Isaacowitz, Derek M.; Choi, YoonSun
2012-01-01
Overview Previous studies on aging and attention to emotional information found that older adults may look away from negative stimuli to regulate their moods. However, it is an open question whether older adults’ tendency to look less at negative material comes at the expense of learning when negative information is also health-relevant. This study investigated how age-related changes in attention to negative but relevant information about skin cancer risk reduction influenced both subsequent health behavior and mood regulation. Methods Younger (18-25, n = 78) and older (60-92, n = 77) adults’ fixations toward videos containing negatively-valenced content and risk-reduction information about skin cancer were recorded with eye-tracking. Self-reported mood ratings were measured throughout. Behavioral outcome measures (e.g., answering knowledge questions about skin cancer, choosing a sunscreen, completing a skin self-exam) assessed participants’ learning of key health-relevant information, their interest in seeking additional information, and their engagement in protective behaviors. Results Older adults generally looked less at the negative video content, more rapidly regulated their moods, and learned fewer facts about skin cancer; yet, they engaged in a greater number of protective behaviors than did younger adults. Conclusions Older adults may demonstrate an efficient looking strategy that extracts important information without disrupting their moods, and they may compensate for less learning by engaging in a greater number of protective behaviors. Younger adults may be distracted by disruptions to their mood, constraining their engagement in protective behaviors. PMID:22149125
Isaacowitz, Derek M; Choi, Yoonsun
2012-09-01
Previous studies on aging and attention to emotional information found that older adults may look away from negative stimuli to regulate their moods. However, it is an open question whether older adults' tendency to look less at negative material comes at the expense of learning when negative information is also health-relevant. This study investigated how age-related changes in attention to negative but relevant information about skin cancer risk reduction influenced both subsequent health behavior and mood regulation. Younger (18-25 years of age, n = 78) and older (60-92 years of age, n = 77) adults' fixations toward videos containing negatively valenced content and risk-reduction information about skin cancer were recorded with eye-tracking. Self-reported mood ratings were measured throughout. Behavioral outcome measures (e.g., answering knowledge questions about skin cancer, choosing a sunscreen, completing a skin self-exam) assessed participants' learning of key health-relevant information, their interest in seeking additional information, and their engagement in protective behaviors. Older adults generally looked less at the negative video content, more rapidly regulated their moods, and learned fewer facts about skin cancer; yet, they engaged in a greater number of protective behaviors than did younger adults. Older adults may demonstrate an efficient looking strategy that extracts important information without disrupting their moods, and they may compensate for less learning by engaging in a greater number of protective behaviors. Younger adults may be distracted by disruptions to their mood, constraining their engagement in protective behaviors. PsycINFO Database Record (c) 2012 APA, all rights reserved.
Beyond CTLA-4 and PD-1, the Generation Z of Negative Checkpoint Regulators.
Le Mercier, Isabelle; Lines, J Louise; Noelle, Randolph J
2015-01-01
In the last two years, clinical trials with blocking antibodies to the negative checkpoint regulators CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. Multiple negative checkpoint regulators protect the host against autoimmune reactions but also restrict the ability of T cells to effectively attack tumors. Releasing these brakes has emerged as an exciting strategy for cancer treatment. Conversely, these pathways can be manipulated to achieve durable tolerance for treatment of autoimmune diseases and transplantation. In the future, treatment may involve combination therapy to target multiple cell types and stages of the adaptive immune responses. In this review, we describe the current knowledge on the recently discovered negative checkpoint regulators, future targets for immunotherapy.
Beyond CTLA-4 and PD-1, the Generation Z of Negative Checkpoint Regulators
Le Mercier, Isabelle; Lines, J. Louise; Noelle, Randolph J.
2015-01-01
In the last two years, clinical trials with blocking antibodies to the negative checkpoint regulators CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. Multiple negative checkpoint regulators protect the host against autoimmune reactions but also restrict the ability of T cells to effectively attack tumors. Releasing these brakes has emerged as an exciting strategy for cancer treatment. Conversely, these pathways can be manipulated to achieve durable tolerance for treatment of autoimmune diseases and transplantation. In the future, treatment may involve combination therapy to target multiple cell types and stages of the adaptive immune responses. In this review, we describe the current knowledge on the recently discovered negative checkpoint regulators, future targets for immunotherapy. PMID:26347741
Shao, ZhiHui; Deng, WanXin; Li, ShiYuan; He, JuanMei; Ren, ShuangXi; Huang, WeiRen; Lu, YinHua; Zhao, GuoPing
2015-01-01
ABSTRACT Ectoine and hydroxyectoine are excellent compatible solutes for bacteria to deal with environmental osmotic stress and temperature damages. The biosynthesis cluster of ectoine and hydroxyectoine is widespread among microorganisms, and its expression is activated by high salinity and temperature changes. So far, little is known about the mechanism of the regulation of the transcription of ect genes and only two MarR family regulators (EctR1 in methylobacteria and the EctR1-related regulator CosR in Vibrio cholerae) have been found to negatively regulate the expression of ect genes. Here, we characterize GlnR, the global regulator for nitrogen metabolism in actinomycetes, as a negative regulator for the transcription of ectoine/hydroxyectoine biosynthetic genes (ect operon) in Streptomyces coelicolor. The physiological role of this transcriptional repression by GlnR is proposed to protect the intracellular glutamate pool, which acts as a key nitrogen donor for both the nitrogen metabolism and the ectoine/hydroxyectoine biosynthesis. IMPORTANCE High salinity is deleterious, and cells must evolve sophisticated mechanisms to cope with this osmotic stress. Although production of ectoine and hydroxyectoine is one of the most frequently adopted strategies, the in-depth mechanism of regulation of their biosynthesis is less understood. So far, only two MarR family negative regulators, EctR1 and CosR, have been identified in methylobacteria and Vibrio, respectively. Here, our work demonstrates that GlnR, the global regulator for nitrogen metabolism, is a negative transcriptional regulator for ect genes in Streptomyces coelicolor. Moreover, a close relationship is found between nitrogen metabolism and osmotic resistance, and GlnR-mediated regulation of ect transcription is proposed to protect the intracellular glutamate pool. Meanwhile, the work reveals the multiple roles of GlnR in bacterial physiology. PMID:26170409
Can Better Emotion Regulation Protect against Suicidality in Traumatized Homeless Youth?
Barr, Nicholas; Fulginiti, Anthony; Rhoades, Harmony; Rice, Eric
2017-07-03
A substantial majority of homeless youth and young adults (HYA) experience abuse prior to and during homelessness. HYA also have high rates of posttraumatic stress disorder (PTSD) and suicidal behavior. This study investigated relationships between traumatic experiences, PTSD symptoms, substance use, and the protective effects of emotion regulation on outcome variables suicidal ideation and suicide attempts. Data were drawn from a sample of 398 HYA interviewed at 3 drop-in centers in Los Angeles County. A bivariate logistic regression modeling strategy was employed to examine relationships among demographic characteristics and dependent and independent variables. Trauma prior to homelessness and trauma prior to and after homelessness were positively associated with suicidal ideation, whereas emotional awareness and control demonstrated negative associations. PTSD symptoms were positively associated with suicide attempts, whereas emotional awareness and control demonstrated negative associations. Better emotion regulation is associated with reduced odds of suicidal ideation and attempts in HYA and may protect against effects of traumatic experiences. Interventions targeting emotion regulation skills in HYA to reduce suicidality associated with traumatic experiences merit additional investigation.
Florio, Francesca; Ferri, Cinzia; Scapin, Cristina; Feltri, M Laura; Wrabetz, Lawrence; D'Antonio, Maurizio
2018-05-02
Schwann cell differentiation and myelination in the PNS are the result of fine-tuning of positive and negative transcriptional regulators. As myelination starts, negative regulators are downregulated, whereas positive ones are upregulated. Fully differentiated Schwann cells maintain an extraordinary plasticity and can transdifferentiate into "repair" Schwann cells after nerve injury. Reactivation of negative regulators of myelination is essential to generate repair Schwann cells. Negative regulators have also been implicated in demyelinating neuropathies, although their role in disease remains elusive. Here, we used a mouse model of Charcot-Marie-Tooth neuropathy type 1B (CMT1B), the P0S63del mouse characterized by ER stress and the activation of the unfolded protein response, to show that adult Schwann cells are in a partial differentiation state because they overexpress transcription factors that are normally expressed only before myelination. We provide evidence that two of these factors, Sox2 and Id2, act as negative regulators of myelination in vivo However, their sustained expression in neuropathy is protective because ablation of Sox2 or/and Id2 from S63del mice of both sexes results in worsening of the dysmyelinating phenotype. This is accompanied by increased levels of mutant P0 expression and exacerbation of ER stress, suggesting that limited differentiation may represent a novel adaptive mechanism through which Schwann cells counter the toxic effect of a mutant terminal differentiation protein. SIGNIFICANCE STATEMENT In many neuropathies, Schwann cells express high levels of early differentiation genes, but the significance of these altered expression remained unclear. Because many of these factors may act as negative regulators of myelination, it was suggested that their misexpression could contribute to dysmyelination. Here, we show that the transcription factors Sox2 and Id2 act as negative regulators of myelination in vivo , but that their sustained expression in Charcot-Marie-Tooth type 1B (CMT1B) represents an adaptive response activated by the Schwann cells to reduce mutant protein toxicity and prevent demyelination. Copyright © 2018 the authors 0270-6474/18/384275-14$15.00/0.
Dunsmore, Julie C.; Booker, Jordan A.; Ollendick, Thomas H.
2012-01-01
We assessed linkages of mothers’ emotion coaching and children’s emotion regulation and emotion lability/negativity with children’s adjustment in 72 mother-child dyads seeking treatment for Oppositional Defiant Disorder (ODD). Dyads completed questionnaires and discussed emotion-related family events. Maternal emotion coaching was associated with children’s emotion regulation, which in turn was related to higher mother-reported adaptive skills, higher child-reported internalizing symptoms, and lower child-reported adjustment. When children were high in emotion lability/negativity, mothers’ emotion coaching was associated with lower mother and child reports of externalizing behavior. Results suggest the role of emotion regulation and emotion lability in child awareness of socio-emotional problems and support the potential of maternal emotion coaching as a protective factor for children with ODD, especially for those high in emotion lability. PMID:24187441
D'Lima, Gabrielle Maria; Pearson, Matthew R; Kelley, Michelle L
2012-06-01
This study examined protective behavioral strategies (PBS) as a potential mediator and moderator of the relationship between self-regulation and alcohol-related consequences. Participants were 249 first-year undergraduate men and women. The use of PBS partially mediated the relationship between self-regulation and alcohol-related problems (i.e., supporting the "self-control equals drinking control" hypothesis). However, use of PBS appeared more important for those with poorer self-regulation abilities (supporting the "PBS protect the impaired" hypothesis). Because both mediation and moderation were supported, a moderated mediation model was tested. The moderated mediation model demonstrated that the negative relationship between self-regulation and alcohol-related consequences could be explained by use of PBS for individuals with poor-to-average self-regulation but not for individuals with above-average, self-regulation abilities. Implications of the study's findings are discussed.
Shao, ZhiHui; Deng, WanXin; Li, ShiYuan; He, JuanMei; Ren, ShuangXi; Huang, WeiRen; Lu, YinHua; Zhao, GuoPing; Cai, ZhiMing; Wang, Jin
2015-10-01
Ectoine and hydroxyectoine are excellent compatible solutes for bacteria to deal with environmental osmotic stress and temperature damages. The biosynthesis cluster of ectoine and hydroxyectoine is widespread among microorganisms, and its expression is activated by high salinity and temperature changes. So far, little is known about the mechanism of the regulation of the transcription of ect genes and only two MarR family regulators (EctR1 in methylobacteria and the EctR1-related regulator CosR in Vibrio cholerae) have been found to negatively regulate the expression of ect genes. Here, we characterize GlnR, the global regulator for nitrogen metabolism in actinomycetes, as a negative regulator for the transcription of ectoine/hydroxyectoine biosynthetic genes (ect operon) in Streptomyces coelicolor. The physiological role of this transcriptional repression by GlnR is proposed to protect the intracellular glutamate pool, which acts as a key nitrogen donor for both the nitrogen metabolism and the ectoine/hydroxyectoine biosynthesis. High salinity is deleterious, and cells must evolve sophisticated mechanisms to cope with this osmotic stress. Although production of ectoine and hydroxyectoine is one of the most frequently adopted strategies, the in-depth mechanism of regulation of their biosynthesis is less understood. So far, only two MarR family negative regulators, EctR1 and CosR, have been identified in methylobacteria and Vibrio, respectively. Here, our work demonstrates that GlnR, the global regulator for nitrogen metabolism, is a negative transcriptional regulator for ect genes in Streptomyces coelicolor. Moreover, a close relationship is found between nitrogen metabolism and osmotic resistance, and GlnR-mediated regulation of ect transcription is proposed to protect the intracellular glutamate pool. Meanwhile, the work reveals the multiple roles of GlnR in bacterial physiology. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Dvorak, Robert D.; Pearson, Matthew R.; Neighbors, Clayton; Martens, Matthew P.
2015-01-01
OBJECTIVE Heavy alcohol use remains a consistent public health concern on college campuses. The current pilot study used Deviance Regulation Theory (DRT) to modify Protective Behavioral Strategies (PBS) among college student drinkers to reduce alcohol use and alcohol-related consequences. METHODS The sample was comprised of current college student drinkers (n = 76; 53.95% female) ranging in age from 18-24 (M = 19.29, SD = 1.42). Participants were randomly assigned to receive a positive or negative framed message. They then reported on use of alcohol protective behavioral strategies (via the Protective Behavioral Strategies Scale), alcohol consumption (via the Modified Daily Drinking Questionnaire), and alcohol-related consequences (via the Young Adults Alcohol Consequences Questionnaire) each week for six weeks. RESULTS AND CONCLUSIONS Among drinkers with low PBS use norms, a positively, versus a negatively, framed message resulted in increased PBS use and consequently less alcohol consumption and fewer alcohol-related consequences. Among drinkers with high PBS use norms, a negatively, versus positively, framed message resulted in increased PBS use and consequently lower alcohol consumption and fewer alcohol-related consequences. However, these effects were only relevant among those who strongly believed the DRT frame. Findings suggest assigning drinkers to frames based on perceived PBS use norms and increasing belief in the frame may be one approach to increasing responsible drinking patterns among college students. Furthermore, the current data suggests important boundary conditions for norm-based interventions. PUBLIC HEALTH RELEVANCE This study of college student drinkers who received either a positive or negative framed message about reducing their drinking found that a Deviance Regulation intervention might be effective at increasing responsible alcohol use, but only among students with a high acceptance of the intervention materials. PMID:25798727
Wei, Wei; Li, Xiaoming; Tu, Xiaoming; Zhao, Junfeng; Zhao, Guoxiang
2016-01-01
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.
TRIM29 Negatively Regulates the Type I IFN Production in Response to RNA Virus.
Xing, Junji; Zhang, Ao; Minze, Laurie J; Li, Xian Chang; Zhang, Zhiqiang
2018-05-16
The innate immunity is critically important in protection against virus infections, and in the case of RNA viral infections, the signaling mechanisms that initiate robust protective innate immunity without triggering autoimmune inflammation remain incompletely defined. In this study, we found the E3 ligase TRIM29 was specifically expressed in poly I:C-stimulated human myeloid dendritic cells. The induced TRIM29 played a negative role in type I IFN production in response to poly I:C or dsRNA virus reovirus infection. Importantly, the challenge of wild-type mice with reovirus led to lethal infection. In contrast, deletion of TRIM29 protected the mice from this developing lethality. Additionally, TRIM29 -/- mice have lower titers of reovirus in the heart, intestine, spleen, liver, and brain because of elevated production of type I IFN. Mechanistically, TRIM29 was shown to interact with MAVS and subsequently induce its K11-linked ubiquitination and degradation. Taken together, TRIM29 regulates negatively the host innate immune response to RNA virus, which could be employed by RNA viruses for viral pathogenesis. Copyright © 2018 by The American Association of Immunologists, Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Qiang, Weiguang; Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou; Wu, Qinqin
Highlights: • Down-regulation of TPP1 shortened telomere length in telomerase-negative cells. • Down-regulation of TPP1 induced cell apoptosis in telomerase-negative cells. • Down-regulation of TPP1 increased radiosensitivity in telomerase-negative cells. - Abstract: Mammalian telomeres are protected by the shelterin complex that contains the six core proteins POT1, TPP1, TIN2, TRF1, TRF2 and RAP1. TPP1, formerly known as TINT1, PTOP, and PIP1, is a key factor that regulates telomerase recruitment and activity. In addition to this, TPP1 is required to mediate the shelterin assembly and stabilize telomere. Previous work has found that TPP1 expression was elevated in radioresistant cells and thatmore » overexpression of TPP1 led to radioresistance and telomere lengthening in telomerase-positive cells. However, the exact effects and mechanism of TPP1 on radiosensitivity are yet to be precisely defined in the ALT cells. Here we report on the phenotypes of the conditional deletion of TPP1 from the human osteosarcoma U2OS cells using ALT pathway to extend the telomeres.TPP1 deletion resulted in telomere shortening, increased apoptosis and radiation sensitivity enhancement. Together, our findings show that TPP1 plays a vital role in telomere maintenance and protection and establish an intimate relationship between TPP1, telomere and cellular response to ionizing radiation, but likely has the specific mechanism yet to be defined.« less
ERIC Educational Resources Information Center
Dunsmore, Julie C.; Booker, Jordan A.; Ollendick, Thomas H.
2013-01-01
We assessed linkages of mothers' emotion coaching and children's emotion regulation and emotion lability/negativity with children's adjustment in 72 mother-child dyads seeking treatment for oppositional defiant disorder (ODD). Dyads completed the questionnaires and discussed emotion-related family events. Maternal emotion coaching was associated…
The effect of the social regulation of emotion on emotional long-term memory.
Flores, Luis E; Berenbaum, Howard
2017-04-01
Memories for emotional events tend to be stronger than for neutral events, and weakening negative memories can be helpful to promote well-being. The present study examined whether the social regulation of emotion (in the form of handholding) altered the strength of emotional long-term memory. A sample of 219 undergraduate students viewed sets of negative, neutral, and positive images. Each participant held a stress ball while viewing half of the images and held someone's hand while viewing the other half. Participants returned 1 week later to complete a recognition task. Performance on the recognition task demonstrated that participants had lower memory accuracy for negative but not for positive pictures that were shown while they were holding someone's hand compared with when they were holding a stress ball. Although handholding altered the strength of negative emotional long-term memory, it did not down-regulate negative affective response as measured by self-report or facial expressivity. The present findings provide evidence that the social regulation of emotion can help weaken memory for negative information. Given the role of strong negative memories in different forms of psychopathology (e.g., depression, posttraumatic stress disorder), these findings may help better understand how close relationships protect against psychopathology. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Environmental Protection: Can We Afford It
1993-04-01
economic stability is weakening as businesses close down, cut back, or relocate. This paper looks at how much the U.S. is spending on environmental protection and considers the benefits derived from the dollars invested, discusses some of the impacts resulting from strict environmental regulation, and offers some options to alleviate the negative consequences of current U.S. environmental
Risk behaviours among early adolescents: risk and protective factors.
Wang, Ruey-Hsia; Hsu, Hsiu-Yueh; Lin, Shu-Yuan; Cheng, Chung-Ping; Lee, Shu-Li
2010-02-01
This paper is a report of a study conducted to examine the influence of risk/protective factors on risk behaviours of early adolescents and whether protective factors moderate their impact. An understanding of how risk and protective factors operate to influence risk behaviours of early adolescents will better prepare nurses to perform interventions appropriately to reduce risk behaviours of early adolescents. A cross-sectional study was carried out, based on a sample of public junior high schools (from 7th to 9th grades) in one city and one county in Taiwan. An anonymous questionnaire designed to measure five risk factors, six protective factors and risk behaviours was administered from October 2006 to March 2007. Data from 878 students were used for the present analysis. Pearson's correlations, anova with random effect models, and generalized linear models were used to analyse the statistically significant explanatory variables for risk behaviours. Gender, perceived father's risk behaviour, perceived mother's risk behaviour, health self-efficacy, interaction of health self-efficacy and perceived peers' risk behaviour, and interaction of emotional regulation and perceived peers' risk behaviour were statistically significant explanatory variables of risk behaviours. Health self-efficacy and emotional regulation moderated the negative effects of peers' perceived risk behaviour on risk behaviours. All protective factors were negative statistically correlated with risk behaviours, and all risk factors positively statistically correlated with risk behaviours. Male adolescents should be considered an at-risk group for risk behaviour intervention. Nurses could provide early adolescents with training regarding health self-efficacy improvement, self-esteem enhancement, emotional regulation skills to reduce their risk behaviours.
Overall, Nickola C; Sibley, Chris G
2009-08-01
This diary study examined situational dependence within daily interactions with family members and close friends over a 2-week period. Experiencing low personal control (high situational dependence) when interacting with family members and friends was associated with lower perceived regard and intimacy. Participants generally regulated felt dependence by derogating and withdrawing from their interaction partner (self-protective dependence regulation) and exhibiting lower levels of positive behavior, such as expressing thoughts and feelings or trying to improve the interaction (relationship-promotive dependence regulation). Furthermore, higher rejection sensitivity (but not low self-esteem) was associated with more negative evaluations of perceived regard and intimacy, greater self-protective dependence regulation, and lower relationship-promotive dependence regulation within low control interactions. These results identify dependence as a key element of rejection risk contexts and support the situation-specific nature of rejection sensitivity.
Negative Regulation of Type 2 Immunity
de Kouchkovsky, Dimitri A.; Ghosh, Sourav; Rothlin, Carla V.
2017-01-01
Type 2 immunity encompasses the mechanisms through which the immune system responds to helminths and an array of environmental substances such as allergens. In the developing world, billions of individuals are chronically infected with endemic parasitic helminths. In comparison, in the industrialized world, millions of individuals suffer from dysregulated type 2 immunity, referred to clinically as atopic diseases including asthma, allergic rhinitis and atopic dermatitis. Thus, type 2 immunity must be carefully regulated to mount protective host response yet avoid inappropriate activation and immunopathology. In this review, we describe the keys players and connections at play in type 2 responses and focus on the emerging mechanisms involved in the negative regulation of type 2 immunity. PMID:28082101
Wei, Wei; Li, Xiaoming; Harrison, Sayward; Zhao, Junfeng; Zhao, Guoxiang
2016-03-01
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 their treatments with this population.
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 their treatments with this population. PMID:27392011
Diab, Marwan; Peltonen, Kirsi; Qouta, Samir R; Palosaari, Esa; Punamäki, Raija-Leena
2017-04-19
Effective emotion regulation (ER) is expected to protect mental health in traumatic stress. We first analysed the protective (moderator) function of different ER strategies and the associations between ER and mental health. Second, we tested gender differences in the protective function of ER and the associations between ER strategies and mental health. Participants were 482 Palestinian children (girls 49.4%; 10-13 years, M = 11.29, SD = .68) whose ER was assessed by the Emotion Regulation Questionnaire and mental health by post-traumatic stress (Children's Impact Event Scale), depressive, and psychological distress (Strengths and Difficulties Questionnaire) symptoms, and by psychosocial well-being (Mental Health Continuum-Short Form). War trauma involved 42 events. Results showed, first, that none of the ER strategies could protect a child's mental health from negative impact of war trauma, but self-focused ER was associated with low depressive symptoms, and other-facilitated ER with high psychological well-being. However, controlling of emotions formed a comprehensive risk for children's mental health. Second, gender differences were found in the protective role of ER, as self-focused and distractive ER formed a vulnerability among boys. The results are discussed in the context of emotional and regulative demands of war and life-threat. © 2017 International Union of Psychological Science.
Panickar, Kiran S; Nonner, Doris; White, Michael G; Barrett, John N
2008-09-01
Activation of cyclin dependent kinases (Cdks) contributes to neuronal death following ischemia. We used oxygen-glucose deprivation (OGD) in septal neuronal cultures to test for possible roles of cell cycle proteins in neuronal survival. Increased cdc2-immunoreactive neurons were observed at 24 h after the end of 5 h OGD. Green fluorescent protein (GFP) or GFP along with a wild type or dominant negative form of the retinoblastoma protein (Rb), or cyclin-dependent kinase5 (Cdk5), were overexpressed using plasmid constructs. Following OGD, when compared to controls, neurons expressing both GFP and dominant negative Rb, RbDeltaK11, showed significantly less damage using microscopy imaging. Overexpression of Rb-wt did not affect survival. Surprisingly, overexpression of Cdk5-wild type significantly protected neurons from process disintegration but Cdk5T33, a dominant negative Cdk5, gave little or no protection. Thus phosphorylation of the cell cycle regulator, Rb, contributes to death in OGD in septal neurons but Cdk5 can have a protective role.
The Strong African American Families Program: translating research into prevention programming.
Brody, Gene H; Murry, Velma McBride; Gerrard, Meg; Gibbons, Frederick X; Molgaard, Virginia; McNair, Lily; Brown, Anita C; Wills, Thomas A; Spoth, Richard L; Luo, Zupei; Chen, Yi-Fu; Neubaum-Carlan, Eileen
2004-01-01
A randomized prevention trial contrasted families who took part in the Strong African American Families Program (SAAF), a preventive intervention for rural African American mothers and their 11-year-olds, with control families. SAAF is based on a contextual model positing that regulated, communicative parenting causes changes in factors protecting youths from early alcohol use and sexual activity. Parenting variables included involvement-vigilance, racial socialization, communication about sex, and clear expectations for alcohol use. Youth protective factors included negative attitudes about early alcohol use and sexual activity, negative images of drinking youths, resistance efficacy, a goal-directed future orientation, and acceptance of parental influence. Intervention-induced changes in parenting mediated the effect of intervention group influences on changes in protective factors over a 7-month period.
Ding, NanXiang; Yang, JieMin; Liu, YingYing; Yuan, JiaJin
2015-08-01
Previous studies indicate that emotion regulation may occur unconsciously, without the cost of cognitive effort, while conscious acceptance may enhance negative experiences despite having potential long-term health benefits. Thus, it is important to overcome this weakness to boost the efficacy of the acceptance strategy in negative emotion regulation. As unconscious regulation occurs with little cost of cognitive resources, the current study hypothesizes that unconscious acceptance regulates the emotional consequence of negative events more effectively than does conscious acceptance. Subjects were randomly assigned to conscious acceptance, unconscious acceptance and no-regulation conditions. A frustrating arithmetic task was used to induce negative emotion. Emotional experiences were assessed on the Positive Affect and Negative Affect Scale while emotion- related physiological activation was assessed by heart-rate reactivity. Results showed that conscious acceptance had a significant negative affective consequence, which was absent during unconscious acceptance. That is, unconscious acceptance was linked with little reduction of positive affect during the experience of frustration, while this reduction was prominent in the control and conscious acceptance groups. Instructed, conscious acceptance resulted in a greater reduction of positive affect than found for the control group. In addition, both conscious and unconscious acceptance strategies significantly decreased emotion-related heart-rate activity (to a similar extent) in comparison with the control condition. Moreover, heart-rate reactivity was positively correlated with negative affect and negatively correlated with positive affect during the frustration phase relative to the baseline phase, in both the control and unconscious acceptance groups. Thus, unconscious acceptance not only reduces emotion-related physiological activity but also better protects mood stability compared with conscious acceptance. This suggests that the clinical practice of acceptance therapy may need to consider using the unconscious priming of an accepting attitude, instead of intentionally instructing people to implement such a strategy, to boost the efficacy of acceptance in emotion regulation.
Use of Signs as a Protective Measure for Cultural Resources Sites
1993-04-01
3-4) succinctly defines prosocial behavior in the following manner: ... voluntary helping behavior that is not motivated by the expectation of...material rewards, or the fear of probable punishment for not helping . Obeying protective regulations can be a form of prosocial behavior in that such...ignored. In general, psychological research on prosocial behavior shows that helping actions can be induced by making people aware of the negative
Sommet, Nicolas; Darnon, Céline; Mugny, Gabriel; Quiamzade, Alain; Pulfrey, Caroline; Dompnier, Benoît; Butera, Fabrizio
2014-03-01
Socio-cognitive conflict has been defined as a situation of confrontation with a disagreeing other. Previous research suggests that individuals can regulate conflict in a relational way, namely by focusing on social comparison between relative levels of competences. Relational conflict regulation has been described as yielding particularly negative effects on social interactions and learning, but has been understudied. The present research addresses the question of the origin of relational conflict regulation by introducing a fundamental distinction between two types of regulation, one based on the affirmation of one's own point of view and the invalidation of the other's (i.e., 'competitive' regulation), the other corresponding to the protection of self-competence via compliance (i.e., 'protective' regulation). Three studies show that these modes of relational conflict regulation result from the endorsement of distinct performance goals, respectively, performance-approach goals (trying to outperform others) and performance-avoidance goals (avoiding performing more poorly than others). Theoretical implications for the literature on both conflict regulation and achievement goals are discussed. © 2012 The British Psychological Society.
The social regulation of emotion and updating negative contents of working memory.
Flores, Luis E; Berenbaum, Howard
2017-06-01
The social regulation of emotion reduces negative affect and may also help remove negative contents from working memory. The present studies investigated whether the social regulation of emotion (in the form of handholding) altered the ability to update negative contents from working memory and whether a person's level of desired emotional closeness moderated this effect. In each of 2 studies, an unselected sample of undergraduate students completed an emotional working memory task that measured the ability to remove irrelevant information from working memory and a self-report questionnaire measuring their level of desired emotional closeness. In Study 1 (N = 109), the task consisted only of negative images, and each participant performed half of the task while holding someone's hand and the other half while not holding someone's hand. Study 2 (N = 195) included a few changes (e.g., using both negative and neutral images, altering the control condition to consist of holding a stress ball, using a between-participants design, measuring comfort with handholding) to address a few potential alternative explanations. Overall, there appeared to be a better ability to update negative contents of working memory in the handholding condition of each study than the control condition among people with high desired emotional closeness but not among people with low desired emotional closeness. The present findings provide evidence that the social regulation of emotion can facilitate the removal of irrelevant negative contents of working memory. This process may be one way in which supportive relationships protect against psychological distress. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
PKC{eta} is a negative regulator of AKT inhibiting the IGF-I induced proliferation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shahaf, Galit; Rotem-Dai, Noa; Koifman, Gabriela
2012-04-15
The PI3K-AKT pathway is frequently activated in human cancers, including breast cancer, and its activation appears to be critical for tumor maintenance. Some malignant cells are dependent on activated AKT for their survival; tumors exhibiting elevated AKT activity show sensitivity to its inhibition, providing an Achilles heel for their treatment. Here we show that the PKC{eta} isoform is a negative regulator of the AKT signaling pathway. The IGF-I induced phosphorylation on Ser473 of AKT was inhibited by the PKC{eta}-induced expression in MCF-7 breast adenocarcinoma cancer cells. This was further confirmed in shRNA PKC{eta}-knocked-down MCF-7 cells, demonstrating elevated phosphorylation on AKTmore » Ser473. While PKC{eta} exhibited negative regulation on AKT phosphorylation it did not alter the IGF-I induced ERK phosphorylation. However, it enhanced ERK phosphorylation when stimulated by PDGF. Moreover, its effects on IGF-I/AKT and PDGF/ERK pathways were in correlation with cell proliferation. We further show that both PKC{eta} and IGF-I confer protection against UV-induced apoptosis and cell death having additive effects. Although the protective effect of IGF-I involved activation of AKT, it was not affected by PKC{eta} expression, suggesting that PKC{eta} acts through a different route to increase cell survival. Hence, our studies show that PKC{eta} provides negative control on AKT pathway leading to reduced cell proliferation, and further suggest that its presence/absence in breast cancer cells will affect cell death, which could be of therapeutic value.« less
Neural activity to a partner's facial expression predicts self-regulation after conflict.
Hooker, Christine I; Gyurak, Anett; Verosky, Sara C; Miyakawa, Asako; Ayduk, Ozlem
2010-03-01
Failure to self-regulate after an interpersonal conflict can result in persistent negative mood and maladaptive behaviors. Research indicates that lateral prefrontal cortex (LPFC) activity is related to emotion regulation in response to laboratory-based affective challenges, such as viewing emotional pictures. This suggests that compromised LPFC function may be a risk factor for mood and behavior problems after an interpersonal conflict. However, it remains unclear whether LPFC activity to a laboratory-based affective challenge predicts self-regulation in real life. We investigated whether LPFC activity to a laboratory-based affective challenge (negative facial expressions of a partner) predicts self-regulation after a real-life affective challenge (interpersonal conflict). During a functional magnetic resonance imaging scan, healthy, adult participants in committed relationships (n = 27) viewed positive, negative, and neutral facial expressions of their partners. In a three-week online daily diary, participants reported conflict occurrence, level of negative mood, rumination, and substance use. LPFC activity in response to the laboratory-based affective challenge predicted self-regulation after an interpersonal conflict in daily life. When there was no interpersonal conflict, LPFC activity was not related to mood or behavior the next day. However, when an interpersonal conflict did occur, ventral LPFC (VLPFC) activity predicted mood and behavior the next day, such that lower VLPFC activity was related to higher levels of negative mood, rumination, and substance use. Low LPFC function may be a vulnerability and high LPFC function may be a protective factor for the development of mood and behavior problems after an interpersonal stressor. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Neural activity to a partner's facial expression predicts self-regulation after conflict
Hooker, Christine I.; Gyurak, Anett; Verosky, Sara; Miyakawa, Asako; Ayduk, Özlem
2009-01-01
Introduction Failure to self-regulate after an interpersonal conflict can result in persistent negative mood and maladaptive behaviors. Research indicates that lateral prefrontal cortex (LPFC) activity is related to the regulation of emotional experience in response to lab-based affective challenges, such as viewing emotional pictures. This suggests that compromised LPFC function may be a risk-factor for mood and behavior problems after an interpersonal stressor. However, it remains unclear whether LPFC activity to a lab-based affective challenge predicts self-regulation in real-life. Method We investigated whether LPFC activity to a lab-based affective challenge (negative facial expressions of a partner) predicts self-regulation after a real-life affective challenge (interpersonal conflict). During an fMRI scan, healthy, adult participants in committed, dating relationships (N = 27) viewed positive, negative, and neutral facial expressions of their partners. In an online daily-diary, participants reported conflict occurrence, level of negative mood, rumination, and substance-use. Results LPFC activity in response to the lab-based affective challenge predicted self-regulation after an interpersonal conflict in daily life. When there was no interpersonal conflict, LPFC activity was not related to the change in mood or behavior the next day. However, when an interpersonal conflict did occur, ventral LPFC (VLPFC) activity predicted the change in mood and behavior the next day, such that lower VLPFC activity was related to higher levels of negative mood, rumination, and substance-use. Conclusions Low LPFC function may be a vulnerability and high LPFC function may be a protective factor for the development of mood and behavior problems after an interpersonal stressor. PMID:20004365
ERIC Educational Resources Information Center
Jones, Diane Carlson; Cumberland, Amanda; Abbey, Belynda Bowling
1998-01-01
Two studies investigated emotional-display-rule knowledge and its associations with family expressiveness and peer competence. Findings indicated that third graders combined expression regulation with prosocial reasoning, norm-maintenance, and self-protective motives more frequently than kindergartners. Negative expressiveness was related…
Dvorak, Robert D; Pearson, Matthew R; Neighbors, Clayton; Martens, Matthew P
2015-06-01
Heavy alcohol use remains a consistent public health concern on college campuses. The current pilot study used deviance regulation theory (DRT) to modify protective behavioral strategies (PBS) among college student drinkers to reduce alcohol use and alcohol-related consequences. The sample was comprised of current college student drinkers (n = 76; 53.95% female) ranging in age from 18-24 (M = 19.29, SD = 1.42). Participants were randomly assigned to receive a positively or negatively framed message. They then reported on use of alcohol PBS (via the Protective Behavioral Strategies Scale), alcohol consumption (via the Modified Daily Drinking Questionnaire), and alcohol-related consequences (via the Young Adult Alcohol Consequences Questionnaire) each week for 6 weeks. Among drinkers with low PBS use norms, a positively, versus a negatively, framed message resulted in increased PBS use and consequently less alcohol consumption and fewer alcohol-related consequences. Among drinkers with high PBS use norms, a negatively, versus positively, framed message resulted in increased PBS use and consequently lower alcohol consumption and fewer alcohol-related consequences. However, these effects were only relevant among those who strongly believed the DRT frame. Findings suggest assigning drinkers to frames based on perceived PBS use norms and increasing belief in the frame may be 1 approach to increasing responsible drinking patterns among college students. Furthermore, the current data suggests important boundary conditions for norm-based interventions. (c) 2015 APA, all rights reserved).
Hyun, Jinshil; Sliwinski, Martin J; Almeida, David M; Smyth, Joshua M; Scott, Stacey B
2018-05-01
Given that the association between work stress and negative affect can exacerbate negative health and workplace outcomes, it is important to identify the protective and risk factors that moderate this association. Socioemotional aging and cognitive abilities might influence how people utilize emotion regulation skills and engage in practical problem solving to manage their work stress. The aim of this study is to examine whether age and cognitive abilities independently and interactively moderate the association between work-related stress and negative affect. A diverse working adult sample (N = 139, age 25-65, 69% of females) completed a cross-sectional survey that assessed chronic work stress, negative affect, and fluid and crystallized cognitive abilities. Results from regression analyses suggested that both fluid and crystallized cognitive abilities, but not age, moderated the association between work stress and negative affect. Further, we found that crystallized cognition had a stronger attenuating effect on the work stress-negative affect association for older compared to younger workers. The moderating effect of fluid cognition was invariant across age. Our findings demonstrate that cognitive abilities are an important personal resource that might protect individuals against the negative impacts of work stress and negative affect. Although the role that fluid cognition plays in work stress-negative affect association is comparably important for both younger and older workers, crystallized cognition might play a more valuable role for older than younger workers.
An, Wei; Nadeau, Scott A.; Mohapatra, Bhopal C.; Feng, Dan; Zutshi, Neha; Storck, Matthew D.; Arya, Priyanka; Talmadge, James E.; Meza, Jane L.; Band, Vimla; Band, Hamid
2015-01-01
Cbl and Cbl-b are tyrosine kinase-directed RING finger type ubiquitin ligases (E3s) that negatively regulate cellular activation pathways. E3 activity-disrupting human Cbl mutations are associated with myeloproliferative disorders (MPD) that are reproduced in mice with Cbl RING finger mutant knock-in or hematopoietic Cbl and Cbl-b double knockout. However, the role of Cbl proteins in hematopoietic stem cell (HSC) homeostasis, especially in the context of MPD is unclear. Here we demonstrate that HSC expansion and MPD development upon combined Cbl and Cbl-b deletion are dependent on HSCs. Cell cycle analysis demonstrated that DKO HSCs exhibit reduced quiescence associated with compromised reconstitution ability and propensity to undergo exhaustion. We show that sustained c-Kit and FLT3 signaling in DKO HSCs promotes loss of colony-forming potential, and c-Kit or FLT3 inhibition in vitro protects HSCs from exhaustion. In vivo, treatment with 5-fluorouracil hastens DKO HSC exhaustion and protects mice from death due to MPD. Our data reveal a novel and leukemia therapy-relevant role of Cbl and Cbl-b in the maintenance of HSC quiescence and protection against exhaustion, through negative regulation of tyrosine kinase-coupled receptor signaling. PMID:25871390
Lightning strike protection of composites
NASA Astrophysics Data System (ADS)
Gagné, Martin; Therriault, Daniel
2014-01-01
Aircraft structures are being redesigned to use fiber-reinforced composites mainly due to their high specific stiffness and strength. One of the main drawbacks from changing from electrically conductive metals to insulating or semi-conducting composites is the higher vulnerability of the aircraft to lightning strike damage. The current protection approach consists of bonding a metal mesh to the surface of the composite structure, but this weight increase negatively impact the fuel efficiency. This review paper presents an overview of the lightning strike problematic, the regulations, the lightning damage to composite, the current protection solutions and other material or technology alternatives. Advanced materials such as polymer-based nanocomposites and carbon nanotube buckypapers are promising candidates for lightweight lightning strike protection technology.
Diab, Safwat Y; Isosävi, Sanna; Qouta, Samir R; Kuittinen, Saija; Punamäki, Raija-Leena
2018-02-01
War survivors use multiple cognitive and emotional processes to protect their mental health from the negative impacts of trauma. Because mothers and infants may be especially vulnerable to trauma in conditions of war, it is urgent to determine which cognitive and emotional processes are effective for preventing negative trauma impacts." This study examined whether mothers' high posttraumatic growth (PTG) and positive posttraumatic cognitions (PTC) protected (a) their own mental health and (b) their infants' stress regulation and sensorimotor and language development from the effects of war trauma. The participants were 511 Palestinian mothers and their infants living in the Gaza strip. The mothers were interviewed in their second trimester of pregnancy (T1) as well as when the infant was four months (T2) and twelve months (T3). Mothers reported posttraumatic growth (PTG; Tedeschi & Calhoun, 1996) at T1 and posttraumatic cognitions (PTCI; Foa et al., 1999) at T2. They also reported their exposure to traumatic war events both at T1 and T3 and described their mental health conditions (e.g., PTSD and/or depressive and dissociation symptoms) at T3. The Infant Behaviour Questionnaire (IBQ) was used to measure infants' stress regulation at T2 and sensorimotor and language development at T3. The results, based on regression analyses with interaction terms between trauma and PTG, showed that high levels of traumatic war events were not associated with high levels of PTSD, depressive, or dissociation symptoms among mothers showing high levels of PTG. This suggests that PTG may protect maternal mental health from the effects of trauma. In turn, positive maternal PTCs appeared to protect the infants' stress regulation from the effects of war trauma. The study concludes by discussing ways to develop and implement preventive interventions for mother-infant dyads in war conditions. Copyright © 2017 Elsevier Inc. All rights reserved.
DDX3X RNA helicase affects breast cancer cell cycle progression by regulating expression of KLF4.
Cannizzaro, Ester; Bannister, Andrew John; Han, Namshik; Alendar, Andrej; Kouzarides, Tony
2018-05-21
DDX3X is a multifunctional RNA helicase with documented roles in different cancer types. Here, we demonstrate that DDX3X plays an oncogenic role in breast cancer cells by modulating the cell cycle. Depletion of DDX3X in MCF7 cells slows cell proliferation by inducing a G1 phase arrest. Notably, DDX3X inhibits expression of Kruppel-like factor 4 (KLF4), a transcription factor and cell cycle repressor. Moreover, DDX3X directly interacts with KLF4 mRNA and regulates its splicing. We show that DDX3X-mediated repression of KLF4 promotes expression of S-phase inducing genes in MCF7 breast cancer cells. These findings provide evidence for a novel function of DDX3X in regulating expression and downstream functions of KLF4, a master negative regulator of the cell cycle. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Rocha-Jiménez, Teresita; Brouwer, Kimberly C; Silverman, Jay G; Morales-Miranda, Sonia; Goldenberg, Shira M
2017-10-01
Public health regulations practices surrounding sex work and their enforcement can have unintended consequences for HIV and sexually transmitted infection (STI) prevention and care among sex workers. This analysis was based on qualitative in-depth (n = 33) and focus groups interviews (n = 20) conducted with migrant female sex workers in Tecún Umán and Quetzaltenango, Guatemala, and explored the implementation of sex work regulations and related consequences for HIV prevention and care among migrant sex workers. Sex work regulations were found to have health-related benefits (e.g., access to HIV/STI testing) as well as negative impacts, such as abuse by police and harassment, detention/deportation of migrant sex workers. Whereas public health regulations may improve access to HIV/STI testing, their implementation may inadvertently jeopardize sex workers' health through unintended negative consequences. Non-coercive, evidence-based public health and sex work policies and programs are needed to expand access to HIV/STI prevention and care among migrant sex workers, while protecting their dignity and human rights.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chengye, Zhan; Daixing, Zhou, E-mail: dxzhou7246@hotmail.com; Qiang, Zhong
2013-09-13
Highlights: •First time to display that LPS downregulate the expression of PRC. •First time to show that PRC inhibits the induction of VCAM-1 and E-selectin. •First time to show that PRC inhibit monocytes attachment to endothelial cells. •First time to display that PRC inhibits transcriptional activity of NF-κB. •PRC protects the respiration rate and suppresses the glycolysis rate against LPS. -- Abstract: PGC-1-related coactivator (PRC) is a growth-regulated transcriptional cofactor known to activate many of the nuclear genes specifying mitochondrial respiratory function. Endothelial dysfunction is a prominent feature found in many inflammatory diseases. Adhesion molecules, such as VCAM-1, mediate themore » attachment of monocytes to endothelial cells, thereby playing an important role in endothelial inflammation. The effects of PRC in regards to endothelial inflammation remain unknown. In this study, our findings show that PRC can be inhibited by the inflammatory cytokine LPS in cultured human umbilical vein endothelial cells (HUVECs). In the presence of LPS, the expression of endothelial cell adhesion molecular, such as VCAM1 and E-selectin, is found to be increased. These effects can be negated by overexpression of PRC. Importantly, monocyte adhesion to endothelial cells caused by LPS is significantly attenuated by PRC. In addition, overexpression of PRC protects mitochondrial metabolic function and suppresses the rate of glycolysis against LPS. It is also found that overexpression of PRC decreases the transcriptional activity of NF-κB. These findings suggest that PRC is a negative regulator of endothelial inflammation.« less
MicroRNA-137 Negatively Regulates H2O2-Induced Cardiomyocyte Apoptosis Through CDC42
Wang, Junnan; Xu, Rihao; Wu, Junduo; Li, Zhibo
2015-01-01
Background Oxidative stress, inducing cardiomyocyte apoptosis or myocardial ischemia, is the major denominator of many cardiac diseases. In this study, we intended to explore the regulatory function of microRNA-137 (miR-137) in oxidative stress-induced cardiomyocyte apoptosis. Material/Methods Cardiomyocytes were extracted from newborn C57BL/6 mice and cultured in vitro. Apoptosis was induced by H2O2, and evaluated by TUNEL assay. The effect of cardiomyocyte apoptosis on gene expression of miR-137 was evaluated by qRT-PCR. Lentivirus was used to stably down-regulate miR-137, and the subsequent effects of miR-137 down-regulation on cardiomyocyte apoptosis, its targeted gene CDC42, and caspase pathway were evaluated by TUNEL assay, dual-luciferase reporter assay, and Western blot assay, respectively. Finally, CDC42 was down-regulated by siRNA and its effect on miR-137-mediated cardiomyocyte apoptosis protection was examined. Results H2O2 induced significant apoptosis and up-regulated miR-137 in cardiomyocytes, whereas lentivirus-mediated miR-137 down-regulation protected against apoptosis. CDC42 was the direct target gene of miR-137 and proteins of CDC42, caspase-3, and caspase-9 were all regulated by miR-137 down-regulation in cardiomyocyte apoptosis. SiRNA-mediated CDC42 down-regulation reversed the protection of miR-137 down-regulation against cardiomyocyte apoptosis. Conclusions Our work demonstrated miR-137 and CDC42 are critical regulators in cardiomyocyte apoptosis. It may help to identify the molecular targets to prevent myocardial injury in human patients. PMID:26566162
AMP-activated protein kinase protects against necroptosis via regulation of Keap1-PGAM5 complex.
Wang, Yi-Shu; Yu, Peng; Wang, Yong; Zhang, Jing; Hang, Wei; Yin, Zhi-Xian; Liu, Gang; Chen, Jianfeng; Werle, Kaitlin D; Quan, Cheng-Shi; Gao, Hang; Zeng, Qinghua; Cui, Rutao; Liang, Jiyong; Ding, Qiang; Li, Yu-Lin; Xu, Zhi-Xiang
2018-05-15
The AMP-activated protein kinase (AMPK) plays critical roles in growth regulation and metabolism reprogramming. AMPK activation protects cells against apoptosis from injury in different cell and animal models. However, its function in necroptosis remains largely unclear. In the current study, we demonstrated that AMPK was activated upon necroptosis induction and protected mouse embryonic fibroblasts (MEFs) and cardiomyocytes from N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and reactive oxygen species (ROS) induced necroptosis. Activation of AMPK with chemicals A-769662, 2-deoxyglucose (2-DG), and metformin or constitutively active (CA) AMPK markedly decreased necroptosis and cytotoxicity induced by MNNG. In contrast, AMPK inhibitor compound C, dominant negative (DN) AMPK, as well as AMPK shRNAs increased necroptosis and cytotoxicity induced by MNNG. We further showed that AMPK physically associated with a protein complex containing PGAM5 and Keap1 whereby facilitating Keap1-mediated PGAM5 ubiquitination upon necroptosis induction. The AMPK agonist metformin ameliorated myocardial ischemia and reperfusion (IR) injury and reduced necroptosis through down-regulating the expression of PGAM5 in the Langendorff-perfused rat hearts. Activation of AMPK protects against necroptosis via promoting Keap1-mediated PGAM5 degradation. Metformin may act as a valuable agent for the protection of myocardial ischemia and reperfusion injury by activating AMPK and reducing necroptosis. Copyright © 2018. Published by Elsevier B.V.
USDA-ARS?s Scientific Manuscript database
Breast cancer is the second leading cause of death in the Western hemisphere, affecting one of eight women in their lifetime. In addition to chromosomal and genetic alterations, nutrition is considered a risk determinant for breast cancer. Prevailing evidence suggests a negative correlation between ...
Research Resource: Aorta- and Liver-Specific ERα-Binding Patterns and Gene Regulation by Estrogen
Gordon, Francesca K.; Vallaster, Caroline S.; Westerling, Thomas; Iyer, Lakshmanan K.; Brown, Myles
2014-01-01
Estrogen has vascular protective effects in premenopausal women and in women younger than 60 years who are receiving hormone replacement therapy. However, estrogen also increases the risks of breast and uterine cancers and of venous thromboses linked to up-regulation of coagulation factors in the liver. In mouse models, the vasculoprotective effects of estrogen are mediated by the estrogen receptor α (ERα) transcription factor. Here, through next-generation sequencing approaches, we show that almost all of the genes regulated by 17β-estradiol (E2) differ between mouse aorta and mouse liver, ex vivo, and that this difference is associated with a distinct genomewide distribution of ERα on chromatin. Bioinformatic analysis of E2-regulated promoters and ERα binding site sequences identify several transcription factors that may determine the tissue specificity of ERα binding and E2-regulated genes, including the enrichment of NF-κB, AML1, and AP1 sites in the promoters of E2 down-regulated inflammatory genes in aorta but not liver. The possible vascular-specific functions of these factors suggest ways in which the protective effects of estrogen could be promoted in the vasculature without incurring negative effects in other tissues. PMID:24992180
Xu, Dongmei; Liu, Guang; Cheng, Lin; Lu, Xinhua; Chen, Wenqing; Deng, Zixin
2013-01-01
Background Muraymycin, a potent translocase I (MraY) inhibitor, is produced by Streptomyces sp. NRRL30471. The muraymycin gene cluster (mur) was recently cloned, and bioinformatic analysis of mur34 revealed its encoding product exhibits high homology to a large family of proteins, including KanI and RacI in individual biosynthetic pathway of kanamycin and ribostamycin. However, the precise role of these proteins remains unknown. Principal Findings Here we report the identification of Mur34 as the novel negative regulator involved in muraymycin biosynthesis. Independent disruption of mur34 on chromosome and cosmid directly resulted in significant improvement of muraymycin production by at least 10 folds, thereof confirming the negative function of Mur34 during muraymycin biosynthesis and realizing the engineered production of muraymycin in heterologous host. Gene expression analysis indicated that the transcription level of the mur genes in mur34 mutant (DM-5) was dramatically enhanced by ca. 30 folds. Electrophoretic mobility shift assay (EMSA) showed that Mur34 specifically bound to the promoter region of mur33. Further experiments showed that a 28-bp region downstream of the transcription start point (TSP) was protected by His6Mur34, and the −10 region is essential for the activity of mur33 promoter. Conclusions Mur34 plays an unambiguously negative role in muraymycin biosynthesis via binding to the upstream of mur33. More importantly, Mur34 represents a novel family of regulators acting in negative manner to regulate the secondary metabolites biosynthesis in bacteria. PMID:24143177
Liu, Yang; Jiang, Guoqiao; Cui, Yaya; Mukherjee, Asita; Ma, Wei Lei; Chatterjee, Arun K.
1999-01-01
Erwinia carotovora subsp. carotovora produces extracellular pectate lyase (Pel), polygalacturonase (Peh), cellulase (Cel), and protease (Prt). The concerted actions of these enzymes largely determine the virulence of this plant-pathogenic bacterium. E. carotovora subsp. carotovora also produces HarpinEcc, the elicitor of the hypersensitive reaction. We document here that KdgREcc (Kdg, 2-keto-3-deoxygluconate; KdgR, general repressor of genes involved in pectin and galacturonate catabolism), a homolog of the E. chrysanthemi repressor, KdgREch and the Escherichia coli repressor, KdgREco, negatively controls not only the pectinases, Pel and Peh, but also Cel, Prt, and HarpinEcc production in E. carotovora subsp. carotovora. The levels of pel-1, peh-1, celV, and hrpNEcc transcripts are markedly affected by KdgREcc. The KdgREcc− mutant is more virulent than the KdgREcc+ parent. Thus, our data for the first time establish a global regulatory role for KdgREcc in E. carotovora subsp. carotovora. Another novel observation is the negative effect of KdgREcc on the transcription of rsmB (previously aepH), which specifies an RNA regulator controlling exoenzyme and HarpinEcc production. The levels of rsmB RNA are higher in the KdgREcc− mutant than in the KdgREcc+ parent. Moreover, by DNase I protection assays we determined that purified KdgREcc protected three 25-bp regions within the transcriptional unit of rsmB. Alignment of the protected sequences revealed the 21-mer consensus sequence of the KdgREcc-binding site as 5′-G/AA/TA/TGAAA[N6]TTTCAG/TG/TA-3′. Two such KdgREcc-binding sites occur in rsmB DNA in a close proximity to each other within nucleotides +79 and +139 and the third KdgREcc-binding site within nucleotides +207 and +231. Analysis of lacZ transcriptional fusions shows that the KdgR-binding sites negatively affect the expression of rsmB. KdgREcc also binds the operator DNAs of pel-1 and peh-1 genes and represses expression of a pel1-lacZ and a peh1-lacZ transcriptional fusions. We conclude that KdgREcc affects extracellular enzyme production by two ways: (i) directly, by inhibiting the transcription of exoenzyme genes; and (ii) indirectly, by preventing the production of a global RNA regulator. Our findings support the idea that KdgREcc affects transcription by promoter occlusion, i.e., preventing the initiation of transcription, and by a roadblock mechanism, i.e., by affecting the elongation of transcription. PMID:10198003
Gewirtz, Andrew T; Vijay-Kumar, Matam; Brant, Steven R; Duerr, Richard H; Nicolae, Dan L; Cho, Judy H
2006-06-01
Crohn's disease (CD) is associated with elevated adaptive immunity to commensal microbes, with flagellin being a dominant antigen. In light of heightened awareness of the importance of innate immunity in regulating adaptive immunity and ambiguity as to the role of CD-associated immune responses in CD pathophysiology, we sought to determine whether natural acquisition of immune responses to flagellin were regulated by the innate immune flagellin receptor toll-like receptor 5 (TLR5) and determine whether persons carrying a recently defined common dominant-negative TLR5 polymorphism (TLR5-stop) might be protected from developing CD. Carriage rates of a recently defined dominant-negative TLR5 polymorphism (TLR5-stop) and levels of serum immunoreactivity to bacterial products were measured in inflammatory bowel disease patients, first-degree relatives, and unrelated controls. We observed that, in healthy subjects, persons carrying TLR5-stop had significantly lower levels of flagellin-specific IgG and IgA but had similar levels of total and LPS-specific Ig. Moreover, we observed that, among Jewish subjects, the carriage rate of TLR5-stop (in heterozygous state) was significantly less in CD patients, but not ulcerative colitis (UC) patients, compared with unaffected relatives and unrelated controls (5.4, 0.9, 6.0, and 6.5% for unaffected relatives, CD, UC, and unrelated Jewish controls, respectively, n = 296, 215, 185, and 416, respectively; P = 0.037 by likelihood calculation for CD vs. controls), indicating that TLR5-stop can protect persons of Jewish ethnicity against CD. We did not observe a significant association of TLR5-stop with CD in a non-Jewish cohort (11.1, 10.4, and 11.7% for unaffected relatives, CD, and UC, respectively; n = 841, 543, and 300 for unaffected relatives, respectively). These results demonstrate that natural acquisition of immune responses to flagellin are regulated by TLR5 and suggest that immune responses to flagellin are not merely associated with CD but rather promote the pathogenic response.
Gollan, Peter J.; Lima-Melo, Yugo; Tiwari, Arjun; Tikkanen, Mikko
2017-01-01
The photosynthetic light reactions provide energy that is consumed and stored in electron sinks, the products of photosynthesis. A balance between light reactions and electron consumption in the chloroplast is vital for plants, and is protected by several photosynthetic regulation mechanisms. Photosystem I (PSI) is particularly susceptible to photoinhibition when these factors become unbalanced, which can occur in low temperatures or in high light. In this study we used the pgr5 Arabidopsis mutant that lacks ΔpH-dependent regulation of photosynthetic electron transport as a model to study the consequences of PSI photoinhibition under high light. We found that PSI damage severely inhibits carbon fixation and starch accumulation, and attenuates enzymatic oxylipin synthesis and chloroplast regulation of nuclear gene expression after high light stress. This work shows that modifications to regulation of photosynthetic light reactions, which may be designed to improve yield in crop plants, can negatively impact metabolism and signalling, and thereby threaten plant growth and stress tolerance. This article is part of the themed issue ‘Enhancing photosynthesis in crop plants: targets for improvement’. PMID:28808104
Ó'Léime, Ciarán S; Kozareva, Danka A; Hoban, Alan E; Long-Smith, Caitriona M; Cryan, John F; Nolan, Yvonne M
2018-02-01
Hippocampal neurogenesis is a lifelong process whereby new neurons are produced and integrate into the host circuitry within the hippocampus. It is regulated by a multitude of extrinsic and intrinsic regulators and is believed to contribute to certain hippocampal-dependent cognitive tasks. Hippocampal neurogenesis and associated cognition have been demonstrated to be impaired after increases in the levels of proinflammatory cytokine IL-1β in the hippocampus, such as that which occurs in various neurodegenerative and psychiatric disorders. IL-1β also suppresses the expression of TLX (orphan nuclear receptor tailless homolog), which is an orphan nuclear receptor that functions to promote neural progenitor cell (NPC) proliferation and suppress neuronal differentiation; therefore, manipulation of TLX represents a potential strategy with which to prevent the antiproliferative effects of IL-1β. In this study, we assessed the mechanism that underlies IL-1β-induced changes in TLX expression and determined the protective capacity of TLX to mitigate the effects of IL-1β on embryonic rat hippocampal neurosphere expansion. We demonstrate that IL-1β activated the NF-κB pathway in proliferating NPCs and that this activation was responsible for IL-1β-induced changes in TLX expression. In addition, we report that enhancing TLX expression prevented the IL-1β-induced suppression of neurosphere expansion. Thus, we highlight TLX as a potential protective regulator of the antiproliferative effects of IL-1β on hippocampal neurogenesis.-Ó'Léime, C. S., Kozareva, D. A., Hoban, A. E., Long-Smith, C. M., Cryan, J. F., Nolan, Y. M. TLX is an intrinsic regulator of the negative effects of IL-1β on proliferating hippocampal neural progenitor cells.
TOR-mediated autophagy regulates cell death in Drosophila neurodegenerative disease.
Wang, Tao; Lao, Uyen; Edgar, Bruce A
2009-09-07
Target of rapamycin (TOR) signaling is a regulator of cell growth. TOR activity can also enhance cell death, and the TOR inhibitor rapamycin protects cells against proapoptotic stimuli. Autophagy, which can protect against cell death, is negatively regulated by TOR, and disruption of autophagy by mutation of Atg5 or Atg7 can lead to neurodegeneration. However, the implied functional connection between TOR signaling, autophagy, and cell death or degeneration has not been rigorously tested. Using the Drosophila melanogaster visual system, we show in this study that hyperactivation of TOR leads to photoreceptor cell death in an age- and light-dependent manner and that this is because of TOR's ability to suppress autophagy. We also find that genetically inhibiting TOR or inducing autophagy suppresses cell death in Drosophila models of Huntington's disease and phospholipase C (norpA)-mediated retinal degeneration. Thus, our data indicate that TOR induces cell death by suppressing autophagy and provide direct genetic evidence that autophagy alleviates cell death in several common types of neurodegenerative disease.
Positive Gene Regulation by a Natural Protective miRNA Enables Arbuscular Mycorrhizal Symbiosis.
Couzigou, Jean-Malo; Lauressergues, Dominique; André, Olivier; Gutjahr, Caroline; Guillotin, Bruno; Bécard, Guillaume; Combier, Jean-Philippe
2017-01-11
Arbuscular mycorrhizal (AM) symbiosis associates most plants with fungi of the phylum Glomeromycota. The fungus penetrates into roots and forms within cortical cell branched structures called arbuscules for nutrient exchange. We discovered that miR171b has a mismatched cleavage site and is unable to downregulate the miR171 family target gene, LOM1 (LOST MERISTEMS 1). This mismatched cleavage site is conserved among plants that establish AM symbiosis, but not in non-mycotrophic plants. Unlike other members of the miR171 family, miR171b stimulates AM symbiosis and is expressed specifically in root cells that contain arbuscules. MiR171b protects LOM1 from negative regulation by other miR171 family members. These findings uncover a unique mechanism of positive post-transcriptional regulation of gene expression by miRNAs and demonstrate its relevance for the establishment of AM symbiosis. Copyright © 2017 Elsevier Inc. All rights reserved.
Dynamic control of type I IFN signalling by an integrated network of negative regulators.
Porritt, Rebecca A; Hertzog, Paul J
2015-03-01
Whereas type I interferons (IFNs) have critical roles in protection from pathogens, excessive IFN responses contribute to pathology in both acute and chronic settings, pointing to the importance of balancing activating signals with regulatory mechanisms that appropriately tune the response. Here we review evidence for an integrated network of negative regulators of IFN production and action, which function at all levels of the activating and effector signalling pathways. We propose that the aim of this extensive network is to limit tissue damage while enabling an IFN response that is temporally appropriate and of sufficient magnitude. Understanding the architecture and dynamics of this network, and how it differs in distinct tissues, will provide new insights into IFN biology and aid the design of more effective therapeutics. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Tang, Shui-Yan; Li, Pansy Honying; Fryxell, Gerald E.; Lo, Carlos Wing-Hung
2015-09-01
This study examines the effects of internal motivations and external pressures on the integration of environmental management (EM) practices within manufacturing operations in China. The moderating role of perceptions toward the regulatory process is also considered along with comparisons between wholly Chinese-owned and foreign-owned enterprises. From a sample of 131 manufacturing companies in the Guangzhou area, it was found that the salience of fees and fines has a strong positive influence on perceptions toward the regulator (the local Environmental Protection Bureau, EPB). This also has a positive effect on perceptions toward regulations themselves for foreign-owned enterprises. Business-case motivations for EM positively shape enterprise perceptions toward regulations, whereas risk-reduction motivations have a negative effect on perceptions toward regulations in foreign-owned enterprises. Enterprise perceptions toward the regulatory process have direct effects on the integration of EM practices in wholly Chinese-owned enterprises, but in opposite directions. While positive perceptions toward regulations have positive influence, positive perceptions toward regulators (i.e., the EPB) negatively affect it. Overall, these results indicated that promoting the adoption of EM practices depends on convincing business leaders that EM practices contribute to profit making. The regulatory process can potentially promote these practices, but measures need to be taken to ensure that the regulator is not co-opted by the regulated, especially in wholly Chinese-owned enterprises.
Tang, Shui-Yan; Li, Pansy Honying; Fryxell, Gerald E; Lo, Carlos Wing-Hung
2015-09-01
This study examines the effects of internal motivations and external pressures on the integration of environmental management (EM) practices within manufacturing operations in China. The moderating role of perceptions toward the regulatory process is also considered along with comparisons between wholly Chinese-owned and foreign-owned enterprises. From a sample of 131 manufacturing companies in the Guangzhou area, it was found that the salience of fees and fines has a strong positive influence on perceptions toward the regulator (the local Environmental Protection Bureau, EPB). This also has a positive effect on perceptions toward regulations themselves for foreign-owned enterprises. Business-case motivations for EM positively shape enterprise perceptions toward regulations, whereas risk-reduction motivations have a negative effect on perceptions toward regulations in foreign-owned enterprises. Enterprise perceptions toward the regulatory process have direct effects on the integration of EM practices in wholly Chinese-owned enterprises, but in opposite directions. While positive perceptions toward regulations have positive influence, positive perceptions toward regulators (i.e., the EPB) negatively affect it. Overall, these results indicated that promoting the adoption of EM practices depends on convincing business leaders that EM practices contribute to profit making. The regulatory process can potentially promote these practices, but measures need to be taken to ensure that the regulator is not co-opted by the regulated, especially in wholly Chinese-owned enterprises.
Power supply system for negative ion source at IPR
NASA Astrophysics Data System (ADS)
Gahlaut, Agrajit; Sonara, Jashwant; Parmar, K. G.; Soni, Jignesh; Bandyopadhyay, M.; Singh, Mahendrajit; Bansal, Gourab; Pandya, Kaushal; Chakraborty, Arun
2010-02-01
The first step in the Indian program on negative ion beams is the setting up of Negative ion Experimental Assembly - RF based, where 100 kW of RF power shall be coupled to a plasma source producing plasma of density ~5 × 1012 cm-3, from which ~ 10 A of negative ion beam shall be produced and accelerated to 35 kV, through an electrostatic ion accelerator. The experimental system is modelled similar to the RF based negative ion source, BATMAN presently operating at IPP, Garching, Germany. The mechanical system for Negative Ion Source Assembly is close to the IPP source, remaining systems are designed and procured principally from indigenous sources, keeping the IPP configuration as a base line. High voltage (HV) and low voltage (LV) power supplies are two key constituents of the experimental setup. The HV power supplies for extraction and acceleration are rated for high voltage (~15 to 35kV), and high current (~ 15 to 35A). Other attributes are, fast rate of voltage rise (< 5ms), good regulation (< ±1%), low ripple (< ±2%), isolation (~50kV), low energy content (< 10J) and fast cut-off (< 100μs). The low voltage (LV) supplies required for biasing and providing heating power to the Cesium oven and the plasma grids; have attributes of low ripple, high stability, fast and precise regulation, programmability and remote operation. These power supplies are also equipped with over-voltage, over-current and current limit (CC Mode) protections. Fault diagnostics, to distinguish abnormal rise in currents (breakdown faults) with over-currents is enabled using fast response breakdown and over-current protection scheme. To restrict the fault energy deposited on the ion source, specially designed snubbers are implemented in each (extraction and acceleration) high voltage path to swap the surge energy. Moreover, the monitoring status and control signals from these power supplies are required to be electrically (~ 50kV) isolated from the system. The paper shall present the design basis, topology selection, manufacturing, testing, commissioning, integration and control strategy of these HVPS. A complete power interconnection scheme, which includes all protective devices and measuring devices, low & high voltage power supplies, monitoring and control signals etc. shall also be discussed. The paper also discusses the protocols involved in grounding and shielding, particularly in operating the system in RF environment.
Bonifield, Heather R.; Yamaguchi, Shigeru; Hughes, Kelly T.
2000-01-01
We investigated the posttranscriptional regulation of flgE, a class 2 gene that encodes the hook subunit protein of the flagella. RNase protection assays demonstrated that the flgE gene was transcribed at comparable levels in numerous strains defective in known steps of flagellar assembly. However, Western analyses of these strains demonstrated substantial differences in FlgE protein levels. Although wild-type FlgE levels were observed in strains with deletions of genes encoding components of the switch complex and the flagellum-specific secretion apparatus, no protein was detected in a strain with deletions of the rod, ring, and hook-associated proteins. To determine whether FlgE levels were affected by the stage of hook–basal-body assembly, Western analysis was performed on strains with mutations at individual loci encompassed by the deletion. FlgE protein was undetectable in rod mutants, intermediate in ring mutants, and wild type in hook-associated protein mutants. The lack of negative regulation in switch complex and flagellum-specific secretion apparatus deletion mutants blocked for flagellar construction prior to rod assembly suggests that these structures play a role in the negative regulation of FlgE. Quantitative Western analyses of numerous flagellar mutants indicate that FlgE levels reflect the stage at which flagellar assembly is blocked. These data provide evidence for negative posttranscriptional regulation of FlgE in response to the stage of flagellar assembly. PMID:10869084
NASA Astrophysics Data System (ADS)
Missall, S.; Welp, M.; Thevs, N.; Abliz, A.; Halik, Ü.
2014-12-01
The city of Aksu, situated at the northern fringe of the Taklimakan Desert in the northwest of China, is exposed to periodic severe dust and sand storms. In 1986, local authorities decided to establish a peri-urban shelterbelt plantation, the so-called Kökyar Protection Forest. It was realised as a patchwork of poplar shelterbelts and orchards. The total area of the plantation reached 3800 ha in 2005. This endeavour was made possible by the annual mass mobilisation of Aksu citizens, based on the Chinese regulation of the "National Compulsory Afforestation Campaigns". Establishment costs amounted to ca. CNY 60 000 ha-1 (ca. USD 10 000 ha-1). The regulating ecosystem services provided by Kökyar Protection Forest clearly reduce dust and sand storm impacts on Aksu City. Permanent maintenance of the plantation is facilitated by leasing orchard plots to private fruit farmers. This system ensures forest tending, reduces government expenses, and provides incomes to farmers. From the perspective of the local economy, annual farming net benefits generated by Kökyar fruit farmers more than compensate annual government grants for maintenance, resulting in an overall monetary net benefit of at least CNY 10 500 ha-1 (ca. USD 1600 ha-1) on the long-term average. The intended regulating ecosystem services can thus be provided to the citizens of Aksu without payments for ecosystem services or other financial burdens. For a more complete understanding of Kökyar Protection Forest, future research should be directed towards quantifying the effect of its regulating ecosystem services, and on investigating the negative downstream consequences of its water consumption.
Ronald, Pamela C
2011-12-01
Control of Gram-negative bacterial infections of plants and animals remains a major challenge because conventional approaches are often not sufficient to eradicate these infections. One major reason for their persistence seems to be the capability of the bacteria to grow within biofilms that protect them from adverse environmental factors. Quorum sensing (QS) plays an important role in the formation of biofilms. In QS, small molecules serve as signals to recognize bacterial cell population size, leading to changes in expression of specific genes when a signal has accumulated to some threshold concentration. The small protein Ax21 (Activator of XA21-mediated immunity), serves as a QS factor that regulates biofilm formation and virulence in the Gram-negative bacterium, Xanthomonas oryzae pv. oryzae. Knowledge of small protein-mediated QS in Gram-negative bacteria can be used to develop new methods to control persistent Gram-negative infections. © Discovery Medicine
On the origin of the halo stabilization.
Trulsson, Martin; Jönsson, Bo; Labbez, Christophe
2013-01-14
Monte Carlo simulations show that charge-regulation alone can cause highly charged zirconium nanoparticles to adsorb to a similarly charged or neutral silica particle and thereby stabilizing the latter. This mechanism, referred to as halo stabilization, is quite general and applicable in a range of systems provided that pH, van der Waals forces, and dissociation constants of the charge-regulating particles are properly chosen. In our modeling we see an overall attraction at low volume fractions of nanoparticles, while at higher a repulsive barrier is created, stabilizing the microparticles and protecting them from aggregation. The charge-regulation mechanism also turns the silica surface from positively charged, without nanoparticles, to negatively charged in the presence of nanoparticles.
HOW SHOULD THE WELFARE OF FETAL AND NEUROLOGICALLY IMMATURE POSTNATAL ANIMALS BE PROTECTED?
Campbell, Madeleine L.H.; Mellor, David J.; Sandøe, Peter
2016-01-01
Legal protection of the welfare of prenatal animals has not previously been addressed as a discrete subject within the academic literature on animal welfare, ethics and law. This paper aims to rectify this by reviewing the protections (or absence of protections) provided for fetuses by existing legislation in various jurisdictions, and considering the extent to which legal protection of animal fetuses can be justified on animal welfare grounds. Questions related to the need to protect the welfare of neurologically immature postnatal animals are also considered. We argue that there are reasons to protect animal fetuses, both in order to protect fetuses themselves against possible suffering, and in order to protect the animals which fetuses will become against negative welfare impacts that originate prenatally. We review the science on whether fetuses can suffer, and argue that extant regulations do not fully reflect current scientific understanding. Following the precautionary principle, we further argue that regulators should consider the possibility that foetuses and neurologically immature postnatal animals may suffer due to subcortically based ‘raw basic affects’ (i.e. relatively undifferentiated experiences of discomfort suggested to be generated by neural processing at levels below the cerebral cortex). Furthermore we show that there are reasons for affording fetuses protection in order to safeguard the long-term welfare of future animals. However, it may be possible to provide such protection via rules or laws relating to the use of certain techniques and the management of pregnant animals, rather than via direct legal protection of fetuses themselves. In order to provide such protection effectively we need to know more about the relationship between maternal nutrition, stress, exercise, management and fetal health, and about the impact of the timing of a fetal insult on long-term postnatal welfare. PMID:26973382
Emotion regulation and culture: are the social consequences of emotion suppression culture-specific?
Butler, Emily A; Lee, Tiane L; Gross, James J
2007-02-01
Emotional suppression has been associated with generally negative social consequences (Butler et al., 2003; Gross & John, 2003). A cultural perspective suggests, however, that these consequences may be moderated by cultural values. We tested this hypothesis in a two-part study, and found that, for Americans holding Western-European values, habitual suppression was associated with self-protective goals and negative emotion. In addition, experimentally elicited suppression resulted in reduced interpersonal responsiveness during face-to-face interaction, along with negative partner-perceptions and hostile behavior. These deleterious effects were reduced when individuals with more Asian values suppressed, and these reductions were mediated by cultural differences in the responsiveness of the suppressors. These findings suggest that many of suppression's negative social impacts may be moderated by cultural values. (c) 2007 APA, all rights reserved.
Impact of toxic chemicals on local wastewater treatment plant and the environment
NASA Astrophysics Data System (ADS)
Bennett, Gary F.
1989-05-01
Because toxic chemicals being discharged to sewers were simultaneously interfering with wastewater treatment processes of municipal, biological treatment plants and were passing through these plants to negatively impact the bodies of water to which these plants were discharging, the U.S. Environmental Protection Agency issued regulations governing industrial discharges to municipal sewers. These “Pretreatment Regulations” limit industrial discharges to municipal sewers of heavy metals, oil and grease, acids and bases, and toxic organic chemicals. This paper discusses the evolution of these regulations, the basis for them, the types of regulations (categorical and local), and the rationale for their promulgation based on the impacts of toxics chemicals on the treatment plant and receiving system. Finally, the expected results of these regulations in reducing industrial discharges of toxic chemicals is discussed.
Feng, Xin; Shaw, Daniel S; Kovacs, Maria; Lane, Tonya; O'Rourke, Flannery E; Alarcon, Joseph H
2008-02-01
This study examined preschoolers' emotion regulation (ER) strategies and the association with temperament, maternal interactive style, and maternal history of childhood-onset depression (COD). Participants were 62 children and their mothers, 37 of whom had mothers with COD. Children's ER was assessed using a disappointment paradigm; temperament assessment also was laboratory-based. Maternal COD was inversely related to offspring's active ER and positive mood. Among children of COD mothers, behavioral inhibition was associated with passive regulation and sadness, and maternal positivity toward these children was associated with child active ER and positive mood. Behavioral inhibition may place children of COD mothers at risk for developing maladaptive ways of regulating negative emotion, whereas mothers' positivity may serve as a protective factor for them.
Singh, Mahendra Pratap; Kim, Ki Young; Kwak, Geun-Hee; Baek, Suk-Hwan; Kim, Hwa-Young
2017-10-01
Methionine sulfoxide reductase A (MsrA) is a major antioxidant enzyme that specifically catalyzes the reduction of methionine S-sulfoxide. In this study, we used MsrA gene-knockout (MsrA -/- ) mice and bone marrow-derived macrophages (BMDMs) to investigate the role of MsrA in the regulation of inflammatory responses induced by lipopolysaccharide (LPS). MsrA -/- mice were more susceptible to LPS-induced lethal shock than wild-type (MsrA +/+ ) mice. Serum levels of the proinflammatory cytokines IL-6 and TNF-α induced by LPS were higher in MsrA -/- than in MsrA +/+ mice. MsrA deficiency in the BMDMs also increased the LPS-induced cytotoxicity as well as TNF-α level. Basal and LPS-induced reactive oxygen species (ROS) levels were higher in MsrA -/- than in MsrA +/+ BMDMs. Phosphorylation levels of p38, JNK, and ERK were higher in MsrA -/- than in MsrA +/+ BMDMs in response to LPS, suggesting that MsrA deficiency increases MAPK activation. Furthermore, MsrA deficiency increased the expression and nuclear translocation of NF-κB and the expression of inducible nitric oxide synthase, a target gene of NF-κB, in response to LPS. Taken together, our results suggest that MsrA protects against LPS-induced septic shock, and negatively regulates proinflammatory responses via inhibition of the ROS-MAPK-NF-κB signaling pathways. Copyright © 2017 Elsevier Inc. All rights reserved.
Implicit interpretation biases affect emotional vulnerability: a training study.
Tran, Tanya B; Siemer, Matthias; Joormann, Jutta
2011-04-01
Cognitive theories of emotion propose that the interpretation of emotion-eliciting situations crucially shapes affective responses. Implicit or automatic biases in these interpretations may hinder emotion regulation and thereby increase risk for the onset and maintenance of psychological disorders. In this study, participants were randomly assigned to a positive or negative interpretation bias training using ambiguous social scenarios. After the completion of the training, a stress task was administered and changes in positive and negative affect and self-esteem were assessed. The results demonstrate that the interpretation bias training was successful in that participants exhibited a tendency to interpret novel scenarios in accordance with their training condition. Importantly, the positive training condition also had a protective effect on self-esteem. Participants in this condition did not exhibit a decrease in self-esteem after the stress task, whereas participants in the negative condition did. These results demonstrate that implicit cognitive biases can be trained and that this training affects self-esteem. Implications of these findings for research on psychopathology and emotion regulation are discussed. © 2011 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business
Traw, M. Brian; Bergelson, Joy
2003-01-01
Leaf trichomes protect plants from attack by insect herbivores and are often induced following damage. Hormonal regulation of this plant induction response has not been previously studied. In a series of experiments, we addressed the effects of artificial damage, jasmonic acid, salicylic acid, and gibberellin on induction of trichomes in Arabidopsis. Artificial damage and jasmonic acid caused significant increases in trichome production of leaves. The jar1-1 mutant exhibited normal trichome induction following treatment with jasmonic acid, suggesting that adenylation of jasmonic acid is not necessary. Salicylic acid had a negative effect on trichome production and consistently reduced the effect of jasmonic acid, suggesting negative cross-talk between the jasmonate and salicylate-dependent defense pathways. Interestingly, the effect of salicylic acid persisted in the nim1-1 mutant, suggesting that the Npr1/Nim1 gene is not downstream of salicylic acid in the negative regulation of trichome production. Last, we found that gibberellin and jasmonic acid had a synergistic effect on the induction of trichomes, suggesting important interactions between these two compounds. PMID:14551332
Caliendo, Angela M; Couturier, Marc R; Ginocchio, Christine C; Hanson, Kimberly E; Miller, Melissa B; Walker, Kimberly E; Frank, Gregory M
2016-07-15
In 2014, the US Food and Drug Administration (FDA) proposed to regulate laboratory-developed tests (LDTs)-diagnostics designed, manufactured, and used within a single laboratory. The Infectious Diseases Society of America, the American Society for Microbiology, and the Pan American Society for Clinical Virology recognize that the FDA is committed to protecting patients. However, our societies are concerned that the proposed regulations will limit access to testing and negatively impact infectious diseases (ID) LDTs. In this joint commentary, our societies discuss why LDTs are critical for ID patient care, hospital infection control, and public health responses. We also highlight how the FDA's proposed regulation of LDTs could impair patient access to life-saving tests and stifle innovation in ID diagnostics. Finally, our societies make specific recommendations for the FDA's consideration to reduce the burden of the proposed new rules on clinical laboratories and protect patients' access to state-of-the art, quality LDTs. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
Ye, Jing; Lenain, Christelle; Bauwens, Serge; Rizzo, Angela; Saint-Léger, Adelaïde; Poulet, Anaïs; Benarroch, Delphine; Magdinier, Frédérique; Morere, Julia; Amiard, Simon; Verhoeyen, Els; Britton, Sébastien; Calsou, Patrick; Salles, Bernard; Bizard, Anna; Nadal, Marc; Salvati, Erica; Sabatier, Laure; Wu, Yunlin; Biroccio, Annamaria; Londoño-Vallejo, Arturo; Giraud-Panis, Marie-Josèphe; Gilson, Eric
2010-07-23
Human telomeres are protected from DNA damage by a nucleoprotein complex that includes the repeat-binding factor TRF2. Here, we report that TRF2 regulates the 5' exonuclease activity of its binding partner, Apollo, a member of the metallo-beta-lactamase family that is required for telomere integrity during S phase. TRF2 and Apollo also suppress damage to engineered interstitial telomere repeat tracts that were inserted far away from chromosome ends. Genetic data indicate that DNA topoisomerase 2alpha acts in the same pathway of telomere protection as TRF2 and Apollo. Moreover, TRF2, which binds preferentially to positively supercoiled DNA substrates, together with Apollo, negatively regulates the amount of TOP1, TOP2alpha, and TOP2beta at telomeres. Our data are consistent with a model in which TRF2 and Apollo relieve topological stress during telomere replication. Our work also suggests that cellular senescence may be caused by topological problems that occur during the replication of the inner portion of telomeres. Copyright 2010 Elsevier Inc. All rights reserved.
Post-translational regulation of WRKY transcription factors in plant immunity.
Ishihama, Nobuaki; Yoshioka, Hirofumi
2012-08-01
Plants have evolved immune system to protect themselves against invading pathogens. Recent research has illustrated that signaling networks, after perception of diverse pathogen-derived signals, facilitate transcriptional reprogramming through mitogen-activated protein kinase (MAPK) cascades. WRKY proteins, which comprise a large family of plant transcription factors, are key players in plant immune responses. WRKY transcription factors participate in the control of defense-related genes either as positive or as negative regulators, and essentially are regulated at the transcriptional level. Emerging evidence emphasizes that group I WRKY transcription factors, which contain a conserved motif in the N-terminal region, are also activated by MAPK-dependent phosphorylation, underlining their importance in plant immunity. Copyright © 2012 Elsevier Ltd. All rights reserved.
Medical regulation of cognitive enhancement devices: some concerns
King, Mike; Gavaghan, Colin; McMillan, John
2014-01-01
The authors present a cogent and detailed case for altering the Medical Devices Directive to allow regulation of cognitive enhancement devices (CEDs). Protection against significant risk of harm, especially for the vulnerable, and promotion of benefit through informed use of CEDs are all good features of the proposal. However, the pre-market approval process has limitations, which we explore. We raise the possibility of ‘risk compensation’ in response to the introduction of safety measures, which could alter its effectiveness. The proposal alludes to use of ‘formally trained practitioners,’ which provide a further tier of regulation for CEDs within the proposal. We consider some positive and negative implications of this aspect of the proposal that might warrant further consideration. PMID:27774173
Maor-Nof, Maya; Romi, Erez; Sar Shalom, Hadas; Ulisse, Valeria; Raanan, Calanit; Nof, Aviv; Leshkowitz, Dena; Lang, Roland; Yaron, Avraham
2016-12-07
Developmental neuronal cell death and axonal elimination are controlled by transcriptional programs, of which their nature and the function of their components remain elusive. Here, we identified the dual specificity phosphatase Dusp16 as part of trophic deprivation-induced transcriptome in sensory neurons. Ablation of Dusp16 enhanced axonal degeneration in response to trophic withdrawal, suggesting that it has a protective function. Moreover, axonal skin innervation was severely reduced while neuronal elimination was increased in the Dusp16 knockout. Mechanistically, Dusp16 negatively regulates the transcription factor p53 and antagonizes the expression of the pro-degenerative factor, Puma (p53 upregulated modulator of apoptosis). Co-ablation of Puma with Dusp16 protected axons from rapid degeneration and specifically reversed axonal innervation loss early in development with no effect on neuronal deficits. Overall, these results reveal that physiological axonal elimination is regulated by a transcriptional program that integrates regressive and progressive elements and identify Dusp16 as a new axonal preserving factor. Copyright © 2016 Elsevier Inc. All rights reserved.
Release of VA Records Relating to HIV. Final rule.
2017-03-23
The Department of Veterans Affairs (VA) is amending its medical regulations governing the release of VA medical records. Specifically, VA is eliminating the restriction on sharing a negative test result for the human immunodeficiency virus (HIV) with veterans' outside providers. HIV testing is a common practice today in healthcare and the stigma of testing that may have been seen in the 1980s when HIV was first discovered is no longer prevalent. Continuing to protect negative HIV tests causes delays and an unnecessary burden on veterans when VA tries to share electronic medical information with the veterans' outside providers through electronic health information exchanges. For this same reason, VA will also eliminate restrictions on negative test results of sickle cell anemia. This final rule eliminates the current barriers to electronic medical information exchange.
Grant, Louise; Shearer, Kirsty D; Czopek, Alicja; Lees, Emma K; Owen, Carl; Agouni, Abdelali; Workman, James; Martin-Granados, Cristina; Forrester, John V; Wilson, Heather M; Mody, Nimesh; Delibegovic, Mirela
2014-02-01
Protein tyrosine phosphatase-1B (PTP1B) negatively regulates insulin and leptin signaling, rendering it an attractive drug target for treatment of obesity-induced insulin resistance. However, some studies suggest caution when targeting macrophage PTP1B, due to its potential anti-inflammatory role. We assessed the role of macrophage PTP1B in inflammation and whole-body metabolism using myeloid-cell (LysM) PTP1B knockout mice (LysM PTP1B). LysM PTP1B mice were protected against lipopolysaccharide (LPS)-induced endotoxemia and hepatic damage associated with decreased proinflammatory cytokine secretion in vivo. In vitro, LPS-treated LysM PTP1B bone marrow-derived macrophages (BMDMs) displayed increased interleukin (IL)-10 mRNA expression, with a concomitant decrease in TNF-α mRNA levels. These anti-inflammatory effects were associated with increased LPS- and IL-10-induced STAT3 phosphorylation in LysM PTP1B BMDMs. Chronic inflammation induced by high-fat (HF) feeding led to equally beneficial effects of macrophage PTP1B deficiency; LysM PTP1B mice exhibited improved glucose and insulin tolerance, protection against LPS-induced hyperinsulinemia, decreased macrophage infiltration into adipose tissue, and decreased liver damage. HF-fed LysM PTP1B mice had increased basal and LPS-induced IL-10 levels, associated with elevated STAT3 phosphorylation in splenic cells, IL-10 mRNA expression, and expansion of cells expressing myeloid markers. These increased IL-10 levels negatively correlated with circulating insulin and alanine transferase levels. Our studies implicate myeloid PTP1B in negative regulation of STAT3/IL-10-mediated signaling, highlighting its inhibition as a potential anti-inflammatory and antidiabetic target in obesity.
Ren, Xiang; Sun, Hong; Zhang, Chenghong; Li, Chen; Wang, Jinlei; Shen, Jie; Yu, Dong; Kong, Li
2016-07-01
The present study aimed to investigate the mechanisms that mediate the protective effects of pyridoxamine (PM) on light‑damaged retinal photoreceptor cells in diabetic mice. A high‑fat diet and streptozotocin were used to induce a mouse model of type II diabetes. During the experiment, mice were divided the mice into three types of group, as follows: Control groups (negative control and light‑damaged groups); experimental groups (diabetic and diabetic light‑damaged groups); and treatment groups (25, 50 and 100 mg/kg PM‑treated groups). Using hematoxylin‑eosin staining, the number of nuclear layer cells were counted. Western blotting and immunohistochemistry were performed to measure the levels of thioredoxin (Trx), phospho‑extracellular signal‑regulated kinase 1/2 (p‑Erk1/2), nuclear factor erythroid 2‑related factor 2 (Nrf2) and apoptosis signal‑regulating kinase 1 (ASK1). The photoreceptor cell count in the outer nuclear layer of the light‑damaged, diabetic control and diabetic light‑damaged groups were significantly reduced compared with the negative control group (P<0.001). The cell counts in the PM‑treated groups were significantly increased compared with the diabetic group (P<0.001). Compared with the negative control group, the light‑damaged, diabetic and diabetic light‑damaged groups exhibited significantly decreased Trx, p‑Erk1/2 and Nrf2 expression levels (P<0.001), and significantly increased ASK1 expression levels (P<0.001). However, in the PM‑treated groups, Trx, p‑Erk1/2 and Nrf2 expression levels were significantly increased (P<0.001), and ASK1 expression was significantly decreased (P<0.001). The results of the present study demonstrate that PM protects retinal photoreceptor cells against light damage in diabetic mice, and that its mechanism may be associated with the upregulation of Trx, p‑Erk1/2 and Nrf2 expression, and the downregulation of ASK1 expression.
NASA Astrophysics Data System (ADS)
Missall, S.; Welp, M.; Thevs, N.; Abliz, A.; Halik, Ü.
2015-06-01
The city of Aksu, situated at the northern fringe of the Taklimakan Desert in northwest China, is exposed to severe periodic dust and sand storms. In 1986, local authorities decided to establish a peri-urban shelterbelt plantation, the so-called Kökyar Protection Forest, with the aim of reducing dust and sand storm impacts on Aksu City by the regulating ecosystem services provided by the plantation. It was realised as a patchwork of poplar shelterbelts and orchards. The total area of the plantation reached 3800 ha in 2005. The Kökyar Protection Forest is used as a case study to answer the following question: under which institutional frameworks and to which financial conditions can peri-urban shelterbelts be established and maintained? The endeavour of planting the shelterbelt was made possible by the annual mass mobilisation of Aksu citizens, based on the Chinese regulation of the "National Compulsory Afforestation Campaigns". Establishment costs amounted to ca. CNY 60 000 ha-1 (ca. USD 10 000 ha-1). Permanent maintenance of the plantation is facilitated by leasing orchard plots to private fruit farmers. From the perspective of the local economy, annual farming net benefits generated by Kökyar fruit farmers more than compensate for annual government grants for maintenance, resulting in an average overall monetary net benefit of at least CNY 10 500 ha-1 (ca. USD 1600 ha-1) in the long term. For a more complete understanding of Kökyar Protection Forest, future research should be directed towards quantifying the effect of its regulating ecosystem services and on investigating the negative downstream consequences of its water consumption.
Adaptive disengagement buffers self-esteem from negative social feedback.
Leitner, Jordan B; Hehman, Eric; Deegan, Matthew P; Jones, James M
2014-11-01
The degree to which self-esteem hinges on feedback in a domain is known as a contingency of self-worth, or engagement. Although previous research has conceptualized engagement as stable, it would be advantageous for individuals to dynamically regulate engagement. The current research examined whether the tendency to disengage from negative feedback accounts for variability in self-esteem. We created the Adaptive Disengagement Scale (ADS) to capture individual differences in the tendency to disengage self-esteem from negative outcomes. Results demonstrated that the ADS is reliable and valid (Studies 1 and 2). Furthermore, in response to negative social feedback, higher scores on the ADS predicted greater state self-esteem (Study 3), and this relationship was mediated by disengagement (Study 4). These findings demonstrate that adaptive disengagement protects self-esteem from negative outcomes and that the ADS is a valid measure of individual differences in the implementation of this process. © 2014 by the Society for Personality and Social Psychology, Inc.
Scrimin, Sara; Moscardino, Ughetta; Mason, Lucia
2018-06-11
Children's ability to remain focused on a task despite the presence of emotionally salient distractors in the environment is crucial for successful learning and academic performance. This study investigated first-graders' allocation of attentional resources in the presence of distracting emotional, school-related social interaction stimuli. Moreover, we examined whether such attentional processes were influenced by students' self-regulation, as indexed by heart period variability, observed classroom climate, or their interaction. Seventy-two-first graders took part in the study. To assess allocation of attentional resources, students' reaction times on an emotional Stroop task were registered by recording response times to colour frames placed around pictures of distracting emotional, school-related social interaction stimuli (i.e., emotional interference index). Moreover, heart period variability was measured by recording children's electrocardiogram at rest during an individual session, whereas classroom climate was observed during class activities by a trained researcher. Images representing negative social interactions required greater attentional resources than images depicting positive ones. Heart period variability and classroom climate were each significantly and independently associated with the emotional interference index. A significant interaction also emerged, indicating that among children experiencing a negative classroom climate, those who had a higher basal heart period variability (higher self-regulation) were less distracted by negative emotional material and remained more focused on a task compared to those with lower heart period variability (lower self-regulation). Negative interactions require greater attentional resources than positive scenes. Moreover, with a negative classroom climate, higher basal heart period variability is a protective factor. Implications for theory and practice are discussed. © 2018 The British Psychological Society.
The iron chelator deferasirox synergizes with chemotherapy to treat triple negative breast cancers.
Tury, Sandrine; Assayag, Franck; Bonin, Florian; Chateau-Joubert, Sophie; Servely, Jean-Luc; Vacher, Sophie; Becette, Véronique; Caly, Martial; Rapinat, Audrey; Gentien, David; de la Grange, Pierre; Schnitzler, Anne; Lallemand, François; Marangoni, Elisabetta; Bièche, Ivan; Callens, Céline
2018-06-07
To ensure their high proliferation rate, tumor cells display an iron metabolic disorder with increased iron needs, making them more susceptible to iron deprivation. This vulnerability could be a therapeutic target. In breast cancers, the development of new therapeutic approaches is urgently needed for patients with triple negative tumors which frequently relapse after chemotherapy and suffer from a lack of targeted therapies. In this work, we demonstrated that deferasirox (DFX) synergizes with standard chemotherapeutic agents such as with doxorubicin, cisplatin and carboplatin to inhibit cell proliferation and induce apoptosis and autophagy in triple-negative breast cancer (TNBC) cell lines. Moreover, the combination of DFX with doxorubicin and cyclophosphamide delayed recurrences in breast cancer patient-derived xenografts without increasing the side-effects of chemotherapies alone or altering global iron storage of mice. Antitumor synergy of DFX and doxorubicin seems to involve down-regulation of the PI3K and NF-κB pathways. Iron deprivation in combination with chemotherapy could thus help to improve the effectiveness of chemotherapy in TNBC patients without increasing toxicities. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Impacts of marine protected areas on fishing communities.
Mascia, Michael B; Claus, C Anne; Naidoo, Robin
2010-10-01
Marine protected areas (MPAs) are a popular conservation strategy, but their impacts on human welfare are poorly understood. To inform future research and policy decisions, we reviewed the scientific literature to assess MPA impacts on five indicators of human welfare: food security, resource rights, employment, community organization, and income. Following MPA establishment, food security generally remained stable or increased in older and smaller MPAs. The ability of most fishing groups to govern MPA resources changed. Increased resource rights were positively correlated with MPA zoning and compliance with MPA regulations. Small sample sizes precluded statistical tests of the impacts of MPAs on employment, community organization, and income. Our results demonstrate that MPAs shape the social well-being and political power of fishing communities; impacts (positive and negative) vary within and among social groups; and social impacts are correlated with some--but not all--commonly hypothesized explanatory factors. Accordingly, MPAs may represent a viable strategy for enhancing food security and empowering local communities, but current practices negatively affect at least a minority of fishers. To inform policy making, further research must better document and explain variation in the positive and negative social impacts of MPAs. © 2010 Society for Conservation Biology.
FANCD2 protects against bone marrow injury from ferroptosis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Song, Xinxin; Xie, Yangchun; Kang, Rui
Bone marrow injury remains a serious concern in traditional cancer treatment. Ferroptosis is an iron- and oxidative-dependent form of regulated cell death that has become part of an emerging strategy for chemotherapy. However, the key regulator of ferroptosis in bone marrow injury remains unknown. Here, we show that Fanconi anemia complementation group D2 (FANCD2), a nuclear protein involved in DNA damage repair, protects against ferroptosis-mediated injury in bone marrow stromal cells (BMSCs). The classical ferroptosis inducer erastin remarkably increased the levels of monoubiquitinated FANCD2, which in turn limited DNA damage in BMSCs. FANCD2-deficient BMSCs were more sensitive to erastin-induced ferroptosismore » (but not autophagy) than FANCD2 wild-type cells. Knockout of FANCD2 increased ferroptosis-associated biochemical events (e.g., ferrous iron accumulation, glutathione depletion, and malondialdehyde production). Mechanically, FANCD2 regulated genes and/or expression of proteins involved in iron metabolism (e.g., FTH1, TF, TFRC, HAMP, HSPB1, SLC40A1, and STEAP3) and lipid peroxidation (e.g., GPX4). Collectively, these findings indicate that FANCD2 plays a novel role in the negative regulation of ferroptosis. FANCD2 could represent an amenable target for the development of novel anticancer therapies aiming to reduce the side effects of ferroptosis inducers.« less
Laouar, Yasmina; Sutterwala, Fayyaz S; Gorelik, Leonid; Flavell, Richard A
2005-06-01
Interferon-gamma and interleukin 12 produced by the innate arm of the immune system are important regulators of T helper type 1 (T(H)1) cell development, but signals that negatively regulate their expression remain controversial. Here we show that transforming growth factor-beta (TGF-beta) controlled T(H)1 differentiation through the regulation of interferon-gamma produced by natural killer (NK) cells. Blockade of TGF-beta signaling in NK cells caused the accumulation of a large pool of NK cells secreting copious interferon-gamma, responsible for T(H)1 differentiation and protection from leishmania infection. In contrast, blockade of TGF-beta signaling in dendritic cells did not affect dendritic cell homeostasis or interleukin 12 production, thus indicating a previously undescribed demarcation of the function of TGF-beta in NK cells versus dendritic cells.
Protecting the people?: risk communication and the chequered history and performance of bureaucracy.
Hugman, Bruce
2012-11-01
The history and characteristics of bureaucracy1 are examined with a view to understanding the impact of the bureaucratic mindset on medicines' regulation, the pharmaceutical industry and healthcare delivery with a focus on risk communication, pharmacovigilance and patient safety. Controversies and allegations relating to common, negative effects of bureaucratic regulatory and management systems are reviewed and examples of creative and effective practice provided. Strategic directions and specific actions for reform are proposed.2.
Endothelial-specific inhibition of NF-κB enhances functional haematopoiesis.
Poulos, Michael G; Ramalingam, Pradeep; Gutkin, Michael C; Kleppe, Maria; Ginsberg, Michael; Crowley, Michael J P; Elemento, Olivier; Levine, Ross L; Rafii, Shahin; Kitajewski, Jan; Greenblatt, Matthew B; Shim, Jae-Hyuck; Butler, Jason M
2016-12-21
Haematopoietic stem cells (HSCs) reside in distinct niches within the bone marrow (BM) microenvironment, comprised of endothelial cells (ECs) and tightly associated perivascular constituents that regulate haematopoiesis through the expression of paracrine factors. Here we report that the canonical NF-κB pathway in the BM vascular niche is a critical signalling axis that regulates HSC function at steady state and following myelosuppressive insult, in which inhibition of EC NF-κB promotes improved HSC function and pan-haematopoietic recovery. Mice expressing an endothelial-specific dominant negative IκBα cassette under the Tie2 promoter display a marked increase in HSC activity and self-renewal, while promoting the accelerated recovery of haematopoiesis following myelosuppression, in part through protection of the BM microenvironment following radiation and chemotherapeutic-induced insult. Moreover, transplantation of NF-κB-inhibited BM ECs enhanced haematopoietic recovery and protected mice from pancytopenia-induced death. These findings pave the way for development of niche-specific cellular approaches for the treatment of haematological disorders requiring myelosuppressive regimens.
Endothelial-specific inhibition of NF-κB enhances functional haematopoiesis
Poulos, Michael G.; Ramalingam, Pradeep; Gutkin, Michael C.; Kleppe, Maria; Ginsberg, Michael; Crowley, Michael J. P.; Elemento, Olivier; Levine, Ross L.; Rafii, Shahin; Kitajewski, Jan; Greenblatt, Matthew B.; Shim, Jae-Hyuck; Butler, Jason M.
2016-01-01
Haematopoietic stem cells (HSCs) reside in distinct niches within the bone marrow (BM) microenvironment, comprised of endothelial cells (ECs) and tightly associated perivascular constituents that regulate haematopoiesis through the expression of paracrine factors. Here we report that the canonical NF-κB pathway in the BM vascular niche is a critical signalling axis that regulates HSC function at steady state and following myelosuppressive insult, in which inhibition of EC NF-κB promotes improved HSC function and pan-haematopoietic recovery. Mice expressing an endothelial-specific dominant negative IκBα cassette under the Tie2 promoter display a marked increase in HSC activity and self-renewal, while promoting the accelerated recovery of haematopoiesis following myelosuppression, in part through protection of the BM microenvironment following radiation and chemotherapeutic-induced insult. Moreover, transplantation of NF-κB-inhibited BM ECs enhanced haematopoietic recovery and protected mice from pancytopenia-induced death. These findings pave the way for development of niche-specific cellular approaches for the treatment of haematological disorders requiring myelosuppressive regimens. PMID:28000664
Liu, Ke; Jing, Ying; Zhang, Wen; Fu, Xuejie; Zhao, Huan; Zhou, Xichao; Tao, Yunxia; Yang, Huilin; Zhang, Yan; Zen, Ke; Zhang, Chenyu; Li, Donghai; Shi, Qin
2017-04-01
Osteoporosis is a serious health problem worldwide. MicroRNA is a post-transcriptional regulator of gene expression by either promoting mRNA degradation or interfering with mRNA translation of specific target genes. It plays a significant role in the pathogenesis of osteoporosis. Here, we first demonstrated that miR-106b (miR-106b-5p) negatively regulated osteogenic differentiation of mesenchymal stem cells in vitro. Then, we found that miR-106b expression increased in C57BL/6 mice with glucocorticoid-induced osteoporosis (GIOP), and that silencing of miR-106b signaling protected mice against GIOP through promoting bone formation and inhibiting bone resorption. At last, we showed that miR-106b inhibited osteoblastic differentiation and bone formation partly through directly targeting bone morphogenetic protein 2 (BMP2) both in vitro and in the GIOP model. Together, our findings have identified the role and mechanism of miR-106b in negatively regulating osteogenesis. Inhibition of miR-106b might be a potential new strategy for treating osteoporosis and bone defects. Copyright © 2017. Published by Elsevier Inc.
Williams, Pete A; Braine, Catherine E; Foxworth, Nicole E; Cochran, Kelly E; John, Simon W M
2017-04-26
We previously reported a profound long-term neuroprotection subsequent to a single radiation-therapy in the DBA/2J mouse model of glaucoma. This neuroprotection prevents entry of monocyte-like immune cells into the optic nerve head during glaucoma. Gene expression studies in radiation-treated mice implicated Glycam1 in this protection. Glycam1 encodes a proteoglycan ligand for L-selectin and is an excellent candidate to modulate immune cell entry into the eye. Here, we experimentally test the hypothesis that radiation-induced over-expression of Glycam1 is a key component of the neuroprotection. We generated a null allele of Glycam1 on a DBA/2J background. Gene and protein expression of Glycam1, monocyte entry into the optic nerve head, retinal ganglion cell death, and axon loss in the optic nerve were assessed. Radiation therapy potently inhibits monocyte entry into the optic nerve head and prevents retinal ganglion cell death and axon loss. DBA/2J mice carrying a null allele of Glycam1 show increased monocyte entry and increased retinal ganglion cell death and axon loss following radiation therapy, but the majority of optic nerves were still protected by radiation therapy. Although GlyCAM1 is an L-selectin ligand, its roles in immunity are not yet fully defined. The current study demonstrates a partial role for GlyCAM1 in radiation-mediated protection. Furthermore, our results clearly show that GlyCAM1 levels modulate immune cell entry from the vasculature into neural tissues. As Glycam1 deficiency has a more profound effect on cell entry than on neurodegeneration, further experiments are needed to precisely define the role of monocyte entry in DBA/2J glaucoma. Nevertheless, GlyCAM1's function as a negative regulator of extravasation may lead to novel therapeutic strategies for an array of common conditions involving inflammation.
Cultural differences in hedonic emotion regulation after a negative event.
Miyamoto, Yuri; Ma, Xiaoming; Petermann, Amelia G
2014-08-01
Beliefs about emotions can influence how people regulate their emotions. The present research examined whether Eastern dialectical beliefs about negative emotions lead to cultural differences in how people regulate their emotions after experiencing a negative event. We hypothesized that, because of dialectical beliefs about negative emotions prevalent in Eastern culture, Easterners are less motivated than Westerners to engage in hedonic emotion regulation-up-regulation of positive emotions and down-regulation of negative emotions. By assessing online reactions to a recent negative event, Study 1 found that European Americans are more motivated to engage in hedonic emotion regulation. Furthermore, consistent with the reported motivation to regulate emotion hedonically, European Americans show a steeper decline in negative emotions 1 day later than do Asians. By examining retrospective memory of reactions to a past negative event, Study 2 further showed that cultural differences in hedonic emotion regulation are mediated by cultural differences in dialectical beliefs about motivational and cognitive utility of negative emotions, but not by personal deservingness or self-efficacy beliefs. These findings demonstrate the role of cultural beliefs in shaping emotion regulation and emotional experiences.
Suppression of MicroRNA let-7a Expression by Agmatine Regulates Neural Stem Cell Differentiation
Song, Juhyun; Oh, Yumi; Kim, Jong Youl; Cho, Kyoung Joo
2016-01-01
Purpose Neural stem cells (NSCs) effectively reverse some severe central nervous system (CNS) disorders, due to their ability to differentiate into neurons. Agmatine, a biogenic amine, has cellular protective effects and contributes to cellular proliferation and differentiation in the CNS. Recent studies have elucidated the function of microRNA let-7a (let-7a) as a regulator of cell differentiation with roles in regulating genes associated with CNS neurogenesis. Materials and Methods This study aimed to investigate whether agmatine modulates the expression of crucial regulators of NSC differentiation including DCX, TLX, c-Myc, and ERK by controlling let-7a expression. Results Our data suggest that high levels of let-7a promoted the expression of TLX and c-Myc, as well as repressed DCX and ERK expression. In addition, agmatine attenuated expression of TLX and increased expression of ERK by negatively regulating let-7a. Conclusion Our study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders. PMID:27593875
Suppression of MicroRNA let-7a Expression by Agmatine Regulates Neural Stem Cell Differentiation.
Song, Juhyun; Oh, Yumi; Kim, Jong Youl; Cho, Kyoung Joo; Lee, Jong Eun
2016-11-01
Neural stem cells (NSCs) effectively reverse some severe central nervous system (CNS) disorders, due to their ability to differentiate into neurons. Agmatine, a biogenic amine, has cellular protective effects and contributes to cellular proliferation and differentiation in the CNS. Recent studies have elucidated the function of microRNA let-7a (let-7a) as a regulator of cell differentiation with roles in regulating genes associated with CNS neurogenesis. This study aimed to investigate whether agmatine modulates the expression of crucial regulators of NSC differentiation including DCX, TLX, c-Myc, and ERK by controlling let-7a expression. Our data suggest that high levels of let-7a promoted the expression of TLX and c-Myc, as well as repressed DCX and ERK expression. In addition, agmatine attenuated expression of TLX and increased expression of ERK by negatively regulating let-7a. Our study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders.
Lynch, Kellie R; Renzetti, Claire M
2017-05-01
Research suggests that the relationship between alcohol use and intimate partner violence (IPV) is moderated by a range of other factors. Therefore, we investigated the relationship between alcohol use, hostile sexism, and religious self-regulation with perpetration. Using a national sample of 255 men, we found that hostile sexism was associated with physical violence toward a partner and alcohol use was positively associated with psychological abuse toward a partner. With regard to religious self-regulation, we found that introjected religious self-regulation was positively associated with hostile sexism and positively associated with perpetrating physical IPV. Identified religious self-regulation was negatively associated with physical violence perpetration. We also found significant interactions among our independent measures on physical IPV perpetration. These analyses suggest that increased alcohol consumption elevates the risk for physical violence perpetration among men who are high in introjected religious self-regulation and low in hostile sexism, while reducing the risk for perpetration in men who are high in identified religious self-regulation and low in hostile sexism. Implications and limitations of the findings are discussed.
Li, Qi; Chen, Xi; Kan, Xiao-Xi; Li, Yu-Jie; Yang, Qing; Wang, Ya-Jie; Chen, Ying; Weng, Xiao-Gang; Cai, Wei-Yan; Huang, He-Fei; Zhu, Xiao-Xin
2016-02-01
To reveal the protective and anti-apoptosis effect of compound Ginkgo biloba granules on oxidative stress injury of human umbilical vein endothelial cells (HUVEC). Negative control group, H2O2 model group and 4 drug pretreatment groups (80, 160, 320, 640 mg• L⁻¹) were established. The cell proliferation, morphological changes in each group after oxidative stress injury was detected by MTT assay and through microscope observation respectively. The content of LDH, MDA, SOD and NO and SOD activity in supernatant were detected to judge the protection effect of the drugs on endothelial cells. The protective effect on HUVEC apoptosis was analyzed by Caspase-3 activity test and Annexin V-FITC/PI staining. Western blot was used to observe the expression of apoptosis-related proteins Bcl-2 and Bax. Results showed that 1 200 μmol• L⁻¹ H2O2 can induce oxidative stress injury in endothelial cells and reduce the cell survival rate; cell proliferation inhibition degree is positively correlated with the effect time of H2O2. Besides, 80, 160, 320 640 mg•L⁻¹ compound Ginkgo biloba granules can protect HUVEC from oxidative stress injury, recover the normal proliferation level of cells, improve their state, prohibit cell apoptosis, and can up-regulate and down-regulate the expression level of Bcl-2 and Bax respectively. In conclusion, compound G. biloba granules can protect HUVEC from the oxidative stress injury induced by H2O2, its mechanism may be correlated with inhibition of the mitochondrial apoptotic pathway in HUVEC. Copyright© by the Chinese Pharmaceutical Association.
[Various aspects of public health system development under market economy].
Polyakov, I V; Uvarov, S A
1995-01-01
Transfer from administrative methods of management to economic relationships in the public health system leads to reevaluation of the regularities in the development of the system of population health protection under conditions of marketing relations. The paper presents the logistic aspects of public health management under new conditions: positive and negative features in the development of medical insurance and offers a concept of introduction of a system of synchronous regulation of material, financial, and information streams in public health.
Coping with Self-Threat and the Evaluation of Self-Related Traits: An fMRI Study
Corcoran, Katja; Ebner, Franz
2015-01-01
A positive view of oneself is important for a healthy lifestyle. Self-protection mechanisms such as suppressing negative self-related information help us to maintain a positive view of ourselves. This is of special relevance when, for instance, a negative test result threatens our positive self-view. To date, it is not clear which brain areas support self-protective mechanisms under self-threat. In the present functional magnetic resonance imaging (fMRI) study the participants (N = 46) received a (negative vs. positive) performance test feedback before entering the scanner. In the scanner, the participants were instructed to ascribe personality traits either to themselves or to a famous other. Our results showed that participants responded slower to negative self-related traits compared to positive self-related traits. High self-esteem individuals responded slower to negative traits compared to low self-esteem individuals following a self-threat. This indicates that high self-esteem individuals engage more in self-enhancing strategies after a threat by inhibiting negative self-related information more successfully than low self-esteem individuals. This behavioral pattern was mirrored in the fMRI data as dACC correlated positively with trait self-esteem. Generally, ACC activation was attenuated under threat when participants evaluated self-relevant traits and even more for negative self-related traits. We also found that activation in the ACC was negatively correlated with response times, indicating that greater activation of the ACC is linked to better access (faster response) to positive self-related traits and to impaired access (slower response) to negative self-related traits. These results confirm the ACC function as important in managing threatened self-worth but indicate differences in trait self-esteem levels. The fMRI analyses also revealed a decrease in activation within the left Hippocampus and the right thalamus under threat. This indicates that a down-regulation of activation in these regions might also serve as coping mechanism in dealing with self-threat. PMID:26333130
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gorgani-Firuzjaee, Sattar; Adeli, Khosrow; Meshkani, Reza, E-mail: rmeshkani@tums.ac.ir
The serine–threonine kinase Akt regulates proliferation and survival by phosphorylating a network of protein substrates; however, the role of a negative regulator of the Akt pathway, the SH2-domain-containing inositol 5-phosphatase (SHIP2) in apoptosis of the hepatocytes, remains unknown. In the present study, we studied the molecular mechanisms linking SHIP2 expression to apoptosis using overexpression or suppression of SHIP2 gene in HepG2 cells exposed to palmitate (0.5 mM). Overexpression of the dominant negative mutant SHIP2 (SHIP2-DN) significantly reduced palmitate-induced apoptosis in HepG2 cells, as these cells had increased cell viability, decreased apoptotic cell death and reduced the activity of caspase-3, cytochrome cmore » and poly (ADP-ribose) polymerase. Overexpression of the wild-type SHIP2 gene led to a massive apoptosis in HepG2 cells. The protection from palmitate-induced apoptosis by SHIP2 inhibition was accompanied by a decrease in the generation of reactive oxygen species (ROS). In addition, SHIP2 inhibition was accompanied by an increased Akt and FOXO-1 phosphorylation, whereas overexpression of the wild-type SHIP2 gene had the opposite effects. Taken together, these findings suggest that SHIP2 expression level is an important determinant of hepatic lipoapotosis and its inhibition can potentially be a target in treatment of hepatic lipoapoptosis in diabetic patients. - Highlights: • Lipoapoptosis is the major contributor to the development of NAFLD. • The PI3-K/Akt pathway regulates apoptosis in different cells. • The role of negative regulator of this pathway, SHIP2 in lipoapoptosis is unknown. • SHIP2 inhibition significantly reduces palmitate-induced apoptosis in HepG2 cells. • SHIP2 inhibition prevents palmitate induced-apoptosis by regulating Akt/FOXO1 pathway.« less
40 CFR 62.2400 - Identification of plan-negative declaration.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 8 2011-07-01 2011-07-01 false Identification of plan-negative declaration. 62.2400 Section 62.2400 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR....2400 Identification of plan—negative declaration. Letter from Florida Department of Environmental...
Patock-Peckham, J A; Cheong, J; Balhorn, M E; Nagoshi, C T
2001-09-01
This investigation sought to determine how different parenting styles are related to general self-regulatory processes that are linked to alcohol use and abuse. Self-regulation and, more specifically, thoughts of control over drinking are forms of positive self-control mechanisms. Parenting styles are known determinants of both negative and positive self-control mechanisms in offspring. According to social learning theory, stronger relationships between parenting style and self-regulatory processes would be expected from the parent who is the same sex as the respondent. A total of 144 female and 107 male college students currently using alcohol were administered a questionnaire on their alcohol use and problems, perceived style of parenting (authoritarian, permissive, or authoritative) of their parents, self-regulation, and perceived control of drinking. A model linking parenting styles, self-regulatory processes, and control over drinking with alcohol use and alcohol problems was tested across sex groups by using structural equation modeling. In general, the parenting style of the parent of the same sex as the respondent's was found to be significantly related to self-regulation, which is known to be protective against alcohol use and abuse. A permissive parent of the same sex as the respondent was negatively associated with good self-regulatory processes for both men and women. Having an authoritative mother was also shown to be related to higher levels of self-regulation for women. Self-regulation mediated the pathway from a permissive parenting style to perceived drinking control, which, in turn, mediated the pathway from self-regulation to alcohol use and problems. Finally, self-regulation mediated the positive pathway from an authoritative mother to perceived control over drinking for women.
Yu, Cheng-Rong; Kim, Sung-Hye; Mahdi, Rashid M.; Egwuagu, Charles E.
2013-01-01
Suppressors of cytokine signaling (SOCS) proteins are negative-feedback regulators of JAK/STAT pathway and SOCS3 contributes to host immunity by regulating the intensity/duration of cytokine signals and inflammatory responses. Mice with Socs3 deletion in myeloid cells exhibit enhanced STAT3-signaling, expansion of Th1 and Th17 cells and developed severe experimental autoimmune encephalomyelitis (EAE). Interestingly, development of the unique IL-17/IFN-γ-double producing (Th17/IFN-γ and Tc17/IFN-γ) subsets that exhibit strong cytotoxic activities and associated with pathogenesis of several autoimmune diseases, has recently been shown to depend on epigenetic suppression of SOCS3 expression, further suggesting involvement of SOCS3 in autoimmunity and tumor immunity. In this study, we generated mice with Socs3 deletion in CD4 T cell compartment (CD4-SOCS3KO) to determine in vivo effects of the loss of Socs3 in the T cell-mediated autoimmune disease, experimental autoimmune uveitis (EAU). In contrast to the exacerbation of EAE in myeloid-specific SOCS3-deleted mice, CD4-SOCS3KO mice were protected from acute and chronic uveitis. Protection from EAU correlated with enhanced expression of CTLA4 and expansion of IL-10 producing Tregs with augmented suppressive activities. We further show that SOCS3 interacts with CTLA4 and negatively regulates CTLA4 levels in T cells, providing mechanistic explanation for the expansion of Tregs in CD4-SOCS3 during EAU. Contrary to in vitro epigenetic studies, Th17/IFN-γ and Tc17/IFN-γ populations were markedly reduced in CD4-SOCS3KO, suggesting that SOCS3 promotes expansion of Th17/IFN-γ subset associated with development of severe uveitis. Thus, SOCS3 is a potential therapeutic target in uveitis and other auto-inflammatory diseases. PMID:24101549
Growth in Adolescent Self-Regulation and Impact on Sexual Risk-Taking: A Curve-of-Factors Analysis.
Crandall, AliceAnn; Magnusson, Brianna M; Novilla, M Lelinneth B
2018-04-01
Adolescent self-regulation is increasingly seen as an important predictor of sexual risk-taking behaviors, but little is understood about how changes in self-regulation affect later sexual risk-taking. Family financial stress may affect the development of self-regulation and later engagement in sexual risk-taking. We examined whether family financial stress influences self-regulation in early adolescence (age 13) and growth in self-regulation throughout adolescence (from age 13-17 years). We then assessed the effects of family financial stress, baseline self-regulation, and the development of self-regulation on adolescent sexual risk-taking behaviors at age 18 years. Using a curve-of-factors model, we examined these relationships in a 6-year longitudinal study of 470 adolescents (52% female) and their parents from a large northwestern city in the United States. Results indicated that family financial stress was negatively associated with baseline self-regulation but not with growth in self-regulation throughout adolescence. Both baseline self-regulation and growth in self-regulation were predictive of decreased likelihood of engaging in sexual risk-taking. Family financial stress was not predictive of later sexual risk-taking. Intervening to support the development of self-regulation in adolescence may be especially protective against later sexual risk-taking.
Shimazu, Tomoyuki; Villena, Julio; Tohno, Masanori; Fujie, Hitomi; Hosoya, Shoichi; Shimosato, Takeshi; Aso, Hisashi; Suda, Yoshihito; Kawai, Yasushi; Saito, Tadao; Makino, Seiya; Ikegami, Shuji; Itoh, Hiroyuki
2012-01-01
The effect of Lactobacillus jensenii TL2937 on the inflammatory immune response triggered by enterotoxigenic Escherichia coli (ETEC) and lipopolysaccharide (LPS) in a porcine intestinal epitheliocyte cell line (PIE cells) was evaluated. Challenges with ETEC or LPS elicited Toll-like receptor 4 (TLR4)-mediated inflammatory responses in cultured PIE cells, indicating that our cell line may be useful for studying inflammation in the guts of weaning piglets. In addition, we demonstrated that L. jensenii TL2937 attenuated the expression of proinflammatory cytokines and chemokines caused by ETEC or LPS challenge by downregulating TLR4-dependent nuclear factorκB (NF-κB) and mitogen-activated protein kinase (MAPK) activation. Furthermore, we demonstrated that L. jensenii TL2937 stimulation of PIE cells upregulated three negative regulators of TLRs: A20, Bcl-3, and MKP-1, deepening the understanding of an immunobiotic mechanism of action. L. jensenii TL2937-mediated induction of negative regulators of TLRs would have a substantial physiological impact on homeostasis in PIE cells, because excessive TLR inflammatory signaling would be downregulated. These results indicated that PIE cells can be used to study the mechanisms involved in the protective activity of immunobiotics against intestinal inflammatory damage and may provide useful information for the development of new immunologically functional feeds that help to prevent inflammatory intestinal disorders, including weaning-associated intestinal inflammation. PMID:22083706
Hegerle, N; Bose, J; Ramachandran, G; Galen, J E; Levine, M M; Simon, R; Tennant, S M
2018-03-30
O-polysaccharide (OPS) molecules are protective antigens for several bacterial pathogens, and have broad utility as components of glycoconjugate vaccines. Variability in the OPS chain length is one obstacle towards further development of these vaccines. Introduction of sizing steps during purification of OPS molecules of suboptimal or of mixed lengths introduces additional costs and complexity while decreasing the final yield. The overall goal of this study was to demonstrate the utility of engineering Gram-negative bacteria to produce homogenous O-polysaccharide populations that can be used as the basis of carbohydrate vaccines by overexpressing O-polysaccharide chain length regulators of the Wzx-/Wzy-dependent pathway. The O-polysaccharide chain length regulators wzzB and fepE from Salmonella Typhimurium I77 and wzz2 from Pseudomonas aeruginosa PAO1 were cloned and expressed in the homologous organism or in other Gram-negative bacteria. Overexpression of these Wzz proteins in the homologous organism significantly increased the proportion of long or very long chain O-polysaccharides. The same observation was made when wzzB was overexpressed in Salmonella Paratyphi A and Shigella flexneri, and wzz2 was overexpressed in two other strains of P. aeruginosa. Overexpression of Wzz proteins in Gram-negative bacteria using the Wzx/Wzy-dependant pathway for lipopolysaccharide synthesis provides a genetic method to increase the production of an O-polysaccharide population of a defined size. The methods presented herein represent a cost-effective and improved strategy for isolating preferred OPS vaccine haptens, and could facilitate the further use of O-polysaccharides in glycoconjugate vaccine development. © 2018 The Society for Applied Microbiology.
The zinc fingers of the Small Optic Lobes (SOL) calpain bind polyubiquitin.
Hastings, Margaret H; Qiu, Alvin; Zha, Congyao; Farah, Carole A; Mahdid, Yacine; Ferguson, Larissa; Sossin, Wayne S
2018-05-28
The Small Optic Lobes (SOL) calpain is a highly conserved member of the calpain family expressed in the nervous system. A dominant negative form of the SOL calpain inhibited consolidation of one form of synaptic plasticity, non-associative facilitation, in sensory-motor neuronal cultures in Aplysia, presumably by inhibiting cleavage of protein kinase Cs (PKCs) into constitutively active protein kinase Ms (PKMs) (Hu et al, 2017a). SOL calpains have a conserved set of 5-6 N-terminal zinc fingers. Bioinformatic analysis suggests that these zinc fingers could bind to ubiquitin. In this study, we show that both the Aplysia and mouse SOL calpain (also known as Calpain 15) zinc fingers bind ubiquitinated proteins, and we confirm that Aplysia SOL binds poly- but not mono or di-ubiquitin. No specific zinc finger is required for polyubiquitin binding. Neither polyubiquitin nor calcium was sufficient to induce purified Aplysia SOL calpain to autolyse or to cleave the atypical PKC to PKM in vitro. In Aplysia, overexpression of the atypical PKC in sensory neurons leads to an activity-dependent cleavage event and an increase in nuclear ubiquitin staining. Activity-dependent cleavage is partially blocked by a dominant negative SOL calpain, but not by a dominant negative classical calpain. The cleaved PKM was stabilized by the dominant negative classical calpain and destabilized by a dominant negative form of the PKM stabilizing proteinKIdney/BRAin protein(KIBRA). These studies provide new insight into SOL calpain's function and regulation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Paerewijck, Oonagh; Maertens, Brecht; Dreesen, Leentje; Van Meulder, Frederik; Peelaers, Iris; Ratman, Dariusz; Li, Robert W; Lubberts, Erik; De Bosscher, Karolien; Geldhof, Peter
2017-08-17
The protozoan parasite Giardia is a highly prevalent intestinal pathogen with a wide host range. Data obtained in mice, cattle and humans revealed the importance of IL-17A in the development of a protective immune response against Giardia. The aim of this study was to further unravel the protective effector mechanisms triggered by IL-17A following G. muris infection in mice, by an RNA-sequencing approach. C57BL/6 WT and C57BL/6 IL-17RA KO mice were orally infected with G. muris cysts. Three weeks post infection, intestinal tissue samples were collected for RNA-sequencing, with samples from uninfected C57BL/6 WT and C57BL/6 IL-17RA KO animals serving as negative controls. Differential expression analysis showed that G. muris infection evoked the transcriptional upregulation of a wide array of genes, mainly in animals with competent IL-17RA signaling. IL-17RA signaling induced the production of various antimicrobial peptides, such as angiogenin 4 and α- and β-defensins and regulated complement activation through mannose-binding lectin 2. The expression of the receptor that regulates the secretion of IgA into the intestinal lumen, the polymeric immunoglobulin receptor, was also dependent on IL-17RA signaling. Interestingly, the transcriptome data showed for the first time the involvement of the circadian clock in the host response following Giardia infection.
Miyauchi, Eiji; O'Callaghan, John; Buttó, Ludovica F; Hurley, Gráinne; Melgar, Silvia; Tanabe, Soichi; Shanahan, Fergus; Nally, Kenneth; O'Toole, Paul W
2012-11-01
Enhanced barrier function is one mechanism whereby commensals and probiotic bacteria limit translocation of foreign antigens or pathogens in the gut. However, barrier protection is not exhibited by all probiotic or commensals and the strain-specific molecules involved remain to be clarified. We evaluated the effects of 33 individual Lactobacillus salivarius strains on the hydrogen peroxide (H(2)O(2))-induced barrier impairment in human epithelial Caco-2 cells. These strains showed markedly different effects on H(2)O(2)-induced reduction in transepithelial resistance (TER). The effective strains such as UCC118 and CCUG38008 attenuated H(2)O(2)-induced disassembly and relocalization of tight junction proteins, but the ineffective strain AH43324 did not. Strains UCC118 and CCUG38008 induced phosphorylation of extracellular signal-regulated kinase (ERK) in Caco-2 cells, and the ERK inhibitor U0126 attenuated the barrier-protecting effect of these strains. In contrast, the AH43324 strain induced phosphorylation of Akt and p38, which was associated with an absence of a protective effect. Global transcriptome analysis of UCC118 and AH43324 revealed that some genes in a bacteriocin gene cluster were upregulated in AH43324 under TER assay conditions. A bacteriocin-negative UCC118 mutant displayed significantly greater suppressive effect on H(2)O(2)-induced reduction in TER compared with wild-type UCC118. The wild-type strain augmented H(2)O(2)-induced phosphorylation of Akt and p38, whereas a bacteriocin-negative UCC118 mutant did not. These observations indicate that L. salivarius strains are widely divergent in their capacity for barrier protection, and this is underpinned by differences in the activation of intracellular signaling pathways. Furthermore, bacteriocin production appears to have an attenuating influence on lactobacillus-mediated barrier protection.
Park, Bom; Hwang, Eunson; Seo, Seul A; Cho, Jin-Gyeong; Yang, Jung-Eun; Yi, Tae-Hoo
2018-01-01
UV irradiation triggers the overproduction of matrix metalloproteinases and collagen degradation, which in turn causes increased pigmentation, dryness, and deep wrinkling of the skin. These chronic symptoms are collectively referred to as photoaging. Eucalyptus globulus is an evergreen tree that is widely used in cosmetics because of its antimicrobial activity. In this study, we investigated the protective effect of 50% ethanol extracts of Eucalyptus globulus on UV-induced photoaging in vitro and in vivo. Normal human dermal fibroblasts were treated with Eucalyptus globulus at concentrations ranging from 1 to 100 μg/mL after UVB or non-UVB irradiation. We found that Eucalyptus globulus suppressed the expression of MMPs and IL-6, but increased the expression of TGF-β1 and procollagen type 1. In addition, Eucalyptus globulus inhibited activation of the AP-1 transcription factor, an inducer of MMPs. Eucalyptus globulus was also found to regulate TGF-β/Smad signaling by reversing the activity of negative Smad regulators. Lastly, in vivo studies showed that topical application of Eucalyptus globulus on UVB-irradiated hairless mice reduced wrinkle formation and dryness by down-regulating MMP-1 and up-regulating expression of elastin, TGF-β1, and procollagen type 1. Taken together, these data suggest that Eucalyptus globulus may be a useful agent in cosmetic products. Copyright © 2017 Elsevier Inc. All rights reserved.
40 CFR 62.5375 - Identification of plan-negative declaration.
Code of Federal Regulations, 2010 CFR
2010-07-01
...—negative declaration. The State Department of Environmental Quality Engineering submitted on July 31, 1979... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of plan-negative declaration. 62.5375 Section 62.5375 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...
40 CFR 57.816 - Effect of negative recommendation.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Effect of negative recommendation. 57.816 Section 57.816 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Reduction Technology § 57.816 Effect of negative recommendation. No waiver of the interim requirement for...
Mindfulness facets and problematic Internet use: A six-month longitudinal study.
Calvete, Esther; Gámez-Guadix, Manuel; Cortazar, Nerea
2017-09-01
The aim of this study was to study the cross-sectional and longitudinal associations between mindfulness facets and problematic Internet use in adolescents. The sample consisted of 609 adolescents (313 girls, 296 boys; Mean age=14.21years, SD=1.71; age range 11-18). Participants completed a measure of five facets of mindfulness (describing, observing, acting with awareness, non-judging and non-reacting) at the beginning of the year, and measures of several components of problematic Internet use (preference for online social interactions, the use of the Internet to regulate mood, deficient self-regulation and negative outcomes) at beginning of the year and six months later. Findings indicated that non-judging is the only dimension of mindfulness that predicts a decrease in preference for online social interactions over face-to-face relationships. Moreover, non-judging indirectly predicted reductions in the rest of the problematic Internet use components. The observing and acting with awareness dimensions of mindfulness directly predicted less deficient self-regulation of Internet use and indirectly predicted less negative outcomes through their impact on deficient self-regulation. Thus, these dimensions seem to act when the maladaptive use of the Internet is consolidated. These findings suggest that interventions should include approaches to develop those mindfulness facets that protect against the development of problematic Internet use. Copyright © 2017 Elsevier Ltd. All rights reserved.
Ismail, Ku Syahidah Ku; Sakamoto, Takatoshi; Hatanaka, Haruyo; Hasunuma, Tomohisa; Kondo, Akihiko
2013-01-10
Production of ethanol from xylose at high temperature would be an economical approach since it reduces risk of contamination and allows both the saccharification and fermentation steps in SSF to be running at elevated temperature. Eight recombinant xylose-utilizing Saccharomyces cerevisiae strains developed from industrial strains were constructed and subjected to high-temperature fermentation at 38 °C. The best performing strain was sun049T, which produced up to 15.2 g/L ethanol (63% of the theoretical production), followed by sun048T and sun588T, both with 14.1 g/L ethanol produced. Via transcriptomic analysis, expression profiling of the top three best ethanol producing strains compared to a negative control strain, sun473T, led to the discovery of genes in common that were regulated in the same direction. Identification of the 20 most highly up-regulated and the 20 most highly down-regulated genes indicated that the cells regulate their central metabolism and maintain the integrity of the cell walls in response to high temperature. We also speculate that cross-protection in the cells occurs, allowing them to maintain ethanol production at higher concentration under heat stress than the negative controls. This report provides further transcriptomics information in the interest of producing a robust microorganism for high-temperature ethanol production utilizing xylose. Copyright © 2012 Elsevier B.V. All rights reserved.
Intestinal alkaline phosphatase regulates protective surface microclimate pH in rat duodenum.
Mizumori, Misa; Ham, Maggie; Guth, Paul H; Engel, Eli; Kaunitz, Jonathan D; Akiba, Yasutada
2009-07-15
Regulation of localized extracellular pH (pH(o)) maintains normal organ function. An alkaline microclimate overlying the duodenal enterocyte brush border protects the mucosa from luminal acid. We hypothesized that intestinal alkaline phosphatase (IAP) regulates pH(o) due to pH-sensitive ATP hydrolysis as part of an ecto-purinergic pH regulatory system, comprised of cell-surface P2Y receptors and ATP-stimulated duodenal bicarbonate secretion (DBS). To test this hypothesis, we measured DBS in a perfused rat duodenal loop, examining the effect of the competitive alkaline phosphatase inhibitor glycerol phosphate (GP), the ecto-nucleoside triphosphate diphosphohydrolase inhibitor ARL67156, and exogenous nucleotides or P2 receptor agonists on DBS. Furthermore, we measured perfusate ATP concentration with a luciferin-luciferase bioassay. IAP inhibition increased DBS and luminal ATP output. Increased luminal ATP output was partially CFTR dependent, but was not due to cellular injury. Immunofluorescence localized the P2Y(1) receptor to the brush border membrane of duodenal villi. The P2Y(1) agonist 2-methylthio-ADP increased DBS, whereas the P2Y(1) antagonist MRS2179 reduced ATP- or GP-induced DBS. Acid perfusion augmented DBS and ATP release, further enhanced by the IAP inhibitor l-cysteine, and reduced by the exogenous ATPase apyrase. Furthermore, MRS2179 or the highly selective P2Y(1) antagonist MRS2500 co-perfused with acid induced epithelial injury, suggesting that IAP/ATP/P2Y signalling protects the mucosa from acid injury. Increased DBS augments IAP activity presumably by raising pH(o), increasing the rate of ATP degradation, decreasing ATP-mediated DBS, forming a negative feedback loop. The duodenal epithelial brush border IAP-P2Y-HCO(3-) surface microclimate pH regulatory system effectively protects the mucosa from acid injury.
Jiang, Ding-Sheng; Liu, Yu; Zhou, Heng; Zhang, Yan; Zhang, Xiao-Dong; Zhang, Xiao-Fei; Chen, Ke; Gao, Lu; Peng, Juan; Gong, Hui; Chen, Yingjie; Yang, Qinglin; Liu, Peter P.; Fan, Guo-Chang; Zou, Yunzeng; Li, Hongliang
2017-01-01
Cardiac hypertrophy is a complex pathological process that involves multiple factors including inflammation and apoptosis. Interferon regulatory factor 7 (IRF7) is a multifunctional regulator that participates in immune regulation, cell differentiation, apoptosis, and oncogenesis. However, the role of IRF7 in cardiac hypertrophy remains unclear. We performed aortic banding in cardiac-specific IRF7 transgenic mice, IRF7 knockout mice, and the wild-type littermates of these mice. Our results demonstrated that IRF7 was downregulated in aortic banding–induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 48 hours. Accordingly, heart-specific overexpression of IRF7 significantly attenuated pressure overload–induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of IRF7 led to opposite effects. Moreover, IRF7 protected against angiotensin II–induced cardiomyocyte hypertrophy in vitro. Mechanistically, we identified that IRF7-dependent cardioprotection was mediated through IRF7 binding to inhibitor of κB kinase-β, and subsequent nuclear factor-κB inactivation. In fact, blocking nuclear factor-κB signaling with cardiac-specific inhibitors of κBαS32A/S36A super-repressor transgene counteracted the adverse effect of IRF7 deficiency. Conversely, activation of nuclear factor-κB signaling via a cardiac-specific conditional inhibitor of κB kinase-βS177E/S181E (constitutively active) transgene negated the antihypertrophic effect of IRF7 overexpression. Our data demonstrate that IRF7 acts as a novel negative regulator of pathological cardiac hypertrophy by inhibiting nuclear factor-κB signaling and may constitute a potential therapeutic target for pathological cardiac hypertrophy. PMID:24396025
Zhang, Hui; Wang, Zhenhong; You, Xuqun; Lü, Wei; Luo, Yun
2015-09-01
The aim of the current study was to examine the direct and interactive effects of two types of narcissism (overt and covert) and respiratory sinus arrhythmia (RSA) reactivity on emotion regulation difficulties in 227 undergraduate students. Overt and covert narcissism and emotion regulation difficulties were assessed with self-report measures (narcissistic personality inventory (NPI)-16, hypersensitive narcissism scale (HSNS), and difficulties in emotion regulation scale (DERS)), and physiological data were measured during the baseline, stress (a public-speaking task), and recovery periods in the laboratory. Results indicated that overt narcissism was negatively related to a lack of emotional awareness and emotional clarity, whereas covert narcissism was positively related to overall emotion regulation difficulties, nonacceptance of emotional responses, impulse control difficulties, limited access to emotion regulation strategies, and a lack of emotional clarity. RSA reactivity in response to a mock job interview moderated the associations between covert narcissism (as a predictor) and overall emotion regulation difficulties and impulse control difficulties (as outcomes). This finding showed that a greater stress-induced RSA decrease may serve as a protective factor and ameliorate the effect of covert narcissism on individuals' emotion regulation difficulties. Copyright © 2015 Elsevier B.V. All rights reserved.
Williamson, Tracy P; Johnson, Delinda A; Johnson, Jeffrey A
2012-06-01
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that binds to the antioxidant response element, a cis-acting regulatory element that increases expression of detoxifying enzymes and antioxidant proteins. Kelch-like ECH associating protein 1 (Keap1) protein is a negative regulator of Nrf2. Previous work has shown that genetic overexpression of Nrf2 is protective in vitro and in vivo. To modulate the Nrf2-ARE system without overexpressing Nrf2, we used short interfering RNA (siRNA) directed against Keap1. Keap1 siRNA administration in primary astrocytes increased the levels of Nrf2-ARE driven genes and protected against oxidative stress. Moreover, Keap1 siRNA resulted in a persistent upregulation of the Nrf2-ARE pathway and protection against oxidative stress in primary astrocytes. Keap1 siRNA injected into the striatum was also modestly protective against MPTP-induced dopaminergic terminal damage. These data indicate that activation of endogenous intracellular levels of Nrf2 is sufficient to protect in models of oxidative stress and Parkinson's disease. Copyright © 2012 Elsevier Inc. All rights reserved.
Lei, Chao; Wang, Jingzhi; Liu, Yuanyuan; Liu, Xinqiang; Zhao, Guoping; Wang, Jin
2018-01-29
Due to the important role of rifamycin in curing tuberculosis infection, the study on rifamycin has never been stopped. Although RifZ, which locates within the rifamycin biosynthetic cluster, has recently been characterized as a pathway-specific regulator for rifamycin biosynthesis, little is known about the regulation of rifamycin export. In this work, we proved that the expression of the rifamycin efflux pump (RifP) was regulated by RifQ, a TetR-family transcriptional regulator. Deletion of rifQ had little impact on bacterial growth, but resulted in improved rifamycin production, which was consistent with the reverse transcription PCR results that RifQ negatively regulated rifP's transcription. With electrophoretic mobility shift assay and DNase I Footprinting assay, RifQ was found to directly bind to the promoter region of rifP, and a typical inverted repeat was identified within the RifQ-protected sequences. The transcription initiation site of rifP was further characterized and found to be upstream of the RifQ binding sites, well explaining the RifQ-mediated repression of rifP's transcription in vivo. Moreover, rifamycin B (the end product of rifamycin biosynthesis) remarkably decreased the DNA binding affinity of RifQ, which led to derepression of rifamycin export, reducing the intracellular concentration of rifamycin B as well as its toxicity against the host. Here, we proved that the export of rifamycin B was repressed by RifQ in Amycolatopsis mediterranei, and the RifQ-mediated repression could be specifically relieved by rifamycin B, the end product of rifamycin biosynthesis, based on which a feedback model was proposed for regulation of rifamycin export. With the findings here, one could improve the antibiotic yield by simply inactivating the negative regulator of the antibiotic transporter.
[Information hygiene and regulation of information for vulnerable groups of the population].
Denisov, E I; Eremin, A L; Sivochalova, O V; Kurerov, N N
2014-01-01
Development of information society engenders the problem of hygienic regulation of information load for the population, first of all for vulnerable groups. There are presented international and Russian normative legal documents and experience in this area, there are described the negative effects of information (such as stress, depression, suicidal ideations). There are considered social-psychological characteristics of vulnerable groups that requires their best protection from loads of information, doing harm, particularly in terms of reproductive health, family relationships, children, etc. There was noted the desirability of improvement of sanitary, legislation on the regulation of the information load on the population, especially in vulnerable groups, in terms of optimization of parameters of the signal-carriers on volume, brightness and the adequacy of the volume and content of information in radio and television broadcasting, in an urban environment and at the plant to preserve the health and well-being of the population.
Legarda, Diana; Justus, Scott J; Ang, Rosalind L; Rikhi, Nimisha; Li, Wenjing; Moran, Thomas M; Zhang, Jianke; Mizoguchi, Emiko; Zelic, Matija; Kelliher, Michelle A; Blander, J Magarian; Ting, Adrian T
2016-06-14
Tumor necrosis factor (TNF) induces necroptosis, a RIPK3/MLKL-dependent form of inflammatory cell death. In response to infection by Gram-negative bacteria, multiple receptors on macrophages, including TLR4, TNF, and type I IFN receptors, are concurrently activated, but it is unclear how they crosstalk to regulate necroptosis. We report that TLR4 activates CASPASE-8 to cleave and remove the deubiquitinase cylindromatosis (CYLD) in a TRIF- and RIPK1-dependent manner to disable necroptosis in macrophages. Inhibiting CASPASE-8 leads to CYLD-dependent necroptosis caused by the TNF produced in response to TLR4 ligation. While lipopolysaccharides (LPS)-induced necroptosis was abrogated in Tnf(-/-) macrophages, a soluble TNF antagonist was not able to do so in Tnf(+/+) macrophages, indicating that necroptosis occurs in a cell-autonomous manner. Surprisingly, TNF-mediated auto-necroptosis of macrophages requires type I IFN, which primes the expression of key necroptosis-signaling molecules, including TNFR2 and MLKL. Thus, the TNF necroptosis pathway is regulated by both negative and positive crosstalk. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
Benefits of emotional integration and costs of emotional distancing.
Roth, Guy; Shahar, Bat-Hen; Zohar-Shefer, Yael; Benita, Moti; Moed, Anat; Bibi, Uri; Kanat-Maymon, Yaniv; Ryan, Richard M
2017-12-09
Three studies explored the consequences of the self-determination theory conception of integrative emotion regulation (IER; Ryan & Deci, 2017), which involves an interested stance toward emotions. Emotional, physiological, and cognitive consequences of IER were compared to the consequences of emotional distancing (ED), in relation to a fear-eliciting film. In Study 1, we manipulated emotion regulation by prompting students' (N = 90) IER and ED and also included a control group. Then we tested groups' defensive versus nondefensive emotional processing, coded from post-film written texts. Study 2 (N = 90) and Study 3 (N = 135) used the same emotion regulation manipulations but exposed participants to the fear-eliciting film twice, 72 hr apart, to examine each style's protection from adverse emotional, physiological, and cognitive costs at second exposure. Participants who had been prompted to practice IER were expected to benefit more than participants in the ED and control groups at second exposure, as manifested in lower arousal and better cognitive capacity. Overall, results supported our hypotheses. The current studies provide some support for the assumption that in comparison to ED, taking interest in and accepting one's negative emotions are linked with less defensive processing of negative experiences and with better functioning. © 2017 Wiley Periodicals, Inc.
Raccanello, Daniela; Burro, Roberto; Brondino, Margherita; Pasini, Margherita
2018-04-01
Notwithstanding the dramatically increasing frequency of acts of terrorism in Europe and the extent of their media coverage, there is lack of knowledge on people's affective reactions and associated emotion regulation strategies. We explored the affective impact on two cohorts of Italian students (n = 193) possibly exposed vicariously through the mass media to the 2015 Paris or the 2016 Brussels terrorist attacks, respectively. We accessed data from three online questionnaires: one on emotion regulation administered before each attack; one on daily affect administered just before and after each attack; and one on causes of weekly affect and life satisfaction administered at the end of the week in which each attack occurred. The attacks were perceived as relevant for influencing negative affect for 22% of the students. For them, suppression-less frequently used than reappraisal-was associated with an improvement of affect after each attack but negatively related to life satisfaction concerning the week in which the attacks occurred. Our data showed that the recent terrorist attacks occurring in Europe had an affective impact on people at some distance who were vicariously exposed and point to the protective role of emotion regulation as a key resource for individuals' well-being. Copyright © 2017 John Wiley & Sons, Ltd.
Gukovskaya, Anna S; Gukovsky, Ilya; Jung, Yoon; Mouria, Michelle; Pandol, Stephen J
2002-06-21
Apoptosis and necrosis are critical parameters of pancreatitis, the mechanisms of which remain unknown. Many characteristics of pancreatitis can be studied in vitro in pancreatic acini treated with high doses of cholecystokinin (CCK). We show here that CCK stimulates apoptosis and death signaling pathways in rat pancreatic acinar cells, including caspase activation, cytochrome c release, and mitochondrial depolarization. The mitochondrial dysfunction is mediated by upstream caspases (possibly caspase-8) and, in turn, leads to activation of caspase-3. CCK causes mitochondrial alterations through both permeability transition pore-dependent (cytochrome c release) and permeability transition pore-independent (mitochondrial depolarization) mechanisms. Caspase activation and mitochondrial alterations also occur in untreated pancreatic acinar cells; however, the underlying mechanisms are different. In particular, caspases protect untreated acinar cells from mitochondrial damage. We found that caspases not only mediate apoptosis but also regulate other parameters of CCK-induced acinar cell injury that are characteristic of pancreatitis; in particular, caspases negatively regulate necrosis and trypsin activation in acinar cells. The results suggest that the observed signaling pathways regulate parenchymal cell injury and death in CCK-induced pancreatitis. Protection against necrosis and trypsin activation by caspases can explain why the severity of pancreatitis in experimental models correlates inversely with the extent of apoptosis.
Completing the Circle: A Model for Effective Community Review of Environmental Health Research
Shepard, Peggy Morrow; Corbin-Mark, Cecil D.
2009-01-01
While it is well understood that multiple and cumulative environmental stressors negatively impact health at the community level, existing ethical research review procedures are designed to protect individual research participants but not communities. Increasing concerns regarding the ethical conduct of research in general and environmental and genetic research in particular underscore the need to expand the scope of current human participant research regulations and ethical guidelines to include protections for communities. In an effort to address this issue, West Harlem Environmental Action (WE ACT), a nonprofit, community-based environmental justice organization in New York City that has been involved in community–academic partnerships for the past decade, used qualitative interview data to develop a pilot model for community review of environmental health science research. PMID:19890159
Public protection - reliable allergen risk management
NASA Astrophysics Data System (ADS)
Janković, V.; Popov Raljić, J.; Đorđević, V.
2017-09-01
Consumers with potentially fatal food allergies are dependent on correct product labelling to protect their health. The food industry is responsible for providing every detail consumers need to make informed decisions. Considering public health, food suppliers have to monitor the presence of allergens, prevent cross-contamination and label products accurately. Allergen labelling of food products, drinks and non pre-packed food and drink products is clearly defined with legal regulations. To achieve this, a complete understanding of each product’s allergenic ingredients is needed and cross-contamination of food with allergens must be avoided. Raw materials need to be checked, every ingredient must be verified and every single allergen has to be stipulated. A mislabeled product could be recalled at potential cost, financially damaging business and at the same time, negatively impacting brand and reputation.
Ben-Nathan, D; Padgett, D A; Loria, R M
1999-05-01
The protective effects of the hormones androstenediol (androstene-3beta, 17beta,-diol; AED) and dehydroepiandrosterone (5-androsten-3beta-ol-17-one; DHEA) on the pathophysiology of two lethal bacterial infections and endotoxin shock were examined. The infections included a gram-positive organism (Enterococcus faecalis) and a gram-negative organism (Pseudomonas aeruginosa). Both hormones protected mice from the lethal bacterial infections and from lipopolysaccharide (LPS) challenge. Treatment of animals lethally infected with P. aeruginosa with DHEA resulted in a 43% protection whereas treatment with AED gave a 67% protection. Both hormones also protected completely animals infected with an LD50 dose of E. faecalis. Similarly, the 88% mortality rate seen in LPS challenge was reduced to 17% and 8.5%, by treatment with DHEA and AED, respectively. The protective influences of both steroids were shown not to be directly antibacterial, but primarily an indirect antitoxin reaction. DHEA appears to mediate its protective effect by a mechanism that blocks the toxin-induced production of pathophysiological levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1. AED usually had greater protective effects than DHEA; however, the AED effect was independent of TNF-alpha suppression, both in vivo and in vitro. The data suggest that both DHEA and AED may have a role in the neuro-endocrine regulation of antibacterial immune resistance.
The perils of protection: vulnerability and women in clinical research.
Schonfeld, Toby
2013-06-01
Subpart B of 45 Code of Federal Regulations Part 46 (CFR) identifies the criteria according to which research involving pregnant women, human fetuses, and neonates can be conducted ethically in the United States. As such, pregnant women and fetuses fall into a category requiring "additional protections," often referred to as "vulnerable populations." The CFR does not define vulnerability, but merely gives examples of vulnerable groups by pointing to different categories of potential research subjects needing additional protections. In this paper, I assess critically the role of this categorization of pregnant women involved in research as "vulnerable," both as separate entities and in combination with the fetuses they carry. In particular, I do three things: (1) demonstrate that pregnant women qua pregnancy are either not "vulnerable" according to any meaningful definition of that term or that such vulnerability is irrelevant to her status as a research participant; (2) argue that while a fetus may be vulnerable in terms of dependency, this categorization does not equate to the vulnerability of the pregnant woman; and (3) suggest that any vulnerability that appends to women is precisely the result of federal regulations and dubious public perceptions about pregnant women. I conclude by demonstrating how this erroneous characterization of pregnant women as "vulnerable" and its associated protections have not only impeded vital research for pregnant women and their fetuses, but have also negatively affected the inclusion of all women in clinical research.
Feng, Xing; Li, Jing; Liu, Jinyu; Jin, Minghua; Liu, Xiaomei; Du, Haiying; Zhang, Long; Sun, Zhiwei; Li, Xiaoguang
2011-03-01
We investigated protective effect of FK506 on rat hearts subjected to ischemia/reperfusion (I/R) injury by regulating CaN and ASK1. Wistar rats were divided into four groups: Ischemia/reperfusion group (I/R), FK506 + Ischemia/reperfusion group (FK506-I/R), sham group, and FK506 + sham group (FK506-sham). Ischemia/reperfusion was achieved by occluding left coronary artery for 30 min and subsequently reperfusing for 120 min. FK506 was administered 15 min before ischemia. Rats in sham group and FK506-sham group were operated only by placing a ligature around the coronary artery, and the blood supply was not blocked. I/R group showed a rapid increase in TUNEL-positive cells and high risks of histopathological changes in damaged cardiac tissues. FK506 reduced the infarct size and inhibited the activation of CaN enzyme in FK506-I/R group. Increase in Bcl-2/Bax ratio in FK506-IR group indicated that FK506 protected myocardium from apoptosis induced by IR. The activity of CaN and ASK1 protein level decreased significantly after I/R injury in FK506-treated I/R heart. FK506 suppresses the activation of CaN and ASK1 through CaN-mediated apoptosis pathway, and ASK1 negatively regulates CaN activity. Suppression of CaN and ASK1 signaling circuitry are involved in protective effect of FK506 on rat myocardium I/R injury.
76 FR 75825 - Streamlining Inherited Regulations
Federal Register 2010, 2011, 2012, 2013, 2014
2011-12-05
... submitting comments. Mail: Research, Markets & Regulations Division, Bureau of Consumer Financial Protection... Lieu of Mail: Research, Markets & Regulations Division, Bureau of Consumer Financial Protection, 1700 G..., Counsel, Research, Markets & Regulations Division, Bureau of Consumer Financial Protection, (202) 453-7700...
Guadalupe-Grau, Amelia; Ara, Ignacio; Dorado, Cecilia; Vicente-Rodríguez, German; Perez-Gomez, Jorge; Cabrero, Javier Chavarren; Serrano-Sanchez, José A; Santana, Alfredo; Calbet, Jose A L
2010-10-01
Osteocalcin is a hormone produced by osteoblasts which acts as a negative regulator of fat mass, protecting against diet induced obesity and insulin resistance in rodents. To determine if an acute increase in osteocalcin concentration is associated with opposed changes in circulating leptin levels and insulin resistance we studied 15 middle and long distance male triathletes, (age 32.1 ± 6.9 years), before and 48 h after an Olympic (OT) or an Ironman (IT) triathlon competition. Muscle power, anaerobic capacity, body composition (dual-energy X-ray absorptiometry), and serum concentrations of testosterone, dihydrotestosterone, osteocalcin, leptin, glucose, insulin and insulin resistance (HOMA) were determined pre- and post-race. Pre- and 48 h post-race total and regional lean body mass was not altered, but fat mass was similarly increased (~250 g) 48 h after the competitions. This elicited an increase in plasma leptin of 33% after the IT while it remained unchanged after the OT, likely due to a 25% increase in plasma osteocalcin which occurred only after the OT (all p < 0.05). Post-race HOMA remained unchanged in OT and IT. Performance was normalized 48 h after the competitions, with the exception of a slightly lower jumping capacity after the IT. Serum testosterone concentration tended to decrease by 10% after the IT whilst dihydrotestosterone was reduced by 24% after the IT. In conclusion, an acute increase in serum osteocalcin concentration blunts the expected increase of serum leptin concentration that should occur with fat mass gain. This study provides evidence for osteocalcin as a negative regulator of serum leptin in humans.
Kim, Sanghag; Kochanska, Grazyna
2012-01-01
This study examined infants’ negative emotionality as moderating the effect of parent-child Mutually Responsive Orientation (MRO) on children’s self-regulation (N=102). Negative emotionality was observed in anger-eliciting episodes and in interactions with parents at 7 months. MRO was coded in naturalistic interactions at 15 months. Self-regulation was measured at 25 months in effortful control battery and as self-regulated compliance to parental requests and prohibitions. Negative emotionality moderated the effects of mother-child MRO. Highly negative infants were less self-regulated when they were in unresponsive relationships (low MRO), but more self-regulated when in responsive relationships (high MRO). For infants not prone to negative emotionality, there was no link between MRO and self-regulation. The “regions-of-significance” analysis supported the differential susceptibility model not the diathesis-stress model. PMID:22670684
Lin, Sue-Jane; Chang, Chungming; Ng, Ah-Kau; Wang, Shu-Han; Li, Jia-Je; Hu, Cheng-po
2007-09-01
In this study, we demonstrate that interleukin-4 (IL-4) protects human hepatocellular carcinoma (HCC) cell line Hep3B from apoptosis induced by transforming growth factor-beta (TGF-beta). Further investigation of IL-4-transduced signaling pathways revealed that both insulin response substrate 1 and 2 (IRS-1/-2) and extracellular signal-regulated kinase (ERK) pathways were activated after IL-4 stimulation. The IRS-1/-2 activation was accompanied by the activation of phosphotidylinositol-3-kinase (PI3K), leading to Akt and p70 ribosomal protein S6 kinase (p70S6K). Interestingly, a protein kinase C (PKC) inhibitor, Gö6976, inhibited the phosphorylation of Akt, suggesting that the Akt activation was PKC-dependent. Using specific inhibitors for PI3K or ERK, we demonstrated that the PI3K pathway, but not the ERK pathway, was required for protection. The constitutively active form of PI3K almost completely rescued TGF-beta-induced apoptosis, further supporting the importance of the PI3K pathway in the protective effect of IL-4. Furthermore, a dominant negative Akt and/or Gö6976 only partially blocked the anti-apoptotic effect of IL-4. Similarly, rapamycin, which interrupted the activation of p70S6K, also only partially blocked the protective effect of IL-4. However, in the presence of both rapamycin and dominant negative Akt with or without Gö6976, IL-4 almost completely lost the anti-apoptotic effect, suggesting that both Akt and p70S6K pathways were required for the protective effect of IL-4 against TGF-beta-induced apoptosis.
Identification of Genes that Maintain Behavioral and Structural Plasticity during Sleep Loss
Seugnet, Laurent; Dissel, Stephane; Thimgan, Matthew; Cao, Lijuan; Shaw, Paul J.
2017-01-01
Although patients with primary insomnia experience sleep disruption, they are able to maintain normal performance on a variety of cognitive tasks. This observation suggests that insomnia may be a condition where predisposing factors simultaneously increase the risk for insomnia and also mitigate against the deleterious consequences of waking. To gain insight into processes that might regulate sleep and buffer neuronal circuits during sleep loss, we manipulated three genes, fat facet (faf), highwire (hiw) and the GABA receptor Resistance to dieldrin (Rdl), that were differentially modulated in a Drosophila model of insomnia. Our results indicate that increasing faf and decreasing hiw or Rdl within wake-promoting large ventral lateral clock neurons (lLNvs) induces sleep loss. As expected, sleep loss induced by decreasing hiw in the lLNvs results in deficits in short-term memory and increases of synaptic growth. However, sleep loss induced by knocking down Rdl in the lLNvs protects flies from sleep-loss induced deficits in short-term memory and increases in synaptic markers. Surprisingly, decreasing hiw and Rdl within the Mushroom Bodies (MBs) protects against the negative effects of sleep deprivation (SD) as indicated by the absence of a subsequent homeostatic response, or deficits in short-term memory. Together these results indicate that specific genes are able to disrupt sleep and protect against the negative consequences of waking in a circuit dependent manner. PMID:29109678
Measuring Generalized Expectancies for Negative Mood Regulation.
ERIC Educational Resources Information Center
Catanzaro, Salvatore J.; Mearns, Jack
Research has suggested the utility of studying individual differences in the regulation of negative mood states. Generalized response expectancies for negative mood regulation were defined as expectancies that some overt behavior or cognition would alleviate negative mood states as they occur across situations. The Generalized Expectancy for…
40 CFR 52.1483 - Malfunction regulations.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Malfunction regulations. 52.1483 Section 52.1483 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... regulations. (a) The following regulations are disapproved because they would permit the exemption of sources...
40 CFR 52.1483 - Malfunction regulations.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Malfunction regulations. 52.1483 Section 52.1483 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... regulations. (a) The following regulations are disapproved because they would permit the exemption of sources...
Mask, Lisa; Blanchard, Céline M
2011-09-01
The present study examines the protective role of an autonomous regulation of eating behaviors (AREB) on the relationship between trait body dissatisfaction and women's body image concerns and eating-related intentions in response to "thin ideal" media. Undergraduate women (n=138) were randomly assigned to view a "thin ideal" video or a neutral video. As hypothesized, trait body dissatisfaction predicted more negative affect and size dissatisfaction following exposure to the "thin ideal" video among women who displayed less AREB. Conversely, trait body dissatisfaction predicted greater intentions to monitor food intake and limit unhealthy foods following exposure to the "thin ideal" video among women who displayed more AREB. Copyright © 2011 Elsevier Ltd. All rights reserved.
TPP1 is a homologue of ciliate TEBP-β and interacts with POT1 to recruit telomerase
NASA Astrophysics Data System (ADS)
Xin, Huawei; Liu, Dan; Wan, Ma; Safari, Amin; Kim, Hyeung; Sun, Wen; O'Connor, Matthew S.; Songyang, Zhou
2007-02-01
Telomere dysfunction may result in chromosomal abnormalities, DNA damage responses, and even cancer. Early studies in lower organisms have helped to establish the crucial role of telomerase and telomeric proteins in maintaining telomere length and protecting telomere ends. In Oxytricha nova, telomere G-overhangs are protected by the TEBP-α/β heterodimer. Human telomeres contain duplex telomeric repeats with 3' single-stranded G-overhangs, and may fold into a t-loop structure that helps to shield them from being recognized as DNA breaks. Additionally, the TEBP-α homologue, POT1, which binds telomeric single-stranded DNA (ssDNA), associates with multiple telomeric proteins (for example, TPP1, TIN2, TRF1, TRF2 and RAP1) to form the six-protein telosome/shelterin and other subcomplexes. These telomeric protein complexes in turn interact with diverse pathways to form the telomere interactome for telomere maintenance. However, the mechanisms by which the POT1-containing telosome communicates with telomerase to regulate telomeres remain to be elucidated. Here we demonstrate that TPP1 is a putative mammalian homologue of TEBP-β and contains a predicted amino-terminal oligonucleotide/oligosaccharide binding (OB) fold. TPP1-POT1 association enhanced POT1 affinity for telomeric ssDNA. In addition, the TPP1 OB fold, as well as POT1-TPP1 binding, seemed critical for POT1-mediated telomere-length control and telomere-end protection in human cells. Disruption of POT1-TPP1 interaction by dominant negative TPP1 expression or RNA interference (RNAi) resulted in telomere-length alteration and DNA damage responses. Furthermore, we offer evidence that TPP1 associates with the telomerase in a TPP1-OB-fold-dependent manner, providing a physical link between telomerase and the telosome/shelterin complex. Our findings highlight the critical role of TPP1 in telomere maintenance, and support a yin-yang model in which TPP1 and POT1 function as a unit to protect human telomeres, by both positively and negatively regulating telomerase access to telomere DNA.
Nakatsu, Yusuke; Iwashita, Misaki; Sakoda, Hideyuki; Ono, Hiraku; Nagata, Kengo; Matsunaga, Yasuka; Fukushima, Toshiaki; Fujishiro, Midori; Kushiyama, Akifumi; Kamata, Hideaki; Takahashi, Shin-Ichiro; Katagiri, Hideki; Honda, Hiroaki; Kiyonari, Hiroshi; Uchida, Takafumi; Asano, Tomoichiro
2015-01-01
AMP-activated protein kinase (AMPK) plays a critical role in metabolic regulation. In this study, first, it was revealed that Pin1 associates with any isoform of γ, but not with either the α or the β subunit, of AMPK. The association between Pin1 and the AMPK γ1 subunit is mediated by the WW domain of Pin1 and the Thr211-Pro-containing motif located in the CBS domain of the γ1 subunit. Importantly, overexpression of Pin1 suppressed AMPK phosphorylation in response to either 2-deoxyglucose or biguanide stimulation, whereas Pin1 knockdown by siRNAs or treatment with Pin1 inhibitors enhanced it. The experiments using recombinant Pin1, AMPK, LKB1, and PP2C proteins revealed that the protective effect of AMP against PP2C-induced AMPKα subunit dephosphorylation was markedly suppressed by the addition of Pin1. In good agreement with the in vitro data, the level of AMPK phosphorylation as well as the expressions of mitochondria-related genes, such as PGC-1α, which are known to be positively regulated by AMPK, were markedly higher with reduced triglyceride accumulation in the muscles of Pin1 KO mice as compared with controls. These findings suggest that Pin1 plays an important role in the pathogenic mechanisms underlying impaired glucose and lipid metabolism, functioning as a negative regulator of AMPK. PMID:26276391
Villarosa, Margo C; Moorer, Kayla D; Madson, Michael B; Zeigler-Hill, Virgil; Noble, Jeremy J
2014-09-01
The link between social anxiety and alcohol-related negative consequences among college students has been well documented. Protective behavioral strategies are cognitive-behavioral strategies that college students use in an effort to reduce harm while they are drinking. In the current study we examined the mediating role of the 2 categories of protective behavioral strategies (i.e., controlled consumption and serious harm reduction) in the relationship that social anxiety symptoms have with alcohol-related negative consequences. Participants were 572 undergraduates who completed measures of social anxiety, alcohol use, negative consequences of alcohol use, and protective behavioral strategy use. Only serious harm reduction strategies emerged as a mediator of the association that social anxiety symptoms had with alcohol-related negative consequences. Clinical and research implications are discussed.
Emotion dysregulation and negative affect: Laboratory and EMA investigations in smokers.
MacIntyre, Jessica M; Ruscio, Aimee C; Brede, Emily; Waters, Andrew J
2018-06-01
Difficulties in emotion regulation are associated with addictive behaviors, including smoking. Difficulties in emotion regulation may underlie large, rapid changes in negative affect that can increase likelihood of relapse. We investigated the association between emotion regulation ability and negative affect in smokers assessed both in the laboratory and in the field using Ecological Momentary Assessment. Adult community smokers ( N = 44) carried a personal digital assistant (PDA) for two weeks and were instructed to complete assessments of negative affect multiple times per day. Participants were instructed that they could smoke as much or as little as they liked. The Difficulties in Emotion Regulation Scale (DERS) and the Positive and Negative Affect Schedule (PANAS) were completed at three lab visits. Participants with higher average DERS scores reported greater negative affect at lab visits. When a participant reported a DERS score at a lab visit higher than their individual average, they also reported higher negative affect at that lab visit. Participants with higher baseline DERS scores reported more labile negative affect during EMA than those with lower baseline DERS scores, and they also reported a higher maximum level of negative affect during EMA. Overall, the findings suggest that changes in emotion regulation are associated with negative affect and that emotion regulation ability is related to both the intensity and lability of negative affect. A better understanding of momentary changes in emotion regulation and negative affect may lead to improved interventions for preventing substance use relapse.
Negative Regulation of Violacein Biosynthesis in Chromobacterium violaceum.
Devescovi, Giulia; Kojic, Milan; Covaceuszach, Sonia; Cámara, Miguel; Williams, Paul; Bertani, Iris; Subramoni, Sujatha; Venturi, Vittorio
2017-01-01
In Chromobacteium violaceum , the purple pigment violacein is under positive regulation by the N -acylhomoserine lactone CviI/R quorum sensing system and negative regulation by an uncharacterized putative repressor. In this study we report that the biosynthesis of violacein is negatively controlled by a novel repressor protein, VioS. The violacein operon is regulated negatively by VioS and positively by the CviI/R system in both C. violaceum and in a heterologous Escherichia coli genetic background. VioS does not regulate the CviI/R system and apart from violacein, VioS, and quorum sensing regulate other phenotypes antagonistically. Quorum sensing regulated phenotypes in C. violaceum are therefore further regulated providing an additional level of control.
Jiménez-Castro, Mónica B; Negrete-Sánchez, Elsa; Casillas-Ramírez, Araní; Gulfo, Jose; Álvarez-Mercado, Ana I; Cornide-Petronio, María Eugenia; Gracia-Sancho, Jordi; Rodés, Juan; Peralta, Carmen
2017-04-25
In the present study, we examined the effects of cortisol on steatotic and non-steatotic liver grafts from brain-dead donors and characterized the underlying mechanisms involved. Non-steatotic liver grafts showed reduced cortisol and increased cortisone levels in association with up-regulation of enzymes that inactivate cortisol. Conversely, steatotic liver grafts exhibited increased cortisol and reduced cortisone levels. The enzymes involved in cortisol generation were overexpressed, and those involved in cortisol inactivation or clearance were down-regulated in steatotic liver grafts. Exogenous administration of cortisol negatively affected hepatic damage and survival rate in non-steatotic liver transplantation (LT); however, cortisol treatment up-regulated the phosphoinositide 3-kinase (PI3K)-protein kinase C (PKC) pathway, resulting in protection against the deleterious effects of brain-dead donors on damage and inflammatory response in steatotic LT as well as in increased survival of recipients. The present study highlights the differences in the role of cortisol and hepatic mechanisms that regulate cortisol levels based on the type of liver. Our findings suggest that cortisol treatment is a feasible and highly protective strategy to reduce the adverse effects of brain-dead donor livers in order to ultimately improve liver graft quality in the presence of steatosis, whereas cortisol treatment would not be recommended for non-steatotic liver grafts. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.
Kim-Spoon, Jungmeen; Cicchetti, Dante; Rogosch, Fred A.
2013-01-01
The longitudinal contributions of emotion regulation and emotion lability/negativity to internalizing symptomatology were examined in a low-income sample (171 maltreated and 151 nonmaltreated children, from age 7 to 10 years). Latent difference score models indicated that, for both maltreated and nonmaltreated children, emotion regulation was a mediator between emotion lability/negativity and internalizing symptomatology, whereas emotion lability/negativity was not a mediator between emotion regulation and internalizing symptomatology. Early maltreatment was associated with high emotion lability/negativity (age 7) that contributed to poor emotion regulation (age 8), which in turn was predictive of increases in internalizing symptomatology (from age 8 to 9). The results imply important roles of emotion regulation in the development of internalizing symptomatology, especially for children with high emotion lability/negativity. PMID:23034132
Xie, Bin; Li, Dalin; London, Stephanie J.; Palmer, Paula H.; Johnshon, C. Anderson; Li, Yan; Shih, Jean; Bergen, Andrew W.; Nishita, Denise; Swan, Gary E.; Ahn, Rosa; Conti, David V.
2014-01-01
Summary Objectives Monoamine oxidase A (MAOA) modulates metabolism of serotonin and dopamine metabolism, neurotransmitters involved in regulation of appetite and food intake. The gene coding for MAOA contains a 30-bp tandem repeat (uVNTR) polymorphism in its promoter region that has been previously identified to be associated with obesity with mixed findings in the literature. Our goals were to replicate the population effects of this functional polymorphism on obesity risk, and to further explore gender differences and interaction effects with negative stressors. Methods Analyses were conducted with data on genotypes, measured weight and height, and self-reported behavioral characteristics among 1,101 Chinese adolescents 11-15 years old living in Wuhan, China. Results Girls with the high activity allele had significantly lower BMI (β=-0.25±0.98, p=0.011) compared to those with the low activity allele. Experience of negative familial stressors(e.g., death or illness of family members, hit or scolded by parents and increased quarreling with parents, parents argued frequently) significantly weakened this protective genetic effect on BMI (p for interaction=0.043). Stratified analyses showed a significant protective genetic effect on BMI only within the stratum of low stress level (β=-0.44±0.14, p=0.002). No similar effect was observed among boys. Conclusions Our findings confirm the genetic effects of MAOA uVNTR polymorphism on BMI in a Chinese adolescent population and suggest potential genetic interactions with negative familial stressors. PMID:23761378
Dvorak, Robert D.; Pearson, Matthew R.; Neighbors, Clayton; Martens, Matthew P.; Stevenson, Brittany L.; Kuvaas, Nicholas J.
2015-01-01
OBJECTIVE Drinking remains a problem across college campuses. Changing this behavior requires interventions that can be easily and widely dispersed. Several theories place intentions as a proximal predictor of behavior change. The current study examines the effects of a web-based Deviance Regulation Theory (DRT) intervention on (1) intentions to use alcohol protective behavior strategies (PBS) and (2) associations between these intentions and actual behavior. METHODS Participants (n = 76) completed a six-week, web-based, study examining drinking behaviors. Participants were randomly assigned to receive a positive frame about individuals who use PBS or a negative frame about individuals who do not. They also reported normative perceptions of PBS use among college students. They subsequently logged onto a secure server each week to report on alcohol involvement, use of three types of PBS (Manner of Drinking, Stopping/Limiting, and Serious Harm Reduction), and intentions to use these PBS the following week. RESULTS Consistent with DRT, negative frames resulted in higher PBS use intentions if individuals held high normative beliefs about PBS use. Positive frames resulted in higher Manner of Drinking PBS use intentions if individuals held low normative beliefs about PBS use, but only if individuals endorsed a high belief in the frame. In addition, there was a DRT consistent increase in intention-action associations, but only for Stopping/Limiting PBS. DISCUSSION A brief web-based DRT intervention was effective at increasing PBS intentions and increasing PBS intention-action associations. DRT may provide a mechanism to additively or synergistically improve other web-based interventions for college drinking. PMID:26914646
40 CFR 52.133 - Rules and regulations.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Rules and regulations. 52.133 Section 52.133 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Arizona § 52.133 Rules and regulations. (a) Regulation 7...
Li, Luowei; Sampat, Keeran; Hu, Nancy; Zakari, Julia; Yuspa, Stuart H
2006-02-10
Skin keratinocytes are subject to frequent chemical and physical injury and have developed elaborate cell survival mechanisms to compensate. Among these, the Akt/protein kinase B (PKB) pathway protects keratinocytes from the toxic effects of ultraviolet light (UV). In contrast, the protein kinase C (PKC) family is involved in several keratinocyte death pathways. During an examination of potential interactions among these two pathways, we found that the insulin-like growth factor (IGF-1) activates both the PKC and the Akt signaling pathways in cultured primary mouse keratinocytes as indicated by increased phospho-PKC and phospho-Ser-473-Akt. IGF-1 also selectively induced translocation of PKCdelta and PKCepsilon from soluble to particulate fractions in mouse keratinocytes. Furthermore, the PKC-specific inhibitor, GF109203X, increased IGF-1-induced phospho-Ser-473-Akt and Akt kinase activity and enhanced IGF-1 protection from UVC-induced apoptosis. Selective activation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) reduced phospho-Ser-473-Akt, suggesting that activation of PKC inhibits Akt activity. TPA also attenuated IGF-1 and epidermal growth factor-induced phospho-Ser-473-Akt, reduced Akt kinase activity, and blocked IGF-1 protection from UVC-induced apoptosis. The inhibition of Akt activity by TPA was reduced by inhibitors of protein phosphatase 2A, and TPA stimulated the association of phosphatase 2A with Akt. Individual PKC isoforms were overexpressed in cultured keratinocytes by transduction with adenoviral vectors or inhibited with PKC-selective inhibitors. These studies indicated that PKCdelta and PKCepsilon were selectively potent at causing dephosphorylation of Akt and modifying cell survival, whereas PKCalpha enhanced phosphorylation of Akt on Ser-473. Our results suggested that activation of PKCdelta and PKCepsilon provide a negative regulation for Akt phosphorylation and kinase activity in mouse keratinocytes and serve as modulators of cell survival pathways in response to external stimuli.
10 CFR 20.2007 - Compliance with environmental and health protection regulations.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 10 Energy 1 2013-01-01 2013-01-01 false Compliance with environmental and health protection regulations. 20.2007 Section 20.2007 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2007 Compliance with environmental and health protection regulations. Nothing...
10 CFR 20.2007 - Compliance with environmental and health protection regulations.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 10 Energy 1 2014-01-01 2014-01-01 false Compliance with environmental and health protection regulations. 20.2007 Section 20.2007 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2007 Compliance with environmental and health protection regulations. Nothing...
10 CFR 20.2007 - Compliance with environmental and health protection regulations.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 10 Energy 1 2010-01-01 2010-01-01 false Compliance with environmental and health protection regulations. 20.2007 Section 20.2007 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2007 Compliance with environmental and health protection regulations. Nothing...
10 CFR 20.2007 - Compliance with environmental and health protection regulations.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 10 Energy 1 2011-01-01 2011-01-01 false Compliance with environmental and health protection regulations. 20.2007 Section 20.2007 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2007 Compliance with environmental and health protection regulations. Nothing...
10 CFR 20.2007 - Compliance with environmental and health protection regulations.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 10 Energy 1 2012-01-01 2012-01-01 false Compliance with environmental and health protection regulations. 20.2007 Section 20.2007 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2007 Compliance with environmental and health protection regulations. Nothing...
Jones, D C; Abbey, B B; Cumberland, A
1998-08-01
The development of display rule knowledge and its associations with family expressiveness (Study 1) and peer competence (Study 2) were investigated among elementary school children. In Study 1, the display rule knowledge of 121 kindergartners and third graders was assessed using validated hypothetical scenarios. There were significant grade differences in display rule knowledge such that third graders compared to kindergartners more frequently combined expression regulation with prosocial reasoning, norm-maintenance, and self-protective motives. Maternal reports of family emotional climates indicated that aspects of negative expressiveness were related positively to self-protective display rules and negatively to prosocial display rules. Study 2 included 93 third and fifth graders who reported on their display rule knowledge and on their emotional reactions and strategies to resolve peer conflict. Classmates and teachers provided ratings on social competence. Age differences for display rule knowledge were not documented, but prosocial display rules were most consistently related to hypothetical peer conflict responses and social competence. The findings confirm that display rule knowledge is related in consistent and systematic ways to what children learn within the family emotional context, how they propose to resolve peer conflict, and how they are perceived by peers and teachers.
Negative Regulation of Violacein Biosynthesis in Chromobacterium violaceum
Devescovi, Giulia; Kojic, Milan; Covaceuszach, Sonia; Cámara, Miguel; Williams, Paul; Bertani, Iris; Subramoni, Sujatha; Venturi, Vittorio
2017-01-01
In Chromobacteium violaceum, the purple pigment violacein is under positive regulation by the N-acylhomoserine lactone CviI/R quorum sensing system and negative regulation by an uncharacterized putative repressor. In this study we report that the biosynthesis of violacein is negatively controlled by a novel repressor protein, VioS. The violacein operon is regulated negatively by VioS and positively by the CviI/R system in both C. violaceum and in a heterologous Escherichia coli genetic background. VioS does not regulate the CviI/R system and apart from violacein, VioS, and quorum sensing regulate other phenotypes antagonistically. Quorum sensing regulated phenotypes in C. violaceum are therefore further regulated providing an additional level of control. PMID:28326068
Singh, Preeti; Hanson, Peter S; Morris, Christopher M
2017-06-02
Sirtuins (SIRTs) are NAD + dependent lysine deacetylases which are conserved from bacteria to humans and have been associated with longevity and lifespan extension. SIRT1, the best studied mammalian SIRT is involved in many physiological and pathological processes and changes in SIRT1 have been implicated in neurodegenerative disorders, with SIRT1 having a suggested protective role in Parkinson's disease. In this study, we determined the effect of SIRT1 on cell survival and α-synuclein aggregate formation in SH-SY5Y cells following oxidative stress. Over-expression of SIRT1 protected SH-SY5Y cells from toxin induced cell death and the protection conferred by SIRT1 was partially independent of its deacetylase activity, which was associated with the repression of NF-кB and cPARP expression. SIRT1 reduced the formation of α-synuclein aggregates but showed minimal co-localisation with α-synuclein. In post-mortem brain tissue obtained from patients with Parkinson's disease, Parkinson's disease with dementia, dementia with Lewy bodies and Alzheimer's disease, the activity of SIRT1 was observed to be down-regulated. These findings suggests a negative effect of oxidative stress in neurodegenerative disorders and possibly explain the reduced activity of SIRT1 in neurodegenerative disorders. Our study shows that SIRT1 is a pro-survival protein that is downregulated under cellular stress.
Poon, Kinning; Alam, Mohammad; Karatayev, Olga; Barson, Jessica R; Leibowitz, Sarah F
2015-12-01
Ingestion of a high-fat diet composed mainly of the saturated fatty acid, palmitic (PA), and the unsaturated fatty acid, oleic (OA), stimulates transcription in the brain of the opioid neuropeptide, enkephalin (ENK), which promotes intake of substances of abuse. To understand possible underlying mechanisms, this study examined the nuclear receptors, peroxisome proliferator-activated receptors (PPARs), and tested in hypothalamic and forebrain neurons from rat embryos whether PPARs regulate endogenous ENK and the fatty acids themselves affect these PPARs and ENK. The first set of experiments demonstrated that knocking down PPARδ, but not PPARα or PPARγ, increased ENK transcription, activation of PPARδ by an agonist decreased ENK levels, and PPARδ neurons coexpressed ENK, suggesting that PPARδ negatively regulates ENK. In the second set of experiments, PA treatment of hypothalamic and forebrain neurons had no effect on PPARδ protein while stimulating ENK mRNA and protein, whereas OA increased both mRNA and protein levels of PPARδ in forebrain neurons while having no effect on ENK mRNA and increasing ENK levels. These findings show that PA has a strong, stimulatory effect on ENK and weak effect on PPARδ protein, whereas OA has a strong stimulatory effect on PPARδ and weak effect on ENK, consistent with the inhibitory effect of PPARδ on ENK. They suggest a function for PPARδ, perhaps protective in nature, in embryonic neurons exposed to fatty acids from a fat-rich diet and provide evidence for a mechanism contributing to differential effects of saturated and monounsaturated fatty acids on neurochemical systems involved in consummatory behavior. Our findings show that PPARδ in forebrain and hypothalamic neurons negatively regulates enkephalin (ENK), a peptide known to promote ingestive behavior. This inverse relationship is consistent with our additional findings, that a saturated (palmitic; PA) compared to a monounsaturated fatty acid (oleic; OA) has a strong stimulatory effect on ENK and weak effect on PPARδ. These results suggest that PPARδ protects against the neuronal effects of fatty acids, which differentially affect neurochemical systems involved in ingestive behavior. © 2015 International Society for Neurochemistry.
Wang, Shuyi; Chen, Xiyao; Nair, Sreejayan; Sun, Dongdong; Wang, Xiaoming; Ren, Jun
2017-12-01
Endoplasmic reticulum (ER) stress has been demonstrated to prompt various cardiovascular risks although the underlying mechanism remains elusive. Protein tyrosine phosphatase-1B (PTP1B) serves as an essential negative regulator for insulin signaling. This study examined the role of PTP1B in ER stress-induced myocardial anomalies and underlying mechanism involved with a focus on autophagy. WT and PTP1B knockout mice were subjected to the ER stress inducer tunicamycin (1mg/kg). Cardiac function was evaluated with echocardiography and an Ion-Optix MyoCam system. Western blot analysis was used to monitor the levels of ER stress, autophagy and insulin signaling including insulin receptor substrate (IRS), tribbles homolog 3 (TRIB3), Atg5/7, p62 and LC3-II. Our results showed that ER stress resulted in compromised echocardiographic and cardiomyocyte contractile function, intracellular Ca 2+ mishandling, ER stress, O 2 - production, apoptosis, the effects of which (with the exception of ER stress) were significantly attenuated or negated by PTP1B ablation. Levels of serine phosphorylation of IRS-1, TRIB3, Atg5/7, LC3B and the autophagy adaptor p62 were significantly upregulated while IRS-1 tyrosine phosphorylation was reduced by tunicamycin, the effect of which were obliterated by PTP1B ablation. In vitro study revealed that the autophagy inducer rapamycin and TRIB3 overexpression cancelled PTP1B ablation-offered beneficial effects on cardiomyocyte function or O 2 - production in murine cardiomyocytes or H9C2 myoblasts. Antioxidant or gene silencing of TRIB3 mimicked PTP1B ablation-induced protective effects. These findings collectively suggested that PTP1B ablation protects against ER stress-induced cardiac anomalies through regulation of autophagy. Copyright © 2017 Elsevier B.V. All rights reserved.
Yu, Cheng-Rong; Kim, Sung-Hye; Mahdi, Rashid M; Egwuagu, Charles E
2013-11-15
Suppressors of cytokine signaling (SOCS) proteins are negative-feedback regulators of the JAK/STAT pathway, and SOCS3 contributes to host immunity by regulating the intensity and duration of cytokine signals and inflammatory responses. Mice with Socs3 deletion in myeloid cells exhibit enhanced STAT3 signaling, expansion of Th1 and Th17 cells, and develop severe experimental autoimmune encephalomyelitis. Interestingly, development of the unique IL-17/IFN-γ double-producing (Th17/IFN-γ and Tc17/IFN-γ) subsets that exhibit strong cytotoxic activities and are associated with pathogenesis of several autoimmune diseases has recently been shown to depend on epigenetic suppression of SOCS3 expression, further suggesting involvement of SOCS3 in autoimmunity and tumor immunity. In this study, we generated mice with Socs3 deletion in the CD4 T cell compartment (CD4-SOCS3 knockout [KO]) to determine in vivo effects of the loss of Socs3 in the T cell-mediated autoimmune disease, experimental autoimmune uveitis (EAU). In contrast to the exacerbation of experimental autoimmune encephalomyelitis in myeloid-specific SOCS3-deleted mice, CD4-SOCS3KO mice were protected from acute and chronic uveitis. Protection from EAU correlated with enhanced expression of CTLA-4 and expansion of IL-10-producing regulatory T cells with augmented suppressive activities. We further show that SOCS3 interacts with CTLA-4 and negatively regulates CTLA-4 levels in T cells, providing a mechanistic explanation for the expansion of regulatory T cells in CD4-SOCS3 during EAU. Contrary to in vitro epigenetic studies, Th17/IFN-γ and Tc17/IFN-γ populations were markedly reduced in CD4-SOCS3KO, suggesting that SOCS3 promotes expansion of the Th17/IFN-γ subset associated with development of severe uveitis. Thus, SOCS3 is a potential therapeutic target in uveitis and other autoinflammatory diseases.
48 CFR 225.7403 - Antiterrorism/force protection.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Antiterrorism/force protection. 225.7403 Section 225.7403 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS... United States 225.7403 Antiterrorism/force protection. ...
Eisenberg, N; Fabes, R A; Karbon, M; Murphy, B C; Wosinski, M; Polazzi, L; Carlo, G; Juhnke, C
1996-06-01
The purpose of this study was to examine the relations of a measure of children's dispositional prosocial behavior (i.e., peer nominations) to individual differences in children's negative emotionality, regulation, and social functioning. Children with prosocial reputations tended to be high in constructive social skills (i.e., socially appropriate behavior and constructive coping) and attentional regulation, and low in negative emotionality. The relations of children's negative emotionality to prosocial reputation were moderated by level of dispositional attentional regulation. In addition, the relations of prosocial reputation to constructive social skills and parent-reported negative emotionality (for girls) increased with age. Vagal tone, a marker of physiological regulation, was negatively related to girls' prosocial reputation.
Artuch-Garde, Raquel; González-Torres, Maria del Carmen; de la Fuente, Jesús; Vera, M. Mariano; Fernández-Cabezas, María; López-García, Mireia
2017-01-01
The ability to self-regulate behavior is one of the most important protective factors in relation with resilience and should be fostered especially in at-risk youth. Previous research has characterized these students as having behaviors indicating lack of foresight. The aim of the present study was to test the hypothetical relationship between these personal variables. It was hypothesized that self-regulation would be associated with and would be a good predictor of resilience, and that low-medium-high levels of self-regulation would lead to similar levels of resilience. The participants were 365 students -aged 15 and 21- from Navarre (Spain) who were enrolled in Initial Vocational Qualification Programs (IVQP). For the assessment, the Connor Davidson Resilience Scale (CD-RISC) and the Short Self-Regulation Questionnaire (SSRQ) were applied. We carried out linear association analyses (correlational and structural) and non-linear interdependence analyses (MANOVA) between the two constructs. Relationships between them were significant and positive. Learning from mistakes (self-regulation) was a significant predictor of coping and confidence, tenacity and adaptation, and tolerance to negative situations (resilience). Likewise, low-medium-high levels of self-regulation correlated with scores on resilience factors. Implications of these results for educational practice and for future research are discussed. PMID:28473792
40 CFR 62.9515 - Identification of sources-Negative declaration.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources-Negative declaration. 62.9515 Section 62.9515 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Oregon Metals, Acid Gases, Organic Compounds, Particulates and Nitrogen Oxide Emissions from Existing...
Santander, Ricardo D; Monte-Serrano, Mercedes; Rodríguez-Herva, José J; López-Solanilla, Emilia; Rodríguez-Palenzuela, Pablo; Biosca, Elena G
2014-12-01
Erwinia amylovora causes fire blight in economically important plants of the family Rosaceae. This bacterial pathogen spends part of its life cycle coping with starvation and other fluctuating environmental conditions. In many Gram-negative bacteria, starvation and other stress responses are regulated by the sigma factor RpoS. We obtained an E. amylovora rpoS mutant to explore the role of this gene in starvation responses and its potential implication in other processes not yet studied in this pathogen. Results showed that E. amylovora needs rpoS to develop normal starvation survival and viable but nonculturable (VBNC) responses. Furthermore, this gene contributed to stationary phase cross-protection against oxidative, osmotic, and acid stresses and was essential for cross-protection against heat shock, but nonessential against acid shock. RpoS also mediated regulation of motility, exopolysaccharide synthesis, and virulence in immature loquats, but not in pear plantlets, and contributed to E. amylovora survival in nonhost tissues during incompatible interactions. Our results reveal some unique roles for the rpoS gene in E. amylovora and provide new knowledge on the regulation of different processes related to its ecology, including survival in different environments and virulence in immature fruits. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.
Zeng, Ke-Wu; Liao, Li-Xi; Zhao, Ming-Bo; Song, Fang-Jiao; Yu, Qian; Jiang, Yong; Tu, Peng-Fei
2015-03-15
Protosappanin B (PTB) is a bioactive dibenzoxocin derivative isolated from Caesalpinia sappan L. Here, we investigated the neuroprotective effects and the potential mechanisms of PTB on oxygen-glucose deprivation (OGD)-injured PC12 cells. Results showed that PTB significantly increased cell viability, inhibited cell apoptosis and up-regulated the expression of growth-associated protein 43 (a marker of neural outgrowth). Moreover, our study revealed that PTB effectively maintained mitochondrial homeostasis by up-regulation of mitochondrial membrane potential (MMP), inhibition of cytochrome c release from mitochondria and inactivation of mitochondrial caspase-9/3 apoptosis pathway. Further study showed that PTB significantly promoted cytoplasmic component degradation of p53 protein, a key negative regulator for mitochondrial function, resulting in a release of Bcl-2 from p53-Bcl-2 complex and an enhancing translocation of Bcl-2 to mitochondrial outer membrane. Finally, we found the degradation of p53 protein was induced by PTB via activation of a MDM2-dependent ubiquitination process. Taken together, our findings provided a new viewpoint of neuronal protection strategy for anoxia and ischemic injury with natural small molecular dibenzoxocin derivative by activating ubiquitin-dependent p53 protein degradation as well as increasing mitochondrial function. Copyright © 2015 Elsevier B.V. All rights reserved.
TRIM21 ubiquitylates SQSTM1/p62 and suppresses protein sequestration to regulate redox homeostasis
Pan, Ji-An; Sun, Yu; Jiang, Ya-Ping; Bott, Alex J.; Jaber, Nadia; Dou, Zhixun; Yang, Bin; Chen, Juei-Suei; Catanzaro, Joseph M.; Du, Chunying; Ding, Wen-Xing; Diaz-Meco, Maria T.; Moscat, Jorge; Ozato, Keiko; Lin, Richard Z.; Zong, Wei-Xing
2016-01-01
Summary TRIM21 is a RING finger domain-containing ubiquitin E3 ligase whose expression is elevated in autoimmune disease. While TRIM21 plays an important role in immune activation during pathogen infection, little is known about its inherent cellular function. Here we show that TRIM21 plays an essential role in redox regulation by directly interacting with SQSTM1/p62 and ubiquitylating p62 at lysine(K)7 via K63-linkage. As p62 oligomerizes and sequesters client proteins in inclusions, the TRIM21-mediated p62 ubiquitylation abrogates p62 oligomerization and sequestration of proteins including Keap1, a negative regulator of antioxidant response. TRIM21-deficient cells display an enhanced antioxidant response and reduced cell death in response to oxidative stress. Genetic ablation of TRIM21 in mice confers protection from oxidative damages caused by arsenic-induced liver insult and pressure overload heart injury. Therefore, TRIM21 plays an essential role in p62-regulated redox homeostasis and may be a viable target for treating pathological conditions resulting from oxidative damage. PMID:26942676
FOXO1 promotes wound healing through the up-regulation of TGF-β1 and prevention of oxidative stress
Ponugoti, Bhaskar; Xu, Fanxing; Zhang, Chenying; Tian, Chen; Pacios, Sandra
2013-01-01
Keratinocyte mobilization is a critical aspect of wound re-epithelialization, but the mechanisms that control its precise regulation remain poorly understood. We set out to test the hypothesis that forkhead box O1 (FOXO1) has a negative effect on healing because of its capacity to inhibit proliferation and promote apoptosis. Contrary to expectations, FOXO1 is required for keratinocyte transition to a wound-healing phenotype that involves increased migration and up-regulation of transforming growth factor β1 (TGF-β1) and its downstream targets, integrin-α3 and -β6 and MMP-3 and -9. Furthermore, we show that FOXO1 functions in keratinocytes to reduce oxidative stress, which is necessary to maintain cell migration and prevent cell death in a TGF-β1–independent manner. Thus, our studies identify a novel function for FOXO1 in coordinating the response of keratinocytes to wounding through up-regulation of TGF-β1 and other factors needed for keratinocyte migration and protection against oxidative stress, which together promote migration and decrease apoptosis. PMID:24145170
TRIM21 Ubiquitylates SQSTM1/p62 and Suppresses Protein Sequestration to Regulate Redox Homeostasis.
Pan, Ji-An; Sun, Yu; Jiang, Ya-Ping; Bott, Alex J; Jaber, Nadia; Dou, Zhixun; Yang, Bin; Chen, Juei-Suei; Catanzaro, Joseph M; Du, Chunying; Ding, Wen-Xing; Diaz-Meco, Maria T; Moscat, Jorge; Ozato, Keiko; Lin, Richard Z; Zong, Wei-Xing
2016-03-03
TRIM21 is a RING finger domain-containing ubiquitin E3 ligase whose expression is elevated in autoimmune disease. While TRIM21 plays an important role in immune activation during pathogen infection, little is known about its inherent cellular function. Here we show that TRIM21 plays an essential role in redox regulation by directly interacting with SQSTM1/p62 and ubiquitylating p62 at lysine 7 (K7) via K63-linkage. As p62 oligomerizes and sequesters client proteins in inclusions, the TRIM21-mediated p62 ubiquitylation abrogates p62 oligomerization and sequestration of proteins including Keap1, a negative regulator of antioxidant response. TRIM21-deficient cells display an enhanced antioxidant response and reduced cell death in response to oxidative stress. Genetic ablation of TRIM21 in mice confers protection from oxidative damages caused by arsenic-induced liver insult and pressure overload heart injury. Therefore, TRIM21 plays an essential role in p62-regulated redox homeostasis and may be a viable target for treating pathological conditions resulting from oxidative damage. Copyright © 2016 Elsevier Inc. All rights reserved.
Lee, Hyoung S.; Catley, Delwyn; Harris, Kari Jo
2011-01-01
This study compared autonomous self-regulation and negative self-evaluative emotions as predictors of smoking behavior change in college student smokers (N=303) in a smoking cessation intervention study. Although the two constructs were moderately correlated, latent growth curve modeling revealed that only autonomous regulation, but not negative self-evaluative emotions, was negatively related to the number of days smoked. Results suggest that the two variables tap different aspects of motivation to change smoking behaviors, and that autonomous regulation predicts smoking behavior change better than negative self-evaluative emotions. PMID:21911436
Lee, Hyoung S; Catley, Delwyn; Harris, Kari Jo
2012-05-01
This study compared autonomous self-regulation and negative self-evaluative emotions as predictors of smoking behavior change in college student smokers (N = 303) in a smoking cessation intervention study. Although the two constructs were moderately correlated, latent growth curve modeling revealed that only autonomous regulation, but not negative self-evaluative emotions, was negatively related to the number of days smoked. Results suggest that the two variables tap different aspects of motivation to change smoking behaviors, and that autonomous regulation predicts smoking behavior change better than negative self-evaluative emotions.
Bao, Chengzhen; Chai, Pengfei; Lin, Hongbo; Zhang, Zhenyu; Ye, Zhenhua; Gu, Mengjia; Lu, Huaichu; Shen, Peng; Jin, Mingjuan; Wang, Jianbing; Chen, Kun
2016-12-01
Recently, air pollution has attracted a substantial amount of attention in China, which can be influenced by a variety of factors, but the association between air pollution and human activity is not quite clear. Based on real-time online data (January 1, 2014, to December 31, 2014) of air pollution and meteorology reported by official sites, and demographic, economic, and environmental reform data in a statistical yearbook, the influences of meteorological factors (temperature, relative humidity, precipitation intensity, and wind force) and human activities on PM 2.5 pollution were explored. After correlation analysis, logistic regression analysis, and a nonparametric test, weak negative correlations between temperature and PM 2.5 pollution were found. In most cases, festival and morning peak hours were protection and risk factors of PM 2.5 pollution, respectively. In addition, government actions, such as an afforestation project and increasing financial expenditure for energy saving and environmental protection, could greatly contribute to alleviating pollution of PM 2.5 . The findings could help officials formulate effective laws and regulations, and then PM 2.5 pollution related to the pattern of human activity would be ameliorated. Most of the time, festival and morning peak hours are protection and risk factors for PM 2.5 pollution, respectively. Increasing the percentage of afforestation area and financial expenditure for energy saving and environmental protection could significantly reduce PM 2.5 pollution. The findings can help officials formulate effective laws and regulations, and then PM 2.5 pollution related to the pattern of human activity, especially government action, will be ameliorated.
Pesant, Matthieu; Sueur, Stéphanie; Dutartre, Patrick; Tallandier, Mireille; Grimaldi, Paul A; Rochette, Luc; Connat, Jean-Louis
2006-02-01
Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma plays beneficial roles in cardiovascular disorders such as atherosclerosis and heart reperfusion. Although PPARalpha and gamma have been documented to reduce oxidative stress in the vasculature and the heart, the role of PPARdelta remains poorly studied. We focused on PPARdelta function in the regulation of oxidative stress-induced apoptosis in the rat cardiomyoblast cell line H9c2. Using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we showed that PPARdelta is the predominantly expressed isotype whereas PPARalpha was weakly detected. By performing cell viability assays, we also showed that the selective PPARdelta agonist GW501516 protected cells from H(2)O(2)-induced cell death. The protective effect of GW501516 was due to an inhibition of H(2)O(2)-triggered apoptosis as shown by annexin-V labeling, DNA fragmentation analysis, and caspase-3 activity measurement. We demonstrated by transient transfection of a dominant negative mutant of PPARdelta that the protection induced by GW501516 was totally dependent on PPARdelta. Semi-quantitative RT-PCR and Western blotting analysis demonstrated that GW501516 treatment upregulated catalase. Moreover, forced overexpression of catalase inhibited H(2)O(2)-triggered apoptosis, as evidenced by annexin-V labeling. Taken together, our results account for an important role of PPARdelta in inhibiting the onset of oxidative stress-induced apoptosis in H9c2 cells. PPARdelta appears to be a new therapeutic target for the regulation of heart reperfusion-associated oxidative stress and stimulation of enzymatic antioxidative defences.
Rebmann, Terri
2005-12-01
Many US hospitals lack the capacity to house safely a surge of potentially infectious patients, increasing the risk of secondary transmission. Respiratory protection and negative-pressure rooms are needed to prevent transmission of airborne-spread diseases, but US hospitals lack available and/or properly functioning negative-pressure rooms. Creating new rooms or retrofitting existing facilities is time-consuming and expensive. Safe methods of managing patients with airborne-spread diseases and establishing temporary negative-pressure and/or protective environments were determined by a literature review. Relevant data were analyzed and synthesized to generate a response algorithm. Ideal patient management and placement guidelines, including instructions for choosing respiratory protection and creating temporary negative-pressure or other protective environments, were delineated. Findings were summarized in a treatment algorithm. The threat of bioterrorism and emerging infections increases health care's need for negative-pressure and/or protective environments. The algorithm outlines appropriate response steps to decrease transmission risk until an ideal protective environment can be utilized. Using this algorithm will prepare infection control professionals to respond more effectively during a surge of potentially infectious patients following a bioterrorism attack or emerging infectious disease outbreak.
Khosravani, Vahid; Sharifi Bastan, Farangis; Ghorbani, Fatemeh; Kamali, Zoleikha
2017-08-01
The aim of this study was to assess the mediating effects of difficulties in emotion regulation (DER) on the relations of negative and positive affects to craving in alcoholic patients. 205 treatment-seeking alcoholic outpatients were included. DER, positive and negative affects as well as craving were evaluated by the Difficulties in Emotion Regulation Scale (DERS), the Positive/Negative Affect Scales, and the Obsessive Compulsive Drinking Scale (OCDS) respectively. Clinical factors including depression and severity of alcohol dependence were investigated by the Alcohol Use Disorders Identification Test (AUDIT) and the Beck Depression Inventory-II (BDI-II) respectively. Results revealed that both increased negative affect and decreased positive affect indirectly influenced craving through limited access to emotion regulation strategies. It was concluded that limited access to emotion regulation strategies may be important in predicting craving for alcoholics who experience both increased negative affect and decreased positive affect. This suggests that treatment and prevention efforts focused on increasing positive affect, decreasing negative affect and teaching effective regulation strategies may be critical in reducing craving in alcoholic patients. Copyright © 2017 Elsevier Ltd. All rights reserved.
Nguyen, Kien Huu; Ha, Chien Van; Nishiyama, Rie; Watanabe, Yasuko; Leyva-González, Marco Antonio; Fujita, Yasunari; Tran, Uven Thi; Li, Weiqiang; Tanaka, Maho; Seki, Motoaki; Schaller, G. Eric; Herrera-Estrella, Luis; Tran, Lam-Son Phan
2016-01-01
In this study, we used a loss-of-function approach to elucidate the functions of three Arabidopsis type B response regulators (ARRs)—namely ARR1, ARR10, and ARR12—in regulating the Arabidopsis plant responses to drought. The arr1,10,12 triple mutant showed a significant increase in drought tolerance versus WT plants, as indicated by its higher relative water content and survival rate on drying soil. This enhanced drought tolerance of arr1,10,12 plants can be attributed to enhanced cell membrane integrity, increased anthocyanin biosynthesis, abscisic acid (ABA) hypersensitivity, and reduced stomatal aperture, but not to altered stomatal density. Further drought-tolerance tests of lower-order double and single mutants indicated that ARR1, ARR10, and ARR12 negatively and redundantly control plant responses to drought, with ARR1 appearing to bear the most critical function among the three proteins. In agreement with these findings, a comparative genome-wide analysis of the leaves of arr1,10,12 and WT plants under both normal and dehydration conditions suggested a cytokinin (CK) signaling-mediated network controlling plant adaptation to drought via many dehydration/drought- and/or ABA-responsive genes that can provide osmotic adjustment and protection to cellular and membrane structures. Expression of all three ARR genes was repressed by dehydration and ABA treatments, inferring that plants down-regulate these genes as an adaptive mechanism to survive drought. Collectively, our results demonstrate that repression of CK response, and thus CK signaling, is one of the strategies plants use to cope with water deficit, providing novel insight for the design of drought-tolerant plants by genetic engineering. PMID:26884175
Nguyen, Kien Huu; Ha, Chien Van; Nishiyama, Rie; Watanabe, Yasuko; Leyva-González, Marco Antonio; Fujita, Yasunari; Tran, Uven Thi; Li, Weiqiang; Tanaka, Maho; Seki, Motoaki; Schaller, G Eric; Herrera-Estrella, Luis; Tran, L S
2016-03-15
In this study, we used a loss-of-function approach to elucidate the functions of three Arabidopsis type B response regulators (ARRs)--namely ARR1, ARR10, and ARR12--in regulating the Arabidopsis plant responses to drought. The arr1,10,12 triple mutant showed a significant increase in drought tolerance versus WT plants, as indicated by its higher relative water content and survival rate on drying soil. This enhanced drought tolerance of arr1,10,12 plants can be attributed to enhanced cell membrane integrity, increased anthocyanin biosynthesis, abscisic acid (ABA) hypersensitivity, and reduced stomatal aperture, but not to altered stomatal density. Further drought-tolerance tests of lower-order double and single mutants indicated that ARR1, ARR10, and ARR12 negatively and redundantly control plant responses to drought, with ARR1 appearing to bear the most critical function among the three proteins. In agreement with these findings, a comparative genome-wide analysis of the leaves of arr1,10,12 and WT plants under both normal and dehydration conditions suggested a cytokinin (CK) signaling-mediated network controlling plant adaptation to drought via many dehydration/drought- and/or ABA-responsive genes that can provide osmotic adjustment and protection to cellular and membrane structures. Expression of all three ARR genes was repressed by dehydration and ABA treatments, inferring that plants down-regulate these genes as an adaptive mechanism to survive drought. Collectively, our results demonstrate that repression of CK response, and thus CK signaling, is one of the strategies plants use to cope with water deficit, providing novel insight for the design of drought-tolerant plants by genetic engineering.
Hugo, Carina Jacobie; van der Merwe, Mariette
2014-01-01
This qualitative case study explored risk factors and protective factors in the bio-psychosocial fields of adolescents living with cystic fibrosis (CF). Semi-structured interviews were conducted with adolescents in the middle and late adolescent years (15-22 years) who had the defining characteristics of CF and were living in Gauteng province. Themes emerged from individual interviews. The fundamental human need to be understood and to understand was negatively affected as the illness affected socialisation and learning. Participants experienced an array of emotions including loss and bereavement linked to their illness and when friends with CF died. Constructive internal dialogue and positive thinking emerged as protective variables. Participants generally showed awareness of how they regulated their contact with the illness and how they self-regulate. Despite the severity of their symptoms and the taxing demands of managing CF, participants expressed hope for the future and could find some meaning in the illness. Adolescents with CF who participated in this study indicated that they felt different from their peers. Apart from the general developmental tasks typical to adolescence they faced the challenge of managing a severe chronic and potentially terminal illness.
The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+ T cells.
Moalli, Federica; Ficht, Xenia; Germann, Philipp; Vladymyrov, Mykhailo; Stolp, Bettina; de Vries, Ingrid; Lyck, Ruth; Balmer, Jasmin; Fiocchi, Amleto; Kreutzfeldt, Mario; Merkler, Doron; Iannacone, Matteo; Ariga, Akitaka; Stoffel, Michael H; Sharpe, James; Bähler, Martin; Sixt, Michael; Diz-Muñoz, Alba; Stein, Jens V
2018-06-06
T cells are actively scanning pMHC-presenting cells in lymphoid organs and nonlymphoid tissues (NLTs) with divergent topologies and confinement. How the T cell actomyosin cytoskeleton facilitates this task in distinct environments is incompletely understood. Here, we show that lack of Myosin IXb (Myo9b), a negative regulator of the small GTPase Rho, led to increased Rho-GTP levels and cell surface stiffness in primary T cells. Nonetheless, intravital imaging revealed robust motility of Myo9b -/- CD8 + T cells in lymphoid tissue and similar expansion and differentiation during immune responses. In contrast, accumulation of Myo9b -/- CD8 + T cells in NLTs was strongly impaired. Specifically, Myo9b was required for T cell crossing of basement membranes, such as those which are present between dermis and epidermis. As consequence, Myo9b -/- CD8 + T cells showed impaired control of skin infections. In sum, we show that Myo9b is critical for the CD8 + T cell adaptation from lymphoid to NLT surveillance and the establishment of protective tissue-resident T cell populations. © 2018 Moalli et al.
Fu, Bi-Cheng; Lang, Ji-Lu; Zhang, Dong-Yang; Sun, Lu; Chen, Wei; Liu, Wei; Liu, Kai-Yu; Ma, Chong-Yi; Jiang, Shu-Lin; Li, Ren-Ke; Tian, Hai
2017-09-01
MicroRNA-34a (miR-34a) is expressed in the myocardium and expression is altered after myocardial injury. We investigated the effects of miR-34a on heart function after ischemia-reperfusion (IR) injury. Cardiomyocytes were isolated from neonatal rat hearts and simulated IR injury was induced in vitro. Following IR injury in rats, infarct size was measured and left ventricular (LV) function was evaluated using echocardiography. Protein expression of silent information regulator 1 (SIRT1), acetylated p53 (ac-p53), Bcl-2 and Bax, and miR-34a and SIRT1 gene levels were analyzed. miR-34a overexpression exacerbated myocardial injury by increasing apoptosis and infarct size and decreasing LV function. Suppression of miR-34a attenuated myocardial IR injury. SIRT1 was negatively regulated by miR-34a and the expression of downstream genes, such as ac-p53, Bcl-2, and Bax were altered correspondingly. Increased expression of miR-34a aggravates injury after IR; miR-34a suppression therapy may represent a new line of treatment for myocardial IR injury.
40 CFR 62.5400 - Identification of plan-negative declaration.
Code of Federal Regulations, 2010 CFR
2010-07-01
... declaration. The State Department of Environmental Quality Engineering submitted on January 18, 1989, a letter... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of plan-negative declaration. 62.5400 Section 62.5400 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...
40 CFR 62.5350 - Identification of plan-negative declaration.
Code of Federal Regulations, 2010 CFR
2010-07-01
... declaration. The State Department of Environmental Quality Engineering submitted on April 12, 1978, a letter... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of plan-negative declaration. 62.5350 Section 62.5350 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...
The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity
Chan, Pamela Y.; Carrera Silva, Eugenio A.; De Kouchkovsky, Dimitri; Joannas, Leonel D.; Hao, Liming; Hu, Donglei; Huntsman, Scott; Eng, Celeste; Licona-Limón, Paula; Weinstein, Jason S.; Herbert, De’Broski R.; Craft, Joseph E.; Flavell, Richard A.; Repetto, Silvia; Correale, Jorge; Burchard, Esteban G.; Torgerson, Dara G.; Ghosh, Sourav; Rothlin, Carla V.
2016-01-01
Host responses against metazoan parasites or an array of environmental substances elicit type 2 immunity. Despite its protective function, type 2 immunity also drives allergic diseases. The mechanisms that regulate the magnitude of the type 2 response remain largely unknown. Here, we show that genetic ablation of a receptor tyrosine kinase encoded by Tyro3 in mice or the functional neutralization of its ortholog in human dendritic cells resulted in enhanced type 2 immunity. Furthermore, the TYRO3 agonist PROS1 was induced in T cells by the quintessential type 2 cytokine, interleukin-4. T cell–specific Pros1 knockouts phenocopied the loss of Tyro3. Thus, a PROS1-mediated feedback from adaptive immunity engages a rheostat, TYRO3, on innate immune cells to limit the intensity of type 2 responses. PMID:27034374
Mother-child language style matching predicts children's and mothers' emotion reactivity.
Rasmussen, Hannah F; Borelli, Jessica L; Smiley, Patricia A; Cohen, Chloe; Cheung, Ryan Cheuk Ming; Fox, Schuyler; Marvin, Matthew; Blackard, Betsy
2017-05-15
Co-regulation of behavior occurring within parent-child attachment relationships is thought to be the primary means through which children develop the capacity to regulate emotion, an ability that is protective across development. Existing research on parent-child co-regulation focuses predominantly on parent-infant dyads, and operationalizes co-regulation as the matching of facial expressions; however, matching can occur on other behaviors, including vocal tone, body movement, and language. Studies with young children find that greater matching is associated with children's lower emotion reactivity, but with unknown impacts on parents. In this study we examine a recently-developed metric of behavioral matching, language style matching (LSM), a composite measure of the similarity of function word use in spoken or written language between two or more people. We test whether LSM between mothers and their school-aged children is associated with children's and mothers' physiological and subjective emotion reactivity. Children completed a standardized stressor task while their mothers observed; children's and mother's cortisol and cardiovascular reactivity were assessed, as were their subjective reports of emotion reactivity. Following the stressor, children and mothers completed independent interviews about the experience, later assessed for LSM. Higher mother-child LSM was associated with lower emotion reactivity (lower cortisol reactivity, lower reports of negative emotion) for children, and with higher maternal cardiovascular but not cortisol or subjective reactivity. Further, higher LSM was more strongly associated with lower child cortisol reactivity when mothers were more reactive themselves. We conclude that mother-child LSM, thought to reflect a history of co-regulated interaction, confers protective benefits for children, but heightened reactivity for mothers. Copyright © 2016 Elsevier B.V. All rights reserved.
Edwards, Meghan K; Rhodes, Ryan E; Loprinzi, Paul D
2017-09-01
Exercise may help to cope with hectic or demanding events after a stressful situation occurs. Limited research has evaluated whether exercise, prior to a stressor, helps to facilitate subsequent emotional regulation. This pilot study addresses this novel paradigm. We employed a randomized controlled trial evaluating the effects of acute exercise on emotional regulation. Participants were randomly assigned to stretch (control group, N = 10), walk (N = 9), or jog (N = 8) for 15-minutes, after which they were exposed to a film clip intended to elicit a negative emotional response. Participants' emotions were monitored before and during exercise, as well as after the film clip. Emotional responses were evaluated using the Exercise Induced Feeling Inventory and Affective Circumplex Scale. A group x time splitplot interaction effect was significant for anger (p = .046) and anxiousness (p = .038). Follow-up analyses showed that only the stretching group (p = .048) had a significantly increased anger score from baseline to post-film clip, suggesting a protective emotional effect from walking and jogging. Exercise was effective in regulating anger and anxiousness after a stressful event. These findings provide evidence for potential preventive effects of exercise in facilitating emotional regulation.
B7-H1 limits the entry of effector CD8(+) T cells to the memory pool by upregulating Bim.
Gibbons, Rachel M; Liu, Xin; Pulko, Vesna; Harrington, Susan M; Krco, Christopher J; Kwon, Eugene D; Dong, Haidong
2012-10-01
Protective T‑cell immunity against cancer and infections is dependent on the generation of a durable effector and memory T‑cell pool. Studies from cancer and chronic infections reveal that B7-H1 (PD-L1) engagement with its receptor PD-1 promotes apoptosis of effector T cells. It is not clear how B7-H1 regulates T‑cell apoptosis and the subsequent impact of B7-H1 on the generation of memory T cells. In immunized B7-H1-deficient mice, we detected an increased expansion of effector CD8(+) T cells and a delayed T‑cell contraction followed by the emergence of a protective CD8(+) T‑cell memory capable of completely rejecting tumor metastases in the lung. Intracellular staining revealed that antigen-primed CD8(+) T cells in B7-H1-deficient mice express lower levels of the pro-apoptotic molecule Bim. The engagement of activated CD8(+) T cells by a plate-bound B7-H1 fusion protein led to the upregulation of Bim and increased cell death. Assays based on blocking antibodies determined that both PD-1 and CD80 are involved in the B7-H1-mediated regulation of Bim in activated CD8(+) T cells. Our results suggest that B7-H1 may negatively regulate CD8(+) T‑cell memory by enhancing the depletion of effector CD8(+) T cells through the upregulation of Bim. Our findings may provide a new strategy for targeting B7-H1 signaling in effector CD8(+) T cells to achieve protective antitumor memory responses.
Xia, Jingwen; Jiang, Nianxin; Li, Yansong; Wei, Yong; Zhang, Xuan
2018-05-10
Myocardial infarction (MI) is a leading cause of disease with high morbidity and mortality worldwide. Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in heart disease pathogenesis. This study aimed to investigate the effect and the molecular basis of THRIL on hypoxia-injured H9C2 cells. THRIL, miR-99a and Brahma-related gene 1 (Brg1) expression in H9C2 cells were altered by transient transfections. The cells were subjected to hypoxia for 4 h, and then the levels of THRIL, miR-99a and Brg1 were investigated. Cell viability, migration and invasion, and apoptotic cells were respectively measured by trypan blue exclusion assay, transwell migration assay and flow cytometry assay. Dual luciferase reporter assay was conducted to verify the interaction between miR-99a and THRIL. Furthermore, levels of apoptosis-, PI3K/AKT and mTOR pathways-related factors were measured by western blotting. Hypoxia induced an increase of THRIL but a reduction of miR-99a and Brg1. THRIL inhibition significantly attenuated hypoxia-induced cell injuries, as increased cell viability, migration and invasion, and decreased cell apoptosis. THRIL negatively regulated miR-99a expression through sponging with miR-99a binding site, and miR-99a inhibition abolished the protective effects of THRIL knockdown against hypoxia-induced injury in H9C2 cells. Furthermore, miR-99a positively regulated the expression of Brg1. Brg1 inhibition promoted hypoxia-induced cell injuries, while Brg1 overexpression alleviated hypoxia-induced cell injuries. Moreover, Brg1 overexpression activated PI3K/AKT and mTOR pathways. This study demonstrates that THRIL inhibition represents a protective effect against hypoxia-induced injuries in H9C2 cells by up-regulating miR-99a expression.
40 CFR 62.10634 - Identification of plan-negative declarations.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of plan-negative declarations. 62.10634 Section 62.10634 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF STATE PLANS FOR DESIGNATED FACILITIES AND POLLUTANTS Tennessee Air Emissions from Existing...
40 CFR 62.10631 - Identification of plan-negative declarations.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of plan-negative declarations. 62.10631 Section 62.10631 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF STATE PLANS FOR DESIGNATED FACILITIES AND POLLUTANTS Tennessee Air Emissions from Existing...
Emotion regulation ability varies in relation to intrinsic functional brain architecture
Uchida, Mai; Biederman, Joseph; Gabrieli, John D. E.; Micco, Jamie; de Los Angeles, Carlo; Brown, Ariel; Kenworthy, Tara; Kagan, Elana
2015-01-01
This study investigated the neural basis of individual variation in emotion regulation, specifically the ability to reappraise negative stimuli so as to down-regulate negative affect. Brain functions in young adults were measured with functional Magnetic Resonance Imaging during three conditions: (i) attending to neutral pictures; (ii) attending to negative pictures and (iii) reappraising negative pictures. Resting-state functional connectivity was measured with amygdala and dorsolateral prefrontal cortical (DLPFC) seed regions frequently associated with emotion regulation. Participants reported more negative affect after attending to negative than neutral pictures, and less negative affect following reappraisal. Both attending to negative vs neutral pictures and reappraising vs attending to negative pictures yielded widespread activations that were significantly right-lateralized for attending to negative pictures and left-lateralized for reappraising negative pictures. Across participants, more successful reappraisal correlated with less trait anxiety and more positive daily emotion, greater activation in medial and lateral prefrontal regions, and lesser resting-state functional connectivity between (a) right amygdala and both medial prefrontal and posterior cingulate cortices, and (b) bilateral DLPFC and posterior visual cortices. The ability to regulate emotion, a source of resilience or of risk for distress, appears to vary in relation to differences in intrinsic functional brain architecture. PMID:25999363
Emotion regulation ability varies in relation to intrinsic functional brain architecture.
Uchida, Mai; Biederman, Joseph; Gabrieli, John D E; Micco, Jamie; de Los Angeles, Carlo; Brown, Ariel; Kenworthy, Tara; Kagan, Elana; Whitfield-Gabrieli, Susan
2015-12-01
This study investigated the neural basis of individual variation in emotion regulation, specifically the ability to reappraise negative stimuli so as to down-regulate negative affect. Brain functions in young adults were measured with functional Magnetic Resonance Imaging during three conditions: (i) attending to neutral pictures; (ii) attending to negative pictures and (iii) reappraising negative pictures. Resting-state functional connectivity was measured with amygdala and dorsolateral prefrontal cortical (DLPFC) seed regions frequently associated with emotion regulation. Participants reported more negative affect after attending to negative than neutral pictures, and less negative affect following reappraisal. Both attending to negative vs neutral pictures and reappraising vs attending to negative pictures yielded widespread activations that were significantly right-lateralized for attending to negative pictures and left-lateralized for reappraising negative pictures. Across participants, more successful reappraisal correlated with less trait anxiety and more positive daily emotion, greater activation in medial and lateral prefrontal regions, and lesser resting-state functional connectivity between (a) right amygdala and both medial prefrontal and posterior cingulate cortices, and (b) bilateral DLPFC and posterior visual cortices. The ability to regulate emotion, a source of resilience or of risk for distress, appears to vary in relation to differences in intrinsic functional brain architecture. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
U.S. ENVIRONMENTAL PROTECTION AGENCY'S REGULATION AND MANAGEMENT OF WATERBORNE VIRUSES
The U.S. Environmental Protection Agency (USEPA) manages waterborne viruses and other pathogens through the establishment of rules and regulations that are designed to ensure public health protection. The rules that currently regulate pathogens focus on the management of viruses...
40 CFR 191.25 - Compliance with other Federal regulations.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Compliance with other Federal regulations. 191.25 Section 191.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS ENVIRONMENTAL RADIATION PROTECTION STANDARDS FOR MANAGEMENT AND DISPOSAL OF...
40 CFR 191.25 - Compliance with other Federal regulations.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Compliance with other Federal regulations. 191.25 Section 191.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS ENVIRONMENTAL RADIATION PROTECTION STANDARDS FOR MANAGEMENT AND DISPOSAL OF...
40 CFR 191.25 - Compliance with other Federal regulations.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Compliance with other Federal regulations. 191.25 Section 191.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS ENVIRONMENTAL RADIATION PROTECTION STANDARDS FOR MANAGEMENT AND DISPOSAL OF...
40 CFR 191.25 - Compliance with other Federal regulations.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Compliance with other Federal regulations. 191.25 Section 191.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS ENVIRONMENTAL RADIATION PROTECTION STANDARDS FOR MANAGEMENT AND DISPOSAL OF...
40 CFR 191.25 - Compliance with other Federal regulations.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Compliance with other Federal regulations. 191.25 Section 191.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS ENVIRONMENTAL RADIATION PROTECTION STANDARDS FOR MANAGEMENT AND DISPOSAL OF...
Pathways from marine protected area design and management to ecological success
2015-01-01
Using an international dataset compiled from 121 sites in 87 marine protected areas (MPAs) globally (Edgar et al., 2014), I assessed how various configurations of design and management conditions affected MPA ecological performance, measured in terms of fish species richness and biomass. The set-theoretic approach used Boolean algebra to identify pathways that combined up to five ‘NEOLI’ (No-take, Enforced, Old, Large, Isolated) conditions and that were sufficient for achieving positive, and negative, ecological outcomes. Ecological isolation was overwhelming the most important condition affecting ecological outcomes but Old and Large were also conditions important for achieving high levels of biomass among large fishes (jacks, groupers, sharks). Solution coverage was uniformly low (<0.35) for all models of positive ecological performance suggesting the presence of numerous other conditions and pathways to ecological success that did not involve the NEOLI conditions. Solution coverage was higher (>0.50) for negative results (i.e., the absence of high biomass) among the large commercially-exploited fishes, implying asymmetries in how MPAs may rebuild populations on the one hand and, on the other, protect against further decline. The results revealed complex interactions involving MPA design, implementation, and management conditions that affect MPA ecological performance. In general terms, the presence of no-take regulations and effective enforcement were insufficient to ensure MPA effectiveness on their own. Given the central role of ecological isolation in securing ecological benefits from MPAs, site selection in the design phase appears critical for success. PMID:26644975
Xie, B; Li, D; London, S J; Palmer, P H; Johnshon, C A; Li, Y; Shih, J; Bergen, A W; Nishita, D; Swan, G E; Ahn, R; Conti, D V
2014-10-01
Monoamine oxidase A (MAOA) modulates metabolism of serotonin and dopamine metabolism, neurotransmitters involved in regulation of appetite and food intake. The gene coding for MAOA contains a 30-bp tandem repeat (uVNTR) polymorphism in its promoter region that has been previously identified to be associated with obesity with mixed findings in the literature. Our goals were to replicate the population effects of this functional polymorphism on obesity risk, and to further explore gender differences and interaction effects with negative stressors. Analyses were conducted with data on genotypes, measured weight and height, and self-reported behavioural characteristics among 1101 Chinese adolescents 11-15 years old living in Wuhan, China. Girls with the high-activity allele had significantly lower body mass index (BMI; β = -0.25 ± 0.98, P = 0.011) compared to those with the low activity allele. Experience of negative familial stressors (e.g., death or illness of family members, hit or scolded by parents and increased quarrelling with parents, parents argued frequently) significantly weakened this protective genetic effect on BMI (P for interaction = 0.043). Stratified analyses showed a significant protective genetic effect on BMI only within the stratum of low stress level (β = -0.44 ± 0.14, P = 0.002). No similar effect was observed among boys. Our findings confirm the genetic effects of MAOA uVNTR polymorphism on BMI in a Chinese adolescent population and suggest potential genetic interactions with negative familial stressors. © 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.
40 CFR 403.2 - Objectives of general pretreatment regulations.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 30 2013-07-01 2012-07-01 true Objectives of general pretreatment regulations. 403.2 Section 403.2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... POLLUTION § 403.2 Objectives of general pretreatment regulations. By establishing the responsibilities of...
40 CFR 52.1527 - Rules and regulations.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Rules and regulations. 52.1527 Section 52.1527 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New Hampshire § 52.1527 Rules and regulations...
40 CFR 52.1527 - Rules and regulations.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Rules and regulations. 52.1527 Section 52.1527 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New Hampshire § 52.1527 Rules and regulations...
40 CFR 52.1527 - Rules and regulations.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 40 Protection of Environment 4 2012-07-01 2012-07-01 false Rules and regulations. 52.1527 Section 52.1527 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New Hampshire § 52.1527 Rules and regulations...
40 CFR 52.1527 - Rules and regulations.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Rules and regulations. 52.1527 Section 52.1527 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New Hampshire § 52.1527 Rules and regulations...
40 CFR 52.1527 - Rules and regulations.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Rules and regulations. 52.1527 Section 52.1527 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New Hampshire § 52.1527 Rules and regulations...
[Behavior in the forced-swimming test and expression of BDNF and Bcl-xl genes in the rat brain].
Berezova, I V; Shishkina, G T; Kalinina, T S; Dygalo, N N
2011-01-01
A single exposure of rats to the forced-swimming stress decreased BDNF mRNA levels in the cortex and increased Bcl-xl gene expression in the hippocampus and amygdala 24 h after the stress. The animals demonstrated a depressive-like behavior and elevated blood corticosterone level. There was a significant negative correlation between BDNF mRNA level in the cortex and immobility time during swimming. Repeated exposure to swimming stress caused the elevation of the hippocampal BDNF mRNA level assessed 24 h after the second swimming session. The data suggest that stress-induced down-regulation of cortical BDNF gene expression and behavioral despair in the forced-swimming test may be interrelated. The increase in the BDNF and Bcl-xl mRNA levels may contribute to the mechanisms protecting the brain against negative effects of stress.
Kerret, Dorit; Menahem, Gila; Sagi, Rinat
2010-11-01
Focusing on the potential of information regulations, this article aims to contribute to ongoing efforts of policymakers to improve policy tools, in light of the increasing complexity of assessing the environmental impacts of new technologies and industrial corporations. Using the annual reports of corporations and performance data from the Ministry of Environmental Protection, the study analyzed the quality of responses to the amendments of Israel's Securities Regulations by major, publicly traded, polluting industrial corporations in Israel. The main theoretical claim of this paper is that within mandatory regulations there may be a large variability in the degree of specification of requirements. When considerable discretion is left to corporations, the result is a mixed mandatory-voluntary regulation regime. Our findings suggest that such variability impacts the implementation outcomes, as responses to environmental requirements depend on the level of discretion. Facilities increased their reported information, including the negative aspects, when specific mandatory prescriptions were stipulated. However, voluntary motivations did not result in the provision of information when corporations were allowed a high level of discretion. The authors recommend the delineation of exact stipulations of prescriptive requirements for the provision of comparative environmental information in order to obtain the environmental information deemed necessary.
Carrying guns in public: legal and public health implications.
Vernick, Jon S
2013-03-01
In District of Columbia v. Heller, the U.S. Supreme Court ruled that the Second Amendment protects an individual's right to own handguns in the home for protection, invalidating a Washington, D.C. law banning most handgun possession. The Heller decision, however, provided lower courts with little guidance regarding how to judge the constitutionality of gun laws other than handgun bans. Nevertheless, lower courts have upheld the vast majority of federal, state, and local gun laws challenged since Heller. One area in which some lower courts have disagreed has been the constitutionality of laws regulating the ability to carry firearms in public. This issue may be the next to be addressed by the Supreme Court under its evolving Second Amendment jurisprudence. Courts should carefully consider the negative public health and safety implications of gun carrying in public as they weigh the constitutionality of these laws. © 2013 American Society of Law, Medicine & Ethics, Inc.
Is motivation for marathon a protective factor or a risk factor of injury?
Chalabaev, A; Radel, R; Ben Mahmoud, I; Massiera, B; Deroche, T; d'Arripe-Longueville, F
2017-12-01
This research investigated whether and how self-determined motivation predicts perceived susceptibility to injury during competition (marathon). Two correlational studies including 378 (Study 1) and 339 (Study 2) marathon runners were conducted. Participants filled out a questionnaire the day before the race measuring self-determined motivation, perceived susceptibilities to marathon-related injury and to keep running through pain, and control variables. Study 1 showed that self-determined motivation was negatively related to perceived susceptibility to marathon-related injury. Study 2 replicated this finding and showed that this relationship was partially mediated by perceived susceptibility to keep running through pain during the race. Moreover, results indicated that the predictive role of self-determination was mostly driven by controlled forms of motivation, and more particularly external regulation. These results suggest that self-determined motivation for sport is a protective factor of injury. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Li, Xiaomin; Wang, Jianjun; Zhang, Chao; Lin, Chun; Zhang, Jianming; Zhang, Wei; Zhang, Wenjuan; Lu, Yanxia; Zheng, Lin; Li, Xuenong
2018-06-26
Circular RNAs (circRNAs) are significantly dysregulated in various cancer types. However, the roles and mechanisms of circRNAs in cancer remain largely unknown. In this study, we demonstrated that a novel circRNA (circITGA7) and its linear host gene ITGA7 are both significantly downregulated in colorectal cancer (CRC) tissues and cell lines. These decreased expression levels correlated with CRC progression. Functional assays demonstrated that ectopic circITGA7 expression suppressed the growth and metastasis of CRC cell in vitro and in vivo. Knockdown of circITGA7 or ITGA7 promoted the proliferation and migration of CRC cells in vitro and enhanced CRC growth in vivo. Mechanistically, we found that circITGA7 is a negative regulator of the Ras signalling pathway and ITGA7 is associated with cytokine-related signalling pathways through RNA-seq and KEGG enrichment analysis. In addition, circITGA7 binds to miR-370-3p to antagonize its suppression of NF1, which is a well-known negative regulator of the Ras pathway. Finally, circITGA7 upregulates the transcription of ITGA7 by suppressing RREB1 via the Ras pathway. In conclusion, our findings indicate a suppressor role of circITGA7 and ITGA7 in CRC and reveal that circITGA7 inhibits proliferation and metastasis of CRC cells by suppressing the Ras signalling pathway and promoting the transcription of ITGA7, suggesting that circITGA7 is a potential target for CRC treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Dvorak, Robert D; Pearson, Matthew R; Neighbors, Clayton; Martens, Matthew P; Stevenson, Brittany L; Kuvaas, Nicholas J
2016-06-01
Drinking remains a problem across college campuses. Changing this behavior requires interventions that can be easily and widely dispersed. Several theories place intentions as a proximal predictor of behavior change. The current study examines the effects of a Web-based Deviance Regulation Theory (DRT) intervention on (1) intentions to use alcohol protective behavior strategies (PBS) and (2) associations between these intentions and actual behavior. Participants (n = 76) completed a 6-week, Web-based study examining drinking behaviors. Participants were randomly assigned to receive a positive frame about individuals who use PBS or a negative frame about individuals who do not. They also reported normative perceptions of PBS use among college students. They subsequently logged onto a secure server each week to report on alcohol involvement, use of 3 types of PBS (Manner of Drinking, Stopping/Limiting, and Serious Harm Reduction), and intentions to use these PBS the following week. Consistent with DRT, negative frames resulted in higher PBS use intentions if individuals held high normative beliefs about PBS use. Positive frames resulted in higher Manner of Drinking PBS use intentions if individuals held low normative beliefs about PBS use, but only if individuals endorsed a high belief in the frame. In addition, there was a DRT consistent increase in intention-action associations, but only for Stopping/Limiting PBS. A brief Web-based DRT intervention was effective at increasing PBS intentions and increasing PBS intention-action associations. DRT may provide a mechanism to additively or synergistically improve other Web-based interventions for college drinking. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
40 CFR 52.2678 - Control strategy and regulations: Particulate matter.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy and regulations: Particulate matter. 52.2678 Section 52.2678 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....2678 Control strategy and regulations: Particulate matter. (a) The requirements of § 51.110(a) and...
40 CFR 52.2678 - Control strategy and regulations: Particulate matter.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy and regulations: Particulate matter. 52.2678 Section 52.2678 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....2678 Control strategy and regulations: Particulate matter. (a) The requirements of § 51.110(a) and...
40 CFR 52.2679 - Control strategy and regulations: Sulfur dioxide.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 5 2013-07-01 2013-07-01 false Control strategy and regulations: Sulfur dioxide. 52.2679 Section 52.2679 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....2679 Control strategy and regulations: Sulfur dioxide. (a) Approvals of the following rules are limited...
40 CFR 52.2679 - Control strategy and regulations: Sulfur dioxide.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy and regulations: Sulfur dioxide. 52.2679 Section 52.2679 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....2679 Control strategy and regulations: Sulfur dioxide. (a) Approvals of the following rules are limited...
40 CFR 52.2679 - Control strategy and regulations: Sulfur dioxide.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 40 Protection of Environment 5 2012-07-01 2012-07-01 false Control strategy and regulations: Sulfur dioxide. 52.2679 Section 52.2679 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....2679 Control strategy and regulations: Sulfur dioxide. (a) Approvals of the following rules are limited...
40 CFR 52.2679 - Control strategy and regulations: Sulfur dioxide.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy and regulations: Sulfur dioxide. 52.2679 Section 52.2679 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....2679 Control strategy and regulations: Sulfur dioxide. (a) Approvals of the following rules are limited...
40 CFR 52.2679 - Control strategy and regulations: Sulfur dioxide.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 5 2014-07-01 2014-07-01 false Control strategy and regulations: Sulfur dioxide. 52.2679 Section 52.2679 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....2679 Control strategy and regulations: Sulfur dioxide. (a) Approvals of the following rules are limited...
Davis, Tchiki S; Mauss, Iris B; Lumian, Daniel; Troy, Allison S; Shallcross, Amanda J; Zarolia, Paree; Ford, Brett Q; McRae, Kateri
2014-08-01
Intentionally hurting one's body (deliberate self-harm; DSH) is theorized to be associated with high negative emotional reactivity and poor emotion regulation ability. However, little research has assessed the relationship between these potential risk factors and DSH using laboratory measures. Therefore, we conducted 2 studies using laboratory measures of negative emotional reactivity and emotion regulation ability. Study 1 assessed self-reported negative emotions during a sad film clip (reactivity) and during a sad film clip for which participants were instructed to use reappraisal (regulation). Those with a history of DSH were compared with 2 control groups without a history of DSH matched on key demographics: 1 healthy group low in depression and anxiety symptoms and 1 group matched to the DSH group on depression and anxiety symptoms. Study 2 extended Study 1 by assessing neural responding to negative images (reactivity) and negative images for which participants were instructed to use reappraisal (regulation). Those with a history of DSH were compared with a control group matched to the DSH group on demographics, depression, and anxiety symptoms. Compared with control groups, participants with a history of DSH did not exhibit greater negative emotional reactivity but did exhibit lower ability to regulate emotion with reappraisal (greater self-reported negative emotions in Study 1 and greater amygdala activation in Study 2 during regulation). These results suggest that poor emotion regulation ability, but not necessarily greater negative emotional reactivity, is a correlate of and may be a risk factor for DSH, even when controlling for mood disorder symptoms. (c) 2014 APA, all rights reserved.
Davis, Tchiki S.; Mauss, Iris B.; Lumian, Daniel; Troy, Allison S.; Shallcross, Amanda J.; Zarolia, Paree; Ford, Brett Q.; McRae, Kateri
2014-01-01
Intentionally hurting one’s own body (deliberate self-harm; DSH) is theorized to be associated with high negative emotional reactivity and poor emotion regulation ability. However, little research has assessed the relationship between these potential risk factors and DSH using laboratory measures. Therefore, we conducted two studies using laboratory measures of negative emotional reactivity and emotion regulation ability. Study 1 assessed self-reported negative emotions during a sad film clip (Reactivity) and during a sad film clip for which participants were instructed to use reappraisal (Regulation). Those with a history of DSH were compared to two control groups without a history of DSH matched on key demographics: one healthy group low in depression and anxiety symptoms and one group matched to the DSH group on depression and anxiety symptoms. Study 2 extended Study 1 by assessing neural responding to negative images (Reactivity) and negative images for which participants were instructed to use reappraisal (Regulation). Those with a history of DSH were compared to a control group matched to the DSH group on demographics, depression, and anxiety symptoms. Compared to control groups, participants with a history of DSH did not exhibit greater negative emotional reactivity but did exhibit lower ability to regulate emotion with reappraisal (greater self-reported negative emotions in Study 1 and greater amygdala activation in Study 2 during regulation). These results suggest that poor emotion regulation ability, but not necessarily greater negative emotional reactivity, is a correlate of and may be a risk factor for DSH, even when controlling for mood disorder symptoms. PMID:24865373
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…
Ghorbani, Fatemeh; Khosravani, Vahid; Sharifi Bastan, Farangis; Jamaati Ardakani, Razieh
2017-06-01
The aim of this study was to evaluate the potential contributing factors such as alexithymia, emotion regulation and difficulties in emotion regulation, positive/negative affects and clinical factors including severity of alcohol dependence and depression connected to high suicidality in alcohol-dependent outpatients. 205 alcohol-dependent outpatients and 100 normal controls completed the demographic questionnaire, the Persian version of the Toronto Alexithymia Scale (FTAS-20), the Difficulties in Emotion Regulation Scale (DERS), the Emotion Regulation Questionnaire (ERQ), the Positive/Negative Affect Scales, the Alcohol Use Disorders Identification Test (AUDIT), and the Beck Depression Inventory-II (BDI-II). The suicidal risk was assessed using the Scale for Suicide Ideation (SSI) and history taking. Alcohol-dependent outpatients showed higher means in alexithymia, difficulties in emotion regulation, suppression subscale, negative affect, and suicide ideation than normal controls. Logistic regression analysis revealed that negative affect, duration of alcohol use, externally-oriented thinking, and severity of alcohol dependence explained lifetime suicide attempts. Depression, impulsivity, severity of alcohol dependence, reappraisal (reversely), externally-oriented thinking, difficulties engaging in goal-directed behaviors, and negative affect significantly predicted the suicidal risk. The findings may constitute useful evidence of the relevancies of alexithymia, emotion regulation, emotion regulation difficulties, and affects to suicidality in alcoholic patients. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.
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…
Farrell, Anne M.; Goh, Joshua O. S.; White, Brian J.
2018-01-01
Emotional and economic incentives often conflict in decision environments. To make economically desirable decisions then, deliberative neural processes must be engaged to regulate automatic emotional reactions. In this functional magnetic resonance imaging (fMRI) study, we evaluated how fixed wage (FW) incentives and performance-based (PB) financial incentives, in which pay is proportional to outcome, differentially regulate positive and negative emotional reactions to hypothetical colleagues that conflicted with the economics of available alternatives. Neural activity from FW to PB incentive contexts decreased for positive emotional stimuli but increased for negative stimuli in middle temporal, insula, and medial prefrontal regions. In addition, PB incentives further induced greater responses to negative than positive emotional decisions in the frontal and anterior cingulate regions involved in emotion regulation. Greater response to positive than negative emotional features in these regions also correlated with lower frequencies of economically desirable choices. Our findings suggest that whereas positive emotion regulation involves a reduction of responses in valence representation regions, negative emotion regulation additionally engages brain regions for deliberative processing and signaling of incongruous events. PMID:29487519
Farrell, Anne M; Goh, Joshua O S; White, Brian J
2018-01-01
Emotional and economic incentives often conflict in decision environments. To make economically desirable decisions then, deliberative neural processes must be engaged to regulate automatic emotional reactions. In this functional magnetic resonance imaging (fMRI) study, we evaluated how fixed wage (FW) incentives and performance-based (PB) financial incentives, in which pay is proportional to outcome, differentially regulate positive and negative emotional reactions to hypothetical colleagues that conflicted with the economics of available alternatives. Neural activity from FW to PB incentive contexts decreased for positive emotional stimuli but increased for negative stimuli in middle temporal, insula, and medial prefrontal regions. In addition, PB incentives further induced greater responses to negative than positive emotional decisions in the frontal and anterior cingulate regions involved in emotion regulation. Greater response to positive than negative emotional features in these regions also correlated with lower frequencies of economically desirable choices. Our findings suggest that whereas positive emotion regulation involves a reduction of responses in valence representation regions, negative emotion regulation additionally engages brain regions for deliberative processing and signaling of incongruous events.
Hurrell, Katherine E; Hudson, Jennifer L; Schniering, Carolyn A
2015-01-01
Research has demonstrated that parental reactions to children's emotions play a significant role in the development of children's emotion regulation (ER) and adjustment. This study compared parent reactions to children's negative emotions between families of anxious and non-anxious children (aged 7-12) and examined associations between parent reactions and children's ER. Results indicated that children diagnosed with an anxiety disorder had significantly greater difficulty regulating a range of negative emotions and were regarded as more emotionally negative and labile by their parents. Results also suggested that mothers of anxious children espoused less supportive parental emotional styles when responding to their children's negative emotions. Supportive and non-supportive parenting reactions to children's negative emotions related to children's emotion regulation skills, with father's non-supportive parenting showing a unique relationship to children's negativity/lability. Copyright © 2015 Elsevier Ltd. All rights reserved.
40 CFR 60.4315 - What pollutants are regulated by this subpart?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 6 2010-07-01 2010-07-01 false What pollutants are regulated by this subpart? 60.4315 Section 60.4315 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... pollutants regulated by this subpart are nitrogen oxide (NOX) and sulfur dioxide (SO2). ...
40 CFR 52.271 - Malfunction, startup, and shutdown regulations.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Malfunction, startup, and shutdown regulations. 52.271 Section 52.271 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.271 Malfunction, startup, and shutdown regulations. (a)...
40 CFR 52.271 - Malfunction, startup, and shutdown regulations.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Malfunction, startup, and shutdown regulations. 52.271 Section 52.271 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.271 Malfunction, startup, and shutdown regulations. (a)...
40 CFR 52.271 - Malfunction, startup, and shutdown regulations.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Malfunction, startup, and shutdown regulations. 52.271 Section 52.271 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.271 Malfunction, startup, and shutdown regulations. (a)...
40 CFR 52.271 - Malfunction, startup, and shutdown regulations.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Malfunction, startup, and shutdown regulations. 52.271 Section 52.271 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.271 Malfunction, startup, and shutdown regulations. (a)...
40 CFR 52.271 - Malfunction, startup, and shutdown regulations.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Malfunction, startup, and shutdown regulations. 52.271 Section 52.271 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.271 Malfunction, startup, and shutdown regulations. (a)...
40 CFR 52.1627 - Control strategy and regulations: Carbon monoxide.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy and regulations: Carbon monoxide. 52.1627 Section 52.1627 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New Mexico § 52.1627 Control strategy and regulations:...
40 CFR 52.1627 - Control strategy and regulations: Carbon monoxide.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy and regulations: Carbon monoxide. 52.1627 Section 52.1627 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New Mexico § 52.1627 Control strategy and regulations:...
40 CFR 52.131 - Control Strategy and regulations: Fine Particle Matter.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control Strategy and regulations: Fine Particle Matter. 52.131 Section 52.131 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Strategy and regulations: Fine Particle Matter. (a) Determination of Attainment: Effective February 6, 2013...
40 CFR 52.247 - Control Strategy and regulations: Fine Particle Matter.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control Strategy and regulations: Fine Particle Matter. 52.247 Section 52.247 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Strategy and regulations: Fine Particle Matter. (a) Determination of Attainment: Effective February 8, 2013...
40 CFR 52.247 - Control Strategy and regulations: Fine Particle Matter.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control Strategy and regulations: Fine Particle Matter. 52.247 Section 52.247 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Strategy and regulations: Fine Particle Matter. (a) Determination of Attainment: Effective February 8, 2013...
40 CFR 52.131 - Control Strategy and regulations: Fine Particle Matter.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control Strategy and regulations: Fine Particle Matter. 52.131 Section 52.131 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Strategy and regulations: Fine Particle Matter. (a) Determination of Attainment: Effective February 6, 2013...
Peters, Luisa; Franke, Laura; Tkachenko, Daria; Schiffer, Mario; Zimmermann, Tanja
2018-05-01
Nonadherence to immunosuppressive medication increases the risk of graft failure. Maladaptive emotion regulation strategies (ERS) seem to be a risk factor for nonadherence, whereas for patients in relationships spousal support appears as a protective resource. Emotional arousal, objectively measured by the fundamental frequency (f 0 ) during spousal supportive communication is associated with supportive behavior. This study examined the relationship between beliefs about immunosuppressive medication, quality of life, ERS, emotions and emotional arousal, assessed during social support interactions of both spouses of N=50 couples after kidney transplantation. Maladaptive ERS of the transplant recipient were associated with lower mental quality of life of the partner, marginally higher own negative affect and lower beliefs about medication. Maladaptive ERS of the partner showed negative correlations with own mental quality of life. Regarding f 0 , gender differences were found. Higher f 0 of the male transplant recipient were associated with more maladaptive ERS of the female partner. Marginally significate correlations were found with lower own beliefs about medication. Higher f 0 of the wife of the male transplant recipient showed correlations with lower own positive affect, more negative affect of the male patient and lower beliefs about medication. Higher f 0 of female transplant recipients were associated with lower own maladaptive ERS and lower maladaptive ERS of the husband. The findings support the relevance of early interventions focusing on identifying and modifying maladaptive ERS for both the patient and partner. © Georg Thieme Verlag KG Stuttgart · New York.
Zeigler-Hill, Virgil; Madson, Michael B; Ricedorf, Amy
2012-01-01
Previous research has shown that protective behavioral strategies tend to be associated with lower levels of alcohol consumption and fewer negative alcohol-related consequences. The purpose of the present study was to examine whether self-esteem would moderate the association between protective behavioral strategies and alcohol-related outcomes. Participants were undergraduates (94 men and 363 women) between the ages of 18-25 who reported that they had consumed alcohol within the past 30 days. Results showed that greater use of protective behavioral strategies was associated with lower rates of alcohol consumption, less harmful drinking patterns, and fewer negative consequences for everyone except men with low self-esteem. The implications of these findings for understanding the link between protective behavioral strategies and alcohol-related outcomes are discussed.
ERIC Educational Resources Information Center
Moorer, Kayla D.; Madson, Michael B.; Mohn, Richard S.; Nicholson, Bonnie C.
2013-01-01
Alcohol protective behavioral strategies (PBS) limit overall negative consequences; however, less is known about the relationship between PBS and negative sex-related consequences. The purpose of the current study was to examine the moderating effects of 2 distinct types of PBS--controlled consumption strategies and serious harm reduction…
Correlative Gene Expression to Protective Seroconversion in Rift Valley Fever Vaccinates.
Laughlin, Richard C; Drake, Kenneth L; Morrill, John C; Adams, L Garry
2016-01-01
Rift Valley fever Virus (RVFV), a negative-stranded RNA virus, is the etiological agent of the vector-borne zoonotic disease, Rift Valley fever (RVF). In both humans and livestock, protective immunity can be achieved through vaccination. Earlier and more recent vaccine trials in cattle and sheep demonstrated a strong neutralizing antibody and total IgG response induced by the RVF vaccine, authentic recombinant MP-12 (arMP-12). From previous work, protective immunity in sheep and cattle vaccinates normally occurs from 7 to 21 days after inoculation with arMP-12. While the serology and protective response induced by arMP-12 has been studied, little attention has been paid to the underlying molecular and genetic events occurring prior to the serologic immune response. To address this, we isolated RNA from whole blood of vaccinated calves over a time course of 21 days before and after vaccination with arMP-12. The time course RNAs were sequenced by RNASeq and bioinformatically analyzed. Our results revealed time-dependent activation or repression of numerous gene ontologies and pathways related to the vaccine induced immune response and its regulation. Additional bioinformatic analyses identified a correlative relationship between specific host immune response genes and protective immunity prior to the detection of protective serum neutralizing antibody responses. These results contribute an important proof of concept for identifying molecular and genetic components underlying the immune response to RVF vaccination and protection prior to serologic detection.
Situation Selection and Modification for Emotion Regulation in Younger and Older Adults.
Livingstone, Kimberly M; Isaacowitz, Derek M
2015-11-01
This research investigated age differences in use and effectiveness of situation selection and situation modification for emotion regulation. Socioemotional selectivity theory suggests stronger emotional well-being goals in older age; emotion regulation may support this goal. Younger and older adults assigned to an emotion regulation or "just view" condition first freely chose to engage with negative, neutral, or positive material (situation selection), then chose to view or skip negative and positive material (situation modification), rating affect after each experience. In both tasks, older adults in both goal conditions demonstrated pro-hedonic emotion regulation, spending less time with negative material compared to younger adults. Younger adults in the regulate condition also engaged in pro-hedonic situation selection, but not modification. Whereas situation selection was related to affect, modification of negative material was not. This research supports more frequent pro-hedonic motivation in older age, as well as age differences in use of early-stage emotion regulation.
Mckenney, D; Pouliot, K; Wang, Y; Murthy, V; Ulrich, M; Döring, G; Lee, J C; Goldmann, D A; Pier, G B
2000-09-29
Staphylococcus aureus and S. epidermidis are among the most common causes of nosocomial infection, and S. aureus is also of major concern to human health due to its occurrence in community-acquired infections. These staphylococcal species are also major pathogens for domesticated animals. We have previously identified poly-N-succinyl beta-1-6 glucosamine (PNSG) as the chemical form of the S. epidermidis capsular polysaccharide/adhesin (PS/A) which mediates adherence of coagulase-negative staphylococci (CoNS) to biomaterials, serves as the capsule for strains of CoNS that express PS/A, and is a target for protective antibodies. We have recently found that PNSG is made by S. aureus as well, where it is an environmentally regulated, in vivo-expressed surface polysaccharide and similarly serves as a target for protective immunity. Only a minority of fresh human clinical isolates of S. aureus elaborate PNSG in vitro but most could be induced to do so under specific in vitro growth conditions. However, by immunofluorescence microscopy, S. aureus cells in infected human sputa and lung elaborated PNSG. The ica genes, previously shown to encode proteins in CoNS that synthesize PNSG, were found by PCR in all S. aureus strains examined, and immunogenic and protective PNSG could be isolated from S. aureus. Active and passive immunization of mice with PNSG protected them against metastatic kidney infections after intravenous inoculation with eight phenotypically PNSG-negative S. aureus. Isolates recovered from kidneys expressed PNSG, but expression was lost with in vitro culture. Strong antibody responses to PNSG were elicited in S. aureus infected mice, and a PNSG-capsule was observed by electron microscopy on isolates directly plated from infected kidneys. PNSG represents a previously unidentified surface polysaccharide of S. aureus that is elaborated during human and animal infection and is a prominent target for protective antibodies.
Kwon, Hayeong; Jang, Donghwan; Choi, Moonjeong; Lee, Jaewoong; Jeong, Kyuho; Pak, Yunbae
2018-06-01
Insulin resistance, defined as attenuated sensitivity responding to insulin, impairs insulin action. Direct causes and molecular mechanisms of insulin resistance have thus far remained elusive. Here we show that alternative translation initiation (ATI) of Caveolin-2 (Cav-2) regulates insulin sensitivity. Cav-2β isoform yielded by ATI desensitizes insulin receptor (IR) via dephosphorylation by protein-tyrosine phosphatase 1B (PTP1B), and subsequent endocytosis and lysosomal degradation of IR, causing insulin resistance. Blockage of Cav-2 ATI protects against insulin resistance by preventing Cav-2β-PTP1B-directed IR desensitization, thereby normalizing insulin sensitivity and glucose uptake. Our findings show that Cav-2β is a negative regulator of IR signaling, and identify a mechanism causing insulin resistance through control of insulin sensitivity via Cav-2 ATI. Copyright © 2018 Elsevier B.V. All rights reserved.
Martins, Bruna; Sheppes, Gal; Gross, James J; Mather, Mara
2018-04-16
Previous research demonstrates that younger and older adults prefer distraction over engagement (reappraisal) when regulating high-intensity negative emotion. Older adults also demonstrate a greater bias for positive over negative information in attention and memory compared with younger adults. In this study, we investigated whether emotion regulation choice preferences may differ as a function of stimulus valence with age. The effect of stimulus intensity on negative and positive emotion regulation strategy preferences was investigated in younger and older men. Participants indicated whether they favored distraction or reappraisal to attenuate emotional reactions to negative and positive images that varied in intensity. Men in both age-groups preferred distraction over reappraisal when regulating high-intensity emotion. As no age-related strategic differences were found in negative emotion regulation preferences, older men chose to distract less from high-intensity positive images than did younger men. Older men demonstrated greater engagement with highly positive emotional contexts than did younger men. Thus, age differences in emotion regulation goals when faced with intense emotional stimuli depend on the valence of the emotional stimuli.
MBSR vs aerobic exercise in social anxiety: fMRI of emotion regulation of negative self-beliefs
Ziv, Michal; Jazaieri, Hooria; Hahn, Kevin; Gross, James J.
2013-01-01
Mindfulness-based stress reduction (MBSR) is thought to reduce emotional reactivity and enhance emotion regulation in patients with social anxiety disorder (SAD). The goal of this study was to examine the neural correlates of deploying attention to regulate responses to negative self-beliefs using functional magnetic resonance imaging. Participants were 56 patients with generalized SAD in a randomized controlled trial who were assigned to MBSR or a comparison aerobic exercise (AE) stress reduction program. Compared to AE, MBSR yielded greater (i) reductions in negative emotion when implementing regulation and (ii) increases in attention-related parietal cortical regions. Meditation practice was associated with decreases in negative emotion and social anxiety symptom severity, and increases in attention-related parietal cortex neural responses when implementing attention regulation of negative self-beliefs. Changes in attention regulation during MBSR may be an important psychological factor that helps to explain how mindfulness meditation training benefits patients with anxiety disorders. PMID:22586252
Code of Federal Regulations, 2010 CFR
2010-07-01
... Areas Thirteenth Coast Guard District § 165.1313 Security zone regulations, tank ship protection, Puget... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Security zone regulations, tank ship protection, Puget Sound and adjacent waters, Washington 165.1313 Section 165.1313 Navigation and...
van Duijvenvoorde, Anna C. K.; Bakermans-Kranenburg, Marian J.; Crone, Eveline A.
2016-01-01
Abstract Negative social feedback often generates aggressive feelings and behavior. Prior studies have investigated the neural basis of negative social feedback, but the underlying neural mechanisms of aggression regulation following negative social feedback remain largely undiscovered. In the current study, participants viewed pictures of peers with feedback (positive, neutral or negative) to the participant’s personal profile. Next, participants responded to the peer feedback by pressing a button, thereby producing a loud noise toward the peer, as an index of aggression. Behavioral analyses showed that negative feedback led to more aggression (longer noise blasts). Conjunction neuroimaging analyses revealed that both positive and negative feedback were associated with increased activity in the medial prefrontal cortex (PFC) and bilateral insula. In addition, more activation in the right dorsal lateral PFC (dlPFC) during negative feedback vs neutral feedback was associated with shorter noise blasts in response to negative social feedback, suggesting a potential role of dlPFC in aggression regulation, or top-down control over affective impulsive actions. This study demonstrates a role of the dlPFC in the regulation of aggressive social behavior. PMID:26755768
Knecht, Hans; Mai, Sabine
2017-06-27
Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is expressed in germinal-center-derived, mononuclear Hodgkin (H) and multinuclear, diagnostic Reed-Sternberg (RS) cells in classical EBV-positive Hodgkin's lymphoma (cHL). LMP1 expression in EBV-negative H-cell lines results in a significantly increased number of RS cells. In a conditional, germinal-center-derived B-cell in vitro system, LMP1 reversibly down-regulates the shelterin proteins, telomeric repeat binding factor (TRF)1, TRF2, and protection of telomeres (POT)1. This down-regulation is associated with progressive 3D shelterin disruption, resulting in telomere dysfunction, progression of complex chromosomal rearrangements, and multinuclearity. TRF2 appears to be the key player. Thus, we hypothesize that the 3D interaction of telomeres and TRF2 is disrupted in H cells, and directly associated with the formation of H and RS cells. Using quantitative 3D co-immuno-TRF2-telomere fluorescent in situ hybridization (3D TRF2/Telo-Q-FISH) applied to monolayers of primary H and RS cells, we demonstrate TRF2-telomere dysfunction in EBV-positive cHL. However, in EBV-negative cHL a second molecular mechanism characterized by massive up-regulation of TRF2, but attrition of telomere signals, is also identified. These facts point towards a shelterin-related pathogenesis of cHL, where two molecularly disparate mechanisms converge at the level of 3D Telomere-TRF2 interactions, leading to the formation of RS cells.
Blanc, Mathieu; Hsieh, Wei Yuan; Robertson, Kevin A.; Watterson, Steven; Shui, Guanghou; Lacaze, Paul; Khondoker, Mizanur; Dickinson, Paul; Sing, Garwin; Rodríguez-Martín, Sara; Phelan, Peter; Forster, Thorsten; Strobl, Birgit; Müller, Matthias; Riemersma, Rudolph; Osborne, Timothy; Wenk, Markus R.; Angulo, Ana; Ghazal, Peter
2011-01-01
Little is known about the protective role of inflammatory processes in modulating lipid metabolism in infection. Here we report an intimate link between the innate immune response to infection and regulation of the sterol metabolic network characterized by down-regulation of sterol biosynthesis by an interferon regulatory loop mechanism. In time-series experiments profiling genome-wide lipid-associated gene expression of macrophages, we show a selective and coordinated negative regulation of the complete sterol pathway upon viral infection or cytokine treatment with IFNγ or β but not TNF, IL1β, or IL6. Quantitative analysis at the protein level of selected sterol metabolic enzymes upon infection shows a similar level of suppression. Experimental testing of sterol metabolite levels using lipidomic-based measurements shows a reduction in metabolic output. On the basis of pharmacologic and RNAi inhibition of the sterol pathway we show augmented protection against viral infection, and in combination with metabolite rescue experiments, we identify the requirement of the mevalonate-isoprenoid branch of the sterol metabolic network in the protective response upon statin or IFNβ treatment. Conditioned media experiments from infected cells support an involvement of secreted type 1 interferon(s) to be sufficient for reducing the sterol pathway upon infection. Moreover, we show that infection of primary macrophages containing a genetic knockout of the major type I interferon, IFNβ, leads to only a partial suppression of the sterol pathway, while genetic knockout of the receptor for all type I interferon family members, ifnar1, or associated signaling component, tyk2, completely abolishes the reduction of the sterol biosynthetic activity upon infection. Levels of the proteolytically cleaved nuclear forms of SREBP2, a key transcriptional regulator of sterol biosynthesis, are reduced upon infection and IFNβ treatment at both the protein and de novo transcription level. The reduction in srebf2 gene transcription upon infection and IFN treatment is also found to be strictly dependent on ifnar1. Altogether these results show that type 1 IFN signaling is both necessary and sufficient for reducing the sterol metabolic network activity upon infection, thereby linking the regulation of the sterol pathway with interferon anti-viral defense responses. These findings bring a new link between sterol metabolism and interferon antiviral response and support the idea of using host metabolic modifiers of innate immunity as a potential antiviral strategy. PMID:21408089
Shi, Peng; Qu, Hongdang; Nian, Di; Chen, Yuhua; Liu, Xiaolin; Li, Qiang; Li, Qianqian; Wang, Chun; Ye, Ming; Ma, Bo
2018-06-13
Guillain-Barré syndrome (GBS) is a rare, autoimmune-mediated disease. The use of Bifidobacterium is reportedly effective in alleviating GBS since they act by regulating T helper (Th) cells. In this study, we explored the differentiation of T helper cell subsets in patients with GBS. We also evaluated the effect of GBS on Bifidobacterium levels in patients and the likely protective influence of this bacterium in alleviating the disease in an animal model. We used flow cytometry, and real-time polymerase chain reaction (PCR) to determine the T cell subsets differentiation among 30 GBS patients and 20 healthy controls (HC). The concentration of Bifidobacterium was assayed by real-time PCR. Experimental autoimmune neuritis (EAN) animal model was established to support the protective role of Bifidobacterium in GBS. The expression of Th cells, Th2 and Th17 in the patients was significantly higher than that in the HC, while Treg cells decreased substantially. Moreover, the levels of Bifidobacterium in the GBS patients were considerably lower than those in the HC, the concentration of Bifidobacterium correlating with Th2 and Th17 subsets negatively. Treatment with Bifidobacterium significantly reduced the levels of Th2 and Th17 and promoted the levels of Treg cells. We concluded from this study that Bifidobacterium alleviated GBS by regulating Th cells, although in-depth studies might be required to fully understand the mechanism of action. Copyright © 2018. Published by Elsevier B.V.
Ekas, Naomi V.; Braungart-Rieker, Julia M.; Lickenbrock, Diane M.; Zentall, Shannon R.; Maxwell, Scott M.
2010-01-01
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 mixed-effects models were conducted to determine the degree to which behavioral strategy use predicts subsequent negative affect and negative affect predicts subsequent strategy use. Results with mother-toddler and father-toddler dyads indicated that parent-focused strategies with an unresponsive parent were followed by increases in negative affect, whereas toy-focused strategies were followed by decreases in negative affect. Results also indicated that toddler negative affect serves to regulate behavioral strategy use within both parent contexts. PMID:21552335
The on/off switches of the mitochondrial uncoupling proteins
Azzu, Vian; Brand, Martin D.
2013-01-01
Mitochondrial uncoupling proteins disengage substrate oxidation from ADP phosphorylation by dissipating the proton electrochemical gradient that is required for ATP synthesis. In doing this, the archetypal uncoupling protein, UCP1, mediates adaptive thermogenesis. By contrast, its paralogues UCP2 and UCP3 are not thought to mediate whole body thermogenesis in mammals. Instead, they have been implicated in a variety of physiological and pathological processes, including protection from oxidative stress, negative regulation of glucose sensing systems and the adaptation of fatty acid oxidation capacity to starving. Although much work has been devoted to how these proteins are activated, little is known of the mechanisms that reverse this activation. PMID:20006514
Prospects and problems of direct-to-public genetic tests.
Tracy, Erin E
2008-09-01
Direct-to-consumer advertising of genetic tests is prevalent, poorly regulated and fraught with potential negative public-health ramifications. While some genetic tests are available through means that safeguard patient understanding of the implications of having genetic tests performed, others are available to anyone who has a credit card, without any individualized counseling, assessment of whether such tests are indicated, or interpretation of test results. While the US FDA, the Centers for Medicare and Medicaid Services and the Federal Trade Commission all have a regulatory role, most experts agree that the industry is not adequately being reigned in to best protect the public it serves.
Pecora, Giulia; Sette, Stefania; Baumgartner, Emma; Laghi, Fiorenzo; Spinrad, Tracy L
2015-08-28
The purpose of this study was to examine the moderating role of internalising negative emotionality (i.e., anxious, concerned, and embarrassed displays) in the association between children's self-regulation and social adjustment. Seventy-four Italian children (44 girls, 30 boys; M age = 35.05 months, SD = 3.57) were assessed using two self-regulation tasks. Internalising negative emotionality was assessed through observations of children's emotion expressions during the tasks. Teachers evaluated children's social competence and internalising and externalising problems. Results demonstrated that among children who exhibited internalising negative emotionality, self-regulation was positively associated with social competence and negatively related to externalising problems. Our results suggest that self-regulation may play a crucial role for social adjustment when children show emotions such as anxiety and embarrassment during challenging situations.
The temporal deployment of emotion regulation strategies during negative emotional episodes.
Kalokerinos, Elise K; Résibois, Maxime; Verduyn, Philippe; Kuppens, Peter
2017-04-01
Time is given a central place in theoretical models of emotion regulation (Gross, 1998, 2015), but key questions regarding the role of time remain unanswered. We investigated 2 such unanswered questions. First, we explored when different emotion regulation strategies were used within the course of an emotional episode in daily life. Second, we investigated the association between the temporal deployment of strategies and negative emotional experience. We conducted a daily diary study in which participants (N = 74) drew an intensity profile depicting the temporal unfolding of their negative emotional experience across daily events (N = 480), and mapped their usage of emotion regulation strategies onto this intensity profile. Strategies varied in their temporal deployment, with suppression and rumination occurring more at the beginning of the episode, and reappraisal and distraction occurring more toward the end of the episode. Strategies also varied in their association with negative emotion: rumination was positively associated with negative emotion, and reappraisal and distraction were negatively associated with negative emotion. Finally, both rumination and reappraisal interacted with time to predict negative emotional experience. Rumination was more strongly positively associated with negative emotions at the end of the episode than the beginning, but reappraisal was more strongly negatively associated with negative emotion at the beginning of the episode than the end. These findings highlight the importance of accounting for timing in the study of emotion regulation, as well as the necessity of studying these temporal processes in daily life. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Fitzgerald, Jacklynn M; Phan, K Luan; Kennedy, Amy E; Shankman, Stewart A; Langenecker, Scott A; Klumpp, Heide
2017-08-15
Emotion dysregulation is prominent in generalized anxiety disorder (GAD), characterized clinically by exaggerated reactivity to negative stimuli and difficulty in down-regulating this response. Although limited research implicates frontolimbic disturbances in GAD, whether neural aberrations occur during emotional reactivity, regulation, or both is not well understood. During functional magnetic resonance imaging (fMRI), 30 individuals with GAD and 30 healthy controls (HC) completed a well-validated explicit emotion regulation task designed to measure emotional reactivity and regulation of reactivity. During the task, participants viewed negative images ('Look-Negative' condition) and, on some trials, used a cognitive strategy to reduce negative affective response ('Reappraise' condition). Results from an Analysis of Variance corrected for whole brain multiple comparisons showed a significant group x condition interaction in the left amygdala and left inferior frontal gyrus (IFG). Results from post-hoc analyses showed that the GAD group engaged these regions to a greater extent than HCs during Look-Negative but not Reappraise. Behaviorally, the GAD group reported feeling more negative than the HC group in each condition, although both groups reported reduced negative affect following regulation. As comorbidity was permitted, the presence of concurrent disorders, like other anxiety disorders and depression, detracts our ability to classify neural engagement particular to GAD alone. Individuals with GAD exhibited over-engagement of amygdala and frontal regions during the viewing of negative images, compared to HCs. Together, these aberrations may indicate that deficits in emotional reactivity rather than regulation contribute to emotion dysregulation in those with GAD. Copyright © 2017. Published by Elsevier B.V.
ERIC Educational Resources Information Center
Shin, Junseob
2011-01-01
This study investigated the prevalence of client violence toward child protection workers and its negative impacts on the work attitudes of those workers compared with community service workers in South Korea. This study is based on the assumption that child protection workers are more vulnerable to violence than are community service workers…
Anyan, Frederick; Worsley, Lyn; Hjemdal, Odin
2017-10-01
Resilience has provided a useful framework that elucidates the effects of protective factors to overcome psychological adversities but studies that address the potential contingencies of resilience to protect against direct and indirect negative effects are lacking. These obvious gaps have also resulted in oversimplification of complex processes that can be clarified by moderated mediation associations. This study examines a conditional process modelling of the protective effects of resilience against indirect effects. Two separate samples were recruited in a cross-sectional survey from Australia and Norway to complete the Patient Health Questionnaire -9, Generalized Anxiety Disorder, Stressful Negative Life Events Questionnaire and the Resilience Scale for Adults. The final sample sizes were 206 (females=114; males=91; other=1) and 210 (females=155; males=55) for Australia and Norway respectively. Moderated mediation analyses were conducted across the samples. Anxiety symptoms mediated the relationship between exposure to stressful negative life events and depressive symptoms in both samples. Conditional indirect effects of exposure to stressful negative life events on depressive symptoms mediated by anxiety symptoms showed that high subgroup of resilience was associated with less effect of exposure to stressful negative life events through anxiety symptoms on depressive symptoms than the low subgroup of resilience. As a cross-sectional survey, the present study does not answer questions about causal processes despite the use of a conditional process modelling. These findings support that, resilience protective resources can protect against both direct and indirect - through other channels - psychological adversities. Copyright © 2017 Elsevier B.V. All rights reserved.
Prostaglandin E2 regulates B cell proliferation through a candidate tumor suppressor, Ptger4.
Murn, Jernej; Alibert, Olivier; Wu, Ning; Tendil, Simon; Gidrol, Xavier
2008-12-22
B cell receptor (BCR) signaling contributes to the pathogenesis of B cell malignancies, and most B cell lymphomas depend on BCR signals for survival. Identification of genes that restrain BCR-mediated proliferation is therefore an important goal toward improving the therapy of B cell lymphoma. Here, we identify Ptger4 as a negative feedback regulator of proliferation in response to BCR signals and show that its encoded EP4 receptor is a principal molecule conveying the growth-suppressive effect of prostaglandin E2 (PGE2). Stable knockdown of Ptger4 in B cell lymphoma markedly accelerated tumor spread in mice, whereas Ptger4 overexpression yielded significant protection. Mechanistically, we show that the intrinsic activity of Ptger4 and PGE2-EP4 signaling target a similar set of activating genes, and find Ptger4 to be significantly down-regulated in human B cell lymphoma. We postulate that Ptger4 functions in B cells as a candidate tumor suppressor whose activity is regulated by PGE2 in the microenvironment. These findings suggest that targeting EP4 receptor for prostaglandin may present a novel strategy for treatment of B cell malignancies.
Prostaglandin E2 regulates B cell proliferation through a candidate tumor suppressor, Ptger4
Murn, Jernej; Alibert, Olivier; Wu, Ning; Tendil, Simon; Gidrol, Xavier
2008-01-01
B cell receptor (BCR) signaling contributes to the pathogenesis of B cell malignancies, and most B cell lymphomas depend on BCR signals for survival. Identification of genes that restrain BCR-mediated proliferation is therefore an important goal toward improving the therapy of B cell lymphoma. Here, we identify Ptger4 as a negative feedback regulator of proliferation in response to BCR signals and show that its encoded EP4 receptor is a principal molecule conveying the growth-suppressive effect of prostaglandin E2 (PGE2). Stable knockdown of Ptger4 in B cell lymphoma markedly accelerated tumor spread in mice, whereas Ptger4 overexpression yielded significant protection. Mechanistically, we show that the intrinsic activity of Ptger4 and PGE2–EP4 signaling target a similar set of activating genes, and find Ptger4 to be significantly down-regulated in human B cell lymphoma. We postulate that Ptger4 functions in B cells as a candidate tumor suppressor whose activity is regulated by PGE2 in the microenvironment. These findings suggest that targeting EP4 receptor for prostaglandin may present a novel strategy for treatment of B cell malignancies. PMID:19075289
Containment of fertilizers and pesticides at retail operations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Broder, M.F.
1990-06-28
Environmental protection has become as important to the fertilizer retailer as the products and services he offers. Emphasis on environmental protection at the dealer level is largely in response to state regulations designed to protect groundwater. The national Clean Water Act of 1987 gave states the lead in developing groundwater protection strategies. Several states have adopted new or stronger regulations and others are moving to do so. Fertilizer dealers need to keep up with these regulations and promote groundwater protection. This paper describes several containment systems for fertilizers and pesticides to help dealers decide how to modify their plants tomore » protect groundwater.« less
A Consumer Protection Model for Regulating Lawyers.
ERIC Educational Resources Information Center
Chalfie, Deborah M.
1992-01-01
Describes and critiques the "discipline model" of lawyer regulation from a consumer point of view and outlines an alternative model for regulating lawyers that is grounded in consumer protection principles. (JOW)
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA review of State implementation of national primary drinking water regulations for lead and copper. 142.19 Section 142.19 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Primar...
Cai, Wen-Peng; Pan, Yu; Zhang, Shui-Miao; Wei, Cun; Dong, Wei; Deng, Guang-Hui
2017-10-01
The current study aimed to explore the association of cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers and to understand the multiple mediation effects of social support and resilience on the relationship between cognitive emotion regulation and acute stress responses. A total of 1477 male soldiers completed mental scales, including the cognitive emotion regulation questionnaire-Chinese version, the perceived social support scale, the Chinese version of the Connor-Davidson resilience scale, and the military acute stress scale. As hypothesized, physiological responses, psychological responses, and acute stress were associated with negative-focused cognitive emotion regulation, and negatively associated with positive-focused cognitive emotion regulation, social supports and resilience. Besides, positive-focused cognitive emotion regulation, social support, and resilience were significantly associated with one another, and negative-focused cognitive emotion regulation was negatively associated with social support. Regression analysis and bootstrap analysis showed that social support and resilience had partly mediating effects on negative strategies and acute stress, and fully mediating effects on positive strategies and acute stress. These results thus indicate that military acute stress is significantly associated with cognitive emotion regulation, social support, and resilience, and that social support and resilience have multiple mediation effects on the relationship between cognitive emotion regulation and acute stress responses. Copyright © 2017 Elsevier B.V. All rights reserved.
Gene regulation system of vasopressin and corticotropin-releasing hormone.
Yoshida, Masanori
2008-03-03
The neurohypophyseal hormones, arginine vasopressin and corticotropin-releasing hormone (CRH), play a crucial role in the physiological and behavioral response to various kinds of stresses. Both neuropeptides activate the hypophysial-pituitary-adrenal (HPA) axis, which is a central mediator of the stress response in the body. Conversely, they receive the negative regulation by glucocorticoid, which is an end product of the HPA axis. Vasopressin and CRH are closely linked to immune response; they also interact with pro-inflammatory cytokines. Moreover, as for vasopressin, it has another important role, which is the regulation of water balance through its potent antidiuretic effect. Hence, it is conceivable that vasopressin and CRH mediate the homeostatic responses for survival and protect organisms from the external world. A tight and elaborate regulation system of the vasopressin and CRH gene is required for the rapid and flexible response to the alteration of the surrounding environments. Several important regulatory elements have been identified in the proximal promoter region in the vasopressin and CRH gene. Many transcription factors and intracellular signaling cascades are involved in the complicated gene regulation system. This review focuses on the current status of the basic research of vasopressin and CRH. In addition to the numerous known facts about their divergent physiological roles, the recent topics of promoter analyses will be discussed.
A model of organisational dysfunction in the NHS.
Pope, Rachael
2013-01-01
This paper explores the reasons for the sometimes seemingly irrational and dysfunctional organisational behaviour within the NHS. It seeks to provide possible answers to the persistent historical problem of intimidating and negative behaviour between staff, and the sometimes inadequate organisational responses. The aim is to develop a model to explain and increase understanding of such behaviour in the NHS. This paper is conceptual in nature based upon a systematic literature review. The concepts of organisational silence, normalised organisational corruption, and protection of image, provide some possible answers for these dysfunctional responses, as does the theory of selective moral disengagement. The NHS exhibits too high a level of collective ego defences and protection of its image and self-esteem, which distorts its ability to address problems and to learn. Organisations and the individuals within them can hide and retreat from reality and exhibit denial; there is a resistance to voice and to "knowing". The persistence and tolerance of negative behaviour is a corruption and is not healthy or desirable. Organisations need to embrace the identity of a listening and learning organisation; a "wise" organisation. The "Elephant in the room" of persistent negative behaviour has to be acknowledged; the silence must be broken. There is a need for cultures of "respect", exhibiting "intelligent kindness". A model has been developed to increase understanding of dysfunctional organisational behaviour in the NHS primarily for leaders/managers of health services, health service regulators and health researchers/academics. Research, with ethical approval, is currently being undertaken to test and develop the conceptual model to further reflect the complexities of the NHS culture.
Choi, Tae Gyu; Nguyen, Minh Nam; Kim, Jieun; Jo, Yong Hwa; Jang, Miran; Nguyen, Ngoc Ngo Yen; Yun, Hyeong Rok; Choe, Wonchae; Kang, Insug; Ha, Joohun; Tang, Dean G; Kim, Sung Soo
2018-06-06
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Chemoresistance is a major problem for effective therapy in CRC. Here, we investigated the mechanism by which peptidylprolyl isomerase B (PPIB; cyclophilin B, CypB) regulates chemoresistance in CRC. We found that CypB is a novel wild type p53 (p53WT)-inducible gene but a negative regulator of p53WT in response to oxaliplatin treatment. Overexpression of CypB shortens the half-life of p53WT and inhibits oxaliplatin-induced apoptosis in CRC cells, whereas knockdown of CypB lengthens the half-life of p53WT and stimulates p53WT dependent apoptosis. CypB interacts directly with MDM2, and enhances MDM2-dependent p53WT ubiquitination and degradation. Furthermore, we firmly validated using bioinformatics analyses that overexpression of CypB is associated with poor prognosis in CRC progression and chemoresistance. Hence, we suggest a novel mechanism of chemoresistance caused by overexpressed CypB, which may help to develop new anti-cancer drugs. We also propose that CypB may be utilized as a predictive biomarker in CRC patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
40 CFR 141.500 - General requirements.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 141.500 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Filtration and Disinfection-Systems Serving... subpart constitute national primary drinking water regulations. These regulations establish requirements...
40 CFR 141.170 - General requirements.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 141.170 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Filtration and Disinfection-Systems Serving... constitute national primary drinking water regulations. These regulations establish requirements for...
40 CFR 141.700 - General requirements.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 141.700 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Treatment for Cryptosporidium General... drinking water regulations. The regulations in this subpart establish or extend treatment technique...
40 CFR 141.700 - General requirements.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 141.700 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Treatment for Cryptosporidium General... drinking water regulations. The regulations in this subpart establish or extend treatment technique...
40 CFR 141.700 - General requirements.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 141.700 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Treatment for Cryptosporidium General... drinking water regulations. The regulations in this subpart establish or extend treatment technique...
40 CFR 141.700 - General requirements.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 141.700 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Treatment for Cryptosporidium General... drinking water regulations. The regulations in this subpart establish or extend treatment technique...
Code of Federal Regulations, 2010 CFR
2010-10-01
... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Disclosure, protection, and... 1503.104-5 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY GENERAL IMPROPER BUSINESS PRACTICES AND PERSONAL CONFLICTS OF INTEREST Safeguards 1503.104-5 Disclosure, protection, and...
Dadson, Keith; Hauck, Ludger; Hao, Zhenyue; Grothe, Daniela; Rao, Vivek; Mak, Tak W; Billia, Filio
2017-02-02
Cardiac homeostasis requires proper control of protein turnover. Protein degradation is principally controlled by the Ubiquitin-Proteasome System. Mule is an E3 ubiquitin ligase that regulates cellular growth, DNA repair and apoptosis to maintain normal tissue architecture. However, Mule's function in the heart has yet to be described. In a screen, we found reduced Mule expression in left ventricular samples from end-stage heart failure patients. Consequently, we generated conditional cardiac-specific Mule knockout (Mule fl/fl(y) ;mcm) mice. Mule ablation in adult Mule fl/fl(y) ;mcm mice prevented myocardial c-Myc polyubiquitination, leading to c-Myc accumulation and subsequent reduced expression of Pgc-1α, Pink1, and mitochondrial complex proteins. Furthermore, these mice developed spontaneous cardiac hypertrophy, left ventricular dysfunction, and early mortality. Co-deletion of Mule and c-Myc rescued this phenotype. Our data supports an indispensable role for Mule in cardiac homeostasis through the regulation of mitochondrial function via maintenance of Pgc-1α and Pink1 expression and persistent negative regulation of c-Myc.
Matrix exopolysaccharides; the sticky side of biofilm formation.
Maunders, Eve; Welch, Martin
2017-07-06
The Gram-negative pathogen Pseudomonas aeruginosa is found ubiquitously within the environment and is recognised as an opportunistic human pathogen that commonly infects burn wounds and immunocompromised individuals, or patients suffering from the autosomal recessive disorder cystic fibrosis (CF). During chronic infection, P. aeruginosa is thought to form structured aggregates known as biofilms characterised by a self-produced matrix which encases the bacteria, protecting them from antimicrobial attack and the host immune response. In many cases, antibiotics are ineffective at eradicating P. aeruginosa from chronically infected CF airways. Cyclic-di-GMP has been identified as a key regulator of biofilm formation; however, the way in which its effector proteins elicit a change in biofilm formation remains unclear. Identifying regulators of biofilm formation is a key theme of current research and understanding the factors that activate biofilm formation may help to expose potential new drug targets that slow the onset of chronic infection. This minireview outlines the contribution made by exopolysaccharides to biofilm formation, and describes the current understanding of biofilm regulation in P. aeruginosa with a particular focus on CF airway-associated infections. © FEMS 2017.
Neural correlates of preparatory and regulatory control over positive and negative emotion.
Seo, Dongju; Olman, Cheryl A; Haut, Kristen M; Sinha, Rajita; MacDonald, Angus W; Patrick, Christopher J
2014-04-01
This study used functional magnetic resonance imaging to investigate brain activation during preparatory and regulatory control while participants (N = 24) were instructed either to simply view or decrease their emotional response to, pleasant, neutral or unpleasant pictures. A main effect of emotional valence on brain activity was found in the right precentral gyrus, with greater activation during positive than negative emotion regulation. A main effect of regulation phase was evident in the bilateral anterior prefrontal cortex (PFC), precuneus, posterior cingulate cortex, right putamen and temporal and occipital lobes, with greater activity in these regions during preparatory than regulatory control. A valence X regulation interaction was evident in regions of ventromedial PFC and anterior cingulate cortex, reflecting greater activation while regulating negative than positive emotion, but only during active emotion regulation (not preparation). Conjunction analyses revealed common brain regions involved in differing types of emotion regulation including selected areas of left lateral PFC, inferior parietal lobe, temporal lobe, right cerebellum and bilateral dorsomedial PFC. The right lateral PFC was additionally activated during the modulation of both positive and negative valence. Findings demonstrate significant modulation of brain activity during both preparation for, and active regulation of positive and negative emotional states.
Duzyj, Christina M; Paidas, Michael J; Jebailey, Lellean; Huang, Jing Shun; Barnea, Eytan R
2014-01-01
Intimate embryo-maternal interaction is paramount for pregnancy success post-implantation. The embryo follows a specific developmental timeline starting with neural system, dependent on endogenous and decidual factors. Beyond altered genetics/epigenetics, post-natal diseases may initiate at prenatal/neonatal, post-natal period, or through a continuum. Preimplantation factor (PIF) secreted by viable embryos promotes implantation and trophoblast invasion. Synthetic PIF reverses neuroinflammation in non-pregnant models. PIF targets embryo proteins that protect against oxidative stress and protein misfolding. We report of PIF's embryotrophic role and potential to prevent developmental disorders by regulating uterine milieu at implantation and first trimester. PIF's effect on human implantation (human endometrial stromal cells (HESC)) and first-trimester decidua cultures (FTDC) was examined, by global gene expression (Affymetrix), disease-biomarkers ranking (GeneGo), neuro-specific genes (Ingenuity) and proteins (mass-spectrometry). PIF co-cultured epidermal growth factor (EGF) in both HESC and FTDC (Affymetrix) was evaluated. In HESC, PIF promotes neural differentiation and transmission genes (TLX2, EPHA10) while inhibiting retinoic acid receptor gene, which arrests growth. PIF promotes axon guidance and downregulates EGF-dependent neuroregulin signaling. In FTDC, PIF promotes bone morphogenetic protein pathway (SMAD1, 53-fold) and axonal guidance genes (EPH5) while inhibiting PPP2R2C, negative cell-growth regulator, involved in Alzheimer's and amyotrophic lateral sclerosis. In HESC, PIF affects angiotensin via beta-arrestin, transforming growth factor-beta (TGF-β), notch, BMP, and wingless-int (WNT) signaling pathways that promote neurogenesis involved in childhood neurodevelopmental diseases-autism and also affected epithelial-mesenchymal transition involved in neuromuscular disorders. In FTDC, PIF upregulates neural development and hormone signaling, while downregulating genes protecting against xenobiotic response leading to connective tissue disorders. In both HESC and FTDC, PIF affects neural development and transmission pathways. In HESC interactome, PIF promotes FUS gene, which controls genome integrity, while in FTDC, PIF upregulates STAT3 critical transcription signal. EGF abolished PIF's effect on HESC, decreasing metalloproteinase and prolactin receptor genes, thereby interfering with decidualization, while in FTDC, EGF co-cultured with PIF reduced ZHX2, gene that regulates neural AFP secretion. PIF promotes decidual trophic genes and proteins to regulate neural development. By regulating the uterine milieu, PIF may decrease embryo vulnerability to post-natal neurodevelopmental disorders. Examination of PIF-based intervention strategies used during embryogenesis to improve pregnancy prognosis and reduce post-natal vulnerability is clearly in order.
2014-01-01
Background Intimate embryo-maternal interaction is paramount for pregnancy success post-implantation. The embryo follows a specific developmental timeline starting with neural system, dependent on endogenous and decidual factors. Beyond altered genetics/epigenetics, post-natal diseases may initiate at prenatal/neonatal, post-natal period, or through a continuum. Preimplantation factor (PIF) secreted by viable embryos promotes implantation and trophoblast invasion. Synthetic PIF reverses neuroinflammation in non-pregnant models. PIF targets embryo proteins that protect against oxidative stress and protein misfolding. We report of PIF’s embryotrophic role and potential to prevent developmental disorders by regulating uterine milieu at implantation and first trimester. Methods PIF’s effect on human implantation (human endometrial stromal cells (HESC)) and first-trimester decidua cultures (FTDC) was examined, by global gene expression (Affymetrix), disease-biomarkers ranking (GeneGo), neuro-specific genes (Ingenuity) and proteins (mass-spectrometry). PIF co-cultured epidermal growth factor (EGF) in both HESC and FTDC (Affymetrix) was evaluated. Results In HESC, PIF promotes neural differentiation and transmission genes (TLX2, EPHA10) while inhibiting retinoic acid receptor gene, which arrests growth. PIF promotes axon guidance and downregulates EGF-dependent neuroregulin signaling. In FTDC, PIF promotes bone morphogenetic protein pathway (SMAD1, 53-fold) and axonal guidance genes (EPH5) while inhibiting PPP2R2C, negative cell-growth regulator, involved in Alzheimer’s and amyotrophic lateral sclerosis. In HESC, PIF affects angiotensin via beta-arrestin, transforming growth factor-beta (TGF-β), notch, BMP, and wingless-int (WNT) signaling pathways that promote neurogenesis involved in childhood neurodevelopmental diseases—autism and also affected epithelial-mesenchymal transition involved in neuromuscular disorders. In FTDC, PIF upregulates neural development and hormone signaling, while downregulating genes protecting against xenobiotic response leading to connective tissue disorders. In both HESC and FTDC, PIF affects neural development and transmission pathways. In HESC interactome, PIF promotes FUS gene, which controls genome integrity, while in FTDC, PIF upregulates STAT3 critical transcription signal. EGF abolished PIF’s effect on HESC, decreasing metalloproteinase and prolactin receptor genes, thereby interfering with decidualization, while in FTDC, EGF co-cultured with PIF reduced ZHX2, gene that regulates neural AFP secretion. Conclusions PIF promotes decidual trophic genes and proteins to regulate neural development. By regulating the uterine milieu, PIF may decrease embryo vulnerability to post-natal neurodevelopmental disorders. Examination of PIF-based intervention strategies used during embryogenesis to improve pregnancy prognosis and reduce post-natal vulnerability is clearly in order. PMID:26085845
Convergent spray process for environmentally friendly coatings
NASA Technical Reports Server (NTRS)
Scarpa, Jack
1995-01-01
Conventional spray application processes have poor transfer efficiencies, resulting in an exorbitant loss in materials, solvents, and time. Also, with ever tightening Environmental Protection Agency (EPA) regulations and Occupational Safety and Health Administration requirements, the low transfer efficiencies have a significant impact on the quantities of materials and solvents that are released into the environment. High solids spray processes are also limited by material viscosities, thus requiring many passes over the surface to achieve a thickness in the 0.125 -inch range. This results in high application costs and a negative impact on the environment. Until recently, requirements for a 100 percent solid sprayable, environmentally friendly, lightweight thermal protection system that can be applied in a thick (greater than 0.125 inch) single-pass operation exceeded the capability of existing systems. Such coatings must be applied by hand lay-up techniques, especially for thermal and/or fire protection systems. The current formulation of these coatings has presented many problems such as worker safety, environmental hazards, waste, high cost, and application constraints. A system which can apply coatings without using hazardous materials would alleviate many of these problems. Potential applications include the aerospace thermal protective specialty coatings, chemical and petroleum industries that require fire-protection coatings that resist impact, chemicals, and weather. These markets can be penetrated by offering customized coatings applied by automated processes that are environmentally friendly.
Dettman, Robert W.; Birch, Derin; Fernando, Augusta; Kessler, John A.; Dizon, Maria L.V.
2018-01-01
Hypoxic-ischemic injury (HI) to the neonatal human brain results in myelin loss that, in some children, can manifest as cerebral palsy. Previously, we had found that neuronal overexpression of the bone morphogenic protein (BMP) inhibitor noggin during development increased oligodendroglia and improved motor function in an experimental model of HI utilizing unilateral common carotid artery ligation followed by hypoxia. As BMPs are known to negatively regulate oligodendroglial fate specification of neural stem cells and alter differentiation of committed oligodendroglia, BMP signaling is likely an important mechanism leading to myelin loss. Here, we showed that BMP signaling is upregulated within oligodendroglia of the neonatal brain. We tested the hypothesis that inhibition of BMP signaling specifically within neural progenitor cells (NPCs) is sufficient to protect oligodendroglia. We conditionally deleted the BMP receptor 2 subtype (BMPR2) in NG2-expressing cells after HI. We found that BMPR2 deletion globally protects the brain as assessed by MRI and protects motor function as assessed by digital gait analysis, and that conditional deletion of BMPR2 maintains oligodendrocyte marker expression by immunofluorescence and Western blot and prevents loss of oligodendroglia. Finally, BMPR2 deletion after HI results in an increase in noncompacted myelin. Thus, our data indicate that inhibition of BMP signaling specifically in NPCs may be a tractable strategy to protect the newborn brain from HI. PMID:29324456
Leung, Chi K.; Wang, Ying; Deonarine, Andrew; Tang, Lanlan; Prasse, Stephanie
2013-01-01
Negative-feedback loops between transcription factors and repressors in responses to xenobiotics, oxidants, heat, hypoxia, DNA damage, and infection have been described. Although common, the function of feedback is largely unstudied. Here, we define a negative-feedback loop between the Caenorhabditis elegans detoxification/antioxidant response factor SKN-1/Nrf and its repressor wdr-23 and investigate its function in vivo. Although SKN-1 promotes stress resistance and longevity, we find that tight regulation by WDR-23 is essential for growth and reproduction. By disabling SKN-1 transactivation of wdr-23, we reveal that feedback is required to set the balance between growth/reproduction and stress resistance/longevity. We also find that feedback is required to set the sensitivity of a core SKN-1 target gene to an electrophile. Interestingly, the effect of feedback on target gene induction is greatly reduced when the stress response is strongly activated, presumably to ensure maximum activation of cytoprotective genes during potentially fatal conditions. Our work provides a framework for understanding the function of negative feedback in inducible stress responses and demonstrates that manipulation of feedback alone can shift the balance of competing animal processes toward cell protection, health, and longevity. PMID:23836880
Situation Selection and Modification for Emotion Regulation in Younger and Older Adults
Livingstone, Kimberly M.; Isaacowitz, Derek M.
2016-01-01
This research investigated age differences in use and effectiveness of situation selection and situation modification for emotion regulation. Socioemotional selectivity theory suggests stronger emotional well-being goals in older age; emotion regulation may support this goal. Younger and older adults assigned to an emotion regulation or “just view” condition first freely chose to engage with negative, neutral, or positive material (situation selection), then chose to view or skip negative and positive material (situation modification), rating affect after each experience. In both tasks, older adults in both goal conditions demonstrated pro-hedonic emotion regulation, spending less time with negative material compared to younger adults. Younger adults in the regulate condition also engaged in pro-hedonic situation selection, but not modification. Whereas situation selection was related to affect, modification of negative material was not. This research supports more frequent pro-hedonic motivation in older age, as well as age differences in use of early-stage emotion regulation. PMID:26998196
Mobile Phone Use, Emotion Regulation, and Well-Being.
Hoffner, Cynthia A; Lee, Sangmi
2015-07-01
This study examined the use of mobile phones to regulate negative emotions, considering both the role of different aspects of phone use and individual differences in emotion regulation strategies. A total of 287 young adult smartphone users completed an online survey that addressed use of mobile phones for negative emotion regulation. They responded to a phone loss scenario by rating how much they would miss various uses/functions of the phone (which could be involved in emotion regulation). Habitual use of reappraisal to regulate emotion was associated with missing both interpersonal contact and social support, but not access to entertainment/information. In contrast, habitual use of emotion suppression was associated only with missing entertainment/information content. Regulating negative emotions via mobile phone was associated with missing all three uses/functions of the phone, but perception that the phone was effective in remediating negative emotion was associated only with missing social support. Well-being was related to greater use and perceived effectiveness of the mobile phone for emotion regulation. Overall, this study demonstrates that mobile phones can yield psychological benefits, depending on how they are used. Findings suggest that using the phone for social support is most likely to lead to effective remediation of negative emotion. Interpretations and implications of the findings are discussed.
40 CFR 141.620 - General requirements.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 141.620 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Stage 2 Disinfection Byproducts Requirements § 141... primary drinking water regulations. The regulations in this subpart establish monitoring and other...
Johnson, Adrienne L; McLeish, Alison C
2016-02-01
Although negative affect is associated with a number of smoking-related cognitive processes, the mechanisms underlying these associations have yet to be examined. The current study sought to examine the indirect effect of emotion regulation difficulties in terms of the association between negative affect and smoking-related cognitive processes (internal barriers to cessation, negative affect reduction smoking motives, negative affect reduction smoking outcome expectancies). Participants were 126 daily cigarette smokers (70.4% male, Mage=36.5years, SD=13.0; 69.8% Caucasian) who smoked an average of 18.5 (SD=8.7) cigarettes per day and reported moderate nicotine dependence. Formal mediation analyses were conducted using PROCESS to examine the indirect effect of negative affect on internal barriers to cessation and negative affect reduction smoking motives and outcome expectancies through emotion regulation difficulties. After accounting for the effects of gender, daily smoking rate, and anxiety sensitivity, negative affect was indirectly related to internal barriers to cessation and negative affect reduction smoking motives through emotion regulation difficulties. There was no significant indirect effect for negative affect reduction smoking outcome expectancies. These findings suggest that greater negative affect is associated with a desire to smoke to reduce this negative affect and perceptions that quitting smoking will be difficult due to negative emotions because of greater difficulties managing these negative emotions. Thus, emotion regulation difficulties may be an important target for smoking cessation interventions. Copyright © 2015 Elsevier Ltd. All rights reserved.
Wu, Kaifeng; Xu, Hongmei; Zheng, Yuqiang; Wang, Libin; Zhang, Xuemei; Yin, Yibing
2016-07-08
Transcriptional regulation of capsule expression is critical for pneumococcal transition from carriage to infection, yet the underlying mechanism remains incompletely understood. Here, we describe the regulation of capsular polysaccharide, one of the most important pneumococcal virulence factor by a GntR family regulator, CpsR. Electrophoretic mobility-shift assays have shown the direct interaction between CpsR and the cps promoter (cpsp), and their interaction could be competitively interfered by glucose. DNase I footprinting assays localized the binding site to a region -146 to -114 base pairs relative to the transcriptional start site of the cps locus in S. pneumoniae D39. We found that CpsR negatively controlled the transcription of the cps locus and hence CPS production, which was confirmed by fine-tuning expression of CpsR in a ΔcpsR complemented strain. Increased expression of CpsR in complemented strain led to a decreased resistance to the whole-blood-mediated killing, suggesting a protective role for CpsR-cpsp interaction in the establishment of invasive infection. Finally, animal experiments showed that CpsR-cpsp interaction was necessary for both pneumococcal colonization and invasive infection. Taken together, our results provide a thorough insight into the regulation of capsule production mediated by CpsR and its important roles in pneumococcal pathogenesis.
Fisher, Naomi R; Mead, Bethan R; Lattimore, Paul; Malinowski, Peter
2017-11-01
Evidence regarding the effectiveness of mindfulness based interventions (MBIs) for eating disorders, weight management and food craving is emerging and further studies are required to understand the underlying mechanisms of MBIs in these domains. The current study was designed to establish the role of specific mechanisms underlying the putative relationship between mindfulness and reward motivated eating. We predicted that mindfulness would be negatively related to features of reward motivated eating and that this association would be mediated by emotion regulation and habitual negative self-thinking. A cross-sectional survey measuring uncontrolled and emotional eating, mindfulness, emotion regulation and habitual negative self-thinking was completed by female and male meditators and non-meditators (N = 632). Lower levels of dispositional mindfulness were associated with difficulties in emotion regulation, habitual negative self-thinking and both emotional and uncontrolled eating. Difficulties in emotion regulation significantly mediated the mindfulness-uncontrolled eating relationship. Habitual negative self-thinking significantly mediated the mindfulness-emotional eating relationship. Participants with meditation experience reported greater levels of dispositional mindfulness, fewer difficulties with emotion regulation and habitual negative self-thinking and reduced uncontrolled eating tendencies, compared to non-meditators. The findings suggest that MBIs designed to change reward motivated eating and weight control should focus on emotion regulation and mental habits as underlying mechanisms. Copyright © 2017. Published by Elsevier Ltd.
40 CFR 62.7852 - Identification of plan-negative declaration.
Code of Federal Regulations, 2014 CFR
2014-07-01
... Mexico Fluoride Emissions from Primary Aluminum Plants § 62.7852 Identification of plan—negative declaration. The New Mexico Environmental Improvement Division and the Albuquerque Air Pollution Control... declaration. 62.7852 Section 62.7852 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...
40 CFR 62.7852 - Identification of plan-negative declaration.
Code of Federal Regulations, 2012 CFR
2012-07-01
... Mexico Fluoride Emissions from Primary Aluminum Plants § 62.7852 Identification of plan—negative declaration. The New Mexico Environmental Improvement Division and the Albuquerque Air Pollution Control... declaration. 62.7852 Section 62.7852 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...
40 CFR 62.7852 - Identification of plan-negative declaration.
Code of Federal Regulations, 2013 CFR
2013-07-01
... Mexico Fluoride Emissions from Primary Aluminum Plants § 62.7852 Identification of plan—negative declaration. The New Mexico Environmental Improvement Division and the Albuquerque Air Pollution Control... declaration. 62.7852 Section 62.7852 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...
40 CFR 62.7852 - Identification of plan-negative declaration.
Code of Federal Regulations, 2011 CFR
2011-07-01
... Mexico Fluoride Emissions from Primary Aluminum Plants § 62.7852 Identification of plan—negative declaration. The New Mexico Environmental Improvement Division and the Albuquerque Air Pollution Control... declaration. 62.7852 Section 62.7852 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...
40 CFR 62.7852 - Identification of plan-negative declaration.
Code of Federal Regulations, 2010 CFR
2010-07-01
... Mexico Fluoride Emissions from Primary Aluminum Plants § 62.7852 Identification of plan—negative declaration. The New Mexico Environmental Improvement Division and the Albuquerque Air Pollution Control... declaration. 62.7852 Section 62.7852 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...
15 CFR 30.17 - Customs and Border Protection regulations.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Customs and Border Protection regulations. 30.17 Section 30.17 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade BUREAU OF THE CENSUS, DEPARTMENT OF COMMERCE FOREIGN TRADE REGULATIONS Export Control and Licensing...
40 CFR Appendix A to Subpart A of... - State Regulation of Nonroad Internal Combustion Engines
Code of Federal Regulations, 2012 CFR
2012-07-01
... 40 Protection of Environment 21 2012-07-01 2012-07-01 false State Regulation of Nonroad Internal Combustion Engines A Appendix A to Subpart A of Part 89 Protection of Environment ENVIRONMENTAL PROTECTION... Nonroad Internal Combustion Engines This appendix sets forth the Environmental Protection Agency's (EPA's...
40 CFR Appendix A to Subpart A of... - State Regulation of Nonroad Internal Combustion Engines
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 20 2010-07-01 2010-07-01 false State Regulation of Nonroad Internal Combustion Engines A Appendix A to Subpart A of Part 89 Protection of Environment ENVIRONMENTAL PROTECTION... Nonroad Internal Combustion Engines This appendix sets forth the Environmental Protection Agency's (EPA's...
40 CFR Appendix A to Subpart A of... - State Regulation of Nonroad Internal Combustion Engines
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 20 2011-07-01 2011-07-01 false State Regulation of Nonroad Internal Combustion Engines A Appendix A to Subpart A of Part 89 Protection of Environment ENVIRONMENTAL PROTECTION... Nonroad Internal Combustion Engines This appendix sets forth the Environmental Protection Agency's (EPA's...
40 CFR Appendix A to Subpart A of... - State Regulation of Nonroad Internal Combustion Engines
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 21 2013-07-01 2013-07-01 false State Regulation of Nonroad Internal Combustion Engines A Appendix A to Subpart A of Part 89 Protection of Environment ENVIRONMENTAL PROTECTION... Nonroad Internal Combustion Engines This appendix sets forth the Environmental Protection Agency's (EPA's...
40 CFR Appendix A to Subpart A of... - State Regulation of Nonroad Internal Combustion Engines
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 20 2014-07-01 2013-07-01 true State Regulation of Nonroad Internal Combustion Engines A Appendix A to Subpart A of Part 89 Protection of Environment ENVIRONMENTAL PROTECTION... Nonroad Internal Combustion Engines This appendix sets forth the Environmental Protection Agency's (EPA's...
Pastor-Ciurana, Jordi; Rabasa, Cristina; Ortega-Sánchez, Juan A; Sanchís-Ollè, Maria; Gabriel-Salazar, Marina; Ginesta, Marta; Belda, Xavier; Daviu, Núria; Nadal, Roser; Armario, Antonio
2014-05-15
Exposure to chronic unpredictable stress (CUS) is gaining acceptance as a putative animal model of depression. However, there is evidence that chronic exposure to stress can offer non-specific stress protection from some effects of acute superimposed stressors. We then compared in adult male rats the protection afforded by prior exposure to CUS with the one offered by repeated immobilization on boards (IMO) regarding some of the negative consequences of an acute exposure to IMO. Repeated exposure to IMO protected from the negative consequences of an acute IMO on activity in an open-field, saccharin intake and body weight gain. Active coping during IMO (struggling) was markedly reduced by repeated exposure to the same stressor, but it was not affected by a prior history of CUS, suggesting that our CUS protocol does not appear to impair active coping responses. CUS exposure itself caused a strong reduction of activity in the open-field but appeared to protect from the hypo-activity induced by acute IMO. Moreover, prior CUS offered partial protection from acute IMO-induced reduction of saccharin intake and body weight gain. It can be concluded that a prior history of CUS protects from some of the negative consequences of exposure to a novel severe stressor, suggesting the development of partial cross-adaptation whose precise mechanisms remain to be studied. Copyright © 2014 Elsevier B.V. All rights reserved.
Sung, Sharon C.; Porter, Eliora; Robinaugh, Donald J.; Marks, Elizabeth H.; Marques, Luana M.; Otto, Michael W.; Pollack, Mark H.; Simon, Naomi M.
2014-01-01
The present study examined negative mood regulation expectancies, anxiety symptom severity, and quality of life in a sample of 167 patients with social anxiety disorder (SAD) and 165 healthy controls with no DSM-IV Axis I disorders. Participants completed the Generalized Expectancies for Negative Mood Regulation Scale (NMR), the Beck Anxiety Inventory, and the Quality of Life Enjoyment and Satisfaction Questionnaire. SAD symptom severity was assessed using the Liebowitz Social Anxiety Scale. Individuals with SAD scored significantly lower than controls on the NMR. Among SAD participants, NMR scores were negatively correlated with anxiety symptoms and SAD severity, and positively correlated with quality of life. NMR expectancies positively predicted quality of life even after controlling for demographic variables, comorbid diagnoses, anxiety symptoms, and SAD severity. Individuals with SAD may be less likely to engage in emotion regulating strategies due to negative beliefs regarding their effectiveness, thereby contributing to poorer quality of life. PMID:22343166
29 CFR 1926.100 - Head protection.
Code of Federal Regulations, 2014 CFR
2014-07-01
... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Personal Protective and Life Saving Equipment... Industrial Head Protection,” incorporated by reference in § 1926.6; (ii) American National Standards...
29 CFR 1926.100 - Head protection.
Code of Federal Regulations, 2013 CFR
2013-07-01
... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Personal Protective and Life Saving Equipment... Industrial Head Protection,” incorporated by reference in § 1926.6; (ii) American National Standards...
Greening, Steven G.; Osuch, Elizabeth A.; Williamson, Peter C.
2014-01-01
Depressive cognitive schemas play an important role in the emergence and persistence of major depressive disorder (MDD). The current study adapted emotion regulation techniques to reflect elements of cognitive behavioural therapy (CBT) and related psychotherapies to delineate neurocognitive abnormalities associated with modulating the negative cognitive style in MDD. Nineteen non-medicated patients with MDD and 19 matched controls reduced negative or enhanced positive feelings elicited by emotional scenes while undergoing functional magnetic resonance imaging. Although both groups showed significant emotion regulation success as measured by subjective ratings of affect, the controls were significantly better at modulating both negative and positive emotion. Both groups recruited regions of dorsolateral prefrontal cortex and ventrolateral prefrontal cortex (VLPFC) when regulating negative emotions. Only in controls was this accompanied by reduced activity in sensory cortices and amygdala. Similarly, both groups showed enhanced activity in VLPFC and ventral striatum when enhancing positive affect; however, only in controls was ventral striatum activity correlated with regulation efficacy. The results suggest that depression is associated with both a reduced capacity to achieve relief from negative affect despite recruitment of ventral and dorsal prefrontal cortical regions implicated in emotion regulation, coupled with a disconnect between activity in reward-related regions and subjective positive affect. PMID:23482626
Miller, Alison L.; Song, Ju-Hyun; Sturza, Julie; Lumeng, Julie C.; Rosenblum, Katherine; Kaciroti, Niko; Vazquez, Delia M.
2018-01-01
Biological and social influences both shape emotion regulation. In 380 low-income children, we tested whether biological stress profile (cortisol) moderated the association among positive and negative home environment factors (routines; chaos) and emotion regulation (negative lability; positive regulation). Children (M age = 50.6, SD = 6.4 months) provided saliva samples to assess diurnal cortisol parameters across 3 days. Parents reported on home environment and child emotion regulation. Structural equation modeling was used to test whether cortisol parameters moderated associations between home environment and child emotion regulation. Results showed that home chaos was negatively associated with emotion regulation outcomes; cortisol did not moderate the association. Child cortisol level moderated the routines-emotion regulation association such that lack of routine was most strongly associated with poor emotion regulation among children with lower cortisol output. Findings suggest that underlying child stress biology may shape response to environmental influences. PMID:27594200
Regulatory and Methodical Support of the Transition to the BATs in Heat Power Engineering
NASA Astrophysics Data System (ADS)
Roslyakov, P. V.; Kondrat'eva, O. E.; Borovkova, A. M.
2018-05-01
Federal Law no. 219-FZ of July 21, 2014, "On the Amendments to the Federal Law On Environmental Protection and Certain Legislative Acts" of the Russian Federation established new principles of environmental policy aimed at significantly reducing the negative anthropogenic impact on the environment. Currently, active work is under way to harmonize the Russian environmental legislation with regard to the transition to a system of technological regulation of impacts using the best available technologies (BATs). A national regulatory system based on BATs can be developed only through the implementation of integrated measures that are adopted and regulated at different levels (from decisions of the government of the Russian Federation to normative documents). For this purpose, more than 50 sectoral information and technical reference books on BATs have been developed that include descriptions of BATs for particular types of activities and their technological indicators. Starting on January 1, 2019, an integrated environmental permit will be introduced for enterprises with the greatest negative impact on the environment (category I enterprises). In addition, these enterprises will have to implement automatic systems for continuous control and metering of contaminants emissions (ASCCMCEs) into the atmosphere. Therefore, the development and adoption of the preliminary national standard of the Russian Federation PNS 187-2017, which is to come into force on January 1, 2018, will significantly accelerate and facilitate the implementation of ASCCMCEs of thermal power plants (TPPs) in accordance with Federal Law no. 219-FZ. The main goal of implementing ASCCMCEs on TPPs is to consistently reduce the negative impact of thermal power plants on the environment.
40 CFR 62.7860 - Identification of sources-negative declaration.
Code of Federal Regulations, 2013 CFR
2013-07-01
... Mexico Emissions from Existing Large Municipal Waste Combustion Units § 62.7860 Identification of sources—negative declaration. Letter from the City of Albuquerque Air Pollution Control Division dated September 10... declaration. 62.7860 Section 62.7860 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...
40 CFR 62.7860 - Identification of sources-negative declaration.
Code of Federal Regulations, 2012 CFR
2012-07-01
... Mexico Emissions from Existing Large Municipal Waste Combustion Units § 62.7860 Identification of sources—negative declaration. Letter from the City of Albuquerque Air Pollution Control Division dated September 10... declaration. 62.7860 Section 62.7860 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...
40 CFR 62.7854 - Identification of plan-negative declaration.
Code of Federal Regulations, 2012 CFR
2012-07-01
... of this chapter. (b) Letter from the City of Albuquerque Air Pollution Control Division dated... declaration. 62.7854 Section 62.7854 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Mexico Fluoride Emissions from Phosphate Fertilizer Plants § 62.7854 Identification of plan—negative...
40 CFR 62.7860 - Identification of sources-negative declaration.
Code of Federal Regulations, 2014 CFR
2014-07-01
... Mexico Emissions from Existing Large Municipal Waste Combustion Units § 62.7860 Identification of sources—negative declaration. Letter from the City of Albuquerque Air Pollution Control Division dated September 10... declaration. 62.7860 Section 62.7860 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...
40 CFR 62.7854 - Identification of plan-negative declaration.
Code of Federal Regulations, 2014 CFR
2014-07-01
... of this chapter. (b) Letter from the City of Albuquerque Air Pollution Control Division dated... declaration. 62.7854 Section 62.7854 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Mexico Fluoride Emissions from Phosphate Fertilizer Plants § 62.7854 Identification of plan—negative...
40 CFR 62.7854 - Identification of plan-negative declaration.
Code of Federal Regulations, 2013 CFR
2013-07-01
... of this chapter. (b) Letter from the City of Albuquerque Air Pollution Control Division dated... declaration. 62.7854 Section 62.7854 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Mexico Fluoride Emissions from Phosphate Fertilizer Plants § 62.7854 Identification of plan—negative...
Halliwell, Emma
2013-09-01
This article examines whether positive body image can protect women from negative media exposure effects. University women (N=112) were randomly allocated to view advertisements featuring ultra-thin models or control images. Women who reported high levels of body appreciation did not report negative media exposure effects. Furthermore, the protective role of body appreciation was also evident among women known to be vulnerable to media exposure. Women high on thin-ideal internalization and low on body appreciation reported appearance-discrepancies that were more salient and larger when they viewed models compared to the control group. However, women high on thin-ideal internalization and also high on body appreciation rated appearance-discrepancies as less important and no difference in size than the control group. The results support the notion that positive body image protects women from negative environmental appearance messages and suggests that promoting positive body image may be an effective intervention strategy. Copyright © 2013 Elsevier Ltd. All rights reserved.
Code of Federal Regulations, 2013 CFR
2013-07-01
... or approve necessary security regulations and orders for the protection of property and places under their jurisdiction/administration. Regulations and orders for the protection of property and personnel... protection of property and personnel of primary level field activities (PLFAs) headed by civilians, and...
Code of Federal Regulations, 2012 CFR
2012-07-01
... or approve necessary security regulations and orders for the protection of property and places under their jurisdiction/administration. Regulations and orders for the protection of property and personnel... protection of property and personnel of primary level field activities (PLFAs) headed by civilians, and...
Code of Federal Regulations, 2010 CFR
2010-07-01
... or approve necessary security regulations and orders for the protection of property and places under their jurisdiction/administration. Regulations and orders for the protection of property and personnel... protection of property and personnel of primary level field activities (PLFAs) headed by civilians, and...
Code of Federal Regulations, 2011 CFR
2011-07-01
... or approve necessary security regulations and orders for the protection of property and places under their jurisdiction/administration. Regulations and orders for the protection of property and personnel... protection of property and personnel of primary level field activities (PLFAs) headed by civilians, and...
Code of Federal Regulations, 2014 CFR
2014-07-01
... or approve necessary security regulations and orders for the protection of property and places under their jurisdiction/administration. Regulations and orders for the protection of property and personnel... protection of property and personnel of primary level field activities (PLFAs) headed by civilians, and...
29 CFR 1918.103 - Head protection.
Code of Federal Regulations, 2013 CFR
2013-07-01
... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Personal Protective Equipment § 1918.103 Head... National Standards Institute (ANSI) Z89.1-2009, “American National Standard for Industrial Head Protection...
29 CFR 1918.103 - Head protection.
Code of Federal Regulations, 2012 CFR
2012-07-01
... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Personal Protective Equipment § 1918.103 Head...-2003, “American National Standard for Industrial Head Protection,” which is incorporated by reference...
29 CFR 1926.100 - Head protection.
Code of Federal Regulations, 2011 CFR
2011-07-01
... Institute, Z89.1-1969, Safety Requirements for Industrial Head Protection. (c) Helmets for the head... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Personal Protective and Life Saving Equipment...
29 CFR 1918.103 - Head protection.
Code of Federal Regulations, 2014 CFR
2014-07-01
... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Personal Protective Equipment § 1918.103 Head... National Standards Institute (ANSI) Z89.1-2009, “American National Standard for Industrial Head Protection...
40 CFR 141.60 - Effective dates.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Effective dates. 141.60 Section 141.60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS National Primary Drinking Water Regulations: Maximum Contaminant Levels...
Ma, Michelle W.; Medicherla, Ratna C.; Qian, Meng; de Miera, Eleazar Vega-Saenz; Friedman, Erica B.; Berman, Russell S.; Shapiro, Richard L.; Pavlick, Anna C.; Ott, Patrick A.; Bhardwaj, Nina; Shao, Yongzhao; Osman, Iman; Darvishian, Farbod
2013-01-01
The sentinel lymph node is the initial site of metastasis. Down-regulation of anti-tumor immunity plays a role in nodal progression. Our objective was to investigate the relationship between immune modulation and sentinel lymph node positivity, correlating it with outcome in melanoma patients. Lymph node/primary tissues from melanoma patients prospectively accrued and followed at New York University Medical Center were evaluated for the presence of regulatory T-cells (Foxp3+) and dendritic cells (conventional: CD11c+, mature: CD86+) using immunohistochemistry. Primary melanoma immune cell profiles from sentinel lymph node-positive/-negative patients were compared. Logistic regression models inclusive of standard-of-care/immunologic primary tumor characteristics were constructed to predict the risk of sentinel lymph node positivity. Immunological responses in the positive sentinel lymph node were also compared to those in the negative non-sentinel node from the same nodal basin and matched negative sentinel lymph node. Decreased immune response was defined as increased regulatory T-cells or decreased dendritic cells. Associations between the expression of these immune modulators, clinicopathologic variables, and clinical outcome were evaluated using univariate/multivariate analyses. Primary tumor conventional dendritic cells and regression were protective against sentinel lymph node metastasis (odds ratio=0.714, 0.067; P=0.0099, 0.0816, respectively). Anti-tumor immunity was down-regulated in the positive sentinel lymph node with an increase in regulatory T-cells compared to the negative non-sentinel node from the same nodal basin (P=0.0005) and matched negative sentinel lymph node (P=0.0002). The positive sentinel lymph node also had decreased numbers of conventional dendritic cells compared to the negative sentinel lymph node (P<0.0001). Adding sentinel lymph node regulatory T-cell expression improved the discriminative power of a recurrence risk assessment model using clinical stage. Primary tumor regression was associated with prolonged disease-free (P=0.025) and melanoma-specific (P=0.014) survival. Our results support an assessment of local immune profiles in both the primary tumor and sentinel lymph node to help guide therapeutic decisions. PMID:22425909
Trotter welfare’s protection: A legislative perspective
Passantino, Annamaria; Giannetto, Claudia; Passantino, Letizia; Piccione, Giuseppe
2015-01-01
The Council of Europe’s activities in the field of animal welfare are particularly noteworthy and comprise the elaboration of several norms for the protection of animals. Concerning the specific European Directive, Regulations or Convention for the protection of animals, the Authors underline the missing of specifics recommendations concerning the welfare of sport horses and especially of trotters. Guidelines are reported by regulation of equestrian sports. The paper’s purpose is to give practical elements to individuate the welfare state and to promote a clear regulation on welfare, care and protection of trotters. PMID:27047109
7 CFR 301.38-4 - Interstate movement of regulated articles.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 5 2012-01-01 2012-01-01 false Interstate movement of regulated articles. 301.38-4...-4 Interstate movement of regulated articles. (a) Non-protected areas. Interstate movement of regulated articles into or through any State or area that is not designated as a protected area under § 301...
7 CFR 301.38-4 - Interstate movement of regulated articles.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 5 2011-01-01 2011-01-01 false Interstate movement of regulated articles. 301.38-4...-4 Interstate movement of regulated articles. (a) Non-protected areas. Interstate movement of regulated articles into or through any State or area that is not designated as a protected area under § 301...
Code of Federal Regulations, 2010 CFR
2010-10-01
... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Environmental Protection... Regulations System ENVIRONMENTAL PROTECTION AGENCY Ch. 15, App. I Appendix I to Chapter 15—Environmental Protection Agency; Class Justification for Other Than Full and Open Competition in Acquisitions From the...
Understanding Philip Morris's pursuit of US government regulation of tobacco
McDaniel, P; Malone, R
2005-01-01
Objective: To investigate Philip Morris's support of US Food and Drug Administration (FDA) regulation of tobacco products and analyse its relationship to the company's image enhancement strategies. Data sources: Internal Philip Morris documents released as part of the Master Settlement Agreement. Methods: Searches of the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) beginning with such terms as "FDA" and "regulatory strategy" and expanding to include relevant new terms. Results: Philip Morris's support for government regulation of tobacco is part of a broader effort to address its negative public image, which has a damaging impact on the company's stock price, political influence, and employee morale. Through regulation, the company seeks to enhance its legitimacy, redefine itself as socially responsible, and alter the litigation environment. Whereas health advocates frame tobacco use as a public health policy issue, Philip Morris's regulatory efforts focus on framing tobacco use as an individual choice by informed adults to use a risky product. This framing allows Philip Morris to portray itself as a reasonable and responsible manufacturer and marketer of risky products. Conclusions: Philip Morris's ability to improve its image through support of FDA regulation may undermine tobacco control efforts aimed at delegitimising the tobacco industry. It may also create the impression that Philip Morris's products are being made safer and ultimately protect the company from litigation. While strong regulation of tobacco products and promotion remain critical public health goals, previous experiences with tobacco regulation show that caution may be warranted. PMID:15923470
Understanding Philip Morris's pursuit of US government regulation of tobacco.
McDaniel, P A; Malone, R E
2005-06-01
To investigate Philip Morris's support of US Food and Drug Administration (FDA) regulation of tobacco products and analyse its relationship to the company's image enhancement strategies. Internal Philip Morris documents released as part of the Master Settlement Agreement. Searches of the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) beginning with such terms as "FDA" and "regulatory strategy" and expanding to include relevant new terms. Philip Morris's support for government regulation of tobacco is part of a broader effort to address its negative public image, which has a damaging impact on the company's stock price, political influence, and employee morale. Through regulation, the company seeks to enhance its legitimacy, redefine itself as socially responsible, and alter the litigation environment. Whereas health advocates frame tobacco use as a public health policy issue, Philip Morris's regulatory efforts focus on framing tobacco use as an individual choice by informed adults to use a risky product. This framing allows Philip Morris to portray itself as a reasonable and responsible manufacturer and marketer of risky products. Philip Morris's ability to improve its image through support of FDA regulation may undermine tobacco control efforts aimed at delegitimising the tobacco industry. It may also create the impression that Philip Morris's products are being made safer and ultimately protect the company from litigation. While strong regulation of tobacco products and promotion remain critical public health goals, previous experiences with tobacco regulation show that caution may be warranted.
48 CFR 970.0309 - Whistleblower Protection of Contractor Employees.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Whistleblower Protection of Contractor Employees. 970.0309 Section 970.0309 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY SUPPLEMENTARY REGULATIONS DOE MANAGEMENT AND OPERATING CONTRACTS Improper Business...
48 CFR 970.0309 - Whistleblower Protection of Contractor Employees.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Whistleblower Protection of Contractor Employees. 970.0309 Section 970.0309 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY SUPPLEMENTARY REGULATIONS DOE MANAGEMENT AND OPERATING CONTRACTS Improper Business...
40 CFR 52.2633 - Stack height regulations.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Stack height regulations. 52.2633 Section 52.2633 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... with the “Guideline for Determination of Good Engineering Practice Stack Height (Technical Support...
García Amez, Javier
2006-01-01
The genetic data is Spain is not regulated specifically, rather, we must look at the regulation on the protection of data of a personal nature. This is turn, establishes a series of general principles to apply to any type of data. Analysing this with other regulations that are dispersed both in the national and international regulations, we can deduce the rights and obligations in this field. This highlights the fact that one can't dispose of the genetic data in the same manner as the personal data.
Mikolajczak, Moïra; Petrides, K V; Hurry, Jane
2009-06-01
The present study seeks to extend the understanding of the role of dispositional factors in the aetiology of self-harm among adolescents. We hypothesized that higher trait emotional intelligence (trait EI) would be associated with a lower likelihood to harm oneself, and that this relationship would be mediated by the choice of coping strategies. Trait EI, coping styles and self-harm behaviours were assessed in 490 adolescents recruited from eight British schools. The results supported our hypothesis and showed that the relationship between trait EI and self-harm was partly mediated by the choice of coping strategies. Emotional coping was a particularly powerful mediator, suggesting that self-harm may be a way to decrease the negative emotions that are exacerbated by maladaptive emotional coping strategies, such as rumination, self-blame, and helplessness. Trait EI was correlated positively with adaptive coping styles and negatively with maladaptive coping styles, and depression. These findings emphasize the potential value of incorporating coping coaching programmes in the treatment of self-harm patients.
Hooker, Christine I.; Miyakawa, Asako; Verosky, Sara; Luerssen, Anna; Ayduk, Özlem N.
2012-01-01
Individuals with low self-esteem have been found to react more negatively to signs of interpersonal rejection than those with high self-esteem. However, previous research has found that individual differences in attentional control can attenuate negative reactions to social rejection among vulnerable, low self-esteem individuals. The current fMRI study sought to elucidate the neurobiological substrate of this buffering effect. We hypothesized and found that while looking at scenes of social rejection (vs negative scenes) low self-esteem high attentional control individuals engaged the rostral anterior cingulate cortex (rACC), an area of the brain associated with emotional control, more than their low self-esteem low attentional control peers. Furthermore, we found that low self-esteem high attentional control individuals evaluated social rejection as less arousing and less rejecting in a separate behavioral task. Importantly, activation in the rACC fully mediated the relationship between the interaction of self-esteem and attentional control and emotional evaluations, suggesting that the rACC activation underlies the buffering effects of attentional control. Results are discussed in terms of individual differences in emotional vulnerability and protection and by highlighting the role of rACC in emotion regulation. PMID:21609969
Perry, Nicole B; Calkins, Susan D; Nelson, Jackie A; Leerkes, Esther M; Marcovitch, Stuart
2012-07-01
The current study examined the moderating effect of children's cardiac vagal suppression on the association between maternal socialization of negative emotions (supportive and nonsupportive responses) and children's emotion regulation behaviors. One hundred and ninety-seven 4-year-olds and their mothers participated. Mothers reported on their reactions to children's negative emotions and children's regulatory behaviors. Observed distraction, an adaptive self-regulatory strategy, and vagal suppression were assessed during a laboratory task designed to elicit frustration. Results indicated that children's vagal suppression moderated the association between mothers' nonsupportive emotion socialization and children's emotion regulation behaviors such that nonsupportive reactions to negative emotions predicted lower observed distraction and lower reported emotion regulation behaviors when children displayed lower levels of vagal suppression. No interaction was found between supportive maternal emotion socialization and vagal suppression for children's emotion regulation behaviors. Results suggest physiological regulation may serve as a buffer against nonsupportive emotion socialization. Copyright © 2011 Wiley Periodicals, Inc.
Self-Compassion and the Self-Regulation of Exercise: Reactions to Recalled Exercise Setbacks.
Semenchuk, Brittany N; Strachan, Shaelyn M; Fortier, Michelle
2018-02-01
Self-compassion facilitates health behavior self-regulation; few studies have examined self-compassion and exercise. This online, cross-sectional study investigated self-compassion's relationship with exercise self-regulation of an exercise setback. Adults (N = 105) who had experienced an exercise setback within the last 6 months completed baseline measures, recalled an exercise setback, and completed questionnaires assessing self-regulation in this context. Self-compassion associated with self-determined motivations and exercise goal reengagement, and negatively related to extrinsic motivations, state rumination, and negative affect. Self-compassion predicted unique variance, beyond self-esteem, in exercise goal reengagement, external regulation, state rumination, and negative affect experienced after an exercise setback. Self-compassion and self-esteem had unique relationships with goal reengagement, state rumination, and situational motivation, while having a complementary relationship with negative affect. This research adds to the few studies that examine the role of self-compassion in exercise self-regulation by examining how self-compassion and self-esteem relate to reactions to a recalled exercise setback.
Perry, Nicole B.; Calkins, Susan D.; Nelson, Jackie A.; Leerkes, Esther M.; Marcovitch, Stuart
2011-01-01
The current study examined the moderating effect of children’s cardiac vagal suppression on the association between maternal socialization of negative emotions (supportive and non-supportive responses) and children’s emotion regulation behaviors. One hundred and ninety-seven 4-year-olds and their mothers participated. Mothers reported on their reactions to children’s negative emotions and children’s regulatory behaviors. Observed distraction, an adaptive self-regulatory strategy, and vagal suppression were assessed during a laboratory task designed to elicit frustration. Results indicated that children’s vagal suppression moderated the association between mothers’ non-supportive emotion socialization and children’s emotion regulation behaviors such that non-supportive reactions to negative emotions predicted lower observed distraction and lower reported emotion regulation behaviors when children displayed lower levels of vagal suppression. No interaction was found between supportive maternal emotion socialization and vagal suppression for children’s emotion regulation behaviors. Results suggest physiological regulation may serve as a buffer against non-supportive emotion socialization. PMID:22072217
Inhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CYLD
Komatsu, Kensei; Lee, Ji-Yun; Miyata, Masanori; Hyang Lim, Jae; Jono, Hirofumi; Koga, Tomoaki; Xu, Haidong; Yan, Chen; Kai, Hirofumi; Li, Jian-Dong
2013-01-01
The deubiquitinase CYLD acts as a key negative regulator to tightly control overactive inflammation. Most anti-inflammatory strategies have focused on directly targeting the positive regulator, which often results in significant side effects such as suppression of the host defence response. Here, we show that inhibition of phosphodiesterase 4B (PDE4B) markedly enhances upregulation of CYLD expression in response to bacteria, thereby suggesting that PDE4B acts as a negative regulator for CYLD. Interestingly, in Cyld-deficient mice, inhibition of PDE4B no longer suppresses inflammation. Moreover, PDE4B negatively regulates CYLD via specific activation of JNK2 but not JNK1. Importantly, ototopical post-inoculation administration of a PDE4 inhibitor suppresses inflammation in this animal model, thus demonstrating the therapeutic potential of targeting PDE4. These studies provide insights into how inflammation is tightly regulated via the inhibition of its negative regulator and may also lead to the development of new anti-inflammatory therapeutics that upregulate CYLD expression. PMID:23575688
Bromberg, Maggie H.; Anthony, Kelly K.; Gil, Karen M.; Franks, Lindsey; Schanberg, Laura E.
2012-01-01
Objectives This study utilized e-diaries to evaluate whether components of emotion regulation predict daily pain and function in children with juvenile idiopathic arthritis (JIA). Methods 43 children ages 8–17 years and their caregivers provided baseline reports of child emotion regulation. Children then completed thrice daily e-diary assessments of emotion, pain, and activity involvement for 28 days. E-diary ratings of negative and positive emotions were used to calculate emotion variability and to infer adaptive emotion modulation following periods of high or low emotion intensity. Hierarchical linear models were used to evaluate how emotion regulation related to pain and function. Results The attenuation of negative emotion following a period of high negative emotion predicted reduced pain; greater variability of negative emotion predicted higher pain and increased activity limitation. Indices of positive emotion regulation also significantly predicted pain. Conclusions Components of emotion regulation as captured by e-diaries predict important health outcomes in children with JIA. PMID:22037006
Thimgan, Matthew S; Suzuki, Yasuko; Seugnet, Laurent; Gottschalk, Laura; Shaw, Paul J
2010-08-31
Extended periods of waking result in physiological impairments in humans, rats, and flies. Sleep homeostasis, the increase in sleep observed following sleep loss, is believed to counter the negative effects of prolonged waking by restoring vital biological processes that are degraded during sleep deprivation. Sleep homeostasis, as with other behaviors, is influenced by both genes and environment. We report here that during periods of starvation, flies remain spontaneously awake but, in contrast to sleep deprivation, do not accrue any of the negative consequences of prolonged waking. Specifically, the homeostatic response and learning impairments that are a characteristic of sleep loss are not observed following prolonged waking induced by starvation. Recently, two genes, brummer (bmm) and Lipid storage droplet 2 (Lsd2), have been shown to modulate the response to starvation. bmm mutants have excess fat and are resistant to starvation, whereas Lsd2 mutants are lean and sensitive to starvation. Thus, we hypothesized that bmm and Lsd2 may play a role in sleep regulation. Indeed, bmm mutant flies display a large homeostatic response following sleep deprivation. In contrast, Lsd2 mutant flies, which phenocopy aspects of starvation as measured by low triglyceride stores, do not exhibit a homeostatic response following sleep loss. Importantly, Lsd2 mutant flies are not learning impaired after sleep deprivation. These results provide the first genetic evidence, to our knowledge, that lipid metabolism plays an important role in regulating the homeostatic response and can protect against neuronal impairments induced by prolonged waking.
Attention regulates anger and fear to predict changes in adolescent risk-taking behaviors
Kim-Spoon, Jungmeen; Holmes, Christopher; Deater-Deckard, Kirby
2014-01-01
Background Regulation of negative affect is critical to healthy development in childhood and adolescence. We conducted a longitudinal study examining the moderating role of attention control in the effects of anger and fear on changes in risk-taking behaviors from early to middle adolescence. Method The sample involved participants from the Study of Early Child Care and Youth Development (SECCYD), assessed at 9, 11, and 15 years of age. Composite scores for anger, fear, and attention control were computed using indicators from multiple informants, and risk-taking behaviors were assessed based on adolescents’ self-reports. Results Latent difference score analysis indicated significant moderating effects of attention control showing that increased anger between 9 and 11 years was related to increases in risk-taking behaviors between 11 and 15 years only for adolescents with low attention control but not for adolescents with high attention control. In contrast, significant moderating effects of attention control for the link between fear and risk-taking behaviors suggested increased fear between 9 and 11 years tended to be associated with decreases in risk-taking behaviors between 11 and 15 years only for adolescents with high attention control but not for adolescents with low attention control. Conclusions Attention control regulates the connections between negative affect such as anger and fear with changes in adolescent risk-taking behaviors. Our data suggest the protective role of strong attention control against the development of risk-taking behaviors in adolescence as it demotes the effects of anger and promotes the effects of fear. PMID:25280179
Mazza, Monica; Pino, Maria Chiara; Tempesta, Daniela; Catalucci, Alessia; Masciocchi, Carlo; Ferrara, Michele
2016-01-01
Post-Traumatic Stress Disorder (PTSD) is a chronic anxiety disorder. The continued efforts to control the distressing memories by traumatized individuals, together with the reduction of responsiveness to the outside world, are called Emotional Numbing (EN). The EN is one of the central symptoms in PTSD and it plays an integral role not only in the development and maintenance of post-traumatic symptomatology, but also in the disability of emotional regulation. This disorder shows an abnormal response of cortical and limbic regions which are normally involved in understanding emotions since the very earliest stages of the development of processing ability. Patients with PTSD exhibit exaggerated brain responses to emotionally negative stimuli. Identifying the neural correlates of emotion regulation in these subjects is important for elucidating the neural circuitry involved in emotional and empathic dysfunction. We showed that PTSD patients, all survivors of the L'Aquila 2009 earthquake, have a higher sensitivity to negative emotion and lower empathy levels. These emotional and empathic deficits are accompanied by neural brain functional correlates. Indeed PTSD subjects exhibit functional abnormalities in brain regions that are involved in stress regulation and emotional responses. The reduced activation of the frontal areas and a stronger activation of the limbic areas when responding to emotional stimuli could lead the subjects to enact coping strategies aimed at protecting themselves from the re-experience of pain related to traumatic events. This would result in a dysfunctional hyperactivation of subcortical areas, which may cause emotional distress and, consequently, impaired social relationships often reported by PTSD patients.
Christou-Champi, Spyros; Farrow, Tom F D; Webb, Thomas L
2015-01-01
Emotion regulation (ER) is vital to everyday functioning. However, the effortful nature of many forms of ER may lead to regulation being inefficient and potentially ineffective. The present research examined whether structured practice could increase the efficiency of ER. During three training sessions, comprising a total of 150 training trials, participants were presented with negatively valenced images and asked either to "attend" (control condition) or "reappraise" (ER condition). A further group of participants did not participate in training but only completed follow-up measures. Practice increased the efficiency of ER as indexed by decreased time required to regulate emotions and increased heart rate variability (HRV). Furthermore, participants in the ER condition spontaneously regulated their negative emotions two weeks later and reported being more habitual in their use of ER. These findings indicate that structured practice can facilitate the automatic control of negative emotions and that these effects persist beyond training.
Davis, Elizabeth L; Levine, Linda J; Lench, Heather C; Quas, Jodi A
2010-08-01
Metacognitive emotion regulation strategies involve deliberately changing thoughts or goals to alleviate negative emotions. Adults commonly engage in this type of emotion regulation, but little is known about the developmental roots of this ability. Two studies were designed to assess whether 5- and 6-year-old children can generate such strategies and, if so, the types of metacognitive strategies they use. In Study 1, children described how story protagonists could alleviate negative emotions. In Study 2, children recalled times that they personally had felt sad, angry, and scared and described how they had regulated their emotions. In contrast to research suggesting that young children cannot use metacognitive regulation strategies, the majority of children in both studies described such strategies. Children were surprisingly sophisticated in their suggestions for how to cope with negative emotions and tailored their regulatory responses to specific emotional situations. Copyright 2010 APA
Davis, Elizabeth L.; Levine, Linda J.; Lench, Heather C.; Quas, Jodi A.
2010-01-01
Metacognitive emotion regulation strategies involve deliberately changing thoughts or goals to alleviate negative emotions. Adults commonly engage in this type of emotion regulation, but little is known about the developmental roots of this ability. Two studies were designed to assess whether 5- and 6-year-old children can generate such strategies and, if so, the types of metacognitive strategies they employ. In Study 1, children described how story protagonists could alleviate negative emotions. In Study 2, children recalled times that they personally had felt sad, angry, and scared, and described how they had regulated their emotions. In contrast to research suggesting that young children cannot use metacognitive regulation strategies, the majority of children in both studies described such strategies. Children were surprisingly sophisticated in their suggestions for how to cope with negative emotions and tailored their regulatory responses to specific emotional situations. PMID:20677867
Sagui, Sara J; Levens, Sara M
2016-10-01
Stress contributes to poor health outcomes; importantly, a stress reaction begins with the negative appraisal of a situation. The ability to use cognitive reappraisal, an emotion regulation strategy that involves reinterpreting an initial appraisal to change its emotional impact, could be a protective factor against the health consequences of stress reactivity. The present study investigated (a) if cognitive reappraisal ability (CRA) acts as a stress buffer against a body mass index (BMI) indicative of being overweight (≥25 kg/m2) or obese (≥30 kg/m2), and (b) if this buffering effect persists against the indirect influences of perceived stress reactivity (PSR) on Type 2 diabetes. One hundred fifty participants (54% female; mean age = 40.4 years ± 12.4 years) completed an online CRA task, self-report measures of PSR, height, weight, and Type 2 diabetes diagnosis on Amazon's Mechanical Turk. Results revealed that CRA significantly interacted with PSR to predict BMI, which indirectly predicted Type 2 diabetes. Individuals with higher PSR and higher CRA exhibited BMIs within a normal weight range and lower incidence of Type 2 diabetes. In contrast, individuals with higher PSR and lower CRA were overweight or obese, with a higher incidence of Type 2 diabetes. Interestingly, higher CRA was not protective in those who had lower levels of PSR. Findings from this study suggest that emotion regulation interventions can be developed to indirectly target Type 2 diabetes and similar obesity-related illnesses, and that emotion regulation interventions should be tailored to the individual. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
MicroRNA-132 protects hippocampal neurons against oxygen-glucose deprivation-induced apoptosis.
Sun, Zu-Zhen; Lv, Zhan-Yun; Tian, Wen-Jing; Yang, Yan
2017-09-01
Hypoxic-ischemic brain injury (HIBI) results in death or long-term neurologic impairment in both adults and children. In this study, we investigated the effects of microRNA-132 (miR-132) dysregulation on oxygen-glucose deprivation (OGD)-induced apoptosis in fetal rat hippocampal neurons, in order to reveal the therapeutic potential of miR-132 on HIBI. MiR-132 dysregulation was induced prior to OGD exposure by transfection of primary fetal rat hippocampal neurons with miR-132 mimic or miR-132 inhibitor. The effects of miR-132 overexpression and suppression on OGD-stimulated hippocampal neurons were evaluated by detection of cell viability, apoptotic cells rate, and the expression of apoptosis-related proteins. Besides, TargetScan database and dual luciferase activity assay were used to seek a target gene of miR-132. As a result, miR-132 was highly expressed in hippocampal neurons following 2 h of OGD exposure. MiR-132 overexpression significantly increased OGD-diminished cell viability and reduced OGD-induced apoptosis at 12, 24, and 48 h post-OGD. MiR-132 overexpression significantly down-regulated the expressions of Bax, cytochrome c, and caspase-9, but up-regulated BCl-2. Caspase-3 activity was also significantly decreased by miR-132 overexpression. Furthermore, FOXO3 was a direct target of miR-132, and it was negatively regulated by miR-132. To conclude, our results provide evidence that miR-132 protects hippocampal neurons against OGD injury by inhibiting apoptosis.
Ren, Jie; Zhang, Nan; Liao, Haihan; Chen, Si; Xu, Ling; Li, Jing; Yang, Zheng; Deng, Wei; Tang, Qizhu
2017-07-15
To explore the effects of caffeic acid phenethyl ester (CAPE) on cardiac hypertrophy induced by pressure overload. Male wild-type C57 mice, aged 8-10weeks, were used for aortic banding (AB) to induce cardiac hypertrophy. CAPE or (resveratrol) RS was administered from the 3rd day after AB surgery for 6weeks. Echocardiography and hemodynamic analysis were performed to estimate cardiac function. Mice hearts were collected for H&E and PSR staining. Western blot analysis and quantitative PCR were performed for to investigate molecular mechanism. We further confirmed our findings in H9c2 cardiac fibroblasts treated with PE or CAPE. CAPE protected against cardiac hypertrophy induced by pressure overload, as evidenced by inhibition of cardiac hypertrophy and improvement in mouse cardiac function. The effect of CAPE on cardiac hypertrophy was mediated via inhibition of the MEK/ERK and TGFβ-Smad signaling pathways. We also demonstrated that CAPE protected H9c2 cells from PE-induced hypertrophy in vitro via a similar molecular mechanism as seen in the mouse heart. Finally, CAPE seemed to be as effective as RS for treatment of pressure overload induced mouse cardiac hypertrophy. Our results suggest that CAPE may play an important role in the regulation of cardiac hypertrophy induced by pressure overload via negative regulation of the MEK/ERK and TGFβ/Smad signaling pathways. These results indicate that CAPE could potentially be used for treatment of cardiac hypertrophy. Copyright © 2017 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Thorslund, Josefin; Jarsjö, Jerker; Destouni, Georgia
2017-04-01
Wetlands are often considered as nature-based solutions that can provide a multitude of services of great social, economic and environmental value to humankind. The services may include recreation, greenhouse gas sequestration, contaminant retention, coastal protection, groundwater level and soil moisture regulation, flood regulation and biodiversity support. Changes in land-use, water use and climate can all impact wetland functions and occur at scales extending well beyond the local scale of an individual wetland. However, in practical applications, management decisions usually regard and focus on individual wetland sites and local conditions. To understand the potential usefulness and services of wetlands as larger-scale nature-based solutions, e.g. for mitigating negative impacts from large-scale change pressures, one needs to understand the combined function multiple wetlands at the relevant large scales. We here systematically investigate if and to what extent research so far has addressed the large-scale dynamics of landscape systems with multiple wetlands, which are likely to be relevant for understanding impacts of regional to global change. Our investigation regards key changes and impacts of relevance for nature-based solutions, such as large-scale nutrient and pollution retention, flow regulation and coastal protection. Although such large-scale knowledge is still limited, evidence suggests that the aggregated functions and effects of multiple wetlands in the landscape can differ considerably from those observed at individual wetlands. Such scale differences may have important implications for wetland function-effect predictability and management under large-scale change pressures and impacts, such as those of climate change.
The creation of the Chagos marine protected area: a fisheries perspective(☆).
Dunne, Richard P; Polunin, Nicholas V C; Sand, Peter H; Johnson, Magnus L
2014-01-01
From a fisheries perspective, the declaration of a 640,000 km² "no-take" Marine Protected Area (MPA) in the Chagos Archipelago in 2010 was preceded by inadequate consideration of the scientific rationale for protection. The entire area was already a highly regulated zone which had been subject to a well-managed fisheries licensing system. The island of Diego Garcia, the only area where there is evidence of overfishing has, because of its military base, been excluded from the MPA. The no-take mandate removes the primary source of sustenance and economic sustainability of any inhabitants, thus effectively preventing the return of the original residents who were removed for political reasons in the 1960s and 1970s. The principles of natural resource conservation and use have been further distorted by forcing offshore fishing effort to other less well-managed areas where it will have a greater negative impact on the well-being of the species that were claimed to be one of the primary beneficiaries of the declaration. A failure to engage stakeholders has resulted in challenges in both the English courts and before an international tribunal.
γδ T Cells Support Pancreatic Oncogenesis by Restraining αβ T Cell Activation.
Daley, Donnele; Zambirinis, Constantinos Pantelis; Seifert, Lena; Akkad, Neha; Mohan, Navyatha; Werba, Gregor; Barilla, Rocky; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu Raj Kumar; Avanzi, Antonina; Tippens, Daniel; Narayanan, Rajkishen; Jang, Jung-Eun; Newman, Elliot; Pillarisetty, Venu Gopal; Dustin, Michael Loran; Bar-Sagi, Dafna; Hajdu, Cristina; Miller, George
2016-09-08
Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated γδT cell population, which constituted ∼40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of γδT cells was contingent on diverse chemokine signals. Deletion, depletion, or blockade of γδT cell recruitment was protective against PDA and resulted in increased infiltration, activation, and Th1 polarization of αβT cells. Although αβT cells were dispensable to outcome in PDA, they became indispensable mediators of tumor protection upon γδT cell ablation. PDA-infiltrating γδT cells expressed high levels of exhaustion ligands and thereby negated adaptive anti-tumor immunity. Blockade of PD-L1 in γδT cells enhanced CD4(+) and CD8(+) T cell infiltration and immunogenicity and induced tumor protection suggesting that γδT cells are critical sources of immune-suppressive checkpoint ligands in PDA. We describe γδT cells as central regulators of effector T cell activation in cancer via novel cross-talk. Copyright © 2016 Elsevier Inc. All rights reserved.
Does melanin matter in the dark?
Płonka, Przemysław M; Picardo, Mauro; Slominski, Andrzej T
2017-07-01
In living cells, melanin pigment is formed within melanosomes, which not only protect the cells from autodestruction, but also serve as second messenger organelles regulating important skin functions, with melanocytes acting as primary sensory and regulatory cells of the epidermis. Yet, one can argue that skin melanin, which may negatively affect cellular homeostasis in melanoma, really exerts protective functions. Consequently, the actual functions of melanin and the melanogenic pathway in skin biology remains enigmatic. Yet, the solution of this riddle seems simple - to check the actual influence of natural melanin on skin cells in the dark. Since many interesting hypotheses and theories put forward in this respect did not survive confrontation with the experiment, a leading pigment research group from Naples was brave to "jump off the cliff" by confronting theory with experimental reality. They showed that, in the dark, human hair-derived melanin promotes inflammatory responses in keratinocytes, lowers their viability, promotes oxidative stress, and that pheomelanin does so more strongly than eumelanin. Thus, pheomelanin hardly protects red-haired individuals, even when avoiding the sun. Black hairs do not do much better either, unless they undergo graying. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
It Takes a Village: Protecting Rural African American Youth in the Context of Racism
ERIC Educational Resources Information Center
Berkel, Cady; Murry, Velma McBride; Hurt, Tera R.; Chen, Yi-fu; Brody, Gene H.; Simons, Ronald L.; Cutrona, Carolyn; Gibbons, Frederick X.
2009-01-01
Prior research demonstrates negative consequences of racism, however, little is known about community, parenting, and intrapersonal mechanisms that protect youth. Using a mixed-methods approach, this study illuminated linkages between positive and negative contextual influences on rural African American adolescent outcomes. Quantitative results…
Federal Register 2010, 2011, 2012, 2013, 2014
2013-12-03
... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 62 [EPA-R05-OAR-2013-0678; FRL-9903-33-Region-5] Direct Final Approval of Hospital/Medical/Infectious Waste Incinerator Negative Declaration for Designated Facilities and Pollutants: Michigan and Wisconsin AGENCY: Environmental Protection Agency (EPA...
40 CFR 62.7853 - Identification of plan-negative declaration.
Code of Federal Regulations, 2012 CFR
2012-07-01
... chapter. (b) Letters from the City of Albuquerque Air Pollution Control Division dated July 8, 1980, and... declaration. 62.7853 Section 62.7853 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Mexico Total Reduced Sulfur Emissions from Kraft Pulp Mills § 62.7853 Identification of plan—negative...
40 CFR 62.7853 - Identification of plan-negative declaration.
Code of Federal Regulations, 2014 CFR
2014-07-01
... chapter. (b) Letters from the City of Albuquerque Air Pollution Control Division dated July 8, 1980, and... declaration. 62.7853 Section 62.7853 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Mexico Total Reduced Sulfur Emissions from Kraft Pulp Mills § 62.7853 Identification of plan—negative...
40 CFR 62.7853 - Identification of plan-negative declaration.
Code of Federal Regulations, 2013 CFR
2013-07-01
... chapter. (b) Letters from the City of Albuquerque Air Pollution Control Division dated July 8, 1980, and... declaration. 62.7853 Section 62.7853 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Mexico Total Reduced Sulfur Emissions from Kraft Pulp Mills § 62.7853 Identification of plan—negative...
ERIC Educational Resources Information Center
Earnshaw, Valerie A.; Rosenthal, Lisa; Carroll-Scott, Amy; Peters, Susan M.; McCaslin, Catherine; Ickovics, Jeannette R.
2014-01-01
Experiencing bullying as a victim is associated with negative health and health behavior outcomes, including substance use, among adolescents. However, understandings of protective factors--factors that enhance adolescents' resilience to the negative consequences of bullying--remain limited. The current study investigates whether teacher…
Anxiety and the Use of Alcohol-Related Protective Behavioral Strategies
ERIC Educational Resources Information Center
Napper, Lucy E.; LaBrie, Joseph W.; Hummer, Justin F.
2015-01-01
Protective behavioral strategies (PBS) are useful skills for reducing the negative consequences of alcohol. The moderating effects of anxiety on the relationship between 3 different types of PBS and negative consequences were examined among students accessing college counseling services. Results revealed a significant interaction between anxiety…
Neural Correlates of Emotion Regulation in Patients with Schizophrenia and Non-Affected Siblings
van der Velde, Jorien; Pijnenborg, Gerdina; Wiersma, Durk; Bruggeman, Richard; Aleman, André
2014-01-01
Background Patients with schizophrenia often experience problems regulating their emotions. Non-affected relatives show similar difficulties, although to a lesser extent, and the neural basis of such difficulties remains to be elucidated. In the current paper we investigated whether schizophrenia patients, non-affected siblings and healthy controls (HC) exhibit differences in brain activation during emotion regulation. Methods All subjects (n = 20 per group) performed an emotion regulation task while they were in an fMRI scanner. The task contained two experimental conditions for the down-regulation of emotions (reappraise and suppress), in which IAPS pictures were used to generate a negative affect. We also assessed whether the groups differed in emotion regulation strategies used in daily life by means of the emotion regulation questionnaire (ERQ). Results Though the overall negative affect was higher for patients as well as for siblings compared to HC for all conditions, all groups reported decreased negative affect after both regulation conditions. Nonetheless, neuroimaging results showed hypoactivation relative to HC in VLPFC, insula, middle temporal gyrus, caudate and thalamus for patients when reappraising negative pictures. In siblings, the same pattern was evident as in patients, but only in cortical areas. Conclusions Given that all groups performed similarly on the emotion regulation task, but differed in overall negative affect ratings and brain activation, our findings suggest reduced levels of emotion regulation processing in neural circuits in patients with schizophrenia. Notably, this also holds for siblings, albeit to a lesser extent, indicating that it may be part and parcel of a vulnerability for psychosis. PMID:24941136
40 CFR 52.1678 - Control strategy and regulations: Particulate matter.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy and regulations: Particulate matter. 52.1678 Section 52.1678 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New York...
40 CFR 146.2 - Law authorizing these regulations.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Law authorizing these regulations. 146.2 Section 146.2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) UNDERGROUND INJECTION CONTROL PROGRAM: CRITERIA AND STANDARDS General Provisions § 146.2 Law...
40 CFR 146.2 - Law authorizing these regulations.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Law authorizing these regulations. 146.2 Section 146.2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) UNDERGROUND INJECTION CONTROL PROGRAM: CRITERIA AND STANDARDS General Provisions § 146.2 Law...
40 CFR 146.2 - Law authorizing these regulations.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Law authorizing these regulations. 146.2 Section 146.2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) UNDERGROUND INJECTION CONTROL PROGRAM: CRITERIA AND STANDARDS General Provisions § 146.2 Law...
78 FR 281 - Submission for OMB Review; Comment Request
Federal Register 2010, 2011, 2012, 2013, 2014
2013-01-03
...,331. Animal and Plant Health Inspection Service Title: Horse Protection Regulations. OMB Control Number: 0579-0056. Summary of Collection: 9 CFR Part 11, Regulations, implement the Horse Protection Act... 9 of the Act. The Horse Protection Legislation was enacted to prevent showing, exhibiting, selling...
Takaya, Akiko; Tabuchi, Fumiaki; Tsuchiya, Hiroko; Isogai, Emiko; Yamamoto, Tomoko
2008-06-01
Lon protease, a member of the ATP-dependent protease family, regulates numerous cellular systems by degrading specific substrates. Here, we demonstrate that Lon is involved in the regulation of quorum-sensing (QS) signaling systems in Pseudomonas aeruginosa, an opportunistic human pathogen. The organism has two acyl-homoserine lactone (HSL)-mediated QS systems, LasR/LasI and RhlR/RhlI. Many reports have demonstrated that these two systems are regulated and interconnected by global regulators. We found that lon-disrupted cells overproduce pyocyanin, the biosynthesis of which depends on the RhlR/RhlI system, and show increased levels of a transcriptional regulator, RhlR. The QS systems are organized hierarchically: the RhlR/RhlI system is subordinate to LasR/LasI. To elucidate the mechanism by which Lon negatively regulates RhlR/RhlI, we examined the effect of lon disruption on the LasR/LasI system. We found that Lon represses the expression of LasR/LasI by degrading LasI, an HSL synthase, leading to negative regulation of the RhlR/RhlI system. RhlR/RhlI was also shown to be regulated by Lon independently of LasR/LasI via regulation of RhlI, an HSL synthase. In view of these findings, it is suggested that Lon protease is a powerful negative regulator of both HSL-mediated QS systems in P. aeruginosa.
Butler, Emily A; Gross, James J; Barnard, Kobus
2014-04-01
In theory, the essence of emotion is coordination across experiential, behavioral, and physiological systems in the service of functional responding to environmental demands. However, people often regulate emotions, which could either reduce or enhance cross-system concordance. The present study tested the effects of two forms of emotion regulation (expressive suppression, positive reappraisal) on concordance of subjective experience (positive-negative valence), expressive behavior (positive and negative), and physiology (inter-beat interval, skin conductance, blood pressure) during conversations between unacquainted young women. As predicted, participants asked to suppress showed reduced concordance for both positive and negative emotions. Reappraisal instructions also reduced concordance for negative emotions, but increased concordance for positive ones. Both regulation strategies had contagious interpersonal effects on average levels of responding. Suppression reduced overall expression for both regulating and uninstructed partners, while reappraisal reduced negative experience. Neither strategy influenced the uninstructed partners' concordance. These results suggest that emotion regulation impacts concordance by altering the temporal coupling of phasic subsystem responses, rather than by having divergent effects on subsystem tonic levels. Copyright © 2013 Elsevier B.V. All rights reserved.
NASA Technical Reports Server (NTRS)
Klein, S. B.
1980-01-01
Although many states afford some measure of protection for wetland areas through flood-plain regulations or through programs for coastal areas, shorelands, scenic and wild rivers or pollution control, few states have programs that adequately deal with conservation of wetlands. Only 16 states have legislation specifically regulating development or use of wetlands. Most of the wetland acts apply only to coastal wetlands, several to inland wetlands and three acts apply to both. Many other states are still regulating wetland use through the dredge and fill and/or critical area program. Several offer tax incentives to property owners to encourage protection of wetlands or broader open spaces. Many states have acquired wetlands for park and wildlife purposes and a large measure of wetland protection is achieved by the very restrictive controls applied to floodways areas. Direct floodplain or floodway regulations or state standards for local regulations were adopted in 24 states but protection of ecological values of wetlands is rarely an explicit objective of these programs. Scenic and wild river programs adopted in one half of the states provide some protection for wetland areas.
Alexithymia and Mood: Recognition of Emotion in Self and Others.
Lyvers, Michael; Kohlsdorf, Susan M; Edwards, Mark S; Thorberg, Fred Arne
2017-01-01
The present study explored relationships between alexithymia-a trait characterized by difficulties identifying and describing feelings and an external thinking style-and negative moods, negative mood regulation expectancies, facial recognition of emotions, emotional empathy, and alcohol consumption. The sample consisted of 102 university (primarily psychology) students (13 men, 89 women) aged 18 to 50 years (M = 22.18 years). Participants completed the Toronto Alexithymia Scale (TAS-20), Negative Mood Regulation Scale (NMRS), Depression Anxiety Stress Scales (DASS-21), Reading the Mind in the Eyes Test (RMET), Interpersonal Reactivity Index (IRI), and Alcohol Use Disorders Identification Test (AUDIT). Results were consistent with previous findings of positive relationships of TAS-20 alexithymia scores with both alcohol use (AUDIT) and negative moods (DASS-21) and a negative relationship with emotional self-regulation as indexed by NMRS. Predicted negative associations of both overall TAS-20 alexithymia scores and the externally oriented thinking (EOT) subscale of the TAS-20 with both RMET facial recognition of emotions and the empathic concern (EC) subscale of the IRI were supported. The mood self-regulation index NMRS fully mediated the relationship between alexithymia and negative moods. Hierarchical linear regressions revealed that, after other relevant variables were controlled for, the EOT subscale of the TAS-20 predicted RMET and EC. The concrete thinking or EDT facet of alexithymia thus appears to be associated with diminished facial recognition of emotions and reduced emotional empathy. The negative moods associated with alexithymia appear to be linked to subjective difficulties in self-regulation of emotions.
You, Xuqun; Ju, Chengting; Wang, Mo; Zhang, Baoshan; Liu, Pei
2017-11-19
In this study, we hypothesized that there is an age difference in the influence of negative emotion on decision-making and that this age difference is related to emotion regulation strategies. We carried out two studies. In the first, the older and younger adults completed the ultimatum game (UG) while in either an induced negative emotional or a neutral context. In the second, both the older and younger adults completed the UG while in an induced negative emotion while using either emotion reappraisal or expressive suppression to regulate their emotions during the task. The first study showed that, unlike younger adults, the older adults made similar choices in the neutral and negative induction groups. In addition, the older adults predominantly used a reappraisal strategy in both the negative and neutral emotional states, whereas the younger adults predominantly used a suppression strategy in the negative emotional state. In the second study, after the emotion regulation strategies were experimentally manipulated so that both age groups used the same strategy, we found no age difference in decision-making. Our findings indicated that the influence of negative emotion on decision-making differs between older and younger adults and that this age difference was associated with their different emotion regulation processes. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
The Emotional Stroop as an Emotion Regulation Task.
Kappes, Cathleen; Bermeitinger, Christina
2016-01-01
The present studies investigate age differences observed when performing the emotional Stroop task considered as an expression of emotion regulation. Previous studies employing this task showed mixed findings regarding age differences, with a lack of evidence for positivity effects. However, moderating factors such as arousal or dispositional (emotion) regulation strategies were mostly not taken into account. Moreover, relations between Stroop effects and emotional reactions were not examined. In two studies (Study 1/2: nyoung = 26/41; nold = 19/39), an emotional Stroop task was employed and valence (negative, neutral, positive [Study 2 only]) and arousal of the word stimuli were varied. Additionally, flexible goal adjustment (FGA), positive and negative affect in the last 12 months, and change in momentary affect (Study 2 only) were measured. Study 1 showed larger emotional Stroop effects (ESE) in older than younger adults with medium arousing negative words. We also found correlations between FGA (positive correlation) as well as negative affect (negative correlation) and the ESE with medium arousing negative words. Study 2 corroborates these findings by exhibiting positive change in momentary affect with larger ESEs for medium arousing negative words in the older age group. The findings emphasize the importance of including arousal level and dispositional regulation measures (such as FGA) as moderating factors in age differences and within-group differences in emotion regulation. Although we did not find evidence for a positivity effect, processing in the emotional Stroop task was related to positive change in momentary affect and less negative affect in the older age group. Taken together, our experiments demonstrate that the emotional Stroop task is suited as a measure for emotion induction and related emotion regulation mechanisms.
Ji, Haofeng; Shen, Xiuda; Gao, Feng; Ke, Bibo; Freitas, Maria Cecilia S; Uchida, Yoichiro; Busuttil, Ronald W; Zhai, Yuan; Kupiec-Weglinski, Jerzy W
2010-10-01
Programmed death-1 (PD-1)/B7-H1 costimulation acts as a negative regulator of host alloimmune responses. Although CD4 T cells mediate innate immunity-dominated ischemia and reperfusion injury (IRI) in the liver, the underlying mechanisms remain to be elucidated. This study focused on the role of PD-1/B7-H1 negative signaling in liver IRI. We used an established mouse model of partial liver warm ischemia (90 minutes) followed by reperfusion (6 hours). Although disruption of PD-1 signaling after anti-B7-H1 monoclonal antibody treatment augmented hepatocellular damage, its stimulation following B7-H1 immunoglobulin (B7-H1Ig) fusion protected livers from IRI, as evidenced by low serum alanine aminotransferase levels and well-preserved liver architecture. The therapeutic potential of B7-H1 engagement was evident by diminished intrahepatic T lymphocyte, neutrophil, and macrophage infiltration/activation; reduced cell necrosis/apoptosis but enhanced anti-necrotic/apoptotic Bcl-2/Bcl-xl; and decreased proinflammatory chemokine/cytokine gene expression in parallel with selectively increased interleukin (IL)-10. Neutralization of IL-10 re-created liver IRI and rendered B7-H1Ig-treated hosts susceptible to IRI. These findings were confirmed in T cell-macrophage in vitro coculture in which B7-H1Ig diminished tumor necrosis factor-α/IL-6 levels in an IL-10-dependent manner. Our novel findings document the essential role of the PD-1/B7-H1 pathway in liver IRI. This study is the first to demonstrate that stimulating PD-1 signals ameliorated liver IRI by inhibiting T cell activation and Kupffer cell/macrophage function. Harnessing mechanisms of negative costimulation by PD-1 upon T cell-Kupffer cell cross-talk may be instrumental in the maintenance of hepatic homeostasis by minimizing organ damage and promoting IL-10-dependent cytoprotection.
40 CFR 503.4 - Relationship to other regulations.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Relationship to other regulations. 503.4 Section 503.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SEWAGE SLUDGE STANDARDS FOR THE USE OR DISPOSAL OF SEWAGE SLUDGE General Provisions § 503.4 Relationship to other...
40 CFR 503.4 - Relationship to other regulations.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Relationship to other regulations. 503.4 Section 503.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SEWAGE SLUDGE STANDARDS FOR THE USE OR DISPOSAL OF SEWAGE SLUDGE General Provisions § 503.4 Relationship to other...
40 CFR 52.1384 - Emission control regulations.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 40 Protection of Environment 4 2012-07-01 2012-07-01 false Emission control regulations. 52.1384 Section 52.1384 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Quality and Exxon Company, USA, adopted by Board Order issued on June 12, 1998, by the Montana Board of...
40 CFR 52.1384 - Emission control regulations.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Emission control regulations. 52.1384 Section 52.1384 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Quality and Exxon Company, USA, adopted by Board Order issued on June 12, 1998, by the Montana Board of...
40 CFR 52.1384 - Emission control regulations.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Emission control regulations. 52.1384 Section 52.1384 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Quality and Exxon Company, USA, adopted by Board Order issued on June 12, 1998, by the Montana Board of...
40 CFR 52.1384 - Emission control regulations.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Emission control regulations. 52.1384 Section 52.1384 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Quality and Exxon Company, USA, adopted by Board Order issued on June 12, 1998, by the Montana Board of...
Federal Register 2010, 2011, 2012, 2013, 2014
2011-03-22
... ENVIRONMENTAL PROTECTION AGENCY [FRL-9284-9] Cross-Media Electronic Reporting Regulation... (EPA). ACTION: Notice. SUMMARY: This notice announces EPA's approval, under regulations for Cross-Media..., [email protected] . SUPPLEMENTARY INFORMATION: On October 13, 2005, the final Cross-Media Electronic...
76 FR 81789 - Consumer Leasing (Regulation M); Correction
Federal Register 2010, 2011, 2012, 2013, 2014
2011-12-29
... BUREAU OF CONSUMER FINANCIAL PROTECTION 12 CFR Part 1013 [Docket No. CFPB-2011-0026] RIN 3170-AA06 Consumer Leasing (Regulation M); Correction AGENCY: Bureau of Consumer Financial Protection. ACTION...). The interim final rule established a new Regulation M (Consumer Leasing) in accordance with the...
Circuit protects regulated power supply against overload current
NASA Technical Reports Server (NTRS)
Airth, H. B.
1966-01-01
Sensing circuit in which a tunnel diode controls a series regulator transistor protects a low voltage transistorized dc regulator from damage by excessive load currents. When a fault occurs, the faulty circuit is limited to a preset percentage of the current when limiting first occurs.
Full Freedom of Expression for the Media.
ERIC Educational Resources Information Center
Packwood, Bob
1984-01-01
While print media are protected by the First Amendment, the electronic media are subject to content regulations. Gives an historical overview, showing how the Federal Communications Commission came to regulate radio. There should be a constitutional solution, an amendment protecting electronic media from government regulations. (CS)
Large-scale bioenergy production: how to resolve sustainability trade-offs?
NASA Astrophysics Data System (ADS)
Humpenöder, Florian; Popp, Alexander; Bodirsky, Benjamin Leon; Weindl, Isabelle; Biewald, Anne; Lotze-Campen, Hermann; Dietrich, Jan Philipp; Klein, David; Kreidenweis, Ulrich; Müller, Christoph; Rolinski, Susanne; Stevanovic, Miodrag
2018-02-01
Large-scale 2nd generation bioenergy deployment is a key element of 1.5 °C and 2 °C transformation pathways. However, large-scale bioenergy production might have negative sustainability implications and thus may conflict with the Sustainable Development Goal (SDG) agenda. Here, we carry out a multi-criteria sustainability assessment of large-scale bioenergy crop production throughout the 21st century (300 EJ in 2100) using a global land-use model. Our analysis indicates that large-scale bioenergy production without complementary measures results in negative effects on the following sustainability indicators: deforestation, CO2 emissions from land-use change, nitrogen losses, unsustainable water withdrawals and food prices. One of our main findings is that single-sector environmental protection measures next to large-scale bioenergy production are prone to involve trade-offs among these sustainability indicators—at least in the absence of more efficient land or water resource use. For instance, if bioenergy production is accompanied by forest protection, deforestation and associated emissions (SDGs 13 and 15) decline substantially whereas food prices (SDG 2) increase. However, our study also shows that this trade-off strongly depends on the development of future food demand. In contrast to environmental protection measures, we find that agricultural intensification lowers some side-effects of bioenergy production substantially (SDGs 13 and 15) without generating new trade-offs—at least among the sustainability indicators considered here. Moreover, our results indicate that a combination of forest and water protection schemes, improved fertilization efficiency, and agricultural intensification would reduce the side-effects of bioenergy production most comprehensively. However, although our study includes more sustainability indicators than previous studies on bioenergy side-effects, our study represents only a small subset of all indicators relevant for the SDG agenda. Based on this, we argue that the development of policies for regulating externalities of large-scale bioenergy production should rely on broad sustainability assessments to discover potential trade-offs with the SDG agenda before implementation.
Brockman, Robert; Ciarrochi, Joseph; Parker, Philip; Kashdan, Todd
2017-03-01
Most empirical studies of emotion regulation have relied on retrospective trait measures, and have not examined the link between daily regulatory strategies and every day emotional well-being. We used a daily diary methodology with multilevel modelling data analyses (n = 187) to examine the influence of three emotion regulation strategies (mindfulness, cognitive reappraisal and emotion suppression) on the experience of daily negative and positive affect. Our results suggested that daily mindfulness was associated with lower negative and higher positive affect whereas the converse pattern was found for daily emotion suppression; cognitive reappraisal was related to daily positive, but not negative affect. When daily mindfulness, suppression and reappraisal were included in the same models, these strategies predicted unique variance in emotional well-being. Random slope analyses revealed substantial variability in the utility of these strategies. Indeed the presumably "adaptive" cognitive reappraisal strategy seemed to confer no benefit to the regulation of negative affect in approximately half the sample. Additional analyses revealed that age moderates the effect of cognitive reappraisal on daily negative affect: Higher use of reappraisal was associated with more negative affect for adolescents (aged 17 to 19) but became associated with less negative affect with increasing age. We interpret these results in line with a contextual view of emotion regulation where no strategy is inherently "good" or "bad".
Alexandrescu, Sanda; Paulson, Vera; Dubuc, Adrian; Ligon, Azra; Lidov, Hart G
2018-05-14
The PHOX2B gene regulates neuronal maturation in the brain stem nuclei associated with cardiorespiratory function, and in the autonomic sympathetic and enteric nervous system. PHOX2B expression is a reliable immunomarker for peripheral neuroblastic tumors, however no systematic evaluation of CNS embryonal tumors was included in the studies. We encountered two cases in which the differential diagnosis included neuroblastoma and CNS embryonal tumor, and we hypothesized that PHOX2B immunostain would be helpful establishing the diagnosis. PHOX2B immunostain was performed on 29 pediatric cases, with adequate controls: 1 retroperitoneal embryonal tumor in a child with retinoblastoma (index1), 1 posterior fossa embryonal tumor in a child with a neuroblastoma (index2), 7 medulloblastomas, 4 atypical teratoid/rhabdoid tumors (ATRT), 4 retinoblastomas, 6 pineoblastomas, 4 embryonal tumors with multilayered rosettes (ETMR), and 2 CNS embryonal tumors, NEC. Cell lineage immunomarkers (GFAP, OLIG2, Synaptophysin, NeuN, CRX, PGP9.5), immunosurrogates for molecular alterations (beta-catenin, INI1, Lin28), array CGH and OncoPanel were performed as needed. Medulloblastomas, ATRTs, ETMRs, retinoblastomas and CNS embryonal tumors NOS were essentially negative for PHOX2B. Two (2) of 6 pineoblastomas had significant PHOX2B expression, while the rest were negative. Index1 was negative for PHOX2B and PGP 9.5, and positive for CRX, consistent with retinoblastoma. Index2 had diffuse PHOX2B expression, MYCN amplification and no copy number changes of medulloblastoma, in keeping with neuroblastoma. PHOX2B antibody is helpful in distinguishing between peripheral neuroblastic and CNS embryonal tumors, which are immunonegative, with the caveat that a subset of pineoblastomas has significant expression. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Yang, G-X; Sun, Y; Tsuneyama, K; Zhang, W; Leung, P S C; He, X-S; Ansari, A A; Bowlus, C; Ridgway, W M; Gershwin, M E
2016-08-01
During chronic inflammation, interleukin (IL)-22 expression is up-regulated in both CD4 and CD8 T cells, exerting a protective role in infections. However, in autoimmunity, IL-22 appears to have either a protective or a pathogenic role in a variety of murine models of autoimmunity and, by extrapolation, in humans. It is not clear whether IL-22 itself mediates inflammation or is a by-product of inflammation. We have taken advantage of the dominant negative form of transforming growth factor beta receptor type II (dnTGF-βRII) mice that develop both inflammatory bowel disease and autoimmune cholangitis and studied the role and the biological function of IL-22 by generating IL-22(-/-) dnTGF-βRII mice. Our data suggest that the influence of IL-22 on autoimmunity is determined in part by the local microenvironment. In particular, IL-22 deficiency exacerbates tissue injury in inflammatory bowel disease, but has no influence on either the hepatocytes or cholangiocytes in the same model. These data take on particular significance in the previously defined effects of IL-17A, IL-12p40 and IL-23p19 deficiency and emphasize that, in colitis, there is a dominant role of IL-23/T helper type 17 (Th17) signalling. Furthermore, the levels of IL-22 are IL-23-dependent. The use of cytokine therapy in patients with autoimmune disease has significant potential, but must take into account the overlapping and often promiscuous effects that can theoretically exacerbate inflammation. © 2016 British Society for Immunology.
Dixon-Gordon, Katherine L; Whalen, Diana J; Scott, Lori N; Cummins, Nicole D; Stepp, Stephanie D
2016-06-01
The transaction of adolescent's expressed negative affect and parental interpersonal emotion regulation are theoretically implicated in the development of borderline personality disorder (BPD). Although problem solving and support/validation are interpersonal strategies that foster emotion regulation, little is known about whether these strategies are associated with less BPD severity among adolescents. Adolescent girls (age 16; N = 74) and their mothers completed a conflict discussion task, and maternal problem solving, support/validation, and girls' negative affect were coded. Girls' BPD symptoms were assessed at four time points. A 3-way interaction of girls' negative affect, problem solving, and support/validation indicated that girls' negative affect was only associated with BPD severity in the context of low maternal support/validation and high maternal problem solving. These variables did not predict changes in BPD symptoms over time. Although high negative affect is a risk for BPD severity in adolescent girls, maternal interpersonal emotion regulation strategies moderate this link. Whereas maternal problem solving coupled with low support/validation is associated with a stronger negative affect-BPD relation, maternal problem solving paired with high support/validation is associated with an attenuated relationship.
Whalen, Diana J.; Scott, Lori N.; Cummins, Nicole D.; Stepp, Stephanie D.
2015-01-01
The transaction of adolescent’s expressed negative affect and parental interpersonal emotion regulation are theoretically implicated in the development of borderline personality disorder (BPD). Although problem solving and support/validation are interpersonal strategies that foster emotion regulation, little is known about whether these strategies are associated with less BPD severity among adolescents. Adolescent girls (age 16; N = 74) and their mothers completed a conflict discussion task, and maternal problem solving, support/validation, and girls’ negative affect were coded. Girls’ BPD symptoms were assessed at four time points. A 3-way interaction of girls’ negative affect, problem solving, and support/validation indicated that girls’ negative affect was only associated with BPD severity in the context of low maternal support/validation and high maternal problem solving. These variables did not predict changes in BPD symptoms over time. Although high negative affect is a risk for BPD severity in adolescent girls, maternal interpersonal emotion regulation strategies moderate this link. Whereas maternal problem solving coupled with low support/validation is associated with a stronger negative affect-BPD relation, maternal problem solving paired with high support/validation is associated with an attenuated relationship. PMID:27185969
Environmental Protection Agency, Protecting Children's Environmental Health
... Indicators of children's health - "America's Children and the Environment" report Scientific journal articles Standards and Regulations Regulations Regulatory development tracker Guidelines for Considering Children's Health in Economic ...
Zebrowitz, Leslie A; Boshyan, Jasmine; Ward, Noreen; Gutchess, Angela; Hadjikhani, Nouchine
2017-01-01
An older adult positivity effect, i.e., the tendency for older adults to favor positive over negative stimulus information more than do younger adults, has been previously shown in attention, memory, and evaluations. This effect has been attributed to greater emotion regulation in older adults. In the case of attention and memory, this explanation has been supported by some evidence that the older adult positivity effect is most pronounced for negative stimuli, which would motivate emotion regulation, and that it is reduced by cognitive load, which would impede emotion regulation. We investigated whether greater older adult positivity in the case of evaluative responses to faces is also enhanced for negative stimuli and attenuated by cognitive load, as an emotion regulation explanation would predict. In two studies, younger and older adults rated trustworthiness of faces that varied in valence both under low and high cognitive load, with the latter manipulated by a distracting backwards counting task. In Study 1, face valence was manipulated by attractiveness (low /disfigured faces, medium, high/fashion models' faces). In Study 2, face valence was manipulated by trustworthiness (low, medium, high). Both studies revealed a significant older adult positivity effect. However, contrary to an emotion regulation account, this effect was not stronger for more negative faces, and cognitive load increased rather than decreased the rated trustworthiness of negatively valenced faces. Although inconsistent with emotion regulation, the latter effect is consistent with theory and research arguing that more cognitive resources are required to process negative stimuli, because they are more cognitively elaborated than positive ones. The finding that increased age and increased cognitive load both enhanced the positivity of trustworthy ratings suggests that the older adult positivity effect in evaluative ratings of faces may reflect age-related declines in cognitive capacity rather than increases in the regulation of negative emotions.
Expressive Suppression Tendencies, Projection Bias in Memory of Negative Emotions, and Well-Being.
Chang, Valerie T; Overall, Nickola C; Madden, Helen; Low, Rachel S T
2018-02-01
The current research extends prior research linking negative emotions and emotion regulation tendencies to memory by investigating whether (a) naturally occurring negative emotions during routine weekly life are associated with more negatively biased memories of prior emotional experiences-a bias called projection; (b) tendencies to regulate emotions via expressive suppression are associated with greater projection bias in memory of negative emotions; and (c) greater projection bias in memory is associated with poorer future well-being. Participants (N = 308) completed a questionnaire assessing their general tendencies to engage in expressive suppression. Then, every week for 7 weeks, participants reported on (a) the negative emotions they experienced across the current week (e.g., "This week, I felt 'sad'"), (b) their memories of the negative emotions they experienced the prior week (e.g., "Last week, I felt 'sad'"), and (c) their well-being. First, participants demonstrated significant projection bias in memory: Greater negative emotions in a given week were associated with remembering emotions in the prior week more negatively than those prior emotions were originally reported. Second, projection bias in memory of negative emotions was greater for individuals who reported greater tendencies to regulate emotions via expressive suppression. Third, greater projection bias in memory of negative emotions was associated with reductions in well-being across weeks. These 3 novel findings indicate that (a) current negative emotions bias memory of past emotions, (b) this memory bias is magnified for people who habitually use expressive suppression to regulate emotions, and (c) this memory bias may undermine well-being over time. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
17 CFR 248.16 - Protection of Fair Credit Reporting Act.
Code of Federal Regulations, 2010 CFR
2010-04-01
... (CONTINUED) REGULATIONS S-P AND S-AM Regulation S-P: Privacy of Consumer Financial Information and Safeguarding Personal Information Relation to Other Laws; Effective Date § 248.16 Protection of Fair Credit... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Protection of Fair Credit...
Federal Register 2010, 2011, 2012, 2013, 2014
2013-07-25
...; Regulations Restricting the Sale and Distribution of Cigarettes and Smokeless Tobacco To Protect Children and... and Distribution of Cigarettes and Smokeless Tobacco to Protect Children and Adolescents'' has been... ``Regulations Restricting the Sale and Distribution of Cigarettes and Smokeless Tobacco to Protect Children and...
Federal Register 2010, 2011, 2012, 2013, 2014
2011-03-23
... Cigarettes and Smokeless Tobacco To Protect Children and Adolescents; Availability AGENCY: Food and Drug... Regulations Restricting the Sale and Distribution of Cigarettes and Smokeless Tobacco to Protect Children and... the Sale and Distribution of Cigarettes and Smokeless Tobacco to Protect Children and Adolescents...
76 FR 20569 - Horse Protection Act; Petition for Amendments to Regulations
Federal Register 2010, 2011, 2012, 2013, 2014
2011-04-13
... of Cruelty to Animals, the American Horse Protection Association, Inc., Friends of Sound Horses, Inc... DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service 9 CFR Part 11 [Docket No. APHIS-2011-0006] Horse Protection Act; Petition for Amendments to Regulations AGENCY: Animal and Plant...
75 FR 51968 - Outer Continental Shelf Air Regulations Consistency Update for Massachusetts
Federal Register 2010, 2011, 2012, 2013, 2014
2010-08-24
... comments to: Ida McDonnell, Air Permits, Toxics and Indoor Air Unit, Office of Ecosystem Protection, U.S... INFORMATION CONTACT: Ida E. McDonnell, Air Permits, Toxics and Indoor Air Unit, U.S. Environmental Protection... Continental Shelf Air Regulations Consistency Update for Massachusetts AGENCY: Environmental Protection Agency...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-14
..., direct final rule concerning household goods consumer protection. The direct final rule amended the... No. FMCSA-2012-0119] RIN 2126-AB52 Transportation of Household Goods in Interstate Commerce; Consumer Protection Regulations AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Direct final...
76 FR 7518 - Outer Continental Shelf Air Regulations Consistency Update for Alaska
Federal Register 2010, 2011, 2012, 2013, 2014
2011-02-10
... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 55 [EPA-R10-OAR-2011-0045; FRL-9265-3] Outer Continental Shelf Air Regulations Consistency Update for Alaska AGENCY: Environmental Protection Agency (``EPA... Greaves, Federal and Delegated Air Programs Unit, U.S. Environmental Protection Agency, Region 10, 1200...
40 CFR 52.1168a - Part D-Disapproval of Rules and Regulations.
Code of Federal Regulations, 2010 CFR
2010-07-01
... Department of Environmental Quality Engineering (DEQE) submitted a revision to the Massachusetts State... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Part D-Disapproval of Rules and Regulations. 52.1168a Section 52.1168a Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...
40 CFR 180.2010 - Threshold of regulation determinations.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Threshold of regulation determinations. 180.2010 Section 180.2010 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Pesticide Chemicals Not Requiring a Tolerance or an Exemption From...
40 CFR 180.2010 - Threshold of regulation determinations.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Threshold of regulation determinations. 180.2010 Section 180.2010 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Pesticide Chemicals Not Requiring a Tolerance or an Exemption From...
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…
Risk and Protective Factors for Psychological Adjustment and Grades among Adolescents.
ERIC Educational Resources Information Center
Voydanoff, Patricia; Donnelly, Brenda W.
1999-01-01
Examines the ways in which two risk factors: negative peer behavior and time spent without an adult, and two protective factors: adolescent resources and parental behavior influence psychological adjustment and grades among adolescents ages 10 to 17 (N=745). Results indicate that negative peer behavior is inversely related to adolescent well…
Positive Parenting as a Protective Resource for Parentally Bereaved Children
ERIC Educational Resources Information Center
Haine, Rachel A.; Wolchik, Sharlene A.; Sandler, Irwin N.; Millsap, Roger E.; Ayers, Tim S.
2006-01-01
Positive parenting was examined as a protective resource against the adverse effects of negative life events on parentally bereaved children's mental health problems. The sample consisted of 313 recently bereaved children ages 8 to 16 and their current caregiver. Both the compensatory (direct effect independent of negative life events) and the…
Sex differences and emotion regulation: an event-related potential study.
Gardener, Elyse K T; Carr, Andrea R; Macgregor, Amy; Felmingham, Kim L
2013-01-01
Difficulties in emotion regulation have been implicated as a potential mechanism underlying anxiety and mood disorders. It is possible that sex differences in emotion regulation may contribute towards the heightened female prevalence for these disorders. Previous fMRI studies of sex differences in emotion regulation have shown mixed results, possibly due to difficulties in discriminating the component processes of early emotional reactivity and emotion regulation. The present study used event-related potentials (ERPs) to examine sex differences in N1 and N2 components (reflecting early emotional reactivity) and P3 and LPP components (reflecting emotion regulation). N1, N2, P3, and LPP were recorded from 20 men and 23 women who were instructed to "increase," "decrease," and "maintain" their emotional response during passive viewing of negative images. Results indicated that women had significantly greater N1 and N2 amplitudes (reflecting early emotional reactivity) to negative stimuli than men, supporting a female negativity bias. LPP amplitudes increased to the "increase" instruction, and women displayed greater LPP amplitudes than men to the "increase" instruction. There were no differences to the "decrease" instruction in women or men. These findings confirm predictions of the female negativity bias hypothesis and suggest that women have greater up-regulation of emotional responses to negative stimuli. This finding is highly significant in light of the female vulnerability for developing anxiety disorders.
[Law and the phase of life old age].
Klie, Thomas
2017-06-01
In spite of the greatly increased role, which the law attributes to the design of individual life styles and living of elderly people, there is no special legal area known in the German legal system, such as "rights of the elderly", which is the case in the field of the youth law. Special legal regulations covering the concerns/issues of elderly people were always considered to be in danger, as they may have the potential to discrimination, either in a positive or negative way. Due to this fact, the rights of the elderly can be described as synthetic and are subject to constant changes, as can be observed within the pension act. The legal areas and legal regulations, which are of particular importance for the life style and living situations of elderly people are presented. The legal need for action regarding the special protection of vulnerable elderly people is discussed and in the further course utilized for a conception of "rights of the elderly".
Gamma-secretase inhibitors reverse glucocorticoid resistance in T-ALL
Real, Pedro J.; Tosello, Valeria; Palomero, Teresa; Castillo, Mireia; Hernando, Eva; de Stanchina, Elisa; Sulis, Maria Luisa; Barnes, Kelly; Sawai, Catherine; Homminga, Irene; Meijerink, Jules; Aifantis, Iannis; Basso, Giuseppe; Cordon-Cardo, Carlos; Ai, Walden; Ferrando, Adolfo
2009-01-01
Summary Gamma-secretase inhibitors (GSIs) block the activation of oncogenic NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL). However, limited antileukemic cytotoxicity and severe gastrointestinal toxicity have restricted the clinical application of these targeted drugs. Here we show that combination therapy with GSIs plus glucocorticoids can improve the antileukemic effects of GSIs and reduce their gut toxicity in vivo. Inhibition of NOTCH1 signaling in glucocorticoid-resistant T-ALL restored glucocorticoid receptor auto-up-regulation and induced apoptotic cell death through induction of BIM expression. GSI treatment resulted in cell cycle arrest and accumulation of goblet cells in the gut mediated by upregulation of Klf4, a negative regulator of cell cycle required for goblet cell differentiation. In contrast, glucocorticoid treatment induced transcriptional upregulation of Ccnd2 and protected mice from developing intestinal goblet cell metaplasia typically induced by inhibition of NOTCH signaling with GSIs. These results support a role for glucocorticoids plus GSIs in the treatment of glucocorticoid-resistant T-ALL. PMID:19098907
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
European Long-Term Care Programs: Lessons for Community Living Assistance Services and Supports?
Nadash, Pamela; Doty, Pamela; Mahoney, Kevin J; von Schwanenflugel, Matthias
2012-01-01
Objective To uncover lessons from abroad for Community Living Assistance Services and Supports (CLASS), a federally run voluntary public long-term care (LTC) insurance program created under the Accountable Care Act of 2010. Data Sources Program administrators and policy researchers from Austria, England, France, Germany, and the Netherlands. Study Design Qualitative methods focused on key parameters of cash for care: how programs set benefit levels; project expenditures; control administrative costs; regulate the use of benefits; and protect workers. Data Collection/Extraction Methods Structured discussions were conducted during an international conference of LTC experts, followed by personal meetings and individual correspondence. Principal Findings Germany's self-financing mandate and tight targeting of benefits have resulted in a solvent program with low premiums. Black markets for care are likely in the absence of regulation; France addresses this via a unique system ensuing legal payment of workers. Conclusions Programs in the five countries studied have lessons, both positive and negative, relevant to CLASS design. PMID:22091672
Cdon acts as a Hedgehog decoy receptor during proximal-distal patterning of the optic vesicle
Cardozo, Marcos Julián; Sánchez-Arrones, Luisa; Sandonis, África; Sánchez-Camacho, Cristina; Gestri, Gaia; Wilson, Stephen W.; Guerrero, Isabel; Bovolenta, Paola
2014-01-01
Patterning of the vertebrate optic vesicle into proximal/optic stalk and distal/neural retina involves midline-derived Hedgehog (Hh) signalling, which promotes stalk specification. In the absence of Hh signalling, the stalks are not specified, causing cyclopia. Recent studies showed that the cell adhesion molecule Cdon forms a heteromeric complex with the Hh receptor Patched 1 (Ptc1). This receptor complex binds Hh and enhances signalling activation, indicating that Cdon positively regulates the pathway. Here we show that in the developing zebrafish and chick optic vesicle, in which cdon and ptc1 are expressed with a complementary pattern, Cdon acts as a negative Hh signalling regulator. Cdon predominantly localizes to the basolateral side of neuroepithelial cells, promotes the enlargement of the neuroepithelial basal end-foot and traps Hh protein, thereby limiting its dispersion. This Ptc-independent function protects the retinal primordium from Hh activity, defines the stalk/retina boundary and thus the correct proximo-distal patterning of the eye. PMID:25001599
The role of emotions in UV protection intentions and behaviors.
Mahler, Heike I M
2014-01-01
Two studies examined the role of emotions, relative to cognitions, in predicting sun protection intentions and practices. In Study 1, 106 females were assessed for baseline sun protection, ultraviolet (UV) radiation exposure-related cognitions (perceived susceptibility to skin damage, self-efficacy for regular sunscreen use, perceived costs of sun protection use, perceived rewards of tanning), anticipated negative mood following future risky UV behavior, and future sun protection intentions. Self-reported sun protection behavior was then assessed in the same participants five weeks later. The results of Study 1 demonstrated that the extent to which participants' expected to experience negative feelings if they engaged in future risky UV behavior predicted their intentions to sun protect and their subsequent sun protection behaviors independent of their UV radiation exposure-related cognitions. In Study 2, in addition to the assessments collected in Study 1, participants were exposed to an appearance-based intervention that included visual images of their existing skin damage and were then assessed for their emotional reactions to the intervention. The results replicated those of Study 1 and, in addition, showed that negative emotional reactions to the intervention predicted future sun protection intentions and self-reported behaviors at follow-up, independent of the various cognitive factors that are central to prominent models of health behavior. These studies provide preliminary support for the development of expanded health behavior models that incorporate anticipated and experienced emotions.
Cai, Yun; Zhao, Boxin; Liang, Qianying; Zhang, Yunqi; Cai, Jieying; Li, Guofeng
2017-08-15
Triple negative breast cancer(TNBC) has generated growing interests due to its aggressive biologic behavior and absence of targeted therapy approach. Glycyrrhizin(GL) from licorice root and its metabolite, glycyrrhetinic acid(GA) have shown extensive bioactivities in clinic. Here, we demonstrate that GL and GA have contrary anti-cancer effect on TNBC MDA-MB-231 cells. Beside its inhibition of cell proliferation, GA at non-cytotoxic concentration showed synergistic effect in combination with anti-cancer drug, etoposide(VP-16). Specifically, GA enhanced cytotoxicity through regulating topoisomerase IIα(TOPO 2A) targeted by etoposide. GA sensitized the cells to etoposide through elevating TOPO 2A with a 2.4 fold rate at 12h. From 12 to 48h, GA halved the expression of TOPO 2A and stimulated apoptosis, which exhibited its antineoplastic effect. Our experiments showed that GSH depletion, modulation of MAPK and AKT pathways accounted for the regulation of topoisomerase IIα and apoptosis. However, GL showed protection and detoxication by decreasing reactive oxygen species generation, maintaining GSH and differentially modulating apoptosis, AKT pathway, ERK and JNK of MAPK pathway. Collectively, our results demonstrate that GA, instead of GL, is a better candidate for TNBC treatment because of its anti-cancer effect and sensitization of topoisomerase IIα inhibitor. Copyright © 2017 Elsevier B.V. All rights reserved.
Guang, Yu; Feng, Zhengzhi; Yang, Guoyu; Yang, Yaling; Wang, Lifei; Dai, Qin; Hu, Chaobing; Liu, Keyu; Zhang, Rui; Xia, Fan; Zhao, Mengxue
2017-12-15
In China, children under 18 years old who are left at rural residences for at least 6 months by either one or both of their parents migrating to work in cities are called "left-behind children (LBC)". Due to restricted family support, they are at a greater risk of developing depressive symptoms than non-left-behind children (NLBC). The objective of this study is to explore how depressive symptoms and stress induced by negative life events such as interpersonal conflicts, punishment and loss, as well as their relationships vary for LBC with different left-behind-related characteristics. Using data from a large school-based survey conducted in Chongqing between December 2012 and June 2013, we first identified the differences in depressive symptoms and negative-event-induced stress between LBC and NLBC, and then analyzed the variances among LBC with different left-behind-related characteristics. The data was analyzed with Chi-square test, MANCOVA, ANCOVA, ANOVA, T-test and hierarchical multiple regression analyses. We found that LBC were more stressed when experiencing negative events and had more depressive symptoms than NLBC. Children left behind by both parents were most depressed. Negative-event-induced stress and communication on life difficulties with migrant parents were risk factors for depressive symptoms, whereas adequate communication on academic performance or children's feelings was a protective factor against depressive symptoms. Communication duration and frequency, communication by visiting, communication on academic performance, life difficulties and children's feelings moderated the relationship between stress and depressive symptoms, respectively. Duration of separation, communication duration and frequency, communication on academic performance, learning difficulties and children's feelings moderated the relation between the type of parental migration and depressive symptoms, respectively. Our findings suggest that children left behind by both parents should be the focus of public attention for their higher susceptibility to stress-related depression. To help LBC stay mentally healthy, governments need to formulate regulations contributing to LBC's family reunion, communities need to involve more residents to attend LBC as "surrogate parents" and teach migrant parents to communicate with LBC properly, and schools need to teach LBC how to deal with stress and communicate with migrant parents.
Distract or reappraise? Age-related differences in emotion-regulation choice.
Scheibe, Susanne; Sheppes, Gal; Staudinger, Ursula M
2015-12-01
Does aging impact strategy choice with regard to regulating negative emotions? Based on the assumption that older adults are highly motivated to quickly defuse negative states, we predicted that older adults, relative to young adults, would show an increased preference for distraction (a cognitive disengagement strategy) over reappraisal (a cognitive engagement strategy) in the face of negative material. A stronger preference for distraction, in turn, should be associated with higher affective well-being at older ages, as it helps to avoid high physiological arousal. Young (19-28 years, n = 38) and older (65-75 years, n = 39) adults completed a laboratory task of emotion-regulation choice in which they viewed negative pictures of high and low intensity and chose between distraction and reappraisal to regulate their emotional response. Confirming predictions, age was associated with an increased preference to choose distraction over reappraisal. Among older but not young adults, the relative preference for distraction to reappraisal predicted higher state-affective well-being. In addition, across age groups, the preference for distraction over reappraisal was positively predicted by stimulus intensity and negatively by cognitive resources. Findings support the notion of an age-related shift toward disengagement strategies to regulate negative emotions, which maps onto older adults' prohedonic orientation and holds affective benefits. (c) 2015 APA, all rights reserved).
[Attentional bias and emotional suppression in borderline personality disorder].
Fernando, Silvia Carvalho; Griepenstroh, Julia; Urban, Sabine; Driessen, Martin; Beblo, Thomas
2014-01-01
Emotion regulation dysfunctions marked by negative affectivity are a core feature of borderline personality disorder (BPD). In addition, patients with BPD show disturbed attentional processes which become particularly apparent in the domain of selective attention when emotional stimuli are presented (negative attentional bias). Assuming that emotion regulation is linked to attentional deployment processes, this study aimed (1) to determine whether a negative attentional bias is established by using film clips of fearful faces and (2) to investigate the association between dysfunctional emotion regulation strategies (emotional suppression) and negative attention bias in BPD. We investigated 18 inpatients with BPD and 18 healthy control participants using the modified version of the fearful face-paradigm to assess the inhibition of emotional stimuli. We also administered self-report emotion regulation questionnaires. Compared to the healthy controls, patients with BPD showed significant longer reaction times during the emotional versus the neutral film stimuli in the modified fearful face-paradigm. With regard to the second hypothesis, we failed to find an association between the negative attentional bias and the habitual use of emotional suppression in BPD. In this study, we could confirm an attentional bias for negative stimuli, using complex, dynamic material. Future studies need to address the impact of confounding variables (e. g. comorbid disorders) on the relationship between maladaptive emotion regulation and selective attentional bias.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Waseda, Masazumi; Arimura, Sumimasa; Shimura, Eri
Appropriate immune responses and mucosal barrier functions are required for the maintenance of intestinal homeostasis. Defects in this defense system may lead to inflammatory disorders such as inflammatory bowel disease. Downstream of tyrosine kinases 1 (Dok-1) and its closest homolog, Dok-2, are preferentially expressed in immune cells, and play essential roles in the negative regulation of multiple signaling pathways in both innate and adaptive immunity. However, the function of these proteins in intestinal homeostasis remained unclear. Here we show that Dok-1/-2 double knockout (DKO) mice were highly susceptible to dextran sodium sulfate (DSS)-induced colitis compared with Dok-1 or Dok-2 singlemore » KO and wild type (WT) mice. Furthermore, DSS-treated Dok-1/-2 DKO mice exhibited increased colonic tissue damage accompanied by reduced proliferation of the epithelial cells relative to WT controls, suggesting that Dok-1/-2 DKO mice have defects in the repair of intestinal epithelial lesions. In addition, the levels of the Th17 cytokines IL-17A and IL-22, which have protective roles in DSS-induced colitis, were reduced in DSS-treated Dok-1/-2 DKO mice compared with WT mice. Taken together, our results demonstrate that Dok-1 and Dok-2 negatively regulate intestinal inflammation, apparently through the induction of IL-17A and IL-22 expression. - Highlights: • Dok-1 and Dok-2 play a cooperative role in protection against DSS-induced colitis. • Dok-1/-2 double KO (DKO) mice show extensive ulceration of the colon after DSS treatment. • Proliferation of colonic epithelium is inhibited in DSS-treated Dok-1/-2 DKO mice. • Expression of IL-17A and IL-22 is reduced in the colon of DSS-treated Dok-1/-2 DKO mice.« less
Ding, Saidan; Zhuge, Weishan; Wang, Xuebao; Yang, Jianjing; Lin, Yuanshao; Wang, Chengde; Hu, Jiangnan; Zhuge, Qichuan
2017-01-01
Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95–nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95–nNOS interactions in MHE. PMID:28932186
Xu, Yan; Xing, Yawei; Xu, Yanjie; Huang, Chahua; Bao, Huihui; Hong, Kui; Cheng, Xiaoshu
2016-12-01
We know that silencing Bim, a pro-apoptosis protein, significantly attenuates glucose and oxygen-deprived induced apoptosis in cardiomyocytes. However, the mechanisms underlying the regulation of the Bim activation in the heart have remained unknown. Pim-2 is one of three Pim serine/threonine kinase family members thought to be involved in cell survival and proliferation. H9c2 cardiomyocytes were subjected to a hypoxia/reoxygenation (H/R) condition in vitro, mimicking ischemic/reperfusion injury in vivo. H/R augmented the expression of Bim, Cyt C, and Pim-2 and induced H9c2 cell apoptosis. Overexpression of Pim-2 attenuated apoptosis which induced by H/R in H9c2 cells, via downregulation of Bim and Cyt C expression. Silencing of Pim-2 promoted H/R-induced apoptosis via upregulation of Bim and Cyt C expression. Co-IP revealed the interaction between Pim-2 and Bim protein, with Bim Ser 65 phosphorylated by Pim-2. Furthermore, blocking proteasome activity by MG132 prevented Bim degradation, and Bim S65A mutation could reverse the anti-apoptotic role of Pim-2 which induced by H/R. These data demonstrated that Pim-2 is a novel Bim-interacting protein, which negatively regulates Bim degradation and protects H9c2 cardiomyocytes from H/R-induced apoptosis. Copyright © 2016 Elsevier B.V. All rights reserved.
Commentary: Ethical Issues of Current Health-Protection Policies on Low-Dose Ionizing Radiation
Socol, Yehoshua; Dobrzyński, Ludwik; Doss, Mohan; Feinendegen, Ludwig E.; Janiak, Marek K.; Miller, Mark L.; Sanders, Charles L.; Scott, Bobby R.; Ulsh, Brant; Vaiserman, Alexander
2014-01-01
The linear no-threshold (LNT) model of ionizing-radiation-induced cancer is based on the assumption that every radiation dose increment constitutes increased cancer risk for humans. The risk is hypothesized to increase linearly as the total dose increases. While this model is the basis for radiation safety regulations, its scientific validity has been questioned and debated for many decades. The recent memorandum of the International Commission on Radiological Protection admits that the LNT-model predictions at low doses are “speculative, unproven, undetectable and ‘phantom’.” Moreover, numerous experimental, ecological, and epidemiological studies show that low doses of sparsely-ionizing or sparsely-ionizing plus highly-ionizing radiation may be beneficial to human health (hormesis/adaptive response). The present LNT-model-based regulations impose excessive costs on the society. For example, the median-cost medical program is 5000 times more cost-efficient in saving lives than controlling radiation emissions. There are also lives lost: e.g., following Fukushima accident, more than 1000 disaster-related yet non-radiogenic premature deaths were officially registered among the population evacuated due to radiation concerns. Additional negative impacts of LNT-model-inspired radiophobia include: refusal of some patients to undergo potentially life-saving medical imaging; discouragement of the study of low-dose radiation therapies; motivation for radiological terrorism and promotion of nuclear proliferation. PMID:24910586
A teleost CD46 is involved in the regulation of complement activation and pathogen infection.
Li, Mo-Fei; Sui, Zhi-Hai; Sun, Li
2017-11-03
In mammals, CD46 is involved in the inactivation of complement by factor I (FI). In teleost, study on the function of CD46 is very limited. In this study, we examined the immunological property of a CD46 molecule (CsCD46) from tongue sole, a teleost species with important economic value. We found that recombinant CsCD46 (rCsCD46) interacted with FI and inhibited complement activation in an FI-dependent manner. rCsCD46 also interacted with bacterial pathogens via a different mechanism to that responsible for the FI interaction, involving different rCsCD46 sites. Cellular study showed that CsCD46 was expressed on peripheral blood leukocytes (PBL) and protected the cells against the killing effect of complement. When the CsCD46 on PBL was blocked by antibody before incubation of the cells with bacterial pathogens, cellular infection was significantly reduced. Consistently, when tongue sole were infected with bacterial pathogens in the presence of rCsCD46, tissue dissemination and survival of the pathogens were significantly inhibited. These results provide the first evidence to indicate that CD46 in teleosts negatively regulates complement activation via FI and protects host cells from complement-induced damage, and that CD46 is required for optimal bacterial infection probably by serving as a receptor for the bacteria.
Inter Individual Variations of the Fish Skin Microbiota: Host Genetics Basis of Mutualism?
Boutin, Sébastien; Sauvage, Christopher; Bernatchez, Louis; Audet, Céline; Derome, Nicolas
2014-01-01
The commensal microbiota of fish skin is suspected to provide a protection against opportunist infections. The skin of fish harbors a complex and diverse microbiota that closely interacts with the surrounding water microbial communities. Up to now there is no clear evidence as to whether the host regulates the recruitment of environmental bacteria to build a specific skin microbiota. To address this question, we detected Quantitative Trait Loci (QTL) associated with the abundance of specific skin microbiota bacterial strains in brook charr (Salvelinus fontinalis), combining 16S RNA tagged-amplicon 454 pyrosequencing with genetic linkage analysis. Skin microbiota analysis revealed high inter-individual variation among 86 F2 fish progeny based upon the relative abundance of bacterial operational taxonomic units (OTUs). Out of those OTUs, the pathogenic strain Flavobacterium psychrophilum and the non-pathogenic strain Methylobacterium rhodesianum explained the majority of inter-individual distances. Furthermore, a strong negative correlation was found between Flavobacterium and Methylobacterium, suggesting a mutually competitive relationship. Finally, after considering a total of 266 markers, genetic linkage analysis highlighted three major QTL associated with the abundance of Lysobacter, Rheinheimera and Methylobacterium. All these three genera are known for their beneficial antibacterial activity. Overall, our results provide evidence that host genotype may regulate the abundance of specific genera among their surface microbiota. They also indicate that Lysobacter, Rheinheimera and Methylobacterium are potentially important genera in providing protection against pathogens. PMID:25068850
Inter individual variations of the fish skin microbiota: host genetics basis of mutualism?
Boutin, Sébastien; Sauvage, Christopher; Bernatchez, Louis; Audet, Céline; Derome, Nicolas
2014-01-01
The commensal microbiota of fish skin is suspected to provide a protection against opportunist infections. The skin of fish harbors a complex and diverse microbiota that closely interacts with the surrounding water microbial communities. Up to now there is no clear evidence as to whether the host regulates the recruitment of environmental bacteria to build a specific skin microbiota. To address this question, we detected Quantitative Trait Loci (QTL) associated with the abundance of specific skin microbiota bacterial strains in brook charr (Salvelinus fontinalis), combining 16S RNA tagged-amplicon 454 pyrosequencing with genetic linkage analysis. Skin microbiota analysis revealed high inter-individual variation among 86 F2 fish progeny based upon the relative abundance of bacterial operational taxonomic units (OTUs). Out of those OTUs, the pathogenic strain Flavobacterium psychrophilum and the non-pathogenic strain Methylobacterium rhodesianum explained the majority of inter-individual distances. Furthermore, a strong negative correlation was found between Flavobacterium and Methylobacterium, suggesting a mutually competitive relationship. Finally, after considering a total of 266 markers, genetic linkage analysis highlighted three major QTL associated with the abundance of Lysobacter, Rheinheimera and Methylobacterium. All these three genera are known for their beneficial antibacterial activity. Overall, our results provide evidence that host genotype may regulate the abundance of specific genera among their surface microbiota. They also indicate that Lysobacter, Rheinheimera and Methylobacterium are potentially important genera in providing protection against pathogens.
Ding, Saidan; Zhuge, Weishan; Wang, Xuebao; Yang, Jianjing; Lin, Yuanshao; Wang, Chengde; Hu, Jiangnan; Zhuge, Qichuan
2017-01-01
Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95-nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95-nNOS interactions in MHE.
Kwak, Dong Shin; Lee, Oh Young; Lee, Kang Nyeong; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon
2016-05-23
DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.
Images of the Self and Self-Esteem: Do Positive Self-Images Improve Self-Esteem in Social Anxiety?
Hulme, Natalie; Hirsch, Colette; Stopa, Lusia
2012-01-01
Negative self-images play an important role in maintaining social anxiety disorder. We propose that these images represent the working self in a Self-Memory System that regulates retrieval of self-relevant information in particular situations. Self-esteem, one aspect of the working self, comprises explicit (conscious) and implicit (automatic) components. Implicit self-esteem reflects an automatic evaluative bias towards the self that is normally positive, but is reduced in socially anxious individuals. Forty-four high and 44 low socially anxious participants generated either a positive or a negative self-image and then completed measures of implicit and explicit self-esteem. Participants who held a negative self-image in mind reported lower implicit and explicit positive self-esteem, and higher explicit negative self-esteem than participants holding a positive image in mind, irrespective of social anxiety group. We then tested whether positive self-images protected high and low socially anxious individuals equally well against the threat to explicit self-esteem posed by social exclusion in a virtual ball toss game (Cyberball). We failed to find a predicted interaction between social anxiety and image condition. Instead, all participants holding positive self-images reported higher levels of explicit self-esteem after Cyberball than those holding negative self-images. Deliberate retrieval of positive self-images appears to facilitate access to a healthy positive implicit bias, as well as improving explicit self-esteem, whereas deliberate retrieval of negative self-images does the opposite. This is consistent with the idea that negative self-images may have a causal, as well as a maintaining, role in social anxiety disorder. PMID:22439697
2009-01-01
Background While much attention is focused on national policies intended to protect human health from environmental hazards, states can also prevent environmentally mediated disease through legislation and regulation. However, relatively few analyses have examined the extent to which states protect children from chemical factors in the environment. Methods Using Lexis Nexis and other secondary sources, we systematically reviewed environmental regulation and legislation in the fifty states and the District of Columbia as of July 2007 intended to protect children against neurodevelopmental disabilities and asthma. Results States rarely address children specifically in environmental regulation and legislation, though many state regulations go far to limit children's exposures to environmental hazards. Northeast and Midwest states have implemented model regulation of mercury emissions, and regulations in five states set exposure limits to volatile organic compound emissions that are more stringent than US Environmental Protection Agency standards. Discussion Differences in state environmental regulation and legislation are likely to lead to differences in exposure, and thus to impacts on children's health. The need for further study should not inhibit other states and the federal government from pursuing the model regulation and legislation we identified to prevent diseases of environmental origin in children. PMID:19323818
Gerhart, James I; Burns, John W; Bruehl, Stephen; Smith, David A; Post, Kristina M; Porter, Laura S; Schuster, Erik; Buvanendran, Asokumar; Fras, Anne Marie; Keefe, Francis J
2017-11-13
Chronic pain is associated with elevated negative emotions, and resources needed to adaptively regulate these emotions can be depleted during prolonged pain. Studies of links between pain, function, and negative emotions in people with chronic pain, however, have focused almost exclusively on relationships among mean levels of these factors. Indexes that may reflect aspects of emotion regulation have typically not been analyzed. We propose that 1 index of emotion regulation is variability in emotion over time as opposed to average emotion over time. The sample was 105 people with chronic low back pain and 105 of their pain-free spouses. They completed electronic diary measures 5x/d for 14 consecutive days, producing 70 observations per person from which we derived estimates of within-subject variance in negative emotions. Location-scale models were used to simultaneously model predictors of both mean level and variance in patient negative emotions over time. Patients reported significantly more variability in negative emotions compared to their spouses. Patients who reported higher average levels of pain, pain interference, and downtime reported significantly higher levels of variability in negative emotions. Spouse-observed pain and pain behaviors were also associated with greater variability in patients' negative emotions. Test of the inverse associations between negative emotion level and variability in pain and function were significant but weaker in magnitude. These findings support the notion that chronic pain may erode negative emotion regulation resources, to the potential detriment of intra- and inter-personal function.
12 CFR 1233.5 - Protection from liability for reports.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Protection from liability for reports. 1233.5 Section 1233.5 Banks and Banking FEDERAL HOUSING FINANCE AGENCY ENTITY REGULATIONS REPORTING OF FRAUDULENT... law or regulation, any constitution, law, or regulation of any State or political subdivision of any...
12 CFR 1233.5 - Protection from liability for reports.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 12 Banks and Banking 10 2014-01-01 2014-01-01 false Protection from liability for reports. 1233.5 Section 1233.5 Banks and Banking FEDERAL HOUSING FINANCE AGENCY ENTITY REGULATIONS REPORTING OF FRAUDULENT... law or regulation, any constitution, law, or regulation of any State or political subdivision of any...
Workplace incivility and new graduate nurses' mental health: the protective role of resiliency.
Laschinger, Heather K; Wong, Carol; Regan, Sandra; Young-Ritchie, Carol; Bushell, Pamela
2013-01-01
The aim of this study was to examine the relationships between coworker, physician, and supervisor workplace incivility and new graduate nurses' mental health and the protective role of personal resiliency. Positive interpersonal relationships in healthcare work environments are important for new graduate nurses' career transition and commitment. Workplace incivility threatens new graduate nurses' health and well-being. Personal resiliency helps employees to recover from negative stressors and may protect new nurses from the negative effects of workplace incivility. We surveyed 272 new graduate nurses in Ontario to explore the influence of 3 forms of workplace incivility and personal resiliency on new nurses' mental health. All sources of incivility were related to poor mental health. Results suggest that personal resiliency may protect nurses from the negative effects of incivility. New nurses are experiencing workplace incivility from a variety of sources in their work environments, which have detrimental effects on their workplace well-being.
It Takes a Village: Protecting Rural African American Youth in the Context of Racism
Murry, Velma McBride; Hurt, Tera R.; Chen, Yi-fu; Brody, Gene H.; Simons, Ronald L.; Cutrona, Carolyn; Gibbons, Frederick X.
2009-01-01
Prior research demonstrates negative consequences of racism, however, little is known about community, parenting, and intrapersonal mechanisms that protect youth. Using a mixed-methods approach, this study illuminated linkages between positive and negative contextual influences on rural African American adolescent outcomes. Quantitative results provide support for Structural Ecosystems Theory, in that the influence of discrimination and collective socialization on adolescent outcomes was mediated by racial socialization and positive parenting. Parenting and community influences contributed to adolescent racial identity and self image, which protected against common negative responses to racism; including academic underachievement, succumbing to peer pressure, and aggressive tendencies. Qualitative results indicate that current measures of discrimination may underestimate adolescents’ experiences. Adolescents reported racist experiences in the domains of school, peers, and with the police (males only). Moreover, qualitative findings echoed and expanded quantitative results with respect to the importance of the protective nature of parents and communities. PMID:19636716
Influence of Age, Thought Content, and Anxiety on Suppression of Intrusive Thoughts
Beadel, Jessica R.; Green, Jennifer S.; Hosseinbor, Shahrzad; Teachman, Bethany A.
2013-01-01
Understanding differences in responses following attempts to suppress versus simply monitor intrusive thoughts is important given the established relationship between intrusive thinking and numerous forms of psychopathology. Moreover, these differences may vary as a function of age. Because of the links between aging and both enhancement in emotion regulation skills and decline in inhibition skills, older and younger adults were expected to differ in their responses (e.g., experience of negative affect and thought recurrence) to attempts at suppressing intrusive thoughts. This study examined whether efforts to suppress thought content that varied in valence and age-relevance differentially affected older (N = 40, aged 66–92) and younger (N = 42, aged 16–25) adults’ ability to inhibit intrusive thought recurrence and their resulting negative affect. Interestingly, older adults experienced less recurrence for most thoughts than younger adults. Also, for several dependent variables (negative affect and perceived difficulty suppressing intrusive thoughts), older adults showed less decline in their magnitude of response across thinking periods (i.e., from suppression to monitoring) than did younger adults. These age effects were not generally moderated by level of trait anxiety, though higher anxiety did predict intrusive thought responding in expected directions, such as greater negative affect. These findings point to independent influences of age and anxiety, and suggest a complex mix of risk and protective factors for older adults’ responses to intrusive thoughts. PMID:23395408
Vanderhasselt, Marie-Anne; Kühn, Simone; De Raedt, Rudi
2011-06-01
Depressive brooding is considered a maladaptive ruminative-thinking style that has been shown to be highly correlated with major depression. The present study in healthy participants employed event-related fMRI to uncover the neural underpinnings of emotional disengagement as it relates to depressive brooding. Thirty-four healthy, never depressed individuals performed an emotional go/no-go task with a rapid presentation of emotional faces. We focused on the contrast of inhibiting sad (happy/no-go) versus inhibiting happy (sad/no-go) information. This contrast allowed us to assess possible difficulties in disengaging from emotionally negative, as compared with emotionally positive, faces. At the behavioral level, only in high brooders were higher self-reported brooding scores correlated with more errors when sad information was inhibited, relative to happy information. At the neural level, across all participants, brooding scores were positively correlated with activity in the right dorsolateral prefrontal cortex (DLPFC; BA 46), implying that high brooders show higher DLPFC involvement when successfully disengaging from a series of negative stimuli. These results may suggest that healthy individuals who report a high brooding thinking style need to recruit more attentional control in order to disengage successfully from negative information, in a way that may be related to emotion regulation strategies. These mechanisms might protect them from developing depressive symptoms.
Attachment Security and Child's Empathy: The Mediating Role of Emotion Regulation
ERIC Educational Resources Information Center
Panfile, Tia M.; Laible, Deborah J.
2012-01-01
The current study examined the influence of multiple factors on individual differences in empathy; namely, attachment, negative emotionality, and emotion regulation. A total of 63 mothers completed the Attachment Q-set and questionnaires about their children's empathy, negative emotionality, and emotion regulation when children were 3 years old.…
Phan, Vernon T.; Ding, Vivianne W.; Li, Fenglei; Chalkley, Robert J.; Burlingame, Alma; McCormick, Frank
2010-01-01
The neurofibromatosis type 1 (NF1) gene encodes the GTPase-activating protein (GAP) neurofibromin, which negatively regulates Ras activity. The yeast Saccharomyces cerevisiae has two neurofibromin homologs, Ira1 and Ira2. To understand how these proteins are regulated, we utilized an unbiased proteomics approach to identify Ira2 and neurofibromin binding partners. We demonstrate that the Gpb1/Krh2 protein binds and negatively regulates Ira2 by promoting its ubiquitin-dependent proteolysis. We extended our findings to show that in mammalian cells, the ETEA/UBXD8 protein directly interacts with and negatively regulates neurofibromin. ETEA contains both UBA and UBX domains. Overexpression of ETEA downregulates neurofibromin in human cells. Purified ETEA, but not a mutant of ETEA that lacks the UBX domain, ubiquitinates the neurofibromin GAP-related domain in vitro. Silencing of ETEA expression increases neurofibromin levels and downregulates Ras activity. These findings provide evidence for conserved ubiquitination pathways regulating the RasGAP proteins Ira2 (in yeast) and neurofibromin (in humans). PMID:20160012
Kendall, Megan; Hamill, Declan
2016-01-01
Abstract Drug regulators in Canada and in other nations require innovative pharmaceutical companies to submit undisclosed clinical or other data as a condition of approving the marketing of new pharmaceutical products—the origination of which involves considerable effort and investment. Data protection regulations were enacted in Canada in 2006, which—to some extent—closed a loophole in intellectual property law that had previously left innovative companies with no effective data protection for their clinical data. Although the regulations were intended to clarify and effectively implement Canada's international treaty obligations in the spirit of innovation, a review of Canada's first decade of effective data protection shows that Health Canada and Canadian courts have interpreted the scope of data protection for innovative drugs in a narrow manner that undermines and is inconsistent with the intent of the regulations. As the 10-year anniversary of data protection in Canada is this year (2016), this article demonstrates the need to advance Canada's data protection regime into one that consistently contributes to the promotion of investment in pharmaceutical research and development, to the mutual advantage of innovators and patients, in a manner conducive to the social and economic welfare of Canadians. PMID:28077911
Kendall, Megan; Hamill, Declan
2016-12-01
Drug regulators in Canada and in other nations require innovative pharmaceutical companies to submit undisclosed clinical or other data as a condition of approving the marketing of new pharmaceutical products-the origination of which involves considerable effort and investment. Data protection regulations were enacted in Canada in 2006, which-to some extent-closed a loophole in intellectual property law that had previously left innovative companies with no effective data protection for their clinical data. Although the regulations were intended to clarify and effectively implement Canada's international treaty obligations in the spirit of innovation, a review of Canada's first decade of effective data protection shows that Health Canada and Canadian courts have interpreted the scope of data protection for innovative drugs in a narrow manner that undermines and is inconsistent with the intent of the regulations. As the 10-year anniversary of data protection in Canada is this year (2016), this article demonstrates the need to advance Canada's data protection regime into one that consistently contributes to the promotion of investment in pharmaceutical research and development, to the mutual advantage of innovators and patients, in a manner conducive to the social and economic welfare of Canadians.
Fan, Saijun; Ma, Yong Xian; Gao, Min; Yuan, Ren-Qi; Meng, Qinghui; Goldberg, Itzhak D.; Rosen, Eliot M.
2001-01-01
Hepatocyte growth factor (scatter factor) (HGF/SF) is a pleiotrophic mediator of epithelial cell motility, morphogenesis, angiogenesis, and tumorigenesis. HGF/SF protects cells against DNA damage by a pathway from its receptor c-Met to phosphatidylinositol 3-kinase (PI3K) to c-Akt, resulting in enhanced DNA repair and decreased apoptosis. We now show that protection against the DNA-damaging agent adriamycin (ADR; topoisomerase IIα inhibitor) requires the Grb2-binding site of c-Met, and overexpression of the Grb2-associated binder Gab1 (a multisubstrate adapter required for epithelial morphogenesis) inhibits the ability of HGF/SF to protect MDCK epithelial cells against ADR. In contrast to Gab1 and its homolog Gab2, overexpression of c-Cb1, another multisubstrate adapter that associates with c-Met, did not affect protection. Gab1 blocked the ability of HGF/SF to cause the sustained activation of c-Akt and c-Akt signaling (FKHR phosphorylation). The Gab1 inhibition of sustained c-Akt activation and of cell protection did not require the Gab1 pleckstrin homology or SHP2 phosphatase-binding domain but did require the PI3K-binding domain. HGF/SF protection of parental MDCK cells was blocked by wortmannin, expression of PTEN, and dominant negative mutants of p85 (regulatory subunit of PI3K), Akt, and Pak1; the protection of cells overexpressing Gab1 was restored by wild-type or activated mutants of p85, Akt, and Pak1. These findings suggest that the adapter Gab1 may redirect c-Met signaling through PI3K away from a c-Akt/Pak1 cell survival pathway. PMID:11438654
Riessland, Markus; Kaczmarek, Anna; Schneider, Svenja; Swoboda, Kathryn J; Löhr, Heiko; Bradler, Cathleen; Grysko, Vanessa; Dimitriadi, Maria; Hosseinibarkooie, Seyyedmohsen; Torres-Benito, Laura; Peters, Miriam; Upadhyay, Aaradhita; Biglari, Nasim; Kröber, Sandra; Hölker, Irmgard; Garbes, Lutz; Gilissen, Christian; Hoischen, Alexander; Nürnberg, Gudrun; Nürnberg, Peter; Walter, Michael; Rigo, Frank; Bennett, C Frank; Kye, Min Jeong; Hart, Anne C; Hammerschmidt, Matthias; Kloppenburg, Peter; Wirth, Brunhilde
2017-02-02
Homozygous SMN1 loss causes spinal muscular atrophy (SMA), the most common lethal genetic childhood motor neuron disease. SMN1 encodes SMN, a ubiquitous housekeeping protein, which makes the primarily motor neuron-specific phenotype rather unexpected. SMA-affected individuals harbor low SMN expression from one to six SMN2 copies, which is insufficient to functionally compensate for SMN1 loss. However, rarely individuals with homozygous absence of SMN1 and only three to four SMN2 copies are fully asymptomatic, suggesting protection through genetic modifier(s). Previously, we identified plastin 3 (PLS3) overexpression as an SMA protective modifier in humans and showed that SMN deficit impairs endocytosis, which is rescued by elevated PLS3 levels. Here, we identify reduction of the neuronal calcium sensor Neurocalcin delta (NCALD) as a protective SMA modifier in five asymptomatic SMN1-deleted individuals carrying only four SMN2 copies. We demonstrate that NCALD is a Ca 2+ -dependent negative regulator of endocytosis, as NCALD knockdown improves endocytosis in SMA models and ameliorates pharmacologically induced endocytosis defects in zebrafish. Importantly, NCALD knockdown effectively ameliorates SMA-associated pathological defects across species, including worm, zebrafish, and mouse. In conclusion, our study identifies a previously unknown protective SMA modifier in humans, demonstrates modifier impact in three different SMA animal models, and suggests a potential combinatorial therapeutic strategy to efficiently treat SMA. Since both protective modifiers restore endocytosis, our results confirm that endocytosis is a major cellular mechanism perturbed in SMA and emphasize the power of protective modifiers for understanding disease mechanism and developing therapies. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Emotion regulation deficits in regular marijuana users.
Zimmermann, Kaeli; Walz, Christina; Derckx, Raissa T; Kendrick, Keith M; Weber, Bernd; Dore, Bruce; Ochsner, Kevin N; Hurlemann, René; Becker, Benjamin
2017-08-01
Effective regulation of negative affective states has been associated with mental health. Impaired regulation of negative affect represents a risk factor for dysfunctional coping mechanisms such as drug use and thus could contribute to the initiation and development of problematic substance use. This study investigated behavioral and neural indices of emotion regulation in regular marijuana users (n = 23) and demographically matched nonusing controls (n = 20) by means of an fMRI cognitive emotion regulation (reappraisal) paradigm. Relative to nonusing controls, marijuana users demonstrated increased neural activity in a bilateral frontal network comprising precentral, middle cingulate, and supplementary motor regions during reappraisal of negative affect (P < 0.05, FWE) and impaired emotion regulation success on the behavioral level (P < 0.05). Amygdala-focused analyses further revealed impaired amygdala downregulation in the context of decreased amygdala-dorsolateral prefrontal cortex functional connectivity (P < 0.05, FWE) during reappraisal in marijuana users relative to controls. Together, the present findings could reflect an unsuccessful attempt of compensatory recruitment of additional neural resources in the context of disrupted amygdala-prefrontal interaction during volitional emotion regulation in marijuana users. As such, impaired volitional regulation of negative affect might represent a consequence of, or risk factor for, regular marijuana use. Hum Brain Mapp 38:4270-4279, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Nonsense-Mediated Decay in Genetic Disease: Friend or Foe?
Miller, Jake N.; Pearce, David A.
2014-01-01
Eukaryotic cells utilize various RNA quality control mechanisms to ensure high fidelity of gene expression, thus protecting against the accumulation of nonfunctional RNA and the subsequent production of abnormal peptides. Messenger RNAs (mRNAs) are largely responsible for protein production, and mRNA quality control is particularly important for protecting the cell against the downstream effects of genetic mutations. Nonsense-mediated decay (NMD) is an evolutionarily conserved mRNA quality control system in all eukaryotes that degrades transcripts containing premature termination codons (PTCs). By degrading these aberrant transcripts, NMD acts to prevent the production of truncated proteins that could otherwise harm the cell through various insults, such as dominant negative effects or the ER stress response. Although NMD functions to protect the cell against the deleterious effects of aberrant mRNA, there is a growing body of evidence that mutation-, codon-, gene-, cell-, and tissue-specific differences in NMD efficiency can alter the underlying pathology of genetic disease. In addition, the protective role that NMD plays in genetic disease can undermine current therapeutic strategies aimed at increasing the production of full-length functional protein from genes harboring nonsense mutations. Here, we review the normal function of this RNA surveillance pathway and how it is regulated, provide current evidence for the role that it plays in modulating genetic disease phenotypes, and how NMD can be used as a therapeutic target. PMID:25485595
Marks, Ellen; Goggins, Bridie J; Cardona, Jocelle; Cole, Siobhan; Minahan, Kyra; Mateer, Sean; Walker, Marjorie M; Shalwitz, Robert; Keely, Simon
2015-02-01
Pharmacological induction of hypoxia-inducible factor (HIF), a global transcriptional regulator of the hypoxic response, by prolyl hydroxylase inhibitors (PHDi) is protective in murine models of colitis, and epithelial cells are critical for the observed therapeutic efficacy. Because systemic HIF activation may lead to potentially negative off-target effects, we hypothesized that targeting epithelial HIF through oral delivery of PHDi would be sufficient to protect against colitis in a mouse model. Using a chemically induced trinitrobenzene sulfonic acid murine model of colitis, we compared the efficacy of oral and intraperitoneal (i.p.) delivery of the PHDi; AKB-4924 in preventing colitis, as measured by endoscopy, histology, barrier integrity, and immune profiling. Furthermore, we measured potential off-target effects, examining HIF and HIF target genes in the heart and kidney, as well as erythropoietin and hematocrit levels. Oral administration of AKB-4924 exhibited mucosal protection comparable i.p. dosing. Oral delivery of PHDi led to reduced colonic epithelial HIF stabilization compared with i.p. delivery, but this was still sufficient to induce transcription of downstream HIF targets. Furthermore, oral delivery of PHDi led to reduced stabilization of HIF and activation of HIF targets in extraintestinal organs. Oral delivery of PHDi therapies to this intestinal mucosa protects against colitis in animal models and represents a potential therapeutic strategy for inflammatory bowel disease, which also precludes unwanted extraintestinal effects.
Labour Market Effects of Employment Protection. IAB Labour Market Research Topics.
ERIC Educational Resources Information Center
Walwei, Ulrich
The labor market effects of employment protection were examined in a study of Germany's employment protection regulations and their impact on employment practices and patterns. The following topics were considered: (1) the question of whether Germany's labor market problems are a result of regulations; (2) employment security as a subject of labor…
Federal Register 2010, 2011, 2012, 2013, 2014
2010-06-09
... Cigarettes and Smokeless Tobacco to Protect Children and Adolescents; Availability AGENCY: Food and Drug... Regulations Restricting the Sale and Distribution of Cigarettes and Smokeless Tobacco To Protect Children and... restricting the sale and distribution of cigarettes and smokeless tobacco in order to protect children and...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-20
... Fisheries Service) are issuing regulations under the Marine Mammal Protection Act to govern the... submarines. The Navy's activities are military readiness activities under the Marine Mammal Protection Act of... under the Marine Mammal Protection Act. The 2007 regulations governing take incidental to SURTASS LFA...
Pratt, Maayan; Singer, Magi; Kanat-Maymon, Yaniv; Feldman, Ruth
2015-11-01
How infants shape their own development has puzzled developmentalists for decades. Recent models suggest that infant dispositions, particularly negative reactivity and regulation, affect outcome by determining the extent of parental effects. Here, we used a microanalytic experimental approach and proposed that infants with varying levels of negative reactivity will be differentially impacted by parent-infant synchrony in predicting physiological and behavioral regulation of increasing social stress during an experimental paradigm. One hundred and twenty-two mother-infant dyads (4-6 months) were observed in the face-to-face still face (SF) paradigm and randomly assigned to three experimental conditions: SF with touch, standard SF, and SF with arms' restraint. Mother-infant synchrony and infant negative reactivity were observed at baseline, and three mechanisms of behavior regulation were microcoded; distress, disengagement, and social regulation. Respiratory sinus arrhythmia baseline, reactivity, and recovery were quantified. Structural equation modeling provided support for our hypothesis. For physiological regulation, infants high in negative reactivity receiving high mother-infant synchrony showed greater vagal withdrawal, which in turn predicted comparable levels of vagal recovery to that of nonreactive infants. In behavioral regulation, only infants low in negative reactivity who received high synchrony were able to regulate stress by employing social engagement cues during the SF phase. Distress was reduced only among calm infants to highly synchronous mothers, and disengagement was lowest among highly reactive infants experiencing high mother-infant synchrony. Findings chart two pathways by which synchrony may bolster regulation in infants of high and low reactivity. Among low reactive infants, synchrony builds a social repertoire for handling interpersonal stress, whereas in highly reactive infants, it constructs a platform for repeated reparation of momentary interactive "failures" and reduces the natural tendency of stressed infants to disengage from source of distress. Implications for the construction of synchrony-focused interventions targeting infants of varying dispositions are discussed.
Mindfulness and emotion regulation—an fMRI study
Lutz, Jacqueline; Herwig, Uwe; Opialla, Sarah; Hittmeyer, Anna; Jäncke, Lutz; Rufer, Michael; Grosse Holtforth, Martin
2014-01-01
Mindfulness—an attentive non-judgmental focus on present experiences—is increasingly incorporated in psychotherapeutic treatments as a skill fostering emotion regulation. Neurobiological mechanisms of actively induced emotion regulation are associated with prefrontally mediated down-regulation of, for instance, the amygdala. We were interested in neurobiological correlates of a short mindfulness instruction during emotional arousal. Using functional magnetic resonance imaging, we investigated effects of a short mindfulness intervention during the cued expectation and perception of negative and potentially negative pictures (50% probability) in 24 healthy individuals compared to 22 controls. The mindfulness intervention was associated with increased activations in prefrontal regions during the expectation of negative and potentially negative pictures compared to controls. During the perception of negative stimuli, reduced activation was identified in regions involved in emotion processing (amygdala, parahippocampal gyrus). Prefrontal and right insular activations when expecting negative pictures correlated negatively with trait mindfulness, suggesting that more mindful individuals required less regulatory resources to attenuate emotional arousal. Our findings suggest emotion regulatory effects of a short mindfulness intervention on a neurobiological level. PMID:23563850
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.…
Skeer, M; Siegel, M
2003-06-01
To describe the range of restaurant smoking regulations in the 351 cities and towns in Massachusetts, and to analyse the level of protection from secondhand smoke exposure guaranteed by these regulations. We obtained the local restaurant smoking regulations for each town, analysing them in terms of the protection of restaurant workers, bar workers, and adult and youth restaurant customers. The percentage of restaurant patrons and workers and bar workers who are protected from secondhand smoke exposure by the current smoking regulations in Massachusetts. As of June 2002, 225 towns had local restaurant smoking regulations. Of these, 69 (30.7%) do not allow smoking in restaurants, 10 (4.4%) restrict smoking to adult only restaurants, 64 (28.4%) restrict smoking to enclosed, separately ventilated areas, and 82 (36.4%) restrict smoking to areas that need not be enclosed and separately ventilated. Of the 174 towns that, at a minimum, restrict smoking to bar areas or separately ventilated areas, 35 (20.1%) allow variances. Overall, 60 towns, covering only 17.7% of the population, completely ban smoking in restaurants. As a result, 81.3% of adult restaurant customers, 81.2% of youth customers, 82.3% of restaurant workers, and 87.0% of bar workers are not guaranteed protection from secondhand smoke in restaurants. Despite the widespread adoption of local restaurant smoking regulations in Massachusetts, the majority of restaurant customers and workers remain unprotected from secondhand smoke exposure. In light of this, public health practitioners must stop compromising the protection of customers and workers from secondhand smoke exposure in restaurants.
Caffeine Induces the Stress Response and Up-Regulates Heat Shock Proteins in Caenorhabditis elegans.
Al-Amin, Mohammad; Kawasaki, Ichiro; Gong, Joomi; Shim, Yhong-Hee
2016-02-01
Caffeine has both positive and negative effects on physiological functions in a dose-dependent manner. C. elegans has been used as an animal model to investigate the effects of caffeine on development. Caffeine treatment at a high dose (30 mM) showed detrimental effects and caused early larval arrest. We performed a comparative proteomic analysis to investigate the mode of action of high-dose caffeine treatment in C. elegans and found that the stress response proteins, heat shock protein (HSP)-4 (endoplasmic reticulum [ER] chaperone), HSP-6 (mitochondrial chaperone), and HSP-16 (cytosolic chaperone), were induced and their expression was regulated at the transcriptional level. These findings suggest that high-dose caffeine intake causes a strong stress response and activates all three stress-response pathways in the worms, including the ER-, mitochondrial-, and cytosolic pathways. RNA interference of each hsp gene or in triple combination retarded growth. In addition, caffeine treatment stimulated a food-avoidance behavior (aversion phenotype), which was enhanced by RNAi depletion of the hsp-4 gene. Therefore, up-regulation of hsp genes after caffeine treatment appeared to be the major responses to alleviate stress and protect against developmental arrest.
The CWI Pathway: Regulation of the Transcriptional Adaptive Response to Cell Wall Stress in Yeast
Sanz, Ana Belén; García, Raúl; Rodríguez-Peña, José M.; Arroyo, Javier
2017-01-01
Fungi are surrounded by an essential structure, the cell wall, which not only confers cell shape but also protects cells from environmental stress. As a consequence, yeast cells growing under cell wall damage conditions elicit rescue mechanisms to provide maintenance of cellular integrity and fungal survival. Through transcriptional reprogramming, yeast modulate the expression of genes important for cell wall biogenesis and remodeling, metabolism and energy generation, morphogenesis, signal transduction and stress. The yeast cell wall integrity (CWI) pathway, which is very well conserved in other fungi, is the key pathway for the regulation of this adaptive response. In this review, we summarize the current knowledge of the yeast transcriptional program elicited to counterbalance cell wall stress situations, the role of the CWI pathway in the regulation of this program and the importance of the transcriptional input received by other pathways. Modulation of this adaptive response through the CWI pathway by positive and negative transcriptional feedbacks is also discussed. Since all these regulatory mechanisms are well conserved in pathogenic fungi, improving our knowledge about them will have an impact in the developing of new antifungal therapies. PMID:29371494
Binns, Nino
2009-02-01
The primary role of the extensive and complex modern food legislation is to protect the consumer. Providing a framework for industry and enabling free trade are secondary aims. In the EU the 2006 Regulation on nutrition and health claims made on foods was adopted in December 2006. This Regulation defines detailed lists of permitted claims with precise conditions, requires foods making claims to meet specific nutrient profiles and requires the submission of a dossier for approval of new health claims. Nutrient profiles and an initial list of existing health claims will not be agreed until January 2009 and January 2010 respectively. The uncertainty about profiles and the initial list of claims as well as the prescriptive nature of the Regulation will have a major impact, some negative but some positive, on food innovation. Worldwide legislation on nutrition and health claims continues to develop. The current paper also provides an outline of some other key pieces of European legislation that affect food innovation. However, currently, all this legislation remains in development and up-to-date information can be sought from the reference material provided.
Rossi, Mario; Fasciani, Irene; Marampon, Francesco; Maggio, Roberto; Scarselli, Marco
2017-06-01
D 2 and D 3 dopamine receptors belong to the largest family of cell surface proteins in eukaryotes, the G protein-coupled receptors (GPCRs). Considering their crucial physiologic functions and their relatively accessible cellular locations, GPCRs represent one of the most important classes of therapeutic targets. Until recently, the only strategy to develop drugs regulating GPCR activity was through the identification of compounds that directly acted on the orthosteric sites for endogenous ligands. However, many efforts have recently been made to identify small molecules that are able to interact with allosteric sites. These sites are less well-conserved, therefore allosteric ligands have greater selectivity on the specific receptor. Strikingly, the use of allosteric modulators can provide specific advantages, such as an increased selectivity for GPCR subunits and the ability to introduce specific beneficial therapeutic effects without disrupting the integrity of complex physiologically regulated networks. In 2010, our group unexpectedly found that N -[(1r,4r)-4-[2-(7-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-1H-indole-2-carboxamide (SB269652), a compound supposed to interact with the orthosteric binding site of dopamine receptors, was actually a negative allosteric modulator of D 2 - and D 3 -receptor dimers, thus identifying the first allosteric small molecule acting on these important therapeutic targets. This review addresses the progress in understanding the molecular mechanisms of interaction between the negative modulator SB269652 and D 2 and D 3 dopamine receptor monomers and dimers, and surveys the prospects for developing new dopamine receptor allosteric drugs with SB269652 as the leading compound. U.S. Government work not protected by U.S. copyright.
Global functional analyses of cellular responses to pore-forming toxins.
Kao, Cheng-Yuan; Los, Ferdinand C O; Huffman, Danielle L; Wachi, Shinichiro; Kloft, Nicole; Husmann, Matthias; Karabrahimi, Valbona; Schwartz, Jean-Louis; Bellier, Audrey; Ha, Christine; Sagong, Youn; Fan, Hui; Ghosh, Partho; Hsieh, Mindy; Hsu, Chih-Shen; Chen, Li; Aroian, Raffi V
2011-03-01
Here we present the first global functional analysis of cellular responses to pore-forming toxins (PFTs). PFTs are uniquely important bacterial virulence factors, comprising the single largest class of bacterial protein toxins and being important for the pathogenesis in humans of many Gram positive and Gram negative bacteria. Their mode of action is deceptively simple, poking holes in the plasma membrane of cells. The scattered studies to date of PFT-host cell interactions indicate a handful of genes are involved in cellular defenses to PFTs. How many genes are involved in cellular defenses against PFTs and how cellular defenses are coordinated are unknown. To address these questions, we performed the first genome-wide RNA interference (RNAi) screen for genes that, when knocked down, result in hypersensitivity to a PFT. This screen identifies 106 genes (∼0.5% of genome) in seven functional groups that protect Caenorhabditis elegans from PFT attack. Interactome analyses of these 106 genes suggest that two previously identified mitogen-activated protein kinase (MAPK) pathways, one (p38) studied in detail and the other (JNK) not, form a core PFT defense network. Additional microarray, real-time PCR, and functional studies reveal that the JNK MAPK pathway, but not the p38 MAPK pathway, is a key central regulator of PFT-induced transcriptional and functional responses. We find C. elegans activator protein 1 (AP-1; c-jun, c-fos) is a downstream target of the JNK-mediated PFT protection pathway, protects C. elegans against both small-pore and large-pore PFTs and protects human cells against a large-pore PFT. This in vivo RNAi genomic study of PFT responses proves that cellular commitment to PFT defenses is enormous, demonstrates the JNK MAPK pathway as a key regulator of transcriptionally-induced PFT defenses, and identifies AP-1 as the first cellular component broadly important for defense against large- and small-pore PFTs.
Estimation of Danger and Endorsement of Self-Protection Strategies: A Study of Locus of Control.
ERIC Educational Resources Information Center
Heath, Linda; And Others
Contradictory predictions concerning control over negative events exist in Walster's self-protective attribution theory which maintains that on-lookers in negative situations are apt to seek control by convincing themselves that such a situation couldn't happen to them, while Shaver's defensive attribution theory suggests that in a comparable…
Within Your Control? When Problem Solving May Be Most Helpful.
Sarfan, Laurel D; Gooch, Peter; Clerkin, Elise M
2017-08-01
Emotion regulation strategies have been conceptualized as adaptive or maladaptive, but recent evidence suggests emotion regulation outcomes may be context-dependent. The present study tested whether the adaptiveness of a putatively adaptive emotion regulation strategy-problem solving-varied across contexts of high and low controllability. The present study also tested rumination, suggested to be one of the most putatively maladaptive strategies, which was expected to be associated with negative outcomes regardless of context. Participants completed an in vivo speech task, in which they were randomly assigned to a controllable ( n = 65) or an uncontrollable ( n = 63) condition. Using moderation analyses, we tested whether controllability interacted with emotion regulation use to predict negative affect, avoidance, and perception of performance. Partially consistent with hypotheses, problem solving was associated with certain positive outcomes (i.e., reduced behavioral avoidance) in the controllable (vs. uncontrollable) condition. Consistent with predictions, rumination was associated with negative outcomes (i.e., desired avoidance, negative affect, negative perception of performance) in both conditions. Overall, findings partially support contextual models of emotion regulation, insofar as the data suggest that the effects of problem solving may be more adaptive in controllable contexts for certain outcomes, whereas rumination may be maladaptive regardless of context.
Thornback, Kristin; Muller, Robert T
2015-12-01
This study examined improvement in emotion regulation throughout Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) and the degree to which improvement in emotion regulation predicted improvement in symptoms. Traumatized children, 7-12 years (69.9% female), received TF-CBT. Data from 4 time periods were used: pre-assessment (n=107), pre-treatment (n=78), post-treatment (n=58), and 6-month follow-up (n=44). Questionnaires measured emotion regulation in the form of inhibition and dysregulation (Children's Emotion Management Scales) and lability/negativity and emotion regulation skill (Emotion Regulation Checklist), as well as child-reported (Trauma Symptom Checklist for Children) and parent-reported (Trauma Symptom Checklist for Young Children) posttraumatic stress, and internalizing and externalizing problems (Child Behaviuor Checklist). To the extent that children's dysregulation and lability/negativity improved, their parents reported fewer symptoms following therapy. Improvements in inhibition best predicted improvements in child-reported posttraumatic stress (PTS) during clinical services, but change in dysregulation and lability/negativity best predicted improvement in child-reported PTS symptoms at 6-month follow-up. Moreover, statistically significant improvements of small effect size were found following therapy, for inhibition, dysregulation, and lability/negativity, but not emotion regulation skill. These findings suggest that emotion regulation is a worthy target of intervention and that improvements in emotion regulation can be made. Suggestions for future research are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.
Urgesi, Cosimo; Mattiassi, Alan D A; Buiatti, Tania; Marini, Andrea
2016-08-01
In everyday life we need to continuously regulate our emotional responses according to their social context. Strategies of emotion regulation allow individuals to control time, intensity, nature and expression of emotional responses to environmental stimuli. The left inferior frontal gyrus (LIFG) is involved in the cognitive control of the selection of semantic content. We hypothesized that it might also be involved in the regulation of emotional feelings and expressions. We applied continuous theta burst stimulation (cTBS) over LIFG or a control site before a newly-developed ecological regulation task that required participants to produce storytelling of pictures with negative or neutral valence to either a peer (unregulated condition) or a child (regulated condition). Linguistic, expressive, and physiological responses were analyzed in order to assess the effects of LIFG-cTBS on emotion regulation. Results showed that the emotion regulation context modulated the emotional content of narrative productions, but not the physiologic orienting response or the early expressive behavior to negative stimuli. Furthermore, LIFG-cTBS disrupted the text-level structuring of negative picture storytelling and the early cardiac and muscular response to negative pictures; however, it did not affect the contextual emotional regulation of storytelling. These results may suggest that LIFG is involved in the initial detection of the affective arousal of emotional stimuli. Copyright © 2016 Elsevier Inc. All rights reserved.
Morgenthau, Ari; Beddek, Amanda; Schryvers, Anthony B.
2014-01-01
Lactoferrin binding protein B (LbpB) is a bi-lobed membrane bound lipoprotein that is part of the lactoferrin receptor complex in a variety of Gram-negative pathogens. Despite high sequence diversity among LbpBs from various strains and species, a cluster of negatively charged amino acids is invariably present in the protein’s C-terminal lobe in all species except Moraxella bovis. The function of LbpB in iron acquisition has yet to be experimentally demonstrated, whereas in vitro studies have shown that LbpB confers protection against lactoferricin, a short cationic antimicrobial peptide released from the N- terminus of lactoferrin. In this study we demonstrate that the negatively charged regions can be removed from the Neisseria meningitidis LbpB without compromising stability, and this results in the inability of LbpB to protect against the bactericidal effects of lactoferricin. The release of LbpB from the cell surface by the autotransporter NalP reduces the protection against lactoferricin in the in vitro killing assay, attributed to removal of LbpB during washing steps, but is unlikely to have a similar impact in vivo. The protective effect of the negatively charged polysaccharide capsule in the killing assay was less than the protection conferred by LbpB, suggesting that LbpB plays a major role in protection against cationic antimicrobial peptides in vivo. The selective release of LbpB by NalP has been proposed to be a mechanism for evading the adaptive immune response, by reducing the antibody binding to the cell surface, but may also provide insights into the primary function of LbpB in vivo. Although TbpB and LbpB have been shown to be major targets of the human immune response, the selective release of LbpB suggests that unlike TbpB, LbpB may not be essential for iron acquisition, but important for protection against cationic antimicrobial peptides. PMID:24465982
Villarosa, Margo C; Madson, Michael B; Zeigler-Hill, Virgil; Noble, Jeremy J; Mohn, Richard S
2014-09-01
The impact of social anxiety on negative alcohol-related behaviors among college students has been studied extensively. Drinking motives are considered the most proximal indicator of college student drinking behavior. The current study examined the mediating role of drinking motives in the relationship that social anxiety symptoms have with problematic (alcohol consumption, harmful drinking, and negative consequences) and safe (protective behavioral strategies) drinking behaviors. Participants were 532 undergraduates who completed measures of social anxiety, drinking motives, alcohol use, harmful drinking patterns, negative consequences of alcohol use, and protective behavioral strategy use. Our results show that students with higher levels of social anxiety symptoms who were drinking for enhancement motives reported more harmful drinking and negative consequences, and used fewer protective behavioral strategies. Thus, students who were drinking to increase their positive mood were participating in more problematic drinking patterns compared with students reporting fewer social anxiety symptoms. Further, conformity motives partially mediated the relationship between social anxiety symptoms and negative consequences. Thus, students with more symptoms of social anxiety who were drinking in order to be accepted by their peers were more likely than others to experience negative consequences. Clinical and research implications are discussed.
Mueller, Becky; Farmer, Charles; Jermakian, Jessica; Zuby, David
2013-11-01
Pedestrian protection evaluations have been developed to encourage vehicle front-end designs that mitigate the consequences of vehicle-to-pedestrian crashes. The European New Car Assessment Program (Euro NCAP) evaluates pedestrian head protection with impacts against vehicle hood, windshield, and A-pillars. The Global Technical Regulation No. 9 (GTR 9), being evaluated for U.S. regulation, limits head protection evaluations to impacts against vehicle hoods. The objective of this study was to compare results from pedestrian head impact testing to the real-world rates of fatal and incapacitating injuries in U.S. pedestrian crashes. Data from police reported pedestrian crashes in 14 states were used to calculate real-world fatal and in- capacitating injury rates for seven 2002-07 small cars. Rates were 2.17-4.04 per 100 pedestrians struck for fatal injuries and 10.45-15.35 for incapacitating injuries. Euro NCAP style pedestrian headform tests were conducted against windshield, A-pillar, and hoods of the study vehicles. When compared with pedestrian injury rates, the vehicles' Euro NCAP scores, ranging 5-10 points, showed strong negative correlations (-0.6) to injury rates, though none were statistically significant. Data from the headform impacts for each of the study vehicles were used to calculate that vehicle's predicted serious injury risk. The predicted risks from both the Euro NCAP and GTR 9 test zones showed high positive correlations with the pedestrian fatal and incapacitating injury rates, though few were statistically significant. Whether vehicle stiffness is evaluated on all components of vehicle front ends (Euro NCAP) or is limited to hoods (GTR 9), softer vehicle components correspond to a lower risk of fatality.
Alcohol expectancies and alcohol outcomes: effects of the use of protective behavioral strategies.
Grazioli, Véronique S; Lewis, Melissa A; Garberson, Lisa A; Fossos-Wong, Nicole; Lee, Christine M; Larimer, Mary E
2015-05-01
Alcohol expectancies (AEs) are positively associated with drinking behaviors, whereas the use of protective behavioural strategies (PBS) is negatively related to alcohol outcomes among young adults. PBS have been shown to weaken relationships between some alcohol risk factors and alcohol outcomes. This study aimed to examine longitudinally the moderating effect of PBS on the relationships between AEs and alcohol outcomes among young adults. Participants (N = 188; 61.7% female) were U.S. young adults participating in a larger longitudinal study. Measures of PBS, AEs, alcohol use, and related consequences were used from the baseline and 12-month follow-up assessments. Negative binomial hurdle models found that PBS (total score) significantly moderated the relationship between positive AEs and consequences, such that among high school seniors endorsing higher positive AEs, those using more PBS in high school reported fewer negative consequences 1 year later. PBS (Manner of Drinking) also moderated the relationship between negative AEs and alcohol use, revealing the use of PBS in high school as having a protective function against later drinking among participants with high positive AEs. Last, PBS (Serious Harm Reduction) significantly moderated the associations between positive AEs and alcohol use and between negative AEs and consequences, such that participants with higher AEs and higher PBS use in high school were at greatest risk for drinking and experiencing negative consequences later. Overall, these findings suggest that PBS use may be protective by weakening relationships between positive AEs and alcohol outcomes. Limitations and future directions are discussed.
TRIF Licenses Caspase-11-Dependent NLRP3 Inflammasome Activation by Gram-Negative Bacteria
Rathinam, Vijay A.K.; Vanaja, Sivapriya Kailasan; Waggoner, Lisa; Sokolovska, Anna; Becker, Christine; Stuart, Lynda M.; Leong, John M.; Fitzgerald, Katherine A.
2013-01-01
SUMMARY Systemic infections with Gram-negative bacteria are characterized by high mortality rates due to the “sepsis syndrome,” a widespread and uncontrolled inflammatory response. Though it is well recognized that the immune response during Gram-negative bacterial infection is initiated after the recognition of endotoxin by Toll-like receptor 4, the molecular mechanisms underlying the detrimental inflammatory response during Gram-negative bacteremia remain poorly defined. Here, we identify a TRIF pathway that licenses NLRP3 inflammasome activation by all Gram-negative bacteria. By engaging TRIF, Gram-negative bacteria activate caspase-11. TRIF activates caspase-11 via type I IFN signaling, an event that is both necessary and sufficient for caspase-11 induction and autoactivation. Caspase-11 subsequently synergizes with the assembled NLRP3 inflammasome to regulate caspase-1 activation and leads to caspase-1-independent cell death. These events occur specifically during infection with Gram-negative, but not Gram-positive, bacteria. The identification of TRIF as a regulator of caspase-11 underscores the importance of TLRs as master regulators of inflammasomes during Gram-negative bacterial infection. PMID:22819539
78 FR 666 - Treasury Inflation-Protected Securities Issued at a Premium; Bond Premium Carryforward
Federal Register 2010, 2011, 2012, 2013, 2014
2013-01-04
... regulations that provide guidance on the tax treatment of a debt instrument with a bond premium carryforward... contains final regulations that provide guidance on the tax treatment of Treasury Inflation-Protected... debt instruments. The text of the temporary regulations in this document also serves as the text of the...
77 FR 8034 - Semiannual Regulatory Agenda and Fiscal Year 2011 Regulatory Plan
Federal Register 2010, 2011, 2012, 2013, 2014
2012-02-13
... ``no'' for such fields. Because the CFPB is at an early stage of its operations, it is still in the... Financial Protection Bureau--Prerule Stage Regulation Sequence No. Title Identifier No. 492 Business Lending Data 3170-AA09 (Regulation B). Consumer Financial Protection Bureau--Proposed Rule Stage Regulation...
Riva Crugnola, Cristina; Ierardi, Elena; Ferro, Valentino; Gallucci, Marcello; Parodi, Cinzia; Astengo, Marina
While the association between anxiety and postpartum depression is well known, few studies have investigated the relationship between these two states and parenting stress. Furthermore, a number of studies have found that postpartum depression affects mother-infant emotion regulation, but there has been only one study on anxiety and emotion regulation and no studies at all on parenting stress and emotion regulation. Therefore, the primary aim of our study is to identify, in a community sample of 71 mothers, the relationship between maternal depression, anxiety, and parenting stress. The second aim is to examine the relationship between anxiety, postpartum depression, and parenting stress and mother-infant emotion regulation assessed at 3 months. Mother-infant interaction was coded with a modified version of the Infant Caregiver and Engagement Phases (ICEP) using a microanalytic approach. The Edinburgh Postnatal Depression Scale (EPDS), State-Trait Anxiety Inventory (STAI), and Parenting Stress Index-Short Form (PSI-SF) were administered to the mothers to assess depression, anxiety, and parenting stress, respectively. Analysis revealed correlations between anxiety and depression, showing that parenting stress is associated with both states. In a laboratory observation, depression was correlated with both negative maternal states and negative dyadic matches as well as infant positive/mother negative mismatches; anxiety was correlated with both negative maternal states and infant negative states as well as mismatches involving one of the partners having a negative state. Multiple regression analysis showed that anxiety is a greater predictor than depression of less adequate styles of mother-infant emotion regulation. Parenting stress was not shown to predict such regulation. © 2016 S. Karger AG, Basel.
ERIC Educational Resources Information Center
Kim-Spoon, Jungmeen; Cicchetti, Dante; Rogosch, Fred A.
2013-01-01
The longitudinal contributions of emotion regulation and emotion lability-negativity to internalizing symptomatology were examined in a low-income sample (171 maltreated and 151 nonmaltreated children, from age 7 to 10 years). Latent difference score models indicated that for both maltreated and nonmaltreated children, emotion regulation was a…
[The new law on radiation protection as a consequence of the EU safety standard of 2013].
Layer, G
2017-07-01
The transformation of a European guideline (2013/59/Euratom) from 2013 into national law requires adaptation of the national statutory regulations. This year, all areas of protection from ionizing radiation will be subject to the new radiation protection law (StrlSchG). Through this, the German X‑ray and Radiation Protection Acts will be combined to form a higher level of authority. The main parts of the StrlSchG will receive a new classification and will be organized according to the exposure scenario: radiation protection in planned exposure scenarios, radiation protection in emergency exposure scenarios, radiation protection in existing exposure scenarios, and the regulation of overall exposure scenarios. The most important or modified regulated points for radiology are concerned with early recognition, where the application of X‑ray or nuclear radiation is permitted in principle under certain conditions; the consultation of medical physics experts in all diagnostic investigative procedures involving radiation and applications for radiological intervention that are linked to high doses in the person under investigation; teleradiology, another special case of the application of X‑rays in humans that requires approval, now with the "required" technical qualification in radiation protection, formerly with the "full" technical qualification, in addition to research, the simplified approval procedure being substituted with a notification procedure.Furthermore, in contrast to previous regulations, those tasked with radiation protection can contact the regulators directly in the case of conflict, which indicates considerable reinforcement of their authority.The only dose limit that will be considerably reduced is the organ-specific equivalent dose of the eye lens, where the highest value will be reduced from 150 to 20 mSv per year in those who are exposed to radiation professionally.
Eisenberg, Nancy; Liew, Jeffrey; Pidada, Sri Untari
2005-01-01
Data regarding individual differences in children’s regulation, emotionality, quality of socioemotional functioning, and shyness were obtained from teachers and peers for 112 Indonesian 6th graders. Similar data (plus parents’ reports) also were collected when these children were in 3rd grade. For boys, regulation and low negative emotionality generally predicted positive socioemotional functioning (e.g., social skills, adjustment, prosocial tendencies and peer liking, sympathy) within and across time and across reporters, even at the follow-up when initial levels of regulation or negative emotionality were controlled. For girls, relations were obtained primarily for concurrent teacher reports, probably because girls tended to be fairly well regulated and socially competent and variability in their scores was relatively low. Shyness for both sexes tended to be associated with concurrent measures of low regulation, high negative emotionality, and low quality of social competence. PMID:15355166
Hirschler-Guttenberg, Yael; Golan, Ofer; Ostfeld-Etzion, Sharon; Feldman, Ruth
2015-05-01
Children with autism spectrum disorder (ASD) exhibit difficulties in regulating emotions and authors have called to study the specific processes underpinning emotion regulation (ER) in ASD. Yet, little observational research examined the strategies preschoolers with ASD use to regulate negative and positive emotions in the presence of their mothers and fathers. Forty preschoolers with ASD and 40 matched typically developing children and their mothers and fathers participated. Families were visited twice for identical battery of paradigms with mother or father. Parent-child interactions were coded for parent and child behaviors and children engaged in ER paradigms eliciting negative (fear) and positive (joy) emotions with each parent. ER paradigms were microcoded for negative and positive emotionality, ER strategies, and parent regulation facilitation. During free play, mothers' and fathers' sensitivity and warm discipline were comparable across groups; however, children with ASD displayed lower positive engagement and higher withdrawal. During ER paradigms, children with ASD expressed less positive emotionality overall and more negative emotionality during fear with father. Children with ASD used more simple self-regulatory strategies, particularly during fear, but expressed comparable levels of assistance seeking behavior toward mother and father in negative and positive contexts. Parents of children with ASD used less complex regulation facilitation strategies, including cognitive reappraisal and emotional reframing, and employed simple tactics, such as physical comforting to manage fear and social gaze to maintain joy. Findings describe general and parent- and emotion-specific processes of child ER and parent regulation facilitation in preschoolers with ASD. Results underscore the ability of such children to seek parental assistance during moments of high arousal and the parents' sensitive adaptation to their children's needs. Reduced positive emotionality, rather than increased negative reactivity and self-regulatory efforts, emerges as the consistent element associated with ER processes in this group. © 2014 Association for Child and Adolescent Mental Health.
JNK: bridging the insulin signaling and inflammatory pathway.
Liu, Gang; Rondinone, Cristina M
2005-10-01
Obesity and insulin resistance are strongly associated with systemic markers of inflammation and endoplasmic reticulum stress. c-Jun N-terminal kinases (JNK) are activated by inflammatory cytokines and have a key role in beta-cell apoptosis and in negative regulation of insulin signaling. JNK1-deficient mice are protected from diet-induced obesity and insulin resistance, while genetically obese mice with targeted mutations in JNK1 are leaner and have reduced insulin and blood glucose levels. These studies validate JNK as a link between inflammation and metabolic diseases and as a promising drug target. This review highlights recent advances in small-molecule inhibitors of JNK that have also been targeted for other diseases with an inflammatory component such as stroke, rheumatoid arthritis, and Alzheimer's and Parkinson's diseases.
Hillier, Amy; Cole, Brian L; Smith, Tony E; Yancey, Antronette K; Williams, Jerome D; Grier, Sonya A; McCarthy, William J
2009-12-01
Using GPS devices and digital cameras, we surveyed outdoor advertisements in Austin, Los Angeles and Philadelphia. GIS and hot spot analysis revealed that unhealthy ads were clustered around child-serving institutions in Los Angeles and Philadelphia but not in Austin. Multivariate generalized least square (GLS) regression models showed that percent black (p<0.04) was a significant positive predictor of clustering in Philadelphia and percent white (p<0.06) was a marginally significant negative predictor of clustering in Los Angeles after controlling for several land use variables. The results emphasize the importance of zoning and land use regulations to protect children from exposure to unhealthy commercial messages, particularly in neighborhoods with significant racial/ethnic minority populations.
Toward a harmonized approach to animal welfare law in Canada.
Fraser, David; Koralesky, Katherine E; Urton, Geoff
2018-03-01
Animal protection law in Canada varies across the country. Federal animal protection law exists in the Criminal Code, in regulations for the transport of animals, and in regulations for humane handling and slaughter at abattoirs that are inspected by the Canadian Food Inspection Agency. Provincial animal protection laws often include provisions that i) describe a duty of care toward animals; ii) prohibit causing or permitting animal "distress;" iii) specify exemptions from prosecution; and iv) reference various national and other standards. Inconsistencies lead to duplication of effort, create difficulty in working across jurisdictions, and may erode public trust. A more consistent approach might be achieved by i) referencing a common suite of standards in provincial statutes; ii) citing the federal transport and humane slaughter regulations in provincial regulations; iii) establishing agreements so provincial authorities may enforce federal regulations; iv) wider and more uniform adoption of enforcement tools that require people to take immediate action to protect animal welfare; v) developing new standards; and vi) national consultation to define frequently used terms.
Code of Federal Regulations, 2010 CFR
2010-04-01
... complying with Environmental Protection Agency sulfur regulations (temporary). 1.179B-1T Section 1.179B-1T... capital costs incurred in complying with Environmental Protection Agency sulfur regulations (temporary... business refiner to comply with the highway diesel fuel sulfur control requirements of the Environmental...
Code of Federal Regulations, 2014 CFR
2014-04-01
... complying with Environmental Protection Agency sulfur regulations (temporary). 1.179B-1T Section 1.179B-1T... Deduction for capital costs incurred in complying with Environmental Protection Agency sulfur regulations... small business refiner to comply with the highway diesel fuel sulfur control requirements of the...
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. Copyright © 2011 Elsevier Inc. All rights reserved.
Karatzias, Thanos; Shevlin, Mark; Hyland, Philip; Brewin, Chris R; Cloitre, Marylene; Bradley, Aoife; Kitchiner, Neil J; Jumbe, Sandra; Bisson, Jonathan I; Roberts, Neil P
2018-06-01
We set out to investigate the association between negative trauma-related cognitions, emotional regulation strategies, and attachment style and complex post-traumatic stress disorder (CPTSD). As the evidence regarding the treatment of CPTSD is emerging, investigating psychological factors that are associated with CPTSD can inform the adaptation or the development of effective interventions for CPTSD. A cross-sectional design was employed. Measures of CPTSD, negative trauma-related cognitions, emotion regulation strategies, and attachment style were completed by a British clinical sample of trauma-exposed patients (N = 171). Logistic regression analysis was used to assess the predictive utility of these psychological factors on diagnosis of CPTSD as compared to PTSD. It was found that the most important factor in the diagnosis of CPTSD was negative trauma-related cognitions about the self, followed by attachment anxiety, and expressive suppression. Targeting negative thoughts and attachment representations while promoting skills acquisition in emotional regulation hold promise in the treatment of CPTSD. Further research is required on the development of appropriate models to treat CPTSD that tackle skills deficit in these areas. Results suggest that cognitive-behavioural interventions might be useful for the treatment of CPTSD. Targeting negative thoughts and attachment representations while promoting skills acquisition in emotional regulation hold promise in the treatment of CPTSD. © 2018 The British Psychological Society.
Ali, Sideeka; Alea, Nicole
2017-07-01
This study experimentally examined the affective and social consequences of emotion regulation in men and women from young adulthood to old age. Participants were instructed to reappraise, suppress, or given no instructions while recalling a negative memory about their romantic relationship. Participants were 191 adults in a Trinidadian lifespan sample. Engaging in suppression resulted in higher relationship satisfaction, particularly for women, whereas engaging in reappraisal reduced negative affect for middle-aged versus younger adults. Reappraisal was, however, particularly consequential for young women who experienced higher levels of negative affect compared with men of the same age and older aged women. Regardless of instructions, older adults experienced higher relationship satisfaction, higher positive and lower negative affect than younger aged adults. Results are discussed considering the positivity effect for older adults, and how the current and historical climate of Trinidad influences the way women regulate their emotions.
TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling
Jin, Jin; Xiao, Yichuan; Chang, Jae-Hoon; Yu, Jiayi; Hu, Hongbo; Starr, Robyn; Brittain, George C.; Chang, Mikyoung; Cheng, Xuhong; Sun, Shao-Cong
2012-01-01
Immunoglobulin (Ig) class switching is crucial for generating antibody diversity in humoral immunity and, if deregulated, also has severe pathological consequences. How the magnitude of Ig isotype switching is controlled is still poorly understood. Here we identify TANK-binding kinase 1 (TBK1) as a pivotal negative regulator of IgA class switching. B cell-specific TBK1 ablation in mice resulted in uncontrolled production of IgA and development of nephropathy-like disease symptoms. TBK1 negatively regulated IgA class switching by attenuating noncanonical NF-κB signaling, an action that involved TBK1-mediated phosphorylation and subsequent degradation of the NF-κB-inducing kinase. These findings establish TBK1 as a pivotal negative regulator of the noncanonical NF-κB pathway and highlight a unique mechanism that controls IgA production. PMID:23023393
Nestle, U; Berlich, J
2006-05-01
In 2001 or 2002, the legislator made substantial alterations to the "Röntgenverordnung" [regulations governing use of roentgen ray radiation] and "Strahlenschutzverordnung" [regulations governing radiation protection]. This was done to bring German law in line with EU Directives 96/29/Euratom (basic safety standards for the protection of the health of workers and the general public against the dangers arising from ionizing radiation) and 97/43/Euratom (health protection of individuals against the dangers of ionizing radiation in relation to medical exposure). Proper use of radiation in medicine requires that those involved in its application are aware of the biological effects of radiation. When staff and others are protected good organization and appropriate technology at the workplace can achieve a great deal. In the new directives, the radiation protection for the patient is quantified and the responsibility of the physician is clearly pointed out. The most important aim is uniform quality throughout Europe in radiological diagnosis and radiation protection.
Nestle, U; Berlich, J
2006-08-01
In 2001 or 2002, the legislator made substantial alterations to the "Röntgenverordnung" [regulations governing use of roentgen ray radiation] and "Strahlenschutzverordnung" [regulations governing radiation protection]. This was done to bring German law in line with EU Directives 96/29/Euratom (basic safety standards for the protection of the health of workers and the general public against the dangers arising from ionizing radiation) and 97/43/Euratom (health protection of individuals against the dangers of ionizing radiation in relation to medical exposure). Proper use of radiation in medicine requires that those involved in its application are aware of the biological effect of radiation. When staff and others are protected good organization and appropriate technology at the workplace can achieve a great deal. In the new directives, the radiation protection for the patient is quantified and the responsibility of the physician is clearly pointed out. The most important aim is uniform quality throughout Europe in radiological diagnosis and radiation protection.
Thickening the Global SOF Network
2013-12-01
in thought, and regulate both positive and negative emotions in oneself and others. EI is a necessary, but not fully sufficient, quality Green...assimilate emotions in thought, and regulate both positive and negative emotions in oneself and others. EI is a necessary, but not fully sufficient...both positive and negative emotions in oneself and others. B. THE HISTORY AND CONTROVERSY SURROUNDING EMOTIONAL INTELLIGENCE Since its first
ERIC Educational Resources Information Center
Kim, Sanghag; Kochanska, Grazyna
2012-01-01
This study examined infants' negative emotionality as moderating the effect of parent-child mutually responsive orientation (MRO) on children's self-regulation (n = 102). Negative emotionality was observed in anger-eliciting episodes and in interactions with parents at 7 months. MRO was coded in naturalistic interactions at 15 months.…
Caffeine alters emotion and emotional responses in low habitual caffeine consumers.
Giles, Grace E; Spring, Alexander M; Urry, Heather L; Moran, Joseph M; Mahoney, Caroline R; Kanarek, Robin B
2018-02-01
Caffeine reliably increases emotional arousal, but it is unclear whether and how it influences other dimensions of emotion such as emotional valence. These experiments documented whether caffeine influences emotion and emotion regulation choice and success. Low to abstinent caffeine consumers (maximum 100 mg/day) completed measures of state anxiety, positive and negative emotion, and salivary cortisol before, 45 min after, and 75 min after consuming 400 mg caffeine or placebo. Participants also completed an emotion regulation choice task, in which they chose to employ cognitive reappraisal or distraction in response to high and low intensity negative pictures (Experiment 1), or a cognitive reappraisal task, in which they employed cognitive reappraisal or no emotion regulation strategy in response to negative and neutral pictures (Experiment 2). State anxiety, negative emotion, and salivary cortisol were heightened both 45 and 75 min after caffeine intake relative to placebo. In Experiment 1, caffeine did not influence the frequency with which participants chose reappraisal or distraction, but reduced negativity of the picture ratings. In Experiment 2, caffeine did not influence cognitive reappraisal success. Thus, caffeine mitigated emotional responses to negative situations, but not how participants chose to regulate such responses or the success with which they did so.
Wang, Ruisi; Ding, Qian; Yaqoob, Usman; de Assuncao, Thiago M.; Verma, Vikas K.; Hirsova, Petra; Cao, Sheng; Mukhopadhyay, Debabrata; Huebert, Robert C.; Shah, Vijay H.
2015-01-01
Exosomes are cell-derived extracellular vesicles thought to promote intercellular communication by delivering specific content to target cells. The aim of this study was to determine whether endothelial cell (EC)-derived exosomes could regulate the phenotype of hepatic stellate cells (HSCs). Initial microarray studies showed that fibroblast growth factor 2 induced a 2.4-fold increase in mRNA levels of sphingosine kinase 1 (SK1). Exosomes derived from an SK1-overexpressing EC line increased HSC migration 3.2-fold. Migration was not conferred by the dominant negative SK1 exosome. Incubation of HSCs with exosomes was also associated with an 8.3-fold increase in phosphorylation of AKT and 2.5-fold increase in migration. Exosomes were found to express the matrix protein and integrin ligand fibronectin (FN) by Western blot analysis and transmission electron microscopy. Blockade of the FN-integrin interaction with a CD29 neutralizing antibody or the RGD peptide attenuated exosome-induced HSC AKT phosphorylation and migration. Inhibition of endocytosis with transfection of dynamin siRNA, the dominant negative dynamin GTPase construct Dyn2K44A, or the pharmacological inhibitor Dynasore significantly attenuated exosome-induced AKT phosphorylation. SK1 levels were increased in serum exosomes derived from mice with experimental liver fibrosis, and SK1 mRNA levels were up-regulated 2.5-fold in human liver cirrhosis patient samples. Finally, S1PR2 inhibition protected mice from CCl4-induced liver fibrosis. Therefore, EC-derived SK1-containing exosomes regulate HSC signaling and migration through FN-integrin-dependent exosome adherence and dynamin-dependent exosome internalization. These findings advance our understanding of EC/HSC cross-talk and identify exosomes as a potential target to attenuate pathobiology signals. PMID:26534962
Wang, Ruisi; Ding, Qian; Yaqoob, Usman; de Assuncao, Thiago M; Verma, Vikas K; Hirsova, Petra; Cao, Sheng; Mukhopadhyay, Debabrata; Huebert, Robert C; Shah, Vijay H
2015-12-25
Exosomes are cell-derived extracellular vesicles thought to promote intercellular communication by delivering specific content to target cells. The aim of this study was to determine whether endothelial cell (EC)-derived exosomes could regulate the phenotype of hepatic stellate cells (HSCs). Initial microarray studies showed that fibroblast growth factor 2 induced a 2.4-fold increase in mRNA levels of sphingosine kinase 1 (SK1). Exosomes derived from an SK1-overexpressing EC line increased HSC migration 3.2-fold. Migration was not conferred by the dominant negative SK1 exosome. Incubation of HSCs with exosomes was also associated with an 8.3-fold increase in phosphorylation of AKT and 2.5-fold increase in migration. Exosomes were found to express the matrix protein and integrin ligand fibronectin (FN) by Western blot analysis and transmission electron microscopy. Blockade of the FN-integrin interaction with a CD29 neutralizing antibody or the RGD peptide attenuated exosome-induced HSC AKT phosphorylation and migration. Inhibition of endocytosis with transfection of dynamin siRNA, the dominant negative dynamin GTPase construct Dyn2K44A, or the pharmacological inhibitor Dynasore significantly attenuated exosome-induced AKT phosphorylation. SK1 levels were increased in serum exosomes derived from mice with experimental liver fibrosis, and SK1 mRNA levels were up-regulated 2.5-fold in human liver cirrhosis patient samples. Finally, S1PR2 inhibition protected mice from CCl4-induced liver fibrosis. Therefore, EC-derived SK1-containing exosomes regulate HSC signaling and migration through FN-integrin-dependent exosome adherence and dynamin-dependent exosome internalization. These findings advance our understanding of EC/HSC cross-talk and identify exosomes as a potential target to attenuate pathobiology signals. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Murray-Stewart, T; Sierra, J C; Piazuelo, M B; Mera, R M; Chaturvedi, R; Bravo, L E; Correa, P; Schneider, B G; Wilson, K T; Casero, R A
2016-10-20
Chronic inflammation contributes to the development of various forms of cancer. The polyamine catabolic enzyme spermine oxidase (SMOX) is induced in chronic inflammatory conditions, including Helicobacter pylori-associated gastritis, where its production of hydrogen peroxide contributes to DNA damage and subsequent tumorigenesis. MicroRNA expression levels are also altered in inflammatory conditions; specifically, the tumor suppressor miR-124 becomes silenced by DNA methylation. We sought to determine if this repression of miR-124 is associated with elevated SMOX activity and concluded that miR-124 is indeed a negative regulator of SMOX. In gastric adenocarcinoma cells harboring highly methylated and silenced mir-124 gene loci, 5-azacytidine treatment allowed miR-124 re-expression and decreased SMOX expression. Overexpression of an exogenous miR-124-3p mimic repressed SMOX mRNA and protein expression as well as H 2 O 2 production by >50% within 24 h. Reporter assays indicated that direct interaction of miR-124 with the 3'-untranslated region of SMOX mRNA contributes to this negative regulation. Importantly, overexpression of miR-124 before infection with H. pylori prevented the induction of SMOX believed to contribute to inflammation-associated tumorigenesis. Compelling human in vivo data from H. pylori-positive gastritis tissues indicated that the mir-124 gene loci are more heavily methylated in a Colombian population characterized by elevated SMOX expression and a high risk for gastric cancer. Furthermore, the degree of mir-124 methylation significantly correlated with SMOX expression throughout the population. These results indicate a protective role for miR-124 through the inhibition of SMOX-mediated DNA damage in the etiology of H. pylori-associated gastric cancer.
Murray-Stewart, Tracy; Sierra, Johanna C.; Piazuelo, M. Blanca; Mera, Robertino M.; Chaturvedi, Rupesh; Bravo, Luis E.; Correa, Pelayo; Schneider, Barbara G.; Wilson, Keith T.; Casero, Robert A.
2016-01-01
Chronic inflammation contributes to the development of various forms of cancer. The polyamine catabolic enzyme spermine oxidase (SMOX) is induced in chronic inflammatory conditions, including Helicobacter pylori-associated gastritis, where its production of hydrogen peroxide contributes to DNA damage and subsequent tumorigenesis. MicroRNA expression levels are also altered in inflammatory conditions; specifically, the tumor suppressor miR-124 becomes silenced by DNA methylation. We sought to determine if this repression of miR-124 is associated with elevated SMOX activity and concluded that miR-124 is indeed a negative regulator of SMOX. In gastric adenocarcinoma cells harboring highly methylated and silenced mir-124 gene loci, 5-azacytidine treatment allowed miR-124 re-expression and decreased SMOX expression. Overexpression of an exogenous miR-124-3p mimic repressed SMOX mRNA and protein expression as well as H2O2 production by >50% within 24 hours. Reporter assays indicated that direct interaction of miR-124 with the 3′-untranslated region of SMOX mRNA contributes to this negative regulation. Importantly, overexpression of miR-124 prior to infection with H. pylori prevented the induction of SMOX believed to contribute to inflammation-associated tumorigenesis. Compelling human in vivo data from H. pylori-positive gastritis tissues indicated that the mir-124 gene loci are more heavily methylated in a Colombian population characterized by elevated SMOX expression and a high risk for gastric cancer. Furthermore, the degree of mir-124 methylation significantly correlated with SMOX expression throughout the population. These results indicate a protective role for miR-124 through the inhibition of SMOX-mediated DNA damage in the etiology of H. pylori-associated gastric cancer. PMID:27041578
Jo, Sungsin; Lee, Young Lim; Kim, Sojin; Lee, Hongki; Chung, Heekyoung
2016-07-01
Arsenic trioxide (ATO) is a therapeutic agent for acute promyelocytic leukemia (APL) which induces PML-RARA protein degradation via enhanced UBE2I-mediated sumoylation. PCGF2, a Polycomb group protein, has been suggested as an anti-SUMO E3 protein by inhibiting the sumoylation of UBE2I substrates, HSF2 and RANGAP1, via direct interaction. Thus, we hypothesized that PCGF2 might play a role in ATO-induced PML-RARA degradation by interacting with UBE2I. PCGF2 protein was down-regulated upon ATO treatment in human APL cell line, NB4. Knockdown of PCGF2 in NB4 cells, in the absence of ATO treatment, was sufficient to induce sumoylation-, ubiquitylation- and PML nuclear body-mediated degradation of PML-RARA protein. Moreover, overexpression of PCGF2 protected ATO-mediated degradation of ectopic and endogenous PML-RARA in 293T and NB4 cells, respectively. In 293T cells, UBE2I-mediated PML-RARA degradation was reduced upon PCGF2 co-expression. In addition, UBE2I-mediated sumoylation of PML-RARA was reduced upon PCGF2 co-expression and PCGF2-UBE2I interaction was confirmed by co-immunoprecipitation. Likewise, endogenous PCGF2-UBE2I interaction was detected by co-immunoprecipitation and immunofluorescence assays in NB4 cells. Intriguingly, upon ATO-treatment, such interaction was disrupted and UBE2I was co-immunoprecipitated or co-localized with its SUMO substrate, PML-RARA. Taken together, our results suggested a novel role of PCGF2 in ATO-mediated degradation of PML-RARA that PCGF2 might act as a negative regulator of UBE2I via direct interaction. Copyright © 2016 Elsevier B.V. All rights reserved.
Sheehan, Rachel B.; Herring, Matthew P.; Campbell, Mark J.
2018-01-01
Motivation has been the subject of much research in the sport psychology literature, whereas athlete mental health has received limited attention. Motivational complexities in elite sport are somewhat reflected in the mental health literature, where there is evidence for both protective and risk factors for athletes. Notably, few studies have linked motivation to mental health. Therefore, the key objective of this study was to test four mental health outcomes in the motivational sequence posited by the Hierarchical Model of Intrinsic and Extrinsic Motivation: motivational climate → basic psychological needs → motivation → mental health outcomes. Elite team-sport athletes (140 females, 75 males) completed seven psychometric inventories of motivation-related and mental health variables. Overall, the athletes reported positive motivational patterns, with autonomous motivation and task climate being more prevalent than their less adaptive counterparts. Elevated depressive symptoms and poor sleep quality affected nearly half of the cohort. Structural equation modeling supported pathways between motivational climate, basic needs, motivation, and mood, depressive symptoms, sleep quality, and trait anxiety. Specifically, a task climate was positively associated with the three basic psychological needs, and an ego climate was positively associated with competence. Autonomy and relatedness had positive and negative associations with autonomous and controlled forms of motivation, respectively. Controlled motivation regulations were positively associated with the four mental health outcomes. Integrated regulation had a negative association with anxiety, and intrinsic regulation had a positive association with depressive symptoms. These findings highlight the complexities of and interrelations between motivation and mental health among athletes, and support the importance of considering mental health as an outcome of motivation. PMID:29867672
Klaver, Elsenoor J.; Kuijk, Loes M.; Lindhorst, Thisbe K.; Cummings, Richard D.; van Die, Irma
2015-01-01
Schistosomiasis is a common debilitating human parasitic disease in (sub)tropical areas, however, schistosome infections can also protect against a variety of inflammatory diseases. This has raised broad interest in the mechanisms by which Schistosoma modulate the immune system into an anti-inflammatory and regulatory state. Human dendritic cells (DCs) show many phenotypic changes upon contact with Schistosoma mansoni soluble egg antigens (SEA). We here show that oxidation of SEA glycans, but not heat-denaturation, abrogates the capacity of SEA to suppress both LPS-induced cytokine secretion and DC proliferation, indicating an important role of SEA glycans in these processes. Remarkably, interaction of SEA glycans with DCs results in a strongly increased expression of Suppressor Of Cytokine Signalling1 (SOCS1) and SH2-containing protein tyrosine Phosphatase-1 (SHP1), important negative regulators of TLR4 signalling. In addition, SEA induces the secretion of transforming growth factor β (TGF-β), and the surface expression of the costimulatory molecules Programmed Death Ligand-1 (PD-L1) and OX40 ligand (OX40L), which are known phenotypic markers for the capacity of DCs to polarize naïve T cells into Th2/Treg cell subsets. Inhibition of mannose receptor (MR)-mediated internalization of SEA into DCs by blocking with allyl α-D-mannoside or anti-MR antibodies, significantly reduced SOCS1 and SHP1 expression. In conclusion, we demonstrate that SEA glycans are essential for induction of enhanced SOCS1 and SHP1 levels in DCs via the MR. Our data provide novel mechanistic evidence for the potential of S. mansoni SEA glycans to modulate human DCs, which may contribute to the capacity of SEA to down-regulate inflammatory responses. PMID:25897665
Klaver, Elsenoor J; Kuijk, Loes M; Lindhorst, Thisbe K; Cummings, Richard D; van Die, Irma
2015-01-01
Schistosomiasis is a common debilitating human parasitic disease in (sub)tropical areas, however, schistosome infections can also protect against a variety of inflammatory diseases. This has raised broad interest in the mechanisms by which Schistosoma modulate the immune system into an anti-inflammatory and regulatory state. Human dendritic cells (DCs) show many phenotypic changes upon contact with Schistosoma mansoni soluble egg antigens (SEA). We here show that oxidation of SEA glycans, but not heat-denaturation, abrogates the capacity of SEA to suppress both LPS-induced cytokine secretion and DC proliferation, indicating an important role of SEA glycans in these processes. Remarkably, interaction of SEA glycans with DCs results in a strongly increased expression of Suppressor Of Cytokine Signalling1 (SOCS1) and SH2-containing protein tyrosine Phosphatase-1 (SHP1), important negative regulators of TLR4 signalling. In addition, SEA induces the secretion of transforming growth factor β (TGF-β), and the surface expression of the costimulatory molecules Programmed Death Ligand-1 (PD-L1) and OX40 ligand (OX40L), which are known phenotypic markers for the capacity of DCs to polarize naïve T cells into Th2/Treg cell subsets. Inhibition of mannose receptor (MR)-mediated internalization of SEA into DCs by blocking with allyl α-D-mannoside or anti-MR antibodies, significantly reduced SOCS1 and SHP1 expression. In conclusion, we demonstrate that SEA glycans are essential for induction of enhanced SOCS1 and SHP1 levels in DCs via the MR. Our data provide novel mechanistic evidence for the potential of S. mansoni SEA glycans to modulate human DCs, which may contribute to the capacity of SEA to down-regulate inflammatory responses.
Lukavská, Kateřina; Hrabec, Ondřej; Chrz, Vladimír
2016-04-01
We examined the effect of habitual regulation of massive multiplayer online role-playing game (MMORPG) playing on the problematic (addictive) usage and excessiveness of gaming (time that user spent playing weekly, per session, and in relation to his other leisure activities). We developed the approach to assess the strength of habitual regulation that was based on sensitivity to situational cues. We defined cues as real-life or in-game conditions (e.g., work to be done, activities with friends or family, need to relax, new game expansion) that usually promote gaming (proplay cues) or prevent it (contraplay cues). Using a sample of 377 MMORPG players, we analyzed relationships between variables through partial least squares path modeling. We found that proplay cues sensitivity significantly positively affected the excessiveness of gaming (playing time) as well as the occurrence of problematic usage symptoms. Conversely, contraplay cues sensitivity functioned as a protective factor from these conditions; significant negative effects were found for playing time and problematic usage. Playing time was confirmed to be a mediating variable, affected by cues sensitivity and at the same time affecting problematic usage symptoms. We obtained moderately strong coefficients of determination for both endogenous variables (R(2) = 0.28 for playing time; R(2) = 0.31 for problematic usage) suggesting that the proposed variables possess good explanatory power. Based on our results, we argue that the strength of habitual regulation within MMORPG usage has both positive and negative effects on excessive and problematic usage, which is a new and important finding within the area of Internet gaming addiction.
Comprehensive Logic Based Analyses of Toll-Like Receptor 4 Signal Transduction Pathway
Padwal, Mahesh Kumar; Sarma, Uddipan; Saha, Bhaskar
2014-01-01
Among the 13 TLRs in the vertebrate systems, only TLR4 utilizes both Myeloid differentiation factor 88 (MyD88) and Toll/Interleukin-1 receptor (TIR)-domain-containing adapter interferon-β-inducing Factor (TRIF) adaptors to transduce signals triggering host-protective immune responses. Earlier studies on the pathway combined various experimental data in the form of one comprehensive map of TLR signaling. But in the absence of adequate kinetic parameters quantitative mathematical models that reveal emerging systems level properties and dynamic inter-regulation among the kinases/phosphatases of the TLR4 network are not yet available. So, here we used reaction stoichiometry-based and parameter independent logical modeling formalism to build the TLR4 signaling network model that captured the feedback regulations, interdependencies between signaling kinases and phosphatases and the outcome of simulated infections. The analyses of the TLR4 signaling network revealed 360 feedback loops, 157 negative and 203 positive; of which, 334 loops had the phosphatase PP1 as an essential component. The network elements' interdependency (positive or negative dependencies) in perturbation conditions such as the phosphatase knockout conditions revealed interdependencies between the dual-specific phosphatases MKP-1 and MKP-3 and the kinases in MAPK modules and the role of PP2A in the auto-regulation of Calmodulin kinase-II. Our simulations under the specific kinase or phosphatase gene-deficiency or inhibition conditions corroborated with several previously reported experimental data. The simulations to mimic Yersinia pestis and E. coli infections identified the key perturbation in the network and potential drug targets. Thus, our analyses of TLR4 signaling highlights the role of phosphatases as key regulatory factors in determining the global interdependencies among the network elements; uncovers novel signaling connections; identifies potential drug targets for infections. PMID:24699232
Xu, Qian; Liu, Wei; Liu, Xiaoling; Liu, Weiwei; Wang, Hongju; Yao, Guodong; Zang, Linghe; Hayashi, Toshihiko; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi
2016-09-01
Primary cilium is a cellular antenna, signalling as a sensory organelle. Numerous pathological manifestation is associated with change of its length. Although the interaction between autophagy and primary cilia has been suggested, the role of autophagy in primary cilia length is largely unknown. In this study the primary cilia were immunostained and observed by using confocal fluorescence microscopy, and we found that silibinin, a natural flavonoid, shortened the length of primary cilia, meanwhile it also induced autophagy in 3T3-L1 cells. This study was designed to investigate the significance of silibinin-induced autophagy in primary ciliary structure in confluent mouse embryo fibroblast 3T3-L1 cells. Either blocking the autophagic flux with pre-treatment with the autophagy inhibitor, 3-methyladenine (3-MA), or transfection of siRNA targeting LC3 inhibited the reduction of cilia length caused by silibinin exposure. Autophagy induced by silibinin decreased expressions of the cilia-associated proteins, such as IFT88, KIF3a and Ac-tubulin, while 3-MA restored it, indicating that autophagy induced by silibinin led to a reduction of primary cilia length. Histone deacetylase 6 (HDAC6), which was suggested as a mediator of autophagy, was up-regulated by silibinin in a time-dependent manner. In addition, 3T3-L1 cells treated with siRNA against HDAC6 had a reduced autophagic level and were protected from silibinin-induced cilia shortening. Taken together, we conclude that the HDAC6-mediated autophagy negatively regulates primary cilia length during silibinin treatment and has the potential to serve as a therapeutic target for primary cilia-associated ciliopathies. These findings thus provide new information about the potential link between autophagy and primary cilia.
Sheehan, Rachel B; Herring, Matthew P; Campbell, Mark J
2018-01-01
Motivation has been the subject of much research in the sport psychology literature, whereas athlete mental health has received limited attention. Motivational complexities in elite sport are somewhat reflected in the mental health literature, where there is evidence for both protective and risk factors for athletes. Notably, few studies have linked motivation to mental health. Therefore, the key objective of this study was to test four mental health outcomes in the motivational sequence posited by the Hierarchical Model of Intrinsic and Extrinsic Motivation: motivational climate → basic psychological needs → motivation → mental health outcomes. Elite team-sport athletes (140 females, 75 males) completed seven psychometric inventories of motivation-related and mental health variables. Overall, the athletes reported positive motivational patterns, with autonomous motivation and task climate being more prevalent than their less adaptive counterparts. Elevated depressive symptoms and poor sleep quality affected nearly half of the cohort. Structural equation modeling supported pathways between motivational climate, basic needs, motivation, and mood, depressive symptoms, sleep quality, and trait anxiety. Specifically, a task climate was positively associated with the three basic psychological needs, and an ego climate was positively associated with competence. Autonomy and relatedness had positive and negative associations with autonomous and controlled forms of motivation, respectively. Controlled motivation regulations were positively associated with the four mental health outcomes. Integrated regulation had a negative association with anxiety, and intrinsic regulation had a positive association with depressive symptoms. These findings highlight the complexities of and interrelations between motivation and mental health among athletes, and support the importance of considering mental health as an outcome of motivation.
MDM2 controls NRF2 antioxidant activity in prevention of diabetic kidney disease.
Guo, Weiying; Tian, Dan; Jia, Ye; Huang, Wenlin; Jiang, Mengnan; Wang, Junnan; Sun, Weixia; Wu, Hao
2018-04-26
Oxidative stress and P53 contribute to the pathogenesis of diabetic kidney disease (DKD). Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular antioxidant defense system, is negatively regulated by P53 and prevents DKD. Recent findings revealed an important role of mouse double minute 2 (MDM2) in protection against DKD. However, the mechanism remained unclear. We hypothesized that MDM2 enhances NRF2 antioxidant signaling in DKD given that MDM2 is a key negative regulator of P53. The MDM2 inhibitor nutlin3a elevated renal P53, inhibited NRF2 signaling and induced oxidative stress, inflammation, fibrosis, DKD-like renal pathology and albuminuria in the wild-type (WT) non-diabetic mice. These effects exhibited more prominently in nutlin3a-treated WT diabetic mice. Interestingly, nutlin3a failed to induce greater renal injuries in the Nrf2 knockout (KO) mice under both the diabetic and non-diabetic conditions, indicating that NRF2 predominantly mediates MDM2's action. On the contrary, P53 inhibition by pifithrin-α activated renal NRF2 signaling and the expression of Mdm2, and attenuated DKD in the WT diabetic mice, but not in the Nrf2 KO diabetic mice. In high glucose-treated mouse mesangial cells, P53 gene silencing completely abolished nutlin3a's inhibitory effect on NRF2 signaling. The present study demonstrates for the first time that MDM2 controls renal NRF2 antioxidant activity in DKD via inhibition of P53, providing MDM2 activation and P53 inhibition as novel strategies in the management of DKD. Copyright © 2018 Elsevier B.V. All rights reserved.
Goldin, Philippe R.; Manber, Tali; Hakimi, Shabnam; Canli, Turhan; Gross, James J.
2014-01-01
Context Social anxiety disorder is thought to involve emotional hyper-reactivity, cognitive distortions, and ineffective emotion regulation. While the neural bases of emotional reactivity to social stimuli have been described, the neural bases of emotional reactivity and cognitive regulation during social and physical threat, and their relationship to social anxiety symptom severity, have yet to be investigated. Objective This study investigated behavioral and neural correlates of emotional reactivity and cognitive regulation in patients and controls during processing of social and physical threat stimuli. Design Participants were trained to implement cognitive-linguistic regulation of emotional reactivity induced by social (harsh facial expressions) and physical (violent scenes) threat while undergoing functional magnetic resonance imaging and providing behavioral ratings of negative emotion experience. Setting Academic psychology department. Participants 15 adults with social anxiety disorder and 17 demographically-matched healthy controls. Main Outcome Measures Blood oxygen level dependent signal and negative emotion ratings. Results Behaviorally, patients reported greater negative emotion than controls during social and physical threat, but showed equivalent reduction in negative emotion following cognitive regulation. Neurally, viewing social threat resulted in greater emotion-related neural responses in patients than controls, with social anxiety symptom severity related to activity in a network of emotion and attention processing regions in patients only. Viewing physical threat produced no between-group differences. Regulation during social threat resulted in greater cognitive and attention regulation-related brain activation in controls compared to patients. Regulation during physical threat produced greater cognitive control-related response (i.e., right DLPFC) in patients compared to controls. Conclusions Compared to controls, patients demonstrated exaggerated negative emotion reactivity and reduced cognitive regulation related neural activation, specifically for social threat stimuli. These findings help to elucidate potential neural mechanisms of emotion regulation that might serve as biomarkers for interventions for social anxiety disorder. PMID:19188539
Cheng, Fang; Cheng, Zhihui
2015-01-01
Allelopathy is a common biological phenomenon by which one organism produces biochemicals that influence the growth, survival, development, and reproduction of other organisms. These biochemicals are known as allelochemicals and have beneficial or detrimental effects on target organisms. Plant allelopathy is one of the modes of interaction between receptor and donor plants and may exert either positive effects (e.g., for agricultural management, such as weed control, crop protection, or crop re-establishment) or negative effects (e.g., autotoxicity, soil sickness, or biological invasion). To ensure sustainable agricultural development, it is important to exploit cultivation systems that take advantage of the stimulatory/inhibitory influence of allelopathic plants to regulate plant growth and development and to avoid allelopathic autotoxicity. Allelochemicals can potentially be used as growth regulators, herbicides, insecticides, and antimicrobial crop protection products. Here, we reviewed the plant allelopathy management practices applied in agriculture and the underlying allelopathic mechanisms described in the literature. The major points addressed are as follows: (1) Description of management practices related to allelopathy and allelochemicals in agriculture. (2) Discussion of the progress regarding the mode of action of allelochemicals and the physiological mechanisms of allelopathy, consisting of the influence on cell micro- and ultra-structure, cell division and elongation, membrane permeability, oxidative and antioxidant systems, growth regulation systems, respiration, enzyme synthesis and metabolism, photosynthesis, mineral ion uptake, protein and nucleic acid synthesis. (3) Evaluation of the effect of ecological mechanisms exerted by allelopathy on microorganisms and the ecological environment. (4) Discussion of existing problems and proposal for future research directions in this field to provide a useful reference for future studies on plant allelopathy. PMID:26635845
Lashbrooke, Justin; Aharoni, Asaph; Costa, Fabrizio
2015-01-01
The outer epidermal layer of apple fruit is covered by a protective cuticle. Composed of a polymerized cutin matrix embedded with waxes, the cuticle is a natural waterproof barrier and protects against several abiotic and biotic stresses. In terms of apple production, the cuticle is essential to maintain long post-harvest storage, while severe failure of the cuticle can result in the formation of a disorder known as russet. Apple russet results from micro-cracking of the cuticle and the formation of a corky suberized layer. This is typically an undesirable consumer trait, and negatively impacts the post-harvest storage of apples. In order to identify genetic factors controlling cuticle biosynthesis (and thus preventing russet) in apple, a quantitative trait locus (QTL) mapping survey was performed on a full-sib population. Two genomic regions located on chromosomes 2 and 15 that could be associated with russeting were identified. Apples with compromised cuticles were identified through a novel and high-throughput tensile analysis of the skin, while histological analysis confirmed cuticle failure in a subset of the progeny. Additional genomic investigation of the determined QTL regions identified a set of underlying genes involved in cuticle biosynthesis. Candidate gene expression profiling by quantitative real-time PCR on a subset of the progeny highlighted the specific expression pattern of a SHN1/WIN1 transcription factor gene (termed MdSHN3) on chromosome 15. Orthologues of SHN1/WIN1 have been previously shown to regulate cuticle formation in Arabidopsis, tomato, and barley. The MdSHN3 transcription factor gene displayed extremely low expression in lines with improper cuticle formation, suggesting it to be a fundamental regulator of cuticle biosynthesis in apple fruit. PMID:26220084
Powers, Natalie R; Eicher, John D; Miller, Laura L; Kong, Yong; Smith, Shelley D; Pennington, Bruce F; Willcutt, Erik G; Olson, Richard K; Ring, Susan M; Gruen, Jeffrey R
2016-01-01
Background Reading disability (RD) and language impairment (LI) are heritable learning disabilities that obstruct acquisition and use of written and spoken language, respectively. We previously reported that two risk haplotypes, each in strong linkage disequilibrium (LD) with an allele of READ1, a polymorphic compound short tandem repeat within intron 2 of risk gene DCDC2, are associated with RD and LI. Additionally, we showed a non-additive genetic interaction between READ1 and KIAHap, a previously reported risk haplotype in risk gene KIAA0319, and that READ1 binds the transcriptional regulator ETV6. Objective To examine the hypothesis that READ1 is a transcriptional regulator of KIAA0319. Methods We characterised associations between READ1 alleles and RD and LI in a large European cohort, and also assessed interactions between READ1 and KIAHap and their effect on performance on measures of reading, language and IQ. We also used family-based data to characterise the genetic interaction, and chromatin conformation capture (3C) to investigate the possibility of a physical interaction between READ1 and KIAHap. Results and conclusions READ1 and KIAHap show interdependence—READ1 risk alleles synergise with KIAHap, whereas READ1 protective alleles act epistatically to negate the effects of KIAHap. The family data suggest that these variants interact in trans genetically, while the 3C results show that a region of DCDC2 containing READ1 interacts physically with the region upstream of KIAA0319. These data support a model in which READ1 regulates KIAA0319 expression through KIAHap and in which the additive effects of READ1 and KIAHap alleles are responsible for the trans genetic interaction. PMID:26660103