–50 cm layer of the profile. Within the context of the SS treatment, a root architecture densely distributed deep into the soil profile, played a pivotal role in plants’ ability to access nutrients and water. An

  14. Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy

    PubMed Central

    McCarthy, Antonio Desmond; Cortizo, Ana María; Sedlinsky, Claudia

    2016-01-01

    Patients with long-term type 1 and type 2 diabetes mellitus (DM) can develop skeletal complications or “diabetic osteopathy”. These include osteopenia, osteoporosis and an increased incidence of low-stress fractures. In this context, it is important to evaluate whether current anti-diabetic treatments can secondarily affect bone metabolism. Adenosine monophosphate-activated protein kinase (AMPK) modulates multiple metabolic pathways and acts as a sensor of the cellular energy status; recent evidence suggests a critical role for AMPK in bone homeostasis. In addition, AMPK activation is believed to mediate most clinical effects of the insulin-sensitizer metformin. Over the past decade, several research groups have investigated the effects of metformin on bone, providing a considerable body of pre-clinical (in vitro, ex vivo and in vivo) as well as clinical evidence for an anabolic action of metformin on bone. However, two caveats should be kept in mind when considering metformin treatment for a patient with type 2 DM at risk for diabetic osteopathy. In the first place, metformin should probably not be considered an anti-osteoporotic drug; it is an insulin sensitizer with proven macrovascular benefits that can secondarily improve bone metabolism in the context of DM. Secondly, we are still awaiting the results of randomized placebo-controlled studies in humans that evaluate the effects of metformin on bone metabolism as a primary endpoint. PMID:27022443

  15. Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy.

    PubMed

    McCarthy, Antonio Desmond; Cortizo, Ana María; Sedlinsky, Claudia

    2016-03-25

    Patients with long-term type 1 and type 2 diabetes mellitus (DM) can develop skeletal complications or "diabetic osteopathy". These include osteopenia, osteoporosis and an increased incidence of low-stress fractures. In this context, it is important to evaluate whether current anti-diabetic treatments can secondarily affect bone metabolism. Adenosine monophosphate-activated protein kinase (AMPK) modulates multiple metabolic pathways and acts as a sensor of the cellular energy status; recent evidence suggests a critical role for AMPK in bone homeostasis. In addition, AMPK activation is believed to mediate most clinical effects of the insulin-sensitizer metformin. Over the past decade, several research groups have investigated the effects of metformin on bone, providing a considerable body of pre-clinical (in vitro, ex vivo and in vivo) as well as clinical evidence for an anabolic action of metformin on bone. However, two caveats should be kept in mind when considering metformin treatment for a patient with type 2 DM at risk for diabetic osteopathy. In the first place, metformin should probably not be considered an anti-osteoporotic drug; it is an insulin sensitizer with proven macrovascular benefits that can secondarily improve bone metabolism in the context of DM. Secondly, we are still awaiting the results of randomized placebo-controlled studies in humans that evaluate the effects of metformin on bone metabolism as a primary endpoint. PMID:27022443

  16. The Sensor Histidine Kinase RgfC Affects Group B Streptococcal Virulence Factor Expression Independent of Its Response Regulator RgfA

    PubMed Central

    Gendrin, Claire; Lembo, Annalisa; Whidbey, Christopher; Burnside, Kellie; Berry, Jessica; Ngo, Lisa; Banerjee, Anirban; Xue, Liang; Arrington, Justine; Doran, Kelly S.; Tao, W. Andy

    2015-01-01

    Group B streptococci (GBS; Streptococcus agalactiae) are beta-hemolytic, Gram-positive bacteria that are common asymptomatic colonizers of healthy adults. However, these opportunistic bacteria also cause invasive infections in human newborns and in certain adult populations. To adapt to the various environments encountered during its disease cycle, GBS encodes a number of two-component signaling systems. Previous studies have indicated that the TCS comprising the sensor histidine kinase RgfC and the response regulator RgfA mediate GBS binding to extracellular matrix components, such as fibrinogen. However, in certain GBS clinical isolates, a point mutation in rgfA results in premature truncation of the response regulator. The truncated RgfA protein lacks the C-terminal DNA binding domain necessary for promoter binding and gene regulation. Here, we show that deletion of rgfC in GBS strains lacking a functional RgfA increased systemic infection. Furthermore, infection with the rgfC mutant increased induction of proinflammatory signaling pathways in vivo. Phosphoproteomic analysis revealed that 19 phosphopeptides corresponding to 12 proteins were differentially phosphorylated at aspartate, cysteine, serine, threonine, or tyrosine residues in the rgfC mutant. This included aspartate phosphorylation of a tyrosine kinase, CpsD, and a transcriptional regulator. Consistent with this observation, microarray analysis of the rgfC mutant indicated that >200 genes showed altered expression compared to the isogenic wild-type strain and included transcriptional regulators, transporters, and genes previously associated with GBS pathogenesis. Our observations suggest that in the absence of RgfA, nonspecific RgfC signaling affects the expression of virulence factors and GBS pathogenesis. PMID:25561709

  17. The sensor histidine kinase RgfC affects group B streptococcal virulence factor expression independent of its response regulator RgfA.

    PubMed

    Gendrin, Claire; Lembo, Annalisa; Whidbey, Christopher; Burnside, Kellie; Berry, Jessica; Ngo, Lisa; Banerjee, Anirban; Xue, Liang; Arrington, Justine; Doran, Kelly S; Tao, W Andy; Rajagopal, Lakshmi

    2015-03-01

    Group B streptococci (GBS; Streptococcus agalactiae) are beta-hemolytic, Gram-positive bacteria that are common asymptomatic colonizers of healthy adults. However, these opportunistic bacteria also cause invasive infections in human newborns and in certain adult populations. To adapt to the various environments encountered during its disease cycle, GBS encodes a number of two-component signaling systems. Previous studies have indicated that the TCS comprising the sensor histidine kinase RgfC and the response regulator RgfA mediate GBS binding to extracellular matrix components, such as fibrinogen. However, in certain GBS clinical isolates, a point mutation in rgfA results in premature truncation of the response regulator. The truncated RgfA protein lacks the C-terminal DNA binding domain necessary for promoter binding and gene regulation. Here, we show that deletion of rgfC in GBS strains lacking a functional RgfA increased systemic infection. Furthermore, infection with the rgfC mutant increased induction of proinflammatory signaling pathways in vivo. Phosphoproteomic analysis revealed that 19 phosphopeptides corresponding to 12 proteins were differentially phosphorylated at aspartate, cysteine, serine, threonine, or tyrosine residues in the rgfC mutant. This included aspartate phosphorylation of a tyrosine kinase, CpsD, and a transcriptional regulator. Consistent with this observation, microarray analysis of the rgfC mutant indicated that >200 genes showed altered expression compared to the isogenic wild-type strain and included transcriptional regulators, transporters, and genes previously associated with GBS pathogenesis. Our observations suggest that in the absence of RgfA, nonspecific RgfC signaling affects the expression of virulence factors and GBS pathogenesis. PMID:25561709

  18. A Logistic Regression Mixture Model for Interval Mapping of Genetic Trait Loci Affecting Binary Phenotypes

    PubMed Central

    Deng, Weiping; Chen, Hanfeng; Li, Zhaohai

    2006-01-01

    Often in genetic research, presence or absence of a disease is affected by not only the trait locus genotypes but also some covariates. The finite logistic regression mixture models and the methods under the models are developed for detection of a binary trait locus (BTL) through an interval-mapping procedure. The maximum-likelihood estimates (MLEs) of the logistic regression parameters are asymptotically unbiased. The null asymptotic distributions of the likelihood-ratio test (LRT) statistics for detection of a BTL are found to be given by the supremum of a χ2-process. The limiting null distributions are free of the null model parameters and are determined explicitly through only four (backcross case) or nine (intercross case) independent standard normal random variables. Therefore a threshold for detecting a BTL in a flanking marker interval can be approximated easily by using a Monte Carlo method. It is pointed out that use of a threshold incorrectly determined by reading off a χ2-probability table can result in an excessive false BTL detection rate much more severely than many researchers might anticipate. Simulation results show that the BTL detection procedures based on the thresholds determined by the limiting distributions perform quite well when the sample sizes are moderately large. PMID:16272416

  19. An affective-cognitive processing model of post-traumatic growth.

    PubMed

    Joseph, Stephen; Murphy, David; Regel, Stephen

    2012-01-01

    A topic that has begun to attract interest from clinical psychologists and psychotherapists is post-traumatic growth. First, we provide a general overview of the field, setting out the historical development, main concepts, measurement issues and research findings. Second, we review evidence showing that the relationship between post-traumatic stress and post-traumatic growth is likely curvilinear. Third, a new affective-cognitive processing model of post-traumatic growth will be introduced in which post-traumatic stress is understood to be the engine of post-traumatic growth. Fourth, points of clinical intervention are described showing the ways in which therapists can facilitate post-traumatic growth. PMID:22610981

  20. Stress Management Affects Outcomes in the Pathophysiology of an Endometriosis Model

    PubMed Central

    Cruz, Myrella L.; Hernández, Siomara; Thompson, Kenira J.; Bayona, Manuel; Flores, Idhaliz

    2014-01-01

    We have previously shown detrimental effects of stress in an animal model of endometriosis. We now investigated whether the ability to control stress can affect disease parameters. Endometriosis was surgically induced in female Sprague-Dawley rats before exposing animals to a controllable (submerged platform) or uncontrollable (no platform) swim stress protocol. Corticosterone levels and fecal pellet numbers were measured as an indicator of stress. Uncontrollable stress increased the number and size of the endometriotic cysts. Rats receiving uncontrollable stress had higher anxiety than those exposed to controllable stress or no stress and higher corticosterone levels. Uncontrollable stressed rats had more colonic damage and uterine cell infiltration compared to no stress, while controllable stress rats showed less of an effect. Uncontrollable stress also increased both colonic and uterine motility. In summary, the level of stress controllability appears to modulate the behavior and pathophysiology of endometriosis and offers evidence for evaluating therapeutic interventions. PMID:25015902

  1. A systematic experimental investigation of significant parameters affecting model tire hydroplaning

    NASA Technical Reports Server (NTRS)

    Wray, G. A.; Ehrlich, I. R.

    1973-01-01

    The results of a comprehensive parametric study of model and small pneumatic tires operating on a wet surface are presented. Hydroplaning inception (spin down) and rolling restoration (spin up) are discussed. Conclusions indicate that hydroplaning inception occurs at a speed significantly higher than the rolling restoration speed. Hydroplaning speed increases considerably with tread depth, surface roughness and tire inflation pressure of footprint pressure, and only moderately with increased load. Water film thickness affects spin down speed only slightly. Spin down speed varies inversely as approximately the one-sixth power of film thickness. Empirical equations relating tire inflation pressure, normal load, tire diameter and water film thickness have been generated for various tire tread and surface configurations.

  2. Interplay of model ingredients affecting aggregate shape plasticity in diffusion-limited aggregation

    NASA Astrophysics Data System (ADS)

    Duarte-Neto, P.; Stošić, T.; Stošić, B.; Lessa, R.; Milošević, M. V.

    2014-07-01

    We analyze the combined effect of three ingredients of an aggregation model—surface tension, particle flow and particle source—representing typical characteristics of many aggregation growth processes in nature. Through extensive numerical experiments and for different underlying lattice structures we demonstrate that the location of incoming particles and their preferential direction of flow can significantly affect the resulting general shape of the aggregate, while the surface tension controls the surface roughness. Combining all three ingredients increases the aggregate shape plasticity, yielding a wider spectrum of shapes as compared to earlier works that analyzed these ingredients separately. Our results indicate that the considered combination of effects is fundamental for modeling the polymorphic growth of a wide variety of structures in confined geometries and/or in the presence of external fields, such as rocks, crystals, corals, and biominerals.

  3. Regulation of Intertidal Microphytobenthos Photosynthesis Over a Diel Emersion Period Is Strongly Affected by Diatom Migration Patterns

    PubMed Central

    Cartaxana, Paulo; Cruz, Sónia; Gameiro, Carla; Kühl, Michael

    2016-01-01

    Changes in biomass and photosynthesis of a diatom-dominated microphytobenthos (MPB) intertidal community were studied over a diel emersion period using a combination of O2 and scalar irradiance microprofiling, variable chlorophyll (Chl) fluorescence, and pigment analysis. The MPB biomass in the photic zone (0–0.5 mm) of the sediment exposed to low irradiance (150 μmol photons m-2 s-1) showed a >2-fold increase during the first hours of the emersion period, reaching >0.2 mg Chl a cm-3. Concentrations of Chl a started to decrease half-way through the emersion period, almost 2 h before tidal inundation. Similarly, O2 concentrations and volumetric gross photosynthesis in the photic zone increased during the first half of the emersion period and then decreased toward the timing of incoming tide/darkness. The results suggest that intertidal MPB community-level photosynthesis is mainly controlled by changes in the productive biomass of the photic zone determined by cell migration. A diel pattern in the photosynthesis vs. irradiance parameters α (photosynthetic efficiency at limiting irradiance) and ETRmax (photosynthetic capacity at saturating irradiance) was also observed, suggesting photoacclimation of MPB. Under high light exposure (2000 μmol photons m-2 s-1), lower α, ETRmax and sediment O2 concentrations were observed when cell migration was inhibited with the diatom motility inhibitor latrunculin A (Lat A), showing that migration is also used by MPB to maximize photosynthesis by reducing exposure to potentially photoinhibitory light levels. A higher de-epoxidation state in sediment treated with Lat A indicates that the involvement of the xanthophyll cycle in physiological photoprotection is more relevant in MPB when cells are inhibited from migrating. In the studied diatom-dominated MPB intertidal community, cell migration seems to be the key factor regulating photosynthesis over a diel emersion period and upon changes in light exposure. PMID:27375593

  4. Regulation of Intertidal Microphytobenthos Photosynthesis Over a Diel Emersion Period Is Strongly Affected by Diatom Migration Patterns.

    PubMed

    Cartaxana, Paulo; Cruz, Sónia; Gameiro, Carla; Kühl, Michael

    2016-01-01

    Changes in biomass and photosynthesis of a diatom-dominated microphytobenthos (MPB) intertidal community were studied over a diel emersion period using a combination of O2 and scalar irradiance microprofiling, variable chlorophyll (Chl) fluorescence, and pigment analysis. The MPB biomass in the photic zone (0-0.5 mm) of the sediment exposed to low irradiance (150 μmol photons m(-2) s(-1)) showed a >2-fold increase during the first hours of the emersion period, reaching >0.2 mg Chl a cm(-3). Concentrations of Chl a started to decrease half-way through the emersion period, almost 2 h before tidal inundation. Similarly, O2 concentrations and volumetric gross photosynthesis in the photic zone increased during the first half of the emersion period and then decreased toward the timing of incoming tide/darkness. The results suggest that intertidal MPB community-level photosynthesis is mainly controlled by changes in the productive biomass of the photic zone determined by cell migration. A diel pattern in the photosynthesis vs. irradiance parameters α (photosynthetic efficiency at limiting irradiance) and ETR max (photosynthetic capacity at saturating irradiance) was also observed, suggesting photoacclimation of MPB. Under high light exposure (2000 μmol photons m(-2) s(-1)), lower α, ETR max and sediment O2 concentrations were observed when cell migration was inhibited with the diatom motility inhibitor latrunculin A (Lat A), showing that migration is also used by MPB to maximize photosynthesis by reducing exposure to potentially photoinhibitory light levels. A higher de-epoxidation state in sediment treated with Lat A indicates that the involvement of the xanthophyll cycle in physiological photoprotection is more relevant in MPB when cells are inhibited from migrating. In the studied diatom-dominated MPB intertidal community, cell migration seems to be the key factor regulating photosynthesis over a diel emersion period and upon changes in light exposure. PMID

  5. The Social Regulation of Emotion: An Integrative, Cross-Disciplinary Model.

    PubMed

    Reeck, Crystal; Ames, Daniel R; Ochsner, Kevin N

    2016-01-01

    Research in emotion regulation has largely focused on how people manage their own emotions, but there is a growing recognition that the ways in which we regulate the emotions of others also are important. Drawing on work from diverse disciplines, we propose an integrative model of the psychological and neural processes supporting the social regulation of emotion. This organizing framework, the 'social regulatory cycle', specifies at multiple levels of description the act of regulating another person's emotions as well as the experience of being a target of regulation. The cycle describes the processing stages that lead regulators to attempt to change the emotions of a target person, the impact of regulation on the processes that generate emotions in the target, and the underlying neural systems. PMID:26564248

  6. Modeling and Testing of Unbalanced Loading and Voltage Regulation

    SciTech Connect

    Davis, M. W.; Broadwater, R.; Hambrick, J.

    2007-07-01

    This report covers work to (1) develop and validate distribution circuit models, (2) determine optimum distributed generator operating conditions, and (3) determine distributed generation penetration limits.

  7. On the regulator-insurer interaction in a structural model

    NASA Astrophysics Data System (ADS)

    Bernard, Carole; Chen, An

    2009-11-01

    In this paper, we provide a new insight to the previous work of Briys and de Varenne [E. Briys, F. de Varenne, Life insurance in a contingent claim framework: Pricing and regulatory implications, Geneva Papers on Risk and Insurance Theory 19 (1) (1994) 53-72], Grosen and Jørgensen [A. Grosen, P.L. Jørgensen, Life insurance liabilities at market value: An analysis of insolvency risk, bonus policy, and regulatory intervention rules in a barrier option framework, Journal of Risk and Insurance 69 (1) (2002) 63-91] and Chen and Suchanecki [A. Chen, M. Suchanecki, Default risk, bankruptcy procedures and the market value of life insurance liabilities, Insurance: Mathematics and Economics 40 (2007) 231-255]. We show that the particular risk management strategy followed by the insurance company can significantly change the risk exposure of the company, and that it should thus be taken into account by regulators. We first study how the regulator establishes regulation intervention levels in order to control for instance the default probability of the insurance company. This part of the analysis is based on a constant volatility. Given that the insurance company is informed of regulatory rules, we study how results can be significantly different when the insurance company follows a risk management strategy with non-constant volatilities. We thus highlight some limits of the prior literature and believe that the risk management strategy of the company should be taken into account in the estimation of the risk exposure as well as in that of the market value of liabilities.

  8. [Quantum processes in evolution of regulation of living system (mathematical modelling)].

    PubMed

    Menshutkin, V V; Natochin, Iu V

    2011-01-01

    We have developed an imitation model of the appearance of regulation of physiological functions of protocell at the initial stages of evolution of living system. It is based on suggestion of the appearance of signal function in spontaneously formed products of partial hydrolysis of the protocell polypeptides, based on which there appear the regulatory molecules--quanta of regulation. For construction of the model, the mathematical apparatus of final automats and of genetic algorithm is used. The model has demonstrated the positive role of involvement of regulatory peptides in the system of regulation of protocell functions to provide its viability under the changing envelopment conditions. PMID:21780648

  9. Does amniotic fluid volume affect fetofetal transfusion in monochorionic twin pregnancies? Modelling two possible mechanisms

    NASA Astrophysics Data System (ADS)

    Umur, Asli; van Gemert, Martin J. C.; Ross, Michael G.

    2002-06-01

    Clinical evidence suggests that increased amniotic fluid volume due to polyhydramnios increases placental vascular resistance. We have sought to model the possible effects of an increased amniotic fluid volume on the net fetofetal transfusion in monochorionic twin pregnancies. We wanted to compare these effects with the results of previous simulations, which aimed to explain why the twin-twin transfusion syndrome (TTTS) placentas more often include bidirectional arteriovenous (AV) rather than AV plus arterioarterial (AA) anastomoses. We extended our mathematical model of TTTS by simulating two different mechanisms that increase the placental vascular resistance as a consequence of polyhydramnios. First, there is an increase in the placental capillary resistance and hence in deep AV and opposite AV (denoted as VA) resistances due to polyhydramnios. Second, there is an increase in the resistance of chorionic veins due to polyhydramnios, assuming that these veins act as Starling resistors. We then simulated the effects of polyhydramnios on different placental anastomotic patterns. The results were as follows. In the first mechanism (polyhydramnios affects AV-VA resistances), an increased amniotic fluid volume hardly affected bidirectional AV, but slightly decreased fetofetal transfusion in AV plus AA anastomoses. However, for these effects to change the natural development of the pregnancy, polyhydramnios needed to persist for approximately 4 weeks, and by comparing the effects of polyhydramnios with the effects of amnioreduction, amnioreduction was more beneficial for normalizing the donor amniotic fluid volume. Therefore, these beneficial effects due to polyhydramnios have no practical clinical significance. In the second mechanism (Starling resistor for chorionic veins), polyhydramnios slightly increased fetofetal transfusion and hence slightly increased TTTS severity in bidirectional AV and AV plus VV, but did not affect AV plus AA anastomoses. In conclusion, we

  10. URC Fuzzy Modeling and Simulation of Gene Regulation

    SciTech Connect

    Sokhansanj, B A; Fitch, J P

    2001-05-01

    Recent technological advances in high-throughput data collection give biologists the ability to study increasingly complex systems. A new methodology is needed to develop and test biological models based on experimental observations and predict the effect of perturbations of the network (e.g. genetic engineering, pharmaceuticals, gene therapy). Diverse modeling approaches have been proposed, in two general categories: modeling a biological pathway as (a) a logical circuit or (b) a chemical reaction network. Boolean logic models can not represent necessary biological details. Chemical kinetics simulations require large numbers of parameters that are very difficult to accurately measure. Based on the way biologists have traditionally thought about systems, we propose that fuzzy logic is a natural language for modeling biology. The Union Rule Configuration (URC) avoids combinatorial explosion in the fuzzy rule base, allowing complex system models. We demonstrate the fuzzy modeling method on the commonly studied lac operon of E. coli. Our goal is to develop a modeling and simulation approach that can be understood and applied by biologists without the need for experts in other fields or ''black-box'' software.

  11. Up-regulation of glucocorticoid-regulated genes in a mouse model of Rett syndrome.

    PubMed

    Nuber, Ulrike A; Kriaucionis, Skirmantas; Roloff, Tim C; Guy, Jacky; Selfridge, Jim; Steinhoff, Christine; Schulz, Ralph; Lipkowitz, Bettina; Ropers, H Hilger; Holmes, Megan C; Bird, Adrian

    2005-08-01

    Rett syndrome (RTT) is a severe form of mental retardation, which is caused by spontaneous mutations in the X-linked gene MECP2. How the loss of MeCP2 function leads to RTT is currently unknown. Mice lacking the Mecp2 gene initially show normal postnatal development but later acquire neurological phenotypes, including heightened anxiety, that resemble RTT. The MECP2 gene encodes a methyl-CpG-binding protein that can act as a transcriptional repressor. Using cDNA microarrays, we found that Mecp2-null animals differentially express several genes that are induced during the stress response by glucocorticoids. Increased levels of mRNAs for serum glucocorticoid-inducible kinase 1 (Sgk) and FK506-binding protein 51 (Fkbp5) were observed before and after onset of neurological symptoms, but plasma glucocorticoid was not significantly elevated in Mecp2-null mice. MeCP2 is bound to the Fkbp5 and Sgk genes in brain and may function as a modulator of glucocorticoid-inducible gene expression. Given the known deleterious effect of glucocorticoid exposure on brain development, our data raise the possibility that disruption of MeCP2-dependent regulation of stress-responsive genes contributes to the symptoms of RTT. PMID:16002417

  12. Fractalkine Signaling Regulates the Inflammatory Response in an α-Synuclein Model of Parkinson Disease

    PubMed Central

    Thome, Aaron D.; Standaert, David G.; Harms, Ashley S.

    2015-01-01

    Background Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopamine neurons in the substantia nigra pars compacta (SNpc) and widespread aggregates of the protein alpha-synuclein (α-syn). Increasing evidence points to inflammation as a chief mediator; however, the role of α-syn in triggering and sustaining inflammation remains unclear. In models of Alzheimer’s disease (AD), multiple sclerosis (MS) and neurotoxin models of PD, the chemokine CX3CL1 (fractalkine) and its receptor (CX3CR1) have important roles in modulating neuroinflammation. Methods To examine the role of fractalkine signaling in α-syn-induced-neuroinflammation and neurodegeneration, we used an in vivo mouse model in which human α-syn is overexpressed by an adeno associated viral vector serotype 2 (AAV2) and in vitro phagocytosis and protein internalization assays with primary microglia treated with aggregated α-syn. Results We observed that loss of CX3CR1 expression led to a reduced inflammatory response, with reduced IgG deposition and expression of MHCII 4 weeks post-transduction. Six months post transduction, AAV2 mediated overexpression of α-syn leads to loss of dopaminergic neurons, and this loss was not exacerbated in animals with deletion of CX3CR1. To determine the mechanism by which CX3CR1affects inflammatory responses in α-syn-induced inflammation, phagocytosis was assessed using a fluorescent microsphere assay as well as by microglial uptake of aggregated α-syn. CX3CR1-/- microglia showed reduced uptake of fluorescent beads and aggregated α-syn. Conclusion Our results suggest that one mechanism by which CX3CR1-/- attenuates inflammation is at the level of phagocytosis of aggregated α-syn by microglia. These data implicate fractalkine signaling as a potential therapeutic target for regulating inflammatory response in α-syn models PD. PMID:26469270

  13. Parsimonious modelling of water and suspended sediment flux from nested catchments affected by selective tropical forestry.

    PubMed Central

    Chappell, N A; McKenna, P; Bidin, K; Douglas, I; Walsh, R P

    1999-01-01

    The ability to model the suspended sediment flux (SSflux) and associated water flow from terrain affected by selective logging is important to the establishment of credible measures to improve the ecological sustainability of forestry practices. Recent appreciation of the impact of parameter uncertainty on the statistical credibility of complex models with little internal state validation supports the use of more parsimonious approaches such as data-based mechanistic (DBM) modelling. The DBM approach combines physically based understanding with model structure identification based on transfer functions and objective statistical inference. Within this study, these approaches have been newly applied to rainfall-SSflux response. The dynamics of the sediment system, together with the rainfall-river flow system, were monitored at five nested contributory areas within a 44 ha headwater region in Malaysian Borneo. The data series analysed covered a whole year at a 5 min resolution, and were collected during a period some five to six years after selective timber harvesting had ceased. Physically based and statistical interpretation of these data was possible given the wealth of contemporary and past hydrogeomorphic data collected within the same region. The results indicated that parsimonious, three-parameter models of rainfall-river flow and rainfall-SSflux for the whole catchment describe 80 and 90% of the variance, respectively, and that parameter changes between scales could be explained in physically meaningful terms. Indeed, the modelling indicated some new conceptual descriptions of the river flow and sediment-generation systems. An extreme rainstorm having a 10-20 year return period was present within the data series and was shown to generate new mass movements along the forestry roads that had a differential impact on the monitored contributory areas. Critically, this spatially discrete behaviour was captured by the modelling and may indicate the potential use of

  14. RKP, a RING finger E3 ligase induced by BSCTV C4 protein, affects geminivirus infection by regulation of the plant cell cycle.

    PubMed

    Lai, Jianbin; Chen, Hao; Teng, Kunling; Zhao, Qingzhen; Zhang, Zhonghui; Li, Yin; Liang, Liming; Xia, Ran; Wu, Yaorong; Guo, Huishan; Xie, Qi

    2009-03-01

    The C4 protein from Curtovirus is known as a major symptom determinant, but the mode of action of the C4 protein remains unclear. To understand the mechanism of involvement of C4 protein in virus-plant interactions, we introduced the C4 gene from Beet severe curly top virus (BSCTV) into Arabidopsis under a conditional expression promoter; the resulting overexpression of BSCTV C4 led to abnormal host cell division. RKP, a RING finger protein, which is a homolog of the human cell cycle regulator KPC1, was discovered to be induced by BSCTV C4 protein. Mutation of RKP reduced the susceptibility to BSCTV in Arabidopsis and impaired BSCTV replication in plant cells. Callus formation is impaired in rkp mutants, indicating a role of RKP in the plant cell cycle. RKP was demonstrated to be a functional ubiquitin E3 ligase and is able to interact with cell-cycle inhibitor ICK/KRP proteins in vitro. Accumulation of the protein ICK2/KRP2 was found increased in the rkp mutant. The above results strengthen the possibility that RKP might regulate the degradation of ICK/KRP proteins. In addition, the protein level of ICK2/KRP2 was decreased upon BSCTV infection. Overexpression of ICK1/KRP1 in Arabidopsis could reduce the susceptibility to BSCTV. In conclusion, we found that RKP is induced by BSCTV C4 and may affect BSCTV infection by regulating the host cell cycle. PMID:19000158

  15. Expression-based GWAS identifies variants, gene interactions and key regulators affecting intramuscular fatty acid content and composition in porcine meat

    PubMed Central

    Puig-Oliveras, Anna; Revilla, Manuel; Castelló, Anna; Fernández, Ana I.; Folch, Josep M.; Ballester, Maria

    2016-01-01

    The aim of this work is to better understand the genetic mechanisms determining two complex traits affecting porcine meat quality: intramuscular fat (IMF) content and its fatty acid (FA) composition. With this purpose, expression Genome-Wide Association Study (eGWAS) of 45 lipid-related genes associated with meat quality traits in swine muscle (Longissimus dorsi) of 114 Iberian × Landrace backcross animals was performed. The eGWAS identified 241 SNPs associated with 11 genes: ACSM5, CROT, FABP3, FOS, HIF1AN, IGF2, MGLL, NCOA1, PIK3R1, PLA2G12A and PPARA. Three expression Quantitative Trait Loci (eQTLs) for IGF2, ACSM5 and MGLL were identified, showing cis-acting effects, whereas 16 eQTLs had trans regulatory effects. A polymorphism in the ACSM5 promoter region associated with its expression was identified. In addition, strong candidate genes regulating ACSM5, FOS, PPARA, PIK3R1, PLA2G12A and HIF1AN gene expression were also seen. Notably, the analysis highlighted the NR3C1 transcription factor as a strong candidate gene involved in the regulation of the 45 genes analysed. Finally, the IGF2, MGLL, MC2R, ARHGAP6, and NR3C1 genes were identified as potential regulators co-localizing within QTLs for fatness and growth traits in the IBMAP population. The results obtained increase our knowledge in the functional regulatory mechanisms involved in these complex traits.

  16. Human I-mfa domain proteins specifically interact with KSHV LANA and affect its regulation of Wnt signaling-dependent transcription

    SciTech Connect

    Kusano, Shuichi; Eizuru, Yoshito

    2010-06-04

    Kaposi's sarcoma-associated herpes virus (KSHV)-encoded latency-associated nuclear antigen (LANA) protein has been reported to interact with glycogen synthase kinase 3{beta} (GSK-3{beta}) and to negatively regulate its activity, leading to stimulation of GSK-3{beta}-dependent {beta}-catenin degradation. We show here that the I-mfa domain proteins, HIC (human I-mfa domain-containing protein) and I-mfa (inhibitor of MyoD family a), interacted in vivo with LANA through their C-terminal I-mfa domains. This interaction affected the intracellular localization of HIC, inhibited the LANA-dependent transactivation of a {beta}-catenin-regulated reporter construct, and decreased the level of the LANA.GSK-3{beta} complex. These data reveal for the first time that I-mfa domain proteins interact with LANA and negatively regulate LANA-mediated activation of Wnt signaling-dependent transcription by inhibiting the formation of the LANA.GSK-3{beta} complex.

  17. INTER-INDIVIDUAL VARIATION IN VERTEBRAL KINEMATICS AFFECTS PREDICTIONS OF NECK MUSCULOSKELETAL MODELS

    PubMed Central

    Nevins, Derek D.; Zheng, Liying; Vasavada, Anita N.

    2014-01-01

    Experimental studies have found significant variation in cervical intervertebral kinematics (IVK) among healthy subjects, but the effect of this variation on biomechanical properties, such as neck strength, has not been explored. The goal of this study was to quantify variation in model predictions of extension strength, flexion strength and gravitational demand (the ratio of gravitational load from the weight of the head to neck muscle extension strength), due to inter-subject variation in IVK. IVK were measured from sagittal radiographs of twenty-four subjects (14F, 10M) in five postures: maximal extension, mid-extension, neutral, mid-flexion, and maximal flexion. IVK were defined by the position (anterior-posterior and superior-inferior) of each cervical vertebra with respect to T1 and its angle with respect to horizontal, and fit with a cubic polynomial over the range of motion. The IVK of each subject were scaled and incorporated into musculoskeletal models to create models that were identical in muscle force- and moment-generating properties but had subject-specific kinematics. The effect of inter-subject variation in IVK was quantified using the coefficient of variation (COV), the ratio of the standard deviation to the mean. COV of extension strength ranged from 8 – 15% over the range of motion, but COV of flexion strength were 20 – 80%. Moreover, the COV of gravitational demand was 80 – 90%, because the gravitational demand is affected by head position as well as neck strength. These results indicate that including inter-individual variation in models is important for evaluating neck musculoskeletal biomechanical properties. PMID:25234351

  18. Does Mutual Interference Affect the Feeding Rate of Aphidophagous Coccinellids? A Modeling Perspective

    PubMed Central

    Papanikolaou, Nikos E.; Demiris, Nikos; Milonas, Panagiotis G.; Preston, Simon; Kypraios, Theodore

    2016-01-01

    Mutual interference involves direct interactions between individuals of the same species that may alter their foraging success. Larvae of aphidophagous coccinellids typically stay within a patch during their lifetime, displaying remarkable aggregation to their prey. Thus, as larvae are exposed to each other, frequent encounters may affect their foraging success. A study was initiated in order to determine the effect of mutual interference in the coccinellids’ feeding rate. One to four 4th larval instars of the fourteen-spotted ladybird beetle Propylea quatuordecimpunctata were exposed for 6 hours into plastic containers with different densities of the black bean aphid, Aphis fabae, on potted Vicia faba plants. The data were used to fit a purely prey-dependent Holling type II model and its alternatives which account for interference competition and have thus far been underutilized, i.e. the Beddington-DeAngelis, the Crowley-Martin and a modified Hassell-Varley model. The Crowley-Martin mechanistic model appeared to be slightly better among the competing models. The results showed that although the feeding rate became approximately independent of predator density at high prey density, some predator dependence in the coccinellid’s functional response was observed at the low prey—high predator density combination. It appears that at low prey densities, digestion breaks are negligible so that the predators do waste time interfering with each other, whereas at high prey densities time loss during digestion breaks may fully accommodate the cost of interference, so that the time cost may be negligible. PMID:26756980

  19. Free fatty acids chain length distribution affects the permeability of skin lipid model membranes.

    PubMed

    Uchiyama, Masayuki; Oguri, Masashi; Mojumdar, Enamul H; Gooris, Gert S; Bouwstra, Joke A

    2016-09-01

    The lipid matrix in the stratum corneum (SC) plays an important role in the barrier function of the skin. The main lipid classes in this lipid matrix are ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). The aim of this study was to determine whether a variation in CER subclass composition and chain length distribution of FFAs affect the permeability of this matrix. To examine this, we make use of lipid model membranes, referred to as stratum corneum substitute (SCS). We prepared SCS containing i) single CER subclass with either a single FFA or a mixture of FFAs and CHOL, or ii) a mixture of various CER subclasses with either a single FFA or a mixture of FFAs and CHOL. In vitro permeation studies were performed using ethyl-p-aminobenzoic acid (E-PABA) as a model drug. The flux of E-PABA across the SCS containing the mixture of FFAs was higher than that across the SCS containing a single FA with a chain length of 24 C atoms (FA C24), while the E-PABA flux was not effected by the CER composition. To select the underlying factors for the changes in permeability, the SCSs were examined by Fourier transform infrared spectroscopy (FTIR) and Small angle X-ray scattering (SAXS). All lipid models demonstrated a similar phase behavior. However, when focusing on the conformational ordering of the individual FFA chains, the shorter chain FFA (with a chain length of 16, 18 or 20 C atoms forming only 11m/m% of the total FFA level) had a higher conformational disordering, while the conformational ordering of the chains of the CER and FA C24 and FA C22 hardly did not change irrespective of the composition of the SCS. In conclusion, the conformational mobility of the short chain FFAs present only at low levels in the model SC lipid membranes has a great impact on the permeability of E-PABA. PMID:27287726

  20. The Development of Self-Regulation Skills through the Modeling and Structuring of Computer Programming.

    ERIC Educational Resources Information Center

    Armstrong, Anne-Marie

    1989-01-01

    Discusses self-regulation, learning to learn, and adaptive problem solving, and describes study of third, fifth, and eighth graders. The study investigated whether providing a model of self-regulating skills via teaching a computer to solve problems would increase the number tasks completed, and decrease the error and trial rate. (11 references)…