Legal regulation of protection of animals against cruelty

OpenAIRE

Spurná, Jana

2006-01-01

Diploma thesis: Legal regulation of protection of animals against cruelty This diploma thesis deals with national and transnational legal regulation of the protection of animals against cruelty. It comprises of four chapters. First chapter concerns ethical grounds of given issue and it provides analysis of term "animal welfare". Second chapter contains the most significant transnational legal rules of the protection of animals against cruelty adopted within the Council of Europe or the Europe...

Radiation protection technology. Specific course for authorized radiation protection representatives according the qualification guidelines technology for the radiation protection regulations (StrlSchV) and X-ray regulation (RoeV). 2. rev. ed.

International Nuclear Information System (INIS)

Rahn, Hans-Joachim

2012-01-01

The specific course for authorized radiation protection representatives according the qualification guidelines technology for the radiation protection regulations (StrlSchV) and X-ray regulation (RoeV). Covers the following issues: radiation protection - generally; licenses and notifications; scientific fundamentals; dosimetry, surveillance, control, documentation; technical radiation protection; radiation protection calculations.

The USA prepares to change its radiation protection regulations

International Nuclear Information System (INIS)

Anon.

1990-01-01

The US Nuclear Regulatory Commission (NRC) is preparing to revise its basic regulation on protection of people from ionizing radiation. The current regulation, ''Standards for protection against radiation'' -commonly referred to as ''Part 20'' - was originally published for comment in 1955. The regulation was based on early recommendations from the International Commission on Radiological Protection (ICRP). In 1977, the ICRP made major changes in its recommendations, known as ICRP-26. In 1990, the NRC Commissioners approved a new Part 20 reflecting ICRP-26, but improvements are to be specified and considered before a new regulation is published. (author)

A Consumer Protection Model for Regulating Lawyers.

Science.gov (United States)

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)

Radiological protection, from regulation to culture

International Nuclear Information System (INIS)

Boehler, M.C.

1996-01-01

In order to encourage a high degree of radiation protection of workers and members of public, the relevant authorities and operators in the nuclear industry should urge those responsible for radiation protection to do more than is required bu the pure and simple application of the regulations related to dose limitation compliance with the technical standards and specifications a necessary but not sufficient condition for quality in radiation protection. Reaching this quality objective is not a matter of forcing improvements bu a regulatory policy of reducing dose limits, but of promoting a real radiation protection culture based on an approach of optimizing the radiation protection formalized at the lightest level of the company structure, as well as on the professionalism individual responsibility, motivation and the freely consented to and understood participation of those involved in implementing this policy. The spread of a radiation protection culture encourages the deliberate adoption in everyday practice of behaviour likely to reduce exposure to ionizing radiation, as law as reasonably achievable, and to give life to the 'spirit' of the regulations in the best conditions. This article intends to show that the need to diffuse a radiation protection culture, particularly based on the principle of optimization, is inspired both by the philosophy behind the system recommended by the behavioural and incentive approach implied by the optimization principle. Special attention will be given to the fundamentals likely to contribute in a definition of radiation protection culture. (author)

DMPD: Negative regulation of cytoplasmic RNA-mediated antiviral signaling. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18703349 Negative regulation of cytoplasmic RNA-mediated antiviral signaling. Komur...Show Negative regulation of cytoplasmic RNA-mediated antiviral signaling. PubmedID 18703349 Title Negative r...egulation of cytoplasmic RNA-mediated antiviral signaling. Authors Komuro A, Bamm

Basis for applying for exemption according to species protection regulation. Final repository for spent nuclear fuel at Forsmark

International Nuclear Information System (INIS)

2011-02-01

SKB will submit applications for permits and admissibility under the Environmental Act and under the Nuclear Activities Act to construct and operate a disposal facility for spent nuclear fuel at Forsmark. In the final repository the spent nuclear fuel from Swedish nuclear power plants is placed in order to protect human health and the environment against harmful effects of ionizing radiation. Construction and operation of the disposal facility in Forsmark will make an impact, give effects and consequences for the natural environment. Utilization of land for the construction of the facility and the impact on ground water as a result of groundwater drainage is expected to have negative consequences for the species included in species protection regulation. Thus, the planned activity require exemption from species protection regulation (SFS 2007:845). The purpose of this document is to provide a basis for an application for exemption under 14 paragraph species protection regulation from the prohibitions of 4, 6, 7 and 8 paragraph species protection regulation. A basis for the exemption application is that the proposed activity is considered to have an 'overriding public interest' prescribed in 14 paragraph species protection regulation. The document reports the impact, effects and consequences of the planned activities on species covered in the species protection regulation. The impact on protected species can be divided into two categories: - Direct effects on protected species and their habitats by utilization of the land. - Indirect effects on protected species and their habitats in the drainage of groundwater and the effect on groundwater levels. The document also includes a description of planned actions to prevent, restrict and compensate for the effects and consequences that the activity may cause. By applying for an exemption under 14 paragraph species protection regulation in a separate order from the application for permit according to chapters 9 and 11

Radiation Protection Ordinance 1989. Supplement with Radiation Protection Register Ordinance, general administration regulation pursuant to Sect. 45 Radiation Protection Ordinance, general administration regulation pursuant to Sect. 62 sub-sect. radiation passport

International Nuclear Information System (INIS)

Veith, H.M.

1990-01-01

The addendum contains regulations issued supplementary to the Radiation Protection Ordinance: The Radiation Protection Register as of April 3, 1990 including the law on the setting up of a Federal Office on Radiation Protection; the general administration regulation pursuant to Sect. 45 Radiation Protection Ordinance as of February 21, 1990; the general administration regulation pursuant to Sect. 62 sub-sect. 2 Radiation Protection Ordinance as of May 3, 1990 (AVV Radiation passport). The volume contains, apart from the legal texts, the appropriate decision by the Bundesrat, the official explanation from the Bundestag Publications as well as a comprehensive introduction into the new legal matter. (orig.) [de

Negative regulators of brown adipose tissue (BAT)-mediated thermogenesis.

Science.gov (United States)

Sharma, Bal Krishan; Patil, Mallikarjun; Satyanarayana, Ande

2014-12-01

Brown adipose tissue (BAT) is specialized for energy expenditure, a process called adaptive thermogenesis. PET-CT scans recently demonstrated the existence of metabolically active BAT in adult humans, which revitalized our interest in BAT. Increasing the amount and/or activity of BAT holds tremendous promise for the treatment of obesity and its associated diseases. PGC1α is the master regulator of UCP1-mediated thermogenesis in BAT. A number of proteins have been identified to influence thermogenesis either positively or negatively through regulating the expression or transcriptional activity of PGC1α. Therefore, BAT activation can be achieved by either inducing the expression of positive regulators of PGC1α or by inhibiting the repressors of the PGC1α/UCP1 pathway. Here, we review the most important negative regulators of PGC1α/UCP1 signaling and their mechanism of action in BAT-mediated thermogenesis. © 2014 Wiley Periodicals, Inc.

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

Directory of Open Access Journals (Sweden)

Araceli E Santiago

2014-05-01

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

The power of extraverts: testing positive and negative mood regulation

Directory of Open Access Journals (Sweden)

Gonzalo Hervas

Full Text Available Extraversion is a personality trait which has been systematically related to positive affect and well-being. One of the mechanisms that may account for these positive outcomes is the ability to regulate the responses to positive, as well as negative, moods. Prior research has found that extraverts' higher positive mood maintenance could explain their higher levels of positive affect. However, research exploring differences between extraverts and introverts in negative mood regulation has yielded mixed results. The aim of the current study was explore the role of different facets of mood regulation displayed by extraverts, ambiverts, and introverts. After been exposed to a sad vs. happy mood induction, participants underwent a mood regulation task. Extraverts and ambiverts exhibited higher positive mood regulation than introverts, but similar mood repair. Thus, this research highlights the importance of positive mood regulation in the psychological functioning of extraverts, and opens new conceptualizations for developing interventions for introverts to improve their positive mood regulation and, hence, overall positive affect and well-being.

The development of radiation protection regulations in Malaysia

International Nuclear Information System (INIS)

Yusoff Ismail

1995-01-01

The paper begins by mentioning the established policy of the Government of Malaysia vis-a-vis protection against ionizing radiations as embodied in the Radioactive Substances Act 1968 and, later, the atomic Energy Licensing Act 1984. Then it turns to on the major events that influences the past, the present and the future development of the radiation protection regulations in Malaysia. it concludes with a vision where future Malaysia is seen drifting towards a consensus effort in radiation protection rendering self regulation the order of the day. (author)

Malfunction and failure in regulation and protection systems of PHWRs -identification of deficient areas and suggested scope of improvements

International Nuclear Information System (INIS)

Jain, A.K.; Prabhat Kumar; Arya, R.C.

1997-01-01

The reactor regulation and protection systems have changed significantly in Narora Atomic Power Station type of reactors as compared to RAPS design. As compared to total negative reactivity worth offered by moderator dump for reactor shutdown in Rajasthan Atomic Power Station, the worth of the two fast acting shutdown systems (PSS and SSS) is far lesser. In fact the worth is not even adequate to maintain the shutdown indefinitely. This has necessitated incorporation of two slow acting systems for reactor regulation and protection i.e. ALPS and GRAB systems. The negative reactivity insertion rate from fast acting PSS and SSS is however much faster as compared to moderator dump. The above changes have brought about significant changes in reactivity devices and also associated problems due to larger number of systems and equipment. The layout has also become very congested on the top of calandria vault making maintenance and inspection more cumbersome. The paper highlights the malfunction and deficiencies observed in PSS, SSS and regulating rods and identifies the further scope of improvement. (author)

Difficulties in emotion regulation mediate negative and positive affects and craving in alcoholic patients.

Science.gov (United States)

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.

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

Science.gov (United States)

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…

Regulation on radiation protection health care of workers exposed to ionizing radiation. - Regulation on radiation protection health care - of the 25 Mar 1986

International Nuclear Information System (INIS)

1986-01-01

The present regulation will be in force on 1 July 1986 and supersedes a regulation from 29 September 1970. It regulates the medical surveillance with regard to radiation protection for all kinds of workers with an increased risk of being exposed to ionizing radiation such as e.g. reactor operators and miners. Examinations have to be performed according to directions of the SAAS including further measures if necessary regarding clinical occupational and radiation protection medicine. The task of the firms, the managers, the medical officers, and the SAAS are distinctly marked

DMPD: The negative regulation of Toll-like receptor and associated pathways. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17621314 The negative regulation of Toll-like receptor and associated pathways. Lan...) Show The negative regulation of Toll-like receptor and associated pathways. PubmedID 17621314 Title The ne...gative regulation of Toll-like receptor and associated pathways. Authors Lang T,

Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells.

Science.gov (United States)

Fonseca, Sonya G; Ishigaki, Shinsuke; Oslowski, Christine M; Lu, Simin; Lipson, Kathryn L; Ghosh, Rajarshi; Hayashi, Emiko; Ishihara, Hisamitsu; Oka, Yoshitomo; Permutt, M Alan; Urano, Fumihiko

2010-03-01

Wolfram syndrome is an autosomal-recessive disorder characterized by insulin-dependent diabetes mellitus, caused by nonautoimmune loss of beta cells, and neurological dysfunctions. We have previously shown that mutations in the Wolfram syndrome 1 (WFS1) gene cause Wolfram syndrome and that WFS1 has a protective function against ER stress. However, it remained to be determined how WFS1 mitigates ER stress. Here we have shown in rodent and human cell lines that WFS1 negatively regulates a key transcription factor involved in ER stress signaling, activating transcription factor 6alpha (ATF6alpha), through the ubiquitin-proteasome pathway. WFS1 suppressed expression of ATF6alpha target genes and repressed ATF6alpha-mediated activation of the ER stress response element (ERSE) promoter. Moreover, WFS1 stabilized the E3 ubiquitin ligase HRD1, brought ATF6alpha to the proteasome, and enhanced its ubiquitination and proteasome-mediated degradation, leading to suppression of ER stress signaling. Consistent with these data, beta cells from WFS1-deficient mice and lymphocytes from patients with Wolfram syndrome exhibited dysregulated ER stress signaling through upregulation of ATF6alpha and downregulation of HRD1. These results reveal a role for WFS1 in the negative regulation of ER stress signaling and in the pathogenesis of diseases involving chronic, unresolvable ER stress, such as pancreatic beta cell death in diabetes.

Protective behavioral strategies as a mediator and moderator of the relationship between self-regulation and alcohol-related consequences in first-year college students.

Science.gov (United States)

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.

Protective microglia and its regulation in Parkinson's disease

Directory of Open Access Journals (Sweden)

Weidong Le

2016-09-01

Full Text Available Microglia mediated neuroinflammation is a hallmark of Parkinson’s disease (PD. It has been reported that microglia in the brain of PD have both neurotoxic and neuroprotective effects, depending on the microglial activation states. In this review, we will focus on the recent research findings of the neuroprotective role of microglia-mediated neuroinflammation in PD. Accumulating new evidences have indicated that the protective mechanisms of microglia may result from its regulation of transrepression pathways via nuclear receptors, anti-inflammatory responses, neuron-microglia crosstalk, histone modification and microRNA regulation. All of these protective mechanisms of microglia orchestrate with each other to repress the production of neurotoxic inflammatory components. Since the detrimental effects of inflammation overwhelm the protective effects of microglia during the disease progression of PD, exploring an in-depth understanding of the protective mechanisms of microglia and promoting the transformation of beneficial microglia are urgently important for the treatment of PD.

Regulation of positive and negative emotion: Effects of sociocultural context

Directory of Open Access Journals (Sweden)

Sara A. Snyder

2013-07-01

Full Text Available Previous research has demonstrated that the use of emotion regulation strategies can vary by sociocultural context. In a previous study, we reported changes in the use of two different emotion regulation strategies at an annual alternative cultural event, Burning Man (McRae, Heller, John, & Gross, 2011. In this sociocultural context, as compared to home, participants reported less use of expressive suppression (a strategy generally associated with maladaptive outcomes, and greater use of cognitive reappraisal (a strategy associated with adaptive outcomes. What remained unclear was whether these changes in self-reported emotion regulation strategy use were characterized by changes in the regulation of positive emotion, negative emotion, or both. We addressed this issue in the current study by asking Burning Man participants separate questions about positive and negative emotion. Using multiple datasets, we not only replicated our previous findings, but also found that the decreased use of suppression is primarily driven by reports of decreased suppression of positive emotion at Burning Man. By contrast, the reported increased use of reappraisal is not characterized by differential reappraisal of positive and negative emotion at Burning Man. Moreover, we observed novel individual differences in the magnitude of these effects. The contextual changes in self-reported suppression that we report are strongest for men and younger participants. For those who had previously attended Burning Man, we observed lower levels of self-reported suppression in both sociocultural contexts: Burning Man and home. These findings have implications for understanding the ways in which certain sociocultural contexts may decrease suppression, and possibly minimize its associated maladaptive effects.

N-wasp is essential for the negative regulation of B cell receptor signaling.

Directory of Open Access Journals (Sweden)

Chaohong Liu

2013-11-01

Full Text Available Negative regulation of receptor signaling is essential for controlling cell activation and differentiation. In B-lymphocytes, the down-regulation of B-cell antigen receptor (BCR signaling is critical for suppressing the activation of self-reactive B cells; however, the mechanism underlying the negative regulation of signaling remains elusive. Using genetically manipulated mouse models and total internal reflection fluorescence microscopy, we demonstrate that neuronal Wiskott-Aldrich syndrome protein (N-WASP, which is coexpressed with WASP in all immune cells, is a critical negative regulator of B-cell signaling. B-cell-specific N-WASP gene deletion causes enhanced and prolonged BCR signaling and elevated levels of autoantibodies in the mouse serum. The increased signaling in N-WASP knockout B cells is concurrent with increased accumulation of F-actin at the B-cell surface, enhanced B-cell spreading on the antigen-presenting membrane, delayed B-cell contraction, inhibition in the merger of signaling active BCR microclusters into signaling inactive central clusters, and a blockage of BCR internalization. Upon BCR activation, WASP is activated first, followed by N-WASP in mouse and human primary B cells. The activation of N-WASP is suppressed by Bruton's tyrosine kinase-induced WASP activation, and is restored by the activation of SH2 domain-containing inositol 5-phosphatase that inhibits WASP activation. Our results reveal a new mechanism for the negative regulation of BCR signaling and broadly suggest an actin-mediated mechanism for signaling down-regulation.

dRYBP contributes to the negative regulation of the Drosophila Imd pathway.

Directory of Open Access Journals (Sweden)

Ricardo Aparicio

Full Text Available The Drosophila humoral innate immune response fights infection by producing antimicrobial peptides (AMPs through the microbe-specific activation of the Toll or the Imd signaling pathway. Upon systemic infection, the production of AMPs is both positively and negatively regulated to reach a balanced immune response required for survival. Here, we report the function of the dRYBP (drosophila Ring and YY1 Binding Protein protein, which contains a ubiquitin-binding domain, in the Imd pathway. We have found that dRYBP contributes to the negative regulation of AMP production: upon systemic infection with Gram-negative bacteria, Diptericin expression is up-regulated in the absence of dRYBP and down-regulated in the presence of high levels of dRYBP. Epistatic analyses using gain and loss of function alleles of imd, Relish, or skpA and dRYBP suggest that dRYBP functions upstream or together with SKPA, a member of the SCF-E3-ubiquitin ligase complex, to repress the Imd signaling cascade. We propose that the role of dRYBP in the regulation of the Imd signaling pathway is to function as a ubiquitin adaptor protein together with SKPA to promote SCF-dependent proteasomal degradation of Relish. Beyond the identification of dRYBP as a novel component of Imd pathway regulation, our results also suggest that the evolutionarily conserved RYBP protein may be involved in the human innate immune response.

Will it be a better world? The proposed EU Data Protection Regulation

DEFF Research Database (Denmark)

Blume, Peter Erik

2012-01-01

•This article concerns the proposal by the European Commission to govern data protection on the basis of a regulation. It considers arguments in favour and against using a regulation with respect to general data protection law. •A regulation sustains harmonization primarily in respect to transati...... that key issues with respect to social networks have not been addressed....

Radiation protection. Scientific fundamentals, legal regulations, practical applications. Compendium

International Nuclear Information System (INIS)

Buchert, Guido; Gay, Juergen; Kirchner, Gerald; Michel, Rolf; Niggemann, Guenter; Schumann, Joerg; Wust, Peter; Jaehnert, Susanne; Strilek, Ralf; Martini, Ekkehard

2011-06-01

The compendium on radiation protection, scientific fundamentals, legal regulations and practical applications includes contributions to the following issues: (1) Effects and risk of ionizing radiation: fundamentals on effects and risk of ionizing radiation, news in radiation biology, advantages and disadvantages of screening investigations; (2) trends and legal regulations concerning radiation protection: development of European and national radiation protection laws, new regulations concerning X-rays, culture and ethics of radiation protection; (3) dosimetry and radiation measuring techniques: personal scanning using GHz radiation, new ''dose characteristics'' in practice, measuring techniques for the nuclear danger prevention and emergency hazard control; (4) radiation exposure in medicine: radiation exposure of modern medical techniques, heavy ion radiotherapy, deterministic and stochastic risks of the high-conformal photon radiotherapy, STEMO project - mobile CT for apoplectic stroke patients; (5) radiation exposure in technology: legal control of high-level radioactive sources, technical and public safety using enclosed radioactive sources for materials testing, radiation exposure in aviation, radon in Bavaria, NPP Fukushima-Daiichi - a status report; (6) radiation exposure in nuclear engineering: The Chernobyl accident - historical experiences or sustaining problem? European standards for radioactive waste disposal, radioactive material disposal in Germany risk assessment of ionizing and non-ionizing radiation (7) Case studies.

Social anxiety and alcohol-related negative consequences among college drinkers: do protective behavioral strategies mediate the association?

Science.gov (United States)

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.

RAGE, receptor of advanced glycation endoproducts, negatively regulates chondrocytes differentiation.

Directory of Open Access Journals (Sweden)

Tatsuya Kosaka

Full Text Available RAGE, receptor for advanced glycation endoproducts (AGE, has been characterized as an activator of osteoclastgenesis. However, whether RAGE directly regulates chondrocyte proliferation and differentiation is unclear. Here, we show that RAGE has an inhibitory role in chondrocyte differentiation. RAGE expression was observed in chondrocytes from the prehypertrophic to hypertrophic regions. In cultured cells, overexpression of RAGE or dominant-negative-RAGE (DN-RAGE demonstrated that RAGE inhibited cartilaginous matrix production, while DN-RAGE promoted production. Additionally, RAGE regulated Ihh and Col10a1 negatively but upregulated PTHrP receptor. Ihh promoter analysis and real-time PCR analysis suggested that downregulation of Cdxs was the key for RAGE-induced inhibition of chondrocyte differentiation. Overexpression of the NF-κB inhibitor I-κB-SR inhibited RAGE-induced NF-κB activation, but did not influence inhibition of cartilaginous matrix production by RAGE. The inhibitory action of RAGE was restored by the Rho family GTPases inhibitor Toxin B. Furthermore, inhibitory action on Ihh, Col10a1 and Cdxs was reproduced by constitutively active forms, L63RhoA, L61Rac, and L61Cdc42, but not by I-κB-SR. Cdx1 induced Ihh and Col10a1 expressions and directly interacted with Ihh promoter. Retinoic acid (RA partially rescued the inhibitory action of RAGE. These data combined suggests that RAGE negatively regulates chondrocyte differentiation at the prehypertrophic stage by modulating NF-κB-independent and Rho family GTPases-dependent mechanisms.

PGC-1-related coactivator (PRC) negatively regulates endothelial adhesion of monocytes via inhibition of NF κB activity

Energy Technology Data Exchange (ETDEWEB)

Chengye, Zhan; Daixing, Zhou, E-mail: dxzhou7246@hotmail.com; Qiang, Zhong; Shusheng, Li

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 the 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.

Financial Incentives Differentially Regulate Neural Processing of Positive and Negative Emotions during Value-Based Decision-Making

Directory of Open Access Journals (Sweden)

Anne M. Farrell

2018-02-01

Full Text Available 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.

Financial Incentives Differentially Regulate Neural Processing of Positive and Negative Emotions during Value-Based Decision-Making.

Science.gov (United States)

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.

Review of orders and regulations requiring environmental protection

International Nuclear Information System (INIS)

Kelly, E.; Cunningham, R.; Michael, D.

1996-01-01

With the increased awareness of and interest in potential ecological risks associated with past, current, and future Department of Energy (DOE) activities, DOE's Defense Programs (DP) Office of Technical and Environmental Support sponsored a study to (1) evaluate the effectiveness of the current compliance-driven environmental protection and assessment efforts relative to ecological concerns; (2) explore the need for a more focused, integrated approach to address ecological impacts; and (3) identify the requirements for an integrated approach. The study explored four questions. (a) Which federal regulations and DOE orders either explicitly require ecological assessments or implicitly require them through environmental protection language? (b) What currently is being done at selected DOE facilities to implement these regulations and orders? (c) What are private sector industries doing in terms of ecological risk assessments and how do industry approaches and issues compare with those of DOE? (d) What, if anything, in addition to current efforts is needed to ensure the protection of ecological resources associated with DOE facilities, to support defensible decision making, and to improve efficiency? The results of this study are presented in a report titled open-quotes Integrated, Comprehensive Ecological Impact Assessments In Support of Department of Energy Decision Makingclose quotes. This report is a companion document to that report. This report provides a more detailed discussion of the document reviews of the relevant environmental protection regulations and current and pending DOE orders. The main goal of the document reviews was to understand existing requirements for ecological data collection and impact assessments

Metacognitive emotion regulation: children's awareness that changing thoughts and goals can alleviate negative emotions.

Science.gov (United States)

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

Negative regulation of quorum-sensing systems in Pseudomonas aeruginosa by ATP-dependent Lon protease.

Science.gov (United States)

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.

Processing and regulation of negative emotions in anorexia nervosa: An fMRI study

Directory of Open Access Journals (Sweden)

Maria Seidel

Full Text Available Theoretical models and recent advances in the treatment of anorexia nervosa (AN have increasingly focused on the role of alterations in the processing and regulation of emotions. To date, however, our understanding of these changes is still limited and reports of emotional dysregulation in AN have been based largely on self-report data, and there is a relative lack of objective experimental evidence or neurobiological data.The current functional magnetic resonance imaging (fMRI study investigated the hemodynamic correlates of passive viewing and voluntary downregulation of negative emotions by means of the reappraisal strategy detachment in AN patients. Detachment is regarded as adaptive regulation strategy associated with a reduction in emotion-related amygdala activity and increased recruitment of prefrontal brain regions associated with cognitive control processes. Emotion regulation efficacy was assessed via behavioral arousal ratings and fMRI activation elicited by an established experimental paradigm including negative images. Participants were instructed to either simply view emotional pictures or detach themselves from feelings triggered by the stimuli.The sample consisted of 36 predominantly adolescent female AN patients and a pairwise age-matched healthy control group. Behavioral and neuroimaging data analyses indicated a reduction of arousal and amygdala activity during the regulation condition for both patients and controls. However, compared with controls, individuals with AN showed increased activation in the amygdala as well as in the right dorsolateral prefrontal cortex (dlPFC during the passive viewing of aversive compared with neutral pictures.These results extend previous findings indicative of altered processing of salient emotional stimuli in AN, but do not point to a general deficit in the voluntary regulation of negative emotions. Increased dlPFC activation in AN during passive viewing of negative stimuli is in line with

Negative regulation of neuronal cell differentiation by INHAT subunit SET/TAF-Iβ.

Science.gov (United States)

Kim, Dong-Wook; Kim, Kee-Beom; Kim, Ji-Young; Lee, Kyu-Sun; Seo, Sang-Beom

2010-09-24

Epigenetic modification plays an important role in transcriptional regulation. As a subunit of the INHAT (inhibitor of histone acetyltransferases) complex, SET/TAF-Iβ evidences transcriptional repression activity. In this study, we demonstrate that SET/TAF-Iβ is abundantly expressed in neuronal tissues of Drosophila embryos. It is expressed at high levels prior to and in early stages of neuronal development, and gradually reduced as differentiation proceeds. SET/TAF-Iβ binds to the promoters of a subset of neuronal development markers and negatively regulates the transcription of these genes. The results of this study show that the knockdown of SET/TAF-Iβ by si-RNA induces neuronal cell differentiation, thus implicating SET/TAF-Iβ as a negative regulator of neuronal development. Copyright © 2010 Elsevier Inc. All rights reserved.

Positive Gene Regulation by a Natural Protective miRNA Enables Arbuscular Mycorrhizal Symbiosis.

Science.gov (United States)

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.

Parental reactions to children's negative emotions: relationships with emotion regulation in children with an anxiety disorder.

Science.gov (United States)

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.

The general principles of radiation protection and regulation

International Nuclear Information System (INIS)

Aurengo, A.; Cesarini, J.P.; Lecomte, J.F.; Barbier, G.; Crescini, D.; Biau, A.; Blain, A.; Bailloeuil, C.; Gonin, M.; Bergot, D.

2003-01-01

Seven articles constitute this chapter about the radiation protection and the regulation. Radiological risk, reduction of public exposure to ultraviolet radiations, regulation for the radon, evolution of the French legislation against the dangers of ionizing radiations, the medical follow up after the professional life, the information system to reproduce the dosimetric data of workers, proposition of a scale to classify the radiations incidents in function of their seriousness. (N.C.)

Implementation of General Data Protection Regulation (GDPR) in Enterprises

DEFF Research Database (Denmark)

Khajuria, Samant; Sørensen, Lene Tolstrup; Skouby, Knud Erik

2017-01-01

It is impossible to keep the data secure and private when one can’t keep track of what they have, where it is and what its value is. After twenty years, Data protection Directive 95/46/EC (DPD) is finally phased out and replaced by General Data Protection Regulation (GDPR). This is a step towards...

Radiation protection and the laws and regulations

International Nuclear Information System (INIS)

Takada, Takuo

1980-01-01

In hospitals and clinics, when cobalt remote irradiation apparatuses, betatrons and linear accelerators are installed, the provisions of medical and radiation injury prevention laws and other related laws and regulations must be observed. The following matters are described: the laws and regulations concerning the prevention of radiation injuries, the definitions of the therapeutical equipments, the radiation protection standards for such facilities, radiation exposure dose and permissible dose, the procedures concerning the application before usage, the responsibilities of hospitals and clinics for radiation measurement and management, and shielding and shield calculations. (J.P.N.)

Royal Order of 22 April 1974 on Establishment of Fees in Implementation of Regulations on Protection at Work, Protection against Hazardous Equipment and Ionizing Radiations and amending the General Regulations on Protection at Work

International Nuclear Information System (INIS)

1974-01-01

This Order was made in implementation of the Act of 3 December 1969 empowering the King to establish fees in application of regulations on protection at work, dangerous equipment and ionizing radiations. In particular, it sets fees for the licensing procedure for establishment classified according to the General Regulations for the Protection of the Population and Workers against the Hazards of Ionizing Radiations of 28 February 1963. (NEA) [fr

Facial expression primes and implicit regulation of negative emotion.

Science.gov (United States)

Yoon, HeungSik; Kim, Shin Ah; Kim, Sang Hee

2015-06-17

An individual's responses to emotional information are influenced not only by the emotional quality of the information, but also by the context in which the information is presented. We hypothesized that facial expressions of happiness and anger would serve as primes to modulate subjective and neural responses to subsequently presented negative information. To test this hypothesis, we conducted a functional MRI study in which the brains of healthy adults were scanned while they performed an emotion-rating task. During the task, participants viewed a series of negative and neutral photos, one at a time; each photo was presented after a picture showing a face expressing a happy, angry, or neutral emotion. Brain imaging results showed that compared with neutral primes, happy facial primes increased activation during negative emotion in the dorsal anterior cingulated cortex and the right ventrolateral prefrontal cortex, which are typically implicated in conflict detection and implicit emotion control, respectively. Conversely, relative to neutral primes, angry primes activated the right middle temporal gyrus and the left supramarginal gyrus during the experience of negative emotion. Activity in the amygdala in response to negative emotion was marginally reduced after exposure to happy primes compared with angry primes. Relative to neutral primes, angry facial primes increased the subjectively experienced intensity of negative emotion. The current study results suggest that prior exposure to facial expressions of emotions modulates the subsequent experience of negative emotion by implicitly activating the emotion-regulation system.

Attachment's Links With Adolescents' Social Emotions: The Roles of Negative Emotionality and Emotion Regulation.

Science.gov (United States)

Murphy, Tia Panfile; Laible, Deborah J; Augustine, Mairin; Robeson, Lindsay

2015-01-01

Recent research has attempted to explain the mechanisms through which parental attachment affects social and emotional outcomes (e.g., Burnette, Taylor, Worthington, & Forsyth, 2007 ; Panfile & Laible, 2012 ). The authors' goal was to examine negative emotionality and emotion regulation as mediators of the associations that attachment has with empathy, forgiveness, guilt, and jealousy. One hundred forty-eight adolescents reported their parental attachment security, general levels of negative emotionality and abilities to regulate emotional responses, and tendencies to feel empathy, forgiveness, guilt, and jealousy. Results revealed that attachment security was associated with higher levels of empathy, forgiveness, and guilt, but lower levels of jealousy. In addition, emotion regulation mediated the links attachment shared with both empathy and guilt, such that higher levels of attachment security were linked with greater levels of emotion regulation, which led to greater levels of empathy and guilt. Alternatively, negative emotionality mediated the links attachment shared with both forgiveness and jealousy, such that higher levels of attachment security were associated with lower levels of negative emotionality, which in turn was linked to lower levels of forgiveness and higher levels of jealousy. This study provides a general picture of how attachment security may play a role in shaping an individual's levels of social emotions.

Negative regulation of EGFR/MAPK pathway by Pumilio in Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Sung Yun Kim

Full Text Available In Drosophila melanogaster, specification of wing vein cells and sensory organ precursor (SOP cells, which later give rise to a bristle, requires EGFR signaling. Here, we show that Pumilio (Pum, an RNA-binding translational repressor, negatively regulates EGFR signaling in wing vein and bristle development. We observed that loss of Pum function yielded extra wing veins and additional bristles. Conversely, overexpression of Pum eliminated wing veins and bristles. Heterozygotes for Pum produced no phenotype on their own, but greatly enhanced phenotypes caused by the enhancement of EGFR signaling. Conversely, over-expression of Pum suppressed the effects of ectopic EGFR signaling. Components of the EGFR signaling pathway are encoded by mRNAs that have Nanos Response Element (NRE-like sequences in their 3'UTRs; NREs are known to bind Pum to confer regulation in other mRNAs. We show that these NRE-like sequences bind Pum and confer repression on a luciferase reporter in heterologous cells. Taken together, our evidence suggests that Pum functions as a negative regulator of EGFR signaling by directly targeting components of the pathway in Drosophila.

A Lexical Framework for Semantic Annotation of Positive and Negative Regulation Relations in Biomedical Pathways

DEFF Research Database (Denmark)

Zambach, Sine; Lassen, Tine

presented here, we analyze 6 frequently used verbs denoting the regulation relations regulates, positively regulates and negatively regulates through corpus analysis, and propose a formal representation of the acquired knowledge as domain speci¯c semantic frames. The acquired knowledge patterns can thus...

Automatic control of negative emotions: evidence that structured practice increases the efficiency of emotion regulation.

Science.gov (United States)

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.

The Organization of Regulated Production

DEFF Research Database (Denmark)

Jansen, Jos; Jeon, Doh-Shin; Menicucci, Domenico

2008-01-01

We analyze the choice between vertical separation (VS) and vertical integration (VI) when two regulated firms produce complementary inputs with correlated costs and are protected by ex post break-even constraints. First, in the absence of collusion the regulator prefers VI (VS) for negative...

Enhanced Mucosal Defense and Reduced Tumor Burden in Mice with the Compromised Negative Regulator IRAK-M

Directory of Open Access Journals (Sweden)

Daniel E. Rothschild

2017-02-01

Full Text Available Aberrant inflammation is a hallmark of inflammatory bowel disease (IBD and colorectal cancer. IRAK-M is a critical negative regulator of TLR signaling and overzealous inflammation. Here we utilize data from human studies and Irak-m−/− mice to elucidate the role of IRAK-M in the modulation of gastrointestinal immune system homeostasis. In human patients, IRAK-M expression is up-regulated during IBD and colorectal cancer. Further functional studies in mice revealed that Irak-m−/− animals are protected against colitis and colitis associated tumorigenesis. Mechanistically, our data revealed that the gastrointestinal immune system of Irak-m−/− mice is highly efficient at eliminating microbial translocation following epithelial barrier damage. This attenuation of pathogenesis is associated with expanded areas of gastrointestinal associated lymphoid tissue (GALT, increased neutrophil migration, and enhanced T-cell recruitment. Further evaluation of Irak-m−/− mice revealed a splice variant that robustly activates NF-κB signaling. Together, these data identify IRAK-M as a potential target for future therapeutic intervention.

Search 40 Code of Federal Regulations (CFR): Protection of the Environment

Data.gov (United States)

U.S. Environmental Protection Agency — Title 40 is the section of the Code of Federal Regulations (CFR) that deals with EPA's mission of protecting human health and the environment. This web page provides...

Osteocalcin as a negative regulator of serum leptin concentration in humans: insight from triathlon competitions.

Science.gov (United States)

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.

The protection of minors in the new audiovisual regulation in Spain

Directory of Open Access Journals (Sweden)

José A. Ruiz-San Román, Ph.D.

2011-01-01

Full Text Available In 2010 the Spanish Parliament approved the General Law on Audiovisual Communication (GLAC, a new regulation which implements the European Audiovisual Media Services Directive (AVMSD. This research analyses how the regulations focused on the protection of children evolved throughout the legislative process, from the first text drafted by the Government to the text finally approved by Parliament. The research deals with the debates and amendments on harmful content which is prohibited or limited. The main objective of the research is to establish the extent to what the new regulation approved in Spain meets the requirements fixed by the AVMSD and the Spanish Government to guarantee child protection.

Accidents protection of the de-Qing regulator

International Nuclear Information System (INIS)

Feng Wenquan; Yang Fangxin; Zhu Genfa; Chen Zhenhua

1992-01-01

The de-Qing circuit is widely used in regulating and stabilizing HV pulse voltage in radar and electron linac. however its malfunction may cause damage to the microwave tube and pulse generator. Thus it is necessary to set up a protection circuit. The principle and problems for design are presented. Two examples employed successfully in electron linac are provided

Strong negative self regulation of Prokaryotic transcription factors increases the intrinsic noise of protein expression

Directory of Open Access Journals (Sweden)

Jenkins Dafyd J

2008-01-01

Full Text Available Abstract Background Many prokaryotic transcription factors repress their own transcription. It is often asserted that such regulation enables a cell to homeostatically maintain protein abundance. We explore the role of negative self regulation of transcription in regulating the variability of protein abundance using a variety of stochastic modeling techniques. Results We undertake a novel analysis of a classic model for negative self regulation. We demonstrate that, with standard approximations, protein variance relative to its mean should be independent of repressor strength in a physiological range. Consequently, in that range, the coefficient of variation would increase with repressor strength. However, stochastic computer simulations demonstrate that there is a greater increase in noise associated with strong repressors than predicted by theory. The discrepancies between the mathematical analysis and computer simulations arise because with strong repressors the approximation that leads to Michaelis-Menten-like hyperbolic repression terms ceases to be valid. Because we observe that strong negative feedback increases variability and so is unlikely to be a mechanism for noise control, we suggest instead that negative feedback is evolutionarily favoured because it allows the cell to minimize mRNA usage. To test this, we used in silico evolution to demonstrate that while negative feedback can achieve only a modest improvement in protein noise reduction compared with the unregulated system, it can achieve good improvement in protein response times and very substantial improvement in reducing mRNA levels. Conclusion Strong negative self regulation of transcription may not always be a mechanism for homeostatic control of protein abundance, but instead might be evolutionarily favoured as a mechanism to limit the use of mRNA. The use of hyperbolic terms derived from quasi-steady-state approximation should also be avoided in the analysis of stochastic

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

Science.gov (United States)

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

2015-01-01

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

Mothers' responses to children's negative emotions and child emotion regulation: the moderating role of vagal suppression.

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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.

Instrumental motives in negative emotion regulation in daily life: Frequency, consistency, and predictors.

Science.gov (United States)

Kalokerinos, Elise K; Tamir, Maya; Kuppens, Peter

2017-06-01

People regulate their emotions not only for hedonic reasons but also for instrumental reasons, to attain the potential benefits of emotions beyond pleasure and pain. However, such instrumental motives have rarely been examined outside the laboratory as they naturally unfold in daily life. To assess whether and how instrumental motives operate outside the laboratory, it is necessary to examine them in response to real and personally relevant stimuli in ecologically valid contexts. In this research, we assessed the frequency, consistency, and predictors of instrumental motives in negative emotion regulation in daily life. Participants (N = 114) recalled the most negative event of their day each evening for 7 days and reported their instrumental motives and negative emotion goals in that event. Participants endorsed performance motives in approximately 1 in 3 events and social, eudaimonic, and epistemic motives in approximately 1 in 10 events. Instrumental motives had substantially higher within- than between-person variance, indicating that they were context-dependent. Indeed, although we found few associations between instrumental motives and personality traits, relationships between instrumental motives and contextual variables were more extensive. Performance, social, and epistemic motives were each predicted by a unique pattern of contextual appraisals. Our data demonstrate that instrumental motives play a role in daily negative emotion regulation as people encounter situations that pose unique regulatory demands. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Desirable changes in the legal radiation protection regulations in Austria

International Nuclear Information System (INIS)

Holeczke, F.

1988-01-01

The complexity of the Austrian Radiation Protection Law ranging from nuclear reactors up to odontoradiographs hampers its amendment so that merely an amendment of the Radiation Protection Ordinance seems to be feasible. Suggestions for amendments should orient themselves along experience made in practice. In particular amendments of the regulations on the period for safekeeping the records in radiodiagnostics, on the final examination of persons exposed to radiation in the case of termination of employment as well as of Sec. 34, 41 Subsec. 2 and Sec. 62, Subsec. 1 would be desirable. The latter concern technical regulations, the monitored area and the equipment for the soft-ray technique. (DG) [de

When less is more: Effects of the availability of strategic options on regulating negative emotions.

Science.gov (United States)

Bigman, Yochanan E; Sheppes, Gal; Tamir, Maya

2017-09-01

Research in several domains suggests that having strategic options is not always beneficial. In this paper, we tested whether having strategic options (vs. not) is helpful or harmful for regulating negative emotions. In 5 studies (N = 151) participants were presented with 1 or more strategic options prior to watching aversive images and using the selected strategic option. Across studies, we found that people reported less intense negative emotions when the strategy they used to regulate their emotions was presented as a single option, rather than as 1 of several options. This was regardless of whether people could choose between the options (Studies 3-5) or not (Studies 1, 2, and 4), and specific to negative (but not neutral) images (Study 5). A sixth study addressed an explanation based on demand characteristics, showing that participants expected to feel more positive when having more than 1 option. The findings indicate that having strategic options for regulating negative emotions can sometimes be costly. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Mutation analysis of the negative regulator cyclin G2 in gastric cancer

African Journals Online (AJOL)

Jane

2011-10-24

Oct 24, 2011 ... Key words: Cyclin G2, gastric cancer, negative regulator, mutation screen. INTRODUCTION ... cerebellum, thymus, spleen, prostate, kidney and the immune ..... and B cell antigen receptor-mediated cell cycle arrest. J. Biol.

76 FR 20569 - Horse Protection Act; Petition for Amendments to Regulations

Science.gov (United States)

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...

TLX is an intrinsic regulator of the negative effects of IL-1β on proliferating hippocampal neural progenitor cells.

Science.gov (United States)

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.

Legal and technical regulations in radiation protection and their effects on radiotherapy

International Nuclear Information System (INIS)

Betz, B.

1975-01-01

During the last few years, new regulations and guidelines in the field of radiation protection have been issued which affect radiotherapy, too. On September 1st, 1973 the X-ray Ordinance became effective; a few weeks later, new guidelines for radiation protections when using radioactive substances in the field of medicine were published. Of particular topical interest is the appendix of these new guidelines, in which the principles of technical competence in radiation protection when handling radioactive substances in the field of medicine are laid down uniformly for the FRG. Amongst these more recent regulations, there is also the direction by the Minister of the Interior to put the operation of accelerators in the field of medicine according to section 19 of the Atomic Energy Act under the supervision of the state and to employ newly issued administrative guidelines. After a short survey on the radiation protection laws in force, a selection of important stipulations within the new legal regulations and guidelines is discussed with a view to their effects on radiotherapy. (orig./LN) [de

Modeling the role of negative cooperativity in metabolic regulation and homeostasis.

Directory of Open Access Journals (Sweden)

Eliot C Bush

Full Text Available A significant proportion of enzymes display cooperativity in binding ligand molecules, and such effects have an important impact on metabolic regulation. This is easiest to understand in the case of positive cooperativity. Sharp responses to changes in metabolite concentrations can allow organisms to better respond to environmental changes and maintain metabolic homeostasis. However, despite the fact that negative cooperativity is almost as common as positive, it has been harder to imagine what advantages it provides. Here we use computational models to explore the utility of negative cooperativity in one particular context: that of an inhibitor binding to an enzyme. We identify several factors which may contribute, and show that acting together they can make negative cooperativity advantageous.

A Comparison of Autonomous Regulation and Negative Self-Evaluative Emotions as Predictors of Smoking Behavior Change among College Students

Science.gov (United States)

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

A comparison of autonomous regulation and negative self-evaluative emotions as predictors of smoking behavior change among college students.

Science.gov (United States)

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.

Expression of Androgen Receptor Is Negatively Regulated By p53

Directory of Open Access Journals (Sweden)

Fatouma Alimirah

2007-12-01

Full Text Available Increased expression of androgen receptor (AR in prostate cancer (PC is associated with transition to androgen independence. Because the progression of PC to advanced stages is often associated with the loss of p53 function, we tested whether the p53 could regulate the expression of AR gene. Here we report that p53 negatively regulates the expression of AR in prostate epithelial cells (PrECs. We found that in LNCaP human prostate cancer cells that express the wild-type p53 and AR and in human normal PrECs, the activation of p53 by genotoxic stress or by inhibition of p53 nuclear export downregulated the expression of AR. Furthermore, forced expression of p53 in LNCaP cells decreased the expression of AR. Conversely, knockdown of p53 expression in LNCaP cells increased the AR expression. Consistent with the negative regulation of AR expression by p53, the p53-null HCT116 cells expressed higher levels of AR compared with the isogenic HCT116 cells that express the wildtype p53. Moreover, we noted that in etoposide treated LNCaP cells p53 bound to the promoter region of the AR gene, which contains a potential p53 DNA-binding consensus sequence, in chromatin immunoprecipitation assays. Together, our observations provide support for the idea that the loss of p53 function in prostate cancer cells contributes to increased expression of AR.

Regulation on protection against ionizing radiations

International Nuclear Information System (INIS)

1995-01-01

This regulation has as the objective to establish the criteria tending toward protecting the health of the population of the radiologic risks that can be derive from the employment of the ionizing radiations and similar activities. It establishes the requirements to comply with the radiactive installations, equipment transmitters of ionizing radiations, personal that works in them, operate the equipment and carry out any another similar activity such as: production, importation, exportation, transportation, transference of radioactive material or equipment generators of radiations ionizing. (S. Grainger) [es

Maternal depression and anxiety, social synchrony, and infant regulation of negative and positive emotions.

Science.gov (United States)

Granat, Adi; Gadassi, Reuma; Gilboa-Schechtman, Eva; Feldman, Ruth

2017-02-01

Maternal postpartum depression (PPD) exerts long-term negative effects on infants; yet the mechanisms by which PPD disrupts emotional development are not fully clear. Utilizing an extreme-case design, 971 women reported symptoms of depression and anxiety following childbirth and 215 high and low on depressive symptomatology reported again at 6 months. Of these, mothers diagnosed with major depressive disorder (n = 22), anxiety disorders (n = 19), and controls (n = 59) were visited at 9 months. Mother-infant interaction was microcoded for maternal and infant's social behavior and synchrony. Infant negative and positive emotional expression and self-regulation were tested in 4 emotion-eliciting paradigms: anger with mother, anger with stranger, joy with mother, and joy with stranger. Infants of depressed mothers displayed less social gaze and more gaze aversion. Gaze and touch synchrony were lowest for depressed mothers, highest for anxious mothers, and midlevel among controls. Infants of control and anxious mothers expressed less negative affect with mother compared with stranger; however, maternal presence failed to buffer negative affect in the depressed group. Maternal depression chronicity predicted increased self-regulatory behavior during joy episodes, and touch synchrony moderated the effects of PPD on infant self-regulation. Findings describe subtle microlevel processes by which maternal depression across the postpartum year disrupts the development of infant emotion regulation and suggest that diminished social synchrony, low differentiation of attachment and nonattachment contexts, and increased self-regulation during positive moments may chart pathways for the cross-generational transfer of emotional maladjustment from depressed mothers to their infants. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Wheat CBL-interacting protein kinase 25 negatively regulates salt tolerance in transgenic wheat

OpenAIRE

Jin, Xia; Sun, Tao; Wang, Xiatian; Su, Peipei; Ma, Jingfei; He, Guangyuan; Yang, Guangxiao

2016-01-01

CBL-interacting protein kinases are involved in plant responses to abiotic stresses, including salt stress. However, the negative regulating mechanism of this gene family in response to salinity is less reported. In this study, we evaluated the role of TaCIPK25 in regulating salt response in wheat. Under conditions of high salinity, TaCIPK25 expression was markedly down-regulated in roots. Overexpression of TaCIPK25 resulted in hypersensitivity to Na+ and superfluous accumulation of Na+ in tr...

Age Differences in the Influence of Induced Negative Emotion on Decision-Making: The Role of Emotion Regulation.

Science.gov (United States)

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.

Flg22-Triggered Immunity Negatively Regulates Key BR Biosynthetic Genes.

Science.gov (United States)

Jiménez-Góngora, Tamara; Kim, Seong-Ki; Lozano-Durán, Rosa; Zipfel, Cyril

2015-01-01

In plants, activation of growth and activation of immunity are opposing processes that define a trade-off. In the past few years, the growth-promoting hormones brassinosteroids (BR) have emerged as negative regulators of pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), promoting growth at the expense of defense. The crosstalk between BR and PTI signaling was described as negative and unidirectional, since activation of PTI does not affect several analyzed steps in the BR signaling pathway. In this work, we describe that activation of PTI by the bacterial PAMP flg22 results in the reduced expression of BR biosynthetic genes. This effect does not require BR perception or signaling, and occurs within 15 min of flg22 treatment. Since the described PTI-induced repression of gene expression may result in a reduction in BR biosynthesis, the crosstalk between PTI and BR could actually be negative and bidirectional, a possibility that should be taken into account when considering the interaction between these two pathways.

BRAFV600E negatively regulates the AKT pathway in melanoma cell lines.

Science.gov (United States)

Chen, Brenden; Tardell, Christine; Higgins, Brian; Packman, Kathryn; Boylan, John F; Niu, Huifeng

2012-01-01

Cross-feedback activation of MAPK and AKT pathways is implicated as a resistance mechanism for cancer therapeutic agents targeting either RAF/MEK or PI3K/AKT/mTOR. It is thus important to have a better understanding of the molecular resistance mechanisms to improve patient survival benefit from these agents. Here we show that BRAFV600E is a negative regulator of the AKT pathway. Expression of BRAFV600E in NIH3T3 cells significantly suppresses MEK inhibitor (RG7167) or mTORC1 inhibitor (rapamycin) induced AKT phosphorylation (pAKT) and downstream signal activation. Treatment-induced pAKT elevation is found in BRAF wild type melanoma cells but not in a subset of melanoma cell lines harboring BRAFV600E. Knock-down of BRAFV600E in these melanoma cells elevates basal pAKT and downstream signals, whereas knock-down of CRAF, MEK1/2 or ERK1/2 or treatment with a BRAF inhibitor have no impact on pAKT. Mechanistically, we show that BRAFV600E interacts with rictor complex (mTORC2) and regulates pAKT through mTORC2. BRAFV600E is identified in mTORC2 after immunoprecipitation of rictor. Knock-down of rictor abrogates BRAFV600E depletion induced pAKT. Knock-down of BRAFV600E enhances cellular enzyme activity of mTORC2. Aberrant activation of AKT pathway by PTEN loss appears to override the negative impact of BRAFV600E on pAKT. Taken together, our findings suggest that in a subset of BRAFV600E melanoma cells, BRAFV600E negatively regulates AKT pathway in a rictor-dependent, MEK/ERK and BRAF kinase-independent manner. Our study reveals a novel molecular mechanism underlying the regulation of feedback loops between the MAPK and AKT pathways.

BRAFV600E negatively regulates the AKT pathway in melanoma cell lines.

Directory of Open Access Journals (Sweden)

Brenden Chen

Full Text Available Cross-feedback activation of MAPK and AKT pathways is implicated as a resistance mechanism for cancer therapeutic agents targeting either RAF/MEK or PI3K/AKT/mTOR. It is thus important to have a better understanding of the molecular resistance mechanisms to improve patient survival benefit from these agents. Here we show that BRAFV600E is a negative regulator of the AKT pathway. Expression of BRAFV600E in NIH3T3 cells significantly suppresses MEK inhibitor (RG7167 or mTORC1 inhibitor (rapamycin induced AKT phosphorylation (pAKT and downstream signal activation. Treatment-induced pAKT elevation is found in BRAF wild type melanoma cells but not in a subset of melanoma cell lines harboring BRAFV600E. Knock-down of BRAFV600E in these melanoma cells elevates basal pAKT and downstream signals, whereas knock-down of CRAF, MEK1/2 or ERK1/2 or treatment with a BRAF inhibitor have no impact on pAKT. Mechanistically, we show that BRAFV600E interacts with rictor complex (mTORC2 and regulates pAKT through mTORC2. BRAFV600E is identified in mTORC2 after immunoprecipitation of rictor. Knock-down of rictor abrogates BRAFV600E depletion induced pAKT. Knock-down of BRAFV600E enhances cellular enzyme activity of mTORC2. Aberrant activation of AKT pathway by PTEN loss appears to override the negative impact of BRAFV600E on pAKT. Taken together, our findings suggest that in a subset of BRAFV600E melanoma cells, BRAFV600E negatively regulates AKT pathway in a rictor-dependent, MEK/ERK and BRAF kinase-independent manner. Our study reveals a novel molecular mechanism underlying the regulation of feedback loops between the MAPK and AKT pathways.

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-07-15

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

A general description of the Swedish radiation protection regulations of radioactive sources

International Nuclear Information System (INIS)

Staalnacke, C.-G.

2001-01-01

The regulation of ionizing radiation in Sweden is based on both the Radiation Protection Act and Ordinance from 1998. The Swedish Radiation Protection Institute (SSI) acts as the regulatory authority for radiation safety and issues detailed regulations in specific areas. The report summarizes how the SSI controls radiation sources, including orphan sources for which a process for analyzing their occurrence has started in Sweden. A number of proposed procedures for the control and follow-up of sealed radioactive sources is provided. (author)

TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production.

Science.gov (United States)

McNab, Finlay W; Ewbank, John; Rajsbaum, Ricardo; Stavropoulos, Evangelos; Martirosyan, Anna; Redford, Paul S; Wu, Xuemei; Graham, Christine M; Saraiva, Margarida; Tsichlis, Philip; Chaussabel, Damien; Ley, Steven C; O'Garra, Anne

2013-08-15

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading cause of mortality and morbidity worldwide, causing ≈ 1.4 million deaths per year. Key immune components for host protection during tuberculosis include the cytokines IL-12, IL-1, and TNF-α, as well as IFN-γ and CD4(+) Th1 cells. However, immune factors determining whether individuals control infection or progress to active tuberculosis are incompletely understood. Excess amounts of type I IFN have been linked to exacerbated disease during tuberculosis in mouse models and to active disease in patients, suggesting tight regulation of this family of cytokines is critical to host resistance. In addition, the immunosuppressive cytokine IL-10 is known to inhibit the immune response to M. tuberculosis in murine models through the negative regulation of key proinflammatory cytokines and the subsequent Th1 response. We show in this study, using a combination of transcriptomic analysis, genetics, and pharmacological inhibitors, that the TPL-2-ERK1/2 signaling pathway is important in mediating host resistance to tuberculosis through negative regulation of type I IFN production. The TPL-2-ERK1/2 signaling pathway regulated production by macrophages of several cytokines important in the immune response to M. tuberculosis as well as regulating induction of a large number of additional genes, many in a type I IFN-dependent manner. In the absence of TPL-2 in vivo, excess type I IFN promoted IL-10 production and exacerbated disease. These findings describe an important regulatory mechanism for controlling tuberculosis and reveal mechanisms by which type I IFN may promote susceptibility to this important disease.

CBL-interacting protein kinase 6 negatively regulates immune response to Pseudomonas syringae in Arabidopsis.

Science.gov (United States)

Sardar, Atish; Nandi, Ashis Kumar; Chattopadhyay, Debasis

2017-06-15

Cytosolic calcium ion (Ca2+) is an essential mediator of the plant innate immune response. Here, we report that a calcium-regulated protein kinase Calcineurin B-like protein (CBL)-interacting protein kinase 6 (CIPK6) functions as a negative regulator of immunity against the bacterial pathogen Pseudomonas syringae in Arabidopsis thaliana. Arabidopsis lines with compromised expression of CIPK6 exhibited enhanced disease resistance to the bacterial pathogen and to P. syringae harboring certain but not all avirulent effectors, while restoration of CIPK6 expression resulted in abolition of resistance. Plants overexpressing CIPK6 were more susceptible to P. syringae. Enhanced resistance in the absence of CIPK6 was accompanied by increased accumulation of salicylic acid and elevated expression of defense marker genes. Salicylic acid accumulation was essential for improved immunity in the absence of CIPK6. CIPK6 negatively regulated the oxidative burst associated with perception of pathogen-associated microbial patterns (PAMPs) and bacterial effectors. Accelerated and enhanced activation of the mitogen-activated protein kinase cascade in response to bacterial and fungal elicitors was observed in the absence of CIPK6. The results of this study suggested that CIPK6 negatively regulates effector-triggered and PAMP-triggered immunity in Arabidopsis. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

New legislative regulations for ensuring radiation protection using ionizing radiation sources in medicine

International Nuclear Information System (INIS)

Boehm, K.

2018-01-01

European Commission Directive No. 2013/59 / EURATOM laying down basic safety requirements for the provision of radiation protection regulates the provision of radiation protection for workers with radiation sources and residents in all areas of use of ionizing radiation sources. This Directive also addresses radiation protection in the use of ionizing radiation sources in medicine. The European Commission Directive regulates the requirements for radiation protection but also extends to its scope and provisions on the use of medical radiation sources (so-called m edical exposure ) in the scope of further legislation in the field of health care, which has to be amended and modified or possibly issued new. It was necessary in the preparation of the new act on radiation protection to amend simultaneously Act no. 576/2004 on the provision of health care and services related to provision of health care and Act no. 578/2004 on Health care Providers, Health care Professionals and Organizations in Health Care and to prepare a series of implementing regulations not only to the Law on Radiation Protection but also to the Laws governing the Provision of Health Care. The paper presents changes to existing legislation on radiation protection in medical radiation and new requirements for the construction and operation of health workplaces with radiation sources, the protection of the health of patients, the requirements for instrumentation used for medical radiation and radiological instrumentation tests. (authors)

Radiation protection for nurses. Regulations and guidelines

International Nuclear Information System (INIS)

Jankowski, C.B.

1992-01-01

Rules and regulations of federal agencies and state radiation protection programs provide the bases for hospital policy regarding radiation safety for nurses. Nursing administrators should work with the radiation safety officer at their institutions to ensure that radiation exposures to staff nurses will be as low as reasonably achievable and that special consideration will be given to pregnant nurses. Nurses' fears about their exposure to radiation can be greatly reduced through education

PhERF6, interacting with EOBI, negatively regulates fragrance biosynthesis in petunia flowers.

Science.gov (United States)

Liu, Fei; Xiao, Zhina; Yang, Li; Chen, Qian; Shao, Lu; Liu, Juanxu; Yu, Yixun

2017-09-01

In petunia, the production of volatile benzenoids/phenylpropanoids determines floral aroma, highly regulated by development, rhythm and ethylene. Previous studies identified several R2R3-type MYB trans-factors as positive regulators of scent biosynthesis in petunia flowers. Ethylene response factors (ERFs) have been shown to take part in the signal transduction of hormones, and regulation of metabolism and development processes in various plant species. Using virus-induced gene silencing technology, a negative regulator of volatile benzenoid biosynthesis, PhERF6, was identified by a screen for regulators of the expression of genes related to scent production. PhERF6 expression was temporally and spatially connected with scent production and was upregulated by exogenous ethylene. Up-/downregulation of the mRNA level of PhERF6 affected the expression of ODO1 and several floral scent-related genes. PhERF6 silencing led to a significant increase in the concentrations of volatiles emitted by flowers. Yeast two-hybrid, bimolecular fluorescence complementation and co-immunoprecipitation assays indicated that PhERF6 interacted with the N-terminus of EOBI, which includes two DNA binding domains. Our results show that PhERF6 negatively regulates volatile production in petunia flowers by competing for the binding of the c-myb domains of the EOBI protein with the promoters of genes related to floral scent. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Prior exposure to repeated immobilization or chronic unpredictable stress protects from some negative sequels of an acute immobilization.

Science.gov (United States)

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.

77 FR 41699 - Transportation of Household Goods in Interstate Commerce; Consumer Protection Regulations...

Science.gov (United States)

2012-07-16

... regulations to require HHG brokers to comply with certain consumer protection requirements. As a part of that... that rule, if an individual shipper elects to waive physical receipt of the consumer protection... receipts documenting an individual shipper's waiver of physical receipt of the consumer protection...

Cloud accountability : The likely impact of the proposed EU Data Protection Regulation

NARCIS (Netherlands)

Hon, W.Kuan; Kosta, E.; Millard, Christopher; Stefanatou, D.

2014-01-01

This Working Paper considers the implications for cloud accountability of current proposals under the draft General Data Protection Regulation to modernise the EU Data Protection Directive. It makes recommendations aimed at improving the technology-neutrality of the proposals and their

[Regulation of Positive and Negative Emotions as Mediator between Maternal Emotion Socialization and Child Problem Behavior].

Science.gov (United States)

Fäsche, Anika; Gunzenhauser, Catherine; Friedlmeier, Wolfgang; von Suchodoletz, Antje

2015-01-01

The present study investigated five to six year old children's ability to regulate negative and positive emotions in relation to psychosocial problem behavior (N=53). It was explored, whether mothers' supportive and nonsupportive strategies of emotion socialization influence children's problem behavior by shaping their emotion regulation ability. Mothers reported on children's emotion regulation and internalizing and externalizing problem behavior via questionnaire, and were interviewed about their preferences for socialization strategies in response to children's expression of negative affect. Results showed that children with more adaptive expression of adequate positive emotions had less internalizing behavior problems. When children showed more control of inadequate negative emotions, children were less internalizing as well as externalizing in their behavior. Furthermore, results indicated indirect relations of mothers' socialization strategies with children's problem behavior. Control of inadequate negative emotions mediated the link between non-supportive strategies on externalizing problem behavior. Results suggest that emotion regulatory processes should be part of interventions to reduce the development of problematic behavior in young children. Parents should be trained in dealing with children's emotions in a constructive way.

The effect of arousal on regulation of negative emotions using cognitive reappraisal: An ERP study.

Science.gov (United States)

Langeslag, Sandra J E; Surti, Kruti

2017-08-01

Because the effectiveness of the emotion regulation strategy cognitive reappraisal may vary with emotion intensity, we investigated how stimulus arousal affects reappraisal success. Participants up- and down-regulated emotional responses using cognitive reappraisal to low and high arousing unpleasant pictures while the electroencephalogram (EEG) was recorded. Up-regulation resulted in more negative self-reported valence, while down-regulation resulted in less negative self-reported valence regardless of stimulus arousal, suggesting that subjective reappraisal success does not vary with emotional intensity. Participants felt that down-regulation of emotional responses to low arousing unpleasant pictures was easiest, which is in line with previous findings that participants showed a greater preference for reappraisal in low than high arousing situations. The late positive potential (LPP) amplitude was enhanced by down-regulation of high arousing unpleasant pictures. Even though this effect was unexpected and is opposite to the typical effect of down-regulation on the LPP, it is in line with several previous studies. Potential explanations for LPP regulation effects in the unexpected direction, such as strategy selection and task design, are evaluated. Suggestions and recommendations for future research are discussed, including using trial-by-trial manipulation of regulation instructions and studying the effect of stimulus arousal on up- and down-regulation of positive emotions. Copyright © 2017 Elsevier B.V. All rights reserved.

Emotion regulation strategies mediate the associations of positive and negative affect to upper extremity physical function.

Science.gov (United States)

Talaei-Khoei, Mojtaba; Nemati-Rezvani, Hora; Fischerauer, Stefan F; Ring, David; Chen, Neal; Vranceanu, Ana-Maria

2017-05-01

The Gross process model of emotion regulation holds that emotion-eliciting situations (e.g. musculoskeletal illness) can be strategically regulated to determine the final emotional and behavioral response. Also, there is some evidence that innate emotional traits may predispose an individual to a particular regulating coping style. We enrolled 107 patients with upper extremity musculoskeletal illness in this cross-sectional study. They completed self-report measures of positive and negative affect, emotion regulation strategies (cognitive reappraisal and expressive suppression), upper extremity physical function, pain intensity, and demographics. We used Preacher and Hayes' bootstrapping approach to process analysis to infer the direct effect of positive and negative affect on physical function as well as their indirect effects through activation of emotion regulation strategies. Negative affect was associated with decreased physical function. The association was partly mediated by expressive suppression (b (SE)=-.10 (.05), 95% BCa CI [-.21, -.02]). Positive affect was associated with increased physical function. Cognitive reappraisal partially mediated this association (b (SE)=.11 (.05), 95% BCa CI [.03, .24]). After controlling for pain intensity, the ratio of the mediated effect to total effect grew even larger in controlled model comparing to uncontrolled model (33% vs. 26% for expressive suppression and 32% vs. 30% for cognitive reappraisal). The relationships between affect, emotion regulation strategies and physical function appear to be more dependent on the emotional response to an orthopedic condition rather than the intensity of the nociceptive stimulation of the pain. Findings support integration of emotion regulation training in skill-based psychotherapy in this population to mitigate the effect of negative affect and enhance the influence of positive affect on physical function. Copyright © 2017 Elsevier Inc. All rights reserved.

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Trait Affect, Emotion Regulation, and the Generation of Negative and Positive Interpersonal Events.

Science.gov (United States)

Hamilton, Jessica L; Burke, Taylor A; Stange, Jonathan P; Kleiman, Evan M; Rubenstein, Liza M; Scopelliti, Kate A; Abramson, Lyn Y; Alloy, Lauren B

2017-07-01

Positive and negative trait affect and emotion regulatory strategies have received considerable attention in the literature as predictors of psychopathology. However, it remains unclear whether individuals' trait affect is associated with responses to state positive affect (positive rumination and dampening) or negative affect (ruminative brooding), or whether these affective experiences contribute to negative or positive interpersonal event generation. Among 304 late adolescents, path analyses indicated that individuals with higher trait negative affect utilized dampening and brooding rumination responses, whereas those with higher trait positive affect engaged in rumination on positive affect. Further, there were indirect relationships between trait negative affect and fewer positive and negative interpersonal events via dampening, and between trait positive affect and greater positive and negative interpersonal events via positive rumination. These findings suggest that individuals' trait negative and positive affect may be associated with increased utilization of emotion regulation strategies for managing these affects, which may contribute to the occurrence of positive and negative events in interpersonal relationships. Copyright © 2017. Published by Elsevier Ltd.

The future of environmental protection: A U.S. regulator's perspective

International Nuclear Information System (INIS)

Dicus, G.J.

2002-01-01

The U.S. has the largest number of nuclear installations of any country in the world. This puts us at an extreme end of the spectrum. As a result, I have touched on many issues relative to environmental protection. Therefore in summary, let me list these issues: Before moving ahead, look at what has been done thus far. Executive policy and a national regulatory infrastructure. - Environmental Impact Statements. - Environmental Justice. Standards determined by law or courts. Consultation with other national agencies and countries. Improving the timetable for issuing regulations and supporting guidance. Improved communications and training of staff. Transparency and flexibility throughout the regulatory process. Differences in regulatory approaches are OK, as long as the end result is to achieve sound national environmental and public health and safety policy. I believe that this series of conferences represents an excellent opportunity to come to resolution about the future of environmental regulations and policies. Having this information will assist us in harmonizing any proposed recommendation(s) for radiological protection of the environment involving commodities containing radioactive materials or unrestricted release of slightly radioactive materials by using the existing environmental radiation protection framework as a starting point. Doing so in an open, encompassing manner will, in my opinion, go a long way towards resolving some of the current controversies about radiation protection standards in the U.S., as well as around the world, with the desirable end result of increasing public confidence in our environmental radiation protection programs. (author)

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-06-10

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

Negative regulation of MAP kinase signaling in Drosophila by Ptp61F/PTP1B.

Science.gov (United States)

Tchankouo-Nguetcheu, Stéphane; Udinotti, Mario; Durand, Marjorie; Meng, Tzu-Ching; Taouis, Mohammed; Rabinow, Leonard

2014-10-01

PTP1B is an important negative regulator of insulin and other signaling pathways in mammals. However, the role of PTP1B in the regulation of RAS-MAPK signaling remains open to deliberation, due to conflicting evidence from different experimental systems. The Drosophila orthologue of mammalian PTP1B, PTP61F, has until recently remained largely uncharacterized. To establish the potential role of PTP61F in the regulation of signaling pathways in Drosophila and particularly to help resolve its fundamental function in RAS-MAPK signaling, we generated a new allele of Ptp61F as well as employed both RNA interference and overexpression alleles. Our results validate recent data showing that the activity of insulin and Abl kinase signaling is increased in Ptp61F mutants and RNA interference lines. Importantly, we establish negative regulation of the RAS/MAPK pathway by Ptp61F activity in whole animals. Of particular interest, our results document the modulation of hyperactive MAP kinase activity by Ptp61F alleles, showing that the phosphatase intervenes to directly or indirectly regulate MAP kinase itself.

The impact of thin idealized media images on body satisfaction: does body appreciation protect women from negative effects?

Science.gov (United States)

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.

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

Science.gov (United States)

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.…

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

Science.gov (United States)

Lüdecke, Christina; Baumann, Nicola

2015-12-01

Terror management theory assumes that death arouses existential anxiety in humans which is suppressed in focal attention. Whereas most studies provide indirect evidence for negative affect under mortality salience by showing cultural worldview defenses and self-esteem strivings, there is only little direct evidence for implicit negative affect under mortality salience. In the present study, we assume that this implicit affective reaction towards death depends on people's ability to self-regulate negative affect as assessed by the personality dimension of action versus state orientation. Consistent with our expectations, action-oriented participants judged artificial words to express less negative affect under mortality salience compared to control conditions whereas state-oriented participants showed the reversed pattern. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Does Self-Esteem Moderate the Associations between Protective Behavioral Strategies and Negative Outcomes Associated with Alcohol Consumption?

Science.gov (United States)

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.…

Quorum sensing negatively regulates chitinase in Vibrio harveyi.

Science.gov (United States)

Defoirdt, Tom; Darshanee Ruwandeepika, H A; Karunasagar, Indrani; Boon, Nico; Bossier, Peter

2010-02-01

Quorum sensing, bacterial cell-to-cell communication, regulates the virulence of Vibrio harveyi towards different hosts. Chitinase can be considered as a virulence factor because it helps pathogenic bacteria to attach to the host and to penetrate its tissues (e.g. in case of shrimp). Here, we show that quorum sensing negatively regulates chitinase in V. harveyi. Chitinolytic activity towards natural chitin from crab shells, the synthetic chitin derivative chitin azure, and fluorogenic chitin oligomers was significantly higher in a mutant in which the quorum-sensing system is completely inactivated when compared with a mutant in which the system is maximally active. Furthermore, the addition of signal molecule containing cell-free culture fluids decreased chitinase activity in a Harveyi Autoinducer 1 and Autoinducer 2-deficient double mutant. Finally, chitinase A mRNA levels were fivefold lower in the mutant in which the quorum-sensing system is maximally active when compared with the mutant in which the system is completely inactivated. [Correction added on 25 September 2009, after first online publication: the preceding sentence was corrected from 'Finally, chitinase A mRNA levels were fivefold lower in the mutant in which the quorum-sensing system is completely inactivated when compared with the mutant in which the system is maximally active.'] We argue that this regulation might help the vibrios to switch between host-associated and free-living life styles. © 2009 Society for Applied Microbiology and Blackwell Publishing Ltd.

26183 - Royal Decree 2519/1982 of 12 August approving the Regulations on Protection Against Ionizing Radiation

International Nuclear Information System (INIS)

1981-01-01

This Royal Decree approves the Regulations on Protection against Ionizing Radiation. The purpose of the Regulations is to implement the radiation protection principles laid down in the framework Act on Nuclear Energy of 29th April 1964, as amended. They supersede all existing national rules in the same field and contain administrative and technical provisions governing nuclear and radioactive installations and activities, including the use of radiation-emitting equipment. They were made in compliance with the most recent international regulations on radiation protection and safety, in particular the Recommendations of the International Atomic Energy Agency (IAEA); the Regulations also take into account the recent Euratom Directives. (NEA) [fr

Mothering, fathering, and the regulation of negative and positive emotions in high-functioning preschoolers with autism spectrum disorder.

Science.gov (United States)

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

Impaired down-regulation of negative emotion in self-referent social situations in bipolar disorder

DEFF Research Database (Denmark)

Kjærstad, Hanne L; Vinberg, Maj; Goldin, Philippe R

2016-01-01

naturally or dampen their emotional response to positive and negative social scenarios and associated self-beliefs. They were also given an established experimental task for comparison, involving reappraisal of negative affective picture stimuli, as well as a questionnaire of habitual ER strategies. BD...... patients showed reduced ability to down-regulate emotional responses in negative, but not positive, social scenarios relative to healthy controls and UD patients. In contrast, there were no between-group differences in the established ER task or in self-reported habitual reappraisal strategies. Findings...

Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein

International Nuclear Information System (INIS)

Lee, Na-Rae; Shin, Han-Bo; Kim, Hye-In; Choi, Myung-Soo; Inn, Kyung-Soo

2013-01-01

Highlights: •TRK-fused gene product (TFG) interacts with TRIM25 upon viral infection. •TFG negatively regulates RIG-I mediated antiviral signaling. •TFG depletion leads to enhanced viral replication. •TFG act downstream of MAVS. -- Abstract: RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediated IFN production and nuclear factor (NF)-κB signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways

Soil structural quality assessment for soil protection regulation

Science.gov (United States)

Johannes, Alice; Boivin, Pascal

2017-04-01

Soil quality assessment is rapidly developing worldwide, though mostly focused on the monitoring of arable land and soil fertility. Soil protection regulations assess soil quality differently, focusing on priority pollutants and threshold values. The soil physical properties are weakly considered, due to lack of consensus and experimental difficulties faced with characterization. Non-disputable, easy to perform and inexpensive methods should be available for environmental regulation to be applied, which is unfortunately not the case. As a consequence, quantitative soil physical protection regulation is not applied, and inexpensive soil physical quality indicators for arable soil management are not available. Overcoming these limitations was the objective of a research project funded by the Swiss federal office for environment (FOEN). The main results and the perspectives of application are given in this presentation. A first step of the research was to characterize soils in a good structural state (reference soils) under different land use. The structural quality was assessed with field expertise and Visual Evaluation of the Soil Structure (VESS), and the physical properties were assessed with Shrinkage analysis. The relationships between the physical properties and the soil constituents were linear and highly determined. They represent the reference properties of the corresponding soils. In a second step, the properties of physically degraded soils were analysed and compared to the reference properties. This allowed defining the most discriminant parameters departing the different structure qualities and their threshold limits. Equivalent properties corresponding to these parameters but inexpensive and easy to determine were defined and tested. More than 90% of the samples were correctly classed with this method, which meets, therefore, the requirements for practical application in regulation. Moreover, result-oriented agri-environmental schemes for soil quality

THE MAIN NOVELTIES AND IMPLICATIONS OF THE NEW GENERAL DATA PROTECTION REGULATION

Directory of Open Access Journals (Sweden)

Simona Chirica

2017-12-01

Full Text Available Regulation (EU 2016/679 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95/46/EC (General Data Protection Regulation - GDPR will become applicable beginning with 25.05.2018. As a general characteristic, the regulations adopted at EU level, have direct applicability in all EU member states, and they are automatically integrated in the national legislation beginning with entry into force. Therefore, as of 25.05.2018, the GDPR provisions will be applicable and mandatory for all natural and legal persons that process personal data, including in Romania. Based on the above, GDPR brings a series of changes affecting all the involved parties (data subjects, data controllers, supervisory authorities. This article aims to present an analysis of the main novelties brought by the new regulation, and to present a comparison with the current regulation together with the practical implications of these changes in relation to the data subjects, data controllers, and supervisory authorities.

Fitting in and standing out: increasing the use of alcohol protective behavioral strategies with a deviance regulation intervention.

Science.gov (United States)

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).

Exercise protects from cancer through regulation of immune function and inflammation

DEFF Research Database (Denmark)

Hojman, Pernille

2017-01-01

Exercise training has been extensively studied in cancer settings as part of prevention or rehabilitation strategies, yet emerging evidence suggests that exercise training can also directly affect tumor-specific outcomes. The underlying mechanisms for this exercise-dependent cancer protection are...... regulation of immune and inflammatory functions, and exercise may be pursued as anticancer treatment through incorporation into standard oncological therapy to the benefit of the cancer patients.......Exercise training has been extensively studied in cancer settings as part of prevention or rehabilitation strategies, yet emerging evidence suggests that exercise training can also directly affect tumor-specific outcomes. The underlying mechanisms for this exercise-dependent cancer protection...... are just starting to be elucidated. To this end, evasion of immune surveillance and tumor-associated inflammation are established as hallmarks of cancer, and exercise may target cancer incidence and progression through regulation of these mechanisms. Here, I review the role of exercise in protection from...

How is emotional awareness related to emotion regulation strategies and self-reported negative affect in the general population?

Science.gov (United States)

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

2014-01-01

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

Regulations under the Radiation Protection and Control Act, 1982, No. 221 of 1984

International Nuclear Information System (INIS)

1984-01-01

These Regulations made under the Radiation Protection and Control Act of 1982, amend several numerical quotations contained in the Radiation Safety (Transport) Regulations, No. 27, 1984, also made under the above mentioned Act. (NEA) [fr

Basis for applying for exemption according to species protection regulation. Final repository for spent nuclear fuel at Forsmark; Underlag till ansoekan om dispens enligt artskyddsfoerordningen. Slutfoervar foer anvaent kaernbraensle i Forsmark

Energy Technology Data Exchange (ETDEWEB)

2011-02-15

SKB will submit applications for permits and admissibility under the Environmental Act and under the Nuclear Activities Act to construct and operate a disposal facility for spent nuclear fuel at Forsmark. In the final repository the spent nuclear fuel from Swedish nuclear power plants is placed in order to protect human health and the environment against harmful effects of ionizing radiation. Construction and operation of the disposal facility in Forsmark will make an impact, give effects and consequences for the natural environment. Utilization of land for the construction of the facility and the impact on ground water as a result of groundwater drainage is expected to have negative consequences for the species included in species protection regulation. Thus, the planned activity require exemption from species protection regulation (SFS 2007:845). The purpose of this document is to provide a basis for an application for exemption under 14 paragraph species protection regulation from the prohibitions of 4, 6, 7 and 8 paragraph species protection regulation. A basis for the exemption application is that the proposed activity is considered to have an 'overriding public interest' prescribed in 14 paragraph species protection regulation. The document reports the impact, effects and consequences of the planned activities on species covered in the species protection regulation. The impact on protected species can be divided into two categories: - Direct effects on protected species and their habitats by utilization of the land. - Indirect effects on protected species and their habitats in the drainage of groundwater and the effect on groundwater levels. The document also includes a description of planned actions to prevent, restrict and compensate for the effects and consequences that the activity may cause. By applying for an exemption under 14 paragraph species protection regulation in a separate order from the application for permit according to chapters 9

Basis for applying for exemption according to species protection regulation. Final repository for spent nuclear fuel at Forsmark; Underlag till ansoekan om dispens enligt artskyddsfoerordningen. Slutfoervar foer anvaent kaernbraensle i Forsmark

Energy Technology Data Exchange (ETDEWEB)

2011-02-15

SKB will submit applications for permits and admissibility under the Environmental Act and under the Nuclear Activities Act to construct and operate a disposal facility for spent nuclear fuel at Forsmark. In the final repository the spent nuclear fuel from Swedish nuclear power plants is placed in order to protect human health and the environment against harmful effects of ionizing radiation. Construction and operation of the disposal facility in Forsmark will make an impact, give effects and consequences for the natural environment. Utilization of land for the construction of the facility and the impact on ground water as a result of groundwater drainage is expected to have negative consequences for the species included in species protection regulation. Thus, the planned activity require exemption from species protection regulation (SFS 2007:845). The purpose of this document is to provide a basis for an application for exemption under 14 paragraph species protection regulation from the prohibitions of 4, 6, 7 and 8 paragraph species protection regulation. A basis for the exemption application is that the proposed activity is considered to have an 'overriding public interest' prescribed in 14 paragraph species protection regulation. The document reports the impact, effects and consequences of the planned activities on species covered in the species protection regulation. The impact on protected species can be divided into two categories: - Direct effects on protected species and their habitats by utilization of the land. - Indirect effects on protected species and their habitats in the drainage of groundwater and the effect on groundwater levels. The document also includes a description of planned actions to prevent, restrict and compensate for the effects and consequences that the activity may cause. By applying for an exemption under 14 paragraph species protection regulation in a separate order from the application for permit according to chapters 9 and 11

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

Science.gov (United States)

Shackman, Jessica E; Pollak, Seth D

2014-11-01

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

Sweden's radiation protection regulations for spent fuel and nuclear waste: Requirements and compliance

International Nuclear Information System (INIS)

Norden, M.; Jensen, M.; Larsson, C.M.; Avila, R.; Bergman, S.S.; Wiebert, A.; Wiklund, A.

2000-01-01

The Swedish regulations on radiation protection in connection with spent fuel and nuclear waste disposal concern protection of human health and the environment. The reasoning behind the regulations is in observance with the Rio declaration, in the sense that they take into consideration sustainable development also in continued presence of multiple sources of radioactive effluents. Optimisation and best available technique are used as methods for risk reduction. For human health, a risk concept is used, whereas for environmental protection, focus is set on protection of biological resources and diversity. Compliance with the health and environmental goals is discussed using generic definition of the environment. The hypothetical outflow from a repository takes place in the different compartments and the resulting spread in doses are discussed and compared to the requirements of the individual dose standard, and other environmental effects are assessed. (author)

Mel-18 negatively regulates stem cell-like properties through downregulation of miR-21 in gastric cancer.

Science.gov (United States)

Wang, Xiao-Feng; Zhang, Xiao-Wei; Hua, Rui-Xi; Du, Yi-Qun; Huang, Ming-Zhu; Liu, Yong; Cheng, Yu Fang; Guo, Wei-Jian

2016-09-27

Mel-18, a polycomb group protein, has been reported to act as a tumor suppressor and be down-regulated in several human cancers including gastric cancer. It was also found that Mel-18 negatively regulates self-renewal of hematopoietic stem cells and breast cancer stem cells (CSCs). This study aimed to clarify its role in gastric CSCs and explore the mechanisms. We found that low-expression of Mel-18 was correlated with poor prognosis and negatively correlated with overexpression of stem cell markers Oct4, Sox2, and Gli1 in 101 gastric cancer tissues. Mel-18 was down-regulated in cultured spheroid cells, which possess CSCs, and overexpression of Mel-18 inhibits cells sphere-forming ability and tumor growth in vivo. Besides, Mel-18 was lower-expressed in ovary metastatic lesions compared with that in primary lesions of gastric cancer, and Mel-18 overexpression inhibited the migration ability of gastric cancer cells. Interestingly, overexpression of Mel-18 resulted in down-regulation of miR-21 in gastric cancer cells and the expression of Mel-18 was negatively correlated with the expression of miR-21 in gastric cancer tissues. Furthermore, miR-21 overexpression partially restored sphere-forming ability, migration potential and chemo-resistance in Mel-18 overexpressing gastric cancer cells. These results suggests Mel-18 negatively regulates stem cell-like properties through downregulation of miR-21 in gastric cancer cells.

Improved wound management by regulated negative pressure-assisted wound therapy and regulated, oxygen- enriched negative pressure-assisted wound therapy through basic science research and clinical assessment

Directory of Open Access Journals (Sweden)

Moris Topaz

2012-01-01

Full Text Available Regulated negative pressure-assisted wound therapy (RNPT should be regarded as a state-of-the-art technology in wound treatment and the most important physical, nonpharmaceutical, platform technology developed and applied for wound healing in the last two decades. RNPT systems maintain the treated wound′s environment as a semi-closed, semi-isolated system applying external physical stimulations to the wound, leading to biological and biochemical effects, with the potential to substantially influence wound-host interactions, and when properly applied may enhance wound healing. RNPT is a simple, safe, and affordable tool that can be utilized in a wide range of acute and chronic conditions, with reduced need for complicated surgical procedures, and antibiotic treatment. This technology has been shown to be effective and safe, saving limbs and lives on a global scale. Regulated, oxygen-enriched negative pressure-assisted wound therapy (RO-NPT is an innovative technology, whereby supplemental oxygen is concurrently administered with RNPT for their synergistic effect on treatment and prophylaxis of anaerobic wound infection and promotion of wound healing. Understanding the basic science, modes of operation and the associated risks of these technologies through their fundamental clinical mechanisms is the main objective of this review.

Protecting individuals against the negative impact of big data : The potential and limitations of the privacy and data protection law approach

NARCIS (Netherlands)

Oostveen, M.A.A.

2018-01-01

This thesis is about the protection of individuals against the negative impact that big data may have on their private lives. Many positive and promising developments result from big data, but the massive collection and use of data also raise a host of issues. In the European Union, the rights to

The impact of the EU general data protection regulation on scientific research.

Science.gov (United States)

Chassang, Gauthier

2017-01-01

The use of personal data is critical to ensure quality and reliability in scientific research. The new Regulation [European Union (EU)] 2016/679 of 27 April 2016 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data [general data protection regulation (GDPR)], repealing Directive 95/46/EC, strengthens and harmonises the rules for protecting individuals' privacy rights and freedoms within and, under certain conditions, outside the EU territory. This new and historic legal milestone both prolongs and updates the EU acquis of the previous Data Protection Directive 95/46/EC. The GDPR fixes both general rules applying to any kind of personal data processing and specific rules applying to the processing of special categories of personal data such as health data taking place in the context of scientific research, this including clinical and translational research areas. This article aims to provide an overview of the new rules to consider where scientific projects include the processing of personal health data, genetic data or biometric data and other kinds of sensitive information whose use is strictly regulated by the GDPR in order to give the main key facts to researchers to adapt their practices and ensure compliance to the EU law to be enforced in May 2018.

Regulations as a Tool to Increase Consumer Protection on the European Retail Payment Market

Directory of Open Access Journals (Sweden)

Janina Harasim

2018-03-01

Full Text Available Aim/purpose - The purpose of the paper is to identify the main areas of customers' threats concerning using financial services and the in-depth review of European industry- -specific consumer regulations concerning current accounts and payments. Design/methodology/approach - Desk research including in-depth analysis of industry- specific consumer regulations referring to current accounts and payment services having the character of EU directives and regulations, European Commission reports, and documents. Findings - The paper shows that consumers' interests are threatened even when they use basic financial services as current account and combined payment instruments. The analysis based on of desk resources has revealed that the regulations give effect to customer protection only if they strictly correspond to defined areas of threats and particular types of risks. Research implications/limitations - The experience of the recent financial crisis proved that the asymmetry of knowledge and information was one of the crucial reasons disrupting customers' position on financial markets. Research findings will help to identify gaps in regulations and develop the quality of further initiatives aimed on informing customers about the implementation of regulations and improving their financial literacy level. Originality/value/contribution - The payment products are rarely discussed in the literature in the context of consumers' protection and financial regulations. This paper contributes to the debate by providing an overview of financial consumer protection issues concerning retail payments.(original abstract

77 FR 48460 - Transportation of Household Goods in Interstate Commerce; Consumer Protection Regulations

Science.gov (United States)

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...

33 CFR 165.1313 - Security zone regulations, tank ship protection, Puget Sound and adjacent waters, Washington

Science.gov (United States)

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...

Chondroitin sulfate addition to CD44H negatively regulates hyaluronan binding

International Nuclear Information System (INIS)

Ruffell, Brian; Johnson, Pauline

2005-01-01

CD44 is a widely expressed cell adhesion molecule that binds hyaluronan, an extracellular matrix glycosaminoglycan, in a tightly regulated manner. This regulated interaction has been implicated in inflammation and tumor metastasis. CD44 exists in the standard form, CD44H, or as higher molecular mass isoforms due to alternative splicing. Here, we identify serine 180 in human CD44H as the site of chondroitin sulfate addition and show that lack of chondroitin sulfate addition at this site enhances hyaluronan binding by CD44. A CD44H-immunoglobulin fusion protein expressed in HEK293 cells, and CD44H expressed in murine L fibroblast cells were modified by chondroitin sulfate, as determined by reduced sulfate incorporation after chondroitinase ABC treatment. Mutation of serine 180 or glycine 181 in CD44H reduced chondroitin sulfate addition and increased hyaluronan binding, indicating that serine 180 is the site for chondroitin sulfate addition in CD44H and that this negatively regulates hyaluronan binding

Self-regulation as a mediator between sibling relationship quality and early adolescents' positive and negative outcomes.

Science.gov (United States)

Padilla-Walker, Laura M; Harper, James M; Jensen, Alexander C

2010-08-01

The current study examined the role of adolescents' self-regulation as a mediator between sibling relationship quality and adolescent outcomes, after controlling for the quality of the parent-child relationship. Participants were 395 families (282 two parent; 113 single parent) with an adolescent child (M age of child at Time 1 = 11.15, SD = .96, 49% female) who took part in [project name masked for blind review] at both Time 1 and Time 2. Path analysis via structural equation modeling suggested that sibling affection was longitudinally and positively related to self-regulation and prosocial behaviors, and negatively related to externalizing behaviors; while sibling hostility was positively, and having a sister was negatively related to internalizing behaviors (in general, paths were stronger for adolescents from two- vs. single-parent families). There was also evidence that adolescents' self-regulation partially mediated the relation between sibling affection and positive and negative adolescent outcomes. The discussion focuses on the importance of continued research examining the mechanisms through which the sibling relationship influences development during adolescence.

The organisation of work and systems of labour market regulation and social protection

DEFF Research Database (Denmark)

Lorenz, Edward; Lundvall, Bengt-Åke

2011-01-01

The paper demonstrates on the basis of date from 15 European countries that there is a close link between the form of labour market regulation and the systems of social protection on the one hand and modes of work organisation and learning on the other hand.......The paper demonstrates on the basis of date from 15 European countries that there is a close link between the form of labour market regulation and the systems of social protection on the one hand and modes of work organisation and learning on the other hand....

CHILDREN'S HEALTH PROTECTION IN INTERSECTORAL CONNECTION

Directory of Open Access Journals (Sweden)

Yu.E. Lapin

2008-01-01

Full Text Available Recently discovered phenomenon of compensatory mechanism of absence of legislative durable national policy in health protection of children is described in this article. This mechanism was developed as a result of evolution of intersect oral connection for the sake of children's health protection. «National family policy», «national policy for the sake of children», «national policy in the field of circulation of narcotic, psychotropic substances and in the field of counteraction to its illegal use», «national policy of Russian federation in the field of education», «national policy in the field of labor relations» perform functions of such compensatory mechanism. Fact of regulation of social relations in the sphere of children's health protection with means of different active directions of national policy is evidence of legal assignment of a number of problems in children's health protection as real subject of policy. The negative feature of this problem is incomplete and fragmentary regulation of relationships in the field of children's health protection. This is the reason, which maintains a status of children's health protection service as passive dirigible object but not an active regulative factor.Key words: children, health, national policy.

Alcohol Consumption and Negative Sex-Related Consequences among College Women: The Moderating Role of Alcohol Protective Behavioral Strategies

Science.gov (United States)

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…

77 FR 36932 - Transportation of Household Goods in Interstate Commerce; Consumer Protection Regulations

Science.gov (United States)

2012-06-20

... use of energy. List of Subjects in 49 CFR Part 375 Advertising, Arbitration, Consumer protection...--TRANSPORTATION OF HOUSEHOLD GOODS IN INTERSTATE COMMERCE; CONSUMER PROTECTION REGULATIONS 0 1. The authority... No. FMCSA-2012-0119] RIN 2126-AB52 Transportation of Household Goods in Interstate Commerce; Consumer...

DMPD: When signaling pathways collide: positive and negative regulation of toll-likereceptor signal transduction. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18631453 When signaling pathways collide: positive and negative regulation of toll-...uction. PubmedID 18631453 Title When signaling pathways collide: positive and neg...l) Show When signaling pathways collide: positive and negative regulation of toll-likereceptor signal transd...likereceptor signal transduction. O'Neill LA. Immunity. 2008 Jul 18;29(1):12-20. (.png) (.svg) (.html) (.csm

Regulations No. 187 of 31 May 1988 amending section 7 of the regulations on protective measures during work involving ionizing radiation

International Nuclear Information System (INIS)

1988-01-01

These regulations amend regulations No. 1157 of 14 Jun 1985 on protective measures during radiation work. Henceforth workers simultaneously exposed to radiation and cytostatic substances must be given special work instructions to secure their safety. (NEA) [fr

Providers’ Liabilities in the New EU Data Protection Regulation: A threat to internet freedoms?

OpenAIRE

SARTOR, Giovanni

2012-01-01

In this paper I shall consider certain aspects of the Proposal for a Data Protection Regulation recently advanced by the EU Commission, which is meant to substitute the existing Data Protection Directive as well as the national laws implementing it. In particular I shall examine how the Regulation addresses host providers’ liabilities and duties with regard to user-generated content. For this purpose, I shall first highlight some developments in web and cloud services, then I shall consider h...

Further European initiatives and regulations concerning radiation protection: drinking water guideline, maximum permissible contamination in food products and feeding stuff

International Nuclear Information System (INIS)

Mundigl, Stefan

2013-01-01

The radiation protection community has observed intensively the development of basic safety standards concerning protection against hazards of ionizing radiation. The new core part of the European radiation protection legislation is complemented by several specialized regulations relevant for radiation protection. Besides the existing regulations in the field of emergency protection the European Commission initiated a drinking water guideline that will be published in the near future. Furthermore the European commission approved a revised regulation concerning the maximum permissible contamination limits for food products and feeding stuff in case of a future nuclear accident. Together with the new radiation protection basic standards a new complete, coherent and modernized European regulation package will be accomplished.

Understanding Noncompliance with Protected Species Regulations in the Northeast USA Gillnet Fishery

Directory of Open Access Journals (Sweden)

Kathryn D Bisack

2015-11-01

Full Text Available Marine mammals and sea turtles in the United States are protected from commercial fishery interactions under the Marine Mammal Protection Act and the Endangered Species Act. To reduce harbor porpoise bycatch in the northeast sink gillnet fishery, fishermen are mandated to attach pingers to their nets in regulated areas. Although, pinger regulations have been in place for over a decade, in practice, enforcement is weak and the penalty for a violation is almost non-existent. In this scenario, the presence of normative factors may motivate a fisherman to comply with the pinger regulation. This study considers both economic and normative factors within a probit framework to explain a fisherman’s compliance decision. Model results indicate fishermen who previously violated pinger regulations, who are not completely dependent on gillnet gear and face a lower chance of being detected by an observer, are more likely to violate. Understanding the influence of normative factors on compliance decisions is a key component for higher compliance. That is, incorporation of these factors in the design of policy instruments may achieve higher compliance rates and thus more success in protecting these species. Our model findings were ground-truthed by conducting focus group research with fishermen using pingers; some preliminary findings are shared in the discussion in support of our model results. Finally, these results also suggest observer data can be used to support compliance and enforcement mechanisms in this fishery and possibly other fisheries as well.

Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway.

Science.gov (United States)

Liu, Yunxia; Dong, Weibing; Shao, Jing; Wang, Yibin; Zhou, Meiyi; Sun, Haipeng

2017-01-01

Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA.Interestingly, BCAA starvation induced PI3K-AKT signaling. KLF15 induction by BCAA starvation was blocked by PI3K and AKT inhibitors, indicating the activation of PI3K-AKT signaling pathway mediated the KLF15 induction. BCAA regulated KLF15 expression at transcriptional level but not post-transcriptional level. However, BCAA starvation failed to increase the KLF15-promoter-driven luciferase expression, suggesting KLF15 promoter activity was not directly controlled by BCAA. Finally, fasting reduced BCAA abundance in mice and KLF15 expression was dramatically induced in muscle and white adipose tissue, but not in liver. Together, these data demonstrated BCAA negatively regulated KLF15 expression, suggesting a novel molecular mechanism underlying BCAA's multiple functions in metabolic regulation.

Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway

Directory of Open Access Journals (Sweden)

Yunxia Liu

2017-10-01

Full Text Available Recent studies have linked branched-chain amino acid (BCAA with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15 is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA.Interestingly, BCAA starvation induced PI3K-AKT signaling. KLF15 induction by BCAA starvation was blocked by PI3K and AKT inhibitors, indicating the activation of PI3K-AKT signaling pathway mediated the KLF15 induction. BCAA regulated KLF15 expression at transcriptional level but not post-transcriptional level. However, BCAA starvation failed to increase the KLF15-promoter-driven luciferase expression, suggesting KLF15 promoter activity was not directly controlled by BCAA. Finally, fasting reduced BCAA abundance in mice and KLF15 expression was dramatically induced in muscle and white adipose tissue, but not in liver. Together, these data demonstrated BCAA negatively regulated KLF15 expression, suggesting a novel molecular mechanism underlying BCAA's multiple functions in metabolic regulation.

The regulation of the radiological protection in Mexico; La reglamentacion de la proteccion radiologica en Mexico

Energy Technology Data Exchange (ETDEWEB)

Eibenschutz H, J. [Comision Nacional de Seguridad Nuclear y Salvaguardias, Dr. Jose Ma. Barragan No. 779, Col. Narvarte, 03020 Mexico D. F. (Mexico)

2008-12-15

The regulation antecedents in nuclear question in Mexico are placed in 1950, with the promulgation of {sup L}aw that declares national mining reserves the uranium deposits, thorium and the other substances of which obtains fissionable isotopes that can produce nuclear energy{sup ,} instrument that stipulated the control of uranium, thorium, as to its it indicated it name, and other fissionable substances, on the part of the state, although they were without a doubt the respective institutions, the National Commission of Nuclear Energy in 1955, and the one of the National Commission of Nuclear Safety and Safeguards (CNSNS) in 1979, those that allowed the development of a prescribed frame in the nuclear and radiological areas. One characteristic of the regulation in radiological protection is the variety in the authorities type that have incidence in the regulation, as a result of the different approaches with which it can be approached. For example, in Mexico normative instruments with content in radiological protection exist and are watched over the Health Secretary, who is oriented to the protection of the patient, their relatives and the medical body; Work and Social Welfare Secretary, with a labor approach; Communications and Transport Secretary, which regulates the transport of nuclear and radioactive materials; Finance and Public Credit Secretary, who regulates the import and export of radioactive materials; Environment and Natural Resources Secretary, which regulates the environment protection; Energy Secretary who has responsibilities inside of the {sup p}rescribed law of article 27 constitutional in nuclear matter{sup ;} and within the energy sector, the CNSNS that expedite and watch the fulfillment of normative in radiological protection and nuclear safety. In order to resist effects of on regulation; frequently inter institutional agreements are carried out in which the areas of monitoring are agreed by each authority. The regulation in radiological

Client Violence and Its Negative Impacts on Work Attitudes of Child Protection Workers Compared to Community Service Workers

Science.gov (United States)

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…

Some aspects in the compliance with the Japanese radiation protection regulations

International Nuclear Information System (INIS)

Yamamoto, Hideaki; Mizushita, Seiichi

2007-01-01

This paper gives an overview of the major subjects in the recent amendments to the Japanese radiation protection regulations. These are related to the scope of the application of regulations: exclusion, exemption and clearance. The Radiological Hazards Prevention Law has modified the legal definition of 'radioactive materials'. The Reactors Control Law has been amended to establish clearance levels for releasing radioactive materials from regulatory control. The Japanese government has a plan to develop guidelines for exclusion and exemption of certain types of naturally-occurring radioactive materials (NORM). Some aspects in the compliance with the regulations are addressed. (author)

fundTPL-2 – ERK1/2 Signaling Promotes Host Resistance against Intracellular Bacterial Infection by Negative Regulation of Type I Interferon Production3

Science.gov (United States)

McNab, Finlay W.; Ewbank, John; Rajsbaum, Ricardo; Stavropoulos, Evangelos; Martirosyan, Anna; Redford, Paul S.; Wu, Xuemei; Graham, Christine M.; Saraiva, Margarida; Tsichlis, Philip; Chaussabel, Damien; Ley, Steven C.; O’Garra, Anne

2013-01-01

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of mortality and morbidity worldwide, causing approximately 1.4 million deaths per year. Key immune components for host protection during tuberculosis include the cytokines IL-12, IL-1 and TNF-α, as well as IFN-γ and CD4+ Th1 cells. However, immune factors determining whether individuals control infection or progress to active tuberculosis are incompletely understood. Excess amounts of type I interferon have been linked to exacerbated disease during tuberculosis in mouse models and to active disease in patients, suggesting tight regulation of this family of cytokines is critical to host resistance. In addition, the immunosuppressive cytokine IL-10 is known to inhibit the immune response to Mtb in murine models through the negative regulation of key pro-inflammatory cytokines and the subsequent Th1 response. We show here, using a combination of transcriptomic analysis, genetics and pharmacological inhibitors that the TPL-2-ERK1/2 signaling pathway is important in mediating host resistance to tuberculosis through negative regulation of type I interferon production. The TPL-2-ERK1/2 signalling pathway regulated production by macrophages of several cytokines important in the immune response to Mtb as well as regulating induction of a large number of additional genes, many in a type I IFN dependent manner. In the absence of TPL-2 in vivo, excess type I interferon promoted IL-10 production and exacerbated disease. These findings describe an important regulatory mechanism for controlling tuberculosis and reveal mechanisms by which type I interferon may promote susceptibility to this important disease. PMID:23842752

Negative regulation of Toll-like receptor signaling plays an essential role in homeostasis of the intestine.

Science.gov (United States)

Biswas, Amlan; Wilmanski, Jeanette; Forsman, Huamei; Hrncir, Tomas; Hao, Liming; Tlaskalova-Hogenova, Helena; Kobayashi, Koichi S

2011-01-01

A healthy intestinal tract is characterized by controlled homeostasis due to the balanced interaction between commensal bacteria and the host mucosal immune system. Human and animal model studies have supported the hypothesis that breakdown of this homeostasis may underlie the pathogenesis of inflammatory bowel diseases. However, it is not well understood how intestinal microflora stimulate the intestinal mucosal immune system and how such activation is regulated. Using a spontaneous, commensal bacteria-dependent colitis model in IL-10-deficient mice, we investigated the role of TLR and their negative regulation in intestinal homeostasis. In addition to IL-10(-/-) MyD88(-/-) mice, IL-10(-/-) TLR4(-/-) mice exhibited reduced colitis compared to IL-10(-/-) mice, indicating that TLR4 signaling plays an important role in inducing colitis. Interestingly, the expression of IRAK-M, a negative regulator of TLR signaling, is dependent on intestinal commensal flora, as IRAK-M expression was reduced in mice re-derived into a germ-free environment, and introduction of commensal bacteria into germ-free mice induced IRAK-M expression. IL-10(-/-) IRAK-M(-/-) mice exhibited exacerbated colitis with increased inflammatory cytokine gene expression. Therefore, this study indicates that intestinal microflora stimulate the colitogenic immune system through TLR and negative regulation of TLR signaling is essential in maintaining intestinal homeostasis. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evidence for the negative impact of reward on self-regulated learning.

Science.gov (United States)

Wehe, Hillary S; Rhodes, Matthew G; Seger, Carol A

2015-01-01

The undermining effect refers to the detrimental impact rewards can have on intrinsic motivation to engage in a behaviour. The current study tested the hypothesis that participants' self-regulated learning behaviours are susceptible to the undermining effect. Participants were assigned to learn a set of Swahili-English word pairs. Half of the participants were offered a reward for performance, and half were not offered a reward. After the initial study phase, participants were permitted to continue studying the words during a free period. The results were consistent with an undermining effect: Participants who were not offered a reward spent more time studying the words during the free period. The results suggest that rewards may negatively impact self-regulated learning behaviours and provide support for the encouragement of intrinsic motivation.

Implementation of the General Data Protection Regulation in companies in the Republic of Croatia

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Krešimir Starčević

2018-01-01

Full Text Available This paper deals with the current issue of protecting individuals regarding the processing of their personal data and the free movement of such data. As this matter is also regulated by the European Union legislation, the paper describes and analyzes the scope, implications, methods and tools for applying the new EU regulation adopted on 27 April 2016 by the Parliament and the Council of the European Union. The subject matter is the Regulation (EU 2016/679 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data. The short title of this Regulation is General Data Protection Regulation (GDPR. The term GDPR is thus in common everyday use in companies and among business people, and will also be used in this paper. In addition, the paper analyzes the research conducted on the existing state of affairs and the way in which all collected personal data are processed and used by all stakeholders in the company Atlantic Grupa d.d., Zagreb. In addition, a harmonized project of a structured and methodologically correct procedure for implementation of the provisions of the new Regulation is described for the purpose of achieving the highest degree of compliance of all members of Atlantic Grupa d.d. with the provisions of the GDPR. Finally, the basic objective of the described project is explained, which is to avoid situations that would lead to the extremely high fines for non-compliance with the Regulation.

HDAC3 Is a Critical Negative Regulator of Long-Term Memory Formation

Science.gov (United States)

McQuown, Susan C.; Barrett, Ruth M.; Matheos, Dina P.; Post, Rebecca J.; Rogge, George A.; Alenghat, Theresa; Mullican, Shannon E.; Jones, Steven; Rusche, James R.; Lazar, Mitchell A.; Wood, Marcelo A.

2011-01-01

Gene expression is dynamically regulated by chromatin modifications on histone tails, such as acetylation. In general, histone acetylation promotes transcription, whereas histone deacetylation negatively regulates transcription. The interplay between histone acetyl-transerases and histone deacetylases (HDACs) is pivotal for the regulation of gene expression required for long-term memory processes. Currently, very little is known about the role of individual HDACs in learning and memory. We examined the role of HDAC3 in long-term memory using a combined genetic and pharmacologic approach. We used HDAC3–FLOX genetically modified mice in combination with adeno-associated virus-expressing Cre recombinase to generate focal homozygous deletions of Hdac3 in area CA1 of the dorsal hippocampus. To complement this approach, we also used a selective inhibitor of HDAC3, RGFP136 [N-(6-(2-amino-4-fluorophenylamino)-6-oxohexyl)-4-methylbenzamide]. Immunohistochemistry showed that focal deletion or intrahippocampal delivery of RGFP136 resulted in increased histone acetylation. Both the focal deletion of HDAC3 as well as HDAC3 inhibition via RGFP136 significantly enhanced long-term memory in a persistent manner. Next we examined expression of genes implicated in long-term memory from dorsal hippocampal punches using quantitative reverse transcription-PCR. Expression of nuclear receptor subfamily 4 group A, member 2 (Nr4a2) and c-fos was significantly increased in the hippocampus of HDAC3–FLOX mice compared with wild-type controls. Memory enhancements observed in HDAC3–FLOX mice were abolished by intrahippocampal delivery of Nr4a2 small interfering RNA, suggesting a mechanism by which HDAC3 negatively regulates memory formation. Together, these findings demonstrate a critical role for HDAC3 in the molecular mechanisms underlying long-term memory formation. PMID:21228185

New requirements embodied in expert knowledge regulations for industrial radiation protection officers

International Nuclear Information System (INIS)

Vogt, H.G.

2001-01-01

Expert knowledge standards and certification requirements of health physics responsible persons or radiation safety officers in industry or in health care are laid down in Germany in administrative regulations. Now the new Radiation Protection Ordinance (StrlSchV) contains a specific section exclusively devoted to all aspects of expert knowledge in industrial radiation protection, which inter alia demonstrates the special significance of education and further training of radiation protection specialists. It is expected that the forthcoming new X-ray Ordinance (RoeV) will contain a similar amendment. The article explains the implications of the new Radiation Protection Ordinance for the education and further training of industrial radiation protection officers, but does not address specific aspects of nuclear engineering. (orig./CB) [de

Interleukin-17 receptor A (IL-17RA) as a central regulator of the protective immune response against Giardia.

Science.gov (United States)

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.

Mindfulness in schizophrenia: Associations with self-reported motivation, emotion regulation, dysfunctional attitudes, and negative symptoms.

Science.gov (United States)

Tabak, Naomi T; Horan, William P; Green, Michael F

2015-10-01

Mindfulness-based interventions are gaining empirical support as alternative or adjunctive treatments for a variety of mental health conditions, including anxiety, depression, and substance use disorders. Emerging evidence now suggests that mindfulness-based treatments may also improve clinical features of schizophrenia, including negative symptoms. However, no research has examined the construct of mindfulness and its correlates in schizophrenia. In this study, we examined self-reported mindfulness in patients (n=35) and controls (n=25) using the Five-Facet Mindfulness Questionnaire. We examined correlations among mindfulness, negative symptoms, and psychological constructs associated with negative symptoms and adaptive functioning, including motivation, emotion regulation, and dysfunctional attitudes. As hypothesized, patients endorsed lower levels of mindfulness than controls. In patients, mindfulness was unrelated to negative symptoms, but it was associated with more adaptive emotion regulation (greater reappraisal) and beliefs (lower dysfunctional attitudes). Some facets of mindfulness were also associated with self-reported motivation (behavioral activation and inhibition). These patterns of correlations were similar in patients and controls. Findings from this initial study suggest that schizophrenia patients may benefit from mindfulness-based interventions because they (a) have lower self-reported mindfulness than controls and (b) demonstrate strong relationships between mindfulness and psychological constructs related to adaptive functioning. Copyright © 2015 Elsevier B.V. All rights reserved.

Whistleblowing in the Slovak labor law regulation

Directory of Open Access Journals (Sweden)

Daniel Krošlák

2015-12-01

Full Text Available Corrupt behaviour is a common practice with negative effects on the whole of society. For instance, if a company wins a public procurement contract in an unfair way, it enriches itself not only at the expense of competition, but also at the expense of the whole of society, as the best applicant has not necessarily been selected within such a procurement. The same applies in the case of a supplier launching an unsafe product onto the market, threatening the health of everyone who buys it. In order to prevent such malpractice and eliminate their negative effects, the cooperation of persons aware of such behaviours is necessary. In order to ensure such cooperation, however, the existence of instruments protecting whistle-blowers against various sanctions (especially by employers is necessary. As Slovak legislation did not include a regulation of procedures for reporting malpractice and protecting whistle-blowers, a new law aimed at solving such issues was enacted in October, 2014. The given legal regulation took effect on January 1, 2015. This paper endeavours to provide basic knowledge of the environment that the given regulation entered, as well as information on the possibilities of individuals to protect social interests on its grounds.

Analysis of the regulation on protective and remedial measures on the radioactive contaminated territories

International Nuclear Information System (INIS)

Kutkov, V.A.; Demin, V.F.; Vasiliev, A.; Ivanov, E.; Tsyb, A.

2002-01-01

The current regulation and decisions on the radiation and social protection and rehabilitation of the radioactive contaminated territories are analyzed with purpose to learn all lessons needed for improvement of the regulation and activity in restoration phase and in the preparedness to possible future radiological accidents. Necessity to go beyond the simple radiation protection approach in the decision making and to use risk analysis considering both radiological and non-radiological factors is one of the lessons. The conceptual aspects of risk analysis together with dose assessment in decision making are considered. (author)

Plexin-B2 negatively regulates macrophage motility, Rac, and Cdc42 activation.

Directory of Open Access Journals (Sweden)

Kelly E Roney

Full Text Available Plexins are cell surface receptors widely studied in the nervous system, where they mediate migration and morphogenesis though the Rho family of small GTPases. More recently, plexins have been implicated in immune processes including cell-cell interaction, immune activation, migration, and cytokine production. Plexin-B2 facilitates ligand induced cell guidance and migration in the nervous system, and induces cytoskeletal changes in overexpression assays through RhoGTPase. The function of Plexin-B2 in the immune system is unknown. This report shows that Plexin-B2 is highly expressed on cells of the innate immune system in the mouse, including macrophages, conventional dendritic cells, and plasmacytoid dendritic cells. However, Plexin-B2 does not appear to regulate the production of proinflammatory cytokines, phagocytosis of a variety of targets, or directional migration towards chemoattractants or extracellular matrix in mouse macrophages. Instead, Plxnb2(-/- macrophages have greater cellular motility than wild type in the unstimulated state that is accompanied by more active, GTP-bound Rac and Cdc42. Additionally, Plxnb2(-/- macrophages demonstrate faster in vitro wound closure activity. Studies have shown that a closely related family member, Plexin-B1, binds to active Rac and sequesters it from downstream signaling. The interaction of Plexin-B2 with Rac has only been previously confirmed in yeast and bacterial overexpression assays. The data presented here show that Plexin-B2 functions in mouse macrophages as a negative regulator of the GTPases Rac and Cdc42 and as a negative regulator of basal cell motility and wound healing.

Arabidopsis phosphoinositide-specific phospholipase C 4 negatively regulates seedling salt tolerance.

Science.gov (United States)

Xia, Keke; Wang, Bo; Zhang, Jiewei; Li, Yuan; Yang, Hailian; Ren, Dongtao

2017-08-01

Previous physiological and pharmacological studies have suggested that the activity of phosphoinositide-specific phospholipase C (PI-PLC) plays an important role in regulating plant salt stress responses by altering the intracellular Ca 2+ concentration. However, the individual members of plant PLCs involved in this process need to be identified. Here, the function of AtPLC4 in the salt stress response of Arabidopsis seedlings was analysed. plc4 mutant seedlings showed hyposensitivity to salt stress compared with Col-0 wild-type seedlings, and the salt hyposensitive phenotype could be complemented by the expression of native promoter-controlled AtPLC4. Transgenic seedlings with AtPLC4 overexpression (AtPLC4 OE) exhibited a salt-hypersensitive phenotype, while transgenic seedlings with its inactive mutant expression (AtPLC4m OE) did not exhibit this phenotype. Using aequorin as a Ca 2+ indicator in plc4 mutant and AtPLC4 OE seedlings, AtPLC4 was shown to positively regulate the salt-induced Ca 2+ increase. The salt-hypersensitive phenotype of AtPLC4 OE seedlings was partially rescued by EGTA. An analysis of salt-responsive genes revealed that the transcription of RD29B, MYB15 and ZAT10 was inversely regulated in plc4 mutant and AtPLC4 OE seedlings. Our findings suggest that AtPLC4 negatively regulates the salt tolerance of Arabidopsis seedlings, and Ca 2+ may be involved in regulating this process. © 2017 John Wiley & Sons Ltd.

Converting the GSR part3 into a national regulations for the protection and safety of radiation sources

International Nuclear Information System (INIS)

Hatim, Abdulrahman

2016-04-01

The achievement and maintenance of a high level of Radiation Protection and Safety of Radiation Sources depends on a sound legal and governmental infrastructure, including a regulatory body with well-defined responsibilities and functions. The project aimed at converting the IAEA GRS Part 3 into National regulations in Sudan for the protection against the harmful effects of ionizing radiation and safety of radiation sources. The regulations developed covered general requirements for radiation protection, verification of safety, planned exposure situations, emergency exposure situations and existing exposure situation. The Government of Sudan is expected to empower the Sudanese Nuclear Radiological Regulatory Authority (SNRAA) and other relevant authorities to undertake the conversion of IAEA GSR Part 3 into national regulations to be used to regulate all facilities and activities in Sudan. (au)

A Loss-of-Function Screen for Phosphatases that Regulate Neurite Outgrowth Identifies PTPN12 as a Negative Regulator of TrkB Tyrosine Phosphorylation

DEFF Research Database (Denmark)

Ambjørn, Malene; Dubreuil, Véronique; Miozzo, Federico

2013-01-01

Alterations in function of the neurotrophin BDNF are associated with neurodegeneration, cognitive decline, and psychiatric disorders. BDNF promotes axonal outgrowth and branching, regulates dendritic tree morphology and is important for axonal regeneration after injury, responses that largely....... This approach identified phosphatases from diverse families, which either positively or negatively modulate BDNF-TrkB-mediated neurite outgrowth, and most of which have little or no previously established function related to NT signaling. "Classical" protein tyrosine phosphatases (PTPs) accounted for 13......% of the candidate regulatory phosphatases. The top classical PTP identified as a negative regulator of BDNF-TrkB-mediated neurite outgrowth was PTPN12 (also called PTP-PEST). Validation and follow-up studies showed that endogenous PTPN12 antagonizes tyrosine phosphorylation of TrkB itself, and the downstream...

A Longitudinal Study of Emotion Regulation, Emotion Lability-Negativity, and Internalizing Symptomatology in Maltreated and Nonmaltreated Children

Science.gov (United States)

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…

Orphan Nuclear Receptor ERRα Controls Macrophage Metabolic Signaling and A20 Expression to Negatively Regulate TLR-Induced Inflammation.

Science.gov (United States)

Yuk, Jae-Min; Kim, Tae Sung; Kim, Soo Yeon; Lee, Hye-Mi; Han, Jeongsu; Dufour, Catherine Rosa; Kim, Jin Kyung; Jin, Hyo Sun; Yang, Chul-Su; Park, Ki-Sun; Lee, Chul-Ho; Kim, Jin-Man; Kweon, Gi Ryang; Choi, Hueng-Sik; Vanacker, Jean-Marc; Moore, David D; Giguère, Vincent; Jo, Eun-Kyeong

2015-07-21

The orphan nuclear receptor estrogen-related receptor α (ERRα; NR3B1) is a key metabolic regulator, but its function in regulating inflammation remains largely unknown. Here, we demonstrate that ERRα negatively regulates Toll-like receptor (TLR)-induced inflammation by promoting Tnfaip3 transcription and fine-tuning of metabolic reprogramming in macrophages. ERRα-deficient (Esrra(-/-)) mice showed increased susceptibility to endotoxin-induced septic shock, leading to more severe pro-inflammatory responses than control mice. ERRα regulated macrophage inflammatory responses by directly binding the promoter region of Tnfaip3, a deubiquitinating enzyme in TLR signaling. In addition, Esrra(-/-) macrophages showed an increased glycolysis, but impaired mitochondrial respiratory function and biogenesis. Further, ERRα was required for the regulation of NF-κB signaling by controlling p65 acetylation via maintenance of NAD(+) levels and sirtuin 1 activation. These findings unravel a previously unappreciated role for ERRα as a negative regulator of TLR-induced inflammatory responses through inducing Tnfaip3 transcription and controlling the metabolic reprogramming. Copyright © 2015 Elsevier Inc. All rights reserved.

International recommendations on scope of radiological protection regulations - ICRP Publication 104

International Nuclear Information System (INIS)

Stanescu, Gabriel; Avadanei, Camelia; Ghilea, Simion

2011-01-01

The system of radiological protection applies, in principle, to all exposures to ionising radiation. Nevertheless, in practice, the measures taken in order to control these exposures should be limited for pragmatic reasons. ICRP Publication 104 deals with the scope of radiological protection control measures and describes the instruments that can be used for this purpose: exclusion, exemption, clearance. This paper aims to present the ICRP recommendations on scope of regulations in all types of exposure situations: planned, emergency and existing. Also, there are discussed the instruments available to regulators in different exposure situations. Exclusion refers to the deliberate omission of exposure situations from the scope of regulatory requirements, and exemption refers to waiving regulatory requirements if their application is not warranted. A special case of exemption, termed 'clearance', refers to the relinquishing of regulatory control if such a control becomes unwarranted. Societal attitudes to the control of exposure situations are taken into account in determining what can be excluded or exempted from regulatory control. People have higher demands for controlling 'artificial' exposure situations than for dealing with 'natural' exposure situations. Therefore, account should be taken not only of the justification and optimisation of controlling measures, but also of the different expectations of those affected by the exposure situations. The recommendations in this report are intended to assist in defining what needs to be the subject of regulatory requirements for radiological protection and what does not. The application of regulatory controls should achieve a net benefit in protection; otherwise, regulatory control is not justified. Similarly, regulatory requirements should be applied in a manner that optimises protection, otherwise the application of regulatory requirements is not warranted. (authors)

Statutory Instruments No 144 of 1994. European Communities (Protection of outside workers from ionising radiation) Regulations, 1994

International Nuclear Information System (INIS)

1994-04-01

These Regulations implement Council Directive 90/641 EURATOM of 4 December, 1990 on the operational protection of outside workers exposed to the risk of ionising radiation during their activities in controlled areas. The Regulations provide for the radiation protection of workers liable to receive an exposure of high radiation levels while working away from their employers' premises. The Regulations also apply to workers who come from, or who go to work in, another Member State of the European Community

Maternal Self-Regulation, Relationship Adjustment, and Home Chaos: Contributions to Infant Negative Emotionality

Science.gov (United States)

Bridgett, David J.; Burt, Nicole M.; Laake, Lauren M.; Oddi, Kate B.

2013-01-01

There has been increasing interest in the direct and indirect effects of parental self-regulation on children’s outcomes. In the present investigation, the effects of maternal self-regulation, home chaos, and inter-parental relationship adjustment on broad and specific indicators of infant negative emotionality (NE) were examined. A sample of maternal caregivers and their 4-month-old infants (N = 85) from a rural community participated. Results demonstrated that better maternal self-regulation was associated with lower infant NE broadly, as well as with lower infant sadness and distress to limitations/frustration and better falling reactivity (i.e. emotion regulation), specifically. Maternal self-regulation also predicted less chaotic home environments and better maternal inter-parental relationship adjustment. Findings also supported the indirect effects of maternal self-regulation on broad and specific indicators of infant NE through home chaos and maternal relationship adjustment. Some differential effects were also identified. Elevated home chaos appeared to specifically affect infant frustration/distress to limitations whereas maternal relationship adjustment affected broad infant NE, as well as several specific indicators of infant NE: frustration/distress to limitations, sadness, and falling reactivity. In conjunction with other recent investigations that have reported the effects of maternal self-regulation on parenting, the findings in the present investigation suggest that parental self-regulation may influence children’s outcomes through several proximal environmental pathways. PMID:23748168

Digitalising the General Data Protection Regulation with Dynamic Condition Response Graphs

DEFF Research Database (Denmark)

Heuck, Emil; Hildebrandt, Thomas; Kiærulff Lerche, Rasmus

2017-01-01

We describe how the declarative Dynamic Condition Response (DCR) Graphs proces notation can be used to digitalise the General Data Protection Regulation (GDPR) and make a first evaluation to what extend the formalisation and associated tool for end-user modelling and simulation can be used to cla...

The executive regulations of the decree-law no. 31 of the year 2002 concerning radiation protection

International Nuclear Information System (INIS)

2002-01-01

The Radiation Protection Laws No.31 of the year 2002 of the State of Qatar is composed of five parts. Part 1 includes articles dealing with definition of terms (Chapter 1) and application and scope of the regulations (Chapter 2). Part 2 deals with licensing (Chapter 1) and inspections aspects (Chapter 2) of the regulations. Article 1 defines legal terms and radiation protection concepts in the context of this regulation. Article 2 describes practices that are covered by these regulations which include: 1. production of radiation sources; extraction and treatment of radioactive raw materials; and use of radiation or radioactive materials for medical, industrial, agricultural, training or scientific research purposes or others, including any activities relating to such use and involve or may involve radiation exposure; 2. practices involving natural sources of radiation which lead to greater dose than that prescribed for workers or the public, and which cannot be ignored from the perspective of radiation protection; 3. any other practice to be determined by the Council and which involves risks from: occupational exposure, medical exposure, public exposure, potential exposure, chronic exposure, or emergency exposure; and intervention in case of an emergency radiation or chronic exposure. Article 3 defines practices that are exempted from the requirements set out in these Regulations. Article 4, 5 and 6 deal with the principles of protection, dose limits and ideal protection and safety. Part 3 consists of 3 chapters: Chapter 1 describes Occupational Exposure Protection and Radiation Work Places, Chapter 2 describes Medical Exposure Protection and Chapter 3 describes Public Exposure. Part 4, consists of 3 chapters: Chapter 1 describes General Requirements For Safety Management and Performance, Chapter 2 describes Radiation Sources Safety and Accidents, and Chapter 3 describes Safe Transport of Radioactive Materials. Part 5 consists of 2 chapters: Chapter 1 describes

Level of compliance with the radiation protection regulation-A survey among Norwegian hospitals and X-ray institutes

International Nuclear Information System (INIS)

Friberg, E. G.; Widmark, A.; Solberg, M.; Woehni, T.

2011-01-01

To identify the level of compliance with the new radiation protection regulation among Norwegian health care enterprises (HCEs). Totally, 41 HCEs were authorised to use advanced X-ray equipment for medical purposes during 2005-07. Follow-up inspections with 14 HCEs were carried out during 2007-09. Main topics for the inspections were those requirements identified as most challenging to implement in the authorisation process. Totally, 192 non-conformities with the regulation were revealed during the authorisation process. The inspections revealed that 93 % of the inspected HCEs had non-conformities with the regulation. Most common non-conformities dealt with skills in radiation protection, establishment of local diagnostic reference levels, access to medical physicists and performance of quality control of X-ray equipment. Inspections are an effective tool for implementation of regulation the requirements at the HCEs, thus improving radiation protection awareness. (authors)

miR-367 promotes proliferation and invasion of hepatocellular carcinoma cells by negatively regulating PTEN

Energy Technology Data Exchange (ETDEWEB)

Meng, Xiangrui, E-mail: mengxiangruibb2008@163.com [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Lu, Peng [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Fan, Qingxia [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China)

2016-01-29

MicroRNAs play important roles in the carcinogenesis of many types of cancers by inhibiting gene expression at posttranscriptional level. However, the roles of microRNAs in hepatocellular carcinoma, are still unclear. Here, we identified that miR-367 promotes hepatocellular carcinoma (HCC) cell proliferation by negatively regulates its target gene PTEN. The expression of miR-367 and PTEN are significantly inverse correlated in 35 HCC patients. In HCC cell line, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-367, while miR-367 inhibitor significantly inhibited the cell proliferation. Transwell assay showed that miR-367 mimics significantly promoted the migration and invasion of HCC cells, whereas miR-367 inhibitors significantly reduced cell migration and invasion. Luciferase assays confirmed that miR-367 directly bound to the 3'untranslated region of PTEN, and western blotting showed that miR-367 suppressed the expression of PTEN at the protein levels. This study indicated that miR-367 negatively regulates PTEN and promotes proliferation and invasion of HCC cells. Thus, miR-367 may represent a potential therapeutic target for HCC intervention. - Highlights: • miR-367 mimics promote the proliferation and invasion of HCC cells. • miR-367 inhibitors inhibit the proliferation and invasion of HCC cells. • miR-367 targets 3′UTR of PTEN in HCC cells. • miR-367 negatively regulates PTEN in HCC cells.

Magical thinking in predictions of negative events: Evidence for tempting fate but not for a protection effect

Directory of Open Access Journals (Sweden)

Job van Wolferen

2013-01-01

Full Text Available In this paper we test two hypotheses regarding magical thinking about the perceived likelihood of future events. The first is that people believe that those who ``tempt fate'' by failing to take necessary precautions are more likely to suffer negative outcomes. The second is the ``protection effect'', where reminding people of precautions they have taken leads them to see related risks as less likely. To this end, we describe the results from three attempted direct replications of a protection effect experiment reported in Tykocinski (2008 and two replications of a tempting fate experiment reported in Risen and Gilovich (2008 in which we add a test of the protection effect. We did not replicate the protection effect but did replicate the tempting fate effect.

Vitamin a is a negative regulator of osteoblast mineralization.

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Thomas Lind

Full Text Available An excessive intake of vitamin A has been associated with an increased risk of fractures in humans. In animals, a high vitamin A intake leads to a reduction of long bone diameter and spontaneous fractures. Studies in rodents indicate that the bone thinning is due to increased periosteal bone resorption and reduced radial growth. Whether the latter is a consequence of direct effects on bone or indirect effects on appetite and general growth is unknown. In this study we therefore used pair-feeding and dynamic histomorphometry to investigate the direct effect of a high intake of vitamin A on bone formation in rats. Although there were no differences in body weight or femur length compared to controls, there was an approximately halved bone formation and mineral apposition rate at the femur diaphysis of rats fed vitamin A. To try to clarify the mechanism(s behind this reduction, we treated primary human osteoblasts and a murine preosteoblastic cell line (MC3T3-E1 with the active metabolite of vitamin A; retinoic acid (RA, a retinoic acid receptor (RAR antagonist (AGN194310, and a Cyp26 inhibitor (R115866 which blocks endogenous RA catabolism. We found that RA, via RARs, suppressed in vitro mineralization. This was independent of a negative effect on osteoblast proliferation. Alkaline phosphatase and bone gamma carboxyglutamate protein (Bglap, Osteocalcin were drastically reduced in RA treated cells and RA also reduced the protein levels of Runx2 and Osterix, key transcription factors for progression to a mature osteoblast. Normal osteoblast differentiation involved up regulation of Cyp26b1, the major enzyme responsible for RA degradation, suggesting that a drop in RA signaling is required for osteogenesis analogous to what has been found for chondrogenesis. In addition, RA decreased Phex, an osteoblast/osteocyte protein necessary for mineralization. Taken together, our data indicate that vitamin A is a negative regulator of osteoblast mineralization.

ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance.

LENUS (Irish Health Repository)

Liu, Jinghua

2010-05-15

Activation of TLR signaling is critical for host innate immunity against bacterial infection. Previous studies reported that the ST2 receptor, a member of the Toll\\/IL-1 receptor superfamily, functions as a negative regulator of TLR4 signaling and maintains LPS tolerance. However, it is undetermined whether ST2 negatively regulates TLR2 signaling and furthermore, whether a TLR2 agonist, bacterial lipoprotein (BLP)-induced tolerance is dependent on ST2. In this study, we show that BLP stimulation-induced production of proinflammatory cytokines and immunocomplex formation of TLR2-MyD88 and MyD88-IL-1R-associated kinase (IRAK) were significantly enhanced in ST2-deficient macrophages compared with those in wild-type controls. Furthermore, overexpression of ST2 dose-dependently attenuated BLP-induced NF-kappaB activation, suggesting a negative regulatory role of ST2 in TLR2 signaling. A moderate but significantly attenuated production of TNF-alpha and IL-6 on a second BLP stimulation was observed in BLP-pretreated, ST2-deficient macrophages, which is associated with substantially reduced IRAK-1 protein expression and downregulated TLR2-MyD88 and MyD88-IRAK immunocomplex formation. ST2-deficient mice, when pretreated with a nonlethal dose of BLP, benefitted from an improved survival against a subsequent lethal BLP challenge, indicating BLP tolerance develops in the absence of the ST2 receptor. Taken together, our results demonstrate that ST2 acts as a negative regulator of TLR2 signaling, but is not required for BLP-induced tolerance.

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

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Won Hee Jung

2010-11-01

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

Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction.

Science.gov (United States)

Yan, Meiping; Zhang, Xinhua; Chen, Ao; Gu, Wei; Liu, Jie; Ren, Xiaojiao; Zhang, Jianping; Wu, Xiaoxiong; Place, Aaron T; Minshall, Richard D; Liu, Guoquan

2017-11-01

Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of leukocytes to endothelial cells and initiates subsequent signaling that promotes their transendothelial migration (TEM). Vascular endothelial (VE)-cadherin plays a critical role in endothelial cell-cell adhesion, thereby controlling endothelial permeability and leukocyte transmigration. This study aimed to determine the molecular signaling events that originate from the ICAM-1-mediated firm adhesion of neutrophils that regulate VE-cadherin's role as a negative regulator of leukocyte transmigration. We observed that ICAM-1 interacts with Src homology domain 2-containing phosphatase-2 (SHP-2), and SHP-2 down-regulation via silencing of small interfering RNA in endothelial cells enhanced neutrophil adhesion to endothelial cells but inhibited neutrophil transmigration. We also found that VE-cadherin associated with the ICAM-1-SHP-2 complex. Moreover, whereas the activation of ICAM-1 leads to VE-cadherin dissociation from ICAM-1 and VE-cadherin association with actin, SHP-2 down-regulation prevented ICAM-1-VE-cadherin association and promoted VE-cadherin-actin association. Furthermore, SHP-2 down-regulation in vivo promoted LPS-induced neutrophil recruitment in mouse lung but delayed neutrophil extravasation. These results suggest that SHP-2- via association with ICAM-1-mediates ICAM-1-induced Src activation and modulates VE-cadherin switching association with ICAM-1 or actin, thereby negatively regulating neutrophil adhesion to endothelial cells and enhancing their TEM.-Yan, M., Zhang, X., Chen, A., Gu, W., Liu, J., Ren, X., Zhang, J., Wu, X., Place, A. T., Minshall, R. D., Liu, G. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction. © FASEB.

Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway

OpenAIRE

Yunxia Liu; Weibing Dong; Jing Shao; Yibin Wang; Meiyi Zhou; Haipeng Sun

2017-01-01

Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively cont...

[Radiation protection. Implications for clinical practice on the new regulations governing roentgen ray irradiation and radioprotection].

Science.gov (United States)

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.

NKG2H-Expressing T Cells Negatively Regulate Immune Responses

Directory of Open Access Journals (Sweden)

Daniela Dukovska

2018-03-01

Full Text Available The biology and function of NKG2H receptor, unlike the better characterized members of the NKG2 family NKG2A, NKG2C, and NKG2D, remains largely unclear. Here, we show that NKG2H is able to associate with the signaling adapter molecules DAP12 and DAP10 suggesting that this receptor can signal for cell activation. Using a recently described NKG2H-specific monoclonal antibody (mAb, we have characterized the expression and function of lymphocytes that express this receptor. NKG2H is expressed at the cell surface of a small percentage of peripheral blood mononuclear cell (PBMC and is found more frequently on T cells, rather than NK cells. Moreover, although NKG2H is likely to trigger activation, co-cross-linking of this receptor with an NKG2H-specific mAb led to decreased T cell activation and proliferation in polyclonal PBMC cultures stimulated by anti-CD3 mAbs. This negative regulatory activity was seen only after cross-linking with NKG2H, but not NKG2A- or NKG2C-specific monoclonal antibodies. The mechanism underlying this negative effect is as yet unclear, but did not depend on the release of soluble factors or recognition of MHC class I molecules. These observations raise the intriguing possibility that NKG2H may be a novel marker for T cells able to negatively regulate T cell responses.

Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression

Science.gov (United States)

Makino, Yuichi; Cao, Renhai; Svensson, Kristian; Bertilsson, Göran; Asman, Mikael; Tanaka, Hirotoshi; Cao, Yihai; Berkenstam, Anders; Poellinger, Lorenz

2001-11-01

Alteration of gene expression is a crucial component of adaptive responses to hypoxia. These responses are mediated by hypoxia-inducible transcription factors (HIFs). Here we describe an inhibitory PAS (Per/Arnt/Sim) domain protein, IPAS, which is a basic helix-loop-helix (bHLH)/PAS protein structurally related to HIFs. IPAS contains no endogenous transactivation function but demonstrates dominant negative regulation of HIF-mediated control of gene expression. Ectopic expression of IPAS in hepatoma cells selectively impairs induction of genes involved in adaptation to a hypoxic environment, notably the vascular endothelial growth factor (VEGF) gene, and results in retarded tumour growth and tumour vascular density in vivo. In mice, IPAS was predominantly expressed in Purkinje cells of the cerebellum and in corneal epithelium of the eye. Expression of IPAS in the cornea correlates with low levels of expression of the VEGF gene under hypoxic conditions. Application of an IPAS antisense oligonucleotide to the mouse cornea induced angiogenesis under normal oxygen conditions, and demonstrated hypoxia-dependent induction of VEGF gene expression in hypoxic corneal cells. These results indicate a previously unknown mechanism for negative regulation of angiogenesis and maintenance of an avascular phenotype.

Nfatc2 and Tob1 have non-overlapping function in T cell negative regulation and tumorigenesis.

Directory of Open Access Journals (Sweden)

Sarah L May

Full Text Available Nfatc2 and Tob1 are intrinsic negative regulators of T cell activation. Nfatc2-deficient and Tob1-deficient T cells show reduced thresholds of activation; however, whether these factors have independent or overlapping roles in negative regulation of T cell responses has not been previously examined. Here, we show that Nfatc2 knockout (KO but not Tob1 KO mice have age-associated accumulation of persistently activated T cells in vivo and expansion of the CD44+ memory cell compartment and age-associated lymphocytic infiltrates in visceral organs, without significant changes in numbers of CD4+CD25+Foxp3+ regulatory T cells (Treg. In vitro, CD4+CD25- "conventional" T cells (Tconvs from both KO strains showed greater proliferation than wild type (WT Tconvs. However, while Tregs from Nfatc2 KO mice retained normal suppressive function, Tregs from Tob1 KOs had enhanced suppressive activity. Nfatc2 KO Tconvs expanded somewhat more rapidly than WT Tconvs under conditions of homeostatic proliferation, but their accelerated growth capacity was negated, at least acutely, in a lymphoreplete environment. Finally, Nfatc2 KO mice developed a previously uncharacterized increase in B-cell malignancies, which was not accelerated by the absence of Tob1. The data thus support the prevailing hypothesis that Nfatc2 and Tob1 are non-redundant regulators of lymphocyte homeostasis.

Integrating and differentiating aspects of self-regulation: effortful control, executive functioning, and links to negative affectivity.

Science.gov (United States)

Bridgett, David J; Oddi, Kate B; Laake, Lauren M; Murdock, Kyle W; Bachmann, Melissa N

2013-02-01

Subdisciplines within psychology frequently examine self-regulation from different frameworks despite conceptually similar definitions of constructs. In the current study, similarities and differences between effortful control, based on the psychobiological model of temperament (Rothbart, Derryberry, & Posner, 1994), and executive functioning are examined and empirically tested in three studies (n = 509). Structural equation modeling indicated that effortful control and executive functioning are strongly associated and overlapping constructs (Study 1). Additionally, results indicated that effortful control is related to the executive function of updating/monitoring information in working memory, but not inhibition (Studies 2 and 3). Study 3 also demonstrates that better updating/monitoring information in working memory and better effortful control were uniquely linked to lower dispositional negative affect, whereas the executive function of low/poor inhibition was uniquely associated with an increased tendency to express negative affect. Furthermore, dispositional negative affect mediated the links between effortful control and, separately, the executive function of updating/monitoring information in working memory and the tendency to express negative affect. The theoretical implications of these findings are discussed, and a potential framework for guiding future work directed at integrating and differentiating aspects of self-regulation is suggested. PsycINFO Database Record (c) 2013 APA, all rights reserved.

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

Science.gov (United States)

Kim, Yoon; Song, Ji-Hye; Park, Seon-U; Jeong, You-Seung; Kim, Soo-Hwan

2017-02-01

Brassinosteroids (BRs) are plant polyhydroxy-steroids that play important roles in plant growth and development via extensive signal integration through direct interactions between regulatory components of different signaling pathways. Recent studies have shown that diverse helix-loop-helix/basic helix-loop-helix (HLH/bHLH) family proteins are actively involved in control of BR signaling pathways and interact with other signaling pathways. In this study, we show that ATBS1-INTERACTING FACTOR 2 (AIF2), a nuclear-localized atypical bHLH transcription factor, specifically interacts with BRASSINOSTEROID-INSENSITIVE 2 (BIN2) among other BR signaling molecules. Overexpression of AIF2 down-regulated transcript expression of growth-promoting genes, thus resulting in retardation of growth. AIF2 renders plants hyposensitive to BR-induced root growth inhibition, but shows little effects on BR-promoted hypocotyl elongation. Notably, AIF2 was dephosphorylated by BR, and the dephosphorylated AIF2 was subject to proteasome-mediated degradation. AIF2 degradation was greatly induced by BR and ABA, but relatively slightly by other hormones such as auxin, gibberellin, cytokinin and ethylene. Moreover, AIF2 transcription was significantly suppressed by a BRI1/BZR1-mediated BR signaling pathway through a direct binding of BRASSINAZOLE RESISTANT 1 (BZR1) to the BR response element (BRRE) region of the AIF2 promoter. In conclusion, our study suggests that BIN2-driven AIF2 phosphorylation could augment the BIN2/AIF2-mediated negative circuit of BR signaling pathways, and the BR-induced transcriptional repression and protein degradation negatively regulate AIF2 transcription factor, reinforcing the BZR1/BES1-mediated positive BR signaling pathway. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Peer acceptance protects global self-esteem from negative effects of low closeness to parents during adolescence and early adulthood.

Science.gov (United States)

Birkeland, Marianne Skogbrott; Breivik, Kyrre; Wold, Bente

2014-01-01

Having a distant relationship with parents seems to increase the risk of developing a more negative global self-esteem. This article describes a longitudinal study of 1,090 Norwegian adolescents from the age of 13-23 (54 % males) that explored whether peer acceptance can act as a moderator and protect global self-esteem against the negative effects of experiencing low closeness in relationships with parents. A quadratic latent growth curve for global self-esteem with closeness to parents and peer acceptance as time-varying covariates was modeled, taking partial measurement invariance in global self-esteem into account. Peer acceptance was found to have a general protective effect on global self-esteem for all adolescents. In addition, at most ages, peer acceptance was found to have a protective-stabilizing effect on the relationship between closeness to parents and global self-esteem. This indicates that peer acceptance can be an especially valuable source of global self-esteem when closeness to parents is low.

Role of NeuroD1 on the negative regulation of Pomc expression by glucocorticoid.

Directory of Open Access Journals (Sweden)

Rehana Parvin

Full Text Available The mechanism of the negative regulation of proopiomelanocortin gene (Pomc by glucocorticoids (Gcs is still unclear in many points. Here, we demonstrated the involvement of neurogenic differentiation factor 1 (NeuroD1 in the Gc-mediated negative regulation of Pomc. Murine pituitary adrenocorticotropic hormone (ACTH producing corticotroph tumor-derived AtT20 cells were treated with dexamethasone (DEX (1-100 nM and cultured for 24 hrs. Thereafter, Pomc mRNA expression was studied by quantitative real-time PCR and rat Pomc promoter (-703/+58 activity was examined by luciferase assay. Both Pomc mRNA expression and Pomc promoter activity were inhibited by DEX in a dose-dependent manner. Deletion and point mutant analyses of Pomc promoter suggested that the DEX-mediated transcriptional repression was mediated via E-box that exists at -376/-371 in the promoter. Since NeuroD1 is known to bind to and activate E-box of the Pomc promoter, we next examined the effect of DEX on NeuroD1 expression. Interestingly, DEX dose-dependently inhibited NeuroD1 mRNA expression, mouse NeuroD1 promoter (-2.2-kb activity, and NeuroD1 protein expression in AtT20 cells. In addition, we confirmed the inhibitory effect of DEX on the interaction of NeuroD1 and E-box on Pomc promoter by chromatin immunoprecipitation (ChIP assay. Finally, overexpression of mouse NeuroD1 could rescue the DEX-mediated inhibition of Pomc mRNA expression and Pomc promoter activity. Taken together, it is suggested that the suppression of NeuroD1 expression and the inhibition of NeuroD1/E-box interaction may play an important role in the Gc-mediated negative regulation of Pomc.

Chondroitin-4-sulfation negatively regulates axonal guidance and growth

Science.gov (United States)

Wang, Hang; Katagiri, Yasuhiro; McCann, Thomas E.; Unsworth, Edward; Goldsmith, Paul; Yu, Zu-Xi; Tan, Fei; Santiago, Lizzie; Mills, Edward M.; Wang, Yu; Symes, Aviva J.; Geller, Herbert M.

2008-01-01

Summary Glycosaminoglycan (GAG) side chains endow extracellular matrix proteoglycans with diversity and complexity based upon the length, composition, and charge distribution of the polysaccharide chain. Using cultured primary neurons, we show that specific sulfation in the GAG chains of chondroitin sulfate (CS) mediates neuronal guidance cues and axonal growth inhibition. Chondroitin-4-sulfate (CS-A), but not chondroitin-6-sulfate (CS-C), exhibits a strong negative guidance cue to mouse cerebellar granule neurons. Enzymatic and gene-based manipulations of 4-sulfation in the GAG side chains alter their ability to direct growing axons. Furthermore, 4-sulfated CS GAG chains are rapidly and significantly increased in regions that do not support axonal regeneration proximal to spinal cord lesions in mice. Thus, our findings provide the evidence showing that specific sulfation along the carbohydrate backbone carries instructions to regulate neuronal function. PMID:18768934

An overview of practice and regulations concerning aircraft noise protection in Serbia

Directory of Open Access Journals (Sweden)

Mirković Bojana D.

2015-01-01

Full Text Available This paper gives an overview of studies and regulation concerning the issue of aircraft noise protection in Republic of Serbia. After crossing the limit of 50.000 operations in 2014, Airport 'Nikola Tesla' is classified as major airport, and with that urged to fulfill various requirements related to nose protection. Major airports are obliged to monitor noise, as well as to prepare strategic noise maps and action plans aiming to decrease number of people exposed to aircraft noise above acceptable level.

Zebrafish foxo3b negatively regulates canonical Wnt signaling to affect early embryogenesis.

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Xun-wei Xie

Full Text Available FOXO genes are involved in many aspects of development and vascular homeostasis by regulating cell apoptosis, proliferation, and the control of oxidative stress. In addition, FOXO genes have been showed to inhibit Wnt/β-catenin signaling by competing with T cell factor to bind to β-catenin. However, how important of this inhibition in vivo, particularly in embryogenesis is still unknown. To demonstrate the roles of FOXO genes in embryogenesis will help us to further understand their relevant physiological functions. Zebrafish foxo3b gene, an orthologue of mammalian FOXO3, was expressed maternally and distributed ubiquitously during early embryogenesis and later restricted to brain. After morpholino-mediated knockdown of foxo3b, the zebrafish embryos exhibited defects in axis and neuroectoderm formation, suggesting its critical role in early embryogenesis. The embryo-developmental marker gene staining at different stages, phenotype analysis and rescue assays revealed that foxo3b acted its role through negatively regulating both maternal and zygotic Wnt/β-catenin signaling. Moreover, we found that foxo3b could interact with zebrafish β-catenin1 and β-catenin2 to suppress their transactivation in vitro and in vivo, further confirming its role relevant to the inhibition of Wnt/β-catenin signaling. Taken together, we revealed that foxo3b played a very important role in embryogenesis and negatively regulated maternal and zygotic Wnt/β-catenin signaling by directly interacting with both β-catenin1 and β-catenin2. Our studies provide an in vivo model for illustrating function of FOXO transcription factors in embryogenesis.

Establishment and maintenance of regulating ecosystem services in a dryland area of Central Asia: the Kökyar Protection Forest, Aksu, NW China, as an example

Science.gov (United States)

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.

WRKY54 and WRKY70 co-operate as negative regulators of leaf senescence in Arabidopsis thaliana

OpenAIRE

Besseau, Sébastien; Li, Jing; Palva, E. Tapio

2012-01-01

The plant-specific WRKY transcription factor (TF) family with 74 members in Arabidopsis thaliana appears to be involved in the regulation of various physiological processes including plant defence and senescence. WRKY53 and WRKY70 were previously implicated as positive and negative regulators of senescence, respectively. Here the putative function of other WRKY group III proteins in Arabidopsis leaf senescence has been explored and the results suggest the involvement of two additional WRKY TF...

The negative cell cycle regulator, Tob (transducer of ErbB-2), is involved in motor skill learning

International Nuclear Information System (INIS)

Wang Xinming; Gao Xiang; Zhang Xuehan; Tu Yanyang; Jin Meilei; Zhao Guoping; Yu Lei; Jing Naihe; Li Baoming

2006-01-01

Tob (transducer of ErbB-2) is a negative cell cycle regulator with anti-proliferative activity in peripheral tissues. Our previous study identified Tob as a protein involved in hippocampus-dependent memory consolidation (M.L. Jin, X.M. Wang, Y.Y. Tu, X.H. Zhang, X. Gao, N. Guo, Z.Q. Xie, G.P. Zhao, N.H. Jing, B.M. Li, Y.Yu, The negative cell cycle regulator, Tob (Transducer of ErbB-2), is a multifunctional protein involved in hippocampus-dependent learning and memory, Neuroscience 131 (2005) 647-659). Here, we provide evidence that Tob in the central nervous system is engaged in acquisition of motor skill. Tob has a relatively high expression in the cerebellum. Tob expression is up-regulated in the cerebellum after rats receive training on a rotarod-running task. Rats infused with Tob antisense oligonucleotides into the 4th ventricle exhibit a severe deficit in running on a rotating rod or walking across a horizontally elevated beam

[Plant protection products and their residues : Aspects of consumer safety in context of the new EU regulations].

Science.gov (United States)

Banasiak, U; Michalski, B; Pfeil, R; Solecki, R

2010-06-01

The law regulating plant protection products (PPP) in the European Union (EU) was fundamentally revised through the introduction of Regulation (EC) No. 1107/2009 which is due to enter into force on 14 June 2011. EU-wide harmonized maximum residue levels (MRLs) for the active substances of PPP in foods are laid down in Regulation (EC) No. 396/2005 and apply since entry into force of the regulation on 1 September 2008. The goal of both regulations is to strengthen the level of consumer protection. PPP are subject to a strict assessment of active substances, which is regulated at the EU level as well as an authorization procedure in the EU Member States. Prior to application for authorization of a PPP, the active substance(s) it contains must be included in a positive list. Tests regarding the toxicity and residue behavior of PPP must be conducted by the applicant, and the respective documents must be submitted to the authorities for evaluation. Following review of the required data, toxicological threshold values are derived, consumer exposure is assessed, and the risk to health is evaluated. The goal of this evaluation is to ensure that the use of PPP according to good plant protection practice does not have any harmful effects on human health.

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

Science.gov (United States)

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

2014-07-01

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

SALT-RESPONSIVE ERF1 is a negative regulator of grain filling and gibberellin-mediated seedling establishment in rice.

Science.gov (United States)

Schmidt, Romy; Schippers, Jos H M; Mieulet, Delphine; Watanabe, Mutsumi; Hoefgen, Rainer; Guiderdoni, Emmanuel; Mueller-Roeber, Bernd

2014-02-01

Grain quality is an important agricultural trait that is mainly determined by grain size and composition. Here, we characterize the role of the rice transcription factor (TF) SALT-RESPONSIVE ERF1 (SERF1) during grain development. Through genome-wide expression profiling and chromatin immunoprecipitation, we found that SERF1 directly regulates RICE PROLAMIN-BOX BINDING FACTOR (RPBF), a TF that functions as a positive regulator of grain filling. Loss of SERF1 enhances RPBF expression resulting in larger grains with increased starch content, while SERF1 overexpression represses RPBF resulting in smaller grains. Consistently, during grain filling, starch biosynthesis genes such as GRANULE-BOUND STARCH SYNTHASEI (GBSSI), STARCH SYNTHASEI (SSI), SSIIIa, and ADP-GLUCOSE PYROPHOSPHORYLASE LARGE SUBUNIT2 (AGPL2) are up-regulated in SERF1 knockout grains. Moreover, SERF1 is a direct upstream regulator of GBSSI. In addition, SERF1 negatively regulates germination by controlling RPBF expression, which mediates the gibberellic acid (GA)-induced expression of RICE AMYLASE1A (RAmy1A). Loss of SERF1 results in more rapid seedling establishment, while SERF1 overexpression has the opposite effect. Our study reveals that SERF1 represents a negative regulator of grain filling and seedling establishment by timing the expression of RPBF.

Radiation protection - Revision of French radiation protection regulations (1988)

International Nuclear Information System (INIS)

Mayoux, J.C.

1989-01-01

This article analyses the recent amendments to the 1966 and 1975 Decrees on general radiation protection principles and radiation protection of workers in large nuclear installations respectively and also describes national radiation protection law. In particular, the amendments incorporate the revised EURATOM basic radiation protection standards and the new international units (sievert and becquerel replace rem and curie) in the Decrees. (NEA) [fr

MicroRNA, miR-374b, directly targets Myf6 and negatively regulates C2C12 myoblasts differentiation

Energy Technology Data Exchange (ETDEWEB)

Ma, Zhiyuan; Sun, Xiaorui; Xu, Dequan; Xiong, Yuanzhu; Zuo, Bo, E-mail: zuobo@mail.hzau.edu.cn

2015-11-27

Myogenesis is a complex process including myoblast proliferation, differentiation and myotube formation and is controlled by myogenic regulatory factors (MRFs), MyoD, MyoG, Myf5 and Myf6 (also known as MRF4). MicroRNA is a kind of ∼22 nt-long non-coding small RNAs, and act as key transcriptional or post-transcriptional regulators of gene expression. Identification of miRNAs involved in the regulation of muscle genes could improve our understanding of myogenesis process. In this study, we investigated the regulation of Myf6 gene by miRNAs. We showed that miR-374b specifically bound to the 3'untranslated region (UTR) of Myf6 and down-regulated the expression of Myf6 gene at both mRNA and protein level. Furthermore, miR-374b is ubiquitously expressed in the tissues of adult C57BL6 mouse, and the mRNA abundance increases first and then decreases during C2C12 myoblasts differentiation. Over-expression of miR-374b impaired C2C12 cell differentiation, while inhibiting miR-374b expression by 2′-O-methyl antisense oligonucleotides promoted C2C12 cell differentiation. Taken together, our findings identified miR-374b directly targets Myf6 and negatively regulates myogenesis. - Highlights: • MiR-374b directly targets 3′UTR of Myf6. • MiR-374b negatively regulates Myf6 in C2C12 cells. • MiR-374b abundance significiently changes during C2C12 cells differentiation. • MiR-374b negatively regulates C2C12 cells differentiation.

The system of radiation protection: views from the Australian regulator (Arpansa)

International Nuclear Information System (INIS)

Prosser, S.

2004-01-01

Of those issues identified by the EGRP at previous meetings, there are a number of areas where, from the Australian perspective, the current system of radiological protection could benefit from change. These include stakeholder issues, the environment, inconsistencies in numerical values and risk comparison with more common hazards. Implementing any recommended changes would present some bureaucratic challenges but would also provide an opportunity for increasing national uniformity of regulation. However it is recognised that the current system does not provide an unacceptable level of protection and it is therefore important that any proposed changes are thoroughly tested in practice to ensure a real net benefit. (author)

Co-regulation in EU personal data protection : The case of technical standards and the privacy by design standardisation ‘mandate’

NARCIS (Netherlands)

Kamara, Irene

The recently adopted General Data Protection Regulation (GDPR), a technology-neutral law, endorses self-regulatory instruments, such as certification and technical standards. Even before the adoption of the General Data Protection Regulation, standardisation activity in the field of privacy

EGR-1 and DUSP-1 are important negative regulators of pro-allergic responses in airway epithelium

NARCIS (Netherlands)

Golebski, Korneliusz; van Egmond, Danielle; de Groot, Esther J.; Roschmann, Kristina I. L.; Fokkens, Wytske J.; van Drunen, Cornelis M.

2015-01-01

Background: Primary nasal epithelium of house dust mite allergic individuals is in a permanently activated inflammatory transcriptional state. Objective: To investigate whether a deregulated expression of EGR-1 and/or DUSP-1, two potential negative regulators of pro-inflammatory responses, could

BRAFV600E Negatively Regulates the AKT Pathway in Melanoma Cell Lines

OpenAIRE

Chen, Brenden; Tardell, Christine; Higgins, Brian; Packman, Kathryn; Boylan, John F.; Niu, Huifeng

2012-01-01

Cross-feedback activation of MAPK and AKT pathways is implicated as a resistance mechanism for cancer therapeutic agents targeting either RAF/MEK or PI3K/AKT/mTOR. It is thus important to have a better understanding of the molecular resistance mechanisms to improve patient survival benefit from these agents. Here we show that BRAFV600E is a negative regulator of the AKT pathway. Expression of BRAFV600E in NIH3T3 cells significantly suppresses MEK inhibitor (RG7167) or mTORC1 inhibitor (rapamy...

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

Directory of Open Access Journals (Sweden)

Jianjin Guo

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

Adaptive disengagement buffers self-esteem from negative social feedback.

Science.gov (United States)

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

2014-11-01

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

Review of the general regulation of radiological protection

International Nuclear Information System (INIS)

Cortes C, A.

2008-12-01

As a result of advances in radiation protection at the international level, the National Commission of Nuclear Safety and Safeguards has been given the task of revising the General Regulation of Radiation Safety to cover such developments, especially those contained in the safety basic standards No. 115 of the IAEA, published in 1977. In addition, the working group has considered issues that need to be regulated to avoid unnecessary dose received by the public due to exposure to ionizing radiation. Related to the public exposure believes the preliminary deal with situations of chronic exposure in homes, as well as human activities involving natural sources of ionizing radiation exposure to cause the public to levels that exceed the dose limits laid down in the Regulation. It is also envisaged that they will be subject to monitoring by the Commission, the concentration levels due to radon in homes, radon outdoor, radio and radon in drinking water, and external radiation levels due to naturally occurring radionuclides in building materials. Thus, the processes that may be subject to surveillance by the National Commission of Nuclear Safety and Safeguards include water treatment, some metallurgical processes, some of the mining industry and some industrial processes in which waste increase activity concentration of naturally occurring radionuclides. With the revision of the General Regulation of Radiation Safety, certain standards must be reviewed and further developed such as the concentration of radon levels in homes room, outdoor radon, radon and radio in drinking water, radiation levels out sourcing due to naturally occurring radionuclides in building materials, and standards governing (and identify) the radioactive material generation in the processes mentioned previously. (Author)

Effect of Negative Pressure on Proliferation, Virulence Factor Secretion, Biofilm Formation, and Virulence-Regulated Gene Expression of Pseudomonas aeruginosa In Vitro

Directory of Open Access Journals (Sweden)

Guo-Qi Wang

2016-01-01

Full Text Available Objective. To investigate the effect of negative pressure conditions induced by NPWT on P. aeruginosa. Methods. P. aeruginosa was cultured in a Luria–Bertani medium at negative pressure of −125 mmHg for 24 h in the experimental group and at atmospheric pressure in the control group. The diameters of the colonies of P. aeruginosa were measured after 24 h. ELISA kit, orcinol method, and elastin-Congo red assay were used to quantify the virulence factors. Biofilm formation was observed by staining with Alexa Fluor® 647 conjugate of concanavalin A (Con A. Virulence-regulated genes were determined by quantitative RT-PCR. Results. As compared with the control group, growth of P. aeruginosa was inhibited by negative pressure. The colony size under negative pressure was significantly smaller in the experimental group than that in the controls (p<0.01. Besides, reductions in the total amount of virulence factors were observed in the negative pressure group, including exotoxin A, rhamnolipid, and elastase. RT-PCR results revealed a significant inhibition in the expression level of virulence-regulated genes. Conclusion. Negative pressure could significantly inhibit the growth of P. aeruginosa. It led to a decrease in the virulence factor secretion, biofilm formation, and a reduction in the expression level of virulence-regulated genes.

[Croatian and international regulations on the protection and rights of workers exposed to asbestos at work].

Science.gov (United States)

Zavalić, Marija; Macan, Jelena

2009-11-01

New regulations on the protection and rights of workers occupationally exposed to asbestos were introduced in Croatia in 2007 and 2008. They have been harmonised with the European Union (EU) and International Labour Organization (ILO) regulations, and make a step forward in safety at work, health protection, social rights, and pension schemes for Croatian workers occupationally exposed to asbestos. The 2007 Croatian regulation on the protection of workers from the risks related to exposure to asbestos at work defines and describes activities in which workers can be occupationally exposed to asbestos, defines the threshold value of asbestos in the air at work, defines valid methods for measurement of asbestos concentrations in the air, and establishes measures to reduce asbestos exposure at work or protect the exposed workers. Croatian law regulating obligatory health surveillance of workers occupationally exposed to asbestos from year 2007 defines activities and competent authorities to implement health surveillance of workers occupationally exposed to asbestos and to diagnose occupational diseases related to asbestos. This law also defines "occupational exposure to asbestos", and "occupational asbestos-related diseases", including asbestosis (pulmonary asbestos-related fibrosis), pleural asbestos-related disorders (plaques, pleural thickening, and benign effusion), lung and bronchial cancer, and malignant mesothelioma of serous membranes. These regulations have been harmonised with ILO, Directive 2003/18/EC amending Council Directive 83/477/EEC on the protection of workers from the risks related to exposure to asbestos at work, and with the Commission Recommendation 2003/670/EC concerning the European schedule of occupational diseases. The 2008 Croatian regulation on conditions of health surveillance, diagnostic procedures and criteria for confirmation of occupational asbestos-related diseases "defines the terms and the content of medical examination of workers

Legal regulation of the protection of animals in human care

OpenAIRE

Kubánková, Lenka

2014-01-01

This diploma thesis summarizes regulation of animal in human care protection. It describes international conventions and also European Union and Czech laws. It includes definition of animal and categorizations of animals. The status of animal in Czech civil law is content of this thesis too. On international level are the most important conventions of Council of Europe. The part of this work concerning European Union includes conceptual tools, primary law and secondary law. The main law in Cz...

delta-EF1 is a negative regulator of Ihh in the developing growth plate.

Science.gov (United States)

Bellon, Ellen; Luyten, Frank P; Tylzanowski, Przemko

2009-11-30

Indian hedgehog (Ihh) regulates proliferation and differentiation of chondrocytes in the growth plate. Although the biology of Ihh is currently well documented, its transcriptional regulation is poorly understood. delta-EF1 is a two-handed zinc finger/homeodomain transcriptional repressor. Targeted inactivation of mouse delta-EF1 leads to skeletal abnormalities including disorganized growth plates, shortening of long bones, and joint fusions, which are reminiscent of defects associated with deregulation of Ihh signaling. Here, we show that the absence of delta-EF1 results in delayed hypertrophic differentiation of chondrocytes and increased cell proliferation in the growth plate. Further, we demonstrate that delta-EF1 binds to the putative regulatory elements in intron 1 of Ihh in vitro and in vivo, resulting in down-regulation of Ihh expression. Finally, we show that delta-EF1 haploinsufficiency leads to a postnatal increase in trabecular bone mass associated with enhanced Ihh expression. In summary, we have identified delta-EF1 as an in vivo negative regulator of Ihh expression in the growth plate.

Power supply system for negative ion source at IPR

Science.gov (United States)

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

Power supply system for negative ion source at IPR

International Nuclear Information System (INIS)

Gahlaut, Agrajit; Sonara, Jashwant; Parmar, K G; Soni, Jignesh; Bandyopadhyay, M; Singh, Mahendrajit; Bansal, Gourab; Pandya, Kaushal; Chakraborty, Arun

2010-01-01

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 x 10 12 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

Anxiety symptoms mediate the relationship between exposure to stressful negative life events and depressive symptoms: A conditional process modelling of the protective effects of resilience.

Science.gov (United States)

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.

Interpretations and Implementation of the Regulations on the Protection of Danube Delta Biosphere Reserve

Directory of Open Access Journals (Sweden)

Dorin Matei

2015-08-01

Full Text Available The Danube Delta Biosphere Reserve, part of the UNESCO world patrimony since 1992, enjoys an enhanced legislative protection regarding the protection of fauna and flora. In Romania we find the legislation in the field of traffic regulations on ships and boats on the Danube, on canals and inland lakes in the Danube Delta area, and in fisheries and protection of animals and plants. The state of the environment in the Danube Delta Biosphere Reserve is constantly analyzed, achieving annual public reports. The aim of the paper is the interpretation of legal provisions both in the field, making proposals de lege ferenda for the smooth running of traffic and environmental protection in the Delta.

Critical role of types 2 and 3 deiodinases in the negative regulation of gene expression by T₃in the mouse cerebral cortex.

Science.gov (United States)

Hernandez, Arturo; Morte, Beatriz; Belinchón, Mónica M; Ceballos, Ainhoa; Bernal, Juan

2012-06-01

Thyroid hormones regulate brain development and function through the control of gene expression, mediated by binding of T(3) to nuclear receptors. Brain T(3) concentration is tightly controlled by homeostatic mechanisms regulating transport and metabolism of T(4) and T(3). We have examined the role of the inactivating enzyme type 3 deiodinase (D3) in the regulation of 43 thyroid hormone-dependent genes in the cerebral cortex of 30-d-old mice. D3 inactivation increased slightly the expression of two of 22 positively regulated genes and significantly decreased the expression of seven of 21 negatively regulated genes. Administration of high doses of T(3) led to significant changes in the expression of 12 positive genes and three negative genes in wild-type mice. The response to T(3) treatment was enhanced in D3-deficient mice, both in the number of genes and in the amplitude of the response, demonstrating the role of D3 in modulating T(3) action. Comparison of the effects on gene expression observed in D3 deficiency with those in hypothyroidism, hyperthyroidism, and type 2 deiodinase (D2) deficiency revealed that the negative genes are more sensitive to D2 and D3 deficiencies than the positive genes. This observation indicates that, in normal physiological conditions, D2 and D3 play critical roles in maintaining local T(3) concentrations within a very narrow range. It also suggests that negatively and positively regulated genes do not have the same physiological significance or that their regulation by thyroid hormone obeys different paradigms at the molecular or cellular levels.

MYB52 Negatively Regulates Pectin Demethylesterification in Seed Coat Mucilage.

Science.gov (United States)

Shi, Dachuan; Ren, Angyan; Tang, Xianfeng; Qi, Guang; Xu, Zongchang; Chai, Guohua; Hu, Ruibo; Zhou, Gongke; Kong, Yingzhen

2018-04-01

Pectin, which is a major component of the plant primary cell walls, is synthesized and methyl-esterified in the Golgi apparatus and then demethylesterified by pectin methylesterases (PMEs) located in the cell wall. The degree of methylesterification affects the functional properties of pectin, and thereby influences plant growth, development and defense. However, little is known about the mechanisms that regulate pectin demethylesterification. Here, we show that in Arabidopsis ( Arabidopsis thaliana ) seed coat mucilage, the absence of the MYB52 transcription factor is correlated with an increase in PME activity and a decrease in the degree of pectin methylesterification. Decreased methylesterification in the myb52 mutant is also correlated with an increase in the calcium content of the seed mucilage. Chromatin immunoprecipitation analysis and molecular genetic studies suggest that MYB52 transcriptionally activates PECTIN METHYLESTERASE INHIBITOR6 ( PMEI6 ), PMEI14 , and SUBTILISIN-LIKE SER PROTEASE1.7 ( SBT1.7 ) by binding to their promoters. PMEI6 and SBT1.7 have previously been shown to be involved in seed coat mucilage demethylesterification. Our characterization of two PMEI14 mutants suggests that PMEI14 has a role in seed coat mucilage demethylesterification, although its activity may be confined to the seed coat in contrast to PMEI6, which functions in the whole seed. Our demonstration that MYB52 negatively regulates pectin demethylesterification in seed coat mucilage, and the identification of components of the molecular network involved, provides new insight into the regulatory mechanism controlling pectin demethylesterification and increases our understanding of the transcriptional regulation network involved in seed coat mucilage formation. © 2018 American Society of Plant Biologists. All Rights Reserved.

Consolidated permit regulations and hazardous waste management system: Environmental Protection Agency. Notice of issuance of regulation interpretation memorandum.

Science.gov (United States)

1981-12-10

The Environmental Protection Agency (EPA) is issuing today a Regulation Interpretation Memorandum (RIM) which provides official interpretation of the issue of whether a generator who accumulates hazardous waste pursuant to 40 CFR 262.34, may qualify for interim status after November 19, 1980. This issue arose when the requirements for submitting a Part A permit application (one of the prerequisites to qualifying for interim status) were amended on November 19, 1980. The provisions interpreted today are part of the Consolidated Permit Regulations promulgated under Subtitle C of the Solid Waste Disposal Act, as amended by the Resource Conservation and Recovery Act, as amended (RCRA).

Comparison between the Brazilian regulation of radioprotection and the recommendation of International Commission on Radiological Protection published in 2007

International Nuclear Information System (INIS)

Pereira, Wagner S.; Py Junior, Delcy A.; Dantas, Marcelino V.A.; Oliveira, Sergio Q. de; Kelecom, Alphonse; Mortagua, Valter Jose

2011-01-01

This paper intends to compare the Brasilian basic regulation on radiological protection with the new recommendations of ICRP through existent differences. The main difference between the publication 60 and the publication 103 of the ICRP is the changing of concept of protection based on the process by use of practice and intervention concepts, to the protection based on the exposure situation, through the concepts of planned exposure, emergency and existent situation. For adequacy to the Brazilian regulation it is necessary to change its concept of protection and the values of radiation weighing and tissues, up dating of radiation detriments, besides to make clear the concept of environmental radioprotection

[Radiation protection in orthopaedics: implications for clinical practice of the new regulations governing roentgen ray irradiation and radioprotection].

Science.gov (United States)

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.

Mechanisms of JAK/STAT pathway negative regulation by the short coreceptor Eye Transformer/Latran.

Science.gov (United States)

Fisher, Katherine H; Stec, Wojciech; Brown, Stephen; Zeidler, Martin P

2016-02-01

Transmembrane receptors interact with extracellular ligands to transduce intracellular signaling cascades, modulate target gene expression, and regulate processes such as proliferation, apoptosis, differentiation, and homeostasis. As a consequence, aberrant signaling events often underlie human disease. Whereas the vertebrate JAK/STAT signaling cascade is transduced via multiple receptor combinations, the Drosophila pathway has only one full-length signaling receptor, Domeless (Dome), and a single negatively acting receptor, Eye Transformer/Latran (Et/Lat). Here we investigate the molecular mechanisms underlying Et/Lat activity. We demonstrate that Et/Lat negatively regulates the JAK/STAT pathway activity and can bind to Dome, thus reducing Dome:Dome homodimerization by creating signaling-incompetent Dome:Et/Lat heterodimers. Surprisingly, we find that Et/Lat is able to bind to both JAK and STAT92E but, despite the presence of putative cytokine-binding motifs, does not detectably interact with pathway ligands. We find that Et/Lat is trafficked through the endocytic machinery for lysosomal degradation but at a much slower rate than Dome, a difference that may enhance its ability to sequester Dome into signaling-incompetent complexes. Our data offer new insights into the molecular mechanism and regulation of Et/Lat in Drosophila that may inform our understanding of how short receptors function in other organisms. © 2016 Fisher et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Endothelium derived nitric oxide synthase negatively regulates the PDGF-survivin pathway during flow-dependent vascular remodeling.

Directory of Open Access Journals (Sweden)

Jun Yu

Full Text Available Chronic alterations in blood flow initiate structural changes in vessel lumen caliber to normalize shear stress. The loss of endothelial derived nitric oxide synthase (eNOS in mice promotes abnormal flow dependent vascular remodeling, thus uncoupling mechanotransduction from adaptive vascular remodeling. However, the mechanisms of how the loss of eNOS promotes abnormal remodeling are not known. Here we show that abnormal flow-dependent remodeling in eNOS knockout mice (eNOS (-/- is associated with activation of the platelet derived growth factor (PDGF signaling pathway leading to the induction of the inhibitor of apoptosis, survivin. Interfering with PDGF signaling or survivin function corrects the abnormal remodeling seen in eNOS (-/- mice. Moreover, nitric oxide (NO negatively regulates PDGF driven survivin expression and cellular proliferation in cultured vascular smooth muscle cells. Collectively, our data suggests that eNOS negatively regulates the PDGF-survivin axis to maintain proportional flow-dependent luminal remodeling and vascular quiescence.

An assessment of the fire protection requirements throughout a NPP life related to current IAEA regulations and American, Canadian and UE regulations

International Nuclear Information System (INIS)

Branzeu, N.; Necula, D.; Badea, M.; Teodorescu, D.; Peteu, M.

2006-01-01

Statistics on fires has surprisingly shown that the frequency of fires in a nuclear power plant are as high as in the conventional industrial units. The analyses on fires occurred in a NPP need to consider both their well-known severe damages and the nuclear consequences. In 1975 a severe fire occurred in BROWNS FERRY NPP due to the ignition of the polyurethane foam used in the electric cable penetration sealings. The fire propagated to the cable channels and damaged over 1600 cables. The fire event revealed important shortcomings in the fire protection design and procedures. The fire represented a crucial event that changed fundamentally the fire protection regulation in the United States nuclear industry. The fire protection programs, standards and guides currently applied, have been developed on basis of this fire analysis and gained conclusions/experience. The purpose of the article is to be a short presentation of the fire protection requirements for all NPP life stages (i.e. design, construction, commissioning, operation and decommissioning), including the most recent issues of the standards, codes, guides and regulations in US, Canada, IAEA and some European countries. Such documentation represented the main technical support in establishing the national fire protection standard design regarding all the stages of a CANDU-6 NPP life, all the types of operational NPPs, particularly for Cernavoda NPP Unit 1 and Unit 2 (now in an advanced stage of construction). In order to satisfy the requirements provided by this documentation, as practically as possible, a list of analyses and fire protection improvement measures for Cernavoda NPP is presented. (authors)

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

Energy Technology Data Exchange (ETDEWEB)

Sung, Nak-Yun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Yang, Mi-So [Department of Microbiology, Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Song, Du-Sub [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); School of life sciences and Biotechnology, Korea University 5-ka, Anam-Dong, Sungbuk-ku, Seoul 136-701 (Korea, Republic of); Kim, Jae-Kyung; Park, Jong-Heum; Song, Beom-Seok; Park, Sang-Hyun; Lee, Ju-Woon [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Park, Hyun-Jin [School of life sciences and Biotechnology, Korea University 5-ka, Anam-Dong, Sungbuk-ku, Seoul 136-701 (Korea, Republic of); Kim, Jae-Hun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Byun, Eui-Baek, E-mail: ebbyun80@kaeri.re.kr [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Byun, Eui-Hong, E-mail: ehbyun80@kongju.ac.k [Department of Food Science and Technology, Kongju National University, Yesan 340-800 (Korea, Republic of)

2013-08-16

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

Osteoprotegerin CGA haplotype protection against cerebrovascular complications in anti-CCP negative patients with rheumatoid arthritis.

Directory of Open Access Journals (Sweden)

Fernanda Genre

Full Text Available Rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis.Three OPG gene variants (rs3134063, rs2073618 and rs3134069 were genotyped by TaqMan assays in 2027 Spanish patients with rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP antibody testing was positive in 997 of 1714 tested. Also, 18.3% of the whole series had experienced cardiovascular events, including 5.4% with cerebrovascular accidents. The relationship between OPG variants and cardiovascular events was assessed using Cox regression.No association between OPG gene variants and cardiovascular disease was observed in the whole group of rheumatoid arthritis patients or in anti-CCP positive patients. Nevertheless, a protective effect of CGA haplotype on the risk of cardiovascular disease in general, and specifically in the risk of cerebrovascular complications after adjusting for sex, age at disease diagnosis and traditional cardiovascular risk factors was disclosed in anti-CCP negative patients (HR = 0.54; 95%CI: 0.31-0.95; p = 0.032 and HR = 0.17; 95%CI: 0.04-0.78; p = 0.022, respectively.Our results indicate a protective effect of the OPG CGA haplotype on cardiovascular risk, mainly due to a protective effect against cerebrovascular events in anti-CCP negative rheumatoid arthritis patients.

Peer Acceptance Protects Global Self-esteem from Negative Effects of Low Closeness to Parents During Adolescence and Early Adulthood

OpenAIRE

Birkeland, Marianne Skogbrott; Breivik, Kyrre; Wold, Bente

2013-01-01

Having a distant relationship with parents seems to increase the risk of developing a more negative global self-esteem. This article describes a longitudinal study of 1,090 Norwegian adolescents from the age of 13–23 (54 % males) that explored whether peer acceptance can act as a moderator and protect global self-esteem against the negative effects of experiencing low closeness in relationships with parents. A quadratic latent growth curve for global self-esteem with closeness to parents and ...

Impact of general data protection regulation on children's rights in digital environment

Directory of Open Access Journals (Sweden)

Krivokapić Đorđe

2016-01-01

Full Text Available Raising the age of consent to data processing to 16 and allowing member states to set it at a lower age, was one of the major points of argument in the wake of passing the new EU General Data Protection Regulation (GDPR, otherwise hailed for introducing the Article 8 that recognizes children as a vulnerable group. This paper analyzes legal grounds for concerns raised over the provisions related to personal data protection of minors, possible ramifications and remedies within the given framework. It also highlights innovations and positive solutions set in the GDPR, with respect to privacy risks and opportunities for children in the information society.

Regulation and inspection support radiation protection in nuclear and other installations

International Nuclear Information System (INIS)

Williams, M.K.; Potter, C.; Harbison, S.A.

1996-01-01

Over the past fifty years, radiation protection legislation in the UK has developed from a narrow industry-specific base to a comprehensive package of regulations and supporting Approved Code of Practice, with additional provisions for nuclear installations. Development of this legislation mirrors progress in international understanding about the risks from exposure to ionising radiation. The current Ionising Radiations Regulations 1985 largely implement the Euratom 1980 Basic Safety Standards Directive and place particular emphasis on the need to keep exposure as low as reasonably practicable. The regulations have been underpinned by the development of the concept of the Tolerability of Risk and the application of the ALARP/ALARA principle, particularly at nuclear installations. Analysis of dose data on HSE's Central Index of Dose Information has shown the general success of this approach in the UK; the data have also allowed targeting of inspection effort. Currently, the Health and Safety Commission and Executive are developing plans for implementing the revised EU Basic Safety Standards Directive. (author)

Thyroid hormone negatively regulates CDX2 and SOAT2 mRNA expression via induction of miRNA-181d in hepatic cells

Energy Technology Data Exchange (ETDEWEB)

Yap, Chui Sun; Sinha, Rohit Anthony [Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, 8, College Road, Singapore 169857 (Singapore); Ota, Sho; Katsuki, Masahito [Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai 980-8575 (Japan); Yen, Paul Michael, E-mail: paul.yen@duke-nus.edu.sg [Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, 8, College Road, Singapore 169857 (Singapore)

2013-11-01

Highlights: •Thyroid hormone induces miR-181d expression in human hepatic cells and mouse livers. •Thyroid hormone downregulates CDX2 and SOAT2 (or ACAT2) via miR-181d. •miR-181d reduces cholesterol output from human hepatic cells. -- Abstract: Thyroid hormones (THs) regulate transcription of many metabolic genes in the liver through its nuclear receptors (TRs). Although the molecular mechanisms for positive regulation of hepatic genes by TH are well understood, much less is known about TH-mediated negative regulation. Recently, several nuclear hormone receptors were shown to downregulate gene expression via miRNAs. To further examine the potential role of miRNAs in TH-mediated negative regulation, we used a miRNA microarray to identify miRNAs that were directly regulated by TH in a human hepatic cell line. In our screen, we discovered that miRNA-181d is a novel hepatic miRNA that was regulated by TH in hepatic cell culture and in vivo. Furthermore, we identified and characterized two novel TH-regulated target genes that were downstream of miR-181d signaling: caudal type homeobox 2 (CDX2) and sterol O-acyltransferase 2 (SOAT2 or ACAT2). CDX2, a known positive regulator of hepatocyte differentiation, was regulated by miR-181d and directly activated SOAT2 gene expression. Since SOAT2 is an enzyme that generates cholesteryl esters that are packaged into lipoproteins, our results suggest miR-181d plays a significant role in the negative regulation of key metabolic genes by TH in the liver.

Sun protection provided by regulation school uniforms in Australian schools: an opportunity to improve personal sun protection during childhood.

Science.gov (United States)

Turner, Denise; Harrison, Simone L

2014-01-01

Childhood sun exposure is linked to excessive pigmented mole development and melanoma risk. Clothing provides a physical barrier, protecting skin from ultraviolet radiation (UVR). Extending sleeves to elbow length and shorts to knee length has been shown to significantly reduce mole acquisition in preschoolers from tropical Queensland. We used publicly available uniform images and guidelines from primary schools in Townsville (latitude 19.25°S, n = 43 schools), Cairns (16.87°S, n = 46) and the Atherton Tablelands (17.26°S, n = 23) in tropical Australia to objectively determine the body surface proportion covered by regulation school uniforms. Uniforms of nongovernment, large (≥800 students), urban, educationally advantaged schools with comprehensive sun protection policies covered more skin than those of government schools (63.2% vs 62.0%; P schools (63.4% vs 62.3%; P = 0.009), rural (62.7% vs 61.9%; P = 0.002) and educationally disadvantaged schools (62.8% vs 62.3%; P school uniforms covered identical body surface proportions (62.4%, P = 0.084). Although wearing regulation school uniforms is mandatory at most Australian primary schools, this opportunity to improve children's sun protection is largely overlooked. Recent evidence suggests that even encouraging minor alterations to school uniforms (e.g. slightly longer sleeves/dresses/skirts/shorts) to increase skin coverage may reduce mole acquisition and melanoma risk, especially in high-risk populations. © 2014 The American Society of Photobiology.

All-trans retinoic acid negatively regulates cytotoxic activities of nature killer cell line 92

International Nuclear Information System (INIS)

Li Ang; He Meilan; Wang Hui; Qiao Bin; Chen Ping; Gu Hua; Zhang Mengjie; He Shengxiang

2007-01-01

NK cells are key components of innate immune systems and their activities are regulated by cytokines and hormones. All-trans retinoic acid (ATRA), as a metabolite of vitamin A and an immunomodulatory hormone, plays an important role in regulating immune responses. In the present study, we investigated the effect of ATRA on human NK cell line NK92. We found that ATRA dose-dependently suppressed cytotoxic activities of NK92 cells without affecting their proliferation. To explore the mechanisms underlying the ATRA influence on NK92 cells, we examined the production of cytokines (TNF-α, IFN-γ), gene expression of cytotoxic-associated molecules (perforin, granzyme B, nature killer receptors (NCRs), and NKG2D), and the activation of NF-κB pathways related with immune response. Our results demonstrated that ATRA suppressed NF-κB activity and prevented IκBα degradation in a dose-dependent way, inhibited IFN-γ production and gene expression of granzyme B and NKp46. Our findings suggest that ATRA is a negative regulator of NK92 cell activation and may act as a potential regulator of anti-inflammatory functions in vivo

Early-Occurring Maternal Depression and Maternal Negativity in Predicting Young Children's Emotion Regulation and Socioemotional Difficulties

Science.gov (United States)

Maughan, Angeline; Cicchetti, Dante; Toth, Sheree L.; Rogosch, Fred A.

2007-01-01

This longitudinal investigation examined the effects of maternal depression and concomitant negative parenting behaviors on children's emotion regulation patterns and socioemotional functioning. One hundred fifty-one mothers and their children were assessed when children were approximately 1 1/2-, 3-, 4-, and 5-years of age. Ninety-three of the…

Radiation protection. Scientific fundamentals, legal regulations, practical applications. Compendium; Strahlenschutz. Wissenschaftliche Grundlagen, Rechtliche Regelungen, Praktische Anwendungen. Kompendium

Energy Technology Data Exchange (ETDEWEB)

Buchert, Guido; Gay, Juergen; Kirchner, Gerald; Michel, Rolf; Niggemann, Guenter; Schumann, Joerg; Wust, Peter; Jaehnert, Susanne; Strilek, Ralf; Martini, Ekkehard (eds.)

2011-06-15

The compendium on radiation protection, scientific fundamentals, legal regulations and practical applications includes contributions to the following issues: (1) Effects and risk of ionizing radiation: fundamentals on effects and risk of ionizing radiation, news in radiation biology, advantages and disadvantages of screening investigations; (2) trends and legal regulations concerning radiation protection: development of European and national radiation protection laws, new regulations concerning X-rays, culture and ethics of radiation protection; (3) dosimetry and radiation measuring techniques: personal scanning using GHz radiation, new ''dose characteristics'' in practice, measuring techniques for the nuclear danger prevention and emergency hazard control; (4) radiation exposure in medicine: radiation exposure of modern medical techniques, heavy ion radiotherapy, deterministic and stochastic risks of the high-conformal photon radiotherapy, STEMO project - mobile CT for apoplectic stroke patients; (5) radiation exposure in technology: legal control of high-level radioactive sources, technical and public safety using enclosed radioactive sources for materials testing, radiation exposure in aviation, radon in Bavaria, NPP Fukushima-Daiichi - a status report; (6) radiation exposure in nuclear engineering: The Chernobyl accident - historical experiences or sustaining problem? European standards for radioactive waste disposal, radioactive material disposal in Germany risk assessment of ionizing and non-ionizing radiation (7) Case studies.

Purification and Crystallization of Murine Myostatin: A Negative Regulator of Muscle Mass

Science.gov (United States)

Hong, Young S.; Adamek, Daniel; Bridge, Kristi; Malone, Christine C.; Young, Ronald B.; Miller, Teresa; Karr, Laurel

2004-01-01

Myostatin (MSTN) has been crystallized and its preliminary X-ray diffraction data were collected. MSTN is a negative regulator of muscle growt/differentiation and suppressor of fat accumulation. It is a member of TGF-b family of proteins. Like other members of this family, the regulation of MSTN is critically tied to its process of maturation. This process involves the formation of a homodimer followed by two proteolytic steps. The first proteolytic cleavage produces a species where the n-terminal portion of the dimer is covalently separated from, but remains non-covalently bound to, the c-terminal, functional, portion of the protein. The protein is activated upon removal of the n-terminal "pro-segment" by a second n-terminal proteolytic cut by BMP-1 in vivo, or by acid treatment in vitro. Understanding the structural nature and physical interactions involved in these regulatory processes is the objective of our studies. Murine MSTN was purified from culture media of genetically engineered Chinese Hamster Ovary cells by multicolumn purification process and crystallized using the vapor diffusion method.

Perfectionism and negative/positive affect associations: the role of cognitive emotion regulation and perceived distress/coping.

Science.gov (United States)

Castro, Juliana; Soares, Maria João; Pereira, Ana T; Macedo, António

2017-01-01

To explore 1) if perfectionism, perceived distress/coping, and cognitive emotion regulation (CER) are associated with and predictive of negative/positive affect (NA/PA); and 2) if CER and perceived distress/coping are associated with perfectionism and if they mediate the perfectionism-NA/PA associations. There is a distinction between maladaptive and adaptive perfectionism in its association with NA/PA. CER and perceived distress/coping may mediate the maladaptive/adaptive perfectionism and NA/PA associations. 344 students (68.4% girls) completed the Hewitt & Flett and the Frost Multidimensional Perfectionism Scales, the Composite Multidimensional Perfectionism Scale, the Profile of Mood States, the Perceived Stress Scale, and the Cognitive Emotion Regulation Questionnaire. NA predictors were maladaptive/adaptive perfectionism, maladaptive CER and perceived distress (positively), positive reappraisal and planning, and perceived coping (negatively). PA predictors were maladaptive/adaptive perfectionism and perceived distress (negatively), positive reappraisal and planning, positive refocusing and perceived coping (positively). The association between maladaptive perfectionism and NA was mediated by maladaptive CER/low adaptive CER, perceived distress/low coping. Maladaptive perfectionism and low PA association was mediated by perceived distress. High PA was determined by low maladaptive perfectionism and this association was mediated by adaptive REC and coping. Adaptive perfectionism and NA association was mediated by maladaptive CER and perceived distress. CER and perceived distress/coping are associated and mediate the perfectionism-NA/PA associations.

Reciprocal regulation of annexin A2 and EGFR with Her-2 in Her-2 negative and herceptin-resistant breast cancer.

Directory of Open Access Journals (Sweden)

Praveenkumar K Shetty

Full Text Available Alternative survival pathways are commonly seen to be upregulated upon inhibition of receptor tyrosine kinases (RTK, including Her-2. It is established that treatment with Herceptin leads to selective overexpression and activation of epidermal growth factor receptor (EGFR and Src which further contributes to oncogenesis in Herceptin resistant and triple negative breast cancer (TNBC patients. Here, we show a co-regulated upregulation in the expression of Annexin A2 (AnxA2, a known substrate of Src and one of the regulators of EGFR receptor endocytosis, in Herceptin resistant and Her-2 negative breast cancer. Immunohistochemical expression analysis revealed a reciprocal regulation between Her-2 and AnxA2 in breast cancer clinical samples as well as in cell lines as confirmed by protein and RNA analysis. The siRNA and Herceptin mediated downregulation/inhibition of Her-2 in Her-2 amplified cells induced AnxA2 expression and membrane translocation. In this study we report a possible involvement of AnxA2 in maintaining constitutively activated EGFR downstream signaling intermediates and hence in cell proliferation, migration and viability. This effect was consistent in Herceptin resistant JIMT-1 cells as well as in Her-2 negative breast cancer. The siRNA mediated AnxA2 downregulation leads to increased apoptosis, decreased cell viability and migration. Our studies further indicate the role of AnxA2 in EGFR-Src membrane bound signaling complex and ligand induced activation of downstream signaling pathways. Targeting this AnxA2 dependent positive regulation of EGFR signaling cascade may be of therapeutic value in Her-2 negative breast cancer.

Different Fear-Regulation Behaviors in Toddlerhood: Relations to Preceding Infant Negative Emotionality, Maternal Depression, and Sensitivity

Science.gov (United States)

Gloggler, Bettina; Pauli-Pott, Ursula

2008-01-01

In the study presented, the development of different fear regulation behaviors and their associations with preceding maternal sensitivity and depression is addressed. A sample of 64 mother-child pairs was examined at the children's ages of 4, 12, and 30 months. Four-month negative reactivity and 12- and 30- month behavioral inhibition and fear…

Revised technical regulations on radiation protection and safety of 30 September 1975

International Nuclear Information System (INIS)

1975-01-01

These revised technical regulations were made in implementation of Section 4 of Decree No 7/9038 of 30 November 1974 on radiation health and safety and lay down in detail the requirements to be met in Turkey for the use of all types of radiation sources. They set out protection plans and specify the protective equipment to be used as well as the controlled areas, i.e. areas in which radiation sources are used and which must be subject to special safety measures. Finally to obtain a license, users of radiation sources must fill in forms, the models of which are provided, giving their particulars and the specifications of the intended use and activity of the sources. (NEA) [fr

Online Gambling Advertising Regulations in Spain. A Study on the Protection of Minors.

Science.gov (United States)

Buil, Pilar; Solé Moratilla, Maria José; García Ruiz, Pablo

2015-09-15

This article examines the online gambling advertising regulations in Spain currently in effect to assess the actual protection of underage youth. In recent years, online gambling among youth has increased. Through advertising, online gambling companies incite and encourage an involvement that can be harmful for vulnerable audiences. Some studies have demonstrated that advertising influences youths' assessment of gambling by increasing its appeal. We demonstrate that the shortcomings of the legal framework in force results in effective vulnerability of minors. We claim that society should seek to implement a regulatory framework to protect children from the risk of developing an addiction.

Negative regulation of human parathyroid hormone gene promoter by vitamin D3 through nuclear factor Y

International Nuclear Information System (INIS)

Jaeaeskelaeinen, T.; Huhtakangas, J.; Maeenpaeae, P.H.

2005-01-01

The negative regulation of the human parathyroid hormone (PTH) gene by biologically active vitamin D 3 (1,25-dihydroxyvitamin D 3 ; 1,25(OH) 2 D 3 ) was studied in rat pituitary GH4C1 cells, which express factors needed for the negative regulation. We report here that NF-Y binds to sequences downstream of the site previously reported to bind the vitamin D receptor (VDR). Additional binding sites for NF-Y reside in the near vicinity and were shown to be important for full activity of the PTH gene promoter. VDR and NF-Y were shown to exhibit mutually exclusive binding to the VDRE region. According to our results, sequestration of binding partners for NF-Y by VDR also affects transcription through a NF-Y consensus binding element in GH4C1 but not in ROS17/2.8 cells. These results indicate that 1,25(OH) 2 D 3 may affect transcription of the human PTH gene both by competitive binding of VDR and NF-Y, and by modulating transcriptional activity of NF-Y

Small kinetochore associated protein (SKAP promotes UV-induced cell apoptosis through negatively regulating pre-mRNA processing factor 19 (Prp19.

Directory of Open Access Journals (Sweden)

Shan Lu

Full Text Available Apoptosis is a regulated cellular suicide program that is critical for the development and maintenance of healthy tissues. Previous studies have shown that small kinetochore associated protein (SKAP cooperates with kinetochore and mitotic spindle proteins to regulate mitosis. However, the role of SKAP in apoptosis has not been investigated. We have identified a new interaction involving SKAP, and we propose a mechanism through which SKAP regulates cell apoptosis. Our experiments demonstrate that both overexpression and knockdown of SKAP sensitize cells to UV-induced apoptosis. Further study has revealed that SKAP interacts with Pre-mRNA processing Factor 19 (Prp19. We find that UV-induced apoptosis can be inhibited by ectopic expression of Prp19, whereas silencing Prp19 has the opposite effect. Additionally, SKAP negatively regulates the protein levels of Prp19, whereas Prp19 does not alter SKAP expression. Finally, rescue experiments demonstrate that the pro-apoptotic role of SKAP is executed through Prp19. Taken together, these findings suggest that SKAP promotes UV-induced cell apoptosis by negatively regulating the anti-apoptotic protein Prp19.

Endoglin negatively regulates transforming growth factor beta1-induced profibrotic responses in intestinal fibroblasts.

LENUS (Irish Health Repository)

Burke, J P

2012-02-01

BACKGROUND: Fibroblasts isolated from strictures in Crohn\\'s disease (CD) exhibit reduced responsiveness to stimulation with transforming growth factor (TGF) beta1. TGF-beta1, acting through the smad pathway, is critical to fibroblast-mediated intestinal fibrosis. The membrane glycoprotein, endoglin, is a negative regulator of TGF-beta1. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies of patients undergoing intestinal resection for CD strictures or from control patients. Endoglin expression was assessed using confocal microscopy, flow cytometry and western blot. The effect of small interfering (si) RNA-mediated knockdown and plasmid-mediated overexpression of endoglin on fibroblast responsiveness to TGF-beta1 was assessed by examining smad phosphorylation, smad binding element (SBE) promoter activity, connective tissue growth factor (CTGF) expression and ability to contract collagen. RESULTS: Crohn\\'s stricture fibroblasts expressed increased constitutive cell-surface and whole-cell endoglin relative to control cells. Endoglin co-localized with filamentous actin. Fibroblasts treated with siRNA directed against endoglin exhibited enhanced TGF-beta1-mediated smad-3 phosphorylation, and collagen contraction. Cells transfected with an endoglin plasmid did not respond to TGF-beta1 by exhibiting SBE promoter activity or producing CTGF. CONCLUSION: Fibroblasts from strictures in CD express increased constitutive endoglin. Endoglin is a negative regulator of TGF-beta1 signalling in the intestinal fibroblast, modulating smad-3 phosphorylation, SBE promoter activity, CTGF production and collagen contraction.

proBDNF Negatively Regulates Neuronal Remodeling, Synaptic Transmission, and Synaptic Plasticity in Hippocampus

Directory of Open Access Journals (Sweden)

Jianmin Yang

2014-05-01

Full Text Available Experience-dependent plasticity shapes postnatal development of neural circuits, but the mechanisms that refine dendritic arbors, remodel spines, and impair synaptic activity are poorly understood. Mature brain-derived neurotrophic factor (BDNF modulates neuronal morphology and synaptic plasticity, including long-term potentiation (LTP via TrkB activation. BDNF is initially translated as proBDNF, which binds p75NTR. In vitro, recombinant proBDNF modulates neuronal structure and alters hippocampal long-term plasticity, but the actions of endogenously expressed proBDNF are unclear. Therefore, we generated a cleavage-resistant probdnf knockin mouse. Our results demonstrate that proBDNF negatively regulates hippocampal dendritic complexity and spine density through p75NTR. Hippocampal slices from probdnf mice exhibit depressed synaptic transmission, impaired LTP, and enhanced long-term depression (LTD in area CA1. These results suggest that proBDNF acts in vivo as a biologically active factor that regulates hippocampal structure, synaptic transmission, and plasticity, effects that are distinct from those of mature BDNF.

SarA is a negative regulator of Staphylococcus epidermidis biofilm formation

DEFF Research Database (Denmark)

Martin, Christer; Heinze, C.; Busch, M.

2012-01-01

Biofilm formation is essential for Staphylococcus epidermidis pathogenicity in implant-associated infections. Nonetheless, large proportions of invasive S. epidermidis isolates fail to show accumulative biofilm growth in vitro. We here tested the hypothesis that this apparent paradox is related...... virulence. Genetic analysis revealed that inactivation of sarA induced biofilm formation via over-expression of the giant 1 MDa extracellular matrix binding protein (Embp), serving as an intercellular adhesin. In addition to Embp, increased extracellular DNA (eDNA) release significantly contributed...... to biofilm formation in mutant 1585ΔsarA. Increased eDNA amounts indirectly resulted from up-regulation of metalloprotease SepA, leading to boosted processing of major autolysin AtlE, in turn inducing augmented autolysis and release of chromosomal DNA. Hence, this study identifies sarA as a negative...

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

Science.gov (United States)

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

2017-12-01

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

Models of Aire-dependent gene regulation for thymic negative selection

Directory of Open Access Journals (Sweden)

Dina eDanso-Abeam

2011-05-01

Full Text Available Mutations in the Autoimmune Regulator (AIRE gene lead to Autoimmune Polyendocrinopathy Syndrome type 1 (APS1, characterized by the development of multi-organ autoimmune damage. The mechanism by which defects in AIRE result in autoimmunity has been the subject of intense scrutiny. At the cellular level, the working model explains most of the clinical and immunological characteristics of APS1, with AIRE driving the expression of tissue restricted antigens (TRAs in the epithelial cells of the thymic medulla. This TRA expression results in effective negative selection of TRA-reactive thymocytes, preventing autoimmune disease. At the molecular level, the mechanism by which AIRE initiates TRA expression in the thymic medulla remains unclear. Multiple different models for the molecular mechanism have been proposed, ranging from classical transcriptional activity, to random induction of gene expression, to epigenetic tag recognition effect, to altered cell biology. In this review, we evaluate each of these models and discuss their relative strengths and weaknesses.

The trans-kingdom identification of negative regulators of pathogen hypervirulence.

Science.gov (United States)

Brown, Neil A; Urban, Martin; Hammond-Kosack, Kim E

2016-01-01

Modern society and global ecosystems are increasingly under threat from pathogens, which cause a plethora of human, animal, invertebrate and plant diseases. Of increasing concern is the trans-kingdom tendency for increased pathogen virulence that is beginning to emerge in natural, clinical and agricultural settings. The study of pathogenicity has revealed multiple examples of convergently evolved virulence mechanisms. Originally described as rare, but increasingly common, are interactions where a single gene deletion in a pathogenic species causes hypervirulence. This review utilised the pathogen-host interaction database (www.PHI-base.org) to identify 112 hypervirulent mutations from 37 pathogen species, and subsequently interrogates the trans-kingdom, conserved, molecular, biochemical and cellular themes that cause hypervirulence. This study investigates 22 animal and 15 plant pathogens including 17 bacterial and 17 fungal species. Finally, the evolutionary significance and trans-kingdom requirement for negative regulators of hypervirulence and the implication of pathogen hypervirulence and emerging infectious diseases on society are discussed. © FEMS 2015.

Lack of Csk-mediated negative regulation in a unicellular SRC kinase.

Science.gov (United States)

Schultheiss, Kira P; Suga, Hiroshi; Ruiz-Trillo, Iñaki; Miller, W Todd

2012-10-16

Phosphotyrosine-based signaling plays a vital role in cellular communication in multicellular organisms. Unexpectedly, unicellular choanoflagellates (the closest phylogenetic group to metazoans) possess numbers of tyrosine kinases that are comparable to those in complex metazoans. Here, we have characterized tyrosine kinases from the filasterean Capsaspora owczarzaki, a unicellular protist representing the sister group to choanoflagellates and metazoans. Two Src-like tyrosine kinases have been identified in C. owczarzaki (CoSrc1 and CoSrc2), both of which have the arrangement of SH3, SH2, and catalytic domains seen in mammalian Src kinases. In Capsaspora cells, CoSrc1 and CoSrc2 localize to punctate structures in filopodia that may represent primordial focal adhesions. We have cloned, expressed, and purified both enzymes. CoSrc1 and CoSrc2 are active tyrosine kinases. Mammalian Src kinases are normally regulated in a reciprocal fashion by autophosphorylation in the activation loop (which increases activity) and by Csk-mediated phosphorylation of the C-terminal tail (which inhibits activity). Similar to mammalian Src kinases, the enzymatic activities of CoSrc1 and CoSrc2 are increased by autophosphorylation in the activation loop. We have identified a Csk-like kinase (CoCsk) in the genome of C. owczarzaki. We cloned, expressed, and purified CoCsk and found that it has no measurable tyrosine kinase activity. Furthermore, CoCsk does not phosphorylate or regulate CoSrc1 or CoSrc2 in cells or in vitro, and CoSrc1 and CoSrc2 are active in Capsaspora cell lysates. Thus, the function of Csk as a negative regulator of Src family kinases appears to have arisen with the emergence of metazoans.

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Acid Sphingomyelinase (ASM) is a Negative Regulator of Regulatory T Cell (Treg) Development.

Science.gov (United States)

Zhou, Yuetao; Salker, Madhuri S; Walker, Britta; Münzer, Patrick; Borst, Oliver; Gawaz, Meinrad; Gulbins, Erich; Singh, Yogesh; Lang, Florian

2016-01-01

Regulatory T cell (Treg) is required for the maintenance of tolerance to various tissue antigens and to protect the host from autoimmune disorders. However, Treg may, indirectly, support cancer progression and bacterial infections. Therefore, a balance of Treg function is pivotal for adequate immune responses. Acid sphingomyelinase (ASM) is a rate limiting enzyme involved in the production of ceramide by breaking down sphingomyelin. Previous studies in T-cells have suggested that ASM is involved in CD28 signalling, T lymphocyte granule secretion, degranulation, and vesicle shedding similar to the formation of phosphatidylserine-exposing microparticles from glial cells. However, whether ASM affects the development of Treg has not yet been described. Splenocytes, isolated Naive T lymphocytes and cultured T cells were characterized for various immune T cell markers by flow cytometery. Cell proliferation was measured by Carboxyfluorescein succinimidyl ester (CFSE) dye, cell cycle analysis by Propidium Iodide (PI), mRNA transcripts by q-RT PCR and protein expression by Western Blotting respectively. ASM deficient mice have higher number of Treg compared with littermate control mice. In vitro induction of ASM deficient T cells in the presence of TGF-β and IL-2 lead to a significantly higher number of Foxp3+ induced Treg (iTreg) compared with control T-cells. Further, ASM deficient iTreg has less AKT (serine 473) phosphorylation and Rictor levels compared with control iTreg. Ceramide C6 led to significant reduction of iTreg in both ASM deficient and WT mice. The reduction in iTreg leads to induction of IL-1β, IL-6 and IL-17 but not IFN-γ mRNA levels. ASM is a negative regulator of natural and iTreg. © 2016 The Author(s) Published by S. Karger AG, Basel.

Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders

OpenAIRE

Gery, Sigal; Gueller, Saskia; Chumakova, Katya; Kawamata, Norihiko; Liu, Liqin; Koeffler, H. Phillip

2007-01-01

Recently, activating myeloproliferative leukemia virus oncogene (MPL) mutations, MPLW515L/K, were described in myeloproliferative disorder (MPD) patients. MPLW515L leads to activation of downstream signaling pathways and cytokine-independent proliferation in hematopoietic cells. The adaptor protein Lnk is a negative regulator of several cytokine receptors, including MPL. We show that overexpression of Lnk in Ba/F3-MPLW515L cells inhibits cytokine-independent growth, while suppression of Lnk i...

Establishment and maintenance of regulating ecosystem services in a dryland area of central Asia, illustrated using the Kökyar Protection Forest, Aksu, NW China, as an example

Science.gov (United States)

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.

Mines Safety Control (Radiation Protection) Regulations (Northern Territory) No. 30 of 25 September 1981

International Nuclear Information System (INIS)

1981-01-01

These Regulations, pursuant to the Mines Safety Control Act, are intended to prevent or limit the radiation risk to persons involved in the mining or milling of radioactive ores. The duties and responsibilities imposed by the Regulations on owners, managers and employees of the mines are identical with those set forth in the 1980 Code of Practice on Radiation Protection in the Mining and Milling of Radioactive Ores which establishes radiation standards and exposure limits, requires health surveillance of employees and provides for the management of radioactive wastes. (NEA) [fr

Radiation protection: Scientific fundamentals, legal regulations, practical applications. Compendium. 8. ed.

International Nuclear Information System (INIS)

Buchert, G.; Czarwinski, R.; Martini, E.; Ruehle, H.; Wust, P.

2003-01-01

In 2003, radiation effects and radiation risks were again a central issue, with new biokinetic and dosimetric models. Preliminary experience with new legal regulations on radiation protection was a central issue. Dosimetry and radiation protection metrology were gone into, as was radiation exposure in medicine, engineering, and the environment. New diagnostic methods in medicine were presented, and radiation exposures resulting from some of these techniques were analyzed. Industrial applications of ionising radiation and technical radiography were presented. Nuclear engineering was covered as well, e.g. how to maintain the current know-how after the agreed nuclear phase-out, the transport of spent fuel elements, and the safety of nuclear power stations in eastern Europe. As in the years before, detection limits in radiation measurement, calculations of radiation exposure, incidents in nuclear facilities, and radiation exposure assessment after safety-relevant incidents were among the issues discussed. (orig.)

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

Science.gov (United States)

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

2015-05-17

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

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

Science.gov (United States)

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

2016-01-01

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

The moderating effects of aging and cognitive abilities on the association between work stress and negative affect.

Science.gov (United States)

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.

Regulation requirements for the protection of workers against electromagnetic fields occurring in the work environment

International Nuclear Information System (INIS)

Aniolczyk, H.; Zmyslony, M.

2006-01-01

In Poland, electromagnetic fields (EMF), one of potentially hazardous physical factors occurring in the work environment, are subjected to compulsory surveillance. In 2001, the Directive issued by the Minister of Labor and Social Policy substantially changed the approach towards the protection of workers against EMF. The Directive regulates the whole range of EMF frequencies and electromagnetic radiation, namely from 0 Hz to 300 GHz, which means the possibility of assessing workers EMF exposure, determined by exposure index, along with the hygiene assessment of EMF sources, defined by protection zones. In 2003 - 2005, a number of amended executive and supplementary regulations were issued. However, it should be emphasized that in the process of their elaboration, striving after perfection, numerous incoherent and ambiguous provisions were adopted, which finally created difficulties in the interpretation of individual regulations. This is also linked with doubts and discussions on their practical application by services responsible for control, measurements and monitoring of working conditions under the exposure to EMF. In this work an attempt was made to clarify all issues and arrange them according to the faced problems. The authors also present proposals how to solve all these problems. (author)

Radiation protection: Principles, recommendations and regulations

International Nuclear Information System (INIS)

Reitan, J.B.

1989-01-01

Radiation protection is a highly international dicipline with a high degree of international harmonization. Especially within the Nordic countries there is general agreement upon principles and standards, despite the actual practice may differ slightly. The basic recommendations of the International Commission on Radiological Protection (ICRP) are accepted by the regulatory bodies and should be followed by all users of radiation. The users are in principle responsible for the radiation protection standard and activities themselves. Because most companies or hospitals lack sufficient expertise by themselves, they must rely upon recommendations from others. Primarily they should contact the national radiation protection agency. However, due to the international harmonization of radiation protection, information from other national or international agencies may be used with confidence. All users of radiation in the Nordic countries are obliged to act according to recognition and assessment of both risks and benefits, and they are responsible for updating their knowledge

From regulations towards radiation protection culture

International Nuclear Information System (INIS)

Boehler, M.C.

1996-01-01

Compliance with the technical standards and specifications is a necessary but not sufficient condition for quality in radiation protection. Reaching this quality objective is not a matter of forcing improvements by a regulatory policy of reducing dose limits, but of promoting a real radiation protection culture. The spread of such a radiological protection culture encourages the deliberate adoption in everyday practice of behaviour likely to reduce exposure to ionizing radiation as loser as reasonably achievable. The aim of this paper is to demonstrate that the need to diffuse a radiological protection culture is inspired by the philosophy behind the system recommended by ICPR Publication 60 on the management of residual radiological risk and, in particular by the behavioural and incentive approach implied by the optimization principle. Special attention will be given to the fundamentals likely to contribute in a definition of radiation protection culture. (author)

Unkempt is negatively regulated by mTOR and uncouples neuronal differentiation from growth control.

Directory of Open Access Journals (Sweden)

Amélie Avet-Rochex

2014-09-01

Full Text Available Neuronal differentiation is exquisitely controlled both spatially and temporally during nervous system development. Defects in the spatiotemporal control of neurogenesis cause incorrect formation of neural networks and lead to neurological disorders such as epilepsy and autism. The mTOR kinase integrates signals from mitogens, nutrients and energy levels to regulate growth, autophagy and metabolism. We previously identified the insulin receptor (InR/mTOR pathway as a critical regulator of the timing of neuronal differentiation in the Drosophila melanogaster eye. Subsequently, this pathway has been shown to play a conserved role in regulating neurogenesis in vertebrates. However, the factors that mediate the neurogenic role of this pathway are completely unknown. To identify downstream effectors of the InR/mTOR pathway we screened transcriptional targets of mTOR for neuronal differentiation phenotypes in photoreceptor neurons. We identified the conserved gene unkempt (unk, which encodes a zinc finger/RING domain containing protein, as a negative regulator of the timing of photoreceptor differentiation. Loss of unk phenocopies InR/mTOR pathway activation and unk acts downstream of this pathway to regulate neurogenesis. In contrast to InR/mTOR signalling, unk does not regulate growth. unk therefore uncouples the role of the InR/mTOR pathway in neurogenesis from its role in growth control. We also identified the gene headcase (hdc as a second downstream regulator of the InR/mTOR pathway controlling the timing of neurogenesis. Unk forms a complex with Hdc, and Hdc expression is regulated by unk and InR/mTOR signalling. Co-overexpression of unk and hdc completely suppresses the precocious neuronal differentiation phenotype caused by loss of Tsc1. Thus, Unk and Hdc are the first neurogenic components of the InR/mTOR pathway to be identified. Finally, we show that Unkempt-like is expressed in the developing mouse retina and in neural stem

GlnR-Mediated Regulation of ectABCD Transcription Expands the Role of the GlnR Regulon to Osmotic Stress Management.

Science.gov (United States)

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.

The German Radiation Protection Ordinance of 2000: a survey and comparison with the former regulations

International Nuclear Information System (INIS)

Wolf, H.

2000-01-01

The radiation protection standards defined by the European Union in May 1996, as well as the EU directive for the protection of patients, effective since June 1997, have to be incorporated into the law and administrative regulations of the Federal Republic of Germany by the 13th of May 2000. The German BMU, the ministry responsible for nuclear safety and radiation protection, presented the draft law for departmental consultation about the amendment of the StlSchV in December 1999. This draft law is the basis of the expert discussions of the meeting. One major change for instance is that for the first time, a broad classification system has been applied, which facilitates orientation. (orig./CB) [de

The effect of the social regulation of emotion on emotional long-term memory.

Science.gov (United States)

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).

Abscisic acid negatively regulates post-penetration resistance of Arabidopsis to the biotrophic powdery mildew fungus.

Science.gov (United States)

Xiao, Xiang; Cheng, Xi; Yin, Kangquan; Li, Huali; Qiu, Jin-Long

2017-08-01

Pytohormone abscisic acid (ABA) plays important roles in defense responses. Nonetheless, how ABA regulates plant resistance to biotrophic fungi remains largely unknown. Arabidopsis ABA-deficient mutants, aba2-1 and aba3-1, displayed enhanced resistance to the biotrophic powdery mildew fungus Golovinomyces cichoracearum. Moreover, exogenously administered ABA increased the susceptibility of Arabidopsis to G. cichoracearum. Arabidopsis ABA perception components mutants, abi1-1 and abi2-1, also displayed similar phenotypes to ABA-deficient mutants in resistance to G. cichoracearum. However, the resistance to G. cichoracearum is not changed in downstream ABA signaling transduction mutants, abi3-1, abi4-1, and abi5-1. Microscopic examination revealed that hyphal growth and conidiophore production of G. cichoracearum were compromised in the ABA deficient mutants, even though pre-penetration and penetration growth of the fungus were not affected. In addition, salicylic acid (SA) and MPK3 are found to be involved in ABA-regulated resistance to G. cichoracearum. Our work demonstrates that ABA negatively regulates post-penetration resistance of Arabidopsis to powdery mildew fungus G. cichoracearum, probably through antagonizing the function of SA.

Functional analysis of Arabidopsis immune-related MAPKs uncovers a role for MPK3 as negative regulator of inducible defences

KAUST Repository

Frei dit Frey, Nicolas; Garcia, Ana; Bigeard, Jean; Zaag, Rim; Bueso, Eduardo; Garmier, Marie; Pateyron, Sté phanie; de Tauzia-Moreau, Marie-Ludivine; Brunaud, Vé ronique; Balzergue, Sandrine; Colcombet, Jean; Aubourg, Sé bastien; Martin-Magniette, Marie-Laure; Hirt, Heribert

2014-01-01

-induced genes and we identify a negative role for MPK3 in regulating defence gene expression, flg22-induced salicylic acid accumulation and disease resistance to Pseudomonas syringae. Among the MAPK-dependent genes, 27% of flg22-upregulated genes and 76

TRAF family member-associated NF-κB activator (TANK) induced by RANKL negatively regulates osteoclasts survival and function.

Science.gov (United States)

Wu, Mengrui; Wang, Yiping; Deng, Lianfu; Chen, Wei; Li, Yi-Ping

2012-01-01

Osteoclasts are the principle bone-resorbing cells. Precise control of balanced osteoclast activity is indispensable for bone homeostasis. Osteoclast activation mediated by RANK-TRAF6 axis has been clearly identified. However, a negative regulation-machinery in osteoclast remains unclear. TRAF family member-associated NF-κB activator (TANK) is induced by about 10 folds during osteoclastogenesis, according to a genome-wide analysis of gene expression before and after osteoclast maturation, and confirmed by western blot and quantitative RT-PCR. Bone marrow macrophages (BMMs) transduced with lentivirus carrying tank-shRNA were induced to form osteoclast in the presence of RANKL and M-CSF. Tank expression was downregulated by 90% by Tank-shRNA, which is confirmed by western blot. Compared with wild-type (WT) cells, osteoclastogenesis of Tank-silenced BMMs was increased, according to tartrate-resistant acid phosphatase (TRAP) stain on day 5 and day 7. Number of bone resorption pits by Tank-silenced osteoclasts was increased by 176% compared with WT cells, as shown by wheat germ agglutinin (WGA) stain and scanning electronic microscope (SEM) analysis. Survival rate of Tank-silenced mature osteoclast is also increased. However, acid production of Tank-knockdown cells was not changed compared with control cells. IκBα phosphorylation is increased in tank-silenced cells, indicating that TANK may negatively regulate NF-κB activity in osteoclast. In conclusion, Tank, whose expression is increased during osteoclastogenesis, inhibits osteoclast formation, activity and survival, by regulating NF-κB activity and c-FLIP expression. Tank enrolls itself in a negative feedback loop in bone resorption. These results may provide means for therapeutic intervention in diseases of excessive bone resorption.

Elongated Hypocotyl 5-Homolog (HYH Negatively Regulates Expression of the Ambient Temperature-Responsive MicroRNA Gene MIR169

Directory of Open Access Journals (Sweden)

Phanu T. Serivichyaswat

2017-12-01

Full Text Available Arabidopsis microRNA169 (miR169 is an ambient temperature-responsive microRNA that plays an important role in stress responses and the floral transition. However, the transcription factors that regulate the expression of MIR169 have remained unknown. In this study, we show that Elongated Hypocotyl 5-Homolog (HYH directly binds to the promoter of MIR169a and negatively regulates its expression. Absolute quantification identified MIR169a as the major locus producing miR169. GUS reporter assays revealed that the deletion of a 498-bp fragment (–1,505 to –1,007, relative to the major transcriptional start site of MIR169a abolished its ambient temperature-responsive expression. DNA-affinity chromatography followed by liquid chromatography-mass spectrometry analysis identified transcription factor HYH as a trans-acting factor that binds to the 498-bp promoter fragment of pri-miR169a. Electrophoretic mobility shift assays and chromatin immunoprecipitation–quantitative PCR demonstrated that the HYH.2 protein, a predominant isoform of HYH, directly associated with a G-box-like motif in the 498-bp fragment of pri-miR169a. Higher enrichment of HYH.2 protein on the promoter region of MIR169a was seen at 23°C, consistent with the presence of more HYH.2 protein in the cell at the temperature. Transcript levels of pri-miR169a increased in hyh mutants and decreased in transgenic plants overexpressing HYH. Consistent with the negative regulation of MIR169a by HYH, the diurnal levels of HYH mRNA and pri-miR169a showed opposite patterns. Taken together, our results suggest that HYH is a transcription factor that binds to a G-box-like motif in the MIR169a promoter and negatively regulates ambient temperature-responsive expression of MIR169a at higher temperatures in Arabidopsis.

Salt Stress Represses Soybean Seed Germination by Negatively Regulating GA Biosynthesis While Positively Mediating ABA Biosynthesis

OpenAIRE

Kai Shu; Ying Qi; Feng Chen; Yongjie Meng; Xiaofeng Luo; Haiwei Shuai; Wenguan Zhou; Jun Ding; Junbo Du; Jiang Liu; Feng Yang; Qiang Wang; Weiguo Liu; Taiwen Yong; Xiaochun Wang

2017-01-01

Soybean is an important and staple oilseed crop worldwide. Salinity stress has adverse effects on soybean development periods, especially on seed germination and post-germinative growth. Improving seed germination and emergence will have positive effects under salt stress conditions on agricultural production. Here we report that NaCl delays soybean seed germination by negatively regulating gibberellin (GA) while positively mediating abscisic acid (ABA) biogenesis, which leads to a decrease i...

Defective interleukin-4/Stat6 activity correlates with increased constitutive expression of negative regulators SOCS-3, SOCS-7, and CISH in colon cancer cells.

Science.gov (United States)

Liu, Xiao Hong; Xu, Shuang Bing; Yuan, Jia; Li, Ben Hui; Zhang, Yan; Yuan, Qin; Li, Pin Dong; Li, Feng; Zhang, Wen Jie

2009-12-01

Interleukin-4 (IL-4)-induced Stat6 activities (phenotypes) vary among human cancer cells, of which the HT-29 cell line carries an active Stat6(high) phenotype, while Caco-2 carries a defective Stat6(null) phenotype, respectively. Cancer cells with Stat6(high) show resistance to apoptosis and exaggerated metastasis, suggesting the clinical significance of Stat6 phenotypes. We previously showed that Stat6(high) HT-29 cells exhibited low constitutive expression of Stat6-negative regulators SOCS-1 and SHP-1 because of gene hypermethylation. This study further examined the constitutive expression of other closely related SOCS family numbers including SOCS-3, SOCS-5, SOCS-7, and CISH using RT-PCR. Similar to SOCS-1 and SHP-1, Stat6(high) HT-29 cells expressed low constitutive mRNA of SOCS-3, SOCS-7, and CISH than Stat6(null) Caco-2 cells. Interestingly, DNA demethylation using 5-aza-2'-deoxycytidine in HT-29 cells up-regulated mRNA expression of the above genes, indicating a hypermethylation status, which was confirmed by methylation-specific sequencing in selected SOCS-3 gene. Furthermore, defective Stat6(null) Caco-2 exhibited impaired phosphorylation of Stat6 after IL-4 stimulation by flow cytometry, in keeping with the notion of an over-performed negative regulation. The findings that IL-4/Stat6 phenotypes show differential expression of multiple negative regulators suggest a model that a collective force of powerful negative regulators, directly and indirectly, acts on Stat6 activation, which may result in differential Stat6 phenotypes.

Predictive Effects of Good Self-Control and Poor Regulation on Alcohol-Related Outcomes: Do Protective Behavioral Strategies Mediate?

Science.gov (United States)

Pearson, Matthew R.; Kite, Benjamin A.; Henson, James M.

2016-01-01

In the present study, we examined whether use of protective behavioral strategies mediated the relationship between self-control constructs and alcohol-related outcomes. According to the two-mode model of self-control, good self-control (planfulness; measured with Future Time Perspective, Problem Solving, and Self-Reinforcement) and poor regulation (impulsivity; measured with Present Time Perspective, Poor Delay of Gratification, Distractibility) are theorized to be relatively independent constructs rather than opposite ends of a single continuum. The analytic sample consisted of 278 college student drinkers (68% women) who responded to a battery of surveys at a single time point. Using a structural equation model based on the two-mode model of self-control, we found that good self-control predicted increased use of three types of protective behavioral strategies (Manner of Drinking, Limiting/Stopping Drinking, and Serious Harm Reduction). Poor regulation was unrelated to use of protective behavioral strategies, but had direct effects on alcohol use and alcohol problems. Further, protective behavioral strategies mediated the relationship between good self-control and alcohol use. The clinical implications of these findings are discussed. PMID:22663345

Strict Liability Versus Policy and Regulation for Environmental Protection and Agricultural Waste Management in Malaysia

Directory of Open Access Journals (Sweden)

Mohd Bakri Ishak

2010-01-01

Full Text Available Basically, strict liability is part of the mechanism for expressing judgment or sentence by using direct evidence. This principle is very useful in order to obtain remedies from any damage either directly or indirectly. The principle in Rylands v Fletcher is responsible on imposing strict liability where if something brought onto land or collected there escapes liability under this rule can include not only the owner of land but also those who control or occupation on it. However, as a matter of fact, policy and regulation are also important in taking any action against any party who are responsible for environmental pollution or damage, which may include mismanagement of waste or industrial waste or agricultural waste. There are certain policies and regulations on environmental protection such as the National Environmental Policy, certain Acts and several regulations under the Environmental Quality Act 1974 (Act 127, which are very useful for agricultural waste management inter alia: Waters Act 1920 (Act 418, Environmental Quality (Prescribed Premises (Crude Palm Oil Regulations 1977, Environmental Quality (Prescribed Premises (Raw Natural Rubber Regulations 1978, Environmental Quality (Sewage and Industrial Effluents Regulations 1979, and Environmental Quality (Compounding of Offences Rules 1978. As a matter of fact, we should realize that time is of an essence for any parties which are involved in court cases and especially in avoiding the element of externality, which is commonly suffered by the government. In making this paper, therefore, some element of comparison with certain developed jurisdiction such as in the United Kingdom and Japan could not be avoided in order to obtain better outcome and to be more practical for the purpose of environmental protection and agricultural waste management.

Achieving Negative CO2 Emissions by Protecting Ocean Chemistry

Science.gov (United States)

Cannara, A.

2016-12-01

Industrial Age CO2 added 1.8 trillion tons to the atmosphere. About ¼ has dissolved in seas. The rest still dissolves, bolstered by present emissions of >30 gigatons/year. Airborne & oceanic CO2 have induced sea warming & ocean acidification*. This paper suggests a way to induce a negative CO2-emissions environment for climate & oceans - preserve the planet`s dominant CO2-sequestration system ( 1 gigaton/year via calcifying sea life**) by promptly protecting ocean chemistry via expansion of clean power for both lime production & replacement of CO2-emitting sources. Provide natural alkali (CaO, MgO…) to oceans to maintain average pH above 8.0, as indicated by marine biologists. That alkali (lime) is available from past calcifying life's limestone deposits, so can be returned safely to seas once its CO2 is removed & permanently sequestered (Carbfix, BSCP, etc.***). Limestone is a dense source of CO2 - efficient processing per mole sequestered. Distribution of enough lime is possible via cargo-ship transits - 10,000 tons lime/transit, 1 million transits/year. New Panamax ships carry 120,000 tons. Just 10,000/transit allows gradual reduction of present & past CO2 emissions effects, if coupled with combustion-power reductions. CO2 separation from limestone, as in cement plants, consumes 400kWHrs of thermal energy per ton of output lime (or CO2). To combat yearly CO2 dissolution in seas, we must produce & distribute about 10gigatons of lime/year. Only nuclear power produces the clean energy (thousands of terawatt hours) to meet this need - 1000 dedicated 1GWe reactors, processing 12 cubic miles of limestone/year & sequestering CO2 into a similar mass of basalt. Basalt is common in the world. Researchers*** report it provides good, mineralized CO2 sequestration. The numbers above allow gradual CO2 reduction in air and seas, if we return to President Kennedy's energy path: http://tinyurl.com/6xgpkfa We're on an environmental precipice due to failure to eliminate

Review of current and anticipated regulations on air protection in the Czech Republic

Energy Technology Data Exchange (ETDEWEB)

Jilek, P.; Novotny, V. [Ministry of the Environment of the Czech Republic, Prague (Czechoslovakia)

1995-12-01

Environmental issues, especially the solution of the air pollution problem, have taken on great significance in the Czech Republic (which was a part of the Czech and Slovak Federal Republic until the end of 1992) since the 1989 {open_quotes}Velvet{close_quotes} Revolution. The former CSFR Federal Committee for the Environment and both the Republic Ministries started immediately with creating new environmental legislation, which is the main governmental tool for protecting the environment in the newly developing democracy state system with a market oriented economy. The inspiration for that activity was found in legislation of developed countries - member states of the European Union, and in German environmental law in particular. This paper surveys the major laws and regulations that gradually came into force in the Czech Republic since 1990. The provisions of the primary significance are the Act No.309/1991 S.B., dated July 9, 1991, on the protection of the air against pollutants - The Clean Air Act, the Act No.218/1992 S.B., dated April 27, 1992, which changes and supplements the Act No.309 - The Clean Air Act, the Measure of the Federal Committee for the Environment of October 1, 1991 to the Clean Air Act, and its amended wordings of June 23, 1992, 84/1991 S.B., and 84/1992 S.B., the Act No.389/1991 S.B., dated September 10, 1991 on the state administration of air protection and charges for the pollution of air, and several regulations based on the Act No.389/1991 S.B., issued in the period 1992 -1993.

Conflicting paradigms in radiation protection: 20 Questions with answers from the regulator, the health physicist, the scientist, and the lawyers

International Nuclear Information System (INIS)

Strom, D.J.; Stansbury, P.S.; Porter, S.W. Jr.

1995-01-01

George Orwell's open-quotes doublethinkclose quotes should be generalized to open-quotes polythinkclose quotes to describe the multiplicity of views that radiation protection professionals must simultaneously accommodate. The paradigms, that is, organizing principles and beliefs, that (1) regulators, (2) operational health physicists, (3) scientists, (4) lawyers for the defendant, and (5) lawyers for the plaintiff use in their approaches to radiation protection are presented. What we believe as scientists often conflicts with what we do for purposes of radiation protection. What we need to do merely to protect humankind and the environment from harmful effects of radiation is far less than what we must do to satisfy the regulator, whose paradigm has checklists, score-keeping, and penalties. In the hands of lawyers, our work must overcome different challenges. Even if the paradigms of the operational health physicist, the scientist, and the regulator match, the odds against the lawyers paradigms also matching are astronomical. The differing paradigms are illustrated by example questions and answers. It is important for educators, trainers, and health physicists to recognize and separate the score-keeping, practice, science, and legal issues in health physics

Eucalyptus globulus extract protects against UVB-induced photoaging by enhancing collagen synthesis via regulation of TGF-β/Smad signals and attenuation of AP-1.

Science.gov (United States)

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.

miR-664 negatively regulates PLP2 and promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Zhu, Hong; Miao, Mei-hua; Ji, Xue-qiang; Xue, Jun; Shao, Xue-jun, E-mail: xuejunshao@hotmail.com

2015-04-03

MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in leukaemia, particularly T-cell acute lymphoblastic leukaemia (T-ALL), has remained elusive. Here, we identified miR-664 and its predicted target gene PLP2 were differentially expressed in T-ALL using bioinformatics methods. In T-ALL cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-664, while miR-664 inhibitor could significantly inhibited the proliferation. Moreover, migration and invasion assay showed that overexpression of miR-664 could significantly promoted the migration and invasion of T-ALL cells, whereas miR-664 inhibitor could reduce cell migration and invasion. luciferase assays confirmed that miR-664 directly bound to the 3'untranslated region of PLP2, and western blotting showed that miR-664 suppressed the expression of PLP2 at the protein levels. This study indicated that miR-664 negatively regulates PLP2 and promotes proliferation and invasion of T-ALL cell lines. Thus, miR-664 may represent a potential therapeutic target for T-ALL intervention. - Highlights: • miR-664 mimics promote the proliferation and invasion of T-ALL cells. • miR-664 inhibitors inhibit the proliferation and invasion of T-ALL cells. • miR-664 targets 3′ UTR of PLP2 in T-ALL cells. • miR-664 negatively regulates PLP2 in T-ALL cells.

5th December 1990 - Royal Order amending the provisions of the General Regulations for protection at work, concerning the protection of workers against the hazards of ionizing radiation

International Nuclear Information System (INIS)

1990-01-01

This Royal Order amending the 1946 General Regulations for the protection of workers against the hazards of ionizing radiation implements on a national level the European Community Directives No. 80/836 Euratom of 15 July 1980 laying down basic safety standards for the health protection of the general public and workers against the hazards of ionizing radiations and No. 84/466 Euratom of 3 September 1984 laying down basic measures for the radiation protection of persons undergoing medical examination or treatment [fr

SIRT1 Functions as an Important Regulator of Estrogen-Mediated Cardiomyocyte Protection in Angiotensin II-Induced Heart Hypertrophy

Directory of Open Access Journals (Sweden)

Tao Shen

2014-01-01

Full Text Available Background. Sirtuin 1 (SIRT1 is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII- induced cardiac hypertrophy and injury in vivo and in vitro. Methods. We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs to investigate the function of SIRT1. Results. SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1’s protective effect. Conclusions. These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury.

Orphan nuclear receptor Nur77 is a novel negative regulator of endothelin-1 expression in vascular endothelial cells.

Science.gov (United States)

Qin, Qing; Chen, Ming; Yi, Bing; You, Xiaohua; Yang, Ping; Sun, Jianxin

2014-12-01

Endothelin-1 (ET-1) produced by vascular endothelial cells plays essential roles in the regulation of vascular tone and development of cardiovascular diseases. The objective of this study is to identify novel regulators implicated in the regulation of ET-1 expression in vascular endothelial cells (ECs). By using quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), we show that either ectopic expression of orphan nuclear receptor Nur77 or pharmacological activation of Nur77 by 6-mercaptopurine (6-MP) substantially inhibits ET-1 expression in human umbilical vein endothelial cells (HUVECs), under both basal and thrombin-stimulated conditions. Furthermore, thrombin-stimulated ET expression is significantly augmented in both Nur77 knockdown ECs and aort from Nur77 knockout mice, suggesting that Nur77 is a negative regulator of ET-1 expression. Inhibition of ET-1 expression by Nur77 occurs at gene transcriptional levels, since Nur77 potently inhibits ET-1 promoter activity, without affecting ET-1 mRNA stability. As shown in electrophoretic mobility shift assay (EMSA), Nur77 overexpression markedly inhibits both basal and thrombin-stimulated transcriptional activity of AP-1. Mechanistically, we demonstrate that Nur77 specially interacts with c-Jun and inhibits AP-1 dependent c-Jun promoter activity, which leads to a decreased expression of c-Jun, a critical component involved in both AP-1 transcriptional activity and ET-1 expression in ECs. These findings demonstrate that Nur77 is a novel negative regulator of ET-1 expression in vascular ECs through an inhibitory interaction with the c-Jun/AP-1 pathway. Activation of Nur77 may represent a useful therapeutic strategy for preventing certain cardiovascular diseases, such as atherosclerosis and pulmonary artery hypertension. Copyright © 2014 Elsevier Ltd. All rights reserved.

Functional analysis of Arabidopsis immune-related MAPKs uncovers a role for MPK3 as negative regulator of inducible defences

KAUST Repository

Frei dit Frey, Nicolas

2014-06-30

Background Mitogen-activated protein kinases (MAPKs) are key regulators of immune responses in animals and plants. In Arabidopsis, perception of microbe-associated molecular patterns (MAMPs) activates the MAPKs MPK3, MPK4 and MPK6. Increasing information depicts the molecular events activated by MAMPs in plants, but the specific and cooperative contributions of the MAPKs in these signalling events are largely unclear. Results In this work, we analyse the behaviour of MPK3, MPK4 and MPK6 mutants in early and late immune responses triggered by the MAMP flg22 from bacterial flagellin. A genome-wide transcriptome analysis reveals that 36% of the flg22-upregulated genes and 68% of the flg22-downregulated genes are affected in at least one MAPK mutant. So far MPK4 was considered as a negative regulator of immunity, whereas MPK3 and MPK6 were believed to play partially redundant positive functions in defence. Our work reveals that MPK4 is required for the regulation of approximately 50% of flg22-induced genes and we identify a negative role for MPK3 in regulating defence gene expression, flg22-induced salicylic acid accumulation and disease resistance to Pseudomonas syringae. Among the MAPK-dependent genes, 27% of flg22-upregulated genes and 76% of flg22-downregulated genes require two or three MAPKs for their regulation. The flg22-induced MAPK activities are differentially regulated in MPK3 and MPK6 mutants, both in amplitude and duration, revealing a highly interdependent network. Conclusions These data reveal a new set of distinct functions for MPK3, MPK4 and MPK6 and indicate that the plant immune signalling network is choreographed through the interplay of these three interwoven MAPK pathways.

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

International Nuclear Information System (INIS)

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

1988-01-01

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

The general principles of radiation protection and regulation; Les principes generaux de la radioprotection et la reglementation

Energy Technology Data Exchange (ETDEWEB)

Aurengo, A [Societe Francaise de Radioprotection, 34 - Montpellier (France); Cesarini, J P [Societe Francaise de Radioprotection, Section Rayonnements non ionisants, 75 - Paris (France); Lecomte, J F; Barbier, G; Crescini, D; Biau, A [CEA Fontenay aux Roses, Institut de Radioprotection et de Surete Nucleaire IRSN, 92 (France); Blain, A [FRAMATOME, Dir. Combustible Nucleaire, Dept. Radioprotection Securite, 69 - Lyon (France); Bailloeuil, C; Gonin, M [Electricite de France, EDF-SCAST, 75 - Paris (France); Bergot, D [Ministere des Affaires Sociales, du Travail et de la Solidarite, Dir. des Relations du Travail, 75 - Paris (France)

2003-07-01

Seven articles constitute this chapter about the radiation protection and the regulation. Radiological risk, reduction of public exposure to ultraviolet radiations, regulation for the radon, evolution of the French legislation against the dangers of ionizing radiations, the medical follow up after the professional life, the information system to reproduce the dosimetric data of workers, proposition of a scale to classify the radiations incidents in function of their seriousness. (N.C.)

The Relations Between Maternal Prenatal Anxiety or Stress and Child's Early Negative Reactivity or Self-Regulation: A Systematic Review.

Science.gov (United States)

Korja, Riikka; Nolvi, Saara; Grant, Kerry Ann; McMahon, Cathy

2017-12-01

In the present review, we examine the association between maternal prenatal stress or anxiety and children's early negative reactivity or self-regulation. The review includes 32 studies that focus on pregnancy-related anxiety, state or trait anxiety, perceived stress, and stressful life events in relation to child's crying, temperament, or behavior during the first 2 years of life. We searched four electronic databases and 32 studies were selected based on the inclusion criteria. Twenty-three studies found an association between maternal prenatal anxiety or stress and a child's negative reactivity or self-regulation, and typically the effect sizes varied from low to moderate. The association was found regardless of the form of prenatal stress or anxiety and the trimester in which the prenatal stress or anxiety was measured. In conclusion, several forms of prenatal anxiety and stress may increase the risk of emotional and self-regulatory difficulties during the first 2 years of life.

Improved protection system for phase faults on marine vessels based on ratio between negative sequence and positive sequence of the fault current

DEFF Research Database (Denmark)

Ciontea, Catalin-Iosif; Hong, Qiteng; Booth, Campbell

2018-01-01

algorithm is implemented in a programmable digital relay embedded in a hardware-in-the-loop (HIL) test set-up that emulates a typical maritime feeder using a real-time digital simulator. The HIL set-up allows testing of the new protection method under a wide range of faults and network conditions......This study presents a new method to protect the radial feeders on marine vessels. The proposed protection method is effective against phase–phase (PP) faults and is based on evaluation of the ratio between the negative sequence and positive sequence of the fault currents. It is shown...... that the magnitude of the introduced ratio increases significantly during the PP fault, hence indicating the fault presence in an electric network. Here, the theoretical background of the new method of protection is firstly discussed, based on which the new protection algorithm is described afterwards. The proposed...

Regulation of non-relevant metabolites of plant protection products in drinking and groundwater in the EU: Current status and way forward.

Science.gov (United States)

Laabs, V; Leake, C; Botham, P; Melching-Kollmuß, S

2015-10-01

Non-relevant metabolites are defined in the EU regulation for plant protection product authorization and a detailed definition of non-relevant metabolites is given in an EU Commission DG Sanco (now DG SANTE - Health and Food Safety) guidance document. However, in water legislation at EU and member state level non-relevant metabolites of pesticides are either not specifically regulated or diverse threshold values are applied. Based on their inherent properties, non-relevant metabolites should be regulated based on substance-specific and toxicity-based limit values in drinking and groundwater like other anthropogenic chemicals. Yet, if a general limit value for non-relevant metabolites in drinking and groundwater is favored, an application of a Threshold of Toxicological Concern (TTC) concept for Cramer class III compounds leads to a threshold value of 4.5 μg L(-1). This general value is exemplarily shown to be protective for non-relevant metabolites, based on individual drinking water limit values derived for a set of 56 non-relevant metabolites. A consistent definition of non-relevant metabolites of plant protection products, as well as their uniform regulation in drinking and groundwater in the EU, is important to achieve legal clarity for all stakeholders and to establish planning security for development of plant protection products for the European market. Copyright © 2015 Elsevier Inc. All rights reserved.

The Putative PAX8/PPARγ Fusion Oncoprotein Exhibits Partial Tumor Suppressor Activity through Up-Regulation of Micro-RNA-122 and Dominant-Negative PPARγ Activity.

Science.gov (United States)

Reddi, Honey V; Madde, Pranathi; Milosevic, Dragana; Hackbarth, Jennifer S; Algeciras-Schimnich, Alicia; McIver, Bryan; Grebe, Stefan K G; Eberhardt, Norman L

2011-01-01

In vitro studies have demonstrated that the PAX8/PPARγ fusion protein (PPFP), which occurs frequently in follicular thyroid carcinomas (FTC), exhibits oncogenic activity. However, paradoxically, a meta-analysis of extant tumor outcome studies indicates that 68% of FTC-expressing PPFP are minimally invasive compared to only 32% of those lacking PPFP (χ(2) = 6.86, P = 0.008), suggesting that PPFP favorably impacts FTC outcomes. In studies designed to distinguish benign thyroid neoplasms from thyroid carcinomas, the previously identified tumor suppressor miR-122, a major liver micro-RNA (miR) that is decreased in hepatocellular carcinoma, was increased 8.9-fold (P negative PPARγ mutant in WRO cells was less effective than PPFP at inhibiting xenograft tumor progression (1.8-fold [P negative PPARγ activity. Up-regulation of miR-122 negatively regulates ADAM-17, a known downstream target, in thyroid cells, suggesting an antiangiogenic mechanism in thyroid carcinoma. This latter inference is directly supported by reduced CD-31 expression in WRO xenografts expressing PPFP, miR-122, and DN-PPARγ. We conclude that, in addition to its apparent oncogenic potential in vitro, PPFP exhibits paradoxical tumor suppressor activity in vivo, mediated by multiple mechanisms including up-regulation of miR-122 and dominant-negative inhibition of PPARγ activity.

The Swedish Radiation Protection Institute's regulations concerning the final management of spent nuclear fuel and nuclear waste - with background and comments

International Nuclear Information System (INIS)

2000-11-01

This report presents and comments on the Swedish Radiation Protection Institute's Regulations concerning the Protection of Human Health and the Environment in connection with the Final Management of Spent Nuclear Fuel or Nuclear Waste, SSI FS 1998: 1

Parental Emotion Coaching and Child Emotion Regulation as Protective Factors for Children with Oppositional Defiant Disorder

Science.gov (United States)

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…

Physical protection of nuclear materials: Experience in regulation, implementation and operations. Proceedings of a conference

International Nuclear Information System (INIS)

1998-01-01

The conference was held at IAEA Headquarters in Vienna from 10 to 14 November 1997. It was attended by 162 registered participants from 42 countries and eight international organizations. The 58 papers presented dealt with the experience of regulators, designers and facility operators, including response forces, in meeting the demands and requirements in this changing area of physical protection of nuclear materials and facilities. Individual abstracts were prepared for each of the papers. Topics covered include contemporary and emerging issues, experience in regulation, implementation at facilities, program assessment and cooperation, hardware and software, illicit trafficking in nuclear materials, and transportation

Ethylene response factor AtERF72 negatively regulates Arabidopsis thaliana response to iron deficiency.

Science.gov (United States)

Liu, Wei; Li, Qiwei; Wang, Yi; Wu, Ting; Yang, Yafei; Zhang, Xinzhong; Han, Zhenhai; Xu, Xuefeng

2017-09-23

Ethylene regulates the plant's response to stress caused by iron (Fe) deficiency. However, specific roles of ERF proteins in response to Fe deficiency remain poorly understood. Here, we investigated the role of ERF72 in response to iron deficiency in Arabidopsis thaliana. In this study, the levels of the ethylene response factor AtERF72 increased in leaves and roots induced under the iron deficient conditions. erf72 mutant plants showed increased growth compared to wild type (WT) when grown in iron deficient medium for 5 d. erf72 mutants had increased root H + velocity and the ferric reductase activity, and increase in the expression of the iron deficiency response genes iron-regulated transporter 1 (IRT1) and H + -ATPase (HA2) levels in iron deficient conditions. Compared to WT plants, erf72 mutants retained healthy chloroplast structure with significantly higher Fe and Mg content, and decreased chlorophyll degradation gene pheophorbide a oxygenase (PAO) and chlorophyllase (CLH1) expression when grown in iron deficient media. Yeast one-hybrid analysis showed that ERF72 could directly bind to the promoter regions of iron deficiency responses genes IRT1, HA2 and CLH1. Based on our results, we suggest that ethylene released from plants under iron deficiency stress can activate the expression of ERF72, which responds to iron deficiency in the negative regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Sec. 46 of the radiation protection ordinance - waiting for implementing regulations

International Nuclear Information System (INIS)

Maushart, R.

1977-01-01

There is much uncertainty among the users of radioactive substances in research and medicine about the practical consequences stemming from Sec. 46 of the new Radiation Protection Ordinance with respect to releases of radionuclides with the air and water. On the one hand, the 30 mrem concept has drastically curbed permissible release concentrations. In addition, balancing for each specific nuclide has become compulsory. Both conditions would demand a revision and extension of present measuring techniques. However, the responsible supervisory authorities are unable to issue any rules or regulations as long as there are no uniform standards. The consequence is a complete lack of knowledge, both on the part of users and the supplying industries, about the future expenditure necessary for liquid and gaseous effluent control and the technical performance criteria to be met by radiation measuring equipment. It is to be hoped that these implementing regulations, which are so urgently needed, will soon be published so as to allow users to engage in meaningful and binding planning again, both technically and financially. (orig.) [de

Nitrate Protects Cucumber Plants Against Fusarium oxysporum by Regulating Citrate Exudation.

Science.gov (United States)

Wang, Min; Sun, Yuming; Gu, Zechen; Wang, Ruirui; Sun, Guomei; Zhu, Chen; Guo, Shiwei; Shen, Qirong

2016-09-01

Fusarium wilt causes severe yield losses in cash crops. Nitrogen plays a critical role in the management of plant disease; however, the regulating mechanism is poorly understood. Using biochemical, physiological, bioinformatic and transcriptome approaches, we analyzed how nitrogen forms regulate the interactions between cucumber plants and Fusarium oxysporum f. sp. cucumerinum (FOC). Nitrate significantly suppressed Fusarium wilt compared with ammonium in both pot and hydroponic experiments. Fewer FOC colonized the roots and stems under nitrate compared with ammonium supply. Cucumber grown with nitrate accumulated less fusaric acid (FA) after FOC infection and exhibited increased tolerance to chemical FA by decreasing FA absorption and transportation in shoots. A lower citrate concentration was observed in nitrate-grown cucumbers, which was associated with lower MATE (multidrug and toxin compound extrusion) family gene and citrate synthase (CS) gene expression, as well as lower CS activity. Citrate enhanced FOC spore germination and infection, and increased disease incidence and the FOC population in ammonium-treated plants. Our study provides evidence that nitrate protects cucumber plants against F. oxysporum by decreasing root citrate exudation and FOC infection. Citrate exudation is essential for regulating disease development of Fusarium wilt in cucumber plants. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The national radiation protection infrastructure

International Nuclear Information System (INIS)

Mastauskas, A.

1999-01-01

The state system of radiation protection is still being created after Lithuania regained its independancy and in connection with recommendations laid in the ICRP-60 publication and requirements of legislation of European Community. A new regulation institutions was established and a number of laws and regulations related to radiation protection was prepared. The Radiation Protection Centre of Ministry of Health is the regulatory authority responsible for radiation protection of public and of workers using sources of ionizing radiation in Lithuania. A new Radiation Protection Law, Nuclear Energy Law, Radioactive Waste Management Law and different regulations was approved. Preparation of legislation, creation of state system of radiation protection and its upgrading allow to presume that the necessary level of radiation protection is to be achieved. (au)

Radiation protection and the safe use of X-ray equipment: Laws, regulations and responsibilities

Directory of Open Access Journals (Sweden)

Charles Petrus Herbst

2012-06-01

Full Text Available Lately, South Africa’s regulatory framework for electromagnetic medical devices has come under considerable pressure. In this article the legislative framework and regulatory infrastructure are scrutinized, by looking at how the legislature has given form to protective measures against ionizing radiation. Although the Hazardous Substances Act provides for effective protection against radiation, poor administration led to insufficient staffing levels, uncertainty about Regulations and licensing conditions and therefore undermines a sound radiation protection infrastructure. The legal basis of enforcing licensing conditions through a website without proper consultation with interested and affected parties is questionable and ineffective in controlling radiation levels. Effective and legal radiation control is possible by activating the National Advisory Committee on Electronic Products provided for in Regulation R326 published in 1979, but never implemented. The possible impact of annual quality assurance tests currently enforced through licensing conditions on the radiation dose of the population is not cost effective as new training and accreditation structures had to be created. The fact that generally more than 80% of overexposures are caused by human error is a clear indication that training of the daily users of X-ray equipment should be emphasized and not the training and accreditation of the technicians responsible for a single quality assurance test per year. Constructive engagement with the professional bodies involved in the medical use of X-rays through a National Advisory Committee on Electronic Products may be a cost effective solution for lowering radiation dose to the population.

Survey of International Rules and Practices Regarding Delineation of and Access to Regulated Areas for Radiation Protection - Final report

International Nuclear Information System (INIS)

Schieber, C.; Crouail, P.; Beltrami, L.-A.; Reaud, C.; Lehtinen, Maaret; Stritt, Nicolas; Thomas, Gareth

2013-06-01

European requirements for radiological protection, especially work on transposing the new EURATOM Directive on the basic radiological protection standards, are currently being revised. The Direction generale du travail (DGT - General Directorate of Labour) and the Autorite de Surete Nucleaire (ASN - Nuclear Safety Authority) therefore commissioned the Radiological Protection Standing Groups of experts (GPRAD and GPMED)1 to engage in a forward-looking debate on the delimitation of and access to regulated areas, within an ad hoc working group (called hereafter 'Classification of Area WG'). To fuel its debates, the 'Classification of Area WG' sought elements on international regulations and practices focusing on problem exposure situations in various areas of activity (nuclear, industrial, research, medical, transport and natural boosted). CEPN was entrusted with this study. This report presents a summary of rules applicable in seven countries in terms of delimitation of and access to regulated radiological protection areas. The countries are: Belgium, Spain, United States, Finland, United Kingdom, Sweden and Switzerland. Detailed sheets for each country can be found in the Annex. Based on these summaries, three countries have been selected to apply their rules and practices in force to a dozen or so particular cases put together by the 'Classification of Area WG' that are representative of exposure situations. The three countries are Finland, United Kingdom and Switzerland. The case studies applied to each country are presented in the second part of this report

PTP1B is a negative regulator of interleukin 4–induced STAT6 signaling

Science.gov (United States)

Lu, Xiaoqing; Malumbres, Raquel; Shields, Benjamin; Jiang, Xiaoyu; Sarosiek, Kristopher A.; Natkunam, Yasodha

2008-01-01

Protein tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed enzyme shown to negatively regulate multiple tyrosine phosphorylation-dependent signaling pathways. PTP1B can modulate cytokine signaling pathways by dephosphorylating JAK2, TYK2, and STAT5a/b. Herein, we report that phosphorylated STAT6 may serve as a cytoplasmic substrate for PTP1B. Overexpression of PTP1B led to STAT6 dephosphorylation and the suppression of STAT6 transcriptional activity, whereas PTP1B knockdown or deficiency augmented IL-4–induced STAT6 signaling. Pretreatment of these cells with the PTK inhibitor staurosporine led to sustained STAT6 phosphorylation consistent with STAT6 serving as a direct substrate of PTP1B. Furthermore, PTP1B-D181A “substrate-trapping” mutants formed stable complexes with phosphorylated STAT6 in a cellular context and endogenous PTP1B and STAT6 interacted in an interleukin 4 (IL-4)–inducible manner. We delineate a new negative regulatory loop of IL-4–JAK-STAT6 signaling. We demonstrate that IL-4 induces PTP1B mRNA expression in a phosphatidylinositol 3-kinase–dependent manner and enhances PTP1B protein stability to suppress IL-4–induced STAT6 signaling. Finally, we show that PTP1B expression may be preferentially elevated in activated B cell–like diffuse large B-cell lymphomas. These observations identify a novel regulatory loop for the regulation of IL-4–induced STAT6 signaling that may have important implications in both neoplastic and inflammatory processes. PMID:18716132

76 FR 27897 - Security and Safety Zone Regulations, Large Passenger Vessel Protection, Captain of the Port...

Science.gov (United States)

2011-05-13

... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2011-0342] Security and Safety Zone Regulations, Large Passenger Vessel Protection, Captain of the Port Columbia River... will enforce the security and safety zone in 33 CFR 165.1318 for large passenger vessels operating in...

Regulations concerning radiation protection and survey; Donnees de la surveillance et regles qui en resultent en matiere de protection contre les rayonnements

Energy Technology Data Exchange (ETDEWEB)

Duhamel,; Lavie,; Fitoussi, [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1958-07-01

The many and always increasing applications of Atomic Energy for peaceful uses set many safety and security problems relatively to the workers, populations, and locating of the sites in general. A comparative study of the radiation hazards to which the people working in the 'Commissariat a l'energie atomique' installations were exposed during 1957 and the results obtained concerning individual and collective safety and security were extremely satisfactory owing to a continuous control and supervision. 2. However a few contamination and irradiation incidents - exposed subsequently as well as the way they were dealt with - show the necessity of a circumstantial regulation inside of an atomic center to establish the responsibility of the service in charge of the control of the radiation and the responsibility of the services using radioactive products with regard to contamination by radioactive materials. 3. Abstract of the different practical safety and security regulations concerning holding, manipulation, transport and stocking of radioactive materials. Pursuant to the recommendations of the International Commission on Radiologic Protection, the radioelements are classified according to the danger that can occur from them in comparison with the Pu with regard to: - radioactive noxiousness; specific activity per unit of mass; contamination hazards. 4. The service in charge of radiation protection plays the important part of a technical adviser for the construction of specialized laboratories and sees to the keeping of protection regulations. 5. Data essential to radiation protection are given to the people using radioactive materials; particularly: - a table of the radioisotopes and the hazards occurring from them; - radiation hazards regarding {gamma} ray emitted by irradiated Pu; - radiation hazards regarding {gamma} ray emitted by irradiated Th. 6. As the hazards occasioned by irradiated uranium have already been studied, the case of a low and total irradiation

Leukocyte-associated immunoglobulin-like receptor-1 is expressed on human megakaryocytes and negatively regulates the maturation of primary megakaryocytic progenitors and cell line

International Nuclear Information System (INIS)

Xue, Jiangnan; Zhang, Xiaoshu; Zhao, Haiya; Fu, Qiang; Cao, Yanning; Wang, Yuesi; Feng, Xiaoying; Fu, Aili

2011-01-01

Research highlights: → LAIR-1 is expressed on human megakaryocytes from an early stage. → Up-regulation of LAIR-1 negatively regulates megakaryocytic differentiation of cell line. → LAIR-1 negatively regulates the differentiation of primary megakaryocytic progenitors. -- Abstract: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory collagen receptor which belongs to the immunoglobulin (Ig) superfamily. Although the inhibitory function of LAIR-1 has been extensively described in multiple leukocytes, its role in megakaryocyte (MK) has not been explored so far. Here, we show that LAIR-1 is expressed on human bone marrow CD34 + CD41a + and CD41a + CD42b + cells. LAIR-1 is also detectable in a fraction of human cord blood CD34 + cell-derived MK that has morphological characteristics of immature MK. In megakaryoblastic cell line Dami, the membrane protein expression of LAIR-1 is up-regulated significantly when cells are treated with phorbol ester phorbol 12-myristate 13-acetate (PMA). Furthermore, cross-linking of LAIR-1 in Dami cells with its natural ligand or anti-LAIR-1 antibody leads to the inhibition of cell proliferation and PMA-promoted differentiation when examined by the MK lineage-specific markers (CD41a and CD42b) and polyploidization. In addition, we also observed that cross-linking of LAIR-1 results in decreased MK generation from primary human CD34 + cells cultured in a cytokines cocktail that contains TPO. These results suggest that LAIR-1 is a likely candidate for an early marker of MK differentiation, and provide initial evidence indicating that LAIR-1 serves as a negative regulator of megakaryocytopoiesis.

A road paved with safe intentions: Increasing intentions to use alcohol protective behavioral strategies via Deviance Regulation Theory.

Science.gov (United States)

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).

Alcohol Use, Hostile Sexism, and Religious Self-Regulation: Investigating Risk and Protective Factors of IPV Perpetration.

Science.gov (United States)

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.

Overexpression of Cdk5 or non-phosphorylatable retinoblastoma protein protects septal neurons from oxygen-glucose deprivation.

Science.gov (United States)

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.

Regulation of radiation protective agents on cell damage induced by reactive oxygen species

Energy Technology Data Exchange (ETDEWEB)

Kim, Jeong Hee; Lee, Si Eun; Ju, Eun Mi; Gao, Eu Feng [Kyung Hee University, Seoul (Korea)

2002-04-01

In this study, we developed candidates of new radio-protective agents and elucidated the regulation mechanism of these candidates on cell damage induced by reactive oxygen species. The methanol extracts and ethylacetate fractions of NP-1, NP-5, NP-7, NP-11, NP-12 and NP-14 showed higher radical scavenging activity. The extracts of NP-7, NP-12 and NP-14 showed strong protective effect against oxidative damage induced by UV and H{sub 2}O{sub 2}. The most of samples enhanced SOD, CAT and GPX activity in V79-4 cells. The protective effect of samples on H{sub 2}O{sub 2}-induced apoptosis was observed with microscope and flow cytometer. Cells exposed to H{sub 2}O{sub 2} exhibit distinct morphological features of programmed cell death, such as nuclear fragmentation and increase in the percentage of cells with a sub-G1 DNA content. However, cells which was pretreated with samples significantly reduced the characteristics of apoptotic cells. Their morphological observation and DNA profiles were similar to those of the control cells. NP-14 which had excellent antioxidant activity restored G2/M arrest induced by oxidative stress. These data suggested that natural medicinal plants protected H{sub 2}O{sub 2}-induced apoptosis. 42 refs., 29 figs., 11 tabs. (Author)

Performance goals in conflictual social interactions: towards the distinction between two modes of relational conflict regulation.

Science.gov (United States)

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.

NK Cell-Mediated Regulation of Protective Memory Responses against Intracellular Ehrlichial Pathogens.

Directory of Open Access Journals (Sweden)

Samar Habib

Full Text Available Ehrlichiae are gram-negative obligate intracellular bacteria that cause potentially fatal human monocytic ehrlichiosis. We previously showed that natural killer (NK cells play a critical role in host defense against Ehrlichia during primary infection. However, the contribution of NK cells to the memory response against Ehrlichia remains elusive. Primary infection of C57BL/6 mice with Ehrlichia muris provides long-term protection against a second challenge with the highly virulent Ixodes ovatus Ehrlichia (IOE, which ordinarily causes fatal disease in naïve mice. Here, we show that the depletion of NK cells in E. muris-primed mice abrogates the protective memory response against IOE. Approximately, 80% of NK cell-depleted E. muris-primed mice succumbed to lethal IOE infection on days 8-10 after IOE infection, similar to naïve mice infected with the same dose of IOE. The lack of a recall response in NK cell-depleted mice correlated with an increased bacterial burden, extensive liver injury, decreased frequency of Ehrlichia-specific IFN-γ-producing memory CD4+ and CD8+ T-cells, and a low titer of Ehrlichia-specific antibodies. Intraperitoneal infection of mice with E. muris resulted in the production of IL-15, IL-12, and IFN-γ as well as an expansion of activated NKG2D+ NK cells. The adoptive transfer of purified E. muris-primed hepatic and splenic NK cells into Rag2-/-Il2rg-/- recipient mice provided protective immunity against challenge with E. muris. Together, these data suggest that E. muris-induced memory-like NK cells, which contribute to the protective, recall response against Ehrlichia.

Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment

Science.gov (United States)

Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Fahey, Frederic; Daley, George Q.

2009-01-01

Osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC) in mammalian bone marrow (BM) 1,2,3 . Adult BM also contains adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. Fatty infiltration of hematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia 4. To explore whether adipocytes influence hematopoiesis or simply fill marrow space, we compared the hematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. By flow cytometry, colony forming activity, and competitive repopulation assay, HSCs and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 “fatless” mice, which are genetically incapable of forming adipocytes8, and in mice treated with the PPARγ inhibitor Bisphenol-A-DiGlycidyl-Ether (BADGE), which inhibits adipogenesis9, post-irradiation marrow engraftment is accelerated relative to wild type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone marrow microenvironment, and suggest that antagonizingmarrow adipogenesis may enhance hematopoietic recovery in clinical bone marrow transplantation. PMID:19516257

Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive Chlamydia trachomatis Biovars

Directory of Open Access Journals (Sweden)

Michael John Patton

2018-01-01

Full Text Available Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes blinding trachoma and sexually transmitted disease. C. trachomatis isolates are classified into 2 biovars—lymphogranuloma venereum (LGV and trachoma—which are distinguished biologically by their natural host cell infection tropism. LGV biovars infect macrophages and are invasive, whereas trachoma biovars infect oculo-urogenital epithelial cells and are noninvasive. The C. trachomatis plasmid is an important virulence factor in the pathogenesis of these infections. Central to its pathogenic role is the transcriptional regulatory function of the plasmid protein Pgp4, which regulates the expression of plasmid and chromosomal virulence genes. As many gene regulatory functions are post-transcriptional, we employed a comparative proteomic study of cells infected with plasmid-cured C. trachomatis serovars A and D (trachoma biovar, a L2 serovar (LGV biovar, and the L2 serovar transformed with a plasmid containing a nonsense mutation in pgp4 to more completely elucidate the effects of the plasmid on chlamydial infection biology. Our results show that the Pgp4-dependent elevations in the levels of Pgp3 and a conserved core set of chromosomally encoded proteins are remarkably similar for serovars within both C. trachomatis biovars. Conversely, we found a plasmid-dependent, Pgp4-independent, negative regulation in the expression of the chlamydial protease-like activity factor (CPAF for the L2 serovar but not the A and D serovars. The molecular mechanism of plasmid-dependent negative regulation of CPAF expression in the LGV serovar is not understood but is likely important to understanding its macrophage infection tropism and invasive infection nature.

Mycobacterium tuberculosis maltosyltransferase GlgE, a genetically validated antituberculosis target, is negatively regulated by Ser/Thr phosphorylation.

Science.gov (United States)

Leiba, Jade; Syson, Karl; Baronian, Grégory; Zanella-Cléon, Isabelle; Kalscheuer, Rainer; Kremer, Laurent; Bornemann, Stephen; Molle, Virginie

2013-06-07

GlgE is a maltosyltransferase involved in the biosynthesis of α-glucans that has been genetically validated as a potential therapeutic target against Mycobacterium tuberculosis. Despite also making α-glucan, the GlgC/GlgA glycogen pathway is distinct and allosterically regulated. We have used a combination of genetics and biochemistry to establish how the GlgE pathway is regulated. M. tuberculosis GlgE was phosphorylated specifically by the Ser/Thr protein kinase PknB in vitro on one serine and six threonine residues. Furthermore, GlgE was phosphorylated in vivo when expressed in Mycobacterium bovis bacillus Calmette-Guérin (BCG) but not when all seven phosphorylation sites were replaced by Ala residues. The GlgE orthologues from Mycobacterium smegmatis and Streptomyces coelicolor were phosphorylated by the corresponding PknB orthologues in vitro, implying that the phosphorylation of GlgE is widespread among actinomycetes. PknB-dependent phosphorylation of GlgE led to a 2 orders of magnitude reduction in catalytic efficiency in vitro. The activities of phosphoablative and phosphomimetic GlgE derivatives, where each phosphorylation site was substituted with either Ala or Asp residues, respectively, correlated with negative phosphoregulation. Complementation studies of a M. smegmatis glgE mutant strain with these GlgE derivatives, together with both classical and chemical forward genetics, were consistent with flux through the GlgE pathway being correlated with GlgE activity. We conclude that the GlgE pathway appears to be negatively regulated in actinomycetes through the phosphorylation of GlgE by PknB, a mechanism distinct from that known in the classical glycogen pathway. Thus, these findings open new opportunities to target the GlgE pathway therapeutically.

Neural activity to a partner's facial expression predicts self-regulation after conflict

Science.gov (United States)

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

Neural activity to a partner's facial expression predicts self-regulation after conflict.

Science.gov (United States)

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.

Measurement and assessment of doses from external radiations required for revised radiation protection regulations

Energy Technology Data Exchange (ETDEWEB)

Tsujimura, Norio; Kojima, Noboru; Hayashi, Naomi [Japan Nuclear Cycle Development Inst., Tokai, Ibaraki (Japan)

2001-06-01

Radiation protection regulations based on the 1990 recommendations of ICRP have been revised and will take effect from Apr., 2001. The major changes concerning on the measurement and assessment of doses from external radiations are as follows. (1) Personal dose equivalent and ambient dose equivalent stated in ICRP Publication 74 are introduced as quantities to be measured with personal dosimeters and survey instruments, respectively. (2) For multiple dosimetry for workers, the compartment weighting factors used for a realistic assessment of effective dose are markedly changed. In advance of the introduction of the new radiation protection regulations, the impacts on workplace and personal monitoring for external radiations by these revisions were investigated. The following results were obtained. (1) A new ambient dose equivalent to neutrons is higher with a factor of 1.2 than the old one for moderated fission neutron spectra. Therefore, neutron dose equivalent monitors for workplace monitoring at MOX fuel for facilities should be recalibrated for measurement of the new ambient dose equivalent. (2) Annual effective doses of workers were estimated by applying new calibration factors to readings of personal dosimeters, worn by workers. Differences between effective doses and effective dose equivalents are small for workers engaged in the fabrication process of MOX fuel. (author)

Measurement and assessment of doses from external radiations required for revised radiation protection regulations

International Nuclear Information System (INIS)

Tsujimura, Norio; Kojima, Noboru; Hayashi, Naomi

2001-01-01

Radiation protection regulations based on the 1990 recommendations of ICRP have been revised and will take effect from Apr., 2001. The major changes concerning on the measurement and assessment of doses from external radiations are as follows. (1) Personal dose equivalent and ambient dose equivalent stated in ICRP Publication 74 are introduced as quantities to be measured with personal dosimeters and survey instruments, respectively. (2) For multiple dosimetry for workers, the compartment weighting factors used for a realistic assessment of effective dose are markedly changed. In advance of the introduction of the new radiation protection regulations, the impacts on workplace and personal monitoring for external radiations by these revisions were investigated. The following results were obtained. (1) A new ambient dose equivalent to neutrons is higher with a factor of 1.2 than the old one for moderated fission neutron spectra. Therefore, neutron dose equivalent monitors for workplace monitoring at MOX fuel for facilities should be recalibrated for measurement of the new ambient dose equivalent. (2) Annual effective doses of workers were estimated by applying new calibration factors to readings of personal dosimeters, worn by workers. Differences between effective doses and effective dose equivalents are small for workers engaged in the fabrication process of MOX fuel. (author)

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

Science.gov (United States)

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

2015-06-01

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

Regulation of the State Office of Nuclear Safety No. 307/2002 of 13 June April 2002 on radiation protection

International Nuclear Information System (INIS)

2002-01-01

The Regulation is a basic Czech document governing any activity associated with ionizing radiations. It comprises the following sections: (1) Introductory and general provisions (Classification of ionizing radiation sources; Categorization of workplaces performing radiation activities; Exposure optimization and limits) (2) Radiation activities (Conditions of a safe operation of workplaces performing radiation activities; Ionizing radiation source handling; Radioactive waste handling; Introduction of radionuclides into the environment; Other radiation activities; Details of conditions of medical examination; Monitoring, measuring, evaluating, verifying and recording radiation protection-related quantities, parameters and facts; Ionizing radiation source accountancy and recording of other radiation protection-related facts) (3) Working activities associated with enhanced exposure from natural sources; (4) Interventions to avert or reduce exposure (Interventions to reduce exposure to natural ionizing radiation sources; Interventions during radiation emergency situations; Interventions during persisting exposure). The document consists of 45 pages of text and 134 pages of annexes with tables and forms. This Regulation supersedes Regulation No. 184/1997. (P.A.)

Comparison between the Brazilian regulation of radioprotection and the recommendation of International Commission on Radiological Protection published in 2007; Comparacao entre a norma brasileira de radioprotecao e a recomendacao da International Commission on Radiological Protection publicadas em 2007

Energy Technology Data Exchange (ETDEWEB)

Pereira, Wagner S.; Py Junior, Delcy A.; Dantas, Marcelino V.A.; Oliveira, Sergio Q. de, E-mail: wspereira@inb.gov.b, E-mail: delcy@inb.gov.b, E-mail: marcelino@inb.gov.b [Industrias Nucleares do Brasil (UTM/INB), Pocos de Caldas, MG (Brazil). Unidade de Tratamento de Minerios; Kelecom, Alphonse [Universidade Federal Fluminense (LARARA/UFF), Niteroi, RJ (Brazil). Lab. de Radiobiologia e Radiometria; Mortagua, Valter Jose, E-mail: Valter@inb.gov.b [Industrias Nucleares do Brasil (USIN/INB), SP (Brazil). Usina de Interlagos

2011-10-26

This paper intends to compare the Brasilian basic regulation on radiological protection with the new recommendations of ICRP through existent differences. The main difference between the publication 60 and the publication 103 of the ICRP is the changing of concept of protection based on the process by use of practice and intervention concepts, to the protection based on the exposure situation, through the concepts of planned exposure, emergency and existent situation. For adequacy to the Brazilian regulation it is necessary to change its concept of protection and the values of radiation weighing and tissues, up dating of radiation detriments, besides to make clear the concept of environmental radioprotection

The Radiation Protection Act

International Nuclear Information System (INIS)

Persson, L.

1989-01-01

The new Radiation Protection Act (1988:220) entered into force in Sweden on July 1st, 1988. This book presents the Act as well as certain regulations connected to it. As previously, the main responsibility for public radiation protection will rest with one central radiation protection authority. According to the 1988 Act, the general obligations with regard to radiation protection will place a greater responsibility than in the past on persons carrying out activities involving radiation. Under the act, it is possible to adjust the licensing and supervisory procedures to the level of danger of the radiation source and the need for adequate competence, etc. The Act recognises standardised approval procedures combined with technical regulations for areas where the risks are well known. The Act contains several rules providing for more effective supervision. The supervising authority may in particular decide on the necessary regulations and prohibitions for each individual case. The possibilities of using penal provisions have been extended and a rule on the mandatory execution of orders has been introduced. The Ordinance on Radiation Protection (1988:293) designates the National Institute of Radiation Protection (SSI) as the central authority referred to in the Radiation Protection Act. The book also gives a historic review of radiation protection laws in Sweden, lists regulations issued by SSI and presents explanations of radiation effects and international norms in the area. (author)

The efficiency cost of protective measures in climate policy

International Nuclear Information System (INIS)

Böhringer, Christoph; Garcia-Muros, Xaquin; Cazcarro, Ignacio; Arto, Iñaki

2017-01-01

Despite recent achievements towards a global climate agreement, climate action to reduce greenhouse gas emissions remains quite heterogeneous across countries. Energy-intensive and trade-exposed (EITE) industries in industrialized countries are concerned on stringent domestic emission pricing that puts them at a competitive disadvantage against producers of similar goods in other countries with more lenient emission regulation. This paper focuses on climate policy design in the United States of America (US) and compares the economic implications of four alternative protective measures for US EITE industries: (i) output-based rebates, (ii) exemptions from emission pricing, (iii) energy intensity standards, and (iv) carbon intensity standards. Using a large-scale computable general equilibrium model we quantify how these protective measures affect competitiveness of US EITE industries. We find that protective measures can improve common trade-related competitiveness indicators such as revealed comparative advantage or relative world trade shares but at the same time may lead to a decline in the output value for EITE industries because of negative income effects. The economy-wide cost of emission abatement under protective measures increase as compared to uniform emission pricing stand-alone such that the gains of protective measures for EITE exports may be more than compensated through losses in domestic EITE demand. - Highlights: • We assess impacts for US emission-intensive and trade-exposed (EITE) industries. • EITE impacts are quantified via competitiveness metrics and production output. • Protective measures reduce adverse competitiveness impacts but can depress output. • Output losses are due to negative income effects that reduce domestic EITE demand. • Protective measures run the risk of making US climate policy much more costly.

A G-protein β subunit, AGB1, negatively regulates the ABA response and drought tolerance by down-regulating AtMPK6-related pathway in Arabidopsis.

Directory of Open Access Journals (Sweden)

Dong-bei Xu

Full Text Available Heterotrimeric G-proteins are versatile regulators involved in diverse cellular processes in eukaryotes. In plants, the function of G-proteins is primarily associated with ABA signaling. However, the downstream effectors and the molecular mechanisms in the ABA pathway remain largely unknown. In this study, an AGB1 mutant (agb1-2 was found to show enhanced drought tolerance, indicating that AGB1 might negatively regulate drought tolerance in Arabidopsis. Data showed that AGB1 interacted with protein kinase AtMPK6 that was previously shown to phosphorylate AtVIP1, a transcription factor responding to ABA signaling. Our study found that transcript levels of three ABA responsive genes, AtMPK6, AtVIP1 and AtMYB44 (downstream gene of AtVIP1, were significantly up-regulated in agb1-2 lines after ABA or drought treatments. Other ABA-responsive and drought-inducible genes, such as RD29A (downstream gene of AtMYB44, were also up-regulated in agb1-2 lines. Furthermore, overexpression of AtVIP1 resulted in hypersensitivity to ABA at seed germination and seedling stages, and significantly enhanced drought tolerance in transgenic plants. These results suggest that AGB1 was involved in the ABA signaling pathway and drought tolerance in Arabidopsis through down-regulating the AtMPK6, AtVIP1 and AtMYB44 cascade.

CPC, a single-repeat R3 MYB, is a negative regulator of anthocyanin biosynthesis in Arabidopsis.

Science.gov (United States)

Zhu, Hui-Fen; Fitzsimmons, Karen; Khandelwal, Abha; Kranz, Robert G

2009-07-01

Single-repeat R3 MYB transcription factors like CPC (CAPRICE) are known to play roles in developmental processes such as root hair differentiation and trichome initiation. However, none of the six Arabidopsis single-repeat R3 MYB members has been reported to regulate flavonoid biosynthesis. We show here that CPC is a negative regulator of anthocyanin biosynthesis. In the process of using CPC to test GAL4-dependent driver lines, we observed a repression of anthocyanin synthesis upon GAL4-mediated CPC overexpression. We demonstrated that this is not due to an increase in nutrient uptake because of more root hairs. Rather, CPC expression level tightly controls anthocyanin accumulation. Microarray analysis on the whole genome showed that, of 37 000 features tested, 85 genes are repressed greater than three-fold by CPC overexpression. Of these 85, seven are late anthocyanin biosynthesis genes. Also, anthocyanin synthesis genes were shown to be down-regulated in 35S::CPC overexpression plants. Transient expression results suggest that CPC competes with the R2R3-MYB transcription factor PAP1/2, which is an activator of anthocyanin biosynthesis genes. This report adds anthocyanin biosynthesis to the set of programs that are under CPC control, indicating that this regulator is not only for developmental programs (e.g. root hairs, trichomes), but can influence anthocyanin pigment synthesis.

amiA is a negative regulator of acetamidase expression in Mycobacterium smegmatis

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Turner Jane

2001-08-01

Full Text Available Abstract Background The acetamidase of Mycobacterium smegmatis is a highly inducible enzyme. Expression of this enzyme is increased 100-fold when the substrate acetamide is present. The acetamidase gene is found immediately downstream of three open reading frames. Two of these are proposed to be involved in regulation. Results We constructed a deletion mutant in one of the upstream ORFs (amiA. This mutant (Mad1 showed a constitutively high level of acetamidase expression. We identified four promoters in the upstream region using a β-galactosidase reporter gene. One of these (P2 was inducible in the wild-type, but was constitutively active in Mad1. Conclusions These results demonstrate that amiA encodes a negative regulatory protein which interacts with P2. Since amiA has homology to DNA-binding proteins, it is likely that it exerts the regulatory effect by binding to the promoter to prevent transcription.

Sequence and function of LuxO, a negative regulator of luminescence in Vibrio harveyi.

Science.gov (United States)

Bassler, B L; Wright, M; Silverman, M R

1994-05-01

Density-dependent expression of luminescence in Vibrio harveyi is regulated by the concentration of extracellular signal molecules (autoinducers) in the culture medium. A recombinant clone that restored function to one class of spontaneous dim mutants was found to encode a function required for the density-dependent response. Transposon Tn5 insertions in the recombinant clone were isolated, and the mutations were transferred to the genome of V. harveyi for examination of mutant phenotypes. Expression of luminescence in V. harveyi strains with transposon insertions in one locus, luxO, was independent of the density of the culture and was similar in intensity to the maximal level observed in wild-type bacteria. Sequence analysis of luxO revealed one open reading frame that encoded a protein, LuxO, similar in amino acid sequence to the response regulator domain of the family of two-component, signal transduction proteins. The constitutive phenotype of LuxO- mutants indicates that LuxO acts negatively to control expression of luminescence, and relief of repression by LuxO in the wild type could result from interactions with other components in the Lux signalling system.

Environmental improvement with additional instruments for environmental protection in port areas

OpenAIRE

MARINSKI, Jordan; FLOQI, Tania; DROUMEVA, Gergana; BRANCA, Tatiana; VATRALOVA, Albena

2012-01-01

Abstract1. The context analysis of environmental situation in Corridor8 ports shows growing sensibility of the management authorities to the environmental issues and objective difficulties for development of appropriate environmental policies due to the following reasons: the complex legislation which has not found yet the balance between the business interests in sea transport and the environment protection and poor enforcement of the regulations. In order to mitigate the negative impact of ...

miR-375-3p negatively regulates osteogenesis by targeting and decreasing the expression levels of LRP5 and β-catenin.

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Tianhao Sun

Full Text Available Wnt signaling pathways are essential for bone formation. Previous studies showed that Wnt signaling pathways were regulated by miR-375. Thus, we aim to explore whether miR-375 could affect osteogenesis. In the present study, we investigated the roles of miR-375 and its downstream targets. Firstly, we revealed that miR-375-3p negatively modulated osteogenesis by suppressing positive regulators of osteogenesis and promoting negative regulators of osteogenesis. In addition, the results of TUNEL cell apoptosis assay showed that miR-375-3p induced MC3T3-E1 cell apoptosis. Secondly, miR-375-3p targeted low-density lipoprotein receptor-related protein 5 (LRP5, a co-receptor of the Wnt signaling pathways, and β-catenin as determined by luciferase activity assay, and it decreased the expression levels of LRP5 and β-catenin. Thirdly, the decline of protein levels of β-catenin was determined by immunocytochemistry and immunofluorescence. Finally, silence of LRP5 in osteoblast precursor cells resulted in diminished cell viability and cell proliferation as detected by WST-1-based colorimetric assay. Additionally, all the parameters including the relative bone volume from μCT measurement suggested that LRP5 knockout in mice resulted in a looser and worse-connected trabeculae. The mRNA levels of important negative modulators relating to osteogenesis increased after the functions of LRP5 were blocked in mice. Last but not least, the expression levels of LRP5 increased during the osteogenesis of MC3T3-E1, while the levels of β-catenin decreased in bone tissues from osteoporotic patients with vertebral compression fractures. In conclusion, we revealed miR-375-3p negatively regulated osteogenesis by targeting LRP5 and β-catenin. In addition, loss of functions of LRP5 damaged bone formation in vivo. Clinically, miR-375-3p and its targets might be used as diagnostic biomarkers for osteoporosis and might be also as novel therapeutic agents in osteoporosis

Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

Science.gov (United States)

Wu, Jing; Tao, Wei-Wei; Chong, Dan-Yang; Lai, Shan-Shan; Wang, Chuang; Liu, Qi; Zhang, Tong-Yu; Xue, Bin; Li, Chao-Jun

2018-03-15

Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity. Furthermore, deletion of Egr-1 in the skeletal muscle improved systemic insulin sensitivity and glucose tolerance, which resulted in lower blood glucose levels after refeeding. Mechanistic analysis demonstrated that EGR-1 inhibited InsR phosphorylation and glucose uptake in skeletal muscle by binding to the proximal promoter region of protein tyrosine phosphatase-1B (PTP1B) and directly activating transcription. PTP1B knockdown largely restored insulin sensitivity and enhanced glucose uptake, even under conditions of EGR-1 overexpression. Our results indicate that EGR-1/PTP1B signaling negatively regulates postprandial insulin sensitivity and suggest a potential therapeutic target for the prevention and treatment of excessive glucose absorption.-Wu, J., Tao, W.-W., Chong, D.-Y., Lai, S.-S., Wang, C., Liu, Q., Zhang, T.-Y., Xue, B., Li, C.-J. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

Institutionalizing environmental protection through self-regulation: the case of environmental standards adoption in Lithuania.

Science.gov (United States)

Bileisis, Mantas; Misiune, Ieva

2017-04-01

The impacts of human activity in the environment have a global dimension, but there are no effective global governance instruments to enforce environmental standards. At the same time, many national governments lack incentives to pursue strict environmental policies. In this context, self-regulation is seen as an alternative venue to address environmental challenges. This work aims to identify factors that influence companies to engage in environmental self-regulation? For this aim in March 2015 a survey of 482 companies was conducted. The target group were companies operating in Lithuania that hold ISO14001 certificates - one of the most prolific instruments for self-regulation. The questionnaire was designed to test assumptions developed in new institutionalist literature which claim that common practices can emerge through isomorphism.- The results showed that the main motive for environmental self-regulation is the desire to improve company image, rather than protecting the environment per se. Another important finding was that the main source of pressure to adopt self-regulation was based less on the perceived demands but the customers. Rather the driver for the adoption was a feeling of a need no to fall behind industry leaders. Thus, normative isomorphism is the main mechanism through which environmental self-regulation proliferates. We claim for a rapid proliferation of environmental self-regulation perceived industry leaders need to be identified and they need to be persuaded that environmental standards are key for the development of the industry. However, this also raises questions of sustainability. Few industries have long standing leaders, and through successful investment and technological development new actors can arise and this may risk stalling or even reversing self-regulation.

TRAF Family Member-Associated NF-κB Activator (TANK) Induced by RANKL Negatively Regulates Osteoclasts Survival and Function

OpenAIRE

Mengrui Wu, Yiping Wang, Lianfu Deng, Wei Chen, Yi-Ping Li

2012-01-01

Osteoclasts are the principle bone-resorbing cells. Precise control of balanced osteoclast activity is indispensable for bone homeostasis. Osteoclast activation mediated by RANK-TRAF6 axis has been clearly identified. However, a negative regulation-machinery in osteoclast remains unclear. TRAF family member-associated NF-κB activator (TANK) is induced by about 10 folds during osteoclastogenesis, according to a genome-wide analysis of gene expression before and after osteoclast maturation...

TRAF Family Member-Associated NF-κB Activator (TANK) Induced by RANKL Negatively Regulates Osteoclasts Survival and Function

OpenAIRE

Wu, Mengrui; Wang, Yiping; Deng, Lianfu; Chen, Wei; Li, Yi-Ping

2012-01-01

Osteoclasts are the principle bone-resorbing cells. Precise control of balanced osteoclast activity is indispensable for bone homeostasis. Osteoclast activation mediated by RANK-TRAF6 axis has been clearly identified. However, a negative regulation-machinery in osteoclast remains unclear. TRAF family member-associated NF-κB activator (TANK) is induced by about 10 folds during osteoclastogenesis, according to a genome-wide analysis of gene expression before and after osteoclast maturation, and...

The FasX Small Regulatory RNA Negatively Regulates the Expression of Two Fibronectin-Binding Proteins in Group A Streptococcus.

Science.gov (United States)

Danger, Jessica L; Makthal, Nishanth; Kumaraswami, Muthiah; Sumby, Paul

2015-12-01

The group A Streptococcus (GAS; Streptococcus pyogenes) causes more than 700 million human infections each year. The success of this pathogen can be traced in part to the extensive arsenal of virulence factors that are available for expression in temporally and spatially specific manners. To modify the expression of these virulence factors, GAS use both protein- and RNA-based regulators, with the best-characterized RNA-based regulator being the small regulatory RNA (sRNA) FasX. FasX is a 205-nucleotide sRNA that contributes to GAS virulence by enhancing the expression of the thrombolytic secreted virulence factor streptokinase and by repressing the expression of the collagen-binding cell surface pili. Here, we have expanded the FasX regulon, showing that this sRNA also negatively regulates the expression of the adhesion- and internalization-promoting, fibronectin-binding proteins PrtF1 and PrtF2. FasX posttranscriptionally regulates the expression of PrtF1/2 through a mechanism that involves base pairing to the prtF1 and prtF2 mRNAs within their 5' untranslated regions, overlapping the mRNA ribosome-binding sites. Thus, duplex formation between FasX and the prtF1 and prtF2 mRNAs blocks ribosome access, leading to an inhibition of mRNA translation. Given that FasX positively regulates the expression of the spreading factor streptokinase and negatively regulates the expression of the collagen-binding pili and of the fibronectin-binding PrtF1/2, our data are consistent with FasX functioning as a molecular switch that governs the transition of GAS between the colonization and dissemination stages of infection. More than half a million deaths each year are a consequence of infections caused by GAS. Insights into how this pathogen regulates the production of proteins during infection may facilitate the development of novel therapeutic or preventative regimens aimed at inhibiting this activity. Here, we have expanded insight into the regulatory activity of the GAS small

Protective interest rate as tax instrument of corporate capital protection

Directory of Open Access Journals (Sweden)

Vukašinović Jovan

2015-01-01

Full Text Available This paper deals with researching negative consequences of allocation of economic (virtual gains made as a result of conventional accounting concept by facing current income with historical expenses and necessity to promote additional stimulating instruments that are at disposal by the state in order to eliminate these negative consequences. one of them is certainly protective interest as a relatively new active fiscal instrument of capital protection and recognition of price of invested owner's equity in business ventures, i.e. a specific form of compensation by the state for invested capital bearing in mind, that no source is free, including ones own sources. We also showed mechanisms of protective interest which, together with other measures of macroeconomic policy, should contribute to the protection of real purchasing power of company equity and increase of net gain, left on company's disposal for new investments, new work places, more money in the budget, protection of actual assets against taxing in the conditions of inflation, etc.

33 CFR 165.1318 - Security and Safety Zone Regulations, Large Passenger Vessel Protection, Portland, OR Captain of...

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Security and Safety Zone Regulations, Large Passenger Vessel Protection, Portland, OR Captain of the Port Zone 165.1318 Section 165.1318 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND...

Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

Energy Technology Data Exchange (ETDEWEB)

Yang, Bin [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Li, Wei [Department of Gerontology, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Zheng, Qichang [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Qin, Tao [Department of Hepatobiliary Pancreatic Surgery, People' s Hospital of Zhengzhou University, School of Medicine, Zhengzhou University, Zhengzhou 450003 (China); Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Liu, Sanguang, E-mail: sanguang1998@sina.com [Department of Hepatobiliary Surgery, The Second Hospital, Hebei Medical University, Shijiazhuang 050000 (China); Song, Zifang, E-mail: zsong@hust.edu.cn [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China)

2015-07-17

Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation.

Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

International Nuclear Information System (INIS)

Yang, Bin; Li, Wei; Zheng, Qichang; Qin, Tao; Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen; Liu, Sanguang; Song, Zifang

2015-01-01

Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation

Evidence for the negative regulation of phytase gene expression in Streptomyces lividans and Streptomyces coelicolor.

Science.gov (United States)

Boukhris, Ines; Dulermo, Thierry; Chouayekh, Hichem; Virolle, Marie-Joëlle

2016-01-01

Sco7697, a gene encoding a phytase, enzyme able to degrade phytate (myo-inositol 1,2,3,4,5,6-hexakis phosphate), the most abundant phosphorus storing compound in plants is present in the genome of S. coelicolor, a soil born bacteria with a saprophytic lifestyle. The expression of this gene was previously shown to be induced in conditions of Pi limitation by the response regulator PhoP binding to an operator sequence, the PHO box, located upstream of the -35 promoter sequence. A close examination of the promoter region of sco7697 revealed the presence of another putative operator site, a Direct Repeat (DR), located downstream of the -10 promoter sequence. In order to determine whether this DR played a role in regulation of sco7697 expression, different variants of the phytase gene promoter region were transcriptionally fused to the ß-glucuronidase reporter gene (GUS). As expected, deletion of the PHO box led to abolition of sco7697 induction in conditions of Pi limitation. Interestingly, alteration of the DR correlated with a dramatic increase of GUS expression but only when PhoP was present. These results demonstrated that this DR is the site of strong negative regulation by an unknown repressor. The latter would impede the necessary activation of phytase expression by PhoP. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

No evidence for a protective effect of naturally induced HPV antibodies on subsequent anogenital HPV infection in HIV-negative and HIV-infected MSM

NARCIS (Netherlands)

Mooij, Sofie H.; Landén, Olivia; van der Klis, Fiona R. M.; van der Sande, Marianne A. B.; de Melker, Hester E.; Coutinho, Roel A.; van Eeden, Arne; van Rooijen, Martijn S.; Meijer, Chris J. L. M.; Schim van der Loeff, Maarten F.

2014-01-01

To assess whether HPV serum antibodies detected after natural infection protect against subsequent anal or penile infection with the same HPV type in HIV-negative and HIV-infected men who have sex with men (MSM). MSM aged ≥18 years were recruited in Amsterdam, the Netherlands (2010-2011), and

Radiation protection in Switzerland

International Nuclear Information System (INIS)

Brunner, H.

1990-01-01

Switzerland's present radiation protection regulations are based on only two paragraphs of the atomic law but have been very successful in practice. A new radiation protection law, separated from nuclear legislation and valid for all application of ionizing radiation and radioctive materials, was proposed and drafted by the Federal Commission on Radiation Protection and has now been accepted by parliament with only minor modifications. The draft of the revised regulations which also will cover all applications, should be ready for consultations next year. Both the law (which contains principles but no figures such as limits) and the regulations incorporate the latest state of ICRP recommendations and are formulated in such a way as to allow application of or quick adaptation to the new basic ICRP recommendation expected for 1991. The legislation is flexible, with a relatively low regulation density and leaves sufficient room for professional judgement on a case by case basis both for authorities and for the specialists responsible for radiation protection in practice. (orig./HSCH)

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

Science.gov (United States)

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

Negative regulation of parathyroid hormone-related protein expression by steroid hormones

International Nuclear Information System (INIS)

Kajitani, Takashi; Tamamori-Adachi, Mimi; Okinaga, Hiroko; Chikamori, Minoru; Iizuka, Masayoshi; Okazaki, Tomoki

2011-01-01

Highlights: → Steroid hormones repress expression of PTHrP in the cell lines where the corresponding nuclear receptors are expressed. → Nuclear receptors are required for suppression of PTHrP expression by steroid hormones, except for androgen receptor. → Androgen-induced suppression of PTHrP expression appears to be mediated by estrogen receptor. -- Abstract: Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor α, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression.

Radioactivity in drinking water: regulations, monitoring results and radiation protection issues

Directory of Open Access Journals (Sweden)

Cristina Nuccetelli

2012-12-01

Full Text Available INTRODUCTION: Drinking waters usually contain several natural radionuclides: tritium, radon, radium, uranium isotopes, etc. Their concentrations vary widely since they depend on the nature of the aquifer, namely, the prevailing lithology and whether there is air in it or not. AIMS: In this work a broad overview of the radioactivity in drinking water is presented: national and international regulations, for limiting the presence of radioactivity in waters intended for human consumption; results of extensive campaigns for monitoring radioactivity in drinking waters, including mineral bottled waters, carried out throughout the world in recent years; a draft of guidelines for the planning of campaigns to measure radioactivity in drinking water proposed by the Environmental Protection Agency (ARPA of Lombardia.

Post-translational regulation enables robust p53 regulation.

Science.gov (United States)

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

2013-08-30

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

Privacy in Digital Age: Dead or Alive?! Regarding the New EU Data Protection Regulations

Directory of Open Access Journals (Sweden)

Seyed Ebrahim Dorraji

2015-02-01

Full Text Available Purpose – To review and critically discuss the current state of privacy in the context of constant technological changes and to emphasize the pace of technological advancements and developments reached over the time when the last EU data protection laws came into effect. These facts inevitably affect the perception of privacy and raise the question of whether privacy is dead or takes the last breath in the digital age? This paper is an attempt to address this question.Design/Methodology/Approach – Based on the comparison and systematic analysis of scientific literature, the authors discuss problematic issues related to privacy and data protection in the technology era – where these issues are too complicated to be clearly regulated by laws and rules since “laws move as a function of years and technology moves as a function of months” (Ron Rivest. Therefore, this analytical approach towards the issue may help to facilitate reaching the best-fit decision in this area.Findings – The authors emphasize the change of perception of privacy, which originated and grew on the idea of “an integral part of our humanity”, the “heart of our liberty” and “the beginning of all freedoms” (Solove, 2008, leading to the recently raised idea that privacy is severely hanging with threat. The authors are of the opinion that legislation and regulation may be one of the best and effective techniques for protecting privacy in the twenty-first century, but it is not currently adequate (Wacks, 2012. One of the solutions lies in technology design.Research limitations/implications – The aspects of privacy and data protection in the European Union have been widely discussed recently because of their broad applicability. Therefore, it is hardly possible to review and cover all the important aspects of the issue. This article focuses on the roles of technology and legislation in securing privacy. The authors examine and provide their own views based on

Overexpression of O-polysaccharide chain length regulators in Gram-negative bacteria using the Wzx-/Wzy-dependent pathway enhances production of defined modal length O-polysaccharide polymers for use as haptens in glycoconjugate vaccines.

Science.gov (United States)

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.

About the necessity to update the Radiological safety and protection regulations of the National Institute of Nuclear Research (ININ)

International Nuclear Information System (INIS)

Alvarez R, J.T.

1997-01-01

It is argued the necessity to update the Radiological safety and Protection regulations (Review 3) of ININ, with the purpose that it implements the ICRU operative magnitudes system. Such a system used with radiological protection purposes. The objective of this system is to do an estimation of the effective equivalent dose H E and/or the Effective dose E, proposed in the ICRP 26 and ICRU 60 dose limits systems respectively. (Author)

The Swedish Radiation Protection Institute's regulations concerning the final management of spent nuclear fuel and nuclear waste - with background and comments

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-11-01

This report presents and comments on the Swedish Radiation Protection Institute's Regulations concerning the Protection of Human Health and the Environment in connection with the Final Management of Spent Nuclear Fuel or Nuclear Waste, SSI FS 1998: 1.

Ubiquitin carboxyl terminal hydrolase L1 negatively regulates TNFα-mediated vascular smooth muscle cell proliferation via suppressing ERK activation

International Nuclear Information System (INIS)

Ichikawa, Tomonaga; Li, Jinqing; Dong, Xiaoyu; Potts, Jay D.; Tang, Dong-Qi; Li, Dong-Sheng; Cui, Taixing

2010-01-01

Deubiquitinating enzymes (DUBs) appear to be critical regulators of a multitude of processes such as proliferation, apoptosis, differentiation, and inflammation. We have recently demonstrated that a DUB of ubiquitin carboxyl terminal hydrolase L1 (UCH-L1) inhibits vascular lesion formation via suppressing inflammatory responses in vasculature. However, the precise underlying mechanism remains to be defined. Herein, we report that a posttranscriptional up-regulation of UCH-L1 provides a negative feedback to tumor necrosis factor alpha (TNFα)-mediated activation of extracellular signal-regulated kinases (ERK) and proliferation in vascular smooth muscle cells (VSMCs). In rat adult VSMCs, adenoviral over-expression of UCH-L1 inhibited TNFα-induced activation of ERK and DNA synthesis. In contrast, over-expression of UCH-L1 did not affect platelet derived growth factor (PDGF)-induced VSMC proliferation and activation of growth stimulating cascades including ERK. TNFα hardly altered UCH-L1 mRNA expression and stability; however, up-regulated UCH-L1 protein expression via increasing UCH-L1 translation. These results uncover a novel mechanism by which UCH-L1 suppresses vascular inflammation.

Integrated expression analysis of muscle hypertrophy identifies Asb2 as a negative regulator of muscle mass

Science.gov (United States)

Davey, Jonathan R.; Watt, Kevin I.; Parker, Benjamin L.; Chaudhuri, Rima; Ryall, James G.; Cunningham, Louise; Qian, Hongwei; Sartorelli, Vittorio; Chamberlain, Jeffrey; James, David E.

2016-01-01

The transforming growth factor-β (TGF-β) signaling network is a critical regulator of skeletal muscle mass and function and, thus, is an attractive therapeutic target for combating muscle disease, but the underlying mechanisms of action remain undetermined. We report that follistatin-based interventions (which modulate TGF-β network activity) can promote muscle hypertrophy that ameliorates aging-associated muscle wasting. However, the muscles of old sarcopenic mice demonstrate reduced response to follistatin compared with healthy young-adult musculature. Quantitative proteomic and transcriptomic analyses of young-adult muscles identified a transcription/translation signature elicited by follistatin exposure, which included repression of ankyrin repeat and SOCS box protein 2 (Asb2). Increasing expression of ASB2 reduced muscle mass, thereby demonstrating that Asb2 is a TGF-β network–responsive negative regulator of muscle mass. In contrast to young-adult muscles, sarcopenic muscles do not exhibit reduced ASB2 abundance with follistatin exposure. Moreover, preventing repression of ASB2 in young-adult muscles diminished follistatin-induced muscle hypertrophy. These findings provide insight into the program of transcription and translation events governing follistatin-mediated adaptation of skeletal muscle attributes and identify Asb2 as a regulator of muscle mass implicated in the potential mechanistic dysfunction between follistatin-mediated muscle growth in young and old muscles. PMID:27182554

The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling

DEFF Research Database (Denmark)

Ungureanu, Daniela; Wu, Jinhua; Pekkala, Tuija

2011-01-01

Human JAK2 tyrosine kinase mediates signaling through numerous cytokine receptors. The JAK2 JH2 domain functions as a negative regulator and is presumed to be a catalytically inactive pseudokinase, but the mechanism(s) for its inhibition of JAK2 remains unknown. Mutations in JH2 lead to increased...... JAK2 activity, contributing to myeloproliferative neoplasms (MPNs). Here we show that JH2 is a dual-specificity protein kinase that phosphorylates two negative regulatory sites in JAK2: Ser523 and Tyr570. Inactivation of JH2 catalytic activity increased JAK2 basal activity and downstream signaling....... Notably, different MPN mutations abrogated JH2 activity in cells, and in MPN (V617F) patient cells phosphorylation of Tyr570 was reduced, suggesting that loss of JH2 activity contributes to the pathogenesis of MPNs. These results identify the catalytic activity of JH2 as a previously unrecognized...

International regulations on labour health and safety applied to fishing and maritime transport sectors. Are maritime workers under-protected.

Science.gov (United States)

Rodríguez, Julio Louro; Portela, Rosa Mary de la Campa; Pardo, Guadalupe Martín

2012-01-01

The work activity developed on board is of great importance in our nearby environment, and it has a series of peculiarities that determine the service rendering of sea workers. On the other hand, work at sea is developed on an international basis. Nowadays such work becomes a completely globalised industrial sector in relation to the elements that make up the ship's operation, including manpower. For that reason several relevant international organisations have paid attention to this industrial sector and have adopted a broad regulation on this matter. In the case of the European Union, the Community procedure emphasises enormous interest in providing specific and comprehensive training to seafarers, as well as in regulating working time on board with the aim of minimising the safety problems caused by fatigue. In the present article a schematic presentation of regulations on workers' health and occupational safety protection derived from the European Union, the International Maritime Organisation, and the International Labour Organisation has been done. Also it shows what parts of these regulations are not applicable to the work on board, and it reveals how the workers of fishing and maritime transport sectors are under-protected with regard to the guarantee of their health and occupational safety compared to workers in other sectors.

Expression of alkyl hydroperoxide reductase is regulated negatively by OxyR1 and positively by RpoE2 sigma factor in Azospirillum brasilense Sp7.

Science.gov (United States)

Singh, Sudhir; Dwivedi, Susheel Kumar; Singh, Vijay Shankar; Tripathi, Anil Kumar

2016-10-01

OxyR proteins are LysR-type transcriptional regulators, which play an important role in responding to oxidative stress in bacteria. Azospirillum brasilense Sp7 harbours two copies of OxyR. The inactivation of the oxyR1, the gene organized divergently to ahpC in A. brasilense Sp7, led to an increased tolerance to alkyl hydroperoxides, which was corroborated by an increase in alkyl hydroperoxide reductase (AhpC) activity, enhanced expression of ahpC :lacZ fusion and increased synthesis of AhpC protein in the oxyR1::km mutant. The upstream region of ahpC promoter harboured a putative OxyR binding site, T-N11-A. Mutation of T, A or both in the T-N11-Amotif caused derepression of ahpC in A. brasilense suggesting that T-N11-A might be the binding site for a negative regulator. Retardation of the electrophoretic mobility of the T-N11-A motif harbouring oxyR1-ahpC intergenic DNA by recombinant OxyR1, under reducing as well as oxidizing conditions, indicated that OxyR1 acts as a negative regulator of ahpC in A. brasilense. Sequence of the promoter of ahpC, predicted on the basis of transcriptional start site, and an enhanced expression of ahpC:lacZ fusion in chrR2::km mutant background suggested that ahpC promoter was RpoE2 dependent. Thus, this study shows that in A. brasilense Sp7, ahpC expression is regulated negatively by OxyR1 but is regulated positively by RpoE2, an oxidative-stress-responsive sigma factor. It also shows that OxyR1 regulates the expression RpoE1, which is known to play an important role during photooxidative stress in A. brasilense.

Hypothalamic PGC-1α Protects Against High-Fat Diet Exposure by Regulating ERα

Directory of Open Access Journals (Sweden)

Eugenia Morselli

2014-10-01

Full Text Available High-fat diets (HFDs lead to obesity and inflammation in the central nervous system (CNS. Estrogens and estrogen receptor α (ERα protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1α regulates ERα and inflammation in vivo. HFD significantly increased palmitic acid (PA and sphingolipids in the CNS of male mice when compared to female mice. PA, in vitro, and HFD, in vivo, reduced PGC-1α and ERα in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1α depletion with ERα overexpression significantly inhibited PA-induced inflammation, confirming that ERα is a critical determinant of the anti-inflammatory response. Physiologic relevance of ERα-regulated inflammation was demonstrated by reduced myocardial function in male, but not female, mice following chronic HFD exposure. Our findings show that HFD/PA reduces PGC-1α and ERα, promoting inflammation and decrements in myocardial function in a sex-specific way.

Hypothalamic PGC-1α protects against high-fat diet exposure by regulating ERα.

Science.gov (United States)

Morselli, Eugenia; Fuente-Martin, Esther; Finan, Brian; Kim, Min; Frank, Aaron; Garcia-Caceres, Cristina; Navas, Carlos Rodriguez; Gordillo, Ruth; Neinast, Michael; Kalainayakan, Sarada P; Li, Dan L; Gao, Yuanqing; Yi, Chun-Xia; Hahner, Lisa; Palmer, Biff F; Tschöp, Matthias H; Clegg, Deborah J

2014-10-23

High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor α (ERα) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1α regulates ERα and inflammation in vivo. HFD significantly increased palmitic acid (PA) and sphingolipids in the CNS of male mice when compared to female mice. PA, in vitro, and HFD, in vivo, reduced PGC-1α and ERα in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1α depletion with ERα overexpression significantly inhibited PA-induced inflammation, confirming that ERα is a critical determinant of the anti-inflammatory response. Physiologic relevance of ERα-regulated inflammation was demonstrated by reduced myocardial function in male, but not female, mice following chronic HFD exposure. Our findings show that HFD/PA reduces PGC-1α and ERα, promoting inflammation and decrements in myocardial function in a sex-specific way.

miR-146a negatively regulates the induction of proinflammatory cytokines in response to Japanese encephalitis virus infection in microglial cells.

Science.gov (United States)

Deng, Minnan; Du, Ganqin; Zhao, Jiegang; Du, Xiaowei

2017-06-01

Increasing evidence confirms the involvement of virus infection and miRNA, such as miR-146a, in neuroinflammation-associated epilepsy. In the present study, we investigated the upregulation of miR-146a with RT-qPCR and in situ hybridization methods in a mice infection model of Japanese encephalitis virus (JEV) and in vitro. Subsequently we investigated the involvement of miR-146a in modulating JEV-induced neuroinflammation. It was demonstrated that JEV infection promoted miR-146a production in BALB/c mice brain and in cultured mouse microglial C8-B4 cells, along with pro-inflammatory cytokines, such as IL-1β, IL-6, TNF-α, IFN-β and IFN-α. We also found that miR-146a exerted negative regulatory effects upon IL-1β, IL-6, TNF-α, IFN-β and IFN-α in C8-B4 cells. Accordingly, miR-146a downregulation with a miR-146a inhibitor promoted the upregulation of IL-1β, IL-6, TNF-α, IFN-β and IFN-α, whereas miR-146a upregulation with miR-146a mimics reduced the upregulation of these cytokines. Moreover, miR-146a exerted no regulation upon JEV growth in C8-B4 cells. In conclusion, JEV infection upregulated miR-146a and pro-inflammatory cytokine production, in mice brain and in cultured C8-B4 cells. Furthermore, miR-146a negatively regulated the production of JEV-induced pro-inflammatory cytokines, in virus growth independent fashion, identifying miR-146a as a negative feedback regulator in JEV-induced neuroinflammation, and possibly in epilepsy.

Complement receptor-3 negatively regulates the phagocytosis of degenerated myelin through tyrosine kinase Syk and cofilin

Directory of Open Access Journals (Sweden)

Hadas Smadar

2012-07-01

phosphorylated state of cofilin. Self-negative control of phagocytosis by the phagocytic receptor can be useful in protecting phagocytes from excessive phagocytosis (i.e., “overeating” during extended exposure to particles that are destined for ingestion.

Negative regulation of NOD1 mediated angiogenesis by PPARγ-regulated miR-125a

International Nuclear Information System (INIS)

Kang, Hyesoo; Park, Youngsook; Lee, Aram; Seo, Hyemin; Kim, Min Jung; Choi, Jihea; Jo, Ha-neul; Jeong, Ha-neul; Cho, Jin Gu; Chang, Woochul; Lee, Myeong-Sok; Jeon, Raok; Kim, Jongmin

2017-01-01

Infection with pathogens activates the endothelial cell and its sustained activation may result in impaired endothelial function. Endothelial dysfunction contributes to the pathologic angiogenesis that is characteristic of infection-induced inflammatory pathway activation. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a protein receptor which recognizes bacterial molecules and stimulates an immune reaction in various cells; however, the underlying molecular mechanisms in the regulation of inflammation-triggered angiogenesis are not fully understood. Here we report that peroxisome proliferator-activated receptor gamma (PPARγ)-mediated miR-125a serves as an important regulator of NOD1 agonist-mediated angiogenesis in endothelial cells by directly targeting NOD1. Treatment of human umbilical vein endothelial cells with natural PPARγ ligand, 15-Deoxy-Delta12,14-prostaglandin J2, led to inhibition of NOD1 expression; contrarily, protein levels of NOD1 were significantly increased by PPARγ knockdown. We report that PPARγ regulation of NOD1 expression is a novel microRNA-mediated regulation in endothelial cells. MiR-125a expression was markedly decreased in human umbilical vein endothelial cells subjected to PPARγ knockdown while 15-Deoxy-Delta12,14-prostaglandin J2 treatment increased the level of miR-125a. In addition, NOD1 is closely regulated by miR-125a, which directly targets the 3′ untranslated region of NOD1. Moreover, both overexpression of miR-125a and PPARγ activation led to inhibition of NOD1 agonist-induced tube formation in endothelial cells. Finally, NOD1 agonist increased the formation of cranial and subintestinal vessel plexus in zebrafish, and this effect was abrogated by concurrent PPARγ activation. Overall, these findings identify a PPARγ-miR-125a-NOD1 signaling axis in endothelial cells that is critical in the regulation of inflammation-mediated angiogenesis. - Highlights: • Expression of NOD1 is regulated by

Protecting Skeletal Muscle with Protein and Amino Acid during Periods of Disuse

Directory of Open Access Journals (Sweden)

Elfego Galvan

2016-07-01

Full Text Available Habitual sedentary behavior increases risk of chronic disease, hospitalization and poor quality of life. Short-term bed rest or disuse accelerates the loss of muscle mass, function, and glucose tolerance. Optimizing nutritional practices and protein intake may reduce the consequences of disuse by preserving metabolic homeostasis and muscle mass and function. Most modes of physical inactivity have the potential to negatively impact the health of older adults more than their younger counterparts. Mechanistically, mammalian target of rapamycin complex 1 (mTORC1 signaling and muscle protein synthesis are negatively affected by disuse. This contributes to reduced muscle quality and is accompanied by impaired glucose regulation. Simply encouraging increased protein and/or energy consumption is a well-intentioned, but often impractical strategy to protect muscle health. Emerging evidence suggests that leucine supplemented meals may partially and temporarily protect skeletal muscle during disuse by preserving anabolism and mitigating reductions in mass, function and metabolic homeostasis.

The protective role of maternal posttraumatic growth and cognitive trauma processing among Palestinian mothers and infants.

Science.gov (United States)

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.

Further European initiatives and regulations concerning radiation protection: drinking water guideline, maximum permissible contamination in food products and feeding stuff; Weitere europaeische Initiativen und Regelungen im Strahlenschutz. Trinkwasserrichtlinie, maximal zulaessige Kontaminationswerte in Nahrungs- und Futtermitteln

Energy Technology Data Exchange (ETDEWEB)

Mundigl, Stefan [Europaeische Kommission, Generaldirektion Energie, Luxemburg (Luxembourg). Abt. D3 - Strahlenschutz, EUFO 4150

2013-07-01

The radiation protection community has observed intensively the development of basic safety standards concerning protection against hazards of ionizing radiation. The new core part of the European radiation protection legislation is complemented by several specialized regulations relevant for radiation protection. Besides the existing regulations in the field of emergency protection the European Commission initiated a drinking water guideline that will be published in the near future. Furthermore the European commission approved a revised regulation concerning the maximum permissible contamination limits for food products and feeding stuff in case of a future nuclear accident. Together with the new radiation protection basic standards a new complete, coherent and modernized European regulation package will be accomplished.

Src-family kinases negatively regulate NFAT signaling in resting human T cells.

Directory of Open Access Journals (Sweden)

Alan Baer

Full Text Available T cell signaling is required for activation of both natural and therapeutic T cells including chimeric antigen receptor (CAR T cells. Identification of novel factors and pathways regulating T cell signaling may aid in development of effective T cell therapies. In resting human T cells, the majority of Src-family of tyrosine kinases (SFKs are inactive due to phosphorylation of a conserved carboxy-terminal tyrosine residue. Recently, a pool of enzymatically active SFKs has been identified in resting T cells; however, the significance of these is incompletely understood. Here, we characterized the role of active SFKs in resting human T cells. Pharmacologic inhibition of active SFKs enhanced distal TCR signaling as measured by IL-2 release and CD25 surface expression following TCR-independent activation. Mechanistically, inhibition of the active pool of SFKs induced nuclear translocation of NFAT1, and enhanced NFAT1-dependent signaling in resting T cells. The negative regulation of NFAT1 signaling was in part mediated by the Src-kinase Lck as human T cells lacking Lck had increased levels of nuclear NFAT1 and demonstrated enhanced NFAT1-dependent gene expression. Inhibition of active SFKs in resting primary human T cells also increased nuclear NFAT1 and enhanced NFAT1-dependent signaling. Finally, the calcineurin inhibitor FK506 and Cyclosporin A reversed the effect of SFKs inhibition on NFAT1. Together, these data identified a novel role of SFKs in preventing aberrant NFAT1 activation in resting T cells, and suggest that maintaining this pool of active SFKs in therapeutic T cells may increase the efficacy of T cell therapies.

An unusual spliced variant of DELLA protein, a negative regulator of gibberellin signaling, in lettuce.

Science.gov (United States)

Sawada, Yoshiaki; Umetsu, Asami; Komatsu, Yuki; Kitamura, Jun; Suzuki, Hiroyuki; Asami, Tadao; Fukuda, Machiko; Honda, Ichiro; Mitsuhashi, Wataru; Nakajima, Masatoshi; Toyomasu, Tomonobu

2012-01-01

DELLA proteins are negative regulators of the signaling of gibberellin (GA), a phytohormone regulating plant growth. DELLA degradation is triggered by its interaction with GID1, a soluble GA receptor, in the presence of bioactive GA. We isolated cDNA from a spliced variant of LsDELLA1 mRNA in lettuce, and named it LsDELLA1sv. It was deduced that LsDELLA1sv encodes truncated LsDELLA1, which has DELLA and VHYNP motifs at the N terminus but lacks part of the C-terminal GRAS domain. The recombinant LsDELLA1sv protein interacted with both Arabidopsis GID1 and lettuce GID1s in the presence of GA. A yeast two-hybrid assay suggested that LsDELLA1sv interacted with LsDELLA1. The ratio of LsDELLA1sv to LsDELLA1 transcripts was higher in flower samples at the late reproductive stage and seed samples (dry seeds and imbibed seeds) than in the other organ samples examined. This study suggests that LsDELLA1sv is a possible modulator of GA signaling in lettuce.

Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders.

Science.gov (United States)

Gery, Sigal; Gueller, Saskia; Chumakova, Katya; Kawamata, Norihiko; Liu, Liqin; Koeffler, H Phillip

2007-11-01

Recently, activating myeloproliferative leukemia virus oncogene (MPL) mutations, MPLW515L/K, were described in myeloproliferative disorder (MPD) patients. MPLW515L leads to activation of downstream signaling pathways and cytokine-independent proliferation in hematopoietic cells. The adaptor protein Lnk is a negative regulator of several cytokine receptors, including MPL. We show that overexpression of Lnk in Ba/F3-MPLW515L cells inhibits cytokine-independent growth, while suppression of Lnk in UT7-MPLW515L cells enhances proliferation. Lnk blocks the activation of Jak2, Stat3, Erk, and Akt in these cells. Furthermore, MPLW515L-expressing cells are more susceptible to Lnk inhibitory functions than their MPL wild-type (MPLWT)-expressing counterparts. Lnk associates with activated MPLWT and MPLW515L and colocalizes with the receptors at the plasma membrane. The SH2 domain of Lnk is essential for its binding and for its down-regulation of MPLWT and MPLW515L. Lnk itself is tyrosine-phosphorylated following thrombopoietin stimulation. Further elucidating the cellular pathways that attenuate MPLW515L will provide insight into the pathogenesis of MPD and could help develop specific therapeutic approaches.

Clinical protection against caprine herpesvirus 1 genital infection by intranasal administration of a live attenuated glycoprotein E negative bovine herpesvirus 1 vaccine

Directory of Open Access Journals (Sweden)

Meurens François

2007-12-01

Full Text Available Abstract Background Caprine herpesvirus 1 (CpHV-1 is responsible of systemic diseases in kids and genital diseases leading to abortions in goats. CpHV-1 is widespread and especially in Mediterranean countries as Greece, Italy and Spain. CpHV-1 is antigenically and genetically closely related to bovine herpesvirus 1 (BoHV-1. Taking into account the biological properties shared by these two viruses, we decided in the current study to assess the protection of a live attenuated glycoprotein E (gE negative BoHV-1 vaccine against a genital CpHV-1 infection in goats. Results The vaccine was inoculated intranasally twice three weeks apart followed by a subsequent CpHV-1 intravaginal challenge which is the natural route of infection in three goats. To analyse the safety and the efficacy of this marker vaccine, two groups of three goats served as controls: one immunised with a virulent CpHV-1 and one uninoculated until the challenge. Goats were clinically monitored and all sampling procedures were carried out in a blind manner. The vaccine did not induce any undesirable local or systemic reaction and goats did not excrete gE-negative BoHV-1. After challenge, a significant reduction in disease severity was observed in immunised goats. Moreover, goats immunised with either gE-negative BoHV-1 or CpHV-1 exhibited a significant reduction in the length and the peak of viral excretion. Antibodies neutralising both BoHV-1 and CpHV-1 were raised in immunised goats. Conclusion Intranasal application of a live attenuated gE-negative BoHV-1 vaccine is able to afford a clinical protection and a reduction of virus excretion in goats challenged by a CpHV-1 genital infection.

Salt Stress Represses Soybean Seed Germination by Negatively Regulating GA Biosynthesis While Positively Mediating ABA Biosynthesis.

Science.gov (United States)

Shu, Kai; Qi, Ying; Chen, Feng; Meng, Yongjie; Luo, Xiaofeng; Shuai, Haiwei; Zhou, Wenguan; Ding, Jun; Du, Junbo; Liu, Jiang; Yang, Feng; Wang, Qiang; Liu, Weiguo; Yong, Taiwen; Wang, Xiaochun; Feng, Yuqi; Yang, Wenyu

2017-01-01

Soybean is an important and staple oilseed crop worldwide. Salinity stress has adverse effects on soybean development periods, especially on seed germination and post-germinative growth. Improving seed germination and emergence will have positive effects under salt stress conditions on agricultural production. Here we report that NaCl delays soybean seed germination by negatively regulating gibberellin (GA) while positively mediating abscisic acid (ABA) biogenesis, which leads to a decrease in the GA/ABA ratio. This study suggests that fluridone (FLUN), an ABA biogenesis inhibitor, might be a potential plant growth regulator that can promote soybean seed germination under saline stress. Different soybean cultivars, which possessed distinct genetic backgrounds, showed a similar repressed phenotype during seed germination under exogenous NaCl application. Biochemical analysis revealed that NaCl treatment led to high MDA (malondialdehyde) level during germination and the post-germinative growth stages. Furthermore, catalase, superoxide dismutase, and peroxidase activities also changed after NaCl treatment. Subsequent quantitative Real-Time Polymerase Chain Reaction analysis showed that the transcription levels of ABA and GA biogenesis and signaling genes were altered after NaCl treatment. In line with this, phytohormone measurement also revealed that NaCl considerably down-regulated active GA 1 , GA 3 , and GA 4 levels, whereas the ABA content was up-regulated; and therefore ratios, such as GA 1 /ABA, GA 3 /ABA, and GA 4 /ABA, are decreased. Consistent with the hormonal quantification, FLUN partially rescued the delayed-germination phenotype caused by NaCl-treatment. Altogether, these results demonstrate that NaCl stress inhibits soybean seed germination by decreasing the GA/ABA ratio, and that FLUN might be a potential plant growth regulator that could promote soybean seed germination under salinity stress.

Salt Stress Represses Soybean Seed Germination by Negatively Regulating GA Biosynthesis While Positively Mediating ABA Biosynthesis

Directory of Open Access Journals (Sweden)

Kai Shu

2017-08-01

Full Text Available Soybean is an important and staple oilseed crop worldwide. Salinity stress has adverse effects on soybean development periods, especially on seed germination and post-germinative growth. Improving seed germination and emergence will have positive effects under salt stress conditions on agricultural production. Here we report that NaCl delays soybean seed germination by negatively regulating gibberellin (GA while positively mediating abscisic acid (ABA biogenesis, which leads to a decrease in the GA/ABA ratio. This study suggests that fluridone (FLUN, an ABA biogenesis inhibitor, might be a potential plant growth regulator that can promote soybean seed germination under saline stress. Different soybean cultivars, which possessed distinct genetic backgrounds, showed a similar repressed phenotype during seed germination under exogenous NaCl application. Biochemical analysis revealed that NaCl treatment led to high MDA (malondialdehyde level during germination and the post-germinative growth stages. Furthermore, catalase, superoxide dismutase, and peroxidase activities also changed after NaCl treatment. Subsequent quantitative Real-Time Polymerase Chain Reaction analysis showed that the transcription levels of ABA and GA biogenesis and signaling genes were altered after NaCl treatment. In line with this, phytohormone measurement also revealed that NaCl considerably down-regulated active GA1, GA3, and GA4 levels, whereas the ABA content was up-regulated; and therefore ratios, such as GA1/ABA, GA3/ABA, and GA4/ABA, are decreased. Consistent with the hormonal quantification, FLUN partially rescued the delayed-germination phenotype caused by NaCl-treatment. Altogether, these results demonstrate that NaCl stress inhibits soybean seed germination by decreasing the GA/ABA ratio, and that FLUN might be a potential plant growth regulator that could promote soybean seed germination under salinity stress.

The role of emotion regulation in situational empathy-related responding and prosocial behaviour in the presence of negative affect.

Science.gov (United States)

Hein, Sascha; Röder, Mandy; Fingerle, Michael

2016-12-15

Empathy and prosocial behaviour are crucial factors for children's positive social adjustment. Contemporary models of empathy highlight the capacity to regulate vicariously experienced emotions as a precursor to empathy-related responses (e.g., prosocial behaviour). The goal of this study was to examine the role of emotion regulation (ER) in situational empathy-related responding and prosocial behaviour. A sample of 157 children (76 boys and 81 girls; M age = 9.94 years) participated in a two-tiered interview procedure that utilised vignettes to assess empathy and prosocial behaviour. Between both phases of the interview, a negative affect was induced to investigate the influence of ER on the change between the two phases. Results from a latent change model showed that ER strategies positively predicted change scores, that is, children with higher abilities to regulate emotions showed a higher increase in empathy and prosocial behaviour. Implications for the promotion of social-emotional learning in school are discussed. © 2016 International Union of Psychological Science.

A negative regulation loop of long noncoding RNA HOTAIR and p53 in non-small-cell lung cancer

Directory of Open Access Journals (Sweden)

Zhai N

2016-09-01

Full Text Available Nailiang Zhai,1 Yongfu Xia,1 Rui Yin,2 Jinping Liu,3 Fuquan Gao1 1Department of Respiratory Medicine, Affiliated Hospital of Binzhou Medical University, 2Department of Respiratory Medicine, People’s Hospital of Binzhou City, 3Department of Pharmacology, Binzhou Medical University, Binzhou, Shandong, People’s Republic of China Abstract: Non-small-cell lung cancer (NSCLC is one of the leading causes of cancer-related death worldwide, and the 5-year survival rate is still low despite advances in diagnosis and therapeutics. A long noncoding RNA (lncRNA HOX antisense intergenic RNA (HOTAIR has been revealed to play important roles in NSCLC carcinogenesis but the detailed mechanisms are still unclear. In the current study, we aimed to investigate the regulation between the lncRNA HOTAIR and p53 in the NSCLC patient samples and cell lines. Our results showed that HOTAIR expression was significantly higher in the cancer tissues than that in the adjacent normal tissue, and was negatively correlated with p53 functionality rather than expression. When p53 was overexpressed in A549 cells, the lncRNA HOTAIR expression was downregulated, and the cell proliferation rate and cell invasion capacity decreased as a consequence. We identified two binding sites of p53 on the promoter region of HOTAIR, where the p53 protein would bind to and suppress the HOTAIR mRNA transcription. Inversely, overexpression of lncRNA HOTAIR inhibited the expression of p53 in A549 cells. Mechanistic studies revealed that HOTAIR modified the promoter of p53 and enhanced histone H3 lysine 27 trimethylation (H3K27me3. These studies identified a specific negative regulation loop of lncRNA HOTAIR and p53 in NSCLC cells, which revealed a new understanding of tumorigenesis in p53 dysfunction NSCLC cells. Keywords: NSCLC, LncRNA HOTAIR, p53, negative loop

Protection algorithm for a wind turbine generator based on positive- and negative-sequence fault components

DEFF Research Database (Denmark)

Zheng, Tai-Ying; Cha, Seung-Tae; Crossley, Peter A.

2011-01-01

A protection relay for a wind turbine generator (WTG) based on positive- and negative-sequence fault components is proposed in the paper. The relay uses the magnitude of the positive-sequence component in the fault current to detect a fault on a parallel WTG, connected to the same power collection...... feeder, or a fault on an adjacent feeder; but for these faults, the relay remains stable and inoperative. A fault on the power collection feeder or a fault on the collection bus, both of which require an instantaneous tripping response, are distinguished from an inter-tie fault or a grid fault, which...... in the fault current is used to decide on either instantaneous or delayed operation. The operating performance of the relay is then verified using various fault scenarios modelled using EMTP-RV. The scenarios involve changes in the position and type of fault, and the faulted phases. Results confirm...

Pentazocine Protects SN4741 Cells Against MPP+-Induced Cell Damage via Up-Regulation of the Canonical Wnt/β-Catenin Signaling Pathway

Directory of Open Access Journals (Sweden)

Jiancai Wang

2017-06-01

Full Text Available The Wnt/β-catenin signaling pathway has been linked to many neurodegenerative diseases including Parkinson’s disease (PD. A glycoprotein named Dickkopf-1 (Dkk1 can combine with the receptor complex on cell membrane to inhibit Wnt/β-catenin signaling. Opioids, a series of compounds including morphine, fentanyl and pentazocine, have been reported to contribute to the up-regulation of Wnt/β-catenin signaling. Naloxone is an antagonist that has been used as an antidote to opioids through mu-opioid receptor. 1-methyl-4-phenylpyridinium (MPP+, which serves as a selective toxin for dopaminergic neurons, has been used to create experimental models of PD. In our study, we examined the protective effects of pentazocine against MPP+-induced cell death in the nigral dopaminergic cell line, SN4741 and tried to elucidate the molecular mechanisms underlying such protective effects. The data showed that pretreatment with pentazocine significantly rescued the SN4741 cell against MPP+. Moreover, the MPP+-exposed SN4741 cells exhibited a down-regulation of β-catenin, which could be restored by treatment with pentazocine. However, Dkk1 but not naloxonewas associated with the abrogation of protective effect of pentazocine. These results suggest that pentazocine alleviates MPP+-induced SN4741 cells apoptosis via the up-regulation of canonical Wnt/β-catenin signaling.

Radiation protection as part of occupational health and safety in the regulation of uranium mines in Canada

International Nuclear Information System (INIS)

Dory, A.B.

1982-01-01

The author establishes that radiation exposure is one of the health hazards of uranium mining and therefore has to be controlled. The jurisdictional framework for this is outlined and the role and functions of the Atomic Energy Control Board are detailed. The author then sets down seven objectives for radiation protection followed by an outline of the Canadian regulatory philosophy including an examination of two possible approaches to regulation of uranium mining and milling, and a sketch of pending new regulations. After setting down what he considers the main concerns of the AECB in mine regulation, the author details the Board's licensing process, compliance activities and relationship with workers. The conclusion includes a call for a more rational approach in considering and therefore dealing with radiation as a workplace hazard

Effective environmental protection by the reform of the administrative procedures and administrative legal rights

International Nuclear Information System (INIS)

Breuer, R.

1978-01-01

The 52nd German Lawyers Meeting will be concerned in its legal department with the question of whether, from the points of view of the guaranteeing of the necessary environmental protection, additional regulations in the administrative procedures and administrative legal rights should be recommended. Here one is concerned, above all, with the problem of whether an administrative legal associations sueing or associations participation in administrative legal procedures is desirable in the interests of environmental protection. A negative answer must be given to this question. Discussion should concentrate on the problematical administrative legal interests, on the strengthening of administrative participation of popular opinion or interests in legal processes, on other improvements in administrative processes and on the legal control by Parliament of environmental protection. (orig.) [de

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

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Lixia Gou

2017-11-01

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

SIRT6 Acts as a Negative Regulator in Dengue Virus-Induced Inflammatory Response by Targeting the DNA Binding Domain of NF-κB p65

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Pengcheng Li

2018-04-01

Full Text Available Dengue virus (DENV is a mosquito-borne single-stranded RNA virus causing human disease with variable severity. The production of massive inflammatory cytokines in dengue patients has been associated with dengue disease severity. However, the regulation of these inflammatory responses remains unclear. In this study, we report that SIRT6 is a negative regulator of innate immune responses during DENV infection. Silencing of Sirt6 enhances DENV-induced proinflammatory cytokine and chemokine production. Overexpression of SIRT6 inhibits RIG-I-like receptor (RLR and Toll-like receptor 3 (TLR3 mediated NF-κB activation. The sirtuin core domain of SIRT6 is required for the inhibition of NF-κB p65 function. SIRT6 interacts with the DNA binding domain of p65 and competes with p65 to occupy the Il6 promoter during DENV infection. Collectively, our study demonstrates that SIRT6 negatively regulates DENV-induced inflammatory response via RLR and TLR3 signaling pathways.

Impaired down-regulation of negative emotion in self-referent social situations in bipolar disorder: A pilot study of a novel experimental paradigm.

Science.gov (United States)

Kjærstad, Hanne L; Vinberg, Maj; Goldin, Philippe R; Køster, Nicolai; Støttrup, Mette Marie D; Knorr, Ulla; Kessing, Lars V; Miskowiak, Kamilla W

2016-04-30

Emotion dysregulation is a core feature of bipolar disorder (BD) that persists into periods of remission. Neuroimaging studies show aberrant neural responses during emotion regulation (ER) in patients with BD relative to healthy controls, but behavioural evidence for ER deficits is sparse and conflicting. This study aimed to explore ER in BD using a novel, personally relevant experimental paradigm. Twenty patients with BD and 20 patients with unipolar disorder (UD), in full or partial remission, and 20 healthy controls were given a novel computerised test. Participants were instructed to react naturally or dampen their emotional response to positive and negative social scenarios and associated self-beliefs. They were also given an established experimental task for comparison, involving reappraisal of negative affective picture stimuli, as well as a questionnaire of habitual ER strategies. BD patients showed reduced ability to down-regulate emotional responses in negative, but not positive, social scenarios relative to healthy controls and UD patients. In contrast, there were no between-group differences in the established ER task or in self-reported habitual reappraisal strategies. Findings highlight the novel social scenario paradigm as a sensitive test for detection of ER difficulties in BD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Gibberellin Application at Pre-Bloom in Grapevines Down-Regulates the Expressions of VvIAA9 and VvARF7, Negative Regulators of Fruit Set Initiation, during Parthenocarpic Fruit Development

Science.gov (United States)

Jung, Chan Jin; Hur, Youn Young; Yu, Hee-Ju; Noh, Jung-Ho; Park, Kyo-Sun; Lee, Hee Jae

2014-01-01

Fruit set is initiated only after fertilization and is tightly regulated primarily by gibberellins (GAs) and auxins. The application of either of these hormones induces parthenocarpy, fruit set without fertilization, but the molecular mechanism underlying this induction is poorly understood. In the present study, we have shown that the parthenocarpic fruits induced by GA application at pre-bloom result from the interaction of GA with auxin signaling. The transcriptional levels of the putative negative regulators of fruit set initiation, including Vitis auxin/indole-3-acetic acid transcription factor 9 (VvIAA9), Vitis auxin response factor 7 (VvARF7), and VvARF8 were monitored during inflorescence development in seeded diploid ‘Tamnara’ grapevines with or without GA application. Without GA application, VvIAA9, VvARF7, and VvARF8 were expressed at a relatively high level before full bloom, but decreased thereafter following pollination. After GA application at 14 days before full bloom (DBF); however, the expression levels of VvIAA9 and VvARF7 declined at 5 DBF prior to pollination. The effects of GA application on auxin levels or auxin signaling were also analyzed by monitoring the expression patterns of auxin biosynthesis genes and auxin-responsive genes with or without GA application. Transcription levels of the auxin biosynthesis genes Vitis anthranilate synthase β subunit (VvASB1-like), Vitis YUCCA2 (VvYUC2), and VvYUC6 were not significantly changed by GA application. However, the expressions of Vitis Gretchen Hagen3.2 (VvGH3.2) and VvGH3.3, auxin-responsive genes, were up-regulated from 2 DBF to full bloom with GA application. Furthermore, the Vitis GA signaling gene, VvDELLA was up-regulated by GA application during 12 DBF to 7 DBF, prior to down-regulation of VvIAA9 and VvARF7. These results suggest that VvIAA9 and VvARF7 are negative regulators of fruit set initiation in grapevines, and GA signaling is integrated with auxin signaling via VvDELLA during

Ethical issues in radiation protection

International Nuclear Information System (INIS)

Persson, Lars

2000-03-01

Ethical theories are relevant to the current recommendations and standards for radiation protection. Radiation protection is not only a matter for science. It is also a problem of philosophy. In order for protection regulations to be respected, it must correspond to widely accepted ethical values among those who are affected by the regulations. The workshop covered the following issues: Problems in Present Protection Policy, ICRP Protection Policy - A Historical Perspective, Radiation Risk - What we know and what we believe, Present ICRP Recommendations, Ethical Values in the Context of ICRP Recommendations, Collective Responsibility for Invisible Harm, Environmental Protection - Ethical Issues, The Global Change of Values, and Procedural justice and Radiation Protection. Six workshop contributions and a workshop summary are presented in this report

Ethical issues in radiation protection

Energy Technology Data Exchange (ETDEWEB)

Persson, Lars (ed.)

2000-03-15

Ethical theories are relevant to the current recommendations and standards for radiation protection. Radiation protection is not only a matter for science. It is also a problem of philosophy. In order for protection regulations to be respected, it must correspond to widely accepted ethical values among those who are affected by the regulations. The workshop covered the following issues: Problems in Present Protection Policy, ICRP Protection Policy - A Historical Perspective, Radiation Risk - What we know and what we believe, Present ICRP Recommendations, Ethical Values in the Context of ICRP Recommendations, Collective Responsibility for Invisible Harm, Environmental Protection - Ethical Issues, The Global Change of Values, and Procedural justice and Radiation Protection. Six workshop contributions and a workshop summary are presented in this report.

Royal Order of 5 December 1975 amending the Royal Order of 11 May 1971 embodying the general Military Regulations for Protection Against the Hazards of Ionizing Radiations

International Nuclear Information System (INIS)

1975-01-01

This Royal Order amends the Royal Order on general Military Regulations for Protection against the Hazards of Ionizing Radiations to bring it into line with the Royal Order of 23 December 1970, amending the general Regulations for Protection of the Population and Workers against the Hazards of Ionizing Radiations of 28 February 1963, subject to certain adaptations specific to military activities. (NEA) [fr

An Arabidopsis SUMO E3 Ligase, SIZ1, Negatively Regulates Photomorphogenesis by Promoting COP1 Activity

KAUST Repository

Lin, Xiao-Li; Niu, De; Hu, Zi-Liang; Kim, Dae Heon; Jin, Yin Hua; Cai, Bin; Liu, Peng; Miura, Kenji; Yun, Dae-Jin; Kim, Woe-Yeon; Lin, Rongcheng; Jin, Jing Bo

2016-01-01

COP1 (CONSTITUTIVE PHOTOMORPHOGENIC 1), a ubiquitin E3 ligase, is a central negative regulator of photomorphogenesis. However, how COP1 activity is regulated by post-translational modifications remains largely unknown. Here we show that SUMO (small ubiquitin-like modifier) modification enhances COP1 activity. Loss-of-function siz1 mutant seedlings exhibit a weak constitutive photomorphogenic phenotype. SIZ1 physically interacts with COP1 and mediates the sumoylation of COP1. A K193R substitution in COP1 blocks its SUMO modification and reduces COP1 activity in vitro and in planta. Consistently, COP1 activity is reduced in siz1 and the level of HY5, a COP1 target protein, is increased in siz1. Sumoylated COP1 may exhibits higher transubiquitination activity than does non-sumoylated COP1, but SIZ1-mediated SUMO modification does not affect COP1 dimerization, COP1-HY5 interaction, and nuclear accumulation of COP1. Interestingly, prolonged light exposure reduces the sumoylation level of COP1, and COP1 mediates the ubiquitination and degradation of SIZ1. These regulatory mechanisms may maintain the homeostasis of COP1 activity, ensuing proper photomorphogenic development in changing light environment. Our genetic and biochemical studies identify a function for SIZ1 in photomorphogenesis and reveal a novel SUMO-regulated ubiquitin ligase, COP1, in plants.

An Arabidopsis SUMO E3 Ligase, SIZ1, Negatively Regulates Photomorphogenesis by Promoting COP1 Activity

KAUST Repository

Lin, Xiao-Li

2016-04-29

COP1 (CONSTITUTIVE PHOTOMORPHOGENIC 1), a ubiquitin E3 ligase, is a central negative regulator of photomorphogenesis. However, how COP1 activity is regulated by post-translational modifications remains largely unknown. Here we show that SUMO (small ubiquitin-like modifier) modification enhances COP1 activity. Loss-of-function siz1 mutant seedlings exhibit a weak constitutive photomorphogenic phenotype. SIZ1 physically interacts with COP1 and mediates the sumoylation of COP1. A K193R substitution in COP1 blocks its SUMO modification and reduces COP1 activity in vitro and in planta. Consistently, COP1 activity is reduced in siz1 and the level of HY5, a COP1 target protein, is increased in siz1. Sumoylated COP1 may exhibits higher transubiquitination activity than does non-sumoylated COP1, but SIZ1-mediated SUMO modification does not affect COP1 dimerization, COP1-HY5 interaction, and nuclear accumulation of COP1. Interestingly, prolonged light exposure reduces the sumoylation level of COP1, and COP1 mediates the ubiquitination and degradation of SIZ1. These regulatory mechanisms may maintain the homeostasis of COP1 activity, ensuing proper photomorphogenic development in changing light environment. Our genetic and biochemical studies identify a function for SIZ1 in photomorphogenesis and reveal a novel SUMO-regulated ubiquitin ligase, COP1, in plants.

Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes.

Science.gov (United States)

Li, Xian; Lee, Youn Ju; Jin, Fansi; Park, Young Na; Deng, Yifeng; Kang, Youra; Yang, Ju Hye; Chang, Jae-Hoon; Kim, Dong-Young; Kim, Jung-Ae; Chang, Young-Chae; Ko, Hyun-Jeong; Kim, Cheorl-Ho; Murakami, Makoto; Chang, Hyeun Wook

2017-07-25

Sirt1, a key regulator of metabolism and longevity, has recently been implicated in the regulation of allergic reactions, although the underlying mechanism remains unclear. Here we show that Sirt1 negatively regulates FcεRI-stimulated mast cell activation and anaphylaxis through two mutually regulated pathways involving AMP-activated protein kinase (AMPK) and protein tyrosine phosphatase 1B (PTP1B). Mast cell-specific knockout of Sirt1 dampened AMPK-dependent suppression of FcεRI signaling, thereby augmenting mast cell activation both in vitro and in vivo. Sirt1 inhibition of FcεRI signaling also involved an alternative component, PTP1B, which attenuated the inhibitory AMPK pathway and conversely enhanced the stimulatory Syk pathway, uncovering a novel role of this phosphatase. Moreover, a Sirt1 activator resveratrol stimulated the inhibitory AMPK axis, with reciprocal suppression of the stimulatory PTP1B/Syk axis, thus potently inhibiting anaphylaxis. Overall, our results provide a molecular explanation for the beneficial role of Sirt1 in allergy and underscore a potential application of Sirt1 activators as a new class of anti-allergic agents.

SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to EGF stimulation

International Nuclear Information System (INIS)

Huang Lin; Gotoh, Noriko; Zhang Shengliang; Shibuya, Masabumi; Yamamoto, Tadashi; Tsuchida, Nobuo

2004-01-01

The control of cellular responses with fibroblast growth factors and neurotrophins is mediated through membrane-linked docking proteins, SNT (suc1-binding neurotrophic target)-1/FRS2α and SNT-2/FRS2β. ERK1/2 are members of the mitogen-activated protein kinase family that regulate diverse cellular activities in response to various stimuli. Here, we demonstrate that SNT-2 does not become tyrosine phosphorylated significantly in response to EGF but forms a complex with ERK2 via the region of 186-252 amino acid residues, and the complex formation is enhanced upon EGF stimulation. SNT-2 downregulates ERK2 phosphorylation, suppresses and delays ERK2 nuclear accumulation which occurs following EGF stimulation. In contrast, the mutant SNT-2 which carries deletion of 186-252 amino acids and lacks ERK2 binding does not have these effects. These observations suggest that SNT-2 negatively regulates ERK2 signaling activated via EGF stimulation through direct binding to ERK2

Regulative environmental policy. Regulative Umweltpolitik

Energy Technology Data Exchange (ETDEWEB)

Goerlitz, A; Voigt, R [Universitaet der Bundeswehr Muenchen, Neubiberg (Germany, F.R.). Fakultaet fuer Sozialwissenschaften; eds.

1991-01-01

Regulative policy means those governmental attempts to steer the course of things which can fall back on a certain repertoire of instruments for actions in order to warrant the causal and temporal connection between the making available and the employment of means. The fact that environmental protection needs regulative policy is substantiated by the thesis that the market has failed; consequently only government can manage the public goods 'environment' in a suitable way, and it is a matter of fact that environmental protection at present is operated preferably via regulative policy. The problems of regulative enviromental policy are manifold. Its implementation often miscarries because of limited administrative resources on the one hand - making sufficient control impossible for instance -, and because of poor quality regulative instruments on the other hand. One way out would be to increase the efficiency of regulative policy by sophisticating judicial techniques. Other ways out point to the executing level and aim at improving implementation strategies or are concerned with post-regulative law. The latter refers to a new legal quality which demonstrates itself already in corporatistical crisis regulation or in induction programs such as pollution limits. A final way out favours deregulation strategies which includes the introduction of environmental levies or the allocation of environmental licences. An interdisciplinary discourse is to find out what would happen if these ways were taken. Pointers to solutions from varying scientific disciplines resulting from this discourse are to be found in this volume. (orig./HSCH).

Tomato NAC transcription factor SlSRN1 positively regulates defense response against biotic stress but negatively regulates abiotic stress response.

Directory of Open Access Journals (Sweden)

Bo Liu

Full Text Available Biotic and abiotic stresses are major unfavorable factors that affect crop productivity worldwide. NAC proteins comprise a large family of transcription factors that play important roles in plant growth and development as well as in responses to biotic and abiotic stresses. In a virus-induced gene silencing-based screening to identify genes that are involved in defense response against Botrytis cinerea, we identified a tomato NAC gene SlSRN1 (Solanum lycopersicum Stress-related NAC1. SlSRN1 is a plasma membrane-localized protein with transactivation activity in yeast. Expression of SlSRN1 was significantly induced by infection with B. cinerea or Pseudomonas syringae pv. tomato (Pst DC3000, leading to 6-8 folds higher than that in the mock-inoculated plants. Expression of SlSRN1 was also induced by salicylic acid, jasmonic acid and 1-amino cyclopropane-1-carboxylic acid and by drought stress. Silencing of SlSRN1 resulted in increased severity of diseases caused by B. cinerea and Pst DC3000. However, silencing of SlSRN1 resulted in increased tolerance against oxidative and drought stresses. Furthermore, silencing of SlSRN1 accelerated accumulation of reactive oxygen species but attenuated expression of defense genes after infection by B. cinerea. Our results demonstrate that SlSRN1 is a positive regulator of defense response against B. cinerea and Pst DC3000 but is a negative regulator for oxidative and drought stress response in tomato.

Suppressor of Overexpression of CO 1 Negatively Regulates Dark-Induced Leaf Degreening and Senescence by Directly Repressing Pheophytinase and Other Senescence-Associated Genes in Arabidopsis.

Science.gov (United States)

Chen, Junyi; Zhu, Xiaoyu; Ren, Jun; Qiu, Kai; Li, Zhongpeng; Xie, Zuokun; Gao, Jiong; Zhou, Xin; Kuai, Benke

2017-03-01

Although the biochemical pathway of chlorophyll (Chl) degradation has been largely elucidated, how Chl is rapidly yet coordinately degraded during leaf senescence remains elusive. Pheophytinase (PPH) is the enzyme for catalyzing the removal of the phytol group from pheophytin a , and PPH expression is significantly induced during leaf senescence. To elucidate the transcriptional regulation of PPH , we used a yeast ( Saccharomyces cerevisiae ) one-hybrid system to screen for its trans-regulators. SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1), a key flowering pathway integrator, was initially identified as one of the putative trans-regulators of PPH After dark treatment, leaves of an SOC1 knockdown mutant ( soc1-6 ) showed an accelerated yellowing phenotype, whereas those of SOC1 -overexpressing lines exhibited a partial stay-green phenotype. SOC1 and PPH expression showed a negative correlation during leaf senescence. Substantially, SOC1 protein could bind specifically to the CArG box of the PPH promoter in vitro and in vivo, and overexpression of SOC1 significantly inhibited the transcriptional activity of the PPH promoter in Arabidopsis ( Arabidopsis thaliana ) protoplasts. Importantly, soc1-6 pph-1 (a PPH knockout mutant) double mutant displayed a stay-green phenotype similar to that of pph-1 during dark treatment. These results demonstrated that SOC1 inhibits Chl degradation via negatively regulating PPH expression. In addition, measurement of the Chl content and the maximum photochemical efficiency of photosystem II of soc1-6 and SOC1-OE leaves after dark treatment suggested that SOC1 also negatively regulates the general senescence process. Seven SENESCENCE-ASSOCIATED GENES ( SAGs ) were thereafter identified as its potential target genes, and NONYELLOWING1 and SAG113 were experimentally confirmed. Together, we reveal that SOC1 represses dark-induced leaf Chl degradation and senescence in general in Arabidopsis. © 2017 American Society of Plant Biologists. All

‘Fortress Europe’: Compliance of the Dublin II Regulation with the European Convention for the Protection of Human Rights and Fundamental Freedoms

Directory of Open Access Journals (Sweden)

Joanna Lenart

2012-06-01

Full Text Available Recently, the Dublin II Regulation, a cornerstone of the emerging Common European Asylum System, has been gravely criticised, especially in context of the living conditions and general situation of asylum seekers in Greece. The main concerns regard the potential noncompliance of the Dublin II Regulation with the European Convention on Human Rights ('ECHR', particularly with Article 3 - the prohibition of torture or inhuman or degrading treatment. This article examines the competing views in this respect. It analyses the relationship between EU law and the ECHR, protection of rights of refugees under the 1951 Convention relating to the Status of Refugees and main deficiencies of the Dublin II Regulation. The analysis starts with the non-equivalent protection of asylum seekers throughout the EU and finishes with the very limited definition of a family member and case law relevant to the principle of non-refoulement. This article concludes that the Dublin II Regulation per se cannot be deemed noncompliant with the ECHR. However, it emphasises the urgent need to change relevant legal provisions, or at least enforcement, and proposes possible solutions therein.

The C-terminal domain of Nrf1 negatively regulates the full-length CNC-bZIP factor and its shorter isoform LCR-F1/Nrf1β; both are also inhibited by the small dominant-negative Nrf1γ/δ isoforms that down-regulate ARE-battery gene expression.

Science.gov (United States)

Zhang, Yiguo; Qiu, Lu; Li, Shaojun; Xiang, Yuancai; Chen, Jiayu; Ren, Yonggang

2014-01-01

The C-terminal domain (CTD, aa 686-741) of nuclear factor-erythroid 2 p45-related factor 1 (Nrf1) shares 53% amino acid sequence identity with the equivalent Neh3 domain of Nrf2, a homologous transcription factor. The Neh3 positively regulates Nrf2, but whether the Neh3-like (Neh3L) CTD of Nrf1 has a similar role in regulating Nrf1-target gene expression is unknown. Herein, we report that CTD negatively regulates the full-length Nrf1 (i.e. 120-kDa glycoprotein and 95-kDa deglycoprotein) and its shorter isoform LCR-F1/Nrf1β (55-kDa). Attachment of its CTD-adjoining 112-aa to the C-terminus of Nrf2 yields the chimaeric Nrf2-C112Nrf1 factor with a markedly decreased activity. Live-cell imaging of GFP-CTD reveals that the extra-nuclear portion of the fusion protein is allowed to associate with the endoplasmic reticulum (ER) membrane through the amphipathic Neh3L region of Nrf1 and its basic c-tail. Thus removal of either the entire CTD or the essential Neh3L portion within CTD from Nrf1, LCR-F1/Nrf1β and Nrf2-C112Nrf1, results in an increase in their transcriptional ability to regulate antioxidant response element (ARE)-driven reporter genes. Further examinations unravel that two smaller isoforms, 36-kDa Nrf1γ and 25-kDa Nrf1δ, act as dominant-negative inhibitors to compete against Nrf1, LCR-F1/Nrf1β and Nrf2. Relative to Nrf1, LCR-F1/Nrf1β is a weak activator, that is positively regulated by its Asn/Ser/Thr-rich (NST) domain and acidic domain 2 (AD2). Like AD1 of Nrf1, both AD2 and NST domain of LCR-F1/Nrf1β fused within two different chimaeric contexts to yield Gal4D:Nrf1β607 and Nrf1β:C270Nrf2, positively regulate their transactivation activity of cognate Gal4- and Nrf2-target reporter genes. More importantly, differential expression of endogenous ARE-battery genes is attributable to up-regulation by Nrf1 and LCR-F1/Nrf1β and down-regulation by Nrf1γ and Nrf1δ.

Sildenafil protects against bile duct ligation induced hepatic fibrosis in rats: Potential role for silent information regulator 1 (SIRT1).

Science.gov (United States)

Abd El Motteleb, Dalia M; Ibrahim, Islam A A E-H; Elshazly, Shimaa M

2017-11-15

Hepatic fibrosis is a potential health problem that may end with life-threatening cirrhosis and primary liver cancer. Recent studies point out to the protective effects of silent information regulator1 (SIRT1), against different models of organs fibrosis. This work aimed to investigate the possible protective effect of sildenafil (SIRT1 activator) against hepatic fibrosis induced by bile duct ligation (BDL). Firstly, three different doses of sildenafil (5, 10, 20mg/kg/day) were investigated; to detect the most protective one against BDL induced liver dysfunction and hepatic fibrosis. The most protective dose is then used; to study its effect on BDL induced SIRT1 downregulation, imbalance of oxidant/antioxidant status, increased inflammatory cytokines and fibrosis. Sildenafil (20mg/kg/day) was the most protective one, it caused upregulation of SIRT1, reduction of hepatic malondialdehyde (MDA) content, increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenease (HO)-1, reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Hepatic content of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NFκB) expression & content displayed significant reductions with sildenafil treatment, Furthermore, sildenafil caused marked reductions of transforming growth factor (TGF)-β content, expression of plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), α-smooth muscle actin (α-SMA), fibronectin, collagen I (α1) and hydroxyproline content. However, sildenafil protective effects were significantly reduced by co-administration of EX527 (SIRT1 inhibitor). Our work showed, for the first time that, sildenafil has promising protective effects against BDL induced liver dysfunction and hepatic fibrosis. These effects may be, in part, mediated by up regulation of SIRT1. Copyright © 2017. Published by Elsevier Inc.

A negative regulator encoded by a rice WRKY gene represses both abscisic acid and gibberellins signaling in aleurone cells.

Science.gov (United States)

Zhang, Zhong-Lin; Shin, Margaret; Zou, Xiaolu; Huang, Jianzhi; Ho, Tun-hua David; Shen, Qingxi J

2009-05-01

Abscisic acid (ABA) and gibberellins (GAs) control several developmental processes including seed maturation, dormancy, and germination. The antagonism of these two hormones is well-documented. However, recent data from transcription profiling studies indicate that they can function as agonists in regulating the expression of many genes although the underlying mechanism is unclear. Here we report a rice WRKY gene, OsWRKY24, which encodes a protein that functions as a negative regulator of both GA and ABA signaling. Overexpression of OsWRKY24 via particle bombardment-mediated transient expression in aleurone cells represses the expression of two reporter constructs: the beta-glucuronidase gene driven by the GA-inducible Amy32b alpha-amylase promoter (Amy32b-GUS) and the ABA-inducible HVA22 promoter (HVA22-GUS). OsWRKY24 is unlikely a general repressor because it has little effect on the expression of the luciferase reporter gene driven by a constitutive ubiquitin promoter (UBI-Luciferase). As to the GA signaling, OsWRKY24 differs from OsWRKY51 and -71, two negative regulators specifically function in the GA signaling pathway, in several ways. First, OsWRKY24 contains two WRKY domains while OsWRKY51 and -71 have only one; both WRKY domains are essential for the full repressing activity of OsWRKY24. Second, binding of OsWRKY24 to the Amy32b promoter appears to involve sequences in addition to the TGAC cores of the W-boxes. Third, unlike OsWRKY71, OsWRKY24 is stable upon GA treatment. Together, these data demonstrate that OsWRKY24 is a novel type of transcriptional repressor that inhibits both GA and ABA signaling.

HOW SHOULD THE WELFARE OF FETAL AND NEUROLOGICALLY IMMATURE POSTNATAL ANIMALS BE PROTECTED?

Science.gov (United States)

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

Off-road compression-ignition engine emission regulations under the Canadian Environmental Protection Act 1999 : guidance document

International Nuclear Information System (INIS)

2006-03-01

This guide explained the requirements for Off-Road Compression Ignition Engine Emission Regulations established under the Canadian Environmental Protection Act. The regulations are enforced by Environment Canada, which authorizes and monitors the use of the national emissions mark. The regulations prescribe standards for off-road engines that operate as reciprocating, internal combustion engines, other than those that operate under characteristics similar to the Otto combustion cycle and that use a spark plug or other sparking device. The regulations apply to engines that are typically diesel-fuelled and found in construction, mining, farming and forestry machines such as tractors, excavators and log skidders. Four different types of persons are potentially affected by the regulations: Canadian engine manufacturers; distributors of Canadian engines or machines containing Canadian engines; importers of engines or machines for the purpose of sale; and persons not in companies importing engines or machines. Details of emission standards were presented, as well as issues concerning evidence of conformity, importing engines, and special engine cases. Compliance and enforcement details were reviewed, as well as applicable standards and provisions for emission control systems and defeat devices; exhaust emissions; crankcase and smoke emissions; and adjustable parameters. Details of import declarations were reviewed, as well as issues concerning defects and maintenance instructions. 4 tabs., 4 figs

VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle.

Science.gov (United States)

Cantarero, Lara; Sanz-García, Marta; Vinograd-Byk, Hadar; Renbaum, Paul; Levy-Lahad, Ephrat; Lazo, Pedro A

2015-06-12

Cajal bodies (CBs) are nuclear organelles associated with ribonucleoprotein functions and RNA maturation. CBs are assembled on coilin, its main scaffold protein, in a cell cycle dependent manner. The Ser-Thr VRK1 (vaccinia-related kinase 1) kinase, whose activity is also cell cycle regulated, interacts with and phosphorylates coilin regulating assembly of CBs. Coilin phosphorylation is not necessary for its interaction with VRK1, but it occurs in mitosis and regulates coilin stability. Knockdown of VRK1 or VRK1 inactivation by serum deprivation causes a loss of coilin phosphorylation in Ser184 and of CBs formation, which are rescued with an active VRK1, but not by kinase-dead VRK1. The phosphorylation of coilin in Ser184 occurs during mitosis before assembly of CBs. Loss of coilin phosphorylation results in disintegration of CBs, and of coilin degradation that is prevented by proteasome inhibitors. After depletion of VRK1, coilin is ubiquitinated in nuclei, which is partly mediated by mdm2, but its proteasomal degradation occurs in cytosol and is prevented by blocking its nuclear export. We conclude that VRK1 is a novel regulator of CBs dynamics and stability in cell cycle by protecting coilin from ubiquitination and degradation in the proteasome, and propose a model of CB dynamics.

Design and Evaluation of a Protection Relay for a Wind Generator Based on the Positive- and Negative-Sequence Fault Components

DEFF Research Database (Denmark)

Zheng, T. Y.; Cha, Seung-Tae; Crossley, P. A.

2013-01-01

To avoid undesirable disconnection of healthy wind generators (WGs) or a wind power plant, a WG protection relay should discriminate among faults, so that it can operate instantaneously for WG, connected feeder or connection bus faults, it can operate after a delay for inter-tie or grid faults......, and it can avoid operating for parallel WG or adjacent feeder faults. A WG protection relay based on the positive- and negativesequence fault components is proposed in the paper. At stage 1, the proposed relay uses the magnitude of the positive-sequence component in the fault current to distinguish faults...... at a parallel WG connected to the same feeder or at an adjacent feeder, from other faults at a connected feeder, an inter-tie, or a grid. At stage 2, the fault type is first determined using the relationships between the positive- and negative-sequence fault components. Then, the relay differentiates between...

To Regulate or Not to Regulate? Views on Electronic Cigarette Regulations and Beliefs about the Reasons for and against Regulation.

Science.gov (United States)

Sanders-Jackson, Ashley; Tan, Andy S L; Bigman, Cabral A; Mello, Susan; Niederdeppe, Jeff

2016-01-01

Policies designed to restrict marketing, access to, and public use of electronic cigarettes (e-cigarettes) are increasingly under debate in various jurisdictions in the US. Little is known about public perceptions of these policies and factors that predict their support or opposition. Using a sample of US adults from Amazon Mechanical Turk in May 2015, this paper identifies beliefs about the benefits and costs of regulating e-cigarettes and identifies which of these beliefs predict support for e-cigarette restricting policies. A higher proportion of respondents agreed with 8 different reasons to regulate e-cigarettes (48.5% to 83.3% agreement) versus 7 reasons not to regulate e-cigarettes (11.5% to 18.9%). The majority of participants agreed with 7 out of 8 reasons for regulation. When all reasons to regulate or not were included in a final multivariable model, beliefs about protecting people from secondhand vapor and protecting youth from trying e-cigarettes significantly predicted stronger support for e-cigarette restricting policies, whereas concern about government intrusion into individual choices was associated with reduced support. This research identifies key beliefs that may underlie public support or opposition to policies designed to regulate the marketing and use of e-cigarettes. Advocates on both sides of the issue may find this research valuable in developing strategic campaigns related to the issue. Specific beliefs of potential benefits and costs of e-cigarette regulation (protecting youth, preventing exposure to secondhand vapor, and government intrusion into individual choices) may be effectively deployed by policy makers or health advocates in communicating with the public.

To Regulate or Not to Regulate? Views on Electronic Cigarette Regulations and Beliefs about the Reasons for and against Regulation.

Directory of Open Access Journals (Sweden)

Ashley Sanders-Jackson

Full Text Available Policies designed to restrict marketing, access to, and public use of electronic cigarettes (e-cigarettes are increasingly under debate in various jurisdictions in the US. Little is known about public perceptions of these policies and factors that predict their support or opposition.Using a sample of US adults from Amazon Mechanical Turk in May 2015, this paper identifies beliefs about the benefits and costs of regulating e-cigarettes and identifies which of these beliefs predict support for e-cigarette restricting policies.A higher proportion of respondents agreed with 8 different reasons to regulate e-cigarettes (48.5% to 83.3% agreement versus 7 reasons not to regulate e-cigarettes (11.5% to 18.9%. The majority of participants agreed with 7 out of 8 reasons for regulation. When all reasons to regulate or not were included in a final multivariable model, beliefs about protecting people from secondhand vapor and protecting youth from trying e-cigarettes significantly predicted stronger support for e-cigarette restricting policies, whereas concern about government intrusion into individual choices was associated with reduced support.This research identifies key beliefs that may underlie public support or opposition to policies designed to regulate the marketing and use of e-cigarettes. Advocates on both sides of the issue may find this research valuable in developing strategic campaigns related to the issue.Specific beliefs of potential benefits and costs of e-cigarette regulation (protecting youth, preventing exposure to secondhand vapor, and government intrusion into individual choices may be effectively deployed by policy makers or health advocates in communicating with the public.

Radiation protection at workplaces with increased natural radiation exposure in Greece: recording, monitoring and protection measures

International Nuclear Information System (INIS)

Potiriadis, C.; Koukoliou, V.

2002-01-01

Greek Atomic Energy Commission (GAEC) is the regulatory, advisory and competent authority on radiation protection matters. It is the authority responsible for the introduction of Radiation Protection regulations and monitoring of their implementation. In 1997, within the frame of its responsibilities the Board of the GAEC appointed a task group of experts to revise and bring the present Radiation Protection Regulations into line with the Basic Safety Standards (BSS) 96/29/Euratom Directive and the 97/43/Euratom Directive (on health protection of individuals against the dangers of ionising radiation in relation to medical exposure). Concerning the Title 7. of the new European BSS Directive, which refers to the Radiation Protection at work places with increased levels of natural radiation exposure, the Radiation Protection Regulations provides that the authority responsible for recording, monitoring and introducing protection measures at these places is the GAEC. Practices where effective doses to the workers due to increased natural radiation levels, may exceed 1mSv/y, have to be specified and authorised by the GAEC. The identification procedure is ongoing

Radiation protection in Qatar

International Nuclear Information System (INIS)

Al Maadheed, Khalid; Al Khatibeh, Ahmad

2008-01-01

Full text: The State of Qatar has become a member State of IAEA since 1974. Later the Department of Industrial Development (DID) beam the focal point and the competent authority regarding all aspects of the peaceful application of Nuclear Technology. In July, 2000 the Supreme Council was established and charged with all matters related to environmental protection. The Supreme Council joined the IAEA Projects on upgrading protection infrastructure in West Asia region. A preliminary research was initiated to discover where radiation sources are being used, and the legal framework, if any, to regulate their use. The research indicated that radiation sources were being used in the industrial practices (well logging, industrial radiography and nuclear gauges) and in medical practices (mainly diagnostic radiology). The research also indicated that there was virtually no legal framework to regulate them. In less than five years, the State of Qatar was able to issue the radiation protection law, three sets of regulations, namely: Radiation Protection Regulations, Radioactive Waste Management Regulations and the Safe Transport of Radioactive Materials Regulations. In addition, several specific regulation work, dose limits and radiation protection officers were issued. A radiation Protection Department, comprising three sections was established. We are providing individual exposure monitoring for most of the radiation workers in the public sector and some in the private sector. We have set up a proper licensing and inspections procedures, where our inspectors are enforcing the law. More recently, we established an early warning network for nuclear of radiological emergencies, consisting of 6 transplantable stations, five mobile stations and two navigating stations. This year, the network was augmented with five fixed station and an advanced early warning centre, which provides early warning via multiple means (MMS, Fax, E-mail and audio alarms). Last year we signed a nuclear

Phytochrome-interacting factors PIF4 and PIF5 negatively regulate anthocyanin biosynthesis under red light in Arabidopsis seedlings.

Science.gov (United States)

Liu, Zhongjuan; Zhang, Yongqiang; Wang, Jianfeng; Li, Ping; Zhao, Chengzhou; Chen, Yadi; Bi, Yurong

2015-09-01

Light is an important environmental factor inducing anthocyanin accumulation in plants. Phytochrome-interacting factors (PIFs) have been shown to be a family of bHLH transcription factors involved in light signaling in Arabidopsis. Red light effectively increased anthocyanin accumulation in wild-type Col-0, whereas the effects were enhanced in pif4 and pif5 mutants but impaired in overexpression lines PIF4OX and PIF5OX, indicating that PIF4 and PIF5 are both negative regulators for red light-induced anthocyanin accumulation. Consistently, transcript levels of several genes involved in anthocyanin biosynthesis and regulatory pathway, including CHS, F3'H, DFR, LDOX, PAP1 and TT8, were significantly enhanced in mutants pif4 and pif5 but decreased in PIF4OX and PIF5OX compared to in Col-0, indicating that PIF4 and PIF5 are transcriptional repressor of these gene. Transient expression assays revealed that PIF4 and PIF5 could repress red light-induced promoter activities of F3'H and DFR in Arabidopsis protoplasts. Furthermore, chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) test and electrophoretic mobility shift assay (EMSA) showed that PIF5 could directly bind to G-box motifs present in the promoter of DFR. Taken together, these results suggest that PIF4 and PIF5 negatively regulate red light-induced anthocyanin accumulation through transcriptional repression of the anthocyanin biosynthetic genes in Arabidopsis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Industry participation in the development of a risk-informed, performance-based regulation for fire protection at US nuclear power plants

International Nuclear Information System (INIS)

Emerson, F.A.

1998-01-01

The USNRC staff have recently been directed by the NRC Commissioners to evaluate quickly the development of a risk-informed, performance-based fire protection regulation to replace the current regulations. The US nuclear industry does not believe a new rule is necessary to increase fire safety, and believes that there are significant risks and potentially significant benefits depending on the construction of the rule. However, the industry will actively work with NRC staff if rulemaking proceeds such that the risks are minimized and the benefits maximized. A Nuclear Energy Institute (NEI) Issue Task Force (ITF) has been established to guide the participation of industry in any rulemaking activity. If rulemaking proceeds, a framework should be established for the evolution of a fire protection rule from the current prescriptive basis to a risk-informed, performance-based rule. (author)

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

Science.gov (United States)

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

2016-02-01

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

47 CFR 76.981 - Negative option billing.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Negative option billing. 76.981 Section 76.981 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cable Rate Regulation § 76.981 Negative option billing. (a) A cable operator...

Protection and control of nuclear materials

International Nuclear Information System (INIS)

Jalouneix, J.; Winter, D.

2007-01-01

In the framework of the French regulation on nuclear materials possession, the first liability is the one of operators who have to know at any time the quantity, quality and localization of any nuclear material in their possession. This requires an organization of the follow up and of the inventory of these materials together with an efficient protection against theft or sabotage. The French organization foresees a control of the implementation of this regulation at nuclear facilities and during the transport of nuclear materials by the minister of industry with the sustain of the institute of radiation protection and nuclear safety (IRSN). This article presents this organization: 1 - protection against malevolence; 2 - national protection and control of nuclear materials: goals, administrative organization, legal and regulatory content (authorization, control, sanctions), nuclear materials protection inside facilities (physical protection, follow up and inventory, security studies), protection of nuclear material transports (physical protection, follow up), control of nuclear materials (inspection at facilities, control of nuclear material measurements, inspection of nuclear materials during transport); 3 - international commitments of France: non-proliferation treaty, EURATOM regulation, international convention on the physical protection of nuclear materials, enforcement in France. (J.S.)

Resolvin D1 Protects Lipopolysaccharide-induced Acute Kidney Injury by Down-regulating Nuclear Factor-kappa B Signal and Inhibiting Apoptosis

Directory of Open Access Journals (Sweden)

Yu-Liang Zhao

2016-01-01

Conclusion: In LPS-induced AKI, RvD1 could decrease TNF-α level, ameliorate kidney pathological injury, protect kidney function, and improve animal survival by down-regulating NF-κB inflammatory signal as well as inhibiting renal cell apoptosis.

3084 ROYAL DECREE No 53/1992 of 24 January 1992 approving the Regulation on Health Protection against Ionizing Radiation

International Nuclear Information System (INIS)

1992-01-01

The purpose of this new Regulation is to unite in a single instrument the existing rules on this subject contained in Decree 2519/1982 as amended by Decree 1753/1987, now repealed, as well as to introduce certain modifications which have proved desirable in the light of the practical application of those rules. The 1987 Decree reflected the basic safety standards of the Euratom Directives. Like that Decree, the new regulation lays down the measures for protection of the public and occupationally exposed persons against the dangers of ionizing radiation. The Regulation is supplemented by Appendices providing for definitions of radiological, biological and medical terms, annual dose limits for the public and for occupationally exposed persons, etc. (NEA)

Cytoprotective effect exerted by geraniin in HepG2 cells is through microRNA mediated regulation of BACH-1 and HO-1.

Science.gov (United States)

Aayadi, Hoda; Mittal, Smriti P K; Deshpande, Anjali; Gore, Makarand; Ghaskadbi, Saroj S

2017-11-01

Geraniin, a hydrolysable tannin, used in traditional medicine in Southeast Asia, is known to exhibit various biological activities. As an antioxidant it is known to up-regulate phase II enzyme Heme oxygenase-1 (HO-1). However its mechanism is not clearly understood. Nuclear factor erythroid-derived 2 related factor 2 (Nrf-2) is transcriptionally up-regulated by Extracellular signal-regulated kinase (ERK) 1/2 and retained in nucleus due to inactivated Glycogen synthase kinase 3 beta (GSK-3β). Geraniin additionally down-regulates expression of microRNA 217 and 377 (miR-217 and miR-377) which target HO-1 mRNA. Expression of BTB and CNC homolog 1 (BACH-1), another regulator of HO-1, is also down-regulated by up-regulating microRNA 98 (miR-98), a negative regulator of BACH-1. Thus, geraniin up-regulates HO-1 expression both through activating its positive regulator Nrf-2 and by down-regulating its negative regulator BACH-1. Up-regulation of HO-1 also confers protection to HepG2 cells from tertiary butyl hydroperoxide (TBH) induced cytotoxicity. [BMB Reports 2017; 50(11): 560-565].

7 CFR 996.11 - Negative aflatoxin content.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Negative aflatoxin content. 996.11 Section 996.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... aflatoxin content. Negative aflatoxin content means 15 parts per billion (ppb) or less for peanuts that have...

Elaboration, publication and implementation of a technical regulation of radiological protection at the State of Sao Paulo

International Nuclear Information System (INIS)

Aldred, Martha Aurelia; Eduardo, Maria Bernardete de Paula

1996-01-01

Technological improvements of new equipment and some new topics of the international recommendations from ICRP 60 (1990) are considered in a meeting of radiation protection experts and representatives of professionals involved with the use of ionizing radiation in health care services. As a result a new regulation is proposed to the Sao Paulo State Health Department (Brazil). The importance of performing a quality assurance program is emphasized

Neural correlates of preparatory and regulatory control over positive and negative emotion.

Science.gov (United States)

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.

Protease-activated receptor-1 negatively regulates proliferation of neural stem/progenitor cells derived from the hippocampal dentate gyrus of the adult mouse

Directory of Open Access Journals (Sweden)

Masayuki Tanaka

2016-07-01

Full Text Available Thrombin-activated protease-activated receptor (PAR-1 regulates the proliferation of neural cells following brain injury. To elucidate the involvement of PAR-1 in the neurogenesis that occurs in the adult hippocampus, we examined whether PAR-1 regulated the proliferation of neural stem/progenitor cells (NPCs derived from the murine hippocampal dentate gyrus. NPC cultures expressed PAR-1 protein and mRNA encoding all subtypes of PAR. Direct exposure of the cells to thrombin dramatically attenuated the cell proliferation without causing cell damage. This thrombin-induced attenuation was almost completely abolished by the PAR antagonist RWJ 56110, as well as by dabigatran and 4-(2-aminoethylbenzenesulfonyl fluoride (AEBSF, which are selective and non-selective thrombin inhibitors, respectively. Expectedly, the PAR-1 agonist peptide (AP SFLLR-NH2 also attenuated the cell proliferation. The cell proliferation was not affected by the PAR-1 negative control peptide RLLFT-NH2, which is an inactive peptide for PAR-1. Independently, we determined the effect of in vivo treatment with AEBSF or AP on hippocampal neurogenesis in the adult mouse. The administration of AEBSF, but not that of AP, significantly increased the number of newly-generated cells in the hippocampal subgranular zone. These data suggest that PAR-1 negatively regulated adult neurogenesis in the hippocampus by inhibiting the proliferative activity of the NPCs.

The Impact of Regulating Social Science Research with Biomedical Regulations

Science.gov (United States)

Durosinmi, Brenda Braxton

2011-01-01

The Impact of Regulating Social Science Research with Biomedical Regulations Since 1974 Federal regulations have governed the use of human subjects in biomedical and social science research. The regulations are known as the Federal Policy for the Protection of Human Subjects, and often referred to as the "Common Rule" because 18 Federal…

Chrysanthemum WRKY gene CmWRKY17 negatively regulates salt stress tolerance in transgenic chrysanthemum and Arabidopsis plants.

Science.gov (United States)

Li, Peiling; Song, Aiping; Gao, Chunyan; Wang, Linxiao; Wang, Yinjie; Sun, Jing; Jiang, Jiafu; Chen, Fadi; Chen, Sumei

2015-08-01

CmWRKY17 was induced by salinity in chrysanthemum, and it might negatively regulate salt stress in transgenic plants as a transcriptional repressor. WRKY transcription factors play roles as positive or negative regulators in response to various stresses in plants. In this study, CmWRKY17 was isolated from chrysanthemum (Chrysanthemum morifolium). The gene encodes a 227-amino acid protein and belongs to the group II WRKY family, but has an atypical WRKY domain with the sequence WKKYGEK. Our data indicated that CmWRKY17 was localized to the nucleus in onion epidermal cells. CmWRKY17 showed no transcriptional activation in yeast; furthermore, luminescence assay clearly suggested that CmWRKY17 functions as a transcriptional repressor. DNA-binding assay showed that CmWRKY17 can bind to W-box. The expression of CmWRKY17 was induced by salinity in chrysanthemum, and a higher expression level was observed in the stem and leaf compared with that in the root, disk florets, and ray florets. Overexpression of CmWRKY17 in chrysanthemum and Arabidopsis increased the sensitivity to salinity stress. The activities of superoxide dismutase and peroxidase and proline content in the leaf were significantly lower in transgenic chrysanthemum than those in the wild type under salinity stress, whereas electrical conductivity was increased in transgenic plants. Expression of the stress-related genes AtRD29, AtDREB2B, AtSOS1, AtSOS2, AtSOS3, and AtNHX1 was reduced in the CmWRKY17 transgenic Arabidopsis compared with that in the wild-type Col-0. Collectively, these data suggest that CmWRKY17 may increase the salinity sensitivity in plants as a transcriptional repressor.

Assumptions used in determining the radiation exposure according to the amended Radiation Protection Ordinance, and required adjustments in the General Administrative Regulation relating to paragraph 45 of the Radiation Protection Ordinance

International Nuclear Information System (INIS)

Wirth, E.

2000-01-01

Within the framework of the amendment of the Radiation Protection Ordinance, the need arises to also amend the General Administrative Regulation on calculation of the radiation exposure due to radioactivity release with gaseous or liquid effluents, for the purpose of verification of compliance with the dose limits given in section 45 of the Radiation Protection Ordinance. The General Administrative regulation has to be harmonized with European legislation, EURATOM Directive 96/29. The required consultations for decision making have been a task of the working group for 'Anpassung der radiooekologischen Berechnungsgrundlage', of the Radioecology Committee of the SSK. The paper discusses the resulting draft document for amendment presented to and accepted by the SSK Committee. The document is awaiting discussion for final decision among members of the SSK, and between the SSK and representatives of Land governments as well as various bodies representing interests. (orig./CB) [de

Canonical TGF-β Signaling Negatively Regulates Neuronal Morphogenesis through TGIF/Smad Complex-Mediated CRMP2 Suppression.

Science.gov (United States)

Nakashima, Hideyuki; Tsujimura, Keita; Irie, Koichiro; Ishizu, Masataka; Pan, Miao; Kameda, Tomonori; Nakashima, Kinichi

2018-05-16

Functional neuronal connectivity requires proper neuronal morphogenesis and its dysregulation causes neurodevelopmental diseases. Transforming growth factor-β (TGF-β) family cytokines play pivotal roles in development, but little is known about their contribution to morphological development of neurons. Here we show that the Smad-dependent canonical signaling of TGF-β family cytokines negatively regulates neuronal morphogenesis during brain development. Mechanistically, activated Smads form a complex with transcriptional repressor TG-interacting factor (TGIF), and downregulate the expression of a neuronal polarity regulator, collapsin response mediator protein 2. We also demonstrate that TGF-β family signaling inhibits neurite elongation of human induced pluripotent stem cell-derived neurons. Furthermore, the expression of TGF-β receptor 1, Smad4, or TGIF, which have mutations found in patients with neurodevelopmental disorders, disrupted neuronal morphogenesis in both mouse (male and female) and human (female) neurons. Together, these findings suggest that the regulation of neuronal morphogenesis by an evolutionarily conserved function of TGF-β signaling is involved in the pathogenesis of neurodevelopmental diseases. SIGNIFICANCE STATEMENT Canonical transforming growth factor-β (TGF-β) signaling plays a crucial role in multiple organ development, including brain, and mutations in components of the signaling pathway associated with several human developmental disorders. In this study, we found that Smads/TG-interacting factor-dependent canonical TGF-β signaling regulates neuronal morphogenesis through the suppression of collapsin response mediator protein-2 (CRMP2) expression during brain development, and that function of this signaling is evolutionarily conserved in the mammalian brain. Mutations in canonical TGF-β signaling factors identified in patients with neurodevelopmental disorders disrupt the morphological development of neurons. Thus, our

Criminal Protection of the Consumer of Irradiated food and Consumer Protection Against Contaminated Food with Radioactive Isotopes

International Nuclear Information System (INIS)

El-Baroudy, M.M.

2003-01-01

The widespread peaceful applications of atomic energy in food and agriculture had various positive and negative impacts on the economies of food and its production. Food is positively affected through either its treatment by ionizing radiation to preserve and reduce losses in it or by using mutations treated by ionizing radiation for improving their productivity. On the other hand, negative effects of nuclear energy on food are caused by nuclear explosions in nuclear weapons testing as well as by different nuclear energy applications and the wastes formed as a result of it. These activities can cause different contamination levels of the environment and particularly, the arable land. This in turn leads to the production of contaminated food with radioactive isotopes. Consequently, the present work which is subdivided into two parts, involves a study of both the positive and negative effects of ionizing radiations and radioactive isotopes on food. The first part deals with the legal protection of food treated by ionizing radiations to preserve it, explaining the related different legal and regulatory aspects. Food irradiation processes should be carried out in a framework of the national control regulations and in a way that is consistent with the reference standards adopted internationally for the safety and hygiene of food

Exercise Activates p53 and Negatively Regulates IGF-1 Pathway in Epidermis within a Skin Cancer Model.

Science.gov (United States)

Yu, Miao; King, Brenee; Ewert, Emily; Su, Xiaoyu; Mardiyati, Nur; Zhao, Zhihui; Wang, Weiqun

2016-01-01

Exercise has been previously reported to lower cancer risk through reducing circulating IGF-1 and IGF-1-dependent signaling in a mouse skin cancer model. This study aims to investigate the underlying mechanisms by which exercise may down-regulate the IGF-1 pathway via p53 and p53-related regulators in the skin epidermis. Female SENCAR mice were pair-fed an AIN-93 diet with or without 10-week treadmill exercise at 20 m/min, 60 min/day and 5 days/week. Animals were topically treated with TPA 2 hours before sacrifice and the target proteins in the epidermis were analyzed by both immunohistochemistry and Western blot. Under TPA or vehicle treatment, MDM2 expression was significantly reduced in exercised mice when compared with sedentary control. Meanwhile, p53 was significantly elevated. In addition, p53-transcriptioned proteins, i.e., p21, IGFBP-3, and PTEN, increased in response to exercise. There was a synergy effect between exercise and TPA on the decreased MDM2 and increased p53, but not p53-transcripted proteins. Taken together, exercise appeared to activate p53, resulting in enhanced expression of p21, IGFBP-3, and PTEN that might induce a negative regulation of IGF-1 pathway and thus contribute to the observed cancer prevention by exercise in this skin cancer model.

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

Science.gov (United States)

Luong, Gloria; Charles, Susan T.

2014-01-01

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

TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis.

Science.gov (United States)

Sun, Honghong; Gong, Shunyou; Carmody, Ruaidhri J; Hilliard, Anja; Li, Li; Sun, Jing; Kong, Li; Xu, Lingyun; Hilliard, Brendan; Hu, Shimin; Shen, Hao; Yang, Xiaolu; Chen, Youhai H

2008-05-02

Immune homeostasis is essential for the normal functioning of the immune system, and its breakdown leads to fatal inflammatory diseases. We report here the identification of a member of the tumor necrosis factor-alpha-induced protein-8 (TNFAIP8) family, designated TIPE2, that is required for maintaining immune homeostasis. TIPE2 is preferentially expressed in lymphoid tissues, and its deletion in mice leads to multiorgan inflammation, splenomegaly, and premature death. TIPE2-deficient animals are hypersensitive to septic shock, and TIPE2-deficient cells are hyper-responsive to Toll-like receptor (TLR) and T cell receptor (TCR) activation. Importantly, TIPE2 binds to caspase-8 and inhibits activating protein-1 and nuclear factor-kappaB activation while promoting Fas-induced apoptosis. Inhibiting caspase-8 significantly blocks the hyper-responsiveness of TIPE2-deficient cells. These results establish that TIPE2 is an essential negative regulator of TLR and TCR function, and its selective expression in the immune system prevents hyperresponsiveness and maintains immune homeostasis.

Ethanol negatively regulates hepatic differentiation of hESC by inhibition of the MAPK/ERK signaling pathway in vitro.

Directory of Open Access Journals (Sweden)

Wei Gao

Full Text Available Alcohol insult triggers complex events in the liver, promoting fibrogenic/inflammatory signals and in more advanced cases, aberrant matrix deposition. It is well accepted that the regenerative capacity of the adult liver is impaired during alcohol injury. The liver progenitor/stem cells have been shown to play an important role in liver regeneration -in response to various chronic injuries; however, the effects of alcohol on stem cell differentiation in the liver are not well understood.We employed hepatic progenitor cells derived from hESCs to study the impact of ethanol on hepatocyte differentiation by exposure of these progenitor cells to ethanol during hepatocyte differentiation.We found that ethanol negatively regulated hepatic differentiation of hESC-derived hepatic progenitor cells in a dose-dependent manner. There was also a moderate cell cycle arrest at G1/S checkpoint in the ethanol treated cells, which is associated with a reduced level of cyclin D1 in these cells. Ethanol treatment specifically inhibited the activation of the ERK but not JNK nor the p38 MAP signaling pathway. At the same time, the WNT signaling pathway was also reduced in the cells exposed to ethanol. Upon evaluating the effects of the inhibitors of these two signaling pathways, we determined that the Erk inhibitor replicated the effects of ethanol on the hepatocyte differentiation and attenuated the WNT/β-catenin signaling, however, inhibitors of WNT only partially replicated the effects of ethanol on the hepatocyte differentiation.Our results demonstrated that ethanol negatively regulated hepatic differentiation of hESC-derived hepatic progenitors through inhibiting the MAPK/ERK signaling pathway, and subsequently attenuating the WNT signaling pathway. Thus, our finding provides a novel insight into the mechanism by which alcohol regulates cell fate selection of hESC-derived hepatic progenitor cells, and the identified pathways may provide therapeutic targets

48{sup th} Annual meeting on nuclear technology (AMNT 2017). Key topic / Enhanced safety and operation excellence. Focus session: Radiation protection

Energy Technology Data Exchange (ETDEWEB)

Baumann, Erik [New NP GmbH, Erlangen (Germany); Bohnstedt, Angelika [Karlsruher Institut fuer Technologie (KIT), Eggenstein-Leopoldshafen (Germany). Programm Nukleare Entsorgung, Sicherheit und Strahlenforschung (NUSAFE)

2018-01-15

The objectives of radiation protection are to minimize the negative health effects due to radiation. Over many past decades, the regulatory environment, i.e. the various international and national codes and standards but also recommendations issued by IAEA and IRCP, was always subject to continuous development reflecting up to date knowledge and experience. Currently, discussions focus on ''new'' areas of human activities like decommissioning and on ''new radioactive substances'' and potential threats associated with their handling (handling and treatment of substances containing naturally occurring radioactive materials). Latter already became subject to regulations issued by EURATOM. For topics like decommissioning, statement can be found doubting that the existing regulations address radiation protection in a sufficient manner.

Arabidopsis ETO1 specifically interacts with and negatively regulates type 2 1-aminocyclopropane-1-carboxylate synthases

Directory of Open Access Journals (Sweden)

Saito Koji

2005-08-01

Full Text Available Abstract Background In Arabidopsis, ETO1 (ETHYLENE-OVERPRODUCER1 is a negative regulator of ethylene evolution by interacting with AtACS5, an isoform of the rate-limiting enzyme, 1-aminocyclopropane-1-carboxylate synthases (ACC synthase or ACS, in ethylene biosynthetic pathway. ETO1 directly inhibits the enzymatic activity of AtACS5. In addition, a specific interaction between ETO1 and AtCUL3, a constituent of a new type of E3 ubiquitin ligase complex, suggests the molecular mechanism in promoting AtACS5 degradation by the proteasome-dependent pathway. Because orthologous sequences to ETO1 are found in many plant species including tomato, we transformed tomato with Arabidopsis ETO1 to evaluate its ability to suppress ethylene production in tomato fruits. Results Transgenic tomato lines that overexpress Arabidopsis ETO1 (ETO1-OE did not show a significant delay of fruit ripening. So, we performed yeast two-hybrid assays to investigate potential heterologous interaction between ETO1 and three isozymes of ACC synthases from tomato. In the yeast two-hybrid system, ETO1 interacts with LE-ACS3 as well as AtACS5 but not with LE-ACS2 or LE-ACS4, two major isozymes whose gene expression is induced markedly in ripening fruits. According to the classification of ACC synthases, which is based on the C-terminal amino acid sequences, both LE-ACS3 and AtACS5 are categorized as type 2 isozymes and possess a consensus C-terminal sequence. In contrast, LE-ACS2 and LE-ACS4 are type 1 and type 3 isozymes, respectively, both of which do not possess this specific C-terminal sequence. Yeast two-hybrid analysis using chimeric constructs between LE-ACS2 and LE-ACS3 revealed that the type-2-ACS-specific C-terminal tail is required for interaction with ETO1. When treated with auxin to induce LE-ACS3, seedlings of ETO1-OE produced less ethylene than the wild type, despite comparable expression of the LE-ACS3 gene in the wild type. Conclusion These results suggest that ETO1